Science.gov

Sample records for agreement kappa statistic

  1. Assessing agreement with multiple raters on correlated kappa statistics.

    PubMed

    Cao, Hongyuan; Sen, Pranab K; Peery, Anne F; Dellon, Evan S

    2016-07-01

    In clinical studies, it is often of interest to see the diagnostic agreement among clinicians on certain symptoms. Previous work has focused on the agreement between two clinicians under two different conditions or the agreement among multiple clinicians under one condition. Few have discussed the agreement study with a design where multiple clinicians examine the same group of patients under two different conditions. In this paper, we use the intraclass kappa statistic for assessing nominal scale agreement with such a design. We derive an explicit variance formula for the difference of correlated kappa statistics and conduct hypothesis testing for the equality of kappa statistics. Simulation studies show that the method performs well with realistic sample sizes and may be superior to a method that did not take into account the measurement dependence structure. The practical utility of the method is illustrated on data from an eosinophilic esophagitis (EoE) study.

  2. 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.

  3. 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…

  4. 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.

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

    PubMed

    Zhou, Ming; Yang, Zhao

    2014-06-30

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

  6. Dispersion-Weighted Kappa: An Integrative Framework for Metric and Nominal Scale Agreement Coefficients

    ERIC Educational Resources Information Center

    Schuster, Christof; Smith, David A.

    2005-01-01

    The rater agreement literature is complicated by the fact that it must accommodate at least two different properties of rating data: the number of raters (two versus more than two) and the rating scale level (nominal versus metric). While kappa statistics are most widely used for nominal scales, intraclass correlation coefficients have been…

  7. Testing the Difference of Correlated Agreement Coefficients for Statistical Significance

    ERIC Educational Resources Information Center

    Gwet, Kilem L.

    2016-01-01

    This article addresses the problem of testing the difference between two correlated agreement coefficients for statistical significance. A number of authors have proposed methods for testing the difference between two correlated kappa coefficients, which require either the use of resampling methods or the use of advanced statistical modeling…

  8. Kappa statistic for clustered dichotomous responses from physicians and patients.

    PubMed

    Kang, Chaeryon; Qaqish, Bahjat; Monaco, Jane; Sheridan, Stacey L; Cai, Jianwen

    2013-09-20

    The bootstrap method for estimating the standard error of the kappa statistic in the presence of clustered data is evaluated. Such data arise, for example, in assessing agreement between physicians and their patients regarding their understanding of the physician-patient interaction and discussions. We propose a computationally efficient procedure for generating correlated dichotomous responses for physicians and assigned patients for simulation studies. The simulation result demonstrates that the proposed bootstrap method produces better estimate of the standard error and better coverage performance compared with the asymptotic standard error estimate that ignores dependence among patients within physicians with at least a moderately large number of clusters. We present an example of an application to a coronary heart disease prevention study.

  9. Alternative Methods for Calculating Intercoder Reliability in Content Analysis: Kappa, Weighted Kappa and Agreement Charts Procedures.

    ERIC Educational Resources Information Center

    Kang, Namjun

    If content analysis is to satisfy the requirement of objectivity, measures and procedures must be reliable. Reliability is usually measured by the proportion of agreement of all categories identically coded by different coders. For such data to be empirically meaningful, a high degree of inter-coder reliability must be demonstrated. Researchers in…

  10. Experience and grammatical agreement: Statistical learning shapes number agreement production

    PubMed Central

    Haskell, Todd R.; Thornton, Robert; MacDonald, Maryellen C.

    2009-01-01

    A robust result in research on the production of grammatical agreement is that speakers are more likely to produce an erroneous verb with phrases such as the key to the cabinets, with a singular noun followed by a plural one, than with phrases such as the keys to the cabinet, where a plural noun is followed by a singular. These asymmetries are thought to reflect core language production processes. Previous accounts have attributed error patterns to a syntactic number feature present on plurals but not singulars. An alternative approach is presented in which a process similar to structural priming contributes to the error asymmetry via speakers' past experiences with related agreement constructions. A corpus analysis and two agreement production studies test this account. The results suggest that agreement production is shaped by statistical learning from past language experience. Implications for accounts of agreement are discussed. PMID:19942213

  11. Introduction to special section on Origins and Properties of Kappa Distributions: Statistical Background and Properties of Kappa Distributions in Space Plasmas

    NASA Astrophysics Data System (ADS)

    Livadiotis, George

    2015-03-01

    Empirical kappa distributions provide a straightforward replacement of the Maxwell distribution for systems out of thermal equilibrium such as space plasmas. Kappa distributions have become increasingly widespread across space physics with the number of relevant publications following, remarkably, an exponential growth rate. However, a breakthrough in the field came with the connection of kappa distributions with the framework of nonextensive statistical mechanics. This introductory paper clarifies fundamental physical concepts and provides mathematical formulations of the theory of kappa distributions, which are a consequence of the connection of kappa distributions with a solid statistical background. Among others, the paper presents the existence of a consistent definition of temperature in systems out of thermal equilibrium described by kappa distributions, the physical meaning of the kappa index, and the formulation of the kappa distribution of a Hamiltonian. In addition, the paper examines the most frequent values of kappa indices in space plasmas. Statistical analysis reveals trends between the characteristic values of density, temperature, and kappa index of space plasmas. Finally, understanding the kinetic interpretation of the temperature as the mean kinetic energy, and of the kappa index as the correlation of kinetic energies, helps to develop all the possible formulations of isotropic/anisotropic kappa distributions.

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

    PubMed

    Kirilenko, Andrei P; Stepchenkova, Svetlana

    2016-01-01

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

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

    PubMed Central

    Kirilenko, Andrei P.; Stepchenkova, Svetlana

    2016-01-01

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

  14. 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. PMID:25012930

  15. Experience and Grammatical Agreement: Statistical Learning Shapes Number Agreement Production

    ERIC Educational Resources Information Center

    Haskell, Todd R.; Thornton, Robert; MacDonald, Maryellen C.

    2010-01-01

    A robust result in research on the production of grammatical agreement is that speakers are more likely to produce an erroneous verb with phrases such as "the key to the cabinets", with a singular noun followed by a plural one, than with phrases such as "the keys to the cabinet", where a plural noun is followed by a singular. These asymmetries are…

  16. Compressed ultrasound video image-quality evaluation using a Likert scale and Kappa statistical analysis

    NASA Astrophysics Data System (ADS)

    Stewart, Brent K.; Carter, Stephen J.; Langer, Steven G.; Andrew, Rex K.

    1998-06-01

    Experiments using NASA's Advanced Communications Technology Satellite were conducted to provide an estimate of the compressed video quality required for preservation of clinically relevant features for the detection of trauma. Bandwidth rates of 128, 256 and 384 kbps were used. A five point Likert scale (1 equals no useful information and 5 equals good diagnostic quality) was used for a subjective preference questionnaire to evaluate the quality of the compressed ultrasound imagery at the three compression rates for several anatomical regions of interest. At 384 kbps the Likert scores (mean plus or minus SD) were abdomen (4.45 plus or minus 0.71), carotid artery (4.70 plus or minus 0.36), kidney (5.0 plus or minus 0.0), liver (4.67 plus or minus 0.58) and thyroid (4.03 plus or minus 0.74). Due to the volatile nature of the H.320 compressed digital video stream, no statistically significant results can be derived through this methodology. As the MPEG standard has at its roots many of the same intraframe and motion vector compression algorithms as the H.261 (such as that used in the previous ACTS/AMT experiments), we are using the MPEG compressed video sequences to best gauge what minimum bandwidths are necessary for preservation of clinically relevant features for the detection of trauma. We have been using an MPEG codec board to collect losslessly compressed video clips from high quality S- VHS tapes and through direct digitization of S-video. Due to the large number of videoclips and questions to be presented to the radiologists and for ease of application, we have developed a web browser interface for this video visual perception study. Due to the large numbers of observations required to reach statistical significance in most ROC studies, Kappa statistical analysis is used to analyze the degree of agreement between observers and between viewing assessment. If the degree of agreement amongst readers is high, then there is a possibility that the ratings (i

  17. 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…

  18. Kappa as a Parameter of a Symmetry Model for Rater Agreement.

    ERIC Educational Resources Information Center

    Schuster, Christof

    2001-01-01

    If two raters assign targets to categories, the ratings can be arranged in a two-dimensional contingency table. This article presents a model for the frequencies in such a contingency table for which Cohen's kappa is a parameter. Illustrates the model using data from a study of the psychobiology of depression. (Author/SLD)

  19. The Effect of the Raters' Marginal Distributions on Their Matched Agreement: A Rescaling Framework for Interpreting Kappa.

    PubMed

    Karelitz, Tzur M; Budescu, David V

    2013-11-01

    Cohen's κ measures the improvement in classification above chance level and it is the most popular measure of interjudge agreement. Yet, there is considerable confusion about its interpretation. Specifically, researchers often ignore the fact that the observed level of matched agreement is bounded from above and below and the bounds are a function of the particular marginal distributions of the table. We propose that these bounds should be used to rescale the components of κ (observed and expected agreement). Rescaling κ in this manner results in κ', a measure that was originally proposed by Cohen (1960) and was largely ignored in both research and practice. This measure provides a common scale for agreement measures of tables with different marginal distributions. It reaches the maximal value of 1 when the judges show the highest level of agreement possible, given their marginal disagreements. We conclude that κ' should be used to measure the level of matched agreement contingent on a particular set of marginal distributions. The article provides a framework and a set of guidelines that facilitate comparisons between various types of agreement tables. We illustrate our points with simulations and real data from two studies-one involving judges' ratings of baseball players and one involving ratings of essays in high-stakes tests. PMID:26745599

  20. The Effect of the Raters' Marginal Distributions on Their Matched Agreement: A Rescaling Framework for Interpreting Kappa.

    PubMed

    Karelitz, Tzur M; Budescu, David V

    2013-11-01

    Cohen's κ measures the improvement in classification above chance level and it is the most popular measure of interjudge agreement. Yet, there is considerable confusion about its interpretation. Specifically, researchers often ignore the fact that the observed level of matched agreement is bounded from above and below and the bounds are a function of the particular marginal distributions of the table. We propose that these bounds should be used to rescale the components of κ (observed and expected agreement). Rescaling κ in this manner results in κ', a measure that was originally proposed by Cohen (1960) and was largely ignored in both research and practice. This measure provides a common scale for agreement measures of tables with different marginal distributions. It reaches the maximal value of 1 when the judges show the highest level of agreement possible, given their marginal disagreements. We conclude that κ' should be used to measure the level of matched agreement contingent on a particular set of marginal distributions. The article provides a framework and a set of guidelines that facilitate comparisons between various types of agreement tables. We illustrate our points with simulations and real data from two studies-one involving judges' ratings of baseball players and one involving ratings of essays in high-stakes tests.

  1. Examining Agreement and Longitudinal Stability among Traditional and RTI-Based Definitions of Reading Disability Using the Affected-Status Agreement Statistic

    ERIC Educational Resources Information Center

    Waesche, Jessica S. Brown; Schatschneider, Christopher; Maner, Jon K.; Ahmed, Yusra; Wagner, Richard K.

    2011-01-01

    Rates of agreement among alternative definitions of reading disability and their 1- and 2-year stabilities were examined using a new measure of agreement, the affected-status agreement statistic. Participants were 288,114 first through third grade students. Reading measures were "Dynamic Indicators of Basic Early Literacy Skills" Oral Reading…

  2. Robust statistical approaches to assess the degree of agreement of clinical data

    NASA Astrophysics Data System (ADS)

    Grilo, Luís M.; Grilo, Helena L.

    2016-06-01

    To analyze the blood of patients who took vitamin B12 for a period of time, two different medicine measurement methods were used (one is the established method, with more human intervention, and the other method uses essentially machines). Given the non-normality of the differences between both measurement methods, the limits of agreement are estimated using also a non-parametric approach to assess the degree of agreement of the clinical data. The bootstrap resampling method is applied in order to obtain robust confidence intervals for mean and median of differences. The approaches used are easy to apply, running a friendly software, and their outputs are also easy to interpret. In this case study the results obtained with (non)parametric approaches lead us to different statistical conclusions, but the decision whether agreement is acceptable or not is always a clinical judgment.

  3. Statistical methods for conducting agreement (comparison of clinical tests) and precision (repeatability or reproducibility) studies in optometry and ophthalmology.

    PubMed

    McAlinden, Colm; Khadka, Jyoti; Pesudovs, Konrad

    2011-07-01

    The ever-expanding choice of ocular metrology and imaging equipment has driven research into the validity of their measurements. Consequently, studies of the agreement between two instruments or clinical tests have proliferated in the ophthalmic literature. It is important that researchers apply the appropriate statistical tests in agreement studies. Correlation coefficients are hazardous and should be avoided. The 'limits of agreement' method originally proposed by Altman and Bland in 1983 is the statistical procedure of choice. Its step-by-step use and practical considerations in relation to optometry and ophthalmology are detailed in addition to sample size considerations and statistical approaches to precision (repeatability or reproducibility) estimates.

  4. Preferential rearrangement of the immunoglobulin kappa chain joining region J kappa 1 and J kappa 2 segments in mouse spleen DNA.

    PubMed Central

    Nishi, M; Kataoka, T; Honjo, T

    1985-01-01

    The V kappa-KpnI family, which constitutes approximately equal to 36% of mouse kappa chain variable region gene (V kappa) segments, conserves the Kpn I site (G-G-T-A-C-C) at the position corresponding to residues 35-37. Using this cleavage site, we were able to assess the relative recombination frequency of the kappa chain joining region gene (J kappa) segments in mouse spleen DNA. The J kappa 1 and J kappa 2 segments were used 2- to 5-fold more frequently than were the J kappa 4 and J kappa 5 segments. The J kappa 3 segment was shown to be incapable of recombining with the V kappa segment. The relative recombination frequency of the J kappa segments did not change significantly by lipopolysaccharide stimulation of normal mouse spleens. The relative frequency of the J kappa usage was unaltered in immune disorders such as in nude (nu/nu), MRL (lpr/lpr), and BXSB mice. Seven V kappa-KpnI-J kappa 1 clones were isolated, and their nucleotide sequences were determined. Two of them were derived from the identical germ-line V kappa segment but differed in the nucleotide sequence of the V-J junction. The maximal number of V kappa germ-line segments was estimated to be less than 300 by statistical calculation. Images PMID:3931074

  5. Testing Patterned Hypotheses in Multi-Way Contingency Tables Using Weighted Kappa and Weighted Chi Square

    ERIC Educational Resources Information Center

    Ross, Donald C.

    1977-01-01

    The kappa coefficient and the chi square statistic are used as indices of agreement between two judges' ratings of a set of stimuli on a nominal scale. In this article, the logic of these indices is extended to weighted multi-way cases. (Author/JKS)

  6. 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

  7. Rankine-Hugoniot jump conditions incorporating kappa distributions

    NASA Astrophysics Data System (ADS)

    Livadiotis, G.

    2015-12-01

    The effect of kappa distributions on the Rankine-Hugoniot (R-H) jump conditions of space plasma shocks is examined. The challenge is to find the connection between the plasma kappa values upstream and downstream the shock. Several past attempts to connect the upstream/downstream kappa indices were based on ill-defined first physical principles, such as the dependence of the temperature or the thermal pressure on the kappa index. However, the conservation laws of mass, momentum, and energy are independent of the kappa index, thus all different values of kappa are equivalent for describing the known R-H conditions. The upstream/downstream kappa values must be connected through a new physical concept related to the statistical origin of kappa distributions.

  8. Agreement among 2 x 2 Agreement Indices.

    ERIC Educational Resources Information Center

    Conger, Anthony J.; Ward, David G.

    1984-01-01

    Sixteen measures of reliability for two-category nominal scales are compared. Upon correcting for chance agreement, there are only five distinct indices: Fleiss's modification of A-sub-1, the phi coefficient, Cohen's kappa, and two intraclass coefficients. Recommendations for choosing an agreement index are made based on definitions, magnitude,…

  9. KAPPA: Kernel Applications Package

    NASA Astrophysics Data System (ADS)

    Currie, Malcolm J.; Berry, David S.

    2014-03-01

    KAPPA comprising about 180 general-purpose commands for image processing, data visualization, and manipulation of the standard Starlink data format--the NDF. It works with Starlink's various specialized 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. KAPPA uses the Starlink environment (ascl:1110.012).

  10. Observer Agreement for Timed-Event Sequential Data: A Comparison of Time-Based and Event-Based Algorithms

    PubMed Central

    Bakeman, Roger; Quera, Vicenç; Gnisci, Augusto

    2009-01-01

    Observer agreement is often regarded as the sine qua non of observational research. Cohen’s kappa is a widely-used index and is appropriate when discrete entities, such as a turn-of-talk or a demarcated time-interval, are presented to pairs of observers to code. Kappa-like statistics and agreement matrixes are also used for the timed-event sequential data produced when observers first segment and then code events detected in the stream of behavior, noting onset and offset times. Such kappas are of two kinds, time-based and event-based. Available for download is a computer program (OASTES, Observer Agreement for Simulated Timed Event Sequences) that simulates the coding of observers of a stated accuracy, and then computes agreement statistics for two time-based kappas (with and without tolerance) and three event-based kappas (one implemented in The Observer, one in INTERACT, and one in GSEQ). Based on simulation results presented here, and due to the somewhat different information provide by each, reporting of both a time-based and an event-based kappa is recommended. PMID:19182133

  11. 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.

  12. 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

  13. Origins and properties of kappa distributions in space plasmas

    NASA Astrophysics Data System (ADS)

    Livadiotis, George

    2016-07-01

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

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

    ERIC Educational Resources Information Center

    Warrens, Matthijs J.

    2011-01-01

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

  15. A FORTRAN program for computing the exact variance of weighted kappa.

    PubMed

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

    2005-10-01

    An algorithm and associated FORTRAN program are provided for the exact variance of weighted kappa. Program VARKAP provides the weighted kappa test statistic, the exact variance of weighted kappa, a Z score, one-sided lower- and upper-tail N(0,1) probability values, and the two-tail N(0,1) probability value.

  16. The Rho Kappa Spirit

    ERIC Educational Resources Information Center

    McCullagh, Mary T.

    2012-01-01

    Many years ago, Christopher Columbus High School opened a chapter of Rho Kappa, the Social Studies Honor Society developed through the Florida Council for the Social Studies (FCSS). As department chair and member of FCSS, the author was thrilled to be able to offer their students opportunities in the Honor Society for the Social Studies. They…

  17. Measuring statistical agreement between four point of care (POC) lactate meters and a laboratory blood analyzer in cats.

    PubMed

    Acierno, Mark J; Johnson, Meghan E; Eddleman, Lee Ann; Mitchell, Mark A

    2008-04-01

    The use of blood lactate concentrations as a prognostic indicator and therapeutic gauge in feline medicine has been hindered by the inability to obtain values in a timely manner with minimal quantities of blood. Recently, hand-held point-of-care (POC) lactate meters have become commercially available. The objective of this prospective study was to determine if lactate values produced by three commercially available and one medical grade POC meter were in agreement with a laboratory blood analyzer. Blood samples from 47 cats were collected on presentation to an emergency service and processed on four POC meters and a Stat Profile Critical Care Xpress blood analyzer. The results were analyzed using the Bland-Altman method. The blood lactate values produced by the hospital grade POC meter and one of the commercially POC meters were in good agreement with the Critical Care Xpress blood analyzer. Other commercially available POC meters produced acceptable agreement. PMID:17904887

  18. Statistics

    Cancer.gov

    Links to sources of cancer-related statistics, including the Surveillance, Epidemiology and End Results (SEER) Program, SEER-Medicare datasets, cancer survivor prevalence data, and the Cancer Trends Progress Report.

  19. Agreement between insurance claim and self-reported hospital and emergency room utilization data among persons with diabetes.

    PubMed

    Marks, Andrea S; Lee, David W; Slezak, Julie; Berger, Jan; Patel, Hitesh; Johnson, Kenneth E

    2003-01-01

    As part of a retrospective evaluation of a diabetes management program, the agreement between self-reported and insurance claim data on hospitalization and emergency room utilization was examined. Data agreement on hospitalization or emergency room visits between the two collection modes was evaluated through the use of simple agreement proportions and the kappa agreement statistic. A total of 1,230 participant responses were studied. The proportions of patients with hospitalization or emergency room visits were indistinguishable between the self-reported and medical claims data, and kappa statistics also indicated good-to-excellent agreement between data sets. The percentages of participants whose self-reported hospitalization and emergency room utilization exactly matched data derived from insurance claims were high (89.1% and 87.2%, respectively). Furthermore, the kappa statistics of agreement for the number of hospitalizations (0.6366) and emergency room visits (0.5390) indicate good agreement between self-reported and insurance claim data. The results of this study suggest either self-reported or insurance claims data can be used to evaluate the impact of health care interventions on hospital or emergency room utilization.

  20. Agreement between self- and clinician-collected specimen results for detection and typing of high-risk human papillomavirus in specimens from women in Gugulethu, South Africa.

    PubMed

    Jones, Heidi E; Allan, Bruce R; van de Wijgert, Janneke H H M; Altini, Lydia; Taylor, Sylvia M; de Kock, Alana; Coetzee, Nicol; Williamson, Anna-Lise

    2007-06-01

    We assessed the agreement in detection of high-risk human papillomavirus (HPV), as well as specific HPV types, between self- and clinician-obtained specimens for 450 women over 18 years of age attending a community health center in Gugulethu, South Africa. Both self-collected swabs and tampons had high agreement with clinician-obtained brushes when the Roche Reverse Line Blot Assay (RLBA) was used (for swabs, 86% concordance, with a kappa statistic [kappa] of 0.71; for tampons, 89% concordance, with kappa of 0.75). Agreement was lower, although still fair, with the Digene Hybrid Capture 2 test (HC2), with kappa higher for swabs than for tampons (for swabs, 81% concordance, with kappa of 0.61; for tampons, 82% concordance, with kappa of 0.55). Low-risk HPV types were nearly two times more common in self-collected specimens than in clinician-collected specimens tested by RLBA. All 15 women diagnosed with high-grade lesions by cytology tested positive for high-risk HPV with clinician-collected specimens tested by RLBA and HC2, while 11 out of 15 tested positive with self-collected specimens by HC2 and 5 out of 6 tested positive by RLBA. Self-collected specimens can provide valid specimens for HPV testing using nucleic acid amplification tests, although a few cytological abnormalities may be missed.

  1. Cohen's weighted kappa with Turbo Pascal (FORTRAN).

    PubMed

    Reed, J F; Reed, J J

    1992-07-01

    A microcomputer based Turbo Pascal and FORTRAN program for Cohen's weighted kappa (kappa w) is given. Three clinical applications for kappa w are also presented. A typical data file, the Pascal and FORTRAN program listing and corresponding output are given.

  2. Modeling agreement on categorical scales in the presence of random scorers.

    PubMed

    Vanbelle, Sophie; Lesaffre, Emmanuel

    2016-01-01

    Kappa coefficients are often used to assess agreement between two fixed scorers on categorical scales. Cohen's version is popular for nominal scales and the weighted version for ordinal scales. In the present paper, similar agreement coefficients are defined for random scorers. A partial-Bayesian methodology is then developed to directly relate these agreement coefficients to predictors through a multilevel model. Statistical properties of the proposed approach are studied using simulations. Finally, the approach is applied to gynecological and medical imaging data. PMID:26395905

  3. Restricted kappa chain expression in early ontogeny: biased utilization of V kappa exons and preferential V kappa-J kappa recombinations

    PubMed Central

    1993-01-01

    To determine the extent of kappa chain diversity in the preimmune repertoire early in development, kappa cDNA libraries were analyzed from 15-d old fetal omentum, 18-d-old fetal liver, and 3-wk old bone marrow. An anchored polymerase chain reaction approach was used to avoid bias for particular V kappa families. From the sequence analysis of 27 bone marrow clones, 10 different families and 20 unique V kappa genes were identified. In contrast, the V kappa expression in the fetus is highly restricted and clearly differs from the broader distribution see in 3-wk-old bone marrow. Although several V kappa families were represented in the fetal library including V kappa 9, V kappa 10, V kappa 4,5, V kappa 8, and V kappa 1, one or two members of individual families were observed repeatedly. The fetal liver and omentum libraries were found to be largely overlapping. Given the V kappa families/exons identified in the fetal sequences, the mechanism of kappa rearrangements in the early repertoire appears to occur predominantly by inversion. Importantly, the fetal repertoire was further restricted by dominant V kappa-J kappa combinations such as V kappa 4,5-J kappa 5, V kappa 9-J kappa 4, and V kappa 10-J kappa 1. Since in some cases independent rearrangements could be established, the results indicate a bias for particular V kappa-J kappa joins. The results also suggest that clonal expansion/selection in the fetal repertoire takes place after light chain rearrangement as opposed to at the pre-B cell level in the bone marrow. The restriction observed in kappa light chain expression together with known restrictions in gene usage and junctional diversity at the heavy chain level indicate a remarkably conserved fetal repertoire. PMID:8478611

  4. Some common errors of experimental design, interpretation and inference in agreement studies.

    PubMed

    Erdmann, T P; De Mast, J; Warrens, M J

    2015-12-01

    We signal and discuss common methodological errors in agreement studies and the use of kappa indices, as found in publications in the medical and behavioural sciences. Our analysis is based on a proposed statistical model that is in line with the typical models employed in metrology and measurement theory. A first cluster of errors is related to nonrandom sampling, which results in a potentially substantial bias in the estimated agreement. Second, when class prevalences are strongly nonuniform, the use of the kappa index becomes precarious, as its large partial derivatives result in typically large standard errors of the estimates. In addition, the index reflects rather one-sidedly in such cases the consistency of the most prevalent class, or the class prevalences themselves. A final cluster of errors concerns interpretation pitfalls, which may lead to incorrect conclusions based on agreement studies. These interpretation issues are clarified on the basis of the proposed statistical modelling. The signalled errors are illustrated from actual studies published in prestigious journals. The analysis results in a number of guidelines and recommendations for agreement studies, including the recommendation to use alternatives to the kappa index in certain situations.

  5. Nuclear factor-kappaB (NF-kappaB) and cyclooxygenase-2 (COX-2) expression in the oral mucosa following cancer chemotherapy.

    PubMed

    Logan, Richard M; Gibson, Rachel J; Sonis, Stephen T; Keefe, Dorothy M K

    2007-04-01

    Oral mucositis is a serious and debilitating side effect of cancer treatment. Greater understanding of the pathobiology of mucositis has recently led to the advent of targeted treatments for specific patient populations; however the treatment for mucositis remains palliative for most patients. Nuclear factor-kappaB (NF-kappaB) and cyclooxygenase 2 (COX-2) are thought to play important roles in the development of mucositis. In this study, 20 patients undergoing cytotoxic chemotherapy had oral mucosal biopsies taken prior to and following administration of cytotoxic chemotherapy. The samples were stained for NF-kappaB and COX-2 using routine immunohistochemistry. The results from this preliminary study demonstrated statistically significant increased oral mucosal staining for NF-kappaB and COX-2 following cytotoxic chemotherapy and provide further support for the role of NF-kappaB and COX-2 in the pathogenesis of mucositis. PMID:16979925

  6. Agreement between Two Independent Groups of Raters

    ERIC Educational Resources Information Center

    Vanbelle, Sophie; Albert, Adelin

    2009-01-01

    We propose a coefficient of agreement to assess the degree of concordance between two independent groups of raters classifying items on a nominal scale. This coefficient, defined on a population-based model, extends the classical Cohen's kappa coefficient for quantifying agreement between two raters. Weighted and intraclass versions of the…

  7. Classifying sea lamprey marks on Great Lakes lake trout: observer agreement, evidence on healing times between classes and recommendations for reporting of marking statistics

    USGS Publications Warehouse

    Ebener, Mark P.; Bence, James R.; Bergstedt, Roger A.; Mullet, Katherine M.

    2003-01-01

    In 1997 and 1998 two workshops were held to evaluate how consistent observers were at classifying sea lamprey (Petromyzon marinus) marks on Great Lakes lake trout (Salvelinus namaycush) as described in the King classification system. Two trials were held at each workshop, with group discussion between trials. Variation in counting and classifying marks was considerable, such that reporting rates for A1–A3 marks varied two to three-fold among observers of the same lake trout. Observer variation was greater for classification of healing or healed marks than for fresh marks. The workshops highlighted, as causes for inconsistent mark classification, both departures from the accepted protocol for classifying marks by some agencies, and differences in how sliding and multiple marks were interpreted. Group discussions led to greater agreement in classifying marks. We recommend ways to improve the reliability of marking statistics, including the use of a dichotomous key to classify marks. Laboratory data show that healing times of marks on lake trout were much longer at 4°C and 1°C than at 10°C and varied greatly among individuals. Reported A1–A3 and B1–B3 marks observed in late summer and fall collections likely result from a mixture of attacks by two year classes of sea lamprey. It is likely that a substantial but highly uncertain proportion of attacks that occur in late summer and fall lead to marks that are classified as A1–A3 the next spring. We recommend additional research on mark stage duration.

  8. Meeting U.S. Healthy People 2010 Levels of Physical Activity: Agreement of 2 Measures across 2 years

    PubMed Central

    Dishman, Rod K.; Rooks, Cherie R.; Thom, Nathaniel J.; Motl, Robert W.; Nigg, Claudio R.

    2010-01-01

    Background Measuring the way people vary across time in meeting recommended levels of physical activity should be a fundamental component of public health surveillance. However, we were unaware of prospective cohort studies that had examined this in a population base using convergent measures. Purpose We examined agreement between two validated measures used to estimate periodic change in the rate of meeting U.S. Healthy People 2010 guidelines for participation in moderate or vigorous physical activity. Methods A cohort (N=497) from a random, multi-ethnic sample of adults living in Hawaii was assessed every 6-months for 2 years starting spring 2004. Latent transition analysis classified people as meeting or not meeting the guidelines. Intra-class kappa statistics and multinomial logistic regression analysis were used to evaluate agreement. Results Agreement for classifying stable classes of people who met or did not meet the guideline each time was substantial for vigorous activity (kappa ∼ .65 - .70) but fair-to-moderate for moderate activity (kappa ∼ .38 - .48). Agreement was poorer for classifying people who transitioned between meeting and not meeting the vigorous guideline (kappa ∼ .45) or the moderate guideline (kappa ∼ .21 - .29). Conclusion Rates of meeting the guidelines varied across time and were estimated differently by the two measures, especially for moderate activity. This illustrates an understudied problem for public health promotion. Accurate classification of change within people is necessary for determining exposure in outcome studies, personal determinants of sufficient activity, and for evaluating whether interventions are successful in sustaining increases in rates of meeting physical activity guidelines. PMID:20538194

  9. Agreement between TOAST and CCS ischemic stroke classification

    PubMed Central

    McArdle, Patrick F.; Kittner, Steven J.; Ay, Hakan; Brown, Robert D.; Meschia, James F.; Rundek, Tatjana; Wassertheil-Smoller, Sylvia; Woo, Daniel; Andsberg, Gunnar; Biffi, Alessandro; Brenner, David A.; Cole, John W.; Corriveau, Roderick; de Bakker, Paul I.W.; Delavaran, Hossein; Dichgans, Martin; Grewal, Raji P.; Gwinn, Katrina; Huq, Mohammed; Jern, Christina; Jimenez-Conde, Jordi; Jood, Katarina; Kaplan, Robert C.; Katschnig, Petra; Katsnelson, Michael; Labovitz, Daniel L.; Lemmens, Robin; Li, Linxin; Lindgren, Arne; Markus, Hugh S.; Peddareddygari, Leema R.; Pedersén, Annie; Pera, Joanna; Redfors, Petra; Roquer, Jaume; Rosand, Jonathan; Rost, Natalia S.; Rothwell, Peter M.; Sacco, Ralph L.; Sharma, Pankaj; Slowik, Agnieszka; Sudlow, Cathie; Thijs, Vincent; Tiedt, Steffen; Valenti, Raffaella

    2014-01-01

    Objective: The objective of this study was to assess the level of agreement between stroke subtype classifications made using the Trial of Org 10172 Acute Stroke Treatment (TOAST) and Causative Classification of Stroke (CCS) systems. Methods: Study subjects included 13,596 adult men and women accrued from 20 US and European genetic research centers participating in the National Institute of Neurological Disorders and Stroke (NINDS) Stroke Genetics Network (SiGN). All cases had independently classified TOAST and CCS stroke subtypes. Kappa statistics were calculated for the 5 major ischemic stroke subtypes common to both systems. Results: The overall agreement between TOAST and CCS was moderate (agreement rate, 70%; κ = 0.59, 95% confidence interval [CI] 0.58–0.60). Agreement varied widely across study sites, ranging from 28% to 90%. Agreement on specific subtypes was highest for large-artery atherosclerosis (κ = 0.71, 95% CI 0.69–0.73) and lowest for small-artery occlusion (κ = 0.56, 95% CI 0.54–0.58). Conclusion: Agreement between TOAST and CCS diagnoses was moderate. Caution is warranted when comparing or combining results based on the 2 systems. Replication of study results, for example, genome-wide association studies, should utilize phenotypes determined by the same classification system, ideally applied in the same manner. PMID:25261504

  10. Agreement on the Level Selection in Laminoplasty among Experienced Surgeons: A Survey-Based Study

    PubMed Central

    Cho, Jae Hwan; Suk, Kyung-Soo; Park, Jong-Beom; Ha, Jung-Ki; Hwang, Chang Ju; Lee, Choon Sung

    2016-01-01

    Study Design Survey based study. Purpose To assess the degree of agreement in level selection of laminoplasty (LP) for the selected cervical myeloradiculopathy cases between experienced spine surgeons. Overview of Literature Although, cervical LP is a widely used surgical technique for multi-level spinal cord compression, until now there is no consensus about how many segments or which segments should be opened to achieve a satisfactory decompression. Methods Thorough clinical and radiographic data (plain X-ray, computed tomography, and magnetic resonance imaging) of 30 patients who had cervical myelopathy were prepared. The data were provided to three independent spine surgeons with over 10 years experience in operation of their own practices. They were questioned about the most preferable surgical method and suitable decompression levels. The second survey was carried out after 6 months with the same cases. If the level difference between respondents was a half level or below, agreement was considered acceptable. The intraobserver and interobserver agreements in level selection were assessed by kappa statistics. Results Three respondents selected LP as an option for 6, 8, and 22 cases in the first survey and 10, 21, and 24 cases in the second survey. The reasons for selection of LP were levels of ossification of the posterior longitudinal ligament (p=0.004), segmental kyphotic deformity (p=0.036) and mean compression score (p=0.041). Intraobserver agreement showed variable results. Interobserver agreement was poor to fair by perfect matching (kappa=0.111–0.304) and fair to moderate by acceptable matching (kappa=0.308–0.625). Conclusions The degree of agreement for level selection of LP was not high even though experienced surgeons would choose the opening segments on the basis of same criteria. These results suggest that more specific guidelines in determination of levels for LP should be required to decrease unnecessary wide decompression according to

  11. Characterizing Observations of Cometary Electrons with Kappa Distributions

    NASA Astrophysics Data System (ADS)

    Broiles, T. W.; Livadiotis, G.; Burch, J. L.; Goldstein, R.; Mandt, K.; Goldstein, J.; Clark, G. B.; Fuselier, S. A.; Samara, M.; Cravens, T.; Eriksson, A. I.; Pierre, H.; Mokashi, P.; Chae, K.

    2015-12-01

    The Rosetta spacecraft arrived at the comet 67P/Churyumov-Gerasimenko on August 6, 2014. Since that time, Rosetta's Ion and Electron Sensor (IES) has made near continuous measurements of the ions and electrons between 4.1 eV/q to 18.3 keV/q. Electron observations are of particular interest, because the electron distributions are highly variable in both temperature and density. At the comet, the thermal and non-thermal electron populations are non-Maxwellian, and the low-energy population has been previously described as a flat-top distribution. Here, we characterize the electrons near the comet as two kappa distributions. The kappa distribution improves upon previous work because it relates the distribution back to statistical properties such as density and temperature. Additionally, the kappa distribution allows us to determine the electron population's departure from thermal equilibrium, which has never been studied at a comet. We find that both the low-energy and high-energy electron populations are well characterized by a kappa distribution. Moreover, the low-energy population varies on the time scale of minutes, which suggest a rapidly changing magnetic connection of the spacecraft to the low-energy electron source region.

  12. Measurement of the Parameter Kappa, and Reevaluation of Kappa for Small to Moderate Earthquakes at Seismic Stations in the Vicinity of Yucca Mountain, Nevada

    SciTech Connect

    Biasi, Glenn; Anderson, John G

    2007-12-05

    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 result 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

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

    SciTech Connect

    Lee, Sang-Myeong; Kleiboeker, Steven B. . E-mail: KleiboekerS@Missouri.edu

    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. Degradation 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.

  14. Echocardiographic agreement in the diagnostic evaluation for infective endocarditis.

    PubMed

    Lauridsen, Trine Kiilerich; Selton-Suty, Christine; Tong, Steven; Afonso, Luis; Cecchi, Enrico; Park, Lawrence; Yow, Eric; Barnhart, Huiman X; Paré, Carlos; Samad, Zainab; Levine, Donald; Peterson, Gail; Stancoven, Amy Butler; Johansson, Magnus Carl; Dickerman, Stuart; Tamin, Syahidah; Habib, Gilbert; Douglas, Pamela S; Bruun, Niels Eske; Crowley, Anna Lisa

    2016-07-01

    Echocardiography is essential for the diagnosis and management of infective endocarditis (IE). However, the reproducibility for the echocardiographic assessment of variables relevant to IE is unknown. Objectives of this study were: (1) To define the reproducibility for IE echocardiographic variables and (2) to describe a methodology for assessing quality in an observational cohort containing site-interpreted data. IE reproducibility was assessed on a subset of echocardiograms from subjects enrolled in the International Collaboration on Endocarditis registry. Specific echocardiographic case report forms were used. Intra-observer agreement was assessed from six site readers on ten randomly selected echocardiograms. Inter-observer agreement between sites and an echocardiography core laboratory was assessed on a separate random sample of 110 echocardiograms. Agreement was determined using intraclass correlation (ICC), coverage probability (CP), and limits of agreement for continuous variables and kappa statistics (κweighted) and CP for categorical variables. Intra-observer agreement for LVEF was excellent [ICC = 0.93 ± 0.1 and all pairwise differences for LVEF (CP) were within 10 %]. For IE categorical echocardiographic variables, intra-observer agreement was best for aortic abscess (κweighted = 1.0, CP = 1.0 for all readers). Highest inter-observer agreement for IE categorical echocardiographic variables was obtained for vegetation location (κweighted = 0.95; 95 % CI 0.92-0.99) and lowest agreement was found for vegetation mobility (κweighted = 0.69; 95 % CI 0.62-0.86). Moderate to excellent intra- and inter-observer agreement is observed for echocardiographic variables in the diagnostic assessment of IE. A pragmatic approach for determining echocardiographic data reproducibility in a large, multicentre, site interpreted observational cohort is feasible.

  15. Interobserver Agreement on Pathologic Features of Liver Biopsy Tissue in Patients with Nonalcoholic Fatty Liver Disease

    PubMed Central

    Jung, Eun Sun; Lee, Kyoungbun; Yu, Eunsil; Kang, Yun Kyung; Cho, Mee-Yon; Kim, Joon Mee; Moon, Woo Sung; Jeong, Jin Sook; Park, Cheol Keun; Park, Jae-Bok; Kang, Dae Young; Sohn, Jin Hee; Jin, So-Young

    2016-01-01

    Background: The histomorphologic criteria for the pathological features of liver tissue from patients with non-alcoholic fatty liver disease (NAFLD) remain subjective, causing confusion among pathologists and clinicians. In this report, we studied interobserver agreement of NAFLD pathologic features and analyzed causes of disagreement. Methods: Thirty-one cases of clinicopathologically diagnosed NAFLD from 10 hospitals were selected. One hematoxylin and eosin and one Masson’s trichrome-stained virtual slide from each case were blindly reviewed with regard to 12 histological parameters by 13 pathologists in a gastrointestinal study group of the Korean Society of Pathologists. After the first review, we analyzed the causes of disagreement and defined detailed morphological criteria. The glass slides from each case were reviewed a second time after a consensus meeting. The degree of interobserver agreement was determined by multi-rater kappa statistics. Results: Kappa values of the first review ranged from 0.0091–0.7618. Acidophilic bodies (k = 0.7618) and portal inflammation (k = 0.5914) showed high levels of agreement, whereas microgranuloma (k = 0.0984) and microvesicular fatty change (k = 0.0091) showed low levels of agreement. After the second review, the kappa values of the four major pathological features increased from 0.3830 to 0.5638 for steatosis grade, from 0.1398 to 0.2815 for lobular inflammation, from 0.1923 to 0.3362 for ballooning degeneration, and from 0.3303 to 0.4664 for fibrosis. Conclusions: More detailed histomorphological criteria must be defined for correct diagnosis and high interobserver agreement of NAFLD. PMID:27086596

  16. Agreement on intimate partner violence among a sample of blue-collar couples.

    PubMed

    Cunradi, Carol B; Bersamin, Melina; Ames, Genevieve

    2009-04-01

    This study assessed agreement level about the occurrence of past-year male-to-female partner violence (MFPV) and female-to-male partner violence (FMPV) among a sample of 897 blue-collar couples. Intimate partner violence (IPV) was measured with the Physical Assault subscale of the revised Conflict Tactics Scales (CTS2). Agreement level was assessed with Cohen's kappa statistic. Lower-bound estimates (based on couple agreement that an IPV event occurred) and upper-bound estimates (based on uncorroborated reports from either partner that an IPV event occurred) were calculated. Results indicated low agreement for most IPV behaviors (kappa < .40). Estimated lower- and upper-bound rates for MFPV were 6.7% and 21.2%, for FMPV, 7.1% and 24.2%, and for any IPV, 10.1% and 30.2%. Findings suggest that single-point IPV prevalence estimates are biased; lower- and upper-bound estimates using collateral reports should be calculated when possible. In addition, findings underscore the importance of conducting IPV research among understudied populations, such as working-class couples, that may be at elevated IPV risk.

  17. Spectrum bias, a common unrecognised issue in orthopaedic agreement studies

    PubMed Central

    Kleinlugtenbelt, Y. V.; Hoekstra, M.; Ham, S. J.; Kloen, P.; Haverlag, R.; Simons, M. P.; Bhandari, M.; Goslings, J. C.; Poolman, R. W.; Scholtes, V. A. B.

    2015-01-01

    Objectives Current studies on the additional benefit of using computed tomography (CT) in order to evaluate the surgeons’ agreement on treatment plans for fracture are inconsistent. This inconsistency can be explained by a methodological phenomenon called ‘spectrum bias’, defined as the bias inherent when investigators choose a population lacking therapeutic uncertainty for evaluation. The aim of the study is to determine the influence of spectrum bias on the intra-observer agreement of treatment plans for fractures of the distal radius. Methods Four surgeons evaluated 51 patients with displaced fractures of the distal radius at four time points: T1 and T2: conventional radiographs; T3 and T4: radiographs and additional CT scan (radiograph and CT). Choice of treatment plan (operative or non-operative) and therapeutic certainty (five-point scale: very uncertain to very certain) were rated. To determine the influence of spectrum bias, the intra-observer agreement was analysed, using Kappa statistics, for each degree of therapeutic certainty. Results In cases with high therapeutic certainty, intra-observer agreement based on radiograph was almost perfect (0.86 to 0.90), but decreased to moderate based on a radiograph and CT (0.47 to 0.60). In cases with high therapeutic uncertainty, intra-observer agreement was slight at best (-0.12 to 0.19), but increased to moderate based on the radiograph and CT (0.56 to 0.57). Conclusion Spectrum bias influenced the outcome of this agreement study on treatment plans. An additional CT scan improves the intra-observer agreement on treatment plans for a fracture of the distal radius only when there is therapeutic uncertainty. Reporting and analysing intra-observer agreement based on the surgeon’s level of certainty is an appropriate method to minimise spectrum bias. Cite this article: Bone Joint Res 2015;4:190–194. PMID:26625876

  18. Agreement and concordance between married couples regarding family planning utilization and fertility intention in Dukem, Ethiopia

    PubMed Central

    2013-01-01

    Background Traditionally, women have been the main respondents for most of knowledge, attitude and practice survey related to family planning and fertility intention. However it is not well known how responses of women about husbands reflect the husband’s attitude and practices. Thus this study is conducted to examine agreement of wife and husband regarding family planning use and fertility desire in Dukem, Ethiopia. Methods A community based cross sectional survey was conducted on 422 married couple’s in Dukem town, central Ethiopia which were selected by using systematic sampling method. The study was conducted from November, 2010 to December, 2010. Data pertaining to fertility intentions and contraception was collected and the level of agreement (kappa statistics) between husbands and wives was computed. Result The observed concordance was 71.6% for ideal family size, 94.9% for contraceptive attitude, 95.9% for fertility desire, and 99.7% for report of number of currently living children. The unadjusted kappa statistic varied from 0.61(p<=0.000) for contraceptive attitude to high of 0.99(P<=0.000) for number of living children, for ideal family size 0.63(P<=0.000), fertility desire 0.91(P<=0.000), ever use of contraceptive 0.84(P<=0.000) and current use of contraceptive 0.87(P<=0.000) having kappa values in between. Overall greater degree of agreement was observed for reproductive health events as compared to family planning attitudes and intentions. Conclusion In surveys pertaining to reproductive health events, the wife’s response may be taken as proxy for the couple’s response, but for assessing family planning attitudes and intentions, may require collecting information from husbands and wives separately. PMID:24079530

  19. Characterization and visualization of rat and guinea pig brain. kappa. opioid receptors: Evidence for. kappa. sub 1 and. kappa. sub 2 opioid receptors

    SciTech Connect

    Zukin, R.S.; Eghbali, M.; Olive, D.; Unterwald, E.M.; Tempel, A. )

    1988-06-01

    {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 were 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.

  20. The zinc finger domain of NEMO is selectively required for NF-kappa B activation by UV radiation and topoisomerase inhibitors.

    PubMed

    Huang, Tony T; Feinberg, Shelby L; Suryanarayanan, Sainath; Miyamoto, Shigeki

    2002-08-01

    Exposure of mammalian cells to UV radiation was proposed to stimulate the transcription factor NF-kappa B by a unique mechanism. Typically, rapid and strong inducers of NF-kappa B, such as tumor necrosis factor alpha (TNF-alpha) and bacterial lipopolysaccharide (LPS), lead to rapid phosphorylation and proteasomal degradation of its inhibitory protein, I kappa B alpha. In contrast, UV, a relatively slower and weaker inducer of NF-kappa B, was suggested not to require phosphorylation of I kappa B alpha for its targeted degradation by the proteasome. We now provide evidence to account for this peculiar degradation process of I kappa B alpha. The phospho-I kappa B alpha generated by UV is only detectable by expressing a Delta F-box mutant of the ubiquitin ligase beta-TrCP, which serves as a specific substrate trap for serine 32 and 36 phosphorylated I kappa B alpha. In agreement with this finding, we also find that the I kappa B kinase (IKK) phospho-acceptor sites on I kappa B alpha, core components of the IKK signalsome, and IKK catalytic activity are all required for UV signaling. Furthermore, deletion and point mutation analyses reveal that both the amino-terminal IKK-binding and the carboxy-terminal putative zinc finger domains of NEMO (IKK gamma) are critical for UV-induced NF-kappa B activation. Interestingly, the zinc finger domain is also required for NF-kappa B activation by two other slow and weak inducers, camptothecin and etoposide. In contrast, the zinc finger module is largely dispensable for NF-kappa B activation by the rapid and strong inducers LPS and TNF-alpha. Thus, we suggest that the zinc finger domain of NEMO likely represents a point of convergence for signaling pathways initiated by slow and weak NF-kappa B-activating conditions.

  1. PROPOV-K: a FORTRAN program for computing a kappa coefficient using a proportional overlap procedure.

    PubMed

    Ahn, C W; Mezzich, J E

    1989-10-01

    The computer program PROPOV-K allows the computation of an unweighted kappa coefficient for expressing interrater agreement in the general case in which multiple raters (not necessarily fixed in number) formulate a variable number of multiple diagnoses for each subject. PROPOV-K assesses agreement among lists of multiple diagnoses composed of nonordered categories. PROPOV-K calculates a kappa coefficient on the basis of estimating proportion of agreement between two diagnostic formulations as the ratio of the number of agreements between specific categories over the number of different specific categories mentioned in the two diagnostic lists. When multiple raters formulate a variable number of multiple diagnoses for each subject, the use of a kappa coefficient has been limited to researchers since there are no generally available computer programs. The purpose of this paper is to present a FORTRAN computer program allowing the computation of a kappa coefficient for the case mentioned above and to illustrate its use with examples respectively involving multiple psychiatric and multiple physical diagnoses.

  2. Rater Agreement on Interpersonal Psychotherapy Problem Areas

    PubMed Central

    Markowitz, John C.; Leon, Andrew C.; Miller, Nina L.; Cherry, Sabrina; Clougherty, Kathleen F.; Villalobos, Liliana

    2000-01-01

    There has been much outcome research on interpersonal psychotherapy (IPT) but little investigation of its components. This study assessed interrater reliability of IPT therapists in identifying interpersonal problem areas and treatment foci from audiotapes of initial treatment sessions. Three IPT research psychotherapists assessed up to 18 audiotapes of dysthymic patients, using the Interpersonal Problem Area Rating Scale. Cohen's kappa was used to examine concordance between raters. Kappas for presence or absence of each of the four IPT problem areas were 0.87 (grief), 0.58 (role dispute), 1.0 (role transition), and 0.48 (interpersonal deficits). Kappa for agreement on a clinical focus was 0.82. IPT therapists agreed closely in rating problem areas and potential treatment foci, providing empirical support for potential therapist consistency in this treatment approach. PMID:10896737

  3. Rater agreement on interpersonal psychotherapy problem areas.

    PubMed

    Markowitz, J C; Leon, A C; Miller, N L; Cherry, S; Clougherty, K F; Villalobos, L

    2000-01-01

    There has been much outcome research on interpersonal psychotherapy (IPT) but little investigation of its components. This study assessed interrater reliability of IPT therapists in identifying interpersonal problem areas and treatment foci from audiotapes of initial treatment sessions. Three IPT research psychotherapists assessed up to 18 audiotapes of dysthymic patients, using the Interpersonal Problem Area Rating Scale. Cohen's kappa was used to examine concordance between raters. Kappas for presence or absence of each of the four IPT problem areas were 0.87 (grief), 0.58 (role dispute), 1.0 (role transition), and 0.48 (interpersonal deficits). Kappa for agreement on a clinical focus was 0.82. IPT therapists agreed closely in rating problem areas and potential treatment foci, providing empirical support for potential therapist consistency in this treatment approach. PMID:10896737

  4. Detecting Prediabetes and Diabetes: Agreement between Fasting Plasma Glucose and Oral Glucose Tolerance Test in Thai Adults

    PubMed Central

    Aekplakorn, Wichai; Tantayotai, Valla; Numsangkul, Sakawduan; Sripho, Wilarwan; Tatsato, Nutchanat; Burapasiriwat, Tuanjai; Pipatsart, Rachada; Sansom, Premsuree; Luckanajantachote, Pranee; Chawarokorn, Pongpat; Thanonghan, Anek; Lakhamkaew, Watchira; Mungkung, Aungsumalin; Boonkean, Rungnapa; Chantapoon, Chanidsa; Kungsri, Mayuree; Luanseng, Kasetsak; Chaiyajit, Kornsinun

    2015-01-01

    Aim. To evaluate an agreement in identifying dysglycemia between fasting plasma glucose (FPG) and the 2 hr postprandial glucose tolerance test (OGTT) in a population with high risk of diabetes. Methods. A total of 6,884 individuals aged 35–65 years recruited for a community-based diabetes prevention program were tested for prediabetes including impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), and diabetes. The agreement was assessed by Kappa statistics. Logistic regression was used to examine factors associated with missed prediabetes and diabetes by FPG. Results. A total of 2671 (38.8%) individuals with prediabetes were identified. The prevalence of prediabetes identified by FPG and OGTT was 32.2% and 22.3%, respectively. The proportions of diabetes classified by OGTT were two times higher than those identified by FPG (11.0% versus 5.4%, resp.). The Kappa statistics for agreement of both tests was 0.55. Overall, FPG missed 46.3% of all prediabetes and 54.7% of all diabetes cases. Prediabetes was more likely to be missed by FPG among female, people aged <45 yrs, and those without family history of diabetes. Conclusion. The detection of prediabetes and diabetes using FPG only may miss half of the cases. Benefit of adding OGTT to FPG in some specific groups should be confirmed. PMID:26347060

  5. Nonlinear evolution of the electromagnetic electron-cyclotron instability in bi-Kappa distributed plasma

    NASA Astrophysics Data System (ADS)

    Eliasson, B.; Lazar, M.

    2015-06-01

    This paper presents a numerical study of the linear and nonlinear evolution of the electromagnetic electron-cyclotron (EMEC) instability in a bi-Kappa distributed plasma. Distributions with high energy tails described by the Kappa power-laws are often observed in collision-less plasmas (e.g., solar wind and accelerators), where wave-particle interactions control the plasma thermodynamics and keep the particle distributions out of Maxwellian equilibrium. Under certain conditions, the anisotropic bi-Kappa distribution gives rise to plasma instabilities creating low-frequency EMEC waves in the whistler branch. The instability saturates nonlinearly by reducing the temperature anisotropy until marginal stability is reached. Numerical simulations of the Vlasov-Maxwell system of equations show excellent agreement with the growth-rate and real frequency of the unstable modes predicted by linear theory. The wave-amplitude of the EMEC waves at nonlinear saturation is consistent with magnetic trapping of the electrons.

  6. Nonlinear evolution of the electromagnetic electron-cyclotron instability in bi-Kappa distributed plasma

    SciTech Connect

    Eliasson, B.; Lazar, M.

    2015-06-15

    This paper presents a numerical study of the linear and nonlinear evolution of the electromagnetic electron-cyclotron (EMEC) instability in a bi-Kappa distributed plasma. Distributions with high energy tails described by the Kappa power-laws are often observed in collision-less plasmas (e.g., solar wind and accelerators), where wave-particle interactions control the plasma thermodynamics and keep the particle distributions out of Maxwellian equilibrium. Under certain conditions, the anisotropic bi-Kappa distribution gives rise to plasma instabilities creating low-frequency EMEC waves in the whistler branch. The instability saturates nonlinearly by reducing the temperature anisotropy until marginal stability is reached. Numerical simulations of the Vlasov-Maxwell system of equations show excellent agreement with the growth-rate and real frequency of the unstable modes predicted by linear theory. The wave-amplitude of the EMEC waves at nonlinear saturation is consistent with magnetic trapping of the electrons.

  7. Diagnostic agreement of conventional and inverted scanned panoramic radiographs in the detection of the mandibular canal and the mental foramen.

    PubMed

    Sakakura, Celso Eduardo; Loffredo, Leonor de Castro Monteiro; Scaf, Gulnara

    2004-01-01

    The aim of this study was to evaluate the diagnostic agreement of conventional panoramic radiographs and their inverted scanned images in the detection of the mandibular canal and mental foramen. A total of 77 panoramic radiographs obtained from the files of totally edentulous patients were used. Digitization was done by means of a scanner with brightness and contrast adjustment, as well as image inversion. The extension of mandibular canal was divided into anterior, middle, and posterior regions, and the presence of a radiopaque line that characterized the mandibular canal was classified according to a 5-point confidence scale. The mental foramen was classified in 4 types: continuous, separated, diffuse, and unidentified. Both conventional and inverted scanned panoramic radiographs were evaluated by 3 calibrated implantologists at 2 distinct moments with a minimum interval of 10 days between them. Intraexaminer agreement was evaluated by Kappa statistics by point and by 95% confidence interval. Because the intraexaminer level of agreement was low, interexaminer agreements could not be carried out. The results showed a substantial (in 2 situations), moderate (in 16 situations), and fair (in 18 situations) intraexaminer agreement for mandibular canal and a substantial (in 1 situation), fair (in 1 situation), and moderate (in 10 situations) intraeaminer agreement for mental foramen. There were no statistically significant differences in most instances. In conclusion, the diagnostic agreement of conventional and inverted scanned panoramic radiographs for detection of mandibular canal and mental foramen was low. PMID:15008448

  8. Agreement between the Perceived and Actual Fruit and Vegetable Nutrition Environments among Low-Income Urban Women.

    PubMed

    Stallings, Tiffany L; Gazmararian, Julie A; Goodman, Michael; Kleinbaum, David

    2015-11-01

    The food environment is described by two measures: store-level (actual) and individual-level (perceived). Understanding the relationship between actual and perceived fruit and vegetable (F&V) nutrition environments is important as their association may influence F&V purchases and consumption. The study objective was to assess agreement between perceived and actual environment measures of availability, quality, and affordability/price for fresh and canned/frozen F&V. African American WIC recipients (n=84) self-reported perceptions corresponding to chain food stores (n=13) which were then assessed by surveyors. Nearly 80% of participants had positive perceptions of stores' F&V availability, quality, and affordability. Store assessments indicated high F&V availability and quality and lowest prices for canned varieties. Kappa statistics, sensitivity, and specificity calculated agreement between perceived and actual measures. Results indicated slight to fair agreements. Agreements were highest for quality measures (kappa=0.25 (95% CI:0.08-0.42), p=.008). Research implications include promoting nutrition education and resident interviewing to understand F&V expectations.

  9. Agreement between the Perceived and Actual Fruit and Vegetable Nutrition Environments among Low-Income Urban Women.

    PubMed

    Stallings, Tiffany L; Gazmararian, Julie A; Goodman, Michael; Kleinbaum, David

    2015-11-01

    The food environment is described by two measures: store-level (actual) and individual-level (perceived). Understanding the relationship between actual and perceived fruit and vegetable (F&V) nutrition environments is important as their association may influence F&V purchases and consumption. The study objective was to assess agreement between perceived and actual environment measures of availability, quality, and affordability/price for fresh and canned/frozen F&V. African American WIC recipients (n=84) self-reported perceptions corresponding to chain food stores (n=13) which were then assessed by surveyors. Nearly 80% of participants had positive perceptions of stores' F&V availability, quality, and affordability. Store assessments indicated high F&V availability and quality and lowest prices for canned varieties. Kappa statistics, sensitivity, and specificity calculated agreement between perceived and actual measures. Results indicated slight to fair agreements. Agreements were highest for quality measures (kappa=0.25 (95% CI:0.08-0.42), p=.008). Research implications include promoting nutrition education and resident interviewing to understand F&V expectations. PMID:26548680

  10. Zonal Two Equation Kappa-Omega Turbulence Models for Aerodynamic Flows

    NASA Technical Reports Server (NTRS)

    Menter, Florian R.

    1993-01-01

    Two new versions of the kappa-omega two-equation turbulence model will be presented. The new Baseline (BSL) model is designed to give results similar to those of the original kappa-omega model of Wilcox, but without its strong dependency on arbitrary freestream values. The BSL model is identical to the Wilcox model in the inner 50% of the boundary-layer but changes gradually to the standard kappa-epsilon model (in a kappa- omega formulation) towards the boundary-layer edge. The free shear layers. The second version of the model is called Shear-Stress Transport (SST) model. It is a variation of the BSL model with the additional ability to account for the transport of the principal turbulent shear stress in adverse pressure gradient boundary-layers. The model is based on Bradshaw's assumption that the principal shear-stress is proportional to the turbulent kinetic energy, which is introduced into the definition of the eddy-viscosity. Both models are tested for a large number of different flowfields. The results of the BSL model are similar to those of the original kappa-omega model, but without the undesirable freestream dependency. The predictions of the SST model are also independent of the freestream values but show better agreement with experimental data for adverse pressure gradient boundary-layer flows.

  11. Characterizing cometary electrons with kappa distributions

    NASA Astrophysics Data System (ADS)

    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.; Goldstein, J.; Goldstein, R.; Henri, P.; Madanian, H.; Mandt, K.; Mokashi, P.; Pollock, C.; Rahmati, A.; Samara, M.; Schwartz, S. J.

    2016-08-01

    The Rosetta spacecraft has escorted comet 67P/Churyumov-Gerasimenko since 6 August 2014 and has offered an unprecedented opportunity to study plasma physics in the coma. We have used this opportunity to make the first characterization of cometary electrons with kappa distributions. Two three-dimensional kappa functions were fit to the observations, which we interpret as two populations of dense and warm (density = 10 cm-3, temperature = 2 × 105 K, invariant kappa index = 10->1000), and rarefied and hot (density = 0.005 cm-3, temperature = 5 × 105 K, invariant kappa index = 1-10) electrons. We fit the observations on 30 October 2014 when Rosetta was 20 km from 67P, and 3 AU from the Sun. We repeated the analysis on 15 August 2015 when Rosetta was 300 km from the comet and 1.3 AU from the Sun. Comparing the measurements on both days gives the first comparison of the cometary electron environment between a nearly inactive comet far from the Sun and an active comet near perihelion. We find that the warm population density increased by a factor of 3, while the temperature cooled by a factor of 2, and the invariant kappa index was unaffected. We find that the hot population density increased by a factor of 10, while the temperature and invariant kappa index were unchanged. We conclude that the hot population is likely the solar wind halo electrons in the coma. The warm population is likely of cometary origin, but its mechanism for production is not known.

