Sample records for agreement weighted kappa

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

ERIC Educational Resources Information Center

Schuster, Christof

2004-01-01

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

2. 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…

3. A Note on the Linearly and Quadratically Weighted Kappa Coefficients.

PubMed

Li, Pingke

2016-09-01

The linearly and quadratically weighted kappa coefficients are popular statistics in measuring inter-rater agreement on an ordinal scale. It has been recently demonstrated that the linearly weighted kappa is a weighted average of the kappa coefficients of the embedded 2 by 2 agreement matrices, while the quadratically weighted kappa is insensitive to the agreement matrices that are row or column reflection symmetric. A rank-one matrix decomposition approach to the weighting schemes is presented in this note such that these phenomena can be demonstrated in a concise manner. PMID:27246436

4. 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…

5. Kappa coefficient: a popular measure of rater agreement

PubMed Central

TANG, Wan; HU, Jun; ZHANG, Hui; WU, Pan; HE, Hua

2015-01-01

Summary In mental health and psychosocial studies it is often necessary to report on the between-rater agreement of measures used in the study. This paper discusses the concept of agreement, highlighting its fundamental difference from correlation. Several examples demonstrate how to compute the kappa coefficient – a popular statistic for measuring agreement – both by hand and by using statistical software packages such as SAS and SPSS. Real study data are used to illustrate how to use and interpret this coefficient in clinical research and practice. The article concludes with a discussion of the limitations of the coefficient. PMID:25852260

6. Kappa coefficient: a popular measure of rater agreement.

PubMed

Tang, Wan; Hu, Jun; Zhang, Hui; Wu, Pan; He, Hua

2015-02-25

In mental health and psychosocial studies it is often necessary to report on the between-rater agreement of measures used in the study. This paper discusses the concept of agreement, highlighting its fundamental difference from correlation. Several examples demonstrate how to compute the kappa coefficient - a popular statistic for measuring agreement - both by hand and by using statistical software packages such as SAS and SPSS. Real study data are used to illustrate how to use and interpret this coefficient in clinical research and practice. The article concludes with a discussion of the limitations of the coefficient. PMID:25852260

7. A Generalization of Cohen's Kappa Agreement Measure to Interval Measurement and Multiple Raters.

ERIC Educational Resources Information Center

Berry, Kenneth J.; Mielke, Paul W., Jr.

1988-01-01

Cohen's kappa statistic is frequently used to measure agreement between two observers using categorical polytomies. Cohen's statistic is: shown to be inherently multivariate in nature; expanded to analyze ordinal and interval data; and extended to over two observers. A non-asymptotic test of significance is provided for the generalized statistic.…

8. 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

9. 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

10. Weighting the Weights: Agreement among Anthropometric Indicators Identifying the Weight Status of People with Intellectual Disabilities

ERIC Educational Resources Information Center

Verstraelen, C. J. F.; Maaskant, M. A.; van Knijff-Raeven, A. G. M.; Curfs, L. M. G.; van Schrojenstein Lantman-de Valk, H. M. J.

2009-01-01

Background: The aims of this study were (1) to determine to what extent body mass index (BMI), waist circumference, fat free mass index (FFMI) and skinfold thickness are feasible measurement options in people with intellectual disabilities (ID) to measure their weight status, and (2) to assess the level of agreement among these methods. Methods:…

11. 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)

12. 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

13. Agreement between Two Independent Groups of Raters

ERIC Educational Resources Information Center

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…

14. Agreement between routine and research measurement of infant height and weight

PubMed Central

Bryant, M; Santorelli, G; Fairley, L; Petherick, E S; Bhopal, R; Lawlor, D A; Tilling, K; Howe, L D; Farrar, D; Cameron, N; Mohammed, M; Wright, J

2015-01-01

In many countries, routine data relating to growth of infants are collected as a means of tracking health and illness up to school age. These have potential to be used in research. For health monitoring and research, data should be accurate and reliable. This study aimed to determine the agreement between length/height and weight measurements from routine infant records and researcher-collected data. Methods Height/length and weight at ages 6, 12 and 24 months from the longitudinal UK birth cohort (born in Bradford; n=836–1280) were compared with routine data collected by health visitors within 2 months of the research data (n=104–573 for different comparisons). Data were age adjusted and compared using Bland Altman plots. Results There was agreement between data sources, albeit weaker for height than for weight. Routine data tended to underestimate length/height at 6 months (0.5 cm (95% CI −4.0 to 4.9)) and overestimate it at 12 (−0.3 cm (95% CI −0.5 to 4.0)) and 24 months (0.3 cm (95% CI −4.0 to 3.4)). Routine data slightly overestimated weight at all three ages (range −0.04 kg (95% CI −1.2 to 0.9) to −0.04 (95% CI −0.7 to 0.6)). Limits of agreement were wide, particularly for height. Differences were generally random, although routine data tended to underestimate length in taller infants and underestimate weight in lighter infants. Conclusions Routine data can provide an accurate and feasible method of data collection for research, though wide limits of agreement between data sources may be observed. Differences could be due to methodological issues; but may relate to variability in clinical practice. Continued provision of appropriate training and assessment is essential for health professionals responsible for collecting routine data. PMID:25266076

15. Homogeneity of kappa statistics in multiple samples.

PubMed

Reed, J F

2000-08-01

The measurement of intra-observer agreement when the data are categorical has been the subject of several investigators since Cohen first proposed the kappa (kappa) as a chance-corrected coefficient of agreement for nominal scales. Subsequent procedures have been developed to assess the agreement of several raters using a dichotomous classification scheme, assess majority agreement among several raters using a polytomous classification scheme, and the use of kappa as an indicator of the quality of a measurement. Further developments include inference procedures for testing the homogeneity of k>/=2 independent kappa statistics. An executable FORTRAN code for testing the homogeneity of kappa statistics (kappa(h)) across multiple sites or studies is given. The FORTRAN program listing and/or executable programs are available from the author on request. PMID:10927153

16. Single leg mini squat: an inter-tester reproducibility study of children in the age of 9–10 and 12–14 years presented by various methods of kappa calculation

PubMed Central

2012-01-01

Background Multiple studies suggest that reduced postural orientation is a possible risk factor for both patello-femoral joint pain (PFP) and rupture of the anterior cruciate ligament (ACL). In order to prevent PFP and ACL injuries in adolescent athletes, it is necessary to develop simple and predictive screening tests to identify those at high risk. Single Leg Mini Squat (SLMS) is a functional and dynamic real-time screening test, which has shown good validity and reproducibility in evaluation of postural orientation of the knee in an adult population. The aim of this study was to determine the inter-tester reproducibility of SLMS in the age group of 9–10 and 12–14 years by evaluating postural orientation of the ankle, knee, hip and trunk. Further on, this study exemplify the divergence of kappa values when using different methods of calculating kappa for the same dataset. Methods A total of 72 non-injured children were included in the study. Postural orientation of the ankle, knee, hip and trunk for both legs was determined by two testers using a four-point scale (ordinal, 0–3). Prevalence, overall agreement as well as four different methods for calculating kappa were evaluated: linear weighted kappa in comparison with un-weighted kappa, prevalence-adjusted bias-adjusted kappa (PABAK) and quadratic weighted kappa. Results The linear weighted kappa values ranged between 0.54-0.86 (overall agreement 0.86-0.97), reflecting a moderate to almost perfect agreement. When calculating un-weighted kappa (with and without PABAK) and quadratic weighted kappa, the results spread between 0.46-0.88, 0.50-0.94, and 0.76-0.95, reflecting the various results when using different methods of kappa calculation. Conclusions The Single Leg Mini Squat test has moderate to almost perfect reproducibility in children aged 9–10 and 12–14 years when evaluating postural orientation of the ankles, knees, hips and trunk, based on the excellent strength of agreement as presented by

17. 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…

18. Free-Marginal Multirater Kappa (multirater K[free]): An Alternative to Fleiss' Fixed-Marginal Multirater Kappa

ERIC Educational Resources Information Center

Randolph, Justus J.

2005-01-01

Fleiss' popular multirater kappa is known to be influenced by prevalence and bias, which can lead to the paradox of high agreement but low kappa. It also assumes that raters are restricted in how they can distribute cases across categories, which is not a typical feature of many agreement studies. In this article, a free-marginal, multirater…

19. Coronal Diffusion-weighted Magnetic Resonance Imaging of the Kidney: Agreement with Axial Diffusion-weighted Magnetic Imaging in Terms of Apparent Diffusion Coefficient Values

PubMed Central

Wang, Hai-Yi; Wang, Jia; Tang, Ye-Huan; Ye, Hui-Yi; Ma, Lin

2015-01-01

20. 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,…

1. 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

2. KAPPA -- Kernel Application Package

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.

3. 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…

4. 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…

5. Miniaturized kappa goniometer for macromolecular crystallography

SciTech Connect

Rosenbaum, G.; Westbrook, E. M.

1997-07-01

A goniometer with kappa geometry has been designed and built specifically for macromolecular crystallography. The main feature is a miniaturized kappa stage made possible by the small weight of specimen and specimen holder. The design goal was to: 1) eliminate interference between stage and area detector for specimen-to-detector distances of 100 mm and more; 2) minimize the sphere of confusion on expectation of dealing with very small crystals at third generation sources; 3) minimize the solid angle of shadow and inaccessible positioning of the sample due to interference of the stage with other objects in the sample area; 4) achieve a rotation speed of 10 degree/s at 0.5% constancy and 0.4 s acceleration time for 0.05 s exposures of 0.2 degree fine slice frames every 2 seconds, and 5) to achieve precise synchronization between rotation angle and shutter opening and closing. The kappa stage is mounted on a commercial high precision rotary table, designed for use in both horizontal and vertical orientation. This table provides the high precision rotation for data acquisition. The required crisp response and constant speed is delivered by a high output direct drive DC-motor, controlled by a closed-loop controller using feedback from a precision angular encoder. The kappa- and phi-motions are used for sample positioning only and are driven by miniature DC-motors equipped with integral encoders.

6. Miniaturized kappa goniometer for macromolecular crystallography

SciTech Connect

Rosenbaum, G.; Westbrook, E.M.

1997-07-01

A goniometer with kappa geometry has been designed and built specifically for macromolecular crystallography. The main feature is a miniaturized kappa stage made possible by the small weight of specimen and specimen holder. The design goal was to: 1) eliminate interference between stage and area detector for specimen-to-detector distances of 100 mm and more; 2) minimize the sphere of confusion on expectation of dealing with very small crystals at third generation sources; 3) minimize the solid angle of shadow and inaccessible positioning of the sample due to interference of the stage with other objects in the sample area; 4) achieve a rotation speed of 10 degree/s at 0.5{percent} constancy and 0.4 s acceleration time for 0.05 s exposures of 0.2 degree fine slice frames every 2 seconds, and 5) to achieve precise synchronization between rotation angle and shutter opening and closing. The kappa stage is mounted on a commercial high precision rotary table, designed for use in both horizontal and vertical orientation. This table provides the high precision rotation for data acquisition. The required crisp response and constant speed is delivered by a high output direct drive DC-motor, controlled by a closed-loop controller using feedback from a precision angular encoder. The kappa- and phi-motions are used for sample positioning only and are driven by miniature DC-motors equipped with integral encoders.{copyright} {ital 1997 American Institute of Physics.}

7. Intra- and interobserver agreement on the Oestern and Tscherne classification of soft tissue injury in periarticular lower-limb closed fractures

PubMed Central

Estrada-Castrillón, Mauricio; Hincapie, Jorge Andrés; Lugo-Agudelo, Luz Helena

2014-01-01

Background: The soft tissues injury in periarticular fractures of the lower extremities determines the proper time to perform bone fixation. Objective: The aim of this study was to determine the intra and interobserver agreement in the Tscherne classification. Methods: This is a descriptive, prospective study for patients admitted to the Pablo Tobón Uribe Hospital (PTUH) with tibial plateau or tibial pilon fractures. We performed a standardize evaluation using video photography at the time of admission and 24, 48, and 72 h after admission. Fifteen five reviewers who had various levels of training produced a total of 1,200 observations. The intra- and interobserver agreement was assessed using a weighted kappa for multiple raters and more than two categories. Results: Twenty patients were admitted with tibial plateau and tibial pilon fractures. The intraobserver agreement for all 15 raters was kappa 0.81 (95% CI 0.79-0.83), and the interobserver agreement for all 15 raters was kappa 0.65 (95% CI 0.55-0.73). The interobserver agreement at 24 h was kappa 0.67 (95% CI 0.46-0.86). Conclusions: Classifying the severity of soft tissue injury is critical in planning the surgical management of fractures of the lower extremities. Based on our results, we can reasonably argue that the Tscherne classification produced an adequate level of agreement and could be used to standardize and to guide the treatment, and to conduct research studies. PMID:25767306

8. 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

9. 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

10. Agreement between self-reported and measured height, weight and body mass index in old age—a longitudinal study with 20 years of follow-up

PubMed Central

Dahl, Anna K.; Hassing, Linda B.; Fransson, Eleonor I.; Pedersen, Nancy L.

2010-01-01

Background: self-reported body mass index (BMI) based on self-reported height and weight is a widely used measure of adiposity in epidemiological research. Knowledge about the accuracy of these measures in late life is scarce. Objective: the study aimed to evaluate the accuracy and changes in accuracy of self-reported height, weight and BMI calculated from self-reported height and weight in late life. Design: a longitudinal population-based study with five times of follow-up was conducted. Participants: seven hundred seventy-four community-living men and women, aged 40–88 at baseline (mean age 63.9), included in The Swedish Adoption/Twin Study of Aging. Methods: participants self-reported their height and weight in a questionnaire, and height and weight were measured by experienced research nurses at an in-person testing five times during a 20-year period. BMI was calculated as weight (kilogramme)/height (metre)2. Results: latent growth curve modelling showed an increase in the mean difference between self-reported and measured values over time for height (0.038 cm/year) and BMI (0.016 kg/m2/year), but not for weight. Conclusions: there is a very small increase in the mean difference between self-reported and measured BMI with ageing, which probably would not affect the results when self-reported BMI is used as a continuous variable in longitudinal studies. PMID:20453247

11. 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.

12. Spontaneous activation of the NF-kappaB signaling pathway in isolated normal glomeruli.

PubMed

Hayakawa, Kunihiro; Meng, Yiman; Hiramatsu, Nobuhiko; Kasai, Ayumi; Yao, Jian; Kitamura, Masanori

2006-12-01

In this report, we describe that NF-kappaB is spontaneously activated in isolated, normal glomeruli. Ex vivo incubation of isolated rat glomeruli triggered expression of a NF-kappaB-dependent gene, monocyte chemoattractant protein-1 (MCP-1), in parallel with downregulation of IkappaBalpha and IkappaBbeta proteins and activation of the p65 NF-kappaB subunit. The induction of MCP-1 was also observed in mesangial cells coincubated with isolated glomeruli or exposed to media conditioned by isolated glomeruli (GCM), which was abrogated by inhibition of NF-kappaB. The activation of NF-kappaB by glomerulus-derived factors was confirmed using reporter mesangial cells that produce secreted alkaline phosphatase (SEAP) under the control of the kappaB enhancer element. When the reporter cells were adoptively transferred into normal glomeruli, expression of SEAP mRNA and activity of SEAP were also upregulated in the explanted glomeruli. The molecular weight of factors responsible for activation of NF-kappaB was >50 kDa, and TNF-alpha was identified as one of glomerulus-derived activators. To examine upstream events involved, we focused on MAP kinases that are spontaneously activated in explanted glomeruli. Selective suppression of ERK or p38 MAP kinase significantly attenuated activation of NF-kappaB in mesangial cells triggered by coculture with isolated glomeruli. Interestingly, the suppressive effects by MAP kinase inhibitors were not observed in mesangial cells treated with GCM. These data suggested that NF-kappaB was spontaneously activated in explanted glomeruli via autocrine/paracrine factors including TNF-alpha and that the production of NF-kappaB activators by glomeruli was, at least in part, through MAP kinase pathways. PMID:16705144

13. Inter-rater agreement and reliability of the COSMIN (COnsensus-based Standards for the selection of health status Measurement Instruments) Checklist

PubMed Central

2010-01-01

Background The COSMIN checklist is a tool for evaluating the methodological quality of studies on measurement properties of health-related patient-reported outcomes. The aim of this study is to determine the inter-rater agreement and reliability of each item score of the COSMIN checklist (n = 114). Methods 75 articles evaluating measurement properties were randomly selected from the bibliographic database compiled by the Patient-Reported Outcome Measurement Group, Oxford, UK. Raters were asked to assess the methodological quality of three articles, using the COSMIN checklist. In a one-way design, percentage agreement and intraclass kappa coefficients or quadratic-weighted kappa coefficients were calculated for each item. Results 88 raters participated. Of the 75 selected articles, 26 articles were rated by four to six participants, and 49 by two or three participants. Overall, percentage agreement was appropriate (68% was above 80% agreement), and the kappa coefficients for the COSMIN items were low (61% was below 0.40, 6% was above 0.75). Reasons for low inter-rater agreement were need for subjective judgement, and accustom to different standards, terminology and definitions. Conclusions Results indicated that raters often choose the same response option, but that it is difficult on item level to distinguish between articles. When using the COSMIN checklist in a systematic review, we recommend getting some training and experience, completing it by two independent raters, and reaching consensus on one final rating. Instructions for using the checklist are improved. PMID:20860789

14. Modeling Plasmas with a Kappa Electron Energy Distribution

Hahn, Michael; Savin, Daniel Wolf

2016-05-01

Nonthermal kappa electron energy distributions have been observed in the Earth's magnetosphere and the solar wind, and are likely also present in the solar corona and in solar flares. In order to model the spectra of these plasmas, it is necessary to obtain the appropriate collision rate coefficients. We show that this can be done simply by summing appropriately weighted Maxwellian rate coefficients. The resulting data have similar or better accuracies than are obtained with other approaches. Summing Maxwellians has the additional advantages of being easy to implement and extendable to many different collision processes. We apply this technique to modeling the charge state distribution (CSD) of kappa-distribution plasmas. In particular, we examine the influence of electron impact multiple ionization on the equilibrium CSD and calculate the time variation of the CSD during a solar flare.

