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.

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.

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.

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

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

Dispersion relations for 1D high-gain FELs

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

Webb, S.D.; Litvinenko, V.N.

2010-08-23

We present analytical results for the one-dimensional dispersion relation for high-gain FELs. Using kappa-n distributions, we obtain analytical relations between the dispersion relations for various order kappa distributions. Since an exact solution exists for the kappa-1 (Lorentzian) distribution, this provides some insight into the number of modes on the way to the Gaussian distribution.

Statistical mechanics in the context of special relativity.

PubMed

Kaniadakis, G

2002-11-01

In Ref. [Physica A 296, 405 (2001)], starting from the one parameter deformation of the exponential function exp(kappa)(x)=(sqrt[1+kappa(2)x(2)]+kappax)(1/kappa), a statistical mechanics has been constructed which reduces to the ordinary Boltzmann-Gibbs statistical mechanics as the deformation parameter kappa approaches to zero. The distribution f=exp(kappa)(-beta E+betamu) obtained within this statistical mechanics shows a power law tail and depends on the nonspecified parameter beta, containing all the information about the temperature of the system. On the other hand, the entropic form S(kappa)= integral d(3)p(c(kappa) f(1+kappa)+c(-kappa) f(1-kappa)), which after maximization produces the distribution f and reduces to the standard Boltzmann-Shannon entropy S0 as kappa-->0, contains the coefficient c(kappa) whose expression involves, beside the Boltzmann constant, another nonspecified parameter alpha. In the present effort we show that S(kappa) is the unique existing entropy obtained by a continuous deformation of S0 and preserving unaltered its fundamental properties of concavity, additivity, and extensivity. These properties of S(kappa) permit to determine unequivocally the values of the above mentioned parameters beta and alpha. Subsequently, we explain the origin of the deformation mechanism introduced by kappa and show that this deformation emerges naturally within the Einstein special relativity. Furthermore, we extend the theory in order to treat statistical systems in a time dependent and relativistic context. Then, we show that it is possible to determine in a self consistent scheme within the special relativity the values of the free parameter kappa which results to depend on the light speed c and reduces to zero as c--> infinity recovering in this way the ordinary statistical mechanics and thermodynamics. The statistical mechanics here presented, does not contain free parameters, preserves unaltered the mathematical and epistemological structure of the ordinary statistical mechanics and is suitable to describe a very large class of experimentally observed phenomena in low and high energy physics and in natural, economic, and social sciences. Finally, in order to test the correctness and predictability of the theory, as working example we consider the cosmic rays spectrum, which spans 13 decades in energy and 33 decades in flux, finding a high quality agreement between our predictions and observed data.

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.

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.;

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.

Quasi-electrostatic twisted waves in Lorentzian dusty plasmas

NASA Astrophysics Data System (ADS)

Arshad, Kashif; Lazar, M.; Poedts, S.

2018-07-01

The quasi electrostatic modes are investigated in non thermal dusty plasma using non-gyrotropic Kappa distribution in the presence of helical electric field. The Laguerre Gaussian (LG) mode function is employed to decompose the perturbed distribution function and helical electric field. The modified dielectric function is obtained for the dust ion acoustic (DIA) and dust acoustic (DA) twisted modes from the solution of Vlasov-Poisson equation. The threshold conditions for the growing modes is also illustrated.

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.

Kinetic Theory of quasi-electrostatic waves in non-gyrotropic plasmas

NASA Astrophysics Data System (ADS)

Arshad, K.; Poedts, S.; Lazar, M.

2017-12-01

The orbital angular momentum (OAM) is a trait of helically phased light or helical (twisted) electric field. Lasers carrying orbital angular momentum (OAM) revolutionized many scientific and technological paradigms like microscopy, imaging and ionospheric radar facility to analyze three dimensional plasma dynamics in ionosphere, ultra-intense twisted laser pulses, twisted gravitational waves and astrophysics. This trend has also been investigated in plasma physics. Laguerre-Gaussian type solutions are predicted for magnetic tornadoes and Alfvénic tornadoes which exhibit spiral, split and ring-like morphologies. The ring shape morphology is ideal to fit the observed solar corona, solar atmosphere and Earth's ionosphere. The orbital angular momentum indicates the mediation of electrostatic and electromagnetic waves in new phenomena like Raman and Brillouin scattering. A few years ago, some new effects have been included in studies of orbital angular momentum in plasma regimes such as wave-particle interaction in the presence of helical electric field. Therefore, kinetic studies are carried out to investigate the Landau damping of the waves and growth of the instabilities in the presence helical electric field carrying orbital angular momentum for the Maxwellian distributed plasmas. Recently, a well suited approach involving a kappa distribution function has been adopted to model the twisted space plasmas. This leads to the development of new theoretical grounds for the study of Lorentzian or kappa distributed twisted Langmuir, ion acoustic, dust ion acoustic and dust acoustic modes. The quasi-electrostatic twisted waves have been studied now for the non-gyrotropic dusty plasmas in the presence of the orbital angular momentum of the helical electric field using Generalized Lorentzian or kappa distribution function. The Laguerre-Gaussian (LG) mode function is employed to decompose the perturbed distribution function and electric field into planar (longitudinal) and non-planar (azimuthal) components. The modified Vlasov and Poisson equations are solved to obtain the dielectric function for quasi-electrostatic twisted modes the non-gyrotropic dusty plasmas. Some numerical and graphical analysis is also illustrated for the better understanding of the twisted non-gyrotropic plasmas.

Statistical characteristics of storm interevent time, depth, and duration for eastern New Mexico, Oklahoma, and Texas

USGS Publications Warehouse

Asquith, William H.; Roussel, Meghan C.; Cleveland, Theodore G.; Fang, Xing; Thompson, David B.

2006-01-01

The design of small runoff-control structures, from simple floodwater-detention basins to sophisticated best-management practices, requires the statistical characterization of rainfall as a basis for cost-effective, risk-mitigated, hydrologic engineering design. The U.S. Geological Survey, in cooperation with the Texas Department of Transportation, has developed a framework to estimate storm statistics including storm interevent times, distributions of storm depths, and distributions of storm durations for eastern New Mexico, Oklahoma, and Texas. The analysis is based on hourly rainfall recorded by the National Weather Service. The database contains more than 155 million hourly values from 774 stations in the study area. Seven sets of maps depicting ranges of mean storm interevent time, mean storm depth, and mean storm duration, by county, as well as tables listing each of those statistics, by county, were developed. The mean storm interevent time is used in probabilistic models to assess the frequency distribution of storms. The Poisson distribution is suggested to model the distribution of storm occurrence, and the exponential distribution is suggested to model the distribution of storm interevent times. The four-parameter kappa distribution is judged as an appropriate distribution for modeling the distribution of both storm depth and storm duration. Preference for the kappa distribution is based on interpretation of L-moment diagrams. Parameter estimates for the kappa distributions are provided. Separate dimensionless frequency curves for storm depth and duration are defined for eastern New Mexico, Oklahoma, and Texas. Dimension is restored by multiplying curve ordinates by the mean storm depth or mean storm duration to produce quantile functions of storm depth and duration. Minimum interevent time and location have slight influence on the scale and shape of the dimensionless frequency curves. Ten example problems and solutions to possible applications are provided.

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.

Maximum Renyi entropy principle for systems with power-law Hamiltonians.

PubMed

Bashkirov, A G

2004-09-24

The Renyi distribution ensuring the maximum of Renyi entropy is investigated for a particular case of a power-law Hamiltonian. Both Lagrange parameters alpha and beta can be eliminated. It is found that beta does not depend on a Renyi parameter q and can be expressed in terms of an exponent kappa of the power-law Hamiltonian and an average energy U. The Renyi entropy for the resulting Renyi distribution reaches its maximal value at q=1/(1+kappa) that can be considered as the most probable value of q when we have no additional information on the behavior of the stochastic process. The Renyi distribution for such q becomes a power-law distribution with the exponent -(kappa+1). When q=1/(1+kappa)+epsilon (0

Persistence length changes dramatically as RNA folds.

PubMed

Caliskan, G; Hyeon, C; Perez-Salas, U; Briber, R M; Woodson, S A; Thirumalai, D

2005-12-31

We determine the persistence length l(p) for a bacterial group I ribozyme as a function of concentration of monovalent and divalent cations by fitting the distance distribution functions P(r) obtained from small angle x-ray scattering intensity data to the asymptotic form of the calculated P(WLC)(r) for a wormlike chain. The l(p) values change dramatically over a narrow range of Mg(2+) concentration from approximately 21 Angstroms in the unfolded state (U) to approximately 10 Angstroms in the compact (I(C)) and native states. Variations in l(p) with increasing Na(+) concentration are more gradual. In accord with the predictions of polyelectrolyte theory we find l(p) alpha 1/kappa(2) where kappa is the inverse Debye-screening length.

The energetic ion signature of an O-type neutral line in the geomagnetic tail

NASA Technical Reports Server (NTRS)

Martin, R. F., Jr.; Johnson, D. F.; Speiser, T. W.

1991-01-01

An energetic ion signature is presented which has the potential for remote sensing of an O-type neutral line embedded in a current sheet. A source plasma with a tailward flowing Kappa distribution yields a strongly non-Kappa distribution after interacting with the neutral line: sharp jumps, or ridges, occur in the velocity space distribution function f(nu-perpendicular, nu-parallel) associated with both increases and decreases in f. The jumps occur when orbits are reversed in the x-direction: a reversal causing initially earthward particles (low probability in the source distribution) to be observed results in a decrease in f, while a reversal causing initially tailward particles to be observed produces an increase in f. The reversals, and hence the jumps, occur at approximately constant values of perpendicular velocity in both the positive nu parallel and negative nu parallel half planes. The results were obtained using single particle simulations in a fixed magnetic field model.

Observations of thermal and suprathermal tail ions from WIND

NASA Astrophysics Data System (ADS)

Randol, B. M.; Christian, E. R.; Wilson, L. B., III

2016-12-01

The velocity distribution function (VDF) of solar wind protons (as well as other ion populations) is comprised of a thermal Maxwellian core and an accelerated suprathermal tail, beginning at around 1 keV in the frame co-moving with solar wind bulk velocity. The form of the suprathermal tail is a power law in phase space density, f, vs. speed, v, such that f / vγ, where γ is the power law index. This commonly observed index is of particular interest because no traditional theory predicts its existence. We need more data in order to test these theories. The general shape is of interest because it is kappa-like. We show combined observations from three different instruments on the WIND spacecraft: 3DP/PLSP, STICS, and 3DP/SST/Open. These data stretch from 102 to 107 eV in energy, encompassing both the thermal and suprathermal proton populations. We show further evidence for this kappa-like distribution and report on our progress on fitting of empirical functions to these data.

Particle velocity distribution in a three-dimensional dusty plasma under microgravity conditions

NASA Astrophysics Data System (ADS)

Liu, Bin; Goree, J.; Pustylnik, M. Y.; Thomas, H. M.; Fortov, V. E.; Lipaev, A. M.; Usachev, A. D.; Molotkov, V. I.; Petrov, O. F.; Thoma, M. H.

2018-01-01

The velocity distribution function of dust particles immersed in a plasma was investigated under microgravity conditions. A three-dimensional (3D) cloud of polymer microspheres was suspended in a neon plasma, in the PK-4 instrument onboard the International Space Station (ISS). These dust particles were tracked using video microscopy in a cross section of the 3D dust cloud. The velocity distribution function (VDF) is found to have a non-Maxwellian shape with high-energy tails; it is fit well by a combination of low-energy Maxwellian core and a high-energy non-Gaussian Kappa-distribution halo. Similar non-Maxwellian VDFs are typically observed in space plasmas.

BZLF1, an Epstein-Barr virus immediate-early protein, induces p65 nuclear translocation while inhibiting p65 transcriptional function

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

Morrison, Thomas E.; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; Kenney, Shannon C.

We have previously demonstrated that the Epstein-Barr virus immediate-early BZLF1 protein interacts with, and is inhibited by, the NF-{kappa}B family member p65. However, the effects of BZLF1 on NF-{kappa}B activity have not been intensively studied. Here we show that BZLF1 inhibits p65-dependent gene expression. BZLF1 inhibited the ability of IL-1, as well as transfected p65, to activate the expression of two different NF-{kappa}B-responsive genes, ICAM-1 and I{kappa}B-{alpha}. BZLF1 also reduced the constitutive level of I{kappa}B-{alpha} protein in HeLa and A549 cells, and increased the amount of nuclear NF-{kappa}B to a similar extent as tumor necrosis factor-alpha (TNF-{alpha}) treatment. In spitemore » of this BZLF1-associated increase in the nuclear form of NF-{kappa}B, BZLF1 did not induce binding of NF-{kappa}B to NF-{kappa}B responsive promoters (as determined by chromatin immunoprecipitation assay) in vivo, although TNF-{alpha} treatment induced NF-{kappa}B binding as expected. Overexpression of p65 dramatically inhibited the lytic replication cycle of EBV in 293-EBV cells, confirming that NF-{kappa}B also inhibits BZLF1 transcriptional function. Our results are consistent with a model in which BZLF1 inhibits the transcriptional function of p65, resulting in decreased transcription of I{kappa}B-{alpha}, decreased expression of I{kappa}B-{alpha} protein, and subsequent translocation of NF-{kappa}B to the nucleus. This nuclear translocation of NF-{kappa}B may promote viral latency by negatively regulating BZLF1 transcriptional activity. In situations where p65 activity is limiting in comparison to BZLF1, the ability of BZLF1 to inhibit p65 transcriptional function may protect the virus from the host immune system during the lytic form of infection.« less

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

IMPROVING THE PRECISION OF TIME-DELAY COSMOGRAPHY WITH OBSERVATIONS OF GALAXIES ALONG THE LINE OF SIGHT

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

Greene, Zach S.; Suyu, Sherry H.; Treu, Tommaso

2013-05-01

In order to use strong gravitational lens time delays to measure precise and accurate cosmological parameters the effects of mass along the line of sight must be taken into account. We present a method to achieve this by constraining the probability distribution function of the effective line-of-sight convergence {kappa}{sub ext}. The method is based on matching the observed overdensity in the weighted number of galaxies to that found in mock catalogs with {kappa}{sub ext} obtained by ray-tracing through structure formation simulations. We explore weighting schemes based on projected distance, mass, luminosity, and redshift. This additional information reduces the uncertainty ofmore » {kappa}{sub ext} from {sigma}{sub {kappa}} {approx} 0.06 to {approx}0.04 for very overdense LOSs like that of the system B1608+656. For more common LOSs, {sigma}{sub {kappa}} is reduced to {approx}<0.03, corresponding to an uncertainty of {approx}< 3% on distance. This uncertainty has comparable effects on cosmological parameters to that arising from the mass model of the deflector and its immediate environment. Photometric redshifts based on g, r, i and K photometries are sufficient to constrain {kappa}{sub ext} almost as well as with spectroscopic redshifts. As an illustration, we apply our method to the system B1608+656. Our most reliable {kappa}{sub ext} estimator gives {sigma}{sub {kappa}} = 0.047 down from 0.065 using only galaxy counts. Although deeper multiband observations of the field of B1608+656 are necessary to obtain a more precise estimate, we conclude that griK photometry, in addition to spectroscopy to characterize the immediate environment, is an effective way to increase the precision of time-delay cosmography.« less

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.

Testing the lognormality of the galaxy and weak lensing convergence distributions from Dark Energy Survey maps

DOE PAGES

Clerkin, L.; Kirk, D.; Manera, M.; ...

2016-08-30

It is well known that the probability distribution function (PDF) of galaxy density contrast is approximately lognormal; whether the PDF of mass fluctuations derived from weak lensing convergence (kappa_WL) is lognormal is less well established. We derive PDFs of the galaxy and projected matter density distributions via the Counts in Cells (CiC) method. We use maps of galaxies and weak lensing convergence produced from the Dark Energy Survey (DES) Science Verification data over 139 deg^2. We test whether the underlying density contrast is well described by a lognormal distribution for the galaxies, the convergence and their joint PDF. We confirmmore » that the galaxy density contrast distribution is well modeled by a lognormal PDF convolved with Poisson noise at angular scales from 10-40 arcmin (corresponding to physical scales of 3-10 Mpc). We note that as kappa_WL is a weighted sum of the mass fluctuations along the line of sight, its PDF is expected to be only approximately lognormal. We find that the kappa_WL distribution is well modeled by a lognormal PDF convolved with Gaussian shape noise at scales between 10 and 20 arcmin, with a best-fit chi^2/DOF of 1.11 compared to 1.84 for a Gaussian model, corresponding to p-values 0.35 and 0.07 respectively, at a scale of 10 arcmin. Above 20 arcmin a simple Gaussian model is sufficient. The joint PDF is also reasonably fitted by a bivariate lognormal. As a consistency check we compare the variances derived from the lognormal modelling with those directly measured via CiC. Our methods are validated against maps from the MICE Grand Challenge N-body simulation.« less

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.

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

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).

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 approach to allow for kappa distributions instead. While this introduces an additional degree of freedom and therefore requires fitting, our approach is still better constrained than the traditional Maxwell fitting and may hold the key to a better understanding of the true nature of plasmaspheric particle distributions.

Comparison of the King's and MiToS staging systems for ALS.

PubMed

Fang, Ton; Al Khleifat, Ahmad; Stahl, Daniel R; Lazo La Torre, Claudia; Murphy, Caroline; Young, Carolyn; Shaw, Pamela J; Leigh, P Nigel; Al-Chalabi, Ammar

2017-05-01

To investigate and compare two ALS staging systems, King's clinical staging and Milano-Torino (MiToS) functional staging, using data from the LiCALS phase III clinical trial (EudraCT 2008-006891-31). Disease stage was derived retrospectively for each system from the ALS Functional Rating Scale-Revised subscores using standard methods. The two staging methods were then compared for timing of stages using box plots, correspondence using chi-square tests, agreement using a linearly weighted kappa coefficient and concordance using Spearman's rank correlation. For both systems, progressively higher stages occurred at progressively later proportions of the disease course, but the distribution differed between the two methods. King's stage 3 corresponded to MiToS stage 1 most frequently, with earlier King's stages 1 and 2 largely corresponding to MiToS stage 0 or 1. The Spearman correlation was 0.54. There was fair agreement between the two systems with kappa coefficient of 0.21. The distribution of timings shows that the two systems are complementary, with King's staging showing greatest resolution in early to mid-disease corresponding to clinical or disease burden, and MiToS staging having higher resolution for late disease, corresponding to functional involvement. We therefore propose using both staging systems when describing ALS.

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

Jomary, C.; Beaudet, A.; Gairin, J.E.

Distribution of {kappa} opioid receptors was examined by EM radioautography in sections of guinea pig neostriatum with the selective {sup 125}I-labeled dynorphin analog (D-Pro{sup 10})dynorphin-(1-11). Most specifically labeled binding sites were found by probability circle analysis to be associated with neuronal membrane appositions. Because of limitations in resolution of the method, the radioactive sources could not be ascribed directly to either one of the apposed plasma membranes. Nevertheless, three lines of evidence favored a predominant association of ligand with dendrites of intrinsic striatal neurons: (1) the high frequency with which labeled interfaces implicated a dendrite, (2) the enrichment of dendrodendriticmore » interfaces, and (3) the occurrence of dendritic profiles labeled at several contact points along their plasma membranes. A small proportion of labeled sites was associated with axo-axonic interfaces, which may subserve the {kappa} opioid-induced regulation of presynaptic dopamine and acetylcholine release documented in guinea pig neostriatum. These results support the hypothesis that in mammalian brain {kappa} opioid receptors are conformationally and functionally distinct from {mu} and {delta} types.« less

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.

Phylogenetic Distribution of Leaf Spectra and Optically Derived Functional Traits in the American Oaks

NASA Astrophysics Data System (ADS)

Cavender-Bares, J.; Meireles, J. E.; Couture, J. J.; Kaproth, M.; Townsend, P. A.

2015-12-01

Detecting functional traits of species, genotypes and phylogenetic lineages is critical in monitoring functional biodiversity remotely. We examined the phylogenetic distribution of leaf spectra across the American Oaks for 35 species under greenhouse conditions as well as genetic variation in leaf spectra across Central American populations of a single species grown in common gardens in Honduras. We found significant phylogenetic signal in the leaf spectra (Blomberg's K > 1.0), indicating similarity in spectra among close relatives. Across species, full range leaf spectra were used in a Partial Least Squares Discriminant Analysis (PLS-DA) that allowed species calibration (kappa statistic = 0.55). Validation of the model used to detect species (kappa statistic = 0.4) indicated reasonably good detection of individual species within the same the genus. Among four populations from Belize, Costa Rica, Honduras, and Mexico within a single species (Quercus oleoides), leaf spectra were also able to differentiate populations. Ordination of population-level data using dissimilarities of predicted foliar traits, including leaf mass per area (LMA), lignin content, fiber content, chlorophyll a+b, and C:N ratio in genotypes in either watered or unwatered conditions showed significant differentiation among populations and treatments. These results provide promise for remote detection and differentiation of plant functional traits among plant phylogenetic lineages and genotypes, even among closely related populations and species.

The influence of non-Gaussian distribution functions on the time-dependent perpendicular transport of energetic particles

NASA Astrophysics Data System (ADS)

Lasuik, J.; Shalchi, A.

2018-06-01

In the current paper we explore the influence of the assumed particle statistics on the transport of energetic particles across a mean magnetic field. In previous work the assumption of a Gaussian distribution function was standard, although there have been known cases for which the transport is non-Gaussian. In the present work we combine a kappa distribution with the ordinary differential equation provided by the so-called unified non-linear transport theory. We then compute running perpendicular diffusion coefficients for different values of κ and turbulence configurations. We show that changing the parameter κ slightly increases or decreases the perpendicular diffusion coefficient depending on the considered turbulence configuration. Since these changes are small, we conclude that the assumed statistics is less significant in particle transport theory. The results obtained in the current paper support to use a Gaussian distribution function as usually done in particle transport theory.

Reactivity of the Ni-->B dative sigma-bond in the nickel boratrane compounds [kappa4-B(mimBut)3]NiX (X=Cl, OAc, NCS, N3): synthesis of a series of B-functionalized tris(2-mercapto-1-tert-butylimidazolyl)borato complexes, [YTmBut)]NiZ.

PubMed

Pang, Keliang; Tanski, Joseph M; Parkin, Gerard

2008-02-28

The nickel boratrane complexes [kappa4-B(mimBut))3]Ni(kappa1-OAc), [kappa4-B(mimBut)3]NiNCS and [kappa4-B(mimBut)3]NiN3 are obtained via metathesis of the chloride ligand of [kappa4-B(mimBut)3]NiCl with TlOAc, KSCN and NaN3, respectively; the Ni-->B bond in these complexes is a site of reactivity, thereby providing a means of synthesizing nickel complexes that feature B-functionalized tris(mercaptoimidazolyl)borate derivatives, [YTmBut]NiZ.

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…

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.

Diameter Effect Curve and Detonation Front Curvature Measurements for ANFO

NASA Astrophysics Data System (ADS)

Catanach, R. A.; Hill, L. G.

2002-07-01

Diameter effect and front curvature measurements are reported for rate stick experiments on commercially available prilled ANFO (ammonium-nitrate/fuel-oil) at ambient temperature. The shots were fired in paper tubes so as to provide minimal confinement. Diameters ranged from 77 mm (approximately failure diameter) to 205 mm, with the tube length being ten diameters in all cases. Each detonation wave shape was fit with an analytic form, from which the local normal velocity Dn, and local total curvature kappa, were generated as a function of radius R, then plotted parametrically to generate a Dn(kappa) function. The observed behavior deviates substantially from that of previous explosives, for which curves for different diameters overlay well for small kappa but diverge for large kappa, and for which kappa increases monotonically with R. For ANFO, we find that Dn(kappa) curves for individual sticks 1) show little or no overlap--with smaller sticks lying to the right of larger ones, 2) exhibit a large velocity deficit with little kappa variation, and 3) reach a peak kappa at an intermediate R.

Biased immunoglobulin light chain gene usage in the shark1

PubMed Central

Iacoangeli, Anna; Lui, Anita; Naik, Ushma; Ohta, Yuko; Flajnik, Martin; Hsu, Ellen

2015-01-01

This study of a large family of kappa light (L) chain clusters in nurse shark completes the characterization of its classical immunoglobulin (Ig) gene content (two heavy chain classes, mu and omega, and four L chain isotopes, kappa, lambda, sigma, and sigma-2). The shark kappa clusters are minigenes consisting of a simple VL-JL-CL array, where V to J recombination occurs over a ~500 bp interval, and functional clusters are widely separated by at least 100 kb. Six out of ca. 39 kappa clusters are pre-rearranged in the germline (GL-joined). Unlike the complex gene organization and multistep assembly process of Ig in mammals, each shark Ig rearrangement, somatic or in the germline, appears to be an independent event localized to the minigene. This study examined the expression of functional, non-productive, and sterile transcripts of the kappa clusters compared to the other three L chain isotypes. Kappa cluster usage was investigated in young sharks, and a skewed pattern of split gene expression was observed, one similar in functional and non-productive rearrangements. These results show that the individual activation of the spatially distant kappa clusters is non-random. Although both split and GL-joined kappa genes are expressed, the latter are prominent in young animals and wane with age. We speculate that, in the shark, the differential activation of the multiple isotypes can be advantageously used in receptor editing. PMID:26342033

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

Zukin, R.S.; Eghbali, M.; Olive, D.

{kappa} opioid receptors ({kappa} receptors) have been characterized in homogenates of guinea pig and rat brain under in vitro binding conditions. {kappa} receptors were labeled by using the tritiated prototypic {kappa} opioid ethylketocyclazocine under conditions in which {mu} and {delta} opioid binding was suppressed. In the case of guinea pig brain membranes, a single population of high-affinity {kappa} opioid receptor sites was observed. In contrast, in the case of rat brain, two populations of {kappa} sites were observed. To test the hypothesis that the high- and low-affinity {kappa} sites represent two distinct {kappa} receptor subtypes, a series of opioids weremore » tested for their abilities to compete for binding to the two sites. U-69,593 and Cambridge 20 selectively displaced the high-affinity {kappa} site in both guinea pig and rat tissue, but were inactive at the rat-brain low-affinity site. Other {kappa} opioid drugs competed for binding to both sites, but with different rank orders of potency. Quantitative light microscopy in vitro autoradiography was used to visualize the neuroanatomical pattern of {kappa} receptors in rat and guinea pig brain. The distribution patterns of the two {kappa} receptor subtypes of rat brain were clearly different. Collectively, these data provide direct evidence for the presence of two {kappa} receptor subtypes; the U-69,593-sensitive, high-affinity {kappa}{sub 1} site predominates in guinea pig brain, and the U-69,593-insensitive, low-affinity {kappa}{sub 2} site predominates in rat brain.« less

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.

Comparison of the King’s and MiToS staging systems for ALS

PubMed Central

Fang, Ton; Al Khleifat, Ahmad; Stahl, Daniel R; Lazo La Torre, Claudia; Murphy, Caroline; Young, Carolyn; Shaw, Pamela J; Leigh, P Nigel; Al-Chalabi, Ammar

2017-01-01

Abstract Objective: To investigate and compare two ALS staging systems, King’s clinical staging and Milano-Torino (MiToS) functional staging, using data from the LiCALS phase III clinical trial (EudraCT 2008-006891-31). Methods: Disease stage was derived retrospectively for each system from the ALS Functional Rating Scale-Revised subscores using standard methods. The two staging methods were then compared for timing of stages using box plots, correspondence using chi-square tests, agreement using a linearly weighted kappa coefficient and concordance using Spearman’s rank correlation. Results: For both systems, progressively higher stages occurred at progressively later proportions of the disease course, but the distribution differed between the two methods. King’s stage 3 corresponded to MiToS stage 1 most frequently, with earlier King’s stages 1 and 2 largely corresponding to MiToS stage 0 or 1. The Spearman correlation was 0.54. There was fair agreement between the two systems with kappa coefficient of 0.21. Conclusion: The distribution of timings shows that the two systems are complementary, with King’s staging showing greatest resolution in early to mid-disease corresponding to clinical or disease burden, and MiToS staging having higher resolution for late disease, corresponding to functional involvement. We therefore propose using both staging systems when describing ALS. PMID:28054828

A novel form of the RelA nuclear factor kappaB subunit is induced by and forms a complex with the proto-oncogene c-Myc.

PubMed Central

Chapman, Neil R; Webster, Gill A; Gillespie, Peter J; Wilson, Brian J; Crouch, Dorothy H; Perkins, Neil D

2002-01-01

Members of both Myc and nuclear factor kappaB (NF-kappaB) families of transcription factors are found overexpressed or inappropriately activated in many forms of human cancer. Furthermore, NF-kappaB can induce c-Myc gene expression, suggesting that the activities of these factors are functionally linked. We have discovered that both c-Myc and v-Myc can induce a previously undescribed, truncated form of the RelA(p65) NF-kappaB subunit, RelA(p37). RelA(p37) encodes the N-terminal DNA binding and dimerization domain of RelA(p65) and would be expected to function as a trans-dominant negative inhibitor of NF-kappaB. Surprisingly, we found that RelA(p37) no longer binds to kappaB elements. This result is explained, however, by the observation that RelA(p37), but not RelA(p65), forms a high-molecular-mass complex with c-Myc. These results demonstrate a previously unknown functional and physical interaction between RelA and c-Myc with many significant implications for our understanding of the role that both proteins play in the molecular events underlying tumourigenesis. PMID:12027803

Genetics Home Reference: anhidrotic ectodermal dysplasia with immune deficiency

MedlinePlus

... The proteins produced from these two genes regulate nuclear factor-kappa-B. Nuclear factor-kappa-B is a group of related ... proteins with impaired function, which reduces activation of nuclear factor-kappa-B. These changes disrupt certain signaling ...

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

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.

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…

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.

Scale covariant gravitation. V - Kinetic theory. VI - Stellar structure and evolution

NASA Technical Reports Server (NTRS)

Hsieh, S.-H.; Canuto, V. M.

1981-01-01

A scale covariant kinetic theory for particles and photons is developed. The mathematical framework of the theory is given by the tangent bundle of a Weyl manifold. The Liouville equation is derived, and solutions to corresponding equilibrium distributions are presented and shown to yield thermodynamic results identical to the ones obtained previously. The scale covariant theory is then used to derive results of interest to stellar structure and evolution. A radiative transfer equation is derived that can be used to study stellar evolution with a variable gravitational constant. In addition, it is shown that the sun's absolute luminosity scales as L approximately equal to GM/kappa, where kappa is the stellar opacity. Finally, a formula is derived for the age of globular clusters as a function of the gravitational constant using a previously derived expression for the absolute luminosity.

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.

Non-Maxwellian effects in magnetosonic solitons

NASA Astrophysics Data System (ADS)

Pokhotelov, O. A.; Balikhin, M. A.; Onishchenko, O. G.; Walker, S. N.

2007-12-01

The role of non-Maxwellian effects on magnetosonic (MS) solitons propagating perpendicular to the external magnetic field in high- β plasmas is analysed. It is shown that they can exist in the form of either humps or holes in the magnetic field in which the field is either increased or decreased relative to the background magnetic field. The shape of the solitary structure depends upon both the form of the ion velocity distribution function and the wave dispersion. A nonlinear equation describing the propagation of MS solitons in high- β plasmas with an arbitrary particle velocity distribution function is derived. It is shown that for Maxwellian and bi-Maxwellian plasmas MS solitons can only exist in the form of the magnetic humps. The same is true for plasmas possessing either a kappa distribution or Kennel-Ashour-Abdalla equilibria. However, plasmas with a ring type ion velocity distribution or a Dory-Guest-Harris distribution with large loss-cone index can support the formation of magnetic holes. The theoretical results obtained are then compared with recent satellite observations.

Equatorial distributions of energetic ion moments in Saturn's magnetosphere using Cassini/MIMI measurements

NASA Astrophysics Data System (ADS)

Dialynas, K.; Roussos, E.; Regoli, L.; Paranicas, C.; Krimigis, S. M.; Kane, M.; Mitchell, D. G.; Hamilton, D. C.

2016-12-01

We use kappa distribution fits to combined Charge Energy Mass Spectrometer (CHEMS, 3 to 236 keV/e), Low Energy Magnetosphere Measurements System (LEMMS, 0.024 < E < 18 MeV), and Ion Neutral Camera (INCA, 5.2 to >220 keV for H+) proton and singly ionized energetic ion spectra to calculate the >20 keV energetic ion moments inside Saturn's magnetosphere. Using a realistic magnetic field model (Khurana et al. 2007) and data from the entire Cassini mission to date (2004-2016), we map the ion measurements to the equatorial plane and via the modeled kappa distribution spectra we produce the equatorial distributions of all ion integral moments, focusing on partial density, integral intensity, partial pressure, integral energy intensity; as well as the characteristic energy (EC=IE/In), Temperature and κ-index of these ions as a function of Local Time (00:00 to 24:00 hrs) and L-Shell (5-20). A modified version of the semi-empirical Roelof and Skinner [2000] model is then utilized to retrieve the equatorial H+ and O+ pressure, density and temperature in Saturn's magnetosphere in both local time and L-shell. We find that a) although the H+ and O+ partial pressures and densities are nearly comparable, the >20 keV protons have higher number and energy intensities at all radial distances (L>5) and local times; b) the 12

On the effects of suprathermal populations in dusty plasmas: The case of dust-ion-acoustic waves

NASA Astrophysics Data System (ADS)

Lazar, M.; Kourakis, I.; Poedts, S.; Fichtner, H.

2018-07-01

Suprathermal populations with energetic distributions deviating from a standard Maxwellian are ubiquitous in dusty plasmas from space environments, as a proof that these systems are out of thermal equilibrium. The excess of free energy may have important implications in the relaxation processes by the plasma waves and fluctuations, as well as in their dissipation. In order to emphasize the effects of suprathermal populations a new realistic interpretation is proposed on the basis of an advanced Kappa modeling in accord with the observations. This article is focused on the kinetic description of dust-modified ion acoustic (DIA) waves in the presence of Kappa-distributed (suprathermal) particles. Our methodology follows closely recent considerations on the structural characteristics of Kappa distributions, contrasting the high-energy tails enhanced by the suprathermal populations with the Maxwellian (thermal) core of the distribution. The effects on DIA waves are found to be highly dependent on the nature of suprathermal particles: both the wave-frequency and Landau damping rate are inhibited by the suprathermal electrons, while the suprathermal ions have an opposite influence.

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.

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.

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

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.

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.

The TRIF-dependent signaling pathway is not required for acute cerebral ischemia/reperfusion injury in mice

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

Hua, Fang, E-mail: fhua2@emory.edu; Wang, Jun; Sayeed, Iqbal

TIR domain-containing adaptor protein (TRIF) is an adaptor protein in Toll-like receptor (TLR) signaling pathways. Activation of TRIF leads to the activation of interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-{kappa}B). While studies have shown that TLRs are implicated in cerebral ischemia/reperfusion (I/R) injury and in neuroprotection against ischemia afforded by preconditioning, little is known about TRIF's role in the pathological process following cerebral I/R. The present study investigated the role that TRIF may play in acute cerebral I/R injury. In a mouse model of cerebral I/R induced by transient middle cerebral artery occlusion, we examined themore » activation of NF-{kappa}B and IRF3 signaling in ischemic cerebral tissue using ELISA and Western blots. Neurological function and cerebral infarct size were also evaluated 24 h after cerebral I/R. NF-{kappa}B activity and phosphorylation of the inhibitor of kappa B (I{kappa}B{alpha}) increased in ischemic brains, but IRF3, inhibitor of {kappa}B kinase complex-{epsilon} (IKK{epsilon}), and TANK-binding kinase1 (TBK1) were not activated after cerebral I/R in wild-type (WT) mice. Interestingly, TRIF deficit did not inhibit NF-{kappa}B activity or p-I{kappa}B{alpha} induced by cerebral I/R. Moreover, although cerebral I/R induced neurological and functional impairments and brain infarction in WT mice, the deficits were not improved and brain infarct size was not reduced in TRIF knockout mice compared to WT mice. Our results demonstrate that the TRIF-dependent signaling pathway is not required for the activation of NF-{kappa}B signaling and brain injury after acute cerebral I/R.« less

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 thrombo-inflammatory disorders.« less

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.

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.

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.

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.

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.

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.

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

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.

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

A Comparison of Four Indices for Combining Distance and Dose Differences

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

Thomas, Simon J., E-mail: simon.thomas@addenbrookes.nhs.uk; Cowley, Ian R.

2012-04-01

Purpose: When one is comparing two dose distributions, a number of methods have been published to combine dose difference and distance to agreement into a single measure. Some have been defined as pass/fail indices and some as numeric indices. We show that the pass/fail indices can all be used to derive numeric indices, and we compare the results of using these indices to evaluate one-dimensional (1D) and three-dimensional (3D) dose distributions, with the aim of selecting the most appropriate index for use in different circumstances. Methods and Materials: The indices compared are the gamma index, the kappa index, the indexmore » in International Commission on Radiation Units and Measurements Report 83, and a box index. Comparisons are made for 1D and 3D distributions. The 1D distribution is chosen to have a variety of dose gradients. The 3D distribution is taken from a clinical treatment plan. The effect of offsetting distributions by known distances and doses is studied. Results: The International Commission on Radiation Units and Measurements Report 83 index causes large discontinuities unless the dose gradient cutoff is set to equal the ratio of the dose tolerance to the distance tolerance. If it is so set, it returns identical results to the kappa index. Where the gradient is very high or very low, all the indices studied in this article give similar results for the same tolerance values. For moderate gradients, they differ, with the box index being the least strict, followed by the gamma index, and with the kappa index being the most strict. Conclusions: If the clinical tolerances are much greater than the uncertainties of the measuring system, the kappa index should be used, with tolerance values determined by the clinical tolerances. In cases where the uncertainties of the measuring system dominate, the box index will be best able to determine errors in the delivery system.« less

Comparative evaluation of Plateletworks, Multiplate analyzer and Platelet function analyzer-200 in cardiology patients.

PubMed

Kim, Jeeyong; Cho, Chi Hyun; Jung, Bo Kyeung; Nam, Jeonghun; Seo, Hong Seog; Shin, Sehyun; Lim, Chae Seung

2018-04-14

The objective of this study was to comparatively evaluate three commercial whole-blood platelet function analyzer systems: Platelet Function Analyzer-200 (PFA; Siemens Canada, Mississauga, Ontario, Canada), Multiplate analyzer (MP; Roche Diagnostics International Ltd., Rotkreuz, Switzerland), and Plateletworks Combo-25 kit (PLW; Helena Laboratories, Beaumont, TX, USA). Venipuncture was performed on 160 patients who visited a department of cardiology. Pairwise agreement among the three platelet function assays was assessed using Cohen's kappa coefficient and percent agreement within the reference limit. Kappa values with the same agonists were poor between PFA-collagen (COL; agonist)/adenosine diphosphate (ADP) and MP-ADP (-0.147), PFA-COL/ADP and PLW-ADP (0.089), MP-ADP and PLW-ADP (0.039), PFA-COL/ADP and MP-COL (-0.039), and between PFA-COL/ADP and PLW-COL (-0.067). Nonetheless, kappa values for the same assay principle with a different agonist were slightly higher between PFA-COL/ADP and PFA-COL/EPI (0.352), MP-ADP and MP-COL (0.235), and between PLW-ADP and PLW-COL (0.247). The range of percent agreement values was 38.7% to 73.8%. Therefore, various measurements of platelet function by more than one method were needed to obtain a reliable interpretation of platelet function considering low kappa coefficient and modest percent agreement rates among 3 different platelet function tests.

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.

Direct Determination of the Dependence of the Surface Shear and Dilatational Viscosities on the Thermodynamic State of the Interface: Theoretical Foundations.

PubMed

Lopez; Hirsa

1998-10-01

Recent developments in nonlinear optical techniques for noninvasive probing of a surfactant influenced gas/liquid interface allow for the measurement of the surfactant surface concentration, c, and thus provide new opportunities for the direct determination of its intrinsic viscosities. Here, we present the theoretical foundations, based on the Boussinesq-Scriven surface model without the usual simplification of constant viscosities, for an experimental technique to directly measure the surface shear (µs) and dilatational (kappas) viscosities of a Newtonian interface as functions of the surfactant surface concentration. This ability to directly measure the surfactant concentration permits the use of a simple surface flow for the measurement of the surface viscosities. The requirements are that the interface must be nearly flat, and the flow steady, axisymmetric, and swirling; these flow conditions can be achieved in the deep-channel viscometer driven at relatively fast rates. The tangential stress balance on such an interface leads to two equations; the balance in the azimuthal direction involves only µs and its gradients, and the balance in the radial direction involves both µs and kappas and their gradients. By further exploiting recent developments in laser-based flow measuring techniques, the surface velocities and their gradients which appear in the two equations can be measured directly. The surface tension gradient, which appears in the radial balance equation, is incorporated from the equation of state for the surfactant system and direct measurements of the surfactant surface concentration distribution. The stress balance equations are then ordinary differential equations in the surface viscosities as functions of radial position, which can be readily integrated. Since c is measured as a function of radial position, we then have a direct measurement of µs and kappas as functions of c. Numerical computations of the Navier-Stokes equations are performed to determine the appropriate conditions to achieve the requisite secondary flow. Copyright 1998 Academic Press.

Flavocoxid counteracts muscle necrosis and improves functional properties in mdx mice: a comparison study with methylprednisolone.

PubMed

Messina, Sonia; Bitto, Alessandra; Aguennouz, M'hammed; Mazzeo, Anna; Migliorato, Alba; Polito, Francesca; Irrera, Natasha; Altavilla, Domenica; Vita, Gian Luca; Russo, Massimo; Naro, Antonino; De Pasquale, Maria Grazia; Rizzuto, Emanuele; Musarò, Antonio; Squadrito, Francesco; Vita, Giuseppe

2009-12-01

Muscle degeneration in dystrophic muscle is exacerbated by the endogenous inflammatory response and increased oxidative stress. A key role is played by nuclear factor(NF)-kappaB. We showed that NF-kappaB inhibition through compounds with also antioxidant properties has beneficial effects in mdx mice, the murine model of Duchenne muscular dystrophy (DMD), but these drugs are not available for clinical studies. We evaluated whether flavocoxid, a mixed flavonoid extract with anti-inflammatory, antioxidant and NF-kappaB inhibiting properties, has beneficial effects in mdx mice in comparison with methylprednisolone, the gold standard treatment for DMD patients. Five-week-old mdx mice were treated for 5 weeks with flavocoxid, methylprednisolone or vehicle. The evaluation of in vivo and ex vivo functional properties and morphological parameters was performed. Serum samples were assayed for oxidative stress markers, creatine-kinase (CK) and leukotriene B-4. Cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), tumor necrosis factor-alpha, p-38, JNK1 expression was evaluated in muscle by western blot analysis. NF-kappaB binding activity was investigated by electrophoresis mobility shift assay. The administration of flavocoxid: (1) ameliorated functional properties in vivo and ex vivo; (2) reduced CK; (3) reduced the expression of oxidative stress markers and of inflammatory mediators; (4) inhibited NF-kappaB and mitogen-activated protein kinases (MAPKs) signal pathways; (5) reduced muscle necrosis and enhanced regeneration. Our results highlight the detrimental effects of oxidative stress and NF-kappaB, MAPKs and COX/5-LOX pathways in the dystrophic process and show that flavocoxid is more effective in mdx mice than methylprednisolone.

Gaussian curvature elasticity determined from global shape transformations and local stress distributions: a comparative study using the MARTINI model.

PubMed

Hu, Mingyang; de Jong, Djurre H; Marrink, Siewert J; Deserno, Markus

2013-01-01

We calculate the Gaussian curvature modulus kappa of a systematically coarse-grained (CG) one-component lipid membrane by applying the method recently proposed by Hu et al. [Biophys. J., 2012, 102, 1403] to the MARTINI representation of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). We find the value kappa/kappa = -1.04 +/- 0.03 for the elastic ratio between the Gaussian and the mean curvature modulus and deduce kappa(m)/kappa(m) = -0.98 +/- 0.09 for the monolayer elastic ratio, where the latter is based on plausible assumptions for the distance z0 of the monolayer neutral surface from the bilayer midplane and the spontaneous lipid curvature K(0m). By also analyzing the lateral stress profile sigma0(z) of our system, two other lipid types and pertinent data from the literature, we show that determining K(0m) and kappa through the first and second moment of sigma0(z) gives rise to physically implausible values for these observables. This discrepancy, which we previously observed for a much simpler CG model, suggests that the moment conditions derived from simple continuum assumptions miss the effect of physically important correlations in the lipid bilayer.

Opioid-receptor subtype agonist-induced enhancements of sucrose intake are dependent upon sucrose concentration.

PubMed

Ruegg, H; Yu, W Z; Bodnar, R J

1997-07-01

Selective mu ([D-Ala2, N-Me-Phe4, Gly-ol5]-enkephalin (DAMGO)), delta1 ([D-Pen2, D-Pen5]-enkephalin (DPDPE)), delta2 ([D-Ala2, Glu4]-Deltorphin (Delt II)), kappa1 (U50488H) and kappa3 (naloxone benzoylhydrazone (NalBzOH)) opioid agonists each stimulate food intake in rats. Whereas studies with selective opioid antagonists implicate mu and kappa1 receptors in the mediation of sucrose intake, studies with selective opioid agonists implicate mu and delta receptors in the mediation of saccharin intake. The present study determined if specific delta1, delta2, kappa1, kappa3 and mu opioid-receptor subtype agonists produced similar alterations in sucrose intake as a function of sucrose concentration (0.5%, 2.5%, 10%) across a 1-h time-course. Each of these agonists significantly increased sucrose intake with variations in pattern, magnitude, and consistency as a function of sucrose concentration. Whereas the mu opioid agonist, DAMGO, and the delta1 opioid agonist, DPDPE, each enhanced sucrose intake at higher (2.5%, 10%), but not lower (0.5%), concentrations, the delta2 opioid agonist, Delt II, increased sucrose intake at lower (0.5%, 2.5%), but not higher (10%), concentrations. Kappa opioid agonists produced less consistent effects. The kappa1 opioid agonist, U50488H, increased sucrose intake at high (10%) concentrations and decreased sucrose intake at low (0.5%) concentrations, and the kappa3 opioid agonist, NalBzOH, inconsistently increased sucrose intake at the 0.5% (20 microg) and 10% (1 microg) concentrations. Thus, these data further implicate mu, delta1, and delta2 opioid mediation of palatable intake, particularly of its orosensory characteristics.

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.

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

Analysis of Morphological Features of Benign and Malignant Breast Cell Extracted From FNAC Microscopic Image Using the Pearsonian System of Curves.

PubMed

Rajbongshi, Nijara; Bora, Kangkana; Nath, Dilip C; Das, Anup K; Mahanta, Lipi B

2018-01-01

Cytological changes in terms of shape and size of nuclei are some of the common morphometric features to study breast cancer, which can be observed by careful screening of fine needle aspiration cytology (FNAC) images. This study attempts to categorize a collection of FNAC microscopic images into benign and malignant classes based on family of probability distribution using some morphometric features of cell nuclei. For this study, features namely area, perimeter, eccentricity, compactness, and circularity of cell nuclei were extracted from FNAC images of both benign and malignant samples using an image processing technique. All experiments were performed on a generated FNAC image database containing 564 malignant (cancerous) and 693 benign (noncancerous) cell level images. The five-set extracted features were reduced to three-set (area, perimeter, and circularity) based on the mean statistic. Finally, the data were fitted to the generalized Pearsonian system of frequency curve, so that the resulting distribution can be used as a statistical model. Pearsonian system is a family of distributions where kappa (κ) is the selection criteria computed as functions of the first four central moments. For the benign group, kappa (κ) corresponding to area, perimeter, and circularity was -0.00004, 0.0000, and 0.04155 and for malignant group it was 1016942, 0.01464, and -0.3213, respectively. Thus, the family of distribution related to these features for the benign and malignant group were different, and therefore, characterization of their probability curve will also be different.

Inhibition of GSK3 differentially modulates NF-{kappa}B, CREB, AP-1 and {beta}-catenin signaling in hepatocytes, but fails to promote TNF-{alpha}-induced apoptosis

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

Goetschel, Frank; Kern, Claudia; Lang, Simona

2008-04-01

Glycogen synthase kinase-3 (GSK-3) is known to modulate cell survival and apoptosis through multiple intracellular signaling pathways. However, its hepatoprotective function and its role in activation of NF-{kappa}B and anti-apoptotic factors are poorly understood and remain controversial. Here we investigated whether inhibition of GSK-3 could induce apoptosis in the presence of TNF-{alpha} in primary mouse hepatocytes. We show that pharmacological inhibition of GSK-3 in primary mouse hepatocytes does not lead to TNF-{alpha}-induced apoptosis despite reduced NF-{kappa}B activity. Enhanced stability of I{kappa}B-{alpha} appears to be responsible for lower levels of nuclear NF-{kappa}B and hence reduced transactivation. Additionally, inhibition of GSK-3 wasmore » accompanied by marked upregulation of {beta}-catenin, AP-1, and CREB transcription factors. Stimulation of canonical Wnt signaling and CREB activity led to elevated levels of anti-apoptotic factors. Hence, survival of primary mouse hepatocytes may be caused by the activation and/or upregulation of other key regulators of liver homeostasis and regeneration. These signaling molecules may compensate for the compromised anti-apoptotic function of NF-{kappa}B and allow survival of hepatocytes in the presence of TNF-{alpha} and GSK-3 inhibition.« less

Neutron Capture Energies for Flux Normalization and Approximate Model for Gamma-Smeared Power

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

Kim, Kang Seog; Clarno, Kevin T.; Liu, Yuxuan

The Consortium for Advanced Simulation of Light Water Reactors (CASL) Virtual Environment for Reactor Applications (VERA) neutronics simulator MPACT has used a single recoverable fission energy for each fissionable nuclide assuming that all recoverable energies come only from fission reaction, for which capture energy is merged with fission energy. This approach includes approximations and requires improvement by separating capture energy from the merged effective recoverable energy. This report documents the procedure to generate recoverable neutron capture energies and the development of a program called CapKappa to generate capture energies. Recoverable neutron capture energies have been generated by using CapKappa withmore » the evaluated nuclear data file (ENDF)/B-7.0 and 7.1 cross section and decay libraries. The new capture kappas were compared to the current SCALE-6.2 and the CASMO-5 capture kappas. These new capture kappas have been incorporated into the Simplified AMPX 51- and 252-group libraries, and they can be used for the AMPX multigroup (MG) libraries and the SCALE code package. The CASL VERA neutronics simulator MPACT does not include a gamma transport capability, which limits it to explicitly estimating local energy deposition from fission, neutron, and gamma slowing down and capture. Since the mean free path of gamma rays is typically much longer than that for the neutron, and the total gamma energy is about 10% to the total energy, the gamma-smeared power distribution is different from the fission power distribution. Explicit local energy deposition through neutron and gamma transport calculation is significantly important in multi-physics whole core simulation with thermal-hydraulic feedback. Therefore, the gamma transport capability should be incorporated into the CASL neutronics simulator MPACT. However, this task will be timeconsuming in developing the neutron induced gamma production and gamma cross section libraries. This study is to investigate an approximate model to estimate gammasmeared power distribution without performing any gamma transport calculation. A simple approximate gamma smearing model has been investigated based on the facts that pinwise gamma energy depositions are almost flat over a fuel assembly, and assembly-wise gamma energy deposition is proportional to kappa-fission energy deposition. The approximate gamma smearing model works well for single assembly cases, and can partly improve the gamma smeared power distribution for the whole core model. Although the power distributions can be improved by the approximate gamma smearing model, still there is an issue to explicitly obtain local energy deposition. A new simple approach or gamma transport/diffusion capability may need to be incorporated into MPACT to estimate local energy deposition for more robust multi-physics simulation.« less

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 TNF{alpha}-induced NF-{kappa}B activity. Therefore, we conclude that NF-{kappa}B signalling in astrocytes is not a major target for flavonoids.« less

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.

