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Sample records for 2x devices

  1. Manufacturability of 2x-nm devices with EUV tool

    NASA Astrophysics Data System (ADS)

    Tawarayama, Kazuo; Nakajima, Yumi; Kyoh, Suigen; Aoyama, Hajime; Matsunaga, Kentaro; Magoshi, Shunko; Tanaka, Satoshi; Hayashi, Yumi; Mori, Ichiro

    2011-04-01

    Due to the promising development status of EUVL as a practical lithography technology for the 2x-nm node, we are continuing to evaluate its process liability using the EUV1 at Selete, which has an Off-Axis illumination capability. The resolution limit of the EUV1 for L&S patterns is currently 18 nm for dipole illumination, and 16 nm for aggressive dipole illumination. This study examined the critical points of EUVL for device manufacturing through wafer processes. The yield obtained from electrical measurements indicates the maturity of the technology, including the resist process, the tool, and the mask. Optimization of the resist and RIE processes significantly improved the yield. The final yields obtained from electrical measurements were 100% for hp 30 nm, 70% for hp 28 nm, and 40% for hp 26 nm. These results demonstrate EUV lithography to be a practical technology that is now suitable for 2x nm semiconductor manufacture.

  2. High performance nonvolatile memory devices based on Cu2-xSe nanowires

    NASA Astrophysics Data System (ADS)

    Wu, Chun-Yan; Wu, Yi-Liang; Wang, Wen-Jian; Mao, Dun; Yu, Yong-Qiang; Wang, Li; Xu, Jun; Hu, Ji-Gang; Luo, Lin-Bao

    2013-11-01

    We report on the rational synthesis of one-dimensional Cu2-xSe nanowires (NWs) via a solution method. Electrical analysis of Cu2-xSe NWs based memory device exhibits a stable and reproducible bipolar resistive switching behavior with a low set voltage (0.3-0.6 V), which can enable the device to write and erase data efficiently. Remarkably, the memory device has a record conductance switching ratio of 108, much higher than other devices ever reported. At last, a conducting filaments model is introduced to account for the resistive switching behavior. The totality of this study suggests that the Cu2-xSe NWs are promising building blocks for fabricating high-performance and low-consumption nonvolatile memory devices.

  3. La2-xSrxCuO4 superconductor nanowire devices

    DOE PAGES

    Litombe, N. E.; Bollinger, A. T.; Hoffman, J. E.; ...

    2014-07-02

    La2-xSrxCuO₄ nanowire devices have been fabricated and characterized using electrical transport measurements. In addition, nanowires with widths down to 80 nm are patterned using high-resolution electron beam lithography. However, the narrowest nanowires show incomplete superconducting transitions with some residual resistance at T = 4 K. Here, we report on refinement of the fabrication process to achieve narrower nanowire devices with complete superconducting transitions, opening the path to the study of novel physics arising from dimension-limited superconductivity on the nanoscale.

  4. MEMS/ECD Method for Making Bi(2-x)Sb(x)Te3 Thermoelectric Devices

    NASA Technical Reports Server (NTRS)

    Lim, James; Huang, Chen-Kuo; Ryan, Margaret; Snyder, G. Jeffrey; Herman, Jennifer; Fleurial, Jean-Pierre

    2008-01-01

    A method of fabricating Bi(2-x)Sb(x)Te3-based thermoelectric microdevices involves a combination of (1) techniques used previously in the fabrication of integrated circuits and of microelectromechanical systems (MEMS) and (2) a relatively inexpensive MEMS-oriented electrochemical-deposition (ECD) technique. The present method overcomes the limitations of prior MEMS fabrication techniques and makes it possible to satisfy requirements.

  5. Anomalous elastic properties of RF-sputtered amorphous TeO2+x thin film for temperature-stable SAW device applications.

    PubMed

    Dewan, Namrata; Sreenivas, Kondepudy; Gupta, Vinay

    2008-03-01

    The anomalous elastic properties of TeO2+x thin films deposited by rf diode sputtering on substrates at room temperature have been studied. The deposited films are amorphous, and IR spectroscopy reveals the formation of Te-O bond. X-ray photoelectron spectroscopy confirms the variation in the stoichiometry of TeO2+x film from x=0 to 1 with an increase in the oxygen percentage in processing gas composition. The elastic parameters of the films in comparison to the reported values for TeO2+x single crystal are found to be low. However, the temperature coefficients of elastic parameters of all deposited films exhibit anomalous behavior showing positive values for TC(C11) in the range (32.0 to 600.0)x10(-4) degrees C(-1) and TC(C44)=(35.0 to 645.5)x10(-4) degrees C(-1) against the negative values TC(C11)=-2.7x10(-4) degrees C(-1) and TC(C44)=-0.73x10(-4) degrees C(-1) reported for TeO2+x single crystal. The variation in the elastic parameters and their temperature coefficients is correlated with the change in the three-dimensional network of Te-O bonding. The anomalous elastic properties of the TeO2+x films grown in 100% O2 are useful for potential application in the design of temperature stable surface acoustic wave devices.

  6. The effect of oxygen vacancies on the electrical properties of TiO2-x Re-RAM switching devices

    NASA Astrophysics Data System (ADS)

    Benkraouda, Maamar

    2014-03-01

    The main goal of this work is to contribute toward an accurate determination of the electronic properties of Resistance random access memory (Re-RAM) using the density functional theory, which is the current state of the art method that employs high accuracy, it can treat a few hundred atoms on medium sized PC. All the fundamental properties are studied as a function of the mole fraction. The density of states arising from vacancy distribution, the electron transport and formation energy are analyzed. Using controllable mole fraction, various intermediate resistance states are induced. Oxygen vacancy has a considerable effect on the electrical properties of most transition metal oxides such as TiOx Re-RAM devices. The presence of oxygen vacancies is linked to the on-state conduction and resistance switching mechanism. Hydrogen is a ubiquitous impurity in most semiconductors, insertion of hydrogen atoms will remove some of defect states which were induced by oxygen vacancies; this will obviously have an effect on the conductive path, because hydrogen in the vacancy site results in the rupture of conductive channel by localizing electrons, the conductivity may decrease in this case.

  7. Assessing internal contamination after the detonation of a radiological dispersion device using a 2x2-inch sodium iodide detector.

    PubMed

    Dewji, S; Hertel, N; Ansari, A

    2013-07-01

    The detonation of a radiological dispersion device may result in a situation where individuals inhale radioactive materials and require rapid assessment of internal contamination. The feasibility of using a 2×2-inch sodium-iodide detector to determine the committed effective dose to an individual following acute inhalation of gamma-emitting radionuclides was investigated. Experimental configurations of point sources with a polymethyl methacrylate slab phantom were used to validate Monte Carlo simulations. The validated detector model was used to simulate the responses for four detector positions on six different anthropomorphic phantoms. The nuclides examined included (241)Am, (60)Co, (137)Cs, (131)I and (192)Ir. Biokinetic modelling was employed to determine the distributed activity in the body as a function of post-inhalation time. The simulation and biokinetic data were used to determine time-dependent count-rate values at optimal detector locations on the body for each radionuclide corresponding to a target committed effective dose (E50) value of 250 mSv.

  8. Investigating the origins of high multilevel resistive switching in forming free Ti/TiO2-x-based memory devices through experiments and simulations

    NASA Astrophysics Data System (ADS)

    Bousoulas, P.; Giannopoulos, I.; Asenov, P.; Karageorgiou, I.; Tsoukalas, D.

    2017-03-01

    Although multilevel capability is probably the most important property of resistive random access memory (RRAM) technology, it is vulnerable to reliability issues due to the stochastic nature of conducting filament (CF) creation. As a result, the various resistance states cannot be clearly distinguished, which leads to memory capacity failure. In this work, due to the gradual resistance switching pattern of TiO2-x-based RRAM devices, we demonstrate at least six resistance states with distinct memory margin and promising temporal variability. It is shown that the formation of small CFs with high density of oxygen vacancies enhances the uniformity of the switching characteristics in spite of the random nature of the switching effect. Insight into the origin of the gradual resistance modulation mechanisms is gained by the application of a trap-assisted-tunneling model together with numerical simulations of the filament formation physical processes.

  9. Ising models on the 2 x 2 x {infinity} lattices

    SciTech Connect

    Yurishchev, M. A.

    2007-03-15

    Exact analytic solutions are presented for two 2 x 2 x {infinity} Ising etageres. The first model has a simple cubic lattice with fully anisotropic interactions. The second model consists of two different types of linear chains and includes noncrossing diagonal bonds on the side faces of the 2 x 2 x {infinity} parallelepiped. In both cases, the solutions are expressed through square radicals and obtained by using the obvious symmetry of the Hamiltonians, Z{sub 2} x C{sub 2v}, and the hidden algebraic {lambda}{lambda} symmetry of the transfer matrix secular equations. The solution found for the second model is used to analyze the behavior of specific heat in a frustrated many-chain system.

  10. J-2X Engine Tested at Stennis

    NASA Video Gallery

    Another key component of NASA's new Space Launch System, the J-2X rocket engine, is put to a 500-second firing test at NASA's Stennis Space Center on Nov. 9 The J-2X rocket engine will help carry t...

  11. P2X Receptors as Drug Targets

    PubMed Central

    Jarvis, Michael F.

    2013-01-01

    The study of P2X receptors has long been handicapped by a poverty of small-molecule tools that serve as selective agonists and antagonists. There has been progress, particularly in the past 10 years, as cell-based high-throughput screening methods were applied, together with large chemical libraries. This has delivered some drug-like molecules in several chemical classes that selectively target P2X1, P2X3, or P2X7 receptors. Some of these are, or have been, in clinical trials for rheumatoid arthritis, pain, and cough. Current preclinical research programs are studying P2X receptor involvement in pain, inflammation, osteoporosis, multiple sclerosis, spinal cord injury, and bladder dysfunction. The determination of the atomic structure of P2X receptors in closed and open (ATP-bound) states by X-ray crystallography is now allowing new approaches by molecular modeling. This is supported by a large body of previous work using mutagenesis and functional expression, and is now being supplemented by molecular dynamic simulations and in silico ligand docking. These approaches should lead to P2X receptors soon taking their place alongside other ion channel proteins as therapeutically important drug targets. PMID:23253448

  12. J-2X: Back in the Saddle

    NASA Video Gallery

    A J-2X power pack assembly burns brightly during a hot fire test Nov. 27 at NASA's Stennis Space Center in Mississippi. Engineers pulled the assembly from the test stand in September to install add...

  13. NASA Continues J-2X Powerpack Testing

    NASA Video Gallery

    NASA conducted a long duration test of the J-2X powerpack, 340 seconds total, at the Stennis Space Center in southern Mississippi on May 10, marking another step in SLS development, the next-genera...

  14. J-2X Turbopump Cavitation Diagnostics

    NASA Technical Reports Server (NTRS)

    Santi, I. Michael; Butas, John P.; Tyler, Thomas R., Jr.; Aguilar, Robert; Sowers, T. Shane

    2010-01-01

    The J-2X is the upper stage engine currently being designed by Pratt & Whitney Rocketdyne (PWR) for the Ares I Crew Launch Vehicle (CLV). Propellant supply requirements for the J-2X are defined by the Ares Upper Stage to J-2X Interface Control Document (ICD). Supply conditions outside ICD defined start or run boxes can induce turbopump cavitation leading to interruption of J-2X propellant flow during hot fire operation. In severe cases, cavitation can lead to uncontained engine failure with the potential to cause a vehicle catastrophic event. Turbopump and engine system performance models supported by system design information and test data are required to predict existence, severity, and consequences of a cavitation event. A cavitation model for each of the J-2X fuel and oxidizer turbopumps was developed using data from pump water flow test facilities at Pratt & Whitney Rocketdyne (PWR) and Marshall Space Flight Center (MSFC) together with data from Powerpack 1A testing at Stennis Space Center (SSC) and from heritage systems. These component models were implemented within the PWR J-2X Real Time Model (RTM) to provide a foundation for predicting system level effects following turbopump cavitation. The RTM serves as a general failure simulation platform supporting estimation of J-2X redline system effectiveness. A study to compare cavitation induced conditions with component level structural limit thresholds throughout the engine was performed using the RTM. Results provided insight into system level turbopump cavitation effects and redline system effectiveness in preventing structural limit violations. A need to better understand structural limits and redline system failure mitigation potential in the event of fuel side cavitation was indicated. This paper examines study results, efforts to mature J-2X turbopump cavitation models and structural limits, and issues with engine redline detection of cavitation and the use of vehicle-side abort triggers to augment the

  15. Scanning Tunneling Microscopy of SILICON(100) 2 X 1

    NASA Astrophysics Data System (ADS)

    Hubacek, Jerome S.

    1992-01-01

    The Si(100) 2 x 1 surface, a technologically important surface in microelectronics and silicon molecular beam epitaxy (MBE), has been studied with the scanning tunneling microscope (STM) to attempt to clear up the controversy that surrounds previous studies of this surface. To this end, an ultra-high vacuum (UHV) STM/surface science system has been designed and constructed to study semiconductor surfaces. Clean Si(100) 2 x 1 surfaces have been prepared and imaged with the STM. Atomic resolution images probing both the filled states and empty states indicate that the surface consists of statically buckled dimer rows. With electronic device dimensions shrinking to smaller and smaller sizes, the Si-SiO_2 interface is becoming increasingly important and, although it is the most popular interface used in the microelectronics industry, little is known about the initial stages of oxidation of the Si(100) surface. Scanning tunneling microscopy has been employed to examine Si(100) 2 x 1 surfaces exposed to molecular oxygen in UHV. Ordered rows of bright and dark spots, rotated 45^circ from the silicon dimer rows, appear in the STM images, suggesting that the Si(100)-SiO_2 interface may be explained with a beta -cristobalite(100) structure rotated by 45^ circ on the Si(100) surface.

  16. Final J-2X Test of 2011

    NASA Video Gallery

    NASA conducted its final J-2X rocket engine test of the year Dec. 14, the 10th firing in a series of tests on the new upper-stage engine that will carry humans farther into space than ever before. ...

  17. J-2X Powerpack Completes Testing

    NASA Video Gallery

    The J-2X powerpack assembly was fired up one last time on Dec. 13 at NASA’s Stennis Space Center in Mississippi, finishing a year of testing on an important component of America’s next heavy-li...

  18. NMR probe of pseudogap characteristics in CaAl2-xSi2+x

    NASA Astrophysics Data System (ADS)

    Lue, C. S.; Wang, S. Y.; Fang, C. P.

    2007-06-01

    We report the results of a Al27 nuclear magnetic resonance (NMR) study of CaAl2-xSi2+x , near the stoichiometric composition with x=0 . The low-temperature NMR relaxation rates for stoichiometric (x=0) and nonstoichiometric ( x=-0.1 and 0.1) compounds follow a Korringa law, associated with a finite density of carriers at the Fermi level. High-temperature relaxation rates for x⩾0 go over to a semiconductorlike activated form, providing information about the electronic structure near the Fermi energy. The results are consistent with pseudogap features identified by recent band-structure calculations. An analysis of the pseudogap change vs composition further points out that the band-filling picture is proper for the understanding of the NMR observations in CaAl2-xSi2+x .

  19. Entanglement monogamy inequality in a 2 x 2 x 4 system

    SciTech Connect

    Ren Xijun; Jiang Wei

    2010-02-15

    In this report, we show explicitly that the tangles of an arbitrary pure state in a 2 x 2 x 4 system satisfy the monogamy relation. This relation is also generalized to mixed states. As the tangle is always larger than the square of the concurrence, our result implies that the monogamy relation holds for concurrence too. It also supports the idea that the tangle could qualify as an elementary bipartite entanglement measure.

  20. Enhanced bolometric properties of TiO2-x thin films by thermal annealing

    NASA Astrophysics Data System (ADS)

    Ashok Kumar Reddy, Y.; Shin, Young Bong; Kang, In-Ku; Lee, Hee Chul; Sreedhara Reddy, P.

    2015-07-01

    The effect of thermal annealing on the bolometric properties of TiO2-x films was investigated. The test-patterned TiO2-x samples were annealed at 300 °C temperature in order to enhance their structural and electrical properties for effective infrared image sensor device applications. The crystallinity was changed from amorphous to rutile/anatase in annealed TiO2-x films. Compared to the as-deposited samples, a decrement of the band gap and a decrease of the electrical resistivity were perceived in annealed samples. We found that the annealed samples show linear current-voltage (I-V) characteristic performance, which implies that ohmic contact was well formed at the interface between the TiO2-x and the Ti electrode. Moreover, the annealed TiO2-x sample had a significantly low 1/f noise parameter (1.21 × 10-13) with a high bolometric parameter (β) value compared to those of the as-deposited samples. As a result, the thermal annealing process can be used to prepare TiO2-x film for a high-performance bolometric device.

  1. Oxygen diffusion in UO2+x and (U,Pu)O2+-x

    SciTech Connect

    Andersson, Anders D.; Liu, Xiang-Yang

    2012-05-03

    In the first part of this report we revisit an earlier study of oxygen diffusion in UO{sub 2+x}, in which we used density functional theory (DFT) calculations to parameterize a kinetic Monte Carlo (kMC) model. The results from these earlier kMC simulations are reproduced in Fig. 1 and they indicate fairly good agreement with available experiments. This work was later expanded to include a larger temperature range. However, since the publication of this study there have been a number of advancements in DFT methodology for UO{sub 2} and UO{sub 2+x} providing increased accuracy. We have also gained better understanding of the oxygen clustering phenomena occurring in UO{sub 2+x}. For these two reasons, the DFT calculations of the migration barriers of single oxygen interstitials and di-interstitial clusters have been repeated using the LDA+U and GGA+U methodologies. The earlier study used regular GGA and, even though this method captures similar trends as the more advanced LDA+U and GGA+U techniques, it does not fulfill the quantitative requirements set by some applications. Additionally, we have identified a mechanism for the most stable quad-interstitial clusters to migrate and here we calculate the corresponding barriers within both the LDA+U and GGA+U methodologies. The new LDA+U and GGA+U data sets are analyzed in terms of available experiments. In the second part of this report we present initial results for the impact of Pu on oxygen diffusion in UO{sub 2}. The first step in understanding this process is to calculate the binding energies of oxygen vacancies and interstitials to a Pu ion in the UO{sub 2} matrix. Possible diffusion mechanisms are discussed for (U,Pu)O{sub 2-x}, (U,Pu)O{sub 2} and (U,Pu)O{sub 2+x}.

  2. Imaging P2X4 receptor subcellular distribution, trafficking, and regulation using P2X4-pHluorin.

    PubMed

    Xu, Ji; Chai, Hua; Ehinger, Konstantin; Egan, Terrance M; Srinivasan, Rahul; Frick, Manfred; Khakh, Baljit S

    2014-07-01

    P2X4 receptors are adenosine triphosphate (ATP)-gated cation channels present on the plasma membrane (PM) and also within intracellular compartments such as vesicles, vacuoles, lamellar bodies (LBs), and lysosomes. P2X4 receptors in microglia are up-regulated in epilepsy and in neuropathic pain; that is to say, their total and/or PM expression levels increase. However, the mechanisms underlying up-regulation of microglial P2X4 receptors remain unclear, in part because it has not been possible to image P2X4 receptor distribution within, or trafficking between, cellular compartments. Here, we report the generation of pH-sensitive fluorescently tagged P2X4 receptors that permit evaluations of cell surface and total receptor pools. Capitalizing on information gained from zebrafish P2X4.1 crystal structures, we designed a series of mouse P2X4 constructs in which a pH-sensitive green fluorescent protein, superecliptic pHluorin (pHluorin), was inserted into nonconserved regions located within flexible loops of the P2X4 receptor extracellular domain. One of these constructs, in which pHluorin was inserted after lysine 122 (P2X4-pHluorin123), functioned like wild-type P2X4 in terms of its peak ATP-evoked responses, macroscopic kinetics, calcium flux, current-voltage relationship, and sensitivity to ATP. P2X4-pHluorin123 also showed pH-dependent fluorescence changes, and was robustly expressed on the membrane and within intracellular compartments. P2X4-pHluorin123 identified cell surface and intracellular fractions of receptors in HEK-293 cells, hippocampal neurons, C8-B4 microglia, and alveolar type II (ATII) cells. Furthermore, it showed that the subcellular fractions of P2X4-pHluorin123 receptors were cell and compartment specific, for example, being larger in hippocampal neuron somata than in C8-B4 cell somata, and larger in C8-B4 microglial processes than in their somata. In ATII cells, P2X4-pHluorin123 showed that P2X4 receptors were secreted onto the PM when LBs

  3. P2X3 Receptors and Sensory Transduction

    NASA Astrophysics Data System (ADS)

    Kennedy, Charles

    It has been known for many years that exogenously administered adenosine 5 -triphosphate (ATP) evokes acute pain, but the physiological and pathophysiological roles of endogenous ATP in nociceptive signalling are only now becoming clear. ATP produces its effects through P2X and P2Y receptors, and the P2X3 receptor is of notable importance. It shows a selective expression, at high levels in nociceptive sensory neurons, where it forms functional receptors on its own and in combination with the P2X2 receptor. Recent studies have used gene knockout methods, antisense oligonucleotides, small interfering RNA technologies, and a novel selective P2X3 antagonist, A-317491, to show that P2X3 receptors play a prominent role in both chronic inflammatory and neuropathic pain. Several other P2X subunits also appear to be expressed in sensory neurons and there is evidence for functional P2X1/5 or P2X2/6 heteromers in some of these. These data indicate that P2X receptors, particularly the P2X3 subtype, could be targetted in the search for new, effective analgesics.

  4. ATP induces P2X7 receptor-independent cytokine and chemokine expression through P2X1 and P2X3 receptors in murine mast cells.

    PubMed

    Bulanova, Elena; Budagian, Vadim; Orinska, Zane; Koch-Nolte, Friedrich; Haag, Friedrich; Bulfone-Paus, Silvia

    2009-04-01

    Extracellular ATP mediates a diverse array of biological responses in many cell types and tissues, including immune cells. We have demonstrated that ATP induces purinergic receptor P2X(7) mediated membrane permeabilization, apoptosis, and cytokine expression in murine mast cells (MCs). Here, we report that MCs deficient in the expression of the P2X(7) receptor are resistant to the ATP-induced membrane permeabilization and apoptosis. However, ATP affects the tyrosine phosphorylation pattern of P2X(7)knockout cells, leading to the activation of ERK1/2. Furthermore, ATP induces expression of several cytokines and chemokines in these cells, including IL-4, IL-6, IFN-gamma, TNF-alpha, RANTES, and MIP-2, at the mRNA level. In addition, the release of IL-6 and IL-13 to cell-conditioned medium was confirmed by ELISA. The ligand selectivity and pharmacological profile indicate the involvement of two P2X family receptors, P2X(1) and P2X(3). Thus, depending on genetic background, particular tissue microenvironment, and ATP concentration, MCs can presumably engage different P2X receptor subtypes, which may result in functionally distinct biological responses to extracellular nucleotides. This finding highlights a novel level of complexity in the sophisticated biology of MCs and may facilitate the development of new therapeutic approaches to modulate MC activities.

  5. Bolometric properties of reactively sputtered TiO2-x films for thermal infrared image sensors

    NASA Astrophysics Data System (ADS)

    Reddy, Y. Ashok Kumar; Kang, In-Ku; Shin, Young Bong; Lee, Hee Chul

    2015-09-01

    A heat-sensitive layer (TiO2-x ) was successfully deposited by RF reactive magnetron sputtering for infrared (IR) image sensors at different relative mass flow of oxygen gas (R O2) levels. The deposition rate was decreased with an increase in the percentage of R O2 from 3.4% to 3.7%. TiO2-x samples deposited at room temperature exhibited amorphous characteristics. Oxygen deficiency causes a change in the oxidation state and is assumed to decrease the Ti4+ component on the surfaces of TiO2-x films. The oxygen stoichiometry (x) in TiO2-x films decreased from 0.35 to 0.05 with increasing the R O2 level from 3.4% to 3.7%, respectively. In TiO2-x -test-patterned samples, the resistivity decreased with the temperature, confirming the typical semiconducting property. The bolometric properties of the resistivity, temperature coefficient of resistance (TCR), and the flicker (1/ f) noise parameter were determined at different x values in TiO2-x samples. The rate of TCR dependency with regard to the 1/ f noise parameter is a universal bolometric parameter (β), acting as the dynamic element in a bolometer. It is high when a sample has a relatively low resistivity (0.82 Ω·cm) and a lower 1/ f noise parameter (3.16   ×   10-12). The results of this study indicate that reactively sputtered TiO2-x is a viable bolometric material for uncooled IR image sensor devices.

  6. The P2X7/P2X4 interaction shapes the purinergic response in murine macrophages.

    PubMed

    Pérez-Flores, Gabriela; Lévesque, Sébastien A; Pacheco, Jonathan; Vaca, Luis; Lacroix, Steve; Pérez-Cornejo, Patricia; Arreola, Jorge

    2015-11-20

    The ATP-gated P2X4 and P2X7 receptors are cation channels, co-expressed in excitable and non-excitable cells and play important roles in pain, bone development, cytokine release and cell death. Although these receptors interact the interacting domains are unknown and the functional consequences of this interaction remain unclear. Here we show by co-immunoprecipitation that P2X4 interacts with the C-terminus of P2X7 and by fluorescence resonance energy transfer experiments that this receptor-receptor interaction is driven by ATP. Furthermore, disrupting the ATP-driven interaction by knocking-out P2X4R provoked an attenuation of P2X7-induced cell death, dye uptake and IL-1β release in macrophages. Thus, P2X7 interacts with P2X4 via its C-terminus and disrupting the P2X7/P2X4 interaction hinders physiological responses in immune cells.

  7. Ion Implant Enabled 2x Lithography

    NASA Astrophysics Data System (ADS)

    Martin, Patrick M.; Godet, Ludovic; Cheung, Andrew; de Cock, Gael; Hatem, Chris

    2011-01-01

    Ion implantation has many applications in microelectronics beyond doping. The broad range of species available combined with the ability to precisely control dose, angle, and energy offers compelling advantages for use in precision material modification. The application to lithography has been reported elsewhere. Integrating ion implantation into the lithography process enables scaling the feature size requirements beyond the 15 nm node with a simplified double patterning sequence. In addition, ion implant may be used to remove line edge roughness, providing tremendous advantages to meet extreme lithography imaging requirements and provide additional device stability. We examine several species (e.g. Si, Ar, etc.) and the effect of energy and impact angle on several commercially available 193 nm immersion photoresists using a Varian VIISta® single wafer high current ion implanter. The treated photoresist will be evaluated for stability in an integrated double patterning application with ion implant used to freeze the primary image. We report on critical dimension impact, pattern integrity, optical property modification, and adhesion. We analyze the impact of line edge roughness improvement beyond the work of C. Struck including the power spectral distribution. TGA and FTIR Spectroscopy results for the implanted photoresist materials will also be included.

  8. P2X7 Receptors in Neurological and Cardiovascular Disorders

    PubMed Central

    Skaper, Stephen D.; Debetto, Patrizia; Giusti, Pietro

    2009-01-01

    P2X receptors are ATP-gated cation channels that mediate fast excitatory transmission in diverse regions of the brain and spinal cord. Several P2X receptor subtypes, including P2X7, have the unusual property of changing their ion selectivity during prolonged exposure to ATP, which results in a channel pore permeable to molecules as large as 900 daltons. The P2X7 receptor was originally described in cells of hematopoietic origin, and mediates the influx of Ca2+ and Na+ and Ca2+ and Na+ ions as well as the release of proinflammatory cytokines. P2X7 receptors may affect neuronal cell death through their ability to regulate the processing and release of interleukin-1β, a key mediator in neurodegeneration, chronic inflammation, and chronic pain. Activation of P2X7, a key mediator in neurodegeneration, chronic inflammation, and chronic pain. Activation of P2X7 receptors provides an inflammatory stimulus, and P2X7 receptor-deficient mice have substantially attenuated inflammatory responses, including models of neuropathic and chronic inflammatory pain. Moreover, P2X7 receptor activity, by regulating the release of proinflammatory cytokines, may be involved in the pathophysiology of depression. Apoptotic cell death occurs in a number of vascular diseases, including atherosclerosis, restenosis, and hypertension, and may be linked to the release of ATP from endothelial cells, P2X7 receptor activation, proinflammatory cytokine production, and endothelial cell apoptosis. In this context, the P2X7 receptor may be viewed as a gateway of communication between the nervous, immune, and cardiovascular systems. PMID:20029634

  9. Dynamic spin correlations in 'stuffed' spin ice Ho(2+x)Ti(2-x)O(7-d)

    SciTech Connect

    Ehlers, Georg

    2008-02-01

    The magnetic correlations in 'stuffed' spin ice Ho{sub 2+x}Ti{sub 2-x}O{sub 7-{delta}} have been characterized using quasielastic neutron scattering. At temperatures above 1K , these correlations are short ranged in nature and dynamic on a picosecond to nanosecond time scale. As for the case of pure spin ice Ho{sub 2+x}Ti{sub 2-x}O{sub 7}, one can identify, above the freezing temperature, a quantum relaxation regime which is enhanced as it persists to even higher temperatures, T{approx}30-40K , than in the parent compound.

  10. Decavanadate, a P2X receptor antagonist, and its use to study ligand interactions with P2X7 receptors.

    PubMed

    Michel, Anton D; Xing, Mengle; Thompson, Kyla M; Jones, Clare A; Humphrey, Patrick P A

    2006-03-18

    In this study we have studied decavanadate effects at P2X receptors. Decavanadate competitively blocked 2'- and 3'-O-(4benzoylbenzoyl) ATP (BzATP) stimulated ethidium accumulation in HEK293 cells expressing human recombinant P2X7 receptors (pK(B) 7.5). The effects of decavanadate were rapid (minutes) in both onset and offset and contrasted with the much slower kinetics of pyridoxal 5-phosphate (P5P), Coomassie brilliant blue (CBB) and 1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine (KN62). Decavanadate competitively blocked the slowly reversible, or irreversible, blockade of the P2X7 receptor produced by P5P and oxidised ATP suggesting competition for a common binding site. However, the interaction between decavanadate and KN62 was non-competitive. Decavanadate also blocked P2X2 and P2X4 receptors but with slightly lower potency. These data demonstrate that decavanadate is the first reversible and competitive antagonist of the P2X7 receptor and is a useful tool for studying the mechanism of interaction of ligands with the P2X7 receptor.

  11. Modulation of P2X3 and P2X2/3 Receptors by Monoclonal Antibodies.

    PubMed

    Shcherbatko, Anatoly; Foletti, Davide; Poulsen, Kris; Strop, Pavel; Zhu, Guoyun; Hasa-Moreno, Adela; Melton Witt, Jody; Loo, Carole; Krimm, Stellanie; Pios, Ariel; Yu, Jessica; Brown, Colleen; Lee, John K; Stroud, Robert; Rajpal, Arvind; Shelton, David

    2016-06-03

    Purinergic homomeric P2X3 and heteromeric P2X2/3 receptors are ligand-gated cation channels activated by ATP. Both receptors are predominantly expressed in nociceptive sensory neurons, and an increase in extracellular ATP concentration under pathological conditions, such as tissue damage or visceral distension, induces channel opening, membrane depolarization, and initiation of pain signaling. Hence, these receptors are considered important therapeutic targets for pain management, and development of selective antagonists is currently progressing. To advance the search for novel analgesics, we have generated a panel of monoclonal antibodies directed against human P2X3 (hP2X3). We have found that these antibodies produce distinct functional effects, depending on the homomeric or heteromeric composition of the target, its kinetic state, and the duration of antibody exposure. The most potent antibody, 12D4, showed an estimated IC50 of 16 nm on hP2X3 after short term exposure (up to 18 min), binding to the inactivated state of the channel to inhibit activity. By contrast, with the same short term application, 12D4 potentiated the slow inactivating current mediated by the heteromeric hP2X2/3 channel. Extending the duration of exposure to ∼20 h resulted in a profound inhibition of both homomeric hP2X3 and heteromeric hP2X2/3 receptors, an effect mediated by efficient antibody-induced internalization of the channel from the plasma membrane. The therapeutic potential of mAb12D4 was assessed in the formalin, complete Freund's adjuvant, and visceral pain models. The efficacy of 12D4 in the visceral hypersensitivity model indicates that antibodies against P2X3 may have therapeutic potential in visceral pain indications.

  12. J-2X Engine Test, May 16, 2012

    NASA Video Gallery

    The shake, rattle and roar lasted just seven seconds, but the short J-2X test conducted May 16 at NASA's John C. Stennis Space Center moved the space agency closer to a return to deep space. NASA o...

  13. Successful First J-2X Combustion Stability Test

    NASA Video Gallery

    NASA conducted a key stability test firing of the J-2X rocket engine Dec. 1, marking another step forward in development of the upper-stage engine that will carry humans farther into space than eve...

  14. Throttle Up! J-2X Powerpack Test Sets Record

    NASA Video Gallery

    During a record-breaking June 8 test, engineers throttled the J-2X powerpack up and down several times to explore numerous operating points required for the fuel and oxidizer turbopumps. The result...

  15. J-2X Nozzle Extension Goes the Distance

    NASA Video Gallery

    NASA engineers conducted a 550-second test of the new J-2X rocket engine at Stennis Space Center in Mississippi on July 13. The test, conducted on the A-2 Test Stand, continued a series of firings ...

  16. J-2X Test Articles Using FDM Process

    NASA Technical Reports Server (NTRS)

    Anderson, Ted; Ruf, Joe; Steele, Phil

    2010-01-01

    This viewgraph presentation gives a brief history of the J-2X engine, along with detailed description of the material demonstrator and test articles that were created using Fused Deposition Modeling (FDM) process.

  17. J-2X Engine Ready For Second Test Series

    NASA Video Gallery

    Time-lapse video of the installation of J-2X engine 10001 in the A-2 test-stand at Stennis, complete with clamshell assembly and nozzle extension. With these enhancements test engineers will measur...

  18. J-2X Rocket Engine, 40-Second Test

    NASA Video Gallery

    NASA conducted a 40-second test of the J-2X rocket engine Sept. 28, the most recent in a series of tests of the next-generation engine selected as part of the Space Launch System architecture that ...

  19. J-2X Powerpack Test, July 24, 2012

    NASA Video Gallery

    NASA engineers surpassed their previously set J-2X powerpack record at Stennis's Test Complex A with a 1,350-second test on July 24. In this video there are three aspects featured:the outside test ...

  20. Start Me Up! J-2X Rocket Test

    NASA Video Gallery

    NASA engineers conducted the first in a new round of tests on the next-generation J-2X rocket engine Feb. 15 at Stennis Space Center. The 35-second test continued progress in development of the eng...

  1. J-2X Engine Continues to Set Standards

    NASA Video Gallery

    Testing of the next-generation J-2X rocket engine continues to set standards. Last fall, the engine attained 100 percent power in just its fourth test and became the fastest U.S. rocket engine to a...

  2. J-2X Engine 'Goes the Distance' at Stennis

    NASA Video Gallery

    J-2X rocket engine testing continues at NASA's Stennis Space Center in Mississippi with the second in a series of tests conducted on Feb. 27. The 550-second, full-duration test provided critical in...

  3. Close Encounter With 'Fired Up' J-2X Engine

    NASA Video Gallery

    This video shows a spillway view of the 550-second, full-duration test of the J-2X engine on Feb. 27 at Stennis Space Center in Mississippi. Data from the test will provide critical information abo...

  4. J-2X Engine Test Goes Full Duration

    NASA Video Gallery

    NASA conducted a 260-second J-2X engine test at the Stennis Space Center in southern Mississippi on June 13 marking another step in developing the Space Launch System, the next-generation rocket th...

  5. J-2X Powerpack Test Lights Up the Sky

    NASA Video Gallery

    A burst of flame from a J-2X Powerpack test-firing lights up the sky on Dec. 5, 2012 at NASA's Stennis Space Center in Mississippi. For the first time, the Space Launch System team invited Twitter ...

  6. P2X7 receptors stimulate AKT phosphorylation in astrocytes

    PubMed Central

    Jacques-Silva, Maria C; Rodnight, Richard; Lenz, Guido; Liao, Zhongji; Kong, Qiongman; Tran, Minh; Kang, Yuan; Gonzalez, Fernando A; Weisman, Gary A; Neary, Joseph T

    2004-01-01

    Emerging evidence indicates that nucleotide receptors are widely expressed in the nervous system. Here, we present evidence that P2Y and P2X receptors, particularly the P2X7 subtype, are coupled to the phosphoinositide 3-kinase (PI3K)/Akt pathway in astrocytes. P2Y and P2X receptor agonists ATP, uridine 5′-triphosphate (UTP) and 2′,3′-O-(4-benzoyl)-benzoyl ATP (BzATP) stimulated Akt phosphorylation in primary cultures of rat cortical astrocytes. BzATP induced Akt phosphorylation in a concentration- and time-dependent manner, similar to the effect of BzATP on Akt phosphorylation in 1321N1 astrocytoma cells stably transfected with the rat P2X7 receptor. Activation was maximal at 5 – 10 min and was sustained for 60 min; the EC50 for BzATP was approximately 50 μM. In rat cortical astrocytes, the positive effect of BzATP on Akt phosphorylation was independent of glutamate release. The effect of BzATP on Akt phosphorylation in rat cortical astrocytes was significantly reduced by the P2X7 receptor antagonist Brilliant Blue G and the P2X receptor antagonist iso-pyridoxal-5′-phosphate-6-azophenyl-2′,4′-disulfonic acid, but was unaffected by trinitrophenyl-ATP, oxidized ATP, suramin and reactive blue 2. Results with specific inhibitors of signal transduction pathways suggest that extracellular and intracellular calcium, PI3K and a Src family kinase are involved in the BzATP-induced Akt phosphorylation pathway. In conclusion, our data indicate that stimulation of astrocytic P2X7 receptors, as well as other P2 receptors, leads to Akt activation. Thus, signaling by nucleotide receptors in astrocytes may be important in several cellular downstream effects related to the Akt pathway, such as cell cycle and apoptosis regulation, protein synthesis, differentiation and glucose metabolism. PMID:15023862

  7. Chemical pressure induced change in multiferroicity of Bi1+2xGd2x/2Fe1-2xO3 bulk ceramics

    NASA Astrophysics Data System (ADS)

    Pradhan, S. K.; Sahu, D. R.; Rout, P. P.; Das, S. K.; Pradhan, A. K.; Srinivasu, V. V.; Roul, B. K.

    2017-04-01

    We have optimized Gd ion substitution in BiFeO3 (BFO) and observed prominently change in structural, electrical and magnetic behavior of Bi1+2xGd2x/2Fe1-2xO3 ceramics synthesized through slow step sintering schedule. It is observed that with the increase in concentration of Gd (x=0.1), original structure of BFO is transformed from rhombohedral R3c space group to orthorhombic Pn21a space group. Surprisingly, unit cell volume is drastically contracted (35% for x=0.2) and the sintered specimen showed enhanced room temperature ferromagnetic behavior although the original BFO is normally G-type antiferromagnetic in nature at 643 K. It is expected that intrinsic chemical pressure within the bulk body built by the substitution of Gd in presence of excess bismuth greatly supported through unidirectional movement of electrical dipole moment with in each individual domain as a result of which suppression of leakage current with enhanced dielectric and ferroelectric hysteresis is observed.

  8. Checking 2xM quantum separability via semidefinite programming

    SciTech Connect

    Woerdeman, Hugo J.

    2003-01-01

    In this paper, we propose a sequence of tests which give a definitive test for checking 2xM separability. The test is definitive in the sense that each test corresponds to checking membership in a cone, and that the closure of the union of all these cones consists exactly of all 2xM separable states. Membership in each single cone may be checked via semidefinite programming, and is thus a tractable problem. This sequential test comes about by considering the dual problem, the characterization of all positive maps acting C{sup 2x2}{yields}C{sup MxM}. The latter in turn is solved by characterizing all positive quadratic matrix polynomials in a complex variable.

  9. Testing for the J-2X Upper Stage Engine

    NASA Technical Reports Server (NTRS)

    Buzzell, James C.

    2010-01-01

    NASA selected the J-2X Upper Stage Engine in 2006 to power the upper stages of the Ares I crew launch vehicle and the Ares V cargo launch vehicle. Based on the proven Saturn J-2 engine, this new engine will provide 294,000 pounds of thrust and a specific impulse of 448 seconds, making it the most efficient gas generator cycle engine in history. The engine's guiding philosophy emerged from the Exploration Systems Architecture Study (ESAS) in 2005. Goals established then called for vehicles and components based, where feasible, on proven hardware from the Space Shuttle, commercial, and other programs, to perform the mission and provide an order of magnitude greater safety. Since that time, the team has made unprecedented progress. Ahead of the other elements of the Constellation Program architecture, the team has progressed through System Requirements Review (SRR), System Design Review (SDR), Preliminary Design Review (PDR), and Critical Design Review (CDR). As of February 2010, more than 100,000 development engine parts have been ordered and more than 18,000 delivered. Approximately 1,300 of more than 1,600 engine drawings were released for manufacturing. A major factor in the J-2X development approach to this point is testing operations of heritage J-2 engine hardware and new J-2X components to understand heritage performance, validate computer modeling of development components, mitigate risk early in development, and inform design trades. This testing has been performed both by NASA and its J-2X prime contractor, Pratt & Whitney Rocketdyne (PWR). This body of work increases the likelihood of success as the team prepares for testing the J-2X powerpack and first development engine in calendar 2011. This paper will provide highlights of J-2X testing operations, engine test facilities, development hardware, and plans.

  10. Witnessing quantum discord in 2xN systems

    SciTech Connect

    Bylicka, Bogna; Chruscinski, Dariusz

    2010-06-15

    Bipartite states with vanishing quantum discord are necessarily separable and hence positive partial transpose (PPT). We show that 2xN states satisfy additional property: the positivity of their partial transposition is recognized with respect to the canonical factorization of the original density operator. We call such states strong PPT (SPPT). Therefore, we provide a natural witness for a quantum discord: if a 2xN state is not SPPT it must contain nonclassical correlations measured by quantum discord. It is an analog of the celebrated Peres-Horodecki criterion: if a state is not PPT it must be entangled.

  11. Maltodextrin and fat preference deficits in "taste-blind" P2X2/P2X3 knockout mice.

    PubMed

    Sclafani, Anthony; Ackroff, Karen

    2014-07-01

    Adenosine triphosphate is a critical neurotransmitter in the gustatory response to the 5 primary tastes in mice. Genetic deletion of the purinergic P2X2/P2X3 receptor greatly reduces the neural and behavioral response to prototypical primary taste stimuli. In this study, we examined the behavioral response of P2X double knockout mice to maltodextrin and fat stimuli, which appear to activate additional taste channels. P2X double knockout and wild-type mice were given 24-h choice tests (vs. water) with ascending concentrations of Polycose and Intralipid. In Experiment 1, naive double knockout mice, unlike wild-type mice, were indifferent to dilute (0.5-4%) Polycose solutions but preferred concentrated (8-32%) Polycose to water. In a retest, the Polycose-experienced double knockout mice, like wild-type mice, preferred all Polycose concentrations. In Experiment 2, naive double knockout mice, unlike wild-type mice, were indifferent to dilute (0.313-2.5%) Intralipid emulsions but preferred concentrated (5-20%) Intralipid to water. In a retest, the fat-experienced double knockout mice, like wild-type mice, strongly preferred 0.313-5% Intralipid to water. These results indicate that the inherent preferences of mice for maltodextrin and fat are dependent upon adenosine triphosphate taste cell signaling. With experience, however, P2X double knockout mice develop strong preferences for the nontaste flavor qualities of maltodextrin and fat conditioned by the postoral actions of these nutrients.

  12. Credit WCT. Original 2'" x 2'" color negative is housed ...

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

    Credit WCT. Original 2-'" x 2-'" color negative is housed in the JPL Photography Laboratory, Pasadena, California. View shows small autoclave demonstrated by JPL staff member Milton Clay (JPL negative no. JPL-10286AC, 27 January 1989). - Jet Propulsion Laboratory Edwards Facility, Liner Laboratory, Edwards Air Force Base, Boron, Kern County, CA

  13. The P2X7 Receptor-Interleukin-1 Liaison

    PubMed Central

    Giuliani, Anna Lisa; Sarti, Alba C.; Falzoni, Simonetta; Di Virgilio, Francesco

    2017-01-01

    Interleukin-1β (IL-1β) plays a central role in stimulation of innate immune system and inflammation and in several chronic inflammatory diseases. These include rare hereditary conditions, e.g., auto-inflammatory syndromes, as well as common pathologies, such as type II diabetes, gout and atherosclerosis. A better understanding of IL-1β synthesis and release is particularly relevant for the design of novel anti-inflammatory drugs. One of the molecules mainly involved in IL-1β maturation is the P2X7 receptor (P2X7R), an ATP-gated ion channel that chiefly acts through the recruitment of the NLRP3 inflammasome-caspase-1 complex. In this review, we will summarize evidence supporting the key role of the P2X7R in IL-1β production, with special emphasis on the mechanism of release, a process that is still a matter of controversy. Four different models have been proposed: (i) exocytosis via secretory lysosomes, (ii) microvesicles shedding from plasma membrane, (iii) release of exosomes, and (iv) passive efflux across a leaky plasma membrane during pyroptotic cell death. All these models involve the P2X7R. PMID:28360855

  14. Testing and Functions of the J2X Gas Generator

    NASA Technical Reports Server (NTRS)

    Miller, Nicholas

    2009-01-01

    The Ares I, NASA s new solid rocket based crew launch vehicle, is a two stage in line rocket that has made its waytothe forefront of NASA s endeavors. The Ares I s Upper Stage (US) will be propelled by a J-2X engine which is fueled by liquid hydrogen and liquid oxygen. The J-2X is a variation based on two of its predecessor s, the J-2 and J-2S engines. ET50 is providing the design support for hardware required to run tests on the J-2X Gas Generator (GG) that increases the delivery pressure of the supplied combustion fuels that the engine burns. The test area will be running a series of tests using different lengths and curved segments of pipe and different sized nozzles to determine the configuration that best satisfies the thrust, heat, and stability requirements for the engine. I have had to research the configurations that are being tested and gain an understanding of the purpose of the tests. I then had to research the parts that would be used in the test configurations. I was taken to see parts similar to the ones used in the test configurations and was allowed to review drawings and dimensions used for those parts. My job over this summer has been to use the knowledge I have gained to design, model, and create drawings for the un-fabricated parts that are necessary for the J-2X Workhorse Gas Generator Phase IIcTest.

  15. Credit WCT. Original 2'" x 2%" color negative is housed ...

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

    Credit WCT. Original 2-'" x 2-%" color negative is housed in the JPL Photography Laboratory, Pasadena, California. This view shows the propellant cutter as it was originally installed (JPL negative no. 381-2274A, 29 June 1962) - Jet Propulsion Laboratory Edwards Facility, Preparation Building, Edwards Air Force Base, Boron, Kern County, CA

  16. J-2X Powerpack Test Lights Up the Night

    NASA Video Gallery

    In a brief but dazzling display, a 1.86-second burst of flame emerges from the A-1 test stand at Stennis Space Center as NASA kicks off the first in a series of J-2X powerpack tests the evening of ...

  17. Quadrupole Order in the Frustrated Pyrochlore Tb2 +xTi2 -xO7 +y

    NASA Astrophysics Data System (ADS)

    Takatsu, H.; Onoda, S.; Kittaka, S.; Kasahara, A.; Kono, Y.; Sakakibara, T.; Kato, Y.; Fâk, B.; Ollivier, J.; Lynn, J. W.; Taniguchi, T.; Wakita, M.; Kadowaki, H.

    2016-05-01

    A hidden order that emerges in the frustrated pyrochlore Tb2 +xTi2 -xO7 +y with Tc=0.53 K is studied using specific heat, magnetization, and neutron scattering experiments on a high-quality single crystal. Semiquantitative analyses based on a pseudospin-1 /2 Hamiltonian for ionic non-Kramers magnetic doublets demonstrate that it is an ordered state of electric quadrupole moments. The elusive spin liquid state of the nominal Tb2 Ti2 O7 is most likely a U (1 ) quantum spin-liquid state.

  18. Effect of P2X4 and P2X7 receptor antagonism on the pressure diuresis relationship in rats

    PubMed Central

    Menzies, Robert I.; Unwin, Robert J.; Dash, Ranjan K.; Beard, Daniel A.; Cowley Jr., Allen W.; Carlson, Brian E.; Mullins, John J.; Bailey, Matthew A.

    2013-01-01

    Reduced glomerular filtration, hypertension and renal microvascular injury are hallmarks of chronic kidney disease, which has a global prevalence of ~10%. We have shown previously that the Fischer (F344) rat has lower GFR than the Lewis rat, and is more susceptible to renal injury induced by hypertension. In the early stages this injury is limited to the pre-glomerular vasculature. We hypothesized that poor renal hemodynamic function and vulnerability to vascular injury are causally linked and genetically determined. In the present study, normotensive F344 rats had a blunted pressure diuresis relationship, compared with Lewis rats. A kidney microarray was then interrogated using the Endeavour enrichment tool to rank candidate genes for impaired blood pressure control. Two novel candidate genes, P2rx7 and P2rx4, were identified, having a 7− and 3− fold increased expression in F344 rats. Immunohistochemistry localized P2X4 and P2X7 receptor expression to the endothelium of the pre-glomerular vasculature. Expression of both receptors was also found in the renal tubule; however there was no difference in expression profile between strains. Brilliant Blue G (BBG), a relatively selective P2X7 antagonist suitable for use in vivo, was administered to both rat strains. In Lewis rats, BBG had no effect on blood pressure, but increased renal vascular resistance, consistent with inhibition of some basal vasodilatory tone. In F344 rats BBG caused a significant reduction in blood pressure and a decrease in renal vascular resistance, suggesting that P2X7 receptor activation may enhance vasoconstrictor tone in this rat strain. BBG also reduced the pressure diuresis threshold in F344 rats, but did not alter its slope. These preliminary findings suggest a physiological and potential pathophysiological role for P2X7 in controlling renal and/or systemic vascular function, which could in turn affect susceptibility to hypertension-related kidney damage. PMID:24187541

  19. Functional properties of five Dictyostelium discoideum P2X receptors.

    PubMed

    Baines, Abigail; Parkinson, Katie; Sim, Joan A; Bragg, Laricia; Thompson, Christopher R L; North, R Alan

    2013-07-19

    The Dictyostelium discoideum genome encodes five proteins that share weak sequence similarity with vertebrate P2X receptors. Unlike vertebrate P2X receptors, these proteins are not expressed on the surface of cells, but populate the tubules and bladders of the contractile vacuole. In this study, we expressed humanized cDNAs of P2XA, P2XB, P2XC, P2XD, and P2XE in human embryonic kidney cells and altered the ionic and proton environment in an attempt to reflect the situation in amoeba. Recording of whole-cell membrane currents showed that four receptors operated as ATP-gated channels (P2XA, P2XB, P2XD, and P2XE). At P2XA receptors, ATP was the only effective agonist of 17 structurally related putative ligands that were tested. Extracellular sodium, compared with potassium, strongly inhibited ATP responses in P2XB, P2XD, and P2XE receptors. Increasing the proton concentration (pH 6.2) accelerated desensitization at P2XA receptors and decreased currents at P2XD receptors, but increased the currents at P2XB and P2XE receptors. Dictyostelium lacking P2XA receptors showed impaired regulatory volume decrease in hypotonic solution. This phenotype was readily rescued by overexpression of P2XA and P2XD receptors, partially rescued by P2XB and P2XE receptors, and not rescued by P2XC receptors. The failure of the nonfunctional receptor P2XC to restore the regulatory volume decrease highlights the importance of ATP activation of P2X receptors for a normal response to hypo-osmotic shock, and the weak rescue by P2XB and P2XE receptors indicates that there is limited functional redundancy among Dictyostelium P2X receptors.

  20. Activation and Regulation of Purinergic P2X Receptor Channels

    PubMed Central

    Coddou, Claudio; Yan, Zonghe; Obsil, Tomas; Huidobro-Toro, J. Pablo

    2011-01-01

    Mammalian ATP-gated nonselective cation channels (P2XRs) can be composed of seven possible subunits, denoted P2X1 to P2X7. Each subunit contains a large ectodomain, two transmembrane domains, and intracellular N and C termini. Functional P2XRs are organized as homomeric and heteromeric trimers. This review focuses on the binding sites involved in the activation (orthosteric) and regulation (allosteric) of P2XRs. The ectodomains contain three ATP binding sites, presumably located between neighboring subunits and formed by highly conserved residues. The detection and coordination of three ATP phosphate residues by positively charged amino acids are likely to play a dominant role in determining agonist potency, whereas an AsnPheArg motif may contribute to binding by coordinating the adenine ring. Nonconserved ectodomain histidines provide the binding sites for trace metals, divalent cations, and protons. The transmembrane domains account not only for the formation of the channel pore but also for the binding of ivermectin (a specific P2X4R allosteric regulator) and alcohols. The N- and C- domains provide the structures that determine the kinetics of receptor desensitization and/or pore dilation and are critical for the regulation of receptor functions by intracellular messengers, kinases, reactive oxygen species and mercury. The recent publication of the crystal structure of the zebrafish P2X4.1R in a closed state provides a major advance in the understanding of this family of receptor channels. We will discuss data obtained from numerous site-directed mutagenesis experiments accumulated during the last 15 years with reference to the crystal structure, allowing a structural interpretation of the molecular basis of orthosteric and allosteric ligand actions. PMID:21737531

  1. J-2X, The Engine of the Future

    NASA Technical Reports Server (NTRS)

    Smith, Gail

    2009-01-01

    My project was two-fold, with both parts involving the J-2X Upper Stage engine (which will be used on both the Ares I and V). Mainly, I am responsible for using a program called Iris to create visual represen tations of the rocket engine's telemetry data. Also, my project includes the application of my newly acquired Pro Engineer skills in develo ping a 3D model of the engine's nozzle.

  2. Engine Gimbal Requirements for Ground Testing of J-2X

    NASA Technical Reports Server (NTRS)

    Kovalcik, Julia; Leahy, Joe

    2009-01-01

    Based on the Apollo-era J-2 that powered the second and third stages of the Saturn V, the current J-2X is the liquid hydrogen and oxygen high-altitude rocket engine in development for both the Ares I Upper Stage and Ares V Earth Departure Stage. During my summer 2009 internship, J-2X was at a stage in its design maturity where verification testing needed to be considered for the benefit of adequate test facility preparation. My task was to focus on gimbal requirements and gimbal related hot-fire test plans. Facility capabilities were also of interest, specifically for hot-fire testing slated to occur at test stands A-1, A-2, and A-3 at Stennis Space Center(SSC) in Bay St. Louis, Mississippi. Gimbal requirements and stage interface conditions were investigated by applying a top-to-bottom systems engineering approach, which involved system level requirements, engine level requirements from both government and engine contractor perspectives, component level requirements, and the J-2X to Upper Stage and Earth Departure Stage interface control documents. Previous hydrogen and oxygen liquid rocket engine gimbal verification methods were researched for a glimpse at lessons learned. Discussion among the J-2X community affected by gimballing was organized to obtain input relative to proper verification of their respective component. Implementing suggestions such as gimbal pattern, angulated dwell time, altitude testing options, power level, and feed line orientation, I was able to match tests to test stands in the A Complex at SSC. Potential test capability gaps and risks were identified and pursued. The culmination of all these efforts was to coordinate with SSC to define additional facility requirements for both the A-3 altitude test stand that is currently under construction and the A-1 sea level test stand which is being renovated

  3. The J-2X Fuel Turbopump - Design, Development, and Test

    NASA Technical Reports Server (NTRS)

    Tellier, James G.; Hawkins, Lakiesha V.; Shinguchi, Brian H.; Marsh, Matthew W.

    2011-01-01

    Pratt and Whitney Rocketdyne (PWR), a NASA subcontractor, is executing the design, development, test, and evaluation (DDT&E) of a liquid oxygen, liquid hydrogen two hundred ninety four thousand pound thrust rocket engine initially intended for the Upper Stage (US) and Earth Departure Stage (EDS) of the Constellation Program Ares-I Crew Launch Vehicle (CLV). A key element of the design approach was to base the new J-2X engine on the heritage J-2S engine with the intent of uprating the engine and incorporating SSME and RS-68 lessons learned. The J-2S engine was a design upgrade of the flight proven J-2 configuration used to put American astronauts on the moon. The J-2S Fuel Turbopump (FTP) was the first Rocketdyne-designed liquid hydrogen centrifugal pump and provided many of the early lessons learned for the Space Shuttle Main Engine High Pressure Fuel Turbopumps. This paper will discuss the design trades and analyses performed for the current J-2X FTP to increase turbine life; increase structural margins, facilitate component fabrication; expedite turbopump assembly; and increase rotordynamic stability margins. Risk mitigation tests including inducer water tests, whirligig turbine blade tests, turbine air rig tests, and workhorse gas generator tests characterized operating environments, drove design modifications, or identified performance impact. Engineering design, fabrication, analysis, and assembly activities support FTP readiness for the first J-2X engine test scheduled for July 2011.

  4. P2X4R+ microglia drive neuropathic pain

    PubMed Central

    Beggs, Simon; Trang, Tuan; Salter, Michael W

    2016-01-01

    Neuropathic pain, the most debilitating of all clinical pain syndromes, may be a consequence of trauma, infection or pathology from diseases that affect peripheral nerves. Here we provide a framework for understanding the spinal mechanisms of neuropathic pain as distinct from those of acute pain or inflammatory pain. Recent work suggests that a specific microglia response phenotype characterized by de novo expression of the purinergic receptor P2X4 is critical for the pathogenesis of pain hypersensitivity caused by injury to peripheral nerves. Stimulating P2X4 receptors initiates a core pain signaling pathway mediated by release of brain-derived neurotrophic factor, which produces a disinhibitory increase in intracellular chloride in nociceptive (pain-transmitting) neurons in the spinal dorsal horn. The changes caused by signaling from P2X4R+ microglia to nociceptive transmission neurons may account for the main symptoms of neuropathic pain in humans, and they point to specific interventions to alleviate this debilitating condition. PMID:22837036

  5. J-2X Fuel Pump Impeller Seal Simulations

    NASA Technical Reports Server (NTRS)

    Schmauch, Preston B.; West, Jeffrey S.

    2011-01-01

    The J-2X engine was originally designed for the upper stage of the previously cancelled Crew Launch Vehicle. Although the Crew Launch Vehicle was cancelled the J-2X engine, which is currently undergoing hot-fire testing, may be used on future programs. The J-2X engine is a direct descendent of the J-2 engine which powered the upper stage during the Apollo program. Many changes including a thrust increase from 230K to 294K lbf have been implemented in this engine. The rotor-dynamic stability of the fuel turbopump is highly dependent on the tangential velocity of the fluid as it enters the the front face impeller seal. Rotor-dynamic analysis predicts that a much lower tangential velocity will be required for stability than was needed for previous engines. The geometry at the seal entrance for this engine is very complex and vastly different than previous engines. In order to better determine the fluid dynamics and tangential velocity in this seal several CFD simulations were performed. The results of these simulations show that for this seal geometry a great reduction in the tangential velocity is to be expected. The simulations also provided insight into methods that could be employed to drive the swirl velocity to near zero. Unsteady and time-averaged results of several simulations will be presented.

  6. A fluorescent approach for identifying P2X1 ligands

    PubMed Central

    Ruepp, Marc-David; Brozik, James A.; de Esch, Iwan J.P.; Farndale, Richard W.; Murrell-Lagnado, Ruth D.; Thompson, Andrew J.

    2015-01-01

    There are no commercially available, small, receptor-specific P2X1 ligands. There are several synthetic derivatives of the natural agonist ATP and some structurally-complex antagonists including compounds such as PPADS, NTP-ATP, suramin and its derivatives (e.g. NF279, NF449). NF449 is the most potent and selective ligand, but potencies of many others are not particularly high and they can also act at other P2X, P2Y and non-purinergic receptors. While there is clearly scope for further work on P2X1 receptor pharmacology, screening can be difficult owing to rapid receptor desensitisation. To reduce desensitisation substitutions can be made within the N-terminus of the P2X1 receptor, but these could also affect ligand properties. An alternative is the use of fluorescent voltage-sensitive dyes that respond to membrane potential changes resulting from channel opening. Here we utilised this approach in conjunction with fragment-based drug-discovery. Using a single concentration (300 μM) we identified 46 novel leads from a library of 1443 fragments (hit rate = 3.2%). These hits were independently validated by measuring concentration-dependence with the same voltage-sensitive dye, and by visualising the competition of hits with an Alexa-647-ATP fluorophore using confocal microscopy; confocal yielded kon (1.142 × 106 M−1 s−1) and koff (0.136 s−1) for Alexa-647-ATP (Kd = 119 nM). The identified hit fragments had promising structural diversity. In summary, the measurement of functional responses using voltage-sensitive dyes was flexible and cost-effective because labelled competitors were not needed, effects were independent of a specific binding site, and both agonist and antagonist actions were probed in a single assay. The method is widely applicable and could be applied to all P2X family members, as well as other voltage-gated and ligand-gated ion channels. This article is part of the Special Issue entitled ‘Fluorescent Tools in Neuropharmacology

  7. Robust optimization of 2x2 multimode interference couplers with fabrication uncertainties

    NASA Astrophysics Data System (ADS)

    Rehman, Samee ur; Langelaar, Matthijs; Van Keulen, Fred

    2013-03-01

    In this paper, we propose a novel design-for-manufacture strategy for integrated photonics which specifically addresses the commonly encountered scenario in which probability distributions of the manufacturing variations are not available, however their bounds are known. The best design point for the device, in the presence of these uncertainties, can be found by applying robust optimization. This is performed by minimizing the maximum realizable value of the objective with respect to the uncertainty set so that an optimum is found whose performance is relatively immune to fabrication variations. Instead of applying robust optimization directly on a computationally expensive simulation model of the integrated photonic device, we construct a cheap surrogate model by uniformly sampling the simulated device at different values of the design variables and interpolating the resulting objective using a Kriging metamodel. By applying robust optimization on the constructed surrogate, the global robust optimum can be found at low computational cost. As an illustration of the method's general applicability, we apply the robust optimization approach on a 2x2 multimode interference (MMI) coupler. We robustly minimize the imbalance in the presence of uncertainties arising from variations in the fabricated design geometry. For this example device, we also study the influence of the number of sample points on the quality of the metamodel and on the robust optimization process.

  8. Double P2X2/P2X3 Purinergic Receptor Knockout Mice Do Not Taste NaCl or the Artificial Sweetener SC45647

    PubMed Central

    Eddy, Meghan C.; Eschle, Benjamin K.; Barrows, Jennell; Hallock, Robert M.; Finger, Thomas E.

    2009-01-01

    The P2X ionotropic purinergic receptors, P2X2 and P2X3, are essential for transmission of taste information from taste buds to the gustatory nerves. Mice lacking both P2X2 and P2X3 purinergic receptors (P2X2/P2X3Dbl−/−) exhibit no taste-evoked activity in the chorda tympani and glossopharyngeal nerves when stimulated with taste stimuli from any of the 5 classical taste quality groups (salt, sweet, sour, bitter, and umami) nor do the mice show taste preferences for sweet or umami, or avoidance of bitter substances (Finger et al. 2005. ATP signaling is crucial for communication from taste buds to gustatory nerves. Science. 310[5753]:1495–1499). Here, we compare the ability of P2X2/P2X3Dbl−/− mice and P2X2/P2X3Dbl+/+ wild-type (WT) mice to detect NaCl in brief-access tests and conditioned aversion paradigms. Brief-access testing with NaCl revealed that whereas WT mice decrease licking at 300 mM and above, the P2X2/P2X3Dbl−/− mice do not show any change in lick rates. In conditioned aversion tests, P2X2/P2X3Dbl−/− mice did not develop a learned aversion to NaCl or the artificial sweetener SC45647, both of which are easily avoided by conditioned WT mice. The inability of P2X2/P2X3Dbl−/− mice to show avoidance of these taste stimuli was not due to an inability to learn the task because both WT and P2X2/P2X3Dbl−/− mice learned to avoid a combination of SC45647 and amyl acetate (an odor cue). These data suggest that P2X2/P2X3Dbl−/− mice are unable to respond to NaCl or SC45647 as taste stimuli, mirroring the lack of gustatory nerve responses to these substances. PMID:19833661

  9. The UC2-x - Carbon eutectic: A laser heating study

    NASA Astrophysics Data System (ADS)

    Manara, D.; Boboridis, K.; Morel, S.; De Bruycker, F.

    2015-11-01

    The UC2-x - carbon eutectic has been studied by laser heating and fast multi-wavelength pyrometry under inert atmosphere. The study has been carried out on three compositions, two of which close to the phase boundary of the UC2-x - C miscibility gap (with C/U atomic ratios 2 and 2.1), and one, more crucial, with a large excess of carbon (C/U = 2.82). The first two compositions were synthesised by arc-melting. This synthesis method could not be applied to the last composition, which was therefore completed directly by laser irradiation. The U - C - O composition of the samples was checked by using a combustion method in an ELTRA® analyser. The eutectic temperature, established to be 2737 K ± 20 K, was used as a radiance reference together with the cubic - tetragonal (α → β) solid state transition, fixed at 2050 K ± 20 K. The normal spectral emissivity of the carbon-richer compounds increases up to 0.7, whereas the value 0.53 was established for pure hypostoichiometric uranium dicarbide at the limit of the eutectic region. This increase is analysed in the light of the demixing of excess carbon, and used for the determination of the liquidus temperature (3220 K ± 50 K for UC2.82). Due to fast solid state diffusion, also fostered by the cubic - tetragonal transition, no obvious signs of a lamellar eutectic structure could be observed after quenching to room temperature. The eutectic surface C/UC2-x composition could be qualitatively, but consistently, followed during the cooling process with the help of the recorded radiance spectra. Whereas the external liquid surface is almost entirely constituted by uranium dicarbide, it gets rapidly enriched in demixed carbon upon freezing. Demixed carbon seems to quickly migrate towards the inner bulk during further cooling. At the α → β transition, uranium dicarbide covers again the almost entire external surface.

  10. Generators for the elliptic curve y2 = x3-nx

    NASA Astrophysics Data System (ADS)

    Fujita, Yasutsugu; Terai, Nobuhiro

    2010-07-01

    Let E:y2 = x3-nx be an elliptic curve over the rationals with a positive integer n. Mordell's theorem asserts that the group of rational points on E is finitely generated. Our interest is in the generators for its free part. Duquesne (2007) showed that if n = (2k2-2k+1)(18k2+30k+17) is square-free, then certain two points of infinite order can always be in a system of generators. We generalize this result and show that the same is true for "infinitely many" infinite families n = n(k,l) with two variables.

  11. The 2X-Hi disks of spiral galaxies

    NASA Astrophysics Data System (ADS)

    Koribalski, Bärbel S.

    2017-03-01

    The outskirts of galaxies - especially the very extended Hi disks of galaxies - are strongly affected by their local environment. I highlight the giant 2X-Hi disks of nearby galaxies (M 83, NGC 3621, and NGC 1512), studied as part of the Local Volume Hi Survey (LVHIS), their kinematics and relation to XUV disks, signatures of tidal interactions and accretion events, the M HI - D HI relation as well as the formation of tidal dwarf galaxies. - Using multi-wavelength data, I create 3D visualisations of the gas and stars in galaxies, with the shape of their warped disks obtained through kinematic modelling of their Hi velocity fields.

  12. Aqueous Rechargeable Alkaline CoxNi2-xS2/TiO2 Battery.

    PubMed

    Liu, Jilei; Wang, Jin; Ku, Zhiliang; Wang, Huanhuan; Chen, Shi; Zhang, Lili; Lin, Jianyi; Shen, Ze Xiang

    2016-01-26

    An electrochemical energy storage system with high energy density, stringent safety, and reliability is highly desirable for next-generation energy storage devices. Here an aqueous rechargeable alkaline CoxNi2-xS2 // TiO2 battery system is designed by integrating two reversible electrode processes associated with OH(-) insertion/extraction in the cathode part and Li ion insertion/extraction in the anode part, respectively. The prototype CoxNi2-xS2 // TiO2 battery is able to deliver high energy/power densities of 83.7 Wh/kg at 609 W/kg (based on the total mass of active materials) and good cycling stabilities (capacity retention 75.2% after 1000 charge/discharge cycles). A maximum volumetric energy density of 21 Wh/l (based on the whole packaged cell) has been achieved, which is comparable to that of a thin-film battery and better than that of typical commercial supercapacitors, benefiting from the unique battery and hierarchical electrode design. This hybrid system would enrich the existing aqueous rechargeable LIB chemistry and be a promising battery technology for large-scale energy storage.

  13. P2X receptors in cochlear Deiters' cells.

    PubMed

    Chen, C; Bobbin, R P

    1998-05-01

    1. The ionotropic purinoceptors in isolated Deiters' cells of guinea-pig cochlea were characterized by use of the whole-cell variant of the patch-clamp technique. 2. Extracellular application of adenosine 5'-triphosphate (ATP) induced a dose-dependent inward current when the cells were voltage-clamped at -80 mV. The ATP-induced current showed desensitization and had a reversal potential around -4 mV. 3. Increasing intracellular free Ca2+ by decreasing the concentration of EGTA in the pipette solution reduced the amplitude of the ATP-gated current. 4. The order of agonist potency was: 2-methylthioATP (2-meSATP)>ATP>benzoylbenzoyl-ATP (BzATP)>alpha,beta-methyleneATP (alpha,beta,meATP>adenosine 5'-diphosphate (ADP)>uridine 5'-triphosphate (UTP)>adenosine 5'-monophosphate (AMP)=adenosine (Ad). 5. Pretreatment with forskolin (10 microM), 8-bromoadenosine-3',5'-cyclophosphate (8-Br-cyclic AMP, 1 mM), 3-isobutyl-1-methylxanthine (IBMX, 1 mM) or phorbol-12-myristate-13-acetate (PMA, 1 microM) reversibly reduced the ATP-induced peak current. 6. The results are consistent with molecular biological data which indicate that P2X2 purinoceptors are present in Deiters' cells. In addition, the reduction of the ATP-gated current by activators of protein kinase A and protein kinase C indicates that these P2X2 purinoceptors can be functionally modulated by receptor phosphorylation.

  14. Powerpack Testing of the J2-X Oxidizer Turbopump

    NASA Technical Reports Server (NTRS)

    Jambusaria, Mitul; Szabo, Roland; Becht, David; Mulder, Andrew

    2013-01-01

    The J-2X PPA-2 (Powerpack 2) test series was conducted from February through December 2012 on the A1 test stand at NASA Stennis Space Center in a joint effort between Pratt and Whitney Rocketdyne (PWR) and NASA Marshall Space Flight Center (MSFC). The series consisted of 13 tests for a total hotfire duration close to 6500 seconds. Among the chief test objectives was characterization of the capabilities of the new J-2X turbopumps. This paper concentrates on the test results pertaining specifically to the Oxidizer Turbopump (OTP) operation in liquid oxygen (LOX). The two bladed inducer configuration that was tested had a 0.81% blade height tip clearance and incorporated the B-groove modification to the inducer tunnel outboard of the inducer leading edge. Data was collected on inducer suction performance, pump radial loading, and the pump dynamic environment in LOX. Comparisons were made to prior data collected on two geometrically similar subscale inducers tested in water at NASA MSFC (70% scale) and Concepts NREC (52% scale). In overview, the results of the powerpack testing were consistent with the radial load assessment from the water tests. The inducer performed differently in the other two categories, however. The inducer suction performance capability in LOX was notably improved. This was expected and is probably attributable to thermal suppression head (TSH) effects. While the dynamic environment was similar in most aspects to water test observations, the higher order cavitation (HOC) during the powerpack testing was much more benign.

  15. The J-2X Oxidizer Turbopump - Design, Development, and Test

    NASA Technical Reports Server (NTRS)

    Brozowski, Laura A.; Beatty, D. Preston; Shinguchi, Brian H.; Marsh, Matthew W.

    2011-01-01

    Pratt and Whitney Rocketdyne (PWR), a NASA subcontractor, is executing the Design, Development, Test, and Evaluation (DDT&E) of a liquid oxygen, liquid hydrogen two hundred ninety-four thousand pound thrust rocket engine initially intended for the Upper Stage (US) and Earth Departure Stage (EDS) of the Constellation Program Ares-I Crew Launch Vehicle (CLV). A key element of the design approach was to base the new J-2X engine on the heritage J-2S engine which was a design upgrade of the flight proven J-2 engine used to put American astronauts on the moon. This paper will discuss the design trades and analyses performed to achieve the required uprated Oxidizer Turbopump performance; structural margins and rotordynamic margins; incorporate updated materials and fabrication capability; and reflect lessons learned from legacy and existing Liquid Rocket Propulsion Engine turbomachinery. These engineering design, analysis, fabrication and assembly activities support the Oxidizer Turbopump readiness for J-2X engine test in 2011.

  16. 10 Years of Car-2-X Communication - a Success Story?

    NASA Astrophysics Data System (ADS)

    Wischhof, Lars; Ebner, André

    2012-05-01

    For more than ten years, car-2-x communication has been a major topic of research in the scientific community and an important development focus for the automotive industry. First, this article takes a retrospective look at the evolution of car-2-x and the two different communication paradigms: decentralized car-2-car communication and centralized cellular solutions. Afterwards, a comparison of their technical advantages and limitations is presented, respectively. The result shows that in order to implement safety-relevant applications, car-2-car communication has strong advantages compared to cellular technologies but requires high market penetration. However, its introduction solely for safety applications is difficult since the required penetration will not be achieved until several years after initial deployment. Therefore, car-2-car communication must provide a benefit to the customer, even in the phase of market introduction. For this purpose, the article outlines an approach called SODAD (Segment-Oriented Data Abstraction and Dissemination). It offers a possibility to introduce decentralized vehicular applications with early customer benefit, in order to enable safety applications based on car-2-car communication on a long term.

  17. Residual Chemosensory Capabilities in Double P2X2/P2X3 Purinergic Receptor Null Mice: Intraoral or Postingestive Detection?

