Sample records for kappa values ranged

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

    Ishikawa, Masamichi; Kitano, Ryota


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

  2. Measurement of Interobserver Disagreement: Correction of Cohen’s Kappa for Negative Values

    Directory of Open Access Journals (Sweden)

    Tarald O. Kvålseth


    Full Text Available As measures of interobserver agreement for both nominal and ordinal categories, Cohen’s kappa coefficients appear to be the most widely used with simple and meaningful interpretations. However, for negative coefficient values when (the probability of observed disagreement exceeds chance-expected disagreement, no fixed lower bounds exist for the kappa coefficients and their interpretations are no longer meaningful and may be entirely misleading. In this paper, alternative measures of disagreement (or negative agreement are proposed as simple corrections or modifications of Cohen’s kappa coefficients. The new coefficients have a fixed lower bound of −1 that can be attained irrespective of the marginal distributions. A coefficient is formulated for the case when the classification categories are nominal and a weighted coefficient is proposed for ordinal categories. Besides coefficients for the overall disagreement across categories, disagreement coefficients for individual categories are presented. Statistical inference procedures are developed and numerical examples are provided.

  3. Poxvirus host range protein CP77 contains an F-box-like domain that is necessary to suppress NF-kappaB activation by tumor necrosis factor alpha but is independent of its host range function. (United States)

    Chang, Shu-Jung; Hsiao, Jye-Chian; Sonnberg, Stephanie; Chiang, Cheng-Ting; Yang, Min-Hsiang; Tzou, Der-Lii; Mercer, Andrew A; Chang, Wen


    Tumor necrosis factor alpha (TNF-alpha) activates the nuclear factor kappaB (NF-kappaB) signaling pathway that regulates expression of many cellular factors playing important roles in innate immune responses and inflammation in infected hosts. Poxviruses employ many strategies to inhibit NF-kappaB activation in cells. In this report, we describe a poxvirus host range protein, CP77, which blocked NF-kappaB activation by TNF-alpha. Immunofluorescence analyses revealed that nuclear translocation of NF-kappaB subunit p65 protein in TNF-alpha-treated HeLa cells was blocked by CP77. CP77 did so without blocking IkappaBalpha phosphorylation, suggesting that upstream kinase activation was not affected by CP77. Using GST pull-down, we showed that CP77 bound to the NF-kappaB subunit p65 through the N-terminal six-ankyrin-repeat region in vitro. CP77 also bound to Cullin-1 and Skp1 of the SCF complex through a C-terminal 13-amino-acid F-box-like sequence. Both regions of CP77 are required to block NF-kappaB activation. We thus propose a model in which poxvirus CP77 suppresses NF-kappaB activation by two interactions: the C-terminal F-box of CP77 binding to the SCF complex and the N-terminal six ankyrins binding to the NF-kappaB subunit p65. In this way, CP77 attenuates innate immune response signaling in cells. Finally, we expressed CP77 or a CP77 F-box deletion protein from a vaccinia virus host range mutant (VV-hr-GFP) and showed that either protein was able to rescue the host range defect, illustrating that the F-box region, which is important for NF-kappaB modulation and binding to SCF complex, is not required for CP77's host range function. Consistently, knocking down the protein level of NF-kappaB did not relieve the growth restriction of VV-hr-GFP in HeLa cells.

  4. Prognostic value of receptor activator of nuclear factor kappa-B (RANK marker in patients with breast cancer

    Directory of Open Access Journals (Sweden)

    S. I. Zabroda


    Full Text Available Despite notable progress made in studying breast cancer (BC, the mechanisms of metastases, in view of the classification into molecular subtypes, in patients with BC remain to be fully uninvestigated, in the presence of a good prognosis in particular. To study novel diagnostic and predictive markers in a new way presents current problems in the pathology of BC. This investigation deals with the expression of osteoprotegerin (OPG in the tumor cells of patients with BC. It enrolled 83 patients with locally advanced BC (T2–4N0–3M0 who had been treated in 2003 to 2010. The inclusion criterion was a histologically verified diagnosis of invasive BC. To study the level of OPG, the investigators conducted an immunohistochemical study of biopsy sections according to the standard protocol. The mean expression of receptor activator of nuclear factor kappa-B (RANK in the BC cells was 18.7 %; itsmedian was 5 % (range, 0–90 %. The patients were divided into 2 groups according to the level of RANK expression: 1 high (higher than the median; 2 low (lower than the median. The high RANK group included 39 patients; the low RANK group comprised 44 patients. Analysis of the clinical and pathological characteristics of BC patients with regard RANK expression did not show any statistically significant differences in the presence or absence of affected regional lymph nodes, T category, and Ki-67 index. The analysis of clinical and pathomorphological and immunohistochemical characteristics in patients with breast cancer, taking into consideration RANK expression level, did not show any statistically significant differences with respect to presence or absence of affected regional lymph nodes, age, T category and Ki-67 index (р > 0.05. However, it revealed the following pattern: the high expression of RANK was more common in patients positive for estrogen and progesterone receptors than in those for negative receptors (p = 0.04.

  5. A Novel "Maximizing Kappa" Approach for Assessing the Ability of a Diagnostic Marker and Its Optimal Cutoff Value. (United States)

    Chang, Chia-Hao; Yang, Jen-Tsung; Lee, Ming-Hsueh


    Threshold-dependent accuracy measures such as true classification rates in ordered multiple-class (k > 3) receiver operating characteristic (ROC) hyper-surfaces have recently been used to assist with medical decision making. However, based on low power performance in some circumstances, we construct a new method that relies on the kappa coefficient to solve such diagnostic problems. Under the approach proposed in the present article, the statistics depend strongly on the [Formula: see text] cutoff threshold, which can be chosen to maximize the kappa statistics of true disease status and of the new biomarker. The Monte Carlo simulation results confirm the effectiveness of the proposed method in terms of its predictive power. The proposed design is then compared with the volume under the ROC hyper-surface by applying it to intracerebral hemorrhagic patients classified into five stroke classes using the National Institutes of Health Stroke Scale.

  6. Normal range values for thromboelastography in healthy adult volunteers. (United States)

    Scarpelini, S; Rhind, S G; Nascimento, B; Tien, H; Shek, P N; Peng, H T; Huang, H; Pinto, R; Speers, V; Reis, M; Rizoli, S B


    Thromboelastography (TEG) provides a functional evaluation of coagulation. It has characteristics of an ideal coagulation test for trauma, but is not frequently used, partially due to lack of both standardized techniques and normal values. We determined normal values for our population, compared them to those of the manufacturer and evaluated the effect of gender, age, blood type, and ethnicity. The technique was standardized using citrated blood, kaolin and was performed on a Haemoscope 5000 device. Volunteers were interviewed and excluded if pregnant, on anticoagulants or having a bleeding disorder. The TEG parameters analyzed were R, K, alpha, MA, LY30, and coagulation index. All volunteers outside the manufacturer's normal range underwent extensive coagulation investigations. Reference ranges for 95% for 118 healthy volunteers were R: 3.8-9.8 min, K: 0.7-3.4 min, alpha: 47.8-77.7 degrees, MA: 49.7-72.7 mm, LY30: -2.3-5.77%, coagulation index: -5.1-3.6. Most values were significantly different from those of the manufacturer, which would have diagnosed coagulopathy in 10 volunteers, for whom additional investigation revealed no disease (81% specificity). Healthy women were significantly more hypercoagulable than men. Aging was not associated with hypercoagulability and East Asian ethnicity was not with hypocoagulability. In our population, the manufacturer's normal values for citrated blood-kaolin had a specificity of 81% and would incorrectly identify 8.5% of the healthy volunteers as coagulopathic. This study supports the manufacturer's recommendation that each institution should determine its own normal values before adopting TEG, a procedure which may be impractical. Consideration should be given to a multi-institutional study to establish wide standard values for TEG.

  7. Nutritive value, for some important range species northern kordofan, sudan

    Directory of Open Access Journals (Sweden)

    Dawelbait E.M


    Full Text Available This study was conducted in North Kordofan State in the year 2009. The objectives were to identify the nutritive value, for the rangelands prevailing in the region .To achieve the objectives field and laboratory works were done. The field work was for sample collection while the lab work include proximate chemical analysis according to (A.O.A.C, 1990, was done for some range plants and trees to identify the nutritional and mineral content. Data were analyzed using SPSS software. The results showed that CP (crude protein, CF (crude fiber, ash, E.E (Ether Extract and NFS (Nitrogen Free Extract were in the range from 6-10, 35-45, 7-10, 1.1-2.1 and 36.7-46.7% respectively. The chemical analysis for selected browse trees were CP5.1%, CF 31-33%, EE 0.4-0.9%, ash 7-8.1% and NFE 53-56.9%. Mineral contents ranged from 0.0144-0.075 ppm for P, 0.002-0.063 ppm for K and 1-2.9 ppm for Iodine. Based on the findings it can be concluded that rangelands of North Kordofan is not poor in the term of nutritive value but it suffers of mineral deficiency. The study recommends that water and dams should be made with optimum distribution to access the non-reachable rangeland because of water deficiency, also supplementary feeding is needed in the term of concentrates and minerals

  8. Hematology and plasma biochemistry reference range values for free-ranging desert tortoises in Arizona. (United States)

    Dickinson, Vanessa M; Jarchow, James L; Trueblood, Mark H


    Baseline values and ranges for 10 hematologic and 32 plasma chemistry parameters were analyzed for 36 free-ranging Sonoran desert tortoises (Gopherus agassizzi) collected in Yavapai and La Paz Counties (Arizona, USA) from 1990 to 1995. Tortoises were radio tagged from 1990 to 1994, and attempts were made to recapture them three times a year. Tortoises were weighed, measured, and chemically immobilized to collect blood for hematology and blood chemistry assessments. Tortoise biochemistry differed (P < 0.01) between sites and sexes and among seasons and years. Normal reference ranges for hematologic and plasma biochemistry parameters were determined. Seasonal and annual differences in hematology and blood chemistry were related to rainfall patterns, forage availability, and physiological condition.

  9. An Automation Interface for Kappa PC

    DEFF Research Database (Denmark)

    Hartvig, Susanne C


    The reports documents an automation interface for Kappa PC. The automation interface can be used to embed Kappa applications in 32-bit Windowsapplications.The interface includes functions for initialising Kappa, for loading an application, for settingvalues, for getting values, and for stopping...

  10. An Automation Interface for Kappa PC

    DEFF Research Database (Denmark)

    Hartvig, Susanne C


    The reports documents an automation interface for Kappa PC. The automation interface can be used to embed Kappa applications in 32-bit Windowsapplications.The interface includes functions for initialising Kappa, for loading an application, for settingvalues, for getting values, and for stopping...

  11. $\\kappa$-Deformations and Extended $\\kappa$-Minkowski Spacetimes

    CERN Document Server

    Borowiec, Andrzej


    We extend our previous study of Hopf-algebraic $\\kappa$-deformations of all inhomogeneous orthogonal Lie algebras ${\\rm iso}(g)$ as written in a tensorial and unified form. Such deformations are determined by a vector $\\tau$ which for Lorentzian signature can be taken time-, light- or space-like. We focus on some mathematical aspects related to this subject. Firstly, we describe real forms with connection to the metric's signatures and their compatibility with the reality condition for the corresponding $\\kappa$-Minkowski (Hopf) module algebras. Secondly, $h$-adic vs $q$-analog (polynomial) versions of deformed algebras including specialization of the formal deformation parameter $\\kappa$ to some numerical value are considered. In the latter the general covariance is lost and one deals with an orthogonal decomposition. The last topic treated in this paper concerns twisted extensions of $\\kappa$-deformations as well as the description of resulting noncommutative spacetime algebras in terms of solvable Lie alge...