15. Modeling Plasmas with a Kappa Electron Energy Distribution

Hahn, Michael; Savin, Daniel Wolf

2016-06-01

Nonthermal kappa electron energy distributions have been observed in the Earth's magnetosphere and the solar wind, and are likely also present in the solar corona and in solar flares. In order to model the spectra of these plasmas, it is necessary to obtain the appropriate collision rate coefficients. We show that this can be done simply by summing appropriately weighted Maxwellian rate coefficients. The resulting data have similar or better accuracies than are obtained with other approaches. Summing Maxwellians has the additional advantages of being easy to implement and extendable to many different collision processes. We apply this technique to modeling the charge state distribution (CSD) of kappa-distribution plasmas. In particular, we examine the influence of electron impact multiple ionization on the equilibrium CSD and calculate the time variation of the CSD during a solar flare.

16. A Ratio Test of Interrater Agreement with High Specificity

ERIC Educational Resources Information Center

Cousineau, Denis; Laurencelle, Louis

2015-01-01

Existing tests of interrater agreements have high statistical power; however, they lack specificity. If the ratings of the two raters do not show agreement but are not random, the current tests, some of which are based on Cohen's kappa, will often reject the null hypothesis, leading to the wrong conclusion that agreement is present. A new test of…

17. Study of the KAPPA antiKAPPA. pi. final state in J/psi hadronic decays

SciTech Connect

Becker, J.J.; Blaylock, G.T.; Bolton, T.; Brown, J.S.; Bunnell, K.O.; Burnett, T.H.; Cassell, R.E.; Coffman, D.; Cook, V.; Coward, D.H.

1987-02-01

The reactions J/psi ..-->.. ..omega..KAPPA antiKAPPA..pi.. and J/psi ..-->.. phiKAPPA/sup + -/KAPPA/sub S//sup 0/..pi../sup - +/ have been studied using a sample of 5.8 x 10/sup 6/ produced J/psi decays. The KAPPA/sup + -/KAPPA/sub S//sup 0/..pi../sup - +/ and KAPPA/sup +/KAPPA/sup -/..pi../sup 0/ systems recoiling against an ..omega.. show enhancements in the mass distribution around 1.445 GeV/c/sup 2/ with consistent branching ratios. No such structure is observed in the mass distribution of the KAPPA/sup + -/KAPPA/sub S//sup 0/..pi../sup - +/ system recoiling against a phi. A comparison of these observations with the corresponding channels in radiative J/psi decays permits a detailed study of the structures seen in the iota(1440) and EPSILON(1420) signal regions. 8 refs., 4 figs.

18. 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.

19. Differential ontogeny of multiple opioid receptors (mu, delta, and kappa)

SciTech Connect

Spain, J.W.; Roth, B.L.; Coscia, C.J.

1985-03-01

We investigated the postnatal ontogeny of opioid receptors in rat brain under assay conditions which, when combined with computerized analysis, effectively reflect the developmental profile of high affinity binding to mu, delta, and kappa subpopulations. Concentrations of mu sites were assessed with the selective ligand /sup 3/H-(D-ala2,mePhe4,gly-ol5)enkephalin (DAGO). The other two sites were analyzed in binding assays with less selective radioligands but in the presence of specific unlabeled ligands which suppress cross-reactivity. We utilized /sup 3/H-(D-ala2,D-leu5)enkephalin (DADL) in the presence of 10 nM DAGO to label delta sites and /sup 3/H-ethylketocyclazocine (EKC) in the presence of 100 nM DADL + 100 nM (D-ala2,mePhe4,Met(0)ol5)enkephalin to detect kappa receptors. After birth, the density (femtomoles per milligram of wet weight) of mu sites declined for several days and then rose sharply over the next 2 weeks, increasing 2-fold by adulthood. Delta (delta) sites appeared in the second week postnatal and increased more than 8-fold in the next 2 weeks. Levels of kappa receptors were relatively low at birth and increased slowly (2-fold, overall). Computerized analyses of binding data revealed that DAGO and DADL were binding to single populations of sites throughout the postnatal period. DAGO and EKC affinities did not fluctuate in this period, whereas DADL affinities were low for the first week and then rose to adult levels. In summary, mu, kappa, and delta receptors exhibit differential postnatal developmental profiles. The former two are present at birth, whereas the latter appears in the second week. The postnatal increase for all three sites appear to be preceded by the previously demonstrated emergence of opioid peptides.

20. 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

1. 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

2. Agreement Analysis among Measures of Thinness and Obesity Assessment in Iranian School Children and Adolescents

PubMed Central

Ayatollahi, Seyyed-Mohammad-Taghi; Bagheri, Zahra; Heydari, Seyyed-Taghi

2013-01-01

Purpose This study investigated the agreement of four anthropometric-based measurements including weight-for-height (WH), body mass index-for-age (BMI), mid-upper arm circumference-for-age (MUAC) and triceps skinfold thickness-for-age (TST) to identify underweight and overweight children and adolescents. Methods Two data sets were used in this research. The first one was a multistage random sample of 2397 healthy school children in pre-pubertal stage in Shiraz. The second data set consisted of 487 healthy students in pubertal stage and 558 students in post-pubertal stage. The parametric LMS method was used to construct reference centiles curves for each measure. The Kappa statistic was applied to examine the pairwise agreement of the four indices for detecting thinness and obesity. Results Generally, the pairwise agreement of adiposity measures was higher for identifying obesity than thinness. There was an excellent agreement between WH and BMI for detecting both thin and obese children in almost all subgroups (P<0.001). MUAC had an excellent agreement with BMI in pre-pubertal individuals (P<0.001). However, TST had a weak agreement with the other three indices for detecting thinness and weak to good agreement for classification of obesity. Conclusion The performance of the four anthropometric-based measurements varied by sex and maturity level. MUAC as a simple and low-cost screening tool can also be used as an alternative to BMI for obesity assessment among pre-pubertal groups. PMID:24800002

3. Kappa Opioid Receptors on Dopaminergic Neurons Are Necessary for Kappa-Mediated Place Aversion

PubMed Central

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

2013-01-01

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 (DATCre/wt/KORloxp/loxp, or DATCre-KOR KO). In agreement with previous findings, control mice (DATCre/wt/KORwt/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

4. 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.

5. Detection of kappa and lambda light chain monoclonal proteins in human serum: automated immunoassay versus immunofixation electrophoresis.

PubMed

Jaskowski, Troy D; Litwin, Christine M; Hill, Harry R

2006-02-01

Recently, turbidimetric immunoassays for detecting and quantifying kappa and lambda free light chains (FLC) have become available and are promoted as being more sensitive than immunofixation electrophoresis (IFE) in detecting FLC monoclonal proteins. In this study, we assessed the ability of these turbidimetric assays to detect serum monoclonal proteins involving both free and heavy-chain-bound kappa and lambda light chains compared to standard immunofixation electrophoresis. Sera demonstrating a restricted band of protein migration (other than a definite M spike) by serum protein electrophoresis (SPE), which may represent early monoclonal proteins, were also examined. When compared to IFE, percent agreement, sensitivity, and specificity for the kappa-FLC and lambda-FLC were 94.6, 72.9, and 99.5% and 98.5, 91.4, and 99.7%, respectively, in detecting monoclonal proteins involving free and heavy-chain-bound light chains. The majority of sera (73.7%) demonstrating a restricted band of protein migration on SPE demonstrated abnormal IFE patterns suggestive of multiple myeloma or monoclonal gammopathy of unknown significance, but gave normal kappa/lambda FLC ratios using the turbidimetric immunoassays. In conclusion, the kappa and lambda FLC assays are significantly less sensitive (72.9 to 91.4%) than IFE, but specific in detecting serum monoclonal proteins. Moreover, the kappa/lambda ratio has little value in routine screening since the majority of sera with abnormal IFE patterns had normal kappa/lambda FLC ratios. PMID:16467338

6. 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.

7. 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.

8. Kappa Cygnid rate variations over 41 years

Rendtel, J.; Arlt, R.

2016-06-01

Enhanced rates of the kappa Cygnids in 2007 and 2014 had been considered as a hint at periodic rate/flux enhancement. Here we use an extended data set of visual observations covering the 41-year period 1975-2015. Applying a wavelet analysis to the data series yields no periodic ZHR variations in the given period and the optical meteor magnitude range.

9. 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…

10. Rankine-Hugoniot jump conditions incorporating kappa distributions

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.

11. A Simple Method for Modeling Collision Processes in Plasmas with a Kappa Energy Distribution

Hahn, M.; Savin, D. W.

2015-08-01

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.

12. Coupling of a signal response domain in I kappa B alpha to multiple pathways for NF-kappa B activation.

PubMed Central

Brockman, J A; Scherer, D C; McKinsey, T A; Hall, S M; Qi, X; Lee, W Y; Ballard, D W

1995-01-01

The eukaryotic transcription factor NF-kappa B plays a central role in the induced expression of human immunodeficiency virus type 1 and in many aspects of the genetic program mediating normal T-cell activation and growth. The nuclear activity of NF-kappa B is tightly regulated from the cytoplasmic compartment by an inhibitory subunit called I kappa B alpha. This cytoplasmic inhibitor is rapidly phosphorylated and degraded in response to a diverse set of NF-kappa B-inducing agents, including T-cell mitogens, proinflammatory cytokines, and viral transactivators such as the Tax protein of human T-cell leukemia virus type 1. To explore these I kappa B alpha-dependent mechanisms for NF-kappa B induction, we identified novel mutants of I kappa B alpha that uncouple its inhibitory and signal-transducing functions in human T lymphocytes. Specifically, removal of the N-terminal 36 amino acids of I kappa B alpha failed to disrupt its ability to form latent complexes with NF-kappa B in the cytoplasm. However, this deletion mutation prevented the induced phosphorylation, degradative loss, and functional release of I kappa B alpha from NF-kappa B in Tax-expressing cells. Alanine substitutions introduced at two serine residues positioned within this N-terminal regulatory region of I kappa B alpha also yielded constitutive repressors that escaped from Tax-induced turnover and that potently inhibited immune activation pathways for NF-kappa B induction, including those initiated from antigen and cytokine receptors. In contrast, introduction of a phosphoserine mimetic at these sites rectified this functional defect, a finding consistent with a causal linkage between the phosphorylation status and proteolytic stability of this cytoplasmic inhibitor. Together, these in vivo studies define a critical signal response domain in I kappa B alpha that coordinately controls the biologic activities of I kappa B alpha and NF-kappa B in response to viral and immune stimuli. PMID:7739562

13. Sensitivity of Diffusion-Weighted STEAM MRI and EPI-DWI to Infratentorial Ischemic Stroke

PubMed Central

Hohenhaus, Marc; Kunze, Claudia; Schmidt, Wolf; Brunecker, Peter; Villringer, Kersten; Merboldt, Klaus-Dietmar; Frahm, Jens; Fiebach, Jochen B.

2016-01-01

Objectives To assess the sensitivity of stimulated echo acquisition mode diffusion weighted imaging (STEAM-DWI) to ischemic stroke in comparison to echo-planar imaging diffusion weighted imaging (EPI-DWI) in the infratentorial compartment. Methods Fifty-seven patients presenting with clinical features of infratentorial stroke underwent STEAM-DWI, high-resolution EPI-DWI (HR-DWI, 2.5 mm slice thickness) and low-resolution EPI-DWI (LR-DWI, 5 mm slice thickness). Four readers assessed the presence of ischemic lesions and artifacts. Agreement between sequences and interobserver agreement on the presence of ischemia were calculated. The sensitivities of the DWI sequences were calculated in 45 patients with a confirmed diagnosis of infratentorial stroke. Results Median time from symptom onset to imaging was 24 hours. STEAM-DWI agreed with LR-DWI in 89.5% of cases (kappa = 0.72, p<0.0001) and with HR-DWI in 89.5% of cases (kappa = 0.68, p<0.0001). STEAM-DWI showed fewer intraparenchymal artifacts (1/57) than HR-DWI (44/57) and LR-DWI (41/57). Ischemia was visible in 87% of cases for LR-DWI, 93% of cases for HR-DWI, and 89% of cases for STEAM-DWI. Interobserver agreement was good for STEAM-DWI (kappa = 0.62, p<0.0001). Conclusions Compared to the best currently available MR sequence for detecting ischemia (HR-DWI), STEAM-DWI shows fewer artifacts and a similar sensitivity to infratentorial stroke. PMID:27529697

14. 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

15. 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…

16. 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…

17. Reproducibility of Vertebral Fracture Assessment Readings From Dual-energy X-ray Absorptiometry in Both a Population-based and Clinical Cohort: Cohen's and Uniform Kappa.

PubMed

Aubry-Rozier, Bérengère; Chapurlat, Roland; Duboeuf, François; Iglesias, Katia; Krieg, Marc-Antoine; Lamy, Olivier; Burnand, Bernard; Hans, Didier

2015-01-01

Vertebral fracture assessments (VFAs) using dual-energy X-ray absorptiometry increase vertebral fracture detection in clinical practice and are highly reproducible. Measures of reproducibility are dependent on the frequency and distribution of the event. The aim of this study was to compare 2 reproducibility measures, reliability and agreement, in VFA readings in both a population-based and a clinical cohort. We measured agreement and reliability by uniform kappa and Cohen's kappa for vertebral reading and fracture identification: 360 VFAs from a population-based cohort and 85 from a clinical cohort. In the population-based cohort, 12% of vertebrae were unreadable. Vertebral fracture prevalence ranged from 3% to 4%. Inter-reader and intrareader reliability with Cohen's kappa was fair to good (0.35-0.71 and 0.36-0.74, respectively), with good inter-reader and intrareader agreement by uniform kappa (0.74-0.98 and 0.76-0.99, respectively). In the clinical cohort, 15% of vertebrae were unreadable, and vertebral fracture prevalence ranged from 7.6% to 8.1%. Inter-reader reliability was moderate to good (0.43-0.71), and the agreement was good (0.68-0.91). In clinical situations, the levels of reproducibility measured by the 2 kappa statistics are concordant, so that either could be used to measure agreement and reliability. However, if events are rare, as in a population-based cohort, we recommend evaluating reproducibility using the uniform kappa, as Cohen's kappa may be less accurate. PMID:25439454

18. The Placental Distal Villous Hypoplasia Pattern: Interobserver Agreement and Automated Fractal Dimension as an Objective Metric.

PubMed

Mukherjee, Anika; Chan, Adrian D C; Keating, Sarah; Redline, Raymond W; Fritsch, Michael K; Machin, Geoffrey A; Cornejo-Palma, Daniel; de Nanassy, Joseph; El-Demellawy, Dina; von Dadelszen, Peter; Benton, Samantha J; Grynspan, David

2016-01-01

The distal villous hypoplasia (DVH) pattern is a placental correlate of fetal growth restriction. Because the pattern seems to involve less complexity than do appropriately developed placental villi, we postulated that it may be associated with lower fractal dimension-a mathematical measure of complexity. Our study objectives were to evaluate interobserver agreement related to the DVH pattern among expert pathologists and to determine whether pathologist classification of DVH correlates with fractal dimension. A study set of 30 images of placental parenchyma at ×4 magnification was created by a single pathologist from a digital slide archive. The images were graded for the DVH pattern according to pre-specified definitions and included 10 images graded as "no DVH" (grade  =  0), 10 with mild to moderate DVH (grade  =  1), and 10 with severe DVH (grade  =  2). The images were randomly sorted and shown to a panel of 4 international experts who similarly graded the images for DVH. Weighted kappas were calculated. For each image, fractal dimension was calculated by the Box Counting method. The correlation coefficient between (1) the averaged DVH scores obtained by the 5 pathologists and (2) fractal dimension was calculated. The mean weighted kappa score among the observers was 0.59 (range: 0.42-0.70). The correlation coefficient between fractal dimension and the averaged DVH score was -0.915 (P < 0.001). Expert pathologists achieve fair to substantial agreement in grading DVH, indicating consensus on the definition of DVH. Distal villous hypoplasia correlates extremely well with fractal dimension and represents an objective measure for DVH. PMID:26275121

19. 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.

20. Cyclam kappa4 to kappa3 ligand denticity change upon mono-n-substitution with a carboxypropyl pendant arm in a ruthenium nitrosyl complex.

PubMed

Doro, Fábio G; Castellano, Eduardo E; Moraes, Luiz A B; Eberlin, Marcos N; Tfouni, Elia

2008-05-19

The complex fac-[Ru(NO)Cl2(kappa(3)N(4),N(8),N(11)(1-carboxypropyl)cyclam)]Cl.H2O (1-carboxypropyl)cyclam=3-(1,4,8,11-tetraazacyclotetradecan-1-yl)propionic acid) was prepared in a one pot reaction by mixing equimolar amounts of RuNOCl 3 and (1-carboxypropyl)cyclam and was characterized by X-ray crystallography, electrospray ionization tandem mass spectrometry (ESI-MS/MS), elemental analysis, NMR, and electronic and vibrational (IR) spectroscopies. fac-[Ru(NO)Cl 2(kappa(3)N(4),N(8),N(11)(1-carboxypropyl)cyclam)]Cl.H2O crystallizes in the triclinic, space group P1, No. 2, with unit cell parameters of a=8.501(1) A, b=9.157(1) A, c=14.200(1) A, alpha=72.564(5) degrees , beta=82.512(5) degrees , gamma=80.308(5) degrees , and Z=2. The Ru-N interatomic distance and bond angle in the [Ru-NO] unit are 1.739(2) A and 167.7(2) degrees , respectively. ESI-MS/MS shows characteristic dissociation chemistry that initiates by HCl or NO loss. The IR spectrum displays a nu(NO) at 1881 cm(-1) indicating a nitrosonium character. The electronic spectrum shows absorptions bands at 264 nm (log epsilon=3.27), 404 nm (log epsilon=2.53), and 532 nm (log epsilon=1.88). (1)H and (13)C NMR are in agreement with the proposed molecular structure, which shows a very singular architecture where the cyclam ring N (with the carboxypropyl pendant arm) is not coordinated to the ruthenium resulting in a kappa(3) instead of the expected kappa(4) denticity. PMID:18399626

1. Genomic organization and evolution of immunoglobulin kappa gene enhancers and kappa deleting element in mammals

PubMed Central

Das, Sabyasachi; Nikolaidis, Nikolas; Nei, Masatoshi

2009-01-01

We have studied the genomic structure and evolutionary pattern of immunoglobulin kappa deleting element (KDE) and three kappa enhancers (KE5′, KE3′P, and KE3′D) in eleven mammalian genomic sequences. Our results show that the relative positions and the genomic organization of the KDE and the kappa enhancers are conserved in all mammals studied and have not been affected by the local rearrangements in the immunoglobulin kappa (IGK) light chain locus over a long evolutionary time (∼120 million years of mammalian evolution). Our observations suggest that the sequence motifs in these regulatory elements have been conserved by purifying selection to achieve proper regulation of the expression of the IGK light chain genes. The conservation of the three enhancers in all mammals indicates that these species may use similar mechanisms to regulate IGK gene expression. However, some activities of the IGK enhancers might have evolved in the eutherian lineage. The presence of the three IGK enhancers, KDE, and other recombining elements (REs) in all mammals (including platypus) suggest that these genomic elements were in place before the mammalian radiation. PMID:19560204

2. 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

3. Experimental and ab initio infrared study of chi-, kappa- and alpha-aluminas formed from gibbsite

SciTech Connect

Favaro, L.; Boumaza, A.; Roy, P.; Ledion, J.; Sattonnay, G.; Brubach, J.B.; Huntz, A.M.; Tetot, R.