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.

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.

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 enhanced the IR-induced inhibition of cell survival. Conclusions: These results strongly suggest that curcumin inhibits IR-induced TA in an NF{kappa}B dependent manner in human neuroblastoma cells.« less

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.

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.

Metastatic function of BMP-2 in gastric cancer cells: The role of PI3K/AKT, MAPK, the NF-{kappa}B pathway, and MMP-9 expression

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

Kang, Myoung Hee; Oh, Sang Cheul; Lee, Hyun Joo

2011-07-15

Bone morphogenetic proteins (BMPs) have been implicated in tumorigenesis and metastatic progression in various types of cancer cells, but the role and cellular mechanism in the invasive phenotype of gastric cancer cells is not known. Herein, we determined the roles of phosphoinositide 3-kinase (PI3K)/AKT, extracellular signal-regulated protein kinase (ERK), nuclear factor (NF)-{kappa}B, and matrix metalloproteinase (MMP) expression in BMP-2-mediated metastatic function in gastric cancer. We found that stimulation of BMP-2 in gastric cancer cells enhanced the phosphorylation of AKT and ERK. Accompanying activation of AKT and ERK kinase, BMP-2 also enhanced phosphorylation/degradation of I{kappa}B{alpha} and the nuclear translocation/activation of NF-{kappa}B.more » Interestingly, blockade of PI3K/AKT and ERK signaling using LY294002 and PD98059, respectively, significantly inhibited BMP-2-induced motility and invasiveness in association with the activation of NF-{kappa}B. Furthermore, BMP-2-induced MMP-9 expression and enzymatic activity was also significantly blocked by treatment with PI3K/AKT, ERK, or NF-{kappa}B inhibitors. Immunohistochemistry staining of 178 gastric tumor biopsies indicated that expression of BMP-2 and MMP-9 had a significant positive correlation with lymph node metastasis and a poor prognosis. These results indicate that the BMP-2 signaling pathway enhances tumor metastasis in gastric cancer by sequential activation of the PI3K/AKT or MAPK pathway followed by the induction of NF-{kappa}B and MMP-9 activity, indicating that BMP-2 has the potential to be a therapeutic molecular target to decrease metastasis.« less

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

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.

Comparison of an expert system with other clinical scores for the evaluation of severity of asthma.

PubMed

Gautier, V; Rédier, H; Pujol, J L; Bousquet, J; Proudhon, H; Michel, C; Daurès, J P; Michel, F B; Godard, P

1996-01-01

"Asthmaexpert" was produced at the special request of several clinicians in order to obtain a better understanding of the medical decisions taken by clinical experts in the management of asthmatic patients. In order to assess the severity of asthma, a new score called Artificial Intelligence score (AI score), produced by Asthmaexpert, was compared with three other scores (Aas, Hargreave and Brooks). One hundred patients were enrolled prospectively in the study during their first consultation in the out-patient clinic. Distribution of severity level according to the different scores was studied, and the reliability between AI and other scores was evaluated by Kappa and MacNemar tests. Correlations with functional parameters were performed. The AI score assessed higher levels of severity than the other scores (Kappa = 18, 28 and 10% for Aas, Hargreave and Brooks, respectively) with significant MacNemar test in all cases. There was a significant correlation between AI score and forced expiratory volume in one second (FEV1) (r = 0.73). These data indicate that the AI score is a severity score which defines higher levels of severity than the chosen scores. Correlations for functional parameters are good. This score appears easy to use for the first consultation of an asthmatic patient.

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

In vitro safety evaluation of human nasal epithelial cell monolayers exposed to carrageenan sinus wash.

PubMed

Ramezanpour, Mahnaz; Murphy, Jae; Smith, Jason L P; Vreugde, Sarah; Psaltis, Alkis James

2017-12-01

Carrageenans have shown to reduce the viral load in nasal secretions and lower the incidence of secondary infections in children with common cold. Despite the widespread use of carrageenans in topical applications, the effect of carrageenans on the sinonasal epithelial barrier has not been elucidated. We investigate the effect of different carrageenans on the sinonasal epithelial barrier and inflammatory response in vitro. Iota and Kappa carrageenan delivered in saline irrigation solutions applied to air-liquid interface (ALI) cultures of primary human nasal epithelial cells from chronic rhinosinusitis patients and controls. Epithelial barrier structure was assessed by measuring the transepithelial electrical resistance (TEER) and immunolocalization of F actin. Ciliary beat frequency (CBF), toxicity, and inflammatory response was studied. Kappa or Iota carrageenan in the different solutions was not toxic, did not have detrimental effects on epithelial barrier structure and CBF. Rather, application of Kappa carrageenan significantly increased TEER and suppressed interleukin 6 (IL-6) secretion in ALI cultures from CRS patients. Kappa or Iota carrageenan solution was safe and did not negatively affect epithelial barrier function. Kappa carrageenan increased TEER and decreased IL-6 production in CRS patients, indicating positive effects on epithelial barrier function in vitro. © 2017 ARS-AAOA, LLC.

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.

Sodium phenylbutyrate prolongs survival and regulates expression of anti-apoptotic genes in transgenic amyotrophic lateral sclerosis mice.

PubMed

Ryu, Hoon; Smith, Karen; Camelo, Sandra I; Carreras, Isabel; Lee, Junghee; Iglesias, Antonio H; Dangond, Fernando; Cormier, Kerry A; Cudkowicz, Merit E; Brown, Robert H; Ferrante, Robert J

2005-06-01

Multiple molecular defects trigger cell death in amyotrophic lateral sclerosis (ALS). Among these, altered transcriptional activity may perturb many cellular functions, leading to a cascade of secondary pathological effects. We showed that pharmacological treatment, using the histone deacetylase inhibitor sodium phenylbutyrate, significantly extended survival and improved both the clinical and neuropathological phenotypes in G93A transgenic ALS mice. Phenylbutyrate administration ameliorated histone hypoacetylation observed in G93A mice and induced expression of nuclear factor-kappaB (NF-kappaB) p50, the phosphorylated inhibitory subunit of NF-kappaB (pIkappaB) and beta cell lymphoma 2 (bcl-2), but reduced cytochrome c and caspase expression. Curcumin, an NF-kappaB inhibitor, and mutation of the NF-kappaB responsive element in the bcl-2 promoter, blocked butyrate-induced bcl-2 promoter activity. We provide evidence that the pharmacological induction of NF-kappaB-dependent transcription and bcl-2 gene expression is neuroprotective in ALS mice by inhibiting programmed cell death. Phenylbutyrate acts to phosphorylate IkappaB, translocating NF-kappaB p50 to the nucleus, or to directly acetylate NF-kappaB p50. NF-kappaB p50 transactivates bcl-2 gene expression. Up-regulated bcl-2 blocks cytochrome c release and subsequent caspase activation, slowing motor neuron death. These transcriptional and post-translational pathways ultimately promote motor neuron survival and ameliorate disease progression in ALS mice. Phenylbutyrate may therefore provide a novel therapeutic approach for the treatment of patients with ALS.

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.

Functional characterization of bovine TIRAP and MyD88 in mediating bacterial lipopolysaccharide-induced endothelial NF-kappaB activation and apoptosis.

PubMed

Cates, Elizabeth A; Connor, Erin E; Mosser, David M; Bannerman, Douglas D

2009-11-01

Mastitis is a prevalent disease in dairy cows. Gram-negative bacteria, which express the pro-inflammatory molecule lipopolysaccharide (LPS), are responsible for the majority of acute clinical cases of mastitis. Previous studies have identified differential susceptibility of human and bovine endothelial cells (EC) to the pro-inflammatory and injury-inducing effects of LPS. The Toll-like receptor (TLR)-4 signaling pathway, which is activated by LPS, has been well studied in humans, but not in ruminants. Human myeloid differentiation-factor 88 (MyD88) and TIR-domain containing adaptor protein (TIRAP) are critical proteins in the LPS-induced NF-kappaB and apoptotic signaling pathways. To assess the role of the bovine orthologs of these proteins in bovine TLR-4 signaling, dominant-negative constructs were expressed in bovine EC, and LPS-induced NF-kappaB activation and apoptosis evaluated. The results from this study indicate that bovine MyD88 and TIRAP play functional roles in transducing LPS signaling from TLR-4 to downstream effector molecules involved in NF-kappaB activation, and that TIRAP promotes apoptotic signaling.

Attrition, occlusion, (dys)function, and intervention: a systematic review.

PubMed

van 't Spijker, Arie; Kreulen, Cees M; Creugers, Nico H J

2007-06-01

Attrition and occlusal factors and masticatory function or dysfunction are thought to be related. This study aims to systematically review the literature on this topic with the emphasis to find evidence for occlusion-based treatment protocols for attrition. Literature was searched using PubMed (1980 to 2/2006) and the Cochrane Library of Clinical Trials with the keywords 'tooth' and 'wear'. Five steps were followed. Exclusion was based on the following: (1) reviews, case-reports, studies on non-human tooth material, and studies not published in English and (2) historical or forensic studies. Included were (3) in vivo studies. Next, studies on (4) occlusal factors, function or dysfunction [temporomandibular disorders (TMD), bruxism], or intervention, and (5) attrition were included. Two investigators independently assessed the abstracts; measure of agreement was calculated using Cohen's kappa; disagreement was resolved by discussion. Full-text articles were obtained and correlation between outcomes on occlusal factors, (dys)function, treatment, and attrition were retrieved. References in the papers included in the final analysis were cross-matched with the original list of references to add references that met the inclusion criteria. The search procedure revealed 1289 references on tooth wear. The numbers of included studies after each step were (1) 345 (kappa=0.8), (2) 287 (kappa=0.87), (3) 174 (kappa=0.99), (4) 81 (kappa=0.71), and (5) 27 (kappa=0.68). Hand searches through the reference lists revealed six additional papers to be included. Analysis of the 33 included papers failed to find sound evidence for recommending a certain occlusion-based treatment protocol above another in the management of attrition. Some studies reported correlations between attrition and anterior spatial relationships. No studies were found suggesting that absent posterior support necessarily leads to increased attrition, though one study found that fewer number of teeth resulted in higher tooth wear index (on the remaining teeth). Attrition seems to be co-existent with self-reported bruxism. Reports on attrition and TMD signs and symptoms provide little understanding of the relationship between the two.

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.

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

The tax oncoprotein of human T-cell leukemia virus type 1 associates with and persistently activates IkappaB kinases containing IKKalpha and IKKbeta.

PubMed

Chu, Z L; DiDonato, J A; Hawiger, J; Ballard, D W

1998-06-26

The Tax oncoprotein of human T-cell leukemia virus type 1 (HTLV1) chronically activates transcription factor NF-kappaB by a mechanism involving degradation of IkappaBalpha, an NF-kappaB-associated cytoplasmic inhibitor. Tax-induced breakdown of IkappaBalpha requires phosphorylation of the inhibitor at Ser-32 and Ser-36, which is also a prerequisite for the transient activation of NF-kappaB in cytokine-treated T lymphocytes. However, it remained unclear how Tax interfaces with the cellular NF-kappaB/IkappaB signaling machinery to generate a chronic rather than a transient NF-kappaB response. We now demonstrate that Tax associates with cytokine-inducible IkappaB kinase (IKK) complexes containing catalytic subunits IKKalpha and IKKbeta, which mediate phosphorylation of IkappaBalpha at Ser-32 and Ser-36. Unlike their transiently activated counterparts in cytokine-treated cells, Tax-associated forms of IKK are constitutively active in either Tax transfectants or HTLV1-infected T lymphocytes. Moreover, point mutations in Tax that ablate its IKK-binding function also prevent Tax-mediated activation of IKK and NF-kappaB. Together, these findings suggest that the persistent activation of NF-kappaB in HTLV1-infected T-cells is mediated by a direct Tax/IKK coupling mechanism.

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....

Mapping forest functional type in a forest-shrubland ecotone using SPOT imagery and predictive habitat distribution modelling

USGS Publications Warehouse

Assal, Timothy J.; Anderson, Patrick J.; Sibold, Jason

2015-01-01

The availability of land cover data at local scales is an important component in forest management and monitoring efforts. Regional land cover data seldom provide detailed information needed to support local management needs. Here we present a transferable framework to model forest cover by major plant functional type using aerial photos, multi-date Système Pour l’Observation de la Terre (SPOT) imagery, and topographic variables. We developed probability of occurrence models for deciduous broad-leaved forest and needle-leaved evergreen forest using logistic regression in the southern portion of the Wyoming Basin Ecoregion. The model outputs were combined into a synthesis map depicting deciduous and coniferous forest cover type. We evaluated the models and synthesis map using a field-validated, independent data source. Results showed strong relationships between forest cover and model variables, and the synthesis map was accurate with an overall correct classification rate of 0.87 and Cohen’s kappa value of 0.81. The results suggest our method adequately captures the functional type, size, and distribution pattern of forest cover in a spatially heterogeneous landscape.

The hepatitis B virus large surface protein (LHBs) is a transcriptional activator.

PubMed

Hildt, E; Saher, G; Bruss, V; Hofschneider, P H

1996-11-01

It has been shown that a C-terminally truncated form of the middle-sized hepatitis B virus (HBV) surface protein (MHBst) functions as a transcriptional activator. This function is dependent on the cytosolic orientation of the N-terminal PreS2 domain of MHBst, but in the case of wild-type MHBs, the PreS2 domain is contranslationally translocated into the ER lumen. Recent reports demonstrated that the PreS2 domain of the large HBV surface protein (LHBs) initially remains on the cytosolic side of the ER membrane after translation. Therefore, the question arose as to whether the LHBs protein exhibits the same transcriptional activator function as MHBst. We show that LHBs, like MHBst, is indeed able to activate a variety of promoter elements. There is evidence for a PKC-dependent activation of AP-1 and NF-kappa B by LHBs. Downstream of the PKC the functionality of c-Raf-1 kinase is a prerequisite for LHBs-dependent activation of AP-1 and NF-kappa B since inhibition of c-Raf-1 kinase abolishes LHBs-dependent transcriptional activation of AP-1 and NF-kappa B.

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.

The same IkappaBalpha mutation in two related individuals leads to completely different clinical syndromes.

PubMed

Janssen, Riny; van Wengen, Annelies; Hoeve, Marieke A; ten Dam, Monique; van der Burg, Miriam; van Dongen, Jacques; van de Vosse, Esther; van Tol, Maarten; Bredius, Robbert; Ottenhoff, Tom H; Weemaes, Corry; van Dissel, Jaap T; Lankester, Arjan

2004-09-06

Both innate and adaptive immune responses are dependent on activation of nuclear factor kappaB (NF-kappaB), induced upon binding of pathogen-associated molecular patterns to Toll-like receptors (TLRs). In murine models, defects in NF-kappaB pathway are often lethal and viable knockout mice have severe immune defects. Similarly, defects in the human NF-kappaB pathway described to date lead to severe clinical disease. Here, we describe a patient with a hyper immunoglobulin M-like immunodeficiency syndrome and ectodermal dysplasia. Monocytes did not produce interleukin 12p40 upon stimulation with various TLR stimuli and nuclear translocation of NF-kappaB was impaired. T cell receptor-mediated proliferation was also impaired. A heterozygous mutation was found at serine 32 in IkappaBalpha. Interestingly, his father has the same mutation but displays complex mosaicism. He does not display features of ectodermal dysplasia and did not suffer from serious infections with the exception of a relapsing Salmonella typhimurium infection. His monocyte function was impaired, whereas T cell function was relatively normal. Consistent with this, his T cells almost exclusively displayed the wild-type allele, whereas both alleles were present in his monocytes. We propose that the T and B cell compartment of the mosaic father arose as a result of selection of wild-type cells and that this underlies the widely different clinical phenotype.

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.

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/compulsive-like behaviors may be driven by greater kappa opioid receptor sensitivity and a hypodopaminergic state of the nucleus accumbens. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Nonlinear evolution of magnetic flux ropes. 2: Finite beta plasma

NASA Technical Reports Server (NTRS)

Osherovich, V. A.; Farrugia, C. J.; Burlaga, L. F.

1995-01-01

In this second paper on the evolution of magnetic flux ropes we study the effects of gas pressure. We assume that the energy transport is described by a polytropic relationship and reduce the set of ideal MHD equations to a single, second-order, nonlinear, ordinary differential equation for the evolution function. For this conservative system we obtain a first integral of motion. To analyze the possible motions, we use a mechanical analogue -- a one-dimensional, nonlinear oscillator. We find that the effective potential for such an oscillator depends on two parameters: the polytropic index gamma and a dimensionless quantity kappa the latter being a function of the plasma beta, the strength of the azimuthal magnetic field relative to the axial field of the flux rope, and gamma. Through a study of this effective potential we classify all possible modes of evolution of the system. In the main body of the paper, we focus on magnetic flux ropes whose field and gas pressure increase steadily towards the symmetry axis. In this case, for gamma greater than 1 and all values of kappa, only oscillations are possible. For gamma less than 1, however, both oscillations and expansion are allowed. For gamma less than 1 and kappa below a critical value, the energy of the nonlinear oscillator determines whether the flux rope will oscillate or expand to infinity. For gamma less than 1 and kappa above critical, however, only expansion occurs. Thus by increasing kappa while keeping gamma fixed (less than 1), a phase transition occurs at kappa = kappa(sub critical) and the oscillatory mode disappears. We illustrate the above theoretical considerations by the example of a flux rope of constant field line twist evolving self-similarly. For this example, we present the full numerical MHD solution. In an appendix to the paper we catalogue all possible evolutions when (1) either the magnetic field or (2) the gas pressure decreases monotonically toward the axis. We find that in these cases critical conditions can occur for gamma greater than 1. While in most cases the flux rope collapses, there are notable exceptions when, for certain ranges of kappa and gamma, collapse may be averted.

Solutal Convection Around Growing Protein Crystal and Diffusional Purification in Space

NASA Technical Reports Server (NTRS)

Lee, Chun P.; Chernov, Alexander A.

2004-01-01

At least some protein crystals were found to preferentially trap microheterogeneous impurities. The latter are, for example, dimmer molecules of the crystallizing proteines (e.g. ferritin, lysozyme), or the regular molecules on which surfaces small molecules or ions are adsorbed (e.g. acetilated lysozyme) and modi@ molecular charge. Impurities may induce lattice defects and deteriorate structural resolution. Distribution of impurities between mother solution and gorwing crystal is defined by two interrelated distribution coefficients: kappa = rho(sup c, sub 2) and K = (rho(sup c, sub 2)/rho(sup c, sub 1)/rho(sub 2)/rho(sub 1). Here, rho(sub 2), rho(sub 1) and rho(sup c, sub 2) are densities of impurity (2) and regular protein (1) in solution at the growing interface and within the crystal ("c"). For the microheterogeneous impurities studied, K approx. = 2 - 4, so that kappa approx. - 10(exp 2) - 10(exp 3), since K = kappa (rho(sub 1)/rho(sup c, sub 1) and protein solubility ratio rho(sub 1)/rho(sub=p c, sub 2) much less than 1. Therefore, a crystal growing in absence of convection purifies mother solution around itself, grows cleaner and, probably, more perfect. If convection is present, the solution flow permanently brings new impurities to the crystal. This work theoretically addressed two subjects: 1) onset of convection, 2) distribution of impurities.

Fermented guava leaf extract inhibits LPS-induced COX-2 and iNOS expression in Mouse macrophage cells by inhibition of transcription factor NF-kappaB.

PubMed

Choi, Soo-Youn; Hwang, Joon-Ho; Park, Soo-Young; Jin, Yeong-Jun; Ko, Hee-Chul; Moon, Sang-Wook; Kim, Se-Jae

2008-08-01

The goal of this study was to elucidate the antiinflammatory activities of Psidium guajava L. (guava) leaf. To improve the functionality of guava leaf, it was fermented with Phellinus linteus mycelia, Lactobacillus plantarum and Saccharomyces cerevisiae. The ethanol extract from fermented guava leaf inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production. Western blot analysis showed that fermented guava leaf extract decreased LPS-induced inducible nitric oxide synthase (iNOS) and the cyclooxygenase-2 (COX-2) protein level in RAW 264.7 cells. To investigate the mechanism involved, the study examined the effect of fermented guava leaf extract on LPS-induced nuclear factor-kappaB (NF-kappaB) activation. Fermented guava leaf extract significantly inhibited LPS-induced NF-kappaB transcriptional activity. Immunochemical analysis revealed that fermented guava leaf extract suppressed LPS-induced degradation of I-kappaBalpha. Taken together, the data indicate that fermented guava leaf extract is involved in the inhibition of iNOS and COX-2 via the down-regulation of NF-kappaB pathway, revealing a partial molecular basis for the antiinflammatory properties of fermented guava leaf extract.

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.

An Attempt to Derive the epsilon Equation from a Two-Point Closure

NASA Technical Reports Server (NTRS)

Canuto, V. M.; Cheng, Y.; Howard, A. M.

2010-01-01

The goal of this paper is to derive the equation for the turbulence dissipation rate epsilon for a shear-driven flow. In 1961, Davydov used a one-point closure model to derive the epsilon equation from first principles but the final result contained undetermined terms and thus lacked predictive power. Both in 1987 and in 2001, attempts were made to derive the epsilon equation from first principles using a two-point closure, but their methods relied on a phenomenological assumption. The standard practice has thus been to employ a heuristic form of the equation that contains three empirical ingredients: two constants, c(sub 1 epsilon), and c(sub 2 epsilon), and a diffusion term D(sub epsilon) In this work, a two-point closure is employed, yielding the following results: 1) the empirical constants get replaced by c(sub 1), c(sub 2), which are now functions of Kappa and epsilon; 2) c(sub 1) and c(sub 2) are not independent because a general relation between the two that are valid for any Kappa and epsilon are derived; 3) c(sub 1), c(sub 2) become constant with values close to the empirical values c(sub 1 epsilon), c(sub epsilon 2), (i.e., homogenous flows); and 4) the empirical form of the diffusion term D(sub epsilon) is no longer needed because it gets substituted by the Kappa-epsilon dependence of c(sub 1), c(sub 2), which plays the role of the diffusion, together with the diffusion of the turbulent kinetic energy D(sub Kappa), which now enters the new equation (i.e., inhomogeneous flows). Thus, the three empirical ingredients c(sub 1 epsilon), c(sub epsilon 2), D (sub epsilon)are replaced by a single function c(sub 1)(Kappa, epsilon ) or c(sub 2)(Kappa, epsilon ), plus a D(sub Kappa)term. Three tests of the new equation for epsilon are presented: one concerning channel flow and two concerning the shear-driven planetary boundary layer (PBL).

Inter-rater and intra-rater agreement on the Nordic Orofacial Test--Screening examination in children, adolescents and young adults with cerebral palsy.

PubMed

Edvinsson, Siv Elisabet; Lundqvist, Lars-Olov

2014-02-01

To evaluate inter-rater and intra-rater agreement on the Nordic Orofacial Test-Screening (NOT-S) examination applied to children, adolescents and young adults with cerebral palsy (CP). Using the NOT-S examination, two speech and language pathologists independently assessed video recordings of 48 subjects with CP aged 5-22 years and representing all CP sub-diagnoses and levels of gross motor function and manual ability. Thirty-one subjects were reassessed. Fifteen out of 17 items in the NOT-S examination domains (1) Face at rest, (2) Nose breathing, (3) Facial expression, (4) Masticatory muscle and jaw function, (5) Oral motor function and (6) Speech were rated using a 'yes' (dysfunction observed)/'no' format, generating an overall score of 0-6. Inter-rater agreement: Twelve out of 15 items and five out of six domains showed acceptable unweighted kappa values (κ = 0.46-1.00). The lowest kappa value was found for domain 4 (κ = -0.04), although it had high inter-rater agreement (92%). The linear weighted kappa value for the overall NOT-S examination score was 0.65 (95% CI = 0.49-0.82). Intra-rater agreement: All items and domains showed acceptable unweighted kappa values (items 0.58-1.00 and 0.59-1.00, domains 0.81-1.00 and 0.62-0.89) for both raters. The linear weighted kappa value for the overall NOT-S examination score was 0.81 (95% CI = 0.63-0.99) for rater A and 0.54 (95% CI = 0.25-0.82) for rater B. The NOT-S examination has acceptable inter-rater and intra-rater agreement when used in young individuals with CP.

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.

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.

Dielectric cytometry with three-dimensional cellular modeling.

PubMed

Katsumoto, Yoichi; Hayashi, Yoshihito; Oshige, Ikuya; Omori, Shinji; Kishii, Noriyuki; Yasuda, Akio; Asami, Koji

2008-09-15

We have developed what we believe is an efficient method to determine the electric parameters (the specific membrane capacitance C(m) and the cytoplasm conductivity kappa(i)) of cells from their dielectric dispersion. First, a limited number of dispersion curves are numerically calculated for a three-dimensional cell model by changing C(m) and kappa(i), and their amplitudes Deltaepsilon and relaxation times tau are determined by assuming a Cole-Cole function. Second, regression formulas are obtained from the values of Deltaepsilon and tau and then used for the determination of C(m) and kappa(i) from the experimental Deltaepsilon and tau. This method was applied to the dielectric dispersion measured for rabbit erythrocytes (discocytes and echinocytes) and human erythrocytes (normocytes), and provided reasonable C(m) and kappa(i) of the erythrocytes and excellent agreement between the theoretical and experimental dispersion curves.

Negative regulation of protein phosphatase 2Cbeta by ISG15 conjugation.

PubMed

Takeuchi, Tomoharu; Kobayashi, Takayasu; Tamura, Shinri; Yokosawa, Hideyoshi

2006-08-07

ISG15, an interferon-upregulated ubiquitin-like protein, is covalently conjugated to various cellular proteins (ISGylation). In this study, we found that protein phosphatase 2Cbeta (PP2Cbeta), which functions in the nuclear factor kappaB (NF-kappaB) pathway via dephosphorylation of TGF-beta-activated kinase, was ISGylated, and analysis by NF-kappaB luciferase reporter assay revealed that PP2Cbeta activity was suppressed by co-expression of ISG15, UBE1L, and UbcH8. We determined the ISGylation sites of PP2Cbeta and constructed its ISGylation-resistant mutant. In contrast to the wild type, this mutant suppressed the NF-kappaB pathway even in the presence of ISG15, UBE1L, and UbcH8. Thus, we propose that ISGylation negatively regulates PP2Cbeta activity.

Effects of dynamic long-period ocean tides on changes in earth's rotation rate

NASA Technical Reports Server (NTRS)

Nam, Young; Dickman, S. R.

1990-01-01

As a generalization of the zonal response coefficient first introduced by Agnew and Farrell (1978), the zonal response function kappa of the solid earth-ocean system is defined as the ratio, in the frequency domain, of the tidal change in earth's rotation rate to the tide-generating potential. Amplitudes and phases of kappa for the monthly, fortnightly, and nine-day lunar tides are estimated from 2 1/2 years of VLBI UT1 observations, corrected for atmospheric angular momentum effects using NMC wind and pressure series. Using the dynamic ocean tide model of Dickman (1988, 1989), amplitudes and phases of kappa for an elastic earth-ocean system are predicted. The predictions confirm earlier results which found that dynamic effects of the longer-period ocean tides reduce the amplitude of kappa by about 1 percent.

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.

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

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 clastic rocks reported in previously measured sections of the Phi Kappa, as well as the sequence along Phi Kappa Creek from which the name originates, are excluded from the Phi Kappa as revised and are reassigned to two structural plates of Mississippian Copper Basin Formation; other strata now excluded from the formation are reassigned to the Trail Creek Formation and to an unnamed Silurian and Devonian unit. As redefined, the Phi Kappa Formation is only about 240 m thick, compared with the 3,860 m originally estimated, and it occupies only about 25 percent of the outcrop area previously mapped in 1930 by H. G. Westgate and C. P. Ross. Despite this drastic reduction in thickness and the exclusion of the rocks along Phi Kappa Creek, the name Phi Kappa is retained because of widely accepted prior usage to denote the Ordovician graptolitic shale facies of central Idaho, and because the Phi Kappa Formation as revised is present in thrust slices on Phi Kappa Mountain, at the head of Phi Kappa Creek. The lithic and faunal consistency of this unit throughout the area precludes the necessity for major facies telescoping along individual faults within the outcrop belt. However, tens of kilometers of tectonic shortening seems required to juxtapose the imbricated Phi Kappa shale facies with the Middle Ordovician part of the carbonate and quartzite shale sequence of east central Idaho. The shelf rocks are exposed in the Wildhorse structural window of the northeastern Pioneer Mountains, and attain a thickness of at least 1,500 m throughout the region north and east of the Pioneer Mountains. The Phi Kappa is in direct thrust contact on intensely deformed medium- to high-grade metamorphic equivalents of the same shelf sequence in the Pioneer window at the south end of the Phi Kappa-Trail Creek outcrop belt. Along East Pass, Big Lake, and Pine Creeks, north of the Pioneer Mountains, some rocks previously mapped as Ramshorn Slate are lithologically and faunally equivalent to the P

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.

Representation of the Geosynchronous Plasma Environment in Spacecraft Charging Calculations

NASA Technical Reports Server (NTRS)

Davis, V. A.; Mandell, M. J.; Thomsen, M. F.

2006-01-01

Historically, our ability to predict and postdict spacecraft surface charging has been limited by the characterization of the plasma environment. One difficulty lies in the common practice of fitting the plasma data to a Maxwellian or Double Maxwellian distribution function, which may not represent the data well for charging purposes. We use electron and ion flux spectra measured by the Los Alamos National Laboratory (LANL) Magnetospheric Plasma Analyzer (MPA) to examine how the use of different spectral representations of the charged particle environment in computations of spacecraft potentials during magnetospheric substorms affects the accuracy of the results. We calculate the spacecraft potential using both the measured fluxes and several different fits to these fluxes. These measured fluxes have been corrected for the difference between the measured and calculated potential. The potential computed using the measured fluxes and the best available material properties of graphite carbon, with a secondary electron escape fraction of 81%, is within a factor of three of the measured potential for 87% of the data. Potentials calculated using a Kappa function fit to the incident electron flux distribution function and a Maxwellian function fit to the incident ion flux distribution function agree with measured potentials nearly as well as do potentials calculated using the measured fluxes. Alternative spectral representations gave less accurate estimates of potential. The use of all the components of the net flux, along with spacecraft specific average material properties, gives a better estimate of the spacecraft potential than the high energy flux alone.

Log-Linear Modeling of Agreement among Expert Exposure Assessors

PubMed Central

Hunt, Phillip R.; Friesen, Melissa C.; Sama, Susan; Ryan, Louise; Milton, Donald

2015-01-01

Background: Evaluation of expert assessment of exposure depends, in the absence of a validation measurement, upon measures of agreement among the expert raters. Agreement is typically measured using Cohen’s Kappa statistic, however, there are some well-known limitations to this approach. We demonstrate an alternate method that uses log-linear models designed to model agreement. These models contain parameters that distinguish between exact agreement (diagonals of agreement matrix) and non-exact associations (off-diagonals). In addition, they can incorporate covariates to examine whether agreement differs across strata. Methods: We applied these models to evaluate agreement among expert ratings of exposure to sensitizers (none, likely, high) in a study of occupational asthma. Results: Traditional analyses using weighted kappa suggested potential differences in agreement by blue/white collar jobs and office/non-office jobs, but not case/control status. However, the evaluation of the covariates and their interaction terms in log-linear models found no differences in agreement with these covariates and provided evidence that the differences observed using kappa were the result of marginal differences in the distribution of ratings rather than differences in agreement. Differences in agreement were predicted across the exposure scale, with the likely moderately exposed category more difficult for the experts to differentiate from the highly exposed category than from the unexposed category. Conclusions: The log-linear models provided valuable information about patterns of agreement and the structure of the data that were not revealed in analyses using kappa. The models’ lack of dependence on marginal distributions and the ease of evaluating covariates allow reliable detection of observational bias in exposure data. PMID:25748517

The Fn14 cytoplasmic tail binds tumour-necrosis-factor-receptor-associated factors 1, 2, 3 and 5 and mediates nuclear factor-kappaB activation.

PubMed Central

Brown, Sharron A N; Richards, Christine M; Hanscom, Heather N; Feng, Sheau-Line Y; Winkles, Jeffrey A

2003-01-01

Fn14 is a growth-factor-inducible immediate-early-response gene encoding a 102-amino-acid type I transmembrane protein. The human Fn14 protein was recently identified as a cell-surface receptor for the tumour necrosis factor (TNF) superfamily member named TWEAK (TNF-like weak inducer of apoptosis). In the present paper, we report that the human TWEAK extracellular domain can also bind the murine Fn14 protein. Furthermore, site-specific mutagenesis and directed yeast two-hybrid interaction assays revealed that the TNFR-associated factor (TRAF) 1, 2, 3 and 5 adaptor molecules bind the murine Fn14 cytoplasmic tail at an overlapping, but non-identical, amino acid sequence motif. We also found that TWEAK treatment of quiescent NIH 3T3 cells stimulates inhibitory kappaBalpha phosphorylation and transcriptional activation of a nuclear factor-kappaB (NF-kappaB) enhancer/luciferase reporter construct. Fn14 overexpression in transiently transfected NIH 3T3 cells also promotes NF-kappaB activation, and this cellular response requires an intact TRAF binding site. These results indicate that Fn14 is a functional TWEAK receptor that can associate with four distinct TRAF family members and stimulate the NF-kappaB transcription factor signalling pathway. PMID:12529173

Modulation of NF-kappaB activation in Theileria annulata-infected cloned cell lines is associated with detection of parasite-dependent IKK signalosomes and disruption of the actin cytoskeleton.

PubMed

Schmuckli-Maurer, Jacqueline; Kinnaird, Jane; Pillai, Sreerekha; Hermann, Pascal; McKellar, Sue; Weir, William; Dobbelaere, Dirk; Shiels, Brian

2010-02-01

Apicomplexan parasites within the genus Theileria have the ability to induce continuous proliferation and prevent apoptosis of the infected bovine leukocyte. Protection against apoptosis involves constitutive activation of the bovine transcription factor NF-kappaB in a parasite-dependent manner. Activation of NF-kappaB is thought to involve recruitment of IKK signalosomes at the surface of the macroschizont stage of the parasite, and it has been postulated that additional host proteins with adaptor or scaffolding function may be involved in signalosome formation. In this study two clonal cell lines were identified that show marked differences in the level of activated NF-kappaB. Further characterization of these lines demonstrated that elevated levels of activated NF-kappaB correlated with increased resistance to cell death and detection of parasite-associated IKK signalosomes, supporting results of our previous studies. Evidence was also provided for the existence of host- and parasite-dependent NF-kappaB activation pathways that are influenced by the architecture of the actin cytoskeleton. Despite this influence, it appears that the primary event required for formation of the parasite-dependent IKK signalosome is likely to be an interaction between a signalosome component and a parasite-encoded surface ligand.

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

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.

Microfluidic diffusion diluter: bulging of PDMS microchannels under pressure-driven flow

NASA Astrophysics Data System (ADS)

Holden, Matthew A.; Kumar, Saurabh; Beskok, Ali; Cremer, Paul S.

2003-05-01

The bulging of microfluidic systems during pressure-driven flow is potentially a major consideration for polydimethylsiloxane (PDMS)-based devices. Microchannel cross-sectional areas can change drastically as a function of flow rate and downstream microchannel position. Such geometrical flexibility leads to difficulties in predicting convective/diffusive transport for these systems. We have previously introduced a non-dimensional parameter, kappa, for characterizing convection and diffusion behavior for pressure-driven flow in rigid all-glass systems. This paper describes a modification of that concept for application to non-rigid systems, which is accomplished by incorporating an experimental step to account for the bulging in PDMS/glass microsystems. Specifically, an experimental measurement of channel height by fluorescence microscopy is combined with the aforementioned theory to characterize convective/diffusive behavior at a single location in the device. This allowed the parameter kappa to be determined at that point and applied to predict fluid flow in the subsequent portion of the PDMS microsystem. This procedure was applied to a PDMS/glass microfluidic diffusion dilution (muDD) device designed for generating concentration gradients. Theoretically predicted and experimentally measured distributions of concentrations within the microsystem matched well.

Molecular dynamics simulation of polymer electrolytes based on poly(ethylene oxide) and ionic liquids. II. Dynamical properties.

PubMed

Costa, Luciano T; Ribeiro, Mauro C C

2007-10-28

Dynamical properties of polymer electrolytes based on poly(ethylene oxide) (PEO) and ionic liquids of 1-alkyl-3-methylimidazolium cations were calculated by molecular dynamics simulations with previously proposed models [L. T. Costa and M. C. Ribeiro, J. Chem. Phys. 124, 184902 (2006)]. The effect of changing the ionic liquid concentration, temperature, and the 1-alkyl-chain lengths, [1,3-dimethylimidazolium]PF(6) and [1-butyl-3-methylimidazolium]PF(6) ([dmim]PF(6) and [bmim]PF(6)), was investigated. Cation diffusion coefficient is higher than those of anion and oxygen atoms of PEO chains. Ionic mobility in PEO[bmim]PF(6) is higher than in PEO[dmim]PF(6), so that the ionic conductivity kappa of the former is approximately ten times larger than the latter. The ratio between kappa and its estimate from the Nernst-Einstein equation kappa/kappa(NE), which is inversely proportional to the strength of ion pairs, is higher in ionic liquid polymer electrolytes than in polymer electrolytes based on inorganic salts with Li(+) cations. Calculated time correlation functions corroborate previous evidence from the analysis of equilibrium structure that the ion pairs in ionic liquid polymer electrolytes are relatively weak. Structural relaxation at distinct spatial scales is revealed by the calculation of the intermediate scattering function at different wavevectors. These data are reproduced with stretched exponential functions, so that temperature and wavevector dependences of best fit parameters can be compared with corresponding results for polymer electrolytes containing simpler ions.

Stimulation of interleukin-13 expression by human T-cell leukemia virus type 1 oncoprotein Tax via a dually active promoter element responsive to NF-kappaB and NFAT.

PubMed

Silbermann, Katrin; Schneider, Grit; Grassmann, Ralph

2008-11-01

The human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein transforms human lymphocytes and is critical for the pathogenesis of HTLV-1-induced adult T-cell leukaemia. In HTLV-transformed cells, Tax upregulates interleukin (IL)-13, a cytokine with proliferative and anti-apoptotic functions that is linked to leukaemogenesis. Tax-stimulated IL-13 is thought to result in autocrine stimulation of HTLV-infected cells and thus may be relevant to their growth. The causal transactivation of the IL-13 promoter by Tax is predominantly dependent on a nuclear factor of activated T cells (NFAT)-binding P element. Here, it was shown that the isolated IL-13 Tax-responsive element (IL13TaxRE) was sufficient to mediate IL-13 transactivation by Tax and NFAT1. However, cyclosporin A, a specific NFAT inhibitor, revealed that Tax transactivation of IL13TaxRE or wild-type IL-13 promoter was independent of NFAT and that NFAT did not contribute to IL-13 upregulation in HTLV-transformed cells. By contrast, Tax stimulation was repressible by an efficient nuclear factor (NF)-kappaB inhibitor (IkBaDN), indicating the requirement for NF-kappaB. The capacity of NF-kappaB to stimulate IL13TaxRE was demonstrated by a strong response to NF-kappaB in reporter assays and by direct binding of NF-kappaB to IL13TaxRE. Thus, IL13TaxRE in the IL-13 promoter represents a dually active promoter element responsive to NF-kappaB and NFAT. Together, these results indicate that Tax causes IL-13 upregulation in HTLV-1-infected cells via NF-kappaB.

Inactivation of IkappaBbeta by the tax protein of human T-cell leukemia virus type 1: a potential mechanism for constitutive induction of NF-kappaB.

PubMed

McKinsey, T A; Brockman, J A; Scherer, D C; Al-Murrani, S W; Green, P L; Ballard, D W

1996-05-01

In resting T lymphocytes, the transcription factor NF-kappaB is sequestered in the cytoplasm via interactions with members of the I kappa B family of inhibitors, including IkappaBalpha and IkappaBbeta. During normal T-cell activation, IkappaBalpha is rapidly phosphorylated, ubiquitinated, and degraded by the 26S proteasome, thus permitting the release of functional NF-kappaB. In contrast to its transient pattern of nuclear induction during an immune response, NF-kappaB is constitutively activated in cells expressing the Tax transforming protein of human T-cell leukemia virus type I (HTLV-1). Recent studies indicate that HTLV-1 Tax targets IkappaBalpha to the ubiquitin-proteasome pathway. However, it remains unclear how this viral protein induces a persistent rather than transient NF-kappaB response. In this report, we provide evidence that in addition to acting on IkappaBalpha, Tax stimulates the turnover Of IkappaBbeta via a related targeting mechanism. Like IkappaBalpha, Tax-mediated breakdown of IkappaBbeta in transfected T lymphocytes is blocked either by cell-permeable proteasome inhibitors or by mutation Of IkappaBbeta at two serine residues present within its N-terminal region. Despite the dual specificity of HTLV-1 Tax for IkappaBalpha and IkappaBbeta at the protein level, Tax selectively stimulates NF-kappaB-directed transcription of the IkappaBalpha gene. Consequently, IkappaBbeta protein expression is chronically downregulated in HTLV-1-infected T lymphocytes. These findings with IkappaBbeta provide a potential mechanism for the constitutive activation of NF-kappaB in Tax-expressing cells.

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

The active movement scale: an evaluative tool for infants with obstetrical brachial plexus palsy.

PubMed

Curtis, Christine; Stephens, Derek; Clarke, Howard M; Andrews, David

2002-05-01

Newborns with peripheral nerve lesions involving the upper extremity are difficult to evaluate. The reliability of the Active Movement Scale (AMS), a tool for assessing motor function in infants with obstetrical brachial plexus palsy (OBPP), was examined in 2 complementary studies. Part A was an interrater reliability study in which 63 infants younger than 1 year with OBPP were independently evaluated by 2 physical therapists using the AMS. The scores were compared for reliability and controlled for chance agreement by using kappa statistics. Overall kappa analysis of the 15 tested movements showed a moderate strength of score agreement (kappa = 0.51). Quadratic-weighted kappa (kappa(quad)) statistics showed that 8 of the 15 movements tested were in the highest strength of agreement category (kappa(quad) = 0.81-1.00). Five movements showed substantial agreement (kappa(quad) = 0.61-0.80), and 2 movements had moderate agreement (kappa(quad) = 0.41- 0.60). The overall kappa(quad) was 0.89. Part B was a variability study designed to examine the dispersion of scores when infants with OBPP were evaluated with the AMS by multiple raters. Ten pediatric physical therapists with varying degrees of experience using the scale attended a 1(1/2)-hour instructional workshop on administration of the tool for infants with OBPP. A chain-block study design was used to obtain 30 assessments of 10 infants by 10 raters. A 2-way analysis of variance indicated that the variability of scores due to rater factors was low compared with the variability due to patient factors and that variation in scores due to rater experience was minimal. The results of part A indicate that the AMS is a reliable tool for the assessment of infants with OBPP when raters familiar with the scale are compared. The results of part B suggest that, with minimal training, raters with a range of experience using the AMS are able to reliably evaluate infants with upper-extremity paralysis.

Ectoderm-targeted overexpression of the glucocorticoid receptor induces hypohidrotic ectodermal dysplasia.

PubMed

Cascallana, Jose Luis; Bravo, Ana; Donet, Eva; Leis, Hugo; Lara, Maria Fernanda; Paramio, Jesús M; Jorcano, José L; Pérez, Paloma

2005-06-01

Hypohidrotic ectodermal dysplasia is a human syndrome defined by maldevelopment of one or more ectodermal-derived tissues, including the epidermis and cutaneous appendices, teeth, and exocrine glands. The molecular bases of this pathology converge in a dysfunction of the transcription factor nuclear factor of the kappa-enhancer in B cells (NF-kappaB), which is essential to epithelial homeostasis and development. A number of mouse models bearing disruptions in NF-kappaB signaling have been reported to manifest defects in ectodermal derivatives. In ectoderm-targeted transgenic mice overexpressing the glucocorticoid receptor (GR) [keratin 5 (K5)-GR mice], the NF-kappaB activity is greatly decreased due to functional antagonism between GR and NF-kappaB. Here, we report that K5-GR mice exhibit multiple epithelial defects in hair follicle, tooth, and palate development. Additionally, these mice lack Meibomian glands and display underdeveloped sweat and preputial glands. These phenotypic features appear to be mediated specifically by ligand-activated GR because the synthetic analog dexamethasone induced similar defects in epithelial morphogenesis, including odontogenesis, in wild-type mice. We have focused on tooth development in K5-GR mice and found that an inhibitor of steroid synthesis partially reversed the abnormal phenotype. Immunostaining revealed reduced expression of the inhibitor of kappaB kinase subunits, IKKalpha and IKKgamma, and diminished p65 protein levels in K5-GR embryonic tooth, resulting in a significantly reduced kappaB-binding activity. Remarkably, altered NF-kappaB activity elicited by GR overexpression correlated with a dramatic decrease in the protein levels of DeltaNp63 in tooth epithelia without affecting Akt, BMP4, or Foxo3a. Given that many of the 170 clinically distinct ectodermal dysplasia syndromes still remain without cognate genes, deciphering the molecular mechanisms of this mouse model with epithelial NF-kappaB and p63 dysfunction may provide important clues to understanding the basis of other ectodermal dysplasia syndromes.

Donor Preconditioning After the Onset of Brain Death With Dopamine Derivate n-Octanoyl Dopamine Improves Early Posttransplant Graft Function in the Rat.

PubMed

Li, S; Korkmaz-Icöz, S; Radovits, T; Ruppert, M; Spindler, R; Loganathan, S; Hegedűs, P; Brlecic, P; Theisinger, B; Theisinger, S; Höger, S; Brune, M; Lasitschka, F; Karck, M; Yard, B; Szabó, G

2017-07-01

Heart transplantation is the therapy of choice for end-stage heart failure. However, hemodynamic instability, which has been demonstrated in brain-dead donors (BDD), could also affect the posttransplant graft function. We tested the hypothesis that treatment of the BDD with the dopamine derivate n-octanoyl-dopamine (NOD) improves donor cardiac and graft function after transplantation. Donor rats were given a continuous intravenous infusion of either NOD (0.882 mg/kg/h, BDD+NOD, n = 6) or a physiological saline vehicle (BDD, n = 9) for 5 h after the induction of brain death by inflation of a subdural balloon catheter. Controls were sham-operated (n = 9). In BDD, decreased left-ventricular contractility (ejection fraction; maximum rate of rise of left-ventricular pressure; preload recruitable stroke work), relaxation (maximum rate of fall of left-ventricular pressure; Tau), and increased end-diastolic stiffness were significantly improved after the NOD treatment. Following the transplantation, the NOD-treatment of BDD improved impaired systolic function and ventricular relaxation. Additionally, after transplantation increased interleukin-6, tumor necrosis factor TNF-α, NF-kappaB-p65, and nuclear factor (NF)-kappaB-p105 gene expression, and increased caspase-3, TNF-α and NF-kappaB protein expression could be significantly downregulated by the NOD treatment compared to BDD. BDD postconditioning with NOD through downregulation of the pro-apoptotic factor caspase-3, pro-inflammatory cytokines, and NF-kappaB may protect the heart against the myocardial injuries associated with brain death and ischemia/reperfusion. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

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.

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.

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.

Inter-rater reliability of the Sødring Motor Evaluation of Stroke patients (SMES).

PubMed

Halsaa, K E; Sødring, K M; Bjelland, E; Finsrud, K; Bautz-Holter, E

1999-12-01

The Sødring Motor Evaluation of Stroke patients is an instrument for physiotherapists to evaluate motor function and activities in stroke patients. The rating reflects quality as well as quantity of the patient's unassisted performance within three domains: leg, arm and gross function. The inter-rater reliability of the method was studied in a sample of 30 patients admitted to a stroke rehabilitation unit. Three therapists were involved in the study; two therapists assessed the same patient on two consecutive days in a balanced design. Cohen's weighted kappa and McNemar's test of symmetry were used as measures of item reliability, and the intraclass correlation coefficient was used to express the reliability of the sumscores. For 24 out of 32 items the weighted kappa statistic was excellent (0.75-0.98), while 7 items had a kappa statistic within the range 0.53-0.74 (fair to good). The reliability of one item was poor (0.13). The intraclass correlation coefficient for the three sumscores was 0.97, 0.91 and 0.97. We conclude that the Sødring Motor Evaluation of Stroke patients is a reliable measure of motor function in stroke patients undergoing rehabilitation.

Floating phase in the one-dimensional transverse axial next-nearest-neighbor Ising model.

PubMed

Chandra, Anjan Kumar; Dasgupta, Subinay

2007-02-01

To study the ground state of an axial next-nearest-neighbor Ising chain under transverse field as a function of frustration parameter kappa and field strength Gamma, we present here two different perturbative analyses. In one, we consider the (known) ground state at kappa=0.5 and Gamma=0 as the unperturbed state and treat an increase of the field from 0 to Gamma coupled with an increase of kappa from 0.5 to 0.5+rGamma/J as perturbation. The first-order perturbation correction to eigenvalue can be calculated exactly and we could conclude that there are only two phase-transition lines emanating from the point kappa=0.5, Gamma=0. In the second perturbation scheme, we consider the number of domains of length 1 as the perturbation and obtain the zeroth-order eigenfunction for the perturbed ground state. From the longitudinal spin-spin correlation, we conclude that floating phase exists for small values of transverse field over the entire region intermediate between the ferromagnetic phase and antiphase.

Nonguiding Center Motion and Substorm Effects in the Magnetotail

NASA Technical Reports Server (NTRS)

Kaufmann, Richard L.; Kontodinas, Ioannis D.; Ball, Bryan M.; Larson, Douglas J.