  12. Habitat similarity index (HSI) values for greater sage-grouse across their western range. (United States)

    U.S. Geological Survey, Department of the Interior — Habitat similarity index (HSI) values for greater sage-grouse across their western range. HSI values represent the relationship of environmental values at map...

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

    Energy Technology Data Exchange (ETDEWEB)

    Biasi, Glenn; Anderson, John G


    motions analyses used in PSHA, it contributes to the extreme values of peak ground acceleration that the PSHA predicts. Also, in some areas precarious rock evidence indicates that no such accelerations have occurred. 2. The disagreement among analyses in the value of kappa. Previous reports indicate that smallest earthquakes yield kappa estimate 12-20 msec larger than average values from M3 to M4.5 aftershocks of Little Skull Mountain earthquake. 3. The source of kappa. Classically and in engineering usage, kappa is attributed largely to the upper tens or hundreds of meters at the recording site. However, borehole recordings imply that a significant contribution to kappa originates below several hundred meters depth. Also, when earthquakes are considered from a small source region, a true site effect should be common to all recordings. In fact kappa observations of LSM aftershocks to stations on Yucca Mountain and at network stations appear to vary greatly, as though much of kappa actually derives from near the seismic source. 4. The repository overburden contribution to kappa. PSHA estimated ground motions to a free surface at 300 meters depth with properties of confined rock at that depth. Rock mechanical and borehole estimates suggest that several milliseconds of the total kappa accrue between 300 meters to the surface. If estimates of kappa are small at the surface, little is left to reduce incident ground accelerations from the seismic source to the repository level. 5. The variability of kappa. In most cases parametric estimates of kappa have some range of values that fit the data equally well in a statistical sense, so errors in kappa estimates must be addressed. As noted above, kappa at a station also varies significantly for events from the same source area. 6. Are kappa values from small to moderate magnitude earthquakes appropriately applied to the larger, potentially damaging earthquakes of engineering concern? Put another way, is there a significant magnitude

  14. Parallel sort with a ranged, partitioned key-value store in a high perfomance computing environment (United States)

    Bent, John M.; Faibish, Sorin; Grider, Gary; Torres, Aaron; Poole, Stephen W.


    Improved sorting techniques are provided that perform a parallel sort using a ranged, partitioned key-value store in a high performance computing (HPC) environment. A plurality of input data files comprising unsorted key-value data in a partitioned key-value store are sorted. The partitioned key-value store comprises a range server for each of a plurality of ranges. Each input data file has an associated reader thread. Each reader thread reads the unsorted key-value data in the corresponding input data file and performs a local sort of the unsorted key-value data to generate sorted key-value data. A plurality of sorted, ranged subsets of each of the sorted key-value data are generated based on the plurality of ranges. Each sorted, ranged subset corresponds to a given one of the ranges and is provided to one of the range servers corresponding to the range of the sorted, ranged subset. Each range server sorts the received sorted, ranged subsets and provides a sorted range. A plurality of the sorted ranges are concatenated to obtain a globally sorted result.

  15. KAPPA: A Package for Synthesis of optically thin spectra for the non-Maxwellian kappa-distributions based on the CHIANTI database

    CERN Document Server

    Dzifčáková, Elena; Kotrč, Pavel; Fárník, František; Zemanová, Alena


    The non-Maxwellian $\\kappa$-distributions have been detected in the solar transition region and flares. These distributions are characterized by a high-energy tail and a near-Maxwellian core and are known to have significant impact on the resulting optically thin spectra arising from collisionally dominated astrophysical plasmas. We developed the KAPPA package ( for synthesis of such line and continuum spectra. The package is based on the freely available CHIANTI database and software, and can be used in a similar manner. Ionization and recombination rates together with the ionization equilibria are provided for a range of $\\kappa$ values. Distribution-averaged collision strengths for excitation are obtained by an approximate method for all transitions in all ions available within CHIANTI. The validity of this approximate method is tested by comparison with direct calculations. Typical precisions of better than 5% are found, with all cases being within 10%. Tools for calculation of syn...

  16. A quantum inspired model of radar range and range-rate measurements with applications to weak value measurements (United States)

    Escalante, George


    Weak Value Measurements (WVMs) with pre- and post-selected quantum mechanical ensembles were proposed by Aharonov, Albert, and Vaidman in 1988 and have found numerous applications in both theoretical and applied physics. In the field of precision metrology, WVM techniques have been demonstrated and proven valuable as a means to shift, amplify, and detect signals and to make precise measurements of small effects in both quantum and classical systems, including: particle spin, the Spin-Hall effect of light, optical beam deflections, frequency shifts, field gradients, and many others. In principal, WVM amplification techniques are also possible in radar and could be a valuable tool for precision measurements. However, relatively limited research has been done in this area. This article presents a quantum-inspired model of radar range and range-rate measurements of arbitrary strength, including standard and pre- and post-selected measurements. The model is used to extend WVM amplification theory to radar, with the receive filter performing the post-selection role. It is shown that the description of range and range-rate measurements based on the quantum-mechanical measurement model and formalism produces the same results as the conventional approach used in radar based on signal processing and filtering of the reflected signal at the radar receiver. Numerical simulation results using simple point scatterrer configurations are presented, applying the quantum-inspired model of radar range and range-rate measurements that occur in the weak measurement regime. Potential applications and benefits of the quantum inspired approach to radar measurements are presented, including improved range and Doppler measurement resolution.

  17. Bounded sets in the range of an X∗∗-valued measure with bounded variation


    B. Marchena; Piñeiro, C.


    Let X be a Banach space and A⊂X an absolutely convex, closed, and bounded set. We give some sufficient and necessary conditions in order that A lies in the range of a measure valued in the bidual space X∗∗ and having bounded variation. Among other results, we prove that X∗ is a G. T.-space if and only if A lies inside the range of some X∗∗-valued measure with bounded variation whenever XA is isomorphic to a Hilbert space.

  18. Biochemical values in free-ranging white rhinoceros (Ceratotherium simum) in Kruger National Park, South Africa. (United States)

    Mathebula, Nomkhosi; Miller, Michele; Buss, Peter; Joubert, Jennifer; Martin, Laura; Kruger, Marius; Hofmeyr, Markus; Olea-Popelka, Francisco


    Biochemical panels were analyzed on 181 individual free-ranging white rhinoceros (Ceratotherium simum) from Kruger National Park, South Africa. These animals were immobilized between July 2006 and May 2010 for management purposes. Serum and heparinized plasma samples were analyzed using an in-house chemistry analyser (ABAXIS VetScan2). The objectives of this study were to establish biochemical references ranges for Kruger National Park's population of white rhinoceros; to assess differences in values obtained using sera or plasma; and to assess differences in values between gender and different age categories. Significant differences between plasma and serum values were found in most measured parameters except minerals (calcium and magnesium). Because all animals appeared clinically healthy at the time of blood collection, it is hypothesized that choice of anticoagulant may affect certain parameters. Comparison between age categories and gender also resulted in significant differences in a few measured parameters. Identifying differences are important when establishing baseline reference ranges for wildlife populations to allow accurate monitoring of trends that may change over time. The paucity of data on normal biochemical ranges for free-ranging white rhinoceros demonstrates the value of this study and importance of evaluating potential confounding variables.

  19. Limit theory of restricted range approximations of complex-valued continuous functions

    Institute of Scientific and Technical Information of China (English)


    This paper is concerned with the problem of the best restricted range approximations of complex-valued continuous functions. Several properties for the approximating set PΩ such that the classical characterization results and/or the uniqueness results of the best approximations hold are introduced. Under the very mild conditions, we prove that these properties are equivalent that P is a Haar subspce.

  20. Kappa Coefficients for Circular Classifications

    NARCIS (Netherlands)

    Warrens, Matthijs J.; Pratiwi, Bunga C.


    Circular classifications are classification scales with categories that exhibit a certain periodicity. Since linear scales have endpoints, the standard weighted kappas used for linear scales are not appropriate for analyzing agreement between two circular classifications. A family of kappa coefficie

  1. "Dynamic range" of inferred phenotypic HIV drug resistance values in clinical practice.

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    Luke C Swenson

    Full Text Available BACKGROUND: 'Virtual' or inferred phenotypes (vPhenotypes are commonly used to assess resistance to antiretroviral agents in patients failing therapy. In this study, we provide a clinical context for understanding vPhenotype values. METHODS: All HIV-infected persons enrolled in the British Columbia Drug Treatment Program with a baseline plasma viral load (pVL and follow-up genotypic resistance and pVL results were included up to October 29, 2008 (N = 5,277. Change from baseline pVL was determined as a function of Virco vPhenotype, and the "dynamic range" (defined here by the 10th and 90th percentiles for fold-change in IC₅₀ amongst all patients was estimated from the distribution of vPhenotye fold-changes across the cohort. RESULTS: The distribution of vPhenotypes from a large cohort of HIV patients who have failed therapy are presented for all available antiretroviral agents. A maximum change in IC₅₀ of at least 13-fold was observed for all drugs. The dideoxy drugs, tenofovir and most PIs exhibited small "dynamic ranges" with values of 99% of samples. In contrast, zidovudine, lamivudine, emtricitabine and the non-nucleoside reverse transcriptase inihibitors (excluding etravirine had large dynamic ranges. CONCLUSION: We describe the populational distribution of vPhenotypes such that vPhenotype results can be interpreted relative to other patients in a drug-specific manner.

  2. Violations of the 12/23 rule at the mouse immunoglobulin kappa locus, including V kappa-V kappa rearrangement. (United States)

    Vinocur, Jeffrey M; Fesnak, Andrew D; Liu, Yang; Charan, Deepshikha; Prak, Eline T Luning


    Classically, recombination between immunoglobulin gene segments uses a pair of recombination signal sequences (RSSs) with dissimilar spacers (the "12/23 rule"). Using a series of different genotyping assays, four different kinds of atypical rearrangements were identified at the murine kappa locus: (1) V kappa to V kappa, (2) J kappa to J kappa, (3) V kappa to iRS, a heptameric sequence found in the J kappa C kappa intron, and (4) a possible by-product of a rearrangement between a V kappa and the hypothetical 12-RSS side of a pre-existing signal joint. The novel V kappa-V kappa structure prompted further characterization. Sequence analysis of 14 different V kappa-V kappa rearrangements cloned from murine splenocytes and hybridomas revealed a V kappa 4 family member as one participant in 13 rearrangements, but no rearrangements contained two V kappa 4 genes. The V kappa 4 partner in the V kappa-V kappa rearrangement exhibited more trimming of nucleotides at the V kappa-V kappa junction. A signal joint derived from the inversional rearrangement of two neighboring V kappas was also recovered. These data suggest that the V kappa-V kappa structures arise via RAG-mediated, intrachromosomal recombination.


