Sample records for kappa distributed electrons

  1. Nonplanar ion acoustic waves with kappa-distributed electrons

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sahu, Biswajit

    2011-06-15

    Using the standard reductive perturbation technique, nonlinear cylindrical and spherical Kadomtsev-Petviashvili equations are derived for the propagation of ion acoustic solitary waves in an unmagnetized collisionless plasma with kappa distributed electrons and warm ions. The influence of kappa-distributed electrons and the effects caused by the transverse perturbation on cylindrical and spherical ion acoustic waves (IAWs) are investigated. It is observed that increase in the kappa distributed electrons (i.e., decreasing {kappa}) decreases the amplitude of the solitary electrostatic potential structures. The numerical results are presented to understand the formation of ion acoustic solitary waves with kappa-distributed electrons in nonplanar geometry. Themore » present investigation may have relevance in the study of propagation of IAWs in space and laboratory plasmas.« less

  2. Characterizing Cometary Electrons with Kappa Distributions

    NASA Technical Reports Server (NTRS)

    Broiles, T. W.; Livadiotis, G.; Burch, J. L.; Chae, K.; Clark, G.; Cravens, T. E.; Davidson, R.; Eriksson, A.; Frahm, R. A.; Fuselier, S. A.; hide

    2016-01-01

    The Rosetta spacecraft has escorted comet 67P/Churyumov-Gerasimenko since 6 August 2014 and has offered an unprecedented opportunity to study plasma physics in the coma. We have used this opportunity to make the first characterization of cometary electrons with kappa distributions. Two three-dimensional kappa functions were fit to the observations, which we interpret as two populations of dense and warm (density 10 cubic centimeters, temperature 2 times 10 (sup 5) degrees Kelvin, invariant kappa index 10 to 1000), and rarefied and hot (density equals 0.005 cubic centimeters, temperature 5 times 10 (sup 5) degrees Kelvin, invariant kappa index equals 1 to 10) electrons. We fit the observations on 30 October 2014 when Rosetta was 20 kilometers from 67P, and 3 Astronomical Units from the Sun. We repeated the analysis on 15 August 2015 when Rosetta was 300 kilometers from the comet and 1.3 Astronomical Units from the Sun. Comparing the measurements on both days gives the first comparison of the cometary electron environment between a nearly inactive comet far from the Sun and an active comet near perihelion. We find that the warm population density increased by a factor of 3, while the temperature cooled by a factor of 2, and the invariant kappa index was unaffected. We find that the hot population density increased by a factor of 10, while the temperature and invariant kappa index were unchanged. We conclude that the hot population is likely the solar wind halo electrons in the coma. The warm population is likely of cometary origin, but its mechanism for production is not known.

  3. Ion and electron Kappa distribution functions in the plasma sheet.

    NASA Astrophysics Data System (ADS)

    Moya, P. S.; Stepanova, M. V.; Espinoza, C.; Antonova, E. E.; Valdivia, J. A.

    2017-12-01

    We present a study of ion and electron flux spectra in the Earth's plasma sheet using kappa distribution functions. Satellite data from the THEMIS mission were collected for thousands of crossings through the plasma sheet, between 7 and 35 Re and during the years 2008-2009. The events were separated according to the geomagnetic activity at the time. Our results show the distribution of the kappa index and characteristic energies across the plasma sheet and its evolution with distance to Earth for quiet times and for the substorm expansion and recovery phases. For the ions, it is observed that the kappa values tend to decrease outwards and that this effect is more significant in the dusk sector, where the smallest values are found for distances beyond 15 Re. The main effect of the substorms appears as an enhancement of this behavior. The electrons show a much more homogeneous distribution in quiet times, with a mild tendency for larger kappa values at larger distances. During substorms, the kappa values tend to equalize and appear very homogenous during expansion. However, they exhibit a significant increase in the dusk sector during the recovery substorm phase. Finally, we observe that the characteristic energy of the particles during substorms increases and concentrate at distances less than 15 Re.

  4. Kappa-Electrons Downstream of the Solar Wind Termination Shock

    NASA Astrophysics Data System (ADS)

    Fahr, H. J.

    2017-12-01

    A theoretical description of the solar wind electron distribution function downstream of the termination shock under the influence of the shock-induced injection of overshooting KeV-energetic electrons will be presented. A kinetic phasespace transport equation in the bulk frame of the heliosheath plasma flow is developed for the solar wind electrons, taking into account shock-induced electron injection, convective changes, magnetic cooling processes and whistler wave-induced energy diffusion. Assuming that the local electron distribution under the prevailing Non-LTE conditions can be represented by a local kappa function with a local kappa parameter that varies with the streamline coordinates, we determine the parameters of the resulting, initial kappa distribution for the downstream electrons. From this initial function spectral electron fluxes can be derived and can be compared with those measured by the VOYAGER-1 spacecraft in the range between 40 to 70 KeV. It can then be shown that with kappa values around kappa = 6 one can in fact fit these data very satisfactorily. In addition it is shown that for isentropic electron flows kappa-distributed electrons have to undergo simultaneous changes of both parameters, i.e. kappa and theta, of the electron kappa function. It is also shown then that under the influence of energy sinks and sources the electron flux becomes non-isentropic with electron entropies changing along the streamline.

  5. Kinetic study of ion acoustic twisted waves with kappa distributed electrons

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Arshad, Kashif, E-mail: kashif.arshad.butt@gmail.com; Aman-ur-Rehman, E-mail: amansadiq@gmail.com; Mahmood, Shahzad, E-mail: shahzadm100@gmail.com

    2016-05-15

    The kinetic theory of Landau damping of ion acoustic twisted modes is developed in the presence of orbital angular momentum of the helical (twisted) electric field in plasmas with kappa distributed electrons and Maxwellian ions. The perturbed distribution function and helical electric field are considered to be decomposed by Laguerre-Gaussian mode function defined in cylindrical geometry. The Vlasov-Poisson equation is obtained and solved analytically to obtain the weak damping rates of the ion acoustic twisted waves in a non-thermal plasma. The strong damping effects of ion acoustic twisted waves at low values of temperature ratio of electrons and ions aremore » also obtained by using exact numerical method and illustrated graphically, where the weak damping wave theory fails to explain the phenomenon properly. The obtained results of Landau damping rates of the twisted ion acoustic wave are discussed at different values of azimuthal wave number and non-thermal parameter kappa for electrons.« less

  6. Ion-cyclotron instability in plasmas described by product-bi-kappa distributions

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Santos, M. S. dos; Ziebell, L. F., E-mail: luiz.ziebell@ufrgs.br; Gaelzer, R., E-mail: rudi.gaelzer@ufrgs.br

    The dispersion relation for parallel propagating waves in the ion-cyclotron branch is investigated numerically by considering that the velocity distribution of the ion population is a function of type product-bi-kappa. We investigate the effects of the non-thermal features and of the anisotropy associated with this type of distribution on the ion-cyclotron instability, as well as the influence of different forms of the electron distribution, by considering Maxwellian distributions, bi-kappa distributions, and product-bi-kappa distributions. The cases of ions described by either Maxwellian or bi-kappa distributions are also considered, for comparison. The results of the numerical analysis show that the increase inmore » the non-thermal character associated with the anisotropic kappa distributions for ions contributes to enhance the instability as compared to that obtained in the Maxwellian case, in magnitude and in wave number range, with more significant enhancement for the case of ion product-bi-kappa distributions than for the case of ion bi-kappa distributions. It is also shown that the ion-cyclotron instability is decreased if the electrons are described by product-bi-kappa distributions, while electrons described by bi-kappa distributions lead to growth rates which are very similar to those obtained considering a Maxwellian distribution for the electron population.« less

  7. Slow test charge response in a dusty plasma with Kappa distributed electrons and ions

    NASA Astrophysics Data System (ADS)

    Ali, S.; Eliasson, B.

    2017-08-01

    The electrostatic potential around a slowly moving test charge is studied in a dusty plasma where the ions and electrons follow a powerlaw Kappa distribution in velocity space. A test charge moving with a speed much smaller than the dust thermal speed gives rise to a short-scale Debye-Hückel potential as well as a long-range far-field potential decreasing as inverse cube of the distance to the test charge along the propagation direction. The potentials are significantly modified in the presence of high-energy tails, modeled by lower spectral indices in the ion and electron Kappa distribution functions. Plasma parameters relevant to laboratory dusty plasmas are discussed.

  8. Nonequilibrium approach regarding metals from a linearised kappa distribution

    NASA Astrophysics Data System (ADS)

    Domenech-Garret, J. L.

    2017-10-01

    The widely used kappa distribution functions develop high-energy tails through an adjustable kappa parameter. The aim of this work is to show that such a parameter can itself be regarded as a function, which entangles information about the sources of disequilibrium. We first derive and analyse an expanded Fermi-Dirac kappa distribution. Later, we use this expanded form to obtain an explicit analytical expression for the kappa parameter of a heated metal on which an external electric field is applied. We show that such a kappa index causes departures from equilibrium depending on the physical magnitudes. Finally, we study the role of temperature and electric field on such a parameter, which characterises the electron population of a metal out of equilibrium.

  9. Landau damping of Langmuir twisted waves with kappa distributed electrons

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Arshad, Kashif, E-mail: kashif.arshad.butt@gmail.com; Aman-ur-Rehman; Mahmood, Shahzad

    2015-11-15

    The kinetic theory of Landau damping of Langmuir twisted modes is investigated in the presence of orbital angular momentum of the helical (twisted) electric field in plasmas with kappa distributed electrons. The perturbed distribution function and helical electric field are considered to be decomposed by Laguerre-Gaussian mode function defined in cylindrical geometry. The Vlasov-Poisson equation is obtained and solved analytically to obtain the weak damping rates of the Langmuir twisted waves in a nonthermal plasma. The strong damping effects of the Langmuir twisted waves at wavelengths approaching Debye length are also obtained by using an exact numerical method and aremore » illustrated graphically. The damping rates of the planar Langmuir waves are found to be larger than the twisted Langmuir waves in plasmas which shows opposite behavior as depicted in Fig. 3 by J. T. Mendoça [Phys. Plasmas 19, 112113 (2012)].« less

  10. Ion acoustic shock waves in plasmas with warm ions and kappa distributed electrons and positrons

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hussain, S.; Mahmood, S.; Hafeez Ur-Rehman

    2013-06-15

    The monotonic and oscillatory ion acoustic shock waves are investigated in electron-positron-ion plasmas (e-p-i) with warm ions (adiabatically heated) and nonthermal kappa distributed electrons and positrons. The dissipation effects are included in the model due to kinematic viscosity of the ions. Using reductive perturbation technique, the Kadomtsev-Petviashvili-Burgers (KPB) equation is derived containing dispersion, dissipation, and diffraction effects (due to perturbation in the transverse direction) in e-p-i plasmas. The analytical solution of KPB equation is obtained by employing tangent hyperbolic (Tanh) method. The analytical condition for the propagation of oscillatory and monotonic shock structures are also discussed in detail. The numericalmore » results of two dimensional monotonic shock structures are obtained for graphical representation. The dependence of shock structures on positron equilibrium density, ion temperature, nonthermal spectral index kappa, and the kinematic viscosity of ions are also discussed.« less

  11. Mechanisms generating kappa distributions in plasmas

    NASA Astrophysics Data System (ADS)

    Livadiotis, Georgios

    2017-10-01

    Kappa distributions have become increasingly widespread across plasma physics. Publication records reveal an exponential growth of papers relevant to kappa distributions. However, the vast majority of publications refer to statistical fits and applications of these distributions in plasmas. Up to date, there is no systematic analysis on the origin of kappa distributions, that is, the mechanisms that can generate kappa distributions in plasmas. The general scheme that characterizes these mechanisms is composed of two parts: (1) the generation of local correlations among particles, and (2) the thermalization, that is, the stabilization of the particle system into stationary states described by kappa distributions or combinations thereof. Several mechanisms are known in the literature, each characterized by a specific relationship between the plasma properties. These relationships serve as conditions that need to be fulfilled for the corresponding mechanisms to be applied in the plasma. Using these relationships, we identify three mechanisms that generate kappa distributions in the solar wind plasma: (i) Debye shielding, (ii) magnetic field binding, and (iii) thermal fluctuations, each one prevailing in different scales of the solar wind plasma and magnetic field properties. The work was supported in part by the project NNX17AB74G of NASA's HGI Program.

  12. Dust ion-acoustic shock waves in magnetized pair-ion plasma with kappa distributed electrons

    NASA Astrophysics Data System (ADS)

    Kaur, B.; Singh, M.; Saini, N. S.

    2018-01-01

    We have performed a theoretical and numerical analysis of the three dimensional dynamics of nonlinear dust ion-acoustic shock waves (DIASWs) in a magnetized plasma, consisting of positive and negative ion fluids, kappa distributed electrons, immobile dust particulates along with positive and negative ion kinematic viscosity. By employing the reductive perturbation technique, we have derived the nonlinear Zakharov-Kuznetsov-Burgers (ZKB) equation, in which the nonlinear forces are balanced by dissipative forces (associated with kinematic viscosity). It is observed that the characteristics of DIASWs are significantly affected by superthermality of electrons, magnetic field strength, direction cosines, dust concentration, positive to negative ions mass ratio and viscosity of positive and negative ions.

  13. Origins and properties of kappa distributions in space plasmas

    NASA Astrophysics Data System (ADS)

    Livadiotis, George

    2016-07-01

    Classical particle systems reside at thermal equilibrium with their velocity distribution function stabilized into a Maxwell distribution. On the contrary, collisionless and correlated particle systems, such as the space and astrophysical plasmas, are characterized by a non-Maxwellian behavior, typically described by the so-called kappa distributions. Empirical kappa distributions have become increasingly widespread across space and plasma physics. However, a breakthrough in the field came with the connection of kappa distributions to the solid statistical framework of Tsallis non-extensive statistical mechanics. Understanding the statistical origin of kappa distributions was the cornerstone of further theoretical developments and applications, some of which will be presented in this talk: (i) The physical meaning of thermal parameters, e.g., temperature and kappa index; (ii) the multi-particle description of kappa distributions; (iii) the phase-space kappa distribution of a Hamiltonian with non-zero potential; (iv) the Sackur-Tetrode entropy for kappa distributions, and (v) the new quantization constant, h _{*}˜10 ^{-22} Js.

  14. Generation of Kappa Distributions in Solar Wind at 1 au

    NASA Astrophysics Data System (ADS)

    Livadiotis, G.; Desai, M. I.; Wilson, L. B., III

    2018-02-01

    We examine the generation of kappa distributions in the solar wind plasma near 1 au. Several mechanisms are mentioned in the literature, each characterized by a specific relationship between the solar wind plasma features, the interplanetary magnetic field (IMF), and the kappa index—the parameter that governs the kappa distributions. This relationship serves as a signature condition that helps the identification of the mechanism in the plasma. In general, a mechanism that generates kappa distributions involves a single or a series of stochastic or physical processes that induces local correlations among particles. We identify three fundamental solar wind plasma conditions that can generate kappa distributions, noted as (i) Debye shielding, (ii) frozen IMF, and (iii) temperature fluctuations, each one prevailing in different scales of solar wind plasma and magnetic field properties. Moreover, our findings show that the kappa distributions, and thus, their generating mechanisms, vary significantly with solar wind features: (i) the kappa index has different dependence on the solar wind speed for slow and fast modes, i.e., slow wind is characterized by a quasi-constant kappa index, κ ≈ 4.3 ± 0.7, while fast wind exhibits kappa indices that increase with bulk speed; (ii) the dispersion of magnetosonic waves is more effective for lower kappa indices (i.e., further from thermal equilibrium); and (iii) the kappa and polytropic indices are positively correlated, as it was anticipated by the theory.

  15. PIC simulations of a three component plasma described by Kappa distribution functions as observed in Saturn's magnetosphere

    NASA Astrophysics Data System (ADS)

    Barbosa, Marcos; Alves, Maria Virginia; Simões Junior, Fernando

    2016-04-01

    In plasmas out of thermodynamic equilibrium the particle velocity distribution can be described by the so called Kappa distribution. These velocity distribution functions are a generalization of the Maxwellian distribution. Since 1960, Kappa velocity distributions were observed in several regions of interplanetary space and astrophysical plasmas. Using KEMPO1 particle simulation code, modified to introduce Kappa distribution functions as initial conditions for particle velocities, the normal modes of propagation were analyzed in a plasma containing two species of electrons with different temperatures and densities and ions as a third specie.This type of plasma is usually found in magnetospheres such as in Saturn. Numerical solutions for the dispersion relation for such a plasma predict the presence of an electron-acoustic mode, besides the Langmuir and ion-acoustic modes. In the presence of an ambient magnetic field, the perpendicular propagation (Bernstein mode) also changes, as compared to a Maxwellian plasma, due to the Kappa distribution function. Here results for simulations with and without external magnetic field are presented. The parameters for the initial conditions in the simulations were obtained from the Cassini spacecraft data. Simulation results are compared with numerical solutions of the dispersion relation obtained in the literature and they are in good agreement.

  16. Kappa and other nonequilibrium distributions from the Fokker-Planck equation and the relationship to Tsallis entropy.

    PubMed

    Shizgal, Bernie D

    2018-05-01

    This paper considers two nonequilibrium model systems described by linear Fokker-Planck equations for the time-dependent velocity distribution functions that yield steady state Kappa distributions for specific system parameters. The first system describes the time evolution of a charged test particle in a constant temperature heat bath of a second charged particle. The time dependence of the distribution function of the test particle is given by a Fokker-Planck equation with drift and diffusion coefficients for Coulomb collisions as well as a diffusion coefficient for wave-particle interactions. A second system involves the Fokker-Planck equation for electrons dilutely dispersed in a constant temperature heat bath of atoms or ions and subject to an external time-independent uniform electric field. The momentum transfer cross section for collisions between the two components is assumed to be a power law in reduced speed. The time-dependent Fokker-Planck equations for both model systems are solved with a numerical finite difference method and the approach to equilibrium is rationalized with the Kullback-Leibler relative entropy. For particular choices of the system parameters for both models, the steady distribution is found to be a Kappa distribution. Kappa distributions were introduced as an empirical fitting function that well describe the nonequilibrium features of the distribution functions of electrons and ions in space science as measured by satellite instruments. The calculation of the Kappa distribution from the Fokker-Planck equations provides a direct physically based dynamical approach in contrast to the nonextensive entropy formalism by Tsallis [J. Stat. Phys. 53, 479 (1988)JSTPBS0022-471510.1007/BF01016429].

  17. Kappa and other nonequilibrium distributions from the Fokker-Planck equation and the relationship to Tsallis entropy

    NASA Astrophysics Data System (ADS)

    Shizgal, Bernie D.

    2018-05-01

    This paper considers two nonequilibrium model systems described by linear Fokker-Planck equations for the time-dependent velocity distribution functions that yield steady state Kappa distributions for specific system parameters. The first system describes the time evolution of a charged test particle in a constant temperature heat bath of a second charged particle. The time dependence of the distribution function of the test particle is given by a Fokker-Planck equation with drift and diffusion coefficients for Coulomb collisions as well as a diffusion coefficient for wave-particle interactions. A second system involves the Fokker-Planck equation for electrons dilutely dispersed in a constant temperature heat bath of atoms or ions and subject to an external time-independent uniform electric field. The momentum transfer cross section for collisions between the two components is assumed to be a power law in reduced speed. The time-dependent Fokker-Planck equations for both model systems are solved with a numerical finite difference method and the approach to equilibrium is rationalized with the Kullback-Leibler relative entropy. For particular choices of the system parameters for both models, the steady distribution is found to be a Kappa distribution. Kappa distributions were introduced as an empirical fitting function that well describe the nonequilibrium features of the distribution functions of electrons and ions in space science as measured by satellite instruments. The calculation of the Kappa distribution from the Fokker-Planck equations provides a direct physically based dynamical approach in contrast to the nonextensive entropy formalism by Tsallis [J. Stat. Phys. 53, 479 (1988), 10.1007/BF01016429].

  18. Ion firehose instability in a dusty plasma considering product-bi-kappa distributions for the plasma particles

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Santos, M. S. dos, E-mail: michel.santos@iffarroupilha.edu.br; Instituto Federal de Educação, Ciência e Tecnologia Farroupilha, 98590-000, Santo Augusto, RS; Ziebell, L. F., E-mail: luiz.ziebell@ufrgs.br

    2016-01-15

    We study the dispersion relation for low frequency waves in the whistler mode propagating along the ambient magnetic field, considering ions and electrons with product-bi-kappa (PBK) velocity distributions and taking into account the presence of a population of dust particles. The results obtained by numerical analysis of the dispersion relation show that the decrease in the κ indexes in the ion PBK distribution contributes to the increase in magnitude of the growth rates of the ion firehose instability and the size of the region in wave number space where the instability occurs. It is also shown that the decrease inmore » the κ indexes in the electron PBK distribution contribute to decrease in the growth rates of instability, despite the fact that the instability occurs due to the anisotropy in the ion distribution function. For most of the interval of κ values which has been investigated, the ability of the non-thermal ions to increase the instability overcomes the tendency of decrease due to the non-thermal electron distribution, but for very small values of the kappa indexes the deleterious effect of the non-thermal electrons tends to overcome the effect due to the non-thermal ion distribution.« less

  19. Particle-in-cell Simulations of Waves in a Plasma Described by Kappa Velocity Distribution as Observed in the Saturńs Magnetosphere

    NASA Astrophysics Data System (ADS)

    Alves, M. V.; Barbosa, M. V. G.; Simoes, F. J. L., Jr.

    2016-12-01

    Observations have shown that several regions in space plasmas exhibit non-Maxwellian distributions with high energy superthermal tails. Kappa velocity distribution functions can describe many of these regions and have been used since the 60's. They suit well to represent superthermal tails in solar wind as well as to obtain plasma parameters of plasma within planetary magnetospheres. A set of initial velocities following kappa distribution functions is used in KEMPO1 particle simulation code to analyze the normal modes of wave propagation. Initial conditions are determined using observed characteristics for Saturńs magnetosphere. Two electron species with different temperatures and densities and ions as a third species are used. Each electron population is described by a different kappa index. Particular attention is given to perpendicular propagation, Bernstein modes, and parallel propagation, Langmuir and electron-acoustic modes. The dispersion relation for the Bernstein modes is strongly influenced by the shape of the velocity distribution and consequently by the value of kappa index. Simulation results are compared with numerical solutions of the dispersion relation obtained in the literature and they are in good agreement.

  20. Self-consistent formation of electron $\\kappa$ distribution: 1. Theory

    NASA Astrophysics Data System (ADS)

    Yoon, Peter H.; Rhee, Tongnyeol; Ryu, Chang-Mo

    2006-09-01

    Since the early days of plasma physics research suprathermal electrons were observed to be generated during beam-plasma laboratory experiments. Energetic electrons, often modeled by κ distributions, are also ubiquitously observed in space. Various particle acceleration mechanisms have been proposed to explain such a feature, but all previous theories rely on either qualitative analytical method or on non-self-consistent approaches. This paper discusses the self-consistent acceleration of electrons to suprathermal energies by weak turbulence processes which involve the Langmuir/ion-sound turbulence and the beam-plasma interaction. It is discussed that the spontaneous scatttering process, which is absent in the purely collisionless theory, is singularly responsible for the generation of κ distributions. The conclusion is that purely collisionless Vlasov theory cannot produce suprathermal population.

  1. Plasma Dispersion Function for the Kappa Distribution

    NASA Technical Reports Server (NTRS)

    Podesta, John J.

    2004-01-01

    The plasma dispersion function is computed for a homogeneous isotropic plasma in which the particle velocities are distributed according to a Kappa distribution. An ordinary differential equation is derived for the plasma dispersion function and it is shown that the solution can be written in terms of Gauss' hypergeometric function. Using the extensive theory of the hypergeometric function, various mathematical properties of the plasma dispersion function are derived including symmetry relations, series expansions, integral representations, and closed form expressions for integer and half-integer values of K.

  2. Solitary Potential in a Space Plasma Containing Dynamical Heavy Ions and Bi-Kappa Distributed Electrons of Two Distinct Temperatures

    NASA Astrophysics Data System (ADS)

    Sarker, M.; Hosen, B.; Hossen, M. R.; Mamun, A. A.

    2018-01-01

    The heavy ion-acoustic solitary waves (HIASWs) in a magnetized, collisionless, space plasma system (containing dynamical heavy ions and bi-kappa distributed electrons of two distinct temperatures) have been theoretically investigated. The Korteweg-de Vries (K-dV), modified K-dV (MK-dV), and higher-order MK-dV (HMK-dV) equations are derived by employing the reductive perturbation method. The basic features of HIASWs (viz. speed, polarity, amplitude, width, etc.) are found to be significantly modified by the effects of number density and temperature of different plasma species, and external magnetic field (obliqueness). The K-dV and HM-KdV equations give rise to both compressive and rarefactive solitary structures, whereas the MK-dV equation supports only the compressive solitary structures. The implication of our results in some space and laboratory plasma situations are briefly discussed.

  3. Characteristic study of head-on collision of dust-ion acoustic solitons of opposite polarity with kappa distributed electrons

    NASA Astrophysics Data System (ADS)

    Parveen, Shahida; Mahmood, Shahzad; Adnan, Muhammad; Qamar, Anisa

    2016-09-01

    The head on collision between two dust ion acoustic (DIA) solitary waves, propagating in opposite directions, is studied in an unmagnetized plasma constituting adiabatic ions, static dust charged (positively/negatively) grains, and non-inertial kappa distributed electrons. In the linear limit, the dispersion relation of the dust ion acoustic (DIA) solitary wave is obtained using the Fourier analysis. For studying characteristic head-on collision of DIA solitons, the extended Poincaré-Lighthill-Kuo method is employed to obtain Korteweg-de Vries (KdV) equations with quadratic nonlinearities and investigated the phase shifts in their trajectories after the interaction. It is revealed that only compressive solitary waves can exist for the positive dust charged concentrations while for negative dust charge concentrations both the compressive and rarefactive solitons can propagate in such dusty plasma. It is found that for specific sets of plasma parameters, the coefficient of nonlinearity disappears in the KdV equation for the negative dust charged grains. Therefore, the modified Korteweg-de Vries (mKdV) equations with cubic nonlinearity coefficient, and their corresponding phase shift and trajectories, are also derived for negative dust charged grains plasma at critical composition. The effects of different plasma parameters such as superthermality, concentration of positively/negatively static dust charged grains, and ion to electron temperature ratio on the colliding soliton profiles and their corresponding phase shifts are parametrically examined.

  4. Estimations of Kappa parameter using quasi-thermal noise spectroscopy: Applications on Wind spacecraft

    NASA Astrophysics Data System (ADS)

    Martinović, M.

    2017-12-01

    Quasi-thermal noise (QTN) spectroscopy is an accurate technique for in situ measurements of electron density and temperature in space plasmas. The QTN spectrum has a characteristic noise peak just above the plasma frequency produced by electron quasi-thermal fluctuations, which allows a very accurate measurement of the electron density. The size and shape of the peak are determined by suprathermal electrons. Since this nonthermal electron population is well described by a generalized Lorentzian - Kappa velocity distribution, it is possible to determinate the distribution properties in the solar wind from a measured spectrum. In this work, we discuss some basic properties of the QTN spectrum dependence of the Kappa distribution parameters - total electron density, temperature and the Kappa index, giving an overview on how instrument characteristics and environment conditions affect quality of the measurements. Further on, we aim to apply the method to Wind Thermal Noise Receiver (TNR) measurements. However, the spectra observed by this instrument usually contain contributions from nonthermal phenomena, like ion acoustic waves below, or galactic noise above the plasma frequency. This is why, besides comparison of the theory with observations, work with Wind data requires development of a sophisticated algorithm that distinguish parts of the spectra that are dominated by the QTN, and therefore can be used in our study. Postulates of this algorithm, as well as major results of its implementation, are also presented.

  5. Kinetic Features Observed in the Solar Wind Electron Distributions

    NASA Astrophysics Data System (ADS)

    Pierrard, V.; Lazar, M.; Poedts, S.

    2016-12-01

    More than 120 000 of velocity distributions measured by Helios, Cluster and Ulysses in the ecliptic have been analyzed within an extended range of heliocentric distances from 0.3 to over 4 AU. The velocity distribution of electrons reveal a dual structure with a thermal (Maxwellian) core and a suprathermal (Kappa) halo. A detailed observational analysis of these two components provides estimations of their temperatures and temperature anisotropies, and we decode any potential interdependence that their properties may indicate. The core temperature is found to decrease with the radial distance, while the halo temperature slightly increases, clarifying an apparent contradiction in previous observational analysis and providing valuable clues about the temperature of the Kappa-distributed populations. For low values of the power-index kappa, these two components manifest a clear tendency to deviate from isotropy in the same direction, that seems to confirm the existence of mechanisms with similar effects on both components, e.g., the solar wind expansion, or the particle heating by the fluctuations. However, the existence of plasma states with anti-correlated anisotropies of the core and halo populations and the increase of their number for high values of the power-index kappa suggest a dynamic interplay of these components, mediated most probably by the anisotropy-driven instabilities. Estimating the temperature of the solar wind particles and their anisotropies is particularly important for understanding the origin of these deviations from thermal equilibrium as well as their effects.

  6. On the equilibrium between proton kappa distribution and compressible kinetic Alfvenic fluctuations

    NASA Astrophysics Data System (ADS)

    Yoon, P. H.

    2017-12-01

    Protons with a quasi inverse power law energetic population featuring the property f v-α, with α close to 5, are pervasively observed in the heliosphere. While many theoretical attempts have been made in order to describe such a feature, the so-called pump acceleration mechanism put forth by Fisk & Gloeckler is one of the most prominent theories. Their mechanism involves the low-frequency compressional fluctuations accelerating the protons. This presentation aims to reformulate the problem from the perspective of the steady state solution of the self-consistent plasma kinetic theory involving compressible kinetic Alfvenic fluctuations. By considering the steady state proton particle kinetic equation and quasi-linear wave kinetic for the kinetic Alfvenic turbulence we seek to obtain concomitant solutions for both proton velocity distribution function and the spectral intensity for kinetic Alfvenic fluctuation. It is found that the kappa distribution for the protons is a legitimate, if not unique, solution. The steady state spectrum of kinetic Alfvenic fluctuation is also obtained. The present investigation demonstrates that the kappa distribution for the protons featuring energetic tail population characterized by f v-2κ-2, where κ is the parameter for kappa distribution, may represent the background population of the protons in the heliosphere. However, it is speculated that in order to uniquely determine the value of κ, which must be close to 1.5 for asymptotic behavior of f v-5, one must have an additional constraint that involves the balance of nonlinear mode coupling terms in the wave kinetic equation.

  7. Oblique propagation of solitary waves in weakly relativistic magnetized plasma with kappa distributed electrons in the presence of negative ions

    NASA Astrophysics Data System (ADS)

    Salmanpoor, H.; Sharifian, M.; Gholipour, S.; Borhani Zarandi, M.; Shokri, B.

    2018-03-01

    The oblique propagation of nonlinear ion acoustic solitary waves (solitons) in magnetized collisionless and weakly relativistic plasma with positive and negative ions and super thermal electrons has been examined by using reduced perturbation method to obtain the Korteweg-de Vries equation that admits an obliquely propagating soliton solution. We have investigated the effects of plasma parameters like negative ion density, electrons temperature, angle between wave vector and magnetic field, ions velocity, and k (spectral index in kappa distribution) on the amplitude and width of solitary waves. It has been found out that four modes exist in our plasma model, but the analysis of the results showed that only two types of ion acoustic modes (fast and slow) exist in the plasma and in special cases only one mode could be propagated. The parameters of plasma for these two modes (or one mode) determine which one is rarefactive and which one is compressive. The main parameter is negative ions density (β) indicating which mode is compressive or rarefactive. The effects of the other plasma parameters on amplitude and width of the ion acoustic solitary waves have been studied. The main conclusion is that the effects of the plasma parameters on amplitude and width of the solitary wave strongly depend on the value of the negative ion density.

  8. Kappa Distribution in a Homogeneous Medium: Adiabatic Limit of a Super-diffusive Process?

    NASA Astrophysics Data System (ADS)

    Roth, I.

    2015-12-01

    The classical statistical theory predicts that an ergodic, weakly interacting system like charged particles in the presence of electromagnetic fields, performing Brownian motions (characterized by small range deviations in phase space and short-term microscopic memory), converges into the Gibbs-Boltzmann statistics. Observation of distributions with a kappa-power-law tails in homogeneous systems contradicts this prediction and necessitates a renewed analysis of the basic axioms of the diffusion process: characteristics of the transition probability density function (pdf) for a single interaction, with a possibility of non-Markovian process and non-local interaction. The non-local, Levy walk deviation is related to the non-extensive statistical framework. Particles bouncing along (solar) magnetic field with evolving pitch angles, phases and velocities, as they interact resonantly with waves, undergo energy changes at undetermined time intervals, satisfying these postulates. The dynamic evolution of a general continuous time random walk is determined by pdf of jumps and waiting times resulting in a fractional Fokker-Planck equation with non-integer derivatives whose solution is given by a Fox H-function. The resulting procedure involves the known, although not frequently used in physics fractional calculus, while the local, Markovian process recasts the evolution into the standard Fokker-Planck equation. Solution of the fractional Fokker-Planck equation with the help of Mellin transform and evaluation of its residues at the poles of its Gamma functions results in a slowly converging sum with power laws. It is suggested that these tails form the Kappa function. Gradual vs impulsive solar electron distributions serve as prototypes of this description.

  9. Korteweg-deVries-Burgers (KdVB) equation in a five component cometary plasma with kappa described electrons and ions

    NASA Astrophysics Data System (ADS)

    Michael, Manesh; Willington, Neethu T.; Jayakumar, Neethu; Sebastian, Sijo; Sreekala, G.; Venugopal, Chandu

    2016-12-01

    We investigate the existence of ion-acoustic shock waves in a five component cometary plasma consisting of positively and negatively charged oxygen ions, kappa described hydrogen ions, hot solar electrons, and slightly colder cometary electrons. The KdVB equation has been derived for the system, and its solution plotted for different kappa values, oxygen ion densities, as well as the temperature ratios for the ions. It is found that the amplitude of the shock wave decreases with increasing kappa values. The strength of the shock profile decreases with increasing temperatures of the positively charged oxygen ions and densities of negatively charged oxygen ions.

  10. Marginal instability threshold of magnetosonic waves in kappa distributed plasma

    NASA Astrophysics Data System (ADS)

    Bashir, M. F.; Manzoor, M. Z.; Ilie, R.; Yoon, P. H.; Miasli, M. S.

    2017-12-01

    The dispersion relation of magnetosonic wave is studied taking the non-extensive anisotropic counter-streaming distribution which follows the Tsallis statistics. The effects of non-extensivity parameter (q), counter-streaming parameter (P) and the wave-particle interaction is analyzed on the growth rate and the marginal instability threshold condition of Magnetosonic (MS) mode to provide the possible explanation of different regions the Bale-diagram obtained from the solar wind data at 1 AU as represented by the temperature anisotropy ( ) vs plasma beta ( ) solar wind data plot. It is shown that the most of the regions of Bale-diagram is bounded by the MS instability under different condition and best fitted by the non-extesnive distribution. The results for the bi-kappa distribution and bi- Maxwellian distribution are also obtained in the limits and respectively.

  11. Phenotyping polyclonal kappa and lambda light chain molecular mass distributions in patient serum using mass spectrometry.

    PubMed

    Barnidge, David R; Dasari, Surendra; Ramirez-Alvarado, Marina; Fontan, Adrian; Willrich, Maria A V; Tschumper, Renee C; Jelinek, Diane F; Snyder, Melissa R; Dispenzieri, Angela; Katzmann, Jerry A; Murray, David L

    2014-11-07

    We previously described a microLC-ESI-Q-TOF MS method for identifying monoclonal immunoglobulins in serum and then tracking them over time using their accurate molecular mass. Here we demonstrate how the same methodology can be used to identify and characterize polyclonal immunoglobulins in serum. We establish that two molecular mass distributions observed by microLC-ESI-Q-TOF MS are from polyclonal kappa and lambda light chains using a combination of theoretical molecular masses from gene sequence data and the analysis of commercially available purified polyclonal IgG kappa and IgG lambda from normal human serum. A linear regression comparison of kappa/lambda ratios for 74 serum samples (25 hypergammaglobulinemia, 24 hypogammaglobulinemia, 25 normal) determined by microflowLC-ESI-Q-TOF MS and immunonephelometry had a slope of 1.37 and a correlation coefficient of 0.639. In addition to providing kappa/lambda ratios, the same microLC-ESI-Q-TOF MS analysis can determine the molecular mass for oligoclonal light chains observed above the polyclonal background in patient samples. In 2 patients with immune disorders and hypergammaglobulinemia, we observed a skewed polyclonal molecular mass distribution which translated into biased kappa/lambda ratios. Mass spectrometry provides a rapid and simple way to combine the polyclonal kappa/lambda light chain abundance ratios with the identification of dominant monoclonal as well as oligoclonal light chain immunoglobulins. We anticipate that this approach to evaluating immunoglobulin light chains will lead to improved understanding of immune deficiencies, autoimmune diseases, and antibody responses.

  12. Whistler waves with electron temperature anisotropy and non-Maxwellian distribution functions

    NASA Astrophysics Data System (ADS)

    Malik, M. Usman; Masood, W.; Qureshi, M. N. S.; Mirza, Arshad M.

    2018-05-01

    The previous works on whistler waves with electron temperature anisotropy narrated the dependence on plasma parameters, however, they did not explore the reasons behind the observed differences. A comparative analysis of the whistler waves with different electron distributions has not been made to date. This paper attempts to address both these issues in detail by making a detailed comparison of the dispersion relations and growth rates of whistler waves with electron temperature anisotropy for Maxwellian, Cairns, kappa and generalized (r, q) distributions by varying the key plasma parameters for the problem under consideration. It has been found that the growth rate of whistler instability is maximum for flat-topped distribution whereas it is minimum for the Maxwellian distribution. This work not only summarizes and complements the previous work done on the whistler waves with electron temperature anisotropy but also provides a general framework to understand the linear propagation of whistler waves with electron temperature anisotropy that is applicable in all regions of space plasmas where the satellite missions have indicated their presence.

  13. Low frequency electromagnetic fluctuations in Kappa magnetized plasmas

    NASA Astrophysics Data System (ADS)

    Kim, Sunjung; Lazar, M.; Schlickeiser, R.; López, R. A.; Yoon, P. H.

    2018-07-01

    The present paper provides a theoretical approach for the evaluation of the low frequency spontaneously emitted electromagnetic (EM) fluctuations in Kappa magnetized plasmas, which include the kinetic Alfvén, fast magnetosonic/whistler, kinetic slow mode, ion Bernstein cyclotron modes, and higher-order modes. The model predictions are consistent with particle-in-cell simulations. Effects of suprathermal particles on low frequency fluctuations are studied by varying the power index, either for ions (κ i) or for electrons (κ e). Computations for an arbitrary wave vector orientation and wave polarization provide the intensity of spontaneous emissions to be enhanced in the presence of suprathermal populations. These results strongly suggest that spontaneous fluctuations may significantly contribute to the EM fluctuations observed in space plasmas, where suprathermal Kappa distributed particles are ubiquitous.

  14. Characterization of kappa 1 and kappa 2 opioid binding sites in frog (Rana esculenta) brain membrane preparation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Benyhe, S.; Varga, E.; Hepp, J.

    1990-09-01

    The distribution and properties of frog brain kappa-opioid receptor subtypes differ not only from those of the guinea pig brain, but also from that of the rat brain. In guinea pig cerebellum the kappa 1 is the dominant receptor subtype, frog brain contains mainly the kappa 2 subtype, and the distribution of the rat brain subtypes is intermediate between the two others. In competition experiments it has been established that ethylketocyclazocine and N-cyclopropylmethyl-norazidomorphine, which are nonselective kappa-ligands, have relatively high affinities to frog brain membranes. The kappa 2 ligands (Met5)enkephalin-Arg6-Phe7 and etorphine also show high affinities to the frog brain.more » Kappa 1 binding sites measured in the presence of 5 microM/D-Ala2-Leu5/enkephalin represent 25-30% of (3H)ethylketocyclazocine binding in frog brain membranes. The kappa 2 subtype in frog brain resembles more to the mu subtype than the delta subtype of opioid receptors, but it differs from the mu subtype in displaying low affinity toward beta-endorphin and /D-Ala2-(Me)Phe4-Gly5-ol/enkephalin (DAGO). From our data it is evident that the opioid receptor subtypes are already present in the amphibian brain but the differences among them are less pronounced than in mammalian brain.« less

  15. The disagreeable behaviour of the kappa statistic.

    PubMed

    Flight, Laura; Julious, Steven A

    2015-01-01

    It is often of interest to measure the agreement between a number of raters when an outcome is nominal or ordinal. The kappa statistic is used as a measure of agreement. The statistic is highly sensitive to the distribution of the marginal totals and can produce unreliable results. Other statistics such as the proportion of concordance, maximum attainable kappa and prevalence and bias adjusted kappa should be considered to indicate how well the kappa statistic represents agreement in the data. Each kappa should be considered and interpreted based on the context of the data being analysed. Copyright © 2014 John Wiley & Sons, Ltd.

  16. Preliminary Estimation of Kappa Parameter in Croatia

    NASA Astrophysics Data System (ADS)

    Stanko, Davor; Markušić, Snježana; Ivančić, Ines; Mario, Gazdek; Gülerce, Zeynep

    2017-12-01

    Spectral parameter kappa κ is used to describe spectral amplitude decay “crash syndrome” at high frequencies. The purpose of this research is to estimate spectral parameter kappa for the first time in Croatia based on small and moderate earthquakes. Recordings of local earthquakes with magnitudes higher than 3, epicentre distances less than 150 km, and focal depths less than 30 km from seismological stations in Croatia are used. The value of kappa was estimated from the acceleration amplitude spectrum of shear waves from the slope of the high-frequency part where the spectrum starts to decay rapidly to a noise floor. Kappa models as a function of a site and distance were derived from a standard linear regression of kappa-distance dependence. Site kappa was determined from the extrapolation of the regression line to a zero distance. The preliminary results of site kappa across Croatia are promising. In this research, these results are compared with local site condition parameters for each station, e.g. shear wave velocity in the upper 30 m from geophysical measurements and with existing global shear wave velocity - site kappa values. Spatial distribution of individual kappa’s is compared with the azimuthal distribution of earthquake epicentres. These results are significant for a couple of reasons: to extend the knowledge of the attenuation of near-surface crust layers of the Dinarides and to provide additional information on the local earthquake parameters for updating seismic hazard maps of studied area. Site kappa can be used in the re-creation, and re-calibration of attenuation of peak horizontal and/or vertical acceleration in the Dinarides area since information on the local site conditions were not included in the previous studies.

  17. Non-equilibrium thermionic electron emission for metals at high temperatures

    NASA Astrophysics Data System (ADS)

    Domenech-Garret, J. L.; Tierno, S. P.; Conde, L.

    2015-08-01

    Stationary thermionic electron emission currents from heated metals are compared against an analytical expression derived using a non-equilibrium quantum kappa energy distribution for the electrons. The latter depends on the temperature decreasing parameter κ ( T ) , which decreases with increasing temperature and can be estimated from raw experimental data and characterizes the departure of the electron energy spectrum from equilibrium Fermi-Dirac statistics. The calculations accurately predict the measured thermionic emission currents for both high and moderate temperature ranges. The Richardson-Dushman law governs electron emission for large values of kappa or equivalently, moderate metal temperatures. The high energy tail in the electron energy distribution function that develops at higher temperatures or lower kappa values increases the emission currents well over the predictions of the classical expression. This also permits the quantitative estimation of the departure of the metal electrons from the equilibrium Fermi-Dirac statistics.

  18. The electron distribution function downstream of the solar-wind termination shock: Where are the hot electrons?

    NASA Astrophysics Data System (ADS)

    Fahr, Hans J.; Richardson, John D.; Verscharen, Daniel

    2015-07-01

    In the majority of the literature on plasma shock waves, electrons play the role of "ghost particles", since their contribution to mass and momentum flows is negligible, and they have been treated as only taking care of the electric plasma neutrality. In some more recent papers, however, electrons play a new important role in the shock dynamics and thermodynamics, especially at the solar-wind termination shock. They react on the shock electric field in a very specific way, leading to suprathermal nonequilibrium distributions of the downstream electrons, which can be represented by a kappa distribution function. In this paper, we discuss why this anticipated hot electron population has not been seen by the plasma detectors of the Voyager spacecraft downstream of the solar-wind termination shock. We show that hot nonequilibrium electrons induce a strong negative electric charge-up of any spacecraft cruising through this downstream plasma environment. This charge reduces electron fluxes at the spacecraft detectors to nondetectable intensities. Furthermore, we show that the Debye length λDκ grows to values of about λDκ/λD ≃ 106 compared to the classical value λD in this hot-electron environment. This unusual condition allows for the propagation of a certain type of electrostatic plasma waves that, at very large wavelengths, allow us to determine the effective temperature of the suprathermal electrons directly by means of the phase velocity of these waves. At moderate wavelengths, the electron-acoustic dispersion relation leads to nonpropagating oscillations with the ion-plasma frequency ωp, instead of the traditional electron plasma frequency.

  19. Obliquely Propagating Waves in Bi-Kappa Plasmas

    NASA Astrophysics Data System (ADS)

    Gaelzer, R.; Ziebell, L. F.; Meneses, A. R.

    2016-12-01

    The effects of kappa velocity distribution functions (VDFs) have been the subjectof intense research. Such functions have beenfound to provide a better fitting to the VDFs measured by spacecraftin the solar wind. An anisotropic VDF contains free energy that can excite wavesin the plasma. The induced turbulence also determines the observed shape of the VDF.The general treatment for waves excited by (bi-)Maxwellian plasmas is well-established.However, for kappa distributions (isotropic or anisotropic), the majority of the studieswere restricted to the limiting cases of purely parallel or perpendicular propagation.Contributions to the general case of obliquely-propagating waves have been scarcely reported.The absence of a general treatment prevents a complete analysis of the wave-particle interactionin kappa plasmas, since some instabilities can operate both in the parallel and oblique directions.A series of papers published by the authors begin to remedy this situation. In a first work [1],we have obtained the dielectric tensor and dispersion relations for quasi-perpendicular dispersive Alfvén waves resulting from a kappa VDF. This approach was later generalized by [2],where the formalism was extended to the general case of electrostatic/electromagnetic waves propagatingin an isotropic kappa plasma in any frequency range and for arbitrary angles.In the present work [3], we generalize even further the formalism by the derivation of thegeneral dielectric tensor of an anisotropic bi-kappa plasma. We present the state-of-the-art of theformalism and show how it enables a systematic study of waves and instabilities propagating inarbitrary directions and frequencies in a bi-kappa plasma.[1] R. Gaelzer, L. F. Ziebell, J. Geophys. Res. 119, 9334 (2014), doi: 10.1002/2014JA020667.[2] R. Gaelzer, L. F. Ziebell, Phys. Plasmas 23, 022110 (2016), doi: 10.1063/1.4941260.[3] R. Gaelzer et al., Phys. Plasmas 23, 062108 (2016), doi: 10.1063/1.4953430.

  20. Determining plasma parameters in cold, multi-species plasmas using Maxwell and Kappa distribution functions.

    NASA Astrophysics Data System (ADS)

    Jahn, J. M.; Denton, R. E.; Nose, M.; Bonnell, J. W.; Kurth, W. S.; Livadiotis, G.; Larsen, B.; Goldstein, J.

    2016-12-01

    Determining the total plasma density from ion data is essentially an impossible task for particle instruments. The lowest instrument energy threshold never includes the coldest particles (i.e., Emin> 0 eV), and any positive spacecraft charging—which is normal for a sunlit spacecraft—exacerbates the problem by shifting the detectable minimum energy to higher values. For ion data, traditionally field line resonance measurements of ULF waves in the magnetosphere have been used to determine the mass loading of magnetic field lines in this case. This approach delivers a reduced ion mass M that represents the mass ratio of all ions on a magnetic field line. For multi-species plasmas like the plasmasphere this bounds the problem, but it does not provide a unique solution. To at least estimate partial densities using particle instruments, one traditionally performs fits to the measured particle distribution functions under the assumption that the underlying particle distributions are Maxwellian. Uncertainties performing a fit aside, there is usually no possibility to detect a possible bi-Maxwellian distribution where one of the Maxwellians is very cold. The tail of such a distribution may fall completely below the low energy threshold of the measurement. In this paper we present a different approach to determining the fractional temperatures Ti and densities ni in a multi-species plasma. First, we describe and demonstrate an approach to determine Ti and ni that does not require fitting but relies more on the mathematical properties of the distribution functions. We apply our approach to Van Allen Probes measurements of the plasmaspheric H+, He+, and O+ distribution functions under the assumption that the particle distributions are Maxwellian. We compare our results to mass loading results from the Van Allen Probes field line resonance analyses (for composition) and to the total (electron) plasma density derived from the EFW and EMFISIS experiments. Then we expand our

  1. Count on kappa.

    PubMed

    Czodrowski, Paul

    2014-11-01

    In the 1960s, the kappa statistic was introduced for the estimation of chance agreement in inter- and intra-rater reliability studies. The kappa statistic was strongly pushed by the medical field where it could be successfully applied via analyzing diagnoses of identical patient groups. Kappa is well suited for classification tasks where ranking is not considered. The main advantage of kappa is its simplicity and the general applicability to multi-class problems which is the major difference to receiver operating characteristic area under the curve. In this manuscript, I will outline the usage of kappa for classification tasks, and I will evaluate the role and uses of kappa in specifically machine learning and cheminformatics.

  2. Porcine arterivirus activates the NF-{kappa}B pathway through I{kappa}B degradation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lee, Sang-Myeong; Kleiboeker, Steven B.

    2005-11-10

    Nuclear factor-kappaB (NF-{kappa}B) is a critical regulator of innate and adaptive immune function as well as cell proliferation and survival. The present study demonstrated for the first time that a virus belonging to the Arteriviridae family activates NF-{kappa}B in MARC-145 cells and alveolar macrophages. In porcine reproductive and respiratory syndrome virus (PRRSV)-infected cells, NF-{kappa}B activation was characterized by translocation of NF-{kappa}B from the cytoplasm to the nucleus, increased DNA binding activity, and NF-{kappa}B-regulated gene expression. NF-{kappa}B activation was increased as PRRSV infection progressed and in a viral dose-dependent manner. UV-inactivation of PRRSV significantly reduced the level of NF-{kappa}B activation. Degradationmore » of I{kappa}B protein was detected late in PRRSV infection, and overexpression of the dominant negative form of I{kappa}B{alpha} (I{kappa}B{alpha}DN) significantly suppressed NF-{kappa}B activation induced by PRRSV. However, I{kappa}B{alpha}DN did not affect viral replication and viral cytopathic effect. PRRSV infection induced oxidative stress in cells by generating reactive oxygen species (ROS), and antioxidants inhibited NF-{kappa}B DNA binding activity in PRRSV-infected cells, suggesting ROS as a mechanism by which NF-{kappa}B was activated by PRRSV infection. Moreover, NF-{kappa}B-dependent expression of matrix metalloproteinase (MMP)-2 and MMP-9 was observed in PRRSV-infected cells, an observation which implies that NF-{kappa}B activation is a biologically significant aspect of PRRSV pathogenesis. The results presented here provide a basis for understanding molecular pathways of pathology and immune evasion associated with disease caused by PRRSV.« less

  3. Bernstein-Greene-Kruskal theory of electron holes in superthermal space plasma

    NASA Astrophysics Data System (ADS)

    Aravindakshan, Harikrishnan; Kakad, Amar; Kakad, Bharati

    2018-05-01

    Several spacecraft missions have observed electron holes (EHs) in Earth's and other planetary magnetospheres. These EHs are modeled with the stationary solutions of Vlasov-Poisson equations, obtained by adopting the Bernstein-Greene-Kruskal (BGK) approach. Through the literature survey, we find that the BGK EHs are modelled by using either thermal distribution function or any statistical distribution derived from particular spacecraft observations. However, Maxwell distributions are quite rare in space plasmas; instead, most of these plasmas are superthermal in nature and generally described by kappa distribution. We have developed a one-dimensional BGK model of EHs for space plasma that follows superthermal kappa distribution. The analytical solution of trapped electron distribution function for such plasmas is derived. The trapped particle distribution function in plasma following kappa distribution is found to be steeper and denser as compared to that for Maxwellian distribution. The width-amplitude relation of perturbation for superthermal plasma is derived and allowed regions of stable BGK solutions are obtained. We find that the stable BGK solutions are better supported by superthermal plasmas compared to that of thermal plasmas for small amplitude perturbations.

  4. Pharmacological characterization of the cloned kappa opioid receptor as a kappa 1b subtype.

    PubMed

    Lai, J; Ma, S W; Zhu, R H; Rothman, R B; Lentes, K U; Porreca, F

    1994-10-27

    Substantial pharmacological evidence in vitro and in vivo has suggested the existence of subtypes of the kappa opioid receptor. Quantitative radioligand binding techniques resolved the presence of two high affinity binding sites for the kappa 1 ligand [3H]U69,593 in mouse brain membranes, termed kappa 1a and kappa 1b, respectively. Whereas the kappa 1a site has high affinity for fedotozine and oxymorphindole and low affinity for bremazocine and alpha-neoendorphin, site kappa 1b has high affinity for bremazocine and alpha-neoendorphin and low affinity for fedotozine and oxymorphindole. CI-977 and U69,593 bind equally well at both sites. To determine the relationship between these kappa 1 receptor subtypes and the recently cloned mouse kappa 1 receptor (KOR), we examined [3H]U69,593 binding to the KOR in stably transfected cells (KORCHN-8). Competition of [3H]U69,593 binding to the KOR by bremazocine, alpha-neoendorphin, fedotozine and oxymorphindole resolved a single class of binding sites at which these agents had binding affinities similar to that of the kappa 1b site present in mouse brain. These results suggest that the cloned KOR corresponds to the kappa 1 site in mouse brain defined as kappa 1b.

  5. Kappa statistic for clustered matched-pair data.

    PubMed

    Yang, Zhao; Zhou, Ming

    2014-07-10

    Kappa statistic is widely used to assess the agreement between two procedures in the independent matched-pair data. For matched-pair data collected in clusters, on the basis of the delta method and sampling techniques, we propose a nonparametric variance estimator for the kappa statistic without within-cluster correlation structure or distributional assumptions. The results of an extensive Monte Carlo simulation study demonstrate that the proposed kappa statistic provides consistent estimation and the proposed variance estimator behaves reasonably well for at least a moderately large number of clusters (e.g., K ≥50). Compared with the variance estimator ignoring dependence within a cluster, the proposed variance estimator performs better in maintaining the nominal coverage probability when the intra-cluster correlation is fair (ρ ≥0.3), with more pronounced improvement when ρ is further increased. To illustrate the practical application of the proposed estimator, we analyze two real data examples of clustered matched-pair data. Copyright © 2014 John Wiley & Sons, Ltd.

  6. 40 CFR 721.10033 - Zinc, [ethanedioato(2-)-. kappa. O1, . kappa. O2]-.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Zinc, [ethanedioato(2-)-. kappa. O1... Specific Chemical Substances § 721.10033 Zinc, [ethanedioato(2-)-. kappa. O1, . kappa. O2]-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as zinc...

  7. 40 CFR 721.10033 - Zinc, [ethanedioato(2-)-. kappa. O1, . kappa. O2]-.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Zinc, [ethanedioato(2-)-. kappa. O1... Specific Chemical Substances § 721.10033 Zinc, [ethanedioato(2-)-. kappa. O1, . kappa. O2]-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as zinc...

  8. Wigner distributions for an electron

    NASA Astrophysics Data System (ADS)

    Kumar, Narinder; Mondal, Chandan

    2018-06-01

    We study the Wigner distributions for a physical electron, which reveal the multidimensional images of the electron. The physical electron is considered as a composite system of a bare electron and photon. The Wigner distributions for unpolarized, longitudinally polarized and transversely polarized electron are presented in transverse momentum plane as well as in impact-parameter plane. The spin-spin correlations between the bare electron and the physical electron are discussed. We also evaluate all the leading twist generalized transverse momentum distributions (GTMDs) for electron.

  9. KAPPA -- Kernel Application Package

    NASA Astrophysics Data System (ADS)

    Currie, Malcolm J.; Berry, David. S.

    KAPPA is an applications package comprising about 180 general-purpose commands for image processing, data visualisation, and manipulation of the standard Starlink data format---the NDF. It is intended to work in conjunction with Starlink's various specialised packages. In addition to the NDF, KAPPA can also process data in other formats by using the `on-the-fly' conversion scheme. Many commands can process data arrays of arbitrary dimension, and others work on both spectra and images. KAPPA operates from both the UNIX C-shell and the ICL command language. This document describes how to use KAPPA and its features. There is some description of techniques too, including a section on writing scripts. This document includes several tutorials and is illustrated with numerous examples. The bulk of this document comprises detailed descriptions of each command as well as classified and alphabetical summaries.

  10. Interrater reliability: the kappa statistic.

    PubMed

    McHugh, Mary L

    2012-01-01

    The kappa statistic is frequently used to test interrater reliability. The importance of rater reliability lies in the fact that it represents the extent to which the data collected in the study are correct representations of the variables measured. Measurement of the extent to which data collectors (raters) assign the same score to the same variable is called interrater reliability. While there have been a variety of methods to measure interrater reliability, traditionally it was measured as percent agreement, calculated as the number of agreement scores divided by the total number of scores. In 1960, Jacob Cohen critiqued use of percent agreement due to its inability to account for chance agreement. He introduced the Cohen's kappa, developed to account for the possibility that raters actually guess on at least some variables due to uncertainty. Like most correlation statistics, the kappa can range from -1 to +1. While the kappa is one of the most commonly used statistics to test interrater reliability, it has limitations. Judgments about what level of kappa should be acceptable for health research are questioned. Cohen's suggested interpretation may be too lenient for health related studies because it implies that a score as low as 0.41 might be acceptable. Kappa and percent agreement are compared, and levels for both kappa and percent agreement that should be demanded in healthcare studies are suggested.

  11. Existence regimes for the formation of nonlinear dissipative structures in inhomogeneous magnetoplasmas with non-Maxwellian electrons

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Masood, W.; National Centre for Physics, Shahdara Valley Road, Islamabad; Zahoor, Sara

    2016-09-15

    Nonlinear dissipative structures are studied in one and two dimensions in nonuniform magnetized plasmas with non-Maxwellian electrons. The dissipation is incorporated in the system through ion-neutral collisions. Employing the drift approximation, nonlinear drift waves are derived in 1D, whereas coupled drift-ion acoustic waves are derived in 2D in the weak nonlinearity limit. It is found that the ratio of the diamagnetic drift velocity to the velocity of nonlinear structure determines the nature (compressive or rarefactive) of the shock structure. The upper and lower bounds for velocity of the nonlinear shock structures are also found. It is noticed that the existencemore » regimes for the drift shock waves in one and two dimensions for Cairns distributed electrons are very distinct from those with kappa distributed electrons. Interestingly, it is found that both compressive and rarefactive shock structures could be obtained for the one dimensional drift waves with kappa distributed electrons.« less

  12. Existence regimes for the formation of nonlinear dissipative structures in inhomogeneous magnetoplasmas with non-Maxwellian electrons

    NASA Astrophysics Data System (ADS)

    Masood, W.; Zahoor, Sara; Gul-e-Ali, Ahmad, Ali

    2016-09-01

    Nonlinear dissipative structures are studied in one and two dimensions in nonuniform magnetized plasmas with non-Maxwellian electrons. The dissipation is incorporated in the system through ion-neutral collisions. Employing the drift approximation, nonlinear drift waves are derived in 1D, whereas coupled drift-ion acoustic waves are derived in 2D in the weak nonlinearity limit. It is found that the ratio of the diamagnetic drift velocity to the velocity of nonlinear structure determines the nature (compressive or rarefactive) of the shock structure. The upper and lower bounds for velocity of the nonlinear shock structures are also found. It is noticed that the existence regimes for the drift shock waves in one and two dimensions for Cairns distributed electrons are very distinct from those with kappa distributed electrons. Interestingly, it is found that both compressive and rarefactive shock structures could be obtained for the one dimensional drift waves with kappa distributed electrons.

  13. Cationization of kappa- and iota-carrageenan--Characterization and properties of amphoteric polysaccharides.

    PubMed

    Barahona, Tamara; Prado, Héctor J; Bonelli, Pablo R; Cukierman, Ana L; Fissore, Eliana L; Gerschenson, Lia N; Matulewicz, María C

    2015-08-01

    Commercial kappa- and iota carrageenans were cationized with 3-chloro-2-hydroxypropyltrimethylammonium chloride in aqueous sodium hydroxide solution. For kappa-carrageenan three derivatives with different degrees of substitution were obtained. Native and amphoteric kappa-carrageenans were characterized by NMR and infrared spectroscopy, scanning electron and atomic force microscopy; methanolysis products were studied by electrospray ionization mass spectrometry. Young moduli and the strain at break of films, differential scanning calorimetry, rheological and flocculation behavior were also evaluated; the native and the amphoteric derivatives showed different and interesting properties. Cationization of iota-carrageenan was more difficult, indicating as it was previously observed for agarose, that substitution starts preferentially on the 2-position of 3,6-anhydrogalactose residues; in iota-carrageenan this latter unit is sulfated. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Heat shock protein 70 negatively regulates the heat-shock-induced suppression of the I{kappa}B/NF-{kappa}B cascade by facilitating I{kappa}B kinase renaturation and blocking its further denaturation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lee, Kyoung-Hee; Lee, Choon-Taek; Kim, Young Whan

    2005-07-01

    Heat shock (HS) treatment has been previously shown to suppress the I{kappa}B/nuclear factor-{kappa}B (NF-{kappa}B) cascade by denaturing, and thus inactivating I{kappa}B kinase (IKK). HS is characterized by the induction of a group of heat shock proteins (HSPs). However, their role in the HS-induced suppression of the I{kappa}B/NF-{kappa}B cascade is unclear. Adenovirus-mediated HSP70 overexpression was found not to suppress the TNF-{alpha}-induced activation of the I{kappa}B/NF-{kappa}B pathway, thus suggesting that HSP70 is unlikely to suppress this pathway. When TNF-{alpha}-induced activation of the I{kappa}B/NF-{kappa}B pathway was regained 24 h after HS, HSP70 was found to be highly up-regulated. Moreover, blocking HSP70 induction delayedmore » TNF-{alpha}-induced I{kappa}B{alpha} degradation and the resolubilization of IKK. In addition, HSP70 associated physically with IKK, suggesting that HSP70 is involved in the recovery process via molecular chaperone effect. Adenovirus-mediated HSP70 overexpression prior to HS blocked the I{kappa}B{alpha} stabilizing effect of HS by suppressing IKK insolubilization. Moreover, the up-regulation of endogenous HSP70 by preheating, suppressed this subsequent HS-induced IKK insolubilization, and this effect was abrogated by blocking HSP70 induction. These findings indicate that HSP70 accumulates during HS and negatively regulates the HS-induced suppression of the I{kappa}B/NF-{kappa}B cascade by facilitating the renaturation of IKK and blocking its further denaturation.« less

  15. Effect of kappa distribution on the damping rate of the obliquely propagating magnetosonic mode

    NASA Astrophysics Data System (ADS)

    Imran, Ali KHAN; G, MURTAZA

    2018-03-01

    Data from spacecrafts suggest that space plasma has an abundance of suprathermal particles which are controlled by the spectral index κ when modeled on kappa particle velocity distribution. In this paper, considering homogeneous plasma, the effect of integer values of κ on the damping rate of an obliquely propagating magnetosonic (MS) wave is studied. The frequency of the MS wave is assumed to be less than ion cyclotron frequency, i.e., ω \\ll {ω }{{i}}. Under this assumption, the dispersion relation is investigated both numerically and analytically, and it is found that the real frequency of the wave is not a sensitive function of κ, but the imaginary part of the frequency is. It is also shown that for those values of κ where a large number of resonant particles participate in wave-particle interaction, the wave is heavily damped, as expected. The possible application of the results to the solar wind is discussed.

  16. Inequalities between Kappa and Kappa-Like Statistics for "k x k" Tables

    ERIC Educational Resources Information Center

    Warrens, Matthijs J.

    2010-01-01

    The paper presents inequalities between four descriptive statistics that can be expressed in the form [P-E(P)]/[1-E(P)], where P is the observed proportion of agreement of a "kappa x kappa" table with identical categories, and E(P) is a function of the marginal probabilities. Scott's "pi" is an upper bound of Goodman and Kruskal's "lambda" and a…

  17. 40 CFR 721.10033 - Zinc, [ethanedioato(2-)-. kappa. O1, . kappa. O2]-.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Zinc, [ethanedioato(2-)-. kappa. O1, . kappa. O2]-. 721.10033 Section 721.10033 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.1003...

  18. 40 CFR 721.10033 - Zinc, [ethanedioato(2-)-. kappa. O1, . kappa. O2]-.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Zinc, [ethanedioato(2-)-. kappa. O1, . kappa. O2]-. 721.10033 Section 721.10033 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.1003...

  19. 40 CFR 721.10033 - Zinc, [ethanedioato(2-)-. kappa. O1, . kappa. O2]-.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Zinc, [ethanedioato(2-)-. kappa. O1, . kappa. O2]-. 721.10033 Section 721.10033 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.1003...

  20. Homologous kappa-neurotoxins exhibit residue-specific interactions with the alpha 3 subunit of the nicotinic acetylcholine receptor: a comparison of the structural requirements for kappa-bungarotoxin and kappa-flavitoxin binding.

    PubMed

    McLane, K E; Weaver, W R; Lei, S; Chiappinelli, V A; Conti-Tronconi, B M

    1993-07-13

    kappa-Flavotoxin (kappa-FTX), a snake neurotoxin that is a selective antagonist of certain neuronal nicotinic acetylcholine receptors (AChRs), has recently been isolated and characterized [Grant, G. A., Frazier, M. W., & Chiappinelli, V. A. (1988) Biochemistry 27, 1532-1537]. Like the related snake toxin kappa-bungarotoxin (kappa-BTX), kappa-FTX binds with high affinity to alpha 3 subtypes of neuronal AChRs, even though there are distinct sequence differences between the two toxins. To further characterize the sequence regions of the neuronal AChR alpha 3 subunit involved in formation of the binding site for this family of kappa-neurotoxins, we investigated kappa-FTX binding to overlapping synthetic peptides screening the alpha 3 subunit sequence. A sequence region forming a "prototope" for kappa-FTX was identified within residues alpha 3 (51-70), confirming the suggestions of previous studies on the binding of kappa-BTX to the alpha 3 subunit [McLane, K. E., Tang, F., & Conti-Tronconi, B. M. (1990) J. Biol. Chem. 265, 1537-1544] and alpha-bungarotoxin to the Torpedo AChR alpha subunit [Conti-Tronconi, B. M., Tang, F., Diethelm, B. M., Spencer, S. R., Reinhardt-Maelicke, S., & Maelicke, A. (1990) Biochemistry 29, 6221-6230] that this sequence region is involved in formation of a cholinergic site. Single residue substituted analogues, where each residue of the sequence alpha 3 (51-70) was sequentially replaced by a glycine, were used to identify the amino acid side chains involved in the interaction of this prototope with kappa-FTX.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Porcine circovirus type 2 induces the activation of nuclear factor kappa B by I{kappa}B{alpha} degradation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wei Li; Kwang, Jimmy; Wang Jin

    The transcription factor NF-{kappa}B is commonly activated upon virus infection and a key player in the induction and regulation of the host immune response. The present study demonstrated for the first time that porcine circovirus type 2 (PCV2), which is the primary causative agent of an emerging swine disease, postweaning multisystemic wasting syndrome, can activate NF-{kappa}B in PCV2-infected PK15 cells. In PCV2-infected cells, NF-{kappa}B was activated concomitantly with viral replication, which was characterized by increased DNA binding activity, translocation of NF-{kappa}B p65 from the cytoplasm to the nucleus, as well as degradation and phosphorylation of I{kappa}B{alpha} protein. We further demonstratedmore » PCV2-induced activation of NF-{kappa}B and colocalization of p65 nuclear translocation with virus replication in cultured cells. Treatment of cells with CAPE, a selective inhibitor of NF-{kappa}B activation, reduced virus protein expression and progeny production followed by decreasing PCV2-induced apoptotic caspase activity, indicating the involvement of this transcription factor in induction of cell death. Taken together, these data suggest that NF-{kappa}B activation is important for PCV2 replication and contributes to virus-mediated changes in host cells. The results presented here provide a basis for understanding molecular mechanism of PCV2 infection.« less

  2. FBI-1 enhances transcription of the nuclear factor-kappaB (NF-kappaB)-responsive E-selectin gene by nuclear localization of the p65 subunit of NF-kappaB.

    PubMed

    Lee, Dong-Kee; Kang, Jae-Eun; Park, Hye-Jin; Kim, Myung-Hwa; Yim, Tae-Hee; Kim, Jung-Min; Heo, Min-Kyu; Kim, Kyu-Yeun; Kwon, Ho Jeong; Hur, Man-Wook

    2005-07-29

    The POZ domain is a highly conserved protein-protein interaction motif found in many regulatory proteins. Nuclear factor-kappaB (NF-kappaB) plays a key role in the expression of a variety of genes in response to infection, inflammation, and stressful conditions. We found that the POZ domain of FBI-1 (factor that binds to the inducer of short transcripts of human immunodeficiency virus-1) interacted with the Rel homology domain of the p65 subunit of NF-kappaB in both in vivo and in vitro protein-protein interaction assays. FBI-1 enhanced NF-kappaB-mediated transcription of E-selectin genes in HeLa cells upon phorbol 12-myristate 13-acetate stimulation and overcame gene repression by IkappaB alpha or IkappaB beta. In contrast, the POZ domain of FBI-1, which is a dominant-negative form of FBI-1, repressed NF-kappaB-mediated transcription, and the repression was cooperative with IkappaB alpha or IkappaB beta. In contrast, the POZ domain tagged with a nuclear localization sequence polypeptide of FBI-1 enhanced NF-kappaB-responsive gene transcription, suggesting that the molecular interaction between the POZ domain and the Rel homology domain of p65 and the nuclear localization by the nuclear localization sequence are important in the transcription enhancement mediated by FBI-1. Confocal microscopy showed that FBI-1 increased NF-kappaB movement into the nucleus and increased the stability of NF-kappaB in the nucleus, which enhanced NF-kappaB-mediated transcription of the E-selectin gene. FBI-1 also interacted with IkappaB alpha and IkappaB beta.

  3. The kappa statistic in rehabilitation research: an examination.

    PubMed

    Tooth, Leigh R; Ottenbacher, Kenneth J

    2004-08-01

    The number and sophistication of statistical procedures reported in medical rehabilitation research is increasing. Application of the principles and methods associated with evidence-based practice has contributed to the need for rehabilitation practitioners to understand quantitative methods in published articles. Outcomes measurement and determination of reliability are areas that have experienced rapid change during the past decade. In this study, distinctions between reliability and agreement are examined. Information is presented on analytical approaches for addressing reliability and agreement with the focus on the application of the kappa statistic. The following assumptions are discussed: (1) kappa should be used with data measured on a categorical scale, (2) the patients or objects categorized should be independent, and (3) the observers or raters must make their measurement decisions and judgments independently. Several issues related to using kappa in measurement studies are described, including use of weighted kappa, methods of reporting kappa, the effect of bias and prevalence on kappa, and sample size and power requirements for kappa. The kappa statistic is useful for assessing agreement among raters, and it is being used more frequently in rehabilitation research. Correct interpretation of the kappa statistic depends on meeting the required assumptions and accurate reporting.

  4. MicroRNA-22 and microRNA-140 suppress NF-{kappa}B activity by regulating the expression of NF-{kappa}B coactivators

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Takata, Akemi; Otsuka, Motoyuki, E-mail: otsukamo-tky@umin.ac.jp; Kojima, Kentaro

    2011-08-12

    Highlights: {yields} miRNAs were screened for their ability to regulate NF-{kappa}B activity. {yields} miRNA-22 and miRNA-140-3p suppress NF-{kappa}B activity by regulating coactivators. {yields} miRNA-22 targets nuclear receptor coactivator 1 (NCOA1). {yields} miRNA-140-3p targets nuclear receptor-interacting protein 1 (NRIP1). -- Abstract: Nuclear factor {kappa}B (NF-{kappa}B) is a transcription factor that regulates a set of genes that are critical to many biological phenomena, including liver tumorigenesis. To identify microRNAs (miRNAs) that regulate NF-{kappa}B activity in the liver, we screened 60 miRNAs expressed in hepatocytes for their ability to modulate NF-{kappa}B activity. We found that miRNA-22 and miRNA-140-3p significantly suppressed NF-{kappa}B activity bymore » regulating the expression of nuclear receptor coactivator 1 (NCOA1) and nuclear receptor-interacting protein 1 (NRIP1), both of which are NF-{kappa}B coactivators. Our results provide new information about the roles of miRNAs in the regulation of NF-{kappa}B activity.« less

  5. The effects of dexamethasone on rat brain cortical nuclear factor kappa B (NF-{kappa}B) in endotoxic shock

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang Zhi; Kang Jinsong; Li Yang

    2006-08-01

    To explore the molecular mechanism of brain tissue injury induced by lipopolysaccharide (LPS), we studied the effects of endotoxic shock on rat brain cortex NF-{kappa}B and the effects of dexamethasone on these changes. Rats were randomly divided into LPS, LPS + dexamethasone, and control groups. The DNA-binding activity of NF-{kappa}B was observed using electrophoretic mobility shift assay (EMSA). Protein expression in nuclear extracts was studied using Western blots, and nuclear translocation was observed using immunohistochemistry. These indices were assayed at 1 h and 4 h after intravenous injection of LPS (4 mg.kg{sup -1}). EMSA showed significantly increased NF-{kappa}B DNA-binding activitymore » in nuclear extracts from the LPS group at both 1 h and 4 h after LPS injection, compared with the control group (P < 0.01). For the LPS group, the NF-{kappa}B DNA-binding activity was greater at 1 h than at 4 h (P < 0.05). The expression of p65 and p50 protein in the nuclear extracts was also increased, as compared with the control group. However, the expression of p65 and p50 protein from cytosolic extracts did not show any significant change. Dexamethasone down-regulated not only NF-{kappa}B DNA-binding activity but also the expression of p65 protein in the nuclear extracts. From these data, we have concluded that NF-{kappa}B activation and nuclear translocation of NF-{kappa}B play a key role in the molecular mechanism of brain tissue injury in endotoxic shock. Dexamethasone may alleviate brain injury by inhibiting NF-{kappa}B activation.« less

  6. Statistical analysis of suprathermal electron drivers at 67P/Churyumov-Gerasimenko

    NASA Astrophysics Data System (ADS)

    Broiles, Thomas W.; Burch, J. L.; Chae, K.; Clark, G.; Cravens, T. E.; Eriksson, A.; Fuselier, S. A.; Frahm, R. A.; Gasc, S.; Goldstein, R.; Henri, P.; Koenders, C.; Livadiotis, G.; Mandt, K. E.; Mokashi, P.; Nemeth, Z.; Odelstad, E.; Rubin, M.; Samara, M.

    2016-11-01

    We use observations from the Ion and Electron Sensor (IES) on board the Rosetta spacecraft to study the relationship between the cometary suprathermal electrons and the drivers that affect their density and temperature. We fit the IES electron observations with the summation of two kappa distributions, which we characterize as a dense and warm population (˜10 cm-3 and ˜16 eV) and a rarefied and hot population (˜0.01 cm-3 and ˜43 eV). The parameters of our fitting technique determine the populations' density, temperature, and invariant kappa index. We focus our analysis on the warm population to determine its origin by comparing the density and temperature with the neutral density and magnetic field strength. We find that the warm electron population is actually two separate sub-populations: electron distributions with temperatures above 8.6 eV and electron distributions with temperatures below 8.6 eV. The two sub-populations have different relationships between their density and temperature. Moreover, the two sub-populations are affected by different drivers. The hotter sub-population temperature is strongly correlated with neutral density, while the cooler sub-population is unaffected by neutral density and is only weakly correlated with magnetic field strength. We suggest that the population with temperatures above 8.6 eV is being heated by lower hybrid waves driven by counterstreaming solar wind protons and newly formed, cometary ions created in localized, dense neutral streams. To the best of our knowledge, this represents the first observations of cometary electrons heated through wave-particle interactions.

  7. Kappa-receptor selective binding of opioid ligands with a heterocyclic bicyclo[3.3.1]nonan-9-one structure.

    PubMed

    Benyhe, S; Márki, A; Nachtsheim, Corina; Holzgrabe, Ulrike; Borsodi, Anna

    2003-01-01

    Previous pharmacological results have suggested that members of the heterocyclic bicyclo[3.3.1]nonan-9-one-like compounds are potent kappa-opioid receptor specific agonists. One lead molecule of this series. called compound 1 (dimethyl 7-methyl-2,4-di-2-pyridyl-3.7-diazabicyclo[3.3.1]nonan-9-one-1,5-dicarboxylate) exhibited high affinity for [3H]ethylketocyclazocine and [3H]U-69.593 binding sites in guinea pig cerebellar membranes which known to be a good source for kappa1 receptors. It was shown by molecular modelling that heterocyclic bicyclo[3.3.1]nonan-9-ones fit very well with the structure of ketazocine, a prototypic kappa-selective benzomorphan compound; when compared to the arylacetamide structure of U-69.593, a specific kappa1-receptor agonist, a similar geometry was found with a slightly different distribution of the charges. It is postulated, that the essential structural skeleton involved in the opioid activity is an aryl-propyl-amine element distributed along the N7-C6-C5-C4-aryl bonds.

  8. Electron acoustic nonlinear structures in planetary magnetospheres

    NASA Astrophysics Data System (ADS)

    Shah, K. H.; Qureshi, M. N. S.; Masood, W.; Shah, H. A.

    2018-04-01

    In this paper, we have studied linear and nonlinear propagation of electron acoustic waves (EAWs) comprising cold and hot populations in which the ions form the neutralizing background. The hot electrons have been assumed to follow the generalized ( r , q ) distribution which has the advantage that it mimics most of the distribution functions observed in space plasmas. Interestingly, it has been found that unlike Maxwellian and kappa distributions, the electron acoustic waves admit not only rarefactive structures but also allow the formation of compressive solitary structures for generalized ( r , q ) distribution. It has been found that the flatness parameter r , tail parameter q , and the nonlinear propagation velocity u affect the propagation characteristics of nonlinear EAWs. Using the plasmas parameters, typically found in Saturn's magnetosphere and the Earth's auroral region, where two populations of electrons and electron acoustic solitary waves (EASWs) have been observed, we have given an estimate of the scale lengths over which these nonlinear waves are expected to form and how the size of these structures would vary with the change in the shape of the distribution function and with the change of the plasma parameters.

  9. A Note on the Interpretation of Weighted Kappa and its Relations to Other Rater Agreement Statistics for Metric Scales

    ERIC Educational Resources Information Center

    Schuster, Christof

    2004-01-01

    This article presents a formula for weighted kappa in terms of rater means, rater variances, and the rater covariance that is particularly helpful in emphasizing that weighted kappa is an absolute agreement measure in the sense that it is sensitive to differences in rater's marginal distributions. Specifically, rater mean differences will decrease…

  10. Coupled ion acoustic and drift waves in magnetized superthermal electron-positron-ion plasmas

    NASA Astrophysics Data System (ADS)

    Adnan, Muhammad; Mahmood, S.; Qamar, Anisa

    2014-09-01

    Linear and nonlinear coupled drift-ion acoustic waves are investigated in a nonuniform magnetoplasma having kappa distributed electrons and positrons. In the linear regime, the role of kappa distribution and positron content on the dispersion relation has been highlighted; it is found that strong superthermality (low value of κ) and addition of positrons lowers the phase velocity via decreasing the fundamental scalelengths of the plasmas. In the nonlinear regime, first, coherent nonlinear structure in the form of dipoles and monopoles are obtained and the boundary conditions (boundedness) in the context of superthermality and positron concentrations are discussed. Second, in case of scalar nonlinearity, a Korteweg-de Vries-type equation is obtained, which admit solitary wave solution. It is found that both compressive and rarefactive solitons are formed in the present model. The present work may be useful to understand the low frequency electrostatic modes in inhomogeneous electron positron ion plasmas, which exist in astrophysical plasma situations such as those found in the pulsar magnetosphere.