1997-01-01

Thick and thin models of the middle magnetotail were developed using a consistent orbit tracing technique. It was found that currents carried near the equator by groups of ions with anisotropic distribution functions are not well approximated by the guiding center expressions. The guiding center equations fail primarily because the calculated pressure tensor is not magnetic field aligned. The pressure tensor becomes field aligned as one moves away from the equator, but here there is a small region in which the guiding center equations remain inadequate because the two perpendicular components of the pressure tensor are unequal. The significance of nonguiding center motion to substorm processes then was examined. One mechanism that may disrupt a thin cross-tail current sheet involves field changes that cause ions to begin following chaotic orbits. The lowest-altitude chaotic region, characterized by an adiabaticity parameter kappa approx. equal to 0.8, is especially important. The average cross-tail particle drift is slow, and we were unable to generate a thin current sheet using such ions. Therefore, any process that tends to create a thin current sheet in a region with kappa approaching 0.8 may cause the cross-tail current to get so low that it becomes insufficient to support the lobes. A different limit may be important in resonant orbit regions of a thin current sheet because particles reach a maximum cross-tail drift velocity. If the number of ions per unit length decreases as the tail is stretched, this part of the plasma sheet also may become unable to carry the cross-tail current needed to support the lobes. Thin sheets are needed for both resonant and chaotic orbit mechanisms because the distribution function must be highly structured. A description of current continuity is included to show how field aligned currents can evolve during the transition from a two-dimensional (2-D) to a 3-D configuration.

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.

Evaluation of NF-B Signaling in T Cells

DTIC Science & Technology

2009-01-01

of cancer cells, ranging from myelomas (46) to breast cancer (47) to esophageal cancer (48), to name a few. NF-κB activation is also implicated in...Sonenshein. 1997. Aberrant nuclear factor-kappaB/Rel expression and the pathogenesis of breast cancer . J Clin Invest 100:2952-2960. 48. Abdel-Latif, M... Cancer Res 3:345-353. 43. Hinz, M., D. Krappmann, A. Eichten, A. Heder, C. Scheidereit, and M. Strauss. 1999. NF-kappaB function in growth control

Magnetosonic Solitons in Non-Maxwellian Space Plasmas

NASA Astrophysics Data System (ADS)

Pokhotelov, O. A.; Balikhin, M.; Onishchenko, O. G.

2006-12-01

The nonlinear theory of large-amplitude magnetosonic (MS) waves in high-beta space plasmas is developed. It is shown that solitary waves can exist in the form of magnetic humps and holes in which the magnetic field is increased or decreased relative to the background magnetic field. This depends on the shape of the equilibrium ion velocity distribution function. The basic parameter that controls the nonlinear structure is the wave dispersion which can be either positive or negative. A general dispersion relation for MS waves propagating perpendicularly to the external magnetic field in a plasma with an arbitrary velocity distribution function is derived. It takes into account general plasma equilibria such as the Dory-Guest-Harris or Kennel- Ashour-Abdalla loss cone equilibria, as well as distributions with a power law velocity dependence that can be modelled by kappa-distributions. It is shown that in Maxwellian and bi-Maxwellian plasmas the dispersion is negative, i.e. the phase velocity decreases with an increase of the wave number. This means that the solitary solution in this case has the form of a magnetic hump with the magnetic field increased. On the contrary, in some non-Maxwellian plasmas such as those with ring-type ion distributions or DGH plasmas, the solitary solution may have the form of a magnetic hole. The results of similar investigations based on nonlinear Hall-MHD equations are reviewed. The relevance of our theoretical results to experimental observations is outlined

Ethyl caffeate suppresses NF-kappaB activation and its downstream inflammatory mediators, iNOS, COX-2, and PGE2 in vitro or in mouse skin.

PubMed

Chiang, Yi-Ming; Lo, Chiu-Ping; Chen, Yi-Ping; Wang, Sheng-Yang; Yang, Ning-Sun; Kuo, Yueh-Hsiung; Shyur, Lie-Fen

2005-10-01

Ethyl caffeate, a natural phenolic compound, was isolated from Bidens pilosa, a medicinal plant popularly used for treating certain inflammatory syndromes. The purpose of this study was to investigate the structural activity, and the anti-inflammatory functions and mechanism(s) of ethyl caffeate. Ethyl caffeate was found to markedly suppress the lipopolysaccharide (LPS)-induced nitric oxide (NO) production (IC(50) = 5.5 microg ml(-1)), mRNA and protein expressions of inducible nitric oxide synthase (iNOS), and prostaglandin E(2) (PGE(2)) production in RAW 264.7 macrophages. Transient gene expression assays using human cox-2 promoter construct revealed that ethyl caffeate exerted an inhibitory effect on cox-2 transcriptional activity in 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated MCF-7 cells. Immunohistochemical studies of mouse skin demonstrated that TPA-induced COX-2 expression was significantly inhibited by ethyl caffeate with a superior effect to that of celecoxib, a nonsteroidal anti-inflammatory drug. The phosphorylation and degradation of inhibitor kappaB (IkappaB) and the translocation of nuclear transcription factor-kappaB (NF-kappaB) into the nucleus, as well as the activation of mitogen-activated protein kinases (MAPKs) induced by LPS in macrophages, were not affected by ethyl caffeate. Ethyl caffeate, however, could inhibit NF-kappaB activation by impairing the binding of NF-kappaB to its cis-acting element. These results suggest that ethyl caffeate suppresses iNOS and COX-2 expressions partly through the inhibition of the NF-kappaB.DNA complex formation. Structure-activity relationship analyses suggested that the catechol moiety and alpha,beta-unsaturated ester group in ethyl caffeate are important and essential structural features for preventing NF-kappaB.DNA complex formation. This study provides an insight into the probable mechanism(s) underlying the anti-inflammatory and therapeutic properties of ethyl caffeate.

Leptin-induced IL-6 production is mediated by leptin receptor, insulin receptor substrate-1, phosphatidylinositol 3-kinase, Akt, NF-kappaB, and p300 pathway in microglia.

PubMed

Tang, Chih-Hsin; Lu, Da-Yuu; Yang, Rong-Sen; Tsai, Huei-Yann; Kao, Ming-Ching; Fu, Wen-Mei; Chen, Yuh-Fung

2007-07-15

Leptin, the adipocyte-secreted hormone that centrally regulates weight control, is known to function as an immunomodulatory regulator. We investigated the signaling pathway involved in IL-6 production caused by leptin in microglia. Microglia expressed the long (OBRl) and short (OBRs) isoforms of the leptin receptor. Leptin caused concentration- and time-dependent increases in IL-6 production. Leptin-mediated IL-6 production was attenuated by OBRl receptor antisense oligonucleotide, PI3K inhibitor (Ly294002 and wortmannin), Akt inhibitor (1L-6-hydroxymethyl-chiro-inositol-2-((R)-2-O-methyl-3-O-octadecylcarbonate)), NF-kappaB inhibitor (pyrrolidine dithiocarbamate), IkappaB protease inhibitor (L-1-tosylamido-2-phenylenylethyl chloromethyl ketone), IkappaBalpha phosphorylation inhibitor (Bay 117082), or NF-kappaB inhibitor peptide. Transfection with insulin receptor substrate (IRS)-1 small-interference RNA or the dominant-negative mutant of p85 and Akt also inhibited the potentiating action of leptin. Stimulation of microglia with leptin activated IkappaB kinase alpha/IkappaB kinase beta, IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 phosphorylation at Ser(276), p65 and p50 translocation from the cytosol to the nucleus, and kappaB-luciferase activity. Leptin-mediated an increase of IkappaB kinase alpha/IkappaB kinase beta activity, kappaB-luciferase activity, and p65 and p50 binding to the NF-kappaB element was inhibited by wortmannin, Akt inhibitor, and IRS-1 small-interference RNA. The binding of p65 and p50 to the NF-kappaB elements, as well as the recruitment of p300 and the enhancement of histone H3 and H4 acetylation on the IL-6 promoter was enhanced by leptin. Our results suggest that leptin increased IL-6 production in microglia via the leptin receptor/IRS-1/PI3K/Akt/NF-kappaB and p300 signaling pathway.

Constitutive activation of NF-kappa B and secretion of interleukin-8 induced by the G protein-coupled receptor of Kaposi's sarcoma-associated herpesvirus involve G alpha(13) and RhoA.

PubMed

Shepard, L W; Yang, M; Xie, P; Browning, D D; Voyno-Yasenetskaya, T; Kozasa, T; Ye, R D

2001-12-07

The Kaposi's sarcoma herpesvirus (KSHV) open reading frame 74 encodes a G protein-coupled receptor (GPCR) for chemokines. Exogenous expression of this constitutively active GPCR leads to cell transformation and vascular overgrowth characteristic of Kaposi's sarcoma. We show here that expression of KSHV-GPCR in transfected cells results in constitutive transactivation of nuclear factor kappa B (NF-kappa B) and secretion of interleukin-8, and this response involves activation of G alpha(13) and RhoA. The induced expression of a NF-kappa B luciferase reporter was partially reduced by pertussis toxin and the G beta gamma scavenger transducin, and enhanced by co-expression of G alpha(13) and to a lesser extent, G alpha(q). These results indicate coupling of KSHV-GPCR to multiple G proteins for NF-kappa B activation. Expression of KSHV-GPCR led to stress fiber formation in NIH 3T3 cells. To examine the involvement of the G alpha(13)-RhoA pathway in KSHV-GPCR-mediated NF-kappa B activation, HeLa cells were transfected with KSHV-GPCR alone and in combination with the regulator of G protein signaling (RGS) from p115RhoGEF or a dominant negative RhoA(T19N). Both constructs, as well as the C3 exoenzyme from Clostritium botulinum, partially reduced NF-kappa B activation by KSHV-GPCR, and by a constitutively active G alpha(13)(Q226L). KSHV-GPCR-induced NF-kappa B activation is accompanied by increased secretion of IL-8, a function mimicked by the activated G alpha(13) but not by an activated G alpha(q)(Q209L). These results suggest coupling of KSHV-GPCR to the G alpha(13)-RhoA pathway in addition to other G proteins.

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) .

CIKS, a connection to Ikappa B kinase and stress-activated protein kinase.

PubMed

Leonardi, A; Chariot, A; Claudio, E; Cunningham, K; Siebenlist, U

2000-09-12

Pathogens, inflammatory signals, and stress cause acute transcriptional responses in cells. The induced expression of genes in response to these signals invariably involves transcription factors of the NF-kappaB and AP-1/ATF families. Activation of NF-kappaB factors is thought to be mediated primarily via IkappaB kinases (IKK), whereas that of AP-1/ATF can be mediated by stress-activated protein kinases (SAPKs; also named Jun kinases or JNKs). IKKalpha and IKKbeta are two catalytic subunits of a core IKK complex that also contains the regulatory subunit NEMO (NF-kappaB essential modulator)/IKKgamma. The latter protein is essential for activation of the IKKs, but its mechanism of action is not known. Here we describe the molecular cloning of CIKS (connection to IKK and SAPK/JNK), a previously unknown protein that directly interacts with NEMO/IKKgamma in cells. When ectopically expressed, CIKS stimulates IKK and SAPK/JNK kinases and it transactivates an NF-kappaB-dependent reporter. Activation of NF-kappaB is prevented in the presence of kinase-deficient, interfering mutants of the IKKs. CIKS may help to connect upstream signaling events to IKK and SAPK/JNK modules. CIKS could coordinate the activation of two stress-induced signaling pathways, functions reminiscent of those noted for tumor necrosis factor receptor-associated factor adaptor proteins.

Interactions between the cytomegalovirus promoter and the estrogen response element: implications for design of estrogen-responsive reporter plasmids.

PubMed

Derecka, K; Wang, C K; Flint, A P F

2006-07-01

We aimed to produce an estrogen-responsive reporter plasmid that would permit monitoring of estrogen receptor function in the uterus in vivo. The plasmid pBL-tk-CAT(+)ERE was induced by estrogen in bovine endometrial stromal cells. When the CAT gene was replaced by the secreted alkaline phosphatase SeAP, the resulting construct pBL-tk-SeAP(+)ERE remained estrogen responsive. However when the tk promoter was replaced by the cytomegalovirus (cmv) promoter, the resulting plasmid (pBL-cmv-SeAP(+)ERE) was not estrogen responsive. Inhibition of ERE function was not due to an effect in trans or due to lack of estrogen receptor. It was not due to an interaction between the cmv promoter and the SeAP gene. cmv promoter function was dependent on NF-kappaB, and mutagenesis in the NF-kappaB sites reduced basal reporter expression without imparting responsiveness to estrogen. A mutation in the TATA box also failed to impart estrogen responsiveness. Modeling of DNA accessibility indicated the ERE was inserted at a site accessible to transcription factors. We conclude that the cmv promoter inhibits ERE function in cis when the two sequences are located in the same construct, and that this effect does not involve an interaction between cmv and reporter gene, NF-kappaB sites or the TATA box, or DNA inaccessibility.

Role of adapter function in oncoprotein-mediated activation of NF-kappaB. Human T-cell leukemia virus type I Tax interacts directly with IkappaB kinase gamma.

PubMed

Jin, D Y; Giordano, V; Kibler, K V; Nakano, H; Jeang, K T

1999-06-18

Mechanisms by which the human T-cell leukemia virus type I Tax oncoprotein activates NF-kappaB remain incompletely understood. Although others have described an interaction between Tax and a holo-IkappaB kinase (IKK) complex, the exact details of protein-protein contact are not fully defined. Here we show that Tax binds to neither IKK-alpha nor IKK-beta but instead complexes directly with IKK-gamma, a newly characterized component of the IKK complex. This direct interaction with IKK-gamma correlates with Tax-induced IkappaB-alpha phosphorylation and NF-kappaB activation. Thus, our findings establish IKK-gamma as a key molecule for adapting an oncoprotein-specific signaling to IKK-alpha and IKK-beta.

Generation and analysis of the improved human HAL9/10 antibody phage display libraries.

PubMed

Kügler, Jonas; Wilke, Sonja; Meier, Doris; Tomszak, Florian; Frenzel, André; Schirrmann, Thomas; Dübel, Stefan; Garritsen, Henk; Hock, Björn; Toleikis, Lars; Schütte, Mark; Hust, Michael

2015-02-19

Antibody phage display is a proven key technology that allows the generation of human antibodies for diagnostics and therapy. From naive antibody gene libraries - in theory - antibodies against any target can be selected. Here we describe the design, construction and characterization of an optimized antibody phage display library. The naive antibody gene libraries HAL9 and HAL10, with a combined theoretical diversity of 1.5×10(10) independent clones, were constructed from 98 healthy donors using improved phage display vectors. In detail, most common phagemids employed for antibody phage display are using a combined His/Myc tag for detection and purification. We show that changing the tag order to Myc/His improved the production of soluble antibodies, but did not affect antibody phage display. For several published antibody libraries, the selected number of kappa scFvs were lower compared to lambda scFvs, probably due to a lower kappa scFv or Fab expression rate. Deletion of a phenylalanine at the end of the CL linker sequence in our new phagemid design increased scFv production rate and frequency of selected kappa antibodies significantly. The HAL libraries and 834 antibodies selected against 121 targets were analyzed regarding the used germline V-genes, used V-gene combinations and CDR-H3/-L3 length and composition. The amino acid diversity and distribution in the CDR-H3 of the initial library was retrieved in the CDR-H3 of selected antibodies showing that all CDR-H3 amino acids occurring in the human antibody repertoire can be functionally used and is not biased by E. coli expression or phage selection. Further, the data underline the importance of CDR length variations. The highly diverse universal antibody gene libraries HAL9/10 were constructed using an optimized scFv phagemid vector design. Analysis of selected antibodies revealed that the complete amino acid diversity in the CDR-H3 was also found in selected scFvs showing the functionality of the naive CDR-H3 diversity.

Mapping of cortical language function by functional magnetic resonance imaging and repetitive navigated transcranial magnetic stimulation in 40 healthy subjects.

PubMed

Sollmann, Nico; Ille, Sebastian; Boeckh-Behrens, Tobias; Ringel, Florian; Meyer, Bernhard; Krieg, Sandro M

2016-07-01

Functional magnetic resonance imaging (fMRI) is considered to be the standard method regarding non-invasive language mapping. However, repetitive navigated transcranial magnetic stimulation (rTMS) gains increasing importance with respect to that purpose. However, comparisons between both methods are sparse. We performed fMRI and rTMS language mapping of the left hemisphere in 40 healthy, right-handed subjects in combination with the tasks that are most commonly used in the neurosurgical context (fMRI: word-generation = WGEN task; rTMS: object-naming = ON task). Different rTMS error rate thresholds (ERTs) were calculated, and Cohen's kappa coefficient and the cortical parcellation system (CPS) were used for systematic comparison of the two techniques. Overall, mean kappa coefficients were low, revealing no distinct agreement. We found the highest agreement for both techniques when using the 2-out-of-3 rule (CPS region defined as language positive in terms of rTMS if at least 2 out of 3 stimulations led to a naming error). However, kappa for this threshold was only 0.24 (kappa of <0, 0.01-0.20, 0.21-0.40, 0.41-0.60, 0.61-0.80 and 0.81-0.99 indicate less than chance, slight, fair, moderate, substantial and almost perfect agreement, respectively). Because of the inherent differences in the underlying physiology of fMRI and rTMS, the different tasks used and the impossibility of verifying the results via direct cortical stimulation (DCS) in the population of healthy volunteers, one must exercise caution in drawing conclusions about the relative usefulness of each technique for language mapping. Nevertheless, this study yields valuable insights into these two mapping techniques for the most common language tasks currently used in neurosurgical practice.

Insulin-like growth factor-binding protein-5 (IGFBP-5) inhibits TNF-{alpha}-induced NF-{kappa}B activity by binding to TNFR1

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

Hwang, Jae Ryoung; Huh, Jae Ho; Lee, Yoonna

2011-02-25

Research highlights: {yields} Binding assays demonstrated that secreted- and cellular-IGFBP-5 interacted with TNFR1. {yields} The interaction between IGFBP-5 and TNFR1 was inhibited by TNF-{alpha} and was blocked TNF-{alpha}-activated NF-{kappa}B activity. {yields} IGFBP-5 interacted with TNFR1 through its N- and L-domains but the binding of L-domain to TNFR1 was blocked by TNF-{alpha}. {yields} Competition between the L-domain of IGFBP-5 and TNF-{alpha} blocked TNF-{alpha}-induced NF-{kappa}B activity. {yields} This study suggests that the L-domain of IGFBP-5 is a novel TNFR1 ligand that functions as a competitive TNF-{alpha} inhibitor. -- Abstract: IGFBP-5 is known to be involved in various cell phenomena such as proliferation,more » differentiation, and apoptosis. However, the exact mechanisms by which IGFBP-5 exerts its functions are unclear. In this study, we demonstrate for the first time that IGFBP-5 is a TNFR1-interacting protein. We found that ectopic expression of IGFBP-5 induced TNFR1 gene expression, and that IGFBP-5 interacted with TNFR1 in both an in vivo and an in vitro system. Secreted IGFBP-5 interacted with GST-TNFR1 and this interaction was blocked by TNF-{alpha}, demonstrating that IGFBP-5 might be a TNFR1 ligand. Furthermore, conditioned media containing secreted IGFBP-5 inhibited PMA-induced NF-{kappa}B activity and IL-6 expression in U-937 cells. Coimmunoprecipitation assays of TNFR1 and IGFBP-5 wild-type and truncation mutants revealed that IGFBP-5 interacts with TNFR1 through its N- and L-domains. However, only the interaction between the L-domain of IGFBP-5 and TNFR1 was blocked by TNF-{alpha} in a dose-dependent manner, suggesting that the L-domain of IGFBP-5 can function as a TNFR1 ligand. Competition between the L-domain of IGFBP-5 and TNF-{alpha} resulted in inhibition of TNF-{alpha}-induced NF-{kappa}{Beta} activity. Taken together, our results suggest that the L-domain of IGFBP-5 is a novel TNFR1 ligand that functions as a competitive TNF-{alpha} inhibitor.« less

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.

Nuclear translocation and DNA-binding activity of NFKB (NF-kappaB) after exposure of human monocytes to pulsed ultra-wideband electromagnetic fields (1 kV/cm) fails to transactivate kappaB-dependent gene expression.

PubMed

Natarajan, M; Nayak, B K; Galindo, C; Mathur, S P; Roldan, F N; Meltz, M L

2006-06-01

The objective of this study was to investigate whether exposure of human monocytes to a pulsed ultra-wideband electromagnetic field (EMF) of 1 kV/cm average peak power triggers a signaling pathway responsible for the transcriptional regulation of NFKB (NF-kappaB)-dependent gene expression. Human Mono Mac 6 (MM6) cells were exposed intermittently to EMF pulses for a total of 90 min. The pulse width was 0.79+/-0.01 ns and the pulse repetition rate was 250 pps. The temperature of the medium was maintained at 37 degrees C in both sham- and EMF-exposed flasks. Total NFKB DNA-binding activity was measured in the nuclear extracts by the electrophoretic mobility shift assay. Cells exposed to the EMFs and incubated for 24 h postexposure showed a 3.5+/-0.2-fold increase in the NFKB DNA-binding activity. Since activation of NFKB was observed, the possibility of kappaB-dependent gene expression in response to exposure to the EMFs was investigated using NFKB signal-specific gene arrays. The results revealed no difference in the NFKB-dependent gene expression profiles at 8 or 24 h postexposure, indicating that activated NFKB does not lead to the differential expression of kappaB-dependent target genes. To determine whether the absence of the kappaB-dependent gene expression was due to compromised transcriptional regulation of NFKB, the functional activity of NFKB was examined in cells transiently transfected with Mercury Pathway constructs containing 4x NFKB binding sites associated either with the luciferase reporter system or a control vector. Pulsed EMF exposure did not induce NFKB-driven luciferase activity in these cells, indicating that the activation of NFKB at 24 h after the 1 kV/cm EMF exposure is functionally inactive. From these results, it is clear that the EMF-induced NFKB activation is only a transient response, with minimal or no downstream effect.

Principal component similarity analysis of Raman spectra to study the effects of pH, heating, and kappa-carrageenan on whey protein structure.

PubMed

Alizadeh-Pasdar, Nooshin; Nakai, Shuryo; Li-Chan, Eunice C Y

2002-10-09

Raman spectroscopy was used to elucidate structural changes of beta-lactoglobulin (BLG), whey protein isolate (WPI), and bovine serum albumin (BSA), at 15% concentration, as a function of pH (5.0, 7.0, and 9.0), heating (80 degrees C, 30 min), and presence of 0.24% kappa-carrageenan. Three data-processing techniques were used to assist in identifying significant changes in Raman spectral data. Analysis of variance showed that of 12 characteristics examined in the Raman spectra, only a few were significantly affected by pH, heating, kappa-carrageenan, and their interactions. These included amide I (1658 cm(-1)) for WPI and BLG, alpha-helix for BLG and BSA, beta-sheet for BSA, CH stretching (2880 cm(-1)) for BLG and BSA, and CH stretching (2930 cm(-1)) for BSA. Principal component analysis reduced dimensionality of the characteristics. Heating and its interaction with kappa-carrageenan were identified as the most influential in overall structure of the whey proteins, using principal component similarity analysis.

Extremely Nonthermal Monoenergetic Precipitation in the Auroral Acceleration Region: In Situ Observations

NASA Astrophysics Data System (ADS)

Hatch, S.; Chaston, C. C.; Labelle, J. W.

2017-12-01

We report in situ measurements through the auroral acceleration region that reveal extremely nonthermal monoenergetic electron distributions. These auroral primaries are indicative of source populations in the plasma sheet well described as kappa distributions with κ ≲ 2. We show from observations and modeling how this large deviation from Maxwellian form may modify the acceleration potential required to drive current closure through the auroral ionosphere.

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.

Interplanetary Radiation and Internal Charging Environment Models for Solar Sails

NASA Technical Reports Server (NTRS)

Minow, Joseph I.; Altstatt, Richard L.; Neergaard, Linda F.

2004-01-01

A Solar Sail Radiation Environment (SSRE) model has been developed for characterizing the radiation dose and internal charging environments in the solar wind. The SSRE model defines the 0.01 keV to 1 MeV charged particle environment for use in testing the radiation dose vulnerability of candidate solar sail materials and for use in evaluating the internal charging effects in the interplanetary environment. Solar wind and energetic particle instruments aboard the Ulysses spacecraft provide the particle data used to derive the environments for the high inclination 0.5 AU Solar Polar Imager mission and the 1.0 AU L1 solar sail missions. Ulysses is the only spacecraft to sample high latitude solar wind environments far from the ecliptic plane and is therefore uniquely capable of providing the information necessary for defining radiation environments for the Solar Polar Imager spacecraft. Cold plasma moments are used to derive differential flux spectra based on Kappa distribution functions. Energetic particle flux measurements are used to constrain the high energy, non-thermal tails of the distribution functions providing a comprehensive electron, proton, and helium spectra from less than 0.01 keV to a few MeV.

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.

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.

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 electroacoustic theory is valid for almost all nonaqueous dispersions and a wide variety of nanocolloids, especially with sizes under 100 nm.

TNF-alpha increases ubiquitin-conjugating activity in skeletal muscle by up-regulating UbcH2/E220k

NASA Technical Reports Server (NTRS)

Li, Yi-Ping; Lecker, Stewart H.; Chen, Yuling; Waddell, Ian D.; Goldberg, Alfred L.; Reid, Michael B.

2003-01-01

In some inflammatory diseases, TNF-alpha is thought to stimulate muscle catabolism via an NF-kappaB-dependent process that increases ubiquitin conjugation to muscle proteins. The transcriptional mechanism of this response has not been determined. Here we studied the potential role of UbcH2, a ubiquitin carrier protein and homologue of murine E220k. We find that UbcH2 is constitutively expressed by human skeletal and cardiac muscles, murine limb muscle, and cultured myotubes. TNF-alpha stimulates UbcH2 expression in mouse limb muscles in vivo and in cultured myotubes. The UbcH2 promoter region contains a functional NF-kappaB binding site; NF-kappaB binding to this sequence is increased by TNF-alpha stimulation. A dominant negative inhibitor of NF-kappaB activation blocks both UbcH2 up-regulation and the increase in ubiquitin-conjugating activity stimulated by TNF-alpha. In extracts from TNF-alpha-treated myotubes, ubiquitin-conjugating activity is limited by UbcH2 availability; activity is inhibited by an antiserum to UbcH2 or a dominant negative mutant of UbcH2 and is enhanced by wild-type UbcH2. Thus, UbcH2 up-regulation is a novel response to TNF-alpha/NF-kappaB signaling in skeletal muscle that appears to be essential for the increased ubiquitin conjugation induced by this cytokine.

Withaferin A inhibits tumor necrosis factor-alpha-induced expression of cell adhesion molecules by inactivation of Akt and NF-kappaB in human pulmonary epithelial cells.

PubMed

Oh, Jung Hwa; Kwon, Taeg Kyu

2009-05-01

We here investigated the functional effect of withaferin A on airway inflammation and its action mechanism. Withaferin A inhibited the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in human lung epithelial A549 cells stimulated with tumor necrosis factor-alpha (TNF-alpha), resulting in the suppression of leukocyte adhesion to lung epithelial A549 cells. In addition, withaferin A inhibited TNF-alpha-induced expression of adhesion molecules (ICAM-1 and VCAM-1) protein and mRNA in a dose-dependent manner. Withaferin A prevented DNA binding activity of nuclear factor-kappaB (NF-kappaB) and nuclear translocation of NF-kappaB. It also inhibited phosphorylation of Akt and extracellular signal-regulated kinase (ERK), which are upstream in the regulation of adhesion molecules by TNF-alpha. Furthermore, withaferin A inhibited U937 monocyte adhesion to A549 cells stimulated by TNF-alpha, suggesting that it may inhibit the binding of these cells by regulating the expression of critical adhesion molecules by TNF-alpha. Taken together, these results suggest that withaferin A inhibits cell adhesion through inhibition of ICAM-1 and VCAM-1 expression, at least in part, by blocking Akt and down-regulating NF-kappaB activity.

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.

Citizen Science and Open Data: a Model for Invasive Alien Plant Species in Kenya's Northern Rangelands

NASA Astrophysics Data System (ADS)

Amirazodi, S.; Griffin, R.; Flores Cordova, A. I.; Ouko, E.; Omondi, S.; Mugo, R. M.; Farah, H.; Flores Cordova, A. I.; Adams, E. C.

2017-12-01

Invasive species in African savannas pose great threat to the native biodiversity and changes ecosystem functioning. In the forest sector, for instance Acacia species are important sources of fuel-wood, yet at the same time they have increased strain on water resources and shrunken forage spaces for both livestock and wildlife. In recently infested regions, invasive species can progress through the stages of introduction, establishment and dispersal to a full range. Currently there is much worldwide interest in predicting distributions of invasive species, and several organizations are faced with questions of whether and how to tackle such environmental challenges, or how to interpret predictions from the science community. Conservation practioners require mapped estimates of where species could persist in a given region, and this is associated to information about the biotope - i.e. the geographic location of the species' niche. The process of collecting species distribution data for identifying the potential distribution of the invasive species in the invaded ranges has become a challenge both in terms of resource and time allocation. This study highlights innovative approaches in crowdsourcing validation data in mapping and modelling invasive species (Acacia reficiens and Cactus) through involvement of the local communities. The general approach was to model the distribution of A. reficiens and Cactus (Opuntia Spp) using occurrence records from native range, then project the model into new regions to assess susceptibility to invasion using climatic and topographic environmental variables. The models performed better than random prediction (P < 0.05). The average testing omission rate varied from 11.3% to 14% for the two species. The average test AUC values for Acacia reficiens (0.97 ± 0.01) and Cactus (Opuntia Spp) (0.96 ± 0.02) were high showing the fitted models had high discriminative ability to differentiate suitable environments for invasive plant species from random background points. Precipitation of the driest month & vegetation indices were most important variables. Results from Kappa tests revealed generally good model (s) performance, with all the two species achieving Kappa scores > 0.75.

Coulomb Scattering in the Massless Nelson Model III: Ground State Wave Functions and Non-commutative Recurrence Relations

NASA Astrophysics Data System (ADS)

Dybalski, Wojciech; Pizzo, Alessandro

2018-02-01

Let $H_{P,\\sigma}$ be the single-electron fiber Hamiltonians of the massless Nelson model at total momentum $P$ and infrared cut-off $\\sigma>0$. We establish detailed regularity properties of the corresponding $n$-particle ground state wave functions $f^n_{P,\\sigma}$ as functions of $P$ and $\\sigma$. In particular, we show that \\[ |\\partial_{P^j}f^{n}_{P,\\sigma}(k_1,\\ldots, k_n)|, \\ \\ |\\partial_{P^j} \\partial_{P^{j'}} f^{n}_{P,\\sigma}(k_1,\\ldots, k_n)| \\leq \\frac{1}{\\sqrt{n!}} \\frac{(c\\lambda_0)^n}{\\sigma^{\\delta_{\\lambda_0}}} \\prod_{i=1}^n\\frac{ \\chi_{[\\sigma,\\kappa)}(k_i)}{|k_i|^{3/2}}, \\] where $c$ is a numerical constant, $\\lambda_0\\mapsto \\delta_{\\lambda_0}$ is a positive function of the maximal admissible coupling constant which satisfies $\\lim_{\\lambda_0\\to 0}\\delta_{\\lambda_0}=0$ and $\\chi_{[\\sigma,\\kappa)}$ is the (approximate) characteristic function of the energy region between the infrared cut-off $\\sigma$ and the ultraviolet cut-off $\\kappa$. While the analysis of the first derivative is relatively straightforward, the second derivative requires a new strategy. By solving a non-commutative recurrence relation we derive a novel formula for $f^n_{P,\\sigma}$ with improved infrared properties. In this representation $\\partial_{P^{j'}}\\partial_{P^{j}}f^n_{P,\\sigma}$ is amenable to sharp estimates obtained by iterative analytic perturbation theory in part II of this series of papers. The bounds stated above are instrumental for scattering theory of two electrons in the Nelson model, as explained in part I of this series.

Prediction of cloud condensation nuclei activity for organic compounds using functional group contribution methods

DOE PAGES

Petters, M. D.; Kreidenweis, S. M.; Ziemann, P. J.

2016-01-19

A wealth of recent laboratory and field experiments demonstrate that organic aerosol composition evolves with time in the atmosphere, leading to changes in the influence of the organic fraction to cloud condensation nuclei (CCN) spectra. There is a need for tools that can realistically represent the evolution of CCN activity to better predict indirect effects of organic aerosol on clouds and climate. This work describes a model to predict the CCN activity of organic compounds from functional group composition. Following previous methods in the literature, we test the ability of semi-empirical group contribution methods in Kohler theory to predict themore » effective hygroscopicity parameter, kappa. However, in our approach we also account for liquid–liquid phase boundaries to simulate phase-limited activation behavior. Model evaluation against a selected database of published laboratory measurements demonstrates that kappa can be predicted within a factor of 2. Simulation of homologous series is used to identify the relative effectiveness of different functional groups in increasing the CCN activity of weakly functionalized organic compounds. Hydroxyl, carboxyl, aldehyde, hydroperoxide, carbonyl, and ether moieties promote CCN activity while methylene and nitrate moieties inhibit CCN activity. Furthermore, the model can be incorporated into scale-bridging test beds such as the Generator of Explicit Chemistry and Kinetics of Organics in the Atmosphere (GECKO-A) to evaluate the evolution of kappa for a complex mix of organic compounds and to develop suitable parameterizations of CCN evolution for larger-scale models.« less

Half molecular exchange of IgGs in the blood of healthy humans: chimeric lambda-kappa-immunoglobulins containing HL fragments of antibodies of different subclasses (IgG1-IgG4).

PubMed

Sedykh, Sergey E; Lekchnov, Evgenii A; Prince, Viktor V; Buneva, Valentina N; Nevinsky, Georgy A

2016-10-20

In the classic paradigm, immunoglobulins represent products of clonal B cell populations, each producing antibodies recognizing a single antigen (monospecific). There is a common belief that IgGs in mammalian biological fluids are monospecific molecules having stable structures and two identical antigen-binding sites. But the issue concerning the possibility of exchange by HL-fragments between the antibody molecules in human blood is still unexplored. Different physico-chemical and immunological methods for analysis of half-molecule exchange between human blood IgGs were used. Using eighteen blood samples of healthy humans we have shown unexpected results for the first time: blood antibodies undergo extensive post-transcriptional half-molecule exchange and IgG pools on average consist of 62.4 ± 6.5% IgGs containing kappa light chains (kappa-kappa-IgGs), 29.8.6 ± 5.4% lambda light chains (lambda-lambda-IgGs), and 8.8 ± 2.7% (range 2.6-16.8%) IgGs containing both kappa- and lambda-light chains. Kappa-kappa-IgGs and lambda-lambda-IgGs contained on average (%): IgG1 (36.0 and 32.3), IgG2 (50.9 and 51.4), IgG3 (9.7 and 9.9), and IgG4 (6.5 and 5.7), while chimeric kappa-lambda-IgGs consisted of (%): 25.5 ± 4.2 IgG1, 50.8 ± 3.9 IgG2, 9.1 ± 2.1 IgG3, and 14.5 ± 2.2 IgG4. Our unexpected data are indicative of the possibility of half-molecule exchange between blood IgGs of various subclasses, raised against different antigens. The existence of blood chimeric bifunctional IgGs with different binding sites destroys the classic paradigm. Due to the phenomenon of polyspecificity and cross-reactivity of bifunctional IgGs containing HL-fragments of different types to different antigens, such IgGs may be important in human blood for widening their different biological functions.

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.

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

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.

Anti-inflammatory activity of 4-methoxyhonokiol is a function of the inhibition of iNOS and COX-2 expression in RAW 264.7 macrophages via NF-kappaB, JNK and p38 MAPK inactivation.

PubMed

Zhou, Hong Yu; Shin, Eun Myoung; Guo, Lian Yu; Youn, Ui Joung; Bae, KiHwan; Kang, Sam Sik; Zou, Li Bo; Kim, Yeong Shik

2008-05-31

The extracts or constituents from the bark of Magnolia (M.) obovata are known to have many pharmacological activities. 4-Methoxyhonokiol, a neolignan compound isolated from the stem bark of M. obovata, was found to exhibit a potent anti-inflammatory effect in different experimental models. Pretreatment with 4-methoxyhonokiol (i.p.) dose-dependently inhibited the dye leakage and paw swelling in an acetic-acid-induced vascular permeability assay and a carrageenan-induced paw edema assay in mice, respectively. In the lipopolysaccharide (LPS)-induced systemic inflammation model, 4-methoxyhonokiol significantly inhibited plasma nitric oxide (NO) release in mice. To identify the mechanisms underlying this anti-inflammatory action, we investigated the effect of 4-methoxyhonokiol on LPS-induced responses in a murine macrophage cell line, RAW 264.7. The results demonstrated that 4-methoxyhonokiol significantly inhibited LPS-induced NO production as well as the protein and mRNA expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, 4-methoxyhonokiol inhibited LPS-mediated nuclear factor-kappaB (NF-kappaB) activation via the prevention of inhibitor kappaB (IkappaB) phosphorylation and degradation. 4-Methoxyhonokiol had no effect on the LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK), whereas it attenuated the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun NH2-terminal kinase (JNK) in a concentration-dependent manner. Taken together, our data suggest that 4-methoxyhonokiol is an active anti-inflammatory constituent of the bark of M. obovata, and that its anti-inflammatory property might be a function of the inhibition of iNOS and COX-2 expression via down-regulation of the JNK and p38 MAP kinase signal pathways and inhibition of NF-kappaB activation in RAW 264.7 macrophages.

Dementia diagnoses from clinical and neuropsychological data compared: the Cache County study.

PubMed

Tschanz, J T; Welsh-Bohmer, K A; Skoog, I; West, N; Norton, M C; Wyse, B W; Nickles, R; Breitner, J C

2000-03-28

To validate a neuropsychological algorithm for dementia diagnosis. We developed a neuropsychological algorithm in a sample of 1,023 elderly residents of Cache County, UT. We compared algorithmic and clinical dementia diagnoses both based on DSM-III-R criteria. The algorithm diagnosed dementia when there was impairment in memory and at least one other cognitive domain. We also tested a variant of the algorithm that incorporated functional measures that were based on structured informant reports. Of 1,023 participants, 87% could be classified by the basic algorithm, 94% when functional measures were considered. There was good concordance between basic psychometric and clinical diagnoses (79% agreement, kappa = 0.57). This improved after incorporating functional measures (90% agreement, kappa = 0.76). Neuropsychological algorithms may reasonably classify individuals on dementia status across a range of severity levels and ages and may provide a useful adjunct to clinical diagnoses in population studies.

Anti-inflammatory function of Withangulatin A by targeted inhibiting COX-2 expression via MAPK and NF-kappaB pathways.

PubMed

Sun, Lijuan; Liu, Jianwen; Cui, Daling; Li, Jiyu; Yu, Youjun; Ma, Lei; Hu, Lihong

2010-02-15

Withangulatin A (WA), an active component isolated from Physalis angulata L., has been reported to possess anti-tumor and trypanocidal activities in model systems via multiple biochemical mechanisms. The aim of this study is to investigate its anti-inflammatory potential and the possible underlying mechanisms. In the current study, WA significantly suppressed mice T lymphocytes proliferation stimulated with LPS in a dose- and time-dependent manner and inhibited pro-inflammation cytokines (IL-2, IFN-gamma, and IL-6) dramatically. Moreover, WA targeted inhibited COX-2 expression mediated by MAPKs and NF-kappaB nuclear translocation pathways in mice T lymphocytes, and this result was further confirmed by the COX-1/2 luciferase reporter assay. Intriguingly, administration of WA inhibited the extent of mice ear swelling and decreased pro-inflammatory cytokines production in mice blood serum. Based on these evidences, WA influences the mice T lymphocytes function through targeted inhibiting COX-2 expression via MAPKs and NF-kappaB nuclear translocation signaling pathways, and this would make WA a strong candidate for further study as an anti-inflammatory agent. (c) 2009 Wiley-Liss, Inc.

The validity and reliability of a simple semantic classification of foot posture.

PubMed

Cross, Hugh A; Lehman, Linda

2008-12-01

The Simple Semantic Classification (SSC) is described as a pragmatic method to assist in the assessment of the weight bearing foot. It was designed for application by therapists and technicians working in underdeveloped situations, after they have had basic orientation in foot function. To present evidence of the validity and inter observer reliability of the SSC. 13 physiotherapists from LEPRA India projects and 12 physical therapists functioning within the National Programme for the Elimination of Hansen's Disease (PNEH), Brazil, participated in an inter-observer exercise. Inter-observer agreement was gauged using the Kappa statistic. The results of the inter-observer exercise were dependent on observations of foot posture made from photographs. This was necessary to ensure that the procedure was standardised for participants in different countries. The method had limitations which were partly reflected in the results. The level of agreement between the principle investigator and Indian physiotherapists was Kappa = 058. The level of agreement between Brazilian physical therapists and the principle investigator was Kappa = 0.70. The authors opine that the results were sufficiently compelling to suggest that the Simple Semantic Classification can be used as a field method to identify people at increased risk of foot pathologies.

Curriculum Theory and Practice: What's Your Style?

ERIC Educational Resources Information Center

Miller, Donna L.

2011-01-01

Four common schools of thought in the curriculum arena are the linear, holistic, laissez faire, and critical theorist approaches. When teachers identify which approach they are most apt to use, they can consciously incorporate other styles into their practice. The author holds copyright to this article. Distributed by Phi Delta Kappa with…

[Development and reliability evaluation of an instrument to measure health-related quality of life in independent elderly].

PubMed

Lima, Maria José Barbosa de; Portela, Margareth Crisóstomo

2010-08-01

This study presents an instrument, the health-related quality of life (HRQOL) profile for independent elderly, to measure the health-related quality of life of the functionally independent elderly assisted in the outpatient setting, based on the adaptation of four validated scales: Short-Form Health Survey (SF-36), Duke-UNC Health Profile (DUHP), Sickness Impact Profile (SIP), and Nottingham Health Profile (NHP). The study also evaluates the instrument's reliability based on its use by two different observers with a 15-day interval. The instrument includes five dimensions (health perception, symptoms, physical function, psychological function, and social function) and 45 items. Reliability evaluation of the QUASI instrument was based on interviews with 142 elderly outpatients in the city of Rio de Janeiro, Brazil. Prevalence-adjusted kappa statistic was used to assess all 45 items. Correlation was also calculated between overall scores and scores on individual dimensions. In the reliability evaluation, 39 of the 45 items showed prevalence-adjusted kappa greater than 0.60.

Breakdown of Universality for Unequal-Mass Fermi Gases with Infinite Scattering Length

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

Blume, D.; Daily, K. M.

We treat small trapped unequal-mass two-component Fermi gases at unitarity within a nonperturbative microscopic framework and investigate the system properties as functions of the mass ratio {kappa}, and the numbers N{sub 1} and N{sub 2} of heavy and light fermions. While equal-mass Fermi gases with infinitely large interspecies s-wave scattering length a{sub s} are universal, we find that unequal-mass Fermi gases are, for sufficiently large {kappa} and in the regime where Efimov physics is absent, not universal. In particular, the (N{sub 1},N{sub 2})=(2,1) and (3, 1) systems exhibit three-body and four-body resonances at {kappa}=12.314(2) and 10.4(2), respectively, as well asmore » surprisingly large finite-range effects. These findings have profound implications for ongoing experimental efforts and quantum simulation proposals that utilize unequal-mass atomic Fermi gases.« less

Assessment of hypoxia and TNF-alpha response by a vector with HRE and NF-kappaB response elements.

PubMed

Chen, Zhilin; Eadie, Ashley L; Hall, Sean R; Ballantyne, Laurel; Ademidun, David; Tse, M Yat; Pang, Stephen C; Melo, Luis G; Ward, Christopher A; Brunt, Keith R

2017-01-01

Hypoxia and inflammatory cytokine activation (H&I) are common processes in many acute and chronic diseases. Thus, a single vector that responds to both hypoxia and inflammatory cytokines, such as TNF-alpha, is useful for assesing the severity of such diseases. Adaptation to hypoxia is regulated primarily by hypoxia inducible transcription factor (HIF alpha) nuclear proteins that engage genes containing a hypoxia response element (HRE). Inflammation activates a multitude of cytokines, including TNF-alpha, that invariably modulate activation of the nuclear factor kappa B (NF-kB) transcription factor. We constructed a vector that encompassed both a hypoxia response element (HRE), and a NF-kappaB responsive element. We show that this vector was functionally responsive to both hypoxia and TNF-alpha, in vitro and in vivo . Thus, this vector might be suitable for the detection and assessment of hypoxia or TNF-alpha.

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.

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

Lin, R.-W.; Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan; Chen, C.-H.

People who regularly drink tea have been found to have a higher bone mineral density (BMD) and to be at less risk of hip fractures than those who do not drink it. Green tea catechins such as (-)-epigallocatechin gallate (EGCG) have been reported to increase osteogenic functioning in mesenchymal stem cells. However, its effect on osteoclastogenesis remains unclear. In this study, we investigated the effect of EGCG on RANKL-activation osteoclastogenesis and NF-{kappa}B in RAW 264.7, a murine preosteoclast cell line. EGCG (10-100 {mu}M) significantly suppressed the RANKL-induced differentiation of osteoclasts and the formation of pits in murine RAW 264.7 cellsmore » and bone marrow macrophages (BMMs). EGCG appeared to target osteoclastic differentiation at an early stage but had no cytotoxic effect on osteoclast precursors. In addition, it significantly inhibited RANKL-induced NF-{kappa}B transcriptional activity and nuclear translocation. We conclude that EGCG inhibits osteoclastogenesis through its activation of NF-{kappa}B.« less

Opioid hedonic hotspot in nucleus accumbens shell: mu, delta, and kappa maps for enhancement of sweetness "liking" and "wanting".

PubMed

Castro, Daniel C; Berridge, Kent C

2014-03-19

A specialized cubic-millimeter hotspot in the rostrodorsal quadrant of medial shell in nucleus accumbens (NAc) of rats may mediate opioid enhancement of gustatory hedonic impact or "liking". Here, we selectively stimulated the three major subtypes of opioid receptors via agonist microinjections [mu (DAMGO), delta (DPDPE), or kappa (U50488H)] and constructed anatomical maps for functional localizations of consequent changes in hedonic "liking" (assessed by affective orofacial reactions to sucrose taste) versus "wanting" (assessed by changes in food intake). Results indicated that the NAc rostrodorsal quadrant contains a shared opioid hedonic hotspot that similarly mediates enhancements of sucrose "liking" for mu, delta, and kappa stimulations. Within the rostrodorsal hotspot boundaries each type of stimulation generated at least a doubling or higher enhancement of hedonic reactions, with comparable intensities for all three types of opioid stimulation. By contrast, a negative hedonic coldspot was mapped in the caudal half of medial shell, where all three types of opioid stimulation suppressed "liking" reactions to approximately one-half normal levels. Different anatomical patterns were produced for stimulation of food "wanting", reflected in food intake. Altogether, these results indicate that the rostrodorsal hotspot in medial shell is unique for generating opioid-induced hedonic enhancement, and add delta and kappa signals to mu as hedonic generators within the hotspot. Also, the identification of a separable NAc caudal coldspot for hedonic suppression, and separate NAc opioid mechanisms for controlling food "liking" versus "wanting" further highlights NAc anatomical heterogeneity and localizations of function within subregions of medial shell.

Anti-inflammatory and antitumor promotional effects of a novel urinary metabolite, 3',4'-didemethylnobiletin, derived from nobiletin.

PubMed

Lai, Ching-Shu; Li, Shiming; Chai, Chee-Yin; Lo, Chih-Yu; Dushenkov, Slavik; Ho, Chi-Tang; Pan, Min-Hsiung; Wang, Ying-Jan

2008-12-01

We reported previously that 3',4'-didemethylnobiletin (DDMN) is the major metabolite of nobiletin in mouse urine. In this study, we examined DDMN's molecular mechanism of action and its anti-inflammatory and antitumor properties. We demonstrated that topical application of DDMN effectively inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated transcription of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and ornithine decarboxylase (ODC) messenger RNA and protein expression in mouse skin. Pretreatment with DDMN has resulted in the reduction of TPA-induced nuclear translocation of the nuclear factor-kappa B (NF-kappaB) subunit. DDMN also reduced DNA binding by blocking phosphorylation of inhibitor kappaB (IkappaB) alpha and p65 and caused subsequent degradation of IkappaBalpha. DDMN inhibited TPA-induced phosphorylation and nuclear translocation of the signal transducer and activator of transcription 3. Moreover, DDMN suppressed TPA-induced activation of extracellular signal-regulated kinase 1/2, p38 mitogen-activated protein kinase, phosphatidylinositol 3-kinase/Akt and protein kinase C that are upstream of NF-kappaB and activator protien-1. We also found that DDMN significantly inhibited TPA-induced mouse skin inflammation by decreasing inflammatory parameters. Furthermore, DDMN significantly inhibited 7,12-dimethylbenz[a]anthracene/TPA-induced skin tumor formation measured by the tumor multiplicity of papillomas at 20 weeks. Presented data for the first time reveal that DDMN is an effective antitumor agent that functions by downregulating inflammatory iNOS, COX-2 and ODC gene expression in mouse skin. It is suggested that DDMN is a novel functional agent capable of preventing inflammation-associated tumorigenesis.

Coupling of Charged Particles Via Coulombic Interactions: Numerical Simulations and Resultant Kappa-Like Velocity Space Distribution Functions

NASA Technical Reports Server (NTRS)

Randol, Brent M.; Christian, Eric R.

2016-01-01

A parametric study is performed using the electrostatic simulations of Randol and Christian (2014) in which the number density, n, and initial thermal speed, theta, are varied. The range of parameters covers an extremely broad plasma regime, all the way from the very weak coupling of space plasmas to the very strong coupling of solid plasmas. The first result is that simulations at the same Lambda(sub D), where Lambda(sub D) is the plasma coupling parameter, but at different combinations of n and theta, behave exactly the same. As a function of Lambda(sub D), the form of p(v), the velocity distribution function of v, the magnitude of v, the velocity vector, is studied. For intermediate to high D, heating is observed in p(v) that obeys conservation of energy, and a suprathermal tail is formed, with a spectral index that depends on Lambda(sub D). For strong coupling (Lambda(sub D) much > 1), the form of the tail is v5, consistent with the findings of Randol and Christian (2014). For weak coupling (Lambda(sub D much <1), no acceleration or heating occurs, as there is no free energy. The dependence on N, the number of particles in the simulation, is also explored. There is a subtle dependence in the index of the tail, such that v5 appears to be the N approaches infinity limit.

