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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. Vacuum investment cast PH13-8Mo corrosion resistant steel. (SAE standard)

    SciTech Connect

    1991-07-01

    An industry-wide interest has arisen with regards to the properties and capabilities of investment cast PH 13-8Mo corrosion resistant steel. Specifically of interest are the structural applications in the aerospace industry for this product heat treated to the H1000 condition. The objective of this AMEC cooperative test program was to generate and compile useful data for aerospace structural evaluation of investment cast PH 13-8Mo heat treated to H1000. The determination was made of overall mechanical properties, fatigue, fracture toughness, and crack growth data along with basic microstructural evaluation of the investment cast material. The evaluation of mechanical property variations between cast and machined tensile specimens and evaluation of microstructural constituents. PH 13-8Mo, H1000 investment castings for use in the aerospace industry is included.

  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. On yield loci of HY80, HY100 steels and Ti-6Al-2Nb-1Ta-0. 8Mo

    SciTech Connect

    Chan, K.S.; Lindholm, U.S.; Wise, J.

    1984-11-01

    This paper extends other findings by examining the biaxial yield behavior of Ti-6A1-1Nb-1Ta-0.8Mo and HY 100 steel. The results of the study are compared with previous findings of HY80 steel to assess the effect of crystallography on the shape of the yield surface.

  5. 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.

  6. 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.

  7. SD46 Facilities and Capabilities

    NASA Technical Reports Server (NTRS)

    Ramachandran, N.; Curreri, Peter A. (Technical Monitor)

    2002-01-01

    The displays for the Materials Conference presents some of the facilities and capabilities in SD46 that can be useful to a prospective researcher from University, Academia or other government labs. Several of these already have associated personnel as principal and co-investigators on NASA peer reviewed science investigations. 1. SCN purification facility 2. ESL facility 3. Static and Dynamic magnetic field facility 4. Microanalysis facility 5. MSG Investigation - PFMI 6. Thermo physical Properties Measurement Capabilities.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. Bulk deformation of Ti-6.8Mo-4.5Fe-1.5Al (timetal LCB) alloy

    NASA Astrophysics Data System (ADS)

    Weiss, I.; Srinivasan, R.; Saqib, M.; Stefansson, N.; Jackson, A. G.; Leclair, S. R.

    1996-06-01

    Recently, a low-cost near-β titanium alloy (Timetal LCB Ti-6.8Mo-4.5Fe-l.5Al wt %) containing iron and molybdenum has been developed. This alloy is cold formable in the β microstructure and can be aged to high strengths by precipitating the a phase. Due to its combination of cold formability and high strength, the alloy is a potential replacement for steel components in the automotive industry. The current study was undertaken to evaluate the cold bulk forming characteristics of Timetal LCB for use in lightweight automotive applications. Room-temperature compression tests conducted over a strain-rate range of 0.01 to 5/s indicate that the bulk cold compression of the alloy is affected by two factors: the microstructure and the length-to-diameter aspect ratio of the specimen. In the aged condition, when the microstructure has a-phase particles distributed along flow lines in the β-phase matrix, the alloy has the propensity for shear failure when deformed in compression in a direction parallel to the flow lines. In the solution-heat-treated condition, the microstructure consists of β grains with athermal ω phase. In this condition, the alloy can be cold compressed to 75 % reduction in height using specimens with aspect ratio of 1.125, but fails by shear for a larger aspect ratio of 1.5. Plastic deformation of the material occurs initially by single slip in most grains, but changes to multiple slip at true plastic strains larger than about 0.15. At a slow strain rate, the deformation is uniform, and the material work hardens continuously. At high strain rates, shear bands develop, and the localized deformation and temperature rise due to deformation heating leads to flow softening during compression. Although there is a considerable rise in temperature (200 to 500 °) during deformation, precipitation of the a phase was not observed.

  15. 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.

  16. 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.

  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. The SD oscillator and its attractors

    NASA Astrophysics Data System (ADS)

    Cao, Q.; Wiercigroch, M.; Pavlovskaia, E.; Grebogi, C.; Michael, J.; Thompson, T.

    2008-02-01

    We propose a new archetypal oscillator for smooth and discontinuous systems (SD oscillator). This oscillator behaves both smooth and discontinuous system depending on the value of the smoothness parameter. New dynamic behaviour is presented for the transitions from the smooth to discontinuous regime.

  19. NDPC-SD Data Probes Worksheet

    ERIC Educational Resources Information Center

    National Dropout Prevention Center for Students with Disabilities, 2011

    2011-01-01

    This worksheet from the National Dropout Prevention Center for Students with Disabilities (NDPC-SD) is an optional tool to help schools organize multiple years of student and program data for the purpose of identifying school-completion needs that can be addressed through the implementation of research-based interventions. It is designed for use…

  20. 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.

  1. Plane Shock Generator Explosive Lens: Shock characterization of 4340 and PH13-8Mo steels, C360 brass and PZT 65/35 ferro-electric ceramic

    SciTech Connect

    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.

  2. 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.

  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. Understanding nuclei in the upper sd - shell

    SciTech Connect

    Sarkar, M. Saha; Bisoi, Abhijit; Ray, Sudatta; Kshetri, Ritesh; Sarkar, S.

    2014-08-14

    Nuclei in the upper-sd shell usually exhibit characteristics of spherical single particle excitations. In the recent years, employment of sophisticated techniques of gamma spectroscopy has led to observation of high spin states of several nuclei near A ≃ 40. In a few of them multiparticle, multihole rotational states coexist with states of single particle nature. We have studied a few nuclei in this mass region experimentally, using various campaigns of the Indian National Gamma Array setup. We have compared and combined our empirical observations with the large-scale shell model results to interpret the structure of these nuclei. Indication of population of states of large deformation has been found in our data. This gives us an opportunity to investigate the interplay of single particle and collective degrees of freedom in this mass region.

  5. 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.

  6. 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

  7. 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

  8. Antipsychotic Drugs Inhibit Platelet Aggregation via P2Y1 and P2Y12 Receptors

    PubMed Central

    Wu, Chang-Chieh; Tsai, Fu-Ming; Chen, Mao-Liang; Wu, Semon; Lee, Ming-Cheng; Tsai, Tzung-Chieh; Wang, Lu-Kai; Wang, Chun-Hua

    2016-01-01

    Antipsychotic drugs (APDs) used to treat clinical psychotic syndromes cause a variety of blood dyscrasias. APDs suppress the aggregation of platelets; however, the underlying mechanism remains unknown. We first analyzed platelet aggregation and clot formation in platelets treated with APDs, risperidone, clozapine, or haloperidol, using an aggregometer and rotational thromboelastometry (ROTEM). Our data indicated that platelet aggregation was inhibited, that clot formation time was increased, and that clot firmness was decreased in platelets pretreated with APDs. We also examined the role two major adenosine diphosphate (ADP) receptors, P2Y1 and P2Y12, play in ADP-mediated platelet activation and APD-mediated suppression of platelet aggregation. Our results show that P2Y1 receptor stimulation with ADP-induced calcium influx was inhibited by APDs in human and rats' platelets, as assessed by in vitro or ex vivo approach, respectively. In contrast, APDs, risperidone and clozapine, alleviated P2Y12-mediated cAMP suppression, and the release of thromboxane A2 and arachidonic acid by activated platelets decreased after APD treatment in human and rats' platelets. Our data demonstrate that each APD tested significantly suppressed platelet aggregation via different mechanisms. PMID:27069920

  9. Syntheses, structures and properties of two new organic-inorganic hybrid materials based on ε-Zn Keggin units {ε-PMo(V)8Mo(VI)4O(40-x)(OH)(x)Zn4}.

    PubMed

    Miao, Hao; Hu, Gonghao; Guo, Jiuyu; Wan, Hongxiang; Mei, Hua; Zhang, Yu; Xu, Yan

    2015-01-14

    Two novel organic-inorganic hybrids, Na[PMo(V)8Mo(VI)4O38(OH)2Zn4][pyim]2·1.5H2O [ε(pyim)2] (pyim = 2-(2-pyridyl)-imidazole) and [PMo(V)8Mo(VI)4O37(OH)3Zn4]2[pyim]6·4H2O [ε2(pyim)6], based on ε-Zn Keggin units {ε-PMo(V)8Mo(VI)4O(40-x)(OH)(x)Zn4}, have been successfully synthesized under hydrothermal conditions by controlling the pH values. Structural analysis indicates that the framework of ε(pyim)2 is a 1D chain constructed by monomeric ε-Zn units modified by pyim ligands, while ε2(pyim)6 is an isolated structural compound with dimeric ε-Zn units modified by pyim ligands. This is the first isolated structure of the ε-Keggin POMs system. The luminescent and electrochemical properties of ε(pyim)2 and ε2(pyim)6 were investigated. ε2(pyim)6 also shows high catalytic activity for the esterification of phosphoric acid with equimolar lauryl alcohol to monoalkyl phosphate ester (MAP). PMID:25387358

  10. 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

  11. Molecular mechanisms of platelet P2Y(12) receptor regulation.

    PubMed

    Cunningham, Margaret R; Nisar, Shaista P; Mundell, Stuart J

    2013-02-01

    Platelets are critical for haemostasis, however inappropriate activation can lead to the development of arterial thrombosis, which can result in heart attack and stroke. ADP is a key platelet agonist that exerts its actions via stimulation of two surface GPCRs (G-protein-coupled receptors), P2Y(1) and P2Y(12). Similar to most GPCRs, P2Y receptor activity is tightly regulated by a number of complex mechanisms including receptor desensitization, internalization and recycling. In the present article, we review the molecular mechanisms that underlie P2Y(1) and P2Y(12) receptor regulation, with particular emphasis on the structural motifs within the P2Y(12) receptor, which are required to maintain regulatory protein interaction. The implications of these findings for platelet responsiveness are also discussed. PMID:23356287

  12. P2Y1 and P2Y12 receptors for ADP desensitize by distinct kinase-dependent mechanisms.

    PubMed

    Hardy, Adam R; Conley, Pamela B; Luo, Jiansong; Benovic, Jeffrey L; Poole, Alastair W; Mundell, Stuart J

    2005-05-01

    Adenosine 5'-diphosphate (ADP) plays a central role in regulating platelet function by the activation of the G protein-coupled receptors P2Y(1) and P2Y(12). Although it is well established that aggregation responses of platelets to ADP desensitize, the underlying mechanisms involved remain unclear. In this study we demonstrate that P2Y(1)- and P2Y(12)-mediated platelet responses desensitize rapidly. Furthermore, we have established that these receptors desensitize by different kinase-dependent mechanisms. G protein-coupled receptor kinase (GRK) 2 and GRK6 are both endogenously expressed in platelets. Transient overexpression of dominant-negative mutants of these kinases or reductions in endogenous GRK expression by the use of specific siRNAs in 1321N1 cells showed that P2Y(12), but not P2Y(1), desensitization is mediated by GRKs. In contrast, desensitization of P2Y(1), but not P2Y(12), is largely dependent on protein kinase C activity. This study is the first to show that both P2Y(1) and P2Y(12) desensitize in human platelets, and it reveals ways in which their sensitivity to ADP may be differentially and independently altered. PMID:15665114

  13. 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…

  14. 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…

  15. 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.

  16. Substellar objects around the sdB eclipsing Binaries

    NASA Astrophysics Data System (ADS)

    Zhu, Liying; Qian, Shengbang; Liao, Wenping; Zhao, Ergang; Li, Linjia

    2016-07-01

    The sdB-type eclipsing binary consists a very hot subdwarf B (sdB) type primary and a low mass secondary with short period. They are detached binaries and show very narrow eclipse profiles, which benefits the determination of the precise eclipse times. With the precise times of light minimum, we can detected small mass objects around them by analyzing the observed-calculated (O-C) curve based on the light time effect. For searching the substellar objects orbiting around the binaries, we have monitored sdB-type eclipsing binaries for decades. A group of brown dwarfs and planets have been detected since then. In the present paper, we focus on the target NSVS07826147, which may be another exoplanet host candidate among the group of the sdB-type eclipsing binaries.

  17. Photometric Survey to Search for Field sdO Pulsators

    NASA Astrophysics Data System (ADS)

    Johnson, C.; Green, E.; Wallace, S.; O'Malley, C.; Amaya, H.; Biddle, L.; Fontaine, G.

    2014-04-01

    We present the results of a campaign to search for subdwarf O (sdO) star pulsators among bright field stars. The motivation for this project is the recent discovery by Randall et al. (2011) of four rapidly pulsating sdO stars in the globular cluster ω Cen, with Teff near 50,000 K, 5.4 < log g < 6.0, and hydrogen-rich atmospheres. The only previously known sdO pulsator is significantly hotter at 68,500 K and log g = 6.1. All of the sdO pulsators identified so far are fainter than V≍17.4 and, thus, are poor candidates for an in-depth follow-up with asteroseismology. We therefore obtained high S/N light curves and spectroscopy for a number of field sdO stars to attempt to discover bright counterparts to these stars, particularly the ω Cen pulsators. Our primary sample consisted of 19 sdO stars with hydrogen-rich atmospheres, log N(He)/N(H) < -1.0, effective temperatures in the range 40,000 K < Teff < 67,000 K, and surface gravities 5.3 < log g < 6.1. We also observed 17 additional helium-rich sdO stars with log N(He)/N(H) > -0.1 and similar temperatures and gravities. To date, we have found no detectable pulsations at amplitudes above 0.08% (4 times the mean noise level) in any of the 36 field sdO stars that we observed. The presence of pulsations in ω Cen sdO stars and their apparent absence in seemingly comparable field sdO stars is perplexing. While very suggestive, the significance of this result is difficult to assess more completely right now due to remaining uncertainties about the temperature width and purity of the ω Cen instability strip and the existence of any sdO pulsators with weaker amplitudes than the current detection limit in globular clusters.

  18. Composite particle representation for light sd shell nuclei

    SciTech Connect

    Collinson, D.F.

    1986-01-01

    The Composite Particle Representation is applied to light sd shell nuclei /sup 20/O, /sup 20/F and /sup 20/Ne. The energy spectrum is found to agree exactly with the shell model in all cases. The CPR theory is then used to examine the possible boson structure of sd shell wavefunctions. Only in the case of /sup 20/O are the wavefunctions found to have a high boson probability.

  19. Purification, Characterization, and Optimum Conditions of Fermencin SD11, a Bacteriocin Produced by Human Orally Lactobacillus fermentum SD11.

    PubMed

    Wannun, Phirawat; Piwat, Supatcharin; Teanpaisan, Rawee

    2016-06-01

    Fermencin SD11, a bacteriocin produced by human orally Lactobacillus fermentum SD11, was purified, characterized, and optimized in conditions for bacterial growth and bacteriocin production. Fermencin SD11 was purified using three steps of ammonium sulfate precipitation, gel filtration chromatography, and reverse-phase high-performance liquid chromatography. The molecular weight was found to be 33,000 Da using SDS-PAGE and confirmed as 33,593.4 Da by liquid chromatography-mass spectrometry. Fermencin SD11 exhibited activity against a wide range of oral pathogens including cariogenic and periodontogenic pathogens and Candida. The active activity was stable between 60 - 80 °C in a pH range of 3.0 to 7.0. It was sensitive to proteolytic enzymes (proteinase K and trypsin), but it was not affected by α-amylase, catalase, lysozyme, and saliva. The optimum conditions for growth and bacteriocin production of L. fermentum SD11 were cultured at acidic with pH of 5.0-6.0 at 37 or 40 °C under aerobic or anaerobic conditions for 12 h. It is promising that L. fermentum SD11 and its bacteriocin may be an alternative approach for promoting oral health or prevention of oral diseases, e.g., dental caries and periodontitis, which would require further clinical trials. PMID:26892008

  20. Microwave Spectrum of the SD+3 Ion: Molecular Structure.

    PubMed

    Araki; Ozeki; Saito

    1998-11-01

    The J = 1-0 to 4-3 spectral lines of SD+3 were measured in the 152-610 GHz region using a source-modulated microwave spectrometer. The SD+3 ion was generated in a free space absorption cell by a hollow-cathode discharge in a gas mixture of D2S and D2. The rotational constant B0 and the centrifugal distortion constants DJ and DJK were determined from the measured frequencies. A vibration-rotation analysis was carried out and the rz structures of SH+3 and SD+3 were derived from their zero point averaged rotational constants, expressed as SH+3: rz = 1.36512(22) Å and thetaz = 94.098(26) degrees, and SD+3: rz = 1.36086(16) Å and thetaz = 94.1211(195) degrees, where the difference between thetaz(HSH) and thetaz(DSD) was assumed to be the same as that between thetaz(HPH) of PH3 and thetaz(DPD) of PD3. From the shift between the rz structures of SH+3 and SD+3, the re structure of SH+3 was estimated to be re = 1.35001(113) Å, thetae = 94.181(135) degrees. Copyright 1998 Academic Press. PMID:9770407

  1. 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.

  2. 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. PMID:20843716

  3. 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...

  4. 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,...

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

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-20

    ... From the Federal Register Online via the Government Publishing Office U.S. SMALL BUSINESS ADMINISTRATION South Dakota Disaster Number SD-00041 AGENCY: U.S. Small Business Administration. ACTION... 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

    ... From the Federal Register Online via the Government Publishing Office U.S. SMALL BUSINESS ADMINISTRATION South Dakota Disaster Number SD-00041 AGENCY: U.S. Small Business Administration. ACTION... completed loan applications to: U.S. Small Business Administration, Processing and Disbursement...

  7. 78 FR 29425 - South Dakota Disaster #SD-00057

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-20

    ... From the Federal Register Online via the Government Publishing Office SMALL BUSINESS ADMINISTRATION South Dakota Disaster SD-00057 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY... State of South Dakota (FEMA-4115-DR), dated 05/10/2013. Incident: Severe Winter Storm and...

  8. 76 FR 40767 - South Dakota Disaster Number SD-00041

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-11

    ... ADMINISTRATION South Dakota Disaster Number SD-00041 AGENCY: U.S. Small Business Administration. ACTION... Assistance Only for the State of South Dakota (FEMA-1984-DR), dated 05/13/2011. Incident: Flooding. Incident... Non-Profit organizations in the State of South Dakota, dated 05/13/2011, is hereby amended to...

  9. 75 FR 19435 - South Dakota Disaster Number SD-00027

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-14

    ... ADMINISTRATION South Dakota Disaster Number SD-00027 AGENCY: Small Business Administration. ACTION: Amendment 1... Only for the State of South Dakota (FEMA-1886-DR), dated 03/09/2010. Incident: Severe Winter Storm and... State of South Dakota, dated 03/09/2010, is hereby amended to include the following areas as...

  10. 75 FR 13145 - SOUTH DAKOTA Disaster #SD-00027

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-18

    ... From the Federal Register Online via the Government Publishing Office SMALL BUSINESS ADMINISTRATION SOUTH DAKOTA Disaster SD-00027 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY... State of South Dakota (FEMA-1886-DR), dated 03/09/2010. Incident: Severe Winter Storm and...

  11. 76 FR 54520 - South Dakota Disaster #SD-00042

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-01

    ... ADMINISTRATION South Dakota Disaster SD-00042 AGENCY: U.S. Small Business Administration. ACTION: Notice. ] SUMMARY: This is a Notice of the Presidential declaration of a major disaster for the State of South... Injury Loans Only): South Dakota: Aurora, Bon Homme, Brule, Clay, Dewey, Douglas, Gregory,...

  12. 75 FR 39994 - South Dakota Disaster Number SD-00031

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-13

    ... ADMINISTRATION South Dakota Disaster Number SD-00031 AGENCY: U.S. Small Business Administration. ACTION... Assistance Only for the State of South Dakota (FEMA-1915-DR), dated 05/13/2010. Incident: Flooding. Incident... Non-Profit organizations in the State of South Dakota, dated 05/13/2010, is hereby amended to...

  13. 75 FR 28311 - South Dakota Disaster # SD-00031

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-20

    ... From the Federal Register Online via the Government Publishing Office SMALL BUSINESS ADMINISTRATION South Dakota Disaster SD-00031 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY... State of South Dakota (FEMA--1915--DR), dated 05/13/2010. Incident: Flooding. Incident Period:...

  14. 75 FR 61229 - South Dakota Disaster #SD-00034

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-04

    ... From the Federal Register Online via the Government Publishing Office SMALL BUSINESS ADMINISTRATION South Dakota Disaster SD-00034 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY... State of South Dakota (FEMA-1938-DR), dated 09/23/2010. Incident: Severe Storms and Flooding....

  15. 76 FR 30226 - South Dakota Disaster # SD-00041

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-24

    ... From the Federal Register Online via the Government Publishing Office SMALL BUSINESS ADMINISTRATION South Dakota Disaster SD-00041 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY... State of South Dakota (FEMA-1984-DR), dated 05/13/2011. Incident: Flooding. Incident Period:...

  16. 75 FR 30873 - South Dakota Disaster Number SD-00031

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-02

    ... ADMINISTRATION South Dakota Disaster Number SD-00031 AGENCY: U.S. Small Business Administration. ACTION... Assistance Only for the State of South Dakota (FEMA-1915-DR), dated 05/13/2010. Incident: Flooding. Incident... Non-Profit organizations in the State of South Dakota, dated 05/13/2010, is hereby amended to...

  17. 75 FR 38154 - South Dakota Disaster Number SD-00031

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-01

    ... ADMINISTRATION South Dakota Disaster Number SD-00031 AGENCY: U.S. Small Business Administration. ACTION... Assistance Only for the State of SOUTH DAKOTA (FEMA-1915-DR), dated 05/13/2010. Incident: Flooding. Incident... Non-Profit organizations in the State of SOUTH DAKOTA, dated 05/13/2010, is hereby amended...

  18. 75 FR 28312 - South Dakota Disaster # SD-00030

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-20

    ... From the Federal Register Online via the Government Publishing Office SMALL BUSINESS ADMINISTRATION South Dakota Disaster SD-00030 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY... State of South Dakota (FEMA-1914-DR), dated 05/13/2010. Incident: Severe Winter Storm. Incident...

  19. 75 FR 47035 - South Dakota Disaster #SD-00033

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-04

    ... From the Federal Register Online via the Government Publishing Office SMALL BUSINESS ADMINISTRATION South Dakota Disaster SD-00033 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY... State of South Dakota (FEMA-1929-DR), dated 07/29/2010. Incident: Severe storms, tornadoes, and...

  20. 75 FR 69732 - South Dakota Disaster #SD-00035

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-15

    ... From the Federal Register Online via the Government Publishing Office SMALL BUSINESS ADMINISTRATION South Dakota Disaster SD-00035 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY... State of South Dakota (FEMA-1947-DR), dated 11/02/2010. Incident: Severe Storms and Flooding....

  1. 77 FR 46284 - Amendment of Class E Airspace; Lemmon, SD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-03

    ...: Authority: 49 U.S.C. 106(g), 40103, 40113, 40120; E. O. 10854, 24 FR 9565, 3 CFR, 1959-1963 Comp., p. 389... 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...

  2. 76 FR 40597 - Amendment of Class E Airspace; Madison, SD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-11

    ...), 40103, 40113, 40120; E.O. 10854, 24 FR 9565, 3 CFR, 1959-1963 Comp., p. 389. Sec. 71.1 0 2. The... Federal Aviation Administration 14 CFR Part 71 Amendment of Class E Airspace; Madison, SD AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: This action amends Class E airspace...

  3. 78 FR 41837 - Establishment of Class E Airspace; Parkston, SD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-12

    ..., 40113, 40120; E.O. 10854, 24 FR 9565, 3 CFR, 1959-1963 Comp., p. 389. Sec. 71.1 0 2. The incorporation... Federal Aviation Administration 14 CFR Part 71 Establishment of Class E Airspace; Parkston, SD AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: This action establishes Class...

  4. 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...

  5. 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

  6. Carbon abundances of sdO stars from SPY

    NASA Astrophysics Data System (ADS)

    Hirsch, Heiko; Heber, Uli

    2009-06-01

    Ströer et al. (2007) recently suggested a classification of sdOs according to supersolar and subsolar helium abundances, with only the helium-enriched stars showing signes of carbon and/or nitrogen in their optical spectra. We aim to derive reliable carbon and nitrogen abundances by fitting synthetic spectra to data obtained with the UVES spectrograph at ESO. Here we present our first results of the analysis of carbon abundances in hot subdwarf O stars. By constructing a grid of model atmospheres consisting of hydrogen, helium and carbon we were able to derive atmospheric parameters of nine carbon rich sdOs. We find log(NC/Ntotal) up to ten times higher than the solar value, while the mean value for the effective temperature and the surface gravity is slightly lower than derived by helium-hydrogen models only. Surprisingly, we also find three fast rotators among our program stars.

  7. 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.

  8. Gray-shading for the SD-4060 graphics device

    NASA Technical Reports Server (NTRS)

    Gloeckler, C.

    1975-01-01

    Grays, a FORTRAN program, is described which will generate gray shading for the SD-4060 graphics device. The program produces 10 shades of gray ranging from no shading at all to complete coverage of the film frame. The graphing capabilities are summarized and illustrated. The figures displayed are representative of the microfilm output, but the distinction between various intensities is much clearer on the film, especially at the more intense shading.

  9. Sex differences in the stress response in SD rats.

    PubMed

    Lu, Jing; Wu, Xue-Yan; Zhu, Qiong-Bin; Li, Jia; Shi, Li-Gen; Wu, Juan-Li; Zhang, Qi-Jun; Huang, Man-Li; Bao, Ai-Min

    2015-05-01

    Sex differences play an important role in depression, the basis of which is an excessive stress response. We aimed at revealing the neurobiological sex differences in the same study in acute- and chronically-stressed rats. Female Sprague-Dawley (SD) rats were randomly divided into 6 groups: chronic unpredictable mild stress (CUMS), acute foot shock (FS) and controls, animals in all 3 groups were sacrificed in proestrus or diestrus. Male SD rats were randomly divided into 3 groups: CUMS, FS and controls. Comparisons were made of behavioral changes in CUMS and control rats, plasma levels of corticosterone (CORT), testosterone (T) and estradiol (E2), and of the hypothalamic mRNA-expression of stress-related molecules, i.e. estrogen receptor α and β, androgen receptor, aromatase, mineralocorticoid receptor, glucocorticoid receptor, corticotropin-releasing hormone, arginine vasopressin and oxytocin. CUMS resulted in disordered estrus cycles, more behavioral and hypothalamic stress-related molecules changes and a stronger CORT response in female rats compared with male rats. Female rats also showed decreased E2 and T levels after FS and CUMS, while male FS rats showed increased E2 and male CUMS rats showed decreased T levels. Stress affects the behavioral, endocrine and the molecular response of the stress systems in the hypothalamus of SD rats in a clear sexual dimorphic way, which has parallels in human data on stress and depression. PMID:25687843

  10. Characteristics of new P2Y12 inhibitors: selection of P2Y12 inhibitors in clinical practice.

    PubMed

    Golino, Paolo

    2013-12-01

    The options for antithrombotic therapy have recently been expanded, facilitating optimal tailored treatment. Dual antiplatelet therapy with aspirin and an approved adenosine diphosphate P2Y12 receptor antagonist is recommended for the management of patients with acute coronary syndromes (ACS). However, there are a number of controversies: which P2Y12 inhibitor to choose; how long should antiplatelet therapy be used so as to prevent thrombotic events and minimize bleeding risks; whether to use drug-eluting (DES) or bare-metal stents (BMS) and how to manage the individual variability in response to clopidogrel. Clopidogrel in combination with aspirin has been the standard dual antiplatelet regimen for ACS. The new, more potent P2Y12 inhibitors, prasugrel and ticagrelor, have shown improved antithrombotic effects compared with clopidogrel in patients with ACS (with or without ST-segment elevation myocardial infarction) in landmark trials, even if they were associated with an increased risk of major bleeding. Different pharmacogenetic and pharmacodynamic characteristics may explain, in part, the different pharmacologic and clinical responses to these antiplatelet agents. Importantly, both clopidogrel and prasugrel are prodrugs, i.e., they need to be converted in vivo into active metabolites that selectively and irreversibly bind the P2Y12 receptor. Unlike clopidogrel, however, common functional cytochrome P450 genetic variants do not affect prasugrel active metabolite levels or inhibition of platelet aggregation. In contrast, ticagrelor is not a prodrug (i.e., does not require hepatic metabolism to exert its antiplatelet effect) and represents the first oral P2Y12 receptor antagonist that is reversibly bound. Similar to prasugrel, ticagrelor achieves greater and more rapid inhibition of platelet function than clopidogrel. Evidence suggests that the new P2Y12 antagonists may offer improved antithrombotic effects compared with clopidogrel in selected patients for the

  11. Residual platelet ADP reactivity after clopidogrel treatment is dependent on activation of both the unblocked P2Y1 and the P2Y12 receptor and is correlated with protein expression of P2Y12

    PubMed Central

    Braun, Oscar Ö; Amisten, Stefan; Wihlborg, Anna-Karin; Hunting, Karen; Nilsson, David

    2006-01-01

    Two ADP receptors have been identified on human platelets: P2Y1 and P2Y12. The P2Y12 receptor blocker clopidogrel is widely used to reduce the risks in acute coronary syndromes, but, currently, there is no P2Y1 blocker in clinical use. Evidence for variable responses to clopidogrel has been described in several reports. The mechanistic explanation for this phenomenon is not fully understood. The aim of this study was to examine mechanisms responsible for variability of 2MeS-ADP, a stable ADP analogue, induced platelet reactivity in clopidogrel-treated patients. Platelet reactivity was assessed by flow cytometry measurements of P-selectin (CD62P) and activated GpIIb/IIIa complex (PAC-1). Residual 2MeS-ADP activation via the P2Y12 and P2Y1 receptors was determined by co-incubation with the selective antagonists AR-C69931 and MRS2179 in vitro. P2Y1 and P2Y12 receptor expression on both RNA and protein level were determined, as well as the P2Y12 H1 or H2 haplotypes. Our data suggest that the residual platelet activation of 2MeS-ADP after clopidogrel treatment is partly due to an inadequate antagonistic effect of clopidogrel on the P2Y12 receptor and partly due to activation of the P2Y1 receptor, which is unaffected by clopidogrel. Moreover, a correlation between increased P2Y12 protein expression on platelets and decreased response to clopidogrel was noticed, r2=0.43 (P<0.05). No correlation was found between P2Y12 mRNA levels and clopidogrel resistance, indicating post-transcriptional mechanisms. To achieve additional ADP inhibition in platelets, antagonists directed at the P2Y1 receptor could be more promising than the development of more potent P2Y12 receptor antagonists. PMID:18404433

  12. The Molecular Mechanism of P2Y1 Receptor Activation.

    PubMed

    Yuan, Shuguang; Chan, H C Stephen; Vogel, Horst; Filipek, Slawomir; Stevens, Raymond C; Palczewski, Krzysztof

    2016-08-22

    Human purinergic G protein-coupled receptor P2Y1 (P2Y1 R) is activated by adenosine 5'-diphosphate (ADP) to induce platelet activation and thereby serves as an important antithrombotic drug target. Crystal structures of P2Y1 R revealed that one ligand (MRS2500) binds to the extracellular vestibule of this GPCR, whereas another (BPTU) occupies the surface between transmembrane (TM) helices TM2 and TM3. We introduced a total of 20 μs all-atom long-timescale molecular dynamic (MD) simulations to inquire why two molecules in completely different locations both serve as antagonists while ADP activates the receptor. Our results indicate that BPTU acts as an antagonist by stabilizing extracellular helix bundles leading to an increase of the lipid order, whereas MRS2500 blocks signaling by occupying the ligand binding site. Both antagonists stabilize an ionic lock within the receptor. However, binding of ADP breaks this ionic lock, forming a continuous water channel that leads to P2Y1 R activation. PMID:27460867

  13. The Molecular Mechanism of P2Y1 Receptor Activation

    PubMed Central

    Chan, H. C. Stephen; Vogel, Horst; Filipek, Slawomir

    2016-01-01

    Human purinergic G protein-coupled receptor P2Y1 (P2Y1R) is activated by adenosine 5’-diphosphate (ADP) to induce platelet activation and thereby serves as an important antithrombotic drug target. Crystal structures of P2Y1R revealed that one ligand (MRS2500) binds to the extracellular vestibule of this GPCR, whereas another (BPTU) occupies the surface between transmembrane (TM) helices TM2 and TM3. We introduced a total of 20 µs all-atom long-timescale molecular dynamic (MD) simulations to inquire why two molecules in completely different locations both serve as antagonists while ADP activates the receptor. Our results indicate that BPTU acts as an antagonist by stabilizing extracellular helix bundles leading to an increase of the lipid order, whereas MRS2500 blocks signaling by occupying the ligand binding site. Both antagonists stabilize an ionic lock within the receptor. However, binding of ADP breaks this ionic lock, forming a continuous water channel that leads to P2Y1R activation. PMID:27460867

  14. 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

  15. Automated Drusen Segmentation and Quantification in SD-OCT Images

    PubMed Central

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

    2013-01-01

    Spectral domain optical coherence tomography (SD-OCT) is a useful tool for the visualization of drusen, a retinal abnormality seen in patients with age-related macular degeneration (AMD); however, objective assessment of drusen is thwarted by the lack of a method to robustly quantify these lesions on serial OCT images. Here, we describe an automatic drusen segmentation method for SD-OCT retinal images, which leverages a priori knowledge of normal retinal morphology and anatomical features. The highly reflective and locally connected pixels located below the retinal nerve fiber layer (RNFL) are used to generate a segmentation of the retinal pigment epithelium (RPE) layer. The observed and expected contours of the RPE layer are obtained by interpolating and fitting the shape of the segmented RPE layer, respectively. The areas located between the interpolated and fitted RPE shapes (which have nonzero area when drusen occurs) are marked as drusen. To enhance drusen quantification, we also developed a novel method of retinal projection to generate an en face retinal image based on the RPE extraction, which improves the quality of drusen visualization over the current approach to producing retinal projections from SD-OCT images based on a summed-voxel projection (SVP), and it provides a means of obtaining quantitative features of drusen in the en face projection. Visualization of the segmented drusen is refined through several post-processing steps, drusen detection to eliminate false positive detections on consecutive slices, drusen refinement on a projection view of drusen, and drusen smoothing. Experimental evaluation results demonstrate that our method is effective for drusen segmentation. In a preliminary analysis of the potential clinical utility of our methods, quantitative drusen measurements, such as area and volume, can be correlated with the drusen progression in non-exudative AMD, suggesting that our approach may produce useful quantitative imaging biomarkers

  16. Reciprocal cross-talk between P2Y1 and P2Y12 receptors at the level of calcium signaling in human platelets.

    PubMed

    Hardy, Adam R; Jones, Matthew L; Mundell, Stuart J; Poole, Alastair W

    2004-09-15

    Adenosine diphosphate (ADP), an important platelet agonist, acts through 2 G-protein-coupled receptors (GPCRs), P2Y(1) and P2Y(12), which signal through Gq and Gi, respectively. There is increasing evidence for cross-talk between signaling pathways downstream of GPCRs and here we demonstrate cross-talk between these 2 ADP receptors in human platelets. We show that P2Y(12) contributes to platelet signaling by potentiating the P2Y(1)-induced calcium response. This potentiation is mediated by 2 mechanisms: inhibition of adenylate cyclase and activation of phosphatidylinositol 3 (PI 3)-kinase. Furthermore, the Src family kinase inhibitor PP1 selectively potentiates the contribution to the calcium response by P2Y(12), although inhibition of adenylate cyclase by P2Y(12) is unaffected. Using PP1 in combination with the inhibitor of PI 3-kinase LY294002, we show that Src negatively regulates the PI 3-kinase-mediated component of the P2Y(12) calcium response. Finally, we were able to show that Src kinase is activated through P2Y(1) but not P2Y(12). Taken together, we present evidence for a complex signaling interplay between P2Y(1) and P2Y(12), where P2Y(12) is able to positively regulate P2Y(1) action and P2Y(1) negatively regulates this action of P2Y(12). It is likely that this interplay between receptors plays an important role in maintaining the delicate balance between platelet activation and inhibition during normal hemostasis. PMID:15187029

  17. Semantic description of drama scene by using SD-form

    NASA Astrophysics Data System (ADS)

    Niimi, Michiharu; Kawaguchi, Eiji

    1997-01-01

    Multimedia data processing is becoming more and more a central concern among the people who have been working on image processing. Multimedia database retrieval is one of such a problem. A foreign language study assisting system is a good example for a multimedia data base design. Because each language depends on conversational situation such as topic and speech intention as well as place of conversation.In that case, we can not neglect the semantic aspect of multimedia information. The author's group has already proposed a semantic structure description form, called the SD-form, of the language meaning. They studied the feasibility of its application to natural language generation, story understanding, and conversational text retrieval systems. This paper presents our new attempt to expand our previous system from a text database systems to a multimedia database system which include motion picture, speech sound as well as language text. the source of the data in this project is a series of bilingual TV drama broadcasted in Japan. The most important point is this attempt is that each video scene is described by a set of SD-forms by which scenes are retrieved semantically.

  18. FUSE Observations of He-rich sdB Stars

    NASA Technical Reports Server (NTRS)

    Swiegart, A. V.; Lanz, T.; Brown, T. M.; Hubeny, I.; Landsman, W. B.

    2003-01-01

    Most subdwarf B stars are extremely deficient in helium and selected light elements, but a minority are helium-rich. New evolutionary calculations suggest that these helium-rich sdB stars are the result of a delayed helium-core flash on the white dwarf cooling curve, which leads to extensive mixing between the hydrogen envelope and helium core. Such mixed stars should show greatly enhanced helium and carbon with respect to the other heavy elements. We have recently obtained FUSE spectra of two helium-rich sdB stars, PG1544+488 and JL87, revealing huge C Ill lines at 977 and 1176 A. Our analysis shows that PG1544+488 has a surface composition of 97% He, 2% C, and 1% N, in agreement with the new evolutionary scenario. While JL87 also reveals a large enrichment in carbon and nitrogen (1.4% and 0.4%, respectively), there is still a significant amount of hydrogen in its atmosphere.

  19. Digital LAMP in a sample self-digitization (SD) chip

    PubMed Central

    Herrick, Alison M.; Dimov, Ivan K.; Lee, Luke P.; Chiu, Daniel T.

    2012-01-01

    This paper describes the realization of digital loop-mediated DNA amplification (dLAMP) in a sample self-digitization (SD) chip. Digital DNA amplification has become an attractive technique to quantify absolute concentrations of DNA in a sample. While digital polymerase chain reaction is still the most widespread implementation, its use in resource—limited settings is impeded by the need for thermal cycling and robust temperature control. In such situations, isothermal protocols that can amplify DNA or RNA without thermal cycling are of great interest. Here, we showed the successful amplification of single DNA molecules in a stationary droplet array using isothermal digital loop-mediated DNA amplification. Unlike most (if not all) existing methods for sample discretization, our design allows for automated, loss-less digitization of sample volumes on-chip. We demonstrated accurate quantification of relative and absolute DNA concentrations with sample volumes of less than 2 μl. We assessed the homogeneity of droplet size during sample self-digitization in our device, and verified that the size variation was small enough such that straightforward counting of LAMP-active droplets sufficed for data analysis. We anticipate that the simplicity and robustness of our SD chip make it attractive as an inexpensive and easy-to-operate device for DNA amplification, for example in point-of-care settings. PMID:22399016

  20. Role of spinal P2Y6 and P2Y11 receptors in neuropathic pain in rats: possible involvement of glial cells

    PubMed Central

    2014-01-01

    Background The participation of spinal P2X receptors in neuropathic pain is well recognized. However, the role of P2Y receptors has been less studied. The purpose of this study was to investigate the contribution of spinal P2Y6,11 receptors following peripheral nerve damage induced by spinal nerve ligation. In addition, we determined the expression of P2Y6,11 receptors in the dorsal spinal cord in presence of the selective P2Y6,11 receptors antagonists. Furthermore, we evaluated the participation of spinal microglia and astrocytes in the pronociceptive role of P2Y6,11 receptors. Results Spinal administration of the selective P2Y6 (MRS2578, 10–100 μM) and P2Y11 (NF340, 0.3–30 μM) receptor antagonists reduced tactile allodynia in spinal nerve ligated rats. Nerve injury increased the expression of P2Y6,11 receptors at 7, 14 and 21 days after injury. Furthermore, intrathecal administration of MRS2578 (100 μM/day) and NF340 (30 μM/day) for 3 days significantly reduced spinal nerve injury-induced increase in P2Y6,11 receptors expression, respectively. Spinal treatment (on day 14 after injury) with minocycline (100 μg/day) or fluorocitrate (1 nmol/day) for 7 days reduced tactile allodynia and spinal nerve injury-induced up-regulation in Iba-1 and GFAP, respectively. In addition, minocycline reduced nerve injury-induced up-regulation in P2Y6,11 receptors whereas that fluorocitrate diminished P2Y11, but not P2Y6, receptors up-regulation. Intrathecal treatment (on day 21 after injury) with the selective P2Y6 (PSB0474, 3–30 μM) and P2Y11 (NF546, 1–10 μM) receptor agonists produced remarkable tactile allodynia in nerve ligated rats previously treated with minocycline or fluorocitrate for 7 days. Conclusions Our data suggest that spinal P2Y6 is present in spinal microglia while P2Y11 receptors are present in both spinal microglia and astrocytes, and both receptors are up-regulated in rats subjected to spinal nerve injury. In addition, our data suggest

  1. Open sd-shell nuclei from first principles

    DOE PAGESBeta

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

    2016-07-05

    We extend the ab initio coupled-cluster e ective 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 e ective eld theory evolved to a lower cuto via a similarity renormalization group transformation. We nd 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 e ectivemore » eld theory for deformed nuclei, thereby demonstrating that collective phenomena in sd-shell nuclei emerge from complex ab initio calculations.« less

  2. 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.

  3. Extracellular ATP inhibits chloride channels in mature mammalian skeletal muscle by activating P2Y1 receptors.

    PubMed

    Voss, Andrew A

    2009-12-01

    ATP is released from skeletal muscle during exercise, a discovery dating back to 1969. Surprisingly, few studies have examined the effects of extracellular ATP on mature mammalian skeletal muscle. This electrophysiological study examined the effects of extracellular ATP on fully innervated rat levator auris longus using two intracellular microelectrodes. The effects of ATP were determined by measuring the relative changes of miniature endplate potentials (mEPPs) and voltage responses to step current pulses in individual muscle fibres. Exposure to ATP (20 microm) prolonged the mEPP falling phase by 31 +/- 7.5% (values +/- s.d., n = 3 fibres). Concurrently, the input resistance increased by 31 +/- 2.0% and the time course of the voltage responses increased by 59 +/- 3.0%. Analogous effects were observed using 2 and 5 microm ATP, and on regions distal from the neuromuscular junction, indicating that physiologically relevant levels of ATP enhanced electrical signalling over the entire muscle fibre. The effects of extracellular ATP were blocked by 200 microm anthracene-9-carboxylic acid, a chloride channel inhibitor, and reduced concentrations of extracellular chloride, indicating that ATP inhibited chloride channels. A high affinity agonist for P2Y receptors, 2-methylthioadenosine-5-O-diphosphate (2MeSADP), induced similar effects to ATP with an EC(50) of 160 +/- 30 nm. The effects of 250 nm2MeSADP were blocked by 500 nmMRS2179, a specific P2Y(1) receptor inhibitor, suggesting that ATP acts on P2Y(1) receptors to inhibit chloride channels. The inhibition of chloride channels by extracellular ATP has implications for muscle excitability and fatigue, and the pathophysiology of myotonias. PMID:19805741

  4. Calmodulin interacts with the platelet ADP receptor P2Y1

    PubMed Central

    Arthur, Jane F.; Shen, Yang; Mu, Fi-Tjen; Leon, Catherine; Gachet, Christian; Berndt, Michael C.; Andrews, Robert K.

    2006-01-01

    P2Y1 [P2 (purinergic type-2)-receptor 1] is a G-protein-coupled ADP receptor that regulates platelet activation and ADP-induced Ca2+ signalling. Studies using P2Y1-knockout mice, Gq-deficient mice or P2Y1-selective inhibitors have previously identified a key role for P2Y1 in pathophysiological thrombus formation at high shear stress. We provide evidence that a positively charged juxtamembrane sequence within the cytoplasmic C-terminal tail of P2Y1 can bind directly to the cytosolic regulatory protein calmodulin. Deletion by mutagenesis of the calmodulin-binding domain of P2Y1 inhibits intracellular Ca2+ flux in transfected cells. These results suggest that the interaction of calmodulin with the P2Y1 C-terminal tail may regulate P2Y1-dependent platelet aggregation. PMID:16848759

  5. 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

  6. Chromosomal localization of the human P2y6 purinoceptor gene and phylogenetic analysis of the P2y purinoceptor family.

    PubMed

    Somers, G R; Hammet, F; Woollatt, E; Richards, R I; Southey, M C; Venter, D J

    1997-08-15

    The G-protein-coupled P2Y purinoceptors mediate a variety of physiological effects in response to extracellular nucleotides. With the recent discovery of several new members from a variety of species, the P2Y purinoceptor family now encompasses types P2Y1 to P2Y6. By fluorescence in situ hybridization and utilization of the National Center for Biotechnology Information (NCBI) database, the human P2Y6 gene was localized to chromosome 11q13.5, between polymorphic markers D11S1314 and D11S916. NCBI database analysis of the remaining human P2Y purinoceptor genes revealed that P2Y2 and P2Y6 mapped to within less than 4 cM, and thus constitute the first described chromosomal clustering of this gene family. Phylogenetic analysis of the P2Y purinoceptor family demonstrated the presence of five evolutionary branches and suggests the occurrence of an ancient gene duplication event. PMID:9286708

  7. Improved Hybrid Genome Assemblies of Two Strains of Bacteroides xylanisolvens, SD_CC_1b and SD_CC_2a, Obtained Using Illumina and 454 Sequencing Technologies

    PubMed Central

    Ramaraj, Thiruvarangan; Sundararajan, Anitha; Schilkey, Faye D.; DelVecchio, Vito G.; Donlon, Mildred; Ziemer, Cherie

    2014-01-01

    Bacteroides xlyanisolvens strains (SD_CC_1b, SD_CC_2a) isolated from human feces were grown on crystalline cellulose. Cellulolytic properties are not common in Bacteroides species. Here, we report improved genome sequences of both of the B. xlyanisolvens strains. PMID:24699955

  8. Improved hybrid genome assemblies of 2 strains of Bacteroides xylanisolvens SD-CC-1b and SD-CC-2a using Illumina and 454 sequencing technologies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bacteroides xlyanisolvens strains (SD_CC_1b, SD_CC_2a) isolated from human feces were able to grow on crystalline cellulose. Cellulolytic properties are not common in Bacteroides species. Here, we report improved genome sequences of both the B. xlyanisolvens strains....

  9. P2Y Receptors in Alzheimer’s Disease

    PubMed Central

    Erb, Laurie; Cao, Chen; Ajit, Deepa; Weisman, Gary A.

    2014-01-01

    Alzheimer’s disease (AD) is the most common cause of dementia, affecting more than 10% of people over the age of 65. Age is the greatest risk factor for AD, although a combination of genetic, lifestyle and environmental factors also contribute to disease development. Common features of AD are the formation of plaques composed of beta-amyloid peptides (Aβ) and neuronal death in brain regions involved in learning and memory. Although Aβ is neurotoxic, the primary mechanisms by which Aβ affects AD development remain uncertain and controversial. Mouse models overexpressing amyloid precursor protein and Aβ have revealed that Aβ has potent effects on neuroinflammation and cerebral blood flow that contribute to AD progression. Therefore, it is important to consider how endogenous signaling in the brain responds to Aβ and contributes to AD pathology. In recent years, Aβ has been shown to affect ATP release from brain and blood cells and alter the expression of G protein-coupled P2Y receptors that respond to ATP and other nucleotides. Accumulating evidence reveals a prominent role for P2Y receptors in AD pathology, including Aβ production and elimination, neuroinflammation, neuronal function and cerebral blood flow. PMID:25179475

  10. 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%)…

  11. 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…

  12. ARF6-dependent regulation of P2Y receptor traffic and function in human platelets.

    PubMed

    Kanamarlapudi, Venkateswarlu; Owens, Sian E; Saha, Keya; Pope, Robert J; Mundell, Stuart J

    2012-01-01

    Adenosine diphosphate (ADP) is a critical regulator of platelet activation, mediating its actions through two G protein-coupled receptors, the P2Y(1) and P2Y(12) purinoceptors. Recently, we demonstrated that P2Y(1) and P2Y(12) purinoceptor activities are rapidly and reversibly modulated in human platelets, revealing that the underlying mechanism requires receptor internalization and subsequent trafficking as an essential part of this process. In this study we investigated the role of the small GTP-binding protein ADP ribosylation factor 6 (ARF6) in the internalization and function of P2Y(1) and P2Y(12) purinoceptors in human platelets. ARF6 has been implicated in the internalization of a number of GPCRs, although its precise molecular mechanism in this process remains unclear. In this study we show that activation of either P2Y(1) or P2Y(12) purinoceptors can stimulate ARF6 activity. Further blockade of ARF6 function either in cell lines or human platelets blocks P2Y purinoceptor internalization. This blockade of receptor internalization attenuates receptor resensitization. Furthermore, we demonstrate that Nm23-H1, a nucleoside diphosphate (NDP) kinase regulated by ARF6 which facilitates dynamin-dependent fission of coated vesicles during endocytosis, is also required for P2Y purinoceptor internalization. These data describe a novel function of ARF6 in the internalization of P2Y purinoceptors and demonstrate the integral importance of this small GTPase upon platelet ADP receptor function. PMID:22916275

  13. ARF6-Dependent Regulation of P2Y Receptor Traffic and Function in Human Platelets

    PubMed Central

    Kanamarlapudi, Venkateswarlu; Owens, Sian E.; Saha, Keya; Pope, Robert J.; Mundell, Stuart J.

    2012-01-01

    Adenosine diphosphate (ADP) is a critical regulator of platelet activation, mediating its actions through two G protein-coupled receptors, the P2Y1 and P2Y12 purinoceptors. Recently, we demonstrated that P2Y1 and P2Y12 purinoceptor activities are rapidly and reversibly modulated in human platelets, revealing that the underlying mechanism requires receptor internalization and subsequent trafficking as an essential part of this process. In this study we investigated the role of the small GTP-binding protein ADP ribosylation factor 6 (ARF6) in the internalization and function of P2Y1 and P2Y12 purinoceptors in human platelets. ARF6 has been implicated in the internalization of a number of GPCRs, although its precise molecular mechanism in this process remains unclear. In this study we show that activation of either P2Y1 or P2Y12 purinoceptors can stimulate ARF6 activity. Further blockade of ARF6 function either in cell lines or human platelets blocks P2Y purinoceptor internalization. This blockade of receptor internalization attenuates receptor resensitization. Furthermore, we demonstrate that Nm23-H1, a nucleoside diphosphate (NDP) kinase regulated by ARF6 which facilitates dynamin-dependent fission of coated vesicles during endocytosis, is also required for P2Y purinoceptor internalization. These data describe a novel function of ARF6 in the internalization of P2Y purinoceptors and demonstrate the integral importance of this small GTPase upon platelet ADP receptor function. PMID:22916275

  14. Caged Agonist of P2Y1 and P2Y12 Receptors for Light-Directed Facilitation of Platelet Aggregation

    PubMed Central

    Gao, Zhan-Guo; Hechler, Béatrice; Besada, Pedro; Gachet, Christian; Jacobson, Kenneth A.