  11. Some Paradoxical Results for the Quadratically Weighted Kappa

    ERIC Educational Resources Information Center

    Warrens, Matthijs J.

    2012-01-01

    The quadratically weighted kappa is the most commonly used weighted kappa statistic for summarizing interrater agreement on an ordinal scale. The paper presents several properties of the quadratically weighted kappa that are paradoxical. For agreement tables with an odd number of categories "n" it is shown that if one of the raters uses the same…

  12. Electron-phonon relaxation and excited electron distribution in gallium nitride

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhukov, V. P.; Donostia International Physics Center; Tyuterev, V. G., E-mail: valtyut00@mail.ru

    2016-08-28

    We develop a theory of energy relaxation in semiconductors and insulators highly excited by the long-acting external irradiation. We derive the equation for the non-equilibrium distribution function of excited electrons. The solution for this function breaks up into the sum of two contributions. The low-energy contribution is concentrated in a narrow range near the bottom of the conduction band. It has the typical form of a Fermi distribution with an effective temperature and chemical potential. The effective temperature and chemical potential in this low-energy term are determined by the intensity of carriers' generation, the speed of electron-phonon relaxation, rates ofmore » inter-band recombination, and electron capture on the defects. In addition, there is a substantial high-energy correction. This high-energy “tail” largely covers the conduction band. The shape of the high-energy “tail” strongly depends on the rate of electron-phonon relaxation but does not depend on the rates of recombination and trapping. We apply the theory to the calculation of a non-equilibrium distribution of electrons in an irradiated GaN. Probabilities of optical excitations from the valence to conduction band and electron-phonon coupling probabilities in GaN were calculated by the density functional perturbation theory. Our calculation of both parts of distribution function in gallium nitride shows that when the speed of the electron-phonon scattering is comparable with the rate of recombination and trapping then the contribution of the non-Fermi “tail” is comparable with that of the low-energy Fermi-like component. So the high-energy contribution can essentially affect the charge transport in the irradiated and highly doped semiconductors.« less

  13. Stimulated Mirror Instability From the Interplay of Anisotropic Protons and Electrons, and their Suprathermal Populations

    NASA Astrophysics Data System (ADS)

    Shaaban, S. M.; Lazar, M.; Astfalk, P.; Poedts, S.

    2018-03-01

    Mirror instability driven by the temperature anisotropy of protons can offer a plausible explanation for the mirror-like fluctuations observed in planetary magnetosheaths. In the present paper we invoke a realistic kinetic approach which can reproduce nonthermal features of plasma particles reported by the observations, i.e., temperature anisotropies and suprathermal populations. Seeking accuracy, a numerical analysis is performed using an advanced code named DSHARK, recently proposed to resolve the linear dispersion and stability for an arbitrary propagation in bi-Kappa distributed electron-proton plasmas. The stimulating effect of the anisotropic bi-Maxwellian electrons reported in Remya et al. (2013, https://doi.org/10.1002/jgra.50091) is markedly enhanced in the presence of suprathermal electrons described by the bi-Kappa distribution functions. The influence of suprathermal protons is more temperate, but overall, present results demonstrate that these sources of free energy provide natural conditions for a stimulated mirror instability, more efficient than predicted before and capable to compete with other instabilities (e.g., the electromagnetic ion-cyclotron instability) and mechanisms of relaxation.

  14. Resampling probability values for weighted kappa with multiple raters.

    PubMed

    Mielke, Paul W; Berry, Kenneth J; Johnston, Janis E

    2008-04-01

    A new procedure to compute weighted kappa with multiple raters is described. A resampling procedure to compute approximate probability values for weighted kappa with multiple raters is presented. Applications of weighted kappa are illustrated with an example analysis of classifications by three independent raters.

  15. Electron and ion distribution functions in magnetopause reconnection

    NASA Astrophysics Data System (ADS)

    Wang, S.; Chen, L. J.; Bessho, N.; Hesse, M.; Kistler, L. M.; Torbert, R. B.; Mouikis, C.; Pollock, C. J.

    2015-12-01

    We investigate electron and ion velocity distribution functions in dayside magnetopause reconnection events observed by the Cluster and MMS spacecraft. The goal is to build a spatial map of electron and ion distribution features to enable the indication of the spacecraft location in the reconnection structure, and to understand plasma energization processes. Distribution functions, together with electromagnetic field structures, plasma densities, and bulk velocities, are organized and compared with particle-in-cell simulation results to indicate the proximities to the reconnection X-line. Anisotropic features in the distributions of magnetospheric- and magnetosheath- origin electrons at different locations in the reconnection inflow and exhaust are identified. In particular, parallel electron heating is observed in both the magnetosheath and magnetosphere inflow regions. Possible effects of the guide field strength, waves, and upstream density and temperature asymmetries on the distribution features will be discussed.

  16. Terawatt x-ray free-electron-laser optimization by transverse electron distribution shaping

    DOE PAGES

    Emma, C.; Wu, J.; Fang, K.; ...

    2014-11-03

    We study the dependence of the peak power of a 1.5 Å Terawatt (TW), tapered x-ray free-electron laser (FEL) on the transverse electron density distribution. Multidimensional optimization schemes for TW hard x-ray free-electron lasers are applied to the cases of transversely uniform and parabolic electron beam distributions and compared to a Gaussian distribution. The optimizations are performed for a 200 m undulator and a resonant wavelength of λ r = 1.5 Å using the fully three-dimensional FEL particle code GENESIS. The study shows that the flatter transverse electron distributions enhance optical guiding in the tapered section of the undulator andmore » increase the maximum radiation power from a maximum of 1.56 TW for a transversely Gaussian beam to 2.26 TW for the parabolic case and 2.63 TW for the uniform case. Spectral data also shows a 30%–70% reduction in energy deposited in the sidebands for the uniform and parabolic beams compared with a Gaussian. An analysis of the transverse coherence of the radiation shows the coherence area to be much larger than the beam spotsize for all three distributions, making coherent diffraction imaging experiments possible.« less

  17. Measurement of Angle Kappa Using Ultrasound Biomicroscopy and Corneal Topography

    PubMed Central

    Yeo, Joon Hyung; Moon, Nam Ju

    2017-01-01

    Purpose To introduce a new convenient and accurate method to measure the angle kappa using ultrasound biomicroscopy (UBM) and corneal topography. Methods Data from 42 eyes (13 males and 29 females) were analyzed in this study. The angle kappa was measured using Orbscan II and calculated with UBM and corneal topography. The angle kappa of the dominant eye was compared with measurements by Orbscan II. Results The mean patient age was 36.4 ± 13.8 years. The average angle kappa measured by Orbscan II was 3.98° ± 1.12°, while the average angle kappa calculated with UBM and corneal topography was 3.19° ± 1.15°. The difference in angle kappa measured by the two methods was statistically significant (p < 0.001). The two methods showed good reliability (intraclass correlation coefficient, 0.671; p < 0.001). Bland-Altman plots were used to demonstrate the agreement between the two methods. Conclusions We designed a new method using UBM and corneal topography to calculate the angle kappa. This method is convenient to use and allows for measurement of the angle kappa without an expensive device. PMID:28471103

  18. Measurement of Angle Kappa Using Ultrasound Biomicroscopy and Corneal Topography.

    PubMed

    Yeo, Joon Hyung; Moon, Nam Ju; Lee, Jeong Kyu

    2017-06-01

    To introduce a new convenient and accurate method to measure the angle kappa using ultrasound biomicroscopy (UBM) and corneal topography. Data from 42 eyes (13 males and 29 females) were analyzed in this study. The angle kappa was measured using Orbscan II and calculated with UBM and corneal topography. The angle kappa of the dominant eye was compared with measurements by Orbscan II. The mean patient age was 36.4 ± 13.8 years. The average angle kappa measured by Orbscan II was 3.98° ± 1.12°, while the average angle kappa calculated with UBM and corneal topography was 3.19° ± 1.15°. The difference in angle kappa measured by the two methods was statistically significant (p < 0.001). The two methods showed good reliability (intraclass correlation coefficient, 0.671; p < 0.001). Bland-Altman plots were used to demonstrate the agreement between the two methods. We designed a new method using UBM and corneal topography to calculate the angle kappa. This method is convenient to use and allows for measurement of the angle kappa without an expensive device. © 2017 The Korean Ophthalmological Society

  19. NF-kappaB modulators from Valeriana officinalis.

    PubMed

    Jacobo-Herrera, Nadia J; Vartiainen, Nina; Bremner, Paul; Gibbons, Simon; Koistinaho, Jari; Heinrich, Michael

    2006-10-01

    Valeriana officinalis (Valerianaceae) has been of great interest for its therapeutic uses for treating mild nervous tension and temporary sleeping problems. In traditional European medicine it has been also reported as an antiinflammatory remedy. This study reports that the EtOAc extract of the underground parts of V. officinalis showed inhibitory activity against NF-kappaB at 100 microg/mL in the IL-6/Luc assay on HeLa cells and provided protection against excitotoxicity in primary brain cell cultures at micromolar concentrations. Bioassay-guided fractionation of the EtOAc extract led to the isolation of three known sesquiterpenes: acetylvalerenolic acid (1), valerenal (2) and valerenic acid (3), 1 and 3 were active as inhibitors of NF-kappaB at a concentration of 100 microg/mL. Acetylvalerenolic acid (1) reduced NF-kappaB activity to 4%, whereas valerenic acid (3) reduced NF-kappaB activity to 25%. Copyright 2006 John Wiley & Sons, Ltd.

  20. Power distribution for electron beam welding

    NASA Technical Reports Server (NTRS)

    Edwards, E.

    1980-01-01

    The power distribution of an electron seam is analyzed. Digital computer techniques are used to evaluate the radial distribution of power detected by a wire probe circulating through the beam. Results are reported.

  1. NF-kappaB mediates FGF signal regulation of msx-1 expression.

    PubMed

    Bushdid, P B; Chen, C L; Brantley, D M; Yull, F; Raghow, R; Kerr, L D; Barnett, J V

    2001-09-01

    The nuclear factor-kappaB (NF-kappaB) family of transcription factors is involved in proliferation, differentiation, and apoptosis in a stage- and cell-dependent manner. Recent evidence has shown that NF-kappaB activity is necessary for both chicken and mouse limb development. We report here that the NF-kappaB family member c-rel and the homeodomain gene msx-1 have partially overlapping expression patterns in the developing chick limb. In addition, inhibition of NF-kappaB activity resulted in a decrease in msx-1 mRNA expression. Sequence analysis of the msx-1 promoter revealed three potential kappaB-binding sites similar to the interferon-gamma (IFN-gamma) kappaB-binding site. These sites bound to c-Rel, as shown by electrophoretic mobility shift assay (EMSA). Furthermore, inhibition of NF-kappaB activity significantly reduced transactivation of the msx-1 promoter in response to FGF-2/-4, known stimulators of msx-1 expression. These results suggest that NF-kappaB mediates the FGF-2/-4 signal regulation of msx-1 gene expression. Copyright 2001 Academic Press.

  2. Nonlinear structure formation in ion-temperature-gradient driven drift waves in pair-ion plasma with nonthermal electron distribution

    NASA Astrophysics Data System (ADS)

    Razzaq, Javaria; Haque, Q.; Khan, Majid; Bhatti, Adnan Mehmood; Kamran, M.; Mirza, Arshad M.

    2018-02-01

    Nonlinear structure formation in ion-temperature-gradient (ITG) driven waves is investigated in pair-ion plasma comprising ions and nonthermal electrons (kappa, Cairns). By using the transport equations of the Braginskii model, a new set of nonlinear equations are derived. A linear dispersion relation is obtained and discussed analytically as well as numerically. It is shown that the nonthermal population of electrons affects both the linear and nonlinear characteristics of the ITG mode in pair-ion plasma. This work will be useful in tokamaks and stellarators where non-Maxwellian population of electrons may exist due to resonant frequency heating, electron cyclotron heating, runaway electrons, etc.

  3. Depletion of the cellular levels of Bag-1 proteins attenuates phorbol ester-induced downregulation of I{kappa}B{alpha} and nuclear accumulation of NF-{kappa}B

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Maier, Jana V., E-mail: Jana.maier@kit.edu; Volz, Yvonne; Berger, Caroline

    2010-10-22

    Research highlights: {yields}Bag-1 depletion only marginally affects the action of the glucocorticoid receptor but strongly regulates the activity of NF-{kappa}B. {yields}Bag-1 depletion attenuates phosphorylation and degradation of I{kappa}B{alpha} and nuclear accumulation of NF-{kappa}B p65 and p50. {yields}Bag-1 interacts with I{kappa}B{alpha} and partially restores I{kappa}B{alpha} and NF-{kappa}B activation in Bag-1 depleted cells. -- Abstract: Bag-1 consists in humans of four isoforms generated from the same RNA by alternative translation. Overexpression of single Bag-1 isoforms has identified Bag-1 as a negative regulator of action of many proteins including the glucocorticoid receptor (GR). Here we have analysed the ability of Bag-1 to regulatemore » the transrepression function of the GR. Silencing Bag-1 expression only marginally affects the transrepression action of the GR but decreased the action of the transcription factor NF-{kappa}B. Furthermore phosphorylation and degradation of the inhibitor protein I{kappa}B{alpha} and nuclear accumulation of p65 and p50 NF-{kappa}B proteins in response to phorbol ester was attenuated following Bag-1 depletion in HeLa cells. Reconstitution of Bag-1 in depleted cells partially restored I{kappa}B{alpha} and NF-{kappa}B activation. Knock-down of Bag-1 expression also did not significantly alter GR-mediated transactivation but affected the basal transcription of some of the target genes. Thus Bag-1 proteins function as regulators of the action of selective transcription factors.« less

  4. NF-{kappa}B regulates Lef1 gene expression in chondrocytes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yun, Kangsun; Choi, Yoo Duk; Nam, Jong Hee

    The relation of Wnt/{beta}-catenin signaling to osteoarthritis progression has been revealed with little information on the underlying molecular mechanism. In this study we found overexpression of Lef1 in cartilage tissue of osteoarthritic patients and elucidated molecular mechanism of NF-{kappa}B-mediated Lef1 gene regulation in chondrocytes. Treatment of IL-1{beta} augmented Lef1 upregulation and nuclear translocation of NF-{kappa}B in chondrocytes. Under IL-1{beta} signaling, treatment of NF-{kappa}B nuclear translocation inhibitor SN-50 reduced Lef1 expression. A conserved NF-{kappa}B-binding site between mouse and human was selected through bioinformatic analysis and mapped at the 14 kb upstream of Lef1 transcription initiation site. NF-{kappa}B binding to the sitemore » was confirmed by chromatin immunoprecipitation assay. Lef1 expression was synergistically upregulated by interactions of NF-{kappa}B with Lef1/{beta}-catenin in chondrocytes. Our results suggest a pivotal role of NF-{kappa}B in Lef1 expression in arthritic chondrocytes or cartilage degeneration.« less

  5. IKK{epsilon} modulates RSV-induced NF-{kappa}B-dependent gene transcription

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bao Xiaoyong; Indukuri, Hemalatha; Liu Tianshuang

    2010-12-20

    Respiratory syncytial virus (RSV), a negative-strand RNA virus, is the most common cause of epidemic respiratory disease in infants and young children. RSV infection of airway epithelial cells induces the expression of immune/inflammatory genes through the activation of a subset of transcription factors, including Nuclear Factor-{kappa}B (NF-{kappa}B). In this study we have investigated the role of the non canonical I{kappa}B kinase (IKK){epsilon} in modulating RSV-induced NF-{kappa}B activation. Our results show that inhibition of IKK{epsilon} activation results in significant impairment of viral-induced NF-{kappa}B-dependent gene expression, through a reduction in NF-{kappa}B transcriptional activity, without changes in nuclear translocation or DNA-binding activity. Absencemore » of IKK{epsilon} results in a significant decrease of RSV-induced NF-{kappa}B phosphorylation on serine 536, a post-translational modification important for RSV-induced NF-{kappa}B-dependent gene expression, known to regulate NF-{kappa}B transcriptional activity without affecting nuclear translocation. This study identifies a novel mechanism by which IKK{epsilon} regulates viral-induced cellular signaling.« less

  6. Universality of Electron Distributions in Extensive Air Showers

    NASA Astrophysics Data System (ADS)

    Śmiałkowski, Andrzej; Giller, Maria

    2018-02-01

    Based on extensive air shower simulations, it is shown that electron distributions with respect to two angles determining the electron direction at a given shower age, for a fixed electron energy and lateral distance, are universal. This means that the distributions do not depend on the primary particle energy or mass (thus, neither on the interaction model), shower zenith angle, or shower to shower fluctuations, if they are taken at the same shower age. Together with previous work showing the universality of the distributions of the electron energy, lateral distance (integrated over angles), and angle (integrated over lateral distance) for fixed electron energy, this paper completes a full universal description of the electron states at various shower ages. Analytical parametrizations of the full electron states are given. It is also shown that some distributions can be described by a number of variables smaller than five, with the new ones being products of old ones raised to some power. The accuracy of the present parametrization is sufficiently good to apply to showers with a primary energy uncertainty of 14% (as is the case at the Pierre Auger Observatory). The shower fluctuations in the chosen bins of the multidimensional variable space are about 6%, determining the minimum uncertainty needed for the parametrization of the universal distributions. An analytical way of estimating the effect of the geomagnetic field is given. Thanks to the universality of the electron distribution in any shower, a new method of shower reconstruction can be worked out from the data from observatories using the fluorescence technique. The light fluxes (both fluorescence and Cherenkov) for any shower age can be exactly predicted for a shower with any primary energy and shower maximum depth, so that the two quantities can be obtained by best fitting the predictions to the measurements.

  7. Kappa angles in different positions in patients with myopia during LASIK

    PubMed Central

    Qi, Hui; Jiang, Jing-Jing; Jiang, Yan-Ming; Wang, Li-Qiang; Huang, Yi-Fei

    2016-01-01

    AIM To investigate the difference in kappa angle between sitting and supine positions during laser-assisted in situ keratomileusis (LASIK). METHODS A retrospective study was performed on 395 eyes from 215 patients with myopia that received LASIK. Low, moderate, and high myopia groups were assigned according to diopters. The horizontal and vertical components of kappa angle in sitting position were measured before the operation, and in supine position during the operation. The data from the two positions were compared and the relationship between kappa angle and diopters were analyzed. RESULTS Two hundred and twenty-three eyes (56.5%) in sitting position and 343 eyes (86.8%) in supine position had positive kappa angles. There were no significant differences in horizontal and vertical components of kappa angle in the sitting position or horizontal components of kappa angle in the supine position between the three groups (P>0.05). A significant difference in the vertical components of kappa angle in the supine position was seen in the three groups (P<0.01). Differences in both horizontal and vertical components of kappa angles were significant between the sitting and supine positions. Positive correlations in both horizontal and vertical components of kappa angles (P<0.05) were found and vertical components of kappa angle in sitting and supine positions were negatively correlated with the degree of myopia (sitting position: r=-0.109; supine position: r=-0.172; P<0.05). CONCLUSION There is a correlation in horizontal and vertical components of kappa angle in sitting and supine positions. Positive correlations in both horizontal and vertical components of kappa angle in sitting and supine positions till the end of the results. This result still needs further observation. Clinicians should take into account different postures when excimer laser surgery needs to be performed. PMID:27162734

  8. Impact of distributed power electronics on the lifetime and reliability of PV systems: Impact of distributed power electronics

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Olalla, Carlos; Maksimovic, Dragan; Deline, Chris

    Here, this paper quantifies the impact of distributed power electronics in photovoltaic (PV) systems in terms of end-of-life energy-capture performance and reliability. The analysis is based on simulations of PV installations over system lifetime at various degradation rates. It is shown how module-level or submodule-level power converters can mitigate variations in cell degradation over time, effectively increasing the system lifespan by 5-10 years compared with the nominal 25-year lifetime. An important aspect typically overlooked when characterizing such improvements is the reliability of distributed power electronics, as power converter failures may not only diminish energy yield improvements but also adversely affectmore » the overall system operation. Failure models are developed, and power electronics reliability is taken into account in this work, in order to provide a more comprehensive view of the opportunities and limitations offered by distributed power electronics in PV systems. Lastly, it is shown how a differential power-processing approach achieves the best mismatch mitigation performance and the least susceptibility to converter faults.« less

  9. Impact of distributed power electronics on the lifetime and reliability of PV systems: Impact of distributed power electronics

    DOE PAGES

    Olalla, Carlos; Maksimovic, Dragan; Deline, Chris; ...

    2017-04-26

    Here, this paper quantifies the impact of distributed power electronics in photovoltaic (PV) systems in terms of end-of-life energy-capture performance and reliability. The analysis is based on simulations of PV installations over system lifetime at various degradation rates. It is shown how module-level or submodule-level power converters can mitigate variations in cell degradation over time, effectively increasing the system lifespan by 5-10 years compared with the nominal 25-year lifetime. An important aspect typically overlooked when characterizing such improvements is the reliability of distributed power electronics, as power converter failures may not only diminish energy yield improvements but also adversely affectmore » the overall system operation. Failure models are developed, and power electronics reliability is taken into account in this work, in order to provide a more comprehensive view of the opportunities and limitations offered by distributed power electronics in PV systems. Lastly, it is shown how a differential power-processing approach achieves the best mismatch mitigation performance and the least susceptibility to converter faults.« less

  10. Synchrotron radiation from a runaway electron distribution in tokamaks

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Stahl, A.; Fülöp, T.; Landreman, M.

    2013-09-15

    The synchrotron radiation emitted by runaway electrons in a fusion plasma provides information regarding the particle momenta and pitch-angles of the runaway electron population through the strong dependence of the synchrotron spectrum on these parameters. Information about the runaway density and its spatial distribution, as well as the time evolution of the above quantities, can also be deduced. In this paper, we present the synchrotron radiation spectra for typical avalanching runaway electron distributions. Spectra obtained for a distribution of electrons are compared with the emission of mono-energetic electrons with a prescribed pitch-angle. We also examine the effects of magnetic fieldmore » curvature and analyse the sensitivity of the resulting spectrum to perturbations to the runaway distribution. The implications for the deduced runaway electron parameters are discussed. We compare our calculations to experimental data from DIII-D and estimate the maximum observed runaway energy.« less

  11. Antiinflammatory effects of glucocorticoids in brain cells, independent of NF-kappa B.

    PubMed

    Bourke, E; Moynagh, P N

    1999-08-15

    Glucocorticoids are potent antiinflammatory drugs. They inhibit the expression of proinflammatory cytokines and adhesion molecules. It has recently been proposed that the underlying basis to such inhibition is the induction of the protein I kappa B, which inhibits the transcription factor NF-kappa B. The latter is a key activator of the genes encoding cytokines and adhesion molecules. The present study shows that the synthetic glucocorticoid, dexamethasone, inhibits the induction of the proinflammatory cytokine IL-8 and the adhesion molecules VCAM-1 and ICAM-1 in human 1321N1 astrocytoma and SK.N.SH neuroblastoma cells. However, dexamethasone failed to induce I kappa B or inhibit activation of NF-kappa B by IL-1 in the two cell types. EMSA confirmed the identity of the activated NF-kappa B by demonstrating that an oligonucleotide, containing the wild-type NF-kappa B-binding motif, inhibited formation of the NF-kappa B-DNA complexes whereas a mutated form of the NF-kappa B-binding motif was ineffective. In addition, supershift analysis showed that the protein subunits p50 and p65 were prevalent components in the activated NF-kappa B complexes. The lack of effect of dexamethasone on the capacity of IL-1 to activate NF-kappa B correlated with its inability to induce I kappa B and the ability of IL-1 to cause degradation of I kappa B, even in the presence of dexamethasone. The results presented in this paper strongly suggest that glucocorticoids may exert antiinflammatory effects in cells of neural origin by a mechanism(s) independent of NF-kappa B.

  12. Beam distribution reconstruction simulation for electron beam probe

    NASA Astrophysics Data System (ADS)

    Feng, Yong-Chun; Mao, Rui-Shi; Li, Peng; Kang, Xin-Cai; Yin, Yan; Liu, Tong; You, Yao-Yao; Chen, Yu-Cong; Zhao, Tie-Cheng; Xu, Zhi-Guo; Wang, Yan-Yu; Yuan, You-Jin

    2017-07-01

    An electron beam probe (EBP) is a detector which makes use of a low-intensity and low-energy electron beam to measure the transverse profile, bunch shape, beam neutralization and beam wake field of an intense beam with small dimensions. While it can be applied to many aspects, we limit our analysis to beam distribution reconstruction. This kind of detector is almost non-interceptive for all of the beam and does not disturb the machine environment. In this paper, we present the theoretical aspects behind this technique for beam distribution measurement and some simulation results of the detector involved. First, a method to obtain a parallel electron beam is introduced and a simulation code is developed. An EBP as a profile monitor for dense beams is then simulated using the fast scan method for various target beam profiles, including KV distribution, waterbag distribution, parabolic distribution, Gaussian distribution and halo distribution. Profile reconstruction from the deflected electron beam trajectory is implemented and compared with the actual profile, and the expected agreement is achieved. Furthermore, as well as fast scan, a slow scan, i.e. step-by-step scan, is considered, which lowers the requirement for hardware, i.e. Radio Frequency deflector. We calculate the three-dimensional electric field of a Gaussian distribution and simulate the electron motion in this field. In addition, a fast scan along the target beam direction and slow scan across the beam are also presented, and can provide a measurement of longitudinal distribution as well as transverse profile simultaneously. As an example, simulation results for the China Accelerator Driven Sub-critical System (CADS) and High Intensity Heavy Ion Accelerator Facility (HIAF) are given. Finally, a potential system design for an EBP is described.

  13. Distribution of tunnelling times for quantum electron transport.

    PubMed

    Rudge, Samuel L; Kosov, Daniel S

    2016-03-28

    In electron transport, the tunnelling time is the time taken for an electron to tunnel out of a system after it has tunnelled in. We define the tunnelling time distribution for quantum processes in a dissipative environment and develop a practical approach for calculating it, where the environment is described by the general Markovian master equation. We illustrate the theory by using the rate equation to compute the tunnelling time distribution for electron transport through a molecular junction. The tunnelling time distribution is exponential, which indicates that Markovian quantum tunnelling is a Poissonian statistical process. The tunnelling time distribution is used not only to study the quantum statistics of tunnelling along the average electric current but also to analyse extreme quantum events where an electron jumps against the applied voltage bias. The average tunnelling time shows distinctly different temperature dependence for p- and n-type molecular junctions and therefore provides a sensitive tool to probe the alignment of molecular orbitals relative to the electrode Fermi energy.

  14. Positron Annihilation Studies of the Electronic Structure of Selected High-Temperature Cuprate and Organic Superconductors.

    NASA Astrophysics Data System (ADS)

    Chan, Lie Ping

    The understanding of the electronic structure of the high-T_{c} superconductors could be important for a full theoretical description of the mechanism behind superconductivity in these materials. In this thesis, we present our measurements of the positron -electron momentum distributions of the cuprate superconductors Bi_2Sr_2CaCu _2O_8, Tl _2Ba_2Ca _2Cu_3O_ {10}, and the organic superconductor kappa-(BEDT)_2Cu(NCS) _2. We use the positron Two-dimensional Angular Correlation of Annihilation Radiation technique to make the measurements on single crystals and compare our high-statistics data with band structure calculations to determine the existence and nature of the respective Fermi surfaces. The spectra from unannealed Bi _2Sr_2CaCu _2O_8 exhibit effects of the superlattice modulation in the BiO_2 layers, and a theoretical understanding of the modulation effects on the electronic band structure is required to interpret these spectra. Since the present theory does not consider the modulation, we have developed a technique to remove the modulation effects from our spectra, and the resultant data when compared with the positron -electron momentum distribution calculation, yield features consistent with the predicted CuO_2 and BiO_2 Fermi surfaces. In the data from unannealed Tl_2Ba _2Ca_2Cu_3 O_{10}, we only observe indications of the TlO Fermi surfaces, and attribute the absence of the predicted CuO_2 Fermi surfaces to the poor sample quality. In the absence of positron-electron momentum calculations for kappa-(BEDT)_2Cu(NCS) _2, we compare our data to electronic band structure calculations, and observed features suggestive of the predicted Fermi surface contributions from the BEDT cation layers. A complete positron-electron calculation for kappa-(BEDT)_2 Cu(NCS)_2 is required to understand the positron wavefunction effects in this material.

  15. Electron Distribution Functions in the Diffusion Region of Asymmetric Magnetic Reconnection

    NASA Technical Reports Server (NTRS)

    Bessho, N.; Chen, L.-J.; Hesse, M.

    2016-01-01

    We study electron distribution functions in a diffusion region of antiparallel asymmetric reconnection by means of particle-in-cell simulations and analytical theory. At the electron stagnation point, the electron distribution comprises a crescent-shaped population and a core component. The crescent-shaped distribution is due to electrons coming from the magnetosheath toward the stagnation point and accelerated mainly by electric field normal to the current sheet. Only a part of magnetosheath electrons can reach the stagnation point and form the crescent-shaped distribution that has a boundary of a parabolic curve. The penetration length of magnetosheath electrons into the magnetosphere is derived. We expect that satellite observations can detect crescent-shaped electron distributions during magnetopause reconnection.

  16. The Correlation between Angle Kappa and Ocular Biometry in Koreans

    PubMed Central

    Choi, Se Rang

    2013-01-01

    Purpose To investigate normative angle kappa data and to examine whether correlations exist between angle kappa and ocular biometric measurements (e.g., refractive error, axial length) and demographic features in Koreans. Methods Data from 436 eyes (213 males and 223 females) were analyzed in this study. The angle kappa was measured using Orbscan II. We used ocular biometric measurements, including refractive spherical equivalent, interpupillary distance and axial length, to investigate the correlations between angle kappa and ocular biometry. The IOL Master ver. 5.02 was used to obtain axial length. Results The mean patient age was 57.5 ± 12.0 years in males and 59.4 ± 12.4 years in females (p = 0.11). Angle kappa averaged 4.70 ± 2.70 degrees in men and 4.89 ± 2.14 degrees in women (p = 0.48). Axial length and spherical equivalent were correlated with angle kappa (r = -0.342 and r = 0.197, respectively). The correlation between axial length and spherical equivalent had a negative correlation (r = -0.540, p < 0.001). Conclusions Angle kappa increased with spherical equivalent and age. Thus, careful manipulation should be considered in older and hyperopic patients when planning refractive or strabismus surgery. PMID:24311927

  17. Inhibition of single Shaker K channels by kappa-conotoxin-PVIIA.

    PubMed Central

    Naranjo, David

    2002-01-01

    kappa-Conotoxin-PVIIA (kappa-PVIIA) is a 27-residue basic (+4) peptide from the venom of the predator snail Conus purpurascens. A single kappa-PVIIA molecule interrupts ion conduction by binding to the external mouth of Shaker K channels. The blockade of Shaker by kappa-PVIIA was studied at the single channel level in membrane patches from Xenopus oocytes. The amplitudes of blocked and closed events were undistinguishable, suggesting that the toxin interrupts ion conduction completely. Between -20 and 40 mV kappa-PVIIA increased the latency to the first opening by one order of magnitude in a concentration-independent fashion. Because kappa-PVIIA has higher affinity for the closed channels at high enough concentration to block >90% of the resting channels, the dissociation rate could be estimated from the analysis of the first latency. At 0 mV, the dissociation rate was 20 s(-1) and had an effective valence of 0.64. The apparent closing rate increased linearly with [kappa-PVIIA] indicating an association rate of 56 microM(-1) s(-1). The toxin did not modify the fraction of null traces. This result suggests that the structural rearrangements in the external mouth contributing to the slow inactivation preserve the main geometrical features of the toxin-receptor interaction. PMID:12023223

  18. Resistance distribution in the hopping percolation model.

    PubMed

    Strelniker, Yakov M; Havlin, Shlomo; Berkovits, Richard; Frydman, Aviad

    2005-07-01

    We study the distribution function P (rho) of the effective resistance rho in two- and three-dimensional random resistor networks of linear size L in the hopping percolation model. In this model each bond has a conductivity taken from an exponential form sigma proportional to exp (-kappar) , where kappa is a measure of disorder and r is a random number, 0< or = r < or =1 . We find that in both the usual strong-disorder regime L/ kappa(nu) >1 (not sensitive to removal of any single bond) and the extreme-disorder regime L/ kappa(nu) <1 (very sensitive to such a removal) the distribution depends only on L/kappa(nu) and can be well approximated by a log-normal function with dispersion b kappa(nu) /L , where b is a coefficient which depends on the type of lattice, and nu is the correlation critical exponent.

  19. c-rel activates but v-rel suppresses transcription from kappa B sites.

    PubMed Central

    Inoue, J; Kerr, L D; Ransone, L J; Bengal, E; Hunter, T; Verma, I M

    1991-01-01

    We show that the product of the protooncogene c-rel is a constituent of an NF-kappa B-like complex that binds to the kappa B site originally identified in the enhancer of immunoglobulin kappa light chain gene. c-rel protein synthesized in bacteria binds to the kappa B site in a sequence-specific manner. The rel-kappa B complex can be disrupted by incubation with anti-rel antibodies. The rel protein can form oligomers. The c-rel protein can activate transcription from promoters containing kappa B sites; v-rel, on the other hand, suppresses the transcription of genes linked to kappa B sites. Thus, v-rel may interfere with the normal transcriptional machinery of the cell by acting as a dominant negative mutant. Images PMID:2023921

  20. Electron density and electron temperature measurement in a bi-Maxwellian electron distribution using a derivative method of Langmuir probes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Choi, Ikjin; Chung, ChinWook; Youn Moon, Se

    2013-08-15

    In plasma diagnostics with a single Langmuir probe, the electron temperature T{sub e} is usually obtained from the slope of the logarithm of the electron current or from the electron energy probability functions of current (I)-voltage (V) curve. Recently, Chen [F. F. Chen, Phys. Plasmas 8, 3029 (2001)] suggested a derivative analysis method to obtain T{sub e} by the ratio between the probe current and the derivative of the probe current at a plasma potential where the ion current becomes zero. Based on this method, electron temperatures and electron densities were measured and compared with those from the electron energymore » distribution function (EEDF) measurement in Maxwellian and bi-Maxwellian electron distribution conditions. In a bi-Maxwellian electron distribution, we found the electron temperature T{sub e} obtained from the method is always lower than the effective temperatures T{sub eff} derived from EEDFs. The theoretical analysis for this is presented.« less

  1. Energy spectra of plasma sheet ions and electrons from about 50 eV/e to about 1 MeV during plamsa temperature transitions

    NASA Technical Reports Server (NTRS)

    Christon, S. P.; Mitchell, D. G.; Williams, D. J.; Frank, L. A.; Huang, C. Y.; Eastman, T. E.

    1988-01-01

    ISEE-1 charged-particle measurements obtained during eight plasma temperature transitions (PTTs) in 1978-1979 are compiled in tables and graphs and analyzed in detail, comparing the ion and electron differential energy spectra with the predictions of theoretical models. PTTs are defined as approximately 1-h periods of low bulk plasma velocity and steadily increasing or decreasing thermal energy. A Maxwellian distribution is found to be inadequate in describing the PTT energy spectra, but velocity-exponential and kappa distributions are both successful, the latter especially at higher energies. The power-law index kappa varies from PTT to PTT, but the high-energy spectral index and overall shape of the distribution remain constant during a PTT; both spatial and temporal effects are observed.

  2. Electron distribution functions in electric field environments

    NASA Technical Reports Server (NTRS)

    Rudolph, Terence H.

    1991-01-01

    The amount of current carried by an electric discharge in its early stages of growth is strongly dependent on its geometrical shape. Discharges with a large number of branches, each funnelling current to a common stem, tend to carry more current than those with fewer branches. The fractal character of typical discharges was simulated using stochastic models based on solutions of the Laplace equation. Extension of these models requires the use of electron distribution functions to describe the behavior of electrons in the undisturbed medium ahead of the discharge. These electrons, interacting with the electric field, determine the propagation of branches in the discharge and the way in which further branching occurs. The first phase in the extension of the referenced models , the calculation of simple electron distribution functions in an air/electric field medium, is discussed. Two techniques are investigated: (1) the solution of the Boltzmann equation in homogeneous, steady state environments, and (2) the use of Monte Carlo simulations. Distribution functions calculated from both techniques are illustrated. Advantages and disadvantages of each technique are discussed.

  3. Electron Impact Multiple Ionization Cross Sections for Solar Physics

    NASA Astrophysics Data System (ADS)

    Hahn, M.; Savin, D. W.; Mueller, A.

    2017-12-01

    We have compiled a set of electron-impact multiple ionization (EIMI) cross sections for astrophysically relevant ions. EIMI can have a significant effect on the ionization balance of non-equilibrium plasmas. For example, it can be important if there is a rapid change in the electron temperature, as in solar flares or in nanoflare coronal heating. EIMI is also likely to be significant when the electron energy distribution is non-thermal, such as if the electrons follow a kappa distribution. Cross sections for EIMI are needed in order to account for these processes in plasma modeling and for spectroscopic interpretation. Here, we describe our comparison of proposed semiempirical formulae to the available experimental EIMI cross section data. Based on this comparison, we have interpolated and extrapolated fitting parameters to systems that have not yet been measured. A tabulation of the fit parameters is provided for thousands of EIMI cross sections. We also highlight some outstanding issues that remain to be resolved.

  4. Bis(acesulfamato-kappaO4)diaquabis(3-methylpyridine-kappaN)nickel(II).

    PubMed

    Dege, Necmi; Içbudak, Hasan; Adiyaman, Elif

    2007-01-01

    In the crystal structure of the title compound [systematic name: diaquabis(6-methyl-2,2-dioxo-1,2,3-oxathiazin-4-olato-kappaO4)bis(3-methylpyridine-kappaN)nickel(II)], [Ni(C4H4NO4S)2(C6H7N)2(H2O)2], the Ni(II) centre resides on a centre of symmetry and has a distorted octahedral geometry. The basal plane is formed by two carbonyl O atoms of two monodentate trans-oriented acesulfamate ligands and two trans aqua ligands. The axial positions in the octahedron are occupied by two N atoms of two trans pyridine ligands. Molecules are stacked in columns running along the a axis. There are pi-pi stacking interactions between the molecules in each column, with a distance of 3.623 (2) A between the centroids of the pyridine rings. There are also O-H...O interactions between the columns.

  5. Angular distribution of electrons from powerful accelerators

    NASA Astrophysics Data System (ADS)

    Stepovik, A. P.; Lartsev, V. D.; Blinov, V. S.

    2007-07-01

    A technique for measuring the angular distribution of electrons escaping from the center of the window of the IGUR-3 and ÉMIR-M powerful accelerators (designed at the All-Russia Institute of Technical Physics, Russian Federal Nuclear Center) into ambient air is presented, and measurement data are reported. The number of electrons is measured with cable detectors (the solid angle of the collimator of the detector is ≈0.01 sr). The measurements are made in three azimuthal directions in 120° intervals in the polar angle range 0 22°. The angular distributions of the electrons coming out of the accelerators are represented in the form of B splines.

  6. Nuclear factor kappa B: a potential target for anti-HIV chemotherapy.

    PubMed

    Pande, V; Ramos, M J

    2003-08-01

    The Nuclear Factor Kappa B (NF-kappaB) is a lymphoid-specific transcription factor, which is sequestered in the cytoplasm by the protein IkappaB. NF-kappaB plays a major role in the regulation of HIV-1 gene expression. Upon activation, NF-kappaB is released from IkappaB, moves to the nucleus, and binds to its sites on the HIV long terminal repeat to start transcription of integrated HIV genome. The present review focuses on the NF-kappaB as a potential target for the development of chemotherapy against HIV-1. Beginning from the viral-binding to reverse transcription, integration, and gene expression, to the virion maturation, the life cycle of HIV presents drug-targets at all the stages. As a result, many drugs have been developed and have entered clinical trials. Some of the most important of these are reverse transcriptase and protease inhibitors, which have been used mostly in clinical studies in the form of combined therapy. But, this combined therapy has presented the problem of resistance, due to mutations in the virus. However, targeting NF-kappaB for the suppression of virus does not present the problem of resistance, as NF-kappaB is a normal part of the human T-4 cell, and is not subject to mutations, as is the virus. An overview of the NF-kappaB system and its role in HIV-1 is presented, followed by a critical review of its current and potential synthetic inhibitors. The drugs studied against NF-kappaB fall mainly into three categories: (1) Antioxidants, against oxidative stress conditions, which aid in NF-kappaB activation, (2) IkappaB phosphorylation and degradation inhibitors (the phosphorylation and degradation of IkappaB is necessary to make NF-kappaB free and move to the nucleus), and (3) NF-kappaB DNA binding inhibitors. The antioxidants include N-Acetyl-L-cysteine (NAC), alpha-Lipoic acid, glutathione monoester, pyrrolidine dithiocarbamate, and tepoxalin, of which NAC is the best studied. The IkappaB phosphorylation and degradation inhibitors

  7. Involvement of nuclear factor {kappa}B in platelet CD40 signaling

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hachem, Ahmed; Yacoub, Daniel; Centre Hospitalier Universite de Montreal, 264 boul. Rene-Levesque est, Montreal, Quebec, Canada H2X 1P1

    Highlights: Black-Right-Pointing-Pointer sCD40L induces TRAF2 association to CD40 and NF-{kappa}B activation in platelets. Black-Right-Pointing-Pointer I{kappa}B{alpha} phosphorylation downstream of CD40L/CD40 signaling is independent of p38 MAPK phosphorylation. Black-Right-Pointing-Pointer I{kappa}B{alpha} is required for sCD40L-induced platelet activation and potentiation of aggregation. -- Abstract: CD40 ligand (CD40L) is a thrombo-inflammatory molecule that predicts cardiovascular events. Platelets constitute the major source of soluble CD40L (sCD40L), which has been shown to potentiate platelet activation and aggregation, in a CD40-dependent manner, via p38 mitogen activated protein kinase (MAPK) and Rac1 signaling. In many cells, the CD40L/CD40 dyad also induces activation of nuclear factor kappa B (NF-{kappa}B). Givenmore » that platelets contain NF-{kappa}B, we hypothesized that it may be involved in platelet CD40 signaling and function. In human platelets, sCD40L induces association of CD40 with its adaptor protein the tumor necrosis factor receptor associated factor 2 and triggers phosphorylation of I{kappa}B{alpha}, which are abolished by CD40L blockade. Inhibition of I{kappa}B{alpha} phosphorylation reverses sCD40L-induced I{kappa}B{alpha} phosphorylation without affecting p38 MAPK phosphorylation. On the other hand, inhibition of p38 MAPK phosphorylation has no effect on I{kappa}B{alpha} phosphorylation, indicating a divergence in the signaling pathway originating from CD40 upon its ligation. In functional studies, inhibition of I{kappa}B{alpha} phosphorylation reverses sCD40L-induced platelet activation and potentiation of platelet aggregation in response to a sub-threshold concentration of collagen. This study demonstrates that the sCD40L/CD40 axis triggers NF-{kappa}B activation in platelets. This signaling pathway plays a critical role in platelet activation and aggregation upon sCD40L stimulation and may represent an important target against

  8. Direct covalent modification as a strategy to inhibit nuclear factor-kappa B.

    PubMed

    Pande, Vineet; Sousa, Sérgio F; Ramos, Maria João

    2009-01-01

    Nuclear Factor-KkappaB (NF-kappaB) is a transcription factor whose inappropriate activation may result in the development of a number of diseases including cancer, inflammation, neurodegeneration and AIDS. Recent studies on NF-kappaB mediated pathologies, made therapeutic interventions leading to its inhibition an emerging theme in pharmaceutical research. NF-kappaB resides in the cytoplasm and is activated by several time-dependent factors, leading to proteasome-dependent degradation of its inhibitory protein (IkappaB), resulting in free NF-kappaB (p50 and p65 subunits, involved in disease states), which binds to target DNA sites, further resulting in enhanced transcription of several disease associated proteins. The complex pathway of NF-kappaB, finally leading to its DNA binding, has attracted several approaches interfering with this pathway. One such approach is that of a direct covalent modification of NF-kappaB. In this article, we present a critical review on the pharmacological agents that have been studied as inhibitors of NF-kappaB by covalently modifying redox-regulated cysteine residues in its subunits, ultimately resulting in the inhibition of kappaB DNA recognition and binding. Beginning with a general overview of NF-kappaB pathway and several possibilities of chemical interventions, the significance of redox-regulation in NF-kappaB activation and DNA binding is presented. Further, protein S-thiolation, S-nitrosylation and irreversible covalent modification are described as regular biochemical events in the cell, having provided a guideline for the development of NF-kappaB inhibitors discussed further. Although just a handful of inhibitors, with most of them being alkylating agents have been studied in the present context, this approach presents potential for the development of a new class of NF-kappaB-inhibitors.

  9. Electron velocity distributions near the earth's bow shock

    NASA Technical Reports Server (NTRS)

    Feldman, W. C.; Anderson, R. C.; Bame, S. J.; Gary, S. P.; Gosling, J. T.; Mccomas, D. J.; Thomsen, M. F.; Paschmann, G.; Hoppe, M. M.

    1983-01-01

    New information is presented on the general characteristics of electron distribution functions upstream, within, and downstream of the earth's bow shock, thereby providing new insights into the instabilities in collisionless shocks. The results presented are from a survey of electron velocity distributions measured near the earth's bow shock between October 1977 and December 1978 using the Los Alamos/Garching plasma instrumentation aboard ISEE 2. A wide variety of distribution shapes is found within the different plasma regions in close proximity to the bow shock. It is found that these shapes can be classified into general types that are characteristic of three different plasma regions, namely the upstream region or electron foreshock, the shock proper where most of the heating occurs, and the downstream region or the magnetosheath. Evidence is provided that field-aligned, rather than cross-field, instabilities are the major source of electron dissipation in the earth's bow shock.

  10. Wave-driven butterfly distribution of Van Allen belt relativistic electrons.

    PubMed

    Xiao, Fuliang; Yang, Chang; Su, Zhenpeng; Zhou, Qinghua; He, Zhaoguo; He, Yihua; Baker, D N; Spence, H E; Funsten, H O; Blake, J B

    2015-10-05

    Van Allen radiation belts consist of relativistic electrons trapped by Earth's magnetic field. Trapped electrons often drift azimuthally around Earth and display a butterfly pitch angle distribution of a minimum at 90° further out than geostationary orbit. This is usually attributed to drift shell splitting resulting from day-night asymmetry in Earth's magnetic field. However, direct observation of a butterfly distribution well inside of geostationary orbit and the origin of this phenomenon have not been provided so far. Here we report high-resolution observation that a unusual butterfly pitch angle distribution of relativistic electrons occurred within 5 Earth radii during the 28 June 2013 geomagnetic storm. Simulation results show that combined acceleration by chorus and magnetosonic waves can successfully explain the electron flux evolution both in the energy and butterfly pitch angle distribution. The current provides a great support for the mechanism of wave-driven butterfly distribution of relativistic electrons.

  11. Electron-beam-charged dielectrics: Internal charge distribution

    NASA Technical Reports Server (NTRS)

    Beers, B. L.; Pine, V. W.

    1981-01-01

    Theoretical calculations of an electron transport model of the charging of dielectrics due to electron bombardment are compared to measurements of internal charge distributions. The emphasis is on the distribution of Teflon. The position of the charge centroid as a function of time is not monotonic. It first moves deeper into the material and then moves back near to the surface. In most time regimes of interest, the charge distribution is not unimodal, but instead has two peaks. The location of the centroid near saturation is a function of the incident current density. While the qualitative comparison of theory and experiment are reasonable, quantitative comparison shows discrepancies of as much as a factor of two.

  12. Wave-driven butterfly distribution of Van Allen belt relativistic electrons

    DOE PAGES

    Xiao, Fuliang; Yang, Chang; Su, Zhenpeng; ...

    2015-10-05

    Van Allen radiation belts consist of relativistic electrons trapped by Earth's magnetic field. Trapped electrons often drift azimuthally around Earth and display a butterfly pitch angle distribution of a minimum at 90° further out than geostationary orbit. This is usually attributed to drift shell splitting resulting from day–night asymmetry in Earth’s magnetic field. However, direct observation of a butterfly distribution well inside of geostationary orbit and the origin of this phenomenon have not been provided so far. Here we report high-resolution observation that a unusual butterfly pitch angle distribution of relativistic electrons occurred within 5 Earth radii during the 28more » June 2013 geomagnetic storm. In conclusion, simulation results show that combined acceleration by chorus and magnetosonic waves can successfully explain the electron flux evolution both in the energy and butterfly pitch angle distribution. Finally, the current provides a great support for the mechanism of wave-driven butterfly distribution of relativistic electrons.« less

  13. Wave-driven butterfly distribution of Van Allen belt relativistic electrons

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Xiao, Fuliang; Yang, Chang; Su, Zhenpeng

    Van Allen radiation belts consist of relativistic electrons trapped by Earth's magnetic field. Trapped electrons often drift azimuthally around Earth and display a butterfly pitch angle distribution of a minimum at 90° further out than geostationary orbit. This is usually attributed to drift shell splitting resulting from day–night asymmetry in Earth’s magnetic field. However, direct observation of a butterfly distribution well inside of geostationary orbit and the origin of this phenomenon have not been provided so far. Here we report high-resolution observation that a unusual butterfly pitch angle distribution of relativistic electrons occurred within 5 Earth radii during the 28more » June 2013 geomagnetic storm. In conclusion, simulation results show that combined acceleration by chorus and magnetosonic waves can successfully explain the electron flux evolution both in the energy and butterfly pitch angle distribution. Finally, the current provides a great support for the mechanism of wave-driven butterfly distribution of relativistic electrons.« less

  14. Pre-folding IkappaBalpha alters control of NF-kappaB signaling.

    PubMed

    Truhlar, Stephanie M E; Mathes, Erika; Cervantes, Carla F; Ghosh, Gourisankar; Komives, Elizabeth A

    2008-06-27

    Transcription complex components frequently show coupled folding and binding but the functional significance of this mode of molecular recognition is unclear. IkappaBalpha binds to and inhibits the transcriptional activity of NF-kappaB via its ankyrin repeat (AR) domain. The beta-hairpins in ARs 5-6 in IkappaBalpha are weakly-folded in the free protein, and their folding is coupled to NF-kappaB binding. Here, we show that introduction of two stabilizing mutations in IkappaBalpha AR 6 causes ARs 5-6 to fold cooperatively to a conformation similar to that in NF-kappaB-bound IkappaBalpha. Free IkappaBalpha is degraded by a proteasome-dependent but ubiquitin-independent mechanism, and this process is slower for the pre-folded mutants both in vitro and in cells. Interestingly, the pre-folded mutants bind NF-kappaB more weakly, as shown by both surface plasmon resonance and isothermal titration calorimetry in vitro and immunoprecipitation experiments from cells. One consequence of the weaker binding is that resting cells containing these mutants show incomplete inhibition of NF-kappaB activation; they have significant amounts of nuclear NF-kappaB. Additionally, the weaker binding combined with the slower rate of degradation of the free protein results in reduced levels of nuclear NF-kappaB upon stimulation. These data demonstrate clearly that the coupled folding and binding of IkappaBalpha is critical for its precise control of NF-kappaB transcriptional activity.

  15. Synergistic activation of NF-{kappa}B by nontypeable H. influenzae and S. pneumoniae is mediated by CK2, IKK{beta}-I{kappa}B{alpha}, and p38 MAPK

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kweon, Soo-Mi; Wang, Beinan; Rixter, Davida

    2006-12-15

    In review of the past studies on NF-{kappa}B regulation, most of them have focused on investigating how NF-{kappa}B is activated by a single inducer at a time. Given the fact that, in mixed bacterial infections in vivo, multiple inflammation inducers, including both nontypeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae, are present simultaneously, a key issue that has yet to be addressed is whether NTHi and S. pneumoniae simultaneously activate NF-{kappa}B and the subsequent inflammatory response in a synergistic manner. Here, we show that NTHi and S. pneumoniae synergistically induce NF-{kappa}B-dependent inflammatory response via activation of multiple signaling pathways in vitromore » and in vivo. The classical IKK{beta}-I{kappa}B{alpha} and p38 MAPK pathways are involved in synergistic activation of NF-{kappa}B via two distinct mechanisms, p65 nuclear translocation-dependent and -independent mechanisms. Moreover, casein kinase 2 (CK2) is involved in synergistic induction of NF-{kappa}B via a mechanism dependent on phosphorylation of p65 at both Ser536 and Ser276 sites. These studies bring new insights into the molecular mechanisms underlying the NF-{kappa}B-dependent inflammatory response in polymicrobial infections and may lead to development of novel therapeutic strategies for modulating inflammation in mixed infections for patients with otitis media and chronic obstructive pulmonary diseases.« less

  16. Antenna with distributed strip and integrated electronic components

    DOEpatents

    Rodenbeck, Christopher T [Albuquerque, NM; Payne, Jason A [Albuquerque, NM; Ottesen, Cory W [Albuquerque, NM

    2008-08-05

    An antenna comprises electrical conductors arranged to form a radiating element including a folded line configuration and a distributed strip configuration, where the radiating element can be in proximity to a ground conductor and/or arranged as a dipole. Embodiments of the antenna include conductor patterns formed on a printed wiring board, having a ground plane, spacedly adjacent to and coplanar with the radiating element. An antenna can comprise a distributed strip patterned on a printed wiring board, integrated with electronic components mounted on top of or below the distributed strip, and substantially within the extents of the distributed strip. Mounting of electronic components on top of or below the distributed strip has little effect on the performance of the antenna, and allows for realizing the combination of the antenna and integrated components in a compact form. An embodiment of the invention comprises an antenna including a distributed strip, integrated with a battery mounted on the distributed strip.

  17. The Electron Temperature and Anisotropy in the Solar Wind. Comparison of the Core and Halo Populations

    NASA Astrophysics Data System (ADS)

    Pierrard, V.; Lazar, M.; Poedts, S.; Štverák, Š.; Maksimovic, M.; Trávníček, P. M.

    2016-08-01

    Estimating the temperature of solar wind particles and their anisotropies is particularly important for understanding the origin of their deviations from thermal equilibrium and the effects this has. In the absence of energetic events, the velocity distribution of electrons reveals a dual structure with a thermal (Maxwellian) core and a suprathermal (kappa) halo. This article presents a detailed observational analysis of these two components, providing estimations of their temperatures and temperature anisotropies, and decoding any potential interdependence that their properties may indicate. The dataset used in this study includes more than 120 000 of the distributions measured by three missions in the ecliptic within an extended range of heliocentric distances from 0.3 to over 4 AU. The core temperature is found to decrease with the radial distance, while the halo temperature slightly increases, clarifying an apparent contradiction in previous observational analyses and providing valuable clues about the temperature of the kappa-distributed populations. For low values of the power-index kappa, these two components manifest a clear tendency to deviate from isotropy in the same direction, which seems to confirm the existence of mechanisms with similar effects on both components, e.g., the solar wind expansion, or the particle heating by the fluctuations. However, the existence of plasma states with anticorrelated anisotropies of the core and halo populations and the increase in their number for high values of the power-index kappa suggest a dynamic interplay of these components, mediated, most probably, by the anisotropy-driven instabilities.

  18. Effect of excess superthermal hot electrons on finite amplitude ion-acoustic solitons and supersolitons in a magnetized auroral plasma

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rufai, O. R., E-mail: rrufai@csir.co.za; Bharuthram, R., E-mail: rbharuthram@uwc.ac.za; Singh, S. V., E-mail: satyavir@iigs.iigm.res.in

    2015-10-15

    The effect of excess superthermal electrons is investigated on finite amplitude nonlinear ion-acoustic waves in a magnetized auroral plasma. The plasma model consists of a cold ion fluid, Boltzmann distribution of cool electrons, and kappa distributed hot electron species. The model predicts the evolution of negative potential solitons and supersolitons at subsonic Mach numbers region, whereas, in the case of Cairn's nonthermal distribution model for the hot electron species studied earlier, they can exist both in the subsonic and supersonic Mach number regimes. For the dayside auroral parameters, the model generates the super-acoustic electric field amplitude, speed, width, and pulsemore » duration of about 18 mV/m, 25.4 km/s, 663 m, and 26 ms, respectively, which is in the range of the Viking spacecraft measurements.« less

  19. IBS FOR ION DISTRIBUTION UNDER ELECTRON COOLING.

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    FEDOTOV,A.V.; BEN-ZVI,I.; EIDELMAN, YU.

    Standard models of the intra-beam scattering (IBS) are based on the growth of the rms beam parameters for a Gaussian distribution. As a result of electron cooling, the core of beam distribution is cooled much faster than the tails, producing a denser core. In this paper, we compare various approaches to IBS treatment for such distribution. Its impact on the luminosity is also discussed.

  20. The relationship between kappa and temperature in energetic ion spectra at Jupiter

    NASA Technical Reports Server (NTRS)

    Collier, Michael R.; Hamilton, D. C.

    1995-01-01

    A universal energy per charge kappa function fit is simultaneously applied to the spectra of Voyager 2 Low Energy Charged Particle (LECP) proton, helium, oxygen, sulfur, and carbon ions during 33 Jovian plasma sheet crossings from 26 to 160 R(sub J). The fits yield an approximately linear relationship between high energy spectral index, kappa, and core proton temperature of the form kappa (T(sub H)) approximately = eta dot T(sub H) + kappa(sub 0) with eta = 0.080 ke/V, kappa(sub 0) = 2.86, and T(sub H) measured in keV. Core proton temperatures range from 5 to 35 keV with spectral indices ranging from 3 to 6.

  1. Phi Delta Kappa Viewpoint.

    ERIC Educational Resources Information Center

    Phi Delta Kappa, Trenton, NJ. Trenton Area Chapter.

    This collection of articles on aspects of educational research, service, and leadership, are all written by members the Trenton (New Jersey) Area Chapter of Phi Delta Kappa. "Extra Year Programs: The K-1 Transition," by Richard Graja, reports on a study of 210 families regarding the Extra Year program, an opportunity for children to…

  2. SOLARMAX/Electron Pitch Angle Anisotropy Distributions

    NASA Technical Reports Server (NTRS)

    McKenzie, David L.; Anderson, Phillip C.

    2002-01-01

    This final research report summarizes the scientific work performed by The Aerospace Corporation on SOLARMAX/Electron Pitch Angle Anisotropy Distributions. The period of performance was from June 1, 2000 to December 31, 2001.

  3. Electron energy distributions measured during electron beam/plasma interactions. [in E region

    NASA Technical Reports Server (NTRS)

    Jost, R. J.; Anderson, H. R.; Mcgarity, J. O.

    1980-01-01

    In the large vacuum facility at the NASA-Johnson Space Center an electron beam was projected 20 m parallel to B from a gun with variable accelerating potential (1.0 to 2.5 kV) to an aluminum target. The ionospheric neutral pressure and field were approximated. Beam electron energy distributions were measured directly using an electrostatic deflection analyzer and indirectly with a detector that responded to the X-rays produced by electron impact on the target. At low currents the distribution is sharply peaked at the acceleration potential. At high currents a beam plasma discharge occurs and electrons are redistributed in energy so that the former energy peak broadens to 10-15 percent FWHM with a strongly enhanced low energy tail. At the 10% of maximum point the energy spectrum ranges from less than 1/2 to 1.2 times the gun energy. The effect is qualitatively the same at all pitch angles and locations sampled.

  4. Electron and ion Bernstein waves in Saturnian Magnetosphere

    NASA Astrophysics Data System (ADS)

    Bashir, M. F.; Waheed, A.; Ilie, R.; Naeem, I.; Maqsood, U.; Yoon, P. H.

    2017-12-01

    The study of Bernstein mode is presented in order to interpret the observed micro-structures (MIS) and banded emission (BEM) in the Saturnian magnetosphere. The general dispersion relation of Bernstein wave is derived using the Lerche-NewBerger sum rule for the kappa distribution function and further analyzed the both electron Bernstein (EB) and ion Bernstein (IB) waves. The observational data of particle measurements is obtained from the electron spectrometer (ELS) and the ion mass spectrometer (IMS), which are part of the Cassini Plasma Spectrometer (CAPS) instrument suite on board the Cassini spacecraft. For additional electron data, the measurements of Low Energy Magnetospheric Measurements System of the Magnetospheric Imaging Instrument (LEMMS /MIMI) are also utilized. The effect of kappa spectral index, density ratio (nohe/noce for EB and nohe/noi for IB) and the temperature ratio (The/Tce for EB and The/T(h,c)i for IB) on the dispersion properties are discussed employing the exact numerical analysis to explain the appearing of additional maxima/minima (points where the perpendicular group velocity vanishes, i.e., ∂w/∂k = 0) above/below the lower (for IB) and upper hybrid (EB) bands in the observation and their relation to the MIS and BED. The results of these waves may also be compared with the simulation results of Space Weather Modeling Framework (SWMF) .

  5. Oxidized ultrashort nanotubes as carbon scaffolds for the construction of cell-penetrating NF-kappaB decoy molecules.

    PubMed

    Crinelli, Rita; Carloni, Elisa; Menotta, Michele; Giacomini, Elisa; Bianchi, Marzia; Ambrosi, Gianluca; Giorgi, Luca; Magnani, Mauro

    2010-05-25

    Oligonucleotide (ODN) decoys are synthetic ODNs containing the DNA binding sequence of a transcription factor. When delivered to cells, these molecules can compete with endogenous sequences for binding the transcription factor, thus inhibiting its ability to activate the expression of target genes. Modulation of gene expression by decoy ODNs against nuclear factor-kappaB (NF-kappaB), a transcription factor regulating many genes involved in immunity, has been achieved in a variety of immune/inflammatory disorders. However, the successful use of transcription factor decoys depends on an efficient means to bring the synthetic DNA to target cells. It is known that single-walled carbon nanotubes (SWCNTs), under certain conditions, are able to cross the cell membrane. Thus, we have evaluated the possibility to functionalize SWCNTs with decoy ODNs against NF-kappaB in order to improve their intracellular delivery. To couple ODNs to CNTs, we have exploited the carbodiimide chemistry which allows covalent binding of amino-modified ODNs to carboxyl groups introduced onto SWCNTs through oxidation. The effective binding of ODNs to nanotubes has been demonstrated by a combination of microscopic, spectroscopic, and electrophoretic techniques. The uptake and subcellular distribution of ODN decoys bound to SWCNTs was analyzed by fluorescence microscopy. ODNs were internalized into macrophages and accumulated in the cytosol. Moreover, no cytotoxicity associated with SWCNT administration was observed. Finally, NF-kappaB-dependent gene expression was significantly reduced in cells receiving nanomolar concentrations of SWCNT-NF-kappaB decoys compared to cells receiving SWCNTs or SWCNTs functionalized with a nonspecific ODN sequence, demonstrating both efficacy and specificity of the approach.

  6. 40 CFR 721.10688 - Copper, chloro[tris(2-chloroethyl) phosphite-.kappa.P]-.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...) phosphite-.kappa.P]-. 721.10688 Section 721.10688 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.10688 Copper, chloro[tris(2-chloroethyl) phosphite-.kappa.P]-. (a... copper, chloro[tris(2-chloroethyl) phosphite-.kappa.P]- (PMN P-13-221; CAS No. 24484-01-3) is subject to...

  7. TRIM45 negatively regulates NF-{kappa}B-mediated transcription and suppresses cell proliferation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Shibata, Mio; Sato, Tomonobu; Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638

    2012-06-22

    Highlights: Black-Right-Pointing-Pointer NF-{kappa}B plays an important role in cell survival and carcinogenesis. Black-Right-Pointing-Pointer TRIM45 negatively regulates TNF{alpha}-induced NF-{kappa}B-mediated transcription. Black-Right-Pointing-Pointer TRIM45 overexpression suppresses cell growth. Black-Right-Pointing-Pointer TRIM45 acts as a repressor for the NF-{kappa}B signal and regulates cell growth. -- Abstract: The NF-{kappa}B signaling pathway plays an important role in cell survival, immunity, inflammation, carcinogenesis, and organogenesis. Activation of NF-{kappa}B is regulated by several posttranslational modifications including phosphorylation, neddylation and ubiquitination. The NF-{kappa}B signaling pathway is activated by two distinct signaling mechanisms and is strictly modulated by the ubiquitin-proteasome system. It has been reported that overexpression of TRIM45, one ofmore » the TRIM family ubiquitin ligases, suppresses transcriptional activities of Elk-1 and AP-1, which are targets of the MAPK signaling pathway. In this study, we showed that TRIM45 also negatively regulates TNF{alpha}-induced NF-{kappa}B-mediated transcription by a luciferase reporter assay and that TRIM45 lacking a RING domain also has an activity to inhibit the NF-{kappa}B signal. Moreover, we found that TRIM45 overexpression suppresses cell growth. These findings suggest that TRIM45 acts as a repressor for the NF-{kappa}B signal and regulates cell growth.« less

  8. Dynamic behavior of ion acoustic waves in electron-positron-ion magnetoplasmas with superthermal electrons and positrons

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Saha, Asit, E-mail: asit-saha123@rediffmail.com, E-mail: prasantachatterjee1@rediffmail.com; Department of Mathematics, Siksha Bhavana, Visva Bharati University, Santiniketan-731235; Pal, Nikhil

    The dynamic behavior of ion acoustic waves in electron-positron-ion magnetoplasmas with superthermal electrons and positrons has been investigated in the framework of perturbed and non-perturbed Kadomtsev-Petviashili (KP) equations. Applying the reductive perturbation technique, we have derived the KP equation in electron-positron-ion magnetoplasma with kappa distributed electrons and positrons. Bifurcations of ion acoustic traveling waves of the KP equation are presented. Using the bifurcation theory of planar dynamical systems, the existence of the solitary wave solutions and the periodic traveling wave solutions has been established. Two exact solutions of these waves have been derived depending on the system parameters. Then, usingmore » the Hirota's direct method, we have obtained two-soliton and three-soliton solutions of the KP equation. The effect of the spectral index κ on propagations of the two-soliton and the three-soliton has been shown. Considering an external periodic perturbation, we have presented the quasi periodic behavior of ion acoustic waves in electron-positron-ion magnetoplasmas.« less

  9. Subset of Kappa and Lambda Germline Sequences Result in Light Chains with a Higher Molecular Mass Phenotype.

    PubMed

    Barnidge, David R; Lundström, Susanna L; Zhang, Bo; Dasari, Surendra; Murray, David L; Zubarev, Roman A

    2015-12-04

    In our previous work, we showed that electrospray ionization of intact polyclonal kappa and lambda light chains isolated from normal serum generates two distinct, Gaussian-shaped, molecular mass distributions representing the light-chain repertoire. During the analysis of a large (>100) patient sample set, we noticed a low-intensity molecular mass distribution with a mean of approximately 24 250 Da, roughly 800 Da higher than the mean of the typical kappa molecular-mass distribution mean of 23 450 Da. We also observed distinct clones in this region that did not appear to contain any typical post-translational modifications that would account for such a large mass shift. To determine the origin of the high molecular mass clones, we performed de novo bottom-up mass spectrometry on a purified IgM monoclonal light chain that had a calculated molecular mass of 24 275.03 Da. The entire sequence of the monoclonal light chain was determined using multienzyme digestion and de novo sequence-alignment software and was found to belong to the germline allele IGKV2-30. The alignment of kappa germline sequences revealed ten IGKV2 and one IGKV4 sequences that contained additional amino acids in their CDR1 region, creating the high-molecular-mass phenotype. We also performed an alignment of lambda germline sequences, which showed additional amino acids in the CDR2 region, and the FR3 region of functional germline sequences that result in a high-molecular-mass phenotype. The work presented here illustrates the ability of mass spectrometry to provide information on the diversity of light-chain molecular mass phenotypes in circulation, which reflects the germline sequences selected by the immunoglobulin-secreting B-cell population.

  10. Clinical validation of nuclear factor kappa B expression in invasive breast cancer.

    PubMed

    Agrawal, Anil Kumar; Pielka, Ewa; Lipinski, Artur; Jelen, Michal; Kielan, Wojciech; Agrawal, Siddarth

    2018-01-01

    Breast cancer is the most commonly diagnosed cancer in Polish women. The expression of transcription nuclear factor kappa B, a key inducer of inflammatory response promoting carcinogenesis and cancer progression in breast cancer, is not well-established. We assessed the nuclear factor kappa B expression in a total of 119 invasive breast carcinomas and 25 healthy control samples and correlated this expression pattern with several clinical and pathologic parameters including histologic type and grade, tumor size, lymph node status, estrogen receptor status, and progesterone receptor status. The data used for the analysis were derived from medical records. An immunohistochemical analysis of nuclear factor kappa B, estrogen receptor, and progesterone receptor was carried out and evaluation of stainings was performed. The expression of nuclear factor kappa B was significantly higher than that in the corresponding healthy control samples. No statistical difference was demonstrated in nuclear factor kappa B expression in relation to age, menopausal status, lymph node status, tumor size and location, grade and histologic type of tumor, and hormonal status (estrogen receptor and progesterone receptor). Nuclear factor kappa B is significantly overexpressed in invasive breast cancer tissues. Although nuclear factor kappa B status does not correlate with clinicopathological findings, it might provide important additional information on prognosis and become a promising object for targeted therapy.

  11. Electron concentration distribution in a glow discharge in air flow

    NASA Astrophysics Data System (ADS)

    Mukhamedzianov, R. B.; Gaisin, F. M.; Sabitov, R. A.

    1989-04-01

    Electron concentration distributions in a glow discharge in longitudinal and vortex air flows are determined from the attenuation of the electromagnetic wave passing through the plasma using microwave probes. An analysis of the distribution curves obtained indicates that electron concentration decreases in the direction of the anode. This can be explained by charge diffusion toward the chamber walls and electron recombination and sticking within the discharge.

  12. Smad7 mediates inhibition of Saos2 osteosarcoma cell differentiation by NF{kappa}B

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Eliseev, Roman A.; Schwarz, Edward M.; Zuscik, Michael J.

    2006-01-01

    The transcription factor NF{kappa}B is constitutively activated in various tumor cells where it promotes proliferation and represses apoptosis. The bone morphogenetic proteins (BMPs) delay cell proliferation and promote differentiation and apoptosis of bone cells through activation of Smad downstream effectors and via Smad-independent mechanisms. Thus, NF{kappa}B and BMP pathways play opposing roles in regulating osteoblastic cell fate. Here, we show that in osteosarcoma Saos2 osteoblasts, NF{kappa}B regulates the activity of the BMP/Smad signaling. Inhibition of NF{kappa}B by overexpression of mI{kappa}B leads to the induction of osteoblast differentiation. Saos2 cells overexpressing mI{kappa}B (Saos2-mI{kappa}B) exhibit higher expression of osteoblast phenotypic genes suchmore » as alkaline phosphatase, Runx2 and osteocalcin and are more responsive to BMP2 in comparison to wild-type cells (Saos2-wt) or empty vector infected controls (Saos2-EV). Furthermore, BMP-2 signaling and Smad phosphorylation are significantly increased in Saos2-mI{kappa}B cells in comparison to Saos2-EV cells. Inhibition of NF{kappa}B signaling in Saos2-mI{kappa}B cells is associated with decreased expression of the BMP signaling inhibitor Smad7. While gain of Smad7 function in Saos2-mI{kappa}B cells results in inhibition of BMP signaling, anti-sense knockdown of Smad7 in Saos2-EV cells leads to upregulation of BMP signaling. We therefore conclude that in osteosarcoma Saos2 cells, NF{kappa}B represses BMP/Smad signaling and BMP2-induced differentiation through Smad7.« less

  13. NF-kappaB transcription factor is required for inhibitory avoidance long-term memory in mice.

    PubMed

    Freudenthal, Ramiro; Boccia, Mariano M; Acosta, Gabriela B; Blake, Mariano G; Merlo, Emiliano; Baratti, Carlos M; Romano, Arturo

    2005-05-01

    Although it is generally accepted that memory consolidation requires regulation of gene expression, only a few transcription factors (TFs) have been clearly demonstrated to be specifically involved in this process. Increasing research data point to the participation of the Rel/nuclear factor-kappaB (NF-kappaB) family of TFs in memory and neural plasticity. Here we found that two independent inhibitors of NF-kappaB induced memory impairment in the one-trial step-through inhibitory avoidance paradigm in mice: post-training administration of the drug sulfasalazine and 2 h pretraining administration of a double-stranded DNA oligonucleotide containing the NF-kappaB consensus sequence (kappaB decoy). Conversely, one base mutation of the kappaB decoy (mut-kappaB decoy) injection did not affect long-term memory. Accordingly, the kappaB decoy inhibited NF-kappaB in hippocampus 2 h after injection but no inhibition was found with mut-kappaB decoy administration. A temporal course of hippocampal NF-kappaB activity after training was determined. Unexpectedly, an inhibition of NF-kappaB was found 15 min after training in shocked and unshocked groups when compared with the naïve group. Hippocampal NF-kappaB was activated 45 min after training in both shocked and unshocked groups, decreasing 1 h after training and returning to basal levels 2 and 4 h after training. On the basis of the latter results, we propose that activation of NF-kappaB in hippocampus is part of the molecular mechanism involved in the storage of contextual features that constitute the conditioned stimulus representation. The results presented here provide the first evidence to support NF-kappaB activity being regulated in hippocampus during consolidation, stressing the role of this TF as a conserved molecular mechanism for memory storage.

  14. Purinergic signaling is required for fluid shear stress-induced NF-{kappa}B translocation in osteoblasts

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Genetos, Damian C., E-mail: dgenetos@ucdavis.edu; Karin, Norman J.; Geist, Derik J.

    2011-04-01

    Fluid shear stress regulates gene expression in osteoblasts, in part by activation of the transcription factor NF-{kappa}B. We examined whether this process was under the control of purinoceptor activation. MC3T3-E1 osteoblasts under static conditions expressed the NF-{kappa}B inhibitory protein I{kappa}B{alpha} and exhibited cytosolic localization of NF-{kappa}B. Under fluid shear stress, I{kappa}B{alpha} levels decreased, and concomitant nuclear localization of NF-{kappa}B was observed. Cells exposed to fluid shear stress in ATP-depleted medium exhibited no significant reduction in I{kappa}B{alpha}, and NF-{kappa}B remained within the cytosol. Similar results were found using oxidized ATP or Brilliant Blue G, P2X{sub 7} receptor antagonists, indicating that themore » P2X{sub 7} receptor is responsible for fluid shear-stress-induced I{kappa}B{alpha} degradation and nuclear accumulation of NF-{kappa}B. Pharmacologic blockage of the P2Y6 receptor also prevented shear-induced I{kappa}B{alpha} degradation. These phenomena involved neither ERK1/2 signaling nor autocrine activation by P2X{sub 7}-generated lysophosphatidic acid. Our results suggest that fluid shear stress regulates NF-{kappa}B activity through the P2Y{sub 6} and P2X{sub 7} receptor.« less

  15. Measuring agreement of multivariate discrete survival times using a modified weighted kappa coefficient.

    PubMed

    Guo, Ying; Manatunga, Amita K

    2009-03-01

    Assessing agreement is often of interest in clinical studies to evaluate the similarity of measurements produced by different raters or methods on the same subjects. We present a modified weighted kappa coefficient to measure agreement between bivariate discrete survival times. The proposed kappa coefficient accommodates censoring by redistributing the mass of censored observations within the grid where the unobserved events may potentially happen. A generalized modified weighted kappa is proposed for multivariate discrete survival times. We estimate the modified kappa coefficients nonparametrically through a multivariate survival function estimator. The asymptotic properties of the kappa estimators are established and the performance of the estimators are examined through simulation studies of bivariate and trivariate survival times. We illustrate the application of the modified kappa coefficient in the presence of censored observations with data from a prostate cancer study.

  16. Features of Electron Density Distribution in Delafossite Cualo2

    NASA Astrophysics Data System (ADS)

    Pogoreltsev, A. I.; Schmidt, S. V.; Gavrilenko, A. N.; Shulgin, D. A.; Korzun, B. V.; Matukhin, V. L.

    2015-07-01

    We have used pulsed 63,65Cu nuclear quadrupole resonance at room temperature to study the semiconductor compound CuAlO2 with a delafossite crystal structure, and we have determined the quadrupole frequency νQ = 28.12 MHz and the asymmetry parameter η ~ 0, which we used to study the features of the electron density distribution in the vicinity of the quadrupolar nucleus. In order to take into account the influence of correlation effects on the electric field gradient, we carried out ab initio calculations within the density functional theory (DFT) approximation using a set of correlation functionals VWN1RPA, VWN5, PW91LDA, CPW91, and B3LYP1. We mapped the electron density distribution in the vicinity of the quadrupolar copper nucleus for the Cu7Al6o{14/- 1} cluster and we calculated the size of the LUMO-HOMO gap, Δ ~ 3.33 eV. We established the anisotropy of the spatial electron density distribution. Based on analysis of the electron density distribution obtained, we suggest that the bond in CuAlO2 is not purely covalent.

  17. NF-kappaB activation in cancer: a challenge for ubiquitination- and proteasome-based therapeutic approach.

    PubMed

    Amit, Sharon; Ben-Neriah, Yinon

    2003-02-01

    Nuclear factor-kappa B (NF-kappaB) activation relies primarily on ubiquitin-mediated degradation of its inhibitor IkappaB. NF-kappaB plays an important role in many aspects of tumor development, progression, and therapy. Some types of cancer are characterized by constitutive NF-kappaB activity, whereas in others such activity is induced following chemotherapy. NF-kappaB-harboring tumors are generally resistant to chemotherapy and their eradication requires NF-kappaB inhibition. Here we describe the mechanisms of NF-kappaB activation in normal and tumor cells, review prevalent notions regarding the factor's contribution to tumorigenicity and discuss present and future options for NF-kappaB inhibition in cancer. The ubiquitination-mediated activation of NF-kappaB is intersected by another cancer-associated protein, beta-catenin. We, therefore, compare the related activation pathways and discuss the possibility of differential targeting of the involved ubiquitination machinery. Copyright 2002 Elsevier Science Ltd.

  18. The Pseudomonas aeruginosa exopolysaccharide Psl facilitates surface adherence and NF-kappaB activation in A549 cells.

    PubMed

    Byrd, Matthew S; Pang, Bing; Mishra, Meenu; Swords, W Edward; Wozniak, Daniel J

    2010-06-29

    In order for the opportunistic Gram-negative pathogen Pseudomonas aeruginosa to cause an airway infection, the pathogen interacts with epithelial cells and the overlying mucous layer. We examined the contribution of the biofilm polysaccharide Psl to epithelial cell adherence and the impact of Psl on proinflammatory signaling by flagellin. Psl has been implicated in the initial attachment of P. aeruginosa to biotic and abiotic surfaces, but its direct role in pathogenesis has not been evaluated (L. Ma, K. D. Jackson, R. M. Landry, M. R. Parsek, and D. J. Wozniak, J. Bacteriol. 188:8213-8221, 2006). Using an NF-kappaB luciferase reporter system in the human epithelial cell line A549, we show that both Psl and flagellin are necessary for full activation of NF-kappaB and production of the interleukin 8 (IL-8) chemokine. We demonstrate that Psl does not directly stimulate NF-kappaB activity, but indirectly as a result of increasing contact between bacterial cells and epithelial cells, it facilitates flagellin-mediated proinflammatory signaling. We confirm differential adherence of Psl and/or flagellin mutants by scanning electron microscopy and identify Psl-dependent membrane structures that may participate in adherence. Although we hypothesized that Psl would protect P. aeruginosa from recognition by the epithelial cell line A549, we instead observed a positive role for Psl in flagellin-mediated NF-kappaB activation, likely as a result of increasing contact between bacterial cells and epithelial cells.