Coupling of charged particles via Coulombic interactions: Numerical simulations and resultant kappa-like velocity space distribution functions

NASA Astrophysics Data System (ADS)

Randol, Brent M.; Christian, Eric R.

2016-03-01

A parametric study is performed using the electrostatic simulations of Randol and Christian in which the number density, n, and initial thermal speed, θ, are varied. The range of parameters covers an extremely broad plasma regime, all the way from the very weak coupling of space plasmas to the very strong coupling of solid plasmas. The first result is that simulations at the same ΓD, where ΓD (∝ n1/3θ-2) is the plasma coupling parameter, but at different combinations of n and θ, behave exactly the same. As a function of ΓD, the form of p(v), the velocity distribution function of v, the magnitude of v, the velocity vector, is studied. For intermediate to high ΓD, heating is observed in p(v) that obeys conservation of energy, and a suprathermal tail is formed, with a spectral index that depends on ΓD. For strong coupling (ΓD≫1), the form of the tail is v-5, consistent with the findings of Randol and Christian). For weak coupling (ΓD≪1), no acceleration or heating occurs, as there is no free energy. The dependence on N, the number of particles in the simulation, is also explored. There is a subtle dependence in the index of the tail, such that v-5 appears to be the N→∞ limit.

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

Macrophages of multiple sclerosis patients display deficient SHP-1 expression and enhanced inflammatory phenotype.

PubMed

Christophi, George P; Panos, Michael; Hudson, Chad A; Christophi, Rebecca L; Gruber, Ross C; Mersich, Akos T; Blystone, Scott D; Jubelt, Burk; Massa, Paul T

2009-07-01

Recent studies in mice have demonstrated that the protein tyrosine phosphatase SHP-1 is a crucial negative regulator of proinflammatory cytokine signaling, TLR signaling, and inflammatory gene expression. Furthermore, mice genetically lacking SHP-1 (me/me) display a profound susceptibility to inflammatory CNS demyelination relative to wild-type mice. In particular, SHP-1 deficiency may act predominantly in inflammatory macrophages to increase CNS demyelination as SHP-1-deficient macrophages display coexpression of inflammatory effector molecules and increased demyelinating activity in me/me mice. Recently, we reported that PBMCs of multiple sclerosis (MS) patients have a deficiency in SHP-1 expression relative to normal control subjects indicating that SHP-1 deficiency may play a similar role in MS as to that seen in mice. Therefore, it became essential to examine the specific expression and function of SHP-1 in macrophages from MS patients. Herein, we document that macrophages of MS patients have deficient SHP-1 protein and mRNA expression relative to those of normal control subjects. To examine functional consequences of the lower SHP-1, the activation of STAT6, STAT1, and NF-kappaB was quantified and macrophages of MS patients showed increased activation of these transcription factors. In accordance with this observation, several STAT6-, STAT1-, and NF-kappaB-responsive genes that mediate inflammatory demyelination were increased in macrophages of MS patients following cytokine and TLR agonist stimulation. Supporting a direct role of SHP-1 deficiency in altered macrophage function, experimental depletion of SHP-1 in normal subject macrophages resulted in an increased STAT/NF-kappaB activation and increased inflammatory gene expression to levels seen in macrophages of MS patients. In conclusion, macrophages of MS patients display a deficiency of SHP-1 expression, heightened activation of STAT6, STAT1, and NF-kappaB and a corresponding inflammatory profile that may be important in controlling macrophage-mediated demyelination in MS.

[Validation of National College Health Risk Behavior Survey to be use with Brazilian college students].

PubMed

Franca, Carolina da; Colares, Viviane

2010-06-01

The objective of this article is to translate, to adapt and to validate the National College Health Risk Behavior Survey to apply at Brazilian college students. 208 college students from the Federal University of Pernambuco (UFPE) and University of Pernambuco (UPE) participated in the study. The validation was carried through in five stages: (1) translation; (2) retrotranslation; (3) correction and semantic adaptation (cultural adaptation); (4) face validation; (5) test-retest. Adaptations were done to deal with any semantic disagreements found between translation and retrotranslation. After face validation, the questionnaire was reduced from 96 to 52 questions. From the 11 items analyzed, the majority presented good and perfect Kappa: security and violence (Kappa=0.89); suicide (Kappa=1.00); use of the tobacco (Kappa=0.90); drinking consumption (Kappa=0.78); cocaine and other drugs consumption (Kappa=0.70); sexual behavior (Kappa=0,88) and corporal weight (Kappa=0.89). Only the item about feeding presented weak Inter-examiner Kappa (Kappa = 0.26) and the topic on health information presented moderate Kappa (Kappa=0.56). The average Kappa for all items was good (0.76). The instrument may be considered validated in the Portuguese language in Brazil with acceptable reproducibility.

Kinetic corrections from analytic non-Maxwellian distribution functions in magnetized plasmas

NASA Astrophysics Data System (ADS)

Izacard, Olivier

2016-08-01

In magnetized plasma physics, almost all developed analytic theories assume a Maxwellian distribution function (MDF) and in some cases small deviations are described using the perturbation theory. The deviations with respect to the Maxwellian equilibrium, called kinetic effects, are required to be taken into account especially for fusion reactor plasmas. Generally, because the perturbation theory is not consistent with observed steady-state non-Maxwellians, these kinetic effects are numerically evaluated by very central processing unit (CPU)-expensive codes, avoiding the analytic complexity of velocity phase space integrals. We develop here a new method based on analytic non-Maxwellian distribution functions constructed from non-orthogonal basis sets in order to (i) use as few parameters as possible, (ii) increase the efficiency to model numerical and experimental non-Maxwellians, (iii) help to understand unsolved problems such as diagnostics discrepancies from the physical interpretation of the parameters, and (iv) obtain analytic corrections due to kinetic effects given by a small number of terms and removing the numerical error of the evaluation of velocity phase space integrals. This work does not attempt to derive new physical effects even if it could be possible to discover one from the better understandings of some unsolved problems, but here we focus on the analytic prediction of kinetic corrections from analytic non-Maxwellians. As applications, examples of analytic kinetic corrections are shown for the secondary electron emission, the Langmuir probe characteristic curve, and the entropy. This is done by using three analytic representations of the distribution function: the Kappa distribution function, the bi-modal or a new interpreted non-Maxwellian distribution function (INMDF). The existence of INMDFs is proved by new understandings of the experimental discrepancy of the measured electron temperature between two diagnostics in JET. As main results, it is shown that (i) the empirical formula for the secondary electron emission is not consistent with a MDF due to the presence of super-thermal particles, (ii) the super-thermal particles can replace a diffusion parameter in the Langmuir probe current formula, and (iii) the entropy can explicitly decrease in presence of sources only for the introduced INMDF without violating the second law of thermodynamics. Moreover, the first order entropy of an infinite number of super-thermal tails stays the same as the entropy of a MDF. The latter demystifies the Maxwell's demon by statistically describing non-isolated systems.

Kinetic corrections from analytic non-Maxwellian distribution functions in magnetized plasmas

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

Izacard, Olivier, E-mail: izacard@llnl.gov

In magnetized plasma physics, almost all developed analytic theories assume a Maxwellian distribution function (MDF) and in some cases small deviations are described using the perturbation theory. The deviations with respect to the Maxwellian equilibrium, called kinetic effects, are required to be taken into account especially for fusion reactor plasmas. Generally, because the perturbation theory is not consistent with observed steady-state non-Maxwellians, these kinetic effects are numerically evaluated by very central processing unit (CPU)-expensive codes, avoiding the analytic complexity of velocity phase space integrals. We develop here a new method based on analytic non-Maxwellian distribution functions constructed from non-orthogonal basismore » sets in order to (i) use as few parameters as possible, (ii) increase the efficiency to model numerical and experimental non-Maxwellians, (iii) help to understand unsolved problems such as diagnostics discrepancies from the physical interpretation of the parameters, and (iv) obtain analytic corrections due to kinetic effects given by a small number of terms and removing the numerical error of the evaluation of velocity phase space integrals. This work does not attempt to derive new physical effects even if it could be possible to discover one from the better understandings of some unsolved problems, but here we focus on the analytic prediction of kinetic corrections from analytic non-Maxwellians. As applications, examples of analytic kinetic corrections are shown for the secondary electron emission, the Langmuir probe characteristic curve, and the entropy. This is done by using three analytic representations of the distribution function: the Kappa distribution function, the bi-modal or a new interpreted non-Maxwellian distribution function (INMDF). The existence of INMDFs is proved by new understandings of the experimental discrepancy of the measured electron temperature between two diagnostics in JET. As main results, it is shown that (i) the empirical formula for the secondary electron emission is not consistent with a MDF due to the presence of super-thermal particles, (ii) the super-thermal particles can replace a diffusion parameter in the Langmuir probe current formula, and (iii) the entropy can explicitly decrease in presence of sources only for the introduced INMDF without violating the second law of thermodynamics. Moreover, the first order entropy of an infinite number of super-thermal tails stays the same as the entropy of a MDF. The latter demystifies the Maxwell's demon by statistically describing non-isolated systems.« less

The Unilateral Below Elbow Test: a function test for children with unilateral congenital below elbow deficiency.

PubMed

Bagley, Anita M; Molitor, Fred; Wagner, Lisa V; Tomhave, Wendy; James, Michelle A

2006-07-01

The Unilateral Below Elbow Test (UBET) was developed to evaluate function in bimanual activities for both the prosthesis wearer and non-wearer. Nine tasks were chosen for each of four age-specific categories defined by development stages of hand function (2-4y, 5-7y, 8-10y, and 11-21y). Two scales, Completion of Task and Method of Use, were designed to rate performance. To measure reliability, four occupational therapists scored samples of videotaped UBET performances. For Completion of Task, an interval scale, agreement in scoring was measured with interclass correlation coefficients (ICC; n=9; five females, four males). For Method of Use, a nominal scale, chance-adjusted association was calculated with Cohen's kappa coefficients (interobserver n=198; 111 females, 87 males; intraobserver n=93; 56 females, 37 males). For Completion of Task, the average ICC was 0.87 for the prosthesis-on condition, and 0.85 for the prosthesis-off condition. ICCs exceeded 0.80 for eight out of nine tasks for the two older age groups, but for only five out of nine tasks in the younger age groups. Higher inter- and intraobserver kappa coefficients for Method of Use resulted when scoring children with their prostheses on versus off. The oldest age group had lower kappa values than the other three groups. The UBET is recommended for the functional evaluation of Completion of Task in children with unilateral congenital below elbow deficiency with and without their prostheses. Method of Use scoring can evaluate individuals for directed therapy interventions or prosthetic training.

Nitric oxide sensitizes prostate carcinoma cell lines to TRAIL-mediated apoptosis via inactivation of NF-kappa B and inhibition of Bcl-xl expression.

PubMed

Huerta-Yepez, Sara; Vega, Mario; Jazirehi, Ali; Garban, Hermes; Hongo, Fumiya; Cheng, Genhong; Bonavida, Benjamin

2004-06-24

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to be selective in the induction of apoptosis in cancer cells with minimal toxicity to normal tissues and this prompted its potential therapeutic application in cancer. However, not all cancers are sensitive to TRAIL-mediated apoptosis and, therefore, TRAIL-resistant cancer cells must be sensitized first to become sensitive to TRAIL. Treatment of prostate cancer (CaP) cell lines (DU145, PC-3, CL-1, and LNCaP) with nitric oxide donors (e.g. (Z)-1-[2-(2-aminoethyl)-N-(2-ammonio-ethyl)amino]diazen-1-ium-1, 2-diolate (DETANONOate)) sensitized CaP cells to TRAIL-induced apoptosis and synergy was achieved. The mechanism by which DETANONOate mediated the sensitization was examined. DETANONOate inhibited the constitutive NF-kappa B activity as assessed by EMSA. Also, p50 was S-nitrosylated by DETANONOate resulting in inhibition of NF-kappa B. Inhibition of NF-kappa B activity by the chemical inhibitor Bay 11-7085, like DETANONOate, sensitized CaP to TRAIL apoptosis. In addition, DETANONOate downregulated the expression of Bcl-2 related gene (Bcl-(xL)) which is under the transcriptional regulation of NF-kappa B. The regulation of NF-kappa B and Bcl-(xL) by DETANONOate was corroborated by the use of Bcl-(xL) and Bcl-x kappa B reporter systems. DETANONOate inhibited luciferase activity in the wild type and had no effect on the mutant cells. Inhibition of NF-kappa B resulted in downregulation of Bcl-(xL) expression and sensitized CaP to TRAIL-induced apoptosis. The role of Bcl-(xL) in the regulation of TRAIL apoptosis was corroborated by inhibiting Bcl-(xL) function by the chemical inhibitor 2-methoxyantimycin A(3) and this resulted in sensitization of the cells to TRAIL apoptosis. Signaling by DETANONOate and TRAIL for apoptosis was examined. DETANONOate altered the mitochondria by inducing membrane depolarization and releasing modest amounts of cytochrome c and Smac/DIABLO in the absence of downstream activation of caspases 9 and 3. However, the combination of DETANONOate and TRAIL resulted in activation of the mitochondrial pathway and activation of caspases 9 and 3, and induction of apoptosis. These findings demonstrate that DETANONOate-mediated sensitization of CaP to TRAIL-induced apoptosis is via inhibition of constitutive NF-kappa B activity and Bcl-(xL) expression.

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.

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.

Existence regimes for shocks in inhomogeneous magneto-plasmas having entropy

NASA Astrophysics Data System (ADS)

Iqbal, Javed; Yaqub Khan, M.

2018-04-01

The finding of connection of plasma density and temperature with entropy gives an incitement to study different plasma models with respect to entropy. Nonlinear dissipative one- and two-dimensional structures (shocks) are investigated in nonuniform magnetized plasma with respect to entropy. The dissipation comes in the medium through ion-neutral collisions. The linear dispersion relation is derived. The Korteweg-deVries-Burgers and Kadomtsev-Petviashvili-Burgers equations are derived for nonlinear drift waves in 1-D and 2-D by employing the drift approximation. It is found that vd/u ( vd is the diamagnetic drift velocity and u is the velocity of nonlinear structure) plays a significant role in the shock formation. It is also found that entropy has a significant effect on the strength of shocks. It is noticed that v d/u determines the rarefactive and compressive nature of the shocks. It is observed that upper and lower bounds exist for the shock velocity. It is also observed that the existing regimes for both one- and two-dimensional shocks for kappa distributed electrons are different from shocks with Cairns distributed electrons. Both rarefactive and compressive shocks are found for the 1-D drift waves with kappa distributed electrons. Interestingly, it is noticed that entropy enhances the strength of one- and two-dimensional shocks.

DIFFUSE AURORA ON GANYMEDE DRIVEN BY ELECTROSTATIC WAVES

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

Singhal, R. P.; Tripathi, A. K.; Halder, S.

The role of electrostatic electron cyclotron harmonic (ECH) waves in producing diffuse auroral emission O i 1356 Å on Ganymede is investigated. Electron precipitation flux entering the atmosphere of Ganymede due to pitch-angle diffusion by ECH waves into the atmospheric loss-cone is calculated. The analytical yield spectrum approach for electron energy degradation in gases is used for calculating diffuse auroral intensities. It is found that calculated O i 1356 Å intensity resulting from the precipitation of magnetospheric electrons observed near Ganymede is insufficient to account for the observed diffuse auroral intensity. This is in agreement with estimates made in earliermore » works. Heating and acceleration of ambient electrons by ECH wave turbulence near the magnetic equator on the field line connecting Ganymede and Jupiter are considered. Two electron distribution functions are used to simulate the heating effect by ECH waves. Use of a Maxwellian distribution with temperature 100 eV can produce about 50–70 Rayleigh O i 1356 Å intensities, and the kappa distribution with characteristic energy 50 eV also gives rise to intensities with similar magnitude. Numerical experiments are performed to study the effect of ECH wave spectral intensity profile, ECH wave amplitude, and temperature/characteristic energy of electron distribution functions on the calculated diffuse auroral intensities. The proposed missions, joint NASA/ESA Jupiter Icy Moon Explorer and the present JUNO mission to Jupiter, would provide new data to constrain the ECH wave and other physical parameters near Ganymede. These should help confirm the findings of the present study.« less

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.

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.

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.

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.

Application of a Third Order Upwind Scheme to Viscous Flow over Clean and Iced Wings

NASA Technical Reports Server (NTRS)

Bangalore, A.; Phaengsook, N.; Sankar, L. N.

1994-01-01

A 3-D compressible Navier-Stokes solver has been developed and applied to 3-D viscous flow over clean and iced wings. This method uses a third order accurate finite volume scheme with flux difference splitting to model the inviscid fluxes, and second order accurate symmetric differences to model the viscous terms. The effects of turbulence are modeled using a Kappa-epsilon model. In the vicinity of the sold walls the kappa and epsilon values are modeled using Gorski's algebraic model. Sampling results are presented for surface pressure distributions, for untapered swept clean and iced wings made of NACA 0012 airfoil sections. The leading edge of these sections is modified using a simulated ice shape. Comparisons with experimental data are given.

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, and for a transonic turbine vane with transition and heat transfer. Results were compared to the B-L model and to experimental data.

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

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

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.

Particulate wear debris activates protein tyrosine kinases and nuclear factor kappaB, which down-regulates type I collagen synthesis in human osteoblasts.

PubMed

Vermes, C; Roebuck, K A; Chandrasekaran, R; Dobai, J G; Jacobs, J J; Glant, T T

2000-09-01

Particulate wear debris generated mechanically from prosthetic materials is phagocytosed by a variety of cell types within the periprosthetic space including osteoblasts, which cells with an altered function may contribute to periprosthetic osteolysis. Exposure of osteoblast-like osteosarcoma cells or bone marrow-derived primary osteoblasts to either metallic or polymeric particles of phagocytosable sizes resulted in a marked decrease in the steady-state messenger RNA (mRNA) levels of procollagen alpha1[I] and procollagen alpha1[III]. In contrast, no significant effect was observed for the osteoblast-specific genes, such as osteonectin and osteocalcin (OC). In kinetic studies, particles once phagocytosed, maintained a significant suppressive effect on collagen gene expression and type I collagen synthesis for up to five passages. Large particles of a size that cannot be phagocytosed also down-regulated collagen gene expression suggesting that an initial contact between cells and particles can generate gene responsive signals independently of the phagocytosis process. Concerning such signaling, titanium particles rapidly increased protein tyrosine phosphorylation and nuclear transcription factor kappaB (NF-kappaB) binding activity before the phagocytosis of particles. Protein tyrosine kinase (PTK) inhibitors such as genistein and the NF-kappaB inhibitor pyrrolidine dithiocarbamate (PDTC) significantly reduced the suppressive effect of titanium on collagen gene expression suggesting particles suppress collagen gene expression through the NF-kappaB signaling pathway. These results provide a mechanism by which particulate wear debris can antagonize the transcription of the procollagen alpha1[I] gene in osteoblasts, which may contribute to reduced bone formation and progressive periprosthetic osteolysis.

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.

Automated selection of BI-RADS lesion descriptors for reporting calcifications in mammograms

NASA Astrophysics Data System (ADS)

Paquerault, Sophie; Jiang, Yulei; Nishikawa, Robert M.; Schmidt, Robert A.; D'Orsi, Carl J.; Vyborny, Carl J.; Newstead, Gillian M.

2003-05-01

We are developing an automated computer technique to describe calcifications in mammograms according to the BI-RADS lexicon. We evaluated this technique by its agreement with radiologists' description of the same lesions. Three expert mammographers reviewed our database of 90 cases of digitized mammograms containing clustered microcalcifications and described the calcifications according to BI-RADS. In our study, the radiologists used only 4 of the 5 calcification distribution descriptors and 5 of the 14 calcification morphology descriptors contained in BI-RADS. Our computer technique was therefore designed specifically for these 4 calcification distribution descriptors and 5 calcification morphology descriptors. For calcification distribution, 4 linear discriminant analysis (LDA) classifiers were developed using 5 computer-extracted features to produce scores of how well each descriptor describes a cluster. Similarly, for calcification morphology, 5 LDAs were designed using 10 computer-extracted features. We trained the LDAs using only the BI-RADS data reported by the first radiologist and compared the computer output to the descriptor data reported by all 3 radiologists (for the first radiologist, the leave-one-out method was used). The computer output consisted of the best calcification distribution descriptor and the best 2 calcification morphology descriptors. The results of the comparison with the data from each radiologist, respectively, were: for calcification distribution, percent agreement, 74%, 66%, and 73%, kappa value, 0.44, 0.36, and 0.46; for calcification morphology, percent agreement, 83%, 77%, and 57%, kappa value, 0.78, 0.70, and 0.44. These results indicate that the proposed computer technique can select BI-RADS descriptors in good agreement with radiologists.

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.

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.

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

Qian, Y. Z., E-mail: qyzbird@live.com; Chen, H., E-mail: hchen61@ncu.edu.cn; Liu, S. Q., E-mail: sqlgroup@ncu.edu.cn

The Jeans instability in self-gravitating plasma with Kappa distributed dust grains is investigated basing on assumption that the mutual interaction among dust grains is governed by Lennard-Jones potential. It is shown that the presence of additional suprathermal particles has significant effects on the range of unstable modes and growth rate of Jeans instability. Compared with Maxwellian scenario, suprathermality stabilized the Jeans instability.

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.

Measurement Comparisons Towards Improving the Understanding of Aerosol-Cloud Processing

NASA Astrophysics Data System (ADS)

Noble, Stephen R.

Cloud processing of aerosol is an aerosol-cloud interaction that is not heavily researched but could have implications on climate. The three types of cloud processing are chemical processing, collision and coalescence processing, and Brownian capture of interstitial particles. All types improve cloud condensation nuclei (CCN) in size or hygroscopicity (kappa). These improved CCN affect subsequent clouds. This dissertation focuses on measurement comparisons to improve our observations and understanding of aerosol-cloud processing. Particle size distributions measured at the continental Southern Great Plains (SGP) site were compared with ground based measurements of cloud fraction (CF) and cloud base altitude (CBA). Particle size distributions were described by a new objective shape parameter to define bimodality rather than an old subjective one. Cloudy conditions at SGP were found to be correlated with lagged shape parameter. Horizontal wind speed and regional CF explained 42%+ of this lag time. Many of these surface particle size distributions were influenced by aerosol-cloud processing. Thus, cloud processing may be more widespread with more implications than previously thought. Particle size distributions measured during two aircraft field campaigns (MArine Stratus/stratocumulus Experiment; MASE; and Ice in Cloud Experiment-Tropical; ICE-T) were compared to CCN distributions. Tuning particle size to critical supersaturation revealed hygroscopicity expressed as ? when the distributions were overlain. Distributions near cumulus clouds (ICE-T) had a higher frequency of the same ?s (48% in ICE-T to 42% in MASE) between the accumulation (processed) and Aitken (unprocessed) modes. This suggested physical processing domination in ICE-T. More MASE (stratus cloud) kappa differences between modes pointed to chemical cloud processing. Chemistry measurements made in MASE showed increases in sulfates and nitrates with distributions that were more processed. This supported chemical cloud processing in MASE. This new method to determine kappa provides the needed information without interrupting ambient measurements. MODIS derived cloud optical thickness (COT), cloud liquid water path (LWP), and cloud effective radius (re) were compared to the same in situ derived variables from cloud probe measurements of two stratus/stratocumulus cloud campaigns (MASE and Physics Of Stratocumulus Tops; POST). In situ data were from complete vertical cloud penetrations, while MODIS data were from pixels along the aircraft penetration path. Comparisons were well correlated except that MODIS LWP (14-36%) and re (20-30%) were biased high. The LWP bias was from re bias and was not improved by using the vertically stratified assumption. MODIS re bias was almost removed when compared to cloud top maximum in situ re, but, that does not describe re for the full depth of the cloud. COT is validated by in situ COT. High correlations suggest that MODIS variables are useful in self-comparisons such as gradient changes in stratus cloud re during aerosol-cloud processing.

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

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.

The Rosseland Mean Opacity in Dense Plasmas

NASA Astrophysics Data System (ADS)

van Horn, H. M.

1992-05-01

In post-main-sequence phases of stellar evolution, densities in the interiors of stars become large enough so that hbar omega_p /kT>1, where omega_p is the electron plasma frequency. The plasma is thus a strongly dispersive medium at frequencies near the peak of the Planck function, and only photons with frequencies omega >omega_p can propagate in the plasma. These effects must be taken into account in computing radiative transfer in stellar interiors. Here I first identify several late evolutionary stages in which these effects may be significant. Then I use the formalism Harris 1965 has developed to treat radiative transfer in a dispersive medium in order to derive the resulting modification of the Rosseland mean opacity kappa_R . The resulting expression is the same as that presented (without a full derivation) by Aharony & Opher 1979, who interpreted the frequency-dependent absorption coefficient kappa_ ω as that in vacuo. However, the absorption coefficient in a plasma scales from that in vacuum according to the relation kappa_ ω=n_ω(-1) kappa_ ω((vac)) (Bekefi 1966, p. 52), where n_ω equiv (kc/omega ) = [1-(omega_p (2/) omega (2)right ](1/2)) is the index of refraction of the plasma. With this correction, we find the Rosseland mean opacity to be given by the expression {1\\over \\kappa_R}={{\\int_{\\omega_p}^{\\infty} {n_{\\omega}^3 \\over \\kappa_{\\omega}^{(vac)}}{partial B_{\\omega} \\over partial T} \\bigg|_{\\omega} d\\omega} \\over{\\int_0^{\\infty}{partial B_{\\omega} \\over partial T} \\bigg|_{\\omega} d\\omega}}. This research has been supported in part by NASA grant NAGW-2444 and in part by NSF grant AST 91-15132. \\centerline{References} Aharony, U., and Opher, R. 1979, A&A, 79, 27. Bekefi, G. 1966, Radiation Processes in Plasmas, (John Wiley & Sons, Inc.: New York). Harris, E. G. 1965, Phys. Rev., 138, B479.

A quantitative study of NF-kappaB activation by H2O2: relevance in inflammation and synergy with TNF-alpha.

PubMed

de Oliveira-Marques, Virgínia; Cyrne, Luísa; Marinho, H Susana; Antunes, Fernando

2007-03-15

Although the germicide role of H(2)O(2) released during inflammation is well established, a hypothetical regulatory function, either promoting or inhibiting inflammation, is still controversial. In particular, after 15 years of highly contradictory results it remains uncertain whether H(2)O(2) by itself activates NF-kappaB or if it stimulates or inhibits the activation of NF-kappaB by proinflammatory mediators. We investigated the role of H(2)O(2) in NF-kappaB activation using, for the first time, a calibrated and controlled method of H(2)O(2) delivery--the steady-state titration--in which cells are exposed to constant, low, and known concentrations of H(2)O(2). This technique contrasts with previously applied techniques, which disrupt cellular redox homeostasis and/or introduce uncertainties in the actual H(2)O(2) concentration to which cells are exposed. In both MCF-7 and HeLa cells, H(2)O(2) at extracellular concentrations up to 25 microM did not induce significantly per se NF-kappaB translocation to the nucleus, but it stimulated the translocation induced by TNF-alpha. For higher H(2)O(2) doses this stimulatory role shifts to an inhibition, which may explain published contradictory results. The stimulatory role was confirmed by the observation that 12.5 microM H(2)O(2), a concentration found during inflammation, increased the expression of several proinflammatory NF-kappaB-dependent genes induced by TNF-alpha (e.g., IL-8, MCP-1, TLR2, and TNF-alpha). The same low H(2)O(2) concentration also induced the anti-inflammatory gene coding for heme oxygenase-1 (HO-1) and IL-6. We propose that H(2)O(2) has a fine-tuning regulatory role, comprising both a proinflammatory control loop that increases pathogen removal and an anti-inflammatory control loop, which avoids an exacerbated harmful inflammatory response.

Nuclear factor kappa B role in inflammation associated gastrointestinal malignancies

PubMed Central

Gambhir, Sahil; Vyas, Dinesh; Hollis, Michael; Aekka, Apporva; Vyas, Arpita

2015-01-01

Nuclear factor kappa B (NF-κB) has an established role in the regulation of innate immunity and inflammation. NF-κB is also involved in critical mechanisms connecting inflammation and cancer development. Recent investigations suggest that the NF-κB signaling cascade may be the central mediator of gastrointestinal malignancies including esophageal, gastric and colorectal cancers. This review will explore NF-κB’s function in inflammation-associated gastrointestinal malignancies, highlighting its oncogenic contribution to each step of carcinogenesis. NF-κB’s role in the inflammation-to-carcinoma sequence in gastrointestinal malignancies warrants stronger emphasis upon targeting this pathway in achieving greater therapeutic efficacy. PMID:25805923

Impact of turbulence anisotropy near walls in room airflow.

PubMed

Schälin, A; Nielsen, P V

2004-06-01

The influence of different turbulence models used in computational fluid dynamics predictions is studied in connection with room air movement. The turbulence models used are the high Re-number kappa-epsilon model and the high Re-number Reynolds stress model (RSM). The three-dimensional wall jet is selected for the work. The growth rate parallel to the wall in a three-dimensional wall jet is large compared with the growth rate perpendicular to the wall, and it is large compared with the growth rate in a free circular jet. It is shown that it is not possible to predict the high growth rate parallel with a surface in a three-dimensional wall jet by the kappa-epsilon turbulence model. Furthermore, it is shown that the growth rate can be predicted to a certain extent by the RSM with wall reflection terms. The flow in a deep room can be strongly influenced by details as the growth rate of a three-dimensional wall jet. Predictions by a kappa-epsilon model and RSM show large deviations in the occupied zone. Measurements and observations of streamline patterns in model experiments indicate that a reasonable solution is obtained by the RSM compared with the solution obtained by the kappa-epsilon model. Computational fluid dynamics (CFD) is often used for the prediction of air distribution in rooms and for the evaluation of thermal comfort and indoor air quality. The most used turbulence model in CFD is the kappa-epsilon model. This model often produces good results; however, some cases require more sophisticated models. The prediction of a three-dimensional wall jet is improved if it is made by a Reynolds stress model (RSM). This model improves the prediction of the velocity level in the jet and in some special cases it may influence the entire flow in the occupied zone.

Lateralized kappa opioid receptor signaling from the amygdala central nucleus promotes stress-induced functional pain.

PubMed

Nation, Kelsey M; De Felice, Milena; Hernandez, Pablo I; Dodick, David W; Neugebauer, Volker; Navratilova, Edita; Porreca, Frank

2018-05-01

The response of diffuse noxious inhibitory controls (DNIC) is often decreased, or lost, in stress-related functional pain syndromes. Because the dynorphin/kappa opioid receptor (KOR) pathway is activated by stress, we determined its role in DNIC using a model of stress-induced functional pain. Male, Sprague-Dawley rats were primed for 7 days with systemic morphine resulting in opioid-induced hyperalgesia. Fourteen days after priming, when hyperalgesia was resolved, rats were exposed to environmental stress and DNIC was evaluated by measuring hind paw response threshold to noxious pressure (test stimulus) after capsaicin injection in the forepaw (conditioning stimulus). Morphine priming without stress did not alter DNIC. However, stress produced a loss of DNIC in morphine-primed rats in both hind paws that was abolished by systemic administration of the KOR antagonist, nor-binaltorphimine (nor-BNI). Microinjection of nor-BNI into the right, but not left, central nucleus of the amygdala (CeA) prevented the loss of DNIC in morphine-primed rats. Diffuse noxious inhibitory controls were not modulated by bilateral nor-BNI in the rostral ventromedial medulla. Stress increased dynorphin content in both the left and right CeA of primed rats, reaching significance only in the right CeA; no change was observed in the rostral ventromedial medulla or hypothalamus. Although morphine priming alone is not sufficient to influence DNIC, it establishes a state of latent sensitization that amplifies the consequences of stress. After priming, stress-induced dynorphin/KOR signaling from the right CeA inhibits DNIC in both hind paws, likely reflecting enhanced descending facilitation that masks descending inhibition. Kappa opioid receptor antagonists may provide a new therapeutic strategy for stress-related functional pain disorders.

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

Zhao, Yu; Wang, Wenhui; Wang, Qi

Highlights: Black-Right-Pointing-Pointer 5-LOX is able to upregulate expression of NF-{kappa}B p65. Black-Right-Pointing-Pointer 5-LOX enhances nuclear translocation of NF-{kappa}B p65 via increasing p-I{kappa}B-{alpha} level. Black-Right-Pointing-Pointer 5-LOX stimulates transcriptional activity of NF-{kappa}B in hepatoma cells. Black-Right-Pointing-Pointer LTB4 activates transcriptional activity of NF-{kappa}B in hepatoma cells. -- Abstract: The issue that lipid metabolism enzyme and its metabolites regulate transcription factors in cancer cell is not fully understood. In this study, we first report that the lipid metabolism enzyme 5-Lipoxygenase (5-LOX) and its metabolite leukotriene B4 (LTB4) are capable of activating nuclear factor-{kappa}B (NF-{kappa}B) in hepatoma cells. We found that the treatment of MK886more » (an inhibitor of 5-LOX) or knockdown of 5-LOX was able to downregulate the expression of NF-{kappa}B p65 at the mRNA level and decreased the phosphorylation level of inhibitor {kappa}B{alpha} (I{kappa}B{alpha}) in the cytoplasm of hepatoma HepG2 or H7402 cells, which resulted in the decrease of the level of nuclear NF-{kappa}B p65. These were confirmed by immunofluorescence staining in HepG2 cell. Moreover, the above treatments were able to decrease the transcriptional activity of NF-{kappa}B in the cells. The LTB4, one of metabolites of 5-LOX, is responsible for 5-LOX-activated NF-{kappa}B in a dose-dependent manner. Thus, we conclude that the lipid metabolism enzyme 5-LOX and its metabolite LTB4 are capable of activating transcription factor NF-{kappa}B in hepatoma cells. Our finding provides new insight into the significance of lipid metabolism in activation of transcription factors in cancer.« less

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...

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...

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

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.

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

Allescher, H.D.; Ahmad, S.; Classen, M.

Receptor binding of the opioid receptor antagonist, ({sup 3}H)diprenorphine, which has a similar affinity to the various opioid receptor subtypes, was characterized in subcellular fractions derived from either longitudinal or circular smooth muscle of the canine small intestine with their plexuses (myenteric plexus and deep muscular plexus, respectively) attached. The distribution of opioid binding activity showed a good correlation in the different fractions with the binding of the neuronal marker ({sup 3}H)saxitoxin but no correlation to the smooth muscle plasma membrane marker 5'-nucleotidase. The saturation data (Kd = 0.12 +/- 0.04 nM and maximum binding = 400 +/- 20 fmol/mg)more » and the data from kinetic experiments (Kd = 0.08 nmol) in the myenteric plexus were in good agreement with results obtained previously from the circular muscle/deep muscular plexus preparation. Competition experiments using selective drugs for mu (morphiceptin-analog (N-MePhe3-D-Pro4)-morphiceptin), delta (D-Pen2,5-enkephalin) and kappa (dynorphin 1-13, U50488-H) ligands showed the existence of all three receptor subtypes. The existence of kappa receptors was confirmed in saturation experiments using ({sup 3}H) ethylketocycloazocine as labeled ligand. Two putative opioid agonists, with effects on gastrointestinal motility, trimebutine and JO-1196 (fedotozin), were also examined. Trimebutine (Ki = 0.18 microM), Des-Met-trimebutine (Ki = 0.72 microM) and Jo-1196 (Ki = 0.19 microM) displaced specific opiate binding. The relative affinity for the opioid receptor subtypes was mu = 0.44, delta = 0.30 and kappa = 0.26 for trimebutine and mu = 0.25, delta = 0.22 and kappa = 0.52 for Jo-1196.« less

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

Synthesis, structural studies and reactivity of vanadium complexes with tridentate (OSO) ligand.

PubMed

Janas, Zofia; Wiśniewska, Dorota; Jerzykiewicz, Lucjan B; Sobota, Piotr; Drabent, Krzysztof; Szczegot, Krzysztof

2007-05-28

The direct reaction between [VCl(3)(thf)3] or [VO(OEt)3] and 2,2'-thiobis{4-(1,1,3,3-tetramethyl-butyl)phenol (tbopH(2)) leads to the formation of [V(2)(micro-tbop-kappa(3)O,S,O)2Cl(2)(CH(3)CN)(2)] (1).4CH(3)CN or [V(2)(micro-OEt)2(O)2(tbop-kappa(3)O,S,O)2] (2), respectively, in high yield. Compounds 1 and 2 were characterized by chemical and physical techniques including X-ray crystallography and variable temperature magnetic susceptibility studies (J = -29.1 cm(-1)) for 1. Complexes 1 and 2 were supported on MgCl2 and when activated with aluminium alkyls, were found to effectively polymerize ethene to produce polyethylene with a narrow molecular weight distribution M(w)/M(n) approximately 3.

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.

Charging of Interstellar Dust Grains in the out-of-equilibrium Heliosheath Plasma traced by IBEX ENAs

NASA Astrophysics Data System (ADS)

Frisch, P. C.; Ogasawara, K.; Livadiotis, G.; Slavin, J. D.; McComas, D. J.; Funsten, H. O.; Schwadron, N.; Heerikhuisen, J.

2017-12-01

Dusty bow waves are common around stars and anticipated around the heliosphere due to the deficit of low-mass interstellar dust grains in the inner heliosphere. Interstellar grains entering the heliosphere must first cross barriers of non-Maxwellian plasma in the heliosheath regions where collisional charging of grains is highly effective. IBEX measures 0.1-6 keV ENAs in the heliosheath plasma, providing an in situ sample of the heliosheath plasma thermodynamics that can be used for grain-charging calculations. Plasma in three-quarters of the sky can be described with a stationary state kappa-distribution, giving predictions for kappa, kappa-distribution temperature, and plasma density [1]. This thermodynamic description allows a more realistic evaluation of the dominant heliosheath electron and ion currents, and hence also grain gyroradii and exclusion from the heliosphere. At the highest temperatures ion collisional currents dominate grain charging; at lower temperatures collisional electron currents are more important together with the photoelectric ejection of electrons. An absence of data on the thermodynamical state of heliosheath electrons has led to the assumption of similar thermodynamic parameters for the electron and ion populations. The balance between electron, proton and photoionization currents on the grains then yield the equilibrium grain charges. Grain gyroradii calculated based on these charging currents differentiate between interstellar grains able to penetrate the heliosphere, versus those that are excluded, and allow predictions of properties of the dusty bow wave likely to be present around the heliosphere. The smallest grains are excluded and grains at the high latitude edges of the described regions tend to have systematically lower grain potentials. Grain charging calculations utilize the modeling of [2]. [1] Livadiotis et al., ApJ 734, 1 (2011). [2] Weingartner Draine, ApJSS 263 (2001)

Evaluating Mesorectal Lymph Nodes in Rectal Cancer Before and After Neoadjuvant Chemoradiation Using Thin-Section T2-Weighted Magnetic Resonance Imaging

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

Koh, Dow-Mu; Chau, Ian; Tait, Diana

2008-06-01

Purpose: To apply thin-section T2-weighted magnetic resoance imaging (MRI) to evaluate the number, size, distribution, and morphology of benign and malignant mesorectal lymph nodes before and after chemoradiation treatment compared with histopathologic findings. Methods and Materials: Twenty-five patients with poor-risk adenocarcinoma of the rectum treated with neoadjuvant chemoradiation were evaluated prospectively. Thin-section T2-weighted MR images obtained before and after chemoradiation treatment were independently reviewed in consensus by 2 expert radiologists to determine the tumor stage, nodal size, nodal distribution, and nodal stage. Total mesorectal excision surgery after chemoradiation allowed MR nodal stage to be compared with histopathology using {kappa} statistics.more » Nodal downstaging was compared using the Chi-square test. Results: Before chemoradiation, 152 mesorectal nodes were visible (mean, 6.2 mm; 100 benign, 52 malignant) and 4 of 52 malignant nodes were in contact with the mesorectal fascia. The nodal staging was 7/25 N0, 10/25 N1, and 7/25 N2. After chemoradiation, only 29 nodes (mean, 4.1 mm; 24 benign, 5 malignant) were visible, and none were in contact with the mesorectal fascia. Nodal downstaging was observed: 20/25 N0 and 5/25 N1 (p < 0.01, Chi-square test). There was good agreement between MRI and pathologic T-staging ({kappa} = 0.64) and N-staging ({kappa} = 0.65) after chemoradiation. Conclusions: Neoadjuvant chemoradiation treatment resulted in a decrease in size and number of malignant- and benign-appearing mesorectal nodes on MRI. Nodal downstaging and nodal regression from the mesorectal fascia were observed after treatment. MRI is a useful tool for assessing nodal response to neoadjuvant treatment.« less

Increased ventilatory variability and complexity in patients with hyperventilation disorder.

PubMed

Bokov, Plamen; Fiamma, Marie-Noëlle; Chevalier-Bidaud, Brigitte; Chenivesse, Cécile; Straus, Christian; Similowski, Thomas; Delclaux, Christophe

2016-05-15

It has been hypothesized that hyperventilation disorders could be characterized by an abnormal ventilatory control leading to enhanced variability of resting ventilation. The variability of tidal volume (VT) often depicts a nonnormal distribution that can be described by the negative slope characterizing augmented breaths formed by the relationship between the probability density distribution of VT and VT on a log-log scale. The objectives of this study were to describe the variability of resting ventilation [coefficient of variation (CV) of VT and slope], the stability in respiratory control (loop, controller and plant gains characterizing ventilatory-chemoresponsiveness interactions) and the chaotic-like dynamics (embedding dimension, Kappa values characterizing complexity) of resting ventilation in patients with a well-defined dysfunctional breathing pattern characterized by air hunger and constantly decreased PaCO2 during a cardiopulmonary exercise test. Compared with 14 healthy subjects with similar anthropometrics, 23 patients with hyperventilation were characterized by increased variability of resting tidal ventilation (CV of VT median [interquartile]: 26% [19-35] vs. 36% [28-48], P = 0.020; slope: -6.63 [-7.65; -5.36] vs. -3.88 [-5.91; -2.66], P = 0.004) that was not related to increased chemical drive (loop gain: 0.051 [0.039-0.221] vs. 0.044 [0.012-0.087], P = 0.149) but that was related to an increased ventilatory complexity (Kappa values, P < 0.05). Plant gain was decreased in patients and correlated with complexity (with Kappa 5 - degree 5: Rho = -0.48, P = 0.006). In conclusion, well-defined patients suffering from hyperventilation disorder are characterized by increased variability of their resting ventilation due to increased ventilatory complexity with stable ventilatory-chemoresponsiveness interactions. Copyright © 2016 the American Physiological Society.

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.

Application of stochastic processes in random growth and evolutionary dynamics

NASA Astrophysics Data System (ADS)

Oikonomou, Panagiotis

We study the effect of power-law distributed randomness on the dynamical behavior of processes such as stochastic growth patterns and evolution. First, we examine the geometrical properties of random shapes produced by a generalized stochastic Loewner Evolution driven by a superposition of a Brownian motion and a stable Levy process. The situation is defined by the usual stochastic Loewner Evolution parameter, kappa, as well as alpha which defines the power-law tail of the stable Levy distribution. We show that the properties of these patterns change qualitatively and singularly at critical values of kappa and alpha. It is reasonable to call such changes "phase transitions". These transitions occur as kappa passes through four and as alpha passes through one. Numerical simulations are used to explore the global scaling behavior of these patterns in each "phase". We show both analytically and numerically that the growth continues indefinitely in the vertical direction for alpha greater than 1, goes as logarithmically with time for alpha equals to 1, and saturates for alpha smaller than 1. The probability density has two different scales corresponding to directions along and perpendicular to the boundary. Scaling functions for the probability density are given for various limiting cases. Second, we study the effect of the architecture of biological networks on their evolutionary dynamics. In recent years, studies of the architecture of large networks have unveiled a common topology, called scale-free, in which a majority of the elements are poorly connected except for a small fraction of highly connected components. We ask how networks with distinct topologies can evolve towards a pre-established target phenotype through a process of random mutations and selection. We use networks of Boolean components as a framework to model a large class of phenotypes. Within this approach, we find that homogeneous random networks and scale-free networks exhibit drastically different evolutionary paths. While homogeneous random networks accumulate neutral mutations and evolve by sparse punctuated steps, scale-free networks evolve rapidly and continuously towards the target phenotype. Moreover, we show that scale-free networks always evolve faster than homogeneous random networks; remarkably, this property does not depend on the precise value of the topological parameter. By contrast, homogeneous random networks require a specific tuning of their topological parameter in order to optimize their fitness. This model suggests that the evolutionary paths of biological networks, punctuated or continuous, may solely be determined by the network topology.

The symmetric quartic map for trajectories of magnetic field lines in elongated divertor tokamak plasmas

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

Jones, Morgin; Wadi, Hasina; Ali, Halima

The coordinates of the area-preserving map equations for integration of magnetic field line trajectories in divertor tokamaks can be any coordinates for which a transformation to ({psi}{sub t},{theta},{phi}) coordinates exists [A. Punjabi, H. Ali, T. Evans, and A. Boozer, Phys. Lett. A 364, 140 (2007)]. {psi}{sub t} is toroidal magnetic flux, {theta} is poloidal angle, and {phi} is toroidal angle. This freedom is exploited to construct the symmetric quartic map such that the only parameter that determines magnetic geometry is the elongation of the separatrix surface. The poloidal flux inside the separatrix, the safety factor as a function of normalizedmore » minor radius, and the magnetic perturbation from the symplectic discretization are all held constant, and only the elongation is {kappa} varied. The width of stochastic layer, the area, and the fractal dimension of the magnetic footprint and the average radial diffusion coefficient of magnetic field lines from the stochastic layer; and how these quantities scale with {kappa} is calculated. The symmetric quartic map gives the correct scalings which are consistent with the scalings of coordinates with {kappa}. The effects of m=1, n={+-}1 internal perturbation with the amplitude that is expected to occur in tokamaks are calculated by adding a term [H. Ali, A. Punjabi, A. H. Boozer, and T. Evans, Phys. Plasmas 11, 1908 (2004)] to the symmetric quartic map. In this case, the width of stochastic layer scales as 0.35 power of {kappa}. The area of the footprint is roughly constant. The average radial diffusion coefficient of field lines near the X-point scales linearly with {kappa}. The low mn perturbation changes the quasisymmetric structure of the footprint, and reorganizes it into a single, large scale, asymmetric structure. The symmetric quartic map is combined with the dipole map [A. Punjabi, H. Ali, and A. H. Boozer, Phys. Plasmas 10, 3992 (2003)] to calculate the effects of magnetic perturbation from a current carrying coil. The coil position and coil current coil are constant. The dipole perturbation enhances the magnetic shear. The width of the stochastic layer scales exponentially with {kappa}. The area of the footprint decreases as the {kappa} increases. The radial diffusion coefficient of field lines scales exponentially with {kappa}. The dipole perturbation changes the topology of the footprint. It breaks up the toroidally spiraling footprint into a number of separate asymmetric toroidal strips. Practical applications of the symmetric quartic map to elongated divertor tokamak plasmas are suggested.« less

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.

Comparison modeling for alpine vegetation distribution in an arid area.

PubMed

Zhou, Jihua; Lai, Liming; Guan, Tianyu; Cai, Wetao; Gao, Nannan; Zhang, Xiaolong; Yang, Dawen; Cong, Zhentao; Zheng, Yuanrun

2016-07-01

Mapping and modeling vegetation distribution are fundamental topics in vegetation ecology. With the rise of powerful new statistical techniques and GIS tools, the development of predictive vegetation distribution models has increased rapidly. However, modeling alpine vegetation with high accuracy in arid areas is still a challenge because of the complexity and heterogeneity of the environment. Here, we used a set of 70 variables from ASTER GDEM, WorldClim, and Landsat-8 OLI (land surface albedo and spectral vegetation indices) data with decision tree (DT), maximum likelihood classification (MLC), and random forest (RF) models to discriminate the eight vegetation groups and 19 vegetation formations in the upper reaches of the Heihe River Basin in the Qilian Mountains, northwest China. The combination of variables clearly discriminated vegetation groups but failed to discriminate vegetation formations. Different variable combinations performed differently in each type of model, but the most consistently important parameter in alpine vegetation modeling was elevation. The best RF model was more accurate for vegetation modeling compared with the DT and MLC models for this alpine region, with an overall accuracy of 75 % and a kappa coefficient of 0.64 verified against field point data and an overall accuracy of 65 % and a kappa of 0.52 verified against vegetation map data. The accuracy of regional vegetation modeling differed depending on the variable combinations and models, resulting in different classifications for specific vegetation groups.

Bowel habit reference values and abnormalities in young Iranian healthy adults.

PubMed

Adibi, Peyman; Behzad, Ebrahim; Pirzadeh, Shahryar; Mohseni, Masood

2007-08-01

The purpose of this study was to estimate the prevalence of self-reported, ROME II-defined constipation and determine the average defecation frequency and stool types in the Iranian population. A self-reported questionnaire was distributed to 1045 participants, including items intended to identify the presence of ROME II-defined functional constipation and the dominant form of stool based on the Bristol Scale. The weekly mean bowel movement frequency in men and women was 12.5 +/- 7.3 and 13.8 +/- 8.0, respectively (p < 0.05). A total of 87.4% of participants had a stool frequency of between 3 and 21 times per week. The prevalence of functional constipation was 32.9%, whereas only 9.6% of participants reported themselves to be constipated (level of agreement kappa = 0.21, 95% confidence interval: 0.15 to 0.27). Soft or formed stool was reported in 75.7% of individuals. Functional constipation is common in the Iranian population, but its diagnosis could not rely on subjective patient complaints. Despite a higher average of bowel frequency, the previously reported normal range of defecation frequency can be applied for the Iranian population.

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.

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.

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)

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.

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.

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.

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

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.

Exact Dissipative Moment Closures for Simulation of Magnetospheric Plasmas

NASA Astrophysics Data System (ADS)

Newman, D. L.; Sen, N.; Goldman, M. V.

2004-11-01

Dissipative fluid closures produce a kinetic-like plasma response in simulations based on the evolution of moments of the Vlasov equation. Such methods were previously shown to approximate the kinetic susceptibility of a Maxwellian plasma.(G. W. Hammett and F. W. Perkins Phys. Rev. Lett.) 64, 3019 (1990). We show here that dissipative closures can yield the exact linear response for kappa velocity distributions (i.e., f(v)∝(v^2+w^2)^-κ in 1-D, where w∝ v_th), provided κ is an integer and κ+1 moments are retained in the closure. This finding is particularly relevant to the simulation of collisionless space plasmas, which frequently exhibit power-law tails characteristic of kappa distributions. Such dissipative algorithms can be made energy conserving by evolving the thermal parameter w. Dominant nonlinearities (e.g., ponderomotive effects) can also be incorporated into the algorithm. These methods have proven especially valuable in the context of reduced 2-D Vlasov simulations,(N. Sen, et al., Reduced 2-D Vlasov Simulationsldots), this meeting. where they have been used to model perpendicular ion dynamics in the evolution of nonlinear structures (e.g., double layers) in the auroral ionosphere.