    PubMed Central

    Hallock, Robert M.; Tatangelo, Marco; Barrows, Jennell

    2009-01-01

    Mice lacking the purinergic receptors, P2X2 and P2X3 (P2X2/P2X3Dbl−/−), exhibit essentially no tastant-evoked activity in the chorda tympani and glossopharyngeal nerves and substantial loss of tastant-evoked behavior as measured in long-term intake experiments. To assess whether the residual chemically driven behaviors in these P2X2/P2X3Dbl−/− mice were attributable to postingestive detection or oropharyngeal detection of the compounds, we used brief access lickometer tests to assess the behavioral capabilities of the P2X2/P2X3Dbl−/− animals. The P2X2/P2X3Dbl−/− mice showed avoidance to high levels (10 mM quinine and 10–30 mM denatonium benzoate) of classical “bitter”-tasting stimuli in 24-h, 2-bottle preference tests but minimal avoidance of these substances in the lickometer tests, suggesting that the strong avoidance in the intake tests was largely mediated by post-oral chemosensors. Similarly, increases in consumption of 1 M sucrose by P2X2/P2X3Dbl−/− mice in long-term intake tests were not mirrored by increases in consumption of sucrose in lickometer tests, suggesting that sucrose detection in these mice is mediated by postingestive consequences. In contrast, in brief access tests, P2X2/P2X3Dbl−/− mice avoided citric acid and hydrochloric acid at the same concentrations as their wild-type counterparts, indicating that these weak acids activate oropharyngeal chemoreceptors. PMID:19833662

  18. Development of a 2x2 optical switch for plastic optical fiber using liquid crystal cells

    NASA Astrophysics Data System (ADS)

    Vazquez, Carmen; Sanchez-Pena, J. M.; Contreras, Pedro; Pontes, M. A. J.

    2005-07-01

    A 2x2 optical switch for plastic optical fibre (POF) has been developed, able to work for both 660 and 850nm simultaneous and independently of the input light's polarization, improving previous developments. The device has four bidirectional optical ports, and is able to switch from each port to any other. In this way, there are three operation modes: straight (each input connected to the corresponding output), crossed (inputs and outputs crosses) and closed (inputs connected on the one part, and output connected on the other part). As the device is bidirectional, inputs and outputs are interchangeable. The switching process is carried out by a set of Polarized Beam Splitters, Liquid Crystal cells, λ/4 plates, lens and mirrors. An electronic circuitry has been developed to control the state of the optical switch, which is shown in a Liquid Crystal Display. The system has been tested for both 660nm and 850nm, and the optical switch exhibits miliseconds switching times, an optical interchannel crosstalk better than -25 dB, and low power consumption. Applications of the switch include systems where a redundant path is needed to guarantee communication, such as safety systems in automobiles, LANs, telemedicine, heavy machinery in the industry along with coarse WDM GI (graded index) POF networks. Device size reduction is under development.

  19. Cathode bubbles induced by moisture electrolysis in TiO2-x -based resistive switching cells

    NASA Astrophysics Data System (ADS)

    Yin, Qiaonan; Wei, Chunyang; Xia, Yidong; Xu, Bo; Yin, Jiang; Liu, Zhiguo

    2016-03-01

    H2 production has been predicted in some metal-insulator-metal resistive switching devices and similar structures, but experimentally has not yet been reported. Here we discovered cathode bubbles in Pt/TiO2-x /Pt unipolar resistive switching cells when electroforming is implemented in a humid environment. But then these bubbles are absent when cells are operated in an anhydrous environment. The focused ion beam technique was used to observe the deformation of the cell induced by bubbles. These bubbles are deduced to be filled with H2 generated at the cathode by the reduction of protons from adsorbed water. Reduced oxides containing abundant oxygen vacancies facilitate the dissociation of adsorbed water and supply sufficient protons diffusing towards the cathode.

  20. Ordering processes in monophase CeH2+x

    NASA Astrophysics Data System (ADS)

    Ratishvili, I. G.; Vajda, P.; Boukraa, A.; Namoradze, N. Z.

    1994-06-01

    The hydrogen ordering processes in the β phase of the rare-earth hydride system CeH2+x are analyzed. It is assumed that, within the discussed concentration range (x<0.75), the stable states of the metal-hydrogen system are homogeneous monophase solutions with fixed concentrations. The description of ordering is based upon the mean-field approximation of the static-concentration-waves theory. The relevant energy constants describing the H-H interactions are determined using available experimental data corresponding to the order-disorder transformation temperatures. It is shown that in the system under consideration there exists (in the concentration range x>=0.35), besides the usual order-disorder transformation, an additional order-order transition at low temperatures which, in some cases (for x>0.44), has a two-step character.

  1. Magnetic structure of NiS2 -xSex

    NASA Astrophysics Data System (ADS)

    Yano, S.; Louca, Despina; Yang, J.; Chatterjee, U.; Bugaris, D. E.; Chung, D. Y.; Peng, L.; Grayson, M.; Kanatzidis, Mercouri G.

    2016-01-01

    NiS2 -2 xSex is revisited to determine the magnetic structure using neutron diffraction and magnetic representational analysis. Upon cooling, the insulating parent compound, NiS2, becomes antiferromagnetic with two successive magnetic transitions. The first transition (M 1 ) occurs at TN˜39 K with Γ1ψ1 symmetry and a magnetic propagation vector of k =(000 ) . The second transition (M 2 ) occurs at TN˜30 K with k =(0.5 ,0.5 ,0.5 ) and a Γ1ψ2 symmetry with face-centered translations, giving rise to four possible magnetic domains. With doping, the system becomes metallic. The transition to the M 2 state is suppressed prior to x =0.4 while the M 1 state persists. The M 1 magnetic structure gradually vanishes by x ˜0.8 at a lower concentration than previously reported. The details of the magnetic structures are provided.

  2. Thermodynamics of fission products in UO2+-x

    SciTech Connect

    Nerikar, Pankaj V

    2009-01-01

    The stabilities of selected fission products - Xe, Cs, and Sr - are investigated as a function of non-stoichiometry x in UO{sub 2{+-}x}. In particular, density functional theory (OFT) is used to calculate the incorporation and solution energies of these fission products at the anion and cation vacancy sites, at the divacancy, and at the bound Schottky defect. In order to reproduce the correct insulating state of UO{sub 2}, the DFT calculations are performed using spin polarization and with the Hubbard U tenn. In general, higher charge defects are more soluble in the fuel matrix and the solubility of fission products increases as the hyperstoichiometry increases. The solubility of fission product oxides is also explored. CS{sub 2}O is observed as a second stable phase and SrO is found to be soluble in the UO{sub 2} matrix for all stoichiometries. These observations mirror experimentally observed phenomena.

  3. First-principles calculations of PuO(2+/-x).

    PubMed

    Petit, L; Svane, A; Szotek, Z; Temmerman, W M

    2003-07-25

    The electronic structure of PuO(2+/-x) was studied using first-principles quantum mechanics, realized with the self-interaction corrected local spin density method. In the stoichiometric PuO2 compound, Pu occurs in the Pu(IV) oxidation state, corresponding to a localized f4 shell. If oxygen is introduced onto the octahedral interstitial site, the nearby Pu atoms turn into Pu(V) (f3) by transferring electrons to the oxygen. Oxygen vacancies cause Pu(III) (f5) to form by taking up electrons released by oxygen. At T = 0, the PuO2 compound is stable with respect to free oxygen, but the delicate energy balance suggests the possible deterioration of the material during long-term storage.

  4. SU(2) x U(1) vacuum and the Centauro events

    NASA Technical Reports Server (NTRS)

    Kazanas, D.; Balasubrahmanyan, V. K.; Streitmatter, R. E.

    1985-01-01

    It is proposed that the fireballs invoked to explain the Centauro events are bubbles of a metastable superdense state of nuclear matter, created in high energy (E approximately 10 to the 15th power eV) cosmic ray collisions at the top of the atmosphere. If these bubbles are created with a Lorentz factor gamma approximately equals 10 at their CM frame, the objections against the origin of these events in cosmic ray interactions are overcome. A relationship then between their lifetime, tau, and the threshold energy for bubble formation, E sub th, appears to be insensitive to the value of tau and always close to E sub th approximately 10 to 15th power eV. Finally it is speculated that these bubbles might be manifestations of the SU(2) x U(1) false vacuum excited in these collisions. The absence of in the Centauro events is then explained by the decay modes of these excitations.

  5. P2X receptors in cochlear Deiters' cells

    PubMed Central

    Chen, Chu; Bobbin, Richard P

    1998-01-01

    The ionotropic purinoceptors in isolated Deiters' cells of guinea-pig cochlea were characterized by use of the whole-cell variant of the patch-clamp technique.Extracellular application of adenosine 5′-triphosphate (ATP) induced a dose-dependent inward current when the cells were voltage-clamped at −80 mV. The ATP-induced current showed desensitization and had a reversal potential around −4 mV.Increasing intracellular free Ca2+ by decreasing the concentration of EGTA in the pipette solution reduced the amplitude of the ATP-gated current.The order of agonist potency was: 2-methylthioATP (2-meSATP)>ATP>benzoylbenzoyl-ATP (BzATP)>α,β-methyleneATP (α,β,meATP>adenosine 5′-diphosphate (ADP)>uridine 5′-triphosphate (UTP)>adenosine 5′-monophosphate (AMP)=adenosine (Ad).Pretreatment with forskolin (10 μM), 8-bromoadenosine-3′,5′-cyclophosphate (8-Br-cyclic AMP, 1 mM), 3-isobutyl-1-methylxanthine (IBMX, 1 mM) or phorbol-12-myristate-13-acetate (PMA, 1 μM) reversibly reduced the ATP-induced peak current.The results are consistent with molecular biological data which indicate that P2X2 purinoceptors are present in Deiters' cells. In addition, the reduction of the ATP-gated current by activators of protein kinase A and protein kinase C indicates that these P2X2 purinoceptors can be functionally modulated by receptor phosphorylation. PMID:9641551

  6. Subscale Injector Testing to Support J-2X Engine Development

    NASA Technical Reports Server (NTRS)

    Protz, Christopher; Elam, Sandy; Weber, Jim; Miller, Ken

    2008-01-01

    The J-2X engine being pursued for the Ares I will be a derivative of the J-2 engine developed by Pratt & Whitney Rocketdyne (PWR). As part of the engine development, a subscale injector was fabricated by PWR and hot-fire tested at NASA s Marshall Space Flight Center (MSFC) to evaluate performance data. This subscale injector had a reduced injector diameter and fewer elements than the full scale design, but the element density (#elements / injector area), and element geometries nearly identical to the full scale design. Three different materials were used for the LOX posts in order to test for durability. The subscale injector included 46 standard elements and 6 baffle elements, corresponding to the ratio of baffled elements to core elements in the full scale design. The baffle elements were included to demonstrate thermal compatibility of the baffles and to more closely represent the full scale performance. Fifteen hot-fire tests were conducted totaling over 200 seconds of mainstage time on the injector. Chamber pressures with oxygen/hydrogen propellants ranged from 870-1380 psig with mixture ratios ranging from 4.8-6.1. Fuel manifold inlet temperatures were varied from 190 to 300 R. Modular, water cooled, calorimeter chamber assemblies were used to provide heating rate data and evaluate the effects of characteristic length (L*). Performance was evaluated relative to the resulting characteristic velocity (C*) efficiency. Performance met the value required in order to proceed with this design for the full scale hardware. Hardware inspections show no evidence of cracking at the tip of the LOX post for any of the materials tested. Minor erosion of the baffle element tips was observed in the early testing. A design change was quickly implemented and tested, and this change resolved the issue. Development of the J-2X is continuing with this element density and design.

  7. Combustion Stability Analyses for J-2X Gas Generator Development

    NASA Technical Reports Server (NTRS)

    Hulka, J. R.; Protz, C. S.; Casiano, M. J.; Kenny, R. J.

    2010-01-01

    The National Aeronautics and Space Administration (NASA) is developing a liquid oxygen/liquid hydrogen rocket engine for upper stage and trans-lunar applications of the Ares vehicles for the Constellation program. This engine, designated the J-2X, is a higher pressure, higher thrust variant of the Apollo-era J-2 engine. Development was contracted to Pratt & Whitney Rocketdyne in 2006. Over the past several years, development of the gas generator for the J-2X engine has progressed through a variety of workhorse injector, chamber, and feed system configurations. Several of these configurations have resulted in injection-coupled combustion instability of the gas generator assembly at the first longitudinal mode of the combustion chamber. In this paper, the longitudinal mode combustion instabilities observed on the workhorse test stand are discussed in detail. Aspects of this combustion instability have been modeled at the NASA Marshall Space Flight Center with several codes, including the Rocket Combustor Interaction Design and Analysis (ROCCID) code and a new lumped-parameter MatLab model. To accurately predict the instability characteristics of all the chamber and injector geometries and test conditions, several features of the submodels in the ROCCID suite of calculations required modification. Finite-element analyses were conducted of several complicated combustion chamber geometries to determine how to model and anchor the chamber response in ROCCID. A large suite of sensitivity calculations were conducted to determine how to model and anchor the injector response in ROCCID. These modifications and their ramification for future stability analyses of this type are discussed in detail. The lumped-parameter MatLab model of the gas generator assembly was created as an alternative calculation to the ROCCID methodology. This paper also describes this model and the stability calculations.

  8. Flexible subunit stoichiometry of functional human P2X2/3 heteromeric receptors.

    PubMed

    Kowalski, Maria; Hausmann, Ralf; Schmid, Julia; Dopychai, Anke; Stephan, Gabriele; Tang, Yong; Schmalzing, Günther; Illes, Peter; Rubini, Patrizia

    2015-12-01

    The aim of the present work was to clarify whether heterotrimeric P2X2/3 receptors have a fixed subunit stoichiometry consisting of one P2X2 and two P2X3 subunits as previously suggested, or a flexible stoichiometry containing also the inverse subunit composition. For this purpose we transfected HEK293 cells with P2X2 and P2X3 encoding cDNA at the ratios of 1:2 and 4:1, and analysed the biophysical and pharmacological properties of the generated receptors by means of the whole-cell patch-clamp technique. The concentration-response curves for the selective agonist α,β-meATP did not differ from each other under the two transfection ratios. However, co-expression of an inactive P2X2 mutant and the wild type P2X3 subunit and vice versa resulted in characteristic distortions of the α,β-meATP concentration-response relationships, depending on which subunit was expressed in excess, suggesting that HEK293 cells express mixtures of (P2X2)1/(P2X3)2 and (P2X2)2/(P2X3)1 receptors. Whereas the allosteric modulators H+ and Zn2+ failed to discriminate between the two possible heterotrimeric receptor variants, the α,β-meATP-induced responses were blocked more potently by the competitive antagonist A317491, when the P2X2 subunit was expressed in deficit of the P2X3 subunit. Furthermore, blue-native PAGE analysis of P2X2 and P2X3 subunits co-expressed in Xenopus laevis oocytes and HEK293 cells revealed that plasma membrane-bound P2X2/3 receptors appeared in two clearly distinct heterotrimeric complexes: a (P2X2-GFP)2/(P2X3)1 complex and a (P2X2-GFP)1/(P2X3)2 complex. These data strongly indicate that the stoichiometry of the heteromeric P2X2/3 receptor is not fixed, but determined in a permutational manner by the relative availability of P2X2 and P2X3 subunits.

  9. Mobility Patterns Informing V2X Research Projects: Eco-Routing and Electrified Roadway Project Examples

    SciTech Connect

    Gonder, Jeff; Brooker, Aaron; Burton, Evan; Wang, Lijuan; Wood, Eric

    2016-05-19

    Presentation given at an 'Expert Workshop on V2X Enabled Electric Vehicles' hosted at NREL on behalf of the International Energy Agency (IEA) Hybrid and Electric Vehicle Implementing Agreement for Task 28: Home Grids and V2X Technologies.

  10. Epitaxial growth and properties of MoOx(2<x <2.75) films

    NASA Astrophysics Data System (ADS)

    Bhosle, V.; Tiwari, A.; Narayan, J.

    2005-04-01

    We report the growth of epitaxial molybdenum oxide (MoOx,2<x<2.75) films on c plane of sapphire substrate using pulsed laser deposition in oxygen environment. The structure was characterized using x-ray diffraction, high resolution transmission electron microscopy and x-ray photoelectron spectroscopy (XPS). Electrical resistivity and optical properties were investigated using four-point-probe resistivity measurements and spectroscopy techniques, respectively. It was found that the film had a monoclinic structure based on MoO2 phase and showed an unusual combination of high conductivity and high transmittance in the visible region after annealing. The unusual combination of these properties was realized by systematically controlling the relative fraction of different oxidation states of molybdenum, namely Mo4+, Mo5+, and Mo6+ in the monoclinic phase. For a film 60nm thick and annealed at 250°C for 1h, the ratio of Mo6+/(Mo4++Mo5+) was determined to be ˜2.9/1 using XPS, and a typical value of transmittance was ˜65% and resistivity close to 1×10-3Ωcm. These results demonstrate growth of epitaxial MoOx films with tunable electrical and optical properties. Further optimization of these properties is expected to result in applications related to display panels, solar cells, chromogenic (photochromic, electrochromic, gasochromic) devices, and transparent conducting oxides. Our ability to grow epitaxial MoOx films can further aid their integration with optoelectronic and photonic devices.

  11. SU(2) x U(1) vacuum and the Centauro events

    NASA Technical Reports Server (NTRS)

    Kazanas, D.; Balasubrahmanyan, V. K.; Streitmatter, R. E.

    1984-01-01

    It is proposed that the fireballs invoked to explain the Centauro events are bubbles of a metastable superdense state of nuclear matter, created in high energy (E is approximately 10 to the 15th power eV) cosmic ray collisions at the top of the atmosphere. If these bubbles are created with a Lorentz factor gamma approximately = 10 at their CM frame, the objections against the origin of these events in cosmic ray interactions are overcome. Assuming further, that the Centauro events are to the explosive decay of these metastable bubbles, a relationship between their lifetime, tau, and the threshold energy for bubble formation, E sub th, is derived. The minimum lifetime consistent with such an interpretation in tau is approximately 10 to the -8th power sec, while the E sub th appears to be insensitive to the value of tau and always close to E sub th is approximately 10 to the 15th power eV. Finally it is speculated that if the available CM energy is thermalized in such collisions, these bubbles might be manifestations of excitations of the SU(2) x U(1) false vacuum. The absence of neutral pions in the Centauro events is then explained by the decay of these excitations.

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

    PubMed Central

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

    2015-01-01

    Several types of sex chromosome systems have been recorded among Gymnotiformes, including male and female heterogamety, simple and multiple sex chromosomes, and different mechanisms of origin and evolution. The X1X1X2X2/X1X2Y systems identified in three species of this order are considered homoplasic for the group. In the genus Brachyhypopomus, only B. gauderio presented this type of system. Herein we describe the karyotypes of Brachyhypopomus pinnicaudatus and B. n. sp. FLAV, which have an X1X1X2X2/X1X2Y sex chromosome system that evolved via fusion between an autosome and the Y chromosome. The morphology of the chromosomes and the meiotic pairing suggest that the sex chromosomes of B. gauderio and B. pinnicaudatus have a common origin, whereas in B . n. sp. FLAV the sex chromosome system evolved independently. However, we cannot discard the possibility of common origin followed by distinct processes of differentiation. The identification of two new karyotypes with an X1X1X2X2/X1X2Y sex chromosome system in Gymnotiformes makes it the most common among the karyotyped species of the group. Comparisons of these karyotypes and the evolutionary history of the taxa indicate independent origins for their sex chromosomes systems. The recurrent emergence of the X1X1X2X2/X1X2Y system may represent sex chromosomes turnover events in Gymnotiformes. PMID:26273225

  13. Ionotropic P2X ATP Receptor Channels Mediate Purinergic Signaling in Mouse Odontoblasts

    PubMed Central

    Shiozaki, Yuta; Sato, Masaki; Kimura, Maki; Sato, Toru; Tazaki, Masakazu; Shibukawa, Yoshiyuki

    2017-01-01

    ATP modulates various functions in the dental pulp cells, such as intercellular communication and neurotransmission between odontoblasts and neurons, proliferation of dental pulp cells, and odontoblast differentiation. However, functional expression patterns and their biophysical properties of ionotropic ATP (P2X) receptors (P2X1–P2X7) in odontoblasts were still unclear. We examined these properties of P2X receptors in mouse odontoblasts by patch-clamp recordings. K+-ATP, nonselective P2X receptor agonist, induced inward currents in odontoblasts in a concentration-dependent manner. K+-ATP-induced currents were inhibited by P2X4 and P2X7 selective inhibitors (5-BDBD and KN62, respectively), while P2X1 and P2X3 inhibitors had no effects. P2X7 selective agonist (BzATP) induced inward currents dose-dependently. We could not observe P2X1, 2/3, 3 selective agonist (αβ-MeATP) induced currents. Amplitudes of K+-ATP-induced current were increased in solution without extracellular Ca2+, but decreased in Na+-free extracellular solution. In the absence of both of extracellular Na+ and Ca2+, K+-ATP-induced currents were completely abolished. K+-ATP-induced Na+ currents were inhibited by P2X7 inhibitor, while the Ca2+ currents were sensitive to P2X4 inhibitor. These results indicated that odontoblasts functionally expressed P2X4 and P2X7 receptors, which might play an important role in detecting extracellular ATP following local dental pulp injury. PMID:28163685

  14. Synthesis and magnetic properties of single-crystalline Na2-xMn8O16 nanorods

    PubMed Central

    2011-01-01

    The synthesis of single-crystalline hollandite-type manganese oxides Na2-xMn8O16 nanorods by a simple molten salt method is reported for the first time. The nanorods were characterized by powder X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and a superconducting quantum interference device magnetometer. The magnetic measurements indicated that the nanorods showed spin glass behavior and exchange bias effect at low temperatures. The low-temperature magnetic behaviors can be explained by the uncompensated spins on the surface of the nanorods. PMID:21711626

  15. Polymorphism in 2-X-adamantane derivatives (X = Cl, Br).

    PubMed

    Negrier, Philippe; Barrio, María; Tamarit, Josep Ll; Mondieig, Denise

    2014-08-14

    The polymorphism of two 2-X-adamantane derivatives, X = Cl, X = Br, has been studied by X-ray powder diffraction and normal- and high-pressure (up to 300 MPa) differential scanning calorimetry. 2-Br-adamantane displays a low-temperature orthorhombic phase (space group P212121, Z = 4) and a high-temperature plastic phase (Fm3̅m, Z = 4) from 277.9 ± 1.0 K to the melting point at 413.4 ± 1.0 K. 2-Cl-adamantane presents a richer polymorphic behavior through the temperature range studied. At low temperature it displays a triclinic phase (P1̅, Z = 2), which transforms to a monoclinic phase (C2/c, Z = 8) at 224.4 ± 1.0 K, both phases being ordered. Two high-temperature orientationally disordered are found for this compound, one hexagonal (P63/mcm, Z = 6) at ca. 241 K and the highest one, cubic (Fm3̅m, Z = 4), being stable from 244 ± 1.0 K up to the melting point at 467.5 ± 1.0 K. No additional phase appears due to the increase in pressure within the studied range. The intermolecular interactions are found to be weak, especially for the 2-Br-adamantane compound for which the Br···Br as well as C-Br···H distances are larger than the addition of the van der Waals radii, thus confirming the availability of this compound for building up diamondoid blocks.

  16. P2X receptors in the cardiovascular system and their potential as therapeutic targets in disease.

    PubMed

    Ralevic, Vera

    2015-01-01

    This review considers the expression and roles of P2X receptors in the cardiovascular system in health and disease and their potential as therapeutic targets. P2X receptors are ligand gated ion channels which are activated by the endogenous ligand ATP. They are formed from the assembly of three P2X subunit proteins from the complement of seven (P2X1-7), which can associate to form homomeric or heteromeric P2X receptors. The P2X1 receptor is widely expressed in the cardiovascular system, being located in the heart, in the smooth muscle of the majority of blood vessels and in platelets. P2X1 receptors expressed in blood vessels can be activated by ATP coreleased with noradrenaline as a sympathetic neurotransmitter, leading to smooth muscle depolarisation and contraction. There is evidence that the purinergic component of sympathetic neurotransmission is increased in hypertension, identifying P2X1 receptors as a possible therapeutic target in this disorder. P2X3 and P2X2/3 receptors are expressed on cardiac sympathetic neurones and may, through positive feedback of neuronal ATP at this prejunctional site, amplify sympathetic neurotransmission. Activation of P2X receptors expressed in the heart increases cardiac myocyte contractility, and an important role of the P2X4 receptor in this has been identified. Deletion of P2X4 receptors in the heart depresses contractile performance in models of heart failure, while overexpression of P2X4 receptors has been shown to be cardioprotective, thus P2X4 receptors may be therapeutic targets in the treatment of heart disease. P2X receptors have been identified on endothelial cells. Although immunoreactivity for all P2X1-7 receptor proteins has been shown on the endothelium, relatively little is known about their function, with the exception of the endothelial P2X4 receptor, which has been shown to mediate endothelium-dependent vasodilatation to ATP released during shear stress. The potential of P2X receptors as therapeutic targets

  17. Expression, assembly and function of novel C-terminal truncated variants of the mouse P2X7 receptor: re-evaluation of P2X7 knockouts

    PubMed Central

    Masin, Marianela; Young, Christopher; Lim, KoiNi; Barnes, Sara J; Xu, Xing Jian; Marschall, Viola; Brutkowski, Wojciech; Mooney, Elizabeth R; Gorecki, Dariusz C; Murrell-Lagnado, Ruth

    2012-01-01

    BACKGROUND AND PURPOSE Splice variants of P2X7 receptor transcripts contribute to the diversity of receptor-mediated responses. Here, we investigated expression and function of C-terminal truncated (ΔC) variants of the mP2X7 receptor, which are predicted to escape inactivation in one strain of P2X7−/− mice (Pfizer KO). EXPERIMENTAL APPROACH Expression in wild-type (WT) and Pfizer KO tissue was investigated by reverse transcription (RT)-PCR and Western blot analysis. ΔC variants were also cloned and expressed in HEK293 cells to investigate their assembly, trafficking and function. KEY RESULTS RT-PCR indicates expression of a ΔC splice variant in brain, salivary gland (SG) and spleen from WT and Pfizer KO mice. An additional ΔC hybrid transcript, containing sequences of P2X7 upstream of exon 12, part of exon 13 followed in-frame by the sequence of the vector used to disrupt the P2X7 gene, was also identified in the KO mice. By blue native (BN) PAGE analysis and the use of cross linking reagents followed by SDS-PAGE, P2X7 trimers, dimers and monomers were detected in the spleen and SG of Pfizer KO mice. The molecular mass was reduced compared with P2X7 in WT mice tissue, consistent with a ΔC variant. When expressed in HEK293 cells the ΔC variants were inefficiently trafficked to the cell surface and agonist-evoked whole cell currents were small. Co-expressed with P2X7A, the ΔC splice variant acted in a dominant negative fashion to inhibit function. CONCLUSIONS AND IMPLICATIONS Pfizer KO mice are not null for P2X7 receptor expression but express ΔC variants with reduced function. PMID:21838754

  18. Z2 x Z3 Symmetry of Multferroic Vortices

    NASA Astrophysics Data System (ADS)

    Cheong, Sang-Wook

    2014-03-01

    Hexagonal REMnO3 (RE = rare earths) with RE =Ho-Lu, Y, and Sc, is an improper ferroelectric where the size mismatch between RE and Mn induces a trimerization-type structural phase transition, and this structural transition leads to three structural domains, each of which can support two directions of ferroelectric polarization. We reported that domains in h-REMnO3 meet in cloverleaf arrangements that cycle through all six domain configurations, Occurring in pairs, the cloverleafs can be viewed as vortices and antivortices, in which the cycle of domain configurations is reversed. Vortices and antivortices are topological defects: even in a strong electric field they won't annihilate. These ferroelectric vortices/antivortices are found to be associated with intriguing collective magnetism at domain walls, reflecting the multiferroic nature of vortices. We have found that an intriguing, but seemingly irregular network of a zoo of multiferroic vortices and antivortices in h-REMnO3 can be neatly analyzed in terms of graph theory, and this graph theoretical analysis reveals the emergence of Z2 × Z3 symmetry in the vortices/antivortices network. In addition, poling or self-poling due to a surface charge boundary condition induces global topological condensation of the network through breaking of the Z2 part of the Z2 × Z3 symmetry. The opposite process of restoring the Z2 symmetry can be considered as topological evaporation. It turns out that these Z2xZ3 vortices are, in fact, three-dimensional vortex loops, which result from the emergent continuous U(1) symmetry near the critical temperature. This spontaneous trapping of topological defects in the process of undergoing a continuous phase transition is important to understand numerous novel phenomena such as the early stage of universe after big bang. The so-called Kibble-Zurek mechanism was proposed for the trapping process of topological defects right after big bang. It appears that the Kibble-Zurek mechanism is also

  19. A scaled quantum mechanical force field for the sulfuryl halides. I. The symmetric halides SO2X2 (X=F, Cl, Br).

    PubMed

    Fernández, L E; Verón, M G; Varetti, E L

    2004-01-01

    Force fields and vibrational wavenumbers were calculated for the molecules SO2X2 (X=F, Cl, Br) using DFT techniques. The previously available experimental data and assignments for SO2F2 and SO2Cl2 were compared with the theoretical results and revised, and new low temperature infrared and Raman data were obtained for SO2Cl2. These data were subsequently used in the definition of scaled quantum mechanics force fields for such molecules. Adjusted wavenumbers were also predicted for the still unknown SO2Br2. A comparison is made with results published for the VO2X2- anions.

  20. A scaled quantum mechanical force field for the sulfuryl halides. I. The symmetric halides SO 2X 2 (X=F, Cl, Br)

    NASA Astrophysics Data System (ADS)

    Fernández, L. E.; Verón, M. G.; Varetti, E. L.

    2004-01-01

    Force fields and vibrational wavenumbers were calculated for the molecules SO 2X 2 (X=F, Cl, Br) using DFT techniques. The previously available experimental data and assignments for SO 2F 2 and SO 2Cl 2 were compared with the theoretical results and revised, and new low temperature infrared and Raman data were obtained for SO 2Cl 2. These data were subsequently used in the definition of scaled quantum mechanics force fields for such molecules. Adjusted wavenumbers were also predicted for the still unknown SO 2Br 2. A comparison is made with results published for the VO 2X 2- anions.

  1. Self-Rectifying Resistive Switching Memory with Ultralow Switching Current in Pt/Ta2O5/HfO2- x /Hf Stack

    NASA Astrophysics Data System (ADS)

    Ma, Haili; Feng, Jie; Lv, Hangbing; Gao, Tian; Xu, Xiaoxin; Luo, Qing; Gong, Tiancheng; Yuan, Peng

    2017-02-01

    In this study, we present a bilayer resistive switching memory device with Pt/Ta2O5/HfO2- x /Hf structure, which shows sub-1 μA ultralow operating current, median switching voltage, adequate ON/OFF ratio, and simultaneously containing excellent self-rectifying characteristics. The control sample with single HfO2- x structure shows bidirectional memory switching properties with symmetrical I-V curve in low resistance state. After introducing a 28-nm-thick Ta2O5 layer on HfO2- x layer, self-rectifying phenomena appeared, with a maximum self-rectifying ratio (RR) of 4 × 103 observed at ±0.5 V. Apart from being a series resistance for the cell, the Ta2O5 rectifying layer also served as an oxygen reservoir which remains intact during the whole switching cycle.

  2. Molecular and functional characterization of human P2X(2) receptors.

    PubMed

    Lynch, K J; Touma, E; Niforatos, W; Kage, K L; Burgard, E C; van Biesen, T; Kowaluk, E A; Jarvis, M F

    1999-12-01

    P2X receptors are a family of ATP-gated ion channels. Four cDNAs with a high degree of homology to the rat P2X(2) receptor were isolated from human pituitary and pancreas RNA. Genomic sequence indicated that these cDNAs represent alternatively spliced messages. Northern analysis revealed high levels of human P2X(2) (hP2X(2)) message in the pancreas, and splice variants could be detected in a variety of tissues. Two cDNAs encoded functional ion channels when expressed in Xenopus oocytes, a receptor structurally homologous to the prototype rat P2X(2) receptor (called hP2X(2a)) and a variant containing a deletion within its cytoplasmic C terminus (called hP2X(2b)). Pharmacologically, these functional human P2X(2) receptors were virtually indistinguishable, with the P2X receptor agonists ATP, 2-methylthio-ATP, 2' and 3'-O-(4-benzoylbenzoyl)-ATP, and ATP5'-O-(3-thiotriphosphate) being approximately equipotent (EC(50) = 1 microM) in eliciting extracellular Ca(2+) influx. The P2 receptor agonists alpha,beta-methylene ATP, adenosine, adenosine 5'-O-(2-thiodiphosphate), and UTP were inactive at concentrations up to 100 microM. Both hP2X(2a) and hP2X(2b) receptors were sensitive to the P2 receptor antagonist pyridoxal-5-phosphate-6-azophenyl-2', 4'-disulfonic acid (IC(50) = 3 microM). In contrast to the analogous rat P2X(2) and P2X(2b) receptors, the desensitization rates of the hP2X(2a) and hP2X(2b) receptors were equivalent. Both functional forms of the human P2X(2) receptors formed heteromeric channels with the human P2X(3) receptor. These data demonstrate that the gene structure and mRNA heterogeneity of the P2X(2) receptor subtype are evolutionarily conserved between rat and human, but also suggest that alternative splicing serves a function other than regulating the desensitization rate of the human receptor.

  3. Macrophage activation and polarization modify P2X7 receptor secretome influencing the inflammatory process

    PubMed Central

    de Torre-Minguela, Carlos; Barberà-Cremades, Maria; Gómez, Ana I.; Martín-Sánchez, Fátima; Pelegrín, Pablo

    2016-01-01

    The activation of P2X7 receptor (P2X7R) on M1 polarized macrophages induces the assembly of the NLRP3 inflammasome leading to the release of pro-inflammatory cytokines and the establishment of the inflammatory response. However, P2X7R signaling to the NLRP3 inflammasome is uncoupled on M2 macrophages without changes on receptor activation. In this study, we analyzed P2X7R secretome in wild-type and P2X7R-deficient macrophages polarized either to M1 or M2 and proved that proteins released after P2X7R stimulation goes beyond caspase-1 secretome. The characterization of P2X7R-secretome reveals a new function of this receptor through a fine-tuning of protein release. We found that P2X7R stimulation in macrophages is able to release potent anti-inflammatory proteins, such as Annexin A1, independently of their polarization state suggesting for first time a potential role for P2X7R during resolution of the inflammation and not linked to the release of pro-inflammatory cytokines. These results are of prime importance for the development of therapeutics targeting P2X7R. PMID:26935289

  4. Tunable Dirac cone in the topological insulator Bi(2-x)Sb(x)Te(3-y)Se(y).

    PubMed

    Arakane, T; Sato, T; Souma, S; Kosaka, K; Nakayama, K; Komatsu, M; Takahashi, T; Ren, Zhi; Segawa, Kouji; Ando, Yoichi

    2012-01-24

    The three-dimensional topological insulator is a quantum state of matter characterized by an insulating bulk state and gapless Dirac cone surface states. Device applications of topological insulators require a highly insulating bulk and tunable Dirac carriers, which has so far been difficult to achieve. Here we demonstrate that Bi(2-x)Sb(x)Te(3-y)Se(y) is a system that simultaneously satisfies both of these requirements. For a series of compositions presenting bulk-insulating transport behaviour, angle-resolved photoemission spectroscopy reveals that the chemical potential is always located in the bulk band gap, whereas the Dirac cone dispersion changes systematically so that the Dirac point moves up in energy with increasing x, leading to a sign change of the Dirac carriers at x~0.9. Such a tunable Dirac cone opens a promising pathway to the development of novel devices based on topological insulators.

  5. Pharmacological identification of P2X1, P2X4 and P2X7 nucleotide receptors in the smooth muscles of human umbilical cord and chorionic blood vessels.

    PubMed

    Valdecantos, P; Briones, R; Moya, P; Germain, A; Huidobro-Toro, J P

    2003-01-01

    To ascertain the role of extracellular adenosine 5'-triphosphate (ATP) receptors in human placenta circulation, we identified and pharmacologically characterized the P2X receptor population in its superficial vessels. Total RNA was extracted from segments of chorionic and umbilical arteries and veins of terminal placentae delivered by vaginal or Caesarian births. Polymerase chain reaction (PCR), followed by sequencing of the products, identified the presence of P2X 1, 4, 5, 6, and 7mRNAs in smooth muscle from chorionic and umbilical arteries and veins. Umbilical vessels proximal to the fetus expressed the same population of P2X subtypes, except for the P2X(5), but additionally expressed the P2X(2). Rings of chorionic vessels contracted upon addition of nucleotides and analogs with the following relative rank order of potencies in arteries and veins: alpha,beta-methyleneATP>beta,gamma-methyleneATP>PNP>ATP=diBzATP>2-MeSATP>ADP>AMP; in umbilical vessels alpha,beta-methyleneATP was at least 100-fold more potent than ATP. Nucleotide potency was less than that of PGF(2alpha) or endothelin-2, but had the same magnitude as serotonin. ATP-desensitized receptors evidenced cross desensitization to alpha,beta-methyleneATP, 2-MeSATP and diBzATP, effect not observed when desensitization was elicited by alpha,beta-methyleneATP, confirming the presence of various P2X receptor subtypes in the smooth muscles of these vessels. The vasocontractile efficacy of alpha,beta-methyleneATP was unaltered by endothelium removal, while that of ATP was significantly attenuated and those elicited by 2-MeSATP were blunted, indicating the presence of additional endothelial nucleotide receptors. These results suggest that P2X receptors participate in the humoral regulation of placental blood flow.

  6. Concept of an enhanced V2X pedestrian collision avoidance system with a cost function-based pedestrian model.

    PubMed

    Kotte, Jens; Schmeichel, Carsten; Zlocki, Adrian; Gathmann, Hauke; Eckstein, Lutz

    2017-04-03

    Objective State-of-the-art collision avoidance and collision mitigation systems predict the behavior of pedestrians based on trivial models that assume a constant acceleration or velocity. New sources of sensor information, for example smart devices (smartphones, tablets, smartwatches, …), can support enhanced pedestrian behavior models. The objective of this paper is the development and implementation of a V2X pedestrian collision avoidance system that uses new information sources. Methods A literature review of existing state-of-the-art pedestrian collision avoidance systems, pedestrian behavior models in Advanced Driver Assistance Systems (ADAS), and traffic simulations is conducted together with an analysis of existing studies on typical pedestrian patterns in traffic. Based on this analysis, possible parameters for predicting pedestrian behavior were investigated. The results led to new requirements from which a concept was developed and implemented. Results The analysis of typical pedestrian behavior patterns in traffic situations showed the complexity of predicting pedestrian behavior. Requirements for an improved behavior prediction were derived. A concept for a V2X collision avoidance system, based on a cost function that predicts pedestrian near future presence, and its implementation, is presented. The concept presented considers several challenges such as information privacy, inaccuracies of the localization, and inaccuracies of the prediction. Conclusion A concept for an enhanced V2X pedestrian collision avoidance system was developed and introduced. The concept uses new information sources such as smart devices to improve the prediction of the pedestrian's presence in the near future and considers challenges that come along with the usage of these information sources.

  7. Characterisation of P2X receptors expressed in rat pulmonary arteries.

    PubMed

    Syed, Nawazish-i-Husain; Tengah, Asrin; Paul, Andrew; Kennedy, Charles

    2010-12-15

    Previous studies indicated that a P2X receptor other than the P2X1 subtype might be present in rat large, but not small pulmonary arteries. The aim here was to characterise further these P2X receptors. Isometric tension was recorded from rat isolated small (i.d. 250-500 μm) and large pulmonary artery (i.d. 1-1.5 mm) rings mounted on a wire myograph. In both tissues the P2X receptor agonist α,β-meATP evoked rapidly-developing contractions that were inhibited by the P2X antagonists NF449, PPADS and suramin in a concentration-dependent manner and eventually abolished by each. The rank order of the potency in both tissues was NF449>PPADS=suramin. For each antagonist there was no significant difference between its potency in the small and large pulmonary arteries. Prolonged administration of a high concentration of α,β-meATP induced complete desensitisation in both tissues. RT-PCR followed by PCR with specific oligonucleotide primers, identified mRNA for all seven P2X subunits. Subtype-specific antibodies showed strong, punctate P2X1 receptor-like immunoreactivity in the majority of cells and faint, punctate staining with the anti-P2X2 and anti-P2X4 antibodies, whilst P2X5-like immunoreactivity was barely detectable and no P2X3, P2X6, and P2X7 receptor-like immunoreactivity was seen. No differences in P2X mRNA and protein expression were seen between small and large pulmonary arteries. In conclusion, the pharmacological properties and mRNA and protein expression profiles of P2X receptors in rat small and large pulmonary arteries are very similar. Thus P2X1 appears to be the predominant P2X subunit functionally expressed in smooth muscle cells of rat small and large pulmonary arteries.

  8. Role of purinergic P2X4 receptors in regulating striatal dopamine homeostasis and dependent behaviors.

    PubMed

    Khoja, Sheraz; Shah, Vivek; Garcia, Damaris; Asatryan, Liana; Jakowec, Michael W; Davies, Daryl L

    2016-10-01

    Purinergic P2X4 receptors (P2X4Rs) belong to the P2X superfamily of ion channels regulated by ATP. We recently demonstrated that P2X4R knockout (KO) mice exhibited deficits in sensorimotor gating, social interaction, and ethanol drinking behavior. Dopamine (DA) dysfunction may underlie these behavioral changes, but there is no direct evidence for P2X4Rs' role in DA neurotransmission. To test this hypothesis, we measured markers of DA function and dependent behaviors in P2X4R KO mice. P2X4R KO mice exhibited altered density of pre-synaptic markers including tyrosine hydroxylase, dopamine transporter; post-synaptic markers including dopamine receptors and phosphorylation of downstream targets including dopamine and cyclic-AMP regulated phosphoprotein of 32 kDa and cyclic-AMP-response element binding protein in different parts of the striatum. Ivermectin, an allosteric modulator of P2X4Rs, significantly affected dopamine and cyclic AMP regulated phosphoprotein of 32 kDa and extracellular regulated kinase1/2 phosphorylation in the striatum. Sensorimotor gating deficits in P2X4R KO mice were rescued by DA antagonists. Using the 6-hydroxydopamine model of DA depletion, P2X4R KO mice exhibited an attenuated levodopa (L-DOPA)-induced motor behavior, whereas ivermectin enhanced this behavior. Collectively, these findings identified an important role for P2X4Rs in maintaining DA homeostasis and illustrate how this association is important for CNS functions including motor control and sensorimotor gating. We propose that P2X4 receptors (P2X4Rs) regulate dopamine (DA) homeostasis and associated behaviors. Pre-synaptic and post-synaptic DA markers were significantly altered in the dorsal and ventral striatum of P2X4R KO mice, implicating altered DA neurotransmission. Sensorimotor gating deficits in P2X4R KO mice were rescued by DA antagonists. Ivermectin (IVM), a positive modulator of P2X4Rs, enhanced levodopa (L-DOPA)-induced motor behavior. These studies highlight potential

  9. Residual Chemoresponsiveness to Acids in the Superior Laryngeal Nerve in “Taste-Blind” (P2X2/P2X3 Double-KO) Mice

    PubMed Central

    Ohkuri, Tadahiro; Horio, Nao; Stratford, Jennifer M.; Finger, Thomas E.; Ninomiya, Yuzo

    2012-01-01

    Mice lacking both the P2X2 and the P2X3 purinergic receptors (P2X-dblKO) exhibit loss of responses to all taste qualities in the taste nerves innervating the tongue. Similarly, these mice exhibit a near total loss of taste-related behaviors in brief access tests except for a near-normal avoidance of acidic stimuli. This persistent avoidance of acids despite the loss of gustatory neural responses to sour was postulated to be due to continued responsiveness of the superior laryngeal (SL) nerve. However, chemoresponses of the larynx are attributable both to taste buds and to free nerve endings. In order to test whether the SL nerve of P2X-dblKO mice remains responsive to acids but not to other tastants, we recorded responses from the SL nerve in wild-type (WT) and P2X-dblKO mice. WT mice showed substantial SL responses to monosodium glutamate, sucrose, urea, and denatonium—all of which were essentially absent in P2X-dblKO animals. In contrast, the SL nerve of P2X-dblKO mice exhibited near-normal responses to citric acid (50 mM) although responsiveness of both the chorda tympani and the glossopharyngeal nerves to this stimulus were absent or greatly reduced. These results are consistent with the hypothesis that the residual avoidance of acidic solutions by P2X-dblKO mice may be attributable to the direct chemosensitivity of nerve fibers innervating the laryngeal epithelium and not to taste. PMID:22362867

  10. Stable monolayer honeycomb-like structures of RuX2 (X =S,Se)

    NASA Astrophysics Data System (ADS)

    Ersan, Fatih; Cahangirov, Seymur; Gökoǧlu, Gökhan; Rubio, Angel; Aktürk, Ethem

    2016-10-01

    Recent studies show that several metal oxides and dichalcogenides (M X2) , which exist in nature, can be stable in two-dimensional (2D) form and each year several new M X2 structures are explored. The unstable structures in H (hexagonal) or T (octahedral) forms can be stabilized through Peierls distortion. In this paper, we propose new 2D forms of RuS2 and RuSe2 materials. We investigate in detail the stability, electronic, magnetic, optical, and thermodynamic properties of 2D Ru X2 (X =S,Se) structures from first principles. While their H and T structures are unstable, the distorted T structures (T'-Ru X2) are stable and have a nonmagnetic semiconducting ground state. The molecular dynamic simulations also confirm that T'-Ru X2 systems are stable even at 500 K without any structural deformation. T'-RuS2 and T'-RuSe2 have indirect band gaps with 0.745 eV (1.694 eV with HSE) and 0.798 eV (1.675 eV with HSE) gap values, respectively. We also examine their bilayer and trilayer forms and find direct and smaller band gaps. We find that AA stacking is more favorable than the AB configuration. The new 2D materials obtained can be good candidates with striking properties for applications in semiconductor electronic, optoelectronic devices, and sensor technology.

  11. P2X7 deficiency attenuates hypertension and renal injury in deoxycorticosterone acetate-salt hypertension.

    PubMed

    Ji, Xu; Naito, Yukiko; Weng, Huachun; Endo, Kosuke; Ma, Xiao; Iwai, Naoharu

    2012-10-15

    The P2X(7) receptor is a ligand-gated ion channel, and genetic variations in the P2X(7) gene significantly affect blood pressure. P2X(7) receptor expression is associated with renal injury and inflammatory diseases. Uninephrectomized wild-type (WT) and P2X(7)-deficient (P2X(7) KO) mice were subcutaneously implanted with deoxycorticosterone acetate (DOCA) pellets and fed an 8% salt diet for 18 days. Their blood pressure was assessed by a telemetry system. The mice were placed in metabolic cages, and urine was collected for 24 h to assess renal function. After 18 days of DOCA-salt treatment, P2X(7) mRNA and protein expression increased in WT mice. Blood pressure in P2X(7) KO mice was less than that of WT mice (mean systolic blood pressure 133 ± 3 vs. 150 ± 2 mmHg). On day 18, urinary albumin excretion was lower in P2X(7) KO mice than in WT mice (0.11 ± 0.07 vs. 0.28 ± 0.07 mg/day). Creatinine clearance was higher in P2X(7) KO mice than in WT mice (551.53 ± 65.23 vs. 390.85 ± 32.81 μl·min(-1)·g renal weight(-1)). Moreover, renal interstitial fibrosis and infiltration of immune cells (macrophages, T cells, B cells, and leukocytes) were markedly attenuated in P2X(7) KO mice compared with WT mice. The levels of IL-1β, released by macrophages, in P2X(7) KO mice had decreased dramatically compared with that in WT mice. These results strongly suggest that the P2X(7) receptor plays a key role in the development of hypertension and renal disease via increased inflammation, indicating its potential as a novel therapeutic target.

  12. Immunolocalization of the P2X4 receptor on neurons and glia in the mammalian retina.

    PubMed

    Ho, T; Vessey, K A; Fletcher, E L

    2014-09-26

    Extracellular adenosine 5'-triphosphate (eATP) acts as a neurotransmitter within the retina and brain, activating a range of ionotropic P2X and metabotropic P2Y receptors. In this study, the specific localization of the P2X4 receptor (P2X4-R) subunit was evaluated in the retina using fluorescence immunohistochemistry and pre-embedding immuno-electron microscopy. Punctate P2X4-R labeling was largely localized to the inner and outer plexiform layers of mouse, rat and cat retinae. In the mouse outer retina, double-labeling of P2X4-R with the horizontal cell marker, calbindin, revealed P2X4-R immunoreactivity (P2X4-R-IR) on horizontal cell somata and processes. In the inner retina, P2X4-R expression was found closely associated with rod and cone bipolar cell terminals, and the punctate labeling was observed on calretinin-positive amacrine cells. Using immuno-electron microscopy, P2X4-Rs were observed on processes post-synaptic to photoreceptor and bipolar cell terminals, likely representing horizontal, amacrine and ganglion cells, respectively. Furthermore, P2X4-R expression was also observed on Müller cells, astrocytes and microglia. These data suggest a role for P2X4-Rs in the lateral inhibitory pathways of the retina, modulating neuronal function of photoreceptors and bipolar cells. The expression on macro- and microglial cells implicates a role for P2X4-Rs in glial signaling, tissue homeostasis and immunosurveillance within the mammalian retina.

  13. Sociocommunicative and Sensorimotor Impairments in Male P2X4-Deficient Mice

    PubMed Central

    Wyatt, Letisha R; Godar, Sean C; Khoja, Sheraz; Jakowec, Michael W; Alkana, Ronald L; Bortolato, Marco; Davies, Daryl L

    2013-01-01

    Purinergic P2X receptors are a family of ligand-gated ion channels gated by extracellular adenosine 5′-triphosphate (ATP). Of the seven P2X subtypes, P2X4 receptors (P2X4Rs) are richly expressed in the brain, yet their role in behavioral organization remains poorly understood. In this study, we examined the behavioral responses of P2X4R heterozygous (HZ) and knockout (KO) mice in a variety of testing paradigms designed to assess complementary aspects of sensory functions, emotional reactivity, and cognitive organization. P2X4R deficiency did not induce significant alterations of locomotor activity and anxiety-related indices in the novel open field and elevated plus-maze tests. Conversely, P2X4R KO mice displayed marked deficits in acoustic startle reflex amplitude, as well as significant sensorimotor gating impairments, as assessed by the prepulse inhibition of the startle. In addition, P2X4R KO mice displayed enhanced tactile sensitivity, as signified by a lower latency in the sticky-tape removal test. Moreover, both P2X4R HZ and KO mice showed significant reductions in social interaction and maternal separation-induced ultrasonic vocalizations in pups. Notably, brain regions of P2X4R KO mice exhibited significant brain-regional alterations in the subunit composition of glutamate ionotropic receptors. These results collectively document that P2X4-deficient mice exhibit a spectrum of phenotypic abnormalities partially akin to those observed in other murine models of autism-spectrum disorder. In conclusion, our findings highlight a putative role of P2X4Rs in the regulation of perceptual and sociocommunicative functions and point to these receptors as putative targets for disturbances associated with neurodevelopmental disorders. PMID:23604007

  14. Novel Protective Role of Endogenous Cardiac Myocyte P2X4 Receptors in Heart Failure

    PubMed Central

    Yang, Tiehong; Shen, Jian-bing; Yang, Ronghua; Redden, John; Dodge-Kafka, Kimberly; Grady, James; Jacobson, Kenneth A.; Liang, Bruce T.

    2014-01-01

    Background Heart failure (HF), despite continuing progress, remains a leading cause of mortality and morbidity. P2X4 receptors (P2X4R) have emerged as potentially important molecules in regulating cardiac function and as potential targets for HF therapy. Transgenic P2X4R overexpression can protect against HF, but this does not explain the role of native cardiac P2X4R. Our goal is to define the physiological role of endogenous cardiac myocyte P2X4R under basal conditions and during HF induced by myocardial infarction or pressure overload. Methods and Results Mice established with conditional cardiac-specific P2X4R knockout were subjected to left anterior descending coronary artery ligation–induced postinfarct or transverse aorta constriction–induced pressure overload HF. Knockout cardiac myocytes did not show P2X4R by immunoblotting or by any response to the P2X4R-specific allosteric enhancer ivermectin. Knockout hearts showed normal basal cardiac function but depressed contractile performance in postinfarct and pressure overload models of HF by in vivo echocardiography and ex vivo isolated working heart parameters. P2X4R coimmunoprecipitated and colocalized with nitric oxide synthase 3 (eNOS) in wild-type cardiac myocytes. Mice with cardiac-specific P2X4R overexpression had increased S-nitrosylation, cyclic GMP, NO formation, and were protected from postinfarct and pressure overload HF. Inhibitor of eNOS, L-N5-(1-iminoethyl)ornithine hydrochloride, blocked the salutary effect of cardiac P2X4R overexpression in postinfarct and pressure overload HF as did eNOS knockout. Conclusions This study establishes a new protective role for endogenous cardiac myocyte P2X4R in HF and is the first to demonstrate a physical interaction between the myocyte receptor and eNOS, a mediator of HF protection. PMID:24622244

  15. Lipopolysaccharide Inhibits the Channel Activity of the P2X7 Receptor

    PubMed Central

    Leiva-Salcedo, Elias; Coddou, Claudio; Rodríguez, Felipe E.; Penna, Antonello; Lopez, Ximena; Neira, Tanya; Fernández, Ricardo; Imarai, Mónica; Rios, Miguel; Escobar, Jorge; Montoya, Margarita; Huidobro-Toro, J. Pablo; Escobar, Alejandro; Acuña-Castillo, Claudio

    2011-01-01

    The purinergic P2X7 receptor (P2X7R) plays an important role during the immune response, participating in several events such as cytokine release, apoptosis, and necrosis. The bacterial endotoxin lipopolysaccharide (LPS) is one of the strongest stimuli of the immune response, and it has been shown that P2X7R activation can modulate LPS-induced responses. Moreover, a C-terminal binding site for LPS has been proposed. In order to evaluate if LPS can directly modulate the activity of the P2X7R, we tested several signaling pathways associated with P2X7R activation in HEK293 cells that do not express the TLR-4 receptor. We found that LPS alone was unable to induce any P2X7R-related activity, suggesting that the P2X7R is not directly activated by the endotoxin. On the other hand, preapplication of LPS inhibited ATP-induced currents, intracellular calcium increase, and ethidium bromide uptake and had no effect on ERK activation in HEK293 cells. In splenocytes-derived T-regulatory cells, in which ATP-induced apoptosis is driven by the P2X7R, LPS inhibited ATP-induced apoptosis. Altogether, these results demonstrate that LPS modulates the activity of the P2X7R and suggest that this effect could be of physiological relevance. PMID:21941410

  16. Insights into the channel gating of P2X receptors from structures, dynamics and small molecules

    PubMed Central

    Wang, Jin; Yu, Ye

    2016-01-01

    P2X receptors, as ATP-gated non-selective trimeric ion channels, are permeable to Na+, K+ and Ca2+. Comparing with other ligand-gated ion channel families, P2X receptors are distinct in their unique gating properties and pathophysiological roles, and have attracted attention as promising drug targets for a variety of diseases, such as neuropathic pain, multiple sclerosis, rheumatoid arthritis and thrombus. Several small molecule inhibitors for distinct P2X subtypes have entered into clinical trials. However, many questions regarding the gating mechanism of P2X remain unsolved. The structural determinations of P2X receptors at the resting and ATP-bound open states revealed that P2X receptor gating is a cooperative allosteric process involving multiple domains, which marks the beginning of the post-structure era of P2X research at atomic level. Here, we review the current knowledge on the structure-function relationship of P2X receptors, depict the whole picture of allosteric changes during the channel gating, and summarize the active sites that may contribute to new strategies for developing novel allosteric drugs targeting P2X receptors. PMID:26725734

  17. P2X7 receptor knockout prevents streptozotocin-induced type 1 diabetes in mice.

    PubMed

    Vieira, Flávia Sarmento; Nanini, Hayandra Ferreira; Takiya, Christina Maeda; Coutinho-Silva, Robson

    2016-01-05

    Type 1 diabetes (T1D) is caused by autoimmune destruction of islet of Langerhans β-cells. P2X7 receptors (P2X7R) modulate proinflammatory immune responses by binding extracellular ATP, a classic 'danger signal'. Here, we evaluated whether the P2X7R has a role in T1D development. P2X7(-/-) mice are resistant to TD1 induction by streptozotocin (STZ) treatment, with no increase in blood glucose, decrease in insulin-positive cells, and pancreatic islet reduction, compared to WT (C57BL/6) mice. Also, the levels of proinflammatory mediators (IL-1β, IFN-γ and NO) did not increase after STZ treatment in P2X7(-/-) animals, with reduced infiltration of CD4(+), CD8(+), B220(+), CD11b(+) and CD11c(+) cells in the pancreatic lymph nodes. Treatment with a P2X7 antagonist mimicked the effect of P2X7 knockout, preventing STZ-induced diabetes. Our results show that the absence of the P2X7R provides resistance in the induction of diabetes in this model, and suggest that therapy targeting the P2X7R may be useful against clinical T1D.

  18. Accelerated tumor progression in mice lacking the ATP receptor P2X7.

    PubMed

    Adinolfi, Elena; Capece, Marina; Franceschini, Alessia; Falzoni, Simonetta; Giuliani, Anna L; Rotondo, Alessandra; Sarti, Alba C; Bonora, Massimo; Syberg, Susanne; Corigliano, Domenica; Pinton, Paolo; Jorgensen, Niklas R; Abelli, Luigi; Emionite, Laura; Raffaghello, Lizzia; Pistoia, Vito; Di Virgilio, Francesco

    2015-02-15

    The ATP receptor P2X7 (P2X7R or P2RX7) has a key role in inflammation and immunity, but its possible roles in cancer are not firmly established. In the present study, we investigated the effect of host genetic deletion of P2X7R in the mouse on the growth of B16 melanoma or CT26 colon carcinoma cells. Tumor size and metastatic dissemination were assessed by in vivo calliper and luciferase luminescence emission measurements along with postmortem examination. In P2X7R-deficient mice, tumor growth and metastatic spreading were accelerated strongly, compared with wild-type (wt) mice. Intratumoral IL-1β and VEGF release were drastically reduced, and inflammatory cell infiltration was abrogated nearly completely. Similarly, tumor growth was also greatly accelerated in wt chimeric mice implanted with P2X7R-deficient bone marrow cells, defining hematopoietic cells as a sufficient site of P2X7R action. Finally, dendritic cells from P2X7R-deficient mice were unresponsive to stimulation with tumor cells, and chemotaxis of P2X7R-less cells was impaired. Overall, our results showed that host P2X7R expression was critical to support an antitumor immune response, and to restrict tumor growth and metastatic diffusion.

  19. Optical control of trimeric P2X receptors and acid-sensing ion channels.

    PubMed

    Browne, Liam E; Nunes, João P M; Sim, Joan A; Chudasama, Vijay; Bragg, Laricia; Caddick, Stephen; North, R Alan

    2014-01-07

    P2X receptors are trimeric membrane proteins that function as ion channels gated by extracellular ATP. We have engineered a P2X2 receptor that opens within milliseconds by irradiation at 440 nm, and rapidly closes at 360 nm. This requires bridging receptor subunits via covalent attachment of 4,4'-bis(maleimido)azobenzene to a cysteine residue (P329C) introduced into each second transmembrane domain. The cis-trans isomerization of the azobenzene pushes apart the outer ends of the transmembrane helices and opens the channel in a light-dependent manner. Light-activated channels exhibited similar unitary currents, rectification, calcium permeability, and dye uptake as P2X2 receptors activated by ATP. P2X3 receptors with an equivalent mutation (P320C) were also light sensitive after chemical modification. They showed typical rapid desensitization, and they could coassemble with native P2X2 subunits in pheochromocytoma cells to form light-activated heteromeric P2X2/3 receptors. A similar approach was used to open and close human acid-sensing ion channels (ASICs), which are also trimers but are unrelated in sequence to P2X receptors. The experiments indicate that the opening of the permeation pathway requires similar and substantial movements of the transmembrane helices in both P2X receptors and ASICs, and the method will allow precise optical control of P2X receptors or ASICs in intact tissues.

  20. Critical current density and flux pinning in La 2- xPr xCa 2 x Ba 2Cu 4+2 xO z ( x=0.1-0.5) superconductors

    NASA Astrophysics Data System (ADS)

    Rayaprol, S.; Thaker, C. M.; Shah, N. A.; Kuberkar, D. G.

    2004-07-01

    Polycrystalline La 2- xPr xCa 2 xBa 2Cu 4+2 xO z (LPCaBCO) compounds with x=0.1-0.5 were synthesized by solid-state reaction method and studied by room temperature X-ray diffraction, dc resistivity, dc magnetization and iodometry. The superconducting transition temperatures in these tetragonal triple perovskite compounds increases from 32 to 62 K ( Tconset values) with increasing dopant concentration. The mixing of rare earth La 3+ and Pr 3+/4+ ions at rare earth site (La 3+) along with substitution of divalent Ca 2+ results in the shrinkage of unit cell volume. The contraction of unit cell volume due to larger ion being substituted by smaller ions, gives rise to creation of pinning centres in the unit cell leading to increase in critical current density and flux pinning.

  1. P2X4 receptors (P2X4Rs) represent a novel target for the development of drugs to prevent and/or treat alcohol use disorders

    PubMed Central

    Franklin, Kelle M.; Asatryan, Liana; Jakowec, Michael W.; Trudell, James R.; Bell, Richard L.; Davies, Daryl L.

    2014-01-01

    Alcohol use disorders (AUDs) have a staggering socioeconomic impact. Few therapeutic options are available, and they are largely inadequate. These shortcomings highlight the urgent need to develop effective medications to prevent and/or treat AUDs. A critical barrier is the lack of information regarding the molecular target(s) by which ethanol (EtOH) exerts its pharmacological activity. This review highlights findings implicating P2X4 receptors (P2X4Rs) as a target for the development of therapeutics to treat AUDs and discusses the use of ivermectin (IVM) as a potential clinical tool for treatment of AUDs. P2XRs are a family of ligand-gated ion channels (LGICs) activated by extracellular ATP. Of the P2XR subtypes, P2X4Rs are expressed the most abundantly in the CNS. Converging evidence suggests that P2X4Rs are involved in the development and progression of AUDs. First, in vitro studies report that pharmacologically relevant EtOH concentrations can negatively modulate ATP-activated currents. Second, P2X4Rs in the mesocorticolimbic dopamine system are thought to play a role in synaptic plasticity and are located ideally to modulate brain reward systems. Third, alcohol-preferring (P) rats have lower functional expression of the p2rx4 gene than alcohol-non-preferring (NP) rats suggesting an inverse relationship between alcohol intake and P2X4R expression. Similarly, whole brain p2rx4 expression has been shown to relate inversely to innate 24 h alcohol preference across 28 strains of rats. Fourth, mice lacking the p2rx4 gene drink more EtOH than wildtype controls. Fifth, IVM, a positive modulator of P2X4Rs, antagonizes EtOH-mediated inhibition of P2X4Rs in vitro and reduces EtOH intake and preference in vivo. These findings suggest that P2X4Rs contribute to EtOH intake. The present review summarizes recent findings focusing on the P2X4R as a molecular target of EtOH action, its role in EtOH drinking behavior and modulation of its activity by IVM as a potential therapy

  2. Targeting of the P2X7 receptor in pancreatic cancer and stellate cells

    PubMed Central

    Giannuzzo, Andrea; Saccomano, Mara; Napp, Joanna; Ellegaard, Maria; Alves, Frauke

    2016-01-01

    The ATP‐gated receptor P2X7 (P2X7R) is involved in regulation of cell survival and has been of interest in cancer field. Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer and new markers and therapeutic targets are needed. PDAC is characterized by a complex tumour microenvironment, which includes cancer and pancreatic stellate cells (PSCs), and potentially high nucleotide/side turnover. Our aim was to determine P2X7R expression and function in human pancreatic cancer cells in vitro as well as to perform in vivo efficacy study applying P2X7R inhibitor in an orthotopic xenograft mouse model of PDAC. In the in vitro studies we show that human PDAC cells with luciferase gene (PancTu‐1 Luc cells) express high levels of P2X7R protein. Allosteric P2X7R antagonist AZ10606120 inhibited cell proliferation in basal conditions, indicating that P2X7R was tonically active. Extracellular ATP and BzATP, to which the P2X7R is more sensitive, further affected cell survival and confirmed complex functionality of P2X7R. PancTu‐1 Luc migration and invasion was reduced by AZ10606120, and it was stimulated by PSCs, but not by PSCs from P2X7‐/‐ animals. PancTu‐1 Luc cells were orthotopically transplanted into nude mice and tumour growth was followed noninvasively by bioluminescence imaging. AZ10606120‐treated mice showed reduced bioluminescence compared to saline‐treated mice. Immunohistochemical analysis confirmed P2X7R expression in cancer and PSC cells, and in metaplastic/neoplastic acinar and duct structures. PSCs number/activity and collagen deposition was reduced in AZ10606120‐treated tumours. PMID:27513892

  3. The effect of anions on the human P2X7 receptor.

    PubMed

    Kubick, Christoph; Schmalzing, Günther; Markwardt, Fritz

    2011-12-01

    P2X7 receptors (P2X7Rs) are nonselective cation channels that are opened by the binding of extracellular ATP and are involved in the modulation of epithelial secretion, inflammation and nociception. Here, we investigated the effect of extracellular anions on channel gating and permeation of human P2X7Rs (hP2X7Rs) expressed in Xenopus laevis oocytes. Two-microelectrode voltage-clamp recordings showed that ATP-induced hP2X7R-mediated currents increased when extracellular chloride was substituted by the organic anions glutamate or aspartate and decreased when chloride was replaced by the inorganic anions nitrate, sulfate or iodide. ATP concentration-response comparisons revealed that substitution of chloride by glutamate decreased agonist efficacy, while substitution by iodide increased agonist efficacy at high ATP concentrations. Meanwhile, the ATP potency remained unchanged. Activation of the hP2X7R at low ATP concentrations via the high-affinity ATP effector site was not affected by the replacement of chloride by glutamate or iodide. To analyze the anion effect on the hP2X7R at the single-molecule level, we performed single-channel current measurements using the patch-clamp technique in the outside-out configuration. Chloride substitution did not affect the single-channel conductance, but the probability that the P2X7R channel was open increased when chloride was replaced by glutamate and decreased when chloride was replaced by iodide. This effect was due to an influence of the anions on the mean closed times of the hP2X7R channel. We conclude that hP2X7R channels are not anion-permeable in physiological Na+-based media and that external anions allosterically affect ion channel opening in the fully ATP4-liganded P2X7R through an extracellular anion binding site.

  4. Caveolin-1 regulates P2X7 receptor signaling in osteoblasts.

    PubMed

    Gangadharan, Vimal; Nohe, Anja; Caplan, Jeffrey; Czymmek, Kirk; Duncan, Randall L

    2015-01-01

    The synthesis of new bone in response to a novel applied mechanical load requires a complex series of cellular signaling events in osteoblasts and osteocytes. The activation of the purinergic receptor P2X(7)R is central to this mechanotransduction signaling cascade. Recently, P2X(7)R have been found to be associated with caveolae, a subset of lipid microdomains found in several cell types. Deletion of caveolin-1 (CAV1), the primary protein constituent of caveolae in osteoblasts, results in increased bone mass, leading us to hypothesize that the P2X(7)R is scaffolded to caveolae in osteoblasts. Thus, upon activation of the P2X(7)R, we postulate that caveolae are endocytosed, thereby modulating the downstream signal. Sucrose gradient fractionation of MC3T3-E1 preosteoblasts showed that CAV1 was translocated to the denser cytosolic fractions upon stimulation with ATP. Both ATP and the more specific P2X(7)R agonist 2'(3')-O-(4-benzoylbenzoyl)ATP (BzATP) induced endocytosis of CAV1, which was inhibited when MC3T3-E1 cells were pretreated with the specific P2X7R antagonist A-839977. The P2X7R cofractionated with CAV1, but, using superresolution structured illumination microscopy, we found only a subpopulation of P2X(7)R in these lipid microdomains on the membrane of MC3T3-E1 cells. Suppression of CAV1 enhanced the intracellular Ca(2+) response to BzATP, suggesting that caveolae regulate P2X(7)R signaling. This proposed mechanism is supported by increased mineralization in CAV1 knockdown MC3T3-E1 cells treated with BzATP. These data suggest that caveolae regulate P2X(7)R signaling upon activation by undergoing endocytosis and potentially carrying with it other signaling proteins, hence controlling the spatiotemporal signaling of P2X(7)R in osteoblasts.

  5. Expression of the apoptotic calcium channel P2X7 in the glandular epithelium.

    PubMed

    Slater, Michael; Danieletto, Suzanne; Barden, Julian A

    2005-03-01

    In the current study, expression of the apoptotic calcium channel receptor P2X(7) and prostate-specific antigen (PSA) levels were studied in biopsy cores from 174 patients as well as 20 radical prostatectomy cases. In clinical biopsies, we have previously demonstrated that P2X(1 )and P2X(2) calcium channel receptors are absent from normal prostate epithelium that does not progress to prostate cancer within 5 years. In cases that did progress to prostate cancer however, P2X(1 )and P2X(2) labeling was observed in a stage-specific manner first in the nucleus, then the cytoplasm and finally on the apical epithelium, as prostate cancer developed. These markers were present up to 5 years before cancer was detectable by the usual morphological criteria (Gleason grading) as determined by H and E staining. In the current study, the apoptotic calcium channel receptor P2X(7) yielded similar results to that of P2X(1) and P2X(2). Using radical prostatectomy tissue sections as well as biopsies, these changes in calcium channel metabolism were noted throughout the prostate, indicating a field effect. This finding suggests that the presence of a prostate tumor could be detected without the need for direct sampling of tumor tissue, leading to detection of false negative cases missed by H or E stain. The reliability of PSA levels as a prognostic indicator has been questioned in recent years. In the current study, PSA levels were correlated with the P2X(7) labeling results. All patients who exhibited no P2X(7) labeling had a prostatic serum antigen (PSA) level of <2. Patients who exhibited stage-specific P2X(7) expression, and who later developed obvious prostate cancer as diagnosed by H and E stain, all had a PSA > 2. This finding suggests that increasing PSA may be an accurate indicator of cancer development.

  6. Involvement of the P2X7-NLRP3 axis in leukemic cell proliferation and death

    PubMed Central

    Salaro, Erica; Rambaldi, Alessia; Falzoni, Simonetta; Amoroso, Francesca Saveria; Franceschini, Alessia; Sarti, Alba Clara; Bonora, Massimo; Cavazzini, Francesco; Rigolin, Gian Matteo; Ciccone, Maria; Audrito, Valentina; Deaglio, Silvia; Pelegrin, Pablo; Pinton, Paolo; Cuneo, Antonio; Di Virgilio, Francesco

    2016-01-01

    Lymphocyte growth and differentiation are modulated by extracellular nucleotides and P2 receptors. We previously showed that the P2X7 receptor (P2X7R or P2RX7) is overexpressed in circulating lymphocytes from chronic lymphocytic leukemia (CLL) patients. In the present study we investigated the P2X7R/NLRP3 inflammasome axis in lymphocytes from a cohort of 23 CLL patients. P2X7R, ASC and NLRP3 were investigated by Western blot, PCR and transfection techniques. P2X7R was overexpressed and correlated with chromosome 12 trisomy in CLL patients. ASC mRNA and protein were also overexpressed. On the contrary, NLRP3 was dramatically down-modulated in CLL lymphocytes relative to lymphocytes from healthy donors. To further investigate the correlation between P2X7R, NLRP3 and cell growth, NLRP3 was silenced in THP-1 cells, a leukemic cell line that natively expresses both NLRP3 and P2X7R. NLRP3 silencing enhanced P2X7R expression and promoted growth. On the contrary, NLRP3 overexpression caused accelerated apoptosis. The P2X7R was also up-modulated in hematopoietic cells from NLRP3-KO mice. In conclusion, we show that NLRP3 down-modulation stimulates P2X7R expression and promotes growth, while NLRP3 overexpression inhibits cell proliferation and stimulates apoptosis. These findings suggest that NLRP3 is a negative regulator of growth and point to a role of the P2X7R/NLRP3 axis in CLL. PMID:27221966

  7. Human neutrophils do not express purinergic P2X7 receptors

    PubMed Central

    Martel-Gallegos, Guadalupe; Rosales-Saavedra, María T.; Reyes, Juan P.; Casas-Pruneda, Griselda; Toro-Castillo, Carmen; Pérez-Cornejo, Patricia

    2010-01-01

    It has been reported that in human neutrophils, external ATP activates plasma membrane purinergic P2X7 receptors (P2X7R) to elicit Ca2+ entry, production of reactive oxygen species (ROS), processing and release of pro-inflammatory cytokines, shedding of adhesion molecules and uptake of large molecules. However, the expression of P2X7R at the plasma membrane of neutrophils has also been questioned since these putative responses are not always reproduced. In this work, we used electrophysiological recordings to measure functional responses associated with the activation of membrane receptors, spectrofluorometric measurements of ROS production and ethidium bromide uptake to asses coupling of P2X7R activation to downstream effectors, immune-labelling of P2X7R using a fluorescein isothiocyanate-conjugated antibody to detect the receptors at the plasma membrane, RT-PCR to determine mRNA expression of P2X7R and Western blot to determine protein expression in neutrophils and HL-60 cells. None of these assays reported the presence of P2X7R in the plasma membrane of neutrophils and non-differentiated or differentiated HL-60 cells—a model cell for human neutrophils. We concluded that P2X7R are not present at plasma membrane of human neutrophils and that the putative physiological responses triggered by external ATP should be reconsidered. PMID:21103213

  8. Nociceptive transmission and modulation via P2X receptors in central pain syndrome.

    PubMed

    Kuan, Yung-Hui; Shyu, Bai-Chuang

    2016-05-26

    Painful sensations are some of the most frequent complaints of patients who are admitted to local medical clinics. Persistent pain varies according to its causes, often resulting from local tissue damage or inflammation. Central somatosensory pathway lesions that are not adequately relieved can consequently cause central pain syndrome or central neuropathic pain. Research on the molecular mechanisms that underlie this pathogenesis is important for treating such pain. To date, evidence suggests the involvement of ion channels, including adenosine triphosphate (ATP)-gated cation channel P2X receptors, in central nervous system pain transmission and persistent modulation upon and following the occurrence of neuropathic pain. Several P2X receptor subtypes, including P2X2, P2X3, P2X4, and P2X7, have been shown to play diverse roles in the pathogenesis of central pain including the mediation of fast transmission in the peripheral nervous system and modulation of neuronal activity in the central nervous system. This review article highlights the role of the P2X family of ATP receptors in the pathogenesis of central neuropathic pain and pain transmission. We discuss basic research that may be translated to clinical application, suggesting that P2X receptors may be treatment targets for central pain syndrome.

