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Sample records for 10mo sd 2y

  1. Elevated Temperature Tensile Tests on DU–10Mo Rolled Foils

    SciTech Connect

    Schulthess, Jason

    2014-09-01

    Tensile mechanical properties for uranium-10 wt.% molybdenum (U–10Mo) foils are required to support modeling and qualification of new monolithic fuel plate designs. It is expected that depleted uranium-10 wt% Mo (DU–10Mo) mechanical behavior is representative of the low enriched U–10Mo to be used in the actual fuel plates, therefore DU-10Mo was studied to simplify material processing, handling, and testing requirements. In this report, tensile testing of DU-10Mo fuel foils prepared using four different thermomechanical processing treatments were conducted to assess the impact of foil fabrication history on resultant tensile properties.

  2. SEM Characterization of an Irradiated Monolithic U-10Mo Fuel Plate

    SciTech Connect

    D. D. Keiser, Jr.; J. F. Jue; A. B. Robinson

    2010-03-01

    Results of scanning electron microscopy (SEM) characterization of irradiated U-7Mo dispersion fuel plates with differing amounts of matrix Si have been reported. However, to date, no results of SEM analysis of irradiated U-Mo monolithic fuel plates have been reported. This paper describes the first SEM characterization results for an irradiated monolithic U-10Mo fuel plate. Two samples from this fuel plate were characterized. One sample was produced from the low-flux side of the fuel plate, and another was produced at the high-flux side of the fuel plate. This characterization focused on the microstructural features present at the U-10Mo foil/cladding interface, particularly the interaction zone that had developed during fabrication and irradiation. In addition, the microstructure of the foil itself was investigated, along with the morphology of the observed fission gas bubbles. It was observed that a Si-rich interaction layer was present at the U-10Mo foil/cladding interface that exhibited relatively good irradiation behavior, and within the U-10Mo foil the microstructural features differed in some respects from what is typically seen in the U-Mo powders of an irradiated dispersion fuel.

  3. The Microstructure of Rolled Plates from Cast Billets of U-10Mo Alloys

    SciTech Connect

    Nyberg, Eric A.; Joshi, Vineet V.; Burkes, Douglas; Lavender, Curt A.

    2015-03-01

    This report covers the examination of 13 samples of rolled plates from three separate castings of uranium, alloyed with 10 wt% molybdenum (U-10Mo) which were sent from the Y-12 National Security Complex (Y12) to the Pacific Northwest National Laboratory (PNNL).

  4. LANL Experience Rolling Zr-Clad LEU-10Mo Foils for AFIP-7

    SciTech Connect

    Hammon, Duncan L.; Clarke, Kester D.; Alexander, David J.; Kennedy, Patrick K.; Edwards, Randall L.; Duffield, Andrew N.; Dombrowski, David E.

    2015-05-29

    The cleaning, canning, rolling and final trimming of Low Enriched Uranium-10 wt. pct. Molybdenum (LEU-10Mo) foils for ATR (Advanced Test Reactor) fuel plates to be used in the AFIP-7 (ATR Full Size Plate In Center Flux Trap Position) experiments are summarized. Six Zr-clad foils were produced from two LEU-10Mo castings supplied to Los Alamos National Laboratory (LANL) by Y-12 National Security Complex. Details of cleaning and canning procedures are provided. Hot- and cold-rolling results are presented, including rolling schedules, images of foils in-process, metallography and local compositions of regions of interest, and details of final foil dimensions and process yield. This report was compiled from the slides for the presentation of the same name given by Duncan Hammon on May 12, 2011 at the AFIP-7 Lessons Learned meeting in Salt Lake City, UT, with Los Alamos National Laboratory document number LA-UR 11-02898.

  5. Thermal stability of fission gas bubble superlattice in irradiated U–10Mo fuel

    SciTech Connect

    Gan, J.; Keiser, D. D.; Miller, B. D.; Robinson, A. B.; Wachs, D. M.; Meyer, M. K.

    2015-09-01

    To investigate the thermal stability of the fission gas bubble superlattice, a key microstructural feature in both irradiated U-7Mo dispersion and U-10Mo monolithic fuel plates, a FIB-TEM sample of the irradiated U-10Mo fuel with a local fission density of 3.5×1021 fissions/cm3 was used for an in-situ heating TEM experiment. The temperature of the heating holder was raised at a ramp rate of approximately 10 ºC/min up to ~700 ºC, kept at that temperature for about 34 min, continued to 850 ºC with a reduced rate of 5 ºC/min. The result shows a high thermal stability of the fission gas bubble superlattice. The implication of this observation on the fuel microstructural evolution and performance under irradiation is discussed.

  6. Co-Rolled U10Mo/Zirconium-Barrier-Layer Monolithic Fuel Foil Fabrication Process

    SciTech Connect

    G. A. Moore; M. C. Marshall

    2010-01-01

    Integral to the current UMo fuel foil processing scheme being developed at Idaho National Laboratory (INL) is the incorporation of a zirconium barrier layer for the purpose of controlling UMo-Al interdiffusion at the fuel-meat/cladding interface. A hot “co-rolling” process is employed to establish a ~25-µm-thick zirconium barrier layer on each face of the ~0.3-mm-thick U10Mo fuel foil.

  7. Precipitation hardening and microstructure evolution of the Ti-7Nb-10Mo alloy during aging.

    PubMed

    Yi, Ruowei; Liu, Huiqun; Yi, Danqing; Wan, Weifeng; Wang, Bin; Jiang, Yong; Yang, Qi; Wang, Dingchun; Gao, Qi; Xu, Yanfei; Tang, Qian

    2016-06-01

    A biomedical β titanium alloy (Ti-7Nb-10Mo) was designed and prepared by vacuum arc self-consumable melting. The ingot was forged and rolled to plates, followed by quenching and aging. Age-hardening behavior, microstructure evolution and its influence on mechanical properties of the alloy during aging were investigated, using X-ray diffraction, transmission electron microscopy, tensile and hardness measurements. The electrochemical behavior of the alloy was investigated in Ringer's solution. The microstructure of solution-treated (ST) alloy consists of the supersaturated solid solution β phase and the ωath formed during athermal process. The ST alloy exhibits Young's modulus of 80 GPa, tensile strength of 774 MPa and elongation of 20%. The precipitation sequences during isothermal aging at different temperatures were determined as β+ωath→β+ωiso (144 h) at Taging=350-400 °C, β+ωath→β+ωiso+α→β+α at Taging=500°C, and β+ωath→β+α at Taging=600-650 °C, where ωiso forms during isothermal process. The mechanical properties of the alloy can be tailored easily through controlling the phase transition during aging. Comparing with the conventional Ti-6Al-4V alloy, the Ti-7Nb-10Mo alloy is more resistant to corrosion in Ringer's solution. Results show that the Ti-7Nb-10Mo alloy is promising for biomedical applications. PMID:27040253

  8. Effect of commercial mouthwashes on the corrosion resistance of Ti-10Mo experimental alloy.

    PubMed

    Alves Rezende, Maria Cristina Rosifini; Alves, Ana Paula Rosifini; Codaro, Eduardo Norberto; Dutra, Conceição Aparecida Matsumoto

    2007-01-01

    The purpose of this work was to evaluate the effect of three commercial mouthwashes on the corrosion resistance of Ti-10Mo experimental alloy. Experiments were made at 37.0 +/- 0.5 degrees C in a conventional three-compartment double wall glass cell containing commercial mouthwashes. Three mouthwashes with different active ingredients were tested: (I) 0.05% sodium fluoride + 0.03% triclosan; (II) 0.5 g/l cetylpyridinium chloride + 0.05% sodium fluoride; (III) 0.12% chlorohexidine digluconate. The assessment of the individual effect of active ingredients was studied by using 0.05% sodium fluoride. Commercially pure titanium (CP Ti) was used as control. Microstructures from Ti-10Mo experimental alloy and CP Ti were also evaluated using optical microscopy. Ti-10Mo as-cast alloy shows the typical rapidly cooled dendrites microstructure (beta phase) while CP Ti has exhibited a metastable martensitic microstructure. Electrochemical behavior of dental materials here studied was more affected by mouthwash type than by Ti alloy composition or microstructure. In both alloys passivation phenomenon was observed. This process may be mainly related to Ti oxides or other Ti species present in spontaneously formed film. Small differences in passive current densities values may be connected with changes in film porosity and thickness. Protective characteristics of this passive film are lower in 0.05% sodium fluoride + 0.03% triclosan mouthwash than in the other two mouthwashes tested. PMID:17200826

  9. Precipitation hardening and microstructure evolution of the Ti-7Nb-10Mo alloy during aging.

    PubMed

    Yi, Ruowei; Liu, Huiqun; Yi, Danqing; Wan, Weifeng; Wang, Bin; Jiang, Yong; Yang, Qi; Wang, Dingchun; Gao, Qi; Xu, Yanfei; Tang, Qian

    2016-06-01

    A biomedical β titanium alloy (Ti-7Nb-10Mo) was designed and prepared by vacuum arc self-consumable melting. The ingot was forged and rolled to plates, followed by quenching and aging. Age-hardening behavior, microstructure evolution and its influence on mechanical properties of the alloy during aging were investigated, using X-ray diffraction, transmission electron microscopy, tensile and hardness measurements. The electrochemical behavior of the alloy was investigated in Ringer's solution. The microstructure of solution-treated (ST) alloy consists of the supersaturated solid solution β phase and the ωath formed during athermal process. The ST alloy exhibits Young's modulus of 80 GPa, tensile strength of 774 MPa and elongation of 20%. The precipitation sequences during isothermal aging at different temperatures were determined as β+ωath→β+ωiso (144 h) at Taging=350-400 °C, β+ωath→β+ωiso+α→β+α at Taging=500°C, and β+ωath→β+α at Taging=600-650 °C, where ωiso forms during isothermal process. The mechanical properties of the alloy can be tailored easily through controlling the phase transition during aging. Comparing with the conventional Ti-6Al-4V alloy, the Ti-7Nb-10Mo alloy is more resistant to corrosion in Ringer's solution. Results show that the Ti-7Nb-10Mo alloy is promising for biomedical applications.

  10. FULL SIZE U-10MO MONOLITHIC FUEL FOIL AND FUEL PLATE FABRICATION-TECHNOLOGY DEVELOPMENT

    SciTech Connect

    G. A. Moore; J-F Jue; B. H. Rabin; M. J. Nilles

    2010-03-01

    Full-size U10Mo foils are being developed for use in high density LEU monolithic fuel plates. The application of a zirconium barrier layer too the foil is applied using a hot co-rolling process. Aluminum clad fuel plates are fabricated using Hot Isostatic Pressing (HIP) or a Friction Bonding (FB) process. An overview is provided of ongoing technology development activities, including: the co-rolling process, foil shearing/slitting and polishing, cladding bonding processes, plate forming, plate-assembly swaging, and fuel plate characterization. Characterization techniques being employed include, Ultrasonic Testing (UT), radiography, and microscopy.

  11. Thermal cycling effect in U-10Mo/Zry-4 monolithic nuclear fuel

    NASA Astrophysics Data System (ADS)

    Lopes, Denise A.; Zimmermann, Angelo J. O.; Silva, Selma L.; Piqueira, J. R. C.

    2016-05-01

    Uranium alloys in a monolithic form have been considered attractive candidates for high density nuclear fuel. However, this high-density fissile material configuration keeps the volume permitted for the retention of fission products at a minimum. Additionally, the monolithic nuclear fuel has a peculiar configuration, whereby the fuel is in direct contact with the cladding. How this fuel configuration will retain fission products and how this will affect its integrity under various physical conditions - such as thermal cycling - are some of the technological problems for this new fuel. In this paper, the effect of out-of-pile thermal cycling is studied for a monolithic fuel plate produced by a hot co-rolling method using U-10Mo (wt %) as the fuel alloy and Zircaloy-4 as the cladding material. After performing 10 thermal cycles from 25 to 400 °C at a rate of 1 °C/min (∼125 h), the fuel alloy presented several fractures that were observed to occur in the last three cycles. These cracks nucleated approximately in the center of the fuel alloy and crossed the interdiffusion zone initiating an internal crack in the cladding. The results suggest that the origin of these fractures is the thermal fatigue of the U-10Mo alloy caused due to the combination of two factors: (i) the high difference in the thermal expansion coefficient of the fuel and of the cladding material, and (ii) the bound condition of fuel/cladding materials in this fuel element configuration.

  12. Four-point Bend Testing of Irradiated Monolithic U-10Mo Fuel

    SciTech Connect

    Rabin, B. H.; Lloyd, W. R.; Schulthess, J. L.; Wright, J. K.; Lind, R. P.; Scott, L.; Wachs, K. M.

    2015-03-01

    This paper presents results of recently completed studies aimed at characterizing the mechanical properties of irradiated U-10Mo fuel in support of monolithic base fuel qualification. Mechanical properties were evaluated in four-point bending. Specimens were taken from fuel plates irradiated in the RERTR-12 and AFIP-6 Mk. II irradiation campaigns, and tests were conducted in the Hot Fuel Examination Facility (HFEF) at Idaho National Laboratory (INL). The monolithic fuel plates consist of a U-10Mo fuel meat covered with a Zr diffusion barrier layer fabricated by co-rolling, clad in 6061 Al using a hot isostatic press (HIP) bonding process. Specimens exhibited nominal (fresh) fuel meat thickness ranging from 0.25 mm to 0.64 mm, and fuel plate average burnup ranged from approximately 0.4 x 1021 fissions/cm3 to 6.0 x 1021 fissions/cm3. After sectioning the fuel plates, the 6061 Al cladding was removed by dissolution in concentrated NaOH. Pre- and post-dissolution dimensional inspections were conducted on test specimens to facilitate accurate analysis of bend test results. Four-point bend testing was conducted on the HFEF Remote Load Frame at a crosshead speed of 0.1 mm/min using custom-designed test fixtures and calibrated load cells. All specimens exhibited substantially linear elastic behavior and failed in a brittle manner. The influence of burnup on the observed slope of the stress-strain curve and the calculated fracture strength is discussed.

  13. Effects of the foil flatness on irradiation performance of U10Mo monolithic mini-plates

    DOE PAGES

    Ozaltun, Hakan; Medvedev, Pavel G.; Rabin, Barry H.

    2015-09-03

    Monolithic plate-type fuels comprise of a high density, low enrichment, U10Mo fuel foil encapsulated in a cladding material. This concept generates several fabrication challenges such as flatness, centering or thickness variation. There are concerns, if these parameters have implications on overall performance. To investigate these inquiries, the effects of the foil flatness were studied. For this, a representative plate was simulated for an ideal case. The simulations were repeated for additional cases with various foil curvatures to evaluate the effects on the irradiation performance. The results revealed that the stresses and strains induced by fabrication process are not affected bymore » the flatness of the foil. Furthermore, fabrication stresses in the foil are relieved relatively fast in the reactor. The effects of the foil flatness on peak irradiation stressstrains are minimal. There is a slight increase in temperature for the case with maximum curvature. The major impact is on the displacement characteristics. Furthermore, while the case with a flat foil produces a symmetrical swelling, if the foil is curved, more swelling occurs on the thin-cladding side and the plate bows during irradiation.« less

  14. Effects of the foil flatness on irradiation performance of U10Mo monolithic mini-plates

    SciTech Connect

    Ozaltun, Hakan; Medvedev, Pavel G.; Rabin, Barry H.

    2015-09-03

    Monolithic plate-type fuels comprise of a high density, low enrichment, U10Mo fuel foil encapsulated in a cladding material. This concept generates several fabrication challenges such as flatness, centering or thickness variation. There are concerns, if these parameters have implications on overall performance. To investigate these inquiries, the effects of the foil flatness were studied. For this, a representative plate was simulated for an ideal case. The simulations were repeated for additional cases with various foil curvatures to evaluate the effects on the irradiation performance. The results revealed that the stresses and strains induced by fabrication process are not affected by the flatness of the foil. Furthermore, fabrication stresses in the foil are relieved relatively fast in the reactor. The effects of the foil flatness on peak irradiation stressstrains are minimal. There is a slight increase in temperature for the case with maximum curvature. The major impact is on the displacement characteristics. Furthermore, while the case with a flat foil produces a symmetrical swelling, if the foil is curved, more swelling occurs on the thin-cladding side and the plate bows during irradiation.

  15. Concept Feasibility Report for Using Co-Extrusion to Bond Metals to Complex Shapes of U-10Mo

    SciTech Connect

    Lavender, Curt A.; Paxton, Dean M.; Smith, Mark T.; Soulami, Ayoub; Joshi, Vineet V.; Burkes, Douglas

    2013-12-30

    In support of the Convert Program of the U.S. Department of Energy’s National Nuclear Security Administration (DOE/NNSA) Global Threat Reduction Initiative (GTRI), Pacific Northwest National Laboratory (PNNL) has been investigating manufacturing processes for the uranium-10% molybdenum (U-10Mo) alloy plate fuel for the U.S. high-performance research reactors (USHPRR). This report documents the results of PNNL’s efforts to develop the extrusion process for this concept. The approach to the development of a co-extruded complex-shaped fuel has been described and an extrusion of DU-10Mo was made. The initial findings suggest that given the extrusion forces required for processing U-10Mo, the co-extrusion process can meet the production demands of the USHPRR fuel and may be a viable production method. The development activity is in the early stages and has just begun to identify technical challenges to address details such as dimensional tolerances and shape control. New extrusion dies and roll groove profiles have been developed and will be assessed by extrusion and rolling of U-10Mo during the next fiscal year. Progress on the development and demonstration of the co-extrusion process for flat and shaped fuel is reported in this document

  16. Benefits of utilizing CellProfiler as a characterization tool for U–10Mo nuclear fuel

    SciTech Connect

    Collette, R.; Douglas, J.; Patterson, L.; Bahun, G.; King, J.; Keiser, D.; Schulthess, J.

    2015-07-15

    Automated image processing techniques have the potential to aid in the performance evaluation of nuclear fuels by eliminating judgment calls that may vary from person-to-person or sample-to-sample. Analysis of in-core fuel performance is required for design and safety evaluations related to almost every aspect of the nuclear fuel cycle. This study presents a methodology for assessing the quality of uranium–molybdenum fuel images and describes image analysis routines designed for the characterization of several important microstructural properties. The analyses are performed in CellProfiler, an open-source program designed to enable biologists without training in computer vision or programming to automatically extract cellular measurements from large image sets. The quality metric scores an image based on three parameters: the illumination gradient across the image, the overall focus of the image, and the fraction of the image that contains scratches. The metric presents the user with the ability to ‘pass’ or ‘fail’ an image based on a reproducible quality score. Passable images may then be characterized through a separate CellProfiler pipeline, which enlists a variety of common image analysis techniques. The results demonstrate the ability to reliably pass or fail images based on the illumination, focus, and scratch fraction of the image, followed by automatic extraction of morphological data with respect to fission gas voids, interaction layers, and grain boundaries. - Graphical abstract: Display Omitted - Highlights: • A technique is developed to score U–10Mo FIB-SEM image quality using CellProfiler. • The pass/fail metric is based on image illumination, focus, and area scratched. • Automated image analysis is performed in pipeline fashion to characterize images. • Fission gas void, interaction layer, and grain boundary coverage data is extracted. • Preliminary characterization results demonstrate consistency of the algorithm.

  17. Application of U10Mo Fuel for Space Fission Power Applications - White Paper

    SciTech Connect

    James Werner

    2014-07-01

    A novel reactor design has been proposed for space applications to provide hundreds of watts to one or two kilowatts of electrical power. The reactor concept proposed uses the alloy U10Mo (uranium with 10 weight percent molybdenum) as the fuel. This fuel was selected for its high uranium density, high thermal conductivity, and excellent neutronic characteristics for this application. The core is surrounded by a BeO reflector. Heat is carried from the reactor by liquid metal heat pipes. A shadow shield of LiH tungsten is also utilized to reduce the neutron and gamma radiation dose to the rest of the spacecraft. This design represents a best effort at minimizing the complexity of the fission system and reducing the mass of the system. The compact nature of the block UMo core and BeO radial reflector allows the reactor diameter to be as small as practical while still meeting the neutronic and thermal power demands. This directly results in a reduced shield mass since the reactor diameter dictates the footprint of the radiation shield. The use of heat pipes offers a straightforward primary heat transport approach using proven liquid-metal heat pipe technology. Further, the elimination of a liquid core coolant system heat transport components, both at the reactor side and radiator side, contributes to reducing the total part-count and lowering system mass. The proposed reactor is using a fuel that is being developed by DOE, but there are significant differences in the fuels enrichment, operating conditions and the physical shape of the fuel itself. This paper attempts to highlight some of the basic consideration and needs that would be expected to be met in developing this fuel and qualifying it for use.

  18. NUMERICAL SIMULATION FOR MECHANICAL BEHAVIOR OF U10MO MONOLITHIC MINIPLATES FOR RESEARCH AND TEST REACTORS

    SciTech Connect

    Hakan Ozaltun & Herman Shen

    2011-11-01

    This article presents assessment of the mechanical behavior of U-10wt% Mo (U10Mo) alloy based monolithic fuel plates subject to irradiation. Monolithic, plate-type fuel is a new fuel form being developed for research and test reactors to achieve higher uranium densities within the reactor core to allow the use of low-enriched uranium fuel in high-performance reactors. Identification of the stress/strain characteristics is important for understanding the in-reactor performance of these plate-type fuels. For this work, three distinct cases were considered: (1) fabrication induced residual stresses (2) thermal cycling of fabricated plates; and finally (3) transient mechanical behavior under actual operating conditions. Because the temperatures approach the melting temperature of the cladding during the fabrication and thermal cycling, high temperature material properties were incorporated to improve the accuracy. Once residual stress fields due to fabrication process were identified, solution was used as initial state for the subsequent simulations. For thermal cycling simulation, elasto-plastic material model with thermal creep was constructed and residual stresses caused by the fabrication process were included. For in-service simulation, coupled fluid-thermal-structural interaction was considered. First, temperature field on the plates was calculated and this field was used to compute the thermal stresses. For time dependent mechanical behavior, thermal creep of cladding, volumetric swelling and fission induced creep of the fuel foil were considered. The analysis showed that the stresses evolve very rapidly in the reactor. While swelling of the foil increases the stress of the foil, irradiation induced creep causes stress relaxation.

  19. SEM in situ MiniCantilever Beam Bending of U-10Mo/Zr/Al Fuel Elements

    SciTech Connect

    Mook, William; Baldwin, Jon K.; Martinez, Ricardo M.; Mara, Nathan A.

    2014-06-16

    In this work, the fracture behavior of Al/Zr and Zr/dU-10Mo interfaces was measured via the minicantilever bend technique. The energy dissipation rates were found to be approximately 3.7-5 mj/mm2 and 5.9 mj/mm2 for each interface, respectively. It was found that in order to test the Zr/U-10Mo interface, location of the hinge of the cantilever was a key parameter. While this test could be adapted to hot cell use through careful alignment fixturing and measurement of crack lengths with an optical microscope (as opposed to SEM, which was used here out of convenience), machining of the cantilevers via MiniMill in such a way as to locate the interfaces at the cantilever hinge, as well as proper placement of a femtosecond laser notch will continue to be key challenges in a hot cell environment.

  20. 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.

  1. 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.

  2. The Influence of Casting Conditions on the Microstructure of As-Cast U-10Mo Alloys: Characterization of the Casting Process Baseline

    SciTech Connect

    Nyberg, Eric A.; Joshi, Vineet V.; Lavender, Curt A.; Paxton, Dean M.; Burkes, Douglas

    2013-12-13

    Sections of eight plate castings of uranium alloyed with 10 wt% molybdenum (U-10Mo) were sent from Y-12 to the Pacific Northwest National Laboratory (PNNL) for microstructural characterization. This report summarizes the results from this study.

  3. ASSESSMENT OF RESIDUAL STRESSES ON U10MO ALLOY BASED MONOLITHIC MINI-PLATES DURING HOT ISOSTATIC PRESSING

    SciTech Connect

    Hakan Ozaltun; M.-H. Herman Shen

    2011-12-01

    This article presents an assessment of the residual stress field on U10Mo alloy based monolithic fuel plates and their elasto-plastic response to the thermo-mechanical fabrication process. Monolithic plate-type fuel for research and test reactors is a new fuel form proposed and developed by Idaho National Laboratory (INL) to accomplish higher uranium densities in the reactor core and allow multi-fold reduction of fuel enrichment. Identification of the 3D residual field is critical for benchmarking the new design and understanding the overall performance of the new plate-type fuels. To define fuel-cladding stress-strain characteristics, a new thermo-mechanical finite element model was developed. Material properties at high temperatures and material plasticity were considered carefully to improve the accuracy as the Hot Pressing temperature reaches the melting temperature of the cladding material. By using elasto-thermo-plastic material models, it was determined that the cladding material (AL6061-TO) is exposed to tensile stress field and exceeds its proportional limits, while the fuel foil (U10Mo) is under compression and remains below its yield limit. It was shown that the residual stresses would govern the overall behavior of the plates, and therefore, should not be neglected. In particular, the simulations have revealed the existence of stress gradients at the fuel/cladding interface, thus emphasizing the necessity of excellent bonding quality at the bond region for mechanical endurance.

  4. β-type Ti-10Mo-1.25Si-xZr biomaterials for applications in hard tissue replacements.

    PubMed

    Zhan, Yongzhong; Li, Chunliu; Jiang, Wenping

    2012-08-01

    In order to develop new β-type Ti-based biochemical materials, a series of Ti-10Mo-1.25Si-xZr (x=4-13) alloys were designed and prepared using vacuum arc melting method. Phase analysis and microstructural observation showed that all the as cast samples consisted of equiaxed β-Ti phase. With the increase of Zr content, the structure of grain boundary changed from semi-continuous network to denser granular, and the microstructure was refined. The solid solution effect of the β-phase stabilization elements (i.e. Mo, Zr and Si) predominantly determined the mechanical properties. These β-type Ti-10Mo-1.25Si-xZr biomaterials exhibited a good combination of high compressive strength, high yield stress, good plasticity, as well as rather low Young's modulus (in the range of 23.086 GPa-32.623 GPa), which may offer potential advantages in the applications in hard tissue replacements (HTRs). PMID:24364974

  5. 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.

  6. Demonstration of femtosecond laser ablation inductively coupled plasma mass spectrometry for uranium isotopic measurements in U-10Mo nuclear fuel foils

    SciTech Connect

    Havrilla, George Joseph; Gonzalez, Jhanis

    2015-06-10

    The use of femtosecond laser ablation inductively coupled plasma mass spectrometry was used to demonstrate the feasibility of measuring the isotopic ratio of uranium directly in U-10Mo fuel foils. The measurements were done on both the flat surface and cross sections of bare and Zr clad U-10Mo fuel foil samples. The results for the depleted uranium content measurements were less than 10% of the accepted U235/238 ratio of 0.0020. Sampling was demonstrated for line scans and elemental mapping over large areas. In addition to the U isotopic ratio measurement, the Zr thickness could be measured as well as trace elemental composition if required. A number of interesting features were observed during the feasibility measurements which could provide the basis for further investigation using this methodology. The results demonstrate the feasibility of using fs-LA-ICP-MS for measuring the U isotopic ratio in U-10Mo fuel foils.

  7. Assessment of residual stresses on U10Mo alloy based monolithic mini-plates during Hot Isostatic Pressing

    NASA Astrophysics Data System (ADS)

    Ozaltun, Hakan; Herman Shen, M.-H.; Medvedev, Pavel

    2011-12-01

    This article presents an assessment of the residual stresses in U-10 wt.% Mo (U10Mo) alloy based monolithic fuel plates and the elasto-plastic response to thermo-mechanical processing. Monolithic, plate-type fuel is a new fuel form being developed for research and test reactors to achieve higher uranium densities within the reactor core to allow the use of low-enriched uranium fuel in high-performance reactors. Understanding of the three-dimensional residual stress field is important for understanding the in-reactor performance of these plate-type fuels. To define fuel-cladding stress-strain characteristics, a thermo-mechanical finite element model was developed. During fuel plate fabrication, the hot pressing temperature approaches the melting temperature of the cladding, so that temperature dependent material properties were incorporated to improve the accuracy of the model. By using elasto-thermo-plastic material models, it was determined that the cladding material (Al6061-O) is subjected to tensile stresses that exceed its proportional limits. The fuel foil is subject to compressive stresses and remains below yield. The residual stresses in the plates are significant, and therefore, should not be neglected. In particular, the simulations indicate the presence of high stress gradients at the fuel/cladding interface, thus emphasizing the need for a high quality bond.

  8. 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…

  9. Likert Response Alternative Direction: SA to SD or SD to SA: Does It Make a Difference?

    ERIC Educational Resources Information Center

    Barnette, J. Jackson

    A 20-item survey was designed in 4 forms with response set direction as "strongly disagree" (SD) to "strongly agree" (SA) and SA to SD crossed with the absence or presence of negatively worded item stems. The primary research question related to finding a primacy effect when comparing the two response direction formats. Surveys were administered,…

  10. Studies on the influence of Be content on the corrosion behavior and mechanical properties of Ni-25Cr-10Mo alloys.

    PubMed

    Geis-Gerstorfer, J; Pässler, K

    1993-05-01

    The influence of Be content on the corrosion behavior and strength of dental alloys was examined using experimental Ni-25Cr-10Mo-xBe alloys with graduated Be contents of 0, 0.6, 1.1, 1.6, and 2.1 wt.%. It became evident that the corrosion resistance is reduced even by a 0.6 wt.% Be content. Strength increases by 51% with increasing Be content, while ductility is reduced by 84%. The results revealed that, from the stand-point of corrosion resistance, Be-free Ni-Cr-Mo alloys should be preferred in clinical use.

  11. Neutron diffraction measurement of residual stresses, dislocation density and texture in Zr-bonded U-10Mo “mini” fuel foils and plates

    DOE PAGES

    Brown, Donald William; Okuniewski, Maria A.; Sisneros, Thomas A.; Clausen, Bjorn; Moore, Glenn A.; Balogh, Levente

    2016-09-22

    Here, Al clad U-10Mo fuel plates are being considered for conversion of several research reactors from high-enriched to low-enriched U fuel. Neutron diffraction measurements of the textures, residual phase stresses, and dislocation densities in the individual phases of the mini-foils throughout several processing steps and following hot-isostatic pressing to the Al cladding, have been completed. Recovery and recrystallization of the bare U-10Mo fuel foil, as indicated by the dislocation density and texture, are observed depending on the state of the material prior to annealing and the duration and temperature of the annealing process. In general, the cladding procedure significantly reducesmore » the dislocation density, but the final state of the clad plate, both texture and dislocation density, depends strongly on the final processing step of the fuel foil. In contrast, the residual stress state of the final plate is dominated by the thermal expansion mismatch of the constituent materials.« less

  12. Neutron Diffraction Measurement of Residual Stresses, Dislocation Density and Texture in Zr-bonded U-10Mo ''Mini'' Fuel Foils and Plates

    SciTech Connect

    Brown, Donald W.; Okuniewski, M. A.; Sisneros, Thomas A.; Clausen, Bjorn; Moore, G. A.; Balogh, L

    2014-08-07

    Aluminum clad monolithic uranium 10 weight percent molybdenum (U-10Mo) fuel plates are being considered for conversion of several research and test nuclear reactors from high-enriched to low-enriched uranium fuel due to the inherently high density of fissile material. Comprehensive neutron diffraction measurements of the evolution of the textures, residual phase stresses, and dislocation densities in the individual phases of the mini-foils throughout several processing steps and following hot-isostatic pressing to the Al cladding, have been completed. Recovery and recrystallization of the bare U-10Mo fuel foil, as indicated by the dislocation density and texture, are observed depending on the state of the material prior to annealing and the duration and temperature of the annealing process. In general, the HIP procedure significantly reduces the dislocation density, but the final state of the clad plate, both texture and dislocation density, depends strongly on the final processing step of the fuel foil. In contrast, the residual stresses in the clad fuel plate do not depend strongly on the final processing step of the bare foil prior to HIP bonding. Rather, the residual stresses are dominated by the thermal expansion mismatch of the constituent materials of the fuel plate.

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. 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

  18. Microstructural analysis of a single pass 2.25% Cr-1.0% Mo steel weld metal with different manganese contents

    SciTech Connect

    Guimares de Souza, Luis Felipe; Souza Bott, Ivani de; Ferreira Jorge, Jorge Carlos; Sauer Guimaraes, Ari; Pinheiro Rocha Paranhos, Ronaldo . E-mail: paranhos@uenf.br

    2005-07-15

    Weld metals of the 2.25% Cr-1.0% Mo type with 0.84%, 1.21% and 2.3% Mn produced by submerged-arc welding were analyzed in the as-welded (AW), post weld heat treatment (PWHT) and PWHT followed by step-cooling (SC) heat treatment conditions. Fracture surface analysis revealed an evolution in the mode of fracture due to Mn content variations and heat treatment conditions, the occurrence of intergranular fracture being observed in welds with 2.30% Mn that were step-cooled. Transmission electron microscopy revealed that the microstructure was predominantly composed of bainite, although martensite was also observed for high Mn contents. A marked carbide precipitation was observed, preferentially at grain boundaries. This could be attributed to the SC heat treatment and associated with the embrittlement. However, the application of a de-embrittlement heat treatment to this step cooled weld metal has proved efficient, because the impact energy levels after this heat treatment surpassed those obtained in the stress relieved condition. This indicates that segregation of impurities to grain boundaries was responsible for the low impact energy levels observed after SC of weld metal containing > 0.84% Mn.

  19. 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.

  20. 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.

  1. 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.

  2. On the Components of Segregation Distortion in DROSOPHILA MELANOGASTER. III. Nature of Enhancer of Sd

    PubMed Central

    Brittnacher, John G.; Ganetzky, Barry

    1984-01-01

    Analysis of X-ray-induced deletions in the Segregation Distorter (SD) chromosome, SD-5, revealed that this chromosome had a gene proximal to lt in the centric heterochromatin of 2L that strongly enhanced the meiotic drive caused by the SD chromosome. This Enhancer of Segregation Distortion [E(SD)] locus had not been characterized in earlier studies of SD chromosomes because it cannot be readily separated by recombination from the Responder (Rsp) locus in the proximal heterochromatin of 2R.—To determine whether E(SD) is a general component of all SD chromosomes and to examine further its effects on distortion, we produced deletions of E(SD) in three additional SD chromosomes. Analysis of these deletions leads to the following conclusions: (1) along with Sd and Rsp, E(SD) is common to all SD chromosomes; (2) the E(SD) allele on each SD chromosome enhances distortion by the same amount, which indicates that allelic variation at the E(SD) locus is not responsible for the different drive strengths seen among SD chromosomes; (3) E(SD) causes very little or no distortion by itself in the absence of Sd; (4) E(SD), like Sd, acts in a dosage-dependent manner; (5) E(SD) exerts its effect in cis or trans to Sd; and (6) if E(SD)+ exists, its function is not related to SD. PMID:6428976

  3. 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

  4. 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…

  5. 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.

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

    NASA Astrophysics Data System (ADS)

    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.

  7. 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.

  8. 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

  9. 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...

  10. 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... the Parkston, SD, area, creating controlled airspace at Parkston Municipal Airport (78 FR 25232... ``significant rule'' under DOT Regulatory Policies and Procedures (44 FR 11034; February 26, 1979); and (3)...

  11. 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,...

  12. 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...

  13. 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...

  14. ICHPER-SD Asia Youth Health Related Physical Fitness Test.

    ERIC Educational Resources Information Center

    Journal of the International Council for Health, Physical Education, Recreation, Sport, and Dance, 1994

    1994-01-01

    Presents necessary information for administering the ICHPER-SD Asia Youth Health Related Physical Fitness Test, including descriptions of and scoring for each test item, needed equipment, notes, and suggested preparations for test leaders. The test includes the endurance run, situps in 60 seconds, pullups, sit and reach test, and skinfold…

  15. Insulin resistance in SD rats chronically treated with ethanol

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have previously demonstrated that hepatic insulin signaling is disrupted in Sprague-Dawley (SD) rats fed EtOH-containing diets by total enteral nutrition (TEN). To determine if whole body insulin resistance could be demonstrated in the TEN model, we conducted euglycemic-hyperinsulinemic clamp st...

  16. 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...

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. 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.

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

    PubMed Central

    Powers, P. A.; Ganetzky, B.

    1991-01-01

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

  3. Differential binding of human blood group Sd(a+) and Sd(a-) Tamm-Horsfall glycoproteins with Dolichos biflorus and Vicia villosa-B4 agglutinins.

    PubMed

    Wu, A M; Wu, J H; Watkins, W M; Chen, C P; Song, S C; Chen, Y Y

    1998-06-16

    The binding patterns of human blood group Sd(a+) and Sd(a-) Tamm-Horsfall glycoproteins (THGPs) with respect to four GalNAc specific agglutinins were studied by quantitative precipitin assay (QPA) and enzyme linked lectinosorbent assay (ELLSA). Of the native and asialo Sd(a+) and Sd(a-) THGP tested by QPA and ELLSA, only native and asialo Sd(a+) bound well with Dolichos biflorus (DBA) and Vicia villosa-B4 (VVA-B4), while Sd(a-) THGP reacted poorly with these two lectins. Neither Sd(a+) nor Sd(a-) THGPs reacted with two other GalNAc alpha-anomer specific lectins: Codium fragile subspecies tomentosoides and Artocarpus integrifolia. Furthermore, the binding of asialo Sd(a+)THGP-VVA-B4 and native Sd(a+)THGP-DBA through GalNAc beta--> was confirmed by inhibition assay. These results demonstrate that DBA and VVA-B4 are useful reagents to differentiate between Sd(a+) and Sd(a-) THGP.

  4. 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

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

    PubMed Central

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

    2015-01-01

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

  6. 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.

  7. Learning to eat: birth to age 2 y.

    PubMed

    Birch, Leann L; Doub, Allison E

    2014-03-01

    During the first 2 y of life, development is rapid and includes dramatic changes in eating behavior. Individual patterns of food preferences and eating behaviors emerge and differ depending on the foods offered and on the contexts of feeding during this early period of dietary transition. In this review, we discuss evidence on ways in which early learning influences food preferences and eating behavior, which, in turn, shape differences in dietary patterns, growth, and health. Although the evidence reviewed indicates that this early period of transition provides opportunities to influence children's developing intake patterns, there is no consistent, evidence-based guidance for caregivers who are feeding infants and toddlers; the current Dietary Guidelines are intended to apply to Americans over the age of 2 y. At present, the evidence base with regard to how and what children learn about food and eating behavior during these first years is limited. Before developing guidance for parents and caregivers, more scholarship and research is necessary to understand how infants and toddlers develop the food preferences and self-regulatory processes necessary to promote healthy growth, particularly in today's environment. By the time they reach 2 y of age, children have essentially completed the transition to "table foods" and are consuming diets similar to those of other family members. This article discusses parenting and feeding approaches that may facilitate or impede the development of self-regulation of intake and the acceptance of a variety of foods and flavors necessary for a healthy diet. We review the limited evidence on how traditional feeding practices, familiarization, associative learning, and observational learning affect the development of eating behavior in the context of the current food environment. Areas for future research that could inform the development of anticipatory guidance for parents and caregivers responsible for the care and feeding of young

  8. Biological Parameters and the Segregation Distortion (SD) Phenomenon in DROSOPHILA MELANOGASTER

    PubMed Central

    Trippa, G.; Cicchetti, R.; Loverre, A.; Micheli, A.

    1981-01-01

    The relationship between some biological parameters (mortality, longevity, fertility, fecundity and sex ratio) and segregation of second chromosomes in heterozygous and homozygous SD males has been analyzed. The results obtained in SD/SD+ heterozygous males show: (1) their reduced fertility with respect to that of control males, (2) an alteration in the sex ratio in the SD+ progeny only, and (3) inversely related sex-ratio and segregation distortion values. In SDi/SDj combinations: (1) surprisingly, fertility is intermediate between that of SD/SD+ heterozygous males and that of control males, (2) the segregation ratios of the second chromosomes are normal (0.50), and (3) the sex ratio = 0.50 in both classes of SD progeny. The relationship between mortality (and therefore longevity) and fertility of the different genotypes and fecundity per male indicates that the total productivity of heterozygous males is less than that so far claimed. Indeed, their productivity depends not only on the mechanism of nonformation of the SD+ sperm, but also on their reduced longevity. The k = 0.50 and the high fecundity of SDi/SDj combinations indicate that in these males the SD phenomenon is partially suppressed, the SD chromosomes being insensitive to each other, thus implying that particular Rsp alleles are sensitive to given Sd alleles. The complementation pattern for male fertility of SD homozygous males again supports previous evidence that Sd factors from natural populations are, in effect, different Sd genes. PMID:6795081

  9. Open sd-shell nuclei from first principles

    DOE PAGES

    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

  10. 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.