Radiation-induced interleukin-6 expression through MAPK/p38/NF-kappaB signaling pathway and the resultant antiapoptotic effect on endothelial cells through Mcl-1 expression with sIL6-Ralpha.

PubMed

Chou, Chia-Hung; Chen, Shee-Uan; Cheng, Jason Chia-Hsien

2009-12-01

To investigate the mechanism of interleukin-6 (IL-6) activity induced by ionizing radiation. Human umbilical vascular endothelial cells (HUVECs) were irradiated with different doses to induce IL-6. The IL-6 promoter assay and reverse transcriptase-polymerase chain reaction (RT-PCR) were used to examine transcriptional regulation. Specific chemical inhibitors, decoy double-stranded oligodeoxynucleotides, and Western blotting were conducted to investigate the signal transduction pathway. Recombinant soluble human IL-6 receptor alpha-chain (sIL6-Ralpha) and specific small interfering RNA were used to evaluate the biologic function of radiation-induced IL-6. Four grays of radiation induced the highest level of IL-6 protein. The promoter assay and RT-PCR data revealed that the induction of IL-6 was mediated through transcriptional regulation. The p38 inhibitor SB203580, by blocking nuclear factor-kappaB (NF-kappaB) activation, prevented both the transcriptional and translational regulation of radiation-induced IL-6 expression. The addition of sIL6-Ralpha rescued HUVECs from radiation-induced death in an IL-6 concentratio-dependent manner. The antiapoptotic effect of combined sIL6-Ralpha and radiation-induced IL-6 was inhibited by mcl-1-specific small interfering RNA. Radiation transcriptionally induces IL-6 expression in endothelial cells through mitogen-activated protein kinase/p38-mediated NF-kappaB/IkappaB (inhibitor of NF-kappaB) complex activation. In the presence of sIL6-Ralpha, radiation-induced IL-6 expression acts through Mcl-1 expression to rescue endothelial cells from radiation-induced death.

[Primary investigation of the relationship between glucocorticoid induced leucine zipper and inflammatory reaction].

PubMed

Bai, Xiang-jun; Li, Bo; Wang, Hai-ping; Yang, Zhao-hui; Li, Si-qi

2007-01-01

To investigate the mechanism of the action of glucocorticoid induced leucine zipper (GILZ) in inflammatory reaction. Human monocyte cell line THP-1 cells were divided into two groups and cultured in non-serum RPMI1640 medium.In one group the cells were treated with dexamethasone (DEX). Twelve hours later total RNA and total protein were abstracted in both two groups. The mRNA encoding for expression of GILZ was semiquantitatively detected by reserve transcriptase-polymerase chain reaction (RT-PCR). Protein expression of nuclear factor-KappaB (NF-KappaB) p65 and activator protein-1 (AP-1) were assessed by Western blotting. Peripheral blood of 10 trauma patients [injury severity score (ISS) >or=16 scores] were collected and the leukocytes were isolated within 24 hours after trauma. The leukocytes were divided into two groups and cultured in non-serum medium. In one group the cells were treated with DEX. Twelve hours later total RNA and total protein were abstracted in both two groups. The mRNA encoding for expression of GILZ was semiquantitatively detected by RT-PCR. Protein expression of NF-KappaB p65 and AP-1 were assessed by Western blotting. Stimulated by DEX, the expression of GILZ mRNA was increased both in THP-1 cells and the leukocytes of trauma patients compared with those of control groups (both P<0.01). Whereas, protein expressions of NF-KappaB p65 and AP-1 of THP-1 cells and leukocytes in peripheral blood of trauma patients were decreased in the stimulation groups compared with those of control groups (all P<0.01). The expression of GILZ gene is up-regulated by glucocorticoid. Overexpression of GILZ inhibits NF-KappaB and AP-1 activities, suggesting that GILZ possesses anti-inflammatory function.

Daily peer review of abnormal cervical smears in the assessment of individual practice as an additional method of internal quality control.

PubMed

Confortini, M; Di Stefano, C; Biggeri, A; Bulgaresi, P; Di Claudio, G; Grisotto, L; Maddau, C; Matucci, M; Petreschi, C; Troni, G M; Turco, P; Foxi, P

2016-02-01

An important internal quality control system used in the Cancer Prevention and Research Institute cytopathology laboratory in Florence is the peer review procedure, based on the review of all abnormal cytological smears which routinely emerge. Peer review is an important training opportunity for all cytologists, especially for those with less experience. This article shows the results of the peer review procedure. Of the 63 754 Papanicolaou (Pap) smears screened in 2011, 1086 were considered to be abnormal [at least atypical squamous cells of undetermined significance (ASC-US+)] on primary screening (selected by a single cytologist) and were subjected to the peer review procedure. The overall performance of the laboratory's cytologists was evaluated using a multiple rater analysis and the comparison of each cytologist with the final diagnosis. Further, the agreement was assessed by means of Cohen's kappa and weighted kappa statistics. In general, a moderate/substantial level of agreement between the ten cytologists and the final diagnoses was evident. Kappa values for each reader compared with the final diagnosis ranged from 0.54 to 0.69. The overall kappa value was 0.62 [95% confidence interval (CI), 0.58-0.66] and overall weighted kappa value was 0.76 (95% CI, 0.74-0.79). The category-specific agreement showed the lowest values for atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H). In summary, peer review represents an important internal quality control in the evaluation and improvement of inter-observer agreement and of the functioning of the laboratory as a whole. Multi-head microscope sessions may improve particularly the reproducibility of borderline diagnoses and, above all, can be an important training contribution for cytologists. © 2014 John Wiley & Sons Ltd.

Specific LPA receptor subtype mediation of LPA-induced hypertrophy of cardiac myocytes and involvement of Akt and NFkappaB signal pathways.

PubMed

Chen, Jinghai; Chen, Yuefeng; Zhu, Weiquan; Han, Yu; Han, Bianmei; Xu, Ruixia; Deng, Linzi; Cai, Yan; Cong, Xiangfeng; Yang, Yuejing; Hu, Shengshou; Chen, Xi

2008-04-15

Lysophosphatidic acid (LPA) is a bioactive phospholipid with diverse functions mediated via G-protein-coupled receptors (GPCRs). In view of the elevated levels of LPA in acute myocardial infarction (MI) patients we have conducted studies aimed at identifying specific LPA receptor subtypes and signaling events that may mediate its actions in hypertrophic remodeling. Experiments were carried out in cultured neonatal rat cardiomyocytes (NRCMs) exposed to LPA and in a rat MI model. In NRCMs, LPA-induced hypertrophic growth was completely abrogated by DGPP, an LPA1/LPA3 antagonist. The LPA3 agonist OMPT, but not the LPA2 agonist dodecylphosphate, promoted hypertrophy as examined by 3[H]-Leucine incorporation, ANF-luciferase expression and cell area. In in vivo experiments, LPA1, LPA2 and LPA3 mRNA levels as well as LPA1 and LPA3 protein levels increased together with left ventricular remodeling (LVRM) after MI. In addition, LPA stimulated the phosphorylation of Akt and p65 protein and activated NF-kappaB-luciferase expression. Inhibitors of PI3K (wortmannin), mTOR (rapamycin), and NF-kappaB (PDTC or SN50) effectively prevented LPA-induced 3[H]-Leucine incorporation and ANF-luciferase expression. Furthermore, ERK inhibitors (U0126 and PD98059) suppressed LPA-stimulated activation of NF-kappaB and p65 phosphorylation whereas wortmannin showed no effect on NF-kappaB activation. Our findings indicate that LPA3 and/or LPA1 mediate LPA-induced hypertrophy of NRCMs and that LPA1 and LPA3 may be involved in LVRM of MI rats. Moreover, Akt and NF-kappaB signaling pathways independently implicate in LPA-stimulated myocardial hypertrophic growth.

Inter-observer agreement for diagnostic classification of esophageal motility disorders defined in high-resolution manometry.

PubMed

Fox, M R; Pandolfino, J E; Sweis, R; Sauter, M; Abreu Y Abreu, A T; Anggiansah, A; Bogte, A; Bredenoord, A J; Dengler, W; Elvevi, A; Fruehauf, H; Gellersen, S; Ghosh, S; Gyawali, C P; Heinrich, H; Hemmink, M; Jafari, J; Kaufman, E; Kessing, K; Kwiatek, M; Lubomyr, B; Banasiuk, M; Mion, F; Pérez-de-la-Serna, J; Remes-Troche, J M; Rohof, W; Roman, S; Ruiz-de-León, A; Tutuian, R; Uscinowicz, M; Valdovinos, M A; Vardar, R; Velosa, M; Waśko-Czopnik, D; Weijenborg, P; Wilshire, C; Wright, J; Zerbib, F; Menne, D

2015-01-01

High-resolution esophageal manometry (HRM) is a recent development used in the evaluation of esophageal function. Our aim was to assess the inter-observer agreement for diagnosis of esophageal motility disorders using this technology. Practitioners registered on the HRM Working Group website were invited to review and classify (i) 147 individual water swallows and (ii) 40 diagnostic studies comprising 10 swallows using a drop-down menu that followed the Chicago Classification system. Data were presented using a standardized format with pressure contours without a summary of HRM metrics. The sequence of swallows was fixed for each user but randomized between users to avoid sequence bias. Participants were blinded to other entries. (i) Individual swallows were assessed by 18 practitioners (13 institutions). Consensus agreement (≤ 2/18 dissenters) was present for most cases of normal peristalsis and achalasia but not for cases of peristaltic dysmotility. (ii) Diagnostic studies were assessed by 36 practitioners (28 institutions). Overall inter-observer agreement was 'moderate' (kappa 0.51) being 'substantial' (kappa > 0.7) for achalasia type I/II and no lower than 'fair-moderate' (kappa >0.34) for any diagnosis. Overall agreement was somewhat higher among those that had performed >400 studies (n = 9; kappa 0.55) and 'substantial' among experts involved in development of the Chicago Classification system (n = 4; kappa 0.66). This prospective, randomized, and blinded study reports an acceptable level of inter-observer agreement for HRM diagnoses across the full spectrum of esophageal motility disorders for a large group of clinicians working in a range of medical institutions. Suboptimal agreement for diagnosis of peristaltic motility disorders highlights contribution of objective HRM metrics. © 2014 International Society for Diseases of the Esophagus.

Ameliorative effects of arctiin from Arctium lappa on experimental glomerulonephritis in rats.

PubMed

Wu, Jian-Guo; Wu, Jin-Zhong; Sun, Lian-Na; Han, Ting; Du, Jian; Ye, Qi; Zhang, Hong; Zhang, Yu-Guang

2009-11-01

Membranous glomerulonephritis (MGN) remains the most common cause of adult-onset nephrotic syndrome in the world and up to 40% of untreated patients will progress to end-stage renal disease. Although the treatment of MGN with immunosuppressants or steroid hormones can attenuate the deterioration of renal function, numerous treatment-related complications have also been established. In this study, the ameliorative effects of arctiin, a natural compound isolated from the fruits of Arctium lappa, on rat glomerulonephritis induced by cationic bovine serum albumin (cBSA) were determined. After oral administration of arctiin (30, 60, 120 mg/kgd) for three weeks, the levels of serum creatinine (Scr) and blood urea nitrogen (BUN) and 24-h urine protein content markedly decreased, while endogenous creatinine clearance rate (ECcr) significantly increased. The parameters of renal lesion, hypercellularity, infiltration of polymorphonuclear leukocyte (PMN), fibrinoid necrosis, focal and segmental proliferation and interstitial infiltration, were reversed. In addition, we observed that arctiin evidently reduced the levels of malondialdehyde (MDA) and pro-inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor (TNF-alpha), suppressed nuclear factor-kappaB p65 (NF-kappaB) DNA binding activity, and enhanced superoxide dismutase (SOD) activity. These findings suggest that the ameliorative effects of arctiin on glomerulonephritis is carried out mainly by suppression of NF-kappaB activation and nuclear translocation and the decreases in the levels of these pro-inflammatory cytokines, while SOD is involved in the inhibitory pathway of NF-kappaB activation. Arctiin has favorable potency for the development of an inhibitory agent of NF-kappaB and further application to clinical treatment of glomerulonephritis, though clinical studies are required.

Structural and functional characterization of a novel homodimeric three-finger neurotoxin from the venom of Ophiophagus hannah (king cobra).

PubMed

Roy, Amrita; Zhou, Xingding; Chong, Ming Zhi; D'hoedt, Dieter; Foo, Chun Shin; Rajagopalan, Nandhakishore; Nirthanan, Selvanayagam; Bertrand, Daniel; Sivaraman, J; Kini, R Manjunatha

2010-03-12

Snake venoms are a mixture of pharmacologically active proteins and polypeptides that have led to the development of molecular probes and therapeutic agents. Here, we describe the structural and functional characterization of a novel neurotoxin, haditoxin, from the venom of Ophiophagus hannah (King cobra). Haditoxin exhibited novel pharmacology with antagonism toward muscle (alphabetagammadelta) and neuronal (alpha(7), alpha(3)beta(2), and alpha(4)beta(2)) nicotinic acetylcholine receptors (nAChRs) with highest affinity for alpha(7)-nAChRs. The high resolution (1.5 A) crystal structure revealed haditoxin to be a homodimer, like kappa-neurotoxins, which target neuronal alpha(3)beta(2)- and alpha(4)beta(2)-nAChRs. Interestingly however, the monomeric subunits of haditoxin were composed of a three-finger protein fold typical of curaremimetic short-chain alpha-neurotoxins. Biochemical studies confirmed that it existed as a non-covalent dimer species in solution. Its structural similarity to short-chain alpha-neurotoxins and kappa-neurotoxins notwithstanding, haditoxin exhibited unique blockade of alpha(7)-nAChRs (IC(50) 180 nm), which is recognized by neither short-chain alpha-neurotoxins nor kappa-neurotoxins. This is the first report of a dimeric short-chain alpha-neurotoxin interacting with neuronal alpha(7)-nAChRs as well as the first homodimeric three-finger toxin to interact with muscle nAChRs.

Kappa distributions in Saturn's magnetosphere: energetic ion moments using Cassini/MIMI measurements

NASA Astrophysics Data System (ADS)

Dialynas, K.; Roussos, E.; Regoli, L.; Paranicas, C.; Krimigis, S. M.; Kane, M.; Mitchell, D. G.; Hamilton, D. C.

2017-12-01

Moments of the charged particle distribution function are a compact way of characterizing some of the properties of different magnetospheric regions. Following our previous analyses (Dialynas et al. 2009) and the techniques described in Dialynas et al. (2017), in the present study we use κ-Distribution fits to combine CHEMS (3 to 236 keV/e), LEMMS (0.024 < E < 18 MeV), and INCA (5.2 to >220 keV) H+ and O+ energetic ion spectra covering measurements made in 2004-2016 to calculate the >20 keV energetic ion moments inside Saturn's magnetosphere. We use the Khurana et al. [2007] magnetic field model to map the ion measurements to the equatorial plane and produce the equatorial distributions of all ion integral moments, focusing on partial density (n), integral intensity (In), partial pressure (P), integral energy intensity (IE); as well as the characteristic energy (Ec=Ie/In), Temperature and κ-index of these ions as a function of Local Time (00:00 to 24:00 hrs) and L-Shell (5-20 Rs). The Roelof and Skinner [2000] model is then utilized to retrieve the equatorial H+ and O+ P, n and T in both local time and L-shell. We find that a) although the PH+ and PO+ are nearly comparable, H+ have higher IE and In at all radial distances (L>5) and local times; b) the 12Η+, ΓΟ+), are consistent with the Arridge et al. [2009] results. Dialynas K. et al. 2009, JGR, 114, A01212 Dialynas K. et al. 2017, Elsevier, ISBN: 9780128046388 Khurana K. K. et al. 2007, AGU, abstract #P44A-01 Roelof E. & A. Skinner 2000, SSR, 91, 437-459 Arridge C. S. et al. 2009, PSS, 57, 2032-2047

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.

IκB kinase 2 determines oligodendrocyte loss by non-cell-autonomous activation of NF-κB in the central nervous system

PubMed Central

Raasch, Jenni; Zeller, Nicolas; van Loo, Geert; Merkler, Doron; Mildner, Alexander; Erny, Daniel; Knobeloch, Klaus-Peter; Bethea, John R.; Waisman, Ari; Knust, Markus; Del Turco, Domenico; Deller, Thomas; Blank, Thomas; Priller, Josef; Brück, Wolfgang

2011-01-01

The IκB kinase complex induces nuclear factor kappa B activation and has recently been recognized as a key player of autoimmunity in the central nervous system. Notably, IκB kinase/nuclear factor kappa B signalling regulates peripheral myelin formation by Schwann cells, however, its role in myelin formation in the central nervous system during health and disease is largely unknown. Surprisingly, we found that brain-specific IκB kinase 2 expression is dispensable for proper myelin assembly and repair in the central nervous system, but instead plays a fundamental role for the loss of myelin in the cuprizone model. During toxic demyelination, inhibition of nuclear factor kappa B activation by conditional ablation of IκB kinase 2 resulted in strong preservation of central nervous system myelin, reduced expression of proinflammatory mediators and a significantly attenuated glial response. Importantly, IκB kinase 2 depletion in astrocytes, but not in oligodendrocytes, was sufficient to protect mice from myelin loss. Our results reveal a crucial role of glial cell-specific IκB kinase 2/nuclear factor kappa B signalling for oligodendrocyte damage during toxic demyelination. Thus, therapies targeting IκB kinase 2 function in non-neuronal cells may represent a promising strategy for the treatment of distinct demyelinating central nervous system diseases. PMID:21310728

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

Kinetic corrections from analytic non-Maxwellian distribution functions in magnetized plasmas

DOE PAGES

Izacard, Olivier

2016-08-02

In magnetized plasma physics, almost all developed analytic theories assume a Maxwellian distribution function (MDF) and in some cases small deviations are described using the perturbation theory. The deviations with respect to the Maxwellian equilibrium, called kinetic effects, are required to be taken into account especially for fusion reactor plasmas. Generally, because the perturbation theory is not consistent with observed steady-state non-Maxwellians, these kinetic effects are numerically evaluated by very central processing unit (CPU)-expensive codes, avoiding the analytic complexity of velocity phase space integrals. We develop here a new method based on analytic non-Maxwellian distribution functions constructed from non-orthogonal basismore » sets in order to (i) use as few parameters as possible, (ii) increase the efficiency to model numerical and experimental non-Maxwellians, (iii) help to understand unsolved problems such as diagnostics discrepancies from the physical interpretation of the parameters, and (iv) obtain analytic corrections due to kinetic effects given by a small number of terms and removing the numerical error of the evaluation of velocity phase space integrals. This work does not attempt to derive new physical effects even if it could be possible to discover one from the better understandings of some unsolved problems, but here we focus on the analytic prediction of kinetic corrections from analytic non-Maxwellians. As applications, examples of analytic kinetic corrections are shown for the secondary electron emission, the Langmuir probe characteristic curve, and the entropy. This is done by using three analytic representations of the distribution function: the Kappa distribution function, the bi-modal or a new interpreted non-Maxwellian distribution function (INMDF). The existence of INMDFs is proved by new understandings of the experimental discrepancy of the measured electron temperature between two diagnostics in JET. As main results, it is shown that (i) the empirical formula for the secondary electron emission is not consistent with a MDF due to the presence of super-thermal particles, (ii) the super-thermal particles can replace a diffusion parameter in the Langmuir probe current formula, and (iii) the entropy can explicitly decrease in presence of sources only for the introduced INMDF without violating the second law of thermodynamics. Moreover, the first order entropy of an infinite number of super-thermal tails stays the same as the entropy of a MDF. In conclusion, the latter demystifies the Maxwell's demon by statistically describing non-isolated systems.« less

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

Biasi, Glenn; Anderson, John G

The parameter kappa was defined by Anderson and Hough (1984) to describe the high-frequency spectral roll-off of the strong motion seismic spectrum. In the work of Su et al., (1996) the numerical value of kappa estimated for sites near Yucca Mountain was small (~20 ms). The estimate obtained from these events has been applied through a rigorous methodology to develop design earthquake spectra with magnitude over 5.0. Smaller values of kappa lead to higher estimated ground motions in the methodology used by the Probabilistic Seismic Hazard Analysis (PSHA) for Yucca Mountain. An increase of 10 ms in kappa could resultmore » in a substantial decrease in the high frequency level of the predicted ground motions. Any parameter that plays such a critical role deserves close examination. Here, we study kappa and its associated uncertainties. The data set used by Su et al (1996) consisted of 12 M 2.8 to 4.5 earthquakes recorded at temporary stations deployed after the June 1992 Little Skull Mountain earthquake. The kappa elements of that study were revisited by Anderson and Su (MOL.20071203.0134) and substantially confirmed. One weakness of those studies is the limited data used. Few of these stations were on tuff or on Yucca Mountain itself. A decade of Southern Great Basin Digital Seismic Network (SGBDSN) recording has now yielded a larger body of on-scale, well calibrated digital ground motion records suitable for investigating kappa. We use the SGBDSN data to check some of the original assumptions, improve the statistical confidence of the conclusions, and determine values of kappa for stations on or near Yucca Mountain. The outstanding issues in kappa analysis, as they apply to Yucca Mountain, include: 1. The number itself. The kappa estimate near 20 msec from Su et al. (1996) and Anderson and Su (MOL.20071203.0134) is markedly smaller than is considered typical in California (Silva, 1995). The low kappa value has engineering consequences because when it is applied in ground motions analyses used in PSHA, it contributes to the extreme values of peak ground acceleration that the PSHA predicts. Also, in some areas precarious rock evidence indicates that no such accelerations have occurred. 2. The disagreement among analyses in the value of kappa. Previous reports indicate that smallest earthquakes yield kappa estimate 12-20 msec larger than average values from M3 to M4.5 aftershocks of Little Skull Mountain earthquake. 3. The source of kappa. Classically and in engineering usage, kappa is attributed largely to the upper tens or hundreds of meters at the recording site. However, borehole recordings imply that a significant contribution to kappa originates below several hundred meters depth. Also, when earthquakes are considered from a small source region, a true site effect should be common to all recordings. In fact kappa observations of LSM aftershocks to stations on Yucca Mountain and at network stations appear to vary greatly, as though much of kappa actually derives from near the seismic source. 4. The repository overburden contribution to kappa. PSHA estimated ground motions to a free surface at 300 meters depth with properties of confined rock at that depth. Rock mechanical and borehole estimates suggest that several milliseconds of the total kappa accrue between 300 meters to the surface. If estimates of kappa are small at the surface, little is left to reduce incident ground accelerations from the seismic source to the repository level. 5. The variability of kappa. In most cases parametric estimates of kappa have some range of values that fit the data equally well in a statistical sense, so errors in kappa estimates must be addressed. As noted above, kappa at a station also varies significantly for events from the same source area. 6. Are kappa values from small to moderate magnitude earthquakes appropriately applied to the larger, potentially damaging earthquakes of engineering concern? Put another way, is there a significant magnitude dependence in kappa? Questions 1 and 6 are of primary importance, but we find answers to several others in the course of our study. Data from southern Nevada are capable of resolving only some of these questions. In a global search, we identified data from the Japanese borehole accelerometer array KiKNet as most likely to address the questions of the shallow site structural contribution to kappa and the usefulness of moderate earthquake kappa estimates to predict strong ground motion.« less

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

Kim, Byung Hak; Lee, Jun-Young; Seo, Jee Hee

Nuclear factor (NF)-{kappa}B regulates a central common signaling for immunity and cell survival. Artemisolide (ATM) was previously isolated as a NF-{kappa}B inhibitor from a plant of Artemisia asiatica. However, molecular basis of ATM on NF-{kappa}B activation remains to be defined. Here, we demonstrate that ATM is a typical inhibitor of I{kappa}B kinase {beta} (IKK{beta}), resulting in inhibition of lipopolysaccharide (LPS)-induced NF-{kappa}B activation in RAW 264.7 macrophages. ATM inhibited the kinase activity of highly purified IKK{beta} and also LPS-induced IKK activity in the cells. Moreover, the effect of ATM on IKK{beta} activity was completely abolished by substitution of Cys-179 residue ofmore » IKK{beta} to Ala residue, indicating direct targeting site of ATM. ATM could inhibit I{kappa}B{alpha} phosphorylation in LPS-activated RAW 264.7 cells and subsequently prevent NF-{kappa}B activation. Further, we demonstrate that ATM down-regulates NF-{kappa}B-dependent TNF-{alpha} expression. Taken together, this study provides a pharmacological potential of ATM in NF-{kappa}B-dependent inflammatory disorders.« less

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

Izacard, Olivier

In magnetized plasma physics, almost all developed analytic theories assume a Maxwellian distribution function (MDF) and in some cases small deviations are described using the perturbation theory. The deviations with respect to the Maxwellian equilibrium, called kinetic effects, are required to be taken into account especially for fusion reactor plasmas. Generally, because the perturbation theory is not consistent with observed steady-state non-Maxwellians, these kinetic effects are numerically evaluated by very central processing unit (CPU)-expensive codes, avoiding the analytic complexity of velocity phase space integrals. We develop here a new method based on analytic non-Maxwellian distribution functions constructed from non-orthogonal basismore » sets in order to (i) use as few parameters as possible, (ii) increase the efficiency to model numerical and experimental non-Maxwellians, (iii) help to understand unsolved problems such as diagnostics discrepancies from the physical interpretation of the parameters, and (iv) obtain analytic corrections due to kinetic effects given by a small number of terms and removing the numerical error of the evaluation of velocity phase space integrals. This work does not attempt to derive new physical effects even if it could be possible to discover one from the better understandings of some unsolved problems, but here we focus on the analytic prediction of kinetic corrections from analytic non-Maxwellians. As applications, examples of analytic kinetic corrections are shown for the secondary electron emission, the Langmuir probe characteristic curve, and the entropy. This is done by using three analytic representations of the distribution function: the Kappa distribution function, the bi-modal or a new interpreted non-Maxwellian distribution function (INMDF). The existence of INMDFs is proved by new understandings of the experimental discrepancy of the measured electron temperature between two diagnostics in JET. As main results, it is shown that (i) the empirical formula for the secondary electron emission is not consistent with a MDF due to the presence of super-thermal particles, (ii) the super-thermal particles can replace a diffusion parameter in the Langmuir probe current formula, and (iii) the entropy can explicitly decrease in presence of sources only for the introduced INMDF without violating the second law of thermodynamics. Moreover, the first order entropy of an infinite number of super-thermal tails stays the same as the entropy of a MDF. In conclusion, the latter demystifies the Maxwell's demon by statistically describing non-isolated systems.« less

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

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

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

Short communication: molecular characterization of dog and cat p65 subunits of NF-kappaB.

PubMed

Ishikawa, Shingo; Takemitsu, Hiroshi; Li, Gebin; Mori, Nobuko; Yamamoto, Ichiro; Arai, Toshiro

2015-04-01

Nuclear factor kappa B (NF-κB) plays an important role in the immune system. The p65 subunit is an important part of NF-κB unit, and studies of dog and cat p65 subunits of NF-κB (dp65 and cp65) are important in understanding their immune function. In this study, we described the molecular characterization of dp65 and cp65. The dp65 and cp65 complementary DNA encoded 542 and 555 amino acids, respectively, showing a high sequence homology with the mammalian p65 subunit (>87.5%). Quantitative polymerase chain reaction revealed that the p65 messenger RNA is highly expressed in the dog stomach and cat heart and adipose tissue. Functional NF-κB promoter-luciferase reporter vectors revealed that our isolated dp65 and cp65 cDNA encodes a functionally active protein. Transiently expressed dp65 and cp65 up-regulated pro-inflammatory cytokine expression levels in dog and cat, respectively. These findings suggest that dp65 and cp65 play important roles in regulating immune function. Copyright © 2015 Elsevier Ltd. All rights reserved.

Fish species of greatest conservation need in wadeable Iowa streams: current status and effectiveness of Aquatic Gap Program distribution models

USGS Publications Warehouse

Sindt, Anthony R.; Pierce, Clay; Quist, Michael C.

2012-01-01

Effective conservation of fish species of greatest conservation need (SGCN) requires an understanding of species–habitat relationships and distributional trends. Thus, modeling the distribution of fish species across large spatial scales may be a valuable tool for conservation planning. Our goals were to evaluate the status of 10 fish SGCN in wadeable Iowa streams and to test the effectiveness of Iowa Aquatic Gap Analysis Project (IAGAP) species distribution models. We sampled fish assemblages from 86 wadeable stream segments in the Mississippi River drainage of Iowa during 2009 and 2010 to provide contemporary, independent fish species presence–absence data. The frequencies of occurrence in stream segments where species were historically documented varied from 0.0% for redfin shiner Lythrurus umbratilis to 100.0% for American brook lampreyLampetra appendix, with a mean of 53.0%, suggesting that the status of Iowa fish SGCN is highly variable. Cohen's kappa values and other model performance measures were calculated by comparing field-collected presence–absence data with IAGAP model–predicted presences and absences for 12 fish SGCN. Kappa values varied from 0.00 to 0.50, with a mean of 0.15. The models only predicted the occurrences of banded darterEtheostoma zonale, southern redbelly dace Phoxinus erythrogaster, and longnose daceRhinichthys cataractae more accurately than would be expected by chance. Overall, the accuracy of the twelve models was low, with a mean correct classification rate of 58.3%. Poor model performance probably reflects the difficulties associated with modeling the distribution of rare species and the inability of the large-scale habitat variables used in IAGAP models to explain the variation in fish species occurrences. Our results highlight the importance of quantifying the confidence in species distribution model predictions with an independent data set and the need for long-term monitoring to better understand the distributional trends and habitat associations of fish SGCN.

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.

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.

Identifying mangrove species and their surrounding land use and land cover classes using object-oriented approach with a lacunarity spatial measure

USGS Publications Warehouse

Myint, S.W.; Giri, C.P.; Wang, L.; Zhu, Z.; Gillete, S.C.

2008-01-01

Accurate and reliable information on the spatial distribution of mangrove species is needed for a wide variety of applications, including sustainable management of mangrove forests, conservation and reserve planning, ecological and biogeographical studies, and invasive species management. Remotely sensed data have been used for such purposes with mixed results. Our study employed an object-oriented approach with the use of a lacunarity technique to identify different mangrove species and their surrounding land use and land cover classes in a tsunami-affected area of Thailand using Landsat satellite data. Our results showed that the object-oriented approach with lacunarity-transformed bands is more accurate (over-all accuracy 94.2%; kappa coefficient = 0.91) than traditional per-pixel classifiers (overall accuracy 62.8%; and kappa coefficient = 0.57). Copyright ?? 2008 by Bellwether Publishing, Ltd. All rights reserved.

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.

Mechanical and solubility properties of bio-nanocomposite film of semi refined kappa carrageenan/ZnO nanoparticles

NASA Astrophysics Data System (ADS)

Saputri, Apriliana Eka; Praseptiangga, Danar; Rochima, Emma; Panatarani, Camellia; Joni, I. Made

2018-02-01

The aim of this present work is to develop semi refined kappa carrageenan based bio-nanocomposite film as an alternative to synthetic petroleum based food packaging materials. Among natural polymers, carrageenan is one of the most promising material, since it is a renewable bioresource. The ZnO nanoparticles (0.5%; 1.0%; 1.5% w/w carrageenan) was incorporated into carrageenan polymer to prepare bio-nanocomposite films, where ZnO acts as reinforcement for carrageenan matrix. The mechanical and solubility properties of the prepared films were investigated as a function of ZnO concentration. The results indicated that the addition of ZnO exhibits greater solubility compared to the neat film. The elongation at break is insignificantly different on the films with and without addition ZnO. The tensile strength of the film was highest for the sample with 0.5% ZnO. These mechanical and solubility properties suggest that bio-nanocomposite film of semi refined kappa carrageenan and nanoparticle ZnO can be effectively used as food packaging material.

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.

Pre- and postoperative radiotherapy for extremity soft tissue sarcoma: Evaluation of inter-observer target volume contouring variability among French sarcoma group radiation oncologists.

PubMed

Sargos, P; Charleux, T; Haas, R L; Michot, A; Llacer, C; Moureau-Zabotto, L; Vogin, G; Le Péchoux, C; Verry, C; Ducassou, A; Delannes, M; Mervoyer, A; Wiazzane, N; Thariat, J; Sunyach, M P; Benchalal, M; Laredo, J D; Kind, M; Gillon, P; Kantor, G

2018-04-01

The purpose of this study was to evaluate, during a national workshop, the inter-observer variability in target volume delineation for primary extremity soft tissue sarcoma radiation therapy. Six expert sarcoma radiation oncologists (members of French Sarcoma Group) received two extremity soft tissue sarcoma radiation therapy cases 1: one preoperative and one postoperative. They were distributed with instructions for contouring gross tumour volume or reconstructed gross tumour volume, clinical target volume and to propose a planning target volume. The preoperative radiation therapy case was a patient with a grade 1 extraskeletal myxoid chondrosarcoma of the thigh. The postoperative case was a patient with a grade 3 pleomorphic undifferentiated sarcoma of the thigh. Contour agreement analysis was performed using kappa statistics. For the preoperative case, contouring agreement regarding GTV, gross tumour volume GTV, clinical target volume and planning target volume were substantial (kappa between 0.68 and 0.77). In the postoperative case, the agreement was only fair for reconstructed gross tumour volume (kappa: 0.38) but moderate for clinical target volume and planning target volume (kappa: 0.42). During the workshop discussion, consensus was reached on most of the contour divergences especially clinical target volume longitudinal extension. The determination of a limited cutaneous cover was also discussed. Accurate delineation of target volume appears to be a crucial element to ensure multicenter clinical trial quality assessment, reproducibility and homogeneity in delivering RT. radiation therapy RT. Quality assessment process should be proposed in this setting. We have shown in our study that preoperative radiation therapy of extremity soft tissue sarcoma has less inter-observer contouring variability. Copyright © 2018 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

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

Saji, Chiaki; Higashi, Chizuka; Niinaka, Yasufumi

Highlights: Black-Right-Pointing-Pointer Constitutive NF-{kappa}B signaling is essential for the survival and growth of PEL cells. Black-Right-Pointing-Pointer NF-{kappa}B signaling is upregulated by the proteasome-dependent degradation of I{kappa}B{alpha}. Black-Right-Pointing-Pointer Proteasome inhibitors suppress NF-{kappa}B signaling and induce apoptosis in PEL cells through stabilization of I{kappa}B{alpha}. Black-Right-Pointing-Pointer Proteasome inhibitors suppress viral replication in PEL cells during lytic KSHV infection. -- Abstract: Primary effusion lymphoma (PEL) is an aggressive neoplasm caused by Kaposi's sarcoma-associated herpesvirus (KSHV). This study provides evidence that proteasomal activity is required for both survival of PEL cells stably harboring the KSHV genome and viral replication of KSHV. We evaluated the cytotoxicmore » effects of proteasome inhibitors on PEL cells. The proteasome inhibitors MG132, lactacystin, and proteasome inhibitor I dramatically inhibited cell proliferation and induced apoptosis of PEL cells through the accumulation of p21 and p27. Furthermore, proteasome inhibitors induced the stabilization of NF-{kappa}B inhibitory molecule (I{kappa}B{alpha}) and suppressed the transcriptional activity of NF-{kappa}B in PEL cells. The NF-{kappa}B specific inhibitor BAY11-7082 also induced apoptosis in PEL cells. The constitutive activation of NF-{kappa}B signaling is essential for the survival and growth of B cell lymphoma cells, including PEL cells. NF-{kappa}B signaling is upregulated by proteasome-dependent degradation of I{kappa}B{alpha}. The suppression of NF-{kappa}B signaling by proteasome inhibitors may contribute to the induction of apoptosis in PEL cells. In addition, proteasome activity is required for KSHV replication in KSHV latently infected PEL cells. MG132 reduced the production of progeny virus from PEL cells at low concentrations, which do not affect PEL cell growth. These findings suggest that proteasome inhibitors may represent a novel strategy for the treatment of KSHV infection and KSHV-associated lymphomas.« less

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.

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.

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.

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.

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

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

Chronic kidney disease among high school students of Kinshasa

PubMed Central

2012-01-01

Background Chronic kidney disease (CKD) is a major worldwide health problem. However, its burden among adolescents and young adults is unknown, especially in sub-Saharan Africa. The aim of this study was to investigate its prevalence in the school environment. The concordance of usual formulas used to estimate renal function was also assessed. Methods In an epidemiological cross sectional study, a random sample of 524 pupils (263 boys, mean age of 18.7 ± 1.4 years) from school environment of Kinshasa were studied. Recorded parameters of interest were anthropometric, proteinuria, serum creatinine and estimated glomerular filtration rate (eGFR) according to the Schwartz formula using uncalibrated creatinine levels from one random measurement. CKD was defined as the presence of kidney damage (daily proteinuria ≥ 300 mg) and/or reduced kidney function (eGFR < 60 ml/min/1.73 m2). Concordances between eGFR according to Schwartz, Cockcroft-Gault (C-G) indexed for BSA and modification of diet in renal disease (MDRD) study equations were computed using the kappa coefficient. Results The prevalence of CKD by the Schwartz formula was 1.5%. By stage, 0.8% had CKD stage 1 (proteinuria with normal eGFR) and 0.8% had CKD stage 3 (eGFR, 30 to 59 ml/min/1.73 m2). The prevalence of proteinuria ≥ 300 mg/day was 1% (one case had 2.7g/day). Agreement between eGFR according to Schwartz formula and the MDRD formula was excellent (kappa: 88.8%). Although correlations between all formulas were excellent (0.99; 0.87, and 0.89), agreement was poor between eGFR according to Schwartz and C-G indexed BSA equation (kappa: 52.7%) and, poorer with C-G unadjusted for BSA (kappa: 26.9%). Conclusion In the large African city of Kinshasa, 2% of high school students have CKD. This high prevalence rate emphasizes the need for appropriate detection and prevention measures in this vulnerable young age population group. PMID:22559052

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

Yamawaki, Hideyuki, E-mail: yamawaki@vmas.kitasato-u.ac.jp; Kameshima, Satoshi; Usui, Tatsuya

Highlights: Black-Right-Pointing-Pointer Chemerin is a novel adipocytokine with almost unknown function in vasculature. Black-Right-Pointing-Pointer Chemerin activates Akt/eNOS/NO pathways in endothelial cells. Black-Right-Pointing-Pointer Chemerin inhibits TNF-{alpha}-induced monocyte adhesion to endothelial cells. Black-Right-Pointing-Pointer Chemerin inhibits TNF-induced VCAM-1 via suppressing NF-{kappa}B and p38 signal. Black-Right-Pointing-Pointer Chemerin is anti-inflammatory through producing NO in vascular endothelium. -- Abstract: Chemerin is a recently identified adipocytokine which plays a role on inflammation and adipocytes metabolism. However, its function in vasculature is largely unknown. We examined the effects of chemerin on vascular endothelial inflammatory states. Treatment of human umbilical vein endothelial cells with chemerin (300 ng/ml, 20 min)more » induced phosphorylation of Akt (Ser473) and endothelial nitric oxide (NO) synthase (eNOS) (Ser1177). Consistently, chemerin increased intracellular cyclic GMP content. Pretreatment with chemerin (1-300 ng/ml, 24 h) significantly inhibited phosphorylation of nuclear factor (NF)-{kappa}B p65 (Ser536) and p38 as well as vascular cell adhesion molecule (VCAM)-1 expression induced by tumor necrosis factor (TNF)-{alpha} (5 ng/ml, 20 min-6 h). Inhibitor of NF-{kappa}B or p38 significantly inhibited the TNF-{alpha}-induced VCAM-1 expression. Chemerin also inhibited TNF-{alpha}-induced VCAM-1 expression in rat isolated aorta. Moreover, chemerin significantly inhibited monocytes adhesion to TNF-{alpha}-stimulated endothelial cells. The inhibitory effect of chemerin on TNF-{alpha}-induced VCAM-1 was reversed by a NOS inhibitor. Conversely, an NO donor, sodium nitroprusside significantly inhibited TNF-{alpha}-induced VCAM-1. The present results for the first time demonstrate that chemerin plays anti-inflammatory roles by preventing TNF-{alpha}-induced VCAM-1 expression and monocytes adhesion in vascular endothelial cells. The effect is mediated via inhibiting activation of NF-{kappa}B and p38 through stimulation of Akt/eNOS signaling and NO production.« less

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

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

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

Changing to AIS 2005 and agreement of injury severity scores in a trauma registry with scores based on manual chart review.

PubMed

Stewart, Kenneth E; Cowan, Linda D; Thompson, David M

2011-09-01

The Abbreviated Injury Scale (AIS) recently underwent a major revision from AIS 98 to AIS 05. AIS injury codes form the basis of widely used injury severity scores such as the injury severity score (ISS). ISS thresholds are often used in trauma case definitions and ISS is widely used in injury research to adjust for injury severity. This study evaluated changes from AIS 98 to AIS 05, the changes' effect on ISS distributions, and presents an application of the results. Injury descriptions from medical records of 137 randomly selected patients in the Oklahoma Trauma Registry (OTR) were obtained. A single trained coder used AIS 98 and AIS 05 to code each injury. ISS values were calculated and grouped into 4 categories: 1-8, 9-14, 16-24, >24. Paired ISS was compared using Kappa statistics and tests of symmetry. We identified common injury diagnoses for which AIS severity changed between versions. Estimates of the proportion of patients changing ISS groups were applied to the entire OTR to assess the impact on reporting and on a model for reimbursement. OTR AIS 98 and manual AIS 98-based ISS values had a weighted Kappa of 0.71. OTR AIS 98 and manual AIS 05-based ISS values had a Kappa of 0.58. Manual AIS 98 and manual AIS 05 ISS had the highest Kappa of 0.81, however, though the scores differed by only 1 ISS category, there were 30 discordant pairs. The distribution of these discordant pairs was not symmetrical (Bowker's S=30; df=6; p<0.0001) with AIS 05-based ISS values consistently shifted to a lower ISS category. Reductions in AIS severity and ISS values using AIS 05 were common for extremity fractures and thorax injuries. The results suggest fewer patients would be reported to the OTR or be eligible for reimbursement. Changing from AIS 98 to AIS 05 injury coding resulted in systematic changes in AIS codes and ISS. Specific injuries and body regions were differentially affected. Trauma registries and injury researchers that use AIS based injury coding can use this information to evaluate the potential impact of changes in AIS 2005. Copyright © 2010 Elsevier Ltd. All rights reserved.

Limitations on the applicability of FODO lattices for electron cooling

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

Bertsche, K.J.

1997-09-01

Assuming a KV beam distribution (a uniform distribution over an elliptical region of transverse phase space), the beam envelop equations are shown, where X and Y are the transverse beam sizes, {kappa} is the lens strength, K is the generalized beam perveance, and {epsilon} is the beam emittance. If we further assume operation in a space-charge dominated regime, the right most term can be ignored in each equation. In this case, particle flow will be laminar, and the above equations not only describe the envelope of the beam, but also the trajectory of the outermost particles.

Performance of a quality assurance program for assessing dental health in methamphetamine users.

PubMed

Dye, Bruce A; Harrell, Lauren; Murphy, Debra A; Belin, Thomas; Shetty, Vivek

2015-07-05

Systematic characterization of the dental consequences of methamphetamine (MA) abuse presupposes a rigorous quality assurance (QA) program to ensure the credibility of the data collected and the scientific integrity and validity of the clinical study. In this report we describe and evaluate the performance of a quality assurance program implemented in a large cross-sectional study of the dental consequences of MA use. A large community sample of MA users was recruited over a 30 month period during 2011-13 and received comprehensive oral examinations and psychosocial assessments by site examiners based at two large community health centers in Los Angeles. National Health and Nutrition Examination Survey (NHANES) protocols for oral health assessments were utilized to characterize dental disease. Using NHANES oral health quality assurance guidelines, examiner reliability statistics such as Cohen's Kappa coefficients and inter-class correlation coefficients were calculated to assess the magnitude of agreement between the site examiners and a reference examiner to ensure conformance and comparability with NHANES practices. Approximately 9% (n = 49) of the enrolled 574 MA users received a repeat dental caries and periodontal examination conducted by the reference examiner. There was high concordance between the reference examiner and the site examiners for identification of untreated dental disease (Kappa statistic values: 0.57-0.75, percent agreement 83-88%). For identification of untreated caries on at least 5 surfaces of anterior teeth, the Kappas ranged from 0.77 to 0.87, and percent agreement from 94 to 97%. The intra-class coefficients (ICCs) ranged from 0.87 to 89 for attachment loss across all periodontal sites assessed and the ICCs ranged from 0.79 to 0.81 for pocket depth. For overall gingival recession, the ICCs ranged from 0.88 to 0.91. When Kappa was calculated based on the CDC/AAP case definitions for severe periodontitis, inter-examiner reliability for site examiners was low (Kappa 0.27-0.67). Overall, the quality assurance program confirmed the procedural adherence of the quality of the data collected on the distribution of dental caries and periodontal disease in MA-users. Examiner concordance was higher for dental caries but lower for specific periodontal assessments.

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.

A content analysis of peripheral arterial disease patient-reported outcome measures using the International Classification of Functioning, Disability and Health.

PubMed

Osborne, Candice Lee; Kauvar, David Seth

2017-10-17

The purpose of this study was to link, classify and describe the content of peripheral arterial disease (PAD)-specific patient-reported outcome measures using the International Classification of Functioning. The results were then analyzed to determine if these assessments provide clinicians and researchers with a comprehensive understanding of the lived experience of patients with PAD. Each meaningful concept in identified PAD assessments was linked to the International Classification of Functioning, Disability and Health to determine included and excluded content areas. An overall perspective was assigned to each assessment item. Inter-rater reliability was established using a kappa statistic. The body functions component is most frequently addressed overall followed by the activities and participation component. International Classification of Functioning chapter and category distribution vary greatly between assessments and no assessment comprehensively examines community participation and relationships. The majority of the assessment items are of the health status-disability and quality of life perspectives. The results of this study suggest the need for the development of a comprehensive PAD assessment that includes a more even distribution of International Classification of Functioning topics and subtopics. A more comprehensive assessment would better capture the lived experience of this patient population. Implications for Rehabilitation A better understanding of the data collected using the current peripheral arterial disease-specific patient-reported outcome measures may contribute to the development of more comprehensive assessment tools that will ultimately lead to improved patient care. This study contributes to the preliminary foundation for the development of a peripheral arterial disease International Classification of Functioning, Disability and Health Core Set. Clinicians and researchers interested in using peripheral arterial disease-specific patient-reported outcome measures for clinical and research purposes can better understand what topics are included and excluded in the collection and what perspectives are addressed.

Reproducibility of peripapillary retinal nerve fiber layer thickness with spectral domain cirrus high-definition optical coherence tomography in normal eyes.

PubMed

Hong, Samin; Kim, Chan Yun; Lee, Won Seok; Seong, Gong Je

2010-01-01

To assess the reproducibility of the new spectral domain Cirrus high-definition optical coherence tomography (HD-OCT; Carl Zeiss Meditec, Dublin, CA, USA) for analysis of peripapillary retinal nerve fiber layer (RNFL) thickness in healthy eyes. Thirty healthy Korean volunteers were enrolled. Three optic disc cube 200 x 200 Cirrus HD-OCT scans were taken on the same day in discontinuous sessions by the same operator without using the repeat scan function. The reproducibility of the calculated RNFL thickness and probability code were determined by the intraclass correlation coefficient (ICC), coefficient of variation (CV), test-retest variability, and Fleiss' generalized kappa (kappa). Thirty-six eyes were analyzed. For average RNFL thickness, the ICC was 0.970, CV was 2.38%, and test-retest variability was 4.5 microm. For all quadrants except the nasal, ICCs were 0.972 or higher and CVs were 4.26% or less. Overall test-retest variability ranged from 5.8 to 8.1 microm. The kappa value of probability codes for average RNFL thickness was 0.690. The kappa values of quadrants and clock-hour sectors were lower in the nasal areas than in other areas. The reproducibility of Cirrus HD-OCT to analyze peripapillary RNFL thickness in healthy eyes was excellent compared with the previous reports for time domain Stratus OCT. For the calculated RNFL thickness and probability code, variability was relatively higher in the nasal area, and more careful analyses are needed.

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…

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...

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

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

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.

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

Improved modeling of turbulent forced convection heat transfer in straight ducts

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

Rokni, M.; Sunden, B.

1999-08-01

This investigation concerns numerical calculation of turbulent forced convective heat transfer and fluid flow in their fully developed state at low Reynolds number. The authors have developed a low Reynolds number version of the nonlinear {kappa}-{epsilon} model combined with the heat flux models of simple eddy diffusivity (SED), low Reynolds number version of generalized gradient diffusion hypothesis (GGDH), and wealth {proportional_to} earning {times} time (WET) in general three-dimensional geometries. The numerical approach is based on the finite volume technique with a nonstaggered grid arrangement and the SIMPLEC algorithm. Results have been obtained with the nonlinear {kappa}-{epsilon} model, combined with themore » Lam-Bremhorst and the Abe-Kondoh-Nagano damping functions for low Reynolds numbers.« less

Study of Quantum Chaos in the Framework of Triaxial Rotator Models

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

Proskurins, J.; Bavrins, K.; Andrejevs, A.

2009-01-28

Dynamical quantum chaos criteria--a perturbed wave function entropy W({psi}{sub i}) and a fragmentation width {kappa}({phi}{sub k}) of basis states were studied in two cases of nuclear rigid triaxial rotator models. The first model is characterized by deformation angle {gamma} only, while the second model depends on both quadrupole deformation parameters ({beta},{gamma}). The degree of chaoticity has been determined in the studies of the dependence of criteria W({psi}{sub i}) and {kappa}({phi}{sub k}) from nuclear spin values up to I{<=}101 for model parameters {gamma} and ({beta},{gamma}) correspondingly. The transition from librational to rotational type energy spectra has been considered for both modelsmore » as well.« less

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.

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

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

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.

Prospective assessment of interobserver agreement for defecography in fecal incontinence.