  12. One-dimensional particle-in-cell simulations of electrostatic Bernstein waves in plasmas with kappa velocity distributions

    NASA Astrophysics Data System (ADS)

    Abdul, R. F.; Mace, R. L.

    2015-10-01

    Electrostatic Bernstein waves that propagate exactly perpendicularly to a static magnetic field in an electron-ion plasma are investigated using one-and-two-halves dimensional particle-in-cell simulations. An ion-to-electron mass ratio of mi/me = 100 is used, allowing sufficient separation of the electron and ion time scales while still accounting for the ion dynamics without resorting to exceptionally long simulation run times. As a consequence of the mass ratio used, both the high frequency electron Bernstein wave and the lower frequency ion Bernstein wave are resolved within a single simulation run. The simulations presented here use isotropic three-dimensional kappa velocity distributions as well as the widely used Maxwellian velocity distribution, and the results from using each of these velocity distributions are analysed and compared. The behaviour of the Bernstein waves is found to be significantly dependent on the spectral index, κ, of the kappa distribution in all frequency domains of the Bernstein waves. In both the Maxwellian and kappa cases, spectral analysis of the electric field (wave) intensities, as a function of ω and k, show very good agreement between the simulation results and the linear dispersion relation for Bernstein waves. This agreement serves to validate the simulation techniques used, as well as the theory of Bernstein waves in plasmas with a kappa velocity distribution. The intensity of the field fluctuations in the simulations containing an abundance of superthermal particles, i.e., where the plasma has a kappa velocity distribution with a low kappa index, is slightly higher compared to the simulations of plasmas with higher kappa values. The plasmas with low kappa values also exhibit a broader region in frequency space of high intensity field fluctuations.

  13. One-dimensional particle-in-cell simulations of electrostatic Bernstein waves in plasmas with kappa velocity distributions

    SciTech Connect

    Abdul, R. F. Mace, R. L.

    2015-10-15

    Electrostatic Bernstein waves that propagate exactly perpendicularly to a static magnetic field in an electron-ion plasma are investigated using one-and-two-halves dimensional particle-in-cell simulations. An ion-to-electron mass ratio of m{sub i}/m{sub e} = 100 is used, allowing sufficient separation of the electron and ion time scales while still accounting for the ion dynamics without resorting to exceptionally long simulation run times. As a consequence of the mass ratio used, both the high frequency electron Bernstein wave and the lower frequency ion Bernstein wave are resolved within a single simulation run. The simulations presented here use isotropic three-dimensional kappa velocity distributions as well as the widely used Maxwellian velocity distribution, and the results from using each of these velocity distributions are analysed and compared. The behaviour of the Bernstein waves is found to be significantly dependent on the spectral index, κ, of the kappa distribution in all frequency domains of the Bernstein waves. In both the Maxwellian and kappa cases, spectral analysis of the electric field (wave) intensities, as a function of ω and k, show very good agreement between the simulation results and the linear dispersion relation for Bernstein waves. This agreement serves to validate the simulation techniques used, as well as the theory of Bernstein waves in plasmas with a kappa velocity distribution. The intensity of the field fluctuations in the simulations containing an abundance of superthermal particles, i.e., where the plasma has a kappa velocity distribution with a low kappa index, is slightly higher compared to the simulations of plasmas with higher kappa values. The plasmas with low kappa values also exhibit a broader region in frequency space of high intensity field fluctuations.

  14. Phi Delta Kappa at the Threshold

    ERIC Educational Resources Information Center

    Walling, Donovan R.

    2006-01-01

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

  15. Kappa opioid receptors on dopaminergic neurons are necessary for kappa-mediated place aversion.

    PubMed

    Chefer, Vladimir I; Bäckman, Cristina M; Gigante, Eduardo D; Shippenberg, Toni S

    2013-12-01

    Kappa-opioid receptor (KOR) agonists have dysphoric properties in humans and are aversive in rodents. This has been attributed to the activation of KORs within the mesolimbic dopamine (DA) system. However, the role of DA in KOR-mediated aversion and stress remains divisive as recent studies have suggested that activation of KORs on serotonergic neurons may be sufficient to mediate aversive behaviors. To address this question, we used conditional knock-out (KO) mice with KORs deleted on DA neurons (DAT(Cre/wt)/KOR(loxp/loxp), or DATCre-KOR KO). In agreement with previous findings, control mice (DAT(Cre/wt)/KOR(wt/wt) or WT) showed conditioned place aversion (CPA) to the systemically administered KOR agonist U69,593. In contrast, DATCre-KOR KO mice did not exhibit CPA with this same agonist. In addition, in vivo microdialysis showed that systemic U69,593 decreased overflow of DA in the nucleus accumbens (NAc) in WT mice, but had no effect in DATCre-KOR KO mice. Intra- ventral tegmental area (VTA) delivery of KORs using an adeno-associated viral gene construct, resulted in phenotypic rescue of the KOR-mediated NAc DA response and aversive behavior in DATCre-KOR KO animals. These results provide evidence that KORs on VTA DA neurons are necessary to mediate KOR-mediated aversive behavior. Therefore, our data, along with recent findings, suggest that the neuronal mechanisms of KOR-mediated aversive behavior may include both dopaminergic and serotonergic components. PMID:23921954

  16. Interobserver Agreement in the Classification of Partial-Thickness Rotator Cuff Tears Using the Snyder Classification System

    PubMed Central

    Lee, Christopher S.; Davis, Shane M.; Doremus, Brittany; Kouk, Shalen; Stetson, William B.

    2016-01-01

    Background: At present, there is no widely accepted classification system for partial-thickness rotator cuff tears, and as a result, optimal treatment remains controversial. Purpose: To examine the interobserver reliability and accuracy of classifying partial rotator cuff tears using the Snyder classification system. We hypothesized that the Snyder classification would be reproducible with high reliability and accuracy. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: Twenty-seven orthopaedic surgeons reviewed 10 video-recorded shoulder arthroscopies. Each surgeon was provided with a description of the Snyder classification system for partial-thickness rotator cuff tears and was then instructed to use this system to describe each tear. Interrater kappa statistics and percentage agreement between observers were calculated to measure the level of agreement. Surgeon experience as well as fellowship training was evaluated to determine possible correlations. Results: A kappa coefficient of 0.512 indicated moderate reliability between surgeons using the Snyder classification to describe partial-thickness rotator cuff tears. The mean correct score was 80%, which indicated “very good” agreement. There was no correlation between the number of shoulder arthroscopies performed per year and fellowship training and the number of correct scores. Conclusion: The Snyder classification system is reproducible and can be used in future research studies in analyzing the treatment options of partial rotator cuff tears. PMID:27738643

  17. 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.

  18. Measuring agreement between decision support reminders: the cloud vs. the local expert

    PubMed Central

    2014-01-01

    Background A cloud-based clinical decision support system (CDSS) was implemented to remotely provide evidence-based guideline reminders in support of preventative health. Following implementation, we measured the agreement between preventive care reminders generated by an existing, local CDSS and the new, cloud-based CDSS operating on the same patient visit data. Methods Electronic health record data for the same set of patients seen in primary care were sent to both the cloud-based web service and local CDSS. The clinical reminders returned by both services were captured for analysis. Cohen’s Kappa coefficient was calculated to compare the two sets of reminders. Kappa statistics were further adjusted for prevalence and bias due to the potential effects of bias in the CDS logic and prevalence in the relative small sample of patients. Results The cloud-based CDSS generated 965 clinical reminders for 405 patient visits over 3 months. The local CDSS returned 889 reminders for the same patient visit data. When adjusted for prevalence and bias, observed agreement varied by reminder from 0.33 (95% CI 0.24 – 0.42) to 0.99 (95% CI 0.97 – 1.00) and demonstrated almost perfect agreement for 7 of the 11 reminders. Conclusions Preventive care reminders delivered by two disparate CDS systems show substantial agreement. Subtle differences in rule logic and terminology mapping appear to account for much of the discordance. Cloud-based CDSS therefore show promise, opening the door for future development and implementation in support of health care providers with limited resources for knowledge management of complex logic and rules. PMID:24720863

  19. The Effect of Asymmetry on the 2x2 Kappa Coefficient: Application to the Study of Learning Disabilities

    ERIC Educational Resources Information Center

    Rivas-Moya, Teresa; Gonzalez-Valenzuela, Maria-Jose

    2007-01-01

    In educational practice, for the evaluation and diagnosis of learning disabilities (LD), it is advisable to use standardized tests together with observation questionnaires. When observation questionnaires are used in the study of LD, Cohen's (1960) kappa coefficient (k) is frequently applied as a measure of agreement between two raters when they…

  20. Angle Kappa and its importance in refractive surgery

    PubMed Central

    Moshirfar, Majid; Hoggan, Ryan N.; Muthappan, Valliammai

    2013-01-01

    Angle kappa is the difference between the pupillary and visual axis. This measurement is of paramount consideration in refractive surgery, as proper centration is required for optimal results. Angle kappa may contribute to MFIOL decentration and its resultant photic phenomena. Adjusting placement of MFIOLs for angle kappa is not supported by the literature but is likely to help reduce glare and haloes. Centering LASIK in angle kappa patients over the corneal light reflex is safe, efficacious, and recommended. Centering in-between the corneal reflex and the entrance pupil is also safe and efficacious. The literature regarding PRK in patients with an angle kappa is sparse but centering on the corneal reflex is assumed to be similar to centering LASIK on the corneal reflex. Thus, centration of MFIOLs, LASIK, and PRK should be focused on the corneal reflex for patients with a large angle kappa. More research is needed to guide surgeons’ approach to angle kappa. PMID:24379548

  1. The reliability of lumbar motion palpation using continuous analysis and confidence ratings: choosing a relevant index of agreement

    PubMed Central

    Cooperstein, Robert; Young, Morgan

    2016-01-01

    Introduction: Most studies show motion palpation unreliable. This study’s primary objective was assessing its reliability using a continuous measure methods, most-fixated level paradigm, stratified by examiners’ confidence; and the secondary objective was comparing various indices of examiner agreement. Methods: Thirty-four minimally symptomatic participants were palpated in side posture by two experienced examiners. Interexaminer differences in identifying the most-fixated level and degree of examiner confidence were recorded. Indices of agreement were: Intraclass correlation coefficient, Mean and Median Examiner Absolute Examiner Differences, Root-Mean-Square Error and Bland-Altman Limits of Agreement. Results: Three of four reliability indices (excluding intraclass correlation) suggested on average examiners agreed on the most fixated motion segment, and agreement increased with confidence. Statistical measures of data dispersion were low. The analyses of subgroups were “fragile” due to small sample size. Discussion: Although subject homogeneity lowered ICC levels, the other reliability measures were not similarly impacted. Continuous measures statistical analysis demonstrates examiner agreement in situations where discrete analysis with kappa may not. Conclusion: Continuous analysis for the lumbar most-fixated level is reliable. Future studies will need a larger sample size to properly analyze subgroups based on examiner confidence. PMID:27385834

  2. Foundations of Statistical Mechanics in Space Plasmas

    NASA Astrophysics Data System (ADS)

    Livadiotis, G.

    2014-12-01

    Systems at thermal equilibrium have their distribution function of particle velocities stabilized into a Maxwell distribution, which is connected with the classical framework of Boltzmann-Gibbs (BG) statistical mechanics. However, Maxwell distributions are rare in space plasmas; the vast majority of these plasmas reside at stationary states out of thermal equilibrium, which are described by kappa distributions. Kappa distributions do not embody BG statistics, but instead, they are connected with the generalized statistical framework of non-extensive statistical mechanics that offers a solid theoretical basis for describing particle systems like collisionless space plasmas. Through the statistical formulation of kappa distributions, basic thermodynamic variables like the temperature, thermal pressure, and entropy, become physically meaningful and determinable, similarly to their classical BG description at thermal equilibrium. In addition, useful formulations of kappa distributions were developed in order to describe multi-particle distributions, and particle systems with a non-zero potential energy. Finally, the variety of kappa distribution formulations and the proven tools of non-extensive statistical mechanics have been successfully applied to a numerous space plasmas throughout the heliosphere, from the inner heliosphere (e.g., the solar wind and planetary magnetospheres) to the outer heliosphere (e.g., the inner heliosheath) and beyond.

  3. CNK1 promotes invasion of cancer cells through NF-kappaB-dependent signaling.

    PubMed

    Fritz, Rafael D; Radziwill, Gerald

    2010-03-01

    Hallmarks of cancer cells are uncontrolled proliferation, evasion of apoptosis, angiogenesis, cell invasion, and metastasis, which are driven by oncogenic activation of signaling pathways. Herein, we identify the scaffold protein CNK1 as a mediator of oncogenic signaling that promotes invasion in human breast cancer and cervical cancer cells. Downregulation of CNK1 diminishes the invasiveness of cancer cells and correlates with reduced expression of matrix metalloproteinase 9 (MMP-9) and membrane-type 1 MMP (MT1-MMP). Ectopic expression of CNK1 elevates MT1-MMP promoter activity in a NF-kappaB-dependent manner. Moreover, CNK1 cooperates with the NF-kappaB pathway, but not with the extracellular signal-regulated protein kinase pathway, to promote cell invasion. Mechanistically, CNK1 regulates the alternative branch of the NF-kappaB pathway because knockdown of CNK1 interferes with processing of NF-kappaB2 p100 to p52 and its localization to the nucleus. In agreement with this, the invasion of CNK1-depleted cells is less sensitive to RelB downregulation compared with the invasion of control cells. Moreover, CNK1-dependent MT1-MMP promoter activation is blocked by RelB siRNA. Thus, CNK1 is an essential mediator of an oncogenic pathway involved in invasion of breast and cervical cancer cells and is therefore a putative target for cancer therapy.

  4. Impact of educational intervention on the inter-rater agreement of nasal endoscopy interpretation

    PubMed Central

    Colley, Patrick; Mace, Jess C.; Schaberg, Madeleine R.; Smith, Timothy L.; Tabaee, Abtin

    2015-01-01

    OBJECTIVE Nasal endoscopy is integral to the evaluation of sinonasal disorders. However, prior studies have shown significant variability in the inter-rater agreement of nasal endoscopy interpretation amongst practicing rhinologists. The objective of the current study is to evaluate the inter-rater agreement of nasal endoscopy amongst otolaryngology residents from a single training program at baseline and following an educational intervention. METHODS 11 otolaryngology residents completed nasal endoscopy grading forms for 8 digitally recorded nasal endoscopic examinations. An instructional lecture reviewing nasal endoscopy interpretation was subsequently provided. The residents then completed grading forms for 8 different nasal endoscopic examinations. Inter-rate agreement amongst residents for the pre- and post-lecture videos was calculated using the unweighted Fleiss’ kappa statistic (Kf) and intra-class correlation agreement (ICC). RESULTS Inter-rater agreement improved from a baseline level of fair (Kf range 0.268–0.383) to a post-educational level of moderate (Kf range 0.401–0.547) for nasal endoscopy findings of middle meatus mucosa, middle turbinate mucosa, middle meatus discharge, sphenoethmoid recess mucosa, sphenoethmoid recess discharge and atypical lesions (ICC, p<0.001). The baseline level of agreement for evaluation of nasal septum deviation was poor/fair and did not improve following educational intervention. CONCLUSIONS This study demonstrates a limited baseline level of inter-rater agreement of nasal endoscopy interpretation amongst otolaryngology residents. The inter-rater agreement for the majority of the characteristics that were evaluated improved after educational intervention. Further study is needed to improve nasal endoscopy interpretation. PMID:25781864

  5. Evaluation of Agreement between HRT III and iVue OCT in Glaucoma and Ocular Hypertension Patients.

    PubMed

    Perdicchi, A; Iester, M; Iacovello, D; Cutini, A; Balestrieri, M; Mutolo, M G; Ferreras, A; Contestabile, M T; Recupero, S M

    2015-01-01

    Purpose. To determine the agreement between Moorfields Regression Analysis (MRA), Glaucoma Probability Score (GPS) of Heidelberg retinal tomograph (HRT III), and peripapillary nerve fibers thickness by iVue Optical Coherence Tomography (OCT). Methods. 72 eyes with ocular hypertension or primary open angle glaucoma (POAG) were included in the study: 54 eyes had normal visual fields (VF) and 18 had VF damage. All subjects performed achromatic 30° VF by Octopus Program G1X dynamic strategy and were imaged with HRT III and iVue OCT. Sectorial and global MRA, GPS, and OCT parameters were used for the analysis. Kappa statistic was used to assess the agreement between methods. Results. A significant agreement between iVue OCT and GPS for the inferotemporal quadrant (κ: 0.555) was found in patients with abnormal VF. A good overall agreement between GPS and MRA was found in all the eyes tested (κ: 0.511). A good agreement between iVue OCT and MRA was shown in the superonasal (κ: 0.656) and nasal (κ: 0.627) quadrants followed by the superotemporal (κ: 0.602) and inferotemporal (κ: 0.586) sectors in all the studied eyes. Conclusion. The highest percentages of agreement were found per quadrant of the MRA and the iVue OCT confirming that in glaucoma damage starts from the temporal hemiretina. PMID:26788363

  6. Rupture Paths in Kappa-Maps: Quantitative Insights on Heterogeneous Earthquake Ruptures From Energy Arguments.

    NASA Astrophysics Data System (ADS)

    Ampuero, J.; Ripperger, J.; Mai, M.

    2005-12-01

    Earthquake rupture is a notoriously complex process, at all observable scales. Although heterogeneities of strength and initial stress contribute to this rupture complexity, a systematic approach to quantify their effect has not yet been attempted. For instance, little is known about the relation between the final size of an earthquake and the statistical properties of initial strength excess fields. Canonical cases of dynamic rupture (e.g. uniform initial stress and friction properties), can be characterized by two non-dimensional numbers: the S-parameter (ratio of strength excess to stress drop) and the Kappa-parameter (ratio of static energy release rate to fracture energy, Madariaga and Olsen, 2000). The latter was introduced as a global parameter, involving the fault depth or asperity size as the fundamental scale. However, because faults contain heterogeneities at all scales it is not clear how a single scale-length may be relevant to define Kappa. We define here a scale-dependent Kappa-map, based on classical energy concepts in fracture mechanics. In 2D these maps can be defined exactly, and their efficient computation is implemented as a series of FFT-convolutions, by scaled analytical filters related to stress intensity factor weight functions. For given heterogeneous stress drop and fracture energy, such Kappa-maps are useful to predict nucleation properties and final moment, as we illustrate through increasingly complex examples complemented by dynamic rupture simulations. Other properties that can be derived from the 2D Kappa-maps, with additional assumptions, include radiated energy and rupture directivity. In 3D, the shape of the rupture front is unknown a priori and the energy release rate G might be non-uniform along the front. We therefore propose an approximate definition of Kappa in which G is estimated on circular patches. Comparisons with 3D dynamic rupture simulations on highly heterogeneous initial stress fields show that the final moment can

  7. Evaluation of an Advanced-Practice Physical Therapist in a Specialty Shoulder Clinic: Diagnostic Agreement and Effect on Wait Times

    PubMed Central

    Robarts, Susan; Kennedy, Deborah; McKnight, Cheryl; MacLeod, Anne Marie; Holtby, Richard

    2013-01-01

    ABSTRACT Purpose: To examine the role of an advanced-practice physiotherapist (APP) with respect to (1) agreement with an orthopaedic surgeon on diagnosis and management of patients with shoulder problems; (2) wait times; and (3) satisfaction with care. Methods: This prospective study involved patients with shoulder complaints who were referred to a shoulder specialist in a tertiary care centre. Agreement was examined on seven major diagnostic categories, need for further examination and surgery, and type of surgical procedure. Wait times were compared between the APP- and surgeon-led clinics from referral date to date of initial consultation, date of final diagnostic test, and date of confirmed diagnosis and planned treatment. A modified and validated version of the Visit-Specific Satisfaction Instrument assessed satisfaction in seven domains. Kappa (κ) coefficients and bias- and prevalence-adjusted kappa (PABAK) values were calculated, and strength of agreement was categorized. Wait time and satisfaction data were examined using non-parametric statistics. Results: Agreement on major diagnostic categories varied from 0.68 (good) to 0.96 (excellent). Agreement with respect to indication for surgery was κ=0.75, p<0.001; 95% CI, 0.62–0.88 (good). Wait time for APP assessment was significantly shorter than wait time for surgeon consultation at all time points (p<0.001); the surgeon's wait time was significantly reduced over 3 years. High satisfaction was reported in all components of care received from both health care providers. Conclusions: Using experienced physiotherapists in an extended role reduces wait times without compromising patient clinical management and overall satisfaction. PMID:24381382

  8. Comparison of validity of assessment methods using indices of adjusted agreement.

    PubMed

    Nam, Jun-mo

    2007-02-10

    For comparing the validity of rating methods, the adjusted kappa (S coefficient) and Yule's Y index are better than Cohen's kappa which is affected by marginal probabilities. We consider a validity study in which a subject is assessed as exposed or not-exposed by two competing rating methods and the gold standard. We are interested in one of the methods, which is closer in agreement with the gold standard. We present statistical methods taking correlations into account for comparing the validity of the rating methods using S coefficient and Y index. We show how the S coefficient and Yule's Y index are related to sensitivity and specificity. In comparing the two rating methods, the preference is clear when the inference is the same for both S and Y. If the inference using S differs from that using Y, then it is not obvious how to decide a preference. This may occur when one rating method is better than the other in sensitivity but not in specificity. Numerical examples for comparing asbestos-exposure assessment methods are illustrated.

  9. Plasma Dispersion Function for the Kappa Distribution

    NASA Technical Reports Server (NTRS)

    Podesta, John J.

    2004-01-01

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

  10. Nonlinear plasma processes and the formation of electron kappa distribution

    NASA Astrophysics Data System (ADS)

    Yoon, Peter

    2016-07-01

    The goal of nonequilibrium statistical mechanics is to establish fundamental relationship between the time irreversible macroscopic dynamics and the underlying time reversible behavior of microscopic system. The paradigm of achieving this seemingly paradoxical goal is through the concept of probability. For classical systems Boltzmann accomplished this through his H theorem and his kinetic equation for dilute gas. Boltzmann's H function is the same as classical extensive entropy aside from the minus sign, and his kinetic equation is applicable for short-range molecular interaction. For plasmas, the long-range electromagnetic force dictates the inter-particular interaction, and the underlying entropy is expected to exhibit non-extensive, or non-additive behavior. Among potential models for the non-additive entropy, the celebrated Tsallis entropy is the most well known. One of the most useful fundamental kinetic equations that governs the long-range plasma interaction is that of weak turbulence kinetic theory. At present, however, there is no clear-cut connection between the Tsallis entropy and the kinetic equations that govern plasma behavior. This can be contrasted to Boltzmann's H theorem, which is built upon his kinetic equation. The best one can do is to show that the consequences of Tsallis entropy and plasma kinetic equation are the same, that is, they both imply kappa distribution. This presentation will overview the physics of electron acceleration by beam-generated Langmuir turbulence, and discuss the asymptotic solution that rigorously can be shown to correspond to the kappa distribution. Such a finding is a strong evidence, if not water-tight proof, that there must be profound inter-relatioship between the Tsallis thermostatistical theory and the plasma kinetic theory.

  11. Expression of immunoglobulin kappa and lambda chains in mink.

    PubMed

    Bovkun, L A; Peremislov, V V; Nayakshin, A M; Belousov, E S; Mechetina, L V; Aasted, B; Taranin, A V

    1993-08-01

    The ratio of kappa and lambda chains of immunoglobulins varies significantly from one species to another. It has previously been thought that lambda was only type expressed in mink. We tested mink immunoglobulin light chains using two monoclonal antibodies G80 and G88. It has been shown that G80 and G88 specifically recognize two antigenically different subpopulations of the light chains. Immunochemical analysis of these subpopulations separated by affinity chromatography suggested that they represent lambda and kappa types of light chains, respectively. Screening of a mink cDNA library with monoclonal antibody G88 resulted in the isolation of clone pIGK-1 containing kappa chain-encoding sequence. The cDNA insert of pIGK-1 included most of the V segment, as well as the J, C and 3' untranslated sequences. Mink V kappa sequence shown the highest homology with the human V kappa II subgroup genes (76-79%). Mink C kappa sequence was 53-63% homologous to C kappa of other species. The striking feature of mink C kappa chain is the presence of glutamine in the C-terminal position. Southern blot analysis suggested that mink haploid genome has one C kappa gene and multiple V kappa genes. The kappa:lambda chain ratio in the 12 minks studied was, on the average, 46:54. The same ratio was observed for the kappa- and lambda-producing cells in the mesenteric lymph nodes. The five previously identified mink light chain allotypes were assigned to the lambda chains, thereby confirming that lambda chains in this species are additionally subdivided into several subtypes.

  12. Inhibitors of NF-kappaB signaling: 785 and counting.

    PubMed

    Gilmore, T D; Herscovitch, M

    2006-10-30

    Nuclear factor kappa B (NF-kappaB) transcription factors regulate several important physiological processes, including inflammation and immune responses, cell growth, apoptosis, and the expression of certain viral genes. Therefore, the NF-kappaB signaling pathway has also provided a focus for pharmacological intervention, primarily in situations of chronic inflammation or in cancer, where the pathway is often constitutively active and plays a key role in the disease. Now that many of the molecular details of the NF-kappaB pathway are known, it is clear that modulators of this pathway can act at several levels. As described herein, over 750 inhibitors of the NF-kappaB pathway have been identified, including a variety of natural and synthetic molecules. These compounds include antioxidants, peptides, small RNA/DNA, microbial and viral proteins, small molecules, and engineered dominant-negative or constitutively active polypeptides. Several of these molecules act as general inhibitors of NF-kappaB induction, whereas others inhibit specific pathways of induction. In addition, some compounds appear to target multiple steps in the NF-kappaB pathway. Compounds designed as specific NF-kappaB inhibitors are not yet in clinical use, but they are likely to be developed as treatments for certain cancers and neurodegenerative and inflammatory diseases. Moreover, the therapeutic and preventative effects of many natural products may, at least in part, be due to their ability to inhibit NF-kappaB. PMID:17072334

  13. Spectral geometry of {kappa}-Minkowski space

    SciTech Connect

    D'Andrea, Francesco

    2006-06-15

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

  14. NF-kappaB activation contributes to anthracycline resistance pathway in human ovarian carcinoma cell line A2780.

    PubMed

    Salvatore, Carmela; Camarda, Grazia; Maggi, Carlo Alberto; Goso, Cristina; Manzini, Stefano; Binaschi, Monica

    2005-09-01

    The development of chemoresistance is a major obstacle for successful anticancer therapy. Understanding the molecular mechanisms leading to chemoresistance is a rational step to improve the therapeutic efficacy of cytotoxic drugs. Since anthracyclines play an important role in cancer chemotherapy, we have generated a human ovarian tumor cell line resistant to sabarubicin (MEN 10755), the newest anthracycline molecule in clinical development. Expression of the transporter protein MRP that affected sabarubicin uptake, and a reduced DNA topoisomerase II content in A2780/saba cells was observed. Since the poisoning of DNA topoisomerase II results in DNA damage, which is a critical signal for NF-kappaB activation, we explored if this transcription factor has a role in the chemoresistance to anthracyclines. We showed a reduced NF-kappaB activation in the resistant cell line. Moreover, qualitative changes in NF-kappaB dimer formation between the two cell lines were observed. In agreement with the hypothesis of a role of NF-kappaB in mediating drug resistance, we showed that the pharmacological inhibition of NF-kappaB activation attenuated drug resistance in A2780/saba cells whereas it had no effect in A2780 cells. Altogether, these findings show that anthracycline resistance in A2780 cell lines is due to the coexpression of several molecular mechanisms.

  15. Inter-rater agreement for a retrospective exposure assessment of asbestos, chromium, nickel and welding fumes in a study of lung cancer and ionizing radiation.

    PubMed

    Seel, E A; Zaebst, D D; Hein, M J; Liu, J; Nowlin, S J; Chen, P

    2007-10-01

    A retrospective exposure assessment of asbestos, welding fumes, chromium and nickel (in welding fumes) was conducted at the Portsmouth Naval Shipyard for a nested case-control study of lung cancer risk from external ionizing radiation. These four contaminants were included because of their potential to confound or modify the effect of a lung cancer-radiation relationship. The exposure assessment included three experienced industrial hygienists from the shipyard who independently assessed exposures for 3519 shop/job/time period combinations. A consensus process was used to resolve estimates with large differences. Final exposure estimates were linked to employment histories of the 4388 study subjects to calculate their cumulative exposures. Inter-rater agreement analyses were performed on the original estimates to better understand the estimation process. Although concordance was good to excellent (78-99%) for intensity estimates and excellent (96-99%) for frequency estimates, overall simple kappa statistics indicated only slight agreement beyond chance (kappa < 0.2). Unbalanced distributions of exposure estimates partly contributed to the weak observed overall inter-rater agreement. Pairwise weighted kappa statistics revealed better agreement between two of the three panelists (kappa = 0.19-0.65). The final consensus estimates were similar to the estimates made by these same two panelists. Overall welding fume exposures were fairly stable across time at the shipyard while asbestos exposures were higher in the early years and fell in the mid-1970s. Mean cumulative exposure for all study subjects was 520 fiber-days cc(-1) for asbestos and 1000 mg-days m(-3) for welding fumes. Mean exposure was much lower for nickel (140 microg-days m(-3)) and chromium (45 microg-days m(-3)). Asbestos and welding fume exposure estimates were positively associated with lung cancer in the nested case-control study. The radiation-lung cancer relationship was attenuated by the inclusion

  16. Agreement of reported vascular access on the medical evidence report and on medicare claims at hemodialysis initiation

    PubMed Central

    2014-01-01

    Background The choice of vascular access type is an important aspect of care for incident hemodialysis patients. However, data from the Centers for Medicare & Medicaid Services (CMS) Medical Evidence Report (form CMS-2728) identifying the first access for incident patients have not previously been validated. Medicare began requiring that vascular access type be reported on claims in July 2010. We aimed to determine the agreement between the reported vascular access at initiation from form CMS-2728 and from Medicare claims. Methods This retrospective study used a cohort of 9777 patients who initiated dialysis in the latter half of 2010 and were eligible for Medicare at the start of renal replacement therapy to compare the vascular access type reported on form CMS-2728 with the type reported on Medicare outpatient dialysis claims for the same patients. For each patient, the reported access from each data source was compiled; the percent agreement represented the percent of patients for whom the access was the same. Multivariate logistic analysis was performed to identify characteristics associated with the agreement of reported access. Results The two data sources agreed for 94% of patients, with a Kappa statistic of 0.83, indicating an excellent level of agreement. Further, we found no evidence to suggest that agreement was associated with the patient characteristics of age, sex, race, or primary cause of renal failure. Conclusion These results suggest that vascular access data as reported on form CMS-2728 are valid and reliable for use in research studies. PMID:24507475

  17. Diagnostic agreement between a primary care physician and a teledermatologist for common dermatological conditions in North India

    PubMed Central

    Patro, Binod Kumar; Tripathy, Jaya Prasad; De, Dipankar; Sinha, Smita; Singh, Amarjeet; Kanwar, Amrinder Jit

    2015-01-01

    Background: Primary care physicians (PCPs) encounter a large number of patients with dermatological diseases. However, delivering appropriate management is a challenge considering the inadequate dermatology training offered during the undergraduate medical curriculum. Teledermatology is the clinical evaluation of skin lesions by dermatologists and allows patients to be diagnosed and treated from a distant site. It is seen as a potential solution to the shortage of specialists and providing equitable service in remote areas. Aim: The study was aimed at estimating the diagnostic agreement of common dermatological conditions between a PCP and a teledermatologist. Materials and Methods: Consecutive patients with dermatological ailments who attended a primary health care clinic were recruited into the study, examined by the PCP and offered a diagnosis. The clinical images and patients’ history were collected and transferred to a dermatologist at a tertiary center who also made a diagnosis. Agreement between diagnosis made by the PCPs and the teledermatologist was measured using kappa (κ) statistics. Results: Overall agreement between the diagnoses made by a PCP and the dermatologist was found to be 56%. Poor κ agreement (<0.4) was seen in the diagnosis of psoriasis and eczema. Conclusion: Teledermatology can supplement specialist dermatology service in remote areas. There was poor agreement in the diagnosis of psoriasis, classifying various types of eczematous conditions and fungal infections. Scarce manpower in dermatology at the primary health care level compounded by the burden of skin ailments necessitates training of PCPs in common dermatological conditions. PMID:25657912

  18. Deborah Partridge Wolfe: Biography of a Kappa Delta Pi Laureate

    ERIC Educational Resources Information Center

    van Hover, Stephanie

    2005-01-01

    In 1988, Kappa Delta Pi selected Dr. Deborah Partridge Wolfe for membership in its Laureate Chapter. Wolfe, a prominent African-American social educator, dedicated her career in education to living and promoting the key ideals of Kappa Delta Pi's mission: scholarship, excellence, diversity, inquiry, reflection, and fellowship. This biography of…

  19. Women in Leadership Roles in Phi Delta Kappa.

    ERIC Educational Resources Information Center

    Harder, Martha B.; And Others

    The professional and personal characteristics of the men and women in Phi Delta Kappa who hold the top elected positions in local chapters were compared, and the perceptions of these leaders of the impact of allowing women to be members of Phi Delta Kappa were assessed. A 43-item questionnaire was developed and mailed to 1,340 chapter presidents…

  20. The Earliest Black Members of Phi Beta Kappa.

    ERIC Educational Resources Information Center

    Titcomb, Caldwell

    2001-01-01

    Profiles several African American men who were black electees to the Phi Beta Kappa honorary society in the 19th century (no women were elected during this period), including George Washington Henderson, a former slave, who was the first African American elected. A sidebar describes the first African American woman elected to Phi Beta Kappa in…

  1. Kappa Opioid Receptor Agonist and Brain Ischemia

    PubMed Central

    Chunhua, Chen; Chunhua, Xi; Megumi, Sugita; Renyu, Liu

    2014-01-01

    Opioid receptors, especially Kappa opioid receptor (KOR) play an important role in the pathophysiological process of cerebral ischemia reperfusion injury. Previously accepted KOR agonists activity has included anti-nociception, cardiovascular, anti-pruritic, diuretic, and antitussive effects, while compelling evidence from various ischemic animal models indicate that KOR agonist have neuroprotective effects through various mechanisms. In this review, we aimed to demonstrate the property of KOR agonist and its role in global and focal cerebral ischemia. Based on current preclinical research, the KOR agonists may be useful as a neuroprotective agent. The recent discovery of salvinorin A, highly selective non-opioid KOR agonist, offers a new tool to study the role of KOR in brain HI injury and the protective effects of KOR agonist. The unique pharmacological profile of salvinorin A along with the long history of human usage provides its high candidacy as a potential alternative medication for brain HI injury. PMID:25574482

  2. Retroperitoneal Sarcoma Target Volume and Organ at Risk Contour Delineation Agreement Among NRG Sarcoma Radiation Oncologists

    SciTech Connect

    Baldini, Elizabeth H.; Abrams, Ross A.; Bosch, Walter; Roberge, David; Haas, Rick L.M.; Catton, Charles N.; Indelicato, Daniel J.; Olsen, Jeffrey R.; Deville, Curtiland; Chen, Yen-Lin; Finkelstein, Steven E.; DeLaney, Thomas F.; Wang, Dian

    2015-08-01

    Purpose: The purpose of this study was to evaluate the variability in target volume and organ at risk (OAR) contour delineation for retroperitoneal sarcoma (RPS) among 12 sarcoma radiation oncologists. Methods and Materials: Radiation planning computed tomography (CT) scans for 2 cases of RPS were distributed among 12 sarcoma radiation oncologists with instructions for contouring gross tumor volume (GTV), clinical target volume (CTV), high-risk CTV (HR CTV: area judged to be at high risk of resulting in positive margins after resection), and OARs: bowel bag, small bowel, colon, stomach, and duodenum. Analysis of contour agreement was performed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics. Results: Ten radiation oncologists contoured both RPS cases, 1 contoured only RPS1, and 1 contoured only RPS2 such that each case was contoured by 11 radiation oncologists. The first case (RPS 1) was a patient with a de-differentiated (DD) liposarcoma (LPS) with a predominant well-differentiated (WD) component, and the second case (RPS 2) was a patient with DD LPS made up almost entirely of a DD component. Contouring agreement for GTV and CTV contours was high. However, the agreement for HR CTVs was only moderate. For OARs, agreement for stomach, bowel bag, small bowel, and colon was high, but agreement for duodenum (distorted by tumor in one of these cases) was fair to moderate. Conclusions: For preoperative treatment of RPS, sarcoma radiation oncologists contoured GTV, CTV, and most OARs with a high level of agreement. HR CTV contours were more variable. Further clarification of this volume with the help of sarcoma surgical oncologists is necessary to reach consensus. More attention to delineation of the duodenum is also needed.

  3. Nuclear uptake control of NF-kappa B by MAD-3, an I kappa B protein present in the nucleus.

    PubMed Central

    Zabel, U; Henkel, T; Silva, M S; Baeuerle, P A

    1993-01-01

    I kappa B proteins specifically inhibit the DNA binding of NF-kappa B/Rel transcription factors. An additional role as inhibitors of nuclear uptake was supposed by subcellular fractionation and enucleation experiments. Using indirect immunofluorescence labeling of cells, we show here that the DNA-binding p50 and p65 subunits of NF-kappa B, as well as the I kappa B protein MAD-3, all occur in the nucleus when overexpressed on their own. Nuclear uptake of p65 and, to a lesser extent of p50, was, however, suppressed when MAD-3 was coexpressed. Likewise, nuclear uptake of MAD-3 was blocked by overexpressed p65 or p50. This directly demonstrates that I kappa B is a nuclear uptake regulatory protein and that the various subunits of NF-kappa B can mutually control their access to the nucleus. In the presence of MAD-3, antibodies specific for peptides overlapping the nuclear location signal (NLS) sequences of p65 and p50 could not recognize their epitopes on NF-kappa B, suggesting that the I kappa B protein rendered the signals inaccessible for NLS receptors. Images PMID:7679069

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

    SciTech Connect

    Wei Li; Kwang, Jimmy; Wang Jin; Shi Lei; Yang Bing; Li Yongqing; Liu Jue

    2008-08-15

    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 demonstrated 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.

  5. Method for nondestructive testing using multiple-energy CT and statistical pattern classification

    NASA Astrophysics Data System (ADS)

    Homem, Murillo R. P.; Mascarenhas, Nelson D. A.; Cruvinel, Paulo E.

    1999-10-01

    This paper reports on how multiple energy techniques in X and gamma-ray CT scanning are able to provide good results with the use of Statistical Pattern Classification theory. We obtained a set of four images with different energies (40, 60, 85 and 662 keV) containing aluminum, phosphorus, calcium, water and plexiglass, with a minitomograph scanner for soil science. We analyzed those images through both a supervised classifier based on the maximum-likelihood criterion under the multivariate Gaussian model and a supervised contextual classifier based on the ICM (iterated conditional modes) algorithm using an a priori Potts-Strauss model. A comparison between them was performed through the statistical kappa coefficient. A feature selection procedure using the Jeffries- Matusita (J-M) Distance was also performed. Both the classification and the feature selection procedures were found to be in agreement with the predicted discrimination given by the separation of the linear attenuation coefficient curves for different materials.

  6. Framingham Ten-Year General Cardiovascular Disease Risk: Agreement between BMI-Based and Cholesterol-Based Estimates in a South Asian Convenience Sample

    PubMed Central

    Jones, Charlotte A.; Ross, Leanne; Surani, Nadia; Dharamshi, Narissa; Karmali, Karima

    2015-01-01

    The goal of this analysis was to determine the agreement between body mass index-based and cholesterol-based ten-year Framingham general cardiovascular disease risk scores among a convenience sample of 773 South Asian Canadian adults attending community-based screening clinics. Scores were calculated using age, systolic blood pressure, antihypertensive use, current smoking, diabetes, and total cholesterol and high density lipoprotein (for cholesterol-based risk) or height and weight (for body mass index-based risk). Mean risk score differences (body mass index-based risk minus cholesterol-based risk) were estimated using paired t-tests. Bland-Altman plots were used to assess agreement between scores. Finally, agreement across risk categories (low [<10%], moderate [10% to <20%], high [> = 20%]) was examined using the kappa statistic. Average agreement between the two risk scores was quite good overall (mean differences of 0.6% for men and 0.5% for women), but increased to about 3% among participants 60–74 years of age. However, Bland-Altman plots revealed that the differences between the two scores and the variability of the differences increased with increasing average 10-year risk. In terms of clinical importance, the limits of agreement were reasonable for women < 60 years (95% confidence interval: -3.2% to 3.1%), but of concern for women 60-74 years (95% confidence interval: -6.0% to 12.3%), men < 60 years (95% confidence interval: -7.1% to 7.3%) and men 6-074 years (95% confidence interval: -13.8% to 18.8%). Agreement across categories was moderate for most sex and age groups examined (kappa values: 0.51 for women < 60 years, 0.50 for women 60-74 years, 0.65 for men < 60 years), except for men 60-74 years, where agreement was only fair (kappa = 0.26). In light of these disagreements, evaluation of a participant’s change in cardiovascular disease risk over time will necessitate use of the same risk score (i.e., either body mass index-based or cholesterol

  7. Syntheses and properties of {kappa}-phase organic superconductors

    SciTech Connect

    Wang, H.H.; Carlson, K.D.; Geiser, U.; Kini, A.M.; Schultz, A.J.; Williams, J.M.; Welp, U.; Darula, K.E.; Hitsman, V.M.; Lathrop, M.W.; Megna, L.A.; Mobley, P.R.; Yaconi, G.A.; Schirber, J.E.; Overmyer, D.L.

    1991-12-31

    The syntheses and physical properties of {kappa}-(ET){sub 2}Cu[N(CN){sub 2}]X (X=Br and Cl) are summarized. The {kappa}-(ET){sub 2}Cu[N(CN){sub 2}]Br salt is the highest {Tc} radical-cation based ambient pressure organic superconductor ({Tc}=11.6 K), and the {kappa}-(ET){sub 2}Cu[N(CN){sub 2}]Cl salt becomes a superconductor at even higher {Tc} under 0.3 kbar hydrostatic pressure ({Tc}=12.8 K). The similarities and differences between {kappa}-(ET){sub 2}Cu[N(CN){sub 2}]Br and {kappa}-(ET){sub 2}Cu(NCS){sub 2} ({Tc}=10.4 K) are presented. The X-ray structures at 127 K reveal that the the S{hor_ellipsis}S contacts shorten between ET dimers in the former compound while the S{hor_ellipsis}S contacts shorten within dimers in the latter. The difference in their ESR linewidth behavior is also explained in terms of the structural differences. A semiconducting compound, (ET)Cu[N(CN){sub 2}]{sub 2}, isolated during {kappa}-(ET){sub 2}Cu[N(CN){sub 2}]Cl synthesis is also reported. The ESR measurements of the {kappa}-(ET){sub 2}Cu[N(CN){sub 2}]Cl salt indicate that the phase transition near 40 K is similar to the spin density wave transition in (TMTSF){sub 2}SbF{sub 6}. A new class of organic superconductors, {kappa}-(ET){sub 2}Cu{sub 2}(CN){sub 3} and {kappa}-(ET){sub 2}Cu{sub 2}(CN){sub 3}-{delta}Br{delta}, is reported with {Tc}`s of 2.8 K (1.5 kbar) and 2.6 K (1 kbar), respectively.

  8. Activation of transcription factor IL-6 (NF-IL-6) and nuclear factor-kappaB (NF-kappaB) by lipid ozonation products is crucial to interleukin-8 gene expression in human airway epithelial cells.

    PubMed

    Kafoury, Ramzi M; Hernandez, Jazmir M; Lasky, Joseph A; Toscano, William A; Friedman, Mitchell

    2007-04-01

    Ozone (O(3)) is a major component of smog and an inhaled toxicant to the lung. O(3) rapidly reacts with the airway epithelial cell membrane phospholipids to generate lipid ozonation products (LOP). 1-Hydroxy-1-hydroperoxynonane (HHP-C9) is an important LOP, produced from the ozonation of 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphatidylcholine. This LOP, at a biologically relevant concentration (100 microM), increases the activity of phospholipase C, nuclear factors-kappaB (NF-kappaB), and interleukin-6 (NF-IL-6) and the expression of the inflammatory gene, interleukin-8 (IL-8) in a cultured human bronchial epithelial cell line (BEAS-2B). The signaling pathways of ozone and its biologically-active products are as yet undefined. In the present study, we report that the HHP LOP, HHP-C9 (100 microM x 4 h), activated the expression of IL-8 (218 +/- 26% increase over control, n = 4, P < 0.01) through an apparent interaction between the two transcription factors, NF-kappaB and NF-IL-6. Transfection studies using luciferase reporter assays demonstrated that HHP-C9 induced a significant increase in NF-kappaB-DNA binding activity (37 +/- 7% increase over control, n = 6, P < 0.05). Inhibition of NF-kappaB showed a statistically significant but modest decrease in IL-8 release, which suggested a role for another transcription factor, NF-IL-6. Exposure of BEAS-2B cells to HHP-C9 induced a significant increase in the DNA binding activity of NF-IL-6 (45 +/- 11% increase over control, n = 6, P < 0.05). The results of the present study indicate that NF-IL-6 interacts with NF-kappaB in regulating the expression of IL-8 in cultured human airway epithelial cells exposed to LOP, the biological products of ozone in the lung. PMID:17366569

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

    SciTech Connect

    Benyhe, S.; Varga, E.; Hepp, J.; Magyar, A.; Borsodi, A.; Wollemann, M.

    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. 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.

  10. Stage-dependent agreement between cerebrospinal fluid proteins and FDG-PET findings in Alzheimer's disease.

    PubMed

    Yakushev, Igor; Muller, Matthias J; Buchholz, Hans-Georg; Lang, Ulrike; Rossmann, Heidi; Hampel, Harald; Schreckenberger, Mathias; Fellgiebel, Andreas

    2012-02-01

    Cerebral hypometabolism and abnormal levels of amyloid beta (Aβ), total (t-tau) and phosphorylated tau (ptau) proteins in cerebrospinal fluid (CSF) are established biomarkers of Alzheimer's disease (AD). We examined the agreement between these biomarkers in a single center study of patients with AD of severity extending over a wide range. Forty seven patients (MMSE 21.4 ± 3.6, range 13-28 points) with incipient and probable AD underwent positron emission tomography with [18F]-fluorodeoxyglucose (FDG-PET) and lumbar puncture for CSF assays of Aβ1-42, p-tau181, and t-tau. All findings were classified as either positive or negative for AD. Statistical analyses were performed for the whole sample (n=47) and for the subgroups stratified as mild (MMSE > 20 points, n=30) and moderate (MMSE < 21 points, n=17) AD. In the whole patient sample, the agreement with the FDG-PET finding was 77% (chance-corrected kappa [κ]=0.34, p=0.016) for t-tau, 68% (κ=0.10, n.s.) for p-tau181, and 68% (κ=0.04, n.s.) for Aβ1-42. No significant agreement was found in the mild AD subgroup, while there was a strong agreement for t-tau (94%, κ=0.77, p=0.001) and p-tau181 (88%, κ=0.60, p=0.014) in the moderate AD group. A significant agreement between the FDG-PET and CSF tau findings in patients with AD supports the view that both are markers of neurodegeneration. CSF tau proteins and FDG-PET might substitute each other as supportive diagnostic tools in patients with suspected moderate-to-severe Alzheimer's dementia, while this is not the case in subjects at an earlier disease stage. PMID:22044023

  11. Electronic portal imaging registration in breast cancer radiotherapy verification: analysis of inter-observer agreement among different categories of health practitioners.

    PubMed

    Jereczek-Fossa, B A; Santoro, L; Colangione, S P; Morselli, L; Fodor, C; Vischioni, B; Rozza, D; Leppa, A; Cambria, R; Leonardi, M C; Morra, A; Baroni, G; Zurrida, S; Orecchia, R

    2013-01-01

    Electronic portal imaging (EPI) is commonly used to identify and correct for inter-fraction variability in tangential breast irradiation. Based on the institutional policy, EPI registration is performed by either radiation oncologist or therapist. Little data is available on the inter-observer agreement in EPI registration among different health practitioners. The aim of our study was to analyze inter-observer agreement among radiation oncologists and therapists in the evaluation of EPI for breast cancer radiotherapy verification. EPI data of 40 patients treated with tangential fields were independently reviewed by a radiation oncologist (on-line, just before treatment) and off-line by junior and senior therapists. Displacement of each EPI image with respect to the digital reconstructed radiographs (DRRs) was quantified using manual EPI registration based on bony marks with the corresponding DRRs. Agreement between observers was evaluated using weighted Cohen's Kappa statistics. In 95% out of 720 EPI-DRR comparisons, the EPI-DRR misalignment was < 5 mm. The difference between observers was < 2 mm in 666 (92.5%) out of all 720 delta values. High inter-observer agreement was found, with weighted Cohen's Kappa values attesting evaluation overlaps ranging from moderate (among therapists) to almost perfect (among radiation oncologist and therapists). The high agreement among the observers demonstrated the precision of breast localization using EPI. These findings suggest that routine EPI-based patient set-up verification in breast cancer radiotherapy can be safely entrusted to trained therapists (supervision should be assured based on the local tasks definition). Our study might be useful in quality assurance and in the optimization of workload in the radiotherapy departments. They might allow for wider implementation of complex and evolving radiotherapy technologies. PMID:23374000

  12. Poor agreement between self-reported diagnosis and bone mineral density results in the identification of osteoporosis.

    PubMed

    Stuart, Amanda L; Williams, Lana J; Brennan, Sharon L; Kotowicz, Mark A; Pasco, Julie A

    2015-01-01

    Osteoporosis is a major health concern, estimated to affect millions worldwide. Bone mineral density (BMD) assessment is not practical for many large-scale epidemiological studies resulting in the reliance of self-report methods to ascertain diagnostic information. The aim of the study was to assess the validity of self-reported diagnosis of osteoporosis in a population-based study. This study examined data collected from 906 men and 843 women participating in the Geelong Osteoporosis Study. Osteoporosis was self-reported and compared against results of BMD scans of the hip and spine. Validity was examined by calculating sensitivity, specificity, positive predictive value, negative predictive value, and kappa statistic. Osteoporosis was self-reported by 118 (6.7%) participants and identified using BMD results for 64 (3.7%) participants. Specificity and negative predictive value were good (95.1% and 96.0%, respectively), whereas sensitivity and positive predictive value were poor (35.9% and 31.4%, respectively). The overall level of agreement (kappa) was 0.29. The results changed only slightly when we included participants with osteopenia and adult fracture as osteoporotic. Reliance on self-report methods to ascertain osteoporosis status is not recommended. PMID:24912958

  13. Effects of radiation on tumor hemodynamics and NF-kappaB in breast tumors

    NASA Astrophysics Data System (ADS)

    Stantz, Keith M.; Cao, Ning; Liu, Bo; Cao, Minsong; Chin-Sinex, Helen; Mendonca, Marc; Li, Jian Jian

    2010-02-01

    Purpose: The purpose of this study is to monitor in vivo the IR dose dependent response of NF-κB and tumor hemodynamics as a function of time. Material and Methods: An MDA-231 breast cancer cell line was stably transfected with a firefly luciferase gene within the NF-kappaB promoter. Tumors on the right flank irradiated with a single fractionated dose of 5Gy or 10Gy. Over two weeks, photoacoustic spectroscopy (PCT-S), bioluminescence imaging (BLI), and dynamic contrast enhanced CT (DCE-CT) was used to monitor hemoglobin status, NF-kappaB expression, and physiology, respectively. Results: From the BLI, an increase in NF-kappaB expression was observed in both the right (irradiation) and left (nonirradiated) tumors, which peaked at 8-12 hours, returned to basal levels after 24 hours, and increased a second time from 3 to 7 days. This data identifies both a radiation-induced bystander effect and a bimodal longitudinal response associated with NF-κB-controlled luciferase promoter. The physiological results from DCE-CT measured an increase in perfusion (26%) two days after radiation and both a decrease in perfusion and an increase in fp by week 1 (10Gy cohort). PCT-S measured increased levels of oxygen saturation two days post IR, which did not change after 1 week. Initially, NF-κB would modify hemodynamics to increase oxygen delivery after IR insult. The secondary response appears to modulate tumor angiogenesis. Conclusions: A bimodal response to radiation was detected with NF-kappaB-controlled luciferase reporter with a concomitant hemodynamic response associated with tumor hypoxia. Experiments are being performed to increase statistics.

  14. Involvement of kappa type opioids on ethanol drinking

    SciTech Connect

    Sandi, C.; Borrell, J.; Guaza, C.

    1988-01-01

    The effects of the administration of the kappa agonist dynorphin/sub 1/..sqrt../sub 17/ andor the kappa antagonist MR-2266-BS on ethanol preference was investigated using a paradigm by which rats develop alcohol preference. Administration of dynorphin shortly before or after the conditioning session (forced ethanol exposure) failed to affect later ethanol preference. However, dynorphin treatment prior to the first choice session reduced ethanol preference during the three consecutive testing days. This effect was reversed by the simultaneous administration of the kappa antagonist MR-2266-BS. The results of the present study provide further support for evidence of the involvement of dynorphinergic systems on drinking behavior and suggest that kappa-type opioid mechanisms may be involved in the consumption and development of preference to ethanol in rats. 32 references, 3 figures, 2 tables

  15. Curie law for systems described by kappa distributions

    NASA Astrophysics Data System (ADS)

    Livadiotis, George

    2016-01-01

    We derive the magnetization of a system, Pierre Curie's law, for paramagnetic particles out of thermal equilibrium described by kappa distributions. The analysis uses the theory and formulation of the kappa distributions that describe particle systems with a non-zero potential energy. Among other results, emphasis is placed on the effect of kappa distribution on the phenomenon of having strong magnetization at high temperatures. At thermal equilibrium, high temperature leads to weak magnetization. Out of thermal equilibrium, however, strong magnetization at high temperatures is rather possible, if the paramagnetic particle systems reside far from thermal equilibrium, i.e., at small values of kappa. The application of the theory to the space plasma at the outer boundaries of our heliosphere, the inner heliosheath, leads to an estimation of the ion magnetic moment for this space plasma, that is, μ ≈ 138+/-7 \\text{eV/nT} .

  16. Electrodynamics on {kappa}-Minkowski space-time

    SciTech Connect

    Harikumar, E.; Juric, T.; Meljanac, S.

    2011-10-15

    In this paper, we derive Lorentz force and Maxwell's equations on kappa-Minkowski space-time up to the first order in the deformation parameter. This is done by elevating the principle of minimal coupling to noncommutative space-time. We also show the equivalence of minimal coupling prescription and Feynman's approach. It is shown that the motion in kappa space-time can be interpreted as motion in a background gravitational field, which is induced by this noncommutativity. In the static limit, the effect of kappa deformation is to scale the electric charge. We also show that the laws of electrodynamics depend on the mass of the charged particle, in kappa space-time.

  17. Obliquely Propagating Electromagnetic Waves in Magnetized Kappa Plasmas

    NASA Astrophysics Data System (ADS)

    Gaelzer, R.

    2015-12-01

    The effects of velocity distribution functions (VDFs) that exhibit a power-law dependence on the high-energy tail have been the subjectof intense research by the space plasma community. Such functions, known as kappa or superthermal distributions, have beenfound to provide a better fitting to the VDF measured by spacecraft in the solar wind. One of the problems that is being addressed on this new light is the temperature anisotropy of solar wind protons and electrons. An anisotropic kappa VDF contains a large amount of free energy that can excite waves in the solar wind. Conversely, the wave-particle interaction is important to determine the shape of theobserved particle distributions.In the literature, the general treatment for waves excited by (bi-)Maxwellian plasmas is well-established. However, for kappa distributions, either isotropic or anisotropic, the wave characteristics have been studied mostly for the limiting cases of purely parallel or perpendicular propagation. Contributions for the general case of obliquely-propagating electromagnetic waves have been scarcely reported so far. The absence of a general treatment prevents a complete analysis of the wave-particle interaction in kappa plasmas, since some instabilities, such as the firehose, can operate simultaneously both in the parallel and oblique directions.In a recent work [1], we have obtained expressions for the dielectric tensor and dispersion relations for the low-frequency, quasi-perpendicular dispersive Alfvén waves resulting from a kappa VDF. In the present work, we generalize the formalism introduced by [1] for the general case of electrostatic and/or electromagnetic waves propagating in a kappa plasma in any frequency range and for arbitrary angles.We employ an isotropic distribution, but the methods used here can be easily applied to more general anisotropic distributions,such as the bi-kappa or product-bi-kappa. [1] R. Gaelzer and L. F. Ziebell, Journal of Geophysical Research 119, 9334

  18. Grader agreement, and sensitivity and specificity of digital photography in a community optometry-based diabetic eye screening program

    PubMed Central

    Sellahewa, Luckni; Simpson, Craig; Maharajan, Prema; Duffy, John; Idris, Iskandar

    2014-01-01

    Background Digital retinal photography with mydriasis is the preferred modality for diabetes eye screening. The purpose of this study was to evaluate agreement in grading levels between primary and secondary graders and to calculate their sensitivity and specificity for identifying sight-threatening disease in an optometry-based retinopathy screening program. Methods This was a retrospective study using data from 8,977 patients registered in the North Nottinghamshire retinal screening program. In all cases, the ophthalmology diagnosis was used as the arbitrator and considered to be the gold standard. Kappa statistics were used to evaluate the level of agreement between graders. Results Agreement between primary and secondary graders was 51.4% and 79.7% for detecting no retinopathy (R0) and background retinopathy (R1), respectively. For preproliferative (R2) and proliferative retinopathy (R3) at primary grading, agreement between the primary and secondary grader was 100%. Where there was disagreement between the primary and secondary grader for R1, only 2.6% (n=41) were upgraded by an ophthalmologist. The sensitivity and specificity for detecting R3 was 78.2% and 98.1%, respectively. None of the patients upgraded from any level of retinopathy to R3 required photocoagulation therapy. The observed kappa between the primary and secondary grader was 0.3223 (95% confidence interval 0.2937–0.3509), ie, fair agreement, and between the primary grader and ophthalmology for R3 was 0.5667 (95% confidence interval 0.4557–0.6123), ie, moderate agreement. Conclusion These data provide information on the safety of a community optometry-based retinal screening program for screening as a primary and as a secondary grader. The level of agreement between the primary and secondary grader at a higher level of retinopathy (R2 and R3) was 100%. Sensitivity and specificity for R3 were 78.2% and 98.1%, respectively. None of the false-negative results required photocoagulation therapy

  19. Kappa Opioids, Salvinorin A and Major Depressive Disorder

    PubMed Central

    Taylor, George T.; Manzella, Francesca

    2016-01-01

    Opioids are traditionally associated with pain, analgesia and drug abuse. It is now clear, however, that the opioids are central players in mood. The implications for mood disorders, particularly clinical depression, suggest a paradigm shift from the monoamine neurotransmitters to the opioids either alone or in interaction with monoamine neurons. We have a special interest in dynorphin, the last of the major endogenous opioids to be isolated and identified. Dynorphin is derived from the Greek word for power, dynamis, which hints at the expectation that the neuropeptide held for its discoverers. Yet, dynorphin and its opioid receptor subtype, kappa, has always taken a backseat to the endogenous b-endorphin and the exogenous morphine that both bind the mu opioid receptor subtype. That may be changing as the dynorphin/ kappa system has been shown to have different, often opposite, neurophysiological and behavioral influences. This includes major depressive disorder (MDD). Here, we have undertaken a review of dynorphin/ kappa neurobiology as related to behaviors, especially MDD. Highlights include the unique features of dynorphin and kappa receptors and the special relation of a plant-based agonist of the kappa receptor salvinorin A. In addition to acting as a kappa opioid agonist, we conclude that salvinorin A has a complex pharmacologic profile, with potential additional mechanisms of action. Its unique neurophysiological effects make Salvinorina A an ideal candidate for MDD treatment research. PMID:26903446

  20. Multipurpose ligand, DAKLI (Dynorphin A-analogue Kappa LIgand), with high affinity and selectivity for dynorphin (. kappa. opioid) binding sites

    SciTech Connect

    Goldstein, A.; Nestor, J.J. Jr.; Naidu, A.; Newman, S.R. )

    1988-10-01

    The authors describe a synthetic ligand, DALKI (Dynorphin A-analogue Kappa LIgand), related to the opioid peptide dynorphin A. A single reactive amino group at the extended carboxyl terminus permits various reporter groups to be attached, such as {sup 125}I-labeled Bolton-Hunter reagent, fluorescein isothiocyanate, or biotin. These derivatives have high affinity and selectivity for the dynorphin ({kappa} opioid) receptor. An incidental finding is that untreated guinea pig brain membranes have saturable avidin binding sites.

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

    SciTech Connect

    Wang Zhi; Kang Jinsong; Li Yang; Yuan Zhaoxin; Liu Shanshan; Sun Liankun . E-mail: sunlk@jlu.edu.cn

    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 activity 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.

  2. [Inter-observes agreement of Ishak and Metavir scores in histological evaluation of chronic viral hepatitis B and C].