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

    PubMed Central

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

    2006-01-01

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

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

    PubMed

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

    2006-06-01

    The expression of purinergic P2Y receptors (P2YRs) along the cord, superficial chorionic vessels and cotyledons of the human placenta was analysed and functional assays were performed to determine their vasomotor activity. Immunoblots for the P2Y(1)R and P2Y(2)R revealed a 6- to 8-fold increase in receptor expression from the cord to the chorionic or cotyledon vessels. In the cord and chorionic vessels the receptor distribution was mainly in the smooth muscle, whereas in the cotyledon vessels these receptors were equally distributed between the endothelium and smooth muscle cells. An exception was the P2Y(2)R at the umbilical artery, which was distributed as in the cotyledon. mRNA coding for the P2Y(1)R and P2Y(2)R were detected by RT-PCR and the mRNA coding for the P2Y(4)R, P2Y(6)R and P2Y(11)R was also identified. Application of 2-MeSADP and uridine triphosphate (UTP), preferential P2Y(1)R and P2Y(2)R ligands, respectively, resulted in contraction of isolated rings from umbilical and chorionic vessels. The vasoconstriction was blocked in a concentration-dependent manner by 10-100 nm indomethacin or 10 nm GR32191, suggesting the involvement of thromboxane receptors. MRS 2179, a selective P2Y(1)R antagonist, reduced the 2-MeSADP- but not the UTP-evoked contractions. Perfusion of cotyledons with 2-MeSADP or UTP evoked concentration-dependent reductions in perfusion pressure mediated by the NO-cGMP pathway. Blockade of NO synthase abolished the vasodilatation and the rise in luminal NO elicited by either agonist. MRS 2179 antagonized the dilatation and rise in luminal NO evoked by 2-MeSADP but not by UTP. In summary, P2Y(1)R and P2Y(2)R are unevenly distributed along the human placental vascular tree; both receptors are coupled to different signalling pathways in the cord/chorionic vessels versus the cotyledon leading to opposing vasomotor responses.

  13. 4-Alkyloxyimino Derivatives of Uridine-5′-triphosphate: Distal Modification of Potent Agonists as a Strategy for Molecular Probes of P2Y2, P2Y4, and P2Y6 Receptors

    PubMed Central

    2015-01-01

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

  14. 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

  15. 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.

  16. 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.

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

    PubMed Central

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

    2016-01-01

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

  18. Selective induction of endothelial P2Y6 nucleotide receptor promotes vascular inflammation

    PubMed Central

    Riegel, Ann-Kathrin; Faigle, Marion; Zug, Stephanie; Rosenberger, Peter; Robaye, Bernard; Boeynaems, Jean-Marie

    2011-01-01

    During a systemic inflammatory response endothelial-expressed surface molecules have been strongly implicated in orchestrating immune responses. Previous studies have shown enhanced extracellular nucleotide release during acute inflammatory conditions. Therefore, we hypothesized that endothelial nucleotide receptors could play a role in vascular inflammation. To address this hypothesis, we performed screening experiments and exposed human microvascular endothelia to inflammatory stimuli, followed by measurements of P2Y or P2X transcriptional responses. These studies showed a selective induction of the P2Y6 receptor (> 4-fold at 24 hours). Moreover, studies that used real-time reverse transcription–polymerase chain reaction, Western blot analysis, or immunofluorescence confirmed time- and dose-dependent induction of P2Y6 with tumor necrosis factor α or Lipopolysaccharide (LPS) stimulation in vitro and in vivo. Studies that used MRS 2578 as P2Y6 receptor antagonist showed attenuated nuclear factor κB reporter activity and proinflammatory gene expression in human microvascular endothelial cells in vitro. Moreover, pharmacologic or genetic in vivo studies showed attenuated inflammatory responses in P2Y6−/− mice or after P2Y6 antagonist treatment during LPS-induced vascular inflammation. These studies show an important contribution of P2Y6 signaling in enhancing vascular inflammation during systemic LPS challenge and implicate the P2Y6 receptor as a therapeutic target during systemic inflammatory responses. PMID:21173118

  19. 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

  20. Response Switching Process in Children with Attention-Deficit-Hyperactivity Disorder on the Novel Continuous Performance Test

    ERIC Educational Resources Information Center

    Inoue, Yuki; Inagaki, Masumi; Gunji, Atsuko; Furushima, Wakana; Kaga, Makiko

    2008-01-01

    We examined the effects of previous trials on subsequent trials on performance in the continuous performance test (CPT) in children with attention-deficit-hyperactivity disorder (ADHD). Thirty-five non-medicated children with ADHD (31 males, four females; mean age 9y 10mo [SD 2y 4mo]) and 33 comparison children (20 males, 13 females; mean age 10y…

  1. 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.

  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. 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

  4. Occurrence of Spontaneous Tumors in the Central Nervous System (CNS) of F344 and SD Rats

    PubMed Central

    Nagatani, Mariko; Kudo, Kayoko; Yamakawa, Seiki; Ohira, Toko; Yamaguchi, Yuko; Ikezaki, Shinichiro; Suzuki, Isamu; Saito, Tsubasa; Hoshiya, Toru; Tamura, Kazutoshi; Uchida, Kazuyuki

    2013-01-01

    In order to accurately assess the carcinogenicity of chemicals with regard to rare tumors such as rat CNS tumors, sufficient information about spontaneous tumors are very important. This paper presents the data on the type, incidence and detected age of CNS tumors in F344/DuCrlCrlj (a total of 1363 males and 1363 females) and Crl:CD(SD) rats (a total of 1650 males and 1705 females) collected from in-house background data-collection studies and control groups of carcinogenicity studies at our laboratory, together with those previously reported in F344 and SD rats. The present data on F344/DuCrlCrlj rats (F344 rats) and Crl:CD(SD) rats (SD rats) clarified the following. (1) The incidences of all CNS tumors observed in F344 rats were less than 1%. (2) The incidences of malignant astrocytoma and granular cell tumor were higher in male SD rats than in female SD rats. (3) The incidences of astrocytoma and granular cell tumor were higher in SD rats than in F344 rats. (4) Among astrocytoma, oligodendroglioma and granular cell tumor, oligodendroglioma was detected at the youngest age, followed by astrocytoma, and ultimately, granular cell tumor developed in both strains. The incidences observed in our study were almost consistent with those previously reported in F344 and SD rats. PMID:24155559

  5. 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.

  6. 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

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

    PubMed Central

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

    2016-01-01

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

  8. Discovery of 2-(phenoxypyridine)-3-phenylureas as small molecule P2Y1 antagonists.

    PubMed

    Chao, Hannguang; Turdi, Huji; Herpin, Timothy F; Roberge, Jacques Y; Liu, Yalei; Schnur, Dora M; Poss, Michael A; Rehfuss, Robert; Hua, Ji; Wu, Qimin; Price, Laura A; Abell, Lynn M; Schumacher, William A; Bostwick, Jeffrey S; Steinbacher, Thomas E; Stewart, Anne B; Ogletree, Martin L; Huang, Christine S; Chang, Ming; Cacace, Angela M; Arcuri, Maredith J; Celani, Deborah; Wexler, Ruth R; Lawrence, R Michael

    2013-02-28

    Two distinct G protein-coupled purinergic receptors, P2Y1 and P2Y12, mediate ADP-driven platelet activation. The clinical effectiveness of P2Y12 blockade is well established. Recent preclinical data suggest that P2Y1 and P2Y12 inhibition provide equivalent antithrombotic efficacy, while targeting P2Y1 has the potential for reduced bleeding liability. In this account, the discovery of a 2-(phenoxypyridine)-3-phenylurea chemotype that inhibited ADP-mediated platelet aggregation in human blood samples is described. Optimization of this series led to the identification of compound 16, 1-(2-(2-tert-butylphenoxy)pyridin-3-yl)-3-4-(trifluoromethoxy)phenylurea, which demonstrated a 68 ± 7% thrombus weight reduction in an established rat arterial thrombosis model (10 mg/kg plus 10 mg/kg/h) while only prolonging cuticle and mesenteric bleeding times by 3.3- and 3.1-fold, respectively, in provoked rat bleeding time models. These results suggest that a P2Y1 antagonist could potentially provide a safe and efficacious antithrombotic profile. PMID:23368907

  9. 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

  10. 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).

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

    SciTech Connect

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

    1997-05-30

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

  12. P2Y receptors of MDCK cells: epithelial cell regulation by extracellular nucleotides.

    PubMed

    Insel, P A; Ostrom, R S; Zambon, A C; Hughes, R J; Balboa, M A; Shehnaz, D; Gregorian, C; Torres, B; Firestein, B L; Xing, M; Post, S R

    2001-04-01

    1. Madin-Darby canine kidney (MDCK) cells, a well- differentiated renal epithelial cell line derived from distal tubule/collecting duct, respond to extracellular nucleotides by altering ion flux and the production of arachidonic acid-derived products, in particular prostaglandin E2 (PGE2). Our work has defined the receptors and signalling events involved in such responses. 2. We have found evidence for expression of at least three P2Y receptor subtypes (P2Y1, P2Y2 and P2Y11) in MDCK-D1 cells, a subclone from parental MDCK. 3. These receptors appear to couple to increases in calcium and protein kinase C activity, probably via a Gq/G11-mediated activation of phospholipase C. 4. In addition, P2Y receptor activation can promote a prominent increase in cAMP. This includes both a P2Y2 receptor-mediated cyclo-oxygenase (COX)-dependent component and another COX-independent component mediated by other P2Y receptors. 5. We have documented that changing media in which cells are grown releases ATP and, in turn, activates P2Y receptors. Such release of ATP contributes in a major way to basal cAMP levels in these cells. 6. The data indicate that MDCK cells are a useful model to define the regulation of epithelial cells by extracellular nucleotides. Of particular note, spontaneous or stretch-induced release of ATP and subsequent activation of one or more P2Y receptors contributes to establishing the basal activity of signalling pathways. PMID:11339212

  13. P2Y receptors of MDCK cells: epithelial cell regulation by extracellular nucleotides.

    PubMed

    Insel, P A; Ostrom, R S; Zambon, A C; Hughes, R J; Balboa, M A; Shehnaz, D; Gregorian, C; Torres, B; Firestein, B L; Xing, M; Post, S R

    2001-04-01

    1. Madin-Darby canine kidney (MDCK) cells, a well- differentiated renal epithelial cell line derived from distal tubule/collecting duct, respond to extracellular nucleotides by altering ion flux and the production of arachidonic acid-derived products, in particular prostaglandin E2 (PGE2). Our work has defined the receptors and signalling events involved in such responses. 2. We have found evidence for expression of at least three P2Y receptor subtypes (P2Y1, P2Y2 and P2Y11) in MDCK-D1 cells, a subclone from parental MDCK. 3. These receptors appear to couple to increases in calcium and protein kinase C activity, probably via a Gq/G11-mediated activation of phospholipase C. 4. In addition, P2Y receptor activation can promote a prominent increase in cAMP. This includes both a P2Y2 receptor-mediated cyclo-oxygenase (COX)-dependent component and another COX-independent component mediated by other P2Y receptors. 5. We have documented that changing media in which cells are grown releases ATP and, in turn, activates P2Y receptors. Such release of ATP contributes in a major way to basal cAMP levels in these cells. 6. The data indicate that MDCK cells are a useful model to define the regulation of epithelial cells by extracellular nucleotides. Of particular note, spontaneous or stretch-induced release of ATP and subsequent activation of one or more P2Y receptors contributes to establishing the basal activity of signalling pathways.

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

    PubMed

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

    2013-06-01

    Preclinical data suggests that P2Y1 antagonists, such as diarylurea compound 1, may provide antithrombotic efficacy similar to P2Y12 antagonists and may have the potential of providing reduced bleeding liabilities. This manuscript describes a series of diarylureas bearing solublizing amine side chains as potent P2Y1 antagonists. Among them, compounds 2l and 3h had improved aqueous solubility and maintained antiplatelet activity compared with compound 1. Compound 2l was moderately efficacious in both rat and rabbit thrombosis models and had a moderate prolongation of bleeding time in rats similar to that of compound 1. PMID:23602442

  15. Cytogenetic Analysis of an SD Chromosome from a Natural Population of DROSOPHILA MELANOGASTER

    PubMed Central

    Trippa, G.; Loverre, A.; Cicchetti, R.

    1980-01-01

    The discovery and the cytogenetic characterization of a new SD (Segregation Distorter) chromosome 2 from a natural population in Ranna (Sicily, Italy), SDRa, are reported. The main features of this chromosome are as follows: (a) it contains an SdRa gene with a moderate degree of segregation distortion (k = 0.72), (b) a recessive female sterile gene, fs(2)TLM, responsible for modifications of the morphology and structure of the tests and ovaries is located at 89.7, (c) SDRa/SDRa males and females are viable but sterile, the females due to homozygosis of fs(2)TLM and the males because of homozygosis of a region containing the Sd locus, and (d) SDi/SDj combinations are fertile, thus suggesting that the different Sd factors found in natural populations constitute a multiple allelic series.—These data may indicate that each population containing SD chromosomes has evolved its own genetic architecture for the complex SD system, with specific modifiers and perhaps different Sd genes. The possibility of reconstructing the evolutionary pattern of the SDRa chromosome in the natural Ranna population after the model of Charlesworth and Hartl (1978) and Crow (1979) is considered. PMID:17249043

  16. Chemotherapy-induced uridine diphosphate release promotes breast cancer metastasis through P2Y6 activation

    PubMed Central

    Ma, Xiaobin; Pan, Xinhua; Wei, Yinglei; Tan, Binhe; Yang, Linli; Ren, Hua; Qian, Min; Du, Bing

    2016-01-01

    Although purinergic signaling is important in regulation of immune responses, the therapeutic potential of it in the tumor microenvironment is little defined. In this study, we demonstrate that UDP/P2Y6 signaling facilitates breast cancer metastasis both in vitro and in vivo. We found that P2Y6 is not only aberrantly expressed and mutated in most tumor types, but also highly correlated with poor prognosis in breast cancer patients. Furthermore, the migration and invasion of breast cancer cells was obviously increased by UDP and blocked by P2Y6 specific inhibitor MRS2578 and P2Y6 shRNA. Similar results was also found in breast cancer cell metastasis mouse model. Interestingly, the endogenous agonist UDP was released significantly by doxorubicin treated cells. In addition, the expression and enzyme activity of MMP-9 were both promoted by UDP and inhibited by MRS2578 or P2Y6 shRNA. Furthermore, UDP-induced cell invasion was blocked by an MMP-9 inhibitor. Mechanistically, the MAPKs and NF-κB signaling pathways, known to be involved in regulation of MMP-9 expression, were both activated by UDP. Taken together, our study reveals a relationship between extracellular danger signals and breast cancer metastasis, which suggests the potential therapeutic significance of UDP/P2Y6 signaling in cancer therapy. PMID:27074554

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2010-03-01

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

  19. 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

  20. P2Y2 receptor activation regulates the expression of acetylcholinesterase and acetylcholine receptor genes at vertebrate neuromuscular junctions.

    PubMed

    Tung, Edmund K K; Choi, Roy C Y; Siow, Nina L; Jiang, Joy X S; Ling, Karen K Y; Simon, Joseph; Barnard, Eric A; Tsim, Karl W K

    2004-10-01

    At the vertebrate neuromuscular junction (nmj), ATP is known to be coreleased with acetylcholine from the synaptic vesicles. We have previously shown that the P2Y1 receptor is localized at the nmj. Here, we extend the findings to show that another nucleotide receptor, P2Y2, is also localized there and with P2Y1 jointly mediates trophic responses to ATP. The P2Y2 receptor mRNA in rat muscle increased during development and peaked in adulthood. The P2Y2 receptor protein was shown to become restricted to the nmjs during embryonic development, in chick and in rat. In both rat and chick myotubes, P2Y1 and P2Y2 are expressed, increasing with differentiation, but P2Y4 is absent. The P2Y2 agonist UTP stimulated there inositol trisphosphate production and phosphorylation of extracellular signal-regulated kinases, in a dose-dependent manner. These UTP-induced responses were insensitive to the P2Y1-specific antagonist MRS 2179 (2'-deoxy-N6-methyl adenosine 3',5'-diphosphate diammonium salt). In differentiated myotubes, P2Y2 activation induced expression of acetylcholinesterase (AChE) protein (but not control alpha-tubulin). This was shown to arise from AChE promoter activation, mediated by activation of the transcription factor Elk-1. Two Elk-1-responsive elements, located in intron-1 of the AChE promoter, were found by mutation to act in this gene activation initiated at the P2Y2 receptor and also in that initiated at the P2Y1 receptor. Furthermore, the promoters of different acetylcholine receptor subunits were also stimulated by application of UTP to myotubes. These results indicate that ATP regulates postsynaptic gene expressions via a common pathway triggered by the activation of P2Y1 and P2Y2 receptors at the nmjs. PMID:15258260

  1. 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.

  2. Evaluation of CYP2C19, P2Y12, and ABCB1 polymorphisms and phenotypic response to clopidogrel in healthy Indian adults

    PubMed Central

    Sridharan, Kannan; Kataria, Rachna; Tolani, Drishti; Bendkhale, Shital; Gogtay, Nithya J.; Thatte, Urmila M.

    2016-01-01

    Introduction: CYP2C19 and P2Y12 polymorphisms have been claimed to alter the pharmacodynamic response to clopidogrel. ABCB1 polymorphism has been associated with the efflux of clopidogrel resulting in decreased bioavailability. Due to paucity of data from Indian population, the present study was undertaken to evaluate the association of genetic polymorphisms of CYP2C19, P2Y12, and ABCB1 with inhibition of platelet aggregation (IPA) by clopidogrel. Methods: Healthy adults (n = 90) of either gender were administered single dose of 300 mg clopidogrel. Baseline, 4 h postdose, and day 7 assessment of platelet aggregation and genotype of CYP2C19, P2Y12, and ABCB1 were carried out using standardized laboratory methods. The difference in the maximum platelet aggregation (MPA) between baseline and 4 h postdose was considered as delta-MPA (DMPA), and percentage change of MPA at 4 h from baseline was considered as IPA. Those with an IPA of <30% were considered as poor responders. Inferential statistics was applied to find out significant difference of these parameters between various groups of genetic polymorphisms. Results: Mean (standard deviation [SD]) of MPA (%) at baseline, 4 h postdose, and day 7 were 78 (5), 56 (16), and 71 (8), respectively. Similarly, mean (SD) of DMPA (%) and IPA (%) were 23 (17) and 29 (21), respectively. A total of 54/90 (60%) cases were found to be poor responders to clopidogrel. A wild genotype (*1/*1) of CYP2C19 was observed in 35 (40.2%), 42 (48.3%) had *1/*2, 2 (2.3%) individuals had *1/*3, and 8 (9.2%) had *2/*2 mutant genotypes. Although statistically not significant (P = 0.09), a trend was observed in having decreased inhibition values (both MPA and IPA) as we proceed from wild genotype (*1/*1) to mutant genotypes in the order of *1/*2, *1/*3, and *2/*2. Similarly, in P2Y12, a wild haplotype (H1/H1) was present in 77 (89.5%) and 9 (10.5%) individuals had H1/H2 type. A statistically significant difference in DMPA and IPA was observed with

  3. 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.

  4. 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.

  5. Synthesis and size characterization of silica nanospheres using sedimentation field-flow fractionation (SdFFF).

    PubMed

    Kim, Woon Jung; Ahn, Se Young; Kim, Jai Hoon; Chun, Jong Han; Yu, Jong Shin; Jung, Euo Chang; Lee, Seungho

    2012-01-01

    Silica nanoparticles were synthesized by a conventional emulsion polymerization by mixing ethanol, ammonium hydroxide, water and tetra ethyl orthosilicate (TEOS). A new reaction apparatus was assembled for a large scale synthesis of silica nanospheres in the laboratory, which was designed for uniform mixing of the reactants. The apparatus was equipped with a disc type agitator with six rectangular propellers. The new apparatus allowed high reproducibility in terms of the mean size and the size distribution of the silica nanoparticles with the relative standard deviation of less than about 6%. Sedimentation field-flow fractionation (SdFFF) was employed for determination of the size distribution of the silica nanoparticles. SdFFF provided size-based separation of the silica nanoparticles, with the retention time increasing with the size. When SdFFF analysis was repeated three times for the same sample, the standard deviation was less than 4%, showing reliability of SdFFF in size measurement. SdFFF seems to provide more accurate size distribution than DLS, particularly for those having broad and multimodal size distributions. Change in the agitation speed resulted in significant change in the mean diameter of the silica nanoparticles. Agitation speed of 400 rpm in 3 L reaction vessel yielded silica particles of about 100 nm in diameter, while at 200 rpm in 1 L vessel yielded those of about 500 nm. PMID:22524028

  6. Racial Differences in Resistance to P2Y12 Receptor Antagonists in Type 2 Diabetic Subjects

    PubMed Central

    Duvernay, Matthew T.; Holinstat, Michael; Colowick, Nancy E.; Hudson, Willie J.; Song, Yanna; Harrell, Frank E.

    2014-01-01

    Although resistance to the P2Y12 antagonist clopidogrel is linked to altered drug metabolism, some studies suggest that these pharmacokinetic abnormalities only partially account for drug resistance. To circumvent pharmacokinetic complications and target P2Y12 receptor function we applied the direct P2Y12 antagonist 2-methylthio-AMP (2-methylthioadenosine 5′-monophosphate triethylammonium salt) to purified platelets ex vivo. Platelets were purified from healthy and type 2 diabetes mellitus (T2DM) patients and stimulated with thrombin or the selective protease-activated receptor agonists, protease-activated receptor 1–activating peptide (PAR1-AP), or PAR4-AP. Platelet activation as measured by αIIbβ3 activation, and P-selectin expression was monitored in 141 subjects. Our results demonstrate that, compared with healthy subjects, platelets from diabetic patients are resistant to inhibition by 2-methylthio-AMP, demonstrating P2Y12 pharmacodynamic defects among diabetic patients. Inhibition of thrombin-mediated αIIbβ3 activation by 2-methylthio-AMP was lower in diabetic platelets versus healthy platelets. Subgroup analysis revealed a racial difference in the resistance to 2-methylthio-AMP. We found no resistance in platelets from diabetic African Americans; they were inhibited by 2-methylthio-AMP equally as well as platelets from healthy African Americans. In contrast, platelets from Caucasian patients with diabetes were resistant to P2Y12 antagonism compared with healthy Caucasians. Multivariable analysis demonstrated that other variables, such as obesity, age, or gender, could not account for the differential resistance to 2-methylthio-AMP among races. These results suggest that in addition to altered drug metabolism, P2Y12 receptor function itself is altered in the Caucasian diabetic population. The racial difference in platelet function in T2DM is a novel finding, which may lead to differences in treatment as well as new targets for antiplatelet therapy

  7. The active metabolite of Clopidogrel disrupts P2Y12 receptor oligomers and partitions them out of lipid rafts

    PubMed Central

    Savi, Pierre; Zachayus, Jean-Luc; Delesque-Touchard, Nathalie; Labouret, Catherine; Hervé, Caroline; Uzabiaga, Marie-Françoise; Pereillo, Jean-Marie; Culouscou, Jean-Michel; Bono, Françoise; Ferrara, Pascual; Herbert, Jean-Marc

    2006-01-01

    P2Y12, a G protein-coupled receptor that plays a central role in platelet activation has been recently identified as the receptor targeted by the antithrombotic drug, clopidogrel. In this study, we further deciphered the mechanism of action of clopidogrel and of its active metabolite (Act-Met) on P2Y12 receptors. Using biochemical approaches, we demonstrated the existence of homooligomeric complexes of P2Y12 receptors at the surface of mammalian cells and in freshly isolated platelets. In vitro treatment with Act-Met or in vivo oral administration to rats with clopidogrel induced the breakdown of these oligomers into dimeric and monomeric entities in P2Y12 expressing HEK293 and platelets respectively. In addition, we showed the predominant association of P2Y12 oligomers to cell membrane lipid rafts and the partitioning of P2Y12 out of rafts in response to clopidogrel and Act-Met. The raft-associated P2Y12 oligomers represented the functional form of the receptor, as demonstrated by binding and signal transduction studies. Finally, using a series of receptors individually mutated at each cysteine residue and a chimeric P2Y12/P2Y13 receptor, we pointed out the involvement of cysteine 97 within the first extracellular loop of P2Y12 in the mechanism of action of Act-Met. PMID:16835302

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Zhang, Xu; Lu, Fang; Chen, Yan-Kun; Luo, Gang-Gang; Jiang, Lu-di; Qiao, Lian-Sheng; Zhang, Yan-Ling; Xiang, Yu-Hong

    2016-01-01

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

  11. 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.

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

    PubMed Central

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

    1994-01-01

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

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. Synthesis of ZrO2-Y2O3 "micropowder-nanopowder" compositions

    NASA Astrophysics Data System (ADS)

    Denisova, Elmira I.; Ustyuzhaninova, Irina A.; Kartashov, Vadim V.; Grigorov, Igor G.; Sultanova, Dina T.; Cherepanova, Natalia A.; Mullanurova, Dinara A.; Chernetskiy, Ivan V.; Vlasov, Alexander V.

    2016-09-01

    The conditions for preparing ZrO2-Y2O3 compositions by forming nanostructured powders on micron sized powders of the same composition were investigated. A technique of organic nitrate combustion was used for the synthesis. Fuel reagents were used in the ratio ensuring steady burning flame regime.

  18. Binding of the P2Y2 Nucleotide Receptor to Filamin A Regulates Migration of Vascular Smooth Muscle Cells

    PubMed Central

    Yu, Ningpu; Erb, Laurie; Shivaji, Rikka; Weisman, Gary A.; Seye, Cheikh I.

    2013-01-01

    The functional expression of the G protein– coupled P2Y2 nucleotide receptor (P2Y2R) has been associated with proliferation and migration of vascular smooth muscle cells (SMCs), 2 processes involved in atherosclerosis and restenosis. Activation of the P2Y2R causes dynamic reorganization of the actin cytoskeleton, which transmits biochemical signals and forces necessary for cell locomotion, suggesting that P2Y2Rs may be linked to the actin cytoskeleton. Here, we identified filamin A (FLNa) as a P2Y2R-interacting protein using a yeast 2-hybrid system screen with the C-terminal region of the P2Y2R as bait. The FLNa binding site in the P2Y2R is localized between amino acids 322 and 333. Deletion of this region led to selective loss of FLNa binding to the P2Y2R and abolished Tyr phosphorylation of FLNa induced by the P2Y2R agonist UTP. Using both time-lapse microscopy and the Transwell cell migration assay, we showed that UTP significantly increased SMC spreading on collagen I (6.8 fold; P≤0.01) and migration (3.6 fold; P≤0.01) of aortic SMCs isolated from wild-type mice, as compared with unstimulated SMCs. UTP-induced spreading and migration of aortic SMCs did not occur with cells isolated from P2Y2R knockout mice. Expression of the full-length P2Y2R in SMCs isolated from P2Y2R knockout mice restored both UTP-induced spreading and migration. In contrast, UTP-induced spreading and migration did not occur in SMCs isolated from P2Y2R knockout mice transfected with a mutant P2Y2R that does not bind FLNa. Furthermore, ex vivo studies showed that both ATP and UTP (10 µmol/L) promoted migration of SMCs out of aortic explants isolated from wild-type but not P2Y2R knockout mice. Thus, this study demonstrates that P2Y2R/FLNa interaction selectively regulates spreading and migration of vascular SMCs. PMID:18202316

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

    PubMed Central

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

    2013-01-01

    In utero exposure of the embryo and fetus to radiation has been implicated in malformations or fetal death, and often produces lifelong health consequences such as cancers and mental retardation. Here we demonstrate that deletion of a G-protein-coupled purinergic receptor, P2Y14, confers potent resistance to in utero radiation. Intriguingly, a putative P2Y14 receptor ligand, UDP-glucose, phenocopies the effect of P2Y14 deficiency. These data indicate that P2Y14 is a receptor governing in utero tolerance to genotoxic stress that may be pharmacologically targeted to mitigate radiation toxicity in pregnancy. PMID:23828566

  20. 75 FR 426 - Notice of Application for Disclaimer of Interest, Brookings County, SD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-05

    ... Bureau of Land Management Notice of Application for Disclaimer of Interest, Brookings County, SD AGENCY... Recordable Disclaimer of Interest from the United States for an easement in Brookings County, South Dakota... Recordable Disclaimer of Interest, if issued, will confirm that the United States has no valid interest...

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

    SciTech Connect

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

    2011-05-06

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

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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....

  7. 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... Complex (Complex), which includes Lake Andes NWR, Karl E. Mundt NWR, and Lake Andes Wetland...

  8. 77 FR 65574 - Lake Andes National Wildlife Refuge Complex, Lake Andes, SD; Draft Comprehensive Conservation...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-29

    ... Complex. We started this process through a notice in the Federal Register (72 FR 27328; May, 15, 2007... Fish and Wildlife Service Lake Andes National Wildlife Refuge Complex, Lake Andes, SD; Draft... assessment (EA) for the Lake Andes National Wildlife Refuge Complex (Complex), which includes Lake Andes...

  9. 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.

  10. 78 FR 39310 - Niobrara Confluence and Ponca Bluffs Conservation Areas, NE and SD; Draft Environmental Impact...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-01

    ..., NE and SD; Draft Environmental Impact Statement and Land Protection Plan; Extension of the Public... Bluffs Conservation Areas Draft Environmental Impact Statement and Land Protection Plan until September... Ponca Bluff Conservation Areas. We are extending the public comment period until September 30, 2013....

  11. Differential Susceptibility of SD and CD Rats to a Novel Rat Theilovirus

    PubMed Central

    Drake, Michael T; Riley, Lela K; Livingston, Robert S

    2008-01-01

    Antibodies to rat theilovirus (RTV) have been detected in rats for many years because of their serologic crossreactivity with strains of Theiler murine encephalomyelitis virus (TMEV) of mice. Little information exists regarding this pathogen, yet it is among the most common viruses detected in serologic surveys of rats used in research. In the study reported here, a novel isolate of RTV, designated RTV1, was cultured from the feces of infected rats. The RTV1 genome contained 8094 nucleotides and had approximately 95% identity with another rat theilovirus, NSG910, and 73% identity with TMEV strains. In addition, the genome size of RTV1 was similar to those of TMEV strains but larger than that reported for NSG910. Oral inoculation of Sprague–Dawley (SD) and CD male rats (n = 10 each group) with RTV1 revealed that SD rats were more susceptible than CD rats to RTV1 infection. At 14 d postinoculation, 100% of SD rats shed virus in the feces, and 70% were positive for RTV serum antibodies. By 56 d postinoculation 30% of SD rats continued to have detectable virus in the feces, and 90% had seroconverted. In contrast, in inoculated CD rats RTV was detected only in the feces at 14 d postinoculation, at which time 40% of CD rats were fecal positive. By 56 d postinoculation only 20% of CD rats had detectable RTV serum antibodies. Our data provide additional sequence information regarding a rat-specific Cardiovirus and indicate that SD rats are more susceptible than CD rats to RTV1 infection. PMID:19004372

  12. 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

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

    PubMed

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

    2015-08-01

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

  14. 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

  15. 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

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

    PubMed

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

    2015-10-01

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

  17. 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.

  18. P2y receptor-mediated angiogenesis via vascular endothelial growth factor receptor 2 signaling.

    PubMed

    Rumjahn, Sharif M; Baldwin, Karla A; Buxton, Iain L O

    2007-01-01

    Pathological as well as physiological angiogenesis is known to be regulated by such factors as nucleotides and Vascular Endothelial Growth Factor (VEGF). Activated P2Y nucleotide receptors have been observed to associate and transactivate VEGF Receptor 2 (VEGFR2), suggesting a cooperation between nucleotide and VEGF signaling in angiogenesis. P2YR mediated VEGFR2 signaling therefore may be important in describing the angiogenic signaling of nucleotides such as ATP. Here, we provide evidence that supports the notion of P2YR-VEGFR2 signaling. The significant angiogenic effect of P2Y1/2 receptor agonists (100 microM ATP and 10 microM 2MS-ATP) on endothelial cell tubulogenesis was suppressed back to near control levels upon addition of 1 microM SU1498 (specific VEGFR2 tyrosine kinase inhibitor). We believe that this P2YR-VEFGR2 signaling is an important component of pathological, as well as physiological angiogenesis.

  19. 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.

  20. 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.

  1. FUV Spectroscopy of the sdOB Primary of the Eclipsing Binary System AA Dor

    NASA Astrophysics Data System (ADS)

    Fleig, J.; Rauch, T.; Werner, K.; Kruk, J. W.

    AADor is an eclipsing, close, post common-envelope binary (PCEB). We present a detailed spectral analysis of its sdOB primary based on observations obtained with the Far Ultraviolet Spectroscopic Explorer (FUSE). Due to a strong contamination by interstellar absorption, we had to model both, the stellar spectrum as well as the interstellar line absorption in order to reproduce the FUV observation well and to determine the photospheric parameters precisely.

  2. 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.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  5. Calcium signalling through nucleotide receptor P2Y2 in cultured human vascular endothelium.

    PubMed

    Viana, F; de Smedt, H; Droogmans, G; Nilius, B

    1998-08-01

    Microfluorometric measurements in Fura-2-loaded single cultured human vascular endothelial cells were used to characterize the intracellular calcium [Ca2+]i responses triggered by extracellular application of adenosine 5'-triphosphate (ATP) and other nucleotides. Application of ATP or uridine 5'-triphosphate (UTP) gave rise to dose-dependent elevations of [Ca2+]i in all the cells tested. At saturating concentrations of agonist, the [Ca2+]i response was biphasic, with an early peak and a sustained plateau. Unlike peak responses, the sustained Ca2+ plateau was sensitive to removal of Ca2+ from the external medium. Mn2+ quenching revealed the presence of Ca2+ influx during the agonist-induced calcium plateau. The agonist-evoked calcium plateau was inhibited in a dose-dependent manner by the Cl-channel blocker NPPB, by the divalent cation Ni2+ and by the imidazole antimycotic econazole. Previously, these compounds have been shown to block store-operated Ca2+ entry. The two phases of the agonist-evoked [Ca2+]i response were blocked by the specific phospholipase C inhibitor U-73122 and by intracellular injection of low molecular weight heparin, suggesting the involvement of IP3-sensitive intracellular Ca2+ stores. The pharmacological profile of the response, using different nucleotides and analogues, ATP = UTP > ADP = UDP, and no responses to P2X1 and P2Y1 agonists, suggested the involvement of P2Y2 receptors. The expression of mRNA for the P2Y2 receptor was detected by RT-PCR analysis. These results indicate that P2Y2 receptors linked to intracellular Ca2+ mobilization are present in human vascular endothelial cells. The initial [Ca2+]i mobilization is followed by a phase of elevated [Ca2+]i influx.

  6. 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

  7. 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

  8. 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.

  9. [Inactivation of HIV-1 in human femur heads using a heat disinfection system (Lobator SD-1)].

    PubMed

    von Garrel, T; Knaepler, H; Gürtler, L

    1997-05-01

    The use of allogenic bone transplants in surgery has been greatly diminished owing to the risk of transmitting infectious diseases. This risk can be reduced by the use of a thermal disinfection system (Lobator SD-1). This is achieved by increasing the temperature to 80 degrees C, inactivating a number of bacterial and viral agents. In this study the decay of HIV at high temperature in the Lobator SD-1 was researched. In the center of human femoral heads 100 microliters of a highly concentrated suspension of free and cell-bound HIV (10(10)) was exposed to the thermal process at intervals of 5, 10, 20, 30, 40, 50 and 62 min. For the recultivation HUT-78 cells were used through titration of the virus suspension in ten-fold dilutions over ten dilution steps and incubation up to a maximum of 21 days. Evidence of the virus was checked through observing giant cell formations and quantitative determination of p24 antigen using an Elisa test. Linear virus inactivation was found based upon the time the virus was exposed to heat. After a treatment of 40 min in the disinfection system, total virus inactivation was achieved. The normal disinfection process time using Lobator SD-1 is 92 min. A temperature of 80 degrees C is reached after approximately 45 min. The results prove that this system totally inactivates HIV in human femoral heads.

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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).

  15. 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.

  16. Physical properties of Kx(Ni,Fe)2-ySe2 single crystal alloys1

    NASA Astrophysics Data System (ADS)

    Ryu, Hyejin; Lei, Hechang; Wang, Kefeng; Graf, D.; Bozin, Emil S.; Warren, J. B.; Petrovic, C.

    2013-03-01

    We report physical properties and ground state phase diagram of Kx(Fe,Ni)2-ySe2 single crystal alloy series. The ground state evolves from a heavy-Fermion-like metal KxNi2-ySe2 (I4/mmm) to a phase separated superconducting KxFe2-ySe2 (I4/m and I4/mmm space groups). Intermediate alloys show rich variety of ground states including semiconducting magnetic spin glass as Ni is replaced by Fe. We will address magnetic, thermodynamic, electronic and thermal transport properties and their connection to relevant structural parameters. 1Work at Brookhaven is supported by the U.S. DOE under Contract No. DE-AC02-98CH10886 and in part by the Center for Emergent Superconductivity, an Energy Frontier Research Center funded by the U.S. DOE, Office for Basic Energy Science (H. L. and C. P). Work at the National High Magnetic Field Laboratory is supported by the DOE NNSA DEFG52-10NA29659 (D.G.), by the NSF Cooperative Agreement No. DMR-0654118, and by the state of Florida.

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

    SciTech Connect

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

    1996-09-01

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

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

    PubMed

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

    2012-01-01

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

  19. 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

  20. 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

  1. 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

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

    PubMed Central

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

    2014-01-01

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

  3. P2Y1 receptor inhibits GABA transport through a calcium signalling-dependent mechanism in rat cortical astrocytes.

    PubMed

    Jacob, Pedro F; Vaz, Sandra H; Ribeiro, Joaquim A; Sebastião, Ana M

    2014-08-01

    Astrocytes express a variety of purinergic (P2) receptors, involved in astrocytic communication through fast increases in [Ca(2+) ]i . Of these, the metabotropic ATP receptors (P2Y) regulate cytoplasmic Ca(2+) levels through the PLC-PKC pathway. GABA transporters are a substrate for a number of Ca(2+) -related kinases, raising the possibility that calcium signalling in astrocytes impact the control of extracellular levels of the major inhibitory transmitter in the brain. To access this possibility we tested the influence of P2Y receptors upon GABA transport into astrocytes. Mature primary cortical astroglial-enriched cultures expressed functional P2Y receptors, as evaluated through Ca(2+) imaging, being P2Y1 the predominant P2Y receptor subtype. ATP (100 μM, for 1 min) caused an inhibition of GABA transport through either GAT-1 or GAT-3 transporters, decreasing the Vmax kinetic constant. ATP-induced inhibition of GATs activity was still evident in the presence of adenosine deaminase, precluding an adenosine-mediated effect. This, was mimicked by a specific agonist for the P2Y1,12,13 receptor (2-MeSADP). The effect of 2-MeSADP on GABA transport was blocked by the P2 (PPADS) and P2Y1 selective (MRS2179) receptor antagonists, as well as by the PLC inhibitor (U73122). 2-MeSADP failed to inhibit GABA transport in astrocytes where intracellular calcium had been chelated (BAPTA-AM) or where calcium stores were depleted (α-cyclopiazonic acid, CPA). In conclusion, P2Y1 receptors in astrocytes inhibit GABA transport through a mechanism dependent of P2Y1 -mediated calcium signalling, suggesting that astrocytic calcium signalling, which occurs as a consequence of neuronal firing, may operate a negative feedback loop to enhance extracellular levels of GABA. PMID:24733747

  4. The physical association of the P2Y12 receptor with PAR4 regulates arrestin-mediated Akt activation.

    PubMed

    Khan, Aasma; Li, Dongjun; Ibrahim, Salam; Smyth, Emer; Woulfe, Donna S

    2014-07-01

    It is now well accepted that protease activated receptor (PAR) 1 and PAR4 have differential roles in platelet activation. PAR4, a low-affinity thrombin receptor in human platelets, participates in sustained platelet activation in a P2Y12-dependent manner; however, the mechanisms are not defined. Our previous studies demonstrated that thrombin induces the association of PAR4 with P2Y12, together with arrestin recruitment to the complex. Here we show that PAR4 and P2Y12 directly interact to coregulate Akt signaling after PAR4 activation. We observed direct and specific interaction of P2Y12 with PAR4 but not PAR1 by bioluminescent resonance energy transfer when the receptors were coexpressed in human embryonic kidney 293T cells. PAR4-P2Y12 dimerization was promoted by PAR4-AP and inhibited by P2Y12 antagonist. By using sequence comparison of the transmembrane domains of PAR1 and PAR4, we designed a mutant form of PAR4, "PAR4SFT," by replacing LGL194-196 at the base of transmembrane domain 4 with the corresponding aligned PAR1 residues SFT 220-222. PAR4SFT supported only 8.74% of PAR4-P2Y12 interaction, abolishing P2Y12-dependent arrestin recruitment to PAR4 and Akt activation. Nonetheless, PAR4SFT still supported homodimerization with PAR4. PAR4SFT failed to induce a calcium flux when expressed independently; however, coexpression of increasing concentrations of PAR4SFT, together with PAR4 potentiated PAR4-mediated calcium flux, suggested that PAR4 act as homodimers to signal to Gq-coupled calcium responses. In conclusion, PAR4 LGL (194-196) governs agonist-dependent association of PAR4 with P2Y12 and contributes to Gq-coupled calcium responses. PAR4-P2Y12 association supports arrestin-mediated sustained signaling to Akt. Hence, PAR4-P2Y12 dimerization is likely to be important for the PAR4-P2Y12 dependent stabilization of platelet thrombi.