  19. In vitro anticancer property of a novel thalidomide analogue through inhibition of NF-kappaB activation in HL-60 cells.

    PubMed

    Li, Min; Sun, Wan; Yang, Ya-ping; Xu, Bo; Yi, Wen-yuan; Ma, Yan-xia; Li, Zhong-jun; Cui, Jing-rong

    2009-01-01

    To investigate the anticancer property and possible mechanism of action of a novel sugar-substituted thalidomide derivative (STA-35) on HL-60 cells in vitro. TNF-alpha-induced NF-kappaB activation was determined using a reporter gene assay. The MTT assay was used to measure cytotoxicity of the compound. The appearance of apoptotic Sub-G1 cells was detected by flow cytometry analysis. PARP cleavage and protein expression of NF-kappaB p65 and its inhibitor IkappaB were viewed by Western blotting. TA-35 (1-20 micromol/L) suppressed TNF-alpha-induced NF-kappaB activation in transfected cells (HEK293/pNiFty-SEAP) in a dose- (1-20 micromol/L) and time-dependent (0-48 h) manner. It was also shown that STA-35 exerted a dose-dependent inhibitory effect on HL-60 cell proliferation with an IC(50) value of 9.05 micromol/L. In addition, STA-35 induced apoptosis in HL-60 cells, as indicated by the appearance of a Sub-G1 peak in the cell cycle distribution, as well as poly ADP-ribose polymerase (PARP) cleavage. Subsequently, both NF-kappaB p65 and its inhibitor IkappaB gradually accumulated in cytoplasmic extracts in a dose- and time-dependent manner, indicating the blockage of NF-kappaB translocation induced by TNF-alpha from the cytoplasm to the nucleus. A novel sugar-substituted thalidomide derivative, STA-35, is potent toward HL-60 cells in vitro and induces apoptosis by the suppression of NF-kappaB activation.

  20. Mechanisms for kappa reduction and color removal by xylanases

    Treesearch

    Thomas W. Jeffries; Mark Davis; Brian Rosin; Larry L. Landucci

    1998-01-01

    Xylanases reduce kappa and release UV- and visibly absorptive materials from kraft pulps. The extents of these actions depend on the origin and processing of the pulp, access of enzymes to the substrate, and the natures of the enzymes. Hexeneuronic acid (HexA) is a component of kraft pulp xylans that accounts for a fraction of the kappa content. It absorbs strongly in...

  1. 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…

  2. Kappa statistic to measure agreement beyond chance in free-response assessments.

    PubMed

    Carpentier, Marc; Combescure, Christophe; Merlini, Laura; Perneger, Thomas V

    2017-04-19

    The usual kappa statistic requires that all observations be enumerated. However, in free-response assessments, only positive (or abnormal) findings are notified, but negative (or normal) findings are not. This situation occurs frequently in imaging or other diagnostic studies. We propose here a kappa statistic that is suitable for free-response assessments. We derived the equivalent of Cohen's kappa statistic for two raters under the assumption that the number of possible findings for any given patient is very large, as well as a formula for sampling variance that is applicable to independent observations (for clustered observations, a bootstrap procedure is proposed). The proposed statistic was applied to a real-life dataset, and compared with the common practice of collapsing observations within a finite number of regions of interest. The free-response kappa is computed from the total numbers of discordant (b and c) and concordant positive (d) observations made in all patients, as 2d/(b + c + 2d). In 84 full-body magnetic resonance imaging procedures in children that were evaluated by 2 independent raters, the free-response kappa statistic was 0.820. Aggregation of results within regions of interest resulted in overestimation of agreement beyond chance. The free-response kappa provides an estimate of agreement beyond chance in situations where only positive findings are reported by raters.

  3. Is NF-kappaB a good target for cancer therapy? Hopes and pitfalls.

    PubMed

    Baud, Véronique; Karin, Michael

    2009-01-01

    Nuclear factor kappaB (NF-kappaB) transcription factors have a key role in many physiological processes such as innate and adaptive immune responses, cell proliferation, cell death, and inflammation. It has become clear that aberrant regulation of NF-kappaB and the signalling pathways that control its activity are involved in cancer development and progression, as well as in resistance to chemotherapy and radiotherapy. This article discusses recent evidence from cancer genetics and cancer genome studies that support the involvement of NF-kappaB in human cancer, particularly in multiple myeloma. The therapeutic potential and benefit of targeting NF-kappaB in cancer, and the possible complications and pitfalls of such an approach, are explored.

  4. Auroral electron distribution function

    NASA Technical Reports Server (NTRS)

    Kaufmann, R. L.; Dusenbery, P. B.; Thomas, B. J.; Arnoldy, R. L.

    1978-01-01

    During a rocket flight over an active aurora, electron velocity distribution is studied in the 15-25 keV range. The results are then compared to optical observations made by all-sky cameras and a television system. A broad plateau produced by downcoming electrons was observed. Smaller plateaus were seen when the rocket was south of arcs evident in all-sky camera photographs. By extending to higher energies when the rocket passed out of auroral forms, the plateaus appeared to broaden. When the rocket left an arc or entered weak diffuse auroral structures, the plateaus shrank as the more energetic portions faded. When field-aligned rays were observed within the arcs, the plateau's high-velocity cutoff was found to fluctuate. The results indicate that the auroral plasma was very unstable above the rocket. It is suggested that plateaus are produced as an unstable plasma evolves toward a quasi-equilibrium state.

  5. Nomogram for sample size calculation on a straightforward basis for the kappa statistic.

    PubMed

    Hong, Hyunsook; Choi, Yunhee; Hahn, Seokyung; Park, Sue Kyung; Park, Byung-Joo

    2014-09-01

    Kappa is a widely used measure of agreement. However, it may not be straightforward in some situation such as sample size calculation due to the kappa paradox: high agreement but low kappa. Hence, it seems reasonable in sample size calculation that the level of agreement under a certain marginal prevalence is considered in terms of a simple proportion of agreement rather than a kappa value. Therefore, sample size formulae and nomograms using a simple proportion of agreement rather than a kappa under certain marginal prevalences are proposed. A sample size formula was derived using the kappa statistic under the common correlation model and goodness-of-fit statistic. The nomogram for the sample size formula was developed using SAS 9.3. The sample size formulae using a simple proportion of agreement instead of a kappa statistic and nomograms to eliminate the inconvenience of using a mathematical formula were produced. A nomogram for sample size calculation with a simple proportion of agreement should be useful in the planning stages when the focus of interest is on testing the hypothesis of interobserver agreement involving two raters and nominal outcome measures. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Kappa Cygnids (KCG) by TV observation results

    NASA Astrophysics Data System (ADS)

    Shiba, Yasuo

    2017-12-01

    The kappa Cygnids (KCG) and its nearby region were researched by using Japanese automatic TV observation network (SonotaCo network) results for 2007-2016. KCG in 2007 and 2014 were observed with an enhancement of eight times as many meteors than ordinary years at solar longitude 145 degrees. Also the 2013 KCG were enhanced with three times the number of meteors recorded than ordinary years at solar longitude 135 degrees. In years of observed enhanced KCG (2007, 2013, 2014) luminous magnitudes were brighter than in ordinary years. The 2007 and 2014 KCG radiant distributions were similar but shifted 5 degrees to the north in 2013. The 2013 KCG orbital elements were systematically different from 2007 and 2014. If a continuous meteoroid distribution in the solar system causes the enhanced KCG, it is suggested that a distorted `swarm' has been constructed. The annual KCG radiant distribution and distributions of every orbital element have some peaks which indicate a complex meteor shower. Luminous trajectory altitudes in years of observed enhanced KCG were higher than the annual KCG height. August Draconids (AUD) is an annual meteor shower, many meteors of which are decided to also belong to KCG by using the criterion, but each meteor shower is independent because they have different characteristics. AUD radiants on the celestial sphere drift to the west and form an arc lasting till the end of September. I recommend to create a standard to decide for two meteor showers whether they are truly two meteor showers or not.

  7. Kappa2 opioid receptor subtype binding requires the presence of the DOR-1 gene.

    PubMed

    Ansonoff, Michael A; Wen, Ting; Pintar, John E

    2010-01-01

    Over the past several years substantial evidence has documented that opioid receptor homo- and heterodimers form in cell lines expressing one or more of the opioid receptors. We used opioid receptor knockout mice to determine whether in vivo pharmacological characteristics of kappa1 and kappa2 opioid receptors changed following knockout of specific opioid receptors. Using displacement of the general opioid ligand diprenorphine, we observed that occupancy or knockout of the DOR-1 gene increases the binding density of kappa1 receptors and eliminates kappa2 receptors in crude membrane preparations while the total density of kappa opioid binding sites is unchanged. Further, the analgesic potency of U69,593 in cumulative dose response curves is enhanced in mice lacking the DOR-1 gene. These results demonstrate that the DOR-1 gene is required for the expression of the kappa2 opioid receptor subtype and are consistent with the possibility that a KOR-1/DOR-1 heterodimer mediates kappa2 pharmacology.

  8. Multicomponent plasma expansion into vacuum with non-Maxwellian electrons

    NASA Astrophysics Data System (ADS)

    Elkamash, Ibrahem; Kourakis, Ioannis

    2016-10-01

    The expansion of a collisionless plasma into vacuum has been widely studied since the early works of Gurevich et al and Allen and coworkers. It has received momentum in recent years, in particular in the context of ultraintense laser pulse interaction with a solid target, in an effort to elucidate the generation of high energy ion beams. In most present day experiments, laser produced plasmas contain several ion species, due to increasingly complicated composite targets. Anderson et al have studied the isothermal expansion of a two-ion-species plasma. As in most earlier works, the electrons were assumed to be isothermal throughout the expansion. However, in more realistic situations, the evolution of laser produced plasmas into vacuum is mainly governed by nonthermal electrons. These electrons are characterized by particle distribution functions with high energy tails, which may significantly deviate from the Maxwellian distribution. In this paper, we present a theoretical model for plasma expansion of two component plasma with nonthermal electrons, modelled by a kappa-type distribution. The superthermal effect on the ion density, velocity and the electric field is investigated. It is shown that energetic electrons have a significant effecton the expansion dynamics of the plasma. This work was supported from CPP/QUB funding. One of us (I.S. Elkamash) acknowledges financial support by an Egyptian Government fellowship.

  9. Evolving Nonthermal Electron Distributions in Simulations of Sgr A*

    NASA Astrophysics Data System (ADS)

    Chael, Andrew; Narayan, Ramesh

    2018-01-01

    The accretion flow around Sagittarius A* (Sgr A*), the black hole at the Galactic Center, produces strong variability from the radio to X-rays on timescales of minutes to hours. This rapid, powerful variability is thought to be powered by energetic particle acceleration by plasma processes like magnetic reconnection and shocks. These processes can accelerate particles into non-thermal distributions which do not quickly isothermal in the low densities found around hot accretion flows. Current state-of-the-art simulations of accretion flows around black holes assume either a single-temperature gas or, at best, a two-temperature gas with thermal ions and electrons. We present results from incorporating the self-consistent evolution of a non-thermal electron population in a GRRMHD simulation of Sgr A*. The electron distribution is evolved across space, time, and Lorentz factor in parallel with background thermal ion, electron, and radiation fluids. Energy injection into the non-thermal distribution is modeled with a sub-grid prescription based on results from particle-in-cell simulations of magnetic reconnection. The energy distribution of the non-thermal electrons shows strong variability, and the spectral shape traces the complex interplay between the local viscous heating rate, magnetic field strength, and fluid velocity. Results from these simulations will be used in interpreting forthcoming data from the Event Horizon Telescope that resolves Sgr A*'s sub-mm variability in both time and space.

  10. 40 CFR 721.10356 - Zinc, bis[3-(acetyl-.kappa.O)-6-methyl-2H-pyran-2,4(3H)-dionato-.kappa.O4]diaqua-.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Zinc, bis[3-(acetyl-.kappa.O)-6-methyl-2H-pyran-2,4(3H)-dionato-.kappa.O4]diaqua-. 721.10356 Section 721.10356 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific...

  11. 40 CFR 721.10356 - Zinc, bis[3-(acetyl-.kappa.O)-6-methyl-2H-pyran-2,4(3H)-dionato-.kappa.O4]diaqua-.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Zinc, bis[3-(acetyl-.kappa.O)-6-methyl-2H-pyran-2,4(3H)-dionato-.kappa.O4]diaqua-. 721.10356 Section 721.10356 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific...

  12. 40 CFR 721.10356 - Zinc, bis[3-(acetyl-.kappa.O)-6-methyl-2H-pyran-2,4(3H)-dionato-.kappa.O4]diaqua-.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Zinc, bis[3-(acetyl-.kappa.O)-6-methyl-2H-pyran-2,4(3H)-dionato-.kappa.O4]diaqua-. 721.10356 Section 721.10356 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific...

  13. Salicylates inhibit flavivirus replication independently of blocking nuclear factor kappa B activation.

    PubMed

    Liao, C L; Lin, Y L; Wu, B C; Tsao, C H; Wang, M C; Liu, C I; Huang, Y L; Chen, J H; Wang, J P; Chen, L K

    2001-09-01

    Flaviviruses comprise a positive-sense RNA genome that replicates exclusively in the cytoplasm of infected cells. Whether flaviviruses require an activated nuclear factor(s) to complete their life cycle and trigger apoptosis in infected cells remains elusive. Flavivirus infections quickly activate nuclear factor kappa B (NF-kappaB), and salicylates have been shown to inhibit NF-kappaB activation. In this study, we investigated whether salicylates suppress flavivirus replication and virus-induced apoptosis in cultured cells. In a dose-dependent inhibition, we found salicylates within a range of 1 to 5 mM not only restricted flavivirus replication but also abrogated flavivirus-triggered apoptosis. However, flavivirus replication was not affected by a specific NF-kappaB peptide inhibitor, SN50, and a proteosome inhibitor, lactacystin. Flaviviruses also replicated and triggered apoptosis in cells stably expressing IkappaBalpha-DeltaN, a dominant-negative mutant that antagonizes NF-kappaB activation, as readily as in wild-type BHK-21 cells, suggesting that NF-kappaB activation is not essential for either flavivirus replication or flavivirus-induced apoptosis. Salicylates still diminished flavivirus replication and blocked apoptosis in the same IkappaBalpha-DeltaN cells. This inhibition of flaviviruses by salicylates could be partially reversed by a specific p38 mitogen-activated protein (MAP) kinase inhibitor, SB203580. Together, these results show that the mechanism by which salicylates suppress flavivirus infection may involve p38 MAP kinase activity but is independent of blocking the NF-kappaB pathway.

  14. Shear flow driven tripolar vortices in a nonuniform electron-ion magnetoplasma with non-Maxwellian electrons

    NASA Astrophysics Data System (ADS)

    Masood, W.; Mirza, Arshad M.

    2014-04-01

    A set of nonlinear equations governing the dynamics of finite amplitude drift-ion acoustic-waves is derived for sheared ion flows parallel and perpendicular to the ambient magnetic field in the presence of Cairns and Kappa distributed electrons. It is shown that stationary solution of the nonlinear equations can be represented in the form of a tripolar vortex for specific profiles of the equilibrium sheared flows. The tripolar vortices are, however, observed to form on a scale of the order of ion Larmor radius ρ i which is calculated to be around a Kilometer for the plasma parameters found in the Saturn's E-ring. The relevance of the present investigation in planetary environments is also pointed out.

  15. Mitochondria mediate tumor necrosis factor-alpha/NF-kappaB signaling in skeletal muscle myotubes

    NASA Technical Reports Server (NTRS)

    Li, Y. P.; Atkins, C. M.; Sweatt, J. D.; Reid, M. B.; Hamilton, S. L. (Principal Investigator)

    1999-01-01

    Tumor necrosis factor-alpha (TNF-alpha) is implicated in muscle atrophy and weakness associated with a variety of chronic diseases. Recently, we reported that TNF-alpha directly induces muscle protein degradation in differentiated skeletal muscle myotubes, where it rapidly activates nuclear factor kappaB (NF-kappaB). We also have found that protein loss induced by TNF-alpha is NF-kappaB dependent. In the present study, we analyzed the signaling pathway by which TNF-alpha activates NF-kappaB in myotubes differentiated from C2C12 and rat primary myoblasts. We found that activation of NF-kappaB by TNF-alpha was blocked by rotenone or amytal, inhibitors of complex I of the mitochondrial respiratory chain. On the other hand, antimycin A, an inhibitor of complex III, enhanced TNF-alpha activation of NK-kappaB. These results suggest a key role of mitochondria-derived reactive oxygen species (ROS) in mediating NF-kappaB activation in muscle. In addition, we found that TNF-alpha stimulated protein kinase C (PKC) activity. However, other signal transduction mediators including ceramide, Ca2+, phospholipase A2 (PLA2), and nitric oxide (NO) do not appear to be involved in the activation of NF-kappaB.

  16. Electron Pitch Angle Distributions Along Field Lines Connected to the Auroral Region from 25 to 1.2 RJ Measured by the Jovian Auroral Distributions Experiment-Electrons (JADE-E) on Juno

    NASA Astrophysics Data System (ADS)

    Allegrini, F.; Bagenal, F.; Bolton, S. J.; Bonfond, B.; Chae, K.; Clark, G. B.; Connerney, J. E. P.; Ebert, R. W.; Gladstone, R.; Hue, V.; Hospodarsky, G. B.; Kim, T. K. H.; Kurth, W. S.; Levin, S.; Louarn, P.; Mauk, B.; McComas, D. J.; Pollock, C. J.; Ranquist, D. A.; Reno, M. L.; Saur, J.; Szalay, J.; Thomsen, M. F.; Valek, P. W.; Wilson, R. J.

    2017-12-01

    The Jovian Auroral Distributions Experiment (JADE) on Juno provides critical in situ measurements of electrons and ions needed to understand the plasma distributions and processes that fill the Jovian magnetosphere and ultimately produce Jupiter's bright and dynamic aurora. JADE is an instrument suite that includes two essentially identical electron sensors (JADE-Es) and a single ion sensor (JADE-I). JADE-E measures electron energy distributions from 0.1 to 100 keV and provides detailed electron pitch angle distributions (PAD) at 7.5° resolution. Juno's trajectories in the northern hemisphere have allowed JADE to sample electron energy and pitch angle distributions on field lines connected to the auroral regions from as close as 1.2 RJ all the way to distances greater than 25 RJ. Here, we report on the evolution of these distributions. Specifically, the PADs change from mostly uniform at distances greater than 20 RJ, to butterfly from 18 to 12 RJ, to field aligned or pancake, depending on the energy, closer to Jupiter. Below 1.5 RJ, electron beams and loss cones are observed.

  17. Chronic intermittent hypoxia activates nuclear factor-{kappa}B in cardiovascular tissues in vivo

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Greenberg, Harly; Ye Xiaobing; Wilson, David

    2006-05-05

    Obstructive sleep apnea (OSA) is an important risk factor for cardiovascular morbidity and mortality. The mechanisms through which OSA promotes the development of cardiovascular disease are poorly understood. In this study, we tested the hypotheses that chronic exposure to intermittent hypoxia and reoxygenation (CIH) is a major pathologic factor causing cardiovascular inflammation, and that CIH-induces cardiovascular inflammation and pathology by activating the NF-{kappa}B pathway. We demonstrated that exposure of mice to CIH activated NF-{kappa}B in cardiovascular tissues, and that OSA patients had markedly elevated monocyte NF-{kappa}B activity, which was significantly decreased when obstructive apneas and their resultant CIH were eliminatedmore » by nocturnal CPAP therapy. The elevated NF-{kappa}B activity induced by CIH is accompanied by and temporally correlated to the increased expression of iNOS protein, a putative and important NF-{kappa}B-dependent gene product. Thus, CIH-mediated NF-{kappa}B activation may be a molecular mechanism linking OSA and cardiovascular pathologies seen in OSA patients.« less

  18. Electron distribution function in a plasma generated by fission fragments

    NASA Technical Reports Server (NTRS)

    Hassan, H. A.; Deese, J. E.

    1976-01-01

    A Boltzmann equation formulation is presented for the determination of the electron distribution function in a plasma generated by fission fragments. The formulation takes into consideration ambipolar diffusion, elastic and inelastic collisions, recombination and ionization, and allows for the fact that the primary electrons are not monoenergetic. Calculations for He in a tube coated with fissionable material shows that, over a wide pressure and neutron flux range, the distribution function is non-Maxwellian, but the electrons are essentially thermal. Moreover, about a third of the energy of the primary electrons is transferred into the inelastic levels of He. This fraction of energy transfer is almost independent of pressure and neutron flux.

  19. EWS-FLI1 inhibits TNF{alpha}-induced NF{kappa}B-dependent transcription in Ewing sarcoma cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lagirand-Cantaloube, Julie, E-mail: julie.cantaloube@crbm.cnrs.fr; Laud, Karine, E-mail: karine.laud@curie.fr; Institut Curie, Genetique et biologie des cancers, Paris

    2010-09-03

    Research highlights: {yields} EWS-FLI1 interferes with TNF-induced activation of NF{kappa}B in Ewing sarcoma cells. {yields} EWS-FLI1 knockdown in Ewing sarcoma cells increases TNF-induced NF{kappa}B binding to DNA. {yields} EWS-FLI1 reduces TNF-stimulated NF{kappa}B-dependent transcriptional activation. {yields} Constitutive NF{kappa}B activity is not affected by EWS-FLI1. {yields} EWS-FLI1 physically interacts with NF{kappa}B p65 in vivo. -- Abstract: Ewing sarcoma is primarily caused by a t(11;22) chromosomal translocation encoding the EWS-FLI1 fusion protein. To exert its oncogenic function, EWS-FLI1 acts as an aberrant transcription factor, broadly altering the gene expression profile of tumor cells. Nuclear factor-kappaB (NF{kappa}B) is a tightly regulated transcription factor controllingmore » cell survival, proliferation and differentiation, as well as tumorigenesis. NF{kappa}B activity is very low in unstimulated Ewing sarcoma cells, but can be induced in response to tumor necrosis factor (TNF). We wondered whether NF{kappa}B activity could be modulated by EWS-FLI1 in Ewing sarcoma. Using a knockdown approach in Ewing sarcoma cells, we demonstrated that EWS-FLI1 has no influence on NF{kappa}B basal activity, but impairs TNF-induced NF{kappa}B-driven transcription, at least in part through inhibition of NF{kappa}B binding to DNA. We detected an in vivo physical interaction between the fusion protein and NF{kappa}B p65, which could mediate these effects. Our findings suggest that, besides directly controlling the activity of its primary target promoters, EWS-FLI1 can also indirectly influence gene expression in tumor cells by modulating the activity of key transcription factors such as NF{kappa}B.« less

  20. Electron-impact Multiple-ionization Cross Sections for Atoms and Ions of Helium through Zinc

    NASA Astrophysics Data System (ADS)

    Hahn, M.; Müller, A.; Savin, D. W.

    2017-12-01

    We compiled a set of electron-impact multiple-ionization (EIMI) cross section for astrophysically relevant ions. EIMIs can have a significant effect on the ionization balance of non-equilibrium plasmas. For example, it can be important if there is a rapid change in the electron temperature or if there is a non-thermal electron energy distribution, such as a kappa distribution. Cross section for EIMI are needed in order to account for these processes in plasma modeling and for spectroscopic interpretation. Here, we describe our comparison of proposed semiempirical formulae to available experimental EIMI cross-section data. Based on this comparison, we interpolated and extrapolated fitting parameters to systems that have not yet been measured. A tabulation of the fit parameters is provided for 3466 EIMI cross sections and the associated Maxwellian plasma rate coefficients. We also highlight some outstanding issues that remain to be resolved.

  1. Regulation of NF-{kappa}B activity in astrocytes: effects of flavonoids at dietary-relevant concentrations

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Spilsbury, Alison; Vauzour, David; Spencer, Jeremy P.E.

    Highlights: Black-Right-Pointing-Pointer We tested the hypothesis that low concentrations of flavonoids inhibit NF-{kappa}B in astrocytes. Black-Right-Pointing-Pointer Primary cultured astrocytes possess a functional {kappa}B-system, measured using luciferase assays. Black-Right-Pointing-Pointer Seven flavonoids (100 nM-1 {mu}M) failed to reduce NF-{kappa}B activity in astrocytes. Black-Right-Pointing-Pointer Four flavonoids (100 nM-1 {mu}M) failed to reduce TNFa-stimulated NF-{kappa}B activity in astrocytes. Black-Right-Pointing-Pointer (-)-Epicatechin did not regulate nuclear translocation of the NF-{kappa}B subunit, p65. -- Abstract: Neuroinflammation plays an important role in the progression of neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Sustained activation of nuclear transcription factor {kappa}B (NF-{kappa}B) is thought to play an importantmore » role in the pathogenesis of neurodegenerative disorders. Flavonoids have been shown to possess antioxidant and anti-inflammatory properties and we investigated whether flavonoids, at submicromolar concentrations relevant to their bioavailability from the diet, were able to modulate NF-{kappa}B signalling in astrocytes. Using luciferase reporter assays, we found that tumour necrosis factor (TNF{alpha}, 150 ng/ml) increased NF-{kappa}B-mediated transcription in primary cultures of mouse cortical astrocytes, which was abolished on co-transfection of a dominant-negative I{kappa}B{alpha} construct. In addition, TNF{alpha} increased nuclear localisation of p65 as shown by immunocytochemistry. To investigate potential flavonoid modulation of NF-{kappa}B activity, astrocytes were treated with flavonoids from different classes; flavan-3-ols ((-)-epicatechin and (+)-catechin), flavones (luteolin and chrysin), a flavonol (kaempferol) or the flavanones (naringenin and hesperetin) at dietary-relevant concentrations (0.1-1 {mu}M) for 18 h. None of the flavonoids modulated constitutive or

  2. Transcription factor NF-kappaB participates in regulation of epithelial cell turnover in the colon.

    PubMed

    Inan, M S; Tolmacheva, V; Wang, Q S; Rosenberg, D W; Giardina, C

    2000-12-01

    The transcription factor nuclear factor (NF)-kappaB regulates the expression of genes that can influence cell proliferation and death. Here we analyze the contribution of NF-kappaB to the regulation of epithelial cell turnover in the colon. Immunohistochemical, immunoblot, and DNA binding analyses indicate that NF-kappaB complexes change as colonocytes mature: p65-p50 complexes predominate in proliferating epithelial cells of the colon, whereas the p50-p50 dimer is prevalent in mature epithelial cells. NF-kappaB1 (p50) knockout mice were used to study the role of NF-kappaB in regulating epithelial cell turnover. Knockout animals lacked detectable NF-kappaB DNA binding activity in isolated epithelial cells and had significantly longer crypts with a more extensive proliferative zone than their wild-type counterparts (as determined by proliferating cell nuclear antigen staining and in vivo bromodeoxyuridine labeling). Gene expression profiling reveals that the NF-kappaB1 knockout mice express the potentially growth-enhancing tumor necrosis factor (TNF)-alpha and nerve growth factor-alpha genes at elevated levels, with in situ hybridization localizing some of the TNF-alpha expression to epithelial cells. TNF-alpha is NF-kappaB regulated, and its upregulation in NF-kappaB1 knockouts may result from an alleviation of p50-p50 repression. NF-kappaB complexes may therefore influence cell proliferation in the colon through their ability to selectively activate and/or repress gene expression.

  3. Estimating the electron energy distribution during ionospheric modification from spectrographic airglow measurements

    NASA Astrophysics Data System (ADS)

    Hysell, D. L.; Varney, R. H.; Vlasov, M. N.; Nossa, E.; Watkins, B.; Pedersen, T.; Huba, J. D.

    2012-02-01

    The electron energy distribution during an F region ionospheric modification experiment at the HAARP facility near Gakona, Alaska, is inferred from spectrographic airglow emission data. Emission lines at 630.0, 557.7, and 844.6 nm are considered along with the absence of detectable emissions at 427.8 nm. Estimating the electron energy distribution function from the airglow data is a problem in classical linear inverse theory. We describe an augmented version of the method of Backus and Gilbert which we use to invert the data. The method optimizes the model resolution, the precision of the mapping between the actual electron energy distribution and its estimate. Here, the method has also been augmented so as to limit the model prediction error. Model estimates of the suprathermal electron energy distribution versus energy and altitude are incorporated in the inverse problem formulation as representer functions. Our methodology indicates a heater-induced electron energy distribution with a broad peak near 5 eV that decreases approximately exponentially by 30 dB between 5-50 eV.

  4. The distribution of free electrons in the inner galaxy from pulsar dispersion measures

    NASA Technical Reports Server (NTRS)

    Harding, D. S.; Harding, A. K.

    1981-01-01

    The dispersion measures of a sample of 149 pulsars in the inner Galaxy (absolute value of l 50 deg) were statistically analyzed to deduce the large-scale distribution of free thermal electrons in this region. The dispersion measure distribution of these pulsars shows significant evidence for a decrease in the electron scale height from a local value greater than the pulsar scale height to a value less than the pulsar scale height at galactocentric radii inside of approximately 7 kpc. An increase in the electron density (to a value around .15/cu cm at 4 to 5 kpc) must accompany such a decrease in scale height. There is also evidence for a large-scale warp in the electron distribution below the b + 0 deg plane inside the Solar circle. A model is proposed for the electron distribution which incorporates these features and Monte Carlo generated dispersion measure distributions are presented for parameters which best reproduce the observed pulsar distributions.

  5. Immunoglobulin kappa light chain gene promoter and enhancer are not responsible for B-cell restricted gene rearrangement.

    PubMed Central

    Goodhardt, M; Babinet, C; Lutfalla, G; Kallenbach, S; Cavelier, P; Rougeon, F

    1989-01-01

    We have produced transgenic mice which synthesize chimeric mouse-rabbit immunoglobulin (Ig) kappa light chains following in vivo recombination of an injected unrearranged kappa gene. The exogenous gene construct contained a mouse germ-line kappa variable (V kappa) gene segment, the mouse germ-line joining (J kappa) locus including the enhancer, and the rabbit b9 constant (C kappa) region. A high level of V-J recombination of the kappa transgene was observed in spleen of the transgenic mice. Surprisingly, a particularly high degree of variability in the exact site of recombination and the presence of non germ-line encoded nucleotides (N-regions) were found at the V-J junction of the rearranged kappa transgene. Furthermore, unlike endogenous kappa genes, rearrangement of the exogenous gene occurred in T-cells of the transgenic mice. These results show that additional sequences, other than the heptamer-nonamer signal sequences and the promoter and enhancer elements, are required to obtain stage- and lineage- specific regulation of Ig kappa light chain gene rearrangement in vivo. Images PMID:2508061

  6. Characteristics of Electronegative Plasma Sheath with q-Nonextensive Electron Distribution

    NASA Astrophysics Data System (ADS)

    Borgohain, D. R.; Saharia, K.

    2018-01-01

    The characteristics of sheath in a plasma system containing q-nonextensive electrons, cold fluid ions, and Boltzmann-distributed negative ions are investigated. A modified Bohm sheath criterion is derived by using the Sagdeev pseudopotential technique. It is found that the proposed Bohm velocity depends on the degree of nonextensivity ( q), negative ion temperature to nonextensive electron temperature ratio (σ), and negative ion density ( B). Using the modified Bohm sheath criterion, the sheath characteristics, such as the spatial distribution of the potential, positive ion velocity, and density profile, have been numerically investigated, which clearly shows the effect of negative ions, as well as the nonextensive distribution of electrons. It is found that, as the nonextensivity parameter and the electronegativity increases, the electrostatic sheath potential increases sharply and the sheath width decreases.

  7. Electromagnetic Electron Cyclotron Instability in the Solar Wind

    NASA Astrophysics Data System (ADS)

    Lazar, M.; Yoon, P. H.; López, R. A.; Moya, P. S.

    2018-01-01

    The abundant reports on the existence of electromagnetic high-frequency fluctuations in space plasmas have increased the expectations that theoretical modeling may help understand their origins and implications (e.g., kinetic instabilities and dissipation). This paper presents an extended quasi-linear approach of the electromagnetic electron cyclotron instability in conditions typical for the solar wind, where the anisotropic electrons (T⊥>T∥) exhibit a dual distribution combining a bi-Maxwellian core and bi-Kappa halo. Involving both the core and halo populations, the instability is triggered by the cumulative effects of these components, mainly depending of their anisotropies. The instability is not very sensitive to the shape of halo distribution function conditioned in this case by the power index κ. This result seems to be a direct consequence of the low density of electron halo, which is assumed more dilute than the core component in conformity with the observations in the ecliptic. Quasi-linear time evolutions predicted by the theory are confirmed by the particle-in-cell simulations, which also suggest possible explanations for the inherent differences determined by theoretical constraints. These results provide premises for an advanced methodology to characterize, realistically, the electromagnetic electron cyclotron instability and its implication in the solar wind.

  8. Nuclear factor-kappaB activation correlates with better prognosis and Akt activation in human gastric cancer.

    PubMed

    Lee, Byung Lan; Lee, Hye Seung; Jung, Jieun; Cho, Sung Jin; Chung, Hee-Yong; Kim, Woo Ho; Jin, Young-Woo; Kim, Chong Soon; Nam, Seon Young

    2005-04-01

    Because the biological significance of constitutive nuclear factor-kappaB (NF-kappaB) activation in human gastric cancer is unclear, we undertook this study to clarify the regulatory mechanism of NF-kappaB activation and its clinical significance. Immunohistochemistry for NF-kappaB/RelA was done on 290 human gastric carcinoma specimens placed on tissue array slides. The correlations between NF-kappaB activation and clinicopathologic features, prognosis, Akt activation, tumor suppressor gene expression, or Bcl-2 expression were analyzed. We also did luciferase reporter assay, Western blot analysis, and reverse transcription-PCR using the SNU-216 human gastric cancer cell line transduced with retroviral vectors containing constitutively active Akt or the NF-kappaB repressor mutant of IkappaBalpha. Nuclear expression of RelA was found in 18% of the gastric carcinomas and was higher in early-stage pathologic tumor-node-metastasis (P = 0.019). A negative correlation was observed between NF-kappaB activation and lymphatic invasion (P = 0.034) and a positive correlation between NF-kappaB activation and overall survival rate of gastric cancer patients (P = 0.0228). In addition, NF-kappaB activation was positively correlated with pAkt (P = 0.047), p16 (P = 0.004), adenomatous polyposis coli (P < 0.001), Smad4 (P = 0.002), and kangai 1 (P < 0.001) expression. An in vitro study showed that NF-kappaB activity in gastric cancer cells is controlled by and controls Akt. NF-kappaB activation was frequently observed in early-stage gastric carcinoma and was significantly correlated with better prognosis and Akt activation. These findings suggest that NF-kappaB activation is a valuable prognostic variable in gastric carcinoma.

  9. Different effects of antisense RelA p65 and NF-kappaB1 p50 oligonucleotides on the nuclear factor-kappaB mediated expression of ICAM-1 in human coronary endothelial and smooth muscle cells.

    PubMed

    Voisard, R; Huber, N; Baur, R; Susa, M; Ickrath, O; Both, A; Koenig, W; Hombach, V

    2001-01-01

    Activation of nuclear factor-kappaB (NF-kappaB) is one of the key events in early atherosclerosis and restenosis. We hypothesized that tumor necrosis factor-alpha (TNF-alpha) induced and NF-kappaB mediated expression of intercellular adhesion molecule-1 (ICAM-1) can be inhibited by antisense RelA p65 and NF-kappaB1 p50 oligonucleotides (RelA p65 and NF-kappaB1 p50). Smooth muscle cells (SMC) from human coronary plaque material (HCPSMC, plaque material of 52 patients), SMC from the human coronary media (HCMSMC), human endothelial cells (EC) from umbilical veins (HUVEC), and human coronary EC (HCAEC) were successfully isolated (HCPSMC, HUVEC), identified and cultured (HCPSMC, HCMSMC, HUVEC, HCAEC). 12 hrs prior to TNF-alpha stimulus (20 ng/mL, 6 hrs) RelA p65 and NF-kappaB1 p50 (1, 2, 4, 10, 20, and 30 microM) and controls were added for a period of 18 hrs. In HUVEC and HCAEC there was a dose dependent inhibition of ICAM-1 expression after adding of both RelA p65 and NF-kappaB1 p50. No inhibitory effect was seen after incubation of HCMSMC with RelA p65 and NF-kappaB1 p50. A moderate inhibition of ICAM-1 expression was found after simultaneous addition of RelA p65 and NF-kappaB1 p50 to HCPSMC, no inhibitory effect was detected after individual addition of RelA p65 and NF-kappaB1 p50. The data point out that differences exist in the NF-kappaB mediated expression of ICAM-1 between EC and SMC. Experimental antisense strategies directed against RelA p65 and NF-kappaB1 p50 in early atherosclerosis and restenosis are promising in HCAEC but will be confronted with redundant pathways in HCMSMC and HCPSMC.

  10. Spectroscopic Measurements of the Ion Velocity Distribution at the Base of the Fast Solar Wind

    NASA Astrophysics Data System (ADS)

    Jeffrey, Natasha L. S.; Hahn, Michael; Savin, Daniel W.; Fletcher, Lyndsay

    2018-03-01

    In situ measurements of the fast solar wind reveal non-thermal distributions of electrons, protons, and minor ions extending from 0.3 au to the heliopause. The physical mechanisms responsible for these non-thermal properties and the location where these properties originate remain open questions. Here, we present spectroscopic evidence, from extreme ultraviolet spectroscopy, that the velocity distribution functions (VDFs) of minor ions are already non-Gaussian at the base of the fast solar wind in a coronal hole, at altitudes of <1.1 R ⊙. Analysis of Fe, Si, and Mg spectral lines reveals a peaked line-shape core and broad wings that can be characterized by a kappa VDF. A kappa distribution fit gives very small kappa indices off-limb of κ ≈ 1.9–2.5, indicating either (a) ion populations far from thermal equilibrium, (b) fluid motions such as non-Gaussian turbulent fluctuations or non-uniform wave motions, or (c) some combination of both. These observations provide important empirical constraints for the source region of the fast solar wind and for the theoretical models of the different acceleration, heating, and energy deposition processes therein. To the best of our knowledge, this is the first time that the ion VDF in the fast solar wind has been probed so close to its source region. The findings are also a timely precursor to the upcoming 2018 launch of the Parker Solar Probe, which will provide the closest in situ measurements of the solar wind at approximately 0.04 au (8.5 solar radii).

  11. The radiant ephemerides of kappa-Cygnids from the IMO video database

    NASA Astrophysics Data System (ADS)

    Triglav-Cekada, Mihaela

    2006-08-01

    The analysis of single-station IMO video network data of the July and August period with 36 576 meteors in search of kappa-Cygnid, alpha-Lyrid and zeta-Draconid meteor showers was made using the program Radiant. These showers will be named kappa-Cygnid meteor complex radiants. The detailed analysis of the whole August period from 1993-2004 included the behavior of radiants in different magnitude ranges and different years from 2000 on. Detailed radiant calculations for different velocities for 5g and 10g solar longitude intervals were also done. In 10g solar longitude intervals also the calculations for different magnitude ranges were conducted. The activity of the kappa-Cygnid radiant and the alpha-Lyrid radiant was proven, unlike the zeta-Draconid radiant, where no activity could be confirmed. For the whole August period also the behavior of radiants in separate years 2000-2004, when day-to-day meteor coverage is available, was made. From that it can be hinted on alternating bigger activity of the kappa-Cygnid and alpha-Lyrid radiants. In the years 2000 and 2001 the alpha-Lyrid radiant is more active, when on the contrary in 2002, 2003 and 2004 the kappa-Cygnid radiant is more active. The year 2003 is interesting from another aspect, as three radiants can be seen. If the third radiant is the zeta-Draconid radiant, a few years more video observations will have to be gathered and the radiant calculations repeated. For the day of the kappa-Cygnid meteor complex maximum, on August 18, the mean radiant positions were deduced: the more active kappa-Cygnid radiant lies at alpha=280 deg and delta=+58 deg with an area of the maximum probability of 10 deg x 15 deg, and the less active alpha-Lyrid radiant is placed at alpha=292 deg and delta=+52 deg with a radius of maximum probability of 2 deg. The radiant drift was not possible to obtain as in the 5 deg and 10 deg solar longitude interval calculations the positions of both radiants apparently oscillate. As no change can

  12. Electronically Distributed Work Communities: Implications for Research on Telework.

    ERIC Educational Resources Information Center

    Hesse, Bradford W.; Grantham, Charles E.

    1991-01-01

    Describes the concept of telework, or telecommuting, and its influence on the electronic community and organizational structures. The electronically distributed organization is discussed, and implications for research on telework are suggested in the areas of privacy regulation, self-efficacy, temporal aspects of employee behavior, communication…

  13. A new structural class of proteasome inhibitors that prevent NF-kappa B activation.

    PubMed

    Lum, R T; Kerwar, S S; Meyer, S M; Nelson, M G; Schow, S R; Shiffman, D; Wick, M M; Joly, A

    1998-05-01

    The multicatalytic proteinase or proteasome is a highly conserved cellular structure that is responsible for the ATP-dependent proteolysis of many proteins involved in important regulatory cellular processes. We have identified a novel class of inhibitors of the chymotrypsin-like proteolytic activity of the 20S proteasome that exhibit IC50 values ranging from 0.1 to 0.5 microgram/mL (0.1 to 1 microM). In cell proliferation assays, these compounds inhibit growth with an IC50 ranging from 5 to 10 micrograms/mL (10-20 microM). A representative member of this class of inhibitors was tested in other biological assays. CVT-634 (5-methoxy-1-indanone-3-acetyl-leu-D-leu-1-indanylamide) prevented lipopolysaccharide (LPS), tumor necrosis factor (TNF)-, and phorbol ester-induced activation of nuclear factor kappa B (NF-kappa B) in vitro by preventing signal-induced degradation of I kappa B-alpha. In these studies, the I kappa B-alpha that accumulated was hyperphosphorylated, indicating that CVT-634 did not inhibit I kappa B-alpha kinase, the enzyme responsible for signal-induced phosphorylation of I kappa B-alpha. In vivo studies indicated that CVT-634 prevented LPS-induced TNF synthesis in a murine macrophage cell line. In addition, in mice pretreated with CVT-634 at 25 and 50 mg/kg and subsequently treated with LPS, serum TNF levels were significantly lower (225 +/- 59 and 83 +/- 41 pg/mL, respectively) than in those mice that were treated only with LPS (865 +/- 282 pg/mL). These studies suggest that specific inhibition of the chymotrypsin-like activity of the proteasome is sufficient to prevent signal-induced NF-kappa B activation and that the proteasome is a novel target for the identification of agents that may be useful in the treatment of diseases whose etiology is dependent upon the activation of NF-kappa B.

  14. Respiratory syncytial virus M2-1 protein induces the activation of nuclear factor kappa B

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Reimers, Kerstin; Buchholz, Katja; Werchau, Hermann

    2005-01-20

    Respiratory syncytial virus (RSV) induces the production of a number of cytokines and chemokines by activation of nuclear factor kappa B (NF-{kappa}B). The activation of NF-{kappa}B has been shown to depend on viral replication in the infected cells. In this study, we demonstrate that expression of RSV M2-1 protein, a transcriptional processivity and anti-termination factor, is sufficient to activate NF-{kappa}B in A549 cells. Electromobility shift assays show increased NF-{kappa}B complexes in the nuclei of M2-1-expressing cells. M2-1 protein is found in nuclei of M2-1-expressing cells and in RSV-infected cells. Co-immunoprecipitations of nuclear extracts of M2-1-expressing cells and of RSV-infected cellsmore » revealed an association of M2-1 with Rel A protein. Furthermore, the activation of NF-{kappa}B depends on the C-terminus of the RSV M2-1 protein, as shown by NF-{kappa}B-induced gene expression of a reporter gene construct.« less

  15. BFV activates the NF-kappaB pathway through its transactivator (BTas) to enhance viral transcription

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang Jian; Tan Juan; Zhang Xihui

    2010-05-10

    Multiple families of viruses have evolved sophisticated strategies to regulate nuclear factor-kappaB (NF-kappaB) signaling, which plays a pivotal role in diverse cellular events, including virus-host interactions. In this study, we report that bovine foamy virus (BFV) is able to activate the NF-kappaB pathway through the action of its transactivator, BTas. Both cellular IKKbeta and IkappaBalpha also participate in this activation. In addition, we demonstrate that BTas induces the processing of p100, which implies that BTas can activate NF-kappaB through a noncanonical pathway as well. Co-immunoprecipitation analysis shows that BTas interacts with IKK catalytic subunits (IKKalpha and IKKbeta), which may bemore » responsible for regulation of IKK kinase activity and persistent NF-kappaB activation. Furthermore, our results indicate that the level of BTas-mediated LTR transcription correlates with the activity of cellular NF-kappaB. Together, this study suggests that BFV activates the NF-kappaB pathway through BTas to enhance viral transcription.« less

  16. BFV activates the NF-kappaB pathway through its transactivator (BTas) to enhance viral transcription.

    PubMed

    Wang, Jian; Tan, Juan; Zhang, Xihui; Guo, Hongyan; Zhang, Qicheng; Guo, Tingting; Geng, Yunqi; Qiao, Wentao

    2010-05-10

    Multiple families of viruses have evolved sophisticated strategies to regulate nuclear factor-kappaB (NF-kappaB) signaling, which plays a pivotal role in diverse cellular events, including virus-host interactions. In this study, we report that bovine foamy virus (BFV) is able to activate the NF-kappaB pathway through the action of its transactivator, BTas. Both cellular IKKbeta and IkappaBalpha also participate in this activation. In addition, we demonstrate that BTas induces the processing of p100, which implies that BTas can activate NF-kappaB through a noncanonical pathway as well. Co-immunoprecipitation analysis shows that BTas interacts with IKK catalytic subunits (IKKalpha and IKKbeta), which may be responsible for regulation of IKK kinase activity and persistent NF-kappaB activation. Furthermore, our results indicate that the level of BTas-mediated LTR transcription correlates with the activity of cellular NF-kappaB. Together, this study suggests that BFV activates the NF-kappaB pathway through BTas to enhance viral transcription. Copyright 2010 Elsevier Inc. All rights reserved.

  17. The kappa-opiate receptor impacts the pathophysiology and behavior of substance use.

    PubMed

    Mysels, David; Sullivan, Maria A

    2009-01-01

    There is increasing evidence that the kappa-opiate receptor, in addition to the mu-opiate receptor, plays an important role in substance use pathophysiology and behavior. As dopamine activity is upregulated through chronic substance use, kappa receptor activity, mediated through the peptide dynorphin, is upregulated in parallel. Dynorphin causes dysphoria and decreased locomotion, and the upregulation of its activity on the kappa receptor likely dampens the excitation caused by increased dopaminergic activity. This feedback mechanism may have significant clinical implications for treating drug dependent patients in various stages of their pathology.

  18. Polycystin-1 promotes PKC{alpha}-mediated NF-{kappa}B activation in kidney cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Banzi, Manuela; Aguiari, Gianluca; Trimi, Viky

    2006-11-17

    Polycystin-1 (PC1), the PKD1 gene product, is a membrane receptor which regulates many cell functions, including cell proliferation and apoptosis, both typically increased in cyst lining cells in autosomal dominant polycystic kidney disease. Here we show that PC1 upregulates the NF-{kappa}B signalling pathway in kidney cells to prevent cell death. Human embryonic kidney cell lines (HEK293{sup CTT}), stably expressing a PC1 cytoplasmic terminal tail (CTT), presented increased NF-{kappa}B nuclear levels and NF-{kappa}B-mediated luciferase promoter activity. This, consistently, was reduced in HEK293 cells in which the endogenous PC1 was depleted by RNA interference. CTT-dependent NF-{kappa}B promoter activation was mediated by PKC{alpha}more » because it was blocked by its specific inhibitor Ro-320432. Furthermore, it was observed that apoptosis, which was increased in PC1-depleted cells, was reduced in HEK293{sup CTT} cells and in porcine kidney LtTA cells expressing a doxycycline-regulated CTT. Staurosporine, a PKC inhibitor, and parthenolide, a NF-{kappa}B inhibitor, significantly reduced the CTT-dependent antiapoptotic effect. These data reveal, therefore, a novel pathway by which polycystin-1 activates a PKC{alpha}-mediated NF-{kappa}B signalling and cell survival.« less

  19. Resonant interatomic Coulombic decay in HeNe: Electron angular emission distributions

    NASA Astrophysics Data System (ADS)

    Mhamdi, A.; Trinter, F.; Rauch, C.; Weller, M.; Rist, J.; Waitz, M.; Siebert, J.; Metz, D.; Janke, C.; Kastirke, G.; Wiegandt, F.; Bauer, T.; Tia, M.; Cunha de Miranda, B.; Pitzer, M.; Sann, H.; Schiwietz, G.; Schöffler, M.; Simon, M.; Gokhberg, K.; Dörner, R.; Jahnke, T.; Demekhin, Ph. Â. V.

    2018-05-01

    We present a joint experimental and theoretical study of resonant interatomic Coulombic decay (RICD) in HeNe employing high resolution cold target recoil ion momentum spectroscopy and ab initio electronic structure and nuclear dynamics calculations. In particular, laboratory- and molecular-frame angular emission distributions of RICD electrons are examined in detail. The exciting-photon energy-dependent anisotropy parameter β (ω ) , measured for decay events that populate bound HeNe+ ions, is in agreement with the calculations performed for the ground ionic state X2Σ1/2 + . A contribution from the a2Π3 /2 final ionic state is found to be negligible. For the He +Ne+ fragmentation channel, the observed laboratory-frame angular distribution of RICD electrons is explained by a slow homogeneous dissociation of bound vibrational levels of the final ionic state A2Π1 /2 into vibrational continua of the lower lying states X2Σ1/2 + and a2Π3 /2 . Our calculations predict that the angular distributions of RICD electrons in the body-fixed dipole plane provide direct access to the electronic character (i.e., symmetry) of intermediate vibronic resonances. However, because of the very slow dissociation of the A2Π1 /2 state, the molecular-frame angular distributions of RICD electrons in the He +Ne+ fragmentation channel are inaccessible to our coincidence experiment.

  20. NF-{kappa}B inhibition is involved in tobacco smoke-induced apoptosis in the lungs of rats

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhong Caiyun; Zhou Yamei; Pinkerton, Kent E.

    2008-07-15

    Apoptosis is a vital mechanism for the regulation of cell turnover and plays a critical role in tissue homeostasis and development of many disease processes. Previous studies have demonstrated the apoptotic effect of tobacco smoke; however, the molecular mechanisms by which tobacco smoke triggers apoptosis remain unclear. In the present study we investigated the effects of tobacco smoke on the induction of apoptosis in the lungs of rats and modulation of nuclear factor-kappa B (NF-{kappa}B) in this process. Exposure of rats to 80 mg/m{sup 3} tobacco smoke significantly induced apoptosis in the lungs. Tobacco smoke resulted in inhibition of NF-{kappa}Bmore » activity, noted by suppression of inhibitor of {kappa}B (I{kappa}B) kinase (IKK), accumulation of I{kappa}B{alpha}, decrease of NF-{kappa}B DNA binding activity, and downregulation of NF-{kappa}B-dependent anti-apoptotic proteins, including Bcl-2, Bcl-xl, and inhibitors of apoptosis. Initiator caspases for the death receptor pathway (caspase 8) and the mitochondrial pathway (caspase 9) as well as effector caspase 3 were activated following tobacco smoke exposure. Tobacco smoke exposure did not alter the levels of p53 and Bax proteins. These findings suggest the role of NF-{kappa}B pathway in tobacco smoke-induced apoptosis.« less

  1. Corrective recombination of mouse immunoglobulin kappa alleles in Abelson murine leukemia virus-transformed pre-B cells.

    PubMed Central

    Feddersen, R M; Van Ness, B G

    1990-01-01

    Previous characterization of mouse immunoglobulin kappa gene rearrangement products cloned from murine plasmacytomas has indicated that two recombination events can take place on a single kappa allele (R. M. Feddersen and B. G. Van Ness, Proc. Natl. Acad. Sci. USA 82:4792-4797, 1985; M. A. Shapiro and M. Weigert, J. Immunol. 139:3834-3839, 1987). To determine whether multiple recombinations on a single kappa allele can contribute to the formation of productive V-J genes through corrective recombinations, we have examined several Abelson murine leukemia virus-transformed pre-B-cell clones which rearrange the kappa locus during cell culture. Clonal cell lines which had rearranged one kappa allele nonproductively while maintaining the other allele in the germ line configuration were grown, and secondary subclones, which subsequently expressed kappa protein, were isolated and examined for further kappa rearrangement. A full spectrum of rearrangement patterns was observed in this sequential cloning, including productive and nonproductive recombinations of the germ line allele and secondary recombinations of the nonproductive allele. The results show that corrective V-J recombinations, with displacement of the nonproductive kappa gene, occur with a significant frequency (6 of 17 kappa-producing subclones). Both deletion and maintenance of the primary (nonfunctional) V-J join, as a reciprocal product, were observed. Images PMID:2153918

  2. Spatiotemporal Evolution of Runaway Electron Momentum Distributions in Tokamaks

    DOE PAGES

    Paz-Soldan, Carlos; Cooper, Christopher M.; Aleynikov, Pavel; ...

    2017-06-22

    Novel spatial, temporal, and energetically resolved measurements of bremsstrahlung hard-x-ray (HXR) emission from runaway electron (RE) populations in tokamaks reveal nonmonotonic RE distribution functions whose properties depend on the interplay of electric field acceleration with collisional and synchrotron damping. Measurements are consistent with theoretical predictions of momentum-space attractors that accumulate runaway electrons. RE distribution functions are measured to shift to a higher energy when the synchrotron force is reduced by decreasing the toroidal magnetic field strength. Increasing the collisional damping by increasing the electron density (at a fixed magnetic and electric field) reduces the energy of the nonmonotonic feature andmore » reduces the HXR growth rate at all energies. Higher-energy HXR growth rates extrapolate to zero at the expected threshold electric field for RE sustainment, while low-energy REs are anomalously lost. The compilation ofHXR emission from different sight lines into the plasma yields energy and pitch-angle-resolved RE distributions and demonstrates increasing pitch-angle and radial gradients with energy.« less

  3. Identification of a novel A20-binding inhibitor of nuclear factor-kappa B activation termed ABIN-2.

    PubMed

    Van Huffel, S; Delaei, F; Heyninck, K; De Valck, D; Beyaert, R

    2001-08-10

    The nuclear factor kappaB (NF-kappaB) plays a central role in the regulation of genes implicated in immune responses, inflammatory processes, and apoptotic cell death. The zinc finger protein A20 is a cellular inhibitor of NF-kappaB activation by various stimuli and plays a critical role in terminating NF-kappaB responses. The underlying mechanism for NF-kappaB inhibition by A20 is still unknown. A20 has been shown to interact with several proteins including tumor necrosis factor (TNF) receptor-associated factors 2 and 6, as well as the inhibitory protein of kappaB kinase (IKK) gamma protein. Here we report the cloning and characterization of ABIN-2, a previously unknown protein that binds to the COOH-terminal zinc finger domain of A20. NF-kappaB activation induced by TNF and interleukin-1 is inhibited by overexpression of ABIN-2. The latter also inhibits NF-kappaB activation induced by overexpression of receptor-interacting protein or TNF receptor-associated factor 2. In contrast, NF-kappaB activation by overexpression of IKKbeta or direct activators of the IKK complex, such as Tax, cannot be inhibited by ABIN-2. These results indicate that ABIN-2 interferes with NF-kappaB activation upstream of the IKK complex and that it might contribute to the NF-kappaB-inhibitory function of A20.

  4. A Concept for Measuring Electron Distribution Functions Using Collective Thomson Scattering

    NASA Astrophysics Data System (ADS)

    Milder, A. L.; Froula, D. H.

    2017-10-01

    A.B. Langdon proposed that stable non-Maxwellian distribution functions are realized in coronal inertial confinement fusion plasmas via inverse bremsstrahlung heating. For Zvosc2 Zvosc2 vth2 > 1 , vth2 > 1 , the inverse bremsstrahlung heating rate is sufficiently fast to compete with electron-electron collisions. This process preferentially heats the subthermal electrons leading to super-Gaussian distribution functions. A method to identify the super-Gaussian order of the distribution functions in these plasmas using collective Thomson scattering will be proposed. By measuring the collective Thomson spectra over a range of angles the density, temperature and super-Gaussian order can be determined. This is accomplished by fitting non-Maxwellian distribution data with a super-Gaussian model; in order to match the density and electron temperature to within 10%, the super-Gaussian order must be varied. This material is based upon work supported by the Department of Energy National Nuclear Security Administration under Award Number DE-NA0001944.

  5. Regulation of the nuclear factor (NF)-kappaB pathway by ISGylation.

    PubMed

    Minakawa, Miki; Sone, Takayuki; Takeuchi, Tomoharu; Yokosawa, Hideyoshi

    2008-12-01

    Post-translational modification with ISG15 (interferon-stimulated gene 15 kDa) (ISGylation) is mediated by a sequential reaction similar to ubiquitination, and various target proteins for ISGylation have been identified. We previously reported that ISGylation of the E2 ubiquitin-conjugating enzyme Ubc13 suppresses its E2 activity. Ubc13 forms a heterodimer with Uev1A, a ubiquitin-conjugating enzyme variant, and the Ubc13-Uev1A complex catalyzes the assembly of a Lys63-linked polyubiquitin chain, which plays a non-proteolytic role in the nuclear factor (NF)-kappaB pathway. In this study, we examined the effect of ISGylation on tumor necrosis factor receptor-associated factor (TRAF)-6/transforming growth factor beta-activated kinase (TAK)-1-dependent NF-kappaB activation. We found that expression of the ISGylation system suppresses NF-kappaB activation via TRAF6 and TAK1 and that the level of polyubiquitinated TRAF6 is reduced by expression of the ISGylation system. Taken together, the results suggest that the NF-kappaB pathway is negatively regulated by ISGylation.

  6. Role of kappa-casein in the association of denatured whey proteins with casein micelles in heated reconstituted skim milk.

    PubMed

    Anema, Skelte G

    2007-05-02

    Reconstituted skim milk at pH from 6.5 to 7.1 was unheated, preheated (68 degrees C/20 min), or heated at 90 degrees C for 20-30 min. On preheating, the size of the casein micelles decreased by about 5-20 nm, with a greater effect at higher pH. The casein micelle size of the heated milk at pH 6.5 increased by about 30 nm when compared to that of the unheated or preheated milk. As the pH was increased before heating, the particle size gradually decreased so that, at pH 7.1, the size was markedly smaller than that for the unheated milk and slightly smaller than that for the preheated milk. High levels (about 85%) of denatured whey protein associated with the casein micelles at pH 6.5, and this level decreased as the pH increased so that, at pH 7.1, low levels (about 15%) were associated with the micelles. Low levels of alphaS-casein and beta-casein were found in the serum regardless of the heat treatment or the pH of the milk. At pH 6.5, low levels (about 10%) of kappa-casein were also found in the milk serum. In the unheated milk, the level of serum kappa-casein increased slightly with increasing pH; in the heated samples, the level of serum kappa-casein increased markedly and linearly with increasing pH so that, at pH 7.1, about 70% of the kappa-casein was in the serum phase. The results of this study indicate that the pH dependence of the levels of serum phase kappa-casein may be responsible for the change in distribution of the whey proteins between the colloidal and serum phases. This is the first report to demonstrate significant levels of dissociation of kappa-casein from the micelles at pH between 6.5 and 6.7, although this dissociation phenomenon is well known on heating milk at high temperatures at pH above 6.7.

  7. Electron energy distribution function, effective electron temperature, and dust charge in the temporal afterglow of a plasma

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Denysenko, I. B.; Azarenkov, N. A.; Kersten, H.

    2016-05-15

    Analytical expressions describing the variation of electron energy distribution function (EEDF) in an afterglow of a plasma are obtained. Especially, the case when the electron energy loss is mainly due to momentum-transfer electron-neutral collisions is considered. The study is carried out for different EEDFs in the steady state, including Maxwellian and Druyvesteyn distributions. The analytical results are not only obtained for the case when the rate for momentum-transfer electron-neutral collisions is independent on electron energy but also for the case when the collisions are a power function of electron energy. Using analytical expressions for the EEDF, the effective electron temperaturemore » and charge of the dust particles, which are assumed to be present in plasma, are calculated for different afterglow durations. An analytical expression for the rate describing collection of electrons by dust particles for the case when the rate for momentum-transfer electron-neutral collisions is independent on electron energy is also derived. The EEDF profile and, as a result, the effective electron temperature and dust charge are sufficiently different in the cases when the rate for momentum-transfer electron-neutral collisions is independent on electron energy and when the rate is a power function of electron energy.« less

  8. RRM2 induces NF-{kappa}B-dependent MMP-9 activation and enhances cellular invasiveness

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Duxbury, Mark S.; Whang, Edward E.

    2007-03-02

    Ribonucleotide reductase is a dimeric enzyme that catalyzes conversion of ribonucleotide 5'-diphosphates to their 2'-deoxynucleotide forms, a rate-limiting step in the production of 2'-deoxyribonucleoside 5'-triphosphates required for DNA synthesis. The ribonucleotide reductase M2 subunit (RRM2) is a determinant of malignant cellular behavior in a range of human cancers. We examined the effect of RRM2 overexpression on pancreatic adenocarcinoma cellular invasiveness and nuclear factor-{kappa}B (NF-{kappa}B) transcription factor activity. RRM2 overexpression increases pancreatic adenocarcinoma cellular invasiveness and MMP-9 expression in a NF-{kappa}B-dependent manner. RNA interference (RNAi)-mediated silencing of RRM2 expression attenuates cellular invasiveness and NF-{kappa}B activity. NF-{kappa}B is a key mediator ofmore » the invasive phenotypic changes induced by RRM2 overexpression.« less

  9. African swine fever virus IAP-like protein induces the activation of nuclear factor kappa B.

    PubMed

    Rodríguez, Clara I; Nogal, María L; Carrascosa, Angel L; Salas, María L; Fresno, Manuel; Revilla, Yolanda

    2002-04-01

    African swine fever virus (ASFV) encodes a homologue of the inhibitor of apoptosis (IAP) that promotes cell survival by controlling the activity of caspase-3. Here we show that ASFV IAP is also able to activate the transcription factor NF-kappaB. Thus, transient transfection of the viral IAP increases the activity of an NF-kappaB reporter gene in a dose-responsive manner in Jurkat cells. Similarly, stably transfected cells expressing ASFV IAP have elevated basal levels of c-rel, an NF-kappaB-dependent gene. NF-kappaB complexes in the nucleus were increased in A224L-expressing cells compared with control cells upon stimulation with phorbol myristate acetate (PMA) plus ionomycin. This resulted in greater NF-kappaB-dependent promoter activity in ASFV IAP-expressing than in control cells, both in basal conditions and after PMA plus ionophore stimulation. The elevated NF-kappaB activity seems to be the consequence of higher IkappaB kinase (IKK) basal activity in these cells. The NF-kappaB-inducing activity of ASFV IAP was abrogated by an IKK-2 dominant negative mutant and enhanced by expression of tumor necrosis factor receptor-associated factor 2.

  10. NF-kappaB activation in hypothalamic pro-opiomelanocortin neurons is essential in illness- and leptin-induced anorexia.

    PubMed

    Jang, Pil-Geum; Namkoong, Cherl; Kang, Gil Myoung; Hur, Man-Wook; Kim, Seung-Whan; Kim, Geun Hyang; Kang, Yeoungsup; Jeon, Min-Jae; Kim, Eun Hee; Lee, Myung-Shik; Karin, Michael; Baik, Ja-Hyun; Park, Joong-Yeol; Lee, Ki-Up; Kim, Young-Bum; Kim, Min-Seon

    2010-03-26

    Anorexia and weight loss are prevalent in infectious diseases. To investigate the molecular mechanisms underlying these phenomena, we established animal models of infection-associated anorexia by administrating bacterial and viral products, lipopolysaccharide (LPS) and human immunodeficiency virus-1 transactivator protein (Tat). In these models, we found that the nuclear factor-kappaB (NF-kappaB), a pivotal transcription factor for inflammation-related proteins, was activated in the hypothalamus. In parallel, administration of LPS and Tat increased hypothalamic pro-inflammatory cytokine production, which was abrogated by inhibition of hypothalamic NF-kappaB. In vitro, NF-kappaB activation directly stimulated the transcriptional activity of pro-opiomelanocortin (POMC), a precursor of anorexigenic melanocortin, and mediated the stimulatory effects of LPS, Tat, and pro-inflammatory cytokines on POMC transcription, implying the involvement of NF-kappaB in controlling feeding behavior. Consistently, hypothalamic injection of LPS and Tat caused a significant reduction in food intake and body weight, which was prevented by blockade of NF-kappaB and melanocortin. Furthermore, disruption of I kappaB kinase-beta, an upstream kinase of NF-kappaB, in POMC neurons attenuated LPS- and Tat-induced anorexia. These findings suggest that infection-associated anorexia and weight loss are mediated via NF-kappaB activation in hypothalamic POMC neurons. In addition, hypothalamic NF-kappaB was activated by leptin, an important anorexigenic hormone, and mediates leptin-stimulated POMC transcription, indicating that hypothalamic NF-kappaB also serves as a downstream signaling pathway of leptin.

  11. Measurement of non-Maxwellian electron velocity distributions in a reflex discharge

    NASA Technical Reports Server (NTRS)

    Phipps, C. R., Jr.; Bershader, D.

    1978-01-01

    The results of a ruby laser Thomson scattering study of the space and time-resolved electron velocity distributions in a pulsed Penning discharge in hydrogen are presented. Electron densities were to the order of 10 to the 13th/cu cm and temperatures were roughly 3 eV. This point is just prior to the cessation of the discharge ohmic heating pulse. For magnetic strengths less than 200 G, Maxwellian distributions were found over an energy range six times thermal energy. Temperatures agreed with Langmuir probe data. For fields of 450 G, chaotic plasma potentials were observed to be unstable and the Thomson scattering showed that the electron velocity distributions had central temperatures of 2 eV and wing temperatures of 15-12 eV.

  12. Effect of anisotropic dust pressure and superthermal electrons on propagation and stability of dust acoustic solitary waves

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bashir, M. F., E-mail: frazbashir@yahoo.com; Behery, E. E., E-mail: eebehery@gmail.com; Department of Physics, Faculty of Science, Damietta University, P.O. 34517, New Damietta

    2015-06-15

    Employing the reductive perturbation technique, Zakharov–Kuznetzov (ZK) equation is derived for dust acoustic (DA) solitary waves in a magnetized plasma which consists the effects of dust anisotropic pressure, arbitrary charged dust particles, Boltzmann distributed ions, and Kappa distributed superthermal electrons. The ZK solitary wave solution is obtained. Using the small-k expansion method, the stability analysis for DA solitary waves is also discussed. The effects of the dust pressure anisotropy and the electron superthermality on the basic characteristics of DA waves as well as on the three-dimensional instability criterion are highlighted. It is found that the DA solitary wave is rarefactivemore » (compressive) for negative (positive) dust. In addition, the growth rate of instability increases rapidly as the superthermal spectral index of electrons increases with either positive or negative dust grains. A brief discussion for possible applications is included.« less

  13. Energy dependence of the spatial distribution of inelastically scattered electrons in backscatter electron diffraction

    NASA Astrophysics Data System (ADS)

    Ram, Farangis; De Graef, Marc

    2018-04-01

    In an electron backscatter diffraction pattern (EBSP), the angular distribution of backscattered electrons (BSEs) depends on their energy. Monte Carlo modeling of their depth and energy distributions suggests that the highest energy BSEs are more likely to hit the bottom of the detector than the top. In this paper, we examine experimental EBSPs to validate the modeled angular BSE distribution. To that end, the Kikuchi bandlet method is employed to measure the width of Kikuchi bands in both modeled and measured EBSPs. The results show that in an EBSP obtained with a 15 keV primary probe, the width of a Kikuchi band varies by about 0 .4∘ from the bottom of the EBSD detector to its top. The same is true for a simulated pattern that is composed of BSEs with 5 keV to 15 keV energies, which validates the Monte Carlo simulations.

  14. Phi Delta Kappa at the Threshold

    ERIC Educational Resources Information Center

    Walling, Donovan R.

    2006-01-01

    Since its fraternal origins a century ago, Phi Delta Kappa (PDK) International has been foremost a society of individuals joined together in professional collegiality and dedicated to tenets of leadership, service, and research in education. As PDK crosses the threshold into its second century, that early spirit of association lit in 1906, like…

  15. Persistent tumor necrosis factor signaling in normal human fibroblasts prevents the complete resynthesis of I kappa B-alpha.

    PubMed

    Poppers, D M; Schwenger, P; Vilcek, J

    2000-09-22

    Transcription factor NF-kappa B is normally sequestered in the cytoplasm, complexed with I kappa B inhibitory proteins. Tumor necrosis factor (TNF) and interleukin-1 induce I kappa B-alpha phosphorylation, leading to I kappa B-alpha degradation and translocation of NF-kappa B to the nucleus where it activates genes important in inflammatory and immune responses. TNF and interleukin-1 actions are typically terminated by desensitization, and I kappa B-alpha reappearance normally occurs within 30-60 min. We found that in normal human FS-4 fibroblasts maintained in the presence of TNF, I kappa B-alpha protein failed to return to base-line levels for up to 15 h. Removal of TNF at any time during the 15-h period resulted in complete I kappa B-alpha resynthesis, suggesting that I kappa B-alpha reappearance was prevented by continued TNF signaling. Long term exposure of FS-4 fibroblasts to TNF led to a persistent presence of I kappa B-alpha mRNA, sustained I kappa B kinase activation, continuous proteasome-mediated degradation of I kappa B-alpha, and sustained nuclear localization of NF-kappa B. Continuous exposure of FS-4 cells to TNF did not lead to a sustained activation of p38 or ERK mitogen-activated protein kinases, suggesting that not all TNF-induced signaling pathways are persistently activated. These findings challenge the notion that all cytokine-mediated signals are rapidly terminated by desensitization and illustrate the need to elucidate the process of deactivation of TNF-induced signaling.

  16. Electron Density Distribution Changes of Magnesiowüstite With Pressure

    NASA Astrophysics Data System (ADS)

    Diamond, M. R.; Popov, D.; Shen, G.; Jeanloz, R.

    2017-12-01

    Magnesiowüstite is one of the dominant minerals in the earth's lower mantle; its density and elasticity, substantially altered by its spin crossover, have direct consequence to interpreting deep-earth geophysical data. High-resolution single-crystal x-ray diffraction data can portray the 3-dimensional distribution of electron density through the Fourier transform of measured form factors. Here we present experimentally measured changes in electron density distribution of single-crystal (Mg.85,Fe.15)O as it goes through its iron(II) high-spin to low-spin electronic transition between about 40 and 60 GPa [Lin and Tsuchiya, 2008], in a diamond-anvil cell. As (Mg,Fe)O undergoes a pressure induced spin crossover (from high spin at low pressure to low spin at high pressure) due to overlap of its eg orbitals, the t2g orbitals become more pronounced to due a higher population of electrons, while the eg orbitals diminish. The spin splitting energy becomes increasingly unfavorable compared to the spin orbital pairing energy. By looking at the population of electrons at different directions in real space, we directly observe these changes in orbital occupation leading up to and during the spin crossover. Since high-Mg magnesiowüstite has a high symmetry structure at these pressure conditions, detecting relative changes in electron density distribution (comparing subsequent pressure steps) is feasible by collecting high resolution data offered by high-energy X rays and wide opening-angle diamond-anvil cells.

  17. ICI 204448: a kappa-opioid agonist with limited access to the CNS.

    PubMed Central

    Shaw, J. S.; Carroll, J. A.; Alcock, P.; Main, B. G.

    1989-01-01

    1. A number of compounds were evaluated in an attempt to identify a kappa-opioid receptor agonist with limited access to the central nervous system. 2. Quaternary derivatives of the kappa-opioid agonists tifluadom, U-50488H and ethylketocyclazocine were essentially devoid of opioid activity in a range of isolated tissue preparations. 3. A novel compound - ICI 204448 - is described which produced a potent and naloxone-reversible inhibition of electrically-evoked contraction of the guinea-pig ileum, mouse vas deferens and rabbit vas deferens preparations. ICI 204448 was shown to displace the binding of the kappa-opioid ligand [3H]-bremazocine from guinea-pig cerebellum membranes. 4. Ex vivo binding studies in mice showed ICI 204448 to be well absorbed following subcutaneous administration. The brain levels achieved by ICI 20448 were substantially lower than those produced by kappa-agonists such as U-50488H and tifluadom. 5. A good correlation was found for a range of opioids between lipophilicity and degree of CNS penetration. PMID:2568146

  18. Enhancement of wave growth for warm plasmas with a high-energy tail distribution

    NASA Technical Reports Server (NTRS)

    Thorne, Richard M.; Summers, Danny

    1991-01-01

    The classical linear theory of electromagnetic wave growth in a warm plasma is considered for waves propagating parallel to a uniform ambient magnetic field. Wave-growth rates are calculated for ion-driven right-hand mode waves for Kappa and Maxwellian particle distribution functions and for various values of the spectral index, the temperature anisotropy, and the ratio of plasma pressure to magnetic pressure appropriate to the solar wind. When the anisotropy is low the wave growth is limited to frequencies below the proton gyrofrequency and the growth rate increases dramatically as the spectral index is reduced. The growth rate for any Kappa distribution greatly exceeds that for a Maxwellian with the same bulk properties. For large thermal anisotropy the growth rate from either distribution is greatly enhanced. The growth rates from a Kappa distribution are generally larger than for a Maxwellian distribution, and significant wave growth occurs over a broader range of frequencies.

  19. Characterisation of mega-voltage electron pencil beam dose distributions: viability of a measurement-based approach.

    PubMed

    Barnes, M P; Ebert, M A

    2008-03-01

    The concept of electron pencil-beam dose distributions is central to pencil-beam algorithms used in electron beam radiotherapy treatment planning. The Hogstrom algorithm, which is a common algorithm for electron treatment planning, models large electron field dose distributions by the superposition of a series of pencil beam dose distributions. This means that the accurate characterisation of an electron pencil beam is essential for the accuracy of the dose algorithm. The aim of this study was to evaluate a measurement based approach for obtaining electron pencil-beam dose distributions. The primary incentive for the study was the accurate calculation of dose distributions for narrow fields as traditional electron algorithms are generally inaccurate for such geometries. Kodak X-Omat radiographic film was used in a solid water phantom to measure the dose distribution of circular 12 MeV beams from a Varian 21EX linear accelerator. Measurements were made for beams of diameter, 1.5, 2, 4, 8, 16 and 32 mm. A blocked-field technique was used to subtract photon contamination in the beam. The "error function" derived from Fermi-Eyges Multiple Coulomb Scattering (MCS) theory for corresponding square fields was used to fit resulting dose distributions so that extrapolation down to a pencil beam distribution could be made. The Monte Carlo codes, BEAM and EGSnrc were used to simulate the experimental arrangement. The 8 mm beam dose distribution was also measured with TLD-100 microcubes. Agreement between film, TLD and Monte Carlo simulation results were found to be consistent with the spatial resolution used. The study has shown that it is possible to extrapolate narrow electron beam dose distributions down to a pencil beam dose distribution using the error function. However, due to experimental uncertainties and measurement difficulties, Monte Carlo is recommended as the method of choice for characterising electron pencil-beam dose distributions.

  20. Linear and Nonlinear Coupling of Electrostatic Drift and Acoustic Perturbations in a Nonuniform Bi-Ion Plasma with Non-Maxwellian Electrons

    NASA Astrophysics Data System (ADS)

    Ali, Gul-e.; Ahmad, Ali; Masood, W.; Mirza, Arshad M.

    2017-12-01

    Linear and nonlinear coupling of drift and ion acoustic waves are studied in a nonuniform magnetized plasma comprising of Oxygen and Hydrogen ions with nonthermal distribution of electrons. It has been observed that different ratios of ion number densities and kappa and Cairns distributed electrons significantly modify the linear dispersion characteristics of coupled drift-ion acoustic waves. In the nonlinear regime, KdV (for pure drift waves) and KP (for coupled drift-ion acoustic waves) like equations have been derived to study the nonlinear evolution of drift solitary waves in one and two dimensions. The dependence of drift solitary structures on different ratios of ion number densities and nonthermal distribution of electrons has also been explored in detail. It has been found that the ratio of the diamagnetic drift velocity to the velocity of the nonlinear structure determines the existence regimes for the drift solitary waves. The present investigation may be beneficial to understand the formation of solitons in the ionospheric F-region.

  1. Electron Source Brightness and Illumination Semi-Angle Distribution Measurement in a Transmission Electron Microscope.

    PubMed

    Börrnert, Felix; Renner, Julian; Kaiser, Ute

    2018-05-21

    The electron source brightness is an important parameter in an electron microscope. Reliable and easy brightness measurement routes are not easily found. A determination method for the illumination semi-angle distribution in transmission electron microscopy is even less well documented. Herein, we report a simple measurement route for both entities and demonstrate it on a state-of-the-art instrument. The reduced axial brightness of the FEI X-FEG with a monochromator was determined to be larger than 108 A/(m2 sr V).

  2. The LIM-homeodomain transcription factor LMX1B regulates expression of NF-kappa B target genes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rascle, Anne; Neumann, Tanja; Raschta, Anne-Sarah

    2009-01-01

    LMX1B is a LIM-homeodomain transcription factor essential for development. Putative LMX1B target genes have been identified through mouse gene targeting studies, but their identity as direct LMX1B targets remains hypothetical. We describe here the first molecular characterization of LMX1B target gene regulation. Microarray analysis using a tetracycline-inducible LMX1B expression system in HeLa cells revealed that a subset of NF-{kappa}B target genes, including IL-6 and IL-8, are upregulated in LMX1B-expressing cells. Inhibition of NF-{kappa}B activity by short interfering RNA-mediated knock-down of p65 impairs, while activation of NF-{kappa}B activity by TNF-{alpha} synergizes induction of NF-{kappa}B target genes by LMX1B. Chromatin immunoprecipitation demonstratedmore » that LMX1B binds to the proximal promoter of IL-6 and IL-8 in vivo, in the vicinity of the characterized {kappa}B site, and that LMX1B recruitment correlates with increased NF-{kappa}B DNA association. IL-6 promoter-reporter assays showed that the {kappa}B site and an adjacent putative LMX1B binding motif are both involved in LMX1B-mediated transcription. Expression of NF-{kappa}B target genes is affected in the kidney of Lmx1b{sup -/-} knock-out mice, thus supporting the biological relevance of our findings. Together, these data demonstrate for the first time that LMX1B directly regulates transcription of a subset of NF-{kappa}B target genes in cooperation with nuclear p50/p65 NF-{kappa}B.« less

  3. A new gene in A. rubens: A sea star Ig kappa gene.

    PubMed

    Vincent, Nadine; Osteras, Magne; Otten, Patricia; Leclerc, Michel

    2014-12-01

    The sea star Asterias rubens reacts specifically to the antigen:HRP (horse-radish peroxydase) and produces an antibody anti-HRP. We previously identified a candidate Ig kappa gene corresponding to this manuscript. We show now the gene referred to as: "sea star Ig kappa gene in its specificity".