2010-04-15

chi-, kappa- and alpha-alumina phases formed by dehydration of micro-grained gibbsite between 773 and 1573 K are studied using infrared spectroscopy (IR). The structural transitions evidenced by X-ray diffraction (XRD) were interpreted by comparing IR measurements with ab initio simulations (except for the chi form whose complexity does not allow a reliable simulation). For each phase, IR spectrum presents specific bands corresponding to transverse optical (TO) modes of Al-O stretching and bending under 900 cm{sup -1}. The very complex chi phase, obtained at 773 K, provides a distinctive XRD pattern in contrast with the IR absorbance appearing as a broad structure extending between 200 and 900 cm{sup -1} resembling the equivalent spectra for gamma-alumina phase. kappa-alumina is forming at 1173 K and its rich IR spectrum is in good qualitative agreement with ab initio simulations. This complexity reflects the large number of atoms in the kappa-alumina unit cell and the wide range of internuclear distances as well as the various coordinances of both Al and O atoms. Ab initio simulations suggest that this form of transition alumina demonstrates a strong departure from the simple pattern observed for other transition alumina. At 1573 K, the stable alpha-ALPHAl{sub 2}OMICRON{sub 3} develops. Its IR spectra extends in a narrower energy range as compared to transition alumina and presents characteristics features similar to model alpha-ALPHAl{sub 2}OMICRON{sub 3}. Ab initio calculations show again a very good general agreement with the observed IR spectra for this phase. In addition, for both kappa- and alpha-ALPHAl{sub 2}OMICRON{sub 3}, extra modes, measured at high energy (above 790 cm{sup -1} for kappa and above 650 cm{sup -1} for alpha), can originate from either remnant chi-alumina or from surface modes. - Graphical abstract: Infrared spectra of the sequence Gibbsite ->chi->kappa->alpha-Al{sub 2}O{sub 3} obtained from 24 h calcinations of Gibbsite at 773 K, 1173 K

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

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

5. IRF-2 regulates NF-{kappa}B activity by modulating the subcellular localization of NF-{kappa}B

SciTech Connect

Chae, Myounghee; Kim, Kwangsoo; Park, Sun-Mi; Jang, Ik-Soon; Seo, Taegun; Kim, Dong-Min; Kim, Il-Chul; Lee, Je-Ho; Park, Junsoo

2008-06-06

Nuclear Factor-kappa B (NF-{kappa}B) is a transcription factor essential to the control of cell proliferation, survival, differentiation, immune response, and inflammation. Constitutive NF-{kappa}B activation has been observed in a broad variety of solid tumors and hematological malignancies, which suggests that NF-{kappa}B signaling may perform a critical role in the development of human cancers. Interferon regulatory factor-2 (IRF-2), an antagonistic transcriptional repressor of IRF-1, evidences oncogenic potential, but little is currently known regarding the mechanism underlying the oncogenic activities of IRF-2. In this study, we report that IRF-2 recruits RelA/p65 transcription factors into the nucleus via physical interaction. While the nuclear recruitment of RelA by IRF-2 augments TNF{alpha}-induced NF-{kappa}B dependent transcription, the N-terminal truncated mutant form of IRF-2 inhibits the nuclear localization of RelA, and thus interferes with NF-{kappa}B activation. Furthermore, the knockdown of IRF-2 by IRF-2 siRNA attenuates TNF{alpha}-induced NF-{kappa}B dependent transcription by inhibiting the nuclear localization of RelA. Thus, these results show that IRF-2 regulates NF-{kappa}B activity via the modulation of NF-{kappa}B subcellular localization.

6. Agreement, the f-measure, and reliability in information retrieval.

PubMed

2005-01-01

Information retrieval studies that involve searching the Internet or marking phrases usually lack a well-defined number of negative cases. This prevents the use of traditional interrater reliability metrics like the kappa statistic to assess the quality of expert-generated gold standards. Such studies often quantify system performance as precision, recall, and F-measure, or as agreement. It can be shown that the average F-measure among pairs of experts is numerically identical to the average positive specific agreement among experts and that kappa approaches these measures as the number of negative cases grows large. Positive specific agreement-or the equivalent F-measure-may be an appropriate way to quantify interrater reliability and therefore to assess the reliability of a gold standard in these studies. PMID:15684123

7. Asterias rubens: Evidence of NF-kappa B genes.

PubMed

Leclerc, Michel; Kresdorn, Nicolas; Horres, Ralf

2016-06-01

In the present paper we show a survey of the Asterias rubens sea star genome for genes associated with NF-kappa-B proteins implied in the immune response. The NF-kappa B gene, into 2 subunits, was found in this invertebrate. PMID:27014588

8. 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…

9. 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…

10. Origins and properties of kappa distributions in space plasmas

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.

11. 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

12. 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.

13. Deletion of the immunoglobulin kappa chain intron enhancer abolishes kappa chain gene rearrangement in cis but not lambda chain gene rearrangement in trans.

PubMed Central

Takeda, S; Zou, Y R; Bluethmann, H; Kitamura, D; Muller, U; Rajewsky, K

1993-01-01

Immunoglobulins (Ig) secreted from a plasma cell contain either kappa or lambda light chains, but not both. This phenomenon is termed isotypic kappa-lambda exclusion. While kappa-producing cells have their lambda chain genes in germline configuration, in most lambda-producing cells the kappa chain genes are either non-productively rearranged or deleted. To investigate the molecular mechanism for isotypic kappa-lambda exclusion, in particular the role of the Ig kappa intron enhancer, we replaced this enhancer by a neomycin resistance (neoR) gene in embryonic stem (ES) cells. B cells heterozygous for the mutation undergo V kappa-J kappa recombination exclusively in the intact Ig kappa locus but not in the mutated Ig kappa locus. Homozygous mutant mice exhibited no rearrangements in their Ig kappa loci. However, splenic B cell numbers were only slightly reduced as compared with the wild-type, and all B cells expressed lambda chain bearing surface Ig. These findings demonstrate that rearrangement in the Ig kappa locus is not essential for lambda gene rearrangement. We also generated homozygous mutant mice in which the neoR gene was inserted at the 3' end of the Ig kappa intron enhancer. Unexpectedly, mere insertion of the neoR gene showed some suppressive effect on V kappa-J kappa recombination. However, the much more pronounced inhibition of V kappa-J kappa recombination by the replacement of the Ig kappa intron enhancer suggests that this enhancer is essential for V kappa-J kappa recombination. Images PMID:8508766

14. Inducible nuclear expression of newly synthesized I kappa B alpha negatively regulates DNA-binding and transcriptional activities of NF-kappa B.

PubMed Central

Arenzana-Seisdedos, F; Thompson, J; Rodriguez, M S; Bachelerie, F; Thomas, D; Hay, R T

1995-01-01

The transcription factor NF-kappa B is exploited by many viruses, including the human immunodeficiency virus, for expression of viral genes, but its primary role appears to be in the rapid induction of cellular genes during immune and inflammatory responses. The inhibitor protein I kappa B alpha maintains NF-kappa B in an inactive form in the cytoplasms of unstimulated cells, but upon cell activation, I kappa B alpha is rapidly degraded, leading to nuclear translocation of free NF-kappa B. However, NF-kappa B-dependent transcription of the I kappa B alpha gene leads to rapid resynthesis of the I kappa B alpha protein and inhibition of NF-kappa B-dependent transcription. Here we demonstrate a new regulatory function of I kappa B alpha exerted on NF-kappa B in the nuclear compartment. Although normally found in the cytoplasm, I kappa B alpha, newly synthesized in response to tumor necrosis factor or interleukin I, is transported to the nucleus. In the nucleus I kappa B alpha associates with the p50 and p65 subunits of NF-kappa B, inhibiting DNA binding of the transcription factor. Furthermore, nuclear expression of I kappa B alpha correlates with transcription termination of transfected NF-kappa B-dependent luciferase genes. Following the appearance of I kappa B alpha in the nuclei of activated cells, a dramatic reduction in the amount of nuclear p50 occurs, suggesting that NF-kappa B-I kappa B alpha complexes are cleared from the nucleus. PMID:7739549

15. 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.

16. Kappa distribution in the presence of a potential energy

2015-02-01

The present paper develops the theory and formulations of the kappa distributions that describe particle systems characterized by a nonzero potential energy. As yet, kappa distributions were used for the statistical description of the velocity or kinetic energy of particles but not of the potential energy. With the results provided here, it is straightforward to use the developed kappa distributions to describe any particle population of space plasmas subject to a nonnegligible potential energy. Starting from the kappa distribution of the Hamiltonian function, we develop the distributions that describe either the complete phase space or the marginal spaces of positions and velocities. The study shows, among others: (a) The kappa distributions of velocities that describe space plasmas can be vastly different from the standard formulation of the kappa distribution, because of the presence of a potential energy; the correct formulation should be given by the marginal kappa distribution of velocities by integrating the distribution of the Hamiltonian over the potential energy. (b) The long-standing problem of the divergence of the Boltzmannian exponential distribution for bounded radial potentials is solved using kappa distributions of negative kappa index. (c) Anisotropic distributions of velocities can exist in the presence of a velocity-dependent potential. (d) A variety of applications, including derivations/verifications of the following: (i) the Jeans', the most frequent, and the maximum radii in spherical/linear gravitational potentials; (ii) the Virial theorem for power law potentials; (iii) the generalized barometric formula, (iv) the plasma density profiles in Saturnian magnetosphere, and (v) the average electron magnetic moment in Earth's magnetotail.

17. 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

18. Monoclonal immunoglobulin G1-kappa fibrillary glomerulonephritis.

PubMed

Grove, P; Neale, P H; Peck, M; Schiller, B; Haas, M

1998-01-01

We report here a case of fibrillary glomerulonephritis arising in a 43-year-old man with a polyclonal gammopathy, who presented with progressive renal insufficiency, microscopic hematuria, and mild proteinuria (0.7 g/d). Ultrastructural studies showed deposits of randomly oriented fibrils in the glomerular mesangium and adjacent portions of some glomerular basement membranes, with a mean fibril thickness of 14.3 nm, highly consistent with fibrillary glomerulonephritis. The Congo red stain was negative on histologic sections. Immunofluorescence studies revealed strong mesangial and focal glomerular capillary staining for immunoglobulin (Ig) G, complement (C) 3, and kappa light chains, with minimal staining for IgA, IgM, C1q, or lambda light chains. The IgG present was entirely of the IgG1 subclass. This case is quite unusual for fibrillary glomerulonephritis, which typically presents with polyclonal IgG deposits and IgG4 as the dominant IgG subclass present. Monoclonal deposits are more frequently associated with immunotactoid glomerulopathy, characterized ultrastructurally by microtubule-like structures 30 to 50 nmn thick, often in parallel arrays. The present case illustrates that although fibrillary glomerulonephritis and immunotactoid glomerulopathy might be distinguishable on ultrastructural grounds, there is overlap between these two entities with respect to the potential composition of the glomerular deposits present. PMID:9556416

19. Semisynthetic Neoclerodanes as Kappa Opioid Receptor Probes

PubMed Central

Lovell, Kimberly M.; Vasiljevik, Tamara; Araya, Juan J.; Lozama, Anthony; Prevatt-Smith, Katherine M.; Day, Victor W.; Dersch, Christina M.; Rothman, Richard B.; Butelman, Eduardo R.; Kreek, Mary Jeanne; Prisinzano, Thomas E.

2012-01-01

Modification of the furan ring of salvinorin A (1), the main active component of Salvia divinorum, has resulted in novel neoclerodane diterpenes with opioid receptor affinity and activity. Conversion of the furan ring to an aldehyde at the C-12 position (5) has allowed for the synthesis of analogues with new carbon-carbon bonds at that position. Previous methods for forming these bonds, such as Grignard and Stille conditions, have met with limited success. We report a palladium catalyzed Liebeskind-Srogl cross-coupling reaction of a thioester and a boronic acid that occurs at neutral pH and ambient temperature to produce ketone analogs at C-12. To the best of our knowledge, this is the first reported usage of the Liebeskind-Srogl reaction to diversify a natural product scaffold. We also describe a one-step protocol for the conversion of 1 to 12-epi-1 (3) through microwave irradiation. Previously, this synthetically challenging process has required multiple steps. Additionally, we report in this study that alkene 9 and aromatic analogues 12, 19, 23, 25, and 26 were discovered to retain affinity and selectivity at kappa opioid receptors (KOP). Finally, we report that the furan-2-yl analog of 1 (31) has similar affinity to 1. Collectively, these findings suggest that different aromatic groups appended directly to the decalin core may be well tolerated by KOP receptors, and may generate further ligands with affinity and activity at KOP receptors. PMID:22464684

20. 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.

1. Induction of the nuclear I{kappa}B protein I{kappa}B-{zeta} upon stimulation of B cell antigen receptor

SciTech Connect

Hijioka, Kuniaki; Matsuo, Susumu; Eto-Kimura, Akiko; Takeshige, Koichiro; Muta, Tatsushi . E-mail: tmuta@biology.tohoku.ac.jp

2007-05-04

The nuclear I{kappa}B protein I{kappa}B-{zeta} is barely detectable in resting cells and is induced in macrophages and fibroblasts following stimulation of innate immunity via Toll-like receptors. The induced I{kappa}B-{zeta} associates with nuclear factor (NF)-{kappa}B in the nucleus and plays crucial roles in its transcriptional regulation. Here, we examined the induction of I{kappa}B-{zeta} in B lymphocytes, one of the major players in adaptive immunity. Upon crosslinking of the surface immunoglobulin complex, I{kappa}B-{zeta} mRNA was robustly induced in murine B-lymphoma cell line A20 cells. While the crosslinking activated NF-{kappa}B and induced its target gene, I{kappa}B-{alpha}, co-crosslinking of Fc{gamma} receptor IIB to the surface immunoglobulin complex inhibited NF-{kappa}B activation and the induction of I{kappa}B-{zeta} and I{kappa}B-{alpha}, suggesting critical roles for NF-{kappa}B in the induction. These results indicate that I{kappa}B-{zeta} is also induced by stimulation of B cell antigen receptor, suggesting that I{kappa}B-{zeta} is involved in the regulation of adaptive immune responses.

2. Cytokine-inducible expression in endothelial cells of an I kappa B alpha-like gene is regulated by NF kappa B.

PubMed Central

de Martin, R; Vanhove, B; Cheng, Q; Hofer, E; Csizmadia, V; Winkler, H; Bach, F H

1993-01-01

The transient expression of many different genes is mediated by the inducible transcription factor p50-p65 NF kappa B, which in turn is regulated by complex formation with its inhibitor I kappa B alpha. We describe here that in porcine aortic endothelial cells, either IL-1 alpha, TNF alpha or LPS upregulates an inhibitor of NF kappa B which we refer to as ECI-6. ECI-6 is by structural and functional criteria an I kappa B alpha protein, the porcine homologue of MAD-3, pp40 and RL/IF-1. We have studied the promoter of the ECI-6/I kappa B alpha gene and provide three lines of evidence that its expression is directly regulated by NF kappa B. First, the 5' regulatory region of ECI-6/I kappa B alpha contains two sites that bind NF kappa B in electrophoretic mobility shift assays. Second, expression following transfection of an ECI-6/I kappa B alpha promoter-luciferase reporter construct is dependent on a co-transfected NF kappa B-p65 subunit. Third, pretreatment of endothelial cells with antioxidants, agents that inhibit activation of NF kappa B, inhibit the expression of ECI-6/I kappa B alpha. We conclude that the regulated expression of ECI-6/I kappa B alpha could represent a novel feedback mechanism by which NF kappa B downregulates its own activity after transient activation of target genes has been achieved. Images PMID:8334993

3. Kappa and regional attenuation for Vrancea (Romania) earthquakes

2015-07-01

In this short paper, we investigate ground motion recordings from nine intermediate-depth Vrancea (Romania) earthquakes with M w ≥ 5.2 which occurred between 1986 and 2013. From these recordings, the high-frequency spectral decay parameter (kappa) is computed for 57 seismic stations in Romania. The relation between kappa and several parameters (event, source-to-site distance, soil class, geographical region) is evaluated through inversion techniques. The results show a very distinct influence of the earthquake magnitude and of the geographical position on the kappa values. Subsequently, a conventional frequency-dependent Q model of the form Q( f) = 100* f 1.20 is derived from the geometric spreading functions. The proposed Q model and the site specific kappa values represent the basis for future stochastic simulations of ground motions generated by the Vrancea subcrustal seismic source.

4. 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

5. 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.