  5. The physical association of the P2Y12 receptor with PAR4 regulates arrestin-mediated Akt activation.

    PubMed

    Khan, Aasma; Li, Dongjun; Ibrahim, Salam; Smyth, Emer; Woulfe, Donna S

    2014-07-01

    It is now well accepted that protease activated receptor (PAR) 1 and PAR4 have differential roles in platelet activation. PAR4, a low-affinity thrombin receptor in human platelets, participates in sustained platelet activation in a P2Y12-dependent manner; however, the mechanisms are not defined. Our previous studies demonstrated that thrombin induces the association of PAR4 with P2Y12, together with arrestin recruitment to the complex. Here we show that PAR4 and P2Y12 directly interact to coregulate Akt signaling after PAR4 activation. We observed direct and specific interaction of P2Y12 with PAR4 but not PAR1 by bioluminescent resonance energy transfer when the receptors were coexpressed in human embryonic kidney 293T cells. PAR4-P2Y12 dimerization was promoted by PAR4-AP and inhibited by P2Y12 antagonist. By using sequence comparison of the transmembrane domains of PAR1 and PAR4, we designed a mutant form of PAR4, "PAR4SFT," by replacing LGL194-196 at the base of transmembrane domain 4 with the corresponding aligned PAR1 residues SFT 220-222. PAR4SFT supported only 8.74% of PAR4-P2Y12 interaction, abolishing P2Y12-dependent arrestin recruitment to PAR4 and Akt activation. Nonetheless, PAR4SFT still supported homodimerization with PAR4. PAR4SFT failed to induce a calcium flux when expressed independently; however, coexpression of increasing concentrations of PAR4SFT, together with PAR4 potentiated PAR4-mediated calcium flux, suggested that PAR4 act as homodimers to signal to Gq-coupled calcium responses. In conclusion, PAR4 LGL (194-196) governs agonist-dependent association of PAR4 with P2Y12 and contributes to Gq-coupled calcium responses. PAR4-P2Y12 association supports arrestin-mediated sustained signaling to Akt. Hence, PAR4-P2Y12 dimerization is likely to be important for the PAR4-P2Y12 dependent stabilization of platelet thrombi. PMID:24723492

  6. 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.

  7. 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

  8. 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.

  9. Sex differences in the behavioral response to methylphenidate in three adolescent rat strains (WKY, SHR, SD).

    PubMed

    Chelaru, Mircea I; Yang, Pamela B; Dafny, Nachum

    2012-01-01

    Methylphenidate (MPD) is the most widely used drug in the treatment of attention-deficit hyperactivity disorder (ADHD). ADHD has a high incidence in children and can persist in adolescence and adulthood. The relation between sex and the effects of acute and chronic MPD treatment was examined using adolescent male and female rats from three genetically different strains: spontaneously hyperactive rat (SHR), Wistar-Kyoto (WKY) and Sprague-Dawley (SD). Rats from each strain and sex were randomly divided into a control group that received saline injections and three MPD groups that received either 0.6 or 2.5 or 10mg/kg MPD injections. All rats received saline on experimental day 1 (ED1). On ED2 to ED7 and ED11, the rats were injected either with saline or MPD and received no treatment on ED8-ED10. The open field assay was used to assess the dose-response of acute and chronic MPD administration. Significant sex differences were found. Female SHR and SD rats were significantly more active after MPD injections than their male counterparts, while the female WKY rats were less active than the male WKY rats. Dose dependent behavioral sensitization or tolerance to MPD treatment was not observed for SHR or SD rats, but tolerance to MPD was found in WKY rats for the 10mg/kg MPD dose. The use of dose-response protocol and evaluating different locomotor indices provides the means to identify differences between the sexes and the genetic strain in adolescent rats. In addition these differences suggest that the differences to MPD treatment between the sexes are not due to the reproductive hormones.

  10. 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.

  11. Attenuation of lithium-induced natriuresis and kaliuresis in P2Y2 receptor knockout mice

    PubMed Central

    Zhang, Yue; Li, Lijun; Kohan, Donald E.; Ecelbarger, Carolyn M.

    2013-01-01

    Whole body knockout (KO) of the P2Y2 receptor (P2Y2R) results in enhanced vasopressin V2 receptor activity and increased renal Na+ conservation. We hypothesized that P2Y2R KO mice would be less sensitive to lithium-induced natriuresis and kaliuresis due to attenuated downregulation of one or more of the major renal Na+ or K+ transporter/channel proteins. KO and wild-type (WT) mice were fed a control or lithium-added diet (40 mmol/kg food) for 14 days. Lithium-induced natriuresis and kaliuresis were significantly (∼25%) attenuated in KO mice. The subunits of the epithelial Na+ channel (ENaC) were variably affected by lithium and genotype, but, overall, medullary levels were decreased substantially by lithium (15–60%) in both genotypes. In contrast, cortical, β-, and γ-ENaC were increased by lithium (∼50%), but only in WT mice. Moreover, an assessment of ENaC activity by benzamil sensitivity suggested that lithium increased ENaC activity in WT mice but in not KO mice. In contrast, medullary levels of Na+-K+-2Cl− cotransporter 2 and cortical levels of the renal outer medullary K+ channel were not downregulated by lithium and were significantly (15–76%) higher in KO mice under both dietary conditions. In addition, under control conditions, tissue osmolality of the inner medulla as well as furosemide sensitivity were significantly higher in KO mice versus WT mice. Therefore, we suggest that increased expression of these proteins, particularly in the control state, reduces Na+ delivery to the distal nephron and provides a buffer to attenuate collecting duct-mediated natriuresis and kaliuresis. Additional studies are warranted to explore the potential therapeutic benefits of purinergic antagonism. PMID:23739592

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

    NASA Astrophysics Data System (ADS)

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

    2016-11-01

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

  13. EPR of Gd3+ ion in mixed CeO2-Y2O3 nanocrystals

    NASA Astrophysics Data System (ADS)

    Aminov, L. K.; Kurkin, I. N.; Rakhmatullin, R. M.; Böttcher, R.; Pöppl, A.; Sen, S.

    2009-11-01

    This paper reports on the results of EPR studies of mixed CeO2-Y2O3 crystals (including nanosized crystals) doped by gadolinium ions. It is revealed that the width of the line corresponding to the allowed transition 1/2 ↔ -1/2 between the Kramers-conjugated states |±1/2> of the Gd3+ ion decreases with a decrease in the powder size from macrosizes to nanosizes. The observed dependence can be due to the increase in the unit cell size during grinding of the samples.

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

    DOE PAGES

    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”).

  15. 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.

  16. 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

  17. Microscopic spin dephasing and magnetization relaxation in an s-d model

    NASA Astrophysics Data System (ADS)

    Schneider, Hans Christian; Baral, Alexander

    2014-03-01

    We calculate the spin dynamics in a model of itinerant carriers coupled antiferromagnetically to a macrospin (''s-d model''). The dephasing comes in via the coupling to a phonon bath in the presence of spin-orbit coupling, which we take to be of the Bychkov-Rashba type. Using a mean-field approximation for the s-d model with an antiferromagnetic exchange coupling, we derive Boltzmann scattering integrals for itinerant-carrier spin density matrix, i.e., for the distributions and spin coherences. The spin density matrix is needed because of a constant change of the longitudinal and transverse directions during the coupled dynamics of the itinerant spins and the macrospin. Due to the Rashba spin-orbit coupling, the resulting model describes a form of Elliot-Yafet type carrier-spin relaxation due to electron-phonon scattering within an equation-of-motion formalism. We extrapolate dephasing- and magnetization times T1 and T2 and draw a comparison to phenomenological equations such as the Landau-Lifshitz or Landau-Lifshitz Gilbert equations. We then analyze the magnetization precession and relaxation of the coupled carrier spins and macrospin in an anisotropy field, and find a carrier mediated dephasing of the macrospin via mean-field

  18. 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).

  19. Narrowing of the neutron sd- pf shell gap in 29Na

    NASA Astrophysics Data System (ADS)

    Hurst, A. M.; Wu, C. Y.; Becker, J. A.; Stoyer, M. A.; Pearson, C. J.; Hackman, G.; Schumaker, M. A.; Svensson, C. E.; Austin, R. A. E.; Ball, G. C.; Bandyopadhyay, D.; Barton, C. J.; Boston, A. J.; Boston, H. C.; Churchman, R.; Cline, D.; Colosimo, S. J.; Cross, D. S.; Demand, G.; Djongolov, M.; Drake, T. E.; Garrett, P. E.; Gray-Jones, C.; Green, K. L.; Grint, A. N.; Hayes, A. B.; Leach, K. G.; Kulp, W. D.; Lee, G.; Lloyd, S.; Maharaj, R.; Martin, J.-P.; Millar, B. A.; Mythili, S.; Nelson, L.; Nolan, P. J.; Oxley, D. C.; Padilla-Rodal, E.; Phillips, A. A.; Porter-Peden, M.; Rigby, S. V.; Sarazin, F.; Sumithrarachchi, C. S.; Triambak, S.; Walker, P. M.; Williams, S. J.; Wong, J.; Wood, J. L.

    2009-04-01

    The wave-function composition for the low-lying states in 29Na was explored by measuring their electromagnetic properties using the Coulomb-excitation technique. A beam of 29Na ions, postaccelerated to 70 MeV, bombarded a 110Pd target with a rate of up to 600 particles per second at the recently commissioned ISAC-II facility at TRIUMF. Six segmented HPGe clover detectors of the TIGRESS γ-ray spectrometer were used to detect deexcitation γ rays in coincidence with scattered or recoiling charged particles in the segmented silicon detector, BAMBINO. The reduced transition matrix element | <5/2 1 + | | E 2 | |3/2 gs + > | in 29Na was derived to be 0.237(21) e b from the measured γ-ray yields for both projectile and target. This first-time measured value is consistent with the most recent Monte Carlo shell-model calculation, indicating a significant admixture of both sd and pf components in the wave function, and also providing evidence for the narrowing of the neutron sd- pf shell gap from ∼ 6 MeV for stable nuclei to ∼ 3 MeV for 29Na.

  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.

  1. 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.

  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. 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.

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

    PubMed

    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

    2014-10-01

    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 (0.3mg/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.

  5. 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

  6. P2Y2 nucleotide receptor activation enhances the aggregation and self-organization of dispersed salivary epithelial cells.

    PubMed

    El-Sayed, Farid G; Camden, Jean M; Woods, Lucas T; Khalafalla, Mahmoud G; Petris, Michael J; Erb, Laurie; Weisman, Gary A

    2014-07-01

    Hyposalivation resulting from salivary gland dysfunction leads to poor oral health and greatly reduces the quality of life of patients. Current treatments for hyposalivation are limited. However, regenerative medicine to replace dysfunctional salivary glands represents a revolutionary approach. The ability of dispersed salivary epithelial cells or salivary gland-derived progenitor cells to self-organize into acinar-like spheres or branching structures that mimic the native tissue holds promise for cell-based reconstitution of a functional salivary gland. However, the mechanisms involved in salivary epithelial cell aggregation and tissue reconstitution are not fully understood. This study investigated the role of the P2Y2 nucleotide receptor (P2Y2R), a G protein-coupled receptor that is upregulated following salivary gland damage and disease, in salivary gland reconstitution. In vitro results with the rat parotid acinar Par-C10 cell line indicate that P2Y2R activation with the selective agonist UTP enhances the self-organization of dispersed salivary epithelial cells into acinar-like spheres. Other results indicate that the P2Y2R-mediated response is dependent on epidermal growth factor receptor activation via the metalloproteases ADAM10/ADAM17 or the α5β1 integrin/Cdc42 signaling pathway, which leads to activation of the MAPKs JNK and ERK1/2. Ex vivo data using primary submandibular gland cells from wild-type and P2Y2R(-/-) mice confirmed that UTP-induced migratory responses required for acinar cell self-organization are mediated by the P2Y2R. Overall, this study suggests that the P2Y2R is a promising target for salivary gland reconstitution and identifies the involvement of two novel components of the P2Y2R signaling cascade in salivary epithelial cells, the α5β1 integrin and the Rho GTPase Cdc42.

  7. Purinergic signaling via P2Y receptors up-mediates IL-6 production by liver macrophages/Kupffer cells.

    PubMed

    Ishimaru, Makiko; Yusuke, Negishi; Tsukimoto, Mitsutoshi; Harada, Hitoshi; Takenouchi, Takato; Kitani, Hiroshi; Kojima, Shuji

    2014-06-01

    Resident macrophages in the liver (Kupffer cells) produce various cytokines and chemokines, and have important roles in hepatitis and liver fibrosis. The cells are activated by various factors, for example lipopolysaccharide (LPS), which is an endotoxin and is high in the blood of patients with liver cirrhosis. Involvement of P2 receptors in the release of pro-inflammatory cytokines from Kupffer cells is little. In this study, we investigated purinergic signaling in the release of pro-inflammatory cytokines, such as IL-6 and TNF-α, from liver Kupffer cells of C57BL/6 mice (KUP5 cells). KUP5cells were isolated from C57BL/6 mice and cultivated with Dulbecco's modified Eagle's medium. The cells were stimulated with LPS. LPS-induced IL-6 production by KUP5 cells was suppressed significantly by pretreatments with non-selective P2 antagonist suramin, P2Y13antagonist MRS2211, and ecto-nucleotidase, whereas P2Y receptor agonists, significantly increased the IL-6 production. P2Y13knockdown reduced LPS-induced IL-6 production, but by less than 50%. These results would suggest that P2Y receptors including P2Y13and others, may involves in LPS-induced IL-6 production in Kupffer cells, leading to the liver inflammation. Therefore, we first showed the importance of purinergic signaling via P2Y receptors in the activation of Kupffer cells and liver injury, which is worthwhile in drug development for liver diseases. PMID:24849676

  8. 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

  9. 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

  10. NTPDase2 and the P2Y1 receptor are not required for mammalian eye formation.

    PubMed

    Gampe, Kristine; Haverkamp, Silke; Robson, Simon C; Gachet, Christian; Hüser, Laura; Acker-Palmer, Amparo; Zimmermann, Herbert

    2015-03-01

    Eye formation in vertebrates is controlled by a conserved pattern of molecular networks. Homeobox transcription factors are crucially involved in the establishment and maintenance of the retina. A previous study of Massé et al. (Nature, 449: 1058-62, 2007) using morpholino knockdown identified the ectonucleotidase NTPDase2 and the P2Y1 receptor as essential elements for eye formation in embryos of the clawed frog Xenopus laevis. In order to investigate whether a similarly essential mechanism would be active in mammalian eye development, we analyzed mice KO for Entpd2 or P2ry1 as well as double KO for Entpd2/P2ry1. These mice developed normal eyes. In order to identify potential deficits in the molecular identity or in the arrangement of the cellular elements of the retina, we performed an immunohistological analysis using a variety of retinal markers. The analysis of single and double KO mice demonstrated that NTPDase2 and P2Y1 receptors are not required for murine eye formation, as previously shown for eye development in Xenopus laevis.

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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

  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. P2y Receptor-Mediated Angiogenesis via Vascular Endothelial Growth Factor Receptor 2 Signaling

    PubMed Central

    Rumjahn, Sharif M.; Baldwin, Karla A; Buxton, Iain L. O.

    2011-01-01

    Pathological as well as physiological angiogenesis is known to be regulated by such factors as nucleotides and Vascular Endothelial Growth Factor (VEGF). Activated P2Y nucleotide receptors have been observed to associate and transactivate VEGF Receptor 2 (VEGFR2), suggesting a cooperation between nucleotide and VEGF signaling in angiogenesis. P2YR mediated VEGFR2 signaling therefore may be important in describing the angiogenic signaling of nucleotides such as ATP. Here, we provide evidence that supports the notion of P2YR-VEGFR2 signaling. The significant angiogenic effect of P2Y1/2 receptor agonists (100 μM ATP and 10 μM 2MS-ATP) on endothelial cell tubulogenesis was suppressed back to near control levels upon addition of 1 μM SU1498 (specific VEGFR2 tyrosine kinase inhibitor). We believe that this P2YR-VEFGR2 signaling is an important component of pathological, as well as physiological angiogenesis. PMID:18605230

  18. 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

  19. 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).

  20. 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.

  1. 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.

  2. Rate tables for the weak processes of sd-shell nuclei in stellar matter

    SciTech Connect

    Oda, Takeshi; Hino, Masayuki; Muto, Kazuo ); Takahara, Mariko ); Sato, Katsuhiko )

    1994-03-01

    The weak interaction rates in stellar matter are calculated for the sd-shell nuclei in the full-shell model configurations using the effective interaction of Wildenthal, taking into account the recent extensive compilations of experimental energy levels and Gamow-Teller [beta] decay rates. Based on comparisons between the present calculation and that of Fuller, Fowler, and Newman (FFN), it is pointed out that correct treatment of nuclear structure effects is decisive in attaining reliable weak interaction rates in stellar matter. The weak rates are tabulated at the same grid points of density and temperature as those of FFN, for the ranges 10 [le] pY[sub e] (g[center dot]cm[sup [minus]3]) [le] 10[sup 11] and 0.01 [times] 10[sup 9] [le] T (K) [le] 30 [times] 10[sup 9]. 33 refs., 3 figs., 2 tabs.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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

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

    PubMed

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

    2009-09-01

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

  10. [Bone bank management using a thermal disinfection system (Lobator SD-1). A critical analysis].

    PubMed

    Hofmann, C; von Garrel, T; Gotzen, L

    1996-07-01

    In the study presented on 380 allogenic bone donations from living and organ donors, we analyzed the safety of allograft handling bone-band documentation, logistics and costs. For transplant treatment we routinely used a thermal disinfection system (Lobator SD-1). From 380 allograft donors, 400 bone transplants were gained. The rejection rate was 12.2%. After thermal disinfection for 1 h at 80 degrees C, the grafts were cryopreserved at -80 degrees C and released from the bone bank for potential transplantation after 14-16 days. Five of 730 microbiological specimens showed bacterial contamination after thermal graft decontamination. The bacterial species found on the allografts normally have an inactivation temperature under 80 degrees C. Therefore, only secondary contamination can explain the positive bacteriological test results. With reform of the health care system the economical aspects of bone banking have triggered more interest. The cost for one bone transplant released from the bone bank was 424.75 DM: the overall cost for the bone bank in one year was 75,076 DM. Laboratory (58.2%) and material costs (22.5%) were the major factors. Personnel costs and apparatus costs were relatively low (< 20%). With introduction of the thermal disinfection system (Lobator SD-1) into the bone bank, the safety of allogenic bone transplants was greatly improved. Clinical and serological donor screening must be performed according to international bone bank directives. Considering the low rejection rate and the short turnover rate, the economical costs could be reduced. Using an appropriate disinfection system (thermal disinfection at 80 degrees C), laboratory tests covering venereal diseases, malaria and cytomegalia are no longer required. Also, secondary HIV testing of living donors can be omitted without reducing the safety of the transplant.

  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.

  12. Negative Segregation Distortion in the Sd System of Drosophila Melanogaster: A Challenge to the Concept of Differential Sensitivity of Rsp Alleles

    PubMed Central

    Hiraizumi, Y.

    1990-01-01

    Current models of segregation distortion based on previous experimental results predict that, in the Sd heterozygous Rsp(i)/Rsp(s) male, the chromosome carrying the sensitive Rsp(s) allele is distorted or transmitted in a frequency smaller than that of the expected Mendelian 0.5 relative to the chromosome carrying the insensitive Rsp(i) allele. The present study presents a case where this does not occur, that is, when the genotype of the males is supp-X(SD)/Y; Sd E(SD)Rsp(i) M(SD)(+)/Sd(+) E(SD)(+) Rsp(s) M(SD)(+) where supp-X(SD) is an X chromosome carrying a strong suppressor or suppressors of SD activity and SD(+) E(SD)(+) Rsp(s) M(SD)(+) is the standard cn bw chromosome. Following the ``inseminated female transfer'' procedure, young males of the above genotype carrying the standard-X instead of the supp-X(SD) chromosome show k values for the SD chromosome (frequencies of the SD chromosome recovered among progeny) of about 0.75, but with the supp-X(SD) chromosome, the k values are reduced to 0.36-0.41. Several possibilities other than the mechanism of segregation distortion to explain the reduced k values are ruled out. The occurrence of ``negative segregation distortion'' is clearly demonstrated, where the chromosome carrying the Rsp(i) allele is distorted, but the chromosome with the Rsp(s) allele is not. This result requires a major modification of the current models or even a new model for the mechanism of segregation distortion to accommodate Rsp allele sensitivity or insensitivity. The present study also shows that males of the genotype, Sd Rsp(ss) M(SD)(+)/Sd(+) Rsp(ss) M(SD), are almost completely sterile, but their fertility is considerably increased when SD activity is suppressed by the presence of the supp-X(SD) chromosome. This result suggests that the amount of the Sd product is not limited with respect to the interacting sites available, that is, the amount is large enough to interact with both of the Rsp(ss) alleles. PMID:2116354

  13. P2Y1 receptor-mediated potentiation of inspiratory motor output in neonatal rat in vitro.

    PubMed

    Alvares, T S; Revill, A L; Huxtable, A G; Lorenz, C D; Funk, G D

    2014-07-15

    PreBötzinger complex inspiratory rhythm-generating networks are excited by metabotropic purinergic receptor subtype 1 (P2Y1R) activation. Despite this, and the fact that inspiratory MNs express P2Y1Rs, the role of P2Y1Rs in modulating motor output is not known for any MN pool. We used rhythmically active brainstem-spinal cord and medullary slice preparations from neonatal rats to investigate the effects of P2Y1R signalling on inspiratory output of phrenic and XII MNs that innervate diaphragm and airway muscles, respectively. MRS2365 (P2Y1R agonist, 0.1 mm) potentiated XII inspiratory burst amplitude by 60 ± 9%; 10-fold higher concentrations potentiated C4 burst amplitude by 25 ± 7%. In whole-cell voltage-clamped XII MNs, MRS2365 evoked small inward currents and potentiated spontaneous EPSCs and inspiratory synaptic currents, but these effects were absent in TTX at resting membrane potential. Voltage ramps revealed a persistent inward current (PIC) that was attenuated by: flufenamic acid (FFA), a blocker of the Ca(2+)-dependent non-selective cation current ICAN; high intracellular concentrations of BAPTA, which buffers Ca(2+) increases necessary for activation of ICAN; and 9-phenanthrol, a selective blocker of TRPM4 channels (candidate for ICAN). Real-time PCR analysis of mRNA extracted from XII punches and laser-microdissected XII MNs revealed the transcript for TRPM4. MRS2365 potentiated the PIC and this potentiation was blocked by FFA, which also blocked the MRS2365 potentiation of glutamate currents. These data suggest that XII MNs are more sensitive to P2Y1R modulation than phrenic MNs and that the P2Y1R potentiation of inspiratory output occurs in part via potentiation of TRPM4-mediated ICAN, which amplifies inspiratory inputs. PMID:24879869

  14. 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

  15. 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

  16. 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

  17. 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.

  18. 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

  19. Spectroscopic study of metallic magnetism in single-crystalline Nb1 -yFe2 +y

    NASA Astrophysics Data System (ADS)

    Rauch, D.; Kraken, M.; Litterst, F. J.; Süllow, S.; Luetkens, H.; Brando, M.; Förster, T.; Sichelschmidt, J.; Neubauer, A.; Pfleiderer, C.; Duncan, W. J.; Grosche, F. M.

    2015-05-01

    We have investigated single crystals and polycrystals from the series Nb1 -yFe2 +y , -0.004 ≤y ≤0.018 , by electron spin resonance, muon spin relaxation, and Mössbauer spectroscopy. Our data establish that at lowest temperatures all samples exhibit bulk magnetic order. Slight Fe excess induces low-moment ferromagnetism, consistent with bulk magnetometry, while Nb-rich and stoichiometric NbFe2 display spin density wave order with small magnetic moment amplitudes of order ˜0.001 -0.01 μB/Fe . This provides microscopic evidence for a modulated magnetic state on the border of ferromagnetism in NbFe2.

  20. 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

  1. Oxygen and cation ordered perovskite, Ba 2Y 2Mn 4O 11

    NASA Astrophysics Data System (ADS)

    Karppinen, M.; Okamoto, H.; Fjellvåg, H.; Motohashi, T.; Yamauchi, H.

    2004-06-01

    A three-step route has been developed for the synthesis of a new oxygen-ordered double perovskite, BaYMn 2O 5.5 or Ba 2Y 2Mn 4O 11. (i) The A-site cation ordered perovskite, BaYMn 2O 5+ δ, is first synthesized at δ≈0 by an oxygen-getter-controlled low-O 2-pressure encapsulation technique utilizing FeO as the getter for excess oxygen. (ii) The as-synthesized, oxygen-deficient BaYMn 2O 5.0 phase is then readily oxygenated to the δ≈1 level by means of 1-atm-O 2 annealing at low temperatures. (iii) By annealing this fully oxygenated BaYMn 2O 6.0 in flowing N 2 gas at moderate temperatures the new intermediate oxygen content oxide, BaYMn 2O 5.5 or Ba 2Y 2Mn 4O 11, is finally obtained. From thermogravimetric observation it is seen that the final oxygen depletion from δ≈1.0 to 0.5 occurs in a single sharp step about 600°C, implying that the oxygen stoichiometry of BaYMn 2O 5+ δ is not continuously tunable within 0.5< δ<1.0. For BaYMn 2O 5.5 synchrotron X-ray diffraction analysis reveals an orthorhombic crystal lattice and a long-range ordering of the excess oxygen atoms in the YO 0.5 layer. The magnetic behavior of BaYMn 2O 5.5 (with a ferromagnetic transition at ˜133 K) is found different from those previously reported for the known phases, BaYMn 2O 5.0 and BaYMn 2O 6.0.

  2. 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.

  3. 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

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

    PubMed

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

    2014-10-01

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

  5. 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

  6. Order-Order Transition of C → sdG → sL → S in ABC Triblock Copolymer Thin Film Induced by Solvent Vapor.

    PubMed

    Luo, Chunxia; Huang, Weihuan; Han, Yanchun

    2009-04-01

    The morphology transition of polystyrene-block-poly(butadiene)-block-poly(2-vinylpyridine) (SBV) triblock thin film induced in benzene vapor showing weak selectivity for PS is investigated. The order-order transitions (OOT) in the sequence of core-shell cylinders (C), sphere in 'diblock gyroid' (sdG), sphere in lamella (sL) and sphere (S) are observed. The projection along (111) direction in Gyroid phase (sdG(111)) is found to epitaxially grow from C(001) in the film. Instead of sdG(111), sdG(110)(0.1875) develops to the phase of sL. Consequently, the film experiences the transition sequence of sdG(111) → sdG(211) → sdG(110)(0.25)  → sdG(110)(0.1875) between C and sL. The mechanism is analyzed from the total surface area of the blocks.

  7. 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

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

    PubMed Central

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

    2016-01-01

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

  9. Electronic origin of the step-like character of the discharge curve for NaxCoO2-y cathode

    NASA Astrophysics Data System (ADS)

    Molenda, Janina; Baster, Dominika; Gutowska, Maria U.; Szewczyk, Andrzej; Puźniak, Roman; Tobola, Janusz

    2014-10-01

    This paper shows electronic approach to an explanation of the step-like character of the discharge/charge curve of Na/Na+/NaxCoO2-y battery. On a basis of comprehensive experimental studies of physicochemical properties of NaxCoO2-y cathode material (XRD, electrical conductivity, thermoelectric power, electronic specific heat) supported by calculations performed using the Korringa-Kohn-Rostoker method with the coherent potential approximation to account for chemical disorder, it has been shown that the observed step-like character of the discharge curve reflects the variation of the chemical potential of electrons (Fermi level) in the density of states of NaxCoO2-y, which is anomalously perturbed by a presence of the oxygen vacancy defects and sodium ordering.

  10. The P2Y2 receptor mediates uptake of matrix-retained and aggregated low density lipoprotein in primary vascular smooth muscle cells

    PubMed Central

    Dissmore, Tixieanna; Seye, Cheikh I.; Medeiros, Denis M.; Weisman, Gary A.; Bardford, Barry; Mamedova, Laman

    2016-01-01

    Background and aims The internalization of aggregated low-density lipoproteins (agLDL) mediated by low-density lipoprotein receptor related protein (LRP1) may involve the actin cytoskeleton in ways that differ from the endocytosis of soluble LDL by the LDL receptor (LDLR). This study aims to define novel mechanisms of agLDL uptake through modulation of the actin cytoskeleton, to identify molecular targets involved in foam cell formation in vascular smooth muscle cells (VSMCs). The critical observation that formed the basis for these studies is that under pathophysiological conditions, nucleotide release from blood-derived and vascular cells activates SMC P2Y2 receptors (P2Y2Rs) leading to rearrangement of the actin cytoskeleton and cell motility. Therefore, we tested the hypothesis that P2Y2R activation mediates agLDL uptake by VSMCs. Methods Primary VSMCs were isolated from aortas of wild type (WT) C57BL/6 and.P2Y2R−/− mice to investigate whether P2Y2R activation modulates LRP1 expression. Cells were transiently transfected with cDNA encoding a hemagglutinin-tagged (HA-tagged) WT P2Y2R, or a mutant P2Y2R that unlike the WT P2Y2R does not bind the cytoskeletal actin-binding protein filamin-A (FLN-A). Results P2Y2R activation significantly increased agLDL uptake, and LRP1 mRNA expression decreased in P2Y2R−/− VSMCs versus WT. SMCs, expressing P2Y2R defective in FLN-A binding, exhibit 3-fold lower LDLR expression levels than SMCs expressing WT P2Y2R, while cells transfected with WT P2Y2R show greater agLDL uptake in both WT and P2Y2R−/− VSMCs versus cells transfected with the mutant P2Y2R. Conclusions Together, these results show that both LRP1 and LDLR expression and agLDL uptake are regulated by P2Y2R in VSMCs, and that agLDL uptake due to P2Y2R activation is dependent upon cytoskeletal reorganization mediated by P2Y2R binding to FLN-A. PMID:27522265

  11. Apical targeting of the P2Y(4) receptor is directed by hydrophobic and basic residues in the cytoplasmic tail.

    PubMed

    DuBose, D Ross; Wolff, Samuel C; Qi, Ai-Dong; Naruszewicz, Izabela; Nicholas, Robert A

    2013-02-01

    The P2Y(4) receptor is selectively targeted to the apical membrane in polarized epithelial cell lines and has been shown to play a key role in intestinal chloride secretion. In this study, we delimit a 23 amino acid sequence within the P2Y(4) receptor C-tail that directs its apical targeting. Using a mutagenesis approach, we found that four hydrophobic residues near the COOH-terminal end of the signal are necessary for apical sorting, whereas two basic residues near the NH(2)-terminal end of the signal are involved to a lesser extent. Interestingly, mutation of the key hydrophobic residues results in a basolateral enrichment of the receptor construct, suggesting that the apical targeting sequence may prevent insertion or disrupt stability of the receptor at the basolateral membrane. The signal is not sequence specific, as an inversion of the 23 amino acid sequence does not disrupt apical targeting. We also show that the apical targeting sequence is an autonomous signal and is capable of redistributing the normally basolateral P2Y(12) receptor, suggesting that the apical signal is dominant over the basolateral signal in the main body of the P2Y(12) receptor. The targeting sequence is unique to the P2Y(4) receptor, and sequence alignments of the COOH-terminal tail of mammalian orthologs reveal that the hydrophobic residues in the targeting signal are highly conserved. These data define the novel apical sorting signal of the P2Y(4) receptor, which may represent a common mechanism for trafficking of epithelial transmembrane proteins.

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

    SciTech Connect

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

    2013-01-01

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

  13. P2Y12 receptor expression is a critical determinant of functional responsiveness to ATX's MORFO domain.

    PubMed

    Dennis, Jameel; Morgan, Magdalena K; Graf, Martin R; Fuss, Babette

    2012-06-01

    In the central nervous system, the formation of the myelin sheath and the differentiation of the myelinating cells, namely oligodendrocytes, are regulated by complex signaling networks that involve purinergic receptors and the extracellular matrix. However, the exact nature of the molecular interactions underlying these networks still needs to be defined. In this respect, the data presented here reveal a signaling mechanism that is characterized by an interaction between the purinergic P2Y(12) receptor and the matricellular extracellular matrix protein autotaxin (ATX), also known as ENPP2, phosphodiesterase-Iα/ATX, or lysoPLD. ATX has been previously described by us to mediate intermediate states of oligodendrocyte adhesion and to enable changes in oligodendrocyte morphology that are thought to be crucial for the formation of a fully functional myelin sheath. This functional property of ATX is mediated by ATX's modulator of oligodendrocyte remodeling and focal adhesion organization (MORFO) domain. Here, we show that the expression of the P2Y(12) receptor is necessary for ATX's MORFO domain to exert its effects on differentiating oligodendrocytes. In addition, our data demonstrate that exogenous expression of the P2Y(12) receptor can render cells responsive to the known effects of ATX's MORFO domain, and they identify Rac1 as an intracellular factor mediating the effect of ATX-MORFO-P2Y(12) signaling on the assembly of focal adhesions. Our data further support the idea that a physical interaction between ATX and the P2Y(12) receptor provides the basis for an ATX-MORFO-P2Y(12) signaling axis that is crucial for mediating cellular states of intermediate adhesion and morphological/structural plasticity.

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

    PubMed

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

    2015-03-23

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

  15. 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.

  16. 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.

  17. Can chest trauma patients provide breath sample with Lion SD-400 Alcometer?

    PubMed

    Rathinam, Sridhar; Luke, David; Nanjaiah, Prakash; Kalkat, Maninder S; Steyn, Richard S

    2009-06-01

    Various investigators have addressed the minimum lung function required to activate breathalyzers, and the impact of comorbid respiratory illness. We postulated that subjects with significant chest trauma may have difficulty in providing an adequate breathalyzer sample. A prospective self-controlled study of 20 patients who underwent thoracotomy was conducted between August 2005 and December 2005, using a Lion Alcometer SD-400. The mean age of the patients was 69.3 years (range, 37-83 years). Preoperatively, their mean forced expiratory volume was 1.97 L (range, 1.19-2.46 L), and peak expiratory flow rate was 240 L min(-1) (range, 126-520 L min(-1)). Postoperatively, mean forced expiratory volume was 1.14 L (range, 0.34-2.2 L) and peak expiratory flow rate was 179 L min(-1) (range, 36-492 L min(-1)). These decreases were highly significant. All patients activated the breathalyzer device preoperatively, but only 2 (10%) could activate it postoperatively. Extrapolating this to patients with chest injury, most may find it impossible to activate breathalyzers. PMID:19643853

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. Mercury(II) and methyl mercury speciation on Streptococcus pyogenes loaded Dowex Optipore SD-2.

    PubMed

    Tuzen, Mustafa; Uluozlu, Ozgur Dogan; Karaman, Isa; Soylak, Mustafa

    2009-09-30

    A solid phase extraction procedure based on speciation of mercury(II) and methyl mercury on Streptococcus pyogenes immobilized on Dowex Optipore SD-2 has been established. Selective and sequential elution with 0.1 mol L(-1) HCl for methyl mercury and 2 mol L(-1) HCl for mercury(II) were performed at pH 8. The determination of mercury levels was performed by cold vapour atomic absorption spectrometry (CVAAS). Optimal analytical conditions including pH, amounts of biosorbent, sample volumes, etc., were investigated. The influences of the some alkaline and earth alkaline ions and some transition metals on the recoveries were also investigated. The capacity of biosorbent for mercury(II) and methyl mercury was 4.8 and 3.4 mg g(-1). The detection limit (3 sigma) of the reagent blank for mercury(II) and methyl mercury was 2.1 and 1.5 ng L(-1). Preconcentration factor was calculated as 25. The relative standard deviations of the procedure were below 7%. The validation of the presented procedure is performed by the analysis of standard reference material (NRCC-DORM 2 Dogfish Muscle). The procedure was successfully applied to the speciation of mercury(II) and methyl mercury in natural water and environmental samples.

  8. Platelet P2Y12 receptors enhance signalling towards procoagulant activity and thrombin generation. A study with healthy subjects and patients at thrombotic risk.

    PubMed

    van der Meijden, Paola E J; Feijge, Marion A H; Giesen, Peter L A; Huijberts, Maya; van Raak, Lisette P M; Heemskerk, Johan W M

    2005-06-01

    Activated platelets participate in arterial thrombosis by forming aggregates and potentiating the coagulation through exposure of procoagulant phosphatidylserine. The function of the two receptors for ADP, P2Y(1) and P2Y(12), is well-established in aggregation, but is incompletely understood in the platelet procoagulant response. We established that, in PRP from healthy subjects, ADP accelerated and potentiated tissue factor induced thrombin generation exclusively via stimulation of P2Y(12) and not via P2Y(1) receptors. The P2Y(12) receptors also mediated the potentiating effect of PAR-1 stimulation on thrombin generation. Furthermore, ADP enhanced in a P2Y(12)-dependent manner the Ca(2+) response induced by thrombin, which was either added externally or generated in-situ. This ADP effect was in part dependent of phosphoinositide 3-kinase and was paralleled by increased phosphatidylserine exposure. In PRP from (young) patients with either stroke or type-II diabetes, platelet-dependent thrombin generation was similarly enhanced byADP or SFLLRN as in healthy subjects. In PRP from stroke patients of older age, the P2Y(12)-mediated contribution to thrombin generation was variably reduced by two weeks of clopidogrel medication. Remaining P2Y(12) activity after medication correlated with remaining P2Y(12)-dependent P-selectin exposure, i.e. Ca(2+)-dependent secretion, likely due to incomplete antagonism of P2Y(12) receptors. Together, these results indicate that physiological platelet agonists amplify phosphatidylserine exposure and subsequent thrombin generation by release of ADP and P2Y(12)-receptor stimulation. This P2Y(12) response is accomplished by a novel Ca(2+) signalling pathway. It is similarly active in platelets from control subjects and patients at thrombotic risk. Finally, the thrombogram method is useful for measuring incomplete P2Y(12) inhibition with clopidogrel. PMID:15968399

  9. Arg333 and Arg334 in the COOH terminus of the human P2Y1 receptor are crucial for Gq coupling.

    PubMed

    Ding, Zhongren; Tuluc, Florin; Bandivadekar, Kavita R; Zhang, Lili; Jin, Jianguo; Kunapuli, Satya P

    2005-03-01

    The P2Y(1) ADP receptor activates G(q) and causes increases in intracellular Ca(2+) concentration through stimulation of PLC. In this study, we investigated the role of the amino acid residues in the COOH terminus of the human P2Y(1) receptor in G(q) activation. Stimulation of Chinese hamster ovary (CHO-K1) cells stably expressing the wild-type human P2Y(1) receptor (P2Y(1)-WT cells), P2Y(1)-DeltaR340-L373, or P2Y(1)-DeltaD356-L373 with 2-methylthio-ADP (2-MeSADP) caused inositol phosphate production. In contrast, cells expressing P2Y(1)-DeltaT330-L373, a mutant lacking the entire COOH terminus, completely lost their response to 2-MeSADP. Similar data were obtained by using these cell lines and measuring Ca(2+) mobilization upon stimulation with 2-MeSADP, indicating that the 10 amino acids (330TFRRRLSRAT339) in the COOH terminus of the human P2Y(1) receptor are essential for G(q) coupling. Radioligand binding demonstrated that both the P2Y(1)-WT and P2Y(1)-DeltaT330-L373-expressing cells have almost equal binding of [(3)H]MRS2279, a P2Y(1) receptor antagonist, indicating that COOH-terminal truncation did not drastically affect the conformation of the receptor. CHO-K1 cells expressing a chimeric P2Y(12) receptor with the P2Y(1) COOH terminus failed to elicit G(q) functional responses, indicating that the P2Y(1) COOH terminus is essential but not sufficient for G(q) activation. Finally, cells expressing a double-mutant P2Y(1) receptor (R333A/R334A) in the conserved BBXXB region of the COOH terminus of the G(q)-activating P2Y receptors completely lost their functional ability to activate G(q). We conclude that the two arginine residues (R333R334) in the COOH terminus of the human P2Y(1) receptor are essential for G(q) coupling.