  4. NF-kappaB mediates mitogen-activated protein kinase pathway-dependent iNOS expression in human melanoma.

    PubMed

    Uffort, Deon G; Grimm, Elizabeth A; Ellerhorst, Julie A

    2009-01-01

    Tumor expression of inducible nitric oxide synthase (iNOS) predicts poor outcomes for melanoma patients. We have reported the regulation of melanoma iNOS by the mitogen-activated protein kinase (MAPK) pathway. In this study, we test the hypothesis that NF-kappaB mediates this regulation. Western blotting of melanoma cell lysates confirmed the constitutive expression of iNOS. Western blot detected baseline levels of activated nuclear extracellular signal-regulated kinase and NF-kappaB. Indirect immunofluorescence confirmed the presence of NF-kappaB p50 and p65 in melanoma cell nuclei, with p50 being more prevalent. Electrophoretic mobility shift assay demonstrated baseline NF-kappaB activity, the findings confirmed by supershift analysis. Treatment of melanoma cells with the MEK inhibitor U0126 decreased NF-kappaB binding to its DNA recognition sequence, implicating the MAPK pathway in NF-kappaB activation. Two specific NF-kappaB inhibitors suppressed iNOS expression, demonstrating regulation of iNOS by NF-kappaB. Several experiments indicated the presence of p50 homodimers, which lack a transactivation domain and rely on the transcriptional coactivator Bcl-3 to carry out this function. Bcl-3 was detected in melanoma cells and co-immunoprecipitated with p50. These data suggest that the constitutively activated melanoma MAPK pathway stimulates activation of NF-kappaB hetero- and homodimers, which, in turn, drive iNOS expression and support melanoma tumorigenesis.

  5. Electron pitch angle diffusion by electrostatic electron cyclotron harmonic waves: The origin of pancake distributions

    NASA Astrophysics Data System (ADS)

    Horne, Richard B.; Thorne, Richard M.

    2000-03-01

    It has been suggested that highly anisotropic electron pancake distributions are the result of pitch angle diffusion by electrostatic electron cyclotron harmonic (ECH) and whistler mode waves in the equatorial region. Here we present pitch angle diffusion rates for ECH wave spectra centered at different frequencies with respect to the electron gyrofrequency Ωe corresponding to spacecraft observations. The wave spectra are carefully mapped to the correct resonant electron velocities. We show that previous diffusion calculations of ECH waves at 1.5Ωe, driven by the loss cone instability, result in large diffusion rates confined to a small range of pitch angles near the loss cone and therefore cannot account for pancake distributions. However, when the wave spectrum is centered at higher frequencies in the band (>1.6Ωe), the diffusion rates become very small inside the loss cone, peak just outside, and remain large over a wide range of pitch angles up to 60° or more. When the upper hybrid resonance frequency ωUHR is several times Ωe, ECH waves excited in higher bands also contribute significantly to pitch angle diffusion outside the loss cone up to very large pitch angles. We suggest that ECH waves driven by a loss cone could form pancake distributions as they grow if the wave spectrum extends from the middle to the upper part of the first (and higher) gyroharmonic bands. Alternatively, we suggest that pancake distributions can be formed by outward propagation in a nonhomogeneous medium, so that resonant absorption occurs at higher frequencies between(n+12) and (n+1)Ωe in regions where waves are also growing locally at <=1.5Ωe. The calculated diffusion rates suggest that ECH waves with amplitudes of the order of 1 mV m-1 can form pancake distributions from an initially isotropic distribution on a timescale of a few hours. This is consistent with recent CRRES observations of

  6. Spectral geometry of {kappa}-Minkowski space

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    D'Andrea, Francesco

    After recalling Snyder's idea [Phys. Rev. 71, 38 (1947)] of using vector fields over a smooth manifold as 'coordinates on a noncommutative space', we discuss a two-dimensional toy-model whose 'dual' noncommutative coordinates form a Lie algebra: this is the well-known {kappa}-Minkowski space [Phys. Lett. B 334, 348 (1994)]. We show how to improve Snyder's idea using the tools of quantum groups and noncommutative geometry. We find a natural representation of the coordinate algebra of {kappa}-Minkowski as linear operators on an Hilbert space (a major problem in the construction of a physical theory), study its 'spectral properties', and discuss how tomore » obtain a Dirac operator for this space. We describe two Dirac operators. The first is associated with a spectral triple. We prove that the cyclic integral of Dimitrijevic et al. [Eur. Phys. J. C 31, 129 (2003)] can be obtained as Dixmier trace associated to this triple. The second Dirac operator is equivariant for the action of the quantum Euclidean group, but it has unbounded commutators with the algebra.« less

  7. Ordovician and Silurian Phi Kappa and Trail Creek formations, Pioneer Mountains, central Idaho; stratigraphic and structural revisions, and new data on graptolite faunas

    USGS Publications Warehouse

    Dover, James H.; Berry, William B.N.; Ross, Reuben James

    1980-01-01

    Recent geologic mapping in the northern Pioneer Mountains combined with the identification of graptolites from 116 new collections indicate that the Ordovician and Silurian Phi Kappa and Trail Creek Formations occur in a series of thrust-bounded slices within a broad zone of imbricate thrust faulting. Though confirming a deformational style first reported in a 1963 study by Michael Churkin, our data suggest that the complexity and regional extent of the thrust zone were not previously recognized. Most previously published sections of the Phi Kappa and Trail Creek Formations were measured across unrecognized thrust faults and therefore include not only structural repetitions of graptolitic Ordovician and Silurian rocks but also other tectonically juxtaposed lithostratigraphic units of diverse ages as well. Because of this discovery, the need to reconsider the stratigraphic validity of these formations and their lithology, nomenclature, structural distribution, facies relations, and graptolite faunas has arisen. The Phi Kappa Formation in most thrust slices has internal stratigraphic continuity despite the intensity of deformation to which it was subjected. As revised herein, the Phi Kappa Formation is restricted to a structurally repeated succession of predominantly black, carbonaceous, graptolitic argillite and shale. Some limy, light-gray-weathering shale occurs in the middle part of the section, and fine-grained locally pebbly quartzite is present at the base. The basal quartzite is here named the Basin Gulch Quartzite Member of the Phi Kappa. The Phi Kappa redefined on a lithologic basis represents the span of Ordovician time from W. B. N. Berry's graptolite zones 2-4 through 15 and also includes approximately 17 m of lithologically identical shale of Early and Middle Silurian age at the top. The lower contact of the formation as revised is tectonic. The Phi Kappa is gradationally overlain by the Trail Creek Formation as restricted herein. Most of the coarser

  8. Chlamydia pneumoniae activates IKK/I kappa B-mediated signaling, which is inhibited by 4-HNE and following primary exposure.

    PubMed

    Donath, Bernadette; Fischer, Claudia; Page, Sharon; Prebeck, Sigrid; Jilg, Nikolaus; Weber, Marion; da Costa, Clarissa; Neumeier, Dieter; Miethke, Thomas; Brand, Korbinian

    2002-11-01

    Chlamydia pneumoniae may be involved in atherosclerosis by inducing inflammation as well as LDL oxidation. The transcription factor NF-kappa B is found in an active state in atherosclerotic lesions. This study examined the effect of C. pneumoniae exposure on the NF-kappa B system in human monocytic lineage cells. Short exposure to C. pneumoniae as well as chlamydial heat shock protein 60 activated NF-kappa B, accompanied by increased cytokine production. Incubation with C. pneumoniae-induced depletion of I kappa B-alpha and later I kappa B-epsilon which was preceded by I kappa B kinase complex activation. 4-Hydroxynonenal, an aldehyde LDL oxidation product, was shown to inhibit C. pneumoniae induced NF-kappa B activation by preventing I kappa B phosphorylation/proteolysis. During long-term incubation with C. pneumoniae I kappa B-alpha returned to baseline, whereas the levels of I kappa B-epsilon and p65 were upregulated. Interestingly, long-term preincubation with C. pneumoniae selectively prevented restimulation by this microorganism, which appears to be at least partly facilitated by inhibition of I kappa B proteolysis. C. pneumoniae-induced NF-kappa B activation as well as the inhibition of that effect under certain conditions may contribute to chronic inflammation with potential relevance to vascular disease.

  9. Cylindrical ion-acoustic solitary waves in electronegative plasmas with superthermal electrons

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Eslami, Parvin; Mottaghizadeh, Marzieh

    2012-06-15

    By using the standard reductive perturbation technique, a three-dimensional cylindrical Kadomtsev-Petviashvili equation (CKPE), which governs the dynamics of ion acoustic solitary waves (IASWs), is derived for small but finite amplitude ion-acoustic waves in cylindrical geometry in a collisionless unmagnetized plasma with kappa distributed electrons, thermal positrons, and cold ions. The generalized expansion method is used to solve analytically the CKPE. The existence regions of localized pulses are investigated. It is found that the solution of the CKPE supports only compressive solitary waves. Furthermore, the effects of superthermal electrons, the ratio of the electron temperature to positron temperature, the ratio ofmore » the positron density to electron density and direction cosine of the wave propagation on the profiles of the amplitudes, and widths of the solitary structures are examined numerically. It is shown these parameters play a vital role in the formation of ion acoustic solitary waves.« less

  10. Reinstatement of cocaine place-conditioning prevented by the peptide kappa-opioid receptor antagonist arodyn.

    PubMed

    Carey, A N; Borozny, K; Aldrich, J V; McLaughlin, J P

    2007-08-13

    Stress contributes to the reinstatement of cocaine-seeking behavior in abstinent subjects. Kappa-opioid receptor antagonists attenuate the behavioral effects of stress, potentially providing therapeutic value in treating cocaine abuse. Presently, the peptide arodyn produced long-lasting kappa-opioid receptor antagonism, suppressing kappa-opioid receptor agonist-induced antinociception at least 3 days after intracerebroventricular administration of 0.3 nmol. C57Bl/6J mice demonstrated cocaine-conditioned place preference, extinction over 3 weeks, and a subsequent reinstatement of place preference. Arodyn pretreatment suppressed stress-induced, but not cocaine-exposed, reinstatement of cocaine place preference. These results verify that arodyn and other kappa-opioid receptor antagonists may be useful therapeutics for cocaine abuse.

  11. Human placenta: relative content of antibodies of different classes and subclasses (IgG1-IgG4) containing lambda- and kappa-light chains and chimeric lambda-kappa-immunoglobulins.

    PubMed

    Lekchnov, Evgenii A; Sedykh, Sergey E; Dmitrenok, Pavel S; Buneva, Valentina N; Nevinsky, Georgy A

    2015-06-01

    The specific organ placenta is much more than a filter: it is an organ that protects, feeds and regulates the growth of the embryo. Affinity chromatography, ELISA, SDS-PAGE and matrix-assisted laser desorption ionization mass spectrometry were used. Using 10 intact human placentas deprived of blood, a quantitative analysis of average relative content [% of total immunoglobulins (Igs)] was carried out for the first time: (92.7), IgA (2.4), IgM (2.5), kappa-antibodies (51.4), lambda-antibodies (48.6), IgG1 (47.0), IgG2 (39.5), IgG3 (8.8) and IgG4 (4.3). It was shown for the first time that placenta contains sIgA (2.5%). In the classic paradigm, Igs represent products of clonal B-cell populations, each producing antibodies recognizing a single antigen. There is a common belief that IgGs in mammalian biological fluids are monovalent molecules having stable structures and two identical antigen-binding sites. However, similarly to human milk Igs, placenta antibodies undergo extensive half-molecule exchange and the IgG pool consists of 43.5 ± 15.0% kappa-kappa-IgGs and 41.6 ± 17.0% lambda-lambda-IgGs, while 15.0 ± 4.0% of the IgGs contained both kappa- and lambda-light chains. Kappa-kappa-IgGs and lambda-lambda-IgGs contained, respectively (%): IgG1 (47.7 and 34.4), IgG2 (36.3 and 44.5), IgG3 (7.4 and 11.8) and IgG4 (7.5 and 9.1), while chimeric kappa-lambda-IgGs consisted of (%): 43.5 IgG1, 41.0 IgG2, 5.6 IgG3 and 7.9 IgG4. Our data are indicative of the possibility of half-molecule exchange between placenta IgGs of various subclasses, raised against different antigens, which explains a very well-known polyspecificity and cross-reactivity of different human IgGs. © The Japanese Society for Immunology. 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Suprathermal electron loss cone distributions in the solar wind: Ulysses observations

    NASA Technical Reports Server (NTRS)

    Phillips, J. L.; Feldman, W. C.; Gosling, J. T.; Hammond, C. M.; Forsyth, R. J.

    1995-01-01

    Solar wind suprathermal electron distributions in the solar wind generally carry a field-aligned antisunward heat flux. Within coronal mass ejections and upstream of strong shocks driven by corotating interaction regions (CIRs), counterstreaming electron beams are observed. We present observations by the Ulysses solar wind plasma experiment of a new class of suprathermal electron signatures. At low solar latitudes and heliocentric distances beyond 3.5 AU Ulysses encountered several intervals, ranging in duration from 1 hour to 22 hours, in which the suprathermal distributions included an antisunward field-aligned beam and a return population with a flux dropout typically spanning +/- 60 deg from the sunward field-aligned direction. All events occurred within CIRs, downstream of the forward and reverse shocks or waves bounding the interaction regions. We evaluate the hypothesis that the sunward-moving electrons result from reflection of the antisunward beams at magnetic field compressions downstream from the observations, with wide loss cones caused by the relatively weak compression ratio. This hypothesis requires that field magnitude within the CIRs actually increase with increasing field-aligned distance from the Sun. Details of the electron distributions and ramifications for CIR and shock geometry will be presented.

  13. Dynamics of the spatial electron density distribution of EUV-induced plasmas

    NASA Astrophysics Data System (ADS)

    van der Horst, R. M.; Beckers, J.; Osorio, E. A.; Banine, V. Y.

    2015-11-01

    We studied the temporal evolution of the electron density distribution in a low pressure pulsed plasma induced by high energy extreme ultraviolet (EUV) photons using microwave cavity resonance spectroscopy (MCRS). In principle, MCRS only provides space averaged information about the electron density. However, we demonstrate here the possibility to obtain spatial information by combining multiple resonant modes. It is shown that EUV-induced plasmas, albeit being a rather exotic plasma, can be explained by known plasma physical laws and processes. Two stages of plasma behaviour are observed: first the electron density distribution contracts, after which it expands. It is shown that the contraction is due to cooling of the electrons. The moment when the density distribution starts to expand is related to the inertia of the ions. After tens of microseconds, the electrons reached the wall of the cavity. The speed of this expansion is dependent on the gas pressure and can be divided into two regimes. It is shown that the acoustic dominated regime the expansion speed is independent of the gas pressure and that in the diffusion dominated regime the expansion depends reciprocal on the gas pressure.

  14. Inverse expression of estrogen receptor-beta and nuclear factor-kappaB in urinary bladder carcinogenesis.

    PubMed

    Kontos, Stylianos; Kominea, Athina; Melachrinou, Maria; Balampani, Eleni; Sotiropoulou-Bonikou, Georgia

    2010-09-01

    To investigate the expression of nuclear factor-kappaB (NF-kappaB) and estrogen receptor-beta (ER-beta) signalling pathways in bladder urothelial carcinoma according to clinicopathological features, in order to elucidate their role during carcinogenesis. Immunohistochemical methodology was carried out on formalin-fixed, paraffin-embedded sections from urinary bladder carcinomas of 140 patients (94 males and 46 females) who underwent transurethral resection of bladder neoplasms. Correlations between ER-beta and NF-kappaB, and tumor grade and T-stage were evaluated, along with demographic data, sex and age. A significant decrease in ER-beta expression in the nucleus of bladder cells during loss of cell differentiation (r(s) = -0.61, P-value < 0.001, test of trend P-value = 0.003) and in muscle invasive carcinomas (T2-T4; test of trend P-value < 0.001) was found. p65 Subunit of NF-kappaB was expressed in the nucleus and in the cytoplasm of bladder epithelial cells. A strong positive association between tumor grade and nuclear expression of NF-kappaB was shown. No correlation between NF-kappaB, nuclear or cytoplasmic staining, with T-stage was observed. An inverse correlation between ER-beta and nuclear p65 immunoreactivity was observed (r(s) = -0.45, P-value < 0.001). There was no correlation with demographic data. Our immunohistochemical study suggests the possible inverse regulation of NF-kappaB and ER-beta transcription factor during bladder carcinogenesis. Selective ER-beta agonists and agents, inhibitors of NF-kappaB, might represent a possible new treatment strategy for bladder urothelial tumors.

  15. NF-{kappa}B p65 represses {beta}-catenin-activated transcription of cyclin D1

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hwang, Injoo; Choi, Yong Seok; Jeon, Mi-Ya

    2010-12-03

    Research highlights: {yields} Cyclin D1 transcription is directly activated by {beta}-catenin; however, {beta}-catenin-induced cyclin D1 transcription is reduced by NF-{kappa}B p65. {yields} Protein-protein interaction between NF-{kappa}B p65 and {beta}-catenin might be responsible for p65-mediated repression of cyclin D1. {yields} One of five putative binding sites, located further upstream of other sites, is the major {beta}-catenin binding site in the cyclin D1 promoter. {yields} NF-{kappa}B binding site in cyclin D1 is occupied not only by p65 but also by {beta}-catenin, which is dynamically regulated by the signal. -- Abstract: Signaling crosstalk between the {beta}-catenin and NF-{kappa}B pathways represents a functional network.more » To test whether the crosstalk also occurs on their common target genes, the cyclin D1 promoter was used as a model because it contains binding sites for both proteins. {beta}-catenin activated transcription from the cyclin D1 promoter, while co-expression of NF-{kappa}B p65 reduced {beta}-catenin-induced transcription. Chromatin immunoprecipitation revealed lithium chloride-induced binding of {beta}-catenin on one of the T-cell activating factor binding sites. More interestingly, {beta}-catenin binding was greatly reduced by NF-{kappa}B p65, possibly by the protein-protein interaction between the two proteins. Such a dynamic and complex binding of {beta}-catenin and NF-{kappa}B on promoters might contribute to the regulated expression of their target genes.« less

  16. Solar wind ∼0.1-1.5 keV electrons at quiet times

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tao, Jiawei; Wang, Linghua, E-mail: wanglhwang@gmail.com; Zong, Qiugang

    2016-03-25

    We present a statistical survey of the energy spectrum of solar wind suprathermal (∼0.1-1.5 keV) electrons measured by the WIND 3-D Plasma & Energetic Particle (3DP) instrument at 1 AU during quiet times at the minimum and maximum of solar cycles 23 and 24. Firstly, we separate strahl (beaming) electrons and halo (isotropic) electrons based on their features in pitch angle distributions. Secondly, we fit the observed energy spectrum of both the strahl and halo electrons at ∼0.1-1.5 keV to a Kappa distribution function with an index κ, effective temperature T{sub eff} and density n{sub 0}. We also integrate themore » the measurements over ∼0.1-1.5 keV to obtain the average electron energy E{sub avg} of the strahl and halo. We find a strong positive correlation between κ and T{sub eff} for both the strahl and halo, possibly reflecting the nature of the generation of these suprathermal electrons. Among the 245 selected samples, ∼68% have the halo κ smaller than the strahl κ, while ∼50% have the halo E{sub h} larger than the strahl E{sub s}.« less

  17. Electron energy distributions in uranium helium mixtures. M.S. Thesis

    NASA Technical Reports Server (NTRS)

    Makowski, M. A.

    1977-01-01

    The high energy portion of the electron energy distribution for mixtures of uranium and helium at 1 atm, 5000 K, and a neutron flux of 2x10 to the 12th power/sq cm-sec have been calculated. The addition of He improves the heat transport characteristics of the plasma and has the feature that the He energy levels lie in the high energy portion of the electron distribution, potentially allowing non maxwellian excitation. It is concluded, however, that the resulting reaction rates are marginal relative to achieving inversion in He.

  18. Monte Carlo calculations of energy deposition distributions of electrons below 20 keV in protein.

    PubMed

    Tan, Zhenyu; Liu, Wei

    2014-05-01

    The distributions of energy depositions of electrons in semi-infinite bulk protein and the radial dose distributions of point-isotropic mono-energetic electron sources [i.e., the so-called dose point kernel (DPK)] in protein have been systematically calculated in the energy range below 20 keV, based on Monte Carlo methods. The ranges of electrons have been evaluated by extrapolating two calculated distributions, respectively, and the evaluated ranges of electrons are compared with the electron mean path length in protein which has been calculated by using electron inelastic cross sections described in this work in the continuous-slowing-down approximation. It has been found that for a given energy, the electron mean path length is smaller than the electron range evaluated from DPK, but it is large compared to the electron range obtained from the energy deposition distributions of electrons in semi-infinite bulk protein. The energy dependences of the extrapolated electron ranges based on the two investigated distributions are given, respectively, in a power-law form. In addition, the DPK in protein has also been compared with that in liquid water. An evident difference between the two DPKs is observed. The calculations presented in this work may be useful in studies of radiation effects on proteins.

  19. Formation of energetic electron butterfly distributions by magnetosonic waves via Landau resonance

    DOE PAGES

    Li, Jinxing; Ni, Binbin; Ma, Qianli; ...

    2016-03-06

    Radiation belt electrons can exhibit different types of pitch angle distributions in response to various magnetospheric processes. Butterfly distributions, characterized by flux minima at pitch angles around 90°, are broadly observed in both the outer and inner belts and the slot region. Butterfly distributions close to the outer magnetospheric boundary have been attributed to drift shell splitting and losses to the magnetopause. However, their occurrence in the inner belt and the slot region has hitherto not been resolved. In this study, by analyzing the particle and wave data collected by the Van Allen Probes during a geomagnetic storm, we combinemore » test particle calculations and Fokker-Planck simulations to reveal that scattering by equatorial magnetosonic waves is a significant cause for the formation of energetic electron butterfly distributions in the inner magnetosphere. Finally, another event shows that a large-amplitude magnetosonic wave in the outer belt can create electron butterfly distributions in just a few minutes.« less

  20. Peripheral kappa-opioid agonist, ICI 204448, evokes hypothermia in cold-exposed rats.

    PubMed

    Rawls, Scott M; Ding, Zhe; Gray, Alex M; Cowan, Alan

    2005-05-01

    ICI 204448, a selective kappa-opioid agonist with limited CNS access, can be used to discriminate central and peripheral opioid actions on physiological systems such as pain and thermoregulation. Therefore, we investigated the effect of ICI 204448 (2.5, 5, and 10 mg/kg, s.c.) on male Sprague-Dawley rats exposed to ambient temperatures of 5, 20, or 32 degrees C. ICI 204448 did not alter the body temperature of rats maintained at 20 or 32 degrees C. However, 5 and 10 mg/kg of ICI 204448 evoked significant hypothermia in rats exposed to 5 degrees C. The i.c.v. administration of nor-BNI, a kappa-opioid antagonist, did not affect the hypothermia produced by the systemic injection of ICI 204448. Thus, an involvement of brain kappa-opioid receptors in ICI 204448-evoked hypothermia is unlikely. The present data demonstrate for the first time that ICI 204448 produces hypothermia in cold-exposed rats and suggest that the role of peripheral kappa-opioid receptors in thermoregulation becomes more significant at cold ambient temperatures. Copyright (c) 2005 S. Karger AG, Basel.

  1. Colloidal gas-liquid condensation of polystyrene latex particles with intermediate kappa a values (5 to 160, a > kappa(-1)).

    PubMed

    Ishikawa, Masamichi; Kitano, Ryota

    2010-02-16

    Polystyrene latex particles showed gas-liquid condensation under the conditions of large particle radius (a > kappa(-1)) and intermediate kappa a, where kappa is the Debye-Hückel parameter and a is the particle radius. The particles were dissolved in deionized water containing ethanol from 0 to 77 vol %, settled to the bottom of the glass plate within 1 h, and then laterally moved toward the center of a cell over a 20 h period in reaching a state of equilibrium condensation. All of the suspensions that were 1 and 3 microm in diameter and 0.01-0.20 vol % in concentration realized similar gas-liquid condensation with clear gas-liquid boundaries. In 50 vol % ethanol solvent, additional ethanol was added to enhance the sedimentation force so as to restrict the particles in a monoparticle layer thickness. The coexistence of gas-liquid-solid (crystalline solid) was microscopically recognized from the periphery to the center of the condensates. A phase diagram of the gas-liquid condensation was created as a function of KCl concentration at a particle diameter of 3 microm, 0.10 vol % concentration, and 50:50 water/ethanol solvent at room temperature. The miscibility gap was observed in the concentration range from 1 to 250 microM. There was an upper limit of salt concentration where the phase separation disappeared, showing nearly critical behavior of macroscopic density fluctuation from 250 microM to 1 mM. These results add new experimental evidence to the existence of colloidal gas-liquid condensation and specify conditions of like-charge attraction between particles.

  2. Synergistic chondroprotective effects of curcumin and resveratrol in human articular chondrocytes: inhibition of IL-1beta-induced NF-kappaB-mediated inflammation and apoptosis.

    PubMed

    Csaki, Constanze; Mobasheri, Ali; Shakibaei, Mehdi

    2009-01-01

    Currently available treatments for osteoarthritis (OA) are restricted to nonsteroidal anti-inflammatory drugs, which exhibit numerous side effects and are only temporarily effective. Thus novel, safe and more efficacious anti-inflammatory agents are needed for OA. Naturally occurring polyphenolic compounds, such as curcumin and resveratrol, are potent agents for modulating inflammation. Both compounds mediate their effects by targeting the NF-kappaB signalling pathway. We have recently demonstrated that in chondrocytes resveratrol modulates the NF-kappaB pathway by inhibiting the proteasome, while curcumin modulates the activation of NF-kappaB by inhibiting upstream kinases (Akt). However, the combinational effects of these compounds in chondrocytes has not been studied and/or compared with their individual effects. The aim of this study was to investigate the potential synergistic effects of curcumin and resveratrol on IL-1beta-stimulated human chondrocytes in vitro using immunoblotting and electron microscopy. Treatment with curcumin and resveratrol suppressed NF-kappaB-regulated gene products involved in inflammation (cyclooxygenase-2, matrix metalloproteinase (MMP)-3, MMP-9, vascular endothelial growth factor), inhibited apoptosis (Bcl-2, Bcl-xL, and TNF-alpha receptor-associated factor 1) and prevented activation of caspase-3. IL-1beta-induced NF-kappaB activation was suppressed directly by cocktails of curcumin and resveratrol through inhibition of Ikappakappa and proteasome activation, inhibition of IkappaBalpha phosphorylation and degradation, and inhibition of nuclear translocation of NF-kappaB. The modulatory effects of curcumin and resveratrol on IL-1beta-induced expression of cartilage specific matrix and proinflammatory enzymes were mediated in part by the cartilage-specific transcription factor Sox-9. We propose that combining these natural compounds may be a useful strategy in OA therapy as compared with separate treatment with each individual

  3. Characterizing and Optimizing Photocathode Laser Distributions for Ultra-low Emittance Electron Beam Operations

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhou, F.; Bohler, D.; Ding, Y.

    2015-12-07

    Photocathode RF gun has been widely used for generation of high-brightness electron beams for many different applications. We found that the drive laser distributions in such RF guns play important roles in minimizing the electron beam emittance. Characterizing the laser distributions with measurable parameters and optimizing beam emittance versus the laser distribution parameters in both spatial and temporal directions are highly desired for high-brightness electron beam operation. In this paper, we report systematic measurements and simulations of emittance dependence on the measurable parameters represented for spatial and temporal laser distributions at the photocathode RF gun systems of Linac Coherent Lightmore » Source. The tolerable parameter ranges for photocathode drive laser distributions in both directions are presented for ultra-low emittance beam operations.« less

  4. A note on dust grain charging in space plasmas

    NASA Technical Reports Server (NTRS)

    Rosenberg, M.; Mendis, D. A.

    1992-01-01

    Central to the study of dust-plasma interactions in the solar system is the electrostatic charging of dust grains. While previous calculations have generally assumed that the distributions of electrons and ions in the plasma are Maxwellian, most space plasmas are observed to have non-Maxwellian tails and can often be fit by a generalized Lorentzian (kappa) distribution. Here we use such a distribution to reevaluate the grain potential, under the condition that the dominant currents to the grain are due to electron and ion collection, as is the case in certain regions of space. The magnitude of the grain potential is found to be larger than that in a Maxwellian plasma as long as the electrons are described by a kappa distribution: this enhancement increased with ion mass and decreasing electron kappa. The modification of the grain potential in generalized Lorentzian plasmas has implications for both the physics (e.g., grain growth and disruption) and the dynamics of dust in space plasmas. These are also briefly discussed.

  5. GS143, an I{kappa}B ubiquitination inhibitor, inhibits allergic airway inflammation in mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hirose, Koichi; Wakashin, Hidefumi; Oki, Mie

    2008-09-26

    Asthma is characterized by airway inflammation with intense eosinophil infiltration and mucus hyper-production, in which antigen-specific Th2 cells play critical roles. Nuclear factor-{kappa}B (NF-{kappa}B) pathway has been demonstrated to be essential for the production of Th2 cytokines and chemokines in the airways in murine asthma models. In the present study, we examined the effect of GS143, a novel small-molecule inhibitor of I{kappa}B ubiquitination, on antigen-induced airway inflammation and Th2 cytokine production in mice. Intranasal administration of GS143 prior to antigen challenge suppressed antigen-induced NF-{kappa}B activation in the lung of sensitized mice. Intranasal administration of GS143 also inhibited antigen-induced eosinophil andmore » lymphocyte recruitment into the airways as well as the expression of Th2 cytokines and eotaxin in the airways. Moreover, GS143 inhibited antigen-induced differentiation of Th2 cells but not of Th1 cells in vitro. Taken together, these results suggest that I{kappa}B ubiquitination inhibitor may have therapeutic potential against asthma.« less

  6. A note on the kappa statistic for clustered dichotomous data.

    PubMed

    Zhou, Ming; Yang, Zhao

    2014-06-30

    The kappa statistic is widely used to assess the agreement between two raters. Motivated by a simulation-based cluster bootstrap method to calculate the variance of the kappa statistic for clustered physician-patients dichotomous data, we investigate its special correlation structure and develop a new simple and efficient data generation algorithm. For the clustered physician-patients dichotomous data, based on the delta method and its special covariance structure, we propose a semi-parametric variance estimator for the kappa statistic. An extensive Monte Carlo simulation study is performed to evaluate the performance of the new proposal and five existing methods with respect to the empirical coverage probability, root-mean-square error, and average width of the 95% confidence interval for the kappa statistic. The variance estimator ignoring the dependence within a cluster is generally inappropriate, and the variance estimators from the new proposal, bootstrap-based methods, and the sampling-based delta method perform reasonably well for at least a moderately large number of clusters (e.g., the number of clusters K ⩾50). The new proposal and sampling-based delta method provide convenient tools for efficient computations and non-simulation-based alternatives to the existing bootstrap-based methods. Moreover, the new proposal has acceptable performance even when the number of clusters is as small as K = 25. To illustrate the practical application of all the methods, one psychiatric research data and two simulated clustered physician-patients dichotomous data are analyzed. Copyright © 2014 John Wiley & Sons, Ltd.

  7. High Agreement and High Prevalence: The Paradox of Cohen's Kappa.

    PubMed

    Zec, Slavica; Soriani, Nicola; Comoretto, Rosanna; Baldi, Ileana

    2017-01-01

    Cohen's Kappa is the most used agreement statistic in literature. However, under certain conditions, it is affected by a paradox which returns biased estimates of the statistic itself. The aim of the study is to provide sufficient information which allows the reader to make an informed choice of the correct agreement measure, by underlining some optimal properties of Gwet's AC1 in comparison to Cohen's Kappa, using a real data example. During the process of literature review, we have asked a panel of three evaluators to come up with a judgment on the quality of 57 randomized controlled trials assigning a score to each trial using the Jadad scale. The quality was evaluated according to the following dimensions: adopted design, randomization unit, type of primary endpoint. With respect to each of the above described features, the agreement between the three evaluators has been calculated using Cohen's Kappa statistic and Gwet's AC1 statistic and, finally, the values have been compared with the observed agreement. The values of the Cohen's Kappa statistic would lead to believe that the agreement levels for the variables Unit, Design and Primary Endpoints are totally unsatisfactory. The AC1 statistic, on the contrary, shows plausible values which are in line with the respective values of the observed concordance. We conclude that it would always be appropriate to adopt the AC1 statistic, thus bypassing any risk of incurring the paradox and drawing wrong conclusions about the results of agreement analysis.

  8. Physical mechanism causing rapid changes in ultrarelativistic electron pitch angle distributions right after a shock arrival: Evaluation of an electron dropout event

    NASA Astrophysics Data System (ADS)

    Zhang, X.-J.; Li, W.; Thorne, R. M.; Angelopoulos, V.; Ma, Q.; Li, J.; Bortnik, J.; Nishimura, Y.; Chen, L.; Baker, D. N.; Reeves, G. D.; Spence, H. E.; Kletzing, C. A.; Kurth, W. S.; Hospodarsky, G. B.; Blake, J. B.; Fennell, J. F.

    2016-09-01

    Three mechanisms have been proposed to explain relativistic electron flux depletions (dropouts) in the Earth's outer radiation belt during storm times: adiabatic expansion of electron drift shells due to a decrease in magnetic field strength, magnetopause shadowing and subsequent outward radial diffusion, and precipitation into the atmosphere (driven by EMIC wave scattering). Which mechanism predominates in causing electron dropouts commonly observed in the outer radiation belt is still debatable. In the present study, we evaluate the physical mechanism that may be primarily responsible for causing the sudden change in relativistic electron pitch angle distributions during a dropout event observed by Van Allen Probes during the main phase of the 27 February 2014 storm. During this event, the phase space density of ultrarelativistic (>1 MeV) electrons was depleted by more than 1 order of magnitude over the entire radial extent of the outer radiation belt (3 < L* < 5) in less than 6 h after the passage of an interplanetary shock. We model the electron pitch angle distribution under a compressed magnetic field topology based on actual solar wind conditions. Although these ultrarelativistic electrons exhibit highly anisotropic (peaked in 90°), energy-dependent pitch angle distributions, which appear to be associated with the typical EMIC wave scattering, comparison of the modeled electron distribution to electron measurements indicates that drift shell splitting is responsible for this rapid change in electron pitch angle distributions. This further indicates that magnetopause loss is the predominant cause of the electron dropout right after the shock arrival.

  9. Integrated Nationwide Electronic Health Records system: Semi-distributed architecture approach.

    PubMed

    Fragidis, Leonidas L; Chatzoglou, Prodromos D; Aggelidis, Vassilios P

    2016-11-14

    The integration of heterogeneous electronic health records systems by building an interoperable nationwide electronic health record system provides undisputable benefits in health care, like superior health information quality, medical errors prevention and cost saving. This paper proposes a semi-distributed system architecture approach for an integrated national electronic health record system incorporating the advantages of the two dominant approaches, the centralized architecture and the distributed architecture. The high level design of the main elements for the proposed architecture is provided along with diagrams of execution and operation and data synchronization architecture for the proposed solution. The proposed approach effectively handles issues related to redundancy, consistency, security, privacy, availability, load balancing, maintainability, complexity and interoperability of citizen's health data. The proposed semi-distributed architecture offers a robust interoperability framework without healthcare providers to change their local EHR systems. It is a pragmatic approach taking into account the characteristics of the Greek national healthcare system along with the national public administration data communication network infrastructure, for achieving EHR integration with acceptable implementation cost.

  10. Whistler Waves With Electron Temperature Anisotropy And Non-Maxwellian Distribution Functions

    NASA Astrophysics Data System (ADS)

    Masood, W.

    2017-12-01

    Low frequency waves (˜ 100Hz), popularly known as Lion roars, are ubiquitously observed by satellites in terrestrial magnetosheath. By dint of both wave and electron data from the Cluster spacecraft and employing the linear kinetic theory for the electromagnetic waves, Masood et. al. (Ann. Geophysicae. 24, 1725-1735 (2006)) examined the conjecture made by Thorne and Tsurutani (Nature, 93, 384 (1981)) that whistler waves with electron temperature anisotropy are the progenitors of lion roars. It turned out that the study based upon the bi-Maxwellian distribution function did not come up with a satisfactory explanation of certain disagreements between theory and data. In this paper, we revisit the problem using the generalized (r, q) distribution to carry out the linear stability analysis. It is shown that good qualitative and quantitative agreements are found between theory and data using this distribution. Whistler waves with electron temperature anisotropy are also investigated with other non-Maxwellian distribution functions and general comparison is made in the end and differences in each case are highlighted. The possible applications in space plasmas are also pointed out.

  11. Kappa and Rater Accuracy: Paradigms and Parameters

    ERIC Educational Resources Information Center

    Conger, Anthony J.

    2017-01-01

    Drawing parallels to classical test theory, this article clarifies the difference between rater accuracy and reliability and demonstrates how category marginal frequencies affect rater agreement and Cohen's kappa. Category assignment paradigms are developed: comparing raters to a standard (index) versus comparing two raters to one another…

  12. Hydromagnetic Waves and Instabilities in Kappa Distribution Plasma

    DTIC Science & Technology

    2009-01-01

    perpendicular effective particle temperatures, respec- tively. Two other parameters related to pM and pnl which naturally occur in the study of...role in determin- ing the excitation conditions of the field swelling and mirror instabilities [see Eqs. (60) and (65)]. Calculating pnl /pni from Eq...more convenient form of the perturbed distribution function /„ that may be used in- stead of Eq. (12) to obtain nn, pM, and pnl given by Eqs. (72

  13. Characteristics of electron distributions observed during large amplitude whistler wave events in the magnetosphere

    NASA Astrophysics Data System (ADS)

    Wilson, L. B., III; Cattell, C. A.; Kellogg, P. J.; Goetz, K.; Wygant, J.; Breneman, A. W.; Kersten, K.

    2010-12-01

    We present a statistical study of the characteristics of electron distributions associated with large amplitude whistler waves inside the terrestrial magnetosphere using waveform capture data as an addition of the study by Kellogg et al., [2010b]. We identified three types of electron distributions observed simultaneously with the whistler waves including beam-like, beam/flattop, and anisotropic distributions. The whistlers exhibited different characteristics dependent upon the observed electron distributions. The majority of the waveforms observed in our study have f/fce ≤ 0.5 and are observed primarily in the radiation belts outside the plasmapause simultaneously with anisotropic electron distributions. We also present an example waveform capture of the largest magnetic field amplitude (≥ 8 nT pk-pk) whistler wave measured in the radiation belts. The majority of the largest amplitude whistlers occur during magnetically active periods (AE > 200 nT).

  14. Characteristics of Electron Distributions Observed During Large Amplitude Whistler Wave Events in the Magnetosphere

    NASA Technical Reports Server (NTRS)

    Wilson, Lynn B., III

    2010-01-01

    We present a statistical study of the characteristics of electron distributions associated with large amplitude whistler waves inside the terrestrial magnetosphere using waveform capture data as an addition of the study by Kellogg et al., [2010b]. We identified three types of electron distributions observed simultaneously with the whistler waves including beam-like, beam/flattop, and anisotropic distributions. The whistlers exhibited different characteristics dependent upon the observed electron distributions. The majority of the waveforms observed in our study have f/fce < or = 0.5 and are observed primarily in the radiation belts outside the plasmapause simultaneously with anisotropic electron distributions. We also present an example waveform capture of the largest magnetic field amplitude (> or = 8 nT pk-pk) whistler wave measured in the radiation belts. The majority of the largest amplitude whistlers occur during magnetically active periods (AE > 200 nT).

  15. Significant Differences in Physicochemical Properties of Human Immunoglobulin Kappa and Lambda CDR3 Regions.

    PubMed

    Townsend, Catherine L; Laffy, Julie M J; Wu, Yu-Chang Bryan; Silva O'Hare, Joselli; Martin, Victoria; Kipling, David; Fraternali, Franca; Dunn-Walters, Deborah K

    2016-01-01

    Antibody variable regions are composed of a heavy and a light chain, and in humans, there are two light chain isotypes: kappa and lambda. Despite their importance in receptor editing, the light chain is often overlooked in the antibody literature, with the focus being on the heavy chain complementarity-determining region (CDR)-H3 region. In this paper, we set out to investigate the physicochemical and structural differences between human kappa and lambda light chain CDR regions. We constructed a dataset containing over 29,000 light chain variable region sequences from IgM-transcribing, newly formed B cells isolated from human bone marrow and peripheral blood. We also used a published human naïve dataset to investigate the CDR-H3 properties of heavy chains paired with kappa and lambda light chains and probed the Protein Data Bank to investigate the structural differences between kappa and lambda antibody CDR regions. We found that kappa and lambda light chains have very different CDR physicochemical and structural properties, whereas the heavy chains with which they are paired do not differ significantly. We also observed that the mean CDR3 N nucleotide addition in the kappa, lambda, and heavy chain gene rearrangements are correlated within donors but can differ between donors. This indicates that terminal deoxynucleotidyl transferase may work with differing efficiencies between different people but the same efficiency in the different classes of immunoglobulin chain within one person. We have observed large differences in the physicochemical and structural properties of kappa and lambda light chain CDR regions. This may reflect different roles in the humoral immune response.

  16. Significant Differences in Physicochemical Properties of Human Immunoglobulin Kappa and Lambda CDR3 Regions

    PubMed Central

    Townsend, Catherine L.; Laffy, Julie M. J.; Wu, Yu-Chang Bryan; Silva O’Hare, Joselli; Martin, Victoria; Kipling, David; Fraternali, Franca; Dunn-Walters, Deborah K.

    2016-01-01

    Antibody variable regions are composed of a heavy and a light chain, and in humans, there are two light chain isotypes: kappa and lambda. Despite their importance in receptor editing, the light chain is often overlooked in the antibody literature, with the focus being on the heavy chain complementarity-determining region (CDR)-H3 region. In this paper, we set out to investigate the physicochemical and structural differences between human kappa and lambda light chain CDR regions. We constructed a dataset containing over 29,000 light chain variable region sequences from IgM-transcribing, newly formed B cells isolated from human bone marrow and peripheral blood. We also used a published human naïve dataset to investigate the CDR-H3 properties of heavy chains paired with kappa and lambda light chains and probed the Protein Data Bank to investigate the structural differences between kappa and lambda antibody CDR regions. We found that kappa and lambda light chains have very different CDR physicochemical and structural properties, whereas the heavy chains with which they are paired do not differ significantly. We also observed that the mean CDR3 N nucleotide addition in the kappa, lambda, and heavy chain gene rearrangements are correlated within donors but can differ between donors. This indicates that terminal deoxynucleotidyl transferase may work with differing efficiencies between different people but the same efficiency in the different classes of immunoglobulin chain within one person. We have observed large differences in the physicochemical and structural properties of kappa and lambda light chain CDR regions. This may reflect different roles in the humoral immune response. PMID:27729912

  17. Resolving runaway electron distributions in space, time, and energy

    NASA Astrophysics Data System (ADS)

    Paz-Soldan, C.; Cooper, C. M.; Aleynikov, P.; Eidietis, N. W.; Lvovskiy, A.; Pace, D. C.; Brennan, D. P.; Hollmann, E. M.; Liu, C.; Moyer, R. A.; Shiraki, D.

    2018-05-01

    Areas of agreement and disagreement with present-day models of runaway electron (RE) evolution are revealed by measuring MeV-level bremsstrahlung radiation from runaway electrons (REs) with a pinhole camera. Spatially resolved measurements localize the RE beam, reveal energy-dependent RE transport, and can be used to perform full two-dimensional (energy and pitch-angle) inversions of the RE phase-space distribution. Energy-resolved measurements find qualitative agreement with modeling on the role of collisional and synchrotron damping in modifying the RE distribution shape. Measurements are consistent with predictions of phase-space attractors that accumulate REs, with non-monotonic features observed in the distribution. Temporally resolved measurements find qualitative agreement with modeling on the impact of collisional and synchrotron damping in varying the RE growth and decay rate. Anomalous RE loss is observed and found to be largest at low energy. Possible roles for kinetic instability or spatial transport to resolve these anomalies are discussed.

  18. Method for rapidly determining a pulp kappa number using spectrophotometry

    DOEpatents

    Chai, Xin-Sheng; Zhu, Jun Yong

    2002-01-01

    A system and method for rapidly determining the pulp kappa number through direct measurement of the potassium permanganate concentration in a pulp-permanganate solution using spectrophotometry. Specifically, the present invention uses strong acidification to carry out the pulp-permanganate oxidation reaction in the pulp-permanganate solution to prevent the precipitation of manganese dioxide (MnO.sub.2). Consequently, spectral interference from the precipitated MnO.sub.2 is eliminated and the oxidation reaction becomes dominant. The spectral intensity of the oxidation reaction is then analyzed to determine the pulp kappa number.

  19. Suprathermal electron energy distribution within the dayside Venus ionosphere

    NASA Technical Reports Server (NTRS)

    Knudsen, W. C.; Miller, K. L.; Spenner, K.; Novak, V.; Michelson, P. F.; Whitten, R. C.

    1980-01-01

    The suprathermal electron energy distribution for the dayside ionosphere has been derived from data returned by the Pioneer-Venus orbiter retarding potential analyzer. The shape and magnitude of the spectrum are consistent with the assumption that solar EUV radiation is the only significant source. The magnitude of the spectrum and its variation with altitude suggest that significant vertical transport occurs, with the electrons being lost through the ionopause. In turn, significant vertical transport suggests that the effective vertical electron heat conductivity may be comparable to the field-free value. The heat input to the thermal electron gas from the measured suprathermal electron flux is too small by a factor of at least five to maintain the observed electron temperature profile if the electron thermal conductivity is assumed to be close to the field-free value. It is thus inferred that most of the heat is supplied by the solar wind.

  20. Measurement of Strain and Stress Distributions in Structural Materials by Electron Moiré Method

    NASA Astrophysics Data System (ADS)

    Kishimoto, Satoshi; Xing, Yougming; Tanaka, Yoshihisa; Kagawa, Yutaka

    A method for measuring the strain and stress distributions in structural materials has been introduced. Fine model grids were fabricated by electron beam lithography, and an electron beam scan by a scanning electron microscope (SEM) was used as the master grid. Exposure of the electron beam scan onto the model grid in an SEM produced the electron beam moiré fringes of bright and dark parts caused by the different amounts of the secondary electrons per a primary electron. For demonstration, the micro-creep deformation of pure copper was observed. The creep strain distribution and the grain boundary sliding were analyzed. The residual strain and stress at the interface between a fiber and a matrix of a fiber reinforced plastic (FRP) were measured using the pushing-out test and this electron moiré method. Also, a non-uniform deformation around the boundary of 3-point bended laminated steel was observed and the strain distribution analyzed.

  1. Oncoprotein p28 GANK binds to RelA and retains NF-kappaB in the cytoplasm through nuclear export.

    PubMed

    Chen, Yao; Li, Hong Hai; Fu, Jing; Wang, Xue Feng; Ren, Yi Bin; Dong, Li Wei; Tang, Shan Hua; Liu, Shu Qing; Wu, Meng Chao; Wang, Hong Yang

    2007-12-01

    p28(GANK) (also known as PSMD10, p28 and gankyrin) is an ankyrin repeat anti-apoptotic oncoprotein that is commonly overexpressed in hepatocellular carcinomas and increases the degradation of p53 and Rb. NF-kappaB (nuclear factor-kappaB) is known to be sequestered in the cytoplasm by I kappaB (inhibitor of NF-kappaB) proteins, but much less is known about the cytoplasmic retention of NF-kappaB by other cellular proteins. Here we show that p28(GANK) inhibits NF-kappaB activity. As a nuclear-cytoplasmic shuttling protein, p28(GANK) directly binds to NF-kappaB/RelA and exports RelA from nucleus through a chromosomal region maintenance-1 (CRM-1) dependent pathway, which results in the cytoplasmic retention of NF-kappaB/RelA. We demonstrate that all the ankyrin repeats of p28(GANK) are required for the interaction with RelA and that the N terminus of p28(GANK), which contains the nuclear export sequence (NES), is responsible for suppressing NF-kappaB/RelA nuclear translocation. These results suggest that overexpression of p28(GANK) prevents the nuclear localization and inhibits the activity of NF-kappaB/RelA.

  2. Inter-Coder Agreement in One-to-Many Classification: Fuzzy Kappa.

    PubMed

    Kirilenko, Andrei P; Stepchenkova, Svetlana

    2016-01-01

    Content analysis involves classification of textual, visual, or audio data. The inter-coder agreement is estimated by making two or more coders to classify the same data units, with subsequent comparison of their results. The existing methods of agreement estimation, e.g., Cohen's kappa, require that coders place each unit of content into one and only one category (one-to-one coding) from the pre-established set of categories. However, in certain data domains (e.g., maps, photographs, databases of texts and images), this requirement seems overly restrictive. The restriction could be lifted, provided that there is a measure to calculate the inter-coder agreement in the one-to-many protocol. Building on the existing approaches to one-to-many coding in geography and biomedicine, such measure, fuzzy kappa, which is an extension of Cohen's kappa, is proposed. It is argued that the measure is especially compatible with data from certain domains, when holistic reasoning of human coders is utilized in order to describe the data and access the meaning of communication.

  3. Inter-Coder Agreement in One-to-Many Classification: Fuzzy Kappa

    PubMed Central

    Kirilenko, Andrei P.; Stepchenkova, Svetlana

    2016-01-01

    Content analysis involves classification of textual, visual, or audio data. The inter-coder agreement is estimated by making two or more coders to classify the same data units, with subsequent comparison of their results. The existing methods of agreement estimation, e.g., Cohen’s kappa, require that coders place each unit of content into one and only one category (one-to-one coding) from the pre-established set of categories. However, in certain data domains (e.g., maps, photographs, databases of texts and images), this requirement seems overly restrictive. The restriction could be lifted, provided that there is a measure to calculate the inter-coder agreement in the one-to-many protocol. Building on the existing approaches to one-to-many coding in geography and biomedicine, such measure, fuzzy kappa, which is an extension of Cohen’s kappa, is proposed. It is argued that the measure is especially compatible with data from certain domains, when holistic reasoning of human coders is utilized in order to describe the data and access the meaning of communication. PMID:26933956

  4. Analysis and Quantitation of NF-[kappa]B Nuclear Translocation in Tumor Necrosis Factor Alpha (TNF-[alpha]) Activated Vascular Endothelial Cells

    NASA Astrophysics Data System (ADS)

    Fuseler, John W.; Merrill, Dana M.; Rogers, Jennifer A.; Grisham, Matthew B.; Wolf, Robert E.

    2006-07-01

    Nuclear factor kappa B (NF-[kappa]B) is a heterodimeric transcription factor typically composed of p50 and p65 subunits and is a pleiotropic regulator of various inflammatory and immune responses. In quiescent cells, p50/p65 dimers are sequestered in the cytoplasm bound to its inhibitors, the I-[kappa]Bs, which prevent entry into the nucleus. Following cellular stimulation, the I-[kappa]Bs are rapidly degraded, activating NF-[kappa]B. The active form of NF-[kappa]B rapidly translocates into the nucleus, binding to consensus sequences in the promoter/enhancer region of various genes, promoting their transcription. In human vascular endothelial cells activated with tumor necrosis factor-alpha, the activation and translocation of NF-[kappa]B is rapid, reaching maximal nuclear localization by 30 min. In this study, the appearance of NF-[kappa]B (p65 subunit, p65-NF-[kappa]B) in the nucleus visualized by immunofluorescence and quantified by morphometric image analysis (integrated optical density, IOD) is compared to the appearance of activated p65-NF-[kappa]B protein in the nucleus determined biochemically. The appearance of p65-NF-[kappa]B in the nucleus measured by fluorescence image analysis and biochemically express a linear correlation (R2 = 0.9477). These data suggest that localization and relative protein concentrations of NF-[kappa]B can be reliably determined from IOD measurements of the immunofluorescent labeled protein.

  5. Electroacoustic theory for concentrated colloids with overlapped DLs at arbitrary kappa alpha. I. Application to nanocolloids and nonaqueous colloids.

    PubMed

    Shilov, V N; Borkovskaja, Y B; Dukhin, A S

    2004-09-15

    Existing theories of electroacoustic phenomena in concentrated colloids neglect the possibility of double layer overlap and are valid mostly for the "thin double layer," when the double layer thickness is much less than the particle size. In this paper we present a new electroacoustic theory which removes this restriction. This would make this new theory applicable to characterizing a variety of aqueous nanocolloids and of nonaqueous dispersions. There are two versions of the theory leading to the analytical solutions. The first version corresponds to strongly overlapped diffuse layers (so-called quasi-homogeneous model). It yields a simple analytical formula for colloid vibration current (CVI), which is valid for arbitrary ultrasound frequency, but for restricted kappa alpha range. This version of the theory, as well the Smoluchowski theory for microelectrophoresis, is independent of particle shape and polydispersity. This makes it very attractive for practical use, with the hope that it might be as useful as classical Smoluchowski theory. In order to determine the kappa alpha range of the quasi-homogeneous model validity we develop the second version that limits ultrasound frequency, but applies no restriction on kappa alpha. The ultrasound frequency should substantially exceed the Maxwell-Wagner relaxation frequency. This limitation makes active conductivity related current negligible compared to the passive dielectric displacement current. It is possible to derive an expression for CVI in the concentrated dispersion as formulae inhering definite integrals with integrands depending on equilibrium potential distribution. This second version allowed us to estimate the ranges of the applicability of the first, quasi-homogeneous version. It turns out that the quasi-homogeneous model works for kappa alpha values up to almost 1. For instance, at volume fraction 30%, the highest kappa alpha limit of the quasi-homogeneous model is 0.65. Therefore, this version of the

  6. IgA-kappa type multiple myeloma affecting proximal and distal renal tubules.

    PubMed

    Minemura, K; Ichikawa, K; Itoh, N; Suzuki, N; Hara, M; Shigematsu, S; Kobayashi, H; Hiramatsu, K; Hashizume, K

    2001-09-01

    A 45-year-old male was admitted because of chest pain, lumbago, and bilateral ankle pain. Examination disclosed hypophosphatemic osteomalacia, acquired Fanconi syndrome, and abnormalities in distal nephron such as distal renal tubular acidosis and renal diabetes insipidus. Further exploration revealed IgA kappa multiple myeloma excreting urinary Bence Jones protein (kappa-light chain). Renal biopsy revealed thick basement membranes and elec-tron-dense crystals in proximal tubular epithelial cells. Immunofluorescent studies revealed deposition of kappa-light chain in renal tubular epithelial cells that caused the renal tubular damage. Although the osteomalacia was relieved by medical treatment, the urinary Bence Jones protein and the renal tubular defects were not improved by the chemotherapy for the myeloma. The patient died of exacerbation of multiple myeloma at 50 years of age.

  7. 77 FR 5470 - Periodicals-Recognition of Distribution of Periodicals via Electronic Copies

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-03

    ... Electronic Copies AGENCY: Postal Service TM . ACTION: Proposed rule. SUMMARY: The Postal Service proposes to....6, to allow publishers who use electronic distribution methods to report such circulation as paid or... publications through various electronic media channels. According to the standards that govern the Periodicals...

  8. Oblique ion-acoustic cnoidal waves in two temperature superthermal electrons magnetized plasma

    NASA Astrophysics Data System (ADS)

    Panwar, A.; Ryu, C. M.; Bains, A. S.

    2014-12-01

    A study is presented for the oblique propagation of ion acoustic cnoidal waves in a magnetized plasma consisting of cold ions and two temperature superthermal electrons modelled by kappa-type distributions. Using the reductive perturbation method, the nonlinear Korteweg de-Vries equation is derived, which further gives the solutions with a special type of cnoidal elliptical functions. Both compressive and rarefactive structures are found for these cnoidal waves. Nonlinear periodic cnoidal waves are explained in terms of plasma parameters depicting the Sagdeev potential and the phase curves. It is found that the density ratio of hot electrons to ions μ significantly modifies compressive/refractive wave structures. Furthermore, the combined effects of superthermality of cold and hot electrons κ c , κ h , cold to hot electron temperature ratio σ, angle of propagation and ion cyclotron frequency ωci have been studied in detail to analyze the height and width of compressive/refractive cnoidal waves. The findings in the present study could have important implications in understanding the physics of electrostatic wave structures in the Saturn's magnetosphere where two temperature superthermal electrons are present.

  9. Reciprocal inhibition of p53 and nuclear factor-kappaB transcriptional activities determines cell survival or death in neurons.

    PubMed

    Culmsee, Carsten; Siewe, Jan; Junker, Vera; Retiounskaia, Marina; Schwarz, Stephanie; Camandola, Simonetta; El-Metainy, Shahira; Behnke, Hagen; Mattson, Mark P; Krieglstein, Josef

    2003-09-17

    The tumor suppressor and transcription factor p53 is a key modulator of cellular stress responses, and activation of p53 precedes apoptosis in many cell types. Controversial reports exist on the role of the transcription factor nuclear factor-kappaB (NF-kappaB) in p53-mediated apoptosis, depending on the cell type and experimental conditions. Therefore, we sought to elucidate the role of NF-kappaB in p53-mediated neuron death. In cultured neurons DNA damaging compounds induced activation of p53, whereas NF-kappaB activity declined significantly. The p53 inhibitor pifithrin-alpha (PFT) preserved NF-kappaB activity and protected neurons against apoptosis. Immunoprecipitation experiments revealed enhanced p53 binding to the transcriptional cofactor p300 after induction of DNA damage, whereas binding of p300 to NF-kappaB was reduced. In contrast, PFT blocked the interaction of p53 with the cofactor, whereas NF-kappaB binding to p300 was enhanced. Most interestingly, similar results were observed after oxygen glucose deprivation in cultured neurons and in ischemic brain tissue. Ischemia-induced repression of NF-kappaB activity was prevented and brain damage was reduced by the p53 inhibitor PFT in a dose-dependent manner. It is concluded that a balanced competitive interaction of p53 and NF-kappaB with the transcriptional cofactor p300 exists in neurons. Exposure of neurons to lethal stress activates p53 and disrupts NF-kappaB binding to p300, thereby blocking NF-kappaB-mediated survival signaling. Inhibitors of p53 provide pronounced neuroprotective effects because they block p53-mediated induction of cell death and concomitantly enhance NF-kappaB-induced survival signaling.

  10. Properties of pellets manufactured by wet extrusion/spheronization process using kappa-carrageenan: effect of process parameters.

    PubMed

    Thommes, Markus; Kleinebudde, Peter

    2007-11-09

    The aim of this study was to systematically evaluate the pelletization process parameters of kappa-carrageenan-containing formulations. The study dealt with the effect of 4 process parameters--screw speed, number of die holes, friction plate speed, and spheronizer temperature--on the pellet properties of shape, size, size distribution, tensile strength, and drug release. These parameters were varied systematically in a 2(4) full factorial design. In addition, 4 drugs--phenacetin, chloramphenicol, dimenhydrinate, and lidocaine hydrochloride--were investigated under constant process conditions. The most spherical pellets were achieved in a high yield by using a large number of die holes and a high spheronizer speed. There was no relevant influence of the investigated process parameters on the size distribution, mechanical stability, and drug release. The poorly soluble drugs, phenacetin and chloramphenicol, resulted in pellets with adequate shape, size, and tensile strength and a fast drug release. The salts of dimenhydrinate and lidocaine affected pellet shape, mechanical stability, and the drug release properties using an aqueous solution of pH 3 as a granulation liquid. In the case of dimenhydrinate, this was attributed to the ionic interactions with kappa-carrageenan, resulting in a stable matrix during dissolution that did not disintegrate. The effect of lidocaine is comparable to the effect of sodium ions, which suppress the gelling of carrageenan, resulting in pellets with fast disintegration and drug release characteristics. The pellet properties are affected by the process parameters and the active pharmaceutical ingredient used.

  11. Induction of oncogene addiction shift to NF-{kappa}B by camptothecin in solid tumor cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Togano, Tomiteru; Sasaki, Masataka; Watanabe, Mariko

    2009-12-04

    The biological basis of the resistance of solid tumor cells to chemotherapy is not well understood. While addressing this problem, we found that gastric cancer cell line St-4/CPT, lung cancer cell line A549/CPT, and colon cancer cell line HT-29/CPT, all of which are resistant to camptothecin (CPT), showed strong and constitutive nuclear factor (NF)-{kappa}B activity driven by I{kappa}B kinase compared with their parental cell lines St-4, A549, and HT-29. A new NF-{kappa}B inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), reduced viability and induced apoptosis in St-4/CPT, A549/CPT, and HT-29/CPT cell lines, while their parental cell lines were resistant to DHMEQ. The results in thismore » study present an example of the shift in signals that support the survival of solid tumor cells to NF-{kappa}B during the acquisition of resistance to CPT. The results also indicate that solid tumor cells that become resistant to chemotherapy may be more easily treated by NF-{kappa}B inhibitors.« less

  12. NMR study on the network structure of a mixed gel of kappa and iota carrageenans.

    PubMed

    Hu, Bingjie; Du, Lei; Matsukawa, Shingo

    2016-10-05

    The temperature dependencies of the (1)H T2 and diffusion coefficient (D) of a mixed solution of kappa-carrageenan and iota-carrageenan were measured by NMR. Rheological and NMR measurements suggested an exponential formation of rigid aggregates of kappa-carrageenan and a gradual formation of fine aggregates of iota-carrageenan during two step increases of G'. The results also suggested that longer carrageenan chains are preferentially involved in aggregation, thus resulting in a decrease in the average Mw of solute carrageenans. The results of diffusion measurements for poly(ethylene oxide) (PEO) suggested that kappa-carrageenan formed thick aggregates that decreased hindrance to PEO diffusion by decreasing the solute kappa-carrageenan concentration in the voids of the aggregated chains, and that iota-carrageenan formed fine aggregates that decreased the solute iota-carrageenan concentration less. DPEO in a mixed solution of kappa-carrageenan and iota-carrageenan suggested two possibilities for the microscopic network structure: an interpenetrating network structure, or micro-phase separation. Copyright © 2016. Published by Elsevier Ltd.

  13. 77 FR 27125 - Periodicals-Recognition of Distribution of Periodicals via Electronic Copies

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-09

    ... Electronic Copies AGENCY: Postal Service\\TM\\. ACTION: Final rule. SUMMARY: The Postal Service will revise the... limited reporting of electronic copies of Periodicals publications to satisfy the circulation standards...--Recognition of Distribution of Periodicals via Electronic Copies (77 FR 5470-5471) revising DMM 707.6 by...

  14. Identification of known drugs that act as inhibitors of NF-kappaB signaling and their mechanism of action.

    PubMed

    Miller, Susanne C; Huang, Ruili; Sakamuru, Srilatha; Shukla, Sunita J; Attene-Ramos, Matias S; Shinn, Paul; Van Leer, Danielle; Leister, William; Austin, Christopher P; Xia, Menghang

    2010-05-01

    Nuclear factor-kappa B (NF-kappaB) is a transcription factor that plays a critical role across many cellular processes including embryonic and neuronal development, cell proliferation, apoptosis, and immune responses to infection and inflammation. Dysregulation of NF-kappaB signaling is associated with inflammatory diseases and certain cancers. Constitutive activation of NF-kappaB signaling has been found in some types of tumors including breast, colon, prostate, skin and lymphoid, hence therapeutic blockade of NF-kappaB signaling in cancer cells provides an attractive strategy for the development of anticancer drugs. To identify small molecule inhibitors of NF-kappaB signaling, we screened approximately 2800 clinically approved drugs and bioactive compounds from the NIH Chemical Genomics Center Pharmaceutical Collection (NPC) in a NF-kappaB mediated beta-lactamase reporter gene assay. Each compound was tested at fifteen different concentrations in a quantitative high throughput screening format. We identified nineteen drugs that inhibited NF-kappaB signaling, with potencies as low as 20 nM. Many of these drugs, including emetine, fluorosalan, sunitinib malate, bithionol, narasin, tribromsalan, and lestaurtinib, inhibited NF-kappaB signaling via inhibition of IkappaBalpha phosphorylation. Others, such as ectinascidin 743, chromomycin A3 and bortezomib utilized other mechanisms. Furthermore, many of these drugs induced caspase 3/7 activity and had an inhibitory effect on cervical cancer cell growth. Our results indicate that many currently approved pharmaceuticals have previously unappreciated effects on NF-kappaB signaling, which may contribute to anticancer therapeutic effects. Comprehensive profiling of approved drugs provides insight into their molecular mechanisms, thus providing a basis for drug repurposing. Published by Elsevier Inc.

  15. NIK and IKKbeta interdependence in NF-kappaB signalling--flux analysis of regulation through metabolites.

    PubMed

    Kim, Hong-Bum; Evans, Iona; Smallwood, Rod; Holcombe, Mike; Qwarnstrom, Eva E

    2010-02-01

    Activation of the transcription factor NF-kappaB is central to control of immune and inflammatory responses. Cytokine induced activation through the classical or canonical pathway relies on degradation of the inhibitor, IkappaBalpha and regulation by the IKKbeta kinase. In addition, the NF-kappaB is activated through the NF-kappaB-inducing kinase, NIK. Analysis of the IKK/NIK inter-relationship and its impact on NF-kappaB control, were analysed by mathematical modelling, using matrix formalism and stoichiometrically balanced reactions. The analysis considered a range of bio-reactions and core metabolites and their role in relation to kinase activation and in control of specific steps of the NF-kappaB pathway. The model predicts a growth-rate and time-dependent transfer of the primary kinase activity from IKKbeta to NIK. In addition, it suggests that NIK/IKKbeta interdependence is controlled by intermediates of phosphoribosylpyrophosphate (PRPP) within the glycolysis pathway, and thus, identifies a link between specific metabolic events and kinase activation in inflammatory signal transduction. Subsequent in vitro experiments, carried out to validate the impact of IKK/NIK interdependence, confirmed signal amplification at the level of the NF-kappaB/IkappaBalpha complex control in the presence of both kinases. Further, they demonstrate that the induced potentiation is due to synergistic enhancement of relA-dependent activation. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

  16. Rapid flattening of butterfly pitch angle distributions of radiation belt electrons by whistler-mode chorus

    NASA Astrophysics Data System (ADS)

    Yang, Chang; Su, Zhenpeng; Xiao, Fuliang; Zheng, Huinan; Wang, Yuming; Wang, Shui; Spence, H. E.; Reeves, G. D.; Baker, D. N.; Blake, J. B.; Funsten, H. O.

    2016-08-01

    Van Allen radiation belt electrons exhibit complex dynamics during geomagnetically active periods. Investigation of electron pitch angle distributions (PADs) can provide important information on the dominant physical mechanisms controlling radiation belt behaviors. Here we report a storm time radiation belt event where energetic electron PADs changed from butterfly distributions to normal or flattop distributions within several hours. Van Allen Probes observations showed that the flattening of butterfly PADs was closely related to the occurrence of whistler-mode chorus waves. Two-dimensional quasi-linear STEERB simulations demonstrate that the observed chorus can resonantly accelerate the near-equatorially trapped electrons and rapidly flatten the corresponding electron butterfly PADs. These results provide a new insight on how chorus waves affect the dynamic evolution of radiation belt electrons.

  17. Curcumin Regulates Low-Linear Energy Transfer {gamma}-Radiation-Induced NF{kappa}B-Dependent Telomerase Activity in Human Neuroblastoma Cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Aravindan, Natarajan, E-mail: naravind@ouhsc.ed; Veeraraghavan, Jamunarani; Madhusoodhanan, Rakhesh

    2011-03-15

    Purpose: We recently reported that curcumin attenuates ionizing radiation (IR)-induced survival signaling and proliferation in human neuroblastoma cells. Also, in the endothelial system, we have demonstrated that NF{kappa}B regulates IR-induced telomerase activity (TA). Accordingly, we investigated the effect of curcumin in inhibiting IR-induced NF{kappa}B-dependent hTERT transcription, TA, and cell survival in neuroblastoma cells. Methods and Materials: SK-N-MC or SH-SY5Y cells exposed to IR and treated with curcumin (10-100 nM) with or without IR were harvested after 1 h through 24 h. NF{kappa}B-dependent regulation was investigated either by luciferase reporter assays using pNF{kappa}B-, pGL3-354-, pGL3-347-, or pUSE-I{kappa}B{alpha}-Luc, p50/p65, or RelA siRNA-transfectedmore » cells. NF{kappa}B activity was analyzed using an electrophoretic mobility shift assay and hTERT expression using the quantitative polymerase chain reaction. TA was determined using the telomerase repeat amplification protocol assay and cell survival using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltertrazolium bromide and clonogenic assay. Results: Curcumin profoundly inhibited IR-induced NF{kappa}B. Consequently, curcumin significantly inhibited IR-induced TA and hTERT mRNA at all points investigated. Furthermore, IR-induced TA is regulated at the transcriptional level by triggering telomerase reverse transcriptase (TERT) promoter activation. Moreover, NF{kappa}B becomes functionally activated after IR and mediates TA upregulation by binding to the {kappa}B-binding region in the promoter region of the TERT gene. Consistently, elimination of the NF{kappa}B-recognition site on the telomerase promoter or inhibition of NF{kappa}B by the I{kappa}B{alpha} mutant compromises IR-induced telomerase promoter activation. Significantly, curcumin inhibited IR-induced TERT transcription. Consequently, curcumin inhibited hTERT mRNA and TA in NF{kappa}B overexpressed cells. Furthermore, curcumin

  18. Experimental investigations into visual and electronic tooth color measurement.

    PubMed

    Ratzmann, Anja; Treichel, Anja; Langforth, Gabriele; Gedrange, Tomasz; Welk, Alexander

    2011-04-01

    The present study aimed to examine the validity of the visual color assessment and an electronic tooth color measurement system by means of Shade Inspector™ in comparison with a gold standard. Additionally, reproducibility of electronic measurements was demonstrated by means of two reference systems. Ceramic specimens of two thicknesses (h=1.6 mm, h=2.6 mm) were used. Three experienced dental technicians using the VITAPAN Classical(®) color scale carried out all visual tests. Validity of the visual assessment and the electronic measurements was confirmed separately for both thicknesses by means of lightness and hue of the VITAPAN Classical(®) color scale. Reproducibility of electronic measurements was confirmed by means of the VITAPAN Classical(®) and 3D-Master(®). The 3D-Master(®) data were calculated according to lightness, hue and chroma. Intraclass correlation coefficient (ICC) was used in assessing validity/reproducibility for lightness and chroma, Kappa statistics were used for hue. A level ≥0.75 was pre-established for ICC and ≥0.60 for the Kappa index. RESULTS OF VISUAL COLOR ASSESSMENT: Validity for lightness was good for both thicknesses; agreement rates for hue were inconsistent. ELECTRONIC MEASUREMENT: Validity for lightness was fair to good, hue values were below 0.60. Reproducibility of lightness was good to very good for both reference systems. Hue values (VITAPAN Classical(®)) for 1.6 mm test specimens were upside, for 2.6 mm below 0.60, Kappa values for 3D-Master(®) were ≥0.60 for all measurements, reproducibility of chroma was very good. Validity was better for visual than for electronic color assessment. Reproducibility of the electronic device by means of the Shade Inspector™ was given for the VITAPAN Classical(®) and 3D-Master(®) systems.

  19. Supersensitive Kappa Opioid Receptors Promotes Ethanol Withdrawal-Related Behaviors and Reduce Dopamine Signaling in the Nucleus Accumbens.

    PubMed

    Rose, Jamie H; Karkhanis, Anushree N; Chen, Rong; Gioia, Dominic; Lopez, Marcelo F; Becker, Howard C; McCool, Brian A; Jones, Sara R

    2016-05-01

    Chronic ethanol exposure reduces dopamine transmission in the nucleus accumbens, which may contribute to the negative affective symptoms associated with ethanol withdrawal. Kappa opioid receptors have been implicated in withdrawal-induced excessive drinking and anxiety-like behaviors and are known to inhibit dopamine release in the nucleus accumbens. The effects of chronic ethanol exposure on kappa opioid receptor-mediated changes in dopamine transmission at the level of the dopamine terminal and withdrawal-related behaviors were examined. Five weeks of chronic intermittent ethanol exposure in male C57BL/6 mice were used to examine the role of kappa opioid receptors in chronic ethanol-induced increases in ethanol intake and marble burying, a measure of anxiety/compulsive-like behavior. Drinking and marble burying were evaluated before and after chronic intermittent ethanol exposure, with and without kappa opioid receptor blockade by nor-binaltorphimine (10mg/kg i.p.). Functional alterations in kappa opioid receptors were assessed using fast scan cyclic voltammetry in brain slices containing the nucleus accumbens. Chronic intermittent ethanol-exposed mice showed increased ethanol drinking and marble burying compared with controls, which was attenuated with kappa opioid receptor blockade. Chronic intermittent ethanol-induced increases in behavior were replicated with kappa opioid receptor activation in naïve mice. Fast scan cyclic voltammetry revealed that chronic intermittent ethanol reduced accumbal dopamine release and increased uptake rates, promoting a hypodopaminergic state of this region. Kappa opioid receptor activation with U50,488H concentration-dependently decreased dopamine release in both groups; however, this effect was greater in chronic intermittent ethanol-treated mice, indicating kappa opioid receptor supersensitivity in this group. These data suggest that the chronic intermittent ethanol-induced increase in ethanol intake and anxiety

  20. Analytic non-Maxwellian electron velocity distribution function in a Hall discharge plasma

    NASA Astrophysics Data System (ADS)

    Shagayda, Andrey; Tarasov, Alexey

    2017-10-01

    The electron velocity distribution function in the low-pressure discharges with the crossed electric and magnetic fields, which occur in magnetrons, plasma accelerators, and Hall thrusters with a closed electron drift, is not Maxwellian. A deviation from equilibrium is caused by a large electron mean free path relative to the Larmor radius and the size of the discharge channel. In this study, we derived in the relaxation approximation the analytical expression of the electron velocity distribution function in a weakly ionized Lorentz plasma with the crossed electric and magnetic fields in the presence of the electron density and temperature gradients in the direction of the electric field. The solution was obtained in the stationary approximation far from boundary surfaces, when diffusion and mobility are determined by the classical effective collision frequency of electrons with ions and atoms. The moments of the distribution function including the average velocity, the stress tensor, and the heat flux were calculated and compared with the classical hydrodynamic expressions. It was shown that a kinetic correction to the drift velocity stems from a contribution of the off-diagonal component of the stress tensor. This correction becomes essential if the drift velocity in the crossed electric and magnetic fields would be comparable to the thermal velocity of electrons. The electron temperature has three different components at a nonzero effective collision frequency and two different components in the limit when the collision frequency tends to zero. It is shown that, in the presence of ionization collisions, the components of the heat flux have additives that are not related to the temperature gradient, and arise because of the electron drift.

  1. Over-expression of Flt3 induces NF-kappaB pathway and increases the expression of IL-6.

    PubMed

    Takahashi, Shinichiro; Harigae, Hideo; Ishii, Keiko Kumura; Inomata, Mitsue; Fujiwara, Tohru; Yokoyama, Hisayuki; Ishizawa, Kenichi; Kameoka, Junichi; Licht, Jonathan D; Sasaki, Takeshi; Kaku, Mitsuo

    2005-08-01

    Activating mutations or over-expression of the Flt3 is prevalent in acute myeloblastic leukemia (AML), associated with activation of Ras/MAP kinase and other signaling pathways. In this study, we addressed the role of Flt3 in the activation of nuclear factor-kappa B (NF-kappaB), which is a target molecule of these kinase pathways. In BaF3 cells stably expressing Flt3, a NF-kappaB-responsive reporter was upregulated and its target gene, IL-6, was increased by the involvement of Flt3-ERK/MAPK-NF-kappaB pathway. Furthermore, we found a modest positive correlation (r=0.35, p=0.096) between Flt3 and IL-6 mRNA expression in 24 AML specimens. These results suggest a role of Flt3 over-expression in NF-kappaB pathway.

  2. Internal Passage Heat Transfer Prediction Using Multiblock Grids and a Kappa-Omega Turbulence Model

    NASA Technical Reports Server (NTRS)

    Rigby, David L.; Ameri, Ali A.; Steinthorsson, Erlendur

    1996-01-01

    Numerical simulations of the three-dimensional flow and heat transfer in a rectangular duct with a 180 C bend were performed. Results are presented for Reynolds numbers of 17,000 and 37,000 and for aspect ratios of 0.5 and I.O. A kappa-omega turbulence model with no reference to distance to a wall is used. Direct comparison between single block and multiblock grid calculations are made. Heat transfer and velocity distributions are compared to available literature with good agreement. The multi-block grid system is seen to produce more accurate results compared to a single-block grid with the same number of cells.

  3. Acid gelation properties of heated skim milk as a result of enzymatically induced changes in the micelle/serum distribution of the whey protein/kappa-casein aggregates.

    PubMed

    Guyomarc'h, Fanny; Renan, Marie; Chatriot, Marc; Gamerre, Valérie; Famelart, Marie-Hélène

    2007-12-26

    Changes in the acid gelation properties of skim milk as a result of variations in the micelle/serum distribution of the heat-induced whey protein/kappa-casein aggregates, induced by the combination of heat treatment and limited renneting, were investigated. No dramatic change in the zeta potential or the isoelectric point of the casein micelles was suggested, whether the aggregates were all attached to the casein micelle or not. Fluorescence intensity measurement using 8-anilino-1-naphthalenesulfonic acid (ANS) showed that the heat-induced aggregates were highly hydrophobic. Dynamic oscillation viscosimetry showed that acid gelation using glucono-delta-lactone (GDL) started at a higher pH value in prerenneted milk. However, no change in the gelation profile of skim milk could be related to the proportion of aggregates bound to the surface of the casein micelles. The results support the idea of an early interaction between the serum aggregates and the casein micelles on acidification.

  4. Angle Kappa Measurements: Normal Values in Healthy Iranian Population Obtained With the Orbscan II

    PubMed Central

    Gharaee, Hamid; Shafiee, Masoud; Hoseini, Rafie; Abrishami, Mojtaba; Abrishami, Yalda; Abrishami, Mostafa

    2014-01-01

    Background: The angle kappa is important in proper centration of corneal ablation in keratorefractive surgery. Orbscan II device is widely used preoperatively in photoablation surgeries and can be used to measure the angle kappa. Objectives: This study aimed to determine the mean angle kappa and its intercepts in healthy young Iranian adults. Patients and Methods: In this cross-sectional study, orthotropic patients (age range, 18-35 years) who were referred to the Khatam Eye Hospital (Mashhad, Iran) were included. Exclusion criteria were as follows: history of any eye deviation or strabismus with or without orthoptic or surgical treatment; any intraocular, corneal, or keratorefractive surgery; contact lens use; any corneal anomaly; any ophthalmic or systemic drug consumption; and hyperopic spherical refraction > + 3.00 diopters (D), spherical refraction > -5.00 D, or cylindrical refraction > 2.00 D. All of the parameters were measured by the same operator through an Orbscan II device. Results: A total of 977 healthy participants who aged 18 to 45 years were included consecutively. The study population consisted of 614 females and 363 males. The average angle kappa was 5.00º ± 1.36º at 240.21º ± 97.17º in males and 4.97º ± 1.30º at 244.22º ± 94.39º in females (P = 0.63). The average horizontal (x-axis) angle kappa was -0.02º ± 0.49º, with a mean of -0.02º ± 0.50º in males and -0.02º ± 0.49º in females (P = 0.93). The average vertical (y-axis) angle kappa was -0.09º ± 0.32º, with a mean of -0.09º ± 0.33º in males and -0.09º ± 0.32º in females (P = 0.74). Conclusions: By using the normal angle kappa determined in this study, pseudodeviations can be identified more precisely in those who might undergo keratorefractive surgery. PMID:25763261

  5. Shikonin derivatives inhibited LPS-induced NOS in RAW 264.7 cells via downregulation of MAPK/NF-kappaB signaling.

    PubMed

    Cheng, Yu Wen; Chang, Ching Yi; Lin, Kou Lung; Hu, Chien Ming; Lin, Cheng Hui; Kang, Jaw Jou

    2008-11-20

    Shikonin/alkannin (SA) derivatives, analogs of naphthoquinone pigments, are the major components of root extracts of the Chinese medicinal herb (Lithospermum erythrorhizon; LE) and widely distributed in several folk medicines. In the present study, the effect and the underline molecular mechanism of shikonin derivatives isolated from root extracts of Lithospermum euchroma on lipopolysaccharide (LPS)-induced inflammatory response were investigated. Effects of five SA derivatives, including SA, acetylshikonin, beta,beta-dimethylacrylshikonin, 5,8-dihydroxy-1.4-naphthoquinone, and 1,4-naphthoquinone on LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production in mouse macrophage RAW264.7 cells were examined. Data suggested that SA derivatives inhibited LPS-induced NO and PGE(2) production, and iNOS protein expression. RT-PCR analysis showed that SA derivatives diminished LPS-induced iNOS mRNA expression. Moreover, the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 in LPS-stimulated RAW 264.7 cells was concentration-dependently suppressed by SA derivatives. SA inhibited NF-kappaB activation by prevention of the degradation of inhibitory factor-kappaB and p65 level in nuclear fractions induced by LPS. Taken together, these results suggest that the anti-inflammatory properties of SA derivatives might result from inhibition of iNOS protein expression through the downregulation of NF-kappaB activation via suppression of phosphorylation of ERK, in LPS-stimulated RAW 264.7 cells.