6. Obliquely Propagating Electromagnetic Waves in Magnetized Kappa Plasmas

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

7. Purification and mass spectrometric analysis of the kappa opioid receptor.

PubMed

Wannemacher, Kenneth M; Terskiy, Alexandra; Bian, Shengjie; Yadav, Prem N; Li, Hong; Howells, Richard D

2008-09-16

A clonal human embryonic kidney (HEK) 293 cell line was established that stably expressed the rat kappa-opioid receptor (rKOR) with a FLAG epitope at the amino terminus. The Kd for [3H]diprenorphine was 1.1+/-0.2 nM, and the Bmax was 2.6+/-0.4 pmol/mg. Dynorphin A (1-13), U69,593 and naloxone competitively inhibited [3H]diprenorphine binding with Ki values of 2.0, 18 and 18 nM, respectively, in good agreement with previously reported affinities for the unmodified receptor. U69,593 stimulated [35S]GTPgammaS binding in a concentration-dependent manner and caused phosphorylation of mitogen-activated protein (MAP) kinase, indicating that the activated epitope-tagged receptor triggered appropriate signaling pathways. Immunoblot analysis demonstrated that two immunoreactive receptor species with apparent molecular masses of 42 and 52 kDa were expressed. Previous studies indicated that the 42 kDa protein was localized intracellularly and was a precursor of the 52 kDa receptor, which was present at the cell surface. rKOR was extracted from transfected HEK 293 cell membranes with n-dodecyl-beta-D-maltopyranoside. Sequential use of wheat germ agglutinin chromatography, Sephacryl S300 gel filtration chromatography, anti-FLAG immunoaffinity chromatography and SDS/PAGE permitted purification of the 52 kDa receptor. MALDI-TOF mass spectrometry was used to identify peptides derived from rKOR following sequential in-gel digestion with trypsin and cyanogen bromide. Eighteen rKOR peptides were detected, corresponding to 27.1% coverage of the receptor. Precursor-selective MS/MS confirmed the identity of most of these peptides. In addition, we have identified heat shock protein 70 (HSP70) as a rKOR-interacting protein. PMID:18656460

8. 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

9. Sex Differences in Kappa Opioid Pharmacology

PubMed Central

Rasakham, Khampaseuth; Liu-Chen, Lee-Yuan

2012-01-01

In recent years it has become apparent that sex is a major factor involved in modulating the pharmacological effects of exogenous opioids. The kappa opioid receptor (KOPR) system is a potential therapeutic target for pain, mood disorders and addiction. In humans mixed KOPR/MOPR ligands have been found to produce greater analgesia in women than men. In contrast, in animals, selective KOPR agonists have been found to produce greater antinociceptive effects in males than females. Collectively, the studies indicate that the direction and magnitude of sex differences of KOPR-mediated antinociception/analgesia are dependent on species, strain, ligand and pain model examined. Of interest, and less studied, is whether sex differences in other KOPR-mediated effects exist. In the studies conducted thus far, greater effects of KOPR agonists in males have been found in neuroprotection against stroke and suppression of food intake behavior. On the other hand, greater effects of KOPR agonists were found in females in mediation of prolactin release. In modulation of drugs of abuse, sex differences in KOPR effects were observed but appear to be dependent on the drug examined. The mechanism(s) underlying sex differences in KOPR-mediated effects may be mediated by sex chromosomes, gonadal hormonal influence on organization (circuitry) and/or acute hormonal influence on KOPR expression, distribution and localization. In light of the diverse pharmacology of KOPR we discuss the need for future studies characterizing the sexual dimorphism of KOPR neural circuitry and in examining other behaviors and processes that are modulated by the KOPR. PMID:20951148

10. 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.

11. 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.

12. Inhibition of NF-kappa B activation by peptides targeting NF-kappa B essential modulator (nemo) oligomerization.

PubMed

Agou, Fabrice; Courtois, Gilles; Chiaravalli, Jeanne; Baleux, Françoise; Coïc, Yves-Marie; Traincard, François; Israël, Alain; Véron, Michel

2004-12-24

NF-kappa B essential modulator/IKK-gamma (NEMO/IKK-gamma) plays a key role in the activation of the NF-kappa B pathway in response to proinflammatory stimuli. Previous studies suggested that the signal-dependent activation of the IKK complex involves the trimerization of NEMO. The minimal oligomerization domain of this protein consists of two coiled-coil subdomains named Coiled-coil 2 (CC2) and leucine zipper (LZ) (Agou, F., Traincard, F., Vinolo, E., Courtois, G., Yamaoka, S., Israel, A., and Veron, M. (2004) J. Biol. Chem. 279, 27861-27869). To search for drugs inhibiting NF-kappa B activation, we have rationally designed cell-permeable peptides corresponding to the CC2 and LZ subdomains that mimic the contact areas between NEMO subunits. The peptides were tagged with the Antennapedia/Penetratin motif and delivered to cells prior to stimulation with lipopolysaccharide. Peptide transduction was monitored by fluorescence-activated cell sorter, and their effect on lipopolysaccharide-induced NF-kappa B activation was quantified using an NF-kappa B-dependent beta-galactosidase assay in stably transfected pre-B 70Z/3 lymphocytes. We show that the peptides corresponding to the LZ and CC2 subdomains inhibit NF-kappa B activation with an IC(50) in the mum range. Control peptides, including mutated CC2 and LZ peptides and a heterologous coiled-coil peptide, had no inhibitory effect. The designed peptides are able to induce cell death in human retinoblastoma Y79 cells exhibiting constitutive NF-kappa B activity. Our results provide the "proof of concept" for a new and promising strategy for the inhibition of NF-kappa B pathway activation through targeting the oligomerization state of the NEMO protein. PMID:15466857

13. Sahlgrenska Excess Skin Questionnaire (SESQ): a reliable questionnaire to assess the experience of excessive skin after weight loss.

PubMed

Biörserud, Christina; Nielsen, Christina; Staalesen, Trude; Elander, Anna; Olbers, Torsten; Olsén, Monika Fagevik

2013-02-01

There is a lack of knowledge and reliable measurement instruments to assess excess skin after massive weight loss. The purpose of this study was to test the reliability of a new self-administered questionnaire. A self-administered questionnaire, the Sahlgrenska Excess Skin Questionnaire (SESQ) was designed to assess excess skin after weight loss. The questionnaire includes 30 questions about demographic data, activity and daily life and excess skin on specific body parts and the body as a whole. Forward and backward translations were made by two independent professional translators, from Swedish to English and then back to Swedish. The questionnaire was tested on 10 patients from Sweden and England and was followed by an interview with each patient. Minor corrections were made. A test-retest was carried out to evaluate the reliability by sending the Swedish questionnaire to 46 subjects with weight loss after obesity surgery, dieting, or medication. The test-retest reliability of questions concerning activity and daily life between the two occasions had a Percentage Of Agreement (POA) of 49%-76% and a weighted Kappa of 0.44-0.78. The questions about the degree of excess skin on specific body parts had a POA of 50%-76% and a weighted Kappa of 0.53-0.81. Excess skin perceived as causing problems had a POA of 32%-57 %, an adjusted POA of 63%-87%, and an Intra-Class Correlation of 0.72-0.92. The SESQ is reliable for evaluating patients' experience of excess skin after massive weight loss. PMID:23190023

14. Weight Estimation Tool for Children Aged 6 to 59 Months in Limited-Resource Settings

PubMed Central

2016-01-01

Importance A simple, reliable anthropometric tool for rapid estimation of weight in children would be useful in limited-resource settings where current weight estimation tools are not uniformly reliable, nearly all global under-five mortality occurs, severe acute malnutrition is a significant contributor in approximately one-third of under-five mortality, and a weight scale may not be immediately available in emergencies to first-response providers. Objective To determine the accuracy and precision of mid-upper arm circumference (MUAC) and height as weight estimation tools in children under five years of age in low-to-middle income countries. Design This was a retrospective observational study. Data were collected in 560 nutritional surveys during 1992–2006 using a modified Expanded Program of Immunization two-stage cluster sample design. Setting Locations with high prevalence of acute and chronic malnutrition. Participants A total of 453,990 children met inclusion criteria (age 6–59 months; weight ≤ 25 kg; MUAC 80–200 mm) and exclusion criteria (bilateral pitting edema; biologically implausible weight-for-height z-score (WHZ), weight-for-age z-score (WAZ), and height-for-age z-score (HAZ) values). Exposures Weight was estimated using Broselow Tape, Hong Kong formula, and database MUAC alone, height alone, and height and MUAC combined. Main Outcomes and Measures Mean percentage difference between true and estimated weight, proportion of estimates accurate to within ± 25% and ± 10% of true weight, weighted Kappa statistic, and Bland-Altman bias were reported as measures of tool accuracy. Standard deviation of mean percentage difference and Bland-Altman 95% limits of agreement were reported as measures of tool precision. Results Database height was a more accurate and precise predictor of weight compared to Broselow Tape 2007 [B], Broselow Tape 2011 [A], and MUAC. Mean percentage difference between true and estimated weight was +0.49% (SD = 10

15. Obliquely propagating electromagnetic waves in magnetized kappa plasmas

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.

16. Three NF-kappa B sites in the I kappa B-alpha promoter are required for induction of gene expression by TNF alpha.

PubMed Central

Ito, C Y; Kazantsev, A G; Baldwin, A S

1994-01-01

NF-kappa B was first identified as a postive regulator which bound to a 10 bp sequence in the first intron of the Ig kappa light chain gene. Further characterization of this transcription factor has revealed that NF-kappa B is kept from binding to its consensus sequence by its inhibitor, IkB-alpha, which retains NF-kappa B in the cytoplasm. Upon receiving various extra- and intracellular signals, I kappa B-alpha is rapidly degraded and NF-kappa B is induced to translocate into the nucleus. This process precedes the rapid induction of I kappa B-alpha mRNA and protein. To understand how I kappa B-alpha is replenished, we have cloned and sequenced the 5' flanking region of the I kappa B-alpha gene and have identified the transcription start site and three NF-kappa B sites in this region. Further characterization of these NF-kappa B sites show that they have different affinities for three specific protein complexes which we identify here to consist of various members of the Rel family. In transient assays, cotransfection with a p65 expression vector is able to activate an I kappa B-alpha promoter-CAT reporter construct and all three NF-kappa B sites are required for full activation of the I kappa B-alpha gene following stimulation with TNF-alpha. Our data confirm a transcriptional autoregulatory loop involved in maintaining appropriate NF-kappa B and I kappa B-alpha levels in the cell. Images PMID:7937093

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

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.

18. 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

19. 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

20. Quasi-thermal noise in space plasma: 'kappa' distributions

SciTech Connect

Le Chat, G.; Issautier, K.; Meyer-Vernet, N.; Maksimovic, M.; Moncuquet, M.; Zouganelis, I.

2009-10-15

The transport of energy in collisionless plasmas, especially in space plasmas, is far from being understood. Measuring the temperature of the electrons and their nonthermal properties can give important clues to understand the transport properties. Quasi-thermal noise (QTN) spectroscopy is a reliable tool for measuring accurately the electron density and temperature since it is less sensitive to the spacecraft perturbations than particle detectors. This work models the plasma QTN using a generalized Lorentzian ('kappa') distribution function for the electrons. This noise is produced by the quasi-thermal fluctuations of the electrons and by the Doppler-shifted thermal fluctuations of the ions. A sum of two Maxwellian functions has mainly been used for modeling the QTN of the electrons, but the observations have shown that the electrons are better fitted by a kappa distribution function. Pioneer work on QTN calculation only considered integer values of {kappa}. This paper extends these calculations to real values of {kappa} and gives the analytic expressions and numerical calculations of the QTN with a kappa distribution function. This paper shows some generic properties and gives some practical consequences for plasma wave measurements in space.

1. 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

2. 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.

3. 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

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

SciTech Connect

Lee, Kyoung-Hee; Lee, Choon-Taek; Kim, Young Whan ||; Han, Sung Koo ||; Shim, Young-Soo ||; Yoo, Chul-Gyu ||. E-mail: cgyoo@snu.ac.kr

2005-07-01

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

5. Interfacial phenomena in high-kappa dielectrics

Mathew, Anoop

The introduction of novel high-kappa dielectric materials to replace the traditional SiO2 insulating layer in CMOS transistors is a watershed event in the history of transistor development. Further, replacement of the traditional highly-doped polycrystalline silicon gate electrode with a new set of materials for metal gates complicates the transition and introduces further integration challenges. A whole variety of new material surfaces and interfaces are thus introduced that merit close investigation to determine parameters for optimal device performance. Nitrogen is a key component that improves the performance of a variety of materials for the next generation of these CMOS transistors. Nitrogen is introduced into new gate dielectric materials such as hafnium silicates as well as in potential metal gate materials such as hafnium nitride. A photoemission study of the binding energies of the various atoms in these systems using photoemission reveals the nature of the atomic bonding. The current study compares hafnium silicates of various compositions which were thermally nitrided at different temperatures in ammonia, hafnium nitrides, and thin HfO2 films using photoelectron spectroscopy. A recurring theme that is explored is the competition between oxygen and nitrogen atoms in bonding with hafnium and other atoms. The N 1s photoemission peak is seen to have contributions from its bonding with hafnium, oxygen, and silicon atoms. The Hf 4f and O 1s spectra similarly exhibit signatures of their bonding environment with their neighboring atoms. Angle resolved photoemission and in-situ annealing/argon sputtering experiments are used to elucidate the nature of the bonding and its evolution with processing. A nondestructive profilitng of nitrogen distribution as a function of composition in nitrided hafnium silicates is also constructed using angle resolved photoemission as a function of the take-off angle. These results are corroborated with depth reconstruction obtained

6. Weighted aggregation

NASA Technical Reports Server (NTRS)

Feiveson, A. H. (Principal Investigator)

1979-01-01

The use of a weighted aggregation technique to improve the precision of the overall LACIE estimate is considered. The manner in which a weighted aggregation technique is implemented given a set of weights is described. The problem of variance estimation is discussed and the question of how to obtain the weights in an operational environment is addressed.

7. 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}.

8. Kappa Snyder deformations of Minkowski spacetime, realizations, and Hopf algebra

SciTech Connect

Meljanac, S.; Meljanac, D.; Samsarov, A.; Stojic, M.

2011-03-15

We present Lie-algebraic deformations of Minkowski space with undeformed Poincare algebra. These deformations interpolate between Snyder and {kappa}-Minkowski space. We find realizations of noncommutative coordinates in terms of commutative coordinates and derivatives. By introducing modules, it is shown that, although deformed and undeformed structures are not isomorphic at the level of vector spaces, they are isomorphic at the level of Hopf-algebraic action on corresponding modules. Invariants and tensors with respect to Lorentz algebra are discussed. A general mapping from {kappa}-deformed Snyder to Snyder space is constructed. The deformed Leibniz rule, the Hopf structure, and the star product are found. Special cases, particularly Snyder and {kappa}-Minkowski in Maggiore-type realizations, are discussed. The same generalized Hopf-algebraic structures are considered as well in the case of an arbitrary allowable kind of realization, and results are given perturbatively up to second order in deformation parameters.

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

SciTech Connect

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.

10. 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.

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

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.

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

DOEpatents

Chai, Xin-Sheng; Zhu, Jun Yong

2002-01-01

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

13. A Simulation Study of Rater Agreement Measures with 2x2 Contingency Tables

ERIC Educational Resources Information Center

Ato, Manuel; Lopez, Juan Jose; Benavente, Ana

2011-01-01

A comparison between six rater agreement measures obtained using three different approaches was achieved by means of a simulation study. Rater coefficients suggested by Bennet's [sigma] (1954), Scott's [pi] (1955), Cohen's [kappa] (1960) and Gwet's [gamma] (2008) were selected to represent the classical, descriptive approach, [alpha] agreement…

14. Lack of feedback inhibition of V kappa gene rearrangement by productively rearranged alleles.

PubMed

1991-02-01

Circular DNAs excised by immunoglobulin kappa chain gene rearrangements were cloned and characterized. 16 of 17 clones examined were double recombination products containing a V kappa-J kappa rearrangement (coding joint) as well as the reciprocal element (signal joint) of another V kappa-J kappa rearrangement. These products suggested multiple recombination, primary inversion, and secondary excision. In primary events, 5 of 16 translational reading frames were in-phase. Thus, V kappa gene rearrangement may not be inhibited by the presence of a productively rearranged allele. An unusually large trinucleotide (P) insertion forming a palindrome of 12 nucleotides was also observed in one of the coding joints. PMID:1988542

15. 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.

16. B lineage-restricted rearrangement of a human Ig kappa transgene.

PubMed

Cavelier, P; Nato, F; Coquilleau, I; Rolink, A; Rougeon, F; Goodhardt, M

1997-07-01

To study the control of immunoglobulin kappa light chain gene rearrangement, we generated transgenic mice carrying a germ-line human kappa minilocus (HK) containing the J kappa-proximal V gene, V kappa IV, the V-J intergenic region, the five J kappa segments and the C kappa gene. This construct includes the intronic, but not the 3' kappa enhancer. Rearrangement of the HK transgene was found to be lymphoid specific and restricted to the B cell lineage. Quantification of kappa gene rearrangement in pre-B cell lines established from HK transgenic mice showed that, like endogenous kappa genes, rearrangement of the transgene is repressed in mu-negative early B cell precursors. These results indicate that rearrangement of the HK transgene is subjected to the same B/T cell and developmental regulation as V kappa-J kappa rearrangement at the endogenous locus. Comparison with an unrearranged kappa transgenic construct lacking the V-J intergenic region, suggests that this region, or elements associated with the proximal V gene, may act to restrict kappa gene rearrangement to the B cell lineage. PMID:9247570

17. Mining agreements III

SciTech Connect

Not Available

1991-01-01

This book cover the following: Forms of mining agreements; Preliminary letter agreements; Acquisition of mineral interests involving securities; Partnership tax treatment in mining agreements; Non-tax consequences of partnerships under state law; Protection against joint venturers' liabilities; Joint venture decision making; Mining royalties; Commingling and unitization provisions; Indemnification and insurance provisions; Area of interest provision; Dispute resolution; and Non-participation and default provisions.

18. Misinterpretations in agreement and agreement attraction.

PubMed

Patson, Nikole D; Husband, E Matthew

2016-05-01

It has been well established that subject-verb number agreement can be disrupted by local noun phrases that differ in number from the subject head noun phrase. In sentence production, mismatches in the grammatical number of the head and local noun phrases lead to agreement errors on the verb as in: the key to the cabinets are. Similarly, although ungrammaticality typically causes disruption in measures of sentence comprehension, the disruption is reduced when the local noun phrase has a plural feature. Using a forced-choice comprehension question method, we report two experiments that provide evidence that comprehenders were likely to misinterpret the number information on the head noun phrase when morphosyntactic number markings on the local noun phrase and verb did not match the head. These results are consistent with a growing body of research that suggests that comprehenders often arrive at a final interpretation of a sentence that is not faithful to the linguistic input. PMID:25624171

19. Body Weight

MedlinePlus

... heart failure, and kidney disease. Good nutrition and exercise can help in losing weight. Eating extra calories within a well-balanced diet and treating any underlying medical problems can help to add weight.