    PubMed

    Rammeh, Soumaya; Khadra, Hajer Ben; Znaidi, Nadia Sabbegh; Romdhane, Neila Attia; Najjar, Taoufik; Bouzaidi, Slim; Zermani, Rachida

    2014-01-01

    Many classification systems are currently used for histological evaluation of the severity of chronic viral hepatitis, including the Ishak and Metavir scores, but there is not a consensus classification. The objective of this work was to study the intra and inter-observers agreement of these two scores in the histopathological analysis of liver biopsies in patients with chronic viral hepatitis B or C. Fifty nine patients were included in the study, 26 had chronic hepatitis C and 33 had chronic hepatitis B. To investigate the inter-observers agreement, the liver biopsies were analyzed separately by two pathologists without prior consensus reading. The two pathologists conducted then a consensual reading before reviewing all cases independently. Cohen's kappa coefficient was calculated and in case of asymmetry Spearman's rho coefficient. Before the consensus reading, the agreement was moderate for the analysis of histological activity with both scores (Metavir: kappa=0.41, Ishak: rho=0.58). For the analysis of fibrosis, the agreement was good with both scores (Metavir: kappa=0.61, Ishak: rho=0.86). The consensus reading has improved the reproducibility of the activity that has become good with both scores (Metavir: kappa=0.77, Ishak: rho=0.76). For fibrosis improvement was observed with the Ishak score which agreement became excellent (kappa=0.81). In conclusion, we recommend in routine practice, a combined score: Metavir for activity and Ishak for fibrosis and to make a double reading for each biopsy.

  3. Vascular endothelial growth factor signalling in endothelial cell survival: A role for NF{kappa}B

    SciTech Connect

    Grosjean, Jennifer . E-mail: Jennifer.grosjean@imperial.ac.uk; Kiriakidis, Serafim; Reilly, Kerri; Feldmann, Marc; Paleolog, Ewa

    2006-02-17

    Angiogenesis is the development of blood capillaries from pre-existing vessels. Vascular endothelial growth factor (VEGF) is a key regulator of vessel growth and regression, and acts as an endothelial survival factor by protecting endothelial cells from apoptosis. Many genes involved in cell proliferation and apoptosis are regulated by the nuclear factor kappa B (NF{kappa}B) transcription factor family. This study aimed to address the hypothesis that VEGF-mediated survival effects on endothelium involve NF{kappa}B. Using an NF{kappa}B-luciferase reporter adenovirus, we observed activation of NF{kappa}B following VEGF treatment of human umbilical vein endothelial cells. This was confirmed using electrophoretic mobility shift assay and found to involve nuclear translocation of NF{kappa}B sub-unit p65. However, NF{kappa}B activation occurred without degradation of inhibitory I{kappa}B proteins (I{kappa}B{alpha}, I{kappa}B{beta}, and I{kappa}B{epsilon}). Instead, tyrosine phosphorylation of I{kappa}B{alpha} was observed following VEGF treatment, suggesting NF{kappa}B activation was mediated by degradation-independent dissociation of I{kappa}B{alpha} from NF{kappa}B. Adenovirus-mediated over-expression of either native I{kappa}B{alpha}, or of I{kappa}B{alpha} in which tyrosine residue 42 was mutated to phenylalanine, inhibited induction of NF{kappa}B-dependent luciferase activity in response to VEGF. Furthermore, VEGF-induced upregulation of mRNA for the anti-apoptotic protein Bcl-2 and cell survival following serum withdrawal was reduced following I{kappa}B{alpha} over-expression. This study highlights that different molecular mechanisms of NF{kappa}B activation may be involved downstream of stimuli which activate the endothelial lining of blood vessels.

  4. Agreement between Patient and Proxy Assessments of Quality of Life among Older Adults with Vascular Cognitive Impairment Using the EQ-5D-3L and ICECAP-O

    PubMed Central

    Davis, Jennifer C.; Hsiung, Ging-Yuek; Bryan, Stirling; Jacova, Claudia; Jacova, Patrizio; Munkacsy, Michelle; Cheung, Winnie; Lee, Philip; Liu-Ambrose, Teresa

    2016-01-01

    Background The assessment of quality of life is critical in ascertaining the benefit of interventions aimed to reduce morbidity among individuals with cognitive impairment. However, the assessment of quality of life is challenging in this population due to the uncertain validity of patient responses as cognitive function declines. Hence, we examined the level of agreement between patient and proxy assessments of health related quality of life (HRQoL) and wellbeing based on the domains that comprise each of these constructs. Methods Analysis of baseline data from 71 community-dwelling older adults with mild Vascular Cognitive Impairment (VCI) who participated in a six-month proof-of-concept single-blinded randomized trial. Level of agreement between patient and caregiver ratings of HRQoL (EQ-5D-3L) and wellbeing (ICECAP-O) were compared using raw agreement (%), intraclass correlation coefficient (ICC) and weighted Cohen’s kappa statistic. Results Self-care (assessed via the EQ-5D-3L) demonstrated almost perfect raw agreement between the patient and caregiver ratings. Three domains (mobility, pain and anxiety) of the EQ-5D-3L demonstrated fair agreement between the patient and caregiver ratings. Two (attachment and control) of the five ICECAP-O domains demonstrated slight agreement. The ICC indicated good agreement for the EQ-5D-3L and poor agreement for the ICECAP-O. Conclusion There is better patient-proxy agreement for the EQ-5D-3L compared with the ICECAP-O among individuals with mild VCI. These findings imply that the ICECAP-O may have limited clinical, research and policy related utility among individuals with mild VCI. Trial Registration ClinicalTrials.gov NCT01027858 PMID:27101402

  5. Obliquely propagating electromagnetic waves in magnetized kappa plasmas

    NASA Astrophysics Data System (ADS)

    Gaelzer, R.; Ziebell, L. F.

    2016-02-01

    Velocity distribution functions (VDFs) that exhibit a power-law dependence on the high-energy tail have been the subject of intense research by the plasma physics community. Such functions, known as kappa or superthermal distributions, have been found to provide a better fitting to the VDFs measured by spacecraft in the solar wind. One of the problems that is being addressed on this new light is the temperature anisotropy of solar wind protons and electrons. In the literature, the general treatment for waves excited by (bi-)Maxwellian plasmas is well-established. However, for kappa distributions, the wave characteristics have been studied mostly for the limiting cases of purely parallel or perpendicular propagation, relative to the ambient magnetic field. Contributions to the general case of obliquely propagating electromagnetic waves have been scarcely reported so far. The absence of a general treatment prevents a complete analysis of the wave-particle interaction in kappa plasmas, since some instabilities can operate simultaneously both in the parallel and oblique directions. In a recent work, Gaelzer and Ziebell [J. Geophys. Res. 119, 9334 (2014)] obtained expressions for the dielectric tensor and dispersion relations for the low-frequency, quasi-perpendicular dispersive Alfvén waves resulting from a kappa VDF. In the present work, the formalism is generalized for the general case of electrostatic and/or electromagnetic waves propagating in a kappa plasma in any frequency range and for arbitrary angles. An isotropic distribution is considered, but the methods used here can be easily applied to more general anisotropic distributions such as the bi-kappa or product-bi-kappa.

  6. Interobserver agreement among cytopathologists in the evaluation of pancreatic endoscopic ultrasound-guided fine needle aspiration cytology specimens*

    PubMed Central

    Mounzer, Rawad; Yen, Roy; Marshall, Carrie; Sams, Sharon; Mehrotra, Sanjana; Said, Mohamed Sherif; Obuch, Joshua C.; Brauer, Brian; Attwell, Augustin; Fukami, Norio; Shah, Raj; Amateau, Stuart; Hall, Matthew; Hosford, Lindsay; Wilson, Robert; Rastogi, Amit; Wani, Sachin

    2016-01-01

    Background and aims: Endoscopic ultrasound with fine needle aspiration (EUS-FNA) has become the standard of care in the evaluation of solid pancreatic lesions. Limited data exist on interobserver agreement (IOA) among cytopathologists in assessing solid pancreatic EUS-FNA specimens. This study aimed to evaluate IOA among cytopathologists in assessing EUS-FNA cytology specimens of solid pancreatic lesions using a novel standardized scoring system and to assess individual clinical and cytologic predictors of IOA. Methods: Consecutive patients who underwent EUS-FNA of solid pancreatic lesions at a tertiary care referral center were included. EUS-FNA slides were evaluated by four blinded cytopathologists using a standardized scoring system that assessed final cytologic diagnosis and quantitative (number of nucleated/diagnostic cells) and qualitative (bloodiness, inflammation/necrosis, contamination, artifact) cytologic parameters. Final clinical diagnosis was based on final cytology, surgical pathology, or 1-year clinical follow-up. IOA was calculated using multi-rater kappa (κ) statistics. Bivariate analyses were performed comparing cases with and without uniform agreement among the cytopathologists followed by logistic regression with backward elimination to model likelihood of uniform agreement. Results: Ninety-nine patients were included (49 % males, mean age 64 years, mean lesion size 26 mm). IOA for final diagnosis was moderate (κ = 0.45, 95 % confidence interval (CI) 0.4 – 0.49) with minimal improvement when combining suspicious and malignant diagnoses (κ = 0.54, 95 %CI 0.49 – 0.6). The weighted kappa value for overall diagnosis was 0.65 (95 %CI 0.54 – 0.76). IOA was slight to fair (κ = 0.04 – 0.32) for individual cytologic parameters. A final clinical diagnosis of malignancy was the most significant predictor of agreement [OR 3.99 (CI 1.52 – 10.49)]. Conclusions: Interobserver agreement among

  7. Application of a new time scale based low {kappa}-{var_epsilon} model to natural convection from a semi-infinite vertical isothermal plate

    SciTech Connect

    Woods, A.L.; Senthooran, S.; Parameswaran, S.

    1999-01-01

    The low {kappa}-{var_epsilon} model proposed by Yang and Shih (1992) is applied to the calculation of the turbulent natural convective boundary layer over a semi-infinite, vertical, isothermal surface. Using {kappa}/{var_epsilon} as the turbulent time scale will introduce a singularity in the {var_epsilon} equation, near the wall. This model uses a modified turbulent time scale near the wall to eliminate this singularity. The constants in the equation for damping function are modified to produce better results for both, natural convection and force convection. The results are compared with available experimental data and the results obtained from Chien`s model and are found to be in reasonable agreement. Here {kappa} represents the turbulent kinetic energy and {var_epsilon} represents the dissipation rate of turbulent kinetic energy.

  8. Reliability of groundwater vulnerability maps obtained through statistical methods.

    PubMed

    Sorichetta, Alessandro; Masetti, Marco; Ballabio, Cristiano; Sterlacchini, Simone; Beretta, Giovanni Pietro

    2011-04-01

    Statistical methods are widely used in environmental studies to evaluate natural hazards. Within groundwater vulnerability in particular, statistical methods are used to support decisions about environmental planning and management. The production of vulnerability maps obtained by statistical methods can greatly help decision making. One of the key points in all of these studies is the validation of the model outputs, which is performed through the application of various techniques to analyze the quality and reliability of the final results and to evaluate the model having the best performance. In this study, a groundwater vulnerability assessment to nitrate contamination was performed for the shallow aquifer located in the Province of Milan (Italy). The Weights of Evidence modeling technique was used to generate six model outputs, each one with a different number of input predictive factors. Considering that a vulnerability map is meaningful and useful only if it represents the study area through a limited number of classes with different degrees of vulnerability, the spatial agreement of different reclassified maps has been evaluated through the kappa statistics and a series of validation procedures has been proposed and applied to evaluate the reliability of the reclassified maps. Results show that performance is not directly related to the number of input predictor factors and that is possible to identify, among apparently similar maps, those best representing groundwater vulnerability in the study area. Thus, vulnerability maps generated using statistical modeling techniques have to be carefully handled before they are disseminated. Indeed, the results may appear to be excellent and final maps may perform quite well when, in fact, the depicted spatial distribution of vulnerability is greatly different from the actual one. For this reason, it is necessary to carefully evaluate the obtained results using multiple statistical techniques that are capable of

  9. Interaction between plasma and low-kappa dielectric materials

    NASA Astrophysics Data System (ADS)

    Bao, Junjing

    With the scaling of devices, integration of porous ultra low-kappa dielectric materials into Cu interconnect becomes necessary. Low-kappa dielectric materials usually consist of a certain number of methyl groups and pores incorporated into a SiO2 backbone structure to reduce the dielectric constant. They are frequently exposed to various plasmas, since plasma is widely used in VLSI semiconductor fabrication such as etching, ashing and deposition. This dissertation is aimed at exploring the interaction between plasma and low-kappa dielectric surfaces. First, plasma assisted the atomic layer deposition (ALD) of Ta-based Cu barriers. Atomic layer deposition of Ta barriers is a self-limited surface reaction, determined by the function groups on the low-kappa dielectric surface. But it was found TaCl5 precursor could not nucleate on the organosilicate low-kappa surface that was terminated with methyl groups. Radical NHx beam, generated by a microwave plasma source, could activate the surface through exchanging with the methyl groups on the low-kappa surface and providing active Si-NHx nucleation sites for TaCl 5 precursors. Results from Monte Carlo simulation of the atomic layer deposition demonstrated that substrate chemistry was critical in controlling the film morphology. Second, the properties of low-kappa dielectric materials tended to degrade under plasma exposure. In this dissertation, plasma damage of low-kappa dielectric surface was investigated from a mechanistic point of view. Both carbon depletion and surface densification were observed on the top surface of damaged low-kappa materials while the bulk remained largely uninfluenced. Plasma damage was found to be a complicated phenomenon involving both chemical and physical effects, depending on chemical reactivity and the energy and mass of the plasma species. With a downstream plasma source capable of separating ions from the plasma beam and an in-situ x-ray photoelectron spectroscopy (XPS) monitoring of the

  10. A Measure of Agreement for Interval or Nominal Multivariate Observations by Different Sets of Judges

    ERIC Educational Resources Information Center

    Janson, Harald; Olsson, Ulf

    2004-01-01

    This article addresses the problem of accounting overall multivariate chance-corrected interobserver agreement when targets have been rated by different sets of judges (not necessarily equal in number). The proposed approach builds on Janson and Olsson's multivariate generalization of Cohen's kappa but incorporates weighting for number of judges…

  11. Nuclear factor-kappa B links carcinogenic and chemopreventive agents.

    PubMed

    Ralhan, Ranju; Pandey, Manoj K; Aggarwal, Bharat B

    2009-01-01

    Cancer prevention requires avoidance of tobacco, alcohol, high-fat diet, polluted air and water, sedentary lifestyle, and of mechanical, physical, psychological, or chemical stress. How these factors can cause cancer, is suggested by the transcription nuclear factor-kappa B (NF-kappa B), that is activated by tobacco, alcohol, high-fat diet, environment pollutants, cancer-causing viruses (human papillomavirus, hepatitis B and C viruses, HIV) and bacteria (Helicobacter pylori), ultraviolet light, ionizing radiation, obesity, and stress. Furthermore, NF-kappa B-regulated gene products have been implicated in transformation of cells, and in proliferation, survival, invasion, angiogenesis, and metastasis. Suppression of NF-kappa B activation by the phytochemicals present in fruits and vegetables provides the molecular basis for their ability to prevent cancer. Other agents identified from spices and Ayurvedic and traditional Chinese medicines also been found to suppress NF-kappa B activation and thus may have potential for cancer prevention. The classic chemopreventive agent should offer long-term safety, low cost, and efficacy. The current review discuses in detail numerous agents such as curcumin, resveratrol, silymarin, catechins and others as potential chemopreventive agents. Thus, cancer, an ancient problem, may have an ancient solution. PMID:19482682

  12. Nuclear factor-kappa B signaling in skeletal muscle atrophy.

    PubMed

    Li, Hong; Malhotra, Shweta; Kumar, Ashok

    2008-10-01

    Skeletal muscle atrophy/wasting is a serious complication of a wide range of diseases and conditions such as aging, disuse, AIDS, chronic obstructive pulmonary disease, space travel, muscular dystrophy, chronic heart failure, sepsis, and cancer. Emerging evidence suggests that nuclear factor-kappa B (NF-kappaB) is one of the most important signaling pathways linked to the loss of skeletal muscle mass in various physiological and pathophysiological conditions. Activation of NF-kappaB in skeletal muscle leads to degradation of specific muscle proteins, induces inflammation and fibrosis, and blocks the regeneration of myofibers after injury/atrophy. Recent studies employing genetic mouse models have provided strong evidence that NF-kappaB can serve as an important molecular target for the prevention of skeletal muscle loss. In this article, we have outlined the current understanding regarding the role of NF-kappaB in skeletal muscle with particular reference to different models of muscle wasting and the development of novel therapy.

  13. Cloning and pharmacological characterization of a rat kappa opioid receptor.

    PubMed Central

    Meng, F; Xie, G X; Thompson, R C; Mansour, A; Goldstein, A; Watson, S J; Akil, H

    1993-01-01

    A full-length cDNA was isolated from a rat striatal library by using low-stringency screening with two PCR fragments, one spanning transmembrane domains 3-6 of the mouse delta opioid receptor and the other unidentified but homologous to the mouse delta receptor from rat brain. The novel cDNA had a long open reading frame encoding a protein of 380 residues with 59% identity to the mouse delta receptor and topography consistent with a seven-helix guanine nucleotide-binding protein-coupled receptor. COS-1 cells transfected with the coding region of this clone showed high-affinity binding to kappa opioid receptor-selective ligands such as dynorphin A and U-50,488 and also nonselective opioid ligands such as bremazocine, ethylketocyclazocine, and naloxone. Not bound at all (or bound with low affinity) were dynorphin A-(2-13), enantiomers of naloxone and levophanol [i.e., (+)-naloxone and dextrorphan], and selective mu and delta opioid receptor ligands. Activation of the expressed receptor by kappa receptor agonists led to inhibition of cAMP. Finally, in situ hybridization revealed a mRNA distribution in rat brain that corresponded well to the distribution of binding sites labeled with kappa-selective ligands. These observations indicate that we have cloned a cDNA encoding a rat kappa receptor of the kappa 1 subtype. Images Fig. 3 PMID:8234341

  14. Numerical solution of High-kappa model of superconductivity

    SciTech Connect

    Karamikhova, R.

    1996-12-31

    We present formulation and finite element approximations of High-kappa model of superconductivity which is valid in the high {kappa}, high magnetic field setting and accounts for applied magnetic field and current. Major part of this work deals with steady-state and dynamic computational experiments which illustrate our theoretical results numerically. In our experiments we use Galerkin discretization in space along with Backward-Euler and Crank-Nicolson schemes in time. We show that for moderate values of {kappa}, steady states of the model system, computed using the High-kappa model, are virtually identical with results computed using the full Ginzburg-Landau (G-L) equations. We illustrate numerically optimal rates of convergence in space and time for the L{sup 2} and H{sup 1} norms of the error in the High-kappa solution. Finally, our numerical approximations demonstrate some well-known experimentally observed properties of high-temperature superconductors, such as appearance of vortices, effects of increasing the applied magnetic field and the sample size, and the effect of applied constant current.

  15. Agreement between the SCORE and D’Agostino Scales for the Classification of High Cardiovascular Risk in Sedentary Spanish Patients

    PubMed Central

    Gómez-Marcos, Manuel A.; Grandes, Gonzalo; Iglesias-Valiente, José A.; Sánchez, Alvaro; Montoya, Imanol; García-Ortiz, Luis

    2009-01-01

    Background: To evaluate agreement between cardiovascular risk in sedentary patients as estimated by the new Framingham-D’Agostino scale and by the SCORE chart, and to describe the patient characteristics associated with the observed disagreement between the scales. Design: A cross-sectional study was undertaken involving a systematic sample of 2,295 sedentary individuals between 40–65 years of age seen for any reason in 56 primary care offices. An estimation was made of the Pearson correlation coefficient and kappa statistic for the classification of high risk subjects (≥20% according to the Framingham-D’Agostino scale, and ≥5% according to SCORE). Polytomous logistic regression models were fitted to identify the variables associated with the discordance between the two scales. Results: The mean risk in males (35%) was 19.5% ± 13% with D’Agostino scale, and 3.2% ± 3.3% with SCORE. Among females, they were 8.1% ± 6.8% and 1.2% ± 2.2%, respectively. The correlation between the two scales was 0.874 in males (95% CI: 0.857–0.889) and 0.818 in females (95% CI: 0.800–0.834), while the kappa index was 0.50 in males (95% CI: 0.44%–0.56%) and 0.61 in females (95% CI: 0.52%–0.71%). The most frequent disagreement, characterized by high risk according to D’Agostino scale but not according to SCORE, was much more prevalent among males and proved more probable with increasing age and increased LDL-cholesterol, triglyceride and systolic blood pressure values, as well as among those who used antihypertensive drugs and smokers. Conclusions: The quantitative correlation between the two scales is very high. Patient categorization as corresponding to high risk generates disagreements, mainly among males, where agreement between the two classifications is only moderate. PMID:20049225

  16. Crystal structure of kappa-In2Se3

    SciTech Connect

    Jasinski, J.; Swider, W.; Washburn, J.; Liliental-Weber, Z.; Chaiken, A.; Nauka, K.; Gibson, G.A.; Yang, C.C.

    2002-10-24

    Structural properties of single-phase films of {kappa}-In{sub 2}Se{sub 3} and {gamma}-In{sub 2}Se{sub 3} were investigated. Both films were polycrystalline but their microstructure differed considerably. The a-lattice parameter of {kappa}-In{sub 2}Se{sub 3} has been measured. Comparison between these two materials indicates that {kappa}-In{sub 2}Se{sub 3} has a significantly larger unit cell ({Delta}c = 2.5 {+-} 0.2 % and {Delta}a = 13.5 {+-} 0.5%) and a structure more similar to the {alpha}-phase of In{sub 2}Se{sub 3}.

  17. Cdc25A promotes cell survival by stimulating NF-{kappa}B activity through I{kappa}B-{alpha} phosphorylation and destabilization

    SciTech Connect

    Hong, Hey-Young; Choi, Jiyeon; Cho, Young-Wook; Kim, Byung-Chul

    2012-04-06

    Highlights: Black-Right-Pointing-Pointer We examine the antiapoptotic mechanisms of Cdc25A. Black-Right-Pointing-Pointer Smad7 decreases the phosphorylation of I{kappa}B-alpha at Ser-32. Black-Right-Pointing-Pointer Smad7 positively regulates NF-{kappa}B activity through I{kappa}B-alpha ubiquitination. -- Abstract: Cell division cycle 25A (Cdc25A), a dual specificity protein phosphatase, exhibits anti-apoptotic activity, but the underlying molecular mechanisms are poorly characterized. Here we report that Cdc25A inhibits cisplatin-induced apoptotic cell death by stimulating nuclear factor-kappa B (NF-{kappa}B) activity. In HEK-293 cells, Cdc25A decreased protein level of inhibitor subunit kappa B alpha (I{kappa}-B{alpha}) in association with increased serine 32-phosphorylation, followed by stimulation of transcriptional activity of NF-{kappa}B. Inhibition of NF-{kappa}B activity by chemical inhibitor or overexpression of I{kappa}-B{alpha} in Cdc25A-elevated cancer cells resistant to cisplatin improved their sensitivity to cisplatin-induced apoptosis. Our data show for the first time that Cdc25A has an important physiological role in NF-{kappa}B activity regulation and it may be an important survival mechanism of cancer cells.

  18. Mustard NPR1, a mammalian I{kappa}B homologue inhibits NF-{kappa}B activation in human GBM cell lines

    SciTech Connect

    Kesanakurti, Divya; Sareddy, Gangadhara Reddy; Babu, Phanithi Prakash; Kirti, Pulugurtha Bharadwaja

    2009-12-18

    NF-{kappa}B activity is tightly regulated by I{kappa}B class of proteins. I{kappa}B proteins possess ankyrin repeats for binding to and inhibiting NF-{kappa}B. The regulatory protein, NPR1 from Brassica juncea possesses ankyrin repeats with sequence similarity to I{kappa}B{alpha} subgroup. Therefore, we examined whether stably expressed BjNPR1 could function as I{kappa}B in inhibiting NF-{kappa}B in human glioblastoma cell lines. We observed that BjNPR1 bound to NF-{kappa}B and inhibited its nuclear translocation. Further, BjNPR1 expression down-regulated the NF-{kappa}B target genes iNOS, Cox-2, c-Myc and cyclin D1 and reduced the proliferation rate of U373 cells. Finally, BjNPR1 decreased the levels of pERK, pJNK and PKC{alpha} and increased the Caspase-3 and Caspase-8 activities. These results suggested that inhibition of NF-{kappa}B activation by BjNPR1 can be a promising therapy in NF-{kappa}B dependent pathologies.

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

    SciTech Connect

    Chai, Xin-Sheng; Zhu, Jun Yong

    2002-01-01

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

  20. The general dielectric tensor for bi-kappa magnetized plasmas

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

    In this paper, we derive the dielectric tensor for a plasma containing particles described by an anisotropic superthermal (bi-kappa) velocity distribution function. The tensor components are written in terms of the two-variables kappa plasma special functions, recently defined by Gaelzer and Ziebell [Phys. Plasmas 23, 022110 (2016)]. We also obtain various new mathematical properties for these functions, which are useful for the analytical treatment, numerical implementation, and evaluation of the functions and, consequently, of the dielectric tensor. The formalism developed here and in the previous paper provides a mathematical framework for the study of electromagnetic waves propagating at arbitrary angles and polarizations in a superthermal plasma.

  1. Agreement, Shells, and Focus.

    ERIC Educational Resources Information Center

    Simpson, Andrew; Wu, Zoe

    2002-01-01

    Reconsiders development and licensing of agreement as a syntactic projection and argues for a productive developmental relation between agreement and the category of focus. Suggests that focus projections are initially selected by a variety of functional heads with real semantic content, then, over time decays into a simple concord shell. Upon…

  2. Non-Proliferation Agreements.

    ERIC Educational Resources Information Center

    Swalec, John J.

    1981-01-01

    Discusses five kinds of cooperative agreements established by the College of Lake County (IL): those with other community colleges/technical institutes; the military; business, industry, and organizations; secondary schools; and community and special interest groups. Pays particular attention to two kinds of agreements with other colleges. (CAM)

  3. Cooperative Agreements Study Report.

    ERIC Educational Resources Information Center

    Lawton, R. E.; Magruder, D.

    During the 1983 meeting of the Florida Legislature, action was taken to begin a systematic study of the level of cooperation between the Florida public schools K-12 program and the community and junior colleges. The goals and objectives of the Cooperative Agreements Study were to review and compile a list of the cooperative agreements and identify…

  4. The Helsinki Agreement

    ERIC Educational Resources Information Center

    Babel: Journal of the Australian Federation of Modern Language Teachers' Associations, 1977

    1977-01-01

    A reprint of sections of the Helsinki agreement dealing with foreign languages and civilization, and cooperation and exchanges in the field of education. The agreement supports wider knowledge of foreign languages and promotes exchanges, cooperation, lexicography, and specialized programs in adult education. (AMH)

  5. Receptor activator of nuclear factor kappa B ligand and osteoprotegerin levels in gingival crevicular fluid

    PubMed Central

    Sarlati, Fatemeh; Sattari, Mandana; Razzaghi, Shilan; Nasiri, Malihe

    2012-01-01

    Background: Osteoclastogenesis is coordinated by the interaction of three members of the tumor necrosis factor (TNF) superfamily: Osteoprotegerin (OPG)/receptor activator of nuclear factor kappa B ligand (RANKL)/receptor activator of nuclear factor kappa B (RANK). The aim of this study was to investigate RANKL and OPG levels, and their relative ratio in gingival crevicular fluid (GCF) of patients with chronic and aggressive periodontitis, as well as healthy controls. Materials and Methods: In this analytical study, GCF was obtained from healthy (n = 10), mild chronic periodontitis (n = 18), moderate chronic periodontitis (n = 18), severe chronic periodontitis (n = 20), and generalized aggressive periodontitis (n = 20) subjects. RANKL and OPG concentrations were measured by enzyme-linked immunosorbent assay. Statistical tests used were Kruskal–Wallis test, Mann–Whitney U rank sum test, and Spearman's rank correlation analysis. The level of statistical significance was set at P < 0.05. Results: Mean RANKL concentration showed no statistically significant differences between groups (P = 0.58). There were also no significant differences between mean OPG concentration in the five groups (P = 0.0.56). Moreover, relative RANKL/OPG ratio did not reveal a significant difference between the three study group subjects: healthy, chronic periodontitis (mild, moderate, severe), and aggressive periodontitis (P = 0.41). There was statistically significant correlation between the concentration of sRANKL and Clinical Attachment Level (CAL) in moderate chronic periodontitis patients (R = 0.48, P = 0.04). There was also negative correlation between OPG concentration and CAL in moderate chronic periodontitis patients, although not significant (R = −0.13). Conclusion: RANKL was prominent in periodontitis sites, especially in moderate periodontitis patients, whereas OPG was not detectable in some diseased sites with bleeding on probing, supporting the role of these two molecules in

  6. A novel small-molecule inhibitor of NF-{kappa}B signaling

    SciTech Connect

    Nakajima, Hiroto; Fujiwara, Hideyasu; Furuichi, Yasuhiro Tanaka, Keiji Shimbara, Naoki

    2008-04-18

    The inducible transcription factor NF-{kappa}B regulates divergent signaling pathways including inflammatory response and cancer development. Selective inhibitors for NF-{kappa}B signaling are potentially useful for treatment of inflammation and cancer. NF-{kappa}B is canonically activated by preferential disposal of its inhibitory protein; I{kappa}B, which suppresses the nuclear translocation of NF-{kappa}B. I{kappa}B{alpha} (a major member of I{kappa}B family proteins) is phosphorylated with an I{kappa}B kinase (IKK) and subsequently polyubiquitylated by SCF{sup {beta}}{sup TrCP1} ubiquitin-ligase in the presence of E1 and E2 prior to proteasomal degradation. Here, we describe a novel inhibitor termed GS143, which suppressed I{kappa}B{alpha} ubiquitylation, but not I{kappa}B{alpha} phosphorylation, MDM2-directed p53 ubiquitylation, and proteasome activity in vitro. GS143 markedly suppressed the destruction of I{kappa}B{alpha} stimulated by TNF{alpha} and a set of downstream responses coupled to NF-{kappa}B signaling but not those of p53 and {beta}-catenin in vivo. Our results indicate that GS143 serves as an effective inhibitor of multiple pathways served by NF-{kappa}B signaling.

  7. Retroperitoneal Sarcoma (RPS) High Risk Gross Tumor Volume Boost (HR GTV Boost) Contour Delineation Agreement Among NRG Sarcoma Radiation and Surgical Oncologists

    PubMed Central

    Baldini, Elizabeth H.; Bosch, Walter; Kane, John M.; Abrams, Ross A.; Salerno, Kilian E.; Deville, Curtiland; Raut, Chandrajit P.; Petersen, Ivy A.; Chen, Yen-Lin; Mullen, John T.; Millikan, Keith W.; Karakousis, Giorgos; Kendrick, Michael L.; DeLaney, Thomas F.; Wang, Dian

    2015-01-01

    Purpose Curative intent management of retroperitoneal sarcoma (RPS) requires gross total resection. Preoperative radiotherapy (RT) often is used as an adjuvant to surgery, but recurrence rates remain high. To enhance RT efficacy with acceptable tolerance, there is interest in delivering “boost doses” of RT to high-risk areas of gross tumor volume (HR GTV) judged to be at risk for positive resection margins. We sought to evaluate variability in HR GTV boost target volume delineation among collaborating sarcoma radiation and surgical oncologist teams. Methods Radiation planning CT scans for three cases of RPS were distributed to seven paired radiation and surgical oncologist teams at six institutions. Teams contoured HR GTV boost volumes for each case. Analysis of contour agreement was performed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics. Results HRGTV boost volume contour agreement between the seven teams was “substantial” or “moderate” for all cases. Agreement was best on the torso wall posteriorly (abutting posterior chest abdominal wall) and medially (abutting ipsilateral para-vertebral space and great vessels). Contours varied more significantly abutting visceral organs due to differing surgical opinions regarding planned partial organ resection. Conclusions Agreement of RPS HRGTV boost volumes between sarcoma radiation and surgical oncologist teams was substantial to moderate. Differences were most striking in regions abutting visceral organs, highlighting the importance of collaboration between the radiation and surgical oncologist for “individualized” target delineation on the basis of areas deemed at risk and planned resection. PMID:26018727

  8. A Population-Based Assessment of the Agreement Between Grading of Goniophotographic Images and Gonioscopy in the Chinese-American Eye Study (CHES)

    PubMed Central

    Murakami, Yohko; Wang, Dandan; Burkemper, Bruce; Lin, Shan C.; Varma, Rohit

    2016-01-01

    Purpose To compare grading of goniophotographic images and gonioscopy in assessing the iridocorneal angle. Methods In a population-based, cross-sectional study, participants underwent gonioscopy and goniophotographic imaging during the same visit. The iridocorneal angle was classified as closed if the posterior trabecular meshwork could not be seen. A single masked observer graded the goniophotographic images, and each eye was classified as having angle closure based on the number of closed quadrants. Agreement between the methods was analyzed by calculating kappa (κ) and first-order agreement coefficient (AC1) statistics and comparison of area under receiver operating characteristic curves (AUC). Results A total of 4149 Chinese Americans (3994 eyes) were included in this study. The agreement for angle closure diagnosis between gonioscopy and EyeCam was moderate to excellent (κ = 0.60, AC1 0.90, AUC 0.76–0.80). Conclusions Detection of iridocorneal angle closure based on goniophotographic imaging shows moderate to very good agreement with angle closure assessment using gonioscopy. PMID:27571018

  9. Analysis of agreement between cardiac risk stratification protocols applied to participants of a center for cardiac rehabilitation

    PubMed Central

    Santos, Ana A. S.; Silva, Anne K. F.; Vanderlei, Franciele M.; Christofaro, Diego G. D.; Gonçalves, Aline F. L.; Vanderlei, Luiz C. M.

    2016-01-01

    ABSTRACT Background Cardiac risk stratification is related to the risk of the occurrence of events induced by exercise. Despite the existence of several protocols to calculate risk stratification, studies indicating that there is similarity between these protocols are still unknown. Objective To evaluate the agreement between the existing protocols on cardiac risk rating in cardiac patients. Method The records of 50 patients from a cardiac rehabilitation program were analyzed, from which the following information was extracted: age, sex, weight, height, clinical diagnosis, medical history, risk factors, associated diseases, and the results from the most recent laboratory and complementary tests performed. This information was used for risk stratification of the patients in the protocols of the American College of Sports Medicine, the Brazilian Society of Cardiology, the American Heart Association, the protocol designed by Frederic J. Pashkow, the American Association of Cardiovascular and Pulmonary Rehabilitation, the Société Française de Cardiologie, and the Sociedad Española de Cardiología. Descriptive statistics were used to characterize the sample and the analysis of agreement between the protocols was calculated using the Kappa coefficient. Differences were considered with a significance level of 5%. Results Of the 21 analyses of agreement, 12 were considered significant between the protocols used for risk classification, with nine classified as moderate and three as low. No agreements were classified as excellent. Different proportions were observed in each risk category, with significant differences between the protocols for all risk categories. Conclusion The agreements between the protocols were considered low and moderate and the risk proportions differed between protocols. PMID:27556385

  10. Accuracy of grading of urothelial carcinoma on urine cytology: an analysis of interobserver and intraobserver agreement

    PubMed Central

    Reid, Michelle D; Osunkoya, Adeboye O; Siddiqui, Momin T; Looney, Stephen W

    2012-01-01

    Background: Urine samples of known urothelial carcinoma were independently graded by 3 pathologists with (MS, MR) and without (AO) fellowship training in cytopathology using a modified version of the 2004 2-tiered World Health Organization classification system. By measuring interobserver and intraobserver agreement among pathologists, compared with the gold standard of biopsy/resection, specimen accuracy and reproducibility of grading in urine was determined. Methods: 44 urine cytology samples were graded as low or high-grade by 3 pathologists with a 2-3 week interval between grading. Pathologists were blinded to their and others’ grades and histologic diagnoses. Coefficient kappa was used to measure interobserver and intraobserver agreement among pathologists. Accuracy was measured by percentage agreement with the biopsy/resection separately for each pathologist, and for all pathologists and occasions combined. Results: The overall accuracy was 77% (95% C.I., 72% - 82%). Pathologist AO was significantly more accurate than MR on occasion 1 (p = 0.006) and 2 (p = 0.039). No other significant differences were found among the observers. Interobserver agreement using coefficient kappa was unacceptably low, with all but one of the kappa value being less than 0.40, the cutoff for a “fair” degree of agreement. Intraobserver agreement, as measured by coefficient kappa, was adequate. Conclusions: Our study underscores the lack of precision and subjective nature of grading urothelial carcinoma on urine samples. There was poor inter- and intraobserver agreement among pathologists despite fellowship training in cytopathology. Clinicians and cytopathologists should be mindful of this pitfall and avoid grading urothelial carcinoma on urine samples, especially since grading may impact patient management. PMID:23119105

  11. Characterization of human kappa-casein purified by FPLC.

    PubMed

    Dev, B C; Sood, S M; DeWind, S; Slattery, C W

    1993-08-01

    Because previous purification procedures for human kappa-casein may have caused the loss of some carbohydrate, relatively gentle methods were used. The protein was isolated by a four-step procedure which included isoelectric precipitation of whole casein, gel chromatography on Sephadex G-200 in the presence of SDS, removal of the SDS with Extracti-Gel D, and FPLC chromatography on Mono Q with buffers containing 6 M urea. The purified protein was nearly identical in amino acid composition to that found earlier by amino acid analysis and peptide sequencing and a molar extinction coefficient of 11.2 +/- 0.1 was determined on the basis of amino acid analysis with a norleucine internal standard. Hydrolysis, acylation, and methylsilylation of the carbohydrate, followed by gas chromatographic analysis on a fused silica column, yielded approximately 5% fucose, 17% galactose, 18% N-acetylglucosamine, 8% N-acetylgalactosamine and 7% sialic acid, totaling almost 55% by weight. The percentages from two different donors were almost the same. About 1 mole phosphorus per mole of kappa-casein was also detected. Using low-speed sedimentation equilibrium methods, a molecular weight of only 33,400 was obtained for human kappa-casein, suggesting carbohydrate lability. Human beta-casein with four phosphoryls was stabilized against precipitation by 10 mM Ca+2 ions at a level greater than 95% when the molar ratio of kappa/beta exceeded 0.15. PMID:8361956

  12. Kappa opioid receptors stimulate phosphoinositide turnover in rat brain

    SciTech Connect

    Periyasamy, S.; Hoss, W. )

    1990-01-01

    The effects of various subtype-selective opioid agonists and antagonists on the phosphoinositide (PI) turnover response were investigated in the rat brain. The {kappa}-agonists U-50,488H and ketocyclazocine produced a concentration-dependent increase in the accumulation of IP's in hippocampal slices. The other {kappa}-agonists Dynorphin-A (1-13) amide, and its protected analog D(Ala){sup 2}-dynorphin-A (1-13) amide also produced a significant increase in the formation of ({sup 3}H)-IP's, whereas the {mu}-selective agonists (D-Ala{sup 2}-N-Me-Phe{sup 4}-Gly{sup 5}-ol)-enkephalin and morphine and the {delta}-selective agonist (D-Pen{sup 2,5})-enkephalin were ineffective. The increase in IP's formation elicited by U-50,488H was partially antagonized by naloxone and more completely antagonized by the {kappa}-selective antagonists nor-binaltorphimine and MR 2266. The formation of IP's induced by U-50,488H varies with the regions of the brain used, being highest in hippocampus and amygdala, and lowest in striatum and pons-medullar. The results indicate that brain {kappa}- but neither {mu}- nor {delta}- receptors are coupled to the PI turnover response.

  13. Scalar field theory in {kappa}-Minkowski spacetime from twist

    SciTech Connect

    Kim, Hyeong-Chan; Lee, Youngone; Rim, Chaiho; Yee, Jae Hyung

    2009-10-15

    Using the twist deformation of U(igl(4,R)), the linear part of the diffeomorphism, we define a scalar function and construct a free scalar field theory in four-dimensional {kappa}-Minkowski spacetime. The action in momentum space turns out to differ only in the integration measure from the commutative theory.

  14. 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.

  15. Agreement between cranial and facial classification through clinical observation and anthropometric measurement among envigado school children

    PubMed Central

    2014-01-01

    Background To evaluate the agreement between cranial and facial classification obtained by clinical observation and anthropometric measurements among school children from the municipality of Envigado, Colombia. Methods This cross-sectional study was carried out among 8-15-year-old children. Initially, an indirect clinical observation was made to determine the skull pattern (dolichocephalic, mesocephalic or brachycephalic), based on visual equivalence of right eurion- left eurion and glabella-opisthocranion anthropometric points, as well as the facial type (leptoprosopic, mesoprosopic and euryprosopic), according to the left and right zygomatic, nasion and gnation points. Following, a direct measurement was conducted with an anthropometer using the same landmarks for cranial width and length, as well as for facial width and height. Subsequently, both the facial index [euryprosopic (≤80.9%), mesoprosopic (between 81% - 93%) and leptoprosopic (≥93.1%)] and the cranial index [dolichocephalic (index ≤ 75.9%), mesocephalic (between 76% - 81%), and brachycephalic (≥81.1%)] were determined. Concordance between the indices obtained was calculated by direct and indirect measurement using the Kappa statistic. Results A total of 313 students were enrolled; 172 (55%) were female and 141 (45%) male. The agreement between the direct and indirect facial index measurements was 0.189 (95% CI 0.117-0261), and the cranial index was 0.388 (95% CI 0.304-0.473), indicating poor concordance. Conclusions No agreement was observed between direct measurements conducted with an anthropometer and indirect measurements via visual evaluation. Therefore, the indirect visual classification method is not appropriate to calculate the cranial and facial indices. PMID:24886038

  16. Importance of Kappa Background Electron Distributions to Solar Radio Bursts

    NASA Astrophysics Data System (ADS)

    Cairns, I. H.; Schmidt, J. M.; Li, B.

    2015-12-01

    The Sun produces intense radio emissions by collective processes and by incoherent single-particle processes, both of which depend sensitively on the electron distribution function present. Examples of the former include metric type II and III bursts produced by the so-called plasma emission processes, while examples of the latter include decametric and metric continua produced by the bremstrahlung and gyrosynchrotron processes. Kappa electron distributions, which appear power-law at high energies, qualitatively alter the spectral shape for the incoherent processes and increase the total flux (due to the increased number of high energy electrons). Kappa distributions are also vital for collective processes, due to the increased number of fast electrons (and so energy available) again and also due to the greatly ncreased level of the nonthermal background distribution onto which is superposed the distribution function of fast particles responsible for the collectively-produced waves and radio emissions. Two examples are presented, one for each reason. For type II bursts the level and frequency-time structures (above background) of predicted radio emission change qualitatively when kappa rather than Maxwellian background electrons are assumed, due to the increased numbers of fast electrons reflected by the type II shock. While this effect is also important for type III bursts produced by fast electron beams, our simulations show that the crucial qualitative change is that beam speeds above 0.3 c only develop in the simulations when kappa background electrons are present, due to the high level of the kappa tail preventing quasilinear relaxation of the beam electrons to smaller speeds.

  17. Endogenous Depression in the Elderly: Prevalence and Agreement among Measures.

    ERIC Educational Resources Information Center

    Gallagher-Thompson, Dolores; And Others

    1992-01-01

    Examined agreement among diagnoses made according to 5 definitions of endogenous depression in 99 depressed elders. Poor to fair agreement was generally demonstrated, except for Research Diagnostic Criteria and Diagnostic and Statistical Manual of Mental Disorders, which demonstrated excellent agreement. Mostly, demographic and clinical variables…

  18. Cosmic statistics of statistics

    NASA Astrophysics Data System (ADS)

    Szapudi, István; Colombi, Stéphane; Bernardeau, Francis

    1999-12-01

    The errors on statistics measured in finite galaxy catalogues are exhaustively investigated. The theory of errors on factorial moments by Szapudi & Colombi is applied to cumulants via a series expansion method. All results are subsequently extended to the weakly non-linear regime. Together with previous investigations this yields an analytic theory of the errors for moments and connected moments of counts in cells from highly non-linear to weakly non-linear scales. For non-linear functions of unbiased estimators, such as the cumulants, the phenomenon of cosmic bias is identified and computed. Since it is subdued by the cosmic errors in the range of applicability of the theory, correction for it is inconsequential. In addition, the method of Colombi, Szapudi & Szalay concerning sampling effects is generalized, adapting the theory for inhomogeneous galaxy catalogues. While previous work focused on the variance only, the present article calculates the cross-correlations between moments and connected moments as well for a statistically complete description. The final analytic formulae representing the full theory are explicit but somewhat complicated. Therefore we have made available a fortran program capable of calculating the described quantities numerically (for further details e-mail SC at colombi@iap.fr). An important special case is the evaluation of the errors on the two-point correlation function, for which this should be more accurate than any method put forward previously. This tool will be immensely useful in the future for assessing the precision of measurements from existing catalogues, as well as aiding the design of new galaxy surveys. To illustrate the applicability of the results and to explore the numerical aspects of the theory qualitatively and quantitatively, the errors and cross-correlations are predicted under a wide range of assumptions for the future Sloan Digital Sky Survey. The principal results concerning the cumulants ξ, Q3 and Q4 is that

  19. 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.

  20. Kappa Fornaci, A Triple Radio Star

    NASA Astrophysics Data System (ADS)

    Tokovinin, Andrei

    2013-03-01

    Bright and nearby (22 pc) solar-type dwarf κ For (HIP 11072) is a triple system. The close pair of M-type dwarfs Ba,Bb with a tentative period of 3.7 days moves around the main component A on a 26 yr orbit. The mass of the "dark companion" Ba+Bb is comparable to the mass of A, causing large motion of the photo-center. The combined spectro-interferometric orbit of AB is derived, and the relative photometry of the components A and B is given. A weak signature of Ba and Bb is detected in the high-resolution spectra by cross-correlation and by variable emission in the Balmer hydrogen lines. The activity of the M dwarfs, manifested by a previously detected radio flare, is likely maintained by synchronization with their tight orbit. We discuss the frequency of similar hidden triple systems, methods of their detection, and the implications for multiple-star statistics. Based on observations obtained with CHIRON spectrometer at the 1.5 m CTIO telescope operated by SMARTS (NOAO program 2012B-0075), at the SOAR telescope, and at the Gemini Observatory (program GS-2012B-Q-71, PI: M. Hartung).

  1. Agreement in cardiovascular risk rating based on anthropometric parameters

    PubMed Central

    Dantas, Endilly Maria da Silva; Pinto, Cristiane Jordânia; Freitas, Rodrigo Pegado de Abreu; de Medeiros, Anna Cecília Queiroz

    2015-01-01

    Objective To investigate the agreement in evaluation of risk of developing cardiovascular diseases based on anthropometric parameters in young adults. Methods The study included 406 students, measuring weight, height, and waist and neck circumferences. Waist-to-height ratio and the conicity index. The kappa coefficient was used to assess agreement in risk classification for cardiovascular diseases. The positive and negative specific agreement values were calculated as well. The Pearson chi-square (χ2) test was used to assess associations between categorical variables (p<0.05). Results The majority of the parameters assessed (44%) showed slight (k=0.21 to 0.40) and/or poor agreement (k<0.20), with low values of negative specific agreement. The best agreement was observed between waist circumference and waist-to-height ratio both for the general population (k=0.88) and between sexes (k=0.93 to 0.86). There was a significant association (p<0.001) between the risk of cardiovascular diseases and females when using waist circumference and conicity index, and with males when using neck circumference. This resulted in a wide variation in the prevalence of cardiovascular disease risk (5.5%-36.5%), depending on the parameter and the sex that was assessed. Conclusion The results indicate variability in agreement in assessing risk for cardiovascular diseases, based on anthropometric parameters, and which also seems to be influenced by sex. Further studies in the Brazilian population are required to better understand this issue. PMID:26466060

  2. Activation of NF-kappa B in vivo is regulated by multiple phosphorylations.

    PubMed Central

    Naumann, M; Scheidereit, C

    1994-01-01

    The activation of nuclear factor kappa B (NF-kappa B) in intact cells is mechanistically not well understood. Therefore we investigated the modifications imposed on NF-kappa B/I kappa B components following stimulation and show that the final step of NF-kappa B induction in vivo involves phosphorylation of several members of the NF-kappa B/I kappa B protein families. In HeLa cells as well as in B cells, TNF-alpha rapidly induced nuclear translocation primarily of p50-p65, but not of c-rel. Both NF-kappa B precursors and I kappa B alpha became strongly phosphorylated with the same kinetics. In addition to the inducible phosphorylation after stimulation, B lymphocytes containing constitutive nuclear NF-kappa B revealed constitutively phosphorylated p65 and I kappa B alpha. Phosphorylation was accompanied by induced processing of the precursors p100 and p105 and by degradation of I kappa B alpha. As an in vitro model we show that phosphorylation of p105 impedes its ability to interact with NF-kappa B, as has been shown before for I kappa B alpha. Surprisingly, even p65, but not c-rel, was phosphorylated after induction in vivo, suggesting that TNF-alpha selectively activates only specific NF-kappa B heteromers and that modifications regulate not only I kappa B molecules but also NF-kappa B molecules. In fact, cellular NF-kappa B activity was phosphorylation-dependent and the DNA binding activity of p65-containing NF-kappa B was enhanced by phosphorylation in vitro. Furthermore, we found that the induction by hydrogen peroxide of NF-kappa B translocation to the nucleus, which is assumed to be triggered by reactive oxygen intermediates, also coincided with incorporation of phosphate into the same subunits that were modified after stimulation by TNF-alpha. Thus, phosphorylation appears to be a general mechanism for activation of NF-kappa B in vivo. Images PMID:7925300

  3. FFTF Authorization Agreement

    SciTech Connect

    DAUTEL, W.A.

    2000-09-25

    The purpose of the Authorization Agreement is to serve as a mechanism whereby the U.S. Department of Energy, Richland Operations Office (RL) and Fluor Hanford (FH) jointly clarify and agree to key conditions for conducting work safely and efficiently in the Fast Flux Test Facility (FFTF). Work must be accomplished in a manner that achieves high levels of quality while protecting the environment and the safety and health of workers and the public, and complying with applicable contractual and regulatory requirements. It is the intent of this Agreement to address those items of significant importance in establishing and supporting the FFTF Authorization Envelope, but this Agreement in no way alters the terms and conditions of the Project Hanford Management Contract (PHMC), Contract Number DE-AC06-96RL13200.

  4. MEASURING NEBULAR TEMPERATURES: THE EFFECT OF NEW COLLISION STRENGTHS WITH EQUILIBRIUM AND {kappa}-DISTRIBUTED ELECTRON ENERGIES

    SciTech Connect

    Nicholls, David C.; Dopita, Michael A.; Sutherland, Ralph S.; Kewley, Lisa J.; Palay, Ethan

    2013-08-15

    In this paper we develop tools for observers to use when analyzing nebular spectra for temperatures and metallicities, with two goals: to present a new, simple method to calculate equilibrium electron temperatures for collisionally excited line flux ratios, using the latest atomic data; and to adapt current methods to include the effects of possible non-equilibrium ''{kappa}'' electron energy distributions. Adopting recent collision strength data for [O III], [S III], [O II], [S II], and [N II], we find that existing methods based on older atomic data seriously overestimate the electron temperatures, even when considering purely Maxwellian statistics. If {kappa} distributions exist in H II regions and planetary nebulae as they do in solar system plasmas, it is important to investigate the observational consequences. This paper continues our previous work on the {kappa} distribution. We present simple formulaic methods that allow observers to (1) measure equilibrium electron temperatures and atomic abundances using the latest atomic data, and (2) to apply simple corrections to existing equilibrium analysis techniques to allow for possible non-equilibrium effects. These tools should lead to better consistency in temperature and abundance measurements, and a clearer understanding of the physics of H II regions and planetary nebulae.

  5. Obliquely propagating electrostatic waves in a magnetized plasma for different types of anisotropic kappa distribution

    NASA Astrophysics Data System (ADS)

    Bashir, M. F.; Yoon, P. H.; Murtaza, G.; Aqeel, D.; Javed, S.; Zahra, M.

    2015-12-01

    By using the kinetic theory, the dispersion relation of obliquely propagating electrostatic waves are discussed for three types of kappa distribution function: 1) loss-cone-bi-kappa-Maxwellian distribution, 2) current carrying Bi-kappa-Maxwellian distribution and 3) product-bi-kappa distribution. The effects of kappa-index, loss-cone index, streaming velocity and the temperature anisotropy on the Harris instability is highlighted for their possible application to explain the banded emissions observed in the terrestrial magnetosphere and in the magnetospheres of other planets, e.g., Jupiter, Saturn, Uranus, and in Io's plasma torus.

  6. Radio Emissions from Plasma with Electron Kappa-Distributions

    NASA Astrophysics Data System (ADS)

    Fleishman, G. D.; Kuznetsov, A. A.

    2015-12-01

    Gregory Fleishman (New Jersey Institute of Technology, Newark, USA)Alexey Kuznetsov (Institute of Solar-Terrestrial Physics, Irkutsk, Russia), Currently there is a concern about the ability of the classical thermal (Maxwellian) distribution to describe quasisteady-state plasma in the solar atmosphere, including active regions. In particular, other distributions have been proposed to better fit observations, for example, kappa-distributions. If present, these distributions will generate radio emissions with different observable properties compared with the classical gyroresonance (GR) or free-free emission, which implies a way of remotely detecting these kappa distributions in the radio observations. Here we present analytically derived GR and free-free emissivities and absorption coefficients for the kappa-distribution, and discuss their properties, which are in fact remarkably different from the classical Maxwellian plasma. In particular, the radio brightness temperature from a gyrolayer increases with the optical depth τ for kappa-distribution. This property has a remarkable consequence allowing a straightforward observational test: the GR radio emission from the non-Maxwellian distributions is supposed to be noticeably polarized even in the optically thick case, where the emission would have strictly zero polarization in the case of Maxwellian plasma. This offers a way of remote probing the plasma distribution in astrophysical sources, including solar active regions as a vivid example. In this report, we present analytical formulae and computer codes to calculate the emission parameters. We simulate the gyroresonance emission under the conditions typical of the solar active regions and compare the results for different electron distributions. We discuss the implications of our findings for interpretation of radio observations. This work was supported in part by NSF grants AGS-1250374 and AGS-1262772, NASA grant NNX14AC87G to New Jersey Institute of Technology

  7. The involvement of an LPS inducible I kappa B kinase in endotoxin tolerance.

    PubMed

    Kohler, N G; Joly, A

    1997-03-27

    When human ovarian carcinoma cells are challenged with endotoxin, an I kappa B kinase is transiently induced within 3 to 5 min. This enzyme activity causes the hyperphosphorylation and subsequent degradation of I kappa B which allows NF-kappa B to translocate to the nucleus where it activates transcription. When endotoxin treated cells are rechallenged with a second dose of LPS, I kappa B kinase is not detected and I kappa B remains in the cytoplasm where it sequesters NF-kappa B. We report here the absence of endotoxin inducible I kappa B kinase activity in endotoxin tolerant cells suggesting that I kappa B kinase may play an important role in endotoxin tolerance. When cells tolerant to endotoxin are treated with TNF, I kappa B kinase activity is induced. Thus cells that are endotoxin tolerant are not cross tolerant to TNF. Dexamethasone, a known inhibitor of NF-kappa B activation does not inhibit endotoxin dependent induction of I kappa B kinase suggesting that the mechanism of action of dexamethasone is different from the tolerance mechanism reported here.

  8. Synaptic localization of. kappa. opioid receptors in guinea pig neostriatum

    SciTech Connect

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

    1992-01-15

    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 dendrodendritic 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.

  9. Kappa casein gene polymorphism in local Tunisian goats.

    PubMed

    Jemmali, B; Ben Gara, A; Selmi, H; Ammari, Z; Bouheni, C; Ben Larbi, M; Hammami, M; Amraoui, M; Kamoun, M; Rouissi, H; Rekik, B

    2013-12-15

    The genetic polymorphism of the goat Kappa casein was investigated in Tunisian goats. Blood samples were collected from local goat breeds. Samples of genomic DNA were obtained from leukocytes of 175 dairy goats and regions of interest in the gene were amplified by Polymerase Chain Reaction (PCR) and then evaluated in agarose gel. For a better characterization of the single nucleotide polymorphism, a PCR-Restriction Fragment Length Polymorphism was performed employing the endonuclease DNA amplification using 459 bp primers. The PCR products of primers (459 bp) digested by restriction enzyme Alw44I produced two fragments of 459 and 381 bp. The Kappa casein allelic variants in tested animals revealed different genotypes, two of them were homozygous: AA or BB, AC or BC and CC. Genotypic frequencies were 12.5, 60.5 and 27% for AA or BB, CC and AC or BC, respectively. Identification of different variants of the Kappa casein can be used for the improvement and conservation of Tunisian local goats.

  10. Experimental autoimmune encephalomyelitis: Association with mutual regulation of RelA (p65)/NF-{kappa}B and phospho-I{kappa}B in the CNS

    SciTech Connect

    Hwang, Insun; Ha, Danbee; Ahn, Ginnae; Park, Eunjin; Joo, Haejin; Jee, Youngheun

    2011-07-29

    Highlights: {yields} The phosphorylation of RelA's inhibitory factor I{kappa}B and subsequent RelA activation are important to the disease process of EAE. {yields} The expression of RelA and phospho-I{kappa}B was markedly increased in the initiation and during the progression of EAE. {yields} TPCK-treated EAE mice showed lower incidence of EAE with less severe symptoms and quicker recovery than vehicle-treated EAE mice. {yields} TPCK significantly suppressed the MOG{sub 35-55}-specific T cell proliferation by reducing the production of IFN-{gamma} and IL-17 cytokines in EAE. {yields} The NF-{kappa}B cascade's activity increased gradually with the development of symptoms and brain pathology of EAE. -- Abstract: Recently emerging evidence that the NF-{kappa}B family plays an important role in autoimmune disease has produced very broad and sometimes paradoxical conclusions. In the present study, we elucidated that the activation of RelA (p65) of NF-{kappa}B and I{kappa}B dissociation assumes a distinct role in experimental autoimmune encephalomyelitis (EAE) progression by altering I{kappa}B phosphorylation and/or degradation. In the present study of factors that govern EAE, the presence and immunoreactivity of nuclear RelA and phospho-I{kappa}B were recorded at the initiation and peak stage, and degradation of I{kappa}B{alpha} progressed rapidly at an early stage then stabilized during recovery. The immunoreactivity to RelA and phospho-I{kappa}B occurred mainly in inflammatory cells and microglial cells but only slightly in astrocytes. Subsequently, the blockade of I{kappa}B dissociation from NF-{kappa}B reduced the severity of disease by decreasing antigen-specific T cell response and production of IL-17 in EAE. Thus, blocking the dissociation of I{kappa}B from NF-{kappa}B can be utilized as a strategy to inhibit the NF-{kappa}B signal pathway thereby to reduce the initiation, progression, and severity of EAE.

  11. Characterization of the molecular events following impairment of NF-kappaB-driven transcription in neurons.

    PubMed

    Chiarugi, Alberto

    2002-12-30

    Nuclear factor-kappaB (NF-kappaB) is a transcription factor with a pivotal role in neuronal homeostasis. Indeed, NF-kappaB trans-activates several antiapoptotic genes in neurons and inhibition of NF-kappaB transcriptional activity triggers neuronal apoptosis. However, the exact mechanisms by which neurons undergo apoptosis in conditions of NF-kappaB inhibition are poorly understood. To further clarify how NF-kappaB operates in neurons, and to gather information on the molecular events occurring during NF-kappaB inhibition-dependent neuronal apoptosis, this study evaluated the effects of recently identified NF-kappaB inhibitors such as parthenolide, SN50, BAY 11-7082 and helenalin on primary cultures of rat cortical neurons. Data show that NF-kappaB was constitutively activated in neurons, and demonstrate for the first time that drug-dependent NF-kappaB inhibition induced rapid mitochondrial release of cytochrome c, caspase-9 and -3 activation, poly(ADP-ribose) polymerase-1 cleavage, membrane blebbing and nuclear fragmentation, without evidence of procaspase-8 and Bid processing. Interestingly, a burst of Akt activation occurred in neurons exposed to NF-kappaB inhibitors. These events were preceded by selective reduction of mRNAs of NF-kappaB-dependent, antiapoptotic Bcl-2 family members such as Bcl-x(L), Bcl-2 and, in particular, A1/Bfl-1. The present study reports a novel, detailed temporal analysis of the molecular events following impairment of NF-kappaB-driven transcription in neurons and demonstrates that inhibition of constitutive neuronal NF-kappaB activity triggers selective activation of the intrinsic apoptotic program.

  12. Treatment of kappa in Recent Western US Seismic Nuclear Plant Probabilistic Seismic Hazard Studies

    NASA Astrophysics Data System (ADS)

    Toro, G. R.; Di Alessandro, C.; Al Atik, L.