    2008-01-01

    We have prepared a caged form (MRS2703) of a potent dual agonist of the P2Y1 and P2Y12 nucleotide receptors, 2-MeSADP, by blocking the β-phosphate group with a 1-(3,4-dimethyloxyphenyl)eth-1-yl phosphoester. Although MRS2703 is itself inactive at human P2Y1 and P2Y12 receptors expressed heterologously in 1321N1 astrocytoma cells or in washed human platelets, this derivative readily regenerates the parent agonist upon mild irradiation with long-wave UV light (360 nm). The functional effect of the regenerated agonist was demonstrated by a rise in intracellular calcium mediated by either P2Y1 or P2Y12 receptors in transfected cells. Washed human platelets exposed to a solution of MRS2703 were induced to aggregate upon UV irradiation. At 1.0 μM MRS2703, full aggregation was achieved within one minute of irradiation. Thus, this caged nucleotide promises to be a useful probe for potent P2Y receptor activation with light-directed spatial and temporal control. PMID:18199424

  15. Caged agonist of P2Y1 and P2Y12 receptors for light-directed facilitation of platelet aggregation.

    PubMed

    Gao, Zhan-Guo; Hechler, Béatrice; Besada, Pedro; Gachet, Christian; Jacobson, Kenneth A

    2008-03-15

    We have prepared a caged form (MRS2703) of a potent dual agonist of the P2Y(1) and P2Y(12) nucleotide receptors, 2-MeSADP, by blocking the beta-phosphate group with a 1-(3,4-dimethyloxyphenyl)eth-1-yl phosphoester. Although MRS2703 is itself inactive at human P2Y(1) and P2Y(12) receptors expressed heterologously in 1321N1 astrocytoma cells or in washed human platelets, this derivative readily regenerates the parent agonist upon mild irradiation with long-wave UV light (360 nm). The functional effect of the regenerated agonist was demonstrated by a rise in intracellular calcium mediated by either P2Y(1) or P2Y(12) receptors in transfected cells. Washed human platelets exposed to a solution of MRS2703 were induced to aggregate upon UV irradiation. At 1.0 microM MRS2703, full aggregation was achieved within 1 min of irradiation. Thus, this caged nucleotide promises to be a useful probe for potent P2Y receptor activation with light-directed spatial and temporal control. PMID:18199424

  16. 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.

  17. SD-pair shell model study for {sup 126}Xe and {sup 128}Ba

    SciTech Connect

    Meng Xiangfei; Luo Yanan; Wang, Fu-rong; Pan Feng; Draayer, Jerry P.

    2008-04-15

    The SD-pair shell model is employed to study {sup 126}Xe and {sup 128}Ba. The results show that the spectra and electromagnetic transition strengths can be nicely described in terms of a three-parameter Hamiltonian. In our previous paper, we got a conclusion that the SD-pair approximation improves with the number of SD pairs N. This work shows that this conclusion can be extrapolated to the case with N=5.

  18. 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. PMID:25199943

  19. The Roles of P2Y2 Purinergic Receptors in Osteoblasts and Mechanotransduction

    PubMed Central

    Xing, Yanghui; Gu, Yan; Bresnahan, James J.; Paul, Emmanuel M.; Donahue, Henry J.; You, Jun

    2014-01-01

    We previously demonstrated, using osteoblastic MC3T3-E1 cells, that P2Y2 purinergic receptors are involved in osteoblast mechanotransduction. In this study, our objective was to further investigate, using a knockout mouse model, the roles of P2Y2 receptors in bone mechanobiology. We first examined bone structure with micro-CT and measured bone mechanical properties with three point bending experiments in both wild type mice and P2Y2 knockout mice. We found that bones from P2Y2 knockout mice have significantly decreased bone volume, bone thickness, bone stiffness and bone ultimate breaking force at 17 week old age. In order to elucidate the mechanisms by which P2Y2 receptors contribute to bone biology, we examined differentiation and mineralization of bone marrow cells from wild type and P2Y2 knockout mice. We found that P2Y2 receptor deficiency reduces the differentiation and mineralization of bone marrow cells. Next, we compared the response of primary osteoblasts, from both wild type and P2Y2 knockout mice, to ATP and mechanical stimulation (oscillatory fluid flow), and found that osteoblasts from wild type mice have a stronger response, in terms of ERK1/2 phosphorylation, to both ATP and fluid flow, relative to P2Y2 knockout mice. However, we did not detect any difference in ATP release in response to fluid flow between wild type and P2Y2 knock out osteoblasts. Our findings suggest that P2Y2 receptors play important roles in bone marrow cell differentiation and mineralization as well as in bone cell mechanotransduction, leading to an osteopenic phenotype in P2Y2 knockout mice. PMID:25268784

  20. Identification of a New Morpholine Scaffold as a P2Y12 Receptor Antagonist.

    PubMed

    Ahn, Young Ha; Lee, Joo-Youn; Park, Hee Dong; Kim, Tae Hun; Park, Min Chul; Choi, Gildon; Kim, Sunghoon

    2016-01-01

    The P2Y12 receptor is critical for platelet activation and is an attractive drug target for the prevention of atherothrombotic events. Despite the proven antithrombotic efficacy of P2Y12 inhibitors, these thienopyridine scaffolds are prodrugs that lack important features of the ideal antithrombotic agent. For this reason, ticagrelor-a new chemical class of P2Y12 receptor antagonist-was developed, but it can cause shortness of breath and various types of bleeding. Moreover, ticagrelor is a cytochrome P450 3A4 substrate/inhibitor and, therefore, caution should be exercised when it is used concomitantly with strong CYP3A4 inducers/inhibitors. There is a need for novel P2Y12 receptor antagonist scaffolds that are reversible and have high efficacy without associated side effects. Here, we describe a novel antagonist containing a morpholine moiety that was identified by screening libraries of commercially available compounds. The molecule, Compound E, acted on P2Y12, but not P2Y1 and P2Y13, and exhibited pharmacological characteristics that were distinct from those of ticagrelor, acting instead on P2Y12 via an allosteric mechanism. These results provide a basis for the development/optimization of a new class of P2Y12 antagonists. PMID:27563870

  1. On the Components of Segregation Distortion in DROSOPHILA MELANOGASTER. II. Deletion Mapping and Dosage Analysis of the SD Locus

    PubMed Central

    Brittnacher, John G.; Ganetzky, Barry

    1983-01-01

    Segregation distorter (SD) chromosomes are preferentially transmitted to offspring from heterozygous SD/SD+ males owing to the induced dysfunction of the SD+-bearing sperm. This phenomenon involves at least two major loci: the Sd locus whose presence is necessary for distortion to occur and the Rsp locus which acts as the site of Sd action. Several additional loci on SD chromosomes enhance distortion.—In a previous study deletions were used to map the Sd locus and to determine some of its properties. We have extended this analysis with the isolation and characterization of 14 new deletions in the Sd region. From our results we conclude (1) SD chromosomes contain a single Sd locus located in region 37D2-6 of the salivary gland chromosome map. Deletion of this locus in any of three SD chromosomes now studied results in complete loss of ability to distort a sensitive chromosome; (2) the reduced male fecundity observed in many homozygous SD or SDi/SDj combinations is due at least in part to the action of the Sd locus. The fecundity of these males can be substantially increased by deletion of one Sd locus. Thus, it is the presence of two doses of Sd rather than the absence of Sd+ that produces the lowered male fecundity in SD homozygotes; (3) Sd behaves as a neomorph, whereas Sd+, if it exists at all, is amorphic with respect to segregation distortion; (4) these results support a model in which the Sd product is made in limiting amounts and the interaction of this product with the Rsp locus causes sperm dysfunction. The Sd product appears to act preferentially at Rsps (sensitive-Responder) but may also act at Rspi (insensitive-Responder). PMID:17246120

  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. Quantum phase transitional patterns in the SD-pair shell model

    SciTech Connect

    Luo Yanan; Meng Xiangfei; Zhang Yu; Pan Feng; Draayer, Jerry P.

    2009-07-15

    Patterns of shape-phase transition in the proton-neutron coupled systems are studied within the SD-pair shell model. The results show that some transitional patterns in the SD-pair shell model are similar to the U(5)-SU(3) and U(5)-SO(6) transitions with signatures of the critical point symmetry of the interacting boson model.

  4. 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

  5. Regulation of P2Y1 receptor traffic by sorting Nexin 1 is retromer independent.

    PubMed

    Nisar, Shaista; Kelly, Eamonn; Cullen, Pete J; Mundell, Stuart J

    2010-04-01

    The activity and traffic of G-protein coupled receptors (GPCRs) is tightly controlled. Recent work from our laboratory has shown that P2Y(1) and P2Y(12) responsiveness is rapidly and reversibly modulated in human platelets and that the underlying mechanism requires receptor trafficking as an essential part of this process. However, little is known about the molecular mechanisms underlying P2Y receptor traffic. Sorting nexin 1 (SNX1) has been shown to regulate the endosomal sorting of cell surface receptors either to lysosomes where they are downregulated or back to the cell surface. These functions may in part be due to interactions of SNX1 with the mammalian retromer complex. In this study, we investigated the role of SNX1 in P2Y receptor trafficking. We show that P2Y(1) receptors recycle via a slow recycling pathway that is regulated by SNX1, whereas P2Y(12) receptors return to the cell surface via a rapid route that is SNX1 independent. SNX1 inhibition caused a dramatic increase in the rate of P2Y(1) receptor recycling, whereas inhibition of Vps26 and Vps35 known to be present in retromer had no effect, indicating that SNX1 regulation of P2Y(1) receptor recycling is retromer independent. In addition, inhibition of SNX4, 6 and 17 proteins did not affect P2Y(1) receptor recycling. SNX1 has also been implicated in GPCR degradation; however, we provide evidence that P2Y receptor degradation is SNX1 independent. These data describe a novel function of SNX1 in the regulation of P2Y(1) receptor recycling and suggest that SNX1 plays multiple roles in endocytic trafficking of GPCRs. PMID:20070609

  6. HOW TO MAKE A SINGLETON sdB STAR VIA ACCELERATED STELLAR EVOLUTION

    SciTech Connect

    Clausen, Drew; Wade, Richard A. E-mail: wade@astro.psu.edu

    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.

  7. 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.

  8. Microglial P2Y12 receptors regulate microglial activation and surveillance during neuropathic pain.

    PubMed

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

    2016-07-01

    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 characterised 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 3days post injury in microglial electrophysiology while high resolution two-photon imaging revealed significant changes of both static and dynamic microglial morphological properties by 7days 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

  9. 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

  10. Differential endosomal sorting of a novel P2Y12 purinoreceptor mutant.

    PubMed

    Cunningham, Margaret R; Nisar, Shaista P; Cooke, Alexandra E; Emery, Elizabeth D; Mundell, Stuart J

    2013-05-01

    P2Y12 receptor internalization and recycling play an essential role in ADP-induced platelet activation. Recently, we identified a patient with a mild bleeding disorder carrying a heterozygous mutation of P2Y12 (P341A) whose P2Y12 receptor recycling was significantly compromised. Using human cell line models, we identified key proteins regulating wild-type (WT) P2Y12 recycling and investigated P2Y12 -P341A receptor traffic. Treatment with ADP resulted in delayed Rab5-dependent internalization of P341A when compared with WT P2Y12 . While WT P2Y12 rapidly recycled back to the membrane via Rab4 and Rab11 recycling pathways, limited P341A recycling was observed, which relied upon Rab11 activity. Although minimal receptor degradation was evident, P341A was localized in Rab7-positive endosomes with considerable agonist-dependent accumulation in the trans-Golgi network (TGN). Rab7 activity is known to facilitate recruitment of retromer complex proteins to endosomes to transport cargo to the TGN. Here, we identified that P341A colocalized with Vps26; depletion of which blocked limited recycling and promoted receptor degradation. This study has identified key points of divergence in the endocytic traffic of P341A versus WT-P2Y12 . Given that these pathways are retained in human platelets, this research helps define the molecular mechanisms regulating P2Y12 receptor traffic and explain the compromised receptor function in the platelets of the P2Y12 -P341A-expressing patient. PMID:23387322

  11. New Mechanism for the Enhancement of sd Dominance in Interacting Boson Models

    NASA Astrophysics Data System (ADS)

    Dukelsky, J.; Pittel, S.

    2001-05-01

    We introduce an exactly solvable model for interacting bosons that extend up to high spin and interact through a repulsive pairing force. The model exhibits a phase transition to a state with almost complete sd dominance. The repulsive pairing interaction that underlies the model has a natural microscopic origin in the Pauli exclusion principle between constituent nucleons. As such, repulsive pairing between bosons seems to provide a new mechanism for the enhancement of sd dominance, giving further support for the validity of the sd interacting boson model.

  12. P2Y12 expression and function in alternatively activated human microglia

    PubMed Central

    Ase, Ariel R.; Kinsara, Angham; Rao, Vijayaraghava T.S.; Michell-Robinson, Mackenzie; Leong, Soo Yuen; Butovsky, Oleg; Ludwin, Samuel K.; Séguéla, Philippe; Bar-Or, Amit; Antel, Jack P.

    2015-01-01

    Objective: To investigate and measure the functional significance of altered P2Y12 expression in the context of human microglia activation. Methods: We performed in vitro and in situ experiments to measure how P2Y12 expression can influence disease-relevant functional properties of classically activated (M1) and alternatively activated (M2) human microglia in the inflamed brain. Results: We demonstrated that compared to resting and classically activated (M1) human microglia, P2Y12 expression is increased under alternatively activated (M2) conditions. In response to ADP, the endogenous ligand of P2Y12, M2 microglia have increased ligand-mediated calcium responses, which are blocked by selective P2Y12 antagonism. P2Y12 antagonism was also shown to decrease migratory and inflammatory responses in human microglia upon exposure to nucleotides that are released during CNS injury; no effects were observed in human monocytes or macrophages. In situ experiments confirm that P2Y12 is selectively expressed on human microglia and elevated under neuropathologic conditions that promote Th2 responses, such as parasitic CNS infection. Conclusion: These findings provide insight into the roles of M2 microglia in the context of neuroinflammation and suggest a mechanism to selectively target a functionally unique population of myeloid cells in the CNS. PMID:25821842

  13. Two disparate ligand binding sites in the human P2Y1 receptor

    PubMed Central

    Zhang, Dandan; Gao, Zhan-Guo; Zhang, Kaihua; Kiselev, Evgeny; Crane, Steven; Wang, Jiang; Paoletta, Silvia; Yi, Cuiying; Ma, Limin; Zhang, Wenru; Han, Gye Won; Liu, Hong; Cherezov, Vadim; Katritch, Vsevolod; Jiang, Hualiang; Stevens, Raymond C.; Jacobson, Kenneth A.; Zhao, Qiang; Wu, Beili

    2015-01-01

    In response to adenosine 5′-diphosphate, the P2Y1 receptor (P2Y1R) facilitates platelet aggregation, and thus serves as an important antithrombotic drug target. Here we report the crystal structures of the human P2Y1R in complex with a nucleotide antagonist MRS2500 at 2.7Å resolution, and with a non-nucleotide antagonist BPTU at 2.2Å resolution. The structures reveal two distinct ligand binding sites, providing atomic details of P2Y1R’s unique ligand binding modes. MRS2500 recognizes a binding site within the seven transmembrane bundle of P2Y1R, which, however, is different in shape and location from the nucleotide binding site in previously determined P2Y12R structure. BPTU binds to an allosteric pocket on the external receptor interface with the lipid bilayer, making it the first structurally characterized selective G protein-coupled receptor (GPCR) ligand located entirely outside of the helical bundle. These high-resolution insights into P2Y1R should enable discovery of new orthosteric and allosteric antithrombotic drugs with reduced adverse effects. PMID:25822790

  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. Composition and structure of acid leached LiMn{sub 2-y}Ti{sub y}O{sub 4} (0.2<=y<=1.5) spinels

    SciTech Connect

    Avdeev, Georgi; Amarilla, Jose Manuel; Rojo, Jose Maria; Petrov, Kostadin; Rojas, Rosa Maria

    2009-12-15

    Lithium manganese titanium spinels, LiMn{sub 2-y}Ti{sub y}O{sub 4}, (0.2<=y<=1.5) have been synthesized by solid-state reaction between TiO{sub 2} (anatase), Li{sub 2}CO{sub 3} and MnCO{sub 3}. Li{sup +} was leached from the powdered reaction products by treatment in excess of 0.2 N HCl at 85 deg. C for 6 h, under reflux. The elemental composition of the acidic solution and solid residues of leaching has been determined by complexometric titration, atomic absorption spectroscopy and X-ray fluorescence analysis. Powder X-ray diffraction was used for structural characterization of the crystalline fraction of the solid residues. It has been found that the amount of Li{sup +} leached from LiMn{sub 2-y}Ti{sub y}O{sub 4} decreases monotonically with increasing y in the interval 0.2<=y<=1.0 and abruptly drops to negligibly small values for y>1.0. The content of Mn and Li in the liquid phase and of Mn and Ti in the solid (amorphous plus crystalline) residue, were related to the composition and cation distribution in the pristine compounds. A new formal chemical equation describing the process of leaching and a mechanism of the structural transformation undergone by the initial solids as a result of Li{sup +} removal has been proposed. - Graphical abstract: Schematic representation of the acid leaching of LiMn{sub 2-y}Ti{sub y}O{sub 4} (0.2<=y<=1.0).

  16. 5-OMe-UDP is a potent and selective P2Y(6)-receptor agonist.

    PubMed

    Ginsburg-Shmuel, Tamar; Haas, Michael; Schumann, Marlen; Reiser, Georg; Kalid, Ori; Stern, Noa; Fischer, Bilha

    2010-02-25

    P2Y nucleotide receptors (P2Y-Rs) play important physiological roles. However, most of the P2Y-R subtypes are still lacking potent and selective agonists and antagonists. Based on data mining analysis of binding interactions in 44 protein-uridine nucleos(t)ides complexes, we designed uracil nucleotides, substituted at the C5/C6 position. All C6-substituted derivatives were inactive at the P2Y(2,4,6)-Rs, while out of the C5-substituted analogues, only 5-OMe-UD(T)P showed activity. To rationalize the data, the ionization and conformation of these analogues were evaluated. The pK(a) values of most analogues substituted at the C5/C6 positions were unaltered compared to UTP (pK(a) 9.42), except for 5-F-UTP nucleotide (pK(a) 7.85). C6-substituted analogues adopt the syn or high-syn conformations, which are disfavored by the receptors, while 5-OMe-UD(T)P adopt the favored anti conformation. Furthermore, 5-OMe-UDP adopts the S sugar puckering, which is the conformation preferred by the P2Y(6)-R, but not the P2Y(2)- or P2Y(4)-Rs. 5-OMe-UDP fulfills the conformational and H-bonding requirements of P2Y(6)-R, thus, making a potent P2Y(6)-R agonist (EC(50) 0.08 microM), more than UDP (EC(50) 0.14 microM). PMID:20095577

  17. PTM-SD: a database of structurally resolved and annotated posttranslational modifications in proteins

    PubMed Central

    Craveur, Pierrick; Rebehmed, Joseph; de Brevern, Alexandre G.

    2014-01-01

    Posttranslational modifications (PTMs) define covalent and chemical modifications of protein residues. They play important roles in modulating various biological functions. Current PTM databases contain important sequence annotations but do not provide informative 3D structural resource about these modifications. Posttranslational modification structural database (PTM-SD) provides access to structurally solved modified residues, which are experimentally annotated as PTMs. It combines different PTM information and annotation gathered from other databases, e.g. Protein DataBank for the protein structures and dbPTM and PTMCuration for fine sequence annotation. PTM-SD gives an accurate detection of PTMs in structural data. PTM-SD can be browsed by PDB id, UniProt accession number, organism and classic PTM annotation. Advanced queries can also be performed, i.e. detailed PTM annotations, amino acid type, secondary structure, SCOP class classification, PDB chain length and number of PTMs by chain. Statistics and analyses can be computed on a selected dataset of PTMs. Each PTM entry is detailed in a dedicated page with information on the protein sequence, local conformation with secondary structure and Protein Blocks. PTM-SD gives valuable information on observed PTMs in protein 3D structure, which is of great interest for studying sequence–structure– function relationships at the light of PTMs, and could provide insights for comparative modeling and PTM predictions protocols. Database URL: PTM-SD can be accessed at http://www.dsimb.inserm.fr/dsimb_tools/PTM-SD/. PMID:24857970

  18. SdPI, The First Functionally Characterized Kunitz-Type Trypsin Inhibitor from Scorpion Venom

    PubMed Central

    Li, Tian; He, Yawen; Ma, Yibao; Chen, Zongyun; Wu, Yingliang; Li, Wenxin; Cao, Zhijian

    2011-01-01

    Background Kunitz-type venom peptides have been isolated from a wide variety of venomous animals. They usually have protease inhibitory activity or potassium channel blocking activity, which by virtue of the effects on predator animals are essential for the survival of venomous animals. However, no Kunitz-type peptides from scorpion venom have been functionally characterized. Principal Findings A new Kunitz-type venom peptide gene precursor, SdPI, was cloned and characterized from a venom gland cDNA library of the scorpion Lychas mucronatus. It codes for a signal peptide of 21 residues and a mature peptide of 59 residues. The mature SdPI peptide possesses a unique cysteine framework reticulated by three disulfide bridges, different from all reported Kunitz-type proteins. The recombinant SdPI peptide was functionally expressed. It showed trypsin inhibitory activity with high potency (Ki = 1.6×10−7 M) and thermostability. Conclusions The results illustrated that SdPI is a potent and stable serine protease inhibitor. Further mutagenesis and molecular dynamics simulation revealed that SdPI possesses a serine protease inhibitory active site similar to other Kunitz-type venom peptides. To our knowledge, SdPI is the first functionally characterized Kunitz-type trypsin inhibitor derived from scorpion venom, and it represents a new class of Kunitz-type venom peptides. PMID:22087336

  19. 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.

  20. Clinical effects and outcomes with new P2Y12 inhibitors in ACS.

    PubMed

    Collet, Jean-Philippe; O'Connor, Stephen

    2012-02-01

    Thienopyridines have become the cornerstone of treatment for percutaneous coronary intervention although no survival benefit has ever been shown with clopidogrel despite increasing loading doses. Newly developed P2Y12 inhibitors are more potent, more predictable, and have a faster onset of action than clopidogrel, characteristics that make them particularly attractive for high-risk percutaneous coronary intervention (PCI). Four new P2Y12 inhibitors have been tested each of them having particular individual properties. Prasugrel is an oral pro-drug leading to irreversible blockade of the P2Y12 receptor and is approved worldwide for ACS PCI. Ticagrelor is a direct-acting and reversible inhibitor of the P2Y12 receptor with potentially more pleiotropic effects. Cangrelor is an intravenous direct and reversible inhibitor of the P2Y12 receptor providing the highest level of inhibition, and elinogrel is an intravenous and oral P2Y12 antagonist with a direct and reversible action. Both prasugrel and ticagrelor, opposed to clopidogrel, have shown that stronger P2Y12 inhibition led respectively to significant 19 and 16% relative risk reduction of a similar primary end point combining cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke. Both drugs showed a significant 0.6% absolute excess of TIMI major bleeding not related to CABG surgery. Because in clinical trials, patients perceived to be at higher risk of bleeding usually are excluded, the risk of major and even fatal bleeding might even be higher in a 'real-world' setting, i.e. in the elderly patient with comorbidities. On the other hand, these newly developed P2Y12 inhibitors decrease mortality after PCI compared with clopidogrel. The risk/benefit ratio is particularly favorable in PCI for patients with STEMI. PMID:21895760

  1. Impaired Cognition after Stimulation of P2Y1 Receptors in the Rat Medial Prefrontal Cortex

    PubMed Central

    Koch, Holger; Bespalov, Anton; Drescher, Karla; Franke, Heike; Krügel, Ute

    2015-01-01

    We hypothesize that cortical ATP and ADP accumulating in the extracellular space, eg during prolonged network activity, contribute to a decline in cognitive performance in particular via stimulation of the G protein-coupled P2Y1 receptor (P2Y1R) subtype. Here, we report first evidence on P2Y1R-mediated control of cognitive functioning in rats using bilateral microinfusions of the selective agonist MRS2365 into medial prefrontal cortex (mPFC). MRS2365 attenuated prepulse inhibition of the acoustic startle reflex while having no impact on startle amplitude. Stimulation of P2Y1Rs deteriorated performance accuracy in the delayed non-matching to position task in a delay dependent manner and increased the rate of magazine entries consistent with both working memory disturbances and impaired impulse control. Further, MRS2365 significantly impaired performance in the reversal learning task. These effects might be related to MRS2365-evoked increase of dopamine observed by microdialysis to be short-lasting in mPFC and long-lasting in the nucleus accumbens. P2Y1Rs were identified on pyramidal cells and parvalbumin-positive interneurons, but not on tyrosine hydroxylase-positive fibers, which argues for an indirect activation of dopaminergic afferents in the cortex by MRS2365. Collectively, these results suggest that activation of P2Y1Rs in the mPFC impairs inhibitory control and behavioral flexibility mediated by increased mesocorticolimbic activity and local disinhibition. PMID:25027332

  2. Effects of P2Y12 receptor antagonists beyond platelet inhibition - comparison of ticagrelor with thienopyridines.

    PubMed

    Nylander, Sven; Schulz, Rainer

    2016-04-01

    The effect and clinical benefit of P2Y12 receptor antagonists may not be limited to platelet inhibition and the prevention of arterial thrombus formation. Potential additional effects include reduction of the pro-inflammatory role of activated platelets and effects related to P2Y12 receptor inhibition on other cells apart from platelets. P2Y12 receptor antagonists, thienopyridines and ticagrelor, differ in their mode of action being prodrugs instead of direct acting and irreversibly instead of reversibly binding to P2Y12 . These key differences may provide different potential when it comes to additional effects. In addition to P2Y12 receptor blockade, ticagrelor is unique in having the only well-documented additional target of inhibition, the equilibrative nucleoside transporter 1. The current review will address the effects of P2Y12 receptor antagonists beyond platelets and the protection against arterial thrombosis. The discussion will include the potential for thienopyridines and ticagrelor to mediate anti-inflammatory effects, to conserve vascular function, to affect atherosclerosis, to provide cardioprotection and to induce dyspnea. PMID:26758983

  3. Characterization of MODIS SD screen vignetting function using observations from spacecraft yaw maneuvers

    NASA Astrophysics Data System (ADS)

    Wang, Zhipeng; Xiong, Xiaoxiong

    2009-08-01

    The MODIS reflective solar bands (RSB) include both the low-gain and high-gain spectral bands depending on their specific applications. MODIS RSBs are calibrated on-orbit by an on-board solar diffuser. In order to avoid detector response saturation when calibrating the high-gain bands, an optional attenuation screen, made of a metal plate with pinhole arrays, is placed in front of the SD panel. Since no pre-launch system-level characterization was made for the SD screen (SDS) vignetting function (VF), a series of spacecraft (Terra and Aqua) yaw maneuvers were carried out to perform on-orbit characterization of the VF. Assuming that the low-gain bands and the high-gain bands have the same VF, the current VF was derived from yaw observations using the MODIS low-gain bands through taking the ratio of their SD responses with and without the SDS in place. In this study, we attempt to characterize the SDS VF directly using detector responses of individual high-gain bands with the SDS in place only. The corresponding SD responses without the SDS, not available from measurements due to saturation, are calculated using detector gains, the SD bi-directional reflectance factor (BRF), and the view geometry that matches the yaw observations with the SDS in place. Results and discussions are focused on the band dependent and detector dependent features of the SDS VF, and their potential impact on the RSB calibration.

  4. The qSD12 Locus Controls Offspring Tissue-Imposed Seed Dormancy in Rice

    PubMed Central

    Gu, Xing-You; Turnipseed, E. Brent; Foley, Michael E.

    2008-01-01

    Seed component structures were grouped into maternal and offspring (embryo and endosperm) tissues to characterize a dormancy quantitative trait locus (QTL) for tissue-specific function using a marker-assisted genetic approach. The approach was devised to test if genotypic/allelic frequencies of a marker tightly linked to the QTL deviate from Mendelian expectations in germinated and nongerminated subpopulations derived from a segregation population of partially after-ripened seeds and was applied to the dormancy QTL qSD12 and qSD7-1 in a nearly isogenic background of rice. Experimental results unambiguously demonstrated that qSD12 functions in the offspring tissue(s) and suggested that qSD7-1 may control dormancy through the maternal tissues. These experiments also provide the first solid evidence that an offspring tissue-imposed dormancy gene contributes to the segregation distortion in a mapping population developed from partially after-ripened seeds and, in part, to the germination heterogeneity of seeds from hybrid plants. Offspring and maternal tissue-imposed dormancy genes express in very early and late stages of the life cycle, respectively, and interact to provide the species with complementary adaptation strategies. The qSD12 locus was narrowed to the region of ∼600 kbp on a high-resolution map to facilitate cloning and marker-assisted selection of the major dormancy gene. PMID:18711220

  5. The Mass of the sdB Primary of the Binary HS 2333+3927

    NASA Astrophysics Data System (ADS)

    Heber, U.; Drechsel, H.; Karl, C.; Østensen, R.; Folkes, S.; Napiwotzki, R.; Altmann, M.; Cordes, O.; Solheim, J.-E.; Voss, B.; Koester, D.

    2005-07-01

    Short period sdB binaries with cool companions are crucial to understand pre-CV evolution, because they will evolve into cataclysmic variables, when the sdB will have left the extended horizontal branch. Recently we discovered the sixth such system, HS 2333+3927, consisting of an sdB star and an M dwarf (period: 0.172 d) with a very strong reflection effect, but no eclipses. The reflection is stronger than in any of the other similar systems which renders a quantitative spectral analysis very difficult because the Balmer line profiles may be disturbed by the reflected light. A spectroscopic analysis results in {Teff} = 36 500 K, log{g} = 5.70, and log (nHe/nH) = -2.15. Mass-radius relations were derived from the results of the analysis of light and radial-velocity curves. Comparison with the mass-radius relation derived from the surface gravity of the sdB star favours a rather low mass of 0.38 M⊙ for the primary. The mass of the companion is 0.29 M⊙. HS 2333+3927 is the only known sdB+dM system with a period above the CV period gap.

  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. Agonist-bound structure of the human P2Y12 receptor

    PubMed Central

    Zhang, Jin; Zhang, Kaihua; Gao, Zhan-Guo; Paoletta, Silvia; Zhang, Dandan; Han, Gye Won; Li, Tingting; Ma, Limin; Zhang, Wenru; Müller, Christa E.; Yang, Huaiyu; Jiang, Hualiang; Cherezov, Vadim; Katritch, Vsevolod; Jacobson, Kenneth A.; Stevens, Raymond C.; Wu, Beili; Zhao, Qiang

    2014-01-01

    The P2Y12 receptor (P2Y12R), one of eight members of the P2YR family expressed in humans, has been identified as one of the most prominent clinical drug targets for inhibition of platelet aggregation. Consequently, extensive mutagenesis and modeling studies of the P2Y12R have revealed many aspects of agonist/antagonist binding1-4. However, the details of agonist and antagonist recognition and function at the P2Y12R remain poorly understood at the molecular level. Here, we report the structures of the human P2Y12R in complex with a full agonist 2-methylthio-adenosine-5′-diphosphate (2MeSADP, a close analogue of endogenous agonist ADP) at 2.5 Å resolution, and the corresponding ATP derivative 2-methylthio-adenosine-5′-triphosphate (2MeSATP) at 3.1 Å resolution. Analysis of these structures, together with the structure of the P2Y12R with antagonist ethyl 6-(4-((benzylsulfonyl)carbamoyl)piperidin-1-yl)-5-cyano-2-methylnicotinate (AZD1283)5, reveals dramatic conformational changes between nucleotide and non-nucleotide ligand complexes in the extracellular regions, providing the first insight into a different ligand binding landscape in the δ-group of class A G protein-coupled receptors (GPCRs). Agonist and non-nucleotide antagonist adopt different orientations in the P2Y12R, with only partially overlapped binding pockets. The agonist-bound P2Y12R structure answers long-standing ambiguities surrounding P2Y12R-agonist recognition, and reveals interactions with several residues that had not been reported to be involved in agonist binding. As a first example of a GPCR where agonist access to the binding pocket requires large scale rearrangements in the highly malleable extracellular region, the structural studies therefore will provide invaluable insight into the pharmacology and mechanisms of action of agonists and different classes of antagonists for the P2Y12R and potentially for other closely related P2YRs. PMID:24784220

  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. PMID:25756125

  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. Effect of P2Y12 inhibitors on inflammation and immunity.

    PubMed

    Thomas, Mark R; Storey, Robert F

    2015-08-31

    Platelet P2Y12 inhibitors form a major part of the treatment strategy for patients with acute coronary syndromes (ACS) due to the importance of the platelet P2Y12 receptor in mediating the pathophysiology of arterial thrombosis. It has been increasingly recognised that platelets also have a critical role in inflammation and immune responses. P2Y12 inhibitors reduce platelet release of pro-inflammatory α-granule contents and the formation of pro-inflammatory platelet-leukocyte aggregates. These are important mediators of inflammation in a variety of different contexts. Clinical evidence shows that P2Y12 inhibition by clopidogrel is associated with a reduction in platelet-related mediators of inflammation, such as soluble P-selectin and CD40L, following atherothrombosis. Clopidogrel in addition to aspirin, compared to aspirin alone, also reduces markers of systemic inflammation such as tumour necrosis factor (TNF) α and C-reactive protein (CRP) following ACS. The more potent thienopyridine P2Y12 inhibitor, prasugrel, has been shown to decrease platelet P-selectin expression and platelet-leukocyte aggregate formation compared to clopidogrel. The PLATO study suggested that the novel P2Y12 inhibitor ticagrelor might improve clinical outcomes from pulmonary infections and sepsis compared to clopidogrel in patients with ACS. Ticagrelor is a more potent P2Y12 inhibitor than clopidogrel and also inhibits cellular adenosine uptake via equilibrative nucleoside transporter (ENT) 1, whereas clopidogrel does not. Further examination of the involvement of these mechanisms in inflammation and immunity is therefore warranted. PMID:26156883

  11. The Ratio of ADP- to TRAP-Induced Platelet Aggregation Quantifies P2Y12-Dependent Platelet Inhibition Independently of the Platelet Count

    PubMed Central

    Olivier, Christoph B.; Meyer, Melanie; Bauer, Hans; Schnabel, Katharina; Weik, Patrick; Zhou, Qian; Bode, Christoph; Moser, Martin; Diehl, Philipp

    2016-01-01

    Objective This study aimed to assess the association of clinical factors with P2Y12-dependent platelet inhibition as monitored by the ratio of ADP- to TRAP-induced platelet aggregation and conventional ADP-induced aggregation, respectively. Background Controversial findings to identify and overcome high platelet reactivity (HPR) after coronary stent-implantation and to improve clinical outcome by tailored anti-platelet therapy exist. Monitoring anti-platelet therapy ex vivo underlies several confounding parameters causing that ex vivo platelet aggregation might not reflect in vivo platelet inhibition. Methods In a single centre observational study, multiple electrode aggregometry was performed in whole blood of patients after recent coronary stent-implantation. Relative ADP-induced aggregation (r-ADP-agg) was defined as the ratio of ADP- to TRAP- induced aggregation reflecting the individual degree of P2Y12-mediated platelet reactivity. Results Platelet aggregation was assessed in 359 patients. Means (± SD) of TRAP-, ADP-induced aggregation and r-ADP-agg were 794 ± 239 AU*min, 297 ± 153 AU*min and 37 ± 14%, respectively. While ADP- and TRAP-induced platelet aggregation correlated significantly with platelet count (ADP: r = 0.302; p<0.001; TRAP: r = 0.509 p<0.001), r-ADP-agg values did not (r = -0.003; p = 0.960). These findings were unaltered in multivariate analyses adjusting for a range of factors potentially influencing platelet aggregation. The presence of an acute coronary syndrome and body weight were found to correlate with both ADP-induced platelet aggregation and r-ADP-agg. Conclusion The ratio of ADP- to TRAP-induced platelet aggregation quantifies P2Y12-dependent platelet inhibition independently of the platelet count in contrast to conventional ADP-induced aggregation. Furthermore, r-ADP-agg was associated with the presence of an acute coronary syndrome and body weight as well as ADP-induced aggregation. Thus, the r-ADP-agg is a more valid

  12. Shell-model study for neutron-rich sd-shell nuclei

    SciTech Connect

    Kaneko, Kazunari; Sun Yang; Mizusaki, Takahiro; Hasegawa, Munetake

    2011-01-15

    The microscopic structure of neutron-rich sd-shell nuclei is investigated by using the spherical-shell model in the sd-pf valence space with the extended pairing plus quadrupole-quadrupole forces accompanied by the monopole interaction (EPQQM). The calculation reproduces systematically the known energy levels for even-even and odd-mass nuclei including the recent data for {sup 43}S, {sup 46}S, and {sup 47}Ar. In particular, the erosion of the N=28 shell closure in {sup 42}Si can be explained. Our EPQQM results are compared with other shell-model calculations with the SDPF-NR and SDPF-U effective interactions.

  13. Epoxy encapsulation of the Cernox™ SD thermometer for measuring the temperature of surfaces in liquid helium

    NASA Astrophysics Data System (ADS)

    Dhuley, R. C.; Van Sciver, S. W.

    2016-07-01

    We describe a procedure to pot a Cernox™ thermometer with the SD package in Stycast epoxy. The potting adapts the thermometer for measuring the temperature of a surface immersed in liquid helium (LHe) and other cryogens. The technique thermally insulates the sensor chip from the cryogen while preserving the surface mounting capability of the SD package. The potting introduced <1% shift in the resistance, <0.5% shift in the calibration at 4.2 K and 77 K, and provided repeatable measurements during thermal cycles between room temperature and 4.2 K.

  14. 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.

  15. P2Y6 Receptor Potentiates Pro-Inflammatory Responses in Macrophages and Exhibits Differential Roles in Atherosclerotic Lesion Development

    PubMed Central

    Garcia, Ricardo A.; Yan, Mujing; Search, Debra; Zhang, Rongan; Carson, Nancy L.; Ryan, Carol S.; Smith-Monroy, Constance; Zheng, Joanna; Chen, Jian; Kong, Yan; Tang, Huaping; Hellings, Samuel E.; Wardwell-Swanson, Judith; Dinchuk, Joseph E.; Psaltis, George C.; Gordon, David A.; Glunz, Peter W.; Gargalovic, Peter S.

    2014-01-01

    Background P2Y6, a purinergic receptor for UDP, is enriched in atherosclerotic lesions and is implicated in pro-inflammatory responses of key vascular cell types and macrophages. Evidence for its involvement in atherogenesis, however, has been lacking. Here we use cell-based studies and three murine models of atherogenesis to evaluate the impact of P2Y6 deficiency on atherosclerosis. Methodology/Principal Findings Cell-based studies in 1321N1 astrocytoma cells, which lack functional P2Y6 receptors, showed that exogenous expression of P2Y6 induces a robust, receptor- and agonist-dependent secretion of inflammatory mediators IL-8, IL-6, MCP-1 and GRO1. P2Y6-mediated inflammatory responses were also observed, albeit to a lesser extent, in macrophages endogenously expressing P2Y6 and in acute peritonitis models of inflammation. To evaluate the role of P2Y6 in atherosclerotic lesion development, we used P2Y6-deficient mice in three mouse models of atherosclerosis. A 43% reduction in aortic arch plaque was observed in high fat-fed LDLR knockout mice lacking P2Y6 receptors in bone marrow-derived cells. In contrast, no effect on lesion development was observed in fat-fed whole body P2Y6xLDLR double knockout mice. Interestingly, in a model of enhanced vascular inflammation using angiotensin II, P2Y6 deficiency enhanced formation of aneurysms and exhibited a trend towards increased atherosclerosis in the aorta of LDLR knockout mice. Conclusions P2Y6 receptor augments pro-inflammatory responses in macrophages and exhibits a pro-atherogenic role in hematopoietic cells. However, the overall impact of whole body P2Y6 deficiency on atherosclerosis appears to be modest and could reflect additional roles of P2Y6 in vascular disease pathophysiologies, such as aneurysm formation. PMID:25360548

  16. 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.

  17. 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.

  18. P2Y2 and Gq/G11 control blood pressure by mediating endothelial mechanotransduction

    PubMed Central

    Wang, ShengPeng; Iring, András; Strilic, Boris; Albarrán Juárez, Julián; Kaur, Harmandeep; Troidl, Kerstin; Tonack, Sarah; Burbiel, Joachim C.; Müller, Christa E.; Fleming, Ingrid; Lundberg, Jon O.; Wettschureck, Nina; Offermanns, Stefan

    2015-01-01

    Elevated blood pressure is a key risk factor for developing cardiovascular diseases. Blood pressure is largely determined by vasodilatory mediators, such as nitric oxide (NO), that are released from the endothelium in response to fluid shear stress exerted by the flowing blood. Previous work has identified several mechanotransduction signaling processes that are involved in fluid shear stress–induced endothelial effects, but how fluid shear stress initiates the response is poorly understood. Here, we evaluated human and bovine endothelial cells and found that the purinergic receptor P2Y2 and the G proteins Gq/G11 mediate fluid shear stress–induced endothelial responses, including [Ca2+]i transients, activation of the endothelial NO synthase (eNOS), phosphorylation of PECAM-1 and VEGFR-2, as well as activation of SRC and AKT. In response to fluid shear stress, endothelial cells released ATP, which activates the purinergic P2Y2 receptor. Mice with induced endothelium-specific P2Y2 or Gq/G11 deficiency lacked flow-induced vasodilation and developed hypertension that was accompanied by reduced eNOS activation. Together, our data identify P2Y2 and Gq/G11 as a critical endothelial mechanosignaling pathway that is upstream of previously described mechanotransduction processes and demonstrate that P2Y2 and Gq/G11 are required for basal endothelial NO formation, vascular tone, and blood pressure. PMID:26168216

  19. Arrestin Scaffolds NHERF1 to the P2Y12 Receptor to Regulate Receptor Internalization*

    PubMed Central

    Nisar, Shaista P.; Cunningham, Margaret; Saxena, Kunal; Pope, Robert J.; Kelly, Eamonn; Mundell, Stuart J.

    2012-01-01

    We have recently shown in a patient with mild bleeding that the PDZ-binding motif of the platelet G protein-coupled P2Y12 receptor (P2Y12R) is required for effective receptor traffic in human platelets. In this study we show for the first time that the PDZ motif-binding protein NHERF1 exerts a major role in potentiating G protein-coupled receptor (GPCR) internalization. NHERF1 interacts with the C-tail of the P2Y12R and unlike many other GPCRs, NHERF1 interaction is required for effective P2Y12R internalization. In vitro and prior to agonist stimulation P2Y12R/NHERF1 interaction requires the intact PDZ binding motif of this receptor. Interestingly on receptor stimulation NHERF1 no longer interacts directly with the receptor but instead binds to the receptor via the endocytic scaffolding protein arrestin. These findings suggest a novel model by which arrestin can serve as an adaptor to promote NHERF1 interaction with a GPCR to facilitate effective NHERF1-dependent receptor internalization. PMID:22610101

  20. Arrestin scaffolds NHERF1 to the P2Y12 receptor to regulate receptor internalization.

    PubMed

    Nisar, Shaista P; Cunningham, Margaret; Saxena, Kunal; Pope, Robert J; Kelly, Eamonn; Mundell, Stuart J

    2012-07-13

    We have recently shown in a patient with mild bleeding that the PDZ-binding motif of the platelet G protein-coupled P2Y(12) receptor (P2Y(12)R) is required for effective receptor traffic in human platelets. In this study we show for the first time that the PDZ motif-binding protein NHERF1 exerts a major role in potentiating G protein-coupled receptor (GPCR) internalization. NHERF1 interacts with the C-tail of the P2Y(12)R and unlike many other GPCRs, NHERF1 interaction is required for effective P2Y(12)R internalization. In vitro and prior to agonist stimulation P2Y(12)R/NHERF1 interaction requires the intact PDZ binding motif of this receptor. Interestingly on receptor stimulation NHERF1 no longer interacts directly with the receptor but instead binds to the receptor via the endocytic scaffolding protein arrestin. These findings suggest a novel model by which arrestin can serve as an adaptor to promote NHERF1 interaction with a GPCR to facilitate effective NHERF1-dependent receptor internalization. PMID:22610101

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

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-03

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF JUSTICE Certification of the Attorney General; Shannon County, SD In accordance with Section 8 of the Voting Rights Act, 42 U.S.C. 1973f, I hereby certify that in my judgment the appointment of federal observers is necessary to enforce the guarantees of...

  2. 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.

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

    PubMed Central

    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. PMID:24409376

  4. 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....

  5. Quasicontinuous spectrum of γ rays which feed and depopulate SD in ^194Pb.

    NASA Astrophysics Data System (ADS)

    McNabb, D. P.; Cizewski, J. A.; Ding, K.-Y.; Younes, W.; Khoo, T. L.; Lauritsen, T.; Archer, D. E.; Bauer, R. W.; Becker, J. A.; Bernstein, L. A.; Hauschild, K.; Clark, R. M.; Deleplanque, M. A.; Diamond, R. M.; Fallon, P.; Lee, I. Y.; Macchiavelli, A. O.; Stephens, F. S.; Kelly, W. H.

    1996-10-01

    The mechanism for decay from superdeformed (SD) to ``normal'' (ND) states in ^192Hg results in a large quasicontinuum component which can be fit by a statistical model.(R.G. Henry, et al., Phys. Rev. Lett. 73), 777 (1994). Recent experiments(M.J. Brinkman, et al., Phys. Rev. C53), R1461 (1996); T.L. Khoo, et al., Phys. Rev. Lett. 76, 1583 (1996). have also identified discrete one-step decays from SD to ND states in ^194Pb and ^194Hg which have allowed for the determination of excitation energy and spin of the second wells in these nuclei. We used the ^174Yb(^25Mg,5n) reaction at 130 MeV with a backed target and Gammasphere to study the total spectrum of γ rays in coincidence with the yrast SD band in ^194Pb. The response functions of the detectors were previously determined. The results of the preliminary analysis on the quasicontinuous γ rays which feed and depopulate the yrast SD band will be presented. This work was supported in part by the National Science Foundation and the U.S. Department of Energy.

  6. 78 FR 31430 - Proposed Establishment of Class E Airspace; Wagner, SD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-24

    ...This action proposes to establish Class E airspace at Wagner, SD. Controlled airspace is necessary to accommodate new Standard Instrument Approach Procedures (SIAP) at Wagner Municipal Airport. The FAA is taking this action to enhance the safety and management of Instrument Flight Rules (IFR) operations for SIAPs at the...

  7. 78 FR 25232 - Proposed Establishment of Class E Airspace; Parkston, SD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-30

    ...This action proposes to establish Class E airspace at Parkston, SD. Controlled airspace is necessary to accommodate new Standard Instrument Approach Procedures (SIAP) at Parkston Municipal Airport. The FAA is taking this action to enhance the safety and management of Instrument Flight Rules (IFR) operations for SIAPs at the...

  8. 78 FR 49985 - Proposed Establishment of Class E Airspace; Sisseton, SD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-16

    ...This action proposes to establish Class E airspace at Sisseton, SD. Controlled airspace is necessary to accommodate new Standard Instrument Approach Procedures (SIAP) at Sisseton Municipal Airport. The FAA is taking this action to enhance the safety and management of Instrument Flight Rules (IFR) operations for SIAPs at the...

  9. SD-GIS-based temporal-spatial simulation of water quality in sudden water pollution accidents

    NASA Astrophysics Data System (ADS)

    Zhang, Bo; Qin, Yu; Huang, Mingxiang; Sun, Qiang; Li, Shun; Wang, Liqiang; Yu, Chaohui

    2011-07-01

    System dynamics (SD) is well suited for studying dynamic nonlinear complex systems. In this paper, SD is applied to a rapid-onset water pollution accident using a 1-D water quality model and a conceptual GIS-SD framework is constructed to simulate the temporal-spatial changes of pollutant concentration. Based on the component GIS and the SD model, a prototype system of water quality simulation in water pollution accidents is developed. The data collected on the spot in the Songhua River water pollution accident in November 2005 were used for model parameter calibration and model validation. The results showed that: (1) the constructed model could simulate the changes of nitrobenzene concentration with time in the Songhua River water pollution accident, especially during the peak concentration and at the arrival time of peak concentration, and that the simulated values and the on-the-spot monitored values corresponded with each other well; (2) the scenario simulation could be made by adjusting parameters u (longitudinal current velocity), E (longitudinal diffusion coefficient), and k (decay rate coefficient). Such a model can provide decision makers with quantitative information to optimize related emergency response measures.

  10. High Production of Squalene Using a Newly Isolated Yeast-like Strain Pseudozyma sp. SD301.

    PubMed

    Song, Xiaojin; Wang, Xiaolong; Tan, Yanzhen; Feng, Yingang; Li, Wenli; Cui, Qiu

    2015-09-30

    A yeast-like fungus, termed strain SD301, with the ability to produce a high concentration of squalene, was isolated from Shuidong Bay, China. The nucleotide sequence analysis of the internal transcribed spacer (ITS) region of SD301 indicated the strain belonged to Pseudozyma species. The highest biomass and squalene production of SD301 were obtained when glucose and yeast extracts were used as the carbon and nitrogen sources, respectively, with a C/N ratio of 3. The optimal pH and temperature were 6 and 25 °C, with 15 g L(-1) of supplemented sea salt. The maximum squalene productivity reached 0.039 g L(-1) h(-1) in batch fermentation, while the maximum squalene yield of 2.445 g L(-1) was obtained in fed-batch fermentation. According to our knowledge, this is the highest squalene yield produced thus far using fermentation technology, and the newly isolated strain Pseudozyma sp. SD301 is a promising candidate for commercial squalene production. PMID:26350291

  11. Linear in-wavenumber optical spectrum registration in SD-OCT

    NASA Astrophysics Data System (ADS)

    Gelikonov, Grigory V.; Gelikonov, Valentin M.; Shilyagin, Pavel A.

    2012-01-01

    An efficient technique of linear in-wavenumber optical spectrum registration in SD-OCT is proposed. Methods of partial phase correction of registered optical spectrum for in-wavenumber linearization are described and investigated. The decrease sensitivity decay with depth increasing degeneration is presented. The experimental results for sample media are presented.

  12. 78 FR 24228 - Lake Andes National Wildlife Refuge Complex, Lake Andes, SD; Final Comprehensive Conservation Plan

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-24

    ... review and comment following the announcement in the Federal Register on October 29, 2012 ] (77 FR 65574... Fish and Wildlife Service Lake Andes National Wildlife Refuge Complex, Lake Andes, SD; Final... conservation plan and finding of no significant impact (FONSI) for the Lake Andes National Wildlife...

  13. Exploring Stellar Evolution Models of sdB Stars using MESA

    NASA Astrophysics Data System (ADS)

    Schindler, Jan-Torge; Green, Elizabeth M.; Arnett, W. David

    2015-06-01

    Stellar evolution calculations have had great success reproducing the observed atmospheric properties of different classes of stars. Recent detections of g-mode pulsations in evolved He burning stars allow a rare comparison of their internal structure with stellar models. Asteroseismology of subdwarf B (sdB) stars suggests convective cores of 0.22-0.28 M⊙, ≳45% of the total stellar mass. Previous studies found significantly smaller convective core masses (≲0.19 M⊙) at a comparable evolutionary stage. We evolved stellar models with Modules for Experiments in Stellar Astrophysics (MESA) to explore how well the interior structures inferred from asteroseismology can be reproduced by standard algorithms. Our qualitative evolutionary paths, position in the log g-{{T}eff} diagram, and model timescales are consistent with previous results. The sdB masses from our full evolutionary sequences fall within the range of the empirical sdB mass distribution, but are nearly always lower than the median. Using standard MLT with atomic diffusion we find convective core masses of ˜0.17-0.18 M⊙, averaged over the entire sdB lifetime. We can increase the convective core sizes to be as large as those inferred from asteroseismology, but only for extreme values of the overshoot parameter (overshoot gives numerically unstable and physically unrealistic behavior at the boundary). High resolution three-dimensional simulations of turbulent convection in stars suggest that the Schwarzschild criterion for convective mixing systematically underestimates the actual extent of mixing because a boundary layer forms. Accounting for this would decrease the errors in both sdB total and convective core masses.

  14. 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.