  6. Rapid flattening of butterfly pitch angle distributions of radiation belt electrons by whistler-mode chorus

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yang, Chang; Su, Zhenpeng; Xiao, Fuliang

    Van Allen radiation belt electrons exhibit complex dynamics during geomagnetically active periods. Investigation of electron pitch angle distributions (PADs) can provide important information on the dominant physical mechanisms controlling radiation belt behaviors. In this paper, we report a storm time radiation belt event where energetic electron PADs changed from butterfly distributions to normal or flattop distributions within several hours. Van Allen Probes observations showed that the flattening of butterfly PADs was closely related to the occurrence of whistler-mode chorus waves. Two-dimensional quasi-linear STEERB simulations demonstrate that the observed chorus can resonantly accelerate the near-equatorially trapped electrons and rapidly flatten themore » corresponding electron butterfly PADs. Finally, these results provide a new insight on how chorus waves affect the dynamic evolution of radiation belt electrons.« less

  7. Rapid flattening of butterfly pitch angle distributions of radiation belt electrons by whistler-mode chorus

    DOE PAGES

    Yang, Chang; Su, Zhenpeng; Xiao, Fuliang; ...

    2016-08-16

    Van Allen radiation belt electrons exhibit complex dynamics during geomagnetically active periods. Investigation of electron pitch angle distributions (PADs) can provide important information on the dominant physical mechanisms controlling radiation belt behaviors. In this paper, we report a storm time radiation belt event where energetic electron PADs changed from butterfly distributions to normal or flattop distributions within several hours. Van Allen Probes observations showed that the flattening of butterfly PADs was closely related to the occurrence of whistler-mode chorus waves. Two-dimensional quasi-linear STEERB simulations demonstrate that the observed chorus can resonantly accelerate the near-equatorially trapped electrons and rapidly flatten themore » corresponding electron butterfly PADs. Finally, these results provide a new insight on how chorus waves affect the dynamic evolution of radiation belt electrons.« less

  8. Energy Distribution of Electrons in Radiation Induced-Helium Plasmas. Ph.D. Thesis

    NASA Technical Reports Server (NTRS)

    Lo, R. H.

    1972-01-01

    Energy distribution of high energy electrons as they slow down and thermalize in a gaseous medium is studied. The energy distribution in the entire energy range from source energies down is studied analytically. A helium medium in which primary electrons are created by the passage of heavy-charged particles from nuclear reactions is emphasized. A radiation-induced plasma is of interest in a variety of applications, such as radiation pumped lasers and gaseous core nuclear reactors.

  9. TAK1 regulates NF-{Kappa}B and AP-1 activation in airway epithelial cells following RSV infection

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dey, Nilay; Liu Tianshuang; Garofalo, Roberto P.

    2011-09-30

    Respiratory syncytial virus (RSV) is the most common cause of epidemic respiratory diseases in infants and young children. RSV infection of airway epithelial cells induces the expression of immune/inflammatory genes through the activation of a subset of transcription factors, including Nuclear Factor-{kappa}B (NF-{kappa}B) and AP-1. In this study, we have investigated the signaling pathway leading to activation of these two transcription factors in response to RSV infection. Our results show that IKK{beta} plays a key role in viral-induced NF-{kappa}B activation, while JNK regulates AP-1-dependent gene transcription, as demonstrated by using kinase inactive proteins and chemical inhibitors of the two kinases.more » Inhibition of TAK1 activation, by overexpression of kinase inactive TAK1 or using cells lacking TAK1 expression, significantly reduced RSV-induced NF-{kappa}B and AP-1 nuclear translocation and DNA-binding activity, as well as NF-{kappa}B-dependent gene expression, identifying TAK1 as an important upstream signaling molecule regulating RSV-induced NF-{kappa}B and AP-1 activation. - Highlights: > IKK{beta} is a major kinase involved in RSV-induced NF-{kappa}B activation. > JNK regulates AP-1-dependent gene transcription in RSV infection. > TAK1 is a critical upstream signaling molecule for both pathways in infected cells.« less

  10. Prevalence of mutations in hepatitis C virus core protein associated with alteration of NF-kappaB activation.

    PubMed

    Mann, Elizabeth A; Stanford, Sandra; Sherman, Kenneth E

    2006-10-01

    The hepatitis C virus (HCV) core protein is a key structural element of the virion but also affects a number of cellular pathways, including nuclear factor kappaB (NF-kappaB) signaling. NF-kappaB is a transcription factor that regulates both anti-apoptotic and pro-inflammatory genes and its activation may contribute to HCV-mediated pathogenesis. Amino acid sequence divergence in core is seen at the genotype level as well as within patient isolates. Recent work has implicated amino acids 9-11 of core in the modulation of NF-kappaB activation. We report that the sequence RKT is highly conserved (93%) at this position across all HCV genotypes, based on sequences collected in the Los Alamos HCV database. Of the 13 types of variants present in the database, the two most prevalent substitutions are RQT and RKP. We further show that core encoding RKP fails to activate NF-kappaB signaling in vitro while NF-kappaB activation by core encoding RQT does not differ from control RKT core. The effect of RKP core is specific to NF-kappaB signaling as activator protein 1 (AP-1) activity is not altered. Further studies are needed to assess potential associations between specific amino acid substitutions at positions 9-11 and liver disease progression and/or response to treatment in individual patients.

  11. Relationship between carbachol hyperstimulation-induced pancreatic intracellular trypsinogen and NF-kappa B activation in rats in vitro.

    PubMed

    Jiang, Chunfang; Zheng, Hai; Liu, Sunan; Fang, Kaifeng

    2008-02-01

    The relationship between intracellular trypsinogen activation and NF-kappa B activation in rat pancreatic acinar cells induced by M3 cholinergic receptor agonist (carbachol) hyperstimulation was studied. Rat pancreatic acinar cells were isolated, cultured and treated with carbachol, the active protease inhibitor (pefabloc) and NF-kappa B inhibitor (PDTC) in vitro. Intracellular trypsin activity was measured by using a fluorogenic substrate. The activity of NF-kappa B was monitored by using electrophoretic mobility shift assay. The results showed that after pretreatment with 2 mmol/L pefabloc, the activities of trypsin and NF-kappa B in pancreatic acinar cells treated with high concentrations of carbachol (10(-3) mol/L) in vitro was significantly decreased as compared with control group (P<0.01). The addition of 10(-2) mol/L PDTC resulted in a significant decrease of NF-kappa B activities in pancreatic acinar cells after treated with high concentrations of carbachol (10(-3) mol/L) in vitro, but the intracellular trypsinogen activity was not obviously inhibited (P>0.05). It was concluded that intracellular trypsinogen activation is likely involved in the regulation of high concentrations of carbachol-induced NF-kappa B activation in pancreatic acinar cells in vitro. NF-kappa B activation is likely not necessary for high concentrations of carbachol-induced trypsinogen activation in pancreatic acinar cells in vitro.

  12. 40 CFR 721.1880 - Borate(1-), tris(acetato-.kappa.O)hydro-, sodium, (T-4)-.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...)hydro-, sodium, (T-4)-. 721.1880 Section 721.1880 Protection of Environment ENVIRONMENTAL PROTECTION... New Uses for Specific Chemical Substances § 721.1880 Borate(1-), tris(acetato-.kappa.O)hydro-, sodium... substance identified as borate(1-), tris(acetato-.kappa.O)hydro-, sodium, (T-4)- (PMN P-00-0922; CAS No...

  13. 40 CFR 721.1880 - Borate(1-), tris(acetato-.kappa.O)hydro-, sodium, (T-4)-.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...)hydro-, sodium, (T-4)-. 721.1880 Section 721.1880 Protection of Environment ENVIRONMENTAL PROTECTION... New Uses for Specific Chemical Substances § 721.1880 Borate(1-), tris(acetato-.kappa.O)hydro-, sodium... substance identified as borate(1-), tris(acetato-.kappa.O)hydro-, sodium, (T-4)- (PMN P-00-0922; CAS No...

  14. Spacecraft Observations and Analytic Theory of Crescent-Shaped Electron Distributions in Asymmetric Magnetic Reconnection

    NASA Astrophysics Data System (ADS)

    Egedal, J.; Le, A.; Daughton, W.; Wetherton, B.; Cassak, P. A.; Chen, L.-J.; Lavraud, B.; Torbert, R. B.; Dorelli, J.; Gershman, D. J.; Avanov, L. A.

    2016-10-01

    Supported by a kinetic simulation, we derive an exclusion energy parameter EX providing a lower kinetic energy bound for an electron to cross from one inflow region to the other during magnetic reconnection. As by a Maxwell demon, only high-energy electrons are permitted to cross the inner reconnection region, setting the electron distribution function observed along the low-density side separatrix during asymmetric reconnection. The analytic model accounts for the two distinct flavors of crescent-shaped electron distributions observed by spacecraft in a thin boundary layer along the low-density separatrix.

  15. Spacecraft Observations and Analytic Theory of Crescent-Shaped Electron Distributions in Asymmetric Magnetic Reconnection

    NASA Technical Reports Server (NTRS)

    Egedal, J.; Le, A.; Daughton, W.; Wetherton, B.; Cassak, P.A.; Chen, L.-J.; Lavraud, B.; Trobert, Roy; Dorelli, J.; Gershman, D. J.; hide

    2016-01-01

    Supported by a kinetic simulation, we derive an exclusion energy parameter EX providing a lower kinetic energy bound for an electron to cross from one inflow region to the other during magnetic reconnection. As by a Maxwell Demon, only high energy electrons are permitted to cross the inner-reconnection region, setting the electron distribution function observed along the low density side separatrix during asymmetric reconnection. The analytic model accounts for the two distinct flavors of crescent-shaped electron distributions observed by spacecraft in a thin boundary layer along the low density separatrix.

  16. Regional differences in mu and kappa opioid receptor G-protein activation in brain in male and female prairie voles.

    PubMed

    Martin, T J; Sexton, T; Kim, S A; Severino, A L; Peters, C M; Young, L J; Childers, S R

    2015-12-17

    Prairie voles are unusual mammals in that, like humans, they are capable of forming socially monogamous pair bonds, display biparental care, and engage in alloparental behaviors. Both mu and kappa opioid receptors are involved in behaviors that either establish and maintain, or result from pair bond formation in these animals. Mu and kappa opioid receptors both utilize inhibitory G-proteins in signal transduction mechanisms, however the efficacy by which these receptor subtypes stimulate G-protein signaling across the prairie vole neuraxis is not known. Utilizing [(35)S]GTPγS autoradiography, we characterized the efficacy of G-protein stimulation in coronal sections throughout male and female prairie vole brains by [D-Ala2,NMe-Phe4,Gly-ol5]-enkephalin (DAMGO) and U50,488H, selective mu and kappa opioid agonists, respectively. DAMGO stimulation was highest in the forebrain, similar to that found with other rodent species. U-50,488H produced greater stimulation in prairie voles than is typically seen in mice and rats, particularly in select forebrain areas. DAMGO produced higher stimulation in the core versus the shell of the nucleus accumbens (NAc) in females, while the distribution of U-50,488H stimulation was the opposite. There were no gender differences for U50,488H stimulation of G-protein activity across the regions examined, while DAMGO stimulation was greater in sections from females compared to those from males for NAc core, entopeduncular nucleus, and hippocampus. These data suggest that the kappa opioid system may be more sensitive to manipulation in prairie voles compared to mice and rats, and that female prairie voles may be more sensitive to mu agonists in select brain regions than males. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. Electron pitch angle distributions throughout the magnetosphere as observed on Ogo 5.

    NASA Technical Reports Server (NTRS)

    West, H. I., Jr.; Buck, R. M.; Walton, J. R.

    1973-01-01

    A survey of the equatorial pitch angle distributions of energetic electrons is provided for all local times out to radial distances of 20 earth radii on the night side of the earth and to the magnetopause on the day side of the earth. In much of the inner magnetosphere and in the outer magnetosphere on the day side of the earth, the normal loss cone distribution prevails. The effects of drift shell splitting - i.e., the appearance of pitch angle distributions with minimums at 90 deg, called butterfly distributions - become apparent in the early afternoon magnetosphere at extended distances, and the distribution is observed in to 5.5 earth radii in the nighttime magnetosphere. Inside about 9 earth radii the pitch angle effects are quite energy-dependent. Beyond about 9 earth radii in the premidnight magnetosphere during quiet times the butterfly distribution is often observed. It is shown that these electrons cannot survive a drift to dawn without being considerably modified. The role of substorm activity in modifying these distributions is identified.

  18. The stimulation of central kappa opioid receptors decreases male sexual behavior and locomotor activity.

    PubMed

    Leyton, M; Stewart, J

    1992-10-23

    Systemic injections of the kappa (kappa) opioid receptor agonist U-50,488H decreased male sexual behavior, locomotor activity, body temperature and bodily grooming, and induced body flattening. The U-50,488H-induced inhibitions of male sexual behavior were prevented by systemic injections of naloxone and by intra-cranial injections of the kappa opioid antagonist nor-binaltorphimine (NBNI). Injections of NBNI to either the ventral tegmental area (VTA) or the nucleus accumbens septi (NAS) increased female-directed behavior, and prevented the U-50,488H-induced decreases in female-directed behavior. Intra-VTA NBNI prevented U-50,488H-induced decreases in the mean number of ejaculations, intra-NAS NBNI prevented U-50,488H-induced increases in copulation latencies. Intra-medial preoptic area (mPOA) injections of NBNI increased female-directed behavior, and attenuated U-50,488H-induced decreases in female-directed behavior as well as U-50,488H-induced increases in both copulation and ejaculation latencies. Injections of NBNI dorsal to the mPOA were ineffective. Two of 26 days following the central injection of NBNI, systemic injections of U-50,488H remained behaviorally ineffective, leaving both sexual behavior and locomotor activity undiminished. These results suggest that the stimulation of central kappa opioid receptors inhibits sexual behavior in the male rat; perhaps endogenous kappa opioid agonists induce sexual refractory periods.

  19. Omentin inhibits TNF-{alpha}-induced expression of adhesion molecules in endothelial cells via ERK/NF-{kappa}B pathway

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhong, Xia, E-mail: zhongxia1977@126.com; Li, Xiaonan; Liu, Fuli

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Omentin inhibited TNF-{alpha}-induced adhesion of THP-1 cells to HUVECs. Black-Right-Pointing-Pointer Omentin reduces expression of ICAM-1 and VCAM-1 induced by TNF-{alpha} in HUVECs. Black-Right-Pointing-Pointer Omentin inhibits TNF-{alpha}-induced ERK and NF-{kappa}B activation in HUVECs. Black-Right-Pointing-Pointer Omentin supreeses TNF-{alpha}-induced expression of ICAM-1 and VCAM-1 via ERK/NF-{kappa}B pathway. -- Abstract: In the present study, we investigated whether omentin affected the expression of intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in tumor necrosis factor-{alpha} (TNF-{alpha}) induced human umbilical vein endothelial cells (HUVECs). Our data showed that omentin decreased TNF-{alpha}-induced expression of ICAM-1 and VCAM-1 in HUVECs. In addition, omentin inhibitedmore » TNF-{alpha}-induced adhesion of THP-1 cells to HUVECs. Further, we found that omentin inhibited TNF-{alpha}-activated signal pathway of nuclear factor-{kappa}B (NF-{kappa}B) by preventing NF-{kappa}B inhibitory protein (I{kappa}B{alpha}) degradation and NF-{kappa}B/DNA binding activity. Omentin pretreatment significantly inhibited TNF-{alpha}-induced ERK activity and ERK phosphorylation in HUVECs. Pretreatment with PD98059 suppressed TNF-{alpha}-induced NF-{kappa}B activity. Omentin, NF-kB inhibitor (BAY11-7082) and ERK inhibitor (PD98059) reduced the up-regulation of ICAM-1 and VCAM-1 induced by TNF-{alpha}. These results suggest that omentin may inhibit TNF-{alpha}-induced expression of adhesion molecules in endothelial cells via blocking ERK/NF-{kappa}B pathway.« less

  20. Are anesthesia start and end times randomly distributed? The influence of electronic records.

    PubMed

    Deal, Litisha G; Nyland, Michael E; Gravenstein, Nikolaus; Tighe, Patrick

    2014-06-01

    To perform a frequency analysis of start minute digits (SMD) and end minute digits (EMD) taken from the electronic, computer-assisted, and manual anesthesia billing-record systems. Retrospective cross-sectional review. University medical center. This cross-sectional review was conducted on billing records from a single healthcare institution over a 15-month period. A total of 30,738 cases were analyzed. For each record, the start time and end time were recorded. Distributions of SMD and EMD were tested against the null hypothesis of a frequency distribution equivalently spread between zero and nine. SMD and EMD aggregate distributions each differed from equivalency (P < 0.0001). When stratified by type of anesthetic record, no differences were found between the recorded and expected equivalent distribution patterns for electronic anesthesia records for start minute (P < 0.98) or end minute (P < 0.55). Manual and computer-assisted records maintained nonequivalent distribution patterns for SMD and EMD (P < 0.0001 for each comparison). Comparison of cumulative distributions between SMD and EMD distributions suggested a significant difference between the two patterns (P < 0.0001). An electronic anesthesia record system, with automated time capture of events verified by the user, produces a more unified distribution of billing times than do more traditional methods of entering billing times. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Curcumin Modulates the Radiosensitivity of Colorectal Cancer Cells by Suppressing Constitutive and Inducible NF-{kappa}B Activity

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sandur, Santosh K.; Deorukhkar, Amit; Pandey, Manoj K.

    2009-10-01

    Purpose: Radiation therapy is an integral part of the preoperative treatment of rectal cancers. However, only a minority of patients achieve a complete pathologic response to therapy because of resistance of these tumors to radiation therapy. This resistance may be mediated by constitutively active pro-survival signaling pathways or by inducible/acquired mechanisms in response to radiation therapy. Simultaneous inhibition of these pathways can sensitize these tumors to radiation therapy. Methods and Materials: Human colorectal cancer cells were exposed to clinically relevant doses of gamma rays, and the mechanism of their radioresistance was investigated. We characterized the transcription factor nuclear factor-{kappa}B (NF-{kappa}B)more » activation as a mechanism of inducible radioresistance in colorectal cancer and used curcumin, the active ingredient in the yellow spice turmeric, to overcome this resistance. Results: Curcumin inhibited the proliferation and the post-irradiation clonogenic survival of multiple colorectal cancer cell lines. Radiation stimulated NF-{kappa}B activity in a dose- and time-dependent manner, whereas curcumin suppressed this radiation-induced NF-{kappa}B activation via inhibition of radiation-induced phosphorylation and degradation of inhibitor of {kappa}B alpha, inhibition of inhibitor of {kappa}B kinase activity, and inhibition of Akt phosphorylation. Curcumin also suppressed NF-{kappa}B-regulated gene products (Bcl-2, Bcl-x{sub L}, inhibitor of apoptosis protein-2, cyclooxygenase-2, and cyclin D1). Conclusions: Our results suggest that transient inducible NF-{kappa}B activation provides a prosurvival response to radiation that may account for development of radioresistance. Curcumin blocks this signaling pathway and potentiates the antitumor effects of radiation therapy.« less

  2. Application of the kappa-omega Turbulence Model to Quasi-Three-Dimensional Turbomachinery Flows

    NASA Technical Reports Server (NTRS)

    Chima, Rodrick V.

    1996-01-01

    Many computational fluid dynamics codes for turbomachinery use the Baldwin-Lomax (B-L) turbulence model. It is easy to implement in two dimensions and works well for predicting overall turbomachinery performance. However, it is awkward to implement in three dimensions, often has difficulty finding the length scale, has a crude transition model, and neglects freestream turbulence, surface roughness, and mass injection. The kappa-omega model developed by Wilcox is an appealing alternative for several reasons. First, it is the only two-equation model that can be integrated to the wall without requiring damping functions or the distance to the wall, and hence, should behave well numerically. Second, the effects of freestream turbulence, surface roughness, and mass injection are easily included in the model. Finally, transition can be simulated using the low Reynolds number version of the model. Menter applied the kappa-model to external flows and showed very good results for flows with adverse pressure gradients. Liu and Zheng described their implementation of the kappa-model in a cascade code that included an area change term to account for endwall convergence. They validated the model for a flat plate, and compared the B-L and kappa-models to measured surface pressures for a low-pressure turbine cascade. Since they did not use the low Reynolds number version of the model, their results showed problems resulting from early transition. In this Note the low Reynolds number kappa-model was incorporated in the author's quasi-three-dimensional turbomachinery analysis code. The code includes the effects of rotation, radius change, and stream-surface thickness variation, and also includes the B-L turbulence model. The kappa-omega model was implemented using many of Menter's recommendations and an implicit approximate-factorization scheme described by Baldwin and Barth. The model was tested for a transonic compressor with rotation and variable stream-surface radius and height

  3. Pim-2 activates API-5 to inhibit the apoptosis of hepatocellular carcinoma cells through NF-kappaB pathway.

    PubMed

    Ren, Ke; Zhang, Wei; Shi, Yujun; Gong, Jianping

    2010-06-01

    Pim-2 is proved to be relevant to the tumorigenesis of hepatocellular carcinoma (HCC), but the mechanism is unclear. We studied the relationship among Pim-2, NF-kappaB and API-5. In our experiment, expression level of the three factors and phosphorylation level of API-5, as well as NF-kappaB activity, were detected in HCC tissues and the nontumorous controls. Then Pim-2 gene was transfected into nontumorous liver cells L02, and Pim-2 SiRNA was transfected into hepatoblastoma cell line HepG2. Parthenolide was added as NF-kappaB inhibitor. The same detections as above were repeated in the cells, along with the apoptosis analysis. We found the levels of Pim-2, NF-kappaB and API-5, as well as NF-kappaB activity, were significantly higher in HCC tissues. Pim-2 level was increased in L02 cells after the transfection of Pim-2 gene, but decreased in HepG2 cells after the transfection of Pim-2 SiRNA. The levels of NF-kappaB and API-5, as well as NF-kappaB activity and API-5 phosphorylation level, were in accordance with Pim-2 level, but could be reversed by Parthenolide. Cell apoptosis rates were negatively correlated with API-5 phosphorylation level. Therefore, we infer that Pim-2 could activate API-5 to inhibit the apoptosis of liver cells, and NF-kappaB is the key regulator.

  4. Formation of electron energy spectra during magnetic reconnection in laser-produced plasma

    NASA Astrophysics Data System (ADS)

    Huang, Kai; Lu, Quanming; Huang, Can; Dong, Quanli; Wang, Huanyu; Fan, Feibin; Sheng, Zhengming; Wang, Shui; Zhang, Jie

    2017-10-01

    Energetic electron spectra formed during magnetic reconnection between two laser-produced plasma bubbles are investigated by the use of two-dimensional particle-in-cell simulations. It is found that the evolution of such an interaction between the two plasma bubbles can be separated into two distinct stages: squeezing and reconnection stages. In the squeezing stage, when the two plasma bubbles expand quickly and collide with each other, the magnetic field in the inflow region is greatly enhanced. In the second stage, a thin current sheet is formed between the two plasma bubbles, and then, magnetic reconnection occurs therein. During the squeezing stage, electrons are heated in the perpendicular direction by betatron acceleration due to the enhancement of the magnetic field around the plasma bubbles. Meanwhile, non-thermal electrons are generated by the Fermi mechanism when these electrons bounce between the two plasma bubbles approaching quickly and get accelerated mainly by the convective electric field associated with the plasma bubbles. During the reconnection stage, electrons get further accelerated mainly by the reconnection electric field in the vicinity of the X line. When the expanding speed of the plasma bubbles is sufficiently large, the formed electron energy spectra have a kappa distribution, where the lower energy part satisfies a Maxwellian function and the higher energy part is a power-law distribution. Moreover, the increase in the expanding speed will result in the hardening of formed power-law spectra in both the squeezing and reconnection stages.

  5. Transmission of ˜ 10 keV electron beams through thin ceramic foils: Measurements and Monte Carlo simulations of electron energy distribution functions

    NASA Astrophysics Data System (ADS)

    Morozov, A.; Heindl, T.; Skrobol, C.; Wieser, J.; Krücken, R.; Ulrich, A.

    2008-07-01

    Electron beams with particle energy of ~10 keV were sent through 300 nm thick ceramic (Si3N4 + SiO2) foils and the resulting electron energy distribution functions were recorded using a retarding grid technique. The results are compared with Monte Carlo simulations performed with two publicly available packages, Geant4 and Casino v2.42. It is demonstrated that Geant4, unlike Casino, provides electron energy distribution functions very similar to the experimental distributions. Both simulation packages provide a quite precise average energy of transmitted electrons: we demonstrate that the maximum uncertainty of the calculated values of the average energy is 6% for Geant4 and 8% for Casino, taking into account all systematic uncertainties and the discrepancies in the experimental and simulated data.

  6. (/sup 3/H)Ethylketocyclazocine binding to mouse brain membranes: evidence for a kappa opioid receptor type

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Garzon, J.; Sanchez-Blazquez, P.; Lee, N.M.

    1984-10-01

    The binding of the putative kappa agonist ethylketocyclazocine (EKC) to synaptosomal membranes of mouse brain was studied. This benzomorphan was able to bind to different opioid receptors. A portion of this binding was not inhibited by the agonist naloxone, even at high concentrations (10 microM). This population of receptors, to which opioate alkaloids and opiod peptides display very low affinity, is probably the sigma receptor. Another class of binding sites was identified by the simultaneous addition of the selective agonists Sandoz FK-33824 and D-Ala2-D-Leu5-enkephalin, which blocked the access of EKC to mu and delta opioid receptors, respectively, leaving a portionmore » of naloxone-displaceable benzomorphan binding still detectable. Analysis of this remaining binding revealed a small population of receptors of high affinity, the kappa receptor. Therefore, EKC binds to the mu, delta, kappa and sigma receptors in the mouse brain, with similar affinities for the mu and kappa (0.22 and 0.15 nM). These results confirm the existence of a kappa opioid receptor type in the mouse brain.« less

  7. Suprathermal plasma analyzer for the measurement of low-energy electron distribution in the ionosphere.

    PubMed

    Shimoyama, M; Oyama, K-I; Abe, T; Yau, A W

    2011-07-01

    It is commonly believed that an energy transfer from thermal to suprathermal electrons (electron energy spectrum in this energy range is quite limited because of technical difficulties of measurement. We have developed an instrument to measure electron energy distribution from thermal to suprathermal energy continuously with high-energy resolution of about 0.15 eV. The measurement principle is based on the combination of a retarding potential analyzer with a channel electron multiplier (CEM) and the Druyvesteyn method, which derives energy distribution from the current-voltage characteristics. The capability of detecting plasma space potential enables absolute calibration of electron energy. The instrument with a small vacuum pump, which is required for the CEM to work in low-vacuum region, was first successfully tested by a sounding rocket S-310-37 in the ionospheric E region. The instrument is expected to provide new opportunities to measure energy distribution of thermal and non-thermal electrons in low-density plasma, where a Langmuir probe cannot measure electron temperature because of low plasma density.

  8. The Role of the Noncanonical NF-KappaB Pathway in Colon Cancer

    DTIC Science & Technology

    2016-08-01

    AWARD NUMBER: W81XWH-13-1-0321 TITLE: The Role of the Noncanonical NF -KappaB Pathway in Colon Cancer PRINCIPAL INVESTIGATOR: Yatrik Shah...2013 - 29 May 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-13-1-0321 The Role of the Noncanonical NF -KappaB Pathway in Colon Cancer 5b...inflammatory bowel disease samples that the non-canonical NF -κB2 signaling cascade is highly activated in intestinal epithelial cells compared to normal

  9. Polarization of photons scattered by electrons in any spectral distribution

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chang, Zhe; Lin, Hai-Nan; Jiang, Yunguo, E-mail: jiangyg@ihep.ac.cn

    On the basis of the quantum electrodynamics, we present a generic formalism of the polarization for beamed monochromatic photons scattered by electrons in any spectral distribution. The formulae reduce to the components of the Fano matrix when electrons are at rest. We mainly investigate the polarization in three scenarios, i.e., electrons at rest, isotropic electrons with a power-law spectrum, and thermal electrons. If the incident beam is polarized, the polarization is reduced significantly by isotropic electrons at large viewing angles; the degree of polarization caused by thermal electrons is about half of that caused by power-law electrons. If the incidentmore » bean is unpolarized, soft γ-rays can lead to about 15% polarization at viewing angles around π/4. For isotropic electrons, one remarkable feature is that the polarization as a function of the incident photon energy always peaks roughly at 1 MeV; this is valid for both the thermal and power-law cases. This feature can be used to distinguish the model of the inverse Compton scattering from that of the synchrotron radiation.« less

  10. Spacecraft Observations and Analytic Theory of Crescent-Shaped Electron Distributions in Asymmetric Magnetic Reconnection

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Egedal, J.; Le, A.; Daughton, W.

    Supported by a kinetic simulation, we derive in this paper an exclusion energy parametermore » $${\\mathcal{E}}_{X}$$ providing a lower kinetic energy bound for an electron to cross from one inflow region to the other during magnetic reconnection. As by a Maxwell demon, only high-energy electrons are permitted to cross the inner reconnection region, setting the electron distribution function observed along the low-density side separatrix during asymmetric reconnection. Finally, the analytic model accounts for the two distinct flavors of crescent-shaped electron distributions observed by spacecraft in a thin boundary layer along the low-density separatrix.« less

  11. Spacecraft Observations and Analytic Theory of Crescent-Shaped Electron Distributions in Asymmetric Magnetic Reconnection

    DOE PAGES

    Egedal, J.; Le, A.; Daughton, W.; ...

    2016-10-24

    Supported by a kinetic simulation, we derive in this paper an exclusion energy parametermore » $${\\mathcal{E}}_{X}$$ providing a lower kinetic energy bound for an electron to cross from one inflow region to the other during magnetic reconnection. As by a Maxwell demon, only high-energy electrons are permitted to cross the inner reconnection region, setting the electron distribution function observed along the low-density side separatrix during asymmetric reconnection. Finally, the analytic model accounts for the two distinct flavors of crescent-shaped electron distributions observed by spacecraft in a thin boundary layer along the low-density separatrix.« less

  12. Tumor necrosis factor alpha induces gamma-glutamyltransferase expression via nuclear factor-kappaB in cooperation with Sp1.

    PubMed

    Reuter, Simone; Schnekenburger, Michael; Cristofanon, Silvia; Buck, Isabelle; Teiten, Marie-Hélène; Daubeuf, Sandrine; Eifes, Serge; Dicato, Mario; Aggarwal, Bharat B; Visvikis, Athanase; Diederich, Marc

    2009-02-01

    Gamma-glutamyltransferase (GGT) cleaves the gamma-glutamyl moiety of glutathione (GSH), an endogenous antioxidant, and is involved in mercapturic acid metabolism and in cancer drug resistance when overexpressed. Moreover, GGT converts leukotriene (LT) C4 into LTD4 implicated in various inflammatory pathologies. So far the effect of inflammatory stimuli on regulation of GGT expression and activity remained to be addressed. We found that the proinflammatory cytokine tumor necrosis factor alpha (TNFalpha) induced GGT promoter transactivation, mRNA and protein synthesis, as well as enzymatic activity. Remicade, a clinically used anti-TNFalpha antibody, small interfering RNA (siRNA) against p50 and p65 nuclear factor-kappaB (NF-kappaB) isoforms, curcumin, a well characterized natural NF-kappaB inhibitor, as well as a dominant negative inhibitor of kappaB alpha (IkappaBalpha), prevented GGT activation at various levels, illustrating the involvement of this signaling pathway in TNFalpha-induced stimulation. Over-expression of receptor of TNFalpha-1 (TNFR1), TNFR-associated factor-2 (TRAF2), TNFR-1 associated death domain (TRADD), dominant negative (DN) IkappaBalpha or NF-kappaB p65 further confirmed GGT promoter activation via NF-kappaB. Linker insertion mutagenesis of 536 bp of the proximal GGT promoter revealed NF-kappaB and Sp1 binding sites at -110 and -78 relative to the transcription start site, responsible for basal GGT transcription. Mutation of the NF-kappaB site located at -110 additionally inhibited TNFalpha-induced promoter induction. Chromatin immunoprecipitation (ChIP) assays confirmed mutagenesis results and further demonstrated that TNFalpha treatment induced in vivo binding of both NF-kappaB and Sp1, explaining increased GGT expression, and led to RNA polymerase II recruitment under inflammatory conditions.

  13. Analysis on IGBT and Diode Failures in Distribution Electronic Power Transformers

    NASA Astrophysics Data System (ADS)

    Wang, Si-cong; Sang, Zi-xia; Yan, Jiong; Du, Zhi; Huang, Jia-qi; Chen, Zhu

    2018-02-01

    Fault characteristics of power electronic components are of great importance for a power electronic device, and are of extraordinary importance for those applied in power system. The topology structures and control method of Distribution Electronic Power Transformer (D-EPT) are introduced, and an exploration on fault types and fault characteristics for the IGBT and diode failures is presented. The analysis and simulation of different fault types for the fault characteristics lead to the D-EPT fault location scheme.

  14. Rogue Waves in Multi-Ion Cometary Plasmas

    NASA Astrophysics Data System (ADS)

    Sreekala, G.; Manesh, M.; Neethu, T. W.; Anu, V.; Sijo, S.; Venugopal, C.

    2018-01-01

    The effect of pair ions on the formation of rogue waves in a six-component plasma composed of two hot and one colder electron component, hot ions, and pair ions is studied. The kappa distribution, which provides an unambiguous replacement for a Maxwellian distribution in space plasmas, is connected with nonextensive statistical mechanics and provides a continuous energy spectrum. Hence, the colder and one component of the hotter electrons is modeled by kappa distributions and the other hot electron component, by a q-nonextensive distribution. It is found that the rogue wave amplitude is different for various pair-ion components. The magnitude, however, increases with increasing spectral index and nonextensive parameter q. These results may be useful in understanding the basic characteristics of rogue waves in cometary plasmas.

  15. Neutrality of the canonical NF-kappaB-dependent pathway for human and murine cytomegalovirus transcription and replication in vitro.

    PubMed

    Benedict, Chris A; Angulo, Ana; Patterson, Ginelle; Ha, Sukwon; Huang, Huang; Messerle, Martin; Ware, Carl F; Ghazal, Peter

    2004-01-01

    Cytomegalovirus (CMV) is known to rapidly induce activation of nuclear factor kappaB (NF-kappaB) after infection of fibroblast and macrophage cells. NF-kappaB response elements are present in the enhancer region of the CMV major immediate-early promoter (MIEP), and activity of the MIEP is strongly upregulated by NF-kappaB in transient-transfection assays. Here we investigate whether the NF-kappaB-dependent pathway is required for initiating or potentiating human and murine CMV replication in vitro. We show that expression of a dominant negative mutant of the inhibitor of NF-kappaB-alpha (IkappaBalphaM) does not alter the replication kinetics of human or mouse CMV in cultured cells. In addition, mouse embryo fibroblasts genetically deficient for p65/RelA actually showed elevated levels of MCMV replication. Mutation of all NF-kappaB response elements within the enhancer of the MIEP in a recombinant mouse CMV containing the human MIEP (hMCMV-ES), which we have previously shown to replicate in murine fibroblasts with kinetics equivalent to that of wild-type mouse CMV, did not negatively affect replication in fibroblasts. Taken together, these data show that, for CMV replication in cultured fibroblasts activation of the canonical NF-kappaB pathway and binding of NF-kappaB to the MIEP are dispensable, and in the case of p65 may even interfere, thus uncovering a previously unrecognized level of complexity in the host regulatory network governing MIE gene expression in the context of a viral infection.

  16. Electron energy distribution in a helium plasma created by nuclear radiations

    NASA Technical Reports Server (NTRS)

    Lo, R. H.; Miley, G. H.

    1974-01-01

    An integral balance technique for calculation of the electron energy distribution in a radiation-induced plasma is described. Results predict W-values reasonably well and compare favorably with more complicated Monte-Carlo calculations. The distribution found differs from that in a normal electrical discharge and is of interest in radiation-pumped laser research.

  17. A positive correlation between energetic electron butterfly distributions and magnetosonic waves in the radiation belt slot region

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yang, Chang; Su, Z.; Xiao, F.

    Energetic (hundreds of keV) electrons in the radiation belt slot region have been found to exhibit the butterfly pitch angle distributions. Resonant interactions with magnetosonic and whistler-mode waves are two potential mechanisms for the formation of these peculiar distributions. Here we perform a statistical study of energetic electron pitch angle distribution characteristics measured by Van Allen Probes in the slot region during a three-year period from May 2013 to May 2016. Our results show that electron butterfly distributions are closely related to magnetosonic waves rather than to whistlermode waves. Both electron butterfly distributions and magnetosonic waves occur more frequently atmore » the geomagnetically active times than at the quiet times. In a statistical sense, more distinct butterfly distributions usually correspond to magnetosonic waves with larger amplitudes and vice versa. The averaged magnetosonic wave amplitude is less than 5 pT in the case of normal and flat-top distributions with a butterfly index BI = 1 but reaches ~ 35–95 pT in the case of distinct butterfly distributions with BI > 1:3. For magnetosonic waves with amplitudes > 50 pT, the occurrence rate of butterfly distribution is above 80%. Our study suggests that energetic electron butterfly distributions in the slot region are primarily caused by magnetosonic waves.« less

  18. A positive correlation between energetic electron butterfly distributions and magnetosonic waves in the radiation belt slot region

    DOE PAGES

    Yang, Chang; Su, Z.; Xiao, F.; ...

    2017-05-14

    Energetic (hundreds of keV) electrons in the radiation belt slot region have been found to exhibit the butterfly pitch angle distributions. Resonant interactions with magnetosonic and whistler-mode waves are two potential mechanisms for the formation of these peculiar distributions. Here we perform a statistical study of energetic electron pitch angle distribution characteristics measured by Van Allen Probes in the slot region during a three-year period from May 2013 to May 2016. Our results show that electron butterfly distributions are closely related to magnetosonic waves rather than to whistlermode waves. Both electron butterfly distributions and magnetosonic waves occur more frequently atmore » the geomagnetically active times than at the quiet times. In a statistical sense, more distinct butterfly distributions usually correspond to magnetosonic waves with larger amplitudes and vice versa. The averaged magnetosonic wave amplitude is less than 5 pT in the case of normal and flat-top distributions with a butterfly index BI = 1 but reaches ~ 35–95 pT in the case of distinct butterfly distributions with BI > 1:3. For magnetosonic waves with amplitudes > 50 pT, the occurrence rate of butterfly distribution is above 80%. Our study suggests that energetic electron butterfly distributions in the slot region are primarily caused by magnetosonic waves.« less

  19. Inhibition of IL-1{beta}-mediated inflammatory responses by the I{kappa}B{alpha} super-repressor in human fibroblast-like synoviocytes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lee, Young-Rae; Kweon, Suc-Hyun; Kwon, Kang-Beom

    The IL-1{beta}-NF-{kappa}B axis is a key pathway in the pathogenesis of rheumatoid arthritis (RA) and is central in the production of proinflammatory mediators in the inflamed synovium. Therefore, we examined whether fibroblast-like synoviocytes (FLS) could be spared from IL-1{beta}-induced toxicity by an overexpressing I{kappa}B super-repressor. Infection of FLS with Ad-I{kappa}B{alpha} (S32A, S36A), an adenovirus-containing mutant I{kappa}B{alpha}, inhibited IL-1{beta}-induced nuclear translocation and DNA binding of NF-{kappa}B. In addition, Ad-I{kappa}B{alpha} (S32A, S36A) prevented IL-1{beta}-induced inflammatory responses; namely, the production of chemokines, such as ENA-78 and RANTES, and activation of MMP-1 and MMP-3. Finally, increased cellular proliferation of FLS after IL-1{beta} treatment wasmore » significantly reduced by Ad-I{kappa}B{alpha} (S32A, S36A). However, Ad-I{kappa}B{beta} (S19A, S23A), the I{kappa}B{beta} mutant, was not effective in preventing IL-1{beta} toxicity. These results suggest that inhibition of I{kappa}B{alpha} degradation is a potential target for the prevention of joint destruction in patients with RA.« less

  20. Transcription factor NF-kappaB regulates inducible CD83 gene expression in activated T lymphocytes.

    PubMed

    McKinsey, T A; Chu, Z; Tedder, T F; Ballard, D W

    2000-01-01

    The immunoglobulin superfamily member CD83 is expressed on the surface of mature dendritic cells that present processed antigens to T lymphocytes. In addition, T cells acquire CD83 expression following mitogenic stimulation in vitro. Here we report two lines of evidence demonstrating that this inducible lymphocyte response is genetically programmed by transcription factor NF-kappaB and contingent upon proteolytic breakdown of its cytoplasmic inhibitor IkappaBalpha. First, signal-dependent induction of CD83 mRNA expression is blocked in both transformed and primary T cells harboring a degradation-resistant mutant of IkappaBalpha that constitutively represses NF-kappaB. Second, as revealed in gel retardation assays, the IkappaBalpha constitutive repressor prevents the inducible interaction of NF-kappaB with consensus recognition sites identified in the CD83 promoter. Given that IkappaBalpha is functionally coupled to the T-cell antigen receptor, these findings suggest that the downstream transcription unit for CD83 is triggered by NF-kappaB during an adaptive immune response.

  1. Electron beam machining using rotating and shaped beam power distribution

    DOEpatents

    Elmer, John W.; O'Brien, Dennis W.

    1996-01-01

    An apparatus and method for electron beam (EB) machining (drilling, cutting and welding) that uses conventional EB guns, power supplies, and welding machine technology without the need for fast bias pulsing technology. The invention involves a magnetic lensing (EB optics) system and electronic controls to: 1) concurrently bend, focus, shape, scan, and rotate the beam to protect the EB gun and to create a desired effective power-density distribution, and 2) rotate or scan this shaped beam in a controlled way. The shaped beam power-density distribution can be measured using a tomographic imaging system. For example, the EB apparatus of this invention has the ability to drill holes in metal having a diameter up to 1000 .mu.m (1 mm or larger), compared to the 250 .mu.m diameter of laser drilling.

  2. The angular distribution of solar wind ˜20-200 keV superhalo electrons at quiet times

    NASA Astrophysics Data System (ADS)

    Yang, Liu; Wang, Linghua; Li, Gang; He, Jiansen; Salem, Chadi S.; Tu, Chuanyi; Wimmer-Schweingruber, Robert F.; Bale, Stuart D.

    2016-03-01

    We present a comprehensive study of the angular distribution of ˜20-200 keV superhalo electrons measured at 1 AU by the WIND 3DP instrument during quiet times from 1995 January through 2005 December. According to the interplanetary magnetic field, we re-bin the observed electron pitch angle distributions to obtain the differential flux, Jout (Jin), of electrons traveling outward from (inward toward) the Sun, and define the anisotropy of superhalo electrons as A =2/(Jo u t-Ji n) Jo u t+Ji n at a given energy. We found that for out in ˜96% of the selected quiet-time samples, superhalo electrons have isotropic angular distributions, while for ˜3% (˜1%) of quiet-time samples, superhalo electrons are outward-anisotropic (inward-anisotropic). All three groups of angular distributions show no correlation with the local solar wind plasma, interplanetary magnetic field and turbulence. Furthermore, the superhalo electron spectral index shows no correlation with the spectral index of local solar wind turbulence. These quiet-time superhalo electrons may be accelerated by nonthermal processes related to the solar wind source and strongly scattered/ reflected in the interplanetary medium, or could be formed due to the electron acceleration through the interplanetary medium.

  3. Collision-energy-resolved angular distribution of Penning electrons for N 2-He ∗(2 3S)

    NASA Astrophysics Data System (ADS)

    Hanzawa, Yoshinori; Kishimoto, Naoki; Yamazaki, Masakazu; Ohno, Koichi

    2006-07-01

    The collision-energy-resolved angular distributions of Penning electrons for individual ionic state of N 2-He ∗(2 3S) were measured. The angular distributions showed increasing intensity in the backward (rebounding) directions with respect to initial He ∗(2 3S) beam vector because Penning ionization occurs with a collision against repulsive interaction wall followed by the electron emission from 2s orbital of He ∗. We also analyzed internal angular distribution by means of fitting parameters using classical trajectory calculations for N 2-He ∗(2 3S) on the modified interaction potential. These internal angular distributions suggested the electron emission from 2s orbital of He ∗ and they depended on collision energy and electron kinetic energy.

  4. Electrostatic waves driven by electron beam in lunar wake plasma

    NASA Astrophysics Data System (ADS)

    Sreeraj, T.; Singh, S. V.; Lakhina, G. S.

    2018-05-01

    A linear analysis of electrostatic waves propagating parallel to the ambient field in a four component homogeneous, collisionless, magnetised plasma comprising fluid protons, fluid He++, electron beam, and suprathermal electrons following kappa distribution is presented. In the absence of electron beam streaming, numerical analysis of the dispersion relation shows six modes: two electron acoustic modes (modes 1 and 6), two fast ion acoustic modes (modes 2 and 5), and two slow ion acoustic modes (modes 3 and 4). The modes 1, 2 and 3 and modes 4, 5, and 6 have positive and negative phase speeds, respectively. With an increase in electron beam speed, the mode 6 gets affected the most and the phase speed turns positive from negative. The mode 6 thus starts to merge with modes 2 and 3 and generates the electron beam driven fast and slow ion acoustic waves unstable with a finite growth. The electron beam driven slow ion-acoustic waves occur at lower wavenumbers, whereas fast ion-acoustic waves occur at a large value of wavenumbers. The effect of various other parameters has also been studied. We have applied this analysis to the electrostatic waves observed in lunar wake during the first flyby of the ARTEMIS mission. The analysis shows that the low (high) frequency waves observed in the lunar wake could be the electron beam driven slow (fast) ion-acoustic modes.

  5. Expression and localization of peroxisome proliferator-activated receptors and nuclear factor kappaB in normal and lesional psoriatic skin.

    PubMed

    Westergaard, Majken; Henningsen, Jeanette; Johansen, Claus; Rasmussen, Sofie; Svendsen, Morten Lyhne; Jensen, Uffe Birk; Schrøder, Henrik Daa; Staels, Bart; Iversen, Lars; Bolund, Lars; Kragballe, Knud; Kristiansen, Karsten

    2003-11-01

    Abnormal epidermal proliferation and differentiation characterize the inflammatory skin disease psoriasis. Here we demonstrate that expression of PPARdelta mRNA and protein is markedly upregulated in psoriatic lesions and that lipoxygenase products accumulating in psoriatic lesions are potent activators of PPARdelta. The expression levels of NF-kappaB p50 and p65 were not significantly altered in lesional compared with nonlesional psoriatic skin. In the basal layer of normal epidermis both p50 and p65 were sequestered in the cytoplasm, whereas p50, but not p65, localized to nuclei in the suprabasal layers, and this distribution was maintained in lesional psoriatic skin. In normal human keratinocytes PPAR agonists neither impaired IL-1beta-induced translocation of p65 nor IL-1beta-induced NF-kappaB DNA binding. We show that PPARdelta physically interacts with the N-terminal Rel homology domain of p65. Irrespective of the presence of agonists none of the PPAR subtypes decreased p65-mediated transactivation in keratinocytes. In contrast p65, but not p50, was a potent repressor of PPAR-mediated transactivation. The p65-dependent repression of PPARdelta- but not PPARalpha- or PPARgamma-mediated transactivation was partially relieved by forced expression of the coactivators p300 or CBP. We suggest that deficient NF-kappaB activation in chronic psoriatic plaques permitting unabated PPARdelta-mediated transactivation contributes to the pathologic phenotype of psoriasis.

  6. DE 1 and Viking observations associated with electron conical distributions

    NASA Technical Reports Server (NTRS)

    Menietti, J. D.; Weimer, D. R.; Andre, M.; Eliasson, L.

    1994-01-01

    Data from the electron detectors on board the Swedish Viking satellite launched during a period of low solar activity and from the Dynamic Explorer (DE) 1 satellite launched during active solar coditions have been examined for the occurrence and location of electron conical distributions and several conclusions can be drawn. First, we note that most of the best examples of electron conics observed by the V-3 experiment onboard Viking occurred in the afternoon sector in the range of magneitc local time 14 hours less than Magnetic Local Time (MLT) less than 18 hours, at midaltitudes in the range 10,000 km less than h less than 13,500 km, with few occurring in the nightside auroral region, a region poorly sampled at altitudes greater than 5000 km. For the Viking data there is an association of electron conics with upper hybrid waves. DE 1 observations made by the high-altitude plasma instrument (HAPI) indicate that electron conics were observed in the midmorning sector and the late evening sector, and as has been reported earlier, the correlation with upper hybird waves was good. The HAPI did not sample the afternoon sector. The electon conics observed on both satellites occurred in the presence of at least a modest (several kilovolts) potential difference beneath the satellite with a maximum energy that was usually, but not always, equal to or greater than the maximum energy of the electron conics. Two independent sets of observations by DE 1 suggest two distinct production mechanisms for electron conics. Examiniation of DE 1 electric field measurements from the plasma wave instrument during the observation of electron conics show simultaneous parallel oscillations in the frequency range of 0.2 Hz less than f less than 0.5 Hz during one and perhaps two of four events examined, and upper hybrid waves were observed on all four events. In addition, recent observations of '90-deg' electron conics associated with auroral kilometric radiation source regions suggest a

  7. Effects of Cot expression on the nuclear translocation of NF-kappaB in RBL-2H3 cells.

    PubMed

    Chikamatsu, Satomi; Furuno, Tadahide; Kinoshita, Yosuke; Inoh, Yoshikazu; Hirashima, Naohide; Teshima, Reiko; Nakanishi, Mamoru

    2007-03-01

    Cot is a serine/threonine protein kinase and is classified as a mitogen-activated protein (MAP) kinase kinase kinase. Overexpression of this protein has been shown to activate the extracellular signal-regulated kinase, the c-Jun N-terminal kinase, and the p38 MAP kinase pathways and to stimulate NF-AT and NF-kappaB-dependent transcription. Here we have shown that Cot kinase activity is intimately involved in the high affinity receptor for IgE (FcvarepsilonRI)-mediated nuclear translocation of NF-kappaB1 independent of NF-kappaB-inducing kinase (NIK) in rat basophilic leukemia (RBL-2H3) cells. A transfected green fluorescent protein-tagged NF-kappaB1 (GFP-NF-kappaB1) resided in the cytoplasm in RBL-2H3 cells and it remained in the cytoplasm even when Cot tagged with red fluorescent protein (Cot-RFP) was co-expressed. Western blotting analysis showed that IkappaB kinases (IKKs) were expressed in RBL-2H3 cells but NIK was not. GFP-NF-kappaB1 translocated from the cytoplasm to the nucleus after the aggregation of FcvarepsilonRI in Cot-transfected cells but not in kinase-deficient Cot-transfected cells. This finding gives a new insight into the role of Cot in the FcvarepsilonRI-mediated NF-kappaB activation in mast cells.

  8. The Earth's Thorium and Uranium Abundance and Distribution

    NASA Astrophysics Data System (ADS)

    McDonough, W. F.; Guo, M.; Wipperfurth, S. A.

    2017-12-01

    The abundance and distribution of thorium (Th) and uranium (U) and its Th/U value have been assessed for the bulk silicate Earth (BSE), core, modern mantle and continental crust. These heat producing elements power the Earth's engine and are recorders of atmospheric oxidation and biologically mediated processes. More than 50,000 measured Th/U values (Kappa) and a couple of thousand Kappa-Pb values, the time-integrated Pb isotopic values from the decay of Th and U, are evaluated for the BSE, continental crust (CC) and modern mantle (MM), with the latter represented by mid-ocean ridge basalts (MORB) and ocean island basalt (OIB). The Kappa-Pb values for these complementary enriched and depleted domains of the BSE (i.e., CC_Kappa-Pb = 4.1 +/- 0.2 and MM_Kappa-Pb = 3.8 +/- 0.1, respectively) narrowly bracket the solar system initial (SSi_Kappa-Pb = 3.88 +/- 0.02) with an uncertainty of +/-5%) and demonstrate that negligible Th/U fractionation accompanied accretion, core formation, and crust - mantle differentiation. Experimental studies find marked differences in the partitioning of U and Th during core formation and thus, the BSE_Kappa-Pb = of 3.9 +/- 0.2 dictates that Th and U were excluded from the core. The <4% differences between the CC_Kappa-Pb and MM_Kappa-Pb reveals that U6+ recycling back into the mantle has either been a relatively recent process or that its recycling following atmospheric oxygenation at 2.4 Ga was limited and evolved slowly with time. Recent data from geoneutrino flux measurements at KamLAND observes a Th/U of 4.1 (+5.5, -3.3); although these uncertainties are large, future experiments, with annual count rates that are 10 to 40 times greater than that at KamLAND, will provide greater statistics, a critical measure of the planetary Th/U ratio, and an assessment of the assumption of chondritic ratio for the Earth.

  9. Quantum tunneling recombination in a system of randomly distributed trapped electrons and positive ions.

    PubMed

    Pagonis, Vasilis; Kulp, Christopher; Chaney, Charity-Grace; Tachiya, M

    2017-09-13

    During the past 10 years, quantum tunneling has been established as one of the dominant mechanisms for recombination in random distributions of electrons and positive ions, and in many dosimetric materials. Specifically quantum tunneling has been shown to be closely associated with two important effects in luminescence materials, namely long term afterglow luminescence and anomalous fading. Two of the common assumptions of quantum tunneling models based on random distributions of electrons and positive ions are: (a) An electron tunnels from a donor to the nearest acceptor, and (b) the concentration of electrons is much lower than that of positive ions at all times during the tunneling process. This paper presents theoretical studies for arbitrary relative concentrations of electrons and positive ions in the solid. Two new differential equations are derived which describe the loss of charge in the solid by tunneling, and they are solved analytically. The analytical solution compares well with the results of Monte Carlo simulations carried out in a random distribution of electrons and positive ions. Possible experimental implications of the model are discussed for tunneling phenomena in long term afterglow signals, and also for anomalous fading studies in feldspars and apatite samples.

  10. An essential complementary role of NF-kappaB pathway to microbicidal oxidants in Drosophila gut immunity.

    PubMed

    Ryu, Ji-Hwan; Ha, Eun-Mi; Oh, Chun-Taek; Seol, Jae-Hong; Brey, Paul T; Jin, Ingnyol; Lee, Dong Gun; Kim, Jaesang; Lee, Daekee; Lee, Won-Jae

    2006-08-09

    In the Drosophila gut, reactive oxygen species (ROS)-dependent immunity is critical to host survival. This is in contrast to the NF-kappaB pathway whose physiological function in the microbe-laden epithelia has yet to be convincingly demonstrated despite playing a critical role during systemic infections. We used a novel in vivo approach to reveal the physiological role of gut NF-kappaB/antimicrobial peptide (AMP) system, which has been 'masked' in the presence of the dominant intestinal ROS-dependent immunity. When fed with ROS-resistant microbes, NF-kappaB pathway mutant flies, but not wild-type flies, become highly susceptible to gut infection. This high lethality can be significantly reduced by either re-introducing Relish expression to Relish mutants or by constitutively expressing a single AMP to the NF-kappaB pathway mutants in the intestine. These results imply that the local 'NF-kappaB/AMP' system acts as an essential 'fail-safe' system, complementary to the ROS-dependent gut immunity, during gut infection with ROS-resistant pathogens. This system provides the Drosophila gut immunity the versatility necessary to manage sporadic invasion of virulent pathogens that somehow counteract or evade the ROS-dependent immunity.

  11. Electron energy distribution function in the divertor region of the COMPASS tokamak during neutral beam injection heating

    NASA Astrophysics Data System (ADS)

    Hasan, E.; Dimitrova, M.; Havlicek, J.; Mitošinková, K.; Stöckel, J.; Varju, J.; Popov, Tsv K.; Komm, M.; Dejarnac, R.; Hacek, P.; Panek, R.; the COMPASS Team

    2018-02-01

    This paper presents the results from swept probe measurements in the divertor region of the COMPASS tokamak in D-shaped, L-mode discharges, with toroidal magnetic field BT = 1.15 T, plasma current Ip = 180 kA and line-average electron densities varying from 2 to 8×1019 m-3. Using neutral beam injection heating, the electron energy distribution function is studied before and during the application of the beam. The current-voltage characteristics data are processed using the first-derivative probe technique. This technique allows one to evaluate the plasma potential and the real electron energy distribution function (respectively, the electron temperatures and densities). At the low average electron density of 2×1019 m-3, the electron energy distribution function is bi-Maxwellian with a low-energy electron population with temperatures 4-6 eV and a high-energy electron group 12-25 eV. As the line-average electron density is increased, the electron temperatures decrease. At line-average electron densities above 7×1019 m-3, the electron energy distribution function is found to be Maxwellian with a temperature of 6-8.5 eV. The effect of the neutral beam injection heating power in the divertor region is also studied.

  12. Induction of nuclear factor kappaB by the CD30 receptor is mediated by TRAF1 and TRAF2.

    PubMed Central

    Duckett, C S; Gedrich, R W; Gilfillan, M C; Thompson, C B

    1997-01-01

    CD30 is a lymphoid cell-specific surface receptor which was originally identified as an antigen expressed on Hodgkin's lymphoma cells. Activation of CD30 induces the nuclear factor kappaB (NF-kappaB) transcription factor. In this study, we define the domains in CD30 which are required for NF-kappaB activation. Two separate elements of the cytoplasmic domain which were capable of inducing NF-kappaB independently of one another were identified. The first domain (domain 1) mapped to a approximately 120-amino-acid sequence in the membrane-proximal region of the CD30 cytoplasmic tail, between residues 410 and 531. A second, more carboxy-terminal region (domain 2) was identified between residues 553 and 595. Domain 2 contains two 5- to 10-amino-acid elements which can mediate the binding of CD30 to members of the tumor necrosis factor receptor-associated factor (TRAF) family of signal transducing proteins. Coexpression of CD30 with TRAF1 or TRAF2 but not TRAF3 augmented NF-kappaB activation through domain 2 but not domain 1. NF-kappaB induction through domain 2 was inhibited by coexpression of either full-length TRAF3 or dominant negative forms of TRAF1 or TRAF2. In contrast, NF-kappaB induction by domain 1 was not affected by alterations in TRAF protein levels. Together, these data support a model in which CD30 can induce NF-kappaB by both TRAF-dependent and -independent mechanisms. TRAF-dependent induction of NF-kappaB appears to be regulated by the relative levels of individual TRAF proteins in the cell. PMID:9032281

  13. Effects of the reconnection electric field on crescent electron distribution functions in asymmetric guide field reconnection

    NASA Astrophysics Data System (ADS)

    Bessho, N.; Chen, L. J.; Hesse, M.; Wang, S.

    2017-12-01

    In asymmetric reconnection with a guide field in the Earth's magnetopause, electron motion in the electron diffusion region (EDR) is largely affected by the guide field, the Hall electric field, and the reconnection electric field. The electron motion in the EDR is neither simple gyration around the guide field nor simple meandering motion across the current sheet. The combined meandering motion and gyration has essential effects on particle acceleration by the in-plane Hall electric field (existing only in the magnetospheric side) and the out-of-plane reconnection electric field. We analyze electron motion and crescent-shaped electron distribution functions in the EDR in asymmetric guide field reconnection, and perform 2-D particle-in-cell (PIC) simulations to elucidate the effect of reconnection electric field on electron distribution functions. Recently, we have analytically expressed the acceleration effect due to the reconnection electric field on electron crescent distribution functions in asymmetric reconnection without a guide field (Bessho et al., Phys. Plasmas, 24, 072903, 2017). We extend the theory to asymmetric guide field reconnection, and predict the crescent bulge in distribution functions. Assuming 1D approximation of field variations in the EDR, we derive the time period of oscillatory electron motion (meandering + gyration) in the EDR. The time period is expressed as a hybrid of the meandering period and the gyro period. Due to the guide field, electrons not only oscillate along crescent-shaped trajectories in the velocity plane perpendicular to the antiparallel magnetic fields, but also move along parabolic trajectories in the velocity plane coplanar with magnetic field. The trajectory in the velocity space gradually shifts to the acceleration direction by the reconnection electric field as multiple bounces continue. Due to the guide field, electron distributions for meandering particles are bounded by two paraboloids (or hyperboloids) in the

  14. Convulsions may alter the specificity of kappa-opiate receptors.

    PubMed

    Mansour, A; Valenstein, E S

    1986-06-01

    Morphine, a mu-opiate agonist, and ethylketazocine, a kappa-opiate agonist, produce distinct behavioral, pharmacologic, and biochemical effects. In the mouse, large doses of morphine produce convulsions that are usually lethal and that cannot be blocked by naltrexone, whereas ethylketazocine produces nonlethal clonic convulsions that can be blocked by naltrexone. Moreover, mice made tolerant to morphine failed to show cross-tolerance to ethylketazocine, suggesting that the convulsions induced by these drugs are not mediated via a common opioid mechanism. Following a series of electroconvulsive shocks, both morphine and ethylketazocine produced clonic convulsions that were not lethal and that could be blocked by naltrexone. Furthermore, electroconvulsive shock-treated animals made tolerant to morphine-induced convulsions showed cross-tolerance to ethylketazocine. These data suggest that electroconvulsive shock may alter kappa-opioid systems in such a way as to allow mu-agonists to be functional at these sites.

  15. TLR3-mediated NF-{kappa}B signaling in human esophageal epithelial cells.

    PubMed

    Lim, Diana M; Narasimhan, Sneha; Michaylira, Carmen Z; Wang, Mei-Lun

    2009-12-01

    Despite its position at the front line against ingested pathogens, very little is presently known about the role of the esophageal epithelium in host innate immune defense. As a key player in the innate immune response, Toll-like receptor (TLR) signaling has not been well characterized in human esophageal epithelial cells. In the present study, we investigated the inflammatory response and signaling pathways activated by TLR stimulation of human esophageal cells in vitro. Using quantitative RT-PCR, we profiled the expression pattern of human TLRs 1-10 in primary esophageal keratinocytes (EPC2), immortalized nontransformed esophageal keratinocytes (EPC2-hTERT), and normal human esophageal mucosal biopsies and found that TLRs 1, 2, 3, and 5 were expressed both in vivo and in vitro. Using the cytokine IL-8 as a physiological read out of the inflammatory response, we found that TLR3 is the most functional of the expressed TLRs in both primary and immortalized esophageal epithelial cell lines in response to its synthetic ligand polyinosinic polycytidylic acid [poly(I:C)]. Through reporter gene studies, we show that poly(I:C)-induced NF-kappaB activation is critical for the transactivation of the IL-8 promoter in vitro and that nuclear translocation of NF-kappaB occurs at an early time point following poly(I:C) stimulation of esophageal epithelial cells. Importantly, we also show that poly(I:C) stimulation induces the NF-kappaB-dependent esophageal epithelial expression of TLR2, leading to enhanced epithelial responsiveness of EPC2-hTERT cells to TLR2 ligand stimulation, suggesting an important regulatory role for TLR3-mediated NF-kappaB signaling in the innate immune response of esophageal epithelial cells. Our findings demonstrate for the first time that TLR3 is highly functional in the human esophageal epithelium and that TLR3-mediated NF-kappaB signaling may play an important regulatory role in esophageal epithelial homeostasis.

  16. Quantitation of IgG kappa and IgG lambda in the cerebrospinal fluid by sandwich ELISA method.

    PubMed

    Zeman, David; Kušnierová, Pavlína; Bojková, Jana; Všianský, František; Zapletalová, Olga

    2017-01-01

    IgG kappa and IgG lambda concentrations were quantified in 96 paired CSF and sera using Hevylite™ antibodies in an in-house developed sandwich ELISA method. In 56 of these samples, the results were compared with a qualitative isoelectric focusing/affinity-mediated immunoblotting assay for oligoclonal IgG kappa and IgG lambda. Normal IgG kappa/lambda ratio in the CSF was the same as in serum. In 19/33 patients with intrathecal oligoclonal IgG synthesis, skewed IgG kappa/lambda ratio was observed (increased in 16 and decreased in 3 cases). The analysis of light chain composition of intrathecally synthesised immunoglobulins could contribute to our understanding of intrathecal humoral immune response, although its diagnostic utility is limited.

  17. Quiet-Time Suprathermal ( 0.1-1.5 keV) Electrons in the Solar Wind

    NASA Astrophysics Data System (ADS)

    Wang, L.; Tao, J.; Zong, Q.; Li, G.; Salem, C. S.; Wimmer-Schweingruber, R. F.; He, J.; Tu, C.; Bale, S. D.

    2016-12-01

    We present a statistical survey of the energy spectrum of solar wind suprathermal (˜0.1-1.5 keV) electrons measured by the WIND/3DP instrument at 1 AU during quiet times at the minimum and maximum of solar cycles 23 and 24. After separating (beaming) strahl electrons from (isotropic) halo electrons according to their different behaviors in the angular distribution, we fit the observed energy spectrum of both strahl and halo electrons at ˜0.1-1.5 keV to a Kappa distribution function with an index κ and effective temperature Teff. We also calculate the number density n and average energy Eavg of strahl and halo electrons by integrating the electron measurements between ˜0.1 and 1.5 keV. We find a strong positive correlation between κ and Teff for both strahl and halo electrons, and a strong positive correlation between the strahl n and halo n, likely reflecting the nature of the generation of these suprathermal electrons. In both solar cycles, κ is larger at solar minimum than at solar maximum for both strahl and halo electrons. The halo κ is generally smaller than the strahl κ (except during the solar minimum of cycle 23). The strahl n is larger at solar maximum, but the halo n shows no difference between solar minimum and maximum. Both the strahl n and halo n have no clear association with the solar wind core population, but the density ratio between the strahl and halo roughly anti-correlates (correlates) with the solar wind density (velocity).

  18. Quiet-time Suprathermal (~0.1-1.5 keV) Electrons in the Solar Wind

    NASA Astrophysics Data System (ADS)

    Tao, Jiawei; Wang, Linghua; Zong, Qiugang; Li, Gang; Salem, Chadi S.; Wimmer-Schweingruber, Robert F.; He, Jiansen; Tu, Chuanyi; Bale, Stuart D.

    2016-03-01

    We present a statistical survey of the energy spectrum of solar wind suprathermal (˜0.1-1.5 keV) electrons measured by the WIND 3DP instrument at 1 AU during quiet times at the minimum and maximum of solar cycles 23 and 24. After separating (beaming) strahl electrons from (isotropic) halo electrons according to their different behaviors in the angular distribution, we fit the observed energy spectrum of both strahl and halo electrons at ˜0.1-1.5 keV to a Kappa distribution function with an index κ and effective temperature Teff. We also calculate the number density n and average energy Eavg of strahl and halo electrons by integrating the electron measurements between ˜0.1 and 1.5 keV. We find a strong positive correlation between κ and Teff for both strahl and halo electrons, and a strong positive correlation between the strahl n and halo n, likely reflecting the nature of the generation of these suprathermal electrons. In both solar cycles, κ is larger at solar minimum than at solar maximum for both strahl and halo electrons. The halo κ is generally smaller than the strahl κ (except during the solar minimum of cycle 23). The strahl n is larger at solar maximum, but the halo n shows no difference between solar minimum and maximum. Both the strahl n and halo n have no clear association with the solar wind core population, but the density ratio between the strahl and halo roughly anti-correlates (correlates) with the solar wind density (velocity).

  19. Electron beam machining using rotating and shaped beam power distribution

    DOEpatents

    Elmer, J.W.; O`Brien, D.W.

    1996-07-09

    An apparatus and method are disclosed for electron beam (EB) machining (drilling, cutting and welding) that uses conventional EB guns, power supplies, and welding machine technology without the need for fast bias pulsing technology. The invention involves a magnetic lensing (EB optics) system and electronic controls to: (1) concurrently bend, focus, shape, scan, and rotate the beam to protect the EB gun and to create a desired effective power-density distribution, and (2) rotate or scan this shaped beam in a controlled way. The shaped beam power-density distribution can be measured using a tomographic imaging system. For example, the EB apparatus of this invention has the ability to drill holes in metal having a diameter up to 1,000 {micro}m (1 mm or larger), compared to the 250 {micro}m diameter of laser drilling. 5 figs.

  20. Corneal NF-kappaB activity is necessary for the retention of transparency in the cornea of UV-B-exposed transgenic reporter mice.

    PubMed

    Alexander, George; Carlsen, Harald; Blomhoff, Rune

    2006-04-01

    To determine the dynamics of Nuclear Factor-kappaB (NF-kappaB) in murine corneal pathology and the role of NF-kappaB in maintaining corneal clarity after ultraviolet B radiation insult, transgenic mice containing NF-kappaB-luciferase reporter were exposed to LPS (bacterial lipopolysaccharide), TNF-alpha (Tumor Necrosis Factor-alpha) or 4 kJ m(-2) UV-B radiation. NF-kappaB decoy oligonucleotides were also administered in some of the UV-B experiments. Following various exposure times, the mice were sacrificed and whole eyes or corneal tissues were obtained. Whole eyes were examined for scattering using a point-source optical imaging technique. Tissue homogenates were examined for luciferase activity using a luminometer. TNF-alpha and LPS-injected NF-kappaB-luciferase transgenic mice demonstrated 3-10-fold increases in cornea NF-kappaB with peak activities at 4 and 6 hr post-injection, respectively. Mice exposed to 4 kJ m(-2) UV-B exhibited a 3-fold increase in NF-kappaB activity 4 hr post-exposure. The administration of NF-kappaB-decoy oligonucleotides to mice had the effect of reducing UV-B-induced NF-kappaB activity in the cornea and significantly increasing the amount of light scattering in UV-B exposed corneas 7 days post-UV-B exposure when compared to sham injected mice. These results indicate that NF-kappaB is activated in cornea in pathologies that involves increased plasma levels of LPS and TNF-alpha, as well as direct UV-B exposure, and suggest that NF-kappaB activation play an essential part in the corneal healing process.

  1. T cell-intrinsic requirement for NF-kappa B induction in postdifferentiation IFN-gamma production and clonal expansion in a Th1 response.

    PubMed

    Corn, Radiah A; Aronica, Mark A; Zhang, Fuping; Tong, Yingkai; Stanley, Sarah A; Kim, Se Ryoung Agnes; Stephenson, Linda; Enerson, Ben; McCarthy, Susan; Mora, Ana; Boothby, Mark

    2003-08-15

    NF-kappaB/Rel transcription factors are linked to innate immune responses and APC activation. Whether and how the induction of NF-kappaB signaling in normal CD4(+) T cells regulates effector function are not well-understood. The liberation of NF-kappaB dimers from inhibitors of kappaB (IkappaBs) constitutes a central checkpoint for physiologic regulation of most forms of NF-kappaB. To investigate the role of NF-kappaB induction in effector T cell responses, we targeted inhibition of the NF-kappaB/Rel pathway specifically to T cells. The Th1 response in vivo is dramatically weakened when T cells defective in their NF-kappaB induction (referred to as IkappaBalpha(DeltaN) transgenic cells) are activated by a normal APC population. Analyses in vivo, and IL-12-supplemented T cell cultures in vitro, reveal that the mechanism underlying this T cell-intrinsic requirement for NF-kappaB involves activation of the IFN-gamma gene in addition to clonal expansion efficiency. The role of NF-kappaB in IFN-gamma gene expression includes a modest decrease in Stat4 activation, T box expressed in T cell levels, and differentiation efficiency along with a more prominent postdifferentiation step. Further, induced expression of Bcl-3, a trans-activating IkappaB-like protein, is decreased in T cells as a consequence of NF-kappaB inhibition. Together, these findings indicate that NF-kappaB induction in T cells regulates efficient clonal expansion, Th1 differentiation, and IFN-gamma production by Th1 lymphocytes at a control point downstream from differentiation.

  2. 78 FR 46621 - Status of the Office of New Reactors' Implementation of Electronic Distribution of Advanced...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-01

    ... of Electronic Distribution of Advanced Reactor Correspondence AGENCY: Nuclear Regulatory Commission. ACTION: Implementation of electronic distribution of advanced reactor correspondence; issuance. SUMMARY... public that, in the future, publicly available correspondence originating from the Division of Advanced...

  3. Lymphotoxin activation by human T-cell leukemia virus type I-infected cell lines: role for NF-kappa B.

    PubMed

    Paul, N L; Lenardo, M J; Novak, K D; Sarr, T; Tang, W L; Ruddle, N H

    1990-11-01

    Human T-cell leukemia virus type I (HTLV-I)-infected T-cell lines constitutively produce high levels of biologically active lymphotoxin (LT; tumor necrosis factor-beta) protein and LT mRNA. To understand the regulation of LT transcription by HTLV-I, we analyzed the ability of a series of deletions of the LT promoter to drive the chloramphenicol acetyltransferase (CAT) reporter gene in HTLV-I-positive MT-2 cells. The smallest LT promoter fragment (-140 to +77) that was able to drive CAT activity contained a site that was similar to the immunoglobulin kappa-chain NF-kappa B-binding site. Since the HTLV-I tax gene activates the nuclear form of NF-kappa B, this finding suggested a possible means of HTLV-I activation of LT production. We found that the LT kappa B-like site specifically formed a complex with NF-kappa B-containing nuclear extract from MT-2, C81-66-45, and other activated T cells. Mutation of the LT kappa B site in the context of the LT promoter (-293 to +77) (mutant M1) reduced the ability of the promoter to drive the CAT gene in HTLV-I-infected and noninfected human T-cell lines. These data suggest a general role for NF-kappa B activation in the induction of LT gene transcription. Activation of LT in HTLV-I-infected cells may explain the pathology associated with HTLV-I infection, including the hypercalcemia that is prevalent in adult T-cell leukemia.

  4. Reactive oxygen species mediate liver injury through parenchymal nuclear factor-kappaB inactivation in prolonged ischemia/reperfusion.

    PubMed

    Llacuna, Laura; Marí, Montserrat; Lluis, Josep M; García-Ruiz, Carmen; Fernández-Checa, José C; Morales, Albert

    2009-05-01

    Nuclear factor (NF)-kappaB participates in ischemia/reperfusion (I/R) hepatic signaling, stimulating both protective mechanisms and the generation of inflammatory cytokines. After analyzing NF-kappaB activation during increasing times of ischemia in murine I/R, we observed that the nuclear translocation of p65 paralleled Src and IkappaB tyrosine phosphorylation, which peaked after 60 minutes of ischemia. After extended ischemic periods (90 to 120 minutes) however, nuclear p65 levels were inversely correlated with the progressive induction of oxidative stress. Despite this profile of NF-kappaB activation, inflammatory genes, such as tumor necrosis factor (TNF) and interleukin (IL)-1beta, predominantly induced by Kupffer cells, increased throughout time during ischemia (30 to 120 minutes), whereas protective NF-kappaB-dependent genes, such as manganese superoxide dismutase (Mn-SOD), expressed in parenchymal cells, decreased. Consistent with this behavior, gadolinium chloride pretreatment abolished TNF/IL-1beta up-regulation during ischemia without affecting Mn-SOD levels. Interestingly, specific glutathione (GSH) up-regulation in hepatocytes by S-adenosylmethionine increased Mn-SOD expression and protected against I/R-mediated liver injury despite TNF/IL-1beta induction. Similar protection was achieved by administration of the SOD mimetic MnTBAP. In contrast, indiscriminate hepatic GSH depletion by buthionine-sulfoximine before I/R potentiated oxidative stress and decreased both nuclear p65 and Mn-SOD expression levels, increasing TNF/IL-1beta up-regulation and I/R-induced liver damage. Thus, the divergent role of NF-kappaB activation in selective liver cell populations underlies the dichotomy of NF-kappaB in hepatic I/R injury, illustrating the relevance of specifically maintaining NF-kappaB activation in parenchymal cells.

  5. p38 mitogen-activated protein kinase up-regulates NF-{kappa}B transcriptional activation through RelA phosphorylation during stretch-induced myogenesis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ji, Guoping; Liu, Dongxu; Liu, Jing

    2010-01-01

    p38 MAPK and nuclear factor-B (NF-B) signaling pathways play an indispensable role in the control of skeletal myogenesis. The specific contribution of these signaling pathways to the response of myoblast to the mechanical stimulation and the molecular mechanisms underlying this response remain unresolved. Using an established in vitro model, we now show that p38 MAP kinase activity regulates the transcriptional activation of NF-{kappa}B in response to mechanical stimulation of myoblasts. Furthermore, SB203580 blocked stretch-induced NF-{kappa}B activation during myogenesis, not through down-regulation of degradation of I{kappa}B-{alpha}, and consequent translocation of the p65 subunit of NF-{kappa}B to the nucleus. It is likelymore » that stretch-induced NF-{kappa}B activation by phosphorylation of p65 NF-{kappa}B. Moreover, depletion of p38{alpha} using siRNA significantly reduces stretch-induced phosphorylation of RelA and NF-{kappa}B activity. These results provides the first evidence of a cross-talk between p38 MAPK and NF-{kappa}B signaling pathways during stretch-induced myogenesis, with phosphorylation of RelA being one of the effectors of this promyogenic mechanism. The {alpha} isoform of p38MAP kinase regulates the transcriptional activation of NF-{kappa}B following stimulation with cyclic stretch.« less

  6. NF-kappaB signaling blockade by Bay 11-7085 during early cardiac morphogenesis induces alterations of the outflow tract in chicken heart.

    PubMed

    Hernández-Gutierrez, S; García-Peláez, I; Zentella-Dehesa, A; Ramos-Kuri, M; Hernández-Franco, P; Hernández-Sánchez, F; Rojas, E

    2006-07-01

    Nuclear factor kappaB (NF-kappaB) is a pleiotropic transcription factor implicated in the regulation of diverse morphologic cardiac alterations, for which the p50 and p65 subunits form the most prevalent dimeric form in the heart. NF-kappaB is inactivated by proteins of the IkappaB family, which trap it in the cytoplasm. It is not known whether NF-kappaB influences cardiac development. Here we investigated the role of NF-kappaB in regulating transcription in chicken heart morphogenesis. Specifically, we tested whether NF-kappaB activation is required for normal formation of the outflow tract (OFT) during a critical stage of heart development. We designed a reporter vector with kappaB binding sites for Rel family members in the promoter, upstream from the cDNA of Green Fluorescent Protein (GFP). This construct was injected directly into the developing heart of chicken embryos. NF-kappaB activation was subsequently inhibited by administration of the specific pharmacological agent Bay 11-7085. We found that forced NF-kappaB expression was associated with multiple congenital cardiac alterations of the OFT (mainly IVC, DORV and great arteries stenosis). These findings indicate that blockade of NF-kappaB induces apoptosis and is an important factor in the development of OFT during cardiogenesis. However, it remains unknown which members of the Rel family are relevant in this process.