    2015-12-01

    The three operating nuclear plants (Diablo Canyon, Palo Verde, and Columbia Generating Station) in the western United States recently performed SSHAC Level 3 seismic hazard studies in response to a Request for Information by the Nuclear Regulatory Commission, following the accident at the Fukushima Dai-ichi nuclear facility. The treatment of zero-distance kappa, referred to as kappa_0 and commonly attributed to material damping and scattering in the shallow crust, was given extensive consideration in these studies. Available ground motion prediction equations (GMPEs) do not typically include kappa_0 as a prediction parameter and are developed for an average kappa_0 of the host region. Kappa scaling is routinely applied to adjust for the differences in average kappa between the GMPEs host regions and the target regions. The impact of kappa scaling on the results of probabilistic seismic hazard analyses is significant for nuclear and other facilities that are sensitive to high frequency ground motions (frequencies greater than about 10 Hz). There are several available approaches for deriving kappa scaling factors to GMPEs, which all require estimating kappa_0 at the target site. It is difficult to constrain the target kappa_0 empirically due to the scarcity of ground-motion data from hard-rock sites in ground-motion databases.The hazard studies for the three nuclear power plants had different data, faced different challenges in the estimation of kappa_0, and used different methods for the estimation of the effect of kappa_0 on the site-specific ground motions. This presentation summarizes the approaches used for the evaluation of kappa_0 and for their incorporation in the probabilistic seismic hazard analysis. Emphasis is given to the quantification of the kappa_0 uncertainty, and on the evaluation of its impact to the resulting seismic hazard at the different sites.

  13. Activation of NF-kappa B by reactive oxygen intermediates in the nervous system.

    PubMed

    Kaltschmidt, B; Sparna, T; Kaltschmidt, C

    1999-01-01

    Nuclear factor kappa B (NF-kappa B) is a transcription factor crucially involved in glial and neuronal function. NF-kappa B is ubiquitously distributed within the nervous system, and its inducible activity can be discerned from constitutive activity. Prototypic inducible NF-kappa B in the nervous system is composed of the DNA-binding subunits p50 and p65 complexed with an inhibitory I kappa B-alpha molecule. A number of signals from the cell surface can lead to rapid activation of NK-kappa B, thus releasing the inhibition by I kappa B. This activates translocation of NF-kappa B to the nucleus, where it binds to kappa B motifs of target genes and activates transcription. Previous findings have identified reactive oxygen intermediates (ROI) as a common denominator of NF-kappa B activating signals. More specifically, hydrogen peroxide (H2O2) might be used as second messenger in the NF-kappa B system, despite its cytotoxicity. Analysis of pathways leading to NF-kappa B activation in the nervous system has identified a number of ROI-dependent pathways such as cytokine- and neurotrophin-mediated activation, glutamatergic signal transduction, and various diseases with crucial ROI involvement (e.g., Alzheimer's disease, Parkinson's disease, experimental autoimmune encephalomyelitis, multiple sclerosis, amyotrophic lateral sclerosis, and injury). A number of NF-kappa B-specific target genes contribute to the production of ROI or are involved in detoxification of ROIs. In this review, possible mechanisms and regulatory pathways of ROI-mediated NF-kappa B activation are discussed.

  14. Evaluation of Spatial Agreement of Distinct Landslide Prediction Models

    NASA Astrophysics Data System (ADS)

    Sterlacchini, Simone; Bordogna, Gloria; Frigerio, Ivan

    2013-04-01

    The aim of the study was to assess the degree of spatial agreement of different predicted patterns in a majority of coherent landslide prediction maps with almost similar success and prediction rate curves. If two or more models have a similar performance, the choice of the best one is not a trivial operation and cannot be based on success and prediction rate curves only. In fact, it may happen that two or more prediction maps with similar accuracy and predictive power do not have the same degree of agreement in terms of spatial predicted patterns. The selected study area is the high Valtellina valley, in North of Italy, covering a surface of about 450 km2 where mapping of historical landslides is available. In order to assess landslide susceptibility, we applied the Weights of Evidence (WofE) modeling technique implemented by USGS by means of ARC-SDM tool. WofE efficiently investigate the spatial relationships among past events and multiple predisposing factors, providing useful information to identify the most probable location of future landslide occurrences. We have carried out 13 distinct experiments by changing the number of morphometric and geo-environmental explanatory variables in each experiment with the same training set and thus generating distinct models of landslide prediction, computing probability degrees of occurrence of landslides in each pixel. Expert knowledge and previous results from indirect statistically-based methods suggested slope, land use, and geology the best "driving controlling factors". The Success Rate Curve (SRC) was used to estimate how much the results of each model fit the occurrence of landslides used for the training of the models. The Prediction Rate Curve (PRC) was used to estimate how much the model predict the occurrence of landslides in the validation set. We found that the performances were very similar for different models. Also the dendrogram of the Cohen's kappa statistic and Principal Component Analysis (PCA) were

  15. 28 CFR 22.24 - Information transfer agreement.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... STATISTICAL INFORMATION § 22.24 Information transfer agreement. Prior to the transfer of any identifiable... identifiable to a private person will be used only for research and statistical purposes. (b) Information...-know basis for research or statistical purposes, provided that such transfer is approved by the...

  16. 28 CFR 22.24 - Information transfer agreement.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... STATISTICAL INFORMATION § 22.24 Information transfer agreement. Prior to the transfer of any identifiable... identifiable to a private person will be used only for research and statistical purposes. (b) Information...-know basis for research or statistical purposes, provided that such transfer is approved by the...

  17. 28 CFR 22.24 - Information transfer agreement.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... STATISTICAL INFORMATION § 22.24 Information transfer agreement. Prior to the transfer of any identifiable... identifiable to a private person will be used only for research and statistical purposes. (b) Information...-know basis for research or statistical purposes, provided that such transfer is approved by the...

  18. 28 CFR 22.24 - Information transfer agreement.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... STATISTICAL INFORMATION § 22.24 Information transfer agreement. Prior to the transfer of any identifiable... identifiable to a private person will be used only for research and statistical purposes. (b) Information...-know basis for research or statistical purposes, provided that such transfer is approved by the...

  19. 28 CFR 22.24 - Information transfer agreement.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... STATISTICAL INFORMATION § 22.24 Information transfer agreement. Prior to the transfer of any identifiable... identifiable to a private person will be used only for research and statistical purposes. (b) Information...-know basis for research or statistical purposes, provided that such transfer is approved by the...

  20. Agreements in Virtual Organizations

    NASA Astrophysics Data System (ADS)

    Pankowska, Malgorzata

    This chapter is an attempt to explain the important impact that contract theory delivers with respect to the concept of virtual organization. The author believes that not enough research has been conducted in order to transfer theoretical foundations for networking to the phenomena of virtual organizations and open autonomic computing environment to ensure the controllability and management of them. The main research problem of this chapter is to explain the significance of agreements for virtual organizations governance. The first part of this chapter comprises explanations of differences among virtual machines and virtual organizations for further descriptions of the significance of the first ones to the development of the second. Next, the virtual organization development tendencies are presented and problems of IT governance in highly distributed organizational environment are discussed. The last part of this chapter covers analysis of contracts and agreements management for governance in open computing environments.

  1. Countries renew rescue agreement

    NASA Astrophysics Data System (ADS)

    Bush, Susan M.

    To insure long-term continuity for the international satellite search and rescue system, COSPAS/SARSAT, an intergovernmental agreement binding the four sponsoring nations to cooperate was signed July 1 in Paris. According to Russell Vollmers of the National Oceanic and Atmospheric Administration, the agreement is binding for 15 years, with an automatic extension.The system marked the fifth anniversary of its first rescue last year, when on September 10, 1982, three persons were rescued. Begun in the 1970s by NASA as an experiment, COSPAS/SARSAT (a Russian-English acronym) is now a cooperative project among the United States, Canada, France, and the Soviet Union. Its goal is to reduce the time required to rescue air and maritime distress victims and also to locate victims who otherwise may not be found, thus using the satellite system as a life-saving device.

  2. Immunoglobulin G kappa [IgG kappa] and IgG lambda paraproteinemia in a child with AIDS and response to highly active antiretroviral therapy.

    PubMed

    Seeborg, Filiz Odabasi; Gay, Hannah; Schmiege, Lorenz M; Bernard, David; Shearer, William T

    2005-11-01

    We report an 8-year-old boy with AIDS, extremely elevated serum immunoglobulin G (IgG) concentration and IgG kappa [IgG(kappa)] and IgG lambda [IgG(lambda)] paraproteinemia. This paraproteinemia partially responded to highly active antiretroviral therapy. This case emphasizes the importance of controlling B-cell activation. PMID:16275950

  3. Statistics 101 for Radiologists.

    PubMed

    Anvari, Arash; Halpern, Elkan F; Samir, Anthony E

    2015-10-01

    Diagnostic tests have wide clinical applications, including screening, diagnosis, measuring treatment effect, and determining prognosis. Interpreting diagnostic test results requires an understanding of key statistical concepts used to evaluate test efficacy. This review explains descriptive statistics and discusses probability, including mutually exclusive and independent events and conditional probability. In the inferential statistics section, a statistical perspective on study design is provided, together with an explanation of how to select appropriate statistical tests. Key concepts in recruiting study samples are discussed, including representativeness and random sampling. Variable types are defined, including predictor, outcome, and covariate variables, and the relationship of these variables to one another. In the hypothesis testing section, we explain how to determine if observed differences between groups are likely to be due to chance. We explain type I and II errors, statistical significance, and study power, followed by an explanation of effect sizes and how confidence intervals can be used to generalize observed effect sizes to the larger population. Statistical tests are explained in four categories: t tests and analysis of variance, proportion analysis tests, nonparametric tests, and regression techniques. We discuss sensitivity, specificity, accuracy, receiver operating characteristic analysis, and likelihood ratios. Measures of reliability and agreement, including κ statistics, intraclass correlation coefficients, and Bland-Altman graphs and analysis, are introduced. PMID:26466186

  4. Statistics 101 for Radiologists.

    PubMed

    Anvari, Arash; Halpern, Elkan F; Samir, Anthony E

    2015-10-01

    Diagnostic tests have wide clinical applications, including screening, diagnosis, measuring treatment effect, and determining prognosis. Interpreting diagnostic test results requires an understanding of key statistical concepts used to evaluate test efficacy. This review explains descriptive statistics and discusses probability, including mutually exclusive and independent events and conditional probability. In the inferential statistics section, a statistical perspective on study design is provided, together with an explanation of how to select appropriate statistical tests. Key concepts in recruiting study samples are discussed, including representativeness and random sampling. Variable types are defined, including predictor, outcome, and covariate variables, and the relationship of these variables to one another. In the hypothesis testing section, we explain how to determine if observed differences between groups are likely to be due to chance. We explain type I and II errors, statistical significance, and study power, followed by an explanation of effect sizes and how confidence intervals can be used to generalize observed effect sizes to the larger population. Statistical tests are explained in four categories: t tests and analysis of variance, proportion analysis tests, nonparametric tests, and regression techniques. We discuss sensitivity, specificity, accuracy, receiver operating characteristic analysis, and likelihood ratios. Measures of reliability and agreement, including κ statistics, intraclass correlation coefficients, and Bland-Altman graphs and analysis, are introduced.

  5. 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.

  6. Agreement between clinical and portable EMG/ECG diagnosis of sleep bruxism.

    PubMed

    Castroflorio, T; Bargellini, A; Rossini, G; Cugliari, G; Deregibus, A; Manfredini, D

    2015-10-01

    The aim of this study was to compare clinical sleep bruxism (SB) diagnosis with an instrumental diagnosis obtained with a device providing electromyography/electrocardiography (EMG/ECG) recordings. Forty-five (N = 45) subjects (19 males and 26 females, mean age 28 ± 11 years) were selected among patients referring to the Gnathology Unit of the Dental School of the University of Torino. An expert clinician assessed the presence of SB based on the presence of one or more signs/symptoms (i.e., transient jaw muscle pain in the morning, muscle fatigue at awakening, presence of tooth wear, masseter hypertrophy). Furthermore, all participants underwent an instrumental recording at home with a portable device (Bruxoff; OT Bioelettronica, Torino, Italy) allowing a simultaneous recording of EMG signals from both the masseter muscles as well as heart frequency. Statistical procedures were performed with the software Statistical Package for the Social Science v. 20.0 (SPSS 20.0; IBM, Milan, Italy). Based on the EMG/ECG analysis, 26 subjects (11 males, 15 females, mean age 28 ± 10 years) were diagnosed as sleep bruxers, whilst 19 subjects (7 males, 12 females, mean age 30 ± 10 years) were diagnosed as non-bruxers. The correlation between the clinical and EMG/ECG SB diagnoses was low (ϕ value = 0.250), with a 62.2% agreement (28/45 subjects) between the two approaches (kappa = 0.248). Assuming instrumental EMG/ECG diagnosis as the standard of reference for definite SB diagnosis in this investigation, the false-positive and false-negative rates were unacceptable for all clinical signs/symptoms. In conclusion, findings from clinical assessment are not related with SB diagnosis performed with a portable EMG/ECG recorder.

  7. Kappa effect pulsational instability for hot extreme helium stars

    SciTech Connect

    Cox, A.N.

    1990-01-01

    A long standing problem for the hydrogen deficient stars has been the mechanism for the pulsation instability for the hottest members of this class. The usual {kappa} mechanism works well for stars that are in the hydrogen and helium ionization instability strip, and this strip extends to perhaps 20,000K at high luminosity. However, several stars are definitely hotter. Investigations for another ionization instability strip, such as for carbon, have always shown that there is not enough carbon to produce a rapid enough increase of opacity with temperature to give the well-known {kappa} effect. This is so even though these hydrogen deficient stars do show enhanced carbon in their spectra. A strong stellar wind can produce the observed hydrogen deficiency. Another popular mechanism is mass loss in a binary system through the Roche lobe. It now is possible that the missing pulsational instability mechanism is the rapid increase of iron lines absorption as the temperature increases above about 150,000K in the low density envelopes of these luminous stars. Recent calculations shows that the n = 3 to n = 3 transitions in iron that were assumed unimportant in the earlier Los Alamos calculations can double or triple the opacity suddenly as the iron lines appear in a very sensitive part of the spectrum of the diffusing photons. It has been proposed that these iron lines also cause the many varieties of normal B star pulsations, and the hydrogen deficient stars are merely another example of this new {kappa} effect for pulsating stars. The extreme helium star V2076 Oph at 31,900K, and 38,900 L{sub {circle dot}} for a mass of 1.4 M{sub {circle dot}} pulsates in the radial fundamental model at about 1 day period with a very large linear growth rate when the iron lines more than double the opacity, but is stable otherwise.

  8. kappa-Opioid receptor signaling and brain reward function.

    PubMed

    Bruijnzeel, Adrie W

    2009-12-11

    The dynorphin-like peptides have profound effects on the state of the brain reward system and human and animal behavior. The dynorphin-like peptides affect locomotor activity, food intake, sexual behavior, anxiety-like behavior, and drug intake. Stimulation of kappa-opioid receptors, the endogenous receptor for the dynorphin-like peptides, inhibits dopamine release in the striatum (nucleus accumbens and caudate putamen) and induces a negative mood state in humans and animals. The administration of drugs of abuse increases the release of dopamine in the striatum and mediates the concomitant release of dynorphin-like peptides in this brain region. The reviewed studies suggest that chronic drug intake leads to an upregulation of the brain dynorphin system in the striatum and in particular in the dorsal part of the striatum/caudate putamen. This might inhibit drug-induced dopamine release and provide protection against the neurotoxic effects of high dopamine levels. After the discontinuation of chronic drug intake these neuroadaptations remain unopposed which has been suggested to contribute to the negative emotional state associated with drug withdrawal and increased drug intake. kappa-Opioid receptor agonists have also been shown to inhibit calcium channels. Calcium channel inhibitors have antidepressant-like effects and inhibit the release of norepinephrine. This might explain that in some studies kappa-opioid receptor agonists attenuate nicotine and opioid withdrawal symptomatology. A better understanding of the role of dynorphins in the regulation of brain reward function might contribute to the development of novel treatments for mood disorders and other disorders that stem from a dysregulation of the brain reward system.

  9. Sex differences in opioid antinociception: kappa and 'mixed action' agonists.

    PubMed

    Craft, R M; Bernal, S A

    2001-08-01

    A number of investigators have shown that male animals are more sensitive than females to the antinociceptive effects of mu-opioid agonists. The present study was conducted to examine sex differences in opioid antinociception in the rat using agonists known to differ in selectivity for and efficacy at kappa- versus mu-receptors. Dose- and time-effect curves were obtained for s.c. U69593, U50488, ethylketazocine, (-)-bremazocine, (-)-pentazocine, butorphanol and nalbuphine on the 50 or 54 degrees C hotplate and warm water tail withdrawal assays; spontaneous locomotor activity was measured 32-52 min post-injection in the same rats. On the hotplate assay, only butorphanol (54 degrees C) and nalbuphine (50 degrees C) were significantly more potent in males than females. On the tail withdrawal assay, all agonists were significantly more potent or efficacious in males than females at one or both temperatures. In contrast, no agonist was consistently more potent in one sex or the other in decreasing locomotor activity. Estrous stage in female rats only slightly influenced opioid effects, accounting for an average of 2.6% of the variance in females' antinociceptive and locomotor responses to drug (50 degrees C experiment). These results suggest that (1) sex differences in antinociceptive effects of opioids are not mu-receptor-dependent, as they may occur with opioids known to have significant kappa-receptor-mediated activity; (2) the mechanisms underlying sex differences in kappa-opioid antinociception may be primarily spinal rather than supraspinal; (3) sex differences in antinociceptive effects of opioid agonists are not secondary to sex differences in their sedative effects. PMID:11418226

  10. Morbidity statistics

    PubMed Central

    Smith, Alwyn

    1969-01-01

    This paper is based on an analysis of questionnaires sent to the health ministries of Member States of WHO asking for information about the extent, nature, and scope of morbidity statistical information. It is clear that most countries collect some statistics of morbidity and many countries collect extensive data. However, few countries relate their collection to the needs of health administrators for information, and many countries collect statistics principally for publication in annual volumes which may appear anything up to 3 years after the year to which they refer. The desiderata of morbidity statistics may be summarized as reliability, representativeness, and relevance to current health problems. PMID:5306722

  11. Solar wind driven dust acoustic instability with Lorentzian kappa distribution

    SciTech Connect

    Arshad, Kashif; Ehsan, Zahida; Khan, S. A.; Mahmood, S.

    2014-02-15

    In a three species electron-ion-dust plasma following a generalized non-Maxwellian distribution function (Lorentzian or kappa), it is shown that a kinetic instability of dust-acoustic mode exists. The instability threshold is affected when such (quasineutral) plasma permeates through another static plasma. Such case is of interest when the solar wind is streaming through the cometary plasma in the presence of interstellar dust. In the limits of phase velocity of the waves larger and smaller than the thermal velocity of dust particles, the dispersion properties and growth rate of dust-acoustic mode are investigated analytically with validation via numerical analysis.

  12. Kappa-casein polymorphisms among cattle breeds and bison herds

    USGS Publications Warehouse

    Cronin, M.A.; Cockett, N.

    1993-01-01

    We identified the HindIII restriction site polymorphism Of kappa-casein in cattle reported by Pinder et al. (Animal Genetics 22, 11, 1991) and found an additonal polymorphism (RsaI) in cattle and bison. The Hin dIII and Rsa I restriction sites were mapped and three haplotypes (alleles) were identified. Preliminary screening of 39 cattle and 71 bison revealed one allele restricted to cattle, one restricted to bison, and one shared by the species. No fixed allelic differences were observed among cattle breeds or among bison herds or subspecies.

  13. NF-kappaB inhibitors for the treatment of inflammatory diseases and cancer.

    PubMed

    Calzado, Marco A; Bacher, Susanne; Schmitz, M Lienhard

    2007-01-01

    The NF-kappaB/Rel signaling system is a paradigm for gene activation in response to inflammatory and menacing stimuli. Given the growing body of evidence showing an important involvement of NF-kappaB for the onset of autoimmune diseases and different types of cancer, NF-kappaB is an important drug target for the adjuvant therapy of these diseases. Great efforts have been made for the development of highly specific NF-kappaB inhibitors, some of them being currently tested in phase II clinical trials. Here we discuss recent progress in the identification of druggable components of the NF-kappaB signaling system and the development and potential use of novel NF-kappaB inhibitors.

  14. Strong Agreement of Nationally Recommended Retention Measures from the Institute of Medicine and Department of Health and Human Services

    PubMed Central

    Rebeiro, Peter F.; Horberg, Michael A.; Gange, Stephen J.; Gebo, Kelly A.; Yehia, Baligh R.; Brooks, John T.; Buchacz, Kate; Silverberg, Michael J.; Gill, John; Moore, Richard D.; Althoff, Keri N.

    2014-01-01

    Objective We sought to quantify agreement between Institute of Medicine (IOM) and Department of Health and Human Services (DHHS) retention indicators, which have not been compared in the same population, and assess clinical retention within the largest HIV cohort collaboration in the U.S. Design Observational study from 2008–2010, using clinical cohort data in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). Methods Retention definitions used HIV primary care visits. The IOM retention indicator was: ≥2 visits, ≥90 days apart, each calendar year. This was extended to a 2-year period; retention required meeting the definition in both years. The DHHS retention indicator was: ≥1 visit each semester over 2 years, each ≥60 days apart. Kappa statistics detected agreement between indicators and C statistics (areas under Receiver-Operating Characteristic curves) from logistic regression analyses summarized discrimination of the IOM indicator by the DHHS indicator. Results Among 36,769 patients in 2008–2009 and 34,017 in 2009–2010, there were higher percentages of participants retained in care under the IOM indicator than the DHHS indicator (80% vs. 75% in 2008–2009; 78% vs. 72% in 2009–2010, respectively) (p<0.01), persisting across all demographic and clinical characteristics (p<0.01). There was high agreement between indicators overall (κ = 0.83 in 2008–2009; κ = 0.79 in 2009–2010, p<0.001), and C statistics revealed a very strong ability to predict retention according to the IOM indicator based on DHHS indicator status, even within characteristic strata. Conclusions Although the IOM indicator consistently reported higher retention in care compared with the DHHS indicator, there was strong agreement between IOM and DHHS retention indicators in a cohort demographically similar to persons living with HIV/AIDS in the U.S. Persons with poorer retention represent subgroups of interest for retention improvement

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

    SciTech Connect

    Eliseev, Roman A. . E-mail: Roman_Eliseev@urmc.rochester.edu; Schwarz, Edward M.; Zuscik, Michael J.; O'Keefe, Regis J.; Drissi, Hicham; Rosier, Randy N.

    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 such 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.

  16. Statistical Diversions

    ERIC Educational Resources Information Center

    Petocz, Peter; Sowey, Eric

    2012-01-01

    The term "data snooping" refers to the practice of choosing which statistical analyses to apply to a set of data after having first looked at those data. Data snooping contradicts a fundamental precept of applied statistics, that the scheme of analysis is to be planned in advance. In this column, the authors shall elucidate the statistical…

  17. 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.

  18. Elevated expression of NF-kappaB in oral submucous fibrosis--evidence for NF-kappaB induction by safrole in human buccal mucosal fibroblasts.

    PubMed

    Ni, Wei-Feng; Tsai, Chung-Hung; Yang, Shun-Fa; Chang, Yu-Chao

    2007-07-01

    Nuclear factor-kappa B (NF-kappaB) is considered to be important in many inflammatory and immune responses. The aim of this study was to compare NF-kappaB expression in normal human buccal mucosa and oral submucous fibrosis (OSF) specimens and further explore the potential mechanism that may lead to induction of NF-kappaB expression. Seventeen OSF and six normal buccal mucosa specimens were examined by immunohistochemistry. Primary human buccal mucosal fibroblasts (BMFs) were established and challenged with safrole, a major polyphenolic compound in the influorescence of Piper betel, by cytotoxicity and western blot assays. Furthermore, glutathione precursor N-acetyl-L-cysteine (NAC), extracellular signal-regulated protein kinase (ERK) inhibitor PD98059, cyclooxygenase-2 (COX-2) inhibitor NS-398, dexamethasone, and cyclosporin A were added to find the possible mechanism. NF-kappaB expression was significantly higher in OSF specimens and expressed mainly by fibroblasts, endothelial cells, and inflammatory cells. Safrole was cytotoxic to BMFs in a dose-dependent manner (p<0.05). Western blot demonstrated highly elevated NF-kappaB protein expression in BMFs stimulated by safrole (p<0.05). In addition, pretreatment with pharmacological agents markedly inhibited the safrole induced-NF-kappaB expression (p<0.05). The result suggests that chewing areca quid may activate NF-kappaB expression that may be involved in the pathogenesis of OSF. NF-kappaB expression induced by safrole in fibroblasts may be mediated by ERK activation and COX-2 signal transduction pathway.

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

    SciTech Connect

    Shibata, Mio; Sato, Tomonobu; Nukiwa, Ryota; Ariga, Tadashi; Hatakeyama, Shigetsugu

    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 of 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.

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

    SciTech Connect

    Bao Xiaoyong; Indukuri, Hemalatha; Liu Tianshuang; Liao Suiling; Tian, Bing; Brasier, Allan R.; Garofalo, Roberto P.; Casola, Antonella

    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. Absence 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.

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

    SciTech Connect

    Santos, M. S. dos; Ziebell, L. F. Gaelzer, R.

    2015-12-15

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

  2. Pharmacological inhibitors of NF-kappaB accelerate apoptosis in chronic lymphocytic leukaemia cells.

    PubMed

    Pickering, B M; de Mel, S; Lee, M; Howell, M; Habens, F; Dallman, C L; Neville, L A; Potter, K N; Mann, J; Mann, D A; Johnson, P W M; Stevenson, F K; Packham, G

    2007-02-22

    Nuclear factor-kappaB (NF-kappaB) is a transcription factor that plays a critical role in the inappropriate survival of various types of malignant cells. Chronic lymphocytic leukaemia (CLL) is the most common B-cell malignancy in the Western world. Although overexpression and regulation of NF-kappaB has been described in CLL, its function remains unclear. Exposure of CLL cells to BAY117082 or Kamebakaurin, potent pharmacological inhibitors of the NF-kappaB pathway, accelerated apoptosis in approximately 70% of cases. Sensitivity to NF-kappaB pathway inhibitors was not related to the prognostic markers VH status, CD38 or Zap70 expression, or to the levels of nuclear NF-kappaB. Normal peripheral B cells were resistant to the apoptosis-inducing effects of these compounds. Cell death induced by the inhibitors was associated with activation of caspase-9 and -3, and loss of mitochondrial membrane polarization, but did not involve changes in the expression of Bcl-2 or Mcl-1. Inhibitors caused an increase in c-jun NH2-terminal kinase activity in CLL, but this did not appear to be important for apoptosis. Microarray analysis identified some potential novel NF-kappaB target genes, including interleukin-16- and the Bcl-2- related survival protein Bcl-w. These results demonstrate that a substantial proportion of CLL are dependent on NF-kappaB for enhanced survival and suggest that inhibition of NF-kappaB may have therapeutic potential.

  3. NF-kappa B inhibition markedly enhances sensitivity of resistant breast cancer tumor cells to tamoxifen.

    PubMed

    deGraffenried, L A; Chandrasekar, B; Friedrichs, W E; Donzis, E; Silva, J; Hidalgo, M; Freeman, J W; Weiss, G R

    2004-06-01

    Studies show that high Akt activity in breast carcinoma is associated with endocrine therapy resistance. Breast cancer cell lines expressing a constitutively active Akt are able to proliferate under reduced estrogen conditions, and are resistant to the growth inhibitory effects of tamoxifen. Understanding the targets of Akt signaling mediating tamoxifen resistance is of clinical significance. One possible target is nuclear factor kappa B (NF-kappa B), a transcription factor that plays a critical role in resistance to apoptosis and the induction of angiogenesis and invasion. In the present study, we found that Akt activity correlated with phosphorylation of I kappa B (the negative regulator of NF-kappa B), NF-kappa B DNA binding and tamoxifen resistance in vivo. Importantly, we found that co-treatment with the NF-kappa B inhibitor, parthenolide, or overexpression of I kappa B superrepressor restored tamoxifen sensitivity to our refractory Akt MCF-7 cells. These data suggest that activation of NF-kappa B via the PI3K/Akt signaling pathway may be a significant mechanism for development of endocrine therapy resistance in breast cancer, and that inhibition of NF-kappa B may be an effective treatment strategy to limit the progression of this disease.

  4. Binding of kappa- and sigma-opiates in rat brain

    SciTech Connect

    Wolozin, B.L.; Nishimura, S.; Pasternak, G.W.

    1982-06-01

    Detailed displacements of (/sup 3/H)dihydromorphine by ketocyclazocine and SKF 10,047, (/sup 3/H)ethylketocyclazocine by SKF 10,047, and (/sup 3/H)SKF 10,047 by ketocyclazocine are all multiphasic, suggesting multiple binding sites. After treating brain tissue in vitro with naloxazone, all displacements lose the initial inhibition of /sup 3/H-ligand binding by low concentrations of unlabeled drugs. Together with Scatchard analysis of saturation experiments, these studies suggest a common site which binds mu-, kappa, and sigma-opiates and enkephalins equally well and with highest affinity (KD less than 1 nM). The ability of unlabeled drugs to displace the low affinity binding of (/sup 3/H)dihydromorphine (KD . 3 nM), (/sup 3/H)ethylketocyclazocine (KD . 4 nM), (/sup 3/H)SKF 10,047 (KD . 6 nM), and D-Ala2-D-Leu5-(/sup 3/H)enkephalin (KD . 5 nM) remaining after treating tissue with naloxazone demonstrates unique pharmacological profiles for each. These results suggest the existence of distinct binding sites for kappa- and sigma-opiates which differ from those sites which selectively bind morphine (mu) and enkephalin (delta).

  5. Protein kinase C{eta} activates NF-{kappa}B in response to camptothecin-induced DNA damage

    SciTech Connect

    Raveh-Amit, Hadas; Hai, Naama; Rotem-Dai, Noa; Shahaf, Galit; Gopas, Jacob; Livneh, Etta

    2011-08-26

    Highlights: {yields} Protein kinase C-eta (PKC{eta}) is an upstream regulator of the NF-{kappa}B signaling pathway. {yields} PKC{eta} activates NF-{kappa}B in non-stressed conditions and in response to DNA damage. {yields} PKC{eta} regulates NF-{kappa}B by activating I{kappa}B kinase (IKK) and inducing I{kappa}B degradation. -- Abstract: The nuclear factor {kappa}B (NF-{kappa}B) family of transcription factors participates in the regulation of genes involved in innate- and adaptive-immune responses, cell death and inflammation. The involvement of the Protein kinase C (PKC) family in the regulation of NF-{kappa}B in inflammation and immune-related signaling has been extensively studied. However, not much is known on the role of PKC in NF-{kappa}B regulation in response to DNA damage. Here we demonstrate for the first time that PKC-eta (PKC{eta}) regulates NF-{kappa}B upstream signaling by activating the I{kappa}B kinase (IKK) and the degradation of I{kappa}B. Furthermore, PKC{eta} enhances the nuclear translocation and transactivation of NF-{kappa}B under non-stressed conditions and in response to the anticancer drug camptothecin. We and others have previously shown that PKC{eta} confers protection against DNA damage-induced apoptosis. Our present study suggests that PKC{eta} is involved in NF-{kappa}B signaling leading to drug resistance.

  6. Statistics Clinic

    NASA Technical Reports Server (NTRS)

    Feiveson, Alan H.; Foy, Millennia; Ploutz-Snyder, Robert; Fiedler, James

    2014-01-01

    Do you have elevated p-values? Is the data analysis process getting you down? Do you experience anxiety when you need to respond to criticism of statistical methods in your manuscript? You may be suffering from Insufficient Statistical Support Syndrome (ISSS). For symptomatic relief of ISSS, come for a free consultation with JSC biostatisticians at our help desk during the poster sessions at the HRP Investigators Workshop. Get answers to common questions about sample size, missing data, multiple testing, when to trust the results of your analyses and more. Side effects may include sudden loss of statistics anxiety, improved interpretation of your data, and increased confidence in your results.

  7. SEER Statistics

    Cancer.gov

    The Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute works to provide information on cancer statistics in an effort to reduce the burden of cancer among the U.S. population.

  8. Cancer Statistics

    MedlinePlus

    ... cancer statistics across the world. U.S. Cancer Mortality Trends The best indicator of progress against cancer is ... the number of cancer survivors has increased. These trends show that progress is being made against the ...

  9. Observation of new states decaying into Lambda(c)(+)Kappa(-)pi(+) and Lambda(c)(+)Kappa(0)/(s)pi(-).

    PubMed

    Chistov, R; Abe, K; Abe, K; Adachi, I; Aihara, H; Anipko, D; Aulchenko, V; Aushev, T; Bakich, A M; Balagura, V; Barberio, E; Bay, A; Bedny, I; Belous, K; Bitenc, U; Bizjak, I; Blyth, S; Bondar, A; Bozek, A; Bracko, M; Brodzicka, J; Browder, T E; Chang, M-C; Chao, Y; Chen, A; Chen, K-F; Chen, W T; Cheon, B G; Choi, Y; Choi, Y K; Chuvikov, A; Cole, S; Dalseno, J; Danilov, M; Dash, M; Dragic, J; Drutskoy, A; Eidelman, S; Epifanov, D; Gabyshev, N; Garmash, A; Gershon, T; Go, A; Gokhroo, G; Golob, B; Gorisek, A; Ha, H; Haba, J; Hara, T; Hayasaka, K; Hayashii, H; Hazumi, M; Heffernan, D; Hokuue, T; Hoshi, Y; Hou, S; Hou, W-S; Hsiung, Y B; Iijima, T; Imoto, A; Inami, K; Ishikawa, A; Itoh, R; Iwasaki, M; Iwasaki, Y; Kang, J H; Katayama, N; Kawai, H; Kawasaki, T; Khan, H R; Kichimi, H; Kim, H J; Kim, H O; Kinoshita, K; Korpar, S; Krizan, P; Krokovny, P; Kumar, R; Kuo, C C; Kuzmin, A; Kwon, Y-J; Leder, G; Lee, J; Lesiak, T; Lin, S-W; Liventsev, D; Mandl, F; Marlow, D; Matsumoto, T; Matyja, A; McOnie, S; Mitaroff, W; Miyabayashi, K; Miyake, H; Miyata, H; Miyazaki, Y; Mizuk, R; Moloney, G R; Nagamine, T; Nakano, E; Nakao, M; Nishida, S; Nitoh, O; Nozaki, T; Ogawa, S; Ohshima, T; Okabe, T; Okuno, S; Olsen, S L; Onuki, Y; Ozaki, H; Pakhlov, P; Pakhlova, G; Palka, H; Park, H; Park, K S; Pestotnik, R; Piilonen, L E; Sakai, Y; Schietinger, T; Schneider, O; Schwartz, A J; Seidl, R; Sevior, M E; Shapkin, M; Shibuya, H; Shwartz, B; Sidorov, V; Singh, J B; Sokolov, A; Somov, A; Soni, N; Stanic, S; Staric, M; Stoeck, H; Sumiyoshi, T; Suzuki, S; Takasaki, F; Tamura, N; Tanaka, M; Taylor, G N; Teramoto, Y; Tian, X C; Tikhomirov, I; Tsuboyama, T; Tsukamoto, T; Uehara, S; Uglov, T; Ueno, K; Uno, S; Usov, Y; Varner, G; Villa, S; Wang, C C; Wang, C H; Wang, M-Z; Watanabe, Y; Won, E; Wu, C-H; Xie, Q L; Yabsley, B D; Yamaguchi, A; Yamashita, Y; Yamauchi, M; Zhang, L M; Zhang, Z P

    2006-10-20

    We report the first observation of two charmed strange baryons that decay into Lambda(c)(+)Kappa(-)pi(+). The broader of the two states is measured to have a mass of 2978.5+/-2.1+/-2.0 MeV/c2 and a width of 43.5+/-7.5+/-7.0 MeV/c2. The mass and width of the narrow state are measured to be 3076.7+/-0.9+/-0.5 MeV/c;{2} and 6.2+/-1.2+/-0.8 MeV/c2, respectively. We also perform a search for the isospin partner states that decay into Lambda(c)(+)Kappa(0)/(s)pi(-) and observe a significant signal at the mass of 3082.8+/-1.8+/-1.5 MeV/c2. The data used for this analysis were accumulated at or near the Upsilon(4S) resonance, using the Belle detector at the e+ e- asymmetric-energy collider KEKB. The integrated luminosity of the data sample used is 461.5 fb(-1). PMID:17155385

  10. Low agreement between the fitnessgram criterion references for adolescents

    PubMed Central

    Coledam, Diogo Henrique Constantino; Batista, João Pedro; Glaner, Maria Fátima

    2015-01-01

    OBJECTIVE: To analyze the association and agreement of fitnessgram reference criteria (RC) for cardiorespiratory fitness, body mass index (BMI) and strength in youth. METHODS: The study included 781 youth, 386 females, aged 10 to 18 years of Londrina-PR. It were performed cardiorespiratory fitness and muscular strength tests and was calculated body mass index. The association between the tests was analyzed using Poisson regression to obtain prevalence ratio (PR) and confidence intervals of 95%, while agreement of the reference criteria was tested by Kappa index. RESULTS: Significant associations were found between cardiorespiratory fitness and BMI (PR=1,49, 1,27-1,75), muscle strength and BMI (PR=1,55, 1,17-2,08), cardiorespiratory fitness and muscle strength (PR=1,81, 1,47-2,24). The agreement between reference criteria ranged from weak to fair, 48.8% (k=0.05, p=0.10) for cardiorespiratory fitness and BMI, 52.9% (k=0.09, p=0.001) for muscle strength and BMI and 38.4% (k=0.22, p<0.001) for cardiorespiratory fitness and muscle strength. CONCLUSIONS: Although RC for cardiorespiratory fitness, muscle strength and BMI are associated, the agreement between them ranged from weak to fair. To evaluate health related physical fitness it is suggest the execution of all tests, since each test has specific characteristics. PMID:25649383

  11. Modulating temporal control of NF-kappaB activation: implications for therapeutic and assay selection.

    PubMed

    Klinke, David J; Ustyugova, Irina V; Brundage, Kathleen M; Barnett, John B

    2008-06-01

    The activation of transcription factor NF-kappaB (nuclear factor-kappaB) plays a central role in the induction of many inflammatory response genes. This process is characterized by either oscillations or stable induction of NF-kappaB nuclear binding. Changes in dynamics of binding result in the expression of distinct subsets of genes leading to different physiological outcomes. We examined NF-kappaB DNA binding activity in lipopolysaccharide (LPS)-stimulated IC-21 cells by electromobility shift assay and nonradioactive transcription factor assay and interpreted the results using a kinetic model of NF-kappaB activation. Both assays detected damped oscillatory behavior of NF-kappaB with differences in sensitivity and reproducibility. 3,4-Dichloropropionaniline (DCPA) was used to modulate the oscillatory behavior of NF-kappaB after LPS stimulation. DCPA is known to inhibit the production of two NF-kappaB-inducible cytokines, IL-6 and tumor necrosis factor alpha, by reducing but not completely abrogating NF-kappaB-induced transcription. DCPA treatment resulted in a potentiation of early LPS-induced NF-kappaB activation. The nonradioactive transcription factor assay, which has a higher signal/noise ratio than the electromobility shift assay, combined with in silico modeling, produced results that revealed changes in NF-kappaB dynamics which, to the best of our knowledge, have never been previously reported. These results highlight the importance of cell type and stimulus specificity in transcription factor activity assessment. In addition, assay selection has important implications for network inference and drug discovery. PMID:18281385

  12. Activation of hippocampal nuclear factor-kappa B by retrieval is required for memory reconsolidation.

    PubMed

    Boccia, Mariano; Freudenthal, Ramiro; Blake, Mariano; de la Fuente, Veronica; Acosta, Gabriela; Baratti, Carlos; Romano, Arturo

    2007-12-01

    Initially, memory is labile and requires consolidation to become stable. However, several studies support that consolidated memories can undergo a new period of lability after retrieval. The mechanistic differences of this process, termed reconsolidation, with the consolidation process are under debate, including the participation of hippocampus. Up to this point, few reports describe molecular changes and, in particular, transcription factor (TF) involvement in memory restabilization. Increasing evidence supports the participation of the TF nuclear factor-kappaB (NF-kappaB) in memory consolidation. Here, we demonstrate that the inhibition of NF-kappaB after memory reactivation impairs retention of a hippocampal-dependent inhibitory avoidance task in mice. We used two independent disruptive strategies to reach this conclusion. First, we administered intracerebroventricular or intrahippocampal sulfasalazine, an inhibitor of IKK (IkappaB kinase), the kinase that activates NF-kappaB. Second, we infused intracerebroventricular or intrahippocampal kappaB decoy, a direct inhibitor of NF-kappaB consisting of a double-stranded DNA oligonucleotide that contains the kappaB consensus sequence. When injected immediately after memory retrieval, sulfasalazine or kappaB decoy (Decoy) impaired long-term retention. In contrast, a one base mutated kappaB decoy (mDecoy) had no effect. Furthermore, we also found NF-kappaB activation in the hippocampus, with a peak 15 min after memory retrieval. This activation was earlier than that found during consolidation. Together, these results indicate that NF-kappaB is an important transcriptional regulator in memory consolidation and reconsolidation in hippocampus, although the temporal kinetics of activation differs between the two processes.

  13. Statistical Physics

    NASA Astrophysics Data System (ADS)

    Hermann, Claudine

    Statistical Physics bridges the properties of a macroscopic system and the microscopic behavior of its constituting particles, otherwise impossible due to the giant magnitude of Avogadro's number. Numerous systems of today's key technologies - such as semiconductors or lasers - are macroscopic quantum objects; only statistical physics allows for understanding their fundamentals. Therefore, this graduate text also focuses on particular applications such as the properties of electrons in solids with applications, and radiation thermodynamics and the greenhouse effect.

  14. Assessment of pharmacogenomic agreement.

    PubMed

    Safikhani, Zhaleh; El-Hachem, Nehme; Quevedo, Rene; Smirnov, Petr; Goldenberg, Anna; Juul Birkbak, Nicolai; Mason, Christopher; Hatzis, Christos; Shi, Leming; Aerts, Hugo Jwl; Quackenbush, John; Haibe-Kains, Benjamin

    2016-01-01

    In 2013 we published an analysis demonstrating that drug response data and gene-drug associations reported in two independent large-scale pharmacogenomic screens, Genomics of Drug Sensitivity in Cancer (GDSC) and Cancer Cell Line Encyclopedia (CCLE), were inconsistent. The GDSC and CCLE investigators recently reported that their respective studies exhibit reasonable agreement and yield similar molecular predictors of drug response, seemingly contradicting our previous findings. Reanalyzing the authors' published methods and results, we found that their analysis failed to account for variability in the genomic data and more importantly compared different drug sensitivity measures from each study, which substantially deviate from our more stringent consistency assessment. Our comparison of the most updated genomic and pharmacological data from the GDSC and CCLE confirms our published findings that the measures of drug response reported by these two groups are not consistent. We believe that a principled approach to assess the reproducibility of drug sensitivity predictors is necessary before envisioning their translation into clinical settings. PMID:27408686

  15. Assessment of pharmacogenomic agreement

    PubMed Central

    Safikhani, Zhaleh; El-Hachem, Nehme; Quevedo, Rene; Smirnov, Petr; Goldenberg, Anna; Juul Birkbak, Nicolai; Mason, Christopher; Hatzis, Christos; Shi, Leming; Aerts, Hugo JWL; Quackenbush, John; Haibe-Kains, Benjamin

    2016-01-01

    In 2013 we published an analysis demonstrating that drug response data and gene-drug associations reported in two independent large-scale pharmacogenomic screens, Genomics of Drug Sensitivity in Cancer (GDSC) and Cancer Cell Line Encyclopedia (CCLE), were inconsistent. The GDSC and CCLE investigators recently reported that their respective studies exhibit reasonable agreement and yield similar molecular predictors of drug response, seemingly contradicting our previous findings. Reanalyzing the authors’ published methods and results, we found that their analysis failed to account for variability in the genomic data and more importantly compared different drug sensitivity measures from each study, which substantially deviate from our more stringent consistency assessment. Our comparison of the most updated genomic and pharmacological data from the GDSC and CCLE confirms our published findings that the measures of drug response reported by these two groups are not consistent. We believe that a principled approach to assess the reproducibility of drug sensitivity predictors is necessary before envisioning their translation into clinical settings. PMID:27408686

  16. The Impact of Statistical Choices on Neonatal Intensive Care Unit Quality Ratings Based on Nosocomial Infection Rates

    PubMed Central

    Lee, Henry Chong; Chien, Alyna T.; Bardach, Naomi S.; Clay, Ted; Gould, Jeffrey B.; Dudley, R. Adams

    2014-01-01

    Objective To examine the extent to which performance assessment methodologies affect the percent of neonatal intensive care units (NICUs) and very low birth weight (VLBW) infants included in performance assessments, distribution of NICU performance ratings, and level of agreement in those ratings. Design Cross-sectional study based on risk-adjusted nosocomial infection rates. Setting NICUs belonging to the California Perinatal Quality Care Collaborative 2007–2008. Participants 126 California NICUs and 10,487 VLBW infants. Main Exposure Three performance assessment choices: 1. Excluding “low-volume” NICUs (those caring for < 30 VLBW infants in a year) vs. a criterion based on confidence intervals, 2. Using Bayesian vs. frequentist hierarchical models, and 3. Pooling data across one vs. two years. Main Outcome Measures Proportion of NICUs and patients included in quality assessment, distribution of ratings for NICUs, and agreement between methods using the kappa statistic. Results Depending on the methods applied, between 51% and 85% of NICUs were included in performance assessment, the percent of VLBW infants included in performance assessment ranged from 72% to 96%, between 76–87% NICUs were considered “average,” and the level of agreement between NICU ratings ranged from 0.26 to 0.89. Conclusions The percent of NICUs included in performance assessment and their ratings can shift dramatically depending on performance measurement methodology. Physicians, payers, and policymakers should continue to closely examine which existing performance assessment methodologies are most appropriate for evaluating pediatric care quality. PMID:21536958

  17. Agreement with Subjects in Lubukusu

    ERIC Educational Resources Information Center

    Diercks, Michael J. K.

    2010-01-01

    This dissertation examines three topics in the morphosyntax of Lubukusu (Bantu, Kenya), all of which are concerned with agreement with subjects: locative inversion, complementizer agreement, and alternative agreement effects in subject extraction. Each topic reports novel Lubukusu data which are both typologically interesting and theoretically…

  18. Mining Agreements with Indian Tribes

    ERIC Educational Resources Information Center

    Luebben, Tom

    1976-01-01

    The article discusses aspects of negotiating agreements for exploration, development, and mining of hard minerals on Indian Reservations. The agreements discussed are typical of copper agreements, but the general points under discussion are applicable to most hard minerals except for uranium, coal, and oil which are substantially different.…

  19. What do measures of agreement (κ) tell us about quality of exposure assessment? Theoretical analysis and numerical simulation

    PubMed Central

    Burstyn, Igor; de Vocht, Frank; Gustafson, Paul

    2013-01-01

    Background The reliability of binary exposure classification methods is routinely reported in occupational health literature because it is viewed as an important component of evaluating the trustworthiness of the exposure assessment by experts. The Kappa statistics (κ) are typically employed to assess how well raters or classification systems agree in a variety of contexts, such as identifying exposed participants in a population-based epidemiological study of risks due to occupational exposures. However, the question we are really interested in is not so much the reliability of an exposure assessment method, although this holds value in itself, but the validity of the exposure estimates. The validity of binary classifiers can be expressed as a method's sensitivity (SN) and specificity (SP), estimated from its agreement with the error-free classifier. Methods and results We describe a simulation-based method for deriving information on SN and SP that can be derived from κ and the prevalence of exposure, since an analytic solution is not possible without restrictive assumptions. This work is illustrated in the context of comparison of job-exposure matrices assessing occupational exposures to polycyclic aromatic hydrocarbons. Discussion Our approach allows the investigators to evaluate how good their exposure-assessment methods truly are, not just how well they agree with each other, and should lead to incorporation of information of validity of expert assessment methods into formal uncertainty analyses in epidemiology. PMID:24302507

  20. 40 CFR 721.1880 - Borate(1-), tris(acetato-.kappa.O)hydro-, sodium, (T-4)-.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...)hydro-, sodium, (T-4)-. 721.1880 Section 721.1880 Protection of Environment ENVIRONMENTAL PROTECTION... New Uses for Specific Chemical Substances § 721.1880 Borate(1-), tris(acetato-.kappa.O)hydro-, sodium... substance identified as borate(1-), tris(acetato-.kappa.O)hydro-, sodium, (T-4)- (PMN P-00-0922; CAS...

  1. 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...

  2. RPAP3 enhances cytotoxicity of doxorubicin by impairing NF-kappa B pathway

    SciTech Connect

    Shimada, Kana; Saeki, Makio; Egusa, Hiroshi; Fukuyasu, Sho; Yura, Yoshiaki; Iwai, Kazuhiro; Kamisaki, Yoshinori

    2011-01-28

    Research highlights: {yields} RNA polymerase II-associated protein 3 (RPAP3) possesses an activity to bind with NEMO and to inhibit the ubiquitination of NEMO. {yields} RPAP3 enhances doxorubicin-induced cell death in breast cancer cell line T-47D through the marked impairment of NF-{kappa}B pathway. {yields} RPAP3 is a novel modulator of NF-{kappa}B pathway in apoptosis induced by anti-cancer chemotherapeutic agents. -- Abstract: Activation of anti-apoptotic gene transcription by NF-{kappa}B (nuclear factor-kappa B) has been reported to be linked with a resistance of cancer cells against chemotherapy. NEMO (NF-{kappa}B essential modulator) interacts with a number of proteins and modulates the activity of NF-{kappa}B pathway. In this study, we revealed that RPAP3 (RNA polymerase II-associated protein 3) possesses an activity to bind with NEMO and to inhibit the ubiquitination of NEMO and that RPAP3 enhances doxorubicin-induced cell death in breast cancer cell line T-47D through the marked impairment of NF-{kappa}B pathway. These results indicate that RPAP3 may be a novel modulator of NF-{kappa}B pathway in apoptosis induced by anti-cancer chemotherapeutic agents.

  3. 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.

  4. 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". PMID:25606415

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

    SciTech Connect

    Arshad, Kashif 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 are 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)].

  6. Orvinols with Mixed Kappa/Mu Opioid Receptor Agonist Activity

    PubMed Central

    2013-01-01

    Dual-acting kappa opioid receptor (KOR) agonist and mu opioid receptor (MOR) partial agonist ligands have been put forward as potential treatment agents for cocaine and other psychostimulant abuse. Members of the orvinol series of ligands are known for their high binding affinity to both KOR and MOR, but efficacy at the individual receptors has not been thoroughly evaluated. In this study, it is shown that a predictive model for efficacy at KOR can be derived, with efficacy being controlled by the length of the group attached to C20 and by the introduction of branching into the side chain. In vivo evaluation of two ligands with the desired in vitro profile confirms both display KOR, and to a lesser extent MOR, activity in an analgesic assay suggesting that, in this series, in vitro measures of efficacy using the [35S]GTPγS assay are predictive of the in vivo profile. PMID:23438330

  7. Orvinols with mixed kappa/mu opioid receptor agonist activity.

    PubMed

    Greedy, Benjamin M; Bradbury, Faye; Thomas, Mark P; Grivas, Konstantinos; Cami-Kobeci, Gerta; Archambeau, Ashley; Bosse, Kelly; Clark, Mary J; Aceto, Mario; Lewis, John W; Traynor, John R; Husbands, Stephen M

    2013-04-25

    Dual-acting kappa opioid receptor (KOR) agonist and mu opioid receptor (MOR) partial agonist ligands have been put forward as potential treatment agents for cocaine and other psychostimulant abuse. Members of the orvinol series of ligands are known for their high binding affinity to both KOR and MOR, but efficacy at the individual receptors has not been thoroughly evaluated. In this study, it is shown that a predictive model for efficacy at KOR can be derived, with efficacy being controlled by the length of the group attached to C20 and by the introduction of branching into the side chain. In vivo evaluation of two ligands with the desired in vitro profile confirms both display KOR, and to a lesser extent MOR, activity in an analgesic assay suggesting that, in this series, in vitro measures of efficacy using the [(35)S]GTPγS assay are predictive of the in vivo profile.

  8. Detection of interstellar boron in front of kappa Orionus

    NASA Technical Reports Server (NTRS)

    Meneguzzi, M.; York, D. G.

    1980-01-01

    The detection of interstellar boron in the direction of kappa Ori, obtained with the Copernicus satellite telescope by observing the B II 1362.46-A resonance line is reported. A B/H concentration ratio of (1.5 + or - 0.7) x 10 to the -10th (2 standard deviation error bar) is obtained. The main uncertainty lies in the determination of the continuum of the star in that wavelength region, dominated by a broad stellar absorption feature. The value inferred for B/H in the interstellar medium is consistent with the solar and stellar values, believed to be the galactic value, and with the theory of the production of B by cosmic rays in the interstellar medium.

  9. Statistical theory of turbulent incompressible multimaterial flow

    SciTech Connect

    Kashiwa, B.

    1987-10-01

    Interpenetrating motion of incompressible materials is considered. ''Turbulence'' is defined as any deviation from the mean motion. Accordingly a nominally stationary fluid will exhibit turbulent fluctuations due to a single, slowly moving sphere. Mean conservation equations for interpenetrating materials in arbitrary proportions are derived using an ensemble averaging procedure, beginning with the exact equations of motion. The result is a set of conservation equations for the mean mass, momentum and fluctuational kinetic energy of each material. The equation system is at first unclosed due to integral terms involving unknown one-point and two-point probability distribution functions. In the mean momentum equation, the unclosed terms are clearly identified as representing two physical processes. One is transport of momentum by multimaterial Reynolds stresses, and the other is momentum exchange due to pressure fluctuations and viscous stress at material interfaces. Closure is approached by combining careful examination of multipoint statistical correlations with the traditional physical technique of kappa-epsilon modeling for single-material turbulence. This involves representing the multimaterial Reynolds stress for each material as a turbulent viscosity times the rate of strain based on the mean velocity of that material. The multimaterial turbulent viscosity is related to the fluctuational kinetic energy kappa, and the rate of fluctuational energy dissipation epsilon, for each material. Hence a set of kappa and epsilon equations must be solved, together with mean mass and momentum conservation equations, for each material. Both kappa and the turbulent viscosities enter into the momentum exchange force. The theory is applied to (a) calculation of the drag force on a sphere fixed in a uniform flow, (b) calculation of the settling rate in a suspension and (c) calculation of velocity profiles in the pneumatic transport of solid particles in a pipe.

  10. Effects of protein-energy malnutrition on NF-kappaB signalling in murine peritoneal macrophages.

    PubMed

    Fock, Ricardo Ambrósio; Rogero, Marcelo Macedo; Vinolo, Marco Aurélio Ramirez; Curi, Rui; Borges, Maria Carolina; Borelli, Primavera

    2010-04-01

    Protein-energy malnutrition (PEM) is an important public health problem affecting millions of people worldwide. PEM decreases resistance to infection, impairing a number of physiological processes. In unstimulated cells, NF-kappaB is kept from binding to its consensus sequence by the inhibitor I kappaB alpha, which retains NF-kappaB in the cytoplasm. Upon various signals, such as lipopolysaccharide (LPS), I kappaB alpha is rapidly degraded and NF-kappaB is induced to translocate into the nucleus, where it activates expression of various genes that participate in the inflammatory response, including those involved in the synthesis of TNF-alpha. TRAF-6 is a cytoplasmic adapter protein that links the stimulatory signal from Toll like receptor-4 to NF-kappaB. The aim of this study was to evaluate the effect of malnutrition on induction of TNF-alpha by LPS in murine peritoneal macrophages. We evaluated peritoneal cellularity, the expression of MyD88, TRAF-6, IKK, I kappaB alpha and NF-kappaB, NF-kappaB activation and TNF-alpha mRNA and protein synthesis in macrophages. Two-month-old male BALB/C mice were submitted to PEM with a low-protein diet that contained 2% protein, compared to 12% protein in the control diet. When the experimental group had lost about 20% of the original body weight, it was used in the subsequent experiments. Malnourished animals presented anemia, leucopenia and severe reduction in peritoneal cavity cellularity. TNF-alpha mRNA and protein levels of macrophages stimulated with LPS were significantly lower in malnourished animals. PEM also decreased TRAF-6 expression and NF-kappaB activation after LPS stimulation. These results led us to conclude that PEM changes NF-kB signalling pathway in macrophages to LPS stimulus.

  11. Requirement of NF-kappaB/Rel for the development of hair follicles and other epidermal appendices.

    PubMed

    Schmidt-Ullrich, R; Aebischer, T; Hülsken, J; Birchmeier, W; Klemm, U; Scheidereit, C

    2001-10-01

    NF-kappaB/Rel transcription factors and IkappaB kinases (IKK) are essential for inflammation and immune responses, but also for bone-morphogenesis, skin proliferation and differentiation. Determining their other functions has previously been impossible, owing to embryonic lethality of NF-kappaB/Rel or IKK-deficient animals. Using a gene targeting approach we have ubiquitously expressed an NF-kappaB super-repressor to investigate NF-kappaB functions in the adult. Mice with suppressed NF-kappaB revealed defective early morphogenesis of hair follicles, exocrine glands and teeth, identical to Eda (tabby) and Edar (downless) mutant mice. These affected epithelial appendices normally display high NF-kappaB activity, suppression of which resulted in increased apoptosis, indicating that NF-kappaB acts as a survival factor downstream of the tumor necrosis factor receptor family member EDAR. Furthermore, NF-kappaB is required for peripheral lymph node formation and macrophage function.

  12. κ-generalized statistics in personal income distribution

    NASA Astrophysics Data System (ADS)

    Clementi, F.; Gallegati, M.; Kaniadakis, G.

    2007-05-01

    Starting from the generalized exponential function exp_{kappa}(x)=(sqrt{1+kappa2x2}+kappa x)^{1/kappa}, with exp 0(x)=exp (x), proposed in reference [G. Kaniadakis, Physica A 296, 405 (2001)], the survival function P>(x)=exp κ(-βxα), where x∈R+, α,β>0, and kappain[0,1), is considered in order to analyze the data on personal income distribution for Germany, Italy, and the United Kingdom. The above defined distribution is a continuous one-parameter deformation of the stretched exponential function P> 0(x)=exp (-βxα) to which reduces as κ approaches zero behaving in very different way in the x→0 and x→∞ regions. Its bulk is very close to the stretched exponential one, whereas its tail decays following the power-law P>(x)˜(2βκ)-1/κx-α/κ. This makes the κ-generalized function particularly suitable to describe simultaneously the income distribution among both the richest part and the vast majority of the population, generally fitting different curves. An excellent agreement is found between our theoretical model and the observational data on personal income over their entire range.

  13. Integrating heterogeneous classifier ensembles for EMG signal decomposition based on classifier agreement.

    PubMed

    Rasheed, Sarbast; Stashuk, Daniel W; Kamel, Mohamed S

    2010-05-01

    In this paper, we present a design methodology for integrating heterogeneous classifier ensembles by employing a diversity-based hybrid classifier fusion approach, whose aggregator module consists of two classifier combiners, to achieve an improved classification performance for motor unit potential classification during electromyographic (EMG) signal decomposition. Following the so-called overproduce and choose strategy to classifier ensemble combination, the developed system allows the construction of a large set of base classifiers, and then automatically chooses subsets of classifiers to form candidate classifier ensembles for each combiner. The system exploits kappa statistic diversity measure to design classifier teams through estimating the level of agreement between base classifier outputs. The pool of base classifiers consists of different kinds of classifiers: the adaptive certainty-based, the adaptive fuzzy k -NN, and the adaptive matched template filter classifiers; and utilizes different types of features. Performance of the developed system was evaluated using real and simulated EMG signals, and was compared with the performance of the constituent base classifiers. Across the EMG signal datasets used, the developed system had better average classification performance overall, especially in terms of reducing classification errors. For simulated signals of varying intensity, the developed system had an average correct classification rate CCr of 93.8% and an error rate Er of 2.2% compared to 93.6% and 3.2%, respectively, for the best base classifier in the ensemble. For simulated signals with varying amounts of shape and/or firing pattern variability, the developed system had a CCr of 89.1% with an Er of 4.7% compared to 86.3% and 5.6%, respectively, for the best classifier. For real signals, the developed system had a CCr of 89.4% with an Er of 3.9% compared to 84.6% and 7.1%, respectively, for the best classifier.

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

    SciTech Connect

    Genetos, Damian C.; Karin, Norman J.; Geist, Derik J.; Donahue, Henry J.; Duncan, Randall L.

    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 the 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.

  15. Discovery of novel small molecule cell type-specific enhancers of NF-kappaB nuclear translocation.

    PubMed

    Gong, Gangli; Xie, Yuli; Liu, Yidong; Rinderspacher, Alison; Deng, Shi-Xian; Feng, Yan; Zhu, Zhengxiang; Tang, Yufei; Wyler, Michael; Aulner, Nathalie; Toebben, Udo; Smith, Deborah H; Branden, Lars; Chung, Caty; Schürer, Stephan; Vidović, Dusica; Landry, Donald W

    2009-02-15

    An IKKbeta inhibitor reported to block NF-kappaB transcriptional activities in Jurkat T cells, was found to enhance NF-kappaB translocation in HUVEC cells. These studies suggested a noncanonical NF-kappaB signaling pathway independent of IKKbeta in HUVEC cells.