  15. Glycoprotein IIb/IIIa and P2Y12 Induction by Oligochitosan Accelerates Platelet Aggregation

    PubMed Central

    Halim, Ahmad Sukari; Hussein, Abdul Rahim; Ujang, Zanariah

    2014-01-01

    Platelet membrane receptor glycoprotein IIb/IIIa (gpiibiiia) is a receptor detected on platelets. Adenosine diphosphate (ADP) activates gpiibiiia and P2Y12, causing platelet aggregation and thrombus stabilization during blood loss. Chitosan biomaterials were found to promote surface induced hemostasis and were capable of activating blood coagulation cascades by enhancing platelet aggregation. Our current findings show that the activation of the gpiibiiia complex and the major ADP receptor P2Y12 is required for platelet aggregation to reach hemostasis following the adherence of various concentrations of chitosan biomaterials [7% N,O-carboxymethylchitosan (NO-CMC) with 0.45 mL collagen, 8% NO-CMC, oligochitosan (O-C), and oligochitosan 53 (O-C 53)]. We studied gpiibiiia and P2Y12 through flow cytometric analysis and western blotting techniques. The highest expression of gpiibiiia was observed with Lyostypt (74.3 ± 7.82%), followed by O-C (65.5 ± 7.17%). Lyostypt and O-C resulted in gpiibiiia expression increases of 29.2% and 13.9%, respectively, compared with blood alone. Western blot analysis revealed that only O-C 53 upregulated the expression of P2Y12 (1.12 ± 0.03-fold) compared with blood alone. Our findings suggest that the regulation of gpiibiiia and P2Y12 levels could be clinically useful to activate platelets to reach hemostasis. Further, we show that the novel oligochitosan is able to induce the increased expression of gpiibiiia and P2Y12, thus accelerating platelet aggregation in vitro. PMID:25247182

  16. LPS-induced systemic inflammation is more severe in P2Y12 null mice.

    PubMed

    Liverani, Elisabetta; Rico, Mario C; Yaratha, Laxmikausthubha; Tsygankov, Alexander Y; Kilpatrick, Laurie E; Kunapuli, Satya P

    2014-02-01

    Thienopyridines are a class of antiplatelet drugs that are metabolized in the liver to several metabolites, of which only one active metabolite can irreversibly antagonize the platelet P2Y12 receptor. Possible effects of these drugs and the role of activated platelets in inflammatory responses have also been investigated in a variety of animal models, demonstrating that thienopyridines could alter inflammation. However, it is not clear whether it is caused only by the P2Y12 antagonism or whether off-target effects of other metabolites also intervene. To address this question, we investigated P2Y12 KO mice during a LPS-induced model of systemic inflammation, and we treated these KO mice with a thienopyridine drug (clopidogrel). Contrary to the reported effects of clopidogrel, numbers of circulating WBCs and plasma levels of cytokines were increased in LPS-exposed KO mice compared with WT in this inflammation model. Moreover, both spleen and bone marrow show an increase in cell content, suggesting a role for P2Y12 in regulation of bone marrow and spleen cellular composition. Finally, the injury was more severe in the lungs of KO mice compared with WT. Interestingly, clopidogrel treatments also exerted protective effects in KO mice, suggesting off-target effects for this drug. In conclusion, the P2Y12 receptor plays an important role during LPS-induced inflammation, and this signaling pathway may be involved in regulating cell content in spleen and bone marrow during LPS systemic inflammation. Furthermore, clopidogrel may have effects that are independent of P2Y12 receptor blockade. PMID:24142066

  17. Geometric, stable and electronic properties of Aun-2Y2 (n = 3-8) clusters

    NASA Astrophysics Data System (ADS)

    Qi, Kai-Tian; Mao, Hua-Ping; Wang, Hong-Yan; Sheng, Yong

    2010-03-01

    Employing first-principles methods, based on the density function theory, and using the LANL2DZ basis sets, the ground-state geometric, the stable and the electronic properties of Aun-2Y2 clusters are investigated in this paper. Meanwhile, the differences in property among pure gold clusters, pure yttrium clusters, gold clusters doped with one yttrium atom, and gold clusters doped with two yttrium atoms are studied. We find that when gold clusters are doped by two yttrium atoms, the odd-even oscillatory behaviours of Aun-1Y and Aun disappear. The properties of Aun-2Y2 clusters are close to those of pure yttrium clusters.

  18. A hot oxidant, 3-NO2Y122 radical, unmasks conformational gating in ribonucleotide reductase.

    PubMed

    Yokoyama, Kenichi; Uhlin, Ulla; Stubbe, JoAnne

    2010-11-01

    Escherichia coli ribonucleotide reductase is an α2β2 complex that catalyzes the conversion of nucleotides to deoxynucleotides and requires a diferric-tyrosyl radical (Y(•)) cofactor to initiate catalysis. The initiation process requires long-range proton-coupled electron transfer (PCET) over 35 Å between the two subunits by a specific pathway (Y(122)(•)→W(48)→Y(356) within β to Y(731)→Y(730)→C(439) within α). The rate-limiting step in nucleotide reduction is the conformational gating of the PCET process, which masks the chemistry of radical propagation. 3-Nitrotyrosine (NO(2)Y) has recently been incorporated site-specifically in place of Y(122) in β2. The protein as isolated contained a diferric cluster but no nitrotyrosyl radical (NO(2)Y(•)) and was inactive. In the present paper we show that incubation of apo-Y(122)NO(2)Y-β2 with Fe(2+) and O(2) generates a diferric-NO(2)Y(•) that has a half-life of 40 s at 25 °C. Sequential mixing experiments, in which the cofactor is assembled to 1.2 NO(2)Y(•)/β2 and then mixed with α2, CDP, and ATP, have been analyzed by stopped-flow absorption spectroscopy, rapid freeze quench EPR spectroscopy, and rapid chemical quench methods. These studies have, for the first time, unmasked the conformational gating. They reveal that the NO(2)Y(•) is reduced to the nitrotyrosinate with biphasic kinetics (283 and 67 s(-1)), that dCDP is produced at 107 s(-1), and that a new Y(•) is produced at 97 s(-1). Studies with pathway mutants suggest that the new Y(•) is predominantly located at 356 in β2. In consideration of these data and the crystal structure of Y(122)NO(2)Y-β2, a mechanism for PCET uncoupling in NO(2)Y(•)-RNR is proposed. PMID:20929229

  19. New insights on pyrimidine signalling within the arterial vasculature - Different roles for P2Y2 and P2Y6 receptors in large and small coronary arteries of the mouse.

    PubMed

    Haanes, Kristian Agmund; Spray, Stine; Syberg, Susanne; Jørgensen, Niklas Rye; Robaye, Bernard; Boeynaems, Jean-Marie; Edvinsson, Lars

    2016-04-01

    Extracellular pyrimidines activate P2Y receptors on both smooth muscle cells and endothelial cells, leading to vasoconstriction and relaxation respectively. The aim of this study was to utilize P2Y knock-out (KO) mice to determine which P2Y receptor subtype are responsible for the contraction and relaxation in the coronary circulation and to establish whether P2Y receptors have different functions along the mouse coronary vascular tree. We tested stable pyrimidine analogues on isolated coronary arteries from P2Y2 and P2Y6 receptor KO mice in a myograph setup. In larger diameter segments of the left descending coronary artery (LAD) (lumen diameter~150μm) P2Y6 is the predominant contractile receptor for both UTP (uridine triphosphate) and UDP (uridine diphosphate) induced contraction. In contrast, P2Y2 receptors mediate endothelial-dependent relaxation. However, in smaller diameter LAD segments (lumen diameter~50μm), the situation is opposite, with P2Y2 being the contractile receptor and P2Y6 functioning as a relaxant receptor along with P2Y2. Immunohistochemistry was used to confirm smooth muscle and endothelial localization of the receptors. In vivo measurements of blood pressure in WT mice revealed a biphasic response to the stable analogue UDPβS. Based on the changes in P2Y receptor functionality along the mouse coronary arterial vasculature, we propose that UTP can act as a vasodilator downstream of its release, after being degraded to UDP, without affecting the contractile pyrimidine receptors. We also propose a model, showing physiological relevance for the changes in purinergic receptor functionality along the mouse coronary vascular tree. PMID:26827897

  20. Gene deletion of P2Y4 receptor lowers exercise capacity and reduces myocardial hypertrophy with swimming exercise.

    PubMed

    Horckmans, Michael; Léon-Gómez, Elvira; Robaye, Bernard; Balligand, Jean-Luc; Boeynaems, Jean-Marie; Dessy, Chantal; Communi, Didier

    2012-10-01

    Nucleotides released within the heart under pathological conditions can be involved in cardioprotection or cardiac fibrosis through the activation purinergic P2Y(2) and P2Y(6) receptors, respectively. We previously demonstrated that adult P2Y(4)-null mice display a microcardia phenotype related to a cardiac angiogenic defect. To evaluate the functional consequences of this defect, we performed here a combination of cardiac monitoring and exercise tests. We investigated the exercise capacity of P2Y(4) wild-type and P2Y(4)-null mice in forced swimming and running tests. Analysis of their stress, locomotion, and resignation was realized in open field, black and white box, and tail suspension experiments. Exercise-induced cardiac hypertrophy was evaluated after repeated and prolonged exercise in P2Y(4) wild-type and P2Y(4)-null hearts. We showed that P2Y(4)-null mice have a lower exercise capacity in both swimming and treadmill tests. This was not related to decreased motivation or increased stress, since open field, white and black box, and mouse tail suspension tests gave comparable results in P2Y(4) wild-type and P2Y(4)-null mice. Heart rate and blood pressure rose normally in P2Y(4)-null swimming mice equipped with a telemetric implant. On the contrary, we observed a delayed recovery of postexercise blood pressure after exercise in P2Y(4)-null mice. The heart rate increment in response to catecholamines was also similar in P2Y(4) wild-type and P2Y(4)-null implanted mice, which is consistent with a similar level of cardiac β-receptor expression. Interestingly, the heart of P2Y(4)-null mice displayed a reduced sympathetic innervation associated with a decreased norepinephrine level. We also demonstrated that exercise-induced cardiac hypertrophy was lower in P2Y(4)-null mice after repeated and prolonged exercise. This was associated with a lower increase in cardiomyocyte size and microvessel density. In conclusion, besides its role in cardiac development, P2Y(4

  1. Automated Segmentability Index for Layer Segmentation of Macular SD-OCT Images

    PubMed Central

    Lee, Kyungmoo; Buitendijk, Gabriëlle H.S.; Bogunovic, Hrvoje; Springelkamp, Henriët; Hofman, Albert; Wahle, Andreas; Sonka, Milan; Vingerling, Johannes R.; Klaver, Caroline C.W.; Abràmoff, Michael D.

    2016-01-01

    Purpose To automatically identify which spectral-domain optical coherence tomography (SD-OCT) scans will provide reliable automated layer segmentations for more accurate layer thickness analyses in population studies. Methods Six hundred ninety macular SD-OCT image volumes (6.0 × 6.0 × 2.3 mm3) were obtained from one eyes of 690 subjects (74.6 ± 9.7 [mean ± SD] years, 37.8% of males) randomly selected from the population-based Rotterdam Study. The dataset consisted of 420 OCT volumes with successful automated retinal nerve fiber layer (RNFL) segmentations obtained from our previously reported graph-based segmentation method and 270 volumes with failed segmentations. To evaluate the reliability of the layer segmentations, we have developed a new metric, segmentability index SI, which is obtained from a random forest regressor based on 12 features using OCT voxel intensities, edge-based costs, and on-surface costs. The SI was compared with well-known quality indices, quality index (QI), and maximum tissue contrast index (mTCI), using receiver operating characteristic (ROC) analysis. Results The 95% confidence interval (CI) and the area under the curve (AUC) for the QI are 0.621 to 0.805 with AUC 0.713, for the mTCI 0.673 to 0.838 with AUC 0.756, and for the SI 0.784 to 0.920 with AUC 0.852. The SI AUC is significantly larger than either the QI or mTCI AUC (P < 0.01). Conclusions The segmentability index SI is well suited to identify SD-OCT scans for which successful automated intraretinal layer segmentations can be expected. Translational Relevance Interpreting the quantification of SD-OCT images requires the underlying segmentation to be reliable, but standard SD-OCT quality metrics do not predict which segmentations are reliable and which are not. The segmentability index SI presented in this study does allow reliable segmentations to be identified, which is important for more accurate layer thickness analyses in research and population studies. PMID:27066311

  2. KIC 7668647: a 14 day beaming sdB+WD binary with a pulsating subdwarf

    NASA Astrophysics Data System (ADS)

    Telting, J. H.; Baran, A. S.; Nemeth, P.; Østensen, R. H.; Kupfer, T.; Macfarlane, S.; Heber, U.; Aerts, C.; Geier, S.

    2014-10-01

    The recently discovered subdwarf B (sdB) pulsator KIC 7668647 is one of the 18 pulsating sdB stars detected in the Kepler field. It features a rich g-mode frequency spectrum, with a few low-amplitude p-modes at short periods. This makes it a promising target for a seismic study aiming to constrain the internal structure of this star, and of sdB stars in general. We use new ground-based low-resolution spectroscopy, and the near-continuous 2.88 year Kepler light curve, to reveal that KIC 7668647 consists of a subdwarf B star with an unseen white-dwarf companion with an orbital period of 14.2 d. An orbit with a radial-velocity amplitude of 39 km s-1 is consistently determined from the spectra, from the orbital Doppler beaming seen by Kepler at 163 ppm, and from measuring the orbital light-travel delay of 27 s by timing of the many pulsations seen in the Kepler light curve. The white dwarf has a minimum mass of 0.40 M⊙. We use our high signal-to-noise average spectra to study the atmospheric parameters of the sdB star, and find that nitrogen and iron have abundances close to solar values, while helium, carbon, oxygen and silicon are underabundant relative to the solar mixture. We use the full Kepler Q06-Q17 light curve to extract 132 significant pulsation frequencies. Period-spacing relations and multiplet splittings allow us to identify the modal degree ℓ for the majority of the modes. Using theg-mode multiplet splittings we constrain the internal rotation period at the base of the envelope to 46-48 d as a first seismic result for this star. The few p-mode splittings may point at a slightly longer rotation period further out in the envelope of the star. From mode-visibility considerations we derive that the inclination of the rotation axis of the sdB in KIC 7668647 must be around ~60°. Furthermore, we find strong evidence for a few multiplets indicative of degree 3 ≤ ℓ ≤ 8, which is another novelty in sdB-star observations made possible by Kepler. Based on

  3. Test characteristics of two rapid antigen detection tests (SD FK50 and SD FK60) for the diagnosis of malaria in returned travellers

    PubMed Central

    Van der Palen, Mirna; Gillet, Philippe; Bottieau, Emmanuel; Cnops, Lieselotte; Van Esbroeck, Marjan; Jacobs, Jan

    2009-01-01

    Background Two malaria rapid diagnostic tests were evaluated in a travel clinic setting: the SD FK50 Malaria Ag Plasmodium falciparum test (a two-band test) and the SD FK60 Malaria Ag P. falciparum/Pan test (a three-band test). Methods A panel of stored whole blood samples (n = 452 and n = 614 for FK50 and FK60, respectively) from returned travellers was used. The reference method was microscopy with PCR in case of discordant results. Results For both tests, overall sensitivity for the detection of P. falciparum was 93.5%, reaching 97.6% and 100% at parasite densities above 100 and 1,000/μl respectively. Overall sensitivities for Plasmodium vivax, Plasmodium ovale and Plasmodium malariae for the FK60 test were 87.5%, 76.3% and 45.2%, but they reached 92.6% and 90.5% for P. vivax and P. ovale at parasite densities above 500/μl. Specificities were above 95% for all species and both tests when corrected by PCR, with visible histidine-rich protein-2 lines for P. malariae (n = 3) and P. vivax and P. ovale (1 sample each). Line intensities were reproducible and correlated to parasite densities. The FK60 tests provided clues to estimate parasite densities for P. falciparum below or above 1,000/μl. Conclusion Both the FK50 and FK60 performed well for the diagnosis of P. falciparum in the present setting, and the FK60 for the diagnosis of P. vivax and P. ovale at parasite densities > 500/μl. The potential use of the FK60 as a semi-quantitative estimation of parasite density needs to be further explored. PMID:19416497

  4. Activation of Distinct P2Y Receptor Subtypes Stimulates Insulin Secretion in MIN6 Mouse Pancreatic β Cells

    PubMed Central

    Balasubramanian, Ramachandran; de Azua, Inigo Ruiz; Wess, Jürgen; Jacobson, Kenneth A.

    2010-01-01

    Extracellular nucleotides and their receptor antagonists have therapeutic potential in disorders such as inflammation, brain disorders, and cardiovascular diseases. Pancreatic β cells express several purinergic receptors, and reported nucleotide effects on insulin secretion are contradictory. We studied the effect of P2Y receptors on insulin secretion and cell death in MIN6, mouse pancreatic β cells. Expression of P2Y1 and P2Y6 receptors was revealed by total mRNA analysis using RT-PCR. MIN6 cells were stimulated in the presence of 16.7 mM glucose with or without P2Y1 and P2Y6 agonists, 2-MeSADP and Up3U, respectively. Both the agonists increased insulin secretion with EC50 values of 44.6±7.0 nM and 30.7±12.7 nM respectively. The insulin secretion by P2Y1 and P2Y6 agonists was blocked by their selective antagonists MRS2179 and MRS2578, respectively. Binding of the selective P2Y1 receptor antagonist radioligand [125I]MRS2500 in MIN6 cell membranes was saturable (KD 4.74±0.47 nM), and known P2Y1 ligands competed with high affinities. Inflammation and glucose toxicity leads to pancreatic β cell death in diabetes. Flow cytometric analysis revealed that Up3U but not 2-MeSADP protected MIN6 cells against TNF-α induced apoptosis. Overall, the results demonstrate that selective stimulation of P2Y1 and P2Y6 receptors increases insulin secretion that accompanies intracellular calcium release, suggesting potential application of P2Y receptor ligands in the treatment of diabetes. PMID:20067775

  5. Reducing the artifacts in the identification of outer retinal boundary in the SD-OCT image with inherit retinal dystrophies.

    PubMed

    Min Zhang; Sekiguchi, Hiroyuki; Uji, Akihito; Yakami, Masahiro; Togashi, Kaori

    2015-08-01

    This paper presents a new SD-OCT outer retinal boundary identification method based on the improved graph-theoretic approach in SD-OCT retinal image, which is robust to the image quality degradation and the pathological morphology variability. The performance of the proposed method was verified using the SD-OCT image database with inherit retinal dystrophies, which suffer from the artifacts most among different macular degeneration diseases. The experimental results of the subjective evaluation indicated that the identification results using the proposed method was substantially improved compared with the current built-in software in the SD-OCT devices. PMID:26737258

  6. Benzofuran-substituted urea derivatives as novel P2Y(1) receptor antagonists.

    PubMed

    Thalji, Reema K; Aiyar, Nambi; Davenport, Elizabeth A; Erhardt, Joseph A; Kallal, Lorena A; Morrow, Dwight M; Senadhi, Shobha; Burns-Kurtis, Cynthia L; Marino, Joseph P

    2010-07-15

    Benzofuran-substituted urea analogs have been identified as novel P2Y(1) receptor antagonists. Structure-activity relationship studies around the urea and the benzofuran moieties resulted in compounds having improved potency. Several analogs were shown to inhibit ADP-mediated platelet activation. PMID:20542694

  7. P2Y6 Receptor-Mediated Microglial Phagocytosis in Radiation-Induced Brain Injury.

    PubMed

    Xu, Yongteng; Hu, Weihan; Liu, Yimin; Xu, Pengfei; Li, Zichen; Wu, Rong; Shi, Xiaolei; Tang, Yamei

    2016-08-01

    Microglia are the resident immune cells and the professional phagocytic cells of the CNS, showing a multitude of cellular responses after activation. However, how microglial phagocytosis changes and whether it is involved in radiation-induced brain injury remain unknown. In the current study, we found that microglia were activated and microglial phagocytosis was increased by radiation exposure both in cultured microglia in vitro and in mice in vivo. Radiation increased the protein expression of the purinergic receptor P2Y6 receptor (P2Y6R) located on microglia. The selective P2Y6 receptor antagonist MRS2578 suppressed microglial phagocytosis after radiation exposure. Inhibition of microglial phagocytosis increased inhibitory factor Nogo-A and exacerbated radiation-induced neuronal apoptosis and demyelination. We also found that the levels of protein expression for phosphorylated Ras-related C3 botulinum toxin substrate 1 (Rac1) and myosin light chain kinase (MLCK) were elevated, indicating that radiation exposure activated Rac1 and MLCK. The Rac1 inhibitor NSC23766 suppressed expression of MLCK, indicating that the Rac1-MLCK pathway was involved in microglial phagocytosis. Taken together, these findings suggest that the P2Y6 receptor plays a critical role in mediating microglial phagocytosis in radiation-induced brain injury, which might be a potential strategy for therapeutic intervention to alleviate radiation-induced brain injury. PMID:26099306

  8. 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

  9. Adenine Nucleotide Analogues Locked in a Northern Methanocarba Conformation: Enhanced Stability and Potency as P2Y1 Receptor Agonists

    PubMed Central

    Ravi, R. Gnana; Kim, Hak Sung; Servos, Jörg; Zimmermann, Herbert; Lee, Kyeong; Maddileti, Savitri; Boyer, José L.; Harden, T. Kendall; Jacobson, Kenneth A.

    2016-01-01

    Preference for the Northern (N) ring conformation of the ribose moiety of nucleotide 5′-triphosphate agonists at P2Y1, P2Y2, P2Y4, and P2Y11 receptors, but not P2Y6 receptors, was established using a ring-constrained methanocarba (a 3.1.0-bicyclohexane) ring as a ribose substitute (Kim et al. J. Med. Chem. 2002, 45, 208–218.). We have now combined the ring-constrained (N)-methanocarba modification of adenine nucleotides with other functionalities known to enhance potency at P2 receptors. The potency of the newly synthesized analogues was determined in the stimulation of phospholipase C through activation of turkey erythrocyte P2Y1 or human P2Y1 and P2Y2 receptors stably expressed in astrocytoma cells. An (N)-methanocarba-2-methylthio-ADP analogue displayed an EC50 at the hP2Y1 receptor of 0.40 nM and was 55-fold more potent than the corresponding triphosphate and 16-fold more potent than the riboside 5′-diphosphate. 2-Cl–(N)-methanocarba-ATP and its N6-Me analogue were also highly selective, full agonists at P2Y1 receptors. The (N)-methanocarba-2-methylthio and 2-chloromonophosphate analogues were full agonists exhibiting micromolar potency at P2Y1 receptors, while the corresponding ribosides were inactive. Although β,γ-methylene-ATP was inactive at P2Y receptors, β,γ-methylene-(N)-methanocarba-ATP was a potent hP2Y1 receptor agonist with an EC50 of 160 nM and was selective versus hP2Y2 and hP2Y4 receptors. The rates of hydrolysis of Northern (N) and Southern (S) methanocarba analogues of AMP by rat 5′-ectonucleotidase were negligible. The rates of hydrolysis of the corresponding triphosphates by recombinant rat NTPDase1 and 2 were studied. Both isomers were hydrolyzed by NTPDase 1 at about half the rate of ATP hydrolysis. The (N) isomer was hardly hydrolyzed by NTPDase 2, while the (S) isomer was hydrolyzed at one-third of the rate of ATP hydrolysis. This suggests that new, more stable and selective nucleotide agonists may be designed on the basis of

  10. Chiral magnetic effect and SdH oscillations in Dirac and Weyl metals

    NASA Astrophysics Data System (ADS)

    Kharzeev, Dmitri; Monteiro, Gustavo; Abanov, Alexander

    2015-03-01

    In the present work, we consider the interplay of chiral anomaly and Shubnikov-de Haas (SdH) oscillations in recently discovered Dirac metals. The kinetic theory describing the transport in these new materials should account for the chiral anomaly. The unbalanced number of chiral zero-modes in the presence of magnetic field due to the chiral anomaly gives rise to an additional contribution to the electric current - the chiral magnetic effect. The zero-modes are topologically protected from scattering and their contribution to the current leads to a negative magnetoresistance. This effect was recently observed in measurements on the Dirac semimetal Cd3 As2, where the longitudinal (with respect to magnetic field) component of the resistivity tensor shows a negative slope, along with pronounced Shubnikov-de Haas (SdH) oscillations. We develop a combined description of both these phenomena within a chiral kinetic theory.

  11. HS 2333 + 3927: a new sdB binary with a large reflection effect

    NASA Astrophysics Data System (ADS)

    Karl, C. A.; Heber, U.; Drechsel, H.; Napiwotzki, R.; Altmann, M.; Østensen, R.; Folkes, S.; Solheim, J. E.; Cordes, O.; Voss, B.; Koester, D.

    2004-06-01

    We report the discovery of a binary, HS 2233 + 3927, consisting of an sdB star with a faint companion. From its lightcurve the orbital period of 14,844 s, the mass ratio, the inclination, and other system parameters are derived. The companion does not contribute to the optical light of the system except through a strong reflection effect. The semi-amplitude of the radial velocity curve K 1= 89.6 km/s-1 and a mass function of f(m) = 0.013 M ⊙ are determined. A preliminary spectroscopic analysis of the blue spectra using NLTE model atmospheres results in Teff= 36 500 K, log g= 5.70, and log(n He/n H) =-2.15. These parameters are typical for sdB stars, the companion is probably an M dwarf.

  12. Fragmentation-aware service provisioning for advance reservation multicast in SD-EONs.

    PubMed

    Li, Shengru; Lu, Wei; Liu, Xiahe; Zhu, Zuqing

    2015-10-01

    In this paper, we study the service provisioning schemes for dynamic advance reservation (AR) multicast requests in elastic optical networks (EONs). We first propose several algorithms that can handle the service scheduling and routing and spectrum assignment (RSA) of AR multicast requests jointly, including an integrated two-dimensional fragmentation-aware RSA (2D-FMA) that can alleviate the 2D fragmentation caused by light-tree provisioning. Then, we leverage the idea of software-defined EONs (SD-EONs) that utilizes OpenFlow (OF) in the control plane to demonstrate and evaluate the proposed algorithms. Specifically, we build an SD-EON control plane testbed, implement the algorithms in it, and perform control plane experiments on dynamic AR multicast provisioning. The results indicate that 2D-FMA achieves the best blocking performance and provides the shortest average setup delay. PMID:26480094

  13. Correlations of excited states for sd bosons in the presence of random interactions

    SciTech Connect

    Lei, Y.; Zhao, Y. M.; Yoshida, N.; Arima, A.

    2011-04-15

    In this work we study the yrast states of sd-boson systems in the presence of random interactions. It is found that the yrast states with spin-zero ground states among the random ensemble exhibit strong correlations, characterized by anharmonic vibration, s-boson or d-boson condensation, as well as vibrational and rotational motions. We study these correlations explicitly based on their wave functions and the features of two-body interactions in the random ensemble.

  14. 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.

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

    PubMed

    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; Hwang, Dae-Youn

    2014-03-01

    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 (1)H nuclear magnetic resonance ((1)H 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

  16. Symmetry of Isoscalar Matrix Elements and Systematics in the sd and beginning of fp shells

    NASA Astrophysics Data System (ADS)

    Orce, J. N.; Petkov, P.; Velázquez, V.; McKay, C. J.; Lesher, S. R.; Choudry, S.; Mynk, M.; Linnemann, A.; Jolie, J.; von Brentano, P.; Werner, V.; Yates, S. W.; McEllistrem, M. T.

    2006-03-01

    A careful determination of the lifetime and measurement of the branching ratio for decay of the first 2T=1+ state in 42Sc has allowed an accurate experimental test of charge independence in the A = 42 isobaric triplet. A lifetime of 69(17) fs was measured at the University of Kentucky, while relative intensities for the 975 keV and 1586 keV transitions depopulating the first 2T=1+ state have been determined at the University of Cologne as 100(1) and 8(1), respectively. Both measurements give an isoscalar matrix element, M0, of 6.4(9) (W.u.)1/2. This result confirms charge independence for the A=42 isobaric triplet. Shell model calculations have been carried out for understanding the global trend of M0 values for A = 4n + 2 isobaric triplets ranging from A = 18 to A = 42. The 21 (T=1)+ → 01 (T=1)+ transition energies, reduced transition probabilities and M0 values are reproduced to a high degree of accuracy. The trend of M0 strength along the sd shell is interpreted in terms of the shell structure. Certain discrepancies arise at the extremes of the sd shell, for the A = 18 and A = 38 isobaric triplets, which might be explained in terms of the low valence space at the extremes of the sd shell.

  17. 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.

  18. 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

  19. SD-MSAEs: Promoter recognition in human genome based on deep feature extraction.

    PubMed

    Xu, Wenxuan; Zhang, Li; Lu, Yaping

    2016-06-01

    The prediction and recognition of promoter in human genome play an important role in DNA sequence analysis. Entropy, in Shannon sense, of information theory is a multiple utility in bioinformatic details analysis. The relative entropy estimator methods based on statistical divergence (SD) are used to extract meaningful features to distinguish different regions of DNA sequences. In this paper, we choose context feature and use a set of methods of SD to select the most effective n-mers distinguishing promoter regions from other DNA regions in human genome. Extracted from the total possible combinations of n-mers, we can get four sparse distributions based on promoter and non-promoters training samples. The informative n-mers are selected by optimizing the differentiating extents of these distributions. Specially, we combine the advantage of statistical divergence and multiple sparse auto-encoders (MSAEs) in deep learning to extract deep feature for promoter recognition. And then we apply multiple SVMs and a decision model to construct a human promoter recognition method called SD-MSAEs. Framework is flexible that it can integrate new feature extraction or new classification models freely. Experimental results show that our method has high sensitivity and specificity. PMID:27018214

  20. Symmetry of Isoscalar Matrix Elements and Systematics in the sd and beginning of fp shells

    SciTech Connect

    Orce, J. N.; McKay, C. J.; Lesher, S. R.; Choudry, S.; Mynk, M.; McEllistrem, M. T.; Petkov, P.; Velazquez, V.; Linnemann, A.; Jolie, J.; Brentano, P. von; Werner, V.; Yates, S. W.

    2006-03-13

    A careful determination of the lifetime and measurement of the branching ratio for decay of the first 2{sub T=1}{sup +} state in 42Sc has allowed an accurate experimental test of charge independence in the A = 42 isobaric triplet. A lifetime of 69(17) fs was measured at the University of Kentucky, while relative intensities for the 975 keV and 1586 keV transitions depopulating the first 2{sub T=1}{sup +} state have been determined at the University of Cologne as 100(1) and 8(1), respectively. Both measurements give an isoscalar matrix element, M0, of 6.4(9) (W.u.)1/2. This result confirms charge independence for the A=42 isobaric triplet. Shell model calculations have been carried out for understanding the global trend of M0 values for A = 4n + 2 isobaric triplets ranging from A = 18 to A = 42. The 2{sub 1(T=1)}{sup +} {yields} 0{sub 1(T=1)}{sup +} transition energies, reduced transition probabilities and M0 values are reproduced to a high degree of accuracy. The trend of M0 strength along the sd shell is interpreted in terms of the shell structure. Certain discrepancies arise at the extremes of the sd shell, for the A = 18 and A 38 isobaric triplets, which might be explained in terms of the low valence space at the extremes of the sd shell.

  1. 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.

  2. 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).

  3. 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.

  4. Variable Effect of P2Y12 Inhibition on Platelet Thrombus Volume in Flowing Blood

    PubMed Central

    Mendolicchio, G. L.; Zavalloni, D.; Bacci, M.; Corrada, E.; Marconi, M.; Lodigiani, C.; Presbitero, P.; Rota, L.; Ruggeri, Z. M.

    2010-01-01

    Background and objectives Patients treated by percutaneous coronary intervention (PCI) receive aspirin and P2Y12 ADP receptor inhibitors to reduce thrombotic complications. The choice of methodology for monitoring the effects of treatment and assessing its efficacy is still a topic of debate. We evaluated how decreased P2Y12 function influences platelet aggregate (thrombus) size measured ex vivo. Methods and Results We used confocal videomicroscopy to measure in real time the volume of platelet thrombi forming upon blood perfusion over fibrillar collagen type I at the wall shear rate of 1,500 s−1. The average volume was significantly smaller in 31 patients receiving aspirin and clopidogrel (19) or ticlopidine (12) than 21 controls, but individual values were above the lower limit of the normal distribution, albeit mostly within the lower quartile, in 61.3% of cases. Disaggregation of platelet thrombi at later perfusion times occurred frequently in the patients. Vasodilator-stimulated phosphoprotein (VASP) phosphorylation, reflecting P2Y12 inhibition, was also decreased in the patient group and only 22.6% of individual values were above the lower normal limit. We found no correlation between thrombus volume formed onto collagen fibrils and level of P2Y12 inhibition, suggesting that additional and individually variable factors can influence the inhibitory effect of treatment on platelet function. Conclusions Measuring platelet thrombus formation in flowing blood reflects the consequences of anti-platelet therapy in a manner that is not proportional to P2Y12 inhibition. Combining the results of the two assays may improve the assessment of thrombotic risk. PMID:21083646

  5. 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.

  6. Chronic inflammatory pain upregulates expression of P2Y2 receptor in small-diameter sensory neurons.

    PubMed

    Zhu, Huiqin; Yu, Yi; Zheng, Lingyan; Wang, Lu; Li, Chenli; Yu, Jiangyuan; Wei, Jing; Wang, Chuang; Zhang, Junfang; Xu, Shujun; Wei, Xiaofei; Cui, Wei; Wang, Qinwen; Chen, Xiaowei

    2015-12-01

    Roles of ionotropic purinergic (P2X) receptors in chronic pain have been intensively investigated. However, the contribution of metabotropic purinergic (P2Y) receptors to pathological pain is controversial. In the present study, using single cell RT-PCR (reverse transcription-polymerase chain reaction) and single cell nested-PCR techniques, we examined the expression of P2X(2), P2X(3), P2Y(1) and P2Y(2) mRNA transcripts in retrogradely labeled cutaneous sensory neurons from mouse lumber dorsal root ganglia (DRGs) following peripheral inflammation. The percentage of cutaneous sensory neurons expressing P2Y(2) mRNA transcripts increased after complete Freund's adjuvant (CFA) treatment. Particularly, the P2Y(2) mRNA transcripts were more frequently detected in small-diameter cutaneous neurons from CFA-treated mice than those from control mice. Coexpression of P2Y(2) and P2X (P2X(2) or P2X(3)) mRNAs was more frequently observed in cutaneous sensory neurons from CFA-treated mice relative to controls. Pain behavioral tests showed that the blockade of P2Y receptors by suramin attenuated mechanical allodynia evoked either by CFA or uridine triphosphate (UTP), an endogenous P2Y(2) and P2Y(4) agonist. These results suggest that chronic inflammatory pain enhances expression of P2Y(2) receptor in peripheral sensory neurons that innervate the injured tissue and the activation of P2Y receptors contributes to mechanical allodynia following inflammation. PMID:26062804

  7. The influence of P2Y12 receptor deficiency on the platelet inhibitory activities of prasugrel in a mouse model: evidence for specific inhibition of P2Y12 receptors by prasugrel.

    PubMed

    Hashimoto, Masami; Sugidachi, Atsuhiro; Isobe, Takashi; Niitsu, Yoichi; Ogawa, Taketoshi; Jakubowski, Joseph A; Asai, Fumitoshi

    2007-10-01

    Prasugrel is a novel orally active thienopyridine with faster, higher and more reliable inhibition of platelet aggregation than clopidogrel reflecting its metabolism in vivo to an active metabolite with selective P2Y(12) antagonistic activity. Several lines of evidence support the contention that prasugrel provides selective P2Y(12) receptor antagonistic activity. To date, however, direct evidence of P2Y(12) specific action by prasugrel in vivo is limited. In the present study, effects of prasugrel on ex vivo platelet aggregation were examined in wild type (WT) and P2Y(12)(-/-) mice. In WT mice, prasugrel showed platelet inhibition that was 8.2 times more potent than clopidogrel. In P2Y(12)(-/-) mice, ADP induced platelet aggregation was minimal, and its extent was similar to that in prasugrel-treated WT mice. In addition, no further inhibition of platelet aggregation was observed after administration of prasugrel to P2Y(12)(-/-) mice. Furthermore, prasugrel-treated WT mice showed similar aggregation patterns using collagen- and murine PAR-4 agonist peptide to those of P2Y(12)(-/-) mice treated with vehicle or prasugrel. Overall, these results clearly provide additional in vivo evidence that prasugrel has selective P2Y(12) antagonistic activity. PMID:17681285

  8. 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...

  9. Complete Genome Sequence of Geobacter anodireducens SD-1T, a Salt-Tolerant Exoelectrogenic Microbe in Bioelectrochemical Systems.

    PubMed

    Sun, Dan; Cheng, Shaoan; Wang, Aijie; Huang, Fangliang; Liu, Wenzong; Xia, Xue

    2016-01-01

    Strain SD-1 is the type strain of the species Geobacter anodireducens, which was originally isolated from a microbial fuel cell reactor in the United States. The characteristic of this bacterium is its high electrochemical activity. Here, we report the fully assembled genome and plasmid sequence of G. anodireducens SD-1(T). PMID:27257213

  10. Complete Genome Sequence of Geobacter anodireducens SD-1T, a Salt-Tolerant Exoelectrogenic Microbe in Bioelectrochemical Systems

    PubMed Central

    Wang, Aijie; Huang, Fangliang; Liu, Wenzong; Xia, Xue

    2016-01-01

    Strain SD-1 is the type strain of the species Geobacter anodireducens, which was originally isolated from a microbial fuel cell reactor in the United States. The characteristic of this bacterium is its high electrochemical activity. Here, we report the fully assembled genome and plasmid sequence of G. anodireducens SD-1T. PMID:27257213

  11. 40 CFR Table 28 to Subpart G of... - Deck Seam Length Factors a (SD) for Internal Floating Roof Tanks

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 10 2012-07-01 2012-07-01 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...

  12. 40 CFR Table 28 to Subpart G of... - Deck Seam Length Factors a (SD) for Internal Floating Roof Tanks

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 10 2014-07-01 2014-07-01 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...

  13. 40 CFR Table 28 to Subpart G of... - Deck Seam Length Factors a (SD) for Internal Floating Roof Tanks

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 10 2013-07-01 2013-07-01 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...

  14. 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 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...

  15. Activation of P2Y1 and P2Y2 nucleotide receptors by adenosine 5′-triphosphate analogues augmented nerve-mediated relaxation of human corpus cavernosum

    PubMed Central

    Gur, Serap; Hellstrom, Wayne J.G.

    2009-01-01

    Introduction Adenosine 5′-triphosphate (ATP) is a ubiquitous cellular energy source. We evaluated the effect of ATP and its analogues on nonadrenergic and noncholinergic relaxation in precontracted human corpus cavernosal smooth muscle (HCCSM). Methods We obtained specimens of human corpus cavernosum (HCC) from patients undergoing penile prosthesis surgery (patient age 46–70 yr, n = 17) with prior approval from the local institutional review board. Isolated HCC strips were placed in organ baths containing Krebs solution and functional experiments were conducted. Immunohistochemical localization studies were performed to establish the presence of purinergic P2X1, P2Y1 and P2Y2 receptors in HCC. Results The amplitude of relaxation induced by electrical-field stimulation (EFS) on HCC was significantly increased after exposure to ATP (P2X and P2Y agonists), 2-MeSATP (P2Y1 agonist), and uridine 5’ triphosphate (P2Y2 agonist), but not α,β-methylene ATP (P2X1 agonist). The P2X1 antagonist pyridoxal-5’-phosphate-6-azophenyl-2’, 4’-disulfonate, and the nonspecific P2Y antagonist, reactive blue 2, did not inhibit the potentiated response of EFS on HCC. Although immunoreactivity for both P2Y1 and P2Y2 receptors was localized abundantly in HCC, there was only low-level immunostaining for the P2X1 receptor. Conclusion These data demonstrate that nerve-mediated relaxation of HCCSM strips precontracted with phenylephrine in organ bath preparations is amplified by stimulating purinergic P2Y1 and P2Y2 receptors. Although nucleotides are important regulators of HCCSM tone, these observations suggest an independent purinergic relaxing mechanism in the HCC, separate from the better known nitrergic system. PMID:19672446

  16. Thymidine 5'-O-monophosphorothioate induces HeLa cell migration by activation of the P2Y6 receptor.

    PubMed

    Gendaszewska-Darmach, Edyta; Szustak, Marcin

    2016-06-01

    ATP, ADP, UTP, and UDP acting as ligands of specific P2Y receptors activate intracellular signaling cascades to regulate a variety of cellular processes, including proliferation, migration, differentiation, and cell death. Contrary to a widely held opinion, we show here that nucleoside 5'-O-monophosphorothioate analogs, containing a sulfur atom in a place of one nonbridging oxygen atom in a phosphate group, act as ligands for selected P2Y subtypes. We pay particular attention to the unique activity of thymidine 5'-O-monophosphorothioate (TMPS) which acts as a specific partial agonist of the P2Y6 receptor (P2Y6R). We also collected evidence for the involvement of the P2Y6 receptor in human epithelial adenocarcinoma cell line (HeLa) cell migration induced by thymidine 5'-O-monophosphorothioate analog. The stimulatory effect of TMPS was abolished by siRNA-mediated P2Y6 knockdown and diisothiocyanate derivative MRS 2578, a selective antagonist of the P2Y6R. Our results indicate for the first time that increased stability of thymidine 5'-O-monophosphorothioate as well as its affinity toward the P2Y6R may be responsible for some long-term effects mediated by this receptor. PMID:26746211

  17. A novel series of piperazinyl-pyridine ureas as antagonists of the purinergic P2Y12 receptor.

    PubMed

    Bach, Peter; Boström, Jonas; Brickmann, Kay; van Giezen, J J J; Hovland, Ragnar; Petersson, Annika U; Ray, Asim; Zetterberg, Fredrik

    2011-05-15

    A novel series of P2Y(12) antagonists for development of drugs within the antiplatelet area is presented. The synthesis of the piperazinyl-pyridine urea derivatives and their structure-activity relationships (SAR) are described. Several compounds showed P2Y(12) antagonistic activities in the sub-micromolar range. PMID:21507636

  18. Plasmodium falciparum Rosetting Epitopes Converge in the SD3-Loop of PfEMP1-DBL1α

    PubMed Central

    Angeletti, Davide; Albrecht, Letusa; Blomqvist, Karin; Quintana, María del Pilar; Akhter, Tahmina; Bächle, Susanna M.; Sawyer, Alan; Sandalova, Tatyana; Achour, Adnane; Wahlgren, Mats; Moll, Kirsten

    2012-01-01

    The ability of Plasmodium falciparum parasitized RBC (pRBC) to form rosettes with normal RBC is linked to the virulence of the parasite and RBC polymorphisms that weaken rosetting confer protection against severe malaria. The adhesin PfEMP1 mediates the binding and specific antibodies prevent sequestration in the micro-vasculature, as seen in animal models. Here we demonstrate that epitopes targeted by rosette disrupting antibodies converge in the loop of subdomain 3 (SD3) which connects the h6 and h7 α-helices of PfEMP1-DBL1α. Both monoclonal antibodies and polyclonal IgG, that bound to epitopes in the SD3-loop, stained the surface of pRBC, disrupted rosettes and blocked direct binding of recombinant NTS-DBL1α to RBC. Depletion of polyclonal IgG raised to NTS-DBL1α on a SD3 loop-peptide removed the anti-rosetting activity. Immunizations with recombinant subdomain 1 (SD1), subdomain 2 (SD2) or SD3 all generated antibodies reacting with the pRBC-surface but only the sera of animals immunized with SD3 disrupted rosettes. SD3-sequences were found to segregate phylogenetically into two groups (A/B). Group A included rosetting sequences that were associated with two cysteine-residues present in the SD2-domain while group B included those with three or more cysteines. Our results suggest that the SD3 loop of PfEMP1-DBL1α is an important target of anti-rosetting activity, clarifying the molecular basis of the development of variant-specific rosette disrupting antibodies. PMID:23227205

  19. P2Y13 receptors mediate presynaptic inhibition of acetylcholine release induced by adenine nucleotides at the mouse neuromuscular junction.

    PubMed

    Guarracino, Juan F; Cinalli, Alejandro R; Fernández, Verónica; Roquel, Liliana I; Losavio, Adriana S

    2016-06-21

    It is known that adenosine 5'-triphosphate (ATP) is released along with the neurotransmitter acetylcholine (ACh) from motor nerve terminals. At mammalian neuromuscular junctions (NMJs), we have previously demonstrated that ATP is able to decrease ACh secretion by activation of P2Y receptors coupled to pertussis toxin-sensitive Gi/o protein. In this group, the receptor subtypes activated by adenine nucleotides are P2Y12 and P2Y13. Here, we investigated, by means of pharmacological and immunohistochemical assays, the P2Y receptor subtype that mediates the modulation of spontaneous and evoked ACh release in mouse phrenic nerve-diaphragm preparations. First, we confirmed that the preferential agonist for P2Y12-13 receptors, 2-methylthioadenosine 5'-diphosphate trisodium salt hydrate (2-MeSADP), reduced MEPP frequency without affecting MEPP amplitude as well as the amplitude and quantal content of end-plate potentials (EPPs). The effect on spontaneous secretion disappeared after the application of the selective P2Y12-13 antagonists AR-C69931MX or 2-methylthioadenosine 5'-monophosphate triethylammonium salt hydrate (2-MeSAMP). 2-MeSADP was more potent than ADP and ATP in reducing MEPP frequency. Then we demonstrated that the selective P2Y13 antagonist MRS-2211 completely prevented the inhibitory effect of 2-MeSADP on MEPP frequency and EPP amplitude, whereas the P2Y12 antagonist MRS-2395 failed to do this. The preferential agonist for P2Y13 receptors inosine 5'-diphosphate sodium salt (IDP) reduced spontaneous and evoked ACh secretion and MRS-2211 abolished IDP-mediated modulation. Immunohistochemical studies confirmed the presence of P2Y13 but not P2Y12 receptors at the end-plate region. Disappearance of P2Y13 receptors after denervation suggests the presynaptic localization of the receptors. We conclude that, at motor nerve terminals, the Gi/o protein-coupled P2Y receptors implicated in presynaptic inhibition of spontaneous and evoked ACh release are of the subtype P2Y

  20. Expression of the P2Y6 purinergic receptor in human T cells infiltrating inflammatory bowel disease.

    PubMed

    Somers, G R; Hammet, F M; Trute, L; Southey, M C; Venter, D J

    1998-11-01

    The human P2Y6 receptor is a member of the G-protein-coupled P2Y purinergic receptor family that responds to extracellular uridine diphosphate (UDP). In previous work, we cloned the human P2Y6 receptor from an activated T-cell library, and others have shown that it is expressed as a 1.9-kb transcript in several lymphoid tissues. This suggests a role for P2Y6 in T-cell function. However, the precise cellular expression pattern and regulation of P2Y6 in immune cells have not yet been established. In this study, we have examined the expression of P2Y6 in a range of tissues containing leukocytes by a combination of in situ hybridization (ISH), Northern blot analysis, and RT-PCR. Northern hybridization revealed that activated peripheral T cells show increased levels of P2Y6 mRNA. Furthermore, RT-PCR analysis of CD4+ and CD8+ subsets illustrated strong expression in both activated CD4+ and CD8+ T cells. Stimulation of resting and activated T cells with the P2Y6 ligand UDP caused a rise in the intracellular free calcium concentration in only the activated subset, indicating the presence of functional receptor. By ISH, P2Y6 expression was detected in the T cells of the thymic medulla and spleen, whereas no signal was detected in the bone marrow, fetal liver, or lymph nodes. T cells are thought to play an important role in the pathogenesis of inflammatory bowel disease (IBD), and because a recent finding has suggested a role for extracellular nucleotides in mediating colonic epithelial cell damage in IBD, we speculated that the P2Y6 nucleotide receptor may be expressed in the T cells infiltrating IBD. ISH results reveal that P2Y6 is highly expressed in the T cells infiltrating active IBD, whereas P2Y6 expression was absent from the T cells of unaffected bowel. These results demonstrate expression and regulation of P2Y6 expression in T cells, and suggest a role for P2Y6 in the pathogenesis of IBD-mediated intestinal damage. PMID:9840612

  1. 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

  2. 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.

  3. 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.

  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. The orbital periods of three sdB eclipsing binary systems

    NASA Astrophysics Data System (ADS)

    Kilkenny, D.

    2014-12-01

    Recent timings of eclipses made between 2011 and 2014 are presented for three binary systems with hot subdwarf primary stars, AA Dor, NY Vir and EC 10246-2707. In the case of AA Dor, the period remains constant. In NY Vir, a rapidly pulsating sdBVr with a cool companion, the period change now appears more complex than can be described by a simple quadratic. EC 10246-2707, which has previously appeared to have a constant period, now appears to be showing a significant period increase. The effect of gravitational radiation in HW Vir-like systems is briefly discussed.

  6. 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.

  7. Clinical outcomes of a 2-y soy isoflavone supplementation in menopausal women1234

    PubMed Central

    Steinberg, Francene M; Murray, Michael J; Lewis, Richard D; Cramer, Margaret A; Amato, Paula; Young, Ronald L; Barnes, Stephen; Konzelmann, Karen L; Fischer, Joan G; Ellis, Kenneth J; Shypailo, Roman J; Fraley, J Kennard; Smith, E O'Brian; Wong, William W

    2011-01-01

    Background: Soy isoflavones are naturally occurring phytochemicals with weak estrogenic cellular effects. Despite numerous clinical trials of short-term isoflavone supplementation, there is a paucity of data regarding longer-term outcomes and safety. Objective: Our aim was to evaluate the clinical outcomes of soy hypocotyl isoflavone supplementation in healthy menopausal women as a secondary outcome of a trial on bone health. Design: A multicenter, randomized, double-blind, placebo-controlled 24-mo trial was conducted to assess the effects of daily supplementation with 80 or 120 mg aglycone equivalent soy hypocotyl isoflavones plus calcium and vitamin D on the health of 403 postmenopausal women. At baseline and after 1 and 2 y, clinical blood chemistry values were measured and a well-woman examination was conducted, which included a mammogram and a Papanicolaou test. A cohort also underwent transvaginal ultrasound measurements to assess endometrial thickness and fibroids. Results: The baseline characteristics of the groups were similar. After 2 y of daily isoflavone exposure, all clinical chemistry values remained within the normal range. The only variable that changed significantly was blood urea nitrogen, which increased significantly after 2 y (P = 0.048) but not after 1 y (P = 0.343) in the supplementation groups. Isoflavone supplementation did not affect blood lymphocyte or serum free thyroxine concentrations. No significant differences in endometrial thickness or fibroids were observed between the groups. Two serious adverse events were detected (one case of breast cancer and one case of estrogen receptor–negative endometrial cancer), which was less than the expected population rate for these cancers. Conclusion: Daily supplementation for 2 y with 80–120 mg soy hypocotyl isoflavones has minimal risk in healthy menopausal women. This trial was registered at clinicaltrials.gov as NCT00665860 PMID:21177797

  8. Novel consequences of voltage-dependence to G-protein-coupled P2Y1 receptors

    PubMed Central

    Gurung, I S; Martinez-Pinna, J; Mahaut-Smith, M P

    2008-01-01

    Background and purpose: Emerging evidence suggests that activation of G-protein-coupled receptors (GPCRs) can be directly regulated by membrane voltage. However, the physiological and pharmacological relevance of this effect remains unclear. We have further examined this phenomenon for P2Y1 receptors in the non-excitable megakaryocyte using a range of agonists and antagonists. Experimental approach: Simultaneous whole-cell patch clamp and fura-2 fluorescence recordings of rat megakaryocytes, which lack voltage-gated Ca2+ influx, were used to examine the voltage-dependence of P2Y1 receptor-evoked IP3-dependent Ca2+ mobilization. Results: Depolarization transiently and repeatedly enhanced P2Y1 receptor-evoked Ca2+ mobilization across a wide concentration range of both weak, partial and full, potent agonists. Moreover, the amplitude of the depolarization-evoked [Ca2+]i increase displayed an inverse relationship with agonist concentration, such that the greatest potentiating effect of voltage was observed at near-threshold levels of agonist. Unexpectedly, depolarization also stimulated an [Ca2+]i increase in the absence of agonist during exposure to the competitive antagonists A3P5PS and MRS2179, or the allosteric enhancer 2,2′-pyridylisatogen tosylate. A further effect of some antagonists, particularly suramin, was to enhance the depolarization-evoked Ca2+ responses during co-application of an agonist. Of several P2Y1 receptor inhibitors, only SCH202676, which has a proposed allosteric mechanism of action, could block ADP-induced voltage-dependent Ca2+ release. Conclusions and implications: The ability of depolarization to potentiate GPCRs at near-threshold agonist concentrations represents a novel mechanism for coincidence detection. Furthermore, the induction and enhancement of voltage-dependent GPCR responses by antagonists has implications for the design of therapeutic compounds. PMID:18414379

  9. On the Diophantine equation x^2+q^2m=2y^p

    NASA Astrophysics Data System (ADS)

    Tengely, Sz

    In this paper we consider the Diophantine equation $x^2+q^{2m}=2y^p$ where $m,p,q,x,y$ are integer unknowns with $m>0,$ $p$ and $q$ are odd primes and $\\gcd(x,y)=1.$ We prove that there are only finitely many solutions $(m,p,q,x,y)$ for which $y$ is not a sum of two consecutive squares. We also study the above equation with fixed $y$ and with fixed $q.$

  10. 6. Credit WCT. Original 21" x 2Y" color negative is ...