20. Weight Control

MedlinePlus

... obese. Achieving a healthy weight can help you control your cholesterol, blood pressure and blood sugar. It ... use more calories than you eat. A weight-control strategy might include Choosing low-fat, low-calorie ...

1. Body Weight

MedlinePlus

... to medicines, thyroid problems, heart failure, and kidney disease. Good nutrition and exercise can help in losing weight. Eating extra calories within a well-balanced diet and treating any underlying medical problems can help to add weight.

2. 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.

3. Alpha Kappa Alpha Sorority's Reading Improvement Program for Minorities.

ERIC Educational Resources Information Center

This document discusses the founding and establishment of Alpha Kappa Alpha Sorority's reading experience pilot project. The efforts of this project were aligned with those of Right to Read and Reading Is Fundamental (RIF). Because of the response from parents and children, plans are being made to increase present operations within the next…

4. 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.

5. Kappa statistic for the clustered dichotomous responses from physicians and patients

PubMed Central

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

2013-01-01

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 to the asymptotic standard error estimate that ignores dependence among patients within physicians with at least a moderately large number of clusters. An example of an application to a coronary heart disease prevention study is presented. PMID:23533082

6. 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)

7. 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…

8. [Polymorphism of the kappa-casein gene in populations of the subfamily Bovinae].

PubMed

Sulimova, G E; Badagueva, Iu N; Udina, I G

1996-11-01

Polymorphism of the 5'-untranslated region and exon 4 of kappa-casein (kappa-casein) gene was studied in Yakutian and Black Pied cattle, yak, European bison, and buffalo by means of a polymerase chain reaction and subsequent restriction fragment length polymorphism analysis (PCR-RFLP). In the species studied, restriction polymorphism by the endonucleases AluI and Bg/II in the 5'-untranslated region of the gene is absent. Four restriction endonucleases testing nucleotide substitutions in 136 codon (TaqI), 148 codon (HinfI and HindIII), and 167 and 168 codons (PstI) were used to study polymorphism of exon 4. The use of several restriction endonucleases allowed three alleles of kappa-casein (kappa-CnA, kappa-CnB, kappa-CnF) to be typed and new allele variants in yak, European bison, and buffalo to be revealed. Nucleotide sequences of the fragments of exon 4 studied were determined for two new alleles of the gene: kappa-CnG in yak and European bison and kappa-CnH in buffalo. Nucleotide substitutions determining new alleles were localized. In kappa-CnG, 148 and 168 codons coincide with the corresponding codons of kappa-CnB, and 136 and 167 codons correspond to kappa-CnA. Stop codons of kappa-CnG in yak are different from stop codons of other alleles of the gene: TGA, instead of TAA. The nucleotide sequence of exon 4 of kappa-CnH differs from bovine kappa-CnA by 15 nucleotide substitutions, causing 10 amino acid changes in the protein sequence, which coincide with the corresponding known amino acid sequence of kappa-casein in buffalo. Interbreed and interspecies differences in the profile of allele frequencies of the species studied were revealed. Aspects connected with evolution of the alleles of kappa-casein are discussed. PMID:9119217

9. 7 CFR 981.9 - Kernel weight.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 8 2011-01-01 2011-01-01 false Kernel weight. 981.9 Section 981.9 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Regulating Handling Definitions § 981.9 Kernel weight. Kernel weight means the weight of kernels,...

10. 7 CFR 981.9 - Kernel weight.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Kernel weight. 981.9 Section 981.9 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Regulating Handling Definitions § 981.9 Kernel weight. Kernel weight means the weight of kernels,...

11. Effect of Daisaikoto on Expressions of SIRT1 and NF-kappaB of Diabetic Fatty Liver Rats Induced by High-Fat Diet and Streptozotocin

PubMed Central

Qian, Weibin; Cai, Xinrui; Zhang, Xinying; Wang, Yingying; Qian, Qiuhai; Hasegawa, Junichi

2016-01-01

Background Daisaikoto (DSKT), a classical traditional Chinese herbal formula, has been used for treating digestive diseases for 1800 years in China. Therefore, in this study, we are going to investigate the effect of DSKT on diabetic fatty liver rats induced by a high-fat diet and streptozotocin (STZ), and the effects of DSKT on silent mating type information regulation 2 homolog 1 (SIRT1) and nuclear factor kappa B (NF-kappaB). Methods Diabetic fatty liver rat model was selected to establish a high-fat diet and STZ. Sixty Wistar rats were divided into six groups (n = 10): control group, high-fat diet + STZ group, simvastatin treatment group, DSKT low dose, medial dose and high dose treatment groups. After 8 weeks of drug intervention, body and liver weights, blood chemistry, blood glucose and insulin were examined. The expressions of sirtuin 1 and NF-kappaB in the liver were observed by RT-PCR and immunohistochemistry, respectively. Results A high-fat diet increased body, liver weights, and serum cholesterol concentrations. Intraperitoneal injection of STZ increased blood glucose and decreased body weights. DSKT improved them. Homeostasis model assessment-estimated insulin resistance (HOMA-IR) indices were increased in the high-fat diet groups. DSKT improved them too. In histological examinations of the liver, we observed a significant improvement after treatment. Immunostaining expression of NF-kappaB in the liver was improved by DSKT and simvastatin. The mRNA expressions of SIRT1 in the liver were increased by DSKT and simvastatin. Conclusion We have demonstrated that DSKT is capable of reversing dyslipidemia and insulin resistance induced by a high-fat diet and STZ. High dose DSKT reveals a stronger effect than simvastatin on the expressions of SIRT1 and NF-kappaB. Furthermore, DSKT has shown a strong dose-depended protective effect on diabetic fatty liver. PMID:27493486

12. CCK independently activates intracellular trypsinogen and NF-kappaB in rat pancreatic acinar cells.

PubMed

Han, B; Ji, B; Logsdon, C D

2001-03-01

In the cholecystokinin (CCK) hyperstimulation model of acute pancreatitis, two early intracellular events, activation of trypsinogen and activation of nuclear factor-kappaB (NF-kappaB), are thought to be important in the development of the disease. In this study, the relationship between these two events was investigated. NF-kappaB activity was monitored by using a DNA binding assay and mob-1 chemokine gene expression. Intracellular trypsin activity was measured by using a fluorogenic substrate. Protease inhibitors including FUT-175, Pefabloc, and E-64d prevented CCK stimulation of intracellular trypsinogen and NF-kappaB activation. Likewise, the NF-kappaB inhibitors pyrrolidine dithiocarbamate and N-acetyl-L-cysteine inhibited CCK stimulation of NF-kappaB and intracellular trypsinogen activation. These results suggested a possible codependency of these two events. However, CCK stimulated NF-kappaB activation in Chinese hamster ovary-CCK(A) cells, which do not express trypsinogen, indicating that trypsin is not necessary for CCK activation of NF-kappaB. Furthermore, adenovirus-mediated expression in acinar cells of active p65 subunits to stimulate NF-kappaB, or of inhibitory kappaB-alpha molecules to inhibit NF-kappaB, did not affect either basal or CCK-mediated trypsinogen activation. Thus trypsinogen and NF-kappaB activation are independent events stimulated by CCK. PMID:11171565

13. The nuclear signaling of NF-kappaB: current knowledge, new insights, and future perspectives.

PubMed

Wan, Fengyi; Lenardo, Michael J

2010-01-01

The nuclear factor-kappa B (NF-kappaB) transcription factor plays a critical role in diverse cellular processes associated with proliferation, cell death, development, as well as innate and adaptive immune responses. NF-kappaB is normally sequestered in the cytoplasm by a family of inhibitory proteins known as inhibitors of NF-kappaB (IkappaBs). The signal pathways leading to the liberation and nuclear accumulation of NF-kappaB, which can be activated by a wide variety of stimuli, have been extensively studied in the past two decades. After gaining access to the nucleus, NF-kappaB must be actively regulated to execute its fundamental function as a transcription factor. Recent studies have highlighted the importance of nuclear signaling in the regulation of NF-kappaB transcriptional activity. A non-Rel subunit of NF-kappaB, ribosomal protein S3 (RPS3), and numerous other nuclear regulators of NF-kappaB, including Akirin, Nurr1, SIRT6, and others, have recently been identified, unveiling novel and exciting layers of regulatory specificity for NF-kappaB in the nucleus. Further insights into the nuclear events that govern NF-kappaB function will deepen our understanding of the elegant control of its transcriptional activity and better inform the potential rational design of therapeutics for NF-kappaB-associated diseases. PMID:19997086

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

ERIC Educational Resources Information Center

Zwick, Rebecca; Lenaburg, Lubella

2009-01-01

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

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

SciTech Connect

Takata, Akemi; Otsuka, Motoyuki; Kojima, Kentaro; Yoshikawa, Takeshi; Kishikawa, Takahiro; Yoshida, Haruhiko; Koike, Kazuhiko

2011-08-12

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

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

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.

17. NPOI Observations of the Exoplanet Host Kappa Coronae Borealis

Baines, Ellyn K.; Armstrong, J. T.; van Belle, G.

2014-01-01

Kappa Coronae Borealis is a "retired A star", otherwise known as a former A-type dwarf that is now a K-type subgiant. It is a particularly fascinating target because of its unusual configuration of companions and dust rings. It hosts at least one exoplanet and perhaps two, and features a single wide dust ring or two narrow ones. We observed the star interferometrically in order to characterize the main star and the environment in which the planet(s) and dust ring(s) reside. We determined a variety of fundamental parameters for kappa CrB: the limb-darkened angular diameter, physical size, effective temperature, luminosity, mass, age, and the extent of the habitable zone range. We combined our mass with the orbital parameters from four sources from the literature to calculate the planet's mass as well.

18. Speed Constancy or Only Slowness: What Drives the Kappa Effect

PubMed Central

Chen, Youguo; Zhang, Bangwu; Kording, Konrad Paul

2016-01-01

In the Kappa effect, two visual stimuli are given, and their spatial distance affects their perceived temporal interval. The classical model assumes constant speed while a competing Bayesian model assumes a slow speed prior. The two models are based on different assumptions about the statistical structure of the environment. Here we introduce a new visual experiment to distinguish between these models. When fit to the data, both the two models replicated human response, but the slowness model makes better behavioral predictions than the speed constancy model, and the estimated constant speed is close to the absolute threshold of speed. Our findings suggest that the Kappa effect appears to be due to slow speeds, and also modulated by spatial variance. PMID:27100097

19. Kappa distribution and Probability Density Functions in Solar Wind

Jurac, S.

2004-12-01

A signature of a statistical intermittency is the presence of large deviations from the average value: this increased probability of finding extreme deviations is characterized by Probability Density Functions (PDFs) which exhibit non Gaussian power-law tails. Such power-law distributions were observed over decades in biology, chemistry, finance and other fields. Known examples include heartbeat histograms, price distribution, turbulent fluid flow and many other non-equilibrium systems. It is shown that the Kappa distribution represents a good description of PDFs observed in Solar wind. The asymmetric fluctuations in variance over time observed in solar wind PDFs are Gamma distributed. It is shown that, by assuming such a distribution of variance, the Kappa distribution can be analitically derived.

20. Radio Emissions from Plasma with Electron Kappa-Distributions

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

1. Estrogen inhibits phorbol ester-induced I kappa B alpha transcription and protein degradation.

PubMed

Sun, W H; Keller, E T; Stebler, B S; Ershler, W B

1998-03-27

Estrogen (E2) is known to prevent bone loss and the mechanism is, at least in part, mediated by inhibition of expression of cytokines such as interleukin-6 (IL-6). Expression of IL-6 is tightly regulated and the transcription factor NF kappa B can upregulate IL-6 gene expression by binding to its promoter region. NF kappa B is kept in an inactive state by associating with its cytoplasmic inhibitor I kappa B alpha. Upon mitogenic stimulation, I kappa B alpha becomes phosphorylated, followed by a rapid protein degradation. As a result, NF kappa B is released and translocate to the nucleus where DNA binding occurs. It has been shown that E2 treatment downregulates mitogen-induced IL-6 expression by inhibiting NF kappa B activity. Here, we sought to determine whether E2 regulates IL-6 gene expression by modulating the levels of I kappa B alpha. Our results show that E2 treatment almost completely inhibits phorbol ester-induced I kappa B alpha protein degradation. In addition, E2 inhibits phorbol ester-stimulated I kappa B alpha gene expression. Taken together, our results suggest that E2 maintains steady state levels of I kappa B alpha upon mitogen stimulation, resulting in inhibition of NF kappa B activation and IL-6 gene expression. This may explain the protective effect of E2 on bone loss. PMID:9535726

2. Weight Management

MedlinePlus

... Quit Smoking Benefits of Quitting Health Effects of Smoking Secondhand Smoke Withdrawal Ways to Quit QuitGuide Pregnancy & Motherhood Pregnancy & Motherhood Before Your Baby is Born From Birth to 2 Years Quitting for Two SmokefreeMom Healthy Kids Parenting & ... Weight Management Weight Management ...

3. Weighted Configuration Model

Serrano, M. Ángeles; Boguñá, Marián

2005-06-01

The configuration model is one of the most successful models for generating uncorrelated random networks. We analyze its behavior when the expected degree sequence follows a power law with exponent smaller than two. In this situation, the resulting network can be viewed as a weighted network with non trivial correlations between strength and degree. Our results are tested against large scale numerical simulations, finding excellent agreement.

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

SciTech Connect

Koh, Dow-Mu Chau, Ian; Tait, Diana; Wotherspoon, Andrew; Cunningham, David; Brown, Gina

2008-06-01

5. 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.

6. Using Relative Improvement over Chance (RIOC) to Examine Agreement between Tests: Three Case Examples Using Studies of Developmental Coordination Disorder (DCD) in Children

ERIC Educational Resources Information Center

Cairney, John; Streiner, David L.

2011-01-01

Although statistics such as kappa and phi are commonly used to assess agreement between tests, in situations where the base rate of a disorder in a population is low or high, these statistics tend to underestimate actual agreement. This can occur even if the tests are good and the classification of subjects is adequate. Relative improvement over…

7. 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.

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

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.

9. Activation of nuclear factor-kappaB in dogs with chronic enteropathies.

PubMed

Luckschander, Nicole; Hall, Jean A; Gaschen, Frédéric; Forster, Ursula; Wenzlow, Nanny; Hermann, Pascal; Allenspach, Karin; Dobbelaere, Dirk; Burgener, Iwan A; Welle, Monika

2010-02-15

Homeostasis in the intestinal microenvironment between the immune system and luminal antigens appears disturbed in chronic enteropathies. Pro-inflammatory cytokines likely play a role in the pathogenesis of intestinal inflammation. Several inflammatory and immunoregulatory genes have associated nuclear factor-kappaB (NF-kappaB) binding sites, which allow NF-kappaB to regulate gene transcription. The purpose of this study was to investigate (1) the occurrence of NF-kappaB activation during mucosal inflammation in situ, (2) the mucosal distribution pattern of cells expressing activated NF-kappaB within treatment groups, and (3) the effect of specific therapy on NF-kappaB activation. Dogs with chronic enteropathy were studied (n=26) and compared with 13 healthy dogs. Ten dogs had food responsive disease (FRD) and 16 had inflammatory bowel disease (IBD). NF-kappaB activation was detected in duodenal mucosal biopsies using a mouse monoclonal antibody (MAB 3026) that selectively binds the nuclear localization sequence of activated NF-kappaB. To identify macrophages, biopsies were stained using the MAC 387 antibody. Macrophages in the lamina propria double-stained for MAC 387 and NF-kappaB were quantitated; epithelial cell expression of activated NF-kappaB was determined semi-quantitatively. Results showed that more macrophages positive for activated NF-kappaB were present in lamina propria of dogs with chronic enteropathy compared to control dogs (p<0.01). More NF-kappaB positive epithelial cells were observed in FRD dogs compared to IBD dogs (p<0.05). After therapy, the number of macrophages and epithelial cells staining positive for activated NF-kappaB decreased (p<0.01) in chronic enteropathy dogs. In conclusion, activation of NF-kappaB is closely associated with the pathophysiology of canine chronic enteropathy. Down-regulation follows successful therapy. PMID:19740552

SciTech Connect

Wetmiller, R.J.; Lyons, J.A.; Shannon, W.E.; Munro, P.S.; Thomas, J.T.; Andrew, M.D.; Lamontagne, M.; Wong, C., Anglin, F.M.; Plouffe, M.; Lapointe, S.P.; Adams, J.; Drysdale, J.A. . Geophysics Div.)

1990-04-01

This is the twenty-first progress report under the agreement entitled Canadian Seismic Agreement between the US Nuclear Regulatory Commission (NRC) and the Canadian Commercial Corporation. Activities undertaken by the Geophysics Division of the Geological Survey of Canada (GD/GSC) during the period from July 01, 1988 to June 30, 1989 and supported in part by the NRC agreement are described below under four headings; Eastern Canada Telemetred Network and local network developments, Datalab developments, strong motion network developments and earthquake activity. In this time period eastern Canada experienced its largest earthquake in over 50 years. This earthquake, which has been christened the Saguenay earthquake, has provided a wealth of new data pertinent to earthquake engineering studies in eastern North America and is the subject of many continuing studies, which are presently being carried out at GD and elsewhere. 41 refs., 21 figs., 7 tabs.

11. 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.

SciTech Connect

Wetmiller, R.J.; Lyons, J.A.; Shannon, W.E.; Munro, P.S.; Thomas, J.T.; Andrew, M.D.; Lapointe, S.P.; Lamontagne, M.; Wong, C.; Anglin, F.M.; Adams, J.; Cajka, M.G.; McNeil, W.; Drysdale, J.A. )

1992-05-01

This is a progress report of work carried out under the terms of a research agreement entitled the Canadian Seismic Agreement'' between the US Nuclear Regulatory Commission (USNRC), the Canadian Commercial Corporation and the Geophysics Division of the Geological Survey of Canada (GD/GSC) during the period from July 01, 1989 to June 30, 1990. The Canadian Seismic Agreement'' supports generally the operation of various seismograph stations in eastern Canada and the collection and analysis of earthquake data for the purpose of mitigating seismic hazards in eastern Canada and the northeastern US. The specific activities carried out in this one-year period are summarized below under four headings; Eastern Canada Telemetred Network and local network developments, Datalab developments, strong-motion network developments and earthquake activity. During this period the first surface fault unequivocably determined to have accompanied a historic earthquake in eastern North America, occurred in northern Quebec.