  9. Nb doping effect on TiO2-x films for bolometer applications

    NASA Astrophysics Data System (ADS)

    Shin, Young Bong; Kumar Reddy, Y. Ashok; Kang, In-Ku; Lee, Hee Chul

    2016-04-01

    Nb-doped TiO2-x thin films were deposited using a 1 at% niobium doped titanium target by RF reactive magnetron sputtering at various oxygen partial pressures (pO2). The films appeared amorphous in the pO2 range of 4.4-4.7% with resistivity ranging from 0.39 Ω cm to 2.48 Ω cm. Compared to pure TiO2-x films, the resistivity of the Nb-doped TiO2-x films did not change sensitively with the oxygen partial pressure, indicating that the resistivity of the films can be accurately controlled. 1/f noise parameter of Nb-doped TiO2-x films were found to decrease largely while the measured temperature coefficient of resistance (TCR) of the films was still high. The obtained results indicate that Nb-doped TiO2-x films have great potential as an alternative bolometric material.

  10. P2X receptors as targets for the treatment of status epilepticus

    PubMed Central

    Henshall, David C.; Diaz-Hernandez, Miguel; Miras-Portugal, M. Teresa; Engel, Tobias

    2013-01-01

    Prolonged seizures are amongst the most common neurological emergencies. Status epilepticus is a state of continuous seizures that is life-threatening and prompt termination of status epilepticus is critical to protect the brain from permanent damage. Frontline treatment comprises parenteral administration of anticonvulsants such as lorazepam that facilitate γ-amino butyric acid (GABA) transmission. Because status epilepticus can become refractory to anticonvulsants in a significant proportion of patients, drugs which act on different neurotransmitter systems may represent potential adjunctive treatments. P2X receptors are a class of ligand-gated ion channel activated by ATP that contributes to neuro- and glio-transmission. P2X receptors are expressed by both neurons and glia in various brain regions, including the hippocampus. Electrophysiology, pharmacology and genetic studies suggest certain P2X receptors are activated during pathologic brain activity. Expression of several members of the family including P2X2, P2X4, and P2X7 receptors has been reported to be altered in the hippocampus following status epilepticus. Recent studies have shown that ligands of the P2X7 receptor can have potent effects on seizure severity during status epilepticus and mice lacking this receptor display altered seizures in response to chemoconvulsants. Antagonists of the P2X7 receptor also modulate neuronal death, microglial responses and neuroinflammatory signaling. Recent work also found altered neuronal injury and inflammation after status epilepticus in mice lacking the P2X4 receptor. In summary, members of the P2X receptor family may serve important roles in the pathophysiology of status epilepticus and represent novel targets for seizure control and neuroprotection. PMID:24324404

  11. Immunohistochemical identification of cells expressing ATP-gated cation channels (P2X receptors) in the adult rat thyroid

    PubMed Central

    GLASS, RAINER; BURNSTOCK, GEOFFREY

    2001-01-01

    We carried out immunohistochemistry and western blotting of fresh frozen sections and crude extracts from adult rat thyroids. The histochemical and immunoblotting studies were performed with P2X receptor antibodies from 2 different sources. P2X-immunopositive cells were identified by fluorescence double labelling and confocal microscopy. Results of the western blotting experiments showed double bands of approximately 70 kDa and 140 kDa for all 7 P2X receptor subtypes with both sets of antibodies. Histochemical stains with antibodies from both sources also gave essentially identical results. P2X1, P2X2 and P2X6 receptors were detected exclusively in vascular smooth muscle; P2X5 and P2X7 receptors were also present on vascular smooth muscle. Endothelial cells stained for P2X3, P2X4 and P2X7 receptors. Thyroid follicular cells displayed immunoreactivity for P2X3, P2X4 and P2X5 receptors. No immunostaining for P2X receptors was observed on C-cells. Possible roles for the broad expression of P2X receptor subtypes in the rat thyroid are discussed. PMID:11430696

  12. Spin-stripe density varies linearly with the hole content in single-layer Bi2+xSr2-xCuO6+y cuprate superconductors.

    PubMed

    Enoki, M; Fujita, M; Nishizaki, T; Iikubo, S; Singh, D K; Chang, S; Tranquada, J M; Yamada, K

    2013-01-04

    We have performed inelastic neutron scattering measurements on the single-layer cuprate Bi(2+x) Sr(2-x) CuO(6+y) (Bi2201) with x = 0.2, 0.3, 0.4, and 0.5, a doping range that spans the spin-glass to superconducting phase boundary. The doping evolution of low energy spin fluctuations (11 2-x) Sr(x)CuO(4) are discussed.

  13. Spin-Stripe Density Varies Linearly With the Hole Content in Single-Layer Bi2+xSr2-xCuO6+y Cuprate Superconductors

    NASA Astrophysics Data System (ADS)

    Enoki, M.; Fujita, M.; Nishizaki, T.; Iikubo, S.; Singh, D. K.; Chang, S.; Tranquada, J. M.; Yamada, K.

    2013-01-01

    We have performed inelastic neutron scattering measurements on the single-layer cuprate Bi2+xSr2-xCuO6+y (Bi2201) with x=0.2, 0.3, 0.4, and 0.5, a doping range that spans the spin-glass to superconducting phase boundary. The doping evolution of low energy spin fluctuations (≲11meV) was found to be characterized by a change in the incommensurate modulation wave vector from the tetragonal [110] to [100]/[010] directions, while maintaining a linear relation between the incommensurability and the hole concentration, δ≈p. In the superconducting regime, the spectral weight is strongly suppressed below ˜4meV. Similarities and differences in the spin correlations between Bi2201 and the prototypical single-layer system La2-xSrxCuO4 are discussed.

  14. Modulation of bladder afferent signals in normal and spinal cord-injured rats by purinergic P2X3 and P2X2/3 receptors

    PubMed Central

    Munoz, Alvaro; Somogyi, George T.; Boone, Timothy B.; Ford, Anthony P.; Smith, Christopher P.

    2015-01-01

    OBJECTIVE • To evaluate the role of bladder sensory purinergic P2X3 and P2X2/3 receptors on modulating the activity of lumbosacral neurones and urinary bladder contractions in vivo in normal or spinal cord-injured (SCI) rats with neurogenic bladder overactivity. MATERIALS AND METHODS • SCI was induced in female rats by complete transection at T8 – T9 and experiments were performed 4 weeks later, when bladder overactivity developed. Non-transected rats were used as controls (normal rats). • Neural activity was recorded in the dorsal horn of the spinal cord and field potentials were acquired in response to intravesical pressure steps via a suprapubic catheter. Field potentials were recorded under control conditions, after stimulation of bladder mucosal purinergic receptors with intravesical ATP (1 mm), and after intravenous injection of the P2X3/P2X2/3 antagonist AF-353 (10 mg/kg and 20 mg/kg). • Cystometry was performed in urethaneanaesthetised rats intravesically infused with saline. AF-353 (10 mg/kg) was systemically applied after baseline recordings; the rats also received a second dose of AF-353 (20 mg/kg). Changes in the frequency of voiding (VC) and non-voiding (NVC) contractions were evaluated. RESULTS • SCI rats had significantly higher frequencies for field potentials and NVC than NL rats. Intravesical ATP increased field potential frequency in control but not SCI rats, while systemic AF-353 significantly reduced this parameter in both groups. • AF-353 also reduced the inter-contractile interval in control but not in SCI rats; however, the frequency of NVC in SCI rats was significantly reduced. CONCLUSION • The P2X3/P2X2/3 receptors on bladder afferent nerves positively regulate sensory activity and NVCs in overactive bladders. PMID:22540742

  15. [Effect of Zhuangyao Jianshen Wan (ZYJCW) on P2X1 and P2X3 mRNA expressions in rats with diuresis caused by kidney deficiency].

    PubMed

    Chen, Jia-yi; Jiang, Wei-wen; He, Feng-lei; Mo, Guo-qiang; Guo, Zhong-hui; Wang, Xiao-dan; Wu, Qing-he; Cao, Hong-yin

    2015-08-01

    To investigate the urination-reducing effect and mechanism of Zhuangyao Jianshen Wan (ZYJCW). In this study, SI rats were subcutaneously injected with 150 mg · kg(-1) dose of D-galactose to prepare the sub-acute aging model and randomly divided into the model group, the Suoquan Wan group (1.17 g · kg(-1) · d(-1)), and ZYJCW high, medium and low dose groups (2.39, 1.20, 0.60 g · kg(-1) · d(-1)) , with normal rats in the blank group. They were continuously administered with drugs for eight weeks. The metabolic cage method was adopted to measure the 24 h urine volume and 5 h water load urine volume in rats. The automatic biochemistry analyzer was adopted to detect urine concentrations of Na+, Cl-, K+. The ELISA method was used to determine serum aldosterone (ALD) and antidiuretic hormone (ADH). The changes in P2X1 and P2X3 mRNA expressions in bladder tissues of rats were detected by RT-PCR. According to the results, both ZYJCW high and medium dose groups showed significant down-regulations in 24 h urine volume and 5 h water load urine volume in (P <0.05, P <0.01), declines in Na+ and Cl- concentrations in urine (P <0.01), notable rises in plasma ALD and ADH contents (P <0.05, P <0.01) and remarkable down-regulations in the P2X1 and P2X3 mRNA expressions in bladder tissues (P <0.01). The ZYJCW low dose group revealed obvious reductions in Na+ and Cl- concentrations in urine (P <0.01). The results indicated that ZYJCW may show the urination-reducing effect by down-regulating the P2X1 and P2X3 mRNA expressions in bladder tissues of rats with diuresis caused by kidney deficiency.

  16. Controlling the electronic structure of Co1-xFe2+xO4 thin films through iron doping

    SciTech Connect

    Moyer, J.A.; Arena, D.; Vaz, C.A.F.; Negusse, E.; Henrich, V.E.

    2011-01-19

    The electronic, magnetic and transport properties of iron-doped cobalt ferrite (Co{sub 1-x}Fe{sub 2+x}O{sub 4}) thin films grown epitaxially on MgO (001) substrates are investigated by soft x-ray absorption and photoelectron spectroscopy, ultraviolet photoelectron spectroscopy, superconducting quantum interference device magnetometry, and resistivity measurements. The crystal structure for Co{sub 1-x}Fe{sub 2+x}O{sub 4} is determined to be nearly inverse spinel, with the degree of inversion increasing for increased doping until it becomes fully inverse spinel for Fe{sub 3}O{sub 4}. The doped iron cations have a valency of 2+ and reside solely on octahedral sites, which allows for conduction owing to hopping between Fe{sup 2+} and Fe{sup 3+} octahedral cations. The addition of Fe{sup 2+} cations increases the electron density of states near the Fermi energy, shifting the Fermi level from 0.75 to 0 eV with respect to the top of the valence band, as the doping increases from x = 0.01 to 1. This change in electronic structure results in a change in resistivity by over two orders of magnitude. In contrast, the magnetic properties of CoFe{sub 2}O{sub 4} thin films, characterized by a significantly reduced saturation magnetization compared to the bulk and large magnetic anisotropies, are affected less significantly by doping in the range from 0 to 0.63. These results show that Co{sub 1-x}Fe{sub 2+x}O{sub 4} has tunable electronic properties while maintaining magnetic properties similar to CoFe{sub 2}O{sub 4}.

  17. Self-assembly of [UO2X4]2- (X=Cl, Br) dianions with γ substituted pyridinium cations: Structural systematics and fluorescence properties

    NASA Astrophysics Data System (ADS)

    Surbella, Robert G.; Andrews, Michael B.; Cahill, Christopher L.

    2016-04-01

    Room temperature self-assembly of [UO2X4]2- (X=Cl, Br) with γ substituted pyridinium cations has resulted in the formation of twelve compounds that were studied via single crystal X-ray diffraction and fluorescence spectroscopy. Systematic variation of electron donating groups on the pyridinium species is shown to influence the presence and/or strength of various supramolecular synthons, including hydrogen bonding and pi interactions. Combinations of such non-covalent interactions (NCIs) have given rise to a range of supramolecular assemblies, and are shown to influence uranyl emission by way of second sphere coordination to equatorial ligands.

  18. Enhancement of Magnetoelectric Coupling in CoGaxFe2-xO4/BaTiO3 Composite

    NASA Astrophysics Data System (ADS)

    Ni, Yan; Zhang, Zhen; Jiles, David; Nlebedim, Cajetan

    2015-03-01

    Multiferroic materials exhibit magnetoelectric coupling and promise new device applications including magnetic sensors, generators and filters. An effective method for developing magnetoelectric (ME) materials with enhanced ME effect is achieved by the coupling through the interfacial strain between piezoelectric and magnetostrictive materials. In this study, enhancement of magnetoelectric coupling was found by systematically studying the electrical and magnetic properties of CoGaxFe2-xO4/BaTiO3 composite. It is found that Ga doping not only stabilizes the magnetic phase of composites but also increases the sensitivity of magnetoelastic response by 30%. Moreover, Ga doping reduces the electrical conductivity and the dielectric loss of composite. An enhancement of the electrostrain with doping Ga is also observed in CoGaxFe2-xO4/BaTiO3 (x =0.3). As both the sensitivity of magnetostriction and the change in the electric field with strain increase, the ME voltage coefficient also increase. Thus, our work is beneficial for the application of CoFe2O4/BaTiO3-based multiferroic materials. This work was supported by the USDoE, Office of Science, Basic Energy Sciences, Materials Science and Engineering Division. The research was performed at Ames Laboratory, operated for the USDoE by Iowa State University (contract # DE-AC02-07CH11358)

  19. Use-dependent inhibition of P2X3 receptors by nanomolar agonist.

    PubMed

    Pratt, Emily B; Brink, Thaddeus S; Bergson, Pamela; Voigt, Mark M; Cook, Sean P

    2005-08-10

    P2X3 receptors desensitize within 100 ms of channel activation, yet recovery from desensitization requires several minutes. The molecular basis for this slow rate of recovery is unknown. We designed experiments to test the hypothesis that this slow recovery is attributable to the high affinity (< 1 nM) of desensitized P2X3 receptors for agonist. We found that agonist binding to the desensitized state provided a mechanism for potent inhibition of P2X3 current. Sustained applications of 0.5 nM ATP inhibited > 50% of current to repetitive applications of P2X3 agonist. Inhibition occurred at 1000-fold lower agonist concentrations than required for channel activation and showed strong use dependence. No inhibition occurred without previous activation and desensitization. Our data are consistent with a model whereby inhibition of P2X3 by nanomolar [agonist] occurs by the rebinding of agonist to desensitized channels before recovery from desensitization. For several ATP analogs, the concentration required to inhibit P2X3 current inversely correlated with the rate of recovery from desensitization. This indicates that the affinity of the desensitized state and recovery rate primarily depend on the rate of agonist unbinding. Consistent with this hypothesis, unbinding of [32P]ATP from desensitized P2X3 receptors mirrored the rate of recovery from desensitization. As expected, disruption of agonist binding by site-directed mutagenesis increased the IC50 for inhibition and increased the rate of recovery.

  20. Involvement of P2X7 receptor in neuronal degeneration triggered by traumatic injury

    PubMed Central

    Nadal-Nicolás, Francisco M.; Galindo-Romero, Caridad; Valiente-Soriano, Francisco J.; Barberà-Cremades, María; deTorre-Minguela, Carlos; Salinas-Navarro, Manuel; Pelegrín, Pablo; Agudo-Barriuso, Marta

    2016-01-01

    Axonal injury is a common feature of central nervous system insults that culminates with the death of the affected neurons, and an irreversible loss of function. Inflammation is an important component of the neurodegenerative process, where the microglia plays an important role by releasing proinflammatory factors as well as clearing the death neurons by phagocytosis. Here we have identified the purinergic signaling through the P2X7 receptor as an important component for the neuronal death in a model of optic nerve axotomy. We have found that in P2X7 receptor deficient mice there is a delayed loss of retinal ganglion cells and a decrease of phagocytic microglia at early times points after axotomy. In contralateral to the axotomy retinas, P2X7 receptor controlled the numbers of phagocytic microglia, suggesting that extracellular ATP could act as a danger signal activating the P2X7 receptor in mediating the loss of neurons in contralateral retinas. Finally, we show that intravitreal administration of the selective P2X7 receptor antagonist A438079 also delays axotomy-induced retinal ganglion cell death in retinas from wild type mice. Thus, our work demonstrates that P2X7 receptor signaling is involved in neuronal cell death after axonal injury, being P2X7 receptor antagonism a potential therapeutic strategy. PMID:27929040

  1. Blockade of P2X7 receptors or pannexin-1 channels similarly attenuates postischemic damage

    PubMed Central

    Cisneros-Mejorado, Abraham; Gottlieb, Miroslav; Cavaliere, Fabio; Magnus, Tim; Koch-Nolte, Friederich; Scemes, Eliana; Pérez-Samartín, Alberto; Matute, Carlos

    2015-01-01

    The role of P2X7 receptors and pannexin-1 channels in ischemic damage remains controversial. Here, we analyzed their contribution to postanoxic depolarization after ischemia in cultured neurons and in brain slices. We observed that pharmacological blockade of P2X7 receptors or pannexin-1 channels delayed the onset of postanoxic currents and reduced their slope, and that simultaneous inhibition did not further enhance the effects of blocking either one. These results were confirmed in acute cortical slices from P2X7 and pannexin-1 knockout mice. Oxygen-glucose deprivation in cortical organotypic cultures caused neuronal death that was reduced with P2X7 and pannexin-1 blockers as well as in organotypic cultures derived from mice lacking P2X7 and pannexin 1. Subsequently, we used transient middle cerebral artery occlusion to monitor the neuroprotective effect of those drugs in vivo. We found that P2X7 and pannexin-1 antagonists, and their ablation in knockout mice, substantially attenuated the motor symptoms and reduced the infarct volume to ~50% of that in vehicle-treated or wild-type animals. These results show that P2X7 receptors and pannexin-1 channels are major mediators of postanoxic depolarization in neurons and of brain damage after ischemia, and that they operate in the same deleterious signaling cascade leading to neuronal and tissue demise. PMID:25605289

  2. Blockade of P2X7 receptors or pannexin-1 channels similarly attenuates postischemic damage.

    PubMed

    Cisneros-Mejorado, Abraham; Gottlieb, Miroslav; Cavaliere, Fabio; Magnus, Tim; Koch-Nolte, Friederich; Scemes, Eliana; Pérez-Samartín, Alberto; Matute, Carlos

    2015-05-01

    The role of P2X7 receptors and pannexin-1 channels in ischemic damage remains controversial. Here, we analyzed their contribution to postanoxic depolarization after ischemia in cultured neurons and in brain slices. We observed that pharmacological blockade of P2X7 receptors or pannexin-1 channels delayed the onset of postanoxic currents and reduced their slope, and that simultaneous inhibition did not further enhance the effects of blocking either one. These results were confirmed in acute cortical slices from P2X7 and pannexin-1 knockout mice. Oxygen-glucose deprivation in cortical organotypic cultures caused neuronal death that was reduced with P2X7 and pannexin-1 blockers as well as in organotypic cultures derived from mice lacking P2X7 and pannexin 1. Subsequently, we used transient middle cerebral artery occlusion to monitor the neuroprotective effect of those drugs in vivo. We found that P2X7 and pannexin-1 antagonists, and their ablation in knockout mice, substantially attenuated the motor symptoms and reduced the infarct volume to ~50% of that in vehicle-treated or wild-type animals. These results show that P2X7 receptors and pannexin-1 channels are major mediators of postanoxic depolarization in neurons and of brain damage after ischemia, and that they operate in the same deleterious signaling cascade leading to neuronal and tissue demise.

  3. P2X7 receptors trigger ATP exocytosis and modify secretory vesicle dynamics in neuroblastoma cells.

    PubMed

    Gutiérrez-Martín, Yolanda; Bustillo, Diego; Gómez-Villafuertes, Rosa; Sánchez-Nogueiro, Jesús; Torregrosa-Hetland, Cristina; Binz, Thomas; Gutiérrez, Luis Miguel; Miras-Portugal, María Teresa; Artalejo, Antonio R

    2011-04-01

    Previously, we reported that purinergic ionotropic P2X7 receptors negatively regulate neurite formation in Neuro-2a (N2a) mouse neuroblastoma cells through a Ca(2+)/calmodulin-dependent kinase II-related mechanism. In the present study we used this cell line to investigate a parallel though faster P2X7 receptor-mediated signaling pathway, namely Ca(2+)-regulated exocytosis. Selective activation of P2X7 receptors evoked exocytosis as assayed by high resolution membrane capacitance measurements. Using dual-wavelength total internal reflection microscopy, we have observed both the increase in near-membrane Ca(2+) concentration and the exocytosis of fluorescently labeled vesicles in response to P2X7 receptor stimulation. Moreover, activation of P2X7 receptors also affects vesicle motion in the vertical and horizontal directions, thus, involving this receptor type in the control of early steps (docking and priming) of the secretory pathway. Immunocytochemical and RT-PCR experiments evidenced that N2a cells express the three neuronal SNAREs as well as vesicular nucleotide and monoamine (VMAT-1 and VMAT-2) transporters. Biochemical measurements indicated that ionomycin induced a significant release of ATP from N2a cells. Finally, P2X7 receptor stimulation and ionomycin increased the incidence of small transient inward currents, reminiscent of postsynaptic quantal events observed at synapses. Small transient inward currents were dependent on extracellular Ca(2+) and were abolished by Brilliant Blue G, suggesting they were mediated by P2X7 receptors. Altogether, these results suggest the existence of a positive feedback mechanism mediated by P2X7 receptor-stimulated exocytotic release of ATP that would act on P2X7 receptors on the same or neighbor cells to further stimulate its own release and negatively control N2a cell differentiation.

  4. P2X7 Receptors Trigger ATP Exocytosis and Modify Secretory Vesicle Dynamics in Neuroblastoma Cells*

    PubMed Central

    Gutiérrez-Martín, Yolanda; Bustillo, Diego; Gómez-Villafuertes, Rosa; Sánchez-Nogueiro, Jesús; Torregrosa-Hetland, Cristina; Binz, Thomas; Gutiérrez, Luis Miguel; Miras-Portugal, María Teresa; Artalejo, Antonio R.

    2011-01-01

    Previously, we reported that purinergic ionotropic P2X7 receptors negatively regulate neurite formation in Neuro-2a (N2a) mouse neuroblastoma cells through a Ca2+/calmodulin-dependent kinase II-related mechanism. In the present study we used this cell line to investigate a parallel though faster P2X7 receptor-mediated signaling pathway, namely Ca2+-regulated exocytosis. Selective activation of P2X7 receptors evoked exocytosis as assayed by high resolution membrane capacitance measurements. Using dual-wavelength total internal reflection microscopy, we have observed both the increase in near-membrane Ca2+ concentration and the exocytosis of fluorescently labeled vesicles in response to P2X7 receptor stimulation. Moreover, activation of P2X7 receptors also affects vesicle motion in the vertical and horizontal directions, thus, involving this receptor type in the control of early steps (docking and priming) of the secretory pathway. Immunocytochemical and RT-PCR experiments evidenced that N2a cells express the three neuronal SNAREs as well as vesicular nucleotide and monoamine (VMAT-1 and VMAT-2) transporters. Biochemical measurements indicated that ionomycin induced a significant release of ATP from N2a cells. Finally, P2X7 receptor stimulation and ionomycin increased the incidence of small transient inward currents, reminiscent of postsynaptic quantal events observed at synapses. Small transient inward currents were dependent on extracellular Ca2+ and were abolished by Brilliant Blue G, suggesting they were mediated by P2X7 receptors. Altogether, these results suggest the existence of a positive feedback mechanism mediated by P2X7 receptor-stimulated exocytotic release of ATP that would act on P2X7 receptors on the same or neighbor cells to further stimulate its own release and negatively control N2a cell differentiation. PMID:21292765

  5. System Engineering and Technical Challenges Overcome in the J-2X Rocket Engine Development Project

    NASA Technical Reports Server (NTRS)

    Ballard, Richard O.

    2012-01-01

    Beginning in 2006, NASA initiated the J-2X engine development effort to develop an upper stage propulsion system to enable the achievement of the primary objectives of the Constellation program (CxP): provide continued access to the International Space Station following the retirement of the Space Station and return humans to the moon. The J-2X system requirements identified to accomplish this were very challenging and the time expended over the five years following the beginning of the J- 2X effort have been noteworthy in the development of innovations in both the fields for liquid rocket propulsion and system engineering.

  6. Purinergic P2X7 receptor regulates lung surfactant secretion in a paracrine manner

    PubMed Central

    Mishra, Amarjit; Chintagari, Narendranath Reddy; Guo, Yujie; Weng, Tingting; Su, Lijing; Liu, Lin

    2011-01-01

    Alveolar epithelium is composed of alveolar epithelial cells of type I (AEC I) and type II (AEC II). AEC II secrete lung surfactant by means of exocytosis. P2X7 receptor (P2X7R), a P2 purinergic receptor, has been implicated in the regulation of synaptic transmission and inflammation. Here, we report that P2X7R, which is expressed in AEC I but not AEC II, is a novel mediator for the paracrine regulation of surfactant secretion in AEC II. In primary co-cultures of AEC I and AEC II benzoyl ATP (BzATP; an agonist of P2X7R) increased surfactant secretion, which was blocked by the P2X7R antagonist Brilliant Blue G. This effect was observed in AEC II co-cultured with human embryonic kidney HEK-293 cells stably expressing rat P2X7R, but not when co-cultured with AEC I in which P2X7R was knocked down or in co-cultures of AEC I and AEC II isolated from P2X7R−/− mice. BzATP-mediated secretion involved P2Y2 receptor signaling because it was reduced by the addition of the ATP scavengers apyrase and adenosine deaminase and the P2Y2 receptor antagonist suramin. However, the stimulation with BzATP might also release other substances that potentially increase surfactant secretion as a greater stimulation of secretion was observed in AEC II incubated with BzATP when co-cultured with E10 or HEK-293-P2X7R cells than with ATP alone. P2X7R−/− mice failed to increase surfactant secretion in response to hyperventilation, pointing to the physiological relevance of P2X7R in maintaining surfactant homeostasis in the lung. These results suggest that the activation of P2X7R increases surfactant secretion by releasing ATP from AEC I and subsequently stimulating P2Y2 receptors in AEC II. PMID:21266468

  7. New P2X3 receptor antagonists. Part 2: Identification and SAR of quinazolinones.

    PubMed

    Szántó, Gábor; Makó, Attila; Vágó, István; Hergert, Tamás; Bata, Imre; Farkas, Bence; Kolok, Sándor; Vastag, Mónika

    2016-08-15

    Numerous potent P2X3 antagonists have been discovered and the therapeutic potential of P2X3 antagonism already comprises proof-of-concept data obtained in clinical trials with the most advanced compound. We have lately reported the discovery and optimization of thia-triaza-tricycle compounds with potent P2X3 antagonistic properties. This Letter describes the SAR of a back-up series containing a 4-oxo-quinazoline central ring. The discovery of the highly potent compounds 51 is presented.

  8. Design and performance of 4 x 5120-element visible and 2 x 2560-element shortwave infrared multispectral focal planes

    NASA Technical Reports Server (NTRS)

    Tower, J. R.; Cope, A. D.; Pellon, L. E.; Mccarthy, B. M.; Strong, R. T.

    1986-01-01

    Two solid-state sensors for use in remote sensing instruments operating in the pushbroom mode are examined. The design and characteristics of the visible/near-infrared (VIS/NIR) device and the short-wavelength infrared (SWIR) device are described. The VIS/NIR is a CCD imager with four parallel sensor lines, each 1024 pixel long; the chip design and filter system of the VIS/NIR are studied. The performance of the VIS/NIR sensor with mask and its system performance are measured. The SWIR is a dual-band line imager consisting of palladium silicide Schottky-barrier detectors coupled to CCD multiplexers; the performance of the device is analyzed. The substrate materials and layout designs used to assemble the 4 x 5120-element VIS/NIR array and the 2 x 2560-element SWIR array are discussed, and the planarity of the butted arrays are verified using a profilometer. The optical and electrical characteristics, and the placement and butting accuracy of the arrays are evaluated. It is noted that the arrays met or exceed their expected performance.

  9. Building layered NixCo2x(OH)6x nanosheets decorated three-dimensional Ni frameworks for electrochemical applications

    NASA Astrophysics Data System (ADS)

    Liu, Zhao-Qing; Chen, Gao-Feng; Zhou, Pei-Lin; Li, Nan; Su, Yu-Zhi

    2016-06-01

    To achieve high electrochemical performance in energy storage and conversion devices, transition metal hydroxides electrode materials need enhancing their intrinsic poor conductivity and fully utilizing their unexploited active sites. Accordingly, a simple and effective strategy is developed to synthesize layered NixCo2x(OH)6x nanosheets using dual three-dimensional Ni as structural and conductive support system. Owing to highly electrical conductivity, rich of interconnected ion/electron transport pathways, and robust structure stability, NixCo2x(OH)6x@Ni electrode exhibits remarkably high specific capacitance, excellent rate capability, and superior cycle stability. Moreover, the asymmetric supercapacitor assembled by NixCo2x(OH)6x@Ni and activated carbon/carbon nanotube achieves a large working voltage window of 1.5 V, a high energy density (≈44.2 Wh kg-1 at a power density of 750 W kg-1) and outstanding long-term cycle ability (remaining 100% of the initial Csp after 5000 cycles). Furthermore, the NixCo2x(OH)6x@Ni as an oxygen evolution reaction electrocatalyst shows small onset overpotential (263 mV), low Tafel slope (78 mV dec-1), large anodic current density of 30 mA cm-2 at a low overpotential of 336 mV and prominent electrochemical durability.

  10. Two P2X1 receptor transcripts able to form functional channels are present in most human monocytes.

    PubMed

    López-López, Cintya; Jaramillo-Polanco, Josue; Portales-Pérez, Diana P; Gómez-Coronado, Karen S; Rodríguez-Meléndez, Jessica G; Cortés-García, Juan D; Espinosa-Luna, Rosa; Montaño, Luis M; Barajas-López, Carlos

    2016-12-15

    To characterize the presence and general properties of P2X1 receptors in single human monocytes we used RT-PCR, flow cytometry, and the patch-clamp and the two-electrode voltage-clamp techniques. Most human monocytes expressed the canonical P2X1 (90%) and its splicing variant P2X1del (88%) mRNAs. P2X1 receptor immunoreactivity was also observed in 70% of these cells. Currents mediated by P2X1 (EC50=1.9±0.8µm) and P2X1del (EC50 >1000µm) channels, expressed in Xenopus leavis oocytes, have different ATP sensitivity and kinetics. Both currents mediated by P2X1 and P2X1del channels kept increasing during the continuous presence of high ATP concentrations. Currents mediated by the native P2X1 receptors in human monocytes showed an EC50=6.3±0.2µm. Currents have kinetics that resemble those observed for P2X1 and P2X1del receptors in oocytes. Our study is the first to demonstrate the expression of P2X1 transcript and its splicing variant P2X1del in most human monocytes. We also, for the first time, described functional homomeric P2X1del channels and demonstrated that currents mediated by P2X1 or P2X1del receptors, during heterologous expression, increased in amplitude when activated with high ATP concentrations in a similar fashion to those channels that increase their conductance under similar conditions, such as P2X7, P2X2, and P2X4 channels.

  11. Thermal expansion of Cr{sub 2x}Fe{sub 2-2x}Mo{sub 3}O{sub 12}, Al{sub 2x}Fe{sub 2-2x}Mo{sub 3}O{sub 12} and Al{sub 2x}Cr{sub 2-2x}Mo{sub 3}O{sub 12} solid solutions

    SciTech Connect

    Ari, M.; Jardim, P.M.; Marinkovic, B.A. Rizzo, F.; Ferreira, F.F.

    2008-06-15

    The transition temperature from monoclinic to orthorhombic and the thermal expansion of the orthorhombic phase were investigated for three systems of the family A{sub 2}M{sub 3}O{sub 12}: Cr{sub 2x}Fe{sub 2-2x}Mo{sub 3}O{sub 12}, Al{sub 2x}Fe{sub 2-2x}Mo{sub 3}O{sub 12} and Al{sub 2x}Cr{sub 2-2x}Mo{sub 3}O{sub 12}. It was possible to obtain a single-phase solid solution in all studied samples (x=0, 0.1, 0.3, 0.5, 0.7, 0.9 and 1). A linear relationship between the transition temperature and the fraction of A{sup 3+} cations (x) was observed for each system. In all orthorhombic solid solutions studied here the observed thermal expansion was anisotropic. These anisotropic thermal expansion properties of crystallographic axes a, b and c result in a low positive or near-zero overall linear coefficient of thermal expansion ({alpha}{sub l}={alpha}{sub V}/3). The relationship between the size of A{sup 3+} cations in A{sub 2}M{sub 3}O{sub 12} and the coefficient of thermal expansion is discussed. Near-zero thermal expansion of Cr{sub 2}Mo{sub 3}O{sub 12} is explained by the behavior of Cr-O and Mo-O bond distances, Cr-Mo non-bond distances and Cr-O-Mo bond angles with increasing temperature, estimated by Rietveld analysis of synchrotron X-ray powder diffraction data. - Graphical abstract: In this figure, all published overall linear coefficients of thermal expansion for orthorhombic A{sub 2}M{sub 3}O{sub 12} family obtained through diffraction methods as a function of A{sup 3+} cation radii size, together with dilatometric results, are plotted. Our results indicate that Cr{sub 2}Mo{sub 3}O{sub 12} does not exactly follow the established relationship.

  12. Window type: 2x3 fixed multipaned steel window flanked by 1x3 ...

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

    Window type: 2x3 fixed multipaned steel window flanked by 1x3 multipaned steel casements. Concrete sill and spandrel also illustrated. Building 43, facing east - Harbor Hills Housing Project, 26607 Western Avenue, Lomita, Los Angeles County, CA

  13. Two-dimensional wide-band-gap nitride semiconductors: Single-layer 1 T -X N2 (X =S ,Se , and Te )

    NASA Astrophysics Data System (ADS)

    Lin, Jia-He; Zhang, Hong; Cheng, Xin-Lu; Miyamoto, Yoshiyuki

    2016-11-01

    Recently, the two-dimensional (2D) semiconductors arsenene and antimonene, with band gaps larger than 2.0 eV, have attracted tremendous interest, especially for potential applications in optoelectronic devices with a photoresponse in the blue and UV range. Motivated by this exciting discovery, types of highly stable wide-band-gap 2D nitride semiconductors were theoretically designed. We propose single-layer 1 T -X N2 (X =S , Se, and Te) via first-principles simulations. We compute 1 T -X N2 (X =S , Se, and Te) with indirect band gaps of 2.825, 2.351, and 2.336 eV, respectively. By applying biaxial strain, they are able to induce the transition from a wide-band-gap semiconductor to a metal, and the range of absorption spectra of 1 T -X N2 (X =S , Se, and Te) obviously extend from the ultraviolet region to the blue-purple light region. With an underlying graphene, we find that 1 T -X N2 can completely shield the light absorption of graphene in the range of 1-1.6 eV. Our research paves the way for optoelectronic devices working under blue or UV light, and mechanical sensors based on these 2D crystals.

  14. Radiosensitizing Effect of P2X7 Receptor Antagonist on Melanoma in vitro and in vivo.

    PubMed

    Tanamachi, Keisuke; Nishino, Keisuke; Mori, Natsuki; Suzuki, Toshihiro; Tanuma, Sei-Ichi; Abe, Ryo; Tsukimoto, Mitsutoshi

    2017-03-24

    Melanoma is highly malignant, and generally exhibits radioresistance, responding poorly to radiation therapy. We previously reported that activation of P2X7, P2Y6, and P2Y12 receptors is involved in the DNA damage response after γ-irradiation of human lung adenocarcinoma A549 cells. However, it is not clear whether these receptors are also involved in the case of melanoma cells, although P2X7 receptor is highly expressed in various cancers, including melanoma. Here, we show that P2X7 receptor antagonist enhances radiation-induced cytotoxicity in B16 melanoma cells in vitro and in vivo. We confirmed that these cells express P2X7 receptor mRNA and exhibit P2X7 receptor-mediated activities, such as ATP-induced pore formation and cytotoxicity. We further examined the radiosensitizing effect of P2X7 receptor antagonist Brilliant Blue G (BBG) in vitro by colony formation assay of B16 cells. γ-Irradiation dose-dependently reduced cell survival, and pretreatment with BBG enhanced the radiation-induced cytotoxicity. BBG pretreatment also decreased the number of DNA repair foci in nuclei, supporting involvement of P2X7 receptor in the DNA damage response. Finally, we investigated the radiosensitizing effect of BBG on B16 melanoma cells inoculated into the hind footpad of C57BL/6 mice. Neither 1 Gy γ-irradiation alone nor BBG alone suppressed the increase of tumor volume, but the combination of irradiation and BBG significantly suppressed tumor growth. Our results suggest that P2X7 receptor antagonist BBG has a radiosensitizing effect in melanoma in vitro and in vivo. BBG, which is used as a food coloring agent, appears to be a promising candidate as a radiosensitizer.

  15. The role of P2X7 receptors in a rodent PCP-induced schizophrenia model

    PubMed Central

    Koványi, Bence; Csölle, Cecilia; Calovi, Stefano; Hanuska, Adrienn; Kató, Erzsébet; Köles, László; Bhattacharya, Anindya; Haller, József; Sperlágh, Beáta

    2016-01-01

    P2X7 receptors (P2X7Rs) are ligand-gated ion channels sensitive to extracellular ATP. Here we examined for the first time the role of P2X7R in an animal model of schizophrenia. Using the PCP induced schizophrenia model we show that both genetic deletion and pharmacological inhibition of P2X7Rs alleviate schizophrenia-like behavioral alterations. In P2rx7+/+ mice, PCP induced hyperlocomotion, stereotype behavior, ataxia and social withdrawal. In P2X7 receptor deficient mice (P2rx7−/−), the social interactions were increased, whereas the PCP induced hyperlocomotion and stereotype behavior were alleviated. The selective P2X7 receptor antagonist JNJ-47965567 partly replicated the effect of gene deficiency on PCP-induced behavioral changes and counteracted PCP-induced social withdrawal. We also show that PCP treatment upregulates and increases the functional responsiveness of P2X7Rs in the prefrontal cortex of young adult animals. The amplitude of NMDA evoked currents recorded from layer V pyramidal neurons of cortical slices were slightly decreased by both genetic deletion of P2rx7 and by JNJ-47965567. PCP induced alterations in mRNA expression encoding schizophrenia-related genes, such as NR2A, NR2B, neuregulin 1, NR1 and GABA α1 subunit were absent in the PFC of young adult P2rx7−/− animals. Our findings point to P2X7R as a potential therapeutic target in schizophrenia. PMID:27824163

  16. Porphyromonas gingivalis fimbriae dampen P2X7-dependent IL-1β secretion

    PubMed Central

    Morandini, Ana Carolina; Ramos-Junior, Erivan S.; Potempa, Jan; Nguyen, Ky-Anh; Oliveira, Ana Carolina; Bellio, Maria; Ojcius, David M.; Scharfstein, Julio; Coutinho-Silva, Robson

    2014-01-01

    Porphyromonas gingivalis is a major contributor to the pathogenesis of periodontitis, an infection-driven inflammatory disease that leads to bone destruction. This pathogen stimulates pro-IL-1β synthesis but not mature IL-1β secretion, unless the P2X7 receptor is activated by extracellular ATP. Here, we investigated the role of Pg fimbriae in eATP-induced IL-1β release. Bone marrow derived macrophages (BMDMs) from wild type (WT) or P2X7-deficient mice were infected with Pg (strain 381) or isogenic fimbriae deficient (strain DPG3) with or without subsequent eATP stimulation. DPG3 induced higher IL-1β secretion after eATP stimulation compared to 381 in WT BMDMs, but not in P2X7-deficient cells. This mechanism was dependent of K+ efflux and Ca2+-iPLA2 activity. Accordingly, non-fimbriated Pg failed to inhibit apoptosis via eATP/P2X7-pathway. Furthermore, Pg-driven stimulation of IL-1β was TLR2- and MyD88-dependent, and irrespective of fimbriae expression. Fimbriae-dependent down-modulation of IL-1β was selective, as levels of other cytokines remained unaffected by P2X7 deficiency. Confocal microscopy demonstrated the presence of discrete P2X7 expression in the absence of Pg stimulation which was enhanced by 381-stimulated cells. Notably, DPG3-infected macrophages revealed a distinct pattern of P2X7 receptor expression with a markedly foci formation. Collectively, these data demonstrate that eATP-induced IL-1β secretion is impaired by Pg fimbriae in a P2X7-dependent manner. PMID:24925032

  17. Desensitization properties of P2X3 receptors shaping pain signaling

    PubMed Central

    Giniatullin, Rashid; Nistri, Andrea

    2013-01-01

    ATP-gated P2X3 receptors are mostly expressed by nociceptive sensory neurons and participate in transduction of pain signals. P2X3 receptors show a combination of fast desensitization onset and slow recovery. Moreover, even low nanomolar agonist concentrations unable to evoke a response, can induce desensitization via a phenomenon called “high affinity desensitization.” We have also observed that recovery from desensitization is agonist-specific and can range from seconds to minutes. The recovery process displays unusually high temperature dependence. Likewise, recycling of P2X3 receptors in peri-membrane regions shows unexpectedly large temperature sensitivity. By applying kinetic modeling, we have previously shown that desensitization characteristics of P2X3 receptor are best explained with a cyclic model of receptor operation involving three agonist molecules binding a single receptor and that desensitization is primarily developing from the open receptor state. Mutagenesis experiments suggested that desensitization depends on a certain conformation of the ATP binding pocket and on the structure of the transmembrane domains forming the ion pore. Further molecular determinants of desensitization have been identified by mutating the intracellular N- and C-termini of P2X3 receptor. Unlike other P2X receptors, the P2X3 subtype is facilitated by extracellular calcium that acts via specific sites in the ectodomain neighboring the ATP binding pocket. Thus, substitution of serine275 in this region (called “left flipper”) converts the natural facilitation induced by extracellular calcium to receptor inhibition. Given their strategic location in nociceptive neurons and unique desensitization properties, P2X3 receptors represent an attractive target for development of new analgesic drugs via promotion of desensitization aimed at suppressing chronic pain. PMID:24367291

  18. Critical Evaluation of P2X7 Receptor Antagonists in Selected Seizure Models

    PubMed Central

    Fischer, Wolfgang; Franke, Heike; Krügel, Ute; Müller, Heiko; Dinkel, Klaus; Lord, Brian; Letavic, Michael A.; Henshall, David C.; Engel, Tobias

    2016-01-01

    The ATP-gated P2X7 receptor (P2X7R) is a non-selective cation channel which senses high extracellular ATP concentrations and has been suggested as a target for the treatment of neuroinflammation and neurodegenerative diseases. The use of P2X7R antagonists may therefore be a viable approach for treating CNS pathologies, including epileptic disorders. Recent studies showed anticonvulsant potential of P2X7R antagonists in certain animal models. To extend this work, we tested three CNS-permeable P2X7R blocker (Brilliant Blue G, AFC-5128, JNJ-47965567) and a natural compound derivative (tanshinone IIA sulfonate) in four well-characterized animal seizure models. In the maximal electroshock seizure threshold test and the pentylenetetrazol (PTZ) seizure threshold test in mice, none of the four compounds demonstrated anticonvulsant effects when given alone. Notably, in combination with carbamazepine, both AFC-5128 and JNJ-47965567 increased the threshold in the maximal electroshock seizure test. In the PTZ-kindling model in rats, useful for testing antiepileptogenic activities, Brilliant Blue G and tanshinone exhibited a moderate retarding effect, whereas the potent P2X7R blocker AFC-5128 and JNJ-47965567 showed a significant and long-lasting delay in kindling development. In fully kindled rats, the investigated compounds revealed modest effects to reduce the mean seizure stage. Furthermore, AFC-5128- and JNJ-47965567-treated animals displayed strongly reduced Iba 1 and GFAP immunoreactivity in the hippocampal CA3 region. In summary, our results show that P2X7R antagonists possess no remarkable anticonvulsant effects in the used acute screening tests, but can attenuate chemically-induced kindling. Further studies would be of interest to support the concept that P2X7R signalling plays a crucial role in the pathogenesis of epileptic disorders. PMID:27281030

  19. Potent and long-lasting inhibition of human P2X2 receptors by copper

    PubMed Central

    Punthambaker, Sukanya; Hume, Richard I.

    2013-01-01

    P2X receptors are ion channels gated by ATP. In rodents these channels are modulated by zinc and copper. Zinc is co-released with neurotransmitter at some synapses and can modulate neuronal activity, but the role of copper in the brain is unclear. Rat P2X2 receptors show potentiation by 2–100 µM zinc or copper in the presence of a submaximal concentration of ATP but are inhibited by zinc or copper at concentrations above 100 µM. In contrast, human P2X2 (hP2X2) receptors show no potentiation and are strongly inhibited by zinc over the range of 2–100 µM. The effect of copper on hP2X2 is of interest because there are human brain disorders in which copper concentration is altered. We found that hP2X2 receptors are potently inhibited by copper (IC50 = 40 nM). ATP responsiveness recovered extremely slowly after copper washout, with full recovery requiring over 1 h. ATP binding facilitated copper binding but not unbinding from this inhibitory site. A mutant receptor in which the first six extracellular cysteines were deleted, C(1–6)S, showed normal copper inhibition, however reducing agents dramatically accelerated recovery from copper inhibition in wild type hP2X2 and the C(1–6)S mutant, indicating that the final two disulfide bonds are required to maintain the high affinity copper binding site. Three histidine residues required for normal zinc inhibition were also required for normal copper inhibition. Humans with untreated Wilson’s disease have excess amounts of copper in the brain. The high copper sensitivity of hP2X2 receptors suggests that they are non-functional in these patients. PMID:24067922

  20. P2X7 receptors induce degranulation in human mast cells.

    PubMed

    Wareham, Kathryn J; Seward, Elizabeth P

    2016-06-01

    Mast cells play important roles in host defence against pathogens, as well as being a key effector cell in diseases with an allergic basis such as asthma and an increasing list of other chronic inflammatory conditions. Mast cells initiate immune responses through the release of newly synthesised eicosanoids and the secretion of pre-formed mediators such as histamine which they store in specialised granules. Calcium plays a key role in regulating both the synthesis and secretion of mast-cell-derived mediators, with influx across the membrane, in particular, being necessary for degranulation. This raises the possibility that calcium influx through P2X receptors may lead to antigen-independent secretion of histamine and other granule-derived mediators from human mast cells. Here we show that activation of P2X7 receptors with both ATP and BzATP induces robust calcium rises in human mast cells and triggers their degranulation; both effects are blocked by the P2X7 antagonist AZ11645373, or the removal of calcium from the extracellular medium. Activation of P2X1 receptors with αβmeATP also induces calcium influx in human mast cells, which is significantly reduced by both PPADS and NF 449. P2X1 receptor activation, however, does not trigger degranulation. The results indicate that P2X7 receptors may play a significant role in contributing to the unwanted activation of mast cells in chronic inflammatory conditions where extracellular ATP levels are elevated.

  1. P2X4: an ATP-activated ionotropic receptor cloned from rat brain.

    PubMed Central

    Soto, F; Garcia-Guzman, M; Gomez-Hernandez, J M; Hollmann, M; Karschin, C; Stühmer, W

    1996-01-01

    Extracellular ATP exerts pronounced biological actions in virtually every organ or tissue that has been studied. In the central and peripheral nervous system, ATP acts as a fast excitatory transmitter in certain synaptic pathways [Evans, R.J., Derkach, V. & Surprenant, A. (1992) Nature (London) 357, 503-505; Edwards, F.A., Gigg, A.J. & Colquhoun, D. (1992) Nature (London) 359, 144-147]. Here, we report the cloning and characterization of complementary DNA from rat brain, encoding an additional member (P2X4) of the emerging multigenic family of ligand-gated ATP channels, the P2X receptors. Expression in Xenopus oocytes gives an ATP-activated cation-selective channel that is highly permeable to Ca2+ and whose sensitivity is modulated by extracellular Zn2+. Surprisingly, the current elicited by ATP is almost insensitive to the common P2X antagonist suramin. In situ hybridization reveals the expression of P2X4 mRNA in central nervous system neurons. Northern blot and reverse transcription-PCR (RT-PCR) analysis demonstrate a wide distribution of P2X4 transcripts in various tissues, including blood vessels and leukocytes. This suggests that the P2X4 receptor might mediate not only ATP-dependent synaptic transmission in the central nervous system but also a wide repertoire of biological responses in diverse tissues. Images Fig. 3 Fig. 4 PMID:8622997

  2. Evaluation of adenine as scaffold for the development of novel P2X3 receptor antagonists.

    PubMed

    Lambertucci, Catia; Sundukova, Mayya; Kachare, Dhuldeo D; Panmand, Deepak S; Dal Ben, Diego; Buccioni, Michela; Marucci, Gabriella; Marchenkova, Anna; Thomas, Ajiroghene; Nistri, Andrea; Cristalli, Gloria; Volpini, Rosaria

    2013-07-01

    Ligands that selectively block P2X3 receptors localized on nociceptive sensory fibres may be useful for the treatment of chronic pain conditions including neuropathic pain, migraine, and inflammatory pain. With the aim at exploring the suitability of adenine moiety as a scaffold for the development of antagonists of this receptor, a series of 9-benzyl-2-aminoadenine derivatives were designed and synthesized. These new compounds were functionally evaluated at rat or human P2X3 receptors expressed in human embryonic kidney (HEK) cells and on native P2X3 receptors from mouse trigeminal ganglion sensory neurons using patch clamp recording under voltage clamp configuration. The new molecules behaved as P2X3 antagonists, as they rapidly and reversibly inhibited (IC50 in the low micromolar range) the membrane currents induced via P2X3 receptor activation by the full agonist α,β-methyleneATP. Introduction of a small lipophilic methyl substituent at the 6-amino group enhanced the activity, in comparison to the corresponding unsubstituted derivative, resulting in the 9-(5-iodo-2-isopropyl-4-methoxybenzyl)-N(6)-methyl-9H-purine-2,6-diamine (24), which appears to be a good antagonist on recombinant and native P2X3 receptors with IC50 = 1.74 ± 0.21 μM.

  3. Effects of Ag-Doping on Thermoelectric Properties of Ca(2-x)AgxSi Alloys

    NASA Astrophysics Data System (ADS)

    Duan, Xingkai; Hu, Konggang; Kuang, Jing; Jiang, Yuezhen; Yi, Dengliang

    2016-11-01

    Ca(2-x)AgxSi (0 ≤ x ≤ 0.1) with 47.5% excess of Ca alloys were fabricated by melting in a tantalum tube and hot pressing technique. Phase structures of the samples were studied by means of x-ray diffraction. The electrical conductivity and Seebeck coefficient of Ca(2-x)AgxSi alloys were studied in the temperature range of 300-873 K. The electrical conductivity of the Ag-doped samples increases within the whole test temperature range. All samples show p-type semiconductor behavior. The electrical conductivity decreases with increasing temperature from 300 K to 873 K, which is typically observed for a degenerate semiconductor. Compared with the undoped samples, Ag-doping (x = 0.04-0.1) results in decreases of Seebeck coefficient, especially Ca(2-x)AgxSi with x = 0.1. The thermal conductivity of the doped samples gradually increases with increasing the Ag-doping content. The Ca(2-x)AgxSi with x = 0.02 sample exhibits the lowest thermal conductivity within the whole test temperature range. The ZT values of Ca(2-x)AgxSi with x = 0.02 sample have an enhancement in the temperature range of 300-873 K by contrast with those of the Ca2Si sample. The maximum ZT value is 0.16 at 837 k, which is observed for the Ca(2-x)AgxSi with x = 0.04 sample.

  4. Transcription factor IRF5 drives P2X4R+-reactive microglia gating neuropathic pain

    PubMed Central

    Masuda, Takahiro; Iwamoto, Shosuke; Yoshinaga, Ryohei; Tozaki-Saitoh, Hidetoshi; Nishiyama, Akira; Mak, Tak W.; Tamura, Tomohiko; Tsuda, Makoto; Inoue, Kazuhide

    2014-01-01

    In response to neuronal injury or disease, microglia adopt distinct reactive phenotypes via the expression of different sets of genes. Spinal microglia expressing the purinergic P2X4 receptor (P2X4R) after peripheral nerve injury (PNI) are implicated in neuropathic pain. Here we show that interferon regulatory factor-5 (IRF5), which is induced in spinal microglia after PNI, is responsible for direct transcriptional control of P2X4R. Upon stimulation of microglia by fibronectin, IRF5 induced de novo expression of P2X4R by directly binding to the promoter region of the P2rx4 gene. Mice lacking Irf5 did not upregulate spinal P2X4R after PNI, and also exhibited substantial resistance to pain hypersensitivity. Furthermore, we found that expression of IRF5 in microglia is regulated by IRF8. Thus, an IRF8-IRF5 transcriptional axis may contribute to shifting spinal microglia toward a P2X4R-expressing reactive state after PNI. These results may provide a new target for treating neuropathic pain. PMID:24818655

  5. Human P2X7 receptor activation induces the rapid shedding of CXCL16.

    PubMed

    Pupovac, Aleta; Foster, Christopher M; Sluyter, Ronald

    2013-03-22

    Activation of the purinergic P2X7 receptor by extracellular ATP induces the shedding of cell-surface molecules including the low-affinity IgE receptor, CD23 from leukocytes. CD23 is a known substrate of a disintegrin and metalloprotease (ADAM)10. The aim of the current study was to determine if P2X7 activation induced the shedding of the chemokine CXCL16, an ADAM10 substrate. Using immunolabelling and flow cytometry we demonstrate that human RPMI 8226 multiple myeloma B cells, which have been previously shown to express P2X7, also express CXCL16. Flow cytometric and ELISA measurements of ATP-induced loss of cell-surface CXCL16 showed that ATP treatment of RPMI 8226 cells induced the rapid shedding of CXCL16. Treatment of RPMI 8226 cells with the specific P2X7 antagonists, AZ10606120 and KN-62 impaired ATP-induced CXCL16 shedding by ~86% and ~90% respectively. RT-PCR demonstrated that ADAM10 is expressed in these cells and treatment of cells with the ADAM10 inhibitor, GI254023X, impaired ATP-induced CXCL16 shedding by ~87%. GI254023X also impaired P2X7-induced CD23 shedding by ∼57%. This data indicates that human P2X7 activation induces the rapid shedding of CXCL16 and that this process involves ADAM10.

  6. Allosteric modulation of ATP-gated P2X receptor channels

    PubMed Central

    Coddou, Claudio; Stojilkovic, Stanko S.; Huidobro-Toro, J. Pablo

    2013-01-01

    Seven mammalian purinergic receptor subunits, denoted P2X1 to P2X7, and several spliced forms of these subunits have been cloned. When heterologously expressed, these cDNAs encode ATP-gated non-selective cation channels organized as trimers. All activated receptors produce cell depolarization and promote Ca2+ influx through their pores and indirectly by activating voltage-gated calcium channels. However, the biophysical and pharmacological properties of these receptors differ considerably, and the majority of these subunits are also capable of forming heterotrimers with other members of the P2X receptor family, which confers further different properties. These channels have three ATP binding domains, presumably located between neighboring subunits, and occupancy of at least two binding sites is needed for their activation. In addition to the orthosteric binding sites for ATP, these receptors have additional allosteric sites that modulate the agonist action at receptors, including sites for trace metals, protons, neurosteroids, reactive oxygen species and phosphoinositides. The allosteric regulation of P2X receptors is frequently receptor-specific and could be a useful tool to identify P2X members in native tissues and their roles in signaling. The focus of this review is on common and receptor-specific allosteric modulation of P2X receptors and the molecular base accounting for allosteric binding sites. PMID:21639805

  7. Ependymal cells along the lateral ventricle express functional P2X(7) receptors.

    PubMed

    Genzen, Jonathan R; Platel, Jean-Claude; Rubio, Maria E; Bordey, Angelique

    2009-09-01

    Ependymal cells line the cerebral ventricles and are located in an ideal position to detect central nervous system injury and inflammation. The signaling mechanisms of ependymal cells, however, are poorly understood. As extracellular adenosine 5'-triphosphate is elevated in the context of cellular damage, experiments were conducted to determine whether ependymal cells along the mouse subventricular zone (SVZ) express functional purinergic receptors. Using whole-cell patch clamp recording, widespread expression of P2X(7) receptors was detected on ependymal cells based on their antagonist sensitivity profile and absence of response in P2X(7) (-/-) mice. Immunocytochemistry confirmed the expression of P2X(7) receptors, and electron microscopy demonstrated that P2X(7) receptors are expressed on both cilia and microvilli. Ca(2+) imaging showed that P2X(7) receptors expressed on cilia are indeed functional. As ependymal cells are believed to function as partner cells in the SVZ neurogenic niche, P2X(7) receptors may play a role in neural progenitor response to injury and inflammation.

  8. Discovery of Potent Antiallodynic Agents for Neuropathic Pain Targeting P2X3 Receptors.

    PubMed

    Jung, Young-Hwan; Kim, Yeo Ok; Lin, Hai; Cho, Joong-Heui; Park, Jin-Hee; Lee, So-Deok; Bae, Jinsu; Kang, Koon Mook; Kim, Yoon-Gyoon; Pae, Ae Nim; Ko, Hyojin; Park, Chul-Seung; Yoon, Myung Ha; Kim, Yong-Chul

    2017-04-06

    Antagonism of the P2X3 receptor is one of the potential therapeutic strategies for the management of neuropathic pain because P2X3 receptors are predominantly localized on small to medium diameter C- and Aδ-fiber primary afferent neurons, which are related to the pain-sensing system. In this study, 5-hydroxy pyridine derivatives were designed, synthesized, and evaluated for their in vitro biological activities by two-electrode voltage clamp assay at hP2X3 receptors. Among the novel hP2X3 receptor antagonists, intrathecal treatment of compound 29 showed parallel efficacy with pregabalin (calcium channel modulator) and higher efficacy than AF353 (P2X3 receptor antagonist) in the evaluation of its antiallodynic effects in spinal nerve ligation rats. However, because compound 29 was inactive by intraperitoneal administration in neuropathic pain animal models due to low cell permeability, the corresponding methyl ester analogue, 28, which could be converted to compound 29 in vivo, was investigated as a prodrug concept. Intravenous injection of compound 28 resulted in potent antiallodynic effects, with ED50 values of 2.62 and 2.93 mg/kg in spinal nerve ligation and chemotherapy-induced peripheral neuropathy rats, respectively, indicating that new drug development targeting the P2X3 receptor could be promising for neuropathic pain, a disease with high unmet medical needs.

  9. Oxidation and reduction behaviors of a prototypic MgO-PuO2-x inert matrix fuel

    NASA Astrophysics Data System (ADS)

    Miwa, Shuhei; Osaka, Masahiko

    2017-04-01

    Oxidation and reduction behaviors of prototypic MgO-based inert matrix fuels (IMFs) containing PuO2-x were experimentally investigated by means of thermogravimetry. The oxidation and reduction kinetics of the MgO-PuO2-x specimen were determined. The oxidation and reduction rates of the MgO-PuO2-x were found to be low compared with those of PuO2-x. It is note that the changes in O/Pu ratios of MgO-PuO2-x from stoichiometry were smaller than those of PuO2-x at high oxygen partial pressure.

  10. Structural and magnetic studies of tin doped α-Fe2O3 (α-SnxFe2-xO3) nanoparticles prepared by microwave assisted synthesis

    NASA Astrophysics Data System (ADS)

    K., Bindu; Chowdhury, P.; Ajith K., M.; Nagaraja, H. S.

    2016-05-01

    Hematite (α-Fe2O3) doped with tetravalent ions have potential applications in various fields such as gas sensors, memories, energy storage devices because of their electrical and magnetic properties. Microwave assisted synthesis was used to prepare Tin doped α-Fe2O3 [α-SnxFe2-xO3]. The structural and morphological studies were investigated using X-ray diffraction (XRD) and Scanning electron microscopy (SEM). XRD patterns revealed that α-Fe2O3 and α-SnxFe2-xO3 were having rhombohedral structure. The compositional study was done by Energy dispersive X-ray Spectroscopy (EDS). The magnetic properties were studied by Vibrating Sample Magnetometry (VSM). Results shows that the prepared samples were found to be antiferromagnetic in nature and the results are discussed in detail.

  11. Angle-resolved photoemission studies on bi-layer colossal magnetoresistive oxides lanthanum(2-2x)strontium(1+2x)manganese(2)oxide(7)

    NASA Astrophysics Data System (ADS)

    Sun, Zhe

    In recent years the studies of manganites have flourished initially because of their Colossal Magnetoresistance (CMR) effect. However the scientific community quickly realized that the fundamental physics is abundant, exotic and challenging. Strong correlations of charge, lattice, spin and orbital degrees of freedom have been found to be responsible for many interesting physical phenomena. Of manganites, La2-2xSr 1+2xMn2O 7 has naturally layered crystal structure. The reduced two-dimensional character amplifies fluctuations of electronic, magnetic, and orbital degrees of freedom and interactions of them, which provides good opportunities for an understanding of the rich physics in manganites. In crystals, electrons have intrinsic charge, spin and orbital degrees of freedom, and the electron-phonon interaction has been an active topic for many decades, thus studies of electrons will definitely shed light on important physics in manganites. Angle-resolved photoemission spectroscopy (ARPES) is an ideal probe of electrons, and so by performing ARPES measurements on La2-2 xSr1+2xMn2 O7 we have obtained abundant knowledge of the physics of strong correlations of various degrees of freedom. We have made many new discoveries by exploring the physics in this com-pound. For the first time we resolved bi-layer split band structure of the prototype of bi-layer manganites, which was predicted by theoretical calculations long time ago. We observed minority-spin states in La2-2 xSr1+2xMn 2O7 (x = 0.36--0.39), which gives direct evidence that this system is not a half-metal in this doping iv range. We gave the first direct measurement of electron-phonon coupling strength in manganites and identified the phonon branches to which electrons couple. In addition to band insulator and Mott insulator there is another type of insulator, in which metallic domains and insulating domains coexist and phase separation and percolation effect play important roles in the metal

  12. Proton and hole conductivity of SrY{sub 2-2x}Ca{sub 2x}O{sub 4-{alpha}} in humid air

    SciTech Connect

    Balakireva, V.B.; Gorelov, V.P.

    1995-05-01

    Previously, the authors studied the electrical conductivity of compounds SrR{sub 2}O{sub 4}(R=Y,Ho-Lu) doped with calcium: SrR{sub 1.98}Ca{sub 0.02}O{sub 4-{alpha}}. In the presence of water vapor, high-temperature ionic transport in these materials was found to be associated with proton mobility. Among the compounds studied, the SrY{sub 2}O{sub 4} ceramic showed the highest ionic conductivity. For this reason, the compounds SrY{sub 2-2x}Ca{sub 2x}O{sub 4-{alpha}} (x=0.01-09.1) were selected for further investigation.

  13. Persistent photoinduced modifications in the phase-separated states of L a2 -2 xS r1 +2 xM n2O7

    NASA Astrophysics Data System (ADS)

    Sun, Kai; Sun, Shuaishuai; Li, Xingyuan; Li, Zhongwen; Zhang, Ruixin; Wei, Linlin; Guo, Cong; Zheng, Dingguo; Tian, Huanfang; Yang, Huaixin; Li, Jianqi

    2016-11-01

    Reentrant charge-ordering transition (RCOT) in the bilayered perovskite manganite L a2 -2 xS r1 +2 xM n2O7 can yield observable changes in both the structural and physical properties associated with phase separation. Our recent measurements show that laser illumination can result in persistent modifications of both the resistance and microstructure in the phase-separated (PS) states. Measurements of photoinduced effects on an x =0.6 sample reveal a persistent increase of the resistance by as much as 40%. Low-temperature laser in situ transmission electron microscope observations clearly show that in situ laser irradiation can modify the PS nature and strengthen the charge-ordered state. We attribute these photoinduced phenomena to the optical modulation of the hole concentration in the Mn O2 layers and the alteration of the local Mn orbital configurations in the PS states.

  14. A solid solution series of atacamite type Ni{sub 2x}Mg{sub 2−2x}Cl(OH){sub 3}

    SciTech Connect

    Bette, Sebastian; Dinnebier, Robert E.; Röder, Christian; Freyer, Daniela

    2015-08-15

    For the first time a complete solid solution series Ni{sub 2x}Mg{sub 2−2x}Cl(OH){sub 3} of an atacamite type alkaline main group metal chloride, Mg{sub 2}Cl(OH){sub 3}, and a transition group metal chloride, Ni{sub 2}Cl(OH){sub 3}, was prepared and characterized by chemical and thermal analysis as well as by Raman and IR spectroscopy, and high resolution laboratory X-ray powder diffraction. All members of the solid solution series crystallize in space group Pnam (62). The main building units of these crystal structures are distorted, edge-linked Ni/MgO{sub 4}Cl{sub 2} and Ni/MgO{sub 5}Cl octahedra. The distribution of Ni{sup 2+}- and Mg{sup 2+}-ions among these two metal-sites within the solid solution series is discussed in detail. The crystallization of the solid solution phases occurs via an intermediate solid solution series, (Ni/Mg)Cl{sub 2x}(OH){sub 2−2x}, with variable Cl: OH ratio up to the 1:3 ratio according to the formula Ni{sub 2x}Mg{sub 2−2x} Cl(OH){sub 3}. For one isolated intermediate solid solution member, Ni{sub 0.70}Mg{sub 0.30}Cl{sub 0.58}(OH){sub 1.42}, the formation and crystal structure is presented as well. - Graphical abstract: For the first time a complete solid solution series, Ni{sub 2x}Mg{sub 2−2x} Cl(OH){sub 3}, was synthesized and characterized. Structure solution by revealed that Ni{sup 2+} prefers to occupy the Jahn–Teller-like distorted hole, out of two available cation sites. Substitution of Ni{sup 2+} by Mg{sup 2+} in atacamite type Ni{sub 2}Cl(OH){sub 3} results in systematic band shifts in Raman and IR spectra as well as in systematic changes in thermal properties. The α-polymorphs M{sub 2}Cl(OH){sub 3} with M=Mg{sup 2+}, Ni{sup 2+} and other divalent transition metal ions, as described in literature, were identified as separate compounds. - Highlights: • First synthesis of solid solution series between main and transition metal chloride. • Ni{sup 2+} prefers to occupy Jahn–Teller-like distorted octahedral holes

  15. 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.

  16. Characterization of protoberberine analogs employed as novel human P2X{sub 7} receptor antagonists

    SciTech Connect

    Lee, Ga Eun; Lee, Won-Gil; Lee, Song-Yi; Lee, Cho-Rong; Park, Chul-Seung; Chang, Sunghoe; Park, Sung-Gyoo; Song, Mi-Ryoung; Kim, Yong-Chul

    2011-04-15

    The P2X{sub 7} receptor (P2X{sub 7}R), a member of the ATP-gated ion channel family, is regarded as a promising target for therapy of immune-related diseases including rheumatoid arthritis and chronic pain. A group of novel protoberberine analogs (compounds 3-5), discovered by screening of chemical libraries, was here investigated with respect to their function as P2X{sub 7}R antagonists. Compounds 3-5 non-competitively inhibited BzATP-induced ethidium ion influx into hP2X{sub 7}-expressing HEK293 cells, with IC{sub 50} values of 100-300 nM. This antagonistic action on the channel further confirmed that both BzATP-induced inward currents and Ca{sup 2+} influx were strongly inhibited by compounds 3-5 in patch-clamp and Ca{sup 2+} influx assays. The antagonists also effectively suppressed downstream signaling of P2X{sub 7} receptors including IL-1{beta} release and phosphorylation of ERK1/2 and p38 proteins in hP2X{sub 7}-expressing HEK293 cells or in differentiated human monocytes (THP-1 cells). Moreover, IL-2 secretion from CD3/CD28-stimulated Jurkat T cell was also dramatically inhibited by the antagonist. These results imply that novel protoberberine analogs may modulate P2X{sub 7} receptor-mediated immune responses by allosteric inhibition of the receptor. - Graphical abstract: Display Omitted

  17. Ion access pathway to the transmembrane pore in P2X receptor channels

    PubMed Central

    Robertson, Janice L.; Li, Mufeng; Silberberg, Shai D.

    2011-01-01

    P2X receptors are trimeric cation channels that open in response to the binding of adenosine triphosphate (ATP) to a large extracellular domain. The x-ray structure of the P2X4 receptor from zebrafish (zfP2X4) receptor reveals that the extracellular vestibule above the gate opens to the outside through lateral fenestrations, providing a potential pathway for ions to enter and exit the pore. The extracellular region also contains a void at the central axis, providing a second potential pathway. To investigate the energetics of each potential ion permeation pathway, we calculated the electrostatic free energy by solving the Poisson-Boltzmann equation along each of these pathways in the zfP2X4 crystal structure and a homology model of rat P2X2 (rP2X2). We found that the lateral fenestrations are energetically favorable for monovalent cations even in the closed-state structure, whereas the central pathway presents strong electrostatic barriers that would require structural rearrangements to allow for ion accessibility. To probe ion accessibility along these pathways in the rP2X2 receptor, we investigated the modification of introduced Cys residues by methanethiosulfonate (MTS) reagents and constrained structural changes by introducing disulfide bridges. Our results show that MTS reagents can permeate the lateral fenestrations, and that these become larger after ATP binding. Although relatively small MTS reagents can access residues in one of the vestibules within the central pathway, no reactive positions were identified in the upper region of this pathway, and disulfide bridges that constrain movements in that region do not prevent ion conduction. Collectively, these results suggest that ions access the pore using the lateral fenestrations, and that these breathe as the channel opens. The accessibility of ions to one of the chambers in the central pathway likely serves a regulatory function. PMID:21624948

  18. The planarian P2X homolog in the regulation of asexual reproduction.

    PubMed

    Sakurai, Toshihide; Lee, Hayoung; Kashima, Makoto; Saito, Yumi; Hayashi, Tetsutaro; Kudome-Takamatsu, Tomomi; Nishimura, Osamu; Agata, Kiyokazu; Shibata, Norito

    2012-01-01

    The growth in size of freshwater planarians in response to nutrient intake is limited by the eventual separation of tail and body fragments in a process called fission. The resulting tail fragment regenerates the entire body as an artificially amputated tail fragment would do, and the body fragment regenerates a tail, resulting in two whole planarians. This regenerative ability is supported by pluripotent somatic stem cells, called neoblasts, which are distributed throughout almost the entire body of the planarian. Neoblasts are the only planarian cells with the ability to continuously proliferate and give rise to all types of cells during regeneration, asexual reproduction, homeostasis, and growth. In order to investigate the molecular characteristics of neoblasts, we conducted an extensive search for neoblast-specific genes using the High Coverage Expression Profiling (HiCEP) method, and tested the function of the resulting candidates by RNAi. Disruption of the expression of one candidate gene, DjP2X-A (Dugesia japonica membrane protein P2X homologue), resulted in a unique phenotype. DjP2X-A RNAi leads to an increase of fission events upon feeding. We confirmed by immunohistochemistry that DjP2X-A is a membrane protein, and elucidated its role in regulating neoblast proliferation, thereby explaining its unique phenotype. We found that DjP2X-A decreases the burst of neoblast proliferation that normally occurs after feeding. We also found that DjP2X-A is required for normal proliferation in starved animals. We propose that DjP2X-A modulates stem cell proliferation in response to the nutritional condition.

  19. P2X7 receptor inhibition protects against ischemic acute kidney injury in mice.

    PubMed

    Yan, Yanli; Bai, Jianwen; Zhou, Xiaoxu; Tang, Jinhua; Jiang, Chunming; Tolbert, Evelyn; Bayliss, George; Gong, Rujun; Zhao, Ting C; Zhuang, Shougang

    2015-03-15

    Activation of the purinergic P2X7 receptor (P2X7R) has been associated with the development of experimental nephritis and diabetic and hypertensive nephropathy. However, its role in acute kidney injury (AKI) remains unknown. In this study, we examined the effects of P2X7R inhibition in a murine model of ischemia-reperfusion (I/R)-induced AKI using A438079, a selective inhibitor of P2X7R. At 24 h after I/R, mice developed renal dysfunction and renal tubular damage, which was accompanied by elevated expression of P2X7R. Early administration of A438079 immediately or 6 h after the onset of reperfusion protected against renal dysfunction and attenuated kidney damage whereas delayed administration of A438079 at 24 h after restoration of perfusion had no protective effects. The protective actions of A438079 were associated with inhibition of renal tubule injury and cell death and suppression of renal expression of monocyte chemotactic protein-1 and regulated upon expression normal T cell expressed and secreted (RANTES). Moreover, I/R injury led to an increase in phosphorylation (activation) of extracellular signal-regulated kinases 1/2 in the kidney; treatment with A438079 diminished this response. Collectively, these results indicate that early P2X7R inhibition is effective against renal tubule injury and proinflammatory response after I/R injury and suggest that targeting P2X7R may be a promising therapeutic strategy for treatment of AKI.

  20. Primitive ATP-activated P2X receptors: discovery, function and pharmacology

    PubMed Central

    Fountain, Samuel J.