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

    6. Credit WCT. Original 2-1" x 2-Y" color negative is housed in the JPL Photography Laboratory, Pasadena, California. JPL staff members Harold Anderson and John Morrow weigh out small amounts of an undetermined substance according to a solid propellant formula (JPL negative no. JPL-10277AC, 27 January 1989). - Jet Propulsion Laboratory Edwards Facility, Weigh & Control Building, Edwards Air Force Base, Boron, Kern County, CA

  11. Nitric Oxide–mediated Modulation of Synaptic Activity by Astrocytic P2Y Receptors

    PubMed Central

    Mehta, Bhupesh; Begum, Gulnaz; Joshi, Nanda B.; Joshi, Preeti G.

    2008-01-01

    We investigated the mechanism of synaptic suppression by P2Y receptors in mixed hippocampal cultures wherein networked neurons exhibit synchronized Ca2+ oscillations (SCO) due to spontaneous glutamatergic synaptic transmission. Pharmacological studies suggested that SCO suppression was mediated by P2Y2/P2Y4 receptors. Immunostaining studies and characterization of ATP/UTP-stimulated Ca2+ responses in solitary neurons and astrocytes revealed that the SCO attenuation was effectuated by astrocytes. We demonstrate that nitric oxide released from activated astrocytes causes synaptic suppression by inhibiting neurotransmitter release. Physiological concentrations of ATP and UTP evoked NO production in astrocytes. SCO suppression was considerably diminished by removal of extracellular NO by membrane-impermeable scavenger c-PTIO or by pretreatment of cells with nitric oxide synthase inhibitor L-NAME. The nitric oxide donor DETA/NO effectively suppressed the SCO. ATP/UTP inhibited KCl-induced exocytosis at presynaptic terminals in an NO-dependent manner. In the absence of exogenously added ATP/UTP, both the NO scavenger and NOS inhibitor enhanced the frequency of SCO, implying that astrocytes release NO during spontaneous synaptic activity and exert a suppressive effect. We report for the first time that under physiological conditions astrocytes use NO as a messenger molecule to modulate the synaptic strength in the networked neurons. PMID:18725529

  12. The role of P2Y1 receptor signaling in central respiratory control.

    PubMed

    Rajani, V; Zhang, Y; Revill, A L; Funk, G D

    2016-06-01

    The profile of P2 receptor signaling in respiratory control has increased substantially since the first suggestions more than 15 years ago of roles in central chemoreception and modulating inspiratory motor outflow. Part of this reflects the paradigm shift that glia participate in information processing and that ATP is a major gliotransmitter. P2 receptors are a diverse family. Here, we review ATP signaling in respiratory control, highlighting G-protein coupled P2Y1 receptors that have been a focus of recent work. Despite strong evidence of a role for glia and P2 receptor signaling in the central chemosensitivity mediated by the retotrapezoid nucleus, P2Y1 receptors do not appear to be directly involved. Evidence that central P2 receptors and glia contribute to the hypoxic ventilatory response is compelling and P2Y1 receptors are the strongest candidate. However, functional significance in vivo, details of the signaling pathways and involvement of other receptor subtypes remain important questions. PMID:26476057

  13. CysLT1 leukotriene receptor antagonists inhibit the effects of nucleotides acting at P2Y receptors

    PubMed Central

    Mamedova, Liaman; Capra, Valérie; Accomazzo, Maria Rosa; Gao, Zhan-Guo; Ferrario, Silvia; Fumagalli, Marta; Abbracchio, Maria P.; Rovati, G. Enrico; Jacobson, Kenneth A.

    2016-01-01

    Montelukast and pranlukast are orally active leukotriene receptor antagonists selective for the CysLT1 receptor. Conversely, the hP2Y1,2,4,6,11,12,13,14 receptors represent a large family of GPCRs responding to either adenine or uracil nucleotides, or to sugar-nucleotides. Montelukast and pranlukast were found to inhibit nucleotide-induced calcium mobilization in a human monocyte-macrophage like cell line, DMSO-differentiated U937 (dU937). Montelukast and pranlukast inhibited the effects of UTP with IC50 values of 7.7 and 4.3 μM, respectively, and inhibited the effects of UDP with IC50 values of 4.5 and 1.6 μM, respectively, in an insurmountable manner. Furthermore, ligand binding studies using [3H]LTD4 excluded the possibility of orthosteric nucleotide binding to the CysLT1 receptor. dU937 cells were shown to express P2Y2, P2Y4, P2Y6, P2Y11, P2Y13 and P2Y14 receptors. Therefore, these antagonists were studied functionally in a heterologous expression system for the human P2Y receptors. In 1321N1 astrocytoma cells stably expressing human P2Y1,2,4,6 receptors, CysLT1 antagonists inhibited both the P2Y agonist-induced activation of phospholipase C and intracellular Ca2+ mobilization. IC50 values at P2Y1 and P2Y6 receptors were <1 μM. In control astrocytoma cells expressing an endogenous M3 muscarinic receptor, 10 μM montelukast had no effect on the carbachol-induced rise in intracellular Ca2+. These data demonstrated that CysLT1 receptor antagonists interact functionally with signaling pathways of P2Y receptors, and this should foster the study of possible implications for the clinical use of these compounds in asthma or in other inflammatory conditions. PMID:16280122

  14. Involvement of Microglial P2Y12 Signaling in Tongue Cancer Pain.

    PubMed

    Tamagawa, T; Shinoda, M; Honda, K; Furukawa, A; Kaji, K; Nagashima, H; Akasaka, R; Chen, J; Sessle, B J; Yonehara, Y; Iwata, K

    2016-09-01

    To elucidate if microglial P2Y12 receptor (P2Y12R) mechanisms are involved in the trigeminal spinal subnucleus caudalis (Vc; also known as the medullary dorsal horn) in intraoral cancer pain, we developed a rat model of tongue cancer pain. Squamous cell carcinoma (SCC) cells were inoculated into the tongue of rats; sham control rats received the vehicle instead. Nociceptive behavior was measured as the head-withdrawal reflex threshold (HWRT) to mechanical or heat stimulation applied to the tongue under light anesthesia. On day 14 after the SCC inoculation, activated microglia and P2Y12R expression were examined immunohistochemically in the Vc. The HWRT was also studied in SCC-inoculated rats with successive intra-cisterna magna (i.c.m.) administration of specific P2Y12R antagonist (MRS2395) or intraperitoneal administration of minocycline, a microglial activation inhibitor. Tongue cancer was histologically verified in SCC-inoculated rats, within which the HWRT to mechanical stimulation of the tongue was significantly decreased, as compared with that of vehicle-inoculated rats, although the HWRT to heat stimulation was not. Microglia was strongly activated on day 14, and the administration of MRS2395 or minocycline reversed associated nocifensive behavior and microglial activation in SCC-inoculated rats for 14 d. The activity of Vc wide dynamic range nociceptive neurons was also recorded electrophysiologically in SCC-inoculated and sham rats. Background activity and noxious mechanically evoked responses of wide dynamic range neurons were significantly increased in SCC-inoculated rats versus sham rats, and background activity and mechanically evoked responses were significantly suppressed following i.c.m. administration of MRS2395 in SCC-inoculated rats as compared with sham. The present findings suggest that SCC inoculation that produces tongue cancer results in strong activation of microglia via P2Y12 signaling in the Vc, in association with increased excitability

  15. Medicinal chemistry of adenosine, P2Y and P2X receptors.

    PubMed

    Jacobson, Kenneth A; Müller, Christa E

    2016-05-01

    Pharmacological tool compounds are now available to define action at the adenosine (ARs), P2Y and P2X receptors. We present a selection of the most commonly used agents to study purines in the nervous system. Some of these compounds, including A1 and A3 AR agonists, P2Y1R and P2Y12R antagonists, and P2X3, P2X4 and P2X7 antagonists, are potentially of clinical use in treatment of disorders of the nervous system, such as chronic pain, neurodegeneration and brain injury. Agonists of the A2AAR and P2Y2R are already used clinically, P2Y12R antagonists are widely used antithrombotics and an antagonist of the A2AAR is approved in Japan for treating Parkinson's disease. The selectivity defined for some of the previously introduced compounds has been revised with updated pharmacological characterization, for example, various AR agonists and antagonists were deemed A1AR or A3AR selective based on human data, but species differences indicated a reduction in selectivity ratios in other species. Also, many of the P2R ligands still lack bioavailability due to charged groups or hydrolytic (either enzymatic or chemical) instability. X-ray crystallographic structures of AR and P2YRs have shifted the mode of ligand discovery to structure-based approaches rather than previous empirical approaches. The X-ray structures can be utilized either for in silico screening of chemically diverse libraries for the discovery of novel ligands or for enhancement of the properties of known ligands by chemical modification. Although X-ray structures of the zebrafish P2X4R have been reported, there is scant structural information about ligand recognition in these trimeric ion channels. In summary, there are definitive, selective agonists and antagonists for all of the ARs and some of the P2YRs; while the pharmacochemistry of P2XRs is still in nascent stages. The therapeutic potential of selectively modulating these receptors is continuing to gain interest in such fields as cancer, inflammation, pain

  16. 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).

  17. SdH oscillations and pressure effect of the Weyl semimetal NbAs

    NASA Astrophysics Data System (ADS)

    Luo, Yongkang; Ghimire, N. J.; Wartenbe, M.; Choi, Hongchul; Neupane, M.; McDonald, R. D.; Bauer, E. D.; Zhu, Jianxin; Thompson, J. D.; Ronning, F.

    Via angular Shubnikov-de Hass (SdH) quantum oscillations measurements, we determine the Fermi surface topology of NbAs. The SdH oscillations consist of two frequencies, corresponding to two Fermi surface extrema: 20.8 T (α-pocket) and 15.6 T (β-pocket). The analysis shows that the β-pocket has a Berry phase of π and a small effective mass 0.033 m0, indicative of a nontrivial topology; whereas the α-pocket has a trivial Berry phase of 0 and a heavier effective mass 0.066 m0. Subtle changes can be seen in the ρxx(T) profiles with pressure up to 2.31 GPa. The Fermi surfaces undergo an anisotropic evolution under pressure, while the topological features of the two pockets remain unchanged. Specific heat measurements reveal a small Sommerfeld coefficient γ0 = 0.09(1) mJ/(molK2) and a large Debye temperature, ΘD = 450(9) K, confirming a ``hard'' crystalline lattice that is stable under pressure. We also studied the Kadowaki-Woods ratio of this low-carrier-density massless system, RKW = 3.2×104µ Ω cm mol2K2J-2. After accounting for the small carrier density in NbAs, this RKW indicates a suppressed transport scattering rate relative to other metals.

  18. SdH oscillations and pressure effect of the Weyl semimetal NbAs

    NASA Astrophysics Data System (ADS)

    Luo, Yongkang; Ghimire, N. J.; Wartenbe, M.; Choi, Hongchul; Neupane, M.; McDonald, R. D.; Bauer, E. D.; Zhu, Jianxin; Thompson, J. D.; Ronning, F.

    Via angular Shubnikov-de Hass (SdH) quantum oscillations measurements, we determine the Fermi surface topology of NbAs. The SdH oscillations consist of two frequencies: 20.8 T (α-pocket) and 15.6 T (β-pocket). The analysis shows that the β-pocket has a Berry phase of π and a small effective mass 0.033 m0, indicative of a nontrivial topology; whereas the α-pocket has a trivial Berry phase of 0 and a heavier effective mass 0.066 m0. Subtle changes can be seen in the ρxx(T) profiles with pressure up to 2.31 GPa. The Fermi surfaces undergo an anisotropic evolution under pressure, while the topological features of the two pockets remain unchanged. Specific heat measurements reveal a small Sommerfeld coefficient γ0 = 0.09(1) mJ/(molK2) and a large Debye temperature, ΘD = 450(9) K, confirming a ``hard'' crystalline lattice. The Kadowaki-Woods ratio and a suppressed transport scattering rate are also studied.

  19. An automated framework for 3D serous pigment epithelium detachment segmentation in SD-OCT images

    PubMed Central

    Sun, Zhuli; Chen, Haoyu; Shi, Fei; Wang, Lirong; Zhu, Weifang; Xiang, Dehui; Yan, Chenglin; Li, Liang; Chen, Xinjian

    2016-01-01

    Pigment epithelium detachment (PED) is an important clinical manifestation of multiple chorioretinal diseases, which can cause loss of central vision. In this paper, an automated framework is proposed to segment serous PED in SD-OCT images. The proposed framework consists of four main steps: first, a multi-scale graph search method is applied to segment abnormal retinal layers; second, an effective AdaBoost method is applied to refine the initial segmented regions based on 62 extracted features; third, a shape-constrained graph cut method is applied to segment serous PED, in which the foreground and background seeds are obtained automatically; finally, an adaptive structure elements based morphology method is applied to remove false positive segmented regions. The proposed framework was tested on 25 SD-OCT volumes from 25 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 90.08%, 0.22%, 91.20% and 92.62%, respectively. The proposed framework can provide clinicians with accurate quantitative information, including shape, size and position of the PED region, which can assist clinical diagnosis and treatment. PMID:26899236

  20. The role of glutathione detoxification pathway in MCLR-induced hepatotoxicity in SD rats.

    PubMed

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

    2015-12-01

    In the present study, we investigated the role of glutathione (GSH) and its related enzymes in Sprague Dawley (SD) rats subjected to microcystin-leucine-arginine (MCLR)-induced hepatotoxicity. SD rats were intraperitoneally (i.p.) injected with MCLR after pretreating with or without buthionine-(S,R)-sulfoximine (BSO), an inhibitor of GSH synthesis. The depletion of GSH with BSO enhanced MCLR-induced oxidative stress, resulting in more severe liver damage and higher MCLR accumulation. Similarly, the contents of malondialdehyde (MDA), total GSH (T-GSH), oxidized GSH (GSSG) and GSH were significantly enhanced in BSO pretreated rats following MCLR treatment. The study showed that the transcription of GSH-related enzymes such as glutathione-S-transferase (GST), γ-glutamylcysteine synthetase (γ-GCS), glutathione reductase (GR) varied in different ways (expect for glutathione peroxidase (GPx), whose gene expression was induced in all treated groups) with or without BSO pretreatment before MCLR exposure, suggesting an adaptative response of GSH-related enzymes at transcription level to combat enhancement of oxidative stress induced by MCLR when pretreated with BSO. These data suggested the tissues with low GSH concentration are highly vulnerable to MCLR toxicity and GSH was critical for the detoxification in MCLR-induced hepatotoxicity in vivo. PMID:24964298

  1. 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).

  2. 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.

  3. 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.

  4. 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.

  5. Global shear velocity heterogeneities in the D″ layer: Inversion from Sd-SKS differential travel times

    NASA Astrophysics Data System (ADS)

    Kuo, Ban-Yuan; Wu, Kuan-Yi

    1997-06-01

    A global map of shear velocity in the D″ layer results from the inversion of 340 differential travel times of diffracted S(SH) minus SKS(SV) (Sd-SKS), from long-period records of global seismic networks. The two-phase design reduces contamination from upper mantle heterogeneities and errors in location and origin time of the events. Additional corrections are made for (1) azimuthal anisotropy at stations where shear wave splitting parameters are available and for (2) travel time perturbations due to lower mantle asphericity, although both effects are minor compared with the observed residuals with respect to the preliminary reference Earth model (PREM) [Dziewonski and Anderson, 1981]. The corrected residuals, ranging from -16 to 18 s, are attributed to anomalies in D″ sampled by both phases. Taking these residuals as data and assuming a constant, 250-km-thick D″ layer, we invert for a lateral velocity variation model of D″ using spherical harmonics. In parameterizing D″ velocities, a high degree expansion (L=14) avoids aliasing, but only the reliably determined, low degree components (LI

  6. Identification of the orphan GPCR, P2Y(10) receptor as the sphingosine-1-phosphate and lysophosphatidic acid receptor.

    PubMed

    Murakami, Masanori; Shiraishi, Akira; Tabata, Kenichi; Fujita, Norihisa

    2008-07-11

    Phylogenetic analysis of transmembrane regions of GPCRs using PHYLIP indicated that the orphan receptor P2Y(10) receptor was classified into the cluster consisting nucleotide and lipid receptors. Based on the results, we studied the abilities of nucleotides and lipids to activate the P2Y(10) receptors. As a result, sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA) evoked intracellular Ca(2+) increases in the CHO cells stably expressing the P2Y(10) fused with a G(16alpha) protein. These Ca(2+) responses were inhibited by S1P receptor and LPA receptor antagonists. The introduction of siRNA designed for P2Y(10) receptor into the P2Y(10)-CHO cells effectively blocked both S1P- and LPA-induced Ca(2+) increases. RT-PCR analysis showed that the mouse P2Y(10) was expressed in reproductive organs, brain, lung and skeletal muscle, suggesting the receptor plays physiological roles throughout the whole body. In conclusion, the P2Y(10) receptor is the first receptor identified as a dual lysophospholipid receptor. PMID:18466763

  7. LPS potentiates nucleotide-induced inflammatory gene expression in macrophages via the upregulation of P2Y2 receptor.

    PubMed

    Eun, So Young; Seo, Jihye; Park, Sang Won; Lee, Jae Heun; Chang, Ki Churl; Kim, Hye Jung

    2014-02-01

    Sepsis is a severe systemic inflammatory response that is associated with high morbidity and mortality. A previous study using an animal model of sepsis showed that survival was significantly lower in WT mice than in P2Y(2) receptor (P2Y(2)R)-deficient mice, suggesting that P2Y(2)R plays a role in septic death. We therefore investigated the role of P2Y(2)R in the inflammatory responses of RAW264.7 murine macrophages to LPS. LPS time-dependently upregulated P2Y(2)R mRNA levels, with a prominent increase observed at 4 h. In addition, LPS increased ATP release in a time dependent manner (5-120 min post LPS treatment). Accordingly, we pretreated cells with LPS for 4 h to induce P2Y(2)R expression and then stimulated the cells with UTP or ATP for 16 h. Interestingly, ATP- or UTP-dependent P2Y(2)R activation in LPS-pretreated cells resulted in dramatically enhanced HMGB1 secretion, COX-2 and iNOS expression, and furthermore PGE2 and NO production compared to LPS treatment alone (4 h) or ATP or UTP treatment alone (16 h), an effect that was inhibited by P2Y(2)R silencing. In addition, these increases in HMGB1 secretion, COX-2 and iNOS expression and PGE(2) and NO production commonly involved the JNK, PKC and PDK pathways. Taken together, these data demonstrate that LPS-dependent upregulation of P2Y(2)R plays a critical role in facilitating the inflammatory responses induced by LPS. PMID:24316256

  8. 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

  9. Thermodynamic stability of La2Mo2-yWyO9, La2Mo2-yWyO8.96+0.02y and La7Mo7(2-y)/2W7y/2O30 (y = 0, 0.5 and 1.0).

    PubMed

    Vega-Castillo, Jesús E; Ravella, Uday K; Corbel, Gwenaël; Lacorre, Philippe; Caneiro, Alberto

    2014-02-14

    The role of W content on the limit oxygen partial pressure (pO2) for stability of fast oxygen-ion conductors La2Mo2-yWyO9 with y = 0, 0.5 and 1.0 has been studied by means of thermogravimetric analysis (TGA) under controlled atmospheres. At 718 °C, below the pO2 stability limit of La2Mo2-yWyO9, the perovskite related compounds La7Mo7(2-y)/2W7y/2O30 were stabilized even for y = 1.0. At 608 °C, the first stage of reduction of β-La2Mo2-yWyO9 leads to the formation of the crystallized oxygen deficient La2Mo2-yWyO8.6+0.02y phase. X-ray powder diffraction shows that the stabilization of the high temperature β-form through tungsten substitution observed in fully oxidized La2Mo2-yWyO9 samples is preserved upon slight reduction. The n-type conductivity arising from the mixed valence state of molybdenum becomes less and less predominant as the W content increases. Further reduction causes amorphization. At both temperatures, W substitution does not enhance the thermodynamic stability of the La2Mo2-yWyO9 ion conductor under a reducing atmosphere but only slows down the kinetics of reduction. PMID:24336778

  10. V{sub 2}Cu{sub 3}Ga{sub 8}, Mo{sub 2}Cu{sub 3}Ga{sub 8} and W{sub 2}Cu{sub 3}Ga{sub 8}-New compounds with a novel order variant of a bcc packing and motifs of self-similarity

    SciTech Connect

    Kuntze, Verena; Lux, Rainer; Hillebrecht, Harald

    2007-01-15

    Single crystals of the new compounds TM{sub 2}Cu{sub 3}Ga{sub 8} (TM=V, Mo, W) were synthesised from the elements. Structure determinations of the isotypic compounds (cI104, space group I4-bar 3d, Z=8; Mo{sub 2}Cu{sub 3}Ga{sub 8}: a=11.9171(10)A, 613 refl., 23 param., R{sub 1}(F)=0.022, wR{sub 2}(F{sup 2})=0.047; W{sub 2}Cu{sub 3}Ga{sub 8}: 11.9248(8)A, 346 refl., 23 param., R{sub 1}(F)=0.048, wR{sub 2}(F{sup 2})=0.086; V{sub 2}Cu{sub 3}Ga{sub 8}: 11.7861(14)A, 374 refl., 24 param., R{sub 1}(F)=0.033, wR{sub 2}(F{sup 2})=0.081) showed a new cubic structure type which can be classified as an ordered defect variant of a bcc packing with a{sup '}=4a: [(TM){sub 2}(Cu){sub 3}({open_square}){sub 3}][Ga{sub 8}]. The coordination polyhedra of the transition metals consist of Ga{sub 8}-cubes with 3 sides capped by Cu leading to coordination number 11. The arrangement of the TMGa{sub 8}Cu{sub 3}-polyhedra is in a way they form itself a 3-fold capped cube. All compositions were confirmed by EDX measurements.

  11. Important operational parameters of membrane bioreactor-sludge disintegration (MBR-SD) system for zero excess sludge production.

    PubMed

    Yoon, Seong-Hoon

    2003-04-01

    In order to prevent excess sludge production during wastewater treatment, a membrane bioreactor-sludge disintegration (MBR-SD) system has been introduced, where the disintegrated sludge is recycled to the bioreactor as a feed solution. In this study, a mathematical model was developed by incorporating a sludge disintegration term into the conventional activated sludge model and the relationships among the operational parameters were investigated. A new definition of F/M ratio for the MBR-SD system was suggested to evaluate the actual organic loading rate. The actual F/M ratio was expected to be much higher than the apparent F/M ratio in MBR-SD. The kinetic parameters concerning the biodegradability of organics hardly affect the system performance. Instead, sludge solubilization ratio (alpha) in the SD process and particulate hydrolysis rate constant (k(h)) in biological reaction determine the sludge disintegration number (SDN), which is related with the overall economics of the MBR-SD system. Under reasonable alpha and k(h) values, SDN would range between 3 and 5 which means the amount of sludge required to be disintegrated would be 3-5 times higher for preventing a particular amount of sludge production. Finally, normalized sludge disintegration rate (q/V) which is needed to maintain a certain level of MLSS in the MBR-SD system was calculated as a function of F/V ratio. PMID:12697235

  12. Absolute density measurement of SD radicals in a supersonic jet at the quantum-noise-limit.

    PubMed

    Mizouri, Arin; Deng, L Z; Eardley, Jack S; Nahler, N Hendrik; Wrede, Eckart; Carty, David

    2013-12-01

    The absolute density of SD radicals in a supersonic jet has been measured down to (1.1 ± 0.1) × 10(5) cm(-3) in a modestly specified apparatus that uses a cross-correlated combination of cavity ring-down and laser-induced fluorescence detection. Such a density corresponds to 215 ± 21 molecules in the probe volume at any given time. The minimum detectable absorption coefficient was quantum-noise-limited and measured to be (7.9 ± 0.6) × 10(-11) cm(-1), in 200 s of acquisition time, corresponding to a noise-equivalent absorption sensitivity for the apparatus of (1.6 ± 0.1) × 10(-9) cm(-1) Hz(-1/2). PMID:24145480

  13. Microsporum fulvum IBRL SD3: as novel isolate for chicken feathers degradation.

    PubMed

    Darah, I; Nur-Diyana, A; Nurul-Husna, S; Jain, K; Lim, Sheh-Hong

    2013-12-01

    Keratinous wastes have increasingly become a problem and accumulate in the environment mainly in the form of feathers, generated mainly from a large number of poultry industries. As keratins are very difficult to degrade by general proteases, they pose a major environmental problem. Therefore, microorganisms which would effectively degrade keratins are needed for recycling such wastes. A geophilic dermatophyte, Microsporum fulvum IBRL SD3 which was isolated from a soil sample collected from a chicken feather dumping site using a baiting technique, was capable to produce keratinase significantly. The crude keratinase was able to degrade whole chicken feathers effectively. The end product of the degradation was protein that contained essential amino acids and may have potential application in animal feed production. Thus, M. fulvum could be a novel organism to produce keratinase for chicken feathers degradation. PMID:24013862

  14. Secondary metabolites from Penicillium pinophilum SD-272, a marine sediment-derived fungus.

    PubMed

    Wang, Ming-Hui; Li, Xiao-Ming; Li, Chun-Shun; Ji, Nai-Yun; Wang, Bin-Gui

    2013-06-01

    Two new secondary metabolites, namely, pinodiketopiperazine A (1) and 6,7-dihydroxy-3-methoxy-3-methylphthalide (2), along with alternariol 2,4-dimethyl ether (3) and L-5-oxoproline methyl ester (4), which were isolated from a natural source for the first time but have been previously synthesized, were characterized from the marine sediment-derived fungus Penicillium pinophilum SD-272. In addition, six known metabolites (5-10) were also identified. Their structures were elucidated by analysis of the NMR and mass spectroscopic data. The absolute configuration of compound 1 was determined by experimental and calculated ECD spectra. Compound 2 displayed potent brine shrimp (Artemia salina) lethality with LD₅₀ 11.2 μM. PMID:23792827

  15. 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.

  16. Isospin Symmetry Along The N=Z Line In The sd Shell

    SciTech Connect

    Della Vedova, F.; Lenzi, S. M.; Farnea, E.; Nespolo, M.; Bazzacco, D.; Brandolini, F.; Lunardi, S.; Menegazzo, R.; Rossi Alvarez, C.; Ur, C.A.; Ionescu-Bujor, M.; Bucurescu, D.; Iordachescu, A.; Marginean, N.; De Angelis, G.; Axiotis, M.; Napoli, D. R.; Bizzeti-Sona, A.; Bizzeti, P.G.

    2005-04-05

    Excited states have been studied in sd-shell nuclei following the 16O (70 MeV) + 24Mg (400 {mu}g/cm2) fusion-evaporation reaction. The GASP spectrometer in conjunction with the charged-particle detector ISIS and the Neutron ring allowed the detection of the {gamma}-rays in coincidence with evaporated light particles. New data on the mirror pairs A=31 and A=35 have been obtained. In particular, the comparison between the level schemes of 35Ar and 35Cl has confirmed the importance of the electromagnetic spin-orbit term, which explains the large Mirror Energy Difference values. Evidence of isospin mixing can be deduced from the E1 transitions.

  17. Support vector machine based IS/OS disruption detection from SD-OCT images

    NASA Astrophysics Data System (ADS)

    Wang, Liyun; Zhu, Weifang; Liao, Jianping; Xiang, Dehui; Jin, Chao; Chen, Haoyu; Chen, Xinjian

    2014-03-01

    In this paper, we sought to find a method to detect the Inner Segment /Outer Segment (IS/OS)disruption region automatically. A novel support vector machine (SVM) based method was proposed for IS/OS disruption detection. The method includes two parts: training and testing. During the training phase, 7 features from the region around the fovea are calculated. Support vector machine (SVM) is utilized as the classification method. In the testing phase, the training model derived is utilized to classify the disruption and non-disruption region of the IS/OS, and calculate the accuracy separately. The proposed method was tested on 9 patients' SD-OCT images using leave-one-out strategy. The preliminary results demonstrated the feasibility and efficiency of the proposed method.

  18. 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.

  19. Toxicity of Methylcyclohexane and Its Effect on the Reproductive System in SD Rats

    PubMed Central

    Kang, Min-Gu; Kim, Tae-Gyun; Kang, Chung-Won

    2011-01-01

    Objectives There is limited data regarding the toxicity of methylcyclohexane, despite its wide use in rubber adhesives, paint diluents, and cleansing agents. This study aimed to verify the toxicity and influence on the reproductive system of methylcyclohexane after its repeated injection in Sprague Dawley (SD) rats. Methods Methylcyclohexane was injected subcutaneously into male and female SD rats once a day, five times a week, for 13 weeks at different doses (0, 10, 100, and 1,000 mg/kg/day) for each group. The toxicity of testing material was verified by observing the change in body and organ weight, hematological change, pathological findings, and effect on the reproductive system at each different concentration. Results In the 1,000 mg/kg/day group, there were cases of animal deaths. In animals that survived, hematological changes, including a decrease in the red blood cell count, were observed. A considerable weight gain or loss and pathological abnormalities in the liver, kidney, and other organs were found. However, the 10 and 100 mg/kg/day groups did not cause deaths or other specific abnormalities. In terms of reproductive toxicity, there were changes in hormone levels, including a significant decrease in hormones such as estradiol and progesterone (p < 0.001) in male animals. Menstrual cycle change for female animals did not show concentration dependency. Conclusion When injected repeatedly for 13 weeks, methylcyclohexane proved to be toxic for the liver, heart, and kidney at a high dose. The absolute toxic dose was 1,000 mg/kg/day, while the no observed adverse effect level was less than 100 mg/kg/day. The substance exerted little influence on the reproductive system. PMID:22953213

  20. SAMI3/SD-WACCM-X simulations of ionospheric variability during northern winter 2009

    NASA Astrophysics Data System (ADS)

    McDonald, S. E.; Sassi, F.; Mannucci, A. J.

    2015-09-01

    We have performed simulations using the Naval Research Laboratory's physics-based model of the ionosphere, Sami3 is A Model of the Ionosphere (SAMI3), to illustrate how neutral wind dynamics is responsible for day-to-day variability of the ionosphere. We have used neutral winds specified from the extended version of the specified dynamics Whole Atmosphere Community Climate Model (SD-WACCM-X), in which meteorology below 92 km is constrained by atmospheric specifications from an operational weather forecast model and reanalysis. To assess the realism of the simulations against observations, we have carried out a case study during January-February 2009, a dynamically disturbed time characterized by a sudden stratospheric warming (SSW) commencing 24 January 2009. Model results are compared with total electron content (TEC) from Jet Propulsion Laboratory global ionospheric maps. We show that SAMI3/SD-WACCM-X captures longitudinal variability in the equatorial ionization anomaly associated with nonmigrating tides, with strongest contributions coming from the diurnal eastward wave number 2 (DE2) and DE3. Both migrating and nonmigrating tides contribute to significant day-to-day variability, with TEC varying up to 16%. Our simulation during the SSW period reveals that at the Jicamarca longitude (285°E) on 27 January 2009 nonmigrating tides contribute to an enhancement of the electron density in the morning followed by a decrease in the afternoon. An enhancement of the semidiurnal eastward wave number 2 (SE2) and SE3 nonmigrating tides, likely associated with the appearance of the SSW, suggests that these tides increase the longitudinal variability of the SSW impact on the ionosphere. The conclusion is that realistic meteorology propagating upward from the lower atmosphere influences the dynamo region and reproduces aspects of the observed variability in the ionosphere.

  1. The study of the Oxytropis kansuensis-induced apoptotic pathway in the cerebrum of SD rats

    PubMed Central

    2013-01-01

    Background Locoweeds cause significant livestock poisoning and economic loss all over the world. Animals can develop locoism, a chronic neurological disease, after grazing on locoweeds. Oxytropis kansuensis is a variety of locoweed that contains swainsonine as its main toxic ingredient. The purpose of this study was to investigate the apoptotic pathway induced in the cerebrum by swainsonine. Results Twenty-four Sprague-Dawley rats were randomly divided into four groups (experimental groups I, II, III and a control group) and 6 SD rats of each group were feed in 3 cages separately. Rats were penned as groups and fed with feeds containing 15% (SW content 0.03‰), 30% (SW content 0.06‰), or 45% (SW content 0.09‰) O. kansuensis for experimental groups I, II, and III, respectively, or complete feed in the case of the control group. One hundred and nineteen days after poisoning, and all rats showed neurological disorders at different degrees, which were considered to be successful established a chronic poisoning model of O. kansuensis. rats were sacrificed and the expression of Fas, FasL, Bcl-2, Bax as well as cleaved caspase-3, -8 and -9 proteins in brain tissues were detected by Western blot. The results showed that SW treatment up-regulated Fas and Fas ligand (FasL) (P < 0.05), and that there was an increase in Bax and a decrease in Bcl-2 protein (P < 0.01). Moreover, SW treatment significantly increases the activation of caspase-3, 8 and -9, the key effectors in apoptosis pathway (P < 0.01). Conclusion Our data suggest that SW induces apoptosis in cells of the brain through death receptor and mitochondria-mediated, caspase-dependent apoptotic pathways in the brain tissue of SD rats. PMID:24148892

  2. 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. PMID:26270883

  3. 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

  4. 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.

  5. A hot oxidant, 3-NO2Y122 radical, unmasks conformational gating in ribonucleotide reductase

    PubMed Central

    Yokoyama, Kenichi; Uhlin, Ulla; Stubbe, JoAnne

    2010-01-01

    Escherichia coli ribonucleotide reductase is an α2β2 complex that catalyzes the conversion of nucleotides to deoxynucleotides and requires a diferric-tyrosyl radical (Y•) cofactor to initiate catalysis. The initiation process requires long range proton-coupled electron transfer (PCET) over 35 Å between the two subunits by a specific pathway (Y122• → W48 → Y356 within β to Y731 → Y730 → C439 within α). The rate-limiting step in nucleotide reduction is the conformational gating of the PCET process, which masks the chemistry of radical propagation. 3-Nitrotyrosine (NO2Y) has recently been incorporated site-specifically in place of Y122 in β2. The protein as isolated contained a diferric cluster, but no nitrotyrosyl radical (NO2Y•) and was inactive. In the present paper we show that incubation of apo-Y122NO2Y-β2 with Fe2+ and O2 generates a diferric-NO2Y• that has a half-life of 40 s at 25 °C. Sequential mixing experiments, in which the cofactor is assembled to 1.2 NO2Y•/β2 and then mixed with α2, CDP, and ATP, have been analyzed by stopped flow spectroscopy, rapid freeze quench EPR spectroscopy and rapid chemical quench methods. These studies have for the first time unmasked the conformational gating. They reveal that the NO2Y• is reduced to the nitrotyrosinate with biphasic kinetics (283 and 67 s-1), that dCDP is produced at 107 s-1, and that a new Y• is produced at 97 s-1. Studies with pathway mutants suggest that the new Y• is predominantly located at 356 in β2. In conjunction with the crystal structure of Y122NO2Y-β2, a mechanism for PCET uncoupling in NO2Y•-RNR is proposed. PMID:20929229

  6. Giant increase in critical current density of KxFe2-ySe₂ single crystals

    DOE PAGESBeta

    Lei, Hechang; Petrovic, C.

    2011-12-28

    The critical current density Jabc of KxFe2-ySe₂ single crystals can be enhanced by more than one order of magnitude, up to ~2.1×10⁴ A/cm² by the post annealing and quenching technique. A scaling analysis reveals the universal behavior of the normalized pinning force as a function of the reduced field for all temperatures, indicating the presence of a single vortex pinning mechanism. The main pinning sources are three-dimensional (3D) point-like normal cores. The dominant vortex interaction with pinning centers is via spatial variations in critical temperature Tc (“δTc pinning”).

  7. Reviewing the controversy surrounding pre-treatment with P2Y12 inhibitors in acute coronary syndrome patients.

    PubMed

    Capodanno, Davide; Angiolillo, Dominick J

    2016-07-01

    Pretreatment with oral P2Y12 inhibitors occurs each time clopidogrel, prasugrel, ticagrelor are given to patients with suspected coronary artery disease before definition of the coronary anatomy. In acute coronary syndromes, the practice of administering oral P2Y12 inhibitors upstream has been the object of significant controversy in recent years, following the publication of two trials of pretreatment in non-ST-segment elevation acute coronary syndromes and ST-segment elevation myocardial infarction, respectively. The introduction in the market of cangrelor - the first intravenous P2Y12 inhibitor - represents a new opportunity but also a new challenge for clinicians. This article reviews current recommendations and supporting evidence surrounding pretreatment with oral and intravenous P2Y12 inhibitors in patients with acute coronary syndromes. PMID:26953527

  8. P2Y2 receptor up-regulation induced by guanosine or UTP in rat brain cultured astrocytes.

    PubMed

    Ballerini, P; Di Iorio, P; Caciagli, F; Rathbone, M P; Jiang, S; Nargi, E; Buccella, S; Giuliani, P; D'Alimonte, I; Fischione, G; Masciulli, A; Romano, S; Ciccarelli, R

    2006-01-01

    Among P2 metabotropic ATP receptors, P2Y2 subtype seems to be peculiar as its upregulation triggers important biological events in different cells types. In non-stimulated cells including astrocytes, P2Y2 receptors are usually expressed at levels lower than P2Y1 sites, however the promoter region of the P2Y2 receptors has not yet been studied and little is known about the mechanisms underlying the regulation of the expression of this ATP receptor. We showed that not only UTP and ATP are the most potent and naturally occurring agonist for P2Y2 sites, but also guanosine induced an up-regulation of astrocyte P2Y2 receptor mRNA evaluated by Northern blot analysis. We also focused our attention on this nucleoside since in our previous studies it was reported to be released by cultured astrocytes and to exert different neuroprotective effects. UTP and guanosine-evoked P2Y2 receptor up-regulation in rat brain cultured astrocytes was linked to an increased P2Y2-mediated intracellular calcium response, thus suggesting an increased P2Y2 activity. Actinomycin D, a RNA polymerase inhibitor, abrogated both UTP and guanosine-mediated P2Y2 up-regulation, thus indicating that de novo transcription was required. The effect of UTP and guanosine was also evaluated in astrocytes pretreated with different inhibitors of signal transduction pathways including ERK, PKC and PKA reported to be involved in the regulation of other cell surface receptor mRNAs. The results show that ERK1-2/MAPK pathway play a key role in the P2Y2 receptor up-regulation mediated by either UTP or guanosine. Moreover, our data suggest that PKA is also involved in guanosine-induced transcriptional activation of P2Y2 mRNA and that increased intracellular calcium levels and PKC activation may also mediate P2Y2 receptor up-regulation triggered by UTP. The extracellular release of ATP under physiological and pathological conditions has been widely studied. On the contrary, little is known about the release of

  9. Central P2Y12 receptor blockade alleviates inflammatory and neuropathic pain and cytokine production in rodents

    PubMed Central

    Horváth, Gergely; Gölöncsér, Flóra; Csölle, Cecilia; Király, Kornél; Andó, Rómeó D.; Baranyi, Mária; Koványi, Bence; Máté, Zoltán; Hoffmann, Kristina; Algaier, Irina; Baqi, Younis; Müller, Christa E.; Von Kügelgen, Ivar; Sperlágh, Beáta

    2014-01-01

    In this study the role of P2Y12 receptors (P2Y12R) was explored in rodent models of inflammatory and neuropathic pain and in acute thermal nociception. In correlation with their activity to block the recombinant human P2Y12R, the majority of P2Y12R antagonists alleviated mechanical hyperalgesia dose-dependently, following intraplantar CFA injection, and after partial ligation of the sciatic nerve in rats. They also caused an increase in thermal nociceptive threshold in the hot plate test. Among the six P2Y12R antagonists evaluated in the pain studies, the selective P2Y12 receptor antagonist PSB-0739 was most potent upon intrathecal application. P2Y12R mRNA and IL-1β protein were time-dependently overexpressed in the rat hind paw and lumbar spinal cord following intraplantar CFA injection. This was accompanied by the upregulation of TNF-α, IL-6 and IL-10 in the hind paw. PSB-0739 (0.3 mg/kg i.t.) attenuated CFA-induced expression of cytokines in the hind paw and of IL-1β in the spinal cord. Subdiaphragmatic vagotomy and the α7 nicotinic acetylcholine receptor antagonist MLA occluded the effect of PSB-0739 (i.t.) on pain behavior and peripheral cytokine induction. Denervation of sympathetic nerves by 6-OHDA pretreatment did not affect the action of PSB-0739. PSB-0739, in an analgesic dose, did not influence motor coordination and platelet aggregation. Genetic deletion of the P2Y12R in mice reproduced the effect of P2Y12R antagonists on mechanical hyperalgesia in inflammatory and neuropathic pain models, on acute thermal nociception and on the induction of spinal IL-1β. Here we report the robust involvement of the P2Y12R in inflammatory pain. The anti-hyperalgesic effect of P2Y12R antagonism could be mediated by the inhibition of both central and peripheral cytokine production and involves α7-receptor mediated efferent pathways. PMID:24971933

  10. Autocrine Regulation of UVA-Induced IL-6 Production via Release of ATP and Activation of P2Y Receptors

    PubMed Central

    Kawano, Ayumi; Kadomatsu, Remi; Ono, Miyu; Kojima, Shuji; Tsukimoto, Mitsutoshi; Sakamoto, Hikaru

    2015-01-01

    Extracellular nucleotides, such as ATP, are released from cells in response to various stimuli and act as intercellular signaling molecules through activation of P2 receptors. Exposure to the ultraviolet radiation A (UVA) component of sunlight causes molecular and cellular damage, and in this study, we investigated the involvement of extracellular nucleotides and P2 receptors in the UVA-induced cellular response. Human keratinocyte-derived HaCaT cells were irradiated with a single dose of UVA (2.5 J/cm2), and ATP release and interleukin (IL)-6 production were measured. ATP was released from cells in response to UVA irradiation, and the release was blocked by pretreatment with inhibitors of gap junction hemichannels or P2X7 receptor antagonist. IL-6 production was increased after UVA irradiation, and this increase was inhibited by ecto-nucleotidase or by antagonists of P2Y11 or P2Y13 receptor. These results suggest that UVA-induced IL-6 production is mediated by release of ATP through hemichannels and P2X7 receptor, followed by activation of P2Y11 and P2Y13 receptors. Interestingly, P2Y11 and P2Y13 were associated with the same pattern of IL-6 production, though they trigger different intracellular signaling cascades: Ca2+-dependent and PI3K-dependent, respectively. Thus, IL-6 production in response to UVA-induced ATP release involves at least two distinct pathways, mediated by activation of P2Y11 and P2Y13 receptors. PMID:26030257

  11. 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. PMID:26520845

  12. 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

  13. An intact PDZ motif is essential for correct P2Y12 purinoceptor traffic in human platelets

    PubMed Central

    Nisar, Shaista; Daly, Martina E.; Federici, Augusto B.; Artoni, Andrea; Mumford, Andrew D.; Watson, Stephen P.

    2011-01-01

    The platelet P2Y12 purinoceptor (P2Y12R), which plays a crucial role in hemostasis, undergoes internalization and subsequent recycling to maintain receptor responsiveness, processes that are essential for normal platelet function. Here, we observe that P2Y12R function is compromised after deletion or mutation of the 4 amino acids at the extreme C-terminus of this receptor (ETPM), a putative postsynaptic density 95/disc large/zonula occludens-1 (PDZ)–binding motif. In cell line models, removal of this sequence or mutation of one of its core residues (P341A), attenuates receptor internalization and receptor recycling back to the membrane, thereby blocking receptor resensitization. The physiologic significance of these findings in the regulation of platelet function is shown by identification of a patient with a heterozygous mutation in the PDZ binding sequence of their P2Y12R (P341A) that is associated with reduced expression of the P2Y12R on the cell surface. Importantly, platelets from this subject showed significantly compromised P2Y12R recycling, emphasizing the importance of the extreme C-terminus of this receptor to ensure correct receptor traffic. PMID:21937696

  14. An intact PDZ motif is essential for correct P2Y12 purinoceptor traffic in human platelets.

    PubMed

    Nisar, Shaista; Daly, Martina E; Federici, Augusto B; Artoni, Andrea; Mumford, Andrew D; Watson, Stephen P; Mundell, Stuart J

    2011-11-17

    The platelet P2Y(12) purinoceptor (P2Y(12)R), which plays a crucial role in hemostasis, undergoes internalization and subsequent recycling to maintain receptor responsiveness, processes that are essential for normal platelet function. Here, we observe that P2Y(12)R function is compromised after deletion or mutation of the 4 amino acids at the extreme C-terminus of this receptor (ETPM), a putative postsynaptic density 95/disc large/zonula occludens-1 (PDZ)-binding motif. In cell line models, removal of this sequence or mutation of one of its core residues (P341A), attenuates receptor internalization and receptor recycling back to the membrane, thereby blocking receptor resensitization. The physiologic significance of these findings in the regulation of platelet function is shown by identification of a patient with a heterozygous mutation in the PDZ binding sequence of their P2Y(12)R (P341A) that is associated with reduced expression of the P2Y(12)R on the cell surface. Importantly, platelets from this subject showed significantly compromised P2Y(12)R recycling, emphasizing the importance of the extreme C-terminus of this receptor to ensure correct receptor traffic. PMID:21937696

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

    PubMed

    Laine, Marc; Paganelli, Franck; Bonello, Laurent

    2016-05-26

    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

  16. 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).

  17. Effect of thermal cycling on ZrO2-Y2O3 thermal barrier coatings

    NASA Technical Reports Server (NTRS)

    Mcdonald, G.; Hendricks, R. C.

    1980-01-01

    The paper studies the comparative life of plasma-sprayed ZrO2-Y2O3 thermal barrier coatings on NiCrAlY bond coats on Rene 41 in short (4 min) and long (57 min) thermal cycles at 1040 C in a 0.3-Mach flame. Attention is given to determining the effect of short- and long-duration cycles on ZrO2-Y2O3 coatings, the cause of any cycle frequency effects, and methods to improve tolerance to thermal stress. Short cycles greatly reduced the life of the ceramic coating in terms of time at temperatures as compared to longer cycles, the failed coating indicating compressive failure. The experiments and stress calculations show that repeatedly subjecting a ceramic coating to high rates of initial heating has a more destructive influence on the coating than sustained operation at temperature. The effect of such thermal compressive stresses might be minimized through coating deposition and thickness control and by turbine cycle measurement to keep starting heating rates below critical values.

  18. 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

  19. 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.

  20. P2Y12 Receptor Antagonists and Morphine: A Dangerous Liaison?

    PubMed

    Giannopoulos, Georgios; Deftereos, Spyridon; Kolokathis, Fotios; Xanthopoulou, Ioanna; Lekakis, John; Alexopoulos, Dimitrios

    2016-09-01

    P2Y12 receptor antagonists, concurrently administered with aspirin in what has come to be commonly called dual antiplatelet therapy, are a mainstay of treatment for patients with acute coronary syndromes. Morphine, on the contrary, is a commonly used drug in the acute phase of acute coronary syndromes to relieve pain-with the added potential benefit of attenuating acutely raised sympathetic tone. In current guidelines, though, morphine is recommended with decreasing strength of recommendation. One reason is that it raises concern regarding the potentially significant interaction with antiplatelet agents, leading to impaired inhibition of platelet activation. In any case, it is still considered a mandatory part of the inventory of available medications in prehospital acute myocardial infarction management. The goal of the present review is to present published evidence on morphine and its potential interactions with P2Y12 receptor antagonists, as well as on the central issue of whether such interactions may underlie clinically significant effects on patient outcomes. PMID:27586412

  1. Dynamin reduces Pyk2 Y402 phosphorylation and SRC binding in osteoclasts.

    PubMed

    Bruzzaniti, Angela; Neff, Lynn; Sandoval, Amanda; Du, Liping; Horne, William C; Baron, Roland

    2009-07-01

    Signaling via the Pyk2-Src-Cbl complex downstream of integrins contributes to the assembly, organization, and dynamics of podosomes, which are the transient adhesion complexes of highly motile cells such as osteoclasts and dendritic cells. We previously demonstrated that the GTPase dynamin is associated with podosomes, regulates actin flux in podosomes, and promotes bone resorption by osteoclasts. We report here that dynamin associates with Pyk2, independent of dynamin's GTPase activity, and reduces Pyk2 Y402 phosphorylation in a GTPase-dependent manner, leading to decreased Src binding to Pyk2. Overexpressing dynamin decreased the macrophage colony-stimulating factor- and adhesion-induced phosphorylation of Pyk2 in osteoclastlike cells, suggesting that dynamin is likely to regulate Src-Pyk2 binding downstream of integrins and growth factor receptors with important cellular consequences. Furthermore, catalytically active Src promotes dynamin-Pyk2 association, and mutating specific Src-phosphorylated tyrosine residues in dynamin blunts the dynamin-induced decrease in Pyk2 phosphorylation. Thus, since Src binds to Pyk2 through its interaction with phospho-Y402, our results suggest that Src activates a negative-feedback loop downstream of integrin engagement and other stimuli by promoting both the binding of dynamin to Pyk2-containing complexes and the dynamin-dependent decrease in Pyk2 Y402 phosphorylation, ultimately leading to the dissociation of Src from Pyk2. PMID:19380485

  2. Dynamin Reduces Pyk2 Y402 Phosphorylation and Src Binding in Osteoclasts ▿ †

    PubMed Central

    Bruzzaniti, Angela; Neff, Lynn; Sandoval, Amanda; Du, Liping; Horne, William C.; Baron, Roland

    2009-01-01

    Signaling via the Pyk2-Src-Cbl complex downstream of integrins contributes to the assembly, organization, and dynamics of podosomes, which are the transient adhesion complexes of highly motile cells such as osteoclasts and dendritic cells. We previously demonstrated that the GTPase dynamin is associated with podosomes, regulates actin flux in podosomes, and promotes bone resorption by osteoclasts. We report here that dynamin associates with Pyk2, independent of dynamin's GTPase activity, and reduces Pyk2 Y402 phosphorylation in a GTPase-dependent manner, leading to decreased Src binding to Pyk2. Overexpressing dynamin decreased the macrophage colony-stimulating factor- and adhesion-induced phosphorylation of Pyk2 in osteoclastlike cells, suggesting that dynamin is likely to regulate Src-Pyk2 binding downstream of integrins and growth factor receptors with important cellular consequences. Furthermore, catalytically active Src promotes dynamin-Pyk2 association, and mutating specific Src-phosphorylated tyrosine residues in dynamin blunts the dynamin-induced decrease in Pyk2 phosphorylation. Thus, since Src binds to Pyk2 through its interaction with phospho-Y402, our results suggest that Src activates a negative-feedback loop downstream of integrin engagement and other stimuli by promoting both the binding of dynamin to Pyk2-containing complexes and the dynamin-dependent decrease in Pyk2 Y402 phosphorylation, ultimately leading to the dissociation of Src from Pyk2. PMID:19380485

  3. 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. PMID:27306340

  4. Caveolin-1 Regulates the P2Y2 Receptor Signaling in Human 1321N1 Astrocytoma Cells.

    PubMed

    Martinez, Namyr A; Ayala, Alondra M; Martinez, Magdiel; Martinez-Rivera, Freddyson J; Miranda, Jorge D; Silva, Walter I

    2016-06-01

    Damage to the CNS can cause a differential spatio-temporal release of multiple factors, such as nucleotides, ATP and UTP. The latter interact with neuronal and glial nucleotide receptors. The P2Y2 nucleotide receptor (P2Y2R) has gained prominence as a modulator of gliotic responses after CNS injury. Still, the molecular mechanisms underlying these responses in glia are not fully understood. Membrane-raft microdomains, such as caveolae, and their constituent caveolins, modulate receptor signaling in astrocytes; yet, their role in P2Y2R signaling has not been adequately explored. Hence, this study evaluated the role of caveolin-1 (Cav-1) in modulating P2Y2R subcellular distribution and signaling in human 1321N1 astrocytoma cells. Recombinant hP2Y2R expressed in 1321N1 cells and Cav-1 were found to co-fractionate in light-density membrane-raft fractions, co-localize via confocal microscopy, and co-immunoprecipitate. Raft localization was dependent on ATP stimulation and Cav-1 expression. This hP2Y2R/Cav-1 distribution and interaction was confirmed with various cell model systems differing in the expression of both P2Y2R and Cav-1, and shRNA knockdown of Cav-1 expression. Furthermore, shRNA knockdown of Cav-1 expression decreased nucleotide-induced increases in the intracellular Ca(2+) concentration in 1321N1 and C6 glioma cells without altering TRAP-6 and carbachol Ca(2+) responses. In addition, Cav-1 shRNA knockdown also decreased AKT phosphorylation and altered the kinetics of ERK1/2 activation in 1321N1 cells. Our findings strongly suggest that P2Y2R interaction with Cav-1 in membrane-raft caveolae of 1321N1 cells modulates receptor coupling to its downstream signaling machinery. Thus, P2Y2R/Cav-1 interactions represent a novel target for controlling P2Y2R function after CNS injury. PMID:27129210

  5. Refractive Error and Ocular Parameters: Comparison of Two SD-OCT Systems

    PubMed Central

    Ostrin, Lisa A.; Yuzuriha, Jill; Wildsoet, Christine F.