13. 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

14. Weight simulator

NASA Technical Reports Server (NTRS)

Howard, W. H.; Young, D. R.

1972-01-01

Device applies compressive force to bone to minimize loss of bone calcium during weightlessness or bedrest. Force is applied through weights, or hydraulic, pneumatic or electrically actuated devices. Device is lightweight and easy to maintain and operate.

15. Stevioside ameliorates high-fat diet-induced insulin resistance and adipose tissue inflammation by downregulating the NF-{kappa}B pathway

SciTech Connect

Wang, Zhiquan; Xue, Liqiong; Guo, Cuicui; Han, Bing; Pan, Chunming; Zhao, Shuangxia; Song, Huaidong; Ma, Qinyun

2012-01-27

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

PubMed

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

2015-01-01

High-resolution esophageal manometry (HRM) is a recent development used in the evaluation of esophageal function. Our aim was to assess the inter-observer agreement for diagnosis of esophageal motility disorders using this technology. Practitioners registered on the HRM Working Group website were invited to review and classify (i) 147 individual water swallows and (ii) 40 diagnostic studies comprising 10 swallows using a drop-down menu that followed the Chicago Classification system. Data were presented using a standardized format with pressure contours without a summary of HRM metrics. The sequence of swallows was fixed for each user but randomized between users to avoid sequence bias. Participants were blinded to other entries. (i) Individual swallows were assessed by 18 practitioners (13 institutions). Consensus agreement (≤ 2/18 dissenters) was present for most cases of normal peristalsis and achalasia but not for cases of peristaltic dysmotility. (ii) Diagnostic studies were assessed by 36 practitioners (28 institutions). Overall inter-observer agreement was 'moderate' (kappa 0.51) being 'substantial' (kappa > 0.7) for achalasia type I/II and no lower than 'fair-moderate' (kappa >0.34) for any diagnosis. Overall agreement was somewhat higher among those that had performed >400 studies (n = 9; kappa 0.55) and 'substantial' among experts involved in development of the Chicago Classification system (n = 4; kappa 0.66). This prospective, randomized, and blinded study reports an acceptable level of inter-observer agreement for HRM diagnoses across the full spectrum of esophageal motility disorders for a large group of clinicians working in a range of medical institutions. Suboptimal agreement for diagnosis of peristaltic motility disorders highlights contribution of objective HRM metrics. PMID:25185507

17. FFTF Authorization Agreement

SciTech Connect

DAUTEL, W.A.

2000-02-25

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.

18. Coefficients for Interrater Agreement.

ERIC Educational Resources Information Center

Zegers, Frits E.

1991-01-01

The degree of agreement between two raters rating several objects for a single characteristic can be expressed through an association coefficient, such as the Pearson product-moment correlation. How to select an appropriate association coefficient, and the desirable properties and uses of a class of such coefficients--the Euclidean…

19. Porcine arterivirus activates the NF-kappaB pathway through IkappaB degradation.

PubMed

Lee, Sang-Myeong; Kleiboeker, Steven B

2005-11-10

Nuclear factor-kappaB (NF-kappaB) 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-kappaB in MARC-145 cells and alveolar macrophages. In porcine reproductive and respiratory syndrome virus (PRRSV)-infected cells, NF-kappaB activation was characterized by translocation of NF-kappaB from the cytoplasm to the nucleus, increased DNA binding activity, and NF-kappaB-regulated gene expression. NF-kappaB activation was increased as PRRSV infection progressed and in a viral dose-dependent manner. UV-inactivation of PRRSV significantly reduced the level of NF-kappaB activation. Degradation of IkappaB protein was detected late in PRRSV infection, and overexpression of the dominant negative form of IkappaBalpha (IkappaBalphaDN) significantly suppressed NF-kappaB activation induced by PRRSV. However, IkappaBalphaDN 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-kappaB DNA binding activity in PRRSV-infected cells, suggesting ROS as a mechanism by which NF-kappaB was activated by PRRSV infection. Moreover, NF-kappaB-dependent expression of matrix metalloproteinase (MMP)-2 and MMP-9 was observed in PRRSV-infected cells, an observation which implies that NF-kappaB 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. PMID:16129468

20. 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. PMID:22232301

1. Kappa-opioid receptor signaling and brain reward function

PubMed Central

2009-01-01

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. PMID:19804796

2. 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

3. 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.

4. 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.

5. 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.

6. Countries renew rescue agreement

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.

7. Opioid binding properties of the purified kappa receptor from human placenta

SciTech Connect

Ahmed, M.S.; Zhou, D.; Cavinato, A.G.; Maulik, D.

1989-01-01

A glycoprotein with a molecular weight of 63,000 has been purified, in an active form, from human placental villus tissue membranes. The binding properties of this glycoprotein to opioid alkaloids and peptides indicates that it is the kappa opiate receptor of human placenta. The receptor binds the tritiated ligands etorphine, bremazocine, ethylketocyclazocine and naloxone specifically and reversibly with Kd values of 3.3, 4.4, 5.1 and 7.0nM, respectively. The binding of /sup 3/H-Bremazocine to the purified receptor is inhibited by the following compounds with the corresponding Ki values EKC, 1.3 x 10/sup -8/M; Dynorphin 1-8, 3.03 x 10/sup -7/; U50,488H, 4.48 x 10/sup -9/; U69-593,2.28 x 10/sup -8/, morphine, 4.05 x 10/sup -6/ DADLE, 6.47 x 10/sup -6/ and naloxone, 2.64 x 10/sup -8/. The purified receptor binds 8 nmole of /sup 3/H-Etorphine and 1.7 nmole /sup 3/H-BZC per mg protein. The theoretical binding capacity of a protein of this molecular weight is 15.8. Although the iodinated purified receptor appears by autoradiography as one band on SDS-PAGE, yet homogeneity of the preparation is not claimed.

8. Body Size Perceptions and Weight Status of Adults in a Nigerian Rural Community

PubMed Central

Akinpelu, AO; Oyewole, OO; Adekanla, BA

2015-01-01

Background: Overweight and obesity are now recognized worldwide as increasing public health problems throughout the life course and wrong perception of one's body size may reduce the motivation for an overweight person to lose weight. Aim: This study was conducted to investigate how Nigerian rural dwellers perceive their body size and how their perception agrees with their body mass index (BMI). Subjects and Methods: A cross-sectional sample of 183 adults living in a rural community, South-West Nigeria was randomly recruited into the study. Their verbal and visual body size perceptions were assessed through structured questions and body images. Descriptive and inferential statistics were used to analyze the data. Results: Thirty-five percent (64/183) of participants were classified as either overweight or obese by BMI. More than half of the participants perceived themselves as normal weight. More women perceived themselves to be obese than men in both verbal and visual perceptions. Based on BMI classification, 43% (79/183) and 54% (98/183) of participants misperceived themselves in verbal and visual perception, respectively. Underestimation of body size was higher in men (38.3%, 36/94) while overestimation was higher in women (9.0%, 8/89). Men had consistently higher values of kappa coefficient which indicate greater agreement than women in both types of perception. Conclusion: We found considerable gender differences in body weight perception of adults in the Nigerian rural community. A large proportion of these rural dwellers could not appropriately classify their weight status; and over 30% (64/183) and nearly 50% (92/183) of them underestimated their own body weight in verbal and visual perceptions respectively. PMID:26500794

9. Singaporean Mothers’ Perception of Their Three-year-old Child’s Weight Status: A Cross-Sectional Study

PubMed Central

Cheung, Yin Bun; Chan, Jerry Kok Yen; Tint, Mya Thway; Godfrey, Keith M.; Gluckman, Peter D.; Kwek, Kenneth; Saw, Seang Mei; Chong, Yap-Seng; Lee, Yung Seng; Yap, Fabian; Lek, Ngee

2016-01-01

Objective Inaccurate parental perception of their child’s weight status is commonly reported in Western countries. It is unclear whether similar misperception exists in Asian populations. This study aimed to evaluate the ability of Singaporean mothers to accurately describe their three-year-old child’s weight status verbally and visually. Methods At three years post-delivery, weight and height of the children were measured. Body mass index (BMI) was calculated and converted into actual weight status using International Obesity Task Force criteria. The mothers were blinded to their child’s measurements and asked to verbally and visually describe what they perceived was their child’s actual weight status. Agreement between actual and described weight status was assessed using Cohen’s Kappa statistic (κ). Results Of 1237 recruited participants, 66.4% (n = 821) with complete data on mothers’ verbal and visual perceptions and children’s anthropometric measurements were analysed. Nearly thirty percent of the mothers were unable to describe their child’s weight status accurately. In verbal description, 17.9% under-estimated and 11.8% over-estimated their child’s weight status. In visual description, 10.4% under-estimated and 19.6% over-estimated their child’s weight status. Many mothers of underweight children over-estimated (verbal 51.6%; visual 88.8%), and many mothers of overweight and obese children under-estimated (verbal 82.6%; visual 73.9%), their child’s weight status. In contrast, significantly fewer mothers of normal-weight children were inaccurate (verbal 16.8%; visual 8.8%). Birth order (p<0.001), maternal (p = 0.004) and child’s weight status (p<0.001) were associated with consistently inaccurate verbal and visual descriptions. Conclusions Singaporean mothers, especially those of underweight and overweight children, may not be able to perceive their young child’s weight status accurately. To facilitate prevention of childhood

10. Experienced and inexperienced observers achieved relatively high within-observer agreement on video mobility scoring of dairy cows.

PubMed

Garcia, E; König, K; Allesen-Holm, B H; Klaas, I C; Amigo, J M; Bro, R; Enevoldsen, C

2015-07-01

Assessment of lameness prevalence and severity requires visual evaluation of thelocomotion of a cow. Welfare schemes including locomotion assessments are increasingly being adopted, and more farmers and their veterinarians might implement a locomotion-scoring routine together. However, high within-observer agreement is a prerequisite for obtaining valid mobility scorings, and within-observer agreement cannot be estimated in a barn, because the gait of cows is dynamic and may change between 2 occasions. The objective of this study was to estimate the within-observer agreement according to the observers' educational background and experience with cattle, based on video recordings with very diverse types of gait. Groups of farmers, bovine veterinarians, first- and fourth-year veterinary students, researchers, and cattle-inexperienced sensory assessors evaluated mobility using a 5-point mobility score system developed specifically for walking cows (n=102 observers). The evaluation sessions were similar for all groups, lasted 75 min, and were organized as follows: introduction, test A, short training session, break, and test B. In total, video recordings of 22 cows were displayed twice in a random order (11 cows in each test × 2 replicates). Data were analyzed applying kappa coefficient, logistic regression, and testing for random effects of observers. The crude estimates of 95% confidence interval for weighted kappa in test A and B ranged, respectively, from 0.76 to 0.80 and 0.70 to 0.75. When adjusting for the fixed effects of video sample and gait scoring preferences, the probability of assigning the same mobility score twice to the same cow varied from 55% (sensory assessors) to 72% (fourth-year veterinary students). The random effect of the individual observers was negligible. That is, in general observers could categorize the mobility characteristics of cows quite well. Observers who preferred to assess the attributes back arch or the overall mobility score

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

PubMed Central

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

2016-01-01

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

12. 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

13. 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. PMID:27100526

14. 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.

15. 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.

16. 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.

17. {kappa}K{sup +{pi}-} vertex in light cone QCD sum rules

SciTech Connect

Baytemir, G.; Sarac, Y.; Yilmaz, O.

2010-05-01

In this work we study the {kappa}K{sup +{pi}-} vertex in the framework of light cone QCD sum rules. We predict the coupling constant g{sub {kappa}K}{sup +}{sub {pi}}{sup -} to be g{sub {kappa}K}{sup +}{sub {pi}}{sup -}=(6.0{+-}1.0) GeV and estimate the scalar f{sub 0}-{sigma} mixing angle from the experimental ratio g{sup 2}({kappa}{yields}K{pi})/g{sup 2}({sigma}{yields}{pi}{pi}).

18. Biologic sequelae of I{kappa}B kinase (IKK) inhibition in multiple myeloma: therapeutic implications.

PubMed

Hideshima, Teru; Chauhan, Dharminder; Kiziltepe, Tanyel; Ikeda, Hiroshi; Okawa, Yutaka; Podar, Klaus; Raje, Noopur; Protopopov, Alexei; Munshi, Nikhil C; Richardson, Paul G; Carrasco, Ruben D; Anderson, Kenneth C

2009-05-21

Nuclear factor-kappaB (NF-kappaB) has an important role in multiple myeloma (MM) cell pathogenesis in the context of the bone marrow (BM) microenvironment. In NF-kappaB signaling cascades, IkappaB kinase alpha (IKKalpha) and IKKbeta are key molecules that predominantly mediate noncanonical and canonical pathways, respectively. In this study, we examined the biologic sequelae of the inhibition of IKKalpha versus IKKbeta in MM cell lines. All MM cell lines have constitutive canonical NF-kappaB activity, and a subset of MM cell lines shows noncanonical NF-kappaB activity. Adhesion to BM stromal cells further activates both canonical and noncanonical NF-kappaB activity. IKKbeta inhibitor MLN120B blocks canonical pathway and growth of MM cell lines but does not inhibit the noncanonical NF-kappaB pathway. Although IKKalpha knockdown induces significant growth inhibition in the cell lines with both canonical and noncanonical pathways, it does not inhibit NF-kappaB activation. Importantly, IKKalpha down-regulation decreases expression of beta-catenin and aurora-A, which are known to mediate MM cell growth and survival. Finally, IKKbeta inhibitor enhances the growth inhibition triggered by IKKalpha down-regulation in MM cells with both canonical and noncanonical NF-kappaB activity. Combination therapy targeting these kinases therefore represents a promising treatment strategy in MM. PMID:19270264

19. Automated Coronary Artery Calcification Scoring in Non-Gated Chest CT: Agreement and Reliability

PubMed Central

Takx, Richard A. P.; de Jong, Pim A.; Leiner, Tim; Oudkerk, Matthijs; de Koning, Harry J.; Mol, Christian P.; Viergever, Max A.; Išgum, Ivana

2014-01-01

Objective To determine the agreement and reliability of fully automated coronary artery calcium (CAC) scoring in a lung cancer screening population. Materials and Methods 1793 low-dose chest CT scans were analyzed (non-contrast-enhanced, non-gated). To establish the reference standard for CAC, first automated calcium scoring was performed using a preliminary version of a method employing coronary calcium atlas and machine learning approach. Thereafter, each scan was inspected by one of four trained raters. When needed, the raters corrected initially automaticity-identified results. In addition, an independent observer subsequently inspected manually corrected results and discarded scans with gross segmentation errors. Subsequently, fully automatic coronary calcium scoring was performed. Agatston score, CAC volume and number of calcifications were computed. Agreement was determined by calculating proportion of agreement and examining Bland-Altman plots. Reliability was determined by calculating linearly weighted kappa (κ) for Agatston strata and intraclass correlation coefficient (ICC) for continuous values. Results 44 (2.5%) scans were excluded due to metal artifacts or gross segmentation errors. In the remaining 1749 scans, median Agatston score was 39.6 (P25–P75∶0–345.9), median volume score was 60.4 mm3 (P25–P75∶0–361.4) and median number of calcifications was 2 (P25–P75∶0–4) for the automated scores. The κ demonstrated very good reliability (0.85) for Agatston risk categories between the automated and reference scores. The Bland-Altman plots showed underestimation of calcium score values by automated quantification. Median difference was 2.5 (p25–p75∶0.0–53.2) for Agatston score, 7.6 (p25–p75∶0.0–94.4) for CAC volume and 1 (p25–p75∶0–5) for number of calcifications. The ICC was very good for Agatston score (0.90), very good for calcium volume (0.88) and good for number of calcifications (0.64). Discussion Fully automated

20. 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).

1. Diffusion Weighted MR Imaging of Primary and Recurrent Middle Ear Cholesteatoma: An Assessment by Readers with Different Expertise

PubMed Central

Elefante, A.; Cavaliere, M.; Russo, C.; Caliendo, G.; Marseglia, M.; Cicala, D.; Piccolo, D.; Di Lullo, A.; Brunetti, L.; Palma, A.; Iengo, M.; Brunetti, A.

2015-01-01

Introduction and Purpose. Diffusion weighted imaging (DWI) has been proven to be valuable in the diagnosis of middle ear cholesteatoma. The aims of our study were to evaluate the advantage of multi-shot turbo spin echo (MSh TSE) DWI compared to single-shot echo-planar (SSh EPI) DWI for the diagnosis of cholesteatoma. Material and Methods. Thirty-two patients with clinical suspicion of unilateral cholesteatoma underwent preoperative MRI (1.5T) with SSh EPI and MSh TSE. Images were separately analyzed by 4 readers with different expertise to confirm the presence of cholesteatoma. Sensitivity, specificity, diagnostic accuracy, and positive (PPV) and negative predictive values (NPV) were assessed for each observer and interrater agreement was assessed using kappa statistics. Diagnosis was obtained at surgery. Results. Overall MSh TSE showed higher diagnostic accuracy and lower negative predictive value (NPV) compared to conventional SSh EPI. Interreader agreement between the observers revealed the superiority of MSh TSE compared to SSh EPI. Interrater agreement among all the four observers was higher by using MSh TSE compared to SSh EPI. Conclusion. Our findings suggest that MSh TSE DWI has higher sensitivity for detection of cholesteatoma and lower probability of misdiagnosis. MSh TSE DWI is useful in guiding less experienced observers to the diagnosis. PMID:25722983

2. Utility of 3D SPACE T2-weighted volumetric sequence in the localization of spinal dural arteriovenous fistula.

PubMed

Kannath, Santhosh Kumar; Alampath, Praveen; Enakshy Rajan, Jayadevan; Thomas, Bejoy; Sankara Sarma, P; Tirur Raman, Kapilamoorthy

2016-07-01

OBJECTIVE The aim of this study was to investigate the utility of a heavily T2-weighted volumetric MRI sequence (3D sampling perfection with application-optimized contrasts using different flip-angle evolutions [SPACE]) in the feeder localization of spinal dural arteriovenous fistula (SDAVF). METHODS Patients who were diagnosed with SDAVF and who had 3D SPACE source images available for review were identified from a retrospective review of medical records. A total of 16 patients were identified, and MR images were analyzed separately by 2 blinded observers. The accuracy of the observation and interobserver agreement were measured by Kendall's tau and kappa statistics. RESULTS The site of fistula was accurately predicted by Observers 1 and 2 in 81% and 88% of cases, respectively, which improved to 94% when the level was considered within 1 vertebral level. The observer agreement with gold-standard angiography and interobserver agreement were found to be highly significant (p < 0.0001). CONCLUSIONS The 3D SPACE MRI sequence is valuable in the precise detection of the site of SDAVF. It may help to tailor digital subtraction angiography and thereby reduce the radiation exposure, contrast load, and study time. PMID:26943253

3. 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

4. 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.