  16. 75 FR 40837 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-14

    ....gov . Agreement No.: 011279-027. Title: Latin America Agreement. Parties: ABC Discussion Agreement; Caribbean Shipowners Association; Central America Discussion Agreement; Compania Libra de Navegacion Uruguay... America Discussion Agreement; and Zim Integrated Shipping Services, Ltd. Filing Party: Wayne R. Rohde,...

  17. Byzantine agreement method without authentication

    SciTech Connect

    Reischuk, R.K.

    1983-12-01

    This invention relates to a method for achieving Byzantine agreement without authentication among n 100 communicating processors using event counting and thresholding rather than message exchanges and evaluations.

  18. Statistical Optics

    NASA Astrophysics Data System (ADS)

    Goodman, Joseph W.

    2000-07-01

    The Wiley Classics Library consists of selected books that have become recognized classics in their respective fields. With these new unabridged and inexpensive editions, Wiley hopes to extend the life of these important works by making them available to future generations of mathematicians and scientists. Currently available in the Series: T. W. Anderson The Statistical Analysis of Time Series T. S. Arthanari & Yadolah Dodge Mathematical Programming in Statistics Emil Artin Geometric Algebra Norman T. J. Bailey The Elements of Stochastic Processes with Applications to the Natural Sciences Robert G. Bartle The Elements of Integration and Lebesgue Measure George E. P. Box & Norman R. Draper Evolutionary Operation: A Statistical Method for Process Improvement George E. P. Box & George C. Tiao Bayesian Inference in Statistical Analysis R. W. Carter Finite Groups of Lie Type: Conjugacy Classes and Complex Characters R. W. Carter Simple Groups of Lie Type William G. Cochran & Gertrude M. Cox Experimental Designs, Second Edition Richard Courant Differential and Integral Calculus, Volume I RIchard Courant Differential and Integral Calculus, Volume II Richard Courant & D. Hilbert Methods of Mathematical Physics, Volume I Richard Courant & D. Hilbert Methods of Mathematical Physics, Volume II D. R. Cox Planning of Experiments Harold S. M. Coxeter Introduction to Geometry, Second Edition Charles W. Curtis & Irving Reiner Representation Theory of Finite Groups and Associative Algebras Charles W. Curtis & Irving Reiner Methods of Representation Theory with Applications to Finite Groups and Orders, Volume I Charles W. Curtis & Irving Reiner Methods of Representation Theory with Applications to Finite Groups and Orders, Volume II Cuthbert Daniel Fitting Equations to Data: Computer Analysis of Multifactor Data, Second Edition Bruno de Finetti Theory of Probability, Volume I Bruno de Finetti Theory of Probability, Volume 2 W. Edwards Deming Sample Design in Business Research

  19. Selective inhibition of NF-kappa B blocks osteoclastogenesis and prevents inflammatory bone destruction in vivo.

    PubMed

    Jimi, Eijiro; Aoki, Kazuhiro; Saito, Hiroaki; D'Acquisto, Fulvio; May, Michael J; Nakamura, Ichiro; Sudo, Testuo; Kojima, Takefumi; Okamoto, Fujio; Fukushima, Hidefumi; Okabe, Koji; Ohya, Keiichi; Ghosh, Sankar

    2004-06-01

    Bone destruction is a pathological hallmark of several chronic inflammatory diseases, including rheumatoid arthritis and periodontitis. Inflammation-induced bone loss of this sort results from elevated numbers of bone-resorbing osteoclasts. Gene targeting studies have shown that the transcription factor nuclear factor-kappa B (NF-kappa B) has a crucial role in osteoclast differentiation, and blocking NF-kappa B is a potential strategy for preventing inflammatory bone resorption. We tested this approach using a cell-permeable peptide inhibitor of the I kappa B-kinase complex, a crucial component of signal transduction pathways to NF-kappa B. The peptide inhibited RANKL-stimulated NF-kappa B activation and osteoclastogenesis both in vitro and in vivo. In addition, this peptide significantly reduced the severity of collagen-induced arthritis in mice by reducing levels of tumor necrosis factor-alpha and interleukin-1 beta, abrogating joint swelling and reducing destruction of bone and cartilage. Therefore, selective inhibition of NF-kappa B activation offers an effective therapeutic approach for inhibiting chronic inflammatory diseases involving bone resorption.

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

    SciTech Connect

    Yun, Kangsun; Choi, Yoo Duk; Nam, Jong Hee; Park, Zeeyoung; Im, Sin-Hyeog . E-mail: imsh@gist.ac.kr

    2007-06-08

    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 site 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.

  1. Dimethyl sulfoxide modulates NF-kappa B and cytokine activation in lipopolysaccharide-treated murine macrophages.

    PubMed Central

    Kelly, K A; Hill, M R; Youkhana, K; Wanker, F; Gimble, J M

    1994-01-01

    Antioxidants are protective against septic shock in animal models. Recently, free radical scavengers have been found to inhibit the activation of the NF-kappa B protein in a number of cell lines. This transcriptional regulatory protein binds to the promoters of the proinflammatory cytokines tumor necrosis factor, interleukin-6, and the macrophage inflammatory proteins. The current work examined lipopolysaccharide-induced NF-kappa B activation in the J774 macrophage-like cell line and primary peritoneal macrophages from lipopolysaccharide-responsive (C3HeB/Fej) and -nonresponsive (C3H/HeJ) murine strains. The DNA-binding activity of the NF-kappa B protein directly correlated with mRNA expression for the genes encoding the proinflammatory cytokines and the free radical scavenging enzyme, superoxide dismutase. Both the p50 and p65 NF-kappa B subunits were detected on gel supershift assays. Minimal NF-kappa B activity was observed following exposure of C3H/HeJ macrophages to lipopolysaccharide. The antioxidant dimethyl sulfoxide decreased the level of NF-kappa B activation in the J774 cells. This correlated with decreased expression of cytokine mRNAs and tumor necrosis factor bioactivity. These results suggest that modulation of NF-kappa B activation may provide a mechanism through which antioxidants protect against endotoxemia in murine models. Images PMID:8039880

  2. Structure of the human [kappa]-opioid receptor in complex with JDTic

    SciTech Connect

    Wu, Huixian; Wacker, Daniel; Mileni, Mauro; Katritch, Vsevolod; Han, Gye Won; Vardy, Eyal; Liu, Wei; Thompson, Aaron A.; Huang, Xi-Ping; Carroll, F. Ivy; Mascarella, S. Wayne; Westkaemper, Richard B.; Mosier, Philip D.; Roth, Bryan L.; Cherezov, Vadim; Stevens, Raymond C.

    2013-04-25

    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 diterpene 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.

  3. RelA/NF-{kappa}B transcription factor associates with {alpha}-actinin-4

    SciTech Connect

    Babakov, Vladimir N. Petukhova, Olga A.; Turoverova, Lidia V.; Kropacheva, Irina V.; Tentler, Dmitri G.; Bolshakova, Anastasia V.; Podolskaya, Ekaterina P.; Magnusson, Karl-Eric; Pinaev, George P.

    2008-03-10

    The NF-{kappa}B/RelA family of transcription factors regulates inducible transcription of a large number of genes in response to diverse stimuli. Little is known, however, about the location of NF-{kappa}B in the cytoplasm and the transport mechanism to the nucleus. We found that NF-{kappa}B is associated with the actin-binding protein {alpha}-actinin-4. NF-{kappa}B and {alpha}-actinin-4 co-localized along actin stress fibers and in membrane lamellae in A431 cells. After a 30-min stimulation with EGF or TNF-{alpha}, {alpha}-actinin-4 and p65 were found in the nucleus. Disruption of cytoskeleton by cytochalasin D prior to treatment with TNF-{alpha} led to increase of p65 nuclear translocation. Antibodies to p65 subunit of NF-{kappa}B co-immunoprecipitated {alpha}-actinin-4 from A431 cell lysates and nuclear extracts, but {alpha}-actinin-1 and {beta}-actin were not found in the precipitates. Affinity chromatography experiments displayed that p65 and p50 subunits of NF-{kappa}B can bind to matrix-bound chicken gizzard {alpha}-actinin. We suggest that the {alpha}-actinin-4 is important for the NF-{kappa}B nuclear translocation and its functions inside the nucleus.

  4. Induction of endothelial iNOS by 4-hydroxyhexenal through NF-kappaB activation.

    PubMed

    Lee, J Y; Je, J H; Jung, K J; Yu, B P; Chung, H Y

    2004-08-15

    Lipid peroxidation and its end-product, 4-hydroxyhexenal (HHE), are known to affect redox balance during aging, which causes various degenerative processes including vascular alterations from endothelial cell deterioration. To better understand the molecular action of HHE in the development of vascular abnormalities during the aging process, we investigated whether the upregulation of inducible endothelial nitric oxide synthase (iNOS) by HHE is mediated through nuclear factor kappaB (NF-kappaB) activation. Results indicate that HHE stimulates iNOS by the transcriptional regulation of NF-kappaB activation through cytosolic kappaB degradation inhibitors (IkappaB). Pretreatment with NF-kappaB inhibitors Bay 11-7082 and N-acetyl cysteine (NAC) suppressed the upregulation of iNOS by blunting IkappaB degradation and NF-kappaB binding activity. Because inflammatory stimuli induce iNOS to generate large amounts of nitric oxide (NO), intracellular NO levels in the presence of Bay 11-7082, NAC, and caffeic acid methyl ester were estimated. These inhibitors significantly suppressed the HHE-induced NO levels to a basal level. These findings strongly suggest that in endothelial cells, HHE induces iNOS gene expression through NF-kappaB activation, which can lead to vascular dysfunction by the activation of various proinflammatory genes.

  5. Transcriptional regulation of bcl-2 by nuclear factor kappa B and its significance in prostate cancer.

    PubMed

    Catz, S D; Johnson, J L

    2001-11-01

    This work presents direct evidence that the bcl-2 gene is transcriptionally regulated by nuclear factor-kappa B (NF-kappa B) and directly links the TNF-alpha/NF-kappa B signaling pathway with Bcl-2 expression and its pro-survival response in human prostate carcinoma cells. DNase I footprinting, gel retardation and supershift analysis identified a NF-kappa B site in the bcl-2 p2 promoter. In the context of a minimal promoter, this bcl-2 p2 site 1 increased transcription 10-fold in the presence of the p50/p65 expression vectors, comparable to the increment observed with the consensus NF-kappa B site, while for the full p2 promoter region transcriptional activity was increased sixfold by over-expression of NF-kappa B, an effect eliminated by mutating the bcl-2 p2 site 1. The expression of Bcl-2 has been linked to the hormone-resistant phenotype of advanced prostate cancer. Here we show that an increase in the level of expression of Bcl-2 in the human prostate carcinoma cell line LNCaP observed in response to hormone withdrawal is further augmented by TNF-alpha treatment, and this effect is abated by inhibitors of NF-kappa B. Concomitantly, bcl-2 p2 promoter studies in LNCaP cells show a 40-fold increase in promoter activity after stimulation with TNF-alpha in the absence of hormone.

  6. Distribution of kappa opioid receptors in the brain of young and old male rats

    SciTech Connect

    Maggi, R.; Limonta, P.; Dondi, D.; Martini, L.; Piva, F. )

    1989-01-01

    The experiments to be described have been designed in order to: (a) provide new information on the concentrations of opioid kappa receptors in different regions of the brain of the male rats; and (b) to analyze whether the density of brain kappa receptors might be modified by the process of aging. The concentration of kappa receptors was investigated in the hypothalamus, amygdala, mesencephalon, corpus striatum, hippocampus, thalamus, frontal poles, anterior and posterior cortex collected from male rats of 2 and 19 months of age. {sup 3}H-bremazocine (BRZ) was used as the ligand of kappa receptors, after protection of mu and delta receptors respectively with dihydromorphine and d-ala-d-leu-enkephalin. The results obtained show that: (1) in young male rats, the number of kappa opioid receptors is different in the various brain areas examined. (2) Aging exerts little influence on the number of kappa receptors in the majority of the brain structures considered. However in the amygdala and in the thalamus the number of kappa receptors was increased in old animals.

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

    SciTech Connect

    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.

  8. Role of hydrogen peroxide in NF-kappaB activation: from inducer to modulator.

    PubMed

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

    2009-09-01

    Hydrogen peroxide (H2O2) has been implicated in the regulation of the transcription factor NF-kappaB, a key regulator of the inflammatory process and adaptive immunity. However, no consensus exists regarding the regulatory role played by H2O2. We discuss how the experimental methodologies used to expose cells to H2O2 produce inconsistent results that are difficult to compare, and how the steady-state titration with H2O2 emerges as an adequate tool to overcome these problems. The redox targets of H2O2 in the NF-kappaB pathway--from the membrane to the post-translational modifications in both NF-kappaB and histones in the nucleus--are described. We also review how H2O2 acts as a specific regulator at the level of the single gene, and briefly discuss the implications of this regulation for human health in the context of kappaB polymorphisms. In conclusion, after near 30 years of research, H2O2 emerges not as an inducer of NF-kappaB, but as an agent able to modulate the activation of the NF-kappaB pathway by other agents. This modulation is generic at the level of the whole pathway but specific at the level of the single gene. Therefore, H2O2 is a fine-tuning regulator of NF-kappaB-dependent processes, as exemplified by its dual regulation of inflammation. PMID:19496701

  9. Role of hydrogen peroxide in NF-kappaB activation: from inducer to modulator.

    PubMed

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

    2009-09-01

    Hydrogen peroxide (H2O2) has been implicated in the regulation of the transcription factor NF-kappaB, a key regulator of the inflammatory process and adaptive immunity. However, no consensus exists regarding the regulatory role played by H2O2. We discuss how the experimental methodologies used to expose cells to H2O2 produce inconsistent results that are difficult to compare, and how the steady-state titration with H2O2 emerges as an adequate tool to overcome these problems. The redox targets of H2O2 in the NF-kappaB pathway--from the membrane to the post-translational modifications in both NF-kappaB and histones in the nucleus--are described. We also review how H2O2 acts as a specific regulator at the level of the single gene, and briefly discuss the implications of this regulation for human health in the context of kappaB polymorphisms. In conclusion, after near 30 years of research, H2O2 emerges not as an inducer of NF-kappaB, but as an agent able to modulate the activation of the NF-kappaB pathway by other agents. This modulation is generic at the level of the whole pathway but specific at the level of the single gene. Therefore, H2O2 is a fine-tuning regulator of NF-kappaB-dependent processes, as exemplified by its dual regulation of inflammation.

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

    SciTech Connect

    Reimers, Kerstin . E-mail: reimers.kerstin@mh-hannover.de; 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 cells 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.

  11. Statistics of premixed flame cells

    NASA Technical Reports Server (NTRS)

    Noever, David A.

    1991-01-01

    The statistics of random cellular patterns in premixed flames are analyzed. Agreement is found with a variety of topological relations previously found for other networks, namely, Lewis's law and Aboav's law. Despite the diverse underlying physics, flame cells are shown to share a broad class of geometric properties with other random networks-metal grains, soap foams, bioconvection, and Langmuir monolayers.

  12. Statistics of premixed flame cells

    SciTech Connect

    Noever, D.A. )

    1991-07-15

    The statistics of random cellular patterns in premixed flames are analyzed. Agreement is found with a variety of topological relations previously found for other networks, namely, Lewis's law and Aboav's law. Despite the diverse underlying physics, flame cells are shown to share a broad class of geometric properties with other random networks---metal grains, soap foams, bioconvection, and Langmuir monolayers.

  13. Nalmefene induced elevation in serum prolactin in normal human volunteers: partial kappa opioid agonist activity?

    PubMed

    Bart, Gavin; Schluger, James H; Borg, Lisa; Ho, Ann; Bidlack, Jean M; Kreek, Mary Jeanne

    2005-12-01

    In humans, mu- and kappa-opioid receptor agonists lower tuberoinfundibular dopamine, which tonically inhibits prolactin release. Serum prolactin is, therefore, a useful biomarker for tuberoinfundibular dopamine. The current study evaluated the unexpected finding that the relative mu- and kappa-opioid receptor selective antagonist nalmefene increases serum prolactin, indicating possible kappa-opioid receptor agonist activity. In all, 33 healthy human volunteers (14 female) with no history of psychiatric or substance use disorders received placebo, nalmefene 3 mg, and nalmefene 10 mg in a double-blind manner. Drugs were administered between 0900 and 1000 on separate days via 2-min intravenous infusion. Serial blood specimens were analyzed for serum levels of prolactin. Additional in vitro studies of nalmefene binding to cloned human kappa-opioid receptors transfected into Chinese hamster ovary cells were performed. Compared to placebo, both doses of nalmefene caused significant elevations in serum prolactin (p<0.002 for nalmefene 3 mg and p<0.0005 for nalmefene 10 mg). There was no difference in prolactin response between the 3 and 10 mg doses. Binding assays confirmed nalmefene's affinity at kappa-opioid receptors and antagonism of mu-opioid receptors. [(35)S]GTPgammaS binding studies demonstrated that nalmefene is a full antagonist at mu-opioid receptors and has partial agonist properties at kappa-opioid receptors. Elevations in serum prolactin following nalmefene are consistent with this partial agonist effect at kappa-opioid receptors. As kappa-opioid receptor activation can lower dopamine in brain regions important to the persistence of alcohol and cocaine dependence, the partial kappa agonist effect of nalmefene may enhance its therapeutic efficacy in selected addictive diseases.

  14. Apo CIII gene transcription is regulated by a cytokine inducible NF-kappa B element.

    PubMed Central

    Gruber, P J; Torres-Rosado, A; Wolak, M L; Leff, T

    1994-01-01

    Overproduction of Apo CIII causes elevated plasma triglyceride levels in transgenic animals and is associated with hypertriglyceridemia in humans. The regulation of apo CIII production is likely to play an important role in controlling plasma triglyceride levels. As an initial step in determining the role of transcriptional regulation in the production of apo CIII and in triglyceride metabolism, we have begun to characterize the activity of specific transcriptional regulatory elements in the CIII promoter. In the current study, we have identified and characterized an NF-kappa B regulatory element located 150 nucleotides upstream from the transcriptional start site of the apo CIII gene. Purified NF-kappa B, as well as an NF-kappa B protein in HepG2 cell nuclear extracts, bound specifically to this sequence element. The hepatic protein was induced by phorbol ester (PMA), and reacted with antibodies to the p50 and p65 subunits of NF-kappa B. The NF-kappa B element conferred PMA and IL1-beta inducible transcriptional activity to a heterologous promoter/reporter construct when transfected into HepG2 cells. Analysis of the full length CIII promoter demonstrated that the inducible activity of the NF-kappa B element was suppressed by sequences in the apo CIII enhancer element located approximately 500 nucleotides upstream of the NF-kappa B binding site. A deletion removing the enhancer restored the PMA inducible activity of the NF-kappa B binding site. These results indicate that apo CIII gene expression is regulated by NF-kappa B, and suggest that apo CIII production may be modulated by cellular signals, like inflammatory cytokines, that activate NF-kB. Images PMID:8036173

  15. Agreement Among RTOG Sarcoma Radiation Oncologists in Contouring Suspicious Peritumoral Edema for Preoperative Radiation Therapy of Soft Tissue Sarcoma of the Extremity

    SciTech Connect

    Bahig, Houda; Roberge, David; Bosch, Walter; Levin, William; Petersen, Ivy; Haddock, Michael; Freeman, Carolyn; DeLaney, Thomas F.; Abrams, Ross A.; Indelicato, Danny J.; Baldini, Elizabeth H.; Hitchcock, Ying; Kirsch, David G.; Kozak, Kevin R.; Wolfson, Aaron; and others

    2013-06-01

    Purpose: Peritumoral edema may harbor sarcoma cells. The extent of suspicious edema (SE) included in the treatment volume is subject to clinical judgment, balancing the risk of missing tumor cells with excess toxicity. Our goal was to determine variability in SE delineation by sarcoma radiation oncologists (RO). Methods and Materials: Twelve expert ROs were provided with T1 gadolinium and T2-weighted MR images of 10 patients with high-grade extremity soft-tissue sarcoma. Gross tumor volume, clinical target volume (CTV)3cm (3 cm longitudinal and 1.5 cm radial margin), and CTV2cm (2 cm longitudinal and 1 cm radial margin) were contoured by a single observer. Suspicious peritumoral edema, defined as abnormal signal on T2 images, was independently delineated by all 12 ROs. Contouring agreement was analyzed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics. Results: The mean volumes of GTV, CTV2cm, and CTV3cm were, respectively, 130 cm{sup 3} (7-413 cm{sup 3}), 280 cm{sup 3} and 360 cm{sup 3}. The mean consensus volume computed using the STAPLE algorithm at 95% confidence interval was 188 cm{sup 3} (24-565 cm{sup 3}) with a substantial overall agreement corrected for chance (mean kappa = 0.71; range: 0.32-0.87). The minimum, maximum, and mean volume of SE (excluding the GTV) were 4, 182, and 58 cm{sup 3} (representing a median of 29% of the GTV volume). The median volume of SE not included in the CTV2cm and in the CTV3cm was 5 and 0.3 cm{sup 3}, respectively. There were 3 large tumors with >30 cm{sup 3} of SE not included in the CTV3cm volume. Conclusion: Despite the fact that SE would empirically seem to be a more subjective volume, a substantial or near-perfect interobserver agreement was observed in SE delineation in most cases with high-grade soft-tissue sarcomas of the extremity. A median of 97% of the consensus SE is within the CTV2cm (99.8% within the CTV3cm). In a minority of cases, however, significant

  16. Nuclear factor {kappa}B (NF{kappa}B) and cyclooxygenase-2 (Cox-2) expression in the irradiated colorectum is associated with subsequent histopathological changes

    SciTech Connect

    Yeoh, Ann S.J. . E-mail: ann.yeoh@imvs.sa.gov.au; Bowen, Joanne M.; Gibson, Rachel J.; Keefe, Dorothy M.K.

    2005-12-01

    Purpose: Recent studies have proposed that mucositis development is the same throughout the gastrointestinal tract (GIT), as it is formed from one structure embryologically. Radiation-induced oral mucositis studies have outlined the key involvement of nuclear factor {kappa}B (NF{kappa}B) and cyclooxygenase-2 (Cox-2) in its pathobiology. The purpose of this study was therefore to investigate the expression of NF{kappa}B and Cox-2 in the irradiated colorectum and to correlate these with the associated histopathologic changes. Methods and Materials: Colorectal tissues from 28 colorectal cancer patients treated with preoperative radiotherapy were analyzed for histopathologic changes using a variety of tissue staining methods. The expression of NF{kappa}B and Cox-2 in these tissues was investigated using immunohistochemistry. Changes in expression of these proteins were then correlated with the histopathologic changes. Results: Radiation therapy caused injury to the normal colorectal tissue surrounding tumor site, particularly around the blood vessels. These changes were reflected in changes in NF{kappa}B and Cox-2 expression. Conclusions: We conclude that different regions of the GIT, the colorectum, and oral cavity have similar underlying mechanisms of radiation-induced mucositis. Understanding these mechanisms will allow new approaches to be developed to specifically target steps in the evolution of alimentary mucositis.

  17. Local Administration of NF-{kappa} B Decoy Oligonucleotides to Prevent Restenosis after Balloon Angioplasty: An Experimental Study in New Zealand White Rabbits

    SciTech Connect

    Kalinowski, Marc Viehofer, Kerstin; Hamann, Christine; Barry, James J.; Kleb, Beate; Klose, Klaus Jochen; Wagner, Hans-Joachim; Alfke, Heiko

    2005-04-15

    Purpose. To evaluate the efficacy of NF-{kappa} B oligonucleotides (ODN) administered by local administration with the channeled balloon catheter to prevent restenosis after balloon angioplasty in restenotic iliac arteries of New Zealand white rabbits. Materials and Methods. In vitro, 8000 rabbit vascular smooth muscle cells (rVSMC) where transfected with a liposomal carrier (TfX50) with 100 ng of decoy and scrambled ODN. Inhibition of proliferation was measured using a MTT assay after 24 hours in comparison to control. In vivo, 22 male New Zealand White rabbits were fed a 1% cholesterol diet and received denudation of both common iliac arteries with a 3 mm balloon catheter to induce an arterial stenosis. Four weeks after stenosis induction, local application of NF-{kappa} B in two different concentrations (1 {mu}g: n = 14; 10 {mu}g: n = 8) was performed randomly on one common iliac artery. Scrambled oligonucleotides without specific binding capacities were injected into the contralateral side. The channeled balloon catheter allows simultaneous balloon dilation (8 atm) of the stenosis and local application of a drug solution (2 atm). Four weeks after local drug delivery the animals were killed and the vessels were excised and computerized morphometric measurements were performed. Results. NF-{kappa} B decoy ODN but not scrambled ODN inhibited proliferation of rVSMC in vitro. Following local ODN application in the animals, no acute vascular complications were seen. NF-{kappa} B ODN resulted in a statistically non significant reduction of neointimal area compared to the control group. The neointimal area was 0.97 mm{sup 2} using 1 {mu}g NF-{kappa} B ODN compared to 0.98 mm{sup 2} in the control group. The higher dose resulted in a neointimal area of 0.97 mm{sup 2} compared to 1.07mm{sup 2} at the control side. Conclusions. Local drug delivery of NF-{kappa} B ODN using the 'channeled balloon' catheter could not reduce neointimal hyperplasia in stenostic rabbit iliac

  18. 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.

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

    SciTech Connect

    Hachem, Ahmed; Yacoub, Daniel; Zaid, Younes; Mourad, Walid; Merhi, Yahye

    2012-08-17

    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). Given 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

  20. 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.

  1. Skills agreement. Recipe for success.

    PubMed

    Nolan, Alexis

    2007-06-21

    The aims of the national health Sector Skills Agreement need regional and local implementation by stakeholders to become reality. Work in the East of England will produce a first regional skills agreement later this year. The Harlow Project is producing award winning process on recuitment and retention. PMID:17847967

  2. The Kappa Opioid Receptor: From Addiction to Depression, and Back

    PubMed Central

    Lalanne, Laurence; Ayranci, Gulebru; Kieffer, Brigitte L.; Lutz, Pierre-Eric

    2014-01-01

    Comorbidity is a major issue in psychiatry that notably associates with more severe symptoms, longer illness duration, and higher service utilization. Therefore, identifying key clusters of comorbidity and exploring the underlying pathophysiological mechanisms represent important steps toward improving mental health care. In the present review, we focus on the frequent association between addiction and depression. In particular, we summarize the large body of evidence from preclinical models indicating that the kappa opioid receptor (KOR), a member of the opioid neuromodulatory system, represents a central player in the regulation of both reward and mood processes. Current data suggest that the KOR modulates overlapping neuronal networks linking brainstem monoaminergic nuclei with forebrain limbic structures. Rewarding properties of both drugs of abuse and natural stimuli, as well as the neurobiological effects of stressful experiences, strongly interact at the level of KOR signaling. In addiction models, activity of the KOR is potentiated by stressors and critically controls drug-seeking and relapse. In depression paradigms, KOR signaling is responsive to a variety of stressors, and mediates despair-like responses. Altogether, the KOR represents a prototypical substrate of comorbidity, whereby life experiences converge upon common brain mechanisms to trigger behavioral dysregulation and increased risk for distinct but interacting psychopathologies. PMID:25538632

  3. The kappa opioid receptor: from addiction to depression, and back.

    PubMed

    Lalanne, Laurence; Ayranci, Gulebru; Kieffer, Brigitte L; Lutz, Pierre-Eric

    2014-01-01

    Comorbidity is a major issue in psychiatry that notably associates with more severe symptoms, longer illness duration, and higher service utilization. Therefore, identifying key clusters of comorbidity and exploring the underlying pathophysiological mechanisms represent important steps toward improving mental health care. In the present review, we focus on the frequent association between addiction and depression. In particular, we summarize the large body of evidence from preclinical models indicating that the kappa opioid receptor (KOR), a member of the opioid neuromodulatory system, represents a central player in the regulation of both reward and mood processes. Current data suggest that the KOR modulates overlapping neuronal networks linking brainstem monoaminergic nuclei with forebrain limbic structures. Rewarding properties of both drugs of abuse and natural stimuli, as well as the neurobiological effects of stressful experiences, strongly interact at the level of KOR signaling. In addiction models, activity of the KOR is potentiated by stressors and critically controls drug-seeking and relapse. In depression paradigms, KOR signaling is responsive to a variety of stressors, and mediates despair-like responses. Altogether, the KOR represents a prototypical substrate of comorbidity, whereby life experiences converge upon common brain mechanisms to trigger behavioral dysregulation and increased risk for distinct but interacting psychopathologies. PMID:25538632

  4. Targeted disruption of the porcine immunoglobulin kappa light chain locus.

    PubMed

    Ramsoondar, J; Mendicino, M; Phelps, C; Vaught, T; Ball, S; Monahan, J; Chen, S; Dandro, A; Boone, J; Jobst, P; Vance, A; Wertz, N; Polejaeva, I; Butler, J; Dai, Y; Ayares, D; Wells, K

    2011-06-01

    Inactivation of the endogenous pig immunoglobulin (Ig) loci, and replacement with their human counterparts, would produce animals that could alleviate both the supply and specificity issues of therapeutic human polyclonal antibodies (PAbs). Platform genetics are being developed in pigs that have all endogenous Ig loci inactivated and replaced by human counterparts, in order to address this unmet clinical need. This report describes the deletion of the porcine kappa (κ) light chain constant (Cκ) region in pig primary fetal fibroblasts (PPFFs) using gene targeting technology, and the generation of live animals from these cells via somatic cell nuclear transfer (SCNT) cloning. There are only two other targeted loci previously published in swine, and this is the first report of a targeted disruption of an Ig light chain locus in a livestock species. Pigs with one targeted Cκ allele (heterozygous knockout or ±) were bred together to generate Cκ homozygous knockout (-/-) animals. Peripheral blood mononuclear cells (PBMCs) and mesenteric lymph nodes (MLNs) from Cκ -/- pigs were devoid of κ-containing Igs. Furthermore, there was an increase in lambda (λ) light chain expression when compared to that of wild-type littermates (Cκ +/+). Targeted inactivation of the Ig heavy chain locus has also been achieved and work is underway to inactivate the pig lambda light chain locus.

  5. Cell immobilization in kappa-carrageenan for ethanol production.

    PubMed

    Luong, J H

    1985-12-01

    A combination of extended Monod kinetics and the diffusional equation was used for evaluating the effectiveness factor of entrapped immobilized cells. Based on the kinetics of Zymomonas mobilis reported in the literature, the numerical results have revealed that the problem of mass transfer diffusional restrictions can be neglected by using small beads (1 mm in diameter) with a corresponding cell loading up to 276 g/L gel. On the basis of the numerical results obtained, the application of immobilized cells for continuous ethanol production was investigated. The kappa-carrageenan method was utilized to entrap Z. mobilis CP4, a potential ethanol producer. A two stage fermentation process has also been developed for ethanol production by the Z. mobilis carrageenan-bound cells. About 90 g/L ethanol was produced by immobilized cells at a total residence time of 1.56 h. The ethanol yield was estimated to be 93% of theoretical. The results obtained in this study also indicated that the control of optimum pH in an immobilized cell column is necessary to enhance the rate of ethanol production. PMID:18553626

  6. Does the kappa opioid receptor system contribute to pain aversion?

    PubMed Central

    Cahill, Catherine M.; Taylor, Anna M. W.; Cook, Christopher; Ong, Edmund; Morón, Jose A.; Evans, Christopher J.

    2014-01-01

    The kappa opioid receptor (KOR) and the endogenous peptide-ligand dynorphin have received significant attention due the involvement in mediating a variety of behavioral and neurophysiological responses, including opposing the rewarding properties of drugs of abuse including opioids. Accumulating evidence indicates this system is involved in regulating states of motivation and emotion. Acute activation of the KOR produces an increase in motivational behavior to escape a threat, however, KOR activation associated with chronic stress leads to the expression of symptoms indicative of mood disorders. It is well accepted that KOR can produce analgesia and is engaged in chronic pain states including neuropathic pain. Spinal studies have revealed KOR-induced analgesia in reversing pain hypersensitivities associated with peripheral nerve injury. While systemic administration of KOR agonists attenuates nociceptive sensory transmission, this effect appears to be a stress-induced effect as anxiolytic agents, including delta opioid receptor agonists, mitigate KOR agonist-induced analgesia. Additionally, while the role of KOR and dynorphin in driving the dysphoric and aversive components of stress and drug withdrawal has been well characterized, how this system mediates the negative emotional states associated with chronic pain is relatively unexplored. This review provides evidence that dynorphin and the KOR system contribute to the negative affective component of pain and that this receptor system likely contributes to the high comorbidity of mood disorders associated with chronic neuropathic pain. PMID:25452729

  7. microRNA and NF-kappa B.

    PubMed

    Yuan, Ye; Tong, Lingying; Wu, Shiyong

    2015-01-01

    Nuclear Factor kappa B (NF-κB) plays important roles in regulation of countless cellular functions, including cell cycle and apoptosis. As a versatile transcription factor, NF-κB is a target of a large amount of miRNAs. Abnormal NF-κB activity is frequently associated with an abnormal level of miRNAs, which is found to play critical roles in disease progression including cancer. While the expression and activity of NF-κB can be directly or indirectly up-regulated or downregulated by various miRNAs, NF-κB can also regulate the expression of many miRNAs. Intriguingly, reciprocal regulation between miRNAs and NF-κB, which exists in the form of positive and negative feedback loops, is often observed in various cancers. In this chapter, the mechanisms and roles of miRNA-regulated NF-κB and NF-κB-regulated miRNAs in a variety of cancers will be discussed. The potential therapeutic use of miRNAs that are up- and down-stream of NF-κB signaling pathways as targets for cancer treatment will also be accessed. PMID:26662991

  8. [Statistical materials].

    PubMed

    1986-01-01

    Official population data for the USSR are presented for 1985 and 1986. Part 1 (pp. 65-72) contains data on capitals of union republics and cities with over one million inhabitants, including population estimates for 1986 and vital statistics for 1985. Part 2 (p. 72) presents population estimates by sex and union republic, 1986. Part 3 (pp. 73-6) presents data on population growth, including birth, death, and natural increase rates, 1984-1985; seasonal distribution of births and deaths; birth order; age-specific birth rates in urban and rural areas and by union republic; marriages; age at marriage; and divorces. PMID:12178831

  9. Caught in the act: In vivo molecular imaging of the transcription factor NF-{kappa}B after myocardial infarction

    SciTech Connect

    Tillmanns, Jochen; Carlsen, Harald; Blomhoff, Rune; Valen, Guro; Calvillo, Laura; Ertl, Georg; Bauersachs, Johann; Frantz, Stefan . E-mail: frantz_s@medizin.uni-wuerzburg.de

    2006-04-14

    Nuclear factor {kappa}B (NF-{kappa}B) is a ubiquitous transcription factor activated by various stimuli implicated in heart failure progression. However, its activation in heart failure has not been well defined yet. Therefore, we investigated activation of NF-{kappa}B after myocardial infarction. For First time, we performed serial, non-invasive in vivo molecular imaging of transcription factor activation in the heart. We used mice expressing a luciferase reporter whose transcription is dependent upon NF-{kappa}B activation for up to 8 weeks after myocardial infarction. There was a significant increase of NF-{kappa}B activity with a maximum at day 3 after myocardial infarction when compared to sham controls. Thus, in vivo measurement of the activation of NF-{kappa}B is feasible. NF-{kappa}B activity might play an important role for the remodeling process.

  10. Effect of sodium ion on the affinity of naloxone for the kappa opioid receptor

    SciTech Connect

    Cheney, B.V.; Lahti, R.A.

    1987-03-16

    Several investigators have observed that sodium ion enhances the binding of naloxone to opioid receptors. This effect has generally been attributed to allosteric modulation of the state of the mu receptor. However, a recent claim has been made that the enhancement does not involve a change in the mu receptor, but instead occurs because naloxone becomes a more kappa-specific drug when sodium ion is present in high concentration. Since the claim was not based on experimental evidence from binding studies involving known high-affinity kappa ligands, the authors have investigated the competition of naloxone for the kappa site using (/sup 3/H)U-69593 as the marker for receptor binding. Assays were carried out in the presence and absence of 100 mM NaCl. The results of the study indicate that sodium ion does not increase the affinity of naloxone or U-69593 for the kappa receptor. 9 references, 1 figure.

  11. Formation of electron kappa distributions due to interactions with parallel propagating whistler waves

    SciTech Connect

    Tao, X. Lu, Q.

    2014-02-15

    In space plasmas, charged particles are frequently observed to possess a high-energy tail, which is often modeled by a kappa-type distribution function. In this work, the formation of the electron kappa distribution in generation of parallel propagating whistler waves is investigated using fully nonlinear particle-in-cell (PIC) simulations. A previous research concluded that the bi-Maxwellian character of electron distributions is preserved in PIC simulations. We now demonstrate that for interactions between electrons and parallel propagating whistler waves, a non-Maxwellian high-energy tail can be formed, and a kappa distribution can be used to fit the electron distribution in time-asymptotic limit. The κ-parameter is found to decrease with increasing initial temperature anisotropy or decreasing ratio of electron plasma frequency to cyclotron frequency. The results might be helpful to understanding the origin of electron kappa distributions observed in space plasmas.

  12. Dust ion acoustic solitons in a plasma with kappa-distributed electrons

    SciTech Connect

    Baluku, T. K.; Hellberg, M. A.; Kourakis, I.; Saini, N. S.

    2010-05-15

    Dust ion acoustic solitons in an unmagnetized dusty plasma comprising cold dust particles, adiabatic fluid ions, and electrons satisfying a kappa distribution are investigated using both small amplitude and arbitrary amplitude techniques. Their existence domain is discussed in the parameter space of Mach number M and electron density fraction f over a wide range of values of kappa. For all kappa>3/2, including the Maxwellian distribution, negative dust supports solitons of both polarities over a range in f. In that region of parameter space solitary structures of finite amplitude can be obtained even at the lowest Mach number, the acoustic speed, for all kappa. These cannot be found from small amplitude theories. This surprising behavior is investigated, and it is shown that f{sub c}, the value of f at which the KdV coefficient A vanishes, plays a critical role. In the presence of positive dust, only positive potential solitons are found.

  13. Electrostatic Korteweg-deVries solitary waves in a plasma with Kappa-distributed electrons

    SciTech Connect

    Choi, C.-R.; Min, K.-W.; Rhee, T.-N.

    2011-09-15

    The Korteweg-deVries (KdV) equation that describes the evolution of nonlinear ion-acoustic solitary waves in plasmas with Kappa-distributed electrons is derived by using a reductive perturbation method in the small amplitude limit. We identified a dip-type (negative) electrostatic KdV solitary wave, in addition to the hump-type solution reported previously. The two types of solitary waves occupy different domains on the {kappa} (Kappa index)-V (propagation velocity) plane, separated by a curve corresponding to singular solutions with infinite amplitudes. For a given Kappa value, the dip-type solitary wave propagates faster than the hump-type. It was also found that the hump-type solitary waves cannot propagate faster than V = 1.32.

  14. [Primary structure of the casein macropeptide of kappa casein of buffalo].

    PubMed

    Addeo, F; Mercier, J C

    1977-01-01

    The complete amino acid sequence of Italian water buffalo (Bubalus arnee) caseinomacropeptide, the C-terminal fragment released from kappa-casein by chymosin, has been determined. It contains 64 amino acid residues including one phosphoserine and differs from its bovine (Bos taurus) B counterpart by 10 amino acid substitutions. The sequence of the last 11 amino acid residues of para-kappa-casein is also reported. In relation to the Ala148/Asp substitution which is responsible for the different electrophoretic behaviour of bovine kappa-caseins B and A, water buffalo kappa-casein is homologous to the bovine variant B. It is suggested that a variant Thr136-Ala148 might be the wild type of the Bos genus.

  15. Federal Facility Agreement progress report

    SciTech Connect

    Not Available

    1993-10-01

    The (SRS) Federal Facility Agreement (FFA) was made effective by the US. Environmental Protection Agency Region IV (EPA) on August 16, 1993. To meet the reporting requirements in Section XXV of the Agreement, the FFA Progress Report was developed. The FFA Progress Report is the first of a series of quarterly progress reports to be prepared by the SRS. As such this report describes the information and action taken to September 30, 1993 on the SRS units identified for investigation and remediation in the Agreement. This includes; rubble pits, runoff basins, retention basin, seepage basin, burning pits, H-Area Tank 16, and spill areas.

  16. Suspension agreements: The status quota

    SciTech Connect

    1996-01-01

    Since the initial filing of anti-dumping actions uranium imports from the former Soviet Union, a maze of filings, agreements, amendments, bills, measures, and deals have emerged on which only the closest observers remain current. Even with all the actions that have taken place, none of the parties appear content with the status quo and changes to the agreements are ongoing. Given this dynamic state of affairs, a recap of events and a summary of the current agreements is helpful for understanding the concerns of the involved parties and digesting future events.

  17. Vesnarinone suppresses TNF-induced activation of NF-kappa B, c-Jun kinase, and apoptosis.

    PubMed

    Manna, S K; Aggarwal, B B

    2000-06-01

    Vesnarinone, a synthetic quinolinone derivative used in the treatment of cardiac failure, exhibits immunomodulatory, anti-inflammatory, and cell growth regulatory properties. The mechanisms underlying these properties are not understood, but due to the critical role of nuclear transcription factor NF-kappa B in these responses, we hypothesized that vesnarinone must modulate NF-kappa B activation. We investigated the effect of vesnarinone on NF-kappa B activation induced by inflammatory agents. Vesnarinone blocked TNF-induced activation of NF-kappa B in a concentration- and time-dependent manner. This effect was mediated through inhibition of phosphorylation and degradation of I kappa B alpha, an inhibitor of NF-kappa B. The effects of vesnarinone were not cell type specific, as it blocked TNF-induced NF-kappa B activation in a variety of cells. NF-kappa B-dependent reporter gene transcription activated by TNF was also suppressed by vesnarinone. The TNF-induced NF-kappa B activation cascade involving TNF receptor 1-TNF receptor associated death domain-TNF receptor associated factor 2 NF-kappa B-inducing kinase-IKK was interrupted at the TNF receptor associated factor 2 and NF-kappa B-inducing kinase sites by vesnarinone, thus suppressing NF-kappa B reporter gene expression. Vesnarinone also blocked NF-kappa B activation induced by several other inflammatory agents, inhibited the TNF-induced activation of transcription factor AP-1, and suppressed the TNF-induced activation of c-Jun N-terminal kinase and mitogen-activated protein kinase kinase. TNF-induced cytotoxicity, caspase activation, and lipid peroxidation were also abolished by vesnarinone. Overall, our results indicate that vesnarinone inhibits activation of NF-kappa B and AP-1 and their associated kinases. This may provide a molecular basis for vesnarinone's ability to suppress inflammation, immunomodulation, and growth regulation.

  18. TLR4 activates NF-{kappa}B in human ovarian granulosa tumor cells

    SciTech Connect

    Woods, Dori C.; Johnson, A.L.

    2011-06-17

    Highlights: {yields} TLR4 is expressed in human ovarian granulosa tumor cells. {yields} Acting through TLR4, LPS and HSP60 induce a NF{kappa}B signaling cascade in human ovarian granulosa tumor cells. {yields} NF{kappa}B activation or inhibition did not alter chemosensitivity to TRAIL or cisplatin. -- Abstract: Previous studies have demonstrated expression of Toll-like receptors (TLRs) in the surface epithelium of normal ovaries (OSE) and in epithelial ovarian tumors. Most notably, OSE-derived cancers express TLR4, which activates the nuclear factor-kappa B (NF-{kappa}B) signaling cascade as a mediator of inflammatory response. Currently, there is considerable interest in elucidating the role of TLR-mediated signaling in cancers. Nevertheless, the expression of TLRs in granulosa cell tumors (GCTs) of the ovary, and the extent to which GCT expression of TLRs may influence cell-signaling pathways and/or modulate the efficacy of chemotherapeutics, has yet to be determined. In the present study, human GCT lines (COV434 and KGN) were utilized to evaluate expression of functional TLR4. TLR4 is expressed in GCT cell lines and ligation of TLR4 with bacterial lipopolysaccharide (LPS) led to I{kappa}B degradation and activation of NF-{kappa}B. NF-{kappa}B activation was confirmed by nuclear localization of NF-{kappa}B p65 following treatment with LPS and the naturally occurring ligand, HSP60. Notably, immunoneutralization of TLR4 blocked nuclear localization, and inhibition of NF-{kappa}B signaling attenuated LPS-induced TNF{alpha} plus increased doubling time in both cell lines. Contradictory to reports using human OSE cell lines, inhibition of NF-{kappa}B signaling failed to sensitize GCT lines to TRAIL or cisplatin. In summary, findings herein are the first to demonstrate a functional TLR-signaling pathway specifically in GCTs, and indicate that in contrast to OSE-derived cancers, inhibition of NF-{kappa}B does not sensitize GCTs to TRAIL or cisplatin.

  19. A mechanistic insight into a proteasome-independent constitutive inhibitor kappaBalpha (IkappaBalpha) degradation and nuclear factor kappaB (NF-kappaB) activation pathway in WEHI-231 B-cells.

    PubMed Central

    Shumway, Stuart D; Miyamoto, Shigeki

    2004-01-01

    Inducible activation of the transcription factor NF-kappaB (nuclear factor kappaB) is classically mediated by proteasomal degradation of its associated inhibitors, IkappaBalpha (inhibitory kappaBalpha) and IkappaBbeta. However, certain B-lymphocytes maintain constitutively nuclear NF-kappaB activity (a p50-c-Rel heterodimer) which is resistant to inhibition by proteasome inhibitors. This activity in the WEHI-231 B-cell line is associated with continual and preferential degradation of IkappaBalpha, which is also unaffected by proteasome inhibitors. Pharmacological studies indicated that there was a correlation between inhibition of IkappaBalpha degradation and constitutive p50-c-Rel activity. Domain analysis of IkappaBalpha by deletion mutagenesis demonstrated that an N-terminal 36-amino-acid sequence of IkappaBalpha represented an instability determinant for constitutive degradation. Moreover, domain grafting studies indicated that this sequence was sufficient to cause IkappaBbeta, but not chloramphenicol acetyltransferase, to be rapidly degraded in WEHI-231 B-cells. However, this sequence was insufficient to target IkappaBbeta to the non-proteasome degradation pathway, suggesting that there was an additional cis-element(s) in IkappaBalpha that was required for complete targeting. Nevertheless, the NF-kappaB pool associated with IkappaBbeta now became constitutively active by virtue of IkappaBbeta instability in these cells. These findings further support the notion that IkappaB instability governs the maintenance of constitutive p50-c-Rel activity in certain B-cells via a unique degradation pathway. PMID:14763901

  20. USING KAPPA FUNCTIONS TO CHARACTERIZE OUTER HELIOSPHERE PROTON DISTRIBUTIONS IN THE PRESENCE OF CHARGE-EXCHANGE

    SciTech Connect

    Zirnstein, E. J.; McComas, D. J. E-mail: dmccomas@swri.edu

    2015-12-10

    Kappa functions have long been used in the analysis and modeling of suprathermal particles in various space plasmas. In situ observations of the supersonic solar wind show its distribution contains a cold ion core and power-law tail, which is well-represented by a kappa function. In situ plasma observations by Voyager, as well as observations of energetic neutral atom (ENA) spectra by the Interstellar Boundary Explorer (IBEX), showed that the compressed and heated inner heliosheath (IHS) plasma beyond the termination shock can also be represented by a kappa function. IBEX exposes the IHS plasma properties through the detection of ENAs generated by charge-exchange in the IHS. However, charge-exchange modifies the plasma as it flows through the IHS, and makes it difficult to ascertain the parent proton distribution. In this paper we investigate the evolution of proton distributions, initially represented by a kappa function, that experience losses due to charge-exchange in the IHS. In the absence of other processes, it is no longer representable by a single kappa function due to the energy-dependent, charge-exchange process. While one can still fit a kappa function to the evolving proton distribution over limited energy ranges, this yields fitting parameters (pseudo-density, pseudo-temperature, pseudo-kappa index) that depend on the energy range of the fit. We discuss the effects of fitting a kappa function to the IHS proton distribution over limited energy ranges, its dependence on the initial proton distribution properties at the termination shock, and implications for understanding the observations.

  1. "DAKLI": a multipurpose ligand with high affinity and selectivity for dynorphin (kappa opioid) binding sites.

    PubMed Central

    Goldstein, A; Nestor, J J; Naidu, A; Newman, S R

    1988-01-01

    We describe a synthetic ligand, "DAKLI" (Dynorphin A-analogue Kappa LIgand), related to the opioid peptide dynorphin A. A single reactive amino group at the extended carboxyl terminus permits various reporter groups to be attached, such as 125I-labeled Bolton-Hunter reagent, fluorescein isothiocyanate, or biotin. These derivatives have high affinity and selectivity for the dynorphin (kappa opioid) receptor. An incidental finding is that untreated guinea pig brain membranes have saturable avidin binding sites. PMID:2902630

  2. Using Kappa Functions to Characterize Outer Heliosphere Proton Distributions in the Presence of Charge-exchange

    NASA Astrophysics Data System (ADS)

    Zirnstein, E. J.; McComas, D. J.

    2015-12-01

    Kappa functions have long been used in the analysis and modeling of suprathermal particles in various space plasmas. In situ observations of the supersonic solar wind show its distribution contains a cold ion core and power-law tail, which is well-represented by a kappa function. In situ plasma observations by Voyager, as well as observations of energetic neutral atom (ENA) spectra by the Interstellar Boundary Explorer (IBEX), showed that the compressed and heated inner heliosheath (IHS) plasma beyond the termination shock can also be represented by a kappa function. IBEX exposes the IHS plasma properties through the detection of ENAs generated by charge-exchange in the IHS. However, charge-exchange modifies the plasma as it flows through the IHS, and makes it difficult to ascertain the parent proton distribution. In this paper we investigate the evolution of proton distributions, initially represented by a kappa function, that experience losses due to charge-exchange in the IHS. In the absence of other processes, it is no longer representable by a single kappa function due to the energy-dependent, charge-exchange process. While one can still fit a kappa function to the evolving proton distribution over limited energy ranges, this yields fitting parameters (pseudo-density, pseudo-temperature, pseudo-kappa index) that depend on the energy range of the fit. We discuss the effects of fitting a kappa function to the IHS proton distribution over limited energy ranges, its dependence on the initial proton distribution properties at the termination shock, and implications for understanding the observations.

  3. High glucose induced nuclear factor kappa B mediated inhibition of endothelial cell migration.

    PubMed

    Hamuro, Masao; Polan, Jodie; Natarajan, Mohan; Mohan, Sumathy

    2002-06-01

    Delayed wound healing and accelerated atherosclerosis are common vascular complications of diabetes mellitus. Although elevated blood glucose level is the major contributing factor, mechanisms that mediate these complications are not clearly understood. In the present study, we have demonstrated that elevated glucose inhibits endothelial cell migration, thereby delaying wound healing. Our results clearly indicated that high glucose (10 or 30 mM) induced activation of nuclear factor kappa B (NF-kappaB) inhibited endothelial cell migration (P<0.05). High glucose induced NF-kappaB DNA binding activity may mediate this inhibition of migration by regulating intracellular nitric oxide. In vitro wound healing model in human aortic endothelial cells (HAEC) were used to evaluate cell migration under the influence of high glucose. The migration inhibited by high glucose was restored by NF-kappaB inhibitors (including E3-4-methylphenyl sulfonyl-2-propenenitrile, N-tosyl-Lys-chloromethylketone (TLCK), or over-expression of inhibitor subunit of kappaB) and endothelial nitric oxide synthase inhibitors (N-methyl-L-arginine (L-NMMA); and Nomega-nitro-L-arginine methyl ester (L-NAME)). Furthermore, NF-kappaB inhibitors attenuated high glucose induced eNOS expression and intracellular nitric oxide (NO) production. Cytoskeletal immunofluorescence staining confirmed differences in actin distribution in HAEC incubated in high glucose in the presence or absence of NF-kappaB and NO inhibitors, explaining the differences observed in migration. In summary, our results for the first time suggest therapeutic strategies involving inhibition of NF-kappaB activation induced by high glucose, which may improve wound healing and help avoid some of the vascular complications of diabetes.

  4. NF-kappaB signaling differentially regulates influenza virus RNA synthesis.

    PubMed

    Kumar, Naveen; Xin, Zhong-Tao; Liang, Yuhong; Ly, Hinh; Liang, Yuying

    2008-10-01

    The NF-kappaB signaling pathway has previously been shown to be required for efficient influenza A virus replication, although the molecular mechanism is not well understood. In this study, we identified a specific step of the influenza virus life cycle that is influenced by NF-kappaB signaling by using two known NF-kappaB inhibitors and a variety of influenza virus-specific assays. The results of time course experiments suggest that the NF-kappaB inhibitors Bay11-7082 and ammonium pyrrolidinedithiocarbamate inhibited an early postentry step of viral infection, but they did not appear to affect the nucleocytoplasmic trafficking of the viral ribonucleoprotein complex. Instead, we found that the levels of influenza virus genomic RNA (vRNA), but not the corresponding cRNA or mRNA, were specifically reduced by the inhibitors in virus-infected cells, indicating that NF-kappaB signaling is intimately involved in the vRNA synthesis. Furthermore, we showed that the NF-kappaB inhibitors specifically diminished influenza virus RNA transcription from the cRNA promoter but not from the vRNA promoter in a reporter assay, a result which is consistent with data obtained from virus-infected cells. The overexpression of the p65 NF-kappaB molecule could not only eliminate the inhibition but also activate influenza virus RNA transcription from the cRNA promoter. Finally, using p65-specific small interfering RNA, we have shown that p65 knockdown reduced the levels of influenza virus replication and vRNA synthesis. In summary, we have provided evidence showing, for the first time, that the NF-kappaB host signaling pathway can differentially regulate influenza virus RNA synthesis, which may also offer some new perspectives into understanding the host regulation of RNA synthesis by other RNA viruses.

  5. TYPE III RADIO BURSTS IN CORONAL PLASMAS WITH KAPPA PARTICLE DISTRIBUTIONS

    SciTech Connect

    Li, B.; Cairns, Iver H.

    2013-02-01

    We present the first simulations of type III bursts produced in the corona with suprathermal non-Maxwellian background particles, as inferred from solar wind data and proposed by theories for the corona and solar wind. The coronal background particles are assumed to follow kappa ({kappa}) distributions. The predicted f{sub p} emission of type III bursts is sensitive via the {kappa} index to the presence of suprathermal background particles, where f{sub p} is the local plasma frequency. The simulations show that (1) the speeds v{sub b} of type III beams are much larger (e.g., v{sub b} Almost-Equal-To 0.58c for {kappa} = 5) and so type III bursts drift much faster for low {kappa} ({<=}5) background plasmas than for Maxwellian backgrounds (producing v{sub b} < 0.3c), and (2) f{sub p} emission generated in a {kappa}-distributed background corona has a larger total bandwidth than in a Maxwellian background, for similar onset frequencies. Type III beams are thus more persistent, i.e., extending over larger distances, in {kappa}-distributed corona. Consequently, observations of fast-drifting coronal type III bursts and associated fast electron beams suggest that the ambient electrons in the corona are {kappa}-distributed, at least when such bursts are observed. These results support, from the new viewpoint of nonthermal radio emission, the occasional presence of suprathermal background electrons in the corona and the associated mechanisms (e.g., 'velocity filtration') for coronal heating and solar wind acceleration. The new results also help resolve longstanding issues regarding the speeds and persistence of type III beams, and the production of remotely observable levels of f{sub p} emission despite severe losses during propagation.

  6. Thromboxane synthase suppression induces lung cancer cell apoptosis via inhibiting NF-{kappa}B

    SciTech Connect

    Leung, Kin Chung; Li, Ming-Yue; Leung, Billy C.S.; Hsin, Michael K.Y.; Mok, Tony S.K.; Underwood, Malcolm J.; Chen, George G.

    2010-12-10

    Accumulating evidence shows that the inhibition of thromboxane synthase (TXS) induced apoptosis in cancer cells. TXS inhibitor 1-Benzylimidzole (1-BI) can trigger apoptosis in lung cancer cells but the mechanism is not fully defined. In this study, lung cancer cells were treated with 1-BI. In this study, the level of reactive oxygen species (ROS) was measured and NF-{kappa}B activity was determined in human lung cancer cells. The roles of ROS and NF-{kappa}B in 1-BI-mediated cell death were analyzed. The results showed that 1-BI induced ROS generation but decreased the activity of NF-{kappa}B by reducing phosphorylated I{kappa}B{alpha} (p-I{kappa}B{alpha}) and inhibiting the translocation of p65 into the nucleus. In contrast to 1-BI, antioxidant N-acetyl cysteine (NAC) stimulated cell proliferation and significantly protected the cells from 1-BI-mediated cell death by neutralizing ROS. Collectively, apoptosis induced by 1-BI is associated with the over-production of ROS and the reduction of NF-{kappa}B. Antioxidants can significantly block the inhibitory effect of 1-BI.

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

    SciTech Connect

    Greenberg, Harly; Ye Xiaobing; Wilson, David; Htoo, Aung K.; Hendersen, Todd; Liu Shufang . E-mail: sliu@lij.edu

    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 eliminated 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.

  8. Improvement of Pulping Uniformity by Measurement of Single Fiber Kappa Number

    SciTech Connect

    Richard R. Gustafson; James B. Callis

    2001-11-20

    A method to measure the kappa of single fibers by staining with a fluorescent dye, Acridine Orange (AO), has been developed. This method is now applied to develop and automated flow-through instrument that permits routine kappa analysis on thousands of images of AO stained fibers to give the fiber kappa number distribution of a pulp sample in a few minutes. The design and operation of the instrument are similar to that of a flow cytometer but with the addition of extensive fiber imaging capability. Fluorescence measurements in the flow-through instrument are found to be consistent with those made with fluorescence microscope provided the signal processing in the flow-thou instrument is handled propertly. The kappa distributions of pulps that were analyzed by means of a density gradient column are compared to those measured with the flow-through instrument with good results. The kappa distributions of various laboratory pulps and commercial pulps have been measured. It has been found that all pulps are non-uniform but that ommercial pulps generally have broader kappa distributions thatn their laboratory counterparts. The effects of different pulping methods and chip pretreatments on pulp uniformity are discussed in the report. Finally, the application of flow-through fluorescence technology to other single fiber measurements are presented.

  9. Formation of Kappa Distribution Functions and Eddy Diffusion in the Magnetosphere of the Earth

    NASA Astrophysics Data System (ADS)

    Antonova, Elizaveta; Stepanova, Marina; Kirpichev, Igor; Vovchenko, Vadim; Ovchinnikov, Ilyav

    2016-07-01

    One of the main features of collisionless magnetospheric plasma is the comparatively quick relaxation of distribution functions to kappa distributions. The form of the kappa distribution consists of a Maxwellian core at low energies and a power law spectrum at high energies. Kappa functions describe particle distributions for the systems that are in stationary state but out of thermal equilibrium. Simultaneous determination of the parameters of kappa distributions in different magnetospheric regions is important for understanding the role of different processes of particle acceleration and relaxation of kappa distribution functions to the Maxwellian ones. We analyze the applicability of kappa approximation for different magnetocpheric regions using the data of the Time History of Events and Macroscale Interactions during Substorms spacecraft (THEMIS) mission. We selected events when at least four satellites of THEMIS mission were aligned along the tail between approximately 7 and 30Re. It was found that for the majority of events the values of power index is increased tailwards. We consider such feature as the result of the existence of the inner magnetosphere sources of particle acceleration. We analyze the role of regular bulk transport and the turbulent transport by eddies of different scale in the formation of observed dependences.

  10. Misestimation of temperature when applying Maxwellian distributions to space plasmas described by kappa distributions

    NASA Astrophysics Data System (ADS)

    Nicolaou, Georgios; Livadiotis, George

    2016-11-01

    This paper presents the misestimation of temperature when observations from a kappa distributed plasma are analyzed as a Maxwellian. One common method to calculate the space plasma parameters is by fitting the observed distributions using known analytical forms. More often, the distribution function is included in a forward model of the instrument's response, which is used to reproduce the observed energy spectrograms for a given set of plasma parameters. In both cases, the modeled plasma distribution fits the measurements to estimate the plasma parameters. The distribution function is often considered to be Maxwellian even though in many cases the plasma is better described by a kappa distribution. In this work we show that if the plasma is described by a kappa distribution, the derived temperature assuming Maxwell distribution can be significantly off. More specifically, we derive the plasma temperature by fitting a Maxwell distribution to pseudo-data produced by a kappa distribution, and then examine the difference of the derived temperature as a function of the kappa index. We further consider the concept of using a forward model of a typical plasma instrument to fit its observations. We find that the relative error of the derived temperature is highly depended on the kappa index and occasionally on the instrument's field of view and response.