    2015-01-01

    Purpose Spectral domain optical coherence tomography (SD-OCT) was used to examine the influence of refractive error (RE) on foveal retinal and choroidal thicknesses and scleral canal width (SCW). The performance of the Cirrus and Bioptigen SD-OCT instruments was compared in the same eyes. Methods Both eyes of forty healthy human subjects, ages 22 to 38 years, were dilated and imaged, with the Cirrus OCT, using 6 mm 5-line rasters collapsed into one line, one centered on the fovea and one bisecting the optic nerve head. Seventy-two of the same eyes were imaged with the Bioptigen OCT, using 6 mm × 6 mm scans, one centered on the fovea and one on the optic nerve head. Subfoveal retinal and choroidal thicknesses and SCW were measured. Axial lengths (AL) and REs were obtained using an IOLMaster and a Grand Seiko autorefractor, respectively. Results Only right eyes were included in analyses. Spherical equivalent REs ranged from −12.18 to +8.12 D (mean: −3.44 ± 4.06 D), and ALs ranged from 20.56 to 29.17 mm (mean: 24.86 ± 1.91 mm). Myopia was associated with relatively thin choroids at the fovea (p<0.05) but normal retinal thickness. SCW was significantly correlated with AL as measured with the Bioptigen OCT (p<0.05). Retinal and choroidal thicknesses recorded with the Bioptigen OCT tended to be smaller than values obtained with the Cirrus OCT (mean difference: 5.63 and 24.76 µm, respectively), while the converse was true for the SCW (mean difference: 25.45 µm). Conclusions The finding that high myopes tend to have a thinner subfoveal choroid is consistent with previous studies. That high myopia was linked to enlarged scleral canals may help to explain the increased risk of glaucoma in myopia. Observed differences obtained with the Cirrus and Bioptigen instruments urge caution in comparing results collected with different instruments. PMID:25785537

  6. Intravenous Toxicity Study of Water-soluble Ginseng Pharmacopuncture in SD Rats

    PubMed Central

    Yu, Jun-Sang; Sun, Seung-Ho; Lee, Kwang-Ho; Kwon, Ki-Rok

    2015-01-01

    Objectives: Radix Ginseng has been used for thousands of years to treat a wide variety of diseases. Radix ginseng has also been used as a traditional medicine for boosting Qi energy and tonifying the spleen and lungs. Traditionally, its effect could be obtained orally. Nowadays, a new method, the injection of herbal medicine, is being used. This study was performed to investigate the single-dose intravenous toxicity of water-soluble ginseng pharmacopuncture (WSGP) in Sprague-Dawley (SD) rats. Methods: All experiments were carried out at Biotoxtech, an institute authorized to perform non-clinical studies under the regulation of Good Laboratory Practice (GLP). At the age of six weeks, 40 SD rats, 20 male rats and 20 female rats, were allocated into one of 4 groups according to the dosages they would receive. The WSGP was prepared in the Korean Pharmacopuncture Institute under the regulation of Korea-Good Manufacturing Practice (K-GMP). Dosages of WSGP were 0.1, 0.5 and 1.0 mL/animal for the experimental groups, and normal saline was administered to the control group. The rat's general conditions and body weights, the results of their hematological and biochemistry tests, and their necropsy and histopathological findings were investigated to identify the toxicological effect of WSGP injected intravenously. The effect was examined for 14 days after the WSGP injection. This study was performed under the approval of the Institutional Animal Ethics Committee of Biotoxtech. Results: No deaths were found in this single-dose toxicity test on the intravenous injection of WSGP, and no significant changes in the rat's general conditions and body weights, the results on their hematological and biochemistry test, and their necropsy findings were observed during the test. The local area of the injection site showed minial change. The lethal dose was assumed to be over 1.0 mL/animal in both sexes. Conclusion: These results indicate that WSGP is safe at dosages up to 1 m

  7. Diversity of DIS, SD and psi hairpins in HIV-1 isolates of group M: in silico study.

    PubMed

    Zarudnaya, M I; Potyahaylo, A L; Kolomiets, I N; Hovorun, D M

    2007-01-01

    The primary sequence and secondary structure of the region encompassing DIS, SD and psi hairpins in HIV-1 genomic RNAs have been analyzed for 731 group M isolates from NCBI database. The secondary structures have been predicted by the m fold program (M. Zuker). Though the primary sequence of the region studied was found to be highly heterogeneous, this region is folded into DIS, SD and psi hairpins (DIS-, SD- and psi-like hairpins) in 96% of the isolates studied. The phylogenetic analysis showed that the most frequent variants of DIS hairpin (DIS(Lai), DIS(Mal) and DIS(C)) tolerate certain base changes. Particularly, base changes at stem position 23 occur 5 and 33 times more frequently in DIS(Lai) than in DIS(Mal) and DIS(C), respectively, while A insertion at the 5'end of apical loop is tolerated in DIS(Mal) and DIS(C) but not in DIS(Lai). We have revealed that the bottom base pair substitution G-C --> A-U in SD hairpin is highly specific for subtype D isolates. All variants of DIS, SD and psi hairpins found in our database are discussed, systematized and presented in schemes of hypothetical transitions between variants via a single base change. Most variants of DIS and psi hairpins were found to adopt several conformations. PMID:18030736

  8. 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. PMID:23220609

  9. 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.

  10. Neutron Skins and Halo Orbits in the sd and pf Shells.

    PubMed

    Bonnard, J; Lenzi, S M; Zuker, A P

    2016-05-27

    The strong dependence of Coulomb energies on nuclear radii makes it possible to extract the latter from calculations of the former. The resulting estimates of neutron skins indicate that two mechanisms are involved. The first one-isovector monopole polarizability-amounts to noting that when a particle is added to a system it drives the radii of neutrons and protons in different directions, tending to equalize the radii of both fluids independently of the neutron excess. This mechanism is well understood and the Duflo-Zuker (small) neutron skin values derived 14 years ago are consistent with recent measures and estimates. The alternative mechanism involves halo orbits whose huge sizes tend to make the neutron skins larger and have a subtle influence on the radial behavior of sd and pf shell nuclei. In particular, they account for the sudden rise in the isotope shifts of nuclei beyond N=28 and the near constancy of radii in the A=40-56 region. This mechanism, detected here for the first time, is not well understood and may well go beyond the Efimov physics usually associated with halo orbits. PMID:27284653

  11. A search for substellar objects orbiting the sdB eclipsing binary HS 0705+6700

    NASA Astrophysics Data System (ADS)

    Qian, S.-B.; Shi, G.; Zola, S.; Koziel-Wierzbowska, D.; Winiarski, M.; Szymanski, T.; Ogloza, W.; Li, L.-J.; Zhu, L.-Y.; Liu, L.; He, J.-J.; Liao, W.-P.; Zhao, E.-G.; Wang, J.-J.; Zhang, J.; Jiang, L.-Q.

    2013-12-01

    By using 78 newly determined timings of light minima together with those collected from the literature, we analysed the changes in the observed minus calculated (O-C) diagram in HS 0705+6700, a short-period (2.3 h) eclipsing binary that consists of a very hot subdwarf B-type (sdB) star and a very cool fully convective red dwarf. We confirmed the cyclic variation in the O-C and refined the parameters of the circumbinary brown dwarf (reported to orbit the binary system in 2009) by analysing the changes for the light travel time effect that arises from the gravitational influence of the third body. Our results indicate the lower mass limit of the third body to be M3 sin i' = 33.7(±1.6) MJup. This companion would be a brown dwarf if its orbital inclination is larger than 27.7° and it is orbiting the central eclipsing binary with an eccentricity e ˜ 0.2 at a separation of about 3.7(±0.1) au.

  12. 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

  13. Effect and mechanism of Salicornia bigelovii Torr. plant salt on blood pressure in SD rats.

    PubMed

    Zhang, Shumeng; Wei, Mingqian; Cao, Chunjie; Ju, Yaoyao; Deng, Yanqun; Ye, Tianwen; Xia, Zufeng; Chen, Meizhen

    2015-03-01

    In this paper, the effect and mechanism of Salicornia bigelovii Torr. plant salt (SPS) on blood pressure in Sprague Dawley (SD) rats were investigated. The results showed that the edible salt induced hypertension, but the SPS did not. Organ indices and Hematoxylin-Eosin (HE) staining analysis indicated that SPS had a protective effect on the kidney and liver. In comparison with the edible salt-treated group, nitric oxide (NO) content, angiotensin-II (Ang-II) and endothelin-1 (ET-1) levels in the serum of the SPS-treated group had no obvious changes, but serum creatinine concentration significantly decreased. Moreover, superoxide dismutase (SOD) and Na(+)-K(+)-ATPase activity increased while malondialdehyde (MDA) content decreased in the SPS-treated group. In conclusion, a long-term high salt intake could lead to hypertension. SPS, as a salt substitute, could increase the body's antioxidant ability to protect the kidney and liver from the damage caused by a high salt intake and effectively avoid the occurrence of hypertension. PMID:25631641

  14. Risk and Vulnerability Analysis of Satellites Due to MM/SD with PIRAT

    NASA Astrophysics Data System (ADS)

    Kempf, Scott; Schafer, Frank Rudolph, Martin; Welty, Nathan; Donath, Therese; Destefanis, Roberto; Grassi, Lilith; Janovsky, Rolf; Evans, Leanne; Winterboer, Arne

    2013-08-01

    Until recently, the state-of-the-art assessment of the threat posed to spacecraft by micrometeoroids and space debris was limited to the application of ballistic limit equations to the outer hull of a spacecraft. The probability of no penetration (PNP) is acceptable for assessing the risk and vulnerability of manned space mission, however, for unmanned missions, whereby penetrations of the spacecraft exterior do not necessarily constitute satellite or mission failure, these values are overly conservative. The newly developed software tool PIRAT (Particle Impact Risk and Vulnerability Analysis Tool) has been developed based on the Schäfer-Ryan-Lambert (SRL) triple-wall ballistic limit equation (BLE), applicable for various satellite components. As a result, it has become possible to assess the individual failure rates of satellite components. This paper demonstrates the modeling of an example satellite, the performance of a PIRAT analysis and the potential for subsequent design optimizations with respect of micrometeoroid and space debris (MM/SD) impact risk.

  15. Immunologic effects of anti-D (WinRho-SD) in children with immune thrombocytopenic purpura.

    PubMed

    Zimmerman, S A; Malinoski, F J; Ware, R E

    1998-02-01

    Intravenous immunoglobulin (IVIG) is an effective treatment for immune thrombocytopenic purpura (ITP) that induces transient blockade of the reticuloendothelial system (RES) with additional effects including alteration of T lymphocyte subsets and suppression of in vitro T lymphocyte proliferation. As anti-D also is an effective treatment for ITP, we investigated its in vitro and in vivo immunologic effects. The in vitro effects of various agents used in ITP therapy were compared using T lymphocyte proliferation assays. Anti-D caused significantly less inhibition than IVIG or dexamethasone, but non-specific protein was as suppressive as IVIG. Six children with chronic ITP were studied following anti-D administration. Patients received a single dose of anti-D (WinRho-SD, 50 microg/kg i.v. over 5 min) and were studied on day 0, day 7, and 1 month later. Anti-D did not affect T lymphocyte subsets including the T cell receptor variable beta repertoire, in vitro T lymphocyte proliferation to mitogens, recall antigens, or interleukin-2, in vitro IgG synthesis induced by pokeweed mitogen, or T lymphocyte cytokine mRNA levels. We conclude that anti-D has no demonstrable in vitro or in vivo effects on lymphocyte enumeration or function, and therefore likely is effective in the treatment of ITP primarily through RES blockade. PMID:9462545

  16. 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. PMID:23911494

  17. Alpha-cluster spectroscopy in 40Ca and in the sd-shell closure region

    NASA Astrophysics Data System (ADS)

    Reidemeister, G.; Ohkubo, S.; Michel, F.

    1990-01-01

    The low-energy 36(α,α) elastic scattering data of Gaul et al. are analyzed within the frame of the optical model, using energy-independent Woods-Saxon squared or model-independent geometries for the real part of the potential. The optical-model scattering amplitude is decomposed into its barrier and internal wave components to understand the rapid and complicated evolution of the angular distributions with incident energy. The properties of the low-energy bound and quasibound states supported by this potential are compared with those of the states of the deformed 4p-4h rotational band in 40Ca, built on the Jπ=0+, Ex=3.35 MeV state. The possibility of extending this local potential model approach to neighboring nuclei near the sd-shell closure is discussed. A negative-parity band of states with appreciable α-cluster character, starting around the α-particle threshold, is expected to be systematically present in this mass region.

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

    PubMed

    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 5μg/ml significantly reduced the cell death caused by anastrozole (1μM) in HOS (human osteoblast) cells. In addition, our results also highlighted that in female SD rat model, SeNPs (0.25, 0.5, 1mg/kg/day) significantly prevented the decrease in bone density and increase in biochemical markers of bone resorption induced by anastrozole (0.2mg/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 (1mg/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. PMID:23415680

  19. 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. PMID:27555965

  20. 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

  1. 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

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

    PubMed

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

    2016-08-01

    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

  3. 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. PMID:12714300

  4. Aquaporin 4-specific T cells and NMO-IgG cause primary retinal damage in experimental NMO/SD.

    PubMed

    Zeka, Bleranda; Hastermann, Maria; Kaufmann, Nathalie; Schanda, Kathrin; Pende, Marko; Misu, Tatsuro; Rommer, Paulus; Fujihara, Kazuo; Nakashima, Ichiro; Dahle, Charlotte; Leutmezer, Fritz; Reindl, Markus; Lassmann, Hans; Bradl, Monika

    2016-01-01

    Neuromyelitis optica/spectrum disorder (NMO/SD) is a severe, inflammatory disease of the central nervous system (CNS). In the majority of patients, it is associated with the presence of pathogenic serum autoantibodies (the so-called NMO-IgGs) directed against the water channel aquaporin 4 (AQP4), and with the formation of large, astrocyte-destructive lesions in spinal cord and optic nerves. A large number of recent studies using optical coherence tomography (OCT) demonstrated that damage to optic nerves in NMO/SD is also associated with retinal injury, as evidenced by retinal nerve fiber layer (RNFL) thinning and microcystic inner nuclear layer abnormalities. These studies concluded that retinal injury in NMO/SD patients results from secondary neurodegeneration triggered by optic neuritis.However, the eye also contains cells expressing AQP4, i.e., Müller cells and astrocytes in the retina, epithelial cells of the ciliary body, and epithelial cells of the iris, which raised the question whether the eye can also be a primary target in NMO/SD. Here, we addressed this point in experimental NMO/SD (ENMO) induced in Lewis rat by transfer of AQP4268-285-specific T cells and NMO-IgG.We show that these animals show retinitis and subsequent dysfunction/damage of retinal axons and neurons, and that this pathology occurs independently of the action of NMO-IgG. We further show that in the retinae of ENMO animals Müller cell side branches lose AQP4 reactivity, while retinal astrocytes and Müller cell processes in the RNFL/ganglionic cell layers are spared. These changes only occur in the presence of both AQP4268-285-specific T cells and NMO-IgG.Cumulatively, our data show that damage to retinal cells can be a primary event in NMO/SD. PMID:27503347

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

    PubMed

    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

  6. 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

  7. Effect of thermal cycling on ZrO2-Y2O3 thermal barrier coatings

    NASA Technical Reports Server (NTRS)

    Mcdonald, G.; Hendricks, R. C.

    1980-01-01

    A study was made of the comparative life of plasma sprayed ZrO2-Y2O3 thermal barrier coatings on NiCrAlY bond coats on Rene 41 in short (4 min) and long (57 min) thermal cycles to 1040 C in a 0.3 Mach flame. Short cycles greatly reduced the life of the ceramic coating in terms of time at temperature as compared to longer cycles. Appearance of the failed coating indicated compressive failure. Failure occurred at the bond coat-ceramic coat junction. At heating rates greater than 550 kw/sq m, the calculated coating detachment stress was in the range of literature values of coating adhesive/cohesive strength. Methods are discussed for decreasing the effect of high heating rate by avoiding compressive stress.

  8. P2Y2 receptor agonists for the treatment of dry eye disease: a review

    PubMed Central

    Lau, Oliver C F; Samarawickrama, Chameen; Skalicky, Simon E

    2014-01-01

    Recent advances in the understanding of dry eye disease (DED) have revealed previously unexplored targets for drug therapy. One of these drugs is diquafosol, a uridine nucleotide analog that is an agonist of the P2Y2 receptor. Several randomized controlled trials have demonstrated that the application of topical diquafosol significantly improves objective markers of DED such as corneal and conjunctival fluorescein staining and, in some studies, tear film break-up time and Schirmer test scores. However, this has been accompanied by only partial improvement in patient symptoms. Although evidence from the literature is still relatively limited, early studies have suggested that diquafosol has a role in the management of DED. Additional studies would be helpful to delineate how different subgroups of DED respond to diquafosol. The therapeutic combination of diquafosol with other topical agents also warrants further investigation. PMID:24511227

  9. 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

  10. P2X and P2Y receptor signaling in red blood cells

    PubMed Central

    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. PMID:26579528

  11. Electronic structure and dx2-y2-wave superconductivity in FeS

    NASA Astrophysics Data System (ADS)

    Yang, Yang; Wang, Wan-Sheng; Lu, Hong-Yan; Xiang, Yuan-Yuan; Wang, Qiang-Hua

    2016-03-01

    We perform theoretical studies on the newly discovered superconductor FeS. Using density functional theory, we obtain the electronic structure of FeS. Using maximally localized Wannier functions, we obtain an effective tight-binding model with five Fe 3 d orbitals. Based on this model, we investigate, by the unbiased singular-mode functional renormalization group, the superconductivity derived from correlation effects. We find the Hund's rule coupling plays a key role in triggering superconductivity, and the pairing symmetry is dx2-y2 wave (viewed in the unfolded zone). The gap function is nodal/nodeless on the hole/electron Fermi pockets, similarly to the case in LaOFeP. The nodal gap is in agreement with experiments.

  12. P2Y12 receptor inhibition and LPS-induced coagulation.

    PubMed

    Essex, David W; Rao, A Koneti

    2016-03-01

    Platelets play a major role in the complex interactions involved in blood coagulation via multiple mechanisms. As reported in this issue, Schoergenhofer et al. tested the hypothesis that platelet inhibition by prasugrel, a potent platelet P2Y12 ADP receptor antagonist, attenuates the effect of lipopolysaccharide (LPS) on the blood coagulation system in healthy human subjects. LPS, a bacterial product with potent pro-inflammatory and pro-thrombotic effects, plays a central role in sepsis. It activates monocytes and endothelial cells via Toll-like receptor (TLR) 4 and other TLRs to stimulate production of TF and other pro-coagulant molecules, chemokines and cytokines. Treatment with prasugrel did not decrease biomarkers of coagulaion. A better understanding of the relative roles of platelet and coagulation mechanisms in triggering the pro-thrombotic state may lead to more effective antithrombotic strategies. PMID:26846581

  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. 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. PMID:24553865

  15. Mining human genome for novel purinergic P2Y receptors: a sequence analysis and molecular modeling approach.

    PubMed

    Bhatnagar, Sonika; Mishra, Shubhi; Pathak, Ravi

    2011-02-01

    The purinergic P2Y receptors are G-protein coupled receptors (GPCRs) that control many physiological processes by mediating cellular responses to purines, pyrimidines and their analogues. They can be used as potential therapeutic targets in a variety of disease conditions. Therefore, it is critical to identify new members of this family of receptors from the human genome and characterize them for their role in health and disease. In the present work, molecular modeling was carried out for the 21 known P2Y receptors. Binding site analysis was done on the basis of docking and site-directed mutagenesis data. Thus, conserved features of P2Y receptors could be formulated. These features can be used to determine the purinergic nature of potential P2Y receptors in the human genome. We applied this knowledge to human genome GPCR sequences found by sensitive sequence search techniques and identified two orphan receptors, namely GPR34 and GP171 that have all the necessary conserved features of P2Y receptors. PMID:21142848

  16. Characterization of P2X3, P2Y1 and P2Y4 receptors in cultured HEK293-hP2X3 cells and their inhibition by ethanol and trichloroethanol.

    PubMed

    Fischer, Wolfgang; Wirkner, Kerstin; Weber, Marco; Eberts, Christoph; Köles, Laszlo; Reinhardt, Robert; Franke, Heike; Allgaier, Clemens; Gillen, Clemens; Illes, Peter

    2003-05-01

    Membrane currents and changes in the intracellular Ca2+ concentration ([Ca2+]i) were measured in HEK293 cells transfected with the human P2X3 receptor (HEK293-hP2X3). RT-PCR and immunocytochemistry indicated the additional presence of endogenous P2Y1 and to some extent P2Y4 receptors. P2 receptor agonists induced inward currents in HEK293-hP2X3 cells with the rank order of potency alpha,beta-meATP approximately ATP > ADP-beta-S > UTP. A comparable rise in [Ca2+]i was observed after the slow superfusion of ATP, ADP-beta-S and UTP; alpha,beta-meATP was ineffective. These data, in conjunction with results obtained by using the P2 receptor antagonists TNP-ATP, PPADS and MRS2179 indicate that the current response to alpha,beta-meATP is due to P2X3 receptor activation, while the ATP-induced rise in [Ca2+]i is evoked by P2Y1 and P2Y4 receptor activation. TCE depressed the alpha,beta-meATP current in a manner compatible with a non-competitive antagonism. The ATP-induced increase of [Ca2+]i was much less sensitive to the inhibitory effect of TCE than the current response to alpha,beta-meATP. The present study indicates that in HEK293-hP2X3 cells, TCE, but not ethanol, potently inhibits ligand-gated P2X3 receptors and, in addition, moderately interferes with G protein-coupled P2Y1 and P2Y4 receptors. Such an effect may be relevant for the interruption of pain transmission in dorsal root ganglion neurons following ingestion of chloral hydrate or trichloroethylene. PMID:12694404

  17. 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.

  18. Improved Determination of the Atmospheric Parameters of the Pulsating sdB Star Feige 48

    NASA Astrophysics Data System (ADS)

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

    2014-06-01

    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 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.

  19. 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.

  20. Heterologous Expression and Characterization of the Manganese-Oxidizing Protein from Erythrobacter sp. Strain SD21

    PubMed Central

    Nakama, Katherine; Medina, Michael; Lien, Ahn; Ruggieri, Jordan; Collins, Krystle

    2014-01-01

    The manganese (Mn)-oxidizing protein (MopA) from Erythrobacter sp. strain SD21 is part of a unique enzymatic family that is capable of oxidizing soluble Mn(II). This enzyme contains two domains, an animal heme peroxidase domain, which contains the catalytic site, followed by a C-terminal calcium binding domain. Different from the bacterial Mn-oxidizing multicopper oxidase enzymes, little is known about MopA. To gain a better understanding of MopA and its role in Mn(II) oxidation, the 238-kDa full-length protein and a 105-kDa truncated protein containing only the animal heme peroxidase domain were cloned and heterologously expressed in Escherichia coli. Despite having sequence similarity to a peroxidase, hydrogen peroxide did not stimulate activity, nor was activity significantly decreased in the presence of catalase. Both pyrroloquinoline quinone (PQQ) and hemin increased Mn-oxidizing activity, and calcium was required. The Km for Mn(II) of the full-length protein in cell extract was similar to that of the natively expressed protein, but the Km value for the truncated protein in cell extract was approximately 6-fold higher than that of the full-length protein, suggesting that the calcium binding domain may aid in binding Mn(II). Characterization of the heterologously expressed MopA has provided additional insight into the mechanism of bacterial Mn(II) oxidation, which will aid in understanding the role of MopA and Mn oxidation in bioremediation and biogeochemical cycling. PMID:25172859

  1. 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.

  2. Heterologous expression and characterization of the manganese-oxidizing protein from Erythrobacter sp. strain SD21.

    PubMed

    Nakama, Katherine; Medina, Michael; Lien, Ahn; Ruggieri, Jordan; Collins, Krystle; Johnson, Hope A

    2014-11-01

    The manganese (Mn)-oxidizing protein (MopA) from Erythrobacter sp. strain SD21 is part of a unique enzymatic family that is capable of oxidizing soluble Mn(II). This enzyme contains two domains, an animal heme peroxidase domain, which contains the catalytic site, followed by a C-terminal calcium binding domain. Different from the bacterial Mn-oxidizing multicopper oxidase enzymes, little is known about MopA. To gain a better understanding of MopA and its role in Mn(II) oxidation, the 238-kDa full-length protein and a 105-kDa truncated protein containing only the animal heme peroxidase domain were cloned and heterologously expressed in Escherichia coli. Despite having sequence similarity to a peroxidase, hydrogen peroxide did not stimulate activity, nor was activity significantly decreased in the presence of catalase. Both pyrroloquinoline quinone (PQQ) and hemin increased Mn-oxidizing activity, and calcium was required. The Km for Mn(II) of the full-length protein in cell extract was similar to that of the natively expressed protein, but the Km value for the truncated protein in cell extract was approximately 6-fold higher than that of the full-length protein, suggesting that the calcium binding domain may aid in binding Mn(II). Characterization of the heterologously expressed MopA has provided additional insight into the mechanism of bacterial Mn(II) oxidation, which will aid in understanding the role of MopA and Mn oxidation in bioremediation and biogeochemical cycling. PMID:25172859

  3. Identification of endogenous surrogate ligands for human P2Y{sub 12} receptors by in silico and in vitro methods

    SciTech Connect

    Nonaka, Yosuke; Hiramoto, Takeshi; Fujita, Norihisa . E-mail: nori@is.ritsumei.ac.jp

    2005-11-11

    Endogenous ligands acting on a human P2Y{sub 12} receptor, one of the G-protein coupled receptors, were searched by in silico screening against our own database, which contains more than 500 animal metabolites. The in silico screening using the docking software AutoDock resulted in selection of cysteinylleukotrienes (CysLTs) and 5-phosphoribosyl 1-pyrophosphate (PRPP), with high free energy changes, in addition to the known P2Y{sub 12} ligands such as 2MeSADP and ADP. These candidates were subjected to an in vitro Ca{sup 2+} assay using the CHO cells stably expressing P2Y{sub 12}-G{sub 16}{alpha} fusion proteins. We found that CysLTE4 and PRPP acted on the P2Y{sub 12} receptor as agonists with the EC{sub 50} values of 1.3 and 7.8 nM, respectively. Furthermore, we analyzed the phylogenetic relationship of the P2Y, P2Y-like, and CysLT receptors based on sequence alignment followed by evolutionary analyses. The analyses showed that the P2Y{sub 12}, P2Y{sub 13}, P2Y{sub 14}, GPR87, CysLT-1, and CysLT-2 receptors formed a P2Y-related receptor subfamily with common sequence motifs in the transmembrane regions.

  4. 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

  5. 76 FR 58241 - Designation for the Aberdeen, SD; Decatur, IL; Hastings, NE; Fulton, IL; the State of Missouri...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-20

    ..., Federal Register (76 FR 15937), GIPSA requested applications for designation to provide official services... Grain Inspection, Packers and Stockyards Administration Designation for the Aberdeen, SD; Decatur, IL; Hastings, NE; Fulton, IL; the State of Missouri, and the State of South Carolina Areas AGENCY:...

  6. 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. PMID:26716833

  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. 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. PMID:23864545

  9. 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

    2012-08-23

    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. Non denaturing poly acrylamide gel electrophoresis and zymogram elucidated the presence of 30 kda 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. (© 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim). PMID:22914902

  10. HS 2333+3927: A new sdB+dM binary with a large reflection effect

    NASA Astrophysics Data System (ADS)

    Heber, U.; Drechsel, H.; Østensen, R.; Karl, C.; Napiwotzki, R.; Altmann, M.; Cordes, O.; Solheim, J.-E.; Voss, B.; Koester, D.; Folkes, S.

    2004-06-01

    We have discovered periodic light variations (P = 0.1718023 d) in the sdB star HS 2333+3927 in the BVR bands with amplitudes of 0.21, 0.28 and 0.33 mag, respectively. Sinusoidal radial velocity variations at the same period were detected with a semi-amplitude of K1 = 89.6 km s-1, indicating that it is binary system and that the light variations are caused by the reflection effect with no eclipses. A mass function of f(m)= 0.0128 M⊙ has been determined. The analysis of the light curve did not yield a unique solution, mainly because the albedo of the secondary is poorly constrained. Two solutions of equal quality with a high (A2= 1.0) and a low (A2= 0.39) albedo were considered further. Variability of the Balmer line profiles, most notably for Hα, was discovered, probably also caused by the reflection effect. A spectroscopic analysis results in Teff = 36 500 K, log g = 5.70, and log (nHe/nH) = -2.15. These characteristics are typical for sdB stars. Mass-radius relations are derived from the results of the analysis of light and radial-velocity curves. Comparison with the observed mass-radius relation of the sdB star and with that of lower main sequence stars for the companion allows us to discard the high albedo solution, because the resulting mass of the primary and the radius of the secondary would be unreasonably low. From a discussion of evolutionary models we constrain the plausible mass of the sdB to the range between 0.29 M⊙ and 0.47 M⊙. Accordingly, the mass of the secondary is between 0.24 M⊙ and 0.32 M⊙, indicating a spectral type of M3 to M4. HS 2333+3927 is only the sixth sdB+dM system discovered so far. An improved measurement of the gravity and the projected rotational velocity of the sdB star is required to further constrain the masses and to identify the evolutionary state of the sdB star uniquely. Based on observations obtained at the German-Spanish Astronomical Center (DSAZ) at Calar Alto, the Nordic Optical Telescope (NOT) and the Jacobus

  11. 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

  12. High Brightness Picture Technology In SD-P40 Projection TV

    NASA Astrophysics Data System (ADS)

    Hasegawa, Shinichi

    1987-04-01

    Pioneer Electric Company has developed a new generation 40-inch rear projection SD-P40 television, a revolutionary, new television that realizes white peak brightness of 300 ft-I and high contrast. The combination of high brightness and high contrast is made possible primarily by newly developed optical-coupling technology that utilizes newly developed concepts. This new optical coupling technology cools the CRT quite efficiently, making it possible to greatly increase the CRT power input to obtain high brightness and at the same time provides greater reliability than direct view televisions. The new optical-coupling technology also makes it possible to almost completely eliminate the reflectance at the boundaries between the CRT and the lens and air, which gives much higher contrast than previous televisions. Not only does this optical-coupling technology provide high performance, in addition since the liquid coolant it employs functions as a liquid lens, the coupling lens can be designed to a uniform thinness and a small aperture. This greatly reduces the cost of the lens. Our newly developed optical-coupling technology is the ultimate form of cooling for the CRT tubes of projection televisions and coupling with the lens and will become the mainstream technology in the future. It is forecast that other manufacturers will also adopt this type of technology. The optical lens section, which is the heart of a projection television, is a hybrid structure with three aspherical plastic lenses and one glass spherical lens. It has higher performance image formation and greater temperature stability than previous televisions. The plastic lenses are all finished with multi-coating to hold down light loss and maximize transparency. This con-tributes greatly to increasing the brightness for a projection television. Previous 3-tube type projection televisions were bothered by low color uniformity, color shift, and low color rela-tive illumination. This model uses three bends

  13. An Rgd Sequence in the P2y2 Receptor Interacts with αVβ3 Integrins and Is Required for Go-Mediated Signal Transduction

    PubMed Central

    Erb, Laurie; Liu, Jun; Ockerhausen, Jonathan; Kong, Qiongman; Garrad, Richard C.; Griffin, Korey; Neal, Chris; Krugh, Brent; Santiago-Pérez, Laura I.; González, Fernando A.; Gresham, Hattie D.; Turner, John T.; Weisman, Gary A.

    2001-01-01

    The P2Y2 nucleotide receptor (P2Y2R) contains the integrin-binding domain arginine-glycine-aspartic acid (RGD) in its first extracellular loop, raising the possibility that this G protein–coupled receptor interacts directly with an integrin. Binding of a peptide corresponding to the first extracellular loop of the P2Y2R to K562 erythroleukemia cells was inhibited by antibodies against αVβ3/β5 integrins and the integrin-associated thrombospondin receptor, CD47. Immunofluorescence of cells transfected with epitope-tagged P2Y2Rs indicated that αV integrins colocalized 10-fold better with the wild-type P2Y2R than with a mutant P2Y2R in which the RGD sequence was replaced with RGE. Compared with the wild-type P2Y2R, the RGE mutant required 1,000-fold higher agonist concentrations to phosphorylate focal adhesion kinase, activate extracellular signal–regulated kinases, and initiate the PLC-dependent mobilization of intracellular Ca2+. Furthermore, an anti-αV integrin antibody partially inhibited these signaling events mediated by the wild-type P2Y2R. Pertussis toxin, an inhibitor of Gi/o proteins, partially inhibited Ca2+ mobilization mediated by the wild-type P2Y2R, but not by the RGE mutant, suggesting that the RGD sequence is required for P2Y2R-mediated activation of Go, but not Gq. Since CD47 has been shown to associate directly with Gi/o family proteins, these results suggest that interactions between P2Y2Rs, integrins, and CD47 may be important for coupling the P2Y2R to Go. PMID:11331301

  14. The structural evolution of a P2Y-like G-protein-coupled receptor.

    PubMed

    Schulz, Angela; Schöneberg, Torsten

    2003-09-12

    Based on the now available crystallographic data of the G-protein-coupled receptor (GPCR) prototype rhodopsin, many studies have been undertaken to build or verify models of other GPCRs. Here, we mined evolution as an additional source of structural information that may guide GPCR model generation as well as mutagenesis studies. The sequence information of 61 cloned orthologs of a P2Y-like receptor (GPR34) enabled us to identify motifs and residues that are important for maintaining the receptor function. The sequence data were compared with available sequences of 77 rhodopsin orthologs. Under a negative selection mode, only 17% of amino acid residues were preserved during 450 million years of GPR34 evolution. On the contrary, in rhodopsin evolution approximately 43% residues were absolutely conserved between fish and mammals. Despite major differences in their structural conservation, a comparison of structural data suggests that the global arrangement of the transmembrane core of GPR34 orthologs is similar to rhodopsin. The evolutionary approach was further applied to functionally analyze the relevance of common scaffold residues and motifs found in most of the rhodopsin-like GPCRs. Our analysis indicates that, in contrast to other GPCRs, maintaining the unique function of rhodopsin requires a more stringent network of relevant intramolecular constrains. PMID:12835326

  15. 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. PMID:24487286

  16. State of affairs: Design and structure-activity relationships of reversible P2Y12 receptor antagonists.

    PubMed

    Zetterberg, Fredrik; Svensson, Peder

    2016-06-15

    Myocardial infarction and stroke are the most common causes of mortality and morbidity in the developed world. Therefore the search for antiplatelet therapy has been in focus for the last decades, in particular the search for new P2Y12R antagonists. The first P2Y12R drug developed, clopidogrel, is a major success but there is still room for improvement with respect to bleeding profile and non-responders. These liabilities could be due to the fact that clopidogrel is a pro-drug and upon activation binds covalently to the receptor. Therefore a lot of effort has gone into identifying reversible inhibitors. One recent example is ticagrelor, which in clinical studies have been shown to be safer and even reduce rate of death from vascular events as compared head to head with clopidogrel. We here review the medicinal chemistry strategies used in the design of new reversible P2Y12R antagonists. In addition, we also present structure based design studies based on the recently published agonist and antagonist X-ray structures of P2Y12R. PMID:27133596

  17. 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

  18. Southern galaxies. VIII - Surface photometry of the SD spiral NGC 7793

    NASA Astrophysics Data System (ADS)

    de Vaucouleurs, G.; Davoust, E.

    1980-08-01

    Detailed surface photometry in blue light of the SA(s)d galaxy NGC 7793, the faintest of the five major members of the Sculptor group, is obtained from photoelectrically calibrated Mount Stromlo and McDonald photographs. The luminosity distribution is dominated by an exponential disk of effective radius αe = 2'.11 = 1.92 kpc contributing 98.6% of the total luminosity BT = 9.51 ± 0.06. The corrected face-on magnitude BT0 = 9.13 corresponds to MT0 = -18.35 at the revised distance Δ = 3.1 Mpc (Appendix C). The spheroidal component visible only in the vicinity of the nucleus can be represented by an r1/4 law of effective radius rIe = 6".0 = 91 pc and total magnitude BTI = 14.13 or 1.4% of the total luminosity of the galaxy. The position angle of the major axis is 97°, the mean axis ratio is q = b/a = 0.61, and the inclination = 53°. The concentration indices C21 = 1.68 and C32 = 1.48 are consistent with the Sd classification. The integrated colors from UBV aperture photometry are essentially constant at = 0.56 ± 0.02, = -0.07 ± 0.02, the corrected face-on colors are (B - V)T0 = 0.46, (U - B)T0 = -0.15 in close agreement with the colors of M33 and the mean values for type Scd. A decomposition of the disk into an underlying old component and a young arm component shows that 65.570 of the total luminosity comes from the old component which has a corrected central luminosity μcα(0) = 21.06 and an effective radius re = 1'.76 = 1.60 kpc. The neutral H I mass MH = 0.67 × 109 Msun corresponds to a hydrogen-luminosity ratio MH/LB = 0.14 which is less than half the average for the morphological type and luminosity class of NGC 7793. The large number of H ii regions and the strength of the Hα emission in the disk suggest that a large fraction of the hydrogen is ionized. The integrated magnitude of the brightest superassociation (Hodge Nr 20) B, = 16.0 ± 0.1 is derived in Appendix A. The effect of resolution on the apparent peak brightness is illustrated in Appendix B

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

    PubMed

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

    2015-11-27

    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 Ca(2+) 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 [Ca(2+)]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

  20. Deletion of GOLGA2P3Y but not GOLGA2P2Y is a risk factor for oligozoospermia.

    PubMed

    Sen, Sanjukta; Agarwal, Rupesh; Ambulkar, Prafulla; Hinduja, Indira; Zaveri, Kusum; Gokral, Jyotsna; Pal, Asoke; Modi, Deepak

    2016-02-01

    The AZFc locus on the human Y chromosome harbours several multicopy genes, some of which are required for spermatogenesis. It is believed that deletion of one or more copies of these genes is a cause of infertility in some men. GOLGA2LY is one of the genes in the AZFc locus and it exists in two copies, GOLGA2P2Y and GOLGA2P3Y. The involvement of GOLGA2LY gene copy deletions in male infertility, however, is unknown. This study aimed to investigate the association of deletions of GOLGA2P2Y and GOLGA2P3Y gene copies with male infertility and with sperm concentration and motility. The frequency of GOLGA2P3Y deletion was significantly higher in oligozoospermic men compared with normozoospermic men (7.7% versus 1.2%; P = 0.0001), whereas the frequency of GOLGA2P2Y deletion was comparable between oligozoospermic and normozoospermic men (10.3% versus 11.3%). The deletion of GOLGA2P3Y but not GOLGA2P2Y was significantly higher (P = 0.03) in men with gr/gr rearrangements, indicating that GOLGA2P3Y deletions increase the susceptibility of men with gr/gr rearrangements to oligozoospermia. Furthermore, men with GOLGA2P3Y deletion had reduced sperm concentration and motility compared with men without deletion or with deletion of GOLGA2P2Y. These findings indicate GOLGA2P3Y gene copy may be candidate AZFc gene for male infertility. PMID:26655651

  1. Omega-3 Fatty Acid Ethyl Esters do not Improve Clopidogrel Associated P2Y12 Inhibition in Stroke Patients

    PubMed Central

    Li, Ping; Kamal, Haris; Baxter, Melissa; Mehta, Bijal K.

    2015-01-01

    The specific action of omega-3 fatty acid ethyl esters (OFA) in preventing cerebrovascular disease remains unknown, but research has demonstrated multiple possible mechanisms. In addition to altering lipid profiles, OFA may inhibit platelet aggregation. Clopidogrel inhibits platelets via the P2Y12 receptor. OFA may alter clopidogrel-associated platelet-inhibition via a possible combined effect on P2Y12 inhibition. To determine if OFA affects clopidogrel associated P2Y12 platelet receptor inhibition by comparing the percentage of responders in patients with cerebrovascular disease who were taking clopidogrel with or without OFA. We retrospectively reviewed data from adult patients with cerebrovascular disease or cerebral aneurysms and taking clopidogrel, who were seen at a single hospital between March 2010 to September 2011. We included 438 subjects in the study. For the 67 subjects who received loading doses of both clopidogrel and OFA, 71.6% had a P2Y12 inhibition response more than 20%, which is considered a positive response. For the 55 subjects who received just clopidogrel load, 67.2% of subjects were responders. There were 70.4% responders in the 274 subjects who were taking 75 mg of clopidogrel alone at home, and 73.8% responders in the 42 subjects who were taking both clopidogrel and OFA at home. However, these percentage differences were not statistically significant. This study did not find additional P2Y12 platelet inhibition when patients were given OFA, either given as a loading dose or taking it daily. PMID:26294943

  2. 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. PMID:26538146

  3. Fatty Acid Composition of Adipose Tissues in Obese Mice and SD Rats Fed with Isaria sinclairii Powder

    PubMed Central

    Ahn, Mi Young; Seo, Yun Jung; Ji, Sang Deok; Han, Jea Woong; Hwang, Jae Sam; Yun, Eun Young

    2010-01-01

    Isaria sinclairii (Cicada Dongchunghacho) was studied as a potential crude natural food in powdered form. The role of tissue fatty acids in relation to the anti-obesity effects of I. sinclairii (IS) was examined by feeding the powder to SD rats ad libitum at 0, 1.25, 2.5, 5 and 10% (calculated about 8 g/kg) of the feed for a period of 3 months and 6 months. The fatty acid composition profile as indicated GC-MS, showed significantly slight dose-dependent increases in the levels of unsaturated fatty acids, particularly, arachidonic acid (C20: 4n6) , oleic acid, linoleic acid, eicosadienoic acid, eicosapentaenoic acid (EPA) (C20: 5) concentration in the the ad libitum IS-fed groups compared to the control group in SD abdominal fat over 6 month period. Over viewing of the SD and Ob mice treated Isaria sinclairii powder; there were increases in the single (mono) unsaturated fatty acids ratio but decreases in polyunsaturated fatty acid. In IS-fed groups in proportion to the treatment period, this Dongchunghacho also induced an increase in the level of same result of unsaturated fatty acid in C57BL/6 obese (ob/ob) mice over a 6-month period treatment compared to those given 10% dry mulberry leaf powder (ML) or silkworm powder mixed with the standard diet. PMID:24278523

  4. INSIGHT INTO THE MODE OF ACTION OF THE LRRK2 Y1699C PATHOGENIC MUTANT

    PubMed Central

    Daniëls, Veronique; Vancraenenbroeck, Renée; Law, Bernard MH; Greggio, Elisa; Lobbestael, Evy; Gao, Fangye; De Maeyer, Marc; Cookson, Mark R; Harvey, Kirsten; Baekelandt, Veerle; Taymans, Jean-Marc

    2010-01-01

    Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most prevalent known cause of autosomal dominant Parkinson's disease (PD). The LRRK2 gene encodes a Roco protein featuring a ROC GTPase and a kinase domain linked by the C-terminal of ROC (COR) domain. Here, we explored the effects of the Y1699C pathogenic LRRK2 mutation in the COR domain on GTPase activity and interactions within the catalytic core of LRRK2. We observed a decrease in GTPase activity for LRRK2 Y1699C comparable to the decrease observed for the R1441C pathogenic mutant and the T1348N dysfunctional mutant. To study the underlying mechanism, we explored the dimerization in the catalytic core of LRRK2. ROC-COR dimerization was significantly weakened by the Y1699C or R1441C/G mutation. Using a competition assay we demonstrated that the intra-molecular ROC:COR interaction is favoured over ROC:ROC dimerization. Interestingly, the intra-molecular ROC:COR interaction was strengthened by the Y1699C mutation. This is supported by a 3D homology model of the ROC-COR tandem of LRRK2, showing that Y1699 is positioned at the intra-molecular ROC:COR interface. In conclusion, our data provides mechanistic insight into the mode of action of the Y1699C LRRK2 mutant: the Y1699C substitution, situated at the intra-molecular ROC:COR interface, strengthens the intra-molecular ROC:COR interaction, thereby locally weakening the dimerization of LRRK2 at the ROC-COR tandem domain resulting in decreased GTPase activity. PMID:21073465

  5. Dehydroepiandrosterone replacement therapy in older adults: 1- and 2-y effects on bone123

    PubMed Central

    Weiss, Edward P; Shah, Krupa; Fontana, Luigi; Lambert, Charles P; Holloszy, John O; Villareal, Dennis T

    2009-01-01

    Background: Age-related reductions in serum dehydroepiandrosterone (DHEA) concentrations may be involved in bone mineral density (BMD) losses. Objective: The objective was to determine whether DHEA supplementation in older adults improves BMD when co-administered with vitamin D and calcium. Design: In year 1, a randomized trial was conducted in which men (n = 55) and women (n = 58) aged 65–75 y took 50 mg/d oral DHEA supplements or placebo. In year 2, all participants took open-label DHEA (50 mg/d). During both years, all participants received vitamin D (16 μg/d) and calcium (700 mg/d) supplements. BMD was measured by using dual-energy X-ray absorptiometry. Concentrations of hormones and bone turnover markers were measured in serum. Results: In men, no difference between groups occurred in any BMD measures or in bone turnover markers during year 1 or year 2. The free testosterone index and estradiol increased in the DHEA group only. In women, spine BMD increased by 1.7 ± 0.6% (P = 0.0003) during year 1 and by 3.6 ± 0.7% after 2 y of supplementation in the DHEA group; however, in the placebo group, spine BMD was unchanged during year 1 but increased to 2.6 ± 0.9% above baseline during year 2 after the crossover to DHEA. Hip BMD did not change. Testosterone, estradiol, and insulin-like growth factor 1 increased in the DHEA group only. In both groups, serum concentrations of bone turnover markers decreased during year 1 and remained low during year 2, but did not differ between groups. Conclusion: DHEA supplementation in older women, but not in men, improves spine BMD when co-administered with vitamin D and calcium. This trial was registered at clinicaltrials.gov as NCT00182975. PMID:19321570

  6. 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

  7. Structure - property relationship of permutite-like amorphous silicates, Nax+2yM3+xSi1-xO2+y(M3+= Al, Mn, Fe, Y), for ion-exchange reactions.

    SciTech Connect

    Pless, Jason D.; Nenoff, Tina Maria; Maxwell, Robert S.; Phillips, Mark L. F.; Axness, Marlene

    2005-03-01

    A series of amorphous silicate materials with the general formula Na{sub x+2y}M{sub x}{sup 3+}Si{sub 1-x}O{sub 2+y}(M{sup 3+} = Al, Mn, Fe, Y) were studied. Samples were synthesized by a precipitation reaction at room temperature. The results indicate that the ion-exchange capacity (IEC) decreases as follows: Al > Fe > Mn > Y. Additionally, the IEC increases with increasing aluminum concentration. Structural studies show that the relative amount of octahedrally coordinated aluminum increases with increasing Al content, as does the total amount of AlO{sub 4} species increases. The data suggest that the IEC value of these amorphous aluminosilicates is dependent on the tetrahedrally coordinated aluminum. Regeneration of the Al-silicate with acetic acid does not decrease the IEC significantly.

  8. P2Y2 receptor activation decreases blood pressure via intermediate conductance potassium channels and connexin 37

    PubMed Central

    Dominguez Rieg, J. A.; Burt, J. M.; Ruth, P.; Rieg, T.

    2015-01-01

    Aims Nucleotides are important paracrine regulators of vascular tone. We previously demonstrated that activation of P2Y2 receptors causes an acute, NO-independent decrease in blood pressure, indicating this signalling pathway requires an endothelial-derived hyperpolarization (EDH) response. To define the mechanisms by which activation of P2Y2 receptors initiates EDH and vasodilation, we studied intermediate-conductance (KCa3.1, expressed in endothelial cells) and big-conductance potassium channels (KCa1.1, expressed in smooth muscle cells) as well as components of the myoendothelial gap junction, connexins 37 and 40 (Cx37, Cx40), all hypothesized to be part of the EDH response. Methods We compared the effects of a P2Y2/4 receptor agonist in wild-type (WT) mice and in mice lacking KCa3.1, KCa1.1, Cx37 or Cx40 under anaesthesia, while monitoring intra-arterial blood pressure and heart rate. Results Acute activation of P2Y2/4 receptors (0.01–3 mg kg−1 body weight i.v.) caused a biphasic blood pressure response characterized by a dose-dependent and rapid decrease in blood pressure in WT (maximal response % of baseline at 3 mg kg−1: −38 ± 1%) followed by a consecutive increase in blood pressure (+44 ± 11%). The maximal responses in KCa3.1−/− and Cx37−/− were impaired (−13 ± 5, +17 ± 7 and −27 ± 1, +13 ± 3% respectively), whereas the maximal blood pressure decrease in response to acetylcholine at 3 µg kg−1 was not significantly different (WT: −53 ± 3%; KCa3.1−/−: −52 ± 3; Cx37−/−: −53 ± 3%). KCa1.1−/− and Cx40−/− showed an identical biphasic response to P2Y2/4 receptor activation compared to WT. Conclusions The data suggest that the P2Y2/4 receptor activation elicits blood pressure responses via distinct mechanisms involving KCa3.1 and Cx37. PMID:25545736

  9. Clopidogrel and ticlopidine: P2Y12 adenosine diphosphate-receptor antagonists for the prevention of atherothrombosis.

    PubMed

    Savi, Pierre; Herbert, Jean-Marc

    2005-04-01

    Ticlopidine and clopidogrel belong to the same chemical family of thienopyridine adenosine diphosphate (ADP)-receptor antagonists. They have shown their efficacy as platelet antiaggregant and antithrombotic agents in many animal models, both ex vivo and in vivo. Although ticlopidine was discovered more than 30 years ago, it was only recently that the mechanism of action of ADP-receptor antagonists was characterized in detail. Ticlopidine and clopidogrel both behave in vivo as specific antagonists of P2Y (12), one of the ADP receptors on platelets. Metabolic steps that involve cytochrome P450-dependent pathways are required to generate the active metabolite responsible for this in vivo activity. The active moiety is a reactive thiol derivative that targets P2Y (12) on platelets. The interaction is irreversible, accounting for the observation that platelets are definitely antiaggregated, even if no active metabolite is detectable in plasma. The interaction is specific for P2Y (12); other purinoceptors such as P2Y (1) and P2Y (13) are spared. This results in inhibition of the binding of the P2Y (12) agonist 2-methylthio-ADP and the ADP-induced downregulation of adenylyl cyclase. Platelet aggregation is affected not only when triggered by ADP but also by aggregation inducers when used at concentrations requiring released ADP as an amplifier. The efficacy and safety of clopidogrel has been established in several large, randomized, controlled trials. The clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE) trial demonstrated the superiority of clopidogrel over acetylsalicylic acid (ASA) in patients at risk of ischemic events, including ischemic stroke, myocardial infarction (MI), and peripheral arterial disease. The clopidogrel in unstable angina to prevent recurrent ischemic events (CURE) trial showed a sustained, incremental benefit when clopidogrel was added to standard therapy (including ASA) in patients with unstable angina and non-Q-wave MI

  10. Autocrine regulation of macrophage activation via exocytosis of ATP and activation of P2Y11 receptor.

    PubMed

    Sakaki, Hayato; Tsukimoto, Mitsutoshi; Harada, Hitoshi; Moriyama, Yoshinori; Kojima, Shuji

    2013-01-01

    It is important to understand the mechanisms that regulate macrophage activation to establish novel therapies for inflammatory diseases, such as sepsis; a systemic inflammatory response syndrome generally caused by bacterial lipopolysaccharide (LPS). In this study, we investigated the involvement of extracellular ATP-mediated autocrine signaling in LPS-induced macrophage activation. We show here that ATP release via exocytosis, followed by activation of P2Y11 receptor, is a major pathway of the macrophage activation, leading to release of cytokines. Treatment of human monocyte THP-1 cells with LPS induced rapid ATP release from cells, and this release was blocked by knockdown of SLC17A9 (vesicular nucleotide transporter, VNUT), which is responsible for exocytosis of ATP. ATP-enriched vesicles were found in cytosol of THP-1 cells. These data suggest the involvement of vesicular exocytosis in the release of ATP. Knockdown of SLC17A9, the P2Y11 antagonist NF157 or knockdown of P2Y11 receptor significantly suppressed both M1-type polarization and IL-6 production in THP-1 cells, indicating an important role of activation of P2Y11 receptor by released ATP in macrophage activation. Next, the effect of NF157 on LPS-induced immune activation was examined in vivo. Administration of LPS to mice caused increase of serum IL-1ß, IL-6, IL-12 and TNF-alpha levels at 3-24 h after the administration. Pre-treatment of LPS-treated mice with NF157 suppressed both elevation of proinflammatory cytokines in serum and M1 polarization of peritoneal/spleen macrophages. Moreover, post-treatment with NF157 at 30 min after administration of LPS also suppressed the elevation of serum cytokines levels. We conclude that vesicular exocytosis of ATP and autocrine, positive feedback through P2Y11 receptors is required for the effective activation of macrophages. Consequently, P2Y11 receptor antagonists may be drug candidates for treatment of inflammatory diseases such as sepsis. PMID:23577075

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

    PubMed

    Junker, Anna; Balasubramanian, Ramachandran; Ciancetta, Antonella; Uliassi, Elisa; Kiselev, Evgeny; Martiriggiano, Chiara; Trujillo, Kevin; Mtchedlidze, Giorgi; Birdwell, Leah; Brown, Kyle A; Harden, T Kendall; Jacobson, Kenneth A

    2016-07-14

    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

  12. 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

  13. Protein Interacting C-Kinase 1 Modulates Surface Expression of P2Y6 Purinoreceptor, Actin Polymerization and Phagocytosis in Microglia.