    2013-01-01

    Adenosine 5-triphosphate (ATP) is omnipresent in biology. It is therefore no surprise that organisms have evolved multifaceted roles for ATP, exploiting its abundance and restriction of passive diffusion across biological membranes. A striking role is the emergence of ATP as a bona fide transmitter molecule, whereby the movement of ATP across membranes serves as a chemical message through a direct ligand-receptor interaction. P2X receptors are ligand-gated ion channels that mediate fast responses to the transmitter ATP in mammalian cells including central and sensory neurons, vascular smooth muscle, endothelium, and leukocytes. Molecular cloning of P2X receptors and our understanding of structure-function relationships has provided sequence information with which to query an exponentially expanding wealth of genome sequence information including protist, early animal and human pathogen genomes. P2X receptors have now been cloned and characterized from a number of simple organisms. Such work has led to surprising new cellular roles for the P2X receptors family and an unusual phylogeny, with organisms such as Drosophila and C. elegans notably lacking P2X receptors despite retaining ionotropic receptors for other common transmitters that are present in mammals. This review will summarize current work on the evolutionary biology of P2X receptors and ATP as a signaling molecule, discuss what can be drawn from such studies when considering the action of ATP in higher animals and plants, and outline how simple organisms may be exploited experimentally to inform P2X receptor function in a wider context. PMID:24367292

  1. Statins and ATP regulate nuclear pAkt via the P2X7 purinergic receptor in epithelial cells

    SciTech Connect

    Mistafa, Oras; Hoegberg, Johan; Stenius, Ulla

    2008-01-04

    Many studies have documented P2X7 receptor functions in cells of mesenchymal origin. P2X7 is also expressed in epithelial cells and its role in these cells remains largely unknown. Our data indicate that P2X7 regulate nuclear pAkt in epithelial cells. We show that low concentration of atorvastatin, a drug inhibiting HMG-CoA reductase and cholesterol metabolism, or the natural agonist extracellular ATP rapidly decreased the level of insulin-induced phosphorylated Akt in the nucleus. This effect was seen within minutes and was inhibited by P2X7 inhibitors. Experiments employing P2X7 siRNA and HEK293 cells heterologously expressing P2X7 and in vivo experiments further supported an involvement of P2X7. These data indicate that extracellular ATP and statins via the P2X7 receptor modulate insulin-induced Akt signaling in epithelial cells.

  2. Mechanism of action of species-selective P2X7 receptor antagonists

    PubMed Central

    Michel, Anton D; Ng, Sin-Wei; Roman, Shilina; Clay, William C; Dean, David K; Walter, Daryl S

    2009-01-01

    Background and purpose: AZ11645373 and N-{2-methyl-5-[(1R, 5S)-9-oxa-3,7-diazabicyclo[3.3.1]non-3-ylcarbonyl]phenyl}-2-tricyclo[3.3.1.13,7]dec-1-ylacetamide hydrochloride (compound-22) are recently described P2X7 receptor antagonists. In this study we have further characterized these compounds to determine their mechanism of action and interaction with other species orthologues. Experimental approach: Antagonist effects at recombinant and chimeric P2X7 receptors were assessed by ethidium accumulation and radioligand-binding studies. Key results: AZ11645373 and compound-22 were confirmed as selective non-competitive antagonists of human or rat P2X7 receptors respectively. Both compounds were weak antagonists of the mouse and guinea-pig P2X7 receptors and, for each compound, their potency estimates at human and dog P2X7 receptors were similar. The potency of compound-22 was moderately temperature-dependent while that of AZ11645373 was not. The antagonist effects of both compounds were slowly reversible and were not prevented by decavanadate, suggesting that they were allosteric antagonists. Indeed, the compounds competed for binding sites labelled by an allosteric radio-labelled P2X7 receptor antagonist. The species selectivity of AZ11645373, but not compound-22, was influenced by the nature of the amino acid at position 95 of the P2X7 receptor. N2-(3,4-difluorophenyl)-N1-[2-methyl-5-(1-piperazinylmethyl)phenyl]glycinamide dihydrochloride, a positive allosteric modulator of the rat receptor, reduced the potency of compound-22 at the rat receptor but had little effect on the actions of AZ11645373. Conclusions: AZ11645373 and compound-22 are allosteric antagonists of human and rat P2X7 receptors respectively. The differential interaction of the two compounds with the receptor suggests there may be more than one allosteric regulatory site on the P2X7 receptor at which antagonists can bind and affect receptor function. PMID:19309360

  3. Photovoltaic device

    DOEpatents

    Reese, Jason A; Keenihan, James R; Gaston, Ryan S; Kauffmann, Keith L; Langmaid, Joseph A; Lopez, Leonardo; Maak, Kevin D; Mills, Michael E; Ramesh, Narayan; Teli, Samar R

    2017-03-21

    The present invention is premised upon an improved photovoltaic device ("PV device"), more particularly to an improved photovoltaic device with a multilayered photovoltaic cell assembly and a body portion joined at an interface region and including an intermediate layer, at least one interconnecting structural member, relieving feature, unique component geometry, or any combination thereof.

  4. Photovoltaic device

    DOEpatents

    Reese, Jason A.; Keenihan, James R.; Gaston, Ryan S.; Kauffmann, Keith L.; Langmaid, Joseph A.; Lopez, Leonardo C.; Maak, Kevin D.; Mills, Michael E.; Ramesh, Narayan; Teli, Samar R.

    2015-06-02

    The present invention is premised upon an improved photovoltaic device ("PV device"), more particularly to an improved photovoltaic device with a multilayered photovoltaic cell assembly and a body portion joined at an interface region and including an intermediate layer, at least one interconnecting structural member, relieving feature, unique component geometry, or any combination thereof.

  5. Photovoltaic device

    DOEpatents

    Reese, Jason A.; Keenihan, James R.; Gaston, Ryan S.; Kauffmann, Keith L.; Langmaid, Joseph A.; Lopez, Leonardo C.; Maak, Kevin D.; Mills, Michael E.; Ramesh, Narayan; Teli, Samar R.

    2015-09-01

    The present invention is premised upon an improved photovoltaic device ("PV device"), more particularly to an improved photovoltaic device (10) with a multilayered photovoltaic cell assembly (100) and a body portion (200) joined at an interface region (410) and including an intermediate layer (500), at least one interconnecting structural member (1500), relieving feature (2500), unique component geometry, or any combination thereof.

  6. P2X7 receptor activation regulates rapid unconventional export of transglutaminase-2

    PubMed Central

    Adamczyk, Magdalena; Griffiths, Rhiannon; Dewitt, Sharon; Knäuper, Vera; Aeschlimann, Daniel

    2015-01-01

    ABSTRACT Transglutaminases (denoted TG or TGM) are externalized from cells via an unknown unconventional secretory pathway. Here, we show for the first time that purinergic signaling regulates active secretion of TG2 (also known as TGM2), an enzyme with a pivotal role in stabilizing extracellular matrices and modulating cell–matrix interactions in tissue repair. Extracellular ATP promotes TG2 secretion by macrophages, and this can be blocked by a selective antagonist against the purinergic receptor P2X7 (P2X7R, also known as P2RX7). Introduction of functional P2X7R into HEK293 cells is sufficient to confer rapid, regulated TG2 export. By employing pharmacological agents, TG2 release could be separated from P2X7R-mediated microvesicle shedding. Neither Ca2+ signaling alone nor membrane depolarization triggered TG2 secretion, which occurred only upon receptor membrane pore formation and without pannexin channel involvement. A gain-of-function mutation in P2X7R associated with autoimmune disease caused enhanced TG2 externalization from cells, and this correlated with increased pore activity. These results provide a mechanistic explanation for a link between active TG2 secretion and inflammatory responses, and aberrant enhanced TG2 activity in certain autoimmune conditions. PMID:26542019

  7. Atomic-scale recognition of surface structure and intercalation mechanism of Ti3C2X.

    PubMed

    Wang, Xuefeng; Shen, Xi; Gao, Yurui; Wang, Zhaoxiang; Yu, Richeng; Chen, Liquan

    2015-02-25

    MXenes represent a large family of functionalized two-dimensional (2D) transition-metal carbides and carbonitrides. However, most of the understanding on their unique structures and applications stops at the theoretical suggestion and lack of experimental support. Herein, the surface structure and intercalation chemistry of Ti3C2X are clarified at the atomic scale by aberration-corrected scanning transmission electron microscope (STEM) and density functional theory (DFT) calculations. The STEM studies show that the functional groups (e.g., OH(-), F(-), O(-)) and the intercalated sodium (Na) ions prefer to stay on the top sites of the centro-Ti atoms and the C atoms of the Ti3C2 monolayer, respectively. Double Na-atomic layers are found within the Ti3C2X interlayer upon extensive Na intercalation via two-phase transition and solid-solution reactions. In addition, aluminum (Al)-ion intercalation leads to horizontal sliding of the Ti3C2X monolayer. On the basis of these observations, the previous monolayer surface model of Ti3C2X is modified. DFT calculations using the new modeling help to understand more about their physical and chemical properties. These findings enrich the understanding of the MXenes and shed light on future material design and applications. Moreover, the Ti3C2X exhibits prominent rate performance and long-term cycling stability as an anode material for Na-ion batteries.

  8. Synthesis and magnetic characterization of Sr-based Ni{sub 2}X-type hexaferrite

    SciTech Connect

    Kamishima, K. Mashiko, T.; Kakizaki, K.; Sakai, M.; Watanabe, K.; Abe, H.

    2015-10-15

    We have investigated the synthesis conditions, and the magnetic properties of the Sr{sub 2}Ni{sub 2}X-type hexagonal ferrite, Sr{sub 2}Ni{sub 2}Fe{sub 28}O{sub 46}. The Sr{sub 2}Ni{sub 2}X-type hexaferrite was synthesized at 1240{sup ∘}C. The spontaneous magnetization at 5 K was 44.2 μ{sub B}/f.u., suggesting that most of the Ni{sup 2+} ions are at the up-spin octahedral sites in the spinel-structure blocks within the model of a Néel-type collinear ferrimagnetic structure. The Curie temperature of the Sr{sub 2}Ni{sub 2}X-type hexaferrite was estimated to be T{sub C}[Sr{sub 2}Ni{sub 2}X] = 472{sup ∘}C. This is consistent with the difference of the block stacking structures of SrM-type, Sr{sub 2}Ni{sub 2}X-type, SrNi{sub 2}W-type, and nickel spinel ferrites.

  9. Expression of purinergic P2X receptor subtypes 1, 2, 3 and 7 in equine laminitis.

    PubMed

    Zamboulis, Danae E; Senior, Mark; Clegg, Peter D; Milner, Peter I

    2013-11-01

    Tissue sensitisation and chronic pain have been described in chronic-active laminitis in the horse, making treatment of such cases difficult. Purinergic P2X receptors are linked to chronic pain and inflammation. The aim of this study was to examine the expression of purinergic P2X receptor subtypes 1, 2, 3 and 7 in the hoof, palmar digital vessels and nerve, dorsal root ganglia and spinal cord in horses with chronic-active laminitis (n=5) compared to non-laminitic horses (n=5). Immunohistochemical analysis was performed on tissue sections using antibodies against P2X receptor subtypes 1-3 and 7. In horses with laminitis, there was a reduction in the thickness of the tunica media layer of the palmar digital vein as a proportion of the whole vessel diameter (0.48±0.05) compared to the non-laminitic group (0.57±0.04; P=0.02). P2X receptor subtype 3 was expressed in the smooth muscle layer (tunica media) of the palmar digital artery of horses with laminitis, but was absent in horses without laminitis. There was strong expression of P2X receptor subtype 7 in the proliferating, partially keratinised, epidermal cells of the secondary epidermal lamellae in the hooves of horses with laminitis, but no immunopositivity in horses without laminitis.

  10. The J-2X Fuel Turbopump - Turbine Nozzle Low Cycle Fatigue Acceptance Rationale

    NASA Technical Reports Server (NTRS)

    Hawkins, Lakiesha V.; Duke, Gregory C.; Newman, Wesley R.; Reynolds, David C.

    2011-01-01

    The J-2X Fuel Turbopump (FTP) turbine, which drives the pump that feeds hydrogen to the J-2X engine for main combustion, is based on the J-2S design developed in the early 1970 s. Updated materials and manufacturing processes have been incorporated to meet current requirements. This paper addresses an analytical concern that the J-2X Fuel Turbine Nozzle Low Cycle Fatigue (LCF) analysis did not meet safety factor requirements per program structural assessment criteria. High strains in the nozzle airfoil during engine transients were predicted to be caused by thermally induced stresses between the vane hub, vane shroud, and airfoil. The heritage J-2 nozzle was of a similar design and experienced cracks in the same area where analysis predicted cracks in the J-2X design. Redesign options that did not significantly impact the overall turbine configuration were unsuccessful. An approach using component tests and displacement controlled fracture mechanics analysis to evaluate LCF crack initiation and growth rate was developed. The results of this testing and analysis were used to define the level of inspection on development engine test units. The programmatic impact of developing crack initiation/growth rate/arrest data was significant for the J-2X program. Final Design Certification Review acceptance logic will ultimately be developed utilizing this test and analytical data.

  11. The crystal structure and magnetic properties of Ba2-xSrxCo2Fe12O22

    NASA Astrophysics Data System (ADS)

    Cho, Kwang Lae; Rhee, Chan Hyuk; Kim, Chul Sung

    2014-05-01

    We have synthesized the Ba2-xSrxCo2Fe12O22 samples (x = 0.1, 0.2, 0.3, 0.4, 0.5) by the solid-state reaction method and investigated their crystalline and magnetic properties by X-ray diffractometer (XRD), Mössbauer spectrometer, vibrating sample magnetometer, and network analyzer. XRD patterns show that all samples are rhombohedral with space group R-3m. The lattice constants a0 and c0 decrease with Sr substitution due to smaller ion radius of Sr2+ (1.27 Å) than that of Ba2+ (1.43 Å). The Mössbauer spectroscopy measurements show that the relative area ratios of Fe ion were maintained constant regardless of the Sr concentration. However, average magnetic hyperfine field slightly increased with the Sr concentration. This observation agrees with the fact that the saturation magnetization (Ms) linearly increases due to the increasing super-exchange interaction, originated from the difference in the ionic radius between Ba2+ and Sr2+. To investigate its properties at high frequency range, all samples were sintered at 1100 °C, and complex permeability and permittivity were measured by network analyzer between 100 MHz and 4 GHz. For x below 0.3, the initial permeability at 100 MHz increases, at higher values of x, its value decreases. Our study shows that magnetic properties of Sr2+ substitution for Ba2+ in Y-type hexaferrite as well as low magnetic loss less than 0.1 in 1 GHz band, indicating the potential application of Ba2-xSrxCo2Fe12O22 samples for RF and antenna devices in ultra high frequency band.

  12. Future NTP Development Synergy Leveraged from Current J-2X Engine Development

    NASA Technical Reports Server (NTRS)

    Ballard, Richard O.

    2008-01-01

    This paper is a discussion of how the many long-lead development elements required for the realization of a future nuclear thermal propulsion (NTP) system can be effectively leveraged from the ongoing work being conducted on the J-2X engine program for the Constellation Program. Development studies conducted to date for NTP forward planning have identified a number of technical areas that will require advancement to acceptable technology readiness levels (TRLs) before they can be utilized in NTP system development. These include high-temperature, high-area ratio nozzle extension; long-life, low-NPSP. turbomachinery; and low-boiloff propellant management; and a qualified nuclear fuel element. The current J-2X program is working many of these areas that can be leveraged to support NTP development in a highly compatible and synergistic fashion. In addition to supporting technical development, there are other programmatic issues being worked in the J-2X program that can be leveraged by a future NTP development program. These include compliance with recently-evolved space system requirements such as human-rating, fault tolerance and fracture control. These and other similar mandatory system requirements have been adopted by NASA and can result in a significant technical impact beyond elevation of the root technologies required by NTP. Finally, the exploitation of experience, methodologies, and procedures developed by the J-2X program in the areas of verification, qualification, certification, altitude simulation testing, and facility definition will be especially applicable to a future NTP system. The similarities in system mission (in-space propulsion) and operational environment (vacuum, zero-gee) between J-2X and NTP make this highly synergistic. Thus, it can be $hown that the collective benefit of leveraging experience and technologies developed during the J-2X program can result in significant savings in development cost and schedule for NTP.

  13. Purinergic P2X receptors: structural models and analysis of ligand-target interaction.

    PubMed

    Dal Ben, Diego; Buccioni, Michela; Lambertucci, Catia; Marucci, Gabriella; Thomas, Ajiroghene; Volpini, Rosaria

    2015-01-07

    The purinergic P2X receptors are ligand-gated cation channels activated by the endogenous ligand ATP. They assemble as homo- or heterotrimers from seven cloned subtypes (P2X1-7) and all trimer subunits present a common topology consisting in intracellular N- and C- termini, two transmembrane domains and a large extracellular domain. These membrane proteins are present in virtually all mammalian tissues and regulate a large variety of responses in physio- and pathological conditions. The development of ligands that selectively activate or block specific P2X receptor subtypes hence represents a promising strategy to obtain novel pharmacological tools for the treatment of pain, cancer, inflammation, and neurological, cardiovascular, and endocrine diseases. The publication of the crystal structures of zebrafish P2X4 receptor in inactive and ATP-bound active forms provided structural data for the analysis of the receptor structure, the interpretation of mutagenesis data, and the depiction of ligand binding and receptor activation mechanism. In addition, the availability of ATP-competitive ligands presenting selectivity for P2X receptor subtypes supports the design of new potent and selective ligands with possibly improved pharmacokinetic profiles, with the final aim to obtain new drugs. This study describes molecular modelling studies performed to develop structural models of the human and rat P2X receptors in inactive and active states. These models allowed to analyse the role of some non-conserved residues at ATP binding site and to study the receptor interaction with some non-specific or subtype selective agonists and antagonists.

  14. The P2X7 Receptor Supports Both Life and Death in Fibrogenic Pancreatic Stellate Cells

    PubMed Central

    Haanes, Kristian A.; Schwab, Albrecht; Novak, Ivana

    2012-01-01

    The pancreatic stellate cells (PSCs) have complex roles in pancreas, including tissue repair and fibrosis. PSCs surround ATP releasing exocrine cells, but little is known about purinergic receptors and their function in PSCs. Our aim was to resolve whether PSCs express the multifunctional P2X7 receptor and elucidate how it regulates PSC viability. The number of PSCs isolated from wild type (WT) mice was 50% higher than those from the Pfizer P2X7 receptor knock out (KO) mice. The P2X7 receptor protein and mRNA of all known isoforms were expressed in WT PSCs, while KO PSCs only expressed truncated versions of the receptor. In culture, the proliferation rate of the KO PSCs was significantly lower. Inclusion of apyrase reduced the proliferation rate in both WT and KO PSCs, indicating importance of endogenous ATP. Exogenous ATP had a two-sided effect. Proliferation of both WT and KO cells was stimulated with ATP in a concentration-dependent manner with a maximum effect at 100 µM. At high ATP concentration (5 mM), WT PSCs, but not the KO PSCs died. The intracellular Ca2+ signals and proliferation rate induced by micromolar ATP concentrations were inhibited by the allosteric P2X7 receptor inhibitor az10606120. The P2X7 receptor-pore inhibitor A438079 partially prevented cell death induced by millimolar ATP concentrations. This study shows that ATP and P2X7 receptors are important regulators of PSC proliferation and death, and therefore might be potential targets for treatments of pancreatic fibrosis and cancer. PMID:23284663

  15. Component Testing of the J-2X Augmented Spark Igniter (ASI)

    NASA Technical Reports Server (NTRS)

    Osborne, Robin J.; Peters, Warren T.; Gaspar, Kenny C.; Hauger, Katherine; Kwapisz, Mike J.

    2013-01-01

    In support of the development of the J-2X engine, 201 low pressure, liquid oxygen / liquid hydrogen (LOX/LH2) J-2X Augmented Spark Igniter (ASI) subsystem ignition tests were conducted at Marshall Space Flight Center (MSFC). The main objective of these tests was to start the ASI within the anticipated J-2X engine start box, as well as outside of it, to check for ignition margin. The setup for the J-2X ASI component testing simulated, as much as possible, the tank-head start-up configuration of the ASI within the J-2X Engine. The ignition tests were divided into 124 vacuum start tests to simulate altitude start on a flight engine, and 77 sea-level start tests to simulate the first set of ground tests for the J-2X Engine at Stennis Space Center (SSC). Other ignition parameters that were varied included propellant tank pressures, oxidizer temperature entering the ASI oxidizer feedline, oxidizer valve timing, spark igniter condition (new versus damaged), and oxidizer and fuel feedline orifice sizes. Propellant blowdowns using venturis sized to simulate the ASI resistance allowed calculation of transient propellant mass flow rates as well as global mixture ratio for all ignition tests. Global mixture ratio within the ASI at the time of ignition varied from 0.2 to 1.2. Detailed electronics data obtained from an instrumented ignition lead allowed characterization of the breakdown voltage, sustaining voltage and energy contained in each spark as the ASI propellants ignited. Results indicated that ignition always occurred within the first five sparks when both propellants were present in the ASI chamber.

  16. P2X1 receptor blockade inhibits whole kidney autoregulation of renal blood flow in vivo

    PubMed Central

    Osmond, David A.

    2010-01-01

    In vitro experiments demonstrate that P2X1 receptor activation is important for normal afferent arteriolar autoregulatory behavior, but direct in vivo evidence for this relationship occurring in the whole kidney is unavailable. Experiments were performed to test the hypothesis that P2X1 receptors are important for autoregulation of whole kidney blood flow. Renal blood flow (RBF) was measured in anesthetized male Sprague-Dawley rats before and during P2 receptor blockade with PPADS, P2X1 receptor blockade with IP5I, or A1 receptor blockade with DPCPX. Both P2X1 and A1 receptor stimulation with α,β-methylene ATP and CPA, respectively, caused dose-dependent decreases in RBF. Administration of either PPADS or IP5I significantly blocked P2X1 receptor stimulation. Likewise, administration of DPCPX significantly blocked A1 receptor activation to CPA. Autoregulatory behavior was assessed by measuring RBF responses to reductions in renal perfusion pressure. In vehicle-infused rats, as pressure was decreased from 120 to 100 mmHg, there was no decrease in RBF. However, in either PPADS- or IP5I-infused rats, each decrease in pressure resulted in a significant decrease in RBF, demonstrating loss of autoregulatory ability. In DPCPX-infused rats, reductions in pressure did not cause significant reductions in RBF over the pressure range of 100–120 mmHg, but the autoregulatory curve tended to be steeper than vehicle-infused rats over the range of 80–100 mmHg, suggesting that A1 receptors may influence RBF at lower pressures. These findings are consistent with in vitro data from afferent arterioles and support the hypothesis that P2X1 receptor activation is important for whole kidney autoregulation in vivo. PMID:20335318

  17. P2X7 Receptor Modulates Inflammatory and Functional Pulmonary Changes Induced by Silica

    PubMed Central

    Santana, Patrícia T.; Vieira, Flávia S.; da Graça, Carolyne Lalucha A. L.; Marques-da-Silva, Camila; Machado, Mariana N.; Caruso-Neves, Celso; Zin, Walter A.; Borojevic, Radovan; Coutinho-Silva, Robson

    2014-01-01

    Silicosis is an occupational lung disease, characterized by irreversible and progressive fibrosis. Silica exposure leads to intense lung inflammation, reactive oxygen production, and extracellular ATP (eATP) release by macrophages. The P2X7 purinergic receptor is thought to be an important immunomodulator that responds to eATP in sites of inflammation and tissue damage. The present study investigates the role of P2X7 receptor in a murine model of silicosis. To that end wild-type (C57BL/6) and P2X7 receptor knockout mice received intratracheal injection of saline or silica particles. After 14 days, changes in lung mechanics were determined by the end-inflation occlusion method. Bronchoalveolar lavage and flow cytometry analyzes were performed. Lungs were harvested for histological and immunochemistry analysis of fibers content, inflammatory infiltration, apoptosis, as well as cytokine and oxidative stress expression. Silica particle effects on lung alveolar macrophages and fibroblasts were also evaluated in cell line cultures. Phagocytosis assay was performed in peritoneal macrophages. Silica exposure increased lung mechanical parameters in wild-type but not in P2X7 knockout mice. Inflammatory cell infiltration and collagen deposition in lung parenchyma, apoptosis, TGF-β and NF-κB activation, as well as nitric oxide, reactive oxygen species (ROS) and IL-1β secretion were higher in wild-type than knockout silica-exposed mice. In vitro studies suggested that P2X7 receptor participates in silica particle phagocytosis, IL-1β secretion, as well as reactive oxygen species and nitric oxide production. In conclusion, our data showed a significant role for P2X7 receptor in silica-induced lung changes, modulating lung inflammatory, fibrotic, and functional changes. PMID:25310682

  18. Future NTP Development Synergy Leveraged from Current J-2X Engine Development

    SciTech Connect

    Ballard, Richard O.

    2008-01-21

    This paper is a discussion of how the many long-lead development elements required for the realization of a future nuclear thermal propulsion (NTP) system can be effectively leveraged from the ongoing work being conducted on the J-2X engine program for the Constellation Program. Development studies conducted to date for NTP forward planning have identified a number of technical areas that will require advancement to acceptable technology readiness levels (TRLs) before they can be utilized in NTP system development. These include high-temperature, high-area ratio nozzle extension; long-life, low-NPSP turbomachinery; and low-boiloff propellant management, and a qualified nuclear fuel element. The current J-2X program is working many of these areas that can be leveraged to support NTP development in a highly compatible and synergistic fashion. In addition to supporting technical development, there are other programmatic issues being worked in the J-2X program that can be leveraged by a future NTP development program. These include compliance with recently-evolved space system requirements such as human-rating, fault tolerance and fracture control. These and other similar mandatory system requirements have been adopted by NASA and can result in a significant technical impact beyond elevation of the root technologies required by NTP. Finally, the exploitation of experience, methodologies, and procedures developed by the J-2X program in the areas of verification, qualification, certification, altitude simulation testing, and facility definition will be especially applicable to a future NTP system. The similarities in system mission (in-space propulsion) and operational environment (vacuum, zero-gee) between J-2X and NTP make this highly synergistic. Thus, it can be shown that the collective benefit of leveraging experience and technologies developed during the J-2X program can result in significant savings in development cost and schedule for NTP.

  19. Future NTP Development Synergy Leveraged from Current J-2X Engine Development

    NASA Astrophysics Data System (ADS)

    Ballard, Richard O.

    2008-01-01

    This paper is a discussion of how the many long-lead development elements required for the realization of a future nuclear thermal propulsion (NTP) system can be effectively leveraged from the ongoing work being conducted on the J-2X engine program for the Constellation Program. Development studies conducted to date for NTP forward planning have identified a number of technical areas that will require advancement to acceptable technology readiness levels (TRLs) before they can be utilized in NTP system development. These include high-temperature, high-area ratio nozzle extension; long-life, low-NPSP turbomachinery; and low-boiloff propellant management, and a qualified nuclear fuel element. The current J-2X program is working many of these areas that can be leveraged to support NTP development in a highly compatible and synergistic fashion. In addition to supporting technical development, there are other programmatic issues being worked in the J-2X program that can be leveraged by a future NTP development program. These include compliance with recently-evolved space system requirements such as human-rating, fault tolerance and fracture control. These and other similar mandatory system requirements have been adopted by NASA and can result in a significant technical impact beyond elevation of the root technologies required by NTP. Finally, the exploitation of experience, methodologies, and procedures developed by the J-2X program in the areas of verification, qualification, certification, altitude simulation testing, and facility definition will be especially applicable to a future NTP system. The similarities in system mission (in-space propulsion) and operational environment (vacuum, zero-gee) between J-2X and NTP make this highly synergistic. Thus, it can be shown that the collective benefit of leveraging experience and technologies developed during the J-2X program can result in significant savings in development cost and schedule for NTP.

  20. The role of P2X3 receptors in bilateral masseter muscle allodynia in rats

    PubMed Central

    Tariba Knežević, Petra; Vukman, Robert; Antonić, Robert; Kovač, Zoran; Uhač, Ivone; Simonić-Kocijan, Sunčana

    2016-01-01

    Aim To determine the relationship between bilateral allodynia induced by masseter muscle inflammation and P2X3 receptor expression changes in trigeminal ganglia (TRG) and the influence of intramasseteric P2X3 antagonist administration on bilateral masseter allodynia. Methods To induce bilateral allodynia, rats received a unilateral injection of complete Freund’s adjuvant (CFA) into the masseter muscle. Bilateral head withdrawal threshold (HWT) was measured 4 days later. Behavioral measurements were followed by bilateral masseter muscle and TRG dissection. Masseter tissue was evaluated histopathologically and TRG tissue was analyzed for P2X3 receptor mRNA expression by using quantitative real-time polymerase chain reaction (PCR) analysis. To assess the P2X3 receptor involvement in nocifensive behavior, two doses (6 and 60 μg/50 μL) of selective P2X3 antagonist A-317491 were administrated into the inflamed masseter muscle 4 days after the CFA injection. Bilateral HWT was measured at 15-, 30-, 60-, and 120-minute time points after A-317491 administration. Results HWT was bilaterally reduced after the CFA injection (P < 0.001). Intramasseteric inflammation was confirmed ipsilaterally to the CFA injection. Quantitative real-time PCR analysis demonstrated enhanced P2X3 expression in TRG ipsilaterally to CFA administration (P < 0.01). In comparison with controls, the dose of 6 μg of A-317491 significantly increased bilateral HWT at 15-, 30-, and 60-minute time points after the A-317491 administration (P < 0.001), whereas the dose of 60 μg of A-317491 was efficient at all time points ipsilaterally (P = 0.004) and at 15-, 30-, and 60-minute time points contralaterally (P < 0.001). Conclusion Unilateral masseter inflammation can induce bilateral allodynia in rats. The study provided evidence that P2X3 receptors can functionally influence masseter muscle allodynia and suggested that P2X3 receptors expressed in TRG neurons are involved in masseter

  1. P2X antagonists inhibit styryl dye entry into hair cells.

    PubMed

    Crumling, M A; Tong, M; Aschenbach, K L; Liu, L Qian; Pipitone, C M; Duncan, R K

    2009-07-21

    The styryl pyridinium dyes, FM1-43 and AM1-43, are fluorescent molecules that can permeate the mechanotransduction channels of hair cells, the sensory receptors of the inner ear. When these dyes are applied to hair cells, they enter the cytoplasm rapidly, resulting in a readily detectable intracellular fluorescence that is often used as a molecular indication of mechanotransduction channel activity. However, such dyes can also permeate the ATP receptor, P2X(2). Therefore, we explored the contribution of P2X receptors to the loading of hair cells with AM1-43. The chick inner ear was found to express P2X receptors and to release ATP, similar to the inner ear of mammals, allowing for the endogenous stimulation of P2X receptors. The involvement of these receptors was evaluated pharmacologically, by exposing the sensory epithelium of the chick inner ear to 5 microM AM1-43 under different experimental conditions and measuring the fluorescence in hair cells after fixation of the tissue. Pre-exposure of the tissue to 5 mM EGTA for 15 min, which should eliminate most of the gating "tip links" of the mechanotransduction channels, deceased fluorescence by only 44%. In contrast, P2X receptor antagonists (pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid [PPADS], suramin, 2',3'-O-(2,4,6-trinitrophenyl) ATP [TNP-ATP], and d-tubocurarine) had greater effects on dye loading. PPADS, suramin, and TNP-ATP all decreased intracellular AM1-43 fluorescence in hair cells by at least 69% when applied at a concentration of 100 microM. The difference between d-tubocurarine-treated and control fluorescence was statistically insignificant when d-tubocurarine was applied at a concentration that blocks the mechanotransduction channel (200 microM). At a concentration that also blocks P2X(2) receptors (2 mM), d-tubocurarine decreased dye loading by 72%. From these experiments, it appears that AM1-43 can enter hair cells through endogenously activated P2X receptors. Thus, the contribution of P2X

  2. Planning for Plume Diagnostics for Ground Testing of J-2X Engines at the SSC

    NASA Technical Reports Server (NTRS)

    SaintCyr, William W.; Tejwani, Gopal D.; McVay, Gregory P.; Langford, Lester A.; SaintCyr, William W.

    2010-01-01

    John C. Stennis Space Center (SSC) is the premier test facility for liquid rocket engine development and certification for the National Aeronautics and Space Administration (NASA). Therefore, it is no surprise that the SSC will play the most prominent role in the engine development testing and certification for the J-2X engine. The Pratt & Whitney Rocketdyne J-2X engine has been selected by the Constellation Program to power the Ares I Upper Stage Element and the Ares V Earth Departure Stage in NASA s strategy of risk mitigation for hardware development by building on the Apollo program and other lessons learned to deliver a human-rated engine that is on an aggressive development schedule, with first demonstration flight in 2010 and human test flights in 2012. Accordingly, J-2X engine design, development, test, and evaluation is to build upon heritage hardware and apply valuable experience gained from past development and testing efforts. In order to leverage SSC s successful and innovative expertise in the plume diagnostics for the space shuttle main engine (SSME) health monitoring,1-10 this paper will present a blueprint for plume diagnostics for various proposed ground testing activities for J-2X at SSC. Complete description of the SSC s test facilities, supporting infrastructure, and test facilities is available in Ref. 11. The A-1 Test Stand is currently being prepared for testing the J-2X engine at sea level conditions. The A-2 Test Stand is currently being used for testing the SSME and may also be used for testing the J-2X engine at sea level conditions in the future. Very recently, ground-breaking ceremony for the new A-3 rocket engine test stand took place at SSC on August 23, 2007. A-3 is the first large - scale test stand to be built at the SSC since the A and B stands were constructed in the 1960s. The A-3 Test Stand will be used for testing J-2X engines under vacuum conditions simulating high altitude operation at approximately 30,480 m (100,000 ft

  3. P2X7 receptors at adult neural progenitor cells of the mouse subventricular zone.

    PubMed

    Messemer, Nanette; Kunert, Christin; Grohmann, Marcus; Sobottka, Helga; Nieber, Karen; Zimmermann, Herbert; Franke, Heike; Nörenberg, Wolfgang; Straub, Isabelle; Schaefer, Michael; Riedel, Thomas; Illes, Peter; Rubini, Patrizia

    2013-10-01

    Neurogenesis requires the balance between the proliferation of newly formed progenitor cells and subsequent death of surplus cells. RT-PCR and immunocytochemistry demonstrated the presence of P2X7 receptor mRNA and immunoreactivity in cultured neural progenitor cells (NPCs) prepared from the adult mouse subventricular zone (SVZ). Whole-cell patch-clamp recordings showed a marked potentiation of the inward current responses both to ATP and the prototypic P2X7 receptor agonist dibenzoyl-ATP (Bz-ATP) at low Ca(2+) and zero Mg(2+) concentrations in the bath medium. The Bz-ATP-induced currents reversed their polarity near 0 mV; in NPCs prepared from P2X7(-/-) mice, Bz-ATP failed to elicit membrane currents. The general P2X/P2Y receptor antagonist PPADS and the P2X7 selective antagonists Brilliant Blue G and A-438079 strongly depressed the effect of Bz-ATP. Long-lasting application of Bz-ATP induced an initial current, which slowly increased to a steady-state response. In combination with the determination of YO-PRO uptake, these experiments suggest the dilation of a receptor-channel and/or the recruitment of a dye-uptake pathway. Ca(2+)-imaging by means of Fura-2 revealed that in a Mg(2+)-deficient bath medium Bz-ATP causes [Ca(2+)](i) transients fully depending on the presence of external Ca(2+). The MTT test indicated a concentration-dependent decrease in cell viability by Bz-ATP treatment. Correspondingly, Bz-ATP led to an increase in active caspase 3 immunoreactivity, indicating a P2X7-controlled apoptosis. In acute SVZ brain slices of transgenic Tg(nestin/EGFP) mice, patch-clamp recordings identified P2X7 receptors at NPCs with pharmacological properties identical to those of their cultured counterparts. We suggest that the apoptotic/necrotic P2X7 receptors at NPCs may be of particular relevance during pathological conditions which lead to increased ATP release and thus could counterbalance the ensuing excessive cell proliferation.

  4. Crystal structure, phase transition and conductivity study of two new organic - inorganic hybrids: [(CH2)7(NH3)2]X2, X = Cl/Br

    NASA Astrophysics Data System (ADS)

    Mostafa, Mohga Farid; El-khiyami, Shimaa Said; Abd-Elal, Seham Kamal

    2017-01-01

    Two hybrids 1,7-heptanediammonium di-halide, [(C7H20N2]X2,X = Cl/Br crystallize in monoclinic P21/c, Z = 4. [(C7H20N2]Cl2: a = 4.7838 (2) Å, b = 16.9879 (8) Å, c = 13.9476 (8) Å, β = 97.773 (2)°, V = 1203.58(10) Å3, D = 1.137 g/cm3, λ = 0.71073 Å, R = 0.052 for 1055 reflections with I > 2σ(I), T = 298(2) K. [(C7H20N2]Br2: a = 4.7952 (10) Å, b = 16.9740 (5) Å, c = 13.9281 (5) Å, β = 97.793 (2)°, V = 1203.83(6) Å3, D = 1.612 g/cm3, λ = 0.71073 Å, R = 0.03 for 1959 reflections with I > 2σ(I) T = 298(2) K. Asymmetric unit cell of [(C7H20N2]X2,X = Cl/Br, each consist of one heptane-1,7-diammonium cation and two halide anions. The organic hydrocarbon layers pack in a stacked herring-bone manner, hydrogen bonded to the halide ions. Lattice potential energy is 1568.59 kJ/mol and 1560.78 kJ/mol, and cation molar volumes are 0.295 nm3 and 0.300 nm3 for chloride and bromide respectively. DTA confirmed chain melting transitions for both hybrids below T ∼ 340 K. Dielectric and ac conductivity measurements (290 < T K < 410; 0.080 < f kHz<100) indicated higher conductivity and activation energy of bromide for T > 340 K. Cross over from Jonscher's universal dielectric response at low temperatures T < 340 K to super-linear power law for T > 340 K is observed. At high temperatures halide ion hopping in accordance with the jump relaxation model prevails.

  5. Distribution of purinergic P2X receptors in the equine digit, cervical spinal cord and dorsal root ganglia.

    PubMed

    Zamboulis, D E; Senior, J M; Clegg, P D; Gallagher, J A; Carter, S D; Milner, P I

    2013-09-01

    Purinergic pathways are considered important in pain transmission, and P2X receptors are a key part of this system which has received little attention in the horse. The aim of this study was to identify and characterise the distribution of P2X receptor subtypes in the equine digit and associated vasculature and nervous tissue, including peripheral nerves, dorsal root ganglia and cervical spinal cord, using PCR, Western blot analysis and immunohistochemistry. mRNA signal for most of the tested P2X receptor subunits (P2X1-5, 7) was detected in all sampled equine tissues, whereas P2X6 receptor subunit was predominantly expressed in the dorsal root ganglia and spinal cord. Western blot analysis validated the specificity of P2X1-3, 7 antibodies, and these were used in immunohistochemistry studies. P2X1-3, 7 receptor subunits were found in smooth muscle cells in the palmar digital artery and vein with the exception of the P2X3 subunit that was present only in the vein. However, endothelial cells in the palmar digital artery and vein were positive only for P2X2 and P2X3 receptor subunits. Neurons and nerve fibres in the peripheral and central nervous system were positive for P2X1-3 receptor subunits, whereas glial cells were positive for P2X7 and P2X1 and 2 receptor subunits. This previously unreported distribution of P2X subtypes may suggest important tissue specific roles in physiological and pathological processes.

  6. Microfluidic Device

    NASA Technical Reports Server (NTRS)

    Tai, Yu-Chong (Inventor); Zheng, Siyang (Inventor); Lin, Jeffrey Chun-Hui (Inventor); Kasdan, Harvey L. (Inventor)

    2017-01-01

    Described herein are particular embodiments relating to a microfluidic device that may be utilized for cell sensing, counting, and/or sorting. Particular aspects relate to a microfabricated device that is capable of differentiating single cell types from dense cell populations. One particular embodiment relates a device and methods of using the same for sensing, counting, and/or sorting leukocytes from whole, undiluted blood samples.

  7. Microfluidic Device

    NASA Technical Reports Server (NTRS)

    Tai, Yu-Chong (Inventor); Zheng, Siyang (Inventor); Lin, Jeffrey Chun-Hui (Inventor); Kasdan, Harvey (Inventor)

    2015-01-01

    Described herein are particular embodiments relating to a microfluidic device that may be utilized for cell sensing, counting, and/or sorting. Particular aspects relate to a microfabricated device that is capable of differentiating single cell types from dense cell populations. One particular embodiment relates a device and methods of using the same for sensing, counting, and/or sorting leukocytes from whole, undiluted blood samples.

  8. Microfluidic Device

    NASA Technical Reports Server (NTRS)

    Tai, Yu-Chong (Inventor); Zheng, Siyang (Inventor); Lin, Jeffrey Chun-Hui (Inventor); Kasdan, Harvey L. (Inventor)

    2016-01-01

    Described herein are particular embodiments relating to a microfluidic device that may be utilized for cell sensing, counting, and/or sorting. Particular aspects relate to a microfabricated device that is capable of differentiating single cell types from dense cell populations. One particular embodiment relates a device and methods of using the same for sensing, counting, and/or sorting leukocytes from whole, undiluted blood samples.

  9. Sealing device

    SciTech Connect

    Garcia-Crespo, Andres Jose

    2013-12-10

    A sealing device for sealing a gap between a dovetail of a bucket assembly and a rotor wheel is disclosed. The sealing device includes a cover plate configured to cover the gap and a retention member protruding from the cover plate and configured to engage the dovetail. The sealing device provides a seal against the gap when the bucket assemply is subjected to a centrifugal force.

  10. Structure cristalline du composé Hg3-xSbx(S+Se)2+xI2-x (x ≃ 0.1)

    PubMed Central

    Kars, Mohammed; Herrero, Adrian Gómez; Roisnel, Thierry; Rebbah, Allaoua; Otero-Diáz, L. Carlos

    2016-01-01

    Single crystals of the mercury chalcohalide Hg3-xSbx(S+Se)2+xI2-x (x ≃ 0.1) (mercury anti­mony sulfide selenide iodide), were grown by a chemical transport reaction. The structure contains three independent A (Hg/Sb) atoms; each atom is strongly covalently bonded with two X (Se/S) atoms to form approximately linear X–A–X units. The X–A–X units link to form A 4 X 4 rings, which are combined into infinite crankshaft-type bands running along the [100] direction. Four equatorial E (I/X = Se,S) atoms at relatively long distances complete the distorted octa­hedral coordination of A (Hg/Sb). The crystal under investigation was twinned by non-merohedry with a refined twin domain fraction of 0.814 (6):0.186 (6). The structure is isotypic with Hg3Se2I2 [Beck & Hedderich (2000 ▸). J. Solid State Chem. 151, 73–76], but the current determination reveals a coupled substitution, with partial replacement of Hg+2 by Sb+3, balanced by the equivalent substitution of I−1 by S−2 and Se−2. Bond-valence calculations are consistent with this relative substitution model. PMID:27006793

  11. Characterisation of Incommensurate Bi2+xSr2-xCuOz by X-Ray Powder Diffraction and Oxygen Content Determinations

    NASA Astrophysics Data System (ADS)

    Sinclair, D. C.; Irvine, J. T. S.; West, A. R.

    1990-11-01

    The composition-temperature stability region of the solid solution Bi2+xSr2-xCuOz, phase R, has been determined. At 800°C, 0.15

  12. Synthesis and radiation tolerance of Lu2-xCexTi2O7 pyrochlores

    NASA Astrophysics Data System (ADS)

    Xia, Y.; Liu, C. G.; Yang, D. Y.; Wen, J.; Liu, H.; Mu, P. C.; Li, Y. H.

    2016-11-01

    As a nonradioactive surrogate for Pu, Ce is selected to study the solubility and radiation tolerance in pyrochlore matrixes. In this paper, we synthesized a series of Lu2-xCexTi2O7 (x = 0-0.7) samples. X-ray diffraction, X-ray photoelectron spectroscopy and Raman spectroscopy were used to study the structure of Lu2-xCexTi2O7 (x = 0-0.7) with different Ce3+ content x. The results show that the maximum solubility of Ce3+ in Lu2Ti2O7 is 32 mol%. In order to study the radiation tolerance of these compounds, 400 keV Ne2+ was used to perform the irradiation experiments. The grazing incident X-ray diffraction patterns revealed that the radiation tolerance of the Lu2-xCexTi2O7 decreases with increasing Ce-content. This correlation between radiation tolerance and Ce-content was interpreted in terms of the antisite defect formation energies of Lu2-xCexTi2O7 (x = 0, 0.5, 1) based on the density functional theory.

  13. Design, Activation, and Operation of the J2-X Subscale Simulator (JSS)

    NASA Technical Reports Server (NTRS)

    Saunders, Grady P.; Raines, Nickey G.; Varner, Darrel G.

    2009-01-01

    The purpose of this paper is to give a detailed description of the design, activation, and operation of the J2-X Subscale Simulator (JSS) installed in Cell 1 of the E3 test facility at Stennis Space Center, MS (SSC). The primary purpose of the JSS is to simulate the installation of the J2-X engine in the A3 Subscale Rocket Altitude Test Facility at SSC. The JSS is designed to give aerodynamically and thermodynamically similar plume properties as the J2-X engine currently under development for use as the upper stage engine on the ARES I and ARES V spacecraft. The JSS is a scale pressure fed, LOX/GH fueled rocket that is geometrically similar to the J2-X from the throat to the nozzle exit plane (NEP) and is operated at the same oxidizer to fuel ratios and chamber pressures. This paper describes the heritage hardware used as the basis of the JSS design, the newly designed rocket hardware, igniter systems used, and the activation and operation of the JSS.

  14. Color-Space-Based Visual-MIMO for V2X Communication.

    PubMed

    Kim, Jai-Eun; Kim, Ji-Won; Park, Youngil; Kim, Ki-Doo

    2016-04-23

    In this paper, we analyze the applicability of color-space-based, color-independent visual-MIMO for V2X. We aim to achieve a visual-MIMO scheme that can maintain the original color and brightness while performing seamless communication. We consider two scenarios of GCM based visual-MIMO for V2X. One is a multipath transmission using visual-MIMO networking and the other is multi-node V2X communication. In the scenario of multipath transmission, we analyze the channel capacity numerically and we illustrate the significance of networking information such as distance, reference color (symbol), and multiplexing-diversity mode transitions. In addition, in the V2X scenario of multiple access, we may achieve the simultaneous multiple access communication without node interferences by dividing the communication area using image processing. Finally, through numerical simulation, we show the superior SER performance of the visual-MIMO scheme compared with LED-PD communication and show the numerical result of the GCM based visual-MIMO channel capacity versus distance.

  15. 16. Photocopy of photograph (original 51/2 x 31/4 inch print ...

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

    16. Photocopy of photograph (original 5-1/2 x 3-1/4 inch print located in the Recreation files, Mt. Baker-Snoqualmie N. F.). R. L. Fromme, photographer, 1941 INTERIOR OF MAIN ROOM, AUSTIN PASS SKI SHELTER. MT. BAKER NATIONAL FOREST. - Austin Pass Warming Hut, Washington Highway 542, Glacier, Whatcom County, WA

  16. Molecular mechanism of ATP binding and ion channel activation in P2X receptors

    SciTech Connect

    Hattori, Motoyuki; Gouaux, Eric

    2012-10-24

    P2X receptors are trimeric ATP-activated ion channels permeable to Na{sup +}, K{sup +} and Ca{sup 2+}. The seven P2X receptor subtypes are implicated in physiological processes that include modulation of synaptic transmission, contraction of smooth muscle, secretion of chemical transmitters and regulation of immune responses. Despite the importance of P2X receptors in cellular physiology, the three-dimensional composition of the ATP-binding site, the structural mechanism of ATP-dependent ion channel gating and the architecture of the open ion channel pore are unknown. Here we report the crystal structure of the zebrafish P2X4 receptor in complex with ATP and a new structure of the apo receptor. The agonist-bound structure reveals a previously unseen ATP-binding motif and an open ion channel pore. ATP binding induces cleft closure of the nucleotide-binding pocket, flexing of the lower body {beta}-sheet and a radial expansion of the extracellular vestibule. The structural widening of the extracellular vestibule is directly coupled to the opening of the ion channel pore by way of an iris-like expansion of the transmembrane helices. The structural delineation of the ATP-binding site and the ion channel pore, together with the conformational changes associated with ion channel gating, will stimulate development of new pharmacological agents.

  17. Bayesian Procedures for Prediction Analysis of Implication Hypotheses in 2 X 2 Contingency Tables.

    ERIC Educational Resources Information Center

    Lecoutre, Bruno; Charron, Camilo

    2000-01-01

    Illustrates procedures for prediction analysis in 2 X 2 contingency tables through the analyses of solutions of six types of problems associated with the acquisition of fractions. Reviews and extends confidence interval procedures previously proposed for an index of predictive efficiency of implication hypotheses. Compares frequentist coverage…

  18. X-ray structures define human P2X3 receptor gating cycle and antagonist action

    PubMed Central

    Mansoor, Steven E.; Lü, Wei; Oosterheert, Wout; Shekhar, Mrinal; Tajkhorshid, Emad; Gouaux, Eric

    2016-01-01

    Summary P2X receptors are trimeric, non-selective cation channels activated by ATP that play important roles in cardiovascular, neuronal and immune systems. Despite their central function in human physiology and as potential targets of therapeutic agents, there are no structures of human P2X receptors. Mechanisms of receptor desensitization and ion permeation, principles of antagonism, and complete structure of the pore-forming transmembrane domains remain unclear. We report x-ray crystal structures of human P2X3 receptor in apo/resting, agonist-bound/open-pore, agonist-bound/desensitized and antagonist-bound closed states. The open state structure harbors an intracellular motif we term the “cytoplasmic cap”, that stabilizes the open state of the ion channel pore and creates lateral, phospholipid-lined cytoplasmic fenestrations for water and ion egress. Competitive antagonists TNP-ATP and A-317491 stabilize the apo/resting state and reveal the interactions responsible for competitive inhibition. These structures illuminate the conformational rearrangements underpinning P2X receptor gating and provide a foundation for development of new pharmacologic agents. PMID:27626375

  19. Cohen's Linearly Weighted Kappa Is a Weighted Average of 2 x 2 Kappas

    ERIC Educational Resources Information Center

    Warrens, Matthijs J.

    2011-01-01

    An agreement table with [n as an element of N is greater than or equal to] 3 ordered categories can be collapsed into n - 1 distinct 2 x 2 tables by combining adjacent categories. Vanbelle and Albert ("Stat. Methodol." 6:157-163, 2009c) showed that the components of Cohen's weighted kappa with linear weights can be obtained from these n - 1…

  20. Superconductivity and disorder effect in TlNi2Se(2-x)S(x) compounds.

    PubMed

    Wang, Hangdong; Mao, Qianhui; Chen, Huimin; Su, Qiping; Dong, Chiheng; Khan, Rajwali; Yang, Jinhu; Chen, Bin; Fang, Minghu

    2015-10-07

    After our first discovery of multi-band superconductivity (SC) in the TlNi2Se2 crystal, we successfully grew a series of TlNi2Se(2-x)S(x) (0.0 ≤ x ≤ 2.0) single crystals. Measurements of resistivity, specific heat, and susceptibility were carried out on these crystals. Superconductivity with T(C) = 2.3 K was first observed in the TlNi2S2 crystal, which also appears to involve heavy electrons with an effective mass m* = 13-25 m(b), as inferred from the normal state electronic specific heat and the upper critical field, H(C2)(T). It was found that bulk SC and heavy-electron behavior is preserved in all the studied TlNi2Se(2-x)S(x) samples. In the mixed state, a novel change of the field dependence of the residual specific heat coefficient, γ(N)(H), occurs in TlNi2Se(2-x)S(x) with increasing S content. We also found that the T(C) value changes with the disorder degree induced by the partial substitution of S for Se, characterized by the residual resistivity ratio (RRR). Thus, the TlNi2Se(2-x)S(x) system provides a platform to study the effect of disorder on the multi-band SC.

  1. Superconductivity and disorder effect in TlNi2Se2-x S x compounds

    NASA Astrophysics Data System (ADS)

    Wang, Hangdong; Mao, Qianhui; Chen, Huimin; Su, Qiping; Dong, Chiheng; Khan, Rajwali; Yang, Jinhu; Chen, Bin; Fang, Minghu

    2015-10-01

    After our first discovery of multi-band superconductivity (SC) in the TlNi2Se2 crystal, we successfully grew a series of TlNi2Se2-x S x (0.0≤slant x≤slant 2.0 ) single crystals. Measurements of resistivity, specific heat, and susceptibility were carried out on these crystals. Superconductivity with {{T}\\text{C}}=2.3 K was first observed in the TlNi2S2 crystal, which also appears to involve heavy electrons with an effective mass m*=13 -25 {{m}\\text{b}} , as inferred from the normal state electronic specific heat and the upper critical field, {{H}\\text{C2}}(T) . It was found that bulk SC and heavy-electron behavior is preserved in all the studied TlNi2Se2-x S x samples. In the mixed state, a novel change of the field dependence of the residual specific heat coefficient, {γ\\text{N}}(H) , occurs in TlNi2Se2-x S x with increasing S content. We also found that the {{T}\\text{C}} value changes with the disorder degree induced by the partial substitution of S for Se, characterized by the residual resistivity ratio (RRR). Thus, the TlNi2Se2-x S x system provides a platform to study the effect of disorder on the multi-band SC.

  2. Gender Differences in the Factor Structure of the 2x2 Achievement Goal Framework

    ERIC Educational Resources Information Center

    Alkharusi, Hussain; Aldhafri, Said

    2010-01-01

    The present study examined gender differences in the factor structure of the 2x2 achievement goal framework using a multi-sample invariance analysis. A total of 117 male and 125 female undergraduate teacher education students completed Elliot and Murayama's (2008) Achievement Goal Questionnaire-Revised (AGQ-R). Results provided empirical evidence…

  3. Understanding Student Goal Orientation Tendencies to Predict Student Performance: A 2x2 Achievement Goal Orientation

    ERIC Educational Resources Information Center

    Miller, Mark Alan

    2013-01-01

    The study tested the 2X2 model of the Achievement Goal Orientation (AGO) theory in a military technical training environment while using the Air Force Officers Qualifying Test's academic aptitude score to control for the differences in the students' academic aptitude. The study method was quantitative and the design was correlational.…

  4. X-ray structures define human P2X3 receptor gating cycle and antagonist action

    NASA Astrophysics Data System (ADS)

    Mansoor, Steven E.; Lü, Wei; Oosterheert, Wout; Shekhar, Mrinal; Tajkhorshid, Emad; Gouaux, Eric

    2016-10-01

    P2X receptors are trimeric, non-selective cation channels activated by ATP that have important roles in the cardiovascular, neuronal and immune systems. Despite their central function in human physiology and although they are potential targets of therapeutic agents, there are no structures of human P2X receptors. The mechanisms of receptor desensitization and ion permeation, principles of antagonism, and complete structures of the pore-forming transmembrane domains of these receptors remain unclear. Here we report X-ray crystal structures of the human P2X3 receptor in apo/resting, agonist-bound/open-pore, agonist-bound/closed-pore/desensitized and antagonist-bound/closed states. The open state structure harbours an intracellular motif we term the ‘cytoplasmic cap’, which stabilizes the open state of the ion channel pore and creates lateral, phospholipid-lined cytoplasmic fenestrations for water and ion egress. The competitive antagonists TNP-ATP and A-317491 stabilize the apo/resting state and reveal the interactions responsible for competitive inhibition. These structures illuminate the conformational rearrangements that underlie P2X receptor gating and provide a foundation for the development of new pharmacological agents.

  5. Window type: paired 2x4 multipaned steel windows flanked by 1x4 ...

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

    Window type: paired 2x4 multipaned steel windows flanked by 1x4 multipaned steel casements, breaking building corner. Raised panel door front entry also illustrated. Ground floor detail Building 19, facing north - Harbor Hills Housing Project, 26607 Western Avenue, Lomita, Los Angeles County, CA

  6. Window types: (from left to right) Pair of 2x2 multipaned ...

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

    Window types: (from left to right) Pair of 2x2 multipaned steel casements; triplet of 1x4 multipaned steel casements (center panel fixed); 1x3 multipaned steel casements. Building 20, facing southwest - Harbor Hills Housing Project, 26607 Western Avenue, Lomita, Los Angeles County, CA

  7. Color-Space-Based Visual-MIMO for V2X Communication †

    PubMed Central

    Kim, Jai-Eun; Kim, Ji-Won; Park, Youngil; Kim, Ki-Doo

    2016-01-01

    In this paper, we analyze the applicability of color-space-based, color-independent visual-MIMO for V2X. We aim to achieve a visual-MIMO scheme that can maintain the original color and brightness while performing seamless communication. We consider two scenarios of GCM based visual-MIMO for V2X. One is a multipath transmission using visual-MIMO networking and the other is multi-node V2X communication. In the scenario of multipath transmission, we analyze the channel capacity numerically and we illustrate the significance of networking information such as distance, reference color (symbol), and multiplexing-diversity mode transitions. In addition, in the V2X scenario of multiple access, we may achieve the simultaneous multiple access communication without node interferences by dividing the communication area using image processing. Finally, through numerical simulation, we show the superior SER performance of the visual-MIMO scheme compared with LED-PD communication and show the numerical result of the GCM based visual-MIMO channel capacity versus distance. PMID:27120603

  8. Structural basis for subtype-specific inhibition of the P2X7 receptor

    SciTech Connect

    Karasawa, Akira; Kawate, Toshimitsu

    2016-12-09

    The P2X7 receptor is a non-selective cation channel activated by extracellular adenosine triphosphate (ATP). Chronic activation of P2X7 underlies many health problems such as pathologic pain, yet we lack effective antagonists due to poorly understood mechanisms of inhibition. Here we present crystal structures of a mammalian P2X7 receptor complexed with five structurally-unrelated antagonists. Unexpectedly, these drugs all bind to an allosteric site distinct from the ATP-binding pocket in a groove formed between two neighboring subunits. This novel drug-binding pocket accommodates a diversity of small molecules mainly through hydrophobic interactions. Functional assays propose that these compounds allosterically prevent narrowing of the drug-binding pocket and the turret-like architecture during channel opening, which is consistent with a site of action distal to the ATP-binding pocket. These novel mechanistic insights will facilitate the development of P2X7-specific drugs for treating human diseases.

  9. Structural insights into the nucleotide base specificity of P2X receptors

    PubMed Central

    Kasuya, Go; Fujiwara, Yuichiro; Tsukamoto, Hisao; Morinaga, Satoshi; Ryu, Satoshi; Touhara, Kazushige; Ishitani, Ryuichiro; Furutani, Yuji; Hattori, Motoyuki; Nureki, Osamu

    2017-01-01

    P2X receptors are trimeric ATP-gated cation channels involved in diverse physiological processes, ranging from muscle contraction to nociception. Despite the recent structure determination of the ATP-bound P2X receptors, the molecular mechanism of the nucleotide base specificity has remained elusive. Here, we present the crystal structure of zebrafish P2X4 in complex with a weak affinity agonist, CTP, together with structure-based electrophysiological and spectroscopic analyses. The CTP-bound structure revealed a hydrogen bond, between the cytosine base and the side chain of the basic residue in the agonist binding site, which mediates the weak but significant affinity for CTP. The cytosine base is further recognized by two main chain atoms, as in the ATP-bound structure, but their bond lengths seem to be extended in the CTP-bound structure, also possibly contributing to the weaker affinity for CTP over ATP. This work provides the structural insights for the nucleotide base specificity of P2X receptors. PMID:28332633

  10. Direct observation of dynamic charge stripes in La2-xSrxNiO4.

    PubMed

    Anissimova, S; Parshall, D; Gu, G D; Marty, K; Lumsden, M D; Chi, Songxue; Fernandez-Baca, J A; Abernathy, D L; Lamago, D; Tranquada, J M; Reznik, D

    2014-03-17

    The insulator-to-metal transition continues to be a challenging subject, especially when electronic correlations are strong. In layered compounds, such as La2-xSrxNiO4 and La2-xBaxCuO4, the doped charge carriers can segregate into periodically spaced charge stripes separating narrow domains of antiferromagnetic order. Although there have been theoretical proposals of dynamically fluctuating stripes, direct spectroscopic evidence of charge-stripe fluctuations has been lacking. Here we report the detection of critical lattice fluctuations, driven by charge-stripe correlations, in La2-xSrxNiO4 using inelastic neutron scattering. This scattering is detected at large momentum transfers where the magnetic form factor suppresses the spin fluctuation signal. The lattice fluctuations associated with the dynamic charge stripes are narrow in q and broad in energy. They are strongest near the charge-stripe melting temperature. Our results open the way towards the quantitative theory of dynamic stripes and for directly detecting dynamical charge stripes in other strongly correlated systems, including high-temperature superconductors such as La2-xSrxCuO4.

  11. Direct observation of dynamic charge stripes in La2-xSrxNiO4

    NASA Astrophysics Data System (ADS)

    Anissimova, S.; Parshall, D.; Gu, G. D.; Marty, K.; Lumsden, M. D.; Chi, Songxue; Fernandez-Baca, J. A.; Abernathy, D. L.; Lamago, D.; Tranquada, J. M.; Reznik, D.

    2014-03-01

    The insulator-to-metal transition continues to be a challenging subject, especially when electronic correlations are strong. In layered compounds, such as La2-xSrxNiO4 and La2-xBaxCuO4, the doped charge carriers can segregate into periodically spaced charge stripes separating narrow domains of antiferromagnetic order. Although there have been theoretical proposals of dynamically fluctuating stripes, direct spectroscopic evidence of charge-stripe fluctuations has been lacking. Here we report the detection of critical lattice fluctuations, driven by charge-stripe correlations, in La2-xSrxNiO4 using inelastic neutron scattering. This scattering is detected at large momentum transfers where the magnetic form factor suppresses the spin fluctuation signal. The lattice fluctuations associated with the dynamic charge stripes are narrow in q and broad in energy. They are strongest near the charge-stripe melting temperature. Our results open the way towards the quantitative theory of dynamic stripes and for directly detecting dynamical charge stripes in other strongly correlated systems, including high-temperature superconductors such as La2-xSrxCuO4.

  12. Procrastination and the 2 x 2 Achievement Goal Framework in Malaysian Undergraduate Students

    ERIC Educational Resources Information Center

    Ganesan, Rajalakshmi; Mamat, Norul Hidayah Bt; Mellor, David; Rizzuto, Laura; Kolar, Christina

    2014-01-01

    The present study investigated academic procrastination in the context of the 2 x 2 goal achievement theoretical framework within a population of 450 Malaysian undergraduate students, aged 18 to 25 years. Participants completed the Achievement Goal Questionnaire and the Tuckman Procrastination Test. Approach dimensions of both the mastery and…

  13. Extending the 2 x 2 Achievement Goal Framework: Development of a Measure of Scientific Achievement Goals

    ERIC Educational Resources Information Center

    Deemer, Eric D.; Carter, Alice P.; Lobrano, Michael T.

    2010-01-01

    The current research sought to extend the 2 x 2 achievement goal framework by developing and testing the Achievement Goals for Research Scale (AGRS). Participants (N = 317) consisted of graduate students in the life, physical, and behavioral sciences. A principal components analysis (PCA) extracted five components accounting for 72.59% of the…

  14. System Engineering for J-2X Development: The Simpler, the Better

    NASA Technical Reports Server (NTRS)

    Kelly, William M.; Greasley, Paul; Greene, William D.; Ackerman, Peter

    2008-01-01

    The Ares I and Ares V Vehicles will utilize the J-2X rocket engine developed for NASA by the Pratt and Whitney Rocketdyne Company (PWR) as the upper stage engine (USE). The J-2X is an improved higher power version of the original J-2 engine used for Apollo. System Engineering (SE) facilitates direct and open discussions of issues and problems. This simple idea is often overlooked in large, complex engineering development programs. Definition and distribution of requirements from the engine level to the component level is controlled by Allocation Reports which breaks down numerical design objectives (weight, reliability, etc.) into quanta goals for each component area. Linked databases of design and verification requirements help eliminate redundancy and potential mistakes inherent in separated systems. Another tool, the Architecture Design Description (ADD), is used to control J-2X system architecture and effectively communicate configuration changes to those involved in the design process. But the proof of an effective process is in successful program accomplishment. SE is the methodology being used to meet the challenge of completing J-2X engine certification 2 years ahead of any engine program ever developed at PWR. This paper describes the simple, better SE tools and techniques used to achieve this success.

  15. Structural basis for subtype-specific inhibition of the P2X7 receptor

    PubMed Central

    Karasawa, Akira; Kawate, Toshimitsu

    2016-01-01

    The P2X7 receptor is a non-selective cation channel activated by extracellular adenosine triphosphate (ATP). Chronic activation of P2X7 underlies many health problems such as pathologic pain, yet we lack effective antagonists due to poorly understood mechanisms of inhibition. Here we present crystal structures of a mammalian P2X7 receptor complexed with five structurally-unrelated antagonists. Unexpectedly, these drugs all bind to an allosteric site distinct from the ATP-binding pocket in a groove formed between two neighboring subunits. This novel drug-binding pocket accommodates a diversity of small molecules mainly through hydrophobic interactions. Functional assays propose that these compounds allosterically prevent narrowing of the drug-binding pocket and the turret-like architecture during channel opening, which is consistent with a site of action distal to the ATP-binding pocket. These novel mechanistic insights will facilitate the development of P2X7-specific drugs for treating human diseases. DOI: http://dx.doi.org/10.7554/eLife.22153.001 PMID:27935479

  16. The 2 x 2 Model of Perfectionism: A Comparison across Asian Canadians and European Canadians

    ERIC Educational Resources Information Center

    Franche, Veronique; Gaudreau, Patrick; Miranda, Dave

    2012-01-01

    The 2 x 2 model of perfectionism posits that the 4 within-person combinations of self-oriented and socially prescribed perfectionism (i.e., pure SOP, mixed perfectionism, pure SPP, and nonperfectionism) can be distinctively associated with psychological adjustment. This study examined whether the relationship between the 4 subtypes of…

  17. 2. X15 RUN UP AREA (Jan 59). A sharp, higher ...

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

    2. X-15 RUN UP AREA (Jan 59). A sharp, higher altitide low oblique aerial view to the north, showing runway, at far left; X-15 Engine Test Complex in the center. This view predates construction of observation bunkers. - Edwards Air Force Base, X-15 Engine Test Complex, Rogers Dry Lake, east of runway between North Base & South Base, Boron, Kern County, CA

  18. Testing of the J-2X Augmented Spark Igniter (ASI) and Its Electronics

    NASA Technical Reports Server (NTRS)

    Osborne, Robin

    2015-01-01

    Reliable operation of the spark ignition system electronics in the J-2X Augmented Spark Igniter (ASI) is imperative in assuring ASI ignition and subsequent Main Combustion Chamber (MCC) ignition events are reliable in the J-2X Engine. Similar to the man-rated J-2 and RS-25 engines, the J-2X ignition system electronics are equipped with spark monitor outputs intended to indicate that the spark igniters are properly energized and sparking. To better understand anomalous spark monitor data collected on the J-2X development engines at NASA Stennis Space Center (SSC), a comprehensive subsystem study of the engine's low- and high-tension spark ignition system electronics was conducted at NASA Marshall Space Flight Center (MSFC). Spark monitor output data were compared to more detailed spark diagnostics to determine if the spark monitor was an accurate indication of actual sparking events. In addition, ignition system electronics data were closely scrutinized for any indication of an electrical discharge in some location other than the firing tip of the spark igniter - a problem not uncommon in the development of high voltage ignition systems.

  19. Synthesis, characterization, and photocatalytic activity of TiO(2-x)N(x) nanocatalyst.

    PubMed

    Wang, Y Q; Yu, X J; Sun, D Z

    2007-06-01

    Nitrogen-doped titanium dioxide powders were prepared by wet method, that is, the hydrolysis of acidic tetra-butyl titanate using aqueous ammonia solution, followed by calcination at temperatures about 350 degrees C. The catalysts exhibited photocatalytic activity in the visible light region owing to N-doping. The light absorption onset of TiO(2-x)N(x) was shifted to the visible region at 459 nm compared to 330 nm of pure TiO(2). An obvious decrease in the band gap was observed by the optical absorption spectroscopy, which resulted from N2p localized states above the valence band of TiO(2-x)N(x) (compared to TiO(2)). The TiO(2-x)N(x) catalyst was characterized to be anatase with oxygen-deficient stoichiometry by X-ray diffraction (XRD), surface photovoltage spectroscopy (SPS) and X-ray photoelectron spectroscopy (XPS). The binding energy of N1s measured by XPS characterization was 396.6 eV (TiN bonds, beta-N) and 400.9 eV (NN bonds, gamma-N(2)), respectively. The photocatalytic activity of TiO(2-x)N(x) under visible light was induced by the formation of beta-N in the structure. Photocatalytic decomposition of benzoic acid solutions was carried out in the ultraviolet and visible (UV-vis) light region, and the TiO(2-x)N(x) catalyst showed higher activity than pure TiO(2).

  20. Critical role of P2X7 receptors in the neuroinflammation and cognitive dysfunction after surgery.

    PubMed

    Zheng, Bin; Lai, Renchun; Li, Jun; Zuo, Zhiyi

    2017-03-01

    Postoperative cognitive dysfunction worsens patient outcome after surgery. Neuroinflammation is a critical neuropathological process for it. We determined the role of P2X7 receptors, proteins that participate in inflammatory response, in the neuroinflammation induction after surgery, and whether the choice of volatile anesthetics affects its occurrence. Eight-week old C57BL/6J or P2X7 receptor knockout male mice were subjected to right carotid arterial exposure under anesthesia with 1.8% isoflurane, 2.5% sevoflurane or 10% desflurane. They were tested by Barnes maze and fear conditioning from 2weeks after the surgery. Hippocampus was harvested 6h, 24h and 7days after the surgery for immunohistochemical staining and Western blotting. Mice with surgery under anesthesia with isoflurane, sevoflurane or desflurane took longer than control mice to identify the target box 1 or 8days after the training sessions in Barnes maze. Mice anesthetized by isoflurane or sevoflurane, but not by desflurane, had less freezing behavior than control mice in fear conditioning test. Mice with surgery and anesthesia had increased ionized calcium binding adapter molecule 1 and interleukin 1β in the hippocampus but this increase was smaller in mice anesthetized with desflurane than mice anesthetized with isoflurane. Mice with surgery had increased P2X7 receptors and its downstream molecule caspase 1. Inhibition or knockout of P2X7 receptors attenuated surgery and anesthesia-induced neuroinflammation and cognitive impairment. We conclude that surgery under desflurane anesthesia may have reduced neuroinflammation and cognitive impairment compared with surgery under isoflurane anesthesia. P2X7 receptors may mediate the neuroinflammation and cognitive impairment after surgery.

  1. P2X7 receptor promotes intestinal inflammation in chemically induced colitis and triggers death of mucosal regulatory T cells.

    PubMed

    Figliuolo, Vanessa R; Savio, Luiz Eduardo Baggio; Safya, Hanaa; Nanini, Hayandra; Bernardazzi, Cláudio; Abalo, Alessandra; de Souza, Heitor S P; Kanellopoulos, Jean; Bobé, Pierre; Coutinho, Cláudia M L M; Coutinho-Silva, Robson

    2017-03-07

    P2X7 receptor activation contributes to inflammation development in different pathologies. We previously reported that the P2X7 receptor is over-expressed in the gut mucosa of patients with inflammatory bowel disease, and that P2X7 inhibition protects against chemically induced colitis. Here, we investigated in detail the role of the P2X7 receptor in inflammatory bowel disease development, by treating P2X7 knockout (KO) and WT mice with two different (and established) colitis inductors. P2X7 KO mice were protected against gut inflammation induced by 2,4,6-trinitrobenzenesulfonic acid or oxazolone, with no weight loss or gut histological alterations after treatment. P2X7 receptor knockout induced regulatory T cell accumulation in the colon, as evaluated by qRT-PCR for FoxP3 expression and immunostaining for CD90/CD45RB(low). Flow cytometry analysis of mesenteric lymph node cells showed that P2X7 activation (by ATP) triggered regulatory T cell death. In addition, such cells from P2X7 KO mice expressed more CD103, suggesting increased migration of regulatory T cells to the colon (relative to the WT). Our results show that the P2X7 has a key role during inflammation development in inflammatory bowel disease, by triggering the death and retention in the mesenteric lymph nodes of regulatory T cells that would otherwise promote immune system tolerance in the gut.