  11. DSHARK: A dispersion relation solver for obliquely propagating waves in bi-kappa-distributed plasmas

    NASA Astrophysics Data System (ADS)

    Astfalk, Patrick; Görler, Tobias; Jenko, Frank

    2015-09-01

    Satellite measurements suggest that space plasmas often exhibit bi-kappa particle distributions with high-energy tails instead of simple Maxwellians. The presence of suprathermal particles significantly alters the plasmas' dispersion properties compared to purely Maxwellian scenarios. In the past, wave propagation in magnetized, bi-kappa plasmas was almost exclusively addressed for parallel propagating modes only. To enable a systematic study of both parallel and oblique wave propagation, the new kinetic dispersion relation solver Dispersion Solver for Homogeneous Plasmas with Anisotropic Kappa Distributions (DSHARK) was developed and is presented in this work. DSHARK is an iterative root-finding algorithm which is based on Summers et al. (1994) who derived the dielectric tensor for plasmas with bi-kappa-distributed particles. After a brief discussion of kappa distributions, we present the kinetic theory and the numerical methods implemented in DSHARK and verify the code by considering several test cases. Then, we apply DSHARK to the oblique firehose instability to initiate a more extensive work which will be addressed in the future. A systematic investigation of the dispersion properties of bi-kappa-distributed plasmas is expected to lead to a deeper understanding of wave propagation and instability growth in the solar wind.

  12. Primary structure and functional expression of a guinea pig kappa opioid (dynorphin) receptor.

    PubMed Central

    Xie, G X; Meng, F; Mansour, A; Thompson, R C; Hoversten, M T; Goldstein, A; Watson, S J; Akil, H

    1994-01-01

    A full-length cDNA encoding the guinea pig kappa opioid (dynorphin) receptor has been isolated. The deduced protein contains 380 aa and seven hydrophobic alpha-helices characteristic of the G protein-coupled receptors. This receptor is 90% identical to the mouse and rat kappa receptors, with the greatest level of divergence in the N-terminal region. When expressed in COS-7 cells, the receptor displays high affinity and stereospecificity toward dynorphin peptides and other kappa-selective opioid ligands such as U50, 488. It does not bind the mu- and delta-selective opioid ligands. The expressed receptor is functionally coupled to G protein(s) to inhibit adenylyl cyclase and Ca2+ channels. The guinea pig kappa receptor mRNA is expressed in many brain areas, including the cerebellum, a pattern that agrees well with autoradiographic maps of classical guinea pig kappa binding sites. Species differences in the pharmacology and mRNA distribution between the cloned guinea pig and rat kappa receptors may be worthy of further examination. Images PMID:8170987

  13. Expression of NF-kappaB and cytokines in chronic rejection of transplanted murine heart.

    PubMed Central

    Lee, J. R.; Seok, C. J.; Kim, J. S.; Chang, J. M.; Seo, J. W.

    2001-01-01

    The heart transplantation-associated accelerated graft arteriosclerosis (AGAS) is one of the major causes of cardiac allograft failure. We investigated the early time-course of expresssion patterns of cytokines, transcription factor, and its inhibitor in the intraabdominally transplanted mice hearts that differed only in the D locus of class I histocompatibility antigen. The allograft hearts were harvested at 1-3, 5, 7, 14, 28, and 42 days after the transplantation, and the expressions of NF-kappaB/I-kappaB and cytokines (TNF-alpha, INF-gamma) were examined in these specimens. The expressions of TNF-alpha and INF-gamma were observed on day 1, peaking on day 5 and 7, respectively. Activated NF-kappaB (p65) expression was present on the cytoplasm and perinuclear area in the endothelial cells of coronary arteries on day 1. The peak of translocation of NF-B from cytoplasm to nucleus appeared on day 5 in the endothelial cells, myocytes, and leukocytes within the vessels, and remained elevated until day 42. The I-kappaB expression gradually increased from day 1 until day 5, but a remarkable decrease was detected on day 7. Our data suggest that the increased expressions of NF-kappaB/I-kappaB and cytokines (TNF-alpha, INF-gamma) play an important role in inducing immune responses in the donor allograft heart and hence the blockage of the expressions might be mandatory to avoid a potential graft failure. PMID:11511783

  14. Good Agreements Make Good Friends

    PubMed Central

    Han, The Anh; Pereira, Luís Moniz; Santos, Francisco C.; Lenaerts, Tom

    2013-01-01

    When starting a new collaborative endeavor, it pays to establish upfront how strongly your partner commits to the common goal and what compensation can be expected in case the collaboration is violated. Diverse examples in biological and social contexts have demonstrated the pervasiveness of making prior agreements on posterior compensations, suggesting that this behavior could have been shaped by natural selection. Here, we analyze the evolutionary relevance of such a commitment strategy and relate it to the costly punishment strategy, where no prior agreements are made. We show that when the cost of arranging a commitment deal lies within certain limits, substantial levels of cooperation can be achieved. Moreover, these levels are higher than that achieved by simple costly punishment, especially when one insists on sharing the arrangement cost. Not only do we show that good agreements make good friends, agreements based on shared costs result in even better outcomes. PMID:24045873

  15. Quick Guide: Power Purchase Agreements

    SciTech Connect

    2010-06-25

    Introduction to Federal power purchase agreements (PPAs), including available FEMP services and technical assistance as well as questions to ask when evaluating PPAs for a Federal renewable energy project.

  16. Empirical agreement in model validation.

    PubMed

    Jebeile, Julie; Barberousse, Anouk

    2016-04-01

    Empirical agreement is often used as an important criterion when assessing the validity of scientific models. However, it is by no means a sufficient criterion as a model can be so adjusted as to fit available data even though it is based on hypotheses whose plausibility is known to be questionable. Our aim in this paper is to investigate into the uses of empirical agreement within the process of model validation.

  17. Application Agreement and Integration Services

    NASA Technical Reports Server (NTRS)

    Driscoll, Kevin R.; Hall, Brendan; Schweiker, Kevin

    2013-01-01

    Application agreement and integration services are required by distributed, fault-tolerant, safety critical systems to assure required performance. An analysis of distributed and hierarchical agreement strategies are developed against the backdrop of observed agreement failures in fielded systems. The documented work was performed under NASA Task Order NNL10AB32T, Validation And Verification of Safety-Critical Integrated Distributed Systems Area 2. This document is intended to satisfy the requirements for deliverable 5.2.11 under Task 4.2.2.3. This report discusses the challenges of maintaining application agreement and integration services. A literature search is presented that documents previous work in the area of replica determinism. Sources of non-deterministic behavior are identified and examples are presented where system level agreement failed to be achieved. We then explore how TTEthernet services can be extended to supply some interesting application agreement frameworks. This document assumes that the reader is familiar with the TTEthernet protocol. The reader is advised to read the TTEthernet protocol standard [1] before reading this document. This document does not re-iterate the content of the standard.

  18. 7 CFR 247.4 - Agreements.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... CHILD NUTRITION PROGRAMS COMMODITY SUPPLEMENTAL FOOD PROGRAM § 247.4 Agreements. (a) What agreements are..., sex, or disability. (d) What is the duration of required agreements? Agreements between FNS and...

  19. 7 CFR 247.4 - Agreements.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... CHILD NUTRITION PROGRAMS COMMODITY SUPPLEMENTAL FOOD PROGRAM § 247.4 Agreements. (a) What agreements are..., sex, or disability. (d) What is the duration of required agreements? Agreements between FNS and...

  20. An adaptation of the Interpersonal Problem Areas Rating Scale: pilot and interrater agreement study

    PubMed Central

    de Andrade, Ana Claudia Fontes; Frank, Ellen; Neto, Francisco Lotufo; Houck, Patricia R

    2012-01-01

    Objective This article describes the adaptation of a rating scale of interpersonal psychotherapy problem areas to include a fifth problem area appropriate to bipolar disorder and an interrater agreement study in identifying interpersonal problem areas and selecting a primary treatment focus if patients were to engage in treatment. Method Five research interpersonal psychotherapists assessed nine audiotapes of a single interview with five bipolar and four unipolar patients in which the interpersonal inventory and identification of problem areas were undertaken. Results Raters agreed on presence and absence of problem areas in seven tapes. Kappas for identification of problem areas were 1.00 (grief), 0.77 (role dispute), 0.61 (role transition), 0.57 (interpersonal deficits) and 1.00 (loss of healthy self). Kappa for agreement on a primary clinical focus if patients were to engage in interpersonal psychotherapy treatment was 0.64. Conclusions The adaptation of the original scale to include an area pertinent to bipolar disorder proved to be applicable and relevant for use with this population. The results show substantial interrater agreement in identifying problem areas and potential treatment focus. PMID:19142412

  1. The new kappa-KTx 2.5 from the scorpion Opisthacanthus cayaporum.

    PubMed

    Camargos, Thalita Soares; Restano-Cassulini, Rita; Possani, Lourival Domingos; Peigneur, Steve; Tytgat, Jan; Schwartz, Carlos Alberto; Alves, Erica Maria C; de Freitas, Sonia Maria; Schwartz, Elisabeth Ferroni

    2011-07-01

    The kappa-KTx family of peptides, which is the newest K⁺-channel blocker family from scorpion venom, is present in scorpions from the families Scorpionidae and Liochelidae. Differently from the other scorpion KTx families, the three-dimensional structure of the known kappa-KTxs toxins is formed by two parallel α-helices linked by two disulfide bridges. Here, the characterization of a new kappa-KTx peptide, designated kappa-KTx 2.5, derived from the Liochelidae scorpion Opisthacanthus cayaporum, is described. This peptide was purified by HPLC and found to be identical to OcyC8, a predicted mature sequence precursor (UniProtKB C5J89) previously described by our group. The peptide was chemically synthesized and the circular dichroism (CD) spectra of both, native and synthetic, conducted at different temperatures in water and water/trifluoroethanol (TFE), showed a predominance of α-helices. The kappa-KTx 2.5 is heat stable and was shown to be a blocker of K⁺-currents on hKv1.1, and hKv1.4, with higher affinity for Kv1.4 channels (IC₅₀= 71 μM). Similarly to the other kappa-KTxs, the blockade of K⁺-channels occurred at micromolar concentrations, leading to uncertainness about their proper molecular target, and consequently their pharmacologic effect. In order to test other targets, kappa-KTx2.5 was tested on other K⁺-channels, on Na⁺-channels, on bacterial growth and on smooth muscle tissue, a known assay to identify possible bradykinin-potentiating peptides, due to the presence of two contiguous prolines at the C-terminal sequence. It has no effect on the targets used except on hKv1.1, and hKv1.4 expressed in Chinese hamster ovary cells. Since the only plausible function found for kappa-KTx2.5 seems to be the blockade of K⁺-channels, a discussion regarding the analysis of structure-function relationships is included in this communication, based on sequence alignments of members of the kappa-KTx toxin family, and on computational simulation of a

  2. Multiple mechanisms are implicated in the regulation of NF-kappa B activity during human cytomegalovirus infection.

    PubMed Central

    Kowalik, T F; Wing, B; Haskill, J S; Azizkhan, J C; Baldwin, A S; Huang, E S

    1993-01-01

    Infection-induced activation of the human cytomegalovirus major immediate early enhancer/promoter has been shown to be regulated primarily by transcription factor NF-kappa B cis elements. However, the mechanism(s) by which human cytomegalovirus induces NF-kappa B activity is unknown. A study was therefore undertaken to determine how this virus would affect normal NF-kappa B regulation. Viral infection of fibroblasts resulted in the specific stimulation of promoters containing major histocompatibility complex NF-kappa B cis elements fused upstream of the chloramphenicol acetyltransferase reporter gene. Electrophoretic mobility shift assays of nuclear extracts derived from mock- and virus-infected cells showed dramatic and sustained increases in DNA-binding proteins specific for these NF-kappa B sequences. Experiments using MAD-3 I kappa B, a specific inhibitor of NF-kappa B, and antibodies directed against rel family members demonstrated that the induced binding activities contained p50 and p65 proteins but not c-rel. Northern analysis indicated maximal levels of p50 mRNA by 4 h postinfection, whereas p65 and MAD-3 I kappa B mRNA accumulation peaked at 48-72 h postinfection, suggesting different regulatory mechanisms for p50 and p65/I kappa B genes. Electrophoretic mobility shift assays with deoxycholate-treated cytoplasmic extracts demonstrated a 3- to 4-fold decrease in the cytosolic stores of NF-kappa B binding activity by 4 h postinfection. Western blots probed with antibodies directed against MAD-3 I kappa B or pp40 (a protein isolated from chicken with sequence and biochemical properties similar to those of MAD-3 I kappa B) indicated that a cross-reactive peptide of 39 kDa was no longer detectable after 24 h postinfection. These results demonstrate that the activation and maintenance of nuclear NF-kappa B DNA binding and enhancer activities upon human cytomegalovirus infection occurs by multiple mechanisms. Images PMID:8381532

  3. Interobserver agreement for the spine instability neoplastic score varies according to the experience of the evaluator

    PubMed Central

    Teixeira, William Gemio Jacobsen; de Mesquita Coutinho, Pedro Ricardo; Marchese, Luiz Delboni; Narazaki, Douglas Kenji; Cristante, Alexandre Fogaça; Teixeira, Manoel Jacobsen; de Barros Filho, Tarcísio Eloy Pessoa; de Camargo, Olavo Pires

    2013-01-01

    OBJECTIVES: To evaluate the interobserver agreement for the Neoplastic Spine Instability Score (SINS) among spine surgeons with or without experience in vertebral metastasis treatment and physicians in other specialties. METHODS: Case descriptions were produced based on the medical records of 40 patients with vertebral metastases. The descriptions were then published online. Physicians were invited to evaluate the descriptions by answering questions according to the Neoplastic Spine Instability Score (SINS). The agreement among physicians was calculated using the kappa coefficient. RESULTS: Seventeen physicians agreed to participate: three highly experienced spine surgeons, seven less-experienced spine surgeons, three surgeons of other specialties, and four general practitioners (n = 17). The agreement for the final SINS score among all participants was fair, and it varied according to the SINS component. The agreement was substantial for the spine location only. The agreement was higher among experienced surgeons. The agreement was nearly perfect for spinal location among the spine surgeons who were highly experienced in vertebral metastases. CONCLUSIONS: This study demonstrates that the experience of the evaluator has an impact on SINS scale classification. The interobserver agreement was only fair among physicians who were not spine surgeons and among spine surgeons who were not experienced in the treatment of vertebral metastases, which may limit the use of the SINS scale for the screening of unstable lesions by less-experienced evaluators. PMID:23525318

  4. Gender agreement and multiple referents.

    PubMed

    Finocchiaro, Chiara; Mahon, Bradford Z; Caramazza, Alfonso

    2008-01-01

    We report a new pattern of usage in current, spoken Italian that has implications for both psycholinguistic models of language production and linguistic theories of language change. In Italian, gender agreement is mandatory for both singular and plural nouns. However, when two or more nouns of different grammatical gender appear in a conjoined noun phrase (NP), masculine plural agreement is required. In this study, we combined on-line and off-line methodologies in order to assess the mechanisms involved in gender marking in the context of multiple referents. The results of two pronoun production tasks showed that plural feminine agreement was significantly more difficult than plural masculine agreement. In a separate study using offline judgements of acceptability, we found that agreement violations in Italian are tolerated more readily in the case of feminine conjoined noun phrases (e.g., la mela e la banana 'the:fem apple:fem and the: fem banana: fem') than masculine conjoined noun phrases (e.g., il fiore e il libro 'the:mas flower: mas and the:mas book:mas'). Implications of these results are discussed both at the level of functional architecture within the language production system and at the level of changes in language use. PMID:21037930

  5. Gender agreement and multiple referents.

    PubMed

    Finocchiaro, Chiara; Mahon, Bradford Z; Caramazza, Alfonso

    2008-01-01

    We report a new pattern of usage in current, spoken Italian that has implications for both psycholinguistic models of language production and linguistic theories of language change. In Italian, gender agreement is mandatory for both singular and plural nouns. However, when two or more nouns of different grammatical gender appear in a conjoined noun phrase (NP), masculine plural agreement is required. In this study, we combined on-line and off-line methodologies in order to assess the mechanisms involved in gender marking in the context of multiple referents. The results of two pronoun production tasks showed that plural feminine agreement was significantly more difficult than plural masculine agreement. In a separate study using offline judgements of acceptability, we found that agreement violations in Italian are tolerated more readily in the case of feminine conjoined noun phrases (e.g., la mela e la banana 'the:fem apple:fem and the: fem banana: fem') than masculine conjoined noun phrases (e.g., il fiore e il libro 'the:mas flower: mas and the:mas book:mas'). Implications of these results are discussed both at the level of functional architecture within the language production system and at the level of changes in language use.

  6. Gender agreement and multiple referents

    PubMed Central

    Finocchiaro, Chiara; Mahon, Bradford Z.; Caramazza, Alfonso

    2010-01-01

    We report a new pattern of usage in current, spoken Italian that has implications for both psycholinguistic models of language production and linguistic theories of language change. In Italian, gender agreement is mandatory for both singular and plural nouns. However, when two or more nouns of different grammatical gender appear in a conjoined noun phrase (NP), masculine plural agreement is required. In this study, we combined on-line and off-line methodologies in order to assess the mechanisms involved in gender marking in the context of multiple referents. The results of two pronoun production tasks showed that plural feminine agreement was significantly more difficult than plural masculine agreement. In a separate study using offline judgements of acceptability, we found that agreement violations in Italian are tolerated more readily in the case of feminine conjoined noun phrases (e.g., la mela e la banana ‘the:fem apple:fem and the: fem banana: fem’) than masculine conjoined noun phrases (e.g., il fiore e il libro ‘the:mas flower: mas and the:mas book:mas’). Implications of these results are discussed both at the level of functional architecture within the language production system and at the level of changes in language use.* PMID:21037930

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

    PubMed Central

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

    2016-01-01

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

  8. Nrf2 regulates curcumin-induced aldose reductase expression indirectly via nuclear factor-kappaB.

    PubMed

    Kang, Eun Sil; Kim, Gil Hyeong; Kim, Hyo Jung; Woo, Im Sun; Ham, Sun Ah; Jin, Hana; Kim, Min Young; Kim, Hye Jung; Lee, Jae Heun; Chang, Ki Churl; Seo, Han Geuk; Hwang, Jin-Yong

    2008-07-01

    The osmotic response element (ORE) differs from the nuclear factor-kappaB (NF-kappaB) binding sequence by a single base pair; therefore, we investigated the involvement of NF-kappaB in the induction of aldose reductase (AR) by curcumin. Curcumin, an herb-derived polyphenolic compound, elicited an increase in the expression and promoter activity of the AR gene in a nuclear factor-erythroid 2-related factor 2 (Nrf2)-dependent manner. Small interfering RNA (siRNA) against p65 or BAY11-7082, an inhibitor of NF-kappaB, significantly suppressed the curcumin and/or Nrf2-induced increase in expression levels and promoter activity of the AR gene. BAY11-7082 or siRNA against p65 also attenuated the curcumin-induced increase in the promoter activity of the wild type AR-ORE(wt) gene, but not that of the mutated AR-ORE(mt), indicating that the ORE is essential for the response to NF-kappaB. The expression of p65, the promoter activity and DNA binding activity of NF-kappaB were enhanced in the presence of curcumin in cells that were transfected with Nrf2 compared to those treated with curcumin alone. Cells that had been preincubated with curcumin demonstrated resistance to reactive oxygen species-induced cell damage through the suppressive effects in the generation of reactive aldehydes. These effects were significantly attenuated in the presence of BAY11-7082, indicating the involvement of NF-kappaB in the cellular response of AR to oxidative stress and toxic aldehydes.

  9. From calcium to NF-kappa B signaling pathways in neurons.

    PubMed

    Lilienbaum, Alain; Israël, Alain

    2003-04-01

    NF-kappa B plays crucial roles in the nervous system, including potential roles in long-term responses to synaptic plasticity, pro- or antiapoptotic effects during developmental cell death, and neurodegenerative disorders. We report here the characterization of signaling pathways leading to the constitutive activation of NF-kappa B in primary cultures of neonatal cerebellar granule neurons, consecutive to calcium entry into the cytosol. We found that opening of calcium channels at the plasma membrane and at intracellular stores is indispensable for the basal NF-kappa B activity. We demonstrated further that three cellular sensors of the cytosolic Ca(2+) levels, calmodulin, protein kinases C (PKCs), and the p21(ras)/phosphatidylinositol 3-kinase (PI3K)/Akt pathway are simultaneously involved in the steps linking the Ca(2+) second messenger to NF-kappa B activity. Calmodulin triggers the activity of calcineurin, a phosphatase which plays a role in the basal NF-kappa B activity, while stimulation of both the calmodulin kinase II and Akt kinase pathways results in the up-regulation of the transcriptional potential of the p65 subunit of NF-kappa B. Finally, using pharmacological and molecular approaches, we analyze interactions between these three pathways at different levels and demonstrate a connection between PKCs and PI3K. All three components converge towards NF-kappa B, at the level of both nuclear translocation and transcriptional activity. These results stand in contrast to the situation in nonneuronal cells, which either do not respond to Ca(2+) or do not simultaneously activate all three cascades. By using a global approach in studying signaling pathways in neurons, these results provide further evidence to validate the concept of networks of transducing cascades, specific to cells and to physiological situations.

  10. Memory extinction entails the inhibition of the transcription factor NF-kappaB.

    PubMed

    Merlo, Emiliano; Romano, Arturo

    2008-01-01

    In contextual memories, an association between a positive or negative reinforcement and the contextual cues where the reinforcement occurs is formed. The re-exposure to the context without reinforcement can lead to memory extinction or reconsolidation, depending on the number of events or duration of a single event of context re-exposure. Extinction involves the temporary waning of the previously acquired conditioned response. The molecular processes underlying extinction and the mechanisms which determine if memory will reconsolidate or extinguish after retrieval are not well characterized, particularly the role of transcription factors and gene expression. Here we studied the participation of a transcription factor, NF-kappaB, in memory extinction. In the crab context-signal memory, the activation of NF-kappaB plays a critical role in consolidation and reconsolidation, memory processes that are well characterized in this model. The administration of a NF-kappaB inhibitor, sulfasalazine prior to extinction session impeded spontaneous recovery. Moreover, reinstatement experiments showed that the original memory was not affected and that NF-kappaB inhibition by sulfasalazine impaired spontaneous recovery strengthening the ongoing memory extinction process. Interestingly, in animals with fully consolidated memory, a brief re-exposure to the training context induced neuronal NF-kappaB activation and reconsolidation, while prolonged re-exposure induced NF-kappaB inhibition and memory extinction. These data constitutes a novel insight into the molecular mechanisms involved in the switch between memory reconsolidation and extinction. Moreover, we propose the inhibition of NF-kappaB as the engaged mechanism underlying extinction, supporting a novel approach for the pharmacological enhancement of this memory process. The accurate description of the molecular mechanisms that support memory extinction is potentially useful for developing new strategies and drug candidates

  11. Authenticated algorithms for Byzantine agreement

    SciTech Connect

    Dolev, D.; Strong, H.R.

    1983-11-01

    Reaching agreement in a distributed system in the presence of fault processors is a central issue for reliable computer systems. Using an authentication protocol, one can limit the undetected behavior of faulty processors to a simple failure to relay messages to all intended targets. In this paper the authors show that, in spite of such an ability to limit faulty behavior, and no matter what message types or protocols are allowed, reaching (Byzantine) agreement requires at least t+1 phases or rounds of information exchange, where t is an upper bound on the number of faulty processors. They present algorithms for reaching agreement based on authentication that require a total number of messages sent by correctly operating processors that is polynomial in both t and the number of processors, n. The best algorithm uses only t+1 phases and o(nt) messages. 9 references.

  12. A nuclear factor-kappaB inhibitor BAY 11-7082 suppresses endothelin-1 production in cultured vascular endothelial cells.

    PubMed

    Ohkita, Mamoru; Takaoka, Masanori; Shiota, Yasuko; Nojiri, Rumi; Sugii, Masato; Matsumura, Yasuo

    2002-05-01

    BAY 11-7082, an inhibitor of nuclear factor-kappaB (NF-kappaB), which prevents a step of the phosphorylation of inhibitory protein IkappaB bound to NF-kappaB, suppressed basal and tumor necrosis factor (TNF)-alpha-induced prepro endothelin (ET)-1 mRNA expression and NF-kappaB activation in cultured vascular endothelial cells. BAY 11-7082 significantly decreased basal and TNF-alpha-induced ET-1 release from endothelial cells. These results indicate that the inhibition of NF-kappaB activation contributes to the suppressive effect of BAY 11-7082 on ET-1 gene expression and ET-1 release, thereby suggesting that NF-kappaB plays an important role in the regulation of ET-1 production.

  13. Artemisolide is a typical inhibitor of I{kappa}B kinase {beta} targeting cysteine-179 residue and down-regulates NF-{kappa}B-dependent TNF-{alpha} expression in LPS-activated macrophages

    SciTech Connect

    Kim, Byung Hak; Lee, Jun-Young; Seo, Jee Hee; Lee, Hwa Young; Ryu, Shi Yong; Ahn, Byung Woo; Lee, Chong-Kil; Hwang, Bang Yeon; Han, Sang-Bae; Kim, Youngsoo

    2007-09-28

    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 of 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.

  14. Light chain editing in kappa-deficient animals: a potential mechanism of B cell tolerance

    PubMed Central

    1994-01-01

    The genetic organization of the kappa and lambda light chain loci permits multiple, successive rearrangement attempts at each allele. Multiple rearrangements allow autoreactive B cells to escape clonal deletion by editing their surface receptors. Editing may also facilitate efficient B cell production by salvaging cells with nonproductive light chain (L chain) rearrangements. To study receptor editing of kappa L chains, we have characterized B cells from mice hemizygous for the targeted inactivation of kappa (JCkD/wt) which have an anti-DNA heavy chain transgene, 3H9. Hybridomas from JCkD/wt mice exhibited an increased frequency of rearrangements to downstream Jk segments (such as Jk5) compared with most surveys from normal mice, consistent with receptor editing by sequential kappa locus rearrangements in JCkD/wt. We observed an even higher frequency of rearrangements to Jk5 in 3H9 JCkD/wt animals compared with nontransgenic JCkD/wt, consistent with editing of autoreactive kappa in 3H9 JCkD/wt. We also recovered a large number of 3H9 JCkD/wt lines with Vk12/13-Jk5 rearrangements and could demonstrate by PCR and Southern analysis that up to three quarters of these lines underwent multiple kappa rearrangements. To investigate editing at the lambda locus, we used homozygous kappa-deficient animals (JCkD/JCkD and 3H9 JCkD/JCkD). The frequencies of V lambda 1 and V lambda 2 rearrangements among splenic hybridomas in 3H9 JCkD/JCkD were reduced by 75% whereas V lambda X was increased 5-10-fold, compared with nontransgenic JCkD/JCkD animals. This indicates that V lambda 1 and V lambda 2 are negatively regulated in 3H9 JCkD/JCkD, consistent with earlier studies that showed that the 3H9 heavy chain, in combination with lambda 1 binds DNA. As successive lambda rearrangements to V lambda X do not inactivate V lambda 1, the consequence of lambda editing in 3H9 JCkD/JCkD would be failed allelic exclusion at lambda. However, analysis of 18 3H9 JCkD/JCkD hybridomas with V lambda 1

  15. Propagation of solitary waves in relativistic electron-positron-ion plasmas with kappa distributed electrons and positrons

    SciTech Connect

    Shah, Asif; Mahmood, S.; Haque, Q.

    2011-11-15

    Electrostatic ion acoustic solitary waves are studied in a plasma system comprising of relativistic ions, kappa distributed electrons, and positrons. The increase in the relativistic streaming factor and positron and electron kappa parameters cause the soliton amplitude to thrive. However, the soliton amplitude diminishes as the positron concentration is increased in the system. Our results are general and may be helpful, in understanding nonlinear phenomena in the presence of kappa distibuted electrons, positrons, and relativistically streaming ions.

  16. Inter- and Intra-observer Agreement of the Motion Palpation Test for Lumbar Vertebral Rotational Asymmetry

    PubMed Central

    Bracht, Marcelo Anderson; Celestino, Jardel; Schwertner, Debora Soccal; França, Leandro Cardoso; de Noronha, Marcos

    2015-01-01

    ABSTRACT Purpose: To investigate inter- and intra-observer agreement in the assessment of lumbar vertebral rotational (VR) asymmetry by a motion palpation test. Methods: For this prospective and descriptive test–retest study, 51 asymptomatic participants (40 women, 11 men; mean age 23.3 [SD 5.6] years) were recruited from the community. Each participant was assessed in two sessions by the same three observers, who assessed VR by means of a palpatory test for movement asymmetry. This test is performed by applying posteroanterior pressure in an alternating manner to the left and right transverse processes of a vertebra to determine motion asymmetry in the transverse plane and thus the vertebral position. Observers classified the vertebral position as neutral, rotation to the right, and rotation to the left; they were blinded to which participant was being assessed and to any previous results. Results: Intra- and inter-observer agreement was verified by the kappa coefficient (κ) and the weighted kappa coefficient (κw). Values of κ and κw varied from 0.07 (95% CI, −0.10 to 0.245) to 0.37 (95% CI, 0.11–0.63) for intra-observer agreement and from 0.12 (95% CI, −0.06 to 0.29) to 0.30 (95% CI, 0.08–0.52) for inter-observer agreement. Conclusion: The motion palpation test used to assess VR asymmetry has low agreement levels; therefore, its clinical significance for measuring vertebral position is questionable. PMID:25931669

  17. Agreement in self-reported personal risk factor information collected by different modes in Mongolia.

    PubMed

    Tserenpuntsag, B; Nelson, K; Lamjav, O; Triner, W; Smith, P; Kacica, M; McNutt, L-A

    2009-01-01

    This study compares two methods (a self-administered paper survey and a face-to-face interview) of collecting information about personal risk behaviours important for studies of HIV and other blood-borne pathogen transmissions in a developing country. In the framework of an epidemiological study conducted among 2504 donors in the Blood Center at the Ministry of Health, Mongolia, 2250 participants completed a short paper survey and 923 participants were interviewed concerning risk factors for hepatitis infections. A total of 669 individuals completed both surveys. McNemar's test and Kappa statistics were used to compare responses from both types of questionnaire. Kappa coefficients for health-care factors ranged from 0.57 (injection outside of hospital) to 0.81 (previous blood donation). Alcohol use and smoking were both reported more often in the interview than in the survey; the kappa coefficient was lowest (0.61) for alcohol use. While the prevalence of these behaviours depended on the mode of data collection, the association between behaviour and an outcome, hepatitis B surface antigen, was not substantially different between the two data collection methods. The results indicate that misclassification of risk behaviours is likely regardless of data collection method. However, in this study we found that biased estimates of prevalence likely did not substantially bias the estimates of association between risk factors and blood-borne infection. PMID:19103891

  18. Nuclear protein I{kappa}B-{zeta} inhibits the activity of STAT3

    SciTech Connect

    Wu, Zhihao; Zhang, Xiaoai; Yang, Juntao; Wu, Guangzhou; Zhang, Ying; Yuan, Yanzhi; Jin, Chaozhi; Chang, Zhijie; Wang, Jian; Yang, Xiaoming; He, Fuchu

    2009-09-18

    STAT3 (Signal transducer and activator of transcription 3) is a key transcription factor of the JAK-STAT (Janus kinase/signal transducer and activator of transcription) pathway that regulates cell proliferation and apoptosis. Activation of STAT3 is under tight regulation, and yet the different signaling pathways and the mechanisms that regulate its activity remain to be elucidated. Using a yeast two-hybrid screening, we have identified a nuclear protein I{kappa}B-{zeta} that interacts in a novel way with STAT3. This physical interaction was further confirmed by co-immunoprecipitation assays. The interaction regions were mapped to the coiled-coil domain of STAT3 and the C-terminal of I{kappa}B-{zeta}. Overexpression of I{kappa}B-{zeta} inhibited the transcriptional activity of STAT3. It also suppressed cell growth and induced cell apoptosis in SRC-simulated cells, which is partially mediated by down-regulation of expression of a known STAT3 target gene, MCL1. Our results suggest that I{kappa}B-{zeta} is a negative regulator of STAT3, and demonstrate a novel mechanism in which a component of the NF-{kappa}B signaling pathway inhibits the activation of STAT3.

  19. Motif module map reveals enforcement of aging by continual NF-kappaB activity.

    PubMed

    Adler, Adam S; Sinha, Saurabh; Kawahara, Tiara L A; Zhang, Jennifer Y; Segal, Eran; Chang, Howard Y

    2007-12-15

    Aging is characterized by specific alterations in gene expression, but their underlying mechanisms and functional consequences are not well understood. Here we develop a systematic approach to identify combinatorial cis-regulatory motifs that drive age-dependent gene expression across different tissues and organisms. Integrated analysis of 365 microarrays spanning nine tissue types predicted fourteen motifs as major regulators of age-dependent gene expression in human and mouse. The motif most strongly associated with aging was that of the transcription factor NF-kappaB. Inducible genetic blockade of NF-kappaB for 2 wk in the epidermis of chronologically aged mice reverted the tissue characteristics and global gene expression programs to those of young mice. Age-specific NF-kappaB blockade and orthogonal cell cycle interventions revealed that NF-kappaB controls cell cycle exit and gene expression signature of aging in parallel but not sequential pathways. These results identify a conserved network of regulatory pathways underlying mammalian aging and show that NF-kappaB is continually required to enforce many features of aging in a tissue-specific manner.

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

    SciTech Connect

    Hirose, Koichi; Wakashin, Hidefumi; Oki, Mie; Kagami, Shin-ichiro; Suto, Akira; Ikeda, Kei; Watanabe, Norihiko; Iwamoto, Itsuo; Furuichi, Yasuhiro; Nakajima, Hiroshi

    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 and 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.

  1. Genotyping of bovine kappa-casein loci following DNA sequence amplification.

    PubMed

    Fernando Medrano, J; Aguilar-Cordova, E

    1990-02-01

    Caseins are a family of milk proteins that exist in several molecular forms (alpha s1, alpha s2, beta and kappa) with variant alleles of each. Kappa-caseins (kappa-CN) exist as A or B variants and are of particular importance to the quality of the milk. We report a rapid non-radioactive method for differentiating bovine k-CN alleles. Unlike direct milk protein analysis, this method can be utilized for genotyping sperm, or animals of either sex at an early age. A 350bp fragment of the bovine kappa-CN gene was amplified by the polymerase chain reaction (PCR) technique. The amplified product digested with HinfI endonuclease generated restriction fragment length polymorphisms (RFLP's) that allowed precise identification of kappa-CN AA, AB or BB genotypes. Hybridization with allele specific oligo-probes confirmed the RFLP identification of genotypes. The accurate and early identification of milk protein genotypes can have a direct impact on dairy cattle breeding strategies.

  2. Vitamin D receptor negatively regulates bacterial-stimulated NF-kappaB activity in intestine.

    PubMed

    Wu, Shaoping; Liao, Anne P; Xia, Yinglin; Li, Yan Chun; Li, Jian-Dong; Sartor, R Balfour; Sun, Jun

    2010-08-01

    Vitamin D receptor (VDR) plays an essential role in gastrointestinal inflammation. Most investigations have focused on the immune response; however, how bacteria regulate VDR and how VDR modulates the nuclear factor (NF)-kappaB pathway in intestinal epithelial cells remain unexplored. This study investigated the effects of VDR ablation on NF-kappaB activation in intestinal epithelia and the role of enteric bacteria on VDR expression. We found that VDR(-/-) mice exhibited a pro-inflammatory bias. After Salmonella infection, VDR(-/-) mice had increased bacterial burden and mortality. Serum interleukin-6 in noninfected VDR(+/+) mice was undetectable, but was easily detectable in VDR(-/-) mice. NF-kappaB p65 formed a complex with VDR in noninfected wild-type mouse intestine. In contrast, deletion of VDR abolished VDR/P65 binding. P65 nuclear translocation occurred in colonic epithelial cells of untreated VDR(-/-) mice. VDR deletion also elevated NF-kappaB activity in intestinal epithelia. VDR was localized to the surface epithelia of germ-free mice, but to crypt epithelial cells in conventionalized mice. VDR expression, distribution, transcriptional activity, and target genes were regulated by Salmonella stimulation, independent of 1,25-dihydroxyvitamin D3. Our study demonstrates that commensal and pathogenic bacteria directly regulate colonic epithelial VDR expression and location in vivo. VDR negatively regulates bacterial-induced intestinal NF-kappaB activation and attenuates response to infection. Therefore, VDR is an important contributor to intestinal homeostasis and host protection from bacterial invasion and infection.

  3. Cellular redox status influences both cytotoxic and NF-kappa B activation in natural killer cells.

    PubMed Central

    Valle Blázquez, M; Luque, I; Collantes, E; Aranda, E; Solana, R; Peña, J; Muñoz, E

    1997-01-01

    The role of cellular redox status in both cytotoxic activity and NF-kappa B activation in natural killer (NK) cells was investigated. The results indicate that stimulation of NK cells, either freshly isolated from peripheral blood lymphocytes (PBL) or long-term cultured NK clones, with specific cell targets results in an increased binding activity of NF-kappa B and AP-1 transcription factors measured by gel retardation. Pretreatment of NK cells with the antioxidant pyrrolidine dithiocarbarmate (PDTC) leads to the inhibition of NF-kappa B activation but the AP-1 binding to DNA was superinduced. The inhibition of NF-kappa B by PDTC paralleled with an inhibition of spontaneous cytotoxicity mediated by NK cells. Moreover, the inhibitors of serine proteases, N-alpha-tosyl-L-lysine chloromethyl ketone and N-alpha-tosyl-L-phenylalanine chloromethyl ketone, also blocked the cytolytic activity of NK cells against the sensitive target K562. In contrast, NK activity was not affected by pretreatment of the effector cells with the proteasome inhibitor N-acetyl-leu-leu-norleucinal which selectively inhibits NF-kappa B activation. Altogether, these results support the hypothesis that the activation of NK cells involved transcriptional and post-transcriptional events, and that reactive intermediates may play an important role in the molecular processes related with the generation of a cytotoxic response by NK cells. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:9155655

  4. Insulin receptor substrate-3, interacting with Bcl-3, enhances p50 NF-{kappa}B activity

    SciTech Connect

    Kabuta, Tomohiro; Hakuno, Fumihiko; Cho, Yoshitake; Yamanaka, Daisuke; Chida, Kazuhiro; Asano, Tomoichiro; Wada, Keiji; Takahashi, Shin-Ichiro

    2010-04-09

    The insulin receptor substrate (IRS) proteins are major substrates of both insulin receptor and insulin-like growth factor (IGF)-I receptor tyrosine kinases. Previously, we reported that IRS-3 is localized to both cytosol and nucleus, and possesses transcriptional activity. In the present study, we identified Bcl-3 as a novel binding protein to IRS-3. Bcl-3 is a nuclear protein, which forms a complex with the homodimer of p50 NF-{kappa}B, leading to enhancement of transcription through p50 NF-{kappa}B. We found that Bcl-3 interacts with the pleckstrin homology domain and the phosphotyrosine binding domain of IRS-3, and that IRS-3 interacts with the ankyrin repeat domain of Bcl-3. In addition, IRS-3 augmented the binding activity of p50 to the NF-{kappa}B DNA binding site, as well as the tumor necrosis factor (TNF)-{alpha}-induced transcriptional activity of NF-{kappa}B. Lastly, IRS-3 enhanced NF-{kappa}B-dependent anti-apoptotic gene induction and consequently inhibited TNF-{alpha}-induced cell death. This series of results proposes a novel function for IRS-3 as a transcriptional regulator in TNF-{alpha} signaling, distinct from its function as a substrate of insulin/IGF receptor kinases.

  5. Inhibition of NF-kappa B by pyrrolidine dithiocarbamate blocks endothelial cell activation.

    PubMed

    Ferran, C; Millan, M T; Csizmadia, V; Cooper, J T; Brostjan, C; Bach, F H; Winkler, H

    1995-09-01

    Endothelial cell activation is achieved by the rapid, protein synthesis-independent induction of a characteristic set of genes. Because of the abundance of binding sites for the transcription factor NF-kappa B in the regulatory region of the aforementioned genes, we hypothesized that this factor might play a key role. Reactive oxygen intermediates act as second messengers in the activation of NF-kappa B. We have used the antioxidant pyrrolidine dithiocarbamate to analyze the effect of NF-kappa B inhibition on TNF alpha-induced EC activation in vitro. We show that pyrrolidine dithiocarbamate strongly reduces the TNF alpha-mediated induction of E-selectin, VCAM-1, ICAM-1, PAI-1, tissue factor, IL-8 and I kappa B-alpha. We present evidence identifying NF-kappa B as a central of EC activation. Therefore, this factor may represent a prime target for therapeutic intervention in pathologic conditions associated with EC activation such as allo- and xenograft rejection, atherosclerosis, ischemic reperfusion injury and vasculitis.

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

    SciTech Connect

    Togano, Tomiteru; Sasaki, Masataka; Watanabe, Mariko; Nakashima, Makoto; Tsuruo, Takashi; Umezawa, Kazuo; Higashihara, Masaaki; Watanabe, Toshiki; Horie, Ryouichi

    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 this 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.

  7. Articulation Agreements Ease the Way.

    ERIC Educational Resources Information Center

    Reese, Susan

    2002-01-01

    Articulation agreements between secondary and postsecondary institutions often provide for granting college credit for course work completed at another institution. They have been described as programs designed to create pathways of learning that ease the transition of students from secondary to postsecondary levels. (JOW)

  8. Block Transfer Agreement Evaluation Project

    ERIC Educational Resources Information Center

    Bastedo, Helena

    2010-01-01

    The objective of this project is to evaluate for the British Columbia Council on Admissions and Transfer (BCCAT) the effectiveness of block transfer agreements (BTAs) in the BC Transfer System and recommend steps to be taken to improve their effectiveness. Findings of this study revealed that institutions want to expand block credit transfer;…

  9. Allele frequencies of the major milk proteins in the Finnish Ayrshire and detection of a new kappa-casein variant.

    PubMed

    Ikonen, T; Ruottinen, O; Erhardt, G; Ojala, M

    1996-06-01

    A total of 20990 Finnish Ayrshire cows were phenotyped for the major milk proteins by isoelectric focusing in polyacrylamide gels. The predominant alleles in the Finnish Ayrshire were alpha S1-casein B (0.999), alpha S2-casein A (0.991), beta-casein A1 (0.509) and alpha 2 (0.490), kappa-casein A (0.612) and beta-lactoglobulin B (0.716). The kappa-casein E allele (0.307) was also rather common in the Finnish Ayrshire. A new kappa-casein variant (kappa-casein F) was demonstrated in two Finnish Ayrshire cows, a dam and a daughter.

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

    SciTech Connect

    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}B 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.

  11. The quantum harmonic oscillator on the sphere and the hyperbolic plane: {kappa}-dependent formalism, polar coordinates, and hypergeometric functions

    SciTech Connect

    Carinena, Jose F.; Ranada, Manuel F.; Santander, Mariano

    2007-10-15

    A nonlinear model representing the quantum harmonic oscillator on the sphere and the hyperbolic plane is solved in polar coordinates (r,{phi}) by making use of a curvature-dependent formalism. The curvature {kappa} is considered as a parameter and then the radial Schroedinger equation becomes a {kappa}-dependent Gauss hypergeometric equation. The energy spectrum and the wave functions are exactly obtained in both the sphere S{sup 2} ({kappa}>0) and the hyperbolic plane H{sup 2} ({kappa}<0). A comparative study between the spherical and the hyperbolic quantum results is presented.

  12. Polymorphism in {kappa}-(BEDT-TTF){sub 2}M(CF{sub 3}){sub 4}(solvent) superconductors

    SciTech Connect

    Geiser, U.; Schlueter, J.A.; Williams, J.M.; Kini, A.M.; Dudek, J.D.; Kelly, M.E.; Naumann, D.; Roy, T.

    1996-09-01

    A new crystallographic modification ({Kappa}{sub L}{sup `}) was found in the BEDT-TTF:M(CF{sub 3}){sub 4}{sup -}: solvent (M=Cu, Ag, Au) system. The structure of monoclinic {Kappa}{sub L}{sup `}-(BEDT- TTF){sub 2}Cu(CF{sub 3}){sub 4}(1,2-dibromo-1-chloroethane = DCBE) is reported. It differs from the orthorhombic {Kappa}{sub L}{sup `}- phase by having all BEDT-TTF molecules tilted in the same direction with respect to the conducting phase normal, whereas in {Kappa}{sub L} the tilt direction alternates between layers.

  13. Interobserver Agreement between On-Call Radiology Resident and General Radiologist Interpretations of CT Pulmonary Angiograms and CT Venograms

    PubMed Central

    Tamjeedi, Bahar; Correa, José; Semionov, Alexandre; Mesurolle, Benoît

    2015-01-01

    Objectives To evaluate the interobserver agreement (IOA) between the initial radiology resident and the final staff radiologist reports of combined computed tomographic pulmonary angiograms (CTPA) and computed tomographic venograms (CTV) performed during on-call hours. Materials and Methods Approval by the institutional review board was obtained. Six-hundred and ninety-six consecutive studies (CTPA or CTPA with CTV) performed during on-call hours and interpreted by 30 residents were identified. Radiology residents’ reports were compared to the final staff reports. Three tests outcomes were considered (positive, P; negative, N; indeterminate, I). Discordant cases were reviews by a chest radiologist. Results CTPAs were reported by staff radiologists as positive for pulmonary embolism (PE) in 18% (126/694), with a kappa of 0.81 (95% CI 0.77-0.86) with 3 outcomes (P, N, I), and a kappa of 0.89 (95% CI 0.85-0.94) with 2 outcomes (P, N). Regarding PE location, good concordance was observed for positive studies, with a kappa of 0.86 (95% CI 0.78 – 0.95). CTVs were reported as positive by staff radiologists in 8.5% (33/388), with a kappa of 0.66 (95% CI 0.55-0.77) with 3 outcomes (P, N, I), and a kappa of 0.89 (95% CI 0.8-1.0) with 2 outcomes (P, N). The IOA between residents and staff radiologists increased with increasing residency year level for CTPAs, but did not for CTVs. Conclusions Very good and good IOA were observed between resident and staff radiologist interpretations for CTPA and CTV, respectively, with tendency towards improved IOA as residency level of training increased for CTPA, but not for CTV. PMID:25938666

  14. 48 CFR 16.702 - Basic agreements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Basic agreements. 16.702... AND CONTRACT TYPES TYPES OF CONTRACTS Agreements 16.702 Basic agreements. (a) Description. A basic... attachment the required and applicable clauses agreed upon in the basic agreement. A basic agreement is not...

  15. 48 CFR 16.702 - Basic agreements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Basic agreements. 16.702... AND CONTRACT TYPES TYPES OF CONTRACTS Agreements 16.702 Basic agreements. (a) Description. A basic... attachment the required and applicable clauses agreed upon in the basic agreement. A basic agreement is not...

  16. 48 CFR 16.702 - Basic agreements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 1 2012-10-01 2012-10-01 false Basic agreements. 16.702... AND CONTRACT TYPES TYPES OF CONTRACTS Agreements 16.702 Basic agreements. (a) Description. A basic... attachment the required and applicable clauses agreed upon in the basic agreement. A basic agreement is not...

  17. 48 CFR 16.702 - Basic agreements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 1 2014-10-01 2014-10-01 false Basic agreements. 16.702... AND CONTRACT TYPES TYPES OF CONTRACTS Agreements 16.702 Basic agreements. (a) Description. A basic... attachment the required and applicable clauses agreed upon in the basic agreement. A basic agreement is not...

  18. 48 CFR 16.702 - Basic agreements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 1 2013-10-01 2013-10-01 false Basic agreements. 16.702... AND CONTRACT TYPES TYPES OF CONTRACTS Agreements 16.702 Basic agreements. (a) Description. A basic... attachment the required and applicable clauses agreed upon in the basic agreement. A basic agreement is not...

  19. Agreement on diagnoses of mental health problems between an online clinical assignment and a routine clinical assignment.

    PubMed

    Brøndbo, Per Håkan; Mathiassen, Børge; Martinussen, Monica; Handegård, Bjørn Helge; Kvernmo, Siv

    2013-02-01

    We examined the agreement between diagnoses assigned based on the Development and Well Being Assessment (DAWBA) information collected online, and ordinary day-to-day diagnostic assignment by Child and Adolescent Mental Health Service (CAMHS) clinicians. Diagnoses were compared for 286 patients. Raw agreement for diagnostic categories was 74-90%, resulting in kappa values of 0.41-0.49. Multinomial regression models for 'emotional diagnosis' and 'hyperkinetic/conduct diagnosis' were significant (P < 0.001). Age, gender and number of informants significantly contributed to the explanation of agreement and disagreement. Agreement on mental health diagnoses may be sufficient to replace routine clinical assignment of diagnoses with an online clinical assignment, thereby saving time and resources.

  20. [Agreement between two observers in the measurement of smoking and use of safety belt and cell phones in vehicles].

    PubMed

    Martínez-Sánchez, Jose M; Curto, Ariadna; Fernández, Esteve

    2012-01-01

    The aim of this study was to assess the feasibility of direct observations of smoking and use of seat belts and cell phones in drivers in the city of Barcelona, and to analyze the agreement between two observers. We performed 315 pairs of observations. The simple percentage inter-observer agreement between driver and passenger smoking was 100% with a Kappa coefficient=1.0. There was high inter-observer agreement in measurement of cell phone use and the number of passengers aged less than 14 years old. The variable with the lowest agreement was the driver's age. In conclusion, direct observation studies are a good resource for monitoring smoking and use of seat belts and cell phones in the drivers of motor vehicles.

  1. /sup 125/I-DPDYN, monoiodo (D-Pro10)- dynorphin (1-11), is an effective and useful tool for the study of kappa opioid receptors

    SciTech Connect

    Gairin, J.E.; Jomary, C.; Cros, J.; Meunier, J.C.

    1986-01-01

    Iodination of the kappa-selective peptide DPDYN, (D-Pro10)-dynorphin (1-11), has been performed. The non radioactive monoiodo derivative of DPDYN retains kappa-selectivity (kappa/mu = 48 and kappa/delta = 140), despite a general but moderate decrease in affinity. Radioiodination of DPDYN leads to the monoiodinated peptide (S.A 700-800 Ci/mmol) which interacts specifically and reversibly with the kappa-sites in guinea-pig cerebellum membranes with high affinity (KD = 0.12-0.18 nM). In guinea-pig brain (mu-delta-kappa) and rabbit cerebellum (kappa much less than mu), /sup 125/I-DPDYN discriminates between kappa- and other (mu, delta) binding sites. We have used this new labelled probe for the direct, precise and rapid (exposure time less than 100 hours) visualization of kappa-sites in guinea-pig and rabbit cerebellar slices using autoradiography.

  2. 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

    SciTech Connect

    Maier, Jana V.; Volz, Yvonne; Berger, Caroline; Schneider, Sandra; Cato, Andrew C.B.

    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 regulate 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.

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

    PubMed

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

    2015-08-01

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

  4. Association between alphas1-, beta- and kappa-casein loci in two Italian cattle breeds.

    PubMed

    Voglino, G F; Carignano

    1975-01-01

    The genetic polymorphism alphas1-, beta- and kappa-caseins was examined by gel electrophoresis in two Italian breeds, Valdostana and Piedmont. The results obtained from acid and basic migration show that the gene frequencies of the two breeds are very similar. Non independent assortment of genotypes among these milk protein loci was also studied. Results of analyses carried out on loci pairs showed that the genetic complex alphas1-CnB - beta-CnA2 was the most common in both breeds. In addition, the measure of linkage disequilibrium or gametic association (denoted delta) showed a close association between alphas1-Cn and beta-Cn, and between beta-Cn and kappa-Cn. No significant association was found between alphas1-Cn and kappa-Cn. This is in line with the model proposed by Grosclaude et al. (1973).

  5. The anisotropic jump equations for oblique fast shocks in a kappa distributed medium

    NASA Astrophysics Data System (ADS)

    Vogl, D. F.; Langmay, D.; Erkaev, N. V.; Biernat, H. K.; Farrugia, C. J.; Mühlbachler, S.

    2003-08-01

    In this paper, we concentrate on the solution of the anisotropic Rankine-Hugoniot equations for inclined fast shocks taking into account a new approach in closing the set of equations. In particular, the threshold conditions of the fire-hose and that of the mirror instability, obtained in a kinetic approach using the so-called kappa distribution function, are used to bound the range of the pressure anisotropy downstream of the discontinuity. We study the variation of the density across the shock for a given Alfvén Mach number and upstream pressure anisotropy and find that the parameter kappa is most sensitive to stable plasma conditions, i.e. low values of kappa reduce the pressure anisotropy downstream of the discontinuity.

  6. Hypothermia and poikilothermia induced by a kappa-agonist opioid and a neuroleptic.

    PubMed

    Adler, M W; Geller, E B

    1987-08-11

    When an opioid acting selectively at the kappa opioid receptor is administered subcutaneously to rats along with a neuroleptic at an ambient temperature of 20 degrees C a marked hypothermia ensues. The combination of U-50,488H (a kappa agonist) and chlorpromazine (a neuroleptic) caused a drop in body temperature amounting to as much as 11 degrees C, with all animals recovering after 24-48 h. Naloxone partially reversed the hypothermia. Similar, but less dramatic, decreases in body temperature occurred with other neuroleptics and weaker kappa agonists. The induction of poikilothermia was indicated when the body temperature approached the environment temperature and lethality resulted in 100% of the animals at ambient temperatures of 5 degrees C or 35 degrees C. The potential utility of this or similar combinations of drugs lies in such diverse applications as cardiac surgery, treatment of the near-drowning syndrome and space travel.

  7. Ion-acoustic supersolitons in plasmas with two-temperature electrons: Boltzmann and kappa distributions

    SciTech Connect

    Verheest, Frank; Hellberg, Manfred A.; Kourakis, Ioannis

    2013-08-15

    Acoustic supersolitons arise when a plasma model is able to support three consecutive local extrema of the Sagdeev pseudopotential between the undisturbed conditions and an accessible root. This leads to a characteristic electric field signature, where a simple bipolar shape is enriched by subsidiary maxima. Large-amplitude nonlinear acoustic modes are investigated, using a pseudopotential approach, for plasmas containing two-temperature electrons having Boltzmann or kappa distributions, in the presence of cold fluid ions. The existence domains for positive supersolitons are derived in a methodological way, both for structure velocities and amplitudes, in terms of plasma compositional parameters. In addition, typical pseudopotentials, soliton, and electric field profiles have been given to illustrate that positive supersolitons can be found in the whole range of electron distributions from Maxwellian to a very hard nonthermal spectrum in kappa. However, it is found that the parameter ranges that support supersolitons vary significantly over the wide range of kappa considered.

  8. Proinflammatory effects of pancreatic elastase are mediated through TLR4 and NF-kappaB.

    PubMed

    Hietaranta, Antti; Mustonen, Harri; Puolakkainen, Pauli; Haapiainen, Reijo; Kemppainen, Esko

    2004-10-01

    Pancreatic elastase has been implicated in the pathophysiology of severe acute pancreatitis, characterized by systemic inflammatory response, distant organ failure, and high mortality. Here we show that pancreatic elastase activates transcription factors NF-kappaB, AP-1, and NFAT in human myeloid cells (U-937 and THP-1) in culture. Pancreatic elastase also induces TNF-alpha secretion and increased expression of CD11b in THP-1 cells which can be inhibited by neutralizing anti-Toll-like receptor 4 (TLR4) antibodies. NF-kappaB blocking agents (MG-132, PGA1) prevented elastase-induced TNF-alpha secretion from THP-1 cells. Our results suggest that pancreatic elastase-induced proinflammatory effects are mediated by TLR4 and NF-kappaB in human myeloid cells.

  9. Alfven waves in dusty plasmas with plasma particles described by anisotropic kappa distributions

    SciTech Connect

    Galvao, R. A.; Ziebell, L. F.; Gaelzer, R.; Juli, M. C. de

    2012-12-15

    We utilize a kinetic description to study the dispersion relation of Alfven waves propagating parallelly to the ambient magnetic field in a dusty plasma, taking into account the fluctuation of the charge of the dust particles, which is due to inelastic collisions with electrons and ions. We consider a plasma in which the velocity distribution functions of the plasma particles are modelled as anisotropic kappa distributions, study the dispersion relation for several combinations of the parameters {kappa}{sub Parallel-To} and {kappa}{sub Up-Tack }, and emphasize the effect of the anisotropy of the distributions on the mode coupling which occurs in a dusty plasma, between waves in the branch of circularly polarized waves and waves in the whistler branch.

  10. Chemical synthesis and structure elucidation of bovine {kappa}-casein (1-44)

    SciTech Connect

    Bansal, Paramjit S.; Grieve, Paul A.; Marschke, Ronald J.; Daly, Norelle L.; McGhie, Emily; Craik, David J.; Alewood, Paul F. . E-mail: p.alewood@imb.uq.edu.au

    2006-02-24

    The caseins ({alpha}{sub s1}, {alpha}{sub s2}, {beta}, and {kappa}) are phosphoproteins present in bovine milk that have been studied for over a century and whose structures remain obscure. Here we describe the chemical synthesis and structure elucidation of the N-terminal segment (1-44) of bovine {kappa}-casein, the protein which maintains the micellar structure of the caseins. {kappa}-Casein (1-44) was synthesised by highly optimised Boc solid-phase peptide chemistry and characterised by mass spectrometry. Structure elucidation was carried out by circular dichroism and nuclear magnetic resonance spectroscopy. CD analysis demonstrated that the segment was ill defined in aqueous medium but in 30% trifluoroethanol it exhibited considerable helical structure. Further, NMR analysis showed the presence of a helical segment containing 26 residues which extends from Pro{sup 8} to Arg{sup 34}. This is First report which demonstrates extensive secondary structure within the casein class of proteins.

  11. Effects of the kappa opioid receptor antagonist MR-2266-BS on the acquisition of ethanol preference

    SciTech Connect

    Sandi, C.; Borrell, J.; Guaza, C. )

    1990-01-01

    Using a paradigm by which rats forced to drink a weak ethanol solution develop ethanol preference in consecutive retention testing days, the effects of the administration of the kappa opioid antagonist MR-2266-BS, prior to or after the forced ethanol session, were studied. Pre-conditioning subcutaneous (s.c.) administration of 1 mg/kg of MR-2266-BS induced a decrease in subsequent ethanol consumption without significantly modifying the acquisition of ethanol preference. Post-conditioning administration of MR-2266-BS induced both a dose-dependent reduction in ethanol consumption and in preference throughout the three following days. The results of the present study provide further support of the involvement of kappa-type opioids on drinking behavior, and suggest that kappa receptors may be involved in the consumption and development of preference to ethanol.

  12. Systemic kappaAL amyloidosis associated with bovine leukocyte adhesion deficiency.

    PubMed

    Taniyama, H; Yamamoto, S; Sako, T; Hirayama, K; Higuchi, H; Nagahata, H

    2000-01-01

    Histopathologic and immunohistochemical examinations were conducted on a 5-year-old Holstein-Friesian cow with systemic kappaAL amyloidosis associated with bovine leukocyte adhesion deficiency. Amyloid deposits were present in the perivascular and intercellular spaces of the visceral organs, such as the liver, kidneys, pancreas, adrenal glands, and upper alimentary tract. Amyloid was stained positively with Congo red with or without 5% potassium permanganate pretreatment and had green birefringence observed under polarized light. Immunohistochemically, amyloid reacted strongly against anti-bovine IgG (H+L) and anti-bovine kappa-light chain and reacted weakly against bovine X-light chain antibodies but was negative for anti-human amyloid AA antibody. This is the first description of AL amyloidosis immunohistochemically related to immunoglobulin kappa-light chains of precursor protein in cattle. PMID:10643989

  13. Automatic Kappa Angle Estimation for Air Photos Based on Phase Only Correlation

    NASA Astrophysics Data System (ADS)

    Xiong, Z.; Stanley, D.; Xin, Y.

    2016-06-01

    The approximate value of exterior orientation parameters is needed for air photo bundle adjustment. Usually the air borne GPS/IMU can provide the initial value for the camera position and attitude angle. However, in some cases, the camera's attitude angle is not available due to lack of IMU or other reasons. In this case, the kappa angle needs to be estimated for each photo before bundle adjustment. The kappa angle can be obtained from the Ground Control Points (GCPs) in the photo. Unfortunately it is not the case that enough GCPs are always available. In order to overcome this problem, an algorithm is developed to automatically estimate the kappa angle for air photos based on phase only correlation technique. This function has been embedded in PCI software. Extensive experiments show that this algorithm is fast, reliable, and stable.

  14. The Arabidopsis NIM1 protein shows homology to the mammalian transcription factor inhibitor I kappa B.

    PubMed Central

    Ryals, J; Weymann, K; Lawton, K; Friedrich, L; Ellis, D; Steiner, H Y; Johnson, J; Delaney, T P; Jesse, T; Vos, P; Uknes, S

    1997-01-01

    The NIM1 (for noninducible immunity) gene product is involved in the signal transduction cascade leading to both systemic acquired resistance (SAR) and gene-for-gene disease resistance in Arabidopsis. We have isolated and characterized five new alleles of nim1 that show a range of phenotypes from weakly impaired in chemically induced pathogenesis-related protein-1 gene expression and fungal resistance to very strongly blocked. We have isolated the NIM1 gene by using a map-based cloning procedure. Interestingly, the NIM1 protein shows sequence homology to the mammalian signal transduction factor I kappa B subclass alpha. NF-kappa B/I kappa B signaling pathways are implicated in disease resistance responses in a range of organisms from Drosophila to mammals, suggesting that the SAR signaling pathway in plants is representative of an ancient and ubiquitous defense mechanism in higher organisms. PMID:9090885

  15. Electrostatic Korteweg-deVries solitary waves in a plasma with Kappa-distributed electrons

    NASA Astrophysics Data System (ADS)

    Choi, C.-R.; Min, K.-W.; Rhee, T.-N.