PubMed

Dobben, Annette C; Wiersma, Tjeerd G; Janssen, Lucas W M; de Vos, Rien; Terra, Maaike P; Baeten, Cor G; Stoker, Jaap

2005-11-01

The primary aim of our study was to determine the interobserver agreement of defecography in diagnosing enterocele, anterior rectocele, intussusception, and anismus in fecal-incontinent patients. The subsidiary aim was to evaluate the influence of level of experience on interpreting defecography. Defecography was performed in 105 consecutive fecal-incontinent patients. Observers were classified by level of experience and their findings were compared with the findings of an expert radiologist. The quality of the expert radiologist's findings was evaluated by an intraobserver agreement procedure. Intraobserver agreement was good to very good except for anismus: incomplete evacuation after 30 sec (kappa, 0.55) and puborectalis impression (kappa, 0.54). Interobserver agreement for enterocele and rectocele was good (kappa, 0.66 for both) and for intussusception, fair (kappa, 0.29). Interobserver agreement for anismus: incomplete evacuation after 30 sec was moderate (kappa, 0.47), and for anismus: puborectalis impression was fair (kappa, 0.24). Agreement in grading of enterocele and rectocele was good (kappa, 0.64 and 0.72, respectively) and for intussusception, fair (kappa, 0.39). Agreement separated by experience level was very good for rectocele (kappa, 0.83) and grading of rectoceles (kappa, 0.83) and moderate for intussusception (kappa, 0.44) at the most experienced level. For enterocele and grading, experience level did not influence the reproducibility. Reproducibility for enterocele, anterior rectocele, and severity grading is good, but for intussusception is fair to moderate. For anismus, the diagnosis of incomplete evacuation after 30 sec is more reproducible than puborectalis impression. The level of experience seems to play a role in diagnosing anterior rectocele and its grading and in diagnosing intussusception.

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

Inter-observer variability between general pathologists and a specialist in breast pathology in the diagnosis of lobular neoplasia, columnar cell lesions, atypical ductal hyperplasia and ductal carcinoma in situ of the breast.

PubMed

Gomes, Douglas S; Porto, Simone S; Balabram, Débora; Gobbi, Helenice

2014-06-19

This study aimed to assess inter-observer variability between the original diagnostic reports and later review by a specialist in breast pathology considering lobular neoplasias (LN), columnar cell lesions (CCL), atypical ductal hyperplasia (ADH), and ductal carcinoma in situ (DCIS) of the breast. A retrospective, observational, cross-sectional study was conducted. A total of 610 breast specimens that had been formally sent for consultation and/or second opinions to the Breast Pathology Laboratory of Federal University of Minas Gerais were analysed between January 2005 and December 2010. The inter-observer variability between the original report and later review was compared regarding the diagnoses of LN, CCL, ADH, and DCIS. Statistical analyses were conducted using the Kappa index. Weak correlations were observed for the diagnoses of columnar cell change (CCC; Kappa=0.38), columnar cell hyperplasia (CCH; Kappa=0.32), while a moderate agreement (Kappa=0.47) was observed for the diagnoses of flat epithelial atypia (FEA). Good agreement was observed in the diagnoses of atypical lobular hyperplasia (ALH; Kappa=0.62) and lobular carcinoma in situ (LCIS; Kappa=0.66). However, poor agreement was observed for the diagnoses of pleomorphic LCIS (Kappa=0.22). Moderate agreement was observed for the diagnoses of ADH (Kappa=0.44), low-grade DCIS (Kappa=0.47), intermediate-grade DCIS (Kappa=0.45), and DCIS with microinvasion (Kappa=0.56). Good agreement was observed between the diagnoses of high-grade DCIS (Kappa=0.68). According to our data, the best diagnostic agreements were observed for high-grade DCIS, ALH, and LCIS. CCL without atypia and pleomorphic LCIS had the worst agreement indices. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1640072350119725.

Synthesis, structure and reactivity of tetranuclear square-type complexes of rhenium and manganese bearing pyrimidine-2-thiolate (pymS) ligands: versatile and efficient precursors for mono- and polynuclear compounds containing M(CO)(3) (M = Re, Mn) fragments.

PubMed

Kabir, S E; Alam, J; Ghosh, S; Kundu, K; Hogarth, G; Tocher, D A; Hossain, G M G; Roesky, H W

2009-06-21

Reactions of M(2)(CO)(10) (M = Re, Mn) with pyrimidine-2-thiol (pymSH) in the presence of Me(3)NO afford the tetranuclear square-type complexes [M(4)(CO)(12)(micro-kappa(3)-pymS)(4)] (, M = Re; , M = Mn). Both consist of four M(CO)(3) (M = Re, Mn) units, pairs of which are joined by tridentate pyrimidine-2-thiolate ligands. Treatment of with a variety of donor ligands results in cleavage of the square to afford mononuclear species with either a mono- or bidentate pyrimidine-2-thiolate ligand. Triphenylphosphine reacts with to give [Mn(CO)(3)(PPh(3))(kappa(2)-pymS)] () in which the pyrimidine-2-thiolate coordinates in a bidentate fashion. With diamines [M(CO)(3)(kappa(2)-L)(kappa(1)-pymS)] () (M = Re, Mn; L = 2,2'- bipy, 1,10-phen, en) result in which the pyrimidine-2-thiolate binds in a monodentate fashion through sulfur. With diphosphines, complexes with different stoichiometries and pyrimidine-2-thiolate binding modes are obtained depending on the nature of the metal and diphosphine. With dppm and dppe, gives [Re(CO)(2)(kappa(1)-pymS)(kappa(2)-dppm)] () and [Re(CO)(2)(kappa(2)-pymS)(kappa(1)-dppe)(2)] (), respectively, whereas affords [Mn(CO)(2)(kappa(2)-pymS)(kappa(1)-dppm)(2)] () and [Mn(CO)(2)(kappa(2)-pyS)(kappa(2)-dppe)] () under similar conditions. Reactions of with [Os(3)(CO)(10)(NCMe)(2)] affords mixed-metal butterfly clusters [MOs(3)(CO)(13)(micro(3)-kappa(2)-pymS)] () in which the group 7 metal occupies a wing-tip position and the pyrimidine-2-thiolate ligand caps a triangular Os(2)M face. With Ru(3)(CO)(12), carbon-sulfur bond cleavage occurs to give the tetranuclear clusters [MRu(3)(CO)(14)(micro(4)-S)(micro-kappa(1):eta(1)-pym)] () bearing both the extruded sulfur and the heterocyclic ring. The molecular structures of , and have been established by X-ray diffraction allowing the binding mode of the pyrimidine-2-thiolate ligands to be probed.

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, which have been studied in the context of HIV-1 include the salicylates (sodium salicylate, and acetylsalicylic acid (aspirin)). Finally, the NF-kappaB DNA binding inhibitors, which have received attention only recently, are reviewed. These include the most potential, aurine tricarboxylic acid (ATA), a chelating agent, which has been found to inhibit NF-kappaB DNA binding at a low concentration of 30 micro M. The probable mechanism of action of these drugs is discussed alongwith relevant suggestions and conclusions.

Health professionals identify components of the International Classification of Functioning, Disability and Health (ICF) in questionnaires for the upper limb

PubMed Central

Philbois, Stella V.; Martins, Jaqueline; Souza, Cesário S.; Sampaio, Rosana F.; Oliveira, Anamaria S.

2016-01-01

BACKGROUND: Several Brazilian studies have addressed the International Classification of Functioning, Disability and Health (ICF), but few have analyzed the knowledge of the health professionals with regards to the ICF. OBJECTIVE: To verify whether the classification of the items in the Brazilian-Portuguese versions of The Shoulder Pain and Disability Index (SPADI) and The Disabilities Arm, Shoulder and Hand (DASH) questionnaires, obtained from health professionals who worked with patients having upper limb injuries, could be related to ICF components as defined by others studies. METHOD: There were 4 participants for the group "professionals with high familiarity of the ICF (PHF)" and 19 for the group of "professionals with some or no familiarity of the ICF (PSNF)". The participants judged whether the items on the two questionnaires belonged to the ICF body function, body structure or activity-participation component, and marked a confidence level for each trial using a numerical scale ranging from zero to 10. The items were classified by the discriminant content validity method using the Student'st-test and the Hochberg correction. The ratings were compared to the literature by the percentage of agreement and Kappa coefficient. RESULTS: The percentage of agreement of the rating from the PSNF and the PHF groups with the literature was equal to or greater than 77%. For the DASH, the agreement of the PSNF and PHF groups with the literature were, respectively, moderate (Kappa=0.46 to 0.48) and substantial (Kappa=0.62 to 0.70). CONCLUSIONS: Health professionals were able to correlate the three components of the ICF for most items on the 2 questionnaires, demonstrating some ease of understanding the ICF components. However, the relation of concept of pain with body function component is not clear for professional and deserves a more attentive approach. PMID:26786076

Noribogaine is a G-protein biased κ-opioid receptor agonist.

PubMed

Maillet, Emeline L; Milon, Nicolas; Heghinian, Mari D; Fishback, James; Schürer, Stephan C; Garamszegi, Nandor; Mash, Deborah C

2015-12-01

Noribogaine is the long-lived human metabolite of the anti-addictive substance ibogaine. Noribogaine efficaciously reaches the brain with concentrations up to 20 μM after acute therapeutic dose of 40 mg/kg ibogaine in animals. Noribogaine displays atypical opioid-like components in vivo, anti-addictive effects and potent modulatory properties of the tolerance to opiates for which the mode of action remained uncharacterized thus far. Our binding experiments and computational simulations indicate that noribogaine may bind to the orthosteric morphinan binding site of the opioid receptors. Functional activities of noribogaine at G-protein and non G-protein pathways of the mu and kappa opioid receptors were characterized. Noribogaine was a weak mu antagonist with a functional inhibition constants (Ke) of 20 μM at the G-protein and β-arrestin signaling pathways. Conversely, noribogaine was a G-protein biased kappa agonist 75% as efficacious as dynorphin A at stimulating GDP-GTP exchange (EC50=9 μM) but only 12% as efficacious at recruiting β-arrestin, which could contribute to the lack of dysphoric effects of noribogaine. In turn, noribogaine functionally inhibited dynorphin-induced kappa β-arrestin recruitment and was more potent than its G-protein agonistic activity with an IC50 of 1 μM. This biased agonist/antagonist pharmacology is unique to noribogaine in comparison to various other ligands including ibogaine, 18-MC, nalmefene, and 6'-GNTI. We predict noribogaine to promote certain analgesic effects as well as anti-addictive effects at effective concentrations>1 μM in the brain. Because elevated levels of dynorphins are commonly observed and correlated with anxiety, dysphoric effects, and decreased dopaminergic tone, a therapeutically relevant functional inhibition bias to endogenously released dynorphins by noribogaine might be worthy of consideration for treating anxiety and substance related disorders. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

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...

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...

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...

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.

The effects of nonuniform magnetic field strength on density flux and test particle transport in drift wave turbulence

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

Dewhurst, J. M.; Hnat, B.; Dendy, R. O.

2009-07-15

The extended Hasegawa-Wakatani equations generate fully nonlinear self-consistent solutions for coupled density n and vorticity {nabla}{sup 2}{phi}, where {phi} is electrostatic potential, in a plasma with background density inhomogeneity {kappa}=-{partial_derivative} ln n{sub 0}/{partial_derivative}x and magnetic field strength inhomogeneity C=-{partial_derivative} ln B/{partial_derivative}x. Finite C introduces interchange effects and {nabla}B drifts into the framework of drift turbulence through compressibility of the ExB and diamagnetic drifts. This paper addresses the direct computation of the radial ExB density flux {gamma}{sub n}=-n{partial_derivative}{phi}/{partial_derivative}y, tracer particle transport, the statistical properties of the turbulent fluctuations that drive {gamma}{sub n} and tracer motion, and analytical underpinnings. Systematic trends emergemore » in the dependence on C of the skewness of the distribution of pointwise {gamma}{sub n} and in the relative phase of density-velocity and density-potential pairings. It is shown how these effects, together with conservation of potential vorticity {pi}={nabla}{sup 2}{phi}-n+({kappa}-C)x, account for much of the transport phenomenology. Simple analytical arguments yield a Fickian relation {gamma}{sub n}=({kappa}-C)D{sub x} between the radial density flux {gamma}{sub n} and the radial tracer diffusivity D{sub x}, which is shown to explain key trends in the simulations.« less

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.

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.

Interobserver agreement on Poser's and the new McDonald's diagnostic criteria for multiple sclerosis.

PubMed

Zipoli, V; Portaccio, E; Siracusa, G; Pracucci, G; Sorbi, S; Amato, M P

2003-10-01

We assessed the interobserver agreement on the diagnosis of multiple sclerosis (MS) in a study sample consisting of 41 MS (15 relapsing remitting, two secondary progressive, five primary progressive and 19 presenting their first clinical attack) and three non-MS cases. Clinical and paraclinical information was recorded in standardized forms. Four neurologists were asked to make a diagnosis using Poser's and McDonald's criteria and to assess MRI scans according to the McDonald's guidelines. In terms of the kappa statistic (kappa), we found a moderate agreement on the overall diagnosis using both Poser's and McDonald's criteria (kappa, respectively 0.57 and 0.52). As for distinct diagnostic categories, we observed a moderate to substantial agreement for the three McDonald categories (range of kappa values 0.49-0.64) and a fair to substantial agreement for the nine Poser categories (range of kappa values 0.37-0.67). Taking into account clinical information, the agreement on dissemination over time was substantially higher (kappa = 0.69) than that found on dissemination over space (kappa = 0.46). In contrast, for MRI assessment, the agreement for spatial dissemination was substantial (kappa = 0.74) compared with the fair agreement (kappa = 0.25) yielded by dissemination over time. The new McDonald's criteria yield a good overall diagnostic reliability, and compare favourably with Poser's classification in terms of agreement on distinct diagnostic categories.

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.

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.

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

[Intra-rater Reliability for the Questionnaire on Activity Limitations and Participation Restrictions of Children With ADHD].

PubMed

Salamanca Duque, Luisa Matilde; Naranjo Aristizábal, María Mercedes; Gutiérrez Ríos, Gladys Helena; Prieto, Jaime Bayona

2014-03-01

Questionnaires for evaluating activity limitations and participation restrictions in children with ADHD (CLARP-TDAH) has recently been developed in Colombia, based on the suggestions made by the WHO from the International Classification of Functioning, Disability and Health (ICF), allowing clinical evaluation beyond an evaluation of the functionality and functioning of children in their family and school environments. Previous research with the questionnaire proved useful in the multidisciplinary approach of Colombian children with ADHD. This study determines the level of intra-rater reliability for questionnaires CLARP-TDAH Parents and Teachers. The study included a non-random sample of 203 Colombian children attending school and diagnosed with ADHD. Intra-rater reliability and the reproducibility of the results was determined using the Kappa index. The informants were parents and teachers. Kappa values >0.7 were obtained for the intra-rater reliability of the questionnaire domains of CLARP-TDAH Parents, while for CLARP-TDAH Teachers domains these values were >0.8. CLARP-TDAH questionnaires are a tool with a good level of intra-rater reliability, which allows a reliable assessment of activity limitations and participation restrictions in order to determine the level of functioning at home and school. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Functional Stability of the Human Kappa Opioid Receptor Reconstituted in Nanodiscs Revealed by a Time-Resolved Scintillation Proximity Assay

PubMed Central

Hansen, Randi Westh; Wang, Xiaole; Golab, Agnieszka; Bornert, Olivier; Oswald, Christine; Wagner, Renaud; Martinez, Karen Laurence

2016-01-01

Long-term functional stability of isolated membrane proteins is crucial for many in vitro applications used to elucidate molecular mechanisms, and used for drug screening platforms in modern pharmaceutical industry. Compared to soluble proteins, the understanding at the molecular level of membrane proteins remains a challenge. This is partly due to the difficulty to isolate and simultaneously maintain their structural and functional stability, because of their hydrophobic nature. Here we show, how scintillation proximity assay can be used to analyze time-resolved high-affinity ligand binding to membrane proteins solubilized in various environments. The assay was used to establish conditions that preserved the biological function of isolated human kappa opioid receptor. In detergent solution the receptor lost high-affinity ligand binding to a radiolabelled ligand within minutes at room temperature. After reconstitution in Nanodiscs made of phospholipid bilayer the half-life of high-affinity ligand binding to the majority of receptors increased 70-fold compared to detergent solubilized receptors—a level of stability that is appropriate for further downstream applications. Time-resolved scintillation proximity assay has the potential to screen numerous conditions in parallel to obtain high levels of stable and active membrane proteins, which are intrinsically unstable in detergent solution, and with minimum material consumption. PMID:27035823

Bimanual Capacity of Children With Cerebral Palsy: Intra- and Interrater Reliability of a Revised Edition of the Bimanual Fine Motor Function Classification.

PubMed

Elvrum, Ann-Kristin G; Beckung, Eva; Sæther, Rannei; Lydersen, Stian; Vik, Torstein; Himmelmann, Kate

2017-08-01

To develop a revised edition of the Bimanual Fine Motor Function (BFMF 2), as a classification of fine motor capacity in children with cerebral palsy (CP), and establish intra- and interrater reliability of this edition. The content of the original BFMF was discussed by an expert panel, resulting in a revised edition comprising the original description of the classification levels, but in addition including figures with specific explanatory text. Four professionals classified fine motor function of 79 children (3-17 years; 45 boys) who represented all subtypes of CP and Manual Ability Classification levels (I-V). Intra- and inter-rater reliability was assessed using overall intra-class correlation coefficient (ICC), and Cohen's quadratic weighted kappa. The overall ICC was 0.86. Cohen's weighted kappa indicated high intra-rater (к w : >0.90) and inter-rater (к w : >0.85) reliability. The revised BFMF 2 had high intra- and interrater reliability. The classification levels could be determined from short video recordings (<5 minutes), using the figures and precise descriptions of the fine motor function levels included in the BFMF 2. Thus, the BFMF 2 may be a feasible and useful classification of fine motor capacity both in research and in clinical practice.

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

Wu, Huixian; Wacker, Daniel; Mileni, Mauro

Opioid receptors mediate the actions of endogenous and exogenous opioids on many physiological processes, including the regulation of pain, respiratory drive, mood, and - in the case of {kappa}-opioid receptor ({kappa}-OR) - dysphoria and psychotomimesis. Here we report the crystal structure of the human {kappa}-OR in complex with the selective antagonist JDTic, arranged in parallel dimers, at 2.9 {angstrom} resolution. The structure reveals important features of the ligand-binding pocket that contribute to the high affinity and subtype selectivity of JDTic for the human {kappa}-OR. Modelling of other important {kappa}-OR-selective ligands, including the morphinan-derived antagonists norbinaltorphimine and 5'-guanidinonaltrindole, and the diterpenemore » agonist salvinorin A analogue RB-64, reveals both common and distinct features for binding these diverse chemotypes. Analysis of site-directed mutagenesis and ligand structure-activity relationships confirms the interactions observed in the crystal structure, thereby providing a molecular explanation for {kappa}-OR subtype selectivity, and essential insights for the design of compounds with new pharmacological properties targeting the human {kappa}-OR.« less

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

[Study of functional rating scale for amyotrophic lateral sclerosis: revised ALSFRS(ALSFRS-R) Japanese version].

PubMed

Ohashi, Y; Tashiro, K; Itoyama, Y; Nakano, I; Sobue, G; Nakamura, S; Sumino, S; Yanagisawa, N

2001-04-01

Amyotrophic lateral sclerosis(ALS) is progressive, degenerative, fatal disease of the motor neuron. No efficacious therapy is available to slow the progressive loss of function, but several new approaches including neurotrophic factors, antioxidants and glutamate antagonists, are currently being evaluated as potential therapies. Mortality, and/or time to tracheostomy, muscle strength and pulmonary function are used as primary endpoints in clinical trials for treatment of ALS. The effect of new therapies on the quality of patients' lives are also important, so we sought to develop a rating scale to measure it. The revised ALS Functional Rating Scale(ALSFRS-R), which has addition of items to ALSFRS to enhance the ability to assess respiratory symptoms, is an assessment determining the degree of impairment in ALS patients' abilities to function independently in activities of daily living. It consists of 12 items to evaluate bulbar function, motor function and respiratory function and each item is scored from 0(unable) to 4(normal). We translated the English score into Japanese one with minor modification considering the inter cultural difference. And we examined reliability of the translated scale. As a measure of reliability, the intraclass correlation coefficient(ICC) was evaluated for total score and the Kappa coefficient proposed by Cohen and Kraemer was calculated for each item. Moreover, we examined sensitivity to clinical change over time and carried out the factor analysis to analyze the factorial structure. The subjects were 27 ALS patients and each was scored twice for reliability or three times for sensitivity by 2 to 5 neurologists and if possible, nurses. The ICC for total score was 0.97(95% C. I.; 0.94-0.98). Extension of the Kappa coefficients were 0.48 to 1.00 for inter-rater reliability and the averaged Kappa coefficients were 0.63 to 1.00 for intra rater reliability, respectively. Concerning the factorial structure, the contribution of the first factor(the first principal component) were 53.5% principal factor solution. The factor loadings of items were 0.52-0.91 except "salivation" and this factor almost equal to the simple sum of all items was interpreted as the general degree of deterioration. The promax votation revealed the riginally supposed factor structure with 3 factors(groups of items): neuromuscuclar function, respiratory function and bulbar function. The rating scale correlated with Global clinical impression of change(GCIC) scored by neurologists and declined with time, indicating its sensitivity to change. On the bases of these results, ALSFRS-R(Japanese version) is considered to be highly reliable enough for clinical use.

Incongruence between women's survey- and interview-determined decision control preferences: A mixed methods study of decision-making in metastatic breast cancer.

PubMed

Ejem, Deborah; Dionne-Odom, J Nicholas; Turkman, Yasemin; Knight, Sara J; Willis, Dan; Kaufman, Peter A; Bakitas, Marie

2018-04-30

Women with metastatic breast cancer face numerous, complex treatment and advance care planning (ACP) decisions. Our aim was to develop a better understanding of women with metastatic breast cancer's decision-making preferences overtime and relative to specific types of decisions. Convergent, parallel mixed-methods study. Participants completed the Control Preferences Scale (CPS) and a semi-structured interview of decision-making experiences at enrollment (T1; n = 22) and when facing a decision or 3 months later (T2; n = 19). We categorized women's decision-making experience descriptions into one of the CPS decisional styles and compared them to their CPS response. We constructed an analytic grid that aligned the interview-determined treatment and ACP decisional preferences with the CPS categories at T1 and T2 and calculated Cohen's kappa coefficient and congruence percentages. Participants (n = 22) were White (100%), averaged 62 years, married (54%), retired (45%), and had a bachelor's degree (45%). Congruence between CPS response and interview-determined treatment preferences at T1 was 32% (kappa = 0.083) and 33% (kappa = 0.120) at T2. Congruence between CPS survey response and interview-determined ACP preferences at T1 was 22.7% (kappa =0.092) at T1 and 11% (kappa = 0.011) at T2. Although women selected a "shared" treatment decision-making style using the CPS validated tool, when interviewed their descriptions generally reflected a passive process in which they followed the oncologists' treatment suggestions. Future research should explore whether the incongruence between stated and actual decision-making style is a function of misinterpreting the CPS choices or a true inconsistency that could lead to adverse consequences such as decisional regret. Copyright © 2018 John Wiley & Sons, Ltd.

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.

Analysis and Comparison of Extended and Unscented Kalman Filtering Methods for Spacecraft Attitude Determination

DTIC Science & Technology

2010-12-01

3)+m*l^2); fncC.m %# eml function y = fncC(x) Bo=0.5; alf=30*pi/180; y=Bo*sin(x(1,1)+alf); 75 Unscented Kalman Filter – Embedded...Matlab Block %# eml function [x_k1,Pxx_k1] = UKF(x_k,Pxx_k,Y_meas,ts,Q,R,kappa) % This block supports the Embedded MATLAB subset. % See the...torque2omegadot.m EML function Wdot = torque2omegadot(T, J, W) % This function takes input of applied torque (T) in component % elements, current angular

Accuracy of topographic index models at identifying ephemeral gully trajectories on agricultural fields

NASA Astrophysics Data System (ADS)

Sheshukov, Aleksey Y.; Sekaluvu, Lawrence; Hutchinson, Stacy L.

2018-04-01

Topographic index (TI) models have been widely used to predict trajectories and initiation points of ephemeral gullies (EGs) in agricultural landscapes. Prediction of EGs strongly relies on the selected value of critical TI threshold, and the accuracy depends on topographic features, agricultural management, and datasets of observed EGs. This study statistically evaluated the predictions by TI models in two paired watersheds in Central Kansas that had different levels of structural disturbances due to implemented conservation practices. Four TI models with sole dependency on topographic factors of slope, contributing area, and planform curvature were used in this study. The observed EGs were obtained by field reconnaissance and through the process of hydrological reconditioning of digital elevation models (DEMs). The Kernel Density Estimation analysis was used to evaluate TI distribution within a 10-m buffer of the observed EG trajectories. The EG occurrence within catchments was analyzed using kappa statistics of the error matrix approach, while the lengths of predicted EGs were compared with the observed dataset using the Nash-Sutcliffe Efficiency (NSE) statistics. The TI frequency analysis produced bi-modal distribution of topographic indexes with the pixels within the EG trajectory having a higher peak. The graphs of kappa and NSE versus critical TI threshold showed similar profile for all four TI models and both watersheds with the maximum value representing the best comparison with the observed data. The Compound Topographic Index (CTI) model presented the overall best accuracy with NSE of 0.55 and kappa of 0.32. The statistics for the disturbed watershed showed higher best critical TI threshold values than for the undisturbed watershed. Structural conservation practices implemented in the disturbed watershed reduced ephemeral channels in headwater catchments, thus producing less variability in catchments with EGs. The variation in critical thresholds for all TI models suggested that TI models tend to predict EG occurrence and length over a range of thresholds rather than find a single best value.

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.

A pro-inflammatory role of deubiquitinating enzyme cylindromatosis (CYLD) in vascular smooth muscle cells

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

Liu, Shuai; Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29208; Lv, Jiaju

2012-03-30

Highlights: Black-Right-Pointing-Pointer Cyld deficiency suppresses pro-inflammatory phenotypic switch of VSMCs. Black-Right-Pointing-Pointer Cyld deficiency inhibits MAPK rather than NF-kB activity in inflamed VSMCs. Black-Right-Pointing-Pointer CYLD is up-regulated in the coronary artery with neointimal hyperplasia. -- Abstract: CYLD, a deubiquitinating enzyme (DUB), is a critical regulator of diverse cellular processes, ranging from proliferation and differentiation to inflammatory responses, via regulating multiple key signaling cascades such as nuclear factor kappa B (NF-{kappa}B) pathway. CYLD has been shown to inhibit vascular lesion formation presumably through suppressing NF-{kappa}B activity in vascular cells. However, herein we report a novel role of CYLD in mediating pro-inflammatory responsesmore » in vascular smooth muscle cells (VSMCs) via a mechanism independent of NF-{kappa}B activity. Adenoviral knockdown of Cyld inhibited basal and the tumor necrosis factor alpha (TNF{alpha})-induced mRNA expression of pro-inflammatory cytokines including monocyte chemotactic protein-1 (Mcp-1), intercellular adhesion molecule (Icam-1) and interleukin-6 (Il-6) in rat adult aortic SMCs (RASMCs). The CYLD deficiency led to increases in the basal NF-{kappa}B transcriptional activity in RASMCs; however, did not affect the TNF{alpha}-induced NF-{kappa}B activity. Intriguingly, the TNF{alpha}-induced I{kappa}B phosphorylation was enhanced in the CYLD deficient RASMCs. While knocking down of Cyld decreased slightly the basal expression levels of I{kappa}B{alpha} and I{kappa}B{beta} proteins, it did not alter the kinetics of TNF{alpha}-induced I{kappa}B protein degradation in RASMCs. These results indicate that CYLD suppresses the basal NF-{kappa}B activity and TNF{alpha}-induced I{kappa}B kinase activation without affecting TNF{alpha}-induced NF-{kappa}B activity in VSMCs. In addition, knocking down of Cyld suppressed TNF{alpha}-induced activation of mitogen activated protein kinases (MAPKs) including extracellular signal-activated kinases (ERK), c-Jun N-terminal kinase (JNK), and p38 in RASMCs. TNF{alpha}-induced RASMC migration and monocyte adhesion to RASMCs were inhibited by the Cyld knockdown. Finally, immunochemical staining revealed a dramatic augment of CYLD expression in the injured coronary artery with neointimal hyperplasia. Taken together, our results uncover an unexpected role of CYLD in promoting inflammatory responses in VSMCs via a mechanism involving MAPK activation but independent of NF-{kappa}B activity, contributing to the pathogenesis of vascular disease.« less

Nuclear factor-kappaB activation and postischemic inflammation are suppressed in CD36-null mice after middle cerebral artery occlusion.

PubMed

Kunz, Alexander; Abe, Takato; Hochrainer, Karin; Shimamura, Munehisa; Anrather, Josef; Racchumi, Gianfranco; Zhou, Ping; Iadecola, Costantino

2008-02-13

CD36, a class-B scavenger receptor involved in multiple functions, including inflammatory signaling, may also contribute to ischemic brain injury through yet unidentified mechanisms. We investigated whether CD36 participates in the molecular events underlying the inflammatory reaction that accompanies cerebral ischemia and may contribute to the tissue damage. We found that activation of nuclear factor-kappaB, a transcription factor that coordinates postischemic gene expression, is attenuated in CD36-null mice subjected to middle cerebral artery occlusion. The infiltration of neutrophils and the glial reaction induced by cerebral ischemia were suppressed. Treatment with an inhibitor of inducible nitric oxide synthase, an enzyme that contributes to the tissue damage, reduced ischemic brain injury in wild-type mice, but not in CD36 nulls. In contrast to cerebral ischemia, the molecular and cellular inflammatory changes induced by intracerebroventricular injection of interleukin-1beta were not attenuated in CD36-null mice. The findings unveil a novel role of CD36 in early molecular events leading to nuclear factor-kappaB activation and postischemic inflammation. Inhibition of CD36 signaling may be a valuable therapeutic approach to counteract the deleterious effects of postischemic inflammation.

Diploidy and the selective advantage for sexual reproduction in unicellular organisms.

PubMed

Kleiman, Maya; Tannenbaum, Emmanuel

2009-11-01

This article develops mathematical models describing the evolutionary dynamics of both asexually and sexually reproducing populations of diploid unicellular organisms. The asexual and sexual life cycles are based on the asexual and sexual life cycles in Saccharomyces cerevisiae, Baker's yeast, which normally reproduces by asexual budding, but switches to sexual reproduction when stressed. The mathematical models consider three reproduction pathways: (1) Asexual reproduction, (2) self-fertilization, and (3) sexual reproduction. We also consider two forms of genome organization. In the first case, we assume that the genome consists of two multi-gene chromosomes, whereas in the second case, we consider the opposite extreme and assume that each gene defines a separate chromosome, which we call the multi-chromosome genome. These two cases are considered to explore the role that recombination has on the mutation-selection balance and the selective advantage of the various reproduction strategies. We assume that the purpose of diploidy is to provide redundancy, so that damage to a gene may be repaired using the other, presumably undamaged copy (a process known as homologous recombination repair). As a result, we assume that the fitness of the organism only depends on the number of homologous gene pairs that contain at least one functional copy of a given gene. If the organism has at least one functional copy of every gene in the genome, we assume a fitness of 1. In general, if the organism has l homologous pairs that lack a functional copy of the given gene, then the fitness of the organism is kappa(l). The kappa(l) are assumed to be monotonically decreasing, so that kappa(0) = 1 > kappa(1) > kappa(2) > cdots, three dots, centered > kappa(infinity) = 0. For nearly all of the reproduction strategies we consider, we find, in the limit of large N, that the mean fitness at mutation-selection balance is max{2e(-mu) - 1,0} where N is the number of genes in the haploid set of the genome, epsilon is the probability that a given DNA template strand of a given gene produces a mutated daughter during replication, and mu = Nepsilon. The only exception is the sexual reproduction pathway for the multi-chromosomed genome. Assuming a multiplicative fitness landscape where kappa(l) = alpha(l) for alpha in (0, 1), this strategy is found to have a mean fitness that exceeds the mean fitness of all the other strategies. Furthermore, while other reproduction strategies experience a total loss of viability due to the steady accumulation of deleterious mutations once mu exceeds [Formula: see text] no such transition occurs in the sexual pathway. Indeed, in the limit as alpha --> 1 for the multiplicative landscape, we can show that the mean fitness for the sexual pathway with the multi-chromosomed genome converges to e(-2mu), which is always positive. We explicitly allow for mitotic recombination in this study, which, in contrast to previous studies using different models, does not have any advantage over other asexual reproduction strategies. The results of this article provide a basis for understanding the selective advantage of the specific meiotic pathway that is employed by sexually reproducing organisms. The results of this article also suggest an explanation for why unicellular organisms such as Saccharomyces cerevisiae (Baker's yeast) switch to a sexual mode of reproduction when stressed. While the results of this article are based on modeling mutation-propagation in unicellular organisms, they nevertheless suggest that, in more complex organisms with significantly larger genomes, sex is necessary to prevent the loss of viability of a population due to genetic drift. Finally, and perhaps most importantly, the results of this article demonstrate a selective advantage for sexual reproduction with fewer and much less restrictive assumptions than those of previous studies.

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

Sundar, Isaac K.; Hwang, Jae-Woong; Wu, Shaoping

Research highlights: {yields} Vitamin D deficiency is linked to accelerated decline in lung function. {yields} Levels of vitamin D receptor (VDR) are decreased in lungs of patients with COPD. {yields} VDR knock-out mouse showed increased lung inflammation and emphysema. {yields} This was associated with decline in lung function and increased MMPs. {yields} VDR knock-out mouse model is useful for studying the mechanisms of lung diseases. -- Abstract: Deficiency of vitamin D is associated with accelerated decline in lung function. Vitamin D is a ligand for nuclear hormone vitamin D receptor (VDR), and upon binding it modulates various cellular functions. Themore » level of VDR is reduced in lungs of patients with chronic obstructive pulmonary disease (COPD) which led us to hypothesize that deficiency of VDR leads to significant alterations in lung phenotype that are characteristics of COPD/emphysema associated with increased inflammatory response. We found that VDR knock-out (VDR{sup -/-}) mice had increased influx of inflammatory cells, phospho-acetylation of nuclear factor-kappaB (NF-{kappa}B) associated with increased proinflammatory mediators, and up-regulation of matrix metalloproteinases (MMPs) MMP-2, MMP-9, and MMP-12 in the lung. This was associated with emphysema and decline in lung function associated with lymphoid aggregates formation compared to WT mice. These findings suggest that deficiency of VDR in mouse lung can lead to an early onset of emphysema/COPD because of chronic inflammation, immune dysregulation, and lung destruction.« less

Ecologically relevant outcome measure for post-inpatient rehabilitation.

PubMed

Marquez de la Plata, Carlos; Qualls, Devin; Plenger, Patrick; Malec, James F; Hayden, Mary Ellen

2017-01-01

Transfer of skills learned within the clinic environment to patients' home or community is important in post-inpatient brain injury rehabilitation (PBIR). Outcome measures used in PBIR assess level of independence during functional tasks; however, available functional instruments do not quantitate the environment in which the behaviors occur. To examine the reliability and validity of an instrument used to assess patients' functional abilities while quantifying the amount of structure and distractions in the environment. 2501 patients who sustained a traumatic brain injury (TBI) or cerebrovascular accident (CVA) and participated in a multidisciplinary PBIR program between 2006 and 2014 were identified retrospectively for this study. The PERPOS and MPAI-4 were used to assess functional abilities at admission and at discharge. Construct validity was assessed using a bivariate Spearman rho analysis A subsample of 56 consecutive admissions during 2014 were examined to determine inter-rater reliability. Intra-class correlation coefficient (ICC) and Kappa coefficients assessed inter-rater agreement of the total PERPOS and PERPOS subscales respectively. The PERPOS and MPAI-4 demonstrated a strong negative association among both TBI and CVA patients. Kappa scores for the three PERPOS scales each demonstrated good to excellent inter-rater agreement. The ICC for overall PERPOS scores fell in the good agreement range. The PERPOS can be used reliably in PBIR to quantify patients' functional abilities within the context of environmental demands.

The consistency of antibiotic resistance' results in two methods of disk diffusion and MIC in isolated organisms from patients with urinary tract infections.

PubMed

Karami, A; Mazloom Zadeh, S; Rastin, A; Karami, A; Shiri, P

2015-01-01

Introduction: The urinary tract infection is the most common infection and drug resistance to it is increasing. Due to the acute infection, the prescribing of medicine is conducted before culture and antibiogram and according to the results, disk diffusion is adjusted. The aim of this study was to compare it with MIC to determine to what extent the current method could be useful. Methods: This descriptive cross-sectional investigation research regarding drug resistance was conducted with the help of two methods of disk diffusion and MIC on the isolations of patients' urine culture with UTI (midstream clean catch). Bacterial resistance was measured, and sensitivity and specificity were evaluated. Results: The MIC method was considered the gold standard and, according to the related formula, the sensitivity and specificity of disk diffusion were related to 13 antibiotics obtained as it follows: ciprofloxacin 69% and 69.1% (0.0001 > p and Kappa = .292), cotrimoxazole 50% and 77.3% (p = 0.010), nitrofurantoin 84.7% and 58.2% (0.0001 > p and Kappa = 0.44), ampicilin 83.3% and 85.3% (0.0001 > p and Kappa = 0.33), ofloxacin 65.5% and 83.9% (0.0001 > p and Kappa = 0.429), cephalexin 46.2% and 75.2% (p = 0.012 and Kappa = 0.116), gentamicin 64.2% and 66% (0.0001 > p and Kappa = 0.276), ceftriaxone 27.6% and 80.9% (p = 0.216 and Kappa = 0.074), nalidixic acid 42.1% and 89.2% (0.0001 > p and Kappa = 0.354), imipenem 63.4% and 70.4% (0.0001 > p and Kappa 0.306), co-amoxiclav 83% and 71% (0.0001 > p and Kappa = 0.412), cefixime 21% and 80.9% (0.0001 > p and Kappa = 0.412), vancomycin 55.9% and 94.7 (0.9001 > p and Kappa = 0.532). Sensitivity and specificity of this method were reported to be lower than MIC. Conclusions: Due to the low sensitivity and specificity of the disk diffusion method, antibiotic therapy should be certainly considered in clinical conditions, and risk factors for the infection and only by this approach cannot prescribe the drug.

Comparison of intra-oral and study cast measurements in the assessment of malocclusion.

PubMed

Ovsenik, Maja; Farcnik, Franc M; Verdenik, Ivan

2004-06-01

Malocclusion assessment methods are based on registrations and measurements made on study casts, which requires that impressions be taken. In addition to being costly and time-consuming, this process can be unpleasant for very young children. Therefore, the aim of this study was to evaluate the reliability of intra-oral measurements that compute a malocclusion index score to determine malocclusion severity in the mixed dentition. The research was part of a longitudinal study in Slovenia on a sample of 530 3-year-old children. At 8 years of age (mean 8.5 years, standard deviation 0.2), a cohort of 101 children (44 boys, 57 girls) was randomly selected in a cross-sectional study. Quantitative registrations of space and occlusal anomalies were performed intra-orally as well as on study casts. Kappa (kappa) statistics were used to evaluate the agreement between clinical and study cast malocclusion assessments. Systematic bias of measurements was tested using Wilcoxon's signed rank test. The results showed complete agreement between the two measurements for anterior crossbite, anterior open bite and overjet scores (kappa = 1); excellent reliability for the buccal segment relationship (kappa = 0.93), transverse occlusion of posterior teeth (kappa = 0.87); and substantial agreement for overbite (kappa = 0.79) and midline deviation (kappa = 0.71). For the remainder of the traits the agreement was moderate: rotation of incisors (kappa = 0.58), crowding of upper incisors (kappa = 0.51), axial inclination of teeth (kappa = 0.44) and lower incisor crowding (kappa = 0.41). Intra-orally small, but statistically significant scoring of lower incisor rotation and crowding was identified. On the study casts the most favourable axial inclination was found for buccal segment occlusion. Overall classification into severity grades, based on the total malocclusion score, showed excellent agreement between the two methods (kappa = 0.89), without statistically significant bias. Malocclusion assessment, recorded and measured intra-orally, is as reliable as assessment on study casts. The proposed method can be used in screening, in epidemiological studies and in clinical orthodontic assessment.

The Systemic Sclerosis Questionnaire (SySQ): Validation of the translation of the original German version into Spanish and its relationship to the disease and to quality of life.

PubMed

Cruz-Domínguez, Maria Pilar; Casarrubias-Ramírez, Moisés; Gasca-Martínez, Victor; Maldonado García, Cindy; Carranza-Muleiro, Rosa Angélica; Medina, Gabriela; García-Collinot, Grettel; Montes-Cortes, Daniel Hector

2017-12-11

Translation, transculturation and validity of the self-administered questionnaire for functionality (Systemic Sclerosis Questionnaires [SySQ]) for use in Spanish patients with systemic sclerosis and its relationship to the severity of the disease and to quality of life. We conducted an observational analytical study to perform a cross-cultural validation of the self-administered questionnaire on functionality in scleroderma. The validity of the form and content was evaluated by an expert panel. The method included: a) adaptation into Spanish of the construct for translation and back translation, and transculturation; b) internal consistency with the SySQ (Cronbach's alpha), and c) reproducibility was assessed taking into account all occasions in which the test was performed with Cohen's kappa. Additionally, we calculated the Spearman correlation coefficient with the Medsger severity scale, Health Assessment Questionnaire score and SF-36 score. We included 70 patients with systemic sclerosis: age 17-78 (51±12) years, 65 (93%) were women, diffuse/limited subtype 64/36%, disease duration of 0.5-40 years. Optimal internal consistency for all categories of the final version of SySQ (Cronbach's α of 0.961) and intraobserver reliability in 2 tests over a 2-week interval (Cohen's kappa coefficient 0.618) and optimal interobserver reliability in 2 tests on the same day (Cohen's kappa coefficient 0.911). Moderate correlation between functionality by SySQ and by Health Assessment Questionnaire (r=0.573, P<.0001). Inverse correlation between SySQ and quality of life mental health domain SF-36 (r=-0.435, P<.001) and physical domain SF-36 (r=-0.638, P<.001). Medsger severity scale (tendon, heart, lung, vascular) also showed significant correlation with SySQ. SySQ in this validated Spanish version is a suitable instrument to measure functional status in patients with systemic sclerosis. Reduced functionality is related to greater tendon and peripheral vascular involvement and to a poorer quality of life. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

The value of specific MRI features in the evaluation of suspected placental invasion.

PubMed

Lax, Allison; Prince, Martin R; Mennitt, Kevin W; Schwebach, J Reid; Budorick, Nancy E

2007-01-01

The objective of this study was to determine imaging features that may help predict the presence of placenta accreta, placenta increta or placenta percreta on prenatal MRI scanning. A retrospective review of the prenatal MR scans of 10 patients with a diagnosis of placenta accreta, placenta increta or placenta percreta made by pathologic and clinical reports and of 10 patients without placental invasion was performed. Two expert MRI readers were blinded to the patients' true diagnosis and were asked to score a total of 17 MRI features of the placenta and adjacent structures. The interrater reliability was assessed using kappa statistics. The features with a moderate kappa statistic or better (kappa > .40) were then compared with the true diagnosis for each observer. Seven of the scored features had an interobserver reliability of kappa > .40: placenta previa (kappa = .83); abnormal uterine bulging (kappa = .48); intraplacental hemorrhage (kappa = .51); heterogeneity of signal intensity on T2-weighted (T2W) imaging (kappa = .61); the presence of dark intraplacental bands on T2W imaging (kappa = .53); increased placental thickness (kappa = .69); and visualization of the myometrium beneath the placenta on T2W imaging (kappa = .44). Using Fisher's two-sided exact test, there was a statistically significant difference between the proportion of patients with placental invasion and those without placental invasion for three of the features: abnormal uterine bulging (Rater 1, P = .005; Rater 2, P = .011); heterogeneity of T2W imaging signal intensity (Rater 1, P = .006; Rater 2, P = .010); and presence of dark intraplacental bands on T2W imaging (Rater 1, P = .003; Rater 2, P = .033). MRI can be a useful adjunct to ultrasound in diagnosing placenta accreta prenatally. Three features that are seen on MRI in patients with placental invasion appear to be useful for diagnosis: uterine bulging; heterogeneous signal intensity within the placenta; and the presence of dark intraplacental bands on T2W imaging.

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

Huang, Chien-Sheng; Division of Thoracic Surgery, Department of Surgery, Taipei-Veterans General Hospital and National Yang-Ming University School of Medicine, Taipei, Taiwan; Kawamura, Tomohiro

Highlights: {yields} Hydrogen is a regulatory molecule with antiinflammatory and antiapoptotic protective effects. {yields} There is very limited information on the pathways regulated in vivo by the hydrogen. {yields} Antiapoptotic abilities of hydrogen were explained by upregulation of the antiapoptotic gene. {yields} NF{kappa}B activation during hydrogen treatment was correlated with elevated antiapoptotic protein. {yields} NF{kappa}B activation associated with increase Bcl-2 may contribute to cytoprotection of hydrogen. -- Abstract: We recently demonstrated the inhalation of hydrogen gas, a novel medical therapeutic gas, ameliorates ventilator-induced lung injury (VILI); however, the molecular mechanisms by which hydrogen ameliorates VILI remain unclear. Therefore, we investigatedmore » whether inhaled hydrogen gas modulates the nuclear factor-kappa B (NF{kappa}B) signaling pathway. VILI was generated in male C57BL6 mice by performing a tracheostomy and placing the mice on a mechanical ventilator (tidal volume of 30 ml/kg or 10 ml/kg without positive end-expiratory pressure). The ventilator delivered either 2% nitrogen or 2% hydrogen in balanced air. NF{kappa}B activation, as indicated by NF{kappa}B DNA binding, was detected by electrophoretic mobility shift assays and enzyme-linked immunosorbent assay. Hydrogen gas inhalation increased NF{kappa}B DNA binding after 1 h of ventilation and decreased NF{kappa}B DNA binding after 2 h of ventilation, as compared with controls. The early activation of NF{kappa}B during hydrogen treatment was correlated with elevated levels of the antiapoptotic protein Bcl-2 and decreased levels of Bax. Hydrogen inhalation increased oxygen tension, decreased lung edema, and decreased the expression of proinflammatory mediators. Chemical inhibition of early NF{kappa}B activation using SN50 reversed these protective effects. NF{kappa}B activation and an associated increase in the expression of Bcl-2 may contribute, in part, to the cytoprotective effects of hydrogen against apoptotic and inflammatory signaling pathway activation during VILI.« less

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.

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

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

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.

6-Shogaol suppressed lipopolysaccharide-induced up-expression of iNOS and COX-2 in murine macrophages.

PubMed

Pan, Min-Hsiung; Hsieh, Min-Chi; Hsu, Ping-Chi; Ho, Sheng-Yow; Lai, Ching-Shu; Wu, Hou; Sang, Shengmin; Ho, Chi-Tang

2008-12-01

Ginger, the rhizome of Zingiber officinale, is a traditional medicine with carminative effect, antinausea, anti-inflammatory, and anticarcinogenic properties. In this study, we investigated the inhibitory effects of 6-shogaol and a related compound, 6-gingerol, on the induction of nitric oxide synthase (NOS) and cyclooxygenase-2 (COX-2) in murine RAW 264.7 cells activated with LPS. Western blotting and reverse transcription-PCR analyses demonstrated that 6-shogaol significantly blocked protein and mRNA expression of inducible NOS (iNOS) and COX-2 in LPS-induced macrophages. The in vivo anti-inflammatory activity was evaluated by a topical 12-O-tetradecanoylphorbol 13-acetate (TPA) application to mouse skin. When applied topically onto the shaven backs of mice prior to TPA, 6-shogaol markedly inhibited the expression of iNOS and COX-2 proteins. Treatment with 6-shogaol resulted in the reduction of LPS-induced nuclear translocation of nuclear factor-kappaB (NF kappaB) subunit and the dependent transcriptional activity of NF kappaB by blocking phosphorylation of inhibitor kappaB (I kappaB)alpha and p65 and subsequent degradation of I kappaB alpha. Transient transfection experiments using NF kappaB reporter constructs indicated that 6-shogaol inhibits the transcriptional activity of NF kappaB in LPS-stimulated mouse macrophages. We found that 6-shogaol also inhibited LPS-induced activation of PI3K/Akt and extracellular signal-regulated kinase 1/2, but not p38 mitogen-activated protein kinase (MAPK). Taken together, these results show that 6-shogaol downregulates inflammatory iNOS and COX-2 gene expression in macrophages by inhibiting the activation of NF kappaB by interfering with the activation PI3K/Akt/I kappaB kinases IKK and MAPK.

miR-218 inhibits the invasive ability of glioma cells by direct downregulation of IKK-{beta}

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

Song, Libing, E-mail: lb.song1@gmail.com; Huang, Quan; Chen, Kun

2010-11-05

Research highlights: {yields} miR-218 is markedly downregulated in glioma cell lines and in primary glioma tissues. {yields} Upregulation of miR-218 dramatically reduces the invasive ability of glioma cells. {yields} Ectopic expression of miR-218 inactivates IKK-{beta}/NF-{kappa}B signaling pathway. {yields} miR-218 directly targets the 3'-untranslated region (3'-UTR) of IKK-{beta}. -- Abstract: Aberrant activation of nuclear factor-kappa B (NF-{kappa}B) pathway has been proven to play important roles in the development and progression of cancers. Activation of NF-{kappa}B via the classical pathway is modulated by I{kappa}Bs kinase (IKK-{beta}). However, the mechanism underlying the epigenetic regulation of IKK-{beta}/NF-{kappa}B pathway remains largely unknown. In this study,more » we found that the expression level of miR-218 was markedly downregulated in glioma cell lines and in human primary glioma tissues. Upregulation of miR-218 dramatically reduced the migratory speed and invasive ability of glioma cells. Furthermore, we showed that ectopically expressing miR-218 in glioma cells resulted in downregulation of matrix metalloproteinase-9 (MMP-9) and reduction in NF-{kappa}B transactivity at a transcriptional level, but inhibition of miR-218 enhanced the expression of MMP-9 and transcriptional activity of NF-{kappa}B. Moreover, we showed that miR-218 inactivated the NF-{kappa}B pathway through downregulating IKK-{beta} expression by directly targeting the 3'-untranslated region (3'-UTR) of IKK-{beta}. Taken together, our results suggest that miR-218 plays an important role in preventing the invasiveness of glioma cells, and our results present a novel mechanism of miRNA-mediated direct suppression of IKK-{beta}/NF-{kappa}B pathway in gliomas.« less

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

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.

Liquid-liquid extraction of ethanol from aqueous solutions with amyl acetate, benzyl alcohol, and methyl isobutyl ketone at 298. 15. Kappa

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

Solimo, H.N.; Martinez, H.E.; Riggio, R.