    Energy Technology Data Exchange (ETDEWEB)

    Kaplan, D


    Performance assessments (PAs) are risk calculations used to estimate the amount of low-level radioactive waste that can be disposed at DOE sites. Distribution coefficients (K{sub d} values) are input parameters used in PA calculations to provide a measure of radionuclide sorption to sediment; the greater the K{sub d} value, the greater the sorption and the slower the estimated movement of the radionuclide through sediment. Understanding and quantifying K{sub d} value variability is important for estimating the uncertainty of PA calculations. Without this information, it is necessary to make overly conservative estimates about the possible limits of K{sub d} values, which in turn may increase disposal costs. Finally, technetium is commonly found to be amongst the radionuclides posing potential risk at waste disposal locations because it is believed to be highly mobile in its anionic form (pertechnetate, TcO{sub 4}{sup -}), it exists in relatively high concentrations in SRS waste, and it has a long half-life (213,000 years). The objectives of this laboratory study were to determine under SRS environmental conditions: (1) whether and to what extent TcO{sub 4}{sup -} sorbs to sediments, (2) the range of Tc K{sub d} values, (3) the distribution (normal or log-normal) of Tc K{sub d} values, and (4) how strongly Tc sorbs to SRS sediments through desorption experiments. Objective 3, to identify the Tc K{sub d} distribution is important because it provides a statistical description that influences stochastic modeling of estimated risk. The approach taken was to collect 26 sediments from a non-radioactive containing sediment core collected from E-Area, measure Tc K{sub d} values and then perform statistical analysis to describe the measured Tc K{sub d} values. The mean K{sub d} value was 3.4 {+-} 0.5 mL/g and ranged from -2.9 to 11.2 mL/g. The data did not have a Normal distribution (as defined by the Shapiro-Wilk's Statistic) and had a 95-percentile range of 2.4 to 4

  4. Emotion rendering in music: range and characteristic values of seven musical variables. (United States)

    Bresin, Roberto; Friberg, Anders


    Many studies on the synthesis of emotional expression in music performance have focused on the effect of individual performance variables on perceived emotional quality by making a systematical variation of variables. However, most of the studies have used a predetermined small number of levels for each variable, and the selection of these levels has often been done arbitrarily. The main aim of this research work is to improve upon existing methodologies by taking a synthesis approach. In a production experiment, 20 performers were asked to manipulate values of 7 musical variables simultaneously (tempo, sound level, articulation, phrasing, register, timbre, and attack speed) for communicating 5 different emotional expressions (neutral, happy, scary, peaceful, sad) for each of 4 scores. The scores were compositions communicating four different emotions (happiness, sadness, fear, calmness). Emotional expressions and music scores were presented in combination and in random order for each performer for a total of 5 × 4 stimuli. The experiment allowed for a systematic investigation of the interaction between emotion of each score and intended expressed emotions by performers. A two-way analysis of variance (ANOVA), repeated measures, with factors emotion and score was conducted on the participants' values separately for each of the seven musical factors. There are two main results. The first one is that musical variables were manipulated in the same direction as reported in previous research on emotional expressive music performance. The second one is the identification for each of the five emotions the mean values and ranges of the five musical variables tempo, sound level, articulation, register, and instrument. These values resulted to be independent from the particular score and its emotion. The results presented in this study therefore allow for both the design and control of emotionally expressive computerized musical stimuli that are more ecologically valid than

  5. Skill and relative economic value of medium-range hydrological ensemble predictions

    Directory of Open Access Journals (Sweden)

    E. Roulin


    Full Text Available A hydrological ensemble prediction system, integrating a water balance model with ensemble precipitation forecasts from the European Centre for Medium-Range Weather Forecasts (ECMWF Ensemble Prediction System (EPS, is evaluated for two Belgian catchments using verification methods borrowed from meteorology. The skill of the probability forecast that the streamflow exceeds a given level is measured with the Brier Skill Score. Then the value of the system is assessed using a cost-loss decision model. The verification results of the hydrological ensemble predictions are compared with the corresponding results obtained for simpler alternatives as the one obtained by using of the deterministic forecast of ECMWF which is characterized by a higher spatial resolution or by using of the EPS ensemble mean.

  6. Serum protein electrophoresis values for free-ranging and zoo-based koalas (Phascolarctos cinereus). (United States)

    Pye, Geoffrey W; Ellis, William; Fitzgibbon, Sean; Opitz, Brian; Keener, Laura; Arheart, Kristopher L; Cray, Carolyn


    In a clinical setting, especially with species of special interest, it is important to use all clinical pathology testing options for general health monitoring and diagnosis. Protein electrophoresis (EPH) has previously been shown to be an important adjunct tool in veterinary medicine. Serum samples from 18 free-ranging and 12 zoo-based koalas (Phascolarctos cinereus) were subject to EPH analysis. Significant differences were found between the two groups for the following values: total protein, albumin, beta globulins, and albumin-globulin ratio (P < 0.05). By using the combined data, the minimum-maximum values for the EPH fractions were as follows: total protein 5.0-7.8 g/dl, albumin 2.8-4.7 g/dl, alpha-1 globulins 0.5-1.1 g/dl, alpha-2 globulins 0.3-0.7 g/dl, beta globulins 0.4-1.0 g/dl, gamma globulins 0.2-1.0 g/dl, and albumin-globulin ratio 1.0-2.1.

  7. Intracerebroventricular administration of kappa-agonists induces convulsions in mice. (United States)

    Bansinath, M; Ramabadran, K; Turndorf, H; Shukla, V K


    Intracerebroventricular (ICV) administration of kappa-agonists (PD 117302, U-50488H and U-69593) induced convulsions in a dose-related manner in mice. The dose at which 50% of animals convulsed (CD50) was in nmol ranges for all opioids. Among the opioids used, PD 117302 was the most potent convulsant. ICV administration of either vehicle alone or U-53445E, a non-kappa-opioid (+) enantiomer of U-50488H did not induce convulsions. The convulsive response of kappa-agonists was differentially susceptible for antagonism by naloxone and/or MR 2266. Collectively, these findings support the view that convulsions induced by kappa-agonists in mice involve stereospecific opioid receptor mechanisms. Furthermore, the convulsant effect of kappa-agonists could not be modified by pretreatment with MK-801, ketamine, muscimol or baclofen. It is concluded that kappa-opioid but not NMDA or GABA receptor mechanisms are involved in convulsions induced by kappa-agonists. These results are the first experimental evidence implicating stereospecific kappa-receptor mechanisms in opioid-induced convulsions in mice.

  8. The value of DNA paternity identification in beef cattle: examples from Nevada's free-range ranches. (United States)

    Gomez-Raya, L; Priest, K; Rauw, W M; Okomo-Adhiambo, M; Thain, D; Bruce, B; Rink, A; Torell, R; Grellman, L; Narayanan, R; Beattie, C W


    The feasibility and economic value of DNA paternity identification were investigated and illustrated using Nevada beef cattle operations. A panel of 15 microsatellites was genotyped in 2,196 animals from 8 ranches with a total of 31,571 genotypes. Probabilities of exclusion for each marker within ranch and across ranches were computed. Joint probabilities of exclusion for the 15 microsatellites were also determined, resulting in values over 0.99 for any individual ranch and across ranches. Dropping 1 or 2 microsatellites with the lowest probabilities of exclusion resulted in joint probabilities greater than 0.99 and with marginal reduction compared with the probabilities with 15 microsatellites. Formulas for benefit-cost analysis for a DNA paternity identification program in beef cattle were derived. Genotyping 15 microsatellites with 20 calves per sire resulted in benefits of $1.71 and $2.44 per dollar invested at bull culling rates of 0.20 and 0.30, respectively. The breakpoints for the program to be profitable occurred when the ratio of the price of 1 kg of calf liveweight over the cost of genotyping 1 microsatellite was greater than 1.1 for a bull culling rate of 0.30. Benefit-cost analysis was also derived under incomplete DNA paternity identification using a lower number of DNA markers than necessary to achieve joint probabilities of exclusion of 0.99. Approximately a 20% increase in the benefit-cost ratio was achieved using 10 vs. 12 microsatellites with incomplete paternity identification. The greater the number of bulls in the operation, the lower the benefit-cost ratio of the paternity testing program. Low probabilities of exclusion and a high number of bulls in the beef operation reduced the benefit-cost ratio dramatically. The DNA paternity identification programs are feasible and may be profitable for free-range beef cattle operations.

  9. Haematological and serum biochemical reference values in free-ranging red deer (Cervus elaphus atlanticus

    Directory of Open Access Journals (Sweden)

    Olav Rosef


    Full Text Available Analyses of haematological and biochemical constituents were carried out on the Norwegian subspecies of free-ranging red deer (Cervus elaphus atlanticus. All animals were captured from January to March by using a mixture of xylazine and tiletamin-zolazepam. Immobilisation was performed with plastic projectile syringes fired from a dart gun. Fourteen haematological parameters were analysed. There were no differences in the values between hinds and stags and between adults and calves (P > 0.01. Of the 22 biochemical compounds investigated there was a significant difference (P < 0.01 between calves and adults for lactate dehydrogenase (LD, globulin, beta globulin, gamma globulin, and the minerals Na, K, Mg, Zn, Ca, and P. Differences (P < 0.01 between hinds and stags were found in cholesterol, gamma glutamyl transferase (GGT, alpha-1 globulin, alpha-2 globulin and Cu. The blood values determined in this study can be used as reference values for this red deer subspecies immobilised with a mixture of xylazine-tiletamin-zolazepam for health control and diagnosis of diseases.Abstract in Norwegian /Sammendrag:Hematologiske og biokjemiske parametere er analysert på norsk frittlevende hjort (Cervus elaphus atlanticus. Hjorten ble immobilisert i tidsrommet januar til mars ved hjelp av et spesialgevær ladet med plast kanyler som inneholdt en blanding av xylazin og tiletamin-zolazepam. Det var ingen forskjeller i de14 undersøkte hematologiske verdiene mellom hinder, kalver og bukker (P>0,01. Av de 22 biokjemiske parametrene som ble undersøkt var det en signifikant forskjell mellom kalver og voksne (P<0,01 når det gjelder laktat dehydrogenase, globulin, beta globulin, gamma globulin og mineralene Na, K, Mg, Zn, Ca og P. Det var en signifikant forskjell mellom hinder og bukker (P<0.01 på parametrene kolesterol, gamma glutamyl transferase, alfa-1 globulin, alfa-2 globulin og Cu. Blodverdiene som ble målt i dette studiet kan bli brukt som referanseverdier

  10. Measurements of the Sensitivity of Aerosol Hygroscopicity and the kappa Parameter to the O/C Ratio


    Rickards, Andrew M J; Miles, Rachael E. H.; Davies, James F.; Marshall, Frances H.; Reid, Jonathan P.


    We report measurements of the subsaturated hygroscopic growth of aerosol particles composed of single organic components of varying oxygen-to-carbon ratio up to relative humidities approaching saturation using the techniques of aerosol optical tweezers and an electrodynamic balance. The variation in the hygroscopicity parameter kappa between compounds of even the same O/C ratio is found to be significant with, for example, a range in kappa values from 0.12 to 0.38 for compounds with an O/C of...

  11. Assessing the umbrella value of a range-wide conservation network for jaguars (Panthera onca). (United States)

    Thornton, Daniel; Zeller, Kathy; Rondinini, Carlo; Boitani, Luigi; Crooks, Kevin; Burdeh, Christopher; Rabinowitz, Alan; Quigley, Howard


    Umbrella species are employed as conservation short-cuts for the design of reserves or reserve networks. However, empirical data on the effectiveness of umbrellas is equivocal, which has prevented more widespread application of this conservation strategy. We perform a novel, large-scale evaluation of umbrella species by assessing the potential umbrella value of a jaguar (Panthera onca) conservation network (consisting of viable populations and corridors) that extends from Mexico to Argentina. Using species richness, habitat quality, and fragmentation indices of ~1500 co-occurring mammal species, we show that jaguar populations and corridors overlap a substantial amount and percentage of high-quality habitat for co-occurring mammals and that the jaguar network performs better than random networks in protecting high-quality, interior habitat. Significantly, the effectiveness of the jaguar network as an umbrella would not have been noticeable had we focused on species richness as our sole metric of umbrella utility. Substantial inter-order variability existed, indicating the need for complementary conservation strategies for certain groups of mammals. We offer several reasons for the positive result we document, including the large spatial scale of our analysis and our focus on multiple metrics of umbrella effectiveness. Taken together, our results demonstrate that a regional, single-species conservation strategy can serve as an effective umbrella for the larger community and should help conserve viable populations and connectivity for a suite of co-occurring mammals. Current and future range-wide planning exercises for other large predators may therefore have important umbrella benefits.