  10. Formation and tidal synchronization of sdB stars in binaries an asteroseismic investigation using Kepler Observations

    NASA Astrophysics Data System (ADS)

    Pablo, Herbert William

    Subdwarf B (sdB) stars are low mass (0.5 M sun) helium burning stars with thin hydrogen envelopes and Teff 22000-40000 K. Many of these stars are found in binary systems. One common proposed formation mechanism is common envelope (CE) ejection, where the companion spirals deep into the star's envelope ejecting the outer layers and forming a close binary system. In this dissertation, we use short cadence (tint=58.86 s) Kepler photometric time-series data to study three close sdB binaries with P ≈ 10 hours and g-mode pulsations. Asteroseismic analysis finds that each system has a constant period spacing of ΔP ≈ 250 s consistent with single sdB stars. This analysis also shows the presence of rotational multiplets which we used to find the rotation period. In all three cases the binary system is far from tidal synchronization with a rotation period an order of magnitude longer than the orbital period. These observations agree with predictions using the Zahn formulation of tidal evolution which predicts a synchronization time longer than the sdB lifetime (108 yr). We use this synchronization time to backtrack the sdB's rotation history and find its initial rotation period as it is first exiting the CE. This is one of the only observationally based constraints that has been placed on CE evolution. Preliminary investigations of single sdB stars show similar rotation periods, indicating that the rotation period may be independent of the formation channel.

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. Cs vacancy ordering and properties of phase separated Csx Fe2-y Se2

    NASA Astrophysics Data System (ADS)

    Chmaissem, Omar; Taddei, K. M.; Rosenkranz, S.; Osborn, R.; Claus, H.; Sturza, M.; Chung, D. Y.; Kanatzidis, M. G.; Cao, H. B.

    Iron-based selenides are among the most complex and least understood superconductors. At high temperature, a '122'-type structure with random iron vacancies undergoes a complex iron vacancy ordering scheme below ~500K causing the material to phase separate into A2Fe4Se5, known as the 245 phase, and a minority A-site deficient and fully iron stoichiometric AxFe2Se2 phase (122). At slightly lower temperatures, the material undergoes another transition with the Fe spins of the main '245' phase ordering into an exotic checkerboard-type magnetic structure with a large magnetic moment. The minority 122 phase is reported to either remain nonmagnetic or to become magnetic below ~200K. At temperatures below ~30K, the magnetic material becomes superconducting and the two states appear to coexist. I will present and discuss our recent synthesis and characterization of high quality CsxFe2-ySe2 single crystals and bulk samples with various Tc's that form a relatively large superconducting dome. I will discuss our findings of a previously unseen three dimensional cesium vacancy ordering in the low temperature 122 phase in addition to hosting superconductivity. At ANL, work supported by the US DOE Office of Science, MSED.

  1. Local disorder and superconductivity in KxFe2-ySe2

    NASA Astrophysics Data System (ADS)

    Louca, Despina; Park, Keeseong; Li, Bing; Yan, Y.-Q.; Neuefeind, Joerg

    2014-03-01

    In the KxFe2-ySe2 family of Fe-based superconductors, superconductivity is observed between a semi-metallic region below x ~ 0.7 and an insulating and antiferromagnetic region above x ~ 0.85. By probing the local structure we observe that superconductivity emerges in a locally distorted Fe sublattice that accommodates two kinds of bonding 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 K, a continuous transition from the short to the 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 superconductivity is intertwined with magnetism, appearing at the crossover from metallic to insulating conditions and is not due to phase separation.

  2. Calcium signaling and the novel anti-proliferative effect of the UTP-sensitive P2Y11 receptor in rat cardiac myofibroblasts.

    PubMed

    Certal, Mariana; Vinhas, Adriana; Pinheiro, Ana Rita; Ferreirinha, Fátima; Barros-Barbosa, Aurora Raquel; Silva, Isabel; Costa, Maria Adelina; Correia-de-Sá, Paulo

    2015-11-01

    During myocardial ischemia and reperfusion both purines and pyrimidines are released into the extracellular milieu, thus creating a signaling wave that propagates to neighboring cells via membrane-bound P2 purinoceptors activation. Cardiac fibroblasts (CF) are important players in heart remodeling, electrophysiological changes and hemodynamic alterations following myocardial infarction. Here, we investigated the role UTP on calcium signaling and proliferation of CF cultured from ventricles of adult rats. Co-expression of discoidin domain receptor 2 and α-smooth muscle actin indicate that cultured CF are activated myofibroblasts. Intracellular calcium ([Ca(2+)]i) signals were monitored in cells loaded with Fluo-4 NW. CF proliferation was evaluated by the MTT assay. UTP and the selective P2Y4 agonist, MRS4062, caused a fast desensitizing [Ca(2+)]i rise originated from thapsigargin-sensitive internal stores, which partially declined to a plateau providing the existence of Ca(2+) in the extracellular fluid. The biphasic [Ca(2+)]i response to UTP was attenuated respectively by P2Y4 blockers, like reactive blue-2 and suramin, and by the P2Y11 antagonist, NF340. UTP and the P2Y2 receptor agonist MRS2768 increased, whereas the selective P2Y11 agonist NF546 decreased, CF growth; MRS4062 was ineffective. Blockage of the P2Y11 receptor or its coupling to adenylate cyclase boosted UTP-induced CF proliferation. Confocal microscopy and Western blot analysis confirmed the presence of P2Y2, P2Y4 and P2Y11 receptors. Data indicate that besides P2Y4 and P2Y2 receptors which are responsible for UTP-induced [Ca(2+)]i transients and growth of CF, respectively, synchronous activation of the previously unrecognized P2Y11 receptor may represent an important target for anti-fibrotic intervention in cardiac remodeling.

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

    PubMed

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

    2015-07-15

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

  4. P2Y4 Nucleotide Receptor in Neuronal Precursors Induces Glutamatergic Subtype Markers in Their Descendant Neurons

    PubMed Central

    Uda, Youichi; Xu, Shuai; Matsumura, Takafumi; Takei, Yoshinori

    2016-01-01

    Summary Neural stem cells (NSCs) produce all neuronal subtypes involved in the nervous system. The mechanism regulating their subtype selection is not fully understood. We found that the expression of the nucleotide receptor P2Y4 was transiently augmented in the course of neuronal differentiation of mouse embryonic stem cells (ESCs), which was after loss of pluripotency but prior to terminal differentiation of neurons. The activation of P2Y4 in the differentiating ESCs resulted in an increased proportion of neurons expressing vesicular glutamate transporter (vGluT), a marker of glutamatergic subtype. A subpopulation of type 2 NSCs of the adult mouse hippocampus expressed P2Y4. Its activation induced the expression of glutamatergic subtype markers, vGluT and TBR1, in their descendant neurons. Reciprocally, inhibition of the P2Y4 signaling abolished the effects of nucleotides on those expressions. Our results provide evidence that differentiating NSCs pass through a stage in which nucleotides can affect subtype marker expression of their descendant neurons. PMID:26972684

  5. BF0801, a novel adenine derivative, inhibits platelet activation via phosphodiesterase inhibition and P2Y12 antagonism.

    PubMed

    Zhang, Si; Hu, Liang; Du, Hongguang; Guo, Yan; Zhang, Yan; Niu, Haixia; Jin, Jianguo; Zhang, Jian; Liu, Junling; Zhang, Xiaohui; Kunapuli, Satya P; Ding, Zhongren

    2010-10-01

    Though antiplatelet drugs are proven beneficial to patients with coronary heart disease and stroke, more effective and safer antiplatelet drugs are still needed. In this study we report the antiplatelet effects and mechanism of BF0801, a novel adenine derivative. BF0801 dramatically inhibited platelet aggregation and ATP release induced by ADP, 2MeSADP, AYPGKF, SFLLRN or convulxin without affecting shape change in vitro . It also potentiated the inhibitory effects of adenosine-based P2Y12 antagonist AR-C69931MX or phosphodiesterase (PDE) inhibitor IBMX on platelet aggregation. The cAMP levels in both resting and forskolin-stimulated platelets were increased by BF0801 suggesting its PDE inhibitor activity, which is further confirmed by the concentration-dependent suppression of BF0801 on the native and recombinant PDE. Similar to AR-C69931MX, BF0801 drastically inhibited 2MeSADP- induced adenylyl cyclase inhibition in platelets indicating its P2Y12 antagonism activity, which is substantiated by the inhibition of BF0801 on the interaction between ADP and P2Y12 receptor expressed in CHO-K1 cells measured by atomic force microscopy. Moreover, we confirmed the antiplatelet effects of BF0801 using platelets from rats intravenously given BF0801. In summary, for the first time we developed a novel adenine derivative bearing dual activities of PDE inhibition and P2Y12 antagonism, which may have therapeutic advantage as a potential antithrombotic drug. PMID:20806121

  6. Inositol triphosphate-mediated Ca2+ signals direct purinergic P2Y receptor regulation of neuronal ion channels.

    PubMed

    Zaika, Oleg; Tolstykh, Gleb P; Jaffe, David B; Shapiro, Mark S

    2007-08-15

    Purinergic P2Y receptors are one of four types of G(q/11)-coupled receptors in rat superior cervical ganglia (SCG) sympathetic neurons. In cultured SCG neurons, purinergic and bradykinin suppression of I(M) were similar in magnitude and somewhat less than that by muscarinic agonists. The effects of the P2Y receptor agonist UTP on neuronal excitability and discharge properties were studied. Under current clamp, UTP increased action potential (AP) firing in response to depolarizing current steps, depolarized the resting potential, decreased the threshold current required to fire an AP, and decreased spike-frequency adaptation. These effects were very similar to those resulting from bradykinin stimulation and not as profound as from muscarinic stimulation or full M-current blockade. We then examined the P2Y mechanism of action. Like bradykinin, but unlike muscarinic, purinergic stimulation induced rises in intracellular [Ca(2+)](i). Tests using expression of IP(3)"sponge" or IP(3) phosphatase constructs implicated IP(3) accumulation as necessary for purinergic suppression of I(M). Overexpression of wild-type or dominant-negative calmodulin (CaM) implicated Ca(2+)/CaM in the purinergic action. Both sets of results were similar to bradykinin, and opposite to muscarinic, suppression. We also examined modulation of Ca(2+) channels. As for bradykinin, purinergic stimulation did not suppress I(Ca), unless neuronal calcium sensor-1 (NCS-1) activity was blocked by a dominant-negative NCS-1 construct. Our results indicate that P2Y receptors modulate M-type channels in SCG cells via IP(3)-mediated [Ca(2+)](i) signals in concert with CaM and not by depletion of phosphatidylinositol-4, 5-biphosphate. We group purinergic P2Y and bradykinin B(2) receptors together as having a common mode of action.

  7. 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:...

  8. 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...

  9. 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... specific information is available, these factors can be assumed to represent the most common bolted...

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

    PubMed

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

    2015-01-01

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

  11. TGF-β-RI Kinase Inhibitor SD-208 Reduces the Development and Progression of Melanoma Bone Metastases

    PubMed Central

    Mohammad, Khalid S.; Javelaud, Delphine; Fournier, Pierrick G. J.; Niewolna, Maria; McKenna, C. Ryan; Peng, Xiang H.; Duong, Vu; Dunn, Lauren K.; Mauviel, Alain; Guise, Theresa A.

    2010-01-01

    Melanoma often metastasizes to bone where it is exposed to high concentrations of TGF-β. Constitutive Smad signaling occurs in human melanoma. Because TGF-β promotes metastases to bone by several types of solid tumors including breast cancer, we hypothesized that pharmacologic blockade of the TGF-β signaling pathway may interfere with the capacity of melanoma cells to metastasize to bone. In this study, we tested the effect of a small molecule inhibitor of TGF-β receptor I kinase (TβRI), SD-208, on various parameters affecting the development and progression of melanoma, both in vitro and in a mouse model of human melanoma bone metastasis. In melanoma cell lines, SD-208 blocked TGF-β induction of Smad3 phosphorylation, Smad3/4-specific transcription, Matrigel invasion and expression of the TGF-β target genes PTHrP, IL-11, CTGF and RUNX2. To assess effects of SD-208 on melanoma development and metastasis, nude mice were inoculated with 1205Lu melanoma cells into the left cardiac ventricle and drug was administered by oral gavage on prevention or treatment protocols. SD-208 (60mg/kg/day), started 2 days before tumor inoculation prevented the development of osteolytic bone metastases compared with vehicle. In mice with established bone metastases, the size of osteolytic lesions was significantly reduced after 4 weeks treatment with SD-208 compared to vehicle-treated mice. Our results demonstrate that therapeutic targeting of TGF-β may prevent the development of melanoma bone metastases and decrease the progression of established osteolytic lesions. PMID:21084275

  12. 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.

  13. 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

  14. 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

  15. Vortex state in NaxCoO2.yH2O: px+/-ipy-wave versus d(x2-y2)+/-id xy-wave pairing.

    PubMed

    Han, Qiang; Wang, Z D; Wang, Qiang-Hua; Xia, Tianlong

    2004-01-16

    Based on an effective Hamiltonian specified in the triangular lattice with possible p(x)+/-ip(y)- or dx(2)(-y(2))+/-id(xy)-wave pairing, which has close relevance to the newly discovered Na0.35CoO2.yH(2)O, the electronic structure of the vortex state is studied by solving the Bogoliubov-de Gennes equations. It is found that p(x)+/-ip(y) wave is favored for the electron doping as the hopping integral t<0. The lowest-lying vortex bound states are found to have, respectively, zero and positive energies for p(x)+/-ip(y)- and dx(2)(-y(2))+/-id(xy)-wave superconductors, whose vortex structures exhibit the intriguing sixfold symmetry. In the presence of strong on-site repulsion, the antiferromagnetic order and local ferromagnetic moment are induced around the vortex cores for the former and the latter, respectively, both of which cause the splitting of the local density of states peaks due to the lifting of spin degeneracy.

  16. Sustained Release of Prostaglandin E2 in Fibroblasts Expressing Ectopically Cyclooxygenase 2 Impairs P2Y-Dependent Ca2+-Mobilization

    PubMed Central

    Pimentel-Santillana, María; Través, Paqui G.; Pérez-Sen, Raquel; Delicado, Esmerilda G.; Martín-Sanz, Paloma; Miras-Portugal, María Teresa; Boscá, Lisardo

    2014-01-01

    The nucleotide uridine trisphosphate (UTP) released to the extracellular milieu acts as a signaling molecule via activation of specific pyrimidine receptors (P2Y). P2Y receptors are G protein-coupled receptors expressed in many cell types. These receptors mediate several cell responses and they are involved in intracellular calcium mobilization. We investigated the role of the prostanoid PGE2 in P2Y signaling in mouse embryonic fibroblasts (MEFs), since these cells are involved in different ontogenic and physiopathological processes, among them is tissue repair following proinflammatory activation. Interestingly, Ca2+-mobilization induced by UTP-dependent P2Y activation was reduced by PGE2 when this prostanoid was produced by MEFs transfected with COX-2 or when PGE2 was added exogenously to the culture medium. This Ca2+-mobilization was important for the activation of different metabolic pathways in fibroblasts. Moreover, inhibition of COX-2 with selective coxibs prevented UTP-dependent P2Y activation in these cells. The inhibition of P2Y responses by PGE2 involves the activation of PKCs and PKD, a response that can be suppressed after pharmacological inhibition of these protein kinases. In addition to this, PGE2 reduces the fibroblast migration induced by P2Y-agonists such as UTP. Taken together, these data demonstrate that PGE2 is involved in the regulation of P2Y signaling in these cells. PMID:25214717

  17. 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

  18. 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

  19. 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.

  20. 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

  1. High platelet reactivity after P2Y12-inhibition in patients with atrial fibrillation and coronary stenting.

    PubMed

    Rilinger, Jonathan; Meyer, Melanie; Schnabel, Katharina; Weik, Patrick; Charlet, Anne; Esser, Jennifer S; Zhou, Qian; Bode, Christoph; Moser, Martin; Diehl, Philipp; Olivier, Christoph B

    2016-11-01

    High platelet reactivity (HPR) after P2Y12-inhibition in patients undergoing coronary stenting is associated with an increased risk for thromboembolic events and coronary death. So far it is not known how HPR affects the clinical outcome of different treatment strategies in patients with atrial fibrillation (AF) undergoing coronary stenting. In this single centre, observational study the antiplatelet effect of P2Y12-inhibitors in AF patients undergoing coronary stenting was investigated using impedance aggregometry. Patients received either dual antiplatelet therapy (DAPT) or triple therapy (TT). HPR was defined as the ratio of ADP-to TRAP-induced aggregation (r-ADP-agg) ≥50 %. Thromboembolic and bleeding events were assessed within the first 30 days after stenting. Out of 910 screened patients 167 patients were available for the present analysis. HPR was found in 5 of 43 (12 %) patients treated with DAPT and in 18 of 124 (15 %) patients treated with TT. In patients receiving TT, HPR was not a risk factor for thromboembolic events compared to patients with adequate response to P2Y12-inhibitors (6 vs. 8 %, p = 0.712). There was a trend for less bleeding events in patients with HPR compared to r-ADP-agg <50 % in the TT group (0 vs. 16 %, p = 0.077). Our data suggest that HPR after P2Y12-antagonism in patients receiving TT due to AF and coronary stenting might protect from bleeding without increasing thromboembolic risk. Future studies will need to investigate if patients with AF receiving coronary stenting benefit from a reduction of antithrombotic therapy.

  2. UDP-Sugars as Extracellular Signaling Molecules: Cellular and Physiologic Consequences of P2Y14 Receptor Activation

    PubMed Central

    Lazarowski, Eduardo R.

    2015-01-01

    UDP-sugars, which are indispensable for protein glycosylation reactions in cellular secretory pathways, also act as important extracellular signaling molecules. We discuss here the broadly expressed P2Y14 receptor, a G-protein–coupled receptor targeted by UDP sugars, and the increasingly diverse set of physiologic responses discovered recently functioning downstream of this receptor in many epithelia as well as in immune, inflammatory, and other cells. PMID:25829059

  3. Systematics of band moment of inertia of yrast and excited SD bands of even-even nuclei in A~150 mass region

    NASA Astrophysics Data System (ADS)

    Sharma, Neha; Mittal, H. M.

    2015-07-01

    A four parameter formula has been applied to all the yrast and excited superdeformed (SD) bands of even-even nuclei in the A 150 mass region to obtain band moment of inertia J0. In even-even nuclei, totally three yrast SD bands and 16 excited SD bands have been fitted. The measured Qt values and hence the axes ratios have been used to calculate the rigid body J0 values and compared with the fitted values of J0. It is interesting to look at the yrast SD band 152Dy(1), the doubly magic SD nucleus and the first one to be discovered that the J0 values are quite larger than that extracted from Qt measurement. We found that all the excited SD bands in even-even nuclei are signature partner SD bands because the J0 value of each signature partner SD band is almost identical. Among all these excited SD bands, 150Gd(4) is found to be super-rigid in nature having J0 value larger than that observed from the measured Qt value.

  4. 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

  5. Relation between the structural phase transition and superconductivity in CuxIrTe2 -ySey

    NASA Astrophysics Data System (ADS)

    Kamitani, M.; Sakai, H.; Tokura, Y.; Ishiwata, S.

    2016-10-01

    We have investigated the relation between structural transition with Ir-dimer formation and superconductivity in IrTe2 by combining the Se substitution and the Cu intercalation. Regardless of the structural transition temperature (Ts), which increases with increasing the Se content (y ) in IrTe2 -ySey , superconductivity emerges robustly by the Cu intercalation. As the Cu content x in CuxIrTe2 -ySey increases, Ts tends to decrease, followed by the emergence of superconductivity with showing the highest critical temperature (Tc) at the optimum Cu concentration (xopt) close to the structural phase boundary. Based on the transport and thermodynamic properties, the electron-phonon coupling constant is found to be enhanced near the structural phase boundary, which suggests an essential role of the structural instability for the superconductivity in doped IrTe2. With increasing y from 0 to 0.5 in CuxIrTe2 -ySey , Ts at x =0 increases by about 80%, whereas Tc at x =xopt decreases by about 20%. This can be understood by the weakening of the interlayer hybridization upon the Se substitution, resulting in the weak but negative correlation between Ts and Tc through y .

  6. Evaluation of antitumor activity of a TGF-beta receptor I inhibitor (SD-208) on human colon adenocarcinoma

    PubMed Central

    2014-01-01

    Background Transforming growth factor-β (TGF-β) pathway is involved in primary tumor progression and in promoting metastasis in a considerable proportion of human cancers such as colorectal cancer (CRC). Therefore, blockage of TGF-β pathway signaling via an inhibitor could be a valuable tool in CRC treatment. Methods To evaluate the efficacy of systemic targeting of the TGF-β pathway for therapeutic effects on CRC, we investigated the effects of a TGβRI (TGF-β receptor 1) or TβRI kinase inhibitor, SD-208, on SW-48, colon adenocarcinoma cells. In this work, in vitro cell proliferation was studied by methyl thiazolyl tetrazolium (MTT) and bromo-2′-deoxyuridine (BrdU) assays. Also, the histopathological and immunohistochemical evaluations were conducted by hematoxylin and eosin, and Ki-67 and CD34 markers were stained, respectively. Results Our results showed no significant reduction in cell proliferation and vessel formation (170 ± 70 and 165 ± 70, P > 0.05) in treated SW-48 cells with SD-208 compared to controls. Conclusion Our data suggested that SD-208 could not significantly reduce tumor growth and angiogenesis in human colorectal cancer model at least using SW-48 cells. PMID:24902843

  7. 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

  8. [Glucose transponer type 1 deficiency síndrome (GLUT-1 SD) treated with ketogenic diet. Report of one case].

    PubMed

    Cornejo, Verónica E; Cabello, Juan Francisco A; Colombo, Marta C; Raimann, Erna B

    2007-05-01

    The glucose transporter type 1 deficiency syndrome (GLUT-1 SD) (OMIM 606777) is an inborn error of metabolism of brain glucose transport. The characteristic clinical manifestations are seizures, hypotonia, developmental delay, microcephaly and hypoglycorrhachia. We report a girl with normal weight and height at birth. At 6 weeks of age she started with convulsions reaching up to 20 myoclonic seizures a day. She was treated with valproate, phenobarbital and carbamazepine without response. Blood analysis including aminoacids and acylcarnitines were all normal. The brain MRI showed frontal atrophy with an increased subarachnoidal space and Electroencephalography was abnormal. Blood glucose was 84 mg/dl and spinal fluid glucose 26 mg/dl with a ratio of 0.31 (Normal Ratio >0.65+/-00.1). These results suggested the diagnosis of GLUT-1 SD, and was confirmed with erythrocyte glucose uptake of 44% (Normal range 80-100%). A molecular study found the mutation 969del, C971T in exon 6 of the gene Glut-1. Treatment with a ketogenic diet was started immediately and after 7 days with this diet seizures ceased. Anticonvulsants were progressively suspended. At present, the patient is 6 years old, she continues on a ketogenic diet and supplements with L-carnitine, lipoic acid, vitamins and minerals. Growth and development are normal with an intelligence quotient of 103. It is concluded that it is necessary to include GLUT-1 SD in the differential diagnosis of children with early seizures that are non responsive to pharmacological treatment.

  9. Purinergic P2Y2 Receptor Control of Tissue Factor Transcription in Human Coronary Artery Endothelial Cells: NEW AP-1 TRANSCRIPTION FACTOR SITE AND NEGATIVE REGULATOR.

    PubMed

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

    2016-01-22

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

  10. P2Y1 receptor activation elicits its partition out of membrane rafts and its rapid internalization from human blood vessels: implications for receptor signaling.

    PubMed

    Norambuena, Andrés; Poblete, M Inés; Donoso, M Verónica; Espinoza, C Sofía; González, Alfonso; Huidobro-Toro, J Pablo

    2008-12-01

    The nucleotide P2Y(1) receptor (P2Y(1)R) is expressed in both the endothelial and vascular smooth muscle cells; however, its plasma membrane microregionalization and internalization in human tissues remain unknown. We report on the role of membrane rafts in P2Y(1)R signaling by using sodium carbonate or OptiPrep sucrose density gradients, Western blot analysis, reduction of tissue cholesterol content, and vasomotor assays of endothelium-denuded human chorionic arteries. In tissue extracts prepared either in sodium carbonate or OptiPrep, approximately 20 to 30% of the total P2Y(1)R mass consistently partitioned into raft fractions and correlated with vasomotor activity. Vessel treatment with methyl beta-cyclodextrin reduced the raft partitioning of the P2Y(1)R and obliterated the P2Y(1)R-mediated contractions but not the vasomotor responses elicited by either serotonin or KCl. Perfusion of chorionic artery segments with 100 nM 2-methylthio ADP or 10 nM [[(1R,2R,3S,4R,5S)-4-[6-amino-2-(methylthio)-9H-purin-9-yl] 2,3dihydroxybicyclo[3.1.0]hex-1-yl]methyl] diphosphoric acid mono ester trisodium salt (MRS 2365), a selective P2Y(1)R agonist, not only displaced within 4 min the P2Y(1)R localization out of membrane rafts but also induced its subsequent internalization. 2'-Deoxy-N(6)-methyladenosine 3',5'-bisphosphate tetrasodium salt (MRS 2179), a specific P2Y(1)R antagonist, did not cause a similar displacement but blocked the agonist-induced exit from rafts. Neither adenosine nor uridine triphosphate displaced the P2Y(1)R from the membrane raft, further evidencing the pharmacodynamics of the receptor-ligand interaction. Vascular reactivity assays showed fading of the ligand-induced vasoconstrictions, a finding that correlated with the P2Y(1)R exit from raft domains and internalization. These results demonstrate in intact human vascular smooth muscle the association of the P2Y(1)R to membrane rafts, highlighting the role of this microdomain in P2Y(1)R signaling.

  11. 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

  12. Extracellular UDP and P2Y6 function as a danger signal to protect mice from vesicular stomatitis virus infection through an increase in IFN-β production.

    PubMed

    Li, Ruimei; Tan, Binghe; Yan, Yan; Ma, Xiaobin; Zhang, Na; Zhang, Zhi; Liu, Mingyao; Qian, Min; Du, Bing

    2014-11-01

    Extracellular nucleotides that constitute a "danger signal" play an important role in the regulation of immune responses. However, the function and mechanism of extracellular UDP and P2Y6 in antiviral immunity remain unknown. In this study, we demonstrated the in vitro and in vivo protection of UDP/P2Y6 signaling in vesicular stomatitis virus (VSV) infection. First, we demonstrated that VSV-infected cells secrete UDP from the cytoplasm as a danger signal to arouse surrounding cells. Meanwhile, expression of the UDP-specific receptor P2Y6 also was enhanced by VSV. Consequently, UDP protects RAW 264.7 cells, murine embryonic fibroblasts, bone marrow-derived macrophages, and L929 cells from VSV and GFP lentivirus infection. This protection can be blocked by the P2Y6 selective antagonist MRS2578 or IFN-α/β receptor-blocking Ab. VSV-induced cell death and virus replication were both enhanced significantly by knocking down and knocking out P2Y6 in different cells. Mechanistically, UDP facilitates IFN-β secretion through the p38/JNK- and ATF-2/c-Jun-signaling pathways, which are crucial in promoting antiviral immunity. Interestingly, UDP was released through a caspase-cleaved pannexin-1 channel in VSV-induced apoptotic cells and protected cells from infection through P2Y6 receptor in an autocrine or paracrine manner. Furthermore, UDP also protected mice from VSV infection through P2Y6 receptors in an acute neurotropic infection mouse model. Taken together, these results demonstrate the important role of extracellular UDP and P2Y6 as a danger signal in antiviral immune responses and suggest a potential therapeutic role for UDP/P2Y6 in preventing and controlling viral diseases.

  13. P2Y12 receptor gene mutation associated with postoperative hemorrhage in a Greater Swiss Mountain dog.

    PubMed

    Boudreaux, Mary K; Martin, Monica

    2011-06-01

    A novel hereditary disorder of platelets was identified across 5 generations of a family of Greater Swiss Mountain dogs. The first dog identified with the mutation bled excessively following routine ovariohysterectomy and required multiple transfusions. Coagulation screening assays, platelet counts, and von Willebrand factor antigen activity were within reference intervals. Flow cytometric studies indicated that platelets from the affected dog expressed normal levels of glycoproteins IIb and IIIa and responded to 2 platelet-activating agents, convulxin and platelet-activating factor, but not to ADP. Based on DNA studies, a 3 base-pair deletion predicted to result in elimination of a serine from the extracellular domain was identified in the gene encoding P2Y12, an ADP receptor protein located on platelet membranes. Flow cytometric analysis of platelets and studies of DNA performed concurrently on 2 unrelated Greater Swiss Mountain dogs were unremarkable. The mutation was subsequently identified in the sire, the maternal grand-dam, a maternal great grandparent, a paternal great grandparent, and a great-great grandparent. The sire was homozygous, but had not yet been identified as having a hemostatic disorder; the other 4 dogs were carriers. This is the first report of a mutation in the gene encoding the ADP receptor P2Y12 in a domestic animal. P2Y12 is the same receptor targeted by ticlopidine and clopidogrel, platelet inhibitors used in lieu of aspirin in people at risk for cardiovascular disease; thus, spontaneous bleeding is not expected unless there are other contributing factors. This disorder is particularly troublesome because spontaneous hemorrhage is absent to mild in affected dogs; however, following routine surgical procedures or trauma, excessive bleeding could occur and have possible fatal consequences.

  14. 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

  15. [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

  16. 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.

  17. 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

  18. Optimization of the Ni-Cr-Al-Y/ZrO2-Y2O3 thermal barrier system

    NASA Technical Reports Server (NTRS)

    Stecura, S.

    1986-01-01

    The effects of bond and thermal barrier coating compositions, thicknesses, and densities on air plasma spray deposited Ni-Cr-Al-Y/ZrO2-Y2O3 life were evaluated in cyclic furnace oxidation tests at temperatures from 1110 to 1220 C. An empirical relation was developed to give life as a function of the above parameters. The thermal barrier system tested which had the longest life consisted of Ni-35.0 wt pct Cr-5.9 wt pct Al-0.95 wt pct Y bond coating and ZrO2-6.1 wt pct Y2O3 thermal barrier coating.

  19. 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

  20. 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

  1. 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.

  2. The P2Y2 nucleotide receptor mediates vascular cell adhesion molecule-1 expression through interaction with VEGF receptor-2 (KDR/Flk-1).

    PubMed

    Seye, Cheikh I; Yu, Ningpu; González, Fernando A; Erb, Laurie; Weisman, Gary A

    2004-08-20

    UTP stimulates the expression of pro-inflammatory vascular cell adhesion molecule-1 (VCAM-1) in endothelial cells through activation of the P2Y(2) nucleotide receptor P2Y(2)R. Here, we demonstrated that activation of the P2Y(2)R induced rapid tyrosine phosphorylation of vascular endothelial growth factor receptor (VEGFR)-2 in human coronary artery endothelial cells (HCAEC). RNA interference targeting VEGFR-2 or inhibition of VEGFR-2 tyrosine kinase activity abolishes P2Y(2)R-mediated VCAM-1 expression. Furthermore, VEGFR-2 and the P2Y(2)R co-localize upon UTP stimulation. Deletion or mutation of two Src homology-3-binding sites in the C-terminal tail of the P2Y(2)R or inhibition of Src kinase activity abolished the P2Y(2)R-mediated transactivation of VEGFR-2 and subsequently inhibited UTP-induced VCAM-1 expression. Moreover, activation of VEGFR-2 by UTP leads to the phosphorylation of Vav2, a guanine nucleotide exchange factor for Rho family GTPases. Using a binding assay to measure the activity of the small GTPases Rho, we found that stimulation of HCAEC by UTP increased the activity of RhoA and Rac1 (but not Cdc42). Significantly, a dominant negative form of RhoA inhibited P2Y(2)R-mediated VCAM-1 expression, whereas expression of dominant negative forms of Cdc42 and Rac1 had no effect. These data indicate a novel mechanism whereby a nucleotide receptor transactivates a receptor tyrosine kinase to generate an inflammatory response associated with atherosclerosis.

  3. 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.

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

    PubMed

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

    2013-01-01

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

  5. The physical structure of planetary nebulae around sdO stars: Abell 36, DeHt 2, and RWT 152

    NASA Astrophysics Data System (ADS)

    Aller, A.; Miranda, L. F.; Olguín, L.; Vázquez, R.; Guillén, P. F.; Oreiro, R.; Ulla, A.; Solano, E.

    2015-01-01

    We present narrow-band Hα and [O III] images, and high-resolution, long-slit spectra of the planetary nebulae (PNe) Abell 36, DeHt 2, and RWT 152 aimed at studying their morphology and internal kinematics. These data are complemented with intermediate-resolution, long-slit spectra to describe the spectral properties of the central stars and nebulae. The morphokinematical analysis shows that Abell 36 consists of an inner spheroid and two bright point-symmetric arcs; DeHt 2 is elliptical with protruding polar regions and a bright non-equatorial ring; and RWT 152 is bipolar. The formation of Abell 36 and DeHt 2 requires several ejection events including collimated bipolar outflows that probably are younger than and have disrupted the main shell. The nebular spectra of the three PNe show a high excitation and also suggest a possible deficiency in heavy elements in DeHt 2 and RWT 152. The spectra of the central stars strongly suggest an sdO nature and their association with PNe points out that they have most probably evolved through the asymptotic giant branch. We analyse general properties of the few known sdOs associated with PNe and find that most of them are relatively or very evolved PNe, show complex morphologies, host binary central stars, and are located at relatively high Galactic latitudes.

  6. 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

  7. Magnetic Measurements of Superconducting KxFe2-ySe2 Single Crystals Under High Pressure

    NASA Astrophysics Data System (ADS)

    Miyoshi, K.; Kondo, M.; Morishita, K.; Takeuchi, J.

    Measurements of DC magnetization for single crystal specimens of KxFe2-ySe2 both under hydrostatic and uniaxial pressure have been performed using liquid Ar and NaCl as pressure transmitting media to generate hydrostatic and nearly uniaxial pressure, respectively. It has been found that TC is pressure independent below 2 GPa but decreases rapidly above 3 GPa under hydrostatic pressure, indicating that the bulk superconductivity disappears above 6 GPa. We have also observed a very weak diamagnetic response below ∽10 K for P≥6 GPa, suggesting that non-bulk superconductivity survives even under high pressure. On the other hand, TC is found to decrease rapidly above 1.5 GPa by the application of uniaxial pressure along c-axis, indicating that the lattice compression along c-axis suppresses the superconductivity more effectively. This suggests that c-axis lattice constant is an important factor to determine TC in KxFe2-ySe2.

  8. Acrylic-based 1×2 Y-Branch POF coupler with high index contrast waveguide taper

    NASA Astrophysics Data System (ADS)

    Ehsan, A. A.; Abd Rahman, M. K.

    2010-12-01

    An acrylic-based 1x2 Y-Branch POF coupler consists of input POF waveguide, a middle high index contrast waveguide taper and output POF waveguides has been developed. The optical device is based on a 1x2 Y-branch coupler design with a middle high index contrast waveguide taper. Device modeling has been performed using non-sequential ray tracing with an insertion loss of 4.68 dB and coupling ratio of 50:50. Low cost acrylic material has been used for the device substrate. This middle waveguide taper region is constructed on the acrylic block itself without using any additional optical waveguiding medium injected into the engraved taper region. Fabrication of the devices is done by producing the device structures on an acrylic block using high speed CNC machining tool. Input and output POF fibers are inserted in to this device structure in such a way that they are passively aligned to the middle waveguide taper structure. The measured insertion loss is 7.5 dB and with a splitting ratio of 50:50.

  9. Acrylic-based 1×2 Y-Branch POF coupler with high index contrast waveguide taper

    NASA Astrophysics Data System (ADS)

    Ehsan, A. A.; Abd Rahman, M. K.

    2011-01-01

    An acrylic-based 1x2 Y-Branch POF coupler consists of input POF waveguide, a middle high index contrast waveguide taper and output POF waveguides has been developed. The optical device is based on a 1x2 Y-branch coupler design with a middle high index contrast waveguide taper. Device modeling has been performed using non-sequential ray tracing with an insertion loss of 4.68 dB and coupling ratio of 50:50. Low cost acrylic material has been used for the device substrate. This middle waveguide taper region is constructed on the acrylic block itself without using any additional optical waveguiding medium injected into the engraved taper region. Fabrication of the devices is done by producing the device structures on an acrylic block using high speed CNC machining tool. Input and output POF fibers are inserted in to this device structure in such a way that they are passively aligned to the middle waveguide taper structure. The measured insertion loss is 7.5 dB and with a splitting ratio of 50:50.

  10. Metabotropic P2Y1 receptor signalling mediates astrocytic hyperactivity in vivo in an Alzheimer's disease mouse model.

    PubMed

    Delekate, Andrea; Füchtemeier, Martina; Schumacher, Toni; Ulbrich, Cordula; Foddis, Marco; Petzold, Gabor C

    2014-11-19

    Astrocytic network alterations have been reported in Alzheimer's disease (AD), but the underlying pathways have remained undefined. Here we measure astrocytic calcium, cerebral blood flow and amyloid-β plaques in vivo in a mouse model of AD using multiphoton microscopy. We find that astrocytic hyperactivity, consisting of single-cell transients and calcium waves, is most pronounced in reactive astrogliosis around plaques and is sometimes associated with local blood flow changes. We show that astroglial hyperactivity is reduced after P2 purinoreceptor blockade or nucleotide release through connexin hemichannels, but is augmented by increasing cortical ADP concentration. P2X receptor blockade has no effect, but inhibition of P2Y1 receptors, which are strongly expressed by reactive astrocytes surrounding plaques, completely normalizes astrocytic hyperactivity. Our data suggest that astroglial network dysfunction is mediated by purinergic signalling in reactive astrocytes, and that intervention aimed at P2Y1 receptors or hemichannel-mediated nucleotide release may help ameliorate network dysfunction in AD.

  11. 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.

  12. Tailoring the magnetoelectric coupling in the Co2Y type hexaferrite single crystals by systematic doping control

    NASA Astrophysics Data System (ADS)

    Shin, Kwangwoo; Park, Chang Bae; Chun, Sae Hwan; Kim, Kee Hoon

    2015-03-01

    Hexagonal ferrites have shown gigantic magnetoelectric (ME) coupling in a broad temperature range including room temperature, which draws great interests due to their rich physics and various application potential. Here, we report the variations of the ME coupling and electrical phase boundary in the Sr and Al doped Co2Y type single crystal. As the doping ratio of Sr and Al ions increased, not only the transition temperature of the heliconical spin ordering increased up to 430 K, but also the ferroelectric phase boundary became closer to the zero magnetic field. These two main effects lead us to observe the large direct and converse ME effects at room temperature and near zero magnetic field. In particular, in an optimally doped sample, the ME susceptibility reaches to 28,000 ps/m at 10 K and the magnetization direction could be reversed by an external electric field even at 250 K without any bias magnetic field. These results clearly show that the Co2Y type hexaferrite is a promising material system that might realize the magnetization reversal even at room temperature.

  13. 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.

  14. 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

  15. Doping dependence of correlation effects in K1 - x Fe2 - y Se2 superconductors: LDA' + DMFT investigation

    NASA Astrophysics Data System (ADS)

    Nekrasov, I. A.; Pavlov, N. S.; Sadovskii, M. V.

    2013-11-01

    We present a detailed LDA' + DMFT investigation of the doping dependence of correlation effects in the novel K1 - x Fe2 - y Se2 superconductor. Calculations are performed at four different hole doping levels, starting from a hypothetical stoichiometric composition with the total number of electrons equal to 29 per unit cell through 28 and 27.2 electrons toward the case of 26.52, which corresponds to the chemical composition K0.76Fe1.72Se2 studied in recent ARPES experiments. In the general case, the increase in hole doping leads to quasiparticle bands in a wide energy window ±2 eV around the Fermi level becoming more broadened by lifetime effects, while correlation-induced compression of Fe-3 d LDA' bandwidths stays almost the same, of the order of 1.3 for all hole concentrations. However, close to the Fermi level, the situation is more complicated. In the energy interval from -1.0 eV to 0.4 eV, the bare Fe-3 d LDA' bands are compressed by significantly larger renormalization factors up to 5 with increased hole doping, while the value of Coulomb interaction remains the same. This fact manifests the increase in correlation effects with hole doping in the K1 - x Fe2 - y Se2 system. Moreover, in contrast to typical pnictides, K1 - x Fe2 - y Se2 does not have well-defined quasiparticle bands on the Fermi levels, but has a "pseudogap"-like dark region instead. We also find that with the growth of hole doping, Fe-3 d orbitals of various symmetries are affected by correlations differently in different parts of the Brillouin zone. To illustrate this, we determine the quasiparticle mass renormalization factors and energy shifts that transform the bare Fe-3 d LDA' bands of various symmetries into LDA' + DMFT quasiparticle bands. These renormalization factors effectively mimic more complicated energy-dependent self-energy effects and can be used to analyze the available ARPES data.

  16. 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.

  17. Theoretical study of structure and production of F19Λ as a gateway to sd-shell hypernuclei

    NASA Astrophysics Data System (ADS)

    Umeya, Atsushi; Motoba, Toshio

    2016-10-01

    Energy level structures of the typical light sd-shell hypernucleus F19Λ, together with 18F, have been studied in detail with the multi-configuration shell model. Both positive-parity and negative-parity nuclear core excitations are fully taken into account by removing the spurious center-of-mass excitation effects. Corresponding to the J-PARC proposal of the 19F (K- ,π- γ) F19Λ experiment, the production cross sections have been estimated extensively, including the angular distributions. Starting with the elementary amplitudes for the K- n → Λπ- process, the microscopic DWIA calculations at high energy kaon momenta up to 1.8 GeV / c have been carried out for the first time. The calculated wave functions are also used to estimate the electromagnetic transition probabilities for both 18F and F19Λ. The detailed γ-decay schemes are presented and discussed.