  2. Co-Expression of Wild-Type P2X7R with Gln460Arg Variant Alters Receptor Function

    PubMed Central

    Aprile-Garcia, Fernando; Metzger, Michael W.; Paez-Pereda, Marcelo; Stadler, Herbert; Acuña, Matías; Liberman, Ana C.; Senin, Sergio A.; Gerez, Juan; Hoijman, Esteban; Refojo, Damian; Mitkovski, Mišo; Panhuysen, Markus; Stühmer, Walter; Holsboer, Florian; Deussing, Jan M.; Arzt, Eduardo

    2016-01-01

    The P2X7 receptor is a member of the P2X family of ligand-gated ion channels. A single-nucleotide polymorphism leading to a glutamine (Gln) by arginine (Arg) substitution at codon 460 of the purinergic P2X7 receptor (P2X7R) has been associated with mood disorders. No change in function (loss or gain) has been described for this SNP so far. Here we show that although the P2X7R-Gln460Arg variant per se is not compromised in its function, co-expression of wild-type P2X7R with P2X7R-Gln460Arg impairs receptor function with respect to calcium influx, channel currents and intracellular signaling in vitro. Moreover, co-immunoprecipitation and FRET studies show that the P2X7R-Gln460Arg variant physically interacts with P2X7R-WT. Specific silencing of either the normal or polymorphic variant rescues the heterozygous loss of function phenotype and restores normal function. The described loss of function due to co-expression, unique for mutations in the P2RX7 gene so far, explains the mechanism by which the P2X7R-Gln460Arg variant affects the normal function of the channel and may represent a mechanism of action for other mutations. PMID:26986975

  3. Post-translational allosteric activation of the P2X7 receptor through glycosaminoglycan chains of CD44 proteoglycans

    PubMed Central

    Moura, GEDD; Lucena, SV; Lima, MA; Nascimento, FD; Gesteira, TF; Nader, HB; Paredes-Gamero, EJ; Tersariol, ILS

    2015-01-01

    Here, we present evidence for the positive allosteric modulation of the P2X7 receptor through glycosaminoglycans (GAGs) in CHO (cell line derived from the ovary of the Chinese hamster) cells. The marked potentiation of P2X7 activity through GAGs in the presence of non-saturating agonists concentrations was evident with the endogenous expression of the receptor in CHO cells. The presence of GAGs on the surface of CHO cells greatly increased the sensitivity to adenosine 5′-triphosphate and changed the main P2X7 receptor kinetic parameters EC50, Hill coefficient and Emax. GAGs decreased the allosteric inhibition of P2X7 receptor through Mg2+. GAGs activated P2X7 receptor-mediated cytoplasmic Ca2+ influx and pore formation. Consequently, wild-type CHO-K1 cells were 2.5-fold more sensitive to cell death induced through P2X7 agonists than mutant CHO-745 cells defective in GAGs biosynthesis. In the present study, we provide the first evidence that the P2X7 receptor interacts with CD44 on the CHO-K1 cell surface. Thus, these data demonstrated that GAGs positively modulate the P2X7 receptor, and sCD44 is a part of a regulatory positive feedback loop linking P2X7 receptor activation for the intracellular response mediated through P2X7 receptor stimulation. PMID:27551441

  4. P2X7 purinoceptor alterations in dystrophic mdx mouse muscles: relationship to pathology and potential target for treatment.

    PubMed

    Young, Christopher N J; Brutkowski, Wojciech; Lien, Chun-Fu; Arkle, Stephen; Lochmüller, Hanns; Zabłocki, Krzysztof; Górecki, Dariusz C

    2012-05-01

    Duchenne muscular dystrophy (DMD) is a lethal inherited muscle disorder. Pathological characteristics of DMD skeletal muscles include, among others, abnormal Ca(2+) homeostasis and cell signalling. Here, in the mdx mouse model of DMD, we demonstrate significant P2X7 receptor abnormalities in isolated primary muscle cells and cell lines and in dystrophic muscles in vivo. P2X7 mRNA expression in dystrophic muscles was significantly up-regulated but without alterations of specific splice variant patterns. P2X7 protein was also up-regulated and this was associated with altered function of P2X7 receptors producing increased responsiveness of cytoplasmic Ca(2+) and extracellular signal-regulated kinase (ERK) phosphorylation to purinergic stimulation and altered sensitivity to NAD. Ca(2+) influx and ERK signalling were stimulated by ATP and BzATP, inhibited by specific P2X7 antagonists and insensitive to ivermectin, confirming P2X7 receptor involvement. Despite the presence of pannexin-1, prolonged P2X7 activation did not trigger cell permeabilization to propidium iodide or Lucifer yellow. In dystrophic mice, in vivo treatment with the P2X7 antagonist Coomassie Brilliant Blue reduced the number of degeneration-regeneration cycles in mdx skeletal muscles. Altered P2X7 expression and function is thus an important feature in dystrophic mdx muscle and treatments aiming to inhibit P2X7 receptor might slow the progression of this disease.

  5. BRAKE DEVICE

    DOEpatents

    O'Donnell, T.J.

    1959-03-10

    A brake device is described for utilization in connection with a control rod. The device comprises a pair of parallelogram link mechanisms, a control rod moveable rectilinearly therebetween in opposite directions, and shoes resiliently supported by the mechanism for frictional engagement with the control rod.

  6. Josephson Devices

    NASA Astrophysics Data System (ADS)

    Barone, Antonio; Pagano, Sergio

    In this chapter we briefly review the main applications of Josephson effect together with the most successful devices realized. We will give an overview of the various devices, providing also some basic concepts of the underlying physical mechanisms involved, and the associated limit performances. Some considerations on the concrete possibilities of successful "market ready" implementation will also be given.

  7. Electrochromic devices

    DOEpatents

    Allemand, Pierre M.; Grimes, Randall F.; Ingle, Andrew R.; Cronin, John P.; Kennedy, Steve R.; Agrawal, Anoop; Boulton, Jonathan M.

    2001-01-01

    An electrochromic device is disclosed having a selective ion transport layer which separates an electrochemically active material from an electrolyte containing a redox active material. The devices are particularly useful as large area architectural and automotive glazings due to there reduced back reaction.

  8. Optoelectronic devices

    NASA Astrophysics Data System (ADS)

    Sperling, Leslie H.; Murphy, Clarence J.; Rosen, Warren A.; Jain, Himanshu

    1990-07-01

    This invention relates to acrylic polymers and more specifically to polyacrylamides and polyacrylates such as poly(2-((N-2-methyl-5-nitrophenylamino) ethyl acrylate)) and poly((N-2-methyl-4-nitrophenyl)acrylamide). These acrylic polymers are particularly useful as nonlinear optical components in various electrical devices for processing optical signals including interferometors, optical switches, optical amplifiers, generators, computational devices and the like.

  9. PLASMA DEVICE

    DOEpatents

    Gow, J.D.; Wilcox, J.M.

    1961-12-26

    A device is designed for producing and confining highenergy plasma from which neutrons are generated in copious quantities. A rotating sheath of electrons is established in a radial electric field and axial magnetic field produced within the device. The electron sheath serves as a strong ionizing medium to gas introdueed thereto and also functions as an extremely effective heating mechanism to the resulting plasma. In addition, improved confinement of the plasma is obtained by ring magnetic mirror fields produced at the ends of the device. Such ring mirror fields are defined by the magnetic field lines at the ends of the device diverging radially outward from the axis of the device and thereafter converging at spatial annular surfaces disposed concentrically thereabout. (AFC)

  10. Preparation and characterization of Al{sub 2x}In{sub 2−2x}O{sub 3} films deposited on MgO (1 0 0) by MOCVD

    SciTech Connect

    Li, Zhao; Ma, Jin Zhao, Cansong; Du, Xuejian; Mi, Wei; Luan, Caina; Feng, Xianjin

    2015-07-15

    Highlights: • Ternary Al{sub 2x}In{sub 2−2x}O{sub 3} alloy films were deposited on MgO (1 0 0) by MOCVD. • The microstructure of the Al{sub 2x}In{sub 2−2x}O{sub 3} films were studied upon HRTEM. • Al{sub 2x}In{sub 2−2x}O{sub 3} alloy films exhibited great optical transparency in the visible wavelength range. • The band gap of the Al{sub 2x}In{sub 2−2x}O{sub 3} films can be modulated by controlling the Al contents in the samples. - Abstract: The ternary Al{sub 2x}In{sub 2−2x}O{sub 3} films with different compositions x[Al/(Al + In) atomic ratio] have been fabricated on the MgO (1 0 0) substrates by the metal organic chemical vapor deposition (MOCVD) method. The influence of different Al contents on the structural, optical and electrical properties of Al{sub 2x}In{sub 2−2x}O{sub 3} films has been studied. The structural studies reveal a change from single crystalline structure of cubic In{sub 2}O{sub 3} to amorphous as the Al content increases. The average transmittances of all samples in the visible range are over 80%. The optical band gap is observed to increase monotonically from 3.67 to 5.38 eV as the Al content increases from 0.1 to 0.9.

  11. On the role of P2X(7) receptors in dopamine nerve cell degeneration in a rat model of Parkinson's disease: studies with the P2X(7) receptor antagonist A-438079.

    PubMed

    Marcellino, Daniel; Suárez-Boomgaard, Diana; Sánchez-Reina, María Dolores; Aguirre, José A; Yoshitake, Takashi; Yoshitake, Shimako; Hagman, Beth; Kehr, Jan; Agnati, Luigi F; Fuxe, Kjell; Rivera, Alicia

    2010-06-01

    The role of the ATP-gated receptor, P2X(7), has been evaluated in the unilateral 6-OHDA rat model of Parkinson's disease using the P2X(7) competitive antagonist A-438079. Nigral P2X(7) immunoreactivity was mainly located in microglia but also in astroglia. A-438079 partially but significantly prevented the 6-OHDA-induced depletion of striatal DA stores. However, this was not associated with a reduction of DA cell loss. Blockade of P2X(7) receptors may represent a novel protective strategy for striatal DA terminals in Parkinson's disease and warrants further future investigation.

  12. Functional polymorphisms in the P2X7 receptor gene are associated with stress fracture injury.

    PubMed

    Varley, Ian; Greeves, Julie P; Sale, Craig; Friedman, Eitan; Moran, Daniel S; Yanovich, Ran; Wilson, Peter J; Gartland, Alison; Hughes, David C; Stellingwerff, Trent; Ranson, Craig; Fraser, William D; Gallagher, James A

    2016-03-01

    Military recruits and elite athletes are susceptible to stress fracture injuries. Genetic predisposition has been postulated to have a role in their development. The P2X7 receptor (P2X7R) gene, a key regulator of bone remodelling, is a genetic candidate that may contribute to stress fracture predisposition. The aim of this study is to evaluate the putative contribution of P2X7R to stress fracture injury in two separate cohorts, military personnel and elite athletes. In 210 Israeli Defense Forces (IDF) military conscripts, stress fracture injury was diagnosed (n = 43) based on symptoms and a positive bone scan. In a separate cohort of 518 elite athletes, self-reported medical imaging scan-certified stress fracture injuries were recorded (n = 125). Non-stress fracture controls were identified from these cohorts who had a normal bone scan or no history or symptoms of stress fracture injury. Study participants were genotyped for functional SNPs within the P2X7R gene using proprietary fluorescence-based competitive allele-specific PCR assay. Pearson's chi-squared (χ (2)) tests, corrected for multiple comparisons, were used to assess associations in genotype frequencies. The variant allele of P2X7R SNP rs3751143 (Glu496Ala-loss of function) was associated with stress fracture injury, whilst the variant allele of rs1718119 (Ala348Thr-gain of function) was associated with a reduced occurrence of stress fracture injury in military conscripts (P < 0.05). The association of the variant allele of rs3751143 with stress fractures was replicated in elite athletes (P < 0.05), whereas the variant allele of rs1718119 was also associated with reduced multiple stress fracture cases in elite athletes (P < 0.05). The association between independent P2X7R polymorphisms with stress fracture prevalence supports the role of a genetic predisposition in the development of stress fracture injury.

  13. A Dual Role for P2X7 Receptor during Porphyromonas gingivalis Infection

    PubMed Central

    Ramos-Junior, E.S.; Morandini, A.C.; Almeida-da-Silva, C.L.C.; Franco, E.J.; Potempa, J.; Nguyen, K.A.; Oliveira, A.C.; Zamboni, D.S.; Ojcius, D.M.; Scharfstein, J.

    2015-01-01

    Emerging evidence suggests a role for purinergic signaling in the activation of multiprotein intracellular complexes called inflammasomes, which control the release of potent inflammatory cytokines, such as interleukin (IL) -1β and -18. Porphyromonas gingivalis is intimately associated with periodontitis and is currently considered one of the pathogens that can subvert the immune system by limiting the activation of the NLRP3 inflammasome. We recently showed that P. gingivalis can dampen eATP-induced IL-1β secretion by means of its fimbriae in a purinergic P2X7 receptor–dependent manner. Here, we further explore the role of this purinergic receptor during eATP-induced IL-1β processing and secretion by P. gingivalis–infected macrophages. We found that NLRP3 was necessary for eATP-induced IL-1β secretion as well as for caspase 1 activation irrespective of P. gingivalis fimbriae. Additionally, although the secretion of IL-1β from P. gingivalis–infected macrophages was dependent on NLRP3, its adaptor protein ASC, or caspase 1, the cleavage of intracellular pro-IL-1β to the mature form was found to occur independently of NLRP3, its adaptor protein ASC, or caspase 1. Our in vitro findings revealed that P2X7 receptor has a dual role, being critical not only for eATP-induced IL-1β secretion but also for intracellular pro-IL-1β processing. These results were relevant in vivo since P2X7 receptor expression was upregulated in a P. gingivalis oral infection model, and reduced IFN-γ and IL-17 were detected in draining lymph node cells from P2rx7-/- mice. Furthermore, we demonstrated that P2X7 receptor and NLRP3 transcription were modulated in human chronic periodontitis. Overall, we conclude that the P2X7 receptor has a role in periodontal immunopathogenesis and suggest that targeting of the P2X7/NLRP3 pathway should be considered in future therapeutic interventions in periodontitis. PMID:26152185

  14. Unstable spin-ice order in the stuffed metallic pyrochlore Pr2+xIr2-xO7-δ

    DOE PAGES

    MacLaughlin, D. E.; Bernal, O. O.; Shu, Lei; ...

    2015-08-24

    Specific heat, elastic neutron scattering, and muon spin rotation experiments have been carried out on a well-characterized sample of “stuffed” (Pr-rich) Pr2+xIr2-xO7-δ. Elastic neutron scattering shows the onset of long-range spin-ice “2-in/2-out” magnetic order at 0.93 kelvin, with an ordered moment of 1.7(1) Bohr magnetons per Pr ion at low temperatures. Approximate lower bounds on the correlation length and correlation time in the ordered state are 170 angstroms and 0.7 nanosecond, respectively. Muon spin rotation experiments yield an upper bound 2.6(7) milliteslas on the local field B4floc at the muon site, which is nearly two orders of magnitude smaller thanmore » the expected dipolar field for long-range spin-ice ordering of 1.7-Bohr magneton moments (120–270 milliteslas, depending on the muon site). This shortfall is due in part to splitting of the non-Kramers crystal-field ground-state doublets of near-neighbor Pr3+ ions by the positive-muon-induced lattice distortion. For this to be the only effect, however, ~160 Pr moments out to a distance of ~14 angstroms must be suppressed. An alternative scenario—one consistent with the observed reduced nuclear hyperfine Schottky anomaly in the specific heat—invokes slow correlated Pr-moment fluctuations in the ordered state that average B4floc on the μSR time scale (~10-7 second), but are static on the time scale of the elastic neutron scattering experiments (~10-9 second). In this picture, the dynamic muon relaxation suggests a Pr3+ 4f correlation time of a few nanoseconds, which should be observable in a neutron spin echo experiment.« less

  15. Reaction of plutonium dioxide with water: formation and properties of PuO(2+x)

    PubMed

    Haschke; Allen; Morales

    2000-01-14

    Results show that PuO(2+x), a high-composition (x 2+x) are consistent with a failure to observe the phase in earlier studies. Perplexing aspects of plutonium oxide chemistry can now be explained.

  16. Characterization of M2X formed during 5 MeV Fe2+ irradiation

    NASA Astrophysics Data System (ADS)

    Getto, E.; Sun, K.; Was, G. S.

    2017-03-01

    The growth of M2X phase in HT9 irradiated to high dpa was explored using self-ion irradiation. HT9 was pre-implanted with 10 appm He and irradiated with a raster-scanned Fe2+ beam with a damage rate of ∼1 × 10-3 dpa/s at 460 °C. The precipitation of M2X was observed and a combination of high resolution transmission electron microscopy (HRTEM), energy filtered transmission electron microscopy (EFTEM) and diffraction analysis was used to characterize the Cr-rich carbide observed at 250 dpa and above. Cr2C was determined to be semi-coherent with the matrix such that [ 100 ] Cr2 C / /[100]α and [ 001 ] Cr2 C / /[ 10 1 bar ] α .with a = 2.71 Å and c = 2.82 Å.

  17. Optical Characterization of Multilayer Thin Film Cu_xIn_2-xSe_2^*

    NASA Astrophysics Data System (ADS)

    Raffaelle, R. P.; Friedfeld, R.; Mantovani, J. G.

    1996-03-01

    Cu_xIn_2-xSe2 is one of the most promising thin film solar cell materials, due to its ideal optical and electrical properties. We have been electrochemically depositing multilayer structures based on the Cu_xIn_2-xSe2 system. The interest in multilayer structures is due to their proposed use in increasing thin film solar cell efficiency. A comparison of the multilayers to ordinary bulk films is made using optical spectroscopy. The optical band gaps for these nanoscale layered films is determined as a function of their modulation wavelengths and compared to theoretical predictions. * This work was supported by the Southeastern University Research Association in collaboration with Oak Ridge National Laboratory and the Florida Solar Energy Center.

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

    PubMed

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

    2013-03-01

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

  19. Testing to Transition the J-2X from Paper to Hardware

    NASA Technical Reports Server (NTRS)

    Byrd, Tom

    2010-01-01

    The J-2X Upper Stage Engine (USE) will be the first new human-rated upper stage engine since the Apollo program of the 1960s. It is designed to carry the Ares I and Ares V into orbit and send the Ares V to the Moon as part of NASA's Constellation Program. This paper will provide an overview of progress on the design, testing, and manufacturing of this new engine in 2009 and 2010. The J-2X embodies the program goals of basing the design on proven technology and experience and seeking commonality between the Ares vehicles as a way to minimize risk, shorten development times, and live within current budget constraints. It is based on the proven J-2 engine used on the Saturn IB and Saturn V launch vehicles. The prime contractor for the J-2X is Pratt & Whitney Rocketdyne (PWR), which is under a design, development, test, and engineering (DDT&E) contract covering the period from June 2006 through September 2014. For Ares I, the J-2X will provide engine start at approximately 190,000 feet, operate roughly 500 seconds, and shut down. For Ares V, the J-2X will start at roughly 190,000 feet to place the Earth departure stage (EDS) in orbit, shut down and loiter for up to five days, re-start on command and operate for roughly 300 seconds at its secondary power level to perform trans lunar injection (TLI), followed by final engine shutdown. The J-2X development effort focuses on four key areas: early risk mitigation, design risk mitigation, component and subassembly testing, and engine system testing. Following that plan, the J-2X successfully completed its critical design review (CDR) in 2008, and it has made significant progress in 2009 and 2010 in moving from the drawing board to the machine shop and test stand. Post-CDR manufacturing is well under way, including PWR in-house and vendor hardware. In addition, a wide range of component and sub-component tests have been completed, and more component tests are planned. Testing includes heritage powerpack, turbopump inducer

  20. Stripe order in La2-xBaxCuO4 in high magnetic fields

    NASA Astrophysics Data System (ADS)

    Huecker, M.; von Zimmermann, M.; Xu, Z. J.; Wen, J. S.; Gu, G. D.; Zaliznyak, I. A.; Chung, J.-H.; Choi, E. S.; Tranquada, J. M.

    2012-02-01

    The observation of enhanced spin stripe order in the vortex cores of La2-xSrxCuO4 has been a landmark experiment that revealed the intimate connection between superconductivity and incommensurate antiferromagnetism. Only recently we have observed a corresponding field dependence of the spin and, more importantly, of the charge stripe order in La2-xBaxCuO4. Here we present our recent results from neutron diffraction, x-ray diffraction, and torque measurements in high magnetic fields. These helped us to establish the field versus temperature and doping phase diagrams for spin and charge order, and to further corroborate the stripe model as the more appropriate description than for example spiral and vortex states.

  1. Broken bond symmetry assists stripe pinning in superconducting La2-xSrxCuO4

    NASA Astrophysics Data System (ADS)

    Tranquada, John; Jacobsen, H.; Zaliznyak, I. A.; Huecker, M.; Gu, G. D.; Savici, A. T.; Winn, B.; Chang, S.

    There has been evidence for quite some time for some degree of charge and spin stripe order in La2-xSrxCuO4 (LSCO). This has been a bit surprising as the crystal structure is supposed to lack the anisotropic Cu-O bonds that lead to robust stripe pinning in La2-xBaxCuO4. Using neutron scattering measurements on the HYSPEC instrument at the Spallation Neutron Source, we have discovered evidence for broken bond symmetry and strong associated lattice fluctuations in an LSCO crystal with x = 0 . 07. The broken bond symmetry occurs within the orthorhombic phase. We also observe quasielastic incommensurate spin excitations that coexist with the bulk superconductivity, suggesting some degree of pair-density-wave order in the superconducting state. Work at BNL supported by Office of Basic Energy Sciences, US DOE, under Contract No. DE-SC00112704.

  2. Status on the Verification of Combustion Stability for the J-2X Engine Thrust Chamber Assembly

    NASA Technical Reports Server (NTRS)

    Casiano, Matthew; Hinerman, Tim; Kenny, R. Jeremy; Hulka, Jim; Barnett, Greg; Dodd, Fred; Martin, Tom

    2013-01-01

    Development is underway of the J -2X engine, a liquid oxygen/liquid hydrogen rocket engine for use on the Space Launch System. The Engine E10001 began hot fire testing in June 2011 and testing will continue with subsequent engines. The J -2X engine main combustion chamber contains both acoustic cavities and baffles. These stability aids are intended to dampen the acoustics in the main combustion chamber. Verification of the engine thrust chamber stability is determined primarily by examining experimental data using a dynamic stability rating technique; however, additional requirements were included to guard against any spontaneous instability or rough combustion. Startup and shutdown chug oscillations are also characterized for this engine. This paper details the stability requirements and verification including low and high frequency dynamics, a discussion on sensor selection and sensor port dynamics, and the process developed to assess combustion stability. A status on the stability results is also provided and discussed.

  3. Prediction of intrinsic motivation and sports performance using 2 x 2 achievement goal framework.

    PubMed

    Li, Chiung-Huang; Chi, Likang; Yeh, Suh-Ruu; Guo, Kwei-Bin; Ou, Cheng-Tsung; Kao, Chun-Chieh

    2011-04-01

    The purpose of this study was to examine the influence of 2 x 2 achievement goals on intrinsic motivation and performance in handball. Participants were 164 high school athletes. All completed the 2 x 2 Achievement Goals Questionnaire for Sport and the Intrinsic Motivation subscale of the Sport Motivation Scale; the coach for each team rated his athletes' overall sports performance. Using simultaneous-regression analyses, mastery-approach goals positively predicted both intrinsic motivation and performance in sports, whereas performance-avoidance goals negatively predicted sports performance. These results suggest that athletes who pursue task mastery and improvement of their competence perform well and enjoy their participation. In contrast, those who focus on avoiding normative incompetence perform poorly.

  4. Synthesis of Plasmonic Cu2-x Se@ZnS Core@Shell Nanoparticles.

    PubMed

    Wolf, Andreas; Härtling, Thomas; Hinrichs, Dominik; Dorfs, Dirk

    2016-03-03

    We report the synthesis of plasmonic Cu2-x Se@ZnS core@shell nanoparticles (NPs). We used a shell growth approach, starting from Cu2-x Se NPs that have been shown before to exhibit a localized surface plasmon resonance (LSPR). By careful synthesis planning we avoided cation exchange reactions and received core@shell nanoparticles that, after oxidation under air, exhibit a strong LSPR in the NIR. Interestingly, the crystalline, closed ZnS shell that we grew with variable thickness still allowed a slow oxidation of the core under ambient conditions, while the core was effectively protected from reduction, even in the presence of reducing agents such as borane tert-butyamine complex and diisobutylaluminum hydride, giving rise to a stable particle LSPR, also under strongly reducing conditions.

  5. Multiple Exhaust Nozzle Effects on J-2X Gas Generator Outlet Impedance

    NASA Technical Reports Server (NTRS)

    Kenny, R. Jeremy; Muss, Jeffrey; Hulka, James R.; Casiano, Matthew

    2010-01-01

    The current test setup of the J-2X gas generator system uses a multiple nozzle configuration to exhaust hot gases to drive the propellant supply turbines. Combustion stability assessment of this gas generator design requires knowledge of the impedance effects the multiple nozzle configuration creates on the combustion chamber acoustic modes. Parallel work between NASA and Sierra Engineering is presented, showing two methods used to calculate the effective end impedance resulting from multiple nozzle configurations. The NASA method is a simple estimate of the effective impedance using the long wavelength approximation. Sierra Engineering has developed a more robust numerical integration method implemented in ROCCID to accommodate for multiple nozzles. Analysis using both methods are compared to J-2X gas generator test data collected over the past year.

  6. Complex spin glass behavior in Ga2-xFexO3

    NASA Astrophysics Data System (ADS)

    Mahana, Sudipta; Topwal, D.

    2017-03-01

    We report the results of the dc magnetization and ac susceptibility measurements on solid solutions of Ga2-xFexO3 (with x = 0.75, 1.0, and 1.25). Magnetic behavior in this series of compounds could broadly be explained by the molecular-field-approximation of a three-sublattice ferrimagnetic model considering three inequivalent octahedral sites. Analysis of frequency dispersion of ac susceptibility reveals a transition from the cluster-glass-like phase to the spin-glass-like phase with decreasing temperature for the x = 0.75 composition. Mentioned glassy behavior is found to gradually evolve with the composition (x) from the Ising type character to Heisenberg type behavior to unconventional glassy behavior for the x = 1.25 composition. Ga2-xFexO3 can hence serve as an ideal system for modeling complex spin glasses.

  7. Duloxetine Inhibits Microglial P2X4 Receptor Function and Alleviates Neuropathic Pain after Peripheral Nerve Injury

    PubMed Central

    Yamashita, Tomohiro; Yamamoto, Shota; Zhang, Jiaming; Kometani, Miho; Tomiyama, Daisuke; Kohno, Keita; Tozaki-Saitoh, Hidetoshi; Inoue, Kazuhide; Tsuda, Makoto

    2016-01-01

    P2X4 receptors (P2X4R) are a family of ATP-gated non-selective cation channels. We previously demonstrated that activation of P2X4R in spinal microglia is crucial for neuropathic pain, a highly debilitating chronic pain condition, suggesting that P2X4R is a potential therapeutic target for treating neuropathic pain. Thus, the identification of a compound that has a potent inhibitory effect on P2X4R is an important clinical challenge. In the present study, we screened a chemical library of clinically approved drugs and show for the first time that duloxetine, a serotonin and noradrenaline reuptake inhibitor, has an inhibitory effect on rodent and human P2X4R. In primary cultured microglial cells, duloxetine also inhibited P2X4R-, but not P2X7R-, mediated responses. Moreover, intrathecal administration of duloxetine in a model of neuropathic pain produced a reversal of nerve injury-induced mechanical allodynia, a cardinal symptom of neuropathic pain. In rats that were pretreated with a serotonin-depleting agent and a noradrenaline neurotoxin, the antiallodynic effect of duloxetine was reduced, but still remained. Based on these results, we suggest that, in addition to duloxetine’s primary inhibitory action on serotonin and noradrenaline transporters, an inhibitory effect on P2X4R may be involved at least in part in an antiallodynic effect of intrathecal duloxetine in a model of neuropathic pain. PMID:27768754

  8. Stable, synthetic analogs of diadenosine tetraphosphate inhibit rat and human P2X3 receptors and inflammatory pain

    PubMed Central

    Viatchenko-Karpinski, Viacheslav; Novosolova, Natalia; Ishchenko, Yevheniia; Azhar, M Ameruddin; Wright, Michael; Tsintsadze, Vera; Kamal, Ahmed; Burnashev, Nail; Voitenko, Nana; Giniatullin, Rashid; Lozovaya, Natalia

    2016-01-01

    Background A growing body of evidence suggests that ATP-gated P2X3 receptors (P2X3Rs) are implicated in chronic pain. We address the possibility that stable, synthetic analogs of diadenosine tetraphosphate (Ap4A) might induce antinociceptive effects by inhibiting P2X3Rs in peripheral sensory neurons. Results The effects of two stable, synthetic Ap4A analogs (AppNHppA and AppCH2ppA) are studied firstly in vitro on HEK293 cells expressing recombinant rat P2XRs (P2X2Rs, P2X3Rs, P2X4Rs, and P2X7Rs) and then using native rat brain cells (cultured trigeminal, nodose, or dorsal root ganglion neurons). Thereafter, the action of these stable, synthetic Ap4A analogs on inflammatory pain and thermal hyperalgesia is studied through the measurement of antinociceptive effects in formalin and Hargreaves plantar tests in rats in vivo. In vitro inhibition of rat P2X3Rs (not P2X2Rs, P2X4Rs nor P2X7Rs) is shown to take place mediated by high-affinity desensitization (at low concentrations; IC50 values 100–250 nM) giving way to only weak partial agonism at much higher concentrations (EC50 values ≥ 10 µM). Similar inhibitory activity is observed with human recombinant P2X3Rs. The inhibitory effects of AppNHppA on nodose, dorsal root, and trigeminal neuron whole cell currents suggest that stable, synthetic Ap4A analogs inhibit homomeric P2X3Rs in preference to heteromeric P2X2/3Rs. Both Ap4A analogs mediate clear inhibition of pain responses in both in vivo inflammation models. Conclusions Stable, synthetic Ap4A analogs (AppNHppA and AppCH2ppA) being weak partial agonist provoke potent high-affinity desensitization-mediated inhibition of homomeric P2X3Rs at low concentrations. Therefore, both analogs demonstrate clear potential as potent analgesic agents for use in the management of chronic pain associated with heightened P2X3R activation. PMID:27030723

  9. ATP-P2X7 Receptor Modulates Axon Initial Segment Composition and Function in Physiological Conditions and Brain Injury.

    PubMed

    Del Puerto, Ana; Fronzaroli-Molinieres, Laure; Perez-Alvarez, María José; Giraud, Pierre; Carlier, Edmond; Wandosell, Francisco; Debanne, Dominique; Garrido, Juan José

    2015-08-01

    Axon properties, including action potential initiation and modulation, depend on both AIS integrity and the regulation of ion channel expression in the AIS. Alteration of the axon initial segment (AIS) has been implicated in neurodegenerative, psychiatric, and brain trauma diseases, thus identification of the physiological mechanisms that regulate the AIS is required to understand and circumvent AIS alterations in pathological conditions. Here, we show that the purinergic P2X7 receptor and its agonist, adenosine triphosphate (ATP), modulate both structural proteins and ion channel density at the AIS in cultured neurons and brain slices. In cultured hippocampal neurons, an increment of extracellular ATP concentration or P2X7-green fluorescent protein (GFP) expression reduced the density of ankyrin G and voltage-gated sodium channels at the AIS. This effect is mediated by P2X7-regulated calcium influx and calpain activation, and impaired by P2X7 inhibition with Brilliant Blue G (BBG), or P2X7 suppression. Electrophysiological studies in brain slices showed that P2X7-GFP transfection decreased both sodium current amplitude and intrinsic neuronal excitability, while P2X7 inhibition had the opposite effect. Finally, inhibition of P2X7 with BBG prevented AIS disruption after ischemia/reperfusion in rats. In conclusion, our study demonstrates an involvement of P2X7 receptors in the regulation of AIS mediated neuronal excitability in physiological and pathological conditions.

  10. Hyperfine specific heats of PrX 2 ( X = Ir, Pt, Rh, Ru) laves phase compounds

    NASA Astrophysics Data System (ADS)

    Greidanus, F. J. A. M.; de Jongh, L. J.; Huiskamp, W. J.; Buschow, K. H. J.

    1980-01-01

    Specific heat data below 1 K for the C-15 compounds PrX 2 (X = Ir, Pt, Rh, Ru) reveal Schottky-type anomalies, ascribed to hyperfine interactions. Apparently the 4f-moments are magnetically ordered. The values deduced for these moments are only ≈ 70% of that for J = 4, indicating that the Pr 3+ moment is partially quenched by the crystal field.

  11. HOSS.edu2.x (Hybrid Optimization Software Suite - Educational Version, Second Generation)

    SciTech Connect

    Rougier, Esteban; Knight, Earl E; Lei, Zhou; Munjiza, Antonio

    2016-07-01

    The hybrid optimization software suite educational version (HOSS.edu2.x) is a general purpose combined finite discrete element (FDEM) code that can be used to simulate problems involving fracture and fragmentation processes, large deformation and large rotations, discrete particle systems, solid-fluid interaction in hydrofracture problems, etc. As such, the code will allow the users to run numerical models in parallel, but with limitations regarding the maximum number of processors and the maximum numbers of elements available.

  12. Mechanism of ivermectin facilitation of human P2X4 receptor channels.

    PubMed

    Priel, Avi; Silberberg, Shai D

    2004-03-01

    Ivermectin (IVM), a widely used antiparasitic agent in human and veterinary medicine, was recently shown to augment macroscopic currents through rat P2X(4) receptor channels. In the present study, the effects of IVM on the human P2X(4) (hP2X(4)) receptor channel stably transfected in HEK293 cells were investigated by recording membrane currents using the patch clamp technique. In whole-cell recordings, IVM (< or =10 microM) applied from outside the cell (but not from inside) increased the maximum current activated by ATP, and slowed the rate of current deactivation. These two phenomena likely result from the binding of IVM to separate sites. A higher affinity site (EC(50) 0.25 microM) increased the maximal current activated by saturating concentrations of ATP without significantly changing the rate of current deactivation or the EC(50) and Hill slope of the ATP concentration-response relationship. A lower affinity site (EC(50) 2 microM) slowed the rate of current deactivation, and increased the apparent affinity for ATP. In cell-attached patch recordings, P2X(4) receptor channels exhibited complex kinetics, with multiple components in both the open and shut distributions. IVM (0.3 microM) increased the number of openings per burst, without significantly changing the mean open or mean shut time within a burst. At higher concentrations (1.5 microM) of IVM, two additional open time components of long duration were observed that gave rise to long-lasting bursts of channel activity. Together, the results suggest that the binding of IVM to the higher affinity site increases current amplitude by reducing channel desensitization, whereas the binding of IVM to the lower affinity site slows the deactivation of the current predominantly by stabilizing the open conformation of the channel.

  13. Sustained calcium entry through P2X nucleotide receptor channels in human airway epithelial cells.

    PubMed

    Zsembery, Akos; Boyce, Amanda T; Liang, Lihua; Peti-Peterdi, János; Bell, P Darwin; Schwiebert, Erik M

    2003-04-11

    Purinergic receptor stimulation has potential therapeutic effects for cystic fibrosis (CF). Thus, we explored roles for P2Y and P2X receptors in stably increasing [Ca(2+)](i) in human CF (IB3-1) and non-CF (16HBE14o(-)) airway epithelial cells. Cytosolic Ca(2+) was measured by fluorospectrometry using the fluorescent dye Fura-2/AM. Expression of P2X receptor (P2XR) subtypes was assessed by immunoblotting and biotinylation. In IB3-1 cells, ATP and other P2Y agonists caused only a transient increase in [Ca(2+)](i) derived from intracellular stores in a Na(+)-rich environment. In contrast, ATP induced an increase in [Ca(2+)](i) that had transient and sustained components in a Na(+)-free medium; the sustained plateau was potentiated by zinc or increasing extracellular pH. Benzoyl-benzoyl-ATP, a P2XR-selective agonist, increased [Ca(2+)](i) only in Na(+)-free medium, suggesting competition between Na(+) and Ca(2+) through P2XRs. Biochemical evidence showed that the P2X(4) receptor is the major subtype shared by these airway epithelial cells. A role for store-operated Ca(2+) channels, voltage-dependent Ca(2+) channels, or Na(+)/Ca(2+) exchanger in the ATP-induced sustained Ca(2+) signal was ruled out. In conclusion, these data show that epithelial P2X(4) receptors serve as ATP-gated calcium entry channels that induce a sustained increase in [Ca(2+)](i). In airway epithelia, a P2XR-mediated Ca(2+) signal may have therapeutic benefit for CF.

  14. Magnetism-driven ferroelectricity in spin-1/2 X Y chains

    NASA Astrophysics Data System (ADS)

    Menchyshyn, Oleg; Ohanyan, Vadim; Verkholyak, Taras; Krokhmalskii, Taras; Derzhko, Oleg

    2015-11-01

    We illustrate the magnetoelectric effect conditioned by the Katsura-Nagaosa-Balatsky (KNB) mechanism within the frames of exactly solvable spin-1 /2 X Y chains. Due to three-spin interactions which are present in our consideration, the magnetization (polarization) is influenced by the electric (magnetic) field even in the absence of the magnetic (electric) field. We also discuss a magnetoelectrocaloric effect examining the entropy changes under the isothermal varying of the magnetic and/or electric field.

  15. Device Performance

    SciTech Connect

    Not Available

    2006-06-01

    In the Device Performance group, within the National Center for Photovoltaic's Measurements and Characterization Division, we measure the performance of PV cells and modules with respect to standard reporting conditions--defined as a reference temperature (25 C), total irradiance (1000 Wm-2), and spectral irradiance distribution (IEC standard 60904-3). Typically, these are ''global'' reference conditions, but we can measure with respect to any reference set. To determine device performance, we conduct two general categories of measurements: spectral responsivity (SR) and current versus voltage (I-V). We usually perform these measurements using standard procedures, but we develop new procedures when required by new technologies. We also serve as an independent facility for verifying device performance for the entire PV community. We help the PV community solve its special measurement problems, giving advice on solar simulation, instrumentation for I-V measurements, reference cells, measurement procedures, and anomalous results. And we collaborate with researchers to analyze devices and materials.

  16. ATP P2X receptors downregulate AMPA receptor trafficking and postsynaptic efficacy in hippocampal neurons.

    PubMed

    Pougnet, Johan-Till; Toulme, Estelle; Martinez, Audrey; Choquet, Daniel; Hosy, Eric; Boué-Grabot, Eric

    2014-07-16

    P2X receptors (P2XRs) are ATP-gated cation channels widely expressed in the brain where they mediate action of extracellular ATP released by neurons or glia. Although purinergic signaling has multiple effects on synaptic transmission and plasticity, P2XR function at brain synapses remains to be established. Here, we show that activation of postsynaptic P2XRs by exogenous ATP or noradrenaline-dependent glial release of endogenous ATP decreases the amplitude of miniature excitatory postsynaptic currents and AMPA-evoked currents in cultured hippocampal neurons. We also observed a P2X-mediated depression of field potentials recorded in CA1 region from brain slices. P2X2Rs trigger dynamin-dependent internalization of AMPA receptors (AMPARs), leading to reduced surface AMPARs in dendrites and at synapses. AMPAR alteration required calcium influx through opened ATP-gated channels and phosphatase or CamKII activities. These findings indicate that postsynaptic P2XRs play a critical role in regulating the surface expression of AMPARs and thereby regulate the synaptic strength.

  17. Cleavage sites in the polypeptide precursors of poliovirus protein P2-X

    SciTech Connect

    Selmer, B.L.; Hanecak, R.; Anderson, C.W.; Wimmer, E.

    1981-01-01

    Partial amino-terminal sequence analysis has been performed on the three major polypeptide products (P2-3b, P2-5b, and P2-X) from the central region (P2) of the poliovirus polyprotein, and this analysis precisely locates the amino termini of these products with respect to the nucleotide sequence of the poliovirus RNA genome. Like most of the products of the replicase region (P3), the amino termini of P2-5b and P2-X are generated by cleavage between glutamine and glycine residues. Thus, P2-5b and P2-X are probably both produced by the action of a singly (virus-encoded.) proteinase. The amino terminus of P2-3b, on the other hand, is produced by a cleavage between the carboxy-terminal tyrosine of VP1 and the glycine encoded by nucleotides 3381-3383. This result may suggest that more than one proteolytic activity is required for the complete processing of the poliovirus polyprotein.

  18. Tuneable Magnetic Phase Transitions in Layered CeMn2Ge2-xSix Compounds

    PubMed Central

    Md Din, M. F.; Wang, J. L.; Cheng, Z. X.; Dou, S. X.; Kennedy, S. J.; Avdeev, M.; Campbell, S. J.

    2015-01-01

    The structural and magnetic properties of seven CeMn2Ge2-xSix compounds with x = 0.0–2.0 have been investigated in detail. Substitution of Ge with Si leads to a monotonic decrease of both a and c along with concomitant contraction of the unit cell volume and significant modifications of the magnetic states - a crossover from ferromagnetism at room temperature for Ge-rich compounds to antiferromagnetism for Si-rich compounds. The magnetic phase diagram has been constructed over the full range of CeMn2Ge2-xSix compositions and co-existence of ferromagnetism and antiferromagnetism has been observed in CeMn2Ge1.2Si0.8, CeMn2Ge1.0Si1.0 and CeMn2Ge0.8Si1.2 with novel insight provided by high resolution neutron and X-ray synchrotron radiation studies. CeMn2Ge2-xSix compounds (x = 0, 0.4 and 0.8) exhibit moderate isothermal magnetic entropy accompanied with a second-order phase transition around room temperature. Analysis of critical behaviour in the vicinity of TCinter for CeMn2Ge2 compound indicates behaviour consistent with three-dimensional Heisenberg model predictions. PMID:26090940

  19. Synthesis of Ultrathin and Thickness-Controlled Cu2-xSe Nanosheets via Cation Exchange.

    PubMed

    Wang, Yuanxing; Zhukovskyi, Maksym; Tongying, Pornthip; Tian, Yang; Kuno, Masaru

    2014-11-06

    We demonstrate the use of cation exchange to synthesize ultrathin and thickness-controlled Cu2-xSe nanosheets (NSs) beginning with CdSe NSs. In this manner, extremely thin (i.e., 1.6 nm thickness) Cu2-xSe NSs, beyond which can be made directly, have been obtained. Furthermore, they represent the thinnest NSs produced via cation exchange. Notably, the exchange reaction preserves the starting morphology of the CdSe sheets and also retains their cubic crystal structure. The resulting nonstoichiometric and cubic Cu2-xSe NSs are stable and do not exhibit any signs of Cu or Se oxidation after exposure to air for 2 weeks. Resulting NSs also show the existence of a localized surface plasmon resonance in the infrared due to the presence of copper vacancies. Efforts to isolate intermediates during the cation exchange reaction show that it occurs via a mechanism where entire sheets are rapidly converted into the final product once the exchange reaction commences, precluding the isolation of alloyed species.

  20. Phonon probe of local strains in SnSxSe2-x mixed crystals

    NASA Astrophysics Data System (ADS)

    Hadjiev, V. G.; De, D.; Peng, H. B.; Manongdo, J.; Guloy, A. M.

    2013-03-01

    We present a combined Raman spectroscopy and density functional perturbation theory (DFPT) study of phonon variation with composition x in the mixed crystals SnSxSe2-x. The experimentally observed two-mode behavior of the A1g and Eg vibrations involving Se(S) atoms is shown to arise from the lack of overlapping of the corresponding phonon dispersion bands in SnS2 and SnSe2. This offers a unique opportunity to assess local distortions of the trigonal Sn3Se pyramids in SnSxSe2-x as no Se and S mode mixing is involved. The dependence of local height and base length of Sn3Se pyramids with x is derived by a procedure that uses the measured A1g (Se) and Eg (Se) phonons in SnSxSe2-x, those calculated by DFPT for SnSe2 at different hydrostatic pressure, DFPT phonon dispersion, and the contribution from mass-disorder induced phonon self-energy.

  1. Charge distribution and oxygen diffusion in hyperstoichiometric uranium dioxide UO2+x (x≤0.25)

    SciTech Connect

    Skomurski, Frances N.; Wang, Jianwei; Ewing, Rodney C.; Becker, U.

    2013-03-03

    Quantum-mechanical techniques were used to determine the charge distribution of uranium atoms in UO2+x (x ≤ 0.25) and to calculate activation-energy barriers to oxygen diffusion. Upon optimization, the reduction in unit-cell volume relative to UO2, and the shortest and bond-lengths (0.22 and 0.24 nm, respectively) are in good agreement with experimental data. The addition of interstitial oxygen to the unoccupied cubic sites in the UO2 structure deflects two nearest-neighbor oxygen atoms along the body diagonal of uranium-occupied cubic sites, creating lattice oxygen defects. In (1×1×2) supercells, the partial oxidation of two U4+ atoms is observed for every interstitial oxygen added to the structure, consistent with previous quantum-mechanical studies. Results favor the stabilization of two U5+ over one U6+ in UO2+x. Calculated activation energies (2.06-2.73 eV) and diffusion rates for oxygen in UO2+x support the idea that defect clusters likely play an increasingly important role as oxidation proceeds.

  2. Average structure and local configuration of excess oxygen in UO2+x

    PubMed Central

    Wang, Jianwei; Ewing, Rodney C.; Becker, Udo

    2014-01-01

    Determination of the local configuration of interacting defects in a crystalline, periodic solid is problematic because defects typically do not have a long-range periodicity. Uranium dioxide, the primary fuel for fission reactors, exists in hyperstoichiometric form, UO2+x. Those excess oxygen atoms occur as interstitial defects, and these defects are not random but rather partially ordered. The widely-accepted model to date, the Willis cluster based on neutron diffraction, cannot be reconciled with the first-principles molecular dynamics simulations present here. We demonstrate that the Willis cluster is a fair representation of the numerical ratio of different interstitial O atoms; however, the model does not represent the actual local configuration. The simulations show that the average structure of UO2+x involves a combination of defect structures including split di-interstitial, di-interstitial, mono-interstitial, and the Willis cluster, and the latter is a transition state that provides for the fast diffusion of the defect cluster. The results provide new insights in differentiating the average structure from the local configuration of defects in a solid and the transport properties of UO2+x. PMID:24642875

  3. The Cellular Prion Protein Prevents Copper-Induced Inhibition of P2X4 Receptors

    PubMed Central

    Lorca, Ramón A.; Varela-Nallar, Lorena; Inestrosa, Nibaldo C.; Huidobro-Toro, J. Pablo

    2011-01-01

    Although the physiological function of the cellular prion protein (PrPC) remains unknown, several evidences support the notion of its role in copper homeostasis. PrPC binds Cu2+ through a domain composed by four to five repeats of eight amino acids. Previously, we have shown that the perfusion of this domain prevents and reverses the inhibition by Cu2+ of the adenosine triphosphate (ATP)-evoked currents in the P2X4 receptor subtype, highlighting a modulatory role for PrPC in synaptic transmission through regulation of Cu2+ levels. Here, we study the effect of full-length PrPC in Cu2+ inhibition of P2X4 receptor when both are coexpressed. PrPC expression does not significantly change the ATP concentration-response curve in oocytes expressing P2X4 receptors. However, the presence of PrPC reduces the inhibition by Cu2+ of the ATP-elicited currents in these oocytes, confirming our previous observations with the Cu2+ binding domain. Thus, our observations suggest a role for PrPC in modulating synaptic activity through binding of extracellular Cu2+. PMID:22114745

  4. Physical basis of apparent pore-dilation of ATP-activated P2X receptor channels

    PubMed Central

    Li, Mufeng; Toombes, Gilman E S; Silberberg, Shai D; Swartz, Kenton J

    2016-01-01

    The selectivity of ion channels is fundamental for their roles in electrical and chemical signaling, and ion homeostasis. Although most ion channels exhibit stable ion selectivity, the prevailing view for purinergic P2X receptor channels, transient receptor potential V1 (TRPV1) channels and acid sensing ion channels (ASICs) is that their ion conduction pores dilate upon prolonged activation. We investigated this mechanism in P2X receptors and found that the hallmark shift in equilibrium potential observed with prolonged channel activation does not result from pore dilation, but from time-dependent alterations in the concentration of intracellular ions. We derived a physical model to calculate ion concentration changes during patch-clamp recordings, which validates our experimental findings and provides a quantitative guideline for effectively controlling ion concentration. Our results have fundamental implications for understanding ion permeation and gating in P2X receptor channels, and more broadly for using patch-clamp techniques to study ion channels and neuronal excitability. PMID:26389841

  5. Characterization of spin dynamics in stripe-ordered La2-xSrxNiO4

    NASA Astrophysics Data System (ADS)

    Woo, H.; Tranquada, J. M.; Boothroyd, A. T.; Nakajima, K.; Perring, T. G.; Frost, C.; Freeman, P. G.; Prabhakaran, D.; Yamada, K.

    2004-03-01

    Inelastic neutron scattering experiments at a spallation source have enabled us to measure the full momentum- and energy- dependent spectra of magnetic fluctuations in the charge- and spin-stripe ordered systems La_2-xSr_xNiO4 ( x=1/3 and x=0.275). Peaks in the dynamic magnetic response at incommensurate wavevectors and over a wide frequency range are commonly observed in the high-Tc superconductors YBa_2Cu_3O_6+x and La_2-xA_xCuO_4(A=Sr,Ba) , as well as in the static charge- and spin-striped system nickelates La_2-xSr_xNiO_4. High energy transfer up to 90meV with broad reciprocal spaces was observed. In addition to intrastripe and interstripe exchange interactions between neighboring Ni spins [1], exchange interactions between diagonal Ni spins (not through oxygen) are also considered. We will present a detailed measurement and analysis in the NiO2 plane. We acknowledge U.S.-DOE for financial support: contract # DE-AC02-98CH1088. [1] Boothroyd et al. Phys. Rev. B 67, 100407(R) (2003).

  6. The Grid Density Dependence of the Unsteady Pressures of the J-2X Turbines

    NASA Technical Reports Server (NTRS)

    Schmauch, Preston B.

    2011-01-01

    The J-2X engine was originally designed for the upper stage of the cancelled Crew Launch Vehicle. Although the Crew Launch Vehicle was cancelled the J-2X engine, which is currently undergoing hot-fire testing, may be used on future programs. The J-2X engine is a direct descendent of the J-2 engine which powered the upper stage during the Apollo program. Many changes including a thrust increase from 230K to 294K lbf have been implemented in this engine. As part of the design requirements, the turbine blades must meet minimum high cycle fatigue factors of safety for various vibrational modes that have resonant frequencies in the engine's operating range. The unsteady blade loading is calculated directly from CFD simulations. A grid density study was performed to understand the sensitivity of the spatial loading and the magnitude of the on blade loading due to changes in grid density. Given that the unsteady blade loading has a first order effect on the high cycle fatigue factors of safety, it is important to understand the level of convergence when applying the unsteady loads. The convergence of the unsteady pressures of several grid densities will be presented for various frequencies in the engine's operating range.

  7. Sub-Scale Testing and Development of the J-2X Fuel Turbopump Inducer

    NASA Technical Reports Server (NTRS)

    Sargent, Scott R.; Becht, David G.

    2011-01-01

    In the early stages of the J-2X upper stage engine program, various inducer configurations proposed for use in the fuel turbopump (FTP) were tested in water. The primary objectives of this test effort were twofold. First, to obtain a more comprehensive data set than that which existed in the Pratt & Whitney Rocketdyne (PWR) historical archives from the original J-2S program, and second, to supplement that data set with information regarding the cavitation induced vibrations for both the historical J-2S configuration as well as those tested for the J-2X program. The J-2X FTP inducer, which actually consists of an inducer stage mechanically attached to a kicker stage, underwent 4 primary iterations utilizing sub-scaled test articles manufactured and tested in PWR's Engineering Development Laboratory (EDL). The kicker remained unchanged throughout the test series. The four inducer configurations tested retained many of the basic design features of the J-2S inducer, but also included variations on leading edge blade thickness and blade angle distribution, primarily aimed at improving suction performance at higher flow coefficients. From these data sets, the effects of the tested design variables on hydrodynamic performance and cavitation instabilities were discerned. A limited comparison of impact to the inducer efficiency was determined as well.

  8. Device Demonstration

    DTIC Science & Technology

    2006-12-31

    effecting change in the electrical properties of the material. Due to the heating requirement in setting the state, stray radiation does not affect the...device as in traditional binary RAM, thus giving the device radiation-hard properties . Uniformity of the heater elements at a small size below 100 nm is...Molybdenum was chosen for the cathode tube material because it has a low sputtering coefficient, and it’s high temperature properties .. The tubes are

  9. NASA's J-2X Engine Builds on the Apollo Program for Lunar Return Missions

    NASA Technical Reports Server (NTRS)

    Snoddy, Jimmy R.

    2006-01-01

    In January 2006, NASA streamlined its U.S. Vision for Space Exploration hardware development approach for replacing the Space Shuttle after it is retired in 2010. The revised CLV upper stage will use the J-2X engine, a derivative of NASA s Apollo Program Saturn V s S-II and S-IVB main propulsion, which will also serve as the Earth Departure Stage (EDS) engine. This paper gives details of how the J- 2X engine effort mitigates risk by building on the Apollo Program and other lessons learned to deliver a human-rated engine that is on an aggressive development schedule, with first demonstration flight in 2010 and human test flights in 2012. It is well documented that propulsion is historically a high-risk area. NASA s risk reduction strategy for the J-2X engine design, development, test, and evaluation is to build upon heritage hardware and apply valuable experience gained from past development efforts. In addition, NASA and its industry partner, Rocketdyne, which originally built the J-2, have tapped into their extensive databases and are applying lessons conveyed firsthand by Apollo-era veterans of America s first round of Moon missions in the 1960s and 1970s. NASA s development approach for the J-2X engine includes early requirements definition and management; designing-in lessons learned from the 5-2 heritage programs; initiating long-lead procurement items before Preliminary Desi& Review; incorporating design features for anticipated EDS requirements; identifying facilities for sea-level and altitude testing; and starting ground support equipment and logistics planning at an early stage. Other risk reduction strategies include utilizing a proven gas generator cycle with recent development experience; utilizing existing turbomachinery ; applying current and recent main combustion chamber (Integrated Powerhead Demonstrator) and channel wall nozzle (COBRA) advances; and performing rigorous development, qualification, and certification testing of the engine system

  10. Heat Shock Protein 90 Inhibitors Reduce Trafficking of ATP-gated P2X1 Receptors and Human Platelet Responsiveness*

    PubMed Central

    Lalo, Ulyana; Jones, Sarah; Roberts, Jonathan A.; Mahaut-Smith, Martyn P.; Evans, Richard J.

    2012-01-01

    We have used selective inhibitors to determine whether the molecular chaperone heat shock protein 90 (HSP90) has an effect on both recombinant and native human P2X1 receptors. P2X1 receptor currents in HEK293 cells were reduced by ∼70–85% by the selective HSP90 inhibitor geldanamycin (2 μm, 20 min). This was associated with a speeding in the time course of desensitization as well as a reduction in cell surface expression. Imaging in real time of photoactivatable GFP-tagged P2X receptors showed that they are highly mobile. Geldanamycin almost abolished this movement for P2X1 receptors but had no effect on P2X2 receptor trafficking. P2X1/2 receptor chimeras showed that the intracellular N and C termini were involved in geldanamycin sensitivity. Geldanamycin also inhibited native P2X1 receptor-mediated responses. Platelet P2X1 receptors play an important role in hemostasis, contribute to amplification of signaling to a range of stimuli including collagen, and are novel targets for antithrombotic therapies. Platelet P2X1 receptor-, but not P2Y1 receptor-, mediated increases in intracellular calcium were reduced by 40–45% following HSP90 inhibition with geldanamycin or radicicol. Collagen stimulation leads to ATP release from platelets, and calcium increases to low doses of collagen were also reduced by ∼40% by the HSP90 inhibitors consistent with an effect on P2X1 receptors. These studies suggest that HSP90 inhibitors may be as effective as selective antagonists in regulating platelet P2X1 receptors, and their potential effects on hemostasis should be considered in clinical studies. PMID:22851178

  11. Postsynaptic P2X3-containing receptors in gustatory nerve fibres mediate responses to all taste qualities in mice.

    PubMed

    Vandenbeuch, Aurelie; Larson, Eric D; Anderson, Catherine B; Smith, Steven A; Ford, Anthony P; Finger, Thomas E; Kinnamon, Sue C

    2015-03-01

    Taste buds release ATP to activate ionotropic purinoceptors composed of P2X2 and P2X3 subunits, present on the taste nerves. Mice with genetic deletion of P2X2 and P2X3 receptors (double knockout mice) lack responses to all taste stimuli presumably due to the absence of ATP-gated receptors on the afferent nerves. Recent experiments on the double knockout mice showed, however, that their taste buds fail to release ATP, suggesting the possibility of pleiotropic deficits in these global knockouts. To test further the role of postsynaptic P2X receptors in afferent signalling, we used AF-353, a selective antagonist of P2X3-containing receptors to inhibit the receptors acutely during taste nerve recording and behaviour. The specificity of AF-353 for P2X3-containing receptors was tested by recording Ca(2+) transients to exogenously applied ATP in fura-2 loaded isolated geniculate ganglion neurons from wild-type and P2X3 knockout mice. ATP responses were completely inhibited by 10 μm or 100 μm AF-353, but neither concentration blocked responses in P2X3 single knockout mice wherein the ganglion cells express only P2X2-containing receptors. Furthermore, AF-353 had no effect on taste-evoked ATP release from taste buds. In wild-type mice, i.p. injection of AF-353 or simple application of the drug directly to the tongue, inhibited taste nerve responses to all taste qualities in a dose-dependent fashion. A brief access behavioural assay confirmed the electrophysiological results and showed that preference for a synthetic sweetener, SC-45647, was abolished following i.p. injection of AF-353. These data indicate that activation of P2X3-containing receptors is required for transmission of all taste qualities.

  12. Modulation of Mouse Embryonic Stem Cell Proliferation and Neural Differentiation by the P2X7 Receptor

    PubMed Central

    Glaser, Talita; de Oliveira, Sophia La Banca; Cheffer, Arquimedes; Beco, Renata; Martins, Patrícia; Fornazari, Maynara; Lameu, Claudiana; Junior, Helio Miranda Costa; Coutinho-Silva, Robson; Ulrich, Henning

    2014-01-01

    Background Novel developmental functions have been attributed to the P2X7 receptor (P2X7R) including proliferation stimulation and neural differentiation. Mouse embryonic stem cells (ESC), induced with retinoic acid to neural differentiation, closely assemble processes occurring during neuroectodermal development of the early embryo. Principal Findings P2X7R expression together with the pluripotency marker Oct-4 was highest in undifferentiated ESC. In undifferentiated cells, the P2X7R agonist Bz-ATP accelerated cell cycle entry, which was blocked by the specific P2X7R inhibitor KN-62. ESC induced to neural differentiation with retinoic acid, reduced Oct-4 and P2X7R expression. P2X7R receptor-promoted intracellular calcium fluxes were obtained at lower Bz-ATP ligand concentrations in undifferentiated and in neural-differentiated cells compared to other studies. The presence of KN-62 led to increased number of cells expressing SSEA-1, Dcx and β3-tubulin, as well as the number of SSEA-1 and β3-tubulin-double-positive cells confirming that onset of neuroectodermal differentiation and neuronal fate determination depends on suppression of P2X7R activity. Moreover, an increase in the number of Ki-67 positive cells in conditions of P2X7R inhibition indicates rescue of progenitors into the cell cycle, augmenting the number of neuroblasts and consequently neurogenesis. Conclusions In embryonic cells, P2X7R expression and activity is upregulated, maintaining proliferation, while upon induction to neural differentiation P2X7 receptor expression and activity needs to be suppressed. PMID:24798220

  13. Effect of P2X4R on airway inflammation and airway remodeling in allergic airway challenge in mice

    PubMed Central

    CHEN, HONGXIA; XIA, QINGQING; FENG, XIAOQIAN; CAO, FANGYUAN; YU, HANG; SONG, YINLI; NI, XIUQIN

    2016-01-01

    P2X4 receptor (P2X4R) is the most widely expressed subtype of the P2XRs in the purinergic receptor family. Adenosine triphosphate (ATP), a ligand for this receptor, has been implicated in the pathogenesis of asthma. ATP-P2X4R signaling is involved in pulmonary vascular remodeling, and in the proliferation and differentiation of airway and alveolar epithelial cell lines. However, the role of P2X4R in asthma remains to be elucidated. This aim of the present study was to investigate the effects of P2X4R in a murine experimental asthma model. The asthmatic model was established by the inhalation of ovalbumin (OVA) in BALB/c mice. The mice were treated with P2X4R-specific agonists and antagonists to investigate the role of this receptor in vivo. Pathological changes in the bronchi and lung tissues were examined using hematoxylin and eosin staining, Masson's trichrome staining and Alcian blue staining. The inflammatory cells in the bronchoalveolar lavage fluid were counted, and the expression levels of P2X4R, α-smooth muscle actin (α-SMA) and proliferating cell nuclear antigen (PCNA) were detected using western blotting. In the OVA-challenged mice, inflammation, infiltration, collagen deposition, mucus production, and the expression levels of P2X4R and PCNA were all increased; however, the expression of α-SMA was decreased, compared with the mice in the control group. Whereas treatment with the P2X4R agonist, ATP, enhanced the allergic reaction, treatment with the P2X4R antagonist, 5-BDBD, attenuated the allergic reaction. The results suggested that ATP-P2X4R signaling may not only contribute to airway inflammation, but it may also contribute to airway remodeling in allergic asthma in mice. PMID:26648454

  14. Incommensurate Cu/Co Ordering in the TlCo 2- xCu xSe 2 ( x˜1) System

    NASA Astrophysics Data System (ADS)

    Norén, L.; Withers, R. L.; Berger, R.

    2000-05-01

    Cu/Co ordering in TlCo2-xCuxSe2, (x∼1) has been investigated using electron and X-ray powder diffraction. The average structure of the x=1 compound can be indexed on an F-centered orthorhombic cell, a=5.5518(6) Å, b=5.4755(5) Å, and c=13.7387(17) Å. Additional weak satellite reflections characterized by the primary modulation wave vector qi∼0.184a* and indicative of an incommensurate modulated structure are revealed by electron diffraction. Characteristic extinction conditions in conjunction with mmm Laue symmetry and known crystal chemical constraints imply a (3+1)-dimensional superspace group symmetry of Fmmm(α01)00s. The incommensurate modulation is attributed to occupational ordering of the two transition metal atoms and associated structural relaxation. The real space interpretation of the Cu/Co ordering pattern is that copper and cobalt atoms form separate layers in the structure at z={1}/{4} and {3}/{4}, respectively. These layers are periodically interchanged as one moves along the x direction. Two periods of this square-wave-like modulation is close to 11a in length but is non-rational compared with the average structure.

  15. Inflammatory early events associated to the role of P2X7 receptor in acute murine toxoplasmosis.

    PubMed

    Corrêa, Gladys; Almeida Lindenberg, Carolina de; Moreira-Souza, Aline Cristina de Abreu; Savio, Luiz Eduardo Baggio; Takiya, Christina Maeda; Marques-da-Silva, Camila; Vommaro, Rossiane Claudia; Coutinho-Silva, Robson

    2017-04-01

    Activation of the purinergic P2X7 receptor by extracellular ATP (eATP) potentiates proinflammatory responses during infections by intracellular pathogens. Extracellular ATP triggers an antimicrobial response in macrophages infected with Toxoplasma gondii in vitro, suggesting that purinergic signaling may stimulate host defense mechanisms against toxoplasmosis. Here, we provide in vivo evidence in support of this hypothesis, by showing that P2X7(-/-) mice are more susceptible than P2X7(+/+) mice to acute infection by the RH strain of T. gondii, and that this phenomenon is associated with a deficient proinflammatory response. Four days post-infection, peritoneal washes from infected P2X7(-/-) mice had no or little increase in the levels of the proinflammatory cytokines IL-12, IL-1β, IFN-γ, and TNF-α, whose levels increased markedly in samples from infected P2X7(+/+) mice. Infected P2X7(-/-) mice displayed an increase in organ weight and histological alterations in some of the 'shock organs' in toxoplasmosis - the liver, spleen and mesenteric lymph nodes. The liver of infected P2X7(-/-) mice had smaller granulomas, but increased parasite load/granuloma. Our results confirm that the P2X7 receptor is involved in containing T. gondii spread in vivo, by stimulating inflammation.

  16. Purinoreceptor P2X7 Regulation of Ca2+ Mobilization and Cytoskeletal Rearrangement Is Required for Corneal Reepithelialization after Injury

    PubMed Central

    Minns, Martin S.; Teicher, Gregory; Rich, Celeste B.; Trinkaus-Randall, Vickery

    2017-01-01

    The process of wound healing involves a complex network of signaling pathways working to promote rapid cell migration and wound closure. Activation of purinergic receptors by secreted nucleotides plays a major role in calcium mobilization and the subsequent calcium-dependent signaling that is essential for proper healing. The role of the purinergic receptor P2X7 in wound healing is still relatively unknown. We demonstrate that P2X7 expression increases at the leading edge of corneal epithelium after injury in an organ culture model, and that this change occurs despite an overall decrease in P2X7 expression throughout the epithelium. Inhibition of P2X7 prevents this change in localization after injury and impairs wound healing. In cell culture, P2X7 inhibition attenuates the amplitude and duration of injury-induced calcium mobilization in cells at the leading edge. Immunofluorescence analysis of scratch-wounded cells reveals that P2X7 inhibition results in an overall decrease in the number of focal adhesions along with a concentration of focal adhesions at the wound margin. Live cell imaging of green fluorescent protein–labeled actin and talin shows that P2X7 inhibition alters actin cytoskeletal rearrangements and focal adhesion dynamics after injury. Together, these data demonstrate that P2X7 plays a critical role in mediating calcium signaling and coordinating cytoskeletal rearrangement at the leading edge, both of which processes are early signaling events necessary for proper epithelial wound healing. PMID:26683661

  17. Examining Dual Meanings of Items in 2 x 2 Achievement Goal Questionnaires through MTMM Modeling and MDS Approach

    ERIC Educational Resources Information Center

    Wu, Chia-Huei; Chen, Lung Hung

    2010-01-01

    In 2001, Elliot and McGregor proposed a 2 x 2 (mastery-performance x approach- avoidance) achievement goal frameworks and developed a questionnaire to measure four goals (mastery-approach, mastery-avoidance, performance-approach, and performance-avoidance goals). This study examines the dual meanings of items in 2 x 2 achievement goal…

  18. P2X(7) receptor activation enhances SK3 channels- and cystein cathepsin-dependent cancer cells invasiveness.

    PubMed

    Jelassi, B; Chantôme, A; Alcaraz-Pérez, F; Baroja-Mazo, A; Cayuela, M L; Pelegrin, P; Surprenant, A; Roger, S

    2011-05-05

    ATP-gated P2X(7) receptors (P2X(7)R) are unusual plasma membrane ion channels that have been extensively studied in immune cells. More recently, P2X(7)R have been described as potential cancer cell biomarkers. However, mechanistic links between P2X(7)R and cancer cell processes are unknown. Here, we show, in the highly aggressive human breast cancer cell line MDA-MB-435s, that P2X(7) receptor is highly expressed and fully functional. Its activation is responsible for the extension of neurite-like cellular prolongations, of the increase in cell migration by 35% and in cell invasion through extracellular matrix by 150%. The change in cancer cell morphology and the increased migration appeared to be due to the activation of Ca(2+)-activated SK3 potassium channels. The enhanced invasion through the extracellular matrix was related to the increase of mature forms of cysteine cathepsins in the extracellular medium, which was independent of SK3 channel activity and not associated with cell death. Pharmacological targeting of P2X(7)R in vivo was crucial for cell invasiveness in a zebrafish model of metastases. Our results demonstrate a novel mechanistic link between P2X(7)R functionality in cancer cells and invasiveness, a key parameter in tumour growth and in the development of metastases. They also suggest a potential therapeutic role for the newly developed P2X(7)R antagonists.

  19. P2X7 receptor-induced death of motor neurons by a peroxynitrite/FAS-dependent pathway

    PubMed Central

    Gandelman, Mandi; Levy, Mark; Cassina, Patricia; Barbeito, Luis; Beckman, Joseph S

    2013-01-01

    The P2X7 receptor/channel responds to extracellular ATP and is associated with neuronal death and neuroinflammation in spinal cord injury and amyotrophic lateral sclerosis (ALS). Whether activation of P2X7 directly causes motor neuron death is unknown. We found that cultured motor neurons isolated from embryonic rat spinal cord express P2X7 and underwent caspase-dependent apoptosis when exposed to exceptionally low concentrations of the P2X7 agonist 3′-O-(4-benzoyl)-ATP (BzATP). The P2X7 inhibitors BBG, oATP and KN-62 prevented BzATP-induced motor neuron death. The endogenous P2X7 agonist ATP induced motor neuron death at low concentrations (1-100 μM). High concentrations of ATP (1 mM) paradoxically became protective due to degradation in the culture media to produce adenosine and activate adenosine receptors. P2X7-induced motor neuron death was dependent on neuronal nitric oxide synthase-mediated production of peroxynitrite, p38 activation and autocrine FAS signaling. Taken together, our results indicate that motor neurons are highly sensitive to P2X7 activation, which triggers apoptosis by activation of the well-established peroxynitrite/FAS death pathway in motor neurons. PMID:23646980

  20. P2X7 receptor-mediated PARP1 activity regulates astroglial death in the rat hippocampus following status epilepticus

    PubMed Central

    Kim, Ji Yang; Ko, Ah-Reum; Kim, Ji-Eun

    2015-01-01

    Poly(ADP-ribose) polymerase-1 (PARP1) plays a regulatory role in apoptosis, necrosis, and other cellular processes after injury. Recently, we revealed that PARP1 regulates the differential neuronal/astroglial responses to pilocarpine-induced status epilepticus (SE) in the distinct brain regions. In addition, P2X7 receptor (P2X7R), an ATP-gated ion channel, activation accelerates astroglial apoptosis, while it attenuates clasmatodendrosis (lysosome-derived autophagic astroglial death). Therefore, we investigated whether P2X7R regulates regional specific astroglial PARP1 expression/activation in response to SE. In the present study, P2X7R activation exacerbates SE-induced astroglial apoptosis, while P2X7R inhibition attenuates it accompanied by increasing PARP1 activity in the molecular layer of the dentate gyrus following SE. In the CA1 region, however, P2X7R inhibition deteriorates SE-induced clasmatodendrosis via PARP1 activation following SE. Taken together, our findings suggest that P2X7R function may affect SE-induced astroglial death by regulating PARP1 activation/expression in regional-specific manner. Therefore, the selective modulation of P2X7R-mediated PARP1 functions may be a considerable strategy for controls in various types of cell deaths. PMID:26388738

  1. Effect of the purinergic receptor P2X7 on Chlamydia infection in cervical epithelial cells and vaginally infected mice.

    PubMed

    Darville, Toni; Welter-Stahl, Lynn; Cruz, Cristiane; Sater, Ali Abdul; Andrews, Charles W; Ojcius, David M

    2007-09-15

    Ligation of the purinergic receptor, P2X7R, with its agonist ATP has been previously shown to inhibit intracellular infection by chlamydiae and mycobacteria in macrophages. The effect of P2X7R on chlamydial infection had never been investigated in the preferred target cells of chlamydiae, cervical epithelial cells, nor in vaginally infected mice. In this study, we show that treatment of epithelial cells with P2X7R agonists inhibits partially Chlamydia infection in epithelial cells. Chelation of ATP with magnesium or pretreatment with a P2X7R antagonist blocks the inhibitory effects of ATP. Similarly to previous results obtained with macrophages, ATP-mediated inhibition of infection in epithelial cells requires activation of host-cell phospholipase D. Vaginal infection was also more efficient in P2X7R-deficient mice, which also displayed a higher level of acute inflammation in the endocervix, oviduct, and mesosalpingeal tissues than in infected wild-type mice. However, secretion of IL-1beta, which requires P2X7R ligation during infection by other pathogens, was decreased mildly and only at short times of infection. Taken together, these results suggest that P2X7R affects Chlamydia infection by directly inhibiting infection in epithelial cells, rather than through the ability of P2X7R to modulate IL-1beta secretion.

  2. Electrophysiological studies of upregulated P2X7 receptors in rat superior cervical ganglia after myocardial ischemic injury.

    PubMed

    Kong, Fanjun; Liu, Shuangmei; Xu, Changshui; Liu, Jun; Li, Guodong; Li, Guilin; Gao, Yun; Lin, Hong; Tu, Guihua; Peng, Haiying; Qiu, Shuyi; Fan, Bo; Zhu, Qicheng; Yu, Shicheng; Zheng, Chaoran; Liang, Shangdong

    2013-09-01

    Myocardial ischemic injury activates cardiac sympathetic afferent fibers and elicits a sympathoexcitatory reflex by exciting sympathetic efferent action, with resultant augmentation of myocardial oxygen consumption, leading to a vicious cycle of exaggerating myocardial ischemia. P2X7 receptor participates in the neuronal functions and the neurological disorders. This study examined the role of P2X7 receptor of superior cervical ganglia (SCG) in sympathoexcitatory reflex. Our results showed that the expression of P2X7 receptor at both mRNA and protein in SCG was increased after myocardial ischemic injury. P2X7 receptor agonists at the same concentration activated much larger amplitudes of the currents in the SCG neurons of myocardial ischemic rats than those in control rats. P2X7 receptor antagonist (brilliant blue G, BBG) significantly inhibited P2X7 receptor agonist-activated currents in the SCG neurons. Excessive phosphorylation of MAPK ERK1/2 upon the activation of P2X7 receptor might be a mechanism mediating the signal transduction after myocardial ischemic injury. Therefore, the sensitized P2X7 receptor in SCG was involved in the nociceptive transmission of sympathoexcitatory reflex induced by myocardial ischemic injury.

  3. Identification of Human P2X1 Receptor-interacting Proteins Reveals a Role of the Cytoskeleton in Receptor Regulation*

    PubMed Central

    Lalo, Ulyana; Roberts, Jonathan A.; Evans, Richard J.

    2011-01-01

    P2X1 receptors are ATP-gated ion channels expressed by smooth muscle and blood cells. Carboxyl-terminally His-FLAG-tagged human P2X1 receptors were stably expressed in HEK293 cells and co-purified with cytoskeletal proteins including actin. Disruption of the actin cytoskeleton with cytochalasin D inhibited P2X1 receptor currents with no effect on the time course of the response or surface expression of the receptor. Stabilization of the cytoskeleton with jasplakinolide had no effect on P2X1 receptor currents but decreased receptor mobility. P2X2 receptor currents were unaffected by cytochalasin, and P2X1/2 receptor chimeras were used to identify the molecular basis of actin sensitivity. These studies showed that the intracellular amino terminus accounts for the inhibitory effects of cytoskeletal disruption similar to that shown for lipid raft/cholesterol sensitivity. Stabilization of the cytoskeleton with jasplakinolide abolished the inhibitory effects of cholesterol depletion on P2X1 receptor currents, suggesting that lipid rafts may regulate the receptor through stabilization of the cytoskeleton. These studies show that the cytoskeleton plays an important role in P2X1 receptor regulation. PMID:21757694

  4. Inhibition of chlamydial infectious activity due to P2X7R-dependent phospholipase D activation.

    PubMed

    Coutinho-Silva, Robson; Stahl, Lynn; Raymond, Marie-Noëlle; Jungas, Thomas; Verbeke, Philippe; Burnstock, Geoffrey; Darville, Toni; Ojcius, David M

    2003-09-01

    Chlamydia trachomatis survives within host cells by inhibiting fusion between Chlamydia vacuoles and lysosomes. We show here that treatment of infected macrophages with ATP leads to killing of chlamydiae through ligation of the purinergic receptor, P2X(7)R. Chlamydial killing required phospholipase D (PLD) activation, as PLD inhibition led to rescue of chlamydiae in ATP-treated macrophages. However, there was no PLD activation nor chlamydial killing in ATP-treated P2X(7)R-deficient macrophages. P2X(7)R ligation exerts its effects by promoting fusion between Chlamydia vacuoles and lysosomes. P2X(7)R stimulation also resulted in macrophage death, but fusion with lysosomes preceded macrophage death and PLD inhibition did not prevent macrophage death. These results suggest that P2X(7)R ligation leads to PLD activation, which is directly responsible for inhibition of infection.