  7. Activation of kappa opioid receptors in the dorsal raphe have sex dependent effects on social behavior in California mice.

    PubMed

    Wright, Emily C; Parks, Tiffany V; Alexander, Jonathon O; Supra, Rajesh; Trainor, Brian C

    2018-06-06

    Kappa opioid receptor activation has been linked to stress and anxiety behavior, thus leading to kappa antagonists being popularized in research as potential anxiolytics. However, while these findings may hold true in standard models, the neuromodulatory effects of social defeat may change the behavioral outcome of kappa opioid receptor activation. Previous research has shown that social defeat can lead to hyperactivity of serotonergic neurons in the dorsal raphe nucleus, and that inhibition of this increase blocks the social deficits caused by defeat. Kappa opioid receptor activation in the dorsal raphe nucleus works to decrease serotonergic activity. We injected the kappa opioid receptor U50,488 directly into the dorsal raphe nucleus of male and female, defeat and control adult California mice. Here we show evidence that U50,488 induces anxiety behavior in control male California mice, but helps relieve it in defeated males. Consistent with previous literature, we find little effect in females adding evidence that there are marked and important sex differences in the kappa opioid system. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Study of electron beam on electron cyclotron waves with AC field in the magnetosphere of Uranus

    NASA Astrophysics Data System (ADS)

    Kaur, Rajbir; Kumari, Jyoti; Pandey, R. S.

    2018-05-01

    In this paper, we deal with the oblique electromagnetic electron cyclotron (EMEC) waves in the Uranus magnetosphere. The expression of the dispersion relation is plotted by using the method of the feature solution. After the kinetic method, the growth rate and the actual frequency of the EMEC wave are studied theoretically in the Uranian system. NASA, Voyager 2, the observed results of the space detectors show that the spin axes of the planets are abnormally oriented and that there are more particles in the high energy tail of the Uranian magnetospheric plasma. Therefore, this paper uses the Kappa distribution instead of the usual Maxwell distribution. The study extends to the tilt propagation of EMEC waves, which has a change in temperature anisotropy and propagation angle with respect to the direction of the magnetic field. These parameters were found to support the growth rate of EMEC waves. However, the response of the actual frequency of these waves is not the same as the rate of growth in all cases. These results apply to the detailed comparison of planetary studies of the space plasma environment and the magnetosphere system.

  9. Plant extracts from stinging nettle (Urtica dioica), an antirheumatic remedy, inhibit the proinflammatory transcription factor NF-kappaB.

    PubMed

    Riehemann, K; Behnke, B; Schulze-Osthoff, K

    1999-01-08

    Activation of transcription factor NF-kappaB is elevated in several chronic inflammatory diseases and is responsible for the enhanced expression of many proinflammatory gene products. Extracts from leaves of stinging nettle (Urtica dioica) are used as antiinflammatory remedies in rheumatoid arthritis. Standardized preparations of these extracts (IDS23) suppress cytokine production, but their mode of action remains unclear. Here we demonstrate that treatment of different cells with IDS23 potently inhibits NF-kappaB activation. An inhibitory effect was observed in response to several stimuli, suggesting that IDS23 suppressed a common NF-kappaB pathway. Inhibition of NF-kappaB activation by IDS23 was not mediated by a direct modification of DNA binding, but rather by preventing degradation of its inhibitory subunit IkappaB-alpha. Our results suggests that part of the antiinflammatory effect of Urtica extract may be ascribed to its inhibitory effect on NF-kappaB activation.

  10. Electron flat-top distributions and cross-scale wave modulations observed in the current sheet of geomagnetic tail

    NASA Astrophysics Data System (ADS)

    Zhao, Duo; Fu, Suiyan; Parks, George K.; Sun, Weijie; Zong, Qiugang; Pan, Dongxiao; Wu, Tong

    2017-08-01

    We present new observations of electron distributions and the accompanying waves during the current sheet activities at ˜60 RE in the geomagnetic tail detected by the ARTEMIS (Acceleration, Reconnection, Turbulence, and Electrodynamics of the Moon's Interaction with the Sun) spacecraft. We find that electron flat-top distribution is a common feature near the neutral sheet of the tailward flowing plasmas, consistent with the electron distributions that are shaped in the reconnection region. Whistler mode waves are generated by the anisotropic electron temperature associated with the electron flat-top distributions. These whistler mode waves are modulated by low frequency ion scale waves that are possibly excited by the high-energy ions injected during the current sheet instability. The magnetic and electric fields of the ion scale waves are in phase with electron density variations, indicating that they are compressional ion cyclotron waves. Our observations present examples of the dynamical processes occurring during the current sheet activities far downstream of the geomagnetic tail.

  11. Calculations of the Electron Energy Distribution Function in a Uranium Plasma by Analytic and Monte Carlo Techniques. Ph.D. Thesis

    NASA Technical Reports Server (NTRS)

    Bathke, C. G.

    1976-01-01

    Electron energy distribution functions were calculated in a U235 plasma at 1 atmosphere for various plasma temperatures and neutron fluxes. The distributions are assumed to be a summation of a high energy tail and a Maxwellian distribution. The sources of energetic electrons considered are the fission-fragment induced ionization of uranium and the electron induced ionization of uranium. The calculation of the high energy tail is reduced to an electron slowing down calculation, from the most energetic source to the energy where the electron is assumed to be incorporated into the Maxwellian distribution. The pertinent collisional processes are electron-electron scattering and electron induced ionization and excitation of uranium. Two distinct methods were employed in the calculation of the distributions. One method is based upon the assumption of continuous slowing and yields a distribution inversely proportional to the stopping power. An iteration scheme is utilized to include the secondary electron avalanche. In the other method, a governing equation is derived without assuming continuous electron slowing. This equation is solved by a Monte Carlo technique.

  12. NIK and Cot cooperate to trigger NF-kappaB p65 phosphorylation.

    PubMed

    Wittwer, Tobias; Schmitz, M Lienhard

    2008-06-27

    The serine/threonine kinase Cot triggers NF-kappaB-dependent transactivation and activation of various MAPKinases. Here we identify Cot as a novel p65 interacting protein kinase. Cot expression induces p65 phosphorylation at serines 536 and 468 in dependence from its kinase function. Accordingly, shRNA-mediated knockdown of Cot expression interferes with TNF-induced NF-kappaB-dependent gene expression. Also the C-terminally truncated, oncogenic form of Cot is able to trigger p65 phosphorylation. In vitro kinase assays and dominant negative mutants revealed that NIK functions downstream of Cot to mediate p65 phosphorylation.

  13. Novel selective kappa-opioid ligands.

    PubMed

    Peeters, O M; Jamroz, D; Blaton, N M; De Ranter, C J

    1999-03-15

    The single-crystal X-ray structures of (-)-dimethyl[(2S)-1-(5,6,7,8- tetrahydro-5-oxonaphthalene-2-acetyl)piperidin-2-ylmethyl ]ammonium chloride, C20H29N2O2+.Cl-(BRL-53001A), and (-)-ethylmethyl[(2S)-1-(5,6,7,8-tetrahydro-5-oxonaphthalene- 2- acetyl)piperidin-2-ylmethyl]-ammonium chloride dihydrate, C21H31N2O2+.Cl-.2H2O (BRL-53188A), have been determined. The two molecules have different conformations in the 1-tetralon-6-ylacetyl residue but the same conformation in the 1-acetyl-2-(dialkylaminomethyl)piperidine moiety. The conformations found are in agreement with the required chemical features for kappa affinity and antinociceptive potency.

  14. Clock distribution for BaF2 readout electronics at CSNS-WNS

    NASA Astrophysics Data System (ADS)

    He, Bing; Cao, Ping; Zhang, De-Liang; Wang, Qi; Zhang, Ya-Xi; Qi, Xin-Cheng; An, Qi

    2017-01-01

    A BaF2 (Barium Fluoride) detector array is designed to precisely measure the (n, γ) cross section at the CSNS-WNS (white neutron source at China Spallation Neutron Source). It is a 4π solid angle-shaped detector array consisting of 92 BaF2 crystal elements. To discriminate signals from the BaF2 detector, a pulse shape discrimination method is used, supported by a waveform digitization technique. There are 92 channels for digitizing. The precision and synchronization of clock distribution restricts the performance of waveform digitizing. In this paper, a clock prototype for the BaF2 readout electronics at CSNS-WNS is introduced. It is based on the PXIe platform and has a twin-stage tree topology. In the first stage, clock is synchronously distributed from the tree root to each PXIe crate through a coaxial cable over a long distance, while in the second stage, the clock is further distributed to each electronic module through a PXIe dedicated differential star bus. With the help of this topology, each tree node can fan out up to 20 clocks with 3U size. Test results show the clock jitter is less than 20 ps, which meets the requirements of the BaF2 readout electronics. Besides, this clock system has the advantages of high density, simplicity, scalability and cost saving, so it can be useful for other clock distribution applications. Supported by National Research and Development plan (2016 YFA0401602) NSAF (U1530111) and National Natural Science Foundation of China (11005107)

  15. NBBA, a synthetic small molecule, inhibits TNF-{alpha}-induced angiogenesis by suppressing the NF-{kappa}B signaling pathway

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kim, Nam Hee; Jung, Hye Jin; Shibasaki, Futoshi

    2010-01-15

    Nuclear factor-{kappa}B (NF-{kappa}B) is a crucial transcription factor that contributes to cancer development by regulating a number of genes involved in angiogenesis and tumorigenesis. Here, we describe (Z)-N-(3-(7-nitro-3-oxobenzo[d][1,2]selenazol-2(3H)-yl)benzylidene) propan-2-amine oxide (NBBA) as a new anti-angiogenic small molecule that targets NF-{kappa}B activity. NBBA showed stronger growth inhibition on human umbilical vein endothelial cells (HUVECs) than on the cancer cell lines we tested. Moreover, NBBA inhibited tumor necrosis factor-alpha (TNF-{alpha})-induced tube formation and invasion of HUVECs. In addition, NBBA suppressed the neovascularization of chorioallantonic membrane from growing chick embryos in vivo. To address the mode of action of the compound, the effectmore » of NBBA on TNF-{alpha}-induced NF-{kappa}B transcription activity was investigated. NBBA suppressed TNF-{alpha}-induced c-Jun N-terminal kinase phosphorylation, which resulted in suppression of transcription of NF-{kappa}B and its target genes, including interleukin-8, interleukin-1{alpha}, and epidermal growth factor. Collectively, these results demonstrated that NBBA is a new anti-angiogenic small molecule that targets the NF-{kappa}B signaling pathway.« less

  16. Thalidomide suppresses NF-kappa B activation induced by TNF and H2O2, but not that activated by ceramide, lipopolysaccharides, or phorbol ester.

    PubMed

    Majumdar, Sekhar; Lamothe, Betty; Aggarwal, Bharat B

    2002-03-15

    Thalidomide ([+]-alpha-phthalimidoglutarimide), a psychoactive drug that readily crosses the blood-brain barrier, has been shown to exhibit anti-inflammatory, antiangiogenic, and immunosuppressive properties through a mechanism that is not fully established. Due to the central role of NF-kappaB in these responses, we postulated that thalidomide mediates its effects through suppression of NF-kappaB activation. We investigated the effects of thalidomide on NF-kappaB activation induced by various inflammatory agents in Jurkat cells. The treatment of these cells with thalidomide suppressed TNF-induced NF-kappaB activation, with optimum effect occurring at 50 microg/ml thalidomide. These effects were not restricted to T cells, as other hematopoietic and epithelial cell types were also inhibited. Thalidomide suppressed H(2)O(2)-induced NF-kappaB activation but had no effect on NF-kappaB activation induced by PMA, LPS, okadaic acid, or ceramide, suggesting selectivity in suppression of NF-kappaB. The suppression of TNF-induced NF-kappaB activation by thalidomide correlated with partial inhibition of TNF-induced degradation of an inhibitory subunit of NF-kappaB (IkappaBalpha), abrogation of IkappaBalpha kinase activation, and inhibition of NF-kappaB-dependent reporter gene expression. Thalidomide abolished the NF-kappaB-dependent reporter gene expression activated by overexpression of TNFR1, TNFR-associated factor-2, and NF-kappaB-inducing kinase, but not that activated by the p65 subunit of NF-kappaB. Overall, our results clearly demonstrate that thalidomide suppresses NF-kappaB activation specifically induced by TNF and H(2)O(2) and that this may contribute to its role in suppression of proliferation, inflammation, angiogenesis, and the immune system.

  17. Kappa and Hirschberg ratio measured with an automated video gaze tracker.

    PubMed

    Schaeffel, Frank

    2002-05-01

    To develop a fast automated procedure to measure kappa and the Hirschberg ratio for immediate use in a video gaze tracker. Using the hardware platform of the PowerRefractor and a 200 mm lens, the pupil was imaged with a resolution of 57 pixels/mm, at a camera distance of 90 cm. Both the positions of the first Purkinje image and the edges of the pupil were located at 25 Hz sampling rate with subpixel resolution using video image processing software developed under Borland C++. Subjects fixated on a red spot on the left side of the monitor. If their fixation was stable (standard deviation <0.2 degrees in 25 subsequent measurements evaluated in 1 s), the fixation spot appeared automatically on the right side, and the procedure was repeated. Data on the angular position of the optical axis for both targets were stored and provided kappa and the Hirschberg ratio with a standard deviation of about 0.2 degrees or better. This enabled the system to track fixation with a resolution of about 0.2 degrees. (1) Kappa was +3.91+/-2.73 degrees (right eyes), -3.93+/-2.68 degrees (left eyes, mean +/- SD from 24 young adults). Kappa was highly correlated in both eyes (r = 0.8996), but there were significant asymmetries between both eyes in three subjects (delta up to 3 degrees). (2) The Hirschberg ratios were 12.93+/-1.23 degrees/mm = 22.56 delta/mm (right eyes) and 12.82+/-1.49 degrees/mm = 22.38 delta/mm (left eyes). They were also highly correlated in both eyes (r = 0.931). (3) Neither kappa nor the Hirschberg ratios were correlated to refractive errors (range +0.50 to -7.75 D, mean -1.73+/-2.29 D [spherical equivalents]). (1) The video gaze tracker measured fixation with an angular resolution high enough to display the eye position during reading of individual words on the computer screen. (2) The applicable Hirschberg ratio changed with the power of the spectacles of the subjects by about 3% per diopter. (3) In some subjects, there were significant differences in the geometry

  18. The kappa Distribution as Tool in Investigating Hot Plasmas in the Magnetospheres of Outer Planets

    NASA Astrophysics Data System (ADS)

    Krimigis, S. M.; Carbary, J. F.

    2014-12-01

    The first use of a Maxwellian distribution with a high-energy tail (a κ-function) was made by Olbert (1968) and applied by Vasyliunas (1968) in analyzing electron data. The k-function combines aspects of both Maxwellian and power law forms to provide a reasonably complete description of particle density, temperature, pressure and convection velocity, all of which are key parameters of magnetospheric physics. Krimigis et al (1979) used it to describe flowing plasma ions in Jupiter's magnetosphere measured by Voyager 1, and obtained temperatures in the range of 20 to 35 keV. Sarris et al (1981) used the κ-function to describe plasmas in Earth's distant plasma sheet. The κ-function, in various formulations and names (e. g., γ-thermal distribution, Krimigis and Roelof, 1983) has been used routinely to parametrize hot, flowing plasmas in the magnetospheres of the outer planets, with typical kT ~ 10 to 50 keV. Using angular measurements, it has been possible to obtain pitch angle distributions and convective flow directions in sufficient detail for computations of temperatures and densities of hot particle pressures. These 'hot' pressures typically dominate the cold plasma pressures in the high beta (β > 1) magnetospheres of Jupiter and Saturn, but are of less importance in the relatively empty (β < 1) magnetospheres of Uranus and Neptune. Thus, the κ-function represents an effective tool in analyzing plasma behavior in planetary magnetospheres, but it is not applicable in all plasma environments. References Olbert, S., in Physics of the Magnetosphere, (Carovillano, McClay, Radoski, Eds), Springer-Verlag, New York, p. 641-659, 1968 Vasyliunas, V., J. Geophys. Res., 73(9), 2839-2884, 1968 Krimigis, S. M., et al, Science 204, 998-1003, 1979 Sarris, E., et al, Geophys. Res. Lett. 8, 349-352, 1981 Krimigis, S. M., and E. C. Roelof, Physics of the Jovian Magnetosphere, edited by A. J. Dessler, 106-156, Cambridge University Press, New York, 1983

  19. Lymphotoxin activation by human T-cell leukemia virus type I-infected cell lines: role for NF-kappa B.

    PubMed Central

    Paul, N L; Lenardo, M J; Novak, K D; Sarr, T; Tang, W L; Ruddle, N H

    1990-01-01

    Human T-cell leukemia virus type I (HTLV-I)-infected T-cell lines constitutively produce high levels of biologically active lymphotoxin (LT; tumor necrosis factor-beta) protein and LT mRNA. To understand the regulation of LT transcription by HTLV-I, we analyzed the ability of a series of deletions of the LT promoter to drive the chloramphenicol acetyltransferase (CAT) reporter gene in HTLV-I-positive MT-2 cells. The smallest LT promoter fragment (-140 to +77) that was able to drive CAT activity contained a site that was similar to the immunoglobulin kappa-chain NF-kappa B-binding site. Since the HTLV-I tax gene activates the nuclear form of NF-kappa B, this finding suggested a possible means of HTLV-I activation of LT production. We found that the LT kappa B-like site specifically formed a complex with NF-kappa B-containing nuclear extract from MT-2, C81-66-45, and other activated T cells. Mutation of the LT kappa B site in the context of the LT promoter (-293 to +77) (mutant M1) reduced the ability of the promoter to drive the CAT gene in HTLV-I-infected and noninfected human T-cell lines. These data suggest a general role for NF-kappa B activation in the induction of LT gene transcription. Activation of LT in HTLV-I-infected cells may explain the pathology associated with HTLV-I infection, including the hypercalcemia that is prevalent in adult T-cell leukemia. Images PMID:1976820

  20. Baicalin attenuates focal cerebral ischemic reperfusion injury through inhibition of nuclear factor {kappa}B p65 activation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Xue, Xia; Center for New Drugs Evaluation, Shandong University, Jinan 250012; Qu, Xian-Jun

    Research highlights: {yields} Permanent NF-{kappa}B p65 activation contributes to the infarction after ischemia-reperfusion injury in rats. {yields} Baicalin can markedly inhibit the nuclear NF-{kappa}B p65 expression and m RNA levels after ischemia-reperfusion injury in rats. {yields} Baicalin decreased the cerebral infarction area via inhibiting the activation of nuclear NF-{kappa}B p65. -- Abstract: Baicalin is a flavonoid compound purified from plant Scutellaria baicalensis Georgi. We aimed to evaluate the neuroprotective effects of baicalin against cerebral ischemic reperfusion injury. Male Wistar rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion for 24 h. Baicalin at dosesmore » of 50, 100 and 200 mg/kg was intravenously injected after ischemia onset. Twenty-four hours after reperfusion, the neurological deficit was scored and infarct volume was measured. Hematoxylin and eosin (HE) staining was performed to analyze the histopathological changes of cortex and hippocampus neurons. We examined the levels of NF-{kappa}B p65 in ischemic cortexes by Western blot analysis and RT-PCR assay. The results showed that the neurological deficit scores were significantly decreased from 2.0 {+-} 0.7 to 1.2 {+-} 0.4 and the volume of infarction was reduced by 25% after baicalin injection. Histopathological examination showed that the increase of neurons with pycnotic shape and condensed nuclear in cortex and hippocampus were not observed in baicalin treated animals. Further examination showed that NF-{kappa}B p65 in cortex was increased after ischemia reperfusion injury, indicating the molecular mechanism of ischemia reperfusion injury. The level of NF-{kappa}B p65 was decreased by 73% after baicalin treatment. These results suggest that baicalin might be useful as a potential neuroprotective agent in stroke therapy. The neuroprotective effects of baicalin may relate to inhibition of NF-{kappa}B p65.« less

  1. Probe measurements of the electron velocity distribution function in beams: Low-voltage beam discharge in helium

    NASA Astrophysics Data System (ADS)

    Sukhomlinov, V.; Mustafaev, A.; Timofeev, N.

    2018-04-01

    Previously developed methods based on the single-sided probe technique are altered and applied to measure the anisotropic angular spread and narrow energy distribution functions of charged particle (electron and ion) beams. The conventional method is not suitable for some configurations, such as low-voltage beam discharges, electron beams accelerated in near-wall and near-electrode layers, and vacuum electron beam sources. To determine the range of applicability of the proposed method, simple algebraic relationships between the charged particle energies and their angular distribution are obtained. The method is verified for the case of the collisionless mode of a low-voltage He beam discharge, where the traditional method for finding the electron distribution function with the help of a Legendre polynomial expansion is not applicable. This leads to the development of a physical model of the formation of the electron distribution function in a collisionless low-voltage He beam discharge. The results of a numerical calculation based on Monte Carlo simulations are in good agreement with the experimental data obtained using the new method.

  2. Incensole acetate, a novel anti-inflammatory compound isolated from Boswellia resin, inhibits nuclear factor-kappa B activation.

    PubMed

    Moussaieff, Arieh; Shohami, Esther; Kashman, Yoel; Fride, Ester; Schmitz, M Lienhard; Renner, Florian; Fiebich, Bernd L; Munoz, Eduardo; Ben-Neriah, Yinon; Mechoulam, Raphael

    2007-12-01

    Boswellia resin is a major anti-inflammatory agent in herbal medical tradition, as well as a common food supplement. Its anti-inflammatory activity has been attributed to boswellic acid and its derivatives. Here, we re-examined the anti-inflammatory effect of the resin, using inhibitor of nuclear factor-kappaB alpha (IkappaB alpha) degradation in tumor necrosis factor (TNF) alpha-stimulated HeLa cells for a bioassay-guided fractionation. We thus isolated two novel nuclear factor-kappaB (NF-kappaB) inhibitors from the resin, their structures elucidated as incensole acetate (IA) and its nonacetylated form, incensole (IN). IA inhibited TAK/TAB-mediated IkappaB kinase (IKK) activation loop phosphorylation, resulting in the inhibition of cytokine and lipopolysaccharide-mediated NF-kappaB activation. It had no effect on IKK activity in vitro, and it did not suppress IkappaB alpha phosphorylation in costimulated T-cells, indicating that the kinase inhibition is neither direct nor does it affect all NF-kappaB activation pathways. The inhibitory effect seems specific; IA did not interfere with TNFalpha-induced activation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase. IA treatment had a robust anti-inflammatory effect in a mouse inflamed paw model. Cembrenoid diterpenoids, specifically IA and its derivatives, may thus constitute a potential novel group of NF-kappaB inhibitors, originating from an ancient anti-inflammatory herbal remedy.

  3. Turbulent Equilibria for Charged Particles in Space

    NASA Astrophysics Data System (ADS)

    Yoon, Peter

    2017-04-01

    The solar wind electron distribution function is apparently composed of several components including non-thermal tail population. The electron distribution that contains energetic tail feature is well fitted with the kappa distribution function. The solar wind protons also possess quasi power-law tail distribution function that is well fitted with an inverse power law model. The present paper discusses the latest theoretical development regarding the dynamical steady-state solution of electrons and Langmuir turbulence that are in turbulent equilibrium. According to such a theory, the Maxwellian and kappa distribution functions for the electrons emerge as the only two possible solution that satisfy the steady-state weak turbulence plasma kinetic equation. For the proton inverse power-law tail problem, a similar turbulent equilibrium solution can be conceived of, but instead of high-frequency Langmuir fluctuation, the theory involves low-frequency kinetic Alfvenic turbulence. The steady-state solution of the self-consistent proton kinetic equation and wave kinetic equation for Alfvenic waves can be found in order to obtain a self-consistent solution for the inverse power law tail distribution function.

  4. Pitch angle distributions of electrons at dipolarization sites during geomagnetic activity: THEMIS observations

    NASA Astrophysics Data System (ADS)

    Wang, Kaiti; Lin, Ching-Huei; Wang, Lu-Yin; Hada, Tohru; Nishimura, Yukitoshi; Turner, Drew L.; Angelopoulos, Vassilis

    2014-12-01

    Changes in pitch angle distributions of electrons with energies from a few eV to 1 MeV at dipolarization sites in Earth's magnetotail are investigated statistically to determine the extent to which adiabatic acceleration may contribute to these changes. Forty-two dipolarization events from 2008 and 2009 observed by Time History of Events and Macroscale Interactions during Substorms probes covering the inner plasma sheet from 8 RE to 12 RE during geomagnetic activity identified by the AL index are analyzed. The number of observed events with cigar-type distributions (peaks at 0° and 180°) decreases sharply below 1 keV after dipolarization because in many of these events, electron distributions became more isotropized. From above 1 keV to a few tens of keV, however, the observed number of cigar-type events increases after dipolarization and the number of isotropic events decreases. These changes can be related to the ineffectiveness of Fermi acceleration below 1 keV (at those energies, dipolarization time becomes comparable to electron bounce time). Model-calculated pitch angle distributions after dipolarization with the effect of betatron and Fermi acceleration tested indicate that these adiabatic acceleration mechanisms can explain the observed patterns of event number changes over a large range of energies for cigar events and isotropic events. Other factors still need to be considered to assess the observed increase in cigar events around 2 keV. Indeed, preferential directional increase/loss of electron fluxes, which may contribute to the formation of cigar events, was observed. Nonadiabatic processes to accelerate electrons in a parallel direction may also be important for future study.

  5. Application of iota and kappa carrageenans to traditional several food using modified cassava flour

    NASA Astrophysics Data System (ADS)

    Al-Baarri, A. N.; Legowo, A. M.; Rizqiati, H.; Widayat; Septianingrum, A.; Sabrina, H. N.; Arganis, L. M.; Saraswati, R. O.; Mochtar, Rr C. P. R.

    2018-01-01

    Carrageenan has been known well as hydrocolloids that forming viscous dispersions and gels when dispersed in water. The carrageenan has not been widely applied to traditional foods. Therefore, the aim of this research was to determine the effect of kappa and iota carrageenans in traditional food models using modified cassava flour, sugar, and coconut milk. The textural properties, i.e. hardness, cohesiveness, springiness and adhesiveness have been measured using texture analyzer. The study indicated that traditional food models added kappa carrageenan at 2% generated remarkably higher in the hardness, cohesiveness, and springiness than those added iota carrageenan. On the other hand, the reserve result were found in the adhesiveness parameter. As conclusion, kappa carrageenan scan be potentially used for producing traditional foods based on the hard-texture-oriented foods whereas iota carrageenan can be used for the traditional foods with better adhesiveness.

  6. Intermittent particle distribution in synthetic free-surface turbulent flows.

    PubMed

    Ducasse, Lauris; Pumir, Alain

    2008-06-01

    Tracer particles on the surface of a turbulent flow have a very intermittent distribution. This preferential concentration effect is studied in a two-dimensional synthetic compressible flow, both in the inertial (self-similar) and in the dissipative (smooth) range of scales, as a function of the compressibility C . The second moment of the concentration coarse grained over a scale r , n_{r};{2} , behaves as a power law in both the inertial and the dissipative ranges of scale, with two different exponents. The shapes of the probability distribution functions of the coarse-grained density n_{r} vary as a function of scale r and of compressibility C through the combination C/r;{kappa} (kappa approximately 0.5) , corresponding to the compressibility, coarse grained over a domain of scale r , averaged over Lagrangian trajectories.

  7. The relationship between diffuse auroral and plasma sheet electron distributions near local midnight

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Schumaker, T.L.; Gussenhoven, M.S.; Hardy, D.A.

    1989-08-01

    A study of the relationship between diffuse auroral and plasma sheet electron distributions in the energy range from 50 eV to 20 keV in the midnight region was conducted using data from the P78-1 and SCATHA satellites. From 1 1/2 years of data, 14 events were found where the polar-orbiting P78-1 satellite and the near-geosynchronous SCATHA satellite were approximately on the same magnetic field line simultaneously, with SCATHA in the plasma sheet and P78-1 in the diffuse auroral region. For all cases the spectra from the two satellites are in good quantitative agreement. For 13 of the 14 events themore » pitch angle distribution measured at P78-1 was isotropic for angles mapping into the loss cone at the SCATHA orbit. For one event the P78-1 electron flux decreased with pitch angle toward the field line direction. At SCATHA the distributions outside the loss cone were most commonly butterfly or pancake, although distributions peaked toward the field line were sometimes observed at energies below 1 keV. Electron distributions, as measured where there is isotropy within the loss cone but anisotropy outside the loss cone, are inconsistent with current theories for the scattering of cone for the distribution measured at SCATHA, the electron precipitation lifetimes were calculated for the 14 events. Because the distributions are anisotropic at pitch angles away from the loss cone, the calculated lifetimes significantly exceed the lifetimes in the limit when the flu is isotropic at all pitch angles. The computed precipitation lifetimes are found to be weakly dependent on magnetic activity. The average lifetimes exceed those for the case of isotropy at all pitch angles by a factor between 2 and 3 for {ital Kp}{le}2 and approximately 1.5 for {ital Kp}{gt}2. {copyright} American Geophysical Union 1989« less

  8. Manipulation of NF-KappaBetta Activity in the Macrophage Lineage as a Novel Therapeutic Approach

    DTIC Science & Technology

    2007-05-01

    Sadikot, J. W. Christman, and T. S. Blackwell. 2003. Bioluminescent detection of endotoxin effects on HIV-1 LTR-driven transcription in vivo. J...differences in proliferation rates, expression of downstream gene expression and effects mediated by altered macrophages on associated epithelial...kappaB activity within macrophages has significant effects on mammary ductal development. 15. SUBJECT TERMS NF-kappaB, macrophages, mammary ductal

  9. Evidence for activation of nuclear factor kappaB in obstructive sleep apnea.

    PubMed

    Yamauchi, Motoo; Tamaki, Shinji; Tomoda, Koichi; Yoshikawa, Masanori; Fukuoka, Atsuhiko; Makinodan, Kiyoshi; Koyama, Noriko; Suzuki, Takahiro; Kimura, Hiroshi

    2006-12-01

    Obstructive sleep apnea (OSA) is a risk factor for atherosclerosis, and atherosclerosis evolves from activation of the inflammatory cascade. We propose that activation of the nuclear factor kappaB (NF-kappaB), a key transcription factor in the inflammatory cascade, occurs in OSA. Nine age-matched, nonsmoking, and non-hypertensive men with OSA symptoms and seven similar healthy subjects were recruited for standard polysomnography followed by the collection of blood samples for monocyte nuclear p65 concentrations (OSA and healthy groups). In the OSA group, p65 and of monocyte production of tumor necrosis factor alpha (TNF-alpha) were measured at the same time and after the next night of continuous positive airway pressure (CPAP). p65 Concentrations in the OSA group were significantly higher than in the control group [median, 0.037 ng/microl (interquartile range, 0.034 to 0.051) vs 0.019 ng/microl (interquartile range, 0.013 to 0.032); p = 0.008], and in the OSA group were significantly correlated with apnea-hypopnea index and time spent below an oxygen saturation of 90% (r = 0.77 and 0.88, respectively) after adjustment for age and BMI. One night of CPAP resulted in a reduction in p65 [to 0.020 ng/mul (interquartile range, 0.010 to 0.036), p = 0.04] and levels of TNF-alpha production in cultured monocytes [16.26 (interquartile range, 7.75 to 24.85) to 7.59 ng/ml (interquartile range, 5.19 to 12.95), p = 0.01]. NF-kappaB activation occurs with sleep-disordered breathing. Such activation of NF-kappaB may contribute to the pathogenesis of atherosclerosis in OSA patients.

  10. Electronic structure and partial charge distribution of doxorubicin under different molecular environments

    NASA Astrophysics Data System (ADS)

    Poudel, Lokendra

    Doxorubicin (trade name Adriamycin, abbreviated DOX) is a well-known an- thracyclic chemotherapeutic used in treating a variety of cancers including acute leukemia, lymphoma, multiple myeloma, and a range of stomach, lung, bladder, bone, breast, and ovarian cancers. The purpose of the present work is to study electronic structure, partial charge distribution and interaction energy of DOX under different environments. It provides a framework for better understanding of bioactivity of DOX with DNA. While in this work, we focus on DOX -- DNA interactions; the obtained knowledge could be translated to other drug -- target interactions or biomolecular interactions. The electronic structure and partial charge distribution of DOX in three dierent molecular environments: isolated, solvated, and intercalated into a DNA complex,were studied by rst principles density functional methods. It is shown that the addition of solvating water molecules to DOX and the proximity and interaction with DNA has a signicant impact on the electronic structure as well as the partial charge distribution. The calculated total partial charges for DOX in the three models are 0.0, +0.123 and -0.06 electrons for the isolated, solvated, and intercalated state, respectively. Furthermore, by using the more accurate ab initio partial charge values on every atom in the models, signicant improvement in estimating the DOX-DNA interaction energy is obtained in conjunction with the NAnoscale Molecular Dynamics (NAMD) code. The electronic structure of the DOX-DNA is further elucidated by resolving the total density of states (TDOS) into dierent functional groups of DOX, DNA, water, co-crystallized Spermine molecule, and Na ions. The surface partial charge distribution in the DOX-DNA is calculated and displayed graphically. We conclude that the presence of the solvent as well as the details of the interaction geometry matter greatly in the determination of the stability of the DOX complexion. Ab initio

  11. Survey of radiation belt energetic electron pitch angle distributions based on the Van Allen Probes MagEIS measurements: Electron Pitch Angle Distributions

    DOE PAGES

    Shi, Run; Summers, Danny; Ni, Binbin; ...

    2016-12-30

    A statistical survey of electron pitch angle distributions (PADs) is performed based on the pitch angle-resolved flux observations from the Magnetic Electron Ion Spectrometer (MagEIS) instrument on board the Van Allen Probes during the period from 1 October 2012 to 1 May 2015. By fitting the measured PADs to a sin nα form, where α is the local pitch angle and n is the power law index, we investigate the dependence of PADs on electron kinetic energy, magnetic local time (MLT), the geomagnetic Kp index, and L shell. The difference in electron PADs between the inner and outer belt ismore » distinct. In the outer belt, the common averaged n values are less than 1.5, except for large values of the Kp index and high electron energies. The averaged n values vary considerably with MLT, with a peak in the afternoon sector and an increase with increasing L shell. In the inner belt, the averaged n values are much larger, with a common value greater than 2. The PADs show a slight dependence on MLT, with a weak maximum at noon. A distinct region with steep PADs lies in the outer edge of the inner belt where the electron flux is relatively low. The distance between the inner and outer belt and the intensity of the geomagnetic activity together determine the variation of PADs in the inner belt. Finally, besides being dependent on electron energy, magnetic activity, and L shell, the results show a clear dependence on MLT, with higher n values on the dayside.« less

  12. Survey of radiation belt energetic electron pitch angle distributions based on the Van Allen Probes MagEIS measurements: Electron Pitch Angle Distributions

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Shi, Run; Summers, Danny; Ni, Binbin

    A statistical survey of electron pitch angle distributions (PADs) is performed based on the pitch angle-resolved flux observations from the Magnetic Electron Ion Spectrometer (MagEIS) instrument on board the Van Allen Probes during the period from 1 October 2012 to 1 May 2015. By fitting the measured PADs to a sin nα form, where α is the local pitch angle and n is the power law index, we investigate the dependence of PADs on electron kinetic energy, magnetic local time (MLT), the geomagnetic Kp index, and L shell. The difference in electron PADs between the inner and outer belt ismore » distinct. In the outer belt, the common averaged n values are less than 1.5, except for large values of the Kp index and high electron energies. The averaged n values vary considerably with MLT, with a peak in the afternoon sector and an increase with increasing L shell. In the inner belt, the averaged n values are much larger, with a common value greater than 2. The PADs show a slight dependence on MLT, with a weak maximum at noon. A distinct region with steep PADs lies in the outer edge of the inner belt where the electron flux is relatively low. The distance between the inner and outer belt and the intensity of the geomagnetic activity together determine the variation of PADs in the inner belt. Finally, besides being dependent on electron energy, magnetic activity, and L shell, the results show a clear dependence on MLT, with higher n values on the dayside.« less

  13. Electron distributions upstream of the Comet Halley bow shock - Evidence for adiabatic heating

    NASA Technical Reports Server (NTRS)

    Larson, D. E.; Anderson, K. A.; Lin, R. P.; Carlson, C. W.; Reme, H.; Glassmeier, K. H.; Neubauer, F. M.

    1992-01-01

    Three-dimensional plasma electron (22 eV to 30 keV) observations upstream of Comet Halley bow shock, obtained by the RPA-1 COPERNIC (Reme Plasma Analyzer - Complete Positive Ion, Electron and Ram Negative Ion Measurements near Comet Halley) experiment on the Giotto spacecraft are reported. Besides electron distributions typical of the undisturbed solar wind and backstreaming electrons observed when the magnetic field line intersects the cometary bow shock, a new type of distribution, characterized by enhanced low energy (less than 100 eV) flux which peaks at 90-deg pitch angles is found. These are most prominent when the spacecraft is on field lines which pass close to but are not connected to the bow shock. The 90-deg pitch angle electrons appear to have been adiabatically heated by the increase in the magnetic field strength resulting from the compression of the upstream solar wind plasma by the cometary mass loading. A model calculation of this effect which agrees qualitatively with the observed 90-deg flux enhancements is presented.

  14. Transcriptional regulation of NADPH oxidase isoforms, Nox1 and Nox4, by nuclear factor-{kappa}B in human aortic smooth muscle cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Manea, Adrian, E-mail: adrian.manea@icbp.ro; Tanase, Laurentia I.; Raicu, Monica

    Inflammation-induced changes in the activity and expression of NADPH oxidases (Nox) play a key role in atherogenesis. The molecular mechanisms of Nox regulation are scantily elucidated. Since nuclear factor-{kappa}B (NF-{kappa}B) controls the expression of many genes associated to inflammation-related diseases, in this study we have investigated the role of NF-{kappa}B signaling in the regulation of Nox1 and Nox4 transcription in human aortic smooth muscle cells (SMCs). Cultured cells were exposed to tumor necrosis factor-{alpha} (TNF{alpha}), a potent inducer of both Nox and NF-{kappa}B, up to 24 h. Lucigenin-enhanced chemiluminescence and dichlorofluorescein assays, real-time polymerase chain reaction, and Western blot analysismore » showed that inhibition of NF-{kappa}B pathway reduced significantly the TNF{alpha}-dependent up-regulation of Nox-derived reactive oxygen species production, Nox1 and Nox4 expression. In silico analysis indicated the existence of typical NF-{kappa}B elements in the promoters of Nox1 and Nox4. Transient overexpression of p65/NF-{kappa}B significantly increased the promoter activities of both isoforms. Physical interaction of p65/NF-{kappa}B proteins with the predicted sites was demonstrated by chromatin immunoprecipitation assay. These findings demonstrate that NF-{kappa}B is an essential regulator of Nox1- and Nox4-containing NADPH oxidase in SMCs. Elucidation of the complex relationships between NF-{kappa}B and Nox enzymes may lead to a novel pharmacological strategy to reduce both inflammation and oxidative stress in atherosclerosis and its associated complications.« less

  15. Coordination of NF-kappaB and NFAT antagonism by the forkhead transcription factor Foxd1.

    PubMed

    Lin, Ling; Peng, Stanford L

    2006-04-15

    Forkhead transcription factors play critical roles in the maintenance of immune homeostasis. In this study, we demonstrate that this regulation most likely involves intricate interactions between the forkhead family members and inflammatory transcription factors: the forkhead member Foxd1 coordinates the regulation of the activity of two key inflammatory transcription factors, NF-AT and NF-kappaB, with Foxd1 deficiency resulting in multiorgan, systemic inflammation, exaggerated Th cell-derived cytokine production, and T cell proliferation in autologous MLRs. Foxd1-deficient T cells possess increased activity of both NF-AT and NF-kappaB: the former correlates with the ability of Foxd1 to regulate casein kinase 1, an NF-AT inhibitory kinase; the latter with the ability of Foxd1 to regulate Foxj1, which regulates the NF-kappaB inhibitory subunit IkappaB beta. Thus, Foxd1 modulates inflammatory reactions and prevents autoimmunity by directly regulating anti-inflammatory regulators of the NF-AT pathway, and by coordinating the suppression of the NF-kappaB pathway via Foxj1. These findings indicate the presence of a general network of forkhead proteins that enforce T cell quiescence.

  16. The lymphotoxin promoter is stimulated by HTLV-I tax activation of NF-kappa B in human T-cell lines.

    PubMed

    Paul, N L; Millet, I; Ruddle, N H

    1993-07-01

    The HTLV-I transcriptional activator tax was used to gain insight into the mechanism of lymphotoxin (LT; TNF-beta) gene induction. Tax-expressing cell lines produce LT biologic activity. An LT promoter (LT-293) CAT construct that contained an NF-kappa B site was active in the LT-producing C81-66-45 cell line, which contains defective HTLV-I but expresses tax. The observation that a mutated LT-kappa B construct (M1-CAT) was inactive in C81-66-45, confirmed the importance of NF-kappa B in LT gene expression. Tax was transfected into HTLV-I-negative human T-cell lines. Jurkat T cells stably expressing tax contained elevated levels of NF-kappa B that directly bound to the LT-kappa B site. Tax co-transfected with reporter constructs into Jurkat cells maximally activated HTLV-I-LTR-CAT and kappa B-fos-CAT and also activated LT-293 to a lesser extent. In JM T cells, tax induced LT-293 activity by two- to four-fold, though there was no induction of M1-CAT. The increase in LT-293 CAT activity mirrored the increase in LT biologic activity seen under these conditions. These studies, the first to demonstrate induction of LT promoter activity over basal levels, indicate that HTLV-I tax causes low-level activation of both endogenous LT and the LT promoter, at least in part through activation of NF-kappa B.

  17. Electron transport in furfural: dependence of the electron ranges on the cross sections and the energy loss distribution functions

    NASA Astrophysics Data System (ADS)

    Ellis-Gibbings, L.; Krupa, K.; Colmenares, R.; Blanco, F.; Muńoz, A.; Mendes, M.; Ferreira da Silva, F.; Limá Vieira, P.; Jones, D. B.; Brunger, M. J.; García, G.

    2016-09-01

    Recent theoretical and experimental studies have provided a complete set of differential and integral electron scattering cross section data from furfural over a broad energy range. The energy loss distribution functions have been determined in this study by averaging electron energy loss spectra for different incident energies and scattering angles. All these data have been used as input parameters for an event by event Monte Carlo simulation procedure to obtain the electron energy deposition patterns and electron ranges in liquid furfural. The dependence of these results on the input cross sections is then analysed to determine the uncertainty of the simulated values.

  18. The trapping and distribution of charge in polarized polymethylmethacrylate under electron-beam irradiation

    NASA Astrophysics Data System (ADS)

    Song, Z. G.; Gong, H.; Ong, C. K.

    1997-06-01

    A scanning electron microscope (SEM) mirror-image method (MIM) is employed to investigate the charging behaviour of polarized polymethylmethacrylate (PMMA) under electron-beam irradiation. An ellipsoid is used to model the trapped charge distribution and a fitting method is employed to calculate the total amount of the trapped charge and its distribution parameters. The experimental results reveal that the charging ability decreases with increasing applied electric field, which polarizes the PMMA sample, whereas the trapped charge distribution is elongated along the direction of the applied electric field and increases with increasing applied electric field. The charges are believed to be trapped in some localization states, of activation energy and radius estimated to be about 19.6 meV and 0022-3727/30/11/004/img6, respectively.

  19. Alpha Kappa Alpha Sorority's Reading Improvement Program for Minorities.

    ERIC Educational Resources Information Center

    Marable, June Morehead

    This document discusses the founding and establishment of Alpha Kappa Alpha Sorority's reading experience pilot project. The efforts of this project were aligned with those of Right to Read and Reading Is Fundamental (RIF). Because of the response from parents and children, plans are being made to increase present operations within the next…

  20. Site-directed mutagenesis study on DNA binding regions of the mouse homologue of Suppressor of Hairless, RBP-J kappa.

    PubMed Central

    Chung, C N; Hamaguchi, Y; Honjo, T; Kawaichi, M

    1994-01-01

    To map regions important for DNA binding of the mouse homologue of Suppressor of Hairless or RBP-J kappa protein, mutated mouse RBP-J kappa cDNAs were made by insertion of oligonucleotide linkers or base replacement. DNA binding assays using the mutated proteins expressed in COS cells showed that various mutations between 218 Arg and 227 Arg decreased the DNA binding activity drastically. The DNA binding activity was not affected by amino acid replacements within the integrase motif of the RBP-J kappa protein (230His-269His). Replacements between 291Arg and 323Tyr affected the DNA binding activity slightly but reproducibly. These results indicate that the region encompassing 218Arg-227Arg is critical for the DNA binding activity of RBP-J kappa. This region did not show any significant homology to motifs or domains of the previously described DNA binding proteins. Using a truncation mutant protein RBP-J kappa was shown to associate with DNA as a monomer. Images PMID:8065905

  1. Three component plasma electron distribution in the intermediate ionized coma of Comet Giacobini-Zinner

    NASA Astrophysics Data System (ADS)

    Zwickl, R. D.; Baker, D. N.; Bame, S. J.; Feldman, W. C.; Fuselier, S. A.; Huebner, W. F.; McComas, D. J.; Young, D. T.

    1986-04-01

    The observation of three distinct components of the electron distribution function measured in the intermediate ionized coma (IIC) and plasma tail of Comet Giacobini-Zinner is reported. It is believed that the cold component represents electrons produced close to the comet nucleus by ionization of cometary matter and subsequent cooling by Coulomb collisions. The second component also appears to be composed of electrons produced by photoionization of cometary neutrals, but sufficiently far from the nucleus that the distributions are largely unaffected by Coulomb interactions. The hot component is probably a population of electrons originating in the solar wind. Throughout the IIC, the electrostatic potential of the spacecraft was very low (less than 0.8 eV), implying that ICE generated very little impact-produced plasma during its passage.

  2. Mechanisms of Kappa Opioid Receptor Potentiation of Dopamine D2 Receptor Function in Quinpirole-Induced Locomotor Sensitization in Rats.

    PubMed

    Escobar, Angélica P; González, Marcela P; Meza, Rodrigo C; Noches, Verónica; Henny, Pablo; Gysling, Katia; España, Rodrigo A; Fuentealba, José A; Andrés, María E

    2017-08-01

    Increased locomotor activity in response to the same stimulus is an index of behavioral sensitization observed in preclinical models of drug addiction and compulsive behaviors. Repeated administration of quinpirole, a D2/D3 dopamine agonist, induces locomotor sensitization. This effect is potentiated and accelerated by co-administration of U69593, a kappa opioid receptor agonist. The mechanism underlying kappa opioid receptor potentiation of quinpirole-induced locomotor sensitization remains to be elucidated. Immunofluorescence anatomical studies were undertaken in mice brain slices and rat presynaptic synaptosomes to reveal kappa opioid receptor and D2R pre- and postsynaptic colocalization in the nucleus accumbens. Tonic and phasic dopamine release in the nucleus accumbens of rats repeatedly treated with U69593 and quinpirole was assessed by microdialysis and fast scan cyclic voltammetry. Anatomical data show that kappa opioid receptor and D2R colocalize postsynaptically in medium spiny neurons of the nucleus accumbens and the highest presynaptic colocalization occurs on the same dopamine terminals. Significantly reduced dopamine levels were observed in quinpirole, and U69593-quinpirole treated rats, explaining sensitization of D2R. Presynaptic inhibition induced by kappa opioid receptor and D2R of electrically evoked dopamine release was faster in U69593-quinpirole compared with quinpirole-repeatedly treated rats. Pre- and postsynaptic colocalization of kappa opioid receptor and D2R supports a role for kappa opioid receptor potentiating both the D2R inhibitory autoreceptor function and the inhibitory action of D2R on efferent medium spiny neurons. Kappa opioid receptor co-activation accelerates D2R sensitization by contributing to decrease dopamine release in the nucleus accumbens. © The Author 2017. Published by Oxford University Press on behalf of CINP.

  3. Inhibition of inhibitor of kappaB kinases stimulates hepatic stellate cell apoptosis and accelerated recovery from rat liver fibrosis.

    PubMed

    Oakley, Fiona; Meso, Muriel; Iredale, John P; Green, Karen; Marek, Carylyn J; Zhou, Xiaoying; May, Michael J; Millward-Sadler, Harry; Wright, Matthew C; Mann, Derek A

    2005-01-01

    Resolution of liver fibrosis is associated with clearance of hepatic myofibroblasts by apoptosis; development of strategies that promote this process in a selective way is therefore important. The aim of this study was to determine whether the inhibitor of kappaB kinase suppressor sulfasalazine stimulates hepatic myofibroblast apoptosis and recovery from fibrosis. Hepatic myofibroblasts were generated by culture activation of rat and human hepatic stellate cells. Fibrosis was established in rat livers by chronic injury with carbon tetrachloride followed by recovery with or without sulfasalazine (150 mg/kg) treatment. Treatment of hepatic stellate cells with sulfasalazine (0.5-2.0 mmol/L) induced apoptosis of activated rat and human hepatic stellate cells. A single in vivo administration of sulfasalazine promoted accelerated recovery from fibrosis as assessed by improved fibrosis score, selective clearance of smooth muscle alpha-actin-positive myofibroblasts, reduced hepatic procollagen I and tissue inhibitor of metalloproteinase 1 messenger RNA expression, and increased matrix metalloproteinase 2 activity. Mechanistic studies showed that sulfasalazine selectively blocks nuclear factor-kappaB-dependent gene transcription, inhibits hepatic stellate cell expression of Gadd45beta, stimulates phosphorylation of Jun N-terminal kinase 2, and promotes apoptosis by a mechanism that is prevented by the Jun N-terminal kinase inhibitor SP600125. As further evidence for a survival role for the inhibitor of kappaB kinase/nuclear factor-kappaB pathway in activated hepatic stellate cells, a highly selective cell-permeable peptide inhibitor of kappaB kinase activation also stimulated hepatic stellate cell apoptosis via a Jun N-terminal kinase-dependent mechanism. Inhibition of the inhibitor of kappaB kinase/nuclear factor-kappaB pathway is sufficient to increase the rate at which activated hepatic stellate cells undergo apoptosis both in vitro and in vivo, and drugs that

  4. Tomographic determination of the power distribution in electron beams

    DOEpatents

    Teruya, Alan T.; Elmer, John W.

    1996-01-01

    A tomographic technique for determining the power distribution of an electron beam using electron beam profile data acquired from a modified Faraday cup to create an image of the current density in high and low power beams. A refractory metal disk with a number of radially extending slits is placed above a Faraday cup. The beam is swept in a circular pattern so that its path crosses each slit in a perpendicular manner, thus acquiring all the data needed for a reconstruction in one circular sweep. Also, a single computer is used to generate the signals actuating the sweep, to acquire that data, and to do the reconstruction, thus reducing the time and equipment necessary to complete the process.

  5. Nonequilibrium distribution functions in electron transport: decoherence, energy redistribution and dissipation

    NASA Astrophysics Data System (ADS)

    Stegmann, Thomas; Ujsághy, Orsolya; Wolf, Dietrich E.

    2018-04-01

    A new statistical model for the combined effects of decoherence, energy redistribution and dissipation on electron transport in large quantum systems is introduced. The essential idea is to consider the electron phase information to be lost only at randomly chosen regions with an average distance corresponding to the decoherence length. In these regions the electron's energy can be unchanged or redistributed within the electron system or dissipated to a heat bath. The different types of scattering and the decoherence leave distinct fingerprints in the energy distribution functions. They can be interpreted as a mixture of unthermalized and thermalized electrons. In the case of weak decoherence, the fraction of thermalized electrons show electrical and thermal contact resistances. In the regime of incoherent transport the proposed model is equivalent to a Boltzmann equation. The model is applied to experiments with carbon nanotubes. The excellent agreement of the model with the experimental data allows to determine the scattering lengths of the system.

  6. Modeling electronic trap state distributions in nanocrystalline anatase

    NASA Astrophysics Data System (ADS)

    Le, Nam; Schweigert, Igor

    The charge transport properties of nanocrystalline TiO2 films, and thus the catalytic performance of devices that incorporate them, are affected strongly by the spatial and energetic distribution of localized electronic trap states. Such traps may arise from a variety of defects: Ti interstitials, O vacancies, step edges at surfaces, and grain boundaries. We have developed a procedure for applying density functional theory (DFT) and density functional tight binding (DFTB) calculations to characterize distributions of localized states arising from multiple types of defects. We have applied the procedure to investigate how the morphologies of interfaces between pairs of attached anatase nanoparticles determine the energies of trap states therein. Our results complement recent experimental findings that subtle changes in the morphology of highly porous TiO2 aerogel networks can have a dramatic effect on catalytic performance, which was attributed to changes in the distribution of trap states. This work was supported by the U.S. Naval Research Laboratory via the National Research Council and by the Office of Naval Research through the U.S. Naval Research Laboratory.

  7. Highly condensed fluorinated methacrylate hybrid material for transparent low-kappa passivation layer in LCD-TFT.

    PubMed

    Oh, Ji-Hoon; Kwak, Seung-Yeon; Yang, Seung-Cheol; Bae, Byeong-Soo

    2010-03-01

    Photocurable and highly condensed fluorinated methacrylate oligosiloxane, with a low dielectric constant (kappa = 2.54), was prepared by a nonhydrolytic sol-gel condensation reaction. The oligosiloxane resin was then spin-coated, photocured, and thermally baked in order to fabricate a fluorinated methacrylate hybrid material (FM hybrimer) thin film. This study investigated the application of this FM hybrimer film as a low-kappa passivation layer in LCD-based thin film transistors (TFT). It was found that a dielectric constant as low as kappa = 2.54 could be obtained, without introducing pores in the dense FM hybrimer films. This study compares FM hybrimer film characteristics with those required for passivation layers in LCD-TFTs, including thermal stability, optical transmittance, hydrophobicity, gap fill, and planarization effects as well as electrical insulation.

  8. Temperature anisotropy instabilities stimulated by the interplay of the core and halo electrons in space plasmas

    NASA Astrophysics Data System (ADS)

    Lazar, M.; Shaaban, S. M.; Fichtner, H.; Poedts, S.

    2018-02-01

    Two central components are revealed by electron velocity distributions measured in space plasmas, a thermal bi-Maxwellian core and a bi-Kappa suprathermal halo. A new kinetic approach is proposed to characterize the temperature anisotropy instabilities driven by the interplay of core and halo electrons. Suggested by the observations in the solar wind, direct correlations of these two populations are introduced as co-variations of the key parameters, e.g., densities, temperature anisotropies, and (parallel) plasma betas. The approach involving correlations enables the instability characterization in terms of either the core or halo parameters and a comparative analysis to depict mutual effects. In the present paper, the instability conditions are described for an extended range of plasma beta parameters, making the new dual approach relevant for a wide variety of space plasmas, including the solar wind and planetary magnetospheres.

  9. NASAwide electronic publishing system: Prototype STI electronic document distribution, stage-4 evaluation report

    NASA Technical Reports Server (NTRS)

    Tuey, Richard C.; Collins, Mary; Caswell, Pamela; Haynes, Bob; Nelson, Michael L.; Holm, Jeanne; Buquo, Lynn; Tingle, Annette; Cooper, Bill; Stiltner, Roy

    1996-01-01

    This evaluation report contains an introduction, seven chapters, and five appendices. The Introduction describes the purpose, conceptual frame work, functional description, and technical report server of the STI Electronic Document Distribution (EDD) project. Chapter 1 documents the results of the prototype STI EDD in actual operation. Chapter 2 documents each NASA center's post processing publication processes. Chapter 3 documents each center's STI software, hardware, and communications configurations. Chapter 7 documents STI EDD policy, practices, and procedures. The appendices, which arc contained in Part 2 of this document, consist of (1) STI EDD Project Plan, (2) Team members, (3) Phasing Schedules, (4) Accessing On-line Reports, and (5) Creating an HTML File and Setting Up an xTRS. In summary, Stage 4 of the NASAwide Electronic Publishing System is the final phase of its implementation through the prototyping and gradual integration of each NASA center's electronic printing systems, desktop publishing systems, and technical report servers to be able to provide to NASA's engineers, researchers, scientists, and external users the widest practicable and appropriate dissemination of information concerning its activities and the result thereof to their work stations.

  10. Physical mechanism causing rapid changes in ultrarelativistic electron pitch angle distributions right after a shock arrival: Evaluation of an electron dropout event: Drift Shell Splitting on the Dayside

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, X. -J.; Li, W.; Thorne, R. M.

    Three mechanisms have been proposed to explain relativistic electron flux depletions (dropouts) in the Earth's outer radiation belt during storm times: adiabatic expansion of electron drift shells due to a decrease in magnetic field strength, magnetopause shadowing and subsequent outward radial diffusion, and precipitation into the atmosphere (driven by EMIC wave scattering). Which mechanism predominates in causing electron dropouts commonly observed in the outer radiation belt is still debatable. In the present study, we evaluate the physical mechanism that may be primarily responsible for causing the sudden change in relativistic electron pitch angle distributions during a dropout event observed bymore » Van Allen Probes during the main phase of the 27 February 2014 storm. During this event, the phase space density of ultrarelativistic (>1MeV) electrons was depleted by more than 1 order of magnitude over the entire radial extent of the outer radiation belt (3 < L* < 5) in less than 6 h after the passage of an interplanetary shock. We model the electron pitch angle distribution under a compressed magnetic field topology based on actual solar wind conditions. Although these ultrarelativistic electrons exhibit highly anisotropic (peaked in 90°), energy-dependent pitch angle distributions, which appear to be associated with the typical EMIC wave scattering, comparison of the modeled electron distribution to electron measurements indicates that drift shell splitting is responsible for this rapid change in electron pitch angle distributions. This further indicates that magnetopause loss is the predominant cause of the electron dropout right after the shock arrival.« less

  11. Physical mechanism causing rapid changes in ultrarelativistic electron pitch angle distributions right after a shock arrival: Evaluation of an electron dropout event: Drift Shell Splitting on the Dayside

    DOE PAGES

    Zhang, X. -J.; Li, W.; Thorne, R. M.; ...

    2016-08-13

    Three mechanisms have been proposed to explain relativistic electron flux depletions (dropouts) in the Earth's outer radiation belt during storm times: adiabatic expansion of electron drift shells due to a decrease in magnetic field strength, magnetopause shadowing and subsequent outward radial diffusion, and precipitation into the atmosphere (driven by EMIC wave scattering). Which mechanism predominates in causing electron dropouts commonly observed in the outer radiation belt is still debatable. In the present study, we evaluate the physical mechanism that may be primarily responsible for causing the sudden change in relativistic electron pitch angle distributions during a dropout event observed bymore » Van Allen Probes during the main phase of the 27 February 2014 storm. During this event, the phase space density of ultrarelativistic (>1MeV) electrons was depleted by more than 1 order of magnitude over the entire radial extent of the outer radiation belt (3 < L* < 5) in less than 6 h after the passage of an interplanetary shock. We model the electron pitch angle distribution under a compressed magnetic field topology based on actual solar wind conditions. Although these ultrarelativistic electrons exhibit highly anisotropic (peaked in 90°), energy-dependent pitch angle distributions, which appear to be associated with the typical EMIC wave scattering, comparison of the modeled electron distribution to electron measurements indicates that drift shell splitting is responsible for this rapid change in electron pitch angle distributions. This further indicates that magnetopause loss is the predominant cause of the electron dropout right after the shock arrival.« less

  12. Tungsten phosphanylarylthiolato complexes [W{PhP(2-SC6H4)2-kappa3S,S',P} 2] and [W{P(2-SC6H4)3-kappa4S,S',S",P}2]: synthesis, structures and redox chemistry.

    PubMed

    Hildebrand, Alexandra; Lönnecke, Peter; Silaghi-Dumitrescu, Luminita; Hey-Hawkins, Evamarie

    2008-09-14

    PhP(2-SHC6H4)2 (PS2H2) reacts with WCl6 with reduction of tungsten to give the air-sensitive tungsten(IV) complex [W{PhP(2-SC6H4)2-kappa(3)S,S',P}2] (1). 1 is oxidised in air to [WO{PhPO(2-SC6H4)2-kappa(3)S,S',O}{PhP(2-SC6H4)2-kappa(3)S,S',P}] (2). The attempted synthesis of 2 by reaction of 1 with iodosobenzene as oxidising agent was unsuccessful. [W{P(2-SC6H4)3-kappa(4)S,S',S",P}2] (3) was formed in the reaction of P(2-SHC6H4)3 (PS3H3) with WCl6. The W(VI) complex 3 contains two PS3(3-) ligands, each coordinated in a tetradentate fashion resulting in a tungsten coordination number of eight. The reaction of 3 with AgBF4 yields the dinuclear tungsten complex [W2{P(2-SC6H4)3-kappa(4)S,S',S",P}3]BF4 (4). Complexes 1-4 were characterised by spectral methods and X-ray structure determination.

  13. System for tomographic determination of the power distribution in electron beams

    DOEpatents

    Elmer, J.W.; Teruya, A.T.; O'Brien, D.W.

    1995-01-17

    A tomographic technique is disclosed for measuring the current density distribution in electron beams using electron beam profile data acquired from a modified Faraday cup to create an image of the current density in high and low power beams. The modified Faraday cup includes a narrow slit and is rotated by a stepper motor and can be moved in the x, y and z directions. The beam is swept across the slit perpendicular thereto and controlled by deflection coils, and the slit rotated such that waveforms are taken every few degrees form 0[degree] to 360[degree] and the waveforms are recorded by a digitizing storage oscilloscope. Two-dimensional and three-dimensional images of the current density distribution in the beam can be reconstructed by computer tomography from this information, providing quantitative information about the beam focus and alignment. 12 figures.

  14. System for tomographic determination of the power distribution in electron beams

    DOEpatents

    Elmer, John W.; Teruya, Alan T.; O'Brien, Dennis W.

    1995-01-01

    A tomographic technique for measuring the current density distribution in electron beams using electron beam profile data acquired from a modified Faraday cup to create an image of the current density in high and low power beams. The modified Faraday cup includes a narrow slit and is rotated by a stepper motor and can be moved in the x, y and z directions. The beam is swept across the slit perpendicular thereto and controlled by deflection coils, and the slit rotated such that waveforms are taken every few degrees form 0.degree. to 360.degree. and the waveforms are recorded by a digitizing storage oscilloscope. Two-dimensional and three-dimensional images of the current density distribution in the beam can be reconstructed by computer tomography from this information, providing quantitative information about the beam focus and alignment.

  15. System for tomographic determination of the power distribution in electron beams

    DOEpatents

    Elmer, J.W.; Teruya, A.T.; O`Brien, D.W.

    1995-11-21

    A tomographic technique for measuring the current density distribution in electron beams using electron beam profile data acquired from a modified Faraday cup to create an image of the current density in high and low power beams. The modified Faraday cup includes a narrow slit and is rotated by a stepper motor and can be moved in the x, y and z directions. The beam is swept across the slit perpendicular thereto and controlled by deflection coils, and the slit rotated such that waveforms are taken every few degrees form 0{degree} to 360{degree} and the waveforms are recorded by a digitizing storage oscilloscope. Two-dimensional and three-dimensional images of the current density distribution in the beam can be reconstructed by computer tomography from this information, providing quantitative information about the beam focus and alignment. 12 figs.

  16. Nuclear IL-33 is a transcriptional regulator of NF-{kappa}B p65 and induces endothelial cell activation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Choi, Yeon-Sook; Park, Jeong Ae; Kim, Jihye

    2012-05-04

    Highlights: Black-Right-Pointing-Pointer IL-33 as nuclear factor regulated expression of ICAM-1 and VCAM-1. Black-Right-Pointing-Pointer Nuclear IL-33 increased the transcription of NF-{kappa}B p65 by binding to the p65 promoter. Black-Right-Pointing-Pointer Nuclear IL-33 controls NF-{kappa}B-dependent inflammatory responses. -- Abstract: Interleukin (IL)-33, an IL-1 family member, acts as an extracellular cytokine by binding its cognate receptor, ST2. IL-33 is also a chromatin-binding transcriptional regulator highly expressed in the nuclei of endothelial cells. However, the function of IL-33 as a nuclear factor is poorly defined. Here, we show that IL-33 is a novel transcriptional regulator of the p65 subunit of the NF-{kappa}B complex and ismore » involved in endothelial cell activation. Quantitative reverse transcriptase PCR and Western blot analyses indicated that IL-33 mediates the expression of intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 in endothelial cells basally and in response to tumor necrosis factor-{alpha}-treatment. IL-33-induced ICAM-1/VCAM-1 expression was dependent on the regulatory effect of IL-33 on the nuclear factor (NF)-{kappa}B pathway; NF-{kappa}B p65 expression was enhanced by IL-33 overexpression and, conversely, reduced by IL-33 knockdown. Moreover, NF-{kappa}B p65 promoter activity and chromatin immunoprecipitation analysis revealed that IL-33 binds to the p65 promoter region in the nucleus. Our data provide the first evidence that IL-33 in the nucleus of endothelial cells participates in inflammatory reactions as a transcriptional regulator of NF-{kappa}B p65.« less

  17. CARMA3 is overexpressed in colon cancer and regulates NF-{kappa}B activity and cyclin D1 expression

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Miao, Zhifeng; Zhao, Tingting; Wang, Zhenning

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer CARMA3 expression is elevated in colon cancers. Black-Right-Pointing-Pointer CARMA3 promotes proliferation and cell cycle progression in colon cancer cells. Black-Right-Pointing-Pointer CARMA3 upregulates cyclinD1 through NF-{kappa}B activation. -- Abstract: CARMA3 was recently reported to be overexpressed in cancers and associated with the malignant behavior of cancer cells. However, the expression of CARMA3 and its biological roles in colon cancer have not been reported. In the present study, we analyzed the expression pattern of CARMA3 in colon cancer tissues and found that CARMA3 was overexpressed in 30.8% of colon cancer specimens. There was a significant association between CARMA3 overexpression andmore » TNM stage (p = 0.0383), lymph node metastasis (p = 0.0091) and Ki67 proliferation index (p = 0.0035). Furthermore, knockdown of CARMA3 expression in HT29 and HCT116 cells with high endogenous expression decreased cell proliferation and cell cycle progression while overexpression of CARMA3 in LoVo cell line promoted cell proliferation and facilitated cell cycle transition. Further analysis showed that CARMA3 knockdown downregulated and its overexpression upregulated cyclin D1 expression and phospho-Rb levels. In addition, we found that CARMA3 depletion inhibited p-I{kappa}B levels and NF-{kappa}B activity and its overexpression increased p-I{kappa}B expression and NF-{kappa}B activity. NF-{kappa}B inhibitor BAY 11-7082 reversed the role of CARMA3 on cyclin D1 upregulation. In conclusion, our study found that CARMA3 is overexpressed in colon cancers and contributes to malignant cell growth by facilitating cell cycle progression through NF-{kappa}B mediated upregulation of cyclin D1.« less

  18. Revised Model of the Steady-state Solar Wind Halo Electron Velocity Distribution Function

    NASA Astrophysics Data System (ADS)

    Yoon, Peter H.; Kim, Sunjung; Choe, G. S.; moon, Y.-J.

    2016-08-01

    A recent study discussed the steady-state model for solar wind electrons during quiet time conditions. The electrons emanating from the Sun are treated in a composite three-population model—the low-energy Maxwellian core with an energy range of tens of eV, the intermediate ˜102-103 eV energy-range (“halo”) electrons, and the high ˜103-105 eV energy-range (“super-halo”) electrons. In the model, the intermediate energy halo electrons are assumed to be in resonance with transverse EM fluctuations in the whistler frequency range (˜102 Hz), while the high-energy super-halo electrons are presumed to be in steady-state wave-particle resonance with higher-frequency electrostatic fluctuations in the Langmuir frequency range (˜105 Hz). A comparison with STEREO and WIND spacecraft data was also made. However, ignoring the influence of Langmuir fluctuations on the halo population turns out to be an unjustifiable assumption. The present paper rectifies the previous approach by including both Langmuir and whistler fluctuations in the construction of the steady-state velocity distribution function for the halo population, and demonstrates that the role of whistler-range fluctuation is minimal unless the fluctuation intensity is arbitrarily raised. This implies that the Langmuir-range fluctuations, known as the quasi thermal noise, are important for both halo and super-halo electron velocity distribution.

  19. Influence of deoxynivalenol on NF-kappaB activation and IL-8 secretion in human intestinal Caco-2 cells.

    PubMed

    Van De Walle, Jacqueline; Romier, Béatrice; Larondelle, Yvan; Schneider, Yves-Jacques

    2008-04-01

    Deoxynivalenol (DON) is the most prevalent trichothecene mycotoxin in crops in Europe and North America. In human intestinal Caco-2 cells, DON activates the mitogen-activated protein kinases (MAPKs). We hypothesized a link between DON ingestion and intestinal inflammation, and used Caco-2 cells to assess the effects of DON, at plausible intestinal concentrations (250-10,000 ng/ml), on inflammatory mediators acting downstream the MAPKs cascade i.e. activation of nuclear factor-kappaB (NF-kappaB) and interleukin-8 (IL-8) secretion. In addition, Caco-2 cells were co-exposed to pro-inflammatory stimuli in order to mimic an inflamed intestinal epithelium. Dose-dependent increases in NF-kappaB activity and IL-8 secretion were observed, reaching 1.4- and 7.6-fold, respectively using DON at 10 microg/ml. Phosphorylation of inhibitor-kappaB (IkappaB) increased (1.6-fold) at DON levels <0.5 microg/ml. Exposure of Caco-2 cells to pro-inflammatory agents, i.e. 25 ng/ml interleukin-1beta, 100 ng/ml tumor necrosis factor-alpha or 10 microg/ml lipopolysaccharides, activated NF-kappaB and increased IL-8 secretion. Synergistic interactions between these stimuli and DON were observed. These data show that DON induces NF-kappaB activation and IL-8 secretion dose-dependently in Caco-2 cells, and this effect was accentuated upon pro-inflammatory stimulation, suggesting DON exposure could cause or exacerbate intestinal inflammation.

  20. Proteasome and NF-kappaB inhibiting phaeophytins from the green alga Cladophora fascicularis.

    PubMed

    Huang, Xinping; Li, Min; Xu, Bo; Zhu, Xiaobin; Deng, Zhiwei; Lin, Wenhan

    2007-03-21

    Chemical examination of the green alga Cladophora fascicularis resulted in the isolation and characterization of a new porphyrin derivative, porphyrinolactone (1), along with five known phaeophytins 2-6 and fourteen sterols and cycloartanes. The structure of 1 was determined on the basis of spectroscopic analyses and by comparison of its NMR data with those of known phaeophytins. Compounds 1-6 displayed moderate inhibition of tumor necrosis factor alpha (TNF-alpha) induced nuclear factor-kappaB (NF-kappaB) activation, while 2 and 4 displayed potential inhibitory activity toward proteasome chymotripsin-like activation. The primary structure-activity relationship was also discussed.

  1. Global Distribution of Net Electron Acceptance in Subseafloor Sediment

    NASA Astrophysics Data System (ADS)

    Fulfer, V. M.; Pockalny, R. A.; D'Hondt, S.

    2017-12-01

    We quantified the global distribution of net electron acceptance rates (e-/m2/year) in subseafloor sediment (>1.5 meters below seafloor [mbsf]) using (i) a modified version of the chemical-reaction-rate algorithm by Wang et al. (2008), (ii) physical properties and dissolved oxygen and sulfate data from interstitial waters of sediment cores collected by the Ocean Drilling Program, Integrated Ocean Drilling Program, International Ocean Discovery Program, and U.S. coring expeditions, and (iii) correlation of net electron acceptance rates to global oceanographic properties. Calculated net rates vary from 4.8 x 1019 e-/m2/year for slowly accumulating abyssal clay to 1.2 x 1023 e-/m2/year for regions of high sedimentation rate. Net electron acceptance rate correlates strongly with mean sedimentation rate. Where sedimentation rate is very low (e.g., 1 m/Myr), dissolved oxygen penetrates more than 70 mbsf and is the primary terminal electron acceptor. Where sedimentation rate is moderate (e.g., 3 to 60 m/Myr), dissolved sulfate penetrates as far as 700 mbsf and is the principal terminal electron acceptor. Where sedimentation rate is high (e.g., > 60 m/Myr), dissolved sulfate penetrates only meters, but is the principal terminal electron acceptor in subseafloor sediment to the depth of sulfate penetration. Because microbial metabolism continues at greater depths than the depth of sulfate penetration in fast-accumulating sediment, complete quantification of subseafloor metabolic rates will require consideration of other chemical species.

  2. Effects of age and sedentary lifestyle on skeletal muscle NF-kappaB signaling in men.

    PubMed

    Buford, Thomas W; Cooke, Matthew B; Manini, Todd M; Leeuwenburgh, Christiaan; Willoughby, Darryn S

    2010-05-01

    Nuclear factor kappa B (NF-kappaB) is a critical signaling molecule of disuse-induced skeletal muscle atrophy. However, few studies have carefully investigated whether similar pathways are modulated with physical activity and age. The present study examined lean mass, maximal force production, and skeletal muscle NF-kappaB signaling in 41 men categorized as sedentary (OS, N = 13, 63.85 +/- 6.59 year), physically active (OA, N = 14, 60.71 +/- 5.54 year), or young and sedentary (YS, N = 14, 21.35 +/- 3.84 year). Muscle tissue from the vastus lateralis was assayed for messenger RNA (mRNA) expression of the beta subunit of IkB kinase (IKKbeta), cytosolic protein content of phosphorylated inhibitor of kappa B alpha (pIKBalpha), and nuclear content of NF-kappaB subunits p50 and p65. When compared with YS, OS demonstrated age-related muscle atrophy and reduced isokinetic knee extension torque. Physical activity in older individuals preserved maximal isokinetic knee extension torque. OS muscle contained 50% more pIKBalpha than OA and 61% more pIKBalpha than YS. Furthermore, nuclear p65 was significantly elevated in OS compared with YS. OS muscle did not differ from either of the other two groups for nuclear p50 or for mRNA expression of IKKbeta. These results indicate that skeletal muscle content of nuclear-bound p65 is elevated by age in humans. The elevation in nuclear-bound p65 appears to be at least partially due to significant increases in pIKBalpha. A sedentary lifestyle appears to play some role in increased IKBalpha; however, further research is needed to identify downstream effects of this increase.

  3. Cylindrical and spherical solitary waves in an electron-acoustic plasma with vortex electron distribution

    NASA Astrophysics Data System (ADS)

    Demiray, Hilmi; El-Zahar, Essam R.

    2018-04-01

    We consider the nonlinear propagation of electron-acoustic waves in a plasma composed of a cold electron fluid, hot electrons obeying a trapped/vortex-like distribution, and stationary ions. The basic nonlinear equations of the above described plasma are re-examined in the cylindrical (spherical) coordinates by employing the reductive perturbation technique. The modified cylindrical (spherical) KdV equation with fractional power nonlinearity is obtained as the evolution equation. Due to the nature of nonlinearity, this evolution equation cannot be reduced to the conventional KdV equation. A new family of closed form analytical approximate solution to the evolution equation and a comparison with numerical solution are presented and the results are depicted in some 2D and 3D figures. The results reveal that both solutions are in good agreement and the method can be used to obtain a new progressive wave solution for such evolution equations. Moreover, the resulting closed form analytical solution allows us to carry out a parametric study to investigate the effect of the physical parameters on the solution behavior of the modified cylindrical (spherical) KdV equation.

  4. Experimental study of the spatial distributions of relativistic electron beams reflected and refracted by a thin foil

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Serov, A. V., E-mail: serov@x4u.lebedev.ru; Mamonov, I. A.

    2016-08-15

    Photographs of cross sections of an electron beam scattered from thin foils have been obtained on a dosimetric film. The procession of images makes it possible to obtain the spatial distribution of particles both reflected from a foil and passed through it. The spatial distribution of electrons incident on aluminum, copper, and lead foils, as well as on bimetallic foils composed of aluminum and lead layers and of aluminum and copper layers, has been measured. The effect of the material and thickness of the foil, as well as of the angle between the initial beam trajectory and the target plane,more » on the spatial distribution of electrons has been studied. The effect of the sequence of the metal layers in bimetallic foils on the distribution of beams has been analyzed. A 7.4-MeV microtron has been used as a source of electrons.« less

  5. Quiet-Time Suprathermal (˜0.1 - 200 keV) Electrons in the Solar Wind

    NASA Astrophysics Data System (ADS)

    Wang, Linghua; Yang, Liu; Tao, Jiawei; Zong, Qiugang; Li, Gang; Wimmer-Schweingruber, Robert; He, Jiansen; Tu, Chuanyi; Bale, Stuart

    2017-04-01

    We present a statistical survey of the energy spectrum of solar wind suprathermal (˜0.1-200 keV) electrons measured by the WIND 3DP instrument at 1 AU during quiet times at the minimum and maximum of solar cycles 23 and 24. The observed energy spectrum of both (beaming) strahl and (isotropic) halo electrons at ˜0.1-1.5 keV generally fits to a Kappa distribution function with an index κ and effective temperature Teff, while the observed energy spectrum of nearly isotropic superhalo electrons at ˜20-200 keV generally fits to a power-law function, J ˜ E-β. We find a strong positive correlation between κ and Teff for both strahl and halo electrons, and a strong positive correlation between the strahl density and halo density. In both solar cycles, κ is larger at solar minimum than at solar maximum for both strahl and halo electrons. For the superhalo population, the spectral index β ranges from ˜1.6 to ˜3.7 and the integrated density nsup ranges from 10-8 cm-3 to 10-5 cm-3, with no clear association with the sunspot number. In solar cycle 23 (24), the distribution of β has a broad maximum between 2.4 and 2.8 (2.0 and 2.4). All the strahl, halo and superhalo populations show no obvious correlation with the solar wind core population. These results reflect the nature of the generation of solar wind suprathermal electrons.

  6. Sample sizes and model comparison metrics for species distribution models

    Treesearch

    B.B. Hanberry; H.S. He; D.C. Dey

    2012-01-01

    Species distribution models use small samples to produce continuous distribution maps. The question of how small a sample can be to produce an accurate model generally has been answered based on comparisons to maximum sample sizes of 200 observations or fewer. In addition, model comparisons often are made with the kappa statistic, which has become controversial....

  7. Lentiviral-mediated targeted NF-kappaB blockade in dorsal spinal cord glia attenuates sciatic nerve injury-induced neuropathic pain in the rat.

    PubMed

    Meunier, Alice; Latrémolière, Alban; Dominguez, Elisa; Mauborgne, Annie; Philippe, Stéphanie; Hamon, Michel; Mallet, Jacques; Benoliel, Jean-Jacques; Pohl, Michel

    2007-04-01

    Neuropathic pain developing after peripheral nerve injury is associated with altered neuronal and glial cell functions in the spinal cord. Activated glia produces algogenic mediators, exacerbating pain. Among the different intracellular pathways possibly involved in the modified glial function, the nuclear factor kappaB (NF-kappaB) system is of particular interest, as numerous genes encoding inflammation- and pain-related molecules are controlled by this transcription factor. NF-kappaB is a pleiotropic factor also involved in central nervous system homeostasy. To study its role in chronic pain, it is thus essential to inhibit the NF-kappaB pathway selectively in activated spinal glial cells. Here, we show that when restricted to spinal cord and targeted to glial cells, lentiviral vector-mediated delivery of NF-kappaB super- repressor IkappaBalpha resulted in an inhibition of the NF-kappaB pathway activated in the rat spinal cord after sciatic nerve injury (chronic constriction injury, CCI). Concomitantly, IkappaBalpha overproduction prevented the enhanced expression of interleukin-6 and of inducible nitric oxide synthase associated with chronic constriction injury and resulted in prolonged antihyperalgesic and antiallodynic effects. These data show that targeted blockade of NF-kappaB activity in spinal glia efficiently alleviates pain behavior in CCI rats, demonstrating the active participation of the glial NF-kappaB pathway in the development of neuropathic pain after peripheral nerve injury.