  18. 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).

  19. 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

  20. 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

  1. 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.

  2. Expression and purification of a single-chain Type IV restriction enzyme Eco94GmrSD and determination of its substrate preference.

    PubMed

    He, Xinyi; Hull, Victoria; Thomas, Julie A; Fu, Xiaoqing; Gidwani, Sonal; Gupta, Yogesh K; Black, Lindsay W; Xu, Shuang-yong

    2015-05-19

    The first reported Type IV restriction endonuclease (REase) GmrSD consists of GmrS and GmrD subunits. In most bacteria, however, the gmrS and gmrD genes are fused together to encode a single-chain protein. The fused coding sequence for ECSTEC94C_1402 from E. coli strain STEC_94C was expressed in T7 Express. The protein designated as Eco94GmrSD displays modification-dependent ATP-stimulated REase activity on T4 DNA with glucosyl-5-hydroxymethyl-cytosines (glc-5hmC) and T4gt DNA with 5-hydroxymethyl-cytosines (5hmC). A C-terminal 6xHis-tagged protein was purified by two-column chromatography. The enzyme is active in Mg(2+) and Mn(2+) buffer. It prefers to cleave large glc-5hmC- or 5hmC-modified DNA. In phage restriction assays, Eco94GmrSD weakly restricted T4 and T4gt, whereas T4 IPI*-deficient phage (Δip1) were restricted more than 10(6)-fold, consistent with IPI* protection of E. coli DH10B from lethal expression of the closely homologous E. coli CT596 GmrSD. Eco94GmrSD is proposed to belong to the His-Asn-His (HNH)-nuclease family by the identification of a putative C-terminal REase catalytic site D507-H508-N522. Supporting this, GmrSD variants D507A, H508A, and N522A displayed no endonuclease activity. The presence of a large number of fused GmrSD homologs suggests that GmrSD is an effective phage exclusion protein that provides a mechanism to thwart T-even phage infection.

  3. 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

  4. Inhibition of UDP/P2Y6 purinergic signaling prevents phagocytosis of viable neurons by activated microglia in vitro and in vivo.

    PubMed

    Neher, Jonas J; Neniskyte, Urte; Hornik, Tamara; Brown, Guy C

    2014-09-01

    Microglia activated through Toll-like receptor (TLR)-2 or -4 can cause neuronal death by phagocytosing otherwise-viable neurons-a form of cell death called "phagoptosis." UDP release from neurons has been shown to provoke microglial phagocytosis of neurons via microglial P2Y6 receptors, but whether inhibition of this process affects neuronal survival is unknown. We tested here whether inhibition of P2Y6 signaling could prevent neuronal death in inflammatory conditions, and whether UDP signaling can induce phagoptosis of stressed but viable neurons. We find that delayed neuronal loss and death in mixed neuronal/glial cultures induced by the TLR ligands lipopolysaccharide (LPS) or lipoteichoic acid was prevented by: apyrase (to degrade nucleotides), Reactive Blue 2 (to inhibit purinergic signaling), or MRS2578 (to specifically block P2Y6 receptors). In each case, inflammatory activation of microglia was not affected, and the rescued neurons remained viable for at least 7 days. Blocking P2Y6 receptors with MRS2578 also prevented phagoptosis of neurons induced by 250 nM amyloid beta 1-42, 5 μM peroxynitrite, or 50 μM 3-morpholinosydnonimine (which releases reactive oxygen and nitrogen species). Furthermore, the P2Y6 receptor agonist UDP by itself was sufficient to stimulate microglial phagocytosis and to induce rapid neuronal loss that was prevented by eliminating microglia or inhibiting phagocytosis. In vivo, injection of LPS into rat striatum induced microglial activation and delayed neuronal loss and blocking P2Y6 receptors with MRS2578 prevented this neuronal loss. Thus, blocking UDP/P2Y6 signaling is sufficient to prevent neuronal loss and death induced by a wide range of stimuli that activate microglial phagocytosis of neurons.

  5. 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

  6. P2Y1 receptors expressed by C1 neurons determine peripheral chemoreceptor modulation of breathing, sympathetic activity, and blood pressure.

    PubMed

    Wenker, Ian C; Sobrinho, Cleyton R; Takakura, Ana C; Mulkey, Daniel K; Moreira, Thiago S

    2013-08-01

    Catecholaminergic C1 cells of the rostral ventrolateral medulla (RVLM) are key determinants of the sympathoexcitatory response to peripheral chemoreceptor activation. Overactivation of this reflex is thought to contribute to increased sympathetic activity and hypertension; however, molecular mechanisms linking peripheral chemoreceptor drive to hypertension remain poorly understood. We have recently determined that activation of P2Y1 receptors in the RVLM mimicked effects of peripheral chemoreceptor activation. Therefore, we hypothesize that P2Y1 receptors regulate peripheral chemoreceptor drive in this region. Here, we determine whether P2Y1 receptors are expressed by C1 neurons in the RVLM and contribute to peripheral chemoreceptor control of breathing, sympathetic activity, and blood pressure. We found that injection of a specific P2Y1 receptor agonist (MRS2365) into the RVLM of anesthetized adult rats increased phrenic nerve activity (≈55%), sympathetic nerve activity (38 ± 6%), and blood pressure (23 ± 1 mm Hg), whereas application of a specific P2Y1 receptor antagonist (MRS2179) decreased peripheral chemoreceptor-mediated activation of phrenic nerve activity, sympathetic nerve activity, and blood pressure. To establish that P2Y1 receptors are expressed by C1 cells, we determine in the brain slice preparation using cell-attached recording techniques that cells responsive to MRS2365 are immunoreactive for tyrosine hydroxylase (a marker of C1 cells), and we determine in vivo that C1-lesioned animals do not respond to RVLM injection of MRS2365. These data identify P2Y1 receptors as key determinants of peripheral chemoreceptor regulation of breathing, sympathetic nerve activity, and blood pressure.

  7. Purinergic P2Y2 receptors mediate rapid Ca(2+) mobilization, membrane hyperpolarization and nitric oxide production in human vascular endothelial cells.

    PubMed

    Raqeeb, Abdul; Sheng, Jianzhong; Ao, Ni; Braun, Andrew P

    2011-04-01

    In blood vessels, stimulation of the vascular endothelium by the Ca(2+)-mobilizing agonist ATP initiates a number of cellular events that cause relaxation of the adjacent smooth muscle layer. Although vascular endothelial cells are reported to express several subtypes of purinergic P2Y and P2X receptors, the major isoform(s) responsible for the ATP-induced generation of vasorelaxant signals in human endothelium has not been well characterized. To address this issue, ATP-evoked changes in cytosolic Ca(2+), membrane potential and acute nitric oxide production were measured in isolated human umbilical vein endothelial cells (HUVECs) and profiled using established P2X and P2Y receptor probes. Whereas selective P2X agonist (i.e. α,β-methyl ATP) and antagonists (i.e. TNP-ATP and PPADS) could neither mimic nor block the observed ATP-evoked cellular responses, the specific P2Y receptor agonist UTP functionally reproduced all the ATP-stimulated effects. Furthermore, both ATP and UTP induced intracellular Ca(2+) mobilization with comparable EC(50) values (i.e. 1-3μM). Collectively, these functional and pharmacological profiles strongly suggest that ATP acts primarily via a P2Y2 receptor sub-type in human endothelial cells. In support, P2Y2 receptor mRNA and protein were readily detected in isolated HUVECs, and siRNA-mediated knockdown of endogenous P2Y2 receptor protein significantly blunted the cytosolic Ca(2+) elevations in response to ATP and UTP, but did not affect the histamine-evoked response. In summary, these results identify the P2Y2 isoform as the major purinergic receptor in human vascular endothelial cells that mediates the cellular actions of ATP linked to vasorelaxation.

  8. P2Y2 nucleotide receptor activation up-regulates vascular cell adhesion molecule-1 [corrected] expression and enhances lymphocyte adherence to a human submandibular gland cell line.

    PubMed

    Baker, Olga J; Camden, Jean M; Rome, Danny E; Seye, Cheikh I; Weisman, Gary A

    2008-01-01

    Sjögren's syndrome (SS) is a chronic inflammatory autoimmune disease that causes salivary and lacrimal gland tissue destruction resulting in impaired secretory function. Although lymphocytic infiltration of salivary epithelium is associated with SS, the mechanisms involved have not been adequately elucidated. Our previous studies have shown that the G protein-coupled P2Y2 nucleotide receptor (P2Y2R) is up-regulated in response to damage or stress of salivary gland epithelium, and in salivary glands of the NOD.B10 mouse model of SS-like autoimmune exocrinopathy. Additionally, we have shown that P2Y2R activation up-regulates vascular cell adhesion molecule-1 (VCAM-1) expression in endothelial cells leading to the binding of monocytes. The present study demonstrates that activation of the P2Y2R in dispersed cell aggregates from rat submandibular gland (SMG) and in human submandibular gland ductal cells (HSG) up-regulates the expression of VCAM-1. Furthermore, P2Y2R activation mediated the up-regulation of VCAM-1 expression in HSG cells leading to increased adherence of lymphocytic cells. Inhibitors of EGFR phosphorylation and metalloprotease activity abolished P2Y2R-mediated VCAM-1 expression and decreased lymphocyte binding to HSG cells. Moreover, silencing of EGFR expression abolished UTP-induced VCAM-1 up-regulation in HSG cells. These results suggest that P2Y2R activation in salivary gland cells increases the EGFR-dependent expression of VCAM-1 and the binding of lymphocytes, a pathway relevant to inflammation associated with SS.

  9. The P2Y2 nucleotide receptor mediates UTP-induced vascular cell adhesion molecule-1 expression in coronary artery endothelial cells.

    PubMed

    Seye, Cheikh I; Yu, Ningpu; Jain, Renu; Kong, Qiongman; Minor, Tess; Newton, Jessica; Erb, Laurie; González, Fernando A; Weisman, Gary A

    2003-07-01

    P2Y2 receptor up-regulation and activation induces intimal hyperplasia and monocyte/macrophage infiltration in the collared rabbit carotid artery model of vascular injury, suggesting a potential role for P2Y2 receptors in monocyte recruitment by vascular endothelium. In this study, we addressed the hypothesis that activation of P2Y2 receptors by extracellular nucleotides modulates the expression of adhesion molecules on vascular endothelial cells that are important for monocyte recruitment. Results indicated that the equipotent P2Y2 receptor agonists UTP or ATP (1-100 microm) stimulated the expression of vascular cell adhesion molecule-1 (VCAM-1) in human coronary artery endothelial cells (HCAEC) in a time- and dose-dependent manner. P2Y2 antisense oligonucleotides inhibited VCAM-1 expression induced by UTP but not by tumor necrosis factor-alpha. Furthermore, UTP induced VCAM-1 expression in human 1321N1 astrocytoma cell transfectants expressing the recombinant P2Y2 receptor, whereas vector-transfected control cells did not respond to UTP. The effect of UTP on VCAM-1 expression in HCAEC was prevented by depletion of intracellular calcium stores with thapsigargin or by inhibition of p38 mitogen-activated protein kinase or Rho kinase, but was not affected by inhibitors of the mitogen-activated protein/extracellular signal-regulated kinase pathway (i.e. MEK1/2). Consistent with a role for VCAM-1 in the recruitment of monocytes, UTP or ATP increased the adherence of monocytic U937 cells to HCAEC, an effect that was inhibited by anti-VCAM-1 antibodies. These findings suggest a novel role for the P2Y2 receptor in the p38- and Rho kinase-dependent expression of VCAM-1 that mediates the recruitment of monocytes by vascular endothelium associated with the development of atherosclerosis.

  10. P2Y2 Nucleotide Receptor Activation Up-regulates Vascular Cell Adhesion Molecular-1 Expression and Enhances Lymphocyte Adherence to a Human Submandibular Gland Cell Line

    PubMed Central

    Baker, Olga J.; Camden, Jean M.; Rome, Danny E.; Seye, Cheikh I.; Weisman, Gary A.

    2007-01-01

    Sjögren’s syndrome (SS) is a chronic inflammatory autoimmune disease that causes salivary and lacrimal gland tissue destruction resulting in impaired secretory function. Although lymphocytic infiltration of salivary epithelium is associated with SS, the mechanisms involved have not been adequately elucidated. Our previous studies have shown that the G protein-coupled P2Y2 nucleotide receptor (P2Y2R) is up-regulated in response to damage or stress of salivary gland epithelium, and in salivary glands of the NOD.B10 mouse model of SS-like autoimmune exocrinopathy. Additionally, we have shown that P2Y2R activation up-regulates vascular cell adhesion molecule-1 (VCAM-1) expression in endothelial cells leading to the binding of monocytes. The present study demonstrates that activation of the P2Y2R in dispersed cell aggregates from rat submandibular gland (SMG) and in human submandibular gland ductal cells (HSG) up-regulates the expression of VCAM-1. Furthermore, P2Y2R activation mediated the up-regulation of VCAM-1 expression in HSG cells leading to increased adherence of lymphocytic cells. Inhibitors of EGFR phosphorylation and metalloprotease activity abolished P2Y2R-mediated VCAM-1 expression and decreased lymphocyte binding to HSG cells. Moreover, silencing of EGFR expression abolished UTP-induced VCAM-1 up-regulation in HSG cells. These results suggest that P2Y2R activation in salivary gland cells increases the EGFR-dependent expression of VCAM-1 and the binding of lymphocytes, a pathway relevant to inflammation associated with SS. PMID:17599409

  11. 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.

  12. Dietary Na+ inhibits the open probability of the epithelial sodium channel in the kidney by enhancing apical P2Y2-receptor tone.

    PubMed

    Pochynyuk, Oleh; Rieg, Timo; Bugaj, Vladislav; Schroth, Jana; Fridman, Alla; Boss, Gerry R; Insel, Paul A; Stockand, James D; Vallon, Volker

    2010-06-01

    Apical release of ATP and UTP can activate P2Y(2) receptors in the aldosterone-sensitive distal nephron (ASDN) and inhibit the open probability (P(o)) of the epithelial sodium channel (ENaC). Little is known, however, about the regulation and physiological relevance of this system. Patch-clamp studies in freshly isolated ASDN provide evidence that increased dietary Na(+) intake in wild-type mice lowers ENaC P(o), consistent with a contribution to Na(+) homeostasis, and is associated with increased urinary concentrations of UTP and the ATP hydrolytic product, ADP. Genetic deletion of P2Y(2) receptors in mice (P2Y(2)(-/-); littermates to wild-type mice) or inhibition of apical P2Y-receptor activation in wild-type mice prevents dietary Na(+)-induced lowering of ENaC P(o). Although they lack suppression of ENaC P(o) by dietary NaCl, P2Y(2)(-/-) mice do not exhibit NaCl-sensitive blood pressure, perhaps as a consequence of compensatory down-regulation of aldosterone levels. Consistent with this hypothesis, clamping mineralocorticoid activity at high levels unmasks greater ENaC activity and NaCl sensitivity of blood pressure in P2Y(2)(-/-) mice. The studies indicate a key role of the apical ATP/UTP-P2Y(2)-receptor system in the inhibition of ENaC P(o) in the ASDN in response to an increase in Na(+) intake, thereby contributing to NaCl homeostasis and blood pressure regulation. PMID:20097874

  13. 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.

  14. 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

  15. 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.

  16. Ectopic expression of Capsicum-specific cell wall protein Capsicum annuum senescence-delaying 1 (CaSD1) delays senescence and induces trichome formation in Nicotiana benthamiana.

    PubMed

    Seo, Eunyoung; Yeom, Seon-In; Jo, Sunghwan; Jeong, Heejin; Kang, Byoung-Cheorl; Choi, Doil

    2012-04-01

    Secreted proteins are known to have multiple roles in plant development, metabolism, and stress response. In a previous study to understand the roles of secreted proteins, Capsicum annuum secreted proteins (CaS) were isolated by yeast secretion trap. Among the secreted proteins, we further characterized Capsicum annuum senescence-delaying 1 (CaSD1), a gene encoding a novel secreted protein that is present only in the genus Capsicum. The deduced CaSD1 contains multiple repeats of the amino acid sequence KPPIHNHKPTDYDRS. Interestingly, the number of repeats varied among cultivars and species in the Capsicum genus. CaSD1 is constitutively expressed in roots, and Agrobacterium-mediated transient overexpression of CaSD1 in Nicotiana benthamiana leaves resulted in delayed senescence with a dramatically increased number of trichomes and enlarged epidermal cells. Furthermore, senescence- and cell division-related genes were differentially regulated by CaSD1-overexpressing plants. These observations imply that the pepper-specific cell wall protein CaSD1 plays roles in plant growth and development by regulating cell division and differentiation.

  17. 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

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

    PubMed

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

    2015-06-01

    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 33258 uptake in 20-70% of cells from seven cervical cancer cell lines, it stimulated uptake in less than 8% of cervical epithelial cells obtained from the normal transformation zone and ectocervix tissue of 11 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.

  19. 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

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

    NASA Astrophysics Data System (ADS)

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

    2015-11-01

    We present 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 the superconducting phase (stripe phase) are connected with the arrangement of K, Fe, and Co atoms. Semiconducting spin glass is found in proximity to the superconducting state, persisting for large Co concentrations. At high Co concentrations a ferromagnetic metallic state emerges above the spin glass. This is coincident with changes of the unit cell and arrangement and connectivity of the stripe conducting phase.

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

    DOE PAGES

    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

  2. Study on the phase evolution of (Pb,Cu)Sr2(Y,Ca)Cu2Oz (z 7)

    NASA Astrophysics Data System (ADS)

    Maeda, T.; Taniwaki, M.

    2006-09-01

    The formation process of (Pb(1+x )/2Cu(1-x )/2)Sr2(Y1-x Cax )Cu2Oz is investigated by means of X-ray diffractometory (XRD), thermal analysis and scanning electron microscopy for nominal compositions of x = 00.5. It is shown by XRD measurement that nearly single-phase samples are obtained at x = 00.4 by firing at 1000 °C in air for only 1 h. In the heating step, the existence of partial melting state slightly below the firing temperature is clearly observed in the results of differential thermal analysis. It is concluded that this causes the extremely rapid formation of this compound.

  3. 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

  4. 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.

  5. 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.

  6. Down-regulation of miR-135b in colon adenocarcinoma induced by a TGF-β receptor I kinase inhibitor (SD-208)

    PubMed Central

    Akbari, Abolfazl; Ghahremani, Mohammad Hossein; Mobini, Gholam Reza; Abastabar, Mahdi; Akhtari, Javad; Bolhassani, Manzar; Heidari, Mansour

    2015-01-01

    Objective(s): Transforming growth factor-β (TGF-β) is involved in colorectal cancer (CRC). The SD-208 acts as an anti-cancer agent in different malignancies via TGF-β signaling. This work aims to show the effect of manipulation of TGF-β signaling on some miRNAs implicated in CRC. Materials and Methods: We investigated the effects of SD-208 on SW-48, a colon adenocarcinoma cell line. The cell line was treated with 0.5, 1 and 2 μM concentrations of SD-208. Then, the xenograft model of colon cancer was established by subcutaneous inoculation of SW-48 cell line into the nude mice. The animals were treated with SD-208 for three weeks. A quantitative real-time PCR was carried out for expression level analysis of selected oncogenic (miR-21, 31, 20a and 135b) and suppressor-miRNAs (let7-g, miR-133b, 145 and 200c). Data were analyzed using the 2-∆∆CT method through student’s t-test via the GraphPad Prism software. Results: Our results revealed that SD-208 could significantly down-regulate the expression of one key onco-miRNA, miR-135b, in either SW-48 colon cells (P=0.006) or tumors orthotopically implanted in nude mice (P=0.018). Our in silico study also predicted that SD-208 could modulate the expression of potential downstream tumor suppressor targets of the miR135b. Conclusion: Our data provide novel evidence that anticancer effects of SD-208 (and likely other TGF-β inhibitors) may be owing to their ability to regulate miRNAs expression. PMID:26523217

  7. 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

  8. 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

    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

  9. 4-Benzothiazole-7-hydroxyindolinyl diaryl ureas are potent P2Y1 antagonists with favorable pharmacokinetics: low clearance and small volume of distribution.

    PubMed

    Qiao, Jennifer X; Wang, Tammy C; Hiebert, Sheldon; Hu, Carol H; Schumacher, William A; Spronk, Steven A; Clark, Charles G; Han, Ying; Hua, Ji; Price, Laura A; Shen, Hong; Chacko, Silvi A; Everlof, Gerry; Bostwick, Jeffrey S; Steinbacher, Thomas E; Li, Yi-Xin; Huang, Christine S; Seiffert, Dietmar A; Rehfuss, Robert; Wexler, Ruth R; Lam, Patrick Y S

    2014-10-01

    Current antithrombotic discovery efforts target compounds that are highly efficacious in thrombus reduction with less bleeding liability than the standard of care. Preclinical data suggest that P2Y1 antagonists may have lower bleeding liabilities than P2Y12 antagonists while providing similar antithrombotic efficacy. This article describes our continuous SAR efforts in a series of 7-hydroxyindolinyl diaryl ureas. When dosed orally, 4-trifluoromethyl-7-hydroxy-3,3-dimethylindolinyl analogue 4 was highly efficacious in a model of arterial thrombosis in rats with limited bleeding. The chemically labile CF3 group in 4 was then transformed to various groups via a novel one-step synthesis, yielding a series of potent P2Y1 antagonists. Among them, the 4-benzothiazole-substituted indolines had desirable PK properties in rats, specifically, low clearance and small volume of distribution. In addition, compound 40 had high i.v. exposure and modest bioavailability, giving it the best overall profile. PMID:24989964

  10. CONDENSED MATTER: ELECTRONIC STRUCTURE, ELECTRICAL, MAGNETIC, AND OPTICAL PROPERTIES Tunneling Conductance in dx2 - y2 + idxy Mixed Wave Superconductor Graphene Junctions

    NASA Astrophysics Data System (ADS)

    Li, Xiao-Wei

    2010-12-01

    Using the extended Blonder—Tinkham—Klapwijk formalism, we investigate the conductance spectra of normal metal/dx2 - y2 + idxy mixed wave superconductor graphene junctions. It is found that the conductance spectra vary strongly with the orientation of the gap and the amplitude ratio (Δ1/Δ0 of two components for dx2 - y2 + idxy mixed wave. The zero bias conductance is nearly 2 and the conductance peak vanishes in doped graphene for α = 0 and Δ1/Δ0 = 1. The conductance increases with increasing the amplitude ratio of two components for α = π/4 and Δ1/Δ0 = 1. The ZBCP becomes observable wide with 1 < EF/Δ0 < 100 for α = π/4 and Δ1/Δ0 = 1. This property is different from that in normal metal/dx2 - y2 wave superconductor graphene junctions.

  11. 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.

  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. Gene-by-environment effect of house dust mite on purinergic receptor P2Y12 (P2RY12) and lung function in children with asthma

    PubMed Central

    Bunyavanich, Supinda; Boyce, Joshua A.; Raby, Benjamin A.; Weiss, Scott T.

    2012-01-01

    Background Distinct receptors likely exist for leukotriene(LT)E4, a potent mediator of airway inflammation. Purinergic receptor P2Y12 is needed for LTE4-induced airways inflammation, and P2Y12 antagonism attenuates house dust mite-induced pulmonary eosinophilia in mice. Although experimental data support a role for P2Y12 in airway inflammation, its role in human asthma has never been studied. Objective To test for association between variants in the P2Y12 gene (P2RY12) and lung function in human subjects with asthma, and to examine for gene-by-environment interaction with house dust mite exposure. Methods 19 single nucleotide polymorphisms (SNPs) in P2RY12 were genotyped in 422 children with asthma and their parents (n=1266). Using family-based methods, we tested for associations between these SNPs and five lung function measures. We performed haplotype association analyses and tested for gene-by-environment interactions using house dust mite exposure. We used the false discovery rate to account for multiple comparisons. Results Five SNPs in P2RY12 were associated with multiple lung function measures (P values 0.006–0.025). Haplotypes in P2RY12 were also associated with lung function (P values 0.0055–0.046). House dust mite exposure modulated associations between P2RY12 and lung function, with minor allele homozygotes exposed to house dust mite demonstrating worse lung function than those unexposed (significant interaction P values 0.0028–0.040). Conclusions and clinical relevance P2RY12 variants were associated with lung function in a large family-based asthma cohort. House dust mite exposure caused significant gene-by-environment effects. Our findings add the first human evidence to experimental data supporting a role for P2Y12 in lung function. P2Y12 could represent a novel target for asthma treatment. PMID:22010907

  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. P2Y2 Receptor-mediated Lymphotoxin-α Secretion Regulates Intercellular Cell Adhesion Molecule-1 Expression in Vascular Smooth Muscle Cells*

    PubMed Central

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

    2012-01-01

    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 P2Y2 nucleotide receptor (P2Y2R) agonist UTP stimulates a strong and sustained release of LTA from WT but not P2Y2R−/− 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 P2Y2R/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 P2Y2R deficient in LTA secretion. These data suggest that P2Y2R 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

  16. 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.

  17. 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.

  18. 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.

  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.

  1. 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

  2. LDA'+DMFT investigation of electronic structure of K1 - x Fe2 - y Se2 superconductor

    NASA Astrophysics Data System (ADS)

    Nekrasov, I. A.; Pavlov, N. S.; Sadovskii, M. V.

    2013-03-01

    We investigate electronic structure of the new iron chalcogenide high temperature superconductor K1- x Fe2- y Se2 (hole doped case with x = 0.24, y = 0.28) in the normal phase using the novel LDA'+DMFT computational approach. We show that this iron chalcogenide is more correlated in a sense of bandwidth renormalization (energy scale compression by factor about 5 in the interval ±1.5 eV), than typical iron pnictides (compression factor about 2), though the Coulomb interaction strength is almost the same in both families. Our results for spectral densities are in general agreement with recent ARPES data on this system. It is found that all Fe-3 d( t 2 g ) bands crossing the Fermi level have equal renormalization, in contrast to some previous interpretations. Electronic states at the Fermi level are of predominantly xy symmetry. Also we show that LDA'+DMFT results are in better agreement with experimental spectral function maps, than the results of conventional LDA+DMFT. Finally we make predictions for photoemission spectra lineshape for K0.76Fe1.72Se2.

  3. Fermi surface evolution and checker-board block-spin antiferromagnetism in AxFe2-ySe2

    NASA Astrophysics Data System (ADS)

    Tai, Yuan-Yen; Zhu, Jian-Xin; Graf, Matthias J.; Ting, C. S.

    2012-10-01

    We develop an effective multiorbital mean-field t-J Hamiltonian with realistic tight-binding and exchange parameters to describe the electronic and magnetic structures of iron-selenide based superconductors AxFe2-ySe2 for iron vacancy doping in the range 0≤y≤0.4. The Fermi surface topology extracted from the spectral function of angle-resolved photoemission spectroscopy (ARPES) experiments is adequately accounted for by a tight-binding lattice model with random vacancy disorder. Since introducing iron vacancies breaks the lattice periodicity of the stochiometric compound, it greatly affects the electronic band structure. With changing vacancy concentration, the electronic band structure evolves, leading to a reconstruction of the Fermi surface topology. For intermediate doping levels, the realized stable electronic structure is a compromise between the solutions for the perfect lattice with y=0 and the vacancy stripe-ordered lattice with y=0.4, which results in a competition between vacancy random disorder and vacancy stripe order. A multiorbital hopping model is parameterized by comparing Fermi surface topologies to ARPES experiments, from which we construct a mean-field t-J lattice model to study the paramagnetic and antiferromagnetic (AFM) phases of K0.8Fe1.6Se2. In the AFM phase the calculated spin magnetization of the t-J model leads to a checker-board block-spin structure in good agreement with neutron scattering experiments and abinitio calculations.

  4. 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.

  5. 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.

  6. 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

  7. Emergence of superconductivity and magnetic ordering tuned by Fe-vacancy in alkali-metal Fe chalcogenides RbxFe2-ySe2

    NASA Astrophysics Data System (ADS)

    Kobayashi, Yoshiaki; Kototani, Shouhei; Itoh, Masayuki; Sato, Masatoshi

    2014-12-01

    Samples of RbxFe2-ySe2 exhibiting superconductivity [superconducting (SC) samples] undergo a phase-separation into two phases, a Fe-vacancy ordered phase with antiferromagnetic (AFM) transition at TN1~500 K (AFM1 phase) and a phase with little Fe- vacancy and SC transition at Tc~30 K (SC phase). The samples of RbxFe2-ySe2 exhibiting no SC behaviour (non-SC samples) are phase-separated into three phases, the AFM1 phase, another AFM phase with TN2 ~150 K (AFM2 phase), and a paramagnetic phase with no SC transitions (paramagnetic non-SC phase). In this paper, we present the experimental results of magnetic susceptibility, electrical resistivity, and NMR measurements on single crystals of RbxFe2-ySe2 to reveal physical properties of these co-existing phases in the SC and non-SC samples. The 87Rb and 77Se NMR spectra show that the Fe vacancy concentration is very small in the Fe planes of the SC phase, whereas the AFM2 and paramagnetic non-SC phases in non-SC samples have larger amount of Fe vacancies. The randomness induced by the Fe vacancy in the non-SC samples makes the AFM2 and paramagnetic non-SC phases insulating/semiconducting and magnetically active, resulting in the absence of the superconductivity in RbxFe2-ySe2.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. Identification of Potent, Selective P2Y-Purinoceptor Agonists: Structure–Activity Relationships for 2-Thioether Derivatives of Adenosine 5′-Triphosphate†

    PubMed Central

    Fischer, Bilha; Boyer, José L.; Hoyle, Charles H. V.; Ziganshin, Airat U.; Brizzolara, Antonia L.; Knight, Gillian E.; Zimmet, Jeffrey; Burnstock, Geoffrey; Harden, T. Kendall; Jacobson, Kenneth A.

    2012-01-01

    Study of P2-purinoceptor subtypes has been difficult due to the lack of potent and selective ligands. With the goal of developing high affinity P2-purinoceptor-selective agonists, we have synthesized a series of analogues of adenine nucleotides modified on the purine ring as chain-extended 2-thioethers or as N6-methyl-substituted compounds. Chemical functionality incorporated in the thioether moiety included cyanoalkyl, nitroaromatic, amino, thiol, cycloalkyl, n-alkyl, and olefinic groups. Apparent affinity of the compounds for P2Y-purinoceptors was established by measurement of P2Y-purinoceptor-promoted phospholipase C activity in turkey erythrocyte membranes and relaxation of carbachol-contracted smooth muscle in three different preparations (guinea pig taenia coil, rabbit aorta, and rabbit mesenteric artery). Activity at P2X-purinoceptors was established by measurement of contraction of rabbit saphenous artery and of the guinea pig vas deferens and urinary bladder. All 11 of the 2-thioethers of ATP stimulated the production of inositol phosphates with K0.5 values of 1.5–770 nM, with an (aminophenyl)ethyl derivative being most potent. Two adenosine diphosphate analogues were equipotent to the corresponding ATP analogues. Adenosine monophosphate analogues were full agonists, although generally 4 orders of magnitude less potent. ATP 2-thioethers displayed pD2 values in the range of 6–8 in smooth muscle assay systems for activity at P2Y-receptors. There was a significant correlation for the 2-thioether compounds between the pK0.5 values for inositol phosphate production and the pD2 values for relaxation mediated via the P2Y-purinoceptors in the guinea pig taenia coli, but not for the vascular P2Y-receptors or for the P2X-receptors. At P2X-receptors, no activity was observed in the rabbit saphenous artery, but variable degrees of activity were observed in the guinea pig vas deferens and bladder depending on distal substituents of the thioether moiety. N6-Methyl

  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. 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.

  17. P2Y2 receptor activation opens pannexin-1 channels in rat carotid body type II cells: potential role in amplifying the neurotransmitter ATP.

    PubMed

    Zhang, Min; Piskuric, Nikol A; Vollmer, Cathy; Nurse, Colin A

    2012-09-01

    Signal processing in the carotid body (CB) is initiated at receptor glomus (or type I) cells which depolarize and release the excitatory neurotransmitter ATP during chemoexcitation by hypoxia and acid hypercapnia. Glomus cell clusters (GCs) occur in intimate association with glia-like type II cells which express purinergic P2Y2 receptors (P2Y2Rs) but their function is unclear. Here we immunolocalize the gap junction-like protein channel pannexin-1 (Panx-1) in type II cells and show Panx-1 mRNA expression in the rat CB. As expected, type II cell activation within or near isolated GCs by P2Y2R agonists, ATP and UTP (100 μm), induced a rise in intracellular [Ca(2+)]. Moreover in perforated-patch whole cell recordings from type II cells, these agonists caused a prolonged depolarization and a concentration-dependent, delayed opening of non-selective ion channels that was prevented by Panx-1 blockers, carbenoxolone (5 μm) and 4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS; 10 μm). Because Panx-1 channels serve as conduits for ATP release, we hypothesized that paracrine, type II cell P2Y2R activation leads to ATP-induced ATP release. In proof-of-principle experiments we used co-cultured chemoafferent petrosal neurones (PNs), which express P2X2/3 purinoceptors, as sensitive biosensors of ATP released from type II cells. In several cases, UTP activation of type II cells within or near GCs led to depolarization or increased firing in nearby PNs, and the effect was reversibly abolished by the selective P2X2/3 receptor blocker, pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS; 10 μm). We propose that CB type II cells may function as ATP amplifiers during chemotransduction via paracrine activation of P2Y2Rs and Panx-1 channels.

  18. 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

  19. Identification of a Promising Drug Candidate for the Treatment of Type 2 Diabetes Based on a P2Y1 Receptor Agonist ¶

    PubMed Central

    Yelovitch, Shir; Barr, Haim M.; Camden, Jean; Weisman, Gary A; Shai, Ela; Varon, David; Fischer, Bilha

    2015-01-01

    The activation by ettracellular nucleotides of pancreatic P2Y receptors, particularly, the P2Y1R subtype, increases insulin secretion. Therefure, we developed analogues of the P2Y1R receptor agonist 2 MeS ADP, as potential antidiabetic drugs. Analogue 3A was found to be a potent P2Y1R agonist (EC50 = 0.038 μM vs 0.0025 μM for 2 MeS-ADP) showing no activity at P2Y21416Rs. Analogue 3A was stable at pH 1.4 (t½ = 7.3 h) and resistant to hydrolysis vs 2-MeS ADP by alkaline phosphatase (t½ = 6 vs 4.5 h), human e-NPPl (4% vs 16% hydrolysis after 20 min), and hwnan blood serum (30% vs 50% hydrolysis after 24 h). Intravenous administration of 3A in naive rats decreased blood glucose from 155 mg/dL to normal values, ca. 87 mg/dL, unlike glibenclamide, leading to subnormal values (i.e., 63 mg/dL). Similar observations were made for strepto2otocin (STZ) treated and db+/db− mouse models. Furthermore, 3A inhibits platelet aggregation in vitro and elongates bleeding time in mice (iv administration of 30 mg of 3A/kg), increasing bleeding time to 16 vs 9 min for Prasugrel. Oral administration of30 mg/kg 3A to rats increased tail bleeding volwne, similar to aspirin. These findings suggest that 3A may be an effective treatment for type 2 diabetes by reducing both blood glucose levels and platelet aggregation. PMID:22873688

  20. Inhibition of PAR-4 and P2Y12 receptor-mediated platelet activation produces distinct hepatic pathologies in experimental xenobiotic-induced cholestatic liver disease.

    PubMed

    Joshi, Nikita; Kopec, Anna K; Ray, Jessica L; Luyendyk, James P

    2016-07-15

    Emerging evidence supports a protective effect of platelets in experimental cholestatic liver injury and cholangiofibrosis. Coagulation-mediated platelet activation has been shown to inhibit experimental chronic cholestatic liver necrosis and biliary fibrosis. This occurs through thrombin-mediated activation of protease activated receptor-4 (PAR-4) in mice. However, it is not known whether other pathways of platelet activation, such as adenosine diphosphate (ADP)-mediated receptor P2Y12 activation is also protective. We tested the hypothesis that inhibition of P2Y12-mediated platelet activation exacerbates hepatic injury and cholangiofibrosis, and examined the impact of P2Y12 inhibition in both the presence and absence of PAR-4. Treatment of wild-type mice with the P2Y12 receptor antagonist clopidogrel increased biliary hyperplasia and cholangiofibrosis in wild-type mice exposed to the xenobiotic alpha-naphthylisothiocyanate (ANIT) for 4 weeks compared to vehicle-treated mice exposed to ANIT. Interestingly, this effect of clopidogrel occurred without a corresponding increase in hepatocellular necrosis. Whereas biliary hyperplasia and cholangiofibrosis were increased in PAR-4(-/-) mice, clopidogrel treatment failed to further increase these pathologies in PAR-4(-/-) mice. The results indicate that inhibition of receptor P2Y12-mediated platelet activation exacerbates bile duct fibrosis in ANIT-exposed mice, independent of hepatocellular necrosis. Moreover, the lack of an added effect of clopidogrel administration on the exaggerated pathology in ANIT-exposed PAR-4(-/-) mice reinforces the prevailing importance of coagulation-mediated platelet activation in limiting this unique liver pathology. PMID:27475285

  1. 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…

  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. 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.

  4. GTC/OSIRIS Observations of RWT 152, a Case Study of a Planetary Nebula With an sdO Central Star

    NASA Astrophysics Data System (ADS)

    Aller, A.; Miranda, L. F.; Olguín, L.; Solano, E.; Ulla, A.

    2015-12-01

    RWT 152 is one of the few planetary nebula with an sdO central star. We present subarcsecond red tunable filter imaging and intermediate-resolution, long-slit spectroscopy of RWT 152, obtained with OSIRIS/GTC, which allow us to describe in detail its morphology and to obtain its physical conditions and chemical abundances.

  5. DIAGNOSTIC PERFORMANCE EVALUATION OF THE SD BIOLINE MALARIA ANTIGEN AG PF/PAN TEST (05FK60) IN A MALARIA ENDEMIC AREA OF SOUTHERN ETHIOPIA

    PubMed Central

    TADESSE, Endale; WORKALEMAHU, Bereket; SHIMELIS, Techalew

    2016-01-01

    SUMMARY Rapid diagnostic tests (RDTs) capable of detecting and differentiating Plasmodium species are needed in areas in which microscopy is unsuitable. This study was conducted to assess the diagnostic performance of the rapid test kit - SD BIOLINE Malaria Ag Pf/Pan(r) (05FK60) in an endemic area. Microscopy of Giemsa-stained blood films were performed to detect and estimate the Plasmodium density in malaria suspected patients. The performance of the SD BIOLINE Malaria Ag Pf/Pan test was evaluated using 272 Plasmodium-positive and 102 negative blood samples. The overall sensitivity of the SD BIOLINE Malaria Ag Pf/Pan test was 99.5% for P. falciparum and 92.6% for non-P. falciparum malaria infections. The respective specificity, PPV, and NPV of the test were 98.0, 98.4, and 99.0% for the diagnosis of P. falciparum, and 100.0 %, 100.0%, and 94.4% for non-P. falciparum species. The SD BIOLINE Malaria Ag Pf/Pan test showed an excellent performance in diagnosing Plasmodium infections in an endemic setting. Therefore, this point-of-care test could be used as an alternative to microscopy in places where P. falciparum is endemic and microscopy is unsuitable. PMID:27680164

  6. Reexamination of the difference in susceptibility to adjuvant-induced arthritis among LEW/Crj, Slc/Wistar/ST and Slc/SD rats.

    PubMed

    Banik, Ratan Kumar; Kasai, Masanori; Mizumura, Kazue

    2002-04-01

    The present investigations were performed to assess the differences among rat colonies commonly used for neurophysiological research regarding the development of complete Freund's adjuvant (CFA)-induced arthritis. Inflammatory signs including edema in the paw fluctuated remarkably among individual Wistar (Slc/Wistar/ST) and Sprague-Dawley (Slc/SD) rats, while the inflammatory signs of Lewis (LEW/Crj) rats appeared earlier and was severer and more consistent than Slc/Wistar/ST and Slc/SD rats. Edema in the hind paw developed in 100% of LEW/Crj rats with the lowest dose of CFA (0.6 mg/rat) used as compared with 64% of Slc/Wistar/ST (CFA 1 mg/rat) and 38% of Slc/SD rats (CFA 1.2 mg/rat). Retardation of weight gain was observed in Slc/Wistar/ST and Slc/SD rats in contrast to a severe weight decrease in inflamed LEW/Crj rats after the development of arthritis.

  7. 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...

  8. 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...

  9. 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.

  10. [Vitamin E prevents the toxic effect of benzo(a)pryene on reproductive system in male SD rats].