5. Substantial Agreement of Referee Recommendations at a General Medical Journal – A Peer Review Evaluation at Deutsches Ärzteblatt International

PubMed Central

Baethge, Christopher; Franklin, Jeremy; Mertens, Stephan

2013-01-01

Background Peer review is the mainstay of editorial decision making for medical journals. There is a dearth of evaluations of journal peer review with regard to reliability and validity, particularly in the light of the wide variety of medical journals. Studies carried out so far indicate low agreement among reviewers. We present an analysis of the peer review process at a general medical journal, Deutsches Ärzteblatt International. Methodology/Principal Findings 554 reviewer recommendations on 206 manuscripts submitted between 7/2008 and 12/2009 were analyzed: 7% recommended acceptance, 74% revision and 19% rejection. Concerning acceptance (with or without revision) versus rejection, there was a substantial agreement among reviewers (74.3% of pairs of recommendations) that was not reflected by Fleiss' or Cohen's kappa (<0.2). The agreement rate amounted to 84% for acceptance, but was only 31% for rejection. An alternative kappa-statistic, however, Gwet's kappa (AC1), indicated substantial agreement (0.63). Concordance between reviewer recommendation and editorial decision was almost perfect when reviewer recommendations were unanimous. The correlation of reviewer recommendations and citations as counted by Web of Science was low (partial correlation adjusted for year of publication: −0.03, n.s.). Conclusions/Significance Although our figures are similar to those reported in the literature our conclusion differs from the widely held view that reviewer agreement is low: Based on overall agreement we consider the concordance among reviewers sufficient for the purposes of editorial decision making. We believe that various measures, such as positive and negative agreement or alternative Kappa values are superior to the application of Cohen's or Fleiss' Kappa in the analysis of nominal or ordinal level data regarding reviewer agreement. Also, reviewer recommendations seem to be a poor proxy for citations because, for example, manuscripts will be changed considerably

6. University-Industry Teaming Agreements.

ERIC Educational Resources Information Center

Stombler, Milton P.

1989-01-01

The use of preaward agreements between the industry and the university collaborating to seek external funding, particularly from government sources, is examined. The agreements describe the parties' obligations in seeking funding and lay the groundwork for subsequent research agreements. Elements of such agreements are discussed to raise awareness…

7. Bis(acesulfamato-kappa2N3,O4)bis(2-aminopyrimidine-kappaN1)copper(II).

PubMed

Bulut, Ahmet; Içbudak, Hasan; Sezer, Gözde; Kazak, Canan

2005-05-01

In the crystal structure of the title compound, bis(2-aminopyrimidine-kappaN1)bis[6-methyl-1,2,3-oxathiazin-4(3H)-one 2,2-dioxide(1-)-kappa2N3,O4]copper(II), [Cu(C4H4NO4S)2(C4H5N3)2], the first mixed-ligand complex of acesulfame, the CuII centre resides on a centre of symmetry and has an octahedral geometry that is distorted both by the presence of four-membered chelate rings and by the Jahn-Teller effect. The equatorial plane is formed by the N atoms of two aminopyrimidine (ampym) ligands and by the weakly basic carbonyl O atoms of the acesulfamate ligands, while the more basic deprotonated N atoms of these ligands are in the elongated axial positions with a strong misdirected valence. The crystal is stabilized by pyrimidine ring stacking and by intermolecular hydrogen bonding involving the NH2 moiety of the ampym ligand and the carbonyl O atom of the acesulfamate moiety. PMID:15876705

8. 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

9. 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

10. A 90-day dietary study on kappa carrageenan with emphasis on the gastrointestinal tract.

PubMed

Weiner, Myra L; Nuber, David; Blakemore, William R; Harriman, Jay F; Cohen, Samuel M

2007-01-01

Groups of Fischer 344 rats (20/sex/group) received control or treated diets at levels of 0, 25,000 or 50,000 ppm kappa carrageenan with a molecular weight range (Mw) of 196,000-257,000 Da for 90 days. The Low Molecular Weight Tail (LMT) ranged between 1.9% and 12.0%<50 kDa (mean 7%) based on the results of a program initiated to develop a validated analytical method to measure the LMT. This is the first GLP dietary study in which carrageenan is characterized by percentage LMT. Clinical examinations were performed daily. Individual food consumption/body weight measurements were made weekly. Ophthalmic exam was conducted prior to and at the end of treatment. Hematology/serum chemistry and urinalysis evaluations were done at necropsy, as were organ weight determinations for adrenals, brain, heart, kidneys, liver, ovaries, spleen, testes and thyroid with parathyroids. Full histopathological evaluation of organs was conducted on the control and 50,000 ppm groups, including hematoxylin-eosin-stained cross sections of paraffin-embedded rolled colon. Clinical signs were limited to soft feces in high dose rats and to a lesser extent in low dose rats. There were no treatment-related effects on body weights, urinalysis, hematology or clinical chemistry parameters, or on organ weights or ophthalmic, macroscopic or microscopic findings. The gastrointestinal tract appeared normal in detailed histopathological evaluation using the Swiss roll technique. The NOAEL is 50,000 ppm in the diet (mean calculated test material consumption of 3394+/-706 mg/kg/day in males, 3867+/-647 mg/kg/day in females). The results of the study provide evidence that it is not necessary to characterize carrageenan by a specification for LMT (less than 5% below 50 kDa) as has been done in Commission Directive 2004/45/EC of 16 April 2004 (Commission Directive, 2004/45/EC of 16 April 2004 amending Directive 96/77/EC laying down specific purity criteria on food additives other than colors and sweeteners

11. Behavioral meaningful opioidergic stimulation activates kappa receptor gene expression

PubMed Central

Teodorov, E.; Ferrari, M.F.R.; Fior-Chadi, D.R.; Camarini, R.; Felício, L.F.

2012-01-01

The periaqueductal gray (PAG) has been reported to be a location for opioid regulation of pain and a potential site for behavioral selection in females. Opioid-mediated behavioral and physiological responses differ according to the activity of opioid receptor subtypes. The present study investigated the effects of the peripheral injection of the kappa-opioid receptor agonist U69593 into the dorsal subcutaneous region of animals on maternal behavior and on Oprk1 gene activity in the PAG of female rats. Female Wistar rats weighing 200-250 g at the beginning of the study were randomly divided into 2 groups for maternal behavior and gene expression experiments. On day 5, pups were removed at 7:00 am and placed in another home cage that was distant from their mother. Thirty minutes after removing the pups, the dams were treated with U69593 (0.15 mg/kg, sc) or 0.9% saline (up to 1 mL/kg) and after 30 min were evaluated in the maternal behavior test. Latencies in seconds for pup retrieval, grouping, crouching, and full maternal behavior were scored. The results showed that U69593 administration inhibited maternal behavior (P < 0.05) because a lower percentage of U69593 group dams showed retrieval of first pup, retrieving all pups, grouping, crouching and displaying full maternal behavior compared to the saline group. Opioid gene expression was evaluated using real-time reverse-transcription polymerase chain reaction (RT-PCR). A single injection of U69593 increased Oprk1 PAG expression in both virgin (P < 0.05) and lactating female rats (P < 0.01), with no significant effect on Oprm1 or Oprd1 gene activity. Thus, the expression of kappa-opioid receptors in the PAG may be modulated by single opioid receptor stimulation and behavioral meaningful opioidergic transmission in the adult female might occur simultaneously to specific changes in gene expression of kappa-opioid receptor subtype. This is yet another alert for the complex role of the opioid system in female

12. 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

13. 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

14. 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

15. 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.

16. 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.

17. 40 CFR 721.1880 - Borate(1-), tris(acetato-.kappa.O)hydro-, sodium, (T-4)-.

Code of Federal Regulations, 2010 CFR

2010-07-01

... New Uses for Specific Chemical Substances § 721.1880 Borate(1-), tris(acetato-.kappa.O)hydro-, sodium... substance identified as borate(1-), tris(acetato-.kappa.O)hydro-, sodium, (T-4)- (PMN P-00-0922; CAS No... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Borate(1-),...

18. 40 CFR 721.1880 - Borate(1-), tris(acetato-.kappa.O)hydro-, sodium, (T-4)-.

Code of Federal Regulations, 2013 CFR

2013-07-01

... New Uses for Specific Chemical Substances § 721.1880 Borate(1-), tris(acetato-.kappa.O)hydro-, sodium... substance identified as borate(1-), tris(acetato-.kappa.O)hydro-, sodium, (T-4)- (PMN P-00-0922; CAS No... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Borate(1-),...

19. 40 CFR 721.1880 - Borate(1-), tris(acetato-.kappa.O)hydro-, sodium, (T-4)-.

Code of Federal Regulations, 2012 CFR

2012-07-01

... New Uses for Specific Chemical Substances § 721.1880 Borate(1-), tris(acetato-.kappa.O)hydro-, sodium... substance identified as borate(1-), tris(acetato-.kappa.O)hydro-, sodium, (T-4)- (PMN P-00-0922; CAS No... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Borate(1-),...

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

Code of Federal Regulations, 2011 CFR

2011-07-01

... New Uses for Specific Chemical Substances § 721.1880 Borate(1-), tris(acetato-.kappa.O)hydro-, sodium... substance identified as borate(1-), tris(acetato-.kappa.O)hydro-, sodium, (T-4)- (PMN P-00-0922; CAS No... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Borate(1-),...

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

Code of Federal Regulations, 2014 CFR

2014-07-01

... New Uses for Specific Chemical Substances § 721.1880 Borate(1-), tris(acetato-.kappa.O)hydro-, sodium... substance identified as borate(1-), tris(acetato-.kappa.O)hydro-, sodium, (T-4)- (PMN P-00-0922; CAS No... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Borate(1-),...

2. Schnitzler's syndrome with IgG kappa gammopathy.

PubMed

Akimoto, Ruri; Yoshida, Masami; Matsuda, Rie; Miyasaka, Keiichi; Itoh, Masatoshi

2002-11-01

A seventy-year-old man with a variant type of Schnitzler's syndrome is reported. Physical examination showed pruritic urticarial lesions on the extremities, arthralgia of knee joints, and intermittent fever. Laboratory investigations revealed a high level of IgG, an increased enythrocyte sedimentation rate, urinary Bence-Jones protein, and an M-bow in serum protein electrophoresis, which was shown to be a monoclonal IgG kappa type. Histological examination showed perivascular neutrophil and lymphocytic infiltration into the upper dermis and diffuse neutrophilic infiltration in the middle dermis. One of the clinical features of typical Schnitzler's syndrome is IgM macroglobulinemia, and this is a very rare case of this syndrome with IgG gammopathy. PMID:12484437

3. Nuclear factor kappa B role in inflammation associated gastrointestinal malignancies

PubMed Central

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

2015-01-01

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

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

SciTech Connect

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)].

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

2015-11-01

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. 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.

7. Scuba Weights

NASA Technical Reports Server (NTRS)

1995-01-01

The Attitude Adjuster is a system for weight repositioning corresponding to a SCUBA diver's changing positions. Compact tubes on the diver's air tank permit controlled movement of lead balls within the Adjuster, automatically repositioning when the diver changes position. Manufactured by Think Tank Technologies, the system is light and small, reducing drag and energy requirements and contributing to lower air consumption. The Mid-Continent Technology Transfer Center helped the company with both technical and business information and arranged for the testing at Marshall Space Flight Center's Weightlessness Environmental Training Facility for astronauts.

8. Evaluation of Spatial Agreement of Distinct Landslide Prediction Models

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

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

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.

10. Comment on 'Mathematical and physical aspects of Kappa velocity distribution' [Phys. Plasmas 14, 110702 (2007)

SciTech Connect

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

2009-09-15

A recent paper [L.-N. Hau and W.-Z. Fu, Phys. Plasmas 14, 110702 (2007)] deals with certain mathematical and physical properties of the kappa distribution. We comment on the authors' use of a form of distribution function that is different from the 'standard' form of the kappa distribution, and hence their results, inter alia for an expansion of the distribution function and for the associated number density in an electrostatic potential, do not fully reflect the dependence on {kappa} that would be associated with the conventional kappa distribution. We note that their definition of the kappa distribution function is also different from a modified distribution based on the notion of nonextensive entropy.

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

NASA Technical Reports Server (NTRS)

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

1995-01-01

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

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

SciTech Connect

Duxbury, Mark S.; Whang, Edward E. . E-mail: ewhang1@partners.org

2007-03-02

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

13. Bortezomib induces canonical nuclear factor-kappaB activation in multiple myeloma cells.

PubMed

Hideshima, Teru; Ikeda, Hiroshi; Chauhan, Dharminder; Okawa, Yutaka; Raje, Noopur; Podar, Klaus; Mitsiades, Constantine; Munshi, Nikhil C; Richardson, Paul G; Carrasco, Ruben D; Anderson, Kenneth C

2009-07-30

Bortezomib is a proteasome inhibitor with remarkable preclinical and clinical antitumor activity in multiple myeloma (MM) patients. The initial rationale for its use in MM was inhibition of nuclear factor (NF)-kappaB activity by blocking proteasomal degradation of inhibitor of kappaBalpha (IkappaBalpha). Bortezomib inhibits inducible NF-kappaB activity; however, its impact on constitutive NF-kappaB activity in MM cells has not yet been defined. In this study, we demonstrate that bortezomib significantly down-regulated IkappaBalpha expression and triggered NF-kappaB activation in MM cell lines and primary tumor cells from MM patients. Importantly, no inhibition of p65 (RelA) nuclear translocation was recognized after bortezomib treatment in a murine xenograft model bearing human MM cells. Bortezomib-induced NF-kappaB activation was mediated via the canonical pathway. Moreover, other classes of proteasome inhibitors also induced IkappaBalpha down-regulation associated with NF-kappaB activation. Molecular mechanisms whereby bortezomib induced IkappaBalpha down-regulation were further examined. Bortezomib triggered phosphorylation of IkappaB kinase (IKKbeta) and its upstream receptor-interacting protein 2, whereas IKKbeta inhibitor MLN120B blocked bortezomib-induced IkappaBalpha down-regulation and NF-kappaB activation, indicating receptor-interacting protein 2/IKKbeta signaling plays crucial role in bortezomib-induced NF-kappaB activation. Moreover, IKKbeta inhibitors enhanced bortezomib-induced cytotoxicity. Our studies therefore suggest that bortezomib-induced cytotoxicity cannot be fully attributed to inhibition of canonical NF-kappaB activity in MM cells. PMID:19436050

14. 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

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. 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

17. 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.…

18. 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…

19. 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

20. 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.

1. 1,25-Dihydroxyvitamin D{sub 3} induces biphasic NF-{kappa}B responses during HL-60 leukemia cells differentiation through protein induction and PI3K/Akt-dependent phosphorylation/degradation of I{kappa}B

SciTech Connect

Tse, A.K.-W.; Wan, C.-K.; Shen, X.-L.; Zhu, G.-Y.; Cheung, H.-Y.; Yang, M.; Fong, W.-F. . E-mail: wffong@hkbu.edu.hk

2007-05-01

1,25-Dihydroxyvitamin D{sub 3} (VD{sub 3}) induces differentiation in a number of leukemia cell lines and under various conditions is able to either stimulate or inhibit nuclear factor kappa B (NF-{kappa}B) activity. Here we report a time-dependent biphasic regulation of NF-{kappa}B in VD{sub 3}-treated HL-60 leukemia cells. After VD{sub 3} treatment there was an early {approx} 4 h suppression and a late 8-72 h prolonged reactivation of NF-{kappa}B. The reactivation of NF-{kappa}B was concomitant with increased IKK activities, IKK-mediated I{kappa}B{alpha} phosphorylation, p65 phosphorylation at residues S276 and S536, p65 nuclear translocation and p65 recruitment to the NF-{kappa}B/vitamin D responsive element promoters. In parallel with NF-{kappa}B stimulation, there was an up-regulation of NF-{kappa}B controlled inflammatory and anti-apoptotic genes such as TNF{alpha}, IL-1{beta} and Bcl-xL. VD{sub 3}-triggered reactivation of NF-{kappa}B was associated with PI3K/Akt phosphorylation. PI3K/Akt antagonists suppressed VD{sub 3}-stimulated I{kappa}B{alpha} phosphorylation as well as NF-{kappa}B-controlled gene expression. The early {approx} 4 h VD{sub 3}-mediated NF-{kappa}B suppression coincided with a prolonged increase of I{kappa}B{alpha} protein which require de novo protein synthesis, lasted for as least 72 h and was insensitive to MAPK, IKK or PI3K/Akt inhibitors. Our data suggest a novel biphasic regulation of NF-{kappa}B in VD{sub 3}-treated leukemia cells and our results may have provided the first molecular explanation for the contradictory observations reported on VD{sub 3}-mediated immune-regulation.

2. Small interfering RNA targeting of Recepteur d'Origine Nantais induces apoptosis via modulation of nuclear factor-kappaB and Bcl-2 family in gastric cancer cells.