  12. Losing your edge: climate change and the conservation value of range-edge populations. (United States)

    Rehm, Evan M; Olivas, Paulo; Stroud, James; Feeley, Kenneth J


    Populations occurring at species' range edges can be locally adapted to unique environmental conditions. From a species' perspective, range-edge environments generally have higher severity and frequency of extreme climatic events relative to the range core. Under future climates, extreme climatic events are predicted to become increasingly important in defining species' distributions. Therefore, range-edge genotypes that are better adapted to extreme climates relative to core populations may be essential to species' persistence during periods of rapid climate change. We use relatively simple conceptual models to highlight the importance of locally adapted range-edge populations (leading and trailing edges) for determining the ability of species to persist under future climates. Using trees as an example, we show how locally adapted populations at species' range edges may expand under future climate change and become more common relative to range-core populations. We also highlight how large-scale habitat destruction occurring in some geographic areas where many species range edge converge, such as biome boundaries and ecotones (e.g., the arc of deforestation along the rainforest-cerrado ecotone in the southern Amazonia), can have major implications for global biodiversity. As climate changes, range-edge populations will play key roles in helping species to maintain or expand their geographic distributions. The loss of these locally adapted range-edge populations through anthropogenic disturbance is therefore hypothesized to reduce the ability of species to persist in the face of rapid future climate change.

  13. In-situ observation of electron kappa distributions associated with discrete auroral arcs (United States)

    Ogasawara, Keiichi; Livadiotis, George; Samara, Marilia; Michell, Robert; Grubbs, Guy


    The Medium-energy Electron SPectrometer (MESP) sensor aboard a NASA sounding rocket was launched from Poker Flat Research Range on 3 March 2014 as a part of Ground-to-Rocket Electrodynamics-Electrons Correlative Experiment (GREECE) mission. GREECE targeted to discover convergent E-field structures at low altitude ionosphere to find their contribution to the rapid fluid-like structures of aurora, and MESP successfully measured the precipitating electrons from 2 to 200 keV within multiple discrete auroral arcs with the apogee of 350 km. MESP's unprecedented electron energy acceptance and high geometric factor made it possible to investigate precise populations of the suprathermal components measured in the inverted-V type electron energy distributions. The feature of these suprathermal electrons are explained by the kappa distribution functions with the parameters (densty, temperature, and kappa) consistent with the near-Earth tail plasma sheet, suggesting the source population of the auroral electrons. The kappa-values are different between each arc observed as a function of latitude, but are almost stable within one discrete arc. We suggest that this transition of kappa reflects the probagation history of source electrons through the plasma sheet by changing its state from non-equilibrium electron distributions to thermal ones.

  14. Curie law for systems described by kappa distributions (United States)

    Livadiotis, George


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

  15. Forecasting Value-at-Risk Using Nonlinear Regression Quantiles and the Intraday Range

    NARCIS (Netherlands)

    C.W.S. Chen (Cathy); R. Gerlach (Richard); B.B.K. Hwang (Bruce); M.J. McAleer (Michael)


    textabstractValue-at-Risk (VaR) is commonly used for financial risk measurement. It has recently become even more important, especially during the 2008-09 global financial crisis. We propose some novel nonlinear threshold conditional autoregressive VaR (CAViar) models that incorporate intra-day pric

  16. An extended set-value observer for position estimation using single range measurements

    DEFF Research Database (Denmark)

    Marcal, Jose; Jouffroy, Jerome; Fossen, Thor I.

    of transponders. The knowledge of the bearing of the vehicle and the range measurements from a single location can provide a solution which is sensitive to the trajectory that the vehicle is following, since there is no complete constraint on the position estimate with a single beacon. In this paper...

  17. An extended set-value observer for position estimation using single range measurements

    DEFF Research Database (Denmark)

    Marcal, Jose; Jouffroy, Jerome; Fossen, Thor I.

    of transponders. The knowledge of the bearing of the vehicle and the range measurements from a single location can provide a solution which is sensitive to the trajectory that the vehicle is following, since there is no complete constraint on the position estimate with a single beacon. In this paper...

  18. Electromagnetic ion-cyclotron instability in a dusty plasma with product-bi-kappa distributions for the plasma particles (United States)

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


    We study the dispersion relation for parallel propagating ion-cyclotron (IC) waves in a dusty plasma, considering situations where the velocity dispersion along perpendicular direction is greater than along the parallel direction, and considering the use of product-bi-kappa (PBK) velocity distributions for the plasma particles. The results obtained by numerical solution of the dispersion relation, in a case with isotropic Maxwellian distributions for electrons and PBK distribution for ions, show the occurrence of the electromagnetic ion-cyclotron instability (EMIC), and show that the decrease in the kappa indexes of the PBK ion distribution leads to significant increase in the magnitude of the growth rates and in the range of wavenumber for which the instability occurs. On the other hand, for anisotropic Maxwellian distribution for ions and PBK distribution for electrons, the decrease of the kappa index in the PBK electron distribution contributes to reduce the growth rate of the EMIC instability, but the reduction effect is less pronounced than the increase obtained with ion PBK distribution with the same kappa index. The results obtained also show that, as a general rule, the presence of a dust population contributes to reduce the instability in magnitude of the growth rates and range, but that in the case of PBK ion distribution with small kappa indexes the instability may continue to occur for dust populations which would eliminate completely the instability in the case of bi-Maxwellian ion distributions. It has also been seen that the anisotropy due to the kappa indexes in the ion PBK distribution is not so efficient in producing the EMIC instability as the ratio of perpendicular and parallel ion temperatures, for equivalent value of the effective temperature.

  19. Plasma Dispersion Function for the Kappa Distribution (United States)

    Podesta, John J.


    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. Blood optical properties at various glucose level values in THz frequency range (United States)

    Gusev, S. I.; Borovkova, M. A.; Strepitov, M. A.; Khodzitsky, M. K.


    the patients. Most biomolecules have characteristic signature frequencies in the terahertz (THz) range, which can reveal their presence and determine the concentration. Therefore, this paper is intended to study the blood optical properties in the THz frequency range in order to determine THz radiation effect on blood. The main aim of this investigation is to determine the effect of blood glucose concentration on the blood optical properties. In the case if blood optical properties vary at different glucose concentrations having a proportional relationship between them, these results will confirm the possibility of development of non-invasive procedures for blood glucose level diagnostics.

  1. Electroacoustic theory for concentrated colloids with overlapped DLs at arbitrary kappa alpha. I. Application to nanocolloids and nonaqueous colloids. (United States)

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


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

  2. Interactions among oscillatory pathways in NF-kappa B signaling

    Directory of Open Access Journals (Sweden)

    White Michael RH


    Full Text Available Abstract Background Sustained stimulation with tumour necrosis factor alpha (TNF-alpha induces substantial oscillations—observed at both the single cell and population levels—in the nuclear factor kappa B (NF-kappa B system. Although the mechanism has not yet been elucidated fully, a core system has been identified consisting of a negative feedback loop involving NF-kappa B (RelA:p50 hetero-dimer and its inhibitor I-kappa B-alpha. Many authors have suggested that this core oscillator should couple to other oscillatory pathways. Results First we analyse single-cell data from experiments in which the NF-kappa B system is forced by short trains of strong pulses of TNF-alpha. Power spectra of the ratio of nuclear-to-cytoplasmic concentration of NF-kappa B suggest that the cells' responses are entrained by the pulsing frequency. Using a recent model of the NF-kappa B system due to Caroline Horton, we carried out extensive numerical simulations to analyze the response frequencies induced by trains of pulses of TNF-alpha stimulation having a wide range of frequencies and amplitudes. These studies suggest that for sufficiently weak stimulation, various nonlinear resonances should be observable. To explore further the possibility of probing alternative feedback mechanisms, we also coupled the model to sinusoidal signals with a wide range of strengths and frequencies. Our results show that, at least in simulation, frequencies other than those of the forcing and the main NF-kappa B oscillator can be excited via sub- and superharmonic resonance, producing quasiperiodic and even chaotic dynamics. Conclusions Our numerical results suggest that the entrainment phenomena observed in pulse-stimulated experiments is a consequence of the high intensity of the stimulation. Computational studies based on current models suggest that resonant interactions between periodic pulsatile forcing and the system's natural frequencies may become evident for sufficiently

  3. Numerical solution of High-kappa model of superconductivity

    Energy Technology Data Exchange (ETDEWEB)

    Karamikhova, R. [Univ. of Texas, Arlington, TX (United States)


    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.

  4. Electron acoustic solitary waves with kappa-distributed electrons

    Energy Technology Data Exchange (ETDEWEB)

    Devanandhan, S; Singh, S V; Lakhina, G S, E-mail: [Indian Institute of Geomagnetism, New Panvel (West), Navi Mumbai (India)


    Electron acoustic solitary waves are studied in a three-component, unmagnetized plasma composed of hot electrons, fluid cold electrons and ions having finite temperatures. Hot electrons are assumed to have kappa distribution. The Sagdeev pseudo-potential technique is used to study the arbitrary amplitude electron-acoustic solitary waves. It is found that inclusion of cold electron temperature shrinks the existence regime of the solitons, and soliton electric field amplitude decreases with an increase in cold electron temperature. A decrease in spectral index, {kappa}, i.e. an increase in the superthermal component of hot electrons, leads to a decrease in soliton electric field amplitude as well as the soliton velocity range. The soliton solutions do not exist beyond T{sub c}/T{sub h}>0.13 for {kappa}=3.0 and Mach number M=0.9 for the dayside auroral region parameters.

  5. Anomalous skin effects in anisotropic kappa distributed plasmas (United States)

    Khokhar, Tajammal H.; Bashir, M. F.; Murtaza, G.


    Anomalous skin effects (ASEs) are studied for the transverse electromagnetic waves in an unmagnetized collisionless plasma using anisotropic kappa distribution. The effects of the kappa spectral index (κ), temperature anisotropy ( A =T⊥/T||) , and the wave frequency (ω) on the ASEs are highlighted to be applicable for a wide range of plasma parameters. It is shown that the skin depth is reduced in a kappa distributed plasma as compared to the Maxwellian one. The anisotropy may enhance/reduce the skin depth depending upon the wave frequency to plasma frequency ratio ( ω/ωp ) and the regime of the anisotropy (i.e., A > 1 or A < 1). The results for the Maxwellian distribution ( κ→∞ ) are also retrieved. The possible applications to space and laboratory plasmas are also discussed.