    2011-09-01

    The Korteweg-deVries (KdV) equation that describes the evolution of nonlinear ion-acoustic solitary waves in plasmas with Kappa-distributed electrons is derived by using a reductive perturbation method in the small amplitude limit. We identified a dip-type (negative) electrostatic KdV solitary wave, in addition to the hump-type solution reported previously. The two types of solitary waves occupy different domains on the κ (Kappa index)-V (propagation velocity) plane, separated by a curve corresponding to singular solutions with infinite amplitudes. For a given Kappa value, the dip-type solitary wave propagates faster than the hump-type. It was also found that the hump-type solitary waves cannot propagate faster than V = 1.32.

  16. Cosmetic Plastic Surgery Statistics

    MedlinePlus

    2014 Cosmetic Plastic Surgery Statistics Cosmetic Procedure Trends 2014 Plastic Surgery Statistics Report Please credit the AMERICAN SOCIETY OF PLASTIC SURGEONS when citing statistical data or using ...

  17. In situ transmission infrared spectroscopy of high-kappa oxide atomic layer deposition onto silicon surfaces

    NASA Astrophysics Data System (ADS)

    Ho, Ming-Tsung

    Ultra-thin aluminum oxide (Al2O3) and hafnium oxide (HfO2) layers have been grown by atomic layer deposition (ALD) using tri-methyl-aluminum (TMA) and tetrakis-ethyl-methyl-amino-hafnium (TEMAH) respectively with heavy water (D2O) as the oxidizing agent. Several different silicon surfaces were used as substrates such as hydrogen terminated silicon (H/Si), SC2 (or RCA 2) cleaned native silicon oxide (SiO 2/Si), and silicon (oxy)nitride. In-situ transmission Fourier transform infrared spectroscopy (FTIR) has been adopted for the study of the growth mechanisms during ALD of these films. The vibrational spectra of gas phase TEMAH and its reaction byproducts with oxidants have also been investigated. Density functional theory (DFT) normal mode calculations show a good agreement with the experimental data when it is combined with linear wave-number scaling method and Fermi resonance mechanism. Ether (-C-O-C-) and tertiary alkylamine (N(R1R 2R3)) compounds are the two most dominant products of TEMAH reacting with oxygen gas and water. When ozone is used as the oxidant, gas phase CH2O, CH3NO2, CH3-N=C=O and other compounds containing -(C=O)- and --C-O-C- (or --O-C-) segments are observed. With substrate temperatures less than 400°C and 300°C for TMA and TEMAH respectively, Al oxide and Hf oxide ALD can be appropriately performed on silicon surfaces. Thin silicon (oxy)nitride thermally grown in ammonia on silicon substrate can significantly reduce silicon oxide interlayer formation during ALD and post-deposition annealing. The crystallization temperature of amorphous ALD grown HfO2 on nitridized silicon is 600°C, which is 100°C higher than on the other silicon surfaces. When HfO2 is grown on H/Si(111) at 100°C deposition temperature, minimum 5--10 ALD cycles are required for the full surface coverage. The steric effect can be seen by the evolution of the H-Si stretching mode at 2083 cm-1. The observed red shift of H-Si stretching to ˜ 2060 cm-1 can be caused by Si

  18. 78 FR 15951 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-13

    ... agreement. Agreement No.: 012196. Title: MSC/CSAV Ecuador--North Europe Vessel Sharing Agreement. Parties... on the U.S. East Coast on the one hand, and from ports on the U.S. East Coast to Panama and...

  19. 75 FR 11180 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-10

    ....gov . Agreement No.: 011730-003. Title: GWF/Dole Space Charter and Sailing Agreement. Parties: Dole... China-US Pacific Coast Two-Loop Space Charter, Sailing and Cooperative Working Agreement. Parties:...

  20. 40 CFR 35.1615 - Substate agreements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 CFR 33.240 (Intergovernmental agreements). A State may enter into an agreement with a substate... STATE AND LOCAL ASSISTANCE Cooperative Agreements for Protecting and Restoring Publicly Owned...

  1. 40 CFR 35.1615 - Substate agreements.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 CFR 33.240 (Intergovernmental agreements). A State may enter into an agreement with a substate... STATE AND LOCAL ASSISTANCE Cooperative Agreements for Protecting and Restoring Publicly Owned...

  2. 40 CFR 35.1615 - Substate agreements.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 CFR 33.240 (Intergovernmental agreements). A State may enter into an agreement with a substate... STATE AND LOCAL ASSISTANCE Cooperative Agreements for Protecting and Restoring Publicly Owned...

  3. 40 CFR 35.1615 - Substate agreements.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 CFR 33.240 (Intergovernmental agreements). A State may enter into an agreement with a substate... STATE AND LOCAL ASSISTANCE Cooperative Agreements for Protecting and Restoring Publicly Owned...

  4. 40 CFR 35.1615 - Substate agreements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 CFR 33.240 (Intergovernmental agreements). A State may enter into an agreement with a substate... STATE AND LOCAL ASSISTANCE Cooperative Agreements for Protecting and Restoring Publicly Owned...

  5. 77 FR 61751 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-11

    ... Agreement. Parties: Crowley Latin America Services, LLC and A.P. Moller-Maersk A/S Filing Party: Wayne R... . Agreement No.: 012155-001. Title: MSC/Zim South America East Coast Vessel Sharing Agreement....

  6. [Agreement between information from the Pregnant Card and the mother's memory of antenatal care].

    PubMed

    Santos Neto, Edson Theodoro dos; Leal, Maria do Carmo; Oliveira, Adauto Emmerich; Zandonade, Eliana; Gama, Silvana Granado Nogueira da

    2012-02-01

    This cross-sectional study aimed to verify agreement between information given by mothers after delivery and data recorded on Pregnant Cards about antenatal care under the Brazilian Unified National Health System in the Metropolitan Region of Vitória, Espírito Santo State, Brazil. The study considered a population of 1,035 postpartum mothers interviewed in eight hospitals, where the cards were copied. The representativeness of the sample was guaranteed by stratification according to the proportion of births. Kappa and McNemar tests were carried out with the collected and processed information. Agreement levels regarding antenatal care were predominantly poor (kappa < 0.20). Mothers tend to: overestimate the number of antenatal visits (McNemar = 51.73; p-value = 0.001); affirm diseases during pregnancy, such as diabetes, anemia, hypertension and urinary infections; report the performance of laboratory tests; report the carrying out of clinical examinations. Results suggest the need to reflect on the type of data used for planning and implementing maternal and child public health polices, since data varies depending on the information source. PMID:22331152

  7. Limiting technology by negotiated agreement

    SciTech Connect

    Carnesale, A.

    1983-01-01

    The author concentrates on anti-ballistic missile (ABM) systems as an example of a continuing effort to limit technology by negotiated agreement. He first discusses the ABM treaty of 1972, ratified by both the US and the USSR. Afterwards, he briefly treats each of the following: ballistic missile defense (BMD) dilemmas; nature of the BMD choice; technology; economics; deterrence; nuclear warfighting; relations with allies; arms control; Star Wars; and on limiting technology.

  8. Cytokine gene expression and activation of NF-{kappa}B in aniline-induced splenic toxicity

    SciTech Connect

    Wang Jianling; Kannan, Subburaj; Li Hui; Firoze Khan, M. . E-mail: mfkhan@utmb.edu

    2005-02-15

    Exposure to aniline results in selective toxicity to the spleen, leading to a variety of sarcomas on chronic exposure in rats, and fibrosis appears to be an important initiating preneoplastic lesion of the spleen. However, the molecular mechanism(s) by which aniline leads to fibrogenic response is not well understood. Previously, we have shown that aniline exposure leads to iron overload and induction of oxidative stress in the spleen. We hypothesized that aniline-induced oxidative stress in the spleen causes transcriptional up-regulation of fibrogenic cytokines via activation of redox-sensitive transcription factor, nuclear factor-kappa B (NF-{kappa}B). To test this hypothesis, male SD rats were treated with 0.5 mmol/kg/day aniline hydrochloride via drinking water for 30 days. Cytokine mRNAs were measured by real-time quantitative PCR, while cytokine release was determined in the supernatants of the cultured splenocytes using specific ELISAs. IL-1{alpha}, IL-6, and TNF-{alpha} mRNA levels showed 6.9-, 2.9-, and 2.6-fold increases, respectively, in the spleens of aniline-treated rats in comparison to the controls. The increases in mRNA levels were associated with enhanced secretion of these cytokines in the splenocyte culture supernatants. NF-{kappa}B p65 level in the nuclear extracts of cultured splenocytes of aniline-treated rats showed a 2-fold increase in comparison to the controls as quantitated by NF-{kappa}B p65-specific ELISA. The binding activity of NF-{kappa}B, determined by electrophoretic mobility shift assay (EMSA), also showed an increase in NF-{kappa}B binding in the nuclear extracts of the splenocytes from aniline-treated rats. The specificity of NF-{kappa}B binding was further confirmed by supershift assays. The results indicate that aniline exposure causes enhanced expression of IL-1{alpha}, IL-6, and TNF-{alpha}, both at mRNA and protein levels, suggesting their role in splenic fibrosis. Also, the increased NF-{kappa}B binding activity suggests

  9. Electron-ion collisional effect on Weibel instability in a Kappa distributed unmagnetized plasma

    SciTech Connect

    Kumar Kuri, Deep Das, Nilakshi

    2014-04-15

    Weibel instability has been investigated in the presence of electron-ion collisions by using standard Vlasov-Maxwell equations. The presence of suprathermal electrons has been included here by using Kappa distribution for the particles. The growth rate γ of Weibel instability has been calculated for different values of spectral index κ, collision frequency ν{sub ei}, and temperature anisotropy parameter β. A comparative study between plasma obeying Kappa distribution and that obeying Maxwellian distribution shows that the growth of instability is higher for the Maxwellian particles. However, in the presence of collisions, the suprathermal particles result in lower damping of Weibel mode.

  10. Adaptive evolution of relish, a Drosophila NF-kappaB/IkappaB protein.

    PubMed

    Begun, D J; Whitley, P

    2000-03-01

    NF-kappaB and IkappaB proteins have central roles in regulation of inflammation and innate immunity in mammals. Homologues of these proteins also play an important role in regulation of the Drosophila immune response. Here we present a molecular population genetic analysis of Relish, a Drosophila NF-kappaB/IkappaB protein, in Drosophila simulans and D. melanogaster. We find strong evidence for adaptive protein evolution in D. simulans, but not in D. melanogaster. The adaptive evolution appears to be restricted to the IkappaB domain. A possible explanation for these results is that Relish is a site of evolutionary conflict between flies and their microbial pathogens.

  11. Measurement Challenges in International Agreements

    NASA Astrophysics Data System (ADS)

    Luke, John

    2006-10-01

    Making measurements in support of international agreements can pose many challenges both from a policy and science point of view. Policy issues may arise because physics measurements made in the area of arms control or disarmament may be deemed too intrusive since they could possibly reveal sensitive information about the material that is being interrogated. Therefore, agreements must include a framework for safeguarding against the potential release of this information. Most of the scientific issues center around the fact that it is desirable to make high quality measurements without any operator interaction. This leads to the development of instrumentation and software that are very stable and robust. Due to different concerns, policy and science priorities may be at odds with one another. Therefore, it is the scientist's challenge - in this field - to keep policy makers informed by conveying what is technically possible and what is not in a manner that is easily understood and also negotiable. In this paper we will discuss some of the technology that has been developed to address some of these challenges in various international and model agreements. We will discuss the principle of informational barrier used in these measurement technologies to safeguard the release of sensitive information. We will also discuss some of the pitfalls that may arise when policy is ill informed about the physical constraints in the making of measurements of nuclear materials.

  12. 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

    SciTech Connect

    Kweon, Soo-Mi |; Wang, Beinan; Rixter, Davida; Lim, Jae Hyang; Koga, Tomoaki; Ishinaga, Hajime |; Chen, L.-F.; Jono, Hirofumi; Xu Haidong |; Li, J.-D. |. E-mail: Jian-Dong_Li@urmc.rochester.edu

    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 vitro 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.

  13. Functional limits of agreement: a method for assessing agreement between measurements of gait curves.

    PubMed

    Røislien, J; Rennie, L; Skaaret, I

    2012-07-01

    Three dimensional measurements of gait is a widely used tool in clinical gait analysis, and the evaluation of the reliability and reproducibility of the method is a recurring topic in the literature. The reliability of gait curve measurements is often assessed by extraction of single points from the gait curves before applying traditional reliability measures for scalars. This approach does, however, not explore the entire gait curves as continuous functions of time. In order to assess agreement between gait curves measured by different measurement methods, or measurers, we propose an extension of the concept of limits of agreement (LoA) to curve data. The LoA represent the estimated variation in the actual observations, which are then to be accompanied by an evaluation of whether this observed variation is within clinically acceptable limits. The generalization of the methodology from scalars to continuous function, e.g. gait curves, can be done using functional data analysis (FDA), a statistical methodology particularly developed for analyzing functional data. The resulting functional limits of agreement (FLoA) are continuous functions from 0 to 100% of the gait cycle, representing the difference in gait curves as measured by different measurement methods. The FLoA are presented in actual degrees for each joint and plane under study. The proposed methodology is demonstrated on real data from an inter-rater repeatability study. PMID:22727050

  14. Dose-rate effects of protons on in vivo activation of nuclear factor-kappa B and cytokines in mouse bone marrow cells

    SciTech Connect

    Rithidech, K.N.; Rusek, A.; Reungpatthanaphong, P.; Honikel, L.; Simon, S.R.

    2010-05-28

    The objective of this study was to determine the kinetics of nuclear factor-kappa B (NF-{kappa}B) activation and cytokine expression in bone marrow (BM) cells of exposed mice as a function of the dose rate of protons. The cytokines included in this study are pro-inflammatory [i.e., tumor necrosis factor-alpha (TNF-{alpha}), interleukin-1beta (IL-1{beta}), and IL-6] and anti-inflammatory cytokines (i.e., IL-4 and IL-10). We gave male BALB/cJ mice a whole-body exposure to 0 (sham-controls) or 1.0 Gy of 100 MeV protons, delivered at 5 or 10 mGy min{sup -1}, the dose and dose rates found during solar particle events in space. As a reference radiation, groups of mice were exposed to 0 (sham-controls) or 1 Gy of {sup 137}Cs {gamma} rays (10 mGy min{sup -1}). After irradiation, BM cells were collected at 1.5, 3, 24 h, and 1 month for analyses (five mice per treatment group per harvest time). The results indicated that the in vivo time course of effects induced by a single dose of 1 Gy of 100 MeV protons or {sup 137}Cs {gamma} rays, delivered at 10 mGy min{sup -1}, was similar. Although statistically significant levels of NF-{kappa}B activation and pro-inflammatory cytokines in BM cells of exposed mice when compared to those in the corresponding sham controls (Student's t-test, p < 0.05 or < 0.01) were induced by either dose rate, these levels varied over time for each protein. Further, only a dose rate of 5 mGy min{sup -1} induced significant levels of anti-inflammatory cytokines. The results indicate dose-rate effects of protons.

  15. Statistical physics and ecology

    NASA Astrophysics Data System (ADS)

    Volkov, Igor

    This work addresses the applications of the methods of statistical physics to problems in population ecology. A theoretical framework based on stochastic Markov processes for the unified neutral theory of biodiversity is presented and an analytical solution for the distribution of the relative species abundance distribution both in the large meta-community and in the small local community is obtained. It is shown that the framework of the current neutral theory in ecology can be easily generalized to incorporate symmetric density dependence. An analytically tractable model is studied that provides an accurate description of beta-diversity and exhibits novel scaling behavior that leads to links between ecological measures such as relative species abundance and the species area relationship. We develop a simple framework that incorporates the Janzen-Connell, dispersal and immigration effects and leads to a description of the distribution of relative species abundance, the equilibrium species richness, beta-diversity and the species area relationship, in good accord with data. Also it is shown that an ecosystem can be mapped into an unconventional statistical ensemble and is quite generally tuned in the vicinity of a phase transition where bio-diversity and the use of resources are optimized. We also perform a detailed study of the unconventional statistical ensemble, in which, unlike in physics, the total number of particles and the energy are not fixed but bounded. We show that the temperature and the chemical potential play a dual role: they determine the average energy and the population of the levels in the system and at the same time they act as an imbalance between the energy and population ceilings and the corresponding average values. Different types of statistics (Boltzmann, Bose-Einstein, Fermi-Dirac and one corresponding to the description of a simple ecosystem) are considered. In all cases, we show that the systems may undergo a first or a second order

  16. Effect of beta-casein, kappa-casein and beta-lactoglobulin genotypes on concentration of milk protein variants.

    PubMed

    Hallén, E; Wedholm, A; Andrén, A; Lundén, A

    2008-04-01

    Individual mid-lactation milk samples were collected from 116 cows of the Swedish Red and Swedish Holstein breeds with known genotypes of beta-casein, kappa-casein and beta-lactoglobulin. Detailed milk protein composition and allele-specific expression of beta-casein, kappa-casein and beta-lactoglobulin proteins in milk were analysed using reversed-phase high-performance liquid chromatography. Aggregate beta-/kappa-casein genotype was significantly associated with the kappa-casein concentration in milk. The lowest kappa-casein concentration was found in milk of cows with genotypes including kappa-casein E (A(1)A(2)/AE, A(1)A(1)/AE) and also A(2)A(2)/AA milk, whereas highest levels were associated with genotypes including kappa-casein B. Casein number was positively and concentration of beta-lactoglobulin negatively associated with the beta-lactoglobulin BB genotype. In heterozygote cows, beta-casein A(1) and beta-lactoglobulin A proteins were found at higher concentrations in milk compared with the protein variant encoded by the alternative allele at these loci, whereas kappa-casein A and B variants were found at similar concentrations in heterozygote AB cows.

  17. NF-kappaB is essential for the progression of KSHV- and EBV-infected lymphomas in vivo.

    PubMed

    Keller, Shannon A; Hernandez-Hopkins, Denise; Vider, Jelena; Ponomarev, Vladimir; Hyjek, Elizabeth; Schattner, Elaine J; Cesarman, Ethel

    2006-04-15

    Activated NF-kappaB is a critical mechanism by which lymphoma cells infected by Epstein-Barr virus (EBV/HHV-4) and Kaposi sarcoma herpesvirus (KSHV/HHV-8) are protected from apoptotic stress. Selective pharmacologic inhibition of constitutive NF-kappaB activity induces apoptosis in KSHV- and EBV-infected lymphoma cells. In both tumor types, pharmacologic inhibition of NF-kappaB in vitro induced identical mitochondrially mediated apoptosis cascades. Assessment of gene regulation by microarray analysis revealed that the inhibition of NF-kappaB in tumor cells results in the down-regulation of a distinct group of prosurvival genes, including cIAP-1, cIAP-2, cFLIP, and IL-6. Using EBV- and KSHV-associated lymphomas in a murine system, we demonstrated that Bay 11-7082, a selective pharmacologic inhibitor of NF-kappaB, prevents or delays tumor growth and prolongs disease-free survival. Inhibition of NF-kappaB activity and tumor growth responses were further documented using a traceable reporter KSHV-positive cell line and in vivo imaging. These findings indicate that specific NF-kappaB-regulated survival factors work cooperatively to protect KSHV- and EBV-infected lymphoma cells from apoptosis such that they promote the establishment and progression of KSHV- and EBV-associated lymphomas in mice. They also support the use of selective NF-kappaB inhibitors in the treatment of herpesvirus-associated lymphomas.

  18. Development of a cell death-based method for the screening of nuclear factor-kappaB inhibitors.

    PubMed

    Chopra, Puneet; Bajpai, Malini; Dastidar, Sunanda G; Ray, Abhijit

    2008-06-01

    Nuclear factor kappa B (NF-kappaB) plays a significant role in immunity and inflammation and represents a first choice as pharmacological target for anti-inflammatory therapy. However, research in this field has been hampered by the fact that no convenient assay suitable for large-scale screening procedures is available. The present study provides a cell death-based assay method for screening of nuclear factor-kappaB inhibitors. In this study, we observed that four distinct pharmacologic inhibitors of NF-kappaB, pyrrolidine dithiocarbamate (PDTC), N-tosyl-L-lysyl chloromethyl ketone (TPCK), genistein and BAY11-7082, resulted in the cell death of murine macrophages, J774A.1. DNA-binding experiments showed that lethal doses were consistent with those required for NF-kappaB inhibition. DNA fragmentation analysis showed that cell death is apoptotic in nature. Further studies suggested that NF-kappaB inhibitors induced apoptosis is independent of the involvement of other markers of cell death such as caspases and p38 MAP (Mitogen activated protein) kinase. From this study, we conclude that NF-kappaB activation may represent an important survival mechanism in macrophages. This study also provides a new cell-based screening method, as any compound that will inhibit NF-kappaB activity will result in the death of macrophages.

  19. Inhibition of lipopolysaccharide-stimulated NO production by crotafuran B in RAW 264.7 macrophages involves the blockade of NF-{kappa}B activation through the increase in I{kappa}B{alpha} synthesis

    SciTech Connect

    Lin, M.-W.; Tsao, L.-T.; Huang, L.-J.; Kuo, S.-C.; Weng, J.-R.; Ko, H.-H.; Lin, C.-N.; Lee, M.-R.; Wang, J.-P. . E-mail: w1994@vghtc.gov.tw

    2006-01-15

    Crotafuran B, a natural pterocarpanoid isolated from Crotalaria pallida, inhibited the lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production (IC{sub 5} 16.4 {+-} 0.7 {mu}M) and inducible nitric oxide synthase (iNOS) protein and mRNA expression (IC{sub 5} 11.5 {+-} 0.6 {mu}M and 11.8 {+-} 2.2 {mu}M, respectively), but not via its cytotoxicity or the inhibition of iNOS enzyme activity, in RAW 264.7 macrophages. Crotafuran B also reduced the iNOS promoter activity (IC{sub 5} 13.4 {+-} 0.1 {mu}M) in piNOS-LUC-transfected cells. Crotafuran B treatment inhibited the p65 nuclear translocation and the nuclear factor-{kappa}B (NF-{kappa}B) DNA binding activity in LPS-activated macrophages. Crotafuran B also reduced the NF-{kappa}B transcriptional activity in pNF-{kappa}B-LUC-transfected cells. Crotafuran B had no effect on the LPS-induced phosphorylation of inhibitory {kappa}B{alpha} (I{kappa}B{alpha}), but enhanced the cellular level of I{kappa}B{alpha} that rebounded to the basal levels and increased the I{kappa}B{alpha} mRNA expression. These results indicate that the crotafuran B inhibition of NO production involves a decrease in the iNOS gene expression via the inhibition of NF-{kappa}B activation through the increase in I{kappa}B{alpha} synthesis.

  20. Inter-Observer Agreement in Dysplasia Grading: Towards an Enhanced Gold Standard for Clinical Pathology Trials

    PubMed Central

    Speight, Paul M.; Abram, Timothy J.; Floriano, Pierre N.; James, Robert; Vick, Julie; Thornhill, Martin H.; Murdoch, Craig; Freeman, Christine; Hegarty, Anne M; D’Apice, Katy; Kerr, A. Ross; Phelan, Joan; Corby, Patricia; Khouly, Ismael; Vigneswaran, Nadarajah; Bouquot, Jerry; Demian, Nagi M.; Weinstock, Y. Etan; Redding, Spencer W.; Rowan, Stephanie; Yeh, Chih-Ko; McGuff, H. Stan; Miller, Frank R.; McDevitt, John T.

    2015-01-01

    Objective Inter-observer agreement in the context of oral epithelial dysplasia (OED) grading has been notoriously unreliable and can impose barriers for developing new molecular markers and diagnostic technologies. This paper aimed to report the details of a 3-stage histopathology review and adjudication process with the goal of achieving a consensus histopathologic diagnosis of each biopsy. Study Design Two adjacent serial histological sections of oral lesions from 846 patients were independently scored by two different pathologists from a pool of four. In instances where the original two pathologists disagreed, a third, independent adjudicating pathologist conducted a review of both sections. If a majority agreement was not achieved, the third stage involved a face-to-face consensus review. Results Individual pathologist pair kappa values ranged from 0.251 – 0.706 (fair – good) before the 3-stage review process During the initial review phase, the two pathologists agreed on a diagnosis for 69.9% of the cases. After the adjudication review by a third pathologist, an additional 22.8% of cases were given a consensus diagnosis (agreement of 2 out of 3 pathologists). Following the face-to-face review, the remaining 7.3% of cases had a consensus diagnosis. Conclusion The use of the defined protocol resulted in a substantial increase (30%) in diagnostic agreement and has the potential to improve the level of agreement for establishing gold standards for studies based on histopathologic diagnosis. PMID:26216170

  1. Observer agreement on pen level prevalence of clinical signs in finishing pigs.

    PubMed

    Petersen, Henrik Hagbard; Enøe, Claes; Nielsen, Elisabeth Okholm

    2004-07-16

    Four observers performed a standard clinical examination of finisher pigs in two commercial finisher herds. In herd 1,600 finisher pigs in 44 pens were examined. The observers assessed clinical signs of lameness, umbilical hernia and tail bite according to a standardized procedure. The prevalence of the clinical signs was estimated at the pen level. The procedure was repeated after 3 months in another herd, where 730 finisher pigs in 69 pens were examined. The agreement between observer pairs was assessed using prevalence-adjusted bias-adjusted kappa (PABAK) and proportionate-agreement estimates (Ppo) and Pneg). Observer bias was present despite training and standardization of the participating observers. The highest pen level agreement for the observer pairs was found for pens that had one or more pigs with tail bite (PABAK = 0.82-1.00) and umbilical hernia (PABAK = 0.77-1.00). The agreement was fair-to-moderate for identification of pens holding one or more lame pigs (PABAK = 0.27-0.7). In general, the average agreement of observer pairs on absence of clinical signs (Pneg) was higher than for presence (Ppos). The observer bias varied between observer pairs and with the clinical signs. PMID:15325769

  2. Effects of chronic food restriction on mu and kappa opioid binding in rat forebrain: a quantitative autoradiographic study.

    PubMed

    Wolinsky, T D; Carr, K D; Hiller, J M; Simon, E J

    1994-09-12

    It was previously observed that chronic food restriction lowers the threshold for lateral hypothalamic self-stimulation in a manner that is reversible by mu- and kappa-selective opioid antagonists. The present quantitative autoradiographic study was designed to investigate whether chronic food restriction alters regional mu and kappa opioid binding in brain. [3H]DAGO (mu) and mu/delta blocked [3H]BMZ (kappa) binding were analyzed in 34 brain regions from the medial prefrontal cortex to posterior hypothalamus. Significant reductions in mu binding were observed in caudal portions of the medial and lateral habenula, and the basolateral and basomedial nuclei of the amygdala. kappa binding was similarly reduced in medial habenula. Large increases in kappa binding were observed in the bed nucleus of the stria terminalis, ventral pallidum, and medial preoptic area. The possible involvement of these changes in the sensitization of reward by food restriction is discussed.

  3. The inhibitor of I kappa B alpha phosphorylation BAY 11-7082 prevents NMDA neurotoxicity in mouse hippocampal slices.

    PubMed

    Goffi, F; Boroni, F; Benarese, M; Sarnico, I; Benetti, A; Spano, P F; Pizzi, M

    2005-04-01

    NF-kappaB is a nuclear transcription factor involved in the control of fundamental cellular functions including cell survival. Among the many target genes of this factor, both pro- and anti-apoptotic genes have been described. To evaluate the contribution of NF-kappaB activation to excitotoxic insult, we analysed the effect of IkappaBalpha (IkappaBalpha) phosphorylation blockade on glutamate-induced toxicity in adult mouse hippocampal slices. By using immunocytochemical and EMSA techniques, we found that (i) acute exposure of hippocampal slices to NMDA induced nuclear translocation of NF-kappaB, (ii) NMDA-mediated activation of NF-kappaB was prevented by BAY 11-7082, an inhibitor of IkappaBalpha phosphorylation and degradation, and (iii) BAY 11-7082-mediated inhibition of NF-kappaB activation was associated with neuroprotection.

  4. 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

    1999-01-01

    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. PMID:9923611

  5. The Phi Delta Kappa At-Risk Scale: Its Composition, Meaning and Educational Implications.

    ERIC Educational Resources Information Center

    Freund, June; Lipka, Richard

    As part of a larger study by Phi Delta Kappa International (PDK), the PDK chapter in southeastern Kansas examined at-risk factors and "school effort" to address such factors in its geographical area. Data were obtained from the files of 270 "typical" students in Grades 4, 7, and 10 of three rural schools and from interviews with teachers,…

  6. Creating comparability among reliability coefficients: the case of Cronbach alpha and Cohen kappa.

    PubMed

    Becker, G

    2000-12-01

    Cronbach alpha and Cohen kappa were compared and found to differ along two major facets. A fourfold classification system based on these facets clarifies the double contrast and produces a common metric allowing direct comparability. A new estimator, coefficient beta, is introduced in the process and is presented as a complement to coefficient alpha in estimating the psychometric properties of test scores and ratings.

  7. Ion-acoustic cnoidal waves in plasmas with warm ions and kappa distributed electrons and positrons

    SciTech Connect

    Kaladze, T.; Mahmood, S.

    2014-03-15

    Electrostatic ion-acoustic periodic (cnoidal) waves and solitons in unmagnetized electron-positron-ion (EPI) plasmas with warm ions and kappa distributed electrons and positrons are investigated. Using the reductive perturbation method, the Korteweg-de Vries (KdV) equation is derived with appropriate boundary conditions for periodic waves. The corresponding analytical and various numerical solutions are presented with Sagdeev potential approach. Differences between the results caused by the kappa and Maxwell distributions are emphasized. It is revealed that only hump (compressive) structures of the cnoidal waves and solitons are formed. It is shown that amplitudes of the cnoidal waves and solitons are reduced in an EPI plasma case in comparison with the ordinary electron-ion plasmas. The effects caused by the temperature variations of the warm ions are also discussed. It is obtained that the amplitude of the cnoidal waves and solitons decreases for a kappa distributed (nonthermal) electrons and positrons plasma case in comparison with the Maxwellian distributed (thermal) electrons and positrons EPI plasmas. The existence of kappa distributed particles leads to decreasing of ion-acoustic frequency up to thermal ions frequency.

  8. Transfection of an immunoglobulin kappa gene into mature human B lymphocytes

    SciTech Connect

    Bich-Thuy, L.T.; Queen, C.

    1988-01-01

    The authors show in this report that the transcription induced by interleukin-2 or pokeweed mitogens of the kappa MOPC 41 immunoglobulin light-chain gene transfected into primary human or murine B lymphocytes initiates from a previously unobserved start site about 26 base pairs upstream of the start site used in myeloma cell lines.

  9. Role of Human DNA Polymerase kappa in Extension Opposite from a cis-syn Thymine Dimer

    SciTech Connect

    R Vasquez-Del Carpio; T Silverstein; S Lone; R Johnson; L Prakash; S Prakash; A Aggarwal

    2011-12-31

    Exposure of DNA to UV radiation causes covalent linkages between adjacent pyrimidines. The most common lesion found in DNA from these UV-induced linkages is the cis-syn cyclobutane pyrimidine dimer. Human DNA polymerase {Kappa} (Pol{Kappa}), a member of the Y-family of DNA polymerases, is unable to insert nucleotides opposite the 3'T of a cis-syn T-T dimer, but it can efficiently extend from a nucleotide inserted opposite the 3'T of the dimer by another DNA polymerase. We present here the structure of human Pol{Kappa} in the act of inserting a nucleotide opposite the 5'T of the cis-syn T-T dimer. The structure reveals a constrained active-site cleft that is unable to accommodate the 3'T of a cis-syn T-T dimer but is remarkably well adapted to accommodate the 5'T via Watson-Crick base pairing, in accord with a proposed role for Pol{Kappa} in the extension reaction opposite from cyclobutane pyrimidine dimers in vivo.

  10. Evaluation of an Imputed Pitch Velocity Model of the Auditory Kappa Effect

    ERIC Educational Resources Information Center

    Henry, Molly J.; McAuley, J. Devin

    2009-01-01

    Three experiments evaluated an imputed pitch velocity model of the auditory kappa effect. Listeners heard 3-tone sequences and judged the timing of the middle (target) tone relative to the timing of the 1st and 3rd (bounding) tones. Experiment 1 held pitch constant but varied the time (T) interval between bounding tones (T = 728, 1,000, or 1,600…

  11. kappa opioid receptors in human microglia downregulate human immunodeficiency virus 1 expression.

    PubMed Central

    Chao, C C; Gekker, G; Hu, S; Sheng, W S; Shark, K B; Bu, D F; Archer, S; Bidlack, J M; Peterson, P K

    1996-01-01

    Microglial cells, the resident macrophages of the brain, play an important role in the neuropathogenesis of human immunodeficiency virus type 1 (HIV-1), and recent studies suggest that opioid peptides regulate the function of macrophages from somatic tissues. We report herein the presence of kappa opioid receptors (KORs) in human fetal microglia and inhibition of HIV-1 expression in acutely infected microglial cell cultures treated with KOR ligands. Using reverse transcriptase-polymerase chain reaction and sequencing analyses, we found that mRNA for the KOR was constitutively expressed in microglia and determined that the nucleotide sequence of the open reading frame was identical to that of the human brain KOR gene. The expression of KOR in microglial cells was confirmed by membrane binding of [3H]U69,593, a kappa-selective ligand, and by indirect immunofluorescence. Treatment of microglial cell cultures with U50,488 or U69,593 resulted in a dose-dependent inhibition of expression of the monocytotropic HIV-1 SF162 strain. This antiviral effect of the kappa ligands was blocked by the specific KOR antagonist, nor-binaltrophimine. These findings suggest that kappa opioid agonists have immunomodulatory activity in the brain, and that these compounds could have potential in the treatment of HIV-1-associated encephalopathy. Images Fig. 2 Fig. 4 PMID:8755601

  12. Molecular cloning and expression of bovine kappa-casein in Escherichia coli

    SciTech Connect

    Kang, Y.C.; Richardson, T.

    1988-01-01

    A cDNA library was constructed using poly(A)/sup +/RNA from bovine mammary gland. This cDNA library of 6000 clones was screened employing colony hybridization using /sup 32/P-labelled oligonucleotide probes and restriction endonuclease mapping. The cDNA from the selected plasmid, pKR76, was sequenced using the dideoxy-chain termination method. The cDNA insert of pKR76 carries the full-length sequence, which codes for mature kappa-casein protein. The amino acid sequence deduced from the cDNA sequence fits the published amino acid sequence with three exceptions; the reported pyroglutamic acid at position 1, tyrosine at position 35, and aspartic acid at position 81 are, respectively, a glutamine, a histidine, and an asparagine in the clone containing pKR76. The MspI-, NlaIV-cleaved fragment (630 base pair) from the kappa-casein cDNA insert has been subcloned into expression vectors pUC18 and pKK233-2, which contain a lac promoter and a trc promoter, respectively. Escherichia coli cells carrying the recombinant expression plasmids were shown to produce kappa-casein protein having the expected mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and being recognized by specific antibodies raised against natural bovine kappa-casein.

  13. Anti-psoriatic drug anthralin activates transcription factor NF-kappa B in murine keratinocytes.

    PubMed

    Schmidt, K N; Podda, M; Packer, L; Baeuerle, P A

    1996-06-01

    Anthralin is one of the most effective and safest therapeutic agents for the treatment of psoriasis, a skin disease characterized by epidermal hyperproliferation and hyperkeratosis. The drug induces and inflammatory response in the skin involving the expression of cytokine and cell adhesion molecule genes that is thought to be essential for its therapeutic efficacy. Reactive oxygen intermediates (ROIs) generated in vivo during the auto-oxidation of anthralin were discussed as mediators of the inflammatory response, but it is not yet understood how this is translated into novel inflammatory gene expression. In this study, we show that at little as 10 microM anthralin can activate a prototypic form of transcription factor NF-(kappa)B, a central transcriptional regulator of inflammatory and immune responses. Two different lines of evidence show that ROIs, in particular H2O2, are second messengers for the anthralin-induced NF-(kappa)B activation. Firstly, the activation could be inhibited by the structurally unrelated antioxidants N-acetyl-L-cysteine and pyrrolidinedithiocarbamate. Secondly, keratinocytes stably overexpressing catalase showed a significant reduction of NF-(kappa)B activation, while stable overexpression of Cu/Zn-superoxide dismutase augmented the anthralin effect. Our data suggest that ROI-induced NF-(kappa)B plays a role in the anti-psoriatic activity of the drug anthralin.

  14. Ion firehose instability in plasmas with plasma particles described by product bi-kappa distributions

    SciTech Connect

    Santos, M. S. dos; Ziebell, L. F. Gaelzer, R.

    2014-11-15

    We investigate the dispersion relation for low frequency electromagnetic waves propagating parallel to the ambient magnetic field, considering that the velocity distributions of ions and electrons can be either bi-Maxwellian of product bi-kappa distributions. The effect of the anisotropy and non-thermal features associated to the product-bi-kappa distributions on the firehose instability are numerically investigated. The general conclusion to be drawn from the results obtained is that the increase in non-thermal features which is consequence of the decrease of the κ indexes in the ion distribution contributes to increase the instability in magnitude and wave number range, in comparison with bi-Maxwellian distributions with similar temperature anisotropy, and that the increase of non-thermal features in the electron distribution contributes to the quenching of the instability, which is nevertheless driven by the anisotropy in the ion distribution. Significant differences between results obtained either considering product-bi-kappa distributions or bi-kappa distributions are also reported.

  15. Kappa Opioid Receptors Mediate where Fear Is Expressed Following Extinction Training

    ERIC Educational Resources Information Center

    Cole, Sindy; Richardson, Rick; McNally, Gavan P.

    2011-01-01

    Six experiments used a within-subjects renewal design to examine the involvement of kappa opioid receptors (KORs) in regulating the expression and recovery of extinguished fear. Rats were trained to fear a tone conditioned stimulus (CS) via pairings with foot shock in a distinctive context (A). This was followed by extinction training of the CS in…

  16. In-situ observation of electron kappa distributions associated with discrete auroral arcs

    NASA Astrophysics Data System (ADS)

    Ogasawara, Keiichi; Livadiotis, George; Samara, Marilia; Michell, Robert; Grubbs, Guy

    2016-04-01

    The Medium-energy Electron SPectrometer (MESP) sensor aboard a NASA sounding rocket was launched from Poker Flat Research Range on 3 March 2014 as a part of Ground-to-Rocket Electrodynamics-Electrons Correlative Experiment (GREECE) mission. GREECE targeted to discover convergent E-field structures at low altitude ionosphere to find their contribution to the rapid fluid-like structures of aurora, and MESP successfully measured the precipitating electrons from 2 to 200 keV within multiple discrete auroral arcs with the apogee of 350 km. MESP's unprecedented electron energy acceptance and high geometric factor made it possible to investigate precise populations of the suprathermal components measured in the inverted-V type electron energy distributions. The feature of these suprathermal electrons are explained by the kappa distribution functions with the parameters (densty, temperature, and kappa) consistent with the near-Earth tail plasma sheet, suggesting the source population of the auroral electrons. The kappa-values are different between each arc observed as a function of latitude, but are almost stable within one discrete arc. We suggest that this transition of kappa reflects the probagation history of source electrons through the plasma sheet by changing its state from non-equilibrium electron distributions to thermal ones.

  17. Direct determination of flat-band voltage for metal/high {kappa} oxide/semiconductor heterointerfaces by electric-field-induced second-harmonic generation

    SciTech Connect

    Chang, C.-L.; Lee, W. C.; Chu, L. K.; Hong, M.; Kwo, J.; Chang, Y.-M.

    2011-04-25

    We have employed electric-field-induced second-harmonic (EFISH) generation to determine the flat-band voltage (V{sub FB}) of Cr/ALD-Al{sub 2}O{sub 3}/MBE-HfO{sub 2}/n-Si (001) MOS structure. Due to the phase sensitivity of EFISH signal to the electric field in the space charge region, the V{sub FB} of -1.20{+-}0.07 V was determined by analyzing the relative phase change in the EFISH signal as a function of the applied gate voltage. The obtained value is in good agreement with that estimated by the capacitance-voltage measurement. This study demonstrated an all-optical technique to directly determine the flat-band voltage for the high {kappa} oxide/Si heterointerfaces.

  18. 32 CFR 78.7 - Standard agreement.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false Standard agreement. 78.7 Section 78.7 National... VOLUNTARY STATE TAX WITHHOLDING FROM RETIRED PAY § 78.7 Standard agreement. Standard Agreement For Voluntary..., hereafter referred to as the “Standard Agreement,” establishes administrative procedures and...

  19. 48 CFR 3416.702 - Basic agreements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Basic agreements. 3416.702... CONTRACTING METHODS AND CONTRACT TYPES TYPES OF CONTRACTS Agreements 3416.702 Basic agreements. (a)-(d) (e) Negotiated overhead rates. Basic agreements may include negotiated overhead rates for...

  20. 78 FR 26779 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-08

    ... reflects the suspension of the agreement, effective May 1, 2013 through April 14, 2015. Agreement No... the fact that the parties have agreed to charter and rationalize vessel space among themselves and...). Agreement No.: 012206. Title: Industria Armamento Meridionale S.P.A./K-Line Space Charter Agreement....

  1. 2 CFR 182.620 - Cooperative agreement.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... agreement. Cooperative agreement means an award of financial assistance that, consistent with 31 U.S.C. 6305... development agreements as defined in 15 U.S.C. 3710a. ... MANAGEMENT AND BUDGET GOVERNMENTWIDE GUIDANCE FOR GRANTS AND AGREEMENTS NATIONAL POLICY...

  2. 5 CFR 2421.20 - Election agreement.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Election agreement. 2421.20 Section 2421... Election agreement. Election agreement means an agreement under part 2422 of this subchapter signed by all... representation election in an appropriate unit....

  3. 5 CFR 2421.20 - Election agreement.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 5 Administrative Personnel 3 2012-01-01 2012-01-01 false Election agreement. 2421.20 Section 2421... Election agreement. Election agreement means an agreement under part 2422 of this subchapter signed by all... representation election in an appropriate unit....

  4. 5 CFR 2421.20 - Election agreement.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 3 2011-01-01 2011-01-01 false Election agreement. 2421.20 Section 2421... Election agreement. Election agreement means an agreement under part 2422 of this subchapter signed by all... representation election in an appropriate unit....

  5. 5 CFR 2421.20 - Election agreement.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 5 Administrative Personnel 3 2014-01-01 2014-01-01 false Election agreement. 2421.20 Section 2421... Election agreement. Election agreement means an agreement under part 2422 of this subchapter signed by all... representation election in an appropriate unit....

  6. 5 CFR 2421.20 - Election agreement.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 3 2013-01-01 2013-01-01 false Election agreement. 2421.20 Section 2421... Election agreement. Election agreement means an agreement under part 2422 of this subchapter signed by all... representation election in an appropriate unit....

  7. 7 CFR 1948.98 - Grant agreements.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 13 2013-01-01 2013-01-01 false Grant agreements. 1948.98 Section 1948.98 Agriculture... § 1948.98 Grant agreements. The following Grant Agreements are a part of this regulation. (a) Exhibit A of this subpart is a Grant Agreement for Growth Management and Housing Planning Grants for...

  8. 7 CFR 1948.98 - Grant agreements.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 13 2011-01-01 2009-01-01 true Grant agreements. 1948.98 Section 1948.98 Agriculture... § 1948.98 Grant agreements. The following Grant Agreements are a part of this regulation. (a) Exhibit A of this subpart is a Grant Agreement for Growth Management and Housing Planning Grants for...

  9. 7 CFR 1415.11 - Restoration agreements.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Restoration agreements. 1415.11 Section 1415.11... Restoration agreements. (a) Restoration agreements are only authorized to be used in conjunction with... a restoration agreement is needed. Such a determination is also subject to the availability...

  10. 7 CFR 1415.11 - Restoration agreements.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Restoration agreements. 1415.11 Section 1415.11... Restoration agreements. (a) Restoration agreements are only authorized to be used in conjunction with... a restoration agreement is needed. Such a determination is also subject to the availability...

  11. 7 CFR 947.111 - Marketing agreement.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Marketing agreement. 947.111 Section 947.111 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing... Definitions § 947.111 Marketing agreement. Marketing agreement means Marketing Agreement No. 114, as amended....

  12. 7 CFR 947.111 - Marketing agreement.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Marketing agreement. 947.111 Section 947.111 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing... Definitions § 947.111 Marketing agreement. Marketing agreement means Marketing Agreement No. 114, as amended....

  13. 46 CFR 356.41 - Management agreements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 8 2010-10-01 2010-10-01 false Management agreements. 356.41 Section 356.41 Shipping..., Management Agreements and Exclusive or Long-Term Contracts § 356.41 Management agreements. (a) An owner or bareboat charterer of a Fishing Industry Vessel may enter into a management agreement with a Non-Citizen...

  14. 25 CFR 163.71 - Agreement funding.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false Agreement funding. 163.71 Section 163.71 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER GENERAL FORESTRY REGULATIONS Cooperative Agreements § 163.71 Agreement funding. In cooperative agreements, the Secretary is authorized to advance...

  15. 25 CFR 163.71 - Agreement funding.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Agreement funding. 163.71 Section 163.71 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER GENERAL FORESTRY REGULATIONS Cooperative Agreements § 163.71 Agreement funding. In cooperative agreements, the Secretary is authorized to advance...

  16. 25 CFR 163.71 - Agreement funding.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 1 2011-04-01 2011-04-01 false Agreement funding. 163.71 Section 163.71 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER GENERAL FORESTRY REGULATIONS Cooperative Agreements § 163.71 Agreement funding. In cooperative agreements, the Secretary is authorized to advance...

  17. 25 CFR 163.71 - Agreement funding.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 1 2013-04-01 2013-04-01 false Agreement funding. 163.71 Section 163.71 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER GENERAL FORESTRY REGULATIONS Cooperative Agreements § 163.71 Agreement funding. In cooperative agreements, the Secretary is authorized to advance...

  18. 25 CFR 163.71 - Agreement funding.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 1 2012-04-01 2011-04-01 true Agreement funding. 163.71 Section 163.71 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER GENERAL FORESTRY REGULATIONS Cooperative Agreements § 163.71 Agreement funding. In cooperative agreements, the Secretary is authorized to advance...

  19. 77 FR 10743 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-23

    ... . Agreement No.: 011353-036. Title: The Credit Agreement. Parties: Crowley Latin America Services, LLC; Dole..., DC 20006-4007. Synopsis: The amendment deletes Crowley Latin American Services, LLC and a King Ocean entity as a party to the Agreement. Agreement No.: 012155. Title: MSC/Zim South America East Coast...

  20. 7 CFR 947.111 - Marketing agreement.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Marketing agreement. 947.111 Section 947.111 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING... Definitions § 947.111 Marketing agreement. Marketing agreement means Marketing Agreement No. 114, as amended....

  1. 7 CFR 947.111 - Marketing agreement.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Marketing agreement. 947.111 Section 947.111 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING... Definitions § 947.111 Marketing agreement. Marketing agreement means Marketing Agreement No. 114, as amended....

  2. 7 CFR 947.111 - Marketing agreement.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Marketing agreement. 947.111 Section 947.111 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing... Definitions § 947.111 Marketing agreement. Marketing agreement means Marketing Agreement No. 114, as amended....

  3. 27 CFR 70.485 - Closing agreements.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2012-04-01 2011-04-01 true Closing agreements. 70.485... Relating to Alcohol, Tobacco, Firearms, and Explosives Administrative Remedies § 70.485 Closing agreements... taxable period ending prior or subsequent to the date of such agreement. A closing agreement may...

  4. 27 CFR 70.485 - Closing agreements.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2013-04-01 2013-04-01 false Closing agreements. 70.485... Relating to Alcohol, Tobacco, Firearms, and Explosives Administrative Remedies § 70.485 Closing agreements... taxable period ending prior or subsequent to the date of such agreement. A closing agreement may...

  5. 27 CFR 70.485 - Closing agreements.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Closing agreements. 70.485... Relating to Alcohol, Tobacco, Firearms, and Explosives Administrative Remedies § 70.485 Closing agreements... taxable period ending prior or subsequent to the date of such agreement. A closing agreement may...

  6. 27 CFR 70.485 - Closing agreements.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2011-04-01 2011-04-01 false Closing agreements. 70.485... Relating to Alcohol, Tobacco, Firearms, and Explosives Administrative Remedies § 70.485 Closing agreements... taxable period ending prior or subsequent to the date of such agreement. A closing agreement may...

  7. 27 CFR 70.485 - Closing agreements.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2014-04-01 2014-04-01 false Closing agreements. 70.485... Relating to Alcohol, Tobacco, Firearms, and Explosives Administrative Remedies § 70.485 Closing agreements... taxable period ending prior or subsequent to the date of such agreement. A closing agreement may...

  8. 40 CFR 46.170 - Fellowship agreement.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Fellowship agreement. 46.170 Section 46... FELLOWSHIPS Award § 46.170 Fellowship agreement. (a) The “Fellowship Agreement” (EPA Form 5770-8) is the written agreement, including amendments, between EPA and you. The fellowship agreement will state...

  9. 40 CFR 46.170 - Fellowship agreement.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Fellowship agreement. 46.170 Section 46... FELLOWSHIPS Award § 46.170 Fellowship agreement. (a) The “Fellowship Agreement” (EPA Form 5770-8) is the written agreement, including amendments, between EPA and you. The fellowship agreement will state...

  10. 40 CFR 46.170 - Fellowship agreement.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Fellowship agreement. 46.170 Section 46... FELLOWSHIPS Award § 46.170 Fellowship agreement. (a) The “Fellowship Agreement” (EPA Form 5770-8) is the written agreement, including amendments, between EPA and you. The fellowship agreement will state...

  11. 40 CFR 46.170 - Fellowship agreement.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Fellowship agreement. 46.170 Section 46... FELLOWSHIPS Award § 46.170 Fellowship agreement. (a) The “Fellowship Agreement” (EPA Form 5770-8) is the written agreement, including amendments, between EPA and you. The fellowship agreement will state...

  12. 40 CFR 46.170 - Fellowship agreement.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Fellowship agreement. 46.170 Section 46... FELLOWSHIPS Award § 46.170 Fellowship agreement. (a) The “Fellowship Agreement” (EPA Form 5770-8) is the written agreement, including amendments, between EPA and you. The fellowship agreement will state...

  13. Activity and function of the nuclear factor kappaB pathway in human parathyroid tumors.

    PubMed

    Corbetta, S; Vicentini, L; Ferrero, S; Lania, A; Mantovani, G; Cordella, D; Beck-Peccoz, P; Spada, A

    2005-12-01

    Previous studies indicate that nuclear factor kappaB (NF-kappaB) transcription factor is deregulated and overexpressed in several human neoplasias. The aim of this study was to test the hypothesis that the NF-kappaB pathway may be involved in parathyroid tumorigenesis. For this purpose, we determined the level of NF-kappaB activity, evaluated as phosphorylation of the transcription subunit p65, its modulation by specific and non-specific agents and its impact on cyclin D1 expression. Phosphorylated p65 levels present in parathyroid neoplasias (n = 13) were significantly lower than those found in normal tissues (n = 3; mean optical density (OD) 0.19 +/- 0.1 vs 0.4 +/- 0.1, P = 0.007), but there was no significant difference between adenomas and secondary and multiple endocrine neoplasia type 1 (MEN1)-related hyperplasia. Conversely, MEN2A (Cys634Arg)-related parathyroid samples showed extremely high levels of phosphorylated p65 that exhibited a nuclear localization at immunohistochemistry (n = 3). Phosphorylated p65 levels negatively correlated with menin expression (r(2) = 0.42, P = 0.05). Tumor necrosis factor-alpha (TNFalpha) caused a significant increase in phosphorylated p65 levels (183 +/- 13.8% of basal) while calcium sensing receptor (CaR) agonists exerted a significant inhibition (19.2 +/- 3.3% of basal). Although TNFalpha was poorly effective in increasing cyclin D1 expression, NF-kappaB blockade by the specific inhibitor BAY11-7082 reduced FCS-stimulated cyclin D1 by about 60%. Finally, the inhibitory effects of CaR and BAY11-7082 on cyclin D1 expression were not additive - by blocking NF-kappaB CaR activation did not induce a further reduction in cyclin D1 levels. In conclusion, the study demonstrated that in parathyroid tumors: (1) p65 phosphorylation was dramatically increased by RET constitutive activation and was negatively correlated with menin expression, (2) p65 phosphorylation was increased and reduced by TNFalpha and CaR agonists respectively

  14. Energetic Particle Spectral Shapes in Planetary Magnetospheres; Assessment of the Kappa Function

    NASA Astrophysics Data System (ADS)

    Mauk, B.

    2015-12-01

    In assessing the efficacy of the kappa distribution function in space environments, it is useful to follow two paths. First, to what extent do we consider the kappa function (or any function) to represent some kind of universal spectral shape that indicates common physical processes occurring in a wide diversity of space environments? Second, how useful is the kappa function in quantitatively characterizing observed spectral shapes, particularly for the purpose permitting further quantitative analyses of the environment (e. g. wave growth). In this report I evaluate the efficacy of the kappa distribution in representing energetic particle spectral shapes in planetary magnetospheres from both perspectives. In particular, I expand on the extensive treatment provided by Carbary et al. (2014) by taking a more explicit comparative approach between the different planets (Earth, Jupiter, Saturn, Uranus, and Neptune) and also focusing on the most intense (and therefore from my perspective the most interesting) spectra within each of these different planets. There is no question that the "power law tail" represents as close to a universal characteristic of planetary space environments as one could hope to find. Such a universal shape must represent some universality in the energization and/or equilibrating processes. Also, there is no question that such tails must (to be non-divergent) and do roll over to flatter shapes at lower energies. In a number of applications, this basic characteristic has been usefully characterized by the kappa function to extract such parameters of the system as flow velocities. However, at least for the more intense spectra at Earth, Jupiter, Saturn, and Uranus, the kappa function in fact does a relatively poor job in representing the low energy roll-over of energetic particle spectra. Other functional forms have been found to be much more useful for characterizing these spectral shapes over a broad range of energies. And specifically, a very

  15. Statistical crystallography of surface micelle spacing

    NASA Technical Reports Server (NTRS)

    Noever, David A.

    1992-01-01

    The aggregation of the recently reported surface micelles of block polyelectrolytes is analyzed using techniques of statistical crystallography. A polygonal lattice (Voronoi mosaic) connects center-to-center points, yielding statistical agreement with crystallographic predictions; Aboav-Weaire's law and Lewis's law are verified. This protocol supplements the standard analysis of surface micelles leading to aggregation number determination and, when compared to numerical simulations, allows further insight into the random partitioning of surface films. In particular, agreement with Lewis's law has been linked to the geometric packing requirements of filling two-dimensional space which compete with (or balance) physical forces such as interfacial tension, electrostatic repulsion, and van der Waals attraction.

  16. Benzo[a]pyrene inhibits osteoclastogenesis by affecting RANKL-induced activation of NF-kappaB.

    PubMed

    Voronov, I; Li, K; Tenenbaum, H C; Manolson, M F

    2008-05-15

    Exposure to polycyclic aryl hydrocarbons is linked to cancer, immunosuppression and other numerous health problems. We previously demonstrated that exposure to benzo[a]pyrene (BaP), an environmental pollutant present in high concentrations in urban smog and cigarette smoke, inhibits osteoclast differentiation and bone resorption. We hypothesized that this inhibition could be due to crosstalk between the receptor activator of NF-kappaB ligand (RANKL) and AhR signaling cascades competing for NF-kappaB, a common transcription factor for both pathways. RAW264.7 cells (a mouse macrophage cell line capable of differentiating into osteoclasts in the presence of RANKL) were exposed to different concentrations of RANKL and BaP and the effect on NF-kappaB activation, nuclear translocation, as well as the effect of NF-kappaB inhibitors on BaP-mediated CYP1B1 gene expression was measured. The results demonstrated that BaP inhibited both RANKL-induced NF-kappaB activation and nuclear translocation. At the same time, BaP-induced CYP1B1 gene expression was inhibited by two NF-kappaB inhibitors in a dose-dependent manner, demonstrating that NF-kappaB is involved in a BaP-mediated signaling pathway. A reporter gene assay showed that both BaP and RANKL-induced luciferase reporter gene transcription under the control of NF-kappaB response elements. Co-immunoprecipitation results demonstrated that AhR interacted with NF-kappaB p65 in RAW cells and BaP appeared to enhance this interaction. However, in the presence of RANKL, we did not observe any interaction between AhR and p65. These results support our hypothesis that BaP-mediated inhibition of osteoclastogenesis is a consequence of crosstalk between AhR and RANKL signaling pathways competing for the common transcription factor NF-kappaB. PMID:18396263

  17. Transglutaminase 2 gene ablation protects against renal ischemic injury by blocking constant NF-{kappa}B activation

    SciTech Connect

    Kim, Dae-Seok; Kim, Bora; Tahk, Hongmin; Kim, Dong-Hyun; Ahn, Eu-Ree; Choi, Changsun; Jeon, Yoon; Park, Seo Young; Lee, Ho; Oh, Seung Hyun; Kim, Soo-Youl

    2010-12-17

    Research highlights: {yields} No acute renal tubular necrotic lesions were found in TGase2{sup -/-} mice with ischemic kidney injury. {yields} NF-{kappa}B activation is reduced in TGase2{sup -/-} mice with ischemic kidney injury. {yields} Hypoxic stress did not increase NF-{kappa}B activity in MEFs from TGase2{sup -/-} mice. {yields} COX-2 induction is suppressed in TGase2{sup -/-} mice with ischemic kidney injury. -- Abstract: Transglutaminase 2 knockout (TGase2{sup -/-}) mice show significantly reduced inflammation with decreased myofibroblasts in a unilateral ureteral obstruction (UUO) model, but the mechanism remains to be clarified. Nuclear factor-{kappa}B (NF-{kappa}B) activation plays a major role in the progression of inflammation in an obstructive nephropathy model. However, the key factors extending the duration of NF-{kappa}B activation in UUO are not known. In several inflammatory diseases, we and others recently found that TGase 2 plays a key role in extending NF-{kappa}B activation, which contributes to the pathogenesis of disease. In the current study, we found that NF-{kappa}B activity in mouse embryogenic fibroblasts (MEFs) from TGase2{sup -/-} mice remained at the control level while the NF-{kappa}B activity of wild-type (WT) MEFs was highly increased under hypoxic stress. Using the obstructive nephropathy model, we found that NF-{kappa}B activity remained at the control level in TGase2{sup -/-} mouse kidney tissues, as measured by COX-2 expression, but was highly increased in WT tissues. We conclude that TGase 2 gene ablation reduces the duration of NF-{kappa}B activation in ischemic injury.

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

    PubMed Central

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

    2016-01-01

    Background: 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. Methods: 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. Results: 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. Conclusions: These data suggest that the chronic intermittent ethanol-induced increase

  19. Effects of mechanistically distinct NF-kappaB inhibitors on glial inducible nitric-oxide synthase expression.

    PubMed

    Davis, Randall L; Sanchez, Alma C; Lindley, Daniel J; Williams, Simon C; Syapin, Peter J

    2005-06-01

    Nuclear factor (NF)-kappaB is an important regulator of inflammatory gene expression. Transcriptional regulation of Nos2, the inducible nitric-oxide synthase (iNOS) gene, is complex and not fully understood, but appears to be regulated in part by NF-kappaB. To further understand the role of NF-kappaB in Nos2 expression, we compared three functionally distinct NF-kappaB inhibitors on NF-kappaB transactivation and iNOS induction by rat C6 glial cells. Cytokine-induced activation of a consensus NF-kappaB-reporter gene was concentration-dependently inhibited by BAY 11-7082, MG-132, and helenalin. The rank order of potency was MG-132>helenalin>BAY 11-7082, with low concentrations of helenalin stimulating reporter gene activity. Cytokine-stimulated iNOS expression, measured by nitrite accumulation and in vitro l-citrulline production, was similarly reduced by exposing C6 cells to the NF-kappaB inhibitors. Surprisingly, activation of Nos2-reporter gene constructs containing the proximal 188 bp (containing one kappaB site) or proximal 94 bp (no kappaB site) of the rat promoter also was inhibited with the same rank order of potency. Interestingly, low concentrations of helenalin increased activity of both promoter constructs, while BAY 11-7082 poorly inhibited the 94-bp activity. This is the first report describing BAY 11-7082 and helenalin effects on iNOS expression in astroglia. Given the reported mechanism of actions for these inhibitors, cytokine-induced glial iNOS expression appears more sensitive to disruption of proteasome degradation and p65 function than modulation of IkappaB phosphorylation. These findings may foster the design of therapeutic agents aimed at NF-kappaB-associated pathways involved in neuroinflammation, especially iNOS expression.