    PubMed

    Zhu, Jia; Wang, Zhen; Zhang, Nan; Ma, Jiao; Xu, Shui-Lin; Wang, Yin; Shen, Ying; Li, Yun-Hong

    2016-04-01

    Microglia clean up dead cells and debris through phagocytosis in the central nervous system. UDP-activated P2Y6 receptors (P2Y6Rs) induce the formation of phagocytic cup-like structure and P2Y6R expression is increased during the phagocytosis. However, it remains unclear how surface expression of P2Y6R is increased. PICK1 (protein interacting with C-kinase-1) interacts with various neurotransmitter receptors, transporters, and enzymes. We here report that PICK1 might interact with P2Y6R. Surface P2Y6R was reduced in microglia from PICK1-knockout mice and PICK1-knockdown BV2 cells, which was also confirmed by electrophysiological recordings, showing that P2Y6R-mediated current was increased by PICK1 overexpression but was reduced by PICK1-knockdown in BV2 microglia. Finally, PICK1 was sufficient to affect cytoskeletal aggregation and phagocytosis both in primary microglia and BV2 cells. These results indicate that PICK1 is an important regulator of P2Y6R expression and microglial phagocytosis. PMID:26566795

  14. 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...

  15. Efficient removal of toluene and benzene in gas phase by the TiO2/Y-zeolite hybrid photocatalyst.

    PubMed

    Takeuchi, Masato; Hidaka, Manabu; Anpo, Masakazu

    2012-10-30

    Efficient removal of toluene or benzene molecules thinly diffused in gas phase was achieved by using TiO(2)/Y-zeolite hybrid photocatalysts. TiO(2) of 10 wt% hybridized with a hydrophobic USY zeolite showed higher photocatalytic reactivity as compared to TiO(2) hybridized with hydrophilic H-Y or Na-Y zeolites. This phenomenon can be explained by the fact that the hydrophobic USY zeolite efficiently adsorbs the organic compounds and smoothly supplies them onto the TiO(2) photocatalyst surface. However, the toluene or benzene molecules, which are strongly trapped on the hydrophilic H(+) or Na(+) sites of zeolite, cannot diffuse onto the TiO(2) surfaces, resulting in lower photocatalytic reactivity. Although the adsorption capacity of the pure TiO(2) sample rapidly deteriorated, the TiO(2)/Y-zeolite hybrid system maintained a high adsorption efficiency to remove such aromatic compounds for a long period. PMID:22947182

  16. 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.

  17. Exploring a 2-Naphthoic Acid Template for the Structure-Based Design of P2Y14 Receptor Antagonist Molecular Probes

    PubMed Central

    2015-01-01

    The P2Y14 receptor (P2Y14R), one of eight P2Y G protein-coupled receptors (GPCR), is involved in inflammatory, endocrine, and hypoxic processes and is an attractive pharmaceutical target. The goal of this research is to develop high-affinity P2Y14R fluorescent probes based on the potent and highly selective antagonist 4-(4-(piperidin-4-yl)-phenyl)-7-(4-(trifluoromethyl)-phenyl)-2-naphthoic acid (6, PPTN). A model of hP2Y14R based on recent hP2Y12R X-ray structures together with simulated antagonist docking suggested that the piperidine ring is suitable for fluorophore conjugation while preserving affinity. Chain-elongated alkynyl or amino derivatives of 6 for click or amide coupling were synthesized, and their antagonist activities were measured in hP2Y14R-expressing CHO cells. Moreover, a new Alexa Fluor 488 (AF488) containing derivative 30 (MRS4174, Ki = 80 pM) exhibited exceptionally high affinity, as compared to 13 nM for the alkyne precursor 22. A flow cytometry assay employing 30 as a fluorescent probe was used to quantify specific binding to P2Y14R. Known P2Y receptor ligands inhibited binding of 30 with properties consistent with their previously established receptor selectivities and affinities. These results illustrate that potency in this series of 2-naphthoic acid derivatives can be preserved by chain functionalization, leading to highly potent fluorescent molecular probes for P2Y14R. Such conjugates will be useful tools in expanding the SAR of this receptor, which still lacks chemical diversity in its collective ligands. This approach demonstrates the predictive power of GPCR homology modeling and the relevance of newly determined X-ray structures to GPCR medicinal chemistry. PMID:25299434

  18. Phase separation and neighboring ground states of superconductivity in KxFe2---ySe 2

    NASA Astrophysics Data System (ADS)

    Ryu, Hyejin

    Iron-based superconductor KxFe2-ySe 2 has generated considerable attention having higher critical temperature (~31 K)* than previously reported FeSe series (~8 K) and showing a unique phase separation with Fe vacancy order. We investigate the effect of the chemical substitution to the ground state and report various ground states such as spin glass phase and superconductor-insulator transition (SIT) under high-magnetic field by substitution of Na, Te, and Ni on KxFe2-ySe 2 single crystal. The normal-state in-plane resistivity below Tc and the upper critical field for KxFe2-ySe1.85Te0.15 and K0.50Na0.24Fe2-ySe2 are measured by suppressing superconductivity in pulsed magnetic fields. The normal-state resistivity is found to increase logarithmically as T/T c goes to 0 with decreasing temperature similar to granular superconductors and Cu-based high-Tc superconductors. Our results suggest that SIT may be induced in high magnetic fields, which is related to the intrinsic real space phase separated states. We also present a ground state change of KxFe2-delta-yNiySe2 (0.06≤y≤1.44) single crystal alloys. Small amount of Ni (~ 4%) substitution suppresses superconductivity below 1.8 K and for higher Ni content insulating spin glass magnetic ground state is induced.

  19. ATP induces guinea pig gallbladder smooth muscle excitability via the P2Y4 receptor and COX-1 activity.

    PubMed

    Bartoo, Aaron C; Nelson, Mark T; Mawe, Gary M

    2008-06-01

    The purpose of this study was to elucidate the mechanisms by which ATP increases guinea pig gallbladder smooth muscle (GBSM) excitability. We evaluated changes in membrane potential and action potential (AP) frequency in GBSM by use of intracellular recording. Application of ATP (100 microM) caused membrane depolarization and a significant increase in AP frequency that were not sensitive to block by tetrodotoxin (0.5 microM). The nonselective P2 antagonist, suramin (100 microM), blocked the excitatory response, resulting in decreased AP frequency in the presence of ATP. The excitatory response to ATP was not altered by pyridoxal-phosphate-6-azophenyl-2,4-disulfonic acid (30 microM), a nonselective P2X antagonist. UTP also caused membrane depolarization and increased AP frequency, with a similar dose-response relationship as ATP. RT-PCR demonstrated that the P2Y(4), but not P2Y(2), receptor subtype is expressed in guinea pig gallbladder muscularis. ATP induced excitation was blocked by indomethacin (10 microM) and the cyclooxygenase (COX)-1 inhibitor SC-560 (300 nM), but not the COX-2 inhibitor nimesulide (500 nM). These data suggest that ATP stimulates P2Y(4) receptors within the gallbladder muscularis and, in turn, stimulate prostanoid production via COX-1 leading to increased excitability of GBSM. PMID:18436624

  20. Long-Term P2Y12-Receptor Antagonists in Post-Myocardial Infarction Patients: Facing a New Trilemma?

    PubMed

    Alexopoulos, Dimitrios; Xanthopoulou, Ioanna; Moulias, Athanasios; Lekakis, John

    2016-09-13

    Physicians considering prescription of P2Y12-receptor antagonist for long-term (>1 year) protection of patients post-myocardial infarction face the trilemma of selecting between clopidogrel, prasugrel, or ticagrelor. Differential ischemic benefits derived from relevant trials may assist in tailoring treatment, although the different bleeding definitions applied make any meaningful comparison of each agent's bleeding potential very difficult. Considering the available data and recognizing the significant limitation of observations obtained thus far from subgroup analyses, prasugrel appears to provide higher anti-ischemic protection than clopidogrel. Ticagrelor seems to be an attractive option for patients with renal dysfunction, peripheral arterial disease, or following a brief P2Y12-receptor antagonist interruption, whereas clopidogrel may be advised in the presence of cost and availability issues. As head-to-head comparative trials between P2Y12-receptor antagonists are lacking, selection of a specific agent by the clinician should be made on the basis of critical appraisal of available large clinical datasets. PMID:27609686

  1. 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. PMID:24577945

  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. Prenylated indolediketopiperazine peroxides and related homologues from the marine sediment-derived fungus Penicillium brefeldianum SD-273.

    PubMed

    An, Chun-Yan; Li, Xiao-Ming; Li, Chun-Shun; Xu, Gang-Ming; Wang, Bin-Gui

    2014-02-01

    Three new indolediketopiperazine peroxides, namely, 24-hydroxyverruculogen (1), 26-hydroxyverruculogen (2), and 13-O-prenyl-26-hydroxyverruculogen (3), along with four known homologues (4-7), were isolated and identified from the culture extract of the marine sediment-derived fungus Penicillium brefeldianum SD-273. Their structures were determined based on the extensive spectroscopic analysis and compound 1 was confirmed by X-ray crystallographic analysis. The absolute configuration of compounds 1-3 was determined using chiral HPLC analysis of their acidic hydrolysates. Each of the isolated compounds was evaluated for antibacterial and cytotoxic activity as well as brine shrimp (Artemia salina) lethality. PMID:24473173

  4. Complete Nucleotide Sequence of cfr-Carrying IncX4 Plasmid pSD11 from Escherichia coli

    PubMed Central

    Sun, Jian; Deng, Hui; Li, Liang; Chen, Mu-Ya; Fang, Liang-Xing; Yang, Qiu-E

    2014-01-01

    We report the complete nucleotide sequence of a plasmid carrying the multiresistance gene cfr. This plasmid was isolated from an Escherichia coli strain of swine origin in 2011. This 37,672-bp plasmid, pSD11, had an IncX4 backbone similar to those of the IncX4 plasmids obtained from the United States and Australia, in which the cfr gene was flanked by two copies of IS26 and a truncated Tn1331 was inserted. PMID:25403661

  5. Prenylated Indolediketopiperazine Peroxides and Related Homologues from the Marine Sediment-Derived Fungus Penicillium brefeldianum SD-273

    PubMed Central

    An, Chun-Yan; Li, Xiao-Ming; Li, Chun-Shun; Xu, Gang-Ming; Wang, Bin-Gui

    2014-01-01

    Three new indolediketopiperazine peroxides, namely, 24-hydroxyverruculogen (1), 26-hydroxyverruculogen (2), and 13-O-prenyl-26-hydroxyverruculogen (3), along with four known homologues (4–7), were isolated and identified from the culture extract of the marine sediment-derived fungus Penicillium brefeldianum SD-273. Their structures were determined based on the extensive spectroscopic analysis and compound 1 was confirmed by X-ray crystallographic analysis. The absolute configuration of compounds 1–3 was determined using chiral HPLC analysis of their acidic hydrolysates. Each of the isolated compounds was evaluated for antibacterial and cytotoxic activity as well as brine shrimp (Artemia salina) lethality. PMID:24473173

  6. [Metabolomic approach to evaluating the effect of the mixed decoction of kelp and licorice on system metabolism of SD rats].

    PubMed

    Sun, Run-bin; Yu, Xiao-yi; Mao, Yong; Ge, Chun; Yang Na; A, Ji-ye; Tang, Yu-ping; Duan, Jin-ao; Ma, Zi-teng; Wu, Xu-tong; Zhu, Xuan-xuan; Wang, Guang-ji

    2015-03-01

    The aim of the study is to evaluate the effects of the single and mixed decoction of Thallus laminariae (kelp) and Glycyrrhiza glabra (licorice) on the metabolism and their difference. The mixed decoction of kelp and licorice and the single decoction were made and intragastrically administered to the SD rats. The effect on system metabolism, the toxicity of liver and kidney were assessed by GC-MS profiling of the endogenous molecules in serum, routine biochemical assays and histographic inspection of tissues from SD rats, separately. The mixed decoction of kelp and licorice induced more obvious pathological abnormalities in SD rats than a single decoction of kelp, while the extracts of licorice did not show any pathological change. Neither the mixed, nor the single decoction showed abnormal histopathology. After intragastric administration of extracts for 5 days, the mixed decoction induced a decrease of ALT (no significant change in the groups of single decoction) and an increase of BUN (so did the single decoction of kelp). Metabolomic profile of the molecules in serum revealed that the metabolic patterns were all obviously affected for the three groups, i.e., the mixed and single decoction of kelp and licorice. The rats given with the single decoction of kelp showed a similar pattern to that of the mixed decoction, indicating that the kelp primarily contributed the perturbation of metabolism for the mixed decoction. All three groups induced a decrease of branched chain amino acids, TCA cycle intermediates and glycolysis intermediates (e.g., pyruvic acid and lactic acid) and an increase of 3-hydroxybutyric acid. Kelp decoction showed stronger potential in reducing TCA cycle intermediates and glycolysis intermediates than the other two groups, while the levels of branched chain amino acids were the lowest after licorice extracts were given. These results suggested that the effect of the mixed decoction on metabolism was closely associated with both kelp and

  7. 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.

  8. Agonist-selective, Receptor-specific Interaction of Human P2Y Receptors with β-Arrestin-1 and -2*S⃞

    PubMed Central

    Hoffmann, Carsten; Ziegler, Nicole; Reiner, Susanne; Krasel, Cornelius; Lohse, Martin J.

    2008-01-01

    Interaction of G-protein-coupled receptors with β-arrestins is an important step in receptor desensitization and in triggering “alternative” signals. By means of confocal microscopy and fluorescence resonance energy transfer, we have investigated the internalization of the human P2Y receptors 1, 2, 4, 6, 11, and 12 and their interaction with β-arrestin-1 and -2. Co-transfection of each individual P2Y receptor with β-arrestin-1-GFP or β-arrestin-2-YFP into HEK-293 cells and stimulation with the corresponding agonists resulted in a receptor-specific interaction pattern. The P2Y1 receptor stimulated with ADP strongly translocated β-arrestin-2-YFP, whereas only a slight translocation was observed for β-arrestin-1-GFP. The P2Y4 receptor exhibited equally strong translocation for β-arrestin-1-GFP and β-arrestin-2-YFP when stimulated with UTP. The P2Y6, P2Y11, and P2Y12 receptor internalized only when GRK2 was additionally co-transfected, but β-arrestin translocation was only visible for the P2Y6 and P2Y11 receptor. The P2Y2 receptor showed a β-arrestin translocation pattern that was dependent on the agonist used for stimulation. UTP translocated β-arrestin-1-GFP and β-arrestin-2-YFP equally well, whereas ATP translocated β-arrestin-1-GFP to a much lower extent than β-arrestin-2-YFP. The same agonist-dependent pattern was seen in fluorescence resonance energy transfer experiments between the fluorescently labeled P2Y2 receptor and β-arrestins. Thus, the P2Y2 receptor would be classified as a class A receptor when stimulated with ATP or as a class B receptor when stimulated with UTP. The ligand-specific recruitment of β-arrestins by ATP and UTP stimulation of P2Y2 receptors was further found to result in differential stimulation of ERK phosphorylation. This suggests that the two different agonists induce distinct active states of this receptor that show differential interactions with β-arrestins. PMID:18703513

  9. XN2Y-1 Model Being Prepared for Spin Tunnel Tests

    NASA Technical Reports Server (NTRS)

    1935-01-01

    Model of XN2Y-1 biplane mounted on a special test rig to determine moments of inertia prior to spin tests in the Langley 15-Foot Spin Tunnel. This was one of two balsa wood models (the other was a 1/12- scale model of the F4B-2) for initial testing and calibration of the new tunnel. Researchers were very concerned that the results they might achieve with models in the tunnel would not correlate with the spinning behavior of full-scale airplanes. They noted that: 'comparisons between results from the N.A.C.A. spinning balance and full-scale flight tests have indicated considerable scale effect upon aerodynamic characteristics in spinning attitudes.' Thus, these first two models were chosen for testing in the new tunnel because their full-scale spinning characteristics were already well known. These first tests proved encouraging to the researchers but they did not achieve the precise degree of reliability hoped for. The facility's opening however, does signify the advent of a serious and long term commitment to studying the problem of aircraft spinning. From NACA TR No. 557: 'At the beginning of a test the model is mounted upon a launching spindle about the axis of which it is free to rotate. This spindle is on the end of a wooden rod and is held in the center of the tunnel by one of the operators standing in the observation chamber. With the spindle vertical the attitude of the model is such that the fuselage axis is approximately 35L to the horizontal, nose down, and the wings are 10L to the horizontal with the left wing tip the lower (for a right spin). When the model is in this attitude, air flowing upward through the tunnel causes it to rotate fairly rapidly. The air speed is increased by a second operator until the air force on the model is equal to its weight. The model then automatically disengages itself from the spindle and continues to float in the air stream entirely free of mechanical restraint. The launching spindle is immediately withdrawn from the

  10. XN2Y-1 Model Being Prepared for Spin Tunnel Tests

    NASA Technical Reports Server (NTRS)

    1935-01-01

    Model of XN2Y-1 biplane mounted on a special test rig to determine moments of inertia prior to spin tests in the Langley 15-Foot Spin Tunnel. This was one of two balsa wood models (the other was a 1/12- scale model of the F4B-2) for initial testing and calibration of the new tunnel. Researchers were very concerned that the results they might achieve with models in the tunnel would not correlate with the spinning behavior of full-scale airplanes. They noted that: 'comparisons between results from the N.A.C.A. spinning balance and full-scale flight tests have indicated considerable scale effect upon aerodynamic characteristics in spinning attitudes.' Thus, these first two models were chosen for testing in the new tunnel because their full-scale spinning characteristics were already well known. These first tests proved encouraging to the researchers but they did not achieve the precise degree of reliability hoped for. The facility's opening however, does signify the advent of a serious and long term commitment to studying the problem of aircraft spinning. Charles Zimmerman wrote in NACA TR No. 557: 'At the beginning of a test the model is mounted upon a launching spindle about the axis of which it is free to rotate. This spindle is on the end of a wooden rod and is held in the center of the tunnel by one of the operators standing in the observation chamber. With the spindle vertical the attitude of the model is such that the fuselage axis is approximately 35 to the horizontal, nose down, and the wings are 10 to the horizontal with the left wing tip the lower (for a right spin). When the model is in this attitude, air flowing upward through the tunnel causes it to rotate fairly rapidly. The air speed is increased by a second operator until the air force on the model is equal to its weight. The model then automatically disengages itself from the spindle and continues to float in the air stream entirely free of mechanical restraint. The launching spindle is immediately

  11. New ex-ovo colorectal-cancer models from different SdFFF-sorted tumor-initiating cells.

    PubMed

    Mélin, Carole; Perraud, Aurélie; Christou, Niki; Bibes, Romain; Cardot, Philippe; Jauberteau, Marie-Odile; Battu, Serge; Mathonnet, Muriel

    2015-11-01

    Despite effective treatments, relapse of colorectal cancer (CRC) is frequent, in part caused by the existence of tumor-initiating cells (TICs). Different subtypes of TICs, quiescent and activated, coexist in tumors, defining the tumor aggressiveness and therapeutic response. These subtypes have been sorted by hyperlayer sedimentation field-flow fractionation (SdFFF) from WiDr and HCT116 cell lines. On the basis of a new strategy, including TIC SdFFF sorting, 3D Matrigel amplification, and grafting of corresponding TIC colonies on the chick chorioallantoic membrane (CAM), specific tumor matrices could be obtained. If tumors had similar architectural structure with vascularization by the host system, they had different proliferative indices in agreement with their initial quiescent or activated state. Protein analysis also revealed that tumors obtained from a population enriched for "activated" TICs lost "stemness" properties and became invasive. In contrast, tumors obtained from a population enriched for "quiescent" TICs kept their stemness properties and seemed to be less proliferative and invasive. Then, it was possible to produce different kinds of tumor which could be used as selective supports to study carcinogenesis and therapy sensitivity. PMID:26427501

  12. High-resolution spectrometer: solution to the axial resolution and ranging depth trade-off of SD-OCT

    NASA Astrophysics Data System (ADS)

    Marvdashti, Tahereh; Lee, Hee Yoon; Ellerbee, Audrey K.

    2013-03-01

    We demonstrate a cross-dispersed spectrometer for Spectral Domain Optical Coherence Tomography (SD-OCT). The resolution of a conventional SD-OCT spectrometer is limited by the available sizes of the linear array detectors. The adverse consequences of this finite resolution is a trade-off between achieving practical field of view (i.e. ranging depth) and maintaining high axial resolution. Inspired by spectrometer designs for astronomy, we take advantage of very high pixel-density 2D CCD arrays to map a single-shot 2D spectrum to an OCT A-scan. The basic system can be implemented using a high-resolution Echelle grating crossed with a prism in a direction orthogonal to the dispersion axis. In this geometry, the interferometric light returning from the OCT system is dispersed in two dimensions; the resulting spectrum can achieve more pixels than a traditional OCT spectrometer (which increases the ranging depth) and maintains impressive axial resolution because of the broad bandwidth of the detected OCT light. To the best of our knowledge, we present the first demonstration of OCT data using an Echelle-based cross-dispersed spectrometer. Potential applications for such a system include high-resolution imaging of the retina or the anterior segment of the eye over extended imaging depths and small animal imaging.

  13. Activation of P2Y6 receptors increases the voiding frequency in anaesthetized rats by releasing ATP from the bladder urothelium

    PubMed Central

    Carneiro, Inês; Timóteo, M Alexandrina; Silva, Isabel; Vieira, Cátia; Baldaia, Catarina; Ferreirinha, Fátima; Silva-Ramos, Miguel; Correia-de-Sá, Paulo

    2014-01-01

    BACKGROUND AND PURPOSE Despite the abundant expression of the UDP-sensitive P2Y6 receptor in urothelial cells and sub-urothelial myofibroblasts its role in the control of bladder function is not well understood. EXPERIMENTAL APPROACH We compared the effects of UDP and of the selective P2Y6 receptor agonist, PSB0474, on bladder urodynamics in anaesthetized rats; the voided fluid was tested for ATP bioluminescence. The isolated urinary bladder was used for in vitro myographic recordings and [3H]-ACh overflow experiments. KEY RESULTS Instillation of UDP or PSB0474 into the bladder increased the voiding frequency (VF) without affecting the amplitude (A) and the duration (Δt) of bladder contractions; an effect blocked by the P2Y6 receptor antagonist, MRS2578. Effects mediated by urothelial P2Y6 receptors required extrinsic neuronal circuitry as they were not detected in the isolated bladder. UDP-induced bladder hyperactvity was also prevented by blocking P2X3 and P2Y1 receptors, respectively, with A317491 and MRS2179 applied i.v.. UDP decreased [3H]-ACh release from stimulated bladder strips with urothelium, but not in its absence. Inhibitory effects of UDP were converted into facilitation by the P2Y1 receptor antagonist, MRS2179. The P2Y6 receptor agonist increased threefold ATP levels in the voided fluid. CONCLUSIONS AND IMPLICATIONS Activation of P2Y6 receptors increased the voiding frequency indirectly by releasing ATP from the urothelium and activation of P2X3 receptors on sub-urothelial nerve afferents. Bladder hyperactivity may be partly reversed following ATP hydrolysis to ADP by E-NTPDases, thereby decreasing ACh release from cholinergic nerves expressing P2Y1 receptors. PMID:24697602

  14. P2Y13 receptor-mediated rapid increase in intracellular calcium induced by ADP in cultured dorsal spinal cord microglia.

    PubMed

    Zeng, Junwei; Wang, Gaoxia; Liu, Xiaohong; Wang, Chunmei; Tian, Hong; Liu, Aidong; Jin, Huan; Luo, Xiaomei; Chen, Yuanshou

    2014-11-01

    P2Y receptors have been implicated in the calcium mobilization by the response to neuroexcitatory substances in neurons and astrocytes, but little is known about P2Y receptors in microglia cells. In the present study, the effects of ADP on the intracellular calcium concentration ([Ca(2+)]i) in cultured dorsal spinal cord microglia were detected with confocal laser scanning microscopy using fluo-4/AM as a calcium fluorescence indicator that could monitor real-time alterations of [Ca(2+)]i. Here we show that ADP (0.01-100 μM) causes a rapid increase in [Ca(2+)]i with a dose-dependent manner in cultured microglia. The action of ADP on [Ca(2+)]i was significantly blocked by MRS2211 (a selective P2Y13 receptor antagonist), but was unaffected by MRS2179 (a selective P2Y1 receptor antagonist) or MRS2395 (a selective P2Y12 receptor antagonist), which suggest that P2Y13 receptor may be responsible for ADP-evoked Ca(2+) mobilization in cultured microglia. P2Y13-evoked Ca(2+) response can be obviously inhibited by BAPTA-AM and U-73122, respectively. Moreover, removal of extracellular Ca(2+) (by EGTA) also can obvious suppress the Ca(2+) mobilization. These results means both intracellular calcium and extracellular calcium are potentially important mechanisms in P2Y13 receptor-evoked Ca(2+) mobilization. However, P2Y13 receptor-evoked Ca(2+) response was not impaired after CdCl2 and verapamil administration, which suggest that voltage-operated Ca(2+) channels may be not related with P2Y13-evoked Ca(2+) response. In addition, Ca(2+) mobilization induced by ADP was abolished by different store-operated Ca(2+) channels (SOCs) blocker, 2-APB (50 μM) and SKF-96365 (1 mM), respectively. These observations suggest that the activation of P2Y13 receptor might be involved in the effect of ADP on [Ca(2+)]i in cultured dorsal spinal cord microglia. Furthermore, our results raise a possibility that P2Y13 receptor activation causes Ca(2+) release from Ca(2+) store, which leads to the

  15. Expression of the P2Y2 receptor in the terminal rectum of fetal rats with anorectal malformation

    PubMed Central

    Liu, Yuan-Mei; Kong, Meng; Jin, Zhu; Gao, Ming-Mei; Qu, Yan; Zheng, Ze-Bing

    2015-01-01

    Objective: The expression and distribution of a subtype of purine receptors (P2Y2) in the terminal rectum of fetal rats with anorectal malformations (ARM) were examined to investigate their possible impact on the development of the enteric nervous system (ENS). Methods: Pregnant Sprague-Dawley rats were randomly divided into a control group (5 rats) and an experimental group (20 rats). The experimental group was treated with ethylene thiourea (ETU). On gestational day 20, the intrauterine fetal rats were collected from both groups of pregnant rats. Sagittal sections of the pelvic perinea were stained with HE. P2Y2 protein and mRNA expression in the terminal recta of the fetal rats in the control group, the ARM group, and the ETU-treated group that exhibited no malformations (the ETU group) were detected by immunohistochemistry, western blot, and qRT-PCR. Results: The fetal rats in the control group showed normal position of the anal opening, with no malformation. The incidence of ARM was 89.2% for the fetal rats in the experimental group. The immunohistochemistry results showed that P2Y2 was expressed in the cytoplasm of the cells in the terminal rectum submucosa and myenteric plexus of the fetus rats in the control group, the ETU group, and the ARM group. The average integrated optical density (IOD) value for the ARM group was significantly lower than the IOD value for the control and ETU groups (186.48 ± 23.03 vs. 493.18 ± 19.70; 186.48 ± 23.03 vs. 479.48 ± 41.71, P<0.01), while the IOD value for the ETU group was comparable to the control group IOD (493.18 ± 19.70 vs. 479.48 ± 41.71, P = 0.360). The western blot and qRT-PCR results showed that the P2Y2 protein and mRNA expressions were significantly lower in the terminal rectum of the fetal rats in the ARM group than in the control and ETU groups (0.28 ± 0.08 vs. 0.51 ± 0.10, 0.28 ± 0.08 vs. 0.48 ± 0.12; 48.91 ± 12.17 vs. 98.03 ± 15.68, 48.91 ± 12.17 vs. 92.53 ± 10.43; P<0.01), while the P2Y2

  16. 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.

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

    PubMed

    Ramirez, Jean Marie; Houzet, Laurent; Koller, Richard; Bies, Juraj; Wolff, Linda; Mougel, Marylène

    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. PMID:15567434

  18. Inhibitory neuromuscular transmission mediated by the P2Y1 purinergic receptor in guinea pig small intestine.

    PubMed

    Wang, Guo-Du; Wang, Xi-Yu; Hu, Hong-Zhen; Liu, Sumei; Gao, Na; Fang, Xiucai; Xia, Yun; Wood, Jackie D

    2007-06-01

    ATP is a putative inhibitory neurotransmitter responsible for inhibitory junction potentials (IJPs) at neuromuscular junctions (IJPs) in the intestine. This study tested the hypothesis that the purinergic P2Y(1) receptor subtype mediates the IJPs. IJPs were evoked by focal electrical stimulation in the myenteric plexus and recorded with "sharp" intracellular microelectrodes in the circular muscle coat. Stimulation evoked three categories of IJPs: 1) purely purinergic IJPs, 2) partially purinergic IJPs, and 3) nonpurinergic IJPs. Purely purinergic IJPs were suppressed by the selective P2Y(1) purinergic receptor antagonist MRS2179. Purely purinergic IJPs comprised 26% of the IJPs. Partially purinergic IJPs (72% of the IJPs) consisted of a component that was abolished by MRS2179 and a second unaffected component. The MRS2179-insensitive component was suppressed or abolished by inhibition of formation of nitric oxide by N(omega)-nitro-l-arginine methyl ester (l-NAME) in some, but not all, IJPs. An unidentified neurotransmitter, different from nitric oxide, mediated the second component in these cases. Nonpurinergic IJPs were a small third category (4%) of IJPs that were abolished by l-NAME and unaffected by MRS2179. Exogenous application of ATP evoked IJP-like hyperpolarizing responses, which were blocked by MRS2179. Application of apamin, which suppresses opening of small-conductance Ca(2+)-operated K(+) channels in the muscle, decreased the amplitude of the purinergic IJPs and the amplitude of IJP-like responses to ATP. The results support ATP as a neurotransmitter for IJPs in the intestine and are consistent with the hypothesis that the P2Y(1) purinergic receptor subtype mediates the action of ATP. PMID:17322065

  19. 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

  20. 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

  1. 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

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

    PubMed

    Koeck, Daniela E; Maus, Irena; Wibberg, Daniel; Winkler, Anika; Zverlov, Vladimir V; Liebl, Wolfgang; Pühler, Alfred; Schwarz, Wolfgang H; Schlüter, Andreas

    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 T3/55(T), indicating a novel species within the genus Herbinix (family Lachnospiraceae). Here, the complete genome sequence of Herbinix luporum SD1D is reported. PMID:27445379

  3. 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.

  4. Critical current density and mechanism of vortex pinning in KxFe2-ySe₂ doped with S

    DOE PAGESBeta

    Lei, Hechang; Petrovic, C.

    2011-08-15

    We report the critical current density Jc in KxFe2-ySe2-zSz crystals. The Jc can be enhanced significantly with optimal S doping (z=0.99). For K0.70(7)Fe1.55(7)Se1.01(2)S0.99(2), the weak fishtail effect is found for H II c. The normalized vortex pinning forces follow the scaling law with a maximum position at 0.41 of the reduced magnetic field. These results demonstrate that the small size normal point defects dominate the vortex pinning mechanism.

  5. NIR to visible upconversion emission in Tm3+ doped Na2Y2B2O7 powder phosphor

    NASA Astrophysics Data System (ADS)

    Soni, Abhishek Kumar; Rai, Vineet Kumar

    2015-05-01

    Tm3+ ions doped Na2Y2B2O7 powder phosphor has been synthesized through combustion method. Crystal structure and phase of the prepared sample have been investigated by powder X-ray diffraction (XRD) analysis. Upconversion emission bands in the 400-900 nm range under the excitation of 980nm diode laser have been acquired, and involved upconversion mechanism has been discussed with the help of a suitable energy level diagram. The colour coordinate of developed phosphor has been calculated by CIE chromaticity diagram. Present phosphor can be used in fabrication of upconverting LEDs.

  6. Synthesis and characterization of a cellular membrane affinity chromatography column containing histamine 1 and P2Y1 receptors: A multiple G-protein coupled receptor column

    PubMed Central

    Moaddel, Ruin; Musyimi, Harrison K.; Sanghvi, Mitesh; Bashore, Charlene; Frazier, Chester R.; Khadeer, Mohammad; Bhatia, Prateek; Wainer, Irving W.

    2015-01-01

    A cellular membrane affinity chromatography (CMAC) column has been created using cellular membrane fragments from a 1321N1 cell line stably transfected with the P2Y1 receptor. The CMAC(1321N1P2Y1) column contained functional P2Y1 and histamine 1 receptors, which independently bound receptor-specific ligands. The data obtained with the CMAC(1321N1P2Y1) column demonstrate that multiple-G-protein coupled receptor (GPCR) columns can be developed and used to probe interactions with the immobilized receptors and that endogenously expressed GPCRs can be used to create CMAC columns. The results also establish that the histamine 1 receptor can be immobilized with retention of ligand-specific binding. PMID:19608372

  7. Differential effects of P2Y1 deletion on glial activation and survival of photoreceptors and amacrine cells in the ischemic mouse retina

    PubMed Central

    Pannicke, T; Frommherz, I; Biedermann, B; Wagner, L; Sauer, K; Ulbricht, E; Härtig, W; Krügel, U; Ueberham, U; Arendt, T; Illes, P; Bringmann, A; Reichenbach, A; Grosche, A

    2014-01-01

    Gliosis of retinal Müller glial cells may have both beneficial and detrimental effects on neurons. To investigate the role of purinergic signaling in ischemia-induced reactive gliosis, transient retinal ischemia was evoked by elevation of the intraocular pressure in wild-type (Wt) mice and in mice deficient in the glia-specific nucleotide receptor P2Y1 (P2Y1 receptor-deficient (P2Y1R-KO)). While control retinae of P2Y1R-KO mice displayed reduced cell numbers in the ganglion cell and inner nuclear layers, ischemia induced apoptotic death of cells in all retinal layers in both, Wt and P2Y1R-KO mice, but the damage especially on photoreceptors was more pronounced in retinae of P2Y1R-KO mice. In contrast, gene expression profiling and histological data suggest an increased survival of amacrine cells in the postischemic retina of P2Y1R-KO mice. Interestingly, measuring the ischemia-induced downregulation of inwardly rectifying potassium channel (Kir)-mediated K+ currents as an indicator, reactive Müller cell gliosis was found to be weaker in P2Y1R-KO (current amplitude decreased by 18%) than in Wt mice (decrease by 68%). The inner retina harbors those neurons generating action potentials, which strongly rely on an intact ion homeostasis. This may explain why especially these cells appear to benefit from the preserved Kir4.1 expression in Müller cells, which should allow them to keep up their function in the context of spatial buffering of potassium. Especially under ischemic conditions, maintenance of this Müller cell function may dampen cytotoxic neuronal hyperexcitation and subsequent neuronal cell loss. In sum, we found that purinergic signaling modulates the gliotic activation pattern of Müller glia and lack of P2Y1 has janus-faced effects. In the end, the differential effects of a disrupted P2Y1 signaling onto neuronal survival in the ischemic retina call the putative therapeutical use of P2Y1-antagonists into question. PMID:25077539

  8. Differential effects of P2Y1 deletion on glial activation and survival of photoreceptors and amacrine cells in the ischemic mouse retina.

    PubMed

    Pannicke, T; Frommherz, I; Biedermann, B; Wagner, L; Sauer, K; Ulbricht, E; Härtig, W; Krügel, U; Ueberham, U; Arendt, T; Illes, P; Bringmann, A; Reichenbach, A; Grosche, A

    2014-01-01

    Gliosis of retinal Müller glial cells may have both beneficial and detrimental effects on neurons. To investigate the role of purinergic signaling in ischemia-induced reactive gliosis, transient retinal ischemia was evoked by elevation of the intraocular pressure in wild-type (Wt) mice and in mice deficient in the glia-specific nucleotide receptor P2Y1 (P2Y1 receptor-deficient (P2Y1R-KO)). While control retinae of P2Y1R-KO mice displayed reduced cell numbers in the ganglion cell and inner nuclear layers, ischemia induced apoptotic death of cells in all retinal layers in both, Wt and P2Y1R-KO mice, but the damage especially on photoreceptors was more pronounced in retinae of P2Y1R-KO mice. In contrast, gene expression profiling and histological data suggest an increased survival of amacrine cells in the postischemic retina of P2Y1R-KO mice. Interestingly, measuring the ischemia-induced downregulation of inwardly rectifying potassium channel (Kir)-mediated K(+) currents as an indicator, reactive Müller cell gliosis was found to be weaker in P2Y1R-KO (current amplitude decreased by 18%) than in Wt mice (decrease by 68%). The inner retina harbors those neurons generating action potentials, which strongly rely on an intact ion homeostasis. This may explain why especially these cells appear to benefit from the preserved Kir4.1 expression in Müller cells, which should allow them to keep up their function in the context of spatial buffering of potassium. Especially under ischemic conditions, maintenance of this Müller cell function may dampen cytotoxic neuronal hyperexcitation and subsequent neuronal cell loss. In sum, we found that purinergic signaling modulates the gliotic activation pattern of Müller glia and lack of P2Y1 has janus-faced effects. In the end, the differential effects of a disrupted P2Y1 signaling onto neuronal survival in the ischemic retina call the putative therapeutical use of P2Y1-antagonists into question. PMID:25077539

  9. The sexually dimorphic on the Y-chromosome gene (sdY) is a conserved male-specific Y-chromosome sequence in many salmonids

    PubMed Central

    Yano, Ayaka; Nicol, Barbara; Jouanno, Elodie; Quillet, Edwige; Fostier, Alexis; Guyomard, René; Guiguen, Yann

    2013-01-01

    All salmonid species investigated to date have been characterized with a male heterogametic sex-determination system. However, as these species do not share any Y-chromosome conserved synteny, there remains a debate on whether they share a common master sex-determining gene. In this study, we investigated the extent of conservation and evolution of the rainbow trout (Oncorhynchus mykiss) master sex-determining gene, sdY (sexually dimorphic on the Y-chromosome), in 15 different species of salmonids. We found that the sdY sequence is highly conserved in all salmonids and that sdY is a male-specific Y-chromosome gene in the majority of these species. These findings demonstrate that most salmonids share a conserved sex-determining locus and also strongly suggest that sdY may be this conserved master sex-determining gene. However, in two whitefish species (subfamily Coregoninae), sdY was found both in males and females, suggesting that alternative sex-determination systems may have also evolved in this family. Based on the wide conservation of sdY as a male-specific Y-chromosome gene, efficient and easy molecular sexing techniques can now be developed that will be of great interest for studying these economically and environmentally important species. PMID:23745140

  10. OD(X/sup 2/II) and SD(X/sup 2/II) from reactions of D atoms with OCS under bulk and precursor geometry limited conditions

    SciTech Connect

    Haeusler, D.; Rice, J.; Wittig, C.

    1987-10-08

    Reactions of D atoms with OCS were studied by 193-nm pulsed laser photolysis of DBr as a nearly monoenergetic D-atom source. Nascent OD(X/sup 2/II) and SD(X/sup 2/II) rotational, vibrational, spin-orbit, and ..lambda..-doublet populations were obtained under single-collision bulk conditions at 300 K. The SD channel is favored energetically (..delta.. H = -43 +/- 13 and 230 +/- 13 kJ mol/sup -1/ for the SD and OD channels, respectively) and is the dominant pathway ((SD)/(OD) = 5 +/- 2). Nascent OD(X/sup 2/II) products were also obtained from a precursor geometry limited (PGL) reaction by using the weakly bound van der Waals complex SCO-DBr. The OD(X/sup 2/II) rotational distributions are the same for both bulk and PGL conditions and can be reproduced by using a statistical model. Due to experimental difficulties, SD(X/sup 2/II) distributions could not be obtained under PGL conditions. The SD(X/sup 2/II) distribution obtained under bulk conditions is very nonstatistical, suggesting that this species is not formed via a long-lived DSCO intermediate complex in which vibrational energy is randomized.

  11. 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).

  12. Analysis of Genes for Succinoyl Trehalose Lipid Production and Increasing Production in Rhodococcus sp. Strain SD-74

    PubMed Central

    Inaba, Tomohiro; Tokumoto, Yuta; Miyazaki, Yusuke; Inoue, Naoyuki; Maseda, Hideaki; Nakajima-Kambe, Toshiaki; Uchiyama, Hiroo

    2013-01-01

    Succinoyl trehalose lipids (STLs) are promising glycolipid biosurfactants produced from n-alkanes that are secreted by Rhodococcus species bacteria. These compounds not only exhibit unique interfacial properties but also demonstrate versatile biochemical actions. In this study, three novel types of genes involved in the biosynthesis of STLs, including a putative acyl coenzyme A (acyl-CoA) transferase (tlsA), fructose-bisphosphate aldolase (fda), and alkane monooxygenase (alkB), were identified. The predicted functions of these genes indicate that alkane metabolism, sugar synthesis, and the addition of acyl groups are important for the biosynthesis of STLs. Based on these results, we propose a biosynthesis pathway for STLs from alkanes in Rhodococcus sp. strain SD-74. By overexpressing tlsA, we achieved a 2-fold increase in the production of STLs. This study advances our understanding of bacterial glycolipid production in Rhodococcus species. PMID:24038682

  13. Toxic Effects of Tetrabromobisphenol A on Thyroid Hormones in SD Rats and the Derived-reference Dose.

    PubMed

    Yang, Yan; Ni, Wei Wei; Yu, Lin; Cai, Ze; Yu, Yun Jiang

    2016-04-01

    The present study determined the thyroid hormone interference of tetrabromobisphenol A (TBBPA) in Sprague-Dawley (SD) rats, and the derived-reference dose (RfD) of different endpoint effects on mammals based on experimental results and data collection. Based on repeated exposure toxicity tests on mammals and extensive research, the present study used BMDS240 Software to derive a benchmark dose, and analyzed the accuracy and uncertainty, and similarity with other studies. Test results on triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) demonstrated that all the indicators presented a non-monotonous dose-effect relationship clearly, except TSH in male rats exposed to 0-1000 mg/kg BW per day. Therefore, RfDs were derived from different critical effects. In summary, RfD for mammals in the present study was found to be 0.6 mg/kg per day. PMID:27241741

  14. 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.

  15. Deletion of the murine ATP/UTP receptor P2Y2 alters mechanical and thermal response properties in polymodal cutaneous afferents.

    PubMed

    Molliver, Derek C; Rau, Kristofer K; Jankowski, Michael P; Soneji, Deepak J; Baumbauer, Kyle M; Koerber, H Richard

    2016-09-22

    P2Y2 is a member of the P2Y family of G protein-coupled nucleotide receptors that is widely co-expressed with TRPV1 in peripheral sensory neurons of the dorsal root ganglia. To characterize P2Y2 function in cutaneous afferents, intracellular recordings from mouse sensory neurons were made using an ex vivo preparation in which hindlimb skin, saphenous nerve, dorsal root ganglia and spinal cord are dissected intact. The peripheral response properties of individual cutaneous C-fibers were analyzed using digitally controlled mechanical and thermal stimuli in male P2Y2(+/+) and P2Y2(-/-) mice. Selected sensory neurons were labeled with Neurobiotin and further characterized by immunohistochemistry. In wildtype preparations, C-fibers responding to both mechanical and thermal stimuli (CMH or CMHC) preferentially bound the lectin marker IB4 and were always immunonegative for TRPV1. Conversely, cells that fired robustly to noxious heat, but were insensitive to mechanical stimuli, were TRPV1-positive and IB4-negative. P2Y2 gene deletion resulted in reduced firing by TRPV1-negative CMH fibers to a range of heat stimuli. However, we also identified an atypical population of IB4-negative, TRPV1-positive CMH fibers. Compared to wildtype CMH fibers, these TRPV1-positive neurons exhibited lower firing rates in response to mechanical stimulation, but had increased firing to noxious heat (43-51°C). Collectively, these results demonstrate that P2Y2 contributes to response properties of cutaneous afferents, as P2Y2 deletion reduces responsiveness of conventional unmyelinated polymodal afferents to heat and appears to result in the acquisition of mechanical responsiveness in a subset of TRPV1-expressing afferents. PMID:27393251

  16. NLTE spectral analysis of the sdOB primary of the eclipsing binary system LB 3459 (AA Dor)

    NASA Astrophysics Data System (ADS)

    Rauch, T.

    2000-04-01

    We present a spectral analysis of the sdOB primary star of the binary system LB 3459 based on high-resolution high-S/N optical and UV spectra. The metal abundances are determined by means of state-of-the-art NLTE model atmospheres. We determined Teffw42 and log gw{5.2} within very small error limits. The He (1/125 solar), C (1/265), N (1/33), O (1/12), and Si (1/5) abundances appear strongly depleted while that of Fe and Ni are roughly solar and Mg is strongly enriched by a factor of 6. The spectroscopic distance to LB 3459 is d = 396 pc. The mass of the primary component of LB 3459 is 0.330 M_sun derived from comparisons with theoretical models for sdO stars in the log T_eff - \\log g plane. The mass of the secondary is then 0.066 M_sun derived from the mass function. There remains some disagreement between the radius derived from log g and the above mass, and that derived from analysis of the radial-velocity curve and the eclipse curves. LB 3459 is a close binary system which had experienced a common envelope (CE) phase during its evolution. It fits in the ``low mass case B'' scenario of Iben & Livio (1993) and the secondary is a brown dwarf. The spectroscopically determined rotational velocity of the primary is v_rot = 34 ± 10 km* sec-1. Thus even bound rotation (v_rot = 45.7 km* sec-1) cannot be ruled out. Based on observations collected at the European Southern Observatory, La Silla, Chile (proposals 55.D-0319, 56.C-0165) and on data retrieved from the International Ultraviolet Explorer (IUE) Final Archive.

  17. 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. PMID:26490924

  18. 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

  19. Switching of platelet P2Y12 receptor inhibitors in patients with acute coronary syndromes undergoing percutaneous coronary intervention: Review of the literature and practical considerations.

    PubMed

    De Luca, Leonardo; Capranzano, Piera; Patti, Giuseppe; Parodi, Guido

    2016-06-01

    The combination of aspirin and a P2Y12 receptor inhibitor is the cornerstone of treatment in patients with acute coronary syndromes (ACSs) and in those undergoing percutaneous coronary intervention (PCI). At the present time, 3 different oral P2Y12 receptor inhibitors are available on the market; 2 have obtained the indication for ACS (clopidogrel and ticagrelor) and 1 for ACS with planned PCI (prasugrel). An intravenous direct acting P2Y12 inhibitor, cangrelor, has also been recently approved by US and European regulatory agencies for patients undergoing PCI. Although the correct timing and modality of transition from intravenous cangrelor to oral P2Y12 inhibitors is still controversial and needs further evidence, switching between oral P2Y12 receptor inhibitors frequently occurs in clinical practice for several reasons. This practice raises the question of the relative safety of this strategy and of which switching approaches are preferable. In this article, we review the data on switching antiplatelet treatment strategies with P2Y12 receptor inhibitors and discuss practical considerations for switching therapies in patients with ACS undergoing PCI. PMID:27264219

  20. 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.

  1. 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.

  2. 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.

  3. High-resolution characterization of microstructural evolution in RbxFe2-ySe2 crystals on annealing

    NASA Astrophysics Data System (ADS)

    Speller, S. C.; Dudin, P.; Fitzgerald, S.; Hughes, G. M.; Kruska, K.; Britton, T. B.; Krzton-Maziopa, A.; Pomjakushina, E.; Conder, K.; Barinov, A.; Grovenor, C. R. M.

    2014-07-01

    The superconducting and magnetic properties of phase-separated AxFe2-ySe2 compounds are known to depend on postgrowth heat treatments and cooling profiles. This paper focuses on the evolution of microstructure on annealing and how this influences the superconducting properties of RbxFe2-ySe2 single crystals. We find that the minority phase in the as-grown crystal has increased unit cell anisotropy (c /a ratio), reduced Rb content, and increased Fe content compared to the main phase. The microstructure is rather complex, with two-phase mesoscopic plate-shaped features aligned along {113} habit planes. The minority phases are strongly faceted on the {113} planes, which we have shown to be driven by minimizing the volume strain energy introduced as a result of the phase transformation. Annealing at 488 K results in coarsening of the mesoscopic plate-shaped features and the formation of a third distinct phase. The subtle differences in structure and chemistry of the minority phase(s) in the crystals are thought to be responsible for changes in the superconducting transition temperature. In addition, scanning photoemission microscopy has clearly shown that the electronic structure of the minority phase has a higher occupied density of states of the low binding energy Fe3d orbitals, which is characteristic of crystals that exhibit superconductivity. This demonstrates a clear correlation between the Fe-vacancy-free phase with high c /a ratio and the electronic structure characteristics of the superconducting phase.

  4. 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

  5. Dirac Nodes and Quantized Thermal Hall Conductance in the Vortex State of d_x^2-y^2 Superconductors

    NASA Astrophysics Data System (ADS)

    Vishwanath, Ashvin

    2001-03-01

    We consider quasiparticles in a d_x^2-y^2 superconductor in the presence of a vortex lattice. Within the linearized approximation, we demonstrate that the Dirac nodes continue to exist at the chemical potential, as long as the vortex lattice is inversion symmetric. The approximate symmetry that protects these Dirac nodes is identified. On going beyond the linearized approximation (by retaining terms that break the particle-hole symmetry of the electron dispersion) the Dirac quasiparticles now acquire a mass term that induces a gap at the Fermi energy. As is well known in the theory of 2D Dirac equations, this leads to a quantized Hall conductance, which in this context implies a quantized spin Hall conductance and a quantized thermal Hall conductance (more precisely the ratio of thermal Hall conductance to temperature is quantized lim_Tarrow 0κ_xy/T = 2fracπ^2 k_B^23 h). Thus, the state is topologically equivalent to a d_x^2-y^2 + id_xy superconductor. In addition to this prediction, our analysis also provides information on the size of the gap (and thus the temperature scale below which quantization is expected) and its parametric dependence on various physical quantities. Experimentally, this quantization of thermal Hall conductance should be seen at sufficiently low temperatures if the induced gap exceeds the Zeeman splitting. Relevant experiments on YBa_2Cu_3O7 will be reviewed and compared against the theory.