  6. Non-Cooperative Target Recognition by Means of Singular Value Decomposition Applied to Radar High Resolution Range Profiles

    Directory of Open Access Journals (Sweden)

    Patricia López-Rodríguez


    Full Text Available Radar high resolution range profiles are widely used among the target recognition community for the detection and identification of flying targets. In this paper, singular value decomposition is applied to extract the relevant information and to model each aircraft as a subspace. The identification algorithm is based on angle between subspaces and takes place in a transformed domain. In order to have a wide database of radar signatures and evaluate the performance, simulated range profiles are used as the recognition database while the test samples comprise data of actual range profiles collected in a measurement campaign. Thanks to the modeling of aircraft as subspaces only the valuable information of each target is used in the recognition process. Thus, one of the main advantages of using singular value decomposition, is that it helps to overcome the notable dissimilarities found in the shape and signal-to-noise ratio between actual and simulated profiles due to their difference in nature. Despite these differences, the recognition rates obtained with the algorithm are quite promising.

  7. Single-cell NF-kappaB dynamics reveal digital activation and analogue information processing. (United States)

    Tay, Savaş; Hughey, Jacob J; Lee, Timothy K; Lipniacki, Tomasz; Quake, Stephen R; Covert, Markus W


    Cells operate in dynamic environments using extraordinary communication capabilities that emerge from the interactions of genetic circuitry. The mammalian immune response is a striking example of the coordination of different cell types. Cell-to-cell communication is primarily mediated by signalling molecules that form spatiotemporal concentration gradients, requiring cells to respond to a wide range of signal intensities. Here we use high-throughput microfluidic cell culture and fluorescence microscopy, quantitative gene expression analysis and mathematical modelling to investigate how single mammalian cells respond to different concentrations of the signalling molecule tumour-necrosis factor (TNF)-alpha, and relay information to the gene expression programs by means of the transcription factor nuclear factor (NF)-kappaB. We measured NF-kappaB activity in thousands of live cells under TNF-alpha doses covering four orders of magnitude. We find, in contrast to population-level studies with bulk assays, that the activation is heterogeneous and is a digital process at the single-cell level with fewer cells responding at lower doses. Cells also encode a subtle set of analogue parameters to modulate the outcome; these parameters include NF-kappaB peak intensity, response time and number of oscillations. We developed a stochastic mathematical model that reproduces both the digital and analogue dynamics as well as most gene expression profiles at all measured conditions, constituting a broadly applicable model for TNF-alpha-induced NF-kappaB signalling in various types of cells. These results highlight the value of high-throughput quantitative measurements with single-cell resolution in understanding how biological systems operate.

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

    Energy Technology Data Exchange (ETDEWEB)

    Santos, M. S. dos; Ziebell, L. F., E-mail:; Gaelzer, R., E-mail: [Instituto de Física, Universidade Federal do Rio Grande do Sul, Caixa Postal 15051, CEP: 91501-970 Porto Alegre, RS (Brazil)


    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.

  9. Determination of the exact range of the value of the parameter corresponding to chaos based on the Silnikov criterion (United States)

    Li, Wei-Yi; Zhang, Qi-Chang; Wang, Wei


    Based on the Silnikov criterion, this paper studies a chaotic system of cubic polynomial ordinary differential equations in three dimensions. Using the Cardano formula, it obtains the exact range of the value of the parameter corresponding to chaos by means of the centre manifold theory and the method of multiple scales combined with Floque theory. By calculating the manifold near the equilibrium point, the series expression of the homoclinic orbit is also obtained. The space trajectory and Lyapunov exponent are investigated via numerical simulation, which shows that there is a route to chaos through period-doubling bifurcation and that chaotic attractors exist in the system. The results obtained here mean that chaos occurred in the exact range given in this paper. Numerical simulations also verify the analytical results.

  10. Hawking radiation in the kappa-spacetime

    CERN Document Server

    Harikumar, E


    In this paper, we analyze the Hawking radiation of kappa-deformed Schwarzchild black hole and obtain the deformed Hawking temperature. For this, we first derive deformed metric for the kappa-spacetime, which in the generic case, is not a symmetric tensor and also has a momentum dependence. We show that the Schwarzchild metric obtained in the kappa-deformed spacetime has a dependence on energy. We use the fact that the deformed metric is conformally flat in the 1+1 dimensions, to solve the kappa-deformed Klein-Gordon equation in the background of the Schwarzchild metric. The method of Boguliobov coefficients is then used to calculate the thermal spectrum of kappa-deformed-Schwarzchild black hole and show that the Hawking temperature is modified by the non-commutativity of the kappa-spacetime.

  11. Oncogenic activation of NF-kappaB. (United States)

    Staudt, Louis M


    Recent genetic evidence has established a pathogenetic role for NF-kappaB signaling in cancer. NF-kappaB signaling is engaged transiently when normal B lymphocytes respond to antigens, but lymphomas derived from these cells accumulate genetic lesions that constitutively activate NF-kappaB signaling. Many genetic aberrations in lymphomas alter CARD11, MALT1, or BCL10, which constitute a signaling complex that is intermediate between the B-cell receptor and IkappaB kinase. The activated B-cell-like subtype of diffuse large B-cell lymphoma activates NF-kappaB by a variety of mechanisms including oncogenic mutations in CARD11 and a chronic active form of B-cell receptor signaling. Normal plasma cells activate NF-kappaB in response to ligands in the bone marrow microenvironment, but their malignant counterpart, multiple myeloma, sustains a variety of genetic hits that stabilize the kinase NIK, leading to constitutive activation of the classical and alternative NF-kappaB pathways. Various oncogenic abnormalities in epithelial cancers, including mutant K-ras, engage unconventional IkappaB kinases to activate NF-kappaB. Inhibition of constitutive NF-kappaB signaling in each of these cancer types induces apoptosis, providing a rationale for the development of NF-kappaB pathway inhibitors for the treatment of cancer.

  12. Observer variability in the assessment of type and dysplasia of colorectal adenomas, analyzed using kappa statistics

    DEFF Research Database (Denmark)

    Jensen, P; Krogsgaard, M R; Christiansen, J


    of adenomas were assessed twice by three experienced pathologists, with an interval of two months. Results were analyzed using kappa statistics. RESULTS: For agreement between first and second assessment (both type and grade of dysplasia), kappa values for the three specialists were 0.5345, 0.9022, and 0....... The kappa values for Observer A vs. B and Observer C vs. B were 0.3480 and 0.3770, respectively (both type and dysplasia). Values for type were better than for dysplasia, but agreement was only fair to moderate. CONCLUSION: The interobserver agreement was moderate to almost perfect, but the intraobserver...... agreement was only fair to moderate. A simpler classification system or a centralization of assessments would probably increase kappa values....

  13. Prospective Study of a Cohort of Russian Nijmegen Breakage Syndrome Patients Demonstrating Predictive Value of Low Kappa-Deleting Recombination Excision Circle (KREC Numbers and Beneficial Effect of Hematopoietic Stem Cell Transplantation (HSCT

    Directory of Open Access Journals (Sweden)

    Elena Deripapa


    Full Text Available BackgroundNijmegen breakage syndrome (NBS is a combined primary immunodeficiency with DNA repair defect, microcephaly, and other phenotypical features. It predominantly occurs in Slavic populations that have a high frequency of carriers with the causative NBN gene c.657_661del5 mutation. Due to the rarity of the disease in the rest of the world, studies of NBS patients are few. Here, we report a prospective study of a cohort of Russian NBS patients.Methods35 Russian NBS patients of ages 1–19 years, referred to our Center between years 2012 and 2016, were prospectively studied.ResultsDespite the fact that in 80% of the patients microcephaly was diagnosed at birth or shortly thereafter, the average delay of NBS diagnosis was 6.5 years. Though 80% of the patients had laboratory signs of immunodeficiency, only 51% of the patients experienced significant infections. Autoimmune complications including interstitial lymphocytic lung disease and skin granulomas were noted in 34%, malignancies—in 57% of the patients. T-cell excision circle (TREC/kappa-deleting recombination excision circle (KREC levels were low in the majority of patients studied. Lower KREC levels correlated with autoimmune and oncological complications. Fifteen patients underwent hematopoietic stem cell transplantation (HSCT, 10 of them were alive and well, with good graft function. Three patients in the HSCT group and five non-transplanted patients died; tumor progression being the main cause of death. The probability of the overall survival since NBS diagnosis was 0.76 in the HSCT group and 0.3 in the non-transplanted group.ConclusionBased on our findings of low TRECs in most NBS patients, independent of their age, TREC detection can be potentially useful for detection of NBS patients during neonatal screening. KREC concentration can be used as a prognostic marker of disease severity. HSCT is a viable treatment option in NBS and should be especially considered in patients with

  14. Crocodylian nuclear factor kappa B. (United States)

    Merchant, Mark; Morkotinis, Vasileios; Hale, Amber; White, Mary; Moran, Chris


    We deduced the amino acid (aa) sequence of the nuclear factor kappa B (NFκB) protein from genomic data for the American alligator (Alligator mississippiensis), the estuarine crocodile (Crocodylus porosus), and the Indian gharial (Gavialis gangeticus). A 105kDa protein, NFκB1 exhibits complex post-translational processing, multiple mechanisms of activation, and acts as precursor for a p50, a Rel homology transcription factor which influences the expression of key genes for developmental processes, apoptosis, and immune function. The aa sequences of the crocodylian proteins share very high identity with each other (97.2±0.7%), birds (81.0±1.1%, n=6), mammals (75.3±1.6%, n=4), reptiles (80.3±5.1%, n=2), and less identity with fish (55.5±5.5%, n=4) and one amphibian (66.1±0.8%). The crocodylian protein has a well-conserved Rel homology domain, a nuclear localization signal, and a glycine-rich region which facilitates proteasome-mediated generation of p50. The Rel homology domain contains sequences responsible for dimerization, DNA-binding, and nuclear translocation. In addition, seven ankyrin repeats were located, which putatively allow for inhibition of transcriptional regulation by mediating interaction with Inhibitor kappa B. Other features include a death domain, and conserved serine residues, near the C-terminal end, which act as potential phosphorylation sites for activation of the proteolytic generation of p50. Western blot analysis showed both the 105kDa precursor and the 50kDa mature NFκB were expressed in the alligator liver. Nuclear factor κB exhibited diffuse cytoplasmic distribution in alligator hepatocytes, and almost no cytoplasmic localization in infected animals. In addition, nuclear NFκB exhibited specific binding to the consensus NFκB promoter element. Published by Elsevier Inc.

  15. 3D Maxwell-Vlasov boundary value problem solution in stellarator geometry in ion cyclotron frequency range. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Vdovin, V.; Watari, T.; Fukuyama, A.


    We develop the theory for the wave excitation, propagation and absorption in 3-dimensional (3D) stellarator equilibrium high beta plasma in ion cyclotron frequency range (ICRF). This theory forms a basis for a 3D code creation, urgently needed for the ICRF heating scenarios development for the constructed LHD and projected W7-X stellarators and for the stellarators being at operation (like CHS, W7-AS, etc.). The theory solves the 3D Maxwell-Vlasov antenna-plasma-conducting shell boundary value problem in the non - orthogonal flux coordinates ({psi}, {theta}, {phi}), {psi} being magnetic flux function, {theta} and {phi} being the poloidal and toroidal angles, respectively. All basic physics, like wave refraction, reflection and diffraction are firstly self consistently included, along with the fundamental ion and ion minority cyclotron resonances, two ion hybrid resonance, electron Landau and TTMP absorption. Antenna reactive impedance and loading resistance are also calculated and urgently needed for an antenna -generator matching. This is accomplished in a real confining magnetic field being varying in a plasma major radius direction, in toroidal and poloidal directions, through making use of the hot dense plasma dielectric kinetic tensor. The theory is developed in a manner that includes tokamaks and magnetic mirrors as the particular cases through general metric tensor (provided by an equilibrium solver) treatment of the wave equations. We describe the structure of newly developed stellarator ICRF 3D full wave code STELION, based on theory described in this report. (J.P.N.)