    PubMed

    Li, Wei; Dong, Ting; Yang, Kai; Wu, Mengyun; Tu, Baijie

    2015-11-01

    目的:探讨维生素E(vitamin E,VE)对苯并[a]芘(Benzo(a)pryene,B[a]P)诱导的雄性大鼠的生殖毒性的保护作用及其机制。方法:将60只28 d龄70~90 g Sprague Dawley (SD)大鼠随机分为空白、溶剂对照组、B[a]P组(5 mg/kg)及低(10 mg/kg)、中(50 mg/kg)、高(100 mg/kg)剂量VE联合B[a]P处理组共6组,每组各10只;连续灌胃30 d并检测各组精子质量、睾丸组织中超氧化物歧化酶(superoxide dismutase,SOD)和谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)活性、8-羟基脱氧鸟苷(8-hydroxy-2-deoxyguanosine,8-OHdG)和丙二醛(malondialdehyde,MDA)的含量;HE染色观察睾丸形态,采用彗星实验测定细胞DNA损伤程度。结果:与对照组相比,B[a]P组精子计数明显降低、精子畸形率、8-OHdG及MDA含量明显升高,SOD和GSH-Px活性显著下降(P<0.05);VE联合组SD大鼠的睾丸组织损伤程度明显减轻;上述各项氧化应激和DNA损伤指标也均明显改善;且随着VE剂量的增加,保护效应呈现明显的剂量-反应关系,差异均具有统计学意义(P<0.05)。结论:VE对B[a]P诱导的SD雄性大鼠生殖损害具有保护作用。.

  11. 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

  12. 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

  13. 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

  14. FUSE spectroscopy of the sdOB primary of the post common-envelope binary LB 3459(AA Doradus)

    NASA Astrophysics Data System (ADS)

    Fleig, J.; Rauch, T.; Werner, K.; Kruk, J. W.

    2008-12-01

    Context: LB 3459(AA Doradus) is an eclipsing, close, post common-envelope binary (PCEB) consisting of an sdOB primary star and an unseen secondary with an extraordinarily low mass (M2 ≈ 0.066 M_⊙) - formally a brown dwarf. A recent NLTE spectral analysis shows a discrepancy with the surface gravity, which is derived from analyses of radial-velocity and lightcurves. Aims: We aim at precisely determining of the photospheric parameters of the primary, especially of the surface gravity, and searching for weak metal lines in the far UV. Methods: We performed a detailed spectral analysis of the far-UV spectrum of LB 3459obtained with FUSE by means of state-of-the-art NLTE model-atmosphere techniques. Results: A strong contamination of the far-UV spectrum of LB 3459by interstellar line absorption hampers a precise determination of the photospheric properties of its primary star. Its effective temperature (T_eff = 42 kK) was confirmed by the evaluation of new ionization equilibria. For the first time, phosphorus and sulfur have been identified in the spectrum of LB 3459. Their photospheric abundances are solar and 0.01 times solar, respectively. From the C III λλ 1174-1177 Å multiplet, we can measure the rotational velocity v_rot = 35 ± 5 km s-1 of the primary of LB 3459and confirm that the rotation is bound. From a re-analysis of optical and UV spectra (analogue to Rauch 2000, A&A, 356, 665), we determine a slightly higher surface gravity log g = 5.3 ± 0.1 compared to Rauch (2000, log g = 5.2 ± 0.1). Conclusions: The rotational velocity of the primary of LB 3459is consistent with a bound rotation. The higher log g reduces the discrepancy in mass determination in comparison to analyses of radial-velocity and lightcurves. However, the problem is not completely solved. Based on observations made with the NASA-CNES-CSA Far Ultraviolet Spectroscopic Explorer. FUSE is operated for NASA by the Johns Hopkins University under NASA contract NAS5-32985.

  15. 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

  16. 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

  17. The qSD12 underlying gene promotes abscisic acid accumulation in early developing seeds to induce primary dormancy in rice.

    PubMed

    Gu, Xing-You; Liu, Tianlei; Feng, Jiuhuan; Suttle, Jeffrey C; Gibbons, James

    2010-05-01

    Seeds acquire primary dormancy during their development and the phytohormone abscisic acid (ABA) is known to play a role in inducing the dormancy. qSD12 is a major seed dormancy quantitative trait locus (QTL) identified from weedy rice. This research was conducted to identify qSD12 candidate genes, isolate the candidates from weedy rice, and determine the relation of the dormancy gene to ABA. A fine mapping experiment, followed by marker-assisted progeny testing for selected recombinants, narrowed down qSD12 to a genomic region of <75 kb, where there are nine predicted genes including a cluster of six transposon/retrotransposon protein genes and three putative (a PIL5, a hypothetic protein, and a bHLH transcription factor) genes based on the annotated Nipponbare genome sequence. The PIL5 and bHLH genes are more likely to be the QTL candidate genes. A bacterial artificial chromosome (BAC) library equivalent to 8-9 times of the haploid genome size was constructed for the weedy rice. One of the two BAC contigs developed from the library covers the PIL5 to bHLH interval. A pair of lines different only in the QTL-containing region of <200 kb was developed as isogenic lines for the qSD12 dormancy and non-dormancy alleles. The dormant line accumulated much higher ABA in 10-day developing seeds than the non-dormant line. In the QTL-containing region there is no predicted gene that has been assigned to ABA biosynthetic or metabolic pathways. Thus, it is concluded that the qSD12 underlying gene promotes ABA accumulation in early developing seeds to induce primary seed dormancy. PMID:19823935

  18. 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

  19. An X-Ray, Optical, and Radio Search for Supernova Remnants in the Nearby Sculptor Group Sd Galaxy NGC 7793

    NASA Astrophysics Data System (ADS)

    Pannuti, Thomas G.; Duric, Nebojsa; Lacey, Christina K.; Ferguson, Annette M. N.; Magnor, Marcus A.; Mendelowitz, Caylin

    2002-02-01

    This paper is the second in a series devoted to examining the multiwavelength properties of supernova remnants (SNRs) located in nearby galaxies. We consider here the resident SNRs in the nearby Sculptor group Sd galaxy NGC 7793. Using our own Very Large Array (VLA) radio observations at 6 and 20 cm, as well as archived ROSAT X-ray data, previously published optical results, and our own Hα image, we have searched for X-ray and radio counterparts to previously known optically identified SNRs and for new previously unidentified SNRs at these two wavelength regimes. Consistent with our prior results for NGC 300, only a tiny minority of the optically identified SNRs have been found at another wavelength. The most noteworthy source in our study is N7793-S26, which is the only SNR in this galaxy that is detected at all three wavelengths (X-ray, optical, and radio). It features a long (~450 pc) filamentary morphology that is clearly seen in both the optical and the radio images. N7793-S26's radio luminosity exceeds that of the Galactic SNR Cas A, and based on equipartition calculations we determine that an energy of at least 1052 ergs is required to maintain this source. Such a result argues for the source being created by multiple supernova explosions rather than by a single supernova event. A second optically identified SNR, N7793-S11, has detectable radio emission but no detectable X-ray emission. A radio-selected sample of candidate SNRs has also been prepared by searching for coincidences between nonthermal radio sources and regions of Hα emission in this galaxy. This search has produced five new candidate radio SNRs to be added to the 28 SNRs that have already been detected by optical methods. A complementary search for new candidate X-ray SNRs has also been conducted by searching for soft-spectrum sources (kT<1 keV) that are coincident with regions of Hα emission. That search has yielded a candidate X-ray SNR that is coincident with one (and possibly two) of the

  20. 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

  1. 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

  2. Potassium 2-(1-hydroxypentyl)-benzoate inhibits ADP-induced rat platelet aggregation through P2Y1-PLC signaling pathways.

    PubMed

    Yang, Hongyan; Xu, Shaofeng; Li, Jiang; Wang, Ling; Wang, Xiaoliang

    2015-09-01

    Potassium 2-(1-hydroxypenty1)-benzoate (dl-PHPB) is a new drug candidate for treatment of ischemic stroke with antiplatelet effect. In this study, we investigated the mechanisms of dl-PHPB in inhibiting platelet aggregation. The ADP-activated P2Y1-Gq-PLC and P2Y12-Gi-AC pathways were observed, respectively. Intravenous injection of dl-PHPB (1.3, 3.9, 12.9 mg/kg) significantly inhibited ADP-, collagen-, and arachidonic acid-induced rat platelet aggregation in a dose-dependent manner, and dl-PHPB had a relatively more potent inhibitory effect on ADP-induced rat platelet aggregation than other agonists. Dl-PHPB also showed a decreased expression of CD62P (a marker for platelet activation) mediated by ADP. Both dl-PHPB and ticlopidine (P2Y12 receptor antagonist) decreased cytoplasmic Ca(2+) concentration. But, dl-PHPB did not reverse the inhibition of PGE1-induced platelet cAMP formation by ADP, which was different from ticlopidine. Further, dl-PHPB instead of ticlopidine showed increasing phospholipase C-β phosphorylation (ser(1105)). The m-3M3FBS, a phospholipase C activator, attenuated the inhibitory effect of dl-PHPB on ADP-induced platelet aggregation and enhanced IP1 accumulation in rat platelets. Dl-PHPB decreased IP1 accumulation induced by ADP but had no effect on IP1 level enhanced by m-3M3FBS. Our results suggest that dl-PHPB has a potent antiplatelet effect, which is mainly through blockade of P2Y1 receptor-PLC-IP3 pathway and decreasing cytoplasmic calcium.

  3. 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.

  4. Resistive switching in the Au/Zr/ZrO2-Y2O3/TiN/Ti memristive devices deposited by magnetron sputtering

    NASA Astrophysics Data System (ADS)

    Gorshkov, O. N.; Mikhaylov, A. N.; Kasatkin, A. P.; Tikhov, S. V.; Filatov, D. O.; Pavlov, D. A.; Belov, A. I.; Koryazhkina, M. N.; Bobrov, A. I.; Malekhonova, N. V.; Gryaznov, E. G.; Antonov, I. N.; Shenina, M. E.

    2016-08-01

    Bipolar resistive switching phenomenon in the Au/Zr/ZrO2-Y2O3/TiN/Ti memristive devices deposited by magnetron sputtering has been studied. The structure of devices and electrical measurements data for the temperature range from 77 to 490 K are analyzed. The stable switching is demonstrated at room temperature, but the decrease in the resistive switching performance at elevated temperatures is observed.

  5. High Activity of Ce1-xNixO2-y for H2 Production through Ethanol Steam Reforming: Tuning Catalytic Performance through Metal↔Oxide Interactions

    SciTech Connect

    Rodriguez, J.A.; Zhou, G.; Barrio, L.; Agnoli, S.; Senanayake, S.D.; Evans, J.; Kubacka, A.; Estrella, M.; Hanson, J.C.; Martínez-Arias, A.; Fernández-García, M.

    2010-12-10

    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 O-H bonds in ethanol and water.

  6. 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

  7. 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

  8. Optical spectroscopy studies on FeTe1-xSex and AxFe2-ySe2 (A = K, Rb, Cs): A brief overview

    NASA Astrophysics Data System (ADS)

    Yuan, Rui-Hua; Wang, Nan-Lin

    2013-08-01

    In this short overview, we summarize the optical spectroscopy studies on iron selenide superconducting systems FeTe1-xSex and A-xFe2-ySe2. We elaborate that optical spectroscopy measurements yield fruitful information about the band structure evolution across the AFM phase transition temperature, the electronic correlation effect, the superconducting pairing energy gap, the condensed carrier density or penetration depth, the inhomogeneity and the nanoscale phase separation between superconductivity and antiferromagnetism in those systems.

  9. 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

  10. From ATP to AZD6140: the discovery of an orally active reversible P2Y12 receptor antagonist for the prevention of thrombosis.

    PubMed

    Springthorpe, Brian; Bailey, Andrew; Barton, Patrick; Birkinshaw, Timothy N; Bonnert, Roger V; Brown, Roger C; Chapman, David; Dixon, John; Guile, Simon D; Humphries, Robert G; Hunt, Simon F; Ince, Francis; Ingall, Anthony H; Kirk, Ian P; Leeson, Paul D; Leff, Paul; Lewis, Richard J; Martin, Barrie P; McGinnity, Dermot F; Mortimore, Michael P; Paine, Stuart W; Pairaudeau, Garry; Patel, Anil; Rigby, Aaron J; Riley, Robert J; Teobald, Barry J; Tomlinson, Wendy; Webborn, Peter J H; Willis, Paul A

    2007-11-01

    Starting from adenosine triphosphate (ATP), the identification of a novel series of P2Y(12) receptor antagonists and exploitation of their SAR is described. Modifications of the acidic side chain and the purine core and investigation of hydrophobic substituents led to a series of neutral molecules. The leading compound, 17 (AZD6140), is currently in a large phase III clinical trial for the treatment of acute coronary syndromes and prevention of thromboembolic clinical sequelae.

  11. 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.

  12. 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 observations showed that the size of SiO{sub 2}/Y{sub 2}O{sub 3}:Eu core-shell structure is in the range of 140-180nm, and the thickness of Y{sub 2}O{sub 3}:Eu hollow spherical shell is about 20-40nm. The photoluminescence spectra of SiO{sub 2}/Y{sub 2}O{sub 3}:Eu core-shell materials and Y{sub 2}O{sub 3}:Eu hollow spheres have better red luminescent properties, and the broadened emission bands came from the size effects of nanocrystals composed of Y{sub 2}O{sub 3}:Eu shell.

  13. The impact of P2Y12 promoter DNA methylation on the recurrence of ischemic events in Chinese patients with ischemic cerebrovascular disease

    PubMed Central

    Li, Xin-Gang; Ma, Ning; Wang, Bo; Li, Xiao-Qing; Mei, Sheng-Hui; Zhao, Kun; Wang, Yong-Jun; Li, Wei; Zhao, Zhi-Gang; Sun, Shu-Sen; Miao, Zhong-Rong

    2016-01-01

    The primary mechanism of clopidogrel resistance is still unclear. We aimed to investigate whether the methylation status of the P2Y12 promoter has effects on platelet function and clinical ischemic events. Patients with ischemic cerebrovascular disease were enrolled into our study. Venous blood samples were drawn for thrombelastograpy (TEG) and active metabolite assay. Patients were divided into a case- or control-group based on the occurrence of ischemic events during a one year follow-up. Two TEG parameters between the case and control groups were statistically significant [ADP inhibition rate (ADP%): P = 0.018; ADP-induced platelet-fibrin clot strength (MAADP): P = 0.030]. The concentrations of clopidogrel active metabolite had no significant difference (P = 0.281). Sixteen CpG dinucleotides on P2Y12 promoter were tested. Three CpG sites (CpG11 and CpG12 + 13) showed lower methylation status, which correlated with a strong association with increased risk of clinical events. Changes of MAADP and ADP% were also associated with methylation levels of CpG 11 and CpG 12 + 13. Hypomethylation of the P2Y12 promoter is associated with a higher platelet reactivity and increased risk of ischemic events in our patients. Methylation analysis of peripheral blood samples might be a novel molecular marker to help early identification of patients at high risk for clinical ischemic events. PMID:27686864

  14. Purinergic glio-endothelial coupling during neuronal activity: role of P2Y1 receptors and eNOS in functional hyperemia in the mouse somatosensory cortex.

    PubMed

    Toth, Peter; Tarantini, Stefano; Davila, Antonio; Valcarcel-Ares, M Noa; Tucsek, Zsuzsanna; Varamini, Behzad; Ballabh, Praveen; Sonntag, William E; Baur, Joseph A; Csiszar, Anna; Ungvari, Zoltan

    2015-12-01

    Impairment of moment-to-moment adjustment of cerebral blood flow (CBF) via neurovascular coupling is thought to play a critical role in the genesis of cognitive impairment associated with aging and pathological conditions associated with accelerated cerebromicrovascular aging (e.g., hypertension, obesity). Although previous studies demonstrate that endothelial dysfunction plays a critical role in neurovascular uncoupling in these conditions, the role of endothelial NO mediation in neurovascular coupling responses is not well understood. To establish the link between endothelial function and functional hyperemia, neurovascular coupling responses were studied in mutant mice overexpressing or deficient in endothelial NO synthase (eNOS), and the role of P2Y1 receptors in purinergic glioendothelial coupling was assessed. We found that genetic depletion of eNOS (eNOS(-/-)) and pharmacological inhibition of NO synthesis significantly decreased the CBF responses in the somatosensory cortex evoked by whisker stimulation and by administration of ATP. Overexpression of eNOS enhanced NO mediation of functional hyperemia. In control mice, the selective and potent P2Y1 receptor antagonist MRS2179 attenuated both whisker stimulation-induced and ATP-mediated CBF responses, whereas, in eNOS(-/-) mice, the inhibitory effects of MRS2179 were blunted. Collectively, our findings provide additional evidence for purinergic glio-endothelial coupling during neuronal activity, highlighting the role of ATP-mediated activation of eNOS via P2Y1 receptors in functional hyperemia. PMID:26453330

  15. The Effect of Microstructure on Mechanical Properties of Directionally Solidified Al2O3/ZrO2(Y2O3) Eutectic

    NASA Technical Reports Server (NTRS)

    Sayir, Ali; Farmer, Serene C.

    1999-01-01

    The eutectic architecture of a continuous reinforcing phase within a higher volume fraction phase or matrix can be described as a naturally occurring in-situ composite. Here we report the results of experiments aimed at identifying the sources of high temperature creep resistance and high levels of strength in a two phase Al2O3/ZrO2(Y2O3) system. The mechanical properties of two phase Al2O3/ZrO2(Y2O3) eutectic are superior to those of either constituent alone due to strong constraining effects provided by the coherent interfaces and microstructure. The AlO3/ZrO2(Y2O3) eutectic maintains a low energy interface resulting from directional solidification and can produce strong and stable reinforcing phase/matrix bonding. The phases comprising a eutectic are thermodynamically compatible at higher homologous temperatures than man-made composites and as such offer the potential for superior high temperature properties.

  16. 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.

  17. 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.

  18. Three-Dimensional Analysis of Retinal Layer Texture: Identification of Fluid-Filled Regions in SD-OCT of the Macula

    PubMed Central

    Lee, Kyungmoo; Dolejsi, Martin; Garvin, Mona K.; Abràmoff, Michael D.; Sonka, Milan

    2010-01-01

    Optical coherence tomography (OCT) is becoming one of the most important modalities for the noninvasive assessment of retinal eye diseases. As the number of acquired OCT volumes increases, automating the OCT image analysis is becoming increasingly relevant. In this paper, a method for automated characterization of the normal macular appearance in spectral domain OCT (SD-OCT) volumes is reported together with a general approach for local retinal abnormality detection. Ten intraretinal layers are first automatically segmented and the 3-D image dataset flattened to remove motion-based artifacts. From the flattened OCT data, 23 features are extracted in each layer locally to characterize texture and thickness properties across the macula. The normal ranges of layer-specific feature variations have been derived from 13 SD-OCT volumes depicting normal retinas. Abnormalities are then detected by classifying the local differences between the normal appearance and the retinal measures in question. This approach was applied to determine footprints of fluid-filled regions—SEADs (Symptomatic Exudate-Associated Derangements)—in 78 SD-OCT volumes from 23 repeatedly imaged patients with choroidal neovascularization (CNV), intra-, and sub-retinal fluid and pigment epithelial detachment. The automated SEAD footprint detection method was validated against an independent standard obtained using an interactive 3-D SEAD segmentation approach. An area under the receiver-operating characteristic curve of 0.961 ± 0.012 was obtained for the classification of vertical, cross-layer, macular columns. A study performed on 12 pairs of OCT volumes obtained from the same eye on the same day shows that the repeatability of the automated method is comparable to that of the human experts. This work demonstrates that useful 3-D textural information can be extracted from SD-OCT scans and—together with an anatomical atlas of normal retinas—can be used for clinically important applications

  19. The involvement of P2Y12 receptors, NADPH oxidase, and lipid rafts in the action of extracellular ATP on synaptic transmission at the frog neuromuscular junction.

    PubMed

    Giniatullin, A; Petrov, A; Giniatullin, R

    2015-01-29

    Adenosine 5'-triphosphate (ATP) is the main co-transmitter accompanying the release of acetylcholine from motor nerve terminals. Previously, we revealed the direct inhibitory action of extracellular ATP on transmitter release via redox-dependent mechanism. However, the receptor mechanism of ATP action and ATP-induced sources of reactive oxygen sources (ROS) remained not fully understood. In the current study, using microelectrode recordings of synaptic currents from the frog neuromuscular junction, we analyzed the receptor subtype involved in synaptic action of ATP, receptor coupling to NADPH oxidase and potential location of ATP receptors within the lipid rafts. Using subtype-specific antagonists, we found that the P2Y13 blocker 2-[(2-chloro-5-nitrophenyl)azo]-5-hydroxy-6-methyl-3-[(phosphonooxy)methyl]-4-pyridinecarboxaldehyde did not prevent the depressant action of ATP. In contrast, the P2Y12 antagonist 2-methylthioadenosine 5'-monophosphate abolished the inhibitory action of ATP, suggesting the key role of P2Y12 receptors in ATP action. As the action of ATP is redox-dependent, we also tested potential involvement of the NADPH oxidase, known as a common inducer of ROS. The depressant action of extracellular ATP was significantly reduced by diphenyleneiodonium chloride and 4-(2-aminoethyl)-benzenesulfonyl fluoride hydrochloride, two structurally different inhibitors of NADPH oxidase, indicating that this enzyme indeed mediates the action of ATP. Since the location and activity of various receptors are often associated with lipid rafts, we next tested whether ATP-driven inhibition depends on lipid rafts. We found that the disruption of lipid rafts with methyl-beta-cyclodextrin reduced and largely delayed the action of ATP. Taken together, these data revealed key steps in the purinergic control of synaptic transmission via P2Y12 receptors associated with lipid rafts, and identified NADPH oxidase as the main source of ATP-induced inhibitory ROS at the neuromuscular

  20. A model-based analysis of the clinical and economic impact of personalising P2Y12-receptor inhibition with platelet function testing in acute coronary syndrome patients.

    PubMed

    Straub, Niels; Beivers, Andreas; Lenk, Ekaterina; Aradi, Daniel; Sibbing, Dirk

    2014-02-01

    Although some observational studies reported that the measured level of P2Y12-inhibition is predictive for thrombotic events, the clinical and economic benefit of incorporating PFT to personalize P2Y12-receptor directed antiplatelet treatment is unknown. Here, we assessed the clinical impact and cost-effectiveness of selecting P2Y12-inhibitors based on platelet function testing (PFT) in acute coronary syndrome (ACS) patients undergoing PCI. A decision model was developed to analyse the health economic effects of different strategies. PFT-guided treatment was compared with the three options of general clopidogrel, prasugrel or ticagrelor treatment. In the PFT arm, low responders to clopidogrel received prasugrel, while normal responders carried on with clopidogrel. The associated endpoints in the model were cardiovascular death, stent thrombosis and major bleeding. With a simulated cohort of 10,000 patients treated for one year, there were 93 less events in the PFT arm compared to general clopidogrel. In prasugrel and ticagrelor arms, 110 and 86 events were prevented compared to clopidogrel treatment, respectively. The total expected costs (including event costs, drug costs and PFT costs) for generic clopidogrel therapy were US$ 1,059/patient. In the PFT arm, total costs were US$ 1,494, while in the prasugrel and ticagrelor branches they were US$ 3,102 and US$ 3,771, respectively. The incremental-cost-effectiveness-ratio (ICER) was US$ 46,770 for PFT-guided therapy, US$ 185,783 for prasugrel and US$ 315,360 for ticagrelor. In this model-based analysis, a PFT-guided therapy may have fewer adverse outcomes than general treatment with clopidogrel and may be more cost-effective than prasugrel or ticagrelor treatment in ACS patients undergoing PCI.

  1. G-protein-mediated activation of turkey erythrocyte phospholipase C by beta-adrenergic and P2y-purinergic receptors.

    PubMed Central

    Vaziri, C; Downes, C P

    1992-01-01

    Isoprenaline, previously known only to stimulate adenylate cyclase via the stimulatory G-protein, Gs, activates turkey erythrocyte ghost phospholipase C (PLC) in a dose-dependent manner when GTP or guanosine 5'-[gamma-thio]triphosphate (GTP[S]) is present. The effect is specific in that it is abolished by beta-adrenergic-receptor antagonists. Stimulation of adenosine receptors, which also couple to adenylate cyclase via Gs in turkey erythrocytes, does not activate PLC, indicating that the stimulation observed in the presence of isoprenaline is not due to Gs activation. Furthermore, the stimulation seen is independent of cyclic AMP production. Purified turkey erythrocyte PLC is activated in an adenosine 5'-[beta-thio]diphosphate (ADP[S]; a P2y-purinergic-receptor agonist)- or isoprenaline-regulated manner when reconstituted with turkey erythrocyte ghosts, demonstrating that a single species of PLC effector enzyme can be regulated by both the purinergic and the beta-adrenergic receptor populations present in turkey erythrocyte membranes. Pretreatment of intact turkey erythrocytes with the P2y agonist ADP[S] causes decreased PLC responsiveness of subsequent ghost preparations to ADP[S] stimulation, although responses to isoprenaline are unaffected (homologous desensitization). In contrast, pretreatment of intact erythrocytes with isoprenaline results in heterologous desensitization of both the P2y and the beta-adrenergic receptors. These effects occur at the level of receptor-G-protein coupling, since PLC stimulation by GTP[S] (which directly activates G-proteins) in the absence of agonists is unaffected. PMID:1352448

  2. Optical and scintillation properties of ce-doped (Gd2Y1)Ga2.7Al2.3O12 single crystal grown by Czochralski method

    NASA Astrophysics Data System (ADS)

    Wang, Chao; Wu, Yuntao; Ding, Dongzhou; Li, Huanying; Chen, Xiaofeng; Shi, Jian; Ren, Guohao

    2016-06-01

    Multicomponent garnets, due to their excellent light yield and energy resolution, become one of the most promising scintillators used for homeland security and nuclear non-proliferation applications. This work focuses on the optimization of Ce-doped (Gd,Y)3(Ga,Al)5O12 scintillators using a combination strategy of pre-screening and scale-up. Ce-doped GdxY1-xGayAl5-yO12 (x=1, 2 and y=2, 2.2, 2.5, 2.7, 3) polycrystalline powders were prepared by high-temperature solid state reaction method. The desired garnet phase in all the samples was confirmed using X-ray diffraction measurement. By comparing the radioluminescence intensity, the highest scintillation efficiency was achieved at a component of Gd2Y1Ga2.7Al2.3O12:Ce powders. A (Gd2Y1)Ga2.7Al2.3O12 doped with 1% Ce single crystal with dimensions of Ø35×40 mm was grown by Czochralski method using a <111> oriented seed. Luminescence and scintillation properties were measured. An optical transmittance of 84% was achieved in the concerned wavelength from 500 to 800 nm. Its 5d-4f emission of Ce3+ is at 530 nm. The light yield of a Ce1%: Gd2Y1Ga2.7Al2.3O12 single crystal slab at a size of 5×5×1 mm3 can reach about 65,000±3000 Ph/MeV along with two decay components of 94 and 615 ns under 137Cs source irradiation.

  3. P2Y2 receptor activation inhibits the expression of the sodium-chloride cotransporter NCC in distal convoluted tubule cells.

    PubMed

    Gailly, P; Szutkowska, M; Olinger, E; Debaix, H; Seghers, F; Janas, S; Vallon, V; Devuyst, O

    2014-11-01

    Luminal nucleotide stimulation is known to reduce Na(+) transport in the distal nephron. Previous studies suggest that this mechanism may involve the thiazide-sensitive Na(+)-Cl(-) cotransporter (NCC), which plays an essential role in NaCl reabsorption in the cells lining the distal convoluted tubule (DCT). Here we show that stimulation of mouse DCT (mDCT) cells with ATP or UTP promoted Ca(2+) transients and decreased the expression of NCC at both mRNA and protein levels. Specific siRNA-mediated silencing of P2Y2 receptors almost completely abolished ATP/UTP-induced Ca(2+) transients and significantly reduced ATP/UTP-induced decrease of NCC expression. To test whether local variations in the intracellular Ca(2+) concentration ([Ca(2+)]i) may control NCC transcription, we overexpressed the Ca(2+)-binding protein parvalbumin selectively in the cytosol or in the nucleus of mDCT cells. The decrease in NCC mRNA upon nucleotide stimulation was abolished in cells overexpressing cytosolic PV but not in cells overexpressing either a nuclear-targeted PV or a mutated PV unable to bind Ca(2+). Using a firefly luciferase reporter gene strategy, we observed that the activity of NCC promoter region from -1 to -2,200 bp was not regulated by changes in [Ca(2+)]i. In contrast, high cytosolic calcium level induced instability of NCC mRNA. We conclude that in mDCT cells: (1) P2Y2 receptor is essential for the intracellular Ca(2+) signaling induced by ATP/UTP stimulation; (2) P2Y2-mediated increase of cytoplasmic Ca(2+) concentration down-regulates the expression of NCC; (3) the decrease of NCC expression occurs, at least in part, via destabilization of its mRNA.

  4. Crystal structure and luminescence properties of Bi3+activated Ca2Y8(SiO4)6O2 phosphors under near UV excitation

    NASA Astrophysics Data System (ADS)

    Sun, Zhihua; Wang, Minqiang; Yang, Zhi; Liu, Kaiping; Zhu, Feiyan

    2016-07-01

    Oxyapatite Ca2Y8-x(SiO4)6O2:xBi3+phosphor has been prepared via high temperature solid-state reaction. Its crystal structure and PL properties were investigated by X-ray diffraction, photoluminescence excitation and emission spectra. The results indicated that the Ca2Y8(SiO4)6O2 crystallizes as a hexagonal structure with a space group of P63/m and lattice constants of a=b=9.3507 Å, c=6.7899 Å, α=β=90.00°, γ=120.00°, V=514.14 Å3; The phosphor has two prominent emission bands: when excited under 320-360 nm, the phosphors emit a broad band centered at 495 nm due to the 3P1-1S0 transition of Bi3+ in 4f (C3) sites; when excited under 380 nm, the phosphors emit a broad band centered at 411 nm due to the 3P1-1S0 transition of Bi3+ in 6h (Cs) sites. The emission color varies from the greenish blue to blue as the excitation wavelength increases from 335 to 380 nm. The optimal intensity of emission band was observed when x=0.015 in the Ca2Y8-x(SiO4)6O2:xBi3+ series. The average critical distance Rc among Bi3+ ions is determined to be 20.15 Å.

  5. P2 purinoceptor-mediated control of rat cerebral (pial) microvasculature; contribution of P2X and P2Y receptors

    PubMed Central

    Lewis, C J; Ennion, S J; Evans, R J

    2000-01-01

    Purine and pyrimidine nucleotides evoke changes in the vascular tone of medium to large cerebral vessels through the activation of P2 purinoceptors. We have applied P2 receptor drugs to rat pial arterioles and measured changes in arteriole diameter (o.d. 40–84 μm at rest), and recorded currents from arteriolar smooth muscle cells using patch-clamp techniques. Transient vasoconstrictions and rapidly inactivating currents were evoked by α,β-methylene ATP (0.1–30 μm) and were sensitive to the P2 receptor antagonists suramin and iso-PPADS. UTP and UDP (0.1–1000 μm) evoked sustained suramin-sensitive vasoconstrictions. ATP (0.1–1000 μm) and 2-methylthioATP (2MeSATP, 300 μm) evoked transient vasoconstrictions followed by sustained vasodilatations. ADP application resulted in only vasodilatation (EC50 ∼4 μm). Vasodilator responses to ATP, 2MeSATP or ADP were unaffected by suramin (100 μm). RT-PCR analysis indicated that P2X1–7 and P2Y1,2,6 RNA can be amplified from the pial sheet. Our results provide direct evidence for the presence of functional P2X receptors with a phenotype resembling the P2X1 receptor subtype on cerebral resistance arterioles. The pharmacological properties of the pyrimidine-evoked responses suggest that a combination of P2Y2- and P2Y6-like receptors are responsible for the sustained vasoconstrictions. It is therefore likely that the nucleotides and their associated receptors are involved in a complicated regulatory system to control cerebral blood pressure. PMID:10970432

  6. Homodimeric anoctamin-1, but not homodimeric anoctamin-6, is activated by calcium increases mediated by the P2Y1 and P2X7 receptors.

    PubMed

    Stolz, Michaela; Klapperstück, Manuela; Kendzierski, Thomas; Detro-Dassen, Silvia; Panning, Anna; Schmalzing, Günther; Markwardt, Fritz

    2015-10-01

    The P2X7 receptor (P2X7R) is a ligand-gated ion channel that conducts Na(+), K(+), and Ca(2+) when activated by extracellular ATP. In various cell types, such as secretory epithelia, the P2X7R is co-expressed with Ca(2+)-dependent Cl(-) channels of the TMEM16/anoctamin family. Here, we studied whether the P2X7R and TMEM16A/anoctamin-1 (Ano1) or TMEM16F/anoctamin-6 (Ano6) interact functionally and physically, using oocytes of Xenopus laevis and Ambystoma mexicanum (Axolotl) for heterologous expression. As a control, we co-expressed anoctamin-1 with the P2Y1 receptor (P2Y1R), which induces the release of Ca(2+) from intracellular stores via activating phospholipase C through coupling to Gαq. We found that co-expression of anoctamin-1 with the P2Y1R resulted in a small transient increase in Cl(-) conductance in response to ATP. Co-expression of anoctamin-1 with the P2X7R resulted in a large sustained increase in Cl(-) conductance via Ca(2+) influx through the ATP-opened P2X7R in Xenopus and in Axolotl oocytes, which lack endogenous Ca(2+)-dependent Cl(-) channels. P2Y1R- or P2X7R-mediated stimulation of Ano1 was primarily functional, as demonstrated by the absence of a physically stable interaction between Ano1 and the P2X7R. In the pancreatic cell line AsPC-1, we found the same functional Ca(2+)-dependent interaction of P2X7R and Ano1. The P2X7R-mediated sustained activation of Ano1 may be physiologically relevant to the time course of stimulus-secretion coupling in secretory epithelia. No such increase in Cl(-) conductance could be elicited by activating the P2X7 receptor in either Xenopus oocytes or Axolotl oocytes co-expressing Ano6. The lack of function of Ano6 can, at least in part, be explained by its poor cell-surface expression, resulting from a relatively inefficient exit of the homodimeric Ano6 from the endoplasmic reticulum.

  7. Influence of doping on the physical properties of Ca10-xRExPt3As8(Fe2-yPtyAs2)5

    NASA Astrophysics Data System (ADS)

    Pan, Jiayun; Karki, Amar; Jin, Rongying

    2015-03-01

    Ca10-xRExPt3As8(Fe2-yPtyAs2)5 is a new FeAs-based superconductor. We report the change of its superconducting transition temperature Tc and physical properties upon chemical doping in either Ca (using La or Gd) or Fe (using Pt) site. While partial replacement of Fe by Pt results in Tc up to 21 K , we find that the substitution of Ca by La is most effective pushing Tc to 30 K. The doping in both sites reduces the in-plane resistivity and anisotropy. The doping dependance of electrical transport properties will be presented and discussed.

  8. Homodimeric anoctamin-1, but not homodimeric anoctamin-6, is activated by calcium increases mediated by the P2Y1 and P2X7 receptors.

    PubMed

    Stolz, Michaela; Klapperstück, Manuela; Kendzierski, Thomas; Detro-Dassen, Silvia; Panning, Anna; Schmalzing, Günther; Markwardt, Fritz

    2015-10-01

    The P2X7 receptor (P2X7R) is a ligand-gated ion channel that conducts Na(+), K(+), and Ca(2+) when activated by extracellular ATP. In various cell types, such as secretory epithelia, the P2X7R is co-expressed with Ca(2+)-dependent Cl(-) channels of the TMEM16/anoctamin family. Here, we studied whether the P2X7R and TMEM16A/anoctamin-1 (Ano1) or TMEM16F/anoctamin-6 (Ano6) interact functionally and physically, using oocytes of Xenopus laevis and Ambystoma mexicanum (Axolotl) for heterologous expression. As a control, we co-expressed anoctamin-1 with the P2Y1 receptor (P2Y1R), which induces the release of Ca(2+) from intracellular stores via activating phospholipase C through coupling to Gαq. We found that co-expression of anoctamin-1 with the P2Y1R resulted in a small transient increase in Cl(-) conductance in response to ATP. Co-expression of anoctamin-1 with the P2X7R resulted in a large sustained increase in Cl(-) conductance via Ca(2+) influx through the ATP-opened P2X7R in Xenopus and in Axolotl oocytes, which lack endogenous Ca(2+)-dependent Cl(-) channels. P2Y1R- or P2X7R-mediated stimulation of Ano1 was primarily functional, as demonstrated by the absence of a physically stable interaction between Ano1 and the P2X7R. In the pancreatic cell line AsPC-1, we found the same functional Ca(2+)-dependent interaction of P2X7R and Ano1. The P2X7R-mediated sustained activation of Ano1 may be physiologically relevant to the time course of stimulus-secretion coupling in secretory epithelia. No such increase in Cl(-) conductance could be elicited by activating the P2X7 receptor in either Xenopus oocytes or Axolotl oocytes co-expressing Ano6. The lack of function of Ano6 can, at least in part, be explained by its poor cell-surface expression, resulting from a relatively inefficient exit of the homodimeric Ano6 from the endoplasmic reticulum. PMID:25592660

  9. A Dilatometric Study of Sintering of Composite Ceramics Manufactured from Ultrafine Zro2(Y)-Al2O3 Powders Under Different Thermal-Temporal Firing Conditions

    NASA Astrophysics Data System (ADS)

    Surzhikov, A. P.; Frangulyan, T. S.; Ghyngazov, S. A.; Vasiliev, I. P.

    2014-07-01

    Using dilatometry, kinetic principles of sintering of composite ZrO2(Y)-Al2O3 ceramic material made from ultrafine powders synthesized at the Siberian Chemical Integrated Works are investigated. It is shown that under heating conditions, sintering of the composite ceramics under study occurs within a few stages that are closely related to the structural-phase transformations taking place in the composite powder mixture. At the firing temperatures Т > 1500 С and during long isothermal times, negative phenomena develop in the ceramic material, which give rise to its undesired dilatation and cracking in the course of cooling.

  10. Formation of superconducting Bi sub 2-y Pb sub y Sr sub 2 Ca sub 2 Cu sub 3 O sub x from coprecipitated oxalates

    SciTech Connect

    Bernhard, K.; Gritzner, G.; Wang, Xianzhong; Baeuerle, D. )

    1990-06-01

    The conditions for the coprecipitation of Bi{sup 3+}, Pb{sup 2+}, Ca{sup 2+} as oxalates are reported. These oxalates were used as precursors for the formation of Bi{sub 2-y}Pb{sub y}Sr{sub 2}Ca{sub 2}Cu{sub 3}O{sub x} superconducting ceramics. The behavior of the oxalates upon heat treatment was studied by thermogravimetry. Both the oxalates and the superconducting oxides were analyzed and characterized by atomic absorption spectroscopy and by X-ray diffraction.

  11. Synthesis and structural analysis of Bi{sub 2-y}Sr{sub y}Ir{sub 2}O{sub 7}, a new pyrochlore solid solution

    SciTech Connect

    Cosio-Castaneda, Carlos; Mora, Pablo de la; Tavizon, Gustavo

    2011-05-15

    This paper presents a study of the synthesis and structural properties of the new pyrochlore-type Bi{sub 2-y}Sr{sub y}Ir{sub 2}O{sub 7} series. Ten compositions with 0.0{<=}y{<=}0.9 were prepared by solid-state reaction with thermal treatments at 873, 1073 and 1323 K under atmospheric pressure conditions. Structural refinements from X-ray powder diffraction data by the Rietveld method show that all compounds of the Bi{sub 2-y}Sr{sub y}Ir{sub 2}O{sub 7} solid solution crystallize in a {alpha}-pyrochlore structure. The main structural difference when bismuth is substituted by strontium concerns the x position of the O1 (x, (1/8), (1/8)). This substitution significantly increases the Bi/Sr-O1 distance and diminishes the Ir-O1 distance; this implies that the Ir-O1-Ir bond angle increases. With the Sr substitution, the IrO{sub 6} local configuration goes from a flattened trigonal antiprism, y<0.5, to an elongated one, y>0.5, passing through an octahedral array, y{approx}0.5. The electrical consequences of these structural changes observed in this system are qualitatively explained with electronic structure calculations, this behavior agrees very well with those observed in other pyrochlore systems A{sub 2}M{sub 2}O{sub 7} (A=rare earth cations or Tl{sup +}, Pb{sup 2+}, or Bi{sup 3+}, and M=Ru or Ir). -- Graphical abstract: Electrical behavior of the Bi{sub 2-y}Sr{sub y}Ir{sub 2}O{sub 7} solid solution. Display Omitted Highlights: {yields} Bi{sub 2-y}Sr{sub y}Ir{sub 2}O{sub 7} crystallizes in the {alpha}-pyrochlore structure. {yields} Local geometry of Ir goes from a flattened trigonal antiprism to an elongated one. {yields} Electrical resistivity increases with the Sr content in the solid solution. {yields} Electronic structure analysis relates resistivity with Sr disorder and bond strength.