  6. Salvianolic acid B inhibits platelets as a P2Y12 antagonist and PDE inhibitor: evidence from clinic to laboratory.

    PubMed

    Liu, Lei; Li, Jian; Zhang, Yan; Zhang, Shenghui; Ye, Jianqin; Wen, Zhichao; Ding, Jianping; Kunapuli, Satya P; Luo, Xinping; Ding, Zhongren

    2014-10-01

    Salviae miltiorrhiza (Danshen) has been used for thousands of years in China and some other Asian countries to treat atherothrombotic diseases. Salvianolate which consists of three water-soluble ingredients purified from Salviae miltiorrhiza, has been approved by Chinese SFDA to treat coronary artery disease. So far, there is no evidence clearly showing the clinical efficiency of salvianolate and the underlying mechanism. This study is to evaluate the effects of salvianolate on platelets in patients with acute coronary syndrome and explore the underlying mechanism. We evaluated the effects of salvianolate on platelets in patients with acute coronary syndrome by measuring ADP-induced PAC-1 binding and P-selectin expression on platelets. Salvianolate significantly potentiated the antiplatelet effects of standard dual antiplatelet therapy. We also investigated the antiplatelet effects of salvianolatic acid B (Sal-B), the major component which composes 85% of salvianolate. Sal-B inhibits human platelet activation induced by multiple agonists in vitro by inhibiting phosphodiesterase (PDE) and antagonizing P2Y12 receptor. For the first time, we show the antiplatelet efficiency of salvianolate in ACS patients undergoing treatment with clopidogrel plus aspirin, and demonstrate that Sal-B, the major component of salvianolate inhibits human platelet activation via PDE inhibition and P2Y12 antagonism which may account for the clinical antiplatelet effects of salvianolate. Our results suggest that Sal-B may substitute salvianolate for clinical use. PMID:25077998

  7. Dyspnea related to reversibly-binding P2Y12 inhibitors: A review of the pathophysiology, clinical presentation and diagnostics.

    PubMed

    Unverdorben, Martin; Parodi, Guido; Pistolesi, Massimo; Storey, Robert F

    2016-01-01

    Dyspnea is a common symptom physiologically associated with strenuous exercise and pathologically reflecting well-known diseases and conditions that are predominantly pulmonary, cardiovascular, and weight-related in origin. Dyspnea improves with appropriate measures that enhance physical performance and treatment of the underlying diseases. Dyspnea is less commonly triggered by other causes such as the environment (e.g., ozone), drugs, and others, some of which do not seem to affect bronchopulmonary function as evidenced by normal results of comprehensive pulmonary function testing. In cardiovascular medicine, dyspnea has recently attracted attention because it has been reported that this symptom occurs more frequently with the administration of the new oral reversibly-binding platelet P2Y12 receptor inhibitors ticagrelor [1-6], cangrelor [7-10], and elinogrel [11]. This paper succinctly addresses the current understanding of the pathophysiology, clinical presentation, and diagnostics of dyspnea, associated either with bronchopulmonary function impairment, as triggered mainly by pulmonary and cardiovascular diseases, or without bronchopulmonary function impairment, as induced by endogenous or external compounds such as drugs in order to provide a context for understanding, recognizing and managing P2Y12 inhibitor-induced dyspnea. PMID:26386945

  8. P2Y receptor-mediated transient relaxation of rat longitudinal ileum preparations involves phospholipase C activation, intracellular Ca2+ release and SK channel activation

    PubMed Central

    Mader, Felix; Krause, Ludwig; Tokay, Tursonjan; Hakenberg, Oliver W; Köhling, Rüdiger; Kirschstein, Timo

    2016-01-01

    Aim: Purinergic signaling plays a major role in the enteric nervous system, where it governs gut motility through a number of P2X and P2Y receptors. The aim of this study was to investigate the P2Y receptor-mediated motility in rat longitudinal ileum preparations. Methods: Ileum smooth muscle strips were prepared from rats, and fixed in an organ bath. Isometric contraction and relaxation responses of the muscle strips were measured with force transducers. Drugs were applied by adding of stock solutions to the organ bath to yield the individual final concentrations. Results: Application of the non-hydrolyzable P2 receptor agonists α,β-Me-ATP or 2-Me-S-ADP (10, 100 μmol/L) dose-dependently elicited a transient relaxation response followed by a sustained contraction. The relaxation response was largely blocked by SK channel blockers apamin (500 nmol/L) and UCL1684 (10 μmol/L), PLC inhibitor U73122 (100 μmol/L), IP3 receptor blocker 2-APB (100 μmol/L) or sarcoendoplasmic Ca2+ ATPase inhibitor thapsigargin (1 μmol/L), but not affected by atropine, NO synthase blocker L-NAME or tetrodotoxin. Furthermore, α,β-Me-ATP-induced relaxation was suppressed by P2Y1 receptor antagonist MRS2179 (50 μmol/L) or P2Y13 receptor antagonist MRS2211 (100 μmol/L), and was abolished by co-application of the two antagonists, whereas 2-Me-S-ADP-induced relaxation was abolished by P2Y6 receptor antagonist MRS2578 (50 μmol/L). In addition, P2Y1 receptor antagonist MRS2500 (1 μmol/L) not only abolished α,β-Me-ATP-induced relaxation, but also suppressed 2-Me-S-ADP-induced relaxation. Conclusion: P2Y receptor agonist-induced transient relaxation of rat ileum smooth muscle strips is mediated predominantly by P2Y1 receptor, but also by P2Y6 and P2Y13 receptors, and involves PLC, IP3, Ca2+ release and SK channel activation, but is independent of acetylcholine and NO release. PMID:27018177

  9. Activation of P2X(7) receptors stimulates the expression of P2Y(2) receptor mRNA in astrocytes cultured from rat brain.

    PubMed

    D'Alimonte, I; Ciccarelli, R; Di Iorio, P; Nargi, E; Buccella, S; Giuliani, P; Rathbone, M P; Jiang, S; Caciagli, F; Ballerini, P

    2007-01-01

    Under pathological conditions brain cells release ATP at concentrations reported to activate P2X(7) ionotropic receptor subtypes expressed in both neuronal and glial cells. In the present study we report that the most potent P2X(7) receptor agonist BzATP stimulates the expression of the metabotropic ATP receptor P2Y(2) in cultured rat brain astrocytes. In other cell types several kinds of stimulation, including stress or injury, induce P2Y(2) expression that, in turn, is involved in different cell reactions. Similarly, it has recently been found that in astrocytes and astrocytoma cells P2Y(2) sites can trigger neuroprotective pathways through the activation of several mechanisms, including the induction of genes for antiapoptotic factors, neurotrophins, growth factors and neuropeptides. Here we present evidence that P2Y(2) mRNA expression in cultured astrocytes peaks 6 h after BzATP exposure and returns to basal levels after 24 h. This effect was mimicked by high ATP concentrations (1 mM) and was abolished by P2X(7)-antagonists oATP and BBG. The BzATP-evoked P2Y(2) receptor up-regulation in cultured astrocytes was coupled to an increased UTP-mediated intracellular calcium response. This effect was inhibited by oATP and BBG and by P2Y(2)siRNA, thus supporting evidence of increased P2Y(2) activity. To further investigate the mechanisms by which P2X(7) receptors mediated the P2Y(2) mRNA up-regulation, the cells were pre-treated with the chelating agent EGTA, or with inhibitors of mitogen-activated kinase (MAPK) (PD98059) or protein kinase C, (GF109203X). Each inhibitor significantly reduced the extent to which BzATP induced P2Y(2) mRNA. Both BzATP and ATP (1 mM) increased ERK1/2 activation. P2X(7)-induced ERK1/2 phosphorylation was unaffected by pre-treatment of astrocytes with EGTA whereas it was inhibited by GF109203X. Phorbol-12-myristate-13-acetate (PMA), an activator of PKCs, rapidly increased ERK1/2 activation. We conclude that activation of P2X(7) receptors in

  10. SD-208, a Novel Protein Kinase D Inhibitor, Blocks Prostate Cancer Cell Proliferation and Tumor Growth In Vivo by Inducing G2/M Cell Cycle Arrest

    PubMed Central

    Tandon, Manuj; Salamoun, Joseph M.; Carder, Evan J.; Farber, Elisa; Xu, Shuping; Deng, Fan; Tang, Hua; Wipf, Peter; Wang, Q. Jane

    2015-01-01

    Protein kinase D (PKD) has been implicated in many aspects of tumorigenesis and progression, and is an emerging molecular target for the development of anticancer therapy. Despite recent advancement in the development of potent and selective PKD small molecule inhibitors, the availability of in vivo active PKD inhibitors remains sparse. In this study, we describe the discovery of a novel PKD small molecule inhibitor, SD-208, from a targeted kinase inhibitor library screen, and the synthesis of a series of analogs to probe the structure-activity relationship (SAR) vs. PKD1. SD-208 displayed a narrow SAR profile, was an ATP-competitive pan-PKD inhibitor with low nanomolar potency and was cell active. Targeted inhibition of PKD by SD-208 resulted in potent inhibition of cell proliferation, an effect that could be reversed by overexpressed PKD1 or PKD3. SD-208 also blocked prostate cancer cell survival and invasion, and arrested cells in the G2/M phase of the cell cycle. Mechanistically, SD-208-induced G2/M arrest was accompanied by an increase in levels of p21 in DU145 and PC3 cells as well as elevated phosphorylation of Cdc2 and Cdc25C in DU145 cells. Most importantly, SD-208 given orally for 24 days significantly abrogated the growth of PC3 subcutaneous tumor xenografts in nude mice, which was accompanied by reduced proliferation and increased apoptosis and decreased expression of PKD biomarkers including survivin and Bcl-xL. Our study has identified SD-208 as a novel efficacious PKD small molecule inhibitor, demonstrating the therapeutic potential of targeted inhibition of PKD for prostate cancer treatment. PMID:25747583

  11. 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.

  12. Oliver E. Buckley Condensed Matter Prize Lecture: S-d Exchange, Spin Accumulation, And The Roots Of Spintronics

    NASA Astrophysics Data System (ADS)

    Berger, Luc

    2013-03-01

    The success of spintronics in metals such as nickel, cobalt, Ni-Fe and Ni-Co is based on the existence of high-mobility spin-up 4s electrons at the Fermi level, which carry most of the current. The spin-up Fermi level is located above the top of the 3d band. This basic fact, first recognized by Mott in 1936, was confirmed by the Hall-effect measurements of Pugh et al. (1950-1965), and by data of deviation from Matthiessen's rule by Campbell, Fert and Jaoul (1967-1977). In order to explain giant magnetoresistance and the existence of the spin-transfer torque, an interaction is needed which couples 4s conduction electrons to magnetic 3d electrons. This is the s-d exchange interaction, introduced by Vonsovskii in 1946 and Zener in 1951. Theories of Gilbert damping, based on s-d exchange, were soon developed (Turov (1955), Mitchell (1957)). But a serious problem was caused by the existence of a momentum gap between spin-up and spin-down Fermi surfaces, which prevents spin switching from happening at low T. The problem can be solved if local defects exist which act as extra sources of momentum. One such source is spin-flip scattering (Turov (1961), Heinrich, Freitova and Kambersky (1967)). A second one is the presence of an interface (Slonczewski (1996), Berger (1996)). Spin accumulation is another concept of importance to spintronics. It represents an imbalance between spin-up and spin-down Fermi levels. Introduced by Aronov in 1976, it was developed by Johnson and Silsbee (1985-1993) and by Valet and Fert (1993). It is the hidden agent through which the current ``pumps'' energy into many spintronics devices. In semiconductor lasers, the same role is played by the difference between conduction-band and valence-band Fermi levels. A momentum gap problem also exists in lasers made of indirect-gap semiconductors, and it is solved similarly.

  13. Trends in P2Y12 Inhibitor Use in Patients Referred for Invasive Evaluation of Coronary Artery Disease in Contemporary US Practice.

    PubMed

    Fan, Weihong; Plent, Stephanie; Prats, Jayne; Deliargyris, Efthymios N

    2016-05-01

    Practice in patients undergoing invasive evaluation for coronary artery disease is variable regarding choice of P2Y12 inhibitor and timing of treatment initiation and is usually dictated by institutional or even individual operator preference. Limited data are available on the actual patterns of P2Y12 inhibitor use in contemporary practice in the United States. We used electronic medical records from the Cerner "Health Facts" database of adults who underwent coronary angiography with or without percutaneous coronary intervention (PCI) from January 2008 to June 2013 and who received a loading dose of clopidogrel, prasugrel, or ticagrelor at any time from 48 hours before the start of procedure up to 6 hours after. Timing of P2Y12 inhibitor administration was categorized as >2 hours before, 0 to 2 hours before (pretreatment groups), or after the start of procedure. Results were also evaluated according to type of P2Y12 inhibitor and patient clinical presentation. A total of 37,964 patients underwent coronary angiography, and 28,306 proceeded to PCI. Pretreatment with a P2Y12 inhibitor was observed in 28% and 23% in the overall and PCI populations, respectively. Moderate variability of pretreatment rates was noted relative to clinical presentation and P2Y12 inhibitor type. Pretreatment rates remained fairly constant over time with the exception of a decreasing trend with prasugrel. In conclusion, among patients referred for invasive evaluation of coronary artery disease, P2Y12 inhibitor pretreatment was low in contemporary US practice, an observation consistent over time and for all available agents and clinical presentations. PMID:27001447

  14. 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. PMID:25855780

  15. The P2Y2 Receptor Interacts with VE-Cadherin and VEGF Receptor-2 to Regulate Rac1 Activity in Endothelial Cells

    PubMed Central

    Liao, Zhongji; Cao, Chen; Wang, Jianjie; Huxley, Virginia H.; Baker, Olga; Weisman, Gary A.

    2015-01-01

    Vascular endothelial cadherin (VE-cadherin) mediates homophylic adhesion between endothelial cells and is an important regulator of angiogenesis, blood vessel permeability and leukocyte trafficking. Rac1, a member of the Rho family of GTPases, controls VE-cadherin adhesion by acting downstream of several growth factors, including angiopoietin-1 and vascular endothelial growth factor (VEGF). Here we show that UTP-induced activation of the Gq protein-coupled P2Y2 nucleotide receptor (P2Y2R) in human coronary artery endothelial cells (HCAECs) activated Rac1 and caused a transient complex to form between P2Y2R, VE-cadherin and VEGF receptor-2 (VEGFR-2). Knockdown of VE-cadherin expression with siRNA did not affect UTP-induced activation of extracellular signal-regulated kinases 1/2 (ERK1/2) but led to a loss of UTP-induced Rac1 activation and tyrosine phosphorylation of p120 catenin, a cytoplasmic protein known to interact with VE-cadherin. Activation of the P2Y2R by UTP also caused a prolonged interaction between p120 catenin and vav2 (a guanine nucleotide exchange factor for Rac) that correlated with the kinetics of UTP-induced tyrosine phosphorylation of p120 catenin and VE-cadherin. Inhibitors of VEGFR-2 (SU1498) or Src (PP2) significantly diminished UTP-induced Rac1 activation, tyrosine phosphorylation of p120 catenin and VE-cadherin, and association of the P2Y2R with VE-cadherin and p120 catenin with vav2. These findings suggest that the P2Y2R uses Src and VEGFR-2 to mediate association of the P2Y2R with VE-cadherin complexes in endothelial adherens junctions to activate Rac1. PMID:25657827

  16. Paleointensity estimates derived from non-SD recording materials: Testing the IZZI technique on MD slag and a new bootstrap procedure

    NASA Astrophysics Data System (ADS)

    Shaar, R.; Ron, H.; Tauxe, L.; Kessel, R.; Agnon, A.

    2011-12-01

    Experimental techniques to determine paleomagnetic field intensity are based on a theoretical framework that is valid only for single-domain (SD) ferromagnetic particles. Yet, most of the available materials exhibit distinctly non-SD properties. Hence, designing a robust paleointensity methodology for non-SD is a fundamental challenge in paleomagnetism. Here we test the IZZI Thellier absolute paleointensity technique on slag material that has properties of small MD. The test has two purposes: 1) to describe the characteristic non-SD patterns occurring in Arai plots, and 2) to identify the optimal approach in interpreting non-SD behavior. We produced 4 synthetic re-melted slag samples with identical magneto-mineralogical properties under field intensities of 20, 40, 60 and 80 μT. We ran three batches of IZZI paleointensity experiments on 10 specimens per samples. The IZZI experiments were designed to identify the dependency of the results on the ratio and the angle between the field used in the paleointensity experiment (BTRM) and the field in which the NRM was acquired (BNRM). The results demonstrate different types of Arai plots, systematically dependent on the angle and the proportion between BTRM and BNRM. Straight-line Arai plots occur when the two fields are parallel and equal, and seem to always give the 'true' slope. Convex curves occur when BTRM is parallel and significantly stronger than BNRM. Concave curves occur in all the other cases and yield two end-case slopes that are always different from the 'true' slope. The zigzags of the Arai plot increase with the proportion between BTRM and BNRM, and as the angle between BTRM and BNRM approaches 90°. We test the accuracy of the commonly used data analysis approach of best fitting line through a chosen segment of the Arai plot. We conclude that best fitting line in curved plots cannot provide robust paleointensity estimates. However, the two 'end-case' slopes in concave curves can provide adequate

  17. Central role for hydrogen peroxide in P2Y1 ADP receptor-mediated cellular responses in vascular endothelium

    PubMed Central

    Kalwa, Hermann; Sartoretto, Juliano L.; Martinelli, Roberta; Romero, Natalia; Steinhorn, Benjamin S.; Tao, Ming; Ozaki, C. Keith; Carman, Christopher V.; Michel, Thomas

    2014-01-01

    ADP activates a family of cell surface receptors that modulate signaling pathways in a broad range of cells. ADP receptor antagonists are widely used to treat cardiovascular disease states. These studies identify a critical role for the stable reactive oxygen species hydrogen peroxide (H2O2) in mediating cellular responses activated by the G protein-coupled P2Y1 receptor for ADP. We found that ADP-dependent phosphorylation of key endothelial signaling proteins—including endothelial nitric oxide synthase, AMP-activated protein kinase, and the actin-binding MARCKS protein—was blocked by preincubation with PEG-catalase, which degrades H2O2. ADP treatment promoted the H2O2-dependent phosphorylation of c-Abl, a nonreceptor tyrosine kinase that modulates the actin cytoskeleton. Cellular imaging experiments using fluorescence resonance energy transfer-based biosensors revealed that ADP-stimulated activation of the cytoskeleton-associated small GTPase Rac1 was independent of H2O2. However, Rac1-dependent activation of AMP-activated protein kinase, the signaling phospholipid phosphatidylinositol-(4, 5)-bisphosphate, and the c-Abl–interacting protein CrkII are mediated by H2O2. We transfected endothelial cells with differentially targeted HyPer2 H2O2 biosensors and found that ADP promoted a marked increase in H2O2 levels in the cytosol and caveolae, and a smaller increase in mitochondria. We performed a screen for P2Y1 receptor-mediated receptor tyrosine kinase transactivation and discovered that ADP transactivates Fms-like tyrosine kinase 3 (Flt3), a receptor tyrosine kinase expressed in these cells. Our observation that P2Y1 receptor-mediated responses involve Flt3 transactivation may identify a unique mechanism whereby cancer chemotherapy with receptor tyrosine kinase inhibitors promotes vascular dysfunction. Taken together, these findings establish a critical role for endogenous H2O2 in control of ADP-mediated signaling responses in the vascular wall. PMID:24550450

  18. Comparison of P2Y12 receptor inhibition by clopidogrel and prasugrel in patients undergoing percutaneous coronary intervention.

    PubMed

    Haq, M M; Ahsan, C H; Amin, M N; Karim, M R; Ali, M L; Khan, S R; Chowdhury, M Z; Mansur, M; Millat, M H; Rashid, M A

    2013-12-01

    Dual antiplatelet treatment (DAPT) with aspirin and clopidogrel is vital after percutaneous coronary intervention (PCI). Clopidogrel and prasugrel act on P2Y12 platelet surface receptors. Both these P2Y12 inhibitors are pro-drugs and depend on cytochrome system of the liver for their conversion to active metabolite. There is growing concern regarding suboptimal response in platelet inhibition by clopidogrel. Verify Now system got approval by Federal Drug Administration, USA, for assessing platelet function as its result is almost comparable to gold standard Light Transmission Aggregometry (LTA). There are no data on the prevalence of clopidogrel resistance in Bangladeshi population. Prasugrel, as an antiplatelet drug, is a newer introduction in this country. This study will show light on the efficacy of these drugs on our population especially in patients who undergo PCI where DAPT is mandatory. A total 120 (60 diabetics) patients with Acute Coronary Syndrome (ACS), were alternatively given 600 mg clopidogrel loading dose (LD) followed by 75 mg maintenance dose (MD) daily or 60 mg LD of prasugrel followed by 10 mg MD daily. Five samples of blood were taken at different time intervals over a period of 2 weeks. Measurement of percent inhibition of P2Y12 was done by VerifyNow. Patients who showed less than 20% inhibition (clopidogrel resistant) at any stage were switched to prasugrel. The outcomes of clopidogrel, prasugrel and clopidogrel switched to prasugrel groups were then compared. Nearly half (46.7%) of the patients in the clopidogrel group was found resistant to the drug as opposed to none in the prasugrel group. No difference was found between diabetic and non-diabetic subjects with respect to drug resistance. Intracoronary blood samples showed high degree of platelet inhibition with prasugrel. There was a gradual decline of platelet inhibition over two weeks with prasugrel. Almost fifty percent of the population is clopidogrel resistant in our study

  19. 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.

  20. An Asteroseismological Analysis of the Short-Period Pulsating sdB Star EC 05217-3914

    NASA Astrophysics Data System (ADS)

    Billères, M.; Fontaine, G.

    2005-07-01

    We present the results of a detailed asteroseimological analysis of the southern hemisphere sdB pulsator EC 05217-3914. This analysis rests on our gathering of high S/N ratio observations at the NTT using the SUSI2 camera. Some 37 h of data were obtained over a 5 night run. We uncovered several frequency components in the period range 129-218 s, several of which form multiplets with equally spaced components. The latter are best explained in terms of rotational splitting in a star with a rotation period of 13.1 h. Excluding the rotationally-split components, we identified 5 independent pulsation modes with which to play the game of asteroseismology. Using an efficient period-matching code we explored the parameter space and found an excellent fit to the observed periods. We present the results of this exercise: our preliminary identification of the pulsation modes in EC 05217-3914 and the determination of its fundamental parameters through asteroseismology.

  1. A planet orbiting an sdB star and an M dwarf in 2M 1938+4603

    NASA Astrophysics Data System (ADS)

    Blokesz, Adam; Baran, Andrzej; Zola, Stanislaw

    2015-09-01

    We present a preliminary analysis of the 2M 1938+4603 star. It is an eclipsing binary system consisting of a primary sdB component and a secondary M dwarf. The photometric data are dominated by mutual eclipses and a very strong reflection effect. The primary has a fairly rich pulsation spectrum which can be used to study its interior. On the other hand, the pulsations affect the binary trend and vice versa what makes the analysis very difficult. Therefore, we attempted at proper modeling of the light variation due to eclipses and reflection and their removal from the data so it does not affect the Fourier analysis of stellar pulsations. We focus on mid-times of over 16 000 primary and secondary minima, which were used to verify stability of the orbital period. The O-C diagram indicates possible parabolic and sinusoidal variations, commonly explained by period changes caused by evolution and a presence of a third body, respectively.

  2. Improving the Significance of MM/SD Risk Analysis by Application of the SRL Ballistic Limit Equation

    NASA Astrophysics Data System (ADS)

    Schafer, Frank; Putzar, Robin; Ryan, Shannon; Lambert, Michel

    2009-03-01

    In this paper, a new ballistic limit equation (BLE) for satellite equipment placed behind satellite structure walls is presented. Application of this equation in micrometeoroid and space debris (MM/SD) risk analysis (RA) tools for satellites can lead to a more realistic quantitative assessment of the actual failure risk of satellite equipment from hypervelocity impacts (HVI) and hence, of the failure risk of a satellite. This is because in contrast to the BLEs that are currently in use in RA tools, in the new equation the intrinsic shielding capabilities of the satellite equipment are considered explicitly.The BLE has been developed for application to configurations consisting of a Whipple shield or a honeycomb sandwich panel placed in front of a backwall. It considers explicitly the thickness, material and spacing of each of the three involved plates. The backwall represents the cover plate or the external wall of spacecraft equipment that is placed behind the spacecraft's structure wall. The BLE has been experimentally calibrated to the most common spacecraft equipment: fuel and heat pipes, pressure vessels, electronics boxes, harness, and batteries. Further, suitable failure criteria have been defined for each equipment type. The critical projectile masses calculated with the new BLE for satellite equipment placed behind satellite structure walls are considerably larger than the critical projectile masses calculated for the standalone structure wall of the satellite.

  3. Successful prevention of post-transfusion Rh alloimmunization by intravenous Rho (D) immune globulin (WinRho SD).

    PubMed

    Anderson, B; Shad, A T; Gootenberg, J E; Sandler, S G

    1999-03-01

    Alloimmunization to the D blood group antigen following the transfusion of D-positive red blood cells to a D-negative recipient may be prevented in most persons by a prompt and adequate dose of Rho (D) immune globulin (RhIG). Until recently, the only RhIG approved by the US Food and Drug Administration (FDA) for this indication required intramuscular injection, an inconvenient and painful route for the relatively large volume that may be required. We describe the successful prevention of Rh alloimmunization following the unintentional transfusion of D-positive red blood cells to a D-negative infant by the intravenous infusion of WinRho SD, a new RhIG that is FDA-approved for prevention of post-transfusion Rh alloimmunization by intravenous administration. We believe that this more convenient and less painful approach should be the treatment of choice for preventing Rh alloimmunization following the transfusion of D-positive red cells to a D-negative recipient. PMID:10072121

  4. 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.

  5. Mode identification based on time-series spectrophotometry for the bright rapid sdB pulsator EC 01541-1409

    NASA Astrophysics Data System (ADS)

    Randall, S. K.; Fontaine, G.; Geier, S.; Van Grootel, V.; Brassard, P.

    2014-03-01

    We present an analysis of time-resolved spectrophotometry gathered with FORS/VLT for the rapidly pulsating hot B subdwarf EC 01541-1409 with the aim of identifying the degree index ℓ of the larger amplitude modes. This mode identification can be extremely useful in detailed searches for viable asteroseismic models in parameter space, and can be crucial for testing the validity of a solution a posteriori. To achieve it, we exploit the ℓ-dependence of the monochromatic amplitude, phase, and velocity-to-amplitude ratio of a mode as a function of wavelength. We use the ℓ-sensitive phase lag between the flux perturbation and the radial velocity as an additional diagnostic tool. On this basis, we are able to unambiguously identify the dominant 140.5 s pulsation of our target as a radial mode, and the second-highest amplitude periodicity at 145.8 s as an ℓ = 2 mode. We further exploit the exceptionally high-sensitivity data that we gathered for the dominant mode to infer modal properties that are usually quite difficult to estimate in sdB pulsators, namely the physical values of the dimensionless radius, temperature, and surface gravity perturbations. Based on observations collected at the European Organisation for Astronomical Research in the Southern Hemisphere, Chile (proposal ID 087.D-0047).Appendix A is available in electronic form at http://www.aanda.org

  6. Sustained phase separation and spin glass in Co-doped KxFe2-ySe2 single crystals

    DOE PAGESBeta

    Ryu, Hyejin; Wang, Kefeng; Opacic, M.; Lazarevic, N.; Warren, J. B.; Popovic, Z. V.; Bozin, Emil S.; Petrovic, C.

    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

  7. Selective permeabilization of cervical cancer cells to an ionic DNA-binding cytotoxin by activation of P2Y receptors

    PubMed Central

    Bukhari, Maurish; Deng, Han; Jones, Noelle; Towne, Zachary; Woodworth, Craig D.; Samways, Damien S.K.

    2015-01-01

    Extracellular ATP is known to permeabilize certain cell types to polyatomic cations like YO-PRO1. Here, we report that extracellularly applied ATP stimulated rapid uptake and accumulation of an otherwise weakly membrane permeable fluorescent DNA-binding cytotoxin, Hoechst 33258, into cervical cancer cells. While ATP stimulated Hoechst 332uptake in 20–70% of cells from seven cervical cancer cell lines, it consistently stimulated uptake in less than 8% of cervical epithelial cells obtained from the normal transformation zone and ectocervix tissue of 10 patients. ATP-evoked Hoechst 33258 uptake was independent of ionotropic P2X receptors, but dependent on activation of P2Y receptors. Thus, we show here that cervical cancer cells can be selectively induced to take up and accumulate an ionic cytotoxin by exposure to extracellular ATP. PMID:25937122

  8. 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. PMID:27532447

  9. 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.

  10. The hybrid lattice of K(x)Fe(2-y)Se2: where superconductivity and magnetism coexist.

    PubMed

    Louca, Despina; Park, Keeseong; Li, Bing; Neuefeind, Joerg; Yan, Jiaqiang

    2013-01-01

    Much remains unknown of the microscopic origin of superconductivity in atomically disordered systems of amorphous alloys or in crystals riddled with defects. A manifestation of this conundrum is envisaged in the highly defective superconductor of K(x)Fe(2-y)Se2. How can superconductivity survive under such crude conditions that call for strong electron localization? Here, we show that the Fe sublattice is locally distorted and accommodates two kinds of Fe valence environments giving rise to a bimodal bond-distribution, with short and long Fe bonds. The bimodal bonds are present even as the system becomes superconducting in the presence of antiferromagnetism, with the weight continuously shifting from the short to the long with increasing K content. Such a hybrid state is most likely found in cuprates as well while our results point to the importance of the local atomic symmetry by which exchange interactions between local moments materialize. PMID:23782976

  11. A comparative analysis of the activity of ligands acting at P2X and P2Y receptor subtypes in models of neuropathic, acute and inflammatory pain

    PubMed Central

    Andó, RD; Méhész, B; Gyires, K; Illes, P; Sperlágh, B

    2010-01-01

    Background and purpose: This study was undertaken to compare the analgesic activity of antagonists acting at P2X1, P2X7, and P2Y12 receptors and agonists acting at P2Y1, P2Y2, P2Y4, and P2Y6 receptors in neuropathic, acute, and inflammatory pain. Experimental approach: The effect of the wide spectrum P2 receptor antagonist PPADS, the selective P2X7 receptor antagonist Brilliant Blue G (BBG), the P2X1 receptor antagonist (4,4′,4″,4-[carbonylbis(imino-5,1,3-benzenetriyl-bis(carbonylimino))]tetrakis-1,3-benzenedisulfonic acid, octasodium salt (NF449) and (8,8′-[carbonylbis(imino-3,1-phenylenecarbonylimino)]bis-1,3,5-naphthalene-trisulphonic acid, hexasodium salt (NF023), the P2Y12 receptor antagonist (2,2-dimethyl-propionic acid 3-(2-chloro-6-methylaminopurin-9-yl)-2-(2,2-dimethyl-propionyloxymethyl)-propylester (MRS2395), the selective P2Y1 receptor agonist ([[(1R,2R,3S,4R,5S)-4-[6-amino-2-(methylthio)-9H-purin-9-yl]-2,3-dihydroxybicyclo[3.1.0]hex-1-yl]methyl] diphosphoric acid mono ester trisodium salt (MRS2365), the P2Y2/P2Y4 agonist uridine-5′-triphosphate (UTP), and the P2Y4/P2Y6 agonist uridine-5′-diphosphate (UDP) were examined on mechanical allodynia in the Seltzer model of neuropathic pain, on acute thermal nociception, and on the inflammatory pain and oedema induced by complete Freund's adjuvant (CFA). Key results: MRS2365, MRS2395 and UTP, but not the other compounds, significantly alleviated mechanical allodynia in the neuropathic pain model, with the following rank order of minimal effective dose (mED) values: MRS2365 > MRS2395 > UTP. All compounds had a dose-dependent analgesic action in acute pain except BBG, which elicited hyperalgesia at a single dose. The rank order of mED values in acute pain was the following: MRS2365 > MRS2395 > NF449 > NF023 > UDP = UTP > PPADS. MRS2365 and MRS2395 had a profound, while BBG had a mild effect on inflammatory pain, with a following rank order of mED values: MRS2395 > MRS2365 > BBG. None of the tested

  12. Antagonism of P2Y1-induced vasorelaxation by acyl CoA: a critical role for palmitate and 3′-phosphate

    PubMed Central

    Alefishat, E; Alexander, SPH; Ralevic, V

    2013-01-01

    Background and Purpose Acyl derivatives of CoA have been shown to act as antagonists at human platelet and recombinant P2Y1 receptors, but little is known about their effects in the cardiovascular system. This study evaluated the effect of these endogenous nucleotide derivatives at P2Y1 receptors natively expressed in rat and porcine blood vessels. Experimental Approach Isometric tension recordings were used to evaluate the effects of CoA, acetyl CoA, palmitoyl CoA (PaCoA) and 3′-dephospho-palmitoyl-CoA on concentration relaxation–response curves to ADP and uridine triphosphate (UTP). A FlexStation monitored ADP- and UTP-evoked calcium responses in HEK293 cells. Key Results Acetyl CoA and PaCoA, but not CoA, inhibited endothelium-dependent relaxations to ADP with apparent selectivity for P2Y1 receptors (over P2Y2/4 receptors) in rat thoracic aorta; PaCoA was more potent than acetyl CoA (331-fold vs. fivefold shift of ADP response curve evoked by 10 μM PaCoA and acetyl CoA, respectively); the apparent pA2 value for PaCoA was 6.44. 3′-dephospho-palmitoyl-CoA (10 μM) was significantly less potent than PaCoA (20-fold shift). In porcine mesenteric arteries, PaCoA and the P2Y1 receptor antagonist MRS2500 blocked ADP-mediated endothelium-dependent relaxations; in contrast, they were ineffective against ADP-mediated endothelium-independent relaxation in porcine coronary arteries (which does not involve P2Y1 receptors). Calcium responses evoked by ADP activation of endogenous P2Y1 receptors in HEK293 cells were inhibited in the presence of PaCoA, which failed to alter responses to UTP (acting at endogenous P2Y2/4 receptors). Conclusions and Implications Acyl derivatives of CoA can act as endogenous selective antagonists of P2Y1 receptors in blood vessels, and this inhibitory effect critically depends on the palmitate and 3′-ribose phosphate substituents on CoA. PMID:23215951

  13. 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. PMID:27297894

  14. The fate of P2Y-related orphan receptors: GPR80/99 and GPR91 are receptors of dicarboxylic acids.

    PubMed

    Gonzalez, Nathalie Suarez; Communi, Didier; Hannedouche, Sébastien; Boeynaems, Jean-Marie

    2004-12-01

    Several orphan G protein-coupled receptors are structurally close to the family of P2Y nucleotide receptors: GPR80/99 and GPR91 are close to P2Y(1/2/4/6/11) receptors, whereas GPR87, H963 and GPR34 are close to P2Y(12/13/14). Over the years, several laboratories have attempted without success to identify the ligands of those receptors. In early 2004, two papers have been published: One claiming that GPR80/99 is an AMP receptor, called P2Y(15), and the other one showing that GPR80/99 is a receptor for alpha-ketoglutarate, while GPR91 is a succinate receptor. The accompanying paper by Qi et al. entirely supports that GPR80/99 is an alpha-ketoglutarate receptor and not an AMP receptor. The closeness of dicarboxylic acid and P2Y nucleotide receptors might be linked to the negative charges of both types of ligands and the involvement of conserved Arg residues in their neutralization. PMID:18404396

  15. A novel polyaspartate precursor method for the synthesis of LiCayMn2-yO4 nanoparticles for Li-ion batteries

    NASA Astrophysics Data System (ADS)

    Subramania, A.; Angayarkanni, N.; Niruba, N.; Vasudevan, T.

    2007-02-01

    Cubic spinel LiCayMn2-yO4 nanoparticles were synthesized using nitrates of Li+, Ca2+ and acetate of Mn2+ with aspartic acid as a polymerizable combustion fuel. They were dissolved in distilled water and then concentrated by heating to form a viscous resin which was transformed into a foam-like mass by drying at 120 °C. Phase pure LiCayMn2-yO4 powders were obtained by combustion of these foams. The decomposition temperature of the polyaspartate precursor was investigated by TG/DTA analysis. The structural property of the synthesized LiCayMn2-yO4 powders was confirmed by x-ray diffraction studies. The average particle size of the synthesized powders was calculated from the x-ray data using the Scherrer equation. TEM analysis was also carried out to confirm the particle size and surface morphology of the synthesized LiCayMn2-yO4 powder. Finally, electrochemical charge-discharge studies were carried out by assembling 2016 type electrochemical button cells using carbon as the anode and the synthesized LiCayMn2-yO4 as the cathode with microporous polymer electrolyte.

  16. Increased expression of NTPDases 2 and 3 in mesenteric endothelial cells during schistosomiasis favors leukocyte adhesion through P2Y1 receptors.

    PubMed

    Oliveira, Suellen Darc Santos; Oliveira, Nathália F; Meyer-Fernandes, José R; Savio, Luiz Eduardo Baggio; Ornelas, Flavia G I; Ferreira, Zulma S; Coutinho-Silva, Robson; Silva, Claudia Lucia Martins

    2016-07-01

    Schistosomiasis is caused by an intravascular parasite and linked to phenotypic changes in endothelial cells that favor inflammation. Endothelial cells express P2Y1 receptors (P2Y1R), and their activation by ADP favors leukocyte adhesion to the endothelial monolayer. We aimed to evaluate the influence of schistosomiasis upon endothelial purinergic signaling-mediated leukocyte adhesion. Mesenteric endothelial cells and mononuclear cells from control and Schistosoma mansoni-infected mice were used in co-culture. P2Y1R levels were similar in both groups. Basal leukocyte adhesion was higher in the infected than in the control group; leukocyte adhesion increased after treatment with the P2Y1R agonist 2-MeSATP in both groups, though it only marginally increased in the infected group. Pre-incubation with the selective P2Y1R antagonist MRS2179 (0.3μM) prevented the agonist effect. However, in the infected group it also reduced the basal leukocyte adhesion, suggesting endothelial cell pre-activation. The endothelial expressions of NTPDases 2 and 3 were significantly increased in the infected group, increasing extracellular ATP hydrolysis and ADP formation by endothelial cells. Therefore, mesenteric endothelial cells are primed by schistosomiasis to a pro-inflammatory phenotype characterized by an increased expression of NTPDases 2 and 3, favoring ADP accumulation and mononuclear cell adhesion, possibly contributing to mesenteric inflammation and schistosomiasis morbidity. PMID:26924460

  17. Lepton flavor violating decays of μ and τ leptons in a gauge group SU(2)L × SU(2)R × SU(2)Y

    NASA Astrophysics Data System (ADS)

    Fayyazuddin

    2016-06-01

    The electroweak unification group SU(2)L × SU(2)R × SU(2)Y is proposed for the charged lepton flavor violating decays of the muon (μ) and tau (τ) leptons. The group SU(2)Y is in the lepton space. The left-handed leptons and antileptons are assigned to the fundamental representation (2, 2,2¯) of the semi-simple group. The gauge group SU(2)Y is spontaneously broken to U(1)Y1, where Y1 = ‑L = ±1 is the hypercharge, by introducing a scalar multiplet Σ which belongs to the triplet representation 3 of the SU(2)Y and is singlet under SU(2)L × SU(2)R. At this stage charged vector bosons Y± of SU(2)Y which mediate the lepton flavor violating decays acquire masses and are decoupled with one Higgs scalar HΣ0. The residual group SU(2)L × SU(2)R × U(1)Y1 has all the features of the left-right electroweak unification group extensively studied in the literature. The probability for lepton flavor violating decays is sin2𝜃W 1‑2sin2𝜃W2 mWL mY4.

  18. Identification and characterization of a novel P2Y 12 variant in a patient diagnosed with type 1 von Willebrand disease in the European MCMDM-1VWD study.

    PubMed

    Daly, Martina E; Dawood, Ban B; Lester, William A; Peake, Ian R; Rodeghiero, Francesco; Goodeve, Anne C; Makris, Michael; Wilde, Jonathan T; Mumford, Andrew D; Watson, Stephen P; Mundell, Stuart J

    2009-04-23

    We investigated whether defects in the P2Y(12) ADP receptor gene (P2RY12) contribute to the bleeding tendency in 92 index cases enrolled in the European MCMDM-1VWD study. A heterozygous mutation, predicting a lysine to glutamate (K174E) substitution in P2Y(12), was identified in one case with mild type 1 von Willebrand disease (VWD) and a VWF defect. Platelets from the index case and relatives carrying the K174E defect changed shape in response to ADP, but showed reduced and reversible aggregation in response to 10 muM ADP, unlike the maximal, sustained aggregation observed in controls. The reduced response was associated with an approximate 50% reduction in binding of [(3)H]2MeS-ADP to P2Y(12), whereas binding to the P2Y(1) receptor was normal. A hemagglutinin-tagged K174E P2Y(12) variant showed surface expression in CHO cells, markedly reduced binding to [(3)H]2MeS-ADP, and minimal ADP-mediated inhibition of forskolin-induced adenylyl cyclase activity. Our results provide further evidence for locus heterogeneity in type 1 VWD. PMID:19237732

  19. 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.

  20. 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. PMID:25492221

  1. 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. PMID:26431688

  2. Stochastic emergence of inflaton fluctuations in a SdS primordial universe with large-scale repulsive gravity from a 5D vacuum

    NASA Astrophysics Data System (ADS)

    Reyes, L. M.; Madriz Aguilar, J. E.; Bellini, M.

    2011-06-01

    We develop a stochastic approach to study scalar-field fluctuations of the inflaton field in an early inflationary universe with a black hole (BH), which is described by an effective 4D Schwarzschild-de Sitter (SdS) metric. This effective 4D metric is the induced metric on a 4D hypersurface, here representing our universe, which is obtained from a 5D Ricci-flat SdS static metric, after implementing a planar coordinate transformation. On this background, we found that at the end of the inflation, the squared fluctuations of the inflaton field are not exactly scale independent and result sensitive to the mass of the BH.

  3. Testing the dx2-y2*-wave pairing symmetry by quasiparticle interference and Knight shift in BiS2-based superconductors

    NASA Astrophysics Data System (ADS)

    Gao, Yi; Zhou, Tao; Huang, Huaixiang; Tong, Peiqing; Wang, Qiang-Hua

    2014-08-01

    The quasiparticle interference (QPI) patterns in BiS2-based superconductors are theoretically investigated by taking into account the spin-orbital coupling and assuming the recently proposed dx2-y2*-wave pairing symmetry. We found two distinct scattering wave vectors whose evolution can be explained based on the evolution of the constant-energy contours. In addition, we also studied the QPI spectra in the conventional s-wave, d-wave, and extended s-wave cases and propose to further measure the Knight shift to distinguish the dx2-y2*-wave pairing from the d-wave one. The QPI spectra as well as the Knight shift presented in this paper can thus be compared with future scanning tunneling microscopy and NMR experiments to test whether the pairing symmetry is dx2-y2* wave in BiS2-based superconductors.

  4. Scan direction induced charging dynamics and the application for detection of gate to S/D shorts in logic devices

    NASA Astrophysics Data System (ADS)

    Lei, Ming; Tian, Qing; Wu, Kevin; Zhao, Yan

    2016-03-01

    Gate to source/drain (S/D) short is the most common and detrimental failure mechanism for advanced process technology development in Metal-Oxide-Semiconductor-Field-Effect-Transistor (MOSFET) device manufacturing. Especially for sub-1Xnm nodes, MOSFET device is more vulnerable to gate-S/D shorts due to the aggressive scaling. The detection of this kind of electrical short defect is always challenging for in-line electron beam inspection (EBI), especially new shorting mechanisms on atomic scale due to new material/process flow implementation. The second challenge comes from the characterization of the shorts including identification of the exact shorting location. In this paper, we demonstrate unique scan direction induced charging dynamics (SDCD) phenomenon which stems from the transistor level response from EBI scan at post metal contact chemical-mechanical planarization (CMP) layers. We found that SDCD effect is exceptionally useful for gate-S/D short induced voltage contrast (VC) defect detection, especially for identification of shorting locations. The unique SDCD effect signatures of gate-S/D shorts can be used as fingerprint for ground true shorting defect detection. Correlation with other characterization methods on the same defective location from EBI scan shows consistent results from various shorting mechanism. A practical work flow to implement the application of SDCD effect for in-line EBI monitor of critical gate-S/D short defects is also proposed, together with examples of successful application use cases which mostly focus on static random-access memory (SRAM) array regions. Although the capability of gate-S/D short detection as well as expected device response is limited to passing transistors and pull-down transistors due to the design restriction from standard 6-cell SRAM structure, SDCD effect is proven to be very effective for gate-S/D short induced VC defect detection as well as yield learning for advanced technology development.

  5. Thermal expansion of the Paintbrush tuff recovered from borehole USW SD-12 at pressures 30 MPa: Data report

    SciTech Connect

    Martin, R.J.; Noel, J.S.; Boyd, P.J.; Riggins, M.; Price, R.H.

    1997-09-01

    Experimental results are presented for 24 thermal expansion experiments performed on 5 welded specimens of the Paintbrush tuff recovered from borehole USW SD-12 at Yucca Mountain, Nevada. The thermal expansion experiments were performed at constant confining pressures between 1 and 30 MPa. On three specimens, the highest confining pressure measurements were performed first to inhibit thermally induced damage which might occur at lower confining pressures. At each confining pressure two complete thermal cycles were performed. The specimens were heated (to a nominal temperature of 250 C) and cooled at the nominal rate of 0.319 C per minute. The change in specimen length as a function of temperature was measured with two linear variable displacement transducers mounted on endcaps secured to the specimen. The strain increases with increasing temperature and the strain vs temperature curves are concave upward. On cooling, there is hysteresis at the higher temperatures at all confining pressures. The first heating/cooling cycle is anomalous; hysteresis is pronounced, and a permanent shortening of the specimen is observed at the termination of the cycle. The magnitude of the effect was similar for all five specimens regardless of whether the first cycle was carried out at the highest or lowest confining pressure. For subsequent cycles at all confining pressures, no permanent strain develops, and the strain versus temperature curves re very similar. The mean coefficients of thermal expansion ({alpha}) range from 7.9 to 10.8{sup {minus}6} C{sup {minus}1} at temperatures below 100 C, to 14.2 to 20.6 x 10{sup {minus}6} C{sup {minus}1} at temperatures approaching 250 C. The effect of confining pressure on thermal expansion is small. For temperatures above 175 C, the mean coefficients of thermal expansion decreases by 10--12% as the pressure increases from 1 to 30 MPa.

  6. 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

  7. 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. PMID:26424247

  8. Effect of Cage Space on Behavior and Reproduction in Crl:CD(SD) and BN/Crl Laboratory Rats

    PubMed Central

    Gaskill, Brianna N; Pritchett-Corning, Kathleen R

    2015-01-01

    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 cm2, 758 cm2, 903 cm2, or 1355 cm2) 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. PMID:26424247

  9. Six week swimming followed by acute uptakes of ginsenoside Rg1 may affect aerobic capacity of SD rats

    PubMed Central

    Haam, Saebom; Park, Hyon

    2015-01-01

    [Purpose] The purpose of this study is to examine the effects of six-weeks of endurance swim training and short-term intake of Rg1 on the expression of related proteins as well as improvement of aerobic exercise capacity in 8-week-old male SD rats. [Methods] The groups were divided into placebo (NP, n=6), Rg1 (NRG, n=6), exercise+placebo (EP, n=7), and exercise+Rg1 (ERG, n=7). On completion of the 6-week swimming exercise, Rg1-intake groups were treated with acute uptakes (3 times within 24hrs) of Rg1. After the treatment, all groups were subjected to a swim to exhaustion test, and then the mass of muscle tissue, mRNA expression level and activity of citrate synthase (CS) were analyzed on plantaris. [Results] There were no differences in the effect of 6-week swimming exercise and short-term intake of Rg1 on body weight and muscle mass between groups. Although the CS mRNA expression was elevated in the exercise group and combined treatment group, there was no significant difference in CS activity. Acute uptakes of Rg1 did not affect swimming time to exhaustion, but it was increased by 235% and 314% by the 6-weeks of exercise and combined treatment of exercise and Rg1, respectively, which suggests that the combined treatment increased the effect on the capacity of aerobic exercise. [Conclusion] Based on these results, it was confirmed that even a short-term treatment of Rg1 can give an additive effect for improvement of exercise function, and additional studies are needed for the mechanisms and modes of its working. PMID:27274464

  10. 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.

  11. 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.

  12. 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.

  13. P2Y2 receptor-mediated lymphotoxin-α secretion regulates intercellular cell adhesion molecule-1 expression in vascular smooth muscle cells.

    PubMed

    Seye, Cheikh I; Agca, Yuksel; Agca, Cansu; Derbigny, Wilbert

    2012-03-23

    The proinflammatory cytokine lymphotoxin-α (LTA) is thought to contribute to the pathogenesis of atherosclerosis. However, the mechanisms that regulate its expression in vascular smooth muscle cells (VSMC) are poorly understood. The ability of exogenous nucleotides to stimulate LTA production was evaluated in VSMC by ELISA. The P2Y(2) nucleotide receptor (P2Y(2)R) agonist UTP stimulates a strong and sustained release of LTA from WT but not P2Y(2)R(-/-) SMC. Assessment of LTA gene transcription by LTA promoter-luciferase construct indicated that LTA levels are controlled at the level of transcription. We show using RNAi techniques that knockdown of the actin-binding protein filamin-A (FLNa) severely impaired nucleotide-induced Rho activation and consequent Rho-mediated LTA secretion. Reintroduction of FLNa in FLNa RNAi SMC rescued UTP-induced LTA expression. In addition, we found that UTP-stimulated LTA secretion is not sensitive to brefeldin A, which blocks the formation of vesicles involved in protein transport from the endoplasmic reticulum to the Golgi apparatus, suggesting that P2Y(2)R/filamin-mediated secretion of LTA is independent of the endoplasmic reticulum/Golgi secretory vesicle route. Furthermore, UTP selectively induces ICAM-1 expression in WT but not SMC expressing a truncated P2Y(2)R deficient in LTA secretion. These data suggest that P2Y(2)R recruits FLNa to provide a cytoskeletal scaffold necessary for Rho signaling pathway upstream of LTA release and subsequent stimulation of ICAM-1 expression on vascular smooth muscle cells. PMID:22298782

  14. 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

  15. 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. PMID:26869885

  16. IL-1ra Secreted by ATP-Induced P2Y2 Negatively Regulates MUC5AC Overproduction via PLCβ3 during Airway Inflammation

    PubMed Central

    Kim, Jiwook; Kim, Bokyoum; Kim, Joowon; Shin, Yusom; Kim, Judeok; Ryu, Siejeong; Yang, Yu-Mi

    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 Ca2+ 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. PMID:27034593

  17. 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.

  18. 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...

  19. 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...

  20. LONG-TERM SD-OCT/SLO IMAGING OF NEURORETINA AND RETINAL PIGMENT EPITHELIUM AFTER SUB-THRESHOLD INFRARED LASER TREATMENT OF DRUSEN

    PubMed Central

    MOJANA, FRANCESCA; BRAR, MANPREET; CHENG, LINGYUN; BARTSCH, DIRK-UWE G.; FREEMAN, WILLIAM R.