  16. NMR analysis of fractionated irradiated {kappa}-carrageenan oligomers as plant growth promoter

    Energy Technology Data Exchange (ETDEWEB)

    Abad, L.V., E-mail: [Philippine Nuclear Research Institute, Commonwealth Avenue, Diliman, Quezon City (Philippines); Saiki, S.; Nagasawa, N. [Quantum Beam Science Directorate, Japan Atomic Energy Agency, 1233 Watanuki, Takasaki, Gunma 370-1292 (Japan); Kudo, H.; Katsumura, Y. [Graduate School of Engineering, The University of Tokyo, 2-22 Shirakata-Shirane, Tokai, Naka, Ibaraki 319-1188 (Japan); De La Rosa, A.M. [Philippine Nuclear Research Institute, Commonwealth Avenue, Diliman, Quezon City (Philippines)


    The optimum plant growth promoting effect in irradiated {kappa}-carrageenan is known to be of Mw<10,000. This is obtained by irradiating {kappa}-carrageenan at a dose of 100 kGy in solid and at 2 kGy in 1% aqueous solution. Kappa carrageenan irradiated at these doses was fractionated at different Mw ranges. The isolated fraction with a Mw of 3-10 kDa was analyzed by NMR. The chemical shifts of {sup 13}C and {sup 1}H spectra indicated that the basic functional structure of {kappa}-carrageenan (alternating D-galactose-4-sulfate and 3,6-anhydro-D-galactose dimer) remains intact at a Mw of 3-10 kDa. No radiolytic products were detected at this range. - Highlights: > Irradiated {kappa}-carrageenan fractions with Mw<3 kDa contained higher carbonyl bonds. > {sup 1}H NMR and {sup 13}C spectra of irradiated {kappa}-carrageenan were similar to references. > {kappa}-Carrageenan oligomers with Mw of 3-10 kDa may be suitable as plant growth promoter.

  17. Reference intervals and physiologic alterations in hematologic and biochemical values of free-ranging desert tortoises in the Mojave Desert (United States)

    Christopher, Mary M.; Berry, Kristin H.; Wallis, I.R.; Nagy, K.A.; Henen, B.T.; Peterson, C.C.


    Desert tortoise (Gopherus agassizii) populations have experienced precipitous declines resulting from the cumulative impact of habitat loss, and human and disease-related mortality. Evaluation of hematologic and biochemical responses of desert tortoises to physiologic and environmental factors can facilitate the assessment of stress and disease in tortoises and contribute to management decisions and population recovery. The goal of this study was to obtain and analyze clinical laboratory data from free-ranging desert tortoises at three sites in the Mojave Desert (California, USA) between October 1990 and October 1995, to establish reference intervals, and to develop guidelines for the interpretation of laboratory data under a variety of environmental and physiologic conditions. Body weight, carapace length, and venous blood samples for a complete blood count and clinical chemistry profile were obtained from 98 clinically healthy adult desert tortoises of both sexes at the Desert Tortoise Research Natural area (western Mojave), Goffs (eastern Mojave) and Ivanpah Valley (northeastern Mojave). Samples were obtained four times per year, in winter (February/March), spring (May/June), summer (July/August), and fall (October). Years of near-, above- and below-average rainfall were represented in the 5 yr period. Minimum, maximum and median values, and central 95 percentiles were used as reference intervals and measures of central tendency for tortoises at each site and/or season. Data were analyzed using repeated measures analysis of variance for significant (P < 0.01) variation on the basis of sex, site, season, and interactions between these variables. Significant sex differences were observed for packed cell volume, hemoglobin concentration, aspartate transaminase activity, and cholesterol, triglyceride, calcium, and phosphorus concentrations. Marked seasonal variation was observed in most parameters in conjunction with reproductive cycle, hibernation, or seasonal

  18. Biofunctionalized magnetic hydrogel nanospheres of magnetite and {kappa}-carrageenan

    Energy Technology Data Exchange (ETDEWEB)

    Daniel-da-Silva, Ana L; Fateixa, Sara; Trindade, Tito; Goodfellow, Brian J; Gil, Ana M [Department of Chemistry, CICECO, University of Aveiro, 3810-193 Aveiro (Portugal); Guiomar, Antonio J [Department of Biochemistry and CNC, University of Coimbra, 3001-401 Coimbra (Portugal); Costa, Benilde F O [CEMDRX, Department of Physics, University of Coimbra, 3004-516 Coimbra (Portugal); Silva, Nuno J O, E-mail: ana.luisa@ua.p [Instituto de Ciencias de Materiales de Aragon, Departamento de Fisica de la Materia Condensada, Facultad de Ciencias, CSIC-Universidad de Zaragoza, 50009 Zaragoza (Spain)


    Magnetic hydrogel {kappa}-carrageenan nanospheres were successfully prepared via water-in-oil (w/o) microemulsions combined with thermally induced gelation of the polysaccharide. The size of the nanospheres (an average diameter () of about 50 and 75 nm) was modulated by varying the concentration of surfactant. The nanospheres contained superparamagnetic magnetite nanoparticles (8 nm), previously prepared by co-precipitation within the biopolymer. Carboxyl groups, at a concentration of about 4 mmol g{sup -1}, were successfully grafted at the surface of these magnetic nanospheres via carboxymethylation of the {kappa}-carrageenan. The carboxylated nanospheres were shown to be thermo-sensitive in the 37-45 {sup 0}C temperature range, indicating their potential as thermally controlled delivery systems for drugs and/or magnetic particles at physiological temperatures. Finally, preliminary results have been obtained for IgG antibody conjugation of the carboxylated nanospheres and the potential of these systems for bio-applications is discussed.

  19. Radiolysis studies of aqueous kappa-carrageenan

    Energy Technology Data Exchange (ETDEWEB)

    Abad, L.V., E-mail: [Philippine Nuclear Research Institute, Diliman, Quezon City (Philippines); Kudo, H. [Nuclear Professional School, Graduate School of Engineering, University of Tokyo, 2-22 Shirakata-Shirane, Tokai, Naka, Ibaraki 319-1188 (Japan); Saiki, S. [Nuclear Professional School, Graduate School of Engineering, University of Tokyo, 2-22 Shirakata-Shirane, Tokai, Naka, Ibaraki 319-1188 (Japan); Quantum Beam Science Directorate, Japan Atomic Energy Agency, 1233 Watanuki, Takasaki, Gunma 370-1292 (Japan); Nagasawa, N.; Tamada, M. [Quantum Beam Science Directorate, Japan Atomic Energy Agency, 1233 Watanuki, Takasaki, Gunma 370-1292 (Japan); Fu, H.; Muroya, Y. [Nuclear Professional School, Graduate School of Engineering, University of Tokyo, 2-22 Shirakata-Shirane, Tokai, Naka, Ibaraki 319-1188 (Japan); Lin, M.; Katsumura, Y. [Nuclear Professional School, Graduate School of Engineering, University of Tokyo, 2-22 Shirakata-Shirane, Tokai, Naka, Ibaraki 319-1188 (Japan); Advanced Science Research Center, Japan Atomic Energy Agency, 2-4 Shirakata-Shirane, Tokai, Naka, Ibaraki 319-1195 (Japan); Relleve, L.S.; Aranilla, C.T.; DeLaRosa, A.M. [Philippine Nuclear Research Institute, Diliman, Quezon City (Philippines)


    The effects on N{sub 2}O and N{sub 2} gas on the radiation degradation yield of aqueous kappa (kappa-) carrageenan were investigated. The G{sub d} of solution saturated with N{sub 2}O solution was expectedly much higher than in air (1.7 and 1.2 x 10{sup -7} mol J{sup -1}). On the other hand, a lower G{sub d} of 1.1 x 10{sup -7} mol J{sup -1} was obtained from kappa-carrageenan solution saturated with N{sub 2}. The rate constant of reaction of OH radicals with sonicated and irradiated kappa-carrageenan were determined using e-beam pulse radiolysis. The rate constant of OH{sup c}entre dot interaction with sonicated kappa-carrageenan decreased with decreasing molecular weight. On the other hand, the OH{sup c}entre dot interaction with irradiated kappa-carrageenan decreased but did not vary significantly with decreasing molecular weight. Metal ion (Na{sup +}) induced conformational transition into helical form decreased the rate constant of OH{sup c}entre dot reaction with kappa-carrageenan. Likewise, the G{sub d} in aqueous form was affected by the conformational state of kappa-carrageenan. The helical conformation gave a lower G{sub d} (7 x 10{sup -8} mol J{sup -1}) than the coiled conformation (G{sub d} = 1.2 x 10{sup -7} mol J{sup -1}).

  20. Calibration of the linear response range of x-ray imaging plates and their reader based on image grayscale values (United States)

    Ren, Kuan; Xu, Tao; Zheng, Jianhua; Dong, Jianjun; Wei, Minxi; Li, Chaoguang; Cao, Zhurong; Du, Huabing; Yan, Ji; Yang, Guohong; Yi, Rongqing; Zhang, Jiyan; Huang, Tianxuan; Liu, Shenye; Wang, Feng; Yang, Zhiwen; Li, Jin; Chen, Yaohua; Lan, Ke; Ren, Guoli; Liu, Jie; Ding, Yongkun; Jiang, Shaoen


    X-ray imaging plates are one of the most important X-ray imaging detectors and are widely used in inertial-confinement fusion experiments. However, their linear response range, which is the foundation of their quantitative data analysis, has not been sufficiently deeply investigated. In this work, we develop an X-ray fluorescer calibration system and carefully explore the linear response range of X-ray imaging plates. For the first time, nearly the entire grayscale range of the X-ray imaging plate linear response—7819-64 879 in the range of 0-65 535—has been observed. Further, we discuss the uncertainties involved in the calibration process. This work demonstrates the excellent linear response qualities of X-ray imaging plates and provides a significant foundation for expanding their quantitative applied range.

  1. Dichotomous actions of NF-kappaB signaling pathways in heart. (United States)

    Dhingra, Rimpy; Shaw, James A; Aviv, Yaron; Kirshenbaum, Lorrie A


    Despite the substantial progress in heart research over the past two decades heart failure still remains a major cause of morbidity and mortality in North America and is reaching pandemic proportions worldwide. Though the underlying causes are varied, the functional loss of contractile myocytes through apoptosis, necrosis, and autophagy has emerged a central unifying theme to explain diminished cardiac performance in individuals with heart failure. At the molecular level, there has been considerable interest in understanding the signaling pathways that regulate cell death in the heart with specific interest in the extrinsic and intrinsic cell death pathways. The cellular factor nuclear factor-kappaB (NF-kappaB) is a key transcription factor involved in the regulation of a wide range of genes involved in cellular process including inflammation, immune cell maturation, cell proliferation, and, most recently, cell survival. NF-kappaB signaling is important for the normal cellular growth and is a major target of inflammatory cytokines. Several studies have highlighted a protective role of NF-kappaB in the heart under certain circumstances including hypoxic or ischemic myocardial injury. The diverse nature and involvement of NF-kappaB in regulation of vital cellular processes including cell survival notably in the post-mitotic heart has sparked considerable interest in understanding the signaling pathways involved in regulating NF-kappaB in the heart under normal and pathological conditions. However, whether NF-kappaB is adaptive, maladaptive or is a homeostatic response to cardiac injury may simply depend on the context and timing of its activation. In this forum we discuss NF-kappaB signaling pathways and therapeutic opportunities to modulate NF-kappaB activity in heart failure.