  12. Effects of Soluble Phosphate on Phosphate-Solubilizing Characteristics and Expression of gcd Gene in Pseudomonas frederiksbergensis JW-SD2.

    PubMed

    Zeng, Qingwei; Wu, Xiaoqin; Wen, Xinyi

    2016-02-01

    Phosphate-solubilizing bacteria have the ability of solubilizing mineral phosphate in soil and promoting growth of plants, but the activity of phosphate solubilization is influenced by exogenous soluble phosphate. In the present study, the effects of soluble phosphate on the activity of phosphate solubilization, acidification of media, growth, and organic acid secretion of phosphate-solubilizing bacterium Pseudomonas frederiksbergensis JW-SD2 were investigated under six levels of soluble phosphate conditions. The activity of phosphate solubilization decreased with the increase of soluble phosphate concentration, accompanying with the increase of media pH. However, the growth was promoted by adding soluble phosphate. Production of gluconic, tartaric, and oxalic acids by the strain was reduced with the increase of concentration of soluble phosphate, while acetic and pyruvic acids showed a remarkable increase. Gluconic acid predominantly produced by the strain at low levels of soluble phosphate showed that this acid was the most efficient organic acid in phosphate solubilization. Pyrroloquinoline quinone-glucose dehydrogenase gene gcd (pg5SD2) was cloned from the strain, and the expressions of pg5SD2 gene were repressed gradually with the increase of concentration of soluble phosphate. The soluble phosphate regulating the transcription of the gcd gene is speculated to underlie the regulation of the secretion of gluconic acid and subsequently the regulation of the activity of phosphate solubilization. Future research needs to consider a molecular engineering strategy to reduce the sensitivity of PSB strain to soluble phosphate via modification of the regulatory mechanism of gcd gene, which could improve the scope of PSB strains' application.

  13. Reliability of manual measurements of corneal thickness obtained from healthy canine eyes using spectral-domain optical coherence tomography (SD-OCT).

    PubMed

    Alario, Anthony F; Pirie, Christopher G

    2014-07-01

    The purpose of this study was to manually measure corneal thickness in canine eyes using a spectral-domain optical coherence tomography (SD-OCT) device and to assess intra- and inter-observer reliability of this technique. Twenty healthy dogs with a mean age of 4.7 y were examined. A 6-mm corneal pachymetry protocol was carried out by 1 operator using 1 SD-OCT device in both eyes of each animal. Measurements were obtained manually and in duplicate by 2 independent investigators (> 24 h apart), using the built-in caliper function. Measurements included epithelial thickness (ET), non-epithelial thickness (NET), and central corneal thickness (CCT). The overall mean ET, NET, and CCT for all eyes examined were 72.3 ± 4.6 μm, 538.9 ± 42.5 μm, and 611.2 ± 40.3 μm, respectively. There was no significant difference in ET, NET, or CCT based on the eye examined [oculus dexter (OD) versus oculus sinister (OS)], age, or gender of the animal. There was no significant difference in replicate measurements of ET, NET, or CCT done by the same operator, although a small but significant difference was noted between operators for ET measurements only. The mean difference in ET between operators was 0.6 μm (P = 0.03). The coefficient of variation ranged from 0.5% to 9.27% and intraclass correlation coefficient ranged from 0.35 to 0.97. Based on these results, manual measurements of corneal thickness in canine eyes using a portable SD-OCT device provided ET, NET, and CCT measurements with clinically acceptable intra- and inter-observer reliability.

  14. SD 1313-0019: Another Second-generation Star with [Fe/H] = -5.0, Observed with the Magellan Telescope

    NASA Astrophysics Data System (ADS)

    Frebel, Anna; Chiti, Anirudh; Ji, Alexander P.; Jacobson, Heather R.; Placco, Vinicius M.

    2015-09-01

    We present a Magellan/MIKE high-resolution (R ˜ 35,000) spectrum of the ancient star SD 1313-0019, which has an iron abundance of [Fe/H]=-5.0, paired with a carbon enhancement of [C/Fe]˜ 3.0. The star was initially identified by Allende Prieto et al. in the BOSS survey. Its medium-resolution spectrum suggested a higher metallicity of [Fe/H]=-4.3 due to the Ca II K line blending with a CH feature, which is a common issue related to the search for the most iron-poor stars. This star joins several other similar stars with [Fe/H]≲ -5.0 that all display a combination of low-iron and high-carbon abundances. Other elemental abundances of SD 1313-0019 follow that of more metal-rich halo stars. Fitting the abundance pattern with yields of Population III supernovae suggests that SD 1313-0019 had only one massive progenitor star with 20-30 M⊙ that must have undergone a mixing and fallback episode. Overall, there are now five stars known with [Fe/H]≲ -5.0 (1D local thermodynamic equilibrium abundances). This ever-increasing population of carbon-rich, iron-deficient stars can potentially constrain nucleosynthesis in Population III stars and their supernova explosions, the formation mechanisms of the first low-mass stars, and the nature of the first galaxies. This paper includes data gathered with the 6.5 m Magellan Telescopes located at Las Campanas Observatory, Chile.

  15. Development of quercetin-phospholipid complex to improve the bioavailability and protection effects against carbon tetrachloride-induced hepatotoxicity in SD rats.

    PubMed

    Zhang, Kexia; Zhang, Meiyu; Liu, Ziying; Zhang, Yuanyuan; Gu, Liqiang; Hu, Gaosheng; Chen, Xiaohui; Jia, Jingming

    2016-09-01

    Quercetin (QT) is a natural flavonoid with various biological activities and pharmacological actions. However, the bioavailability of QT is relatively low due to its low solubility which severely limits its use. In this study, we intended to improve the bioavailability of QT by preparing quercetin-phospholipid complex (QT-PC) and investigate the protective effect of QT-PC against carbon tetrachloride (CCl4) induced acute liver damage in Sprague-Dawley (SD) rats. The physicochemical properties of QT-PC were characterized in terms of infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (XRPD) and water/n-octanol solubility. FTIR, DSC and XRPD data confirmed the formation of QT-PC. The water solubility of QT was improved significantly in the prepared complex, indicating its increased hydrophilicity. Oral bioavailability of QT and QT-PC was evaluated in SD rats, and the plasma QT was estimated by HPLC-MS. QT-PC exhibited higher Cmax (1.58±0.11 vs. 0.67±0.08μg/mL), increased AUC0-∞ (8.60±1.25 vs. 2.41±0.51mg/Lh) and t1/2z (7.76±1.09 vs. 4.81±0.87h) when compared to free QT. The greater absorption of QT-PC group suggested the improved bioavailability. Moreover, biochemical changes and histopathological observations revealed that QT-PC provided better protection to rat liver than free QT at the same dose. Thus, phospholipid complexation might be one of the suitable approaches to improve the oral bioavailability of QT and obtain better protective effects against CCl4 induced acute liver damage in SD rats than free QT at the same dose level. PMID:27431774

  16. Transient activation and delayed inhibition of Na+,K+,Cl- cotransport in ATP-treated C11-MDCK cells involve distinct P2Y receptor subtypes and signaling mechanisms.

    PubMed

    Akimova, Olga A; Grygorczyk, Alexandra; Bundey, Richard A; Bourcier, Nathalie; Gekle, Michael; Insel, Paul A; Orlov, Sergei N

    2006-10-20

    In C11-MDCK cells, which resemble intercalated cells from collecting ducts of the canine kidney, P2Y agonists promote transient activation of the Na+,K+,Cl- cotransporter (NKCC), followed by its sustained inhibition. We designed this study to identify P2Y receptor subtypes involved in dual regulation of this carrier. Real time polymerase chain reaction analysis demonstrated that C11-MDCK cells express abundant P2Y1 and P2Y2 mRNA compared with that of other P2Y receptor subtypes. The rank order of potency of agents (ATP approximately UTP > 2-(methylthio)-ATP (2MeSATP); adenosine 5'-[beta-thio]diphosphate (ADPbetaS) inactive) indicated that P2Y2 rather than P2Y1 receptors mediate a 3-4-fold activation of NKCC within the first 5-10 min of nucleotide addition. NKCC activation in ATP-treated cells was abolished by the intracellular calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, calmodulin (CaM) antagonists trifluoroperazine and W-7, and KN-62, an inhibitor of Ca2+/CaM-dependent protein kinase II. By contrast with the transient activation, 30-min incubation with nucleotides produced up to 4-5-fold inhibition of NKCC, and this inhibition exhibited a rank order of potency (2MeSATP > ADPbetaS > ATP > UTP) typical of P2Y1 receptors. Unlike the early response, delayed inhibition of NKCC occurred in 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-loaded cells and was completely abolished by the P2Y1 antagonists MRS2179 and MRS2500. Transient activation and delayed inhibition of NKCC in C11 cell monolayers were observed after the addition of ATP to mucosal and serosal solutions, respectively. NKCC inhibition triggered by basolateral application of ADPbetaS was abolished by MRS2500. Our results thus show that transient activation and delayed inhibition of NKCC in ATP-treated C11-MDCK cells is mediated by Ca2+/CaM-dependent protein kinase II- and Ca2+-independent signaling triggered by apical P2Y2 and basolateral P2Y1 receptors, respectively

  17. Synthesis and spectroscopic properties of zeolite-entrapped bis-heteroleptic ruthenium(II) polypyridine complexes. [Ru sup 2+ (bpy) sub 2 (bpz) sup 2+ -Y and Ru sup 2+ (bpy) sub 2 (dmb) sup 2+ -Y where bpy is bipyridine, bpz is bipyrazine, dmp is 4,4'-dimethyl-2,2'-bipyridine, and Y is zeolite

    SciTech Connect

    Maruszewski, K.; Kincaid, J.R. ); Strommen, D.P.; Handrich, K. )

    1991-11-27

    A convenient method for the preparation of polypyridine complexes of Ru(II) within the supercages of zeolite Y is reported. The bis-heteroleptic trisligated species Ru{sup 2+}(bpy){sub 2}(bpz){sup 2+}-Y and Ru{sup 2+}(bpy){sub 2}(dmb){sup 2+}-Y have been obtained and characterized by electronic absorption and resonance Raman spectroscopies. Two methods of zeolite matrix destruction have been used to extract the zeolite-entrapped complexes. Depending on experimental conditions, a blue byproduct can be formed in the zeolite supercages. Preliminary evidence suggests that this compound is properly formulated as Ru{sup 3+}(bpy){sub 2}(X)0-(where X is unspecified) bound to the supercage interior wall via an oxygen atom donated by the zeolite.

  18. An EPR investigation of the dynamic Jahn-Teller effect in SrCl2:y(2 plus) and SrCl2:Sc(2 plus)

    NASA Technical Reports Server (NTRS)

    Herrington, J. R.; Estle, T. L.; Boatner, L. A.

    1972-01-01

    EPR spectra have been observed for SrCl2:Y(2+) and SrCl2:Sc(2+) at liquid helium temperatures. At 1.2 K the spectra were dominated by anisotropic hyperfine patterns whose lineshapes and angular dependences were explained using second order solutions of the effective Hamiltonian for an isolated 2Eg state split by large random internal strains. Pronounced asymmetries in some of the strin produced lineshapes for Srcl2:Sc(2+) are shown to result from second order terms in the solution of the effective Hamiltonian. Coexisting with the anisotropic hyperfine patterns are weak nearly isotropic hyperfine patterns with typical lineshapes. Variations in the apparent intensity of lines in these weak hyperfine patterns as functions of the applied magnetic field direction and temperature imply that these lines result from averaging by vibronic relaxation of a portion of the anisotropic pattern. The effective Hamiltonian parameters for SrCl2:La(2+), SrCl2:y(2+), and SrCl2:SC(2+) are analyzed in terms of crystal field theory modified to include a dynamic Jahn-Teller effect.

  19. High Energy Magnetic Excitations from the Edge-sharing CuO2 Chains in Ca2Y2Cu5O10

    NASA Astrophysics Data System (ADS)

    Matsuda, Masaaki; Kakurai, Kazuhisa; Yethiraj, Mohana; Oka, Kunihiko

    2005-05-01

    Ca2Y2Cu5O10 is a quasi-one-dimensional magnet, which consists of the ferromagnetic edge-sharing CuO2 chains. It was previously reported from neutron inelastic scattering experiments in Ca2Y2Cu5O10 up to ˜14 meV that in the magnetically ordered state there is an anomalous broadening of spin-wave excitations along the chain, which is caused mainly by the antiferromagnetic interchain interactions [M. Matsuda et al.: Phys. Rev. B 63 (2001) 180403(R)]. In this study we extended an energy range of the measurement up to ˜25 meV. The experimental result suggests that there exist two excitation modes, which is consistent with a theoretical result qualitatively. One mode corresponds to the relatively sharp spin-wave excitations, which broaden with increasing qchain and disappear around qchain˜ 0.2 r.l.u. and ω˜ 10 meV. Another one corresponds to the very broad excitations apparent at qchain˜ 0.2--0.3 r.l.u. and ω˜ 12--25 meV.

  20. Direct observation of nanoscale interface phase in the superconducting chalcogenide KxFe2 -ySe2 with intrinsic phase separation

    NASA Astrophysics Data System (ADS)

    Ricci, A.; Poccia, N.; Joseph, B.; Innocenti, D.; Campi, G.; Zozulya, A.; Westermeier, F.; Schavkan, A.; Coneri, F.; Bianconi, A.; Takeya, H.; Mizuguchi, Y.; Takano, Y.; Mizokawa, T.; Sprung, M.; Saini, N. L.

    2015-01-01

    We have used scanning micro x-ray diffraction to characterize different phases in superconducting KxFe2 -ySe2 as a function of temperature, unveiling the thermal evolution across the superconducting transition temperature (Tc˜32 K), phase separation temperature (Tp s˜520 K), and iron-vacancy order temperature (Tv o˜580 K). In addition to the iron-vacancy ordered tetragonal magnetic phase and orthorhombic metallic minority filamentary phase, we have found clear evidence of the interface phase with tetragonal symmetry. The metallic phase is surrounded by this interface phase below ˜300 K, and is embedded in the insulating texture. The spatial distribution of coexisting phases as a function of temperature provides clear evidence of the formation of protected metallic percolative paths in the majority texture with large magnetic moment, required for the electronic coherence for the superconductivity. Furthermore, a clear reorganization of iron-vacancy order around the Tp s and Tc is found with the interface phase being mostly associated with a different iron-vacancy configuration, that may be important for protecting the percolative superconductivity in KxFe2 -ySe2 .

  1. Polyamidoamine (PAMAM) Dendrimer Conjugates of Clickable Agonists of the A3 Adenosine Receptor and Coactivation of the P2Y14 Receptor by a Tethered Nucleotide

    SciTech Connect

    Tosh, Dilip, K.; Yoo, Lena S.; Chinn, Moshe; Hong, Kunlun; Kilbey, II, S Michael; Barrett, Matthew O.; Fricks, Ingrid P.; Harden, T. Kendall; Jacobson, Kenneth A.

    2010-01-01

    We previously synthesized a series of potent and selective A{sub 3} adenosine receptor (AR) agonists (North-methanocarba nucleoside 5{prime}-uronamides) containing dialkyne groups on extended adenine C2 substituents. We coupled the distal alkyne of a 2-octadiynyl nucleoside by Cu(I)-catalyzed 'click' chemistry to azide-derivatized G4 (fourth-generation) PAMAM dendrimers to form triazoles. A{sub 3}AR activation was preserved in these multivalent conjugates, which bound with apparent Ki of 0.1-0.3 nM. They were substituted with nucleoside moieties, solely or in combination with water-solubilizing carboxylic acid groups derived from hexynoic acid. A comparison with various amide-linked dendrimers showed that triazole-linked conjugates displayed selectivity and enhanced A{sub 3}AR affinity. We prepared a PAMAM dendrimer containing equiproportioned peripheral azido and amino groups for conjugation of multiple ligands. A bifunctional conjugate activated both A{sub 3} and P2Y{sub 14} receptors (via amide-linked uridine-5{prime}-diphosphoglucuronic acid), with selectivity in comparison to other ARs and P2Y receptors. This is the first example of targeting two different GPCRs with the same dendrimer conjugate, which is intended for activation of heteromeric GPCR aggregates. Synergistic effects of activating multiple GPCRs with a single dendrimer conjugate might be useful in disease treatment.

  2. Synthesis and structural analysis of Bi 2- ySr yIr 2O 7, a new pyrochlore solid solution

    NASA Astrophysics Data System (ADS)

    Cosio-Castaneda, Carlos; de la Mora, Pablo; Tavizon, Gustavo

    2011-05-01

    This paper presents a study of the synthesis and structural properties of the new pyrochlore-type Bi 2- ySr yIr 2O 7 series. Ten compositions with 0.0≤ y≤0.9 were prepared by solid-state reaction with thermal treatments at 873, 1073 and 1323 K under atmospheric pressure conditions. Structural refinements from X-ray powder diffraction data by the Rietveld method show that all compounds of the Bi 2- ySr yIr 2O 7 solid solution crystallize in a α-pyrochlore structure. The main structural difference when bismuth is substituted by strontium concerns the x position of the O1 ( x, ⅛, ⅛). This substitution significantly increases the Bi/Sr-O1 distance and diminishes the Ir-O1 distance; this implies that the Ir-O1-Ir bond angle increases. With the Sr substitution, the IrO 6 local configuration goes from a flattened trigonal antiprism, y<0.5, to an elongated one, y>0.5, passing through an octahedral array, y˜0.5. The electrical consequences of these structural changes observed in this system are qualitatively explained with electronic structure calculations, this behavior agrees very well with those observed in other pyrochlore systems A2M2O 7 ( A=rare earth cations or Tl +, Pb 2+, or Bi 3+, and M=Ru or Ir).

  3. Synthesis and Characterization of SiO2@Y2MoO6:Eu3+ Core-Shell Structured Spherical Phosphors by Sol-Gel Process.

    PubMed

    Li, G Z; Liu, F H; Chu, Z S; Wu, D M; Yang, L B; Li, J L; Wang, M N; Wang, Z L

    2016-04-01

    SiO2@Y2MoO6:Eu3+ core-shell phosphors were prepared by the sol-gel process. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectra (EDS), transmission electron microscopy (TEM), photoluminescence (PL) spectra as well as kinetic decays were used to characterize the resulting SiO2@Y2MoO6:Eu3+ core-shell phosphors. The XRD results demonstrated that the Y2MoO6:Eu3+ layers on the SiO2 spheres crystallized after being annealed at 700 °C and the crystallinity increased with raising the annealing temperature. The obtained core-shell phosphors have spherical shape with narrow size distribution (average size ca. 640 nm), non-agglomeration, and smooth surface. The thickness of the Y2MoO6:Eu3+ shells on the SiO2 cores could be easily tailored by varying the number of deposition cycles (70 nm for four deposition cycles). The Eul+ shows a strong PL emission (dominated by 5D0-7F2 red emission at 614 nm) under the excitation of 347 nm UV light. The PL intensity of Eu3+ increases with increasing the annealing temperature and the number of coating cycles. PMID:27451737

  4. Structure-activity relationships of lysophosphatidylserine analogs as agonists of G-protein-coupled receptors GPR34, P2Y10, and GPR174.

    PubMed

    Ikubo, Masaya; Inoue, Asuka; Nakamura, Sho; Jung, Sejin; Sayama, Misa; Otani, Yuko; Uwamizu, Akiharu; Suzuki, Keisuke; Kishi, Takayuki; Shuto, Akira; Ishiguro, Jun; Okudaira, Michiyo; Kano, Kuniyuki; Makide, Kumiko; Aoki, Junken; Ohwada, Tomohiko

    2015-05-28

    Lysophosphatidylserine (LysoPS) is an endogenous lipid mediator generated by hydrolysis of membrane phospholipid phosphatidylserine. Recent ligand screening of orphan G-protein-coupled receptors (GPCRs) identified two LysoPS-specific human GPCRs, namely, P2Y10 (LPS2) and GPR174 (LPS3), which, together with previously reported GPR34 (LPS1), comprise a LysoPS receptor family. Herein, we examined the structure-activity relationships of a series of synthetic LysoPS analogues toward these recently deorphanized LysoPS receptors, based on the idea that LysoPS can be regarded as consisting of distinct modules (fatty acid, glycerol, and l-serine) connected by phosphodiester and ester linkages. Starting from the endogenous ligand (1-oleoyl-LysoPS, 1), we optimized the structure of each module and the ester linkage. Accordingly, we identified some structural requirements of each module for potency and for receptor subtype selectivity. Further assembly of individually structure-optimized modules yielded a series of potent and LysoPS receptor subtype-selective agonists, particularly for P2Y10 and GPR174. PMID:25970039

  5. Effect of fuel to air ratio on Mach 0.3 burner rig hot corrosion of ZrO2-Y2O3 thermal barrier coatings

    NASA Technical Reports Server (NTRS)

    Hodge, P. E.

    1982-01-01

    A Mach 0.3 burner rig test program was conducted to determine how the fuel to air mass ratio affects the durability of ZrO2-Y2O3/Ni-16Cr-6Al-0.31Y thermal barrier coating systems in combustion products containing 5 ppm Na and 2 ppm V. As the fuel to air mass ratio was increased from 0.039 to 0.049, the durability of ZrO2-6Y2O3, ZrO2-8Y2O3 and ZrO2-12Y2O3 coatings decreased. ZrO2-8Y2O3 coatings were approximately 2X and 1.3X more durable than ZrO2-12Y2O3 and ZrO2-6Y2O3 coatings respectively at the fuel to air mass ratio of 0.039. The number of one hour cycles endured by ZrO2-8Y2O3 coatings varied from averages of 53 to 200 for the fuel to air mass ratios of 0.049 and 0.039, respectively. At the fuel to air mass ratio of 0.049, all ZrO2-Y2O3 coated specimens failed in 40 to 60 one hour cycles

  6. Vibrational relaxation dynamics of SD molecules in As{sub 2}S{sub 3}: Observation of an anomalous isotope effect

    SciTech Connect

    Engholm, J.R.; Happek, U.; Rella, C.W.

    1995-12-31

    It is generally assumed that the vibrational relaxation of molecular impurities in crystals and glasses mainly depends on the order of the decay process, with lower order processes leading to more rapid relaxation (a behavior that is known under the term {open_quotes}gap-law{close_quotes}). Here we present measurements that contradict this assumption. Using high intensity psec pulses of the Stanford FEL we measured the relaxation rate of the SD vibrational stretch mode (at a frequency of 1800 cm) by applying a pump-probe technique. We find relaxation rates on the order of 2x10{sup 9} sec{sup -1}, which are a factor of 2 lower than those found for the isotope molecule SH (at a frequency of about 2500 cm{sup - 1}) in the same host{sup 1}. We recall that the relaxation of the SD vibrational stretch mode is controlled by a lower order process as compared to the SH molecule, which is due to the smaller number of host vibrational quanta to match the energy of the stretch mode; a fact we have confirmed experimentally by temperature dependent relaxation measurements. Thus our remits are in marked contrast to the so-called {open_quotes}Gap-Law{close_quotes} and emphasize the importance of the molecule - host coupling in the relaxation dynamics.

  7. The long and the short of it: SD1 polymorphism and the evolution of growth trait divergence in U.S. weedy rice.

    PubMed

    Reagon, Michael; Thurber, Carrie S; Olsen, Kenneth M; Jia, Yulin; Caicedo, Ana L

    2011-09-01

    Growth-related traits, such as greater height, greater biomass, faster growth rate and early flowering, are thought to enhance competitiveness of agricultural weeds. However, weedy rice, a conspecific weed of cultivated rice (Oryza sativa L.), displays variation for growth traits. In the United States, separately evolved weedy rice groups have been shown to share genomic identity with exotic domesticated cultivars. Through a common garden experiment, we investigated whether growth trait divergence has occurred among U.S. weeds and their putative cultivated progenitors. We also determined polymorphism patterns in the growth candidate gene, SD1, to assess its possible role in the evolution of divergent phenotypes. We found considerable growth trait variation among weed groups, suggesting that growth trait convergence is not evident among weedy populations. Phenotypic divergence of weedy rice from cultivated ancestors is most apparent for flowering time. Introgression of a chromosomal block containing the SD1 allele from tropical japonica, the predominant U.S. rice cultivar, was detected in one weedy rice population and is associated with a change in growth patterns in this group. This study demonstrates the role of introgressive hybridization in evolutionary divergence of an important weed. PMID:21854475

  8. Mn(II) Oxidation Is Catalyzed by Heme Peroxidases in “Aurantimonas manganoxydans” Strain SI85-9A1 and Erythrobacter sp. Strain SD-21▿

    PubMed Central

    Anderson, C. R.; Johnson, H. A.; Caputo, N.; Davis, R. E.; Torpey, J. W.; Tebo, B. M.

    2009-01-01

    A new type of manganese-oxidizing enzyme has been identified in two alphaproteobacteria, “Aurantimonas manganoxydans” strain SI85-9A1 and Erythrobacter sp. strain SD-21. These proteins were identified by tandem mass spectrometry of manganese-oxidizing bands visualized by native polyacrylamide gel electrophoresis in-gel activity assays and fast protein liquid chromatography-purified proteins. Proteins of both alphaproteobacteria contain animal heme peroxidase and hemolysin-type calcium binding domains, with the 350-kDa active Mn-oxidizing protein of A. manganoxydans containing stainable heme. The addition of both Ca2+ ions and H2O2 to the enriched protein from Aurantimonas increased manganese oxidation activity 5.9-fold, and the highest activity recorded was 700 μM min−1 mg−1. Mn(II) is oxidized to Mn(IV) via an Mn(III) intermediate, which is consistent with known manganese peroxidase activity in fungi. The Mn-oxidizing protein in Erythrobacter sp. strain SD-21 is 225 kDa and contains only one peroxidase domain with strong homology to the first 2,000 amino acids of the peroxidase protein from A. manganoxydans. The heme peroxidase has tentatively been named MopA (manganese-oxidizing peroxidase) and sheds new light on the molecular mechanism of Mn oxidation in prokaryotes. PMID:19411418

  9. Analysis of helium-rich subdwarf O stars. 1: NLTE models, methods, and fits for 21 Palomar Green survey sdOs

    NASA Technical Reports Server (NTRS)

    Thejll, P.; Bauer, F.; Saffer, R.; Liebert, J.; Kunze, D.; Shipman, H. L.

    1994-01-01

    Atmospheric parameters for 21 helium-rich hot subdwarf O stars from the Palomar Green survey are found from fits of non-local thermodynamic equilibrium (NLTE) models to optical spectra. About 250 new NLTE models in the parameter range T(sub eff) from 35,000 to 65,000 K, log (g) from 4.0 to 6.5, and epsilon(He) from 50% He to 99% He have been calculated. A fit for each object is presented. Estimated distances and luminosities are calculated, assuming a mass of 0.5 solar masses. Large distances above the Galactic plane are found, and this implies that the majority of the sdO stars belong to a different stellar population than the sdB, planetary nebulae and white dwarf stars. Possibilities may include the halo and a 'thick disk.' Kinematical data from the literature are also discussed in view of the found distances. Five of the stars have been observed, modeled, and analyzed by Dreizler et al., and significant differences exist between their results and ours for these stars. The reason for these differences is not yet known, but the problem does not alter the conclusions about population membership that we present.

  10. THE ROMER DELAY AND MASS RATIO OF THE sdB+dM BINARY 2M 1938+4603 FROM KEPLER ECLIPSE TIMINGS

    SciTech Connect

    Barlow, Brad N.; Wade, Richard A.; Liss, Sandra E.

    2012-07-10

    The eclipsing binary system 2M 1938+4603 consists of a pulsating hot subdwarf B star and a cool M dwarf companion in an effectively circular three-hour orbit. The light curve shows both primary and secondary eclipses, along with a strong reflection effect from the cool companion. Here, we present constraints on the component masses and eccentricity derived from the Romer delay of the secondary eclipse. Using six months of publicly available Kepler photometry obtained in short-cadence mode, we fit model profiles to the primary and secondary eclipses to measure their centroid values. We find that the secondary eclipse arrives on average 2.06 {+-} 0.12 s after the midpoint between primary eclipses. Under the assumption of a circular orbit, we calculate from this time delay a mass ratio of q = 0.2691 {+-} 0.0018 and individual masses of M{sub sd} = 0.372 {+-} 0.024 M{sub Sun} and M{sub c} = 0.1002 {+-} 0.0065 M{sub Sun} for the sdB and M dwarf, respectively. These results differ slightly from those of a previously published light-curve modeling solution; this difference, however, may be reconciled with a very small eccentricity, ecos {omega} Almost-Equal-To 0.00004. We also report a decrease in the orbital period of P-dot = (-1.23 {+-} 0.07) Multiplication-Sign 10{sup -10}.

  11. Benefits of utilizing CellProfiler as a characterization tool for U-10Mo nuclear fuel

    DOE PAGES

    Collette, R.; Douglas, J.; Patterson, L.; Bahun, G.; King, J.; Keiser, D.; Schulthess, J.

    2015-05-01

    Automated image processing techniques have the potential to aid in the performance evaluation of nuclear fuels by eliminating judgment calls that may vary from person-to-person or sample-to-sample. Analysis of in-core fuel performance is required for design and safety evaluations related to almost every aspect of the nuclear fuel cycle. This study presents a methodology for assessing the quality of uranium-molybdenum fuel images and describes image analysis routines designed for the characterization of several important microstructural properties. The analyses are performed in CellProfiler, an open-source program designed to enable biologists without training in computer vision or programming to automatically extract cellularmore » measurements from large image sets. The quality metric scores an image based on three parameters: the illumination gradient across the image, the overall focus of the image, and the fraction of the image that contains scratches. The metric presents the user with the ability to ‘pass’ or ‘fail’ an image based on a reproducible quality score. Passable images may then be characterized through a separate CellProfiler pipeline, which enlists a variety of common image analysis techniques. The results demonstrate the ability to reliably pass or fail images based on the illumination, focus, and scratch fraction of the image, followed by automatic extraction of morphological data with respect to fission gas voids, interaction layers, and grain boundaries.« less

  12. Benefits of utilizing CellProfiler as a characterization tool for U-10Mo nuclear fuel

    SciTech Connect

    Collette, R.; Douglas, J.; Patterson, L.; Bahun, G.; King, J.; Keiser, D.; Schulthess, J.

    2015-05-01

    Automated image processing techniques have the potential to aid in the performance evaluation of nuclear fuels by eliminating judgment calls that may vary from person-to-person or sample-to-sample. Analysis of in-core fuel performance is required for design and safety evaluations related to almost every aspect of the nuclear fuel cycle. This study presents a methodology for assessing the quality of uranium-molybdenum fuel images and describes image analysis routines designed for the characterization of several important microstructural properties. The analyses are performed in CellProfiler, an open-source program designed to enable biologists without training in computer vision or programming to automatically extract cellular measurements from large image sets. The quality metric scores an image based on three parameters: the illumination gradient across the image, the overall focus of the image, and the fraction of the image that contains scratches. The metric presents the user with the ability to ‘pass’ or ‘fail’ an image based on a reproducible quality score. Passable images may then be characterized through a separate CellProfiler pipeline, which enlists a variety of common image analysis techniques. The results demonstrate the ability to reliably pass or fail images based on the illumination, focus, and scratch fraction of the image, followed by automatic extraction of morphological data with respect to fission gas voids, interaction layers, and grain boundaries.

  13. Aqueous processing of U-10Mo scrap for high performance research reactor fuel

    NASA Astrophysics Data System (ADS)

    Youker, Amanda J.; Stepinski, Dominique C.; Maggos, Laura E.; Bakel, Allen J.; Vandegrift, George F.

    2012-08-01

    The Global Threat Reduction Initiative (GTRI) Conversion program, which is part of the US government's National Nuclear Security Administration (NNSA), supports the conversion of civilian use of highly enriched uranium (HEU) to low enriched uranium (LEU) for reactor fuel and targets. The reason for conversion is to eliminate the use of any material that may pose a threat to the United States or other foreign countries. High performance research reactors (HPRRs) cannot make the conversion to a standard LEU fuel because they require a more dense fuel to meet their performance requirements. As a result, a more dense fuel consisting of a monolithic uranium-molybdenum alloy containing 10% (w/w) Mo with Al cladding and a Zr bonding-layer is being considered. Significant losses are expected in the fabrication of this fuel, so a means to recycle the scrap pieces is needed. Argonne National Laboratory has developed an aqueous-processing flowsheet for scrap recovery in the fuel fabrication process for high-density LEU-monolithic fuel based on data found in the literature. Experiments have been performed to investigate dissolution conditions for solutions containing approximately 20 g-U/L and 50 g-U/L with and without Fe(NO3)3. HNO3 and HF concentrations have been optimized for timely dissolution of the fuel scrap and prevention of the formation of the U-Zr2 intermetallic, explosive complex, while meeting the requirements needed for further processing.

  14. EVALUATION OF U10MO FUEL PLATE IRRADIATION BEHAVIOR VIA NUMERICAL AND EXPERIMENTAL BENCHMARKING

    SciTech Connect

    Samuel J. Miller; Hakan Ozaltun

    2012-11-01

    This article analyzes dimensional changes due to irradiation of monolithic plate-type nuclear fuel and compares results with finite element analysis of the plates during fabrication and irradiation. Monolithic fuel plates tested in the Advanced Test Reactor (ATR) at Idaho National Lab (INL) are being used to benchmark proposed fuel performance for several high power research reactors. Post-irradiation metallographic images of plates sectioned at the midpoint were analyzed to determine dimensional changes of the fuel and the cladding response. A constitutive model of the fabrication process and irradiation behavior of the tested plates was developed using the general purpose commercial finite element analysis package, Abaqus. Using calculated burn-up profiles of irradiated plates to model the power distribution and including irradiation behaviors such as swelling and irradiation enhanced creep, model simulations allow analysis of plate parameters that are either impossible or infeasible in an experimental setting. The development and progression of fabrication induced stress concentrations at the plate edges was of primary interest, as these locations have a unique stress profile during irradiation. Additionally, comparison between 2D and 3D models was performed to optimize analysis methodology. In particular, the ability of 2D and 3D models account for out of plane stresses which result in 3-dimensional creep behavior that is a product of these components. Results show that assumptions made in 2D models for the out-of-plane stresses and strains cannot capture the 3-dimensional physics accurately and thus 2D approximations are not computationally accurate. Stress-strain fields are dependent on plate geometry and irradiation conditions, thus, if stress based criteria is used to predict plate behavior (as opposed to material impurities, fine micro-structural defects, or sharp power gradients), unique 3D finite element formulation for each plate is required.

  15. Protein kinase C and P2Y12 take center stage in thrombin-mediated activation of mammalian target of rapamycin complex 1 in human platelets

    PubMed Central

    Moore, S F; Hunter, R W; Hers, I

    2014-01-01

    Background Rapamycin, an inhibitor of mammalian target of rapamycin complex-1 (mTORC1), reduces platelet spreading, thrombus stability, and clot retraction. Despite an important role of mTORC1 in platelet function, little is known about how it is regulated. The objective of this study was to determine the signaling pathways that regulate mTORC1 in human platelets. Methods Mammalian target of rapamycin complex-1 activation was assessed by measuring the phosphorylation of its downstream substrate ribosomal S6 kinase 1 (p70S6K). Results Thrombin or the protein kinase C (PKC) activator phorbal 12-myristate 13-acetate stimulated activation of mTORC1 in a PKC-dependent, Akt-independent manner that correlated with phosphorylation of tuberin/tuberous sclerosis 2 (TSC2) (Ser939 and Thr1462). In contrast, insulin-like growth factor 1 (IGF-1)–stimulated TSC2 phosphorylation was completely dependent on phosphoinositide 3 kinase (PI3 kinase)/Akt but did not result in any detectable mTORC1 activation. Early (Ser939 and Thr1462) and late (Thr1462) TSC2 phosphorylation in response to thrombin were directly PKC dependent, whereas later TSC2 (Ser939) and p70S6K phosphorylation were largely dependent on paracrine signaling through P2Y12. PKC-mediated adenosine diphosphate (ADP) secretion was essential for thrombin-stimulated mTORC1 activation, as (i) ADP rescued p70S6K phosphorylation in the presence of a PKC inhibitor and (ii) P2Y12 antagonism prevented thrombin-mediated mTORC1 activation. Rescue of mTORC1 activation with exogenous ADP was completely dependent on the Src family kinases but independent of PI3 kinase/Akt. Interestingly, although inhibition of Src blocked the ADP rescue, it had little effect on thrombin-stimulated p70S6K phosphorylation under conditions where PKC was not inhibited. Conclusion These results demonstrate that thrombin activates the mTORC1 pathway in human platelets through PKC-mediated ADP secretion and subsequent activation of P2Y12, in a manner

  16. B{sub s(d)}-B{sub s(d)} mixing constraints on flavor changing decays of t and b quarks

    SciTech Connect

    Faessler, Amand; Gutsche, Thomas; Lyubovitskij, Valery E.; Kovalenko, Sergey; Schmidt, Ivan

    2010-10-01

    We study those dimension 6 effective operators which generate flavor-changing quark-gluon transitions of the third generation quarks, with t{yields}g+u(c) and b{yields}g+d(s), and which could be of interest for LHC experiments. We analyze the contribution of these operators to B{sub s(d)}-B{sub s(d)} mixing and derive limits on the corresponding effective couplings from the existing experimental data. The standard model gauge invariance relates these couplings to the couplings controlling t{yields}g+u(c). On this basis we derive upper limits for the branching ratios of these processes. We further show that forthcoming LHC experiments might be able to probe the studied operators and the physics beyond the standard model related to them.

  17. Modified protocol for in vivo imaging of wild-type mouse retina with customized miniature spectral domain optical coherence tomography (SD-OCT) device

    PubMed Central

    2012-01-01

    This protocol outlines and evaluates a modified scanning procedure for a customized spectral domain optical coherence tomography (SD-OCT) imaging apparatus within the wild-type C57Bl/6 mouse posterior segment. This modified protocol allows for the capture of a 50 degree field of view spanning 3 mm by 3 mm perimeter with the optic disc as the central point. By utilizing this scanning protocol a more reliable measurement of retinal thickness can be achieved outside the fluctuating region of the optic disc. This protocol, when applied to this high resolution device, enables non-invasive in vivo histological imaging and biometric assessment of the various layers of the rodent posterior segment within a 20 – 30 min procedural time-frame. This protocol could establish a standardized method for evaluating morphological changes, with this commercial SDOCT device, when assessing longitudinal disease pathophysiology and treatment response in mouse models for future vision science research. PMID:23057840

  18. Aspewentins D-H, 20-Nor-isopimarane Derivatives from the Deep Sea Sediment-Derived Fungus Aspergillus wentii SD-310.

    PubMed

    Li, Xiao-Dong; Li, Xiao-Ming; Li, Xin; Xu, Gang-Ming; Liu, Yang; Wang, Bin-Gui

    2016-05-27

    Five new 20-nor-isopimarane diterpenoids, aspewentins D-H (1-5), along with a related known congener, aspewentin A (6), were isolated from the culture extract of Aspergillus wentii SD-310, a fungal strain obtained from a deep-sea sediment sample. The structures of these compounds were established on the basis of spectroscopic interpretation, and the absolute configurations of compounds 1-5 were determined by X-ray crystallographic analysis and TDDFT-ECD calculations. The isolated compounds were evaluated for antimicrobial activity against nine human and aquatic pathogenic bacteria and four plant pathogenic fungi as well as for lethality against brine shrimp (Artemia salina). 20-Nor-isopimarane derivatives rarely occur in fungi, and only three (aspewentins A-C) have previously been reported from a marine-derived fungus. PMID:27148955

  19. Electron-capture and β-decay Rates for sd-Shell Nuclei in Stellar Environments Relevant to High-density O-Ne-Mg Cores

    NASA Astrophysics Data System (ADS)

    Suzuki, Toshio; Toki, Hiroshi; Nomoto, Ken'ichi

    2016-02-01

    Electron-capture and β-decay rates for nuclear pairs in the sd-shell are evaluated at high densities and high temperatures relevant to the final evolution of electron-degenerate O-Ne-Mg cores of stars with initial masses of 8-10 M⊙. Electron capture induces a rapid contraction of the electron-degenerate O-Ne-Mg core. The outcome of rapid contraction depends on the evolutionary changes in the central density and temperature, which are determined by the competing processes of contraction, cooling, and heating. The fate of the stars is determined by these competitions, whether they end up with electron-capture supernovae or Fe core-collapse supernovae. Since the competing processes are induced by electron capture and β-decay, the accurate weak rates are crucially important. The rates are obtained for pairs with A = 20, 23, 24, 25, and 27 by shell-model calculations in the sd-shell with the USDB Hamiltonian. Effects of Coulomb corrections on the rates are evaluated. The rates for pairs with A = 23 and 25 are important for nuclear Urca processes that determine the cooling rate of the O-Ne-Mg core, while those for pairs with A = 20 and 24 are important for the core contraction and heat generation rates in the core. We provide these nuclear rates at stellar environments in tables with fine enough meshes at various densities and temperatures for studies of astrophysical processes sensitive to the rates. In particular, the accurate rate tables are crucially important for the final fates of not only O-Ne-Mg cores but also a wider range of stars, such as C-O cores of lower-mass stars.