  8. Tomographic determination of the power distribution in electron beams

    DOEpatents

    Teruya, A.T.; Elmer, J.W.

    1996-12-10

    A tomographic technique for determining the power distribution of an electron beam using electron beam profile data acquired from a modified Faraday cup to create an image of the current density in high and low power beams is disclosed. A refractory metal disk with a number of radially extending slits is placed above a Faraday cup. The beam is swept in a circular pattern so that its path crosses each slit in a perpendicular manner, thus acquiring all the data needed for a reconstruction in one circular sweep. Also, a single computer is used to generate the signals actuating the sweep, to acquire that data, and to do the reconstruction, thus reducing the time and equipment necessary to complete the process. 4 figs.

  9. Effects of kappa opioid agonists alone and in combination with cocaine on heart rate and blood pressure in conscious squirrel monkeys.

    PubMed

    Schindler, Charles W; Graczyk, Zofi; Gilman, Joanne P; Negus, S Stevens; Bergman, Jack; Mello, Nancy K; Goldberg, Steven R

    2007-12-08

    As kappa agonists have been proposed as treatments for cocaine abuse, the cardiovascular effects of the kappa opioid receptor agonists ethylketocyclazocine (EKC) and enadoline were investigated in conscious squirrel monkeys. Both EKC and enadoline increased heart rate with little effect on blood pressure. This effect appeared to be specific for kappa receptors as the mu opioid agonist morphine did not mimic the effects of the kappa agonists. The opioid antagonist naltrexone, at a dose of 1.0 mg/kg, blocked the effect of EKC. An action at both central and peripheral receptors may be responsible for the heart rate increase following kappa agonist treatment. The ganglionic blocker chlorisondamine partially antagonized the effect of EKC on heart rate, suggesting central involvement, while the peripherally-acting agonist ICI 204,448 ((+/-)-1-[2,3- (Dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol hydrochloride) also increased heart rate, supporting a peripheral site of action. When given in combination with cocaine, EKC produced effects that were sub-additive, suggesting that the kappa agonists may be used safely as cocaine abuse treatments.

  10. Transverse Momentum Distributions of Electron in Simulated QED Model

    NASA Astrophysics Data System (ADS)

    Kaur, Navdeep; Dahiya, Harleen

    2018-05-01

    In the present work, we have studied the transverse momentum distributions (TMDs) for the electron in simulated QED model. We have used the overlap representation of light-front wave functions where the spin-1/2 relativistic composite system consists of spin-1/2 fermion and spin-1 vector boson. The results have been obtained for T-even TMDs in transverse momentum plane for fixed value of longitudinal momentum fraction x.

  11. Total-scattering pair-distribution function of organic material from powder electron diffraction data.

    PubMed

    Gorelik, Tatiana E; Schmidt, Martin U; Kolb, Ute; Billinge, Simon J L

    2015-04-01

    This paper shows that pair-distribution function (PDF) analyses can be carried out on organic and organometallic compounds from powder electron diffraction data. Different experimental setups are demonstrated, including selected area electron diffraction and nanodiffraction in transmission electron microscopy or nanodiffraction in scanning transmission electron microscopy modes. The methods were demonstrated on organometallic complexes (chlorinated and unchlorinated copper phthalocyanine) and on purely organic compounds (quinacridone). The PDF curves from powder electron diffraction data, called ePDF, are in good agreement with PDF curves determined from X-ray powder data demonstrating that the problems of obtaining kinematical scattering data and avoiding beam damage of the sample are possible to resolve.

  12. High-level replication of human immunodeficiency virus in thymocytes requires NF-kappaB activation through interaction with thymic epithelial cells.

    PubMed

    Chêne, L; Nugeyre, M T; Barré-Sinoussi, F; Israël, N

    1999-03-01

    We have previously demonstrated that interaction of infected thymocytes with autologous thymic epithelial cells (TEC) is a prerequisite for a high level of human immunodeficiency virus type 1 (HIV-1) replication in thymocytes (M. Rothe, L. Chêne, M. Nugeyre, F. Barré-Sinoussi, and N. Israël, J. Virol. 72:5852-5861, 1998). We report here that this activation of HIV replication takes place at the transcriptional level through activation of the Rel/NF-kappaB transcription factors. We first demonstrate that an HIV-1 provirus (SF-2 strain) very effectively replicates in thymocytes cocultured with TEC whereas this provirus, with kappaB sites deleted, fails to replicate. We provide evidence that several NF-kappaB complexes are constitutively found in the nuclei of thymocytes either freshly isolated from the thymus or maintained in coculture with autologous or heterologous TEC. The prevalent complex is the heterodimer p50-p65. NF-kappaB activity is tightly correlated with the transcriptional activity of a long terminal repeat (LTR) of HIV-1 transfected in thymocytes. The cotransfection of this LTR with a mutated IkappaBalpha molecule formally demonstrates that LTR transactivation is regulated by members of the Rel/NF-kappaB family in thymocytes. We also showed that tumor necrosis factor (TNF) and to a lesser extent interleukin-1 (IL-1), secreted within the coculture, induce NF-kappaB activity and a correlative LTR transactivation. However IL-7, a crucial factor for thymopoiesis that is secreted mainly by TEC, is a necessary cofactor for NF-kappaB activation elicited by TNF or IL-1. Together, these data indicate that NF-kappaB activation, required for a high level of HIV replication in thymocytes, is regulated in a specific manner in the thymic microenvironment which provides the necessary cytokines: TNF, IL-1, and IL-7.

  13. NF-{kappa}B signaling is activated and confers resistance to apoptosis in three-dimensionally cultured EGFR-mutant lung adenocarcinoma cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sakuma, Yuji, E-mail: ysakuma@gancen.asahi.yokohama.jp; Yamazaki, Yukiko; Nakamura, Yoshiyasu

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer EGFR-mutant cells in 3D culture resist EGFR inhibition compared with suspended cells. Black-Right-Pointing-Pointer Degradation of I{kappa}B and activation of NF-{kappa}B are observed in 3D-cultured cells. Black-Right-Pointing-Pointer Inhibiting NF-{kappa}B enhances the efficacy of the EGFR inhibitor in 3D-cultured cells. -- Abstract: Epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma cells in suspension undergo apoptosis to a greater extent than adherent cells in a monolayer when EGFR autophosphorylation is inhibited by EGFR tyrosine kinase inhibitors (TKIs). This suggests that cell adhesion to a culture dish may activate an anti-apoptotic signaling pathway other than the EGFR pathway. Since the microenvironment of cellsmore » cultured in a monolayer are substantially different to that of cells existing in three-dimension (3D) in vivo, we assessed whether two EGFR-mutant lung adenocarcinoma cell lines, HCC827 and H1975, were more resistant to EGFR TKI-induced apoptosis when cultured in a 3D extracellular matrix (ECM) as compared with in suspension. The ECM-adherent EGFR-mutant cells in 3D were significantly less sensitive to treatment with WZ4002, an EGFR TKI, than the suspended cells. Further, a marked degradation of I{kappa}B{alpha}, the inhibitor of nuclear factor (NF)-{kappa}B, was observed only in the 3D-cultured cells, leading to an increase in the activation of NF-{kappa}B. Moreover, the inhibition of NF-{kappa}B with pharmacological inhibitors enhanced EGFR TKI-induced apoptosis in 3D-cultured EGFR-mutant cells. These results suggest that inhibition of NF-{kappa}B signaling would render ECM-adherent EGFR-mutant lung adenocarcinoma cells in vivo more susceptible to EGFR TKI-induced cell death.« less

  14. Spatial distribution of fluorescent light emitted from neon and nitrogen excited by low energy electron beams

    NASA Astrophysics Data System (ADS)

    Morozov, A.; Krücken, R.; Ulrich, A.; Wieser, J.

    2006-11-01

    Side-view intensity profiles of fluorescent light were measured for neon and nitrogen excited with 12keV electron beams at gas pressures from 250to1400hPa. The intensity profiles were compared with theoretical profiles calculated using the CASINO program which performs Monte Carlo simulations of electron scattering. It was assumed that the spatial distribution of fluorescent intensity is directly proportional to the spatial distribution of energy loss by primary electrons. The comparison shows good correlation of experimental data and the results of numeric simulations.

  15. NF-kappaB specifically activates BMP-2 gene expression in growth plate chondrocytes in vivo and in a chondrocyte cell line in vitro.

    PubMed

    Feng, Jian Q; Xing, Lianping; Zhang, Jiang-Hong; Zhao, Ming; Horn, Diane; Chan, Jeannie; Boyce, Brendan F; Harris, Stephen E; Mundy, Gregory R; Chen, Di

    2003-08-01

    Bone morphogenetic protein-2 (BMP-2) regulates growth plate chondrogenesis during development and postnatal bone growth, but the control mechanisms of BMP-2 expression in growth plate chondrocytes are unknown. Here we have used both in vitro and in vivo approaches to demonstrate that transcription factor, NF-kappaB, regulates BMP-2 gene expression in chondrocytes. Two putative NF-kappaB response elements were found in the -2712/+165 region of the BMP-2 gene. Cotransfection of mutant I-kappaBalpha expression plasmids with BMP-2 promoter-luciferase reporters into TMC-23 chondrocyte cell line suppressed BMP-2 transcription. Mutations in NF-kappaB response elements in the BMP-2 gene lead to decreases in BMP-2 promoter activity. Electrophoretic mobility shift assay using nuclear extracts from TMC-23 chondrocytic cells revealed that the NF-kappaB subunits p50 and p65 bound to the NF-kappaB response elements of the BMP-2 gene. Thus, NF-kappaB may positively regulate BMP-2 gene transcription. Consistent with these findings, expression of BMP-2 mRNA was significantly reduced in growth plate chondrocytes in NF-kappaB p50/p52 dKO mice, which associated with decreased numbers of 5-bromo-2'-deoxyuridine (BrdUrd)-positive cells in the proliferating zone of growth plate in these mice. Therefore, in postnatal growth plate chondrocytes, expression of BMP-2 is regulated by NF-kappaB, which may play an important role in chondrogenesis.

  16. Resolving runaway electron distributions in space, time, and energy

    DOE PAGES

    Paz-Soldan, Carlos; Cooper, C. M.; Aleynikov, P.; ...

    2018-05-01

    Areas of agreement and disagreement with present-day models of RE evolution are revealed by measuring MeV-level bremsstrahlung radiation from runaway electrons (REs) with a pinhole camera. Spatially-resolved measurements localize the RE beam, reveal energy-dependent RE transport, and can be used to perform full two-dimensional (energy and pitch-angle) inversions of the RE phase space distribution. Energy-resolved measurements find qualitative agreement with modeling on the role of collisional and synchrotron damping in modifying the RE distribution shape. Measurements are consistent with predictions of phase-space attractors that accumulate REs, with non-monotonic features observed in the distribution. Temporally-resolved measurements find qualitative agreement with modelingmore » on the impact of collisional and synchrotron damping in varying the RE growth and decay rate. Anomalous RE loss is observed and found to be largest at low energy. As a result, possible roles for kinetic instability or spatial transport to resolve these anomalies are discussed.« less

  17. Resolving runaway electron distributions in space, time, and energy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Paz-Soldan, Carlos; Cooper, C. M.; Aleynikov, P.

    Areas of agreement and disagreement with present-day models of RE evolution are revealed by measuring MeV-level bremsstrahlung radiation from runaway electrons (REs) with a pinhole camera. Spatially-resolved measurements localize the RE beam, reveal energy-dependent RE transport, and can be used to perform full two-dimensional (energy and pitch-angle) inversions of the RE phase space distribution. Energy-resolved measurements find qualitative agreement with modeling on the role of collisional and synchrotron damping in modifying the RE distribution shape. Measurements are consistent with predictions of phase-space attractors that accumulate REs, with non-monotonic features observed in the distribution. Temporally-resolved measurements find qualitative agreement with modelingmore » on the impact of collisional and synchrotron damping in varying the RE growth and decay rate. Anomalous RE loss is observed and found to be largest at low energy. As a result, possible roles for kinetic instability or spatial transport to resolve these anomalies are discussed.« less

  18. The discriminative effects of the kappa-opioid hallucinogen salvinorin A in nonhuman primates: dissociation from classic hallucinogen effects.

    PubMed

    Butelman, Eduardo R; Rus, Szymon; Prisinzano, Thomas E; Kreek, Mary Jeanne

    2010-06-01

    The widely available hallucinogen salvinorin A is a unique example of a plant-derived compound selective for kappa-opioid receptors and may produce effects distinct from those of other compounds with classic hallucinogenic or dissociative properties which are also abused in humans. The objective of this study is to characterize the salvinorin A discriminative cue in nonhuman primates with high kappa-receptor genetic homology to humans. Adult rhesus monkeys (n = 3) were trained to discriminate salvinorin A (0.015 mg/kg, s.c.) from vehicle, in a food-reinforced operant discrimination assay. Parallel studies, using unconditioned behavioral endpoints (facial relaxation and ptosis) also evaluated the kappa-opioid receptor mediation of salvinorin A in vivo function. Monkeys trained to discriminate salvinorin A generalized structurally diverse, centrally penetrating kappa-agonists (bremazocine, U69,593, and U50,488). By contrast, mu- and delta-opioid agonists (fentanyl and SNC80, respectively) were not generalized, nor were the serotonergic 5HT2 hallucinogen psilocybin or the dissociative N-methyl-D-aspartic acid antagonist, ketamine. The discriminative effects of salvinorin A were blocked by the opioid antagonist quadazocine (0.32 mg/kg), but not by the 5HT2 antagonist ketanserin (0.1 mg/kg). Consistent with these findings, salvinorin and kappa-agonists (e.g., U69,593) produce effects in the unconditioned endpoints (e.g., ptosis), whereas psilocybin was inactive. These findings support the conclusion that the interoceptive/discriminative cue produced by salvinorin A is mediated by agonism at kappa-receptors and is mechanistically distinct from that produced by a classic serotonergic hallucinogen.

  19. Kappa Agonists as a Novel Therapy for Menopausal Hot Flashes

    PubMed Central

    Oakley, Amy E.; Steiner, Robert A.; Chavkin, Charles; Clifton, Donald K.; Ferrara, Laura K.; Reed, Susan D.

    2015-01-01

    Objective Postmenopausal hot flash etiology is poorly understood, making it difficult to develop and target ideal therapies. A network of hypothalamic estrogen-sensitive neurons producing Kisspeptin, Neurokinin B, and Dynorphin (KNDy neurons), located adjacent to the thermoregulatory center, regulate pulsatile secretion of GnRH and LH. Dynorphin may inhibit this system by binding kappa opioid receptors within the vicinity of KNDy neurons. We hypothesize that hot flashes are reduced by KNDy neuron manipulation. Methods A double-blind, cross-over, placebo-controlled pilot study evaluated the effect of a kappa agonist (KA).Hot flash frequency was the primary outcome. Twelve healthy postmenopausal women with moderate-severe hot flashes, ages 48-60 years, were randomized. Eight women with sufficient baseline hot flashes for statistical analysis completed all 3 interventions: placebo, standard Pentazocine/Naloxone (50/0.5 mg) or low-dose Pentazocine/Naloxone (25/0.25 mg). In an inpatient research setting, each participant received the 3 interventions, in randomized order, on 3 separate days. On each day, an intravenous catheter was inserted for luteinizing hormone (LH) blood sampling, and skin conductance and Holter monitors were placed. Subjective hot flash frequency and severity were recorded. Results Mean hot flash frequency 2-7 hours following therapy initiation was lower than that for placebo (KA standard-dose: 4.75 ± 0.67; KA low-dose: 4.50 ± 0.57; and placebo: 5.94 ± 0.78 hot flashes/5 hours; p =0.025). Hot flash intensity did not vary between interventions. LH pulsatility mirrored objective hot flashes in some, but not all women. Conclusions This pilot suggests that kappa agonists may affect menopausal vasomotor symptoms. PMID:25988798

  20. Distribution and dynamics of electron transport complexes in cyanobacterial thylakoid membranes☆

    PubMed Central

    Liu, Lu-Ning

    2016-01-01

    The cyanobacterial thylakoid membrane represents a system that can carry out both oxygenic photosynthesis and respiration simultaneously. The organization, interactions and mobility of components of these two electron transport pathways are indispensable to the biosynthesis of thylakoid membrane modules and the optimization of bioenergetic electron flow in response to environmental changes. These are of fundamental importance to the metabolic robustness and plasticity of cyanobacteria. This review summarizes our current knowledge about the distribution and dynamics of electron transport components in cyanobacterial thylakoid membranes. Global understanding of the principles that govern the dynamic regulation of electron transport pathways in nature will provide a framework for the design and synthetic engineering of new bioenergetic machinery to improve photosynthesis and biofuel production. This article is part of a Special Issue entitled: Organization and dynamics of bioenergetic systems in bacteria, edited by Conrad Mullineaux. PMID:26619924

  1. Presynaptic inhibition of diverse afferents to the locus ceruleus by kappa-opiate receptors: a novel mechanism for regulating the central norepinephrine system.

    PubMed

    Kreibich, Arati; Reyes, Beverly A S; Curtis, Andre L; Ecke, Laurel; Chavkin, Charles; Van Bockstaele, Elisabeth J; Valentino, Rita J

    2008-06-18

    The norepinephrine nucleus, locus ceruleus (LC), is activated by diverse stimuli and modulates arousal and behavioral strategies in response to these stimuli through its divergent efferent system. Afferents communicating information to the LC include excitatory amino acids (EAAs), corticotropin-releasing factor (CRF), and endogenous opioids acting at mu-opiate receptors. Because the LC is also innervated by the endogenous kappa-opiate receptor (kappa-OR) ligand dynorphin and expresses kappa-ORs, this study investigated kappa-OR regulation of LC neuronal activity in rat. Immunoelectron microscopy revealed a prominent localization of kappa-ORs in axon terminals in the LC that also contained either the vesicular glutamate transporter or CRF. Microinfusion of the kappa-OR agonist (trans)-3,4-dichloro-N-methyl-N-[2-1-pyrrolidinyl)-cyclo-hexyl] benzeneacetamide (U50488) into the LC did not alter LC spontaneous discharge but attenuated phasic discharge evoked by stimuli that engage EAA afferents to the LC, including sciatic nerve stimulation and auditory stimuli and the tonic activation associated with opiate withdrawal. Inhibitory effects of the kappa-OR agonist were not restricted to EAA afferents, as U50488 also attenuated tonic LC activation by hypotensive stress, an effect mediated by CRF afferents. Together, these results indicate that kappa-ORs are poised to presynaptically inhibit diverse afferent signaling to the LC. This is a novel and potentially powerful means of regulating the LC-norepinephrine system that can impact on forebrain processing of stimuli and the organization of behavioral strategies in response to environmental stimuli. The results implicate kappa-ORs as a novel target for alleviating symptoms of opiate withdrawal, stress-related disorders, or disorders characterized by abnormal sensory responses, such as autism.

  2. REVISED MODEL OF THE STEADY-STATE SOLAR WIND HALO ELECTRON VELOCITY DISTRIBUTION FUNCTION

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yoon, Peter H.; Kim, Sunjung; Choe, G. S.

    2016-08-01

    A recent study discussed the steady-state model for solar wind electrons during quiet time conditions. The electrons emanating from the Sun are treated in a composite three-population model—the low-energy Maxwellian core with an energy range of tens of eV, the intermediate ∼10{sup 2}–10{sup 3} eV energy-range (“halo”) electrons, and the high ∼10{sup 3}–10{sup 5} eV energy-range (“super-halo”) electrons. In the model, the intermediate energy halo electrons are assumed to be in resonance with transverse EM fluctuations in the whistler frequency range (∼10{sup 2} Hz), while the high-energy super-halo electrons are presumed to be in steady-state wave–particle resonance with higher-frequency electrostaticmore » fluctuations in the Langmuir frequency range (∼10{sup 5} Hz). A comparison with STEREO and WIND spacecraft data was also made. However, ignoring the influence of Langmuir fluctuations on the halo population turns out to be an unjustifiable assumption. The present paper rectifies the previous approach by including both Langmuir and whistler fluctuations in the construction of the steady-state velocity distribution function for the halo population, and demonstrates that the role of whistler-range fluctuation is minimal unless the fluctuation intensity is arbitrarily raised. This implies that the Langmuir-range fluctuations, known as the quasi thermal noise, are important for both halo and super-halo electron velocity distribution.« less

  3. Distribution of electron density in charged Li@C60 complexes

    NASA Astrophysics Data System (ADS)

    Sadlej-Sosnowska, Nina; Mazurek, Aleksander P.

    2013-08-01

    The Letter is an expanded commentary to the paper 'Fullerene as an electron buffer: charge transfer in Li@C60', by Pavanello and co-authors [8]. We calculated the electron density distribution in the space inside and outside the fullerene cage in Li@C60 complexes differing in total charge, based on Gauss's law. It allowed us to determine the charges contained inside surfaces isomorphic with the fullerene cage and contracted or enlarged with respect to the latter. For every complex, a surface was found in the vicinity of the central Li atom such that the charge enclosed within it was equal to +1.

  4. Escherichia coli K1 inhibits proinflammatory cytokine induction in monocytes by preventing NF-kappaB activation.

    PubMed

    Selvaraj, Suresh K; Prasadarao, Nemani V

    2005-08-01

    Phagocytes are well-known effectors of the innate immune system to produce proinflammatory cytokines and chemokines such as tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, and IL-8 during infections. Here, we show that infection of monocytes with wild-type Escherichia coli K1, which causes meningitis in neonates, suppresses the production of cytokines and chemokines (TNF-alpha, regulated on activation, normal T expressed and secreted, macrophage-inflammatory protein-1beta, IL-1beta, and IL-8). In contrast, infection of monocytes with a mutant E. coli, which lacks outer membrane protein A (OmpA- E. coli) resulted in robust production of cytokines and chemokines. Wild-type E. coli K1 (OmpA+ E. coli) prevented the phosphorylation and its degradation of inhibitor of kappaB, thereby blocking the translocation of nuclear factor (NF)-kappaB to the nucleus. OmpA+ E. coli-infected cells, subsequently subjected to lipopolysaccharide challenge, were crippled severely in their ability to activate NF-kappaB to induce cytokine/chemokine production. Selective inhibitors of the extracellular signal-regulated kinase (ERK) 1/2 pathway and p38 mitogen-activated protein kinase (MAPK), but not Jun N-terminal kinase, significantly reduced the activation of NF-kappaB and the production of cytokines and chemokines induced by OmpA- E. coli, indicating a role for these kinases in the NF-kappaB/cytokine pathway. It is interesting that the phosphorylation of ERK 1/2 and p38 MAPK was notably reduced in monocytes infected with OmpA+ E. coli when compared with monocytes infected with OmpA- E. coli, suggesting that the modulation of upstream events common for NF-kappaB and MAPKs by the bacterium is possible. The ability of OmpA+ E. coli K1 to inhibit the macrophage response temporarily may enable bacterial survival and growth within the host for the onset of meningitis by E. coli K1.

  5. The suppression of radiation-induced NF-{kappa}B activity by dexamethasone correlates with increased cell death in vivo

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nam, Seon Young; Chung, Hee-Yong

    2005-10-21

    In this study, we show that dexamethasone treatment increases ionizing radiation-induced cell death by inducing the inhibitory {kappa}B{alpha} (I{kappa}B{alpha}) pathway in mice. The effect of dexamethasone on radiation-induced cell death was assessed by changes in total spleen cellularity and bone marrow colony-forming unit-granulocyte-macrophage (CFU-GM) contents after total body irradiation. While in vivo treatment of mice with dexamethasone alone (1 mg/kg/day, for 2 days) failed to elicit cell death in spleen cells, the combined treatment with dexamethasone (1 mg/kg/day, for 2 days) and {gamma}-rays (1 or 5 Gy) caused a 50-80% reduction in total cellularity in spleen and CFU-GM contents inmore » bone marrow. These results demonstrate that dexamethasone has a synergistic effect on radiation-induced cellular damages in vivo. Immunoblot analysis showed that dexamethasone treatment significantly increases I{kappa}B{alpha} expression in the spleens of irradiated mice. In addition, the dexamethasone treatment significantly reduced radiation-induced nuclear translocation of the nucleus factor-{kappa}B in the spleens of irradiated mice. These results indicate that dexamethasone treatment in vivo may increase radiation-induced cell damages by increasing I{kappa}B{alpha} expression in hematopoietic organs such as spleen and bone marrow.« less

  6. Styrene induces an inflammatory response in human lung epithelial cells via oxidative stress and NF-{kappa}B activation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Roeder-Stolinski, Carmen; Fischaeder, Gundula; Oostingh, Gertie Janneke

    2008-09-01

    Styrene is a volatile organic compound (VOC) that is widely used as a solvent in many industrial settings. Chronic exposure to styrene can result in irritation of the mucosa of the upper respiratory tract. Contact of styrene with epithelial cells stimulates the expression of a variety of inflammatory mediators, including the chemotactic cytokine monocyte chemoattractant protein-1 (MCP-1). To characterise the underlying mechanisms of the induction of inflammatory signals by styrene, we investigated the influence of this compound on the induction of oxidative stress and the activation of the nuclear factor-kappa B (NF-{kappa}B) signalling pathway in human lung epithelial cells (A549).more » The results demonstrate that styrene-induced MCP-1 expression, as well as the expression of the oxidative stress marker glutathione S-transferase (GST), is associated with a concentration dependent pattern of NF-{kappa}B activity. An inhibitor of NF-{kappa}B, IKK-NBD, and the anti-inflammatory antioxidant N-acetylcysteine (NAC) were both effective in suppressing styrene-induced MCP-1 secretion. In addition, NAC was capable of inhibiting the upregulation of GST expression. Our findings suggest that the activation of the NF-{kappa}B signalling pathway by styrene is mediated via a redox-sensitive mechanism.« less

  7. Moderate Resolution Spectroscopy of Substellar Companion Kappa Andromeda B

    NASA Astrophysics Data System (ADS)

    Wilcomb, Kielan; Konopacky, Quinn; Barman, Travis; Brown, Jessie; Brock, Laci; Macintosh, Bruce; Ruffio, Jean-Baptiste; Marois, Christian

    2018-01-01

    Recent direct imaging of exoplanets has revealed a population of Jupiter-like objects that orbit at large separations (~10-100 AU) from their host stars. These planets, with masses of ~2-14 MJup and temperatures of ~500-2000 K, remain a problem for the two main planet formation models—core accretion and gravitational instability. OSIRIS observations of directly imaged planets have expanded our understanding of their atmospheres, alluded to their formation, and uncovered individual molecular lines. Here, we present OSIRIS K band spectra of the “super-Jupiter,” Kappa Andromeda b. Kappa Andromeda b has a lower mass limit at the deuterium burning limit, but also has an uncertain age which may indicate the source is a higher mass brown dwarf. The spectra reveal resolved molecular lines from water and CO. We will present atmospheric properties of this object derived from comparison to PHOENIX atmosphere models, and measure a best fit C/O ratio for the source. We will compare our results to atmospheric properties of other brown dwarfs and gas giant planets in an effort to improve our knowledge of intricate atmospheres of young, substellar objects.

  8. Spacecraft observations of a Maxwell Demon coating the separatrix of asymmetric magnetic reconnection with crescent-shaped electron distributions

    NASA Astrophysics Data System (ADS)

    Egedal, J.; Le, A.; Daughton, W.; Wetherton, B.; Cassak, Pa; Chen, Lj; Lavraud, B.; Dorell, J.; Avanov, L.; Gershman, D.

    2016-10-01

    During asymmetric magnetic reconnection in the dayside magnetopause in situ spacecraft mea- surements show that electrons from the high density inflow penetrate some distance into the low density inflow. Supported by a kinetic simulation, we present a general derivation of an exclusion energy parameter, which provides a lower kinetic energy bound for an electron to jump across the reconnection region from one inflow region to the other. As by a Maxwell Demon, only high energy electrons are permitted to cross the inner reconnection region, strongly impacting the form of the electron distribution function observed along the low density side separatrix. The dynamics produce two distinct flavors of crescent-shaped electron distributions in a thin boundary layer along the separatrix between the magnetospheric inflow and the reconnection exhaust. The analytical model presented relates these salient details of the distribution function to the electron dynamics in the inner reconnection region.

  9. Inhibition of NF-kappaB-mediated transcription and induction of apoptosis in human breast cancer cells by epoxypseudoisoeugenol-2-methyl butyrate.

    PubMed

    Ma, Guoyi; Tabanca, Nurhayat; Husnu Can Baser, K; Kirimer, Nese; Pasco, David S; Khan, Ikhlas A; Khan, Shabana I

    2009-03-01

    Breast cancer is one of the most prevalent woman cancers. Genomic instability, accumulative mutations, and subsequent changes in intracellular signaling cascades play key roles in the development of human breast cancers. Activation of nuclear factor-kappaB (NF-kappaB) has been implicated in oncogenesis of breast cancers and is known to be associated with resistance to anticancer agents and apoptosis. Blocking NF-kappaB signaling may represent a therapeutic strategy in breast cancer therapy. The objective of this study is to investigate the in vitro effects of epoxypseudoisoeugenol-2-methyl butyrate (EPB), a phenylpropranoid isolated from Pimpinella corymbosa, on the activation of NF-kappaB, cell growth, cell cycle progression and apoptosis in MCF-7 (estrogen-dependent) and BT-549 (estrogen-independent) breast cancer cells. Transcriptional activity of NF-kappaB was measured by cell based reporter gene assay. Cell proliferation was determined by MTT assay. Cell cycle analysis was carried out by flow cytometry and apoptosis was observed by DAPI staining assy. EPB inhibited the NF-kappaB-mediated transcription activity induced by tumor necrosis factor-alpha (TNF-alpha) and phorbol myristate acetate (PMA) in MCF-7 cells. EPB also inhibited constitutive NF-kappaB transcriptional activity in BT-549 cells. EPB inhibited the proliferation of both MCF-7 and BT-549 cells in a concentration- and time-dependent manner. EPB induced cell cycle arrest in G(1)/G(0) phase and apoptosis in both MCF-7 and BT 549 cells. These in vitro results indicated that EPB has a potential for use against both hormone-dependent and hormone-independent breast cancers and its effects seem to be mediated by inhibiting the NF-kappaB activity.

  10. Evidence for nucleotide receptor modulation of cross talk between MAP kinase and NF-kappa B signaling pathways in murine RAW 264.7 macrophages.

    PubMed

    Aga, Mini; Watters, Jyoti J; Pfeiffer, Zachary A; Wiepz, Gregory J; Sommer, Julie A; Bertics, Paul J

    2004-04-01

    Extracellular nucleotides such as ATP are present in abundance at sites of inflammation and tissue damage, and these agents exert a potent modulatory effect on macrophage/monocyte function via the nucleotide receptor P2X(7). In this regard, after exposure to bacterial LPS, P2X(7) activation augments expression of the inducible nitric oxide (NO) synthase and production of NO in macrophages. Because P2X(7) has been reported to stimulate certain members of the MAP kinase family (ERK1/2) and can enhance the DNA-binding activity of NF-kappa B, we tested the hypothesis that LPS and nucleotides regulate NF-kappa B-dependent inflammatory events via cross talk with MAPK-associated pathways. In this regard, the present studies revealed that cotreatment of macrophages with LPS and the P2X(7)-selective ligand 2'-3'-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate (BzATP) results in the cooperative activation of NF-kappa B DNA-binding activity and a sustained attenuation of levels of the NF-kappa B inhibitory protein I kappa B alpha. Interestingly, a persistent reduction in I kappa B alpha levels is also observed when the MEK1/2 inhibitor U0126 is coadministered with LPS, suggesting that components of the MEK/ERK pathway are involved in regulating I kappa B alpha protein expression and/or turnover. The observation that U0126 and BzATP exhibit overlapping actions with respect to LPS-induced changes in I kappa B alpha levels is supported by the finding that Ras activation, which is upstream of MEK/ERK activation, is reduced upon macrophage cotreatment with BzATP and LPS compared with the effects of BzATP treatment alone. These data are consistent with the concept that the Ras/MEK/ERK pathways are involved in regulating NF-kappa B/I kappa B-dependent inflammatory mediator production and suggest a previously unidentified mechanism by which nucleotides can modulate LPS-induced action via cross talk between NF-kappa B and Ras/MEK/MAPK-associated pathways.

  11. Kapton charging characteristics: Effects of material thickness and electron-energy distribution

    NASA Technical Reports Server (NTRS)

    Williamson, W. S.; Dulgeroff, C. R.; Hymann, J.; Viswanathan, R.

    1985-01-01

    Charging characteristics of polyimide (Kapton) of varying thicknesses under irradiation by a very-low-curent-density electron beam, with the back surface of the sample grounded are reported. These charging characteristics are in good agreement with a simple analytical model which predicts that in thin samples at low current density, sample surface potential is limited by conduction leakage through the bulk material. The charging of Kapton in a low-current-density electron beam in which the beam energy was modulated to simulate Maxwellian and biMaxwellian distribution functions is measured.

  12. QUIET-TIME SUPRATHERMAL (∼0.1–1.5 keV) ELECTRONS IN THE SOLAR WIND

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tao, Jiawei; Wang, Linghua; Zong, Qiugang

    2016-03-20

    We present a statistical survey of the energy spectrum of solar wind suprathermal (∼0.1–1.5 keV) electrons measured by the WIND 3DP instrument at 1 AU during quiet times at the minimum and maximum of solar cycles 23 and 24. After separating (beaming) strahl electrons from (isotropic) halo electrons according to their different behaviors in the angular distribution, we fit the observed energy spectrum of both strahl and halo electrons at ∼0.1–1.5 keV to a Kappa distribution function with an index κ and effective temperature T{sub eff}. We also calculate the number density n and average energy E{sub avg} of strahl andmore » halo electrons by integrating the electron measurements between ∼0.1 and 1.5 keV. We find a strong positive correlation between κ and T{sub eff} for both strahl and halo electrons, and a strong positive correlation between the strahl n and halo n, likely reflecting the nature of the generation of these suprathermal electrons. In both solar cycles, κ is larger at solar minimum than at solar maximum for both strahl and halo electrons. The halo κ is generally smaller than the strahl κ (except during the solar minimum of cycle 23). The strahl n is larger at solar maximum, but the halo n shows no difference between solar minimum and maximum. Both the strahl n and halo n have no clear association with the solar wind core population, but the density ratio between the strahl and halo roughly anti-correlates (correlates) with the solar wind density (velocity)« less

  13. Molecular basis for the unique deubiquitinating activity of the NF-kappaB inhibitor A20.

    PubMed

    Lin, Su-Chang; Chung, Jee Y; Lamothe, Betty; Rajashankar, Kanagalaghatta; Lu, Miao; Lo, Yu-Chih; Lam, Amy Y; Darnay, Bryant G; Wu, Hao

    2008-02-15

    Nuclear factor kappaB (NF-kappaB) activation in tumor necrosis factor, interleukin-1, and Toll-like receptor pathways requires Lys63-linked nondegradative polyubiquitination. A20 is a specific feedback inhibitor of NF-kappaB activation in these pathways that possesses dual ubiquitin-editing functions. While the N-terminal domain of A20 is a deubiquitinating enzyme (DUB) for Lys63-linked polyubiquitinated signaling mediators such as TRAF6 and RIP, its C-terminal domain is a ubiquitin ligase (E3) for Lys48-linked degradative polyubiquitination of the same substrates. To elucidate the molecular basis for the DUB activity of A20, we determined its crystal structure and performed a series of biochemical and cell biological studies. The structure reveals the potential catalytic mechanism of A20, which may be significantly different from papain-like cysteine proteases. Ubiquitin can be docked onto a conserved A20 surface; this interaction exhibits charge complementarity and no steric clash. Surprisingly, A20 does not have specificity for Lys63-linked polyubiquitin chains. Instead, it effectively removes Lys63-linked polyubiquitin chains from TRAF6 without dissembling the chains themselves. Our studies suggest that A20 does not act as a general DUB but has the specificity for particular polyubiquitinated substrates to assure its fidelity in regulating NF-kappaB activation in the tumor necrosis factor, interleukin-1, and Toll-like receptor pathways.

  14. Effects of anisotropic electron-ion interactions in atomic photoelectron angular distributions

    NASA Technical Reports Server (NTRS)

    Dill, D.; Starace, A. F.; Manson, S. T.

    1975-01-01

    A summary of the angular momentum transfer formulation of the differential photoionization cross section is presented and photoionization amplitudes in LS coupling are considered. The application of the theoretical concepts and relations developed is illustrated with the aid of an example involving the calculation of the angular distribution of photoelectrons ionized from atomic sulfur according to a certain reaction. The investigation shows that anisotropic electron-ion interactions in atomic sulfur lead to measurable differences between photoelectron angular distribution asymmetry parameters corresponding to alternative ionic term levels.

  15. TRAF2-binding BIR1 domain of c-IAP2/MALT1 fusion protein is essential for activation of NF-kappaB.

    PubMed

    Garrison, J B; Samuel, T; Reed, J C

    2009-04-02

    Marginal zone mucosa-associated lymphoid tissue (MALT) B-cell lymphoma is the most common extranodal non-Hodgkin lymphoma. The t(11;18)(q21;q21) translocation occurs frequently in MALT lymphomas and creates a chimeric NF-kappaB-activating protein containing the baculoviral IAP repeat (BIR) domains of c-IAP2 (inhibitor of apoptosis protein 2) fused with portions of the MALT1 protein. The BIR1 domain of c-IAP2 interacts directly with TRAF2 (TNFalpha-receptor-associated factor-2), but its role in NF-kappaB activation is still unclear. Here, we investigated the role of TRAF2 in c-IAP2/MALT1-induced NF-kappaB activation. We show the BIR1 domain of c-IAP2 is essential for NF-kappaB activation, whereas BIR2 and BIR3 domains are not. Studies of c-IAP2/MALT1 BIR1 mutant (E47A/R48A) that fails to activate NF-kappaB showed loss of TRAF2 binding, but retention of TRAF6 binding, suggesting that interaction of c-IAP2/MALT1 with TRAF6 is insufficient for NF-kappaB induction. In addition, a dominant-negative TRAF2 mutant or downregulation of TRAF2 achieved by small interfering RNA inhibited NF-kappaB activation by c-IAP2/MALT1 showing that TRAF2 is indispensable. Comparisons of the bioactivity of intact c-IAP2/MALT1 oncoprotein and BIR1 E47A/R48A c-IAP2/MALT1 mutant that cannot bind TRAF2 in a lymphoid cell line provided evidence that TRAF2 interaction is critical for c-IAP2/MALT1-mediated increases in the NF-kappaB activity, increased expression of endogenous NF-kappaB target genes (c-FLIP, TRAF1), and resistance to apoptosis.

  16. Spectral characteristics of plasma sheet ion and electron populations during disturbed geomagnetic conditions

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Christon, S.P., Williams, D.J.; Mitchell, D.G.; Huang, C.Y.

    1991-01-01

    The authors have determined the spectral characteristics of central plasma sheet ions and electrons observed during 71 hours when geomagnetic activity was at moderate to high levels (AE {ge} 100nT). Particle data from the low-energy proton and electron differential energy analyzer and the medium energy particle instrument on ISEE 1 are combined to obtain differential energy spectra (measured in units of particles/cm{sup 2} s sr keV) in the kinetic energy range {approximately}30 eV/e to {approximately}1 MeV at geocentric radial distances >12R{sub e}. Nearly isotropic central plasma sheet total ion and electron populations were chosen for analysis and were measured tomore » be continuous particle distributions from the lowest to highest energies. During these high AE periods the >24 keV particle fluxes and the temperature of the entire particle distribution kT are significantly higher than during low AE periods (AE < 100 nT). The temperatures kT{sub i} and kT{sub e} are highly correlated during both quiet and disturbed periods. The active period spectral shape appears softer for ions and somewhat harder for electrons than during quiet periods. They find that the observed active period spectrum typically is complex and cannot be represented in general by a single functional form, as during quiet periods when it can be represented by the kappa distribution function. In a limited energy range near the knee of the ion spectra, the spectral shape can often be fit with a Maxwellian form, thus rolling over faster than the typical quiet time spectrum. Electron spectra also display this spectral characteristic, although at a lower occurence frequency than for ions. The electron spectra are predominantly kappalike at energies near and above the knee. The authors conclude that both ions and electrons participate in at least two separate accerlation mechanisms as geomagnetic activity evolves from low AE to high AE values.« less

  17. SIRT1 overexpression decreases cisplatin-induced acetylation of NF-{kappa}B p65 subunit and cytotoxicity in renal proximal tubule cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jung, Yu Jin; Lee, Jung Eun; Lee, Ae Sin

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer Cisplatin increases acetylation of NF-{kappa}B p65 subunit in HK2 cells. Black-Right-Pointing-Pointer SIRT1 overexpression decreases cisplatin-induced p65 acetylation and -cytotoxicity. Black-Right-Pointing-Pointer Resveratrol decreased cisplatin-induced cell viability through deacetylation of p65. -- Abstract: As the increased acetylation of p65 is linked to nuclear factor-{kappa}B (NF-{kappa}B) activation, the regulation of p65 acetylation can be a potential target for the treatment of inflammatory injury. Cisplatin-induced nephrotoxicity is an important issue in chemotherapy of cancer patients. SIRT1, nicotinamide adenine dinucleotide (NAD{sup +})-dependent protein deacetylase, has been implicated in a variety of cellular processes such as inflammatory injury and the control of multidrug resistancemore » in cancer. However, there is no report on the effect of SIRT1 overexpression on cisplatin-induced acetylation of p65 subunit of NF-{kappa}B and cell injury. To investigate the effect of SIRT1 in on cisplatin-induced acetylation of p65 subunit of NF-{kappa}B and cell injury, HK2 cells were exposed with SIRT1 overexpression, LacZ adenovirus or dominant negative adenovirus after treatment with cisplatin. While protein expression of SIRT1 was decreased by cisplatin treatment compared with control buffer treatment, acetylation of NF-{kappa}B p65 subunit was significantly increased after treatment with cisplatin. Overexpression of SIRT1 ameliorated the increased acetylation of p65 of NF-{kappa}B during cisplatin treatment and cisplatin-induced cytotoxicity. Further, treatment of cisplatin-treated HK2 cells with resveratrol, a SIRT1 activator, also decreased acetylation of NF-{kappa}B p65 subunit and cisplatin-induced increase of the cell viability in HK2 cells. Our findings suggests that the regulation of acetylation of p65 of NF-{kappa}B through SIRT1 can be a possible target to attenuate cisplatin-induced renal cell damage.« less

  18. A method for atomic-level noncontact thermometry with electron energy distribution

    NASA Astrophysics Data System (ADS)

    Kinoshita, Ikuo; Tsukada, Chiharu; Ouchi, Kohei; Kobayashi, Eiichi; Ishii, Juntaro

    2017-04-01

    We devised a new method of determining the temperatures of materials with their electron-energy distributions. The Fermi-Dirac distribution convoluted with a linear combination of Gaussian and Lorentzian distributions was fitted to the photoelectron spectrum measured for the Au(110) single-crystal surface at liquid N2-cooled temperature. The fitting successfully determined the surface-local thermodynamic temperature and the energy resolution simultaneously from the photoelectron spectrum, without any preliminary results of other measurements. The determined thermodynamic temperature was 99 ± 2.1 K, which was in good agreement with the reference temperature of 98.5 ± 0.5 K measured using a silicon diode sensor attached to the sample holder.

  19. Behavioral meaningful opioidergic stimulation activates kappa receptor gene expression

    PubMed Central

    Teodorov, E.; Ferrari, M.F.R.; Fior-Chadi, D.R.; Camarini, R.; Felício, L.F.

    2012-01-01

    The periaqueductal gray (PAG) has been reported to be a location for opioid regulation of pain and a potential site for behavioral selection in females. Opioid-mediated behavioral and physiological responses differ according to the activity of opioid receptor subtypes. The present study investigated the effects of the peripheral injection of the kappa-opioid receptor agonist U69593 into the dorsal subcutaneous region of animals on maternal behavior and on Oprk1 gene activity in the PAG of female rats. Female Wistar rats weighing 200-250 g at the beginning of the study were randomly divided into 2 groups for maternal behavior and gene expression experiments. On day 5, pups were removed at 7:00 am and placed in another home cage that was distant from their mother. Thirty minutes after removing the pups, the dams were treated with U69593 (0.15 mg/kg, sc) or 0.9% saline (up to 1 mL/kg) and after 30 min were evaluated in the maternal behavior test. Latencies in seconds for pup retrieval, grouping, crouching, and full maternal behavior were scored. The results showed that U69593 administration inhibited maternal behavior (P < 0.05) because a lower percentage of U69593 group dams showed retrieval of first pup, retrieving all pups, grouping, crouching and displaying full maternal behavior compared to the saline group. Opioid gene expression was evaluated using real-time reverse-transcription polymerase chain reaction (RT-PCR). A single injection of U69593 increased Oprk1 PAG expression in both virgin (P < 0.05) and lactating female rats (P < 0.01), with no significant effect on Oprm1 or Oprd1 gene activity. Thus, the expression of kappa-opioid receptors in the PAG may be modulated by single opioid receptor stimulation and behavioral meaningful opioidergic transmission in the adult female might occur simultaneously to specific changes in gene expression of kappa-opioid receptor subtype. This is yet another alert for the complex role of the opioid system in female

  20. Temporal patterns of mental model convergence: implications for distributed teams interacting in electronic collaboration spaces.

    PubMed

    McComb, Sara; Kennedy, Deanna; Perryman, Rebecca; Warner, Norman; Letsky, Michael

    2010-04-01

    Our objective is to capture temporal patterns in mental model convergence processes and differences in these patterns between distributed teams using an electronic collaboration space and face-to-face teams with no interface. Distributed teams, as sociotechnical systems, collaborate via technology to work on their task. The way in which they process information to inform their mental models may be examined via team communication and may unfold differently than it does in face-to-face teams. We conducted our analysis on 32 three-member teams working on a planning task. Half of the teams worked as distributed teams in an electronic collaboration space, and the other half worked face-to-face without an interface. Using event history analysis, we found temporal interdependencies among the initial convergence points of the multiple mental models we examined. Furthermore, the timing of mental model convergence and the onset of task work discussions were related to team performance. Differences existed in the temporal patterns of convergence and task work discussions across conditions. Distributed teams interacting via an electronic interface and face-to-face teams with no interface converged on multiple mental models, but their communication patterns differed. In particular, distributed teams with an electronic interface required less overall communication, converged on all mental models later in their life cycles, and exhibited more linear cognitive processes than did face-to-face teams interacting verbally. Managers need unique strategies for facilitating communication and mental model convergence depending on teams' degrees of collocation and access to an interface, which in turn will enhance team performance.

  1. Monte Carlo N Particle code - Dose distribution of clinical electron beams in inhomogeneous phantoms

    PubMed Central

    Nedaie, H. A.; Mosleh-Shirazi, M. A.; Allahverdi, M.

    2013-01-01

    Electron dose distributions calculated using the currently available analytical methods can be associated with large uncertainties. The Monte Carlo method is the most accurate method for dose calculation in electron beams. Most of the clinical electron beam simulation studies have been performed using non- MCNP [Monte Carlo N Particle] codes. Given the differences between Monte Carlo codes, this work aims to evaluate the accuracy of MCNP4C-simulated electron dose distributions in a homogenous phantom and around inhomogeneities. Different types of phantoms ranging in complexity were used; namely, a homogeneous water phantom and phantoms made of polymethyl methacrylate slabs containing different-sized, low- and high-density inserts of heterogeneous materials. Electron beams with 8 and 15 MeV nominal energy generated by an Elekta Synergy linear accelerator were investigated. Measurements were performed for a 10 cm × 10 cm applicator at a source-to-surface distance of 100 cm. Individual parts of the beam-defining system were introduced into the simulation one at a time in order to show their effect on depth doses. In contrast to the first scattering foil, the secondary scattering foil, X and Y jaws and applicator provide up to 5% of the dose. A 2%/2 mm agreement between MCNP and measurements was found in the homogenous phantom, and in the presence of heterogeneities in the range of 1-3%, being generally within 2% of the measurements for both energies in a "complex" phantom. A full-component simulation is necessary in order to obtain a realistic model of the beam. The MCNP4C results agree well with the measured electron dose distributions. PMID:23533162

  2. Pulsar distances and the galactic distribution of free electrons

    NASA Technical Reports Server (NTRS)

    Taylor, J. H.; Cordes, J. M.

    1993-01-01

    The present quantitative model for Galactic free electron distribution abandons the assumption of axisymmetry and explicitly incorporates spiral arms; their shapes and locations are derived from existing radio and optical observations of H II regions. The Gum Nebula's dispersion-measure contributions are also explicitly modeled. Adjustable quantities are calibrated by reference to three different types of data. The new model is estimated to furnish distance estimates to known pulsars that are accurate to about 25 percent.

  3. Human immunodeficiency virus type 1 Nef protein inhibits NF-kappa B induction in human T cells.

    PubMed Central

    Niederman, T M; Garcia, J V; Hastings, W R; Luria, S; Ratner, L

    1992-01-01

    Human immunodeficiency virus type 1 (HIV-1) can establish a persistent and latent infection in CD4+ T lymphocytes (W. C. Greene, N. Engl. J. Med. 324:308-317, 1991; S. M. Schnittman, M. C. Psallidopoulos, H. C. Lane, L. Thompson, M. Baseler, F. Massari, C. H. Fox, N. P. Salzman, and A. S. Fauci, Science 245:305-308, 1989). Production of HIV-1 from latently infected cells requires host cell activation by T-cell mitogens (T. Folks, D. M. Powell, M. M. Lightfoote, S. Benn, M. A. Martin, and A. S. Fauci, Science 231:600-602, 1986; D. Zagury, J. Bernard, R. Leonard, R. Cheynier, M. Feldman, P. S. Sarin, and R. C. Gallo, Science 231:850-853, 1986). This activation is mediated by the host transcription factor NF-kappa B [G. Nabel and D. Baltimore, Nature (London) 326:711-717, 1987]. We report here that the HIV-1-encoded Nef protein inhibits the induction of NF-kappa B DNA-binding activity by T-cell mitogens. However, Nef does not affect the DNA-binding activity of other transcription factors implicated in HIV-1 regulation, including SP-1, USF, URS, and NF-AT. Additionally, Nef inhibits the induction of HIV-1- and interleukin 2-directed gene expression, and the effect on HIV-1 transcription depends on an intact NF-kappa B-binding site. These results indicate that defective recruitment of NF-kappa B may underlie Nef's negative transcriptional effects on the HIV-1 and interleukin 2 promoters. Further evidence suggests that Nef inhibits NF-kappa B induction by interfering with a signal derived from the T-cell receptor complex. Images PMID:1527859

  4. High-frequency expression of a conserved kappa light-chain variable-region gene in chronic lymphocytic leukemia

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kipps, T.J.; Fong, S.; Tomhave, E.

    Malignant B lymphocytes from several patients with chronic lymphocytic leukemia (CLL) were examined for reactivity with murine monoclonal antibody 17.109. This antibody, prepared against the rheumatoid factor (RF) paraprotein Sie, recognizes a cross reactive idiotype on 48% of human IgM RF paraproteins, but does not react with IgM paraproteins without RF activity or substantially with normal pooled immunoglobulin. The 17.109-reactive idiotype is a marker for a kappa III variable-region gene, designated V/sub kappa/RF, that is conserved in outbred human populations. In a limited study of 31 CLL patients, the leukemic cells from 5 of 20 patients with kappa light chain-expressingmore » CLL were recognized by the 17.109 monoclonal antibody. Despite having malignant cells specifically reactive with this antibody, patients with 17.109-positive CLL did not have elevated serum levels of circulating antibody bearing 17.109-reactive determinants. Total RNAs isolated from the CLL B lymphocytes, or from hybridomas produced by fusing the CLL cells with the WI-L2-729-HF/sub 2/ cell line, were fractionated electrophoretically and examined by blot hybridization. Under stringent hybridization conditions capable of discerning a single base-pair mismatch, RNA from the 17.109-idiotype-positive CLL cells hybridized to synthetic oligonucleotide probes corresponding to framework and complementary-determining regions in the V/sub kappa/RF gene. The high frequency of the 17.109-associated idiotype and the V/sub kappa/RF gene in CLL suggests that the disease may arise from B lymphocytes that express a restricted set of inherited immunoglobulin variable-region genes with little or no somatic mutation.« less

  5. Angular distributions of absorbed dose of Bremsstrahlung and secondary electrons induced by 18-, 28- and 38-MeV electron beams in thick targets.

    PubMed

    Takada, Masashi; Kosako, Kazuaki; Oishi, Koji; Nakamura, Takashi; Sato, Kouichi; Kamiyama, Takashi; Kiyanagi, Yoshiaki

    2013-03-01

    Angular distributions of absorbed dose of Bremsstrahlung photons and secondary electrons at a wide range of emission angles from 0 to 135°, were experimentally obtained using an ion chamber with a 0.6 cm(3) air volume covered with or without a build-up cap. The Bremsstrahlung photons and electrons were produced by 18-, 28- and 38-MeV electron beams bombarding tungsten, copper, aluminium and carbon targets. The absorbed doses were also calculated from simulated photon and electron energy spectra by multiplying simulated response functions of the ion chambers, simulated with the MCNPX code. Calculated-to-experimental (C/E) dose ratios obtained are from 0.70 to 1.57 for high-Z targets of W and Cu, from 15 to 135° and the C/E range from 0.6 to 1.4 at 0°; however, the values of C/E for low-Z targets of Al and C are from 0.5 to 1.8 from 0 to 135°. Angular distributions at the forward angles decrease with increasing angles; on the other hand, the angular distributions at the backward angles depend on the target species. The dependences of absorbed doses on electron energy and target thickness were compared between the measured and simulated results. The attenuation profiles of absorbed doses of Bremsstrahlung beams at 0, 30 and 135° were also measured.

  6. The main types of electron energy distribution determined by model fitting to optical emissions during HF wave ionospheric modification experiments

    NASA Astrophysics Data System (ADS)

    Vlasov, M. N.; Kelley, M. C.; Hysell, D. L.

    2013-06-01

    Enhanced optical emissions observed during HF pumping are induced by electrons accelerated by high-power electromagnetic waves. Using measured emission intensities, the energy distribution of accelerated electrons can be inferred. Energy loss from the excitation of molecular nitrogen vibrational levels (the vibrational barrier) strongly influences the electron energy distribution (EED). In airglow calculations, compensation for electron depletion within the 2-3 eV energy range, induced by the vibrational barrier, can be achieved via electrons with an EED similar to a Gaussian distribution and energies higher than 3 eV. This EED has a peak within the 5-10 eV energy range. We show that the main EED features depend strongly on altitude and solar activity. An EED similar to a power law distribution can occur above 270-300 km altitude. Below 270 km altitude, a Gaussian distribution for energies between 3 eV and 10 eV, together with a power law distribution for energies higher than 10 eV, is indicated. A Gaussian distribution combined with an exponential function is needed below 230 km altitude. The transition altitude from Gaussian to power law distribution depends strongly on solar activity, increasing for high solar activity. Electrons accelerated during the initial collisionless stage can inhibit the depletion of fast electrons within the vibrational barrier range, an effect that strongly depends on altitude and solar activity. The approach, based on the effective root square electric field, enables EED calculation, providing the observed red-line intensities for low and high solar activities.

  7. [The reconstruction of welding arc 3D electron density distribution based on Stark broadening].

    PubMed

    Zhang, Wang; Hua, Xue-Ming; Pan, Cheng-Gang; Li, Fang; Wang, Min

    2012-10-01

    The three-dimensional electron density is very important for welding arc quality control. In the present paper, Side-on characteristic line profile was collected by a spectrometer, and the lateral experimental data were approximated by a polynomial fitting. By applying an Abel inversion technique, the authors obtained the radial intensity distribution at each wavelength and thus constructed a profile for the radial positions. The Fourier transform was used to separate the Lorentz linear from the spectrum reconstructed, thus got the accurate Stark width. And we calculated the electronic density three-dimensional distribution of the TIG welding are plasma.

  8. Elimination of endogenous aberrant kappa chain transcripts from sp2/0-derived hybridoma cells by specific ribozyme cleavage: utility in genetic therapy of HIV-1 infections.

    PubMed Central

    Duan, L; Pomerantz, R J

    1994-01-01

    The pooled degenerate-primer polymerase chain reaction (PCR) technology is now widely used in the amplification and cloning of murine hybridoma-specific immunoglobulin gene cDNAs. The design of primers is mainly based on the highly conserved 5' terminus of immunoglobulin gene variable regions and the constant region in the 3' terminus. Of note, most murine hybridoma cell lines are derived from the Sp2/0 cell line, which is demonstrated to express endogenous aberrant kappa chains (abV kappa). This high-level endogenous abV kappa mixes with specific kappa chains in the hybridomas and interferes with the efficiency of the reverse transcriptase (RT)-PCR cloning strategy. In this report, during the cloning of murine anti-human immunodeficiency virus type I (HIV-1) hybridoma immunoglobulin cDNAs, a specific primer-PCR screening system was developed, based on the abV kappa complementarity-defining region (CDR), to eliminate abV kappa-carrying plasmids. Furthermore, an abV kappa sequence-specific derived ribozyme was developed and packaged in a retroviral expression vector system. This abV kappa ribozyme can be transduced into different murine hybridomas, and expressed intracellularly to potently eliminate endogenous abV kappa RNA. Images PMID:7816635

  9. Tumour Necrosis Factor-alpha and Nuclear Factor-kappa B Gene Variants in Sepsis.

    PubMed

    Acar, Leyla; Atalan, Nazan; Karagedik, E Hande; Ergen, Arzu

    2018-01-20

    The humoral system is activated and various cytokines are released due to infections in tissues and traumatic damage. Nuclear factor-kappa B dimers are encoded by nuclear factor-kappa B genes and regulate transcription of several crucial proteins of inflammation such as tumour necrosis factor-alpha. To investigate the possible effect of polymorphisms on tumour necrosis factor-alpha serum levels with clinical and prognostic parameters of sepsis by determining the nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A) gene polymorphisms and tumour necrosis factor-alpha serum levels. Case-control study. Seventy-two patients with sepsis and 104 healthy controls were included in the study. In order to determine the polymorphisms of nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A), polymerase chain reaction-restriction fragment length polymorphism analysis was performed and serum tumour necrosis factor-alpha levels were determined using an enzyme-linked immunosorbent assay. We observed no significant differences in tumour necrosis factor-alpha serum levels between the study groups. In the patient group, an increase in the tumour necrosis factor-alpha serum levels in patients carrying the tumour necrosis factor-alpha (-308 G/A) A allele compared to those without the A allele was found to be statistically significant. Additionally, an increase in the tumour necrosis factor-alpha serum levels in patients carrying tumour necrosis factor-alpha (-308 G/A) AA genotype compared with patients carrying the AG or GG genotypes was statistically significant. No significant differences were found in these 2 polymorphisms between the patient and control groups (p>0.05). Our results showed the AA genotype and the A allele of the tumour necrosis factor-alpha (-308 G/A) polymorphism may be used as a predictor of elevated tumour necrosis factor-alpha levels in patients with sepsis.

  10. Time-dependent modulation of thioredoxin reductase activity might contribute to sulforaphane-mediated inhibition of NF-kappaB binding to DNA.

    PubMed

    Heiss, Elke; Gerhäuser, Clarissa

    2005-01-01

    The chemopreventive agent sulforaphane (SFN) exerts anti-inflammatory activity by thiol-dependent inhibition of nuclear factor kappaB (NF-kappaB) DNA binding. To further analyze the underlying mechanisms, we focused on the thioredoxin/thioredoxin reductase (TrxR) system as a key redox mechanism regulating NF-kappaB DNA binding. Using cultured Raw 264.7 mouse macrophages as a model, 1-chloro-2,4-dinitrobenzene (CDNB), a known inhibitor of TrxR, was identified as an inhibitor of lipopolysaccharide (LPS)-mediated nitric oxide (NO) production and of NF-kappaB DNA binding. CDNB and SFN acted synergistically with respect to inhibition of LPS-induced NO release, and we consequently identified SFN as a novel inhibitor of TrxR enzymatic activity in vitro. Short-term treatment of Raw macrophages with SFN or CDNB resulted in the inhibition of TrxR activity in vivo with half-maximal inhibitory concentration of 25.0 +/- 3.5 microM and 9.4 +/- 3.7 microM, respectively, whereas after a 24-h treatment with 25 microM SFN, TrxR activity was >1.5-fold elevated. In additional experiments, we could exclude that inhibition of trans-activating activity of NF-kappaB contributed to the reduced expression of pro-inflammatory proteins by SFN, based on transient transfection experiments with a (kappaB)(2)- chloramphenicol acetyltransferase construct and a lack of inhibition of protein kinase A activity. These findings further emphasize the importance of redox modulation or thiol reactivity for the regulation of NF-kappaB-dependent transcription by SFN. Antioxid. Redox Signal. 7, 1601-1611. Antioxid. Redox Signal. 7, 1601-1611.

  11. Novel pharmacology: asimadoline, a kappa-opioid agonist, and visceral sensation.

    PubMed

    Camilleri, M

    2008-09-01

    Asimadoline is a potent kappa-opioid receptor agonist with a diaryl acetamide structure. It has high affinity for the kappa receptor, with IC(50) of 5.6 nmol L(-1) (guinea pig) and 1.2 nmol L(-1) (human recombinant), and high selectively with kappa : micro : delta binding ratios of 1 : 501 : 498 in human recombinant receptors. It acts as a complete agonist in in vitro assay. Asimadoline reduced sensation in response to colonic distension at subnoxious pressures in healthy volunteers and in irritable bowel syndrome (IBS) patients without alteration of colonic compliance. Asimadoline reduced satiation and enhanced the postprandial gastric volume (in female volunteers). However, there were no significant effects on gastrointestinal transit, colonic compliance, fasting or postprandial colonic tone. In a clinical trial in 40 patients with functional dyspepsia (Rome II), asimadoline did not significantly alter satiation or symptoms over 8 weeks. However, asimadoline, 0.5 mg, significantly decreased satiation in patients with higher postprandial fullness scores, and daily postprandial fullness severity (over 8 weeks); the asimadoline 1.0 mg group was borderline significant. In a clinical trial in patients with IBS, average pain 2 h post-on-demand treatment with asimadoline was not significantly reduced. Post hoc analyses suggest that asimadoline was effective in mixed IBS. In a 12-week study in 596 patients, chronic treatment with 0.5 mg and 1.0 mg asimadoline was associated with adequate relief of pain and discomfort, improvement in pain score and number of pain-free days in patients with IBS-D. The 1.0 mg dose was also efficacious in IBS-alternating. There were also weeks with significant reduction in bowel frequency and urgency. Asimadoline has been well tolerated in human trials to date.

  12. Three-dimensional analytical model for the spatial variation of the foreshock electron distribution function - Systematics and comparisons with ISEE observations

    NASA Technical Reports Server (NTRS)

    Fitzenreiter, R. J.; Scudder, J. D.; Klimas, A. J.

    1990-01-01

    A model which is consistent with the solar wind and shock surface boundary conditions for the foreshock electron distribution in the absence of wave-particle effects is formulated for an arbitrary location behind the magnetic tangent to the earth's bow shock. Variations of the gyrophase-averaged velocity distribution are compared and contrasted with in situ ISEE observations. It is found that magnetic mirroring of solar wind electrons is the most important process by which nonmonotonic reduced electron distributions in the foreshock are produced. Leakage of particles from the magnetosheath is shown to be relatively unimportant in determining reduced distributions that are nonmonotonic. The two-dimensional distribution function off the magnetic field direction is the crucial contribution in producing reduced distributions which have beams. The time scale for modification of the electron velocity distribution in velocity space can be significantly influenced by steady state spatial gradients in the background imposed by the curved shock geometry.

  13. Myricetin down-regulates phorbol ester-induced cyclooxygenase-2 expression in mouse epidermal cells by blocking activation of nuclear factor kappa B.

    PubMed

    Lee, Kyung Mi; Kang, Nam Joo; Han, Jin Hee; Lee, Ki Won; Lee, Hyong Joo

    2007-11-14

    Abnormal expression of cyclooxygenase-2 (COX-2) has been implicated in the development of cancer. There are multiple lines of evidence that red wine exerts chemopreventive effects, and 3,5,4'-trihydroxy- trans-stilbene (resveratrol), which is a non-flavonoid polyphenol found in red wine, has been reported to be a natural chemopreventive agent. However, other phytochemicals might contribute to the cancer-preventive activities of red wine, and the flavonol content of red wines is about 30 times higher than that of resveratrol. Here we report that 3,3',4',5,5',7-hexahydroxyflavone (myricetin), one of the major flavonols in red wine, inhibits 12-O-tetradecanoylphorbol-13-acetate (phorbol ester)-induced COX-2 expression in JB6 P+ mouse epidermal (JB6 P+) cells by suppressing activation of nuclear factor kappa B (NF-kappaB). Myricetin at 10 and 20 microM inhibited phorbol ester-induced upregulation of COX-2 protein, while resveratrol at the same concentration did not exert significant effects. The phorbol ester-induced production of prostaglandin E 2 was also attenuated by myricetin treatment. Myricetin inhibited both COX-2 and NF-kappaB transactivation in phorbol ester-treated JB6 P+ cells, as determined using a luciferase assay. Myricetin blocked the phorbol ester-stimulated DNA binding activity of NF-kappaB, as determined using an electrophoretic mobility shift assay. Moreover, TPCK (N-tosyl-l-phenylalanine chloromethyl ketone), a NF-kappaB inhibitor, significantly attenuated COX-2 expression and NF-kappaB promoter activity in phorbol ester-treated JB6 P+ cells. In addition, red wine extract inhibited phorbol ester-induced COX-2 expression and NF-kappaB transactivation in JB6 P+ cells. Collectively, these data suggest that myricetin contributes to the chemopreventive effects of red wine through inhibition of COX-2 expression by blocking the activation of NF-kappaB.

  14. Effects of ketoprofen, morphine, and kappa opioids on pain-related depression of nesting in mice.

    PubMed

    Negus, S Stevens; Neddenriep, Bradley; Altarifi, Ahmad A; Carroll, F Ivy; Leitl, Michael D; Miller, Laurence L

    2015-06-01

    Pain-related functional impairment and behavioral depression are diagnostic indicators of pain and targets for its treatment. Nesting is an innate behavior in mice that may be sensitive to pain manipulations and responsive to analgesics. The goal of this study was to develop and validate a procedure for evaluation of pain-related depression of nesting in mice. Male ICR mice were individually housed and tested in their home cages. On test days, a 5- × 5-cm Nestlet was subdivided into 6 pieces, the pieces were evenly distributed on the cage floor, and Nestlet consolidation was quantified during 100-minute sessions. Baseline nesting was stable within and between subjects, and nesting was depressed by 2 commonly used inflammatory pain stimuli (intraperitoneal injection of dilute acid; intraplantar injection of complete Freund adjuvant). Pain-related depression of nesting was alleviated by drugs from 2 classes of clinically effective analgesics (the nonsteroidal anti-inflammatory drug ketoprofen and the μ-opioid receptor agonist morphine) but not by a drug from a class that has failed to yield effective analgesics (the centrally acting kappa opioid agonist U69,593). Neither ketoprofen nor morphine alleviated depression of nesting by U69,593, which suggests that ketoprofen and morphine effects were selective for pain-related depression of nesting. In contrast to ketoprofen and morphine, the kappa opioid receptor antagonist JDTic blocked depression of nesting by U69,593 but not by acid or complete Freund adjuvant. These results support utility of this procedure to assess expression and treatment of pain-related depression in mice.

  15. Total-scattering pair-distribution function of organic material from powder electron diffraction data

    DOE PAGES

    Gorelik, Tatiana E.; Billinge, Simon J. L.; Schmidt, Martin U.; ...

    2015-04-01

    This paper shows for the first time that pair-distribution function analyses can be carried out on organic and organo-metallic compounds from powder electron diffraction data. Different experimental setups are demonstrated, including selected area electron diffraction (SAED) and nanodiffraction in transmission electron microscopy (TEM) or nanodiffraction in scanning transmission electron microscopy (STEM) modes. The methods were demonstrated on organo-metallic complexes (chlorinated and unchlorinated copper-phthalocyanine) and on purely organic compounds (quinacridone). The PDF curves from powder electron diffraction data, called ePDF, are in good agreement with PDF curves determined from X-ray powder data demonstrating that the problems of obtaining kinematical scattering datamore » and avoiding beam-damage of the sample are possible to resolve.« less

  16. Modulation instability and dissipative rogue waves in ion-beam plasma: Roles of ionization, recombination, and electron attachment

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Guo, Shimin, E-mail: gsm861@126.com; Mei, Liquan, E-mail: lqmei@mail.xjtu.edu.cn

    The amplitude modulation of ion-acoustic waves is investigated in an unmagnetized plasma containing positive ions, negative ions, and electrons obeying a kappa-type distribution that is penetrated by a positive ion beam. By considering dissipative mechanisms, including ionization, negative-positive ion recombination, and electron attachment, we introduce a comprehensive model for the plasma with the effects of sources and sinks. Via reductive perturbation theory, the modified nonlinear Schrödinger equation with a dissipative term is derived to govern the dynamics of the modulated waves. The effect of the plasma parameters on the modulation instability criterion for the modified nonlinear Schrödinger equation is numericallymore » investigated in detail. Within the unstable region, first- and second-order dissipative ion-acoustic rogue waves are present. The effect of the plasma parameters on the characteristics of the dissipative rogue waves is also discussed.« less

  17. Distribution and dynamics of electron transport complexes in cyanobacterial thylakoid membranes.

    PubMed

    Liu, Lu-Ning

    2016-03-01

    The cyanobacterial thylakoid membrane represents a system that can carry out both oxygenic photosynthesis and respiration simultaneously. The organization, interactions and mobility of components of these two electron transport pathways are indispensable to the biosynthesis of thylakoid membrane modules and the optimization of bioenergetic electron flow in response to environmental changes. These are of fundamental importance to the metabolic robustness and plasticity of cyanobacteria. This review summarizes our current knowledge about the distribution and dynamics of electron transport components in cyanobacterial thylakoid membranes. Global understanding of the principles that govern the dynamic regulation of electron transport pathways in nature will provide a framework for the design and synthetic engineering of new bioenergetic machinery to improve photosynthesis and biofuel production. This article is part of a Special Issue entitled: Organization and dynamics of bioenergetic systems in bacteria, edited by Conrad Mullineaux. Copyright © 2015 The Author. Published by Elsevier B.V. All rights reserved.

  18. Gap length effect on electron energy distribution in capacitive radio frequency discharges

    NASA Astrophysics Data System (ADS)

    You, S. J.; Kim, S. S.; Kim, Jung-Hyung; Seong, Dae-Jin; Shin, Yong-Hyeon; Chang, H. Y.

    2007-11-01

    A study on the dependence of electron energy distribution function (EEDF) on discharge gap size in capacitive rf discharges was conducted. The evolution of the EEDF over a gap size range from 2.5to7cm in 65mTorr Ar discharges was investigated both experimentally and theoretically. The measured EEDFs exhibited typical bi-Maxwellian forms with low energy electron groups. A significant depletion in the low energy portion of the bi-Maxwellian was found with decreasing gap size. The results show that electron heating by bulk electric fields, which is the main heating process of the low-energy electrons, is greatly enhanced as the gap size decreases, resulting in the abrupt change of the EEDF. The calculated EEDFs based on nonlocal kinetic theory are in good agreement with the experiments.

  19. Measurement and dynamics of the spatial distribution of an electron localized at a metal-dielectric interface

    NASA Astrophysics Data System (ADS)

    Bezel, Ilya; Gaffney, Kelly J.; Garrett-Roe, Sean; Liu, Simon H.; Miller, André D.; Szymanski, Paul; Harris, Charles B.

    2004-01-01

    The ability of time- and angle-resolved two-photon photoemission to estimate the size distribution of electron localization in the plane of a metal-adsorbate interface is discussed. It is shown that the width of angular distribution of the photoelectric current is inversely proportional to the electron localization size within the most common approximations in the description of image potential states. The localization of the n=1 image potential state for two monolayers of butyronitrile on Ag(111) is used as an example. For the delocalized n=1 state, the shape of the signal amplitude as a function of momentum parallel to the surface changes rapidly with time, indicating efficient intraband relaxation on a 100 fs time scale. For the localized state, little change was observed. The latter is related to the constant size distribution of electron localization, which is estimated to be a Gaussian with a 15±4 Å full width at half maximum in the plane of the interface. A simple model was used to study the effect of a weak localization potential on the overall width of the angular distribution of the photoemitted electrons, which exhibited little sensitivity to the details of the potential. This substantiates the validity of the localization size estimate.

  20. Confirmation of linear system theory prediction: Rate of change of Herrnstein's kappa as a function of response-force requirement.

    PubMed

    McDowell, J J; Wood, H M

    1985-01-01

    Four human subjects worked on all combinations of five variable-interval schedules and five reinforcer magnitudes ( cent/reinforcer) in each of two phases of the experiment. In one phase the force requirement on the operandum was low (1 or 11 N) and in the other it was high (25 or 146 N). Estimates of Herrnstein's kappa were obtained at each reinforcer magnitude. The results were: (1) response rate was more sensitive to changes in reinforcement rate at the high than at the low force requirement, (2) kappa increased from the beginning to the end of the magnitude range for all subjects at both force requirements, (3) the reciprocal of kappa was a linear function of the reciprocal of reinforcer magnitude for seven of the eight data sets, and (4) the rate of change of kappa was greater at the high than at the low force requirement by an order of magnitude or more. The second and third findings confirm predictions made by linear system theory, and replicate the results of an earlier experiment (McDowell & Wood, 1984). The fourth finding confirms a further prediction of the theory and supports the theory's interpretation of conflicting data on the constancy of Herrnstein's kappa.

  1. Detecting non-maxwellian electron velocity distributions at JET by high resolution Thomson scattering.

    PubMed

    Beausang, K V; Prunty, S L; Scannell, R; Beurskens, M N; Walsh, M J; de la Luna, E

    2011-03-01

    The present work is motivated by a long standing discrepancy between the electron temperature measurements of Thomson scattering (TS) and electron cyclotron emission (ECE) diagnostics for plasmas with strong auxiliary heating observed at both JET and TFTR above 6–7 keV, where in some cases the ECE electron temperature measurements can be 15%–20% higher than the TS measurements. Recent analysis based on ECE results at JET has shown evidence of distortions to the Maxwellian electron velocity distribution and a correlation with the TS and ECE discrepancies has been suggested. In this paper, a technique to determine the presence of non-Maxwellian behavior using TS diagnostics is outlined. The difficulties and limitations of modern TS system designs to determine the electron velocity distribution are also discussed. It is demonstrated that small deviations such as those suggested by previous ECE analysis could be potentially detected, depending on the spectral layout of the TS polychromators. The spectral layout of the JET high resolution Thomson scattering system is such that it could be used to determine these deviations between 1 and 6 keV, and the results presented here indicate that no evidence of non-Maxwellian behavior is observed in this range. In this paper, a modification to the current polychromator design is proposed, allowing non-Maxwellian distortions to be detected up to at least 10 keV.

  2. Hantaan virus nucleocapsid protein binds to importin alpha proteins and inhibits tumor necrosis factor alpha-induced activation of nuclear factor kappa B.

    PubMed

    Taylor, Shannon L; Frias-Staheli, Natalia; García-Sastre, Adolfo; Schmaljohn, Connie S

    2009-02-01

    Hantaviruses such as Hantaan virus (HTNV) and Andes virus cause two human diseases, hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome, respectively. For both, disease pathogenesis is thought to be immunologically mediated and there have been numerous reports of patients with elevated levels of proinflammatory and inflammatory cytokines, including tumor necrosis factor alpha (TNF-alpha), in their sera. Multiple viruses have developed evasion strategies to circumvent the host cell inflammatory process, with one of the most prevalent being the disruption of nuclear factor kappa B (NF-kappaB) activation. We hypothesized that hantaviruses might also moderate host inflammation by interfering with this pathway. We report here that the nucleocapsid (N) protein of HTNV was able to inhibit TNF-alpha-induced activation of NF-kappaB, as measured by a reporter assay, and the activation of endogenous p65, an NF-kappaB subunit. Surprisingly, there was no defect in the degradation of the inhibitor of NF-kappaB (IkappaB) protein, nor was there any alteration in the level of p65 expression in HTNV N-expressing cells. However, immunofluorescence antibody staining demonstrated that cells expressing HTNV N protein and a green fluorescent protein-p65 fusion had limited p65 nuclear translocation. Furthermore, we were able to detect an interaction between HTNV N protein and importin alpha, a nuclear import molecule responsible for shuttling NF-kappaB to the nucleus. Collectively, our data suggest that HTNV N protein can sequester NF-kappaB in the cytoplasm, thus inhibiting NF-kappaB activity. These findings, which were obtained using cells transfected with cDNA representing the HTNV N gene, were confirmed using HTNV-infected cells.

  3. Wall-loss distribution of charge breeding ions in an electron cyclotron resonance ion source

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jeong, S. C.; Oyaizu, M.; Imai, N.

    2011-03-15

    The ion loss distribution in an electron cyclotron resonance ion source (ECRIS) was investigated to understand the element dependence of the charge breeding efficiency in an electron cyclotron resonance (ECR) charge breeder. The radioactive {sup 111}In{sup 1+} and {sup 140}Xe{sup 1+} ions (typical nonvolatile and volatile elements, respectively) were injected into the ECR charge breeder at the Tokai Radioactive Ion Accelerator Complex to breed their charge states. Their respective residual activities on the sidewall of the cylindrical plasma chamber of the source were measured after charge breeding as functions of the azimuthal angle and longitudinal position and two-dimensional distributions ofmore » ions lost during charge breeding in the ECRIS were obtained. These distributions had different azimuthal symmetries. The origins of these different azimuthal symmetries are qualitatively discussed by analyzing the differences and similarities in the observed wall-loss patterns. The implications for improving the charge breeding efficiencies of nonvolatile elements in ECR charge breeders are described. The similarities represent universal ion loss characteristics in an ECR charge breeder, which are different from the loss patterns of electrons on the ECRIS wall.« less

  4. Proteomic screening of variola virus reveals a unique NF-kappaB inhibitor that is highly conserved among pathogenic orthopoxviruses.

    PubMed

    Mohamed, Mohamed R; Rahman, Masmudur M; Lanchbury, Jerry S; Shattuck, Donna; Neff, Chris; Dufford, Max; van Buuren, Nick; Fagan, Katharine; Barry, Michele; Smith, Scott; Damon, Inger; McFadden, Grant

    2009-06-02

    Identification of the binary interactions between viral and host proteins has become a valuable tool for investigating viral tropism and pathogenesis. Here, we present the first systematic protein interaction screening of the unique variola virus proteome by using yeast 2-hybrid screening against a variety of human cDNA libraries. Several protein-protein interactions were identified, including an interaction between variola G1R, an ankryin/F-box containing protein, and human nuclear factor kappa-B1 (NF-kappaB1)/p105. This represents the first direct interaction between a pathogen-encoded protein and NF-kappaB1/p105. Orthologs of G1R are present in a variety of pathogenic orthopoxviruses, but not in vaccinia virus, and expression of any one of these viral proteins blocks NF-kappaB signaling in human cells. Thus, proteomic screening of variola virus has the potential to uncover modulators of the human innate antiviral responses.