  2. Characterization of NF-kappa B/I kappa B proteins in zebra fish and their involvement in notochord development. (United States)

    Correa, Ricardo G; Tergaonkar, Vinay; Ng, Jennifer K; Dubova, Ilir; Izpisua-Belmonte, Juan Carlos; Verma, Inder M


    Although largely involved in innate and adaptive immunity, NF-kappa B plays an important role in vertebrate development. In chicks, the inactivation of the NF-kappa B pathway induces functional alterations of the apical ectodermal ridge, which mediates limb outgrowth. In mice, the complete absence of NF-kappa B activity leads to prenatal death and neural tube defects. Here, we report the cloning and characterization of NF-kappa B/I kappa B proteins in zebra fish. Despite being ubiquitously expressed among the embryonic tissues, NF-kappa B/I kappa B members present distinct patterns of gene expression during the early zebra fish development. Biochemical assays indicate that zebra fish NF-kappa B proteins are able to bind consensus DNA-binding (kappa B) sites and inhibitory I kappa B alpha proteins from mammals. We show that zebra fish I kappa B alphas are degraded in a time-dependent manner after induction of transduced murine embryo fibroblasts (MEFs) and that these proteins are able to rescue NF-kappa B activity in I kappa B alpha(-/-) MEFs. Expression of a dominant-negative form of the murine I kappa B alpha (mI kappa B alpha M), which is able to block NF-kappa B in zebra fish cells, interferes with the notochord differentiation, generating no tail (ntl)-like embryos. This phenotype can be rescued by coinjection of the T-box gene ntl (Brachyury homologue), which is typically required for the formation of posterior mesoderm and axial development, suggesting that ntl lies downstream of NF-kappa B . We further show that ntl and Brachyury promoter regions contain functional kappa B sites and NF-kappa B can directly modulate ntl expression. Our study illustrates the conservation and compatibility of NF-kappa B/I kappa B proteins among vertebrates and the importance of NF-kappa B pathway in mesoderm formation during early embryogenesis.

  3. Using Kappa Functions to Characterize Outer Heliosphere Proton Distributions in the Presence of Charge-exchange (United States)

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


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


    Energy Technology Data Exchange (ETDEWEB)

    Zirnstein, E. J.; McComas, D. J., E-mail:, E-mail: [Southwest Research Institute, San Antonio, TX 78228 (United States)


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

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

    Energy Technology Data Exchange (ETDEWEB)

    Choi, C.-R.; Min, K.-W. [Department of Physics, Korea Advanced Institute of Science and Technology, Taejon 305-701 (Korea, Republic of); Rhee, T.-N. [National Fusion Research Institute, Daejeon 305-333 (Korea, Republic of)


    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.

  6. Electronic transmission and switch effect in kappa-component Fibonacci nanowires. (United States)

    Li, Jia; Zhang, Ruili; Li, De; Peng, Ruwen; Wang, Mu


    We present the electronic transport in the k-component Fibonacci (KCF) nanowires, in which kappa different incommensurate intervals are arranged according to a substitution rule. For the KCF nanowires with an identical kappa, by increasing the length of the nanowire, the minima in transmission extend gradually into the band gap over which the transmission is blocked. Meanwhile more transmission peaks appear. For finite KCF nanowire, by increasing the number of different incommensurate intervals kappa, the width of electronic band gap is enlarged. Moreover, when the value of kappa is sufficiently large, the transmission is shut off, except at a few resonant energies. These properties make it possible to use the KCF nanowires as switching devices. Furthermore, a dimensional spectrum of singularities associated with the transmission spectrum demonstrates that the electronic propagation in the KCF nanowire shows multifractality. These investigations open a unique way to control quantum transport in nanodevices.

  7. On Hopf algebroid structure of kappa-deformed Heisenberg algebra

    CERN Document Server

    Lukierski, Jerzy; Woronowicz, Mariusz


    The $(4+4)$-dimensional $\\kappa$-deformed quantum phase space as well as its $(10+10)$-dimensional covariant extension by the Lorentz sector can be described as Heisenberg doubles: the $(10+10)$-dimensional quantum phase space is the double of $D=4$ $\\kappa$-deformed Poincar\\'e Hopf algebra $\\mathbb{H}$ and the standard $(4+4)$-dimensional space is its subalgebra generated by $\\kappa$-Minkowski coordinates $\\hat{x}_\\mu$ and corresponding commuting momenta $\\hat{p}_\\mu$. Every Heisenberg double appears as the total algebra of a Hopf algebroid over a base algebra which is in our case the coordinate sector. We exhibit the details of this structure, namely the corresponding right bialgebroid and the antipode map. We rely on algebraic methods of calculation in Majid-Ruegg bicrossproduct basis. The target map is derived from a formula by J-H. Lu. The coproduct takes values in the bimodule tensor product over a base, what is expressed as the presence of coproduct gauge freedom.

  8. An interdisciplinary approach to integrate a range of agro-landscape values as proposed by representatives of various disciplines.

    NARCIS (Netherlands)

    Mansvelt, van J.D.


    A Concerted Action has been initiated to discuss the assessment of sustainable agro-landscape values in the EU. The objective is to find out how criteria and parameters can be defined that would help farmers, authorities and politicians to manage the agro-landscape towards sustainability and

  9. An interdisciplinary approach to integrate a range of agro-landscape values as proposed by representatives of various disciplines.

    NARCIS (Netherlands)

    Mansvelt, van J.D.


    A Concerted Action has been initiated to discuss the assessment of sustainable agro-landscape values in the EU. The objective is to find out how criteria and parameters can be defined that would help farmers, authorities and politicians to manage the agro-landscape towards sustainability and socio/c

  10. Flat-topped mountain ranges: Their global distribution and value for understanding the evolution of mountain topography (United States)

    Calvet, Marc; Gunnell, Yanni; Farines, Bernard


    Extensive tracts of low-gradient topography in steep mountain ranges, either forming rangetop plateaus or terraced pediments on range flanks, are widely distributed in mountain belts around the world. Before the advent of plate tectonics, such populations of planar landforms were interpreted as vestiges of a post-orogenic raised peneplain, i.e., a low-gradient land surface resulting from the decay, during long intervals of base-level stability, of a previous mountain range that was subsequently raised once again to great elevations-thus forming a new mountain range. This two-stage model has been challenged by theories that advocate continuity in tectonic processes and more gradual changes in base level, and thus expect a more immediate and proportionate response of geomorphic systems. Here we present a global survey of erosion surfaces in mountain ranges and put existing theories and empirical evidence into a broad perspective calling for further research into the rates and regimes of long-term mountain evolution. The resulting library of case studies provides opportunities for comparative analysis and helps to classify the landform mosaics that are likely to arise from the interplay between (i) crustal regimes, which at convergent plate margins need be neither uniform nor steady at all times; (ii) radiation-driven and gravity-driven geomorphic regimes, which are mainly determined by crustal boundary conditions and climate; and (iii) paleogeography, through which clues about base-level changes can be obtained. We examine intracratonic and plate-margin settings, with examples from thin-skinned fold belts, thick-skinned fold belts, island-arc and other subduction-related settings, and bivergent collisional orogens. Results reveal that the existence of erosion surfaces is not a simple function of geodynamic setting. Although some erosion surfaces are pre-orogenic, evidence about their predominantly post-orogenic age is supported by apatite fission-track and helium

  11. Measuring agreement of administrative data with chart data using prevalence unadjusted and adjusted kappa

    Directory of Open Access Journals (Sweden)

    Hemmelgarn Brenda


    Full Text Available Abstract Background Kappa is commonly used when assessing the agreement of conditions with reference standard, but has been criticized for being highly dependent on the prevalence. To overcome this limitation, a prevalence-adjusted and bias-adjusted kappa (PABAK has been developed. The purpose of this study is to demonstrate the performance of Kappa and PABAK, and assess the agreement between hospital discharge administrative data and chart review data conditions. Methods The agreement was compared for random sampling, restricted sampling by conditions, and case-control sampling from the four teaching hospitals in Alberta, Canada from ICD10 administrative data during January 1, 2003 and June 30, 2003. A total of 4,008 hospital discharge records and chart view, linked for personal unique identifier and admission date, for 32 conditions of random sampling were analyzed. The restricted sample for hypertension, myocardial infarction and congestive heart failure, and case-control sample for those three conditions were extracted from random sample. The prevalence, kappa, PABAK, positive agreement, negative agreement for the condition was compared for each of three samples. Results The prevalence of each condition was highly dependent on the sampling method, and this variation in prevalence had a significant effect on both kappa and PABAK. PABAK values were obviously high for certain conditions with low kappa values. The gap between these two statistical values for the same condition narrowed as the prevalence of the condition approached 50%. Conclusion Kappa values varied more widely than PABAK values across the 32 conditions. PABAK values should usually not be interpreted as measuring the same agreement as kappa in administrative data, particular for the condition with low prevalence. There is no single statistic measuring agreement that captures the desired information for validity of administrative data. Researchers should report kappa, the

  12. $\\kappa$-Deformation and Spectral Triples

    CERN Document Server

    Iochum, B; Schücker, Th; Sitarz, A; 10.5506/APhysPolBSupp.4.305


    The aim of the paper is to answer the following question: does $\\kappa$-deformation fit into the framework of noncommutative geometry in the sense of spectral triples? Using a compactification of time, we get a discrete version of $\\kappa$-Minkowski deformation via $C^*$-algebras of groups. The dynamical system of the underlying groups (including some Baumslag--Solitar groups) is used in order to construct \\emph{finitely summable} spectral triples. This allows to bypass an obstruction to finite-summability appearing when using the common regular representation.

  13. Strong Langmuir turbulence in Kappa distributed plasmas

    Energy Technology Data Exchange (ETDEWEB)

    Liu Sanqiu [Department of Physics and School of Materials Science and Engineering, Nanchang University, Nanchang, 330047 (China); Chen Hui [School of Materials Science and Engineering, Nanchang University, Nanchang 330047 (China)


    Superthermal electrons are often observed in space and astrophysics and can be appropriate modeled by the family of Kappa distribution functions. Taking the nonlinear wave-wave, wave-particle interactions and the effect of superthermal electrons into account, the strong Langmuir turbulence is investigated in kinetic regime. The modified Zakharov equations are obtained for the case of no damping or driving terms. On the basis of these equations, dynamics of collapse have been studied by the means of the general virial theorem, and the collapse thresholds which are strong modified by superthermal index {kappa}{sub e} are given.

  14. Spectroscopy of a \\kappa-Cygnid fireball afterglow

    CERN Document Server

    Madiedo, José M


    A bright fireball with an absolute magnitude of -10.5 $\\pm$ 0.5 was recorded over the South of Spain on August 15, 2012. The atmospheric trajectory, radiant and heliocentric orbit of this event are calculated. These data show that the parent meteoroid belonged to the \\kappa-Cygnid meteoroid stream. The emission spectrum of this bolide, which was obtained in the wavelength range between 350 and 800 nm, suggests a chondritic nature for the progenitor meteoroid. Besides, the spectrum of the meteoric afterglow was also recorded for about 0.7 seconds. The evolution with time of the intensity of the main emission lines identified in this signal is discussed.