  5. PLASMA DEVICE

    DOEpatents

    Baker, W.R.; Brathenahl, A.; Furth, H.P.

    1962-04-10

    A device for producing a confined high temperature plasma is described. In the device the concave inner surface of an outer annular electrode is disposed concentrically about and facing the convex outer face of an inner annular electrode across which electrodes a high potential is applied to produce an electric field there between. Means is provided to create a magnetic field perpendicular to the electric field and a gas is supplied at reduced pressure in the area therebetween. Upon application of the high potential, the gas between the electrodes is ionized, heated, and under the influence of the electric and magnetic fields there is produced a rotating annular plasma disk. The ionized plasma has high dielectric constant properties. The device is useful as a fast discharge rate capacitor, in controlled thermonuclear research, and other high temperature gas applications. (AEC)

  6. Electrooptical Devices

    DTIC Science & Technology

    1977-03-31

    LEXINGTON MASSACHUSETTS ABSTRACT The current objectives of the electrooptical device program are: (1) to perform life tests on GalnAsP/lnP double...DH GalnAsP/lnP lasers, operating contin- uously at room temperature, have been placed on life test . The first three devices, fabricated from one...on life tests of DH GalnAsP/lnP lasers. The first three lasers to be put on life test have been in continuous operation at room tempera- ture in an

  7. Involvement of RVM-expressed P2X7 receptor in bone cancer pain: mechanism of descending facilitation.

    PubMed

    Huang, Zhang Xiang; Lu, Zhi Jie; Ma, Wei Qing; Wu, Fei Xiang; Zhang, Yu Qiu; Yu, Wei-Feng; Zhao, Zhi Qi

    2014-04-01

    Patients with bone cancer commonly experience bone pain that is severe, intolerable, and difficult to manage. The rostral ventromedial medulla (RVM) plays an important role in the development of chronic pain via descending facilitation of spinal nociception. The compelling evidence shows that glial P2X7 receptor (P2X7R) is involved in the induction and maintenance of chronic pain syndromes. The present study explored the mechanism of glial activation and P2X7R expression underlying the induction of bone cancer pain. The results demonstrated that microglia and astrocytes in the RVM were markedly activated in bone cancer rats, and the expression of P2X7R was significantly upregulated. Injection of Brilliant Blue G (BBG), an inhibitor of P2X7R, into the RVM significantly alleviated pain behaviors of cancer rats, which was supported by intra-RVM injection of RNA interference targeting the P2X7R in the RVM. It is suggested that activation of microglia-expressed P2X7R in the RVM contributes to bone cancer pain. Given that 5-HT in the RVM is involved in modulating spinal nociception, changes in 5-HT and Fos expression were addressed in the spinal cord. Inhibition of P2X7R by BBG or small-interference RNA targeting P2X7 in the RVM markedly reduced 5-HT level and Fos expression in the spinal cord. The data clearly suggest that the activation of microglial P2X7R in the RVM contributes to the development of bone cancer pain via upregulation of spinal 5HT levels by the descending pain facilitatory system.

  8. Contribution of P2X4 receptors to ethanol intake in male C57BL/6 mice

    PubMed Central

    Wyatt, Letisha R.; Finn, Deborah A.; Khoja, Sheraz; Yardley, Megan M; Asatryan, Liana; Alkana, Ronald L.; Davies, Daryl L.

    2014-01-01

    P2X receptors (P2XRs) are a family of cation-permeable ligand-gated ion channels activated by synaptically released extracellular ATP. The P2X4 subtype is abundantly expressed in the CNS and is sensitive to low intoxicating ethanol concentrations. Genetic meta-analyses identified the p2rx4 gene as a candidate gene for innate alcohol intake and/or preference. The current study used mice lacking the p2rx4 gene (knockout, KO) and wildtype (WT) C57BL/6 controls to test the hypothesis that P2X4Rs contribute to ethanol intake. The early acquisition and early maintenance phases of ethanol intake were measured with three different drinking procedures. Further, we tested the effects of ivermectin (IVM), a drug previously shown to reduce ethanol’s effects on P2X4Rs and to reduce ethanol intake and preference, for its ability to differentially alter stable ethanol intake in KO and WT mice. Depending on the procedure and the concentration of the ethanol solution, ethanol intake was transiently increased in P2X4R KO versus WT mice during the acquisition of 24-hr and limited access ethanol intake. IVM significantly reduced ethanol intake in P2X4R KO and WT mice, but the degree of reduction was 50% less in the P2X4R KO mice. Western blot analysis identified significant changes in -γ aminobutyric acidA receptor (GABAAR) α1 subunit expression in brain regions associated with the regulation of ethanol behaviors in P2X4R KO mice. These findings add to evidence that P2X4Rs contribute to ethanol intake and indicate that there is a complex interaction between P2X4Rs, ethanol, and other neurotransmitter receptor systems. PMID:24671605

  9. Contribution of P2X4 receptors to ethanol intake in male C57BL/6 mice.

    PubMed

    Wyatt, Letisha R; Finn, Deborah A; Khoja, Sheraz; Yardley, Megan M; Asatryan, Liana; Alkana, Ronald L; Davies, Daryl L

    2014-06-01

    P2X receptors (P2XRs) are a family of cation-permeable ligand-gated ion channels activated by synaptically released extracellular adenosine 5'-triphosphate. The P2X4 subtype is abundantly expressed in the central nervous system and is sensitive to low intoxicating ethanol concentrations. Genetic meta-analyses identified the p2rx4 gene as a candidate gene for innate alcohol intake and/or preference. The current study used mice lacking the p2rx4 gene (knockout, KO) and wildtype (WT) C57BL/6 controls to test the hypothesis that P2X4Rs contribute to ethanol intake. The early acquisition and early maintenance phases of ethanol intake were measured with three different drinking procedures. Further, we tested the effects of ivermectin (IVM), a drug previously shown to reduce ethanol's effects on P2X4Rs and to reduce ethanol intake and preference, for its ability to differentially alter stable ethanol intake in KO and WT mice. Depending on the procedure and the concentration of the ethanol solution, ethanol intake was transiently increased in P2X4R KO versus WT mice during the acquisition of 24-h and limited access ethanol intake. IVM significantly reduced ethanol intake in P2X4R KO and WT mice, but the degree of reduction was 50 % less in the P2X4R KO mice. Western blot analysis identified significant changes in γ-aminobutyric acidA receptor α1 subunit expression in brain regions associated with the regulation of ethanol behaviors in P2X4R KO mice. These findings add to evidence that P2X4Rs contribute to ethanol intake and indicate that there is a complex interaction between P2X4Rs, ethanol, and other neurotransmitter receptor systems.

  10. microRNA targeting of the P2X7 purinoceptor opposes a contralateral epileptogenic focus in the hippocampus

    PubMed Central

    Jimenez-Mateos, Eva M.; Arribas-Blazquez, Marina; Sanz-Rodriguez, Amaya; Concannon, Caoimhin; Olivos-Ore, Luis A.; Reschke, Cristina R.; Mooney, Claire M.; Mooney, Catherine; Lugara, Eleonora; Morgan, James; Langa, Elena; Jimenez-Pacheco, Alba; Silva, Luiz Fernando Almeida; Mesuret, Guillaume; Boison, Detlev; Miras-Portugal, M. Teresa; Letavic, Michael; Artalejo, Antonio R.; Bhattacharya, Anindya; Diaz-Hernandez, Miguel; Henshall, David C.; Engel, Tobias

    2015-01-01

    The ATP-gated ionotropic P2X7 receptor (P2X7R) modulates glial activation, cytokine production and neurotransmitter release following brain injury. Levels of the P2X7R are increased in experimental and human epilepsy but the mechanisms controlling P2X7R expression remain poorly understood. Here we investigated P2X7R responses after focal-onset status epilepticus in mice, comparing changes in the damaged, ipsilateral hippocampus to the spared, contralateral hippocampus. P2X7R-gated inward currents were suppressed in the contralateral hippocampus and P2rx7 mRNA was selectively uploaded into the RNA-induced silencing complex (RISC), suggesting microRNA targeting. Analysis of RISC-loaded microRNAs using a high-throughput platform, as well as functional assays, suggested the P2X7R is a target of microRNA-22. Inhibition of microRNA-22 increased P2X7R expression and cytokine levels in the contralateral hippocampus after status epilepticus and resulted in more frequent spontaneous seizures in mice. The major pro-inflammatory and hyperexcitability effects of microRNA-22 silencing were prevented in P2rx7−/− mice or by treatment with a specific P2X7R antagonist. Finally, in vivo injection of microRNA-22 mimics transiently suppressed spontaneous seizures in mice. The present study supports a role for post-transcriptional regulation of the P2X7R and suggests therapeutic targeting of microRNA-22 may prevent inflammation and development of a secondary epileptogenic focus in the brain. PMID:26631939

  11. R270C polymorphism leads to loss of function of the canine P2X7 receptor.

    PubMed

    Spildrejorde, Mari; Bartlett, Rachael; Stokes, Leanne; Jalilian, Iman; Peranec, Michelle; Sluyter, Vanessa; Curtis, Belinda L; Skarratt, Kristen K; Skora, Amanda; Bakhsh, Tahani; Seavers, Aine; McArthur, Jason D; Dowton, Mark; Sluyter, Ronald

    2014-07-15

    The relative function of the P2X7 receptor, an ATP-gated ion channel, varies between humans due to polymorphisms in the P2RX7 gene. This study aimed to assess the functional impact of P2X7 variation in a random sample of the canine population. Blood and genomic DNA were obtained from 69 dogs selected as representatives of a cross section of different breeds. P2X7 function was determined by flow cytometric measurements of dye uptake and patch-clamp measurements of inward currents. P2X7 expression was determined by immunoblotting and immunocytochemistry. Sequencing was used to identify P2RX7 gene polymorphisms. P2X7 was cloned from an English springer spaniel, and point mutations were introduced into this receptor by site-directed mutagenesis. The relative function of P2X7 on monocytes varied between individual dogs. The canine P2RX7 gene encoded four missense polymorphisms: F103L and P452S, found in heterozygous and homozygous dosage, and R270C and R365Q, found only in heterozygous dosage. Moreover, R270C and R365Q were associated with the cocker spaniel and Labrador retriever, respectively. F103L, R270C, and R365Q but not P452S corresponded to decreased P2X7 function in monocytes but did not explain the majority of differences in P2X7 function between dogs, indicating that other factors contribute to this variability. Heterologous expression of site-directed mutants of P2X7 in human embryonic kidney-293 cells indicated that the R270C mutant was nonfunctional, the F103L and R365Q mutants had partly reduced function, and the P452S mutant functioned normally. Taken together, these data highlight that a R270C polymorphism has major functional impact on canine P2X7.

  12. Role of P2X7 Receptor in an Animal Model of Mania Induced by D-Amphetamine.

    PubMed

    Gubert, Carolina; Fries, Gabriel Rodrigo; Pfaffenseller, Bianca; Ferrari, Pâmela; Coutinho-Silva, Robson; Morrone, Fernanda Bueno; Kapczinski, Flávio; Battastini, Ana Maria Oliveira

    2016-01-01

    The objective of this study was to explore the association between the P2X7 purinergic receptor (P2X7R) and neuroinflammation using a preclinical model of acute bipolar mania. We analyzed the modulatory effects of P2X7R agonist (3'-O-(4-benzoyl)benzoyl-adenosine 5'-triphosphate, BzATP) and antagonists (brilliant blue, BBG and 3-[[5-(2,3 dichlorophenyl)-1H-tetrazol-1-yl]methyl]pyridine hydrochloride, A438079) on assessments related to behavior (locomotor activity), neuroinflammation (interleukin-1 beta, IL-1β; tumor necrosis factor alpha, TNF-α; and interleukin- 6, IL-6), oxidative stress (thiobarbituric acid reactive substances, TBARS) and neuroplasticity (brain-derived neurotrophic factor, BDNF) markers in a pharmacological model of mania induced by acute and chronic treatment with D-amphetamine (AMPH) (2 mg/kg) in mice. An apparent lack of responsiveness to AMPH was observed in terms of the locomotor activity in animals with blocked P2X7R or with genetic deletion of P2X7R in knockout (P2X7R(-/-)) mice. Likewise, P2X7R participated in the AMPH-induced increase of the proinflammatory and excitotoxic environment, as demonstrated by the reversal of IL-1β, TNF-α, and TBARS levels caused by P2X7R blocking. Our results support the hypothesis that P2X7R plays a role in the neuroinflammation induced by AMPH in a preclinical model of mania, which could explain the altered behavior. The present data suggest that P2X7R may be a therapeutic target related to the neuroinflammation reported in bipolar disorder.

  13. Enhanced photocatalytic and photoelectrochemical activities of reduced TiO2-x/BiOCl heterojunctions

    NASA Astrophysics Data System (ADS)

    Fu, Rongrong; Zeng, Xiaoqiao; Ma, Lu; Gao, Shanmin; Wang, Qingyao; Wang, Zeyan; Huang, Baibiao; Dai, Ying; Lu, Jun

    2016-04-01

    A key issue to design highly efficient photoelectrodes for hydrogen production is how to prohibit the rapid carrier recombination. In order to use the visible light and reduce the recombination of electrons and holes, reduced TiO2-x/BiOCl heterojunctions are successfully synthesized and the photoelectrodes are assembled in this work. The effects of various Bi/Ti molar ratios on the structural, morphological, optical, photoelectrochemical and photocatalytic activities of the resultant samples are investigated systematically. The TiO2-x nanoparticles contain Ti3+, Ti2+, and oxygen vacancies (Ov), while the BiOCl nanosheets exposed {001} facet. Ultraviolet-visible diffuse reflectance spectroscopy (UV-vis DRS) results indicate that the existence of Ti3+, Ti2+ and Ov expand the light-response range. Linear scan voltammetry and electrochemical impedance spectroscopy results indicate that more efficient electron transportation is presented in the heterojunctions with the appropriate Bi/Ti molar ratio. Consequently, the reduced TiO2-x/BiOCl heterojunction with the most appropriate Bi/Ti molar ratio exhibits a high photocurrent density of 0.755 mA cm-2 with photoconversion efficiency up to 0.634%, 10.5 and 22.6 times larger than that of pure TiO2 and BiOCl. Furthermore, this heterojunction exhibit 48.38 and 12.54 times enhancement for the visible-light decomposition of rhodamine B compared with pure TiO2 and BiOCl.

  14. Development of the Functional Flow Block Diagram for the J-2X Rocket Engine System

    NASA Technical Reports Server (NTRS)

    White, Thomas; Stoller, Sandra L.; Greene, WIlliam D.; Christenson, Rick L.; Bowen, Barry C.

    2007-01-01

    The J-2X program calls for the upgrade of the Apollo-era Rocketdyne J-2 engine to higher power levels, using new materials and manufacturing techniques, and with more restrictive safety and reliability requirements than prior human-rated engines in NASA history. Such requirements demand a comprehensive systems engineering effort to ensure success. Pratt & Whitney Rocketdyne system engineers performed a functional analysis of the engine to establish the functional architecture. J-2X functions were captured in six major operational blocks. Each block was divided into sub-blocks or states. In each sub-block, functions necessary to perform each state were determined. A functional engine schematic consistent with the fidelity of the system model was defined for this analysis. The blocks, sub-blocks, and functions were sequentially numbered to differentiate the states in which the function were performed and to indicate the sequence of events. The Engine System was functionally partitioned, to provide separate and unique functional operators. Establishing unique functional operators as work output of the System Architecture process is novel in Liquid Propulsion Engine design. Each functional operator was described such that its unique functionality was identified. The decomposed functions were then allocated to the functional operators both of which were the inputs to the subsystem or component performance specifications. PWR also used a novel approach to identify and map the engine functional requirements to customer-specified functions. The final result was a comprehensive Functional Flow Block Diagram (FFBD) for the J-2X Engine System, decomposed to the component level and mapped to all functional requirements. This FFBD greatly facilitates component specification development, providing a well-defined trade space for functional trades at the subsystem and component level. It also provides a framework for function-based failure modes and effects analysis (FMEA), and a

  15. Pnicogen bonded complexes of PO2X (X = F, Cl) with nitrogen bases.

    PubMed

    Alkorta, Ibon; Elguero, José; Del Bene, Janet E

    2013-10-10

    An ab initio MP2/aug'-cc-pVTZ study has been carried out on complexes formed between PO2X (X = F and Cl) as the Lewis acids and a series of nitrogen bases ZN, including NH3, H2C═NH, NH2F, NP, NCH, NCF, NF3, and N2. Binding energies of these complexes vary from -10 to -150 kJ/mol, and P-N distances from 1.88 to 2.72 Å. Complexes ZN:PO2F have stronger P(...)N bonds and shorter P-N distances than the corresponding complexes ZN:PO2Cl. Charge transfer from the N lone pair through the π-hole to the P-X and P-O σ* orbitals leads to stabilization of these complexes, although charge-transfer energies can be evaluated only for complexes with binding energies less than -71 kJ/mol. Complexation of PO2X with the strongest bases leads to P···N bonds with a significant degree of covalency, and P-N distances that approach the P-N distances in the molecules PO2NC and PO2NH2. In these complexes, the PO2X molecules distort from planarity. Changes in (31)P absolute chemical shieldings upon complexation do not correlate with changes in charges on P, although they do correlate with the binding energies of the complexes. EOM-CCSD spin-spin coupling constants (1p)J(P-N) are dominated by the Fermi-contact term, which is an excellent approximation to total J. (1p)J(P-N) values are small at long distances, increase as the distance decreases, but then decrease at short P-N distances. At the shortest distances, values of (1p)J(P-N) approach (1)J(P-N) for the molecules PO2NC and PO2NH2.

  16. Sn cation valency dependence in cation exchange reactions involving Cu(2-x)Se nanocrystals.

    PubMed

    De Trizio, Luca; Li, Hongbo; Casu, Alberto; Genovese, Alessandro; Sathya, Ayyappan; Messina, Gabriele C; Manna, Liberato

    2014-11-19

    We studied cation exchange reactions in colloidal Cu(2-x)Se nanocrystals (NCs) involving the replacement of Cu(+) cations with either Sn(2+) or Sn(4+) cations. This is a model system in several aspects: first, the +2 and +4 oxidation states for tin are relatively stable; in addition, the phase of the Cu(2-x)Se NCs remains cubic regardless of the degree of copper deficiency (that is, "x") in the NC lattice. Also, Sn(4+) ions are comparable in size to the Cu(+) ions, while Sn(2+) ones are much larger. We show here that the valency of the entering Sn ions dictates the structure and composition not only of the final products but also of the intermediate steps of the exchange. When Sn(4+) cations are used, alloyed Cu(2-4y)Sn(y)Se NCs (with y ≤ 0.33) are formed as intermediates, with almost no distortion of the anion framework, apart from a small contraction. In this exchange reaction the final stoichiometry of the NCs cannot go beyond Cu0.66Sn0.33Se (that is Cu2SnSe3), as any further replacement of Cu(+) cations with Sn(4+) cations would require a drastic reorganization of the anion framework, which is not possible at the reaction conditions of the experiments. When instead Sn(2+) cations are employed, SnSe NCs are formed, mostly in the orthorhombic phase, with significant, albeit not drastic, distortion of the anion framework. Intermediate steps in this exchange reaction are represented by Janus-type Cu(2-x)Se/SnSe heterostructures, with no Cu-Sn-Se alloys.

  17. Sn Cation Valency Dependence in Cation Exchange Reactions Involving Cu2-xSe Nanocrystals

    PubMed Central

    2014-01-01

    We studied cation exchange reactions in colloidal Cu2-xSe nanocrystals (NCs) involving the replacement of Cu+ cations with either Sn2+ or Sn4+ cations. This is a model system in several aspects: first, the +2 and +4 oxidation states for tin are relatively stable; in addition, the phase of the Cu2-xSe NCs remains cubic regardless of the degree of copper deficiency (that is, “x”) in the NC lattice. Also, Sn4+ ions are comparable in size to the Cu+ ions, while Sn2+ ones are much larger. We show here that the valency of the entering Sn ions dictates the structure and composition not only of the final products but also of the intermediate steps of the exchange. When Sn4+ cations are used, alloyed Cu2–4ySnySe NCs (with y ≤ 0.33) are formed as intermediates, with almost no distortion of the anion framework, apart from a small contraction. In this exchange reaction the final stoichiometry of the NCs cannot go beyond Cu0.66Sn0.33Se (that is Cu2SnSe3), as any further replacement of Cu+ cations with Sn4+ cations would require a drastic reorganization of the anion framework, which is not possible at the reaction conditions of the experiments. When instead Sn2+ cations are employed, SnSe NCs are formed, mostly in the orthorhombic phase, with significant, albeit not drastic, distortion of the anion framework. Intermediate steps in this exchange reaction are represented by Janus-type Cu2-xSe/SnSe heterostructures, with no Cu–Sn–Se alloys. PMID:25340627

  18. Modulation of P2X4/P2X7/Pannexin-1 sensitivity to extracellular ATP via Ivermectin induces a non-apoptotic and inflammatory form of cancer cell death

    PubMed Central

    Draganov, Dobrin; Gopalakrishna-Pillai, Sailesh; Chen, Yun-Ru; Zuckerman, Neta; Moeller, Sara; Wang, Carrie; Ann, David; Lee, Peter P.

    2015-01-01

    Overexpression of P2X7 receptors correlates with tumor growth and metastasis. Yet, release of ATP is associated with immunogenic cancer cell death as well as inflammatory responses caused by necrotic cell death at sites of trauma or ischemia-reperfusion injury. Using an FDA-approved anti-parasitic agent Ivermectin as a prototype agent to allosterically modulate P2X4 receptors, we can switch the balance between the dual pro-survival and cytotoxic functions of purinergic signaling in breast cancer cells. This is mediated through augmented opening of the P2X4/P2X7-gated Pannexin-1 channels that drives a mixed apoptotic and necrotic mode of cell death associated with activation of caspase-1 and is consistent with pyroptosis. We show that cancer cell death is dependent on ATP release and death signals downstream of P2X7 receptors that can be reversed by inhibition of NADPH oxidases-generated ROS, Ca2+/Calmodulin-dependent protein kinase II (CaMKII) or mitochondrial permeability transition pore (MPTP). Ivermectin induces autophagy and release of ATP and HMGB1, key mediators of inflammation. Potentiated P2X4/P2X7 signaling can be further linked to the ATP rich tumor microenvironment providing a mechanistic explanation for the tumor selectivity of purinergic receptors modulation and its potential to be used as a platform for integrated cancer immunotherapy. PMID:26552848

  19. Correlations between magnetism, electrical conductivity and structural ordering in rare earth hydrides REH 2+x

    NASA Astrophysics Data System (ADS)

    Burger, J. P.; Daou, J. N.; Vajda, P.

    1990-12-01

    The excess hydrogen concentration x has fundamental effects on the magnetic properties which are due to modification of the conduction electron density and the shape of the Fermi surface, to crystal field effects and to order-disorder transitions within the H sublattice. We discuss: i) the occurrence of commensurate (for x = 0) and non-commensurate (for x > 0) antiferromagnetic ordering; ii) the effects of the crystal field which give rise to a non-Kondo resistivity minimum for PrH 2; iii) the incoherent and coherent Kondo effects of CeH 2+x and its relation with magnetism and structural ordering.

  20. 2 x 2 TeV mu(superscript +) mu (superscript) collider

    SciTech Connect

    Mokhov, N.V.; Noble, R.J.

    1996-10-01

    The scenarios for high-luminosity 2 x 2 TeV and 250 x 250 GeV {mu}{sup +}{mu}{sup -} colliders are presented. Having a high physics potential, such a machine has specific physics and technical advantages and disadvantages when compared with an e{sup +}e{sup -} collider. Parameters for the candidate designs and the basic components - proton source, pion production and decay channel, cooling, acceleration and collider storage ring - are considered. Attention is paid to the areas mostly affecting the collider performance: targetry, energy spread, superconducting magnet survival, detector backgrounds, polarization, environmental issues. 13 refs., 9 figs., 4 tabs.

  1. Radiative corrections in SU/sub 2/ x U/sub 1/ LEP/SLC

    SciTech Connect

    Lynn, B.W.; Peskin, M.E.; Stuart, R.G.

    1985-06-01

    We show the sensitivity of various experimental measurements to one-loop radiative corrections in SU/sub 2/ x U/sub 1/. Models considered are the standard GSW model as well as extensions of it which include extra quarks and leptons, SUSY and certain technicolor models. The observation of longitudinal polarization is a great help in seeing these effects in asymmetries in e/sup +/e/sup -/ ..-->.. ..mu../sup +/..mu../sup -/, tau/sup +/tau/sup -/ on Z/sup 0/ resonance. 25 refs., 22 figs., 10 tabs.

  2. New coplanar waveguide feed network for 2 x 2 linearly tapered slot antenna subarray

    NASA Technical Reports Server (NTRS)

    Simons, Rainee N.; Perl, Thomas D.; Lee, Richard Q.

    1992-01-01

    A novel feed method is presently demonstrated for a 2 x 2 linearly tapered slot antenna (LTSA) on the basis of a coplanar-waveguide (CPW)-to-slotline transition and a coax-to-CPW in-phase, four-way power divider. The LTSA subarray exhibits excellent radiation patterns and return-loss characteristics at 18 GHz, and has symmetric beamwidth; its compactness renders it applicable as either a feed for a reflector antenna or as a building-block for large arrays.

  3. Electronic Origins of Large Thermoelectric Power Factor of LaOBiS2-xSex

    NASA Astrophysics Data System (ADS)

    Nishida, Atsuhiro; Nishiate, Hirotaka; Lee, Chul-Ho; Miura, Osuke; Mizuguchi, Yoshikazu

    2016-07-01

    We have examined the electrical transport properties of densified LaOBiS2-xSex, which constitutes a new family of thermoelectric materials. The power factor increases with increasing concentration of Se, i.e., Se substitution leads to an enhanced electrical conductivity, without suppression of the Seebeck coefficient. Hall measurements reveal that the carrier mobility increases with decreasing carrier concentration as Se doping, which is responsible for the low electrical resistivity and large absolute values of the Seebeck coefficient in the system.

  4. Superconductivity in layered ZrP2-x Se x with PbFCl-type structure

    NASA Astrophysics Data System (ADS)

    Ishida, Shigeyuki; Fujihisa, Hiroshi; Hase, Izumi; Yanagi, Yousuke; Kawashima, Kenji; Oka, Kunihiko; Gotoh, Yoshito; Yoshida, Yoshiyuki; Iyo, Akira; Eisaki, Hiroshi; Kito, Hijiri

    2016-05-01

    We performed a systematic study of the crystal structure, physical properties, and electronic structure of PbFCl-type ZrP2-x Se x (0.3 ≤ x ≤ 0.9). We successfully synthesized single-phase polycrystalline samples for the Se substitution range of 0.4 ≤ x ≤ 0.8. The crystal structure of the compound is characterized by the alternate stacking of a two-dimensional P square net and a Zr-(P1-x Se x ) network. ZrP2-x Se x exhibits a dome-like superconductivity phase diagram and has a maximum superconducting transition temperature (T c) of 6.3 K for x ≈ 0.6. Resistivity and Hall measurements indicated that electron-phonon scattering plays a dominant role and that electron-type carriers dominate charge transport. Specific heat measurements confirmed that ZrP2-x Se x exhibits bulk superconductivity. Further, the value of the specific heat jump at T c (ΔC/γT c ≈ 1.35) is in keeping with the BCS weak-coupling model. These facts suggest a rather conventional pairing mechanism in ZrP2-x Se x . The x dependence of T c can be explained on the basis of the density of states (DOS) for x ≤ 0.7, whereas the decrease in T c with an increase in the DOS for x = 0.8 needs further investigation. One possible reason for the suppression of superconductivity is that the PbFCl-type structure becomes unstable for x ≥ 0.8. The results of electronic structure calculations agree reasonably well with those of the experimental observations, suggesting that the Zrd band plays a primary role in determining the physical properties. Further, the calculations predict a significant change in the Fermi-surface topology for x ≥ 0.8 this is a probable reason for the decrease in T c as well as the instability of the PbFCl-type structure.

  5. Supramolecular Co(II)-[2 x 2] grids: metamagnetic behavior in a single molecule.

    PubMed

    Waldmann, Oliver; Ruben, Mario; Ziener, Ulrich; Müller, Paul; Lehn, Jean M

    2006-08-07

    The magnetic anisotropy of the supramolecular [2 x 2] grid [Co(II)4L4]8+, with a bis(bipyridyl)-pyrimidine-based ligand L, was investigated by single-crystal magnetization measurements at low temperatures. The magnetization curves exhibit metamagnetic-like behavior and are explained by the weak-exchange limit of a minimal spin Hamiltonian including Heisenberg exchange, easy-axis ligand fields, and the Zeeman term. It is also shown that the magnetic coupling strength can be varied by the substituent R1 in the two-position on the central pyrimidine group of the ligand L.

  6. Generators for the elliptic curve y2 = x3-nx II

    NASA Astrophysics Data System (ADS)

    Fujita, Yasutsugu; Terai, Nobuhiro

    2011-09-01

    Let E be an elliptic curve defined by y2 = x3-nx with n a positive integer. In our previous work, we gave several infinite families of n for which certain two points of infinite order can be in a system of generators for the Mordell-Weil group E(Q). In this paper, we extend this result and give those examples of infinite families of n for which the generators for rank three part of E(Q) can be explicitly described.

  7. Disappearance of antiferromagnetic spin excitations in overdoped La2-xSrxCuO4.

    PubMed

    Wakimoto, S; Yamada, K; Tranquada, J M; Frost, C D; Birgeneau, R J; Zhang, H

    2007-06-15

    Magnetic excitations for energies up to approximately 100 meV are studied for overdoped La(2-x)Sr(x)CuO(4) with x=0.25 and 0.30, using time-of-flight neutron spectroscopy. Comparison of spectra integrated over the width of an antiferromagnetic Brillouin zone demonstrates that the magnetic scattering at intermediate energies, 20

  8. 26. A sepia photograph, 7 1/2" x 8 1/2" oh ...

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

    26. A sepia photograph, 7 1/2" x 8 1/2" oh semi-matte paper, aerial oblique of central Terre Haute with negative inscribed letters (prints on positive as white) along the bottom margin, "(02105-631K-118) (3-10-37. 10:30A) (R-1000) (State Normal College, Terre Haute, Ind.)" This view taken looking east shows the gas building in the near foreground right. On the reverse in red pencil, "Campus Scenes 10" and in black pencil, "1937". Source: Indiana State University Archives. - John T. Beasley Building, 632 Cherry Street (between Sixth & Seventh Streets), Terre Haute, Vigo County, IN

  9. Gaussian effective potential for the standard model SU(2)xU(1) electroweak theory

    SciTech Connect

    Siringo, Fabio; Marotta, Luca

    2008-07-01

    The Gaussian effective potential is derived for the non-Abelian SU(2)xU(1) gauge theory of electroweak interactions. At variance with naive derivations, the Gaussian effective potential is proven to be a genuine variational tool in any gauge. The role of ghosts is discussed and the unitarity gauge is shown to be the only choice which allows calculability without insertion of further approximations. The full non-Abelian calculation confirms the existence of a light Higgs boson in the nonperturbative strong coupling regime of the Higgs sector.

  10. Operating manual holographic interferometry system for 2 x 2 foot transonic wind tunnel

    NASA Technical Reports Server (NTRS)

    Craig, J. E.

    1981-01-01

    A holographic interferometer system was installed in a 2X2 foot transonic wind tunnel. The system incorporates a modern, 10 pps, Nd:YAG pulsed laser which provides reliable operation and is easy to align. The spatial filtering requirements of the unstable resonator beam are described as well as the integration of the system into the existing Schieren system. A two plate holographic interferometer is used to reconstruct flow field data. For static wind tunnel models the single exposure holograms are recorded in the usual manner; however, for dynamic models such as oscillating airfoils, synchronous laser hologram recording is used.

  11. Magnetic phase transitions in PrMn 2- xCr xGe 2

    NASA Astrophysics Data System (ADS)

    Dincer, I.; Elerman, Y.; Elmali, A.; Ehrenberg, H.; Fuess, H.; Duman, E.; Acet, M.

    2002-07-01

    The structural and magnetic properties of PrMn 2- xCr xGe 2 (0⩽ x⩽1.0) were studied by X-ray diffraction and magnetization measurements. The powder samples crystallize in the ThCr 2Si 2-type structure, and the lattice constants at room temperature show almost no variation as Cr substitutes Mn. The observed phase transitions are summarized in a proposed magnetic x- T phase diagram and compared with previous Moessbauer spectroscopy and neutron diffraction results for x=0.

  12. Detection device

    DOEpatents

    Smith, Jay E.

    1984-01-01

    The present invention is directed to a detection device comprising: (1) an entrance chamber, (2) a central chamber, and (3) an exit chamber. The central chamber includes an ionizing gas, anode, and means for connecting the anode with an external power supply and pulse counter.

  13. Detection device

    DOEpatents

    Smith, J.E.

    1981-02-27

    The present invention is directed to a detection device comprising: (1) an entrance chamber; (2) a central chamber; and (3) an exit chamber. The central chamber includes an ionizing gas, anode, and means for connecting the anode with an external power supply and pulse counter.

  14. Electrochemical device

    DOEpatents

    Grimes, Patrick G.; Einstein, Harry; Bellows, Richard J.

    1988-01-12

    A tunnel protected electrochemical device features channels fluidically communicating between manifold, tunnels and cells. The channels are designed to provide the most efficient use of auxiliary power. The channels have a greater hydraulic pressure drop and electrical resistance than the manifold. This will provide a design with the optimum auxiliary energy requirements.

  15. Cleaning devices

    NASA Technical Reports Server (NTRS)

    Schneider, Horst W. (Inventor)

    1981-01-01

    Cleaning devices are described which include a vacuum cleaner nozzle with a sharp rim for directing incoming air down against the floor; a vacuum cleaner wherein electrostatically charged brushes that brush dirt off a floor, are electrically grounded to remove charges that could tend to hold dirt to the brushes; a vacuum cleaner head having slots that form a pair of counter-rotating vortices, and that includes an outlet that blows a stream of air at the floor region which lies between the vortices; a cleaning device that sweeps a group of brushes against the ground along a first direction, and then sweeps them along the same ground area but in a second direction angled from the first by an amount such as 90.degree., to sweep up particles lying in crevices extending along any direction; a device that gently cleans a surface to remove bacteria for analysis, including an inclined wall along which cleaning fluid flows onto the surface, a vacuum chamber for drawing in the cleaning fluid, and a dividing wall spaced slightly from the surface to separate the fluid source from the vacuum cleaner chamber; and a device for providing pulses of pressured air including a chamber to which pressured air is supplied, a ball that circulates around the chamber to repeatedly close an outlet, and an air source that directs air circumferentially to move the ball around the chamber.

  16. [Intrauterine devices].

    PubMed

    Delavest, P; Engelmann, P

    1980-12-11

    Medicated IUDs such as copper IUDs and progesterone-releasing IUDs represent a new development in this form of contraception. All IUDs act by causing an inflammatory reaction at the endometrial level. Techniques of insertion vary from one model to the other; insertion always requires an experienced practitioner, and postabortion or midmenstruation insertions are to be preferred. Pregnancy with IUD in situ is a rare occurrence; the IUD must then be immediately removed. Ectopic pregnancies are about 5-10% of all pregnancies with the device in situ. IUD complications are uterine perforation, mostly done at time of insertion, and pelvic infection which, if untreated, can cause infertility; this is the reason why an IUD is never recommended to a nullipara. Pain and bleeding are the most common side effects. When the strings of the device are not visible, translocation of the device inside the uterine cavity must be suspected. The choice of the wrong type of IUD or a bad insertion can cause spontaneous expulsion of the device. IUD wearers must be regularly seen by a doctor; there is no correlation between IUD use and cervical or endometrial carcinoma.

  17. Ba(Zn1−2xMnxCux)2As2: A Bulk Form Diluted Ferromagnetic Semiconductor with Mn and Cu Codoping at Zn Sites

    PubMed Central

    Man, Huiyuan; Guo, Shengli; Sui, Yu; Guo, Yang; Chen, Bin; Wang, Hangdong; Ding, Cui; Ning, F.L.

    2015-01-01

    We report the synthesis and characterization of a bulk form diluted magnetic semiconductor Ba(Zn1−2xMnxCux)2As2 with the crystal structure identical to that of “122” family iron based superconductors and the antiferromagnet BaMn2As2. No ferromagnetic order occurs with (Zn, Mn) or (Zn, Cu) substitution in the parent compound BaZn2As2. Only when Zn is substituted by both Mn and Cu simultaneously, can the system undergo a ferromagnetic transition below TC ~ 70 K, followed by a magnetic glassy transition at Tf  ~ 35 K. AC susceptibility measurements for Ba(Zn0.75Mn0.125Cu0.125)2As2 reveal that Tf strongly depends on the applied frequency with and a DC magnetic field dependence of , demonstrating that a spin glass transition takes place at Tf. As large as −53% negative magnetoresistance has been observed in Ba(Zn1−2xMnxCux)2As2, enabling its possible application in memory devices. PMID:26492957

  18. Synthesis of rod and lath-shaped CuSe and tremella-shaped Cu2- x Se nanostructures at room temperature, and their optical properties

    NASA Astrophysics Data System (ADS)

    Hu, Pengfei; Cao, Yali

    2012-02-01

    The research for tunable synthesis and characterization techniques is important for the investigation of nanomaterials. Herein we developed old precipitation reaction for the morphology- and phase-tunable synthesis of copper selenides nanostructures at room temperature, avoiding tedious preparation of selenium precursors, such as selenite or selenosulfate. The molar ratio of Cu2+ and Se sources served the function of a switch for selectively synthesis of stoichiometric CuSe and non-stoichiometric Cu2- x Se. Nanorod and lath-like CuSe formed with excess of selenium source, while tremella-shaped Cu2- x Se responded to the 1:1 of Cu2+/Se or excess of copper source. The structures of nanocrystals, especially the lifelike surface, were characterized in detail by electron microscopy techniques, such as STEM. Novel nanostructures put up the excellent absorption properties in the visible light region, respectively, and could bear potential applications in solar cell devices in the future. This strategy offered a convenient, mild and energy-efficient route for the preparation of other mental chalcogenides nanocrystals with different morphologies or tunable phases.

  19. Efficient Catalysis of Hydrogen Evolution Reaction from WS2(1-x) P2x Nanoribbons.

    PubMed

    Shifa, Tofik Ahmed; Wang, Fengmei; Liu, Kaili; Cheng, Zhongzhou; Xu, Kai; Wang, Zhenxing; Zhan, Xueying; Jiang, Chao; He, Jun

    2017-02-06

    The rational design of Earth abundant electrocatalysts for efficiently catalyzing hydrogen evolution reaction (HER) is believed to lead to the generation of carbon neutral energy carrier. Owing to their fascinating chemical and physical properties, transition metal dichalcogenides (TMDs) are widely studied for this purpose. Of particular note is that doping by foreign atom can bring the advent of electronic perturbation, which affects the intrinsic catalytic property. Hence, through doping, the catalytic activity of such materials could be boosted. A rational synthesis approach that enables phosphorous atom to be doped into WS2 without inducing phase impurity to form WS2(1-x) P2x nanoribbon (NRs) is herein reported. It is found that the WS2(1-x) P2x NRs exhibit considerably enhanced HER performance, requiring only -98 mV versus reversible hydrogen electrode to achieve a current density of -10 mA cm(-2) . Such a high performance can be attributed to the ease of H-atom adsorption and desorption due to intrinsically tuned WS2 , and partial formation of NRs, a morphology wherein the exposure of active edges is more pronounced. This finding can provide a fertile ground for subsequent works aiming at tuning intrinsic catalytic activity of TMDs.

  20. Optical dispersion functions of Co2-xEuxVSn using ab-initio calculations

    NASA Astrophysics Data System (ADS)

    Mahmoud, Nada T.; Mousa, Ahmad A.; Juwhari, Hassan K.; Khalifeh, Jamil M.; Abu-Jafar, Mohammed S.

    2015-10-01

    The magnetic, electronic and optical properties of Co2-xEuxVSn alloys for selected concentrations (x = 0, 0.25, 0.50, 0.75 and 1.0) were investigated by means of density functional theory (DFT) calculations utilizing full potential linearized augmented plane wave (FP-LAPW) method. It was found that doping the Co2VSn alloy with rare-earth ions like Eu generates the nonstoichiometric Co2-xEuxVSn and changes its original behavior from half ferromagnetic material to a metallic one. In addition, the total magnetic moment was found to increase with increasing dopant concentration with maximum local magnetic contributions on the Eu-sites. The optical dielectric functions as well as their static value for all the above alloys were also investigated. Moreover, the absorption coefficient, reflectivity and refractive indices were calculated. All the optical calculations were found to agree well with the band structure calculations when determining the alloys’ half-metallic behavior. Finally, the nonstoichiometric metallic compounds found in this series might be useful in the flat panel industry as potential phosphors.

  1. Ge Quantum Dot Formation on Si (100)-2x1 with Surface Electronic Excitation

    NASA Astrophysics Data System (ADS)

    Oguzer, Ali

    2009-03-01

    The effect of laser-induced electronic excitations on the self-assembly of Ge quantum dots on Si (100)-2x1 grown by pulsed laser deposition is studied. The samples were first cleaned by using modified Shiraki method and then transferred into the deposition chamber. The vacuum system was then pumped down, baked for at least 12 hours, and the sample was then flashed to 1100 C in order for the 2x1 reconstruction to form. The experiment was conducted under a pressure ˜1x10-10 Torr. A Q-switched Nd:YAG laser (wavelength λ = 1064 nm, 10 Hz repetition rate) was used to ablate a Ge target. In-situ RHEED and STM and ex-situ AFM were used to study the morphology of the grown QD. The dependence of the QD morphology on substrate temperature and ablation and excitation laser energy density was studied. Electronic excitation is shown to affect the surface morphology. Laser irradiation of the Si substrate is shown to decrease the roughness of films grown at a substrate temperature of ˜450 ^oC. Electronic excitation also affected surface coverage ratio and cluster density and decreased the temperature required to form 3-dimensional quantum dots. Possible mechanisms involved will be discussed.

  2. Nanostructured Bi(2-x)Cu(x)S3 bulk materials with enhanced thermoelectric performance.

    PubMed

    Ge, Zhen-Hua; Zhang, Bo-Ping; Liu, Yong; Li, Jing-Feng

    2012-04-07

    Nanostructured Bi(2-x)Cu(x)S(3) (x = 0, 0.002, 0.005, 0.007, 0.01, 0.03) thermoelectric polycrystals were fabricated by combining mechanical alloying (MA) and spark plasma sintering (SPS) methods. The effect of Cu content on the microstructure and thermoelectric property of Bi(2-x)Cu(x)S(3) bulk samples was investigated. It was found that the subtle tailoring of Cu content could reduce both the electrical resistivity and the thermal conductivity at the same time, and consequently enhancing the thermoelectric property. A low electrical resistivity of 1.34 × 10(-4)Ω m(-1) and a low thermal conductivity of 0.52 W m(-1) K(-1) were obtained for the Bi(1.995)Cu(0.005)S(3) sample at 573 K. The low thermal conductivity is supposed to be due to the nanoscopic Cu-rich regions embedded in the host matrix. A peak ZT value of 0.34 at 573 K was achieved for the Bi(1.995)Cu(0.005)S(3) composition, which is the highest value in the Bi(2)S(3) system reported so far.

  3. Bromoenol lactone enhances the permeabilization of rat submandibular acinar cells by P2X7 agonists

    PubMed Central

    Chaïb, N; Kabré, E; Alzola, E; Pochet, S; Dehaye, J P

    2000-01-01

    The permeabilizing effect of P2X7 agonists was tested in rat submandibular acinar cells using the uptake of ethidium bromide as an index. The uptake of ethidium bromide by acini incubated at 37°C in the presence of 1 mM ATP increased with time and reached after 5 min about 10% of maximal uptake measured in the presence of digitonin. The response to ATP was dose-dependent (half-maximal concentration around 40 μM) and it was decreased when the temperature was lowered to 25°C. Benzoyl-ATP reproduced the response to ATP (half-maximal concentration around 10 μM). UTP or 2-methylthioATP had no effect. The permeabilization in response to ATP was blocked by oxidized ATP and by magnesium and inhibited by Coomassie blue. ATP increased the activity of a calcium-insensitive phospholipase A2 (iPLA2). Bromoenol lactone (BEL) inhibited the iPLA2 stimulated by ATP but potentiated the uptake of ethidium bromide in response to the purinergic agonist. From these results it is concluded that the activation of P2X7 receptors permeabilizes rat submandibular acinar cells. The pore-forming activity of the receptor might be negatively regulated by the concomitant activation of the iPLA2 by the receptor. PMID:10683195

  4. IPED2X: a robust pedigree reconstruction algorithm for complicated pedigrees.

    PubMed

    He, Dan; Eskin, Eleazar

    2014-12-01

    Reconstruction of family trees, or pedigree reconstruction, for a group of individuals is a fundamental problem in genetics. Some recent methods have been developed to reconstruct pedigrees using genotype data only. These methods are accurate and efficient for simple pedigrees which contain only siblings, where two individuals share the same pair of parents. A most recent method IPED2 is able to handle complicated pedigrees with half-sibling relationships, where two individuals share only one parent. However, the method is shown to miss many true positive half-sibling relationships as it removes all suspicious half-sibling relationships during the parent construction process. In this work, we propose a novel method IPED2X, which deploys a more robust algorithm for parent construction in the pedigrees by considering more possible operations rather than simple deletion. We convert the parent construction problem into a graph labeling problem and propose a more effective labeling algorithm. We show in our experiments that IPED2X is more powerful on capturing the true half-sibling relationships, which further leads to better reconstruction accuracy.

  5. SALT FOG TEST OF SAM2X5 COATED STAINLESS STEEL CYLINDER

    SciTech Connect

    Aprigliano, L F; Rebak, R B; Choi, J; Lian, T; Day, S D

    2007-04-23

    A salt fog test of an iron-based amorphous metal, SAM2X5, coated Type 316L stainless steel (SS316L) cylinder was made. The cylinder was 30-inch diameter by 88-inch long, and 3/8-inch thick. One end was welded shut with a SS316L end cap before coating. The body of the cylinder and the end cap were both coated. The cylinder was coated with SAM2X5 by the HVOF thermal spray process. The coating thickness was 0.015-inch to 0.019-inch thick. The cylinder was tested in a horizontal position. Also included in the test for reference purposes were five coupons (2-inch x 2-inch x 1/8-inch) of uncoated Type 1018 carbon steel (1018CS). The test used an abbreviated form of GM 9540P. Each cycle was 6 hours in duration and the cylinder and reference samples were exposed to a total of eight cycles. The cylinder was in relatively good condition after the test. Along the body of the cylinder only two pinpoint spot sized signs of rust were seen. The 1018CS reference specimens were extensively rusted.

  6. Electrical and optical properties of Cr2-xTixO3 thin films

    NASA Astrophysics Data System (ADS)

    Conde-Gallardo, A.; Cruz-Orea, A.; Zelaya-Angel, O.; Bartolo-Pèrez, P.

    2008-10-01

    Cr2-xTixO3 thin films with 0 <= x <= 1.82 were prepared on sapphire substrates by aerosol assisted chemical vapour deposition. The films in the 0 <= x <= 1.6 composition range grow preserving the α-chromite structure with a lattice constant that changes as a function of the titanium concentration [Ti]. However, films with x > 1.6 start to develop a crystalline phase that can be identified as Cr-doped TiO2. For the Cr2-xTixO3 films a Ti3+ → Cr3+ substitution is deduced from the crystalline structure and confirmed by XPS experiments. The increment in the lattice parameter agrees with the reduction in the optical band gap which goes from 3.50 eV to 2.70 eV for films with x = 0 and x ~ 1.6, respectively. At room temperature the electrical conductivity decreases as a function of the [Ti]. The thermal stimulated conductivity indicates a trap level at ~0.55 eV inside the gap in all the samples and the behaviour of the σ-T curves at higher temperatures indicates that the transport properties undergo a transition from a variable range hopping process to a more complicated process as the [Ti] increases.

  7. Anion disorder in lanthanoid zirconates Gd(2-x)Tb(x)Zr2O7.

    PubMed

    Reynolds, Emily; Blanchard, Peter E R; Kennedy, Brendan J; Ling, Chris D; Liu, Samuel; Avdeev, Max; Zhang, Zhaoming; Cuello, Gabriel J; Tadich, Anton; Jang, Ling-Yun

    2013-08-05

    The pyrochlore-defect fluorite order-disorder transition has been studied for a series of oxides of the type Gd(2-x)Tb(x)Zr2O7 by a combination of diffraction and spectroscopy techniques. Synchrotron X-ray diffraction data suggest an abrupt transition from the coexistence of pyrochlore and defect fluorite phases to a single defect fluorite phase with increasing Tb content. However neutron diffraction data, obtained at λ ≈ 0.497 Å for all Gd-containing samples to minimize absorption, not only provide evidence for independent ordering of the anion and cation sublattices but also suggest that the disorder transition across the pyrochlore-defect fluorite boundary of Ln2Zr2O7 is rather gradual. Such disorder was also evident in X-ray absorption measurements at the Zr L3-edge, which showed a gradual increase in the effective coordination number of the Zr from near 6-coordinate in the pyrochlore rich samples to near 7-coordinate in the Tb rich defect fluorites. These results indicate the presence of ordered domains throughout the defect fluorite region, and demonstrate the gradual nature of the order-disorder transition across the Gd(2-x)Tb(x)Zr2O7 series.

  8. Lipin-2 regulates NLRP3 inflammasome by affecting P2X7 receptor activation.

    PubMed

    Lordén, Gema; Sanjuán-García, Itziar; de Pablo, Nagore; Meana, Clara; Alvarez-Miguel, Inés; Pérez-García, M Teresa; Pelegrín, Pablo; Balsinde, Jesús; Balboa, María A

    2017-02-01

    Mutations in human LPIN2 produce a disease known as Majeed syndrome, the clinical manifestations of which are ameliorated by strategies that block IL-1β or its receptor. However the role of lipin-2 during IL-1β production remains elusive. We show here that lipin-2 controls excessive IL-1β formation in primary human and mouse macrophages by several mechanisms, including activation of the inflammasome NLRP3. Lipin-2 regulates MAPK activation, which mediates synthesis of pro-IL-1β during inflammasome priming. Lipin-2 also inhibits the activation and sensitization of the purinergic receptor P2X7 and K(+) efflux, apoptosis-associated speck-like protein with a CARD domain oligomerization, and caspase-1 processing, key events during inflammasome activation. Reduced levels of lipin-2 in macrophages lead to a decrease in cellular cholesterol levels. In fact, restoration of cholesterol concentrations in cells lacking lipin-2 decreases ion currents through the P2X7 receptor, and downstream events that drive IL-1β production. Furthermore, lipin-2-deficient mice exhibit increased sensitivity to high lipopolysaccharide doses. Collectively, our results unveil lipin-2 as a critical player in the negative regulation of NLRP3 inflammasome.

  9. Cycloadditions on diamond (100) 2 x 1: observation of lowered electron affinity due to hydrocarbon adsorption.

    PubMed

    Ouyang, Ti; Gao, Xingyu; Qi, Dongchen; Wee, Andrew Thye Shen; Loh, Kian Ping

    2006-03-23

    The adsorption of allyl alcohol, acrylic acid, and allyl chloride, as well as unsaturated organic molecules such as acetylene and 1,3 butadiene, on reconstructed diamond (100) 2 x 1 have been investigated using high-resolution electron energy loss (HREELS) spectroscopy and synchrotron radiation spectroscopy. The cycloadditions of these organic molecules produce chemically adsorbed adlayers with varying degree of coverages on the clean diamond. The organic adsorbed surface has a lowered electron affinity and shows a secondary electron yield that varies between 12 and 40% of the yield obtained from a fully hydrogenated diamond surface. The diamond surface can be functionalized with hydroxyl, carboxylic, and chlorine functionalities by the adsorption of these allyl organics. The [2 + 2] adduct of acetylene on the diamond (100) 2 x 1 surface can be observed. 1,3-butadiene attains a higher coverage as well as forms a thermally more stable adlayer on the diamond surface compared to the other organic molecules, due to its ability to undergo [4 + 2] cycloaddition.

  10. J-2X Gas Generator Development Testing at NASA Marshall Space Flight Center

    NASA Technical Reports Server (NTRS)

    Reynolds, D. C.; Hormonzian, Carlo

    2010-01-01

    NASA is developing a liquid oxygen/liquid hydrogen rocket engine for upper stage and trans-lunar applications of the Ares vehicles for the Constellation program. This engine, designated the J-2X, is a higher pressure, higher thrust variant of the Apollo-era J-2 engine. Development was contracted to Pratt & Whitney Rocketdyne in 2006. Over the past several years, two phases of testing have been completed on the development of the gas generator for the J-2X engine. The hardware has progressed through a variety of workhorse injector, chamber, and feed system configurations. Several of these configurations have resulted in combustion instability of the gas generator assembly. Development of the final configuration of workhorse hardware (which will ultimately be used to verify critical requirements on a component level) has required a balance between changes in the injector and chamber hardware in order to successfully mitigate the combustion instability without sacrificing other engine system requirements. This paper provides an overview of the two completed test series, performed at NASA s Marshall Space Flight Center. The requirements, facility setup, hardware configurations, and test series progression are detailed. Significant levels of analysis have been performed in order to provide design solutions to mitigate the combustion stability issues, and these are briefly covered. Also discussed are the results of analyses related to either anomalous readings or off-nominal testing throughout the two test series.

  11. P2X7 receptor-mediated calcium dynamics in HEK293 cells: experimental characterization and modelling approach

    NASA Astrophysics Data System (ADS)

    Di Garbo, A.; Alloisio, S.; Nobile, M.

    2012-04-01

    The P2X7 receptor (P2X7R) induces ionotropic Ca2 + signalling in different cell types. It plays an important role in the immune response and in the nervous system. Here, the mechanisms underlying intracellular Ca2 + variations evoked by 3‧-O-(4-benzoyl)benzoyl-ATP (BzATP), a potent agonist of the P2X7R, in transfected HEK293 cells, are investigated both experimentally and theoretically. We propose a minimal model of P2X7R that is capable of reproducing, qualitatively and quantitatively, the experimental data. This approach was also adopted for the P2X7R variant, which lacks the entire C-terminus tail (trP2X7R). Then we introduce a biophysical model describing the Ca2 + dynamics in HEK293. Our model gives an account of the ionotropic Ca2 + influx evoked by BzATP on the basis of the kinetics model of P2X7R. To explain the complex Ca2 + responses evoked by BzATP, the model predicted that an impairment in Ca2 + extrusion flux through the plasma membrane is a key factor for Ca2 + homeostasis in HEK293 cells.

  12. P2X7 receptor antagonism improves renal blood flow and oxygenation in angiotensin-II infused rats

    PubMed Central

    Menzies, Robert I.; Howarth, Amelia R.; Unwin, Robert J.; Tam, Frederick W.K.; Mullins, John J.; Bailey, Matthew A.

    2015-01-01

    Chronic activation of the renin angiotensin system promotes hypertension, renal microvascular dysfunction, tissue hypoxia and inflammation. We found previously that the injurious response to excess angiotensin II (ANGII) is greater in F344 rats, whereas Lewis rats are renoprotected, despite similar hypertension. We further identified p2rx7, encoding the P2X7 receptor (P2X7R), as a candidate gene for differential susceptibility and here we have tested the hypothesis that activation of P2X7R promotes vascular dysfunction under high ANGII tone. 14-day infusion of ANGII at 30ng/min into F344 rats increased blood pressure by ~15mmHg without inducing fibrosis or albuminuria. In vivo pressure natriuresis was suppressed, medullary perfusion reduced by ~50% and the cortico-medullary oxygenation gradient disrupted. Selective P2X7R antagonism restored pressure natriuresis, promoting a significant leftward shift in the intercept and increasing the slope. Sodium excretion was increased 6 fold and blood pressure normalized. The specific P2X7R antagonist AZ11657312 increased renal medullary perfusion, but only in ANGII-treated rats. Tissue oxygenation was improved by P2X7R blockade, particularly in poorly oxygenated regions of the kidney. Activation of P2X7R induces microvascular dysfunction and regional hypoxia when ANGII is elevated. These pro-inflammatory effects may contribute to progression of renal injury induced by chronic ANGII. PMID:26108066

  13. P2X7 Receptor Activation Impairs Exogenous MHC Class I Oligopeptides Presentation in Antigen Presenting Cells

    PubMed Central

    Baroja-Mazo, Alberto; Barberà-Cremades, Maria; Pelegrín, Pablo

    2013-01-01

    Major histocompatibility complex class I (MHC I) on antigen presenting cells (APCs) is a potent molecule to activate CD8+ T cells and initiate immunity. P2X7 receptors (P2X7Rs) are present on the plasma membrane of APCs to sense the extracellular danger signal adenosine-5′-triphosphate (ATP). P2X7R activates the inflammasome and the release of IL-1β in macrophages and other immune cells to initiate the inflammatory response. Here we show that P2X7R stimulation by ATP in APCs decreased the amount of MHC I at the plasma membrane. Specific antagonism or genetic ablation of P2X7R inhibited the effects of ATP on levels of cellular MHC I. Furthermore, P2X7R stimulation was able to inhibit activation of CD8+ T cells via specific MHC I-oligopeptide complexes. Our study suggests that P2X7R activation on APCs is a novel inhibitor of adaptive CD8+ T cell immunity. PMID:23940597

  14. Effect of P2X7 Receptor Knockout on AQP-5 Expression of Type I Alveolar Epithelial Cells

    PubMed Central

    Ebeling, Georg; Bläsche, Robert; Hofmann, Falk; Augstein, Antje; Kasper, Michael; Barth, Kathrin

    2014-01-01

    P2X7 receptors, ATP-gated cation channels, are specifically expressed in alveolar epithelial cells. The pathophysiological function of this lung cell type, except a recently reported putative involvement in surfactant secretion, is unknown. In addition, P2X7 receptor-deficient mice show reduced inflammation and lung fibrosis after exposure with bleomycin. To elucidate the role of the P2X7 receptor in alveolar epithelial type I cells we characterized the pulmonary phenotype of P2X7 receptor knockout mice by using immunohistochemistry, western blot analysis and real-time RT PCR. No pathomorphological signs of fibrosis were found. Results revealed, however, a remarkable loss of aquaporin-5 protein and mRNA in young knockout animals. Additional in vitro experiments with bleomycin treated precision cut lung slices showed a greater sensitivity of the P2X7 receptor knockout mice in terms of aquaporin-5 reduction as wild type animals. Finally, P2X7 receptor function was examined by using the alveolar epithelial cell lines E10 and MLE-12 for stimulation experiments with bleomycin. The in vitro activation of P2X7 receptor was connected with an increase of aquaporin-5, whereas the inhibition of the receptor with oxidized ATP resulted in down regulation of aquaporin-5. The early loss of aquaporin-5 which can be found in different pulmonary fibrosis models does not implicate a specific pathogenetic role during fibrogenesis. PMID:24941004

  15. P2X7 receptor-mediated killing of an intracellular parasite, Toxoplasma gondii, by human and murine macrophages1

    PubMed Central

    Lees, Michael P.; Fuller, Stephen J.; McLeod, Rima; Boulter, Nicola R.; Miller, Catherine M.; Zakrzewski, Alana M.; Mui, Ernest J.; Witola, William H.; Coyne, Jessica J.; Hargrave, Aubrey C.; Jamieson, Sarra E.; Blackwell, Jenefer M.; Wiley, James S.; Smith, Nicholas C.

    2010-01-01

    The P2X7 receptor (P2X7R)4 is highly expressed on the macrophage cell surface and activation of infected cells by extracellular ATP has been shown to kill intracellular bacteria and parasites. Furthermore, single nucleotide polymorphisms (SNPs) that decrease receptor function reduce the ability of human macrophages to kill Mycobacterium tuberculosis and are associated with extrapulmonary tuberculosis. In this paper we show that macrophages from people with the 1513C (rs3751143) loss-of-function P2X7R SNP are less effective in killing intracellular Toxoplasma gondii after exposure to ATP compared with macrophages from people with the 1513A wild-type allele. Supporting a P2X7R-specific effect on T. gondii, macrophages from P2X7R knock-out mice (P2X7R−/−) are unable to kill T. gondii as effectively as macrophages from wild-type mice. We show that P2X7R-mediated T. gondii killing occurs in parallel with host cell apoptosis and is independent of NO production. PMID:20488797

  16. Intersubunit Physical Couplings Fostered By The Left Flipper Domain Facilitate Channel Opening Of P2X4 Receptors.

    PubMed

    Wang, Jin; Sun, Liang-Fei; Cui, Wen-Wen; Zhao, Wen-Shan; Ma, Xue-Fei; Li, Bin; Liu, Yan; Yang, Yang; Hu, You-Min; Huang, Li-Dong; Cheng, Xiao-Yang; Li, Lingyong; Lu, Xiang-Yang; Tian, Yun; Yu, Ye

    2017-03-16

    P2X receptors are ATP-gated trimeric channels with important roles in diverse pathophysiological functions. A detailed understanding of the mechanism underlying the gating process of these receptors is thus fundamentally important and may open new therapeutic avenues. The left flipper (LF) domain of P2X receptors is a flexible loop structure and its coordinated motions together with the dorsal fin (DF) domain are crucial for the channel gating of the P2X receptors. However, the mechanism underlying the crucial role of the LF domain in the channel gating remains obscure. Here, we propose that the ATP-induced allosteric changes of the LF domain enable it to foster intersubunit physical couplings among the DF and two lower body domains, which is pivotal for the channel gating of P2X4 receptors. Metadynamics analysis indicated that these newly established intersubunit couplings correlate well with the ATP-bound open state of the receptors. Moreover, weakening or strengthening these physical interactions with engineered intersubunit metal bridges remarkably decreased or increased the open probability of the receptors, respectively. Further disulfide crosslinking and covalent modification confirmed that the intersubunit physical couplings among the DF and two lower body domains fostered by the LF domain at the open state act as an integrated structural element that is stringently required for the channel gating of P2X4 receptors. Our observations provide new mechanistic insights into P2X receptor activation and will stimulate development of new allosteric modulators of P2X receptors.

  17. TRPM7 is a molecular substrate of ATP-evoked P2X7-like currents in tumor cells

    PubMed Central

    Nörenberg, Wolfgang; Plötz, Tanja; Sobottka, Helga; Chubanov, Vladimir; Mittermeier, Lorenz; Kalwa, Hermann; Aigner, Achim

    2016-01-01

    Within the ion channel–coupled purine receptor (P2X) family, P2X7 has gained particular interest because of its role in immune responses and in the growth control of several malignancies. Typical hallmarks of P2X7 are nonselective and noninactivating cation currents that are elicited by high concentrations (0.1–10 mM) of extracellular ATP. Here, we observe spurious ATP-induced currents in HEK293 cells that neither express P2X7 nor display ATP-induced Ca2+ influx or Yo-Pro-1 uptake. Although the biophysical properties of these ionic currents resemble those of P2X7 in terms of their reversal potential close to 0 mV, nonrectifying current-voltage relationship, current run-up during repeated ATP application, and augmentation in bath solutions containing low divalent cation (DIC) concentrations, they are poorly inhibited by established P2X7 antagonists. Because high ATP concentrations reduce the availability of DICs, these findings prompted us to ask whether other channel entities may become activated by our experimental regimen. Indeed, a bath solution with no added DICs yields similar currents and also a rapidly inactivating Na+-selective conductance. We provide evidence that TRPM7 and ASIC1a (acid-sensing ion channel type Ia)-like channels account for these noninactivating and phasic current components, respectively. Furthermore, we find ATP-induced currents in rat C6 glioma cells, which lack functional P2X receptors but express TRPM7. Thus, the observation of an atypical P2X7-like conductance may be caused by the activation of TRPM7 by ATP, which scavenges free DICs and thereby releases TRPM7 from permeation block. Because TRPM7 has a critical role in controlling the intracellular Mg2+ homeostasis and regulating tumor growth, these data imply that the proposed role of P2X7 in C6 glioma cell proliferation deserves reevaluation. PMID:27185858

  18. The preparation of nitrogen-doped TiO 2- xN x photocatalyst coated on hollow glass microbeads

    NASA Astrophysics Data System (ADS)

    Shifu, Chen; Xuqiang, Liu; Yunzhang, Liu; Gengyu, Cao

    2007-01-01

    In this paper, the effective method for nitrogen-doped TiO 2- xN x photocatalyst coated on hollow glass microbeads is described, which uses titanium tetraisopropoxide [Ti( iso-OC 3H 7) 4] as the raw materials and gaseous ammonia as a heat treatment atmosphere. The effects of heat treatment temperature and time on the photocatalytic activity of TiO 2- xN x/beads are studied. The photocatalyst is characterized by the UV-vis diffuse reflection spectroscopy, X-ray photoelectron spectroscopy (XPS), X-ray powder diffraction (XRD), Brunauer-Emmett-Teller (BET) analysis and scanning electron microscopy (SEM). The results show that when the TiO 2- xN x/beads is heated at 650 °C for 5 h, the photocatalytic activity of the TiO 2- xN x/beads is the best. Compared with TiO 2, the photoabsorption wavelength range of nitrogen-doped TiO 2- xN x red shifts of about 60 nm, and the photoabsorption intensity increases as well. The photocatalytic activity of the TiO 2- xN x/beads is higher than that of the TiO 2/beads under visible light irradiation. The presence of nitrogen neither influences on the transformation of anatase to rutile, nor creates new crystal phases. When the TiO 2- xN x/beads is heated at 650 °C for 5 h, the amount of nitrogen-doped is 0.53 wt.% in the TiO 2- xN x. As the density of TiO 2- xN x/beads prepared is lower than 1.0 g/cm 3, it may float on water surface and use broader sunlight spectrum directly.

  19. Regulation of the P2X7R by microRNA-216b in human breast cancer

    SciTech Connect

    Zheng, Luming; Zhang, Xukui; Yang, Feng; Zhu, Jian; Zhou, Peng; Yu, Fang; Hou, Lei; Xiao, Lei; He, Qingqing; Wang, Baocheng

    2014-09-12

    Highlights: • We suggest the expression level of miR-216b and P2X7R in breast cancer tissues and cell lines. • We demonstrated that miR-216b directly targets and inhibits P2X7R. • We suggested miR-216b can attenuate ATP/P2X7R signaling pathways and induced Bcl-2/caspase-3 pathway. - Abstract: Breast cancer is the most common cancer in women around the world. However, the molecular mechanisms underlying breast cancer pathogenesis are only partially understood. Here, in this study, we found that P2X7R was up-regulated and miR-216b was down-regulated in breast cancer cell lines and tissues. Using bioinformatic analysis and 3′UTR luciferase reporter assay, we determined P2X7R can be directly targeted by miR-216b, which can down-regulate endogenous P2X7R mRNA and protein levels. Ectopic expression of miR-216b mimics leads to inhibited cell growth and apoptosis, while blocking expression of the miR-216b results in increased cell proliferation. Furthermore, our findings demonstrate that knockdown of P2X7R promotes apoptosis in breast cancer cells through down-regulating Bcl-2 and increasing the cleavage caspase-3 protein level. Finally, we confirmed that down-regulation of miR-216b in breast cancer is inversely associated with P2X7R expression level. Together, these findings establish miR-216b as a novel regulator of P2X7R and a potential therapeutic target for breast cancer.

  20. Cell uptake, intracellular distribution, fate and reactive oxygen species generation of polymer brush engineered CeO2-x NPs

    NASA Astrophysics Data System (ADS)

    Qiu, Yuan; Rojas, Elena; Murray, Richard A.; Irigoyen, Joseba; Gregurec, Danijela; Castro-Hartmann, Pablo; Fledderman, Jana; Estrela-Lopis, Irina; Donath, Edwin; Moya, Sergio E.

    2015-04-01

    Cerium Oxide nanoparticles (CeO2-x NPs) are modified with polymer brushes of negatively charged poly (3-sulfopropylmethacrylate) (PSPM) and positively charged poly (2-(methacryloyloxy)ethyl-trimethylammonium chloride) (PMETAC) by Atom Transfer Radical Polymerisation (ATRP). CeO2-x NPs are fluorescently labelled by covalently attaching Alexa Fluor® 488/Fluorescein isothiocyanate to the NP surface prior to polymerisation. Cell uptake, intracellular distribution and the impact on the generation of intracellular Reactive Oxygen Species (ROS) with respect to CeO2-x NPs are studied by means of Raman Confocal Microscopy (CRM), Transmission Electron Microscopy (TEM) and Inductively Coupled Plasma Mass Spectroscopy (ICP-MS). PSPM and PMETAC coated CeO2-x NPs show slower and less uptake compared to uncoated Brush modified NPs display a higher degree of co-localisation with cell endosomes and lysosomes after 24 h of incubation. They also show higher co-localisation with lipid bodies when compared to unmodified CeO2-x NPs. The brush coating does not prevent CeO2-x NPs from displaying antioxidant properties.Cerium Oxide nanoparticles (CeO2-x NPs) are modified with polymer brushes of negatively charged poly (3-sulfopropylmethacrylate) (PSPM) and positively charged poly (2-(methacryloyloxy)ethyl-trimethylammonium chloride) (PMETAC) by Atom Transfer Radical Polymerisation (ATRP). CeO2-x NPs are fluorescently labelled by covalently attaching Alexa Fluor® 488/Fluorescein isothiocyanate to the NP surface prior to polymerisation. Cell uptake, intracellular distribution and the impact on the generation of intracellular Reactive Oxygen Species (ROS) with respect to CeO2-x NPs are studied by means of Raman Confocal Microscopy (CRM), Transmission Electron Microscopy (TEM) and Inductively Coupled Plasma Mass Spectroscopy (ICP-MS). PSPM and PMETAC coated CeO2-x NPs show slower and less uptake compared to uncoated Brush modified NPs display a higher degree of co-localisation with cell

  1. P2X4 Receptor Reporter Mice: Sparse Brain Expression and Feeding-Related Presynaptic Facilitation in the Arcuate Nucleus

    PubMed Central

    Xu, Ji; Bernstein, Alexander M.; Wong, Angela; Lu, Xiao-Hong; Khoja, Sheraz; Yang, X. William; Davies, Daryl L.; Micevych, Paul; Sofroniew, Michael V.

    2016-01-01

    P2X4 receptors are ATP-gated cation channels that are widely expressed in the nervous system. To identify P2X4 receptor-expressing cells, we generated BAC transgenic mice expressing tdTomato under the control of the P2X4 receptor gene (P2rx4). We found sparse populations of tdTomato-positive neurons in most brain areas with patterns that matched P2X4 mRNA distribution. tdTomato expression within microglia was low but was increased by an experimental manipulation that triggered microglial activation. We found surprisingly high tdTomato expression in the hypothalamic arcuate nucleus (Arc) (i.e., within parts of the neural circuitry controlling feeding). Immunohistochemistry and genetic crosses of P2rx4 tdTomato mice with cell-specific GFP reporter lines showed that the tdTomato-expressing cells were mainly AgRP-NPY neurons and tanycytes. There was no electrophysiological evidence for functional expression of P2X4 receptors on AgRP-NPY neuron somata, but instead, we found clear evidence for functional presynaptic P2X4 receptor-mediated responses in terminals of AgRP-NPY neurons onto two of their postsynaptic targets (Arc POMC and paraventricular nucleus neurons), where ATP dramatically facilitated GABA release. The presynaptic responses onto POMC neurons, and the expression of tdTomato in AgRP-NPY neurons and tanycytes, were significantly decreased by food deprivation in male mice in a manner that was partially reversed by the satiety-related peptide leptin. Overall, we provide well-characterized tdTomato reporter mice to study P2X4-expressing cells in the brain, new insights on feeding-related regulation of presynaptic P2X4 receptor responses, and the rationale to explore extracellular ATP signaling in the control of feeding behaviors. SIGNIFICANCE STATEMENT Cells expressing ATP-gated P2X4 receptors have proven problematic to identify and study in brain slice preparations because P2X4 expression is sparse. To address this limitation, we generated and characterized

  2. Minority-spin t2g states and the degree of spin polarization in ferromagnetic metallic La2-2xSr1+2xMn2O7 (x = 0.38)

    NASA Astrophysics Data System (ADS)

    Sun, Z.; Wang, Q.; Douglas, J. F.; Lin, H.; Sahrakorpi, S.; Barbiellini, B.; Markiewicz, R. S.; Bansil, A.; Fedorov, A. V.; Rotenberg, E.; Zheng, H.; Mitchell, J. F.; Dessau, D. S.

    2013-11-01

    A half-metal is a material with conductive electrons of one spin orientation. This type of substance has been extensively searched for due to the fascinating physics as well as the potential applications for spintronics. Ferromagnetic manganites are considered to be good candidates, though there is no conclusive evidence for this notion. Here we show that the ferromagnet La2-2xSr1+2xMn2O7 (x = 0.38) possesses minority-spin states, challenging whether any of the manganites may be true half-metals. However, when electron transport properties are taken into account on the basis of the electronic band structure, we found that the La2-2xSr1+2xMn2O7 (x = 0.38) can essentially behave like a complete half metal.