PubMed

Park, Jung Sun; Park, Ji Hye; Lee, Soong; Joo, Young Eun; Jung, Young Do

2010-09-01

The abnormal accumulation and activation of the receptor tyrosine kinase, Recepteur d'Origine Nantais (RON), has been implicated in tumorigenesis and metastasis in epithelial tumors including gastric cancer. This study examined whether the sequence-specific small interfering RNA (siRNA) suppression of the RON expression could induce apoptotic cell death, and investigated the involved molecular mechanisms. Sequence-specific siRNA effectively suppressed the RON expression at both the mRNA and protein levels. Silencing of the RON expression significantly inhibited gastric cancer cell proliferation and induced apoptosis in a time-dependent manner. The induction of apoptosis was confirmed by the ladder-patterned DNA fragmentation, the presence of cleaved and condensed nuclear chromatin and the increased number of annexin V-positive cells. RON-targeted siRNA effectively inhibited the constitutive nuclear factor-kappaB (NF-kappaB) activation as revealed by an altered electrophoretic mobility shift. In agreement with this, silencing of the RON expression resulted in a decrease in the nuclear level of the p65 subunit of NF-kappaB. The transfection of siRNA, which blocked the RON expression, also caused a change in the ratio of Bax/Bcl-2 in a manner that favored apoptosis. The siRNA silencing of RON induced cytochrome c release and the activation of caspase-8 and caspase-9. These results indicate that RON-targeted siRNA could be therapeutically efficacious by inducing cell apoptosis through the modulation of the NF-kappaB and Bcl-2 family in gastric cancer cells. PMID:20664977

3. Characterization of a mutant cell line that does not activate NF-kappaB in response to multiple stimuli.

PubMed Central

Courtois, G; Whiteside, S T; Sibley, C H; Israel, A

1997-01-01

Numerous genes required during the immune or inflammation response as well as the adhesion process are regulated by nuclear factor kappaB (NF-kappaB). Associated with its inhibitor, I kappaB, NF-kappaB resides as an inactive form in the cytoplasm. Upon stimulation by various agents, I kappaB is proteolyzed and NF-kappaB translocates to the nucleus, where it activates its target genes. The transduction pathways that lead to I kappaB inactivation remain poorly understood. In this study, we have characterized a cellular mutant, the 70/Z3-derived 1.3E2 murine pre-B cell line, that does not activate NF-kappaB in response to several stimuli. We demonstrate that upon stimulation by lipopolysaccharide, Taxol, phorbol myristate acetate, interleukin-1, or double-stranded RNA, I kappaB alpha is not degraded, as a result of an absence of induced phosphorylation on serines 32 and 36. Neither a mutation in I kappaB alpha nor a mutation in p50 or relA, the two major subunits of NF-kappaB in this cell line, accounts for this phosphorylation defect. As well as culminating in the inducible phosphorylation of I kappaB alpha on serines 32 and 36, all the stimuli that are inactive on 1.3E2 cells exhibit a sensitivity to the antioxidant pyrrolidine dithiocarbamate (PDTC). In contrast, stimuli such as hyperosmotic shock or phosphatase inhibitors, which use PDTC-insensitive pathways, induce I kappaB alpha degradation in 1.3E2. Analysis of the redox status of 1.3E2 does not reveal any difference from wild-type 70Z/3. We also report that the human T-cell leukemia virus type 1 (HTLV-1)-derived Tax trans-activator induces NF-kappaB activity in 1.3E2, suggesting that this viral protein does not operate via the defective pathway. Finally, we show that two other I kappaB molecules, I kappaB beta and the recently identified I kappaB epsilon, are not degraded in the 1.3E2 cell line following stimulation. Our results demonstrate that 1.3E2 is a cellular transduction mutant exhibiting a defect in a

4. Different electronic transport regimes in the quasi-two-dimensional organic conductors {kappa}(BEDT-TTF){<_2}X.

SciTech Connect

Muller, J.; Brandenburg, J.; Schweitzer, D.; Schlueter, J. A.

2012-05-01

We study the low-frequency dynamical properties of correlated charge carriers in various of the quasi-two-dimensional organic charge-transfer salts {kappa}-(BEDT-TTF){sub 2}X by means of fluctuation (noise) spectroscopy. Close to the critical endpoint of the Mott metal-insulator transition, a pronounced increase of the 1/f-noise level accompanied by a substantial shift of spectral weight to low frequencies indicates a sudden increase of the time scale of the charge fluctuations. For the less correlated, more metallic materials, we find a crossover/transition from hopping transport of more-or-less localized carriers at elevated temperatures to a low-temperature regime, where a metallic coupling of the layers allows for coherent interlayer transport of delocalized electrons.

5. CTGF promotes inflammatory cell infiltration of the renal interstitium by activating NF-kappaB.

PubMed

Sánchez-López, Elsa; Rayego, Sandra; Rodrigues-Díez, Raquel; Rodriguez, Javier Sánchez; Rodrigues-Díez, Raúl; Rodríguez-Vita, Juan; Carvajal, Gisselle; Aroeira, Luiz Stark; Selgas, Rafael; Mezzano, Sergio A; Ortiz, Alberto; Egido, Jesús; Ruiz-Ortega, Marta

2009-07-01

Connective tissue growth factor (CTGF) is an important profibrotic factor in kidney diseases. Blockade of endogenous CTGF ameliorates experimental renal damage and inhibits synthesis of extracellular matrix in cultured renal cells. CTGF regulates several cellular responses, including adhesion, migration, proliferation, and synthesis of proinflammatory factors. Here, we investigated whether CTGF participates in the inflammatory process in the kidney by evaluating the nuclear factor-kappa B (NF-kappaB) pathway, a key signaling system that controls inflammation and immune responses. Systemic administration of CTGF to mice for 24 h induced marked infiltration of inflammatory cells in the renal interstitium (T lymphocytes and monocytes/macrophages) and led to elevated renal NF-kappaB activity. Administration of CTGF increased renal expression of chemokines (MCP-1 and RANTES) and cytokines (INF-gamma, IL-6, and IL-4) that recruit immune cells and promote inflammation. Treatment with a NF-kappaB inhibitor, parthenolide, inhibited CTGF-induced renal inflammatory responses, including the up-regulation of chemokines and cytokines. In cultured murine tubuloepithelial cells, CTGF rapidly activated the NF-kappaB pathway and the cascade of mitogen-activated protein kinases, demonstrating crosstalk between these signaling pathways. CTGF, via mitogen-activated protein kinase and NF-kappaB activation, increased proinflammatory gene expression. These data show that in addition to its profibrotic properties, CTGF contributes to the recruitment of inflammatory cells in the kidney by activating the NF-kappaB pathway. PMID:19423687

6. 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.

7. NF-kappaB and cancer: how intimate is this relationship.

PubMed

Prasad, Sahdeo; Ravindran, Jayaraj; Aggarwal, Bharat B

2010-03-01

NF-kappaB, a transcription factor first discovered in 1986, is now known to be closely connected to the process of tumorogenesis based on a multiplicity of evidence. (1) NF-kappaB is activated in response to tobacco, stress, dietary agents, obesity, alcohol, infectious agents, irradiation, and environmental stimuli that account for as much as 95% of all cancers. (2) The transcription factor has been linked with transformation of cells. (3) It is constitutively active in most tumor cells. (4) It has also been linked with the survival of cancer stem cells, an early progenitor cell that has acquired self-renewal potential. (5) NF-kappaB regulates the expression of most anti-apoptotic gene products associated with the survival of the tumor. (6) It also regulates the gene products linked with proliferation of tumors. (7) The transcription factor controls the expression of gene products linked with invasion, angiogenesis, and metastasis of cancer. (8) While most carcinogens activate NF-kappaB, most chemopreventive agents suppress its activation. These observations suggest that NF-kappaB is intimately intertwined with cancer growth and metastasis. The mechanism that leads to constitutive activation of NF-kappaB in hematological, gastrointestinal, genitourinary, gynecological, thoracic head and neck, breast, and skin cancers, and the ways NF-kappaB is activated are the topics of discussion in this review. PMID:19823771

8. 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.

9. The Ig kappa 3' enhancer is activated by gradients of chromatin accessibility and protein association.

PubMed

McDevit, Daniel C; Perkins, Leslie; Atchison, Michael L; Nikolajczyk, Barbara S

2005-03-01

The Igkappa locus is recombined following initiation of a signaling cascade during the early pre-B stage of B cell development. The Ig kappa3' enhancer plays an important role in normal B cell development by regulating kappa locus activation. Quantitative analyses of kappa3' enhancer chromatin structure by restriction endonuclease accessibility and protein association by chromatin immunoprecipitation in a developmental series of primary murine B cells and murine B cell lines demonstrate that the enhancer is activated progressively through multiple steps as cells mature. Moderate kappa3' chromatin accessibility and low levels of protein association in pro-B cells are increased substantially as the cells progress from pro- to pre-B, then eventually mature B cell stages. Chromatin immunoprecipitation assays suggest transcriptional regulators of the kappa3' enhancer, specifically PU.1 and IFN regulatory factor-4, exploit enhanced accessibility by increasing association as cells mature. Characterization of histone acetylation patterns at the kappa3' enhancer and experimental inhibition of histone deacetylation suggest changes therein may determine changes in enzyme and transcription factor accessibility. This analysis demonstrates kappa activation is a multistep process initiated in early B cell precursors before Igmu recombination and finalized only after the pre-B cell stage. PMID:15728493

10. 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.

11. 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.

12. Induction of carcinoma cell migration on vitronectin by NF-kappa B-dependent gene expression.

PubMed Central

Yebra, M; Filardo, E J; Bayna, E M; Kawahara, E; Becker, J C; Cheresh, D A

1995-01-01

Integrin alpha v beta 5 promotes FG carcinoma cell adhesion to vitronectin yet requires protein kinase C (PKC) activation for migration on this ligand. Here we report that this PKC-dependent cell motility event requires NF-kappaB-dependent transcription. Specifically, a component within nuclear extracts prepared from PKC-stimulated FG cells exhibited a significant increase in binding activity to a synthetic oligonucleotide containing a consensus kappa B sequence. These nuclear DNA-binding complexes were shown to be comprised of p65 and p50 NF-kappaB/rel family members and appeared functionally active because they promoted transcription of a reporter construct containing a kappa B site. The NF-kappa B activation event was directly linked to the alpha v beta 5 motility response because the NF-kappa B-binding oligonucleotide, when introduced into FG cells, inhibited cell migration on vitronectin but not on collagen and had no effect on cell adhesion to either ligand. These results suggest that the detected DNA-binding complexes interact with kappa B transcriptional elements to regulate gene expression required for alpha v beta 5-dependent cell motility on vitronectin. Images PMID:7579698

13. 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.

14. Quasi-Conformality of a Non-Extensive Entropy and Kappa Distributions

Kalogeropoulos, N.

2014-12-01

The Havrda-Charvat/Daroczy/Cressie-Read/Tsallis entropy has attracted substantial attention in the Physics literature during the last 25 years. It is intimately related to the kappa distributions that are of great interest in Plasma Physics. One of the most important questions in these investigations is the microscopic origin and ab initio determination of the kappa/non-extensive parameter that appears in these distributions. To determine its origin, it may be beneficial to explore some of the formal properties of the underlying entropic functional. Initial numerical, and mostly circumstantial, evidence points toward symmetries of the kappa parameter exhibited by systems described by this kappa ("Tsallis") entropy. Such symmetries are reminiscent of the conformal symmetries which are present in numerous cases of Physical interest such as second order phase transitions. In this exposition, we explore the origin of this conjectured symmetry of the kappa/non-extensive parameter. Our treatment relies in an essential way on the (quasi-) conformal properties of the kappa/Tsallis entropic functional and its related equilibrium kappa/q-exponential distributions.

15. Tumor marker nucleoporin 88 kDa regulates nucleocytoplasmic transport of NF-{kappa}B

SciTech Connect

Takahashi, Nozomi Kilsdonk, Jeroen W.J. van; Ostendorf, Benedikt; Smeets, Ruben; Bruggeman, Sophia W.M.; Alonso, Angel; Loo, Fons van de; Schneider, Matthias; Berg, Wim B. van den; Swart, Guido W.M.

2008-09-26

Nucleoporin 88 kDa (Nup88) is a tumor marker, overexpressed in various types of cancer. In Drosophila Nup88 (mbo) was reported to selectively mediate the nucleocytoplasmic transport of NF-{kappa}B, an ubiquitous transcription factor involved in immune responses, apoptosis, and cancer. We addressed the function of Nup88 in mammalian cells. Selective depletion of Nup88 by small interfering RNA (siRNA) inhibited NF-{kappa}B-dependent reporter gene activation and the nuclear translocation of NF-{kappa}B without affecting the upstream activation pathway in NIH3T3 cells. In contrast, nuclear translocation of glucocorticoid receptor was not reduced by the depletion of Nup88. In metastatic melanoma cells overexpressing Nup88, constitutive activation of NF-{kappa}B was found both in nucleus and cytoplasm. Nup88 depletion in these cells reduced TNF-induced nuclear accumulation of NF-{kappa}B subunits. We conclude that Nup88 regulates the activity of NF-{kappa}B at the level of nucleocytoplasmic transport. Overexpression of Nup88 in tumor cells may, thus be involved in the constitutive NF-{kappa}B activation.

16. Rapid weight loss

MedlinePlus

... loss-rapid weight loss; Overweight-rapid weight loss; Obesity-rapid weight loss; Diet-rapid weight loss ... for people who have health problems because of obesity. For these people, losing a lot of weight ...

17. Pregnancy Weight Gain Calculator

MedlinePlus

... Newsroom Dietary Guidelines Communicator’s Guide Pregnancy Weight Gain Calculator You are here Home / Online Tools Pregnancy Weight Gain Calculator Print Share Pregnancy Weight Gain Calculator Pregnancy Weight Gain Calculator Pregnancy Weight Gain Intro ...

18. Synergistic activation of NF-kappaB by nontypeable Haemophilus influenzae and tumor necrosis factor alpha.

PubMed

Watanabe, Takahiro; Jono, Hirofumi; Han, Jiahuai; Lim, David J; Li, Jian-Dong

2004-03-01

Nontypeable Haemophilus influenzae (NTHi) is an important human pathogen causing otitis media in children and exacerbation of chronic obstructive pulmonary disease in adults. Like most other bacterial infections, NTHi infections are also characterized by inflammation, which is mainly mediated by cytokines and chemokines such as tumor necrosis factor alpha (TNF-alpha). Among a variety of transcription regulators, NF-kappaB has been shown to play a critical role in regulating the expression of large numbers of genes encoding inflammatory mediators. In review of the current studies on NF-kappaB regulation, most of them have focused on investigating how NF-kappaB is activated by a single inducer at a time. However, in bacteria-induced inflammation in vivo, multiple inducers including both exogenous and endogenous mediators are present simultaneously. A key issue that has yet to be addressed is whether the exogenous inducers such as NTHi and the endogenous factors such as TNF-alpha activate NF-kappaB in a synergistic manner. We show that NTHi and TNF-alpha, when present together, synergistically induce NF-kappaB activation via two distinct signaling pathways: NF-kappaB translocation-dependent and -independent pathways. The NF-kappaB translocation-dependent pathway involves NF-kappaB-inducing kinase-IkappaB kinase beta/gamma-dependent phosphorylation and degradation of IkappaBalpha, whereas the NF-kappaB translocation-independent pathway involves mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase kinase kinase 1-dependent activation of MAPK kinase 3/6-p38 MAPK pathway. In addition, the same signaling pathways are also involved in synergistic induction of TNF-alpha, IL-1beta, and IL-8. These studies should deepen our understanding of the molecular mechanisms underlying the combinatorial regulation of inflammation and lead to development of therapeutic strategies for NTHi-induced infections. PMID:14993593

19. 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.

20. Two structurally distinct {kappa}B sequence motifs cooperatively control LPS-induced KC gene transcription in mouse macrophages

SciTech Connect

Ohmori, Y.; Fukumoto, S.; Hamilton, T.A.

1995-10-01

The mouse KC gene is an {alpha}-chemokine gene whose transcription is induced in mononuclear phagocytes by LPS. DNA sequences necessary for transcriptional control of KC by LPS were identified in the region flanking the transcription start site. Transient transfection analysis in macrophages using deletion mutants of a 1.5-kb sequence placed in front of the chloramphenicol acetyl transferase (CAT) gene identified an LPS-responsive region between residues -104 and +30. This region contained two {kappa}B sequence motifs. The first motif (position -70 to -59, {kappa}B1) is highly conserved in all three human GRO genes and in the mouse macrophage inflammatory protein-2 (MIP-2) gene. The second {kappa}B motif (position -89 to -78, {kappa}B2) was conserved only between the mouse and the rat KC genes. Consistent with previous reports, the highly conserved {kappa}B site ({kappa}B1) was essential for LPS inducibility. Surprisingly, the distal {kappa}B site ({kappa}B2) was also necessary for optimal response; mutation of either {kappa}B site markedly reduced sensitivity to LPS in RAW264.7 cells and to TNF-{alpha} in NIH 3T3 fibroblasts. Although both {kappa}B1 and {kappa}B2 sequences were able to bind members of the Rel homology family, including NF{kappa}B1 (P50), RelA (65), and c-Rel, the {kappa}B1 site bound these factors with higher affinity and functioned more effectively than the {kappa}B2 site in a heterologous promoter. These findings demonstrate that transcriptional control of the KC gene requires cooperation between two {kappa}B sites and is thus distinct from that of the three human GRO genes and the mouse MIP-2 gene. 71 refs., 8 figs.

1. 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

2. 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

3. Subclustering of human immunoglobulin kappa light chain variable region genes

SciTech Connect

Kurth, J.H.; Mountain, J.L.; Cavalli-Sforza, L.L. )

1993-04-01

The human immunoglobulin kappa light chain (IgK) locus includes multiple variable region gene segments (V[sub k]) that can be divided into four subgroups. Oligonucleotide primers were designed to amplify specifically gene segments of the V[sub k]I, V[sub k]II, and V[sub k]III subgroups using the polymerase chain reaction (PCR). Product sequences were subcloned, sequenced, and compared. Phylogenetic analyses of sequences within each subgroup indicate that some subgroups can be subdivided further into [open quotes]sub-subgroups.[close quotes] The history of V[sub k] segment duplications apparently includes at least two separate periods, the first giving rise to the subgroups and the second generating further complexity within each subgroup. Duplications of large pieces of DNA (demonstrated by others through pulsed-field gel electrophoresis) also played a role. Rates of synonymous and nonsynonymous base changes between pairs of sequences suggest that natural selection has played a major role in the evolution of the V[sub k] variable gene segments, leading to sequence conservation in some regions and to increased diversity in others. 34 refs., 4 figs., 3 tabs.

4. Nuclear Factor-kappa B Signaling in Skeletal Muscle Atrophy

PubMed Central

Li, Hong; Malhotra, Shweta; Kumar, Ashok

2008-01-01

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-κB) is one of most important signaling pathways linked to the loss of skeletal muscle mass in various physiological and pathophysiological conditions. Activation of NF-κB 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-κB 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-κB in skeletal muscle with particular reference to different models of muscle-wasting and the development of novel therapy. PMID:18574572

5. 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

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. 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

8. 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.

9. 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.

10. 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.