  5. SUPRATHERMAL ELECTRONS IN THE SOLAR CORONA: CAN NONLOCAL TRANSPORT EXPLAIN HELIOSPHERIC CHARGE STATES?

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Cranmer, Steven R., E-mail: scranmer@cfa.harvard.edu

    There have been several ideas proposed to explain how the Sun's corona is heated and how the solar wind is accelerated. Some models assume that open magnetic field lines are heated by Alfvén waves driven by photospheric motions and dissipated after undergoing a turbulent cascade. Other models posit that much of the solar wind's mass and energy is injected via magnetic reconnection from closed coronal loops. The latter idea is motivated by observations of reconnecting jets and also by similarities of ion composition between closed loops and the slow wind. Wave/turbulence models have also succeeded in reproducing observed trends inmore » ion composition signatures versus wind speed. However, the absolute values of the charge-state ratios predicted by those models tended to be too low in comparison with observations. This Letter refines these predictions by taking better account of weak Coulomb collisions for coronal electrons, whose thermodynamic properties determine the ion charge states in the low corona. A perturbative description of nonlocal electron transport is applied to an existing set of wave/turbulence models. The resulting electron velocity distributions in the low corona exhibit mild suprathermal tails characterized by ''kappa'' exponents between 10 and 25. These suprathermal electrons are found to be sufficiently energetic to enhance the charge states of oxygen ions, while maintaining the same relative trend with wind speed that was found when the distribution was assumed to be Maxwellian. The updated wave/turbulence models are in excellent agreement with solar wind ion composition measurements.« less

  6. Suprathermal Electrons in the Solar Corona: Can Nonlocal Transport Explain Heliospheric Charge States?

    NASA Astrophysics Data System (ADS)

    Cranmer, Steven R.

    2014-08-01

    There have been several ideas proposed to explain how the Sun's corona is heated and how the solar wind is accelerated. Some models assume that open magnetic field lines are heated by Alfvén waves driven by photospheric motions and dissipated after undergoing a turbulent cascade. Other models posit that much of the solar wind's mass and energy is injected via magnetic reconnection from closed coronal loops. The latter idea is motivated by observations of reconnecting jets and also by similarities of ion composition between closed loops and the slow wind. Wave/turbulence models have also succeeded in reproducing observed trends in ion composition signatures versus wind speed. However, the absolute values of the charge-state ratios predicted by those models tended to be too low in comparison with observations. This Letter refines these predictions by taking better account of weak Coulomb collisions for coronal electrons, whose thermodynamic properties determine the ion charge states in the low corona. A perturbative description of nonlocal electron transport is applied to an existing set of wave/turbulence models. The resulting electron velocity distributions in the low corona exhibit mild suprathermal tails characterized by "kappa" exponents between 10 and 25. These suprathermal electrons are found to be sufficiently energetic to enhance the charge states of oxygen ions, while maintaining the same relative trend with wind speed that was found when the distribution was assumed to be Maxwellian. The updated wave/turbulence models are in excellent agreement with solar wind ion composition measurements.

  7. kappa-Opioid receptor in humans: cDNA and genomic cloning, chromosomal assignment, functional expression, pharmacology, and expression pattern in the central nervous system.

    PubMed Central

    Simonin, F; Gavériaux-Ruff, C; Befort, K; Matthes, H; Lannes, B; Micheletti, G; Mattéi, M G; Charron, G; Bloch, B; Kieffer, B

    1995-01-01

    Using the mouse delta-opioid receptor cDNA as a probe, we have isolated genomic clones encoding the human mu- and kappa-opioid receptor genes. Their organization appears similar to that of the human delta receptor gene, with exon-intron boundaries located after putative transmembrane domains 1 and 4. The kappa gene was mapped at position q11-12 in human chromosome 8. A full-length cDNA encoding the human kappa-opioid receptor has been isolated. The cloned receptor expressed in COS cells presents a typical kappa 1 pharmacological profile and is negatively coupled to adenylate cyclase. The expression of kappa-opioid receptor mRNA in human brain, as estimated by reverse transcription-polymerase chain reaction, is consistent with the involvement of kappa-opioid receptors in pain perception, neuroendocrine physiology, affective behavior, and cognition. In situ hybridization studies performed on human fetal spinal cord demonstrate the presence of the transcript specifically in lamina II of the dorsal horn. Some divergences in structural, pharmacological, and anatomical properties are noted between the cloned human and rodent receptors. Images Fig. 3 Fig. 4 PMID:7624359

  8. LPS-induced NF-{kappa}B expression in THP-1Blue cells correlates with neopterin production and activity of indoleamine 2,3-dioxygenase

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Schroecksnadel, Sebastian; Jenny, Marcel; Division of Medical Biochemistry, Biocenter, Innsbruck Medical University, Innsbruck

    2010-09-03

    Research highlights: {yields} LPS induces NF-{kappa}B, neopterin formation and tryptophan degradation in THP-1 cells. {yields} Close dose- and time-dependent correlations exist between these biochemical events. {yields} Data provides some evidence for a parallel induction of them upon TLR stimulation. {yields} Results can be of considerable relevance also in vivo. -- Abstract: Neopterin production is induced in human monocyte-derived macrophages and dendritic cells upon stimulation with Th1-type cytokine interferon-{gamma} (IFN-{gamma}). In parallel, IFN-{gamma} induces the tryptophan-(trp)-degrading enzyme indoleamine 2,3-dioxygenase (IDO) and triggers the formation of reactive oxygen species (ROS). Translocation of the signal transduction element nuclear factor-{kappa}B (NF-{kappa}B) is induced bymore » ROS and accelerates the pro-inflammatory response by activation of other pro-inflammatory pathways. Therefore, a close relationship between NF-{kappa}B expression, the production of neopterin and the degradation of trp can be assumed, although this has not been demonstrated so far. In the present in vitro study we compared the influence of lipopolysaccharide (LPS) on NF-{kappa}B activation, neopterin formation and the degradation of trp in THP-1Blue cells, which represent the human myelomonocytic cell line THP-1 stably transfected with an NF-{kappa}B inducible reporter system. In cells stimulated with LPS, a significant induction of NF-{kappa}B was observed, and this was paralleled by an increase of kynureunine (kyn) and neopterin concentrations and a decline of trp. The increase of the kyn to trp quotient indicates accelerated IDO activity. Higher LPS concentrations and longer incubation of cells were associated with higher activities of all three biochemical pathways and significant correlations existed between NF-{kappa}B activation, neopterin release and trp degradation (all p < 0.001). We conclude that there is a parallel induction of NF-{kappa}B, neopterin

  9. Distinct roles of NF-{kappa}B p50 in the regulation of acetaminophen-induced inflammatory mediator production and hepatotoxicity

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dambach, Donna M.; Pharmaceutical Research Institute, Bristol-Myers Squibb, Princeton, NJ 08543; Durham, Stephen K.

    2006-03-01

    Oxidative stress plays an important role in acetaminophen (APAP)-induced hepatotoxicity. In addition to inducing direct cellular damage, oxidants can activate transcription factors including NF-{kappa}B, which regulate the production of inflammatory mediators implicated in hepatotoxicity. Here, we investigated the role of APAP-induced oxidative stress and NF-{kappa}B in inflammatory mediator production. Treatment of mice with APAP (300 mg/kg, i.p.) resulted in centrilobular hepatic necrosis and increased serum aminotransferase levels. This was correlated with depletion of hepatic glutathione and CuZn superoxide dismutase (SOD). APAP administration also increased expression of the proinflammatory mediators, interleukin-1{beta} (IL-1{beta}), tumor necrosis factor-{alpha} (TNF{alpha}), macrophage chemotactic protein-1 (MCP-1), andmore » KC/gro, and the anti-inflammatory cytokine, interleukin-10 (IL-10). Pretreatment of mice with the antioxidant, N-acetylcysteine (NAC) prevented APAP-induced depletion of glutathione and CuZnSOD, as well as hepatotoxicity. NAC also abrogated APAP-induced increases in TNF{alpha}, KC/gro, and IL-10, but augmented expression of the anti-inflammatory cytokines interleukin-4 (IL-4) and transforming growth factor-{beta} (TGF{beta}). No effects were observed on IL-1{beta} or MCP-1 expression. To determine if NF-{kappa}B plays a role in regulating mediator production, we used transgenic mice with a targeted disruption of the gene for NF-{kappa}B p50. As observed with NAC pretreatment, the loss of NF-{kappa}B p50 was associated with decreased ability of APAP to upregulate TNF{alpha}, KC/gro, and IL-10 expression and increased expression of IL-4 and TGF{beta}. However, in contrast to NAC pretreatment, the loss of p50 had no effect on APAP-induced hepatotoxicity. These data demonstrate that APAP-induced cytokine expression in the liver is influenced by oxidative stress and that this is dependent, in part, on NF-{kappa}B. However, NF-{kappa}B p50

  10. Wall-loss distribution of charge breeding ions in an electron cyclotron resonance ion source

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jeong, S. C.; Oyaizu, M.; Imai, N.

    2012-02-15

    We investigated the ion-loss distribution on the sidewall of an electron cyclotron resonance (ECR) plasma chamber using the 18-GHz ECR charge breeder at the Tokai Radioactive Ion Accelerator Complex (TRIAC). Similarities and differences between the ion-loss distributions (longitudinal and azimuthal) of different ion species (i.e., radioactive {sup 111}In{sup 1+} and {sup 140}Xe{sup 1+} ions that are typical volatile and nonvolatile elements) was qualitatively discussed to understand the element dependence of the charge breeding efficiency. Especially, the similarities represent universal ion loss characteristics in an ECR charge breeder, which are different from the loss patterns of electrons on the ECRIS wall.

  11. Electron energy distribution function in a low-power Hall thruster discharge and near-field plume

    NASA Astrophysics Data System (ADS)

    Tichý, M.; Pétin, A.; Kudrna, P.; Horký, M.; Mazouffre, S.

    2018-06-01

    Electron temperature and plasma density, as well as the electron energy distribution function (EEDF), have been obtained inside and outside the dielectric channel of a 200 W permanent magnet Hall thruster. Measurements were carried out by means of a cylindrical Langmuir probe mounted onto a compact fast moving translation stage. The 3D particle-in cell numerical simulations complement experiments. The model accounts for the crossed electric and magnetic field configuration in a weakly collisional regime where only electrons are magnetized. Since only the electron dynamics is of interest in this study, an artificial mass of ions corresponding to mi = 30 000me was used to ensure ions could be assumed at rest. The simulation domain is located at the thruster exit plane and does not include the cathode. The measured EEDF evidences a high-energy electron population that is superimposed onto the low energy bulk population outside the channel. Inside the channel, the EEDF is close to Maxwellian. Both the experimental and numerical EEDF depart from an equilibrium distribution at the channel exit plane, a region of high magnetic field. We therefore conclude that the fast electron group found in the experiment corresponds to the electrons emitted by the external cathode that reach the thruster discharge without experiencing collision events.

  12. Non-equilibrium electron energy distributions in HII regions: Implications for abundance determinations

    NASA Astrophysics Data System (ADS)

    Dopita, Michael; Nicholls, David

    2012-07-01

    Although the analysis of HII region emission lines provides the main way of probing the chemical evolution of the universe throughout cosmic time, currently significant (factor of 2) discrepancies exist between the different methods (principally the strong line, electron temperature and recombination line methods) used to calibrate the cosmic chemical abundance scale. Although effects such as temperature fluctuations and geometrical effects have been invoked, these fail to explain the observations, particularly in the UV. Here we will show that there exists good grounds for supposing that the electrons in HII regions, as in other space plasmas, are not distributed according to a Boltzmann law. Rather, they follow a κ- distribution with κ ˜ 10. With this novel formulation, we can resolve the abundance discrepancies which have plagued this field for over three decades. Interestingly enough, the size of the correction in emission line strengths increases as we go into the UV.

  13. Effect of anomalous electron cross-field transport on electron energy distribution function in a DC-RF magnetized plasma discharge

    NASA Astrophysics Data System (ADS)

    Raitses, Yevgeny; Donnelly, Vincent M.; Kaganovich, Igor D.; Godyak, Valery

    2013-10-01

    The application of the magnetic field in a low pressure plasma can cause a spatial separation of cold and hot electron groups. This so-called magnetic filter effect is not well understood and is the subject of our studies. In this work, we investigate electron energy distribution function in a DC-RF plasma discharge with crossed electric and magnetic field operating at sub-mtorr pressure range of xenon gas. Experimental studies showed that the increase of the magnetic field leads to a more uniform profile of the electron temperature across the magnetic field. This surprising result indicates the importance of anomalous electron transport that causes mixing of hot and cold electrons. High-speed imaging and probe measurements revealed a coherent structure rotating in E cross B direction with frequency of a few kHz. Similar to spoke oscillations reported for Hall thrusters, this rotating structure conducts the largest fraction of the cross-field current. This work was supported by DOE contract DE-AC02-09CH11466.

  14. X-rays diagnostics of the hot electron energy distribution in the intense laser interaction with metal targets

    NASA Astrophysics Data System (ADS)

    Kostenko, O. F.; Andreev, N. E.; Rosmej, O. N.

    2018-03-01

    A two-temperature hot electron energy distribution has been revealed by modeling of bremsstrahlung emission, measured by the radiation attenuation and half-shade methods, and Kα emission from a massive silver cylinder irradiated by a subpicosecond s-polarized laser pulse with a peak intensity of about 2 × 1019 W/cm2. To deduce parameters of the hot electron spectrum, we have developed semi-analytical models of generation and measurements of the x-rays. The models are based on analytical expressions and tabulated data on electron stopping power as well as cross-sections of generation and absorption of the x-rays. The Kα emission from thin silver foils deposited on low-Z substrates, both conducting and nonconducting, has been used to verify the developed models and obtained hot electron spectrum. The obtained temperatures of the colder and hotter electron components are in agreement with the values predicted by kinetic simulations of the cone-guided approach to fast ignition [Chrisman et al., Phys. Plasmas 15, 056309 (2008)]. The temperature of the low-energy component of the accelerated electron spectrum is well below the ponderomotive scaling and Beg's law. We have obtained relatively low conversion efficiency of laser energy into the energy of hot electrons propagating through the solid target of about 2%. It is demonstrated that the assumption about a single-temperature hot electron energy distribution with the slope temperature described by the ponderomotive scaling relationship, without detailed analysis of the hot electron spectrum, can lead to strong overestimation of the laser-to-electron energy-conversion efficiency, in particular, the conversion efficiency of laser energy into the high-temperature component of the hot electron distribution.

  15. Nonlinear saturation of wave packets excited by low-energy electron horseshoe distributions.

    PubMed

    Krafft, C; Volokitin, A

    2013-05-01

    Horseshoe distributions are shell-like particle distributions that can arise in space and laboratory plasmas when particle beams propagate into increasing magnetic fields. The present paper studies the stability and the dynamics of wave packets interacting resonantly with electrons presenting low-energy horseshoe or shell-type velocity distributions in a magnetized plasma. The linear instability growth rates are determined as a function of the ratio of the plasma to the cyclotron frequencies, of the velocity and the opening angle of the horseshoe, and of the relative thickness of the shell. The nonlinear stage of the instability is investigated numerically using a symplectic code based on a three-dimensional Hamiltonian model. Simulation results show that the dynamics of the system is mainly governed by wave-particle interactions at Landau and normal cyclotron resonances and that the high-order normal cyclotron resonances play an essential role. Specific features of the dynamics of particles interacting simultaneously with two or more waves at resonances of different natures and orders are discussed, showing that such complex processes determine the main characteristics of the wave spectrum's evolution. Simulations with wave packets presenting quasicontinuous spectra provide a full picture of the relaxation of the horseshoe distribution, revealing two main phases of the evolution: an initial stage of wave energy growth, characterized by a fast filling of the shell, and a second phase of slow damping of the wave energy, accompanied by final adjustments of the electron distribution. The influence of the density inhomogeneity along the horseshoe on the wave-particle dynamics is also discussed.

  16. Pasteurella haemolytica leukotoxin and endotoxin induced cytokine gene expression in bovine alveolar macrophages requires NF-kappaB activation and calcium elevation.

    PubMed

    Hsuan, S L; Kannan, M S; Jeyaseelan, S; Prakash, Y S; Malazdrewich, C; Abrahamsen, M S; Sieck, G C; Maheswaran, S K

    1999-05-01

    In bovine alveolar macrophages (BAMs), exposure to leukotoxin (Lkt) and endotoxin (LPS) from Pasteurella haemolytica results in expression of inflammatory cytokine genes and intracellular calcium ([Ca2+]i) elevation. Leukotoxin from P. haemolytica interacts only with leukocytes and platelets from ruminant species. Upregulation of cytokine genes in different cells by LPS involves activation of the transcription factor NF-kappaB (NF-kappaB), resulting in its translocation from the cytoplasm to the nucleus. Using immunocytochemical staining and confocal imaging, we studied whether NF-kappaB activation represents a common mechanism for the expression of multiple cytokine genes in BAMs (Lkt-susceptible cells) stimulated with Lkt and LPS. Bovine pulmonary artery endothelial cells and porcine alveolar macrophages were used as nonsusceptible cells. The role of Ca2+ and tyrosine kinases in NF-kappaB activation and inflammatory cytokine gene expression was studied, since an inhibitor of tyrosine kinases attenuates LPS-induced [Ca2+]i elevation in BAMs. The results are summarized as follows: (a) Lkt induced NF-kappaB activation and [Ca2+]i elevation only in BAMs, while LPS effects were demonstrable in all cell types; (b) chelation of [Ca2+]i blocked NF-kappaB activation and IL-1beta, TNFalpha, and IL-8 mRNA expression; and (c) tyrosine kinase inhibitor herbimycin A blocked expression of all three cytokine genes in BAMs stimulated with Lkt, while only the expression of IL-1beta was blocked in BAMs stimulated with LPS. We conclude that cytokine gene expression in BAMs requires NF-kappaB activation and [Ca2+]i elevation, and Lkt effects exhibit cell type- and species specificity. Copyright 1999 Academic Press.

  17. BCL11B enhances TCR/CD28-triggered NF-kappaB activation through up-regulation of Cot kinase gene expression in T-lymphocytes.

    PubMed

    Cismasiu, Valeriu B; Duque, Javier; Paskaleva, Elena; Califano, Danielle; Ghanta, Sailaja; Young, Howard A; Avram, Dorina

    2009-01-15

    BCL11B is a transcriptional regulator with an important role in T-cell development and leukaemogenesis. We demonstrated recently that BCL11B controls expression from the IL (interleukin)-2 promoter through direct binding to the US1 (upstream site 1). In the present study, we provide evidence that BCL11B also participates in the activation of IL-2 gene expression by enhancing NF-kappaB (nuclear factor kappaB) activity in the context of TCR (T-cell receptor)/CD28-triggered T-cell activation. Enhanced NF-kappaB activation is not a consequence of BCL11B binding to the NF-kappaB response elements or association with the NF-kappaB-DNA complexes, but rather the result of higher translocation of NF-kappaB to the nucleus caused by enhanced degradation of IkappaB (inhibitor of NF-kappaB). The enhanced IkappaB degradation in cells with increased levels of BCL11B was specific for T-cells activated through the TCR, but not for cells activated through TNFalpha (tumour necrosis factor alpha) or UV light, and was caused by increased activity of IkappaB kinase, as indicated by its increase in phosphorylation. As BCL11B is a transcription factor, we investigated whether the expression of genes upstream of IkappaB kinase in the TCR/CD28 signalling pathway was affected by increased BCL11B expression, and found that Cot (cancer Osaka thyroid oncogene) kinase mRNA levels were elevated. Cot kinase is known to promote enhanced IkappaB kinase activity, which results in the phosphorylation and degradation of IkappaB and activation of NF-kappaB. The implied involvement of Cot kinase in BCL11B-mediated NF-kappaB activation in response to TCR activation is supported by the fact that a Cot kinase dominant-negative mutant or Cot kinase siRNA (small interfering RNA) knockdown blocked BCL11B-mediated NF-kappaB activation. In support of our observations, in the present study we report that BCL11B enhances the expression of several other NF-kappaB target genes, in addition to IL-2. In addition, we

  18. Dissociative Ionization and Product Distributions of Benzene and Pyridine by Electron Impact

    NASA Technical Reports Server (NTRS)

    Dateo, Christopher E.; Huo, Winifred M.; Fletcher, Graham D.

    2003-01-01

    We report a theoretical study of the dissociative ionization (DI) and product distributions of benzene (C6H6) and pyridine (C5H5N) from their low-lying ionization channels. Our approach makes use of the fact that electronic motion is much faster than nuclear motion allowing DI to be treated as a two-step process. The first step is the electron-impact ionization resulting in an ion with the same nuclear geometry as the neutral molecule. In the second step, the nuclei relax from the initial geometry and undergo unimolecular dissociation. For the ionization process we use the improved binary-encounter dipole (iBED) model [W.M. Huo, Phys. Rev. A64,042719-I (2001)]. For the unimolecular dissociation, we use multiconfigurational self-consistent field (MCSCF) methods to determine the steepest descent pathways to the possible product channels. More accurate methods are then used to obtain better energetics of the paths which are used to determine unimolecular dissociation probabilities and product distributions. Our analysis of the dissociation products and the thresholds of their productions for benzene are compared with the recent dissociative photoionization meausurements of benzene by Feng et al. [R. Feng, G. Cooper, C.E. Brion, J. Electron Spectrosc. Relat. Phenom. 123,211 (2002)] and the dissociative photoionization measurements of pyridine by Tixier et al. [S. Tixier, G. Cooper, R. Feng, C.E. Brion, J. Electron Spectrosc. Relat. Phenom. 123,185 (2002)] using dipole (e,e+ion) coincidence spectroscopy.

  19. Structure of new carotenoids with the 6-oxo-kappa end group from the fruits of paprika, Capsicum annuum.

    PubMed

    Maoka, Takashi; Akimoto, Naoshige; Fujiwara, Yasuhiro; Hashimoto, Keiji

    2004-01-01

    New carotenoids 1 and 2 were isolated as minor components from the ripe fruits of paprika (Capsicum annuum). The structures of 1 and 2 were determined to be (3R,5'R)-3-hydroxy-beta,kappa-caroten-6'-one and (5'R)-3,4-didehydro-beta,kappa-caroten-6'-one, respectively, from UV-vis, NMR, CD, HRFABMS, and FABMS/MS spectra.

  20. Down-regulation of PKHD1 induces cell apoptosis through PI3K and NF-{kappa}B pathways

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sun, Liping; Wang, Shixuan; Hu, Chaofeng

    2011-04-15

    Mutations in PKHD1 (polycystic kidney and hepatic disease gene 1) gene cause the autosomal recessive polycystic kidney disease (ARPKD). Fibrocystin/polyductin (FPC), encoded by PKHD1, is a membrane-associated receptor-like protein. Although it is widely accepted that cystogenesis is mostly due to aberrant cell proliferation and apoptosis, it is still unclear how apoptosis is regulated. The aim of this study is to analyze the relationship among apoptosis, phosphatidylinositol 3-kinase (PI3K)/Akt and nuclear factor {kappa}B (NF-{kappa}B) in FPC knockdown kidney cells. We show that PKHD1-silenced HEK293 cells demonstrate a higher PI3K/Akt activity. Selective inhibition of PI3K/Akt using LY294002 or wortmannin in these cellsmore » increases serum starvation-induced HEK293 cell apoptosis with a concomitant decrease in cell proliferation and higher caspase-3 activity. PI3K/Akt inhibition also leads to increased NF-{kappa}B activity in these cells. We conclude that the PI3K/Akt pathway is involved in apoptotic function in PKHD1-silenced cells, and PI3K/Akt inhibition correlates with upregulation of NF-{kappa}B activity. These observations provide a potential platform for determining FPC function and therapeutic investigation of ARPKD.« less

  1. Selective kappa-opioid agonists: synthesis and structure-activity relationships of piperidines incorporating on oxo-containing acyl group.

    PubMed

    Giardina, G; Clarke, G D; Dondio, G; Petrone, G; Sbacchi, M; Vecchietti, V

    1994-10-14

    This study describes the synthesis and the structure-activity relationships (SARs) of the (S)-(-)-enantiomers of a novel class of 2-(aminomethyl)piperidine derivatives, using kappa-opioid binding affinity and antinociceptive potency as the indices of biological activity. Compounds incorporating the 1-tetralon-6-ylacetyl residue (30 and 34-45) demonstrated an in vivo antinociceptive activity greater than predicted on the basis of their kappa-binding affinities. In particular, (2S)-2-[(dimethylamino)methyl]-1-[(5,6,7,8-tetrahydro-5-oxo-2- naphthyl)acetyl]piperidine (34) was found to have a potency similar to spiradoline in animal models of antinociception after subcutaneous administration, with ED50s of 0.47 and 0.73 mumol/kg in the mouse and in the rat abdominal constriction tests, respectively. Further in vivo studies in mice and/or rats revealed that compound 34, compared to other selective kappa-agonists, has a reduced propensity to cause a number of kappa-related side effects, including locomotor impairment/sedation and diuresis, at antinociceptive doses. For example, it has an ED50 of 26.5 mumol/kg sc in the rat rotarod model, exhibiting a ratio of locomotor impairment/sedation vs analgesia of 36. Possible reasons for this differential activity and its clinical consequence are discussed.

  2. Propagation of cylindrical ion acoustic waves in a plasma with q-nonextensive electrons with nonthermal distribution

    NASA Astrophysics Data System (ADS)

    El-Depsy, A.; Selim, M. M.

    2016-12-01

    The propagation of ion acoustic waves (IAWs) in a cylindrical collisionless unmagnetized plasma, containing ions and electrons is investigated. The electrons are considered to be nonextensive and follow nonthermal distribution. The reductive perturbation technique (RPT) is used to obtain a nonlinear cylindrical Kadomtsev-Petviashvili (CKP) evolution equation. This equation is solved analytically. The effects of plasma parameters on the IAWs characteristics are discussed in details. Both compressive and rarefactive solitons are found to be created in the proposed plasma system. The profile of IAWs is found to depend on the nonextensive and nonthermal parameters. The present study is useful for understanding IAWs in the regions where mixed electron distribution in space, or laboratory plasmas, exist.

  3. Comparisons of ionospheric electron density distributions reconstructed by GPS computerized tomography, backscatter ionograms, and vertical ionograms

    NASA Astrophysics Data System (ADS)

    Zhou, Chen; Lei, Yong; Li, Bofeng; An, Jiachun; Zhu, Peng; Jiang, Chunhua; Zhao, Zhengyu; Zhang, Yuannong; Ni, Binbin; Wang, Zemin; Zhou, Xuhua

    2015-12-01

    Global Positioning System (GPS) computerized ionosphere tomography (CIT) and ionospheric sky wave ground backscatter radar are both capable of measuring the large-scale, two-dimensional (2-D) distributions of ionospheric electron density (IED). Here we report the spatial and temporal electron density results obtained by GPS CIT and backscatter ionogram (BSI) inversion for three individual experiments. Both the GPS CIT and BSI inversion techniques demonstrate the capability and the consistency of reconstructing large-scale IED distributions. To validate the results, electron density profiles obtained from GPS CIT and BSI inversion are quantitatively compared to the vertical ionosonde data, which clearly manifests that both methods output accurate information of ionopsheric electron density and thereby provide reliable approaches to ionospheric soundings. Our study can improve current understanding of the capability and insufficiency of these two methods on the large-scale IED reconstruction.

  4. Density-functional theory based on the electron distribution on the energy coordinate

    NASA Astrophysics Data System (ADS)

    Takahashi, Hideaki

    2018-03-01

    We developed an electronic density functional theory utilizing a novel electron distribution n(ɛ) as a basic variable to compute ground state energy of a system. n(ɛ) is obtained by projecting the electron density n({\\boldsymbol{r}}) defined on the space coordinate {\\boldsymbol{r}} onto the energy coordinate ɛ specified with the external potential {\\upsilon }ext}({\\boldsymbol{r}}) of interest. It was demonstrated that the Kohn-Sham equation can also be formulated with the exchange-correlation functional E xc[n(ɛ)] that employs the density n(ɛ) as an argument. It turned out an exchange functional proposed in our preliminary development suffices to describe properly the potential energies of several types of chemical bonds with comparable accuracies to the corresponding functional based on local density approximation. As a remarkable feature of the distribution n(ɛ) it inherently involves the spatially non-local information of the exchange hole at the bond dissociation limit in contrast to conventional approximate functionals. By taking advantage of this property we also developed a prototype of the static correlation functional E sc including no empirical parameters, which showed marked improvements in describing the dissociations of covalent bonds in {{{H}}}2,{{{C}}}2{{{H}}}4 and {CH}}4 molecules.

  5. Simulation studies of plasma waves in the electron foreshock - The generation of Langmuir waves by a gentle bump-on-tail electron distribution

    NASA Technical Reports Server (NTRS)

    Dum, C. T.

    1990-01-01

    Particle simulation experiments were used to study the basic physical ingredients needed for building a global model of foreshock wave phenomena. In particular, the generation of Langmuir waves by a gentle bump-on-tail electron distribution is analyzed. It is shown that, with appropriately designed simulations experiments, quasi-linear theory can be quantitatively verified for parameters corresponding to the electron foreshock.

  6. Nuclear NF-kappaB p65 phosphorylation at serine 276 by protein kinase A contributes to the malignant phenotype of head and neck cancer.

    PubMed

    Arun, Pattatheyil; Brown, Matthew S; Ehsanian, Reza; Chen, Zhong; Van Waes, Carter

    2009-10-01

    Aberrant nuclear activation and phosphorylation of the canonical NF-kappaB subunit RELA/p65 at Serine-536 by inhibitor kappaB kinase is prevalent in head and neck squamous cell carcinoma (HNSCC), but the role of other kinases in NF-kappaB activation has not been well defined. Here, we investigated the prevalence and function of p65-Ser276 phosphorylation by protein kinase A (PKA) in the malignant phenotype and gene transactivation, and studied p65-Ser276 as a potential target for therapy. Phospho and total p65 protein expression and localization were determined in HNSCC tissue array and in cell lines. The effects of the PKA inhibitor H-89 on NF-kappaB activation, downstream gene expression, cell proliferation and cell cycle were examined. Knockdown of PKA by specific siRNA confirmed the specificity. NF-kappaB p65 phosphorylated at Ser276 was prevalent in HNSCC and adjacent dysplastic mucosa, but localized to the cytoplasm in normal mucosa. In HNSCC lines, tumor necrosis factor-alpha (TNF-alpha) significantly increased, whereas H-89 inhibited constitutive and TNF-alpha-induced nuclear p65 (Ser276) phosphorylation, and significantly suppressed NF-kappaB and target gene IL-8 reporter activity. Knockdown of PKA by small interfering RNA inhibited NF-kappaB, IL-8, and BCL-XL reporter gene activities. H-89 suppressed cell proliferation, induced cell death, and blocked the cell cycle in G(1)-S phase. Consistent with its biological effects, H-89 down-modulated expression of NF-kappaB-related genes Cyclin D1, BCL2, BCL-XL, COX2, IL-8, and VEGF, as well as induced cell cycle inhibitor p21(CIP1/WAF1), while suppressing proliferative marker Ki67. NF-kappaB p65 (Ser276) phosphorylation by PKA promotes the malignant phenotype and holds potential as a therapeutic target in HNSCC.

  7. The Problems with the Kappa Statistic as a Metric of Interobserver Agreement on Lesion Detection Using a Third-reader Approach When Locations Are Not Prespecified.

    PubMed

    Shih, Joanna H; Greer, Matthew D; Turkbey, Baris

    2018-03-16

    To point out the problems with Cohen kappa statistic and to explore alternative metrics to determine interobserver agreement on lesion detection when locations are not prespecified. Use of kappa and two alternative methods, namely index of specific agreement (ISA) and modified kappa, for measuring interobserver agreement on the location of detected lesions are presented. These indices of agreement are illustrated by application to a retrospective multireader study in which nine readers detected and scored prostate cancer lesions in 163 consecutive patients (n = 110 cases, n = 53 controls) using the guideline of Prostate Imaging Reporting and Data System version 2 on multiparametric magnetic resonance imaging. The proposed modified kappa, which properly corrects for the amount of agreement by chance, is shown to be approximately equivalent to the ISA. In the prostate cancer data, average kappa, modified kappa, and ISA equaled 30%, 55%, and 57%, respectively, for all lesions and 20%, 87%, and 87%, respectively, for index lesions. The application of kappa could result in a substantial downward bias in reader agreement on lesion detection when locations are not prespecified. ISA is recommended for assessment of reader agreement on lesion detection. Published by Elsevier Inc.

  8. NASAwide electronic publishing system-prototype STI electronic document distribution: Stage-4 evaluation report. Part 2; Appendices

    NASA Technical Reports Server (NTRS)

    Tuey, Richard C.; Collins, Mary; Caswell, Pamela; Haynes, Bob; Nelson, Michael L.; Holm, Jeanne; Buquo, Lynn; Tingle, Annette; Cooper, Bill; Stiltner, Roy

    1996-01-01

    This evaluation report contains an introduction, seven chapters, and five appendices. The Introduction describes the purpose, conceptual framework, functional description, and technical report server of the Scientific and Technical Information (STI) Electronic Document Distribution (EDD) project. Chapter 1 documents the results of the prototype STI EDD in actual operation. Chapter 2 documents each NASA center's post processing publication processes. Chapter 3 documents each center's STI software, hardware. and communications configurations. Chapter 7 documents STI EDD policy, practices, and procedures. The appendices consist of (A) the STI EDD Project Plan, (B) Team members, (C) Phasing Schedules, (D) Accessing On-line Reports, and (E) Creating an HTML File and Setting Up an xTRS. In summary, Stage 4 of the NASAwide Electronic Publishing System is the final phase of its implementation through the prototyping and gradual integration of each NASA center's electronic printing systems, desk top publishing systems, and technical report servers, to be able to provide to NASA's engineers, researchers, scientists, and external users, the widest practicable and appropriate dissemination of information concerning its activities and the result thereof to their work stations.

  9. Measurement of the energy distribution of electrons escaping minimum-B ECR plasmas

    NASA Astrophysics Data System (ADS)

    Izotov, I.; Tarvainen, O.; Skalyga, V.; Mansfeld, D.; Kalvas, T.; Koivisto, H.; Kronholm, R.

    2018-02-01

    The measurement of the electron energy distribution (EED) of electrons escaping axially from a minimum-B electron cyclotron resonance ion source (ECRIS) is reported. The experimental data were recorded with a room-temperature 14 GHz ECRIS at the JYFL accelerator laboratory. The electrons escaping through the extraction mirror of the ion source were detected with a secondary electron amplifier placed downstream from a dipole magnet serving as an electron spectrometer with 500 eV resolution. It was discovered that the EED in the range of 5-250 keV is strongly non-Maxwellian and exhibits several local maxima below 20 keV energy. It was observed that the most influential ion source operating parameter on the EED is the magnetic field strength, which affected the EED predominantly at energies less than 100 keV. The effects of the microwave power and frequency, ranging from 100 to 600 W and 11 to 14 GHz, respectively, on the EED were found to be less significant. The presented technique and experiments enable the comparison between direct measurement of the EED and results derived from Bremsstrahlung diagnostics, the latter being severely complicated by the non-Maxwellian nature of the EED reported here. The role of RF pitch angle scattering on electron losses and the relation between the EED of the axially escaping electrons and the EED of the confined electrons are discussed.

  10. Nucleotide sequences of bovine alpha S1- and kappa-casein cDNAs.

    PubMed Central

    Stewart, A F; Willis, I M; Mackinlay, A G

    1984-01-01

    The nucleotide sequences corresponding to bovine alpha S1- and kappa-casein mRNAs are presented. An unusual alpha S1-casein cDNA has been characterised whose 5' end commences upstream from its putative TATA box. The alpha S1-casein mRNA is compared to rat alpha-casein mRNA and two components of divergence are identified. Firstly, the two sequences have diverged at a high point mutation rate and the rate of amino acid replacement by this mechanism is at least as great as the rate of divergence of any other part of the mRNAs. Secondly, the protein coding sequence has been subjected to several insertion/deletion events, one of which may be an example of exon shuffling . The kappa-casein mRNA sequence verifies the proposition that it has arisen from a different ancestral gene to the other caseins. Images PMID:6328443

  11. Protective protein/cathepsin A down-regulates osteoclastogenesis by associating with and degrading NF-kappaB p50/p65.

    PubMed

    Masuhara, Masaaki; Sato, Takuya; Hada, Naoto; Hakeda, Yoshiyuki

    2009-01-01

    Disruption of the cooperative function balance between osteoblasts and osteoclasts causes various bone disorders, some of which are attributed to abnormal osteoclast recruitment. Osteoclast differentiation is dependent on the receptor activator of nuclear factor (NF)-kappaB ligand (RANKL) as well as the macrophage colony-stimulating factor. The osteoclast formation induced by cytokines requires activation of NF-kappaB, AP-1 and nuclear factor of activated T cells c1. However, osteoclasts are not the only cell types that express these transcription factors, suggesting that some unknown molecules specific for osteoclasts may associate with the transcription factors. Here, we explored the possibility of molecules binding directly to NF-kappaB and cloned protective protein/cathepsin A (PPCA) by yeast two-hybrid screening using a cDNA library of osteoclast precursors. Forced expression of PPCA with p50/p65 in HEK293 cells decreased both the level of p50/p65 proteins and the transcriptional activity. Abundant PPCA was detected in the lysosomes of the transfected HEK293 cells, but a small amount of this enzyme was also present in the cytosolic fraction. In addition, over-expression of PPCA caused the disappearance of p50/p65 in both the lysosomal and cytosolic fractions. PPCA was expressed throughout osteoclastogenesis, and the expression was slightly up-regulated by RANKL signaling. Knockdown of PPCA in osteoclast precursors with PPCA siRNA stimulated binding of nuclear proteins to oligonucleotides containing an NF-kappaB binding motif and increased osteoclastogenesis. Our present results indicate a novel role for PPCA in osteoclastogenesis via down-regulation of NF-kappaB activity and suggest a new function for PPCA as an NF-kappaB-degrading enzyme in addition to its known multifunctional properties.

  12. Cluster/Peace Electrons Velocity Distribution Function: Modeling the Strahl in the Solar Wind

    NASA Technical Reports Server (NTRS)

    Figueroa-Vinas, Adolfo; Gurgiolo, Chris; Goldstein, Melvyn L.

    2008-01-01

    We present a study of kinetic properties of the strahl electron velocity distribution functions (VDF's) in the solar wind. These are used to investigate the pitch-angle scattering and stability of the population to interactions with electromagnetic (whistler) fluctuations. The study is based on high time resolution data from the Cluster/PEACE electron spectrometer. Our study focuses on the mechanisms that control and regulate the pitch-angle and stability of strahl electrons in the solar wind; mechanisms that are not yet well understood. Various parameters are investigated such as the electron heat-flux and temperature anisotropy. The goal is to check whether the strahl electrons are constrained by some instability (e.g., the whistler instability), or are maintained by other types of processes. The electron heat-flux and temperature anisotropy are determined by fitting the VDF's to a spectral spherical harmonic model from which the moments are derived directly from the model coefficients.

  13. Overexpression of cellular repressor of E1A-stimulated genes inhibits TNF-{alpha}-induced apoptosis via NF-{kappa}B in mesenchymal stem cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Peng, Cheng-Fei; Cardiovascular Research Institute and Department of Cardiology, Shenyang Northern Hospital, Shenyang; Han, Ya-Ling, E-mail: hanyaling53@gmail.com

    2011-03-25

    Research highlights: {yields} CREG protected MSCs from tumor necrosis factor-{alpha} (TNF-{alpha}) induced apoptosis. {yields} CREG inhibits the phosphorylation of I{kappa}B{alpha} and prevents the activation of NF-{kappa}B. {yields} CREG inhibits NF-{kappa}B nuclear translocation and pro-apoptosis protein transcription. {yields} CREG anti-apoptotic effect involves inhibition of the death receptor pathway. {yields} p53 is downregulated by CREG via NF-{kappa}B pathway under TNF-{alpha} stimulation. -- Abstract: Bone marrow-derived mesenchymal stem cells (MSCs) show great potential for therapeutic repair after myocardial infarction. However, poor viability of transplanted MSCs in the ischemic heart has limited their use. Cellular repressor of E1A-stimulated genes (CREG) has been identified asmore » a potent inhibitor of apoptosis. This study therefore aimed to determine if rat bone marrow MSCs transfected with CREG-were able to effectively resist apoptosis induced by inflammatory mediators, and to demonstrate the mechanism of CREG action. Apoptosis was determined by flow cytometric and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling assays. The pathways mediating these apoptotic effects were investigated by Western blotting. Overexpression of CREG markedly protected MSCs from tumor necrosis factor-{alpha} (TNF-{alpha}) induced apoptosis by 50% after 10 h, through inhibition of the death-receptor-mediated apoptotic pathway, leading to attenuation of caspase-8 and caspase-3. Moreover, CREG resisted the serine phosphorylation of I{kappa}B{alpha} and prevented the nuclear translocation of the transcription factor nuclear factor-{kappa}B (NF-{kappa}B) under TNF-{alpha} stimulation. Treatment of cells with the NF-{kappa}B inhibitor pyrrolidine dithiocarbamate (PDTC) significantly increased the transcription of pro-apoptosis proteins (p53 and Fas) by NF-{kappa}B, and attenuated the anti-apoptotic effects of CREG on MSCs. The results of this

  14. Thalidomide in rat liver cirrhosis: blockade of tumor necrosis factor-alpha via inhibition of degradation of an inhibitor of nuclear factor-kappaB.

    PubMed

    Paul, Shelley Chireyath; Lv, Peng; Xiao, Yan-Jv; An, Ping; Liu, Shi-Quan; Luo, He-Sheng

    2006-01-01

    Thalidomide inhibited tumor necrosis factor-alpha (TNF-alpha) effectively in many trials. The aim of this study was to investigate the effect of thalidomide on the expression of nuclear factor-kappaB (NF-kappaB), inhibitor of NF-kappaB (IkappaB) and TNF-alpha in a rat model of liver cirrhosis. Liver cirrhosis was achieved by intraperitoneal injection of carbon tetrachloride thrice weekly, and thalidomide (10 or 100 mg/kg/day) was given daily by intragastric route for 8 weeks. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), prealbumin (PA), hyaluronic acid (HA) and laminin (LN), and hydroxyproline (HYP), NF-kappaBp65, alpha-smooth muscle actin (alpha-SMA) protein and TNF-alpha mRNA were studied in the liver, IkappaBalpha and TNF-alpha protein in the cytoplasm and NF-kappaBp65 protein in the nucleus. Compared with nontreated cirrhotic rats, the histopathology of rats given thalidomide (100 mg/kg) was significantly better. Serum ALT, AST, HA and LN and HYP content in the liver were significantly decreased and PA was elevated (p < 0.01) in this group; the expression of TNF-alpha mRNA and protein, NF-kappaBp65 and alpha-SMA were significantly decreased and IkappaBalpha protein was also elevated (p < 0.01). Thalidomide downregulates NF-kappaB-induced TNF-alpha and activates hepatic stellate cells (HSC) via inhibition of IkappaB degradation to prevent liver cirrhosis. Copyright 2006 S. Karger AG, Basel.

  15. Study of dust particle charging in weakly ionized inert gases taking into account the nonlocality of the electron energy distribution function

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Filippov, A. V., E-mail: fav@triniti.ru; Dyatko, N. A.; Kostenko, A. S.

    2014-11-15

    The charging of dust particles in weakly ionized inert gases at atmospheric pressure has been investigated. The conditions under which the gas is ionized by an external source, a beam of fast electrons, are considered. The electron energy distribution function in argon, krypton, and xenon has been calculated for three rates of gas ionization by fast electrons: 10{sup 13}, 10{sup 14}, and 10{sup 15} cm{sup −1}. A model of dust particle charging with allowance for the nonlocal formation of the electron energy distribution function in the region of strong plasma quasi-neutrality violation around the dust particle is described. The nonlocalitymore » is taken into account in an approximation where the distribution function is a function of only the total electron energy. Comparative calculations of the dust particle charge with and without allowance for the nonlocality of the electron energy distribution function have been performed. Allowance for the nonlocality is shown to lead to a noticeable increase in the dust particle charge due to the influence of the group of hot electrons from the tail of the distribution function. It has been established that the screening constant virtually coincides with the smallest screening constant determined according to the asymptotic theory of screening with the electron transport and recombination coefficients in an unperturbed plasma.« less

  16. End-boundary sheath potential, electron and ion energy distribution in the low-pressure non-ambipolar electron plasma

    NASA Astrophysics Data System (ADS)

    Chen, Lee; Chen, Zhiying; Funk, Merritt

    2013-12-01

    The end-boundary floating-surface sheath potential, electron and ion energy distribution functions (EEDf, IEDf) in the low-pressure non-ambipolar electron plasma (NEP) are investigated. The NEP is heated by an electron beam extracted from an inductively coupled electron-source plasma (ICP) through a dielectric injector by an accelerator located inside the NEP. This plasma's EEDf has a Maxwellian bulk followed by a broad energy continuum connecting to the most energetic group with energies around the beam energy. The NEP pressure is 1-3 mTorr of N2 and the ICP pressure is 5-15 mTorr of Ar. The accelerator is biased positively from 80 to 600 V and the ICP power range is 200-300 W. The NEP EEDf and IEDf are determined using a retarding field energy analyser. The EEDf and IEDf are measured at various NEP pressures, ICP pressures and powers as a function of accelerator voltage. The accelerator current and sheath potential are also measured. The IEDf reveals mono-energetic ions with adjustable energy and it is proportionally controlled by the sheath potential. The NEP end-boundary floating surface is bombarded by a mono-energetic, space-charge-neutral plasma beam. When the injected energetic electron beam is adequately damped by the NEP, the sheath potential is linearly controlled at almost a 1 : 1 ratio by the accelerator voltage. If the NEP parameters cannot damp the electron beam sufficiently, leaving an excess amount of electron-beam power deposited on the floating surface, the sheath potential will collapse and become unresponsive to the accelerator voltage.

  17. Targeting Nuclear Factor kappa B for the Treatment of Prostate Cancer

    DTIC Science & Technology

    2005-02-01

    J Immunol 163:5617-23, 1999 3. Mendonca M, Hardacre, M, Datzman, N, Comerford, K, Chin-Sinex, H, Sweeney C.: Inhibition of constitutive NFkappaB ...nuclear factor kappaB activation in 20:7342-51. PC3 cells by genistein is mediated via Akt signaling pathway. Clin 9. Huang S, DeGuzman A, Bucana CD

  18. Diarctigenin, a lignan constituent from Arctium lappa, down-regulated zymosan-induced transcription of inflammatory genes through suppression of DNA binding ability of nuclear factor-kappaB in macrophages.

    PubMed

    Kim, Byung Hak; Hong, Seong Su; Kwon, Soon Woo; Lee, Hwa Young; Sung, Hyeran; Lee, In-Jeong; Hwang, Bang Yeon; Song, Sukgil; Lee, Chong-Kil; Chung, Daehyun; Ahn, Byeongwoo; Nam, Sang-Yoon; Han, Sang-Bae; Kim, Youngsoo

    2008-11-01

    Diarctigenin was previously isolated as an inhibitor of nitric oxide (NO) production in macrophages from the seeds of Arctium lappa used as an alternative medicine for the treatment of inflammatory disorders. However, little is known about the molecular basis of these effects. Here, we demonstrated that diarctigenin inhibited the production of NO, prostaglandin E(2), tumor necrosis factor-alpha, and interleukin (IL)-1beta and IL-6 with IC(50) values of 6 to 12 miciroM in zymosan- or lipopolysaccharide-(LPS) activated macrophages. Diarctigenin attenuated zymosan-induced mRNA synthesis of inducible NO synthase (iNOS) and also inhibited promoter activities of iNOS and cytokine genes in the cells. Because nuclear factor (NF)-kappaB plays a pivotal role in inflammatory gene transcription, we next investigated the effect of diarctigenin on NF-kappaB activation. Diarctigenin inhibited the transcriptional activity and DNA binding ability of NF-kappaB in zymosan-activated macrophages but did not affect the degradation and phosphorylation of inhibitory kappaB (IkappaB) proteins. Moreover, diarctigenin suppressed expression vector NF-kappaB p65-elicited NF-kappaB activation and also iNOS promoter activity, indicating that the compound could directly target an NF-kappa-activating signal cascade downstream of IkappaB degradation and inhibit NF-kappaB-regulated iNOS expression. Diarctigenin also inhibited the in vitro DNA binding ability of NF-kappaB but did not affect the nuclear import of NF-kappaB p65 in the cells. Taken together, diarctigenin down-regulated zymosan- or LPS-induced inflammatory gene transcription in macrophages, which was due to direct inhibition of the DNA binding ability of NF-kappaB. Finally, this study provides a pharmacological potential of diarctigenin in the NF-kappaB-associated inflammatory disorders.

  19. Effect of anomalous electron cross-field transport on electron energy distribution function in a DC-RF magnetized plasma discharge

    NASA Astrophysics Data System (ADS)

    Raitses, Yevgeny; Donnelly, Vincent; Kaganovich, Igor; Godyak, Valery

    2013-09-01

    The application of the magnetic field in a low pressure plasma can cause a spatial separation of cold and hot electron groups. This so-called magnetic filter effect is not well understood and is the subject of our studies. In this work, we investigate electron energy distribution function in a DC-RF plasma discharge with crossed electric and magnetic field operating at sub-mtorr pressure range of xenon gas. Experimental studies showed that the increase of the magnetic field leads to a more uniform profile of the electron temperature across the magnetic field. This surprising result indicates the importance of anomalous electron transport that causes mixing of hot and cold electrons. High-speed imaging and probe measurements revealed a coherent structure rotating in E cross B direction with frequency of a few kHz. Similar to spoke oscillations reported for Hall thrusters, this rotating structure conducts the largest fraction of the cross-field current. This work was supported by the US DOE under Contract DE-AC02-09CH11466.

  20. Rhinovirus stimulation of interleukin-6 in vivo and in vitro. Evidence for nuclear factor kappa B-dependent transcriptional activation.

    PubMed Central

    Zhu, Z; Tang, W; Ray, A; Wu, Y; Einarsson, O; Landry, M L; Gwaltney, J; Elias, J A

    1996-01-01

    To further understand the biology of rhinovirus (RV), we determined whether IL-6 was produced during RV infections and characterized the mechanism by which RV stimulates lung cell IL-6 production. In contrast to normals and minimally symptomatic volunteers, IL-6 was detected in the nasal washings from patients who developed colds after RV challenge. RV14 and RV1A, major and minor receptor group RVs, respectively, were potent stimulators of IL-6 protein production in vitro. These effects were associated with significant increases in IL-6 mRNA accumulation and gene transcription. RV was also a potent stimulator of IL-6 promoter-driven luciferase activity. This stimulation was modestly decreased by mutation of the nuclear factor (NF)-IL-6 site and abrogated by mutation of the NF-kappa B site in this promoter. An NF-kappa B-DNA binding activity, mediated by p65, p50, and p52 NF-kappa B moieties, was rapidly induced in RV-infected cells. Activator protein 1-DNA binding was not similarly altered. These studies demonstrate that IL-6 is produced during symptomatic RV infections, that RVs are potent stimulators of IL-6 elaboration, and that RV stimulation IL-6 production is mediated by an NF-kappa B-dependent transcriptional stimulation pathway. IL-6 may play an important role in the pathogenesis of RV infection, and NF-kappa B activation is likely to be an important event in RV-induced pathologies. PMID:8567963

  1. Few-cycle attosecond pulse chirp effects on asymmetries in ionized electron momentum distributions

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Peng Liangyou; Tan Fang; Gong Qihuang

    2009-07-15

    The momentum distributions of electrons ionized from H atoms by chirped few-cycle attosecond pulses are investigated by numerically solving the time-dependent Schroedinger equation. The central carrier frequency of the pulse is chosen to be 25 eV, which is well above the ionization threshold. The asymmetry (or difference) in the yield of electrons ionized along and opposite to the direction of linear laser polarization is found to be very sensitive to the pulse chirp (for pulses with fixed carrier-envelope phase), both for a fixed electron energy and for the energy-integrated yield. In particular, the larger the pulse chirp, the larger themore » number of times the asymmetry changes sign as a function of ionized electron energy. For a fixed chirp, the ionized electron asymmetry is found to be sensitive also to the carrier-envelope phase of the few-cycle pulse.« less

  2. Thermodynamics reveal that helix four in the NLS of NF-kappaB p65 anchors IkappaBalpha, forming a very stable complex.

    PubMed

    Bergqvist, Simon; Croy, Carrie H; Kjaergaard, Magnus; Huxford, Tom; Ghosh, Gourisankar; Komives, Elizabeth A

    2006-07-07

    IkappaBalpha is an ankyrin repeat protein that inhibits NF-kappaB transcriptional activity by sequestering NF-kappaB outside of the nucleus in resting cells. We have characterized the binding thermodynamics and kinetics of the IkappaBalpha ankyrin repeat domain to NF-kappaB(p50/p65) using surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC). SPR data showed that the IkappaBalpha and NF-kappaB associate rapidly but dissociate very slowly, leading to an extremely stable complex with a K(D,obs) of approximately 40 pM at 37 degrees C. As reported previously, the amino-terminal DNA-binding domain of p65 contributes little to the overall binding affinity. Conversely, helix four of p65, which forms part of the nuclear localization sequence, was essential for high-affinity binding. This was surprising, given the small size of the binding interface formed by this part of p65. The NF-kappaB(p50/p65) heterodimer and p65 homodimer bound IkappaBalpha with almost indistinguishable thermodynamics, except that the NF-kappaB p65 homodimer was characterized by a more favorable DeltaH(obs) relative to the NF-kappaB(p50/p65) heterodimer. Both interactions were characterized by a large negative heat capacity change (DeltaC(P,obs)), approximately half of which was contributed by the p65 helix four that was necessary for tight binding. This could not be accounted for readily by the small loss of buried non-polar surface area and we hypothesize that the observed effect is due to additional folding of some regions of the complex.

  3. Nuclear factor-kappa B decoy suppresses nerve injury and improves mechanical allodynia and thermal hyperalgesia in a rat lumbar disc herniation model.

    PubMed

    Suzuki, Munetaka; Inoue, Gen; Gemba, Takefumi; Watanabe, Tomoko; Ito, Toshinori; Koshi, Takana; Yamauchi, Kazuyo; Yamashita, Masaomi; Orita, Sumihisa; Eguchi, Yawara; Ochiai, Nobuyasu; Kishida, Shunji; Takaso, Masashi; Aoki, Yasuchika; Takahashi, Kazuhisa; Ohtori, Seiji

    2009-07-01

    Nuclear factor-kappa B (NF-kappaB) is a gene transcriptional regulator of inflammatory cytokines. We investigated the transduction efficiency of NF-kappaB decoy to dorsal root ganglion (DRG), as well as the decrease in nerve injury, mechanical allodynia, and thermal hyperalgesia in a rat lumbar disc herniation model. Forty rats were used in this study. NF-kappaB decoy-fluorescein isothiocyanate (FITC) was injected intrathecally at the L5 level in five rats, and its transduction efficiency into DRG measured. In another 30 rats, mechanical pressure was placed on the DRG at the L5 level and nucleus pulposus harvested from the rat coccygeal disc was transplanted on the DRG. Rats were classified into three groups of ten animals each: a herniation + decoy group, a herniation + oligo group, and a herniation only group. For behavioral testing, mechanical allodynia and thermal hyperalgesia were evaluated. In 15 of the herniation rats, their left L5 DRGs were resected, and the expression of activating transcription factor 3 (ATF-3) and calcitonin gene-related peptide (CGRP) was evaluated immunohistochemically compared to five controls. The total transduction efficiency of NF-kappaB decoy-FITC in DRG neurons was 10.8% in vivo. The expression of CGRP and ATF-3 was significantly lower in the herniation + decoy group than in the other herniation groups. Mechanical allodynia and thermal hyperalgesia were significantly suppressed in the herniation + decoy group. NF-kappaB decoy was transduced into DRGs in vivo. NF-kappaB decoy may be useful as a target for clarifying the mechanism of sciatica caused by lumbar disc herniation.

  4. Genes encoding Xenopus laevis Ig L chains: Implications for the evolution of [kappa] and [lambda] chains

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zezza, D.J.; Stewart, S.E.; Steiner, L.A.

    1992-12-15

    Xenopus laevis Ig contain two distinct types of L chains, designated [rho] or L1 and [sigma] or L2. The authors have analyzed Xenopus genomic DNA by Southern blotting with cDNA probes specific for L1 V and C regions. Many fragments hybridized to the V probe, but only one or two fragments hybridized to the C probe. Corresponding C, J, and V gene segments were identified on clones isolated from a genomic library prepared from the same DNA. One clone contains a C gene segment separated from a J gene segment by an intron of 3.4 kb. The J and Cmore » gene segments are nearly identical in sequence to cDNA clones analyzed previously. The C segment is somewhat more similar and the J segment considerably more similar in sequence to the corresponding segments of mammalian [kappa] chains than to those of mammalian [lambda] chains. Upstream of the J segment is a typical recombination signal sequence with a spacer of 23 bp, as in J[kappa]. A second clone from the library contains four V gene segments, separated by 2.1 to 3.6 kb. Two of these, V1 and V3, have the expected structural and regulatory features of V genes, and are very similar in sequence to each other and to mammalian V[kappa]. A third gene segment, V2, resembles V1 and V3 in its coding region and nearby 5[prime]-flanking region, but diverges in sequence 5[prime] to position [minus]95 with loss of the octamer promoter element. The fourth V-like segment is similar to the others at the 3[prime]-end, but upstream of codon 64 bears no resemblance in sequence to any Ig V region. All four V segments have typical recombination signal sequences with 12-bp spacers at their 3[prime]-ends, as in V[kappa]. Taken together, the data suggest that Xenopus L1 L chain genes are members of the [kappa] gene family. 80 refs., 9 figs.« less

  5. Evaluation of NF-kappaB Signaling in T Cells

    DTIC Science & Technology

    2009-01-01

    ranging from myelomas (46) to breast cancer (47) to esophageal cancer (48), to name a few. NF-κB activation is also implicated in several leukemias and...nuclear factor-kappaB/Rel expression and the pathogenesis of breast cancer . J Clin Invest 100:2952-2960. 48. Abdel-Latif, M. M., J. O’Riordan, H. J...42), cyclin D1 (43), and cyclin E (44, 45). Furthermore, NF-κB activity has been linked to the proliferation of various types of cancer cells

  6. Zinc deficiency induces vascular pro-inflammatory parameters associated with NF-kappaB and PPAR signaling.

    PubMed

    Shen, Huiyun; Oesterling, Elizabeth; Stromberg, Arnold; Toborek, Michal; MacDonald, Ruth; Hennig, Bernhard

    2008-10-01

    Marginal intake of dietary zinc can be associated with increased risk of cardiovascular diseases. In the current study we hypothesized that vascular dysfunction and associated inflammatory events are activated during a zinc deficient state. We tested this hypothesis using both vascular endothelial cells and mice lacking the functional LDL-receptor gene. Zinc deficiency increased oxidative stress and NF-kappaB DNA binding activity, and induced COX-2 and E-selectin gene expression, as well as monocyte adhesion in cultured endothelial cells. The NF-kappaB inhibitor CAPE significantly reduced the zinc deficiency-induced COX-2 expression, suggesting regulation through NF-kappaB signaling. PPAR can inhibit NF-kappaB signaling, and our previous data have shown that PPAR transactivation activity requires adequate zinc. Zinc deficiency down-regulated PPARalpha expression in cultured endothelial cells. Furthermore, the PPARgamma agonist rosiglitazone was unable to inhibit the adhesion of monocytes to endothelial cells during zinc deficiency, an event which could be reversed by zinc supplementation. Our in vivo data support the importance of PPAR dysregulation during zinc deficiency. For example, rosiglitazone induced inflammatory genes (e.g., MCP-1) only during zinc deficiency, and adequate zinc was required for rosiglitazone to down-regulate pro-inflammatory markers such as iNOS. In addition, rosiglitazone increased IkappaBalpha protein expression only in zinc adequate mice. Finally, plasma data from LDL-R-deficient mice suggest an overall pro-inflammatory environment during zinc deficiency and support the concept that zinc is required for proper anti-inflammatory or protective functions of PPAR. These studies suggest that zinc nutrition can markedly modulate mechanisms of the pathology of inflammatory diseases such as atherosclerosis.

  7. Head-on collision between positron acoustic waves in homogeneous and inhomogeneous plasmas

    NASA Astrophysics Data System (ADS)

    Alam, M. S.; Hafez, M. G.; Talukder, M. R.; Ali, M. Hossain

    2018-05-01

    The head-on collision between positron acoustic solitary waves (PASWs) as well as the production of rogue waves (RWs) in homogeneous and PASWs in inhomogeneous unmagnetized plasma systems are investigated deriving the nonlinear evolution equations. The plasmas are composed of immobile positive ions, mobile cold and hot positrons, and hot electrons, where the hot positrons and hot electrons are assumed to follow the Kappa distributions. The evolution equations are derived using the appropriate coordinate transformation and the reductive perturbation technique. The effects of concentrations, kappa parameters of hot electrons and positrons, and temperature ratios on the characteristics of PASWs and RWs are examined. It is found that the kappa parameters and temperature ratios significantly modify phase shifts after head-on collisions and RWs in homogeneous as well as PASWs in inhomogeneous plasmas. The amplitudes of the PASWs in inhomogeneous plasmas are diminished with increasing kappa parameters, concentration and temperature ratios. Further, the amplitudes of RWs are reduced with increasing charged particles concentration, while it enhances with increasing kappa- and temperature parameters. Besides, the compressive and rarefactive solitons are produced at critical densities from KdV equation for hot and cold positrons, while the compressive solitons are only produced from mKdV equation for both in homogeneous and inhomogeneous plasmas.

  8. Kappa Opioid Receptors Mediate where Fear Is Expressed Following Extinction Training

    ERIC Educational Resources Information Center

    Cole, Sindy; Richardson, Rick; McNally, Gavan P.

    2011-01-01

    Six experiments used a within-subjects renewal design to examine the involvement of kappa opioid receptors (KORs) in regulating the expression and recovery of extinguished fear. Rats were trained to fear a tone conditioned stimulus (CS) via pairings with foot shock in a distinctive context (A). This was followed by extinction training of the CS in…

  9. Inhibition by antioxidants of nitric oxide synthase expression in murine macrophages: role of nuclear factor kappa B and interferon regulatory factor 1.

    PubMed Central

    Hecker, M.; Preiss, C.; Klemm, P.; Busse, R.

    1996-01-01

    1. In view of the potential deleterious effects of high amounts of nitric oxide (NO) produced by the inducible isoform of NO synthase (iNOS) in inflammation, the prevention of the expression of this enzyme represents an important therapeutic goal. In cytokine-stimulated cells, activation of nuclear factor kappa B (NF-kappa B) is crucial for the increase in iNOS gene expression. Since NF-kappa B activation appears to involve a redox-sensitive step, we have investigated whether three structurally unrelated antioxidants, 5,7-dihydroxyflavone (chrysin), 3,4-dichloroisocoumarin (DCI) and N-acetyl 5-hydroxytryptamine (N-acetylserotonin, NAS), affect iNOS expression in cultured RAW 264.7 monocyte/macrophages stimulated with bacterial lipopolysaccharide (LPS, 140 ng ml-1) and interferon-gamma (IFN gamma, 5 u ml-1). 2. During a 6 h incubation period neither LPS nor IFN gamma alone exerted a significant effect but when combined, caused a prominent increase in nitrite formation, iNOS mRNA and protein abundance. Co-incubation with chrysin (50 microM), DCI (50 microM) or NAS (1 mM) markedly attenuated this increase in iNOS gene expression. 3. DCI, but not chrysin or NAS, prevented the activation of NF-kappa B in cells exposed to LPS plus IFN gamma for 30 min. In contrast, all three antioxidants significantly blunted the DNA-binding activity of interferon regulatory factor 1 (IRF-1), which mediates the synergistic effect of IFN gamma on iNOS gene expression in cells treated for 2 h with LPS plus IFN gamma. 4. DCI thus appears to inhibit iNOS gene expression at the transcriptional level by preventing the activation of both NF-kappa B and IRF-1. The inhibitory effect of DCI on NF-kappa B activation, however, does not seem to be related to its antioxidative properties, since DCI, unlike chrysin or NAS, is a potent serine protease inhibitor which stabilizes the inactive NF-kappa B complex by protecting the inhibitory I kappa B-alpha subunit from proteolytic degradation. 5. The

  10. PIC simulations of wave-particle interactions with an initial electron velocity distribution from a kinetic ring current model

    DOE PAGES

    Yu, Yiqun; Delzanno, Gian Luca; Jordanova, Vania Koleva; ...

    2017-07-15

    Whistler wave-particle interactions play an important role in the Earth inner magnetospheric dynamics and have been the subject of numerous investigations. By running a global kinetic ring current model (RAM-SCB) in a storm event occurred on Oct 23–24 2002, we obtain the ring current electron distribution at a selected location at MLT of 9 and L of 6 where the electron distribution is composed of a warm population in the form of a partial ring in the velocity space (with energy around 15 keV) in addition to a cool population with a Maxwellian-like distribution. The warm population is likely frommore » the injected plasma sheet electrons during substorm injections that supply fresh source to the inner magnetosphere. These electron distributions are then used as input in an implicit particle-in-cell code (iPIC3D) to study whistler-wave generation and the subsequent wave-particle interactions. Here, we find that whistler waves are excited and propagate in the quasi-parallel direction along the background magnetic field. Several different wave modes are instantaneously generated with different growth rates and frequencies. The wave mode at the maximum growth rate has a frequency around 0.62ω ce, which corresponds to a parallel resonant energy of 2.5 keV. Linear theory analysis of wave growth is in excellent agreement with the simulation results. These waves grow initially due to the injected warm electrons and are later damped due to cyclotron absorption by electrons whose energy is close to the resonant energy and can effectively attenuate waves. The warm electron population overall experiences net energy loss and anisotropy drop while moving along the diffusion surfaces towards regions of lower phase space density, while the cool electron population undergoes heating when the waves grow, suggesting the cross-population interactions.« less

  11. PIC simulations of wave-particle interactions with an initial electron velocity distribution from a kinetic ring current model

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yu, Yiqun; Delzanno, Gian Luca; Jordanova, Vania Koleva

    Whistler wave-particle interactions play an important role in the Earth inner magnetospheric dynamics and have been the subject of numerous investigations. By running a global kinetic ring current model (RAM-SCB) in a storm event occurred on Oct 23–24 2002, we obtain the ring current electron distribution at a selected location at MLT of 9 and L of 6 where the electron distribution is composed of a warm population in the form of a partial ring in the velocity space (with energy around 15 keV) in addition to a cool population with a Maxwellian-like distribution. The warm population is likely frommore » the injected plasma sheet electrons during substorm injections that supply fresh source to the inner magnetosphere. These electron distributions are then used as input in an implicit particle-in-cell code (iPIC3D) to study whistler-wave generation and the subsequent wave-particle interactions. Here, we find that whistler waves are excited and propagate in the quasi-parallel direction along the background magnetic field. Several different wave modes are instantaneously generated with different growth rates and frequencies. The wave mode at the maximum growth rate has a frequency around 0.62ω ce, which corresponds to a parallel resonant energy of 2.5 keV. Linear theory analysis of wave growth is in excellent agreement with the simulation results. These waves grow initially due to the injected warm electrons and are later damped due to cyclotron absorption by electrons whose energy is close to the resonant energy and can effectively attenuate waves. The warm electron population overall experiences net energy loss and anisotropy drop while moving along the diffusion surfaces towards regions of lower phase space density, while the cool electron population undergoes heating when the waves grow, suggesting the cross-population interactions.« less

  12. Structure-activity relationship studies of chalcone leading to 3-hydroxy-4,3',4',5'-tetramethoxychalcone and its analogues as potent nuclear factor kappaB inhibitors and their anticancer activities.

    PubMed

    Srinivasan, Balasubramanian; Johnson, Thomas E; Lad, Rahul; Xing, Chengguo

    2009-11-26

    Chalcone is a privileged structure, demonstrating promising anti-inflammatory and anticancer activities. One potential mechanism is to suppress nuclear factor kappa B (NF-kappaB) activation. The structures of chalcone-based NF-kappaB inhibitors vary significantly that there is minimum information about their structure-activity relationships (SAR). This study aims to establish SAR of chalcone-based compounds to NF-kappaB inhibition, to explore the feasibility of developing simple chalcone-based potent NF-kappaB inhibitors, and to evaluate their anticancer activities. Three series of chalcones were synthesized in one to three steps with the key step being aldol condensation. These candidates demonstrated a wide range of NF-kappaB inhibitory activities, some of low micromolar potency, establishing that structural complexity is not required for NF-kappaB inhibition. Lead compounds also demonstrate potent cytotoxicity against lung cancer cells. Their cytotoxicities correlate moderately well with their NF-kappaB inhibitory activities, suggesting that suppressing NF-kappaB activation is likely responsible for at least some of the cytotoxicities. One lead compound effectively inhibits lung tumor growth with no signs of adverse side effects.

  13. First spin-resolved electron distributions in crystals from combined polarized neutron and X-ray diffraction experiments.

    PubMed

    Deutsch, Maxime; Gillon, Béatrice; Claiser, Nicolas; Gillet, Jean-Michel; Lecomte, Claude; Souhassou, Mohamed

    2014-05-01

    Since the 1980s it has been possible to probe crystallized matter, thanks to X-ray or neutron scattering techniques, to obtain an accurate charge density or spin distribution at the atomic scale. Despite the description of the same physical quantity (electron density) and tremendous development of sources, detectors, data treatment software etc., these different techniques evolved separately with one model per experiment. However, a breakthrough was recently made by the development of a common model in order to combine information coming from all these different experiments. Here we report the first experimental determination of spin-resolved electron density obtained by a combined treatment of X-ray, neutron and polarized neutron diffraction data. These experimental spin up and spin down densities compare very well with density functional theory (DFT) calculations and also confirm a theoretical prediction made in 1985 which claims that majority spin electrons should have a more contracted distribution around the nucleus than minority spin electrons. Topological analysis of the resulting experimental spin-resolved electron density is also briefly discussed.

  14. Evaluation of an imputed pitch velocity model of the auditory kappa effect.

    PubMed

    Henry, Molly J; McAuley, J Devin

    2009-04-01

    Three experiments evaluated an imputed pitch velocity model of the auditory kappa effect. Listeners heard 3-tone sequences and judged the timing of the middle (target) tone relative to the timing of the 1st and 3rd (bounding) tones. Experiment 1 held pitch constant but varied the time (T) interval between bounding tones (T = 728, 1,000, or 1,600 ms) in order to establish baseline performance levels for the 3 values of T. Experiments 2 and 3 combined the values of T tested in Experiment 1 with a pitch manipulation in order to create fast (8 semitones/728 ms), medium (8 semitones/1,000 ms), and slow (8 semitones/1,600 ms) velocity conditions. Consistent with an auditory motion hypothesis, distortions in perceived timing were larger for fast than for slow velocity conditions for both ascending sequences (Experiment 2) and descending sequences (Experiment 3). Overall, results supported the proposed imputed pitch velocity model of the auditory kappa effect. (c) 2009 APA, all rights reserved.

  15. Molecular genetic analysis of the V kappa Ser group associated with two mouse light chain genetic markers. Complementary DNA cloning and southern hybridization analysis

    PubMed Central

    1985-01-01

    Previous studies (21) have shown that two mouse kappa light (L) chain variable (V) region polymorphisms, the IB-peptide and Efla markers, reflect expression of a characteristic group of V kappa regions, called V kappa Ser, by some inbred strains and not others. Expression of V kappa Ser is controlled by a locus on chromosome 6, the chromosome that contains the kappa locus. To further characterize this V kappa group and begin to analyze the basis for its strain-specific expression, full- length complementary DNA (cDNA) copies were produced of L chain mRNA from the M75 myeloma that had been induced in the C.C58 strain of mice, and which produces a V kappa Ser L chain. The C.C58 strain is congenic with BALB/cAn, differing in the region of chromosome 6 that controls expression of the V kappa polymorphisms and the Lyt-2 and Lyt-3 T cell alloantigens. The complete nucleotide sequence of this cloned cDNA was determined and compared with the nucleotide sequences the most closely related BALB/c myeloma L chains known. Results indicated significant differences throughout the variable region, but particularly toward the 5' portion of the sequence. A probe corresponding to 200 bp of the 5' end of the cloned V kappa Ser cDNA was used in Southern hybridizations of restriction digests of liver DNA from a number of inbred, recombinant, and recombinant inbred strains. Under stringent hybridization conditions, one strongly-hybridizing fragment was observed in Bam HI, Hind III, and Eco RI digests, and based on the size of the fragments, strains could be organized into two groups. The presence of strongly hybridizing Bam HI, Hind III, and Eco RI fragments of 3.2, 2.8, and 2.1 kb, respectively, was found to correlate completely with expression by the strain of the IB-peptide and Efla markers. All nonexpressor strains yielded hybridizing fragments of 7.8, 8.4, and 2.8 kb, respectively. Possible explanations for strain- specific expression of V kappa Ser-associated phenotypic markers are

  16. Inhibitory effect on activator protein-1, nuclear factor-kappaB, and cell transformation by extracts of strawberries (Fragaria x ananassa Duch.).

    PubMed

    Wang, Shiow Y; Feng, Rentian; Lu, Yongju; Bowman, Linda; Ding, Min

    2005-05-18

    The inhibitory effects of strawberry (Fragaria x ananassa Duch.) antioxidant enzymes on tetradecanoylphorbol-13-acetate (TPA) or ultraviolet-B (UVB) induced activator protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB) were studied. The inhibitory effects of strawberry extracts on the proliferation and transformation of human and mouse cancer cells were also evaluated. Strawberries had high activities of glutathione peroxidase, superoxide dismutase, guaiacol peroxidase, ascorbate peroxidase, and glutathione reductase. Strawberry extracts inhibited the proliferation of human lung epithelial cancer cell line A549 and decreased TPA-induced neoplastic transformation of JB6 P+ mouse epidermal cells. Pretreatment of JB6 P+ mouse epidermal cells with strawberry extract resulted in the inhibition of both UVB- and TPA-induced AP-1 and NF-kappaB transactivation. Furthermore, strawberry extract also blocked TPA-induced phosphorylation of extracellular signal-regulated kinases (ERKs) and UVB-induced phosphorylation of ERKs and JNK kinase in JB6 P+ mouse epidermal cell culture. These results suggest that the ability of strawberries to block UVB- and TPA-induced AP-1 and NF-kappaB activation may be due to their antioxidant properties and their ability to reduce oxidative stress. The oxidative events that regulate AP-1 and NF-kappaB transactivation can be important molecular targets for cancer prevention. The strawberries may be highly effective as a chemopreventive agent that acts by targeting the down-regulation of AP-1 and NF-kappaB activities, blocking MAPK signaling, and suppressing cancer cell proliferation and transformation.

  17. Synthesis and characterization of a dual kappa-delta opioid receptor agonist analgesic blocking cocaine reward behavior.

    PubMed

    Váradi, András; Marrone, Gina F; Eans, Shainnel O; Ganno, Michelle L; Subrath, Joan J; Le Rouzic, Valerie; Hunkele, Amanda; Pasternak, Gavril W; McLaughlin, Jay P; Majumdar, Susruta

    2015-11-18

    3-Iodobenzoyl naltrexamine (IBNtxA) is a potent analgesic belonging to the pharmacologically diverse 6β-amidoepoxymorphinan group of opioids. We present the synthesis and pharmacological evaluation of five analogs of IBNtxA. The scaffold of IBNtxA was modified by removing the 14-hydroxy group, incorporating a 7,8 double bond and various N-17 alkyl substituents. The structural modifications resulted in analogs with picomolar affinities for opioid receptors. The lead compound (MP1104) was found to exhibit approximately 15-fold greater antinociceptive potency (ED50 = 0.33 mg/kg) compared with morphine, mediated through the activation of kappa- and delta-opioid receptors. Despite its kappa agonism, this lead derivative did not cause place aversion or preference in mice in a place-conditioning assay, even at doses 3 times the analgesic ED50. However, pretreatment with the lead compound prevented the reward behavior associated with cocaine in a conditioned place preference assay. Together, these results suggest the promise of dual acting kappa- and delta-opioid receptor agonists as analgesics and treatments for cocaine addiction.

  18. Modeling Electronic Skin Response to Normal Distributed Force.

    PubMed

    Seminara, Lucia

    2018-02-03

    The reference electronic skin is a sensor array based on PVDF (Polyvinylidene fluoride) piezoelectric polymers, coupled to a rigid substrate and covered by an elastomer layer. It is first evaluated how a distributed normal force (Hertzian distribution) is transmitted to an extended PVDF sensor through the elastomer layer. A simplified approach based on Boussinesq's half-space assumption is used to get a qualitative picture and extensive FEM simulations allow determination of the quantitative response for the actual finite elastomer layer. The ultimate use of the present model is to estimate the electrical sensor output from a measure of a basic mechanical action at the skin surface. However this requires that the PVDF piezoelectric coefficient be known a-priori. This was not the case in the present investigation. However, the numerical model has been used to fit experimental data from a real skin prototype and to estimate the sensor piezoelectric coefficient. It turned out that this value depends on the preload and decreases as a result of PVDF aging and fatigue. This framework contains all the fundamental ingredients of a fully predictive model, suggesting a number of future developments potentially useful for skin design and validation of the fabrication technology.

  19. Research on distributed virtual reality system in electronic commerce

    NASA Astrophysics Data System (ADS)

    Xue, Qiang; Wang, Jiening; Sun, Jizhou

    2004-03-01

    In this paper, Distributed Virtual Reality (DVR) technology applied in Electronical Commerce (EC) is discussed. DVR has the capability of providing a new means for human being to recognize, analyze and resolve the large scale, complex problems, which makes it develop quickly in EC fields. The technology of CSCW (Computer Supported Cooperative Work) and middleware is introduced into the development of EC-DVR system to meet the need of a platform which can provide the necessary cooperation and communication services to avoid developing the basic module repeatedly. Finally, the paper gives a platform structure of EC-DVR system.

  20. FLICE-like inhibitory protein (FLIP) protects against apoptosis and suppresses NF-kappaB activation induced by bacterial lipopolysaccharide.

    PubMed

    Bannerman, Douglas D; Eiting, Kristine T; Winn, Robert K; Harlan, John M

    2004-10-01

    Bacterial lipopolysaccharide (LPS) via its activation of Toll-like receptor-4 contributes to much of the vascular injury/dysfunction associated with gram-negative sepsis. Inhibition of de novo gene expression has been shown to sensitize endothelial cells (EC) to LPS-induced apoptosis, the onset of which correlates with decreased expression of FLICE-like inhibitory protein (FLIP). We now have data that conclusively establish a role for FLIP in protecting EC against LPS-induced apoptosis. Overexpression of FLIP protected against LPS-induced apoptosis, whereas down-regulation of FLIP using antisense oligonucleotides sensitized EC to direct LPS killing. Interestingly, FLIP overexpression suppressed NF-kappaB activation induced by LPS, but not by phorbol ester, suggesting a specific role for FLIP in mediating LPS activation. Conversely, mouse embryo fibroblasts (MEF) obtained from FLIP -/- mice showed enhanced LPS-induced NF-kappaB activation relative to those obtained from wild-type mice. Reconstitution of FLIP-/- MEF with full-length FLIP reversed the enhanced NF-kappaB activity elicited by LPS in the FLIP -/- cells. Changes in the expression of FLIP had no demonstrable effect on other known LPS/Tlr-4-activated signaling pathways including the p38, Akt, and Jnk pathways. Together, these data support a dual role for FLIP in mediating LPS-induced apoptosis and NF-kappaB activation.