  3. Minority-spin t(2g) states and the degree of spin polarization in ferromagnetic metallic La(2-2x)Sr(1+2x)Mn(2)O(7) (x = 0.38).

    PubMed

    Sun, Z; Wang, Q; Douglas, J F; Lin, H; Sahrakorpi, S; Barbiellini, B; Markiewicz, R S; Bansil, A; Fedorov, A V; Rotenberg, E; Zheng, H; Mitchell, J F; Dessau, D S

    2013-11-07

    A half-metal is a material with conductive electrons of one spin orientation. This type of substance has been extensively searched for due to the fascinating physics as well as the potential applications for spintronics. Ferromagnetic manganites are considered to be good candidates, though there is no conclusive evidence for this notion. Here we show that the ferromagnet La2-2xSr1+2xMn2O7 (x = 0.38) possesses minority-spin states, challenging whether any of the manganites may be true half-metals. However, when electron transport properties are taken into account on the basis of the electronic band structure, we found that the La2-2xSr1+2xMn2O7 (x = 0.38) can essentially behave like a complete half metal.

  4. Minority-spin t2g states and the degree of spin polarization in ferromagnetic metallic La2−2xSr1+2xMn2O7 (x = 0.38)

    PubMed Central

    Sun, Z.; Wang, Q.; Douglas, J. F.; Lin, H.; Sahrakorpi, S.; Barbiellini, B.; Markiewicz, R. S.; Bansil, A.; Fedorov, A. V.; Rotenberg, E.; Zheng, H.; Mitchell, J. F.; Dessau, D. S.

    2013-01-01

    A half-metal is a material with conductive electrons of one spin orientation. This type of substance has been extensively searched for due to the fascinating physics as well as the potential applications for spintronics. Ferromagnetic manganites are considered to be good candidates, though there is no conclusive evidence for this notion. Here we show that the ferromagnet La2−2xSr1+2xMn2O7 (x = 0.38) possesses minority-spin states, challenging whether any of the manganites may be true half-metals. However, when electron transport properties are taken into account on the basis of the electronic band structure, we found that the La2−2xSr1+2xMn2O7 (x = 0.38) can essentially behave like a complete half metal. PMID:24196704

  5. Single crystalline Pr{sub 2-x}Y{sub x}O{sub 3} (x=0-2) dielectrics on Si with tailored electronic and crystallographic structure

    SciTech Connect

    Seifarth, O.; Schubert, M. A.; Giussani, A.; Schroeder, T.; Klenov, D. O.; Schmeisser, D.

    2010-11-15

    Crystalline oxides on Si with tailored electronic and crystallographic properties are of importance for the integration of functional oxides or alternative semiconductors to enable novel device concepts in Si microelectronics. We present an electronic band gap study of single crystalline Pr{sub 2-x}Y{sub x}O{sub 3} (0{<=}x{<=}2) heterostructures on Si(111). The perfect solubility of the isomorphic bixbyites Pr{sub 2}O{sub 3} and Y{sub 2}O{sub 3} during molecular beam epitaxy thin film growth on Si enables a linear band gap tuning. Special focus is devoted to the determination of the electronic band offsets across the dielectric/Si interface. In addition, the composition x allows to control the crystallographic lattice parameter where, for example, Pr{sub 0.8}Y{sub 1.2}O{sub 3} enables the growth of fully lattice matched oxide heterostructures on Si.

  6. LOADING DEVICE

    DOEpatents

    Ohlinger, L.A.

    1958-10-01

    A device is presented for loading or charging bodies of fissionable material into a reactor. This device consists of a car, mounted on tracks, into which the fissionable materials may be placed at a remote area, transported to the reactor, and inserted without danger to the operating personnel. The car has mounted on it a heavily shielded magazine for holding a number of the radioactive bodies. The magazine is of a U-shaped configuration and is inclined to the horizontal plane, with a cap covering the elevated open end, and a remotely operated plunger at the lower, closed end. After the fissionable bodies are loaded in the magazine and transported to the reactor, the plunger inserts the body at the lower end of the magazine into the reactor, then is withdrawn, thereby allowing gravity to roll the remaining bodies into position for successive loading in a similar manner.

  7. Laser device

    DOEpatents

    Scott, Jill R.; Tremblay, Paul L.

    2008-08-19

    A laser device includes a virtual source configured to aim laser energy that originates from a true source. The virtual source has a vertical rotational axis during vertical motion of the virtual source and the vertical axis passes through an exit point from which the laser energy emanates independent of virtual source position. The emanating laser energy is collinear with an orientation line. The laser device includes a virtual source manipulation mechanism that positions the virtual source. The manipulation mechanism has a center of lateral pivot approximately coincident with a lateral index and a center of vertical pivot approximately coincident with a vertical index. The vertical index and lateral index intersect at an index origin. The virtual source and manipulation mechanism auto align the orientation line through the index origin during virtual source motion.

  8. Electrooptical Devices.

    DTIC Science & Technology

    1980-03-31

    Si N ’or Pl. The surface-related nature of the leakage currents was confirmed by testing the uncoated devices in several gaseous environments (O, NH ...later- tinre. Z-I.. Liau D. E. Mull .1. J. Ilsiebl J. N. Walpole T. A. Lind 711 G&InkA.P/ p I 643 6-C Fig. IV- t. Intensity distribution of an X-ray beam

  9. Closure device

    SciTech Connect

    Sable, D. E.

    1985-06-11

    A closure device connectible to a well head through which the polished rod of a rod string extends into a well tubing for operating pump means for moving well fluids to a surface flow conductor, the closure device having a tubular ram provided with a packing or plug for closing an annular passage between the polished rod and a tubular body connected to the well head above a lateral port of the tubular body, the tubular ram and the tubular body having thread means for moving the plug between an operative lower position wherein it closes the annular passage when the rod string is stationary and on inoperative upper position; seal means between the ram and the polished rod spaced above the plug; and a plurality of independent seal means between the ram and the tubular body operative when the plug is in its inoperative position. The plug of the closure device is especially adapted to operate under high temperature and pressure conditions of the well, as during steam injection operations when the rod string is stationary, to protect the seal means from high pressures and temperatures as well as any fluids which may be corrosive or otherwise deleterious to the substance of which the seal means are made.

  10. Characterization of thin films of the solid electrolyte Li(x)Mg(1-2x)Al(2+x)O4 (x = 0, 0.05, 0.15, 0.25).

    PubMed

    Put, Brecht; Vereecken, Philippe M; Mees, Maarten J; Rosciano, Fabio; Radu, Iuliana P; Stesmans, Andre

    2015-11-21

    RF-sputtered thin films of spinel Li(x)Mg(1-2x)Al(2+x)O4 were investigated for use as solid electrolyte. The usage of this material can enable the fabrication of a lattice matched battery stack, which is predicted to lead to superior battery performance. Spinel Li(x)Mg(1-2x)Al(2+x)O4 thin films, with stoichiometry (x) ranging between 0 and 0.25, were formed after a crystallization anneal as shown by X-ray diffraction and transmission electron microscopy. The stoichiometry of the films was evaluated by elastic recoil detection and Rutherford backscattering and found to be slightly aluminum rich. The excellent electronic insulation properties were confirmed by both current-voltage measurements as well as by copper plating tests. The electrochemical stability window of the material was probed using cyclic voltammetry. Lithium plating and stripping was observed together with the formation of a Li-Pt alloy, indicating that Li-ions passed through the film. This observation contradicted with impedance measurements at open circuit potential, which showed no apparent Li-ion conductivity of the film. Impedance spectroscopy as a function of potential showed the occurrence of Li-ion intercalation into the Li(x)Mg(1-2x)Al(2+x)O4 layers. When incorporating Li-ions in the material the ionic conductivity can be increased by 3 orders of magnitude. Therefore it is anticipated that the response of Li(x)Mg(1-2x)Al(2+x)O4 is more adequate for a buffer layer than as the solid electrolyte.

  11. Medical Device Safety

    MedlinePlus

    ... Home Medical Devices Medical Device Safety Medical Device Safety Share Tweet Linkedin Pin it More sharing options ... 17 More Medical Device Recalls Recent Medical Device Safety Communications FDA analyses and recommendations for patients and ...

  12. External incontinence devices

    MedlinePlus

    ... devices; Urinary incontinence - devices; Fecal incontinence - devices; Stool incontinence - devices ... of these different products are listed below. FECAL INCONTINENCE DEVICES There are many types of products for managing long-term diarrhea or fecal incontinence . ...

  13. The J-2X Upper Stage Engine: From Heritage to Hardware

    NASA Technical Reports Server (NTRS)

    Byrd, THomas

    2008-01-01

    NASA's Global Exploration Strategy requires safe, reliable, robust, efficient transportation to support sustainable operations from Earth to orbit and into the far reaches of the solar system. NASA selected the Ares I crew launch vehicle and the Ares V cargo launch vehicle to provide that transportation. Guiding principles in creating the architecture represented by the Ares vehicles were the maximum use of heritage hardware and legacy knowledge, particularly Space Shuttle assets, and commonality between the Ares vehicles where possible to streamline the hardware development approach and reduce programmatic, technical, and budget risks. The J-2X exemplifies those goals. It was selected by the Exploration Systems Architecture Study (ESAS) as the upper stage propulsion for the Ares I Upper Stage and the Ares V Earth Departure Stage (EDS). The J-2X is an evolved version ofthe historic J-2 engine that successfully powered the second stage of the Saturn I launch vehicle and the second and third stages of the Saturn V launch vehicle. The Constellation architecture, however, requires performance greater than its predecessor. The new architecture calls for larger payloads delivered to the Moon and demands greater loss of mission reliability and numerous other requirements associated with human rating that were not applied to the original J-2. As a result, the J-2X must operate at much higher temperatures, pressures, and flow rates than the heritage J-2, making it one of the highest performing gas generator cycle engines ever built, approaching the efficiency of more complex stage combustion engines. Development is focused on early risk mitigation, component and subassembly test, and engine system test. The development plans include testing engine components, including the subscale injector, main igniter, powerpack assembly (turbopumps, gas generator and associated ducting and structural mounts), full-scale gas generator, valves, and control software with hardware

  14. Streptococcus pneumoniae PBP2x mid-cell localization requires the C-terminal PASTA domains and is essential for cell shape maintenance.

    PubMed

    Peters, Katharina; Schweizer, Inga; Beilharz, Katrin; Stahlmann, Christoph; Veening, Jan-Willem; Hakenbeck, Regine; Denapaite, Dalia

    2014-05-01

    The transpeptidase activity of the essential penicillin-binding protein 2x (PBP2x) of Streptococcus pneumoniae is believed to be important for murein biosynthesis required for cell division. To study the molecular mechanism driving localization of PBP2x in live cells, we constructed a set of N-terminal GFP-PBP2x fusions under the control of a zinc-inducible promoter. The ectopic fusion protein localized at mid-cell. Cells showed no growth defects even in the absence of the genomic pbp2x, demonstrating that GFP-PBP2x is functional. Depletion of GFP-PBP2x resulted in severe morphological alterations, confirming the essentiality of PBP2x and demonstrating that PBP2x is required for cell division and not for cell elongation. A genetically or antibiotic inactivated GFP-PBP2x still localized at septal sites. Remarkably, the same was true for a GFP-PBP2x derivative containing a deletion of the central transpeptidase domain, although only in the absence of the protease/chaperone HtrA. Thus localization is independent of the catalytic transpeptidase domain but requires the C-terminal PASTA domains, identifying HtrA as targeting GFP-PBP2x derivatives. Finally, PBP2x was positioned at the septum similar to PBP1a and the PASTA domain containing StkP protein, confirming that PBP2x is a key element of the divisome complex.

  15. Postsynaptic P2X3-containing receptors in gustatory nerve fibres mediate responses to all taste qualities in mice

    PubMed Central

    Vandenbeuch, Aurelie; Larson, Eric D; Anderson, Catherine B; Smith, Steven A; Ford, Anthony P; Finger, Thomas E; Kinnamon, Sue C

    2015-01-01

    Abstract Taste buds release ATP to activate ionotropic purinoceptors composed of P2X2 and P2X3 subunits, present on the taste nerves. Mice with genetic deletion of P2X2 and P2X3 receptors (double knockout mice) lack responses to all taste stimuli presumably due to the absence of ATP-gated receptors on the afferent nerves. Recent experiments on the double knockout mice showed, however, that their taste buds fail to release ATP, suggesting the possibility of pleiotropic deficits in these global knockouts. To test further the role of postsynaptic P2X receptors in afferent signalling, we used AF-353, a selective antagonist of P2X3-containing receptors to inhibit the receptors acutely during taste nerve recording and behaviour. The specificity of AF-353 for P2X3-containing receptors was tested by recording Ca2+ transients to exogenously applied ATP in fura-2 loaded isolated geniculate ganglion neurons from wild-type and P2X3 knockout mice. ATP responses were completely inhibited by 10 μm or 100 μm AF-353, but neither concentration blocked responses in P2X3 single knockout mice wherein the ganglion cells express only P2X2-containing receptors. Furthermore, AF-353 had no effect on taste-evoked ATP release from taste buds. In wild-type mice, i.p. injection of AF-353 or simple application of the drug directly to the tongue, inhibited taste nerve responses to all taste qualities in a dose-dependent fashion. A brief access behavioural assay confirmed the electrophysiological results and showed that preference for a synthetic sweetener, SC-45647, was abolished following i.p. injection of AF-353. These data indicate that activation of P2X3-containing receptors is required for transmission of all taste qualities. Key points Acute inhibition of purinergic receptors with a selective P2X3 antagonist prevents transmission of information from taste buds to sensory nerves. The P2X3 antagonist has no effect on taste-evoked release of ATP, confirming the effect is postsynaptic. The

  16. Study of baicalin on sympathoexcitation induced by myocardial ischemia via P2X3 receptor in superior cervical ganglia.

    PubMed

    Zhang, Jun; Liu, Shuangmei; Xu, Baohua; Li, Guodong; Li, Guilin; Huang, An; Wu, Bing; Peng, Lichao; Song, Miaomiao; Xie, Qiuyu; Lin, Weijian; Xie, Wei; Wen, Shiyao; Zhang, Zhedong; Xu, Xiaoling; Liang, Shangdong

    2015-05-01

    After the myocardial ischemia, injured myocardial tissues released large quantity of ATP, which activated P2X3 receptor in superior cervical ganglia and made the SCG postganglionic neurons excited. Excitatory of sympathetic postganglionic efferent neurons increased the blood pressure and heart rates, which aggravated the myocardial ischemic injury. Baicalin has anti-inflammatory and anti-oxidant properties. Our study showed that baicalin reduced the incremental concentration of serum CK-MB, cTn-T, epinephrine and ATP, decreased the up-regulated expression levels of P2X3 mRNA and protein in SCG after MI, and then inhibited the sympathetic excitatory activity triggered by MI injury. These results indicated that baicalin acted on P2X3 receptor was involved in the transmission of sympathetic excitation after the myocardial ischemic injury. Baicalin might decrease sympathetic activity via inhibiting P2X3 receptor in rat SCG to protect the myocardium.

  17. P2X7 receptor-pannexin 1 hemichannel association: effect of extracellular calcium on membrane permeabilization.

    PubMed

    Poornima, V; Madhupriya, M; Kootar, S; Sujatha, G; Kumar, Arvind; Bera, Amal Kanti

    2012-03-01

    Activation of P2X(7) receptor (P2X(7)R) and pannexin have been implicated in membrane permeabilization associated with ischemic cell death and many other inflammatory processes. P2X(7)R has a unique property of forming large pore upon repeated or prolonged application of agonist like ATP or 2', 3'-(4-benzoyl) benzoyl ATP. It has been proposed that pannexin 1 (panx1) hemichannel associates with P2X(7)R to form large pore, though the actual mechanism is not yet understood. Calcium concentration in extracellular milieu drops in many patho-physiological conditions, e.g. ischemia, when P2X(7)R/pannexin is also known to be activated. Therefore, we hypothesize that extracellular calcium ([Ca(2+)](o)) plays an important role in the coupling of P2X(7)R-panx1 and subsequent membrane permeabilization. In this study we show that membrane permeability of the P2X(7)R and panx1 expressing N2A cell increases in ([Ca(2+)](o))-free solution. In [Ca(2+)](o)-free solution, fluorescent dye calcein trapped cells exhibited time-dependent dye leakage resulting in about 50% decrease of fluorescence intensity in 30 min. Control cells in 2 mM [Ca(2+)](o) did not show such leakage. Like N2A cells, mixed culture of neuron and glia, derived from hippocampal progenitor cells showed similar dye leakage. Dye leakage was blocked either by pannexin-specific blocker, carbenoxolone or P2X(7)R antagonists, Brilliant Blue G, and oxidized ATP. Furthermore P2X(7)R and panx1 were co-immunoprecipitated. The amount of P2X(7)R protein pulled-down with panx1, increased by twofold when cells were incubated 30 min in [Ca(2+)](o)-free buffer. Taken together, the results of this study demonstrate the activation and association of P2X(7)R-panx1, triggered by the removal of [Ca(2+)](o).

  18. Thermodynamic Properties of Heusler Fe2-x C ox M n S i

    NASA Astrophysics Data System (ADS)

    Ito, Masakazu; Furuta, Tatsuya; Kai, Keita; Taira, Atsushi; Onda, Keijiro; Shigeta, Iduru; Hiroi, Masahiko

    2017-04-01

    We investigated the thermodynamic properties of Heusler compounds Fe2-x C ox m n S i (0.00 ≤ x ≤ 2.00). The specific heats CP(T) for compounds with x ≤ 0.1 exhibit a λ-type anomaly arising from spin rearrangements at TR. With increasing x, TR decreases linearly and vanishes at x ∼ 0.169 . The magnetic entropy, STR, derived from the magnetic specific heat, Cm(T), released at TR decreases by increasing x. This means the canting angle of spins from the [111] direction decreases by the substitution of Fe atoms with Co atoms, based on the magnetic structure model of Fe2MnSi proposed by Miles et al. For compounds with 0.5 ≤ x , CP(T) in the low-T range can be reproduced by Debye T3 law. The electronic specific heat coefficient decreases monotonically with x.

  19. The impact of a 2 X CO2 climate on lightning-caused fires

    NASA Technical Reports Server (NTRS)

    Price, Colin; Rind, David

    1994-01-01

    Future climate change could have significant repercussions for lightning-caused wildfires. Two empirical fire models are presented relating the frequency of lightning fires and the area burned by these fires to the effective precipitation and the frequency of thunderstorm activity. One model deals with the seasonal variations in lightning fires, while the second model deals with the interannual variations of lightning fires. These fire models are then used with the Goddard Institute for Space Studies General Circulation Model to investigate possible changes in fire frequency and area burned in a 2 X CO2 climate. In the United States, the annual mean number of lightning fires increases by 44%, while the area burned increases by 78%. On a global scale, the largest increase in lightning fires can be expected in untouched tropical ecosystems where few natural fires occur today.

  20. Apparent critical phenomena in the superionic phase transition of Cu2-xSe

    DOE PAGES

    Kang, Stephen Dongmin; Danilkin, Sergey A.; Aydemir, Umut; ...

    2016-01-11

    The superionic phase transition ofmore » $${\\mathrm{Cu}}_{2-x}\\mathrm{Se}$$ accompanies drastic changes in transport properties. The Seebeck coefficient increases sharply while the electrical conductivity and thermal diffusivity drops. Such behavior has previously been attributed to critical phenomena under the assumption of a continuous phase transition. However, applying Landau's criteria suggests that the transition should be first order. Using the phase diagram that is consistent with a first order transition, we show that the observed transport properties and heat capacity curves can be accounted for and modeled with good agreement. The apparent critical phenomena is shown to be a result of compositional degree-of-freedom. In conclusion, understanding of the phase transition allows to explain the enhancement in the thermoelectric figure-of-merit that is accompanied with the transition.« less

  1. Turbine Design and Analysis for the J-2X Engine Turbopumps

    NASA Technical Reports Server (NTRS)

    Marcu, Bogdan; Tran, Ken; Dorney, Daniel J.; Schmauch, Preston

    2008-01-01

    Pratt and Whitney Rocketdyne and NASA Marshall Space Flight Center are developing the advanced upper stage J-2X engine based on the legacy design of the J-2/J-2S family of engines which powered the Apollo missions. The cryogenic propellant turbopumps have been denoted as Mark72-F and Mark72-0 for the fuel and oxidizer side, respectively. Special attention is focused on preserving the essential flight-proven design features while adapting the design to the new turbopump configuration. Advanced 3-D CFD analysis has been employed to verify turbine aero performance at current flow regime boundary conditions and to mitigate risks associated with stresses. A limited amount of redesign and overall configuration modifications allow for a robust design with performance level matching or exceeding requirement.

  2. Phase Competition and Superconductivity in κ-(BEDT-TTF)2X: Importance of Intermolecular Coulomb Interactions

    NASA Astrophysics Data System (ADS)

    Watanabe, Hiroshi; Seo, Hitoshi; Yunoki, Seiji

    2017-03-01

    We theoretically study the competition among different electronic phases in molecular conductors κ-(BEDT-TTF)2X. The ground-state properties of a 3/4-filled extended Hubbard model with the κ-type geometry are investigated by a variational Monte Carlo method. We find various competing phases: dimer-Mott insulator, polar charge-ordered insulator, 3-fold charge-ordered metal, and superconductivity, whose pairing symmetry is an "extended-s + dx2 - y2"-wave type. Our results show that the superconducting phase is stabilized not on the verge of the Mott metal-insulator transition but near charge order instabilities, clearly indicating the importance of the intradimer charge degree of freedom and the intermolecular Coulomb interactions, beyond the simple description of the half-filled Hubbard model.

  3. [How I explore the various statistical facets of 2 x 2 tables in medicine].

    PubMed

    Albert, A

    2013-09-01

    In the medical scientific literature, 2 x 2 contingency tables are widely used to display the distribution of binary data. They are associated with the definition of basic concepts in medicine and epidemiology that are universally utilized. They are usually taught in any basic course in biostatistics early in the medical curriculum; their interpretation however is not always straightforward. We have discerned at least eight different facets of such fourfold tables: homogeneity test, independence test, McNemar test, Cohen kappa coefficient, incidence relative risk, prevalence relative risk, odds ratio, diagnostic value of a clinical test. Each facet is illustrated by a clinical problem used as an example. This article should help the reader to understand which table he/she is actually dealing with.

  4. Magnetic properties of Co2-xCux(OH)PO4 (x=0, 1 and 2)

    NASA Astrophysics Data System (ADS)

    de Pedro, I.; Jubera, V.; Rojo, J. M.; Lezama, L.; Sánchez Marcos, J.; Rodríguez Fernández, J.; Mesa, J. L.; Rojo, T.; Arriortua, M. I.

    2004-05-01

    The isostructural Co2-xCux(OH)PO4 (x=0, 1 and 2) phases have been prepared from hydrothermal synthesis and characterized from powder X-ray diffraction. The structure consists of a three-dimensional framework in which M(1)O5-trigonal bipyramid dimers and M(2)O6-octahedral chains are simultaneously present. Magnetization measurements of Co2(OH)(PO4) show the existence of two maxima attributed to a three-dimensional antiferromagnetic ordering at 70K and a spin-glass-like state at 12K. When Co2+ is substituted by Cu2+ions, the spin-glass behavior disappears and the magnetic order is decreased.

  5. The impact of a 2 x CO{sub 2} climate on lightning-caused fires

    SciTech Connect

    Price, C.; Rind, D.

    1994-10-01

    Future climate change could have significant repercussions for lightning-caused wildfires. Two empirical fire models are presented relating the frequency of lightning fires and the area burned by these fires to the effective precipitation and the frequency of thunderstorm activity. One model deals with the seasonal variations in lightning fires, while the second model deals with the interannual variations of lightning fires. These fire models are then used with the Goddard Institute for Space Studies General Circulation Model to investigate possible changes in fire frequency and area burned in a 2 x CO{sub 2} climate. In the United States, the annual mean number of lightning fires increases by 44%, while the area burned increases by 78%. On a global scale, the largest increase in lightning fires can be expected in untouched tropical ecosystems where few natural fires occur today. 44 refs., 8 figs., 3 tabs.

  6. Implicit Large Eddy Simulation of a wingtip vortex at Rec =1.2x106

    NASA Astrophysics Data System (ADS)

    Lombard, Jean-Eloi; Moxey, Dave; Sherwin, Spencer; SherwinLab Team

    2015-11-01

    We present recent developments in numerical methods for performing a Large Eddy Simulation (LES) of the formation and evolution of a wingtip vortex. The development of these vortices in the near wake, in combination with the large Reynolds numbers present in these cases, make these types of test cases particularly challenging to investigate numerically. To demonstrate the method's viability, we present results from numerical simulations of flow over a NACA 0012 profile wingtip at Rec = 1.2 x106 and compare them against experimental data, which is to date the highest Reynolds number achieved for a LES that has been correlated with experiments for this test case. Our model correlates favorably with experiment, both for the characteristic jetting in the primary vortex and pressure distribution on the wing surface. The proposed method is of general interest for the modeling of transitioning vortex dominated flows over complex geometries. McLaren Racing/Royal Academy of Engineering Research Chair.

  7. Finite mass enhancement across bandwidth controlled Mott transition in NiS2-xSex

    NASA Astrophysics Data System (ADS)

    Han, Garam; Kyung, W. S.; Kim, Y. K.; Cheng, C. M.; Tsuei, K. D.; Lee, K. D.; Hur, N.; Kim, H.-D.; Kim, C.

    One of the most important and still debated issues in the strongly correlated electron systems is on the metal insulator transition (MIT) mechanism. In the bandwidth controlled Mott transition (BCMT) scenario, which Mott originally proposed, MIT occurs through a mass divergence in which the effective mass of the quasi-particle (QP) diverges approaching the MIT. The interpretation is supported by dynamic mean field theory (DMFT) model calculations. However, few direct observations have been made yet due to various experimental restrictions. In this talk, I present systematic angle resolved photoemission studies on the MIT in NiS2-xSex, which is a well-known BCMT material. We observed not only the bandwidth shrinkage but also the coherent quasi-particle peak (QP) which is not of the surface origin. In addition, we experimentally showed the mass of the QP remains finite approaching the MIT. This work was supported by IBS-R009-D1.

  8. Effects of charge inhomogeneities on elementary excitations in La2-xSrxCuO₄

    DOE PAGES

    Park, S. R.; Hamann, A.; Pintschovius, L.; ...

    2011-12-12

    Purely local experimental probes of many copper oxide superconductors show that their electronic states are inhomogeneous in real space. For example, scanning tunneling spectroscopic imaging shows strong variations in real space, and according to nuclear quadrupole resonance (NQR) studies, the charge distribution in the bulk varies on the nanoscale. However, the analysis of the experimental results utilizing spatially averaged probes often ignores this fact. We have performed a detailed investigation of the doping dependence of the energy and linewidth of the zone-boundary Cu-O bond-stretching vibration in La2-xSrxCuO₄ by inelastic neutron scattering. Both our results as well as previously reported angle-dependentmore » momentum widths of the electronic spectral function detected by angle-resolved photoemission can be reproduced by including the same distribution of local environments extracted from the NQR analysis.« less

  9. Local structure of CuxZn2-xTiO4 inverse spinel

    NASA Astrophysics Data System (ADS)

    Ruiz-Fuertes, J.; Bernert, T.; He, M.; Winkler, B.; Vinograd, V. L.; Milman, V.

    2014-08-01

    Structural and vibrational changes due to the incorporation of Cu in the CuxZn2-xTiO4 inverse spinel solid solution have been investigated by X-ray diffraction, Raman spectroscopy, and ab initio calculations. Both X-ray diffraction and Raman spectroscopy show that the structure remains cubic while the unit-cell volume decreases on Cu2+ incorporation. The compositional dependencies of the Raman frequencies and linewidths indicate the incorporation of Cu2+ into tetrahedral sites. The A1g tetrahedral mode frequency becomes independent on composition for x > 0.6. This is attributed to the limited incorporation of Cu2+ in the tetrahedral sites at Cu-rich compositions. Ab initio calculations with quasi-random structures reveal only a slight energetic preference of Cu2+ for octahedral over tetrahedral sites.

  10. The Dynamic Behavior of the P2X4 Ion Channel in the Closed Conformation.

    PubMed

    Pierdominici-Sottile, Gustavo; Moffatt, Luciano; Palma, Juliana

    2016-12-20

    We present the results of a detailed molecular dynamics study of the closed form of the P2X4 receptor. The fluctuations observed in the simulations were compared with the changes that occur in the transition from the closed to the open structure. To get further insight on the opening mechanism, the actual displacements were decomposed into interchain motions and intrachain deformations. This analysis revealed that the iris-like expansion of the transmembrane helices mainly results from interchain motions that already take place in the closed conformation. However, these movements cannot reach the amplitude required for the opening of the channel because they are impeded by interactions occurring around the ATP binding pocket. This suggests that the union of ATP produces distortions in the chains that eliminate the restrictions on the interchain displacements, leading to the opening of the pore.

  11. Phase diagram and thermal expansion measurements on the system URu2-xFexSi2.

    PubMed

    Ran, Sheng; Wolowiec, Christian T; Jeon, Inho; Pouse, Naveen; Kanchanavatee, Noravee; White, Benjamin D; Huang, Kevin; Martien, Dinesh; DaPron, Tyler; Snow, David; Williamsen, Mark; Spagna, Stefano; Riseborough, Peter S; Maple, M Brian

    2016-11-22

    Thermal expansion, electrical resistivity, magnetization, and specific heat measurements were performed on URu2-xFexSi2 single crystals for various values of Fe concentration x in both the hidden-order (HO) and large-moment antiferromagnetic (LMAFM) regions of the phase diagram. Our results show that the paramagnetic (PM) to HO and LMAFM phase transitions are manifested differently in the thermal expansion coefficient. The uniaxial pressure derivatives of the HO/LMAFM transition temperature T0 change dramatically when crossing from the HO to the LMAFM phase. The energy gap also changes consistently when crossing the phase boundary. In addition, for Fe concentrations at xc ≈ 0.1, we observe two features in the thermal expansion upon cooling, one that appears to be associated with the transition from the PM to the HO phase and another one at lower temperature that may be due to the transition from the HO to the LMAFM phase.

  12. Effects of charge inhomogeneities on elementary excitations in La2-xSrxCuO4

    NASA Astrophysics Data System (ADS)

    Park, S. R.; Hamann, A.; Pintschovius, L.; Lamago, D.; Khaliullin, G.; Fujita, M.; Yamada, K.; Gu, G. D.; Tranquada, J. M.; Reznik, D.

    2011-12-01

    Purely local experimental probes of many copper oxide superconductors show that their electronic states are inhomogeneous in real space. For example, scanning tunneling spectroscopic imaging shows strong variations in real space, and according to nuclear quadrupole resonance (NQR) studies, the charge distribution in the bulk varies on the nanoscale. However, the analysis of the experimental results utilizing spatially averaged probes often ignores this fact. We have performed a detailed investigation of the doping dependence of the energy and linewidth of the zone-boundary Cu-O bond-stretching vibration in La2-xSrxCuO4 by inelastic neutron scattering. Both our results as well as previously reported angle-dependent momentum widths of the electronic spectral function detected by angle-resolved photoemission can be reproduced by including the same distribution of local environments extracted from the NQR analysis.

  13. Manipulating stripes in La2-x Ba x CuO 4 in extreme environments

    NASA Astrophysics Data System (ADS)

    Huecker, Markus; Gu, Genda; Xu, Zhijun; Wen, Jinsheng; Tranquada, John M.; von Zimmermann, Martin

    2011-03-01

    Competing magnetic and electronic interactions in the copper-oxide high temperature superconductors often result in nanoscale inhomogeneity of the charge and spin density. Such observations motivated a proposal that dynamic electronic inhomogeneities are intrinsic to the copper-oxide planes, and can result in electronic states that break their four-fold symmetry. We have performed high-energy single-crystal X-ray diffraction in high magnetic fields and at high pressure to show that the charge and spin stripe phase in La 2-x Ba x Cu O4 constitutes such a state. In particular, our results provide strong evidence that charge stripe correlations in the cuprates are electronically driven and are enhanced within vortices. The work at Brookhaven was supported by the Office of Science, U.S. Department of Energy under Contract No. DE-AC02-98CH10886.

  14. Credit WCT. Original 2"' x 21A" color negative is housed ...

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

    Credit WCT. Original 2-"' x 2-1A" color negative is housed in the JPL Photography Laboratory, Pasadena, California. This view shows the remote charge trimmer, a vertical lathe for turning propellant castings ("grain") in the front room of this structure. Ron Wright is shown in charge of the procedure; the hoist operator is unidentified. Grain for a BATES (Ballistic And Test Evaluation System) motor is being lowered into the lathe with a hoist and specially designed BATES fitting. The spout and waste barrel, in the foreground, collects waste trimmings for disposal (JPL negative no. JPL10286BC, 27 January 1989) - Jet Propulsion Laboratory Edwards Facility, Preparation Building, Edwards Air Force Base, Boron, Kern County, CA

  15. Mechanochemical synthesis of high thermoelectric performance bulk Cu2X (X = S, Se) materials

    NASA Astrophysics Data System (ADS)

    Yang, Dongwang; Su, Xianli; Yan, Yonggao; He, Jian; Uher, Ctirad; Tang, Xinfeng

    2016-11-01

    We devised a single-step mechanochemical synthesis/densification procedure for Cu2X (X = S, Se) thermoelectric materials via applying a pressure of 3 GPa to a stoichiometric admixture of elemental Cu and X for 3 min at room temperature. The obtained bulk materials were single-phase, nearly stoichiometric structures with a relative packing density of 97% or higher. The structures contained high concentration of atomic scale defects and pores of 20-200 nm diameter. The above attributes gave rise to a high thermoelectric performance: at 873 K, the ZT value of Cu2S reached 1.07, about 2.1 times the value typical of samples grown from the melt. The ZT value of Cu2Se samples reached in excess of 1.2, close to the state-of-the-art value.

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

    PubMed

    Sluyter, Ronald

    2015-01-01

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

  17. Nondestructive Evaluation of the J-2X Direct Metal Laser Sintered Gas Generator Discharge Duct

    NASA Technical Reports Server (NTRS)

    Esther, Elizabeth A.; Beshears, Ronald D.; Lash, Rhonda K.

    2012-01-01

    The J-2X program at NASA's Marshall Space Flight Center (MSFC) procured a direct metal laser sintered (DMLS) gas generator discharge duct from Pratt & Whitney Rocketdyne and Morris Technologies for a test program that would evaluate the material properties and durability of the duct in an engine-like environment. DMLS technology was pursued as a manufacturing alternative to traditional techniques, which used off nominal practices to manufacture the gas generator duct's 180 degree turn geometry. MSFC's Nondestructive Evaluation (NDE) Team performed radiographic, ultrasonic, computed tomographic, and fluorescent penetrant examinations of the duct. Results from the NDE examinations reveal some shallow porosity but no major defects in the as-manufactured material. NDE examinations were also performed after hot-fire testing the gas generator duct and yielded similar results pre and post-test and showed no flaw growth or development.

  18. Electron energy loss spectroscopy study of Sr2-xGdxTiMnO6

    NASA Astrophysics Data System (ADS)

    Biskup, Nevenko; Alvarez-Serrano, Inmaculada; Veiga, Maria Luisa; Garcia-Hernandez, Mar; Lopez, Maria Luisa; Varela, Maria

    2012-02-01

    The newly synthesized double perovskite family Sr2-xGdxTiMnO6 (0

  19. NMR investigation of antiferromagnetism and coherence in URu2Si2 -xPx

    NASA Astrophysics Data System (ADS)

    Shirer, K. R.; Lawson, M.; Kissikov, T.; Bush, B. T.; Gallagher, A.; Chen, K.-W.; Baumbach, R. E.; Curro, N. J.

    2017-01-01

    We report 31P and 29Si NMR in single crystals of URu2Si2 -xPx for x =0.09 and x =0.33 . The spectra in the x =0.33 sample are consistent with a homogenous commensurate antiferromagnetic phase below TN˜37 K. The Knight shift exhibits an anomaly at the coherence temperature T* that is slightly enhanced with P doping. Spin-lattice-relaxation rate data indicate that the density of states is suppressed for x =0.09 below 30 K, similar to the undoped compound, but there is no evidence of long-range order at this concentration. Our results suggest that Si substitution provides chemical pressure and electronic tuning mediated by filling of the s /p shells with minimal electronic inhomogeneity.

  20. Inhibition of Streptococcus pneumoniae penicillin-binding protein 2x and Actinomadura R39 DD-peptidase activities by ceftaroline.

    PubMed

    Zervosen, Astrid; Zapun, André; Frère, Jean-Marie

    2013-01-01

    Although the rate of acylation of a penicillin-resistant form of Streptococcus pneumoniae penicillin-binding protein 2x (PBP2x) by ceftaroline is 80-fold lower than that of its penicillin-sensitive counterpart, it remains sufficiently high (k(2)/K = 12,600 M(-1) s(-1)) to explain the sensitivity of the penicillin-resistant strain to this new cephalosporin. Surprisingly, the Actinomadura R39 DD-peptidase is not very sensitive to ceftaroline.

  1. Plasmonic Cu(2-x)S nanocrystals: optical and structural properties of copper-deficient copper(I) sulfides.

    PubMed

    Zhao, Yixin; Pan, Hongcheng; Lou, Yongbing; Qiu, Xiaofeng; Zhu, JunJie; Burda, Clemens

    2009-04-01

    Cu(2-x)S (x = 1, 0.2, 0.03) nanocrystals were synthesized with three different chemical methods: sonoelectrochemical, hydrothermal, and solventless thermolysis methods in order to compare their common optical and structural properties. The compositions of the Cu(2-x)S nanocrystals were varied from CuS (covellite) to Cu(1.97)S (djurleite) through adjusting the reduction potential in the sonoelectrochemical method, adjusting the pH value in the hydrothermal method and by choosing different precursor pretreatments in the solventless thermolysis approach, respectively. The crystallinity and morphology of the products were characterized by X-ray diffraction (XRD) and transmission electron microscopy (TEM), which shows that most of them might be of pure stoichiometries but some of them are mixtures. The obtained XRDs were studied in comparison to the XRD patterns of previously reported Cu(2-x)S. We found consistently that under ambient conditions the copper deficient Cu(1.97)S (djurleite) is more stable than Cu(2)S (chalcocite). Corroborated by recent computational studies by Lambrecht et al. and experimental work by Alivisatos et al. This may be the reason behind the traditionally known instability of the bulk Cu(2)S/CdS interface. Both Cu(2)S and the copper-deficient Cu(1.97)S have very similar but distinguishable electronic and crystal structure. The optical properties of these Cu(2-x)S NCs were characterized by UV-vis spectroscopy and NIR. All presented Cu(2-x)S NCs show a blue shift in the band gap absorption compared to bulk Cu(2-x)S. Moreover the spectra of these Cu(2-x)S NCs indicate direct band gap character based on their oscillator strengths, different from previously reported experimental results. The NIR spectra of these Cu(2-x)S NCs show a carrier concentration dependent plasmonic absorption.

  2. Macrophage P2X7 Receptor Function Is Reduced during Schistosomiasis: Putative Role of TGF-β1

    PubMed Central

    Oliveira, Suellen D'arc Santos; Nanini, Hayandra Ferreira; Savio, Luiz Eduardo Baggio; Waghabi, Mariana Caldas; Silva, Claudia Lucia Martins

    2014-01-01

    Schistosomiasis is a chronic inflammatory disease whose macrophages are involved in immunopathology modulation. Although P2X7 receptor signaling plays an important role in inflammatory responses mediated by macrophages, no reports have examined the role of P2X7 receptors in macrophage function during schistosomiasis. Thus, we evaluated P2X7 receptor function in peritoneal macrophages during schistosomiasis using an ATP-induced permeabilization assay and measurements of the intracellular Ca2+ concentration. ATP treatment induced significantly less permeabilization in macrophages from S. mansoni-infected mice than in control cells from uninfected animals. Furthermore, P2X7-mediated increases in intracellular Ca2+ levels were also reduced in macrophages from infected mice. TGF-β1 levels were increased in the peritoneal cavity of infected animals, and pretreatment of control macrophages with TGF-β1 reduced ATP-induced permeabilization, mimicking the effect of S. mansoni infection. Western blot and qRT-PCR data showed no difference in P2X7 protein and mRNA between uninfected, infected, and TGF-β1-treated groups. However, immunofluorescence analysis revealed reduced cell surface localization of P2X7 receptors in macrophages from infected and TGF-β1-treated mice compared to controls. Therefore, our data suggest that schistosomiasis reduces peritoneal macrophage P2X7 receptor signaling. This effect is likely due to the fact that infected mice have increased levels of TGF-β1, which reduces P2X7 receptor cell surface expression. PMID:25276050

  3. Development of a Small Molecule P2X7R Antagonist as a Treatment for Acute SCI

    DTIC Science & Technology

    2011-10-01

    impact of deletion of connexins (Cx30/Cx43) in astrocytes on post-traumatic ATP release. In vivo bioluminescence imaging showed a significant reduction...the observation that ATP release and activation of P2X7 receptors drives the innate inflammatory response initiated by spinal cord injury. P2X7R...swelling. Prior studies have shown that excessive ATP release from peri-traumatic regions contributes to the inflammatory response to SCI by

  4. Using Decision Trees to Detect and Isolate Simulated Leaks in the J-2X Rocket Engine

    NASA Technical Reports Server (NTRS)

    Schwabacher, Mark A.; Aguilar, Robert; Figueroa, Fernando F.

    2009-01-01

    The goal of this work was to use data-driven methods to automatically detect and isolate faults in the J-2X rocket engine. It was decided to use decision trees, since they tend to be easier to interpret than other data-driven methods. The decision tree algorithm automatically "learns" a decision tree by performing a search through the space of possible decision trees to find one that fits the training data. The particular decision tree algorithm used is known as C4.5. Simulated J-2X data from a high-fidelity simulator developed at Pratt & Whitney Rocketdyne and known as the Detailed Real-Time Model (DRTM) was used to "train" and test the decision tree. Fifty-six DRTM simulations were performed for this purpose, with different leak sizes, different leak locations, and different times of leak onset. To make the simulations as realistic as possible, they included simulated sensor noise, and included a gradual degradation in both fuel and oxidizer turbine efficiency. A decision tree was trained using 11 of these simulations, and tested using the remaining 45 simulations. In the training phase, the C4.5 algorithm was provided with labeled examples of data from nominal operation and data including leaks in each leak location. From the data, it "learned" a decision tree that can classify unseen data as having no leak or having a leak in one of the five leak locations. In the test phase, the decision tree produced very low false alarm rates and low missed detection rates on the unseen data. It had very good fault isolation rates for three of the five simulated leak locations, but it tended to confuse the remaining two locations, perhaps because a large leak at one of these two locations can look very similar to a small leak at the other location.

  5. Ground States of Random Spanning Trees on a D-Wave 2X

    NASA Astrophysics Data System (ADS)

    Hall, J. S.; Hobl, L.; Novotny, M. A.; Michielsen, Kristel

    The performances of two D-Wave 2 machines (476 and 496 qubits) and of a 1097-qubit D-Wave 2X were investigated. Each chip has a Chimera interaction graph calG . Problem input consists of values for the fields hj and for the two-qubit interactions Ji , j of an Ising spin-glass problem formulated on calG . Output is returned in terms of a spin configuration {sj } , with sj = +/- 1 . We generated random spanning trees (RSTs) uniformly distributed over all spanning trees of calG . On the 476-qubit D-Wave 2, RSTs were generated on the full chip with Ji , j = - 1 and hj = 0 and solved one thousand times. The distribution of solution energies and the average magnetization of each qubit were determined. On both the 476- and 1097-qubit machines, four identical spanning trees were generated on each quadrant of the chip. The statistical independence of these regions was investigated. In another study, on the D-Wave 2X, one hundred RSTs with random Ji , j ∈ { - 1 , 1 } and hj = 0 were generated on the full chip. Each RST problem was solved one hundred times and the number of times the ground state energy was found was recorded. This procedure was repeated for square subgraphs, with dimensions ranging from 7 ×7 to 11 ×11. Supported in part by NSF Grants DGE-0947419 and DMR-1206233. D-Wave time provided by D-Wave Systems and by the USRA Quantum Artificial Intelligence Laboratory Research Opportunity.

  6. Thermoelectric properties of Mg2X (X = Si, Ge) based bulk and quantum well systems

    NASA Astrophysics Data System (ADS)

    Yelgel, Övgü Ceyda

    2017-01-01

    Mg2X (X = Si, Ge) compounds are promising thermoelectric materials for middle temperature applications due to good thermoelectric properties, nontoxicity, and abundantly available constituent elements. So far, these materials used in applications have all been in bulk form. Herein we report a full theory of thermoelectric transport properties of 3D bulk and 2D quantum well systems. The main aim of this present work is to show the effect of quantum confinement on the enhancement of the thermoelectric figure of merit theoretically. Results are given for n-type Mg2 Si0.5 Ge0.5 solid solutions and n-type Mg2Si/Mg2Ge/Mg2Si quantum well systems where the values of well widths are taken as 10 nm, 15 nm, and 20 nm, respectively. The n-type doping is made by using Sb- and La-elements as dopants. Experimental results for solid solutions are included to provide demonstration of proof of principle for the theoretical model applied for 3D bulk structures. The maximum thermoelectric figure of merits of Lax Mg2 -x Si0.49 Ge0.5 Sb0.01 solid solutions are obtained to be 0.64 and 0.56 at 800 K for x = 0 and x = 0.01 sample, respectively. While, at the same temperature, due to the relatively low phonon thermal conductivity the state-of-the-art ZT values of 2.41 and 2.26 have been attained in the Mg2Si/Mg2Ge/Mg2Si quantum well samples with 0.01 wt. % Sb-doped and 0.01 wt. % Sb- and 0.01 wt. % La-doped, respectively.

  7. The J-2X Upper Stage Engine: From Design to Hardware

    NASA Technical Reports Server (NTRS)

    Byrd, Thomas

    2010-01-01

    NASA is well on its way toward developing a new generation of launch vehicles to support of national space policy to retire the Space Shuttle fleet, complete the International Space Station, and return to the Moon as the first step in resuming this nation s exploration of deep space. The Constellation Program is developing the launch vehicles, spacecraft, surface systems, and ground systems to support those plans. Two launch vehicles will support those ambitious plans the Ares I and Ares V. (Figure 1) The J-2X Upper Stage Engine is a critical element of both of these new launchers. This paper will provide an overview of the J-2X design background, progress to date in design, testing, and manufacturing. The Ares I crew launch vehicle will lift the Orion crew exploration vehicle and up to four astronauts into low Earth orbit (LEO) to rendezvous with the space station or the first leg of mission to the Moon. The Ares V cargo launch vehicle is designed to lift a lunar lander into Earth orbit where it will be docked with the Orion spacecraft, and provide the thrust for the trans-lunar journey. While these vehicles bear some visual resemblance to the 1960s-era Saturn vehicles that carried astronauts to the Moon, the Ares vehicles are designed to carry more crew and more cargo to more places to carry out more ambitious tasks than the vehicles they succeed. The government/industry team designing the Ares rockets is mining a rich history of technology and expertise from the Shuttle, Saturn and other programs and seeking commonality where feasible between the Ares crew and cargo rockets as a way to minimize risk, shorten development times, and live within the budget constraints of its original guidance.

  8. Secondary Structure and Gating Rearrangements of Transmembrane Segments in Rat P2X4 Receptor Channels

    PubMed Central

    Silberberg, Shai D.; Chang, Tsg-Hui; Swartz, Kenton J.

    2005-01-01

    P2X receptors are cation selective channels that are activated by extracellular nucleotides. These channels are likely formed by three identical or related subunits, each having two transmembrane segments (TM1 and TM2). To identify regions that undergo rearrangement during gating and to probe their secondary structure, we performed tryptophan scanning mutagenesis on the two putative TMs of the rat P2X4 receptor channel. Mutant channels were expressed in Xenopus oocytes, concentration–response relationships constructed for ATP, and the EC50 estimated by fitting the Hill equation to the data. Of the 22 mutations in TM1 and 24 in TM2, all but one in TM1 and seven in TM2 result in functional channels. Interestingly, the majority of the functional mutants display an increased sensitivity to ATP, and in general these perturbations are more pronounced for TM2 when compared with TM1. For TM1 and for the outer half of TM2, the perturbations are consistent with these regions adopting α-helical secondary structures. In addition, the greatest perturbations in the gating equilibrium occur for mutations near the outer ends of both TM1 and TM2. Surface biotinylation experiments reveal that all the nonfunctional mutants traffic to the surface membrane at levels comparable to the WT channel, suggesting that these mutations likely disrupt ion conduction or gating. Taken together, these results suggest that the outer parts of TM1 and TM2 are helical and that they move during activation. The observation that the majority of nonconducting mutations are clustered toward the inner end of TM2 suggests a critical functional role for this region. PMID:15795310

  9. Analyses of Longitudinal Mode Combustion Instability in J-2X Gas Generator Development

    NASA Technical Reports Server (NTRS)

    Hulka, J. R.; Protz, C. S.; Casiano, M. J.; Kenny, R. J.

    2011-01-01

    The National Aeronautics and Space Administration (NASA) and Pratt & Whitney Rocketdyne are developing a liquid oxygen/liquid hydrogen rocket engine for future upper stage and trans-lunar applications. This engine, designated the J-2X, is a higher pressure, higher thrust variant of the Apollo-era J-2 engine. The contract for development was let to Pratt & Whitney Rocketdyne in 2006. Over the past several years, development of the gas generator for the J-2X engine has progressed through a variety of workhorse injector, chamber, and feed system configurations on the component test stand at the NASA Marshall Space Flight Center (MSFC). Several of the initial configurations resulted in combustion instability of the workhorse gas generator assembly at a frequency near the first longitudinal mode of the combustion chamber. In this paper, several aspects of these combustion instabilities are discussed, including injector, combustion chamber, feed system, and nozzle influences. To ensure elimination of the instabilities at the engine level, and to understand the stability margin, the gas generator system has been modeled at the NASA MSFC with two techniques, the Rocket Combustor Interaction Design and Analysis (ROCCID) code and a lumped-parameter MATLAB(TradeMark) model created as an alternative calculation to the ROCCID methodology. To correctly predict the instability characteristics of all the chamber and injector geometries and test conditions as a whole, several inputs to the submodels in ROCCID and the MATLAB(TradeMark) model were modified. Extensive sensitivity calculations were conducted to determine how to model and anchor a lumped-parameter injector response, and finite-element and acoustic analyses were conducted on several complicated combustion chamber geometries to determine how to model and anchor the chamber response. These modifications and their ramification for future stability analyses of this type are discussed.

  10. Effect of artemisinin on neuropathic pain mediated by P2X4 receptor in dorsal root ganglia.

    PubMed

    Ying, Mofeng; Liu, Hui; Zhang, Tengling; Jiang, Chenxu; Gong, Yingxin; Wu, Bing; Zou, Lifang; Yi, Zhihua; Rao, Shenqiang; Li, Guilin; Zhang, Chunping; Jia, Tianyu; Zhao, Shanhong; Yuan, Huilong; Shi, Liran; Li, Lin; Liang, Shangdong; Liu, Shuangmei

    2017-02-09

    Neuropathic pain is a type of chronic pain caused by nervous system damage and dysfunction. The pathogenesis of chronic pain is complicated, and there are no effective therapies for neuropathic pain. Studies show that the P2X4 receptor expressed in the satellite glial cells (SGCs) of dorsal root ganglia (DRG) is related to neuropathic pain. Artemisinin is a monomeric component extracted from traditional Chinese medicine and has a variety of important pharmacological effects and potential applications. This study observed the effect of artemisinin on neuropathic pain and delineated its possible mechanism. The chronic constriction injury (CCI) rat model was used in this study. The results demonstrated that artemisinin relieved pain behaviors in the CCI rats, inhibited the expression of P2X4 receptor in the DRG, and decreased the ATP-activated currents in HEK293 cells transfected with P2X4 plasmid. Dual-labeling immunofluorescence showed that the coexpression of P2X4 receptor and glial fibrillary acidic protein (GFAP) in the DRG of CCI rats was increased compared to control rats. After CCI rats were treated with artemisinin, the coexpression of P2X4 receptor and GFAP in the DRG was significantly decreased compared to the CCI group. This finding suggested that artemisinin could inhibit the nociceptive transmission mediated by P2X4 receptor in the DRG SGCs and thus relieve pain behaviors in the CCI rats.

  11. Silencing P2X7 receptor downregulates the expression of TCP-1 involved in lymphoma lymphatic metastasis.

    PubMed

    Jiang, Xudong; Mao, Wenjuan; Yang, Ziyi; Zeng, Jia; Zhang, Yi; Song, Yang; Kong, Ying; Ren, Shuangyi; Zuo, Yunfei

    2015-12-08

    P2X7R is an ATP-gated cation channel that participates in cell proliferation and apoptosis. TCP-1 assists with the protein folding. According to our previous research, the P2X7R has a potential role in P388D1 lymphoid neoplasm cells dissemination to peripheral lymph nodes. In order to make a further exploration about the probable mechanism, the lymph nodes which metastasized by P2X7R-silenced P388D1 cells or non-silenced cells were analyzed by 2DE and a MALDI-TOF-based proteomics approach. In the 64 proteins which were differentially expressed between two groups, TCP-1 was found to be significantly decreased in P2X7R shRNA group compared to controls. This correlation was also found in subsequent experiments in vivo and in vitro. The positive correlation between P2X7R and TCP-1 was also proved in both lymphoma and benign lymphadenopathy tissues from patients. It indicates that TCP-1 may be a crucial downstream molecular of P2X7R and plays a novel role in lymphoid neoplasm metastasis.

  12. Association of IFN-γ and P2X7 Receptor Gene Polymorphisms in Susceptibility to Tuberculosis Among Iranian Patients.

    PubMed

    Shamsi, Mahdi; Zolfaghari, Mohammad Reza; Farnia, Parissa

    2016-03-01

    Interferon-gamma (IFN-γ) and P2X7 receptor are crucial for host defence against mycobacterial infections. Recent studies have indicated that IFN-γ, IFN-γ receptor 1 (IFN-γR1) andP2X7 gene polymorphisms are associated with susceptibility to pulmonary tuberculosis (TB). However, the relationship between IFN-γ and P2X7 polymorphism and TB susceptibility remains inconclusive in Iranian population. For this reason, single nucleotide polymorphisms (SNPs) in IFN-γ (G+2109A), IFN-γR1 (G-611A) and P2X7 genes (at -762, 1513 position) in patients (n = 100) were assessed using PCR-RFLP. Data were analysed with SPSS version 18. For the 2109 loci of IFN-γ gene, the frequency of mutant alleles between patients and controls were not statistically significant. However, there was a significant difference between the TB patient and controls for -611 alleles of IFN-γR1 (P = 0.01). Additionally, the frequency of P2X7 gene polymorphisms (SNP-762 and 1513) between patients and controls was statistically significant. In conclusions, our study revealed a significant association of IFN-γR1 and P2X7 genes polymorphisms with risk of developing TB in Iranian population.

  13. Facile synthesis of rod-like Cu2-xSe and insight into its improved lithium storage property.

    PubMed

    Li, He; Jiang, Jiali; Wang, Feng; Huang, Jianxing; Wang, Yunhui; Zhang, Yiyong; Zhao, Jinbao

    2017-04-06

    A rod-like Cu2-xSe is synthesized via a facile water evaporation process. The electrochemical reaction mechanism is investigated with ex-situ X-ray diffraction (XRD) test. By adopting ether-based electrolyte instead of carbonate-based electrolyte, the electrochemical performance of Cu2-xSe electrodes improves significantly. The Cu2-xSe electrodes exhibit outstanding cycle performance, after 1000 cycles, 160 mAh g-1 can be maintained with the retention of 80.3 %. At current density of 100, 200, 500 and 1000 mA g-1, the capacity of Cu2-xSe/Li battery is 208, 202, 200 and 198 mAh g-1, respectively, showing excellent rate capability. The 4-probe conductivity measurements along with electrochemical impendence spectroscopy (EIS) and cyclic voltammetry (CV) tests illustrate that the Cu2-xSe electrodes display high specific conductivity and impressive lithium ion diffusion rate, which makes the Cu2-xSe to be a promising anode material for lithium ion batteries.

  14. Nickel deficiency in RENi2-xP2 (RE=La, Ce, Pr). Combined crystallographic and physical property studies

    SciTech Connect

    Bauer, Eric D; Ronning, Filip; Thompson, Joe D; Sarrao, John L; Bobev, S; Xia, S

    2008-01-01

    Large single crystals from RENi{sub 2-x}P{sub 2} (RE = La, Ce, Pr) were synthesized from the pure elements using Sn as a metal flux, and their structures were established by X-ray crystallography. The title compounds were confirmed to crystallize in the body-centered tetragonal ThCr{sub 2}Si{sub 2} structure type (space group I4/mmm (No. 139); Pearson's symbol tI10), but with a significant stoichiometry breadth with respect to the transition metal. Systematic synthetic work, coupled with accurate structure refinements indicated strong correlation between the degree of Ni-deficiency and the reaction conditions. For four different PrNi{sub 2-x}P{sub 2} (x {le} 0.5) samples, temperature dependent dc magnetization measurements indicated typical local moment 4f-magnetism and a stable Pr{sup 3+} ground state. Field-dependent heat capacity data confirmed a ferromagnetic order at low temperature, and the variations of T{sub c} with the concentration of Ni defects are discussed. LaNi{sub 2-x}P{sub 2}, as expected was found to be Pauli-like paramagnetic in the studied temperature regime, while the Ce-analog CeNi{sub 2-x}P{sub 2} (x = 0.28(1)) showed the characteristics of a mixed valent Ce{sup 3+}/Ce{sup 4+} system with a possible Kondo temperature on the order of 230 K.

  15. Cathelicidin modulates the function of monocytes/macrophages via the P2X7 receptor in a teleost, Plecoglossus altivelis.

    PubMed

    Li, Chang-Hong; Lu, Xin-Jiang; Li, Ming-Yun; Chen, Jiong

    2015-12-01

    Cathelicidins (CATHs) are a family of endogenous antimicrobial peptides that are capable of both direct bacteria-killing and immunomodulatory effects. P2X7 receptor (P2X7R) is a mediator of CATH in mammalian immune cells. Here, we studied the function and regulation of CATH in head kidney-derived monocytes/macrophages (MO/MФ) from ayu, Plecoglossus altivelis. We investigated the chemotaxis of MO/MФ in response to ayu CATH (PaCATH), and found that PaCATH had a dose-dependent effect on MO/MФ chemotaxis with the optimal concentration of 10.0 μg/ml. The qPCR and Western blot analysis revealed that PaCATH inhibited the expression of ayu P2X7R (PaP2X7R) at both mRNA and protein levels. Knockdown of the PaP2X7R expression in ayu MO/MФ by RNA interference not only significantly inhibited the chemotactic effect of PaCATH on MO/MФ, but also obviously reduced the effect of PaCATH on the phagocytosis, bacteria-killing, respiratory burst, and cytokine expression of ayu MO/MФ. Our study revealed that the immunomodulatory effect of fish CATH is mediated by P2X7R.

  16. Electrochromic device

    SciTech Connect

    Schwendemanm, Irina G; Polcyn, Adam D; Finley, James J; Boykin, Cheri M; Knowles, Julianna M

    2011-03-15

    An electrochromic device includes a first substrate spaced from a second substrate. A first conductive member is formed over at least a portion of the first substrate. A first electrochromic material is formed over at least a portion of the first conductive member. The first electrochromic material includes an organic material. A second conductive member is formed over at least a portion of the second substrate. A second electrochromic material is formed over at least a portion of the second conductive member. The second electrochromic material includes an inorganic material. An ionic liquid is positioned between the first electrochromic material and the second electrochromic material.

  17. Device Connectivity

    PubMed Central

    Walsh, John; Roberts, Ruth; Morris, Richard

    2015-01-01

    Patients with diabetes have to take numerous factors/data into their therapeutic decisions in daily life. Connecting the devices they are using by feeding the data generated into a database/app is supposed to help patients to optimize their glycemic control. As this is not established in practice, the different roadblocks have to be discussed to open the road. That large telecommunication companies are now entering this market might be a big help in pushing this forward. Smartphones offer an ideal platform for connectivity solutions. PMID:25614015

  18. Electrooptical Devices.

    DTIC Science & Technology

    1984-09-30

    Table 1-1 10 II-5 Calculated Ij as a Function of the Cap p-Doping 12 III-1 L-I Characteristics of the Five Mass-Transported BH Lasers with Different...343, a = 5.0 /im, W = 1.5 nmy and b = 2.0 pm 9 vni ELECTROOPTICAL DEVICES I. NEW DEVELOPMENTS IN MASS-TRANSPORTED GalnAsP/InP BURIED...HETEROSTRUCTURE LASERS As a potentially very important class of sources in fiber optical communication and inte- grated optics, GalnAsP/InP buried

  19. Electrospray device

    NASA Technical Reports Server (NTRS)

    Demmons, Nathaniel (Inventor); Martin, Roy (Inventor); Hruby, Vladimir (Inventor); Roy, Thomas (Inventor); Spence, Douglas (Inventor); Ehrbar, Eric (Inventor); Zwahlen, Jurg (Inventor)

    2011-01-01

    An electrospray device includes an electrospray emitter adapted to receive electrospray fluid; an extractor plate spaced from the electrospray emitter and having at least one aperture; and a power supply for applying a first voltage between the extractor plate and emitter for generating at least one Taylor cone emission through the aperture to create an electrospray plume from the electrospray fluid, the extractor plate as well as accelerator and shaping plates may include a porous, conductive medium for transporting and storing excess, accumulated electrospray fluid away from the aperture.

  20. Diversionary device

    DOEpatents

    Grubelich, Mark C.

    2001-01-01

    A diversionary device has a housing having at least one opening and containing a non-explosive propellant and a quantity of fine powder packed within the housing, with the powder being located between the propellant and the opening. When the propellant is activated, it has sufficient energy to propel the powder through the opening to produce a cloud of powder outside the housing. An igniter is also provided for igniting the cloud of powder to create a diversionary flash and bang, but at a low enough pressure to avoid injuring nearby people.

  1. OLED devices

    SciTech Connect

    Sapochak, Linda Susan; Burrows, Paul Edward; Bimalchandra, Asanga

    2011-02-22

    An OLED device having an emission layer formed of an ambipolar phosphine oxide host material and a dopant, a hole transport layer in electrical communication with an anode, an electron transport layer in communication with a cathode, wherein the HOMO energy of the hole transport layer is substantially the same as the HOMO energy of the ambipolar host in the emission layer, and the LUMO energy of the electron transport layer is substantially the same as the LUMO energy of the ambipolar host in the emission layer.

  2. Cooling device

    SciTech Connect

    Teske, L.

    1984-02-21

    A cooling device is claimed for coal dust comprising a housing, a motor-driven conveyor system therein to transport the coal dust over coolable trays in the housing and conveyor-wheel arms of spiral curvature for moving the coal dust from one or more inlets to one or more outlets via a series of communicating passages in the trays over which the conveyor-wheel arms pass under actuation of a hydraulic motor mounted above the housing and driving a vertical shaft, to which the conveyor-wheel arms are attached, extending centrally downwardly through the housing.

  3. Electroexplosive device

    NASA Technical Reports Server (NTRS)

    Menichelli, V. J. (Inventor)

    1978-01-01

    An electroexplosive device is presented which employs a header having contact pins hermetically sealed with glass passing through from a connector end of the header to a cavity filled with a shunt layer of a new nonlinear resistive composition and a heat-sink layer of a new dielectric composition having good thermal conductivity and capacity. The nonlinear resistive layer and the heat-sink layer are prepared from materials by mixing with a low temperature polymerizing resin. The resin is dissolved in a suitable solvent and later evaporated. The resultant solid composite is ground into a powder, press formed into the header and cured (polymerized) at about 250 to 300 F.

  4. Distribution of P2Y2 receptors in the guinea pig enteric nervous system and its coexistence with P2X2 and P2X3 receptors, neuropeptide Y, nitric oxide synthase and calretinin.

    PubMed

    Xiang, Zhenghua; Burnstock, Geoffrey

    2005-11-01

    The distribution of P2Y2 receptor-immunoreactive (ir) neurons and fibers and coexistence of P2Y2 with P2X2 and P2X3 receptors, neuropeptide Y (NPY), calretinin (CR), calbindin (CB) and nitric oxide synthase (NOS) was investigated with immunostaining methods. The results showed that P2Y2-ir neurons and fibers were distributed widely in myenteric and submucous plexuses of the guinea pig stomach corpus, jejunum, ileum and colon. The typical morphology of P2Y2-ir neurons was a long process with strong positive staining on the same side of the cell body. The P2Y2-ir neurons could be Dogiel type 1. About 40-60% P2X3-ir neurons were immunoreactive for P2Y2 in the myenteric plexus and all the P2X3-ir neurons expressed the P2Y2 receptor in the submucosal plexus; almost all the NPY-ir neurons and the majority of CR-ir neurons were also immunoreactive for P2Y2, especially in the myenteric plexus of the small intestine; no P2Y2-ir neurons were immunoreactive for P2X2 receptors, CB and NOS. It is shown for the first time that S type/Dogiel type 1 neurons with fast P2X and slow P2Y receptor-mediated depolarizations could be those neurons expressing both P2Y2-ir and P2X3-ir and that they are widely distributed in myenteric and submucosal plexuses of guinea pig gut.

  5. Subunit-specific coupling between gamma-aminobutyric acid type A and P2X2 receptor channels.

    PubMed

    Boué-Grabot, Eric; Toulmé, Estelle; Emerit, Michel B; Garret, Maurice

    2004-12-10

    ATP and gamma-aminobutyric acid (GABA) are two fast neurotransmitters co-released at central synapses, where they co-activate excitatory P2X and inhibitory GABAA (GABA type A) receptors. We report here that co-activation of P2X2 and various GABAA receptors, co-expressed in Xenopus oocytes, leads to a functional cross-inhibition dependent on GABAA subunit composition. Sequential applications of GABA and ATP revealed that alphabeta- or alphabetagamma-containing GABAA receptors inhibited P2X2 channels, whereas P2X2 channels failed to inhibit gamma-containing GABAA receptors. This functional cross-talk is independent of membrane potential, changes in current direction, and calcium. Non-additive responses observed between cation-selective GABAA and P2X2 receptors further indicate the chloride independence of this process. Overexpression of minigenes encoding either the C-terminal fragment of P2X2 or the intracellular loop of the beta3 subunit disrupted the functional cross-inhibition. We previously demonstrated functional and physical cross-talk between rho1 and P2X2 receptors, which induced a retargeting of rho1 channels to surface clusters when co-expressed in hippocampal neurons (Boue-Grabot, E., Emerit, M. B., Toulme, E., Seguela, P., and Garret, M. (2004) J. Biol. Chem. 279, 6967-6975). Co-expression of P2X2 and chimeric rho1 receptors with the C-terminal sequences of alpha2, beta3, or gamma2 subunits indicated that only rho1-beta3 and P2X2 channels exhibit both functional cross-inhibition in Xenopus oocytes and co-clustering/retargeting in hippocampal neurons. Therefore, the C-terminal domain of P2X2 and the intracellular loop of beta GABAA subunits are required for the functional interaction between ATP- and GABA-gated channels. This gamma subunit-dependent cross-talk may contribute to the regulation of synaptic activity.

  6. Atmospheric fate of hydrofluoroolefins, CxF2x+1CHCH2 (x = 1,2,3,4 and 6): Kinetics with Cl atoms and products.

    PubMed

    Ballesteros, Bernabé; Jiménez, Elena; Moreno, Alberto; Soto, Amparo; Antiñolo, María; Albaladejo, José

    2017-01-01

    Rate coefficients for the gas-phase reactions of CxF2x+1CHCH2 (x = 1, 2, 3, 4 and 6) with Cl atoms were determined at (298 ± 2) K and (710 ± 5) Torr of air using a relative rate technique. Two experimental setups with simulation chambers were employed with Fourier Transform Infrared (FTIR) spectroscopy and Gas Chromatography coupled to Mass Spectrometry (GC-MS) as detection techniques. The Cl-rate coefficients obtained were (in 10(-10) cm(3) molecule(-1) s(-1)): (0.85 ± 0.11) for CF3CHCH2, (1.11 ± 0.08) for C2F5CHCH2, (1.12 ± 0.18) for C3F7CHCH2, (0.97 ± 0.09) for C4F9CHCH2, and (0.99 ± 0.08) for C6F13CHCH2. Additionally, the gas-phase products were identified and quantified, when possible, by FTIR spectroscopy or GC-MS. The main reaction product was reported to be CxF2x+1C(O)CH2Cl. The fluorinated species, CxF2x+1CHO and CxF2x+1C(O)CH2Cl, were identified. CF3C(O)CH2Cl and CF3CHO were found to be formed with molar yield of (69 ± 5)% and (9 ± 1)%, respectively. The global lifetime of the investigated CxF2x+1CHCH2 due to their Cl-reaction is more than 100 days so this route does not compete with the removal by OH radicals. This lifetime is long enough for CxF2x+1CHCH2 to be transported to remote areas where they can be degraded. However, at a local scale, in marine regions at dawn the removal of CxF2x+1CHCH2 is expected to occur in ca. 1 day. The atmospheric degradation of these hydrofluoroolefins by Cl atoms is not expected to be a source of bioaccumulative perfluorinated carboxylic acids, CxF2x+1C(O)OH. Additionally, the UV absorption cross sections of CF3C(O)CH2Cl were determined together with the rate coefficient of the OH reaction by an absolute kinetic method at room temperature.

  7. Electrochromic material and electro-optical device using same

    DOEpatents

    Cogan, Stuart F.; Rauh, R. David

    1992-01-01

    An oxidatively coloring electrochromic layer of composition M.sub.y CrO.sub.2+x (0.33.ltoreq.y.ltoreq.2.0 and x.ltoreq.2) where M=Li, Na or K with improved transmittance modulation, improved thermal and environmental stability, and improved resistance to degradation in organic liquid and polymeric electrolytes. The M.sub.y CrO.sub.2+x provides complementary optical modulation to cathodically coloring materials in thin-film electrochromic glazings and electrochromic devices employing polymeric Li.sup.+ ion conductors.

  8. Electrochromic material and electro-optical device using same

    DOEpatents

    Cogan, S.F.; Rauh, R.D.

    1992-01-14

    An oxidatively coloring electrochromic layer of composition M[sub y]CrO[sub 2+x] (0.33[le]y[le]2.0 and x[le]2) where M=Li, Na or K with improved transmittance modulation, improved thermal and environmental stability, and improved resistance to degradation in organic liquid and polymeric electrolytes. The M[sub y]CrO[sub 2+x] provides complementary optical modulation to cathodically coloring materials in thin-film electrochromic glazings and electrochromic devices employing polymeric Li[sup +] ion conductors. 12 figs.

  9. Red, green, blue and white organic electroluminescent devices

    NASA Astrophysics Data System (ADS)

    Tsou, Chuan-Cheng; Lu, Huei-Tzong; Yokoyama, Meiso

    2005-06-01

    Full-color capability is an essential feature in organic electroluminescent (OEL) devices for flat panel display. This work presents novel designs for red, green, blue and white OEL devices. Indium tin oxide (ITO) was used as a glass substrate and N, N'-bis-(1-naphthyl)- N, N'-diphenyl-1,1-biphenyl-4-4'-diamine (NPB) as a hole transport layer (HTL). Bathocuproine (BCP) was used as a hole-blocking layer (HBL), DCM2, as a red fluorescent dye, was doped into the BCP layer. Tris-(8-hydroxy-quinoline) aluminum (Alq 3) was used in the electron transport layer (ETL), and aluminum (Al) was used as a cathode in OEL devices with the configuration ITO/NPB (30 nm)/BCP:DCM2 ( x%, 30 nm)/Alq 3 (40 nm)/Al. A green OEL device is obtained by employing this structure without a BCP:DCM2 ( x %) layer; a blue OEL device is obtained by using a BCP layer without the DCM2 dopant. The red OEL device is obtained by doping 10% DCM2 in the BCP layer. The white OEL device is produced by doping 1% DCM2 in the BCP layer. The CIE x and y coordinates of the white OEL device are 0.32 and 0.32, respectively.

  10. Shockwaves induce osteogenic differentiation of human mesenchymal stem cells through ATP release and activation of P2X7 receptors.

    PubMed

    Sun, Dahui; Junger, Wolfgang G; Yuan, Changji; Zhang, Wenyan; Bao, Yi; Qin, Daming; Wang, Chengxue; Tan, Lei; Qi, Baochang; Zhu, Dong; Zhang, Xizheng; Yu, Tiecheng

    2013-06-01

    Shockwave treatment promotes bone healing of nonunion fractures. In this study, we investigated whether this effect could be due to adenosine 5'-triphosphate (ATP) release-induced differentiation of human mesenchymal stem cells (hMSCs) into osteoprogenitor cells. Cultured bone marrow-derived hMSCs were subjected to shockwave treatment and ATP release was assessed. Osteogenic differentiation and mineralization of hMSCs were evaluated by examining alkaline phosphatase activity, osteocalcin production, and calcium nodule formation. Expression of P2X7 receptors and c-fos and c-jun mRNA was determined with real-time reverse transcription polymerase chain reaction and Western blotting. P2X7-siRNA, apyrase, P2 receptor antagonists, and p38 MAPK inhibitors were used to evaluate the roles of ATP release, P2X7 receptors, and p38 MAPK signaling in shockwave-induced osteogenic hMSCs differentiation. Shockwave treatment released significant amounts (≈ 7 μM) of ATP from hMSCs. Shockwaves and exogenous ATP induced c-fos and c-jun mRNA transcription, p38 MAPK activation, and hMSC differentiation. Removal of ATP with apyrase, targeting of P2X7 receptors with P2X7-siRNA or selective antagonists, or blockade of p38 MAPK with SB203580 prevented osteogenic differentiation of hMSCs. Our findings indicate that shockwaves release cellular ATP that activates P2X7 receptors and downstream signaling events that caused osteogenic differentiation of hMSCs. We conclude that shockwave therapy promotes bone healing through P2X7 receptor signaling, which contributes to hMSC differentiation.