1989-04-01

Experimental mutual solubility and tie-line data were determined for three ternary liquid-liquid systems containing water, ethanol, and amyl acetate, benzyl alcohol, and methyl isobutyl ketone at 298.15{Kappa} in order to obtain their complete phase diagrams and to determine which is the most suitable solvent for extraction of ethanol from aqueous solutions. Tie lines were determined correlating the density of the binodal curve as a function of composition and the plait points using the Othmer and Tobias method. The experimental data were also correlated with the UNIFAC group contribution method. A qualitative agreement was obtained. Experimental results show that amyl acetatemore » is a better solvent than methyl isobutyl ketone and benzyl alcohol.« less

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

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.

An analysis of supersonic flows with low-Reynolds number compressible two-equation turbulence models using LU finite volume implicit numerical techniques

NASA Technical Reports Server (NTRS)

Lee, J.

1994-01-01

A generalized flow solver using an implicit Lower-upper (LU) diagonal decomposition based numerical technique has been coupled with three low-Reynolds number kappa-epsilon models for analysis of problems with engineering applications. The feasibility of using the LU technique to obtain efficient solutions to supersonic problems using the kappa-epsilon model has been demonstrated. The flow solver is then used to explore limitations and convergence characteristics of several popular two equation turbulence models. Several changes to the LU solver have been made to improve the efficiency of turbulent flow predictions. In general, the low-Reynolds number kappa-epsilon models are easier to implement than the models with wall-functions, but require much finer near-wall grid to accurately resolve the physics. The three kappa-epsilon models use different approaches to characterize the near wall regions of the flow. Therefore, the limitations imposed by the near wall characteristics have been carefully resolved. The convergence characteristics of a particular model using a given numerical technique are also an important, but most often overlooked, aspect of turbulence model predictions. It is found that some convergence characteristics could be sacrificed for more accurate near-wall prediction. However, even this gain in accuracy is not sufficient to model the effects of an external pressure gradient imposed by a shock-wave/ boundary-layer interaction. Additional work on turbulence models, especially for compressibility, is required since the solutions obtained with base line turbulence are in only reasonable agreement with the experimental data for the viscous interaction problems.

Effects of resveratrol-related hydroxystilbenes on the nitric oxide production in macrophage cells: structural requirements and mechanism of action.

PubMed

Cho, Dong-Im; Koo, Na-Youn; Chung, Woon Jae; Kim, Tae-Sung; Ryu, Shi Yong; Im, Suhn Young; Kim, Kyeong-Man

2002-09-13

NF-kappaB that plays an important role in iNOS expression is one of the targets of various potential anti-inflammatory agents including resveratrol. Resveratrol contains a structural similarity with estrogen, and there has been speculation about resveratrol as estrogen agonist. In this study, the mechanism and structural requirements of resveratrol and related hydroxystilbenes for the inhibition of LPS-induced nitric oxide production were studied in macrophage cells (RAW 264.7 and J774) by comparing its effect on LPS-induced NF-kappaB translocation and nitric oxide production, and by considering the possibility of involvement of an estrogen receptor. LPS-induced nitric oxide production was inhibited only when cells were treated with resveratrol prior to stimulation with LPS, suggesting that resveratrol does not affect the enzyme itself. A higher concentration of resveratrol than needed for the inhibition of nitric oxide production was required for the inhibition of NF-kappaB mobilization or iNOS expression. Estrogen and diethylstilbesterol, an estrogen agonist, caused only weak inhibition of nitric oxide production, and the effects of resveratrol were not noticeably blocked by ICI-182780, an estrogen antagonist. Structure-activity analysis of resveratrol and nine hydroxystilbenes suggests that the structural balance between oxygen functional groups on the benzene rings is important for their activity. Our results suggest that resveratrol might act on other cellular targets as well as NF-kappaB at the initial stage of gene expression. Unique structural features of hydroxystilbenes are needed for suppression of nitric oxide production and it is unlikely that estrogen receptor is involved in it.

Delphinidin, a specific inhibitor of histone acetyltransferase, suppresses inflammatory signaling via prevention of NF-{kappa}B acetylation in fibroblast-like synoviocyte MH7A cells

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

Seong, Ah-Reum; Yoo, Jung-Yoon; Choi, KyungChul

Highlights: {yields} Delphinidin is a novel inhibitor of p300/CBP histone acetyltransferase. {yields} Delphinidin prevents the hyperacetylation of p65 by inhibiting the HAT activity of p300/CBP. {yields} Delphinidin efficiently suppresses the expression of inflammatory cytokines in MH7A cells via hypoacetylation of NF-{kappa}B. {yields} Delphinidin inhibits cytokine release in the Jurkat T lymphocyte cell line. -- Abstract: Histone acetyltransferase (HAT) inhibitors (HATi) isolated from dietary compounds have been shown to suppress inflammatory signaling, which contributes to rheumatoid arthritis. Here, we identified a novel HATi in Punica granatum L. known as delphinidin (DP). DP did not affect the activity of other epigenetic enzymesmore » (histone deacetylase, histone methyltransferase, or sirtuin1). DP specifically inhibited the HAT activities of p300/CBP. It also inhibited p65 acetylation in MH7A cells, a human rheumatoid arthritis synovial cell line. DP-induced hypoacetylation was accompanied by cytosolic accumulation of p65 and nuclear localization of IKB{alpha}. Accordingly, DP treatment inhibited TNF{alpha}-stimulated increases in NF-{kappa}B function and expression of NF-{kappa}B target genes in these cells. Importantly, DP suppressed lipopolysaccharide-induced pro-inflammatory cytokine expression in Jurkat T lymphocytes, demonstrating that HATi efficiently suppresses cytokine-mediated immune responses. Together, these results show that the HATi activity of DP counters anti-inflammatory signaling by blocking p65 acetylation and that this compound may be useful in preventing inflammatory arthritis.« less

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.

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

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.

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.

Knowledge of the pelvic floor in nulliparous women

PubMed Central

Neels, Hedwig; Wyndaele, Jean-Jacques; Tjalma, Wiebren A. A.; De Wachter, Stefan; Wyndaele, Michel; Vermandel, Alexandra

2016-01-01

[Purpose] Proper pelvic floor function is important to avoid serious dysfunctions including incontinence, prolapse, and sexual problems. The current study evaluated the knowledge of young nulliparous women about their pelvic floor and identified what additional information they wanted. [Subjects and Methods] In this cross-sectional survey, a validated, 36 item questionnaire was distributed to 212 nulliparous women. The questionnaire addressed demography, pelvic floor muscles, pelvic floor dysfunction, and possible information sources. Descriptive statistics were generated for all variables. Stability and validity testing were performed using Kappa statistics and intra class correlation coefficients to define agreement for each question. The study was approved by the ethics Committee (B300201318334). [Results] Using a VAS scale (0 to 10), the women rated their knowledge about the pelvic floor as a mean of 2.4 (SD 2.01). A total of 93% of the women were insufficiently informed and requested more information; 25% had concerns about developing urinary incontinence, and 14% about fecal incontinence. Many of the women were unaware what pelvic floor training meant. [Conclusion] There was a significant lack of knowledge about pelvic floor function among nulliparous women. The majority of nulliparous women expressed a need for education, which might offer a way to reduce dysfunction. PMID:27313364

Kadomtsev-Petviashvili solitons propagation in a plasma system with superthermal and weakly relativistic effects

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

Hafeez-Ur-Rehman; Mahmood, S.; Department of Physics and Applied Mathematics, PIEAS, Nilore, 44000 Islamabad

2011-12-15

Two dimensional (2D) solitons are studied in a plasma system comprising of relativistically streaming ions, kappa distributed electrons, and positrons. Kadomtsev-Petviashvili (KP) equation is derived through the reductive perturbation technique. Analytical solution of the KP equation has been studied numerically and graphically. It is noticed that kappa parameters of electrons and positrons as well as the ions relativistic streaming factor have an emphatic influence on the structural as well as propagation characteristics of two dimensional solitons in the considered plasma system. Our results may be helpful in the understanding of soliton propagation in astrophysical and laboratory plasmas, specifically the interactionmore » of pulsar relativistic wind with supernova ejecta and the transfer of energy to plasma by intense electric field of laser beams producing highly energetic superthermal and relativistic particles [L. Arons, Astrophys. Space Sci. Lib. 357, 373 (2009); P. Blasi and E. Amato, Astrophys. Space Sci. Proc. 2011, 623; and A. Shah and R. Saeed, Plasma Phys. Controlled Fusion 53, 095006 (2011)].« less

Assessment of left ventricular ejection fraction using an ultrasonic stethoscope in critically ill patients

PubMed Central

2012-01-01

Introduction Assessment of cardiac function is key in the management of intensive care unit (ICU) patients and frequently relies on the use of standard transthoracic echocardiography (TTE). A commercially available new generation ultrasound system with two-dimensional imaging capability, which has roughly the size of a mobile phone, is adequately suited to extend the physical examination. The primary endpoint of this study was to evaluate the additional value of this new miniaturized device used as an ultrasonic stethoscope (US) for the determination of left ventricular (LV) systolic function, when compared to conventional clinical assessment by experienced intensivists. The secondary endpoint was to validate the US against TTE for the semi-quantitative assessment of left ventricular ejection fraction (LVEF) in ICU patients. Methods In this single-center prospective descriptive study, LVEF was independently assessed clinically by the attending physician and echocardiographically by two experienced intensivists trained in critical care echocardiography who used the US (size: 135 × 73 × 28 mm; weight: 390 g) and TTE. LVEF was visually estimated semi-quantitatively and classified in one of the following categories: increased (LVEF > 75%), normal (LVEF: 50 to 75%), moderately reduced (LVEF: 30 to 49%), or severely reduced (LVEF < 30%). Biplane LVEF measured using the Simpson's rule on TTE loops by an independent investigator was used as reference. Results A total of 94 consecutive patients were studied (age: 60 ± 17 years; simplified acute physiologic score 2: 41 ± 15), 63 being mechanically ventilated and 36 receiving vasopressors and/or inotropes. Diagnostic concordance between the clinically estimated LVEF and biplane LVEF was poor (Kappa: 0.33; 95% CI: 0.16 to 0.49) and only slightly improved by the knowledge of a previously determined LVEF value (Kappa: 0.44; 95% CI: 0.22 to 0.66). In contrast, the diagnostic agreement was good between visually assessed LVEF using the US and TTE (Kappa: 0.75; CI 95%: 0.63 to 0.87) and between LVEF assessed on-line and biplane LVEF, regardless of the system used (Kappa: 0.75; CI 95%: 0.64 to 0.87 and Kappa: 0.70; CI 95%: 0.59 to 0.82, respectively). Conclusions In ICU patients, the extension of physical examination using an US improves the ability of trained intensivists to determine LVEF at bedside. With trained operators, the semi-quantitative assessment of LVEF using the US is accurate when compared to standard TTE. PMID:22335818

Genetics Home Reference: familial cylindromatosis

MedlinePlus

... instructions for making a protein that helps regulate nuclear factor-kappa-B. Nuclear factor-kappa-B is a group of related ... to certain signals. In regulating the action of nuclear factor-kappa-B, the CYLD protein allows cells ...

Angiotensin II and the transcription factor Rel/NF-kappaB link environmental water shortage with memory improvement.

PubMed

Frenkel, L; Freudenthal, R; Romano, A; Nahmod, V E; Maldonado, H; Delorenzi, A

2002-01-01

One of the essential requirements even in the most ancient life forms is to be able to preserve body fluid medium. In line with such requirement, animals need to perform different behaviors to cope with water shortages. As angiotensin II (ANGII) is involved on a widespread range of functions in vertebrates, including memory modulation, an integrative role, in response to an environmental water shortage, has been envisioned. Previous work on the semi-terrestrial and brackish-water crab Chasmagnathus granulatus showed that endogenous ANGII enhanced an associative long-term memory and, in addition, that high salinity environment induces both an increase of brain ANGII levels and memory improvement. Here, we show that in the crab Chasmagnathus air exposure transiently increases blood sodium concentration, significantly increases brain ANGII immunoreactivity, and has a facilitatory effect on memory that is abolished by a non-selective ANGII receptor antagonist, saralasin. Furthermore, Rel/NF-kappaB, a transcription factor activated by ANGII in mammals and during memory consolidation in Chasmagnathus brain, is induced in the crab's brain by air exposure. Moreover, nuclear brain NF-kappaB is activated by ANGII, and this effect is reversed by saralasin. Our results constitute the first demonstration in an invertebrate that cognitive functions are modulated by an environmental stimulus through a neuropeptide and give evolutionary support to the role of angiotensins in memory processes. Moreover, these results suggest that angiotensinergic system is preserved across evolution not only in its structure and molecular mechanisms, but also in its capability of coordinating specific adaptative responses.

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.

Intraoperative electrostimulation objectifies the assessment of functional nerve preservation after mesorectal excision.

PubMed

Kneist, W; Junginger, T

2007-06-01

To improve nerve-sparing surgery, intraoperative electrical stimulation of pelvic autonomic nerves (INS) has been proposed in urology, gynecology, and visceral surgery. The aim of this study was to assess the impact of INS while monitoring intravesical pressure on the accurate evaluation of pelvic autonomic nerve preservation (PANP) after mesorectal excision. It was sought to determine whether this confirmation is useful in the prediction of postoperative urinary function. Sixty-two patients with mesorectal exzision for rectal cancer were examined prospectively. PANP was assessed visually by the surgeon and with INS. Bladder function was evaluated by post voiding residual volume measurement, rate of recatheterization, rate of long-term urinary catheterisation, and the international prostatic symptom score with quality of life index. INS confirmed bilateral preservation of parasympathetic nerves in 46 patients (74%), and in 10 patients (16%) in at least one side. In six patients (10%), INS failed to confirm PANP. Eleven patients (18%) developed urinary symptoms postoperatively. INS results had a higher sensitivity than visual assessment by the surgeon (82 vs 46%). Values for specificity ranged at 90 and 92%, respectively. Accuracy of INS in predicting PANP was higher (88 vs 83%). The correlation between urinary function and the findings on INS was good (kappa-value: 0.65), correlation between urinary function and visual assessment by the surgeon was fair (kappa-value: 0.40). INS, while monitoring intravesical pressure, accurately predicts bladder function after mesorectal excision. It may provide further insight into pelvic autonomic nerve sparing techniques.

A20 Functional Domains Regulate Subcellular Localization and NF-Kappa B Activation

DTIC Science & Technology

2013-08-15

that the first function to be described for A20 was that of an anti -apoptotic protein (55). They based their choice of experiments and preliminary...mediated apoptosis (55). After positive selection of the resulting clones with neomycin and verification of A20 expression, they compared the...Karposi sarcoma herpesvirus (KSHV) mediated cell transformation (72). K13 can directly activate NF-κB by interacting with the IKK complex and is

Three dimensional dust-acoustic solitary waves in an electron depleted dusty plasma with two-superthermal ion-temperature

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

Borhanian, J.; Shahmansouri, M.

2013-01-15

A theoretical investigation is carried out to study the existence and characteristics of propagation of dust-acoustic (DA) waves in an electron-depleted dusty plasma with two-temperature ions, which are modeled by kappa distribution functions. A three-dimensional cylindrical Kadomtsev-Petviashvili equation governing evolution of small but finite amplitude DA waves is derived by means of a reductive perturbation method. The influence of physical parameters on solitary wave structure is examined. Furthermore, the energy integral equation is used to study the existence domains of the localized structures. It is found that the present model can be employed to describe the existence of positive asmore » well as negative polarity DA solitary waves by selecting special values for parameters of the system, e.g., superthermal index of cold and/or hot ions, cold to hot ion density ratio, and hot to cold ion temperature ratio. This model may be useful to understand the excitation of nonlinear DA waves in astrophysical objects.« less

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.

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...

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...

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...

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.

Mapping forested wetlands in the Great Zhan River Basin through integrating optical, radar, and topographical data classification techniques.

PubMed

Na, X D; Zang, S Y; Wu, C S; Li, W L

2015-11-01

Knowledge of the spatial extent of forested wetlands is essential to many studies including wetland functioning assessment, greenhouse gas flux estimation, and wildlife suitable habitat identification. For discriminating forested wetlands from their adjacent land cover types, researchers have resorted to image analysis techniques applied to numerous remotely sensed data. While with some success, there is still no consensus on the optimal approaches for mapping forested wetlands. To address this problem, we examined two machine learning approaches, random forest (RF) and K-nearest neighbor (KNN) algorithms, and applied these two approaches to the framework of pixel-based and object-based classifications. The RF and KNN algorithms were constructed using predictors derived from Landsat 8 imagery, Radarsat-2 advanced synthetic aperture radar (SAR), and topographical indices. The results show that the objected-based classifications performed better than per-pixel classifications using the same algorithm (RF) in terms of overall accuracy and the difference of their kappa coefficients are statistically significant (p<0.01). There were noticeably omissions for forested and herbaceous wetlands based on the per-pixel classifications using the RF algorithm. As for the object-based image analysis, there were also statistically significant differences (p<0.01) of Kappa coefficient between results performed based on RF and KNN algorithms. The object-based classification using RF provided a more visually adequate distribution of interested land cover types, while the object classifications based on the KNN algorithm showed noticeably commissions for forested wetlands and omissions for agriculture land. This research proves that the object-based classification with RF using optical, radar, and topographical data improved the mapping accuracy of land covers and provided a feasible approach to discriminate the forested wetlands from the other land cover types in forestry area.

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.

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 provide evidence that BCL11B associates with intron 2 of the Cot kinase gene to regulate its expression.

Delineation and segmentation of cerebral tumors by mapping blood-brain barrier disruption with dynamic contrast-enhanced CT and tracer kinetics modeling-a feasibility study.

PubMed

Bisdas, S; Yang, X; Lim, C C T; Vogl, T J; Koh, T S

2008-01-01

Dynamic contrast-enhanced (DCE) imaging is a promising approach for in vivo assessment of tissue microcirculation. Twenty patients with clinical and routine computed tomography (CT) evidence of intracerebral neoplasm were examined with DCE-CT imaging. Using a distributed-parameter model for tracer kinetics modeling of DCE-CT data, voxel-level maps of cerebral blood flow (F), intravascular blood volume (vi) and intravascular mean transit time (t1) were generated. Permeability-surface area product (PS), extravascular extracellular blood volume (ve) and extraction ratio (E) maps were also calculated to reveal pathologic locations of tracer extravasation, which are indicative of disruptions in the blood-brain barrier (BBB). All maps were visually assessed for quality of tumor delineation and measurement of tumor extent by two radiologists. Kappa (kappa) coefficients and their 95% confidence intervals (CI) were calculated to determine the interobserver agreement for each DCE-CT map. There was a substantial agreement for the tumor delineation quality in the F, ve and t1 maps. The agreement for the quality of the tumor delineation was excellent for the vi, PS and E maps. Concerning the measurement of tumor extent, excellent and nearly excellent agreement was achieved only for E and PS maps, respectively. According to these results, we performed a segmentation of the cerebral tumors on the base of the E maps. The interobserver agreement for the tumor extent quantification based on manual segmentation of tumor in the E maps vs. the computer-assisted segmentation was excellent (kappa = 0.96, CI: 0.93-0.99). The interobserver agreement for the tumor extent quantification based on computer segmentation in the mean images and the E maps was substantial (kappa = 0.52, CI: 0.42-0.59). This study illustrates the diagnostic usefulness of parametric maps associated with BBB disruption on a physiology-based approach and highlights the feasibility for automatic segmentation of cerebral tumors.

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.

Using Discrete Loss Functions and Weighted Kappa for Classification: An Illustration Based on Bayesian Network Analysis

ERIC Educational Resources Information Center

Zwick, Rebecca; Lenaburg, Lubella

2009-01-01

In certain data analyses (e.g., multiple discriminant analysis and multinomial log-linear modeling), classification decisions are made based on the estimated posterior probabilities that individuals belong to each of several distinct categories. In the Bayesian network literature, this type of classification is often accomplished by assigning…

Gamma-Secretase and Notch Signaling: Novel Therapeutic Targets In Breast Cancer

DTIC Science & Technology

2005-05-01

Giovarelli,M. et al. 2000. Constitutive activation of NF-kappaB and T-cell leukemia/lymphoma in Notch3 transgenic mice. EMBOJ. 19:3337-3348. 16 14...8217-AATTCAACGGCACAGTCAAAG 9. Maekawa, Y. et al. Deltal- Notch3 interactions bias the functional differentiation of o CCGAGAATG-3’, and reverse, 5

Standardized volume-rendering of contrast-enhanced renal magnetic resonance angiography.

PubMed

Smedby, O; Oberg, R; Asberg, B; Stenström, H; Eriksson, P

2005-08-01

To propose a technique for standardizing volume-rendering technique (VRT) protocols and to compare this with maximum intensity projection (MIP) in regard to image quality and diagnostic confidence in stenosis diagnosis with magnetic resonance angiography (MRA). Twenty patients were examined with MRA under suspicion of renal artery stenosis. Using the histogram function in the volume-rendering software, the 95th and 99th percentiles of the 3D data set were identified and used to define the VRT transfer function. Two radiologists assessed the stenosis pathology and image quality from rotational sequences of MIP and VRT images. Good overall agreement (mean kappa=0.72) was found between MIP and VRT diagnoses. The agreement between MIP and VRT was considerably better than that between observers (mean kappa=0.43). One of the observers judged VRT images as having higher image quality than MIP images. Presenting renal MRA images with VRT gave results in good agreement with MIP. With VRT protocols defined from the histogram of the image, the lack of an absolute gray scale in MRI need not be a major problem.

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

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.

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.

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.

[Reliability and validity of a generic job exposure matrix applied on a small-business].

PubMed

Haro-García, Luis; Celis-Quintal, Germán; López-Rojas, Pablo; Sánchez-Román, Francisco Raúl; Juárez-Pérez, Cuauhtémoc Arturo

2007-01-01

to evaluate the reliability and validity of a generic job exposure matrix (JEM) applied in a small business. procedures to evaluate a JEM integrated by six sections: the number of exposed workers per area, frequency of exposure, time of exposure time, level of exposure, safety controls, and proximity to source of exposure, was evaluated. The JEM also obtains information about possible health effects from exposure to occupational/environment agents. Two observers estimated the risk of exposure to epoxy resins on 31 workers of an epoxy resin facility in Mexico City. The rater agreements between the two observers were assessed through percent agreement (PA), weighted kappa (kappa(w)) and the intraclass correlation coefficient (ICC). disagreements were greater for the number of exposed workers (PA = 61.3, kappa(w) = 0.24, ICC = 0.33), level of exposure (PA= 66.7, kappa(w) = 0.25, ICC= 0.56), and safety controls (PA = 54.8, kappa(w) = 0.23, ICC = 0.69) sections. Percent agreement and kappa(w) were 64% and 0.58, respectively. In accordance with Landis and Koch, Altman, Fleiss, and Byrt classifications for the interpretation of kappa value, the weighted kappa (0.58) ranged from moderate to a fair good level. despite the discordance in some sections, the JEM proved to be useful to identify the risk of exposure in this type of small business.

Efficient receiver tuning using differential evolution strategies

NASA Astrophysics Data System (ADS)

Wheeler, Caleb H.; Toland, Trevor G.

2016-08-01

Differential evolution (DE) is a powerful and computationally inexpensive optimization strategy that can be used to search an entire parameter space or to converge quickly on a solution. The Kilopixel Array Pathfinder Project (KAPPa) is a heterodyne receiver system delivering 5 GHz of instantaneous bandwidth in the tuning range of 645-695 GHz. The fully automated KAPPa receiver test system finds optimal receiver tuning using performance feedback and DE. We present an adaptation of DE for use in rapid receiver characterization. The KAPPa DE algorithm is written in Python 2.7 and is fully integrated with the KAPPa instrument control, data processing, and visualization code. KAPPa develops the technologies needed to realize heterodyne focal plane arrays containing 1000 pixels. Finding optimal receiver tuning by investigating large parameter spaces is one of many challenges facing the characterization phase of KAPPa. This is a difficult task via by-hand techniques. Characterizing or tuning in an automated fashion without need for human intervention is desirable for future large scale arrays. While many optimization strategies exist, DE is ideal for time and performance constraints because it can be set to converge to a solution rapidly with minimal computational overhead. We discuss how DE is utilized in the KAPPa system and discuss its performance and look toward the future of 1000 pixel array receivers and consider how the KAPPa DE system might be applied.

Comparison of manual sleep staging with automated neural network-based analysis in clinical practice.

PubMed

Caffarel, Jennifer; Gibson, G John; Harrison, J Phil; Griffiths, Clive J; Drinnan, Michael J

2006-03-01

We have compared sleep staging by an automated neural network (ANN) system, BioSleep (Oxford BioSignals) and a human scorer using the Rechtschaffen and Kales scoring system. Sleep study recordings from 114 patients with suspected obstructed sleep apnoea syndrome (OSA) were analysed by ANN and by a blinded human scorer. We also examined human scorer reliability by calculating the agreement between the index scorer and a second independent blinded scorer for 28 of the 114 studies. For each study, we built contingency tables on an epoch-by-epoch (30 s epochs) comparison basis. From these, we derived kappa (kappa) coefficients for different combinations of sleep stages. The overall agreement of automatic and manual scoring for the 114 studies for the classification {wake / light-sleep / deep-sleep / REM} was poor (median kappa = 0.305) and only a little better (kappa = 0.449) for the crude {wake / sleep} distinction. For the subgroup of 28 randomly selected studies, the overall agreement of automatic and manual scoring was again relatively low (kappa = 0.331 for {wake light-sleep / deep-sleep REM} and kappa = 0.505 for {wake / sleep}), whereas inter-scorer reliability was higher (kappa = -0.641 for {wake / light-sleep / deep-sleep / REM} and kappa = 0.737 for {wake / sleep}). We conclude that such an ANN-based analysis system is not sufficiently accurate for sleep study analyses using the R&K classification system.

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 discussed. PMID:3926938

Activation of peroxisome proliferator-activated receptor beta/delta inhibits lipopolysaccharide-induced cytokine production in adipocytes by lowering nuclear factor-kappaB activity via extracellular signal-related kinase 1/2.

PubMed

Rodríguez-Calvo, Ricardo; Serrano, Lucía; Coll, Teresa; Moullan, Norman; Sánchez, Rosa M; Merlos, Manuel; Palomer, Xavier; Laguna, Juan C; Michalik, Liliane; Wahli, Walter; Vázquez-Carrera, Manuel

2008-08-01

Chronic activation of the nuclear factor-kappaB (NF-kappaB) in white adipose tissue leads to increased production of pro-inflammatory cytokines, which are involved in the development of insulin resistance. It is presently unknown whether peroxisome proliferator-activated receptor (PPAR) beta/delta activation prevents inflammation in adipocytes. First, we examined whether the PPARbeta/delta agonist GW501516 prevents lipopolysaccharide (LPS)-induced cytokine production in differentiated 3T3-L1 adipocytes. Treatment with GW501516 blocked LPS-induced IL-6 expression and secretion by adipocytes and the subsequent activation of the signal transducer and activator of transcription 3 (STAT3)-Suppressor of cytokine signaling 3 (SOCS3) pathway. This effect was associated with the capacity of GW501516 to impede LPS-induced NF-kappaB activation. Second, in in vivo studies, white adipose tissue from Zucker diabetic fatty (ZDF) rats, compared with that of lean rats, showed reduced PPARbeta/delta expression and PPAR DNA-binding activity, which was accompanied by enhanced IL-6 expression and NF-kappaB DNA-binding activity. Furthermore, IL-6 expression and NF-kappaB DNA-binding activity was higher in white adipose tissue from PPARbeta/delta-null mice than in wild-type mice. Because mitogen-activated protein kinase-extracellular signal-related kinase (ERK)1/2 (MEK1/2) is involved in LPS-induced NF-kappaB activation in adipocytes, we explored whether PPARbeta/delta prevented NF-kappaB activation by inhibiting this pathway. Interestingly, GW501516 prevented ERK1/2 phosphorylation by LPS. Furthermore, white adipose tissue from animal showing constitutively increased NF-kappaB activity, such as ZDF rats and PPARbeta/delta-null mice, also showed enhanced phospho-ERK1/2 levels. These findings indicate that activation of PPARbeta/delta inhibits enhanced cytokine production in adipocytes by preventing NF-kappaB activation via ERK1/2, an effect that may help prevent insulin resistance.

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.

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

Development and test-retest reliability of an extended version of the Nordic Musculoskeletal Questionnaire (NMQ-E): a screening instrument for musculoskeletal pain.

PubMed

Dawson, Anna P; Steele, Emily J; Hodges, Paul W; Stewart, Simon

2009-05-01

The Nordic Musculoskeletal Questionnaire (NMQ) quantifies musculoskeletal pain and activity prevention in 9 body regions. The purpose of this study was to develop an extended NMQ (NMQ-E) to collect greater information regarding musculoskeletal pain, examine test-retest reliability and the reproducibility of alternate administration methods. Reliability was examined using observed proportion of agreement for all (P(o)), positive (P(pos)) and negative (P(neg)) responses, kappa (kappa), proportion of maximum kappa achieved (kappa/kappa(max)), intra-class correlation coefficient (ICC) and standard error of measurement (SEM). The NMQ-E was self-administered by 59 Bachelor of Nursing students at a 24-h interval with mean P(o) = 0.88-0.98 and kappa/kappa(max) = 0.71-0.96 for 10 dichotomous questions and mean ICC((2,1)) = 0.97 and SEM = 1.05 years for the age at symptom onset question. The NMQ-E was completed via self and interview administration by 31 student nurses at a 0.97 +/- 1.14 day interval with mean P(o) = 0.92-0.98 and kappa/kappa(max) = 0.76-1.00 for binary questions and mean ICC((2,1)) = 0.90 and SEM = 1.51 years for age at symptom onset data. In both sub-studies, mean P(pos) was lower than mean P(neg) and low prevalence reduced kappa in many instances. The NMQ-E collects reliable information regarding the onset, prevalence, and consequences of musculoskeletal pain and can be administered by self-completion and personal interview. This study presents an NMQ-E that collects reliable information regarding the onset, prevalence, and consequences of musculoskeletal pain in 9 body regions. The NMQ-E can be utilized in descriptive studies or longitudinal studies of disease outcome and can be administered via self-completion and personal interview.

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.

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.

Nutritional status of children and adolescents based on body mass index: agreement between World Health Organization and International Obesity Task Force

PubMed Central

Cavazzotto, Timothy Gustavo; Brasil, Marcos Roberto; Oliveira, Vinicius Machado; da Silva, Schelyne Ribas; Ronque, Enio Ricardo V.; Queiroga, Marcos Roberto; Serassuelo, Helio

2014-01-01

Objective: To investigate the agreement between two international criteria for classification of children and adolescents nutritional status. Methods: The study included 778 girls and 863 boys aged from six to 13 years old. Body mass and height were measured and used to calculate the body mass index. Nutritional status was classified according to the cut-off points defined by the World Health Organization and the International Obesity Task Force. The agreement was evaluated using Kappa statistic and weighted Kappa. Results: In order to classify the nutritional status, the agreement between the criteria was higher for the boys (Kappa 0.77) compared to girls (Kappa 0.61). The weighted Kappa was also higher for boys (0.85) in comparison to girls (0.77). Kappa index varied according to age. When the nutritional status was classified in only two categories - appropriate (thinness + accentuated thinness + eutrophy) and overweight (overweight + obesity + severe obesity) -, the Kappa index presented higher values than those related to the classification in six categories. Conclusions: A substantial agreement was observed between the criteria, being higher in males and varying according to the age. PMID:24676189

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.

On the characteristics of obliquely propagating electrostatic structures in non-Maxwellian plasmas in the presence of ion pressure anisotropy

NASA Astrophysics Data System (ADS)

Adnan, Muhammad; Qamar, Anisa; Mahmood, Shahzad; Kourakis, Ioannis

2017-03-01

The dynamical characteristics of large amplitude ion-acoustic waves are investigated in a magnetized plasma comprising ions presenting space asymmetry in the equation of state and non-Maxwellian electrons. The anisotropic ion pressure is defined using the double adiabatic Chew-Golberger-Low theory. An excess in the superthermal component of the electron population is assumed, in agreement with long-tailed (energetic electron) distribution observations in space plasmas; this is modeled via a kappa-type distribution function. Large electrostatic excitations are assumed to propagate in a direction oblique to the external magnetic field. In the linear (small amplitude) regime, two electrostatic modes are shown to exist. The properties of arbitrary amplitude (nonlinear) obliquely propagating ion-acoustic solitary excitations are thus investigated via a pseudomechanical energy balance analogy, by adopting a Sagdeev potential approach. The combined effect of the ion pressure anisotropy and excess superthermal electrons is shown to alter the parameter region where solitary waves can exist. An excess in the suprathermal particles is thus shown to be associated with solitary waves, which are narrower, faster, and of larger amplitude. Ion pressure anisotropy, on the other hand, affects the amplitude of the solitary waves, which become weaker (in strength), wider (in spatial extension), and thus slower in comparison with the cold ion case.

A Characterization of Student Reflections in an Introductory Pharmacy Practice Experience Discussion Course.

PubMed

Dinkins, Melissa M; Haltom, Wesley R

2018-04-01

Objective. To characterize weekly student reflections in an introductory pharmacy practice experience (IPPE) discussion course meeting concurrently with IPPE rotations in institutional pharmacy. Methods. A qualitative analysis was conducted to identify themes within weekly reflective statements submitted by second year pharmacy students (P2) enrolled in an IPPE rotation and concurrent discussion course. Weekly reflections from the 2015-2016 offering of the course were reviewed by investigators to identify common themes via an iterative process. Subsequently, investigators coded each submission into one of the identified categories. Initial agreement between investigators was assessed using the Cohen kappa coefficient. Discrepancies between coding were resolved through discussion to reach consensus. Results. A total of 402 reflection assignments were reviewed from 85 P2 students enrolled in the IPPE course. Ten themes were identified, with the most common themes being interprofessional teamwork, pharmacist and technician roles and responsibilities, and policies and procedures. Substantial initial agreement between investigators was found, with the most discrepancies arising within the themes of medication distribution and pharmacy administration/organizational structure. Conclusion. Student reflections on IPPEs centered on 10 key topics, primarily related to distributive, legal, and regulatory functions of institutional pharmacy practice. Structuring an IPPE rotation longitudinally in an academic term, with a concurrent discussion course, builds a framework for regular student reflection.

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

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

de Miguel, E.; Rull, L.F.; Gubbins, K.E.

Using molecular-dynamics computer simulation, we study the dynamical behavior of the isotropic and nematic phases of highly anisotropic molecular fluids. The interactions are modeled by means of the Gay-Berne potential with anisotropy parameters {kappa}=3 and {kappa}{prime}=5. The linear-velocity autocorrelation function shows no evidence of a negative region in the isotropic phase, even at the higher densities considered. The self-diffusion coefficient parallel to the molecular axis shows an anomalous increase with density as the system enters the nematic region. This enhancement in parallel diffusion is also observed in the isotropic side of the transition as a precursor effect. The molecular reorientationmore » is discussed in the light of different theoretical models. The Debye diffusion model appears to explain the reorientational mechanism in the nematic phase. None of the models gives a satisfactory account of the reorientation process in the isotropic phase.« less

Mixed Kappa/Mu Opioid Receptor Agonists: The 6β-Naltrexamines

PubMed Central

Cami-Kobeci, Gerta; Neal, Adrian P.; Bradbury, Faye A.; Purington, Lauren C.; Aceto, Mario D.; Harris, Louis S.; Lewis, John W.; Traynor, John R.; Husbands, Stephen M.

2011-01-01

Ligands from the naltrexamine series have consistently demonstrated agonist activity at kappa opioid receptors (KOR), with varying activity at the mu opioid receptor (MOR). Various 6β-cinnamoylamino derivatives were made with the aim of generating ligands with a KOR agonist/MOR partial agonist profile, as ligands with this activity may be of interest as treatment agents for cocaine abuse. The ligands all displayed the desired high affinity, non-selective binding in vitro and in the functional assays were high efficacy KOR agonists with some partial agonist activity at MOR. Two of the new ligands (12a, 12b) have been evaluated in vivo, with 12a acting as a KOR agonist, and therefore somewhat similar to the previously evaluated analogues 3–6, while 12b displayed predominant MOR agonist activity. PMID:19253970

The role of free kappa and lambda light chains in the pathogenesis and treatment of inflammatory diseases.

PubMed

Esparvarinha, Mojgan; Nickho, Hamid; Mohammadi, Hamed; Aghebati-Maleki, Leili; Abdolalizadeh, Jalal; Majidi, Jafar

2017-07-01

Kappa (κ) or lambda (λ) free light chains (FLCs) are produced from B cells during immunoglobulin synthesis. FLCs have been shown to participate in several key processes of immune responses. They are necessary to adjust PMN functions and assist PMN pre-stimulation. Moreover, they cause mast cell degranulation which releases pro-inflammatory mediators and stimulates local inflammatory responses in some conditions such as inflammatory bowel disease (IBD). Having low molecular weights which may straightly be toxic to proximal tubule cells (PTCs), FLCs can also have an important role in renal diseases. In this review we have highlighted the involvement of light chains in the pathogenesis of some inflammatory diseases and discussed their potential to be the targets of therapeutic purposes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Cyclic stretch induces cyclooxygenase-2 gene expression in vascular endothelial cells via activation of nuclear factor kappa-{beta}

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

Zhao, Haige; Hiroi, Toyoko; Hansen, Baranda S.

2009-11-27

Vascular endothelial cells respond to biomechanical forces, such as cyclic stretch and shear stress, by altering gene expression. Since endothelial-derived prostanoids, such as prostacyclin and thromboxane A{sub 2}, are key mediators of endothelial function, we investigated the effects of cyclic stretch on the expression of genes in human umbilical vein endothelial cells controlling prostanoid synthesis: cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), prostacyclin synthase (PGIS) and thromboxane A{sub 2} synthase (TXAS). COX-2 and TXAS mRNAs were upregulated by cyclic stretch for 24 h. In contrast, PGIS mRNA was decreased and stretch had no effect on COX-1 mRNA expression. We further show that stretch-inducedmore » upregulation of COX-2 is mediated by activation of the NF-{kappa}{beta} signaling pathway.« less

Binocular lens tilt and decentration measurements in healthy subjects with phakic eyes.

PubMed

Schaeffel, Frank

2008-05-01

Tilt and decentration of the natural crystalline lens affect optical quality of the foveal image. However, little is known about the distributions of these variables in healthy subjects with phakic eyes and about their correlations in both eyes. A simple, portable, easy-to-use, and partially automated device was developed to study lens tilt and decentration in both eyes of 11 healthy subjects with phakic eyes. The first, third, and fourth Purkinje images (P1, P3, P4) were visualized using a single infrared (IR) light-emitting diode (LED), a planar lens (F = 85 mm; f/number of 1.4), and an infrared sensitive analog video camera. Software was developed to mark pupil edges and positions of P1, P4, and P3 with the cursor of the computer mouse, for three different gaze positions, and an automated regression analysis determined the gaze position that superimposed the third and fourth Purkinje images, the gaze direction for which the lens was oriented perpendicularly to the axis of the IR LED. In this position, lens decentration was determined as the linear distance of the superimposed P3/P4 positions from the pupil center. Contrary to previous approaches, a short initial fixation of a green LED with known angular position calibrated the device as a gaze tracker, and no further positional information was necessary on fixation targets. Horizontal and vertical kappa, horizontal and vertical lens tilt, and vertical lens decentration were highly correlated in both eyes of the subjects, whereas horizontal decentration of the lens was not. There was a large variability of kappa (average horizontal kappa -1.63 degrees +/- 1.77 degrees [left eyes] and +2.07 degrees +/- 2.68 degrees [right eyes]; average vertical kappa +2.52 degrees +/- 1.30 degrees [left eyes] and +2.77 degrees +/- 1.65 degrees [right eyes]). Standard deviation from three repeated measurements ranged from 0.28 degrees to 0.51 degrees for kappa, 0.36 degrees to 0.91 degrees for horizontal lens tilt, and 0.36 degrees to 0.48 degrees for vertical lens tilt. Decentration was measured with standard deviations ranging from 0.02 mm to 0.05 mm. All lenses were found tilted to the temporal side with respect to the fixation axis (on average by 4.6 degrees ). They were also decentered downward with respect to the pupil center by approximately 0.3 mm. Lens tilts and positions could be conveniently measured with the described portable device, a video camera with a large lens. That the lenses were tilted to the temporal side in both eyes, even if corrected for kappa, was unexpected. That they were displaced downward with respect to the pupil center could be related to gravity.

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.

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.

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

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.

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.

Stabilizing IkappaBalpha by "consensus" design.

PubMed

Ferreiro, Diego U; Cervantes, Carla F; Truhlar, Stephanie M E; Cho, Samuel S; Wolynes, Peter G; Komives, Elizabeth A

2007-01-26

IkappaBalpha is the major regulator of transcription factor NF-kappaB function. The ankyrin repeat region of IkappaBalpha mediates specific interactions with NF-kappaB dimers, but ankyrin repeats 1, 5 and 6 display a highly dynamic character when not in complex with NF-kappaB. Using chemical denaturation, we show here that IkappaBalpha displays two folding transitions: a non-cooperative conversion under weak perturbation, and a major cooperative folding phase upon stronger insult. Taking advantage of a native Trp residue in ankyrin repeat (AR) 6 and engineered Trp residues in AR2, AR4 and AR5, we show that the cooperative transition involves AR2 and AR3, while the non-cooperative transition involves AR5 and AR6. The major structural transition can be affected by single amino acid substitutions converging to the "consensus" ankyrin repeat sequence, increasing the native state stability significantly. We further characterized the structural and dynamic properties of the native state ensemble of IkappaBalpha and the stabilized mutants by H/(2)H exchange mass spectrometry and NMR. The solution experiments were complemented with molecular dynamics simulations to elucidate the microscopic origins of the stabilizing effect of the consensus substitutions, which can be traced to the fast conformational dynamics of the folded ensemble.

Berberine suppresses in vitro migration and invasion of human SCC-4 tongue squamous cancer cells through the inhibitions of FAK, IKK, NF-kappaB, u-PA and MMP-2 and -9.

PubMed

Ho, Yung-Tsuan; Yang, Jai-Sing; Li, Tsai-Chung; Lin, Jen-Jyh; Lin, Jaung-Geng; Lai, Kuang-Chi; Ma, Chia-Yu; Wood, W Gibson; Chung, Jing-Gung

2009-07-08

There is increasing evidence that urokinase-type plasminogen activator (u-PA) and matrix metalloproteinases (MMPs) play an important role in cancer metastasis and angiogenesis. Inhibition of u-PA and MMPs could suppress migration and invasion of cancer cells. Berberine, one of the main constituents of the plant Rhizoma coptidis, is a type of isoquinoline alkaloid, reported to have anti-cancer effects in different human cancer cell lines. There is however, no available information on effects of berberine on migration and invasion of human tongue cancer cells. Here, we report that berberine inhibited migration and invasion of human SCC-4 tongue squamous carcinoma cells. This action was mediated by the p-JNK, p-ERK, p-p38, IkappaK and NF-kappaB signaling pathways resulting in inhibition of MMP-2 and -9 in human SCC-4 tongue squamous carcinoma cells. Our Western blowing analysis also showed that berberine inhibited the levels of urokinase-plasminogen activator (u-PA). These results suggest that berberine down-regulates u-PA, MMP-2 and -9 expressions in SCC-4 cells through the FAK, IKK and NF-kappaB mediated pathways and a novel function of berberine is to inhibit the invasive capacity of malignant cells.

NADPH oxidase is not an essential mediator of oxidative stress or liver injury in murine MCD diet-induced steatohepatitis.

PubMed

dela Peña, Aileen; Leclercq, Isabelle A; Williams, Jacqueline; Farrell, Geoffrey C

2007-02-01

Hepatic oxidative stress is a key feature of metabolic forms of steatohepatitis, but the sources of pro-oxidants are unclear. The NADPH oxidase complex is critical for ROS generation in inflammatory cells; loss of any one component (e.g., gp91phox) renders NADPH oxidase inactive. We tested whether activated inflammatory cells contribute to oxidant stress in steatohepatitis. gp91phox-/- and wildtype (wt) mice were fed a methionine and choline-deficient (MCD) diet. Serum ALT, hepatic triglycerides, histopathology, lipid peroxidation, activation of NF-kappaB, expression of NF-kappaB-regulated genes and macrophage chemokines were measured. After 10 days of MCD dietary feeding, gp91phox-/- and wt mice displayed equivalent hepatocellular injury. After 8 weeks, there were fewer activated macrophages in livers of gp91phox-/- mice than controls, despite similar mRNA levels for MCP and MIP chemokines, but fibrosis was similar. NF-kappaB activation and increased expression of ICAM-1, TNF-alpha and COX-2 mRNA were evident in both genotypes, but in gp91phox-/- mice, expression of these genes was confined to hepatocytes. A functional NADPH oxidase complex does not contribute importantly to oxidative stress in this model and therefore is not obligatory for induction or perpetuation of dietary steatohepatitis.

A DFT and semiempirical model-based study of opioid receptor affinity and selectivity in a group of molecules with a morphine structural core.

PubMed

Bruna-Larenas, Tamara; Gómez-Jeria, Juan S

2012-01-01

We report the results of a search for model-based relationships between mu, delta, and kappa opioid receptor binding affinity and molecular structure for a group of molecules having in common a morphine structural core. The wave functions and local reactivity indices were obtained at the ZINDO/1 and B3LYP/6-31G(∗∗) levels of theory for comparison. New developments in the expression for the drug-receptor interaction energy expression allowed several local atomic reactivity indices to be included, such as local electronic chemical potential, local hardness, and local electrophilicity. These indices, together with a new proposal for the ordering of the independent variables, were incorporated in the statistical study. We found and discussed several statistically significant relationships for mu, delta, and kappa opioid receptor binding affinity at both levels of theory. Some of the new local reactivity indices incorporated in the theory appear in several equations for the first time in the history of model-based equations. Interaction pharmacophores were generated for mu, delta, and kappa receptors. We discuss possible differences regulating binding and selectivity in opioid receptor subtypes. This study, contrarily to the statistically backed ones, is able to provide a microscopic insight of the mechanisms involved in the binding process.

Apparent Transition Behavior of Widely-Used Turbulence Models

NASA Technical Reports Server (NTRS)

Rumsey, Christopher L.

2006-01-01

The Spalart-Allmaras and the Menter SST kappa-omega turbulence models are shown to have the undesirable characteristic that, for fully turbulent computations, a transition region can occur whose extent varies with grid density. Extremely fine two-dimensional grids over the front portion of an airfoil are used to demonstrate the effect. As the grid density is increased, the laminar region near the nose becomes larger. In the Spalart-Allmaras model this behavior is due to convergence to a laminar-behavior fixed point that occurs in practice when freestream turbulence is below some threshold. It is the result of a feature purposefully added to the original model in conjunction with a special trip function. This degenerate fixed point can also cause nonuniqueness regarding where transition initiates on a given grid. Consistent fully turbulent results can easily be achieved by either using a higher freestream turbulence level or by making a simple change to one of the model constants. Two-equation kappa-omega models, including the SST model, exhibit strong sensitivity to numerical resolution near the area where turbulence initiates. Thus, inconsistent apparent transition behavior with grid refinement in this case does not appear to stem from the presence of a degenerate fixed point. Rather, it is a fundamental property of the kappa-omega model itself, and is not easily remedied.

3,4-dichloropropionaniline suppresses normal macrophage function.

PubMed

Ustyugova, Irina V; Frost, Laura L; Van Dyke, Knox; Brundage, Kathleen M; Schafer, Rosana; Barnett, John B

2007-06-01

Macrophages are a critical part of the innate immune response and natural surveillance mechanisms. As such, proper macrophage function is crucial for engulfing bacterial pathogens through phagocytosis and destroying them by generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). The production of a number of cytokines by macrophages, such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6, plays an important role in the initiation of the acquired immune response creating an inflammatory environment favorable for fighting a bacterial infection. 3,4-Dichloropropionaniline (DCPA) suppresses several inflammatory parameters, including TNF-alpha production through a mechanism where nuclear factor-kappaB (NF-kappaB)-DNA binding is inhibited but not entirely abrogated. The goal of the present study was to evaluate the effects of DCPA on the inflammatory mediators of macrophages, including ROS and RNS in both murine peritoneal exudate cells and the human monocytic cell line, THP-1. The ability to perform phagocytosis and directly kill Listeria monocytogenes was also assessed. The results indicate that DCPA decreases the ability of both types of macrophages to phagocytize beads and generate both types of reactive species, which was correlated with a decrement in listericidal activity. These results demonstrate that DCPA has profound effects on macrophage function and provide insight into the potential mechanisms of immunosuppression by DCPA.

Tula and Puumala hantavirus NSs ORFs are functional and the products inhibit activation of the interferon-beta promoter.

PubMed

Jääskeläinen, Kirsi M; Kaukinen, Pasi; Minskaya, Ekaterina S; Plyusnina, Angelina; Vapalahti, Olli; Elliott, Richard M; Weber, Friedemann; Vaheri, Antti; Plyusnin, Alexander

2007-10-01

The S RNA genome segment of hantaviruses carried by Arvicolinae and Sigmodontinae rodents encodes the nucleocapsid (N) protein and has an overlapping (+1) open reading frame (ORF) for a putative nonstructural protein (NSs). The aim of this study was to determine whether the ORF is functional. A protein corresponding to the predicted size of Tula virus (TULV) NSs was detected using coupled in vitro transcription and translation from a cloned S segment cDNA, and a protein corresponding to the predicted size of Puumala virus (PUUV) NSs was detected in infected cells by Western blotting with an anti-peptide serum. The activities of the interferon beta (IFN-beta) promoter, and nuclear factor kappa B (NF-kappaB)- and interferon regulatory factor-3 (IRF-3) responsive promoters, were inhibited in COS-7 cells transiently expressing TULV or PUUV NSs. Also IFN-beta mRNA levels in IFN-competent MRC5 cells either infected with TULV or transiently expressing NSs were decreased. These data demonstrate that Tula and Puumala hantaviruses have a functional NSs ORF. The findings may explain why the NSs ORF has been preserved in the genome of most hantaviruses during their long evolution and why hantavirus-infected cells secrete relatively low levels of IFNs. (c) 2007 Wiley-Liss, Inc.

A medical record review for functional somatic symptoms in children.