  20. An experimental study on use of 7T MRI for evaluation of myocardial infarction in SD rats transfected with pcDNA 3.1(+)/VEGF121 plasmid

    PubMed Central

    Zhang, Yan; Tian, Ruiqing; Shen, Xiangchun; Chen, Yushu; Chen, Wei; Gan, Lu; Shen, Guiquan; Ju, Haiyue; Yang, Li; Gao, Fabao

    2016-01-01

    This study aims to build the myocardial infarction model in SD rats transfected with pcDNA 3.1(+)/VEGF121 plasmid and study the effect of the transfection using 7T MRI. Twenty-four male SD rats were randomly divided into 2 groups, pcDNA 3.1(+)/VEGF121 plasmid transfection group (with improved coronary perfusion delivery) and myocardial infarction model group. Cardiac cine magnetic resonance imaging (Cine-MRI), T2-mapping and late gadolinium enhancement (LGE) cardiac imaging were performed at 24 h, 48 h, 72 h and 7 d after myocardial infarction, respectively. The signal intensity, area at risk (AAR), myocardium infarction core (MIC) and salvageable myocardial zone (SMZ) were compared. The hearts were harvested for anatomic characterization, which was related to pathological examination (TTC staining, HE staining, Masson staining and immunohistochemical staining). The Cine-MRI results showed that pcDNA 3.1(+)/VEGF121 plasmid transfection group had higher end-diastolic volume (EDV) with a reduction in MIC and SMZ, as compared with the myocardial infarction model group. MIC, SMZ and AAR of the plasmid transfection declined over time. At 7 d, the two groups did not differ significantly in AAR and T2 value. According to Western Blotting, VEGF was up-regulated, while CaSR and caspase-3 were downregulated in the plasmid transfection group, as compared with the model group. In conclusion, a good treatment effect was achieved by coronary perfusion of pcDNA 3.1(+)/VEGF121 plasmid. 7T CMR sequences provide a non-invasive quantification of the treatment efficacy. However, the assessment of myocardial injury using T2 value and AAR in the presence of edema is less accurate. The myocardial protection of the plasmid transfection group may be related to the inhibition of myocardial apoptosis, vascular endothelial cell (VEC) proliferation and collagen proliferation. The CaSR signaling pathway may contribute to reversing the apoptosis. PMID:27648128

  1. Rapid, accurate, and non-invasive measurement of zebrafish axial length and other eye dimensions using SD-OCT allows longitudinal analysis of myopia and emmetropization.

    PubMed

    Collery, Ross F; Veth, Kerry N; Dubis, Adam M; Carroll, Joseph; Link, Brian A

    2014-01-01

    Refractive errors in vision can be caused by aberrant axial length of the eye, irregular corneal shape, or lens abnormalities. Causes of eye length overgrowth include multiple genetic loci, and visual parameters. We evaluate zebrafish as a potential animal model for studies of the genetic, cellular, and signaling basis of emmetropization and myopia. Axial length and other eye dimensions of zebrafish were measured using spectral domain-optical coherence tomography (SD-OCT). We used ocular lens and body metrics to normalize and compare eye size and relative refractive error (difference between observed retinal radial length and controls) in wild-type and lrp2 zebrafish. Zebrafish were dark-reared to assess effects of visual deprivation on eye size. Two relative measurements, ocular axial length to body length and axial length to lens diameter, were found to accurately normalize comparisons of eye sizes between different sized fish (R2=0.9548, R2=0.9921). Ray-traced focal lengths of wild-type zebrafish lenses were equal to their retinal radii, while lrp2 eyes had longer retinal radii than focal lengths. Both genetic mutation (lrp2) and environmental manipulation (dark-rearing) caused elongated eye axes. lrp2 mutants had relative refractive errors of -0.327 compared to wild-types, and dark-reared wild-type fish had relative refractive errors of -0.132 compared to light-reared siblings. Therefore, zebrafish eye anatomy (axial length, lens radius, retinal radius) can be rapidly and accurately measured by SD-OCT, facilitating longitudinal studies of regulated eye growth and emmetropization. Specifically, genes homologous to human myopia candidates may be modified, inactivated or overexpressed in zebrafish, and myopia-sensitizing conditions used to probe gene-environment interactions. Our studies provide foundation for such investigations into genetic contributions that control eye size and impact refractive errors.

  2. Development of a Rat Schematic Eye From In Vivo Biometry and the Correction of Lateral Magnification in SD-OCT Imaging

    PubMed Central

    Lozano, Diana C.; Twa, Michael D.

    2013-01-01

    Purpose. Optical magnification in optical coherence tomography (OCT) depends on ocular biometric parameters (e.g., axial length). Biometric differences between eyes will influence scan location. A schematic model eye was developed to compensate for lateral magnification in OCT images of the healthy rat. Methods. Spectral-domain optical coherence tomography images were acquired in 19 eyes of 19 brown Norway rats. Images were scaled using the OCT instrument's built-in scaling function and by calculating the micron per degree from schematic model eyes developed from in vivo biometry (immersion A-scan and videokeratometry). Mean total retinal thickness was measured 500 μm away from the optic nerve head and optic nerve head diameter was measured. Corneal curvature, lens thickness, and axial length were modified to calculate their effects on OCT scan location and total retinal thickness. Results. Mean total retinal thickness increased by 21 μm and the SD doubles when images were scaled with the Built-in scaling (222 ± 13 μm) compared with scaling with individual biometric parameters (201 ± 6 μm). Optic nerve head diameter was three times larger when images were scaled with the Built-in scaling (925 ± 97 μm) than the individual biometric parameters (300 ± 27 μm). Assuming no other change in biometric parameters, total retinal thickness would decrease by 37 μm for every millimeter increase in anterior chamber depth due to changes in ocular lateral magnification and associated change in scan location. Conclusions. Scaling SD-OCT images with schematic model eyes derived from individual biometric data is important. This approach produces estimates of retinal thickness and optic nerve head size that are in good agreement with previously reported measurements. PMID:23989191

  3. Rapid, Accurate, and Non-Invasive Measurement of Zebrafish Axial Length and Other Eye Dimensions Using SD-OCT Allows Longitudinal Analysis of Myopia and Emmetropization

    PubMed Central

    Collery, Ross F.; Veth, Kerry N.; Dubis, Adam M.; Carroll, Joseph; Link, Brian A.

    2014-01-01

    Refractive errors in vision can be caused by aberrant axial length of the eye, irregular corneal shape, or lens abnormalities. Causes of eye length overgrowth include multiple genetic loci, and visual parameters. We evaluate zebrafish as a potential animal model for studies of the genetic, cellular, and signaling basis of emmetropization and myopia. Axial length and other eye dimensions of zebrafish were measured using spectral domain-optical coherence tomography (SD-OCT). We used ocular lens and body metrics to normalize and compare eye size and relative refractive error (difference between observed retinal radial length and controls) in wild-type and lrp2 zebrafish. Zebrafish were dark-reared to assess effects of visual deprivation on eye size. Two relative measurements, ocular axial length to body length and axial length to lens diameter, were found to accurately normalize comparisons of eye sizes between different sized fish (R2 = 0.9548, R2 = 0.9921). Ray-traced focal lengths of wild-type zebrafish lenses were equal to their retinal radii, while lrp2 eyes had longer retinal radii than focal lengths. Both genetic mutation (lrp2) and environmental manipulation (dark-rearing) caused elongated eye axes. lrp2 mutants had relative refractive errors of −0.327 compared to wild-types, and dark-reared wild-type fish had relative refractive errors of −0.132 compared to light-reared siblings. Therefore, zebrafish eye anatomy (axial length, lens radius, retinal radius) can be rapidly and accurately measured by SD-OCT, facilitating longitudinal studies of regulated eye growth and emmetropization. Specifically, genes homologous to human myopia candidates may be modified, inactivated or overexpressed in zebrafish, and myopia-sensitizing conditions used to probe gene-environment interactions. Our studies provide foundation for such investigations into genetic contributions that control eye size and impact refractive errors. PMID:25334040

  4. An experimental study on use of 7T MRI for evaluation of myocardial infarction in SD rats transfected with pcDNA 3.1(+)/VEGF121 plasmid.

    PubMed

    Zhang, Yan; Tian, Ruiqing; Shen, Xiangchun; Chen, Yushu; Chen, Wei; Gan, Lu; Shen, Guiquan; Ju, Haiyue; Yang, Li; Gao, Fabao

    2016-01-01

    This study aims to build the myocardial infarction model in SD rats transfected with pcDNA 3.1(+)/VEGF121 plasmid and study the effect of the transfection using 7T MRI. Twenty-four male SD rats were randomly divided into 2 groups, pcDNA 3.1(+)/VEGF121 plasmid transfection group (with improved coronary perfusion delivery) and myocardial infarction model group. Cardiac cine magnetic resonance imaging (Cine-MRI), T2-mapping and late gadolinium enhancement (LGE) cardiac imaging were performed at 24 h, 48 h, 72 h and 7 d after myocardial infarction, respectively. The signal intensity, area at risk (AAR), myocardium infarction core (MIC) and salvageable myocardial zone (SMZ) were compared. The hearts were harvested for anatomic characterization, which was related to pathological examination (TTC staining, HE staining, Masson staining and immunohistochemical staining). The Cine-MRI results showed that pcDNA 3.1(+)/VEGF121 plasmid transfection group had higher end-diastolic volume (EDV) with a reduction in MIC and SMZ, as compared with the myocardial infarction model group. MIC, SMZ and AAR of the plasmid transfection declined over time. At 7 d, the two groups did not differ significantly in AAR and T2 value. According to Western Blotting, VEGF was up-regulated, while CaSR and caspase-3 were downregulated in the plasmid transfection group, as compared with the model group. In conclusion, a good treatment effect was achieved by coronary perfusion of pcDNA 3.1(+)/VEGF121 plasmid. 7T CMR sequences provide a non-invasive quantification of the treatment efficacy. However, the assessment of myocardial injury using T2 value and AAR in the presence of edema is less accurate. The myocardial protection of the plasmid transfection group may be related to the inhibition of myocardial apoptosis, vascular endothelial cell (VEC) proliferation and collagen proliferation. The CaSR signaling pathway may contribute to reversing the apoptosis. PMID:27648128

  5. An experimental study on use of 7T MRI for evaluation of myocardial infarction in SD rats transfected with pcDNA 3.1(+)/VEGF121 plasmid

    PubMed Central

    Zhang, Yan; Tian, Ruiqing; Shen, Xiangchun; Chen, Yushu; Chen, Wei; Gan, Lu; Shen, Guiquan; Ju, Haiyue; Yang, Li; Gao, Fabao

    2016-01-01

    This study aims to build the myocardial infarction model in SD rats transfected with pcDNA 3.1(+)/VEGF121 plasmid and study the effect of the transfection using 7T MRI. Twenty-four male SD rats were randomly divided into 2 groups, pcDNA 3.1(+)/VEGF121 plasmid transfection group (with improved coronary perfusion delivery) and myocardial infarction model group. Cardiac cine magnetic resonance imaging (Cine-MRI), T2-mapping and late gadolinium enhancement (LGE) cardiac imaging were performed at 24 h, 48 h, 72 h and 7 d after myocardial infarction, respectively. The signal intensity, area at risk (AAR), myocardium infarction core (MIC) and salvageable myocardial zone (SMZ) were compared. The hearts were harvested for anatomic characterization, which was related to pathological examination (TTC staining, HE staining, Masson staining and immunohistochemical staining). The Cine-MRI results showed that pcDNA 3.1(+)/VEGF121 plasmid transfection group had higher end-diastolic volume (EDV) with a reduction in MIC and SMZ, as compared with the myocardial infarction model group. MIC, SMZ and AAR of the plasmid transfection declined over time. At 7 d, the two groups did not differ significantly in AAR and T2 value. According to Western Blotting, VEGF was up-regulated, while CaSR and caspase-3 were downregulated in the plasmid transfection group, as compared with the model group. In conclusion, a good treatment effect was achieved by coronary perfusion of pcDNA 3.1(+)/VEGF121 plasmid. 7T CMR sequences provide a non-invasive quantification of the treatment efficacy. However, the assessment of myocardial injury using T2 value and AAR in the presence of edema is less accurate. The myocardial protection of the plasmid transfection group may be related to the inhibition of myocardial apoptosis, vascular endothelial cell (VEC) proliferation and collagen proliferation. The CaSR signaling pathway may contribute to reversing the apoptosis.

  6. Multimodal Segmentation of Optic Disc and Cup From SD-OCT and Color Fundus Photographs Using a Machine-Learning Graph-Based Approach.

    PubMed

    Miri, Mohammad Saleh; Abràmoff, Michael D; Lee, Kyungmoo; Niemeijer, Meindert; Wang, Jui-Kai; Kwon, Young H; Garvin, Mona K

    2015-09-01

    In this work, a multimodal approach is proposed to use the complementary information from fundus photographs and spectral domain optical coherence tomography (SD-OCT) volumes in order to segment the optic disc and cup boundaries. The problem is formulated as an optimization problem where the optimal solution is obtained using a machine-learning theoretical graph-based method. In particular, first the fundus photograph is registered to the 2D projection of the SD-OCT volume. Three in-region cost functions are designed using a random forest classifier corresponding to three regions of cup, rim, and background. Next, the volumes are resampled to create radial scans in which the Bruch's Membrane Opening (BMO) endpoints are easier to detect. Similar to in-region cost function design, the disc-boundary cost function is designed using a random forest classifier for which the features are created by applying the Haar Stationary Wavelet Transform (SWT) to the radial projection image. A multisurface graph-based approach utilizes the in-region and disc-boundary cost images to segment the boundaries of optic disc and cup under feasibility constraints. The approach is evaluated on 25 multimodal image pairs from 25 subjects in a leave-one-out fashion (by subject). The performances of the graph-theoretic approach using three sets of cost functions are compared: 1) using unimodal (OCT only) in-region costs, 2) using multimodal in-region costs, and 3) using multimodal in-region and disc-boundary costs. Results show that the multimodal approaches outperform the unimodal approach in segmenting the optic disc and cup.

  7. Multimodal Segmentation of Optic Disc and Cup from SD-OCT and Color Fundus Photographs Using a Machine-Learning Graph-Based Approach

    PubMed Central

    Miri, Mohammad Saleh; Abràmoff, Michael D.; Lee, Kyungmoo; Niemeijer, Meindert; Wang, Jui-Kai; Kwon, Young H.

    2015-01-01

    In this work, a multimodal approach is proposed to use the complementary information from fundus photographs and spectral domain optical coherence tomography (SD-OCT) volumes in order to segment the optic disc and cup boundaries. The problem is formulated as an optimization problem where the optimal solution is obtained using a machine-learning theoretical graph-based method. In particular, first the fundus photograph is registered to the 2D projection of the SD-OCT volume. Three in-region cost functions are designed using a random forest classifier corresponding to three regions of cup, rim, and background. Next, the volumes are resampled to create radial scans in which the Bruch’s Membrane Opening (BMO) endpoints are easier to detect. Similar to in-region cost function design, the disc-boundary cost function is designed using a random forest classifier for which the features are created by applying the Haar Stationary Wavelet Transform (SWT) to the radial projection image. A multisurface graph-based approach utilizes the in-region and disc-boundary cost images to segment the boundaries of optic disc and cup under feasibility constraints. The approach is evaluated on 25 multimodal image pairs from 25 subjects in a leave-one-out fashion (by subject). The performances of the graph-theoretic approach using three sets of cost functions are compared: 1) using unimodal (OCT only) in-region costs, 2) using multimodal in-region costs, and 3) using multimodal in-region and disc-boundary costs. Results show that the multimodal approaches outperform the unimodal approach in segmenting the optic disc and cup. PMID:25781623

  8. Origin of Pressure-induced Superconducting Phase in KxFe2-ySe2 studied by Synchrotron X-ray Diffraction and Spectroscopy.

    PubMed

    Yamamoto, Yoshiya; Yamaoka, Hitoshi; Tanaka, Masashi; Okazaki, Hiroyuki; Ozaki, Toshinori; Takano, Yoshihiko; Lin, Jung-Fu; Fujita, Hidenori; Kagayama, Tomoko; Shimizu, Katsuya; Hiraoka, Nozomu; Ishii, Hirofumi; Liao, Yen-Fa; Tsuei, Ku-Ding; Mizuki, Jun'ichiro

    2016-01-01

    Pressure dependence of the electronic and crystal structures of KxFe2-ySe2, which has pressure-induced two superconducting domes of SC I and SC II, was investigated by x-ray emission spectroscopy and diffraction. X-ray diffraction data show that compressibility along the c-axis changes around 12 GPa, where a new superconducting phase of SC II appears. This suggests a possible tetragonal to collapsed tetragonal phase transition. X-ray emission spectroscopy data also shows the change in the electronic structure around 12 GPa. These results can be explained by the scenario that the two SC domes under pressure originate from the change of Fermi surface topology. Our results here show the pronounced increase of the density of states near the Fermi surface under pressure with a structural phase transition, which can help address our fundamental understanding for the appearance of the SC II phase.

  9. Origin of Pressure-induced Superconducting Phase in KxFe2-ySe2 studied by Synchrotron X-ray Diffraction and Spectroscopy.

    PubMed

    Yamamoto, Yoshiya; Yamaoka, Hitoshi; Tanaka, Masashi; Okazaki, Hiroyuki; Ozaki, Toshinori; Takano, Yoshihiko; Lin, Jung-Fu; Fujita, Hidenori; Kagayama, Tomoko; Shimizu, Katsuya; Hiraoka, Nozomu; Ishii, Hirofumi; Liao, Yen-Fa; Tsuei, Ku-Ding; Mizuki, Jun'ichiro

    2016-01-01

    Pressure dependence of the electronic and crystal structures of KxFe2-ySe2, which has pressure-induced two superconducting domes of SC I and SC II, was investigated by x-ray emission spectroscopy and diffraction. X-ray diffraction data show that compressibility along the c-axis changes around 12 GPa, where a new superconducting phase of SC II appears. This suggests a possible tetragonal to collapsed tetragonal phase transition. X-ray emission spectroscopy data also shows the change in the electronic structure around 12 GPa. These results can be explained by the scenario that the two SC domes under pressure originate from the change of Fermi surface topology. Our results here show the pronounced increase of the density of states near the Fermi surface under pressure with a structural phase transition, which can help address our fundamental understanding for the appearance of the SC II phase. PMID:27499373

  10. Electronic excitations and structure of Li{sub 2}IrO{sub 3} thin films grown on ZrO{sub 2}:Y (001) substrates

    SciTech Connect

    Jenderka, Marcus Schmidt-Grund, Rüdiger; Grundmann, Marius; Lorenz, Michael

    2015-01-14

    Thin films are a prerequisite for application of the emergent exotic ground states in iridates that result from the interplay of strong spin-orbit coupling and electronic correlations. We report on pulsed laser deposition of Li{sub 2}IrO{sub 3} films on ZrO{sub 2}:Y (001) single crystalline substrates. X-ray diffraction confirms preferential (001) and (10-1) out-of-plane crystalline orientations with well defined in-plane orientation. Resistivity between 35 and 300 K is dominated by a three-dimensional variable range hopping mechanism. The dielectric function is determined by means of spectroscopic ellipsometry and, complemented by Fourier transform infrared transmission spectroscopy, reveals a small optical gap of ≈300 meV, a splitting of the 5d-t{sub 2g} manifold, and several in-gap excitations attributed to phonons and possibly magnons.

  11. Large pinning forces and matching effects in YBa2Cu3O(7-δ) thin films with Ba2Y(Nb/Ta)O6 nano-precipitates.

    PubMed

    Opherden, Lars; Sieger, Max; Pahlke, Patrick; Hühne, Ruben; Schultz, Ludwig; Meledin, Alexander; Van Tendeloo, Gustaaf; Nast, Rainer; Holzapfel, Bernhard; Bianchetti, Marco; MacManus-Driscoll, Judith L; Hänisch, Jens

    2016-02-18

    The addition of mixed double perovskite Ba2Y(Nb/Ta)O6 (BYNTO) to YBa2Cu3O(7-δ) (YBCO) thin films leads to a large improvement of the in-field current carrying capability. For low deposition rates, BYNTO grows as well-oriented, densely distributed nanocolumns. We achieved a pinning force density of 25 GN/m(3) at 77 K at a matching field of 2.3 T, which is among the highest values reported for YBCO. The anisotropy of the critical current density shows a complex behavior whereby additional maxima are developed at field dependent angles. This is caused by a matching effect of the magnetic fields c-axis component. The exponent N of the current-voltage characteristics (inversely proportional to the creep rate S) allows the depinning mechanism to be determined. It changes from a double-kink excitation below the matching field to pinning-potential-determined creep above it.

  12. NMR characterization of sulphur substitution effects in the KxFe2-ySe2-zSz high-Tc superconductor

    DOE PAGES

    Torchetti, D. A.; Imai, T.; Lei, H. C.; Petrovic, C.

    2012-04-17

    We present a⁷⁷ Se NMR study of the effect of S substitution in the high-Tc superconductor KxFe2-ySe2-zSz in a temperature range up to 250 K. We examine two S concentrations, with z=0.8 (Tc~ 26 K) and z=1.6 (nonsuperconducting). The samples containing sulphur exhibit broader NMR line shapes than the KxFe₂Se₂ sample due to local disorder in the Se environment. Our Knight shift ⁷⁷K data indicate that in all samples, uniform spin susceptibility decreases with temperature, and that the magnitude of the Knight shift itself decreases with increased S concentration. In addition, S substitution progressively suppresses low-frequency spin fluctuations. None ofmore » the samples exhibit an enhancement of low-frequency antiferromagnetic spin fluctuations near Tc in 1/T₁T, as seen in FeSe.« less

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

    SciTech Connect

    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”).

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

    SciTech Connect

    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.

  15. Properties of fritless Ni0.6Cu0.4FeyMn2-yO4 NTC ceramic thick films

    NASA Astrophysics Data System (ADS)

    Jadhav, R. N.; Mathad, S. N.; Puri, Vijaya

    2013-06-01

    This paper reports a study on the microstructure, electrical and microwave properties of fritless thick films of Ni0.6Cu0.4FeyMn2-yO4 negative temperature coefficient (NTC) ceramic. Substitution of Fe has an important effect on the lattice parameter, x-ray density, thermistor constant and microwave properties in the GHz frequency range. The x-ray density increased linearly and the lattice parameter decreased with iron concentration. The Raman intensity mode around 720 cm-1 increased and shifted towards lower frequency with an increase in Fe content. The room temperature electrical resistivity of these thick films decreased from 2.8 to 0.37 MΩ cm and the microwave permittivity as well as absorption increased as the iron content increased.

  16. Initial steps in XY chromosome differentiation in Hoplias malabaricus and the origin of an X(1)X(2)Y sex chromosome system in this fish group.

    PubMed

    Cioffi, M B; Bertollo, L A C

    2010-12-01

    The neotropical fish, Hoplias malabaricus, is well known for its population-specific karyotypic diversity and the variation of its sex chromosomes. Seven karyomorphs (A to G) have been previously described with an XY, X(1)X(2)Y and XY(1)Y(2) sex chromosome system found in karyomorphs B, D and G, respectively. We compared the chromosomal characteristics of karyomorphs C and D using C-banding, staining with CMA(3) and DAPI, and by mapping the location of 18S rDNA, 5SHindIII-DNA and (TTAGGG)(n) repeat sequences. Our results show conserved karyotypes in both karyomorphs, a nascent XX/XY sex chromosome system in karyomorph C and the origin of neo-Y chromosome in karyomorph D. The X and Y chromosomes of karyomorph C differ only slightly because of the amplification of repetitive sequences on the X chromosome, resulting in a homomorphic condition in all females and a heteromorphic condition in all males examined. Our study showed that chromosomes X and 20 of karyomorph C have similar patterns to the X(1) and X(2) chromosomes of karyomorph D, and are probably homologous. We showed that the neo-Y chromosome of karyomorph D shares similar patterns to the chromosomes Y and 20 of karyomorph C, and probably evolved through tandem fusion between Ypter/20pter. An interstitial site of the satellite 5SHindIII-DNA on the neo-Y reinforces the hypothesized dicentric nature of this chromosome. Our study shows the initial steps in XY chromosome differentiation in H. malabaricus and, in a broader context, contributes to the understanding of the evolutionary pathway leading to a multiple X(1)X(2)Y sex chromosome system in fishes.

  17. Phase relations in KxFe2-ySe2 and the structure of superconducting KxFe2Se2 via high-resolution synchrotron diffraction

    NASA Astrophysics Data System (ADS)

    Shoemaker, Daniel P.; Chung, Duck Young; Claus, Helmut; Francisco, Melanie C.; Avci, Sevda; Llobet, Anna; Kanatzidis, Mercouri G.

    2012-11-01

    Superconductivity in iron selenides has experienced a rapid growth, but not without major inconsistencies in the reported properties. For alkali-intercalated iron selenides, even the structure of the superconducting phase is a subject of debate, in part because the onset of superconductivity is affected much more delicately by stoichiometry and preparation than in cuprate or pnictide superconductors. If high-quality, pure, superconducting intercalated iron selenides are ever to be made, the intertwined physics and chemistry must be explained by systematic studies of how these materials form and by and identifying the many coexisting phases. To that end, we prepared pure K2Fe4Se5 powder and superconductors in the KxFe2-ySe2 system, and examined differences in their structures by high-resolution synchrotron and single-crystal x-ray diffraction. We found four distinct phases: semiconducting K2Fe4Se5, a metallic superconducting phase KxFe2Se2 with x ranging from 0.38 to 0.58, the phase KFe1.6Se2 with full K occupancy and no Fe vacancy ordering, and a oxidized phase K0.51(5)Fe0.70(2)Se that forms the PbClF structure upon exposure to moisture. We find that the vacancy-ordered phase K2Fe4Se5 does not become superconducting by doping, but the distinct iron-rich minority phase KxFe2Se2 precipitates from single crystals upon cooling from above the vacancy ordering temperature. This coexistence of separate metallic and semiconducting phases explains a broad maximum in resistivity around 100 K. Further studies to understand the solubility of excess Fe in the KxFe2-ySe2 structure will shed light on the maximum fraction of superconducting KxFe2Se2 that can be obtained by solid state synthesis.

  18. Association of PON1, P2Y12 and COX1 with Recurrent Ischemic Events in Patients with Extracranial or Intracranial Stenting

    PubMed Central

    Wang, Bo; Sun, Shu-Sen; Gao, Feng; Mo, Da-Peng; Song, Li-Gang; Sun, Xuan; Liu, Lian; Zhao, Xing-Quan; Wang, Yi-Long; Wang, Yong-Jun; Zhao, Zhi-Gang; Miao, Zhong-Rong

    2016-01-01

    Background and Purpose Short-term combined use of clopidogrel and aspirin improves cerebrovascular outcomes in patients with symptomatic extracranial or intracranial stenosis. Antiplatelet non-responsiveness is related to recurrent ischemic events, but the culprit genetic variants responsible for the non-responsiveness have not been well studied. We aimed to identify the genetic variants associated with poor clinical outcomes. Methods Patients with symptomatic extracranial or intracranial stenosis scheduled for stenting and receiving dual antiplatelets (clopidogrel 75 mg and aspirin 100 mg daily) for at least 5 days before intervention were enrolled. Ischemic events including recurrent transient ischemic attack, stroke, myocardial infarction, and vascular-related mortality within 12 months follow-up were recorded. We examined the influence of genetic polymorphisms on treatment outcome in our patients. Results A total of 268 patients were enrolled into our study and ischemic events were observed in 39 patients. For rs662 of paraoxonase 1 (PON1), allele C was associated with an increased risk of ischemic events (OR = 1.64, 95%CI = 1.03–2.62, P = 0.029). The A-allele carriers of rs2046934 of P2Y12 had a significant association with adverse events (OR = 2.01, 95%CI = 1.10–3.67, P = 0.041). The variant T-allele of cyclooxygenase-1 (COX1) rs1330344 significantly increased the risk of recurrent clinical events (OR = 1.85, 95%CI = 1.12–3.03, P = 0.017). The other single nucleotide polymorphism (SNP) had no association with ischemic events. Conclusions PON1, P2Y12 and COX1 polymorphisms were associated with poorer vascular outcomes. Testing for these polymorphisms may be valuable in the identification of patients at risk for recurrent ischemic events. PMID:26870959

  19. Activation of a P2Y4-like purinoceptor triggers an increase in cytosolic [Ca2+] in the red blood cells of the lizard Ameiva ameiva (Squamata, Teiidae).

    PubMed

    Sartorello, R; Garcia, C R S

    2005-01-01

    An increasing number of pathophysiological roles for purinoceptors are emerging, some of which have therapeutic potential. Erythrocytes are an important source of purines, which can be released under physiological and physiopathological conditions, acting on purinergic receptors associated with the same cell or with neighboring cells. Few studies have been conducted on lizards, and have been limited to ATP agonist itself. We have previously shown that the red blood cells (RBCs) of the lizard Ameiva ameiva store Ca2+ in the endoplasmic reticulum (ER) and that the purinergic agonist ATP triggers a rapid and transient increase of [Ca2+]c by mobilization of the cation from internal stores. We also reported the ability of the second messenger IP3 to discharge the ER calcium pool of the ER. Here we characterize the purinoceptor present in the cytoplasmic membrane of the RBCs of the lizard Ameiva ameiva by the selective use of ATP analogues and pyrimidine nucleotides. The nucleotides UTP, UDP, GTP, and ATPgammaS triggered a dose-dependent response, while interestingly 2MeSATP, 2ClATP, alpha, ss-ATP, and ADP failed to do so in a 1- to 200-microm con- centration. The EC50 obtained for the compounds tested was 41.77 microM for UTP, 48.11 microM for GTP, 53.11 microM for UDP, and 30.78 microM for ATPgammaS. The present data indicate that the receptor within the RBCs of Ameiva ameiva is a P2Y4-like receptor due to its pharmacological similarity to the mammalian P2Y4 receptor. PMID:15665982

  20. Electronic structure and thermoelectric properties of (Mg2X)2 / (Mg2Y)2 (X, Y = Si, Ge, Sn) superlattices from first-principle calculations

    NASA Astrophysics Data System (ADS)

    Guo, San-Dong

    2016-05-01

    To identify thermoelectric materials containing abundant, low-cost and non-toxic elements, we have studied the electronic structures and thermoelectric properties of (Mg2X)2/ (Mg2Y)2 (X, Y = Si, Ge, Sn) superlattices with state-of-the-art first-principles calculations using a modified Becke and Johnson (mBJ) exchange potential. Our results show that (Mg2Ge)2/ (Mg2Sn)2 and (Mg2Si)2/ (Mg2Sn)2 are semi-metals using mBJ plus spin-orbit coupling (mBJ + SOC), while (Mg2Si)2/ (Mg2Ge)2 is predicted to be a direct-gap semiconductor with a mBJ gap value of 0.46 eV and mBJ + SOC gap value of 0.44 eV. Thermoelectric properties are predicted by through solving the Boltzmann transport equations within the constant scattering time approximation. It is found that (Mg2Si)2/ (Mg2Ge)2 has a larger Seebeck coefficient and power factor than (Mg2Ge)2/ (Mg2Sn)2 and (Mg2Si)2/ (Mg2Sn)2 for both p-type and n-type doping. The detrimental influence of SOC on the power factor of p-type (Mg2X)2/ (Mg2Y)2 (X, Y = Si, Ge, Sn) is analyzed as a function of the carrier concentration, but there is a negligible SOC effect for n-type. These results can be explained by the influence of SOC on their valence and conduction bands near the Fermi level.

  1. Formation mechanism of superconducting phase and its three-dimensional architecture in pseudo-single-crystal KxFe2-ySe2

    DOE PAGES

    Liu, Yong; Xing, Qingfeng; Straszheim, Warren E.; Marshman, Jeff; Pedersen, Pal; McLaughlin, Richard; Lograsso, Thomas A.

    2016-02-11

    Here, we report how the superconducting phase forms in pseudo-single-crystal KxFe2-ySe2. In situ scanning electron microscopy (SEM) observation reveals that, as an order-disorder transition occurs, on cooling, most of the high-temperature iron-vacancy-disordered phase gradually changes into the iron-vacancy-ordered phase whereas a small quantity of the high-temperature phase retains its structure and aggregates to the stripes with more iron concentration but less potassium concentration compared to the iron-vacancy-ordered phase. The stripes that are generally recognized as the superconducting phase are actually formed as a remnant of the high-temperature phase with a compositional change after an “imperfect” order-disorder transition. It should bemore » emphasized that the phase separation in pseudo-single-crystal KxFe2-ySe2 is caused by the iron-vacancy order-disorder transition. The shrinkage of the high-temperature phase and the expansion of the newly created iron-vacancy-ordered phase during the phase separation rule out the mechanism of spinodal decomposition proposed in an early report [Wang et al, Phys. Rev. B 91, 064513 (2015)]. Since the formation of the superconducting phase relies on the occurrence of the iron-vacancy order-disorder transition, it is impossible to synthesize a pure superconducting phase by a conventional solid state reaction or melt growth. By focused ion beam-scanning electron microscopy, we further demonstrate that the superconducting phase forms a contiguous three-dimensional architecture composed of parallelepipeds that have a coherent orientation relationship with the iron-vacancy-ordered phase.« less

  2. Formation mechanism of superconducting phase and its three-dimensional architecture in pseudo-single-crystal KxF e2 -yS e2

    NASA Astrophysics Data System (ADS)

    Liu, Yong; Xing, Qingfeng; Straszheim, Warren E.; Marshman, Jeff; Pedersen, Pal; McLaughlin, Richard; Lograsso, Thomas A.

    2016-02-01

    We report how the superconducting phase forms in pseudo-single-crystal KxF e2 -yS e2 . In situ scanning electron microscopy (SEM) observation reveals that, as an order-disorder transition occurs, on cooling, most of the high-temperature iron-vacancy-disordered phase gradually changes into the iron-vacancy-ordered phase, whereas a small quantity of the high-temperature phase retains its structure and aggregates to the stripes with more iron concentration but less potassium concentration compared to the iron-vacancy-ordered phase. The stripes that are generally recognized as the superconducting phase are actually formed as a remnant of the high-temperature phase with a compositional change after an "imperfect" order-disorder transition. It should be emphasized that the phase separation in pseudo-single-crystal KxF e2 -yS e2 is caused by the iron-vacancy order-disorder transition. The shrinkage of the high-temperature phase and the expansion of the newly created iron-vacancy-ordered phase during the phase separation rule out the mechanism of spinodal decomposition proposed in an early report [Z. Wang et al., Phys. Rev. B 91, 064513 (2015), 10.1103/PhysRevB.91.064513]. Since the formation of the superconducting phase relies on the occurrence of the iron-vacancy order-disorder transition, it is impossible to synthesize a pure superconducting phase by a conventional solid state reaction or melt growth. By focused ion beam scanning electron microscopy, we further demonstrate that the superconducting phase forms a contiguous three-dimensional architecture composed of parallelepipeds that have a coherent orientation relationship with the iron-vacancy-ordered phase.

  3. Reading performance correlates with white-matter properties in preterm and term children

    PubMed Central

    Andrews, James S; Ben-Shachar, Michal; Yeatman, Jason D; Flom, Lynda L; Luna, Beatriz; Feldman, Heidi M

    2010-01-01

    Aim We used diffusion tensor imaging to investigate the association between white-matter integrity and reading ability in a cohort of 28 children. Nineteen preterm children (14 males, five females; mean age 11y 11mo [SD 1y 10mo], mean gestational age 30.5wks (SD 3.2), mean birthweight was 1455g [SD 625]); and nine term children (five males, four females; mean age 12y 8mo [SD 2y 5mo], mean gestational age 39.6 weeks (SD 1.2), and mean birthweight 3877g [SD 473]). Method We tested whether fractional anisotropy in a left hemisphere temporoparietal region and in the corpus callosum correlates with birthweight and scores on the following three subtests of the Woodcock-Johnson III Tests of Achievement: word identification, word attack, and passage comprehension. Results Preterm children had lower reading scores than a comparison group for all reading subtests (p<0.05). We found significant correlations between birthweight and fractional anisotropy in the whole corpus callosum (p=0.001), and between fractional anisotropy and reading skill in the genu (p=0.001) and body (p=0.001) of the corpus callosum. The correlation between reading skill and fractional anisotropy in a left temporoparietal region previously associated with reading disability was not significant (p=0.095). Interpretation We conclude that perinatal white-matter injury of the central corpus callosum may have long-term developmental implications for reading performance. PMID:19747208

  4. Narrowing the gap: from semiconductor to semimetal in the homologous series of rare-earth zinc arsenides RE(2-y)Zn4As4·n(REAs) and Mn-substituted derivatives RE(2-y)Mn(x)Zn(4-x)As4·n(REAs) (RE = La-Nd, Sm, Gd).

    PubMed

    Lin, Xinsong; Tabassum, Danisa; Mar, Arthur

    2015-12-14

    A homologous series of ternary rare-earth zinc arsenides, prepared by reactions of the elements at 750 °C, has been identified with the formula RE(2-y)Zn4As4·n(REAs) (n = 2, 3, 4) for various RE members. They adopt trigonal structures: RE(4-y)Zn4As6 (RE = La-Nd), space group R3̄m1, Z = 3; RE(5-y)Zn4As7 (RE = Pr, Nd, Sm, Gd), space group P3̄m1, Z = 1; RE(6-y)Zn4As8 (RE = La-Nd, Sm, Gd), space group R3̄m1, Z = 3. The Zn atoms can be partially substituted by Mn atoms, resulting in quaternary derivatives RE(2-y)Mn(x)Zn(4-x)As4·n(REAs). Single-crystal structures were determined for nine ternary and quaternary arsenides RE(2-y)M4As4·n(REAs) (M = Mn, Zn) as representative examples of these series. The structures are built by stacking close-packed nets of As atoms, sometimes in very long sequences, with RE atoms occupying octahedral sites and M atoms occupying tetrahedral sites, resulting in an intergrowth of [REAs] and [M2As2] slabs. The recurring feature of all members of the homologous series is a sandwich of [M2As2]-[REAs]-[M2As2] slabs, while rocksalt-type blocks of [REAs] increase in thickness between these sandwiches with higher n. Similar to the previously known related homologous series REM(2-x)As2·n(REAs) which is deficient in M, this new series RE(2-y)M4As4·n(REAs) exhibits deficiencies in RE to reduce the electron excess that would be present in the fully stoichiometric formulas. Enthalpic and entropic factors are considered to account for the differences in site deficiencies in these two homologous series. Band structure calculations indicate that the semiconducting behaviour of the parent n = 0 member (with CaAl2Si2-type structure) gradually evolves, through a narrowing of the gap between valence and conduction bands, to semimetallic behaviour as the number of [REAs] blocks increases, to the limit of n = ∞ for rocksalt-type REAs.

  5. Optimal timing of initiation of oral P2Y12-receptor antagonist therapy in patients with non-ST elevation acute coronary syndromes. Lessons learnt from the ACCOAST-trial.

    PubMed

    Zeymer, Uwe; Montalescot, Gilles; Ardissino, Diego; Bolognese, Leonardo; Clemmensen, Peter; Collet, Jean-Philippe; Lopez-Sendon, Jose; Widimsky, Petr

    2016-06-01

    The optimal time-point of the initiation of P2Y12 antagonist therapy in patients with non-ST elevation acute coronary syndromes (NTSE-ACS) is still a matter of debate. European guidelines recommend P2Y12 as soon as possible after first medical contact. However, the only trial which compared the two strategies did not demonstrate any benefit of pre-treatment with prasugrel before angiography compared to starting therapy after angiography and just prior to percutaneous coronary intervention (PCI). This paper summarizes the results of pharmacodynamic and previous studies, and gives recommendations for the initiation of P2Y12 antagonist therapy in NSTE-ACS in different clinical situations. PMID:25921481

  6. Acid evoked thermal hyperalgesia involves peripheral P2Y1 receptor mediated TRPV1 phosphorylation in a rodent model of thrombus induced ischemic pain

    PubMed Central

    2014-01-01

    Background We previously developed a thrombus-induced ischemic pain (TIIP) animal model, which was characterized by chronic bilateral mechanical allodynia without thermal hyperalgesia (TH). On the other hand we had shown that intraplantar injection of acidic saline facilitated ATP-induced pain, which did result in the induction of TH in normal rats. Because acidic pH and increased ATP are closely associated with ischemic conditions, this study is designed to: (1) examine whether acidic saline injection into the hind paw causes the development of TH in TIIP, but not control, animals; and (2) determine which peripheral mechanisms are involved in the development of this TH. Results Repeated intraplantar injection of pH 4.0 saline, but not pH 5.5 and 7.0 saline, for 3 days following TIIP surgery resulted in the development of TH. After pH 4.0 saline injections, protein levels of hypoxia inducible factor-1α (HIF-1α) and carbonic anhydrase II (CA II) were elevated in the plantar muscle indicating that acidic stimulation intensified ischemic insults with