  11. Targeting P(2)X(7) receptor for the treatment of central post-stroke pain in a rodent model.

    PubMed

    Kuan, Yung-Hui; Shih, Hsi-Chien; Tang, Sung-Chun; Jeng, Jiann-Shing; Shyu, Bai-Chuang

    2015-06-01

    Stroke is a leading cause of death and disability in industrialized countries. Approximately 8-14% of stroke survivors suffer from central post-stroke pain (CPSP) when hemorrhagic stroke occurs in lateral thalamic regions, which severely affects their quality of life. Because the mechanisms of CPSP are not well understood, effective treatments have not been developed. In the present study, we tested the hypothesis that persistent CPSP is caused by P(2)X(7)receptor activation after brain tissue damage and subsequent elevations in inflammatory cytokines. A thalamic hemorrhagic rat model was used, characterized by thermal and mechanical allodynia that develops in the subacute to chronic phases upon CPSP onset. We found a significant increase in P(2)X(7) expression in reactive microglia/macrophages in thalamic peri-lesion tissues at 5 weeks post-hemorrhage. Thalamic P(2)X(7) receptors were directly involved in pain transmission and hypersensitivity. The systemic targeting of P(2)X(7) receptors during the acute stage of hemorrhage rescued abnormal pain behaviors and neuronal activity in the thalamocingulate pathway by reducing reactive microglia/macrophage aggregation and associated inflammatory cytokines. After CPSP onset, the targeting of interleukin-1β reversed abnormal pain sensitivity. The aberrant spontaneous thalamocortical oscillations in rats with CPSP were modulated by blocking P(2)X(7) receptors. Taken together, our results suggest that targeting P(2)X(7) may be bi-effective in the treatment of CPSP, as both a pain blocker and immunosuppressant that inhibits inflammatory damage to brain tissue. P(2)X(7)receptors may serve as a potential target to prevent the occurrence of CPSP and may be beneficial for the recovery of patients from stroke.

  12. N-Alkyl-Substituted Isatins Enhance P2X7 Receptor-Induced Interleukin-1β Release from Murine Macrophages.

    PubMed

    Sluyter, Ronald; Vine, Kara L

    2016-01-01

    Extracellular adenosine 5'-triphosphate (ATP) activates the P2X7 receptor channel to induce the rapid release of the proinflammatory cytokine, interleukin- (IL-) 1β, from macrophages. Microtubule rearrangements are thought to be involved in this process. Some isatin derivatives alter microtubules and display anticancer activities. The current study investigated the effect of isatin and seven structurally diverse isatin derivatives on P2X7-mediated IL-1β release from murine J774 macrophages. ATP-induced IL-1β and lactate dehydrogenase (LDH) release were assessed by specific colorimetric assays. P2X7 activity was determined by flow cytometric measurements of ATP-induced cation dye uptake. Cytotoxicity of isatin derivatives was determined using a tetrazolium-based colorimetric assay. ATP caused rapid IL-1β release in a concentration-dependent manner, and this process was completely impaired by the P2X7 antagonist, AZ10606120. In contrast, 5,7-dibromo-N-(p-methoxybenzyl)isatin (NAI) and 3-{4-[5,7-dibromo-1-(4-methoxybenzyl)-2-oxoindolin-3-ylidenamino]phenyl}propanoic acid (NAI-imine) enhanced P2X7-induced IL-1β release by twofold compared to that of isatin and the parent molecule, 5,7-dibromoisatin. NAI and NAI-imine had minimal effect on P2X7-induced dye uptake and LDH release. In contrast, 24-hour incubation with NAI and NAI-imine (in the absence of exogenous ATP) induced macrophage death in a concentration-dependent manner. In conclusion, this study demonstrates that N-alkyl-substituted isatins enhance P2X7 receptor-induced IL-1β release from murine macrophages. Thus, in addition to direct anticancer effects, these compounds may also impact inflammatory and immune cells within the tumor microenvironment.

  13. Expression level of P2X7 receptor is a determinant of ATP-induced death of mouse cultured neurons.

    PubMed

    Ohishi, A; Keno, Y; Marumiya, A; Sudo, Y; Uda, Y; Matsuda, K; Morita, Y; Furuta, T; Nishida, K; Nagasawa, K

    2016-04-05

    Activation of P2X7 receptor (P2X7R), a purinergic receptor, expressed by neurons is well-known to induce their death, but whether or not their sensitivity to ATP depends on its expression levels remains unclear. Here, we examined the effect of the expression level of P2X7Rs on cell viability using pure neuron cultures, co-cultures with astrocytes derived from SJL- and ddY-strain mice, and mouse P2X7R-expressing HEK293T cell systems. Treatment of pure neuron cultures with 5mM ATP for 2h, followed by 3-h incubation in fresh medium, resulted in death of both types of neurons, and their death was prevented by administration of P2X7R-specific antagonists. In both SJL- and ddY-neurons, ATP-induced neuronal death was inhibited by a mitochondrial permeability transition pore inhibitor cyclosporine A, mitochondrial dysfunction being involved in their death. The ATP-induced neuronal death was greater for SJL-neurons than for ddY-ones, this being correlated with the expression level of P2X7R in them, and the same results were obtained for the HEK293T cell systems. Co-culture of neurons with astrocytes increased the ATP-induced neuronal death compared to the case of pure neuron cultures. Overall, we reveal that neuronal vulnerability to ATP depends on the expression level of P2X7R, and co-existence of astrocytes exacerbates ATP-induced neuronal death.

  14. CLOSURE DEVICE

    DOEpatents

    Linzell, S.M.; Dorcy, D.J.

    1958-08-26

    A quick opening type of stuffing box employing two banks of rotatable shoes, each of which has a caraming action that forces a neoprene sealing surface against a pipe or rod where it passes through a wall is presented. A ring having a handle or wrench attached is placed eccentric to and between the two banks of shoes. Head bolts from the shoes fit into slots in this ring, which are so arranged that when the ring is rotated a quarter turn in one direction the shoes are thrust inwardly to cramp the neopnrene about the pipe, malting a tight seal. Moving the ring in the reverse direction moves the shoes outwardly and frees the pipe which then may be readily removed from the stuffing box. This device has particular application as a closure for the end of a coolant tube of a neutronic reactor.

  15. Optoelectronic device

    DOEpatents

    Bonekamp, Jeffrey E.; Boven, Michelle L.; Gaston, Ryan S.

    2014-09-09

    The invention is an optoelectronic device comprising an active portion which converts light to electricity or converts electricity to light, the active portion having a front side for the transmittal of the light and a back side opposite from the front side, at least two electrical leads to the active portion to convey electricity to or from the active portion, an enclosure surrounding the active portion and through which the at least two electrical leads pass wherein the hermetically sealed enclosure comprises at the front side of the active portion a barrier material which allows for transmittal of light, one or more getter materials disposed so as to not impede the transmission of light to or from the active portion, and a contiguous gap pathway to the getter material which pathway is disposed between the active portion and the barrier material.

  16. PLASMA DEVICE

    DOEpatents

    Baker, W.R.

    1961-08-22

    A device is described for establishing and maintaining a high-energy, rotational plasma for use as a fast discharge capacitor. A disc-shaped, current- conducting plasma is formed in an axinl magnetic field and a crossed electric field, thereby creating rotational kinetic enengy in the plasma. Such energy stored in the rotation of the plasma disc is substantial and is convertible tc electrical energy by generator action in an output line electrically coupled to the plasma volume. Means are then provided for discharging the electrical energy into an external circuit coupled to the output line to produce a very large pulse having an extremely rapid rise time in the waveform thereof. (AE C)

  17. Electrophoresis device

    NASA Technical Reports Server (NTRS)

    Rhodes, P. H.; Snyder, R. S. (Inventor)

    1982-01-01

    A device for separating cellular particles of a sample substance into fractionated streams of different cellular species includes a casing having a distribution chamber, a separation chamber, and a collection chamber. The electrode chambers are separated from the separation chamber interior by means of passages such that flow variations and membrane variations around the slotted portion of the electrode chamber do not enduce flow perturbations into the laminar buffer curtain flowing in the separation chamber. The cellular particles of the sample are separated under the influence of the electrical field and the separation chamber into streams of different cellular species. The streams of separated cells enter a partition array in the collection chamber where they are fractionated and collected.

  18. The Unusual Metal-Insulator Transition in Ca(2-x)Sr(x)RuO(4)

    NASA Astrophysics Data System (ADS)

    Rice, T. Maurice

    2002-03-01

    The isoelectronic compounds Ca_2-xSr_xRuO4 offer a rare opportunity to follow the evolution of the electronic structure from a multiband metal, Sr_2RuO_4, to a Mott insulator, Ca_2RuO_4. The evolution is not at all monotonic but proceeds through a series of intermediate regions with unexpected behavior [1]. Sr_2RuO4 is a good metal with the 4 electrons in the t_2g-subshell of the Ru^4+-ions distributed equally in 3 bands. These in turn separate into a d_xy-band which disperses in both directions in the RuO_2-planes and d_xz/d_yz-bands dispersing only in one direction. The hybridization between these components occurs only through very weak interplanar processes. Substituting Ca for Sr leads to band narrowing through a rotation of the RuO_4-octahedra. A series of electronic structure calculations [2] using the LDA+DMFT method to incorporate strong correlations, predict an unusual state with 3 electrons localizing in the narrower d_xz/d_yz bands while the last electron remains itinerant in the broader d_xy-band. The observation of a strongly enhanced and temperature dependent spin susceptibility in the metallic state at x=0.5 is attributed to the S=1/2 local moments of the localized hole in the d_xz/d_yz-orbitals. The superexchange interaction between the local moments is strongly dependent on the specific orbital occupation and so glassy behavior in the orbital ordering can account for the glassy behavior observed in the susceptibility in the range 0.2 < x < 0.5. The final transition to a Mott insulator at x < 0.2 is driven by a compression of the RuO_4-octahedra and a switch to an electronic configuration with a filled d_xy-orbital and 2 electrons in the d_xz/d_yz orbitals which has a S=1 local moment expected for a Ru^4+-ion. [1] S. Nakatsuji and Y. Maeno, Phys. Rev. Lett. 84, 2666 (2000). [2] V.I. Anisimov, I.A. Nekrasov, D.E. Kondakov, T.M. Rice, and M. Sigrist, cond-mat0107095 and Eur. Phys. Jour. B (in press).

  19. Integrated System Health Management (ISHM) for Test Stand and J-2X Engine: Core Implementation

    NASA Technical Reports Server (NTRS)

    Figueroa, Jorge F.; Schmalzel, John L.; Aguilar, Robert; Shwabacher, Mark; Morris, Jon

    2008-01-01

    ISHM capability enables a system to detect anomalies, determine causes and effects, predict future anomalies, and provides an integrated awareness of the health of the system to users (operators, customers, management, etc.). NASA Stennis Space Center, NASA Ames Research Center, and Pratt & Whitney Rocketdyne have implemented a core ISHM capability that encompasses the A1 Test Stand and the J-2X Engine. The implementation incorporates all aspects of ISHM; from anomaly detection (e.g. leaks) to root-cause-analysis based on failure mode and effects analysis (FMEA), to a user interface for an integrated visualization of the health of the system (Test Stand and Engine). The implementation provides a low functional capability level (FCL) in that it is populated with few algorithms and approaches for anomaly detection, and root-cause trees from a limited FMEA effort. However, it is a demonstration of a credible ISHM capability, and it is inherently designed for continuous and systematic augmentation of the capability. The ISHM capability is grounded on an integrating software environment used to create an ISHM model of the system. The ISHM model follows an object-oriented approach: includes all elements of the system (from schematics) and provides for compartmentalized storage of information associated with each element. For instance, a sensor object contains a transducer electronic data sheet (TEDS) with information that might be used by algorithms and approaches for anomaly detection, diagnostics, etc. Similarly, a component, such as a tank, contains a Component Electronic Data Sheet (CEDS). Each element also includes a Health Electronic Data Sheet (HEDS) that contains health-related information such as anomalies and health state. Some practical aspects of the implementation include: (1) near real-time data flow from the test stand data acquisition system through the ISHM model, for near real-time detection of anomalies and diagnostics, (2) insertion of the J-2X

  20. Tanshinone II A sulfonate, but not tanshinone II A, acts as potent negative allosteric modulator of the human purinergic receptor P2X7.

    PubMed

    Kaiser, M; Sobottka, H; Fischer, W; Schaefer, M; Nörenberg, W

    2014-09-01

    Tanshinone II A sulfonate (TIIAS) was identified as a potent, selective blocker of purinergic receptor P2X7 in a compound library screen. In this study, a detailed characterization of the pharmacologic effects of TIIAS on P2X7 is provided. Because TIIAS is a derivative of tanshinone II A (TIIA) and both compounds have been used interchangeably, TIIA was included in some assays. Fluorometric and electrophysiologic assays were used to characterize effects of TIIAS and TIIA on recombinantly expressed human, rat, and mouse P2X7. Results were confirmed in human monocyte-derived macrophages expressing native P2X7. In all experiments, involvement of P2X7 was verified using established P2X7 antagonists. TIIAS, but not TIIA, reduces Ca(2+) influx via human P2X7 (hP2X7) with an IC50 of 4.3 µM. TIIAS was less potent at mouse P2X7 and poorly inhibited rat P2X7. Monitoring of YO-PRO-1 uptake confirmed these findings, indicating that formation of the hP2X7 pore is also suppressed by TIIAS. Electrophysiologic experiments revealed a noncompetitive mode of action. TIIAS time-dependently inhibits hP2X7 gating, possibly by binding to the intracellular domain of the receptor. Inhibition of native P2X7 in macrophages by TIIAS was confirmed by monitoring Ca(2+) influx, YO-PRO-1 uptake, and release of the proinflammatory cytokine interleukin-1β. Fluorometric experiments involving recombinantly expressed rat P2X2 and human P2X4 were conducted and verified the compound's selectivity. Our data suggest that hP2X7 is a molecular target of TIIAS, but not of TIIA, a compound with different pharmacologic properties.

  1. Engineering amorphous-crystalline interfaces in TiO2-x/TiO2-y-based bilayer structures for enhanced resistive switching and synaptic properties

    NASA Astrophysics Data System (ADS)

    Bousoulas, P.; Asenov, P.; Karageorgiou, I.; Sakellaropoulos, D.; Stathopoulos, S.; Tsoukalas, D.

    2016-10-01

    The operating principle of resistive random access memories (RRAMs) relies on the distribution of ionic species and their influence on the electron transport. Taking into account that formation and annihilation of conducting filaments (CFs) is the driving mechanism for the switching effect, it is very important to control the regions where these filaments will evolve. Thus, homolayers of titanium oxide with different oxygen contents were fabricated in order to tune the local electrical and thermal properties of the CFs and narrow down the potential percolation paths. We show that the oxygen content in the top layer of the TiO2-x/TiO2-y bilayer memristors can directly influence the morphology of the layers which affect the diffusion barrier and consequently the diffusivity and drift velocity of oxygen vacancies, yielding in important enhancement of switching characteristics, in terms of spatial uniformity (σ/μ < 0.2), enlarged switching ratio (˜104), and synaptic learning. In order to address the experimental data, a physical model was applied, divulging the crucial role of temperature, electric potential and oxygen vacancy density on the switching effect and offering physical insights to the SET/RESET transitions and the analog switching. The forming free nature of all the devices in conjunction with the self-rectifying behavior, should also be regarded as important assets towards RRAM device optimization.

  2. Neuronal Release of Cytokine IL-3 Triggered by Mechanosensitive Autostimulation of the P2X7 Receptor Is Neuroprotective

    PubMed Central

    Lim, Jason C.; Lu, Wennan; Beckel, Jonathan M.; Mitchell, Claire H.

    2016-01-01

    Mechanical strain due to increased pressure or swelling activates inflammatory responses in many neural systems. As cytokines and chemokine messengers lead to both pro-inflammatory and neuroprotective actions, understanding the signaling patterns triggered by mechanical stress may help improve overall outcomes. While cytokine signaling in neural systems is often associated with glial cells like astrocytes and microglia, the contribution of neurons themselves to the cytokine response is underappreciated and has bearing on any balanced response. Mechanical stretch of isolated neurons was previously shown to trigger ATP release through pannexin hemichannels and autostimulation of P2X7 receptors (P2X7Rs) on the neural membrane. Given that P2X7Rs are linked to cytokine activation in other cells, this study investigates the link between neuronal stretch and cytokine release through a P2X7-dependent pathway. Cytokine assays showed application of a 4% strain to isolated rat retinal ganglion cells (RGCs) released multiple cytokines. The P2X7R agonist BzATP also released multiple cytokines; Interleukin 3 (IL-3), TNF-α, CXCL9, VEGF, L-selectin, IL-4, GM-CSF, IL-10, IL-1Rα, MIP and CCL20 were released by both stimuli, with the release of IL-3 greatest with either stimuli. Stretch-dependent IL-3 release was confirmed with ELISA and blocked by P2X7R antagonists A438079 and Brilliant Blue G (BBG), implicating autostimulation of the P2X7R in stretch-dependent IL-3 release. Neuronal IL-3 release triggered by BzATP required extracellular calcium. The IL-3Rα receptor was expressed on RGCs but not astrocytes, and both IL-3Rα and IL-3 itself were predominantly expressed in the retinal ganglion cell layer of adult retinal sections, implying autostimulation of receptors by released IL-3. While the number of surviving ganglion cells decreased with time in culture, the addition of IL-3 protected against this loss of neurons. Expression of mRNA for IL-3 and IL-3Rα increased in rat

  3. Properties of native P2X receptors in large multipolar neurons dissociated from rat hypothalamic arcuate nucleus.

    PubMed

    Wakamori, Minoru; Sorimachi, Masaru

    2004-04-16

    ATP, the ligand of P2X receptors, is a candidate of neurotransmitter or co-transmitter in the peripheral and the central nervous systems. Anatomical studies have revealed the wide distribution of P2X receptors in the brain. So far, P2X-mediated small synaptic responses have been recorded in some brain regions. To determine the physiological significance of postsynaptic ATP receptors in the brain, we have investigated the P2X responses in rat dissociated hypothalamic arcuate neurons by using the patch-clamp technique. ATP evoked inward currents in a concentration-dependent manner (EC(50)=42 microM) at a holding potential of -70 mV. The current-voltage relationship showed a marked inward rectification starting around -10 mV. Although neither 300 microM alphabeta-methylene-ATP nor 300 microM betagamma-methylene-ATP induced any currents, 100 microM ATPgammaS and 100 microM 2-methylthio-ATP evoked inward currents of which amplitude was about 60% of the control currents evoked by 100 microM ATP. PPADS, one of P2 receptor antagonists, inhibited the ATP-evoked currents in a time- and a concentration-dependent manners (IC(50)=19 microM at 2 min). Permeant Ca(2+) inhibited the ATP-evoked currents in the range of millimolars (IC(50)=7 mM); however, Cd(2+) (1-300 microM), a broad cation channel blocker, facilitated the currents with slow off-response. Zn(2+) in the range of 1-100 microM facilitated the currents whereas Zn(2+) at the concentrations over 100 microM inhibited the currents. These observations suggest that functional P2X receptors are expressed in the hypothalamic arcuate nucleus. The most likely subunit combinations of the P2X receptors are P2X(2)-homomultimer and P2X(2)/P2X(6)-heteromultimer.

  4. Effects of protein deprivation and re-feeding on P2X2 receptors in enteric neurons

    PubMed Central

    Misawa, Rúbia; Girotti, Priscila Azevedo; Mizuno, Márcia Sanae; Liberti, Edson Aparecido; Furness, John Barton; Castelucci, Patricia

    2010-01-01

    AIM: To investigate the effects of malnutrition and re-feeding on the P2X2 receptor, nitric oxide synthase (NOS), calretinin, calbindin and choline acetyltransferase (ChAT) in neurons of the rat ileum. METHODS: We analyzed the co-localization, numbers and sizes of P2X2-expressing neurons in relation to NOS-immunoreactive (IR), calbindin-IR, ChAT-IR, and calretinin-IR neurons of the myenteric and submucosal plexus. The experimental groups consisted of: (1) rats maintained on normal feed throughout pregnancy until 42 d post-parturition (N); (2) rats deprived of protein throughout pregnancy and 42 d post-parturition (D); and (3) rats undernourished for 21 d post-parturition and then given a protein diet from days 22 to 42 (DR). The myenteric and submucosal plexuses were evaluated by double labeling by immunohistochemical methods for P2X2 receptor, NOS, ChAT, calbindin and calretinin. RESULTS: We found similar P2X2 receptor immunoreactivity in the cytoplasm and surface membranes of myenteric and submucosal neurons from the N, D and DR groups. Double labeling of the myenteric plexus demonstrated that approximately 100% of NOS-IR, calbindin-IR, calretinin-IR and ChAT-IR neurons in all groups also expressed the P2X2 receptor. In the submucosal plexus, the calretinin-IR, ChAT-IR and calbindin-IR neurons were nearly all immunoreactive for the P2X2 receptor. In the myenteric plexus, there was a 19% increase in numbers per cm2 for P2X2 receptor-IR neurons, 64% for NOS-IR, 84% for calretinin-IR and 26% for ChAT-IR neurons in the D group. The spatial density of calbindin-IR neurons, however, did not differ among the three groups. The submucosal neuronal density increased for calbindin-IR, calretinin-IR and ChAT-IR neurons. The average size of neurons in the myenteric plexus neurons in the D group was less than that in the controls and, in the re-fed rats; there was a 34% reduction in size only for the calretinin-IR neurons. CONCLUSION: This work demonstrates that expression of

  5. Activation of P2X7 receptors in the midbrain periaqueductal gray of rats facilitates morphine tolerance.

    PubMed

    Xiao, Zhi; Li, You-Yan; Sun, Meng-Jie

    2015-08-01

    Opiates such as morphine exhibit analgesic effect in various pain models, but repeated and chronic morphine administration may develop resistance to antinociception. The purinergic signaling system is involved in the mechanisms of pain modulation and morphine tolerance. This study aimed to determine whether the P2X7 receptor in the ventrolateral midbrain periaqueductal gray (vlPAG) is involved in morphine tolerance. Development of tolerance to the antinociceptive effect of morphine was induced in normal adult male Sprague-Dawley (SD) rats through subcutaneous injection of morphine (10mg/kg). The analgesic effect of morphine (5mg/kg, i.p.) was assessed by measuring mechanical withdrawal thresholds (MWTs) in rats with an electronic von Frey anesthesiometer. The expression levels and distribution of the P2X7 receptor in the vlPAG was evaluated through Western blot analysis and immunohistochemistry. The acute effects of intra-vlPAG injection of the selective P2X7 receptor agonist Bz-ATP, the selective P2X7 receptor antagonist A-740003, or antisense oligodeoxynucleotide (AS ODN) targeting the P2X7 receptor on morphine-treated rats were also observed. Results demonstrated that repeated morphine administration decreased the mechanical pain thresholds. By contrast, the expression of the P2X7 receptor protein was up-regulated in the vlPAG in morphine tolerant rats. The percent changes in MWT were markedly but only transiently attenuated by intra-vlPAG injection of Bz-ATP (9nmol/0.3μL) but elevated by A-740003 at doses of 10 and 100nmol/0.3μL. AS ODN (15nmol/0.3μL) against the P2X7 receptor reduced the development of chronic morphine tolerance in rats. These results suggest that the development of antinociceptive tolerance to morphine is partially mediated by activating the vlPAG P2X7 receptors. The present data also suggest that the P2X7 receptors may be a therapeutic target for improving the analgesic effect of morphine in treatments of pain when morphine tolerance

  6. P2X7 Receptor Regulates Internalization of Antimicrobial Peptide LL-37 by Human Macrophages That Promotes Intracellular Pathogen Clearance.

    PubMed

    Tang, Xiao; Basavarajappa, Devaraj; Haeggström, Jesper Z; Wan, Min

    2015-08-01

    Bioactive peptide LL-37/hCAP18, the only human member of the cathelicidin family, plays important roles in killing various pathogens, as well as in immune modulation. We demonstrate that LL-37 is internalized by human macrophages in a time-, dose-, temperature-, and peptide sequence-dependent endocytotic process. Both clathrin- and caveolae/lipid raft-mediated endocytosis pathways are involved in LL-37 internalization. We find that the P2X7 receptor (P2X7R) plays an important role in LL-37 internalization by human macrophages because significantly less internalized LL-37 was detected in macrophages pretreated with P2X7R antagonists or, more specifically, in differentiated THP-1 cells in which the P2X7R gene had been silenced. Furthermore, this P2X7R-mediated LL-37 internalization is primarily connected to the clathrin-mediated endocytosis pathway. In addition, our results demonstrate that internalized LL-37 traffics to endosomes and lysosomes and contributes to intracellular clearance of bacteria by human macrophages, coinciding with increased reactive oxygen species and lysosome formation. Finally, we show that human macrophages have the potential to import LL-37 released from activated human neutrophils. In conclusion, our study unveils a novel mechanism by which human macrophages internalize antimicrobial peptides to improve their intracellular pathogen clearance.

  7. The effect of sinomenine in diabetic neuropathic pain mediated by the P2X3 receptor in dorsal root ganglia.

    PubMed

    Rao, Shenqiang; Liu, Shuangmei; Zou, Lifang; Jia, Tianyu; Zhao, Shanhong; Wu, Bing; Yi, Zhihua; Wang, Shouyu; Xue, Yun; Gao, Yun; Xu, Changshui; Li, Guilin; Xu, Hong; Zhang, Chunping; Liang, Shangdong

    2017-01-04

    Type 2 diabetes mellitus (T2DM) accounts for more than 90% of all cases of diabetes mellitus (DM). Diabetic neuropathic pain (DNP) is a common complication of T2DM. Sinomenine is a natural bioactive component extracted from the Sinomenium acutum and has anti-inflammatory effects. The aim of our study was to investigate the effects of sinomenine on DNP mediated by the P2X3 receptor in dorsal root ganglia (DRG). The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) in T2DM rats were lower than those of control rats. MWT and TWL in T2DM rats treated with sinomenine were higher compared with those in T2DM rats. The expression levels of the P2X3 protein and mRNA in T2DM rat DRG were higher compared with those of the control, while those in T2DM rats treated with sinomenine were significantly lower compared with those of the T2DM rats. Sinomenine significantly inhibited P2X3 agonist ATP-activated currents in HEK293 cells transfected with the P2X3 receptor. Sinomenine decreased the phosphorylation and activation of P38MAPK in T2DM DRG. Therefore, sinomenine treatment may suppress the up-regulated expression and activation of the P2X3 receptor and relieve the hyperalgesia potentiated by the activation of P38MAPK in T2DM rats.

  8. Anoctamin 6 mediates effects essential for innate immunity downstream of P2X7 receptors in macrophages

    NASA Astrophysics Data System (ADS)

    Ousingsawat, Jiraporn; Wanitchakool, Podchanart; Kmit, Arthur; Romao, Ana M.; Jantarajit, Walailak; Schreiber, Rainer; Kunzelmann, Karl

    2015-02-01

    Purinergic P2X7 receptors (P2X7R) are fundamental to innate immune response. In macrophages, transient stimulation of P2X7R activates several transport mechanisms and induces the scrambling of phospholipids with subsequent membrane blebbing and apoptosis. These processes support phagocytosis and subsequent killing of phagocytosed bacteria. Here we demonstrate that the stimulation of P2X7 receptors activates anoctamin 6 (ANO6, TMEM16F), a protein that functions as Ca2+ dependent phospholipid scramblase and Ca2+-activated Cl- channel. Inhibition or knockdown of ANO6 attenuates ATP-induced cell shrinkage, cell migration and phospholipid scrambling. In mouse macrophages, Ano6 produces large ion currents by stimulation of P2X7 receptors and contributes to ATP-induced membrane blebbing and apoptosis, which is largely reduced in macrophages from Ano6-/- mice. ANO6 supports bacterial phagocytosis and killing by mouse and human THP-1 macrophages. Our data demonstrate that anoctamin 6 is an essential component of the immune defense by macrophages.

  9. Pharmacological evidence for the stimulation of NADPH oxidase by P2X7 receptors in mouse submandibular glands

    PubMed Central

    Seil, Michèle; Fontanils, Unai; Etxebarria, Irantzu Gorrono; Pochet, Stéphanie; Garcia-Marcos, Mikel; Marino, Aida

    2008-01-01

    ATP in the 100 μM-1 mM concentration range provoked a calcium-independent increase of the oxidation of dichlorodihydrofluorescein (DCFH) to dichlorofluorescein (DCF) by mouse submandibular cells. 3′-O-(4-benzoyl)benzoyl adenosine 5′-triphosphate (BzATP), a P2X7 agonist, but not a muscarinic or an adrenergic agonist, reproduced the effect of ATP. The inhibition of phospholipase C by U73122 or the potentiation of P2X4 receptor activation with ivermectin did not modify the response to ATP. ATP did not increase the oxidation of DCFH in cells isolated from submandibular glands of P2X7 knockout mice or in cells pretreated with a P2X7 antagonist. The inhibition of protein kinase C or of mitogen-activated protein kinase (MAP kinase) or of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase blocked the oxidation of DCFH without affecting the increase of the intracellular concentration of calcium or the uptake of ethidium bromide in response to extracellular ATP. From these results it is concluded that the activation of the P2X7 receptors from submandibular glands triggers an intracellular signalling cascade involving protein kinase C and MAP kinase leading to the stimulation of NADPH oxidase and the subsequent generation of reactive oxygen species. PMID:18581262

  10. Extracellular ATP mediates necrotic cell swelling in SN4741 dopaminergic neurons through P2X7 receptors.

    PubMed

    Jun, Dong-Jae; Kim, Jaeyoon; Jung, Sang-Yong; Song, Ran; Noh, Ji-Hyun; Park, Yong-Soo; Ryu, Sung-Ho; Kim, Joung-Hun; Kong, Young-Yun; Chung, Jun-Mo; Kim, Kyong-Tai

    2007-12-28

    Extracellular ATP has recently been identified as an important regulator of cell death in response to pathological insults. When SN4741 cells, which are dopaminergic neurons derived from the substantia nigra of transgenic mouse embryos, are exposed to ATP, cell death occurs. This cell death is associated with prominent cell swelling, loss of ER integrity, the formation of many large cytoplasmic vacuoles, and subsequent cytolysis and DNA release. In addition, the cleavage of caspase-3, a hallmark of apoptosis, is induced by ATP treatment. However, caspase inhibitors do not overcome ATP-induced cell death, indicating that both necrosis and apoptosis are associated with ATP-induced cell death and suggesting that a necrotic event might override the apoptotic process. In this study we also found that P2X(7) receptors (P2X(7)Rs) are abundantly expressed in SN4741 cells, and both ATP-induced swelling and cell death are reversed by pretreatment with the P2X(7)Rs antagonist, KN62, or by knock-down of P2X(7)Rs with small interfering RNAs. Therefore, extracellular ATP release from injured tissues may act as an accelerating factor in necrotic SN4741 dopaminergic cell death via P2X(7)Rs.

  11. Activation of P2X7 promotes cerebral edema and neurological injury after traumatic brain injury in mice.

    PubMed

    Kimbler, Donald E; Shields, Jessica; Yanasak, Nathan; Vender, John R; Dhandapani, Krishnan M

    2012-01-01

    Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Cerebral edema, the abnormal accumulation of fluid within the brain parenchyma, contributes to elevated intracranial pressure (ICP) and is a common life-threatening neurological complication following TBI. Unfortunately, neurosurgical approaches to alleviate increased ICP remain controversial and medical therapies are lacking due in part to the absence of viable drug targets. In the present study, genetic inhibition (P2X7-/- mice) of the purinergic P2x7 receptor attenuated the expression of the pro-inflammatory cytokine, interleukin-1β (IL-1β) and reduced cerebral edema following controlled cortical impact, as compared to wild-type mice. Similarly, brilliant blue G (BBG), a clinically non-toxic P2X7 inhibitor, inhibited IL-1β expression, limited edemic development, and improved neurobehavioral outcomes after TBI. The beneficial effects of BBG followed either prophylactic administration via the drinking water for one week prior to injury or via an intravenous bolus administration up to four hours after TBI, suggesting a clinically-implementable therapeutic window. Notably, P2X7 localized within astrocytic end feet and administration of BBG decreased the expression of glial fibrillary acidic protein (GFAP), a reactive astrocyte marker, and attenuated the expression of aquaporin-4 (AQP4), an astrocytic water channel that promotes cellular edema. Together, these data implicate P2X7 as a novel therapeutic target to prevent secondary neurological injury after TBI, a finding that warrants further investigation.

  12. First-principles calculations of Mg2X (X = Si, Ge, Sn) semiconductors with the calcium fluorite structure

    NASA Astrophysics Data System (ADS)

    Sandong, Guo

    2015-05-01

    The electronic structures of Mg2X (X = Si, Ge, Sn) have been calculated by using generalized gradient approximation, various screened hybrid functionals, as well as Tran and Blaha's modified Becke and Johnson exchange potential. It was found that the Tran and Blaha's modified Becke and Johnson exchange potential provides a more realistic description of the electronic structures and the optical properties of Mg2X (X = Si, Ge, Sn) than else exchange-correlation potential, and the theoretical gaps and dielectric functions of Mg2X (X = Si, Ge, Sn) are quite compatible with the experimental data. The elastic properties of Mg2X (X = Si, Ge, Sn) have also been studied in detail with the generalized gradient approximation, including bulk modulus, shear modulus, Young's modulus, Poisson's ratio, sound velocities, and Debye temperature. The phonon dispersions of Mg2X (X = Si, Ge, Sn) have been calculated within the generalized gradient approximation, suggesting no structural instability, and the measurable phonon heat capacity as a function of the temperature has been also calculated. Project supported by the Fundamental Research Funds for the Central Universities (No. 2013QNA32) and the National Natural Science Foundation of China (No. 11404391).

  13. Entanglement and dissipation in a 2x2 quantum-dot cell

    NASA Astrophysics Data System (ADS)

    Debora Contreras, Lesbia; Rojas, Fernando

    2005-03-01

    Quantum dot arrays or quantum-dot cellular automata (QCA) have been proposed as elements capable to encode, process and transmit logical information based on quantum effects in terms of charge distributions in specific geometries. and the basis for the charge qubits. Quantum Entanglement is a resource to encode information in a completely new way making possible quantum teleportation, quantum error correction, quantum dense coding. In this work, we explore the dynamical formation of entangled states including dissipative effects, of two parallel double dots (four dots, 2x2 cell), with one extra electron each, coupled by the Coulomb interaction and controlled by a time dependent potential difference applied to one of the double dots, causing the electron to switch. We include dissipative effects via electron-phonon interaction in the Markovian approximation for the reduced density matrix. Dynamical properties of the cell such as charge polarization, measure the entanglement (Wootters concurrence) and the probabilities for each Bell state, are discussed as a function of relevant parameters (tunneling, potential difference, temperature). We find that it is possible to obtain entangled states in the cell based on the electronic charge distribution and produce a specific Bell state from an initially non entangled state through the control of the time dependent potential. The work is supported by DGAPA project IN114403 and CONACyT project 43673-F

  14. Elucidating the foundations of statistical inference with 2 x 2 tables.

    PubMed

    Choi, Leena; Blume, Jeffrey D; Dupont, William D

    2015-01-01

    To many, the foundations of statistical inference are cryptic and irrelevant to routine statistical practice. The analysis of 2 x 2 contingency tables, omnipresent in the scientific literature, is a case in point. Fisher's exact test is routinely used even though it has been fraught with controversy for over 70 years. The problem, not widely acknowledged, is that several different p-values can be associated with a single table, making scientific inference inconsistent. The root cause of this controversy lies in the table's origins and the manner in which nuisance parameters are eliminated. However, fundamental statistical principles (e.g., sufficiency, ancillarity, conditionality, and likelihood) can shed light on the controversy and guide our approach in using this test. In this paper, we use these fundamental principles to show how much information is lost when the tables origins are ignored and when various approaches are used to eliminate unknown nuisance parameters. We present novel likelihood contours to aid in the visualization of information loss and show that the information loss is often virtually non-existent. We find that problems arising from the discreteness of the sample space are exacerbated by p-value-based inference. Accordingly, methods that are less sensitive to this discreteness - likelihood ratios, posterior probabilities and mid-p-values - lead to more consistent inferences.

  15. Frustrated spin correlations in diluted spin ice Ho2-xLaxTi2O7

    SciTech Connect

    Ehlers, Georg; Ehlers, G.; Mamontov, E.; Zamponi, M.; Faraone, A.; Qiu, Y.; Cornelius, A.L.; Booth, C.H.; Kam, K.C.; Le Toquin, R.; Cheetham, A.K.; Gardner, J.S.

    2008-04-30

    We have studied the evolution of the structural properties as well as the static and dynamic spin correlations of spin ice Ho2Ti2O7, where Ho was partially replaced by non-magnetic La. The crystal structure of diluted samples Ho2-xLaxTi2O7 was characterized by x-ray and neutron diffraction and by Ho L-III-edge and Ti K-edge extended x-ray absorption fine structure (EXAFS) measurements. It is found that the pyrochlore structure remains intact until about x = 0.3, but a systematic increase in local disorder with increasing La concentration is observed in the EXAFS data, especially from the Ti K edge.Quasi-elastic neutron scattering and ac susceptibility measurements show that, in x<= 0.4 samples at temperatures above macroscopic freezing, the spin -spin correlations are short ranged and dynamic in nature. The main difference with pure spin ice in the dynamics is the appearance of a second, faster, relaxation process.

  16. Thermodynamic and electrical transport investigation of URu2Si2-x P x

    NASA Astrophysics Data System (ADS)

    Gallagher, A.; Chen, K.-W.; Cary, S. K.; Kametani, F.; Graf, D.; Albrecht-Schmitt, T. E.; Shekhter, A.; Baumbach, R. E.

    2017-01-01

    Magnetic susceptibility, electrical resistivity, and heat capacity results are reported for the chemical substitution series URu2Si2-x P x for 0. This study expands in detail on work recently reported in Gallagher et al (2016 Nat. Commun. 10712), which focused on the small x region of this substitution series. Measurements presented here reveal persistent hybridization between the f- and conduction electrons and strong variation of the low temperature behavior with increasing x. Hidden order and superconductivity are rapidly destroyed for x≲ 0.03 and are replaced for 0.03≲ x≲ 0.26 by a region with Kondo coherence but no ordered state. Antiferromagnetism abruptly appears for x≳ 0.27 . This phase diagram differs significantly from those produced by most other tuning strategies in URu2Si2, including applied pressure, high magnetic fields, and isoelectronic chemical substitution (i.e. Ru  →  Fe and Os), where hidden order and magnetism share a common phase boundary. Besides revealing an intriguing evolution of the low temperature states, this series provides a setting in which to investigate the influence of electronic tuning, where probes that are sensitive to the Fermi surface and the symmetry of the ordered states will be useful to unravel the anomalous behavior of URu2Si2.

  17. Effects of a 2X gravity environment on the ultrastructure of the gerbil parathyroid gland

    NASA Technical Reports Server (NTRS)

    Sannes, P. L.; Hayes, T. G.

    1975-01-01

    A number of studies concerning the effects of hypergravity on bone have shown increases in bone mass or bone dimensions. Correlative studies, which could provide clues to the mechanism for such a response, have been lacking. The purpose of the present study was to evaluate the ultrastructure of parathyroid glands of Mongolian gerbils exposed to a continuous 2 X gravity force for 60 d. It was found that the experimental animals had parathyroid glands which had a greater percentage of chief cells in the active stage of their secretory cycle when compared with control animals. This result was interpreted to indicate an increase in parathyroid gland secretory activity and, hence, an increase in parathyroid hormone release. It was suggested that increased parathyroid secretory activity was necessary to maintain serum calcium levels of hypergravity animals within normal limits. Cellular forms resembling water clear cells and highly compact, degenerating cells were described in experimental animals but not in controls. Areas suggestive of cellular dissolution and disorganization were also reported in experimental parathyroids.

  18. Helium release and microstructural changes in Er(D,T)2-x3Hex films).

    SciTech Connect

    Gelles, D. S.; Browning, James Frederick; Snow, Clark Sheldon; Banks, James Clifford; Mangan, Michael A.; Rodriguez, Mark Andrew; Brewer, Luke N.; Kotula, Paul Gabriel

    2007-12-01

    Er(D,T){sub 2-x} {sup 3}He{sub x}, erbium di-tritide, films of thicknesses 500 nm, 400 nm, 300 nm, 200 nm, and 100 nm were grown and analyzed by Transmission Electron Microscopy, X-Ray Diffraction, and Ion Beam Analysis to determine variations in film microstructure as a function of film thickness and age, due to the time-dependent build-up of {sup 3}He in the film from the radioactive decay of tritium. Several interesting features were observed: One, the amount of helium released as a function of film thickness is relatively constant. This suggests that the helium is being released only from the near surface region and that the helium is not diffusing to the surface from the bulk of the film. Two, lenticular helium bubbles are observed as a result of the radioactive decay of tritium into {sup 3}He. These bubbles grow along the [111] crystallographic direction. Three, a helium bubble free zone, or 'denuded zone' is observed near the surface. The size of this region is independent of film thickness. Four, an analysis of secondary diffraction spots in the Transmission Electron Microscopy study indicate that small erbium oxide precipitates, 5-10 nm in size, exist throughout the film. Further, all of the films had large erbium oxide inclusions, in many cases these inclusions span the depth of the film.

  19. Polytypism, polymorphism, and superconductivity in TaSe(2-x)Te(x).

    PubMed

    Luo, Huixia; Xie, Weiwei; Tao, Jing; Inoue, Hiroyuki; Gyenis, András; Krizan, Jason W; Yazdani, Ali; Zhu, Yimei; Cava, Robert Joseph

    2015-03-17

    Polymorphism in materials often leads to significantly different physical properties--the rutile and anatase polymorphs of TiO2 are a prime example. Polytypism is a special type of polymorphism, occurring in layered materials when the geometry of a repeating structural layer is maintained but the layer-stacking sequence of the overall crystal structure can be varied; SiC is an example of a material with many polytypes. Although polymorphs can have radically different physical properties, it is much rarer for polytypism to impact physical properties in a dramatic fashion. Here we study the effects of polytypism and polymorphism on the superconductivity of TaSe2, one of the archetypal members of the large family of layered dichalcogenides. We show that it is possible to access two stable polytypes and two stable polymorphs in the TaSe(2-x)Te(x) solid solution and find that the 3R polytype shows a superconducting transition temperature that is between 6 and 17 times higher than that of the much more commonly found 2H polytype. The reason for this dramatic change is not apparent, but we propose that it arises either from a remarkable dependence of Tc on subtle differences in the characteristics of the single layers present or from a surprising effect of the layer-stacking sequence on electronic properties that are typically expected to be dominated by the properties of a single layer in materials of this kind.

  20. Quantum criticality in electron-doped BaFe2-xNixAs2.

    PubMed

    Zhou, R; Li, Z; Yang, J; Sun, D L; Lin, C T; Zheng, Guo-qing

    2013-01-01

    A quantum critical point is a point in a system's phase diagram at which an order is completely suppressed at absolute zero temperature (T). The presence of a quantum critical point manifests itself in the finite-T physical properties, and often gives rise to new states of matter. Superconductivity in the cuprates and in heavy fermion materials is believed by many to be mediated by fluctuations associated with a quantum critical point. In the recently discovered iron-pnictide superconductors, we report transport and NMR measurements on BaFe(2-x)Ni(x)As₂ (0≤x≤0.17). We find two critical points at x(c1)=0.10 and x(c2)=0.14. The electrical resistivity follows ρ=ρ₀+AT(n), with n=1 around x(c1) and another minimal n=1.1 at x(c2). By NMR measurements, we identity x(c1) to be a magnetic quantum critical point and suggest that x(c2) is a new type of quantum critical point associated with a nematic structural phase transition. Our results suggest that the superconductivity in carrier-doped pnictides is closely linked to the quantum criticality.

  1. 2 X 64 GaAs readout for IR FPA application

    NASA Astrophysics Data System (ADS)

    Kozlowski, L. J.; Kezer, R. E.

    1992-07-01

    A high-speed 2 x 64 GaAs readout with direct injection input has been demonstrated. The readout was fabricated in E/D MESFET technology and is intended for hybridization to photovoltaic detector arrays, specifically PV HgCdTe, for use at long wavelength infrared (LWIR) backgrounds (greater than 5 x 10 exp 15 photons/sq cm). System-limited data rate of 50 MHz was achieved at reasonable power dissipation of not greater than 125 mW. Enhancement-mode MESFETs in both implanted and heterostructure E/D MESFET structures were observed to have low 1/f noise and high subthreshold ideality. The noise spectral density of superlattice-buffered heterostructure E-MESFETs operating at drain current of 500 nA (nominal tactical LWIR detector current) was typically about 2 micro-V/Hz exp 1/2 at 1 Hz, which is comparable to silicon NMOS. This is lower than needed for background limited IR photodetector focal plane array sensitivity.

  2. Doping Dependence of Spin and Phonon Hybridization in La2 - xBAxCuO4

    NASA Astrophysics Data System (ADS)

    Wagman, Jerod; Carlo, J. P.; van Gastel, G.; Stone, M. B.; Niedziela, J. L.; Granroth, G. E.; Koleshnikov, A. I.; Debeer-Schmitt, L.; Savici, A. T.; Yamani, Z.; Tun, Z.; Zhao, Y.; Kallin, A. B.; Mazurek, E.; Dabkowska, H. A.; Gaulin, B. D.

    2014-03-01

    'Hour-glass' shaped dispersions of antiferromagnetic (AF) spin fluctuations are a robust feature common to many high temperature superconductors. In La-214 cuprates, these phenomena are well known to display a strong dependence on the concentration of holes that are introduced into the copper oxide planes by doping. Here, we present a series of neutron scattering measurements on single crystals of La2 - x Bax CuO4 (LBCO), with 0 <= x <= 0 . 095 . This is a doping range that spans the phase diagram from insulating three dimensional commensurate AF to superconducting two dimensional incommensurate AF. Our measurements comprehensively map out the evolution of the spin excitations below ~ 40 meV. In particular, we focus on the rich structures that arise at the many crossings of the highly dispersive spin excitations with the many phonon eigenvectors in this system. The nature of these structures are suggestive of spin-phonon hybridized modes, which seem to pervade the phase diagram of LBCO. NSERC, Sci. User Facilities Div., Off. of Basic Energy Sci., US DOE.

  3. Structural and electronic properties of XSi{sub 2} (X = Cr, Mo, and W)

    SciTech Connect

    Shugani, Mani; Aynyas, Mahendra; Sanyal, S. P.

    2015-07-15

    The structural and electronic properties of metal silicides XSi{sub 2} (X = Cr, Mo, and W), which crystallize in tetragonal structure, are investigated systematically using the first-principle density functional theory. The total energies are computed as a function of volume and fitted to the Birch equation of state. The ground-state properties such as equilibrium lattice constants a{sub 0} and c{sub 0}, bulk modulus B, its pressure derivative B, B′, and the density of states at the Fermi level, N(E{sub F}), are calculated and compared with other experimental and theoretical results, showing good agreement. The calculated band structure indicates that XSi{sub 2} compounds are semimetallic in nature. From the present study, we predict the structural and electronic properties of CrSi{sub 2} in the tetragonal phase and indicate that CrSi{sub 2} is energetically more stable than MoSi{sub 2} and WSi{sub 2}. Analyzing the bonding properties of the three metal silicides, we observe that WSi{sub 2} has a strong covalent bonding due to W 5d electrons.

  4. Improving inspectability of sub-2x-nm node masks with complex SRAF

    NASA Astrophysics Data System (ADS)

    Kang, In Yong; Yoon, Gisung; Lee, Jonghee; Chung, Donghoon Paul; Kim, Byung-Gook; Jeon, Chan-Uk; Inderhees, Gregg; Hutchinson, Trent; Cho, Wonil; Hur, Jiuk

    2013-10-01

    As Moore's Law continues its relentless march toward ever smaller geometries on wafer, lithographers who had been relying on the implementation of a solution using EUV lithography are faced with increasing challenges to meet requirements for printing sub-2x nm half-pitch (HP). The available choices rely on 193 nm DUV immersion lithography, but with decreasing k1 values and thus shrinking process windows. To overcome these limitations, two techniques such as inverse lithography technology (ILT) and source mask optimization (SMO) were introduced by computational OPC scheme. From a mask inspection viewpoint, the impact of both ILT and SMO is similar - both result in photomasks that have a large quantity of sub-resolution assist features (SRAFs). These SRAFs are challenging for mask-makers to pattern with high fidelity and accuracy across a full-field mask, and thus mask inspection is challenged to maintain a high sensitivity level on primary mask features while not suffering from a high nuisance detection rate on the SRAF features. To solve this particular issue, new inspection approach was developed by using computational image calibration based wafer scanner simulation. This paper will be described the new capabilities, which analyzes the aerial image to differentiate between printing and non-printing features, and applying the appropriate sensitivity threshold. All analysis will be shown comparing results with and without the new capabilities, with an emphasis on inspectability improvements and nuisance defect reduction to improve mask cycle time.

  5. Glutathione induces GABA release through P2X7R activation on Müller glia.

    PubMed

    Freitas, Hércules Rezende; Reis, Ricardo A de Melo

    2017-01-01

    The retinal tissue of warm-blooded vertebrates performs surprisingly complex and accurate transduction of visual information. To achieve precision, a multilayered neuroglia structure is established throughout the embryonic development, and the presence of radial Müller (glial) cells ensure differentiation, growth and survival for the neuronal elements within retinal environment. It is assumed that Müller cells serve as a dynamic reservoir of progenitors, capable of expressing transcription factors, differentiating and proliferating as either neuronal or glial cells depending on extrinsic cues. In the postnatal period, Müller glia may re-enter cell cycle and produce new retinal neurons in response to acute damage. In this context, glutathione (GSH), a virtually ubiquitous tripeptide antioxidant, which is found at milimolar concentrations in central glial cells, plays a vital role as a reducing agent, buffering radical oxygen species (ROS) and preventing cell death in severely injured retinal tissues. Despite its antioxidant role, data also point to GSH as a signaling agent, suggesting that GABA release and P2X7R-mediated calcium inwards occur in Müller cells in a GSH-enriched environment. These phenomena indicate a novel mechanistic response to damage in the vertebrate retinal tissue, particularly in neuron-glia networks.

  6. Elucidating the Foundations of Statistical Inference with 2 x 2 Tables

    PubMed Central

    Choi, Leena; Blume, Jeffrey D.; Dupont, William D.

    2015-01-01

    To many, the foundations of statistical inference are cryptic and irrelevant to routine statistical practice. The analysis of 2 x 2 contingency tables, omnipresent in the scientific literature, is a case in point. Fisher's exact test is routinely used even though it has been fraught with controversy for over 70 years. The problem, not widely acknowledged, is that several different p-values can be associated with a single table, making scientific inference inconsistent. The root cause of this controversy lies in the table's origins and the manner in which nuisance parameters are eliminated. However, fundamental statistical principles (e.g., sufficiency, ancillarity, conditionality, and likelihood) can shed light on the controversy and guide our approach in using this test. In this paper, we use these fundamental principles to show how much information is lost when the tables origins are ignored and when various approaches are used to eliminate unknown nuisance parameters. We present novel likelihood contours to aid in the visualization of information loss and show that the information loss is often virtually non-existent. We find that problems arising from the discreteness of the sample space are exacerbated by p-value-based inference. Accordingly, methods that are less sensitive to this discreteness - likelihood ratios, posterior probabilities and mid-p-values - lead to more consistent inferences. PMID:25849515

  7. First passage times in M2[X ]|G |1 |R queue with hysteretic overload control policy

    NASA Astrophysics Data System (ADS)

    Pechinkin, Alexander V.; Razumchik, Rostislav R.; Zaryadov, Ivan S.

    2016-06-01

    One of the reported approaches towards the solution of overload problem in networks of SIP servers is the implementation of multi-level hysteretic control of arrivals in SIP servers. Each level, being the parameter of the policy, specifies operation mode of SIP server i.e. it implicitly indicates what SIP server must do with the arriving packets. The choice of parameters' values is not guided by standards and is usually left for the network owner. In general, all operation modes of the considered policy can be grouped into two groups: normal mode (when all arriving packets are accepted) and congested mode (when part or all arriving packets are being dropped). Such grouping may serve as the criteria for choosing parameters' values of the policy: pick those values which minimize SIP server sojourn time in congested mode. In this short note we propose some analytical results which facilitate the solution of stated minimization problem. The considered mathematical model of SIP server is the queueing system M2[X ]|G |1 |R with batch arrivals and bi-level hysteretic control policy, which specifies three operation modes: normal (customers both flows are accepted), overload (only customers from one flow are accepted), discard (customers from both flows are blocked/lost)). The switching between modes can occur only on service completions. Analytical method allowing computation of stationary sojourn times in different operation modes (as well as first passage times between modes) is presented in brief. Numerical example is given.

  8. Structural Studies of CH_3SiF_2-X (x = Nco, Cl) by Microwave Spectroscopy

    NASA Astrophysics Data System (ADS)

    Guirgis, Gamil A.; Gause, Korreda K.; Seifert, Nathan A.; Zaleski, Daniel P.; Pate, Brooks H.; Palmer, Michael H.; Peebles, Rebecca A.; Peebles, Sean A.; Elmuti, Lena F.; Obenchain, Daniel A.

    2012-06-01

    The structures of CH_3SiF_2-NCO and CH_3SiF_2-Cl have been studied by molecular rotational spectroscopy in the 6.5-18 GHz band. The rotational spectrum was measured by cavity Fourier transform microwave (FTMW) and chirped-pulse FTMW spectroscopy. The experiment targeted the study of CH_3SiF_2-NCO, but CH_3SiF_2-Cl was also observed as an impurity. Due to the dynamic range achieved on these spectra, all isotopologs with natural abundance ≥0.2% were assigned, which includes two doubly-substituted isotopologs for the chloride (29Si/37Cl and 30Si/37Cl). Strategies for obtaining the molecular structure for these two molecules using either a Kraitchman analysis (to obtain a partial substitution structure) or r_0 analysis (with additional constraints on the structure supplied by the theoretical structure) will be discussed. Derived structural parameters for the CH_3-SiF_2-X base structure are the same for the two compounds. The hyperfine and internal rotation effects in the spectra have been analyzed for all isotopologs and the Hamiltonian parameters are in very good agreement with ab initio results. The barriers to methyl group internal rotation for the two compounds 446(50) cm-1 and 463(3) cm-1 and are independent of the isotopic structure of the heavy atom frame.

  9. Ferrimagnetism and disorder of epitaxial Mn2-xCoxVAl Heusler compound thin films

    SciTech Connect

    Meinert, Markus; Schmalhorst, Jan-Michael; Reiss, Gunter; Arenholz, Elke

    2011-01-29

    The quaternary full Heusler compound Mn{sub 2-x}Co{sub x}VAl with x = 1 is predicted to be a half-metallic antiferromagnet. Thin films of the quaternary compounds with x = 0-2 were prepared by dc and RF magnetron co-sputtering on heated MgO (0 0 1) substrates. The magnetic structure was examined by x-ray magnetic circular dichroism and the chemical disorder was characterized by x-ray diffraction. Ferrimagnetic coupling of V to Mn was observed for Mn{sub 2}VAl (x = 0). For x = 0.5, we also found ferrimagnetic order with V and Co antiparallel to Mn. The observed reduced magnetic moments are interpreted with the help of band structure calculations in the coherent potential approximation. Mn{sub 2}VAl is very sensitive to disorder involving Mn, because nearest-neighbour Mn atoms couple antiferromagnetically. Co{sub 2}VAl has B2 order and has reduced magnetization. In the cases with x {ge} 0.9 conventional ferromagnetism was observed, closely related to the atomic disorder in these compounds.

  10. Thermoelectric properties of the Ca(5)Al(2-x)In(x)Sb(6) solid solution.

    PubMed

    Zevalkink, Alex; Swallow, Jessica; Ohno, Saneyuki; Aydemir, Umut; Bux, Sabah; Snyder, G Jeffrey

    2014-11-14

    Zintl phases are attractive for thermoelectric applications due to their complex structures and bonding environments. The Zintl compounds Ca(5)Al(2)In(x)Sb(6)and Ca(5)Al(2)In(x)Sb(6) have both been shown to have promising thermoelectric properties, with zT values of 0.6 and 0.7, respectively, when doped to control the carrier concentration. Alloying can often be used to further improve thermoelectric materials in cases when the decrease in lattice thermal conductivity outweighs reductions to the electronic mobility. Here we present the high temperature thermoelectric properties of the Ca(5)Al(2-x)In(x)Sb(6)solid solution. Undoped and optimally Zn-doped samples were investigated. X-ray diffraction confirms that a full solid solution exists between the Al and In end-members. We find that the Al : In ratio does not greatly influence the carrier concentration or Seebeck effect. The primary effect of alloying is thus increased scattering of both charge carriers and phonons, leading to significantly reduced electronic mobility and lattice thermal conductivity at room temperature. Ultimately, the figure of merit is unaffected by alloying in this system, due to the competing effects of reduced mobility and lattice thermal conductivity.

  11. Molecular modeling of alkyl monolayers on the Si(100)-2 x 1 surface.

    PubMed

    Lee, Michael V; Guo, Dawei; Linford, Matthew R; Zuilhof, Han

    2004-10-12

    Molecular modeling was used to simulate various surfaces derived from the addition of 1-alkenes and 1-alkynes to Si=Si dimers on the Si(100)-2 x 1 surface. The primary aim was to better understand the interactions between adsorbates on the surface and distortions of the underlying silicon crystal due to functionalization. Random addition of ethylene and acetylene was used to determine how the addition of an adduct molecule affects subsequent additions for coverages up to one molecule per silicon dimer, that is, 100% coverage. Randomization subdues the effect that the relative positions of the adsorbates have on the enthalpy of the system. For ethylene and acetylene, the enthalpy of reaction changes less than 3 and 5 kcal/mol, respectively, from the first reacted species up to 100% coverage. As a result, a (near-)complete coverage is predicted, which is in line with experimental data. When 1-alkenes and 1-alkynes add by [2 + 2] addition, the hydrocarbon chains interact differently depending on the direction they project from the surface. These effects were investigated for four-carbon chains: 1-butene and 1-butyne. As expected, the chains that would otherwise intersect bend to avoid each other, raising the enthalpy of the system. For alkyl chains longer than four carbons, the chains are able to reorient themselves in a favorable manner, thus, resulting in a steady reduction in reaction enthalpy of about 2 kcal/mol for each additional methylene unit.

  12. Direct proof of static charge stripe correlations in La2-xBaxCuO4

    NASA Astrophysics Data System (ADS)

    Chen, X. M.; Thampy, V.; Mazzoli, C.; Barbour, A.; Gu, G.; Hill, J. P.; Tranquada, J. M.; Dean, M. P. M.; Wilkins, S. B.

    The nature of charge stripe order in the cuprates, and in particular whether the stripes are static or dynamic, is a key issue in understanding the relationship between stripes and superconductivity. In La2-xBaxCuO4 (LBCO) a low temperature structural distortion is widely believed to pin stripes into fixed, static domains, but such an assertion has never been directly verified. We performed resonant soft x-ray photon correlation spectroscopy (XPCS) to probe the charge order Bragg peak of 1/8 doped LBCO. At low temperatures, we observe time-independent x-ray speckle patterns persisting for more than three hours, proving the static nature of the stripes and we go on to discuss how stripe order melts with increasing temperature. Our results demonstrate that the combination of XPCS with diffraction limited light sources such as the National Synchrotron Light Source II can probe the dynamics of even subtle order parameters such as stripes in the cuprates. Work performed at Brookhaven National Laboratory was supported by the US Department of Energy, Division of Materials Science, under Contract No. DE-AC02-98CH10886. Use of the National Synchrotron Light Source II was supported under Contract No. DE-SC0012704.

  13. Stripe order in La2-xBaxCuO4 at ambient and high pressure.

    NASA Astrophysics Data System (ADS)

    Huecker, M.; Wen, J. S.; Xu, Z. J.; Gu, G. D.; Tranquada, J. M.; Zimmermann, M. V.

    2009-03-01

    The pronounced stability of the charge and spin stripe order in La2-xBaxCuO4 at x=1/8 doping still is a poorly understood peculiarity. A combination of electronic and structural interactions is likely, however it has been difficult to clearly separate the involved mechanisms. One approach is to explore how stripe order fades away for dopings x !=1/8. We have performed high energy (100 keV) x-ray diffraction and static magnetization experiments on single crystals between x=0.095 and 0.155. To our surprise, at ambient pressure stripes exist in a much broader range of doping around x=1/8 than expected. In the underdoped region charge stripe order always coincides with a structural transition associated with a rotation of the octahedral tilt axis. However, for x=1/8 and high pressure we have been able to show that stripe order also occurs in the absence of this structural phase, which motivates us to discuss stripes in terms of an electronic liquid crystal phase.

  14. Structure and electronic properties of ZnxSn1-xO2-x

    NASA Astrophysics Data System (ADS)

    Roy, Anindya; Jin, Yansha; Jiang, Tonghu; Falk, Michael

    2014-03-01

    Using first-principles based hybrid-exchange calculations we look at the structural and electronic properties of Zn-Sn-O system. The oxides represented by ZnxSn1-xO2-x has end members ZnO and SnO2. These relatively well studied, native n-type semiconductors are technologically important. Intermediate oxides corresponding to x = 2/3 and 1/2 have been synthesized: spinel Zn2SnO4 and rhombohedral ZnSnO3. These mixed oxides are functionally promising for their potential as ferroelectrics, transparent conducting oxides, thermoelectrics etc. Previously, ab initio calculations investigated the structures, electronic and thermodynamic properties of these mixed oxides. However, we considerably improve our understanding of band gap values and band structure of these compounds using hybrid-exchange method. We also perform band alignment calculations, estimate work function of these intermediate oxides, and compare those values to that of the end members and to the experimental results. The existence of Zn2SnO4 in the spinel structure allows a number of configurations which correspond to normal, partially inverted, or inverted spinel forms. We use cluster expansion method to identify energetically most stable form before calculating other properties.

  15. Photoelectric properties of defect chalcogenide HgGa2X4 (x=S, Se, Te)

    NASA Astrophysics Data System (ADS)

    Sharma, Ramesh; Dwivedi, Shalini; Sharma, Yamini

    2016-05-01

    We present results of ab initio study of ordered vacancy compounds of mercury. The electronic structure, charge density, optical and transport properties of the semiconductor family HgGa2X4 (X=S, Se, Te) are calculated using the full potential linearized augmented plane wave method which is based on the density functional theory. A direct bandgap is observed in these compounds, which reduces in the order S>Se>Te. From the density of states it is observed that there is strong hybridization of Hg-d, Ga-d and X-p states. The optical properties show a red shift with increasing size and atomic no. of the chalcogenide atoms. We have also reported the transport properties of mercury thiogallates for the first time. The selenide compound exhibits n-type nature whereas HgGa2S4 and HgGa2Te4 show p-type behavior. The power factor and ZT for the HGS increases at low temperatures, the figure of merit is highest for HgGa2Se4 (1.17) at 19 K.

  16. Electronic structure of titanium dichalcogenides TiX{sub 2} (X = S, Se, Te)

    SciTech Connect

    Shkvarin, A. S. Yarmoshenko, Yu. M.; Skorikov, N. A.; Yablonskikh, M. V.; Merentsov, A. I.; Shkvarina, E. G.; Titov, A. N.

    2012-01-15

    The electronic structure and the chemical bond in titanium dichalcogenides TiX{sub 2} (X = S, Se, Te), which are promising electrode materials for lithium batteries, are studied experimentally and theoretically. It is found that the X-ray photoelectron spectra of the valence bands and the core levels of titanium and its X-ray L{sub 2,3} absorption spectra demonstrate a change in the ionic and covalent components of the chemical bond in these compounds. The densities of states in these compounds are calculated by the full-potential augmented-plane-wave method, and multiplet calculations of the X-ray L{sub 2,3} absorption spectra of titanium are performed. It is shown that, in the row TiS{sub 2}-TiSe{sub 2}-TiTe{sub 2}, the covalence increases, the ionicity of the chemical bond decreases, and the effect of the crystal field of a ligand is weakened.

  17. Correlating Carrier Density and Emergent Plasmonic Features in Cu2-xSe Nanoparticles.

    PubMed

    Marbella, Lauren E; Gan, Xing Yee; Kaseman, Derrick C; Millstone, Jill E

    2017-03-17

    Recently, a wide variety of new nanoparticle compositions have been identified as potential plasmonic materials including earth-abundant metals such as aluminum, highly doped semiconductors, as well as metal pnictides. For semiconductor compositions, plasmonic properties may be tuned not only by nanoparticle size and shape, but also by charge carrier density which can be controlled via a variety of intrinsic and extrinsic doping strategies. Current methods to quantitatively determine charge carrier density primarily rely on interpretation of the nanoparticle extinction spectrum. However, interpretation of nanoparticle extinction spectra can be convoluted by factors such as particle ligands, size distribution and/or aggregation state which may impact the charge carrier information extracted. Therefore, alternative methods to quantify charge carrier density may be transformational in the development of these new materials and would facilitate previously inaccessible correlations between particle synthetic routes, crystallographic features, and emergent optoelectronic properties. Here, we report the use of (77)Se solid state nuclear magnetic resonance (NMR) spectroscopy to quantitatively determine charge carrier density in a variety of Cu2-xSe nanoparticle compositions and correlate this charge carrier density with particle crystallinity and extinction features. Importantly, we show that significant charge carrier populations are present even in nanoparticles without spectroscopically discernible plasmonic features and with crystal structures indistinguishable from fully reduced Cu2Se. These results highlight the potential impact of the NMR-based carrier density measurement, especially in the study of plasmon emergence in these systems (i.e., at low dopant concentrations).

  18. Pore architecture and ion sites in acid-sensing ion channels and P2X receptors.

    PubMed

    Gonzales, Eric B; Kawate, Toshimitsu; Gouaux, Eric

    2009-07-30

    Acid-sensing ion channels are proton-activated, sodium-selective channels composed of three subunits, and are members of the superfamily of epithelial sodium channels, mechanosensitive and FMRF-amide peptide-gated ion channels. These ubiquitous eukaryotic ion channels have essential roles in biological activities as diverse as sodium homeostasis, taste and pain. Despite their crucial roles in biology and their unusual trimeric subunit stoichiometry, there is little knowledge of the structural and chemical principles underlying their ion channel architecture and ion-binding sites. Here we present the structure of a functional acid-sensing ion channel in a desensitized state at 3 A resolution, the location and composition of the approximately 8 A 'thick' desensitization gate, and the trigonal antiprism coordination of caesium ions bound in the extracellular vestibule. Comparison of the acid-sensing ion channel structure with the ATP-gated P2X(4) receptor reveals similarity in pore architecture and aqueous vestibules, suggesting that there are unanticipated yet common structural and mechanistic principles.

  19. Spin Start Line Effects on the J2X Gas Generator Chamber Acoustics

    NASA Technical Reports Server (NTRS)

    Kenny, R. Jeremy

    2011-01-01

    The J2X Gas Generator engine design has a spin start line connected near to the turbine inlet vanes. This line provides helium during engine startup to begin turbomachinery operation. The spin start line also acts as an acoustic side branch which alters the chamber's acoustic modes. The side branch effectively creates 'split modes' in the chamber longitudinal modes, in particular below the first longitudinal mode and within the frequency range associated with the injection-coupled response of the Gas Generator. Interaction between the spin start-modified chamber acoustics and the injection-driven response can create a higher system response than without the spin start attached to the chamber. This work reviews the acoustic effects of the spin start line as seen throughout the workhorse gas generator test program. A simple impedance model of the spin start line is reviewed. Tests were run with no initial spin start gas existing in the line, as well as being initially filled with nitrogen gas. Tests were also run with varying spin start line lengths from 0" to 40". Acoustic impedance changes due to different spin start gas constituents and line lengths are shown. Collected thermocouple and static pressure data in the spin start line was used to help estimate the fluid properties along the line length. The side branch impedance model was coupled to a chamber impedance model to show the effects on the overall chamber response. Predictions of the spin start acoustic behavior for helium operation are shown and compared against available data.

  20. Nematic Quantum Critical Fluctuations in BaFe_{2-x}Ni_{x}As_{2}.

    PubMed

    Liu, Zhaoyu; Gu, Yanhong; Zhang, Wei; Gong, Dongliang; Zhang, Wenliang; Xie, Tao; Lu, Xingye; Ma, Xiaoyan; Zhang, Xiaotian; Zhang, Rui; Zhu, Jun; Ren, Cong; Shan, Lei; Qiu, Xianggang; Dai, Pengcheng; Yang, Yi-Feng; Luo, Huiqian; Li, Shiliang

    2016-10-07

    We have systematically studied the nematic fluctuations in the electron-doped iron-based superconductor BaFe_{2-x}Ni_{x}As_{2} by measuring the in-plane resistance change under uniaxial pressure. While the nematic quantum critical point can be identified through the measurements along the (110) direction, as studied previously, quantum and thermal critical fluctuations cannot be distinguished due to similar Curie-Weiss-like behaviors. Here we find that a sizable pressure-dependent resistivity along the (100) direction is present in all doping levels, which is against the simple picture of an Ising-type nematic model. The signal along the (100) direction becomes maximum at optimal doping, suggesting that it is associated with nematic quantum critical fluctuations. Our results indicate that thermal fluctuations from striped antiferromagnetic order dominate the underdoped regime along the (110) direction. We argue that either there is a strong coupling between the quantum critical fluctuations and the fermions, or more exotically, a higher symmetry may be present around optimal doping.

  1. A new approach for deriving the solar irradiance from non-flaring solar upper atmosphere plasmas at 2 x 10^4<-T<-2 x 10^7 K

    SciTech Connect

    Colgan, James P; Abdallaf, Jr., Joseph; Fontes, Christopher J; Sherrill, Manolo E; Feldmn, U; Landi, E; Brown, C M; Seely, J F; Doschek, G A; Dammasch, I E

    2008-01-01

    We propose a new approach for deriving the solar irradiance in the X-ray to VUV range due to the emission by solar upper atmosphere plasmas at 2 x 10{sup 4} {le} T {le} 2 x 10{sup 7} K. Our approach is based on new understanding of the properties of the solar upper atmosphere; specifically, the discovery that the majority of emission from the non-flaring solar upper transition region and corona in the temperature range 3 x 10{sup 5} {le} T {le} 3 x 10{sup 6} K arises from isothermal plasmas that have four distinct temperatures: 0.35, 0.9, 1.4 and 3 x 10{sup 6} K. In the lower transition region (2 x 10{sup 4} {le} T {le} 2 x 10{sup 5} K) of coronal holes, quiet regions or active regions, although multithermal and variable in brightness, the shape of emission measure vs. temperature curves is almost constant. Flaring plasmas are for most part isothermal, although their emission measure and temperature continuously change. In this paper we review these recent results and propose a set of simple spectrometers for recording the solar spectrum in several narrow bands. The solar emission measure, average plasma temperature, and composition can be derived using the measured line fluxes. By combining the emission measure and other plasma properties with the output of a suite of atomic physics codes, which are also described here, the solar irradiance in the temperature range 2 x 10{sup 4} {le} T {le} 2 x 10{sup 7} K can be calculated.

  2. Discovery of new ferroelectrics: [H2dbco]2 x [Cl3] x [CuCl3(H2O)2] x H2O (dbco = 1,4-Diaza-bicyclo[2.2.2]octane).

    PubMed

    Zhang, Wen; Ye, Heng-Yun; Cai, Hong-Ling; Ge, Jia-Zhen; Xiong, Ren-Gen; Huang, Songping D

    2010-06-02

    Compound [H(2)dbco](2) x [Cl(3)] x [CuCl(3)(H(2)O)(2)] x H(2)O undergoes a sharp dielectric anomaly and a paraelectric-to-ferroelectric phase transition at approximately -23 degrees C with a spontaneous polarization of 1.04 microC cm(-2), being the first molecular metal coordination compound ferroelectrics with a large dielectric response involving a 2 orders of magnitude enhancement and distinct Curie phase transition point. This work has proved an effective way for exploration of new ferroelectrics based on a five-coordinated divalent metal through the combination of crystal engineering and Landau phase transition theory.

  3. Sequential evolution of different phases in metastable Gd(2-x)Ce(x)Zr(2-x)Al(x)O7 (0.0 ≤ x ≤ 2.0) system: crucial role of reaction conditions.

    PubMed

    Shukla, Rakesh; Sayed, Farheen N; Phapale, Suhas; Mishra, Ratikant; Tyagi, Avesh K

    2013-07-15

    The Gd(2-x)Ce(x)Zr(2-x)Al(x)O7 (0.0 ≤ x ≤ 2.0) series was synthesized by the gel combustion method. This system exhibited the presence of a fluorite-type phase, along with a narrow biphasic region, depending upon the Ce/Gd content in the sample. Thermal stability of these new compounds under oxidizing and reducing conditions has been investigated. The products obtained on decomposition of Gd(2-x)Ce(x)Zr(2-x)Al(x)O7 in oxidizing and reducing conditions were found to be entirely different. It was observed that in air the fluorite-type solid solutions of Gd(2-x)Ce(x)Zr(2-x)Al(x)O7 composition undergo phase separation into perovskite GdAlO3 and fluorite-type solid solutions of Gd-Ce-Zr-O or Ce-Zr-Al-O depending upon the extent of Ce and Al substitution. On the other hand, Gd(2-x)Ce(x)Zr(2-x)Al(x)O7 samples on heating under reducing conditions show a phase separation to CeAlO3 perovskite and a defect-fluorite of Gd2Zr2O7. The extent of metastability for a typical composition of Gd(1.2)Ce(0.8)Zr(1.2)Al(0.8)O7 (nano), Gd(1.2)Ce(0.8)Zr(1.2)Al(0.8)O(6.6) (heated under reduced conditions), Gd(1.2)Ce(0.8)Zr(1.2)Al(0.8)O7 (heated in air at 1200 °C) has been experimentally determined employing a high temperature Calvet calorimeter. On the basis of thermodynamic stability data, it could be inferred that the formation of a more stable compound in the presence of tw