  20. Predict! Teaching Statistics Using Informational Statistical Inference

    ERIC Educational Resources Information Center

    Makar, Katie

    2013-01-01

    Statistics is one of the most widely used topics for everyday life in the school mathematics curriculum. Unfortunately, the statistics taught in schools focuses on calculations and procedures before students have a chance to see it as a useful and powerful tool. Researchers have found that a dominant view of statistics is as an assortment of tools…

  1. The Importance of the Ubiquitous 'Kappa' Distributions in Space Plasmas (Invited)

    NASA Astrophysics Data System (ADS)

    Scudder, J. D.; Karimabadi, H.

    2013-12-01

    The kappa model for f(v) was originally derived by Olbert (1966) to provide frugal but informative fits to observed particle fluxes from which moments of the underlying plasma could be extracted. Olbert's new fit parameter (kappa) allowed for the ambient plasma to possess reduced kurtosis, which a Gaussian does not. The universality of kappa can easily be overstated, since it cannot fit distributions with a heat flux which is generally important in astrophysical plasmas. Geophysically the frequent use of such a parametrization for the zeroth order energy distribution in the comoving frame acknowledges that the observed plasmas of nature are generally non-thermal, hence kurtotic, which for this author is their principal significance. A key question remains whether the analytically convenient kappa function's kurtotic form is required by the laws of physics, or rather a deft representative of all possible distributions with non-negligible kurtosis and other higher moments. This paper develops why the non-thermal kurtotic f(v) should generally be expected in astrophysical plasmas structured by gravity, driven by their tendency to achieve quasi-neutrality. It will demonstrate the essential role of runaway phenomena in the origin of this kurtosis while showing consistency with observables. This approach provides a rationale why such kurtotic distributions should occur without arguing what its precise shape should be, beyond possessing non-zero skewness and kurtosis. Initial results will be shown that the kappa model for such kurtotic distributions, while better than an Gaussian, may be too rigid to describe the non-thermal distributions of nature at all radial distances from the sun.

  2. Mitochondrial function and nuclear factor-kappaB-mediated signaling in radiation-induced bystander effects.

    PubMed

    Zhou, Hongning; Ivanov, Vladimir N; Lien, Yu-Chin; Davidson, Mercy; Hei, Tom K

    2008-04-01

    Although radiation-induced bystander effects have been well described over the past decade, the mechanisms of the signaling processes involved in the bystander phenomenon remain unclear. In the present study, using the Columbia University charged particle microbeam, we found that mitochondrial DNA-depleted human skin fibroblasts (rho(o)) showed a higher bystander mutagenic response in confluent monolayers when a fraction of the same population were irradiated with lethal doses compared with their parental mitochondrial-functional cells (rho(+)). However, using mixed cultures of rho(o) and rho(+) cells and targeting only one population of cells with a lethal dose of alpha-particles, a decreased bystander mutagenesis was uniformly found in nonirradiated bystander cells of both cell types, indicating that signals from one cell type can modulate expression of bystander response in another cell type. In addition, we found that Bay 11-7082, a pharmacologic inhibitor of nuclear factor-kappaB (NF-kappaB) activation, and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, a scavenger of nitric oxide (NO), significantly decreased the mutation frequency in both bystander rho(o) and rho(+) cells. Furthermore, we found that NF-kappaB activity and its dependent proteins, cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS), were lower in bystander rho(o) cells when compared with their rho(+) counterparts. Our results indicated that mitochondria play an important role in the regulation of radiation-induced bystander effects and that mitochondria-dependent NF-kappaB/iNOS/NO and NF-kappaB/COX-2/prostaglandin E2 signaling pathways are important to the process.

  3. A SIMPLE METHOD FOR MODELING COLLISION PROCESSES IN PLASMAS WITH A KAPPA ENERGY DISTRIBUTION

    SciTech Connect

    Hahn, M.; Savin, D. W.

    2015-08-20

    We demonstrate that a nonthermal distribution of particles described by a kappa distribution can be accurately approximated by a weighted sum of Maxwell–Boltzmann distributions. We apply this method to modeling collision processes in kappa-distribution plasmas, with a particular focus on atomic processes important for solar physics. The relevant collision process rate coefficients are generated by summing appropriately weighted Maxwellian rate coefficients. This method reproduces the rate coefficients for a kappa distribution to an estimated accuracy of better than 3%. This is equal to or better than the accuracy of rate coefficients generated using “reverse-engineering” methods, which attempt to extract the needed cross sections from the published Maxwellian rate coefficient data and then reconvolve the extracted cross sections with the desired kappa distribution. Our approach of summing Maxwellian rate coefficients is easy to implement using existing spectral analysis software. Moreover, the weights in the sum of the Maxwell–Boltzmann distribution rate coefficients can be found for any value of the parameter κ, thereby enabling one to model plasmas with a time-varying κ. Tabulated Maxwellian fitting parameters are given for specific values of κ from 1.7 to 100. We also provide polynomial fits to these parameters over this entire range. Several applications of our technique are presented, including the plasma equilibrium charge state distribution (CSD), predicting line ratios, modeling the influence of electron impact multiple ionization on the equilibrium CSD of kappa-distribution plasmas, and calculating the time-varying CSD of plasmas during a solar flare.

  4. Identification of kappa opioid receptors in the immune system by indirect immunofluorescence.

    PubMed Central

    Lawrence, D M; el-Hamouly, W; Archer, S; Leary, J F; Bidlack, J M

    1995-01-01

    A method to visualize the kappa opioid receptor is described that uses a high-affinity fluorescein-conjugated opioid ligand and indirect immunofluorescence with the phycoerythrin fluorophore to amplify the signal. The mouse thymoma cell line R1E/TL8x.1.G1.OUAr.1 (R1EGO), which expresses the kappa 1 but not mu or delta opioid receptors, was used as a positive control for fluorescence labeling. A fluorescein isothiocyanate-conjugated arylacetamide (FITC-AA) compound displaying high affinity for the kappa opioid receptor was synthesized. R1EGO cells were incubated with FITC-AA, in the absence or presence of the kappa-selective opioid antagonist nor-binaltorphimine (nor-BNI) as a competitor. By using fluorescence microscopy and flow cytometry, incubation of R1EGO cells with FITC-AA alone was not sufficient for the detection of specific staining of the kappa opioid receptor. To amplify the FITC-AA fluorescence, the fluorescein served as a hapten for subsequent antibody detection. R1EGO cells were incubated with FITC-AA, followed by biotinylated rabbit anti-fluorescein IgG and extravidin-conjugated R-phycoerythrin. By using this approach, R1EGO cells were stained with phycoerythrin-amplified FITC-AA, and the staining was displaced with nor-BNI. Flow cytometry showed that titrations of both FITC-AA and nor-BNI produced saturable concentration-dependent changes in the median phycoerythrin fluorescence intensity, with optimal staining at 30 microM FITC-AA. Up to 80% of the fluorescence above background was inhibited by nor-BNI. Freshly isolated thymocytes from C57BL/6ByJ mice also showed nor-BNI-sensitive staining with the FITC-AA amplification. This sensitive method of indirect phycoerythrin immunofluorescence can be used to amplify any fluorescein-conjugated opioid ligand for the detection of opioid receptors. Images Fig. 2 PMID:7862634

  5. Ketamine suppresses intestinal NF-kappa B activation and proinflammatory cytokine in endotoxic rats

    PubMed Central

    Sun, Jie; Wang, Xiao-Dong; Liu, Hong; Xu, Jian-Guo

    2004-01-01

    AIM: To investigate the protective effect of ketamine on the endotoxin-induced proinflammatory cytokines and NF-kappa B activation in the intestine. METHODS: Adult male Wistar rats were randomly divided into 6 groups: (a) normal saline control, (b) challenged with endotoxin (5 mg/kg) and treated by saline, (c) challenged with endotoxin (5 mg/kg) and treated by ketamine (0.5 mg/kg), (d) challenged with endotoxin (5 mg/kg) and treated by ketamine (5 mg/kg ), (e) challenged with endotoxin (5 mg/kg) and treated by ketamine (50 mg/kg), and (f) saline injected and treated by ketamine (50 mg/kg). After 1, 4 or 6 h, TNF-α and IL-6 mRNA were investigated in the tissues of the intestine (jejunum) by RT-PCR. TNF-α and IL-6 were measured by ELISA. We used electrophoretic mobility shift assay (EMSA) to investigate NF-kappa B activity in the intestine. RESULTS: NF-kappa B activity, the expression of TNF-α and IL-6 were enhanced in the intestine by endotoxin. Ketamine at a dose of 0.5 mg/kg could suppress endotoxin-induced TNF-α mRNA and protein elevation and inhibit NF-kappa B activation in the intestine. However the least dosage of ketamine to inhibit IL-6 was 5 mg/kg in our experiment. CONCLUSION: Ketamine can suppress endotoxin-induced production of proinflammatory cytokines such as TNF-α and IL-6 production in the intestine. This suppressive effect may act through inhibiting NF-kappa B. PMID:15052687

  6. IASGA: A SAS MACRO Program for Interrater Agreement Studies of Qualitative Data via a Generalizability Approach.

    ERIC Educational Resources Information Center

    Li, Mao-Neng Fred; Lautenschlager, Gary J.

    1999-01-01

    Describes a Statistical Analysis System (SAS) MACRO for computing various indices of interrater agreement, including a new generalizability coefficient, for categorical data in a single-facet, crossed design. (Author/SLD)

  7. Statistical mechanics of nucleosomes

    NASA Astrophysics Data System (ADS)

    Chereji, Razvan V.

    Eukaryotic cells contain long DNA molecules (about two meters for a human cell) which are tightly packed inside the micrometric nuclei. Nucleosomes are the basic packaging unit of the DNA which allows this millionfold compactification. A longstanding puzzle is to understand the principles which allow cells to both organize their genomes into chromatin fibers in the crowded space of their nuclei, and also to keep the DNA accessible to many factors and enzymes. With the nucleosomes covering about three quarters of the DNA, their positions are essential because these influence which genes can be regulated by the transcription factors and which cannot. We study physical models which predict the genome-wide organization of the nucleosomes and also the relevant energies which dictate this organization. In the last five years, the study of chromatin knew many important advances. In particular, in the field of nucleosome positioning, new techniques of identifying nucleosomes and the competing DNA-binding factors appeared, as chemical mapping with hydroxyl radicals, ChIP-exo, among others, the resolution of the nucleosome maps increased by using paired-end sequencing, and the price of sequencing an entire genome decreased. We present a rigorous statistical mechanics model which is able to explain the recent experimental results by taking into account nucleosome unwrapping, competition between different DNA-binding proteins, and both the interaction between histones and DNA, and between neighboring histones. We show a series of predictions of our new model, all in agreement with the experimental observations.

  8. Reverse-Transcriptase PCR Detection of Leptospira: Absence of Agreement with Single-Specimen Microscopic Agglutination Testing

    PubMed Central

    Waggoner, Jesse J.; Balassiano, Ilana; Mohamed-Hadley, Alisha; Vital-Brazil, Juliana Magalhães; Sahoo, Malaya K.; Pinsky, Benjamin A.

    2015-01-01

    Background Reference diagnostic tests for leptospirosis include nucleic acid amplification tests, bacterial culture, and microscopic agglutination testing (MAT) of acute and convalescent serum. However, clinical laboratories often do not receive paired specimens. In the current study, we tested serum samples using a highly sensitive real-time nucleic acid amplification test for Leptospira and compared results to MAT performed on the same specimens. Methods/Principal Findings 478 serum samples from suspected leptospirosis cases in Rio de Janeiro were tested using a real-time RT-PCR for the diagnosis of leptospirosis, malaria and dengue (the Lepto-MD assay). The Lepto-MD assay detects all species of Leptospira (saprophytic, intermediate, and pathogenic), and in the current study, we demonstrate that this assay amplifies both Leptospira RNA and DNA. Dengue virus RNA was identified in 10 patients, and no cases of malaria were detected. A total of 65 samples (13.6%) were positive for Leptospira: 35 samples (7.3%) in the Lepto-MD assay, 33 samples (6.9%) by MAT, and 3 samples tested positive by both (kappa statistic 0.02). Poor agreement between methods was consistent regardless of the titer used to define positive MAT results or the day of disease at sample collection. Leptospira nucleic acids were detected in the Lepto-MD assay as late as day 22, and cycle threshold values did not differ based on the day of disease. When Lepto-MD assay results were added to the MAT results for all patients in 2008 (n=818), the number of detected leptospirosis cases increased by 30.4%, from 102 (12.5%) to 133 (16.3%). Conclusions/Significance This study demonstrates a lack of agreement between nucleic acid detection of Leptospira and single-specimen MAT, which may result from the clearance of bacteremia coinciding with the appearance of agglutinating antibodies. A combined testing strategy for acute leptospirosis, including molecular and serologic testing, appears necessary to maximize

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

    SciTech Connect

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

    2012-02-17

    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 important 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

  10. International Agreement on Planetary Protection

    NASA Technical Reports Server (NTRS)

    2000-01-01

    The maintenance of a NASA policy, is consistent with international agreements. The planetary protection policy management in OSS, with Field Center support. The advice from internal and external advisory groups (NRC, NAC/Planetary Protection Task Force). The technology research and standards development in bioload characterization. The technology research and development in bioload reduction/sterilization. This presentation focuses on: forward contamination - research on the potential for Earth life to exist on other bodies, improved strategies for planetary navigation and collision avoidance, and improved procedures for sterile spacecraft assembly, cleaning and/or sterilization; and backward contamination - development of sample transfer and container sealing technologies for Earth return, improvement in sample return landing target assessment and navigation strategy, planning for sample hazard determination requirements and procedures, safety certification, (liaison to NEO Program Office for compositional data on small bodies), facility planning for sample recovery system, quarantine, and long-term curation of 4 returned samples.

  11. Inhibition of NF-{kappa}B1 and NF-{kappa}B2 activation in prostate cancer cells treated with antibody against the carboxyl terminal domain of GRP78: Effect of p53 upregulation

    SciTech Connect

    Misra, U.K.; Kaczowka, S.; Pizzo, S.V.

    2010-02-19

    Ligation of cancer cell surface GRP78 by activated {alpha}{sub 2}-macroglobulin ({alpha}{sub 2}M{sup *}) triggers pro-proliferative and anti-apoptotic signaling pathways. Cancer patients who develop autoantibodies to the {alpha}{sub 2}M{sup *} binding site in GRP78 have a poor prognosis since these antibodies are receptor agonists. The NF-{kappa}B family of transcription factors induces expression of genes affecting cell growth and differentiation. NF-{kappa}B1 plays a major regulatory role in controlling innate immunity and inflammation, whereas NF-{kappa}B2 plays a greater role in cancer cell proliferation. Here we report that treatment of prostate cancer cells with antibody directed against the carboxyl terminal domain of GRP78 inhibits {alpha}{sub 2}M{sup *}-induced activation of NF-{kappa}B2 by {approx}50% while exerting a lesser effect of {approx}20% on NF-{kappa}B1 activation. Treatment of these cells nearly abolished {alpha}{sub 2}M{sup *}-induced activation of IKK{alpha} involved in the activation of NF-{kappa}B2. This antibody also suppressed {alpha}{sub 2}M{sup *}-induced phosphorylation of IKK{alpha}, IKK{alpha}/{beta}, I{kappa}B{alpha}, and I{kappa}B{beta} as well as levels of NIK. Antibody treatment of cancer cells elevated pro-apoptotic p21WAF and p27kip while reducing cyclin D1 levels. These studies demonstrate that antibody directed against the carboxyl terminal domain of GRP78 inhibits the pro-proliferative NF-{kappa}B signaling cascade in cancer cells.

  12. Glucose ingestion induces an increase in intranuclear nuclear factor kappaB, a fall in cellular inhibitor kappaB, and an increase in tumor necrosis factor alpha messenger RNA by mononuclear cells in healthy human subjects.

    PubMed

    Aljada, Ahmad; Friedman, Jay; Ghanim, Husam; Mohanty, Priya; Hofmeyer, Deborah; Chaudhuri, Ajay; Dandona, Paresh

    2006-09-01

    Because hyperglycemia is a major detrimental factor in the prognosis of acute cardiovascular conditions such as acute myocardial infarction (AMI) and stroke, and because an acute glucose challenge in healthy subjects has been shown to induce oxidative stress in mononuclear cells (MNCs), we have now investigated whether glucose induces inflammatory stress at the cellular and molecular level. Glucose ingestion (75 g in 300 mL water) in healthy human subjects resulted in an increase in intranuclear nuclear factor kappaB (NF-kappaB) binding, the reduction of inhibitor kappaB alpha (IkappaBalpha) protein, and an increase in the activity of inhibitor kappaB kinase (IKK) and the expression of IKKalpha and IKKbeta, the enzymes that phosphorylate IkappaBalpha, in MNCs. Glucose intake caused an increase in NF-kappaB binding to NF-kappaB2, NF-kappaB2a, and NF-kappaB3 sequences in the promoter site of tumor necrosis factor alpha (TNF-alpha) gene along with an increase in the expression of TNF-alpha messenger RNA in MNCs. Membranous p47(phox) subunit, an index of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expression and activation, also increased after glucose intake. We conclude that glucose intake induces an immediate increase in intranuclear NF-kappaB binding, a fall in IkappaBalpha, an increase in IKKalpha, IKKbeta, IKK activity, and messenger RNA expression of TNF-alpha in MNCs in healthy subjects. These data are consistent with profound acute pro-inflammatory changes in MNCs after glucose intake.

  13. Effect of prolactin, beta-lactoglobulin, and kappa-casein genotype on milk yield in East Friesian sheep.

    PubMed

    Staiger, E A; Thonney, M L; Buchanan, J W; Rogers, E R; Oltenacu, P A; Mateescu, R G

    2010-04-01

    The effect of prolactin (PRL), beta-lactoglobulin (beta-LG), and kappa-casein (CSN3) on milk yield was estimated in an East Friesian dairy sheep population from Old Chatham Sheepherding Company, New York. Genotypes were determined by PCR amplification followed by digestion with HaeIII and RsaI for PRL and beta-LG, respectively, and by PCR amplification for CSN3. Monthly milking records and pedigree information were used to evaluate the effect of each polymorphism on milk yield. Results indicated that PRL genotype had a significant effect on milk yield. Ewes carrying one A allele produced 110.6g more milk per day than ewes with no A alleles. There was no statistical difference between ewes with only one A allele and ewes with 2 A alleles. No association among polymorphisms at the beta-LG and CSN3 loci and milk yield was found. The results presented in this study indicate that the PRL gene is a potential marker that could be used in selection programs for improving milk yield in dairy sheep.

  14. Salivary soluble receptor activator of nuclear factor kappa B ligand/osteoprotegerin ratio in periodontal disease and health

    PubMed Central

    Tabari, Zahra Alizadeh; Azadmehr, Abbas; Tabrizi, Mohammad Amir Alizadeh; Hamissi, Jalaloddin

    2013-01-01

    Purpose The receptor activator of nuclear factor kappa B (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system plays a significant role in osteoclastogenesis, activation of osteoclasts, and regulation of bone resorption. This study aimed to evaluate the use of the salivary soluble RANKL (sRANKL)/OPG ratio as a diagnostic marker for periodontitis in nonsmokers. Methods Twenty-five patients with chronic periodontitis and 25 individuals with a healthy periodontium were enrolled in this study. Samples containing 5 mL of unstimulated saliva were obtained from each subject. Salivary sRANKL and OPG concentrations were determined using a standard enzyme-linked immunosorbent assay. Statistical analysis was performed using SPSS ver. 18.0. Results The levels of sRANKL and OPG were detectable in all of the samples. Positive relationships were found between the plaque index and clinical attachment level and both the salivary concentration of sRANKL and the salivary sRANKL/OPG ratio (P<0.05). The salivary concentration of sRANKL and the sRANKL/OPG ratio were significantly higher in the periodontitis group than in the healthy group (P=0.004 and P=0.001, respectively). In contrast, the OPG concentration showed no significant differences between the groups (P=0.455). Conclusions These findings suggest that the salivary sRANKL/OPG ratio may be helpful in the screening and diagnosis of periodontitis. However, longitudinal studies with larger populations are needed to confirm these results. PMID:24236245

  15. Parent Agreement on Ratings of Children's Attention Deficit/Hyperactivity Disorder and Broadband Externalizing Behaviors

    ERIC Educational Resources Information Center

    Langberg, Joshua M.; Epstein, Jeffery N.; Simon, John O.; Loren, Richard E. A.; Arnold, L. Eugene; Hechtman, Lily; Hinshaw, Stephen P.; Hoza, Betsy; Jensen, Peter S.; Pelham, William E.; Swanson, James M.; Wigal, Timothy

    2010-01-01

    Mothers and fathers often disagree in their ratings of child behavior, as evidenced clinically and as supported by a substantial literature examining parental agreement on broadband rating scales. The present study examined mother-father agreement on "Diagnostic and Statistical Manual"-based symptom-specific ratings of…

  16. Rapid induction in regenerating liver of RL/IF-1 (an I kappa B that inhibits NF-kappa B, RelB-p50, and c-Rel-p50) and PHF, a novel kappa B site-binding complex.

    PubMed

    Tewari, M; Dobrzanski, P; Mohn, K L; Cressman, D E; Hsu, J C; Bravo, R; Taub, R

    1992-06-01

    The liver is one of the few adult tissues that has the capacity to regenerate following hepatectomy or toxic damage. In examining the early growth response during hepatic regeneration, we found that a highly induced immediate-early gene in regenerating liver encodes RL/IF-1 (regenerating liver inhibitory factor) and is the rat homolog of human MAD-3 and probably of chicken pp40. RL/IF-1 has I kappa B activity of broad specificity in that it inhibits the binding of p50-p65 NF-kappa B, c-Rel-p50, and RelB-p50, but not p50 homodimeric NF-kappa B, to kappa B sites. Like RL/IF-1, several members of the NF-kappa B and rel family of transcription factors are immediate-early genes in regenerating liver and mitogen-treated cells. We examined changes in kappa B site binding activity during liver regeneration and discovered a rapidly induced novel kappa B site-binding complex designated PHF [posthepatectomy factor(s)]. PHF is induced over 1,000-fold within minutes posthepatectomy in a protein synthesis-independent manner, with peak activity at 30 min, and is not induced by sham operation. PHF is distinct from p50-p65 NF-kappa B, which is present only in the inactive form in liver posthepatectomy. Although early PHF complexes do not interact strongly with anti-p50 antibodies, PHF complexes present later (3 to 5 h) posthepatectomy react strongly, suggesting that they contain a p50 NF-kappa B subunit. Unlike p50-p65 NF-kappa B, c-Rel-p50, and RelB-p50 complexes, PHF binding to kappa B sites is not inhibited by RL/IF-1. One role of RL/IF-1 in liver regeneration may be to inhibit p50-p65 NF-kappa B activity present in hepatic cells, allowing for the preferential binding of PHF to kappa B sites. Because PHF is induced immediately posthepatectomy in the absence of de novo protein synthesis, PHF could have a role in the regulation of liver-specific immediate-early genes in regenerating liver.

  17. Nonstationary statistical theory for multipactor

    SciTech Connect

    Anza, S.; Vicente, C.; Gil, J.

    2010-06-15

    This work presents a new and general approach to the real dynamics of the multipactor process: the nonstationary statistical multipactor theory. The nonstationary theory removes the stationarity assumption of the classical theory and, as a consequence, it is able to adequately model electron exponential growth as well as absorption processes, above and below the multipactor breakdown level. In addition, it considers both double-surface and single-surface interactions constituting a full framework for nonresonant polyphase multipactor analysis. This work formulates the new theory and validates it with numerical and experimental results with excellent agreement.

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

    SciTech Connect

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

    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. 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.

  19. Death receptor-4 (DR4) expression is regulated by transcription factor NF-kappaB in response to etoposide treatment.

    PubMed

    Mendoza, Francisco José; Ishdorj, Ganchimeg; Hu, Xiaojie; Gibson, Spencer B

    2008-06-01

    Tumour necrosis factor related apoptosis inducing ligand (TRAIL) binds to death receptor 4 (DR4) activating the apoptotic signalling pathway. DNA damaging agents (genotoxins) such as etoposide increase DR4 expression and when combined with TRAIL induce a synergistic apoptotic response. The mechanism for up-regulation of DR4 expression following genotoxin treatment is not well understood. Herein, we determined that transcription factor NF-kappaB plays a role in genotoxin induced DR4 expression. Increased expression of DR4 following etoposide treatment is blocked by inhibition of the NF-kappaB pathway. Moreover, expression of the p65 subunit of NF-kappaB is sufficient to increase DR4 protein levels. Indeed, knockdown of p65 by RNA interference blocked etoposide up-regulation of DR4. We further identified a functional NF-kappaB binding site located in the DR4 promoter. Mutation of this site abrogates the induction of luciferase activity after p65 over-expression. Furthermore, electromobility shift assays and chromatin immunoprecipitaton suggest that NF-kappaB binds to this site upon etoposide treatment. MEK kinase 1 (MEKK1) is a serine threonine kinase that is activated following etoposide treatment and activates NF-kappaB. Expression of the kinase inactive MEKK1 (MEKK1-KM) abrogates the up-regulation of DR4 after etoposide treatment. Taken together, NF-kappaB plays a role in up-regulation of DR4 following etoposide treatment.

  20. NF-kappaB-inhibited acute myeloid leukemia cells are rescued from apoptosis by heme oxygenase-1 induction.

    PubMed

    Rushworth, Stuart A; Bowles, Kristian M; Raninga, Prahlad; MacEwan, David J

    2010-04-01

    Despite high basal NF-kappaB activity in acute myeloid leukemia (AML) cells, inhibiting NF-kappaB in these cells has little or no effect on inducing apoptosis. We previously showed that heme oxygenase-1 (HO-1) underlies this resistance of AML to tumor necrosis factor-induced apoptosis. Here, we describe a mechanism by which HO-1 is a silent antiapoptotic factor only revealed when NF-kappaB is inhibited, thus providing a secondary antiapoptotic mechanism to ensure AML cell survival and chemoresistance. We show that inhibition of NF-kappaB increased HO-1 expression in primary AML cells compared with that of nonmalignant cells. In addition, we observed this suppressed HO-1 level in AML cells compared with CD34(+) nonmalignant control cells. Using chromatin immunoprecipitation assay and small interfering RNA knockdown, we showed that the NF-kappaB subunits p50 and p65 control this suppression of HO-1 in AML cells. Finally, we showed that inhibition of HO-1 and NF-kappaB in combination significantly induced apoptosis in AML cells but not in noncancerous control cells. Thus, NF-kappaB inhibition combined with HO-1 inhibition potentially provides a novel therapeutic approach to treat chemotherapy-resistant forms of AML.

  1. The plasmacytoma J558L lacks constitutively active NF-kappa B and is deficient in early response gene activation.

    PubMed

    Anderson, M T; Wims, L A; Morrison, S L

    1991-12-01

    In mature B cells the nuclear factor NF-kappa B which binds within the kappa enhancer is constitutively present in the nucleus. However, the lambda light chain producing myeloma J558L has been found to lack constitutively functional NF-kappa B. Deoxycholate released functional NF-kappa B from cytoplasmic extracts and functional NF-kappa B was present in J558L following cycloheximide but not phorbol ester treatment. J558L was also unable to respond to phorbol ester stimulation with synthesis of mRNA from the early response gene TIS11. J558L differs from S107, another myeloma which was found to be deficient in the synthesis of NF-kappa B but not in the activation of TIS11. Somatic cell hybrids were used to further define the defect in J558L; hybrids were made with the myelomas S107 and S194 and the pre-B cell line 70Z/3. In general, complementation of the defect in J558L was observed; however there was not a direct correlation between the levels of TIS11 mRNA and NF-kappa B expression in the somatic cell hybrids, suggesting that the pathways of activation of these genes, while possibly sharing common elements, are not identical. The defect in J558L was surprising given that it has frequently been used for the expression of transfected light chain genes.

  2. RelB, a new Rel family transcription activator that can interact with p50-NF-kappa B.

    PubMed Central

    Ryseck, R P; Bull, P; Takamiya, M; Bours, V; Siebenlist, U; Dobrzanski, P; Bravo, R

    1992-01-01

    We have identified a serum-inducible gene, relB, which encodes a protein of 558 amino acids containing a region with high similarity to c-Rel and other members of the Rel family. Transcriptional activation analysis of GAL4-RelB fusion proteins in yeast cells reveals that RelB contains in its C-terminal 180 amino acids a transcriptional activation domain. The N-terminal part including the region of similarity with the Rel family shows no detectable transcriptional activity. RelB does not bind with high affinity to NF-kappa B sites, but heterodimers between RelB and p50-NF-kappa B do bind to different NF-kappa B-binding sites with a similar affinity to that shown by p50-NF-kappa B homodimers. However, RelB/p50-NF-kappa B heterodimers, in contrast to p50-NF-kappa B homodimers, transactivate transcription of a promoter containing a kappa B-binding site. Images PMID:1732739

  3. Hypoxia stimulates via separate pathways ERK phosphorylation and NF-kappaB activation in skeletal muscle cells in primary culture.

    PubMed

    Osorio-Fuentealba, César; Valdés, Juan Antonio; Riquelme, Denise; Hidalgo, Jorge; Hidalgo, Cecilia; Carrasco, María Angélica

    2009-04-01

    Mammalian cells sense oxygen levels and respond to hypoxic conditions through the regulation of multiple signaling pathways and transcription factors. Here, we investigated the effects of hypoxia on the activity of two transcriptional regulators, ERK1/2 and NF-kappaB, in skeletal muscle cells in primary culture. We found that hypoxia significantly enhanced ERK1/2 phosphorylation and that it stimulated NF-kappaB-dependent gene transcription as well as nuclear translocation of a green fluorescent protein-labeled p65 NF-kappaB isoform. Phosphorylation of ERK1/2- and NF-kappaB-dependent transcription by hypoxia required calcium entry through L-type calcium channels. Calcium release from ryanodine-sensitive stores was also necessary for ERK1/2 activation but not for NF-kappaB-dependent-transcription. N-acetylcysteine, a general scavenger of reactive oxygen species, blocked hypoxia-induced ROS generation but did not affect the stimulation of ERK1/2 phosphorylation induced by hypoxia. In contrast, NF-kappaB activation was significantly inhibited by N-acetylcysteine and did not depend on ERK1/2 stimulation, as shown by the lack of effect of the upstream ERK inhibitor U-0126. These separate pathways of activation of ERK1/2 and NF-kappaB by hypoxia may contribute to muscle adaptation in response to hypoxic conditions. PMID:19179647

  4. Agreement of umbilical cord drug and cotinine levels with maternal self-report of drug use and smoking during pregnancy

    PubMed Central

    Wright, Tricia E; Milam, Kristen A; Rougee, Luc; Tanaka, Marissa D; Collier, Abby C

    2011-01-01

    Objective We undertook this study to assess the agreement between fetal umbilical cord drug levels and maternal self-report. Study Design Cord samples were collected from 103 placentas after delivery as a sub-project of the larger Pacific Research Center for Early Human Development (PRCEHD) study. These cord samples were then processed to obtain cord lysates and enzyme-linked immunosorbent assay (ELISA) performed for cotinine and illicit drugs. Levels of each of these substances were compared with clinical information. Results We found fair agreement between self-reported smoking and cotinine levels (kappa = 0.26 (0.07–0.5)) as well as slight agreement with current drug use and positive drug levels (kappa = 0.19 (−0.05–0.4)). Compared with maternal self-report, sensitivity of cotinine levels was 27% and specificity was 98%. Sensitivity of positive cord illicit drug levels was 32% and specificity was 85%. Conclusion Umbilical cords provide another independent measure of maternal drug use and are readily available. To our knowledge, this is the first study to measure cotinine levels in the umbilical cord tissue. PMID:21151006

  5. Inter-rater agreement, sensitivity, and specificity of the prone hip extension test and active straight leg raise test

    PubMed Central

    2014-01-01

    Background Two clinical tests used to assess for neuromuscular control deficits in low back pain (LBP) patients are the prone hip extension (PHE) test and active straight leg raise (ASLR) test. For these tests, it has been suggested examiners classify patients as “positive” or “negative” based on the presence or absence (respectively) of specific “abnormal” lumbopelvic motion patterns. The inter-rater agreement of such a classification scheme has been reported for the PHE test, but not for the ASLR test. In addition, the sensitivity and specificity of such classification schemes have not been reported for either test. The primary objectives of the current study were to investigate: 1) the inter-rater agreement of the examiner-reported classification schemes for these two tests, and 2) the sensitivity and specificity of the classification schemes. Methods Thirty participants with LBP and 40 asymptomatic controls took part in this cross-sectional observational study. Participants performed 3–4 repetitions of each test whilst two examiners classified them as “positive” or “negative” based on the presence or absence (respectively) of specific “abnormal” lumbopelvic motion patterns. The inter-rater agreement (Kappa statistic), sensitivity (LBP patients), and specificity (controls) were calculated for each test. Results Both tests demonstrated substantial inter-rater agreement (PHE test: Kappa = 0.76, 95% CI = 0.57-0.95, p < 0.001; ASLR test: Kappa = 0.76, 95% CI = 0.57-0.96, p < 0.001). For the PHE test, the sensitivity was 0.18-0.27 and the specificity was 0.63-0.78; the odds ratio (OR) of “positive” classifications in the LBP group was 1.25 (95% CI = 0.58-2.72; Examiner 1) and 1.27 (95% CI = 0.52-3.12; Examiner 2). For the ASLR test, the sensitivity was 0.20-0.25 and the specificity was 0.84-0.86; the OR of “positive” classifications in the LBP group was 1.72 (95% CI = 0.75-3.95; Examiner 1) and 1

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

    SciTech Connect

    Zhong, Xia; Li, Xiaonan; Liu, Fuli; Tan, Hui; Shang, Deya

    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 inhibited 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.

  7. Lipopolysaccharide and TNF-alpha activate the nuclear factor kappa B pathway in the human placental JEG-3 cells.

    PubMed

    Lappas, M; Yee, K; Permezel, M; Rice, G E

    2006-01-01

    Up-regulation of pro-inflammatory cytokines, cyclooxygenase (COX-2) and prostaglandins is a critical factor driving human term labour and inflammation-associated preterm labour. Nuclear factor kappa B (NF-kappaB) is activated in response to a number of inflammatory mediators, including cytokines and lipopolysaccharide (LPS). The aim of this study was (i) to investigate if TNF-alpha and LPS activate the NF-kappaB pathway; and (ii) to use short interfering RNA (siRNA) against inhibitor kappaB kinase (IKK)-beta to confirm the role of the NF-kappaB pathway in the regulation of pro-inflammatory mediators in human placental JEG-3 cells. JEG-3 cells (3 independent experiments) were (i) incubated in the presence or absence of 10 microg/ml LPS or 20 ng/ml TNF-alpha, or (ii) transfected with 100 nM IKK-beta siRNA. Incubation of JEG-3 cells with LPS and TNF-alpha increased the expression of cytoplasmic IKK-beta and phosphorylated IkappaB-alpha, and nuclear NF-kappaB proteins p50 and p65. This was associated with a concurrent increase in COX-2 protein, and IL-6 and PGF2alpha release from JEG-3 cells. Treatment of cells with BAY 11-7082 at 50 microM significantly inhibited basal, LPS- and TNF-alpha-induced NF-kappaB and COX-2 expression, and IL-6 and PGF2alpha release. Transfection of JEG-3 cells with IKK-beta siRNA significantly decreased IL-6 and PGF2alpha release. The data presented in this study demonstrate that pro-inflammatory mediators regulate the NF-kappaB transcription pathway in human JEG-3 cells, and the IKK-beta/NF-kappaB pathway is a regulator of inflammatory mediators in placental JEG-3 cells.

  8. Iron-dependent activation of NF-kappaB in Kupffer cells: a priming mechanism for alcoholic liver disease.

    PubMed

    Xiong, Shigang; She, Hongyun; Sung, Chin K; Tsukamoto, Hidekazu

    2003-06-01

    Alcoholic liver disease is associated with hepatic iron accumulation, and iron supplementation exacerbates alcoholic liver disease, suggesting the pathogenic role of iron in alcoholic liver disease. We have tested a hypothesis that iron plays a signaling role in activation of redox-sensitive nuclear factor-kappa B (NF-kappaB) and that increased iron content results in heightened expression of proinflammatory cytokines in Kupffer cells because of this signaling. In cultured Kupffer cells isolated from normal rats, treatment with a lipophilic iron chelator, 1,2-dimethyl-3-hydroxypyrid-4-one (L1), markedly reduced lipopolysaccharide (LPS)-induced NF-kappaB activation and expression of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6. Kupffer cells, isolated from rats with experimentally induced alcoholic liver disease, had significant increases in nonheme iron content, NF-kappaB binding, and mRNA expression for TNF-alpha and macrophage inflammatory protein-1. Ex vivo L1 treatment normalized all these parameters. Addition of ferrous iron to cultured normal rat Kupffer cells increased I-kappa B kinase (IKK) activity at 15 min and NF-kappaB binding at 30 min. L1 pretreatment completely abrogated both effects. Moreover, the iron treatment increased TNF-alpha release and TNF-alpha promoter activity in a NF-kappaB-dependent manner. Ferrous iron also transiently decreased cytoplasmic I-kappa B-alpha (IkappaB-alpha), with concomitant increases in nuclear p65 protein and DNA binding of p65/p50. Taken together, these results support the existence of iron-dependent signaling for activation of IKK/NF-kappaB in Kupffer cells, and this iron signaling serves as a target for a potential priming effect for the pathogenesis of experimental alcoholic liver disease.

  9. Uncoupling of inflammation and insulin resistance by NF-kappaB in transgenic mice through elevated energy expenditure.

    PubMed

    Tang, Tianyi; Zhang, Jin; Yin, Jun; Staszkiewicz, Jaroslaw; Gawronska-Kozak, Barbara; Jung, Dae Young; Ko, Hwi Jin; Ong, Helena; Kim, Jason K; Mynatt, Randy; Martin, Roy J; Keenan, Michael; Gao, Zhanguo; Ye, Jianping

    2010-02-12

    To study the metabolic activity of NF-kappaB, we investigated phenotypes of two different mouse models with elevated NF-kappaB activities. The transcriptional activity of NF-kappaB is enhanced either by overexpression of NF-kappaB p65 (RelA) in aP2-p65 mice or inactivation of NF-kappaB p50 (NF-kappaB1) through gene knock-out. In these models, energy expenditure was elevated in day and night time without a change in locomotion. The mice were resistant to adulthood obesity and diet-induced obesity without reduction in food intake. The adipose tissue growth and adipogenesis were inhibited by the elevated NF-kappaB activity. Peroxisome proliferator-activator receptor gamma expression was reduced by NF-kappaB at the transcriptional level. The two models exhibited elevated inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6) in adipose tissue and serum. However, insulin sensitivity was not reduced by the inflammation in the mice on a chow diet. On a high fat diet, the mice were protected from insulin resistance. The glucose infusion rate was increased more than 30% in the hyperinsulinemic-euglycemic clamp test. Our data suggest that the transcription factor NF-kappaB promotes energy expenditure and inhibits adipose tissue growth. The two effects lead to prevention of adulthood obesity and dietary obesity. The energy expenditure may lead to disassociation of inflammation with insulin resistance. The study indicates that inflammation may prevent insulin resistance by eliminating lipid accumulation.

  10. Interobserver Agreement of Confocal Laser Endomicroscopy for Bladder Cancer

    PubMed Central

    Chang, Timothy C.; Liu, Jen-Jane; Hsiao, Shelly T.; Pan, Ying; Mach, Kathleen E.; Leppert, John T.; McKenney, Jesse K.; Rouse, Robert V.

    2013-01-01

    Abstract Background and Purpose Emerging optical imaging technologies such as confocal laser endomicroscopy (CLE) hold promise in improving bladder cancer diagnosis. The purpose of this study was to determine the interobserver agreement of image interpretation using CLE for bladder cancer. Methods Experienced CLE urologists (n=2), novice CLE urologists (n=6), pathologists (n=4), and nonclinical researchers (n=5) were recruited to participate in a 2-hour computer-based training consisting of a teaching and validation set of intraoperative white light cystoscopy (WLC) and CLE video sequences from patients undergoing transurethral resection of bladder tumor. Interobserver agreement was determined using the κ statistic. Results Of the 31 bladder regions analyzed, 19 were cancer and 12 were benign. For cancer diagnosis, experienced CLE urologists had substantial agreement for both CLE and WLC+CLE (90%, κ 0.80) compared with moderate agreement for WLC alone (74%, κ 0.46), while novice CLE urologists had moderate agreement for CLE (77%, κ 0.55), WLC (78%, κ 0.54), and WLC+CLE (80%, κ 0.59). Pathologists had substantial agreement for CLE (81%, κ 0.61), and nonclinical researchers had moderate agreement (77%, κ 0.49) in cancer diagnosis. For cancer grading, experienced CLE urologists had fair to moderate agreement for CLE (68%, κ 0.64), WLC (74%, κ 0.67), and WLC+CLE (53%, κ 0.33), as did novice CLE urologists for CLE (53%, κ 0.39), WLC (66%, κ 0.50), and WLC+CLE (61%, κ 0.49). Pathologists (65%, κ 0.55) and nonclinical researchers (61%, κ 0.56) both had moderate agreement for CLE in cancer grading. Conclusions CLE is an adoptable technology for cancer diagnosis in novice CLE observers after a short training with moderate interobserver agreement and diagnostic accuracy similar to WLC alone. Experienced CLE observers may be capable of achieving substantial levels of agreement for cancer diagnosis that is higher than with WLC alone. PMID:23072435

  11. Sexual Agreements among Gay Male Couples

    PubMed Central

    Hoff, Colleen H.; Beougher, Sean C.

    2009-01-01

    Many gay male couples make agreements about whether or not to permit sex with outside partners, yet little is known about the development and maintenance of these agreements, their impact on relationships, and whether they are an effective HIV prevention strategy. Using semi-structured, qualitative interviews, 39 gay male couples were asked about their sexual agreements and about other relationship dynamics that might affect their agreements. Analysis revealed a wide range of agreement types, all of which are presented along a continuum rather than as discrete categories. For couples with open agreements, most placed rules or conditions limiting when, where, how often, and with whom outside sex was permitted. Although motivations for having agreements varied, HIV prevention did not rank as a primary factor for any couple. Most couples had congruous agreements; however, a small number reported discrepancies which may increase HIV transmission risk. How couples handled breaks in their agreements also varied, depending on what condition was broken, whether it was disclosed, and the partner's reaction. Additional results include differences in agreement type and motivations for having an agreement based on couple serostatus. Overall, agreements benefited couples by providing boundaries for the relationship, supporting a non-heteronormative identity, and fulfilling the sexual needs of the couple. Future prevention efforts involving gay couples must address the range of agreement types and the meanings couples ascribe to them, in addition to tempering safety messages with the relationship issues that are important to and faced by gay couples. PMID:18686027

  12. 22 CFR 124.1 - Manufacturing license agreements and technical assistance agreements.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Manufacturing license agreements and technical... ARMS REGULATIONS AGREEMENTS, OFF-SHORE PROCUREMENT AND OTHER DEFENSE SERVICES § 124.1 Manufacturing... manufacturing license agreements, technical assistance agreements, distribution agreements, or...

  13. 22 CFR 124.1 - Manufacturing license agreements and technical assistance agreements.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Manufacturing license agreements and technical... ARMS REGULATIONS AGREEMENTS, OFF-SHORE PROCUREMENT AND OTHER DEFENSE SERVICES § 124.1 Manufacturing... manufacturing license agreements, technical assistance agreements, distribution agreements, or...

  14. 22 CFR 124.1 - Manufacturing license agreements and technical assistance agreements.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Manufacturing license agreements and technical... ARMS REGULATIONS AGREEMENTS, OFF-SHORE PROCUREMENT, AND OTHER DEFENSE SERVICES § 124.1 Manufacturing... manufacturing license agreements, technical assistance agreements, distribution agreements, or...

  15. 22 CFR 124.1 - Manufacturing license agreements and technical assistance agreements.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Manufacturing license agreements and technical... ARMS REGULATIONS AGREEMENTS, OFF-SHORE PROCUREMENT AND OTHER DEFENSE SERVICES § 124.1 Manufacturing... manufacturing license agreements, technical assistance agreements, distribution agreements, or...

  16. 22 CFR 124.1 - Manufacturing license agreements and technical assistance agreements.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Manufacturing license agreements and technical... ARMS REGULATIONS AGREEMENTS, OFF-SHORE PROCUREMENT AND OTHER DEFENSE SERVICES § 124.1 Manufacturing... manufacturing license agreements, technical assistance agreements, distribution agreements, or...

  17. Perceptions of patient provider agreements

    PubMed Central

    Albrecht, Jennifer S.; Khokhar, Bilal; Pradel, Françoise; Campbell, Michelle; Palmer, Jacqueline; Harris, Ilene; Palumbo, Francis

    2016-01-01

    Objectives Use of patient provider agreements (PPAs) is increasing, yet there is limited evidence on the effectiveness of PPAs to prevent prescription opioid misuse and diversion, and few guidelines for providers. We conducted eight focus groups to understand patient and prescriber perceptions of PPAs. Methods We recruited 40 patients who had been asked to sign a PPA and 40 prescribers who had administered at least one PPA. We developed topic guides for the two groups based on prior literature. Focus groups were audio-recorded and transcribed verbatim. Two investigators independently performed the content analysis of the transcripts and reached consensus on recurring themes. Key findings PPA use varied according to physician specialty. General practitioners used PPAs the least but reported increasing pressure from liability insurers to use them. Many patients reported signing a PPA in the emergency room of a hospital. Prescribers and patients reported a lack of understanding among patients concerning the purpose and content of the PPA. Prescribers questioned the legal status of the PPA, while patients believed that the PPA was a legal document intended to protect prescribers. Patients and prescribers valued PPA content items differently, although both groups agreed that signing a PPA would not prevent opioid misuse. Conclusions We identified several themes concerning the administration, content, effectiveness and utility of PPAs that highlight areas of research to improve PPAs. We also describe trends requiring further investigation. Understanding content of importance to patients will facilitate the development of a patient-centred PPA. PMID:27293486

  18. Monitoring of Biomedical License Agreements

    PubMed Central

    Keller, George H.; Ferguson, Steven M.; Pan, Percy

    2009-01-01

    Because technology licensed from research organizations can play a significant role in drug innovation and the generation of novel biomedical products, licensee performance under such agreements must be effectively monitored. This is necessary so that resultant benefits, including public health improvement, may be returned to the innovator(s) as well as society at large. The tasks that comprise monitoring are varied, but all come under the general heading of ‘enforcement of license provisions’. Since 1996, the license monitoring and enforcement program established by the US National Institutes of Health (NIH) Group has collected about $US17 million in unpaid and underpaid license royalties through formal financial audits and other investigative activities. During the same period, the Office of Technology Transfer (OTT) settled more than 60 cases of suspected patent infringement, generating around 60 new licenses and collected both back and ongoing royalties. As these numbers show, an active and effective monitoring program is an essential part of any technology transfer or biomedical licensing program. PMID:19960074

  19. The complete exon-intron structure of the 156-kb human gene NFKB1, which encodes the p105 and p50 proteins of transcription factors NF-{kappa}B and I{kappa}B-{gamma}: Implications for NF-{kappa}B-mediated signal transduction

    SciTech Connect

    Heron, E.; Deloukas, P.; van Loon, A.P.G.M.

    1995-12-10

    The NFKB1 gene encodes three proteins of the NF-{kappa}/Rel and I{kappa}B families: p105, p50, and (in mouse) I{kappa}B-{gamma}. We determined the complete genomic structure of human NFKB1. NFKB1 spans 156 kb and has 24 exons with introns varying between 40,000 and 323 bp in length. Although NFKB2, which encodes p100 and p52, also has 24 exons and has a comparable exon-intron structure, it is 20 times shorter than NFKB1. We propose that the long size of NFKB1 is important for transient activation of NF-{kappa}B complexes containing p50. I{kappa}B-{gamma} corresponds to the carboxyl-terminal half of p105. DNA sequence analysis showed that the 3{prime}-end of human intron 11 and the 5{prime}-end of exon 12 of NFKB1 are colinear with the 5{prime}-untranslated region of mouse I{kappa}B-{gamma} cDNA. I{kappa}B-{gamma} is thus likely to be generated by transcription starting within intron 11 and not by alternative splicing of the mouse mRNA encoding p105 and p50. 71 refs., 5 figs., 1 tab.

  20. 14 CFR 437.35 - Agreements.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... TRANSPORTATION LICENSING EXPERIMENTAL PERMITS Requirements to Obtain an Experimental Permit Operational Safety Documentation § 437.35 Agreements. An applicant must enter into the agreements required by § 437.63, and...

  1. 14 CFR 437.35 - Agreements.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... TRANSPORTATION LICENSING EXPERIMENTAL PERMITS Requirements to Obtain an Experimental Permit Operational Safety Documentation § 437.35 Agreements. An applicant must enter into the agreements required by § 437.63, and...

  2. 75 FR 61757 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-06

    ....: 012071-001. Title: APL/Hanjin Reciprocal Space Charter Agreement. Parties: American President Lines, Ltd... Agreement. Parties: Eagle Marine Services, Ltd.; Ports of America Outer Harbor Terminal, LLC; Port...

  3. 75 FR 150 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-04

    ... the members to address issues relating to environmental initiatives and the reduction of air and water pollution. Agreement No.: 012008-004. Title: The 360 Quality Association Agreement. Parties: NYKCool AB...

  4. 76 FR 12962 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-09

    ....gov . Agreement No.: 011885-002. Title: CMA CGM/MSC Reciprocal Space Charter, Sailing and Cooperative... Coast Two-Loop Space Charter, Sailing and Cooperative Working Agreement. Parties: A.P. Moller-Maersk...

  5. 37 CFR 42.409 - Settlement agreements.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... OF COMMERCE TRIAL PRACTICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Derivation After Institution of Derivation Proceeding § 42.409 Settlement agreements. An agreement or understanding under 35 U.S.C. 135(e)...

  6. 75 FR 31438 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-03

    ... Lines Joint Service Agreement. Filing Party: Tara L. Leiter, Esq.; Blank Rome, LLP; Watergate; 600 New... Service Agreement. Filing Party: Tara L. Leiter, Esq.; Blank Rome, LLP; Watergate; 600 New...

  7. 47 CFR 51.303 - Preexisting agreements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) INTERCONNECTION... interconnection agreements between an incumbent LEC and a telecommunications carrier, including those negotiated... approval pursuant to section 252(e) of the Act. (b) Interconnection agreements negotiated before February...

  8. 77 FR 71001 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-28

    ..., updates both parties address, and various other changes. Agreement No.: 012187-000. Title: Siem Car Carrier Pacific AS/Hoegh Autoliners, Inc. Space Charter Agreement. Parties: Siem Car Carrier Pacific...

  9. 32 CFR 37.1260 - Cooperative agreement.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS Definitions of Terms Used in This Part § 37.1260 Cooperative... the cooperative agreement. The term does not include “cooperative research and development...

  10. 77 FR 1689 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-11

    ... . Agreement No.: 012150. Title: COSCON/POS Space Charter and Sailing Agreement. Parties: COSCO Container Lines... COSCO to charter space to Hainan POS in the trade between U.S. West Coast ports and ports in China...

  11. 75 FR 20849 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-21

    .... Agreement No.: 011075-073. Title: Central America Discussion Agreement. Parties: APL Co. PTE Ltd.; Crowley Latin America Services, LLC.; Dole Ocean Cargo Express; Great White Fleet; King Ocean Services...

  12. Upregulation of the kappa opioidergic system in left ventricular rat myocardium in response to volume overload: Adaptive changes of the cardiac kappa opioid system in heart failure.

    PubMed

    Treskatsch, Sascha; Shaqura, Mohammed; Dehe, Lukas; Feldheiser, Aarne; Roepke, Torsten K; Shakibaei, Mehdi; Spies, Claudia D; Schäfer, Michael; Mousa, Shaaban A

    2015-12-01

    Opioids have long been known for their analgesic effects and are therefore widely used in anesthesia and intensive care medicine. However, in the last decade research has focused on the opioidergic influence on cardiovascular function. This project thus aimed to detect the precise cellular localization of kappa opioid receptors (KOR) in left ventricular cardiomyocytes and to investigate putative changes in KOR and its endogenous ligand precursor peptide prodynorphin (PDYN) in response to heart failure. After IRB approval, heart failure was induced using a modified infrarenal aortocaval fistula (ACF) in male Wistar rats. All rats of the control and ACF group were characterized by their morphometrics and hemodynamics. In addition, the existence and localization as well as adaptive changes of KOR and PDYN were investigated using radioligand binding, double immunofluorescence confocal analysis, RT-PCR and Western blot. Similar to the brain and spinal cord, [(3)H]U-69593 KOR selective binding sites were detected the left ventricle (LV). KOR colocalized with Cav1.2 of the outer plasma membrane and invaginated T-tubules and intracellular with the ryanodine receptor of the sarcoplasmatic reticulum. Interestingly, KOR could also be detected in mitochondria of rat LV cardiomyocytes. As a consequence of heart failure, KOR and PDYN were up-regulated on the mRNA and protein level in the LV. These findings suggest that the cardiac kappa opioidergic system might modulate rat cardiomyocyte function during heart failure.

  13. Catena-poly[[bis(hexafluoroacetylacetonato-kappa2O,O')zinc(II)]-micro-4,4'-bipyridine-kappa2N:N'].

    PubMed

    Granifo, Juan; Garland, María Teresa; Baggio, Ricardo

    2004-02-01

    The structure of the title compound, catena-poly[[bis(1,1,1,5,5,5-hexafluoropentane-2,4-dionato-kappa(2)O,O')zinc(III)]-micro-4,4'-bipyridine-kappa(2)N:N'], [Zn(C(5)HF(6)O(2))(2)(C(10)H(8)N(2))](n), consists of polymeric chains, running in two perpendicular directions, organized as planes normal to the tetragonal axis. The elemental unit of the chains is the zinc(II) coordination polyhedron bisected by a twofold symmetry axis, and thus only half of the unit is independent. The octahedral coordination geometry of the metal centre is composed of two oxygen-chelating (symmetry-related) hexafluoroacetylacetonate groups and two translationally related 4,4'-bipyridine groups, which act as connecting agents in the polymer structure. The stabilization of this architecture of chains and planes is associated with a number of weak C-H.O and C-H.F hydrogen bonds. PMID:14767126

  14. Legal issues critical in software license agreements.

    PubMed

    Manfredi, M J; Peterson, D M

    1989-05-01

    The complex legal aspects of software license agreements are addressed in this final part of a three-part series. A healthcare organization that has selected a software vendor and has reviewed the central provisions of a licensing agreement must then take a close look at the other provisions of the agreement. These include numerous legal provisions, regulatory requirements, and ancillary agreements related to maintenance and access to the software.

  15. The role of nuclear factor-kappa B in bacterial translocation in cholestatic rats.

    PubMed

    Weber-Mzell, D; Zaupa, P; Petnehazy, T; Kobayashi, H; Schimpl, G; Feierl, G; Kotanko, P; Höllwarth, M

    2006-01-01

    Xanthinoxidase (XO) derived radical species are involved in bacterial translocation (BT) in cholestatic rats. The mechanism by which XO influences remains unclear. It has been shown recently that nuclear factor-kappa B (NF-kappaB), a ubiquitous transcription factor, can be activated by oxidative stress and thereby promote the process of BT. We investigated the effects of NF-kappaB inactivation on the incidence of BT in cholestatic rats. Sprague-Dawley rats were randomly assigned to one of eight groups: groups 1-4 were sham laparotomized rats either untreated (S1) or treated for 5 days with thalidomide (S2), curcumin (S3), or Inchin-ko (ICK; S4); groups 5-8 underwent common bile duct ligation (CBDL) for 5 days and were either untreated (C1) or treated with thalidomide (C2), curcumin (C3), or ICK (C4). After 5 days bacteriological cultures were performed from portal blood and V. cava, from the central mesenteric lymph node complex (MLN), spleen, and liver. The intensity of the activated NF-kappaB-subunit p65/p50 in the ileum mucosa was estimated by light microscopy and a scoring system from 1 to 20. Malondialdehyde (MDA) and myeloperoxidase activity (MPO) in the ileum were evaluated and expressed as U/g dry weight. Thalidomide and ICK reduced in CBDL-rats significantly the BT rate (63% vs. 18%, 63% vs. 30%, P<0.01). Enzyme estimations (MDA, MPO, and GSH) in sham operated animals showed no significant changes in the untreated groups compared with the treated groups. CBDL-rats pre-treatment with all three compounds caused a significant increase of MDA levels if groups were compared with the untreated C1-group (C1 31.6+/-7.7, C2 54.5+/-12.2, C3 53.3+/-11.2, and C4 47.2+/-9.4). GSH was reduced after the pre-treatment by all compounds but only significantly after curcumin pre-treatment (C1 vs. C3: 13.9+/-1.8 vs. 7.1+/-1.8; P<0.05). MPO estimations were significantly higher in the untreated C1-group if compared with groups C2, C3, and C4 (C1 1036.4+/-340.9, C2 709

  16. {kappa}-Minkowski spacetime as the result of Jordanian twist deformation

    SciTech Connect

    Borowiec, A.; Pachol, A.

    2009-02-15

    Two one-parameter families of twists providing {kappa}-Minkowski * product deformed spacetime are considered: Abelian and Jordanian. We compare the derivation of quantum Minkowski space from two perspectives. The first one is the Hopf module algebra point of view, which is strictly related with Drinfeld's twisting tensor technique. The other one relies on an appropriate extension of ''deformed realizations'' of nondeformed Lorentz algebra by the quantum Minkowski algebra. This extension turns out to be de Sitter Lie algebra. We show the way both approaches are related. The second path allows us to calculate deformed dispersion relations for toy models ensuing from different twist parameters. In the Abelian case, one recovers {kappa}-Poincare dispersion relations having numerous applications in doubly special relativity. Jordanian twists provide a new type of dispersion relations which in the minimal case (related to Weyl-Poincare algebra) takes an energy-dependent linear mass deformation form.

  17. Modelling of Swelling by the Fluorescence Technique in Kappa Carrageenan Gels

    NASA Astrophysics Data System (ADS)

    Tari, Ozlem; Pekcan, Onder

    2011-12-01

    Kappa (-κ) carrageenan gels prepared with various carrageenan concentrations in pure water were completely dried and then swelled in water vapor. Steady state fluorescence measurements were performed using a spectrometer equipped with temperature controller. Pyranine was embedded in κ-carrageenan gels as a fluorescence probe during gel preparation. The fluorescence intensity, I, increased exponentially as swelling time is increased for all gel samples. The increase in I was modelled using Li-Tanaka equation from which swelling time constants, τc and cooperative diffusion coefficients, Dc were determined. It was observed that Dc increased as the swelling temperature was increased. On the other hand at each temperature, it was seen that Dc decreased as kappa carrageenan concentration was increased. Activation energies for swelling were obtained and found to be 57.4, 58.3 and 62.73 kJ mol-1 for the gels with increasing amount of κ-carrageenan content.

  18. AA-negative and Kappa-positive Amyloidosis in a Patient with Rheumatoid Arthritis.

    PubMed

    Ueno, Toshiharu; Sumida, Keiichi; Hoshino, Junichi; Suwabe, Tatsuya; Mise, Koki; Hazue, Ryo; Hayami, Noriko; Hiramatsu, Rikako; Kawada, Masahiro; Imafuku, Aya; Hasegawa, Eiko; Sawa, Naoki; Takaichi, Kenmei; Kinowaki, Keiichi; Ohashi, Kenichi; Fujii, Takeshi; Nishida, Aya; Ubara, Yoshifumi

    2016-01-01

    A 57-year-old Japanese woman with a 5-year history of rheumatoid arthritis (RA) was admitted to our hospital for an evaluation of nephrotic range proteinuria (4.8 g/day). A renal biopsy led to the diagnosis of amyloidosis according to strong positivity for Congo red staining and the detection of microfibrillar structures on electron microscopy that were negative for AA and positive for kappa light chain. Combination therapy with high-dose melphalan and autologous stem cell transplantation was performed according to the regimen for AL amyloidosis. Her proteinuria and RA subsided, but relapsed after 3 years. This is the first report regarding kappa light chain amyloidosis in an RA patient. PMID:27580556

  19. Ion acoustic solitons in a solar wind magnetoplasma with Kappa distributed electrons

    NASA Astrophysics Data System (ADS)

    Devanandhan, Selvaraj; Singh, Satyavir; Singh Lakhina, Gurbax; Sreeraj, T.

    2016-07-01

    In many space plasma environments, the velocity distribution of particles often deviates from Maxwellian and is well-modelled by a kappa distribution function. We have analyzed the ion acoustic soliton in a magnetized consisting of plasma Protons, Helium ions, an electron beam and superthermal hot electrons following kappa distribution function. Under the assumption of weak nonlinearity, the ion-acoustic solitons are described by the Korteweg-de-Vries-Zakharov-Kuznetsov (KdV-ZK) equation. The solution of KdV-ZK equation is used to model the characteristics of the ion acoustic solitary waves in a solar wind magnetoplasma observed at 1 AU. We have found both slow and fast ion acoustic solitons in our study. It is found that the superthermality of hot electrons greatly influence the existence regime of the solitary waves. The numerical results of this study to explain solar wind observations will be discussed in detail.

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

    SciTech Connect

    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 numerical 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.