PubMed

Rask, Charlotte Ulrikka; Borg, Carsten; Søndergaard, Charlotte; Schulz-Pedersen, Søren; Thomsen, Per Hove; Fink, Per

2010-04-01

The objectives of this study were to develop and test a systematic medical record review for functional somatic symptoms (FSSs) in paediatric patients and to estimate the inter-rater reliability of paediatricians' recognition of FSSs and their associated impairments while using this method. We developed the Medical Record Review for Functional Somatic Symptoms in Children (MRFC) for retrospective medical record review. Described symptoms were categorised as probably, definitely, or not FSSs. FSS-associated impairment was also determined. Three paediatricians performed the MRFC on the medical records of 54 children with a diagnosed, well-defined physical disease and 59 with 'symptom' diagnoses. The inter-rater reliabilities of the recognition and associated impairment of FSSs were tested on 20 of these records. The MRFC allowed identification of subgroups of children with multisymptomatic FSSs, long-term FSSs, and/or impairing FSSs. The FSS inter-rater reliability was good (combined kappa=0.69) but only fair as far as associated impairment was concerned (combined kappa=0.29). In the hands of skilled paediatricians, the MRFC is a reliable method for identifying paediatric patients with diverse types of FSSs for clinical research. However, additional information is needed for reliable judgement of impairment. The method may also prove useful in clinical practice. Copyright 2010 Elsevier Inc. All rights reserved.

High-Resolution Source Parameter and Site Characteristics Using Near-Field Recordings - Decoding the Trade-off Problems Between Site and Source

NASA Astrophysics Data System (ADS)

Chen, X.; Abercrombie, R. E.; Pennington, C.

2017-12-01

Recorded seismic waveforms include contributions from earthquake source properties and propagation effects, leading to long-standing trade-off problems between site/path effects and source effects. With near-field recordings, the path effect is relatively small, so the trade-off problem can be simplified to between source and site effects (commonly referred as "kappa value"). This problem is especially significant for small earthquakes where the corner frequencies are within similar ranges of kappa values, so direct spectrum fitting often leads to systematic biases due to corner frequency and magnitude. In response to the significantly increased seismicity rate in Oklahoma, several local networks have been deployed following major earthquakes: the Prague, Pawnee and Fairview earthquakes. Each network provides dense observations within 20 km surrounding the fault zone, recording tens of thousands of aftershocks between M1 to M3. Using near-field recordings in the Prague area, we apply a stacking approach to separate path/site and source effects. The resulting source parameters are consistent with parameters derived from ground motion and spectral ratio methods from other studies; they exhibit spatial coherence within the fault zone for different fault patches. We apply these source parameter constraints in an analysis of kappa values for stations within 20 km of the fault zone. The resulting kappa values show significantly reduced variability compared to those from direct spectral fitting without constraints on the source spectrum; they are not biased by earthquake magnitudes. With these improvements, we plan to apply the stacking analysis to other local arrays to analyze source properties and site characteristics. For selected individual earthquakes, we will also use individual-pair empirical Green's function (EGF) analysis to validate the source parameter estimations.

Increased presynaptic regulation of dopamine neurotransmission in the nucleus accumbens core following chronic ethanol self-administration in female macaques

PubMed Central

Siciliano, Cody A.; Calipari, Erin S.; Yorgason, Jordan T.; Lovinger, David M.; Mateo, Yolanda; Jimenez, Vanessa A.; Helms, Christa M.; Grant, Kathleen A.; Jones, Sara R.

2016-01-01

Rationale Hypofunction of striatal dopamine neurotransmission, or hypodopaminergia, is a consequence of excessive ethanol use, and is hypothesized to be a critical component of alcoholism, driving alcohol intake in an attempt to restore dopamine levels; however, the neurochemical mechanisms involved in these dopaminergic deficiencies are unknown. Objective Here we examined the specific dopaminergic adaptations that produce hypodopaminergia and contribute to alcohol use disorders using direct, sub-second measurements of dopamine signaling in nonhuman primates following chronic ethanol self-administration. Methods Female rhesus macaques completed one year of daily (22 hr/day) ethanol self-administration. Subsequently, fast-scan cyclic voltammetry was used in nucleus accumbens core brain slices to determine alterations in dopamine terminal function, including release and uptake kinetics, and sensitivity to quinpirole (D2/D3 dopamine receptor agonist) and U50,488 (kappa-opioid receptor agonist) induced inhibition of dopamine release. Results Ethanol drinking greatly increased uptake rates, which were positively correlated with lifetime ethanol intake. Furthermore, the sensitivity of dopamine D2/D3 autoreceptors and kappa-opioid receptors, which both act as negative regulators of presynaptic dopamine release, were moderately and robustly enhanced in ethanol drinkers. Conclusions Greater uptake rates and sensitivity to D2-type autoreceptor and kappa-opioid receptor agonists could converge to drive a hypodopaminergic state, characterized by reduced basal dopamine and an inability to mount appropriate dopaminergic responses to salient stimuli. Together, we outline the specific alterations to dopamine signaling that may drive ethanol-induced hypofunction of the dopamine system, and suggest that the dopamine and dynorphin/kappa-opioid receptor systems may be efficacious pharmcotherapeutic targets in the treatment of alcohol use disorders. PMID:26892380

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.

Evaluation of the properties and reliability of a clinical severity scale for acute asthma in children.

PubMed

Bishop, J; Carlin, J; Nolan, T

1992-01-01

The inter-observer agreement (reliability) and validity of a clinical asthma severity scale (ASS) derived from separate scores of wheeze, heart rate and accessory muscle use (each on a 4-point scale) were studied in 60 children aged between 6 months and 17 years (mean 5.4 years). Independent assessments of these clinical parameters were made by two paediatricians, and they also rated patients as having a mild, moderate, severe or very severe acute episode (clinical judgement rating, CJR). Oxygen saturation (SaO2) was measured concurrently by a Biox 3700 pulse oximeter and readings were categorized as mild (SaO2 greater than or equal to 94%), moderate (91-93%) and severe (less than 91%). Agreement between clinicians was assessed by the weighted kappa statistic (kappa W). Agreement for the ASS score compared to the severity grade obtained from SaO2 was slight (kappa W = 0.34) and compared to CJR the kappa W was 0.55. An ASS score of moderate or worse (greater than 3) had sensitivity of 97% and specificity of 50% for prediction of admission. The maximum frequency and duration of nebulizer therapy following admission were significantly greater for severe patients than for moderate patients. Length of hospital stay did not reflect the ASS score in the emergency department but total duration of functional disability increased with ASS score. The substitution of an adjusted heart rate score for the raw heart rate score used in ASS detracted from scale performance. The ASS is an imprecise but reasonable quantitative measure of the severity of an acute episode of asthma.(ABSTRACT TRUNCATED AT 250 WORDS)

The viral protein A238L inhibits TNF-alpha expression through a CBP/p300 transcriptional coactivators pathway.

PubMed

Granja, Aitor G; Nogal, Maria L; Hurtado, Carolina; Del Aguila, Carmen; Carrascosa, Angel L; Salas, María L; Fresno, Manuel; Revilla, Yolanda

2006-01-01

African swine fever virus (ASFV) is able to inhibit TNF-alpha-induced gene expression through the synthesis of A238L protein. This was shown by the use of deletion mutants lacking the A238L gene from the Vero cell-adapted Ba71V ASFV strain and from the virulent isolate E70. To further analyze the molecular mechanism by which the viral gene controls TNF-alpha, we have used Jurkat cells stably transfected with the viral gene to identify the TNF-alpha regulatory elements involved in the induction of the gene after stimulation with PMA and calcium ionophore. We have thus identified the cAMP-responsive element and kappa3 sites on the TNF-alpha promoter as the responsible of the gene activation, and demonstrate that A238L inhibits TNF-alpha expression through these DNA binding sites. This inhibition was partially reverted by overexpression of the transcriptional factors NF-AT, NF-kappaB, and c-Jun. Furthermore, we present evidence that A238L inhibits the activation of TNF-alpha by modulating NF-kappaB, NF-AT, and c-Jun trans activation through a mechanism that involves CREB binding protein/p300 function, because overexpression of these transcriptional coactivators recovers TNF-alpha promoter activity. In addition, we show that A238L is a nuclear protein that binds to the cyclic AMP-responsive element/kappa3 complex, thus displacing the CREB binding protein/p300 coactivators. Taken together, these results establish a novel mechanism in the control of TNF-alpha gene expression by a viral protein that could represent an efficient strategy used by ASFV to evade the innate immune response.

The role of annexin A1 in expression of matrix metalloproteinase-9 and invasion of breast cancer cells

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

Kang, Hyereen; Ko, Jesang; Jang, Sung-Wuk, E-mail: swjang@amc.seoul.kr

2012-06-22

Highlights: Black-Right-Pointing-Pointer We evaluated the effect of ANXA1 on promoting migration and invasion in MDA-MB-231 cells. Black-Right-Pointing-Pointer ANXA1 siRNA inhibits invasion and migration. Black-Right-Pointing-Pointer ANXA1 regulates MMP-9 expression and activity. Black-Right-Pointing-Pointer ANX-1 siRNA inhibits the activation of NF-{kappa}B in MDA-MB-231 cells. -- Abstract: Matrix metalloproteinase-9 (MMP-9) plays an important role in the invasion and metastasis of cancer cells. However, the regulatory mechanism of MMP-9 expression and its biological effects on breast cancer development remain obscure. In the current study, we examined the potential role of annexin A1 (ANXA1) in regulating migration and invasion in breast cancer cell lines. Both ANXA1more » mRNA and protein are expressed in the highly invasive, hormone-insensitive human breast cancer cell lines MDA-MB-231 and SKBr3, but not in the hormone-responsive cell lines MCF-7 and T47D. Downregulation of ANXA1 expression with specific small interfering RNAs (ANXA1 siRNA) in MDA-MB-231 cells resulted in decreased cancer cell migration and invasion. Ablation of ANXA1 expression decreases the expression of MMP-9 at both the mRNA and protein levels and also reduces the proteolytic activity of MMP-9 in MDA-MB-231 cells. Moreover, silencing ANXA1 also decreases the transcriptional activity of MMP-9 by the suppression of nuclear factor kappa-B (NF-{kappa}B) activity. Collectively, these results indicate that ANXA1 functions as a positive regulator of MMP-9 expression and invasion of breast cancer cells through specific activation of the NF-{kappa}B signaling pathway.« less

Increased presynaptic regulation of dopamine neurotransmission in the nucleus accumbens core following chronic ethanol self-administration in female macaques.

PubMed

Siciliano, Cody A; Calipari, Erin S; Yorgason, Jordan T; Lovinger, David M; Mateo, Yolanda; Jimenez, Vanessa A; Helms, Christa M; Grant, Kathleen A; Jones, Sara R

2016-04-01

Hypofunction of striatal dopamine neurotransmission, or hypodopaminergia, is a consequence of excessive ethanol use and is hypothesized to be a critical component of alcoholism, driving alcohol intake in an attempt to restore dopamine levels; however, the neurochemical mechanisms involved in these dopaminergic deficiencies are not fully understood. Here we examined the specific dopaminergic adaptations that produce hypodopaminergia and contribute to alcohol use disorders using direct, sub-second measurements of dopamine signaling in nonhuman primates following chronic ethanol self-administration. Female rhesus macaques completed 1 year of daily (22 h/day) ethanol self-administration. Subsequently, fast-scan cyclic voltammetry was used in nucleus accumbens core brain slices to determine alterations in dopamine terminal function, including release and uptake kinetics, and sensitivity to quinpirole (D2/D3 dopamine receptor agonist) and U50,488 (kappa opioid receptor agonist) induced inhibition of dopamine release. Ethanol drinking greatly increased uptake rates, which were positively correlated with lifetime ethanol intake. Furthermore, the sensitivity of dopamine D2/D3 autoreceptors and kappa opioid receptors, which both act as negative regulators of presynaptic dopamine release, was moderately and robustly enhanced in ethanol drinkers. Greater uptake rates and sensitivity to D2-type autoreceptor and kappa opioid receptor agonists could converge to drive a hypodopaminergic state, characterized by reduced basal dopamine and an inability to mount appropriate dopaminergic responses to salient stimuli. Together, we outline the specific alterations to dopamine signaling that may drive ethanol-induced hypofunction of the dopamine system and suggest that the dopamine and dynorphin/kappa opioid receptor systems may be efficacious pharmacotherapeutic targets in the treatment of alcohol use disorders.

A preferential p110alpha/gamma PI3K inhibitor attenuates experimental inflammation by suppressing the production of proinflammatory mediators in a NF-kappaB-dependent manner.

PubMed

Dagia, Nilesh M; Agarwal, Gautam; Kamath, Divya V; Chetrapal-Kunwar, Anshu; Gupte, Ravindra D; Jadhav, Mahesh G; Dadarkar, Shruta S; Trivedi, Jacqueline; Kulkarni-Almeida, Asha A; Kharas, Firuza; Fonseca, Lyle C; Kumar, Sanjay; Bhonde, Mandar R

2010-04-01

A promising therapeutic approach to diminish pathological inflammation is to inhibit the increased production and/or biological activity of proinflammatory cytokines (e.g., TNF-alpha, IL-6). The production of proinflammatory cytokines is controlled at the gene level by the activity of transcription factors, such as NF-kappaB. Phosphatidylinositol 3-kinase (PI3K), a lipid kinase, is known to induce the activation of NF-kappaB. Given this, we hypothesized that inhibitors of PI3K activation would demonstrate anti-inflammatory potential. Accordingly, we studied the effects of a preferential p110alpha/gamma PI3K inhibitor (compound 8C; PIK-75) in inflammation-based assays. Mechanism-based assays utilizing human cells revealed that PIK-75-mediated inhibition of PI3K activation is associated with dramatic suppression of downstream signaling events, including AKT phosphorylation, IKK activation, and NF-kappaB transcription. Cell-based assays revealed that PIK-75 potently and dose dependently inhibits in vitro and in vivo production of TNF-alpha and IL-6, diminishes the induced expression of human endothelial cell adhesion molecules (E-selectin, ICAM-1, and VCAM-1), and blocks human monocyte-endothelial cell adhesion. Most importantly, PIK-75, when administered orally in a therapeutic regimen, significantly suppresses the macroscopic and histological abnormalities associated with dextran sulfate sodium-induced murine colitis. The efficacy of PIK-75 in attenuating experimental inflammation is mediated, at least in part, due to the downregulation of pertinent inflammatory mediators in the colon. Collectively, these results provide first evidence that PIK-75 possesses anti-inflammatory potential. Given that PIK-75 is known to exhibit anti-cancer activity, the findings from this study thus reinforce the cross-therapeutic functionality of potential drugs.

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.

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.

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.

Comparison of clinician-predicted to measured low vision outcomes.

PubMed

Chan, Tiffany L; Goldstein, Judith E; Massof, Robert W

2013-08-01

To compare low-vision rehabilitation (LVR) clinicians' predictions of the probability of success of LVR with patients' self-reported outcomes after provision of usual outpatient LVR services and to determine if patients' traits influence clinician ratings. The Activity Inventory (AI), a self-report visual function questionnaire, was administered pre-and post-LVR to 316 low-vision patients served by 28 LVR centers that participated in a collaborative observational study. The physical component of the Short Form-36, Geriatric Depression Scale, and Telephone Interview for Cognitive Status were also administered pre-LVR to measure physical capability, depression, and cognitive status. After patient evaluation, 38 LVR clinicians estimated the probability of outcome success (POS) using their own criteria. The POS ratings and change in functional ability were used to assess the effects of patients' baseline traits on predicted outcomes. A regression analysis with a hierarchical random-effects model showed no relationship between LVR physician POS estimates and AI-based outcomes. In another analysis, kappa statistics were calculated to determine the probability of agreement between POS and AI-based outcomes for different outcome criteria. Across all comparisons, none of the kappa values were significantly different from 0, which indicates that the rate of agreement is equivalent to chance. In an exploratory analysis, hierarchical mixed-effects regression models show that POS ratings are associated with information about the patient's cognitive functioning and the combination of visual acuity and functional ability, as opposed to visual acuity or functional ability alone. Clinicians' predictions of LVR outcomes seem to be influenced by knowledge of patients' cognitive functioning and the combination of visual acuity and functional ability-information clinicians acquire from the patient's history and examination. However, clinicians' predictions do not agree with observed changes in functional ability from the patient's perspective; they are no better than chance.

ICAM-1 and AMPK regulate cell detachment and apoptosis by N-methyl-N Prime -nitro-N-nitrosoguanidine, a widely spread environmental chemical, in human hormone-refractory prostate cancers

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

Chen, Yi-Cheng; Lu, Pin-Hsuan; Hsu, Jui-Ling

2011-12-15

Poly(ADP-ribose) polymerase-1 (PARP-1), a sensor of DNA damage, plays a crucial role in the regulation of DNA repair. PARP-1 hyperactivation causes DNA damage and cell death. The underlying mechanism is complicated and is through diverse pathways. The understanding of responsible signaling pathways may offer implications for effective therapies. After concentration-response determination of N-Methyl-N Prime -Nitro-N-Nitrosoguanidine (MNNG, a PARP-1 activating agent and an environmental mutagen) in human hormone-refractory prostate cancers, the data showed that concentrations below 5 {mu}M did not change cell survival but cause a time-dependent up-regulation of intracellular adhesion molecule-1 (ICAM-1) in mRNA, total protein and cell surface levels.more » Detection of phosphorylation and degradation of I{kappa}B-{alpha} and nuclear translocation of NF-{kappa}B showed that MNNG induced the activation of NF-{kappa}B that was responsible for the ICAM-1 up-regulation since PDTC (a NF-{kappa}B inhibitor) significantly abolished this effect. However, higher concentrations (e.g., 10 {mu}M) of MNNG induced a 61% detachment of the cells which were apoptosis associated with the activation of AMP-activated protein kinase (AMPK), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK). Further identification showed that both AMPK and JNK other than p38 MAPK functionally contributed to cell death. The remaining 39% attached cells were survival associated with high ICAM-1 expression. In conclusion, the data suggest that NF-{kappa}B-dependent up-regulation of ICAM-1 plays a key role on cell attachment and survival; whereas, activation of AMPK and JNK participates in cytotoxic signaling pathways in detached cells caused by PARP-1 activation. Highlights: Black-Right-Pointing-Pointer Low level of DNA damage helps cell attachment and survival via ICAM-1 upregulation. Black-Right-Pointing-Pointer High level of DNA damage causes AMPK- and JNK-involved cell detachment and death. Black-Right-Pointing-Pointer The study provides an anticancer approach targeting PARP-1 and DNA damage response.« less

The bile acid deoxycholic acid has a non-linear dose response for DNA damage and possibly NF-kappaB activation in oesophageal cells, with a mechanism of action involving ROS.

PubMed

Jenkins, G J S; Cronin, J; Alhamdani, A; Rawat, N; D'Souza, F; Thomas, T; Eltahir, Z; Griffiths, A P; Baxter, J N

2008-09-01

Deoxycholic acid (DCA) is a secondary bile acid implicated in various cancers of the gastrointestinal (GI) tract. In oesophageal adenocarcinoma, DCA is believed to contribute to carcinogenesis during reflux where stomach contents enter the lower oesophagus. It is imperative that we understand the mechanisms whereby oesophageal carcinogens function in order that therapeutic options may be developed. We have previously shown that DCA can damage chromosomes and does so through its generation of reactive oxygen species (ROS). We show here, after detailed experiments, that DCA appears to have a non-linear dose response for DNA damage. DCA induces DNA damage (as measured by the micronucleus assay) at doses of 100 microM and higher in oesophageal OE33 cells, but fails to induce such DNA damage below this cut-off dose. We also show that in terms of NF-kappaB activation (as measured by up-regulation of two NF-kappaB target genes) by DCA, a similar dose response is observed. This dose-response data may be important clinically as DCA exposure to the oesophagus may be used as a way to identify the 10% of Barrett's oesophagus patients currently progressing to cancer from the 90% of patients who do not progress. Only quantitative studies measuring DCA concentrations in refluxates correlated with histological progression will answer this question. We further show here that ROS are behind DCAs ability to activate NF-kappaB as antioxidants (epigallocatechin gallate, resveratrol and vitamin C) abrogate DCAs ability to up-regulate NF-kappaB-controlled genes. In conclusion, low doses of DCA appear to be less biologically significant in vitro. If this were to be confirmed in vivo, it might suggest that reflux patients with low DCA concentrations may be at a lower risk of cancer progression compared to patients with high levels of DCA in their refluxate. Either way, antioxidant supplementation may possibly help prevent the deleterious effects of DCA in the whole GI tract.

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.

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.

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

Inter- and intraobserver agreement in 24-hour combined multiple intraluminal impedance and pH measurement in children.

PubMed

Pilic, Denisa; Höfs, Carolin; Weitmann, Sandra; Nöh, Frank; Fröhlich, Thorsten; Skopnik, Heino; Köhler, Henrik; Wenzl, Tobias G; Schmidt-Choudhury, Anjona

2011-09-01

Assessment of intra- and interobserver agreement in multiple intraluminal impedance (MII) measurement between investigators from different institutions. Twenty-four 18- to 24-hour MII tracings were randomly chosen from 4 different institutions (6 per center). Software-aided automatic analysis was performed. Each result was validated by 2 independent investigators from the 4 different centers (4 investigator combinations). For intraobserver agreement, 6 measurements were analyzed twice by the same investigator. Agreement between investigators was calculated using the Cohen kappa coefficient. Interobserver agreement: 13 measurements showed a perfect agreement (kappa > 0.8); 9 had a substantial (kappa 0.61-0.8), 1 a moderate (kappa coefficient 0.41 to 0.6), and 1 a fair agreement (kappa coefficient 0.11-0.4). Median kappa value was 0.83. Intraobserver agreement: 5 tracings showed perfect and 1 showed a substantial agreement. The median kappa value was 0.88. Most measurements showed substantial to perfect intra- and interobserver agreement. Still, we found a few outliers presumably caused by poorer signal quality in some tracings rather than being observer dependent. An improvement of analysis results may be achieved by using a standard analysis protocol, a standardized method for judging tracing quality, better training options for method users, and more interaction between investigators from different institutions.

Distinct mechanisms for N-acetylcysteine inhibition of cytokine-induced E-selectin and VCAM-1 expression.

PubMed

Faruqi, R M; Poptic, E J; Faruqi, T R; De La Motte, C; DiCorleto, P E

1997-08-01

We have examined the effects of N-acetyl-L-cysteine (NAC), a well-characterized, thiol-containing antioxidant, on agonist-induced monocytic cell adhesion to endothelial cells (EC). NAC inhibited interleukin-1 (IL-1 beta)-induced, but not basal, adhesion with 50% inhibition at approximately 20 mM. Monocytic cell adhesion to EC in response to tumor necrosis factor-alpha (TNF-alpha), lipopolysaccharide (LPS), alpha-thrombin, or phorbol 12-myristate 13-acetate (PMA) was similarly inhibited by NAC. Unlike published studies with pyrrolidinedithiocarbamate, which specifically inhibited vascular cell adhesion molecule 1 (VCAM-1), NAC inhibited IL-1 beta-induced mRNA and cell surface expression of both E-selectin and VCAM-1. NAC had no effect on the half-life of E-selectin or VCAM-1 mRNA. Although NAC reduced nuclear factor-kappa B (NF-kappa B) activation in EC as measured by gel-shift assays using an oligonucleotide probe corresponding to the consensus NF-kappa B binding sites of the VCAM-1 gene (VCAM-NF-kappa B), the antioxidant had no appreciable effect when an oligomer corresponding to the consensus NF-kappa B binding site of the E-selectin gene (E-selectin-NF-kappa B) was used. Because NF-kappa B has been reported to be redox sensitive, we studied the effects of NAC on the EC redox environment. NAC caused an expected dramatic increase in the reduced glutathione (GSH) levels in EC. In vitro studies demonstrated that whereas the binding affinity of NF-kappa B to the VCAM-NF-kappa B oligomer peaked at a GSH-to-oxidized glutathione (GSSG) ratio of approximately 200 and decreased at higher ratios, the binding to the E-selectin-NF-kappa B oligomer appeared relatively unaffected even at ratios > 400, i.e., those achieved in EC treated with 40 mM NAC. These results suggest that NF-kappa B binding to its consensus sequences in the VCAM-1 and E-selectin gene exhibits marked differences in redox sensitivity, allowing for differential gene expression regulated by the same transcription factor. Our data also demonstrate that NAC increases the GSH-to-GSSG ratio within the EC suggesting one possible mechanism through which this antioxidant inhibits agonist-induced monocyte adhesion to EC.

kappa-Version of Finite Element Method: A New Mathematical and Computational Framework for BVP and IVP

DTIC Science & Technology

2007-01-01

differentiability, fluid-solid interaction, error estimation, re-discretization, moving meshes 16. SECURITY CLASSIFICATION OF: 17 . LIMITATION OF 18. NUMBER...method the weight function is an indepen- dent function v = 0 6 4Ph , with v = 0 on F, if W = W0 on F1. 2. Galerkin method (GM): If Wh is an approximation...This can be demonstrated by considering a simple I-D case (like described above) in which the discretization 17 is uniform with characteristic length

Detecting understory plant invasion in urban forests using LiDAR

NASA Astrophysics Data System (ADS)

Singh, Kunwar K.; Davis, Amy J.; Meentemeyer, Ross K.

2015-06-01

Light detection and ranging (LiDAR) data are increasingly used to measure structural characteristics of urban forests but are rarely used to detect the growing problem of exotic understory plant invaders. We explored the merits of using LiDAR-derived metrics alone and through integration with spectral data to detect the spatial distribution of the exotic understory plant Ligustrum sinense, a rapidly spreading invader in the urbanizing region of Charlotte, North Carolina, USA. We analyzed regional-scale L. sinense occurrence data collected over the course of three years with LiDAR-derived metrics of forest structure that were categorized into the following groups: overstory, understory, topography, and overall vegetation characteristics, and IKONOS spectral features - optical. Using random forest (RF) and logistic regression (LR) classifiers, we assessed the relative contributions of LiDAR and IKONOS derived variables to the detection of L. sinense. We compared the top performing models developed for a smaller, nested experimental extent using RF and LR classifiers, and used the best overall model to produce a predictive map of the spatial distribution of L. sinense across our country-wide study extent. RF classification of LiDAR-derived topography metrics produced the highest mapping accuracy estimates, outperforming IKONOS data by 17.5% and the integration of LiDAR and IKONOS data by 5.3%. The top performing model from the RF classifier produced the highest kappa of 64.8%, improving on the parsimonious LR model kappa by 31.1% with a moderate gain of 6.2% over the county extent model. Our results demonstrate the superiority of LiDAR-derived metrics over spectral data and fusion of LiDAR and spectral data for accurately mapping the spatial distribution of the forest understory invader L. sinense.

Comparing apples and pears: women's perceptions of their body size and shape.

PubMed

Thoma, Marie E; Hediger, Mary L; Sundaram, Rajeshwari; Stanford, Joseph B; Peterson, C Matthew; Croughan, Mary S; Chen, Zhen; Buck Louis, Germaine M

2012-10-01

Obesity is a growing public health problem among reproductive-aged women, with consequences for chronic disease risk and reproductive and obstetric morbidities. Evidence also suggests that body shape (i.e., regional fat distribution) may be independently associated with risk, yet it is not known if women adequately perceive their shape. This study aimed to assess the validity of self-reported body size and shape figure drawings when compared to anthropometric measures among reproductive-aged women. Self-reported body size was ascertained using the Stunkard nine-level figures and self-reported body shape using stylized pear, hourglass, rectangle, and apple figures. Anthropometry was performed by trained researchers. Body size and body mass index (BMI) were compared using Spearman's correlation coefficient. Fat distribution indicators were compared across body shapes for nonobese and obese women using analysis of variance (ANOVA) and Fisher's exact test. Percent agreement and kappa statistics were computed for apple and pear body shapes. The 131 women studied were primarily Caucasian (81%), aged 32 years, with a mean BMI of 27.1 kg/m(2) (range 16.6-52.8 kg/m(2)). The correlation between body size and BMI was 0.85 (p<0.001). Among nonobese women, waist-to-hip ratios (WHR) were 0.75, 0.75, 0.80, and 0.82 for pear, hourglass, rectangle, and apple, respectively (p<0.001). Comparing apples and pears, the percent agreement (kappa) for WHR≥0.80 was 83% (0.55). Self-reported size and shape were consistent with anthropometric measures commonly used to assess obesity and fat distribution, respectively. Self-reported body shape may be a useful proxy measure in addition to body size in large-scale surveys.

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 formation and trp degradation in monocytic THP-1 cells, which is elicited by pro-inflammatory triggers like LPS during innate immune responses.« less

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 study indicate that CREG acts as a novel and potent survival factor in MSCs, and may therefore be a useful therapeutic adjunct for transplanting MSCs into the damaged heart after myocardial infarction.« less

Research diagnostic criteria for temporomandibular disorders (RDC/TMD): development of image analysis criteria and examiner reliability for image analysis.

PubMed

Ahmad, Mansur; Hollender, Lars; Anderson, Quentin; Kartha, Krishnan; Ohrbach, Richard; Truelove, Edmond L; John, Mike T; Schiffman, Eric L

2009-06-01

As part of the Multisite Research Diagnostic Criteria For Temporomandibular Disorders (RDC/TMD) Validation Project, comprehensive temporomandibular joint diagnostic criteria were developed for image analysis using panoramic radiography, magnetic resonance imaging (MRI), and computerized tomography (CT). Interexaminer reliability was estimated using the kappa (kappa) statistic, and agreement between rater pairs was characterized by overall, positive, and negative percent agreement. Computerized tomography was the reference standard for assessing validity of other imaging modalities for detecting osteoarthritis (OA). For the radiologic diagnosis of OA, reliability of the 3 examiners was poor for panoramic radiography (kappa = 0.16), fair for MRI (kappa = 0.46), and close to the threshold for excellent for CT (kappa = 0.71). Using MRI, reliability was excellent for diagnosing disc displacements (DD) with reduction (kappa = 0.78) and for DD without reduction (kappa = 0.94) and good for effusion (kappa = 0.64). Overall percent agreement for pairwise ratings was >or=82% for all conditions. Positive percent agreement for diagnosing OA was 19% for panoramic radiography, 59% for MRI, and 84% for CT. Using MRI, positive percent agreement for diagnoses of any DD was 95% and of effusion was 81%. Negative percent agreement was >or=88% for all conditions. Compared with CT, panoramic radiography and MRI had poor and marginal sensitivity, respectively, but excellent specificity in detecting OA. Comprehensive image analysis criteria for the RDC/TMD Validation Project were developed, which can reliably be used for assessing OA using CT and for disc position and effusion using MRI.

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.

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

Spleen tyrosine kinase mediates high glucose-induced transforming growth factor-{beta}1 up-regulation in proximal tubular epithelial cells

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

Yang, Won Seok; Chang, Jai Won; Han, Nam Jeong

The role of spleen tyrosine kinase (Syk) in high glucose-induced intracellular signal transduction has yet to be elucidated. We investigated whether Syk is implicated in high glucose-induced transforming growth factor-{beta}1 (TGF-{beta}1) up-regulation in cultured human proximal tubular epithelial cells (HK-2 cell). High glucose increased TGF-{beta}1 gene expression through Syk, extracellular signal-regulated kinase (ERK), AP-1 and NF-{kappa}B. High glucose-induced AP-1 DNA binding activity was decreased by Syk inhibitors and U0126 (an ERK inhibitor). Syk inhibitors suppressed high glucose-induced ERK activation, whereas U0126 had no effect on Syk activation. High glucose-induced NF-{kappa}B DNA binding activity was also decreased by Syk inhibitors. Highmore » glucose increased nuclear translocation of p65 without serine phosphorylation of I{kappa}B{alpha} and without degradation of I{kappa}B{alpha}, but with an increase in tyrosine phosphorylation of I{kappa}B{alpha} that may account for the activation of NF-{kappa}B. Both Syk inhibitors and Syk-siRNA attenuated high glucose-induced I{kappa}B{alpha} tyrosine phosphorylation and p65 nuclear translocation. Depletion of p21-activated kinase 2 (Pak2) by transfection of Pak2-siRNA abolished high glucose-induced Syk activation. In summary, high glucose-induced TGF-{beta}1 gene transcription occurred through Pak2, Syk and subsequent ERK/AP-1 and NF-{kappa}B pathways. This suggests that Syk might be implicated in the diabetic kidney disease.« less

Enhanced IL-1{beta}-induced IL-8 production in cystic fibrosis lung epithelial cells is dependent of both mitogen-activated protein kinases and NF-{kappa}B signaling

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

Muselet-Charlier, Celine; Universite Pierre et Marie Curie-Paris 6, Paris, UMR-S719, F-75012; Roque, Telma

2007-06-01

Transcription nuclear factor-{kappa}B (NF-{kappa}B) is hyperactivated in cystic fibrosis (CF) lung epithelial cells, and participates in exaggerated IL-8 production in the CF lung. We recently found that rapid activation of NF-{kappa}B occurred in a CF lung epithelial IB3-1 cell line (CF cells) upon IL-1{beta} stimulation, which was not observed in its CFTR-corrected lung epithelial S9 cell line (corrected cells). To test whether other signaling pathways such as that of mitogen-activated protein kinases (MAPKs) could be involved in IL-1{beta}-induced IL-8 production of CF cells, we investigated ERK1/2, JNK, and p38MAP signaling compared to NF-{kappa}B. Within 30 min, exposure to IL-1{beta} causedmore » high activation of NF-{kappa}B, ERK1/2, p38MAP but not JNK in CF cells compared to corrected cells. Treatment of IL-1{beta}-stimulated CF cells with a series of chemical inhibitors of NF-{kappa}B, ERK1/2, and p38MAP, when used separately, reduced slightly IL-8 production. However, when used together, these inhibitors caused a blockade in IL-1{beta}-induced IL-8 production in CF cells. Understanding of the cross-talk between NF-{kappa}B and MAPKs signaling in CF lung epithelial cells may help in developing new therapeutics to reduce lung inflammation in patients with CF.« less

The Spectral and Statistical Properties of Turbulence Generated by a Vortex/Blade-Tip Interaction

NASA Technical Reports Server (NTRS)

Devenport, William J.; Wittmer, Kenneth S.; Wenger, Christian W.

1997-01-01

The perpendicular interaction of a streamwise vortex with the tip of a lifting blade was studied in incompressible flow to provide information useful to the accurate prediction of helicopter rotor noise and the understanding of vortex dominated turbulent flows. The vortex passed 0.3 chord lengths to the suction side of the blade tip, providing a weak interaction. Single and two-point turbulence measurements were made using sub-miniature four sensor hot-wire probes 15 chord lengths downstream of the blade trailing edge; revealing the mean velocity and Reynolds stress tensor distributions of the turbulence, as well as its spanwise length scales as a function of frequency. The single point measurements show the flow downstream of the blade to be dominated by the interaction of the original tip vortex and the vortex shed by the blade. These vortices rotate about each other under their mutual induction, winding up the turbulent wakes of the blades. This interaction between the vortices appears to be the source of new turbulence in their cores and in the region between them. This turbulence appears to be responsible for some decay in the core of the original vortex, not seen when the blade is removed. The region between the vortices is not only a region of comparatively large stresses, but also one of intense turbulence production. Velocity autospectra measured near its center suggests the presence quasi-periodic large eddies with axes roughly parallel to a line joining the vortex cores. Detailed two-point measurements were made on a series of spanwise cuts through the flow so as to reveal the turbulence scales as they would be seen along the span of an intersecting airfoil. The measurements were made over a range of probe separations that enabled them to be analyzed not only in terms of coherence and phase spectra but also in terms of wave-number frequency (kappa-omega) spectra, computed by transforming the measured cross-spectra with respect to the spanwise separation of the probes. These data clearly show the influence of the coherent eddies in the spiral wake and the turbulent region between the cores. These eddies produce distinct peaks in the upwash velocity kappa-omega spectra, and strong anisotropy manifested both in the decay of the kappa-omega spectrum at larger wave-numbers and in differences between the kappa-omega spectra of different components. None of these features are represented in the von Karman spectrum for isotropic turbulence that is often used in broadband noise computations. Wave-number frequency spectra measured in the cores appear to show some evidence that the turbulence outside sets tip core waves, as has previously been hypothesized. These spectra also provide for the first time a truly objective method for distinguishing velocity fluctuations produced by core wandering from other motions.

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".

Effective Torsion and Spring Constants in a Hybrid Translational-Rotational Oscillator

ERIC Educational Resources Information Center

Nakhoda, Zein; Taylor, Ken

2011-01-01

A torsion oscillator is a vibrating system that experiences a restoring torque given by [tau] = -[kappa][theta] when it experiences a rotational displacement [theta] from its equilibrium position. The torsion constant [kappa] (kappa) is analogous to the spring constant "k" for the traditional translational oscillator (for which the restoring force…

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

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

(/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

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

Source localization of rhythmic ictal EEG activity: a study of diagnostic accuracy following STARD criteria.

PubMed

Beniczky, Sándor; Lantz, Göran; Rosenzweig, Ivana; Åkeson, Per; Pedersen, Birthe; Pinborg, Lars H; Ziebell, Morten; Jespersen, Bo; Fuglsang-Frederiksen, Anders

2013-10-01

Although precise identification of the seizure-onset zone is an essential element of presurgical evaluation, source localization of ictal electroencephalography (EEG) signals has received little attention. The aim of our study was to estimate the accuracy of source localization of rhythmic ictal EEG activity using a distributed source model. Source localization of rhythmic ictal scalp EEG activity was performed in 42 consecutive cases fulfilling inclusion criteria. The study was designed according to recommendations for studies on diagnostic accuracy (STARD). The initial ictal EEG signals were selected using a standardized method, based on frequency analysis and voltage distribution of the ictal activity. A distributed source model-local autoregressive average (LAURA)-was used for the source localization. Sensitivity, specificity, and measurement of agreement (kappa) were determined based on the reference standard-the consensus conclusion of the multidisciplinary epilepsy surgery team. Predictive values were calculated from the surgical outcome of the operated patients. To estimate the clinical value of the ictal source analysis, we compared the likelihood ratios of concordant and discordant results. Source localization was performed blinded to the clinical data, and before the surgical decision. Reference standard was available for 33 patients. The ictal source localization had a sensitivity of 70% and a specificity of 76%. The mean measurement of agreement (kappa) was 0.61, corresponding to substantial agreement (95% confidence interval (CI) 0.38-0.84). Twenty patients underwent resective surgery. The positive predictive value (PPV) for seizure freedom was 92% and the negative predictive value (NPV) was 43%. The likelihood ratio was nine times higher for the concordant results, as compared with the discordant ones. Source localization of rhythmic ictal activity using a distributed source model (LAURA) for the ictal EEG signals selected with a standardized method is feasible in clinical practice and has a good diagnostic accuracy. Our findings encourage clinical neurophysiologists assessing ictal EEGs to include this method in their armamentarium. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

How To Prepare Materials With a Desired Refraction Coefficient?

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

Ramm, A. G.

2010-05-21

In this talk a method is described for preparing materials with a desired refraction coefficient. The method consists of embedding into a material with known refraction coefficient many small particles of size a. The number of particles per unit volume around any point is prescribed, the distance between neighboring particles is O(a{sup (2-kappa/3)}) as a->0, 00. The refraction coefficient is themore » coefficient n{sup 2}(x) in the wave equation [nabla{sup 2}+kappa{sup 2}n{sup 2}(x)]u = 0.« less

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.

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.

Rosiglitazone attenuates NF-{kappa}B-dependent ICAM-1 and TNF-{alpha} production caused by homocysteine via inhibiting ERK{sub 1/2}/p38MAPK activation

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

Bai, Yong-Ping; Liu, Yu-Hui; Chen, Jia

2007-08-17

Previous studies demonstrated an important interaction between nuclear factor-kappaB (NF-{kappa}B) activation and homocysteine (Hcy)-induced cytokines expression in endothelial cells and vascular smooth muscle cells. However, the underlying mechanism remains illusive. In this study, we investigated the effects of Hcy on NF-{kappa}B-mediated sICAM-1, TNF-{alpha} production and the possible involvement of ERK{sub 1/2}/p38MAPK pathway. The effects of rosiglitazone intervention were also examined. Our results show that Hcy increased the levels of sICAM-1 and TNF-{alpha} in cultured human umbilical vein endothelial cells (HUVECs) in a time- and concentration-dependent manner. This effect was significantly depressed by rosiglitazone and different inhibitors (PDTC, NF-{kappa}B inhibitor; PD98059,more » MEK inhibitor; SB203580, p38MAPK specific inhibitor; and staurosporine, PKC inhibitor). Next, we investigated the effect of Hcy on ERK{sub 1/2}/p38MAPK pathway and NF-{kappa}B activity in HUVECs. The results show that Hcy activated both ERK{sub 1/2}/p38MAPK pathway and NF-{kappa}B-DNA-binding activity. These effects were markedly inhibited by rosiglitazone as well as other inhibitors (SB203580, PD98059, and PDTC). Further, the pretreatment of staurosporine abrogated ERK{sub 1/2}/p38MAPK phosphorylation, suggesting that Hcy-induced ERK{sub 1/2}/p38MAPK activation is associated with PKC activity. Our results provide evidence that Hcy-induced NF-{kappa}B activation was mediated by activation of ERK{sub 1/2}/p38MAPK pathway involving PKC activity. Rosiglitazone reduces the NF-{kappa}B-mediated sICAM-1 and TNF-{alpha} production induced by Hcy via inhibition of ERK{sub 1/2}/p38MAPK pa0011thw.« less

TNF{alpha} and IL-1{beta} are mediated by both TLR4 and Nod1 pathways in the cultured HAPI cells stimulated by LPS

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

Zheng, Wenwen; Zheng, Xuexing; Department of Anesthesiology, University of Miami Miller School of Medicine, Miami, FL 33136

2012-04-20

Highlights: Black-Right-Pointing-Pointer LPS induces proinflammatory cytokine release in HAPI cells. Black-Right-Pointing-Pointer JNK pathway is dependent on TLR4 signaling to release cytokines. Black-Right-Pointing-Pointer NF-{kappa}B pathway is dependent on Nod1 signaling to release cytokines. -- Abstract: A growing body of evidence recently suggests that glial cell activation plays an important role in several neurodegenerative diseases and neuropathic pain. Microglia in the central nervous system express toll-like receptor 4 (TLR4) that is traditionally accepted as the primary receptor of lipopolysaccharide (LPS). LPS activates TLR4 signaling pathways to induce the production of proinflammatory molecules. In the present studies, we verified the LPS signaling pathwaysmore » using cultured highly aggressively proliferating immortalized (HAPI) microglial cells. We found that HAPI cells treated with LPS upregulated the expression of TLR4, phospho-JNK (pJNK) and phospho-NF-{kappa}B (pNF-{kappa}B), TNF{alpha} and IL-1{beta}. Silencing TLR4 with siRNA reduced the expression of pJNK, TNF{alpha} and IL-1{beta}, but not pNF-{kappa}B in the cells. Inhibition of JNK with SP600125 (a JNK inhibitor) decreased the expression of TNF{alpha} and IL-1{beta}. Unexpectedly, we found that inhibition of Nod1 with ML130 significantly reduced the expression of pNF-{kappa}B. Inhibition of NF-{kappa}B also reduced the expression of TNF{alpha} and IL-1{beta}. Nod1 ligand, DAP induced the upregulation of pNF-{kappa}B which was blocked by Nod1 inhibitor. These data indicate that LPS-induced pJNK is TLR4-dependent, and that pNF-{kappa}B is Nod1-dependent in HAPI cells treated with LPS. Either TLR4-JNK or Nod1-NF-{kappa}B pathways is involved in the expression of TNF{alpha} and IL-1{beta}.« less

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.

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.

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

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 selectively target inhibitor of kappaB kinase have potential as antifibrotics.

High resolution mapping and classification of oyster habitats in nearshore Louisiana using sidescan sonar

USGS Publications Warehouse

Allen, Y.C.; Wilson, C.A.; Roberts, H.H.; Supan, J.

2005-01-01

Sidescan sonar holds great promise as a tool to quantitatively depict the distribution and extent of benthic habitats in Louisiana's turbid estuaries. In this study, we describe an effective protocol for acoustic sampling in this environment. We also compared three methods of classification in detail: mean-based thresholding, supervised, and unsupervised techniques to classify sidescan imagery into categories of mud and shell. Classification results were compared to ground truth results using quadrat and dredge sampling. Supervised classification gave the best overall result (kappa = 75%) when compared to quadrat results. Classification accuracy was less robust when compared to all dredge samples (kappa = 21-56%), but increased greatly (90-100%) when only dredge samples taken from acoustically homogeneous areas were considered. Sidescan sonar when combined with ground truth sampling at an appropriate scale can be effectively used to establish an accurate substrate base map for both research applications and shellfish management. The sidescan imagery presented here also provides, for the first time, a detailed presentation of oyster habitat patchiness and scale in a productive oyster growing area.

Solitary necrobiotic xanthogranuloma of an upper extremity in association with multiple myeloma.

PubMed

Bain, E Eugene; Meehan, Shane A; Hale, Elizabeth K

2014-05-01

Necrobiotic xanthogranuloma (NXG) is an uncommon granulomatous disorder of unknown pathogenesis that often presents with yellowish plaques in a periorbital distribution. While a majority of cases are associated with an underlying paraproteinemia of the IgG kappa type, a much smaller number are found to be associated with an underlying multiple myeloma. We present a case of a 78-year-old male with an isolated lesion of NXG on his right upper extremity. Following his diagnosis of NXG, further investigation for underlying systemic disorders with serum immunofixation revealed a monoclonal IgG kappa immunoglobulin with an M-spike of 1.2 g/dL. A PET-CT demonstrated bone destruction in the left proximal fifth rib, left scapula, the anterior lumbar I (L1) vertebrae, the left lumbar III (L3) vertebrae posterior elements and possibly left sacrum. A bone marrow biopsy revealed 18 % plasma cells. With these findings he was diagnosed with stage I multiple myeloma. Though clinically unimpressive and atypical in location for NXG, early biopsy and diagnosis of this solitary lesion led to the discovery of his hematopoietic disorder.

Calculation of site affinity constants and cooperativity coefficients for binding of ligands and/or protons to macromolecules. II. Relationships between chemical model and partition function algorithm.

PubMed

Fisicaro, E; Braibanti, A; Lamb, J D; Oscarson, J L

1990-05-01

The relationships between the chemical properties of a system and the partition function algorithm as applied to the description of multiple equilibria in solution are explained. The partition functions ZM, ZA, and ZH are obtained from powers of the binary generating functions Jj = (1 + kappa j gamma j,i[Y])i tau j, where i tau j = p tau j, q tau j, or r tau j represent the maximum number of sites in sites in class j, for Y = M, A, or H, respectively. Each term of the generating function can be considered an element (ij) of a vector Jj and each power of the cooperativity factor gamma ij,i can be considered an element of a diagonal cooperativity matrix gamma j. The vectors Jj are combined in tensor product matrices L tau = (J1) [J2]...[Jj]..., thus representing different receptor-ligand combinations. The partition functions are obtained by summing elements of the tensor matrices. The relationship of the partition functions with the total chemical amounts TM, TA, and TH has been found. The aim is to describe the total chemical amounts TM, TA, and TH as functions of the site affinity constants kappa j and cooperativity coefficients bj. The total amounts are calculated from the sum of elements of tensor matrices Ll. Each set of indices (pj..., qj..., rj...) represents one element of a tensor matrix L tau and defines each term of the summation. Each term corresponds to the concentration of a chemical microspecies. The distinction between microspecies MpjAqjHrj with ligands bound on specific sites and macrospecies MpAqHR corresponding to a chemical stoichiometric composition is shown. The translation of the properties of chemical model schemes into the algorithms for the generation of partition functions is illustrated with reference to a series of examples of gradually increasing complexity. The equilibria examined concern: (1) a unique class of sites; (2) the protonation of a base with two classes of sites; (3) the simultaneous binding of ligand A and proton H to a macromolecule or receptor M with four classes of sites; and (4) the binding to a macromolecule M of ligand A which is in turn a receptor for proton H. With reference to a specific example, it is shown how a computer program for least-squares refinement of variables kappa j and bj can be organized. The chemical model from the free components M, A, and H to the saturated macrospecies MpAQHR, with possible complex macrospecies MpAq and AHR, is defined first.(ABSTRACT TRUNCATED AT 250 WORDS)

Reliability of injury grading systems for patients with blunt splenic trauma.

PubMed

Olthof, D C; van der Vlies, C H; Scheerder, M J; de Haan, R J; Beenen, L F M; Goslings, J C; van Delden, O M

2014-01-01

The most widely used grading system for blunt splenic injury is the American Association for the Surgery of Trauma (AAST) organ injury scale. In 2007 a new grading system was developed. This 'Baltimore CT grading system' is superior to the AAST classification system in predicting the need for angiography and embolization or surgery. The objective of this study was to assess inter- and intraobserver reliability between radiologists in classifying splenic injury according to both grading systems. CT scans of 83 patients with blunt splenic injury admitted between 1998 and 2008 to an academic Level 1 trauma centre were retrospectively reviewed. Inter and intrarater reliability were expressed in Cohen's or weighted Kappa values. Overall weighted interobserver Kappa coefficients for the AAST and 'Baltimore CT grading system' were respectively substantial (kappa=0.80) and almost perfect (kappa=0.85). Average weighted intraobserver Kappa's values were in the 'almost perfect' range (AAST: kappa=0.91, 'Baltimore CT grading system': kappa=0.81). The present study shows that overall the inter- and intraobserver reliability for grading splenic injury according to the AAST grading system and 'Baltimore CT grading system' are equally high. Because of the integration of vascular injury, the 'Baltimore CT grading system' supports clinical decision making. We therefore recommend use of this system in the classification of splenic injury. Copyright © 2012 Elsevier Ltd. All rights reserved.

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.

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.

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.

Effect of calcium chloride addition on ice cream structure and quality.

PubMed

Costa, F F; Resende, J V; Abreu, L R; Goff, H D

2008-06-01

The influence of calcium fortification by the addition of calcium chloride on quality parameters of ice cream based on physical properties was investigated, as was the effect of kappa-carrageenan at modifying the effects of this calcium fortification. Four ice cream mixes of conventional composition, with added kappa-carrageenan (0 or 0.025%) and added calcium chloride (0 or 4.4 g L(-1) = 40 mM of added Ca(2+)), were prepared. Modulated temperature-differential scanning calorimetry was used to investigate the effect of calcium chloride on the nucleation temperature, enthalpy of melting, and freezing point depression. The protein composition of 15.4% (wt/wt) reconstituted skim milk powder solutions with or without 4.4 g L(-1) added CaCl(2) and in the supernatant after ultracentrifugation was determined. Fat particle size distributions in ice cream were characterized by light scattering. Ice crystal sizes before and after temperature cycling were determined by cold-stage light microscopy. The results demonstrated that the addition of calcium chloride led to a substantial increase in ice crystal sizes and in fat partial coalescence, which were exacerbated by the addition of kappa-carrageenan. These results can be explained by the interaction between Ca(2+) ions and casein micelles, rather than any effects on freezing point depression. The calcium ions led to a more compact micelle, less serum beta-casein, and high fat destabilization, all of which would be expected to reduce macromolecular structure and volume occupancy in the unfrozen phase, which led to increased rates of ice recrystallization.

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...