    2012-01-01

    PURPOSE To determine the long-term effect of sub-threshold diode laser treatment for drusen in patients with non-exudative age-related macular degeneration (AMD) with spectral domain optical coherence tomography combined with simultaneous scanning laser ophthalmoscope (SD-OCT/SLO). METHODS 8 eyes of 4 consecutive AMD patients with bilateral drusen previously treated with sub-threshold diode laser were imaged with SD-OCT/SLO. Abnormalities in the outer retina layers reflectivity as seen with SD-OCT/SLO were retrospectively analyzed and compared with color fundus pictures and autofluorescence images (AF) acquired immediately before and after the laser treatment. RESULTS A focal discrete disruptions in the reflectivity of the outer retinal layers was noted in 29% of the laser lesions. The junction in between the inner and outer segment of the photoreceptor was more frequently affected, with associated focal damage of the outer nuclear layer. Defects of the RPE were occasionally detected. These changes did not correspond to threshold burns on color fundus photography, but corresponded to focal areas of increased AF in the majority of the cases. CONCLUSIONS Sub-threshold diode laser treatment causes long-term disruption of the retinal photoreceptor layer as analyzed by SD-OCT/SLO. The concept that sub-threshold laser treatment can achieve a selected RPE effect without damage to rods and cones may be flawed. PMID:21157398

  1. Detailed Morphological Changes of Foveoschisis in Patient with X-Linked Retinoschisis Detected by SD-OCT and Adaptive Optics Fundus Camera.

    PubMed

    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

  2. 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

  3. An Analysis on Teachers' Politeness Strategy and Student's Compliance in Teaching Learning Process at SD Negeri 024184 Binjai Timur Binjai--North Sumatra-Indonesia

    ERIC Educational Resources Information Center

    Manik, Sondang; Hutagaol, Juniati

    2015-01-01

    This study aims to find out the politeness strategies used by the teachers and how the politeness affects to the student's compliance. The focus is on directive and expressive speech acts. The subjects of this study were two teachers and the students of class II-A and II-B at SD 024184 Binjai Timur Binjai. The data was gathered by video audio…

  4. Automated geographic atrophy segmentation for SD-OCT images using region-based C-V model via local similarity factor

    PubMed Central

    Niu, Sijie; de Sisternes, Luis; Chen, Qiang; Leng, Theodore; Rubin, Daniel L.

    2016-01-01

    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. PMID:26977364

  5. Evaluation of SD BIOLINE Syphilis 3.0 for Rapid Diagnosis of Syphilis: Report from a Regional Sexually Transmitted Infection Reference Laboratory in North India

    PubMed Central

    Mehra, Bhanu; Bhattar, Sonali; Saxena, Shikhar; Rawat, Deepti; Bhalla, Preena

    2016-01-01

    Background: Serology is considered the mainstay of syphilis diagnosis. The limitations of the traditional serological methods and the advent and availability of novel immunochromatographic assays have led to the widespread application of rapid point-of-care procedures as screening tools for syphilis. However, these tests have not been extensively evaluated. This study was designed to evaluate the performance of a rapid syphilis diagnostic test known as SD BIOLINE Syphilis 3.0 (SD Biostandard Diagnostics Private Limited, Gurgaon, Haryana, India). Materials and Methods: A panel comprising of 50 venereal disease research laboratory reactive and 50 nonreactive sera was tested using SD BIOLINE Syphilis 3.0. The performance of the test was evaluated using IMMUTREP Treponema pallidum hemagglutination assay (TPHA) (OMEGA Diagnostics Limited, Scotland, United Kingdom) as the reference standard and sensitivity, specificity, and negative and positive predictive values were calculated. Results: The sensitivity, specificity, and positive and negative predictive values of SD BIOLINE Syphilis 3.0 were 92.86% (confidence interval of 95%: 80.52–98.50%), 98.28% (90.76-99.96%), 97.50% (86.84–99.94%), and 95.00% (86.08–98.96%), respectively, compared to TPHA as the gold standard. Conclusion: Keeping in view the high sensitivity and specificity of SD BIOLINE Syphilis 3.0, we conclude that the test can be used as a tool for rapid on-site diagnosis of syphilis and as an alternative to TPHA for detection of antibodies to Treponema pallidum. PMID:27013811

  6. Toward a consistent model of the B0.5IVe + sdO binary φ Persei.

    NASA Astrophysics Data System (ADS)

    Bozic, H.; Harmanec, P.; Horn, J.; Koubsky, P.; Scholz, G.; McDavid, D.; Hubert, A.-M.; Hubert, H.

    1995-12-01

    A detailed analysis of a very rich collection of spectroscopic and photometric observations of the bright Be star φ Per is presented. Earlier reports that φ Per is a double-lined spectroscopic binary consisting of two emission-line objects are confirmed. An orbital solution based on the emission-wing radial velocities for both stars has led to a determination of the orbital elements which defines the correct orbital phases. All data since the beginning of this century can be reconciled with a constant orbital period of 126.6731d+/-0.0071d. The new orbital solution gives lower masses than those found by earlier investigators, namely M_1_sin^3^i=16.35Msun_ and M_2_sin^3^i=1.69Msun_. These masses are in agreement with the recently derived spectral classes B0.5IVe and sdO6: for the primary and secondary, respectively. Long-term light variations are positively correlated with the emission strength, and in the U-B vs. B-V diagram the object has changed its apparent photometric type from a B supergiant toward an MS object. Dereddening of the mean seasonal UBV magnitudes from recent years (when spectra show the weakest recorded Balmer emission) leads to a photometric spectral type a bit earlier than B1V. An important and exciting finding is that the emission lines of both stars have been weakening simultaneously in recent years, which seems to indicate some kind of interaction between the binary components. The presence of rapid light variability is confirmed, but its more detailed analysis is postponed for another study. Low-amplitude orbital light variations with rather complicated light and color curves are found after the removal of long-term and rapid changes. The principal maxima and minima of the orbital light curves can be traced in both old and new photometry and can probably be attributed to specific circumstellar structures whose signatures are also seen spectroscopically. Finally, systematic secular changes in the shape and amplitude of the orbital radial

  7. Magnetic Characterization of Synthetic SD-like Pyrrhotite and Its Demagnetization under Hydrostatic Pressure up to 1.8 GPa

    NASA Astrophysics Data System (ADS)

    Bezaeva, N. S.; Chareev, D. A.; Rochette, P.; Kars, M.; Gattacceca, J.

    2014-12-01

    Monoclinic pyrrhotite (Fe7S8) is a common ferrimagnetic mineral in both terrestrial rocks and meteorites (e.g., SNC, Rumuruti chondrites…). It is also recognized as a candidate magnetic mineral for Martian magnetic anomalies. We synthesized SD-like monoclinic pyrrhotite at 245°C using the molten-salt synthesis method [1]. Here we characterize its magnetic properties including its behavior under hydrostatic pressure up to 1.8 GPa. Data were collected in the 10K to 360°C temperature range and include measurements of low-field magnetic susceptibility (χ0), thermomagnetic curves χ0(T), major hysteresis loops, back-field remanence demagnetization curves, first-order reversal curve (FORC), alternating field and pressure demagnetization of saturation isothermal remanent magnetization (SIRM or Mrs), low temperature MPMS datasets (field and frequency dependencies of χ0, field-cooled and zero-field-cooled remanence FC-ZFC and room temperature SIRM heating-cooling cycles) as well as X-ray diffraction (XRD) spectra. χ0(T) indicates a single Curie point at 320°C characteristic of monoclinic pyrrhotite. For application of hydrostatic pressure up to 1.8 GPa we used a nonmagnetic high-pressure cell of piston-cylinder type entirely made of "Russian alloy" (Ni57Cr40Al3) with 8 mm of inner diameter similar to the cell, described in [2]. Application of 1.8 GPa resulted in demagnetization (decrease in SIRM) of the sample by 38%. Repeated cycling from 1.8 GPa to atmospheric pressure and back resulted in further decrease in remanence by 44% (for 3 cycles). The characteristic Besnus transition of pyrrhotite is observed at ~34 K. The observed hysteresis parameters (Mrs/Ms=0.53, Bcr/Bc=1.17, Bcr=41 mT, where Ms is saturation magnetization, Bc and Bcr are coercivity and remanent coercivity, respectively) are consistent with pseudo-single-domain range, previously established in literature [3]. Superparamagnetic (SP) grains are not present in the sample as no frequency dependence of

  8. 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

  9. The phases and magnetic properties of (Ti, Co), and Cr doped Zn 2Y-type hexagonal ferrite

    NASA Astrophysics Data System (ADS)

    Chang, Y. H.; Wang, C. C.; Chin, T. S.; Yen, F. S.

    1988-04-01

    The phases and magnetic properties of Y-type hexagonal ferrite, Ba 2Zn 2 (Ti, Co) yFe 12-2 yO 22 doped with two sets of ions, (Ti, Co) and Cr were studied. In (Ti, Co) - doped ferrites the second phase appears at y ⩾ 0.6, which is a spinel type with the formula of (Zn 1-ηCo η)(Fe 2-δCo δ)O 4. Two resonant peaks are observed in ESR studies at the fields of 1020 and 2430 Oe, respectively, at a frequency of 9.684 GHz. The linewidth increases with the addition of the dopants. In chromium doped ferrite, two phases are identified as the amount of chromium is up to 0.2: spinel type of Zn(Fe 2-ɛCr ɛ)O 4 and orthorhombic BaCr 2O 4. Although the amount of Cr used does not influence the resonant field of the unique peak of the derivative curves from ESR, it eventually enlarges the linewidth.

  10. 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

  11. Origin of the Higher-Tc Phase in the KxFe2-ySe2 System

    NASA Astrophysics Data System (ADS)

    Tanaka, Masashi; Yanagisawa, Yusuke; Denholme, Saleem J.; Fujioka, Masaya; Funahashi, Shiro; Matsushita, Yoshitaka; Ishizawa, Nobuo; Yamaguchi, Takahide; Takeya, Hiroyuki; Takano, Yoshihiko

    2016-04-01

    Single crystals of KxFe2-ySe2 are prepared by quenching at various temperatures. The crystals obtained at higher quenching temperatures have a surface morphology with mesh-like texture. They show a sharp superconducting transition at Tc ˜ 32 K with a large shielding volume fraction. On the other hand, the crystals prepared without quenching show an onset superconducting transition at ˜44 K and a zero resistivity at approximately ˜33 K, and they possess island-like regions on the surface with a larger amount of Fe incorporation. In situ high-temperature single-crystal X-ray diffraction measurements tell us the Fe-vacancy-ordered phase is generated at a temperature region of around 270 °C via iron diffusion. The generation of this Fe-vacancy-ordered phase may become a driving force for the growth of the higher-Tc phase. The superconductivity at ˜44 K is attributed to a metallic phase with no Fe vacancy.

  12. Thermodynamic stability analysis of isometric and elongated epitaxial Ce1-xGdxO2-y nanostructures on perovskite substrates

    NASA Astrophysics Data System (ADS)

    Gibert, Marta; García, Alberto; Puig, Teresa; Obradors, Xavier

    2010-10-01

    The identification of the equilibrium shape of strain-induced nanostructures plays a key role for the nanoengineering of many materials. In this paper, thermodynamic analyses are used to model the observed different shapes of epitaxially grown Ce1-xGdxO2-y (CGO) nanoislands on oxide perovskite single-crystals substrates. We investigate the role of modified biaxial strain arising from islands with different crystallographic orientations. We show that the in-plane lateral aspect ratio (isomorphic, anisotropic) of the interfacial nanoislands can be tuned through the strains with the thermodynamic results reported being consistent with the shapes and sizes experimentally observed. The equilibrium shape of isotropic-strained (001)CGO nanoislands corresponds, within the investigated sizes, to square-based nanopyramids and they have a stable size. Instead, the strain anisotropy of (011)CGO nanoislands is proved to be essential to explain their high shape anisotropy, which increases continuously with island coarsening as a mechanism to minimize their energy density. This model sheds light on the key parameters involved in a very general approach for the generation of epitaxial nanowires.

  13. Noncompetitive Counteractions of DNA Polymerase ɛ and ISW2/yCHRAC for Epigenetic Inheritance of Telomere Position Effect in Saccharomyces cerevisiae

    PubMed Central

    Iida, Tetsushi; Araki, Hiroyuki

    2004-01-01

    Relocation of euchromatic genes near the heterochromatin region often results in mosaic gene silencing. In Saccharomyces cerevisiae, cells with the genes inserted at telomeric heterochromatin-like regions show a phenotypic variegation known as the telomere-position effect, and the epigenetic states are stably passed on to following generations. Here we show that the epigenetic states of the telomere gene are not stably inherited in cells either bearing a mutation in a catalytic subunit (Pol2) of replicative DNA polymerase ɛ (Pol ɛ) or lacking one of the nonessential and histone fold motif-containing subunits of Pol ɛ, Dpb3 and Dpb4. We also report a novel and putative chromatin-remodeling complex, ISW2/yCHRAC, that contains Isw2, Itc1, Dpb3-like subunit (Dls1), and Dpb4. Using the single-cell method developed in this study, we demonstrate that without Pol ɛ and ISW2/yCHRAC, the epigenetic states of the telomere are frequently switched. Furthermore, we reveal that Pol ɛ and ISW2/yCHRAC function independently: Pol ɛ operates for the stable inheritance of a silent state, while ISW2/yCHRAC works for that of an expressed state. We therefore propose that inheritance of specific epigenetic states of a telomere requires at least two counteracting regulators. PMID:14673157

  14. X1X1X2X2/X1X2Y sex chromosome systems in the Neotropical Gymnotiformes electric fish of the genus Brachyhypopomus.

    PubMed

    Cardoso, Adauto Lima; Pieczarka, Julio Cesar; Nagamachi, Cleusa Yoshiko

    2015-05-01

    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

  15. Dual Modulation of Nociception and Cardiovascular Reflexes during Peripheral Ischemia through P2Y1 Receptor-Dependent Sensitization of Muscle Afferents

    PubMed Central

    Queme, Luis F.; Ross, Jessica L.; Lu, Peilin; Hudgins, Renita C.

    2016-01-01

    Numerous musculoskeletal pain disorders are based in dysfunction of peripheral perfusion and are often comorbid with altered cardiovascular responses to muscle contraction/exercise. We have recently found in mice that 24 h peripheral ischemia induced by a surgical occlusion of the brachial artery (BAO) induces increased paw-guarding behaviors, mechanical hypersensitivity, and decreased grip strength. These behavioral changes corresponded to increased heat sensitivity as well as an increase in the numbers of chemosensitive group III/IV muscle afferents as assessed by an ex vivo forepaw muscles/median and ulnar nerves/dorsal root ganglion (DRG)/spinal cord (SC) recording preparation. Behaviors also corresponded to specific upregulation of the ADP-responsive P2Y1 receptor in the DRGs. Since group III/IV muscle afferents have separately been associated with regulating muscle nociception and exercise pressor reflexes (EPRs), and P2Y1 has been linked to heat responsiveness and phenotypic switching in cutaneous afferents, we sought to determine whether upregulation of P2Y1 was responsible for the observed alterations in muscle afferent function, leading to modulation of muscle pain-related behaviors and EPRs after BAO. Using an afferent-specific siRNA knockdown strategy, we found that inhibition of P2Y1 during BAO not only prevented the increased mean blood pressure after forced exercise, but also significantly reduced alterations in pain-related behaviors. Selective P2Y1 knockdown also prevented the increased firing to heat stimuli and the BAO-induced phenotypic switch in chemosensitive muscle afferents, potentially through regulating membrane expression of acid sensing ion channel 3. These results suggest that enhanced P2Y1 in muscle afferents during ischemic-like conditions may dually regulate muscle nociception and cardiovascular reflexes. SIGNIFICANCE STATEMENT Our current results suggest that P2Y1 modulates heat responsiveness and chemosensation in muscle afferents

  16. G protein-coupled estrogen receptor inhibits the P2Y receptor-mediated Ca(2+) signaling pathway in human airway epithelia.

    PubMed

    Hao, Yuan; Chow, Alison W; Yip, Wallace C; Li, Chi H; Wan, Tai F; Tong, Benjamin C; Cheung, King H; Chan, Wood Y; Chen, Yangchao; Cheng, Christopher H; Ko, Wing H

    2016-08-01

    P2Y receptor activation causes the release of inflammatory cytokines in the bronchial epithelium, whereas G protein-coupled estrogen receptor (GPER), a novel estrogen (E2) receptor, may play an anti-inflammatory role in this process. We investigated the cellular mechanisms underlying the inhibitory effect of GPER activation on the P2Y receptor-mediated Ca(2+) signaling pathway and cytokine production in airway epithelia. Expression of GPER in primary human bronchial epithelial (HBE) or 16HBE14o- cells was confirmed on both the mRNA and protein levels. Stimulation of HBE or 16HBE14o- cells with E2 or G1, a specific agonist of GPER, attenuated the nucleotide-evoked increases in [Ca(2+)]i, whereas this effect was reversed by G15, a GPER-specific antagonist. G1 inhibited the secretion of two proinflammatory cytokines, interleukin (IL)-6 and IL-8, in cells stimulated by adenosine 5'-(γ-thio)triphosphate (ATPγS). G1 stimulated a real-time increase in cAMP levels in 16HBE14o- cells, which could be inhibited by adenylyl cyclase inhibitors. The inhibitory effects of E2 or G1 on P2Y receptor-induced increases in Ca(2+) were reversed by treating the cells with a protein kinase A (PKA) inhibitor. These results demonstrated that the inhibitory effects of G1 or E2 on P2Y receptor-mediated Ca(2+) mobilization and cytokine secretion were due to GPER-mediated activation of a cAMP-dependent PKA pathway. This study has reported, for the first time, the expression and function of GPER as an anti-inflammatory component in human bronchial epithelia, which may mediate through its opposing effects on the pro-inflammatory pathway activated by the P2Y receptors in inflamed airway epithelia. PMID:27271044

  17. Metabotropic P2Y receptors inhibit P2X3 receptor-channels via G protein-dependent facilitation of their desensitization

    PubMed Central

    Gerevich, Z; Zadori, Z; Müller, C; Wirkner, K; Schröder, W; Rubini, P; Illes, P

    2007-01-01

    Background and purpose: The aim of the present study was to investigate whether the endogenous metabotropic P2Y receptors modulate ionotropic P2X3 receptor-channels. Experimental approach: Whole-cell patch-clamp experiments were carried out on HEK293 cells permanently transfected with human P2X3 receptors (HEK293-hP2X3 cells) and rat dorsal root ganglion (DRG) neurons. Key results: In both cell types, the P2Y1,12,13 receptor agonist, ADP-β-S, inhibited P2X3 currents evoked by the selective agonist, α,β-methylene ATP (α,β-meATP). This inhibition could be markedly counteracted by replacing in the pipette solution the usual GTP with GDP-β-S, a procedure known to block all G protein heterotrimers. P2X3 currents evoked by ATP, activating both P2Y and P2X receptors, caused a smaller peak amplitude and desensitized faster than those currents evoked by the selective P2X3 receptor agonist α,β-meATP. In the presence of intracellular GDP-β-S, ATP- and α,β-meATP-induced currents were identical. Recovery from P2X3 receptor desensitization induced by repetitive ATP application was slower than the recovery from α,β-meATP-induced desensitization. When G proteins were blocked by intracellular GDP-β-S, the recovery from the ATP- and α,β-meATP-induced desensitization were of comparable speed. Conclusions and Implications: Our results suggest that the activation of P2Y receptors G protein-dependently facilitates the desensitization of P2X3 receptors and suppresses the recovery from the desensitized state. Hence, the concomitant stimulation of P2X3 and P2Y receptors of DRG neurons by ATP may result both in an algesic effect and a partly counterbalancing analgesic activity. PMID:17351651

  18. Platelet P2Y12 receptors are involved in the haemostatic effect of notoginsenoside Ft1, a saponin isolated from Panax notoginseng

    PubMed Central

    Gao, B; Huang, L; Liu, H; Wu, H; Zhang, E; Yang, L; Wu, X; Wang, Z

    2014-01-01

    BACKGROUND AND PURPOSE Saponins isolated from Panax notoginseng (Burk.) F.H. Chen have been shown to relieve thrombogenesis and facilitate haemostasis. However, it is not known which saponin accounts for this haemostatic effect. Hence, in the present study we aimed to identify which saponins contribute to its haemostatic activity and to elucidate the possible underlying mechanisms. EXPERIMENTAL APPROACH Platelet aggregation was analysed using a platelet aggregometer. Prothrombin time, activated partial thromboplastin time and thrombin time were measured using a blood coagulation analyser, which was further corroborated with bleeding time and thrombotic assays. The interaction of notoginsenoside Ft1 with the platelet P2Y12 receptor was determined by molecular docking analysis, cytosolic Ca2+ and cAMP measurements, and phosphorylation of PI3K and Akt assays. KEY RESULTS Among the saponins examined, Ft1 was the most potent procoagulant and induced dose-dependent platelet aggregation. Ft1 reduced plasma coagulation indexes, decreased tail bleeding time and increased thrombogenesis. Moreover, it potentiated ADP-induced platelet aggregation and increased cytosolic Ca2+ accumulation, effects that were attenuated by clopidogrel. Molecular docking analysis suggested that Ft1 binds to platelet P2Y12 receptors. The increase in intracellular Ca2+ evoked by Ft1 in HEK293 cells overexpressing P2Y12 receptors could be blocked by ticagrelor. Ft1 also affected the production of cAMP and increased phosphorylation of PI3K and Akt downstream of P2Y12 signalling pathways. CONCLUSION AND IMPLICATIONS Ft1 enhanced platelet aggregation by activating a signalling network mediated through P2Y12 receptors. These novel findings may contribute to the effective utilization of this compound in the therapy of haematological disorders. PMID:24117220

  19. 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

  20. Inhibition of P2Y6 receptor-mediated phospholipase C activation and Ca(2+) signalling by prostaglandin E2 in J774 murine macrophages.

    PubMed

    Ito, Masaaki; Matsuoka, Isao

    2015-02-15

    Extracellular nucleotides act as inflammatory mediators through activation of multiple purinoceptors. Under inflammatory conditions, the purinergic signalling is affected by various inflammatory mediators. We previously showed that prostaglandin (PG) E2 suppressed the elevation of intracellular Ca(2+) concentration ([Ca(2+)]i) stimulated by P2X4, P2Y2, and P2Y6 receptors in J774 murine macrophages. In this study, we examined the mechanism of PGE2 inhibitory effects on P2Y6 receptor-mediated function in J774 cells. The P2Y6 receptor agonist UDP induced a sustained elevation of [Ca(2+)]i by stimulating the phospholipase C (PLC) signalling pathway. PGE2 inhibited [Ca(2+)]i elevation and phosphatidylinositol (PI) hydrolysis in a concentration-dependent manner. J774 cells highly expressed the E-type prostanoid 2 (EP2) receptor subtype, a Gs-coupled receptor. PGE2 and a selective EP2 receptor agonist caused cyclic AMP (cAMP) accumulation in J774 cells. The inhibitory effects of PGE2 on P2Y6 receptor-mediated responses were mimicked by the selective EP2 receptor agonist. Although EP2 receptor is linked to adenylyl cyclase activation, PGE2-induced inhibition of Ca(2+) response and PI hydrolysis could not be mimicked by a lipophilic cAMP derivative, dibutyryl cAMP, or an adenylyl cyclase activator, forskolin. The inhibition of UDP-induced PLC activation by PGE2 was not affected by down-regulation of protein kinase C by phorbol-12-myristate-13-acetate treatment. PGE2 inhibited PLC activation induced by aluminium fluoride, but not by the Ca(2+)-ionophore, ionomycin. Finally, the inhibition of UDP-induced PLC activation by PGE2 was impaired by Gs knockdown using siRNA. These results suggest that EP2 receptor activation in macrophages negatively controls the Gq/11-PLC signalling through a Gs-mediated, but cAMP-independent signalling mechanism. PMID:25614334

  1. The hypolipidemic drug metabolites nafenopin-CoA and ciprofibroyl-CoA are competitive P2Y1 receptor antagonists.

    PubMed

    Coddou, Claudio; Loyola, Gloria; Boyer, José Luis; Bronfman, Miguel; Huidobro-Toro, J Pablo

    2003-02-11

    Coenzyme A (CoA-SH), endogenous and drug-derived CoA-derivatives were tested as putative antagonists of P2Y receptors expressed in Xenopus laevis oocytes, a method used to determine calcium-activated chloride current, an indicator of the activation of these receptors. CoA-SH antagonized reversibly and in a concentration-dependent manner the ATP-gated currents evoked by the human P2Y(1) but not the P2Y(2) receptor. Palmitoyl-CoA was four-fold more potent than CoA-SH as an antagonist while palmitoyl-carnitine was inactive, highlighting the role of the CoA-SH moiety in the antagonism. The CoA derivatives of nafenopin and ciprofibrate, two clinically relevant hypolipidemic drugs, increased 13 and three-fold the potency of CoA-SH, respectively. The K(B)s of nafenopin-CoA and ciprofibroyl-CoA were 58 and 148 nM, respectively; the slopes of the Schild plots were unitary. Neither 100 microM nafenopin nor ciprofibrate alone altered the P2Y(1) receptor activity. Neither CoA-SH nor ciprofibroyl-CoA antagonized the rat P2X(2) or the P2X(4) nucleotide receptors nor interacted with the 5-HT(2A/C) receptors. The bulky drug CoA-SH derivatives identify a hydrophobic pocket, which may serve as a potential target for novel selective P2Y(1) antagonists. PMID:12586354

  2. 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

  3. On the 300km discontinuity with Conversion Phases SdP in the Tonga-Fiji Region

    NASA Astrophysics Data System (ADS)

    Zhou, Y.; Sui, Y.

    2011-12-01

    Conversion phases SdP are powerful for retrieving information of velocity interfaces of deep structure of Earth's interior. The high sensitivity seismograph network Japan (Hi-net) has about 800 seismometers which can provide digital waveform data from since 2004 through internet. The difference between the focal depths and the depth of 300 km discontinuity determines the sizes of Fresnel zones at the discontinuity for the waveform data from the seismic network, so seismic waveform of six earthquakes with depths from 145 to 220km between 2004 and 2011 beneath Tonga-Fiji region are retrieved from Hi-net (www.hinet.bosai.go.jp). The magnitudes of the events used are Mb 5.0-5.7 which means there are good signal-noise ratios and relatively simple source time functions. In this study, the focal depths determined with pP phases are provided by EHB database for those before 2006 and www.globalcmt.org for those after that year. After filtering with 0.2-1.0Hz (e.g. Castle and Creager, JGR, 2000) and manually selection, waveform data are divided to 5-8 groups related to the regional locations of seismometers and proceeded with N-th root slant-stack method, then we can get the related vespegram in differential time vs slowness. There are 38 vespegrams for 6 events. From the vespegrams, the conversion phases are picked according to the references of the theoretical values of the differential times and slownesses. The parameters read from vespegrams are inverted with IASP91 model to the depths and locations of conversion points. The conversion points related to 300 km discontinuity are distributed from 302 to 328km in the Fuji-Tonga region. For the vespegrams from one certain event but sub-networks, the depth variation are less than 20 km, mostly are less than 11km. Especially, the depth variation of the event 6 are just 8 km. So in the square region with 200 * 300 km, the lateral variation of the depth of the 300 km discontinuity is relatively small. Comparing with the former

  4. Blockade of peripheral P2Y1 receptors prevents the induction of thermal hyperalgesia via modulation of TRPV1 expression in carrageenan-induced inflammatory pain rats: involvement of p38 MAPK phosphorylation in DRGs.

    PubMed

    Kwon, Soon-Gu; Roh, Dae-Hyun; Yoon, Seo-Yeon; Moon, Ji-Young; Choi, Sheu-Ran; Choi, Hoon-Seong; Kang, Suk-Yun; Han, Ho-Jae; Beitz, Alvin J; Lee, Jang-Hern

    2014-04-01

    Although previous reports have suggested that P2Y1 receptors (P2Y1Rs) are involved in cutaneous nociceptive signaling, it remains unclear how P2Y1Rs contribute to peripheral sensitization. The current study was designed to delineate the role of peripheral P2Y1Rs in pain and to investigate potential linkages to mitogen-activated protein kinase (MAPK) in DRGs and Transient Receptor Potential Vanilloid 1 (TRPV1) expression in a rodent inflammatory pain model. Following injection of 2% carrageenan into the hind paw, expressions of P2Y1 and TRPV1 and the phosphorylation rates of both p38 MAPK and ERK but not JNK were increased and peaked at day 2 post-injection. Blockade of peripheral P2Y1Rs by the P2Y1R antagonist, MRS2500 injection (i.pl, D0 to D2) significantly reduced the induction of thermal hyperalgesia, but not mechanical allodynia. Simultaneously, MRS2500 injections suppressed upregulated TRPV1 expression and DRG p38 phosphorylation, while pERK signaling was not affected. Furthermore, inhibition of p38 activation in the DRGs by SB203580 (a p38 inhibitor, i.t, D0 to D2) prevented the upregulation of TRPV1 and a single i.t injection of SB203580 reversed the established thermal hyperalgesia, but not mechanical allodynia. Lastly, to identify the mechanism of action of P2Y1Rs, we repeatedly injected the P2Y1 agonist, MRS2365 into the naïve rat's hind paw and observed a dose-dependent increase in TRPV1 expression and p38 MAPK phosphorylation. These data demonstrate a sequential role for P2Y1R, p38 MAPK and TRPV1 in inflammation-induced thermal hyperalgesia; thus, peripheral P2Y1Rs activation modulates p38 MAPK signaling and TRPV1 expression, which ultimately leads to the induction of thermal hyperalgesia. PMID:24333674

  5. 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.

  6. Characterization of diadenosine tetraphosphate (Ap4A) binding sites in cultured chromaffin cells: evidence for a P2y site.

    PubMed Central

    Pintor, J.; Torres, M.; Castro, E.; Miras-Portugal, M. T.

    1991-01-01

    1. Diadenosine tetraphosphate (Ap4A) a dinucleotide, which is stored in secretory granules, presents two types of high affinity binding sites in chromaffin cells. A Kd value of 8 +/- 0.65 x 10(-11) M and Bmax value of 5420 +/- 450 sites per cell were obtained for the high affinity binding site. A Kd value of 5.6 +/- 0.53 x 10(-9) M and a Bmax value close to 70,000 sites per cell were obtained for the second binding site with high affinity. 2. The diadenosine polyphosphates, Ap3A, Ap4A, Ap5A and Ap6A, displaced [3H]-Ap4A from the two binding sites, the Ki values being 1.0 nM, 0.013 nM, 0.013 nM and 0.013 nM for the very high affinity binding site and 0.5 microM, 0.13 microM, 0.062 microM and 0.75 microM for the second binding site. 3. The ATP analogues displaced [3H]-Ap4A with the potency order of the P2y receptors, adenosine 5'-O-(2 thiodiphosphate) (ADP-beta-S) greater than 5'-adenylyl imidodiphosphate (AMP-PNP) greater than alpha, beta-methylene ATP (alpha, beta-MeATP), in both binding sites. The Ki values were respectively 0.075 nM, 0.2 nM and 0.75 nM for the very high affinity binding site and 0.125 microM, 0.5 microM and 0.9 microM for the second binding site. PMID:1912985

  7. Disposition and metabolism of ticagrelor, a novel P2Y12 receptor antagonist, in mice, rats, and marmosets.

    PubMed

    Li, Yan; Landqvist, Claire; Grimm, Scott W

    2011-09-01

    Ticagrelor is a reversibly binding and selective oral P2Y(12) antagonist, developed for the prevention of atherothrombotic events in patients with acute coronary syndromes. The disposition and metabolism of [(14)C]ticagrelor was investigated in mice, rats, and marmosets to demonstrate that these preclinical toxicity species showed similar metabolic profiles to human. Incubations with hepatocytes or microsomes from multiple species were also studied to compare with in vivo metabolic profiles. The routes of excretion were similar for both oral and intravenous administration in mice, rats, and marmosets with fecal excretion being the major elimination pathway accounting for 59 to 96% of the total radioactivity administered. Urinary excretion of drug-related material accounted for only 1 to 15% of the total radioactivity administered. Milk samples from lactating rats displayed significantly higher levels of total radioactivity than plasma after oral administration of ticagrelor. This demonstrated that ticagrelor and/or its metabolites were readily transferred into rat milk and that neonatal rats could be exposed to ticagrelor-related compounds via maternal milk. Ticagrelor and active metabolite AR-C124910 (loss of hydroxyethyl side chain) were the major components in plasma from all species studied and similar to human plasma profiles. The primary metabolite of ticagrelor excreted in urine across all species was an inactive metabolite, AR-C133913 (loss of difluorophenylcyclopropyl group). Ticagrelor, AR-C124910, and AR-C133913 were the major components found in feces from the three species examined. Overall, in vivo metabolite profiles were qualitatively similar across all species and consistent with in vitro results. PMID:21670219

  8. Cesium vacancy ordering in phase-separated C sxF e2 -yS e2

    NASA Astrophysics Data System (ADS)

    Taddei, K. M.; Sturza, M.; Chung, D. Y.; Cao, H. B.; Claus, H.; Kanatzidis, M. G.; Osborn, R.; Rosenkranz, S.; Chmaissem, O.

    2015-09-01

    By simultaneously displaying magnetism and superconductivity in a single phase, the iron-based superconductors provide a model system for the study of magnetism's role in superconductivity. The class of intercalated iron selenide superconductors is unique among these in having the additional property of phase separation and coexistence of two distinct phases—one majority phase with iron vacancy ordering and strong antiferromagnetism, and the other a poorly understood minority microscopic phase with a contested structure. Adding to the intrigue, the majority phase has never been found to show superconductivity on its own while the minority phase has never been successfully synthesized separate from the majority phase. In order to better understand this minority phase, a series of high-quality C sxF e2 -yS e2 single crystals with (0.8 ≤x ≤1 ; 0 ≤y ≤0.3 ) were grown and studied. Neutron and x-ray powder diffraction performed on ground crystals show that the average I 4 /m m m structure of the minority phase is distinctly different from the high-temperature I 4 /m m m parent structure. Moreover, single-crystal diffraction reveals the presence of discrete superlattice reflections that remove the degeneracy of the Cs sites in both the majority and minority phases and reduce their structural symmetries from body centered to primitive. Group theoretical analysis in conjunction with structural modeling shows that the observed superlattice reflections originate from three-dimensional Cs vacancy ordering. This model predicts a 25 % vacancy of the Cs site in the minority phase which is consistent with the site's refined occupancy. Magnetization measurements performed in tandem with neutron single-crystal diffraction provide evidence that the minority phase is the host of superconductivity. Our results also reveal a superconducting dome in which the superconducting transition temperature varies as a function of the nominal valence of iron.

  9. Production, purification, and characterization of antifungal metabolite from Pseudomonas aeruginosa SD12, a new strain obtained from tannery waste polluted soil.

    PubMed

    Dharni, Seema; Alam, Mansoor; Kalani, Komal; Abdul-Khaliq; Samad, Abdul; Srivastava, Santosh Kumar; Patra, Dharani Dhar

    2012-05-01

    A new strain, SD12, was isolated from tannery waste polluted soil and identified as Pseudomonas aeruginosa on the basis of phenotypic traits and by comparison of 16S rRNA sequences. This bacterium exhibited broad-spectrum antagonistic activity against phytopathogenic fungi. The strain produced phosphatases, cellulases, proteases, pectinases, and HCN and also retained its ability to produce hydroxamate-type siderophore. A bioactive metabolite was isolated from P. aeruginosa SD12 and was characterized as 1-hydroxyphenazine ((1-OH-PHZ) by nuclear magnetic resonance (NMR) spectral analysis. The strain was used as a biocontrol agent against root rot and wilt disease of pyrethrum caused by Rhizoctonia solani. The stain is also reported to increase the growth and biomass of Plantago ovata. The purified compound, 1-hydroxyphenazine, also showed broad-spectrum antagonistic activity towards a range of phytopathogenic fungi, which is the first report of its kind. PMID:22561863

  10. Sd(a)-antigen-like structures carried on core 3 are prominent features of glycans from the mucin of normal human descending colon.

    PubMed Central

    Capon, C; Maes, E; Michalski, J C; Leffler, H; Kim, Y S

    2001-01-01

    This paper describes structural characterization by NMR, MS and degradative studies of mucin glycans from normal human descending colon obtained freshly at autopsy. The saccharides were mainly based on core 3 (GlcNAcbeta1-3GalNAc). Among the terminal saccharide determinants Sd(a)/Cad-antigen-like structures were prominent, and Lewis x, sialyl Lewis x and sulphated Lewis x were found as minor components, whereas blood group H and A antigenic determinants were absent. The saccharides were markedly different from those of mucins from colon cancers or colon cancer cell lines analysed so far, in which cores 1 and 2 are prominent features, and in which various other terminal determinants have been found, but not Sd(a)/Cad. PMID:11577689

  11. Detailed software design of an ultra-parallel ultra-high speed SD-OCT for real-time 4D display at 12 volume/second

    NASA Astrophysics Data System (ADS)

    Hiro-Oka, H.; Choi, D.; Shimizu, K.; Ohbayashi, K.

    2012-01-01

    We report on the software design of an ultra-parallel ultra-high speed spectral domain optical coherence tomography (SD-OCT) system. In our system, optical de-multiplexers divide an interferogram into 320 light every 18.7 GHz frequency, instead of a refractive grating for spectroscopy so far used in conventional SD-OCT. These optical elements enable to get rid of a re-sampling process and contribute to reduce the load of computing. The fast Fourier transform (FFT) is performed by field-programmable gate array (FPGA) and real-time 3D OCT images are created on graphics processing unit (GPU). Our system achieves a real-time 3D OCT image display (4D display) with an A-scan, B-scan, and volume rate of 10 MHz, 4 kHz, and 12 volumes per second, respectively.

  12. Optimization of Cry3A Yields in Bacillus thuringiensis by Use of Sporulation-Dependent Promoters in Combination with the STAB-SD mRNA Sequence

    PubMed Central

    Park, Hyun-Woo; Ge, Baoxue; Bauer, Leah S.; Federici, Brian A.

    1998-01-01

    The insecticidal activity of Bacillus thuringiensis strains toxic to coleopterous insects is due to Cry3 proteins assembled into small rectangular crystals. Toxin synthesis in these strains is dependent primarily upon a promoter that is active in the stationary phase and a STAB-SD sequence that stabilizes the cry3 transcript-ribosome complex. Here we show that significantly higher yields of Cry3A can be obtained by using dual sporulation-dependent cyt1Aa promoters to drive the expression of cry3Aa when the STAB-SD sequence is included in the construct. The Cry3A yield per unit of culture medium obtained with this expression system was 12.7-fold greater than that produced by DSM 2803, the wild-type strain of B. thuringiensis from which Cry3Aa was originally described, and 1.4-fold greater than that produced by NB176, a mutant of the same strain containing two or three copies of cry3Aa, which is the active ingredient of the commercial product Novodor, used for control of beetle pests. The toxicities of Cry3A produced with this construct or the wild-type strain were similar when assayed against larvae of the cottonwood leaf beetle, Chrysomela scripta. The volume of Cry3A crystals produced with cyt1Aa promoters and the STAB-SD sequence was 1.3-fold that of typical bipyramidal Cry1 crystals toxic to lepidopterous insects. The dual-promoter/STAB-SD system offers an additional method for potentially improving the efficacy of insecticides based on B. thuringiensis. PMID:9758822

  13. 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.

  14. 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.

  15. 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

  16. 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 Central

    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 (IC50) 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 (AUClast) 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 AUClast 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 to

  17. Modeling the System Parameters of 2M 1533+3759: A New Longer Period Low-Mass Eclipsing sdB+dM Binary

    NASA Astrophysics Data System (ADS)

    For, B.-Q.; Green, E. M.; Fontaine, G.; Drechsel, H.; Shaw, J. S.; Dittmann, J. A.; Fay, A. G.; Francoeur, M.; Laird, J.; Moriyama, E.; Morris, M.; Rodríguez-López, C.; Sierchio, J. M.; Story, S. M.; Strom, A.; Wang, C.; Adams, S. M.; Bolin, D. E.; Eskew, M.; Chayer, P.

    2010-01-01

    We present new photometric and spectroscopic observations for 2M 1533+3759 (= NSVS 07826147), the seventh eclipsing subdwarf B star + M dwarf (sdB+dM) binary ever found. It has an orbital period of 0.16177042 days, or ~3.88 hr, significantly longer than the 2.3-3.0 hr periods of the other known eclipsing sdB+dM systems. Spectroscopic analysis of the hot primary yields T eff = 29230 ± 125 K, log g = 5.58 ± 0.03, and log N(He)/N(H) = -2.37 ± 0.05. The sdB velocity amplitude is K 1 = 71.1 ± 1.0 km s-1. The only detectable light contribution from the secondary is due to the surprisingly strong reflection effect, whose peak-to-peak BVRI amplitudes are 0.10, 0.13, 0.15, and 0.19 mag, respectively. Light-curve modeling produced several solutions corresponding to different values of the system mass ratio, q (M 2/M 1), but only one is consistent with a core helium burning star, q = 0.301. The orbital inclination is 86fdg6. The sdB primary mass is M 1 = 0.376 ± 0.055 M sun and its radius is R 1 = 0.166 ± 0.007 R sun. 2M 1533+3759 joins PG 0911+456 (and possibly also HS 2333+3927) in having an unusually low mass for an sdB star. SdB stars with masses significantly lower than the canonical value of 0.48 M sun, down to as low as 0.30 M sun, were theoretically predicted by Han et al., but observational evidence has only recently begun to confirm the existence of such stars. The existence of core helium burning stars with masses lower than 0.40-0.43 M sun implies that at least some sdB progenitors have initial main-sequence masses of 1.8-2.0 M sun or more, i.e., they are at least main-sequence A stars. The orbital separation in 2M 1533+3759 is a = 0.98 ± 0.04R sun. The secondary has M 2 = 0.113 ± 0.017 M sun, R 2 = 0.152 ± 0.005R sun, and T_eff_{2} = 3100 ± 600 K, consistent with a main-sequence M5 star. If 2M 1533+3759 becomes a cataclysmic variable (CV), its orbital period will be 1.6 hr, below the CV period gap.

  18. Pnicogen-pnicogen interactions in O2XP:PH2Y complexes (X = H, F, CN; Y = H, OH, OCH3, CH3, NH2)

    NASA Astrophysics Data System (ADS)

    Esrafili, Mehdi D.; Mohammadian-Sabet, Fariba

    2015-10-01

    Pnicogen-pnicogen bonded complexes formed between PO2X (X = H, CN and F) as the Lewis acids and a series of phosphorous bases PH2Y (Y = H, OH, OCH3, CH3 and NH2) are investigated by means of MP2 and M06-2X computational methods. Interaction energies of these complexes are in the range of -11 to -45 kcal/mol at the MP2/aug-cc-pVTZ level. Complexation of PO2X with the PH2Y leads to P…P bonds with a significant degree of covalency. The spin-spin coupling constant across P…P interaction depends on the nature of X and Y substituents. Fermi-contact (FC) term is an excellent approximation to total 1pJ(P-P).

  19. 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

  20. 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

  1. 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. PMID:26053483

  2. Arrestins 2 and 3 differentially regulate ETA and P2Y2 receptor-mediated cell signaling and migration in arterial smooth muscle

    PubMed Central

    Morris, Gavin E.; Nelson, Carl P.; Brighton, Paul J.; Standen, Nicholas B.; Challiss, R. A. John

    2012-01-01

    Overstimulation of endothelin type A (ETA) and nucleotide (P2Y) Gαq-coupled receptors in vascular smooth muscle causes vasoconstriction, hypertension, and, eventually, hypertrophy and vascular occlusion. G protein-coupled receptor kinases (GRKs) and arrestin proteins are sequentially recruited by agonist-occupied Gαq-coupled receptors to terminate phospholipase C signaling, preventing prolonged/inappropriate contractile signaling. However, these proteins also play roles in the regulation of several mitogen-activated protein kinase (MAPK) signaling cascades known to be essential for vascular remodeling. Here we investigated whether different arrestin isoforms regulate endothelin and nucleotide receptor MAPK signaling in rat aortic smooth muscle cells (ASMCs). When intracellular Ca2+ levels were assessed in isolated ASMCs loaded with Ca2+-sensitive dyes, P2Y2 and ETA receptor desensitization was attenuated by selective small-interfering (si)RNA-mediated depletion of G protein-coupled receptor kinase 2 (GRK2). Using similar siRNA techniques, knockdown of arrestin2 prevented P2Y2 receptor desensitization and enhanced and prolonged p38 and ERK MAPK signals, while arrestin3 depletion was ineffective. Conversely, arrestin3 knockdown prevented ETA receptor desensitization and attenuated ET1-stimulated p38 and ERK signals, while arrestin2 depletion had no effect. Using Transwell assays to assess agonist-stimulated ASMC migration, we found that UTP-stimulated migration was markedly attenuated following arrestin2 depletion, while ET1-stimulated migration was attenuated following knockdown of either arrestin. These data highlight a differential arrestin-dependent regulation of ETA and P2Y2 receptor-stimulated MAPK signaling. GRK2 and arrestin expression are essential for agonist-stimulated ASMC migration, which, as a key process in vascular remodeling, highlights the potential roles of GRK2 and arrestin proteins in the progression of vascular disease. PMID:22159081

  3. Arrestins 2 and 3 differentially regulate ETA and P2Y2 receptor-mediated cell signaling and migration in arterial smooth muscle.

    PubMed

    Morris, Gavin E; Nelson, Carl P; Brighton, Paul J; Standen, Nicholas B; Challiss, R A John; Willets, Jonathon M

    2012-03-01

    Overstimulation of endothelin type A (ET(A)) and nucleotide (P2Y) Gα(q)-coupled receptors in vascular smooth muscle causes vasoconstriction, hypertension, and, eventually, hypertrophy and vascular occlusion. G protein-coupled receptor kinases (GRKs) and arrestin proteins are sequentially recruited by agonist-occupied Gα(q)-coupled receptors to terminate phospholipase C signaling, preventing prolonged/inappropriate contractile signaling. However, these proteins also play roles in the regulation of several mitogen-activated protein kinase (MAPK) signaling cascades known to be essential for vascular remodeling. Here we investigated whether different arrestin isoforms regulate endothelin and nucleotide receptor MAPK signaling in rat aortic smooth muscle cells (ASMCs). When intracellular Ca(2+) levels were assessed in isolated ASMCs loaded with Ca(2+)-sensitive dyes, P2Y(2) and ET(A) receptor desensitization was attenuated by selective small-interfering (si)RNA-mediated depletion of G protein-coupled receptor kinase 2 (GRK2). Using similar siRNA techniques, knockdown of arrestin2 prevented P2Y(2) receptor desensitization and enhanced and prolonged p38 and ERK MAPK signals, while arrestin3 depletion was ineffective. Conversely, arrestin3 knockdown prevented ET(A) receptor desensitization and attenuated ET1-stimulated p38 and ERK signals, while arrestin2 depletion had no effect. Using Transwell assays to assess agonist-stimulated ASMC migration, we found that UTP-stimulated migration was markedly attenuated following arrestin2 depletion, while ET1-stimulated migration was attenuated following knockdown of either arrestin. These data highlight a differential arrestin-dependent regulation of ET(A) and P2Y(2) receptor-stimulated MAPK signaling. GRK2 and arrestin expression are essential for agonist-stimulated ASMC migration, which, as a key process in vascular remodeling, highlights the potential roles of GRK2 and arrestin proteins in the progression of vascular disease

  4. 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. PMID:26340851

  5. 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

  6. High Activity of Ce1-xNixO2-y for H2 Production through Ethanol Steam Reforming: Tuning Catalytic Performance through Metal-Oxide Interactions

    SciTech Connect

    G Zhou; L Barrio; S Agnoli; S Senanayake; J Evans; A Kubacka; M Estrella; J Hanson; A Martinez-Arias; et al.

    2011-12-31

    The importance of the oxide: Ce{sub 0.8}Ni{sub 0.2}O{sub 2-y} is an excellent catalyst for ethanol steam reforming. Metal-oxide interactions perturb the electronic properties of the small particles of metallic nickel present in the catalyst under the reaction conditions and thus suppress any methanation activity. The nickel embedded in ceria induces the formation of O vacancies, which facilitate cleavage of the OH bonds in ethanol and water.

  7. P2Y12 Inhibitor Pre-Treatment in Non-ST-Elevation Acute Coronary Syndrome: A Decision-Analytic Model.

    PubMed

    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

  8. Another “String to the Bow” of PJ34, a Potent Poly(ADP-Ribose)Polymerase Inhibitor: An Antiplatelet Effect through P2Y12 Antagonism?

    PubMed Central

    Lechaftois, Marie; Dreano, Elise; Palmier, Bruno; Margaill, Isabelle; Marchand-Leroux, Catherine; Bachelot-Loza, Christilla; Lerouet, Dominique

    2014-01-01

    Background Neuro- and vasoprotective effects of poly(ADP-ribose)polymerase (PARP) inhibition have been largely documented in models of cerebral ischemia, particularly with the potent PARP inhibitor PJ34. Furthermore, after ischemic stroke, physicians are faced with incomplete tissue reperfusion and reocclusion, in which platelet activation/aggregation plays a key role. Data suggest that certain PARP inhibitors could act as antiplatelet agents. In that context, the present in vitro study investigated on human blood the potential antiplatelet effect of PJ34 and two structurally different PARP inhibitors, DPQ and INO-1001. Methods and results ADP concentrations were chosen to induce a biphasic aggregation curve resulting from the successive activation of both its receptors P2Y1 and P2Y12. In these experimental conditions, PJ34 inhibited the second phase of aggregation; this effect was reduced by incremental ADP concentrations. In addition, in line with a P2Y12 pathway inhibitory effect, PJ34 inhibited the dephosphorylation of the vasodilator stimulated phosphoprotein (VASP) in a concentration-dependent manner. Besides, PJ34 had no effect on platelet aggregation induced by collagen or PAR1 activating peptide, used at concentrations inducing a strong activation independent on secreted ADP. By contrast, DPQ and INO-1001 were devoid of any effect whatever the platelet agonist used. Conclusions We showed that, in addition to its already demonstrated beneficial effects in in vivo models of cerebral ischemia, the potent PARP inhibitor PJ34 exerts in vitro an antiplatelet effect. Moreover, this is the first study to report that PJ34 could act via a competitive P2Y12 antagonism. Thus, this antiplatelet effect could improve post-stroke reperfusion and/or prevent reocclusion, which reinforces the interest of this drug for stroke treatment. PMID:25329809

  9. ALIX Regulates the Ubiquitin-Independent Lysosomal Sorting of the P2Y1 Purinergic Receptor via a YPX3L Motif

    PubMed Central

    Dores, Michael R.; Grimsey, Neil J.; Mendez, Francisco; Trejo, JoAnn

    2016-01-01

    Endocytic sorting and lysosomal degradation are integral to the regulation of G protein-coupled receptor (GPCR) function. Upon ligand binding, classical GPCRs are activated, internalized and recycled or sorted to lysosomes for degradation, a process that requires receptor ubiquitination. However, recent studies have demonstrated that numerous GPCRs are sorted to lysosomes independent of receptor ubiquitination. Here, we describe an ubiquitin-independent lysosomal sorting pathway for the purinergic GPCR P2Y1. After activation, P2Y1 sorts to lysosomes for degradation independent of direct ubiquitination that is mediated by a YPX3L motif within the second intracellular loop that serves as a binding site for the adaptor protein ALIX. Depletion of ALIX or site-directed mutation of the YPX3L motif inhibits P2Y1 sorting into the lumen of multivesicular endosomes/lysosomes and degradation. These findings confirm the function of YPX3L motifs as lysosomal targeting sequences for GPCRs and demonstrate that ALIX mediates the ubiquitin-independent degradation of certain GPCRs. PMID:27301021

  10. 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.

  11. Synthesis of SiO{sub 2}/Y{sub 2}O{sub 3}:Eu core-shell materials and hollow spheres

    SciTech Connect

    Liu Guixia; Hong Guangyan . E-mail: gyhang@ns.ciac.jl.cn

    2005-05-15

    The SiO{sub 2}/Y{sub 2}O{sub 3}:Eu core-shell materials and hollow spheres were first synthesized by a template-mediated method. X-ray diffraction patterns indicated that the broadened diffraction peaks result from nanocrystals of Y{sub 2}O{sub 3}:Eu shells and hollow spheres. X-ray photoelectron spectra showed that the Y{sub 2}O{sub 3}:Eu shells are linked with silica cores by Si-O-Y chemical bond. SEM and TEM observ