  15. Retention of Underrepresented Minority Faculty: Strategic Initiatives for Institutional Value Proposition Based on Perspectives from a Range of Academic Institutions (United States)

    Whittaker, Joseph A.; Montgomery, Beronda L.; Martinez Acosta, Veronica G.


    The student and faculty make-up of academic institutions does not represent national demographics. Racial and ethnic minorities are disproportionately underrepresented nationally, and particularly at predominantly white institutions (PWIs). Although significant efforts and funding have been committed to increasing points of access or recruitment of under-represented minority (URM) students and faculty at PWIs, these individuals have not been recruited and retained at rates that reflect their national proportions. Underrepresentation of URMs is particularly prevalent in Science, Technology, Engineering, and Mathematics (STEM) disciplines. This reality represents a national crisis given a predicted shortage of workers in STEM disciplines based on current rates of training of all individuals, majority and URM, and the intersection of this limitation with persistent challenges in the recruitment, training, retention and advancement of URMs who will soon represent the largest pool of future trainees. An additional compounding factor is the increasingly disproportionate underrepresentation of minorities at higher professorial and administrative ranks, thus limiting the pool of potential mentors who are correlated with successful shepherding of URM students through STEM training and development. We address issues related to improving recruitment and retention of URM faculty that are applicable across a range of academic institutions. We describe challenges with recruitment and retention of URM faculty and their advancement through promotion in the faculty ranks and into leadership positions. We offer specific recommendations, including identifying environmental barriers to diversity and implementing strategies for their amelioration, promoting effective and innovative mentoring, and addressing leadership issues related to constructive change for promoting diversity. PMID:26240521

  16. Inpatient Glucose Values: Determining the Nondiabetic Range and Use in Identifying Patients at High Risk for Diabetes. (United States)

    Rhee, Mary K; Safo, Sandra E; Jackson, Sandra L; Xue, Wenqiong; Olson, Darin E; Long, Qi; Barb, Diana; Haw, J Sonya; Tomolo, Anne M; Phillips, Lawrence S


    Many individuals with diabetes remain undiagnosed, leading to delays in treatment and higher risk for subsequent diabetes complications. Despite recommendations for diabetes screening in high risk groups, the optimal approach is not known. We evaluated the utility of inpatient glucose levels as an opportunistic screening tool for identifying patients at high risk for diabetes. We retrospectively examined 462,421 patients in the national VA healthcare system, hospitalized on medical/surgical services in 2000-2010, for ≥3 days, with ≥2 inpatient random plasma glucose (RPG) measurements. All had continuity of care - ≥1 primary care visit and ≥1 glucose measure within 2 years before hospitalization and yearly for ≥3 years after discharge. Glucose levels during hospitalization and incidence of diabetes within 3 years after discharge in patients without diabetes were evaluated. Patients had mean age 65.0 years, BMI 29.9, and were 96% male, 71% white, and 18% black. Preexisting diabetes was present in 39.4%, 1.3% were diagnosed during hospitalization, 8.1% diagnosed RPG (112 mg/dl [6.2 mmol/L]). Having at least two RPGs >140 mg/dl (>7.8 mmol/L), the 95(th) percentile of NonDM hospital glucose, provided 81% specificity for identifying incident diabetes <3 years post-discharge. Screening for diabetes could be considered in patients with at least two hospital glucoses at/above the 95th percentile of the nondiabetic range (141 mg/dl [7.8 mmol/L]). Copyright © 2017. Published by Elsevier Inc.

  17. The role of NF-kappaB in endometriosis. (United States)

    Kaponis, Apostolos; Iwabe, Tomio; Taniguchi, Fuminori; Ito, Masayuki; Deura, Imari; Decavalas, George; Terakawa, Naoki; Harada, Tasuku


    The nuclear factor kappaB (NF-kappaB) is a ubiquitously expressed transcription factor playing vital roles in innate immunity and other processes involving cellular survival, proliferation, and differentiation. This review highlights the importance of NF-kappaB in the pathophysiology of endometriosis. Constitutive activation of NF-kappaB has been shown in endometriotic lesions. Complex interactions of NF-kappaB with steroid receptors and apoptotic molecules in endometriosis resulting in opposing roles of NF-kappaB are discussed. NF-kappaB regulates the expression of cytokines mediating autocrine self-amplifying cycles of cytokine release and NF-kappaB activation, leading to maintenance of inflammatory reactions in endometriosis. NF-kappaB can contribute to the increased ability of endometriotic cells to invade and adhere to the peritoneal surface by regulating the expression of matrix metaloproteinases. We are presenting the role of NF-kappaB to regulate vascularization and oxidative stress in endometriotic cells. Effects of drugs used for the treatment of endometriosis on NF-kappaB pathway are presented and we show how drugs that inhibit the NF-kappaB can mediate the progression of endometriosis. Novel therapeutic strategies involving the NF-kappaB and applied in endometriosis are also discussed.

  18. Automatic Kappa Angle Estimation for Air Photos Based on Phase Only Correlation (United States)

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


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

  19. An Empirical Determination of the Dust Mass Absorption Coefficient, $\\kappa_{d}$, Using the Herschel Reference Survey

    CERN Document Server

    Clark, Christopher J R; Gomez, Haley L; Davies, Jonathan I


    We use the published photometry and spectroscopy of 22 galaxies in the Herschel Reference Survey to determine that the value of the dust mass absorption coefficient $\\kappa_{d}$ at a wavelength of 500 $\\mu m$ is $\\kappa_{500} = 0.051^{+0.070}_{-0.026}\\,{\\rm m^{2}\\,kg^{-1}}$. We do so by taking advantage of the fact that the dust-to-metals ratio in the interstellar medium of galaxies appears to be constant. We argue that our value for $\\kappa_{d}$ supersedes that of James et al. (2002) -- who pioneered this approach for determining $\\kappa_{d}$ -- because we take advantage of superior data, and account for a number of significant systematic effects that they did not consider. We comprehensively incorporate all methodological and observational contributions to establish the uncertainty on our value, which represents a marked improvement on the oft-quoted 'order-of-magnitude' uncertainty on $\\kappa_{d}$. We find no evidence that the value of $\\kappa_{d}$ differs significantly between galaxies, or that it correla...

  20. [Cystine as a risk factor of the stone formation in kidney: the reference value range of urinary excretion, the stage diagnosis of cystine metabolism disorder]. (United States)

    Gres, A A; Nitkin, D M; Juraha, T M; Sivakow, A A


    to define the reference value ranges of cystine, lysine and arginine urinary excretion relative to creatinine in the morning urine samples for the metabolic disorders diagnosis leading to the formation of urinary stones. the study involved 695 healthy individuals aged 1-17 and 1564 patients with urolithiasis aged 7-45. The content of cystine in the urine samples was determined by high performance liquid chromatography. The chemical composition of urinary stones was investigated by methods of the qualitative chemical reaction and the crystals microscopy. the reference value ranges of cystine, lysine and arginine urinary excretion relative to creatinine in the morning urine samples were developed in the age aspect. Excess in cystine level in the urine samples of the relatively healthy individuals detected in 1.4% of cases. From 1564 urinary stones submitted for analysis, the frequency of cystine stones was 0.8%. for the objective assessment of the cystine metabolism status the evaluation of the degree of cystinuria is necessary in order to form the risk group for cystine nephrolithiasis. The reference value ranges of cystine urinary excretion developed in the age aspect and "cystine / creatinine index" in morning urine samples will provide the opportunity to identify the state of the cystine exchange from early childhood and develop differentiated program for the prevention of stone formation in the kidneys.

  1. Properties of sigma and kappa Production Amplitudes

    CERN Document Server

    Ishida, M; Ishida, Muneyuki; Ishida, Shin


    Our method of analysis, which led to existence of sigma and kappa mesons, is reviewed and examined from a viewpoint of general S-matrix. It is shown that the method is consistent with the constraints from chiral symmetry and unitarity. Accordingly the long-believed common analyses of pipi (Kpi) scattering and production processes, based on elastic unitarity, prove to lose its theoretical base. The observed phase motion by 180 degrees of sigma shows also the validity of our method.

  2. Tissue oximetry: a comparison of mean values of regional tissue saturation, reproducibility and dynamic range of four NIRS-instruments on the human forearm

    DEFF Research Database (Denmark)

    Hyttel-Sørensen, Simon; Sorensen, Line C; Riera, Joan


    We compared absolute values of regional tissue hemoglobin saturation (StO(2)), reproducibility, and dynamic range of four different instruments on the forearm of adults. The sensors were repositioned 10 times on each subject. Dynamic range was estimated by exercise with subsequent arterial...... occlusion. Mean StO(2) was 70.1% ± 6.7 with INVOS 5100, 69.4% ± 5.0 with NIRO 200 NX, 63.4% ± 4.5 with NIRO 300, and 60.8% ± 3.6 with OxyPrem. The corresponding reproducibility S(w) was 5.4% (CI 4.4-6.9), 4.4% (CI 3.5-5.2), 4.1% (CI 3.3-4.9), and 2.7% (CI 2.2-3.2), respectively. The dynamic ranges ¿StO(2......) were 45.0%, 46.8%, 44.8%, and 27.8%, respectively. In conclusion, the three commercial NIRS instruments showed different absolute values, whereas reproducibility and dynamic range were quite similar....

  3. Tissue oximetry: a comparison of mean values of regional tissue saturation, reproducibility and dynamic range of four NIRS-instruments on the human forearm

    DEFF Research Database (Denmark)

    Hyttel-Sørensen, Simon; Sorensen, Line C; Riera, Joan


    We compared absolute values of regional tissue hemoglobin saturation (StO(2)), reproducibility, and dynamic range of four different instruments on the forearm of adults. The sensors were repositioned 10 times on each subject. Dynamic range was estimated by exercise with subsequent arterial...... occlusion. Mean StO(2) was 70.1% ± 6.7 with INVOS 5100, 69.4% ± 5.0 with NIRO 200 NX, 63.4% ± 4.5 with NIRO 300, and 60.8% ± 3.6 with OxyPrem. The corresponding reproducibility S(w) was 5.4% (CI 4.4-6.9), 4.4% (CI 3.5-5.2), 4.1% (CI 3.3-4.9), and 2.7% (CI 2.2-3.2), respectively. The dynamic ranges ΔStO(2......) were 45.0%, 46.8%, 44.8%, and 27.8%, respectively. In conclusion, the three commercial NIRS instruments showed different absolute values, whereas reproducibility and dynamic range were quite similar....

  4. Differential forms and {kappa}-Minkowski spacetime from extended twist

    Energy Technology Data Exchange (ETDEWEB)

    Juric, Tajron; Meljanac, Stjepan [Rudjer Boskovic Institute, Zagreb (Croatia); Strajn, Rina [Jacobs University Bremen, Bremen (Germany)


    We analyze bicovariant differential calculus on {kappa}-Minkowski spacetime. It is shown that corresponding Lorentz generators and noncommutative coordinates compatible with bicovariant calculus cannot be realized in terms of commutative coordinates and momenta. Furthermore, {kappa}-Minkowski space and NC forms are constructed by twist related to a bicrossproduct basis. It is pointed out that the consistency condition is not satisfied. We present the construction of {kappa}-deformed coordinates and forms (super-Heisenberg algebra) using extended twist. It is compatible with bicovariant differential calculus with {kappa}-deformed igl(4)-Hopf algebra. The extended twist leading to {kappa}-Poincare-Hopf algebra is also discussed. (orig.)

  5. Lignans from Saururus chinensis inhibiting the transcription factor NF-kappaB. (United States)

    Hwang, Bang Yeon; Lee, Jeong Hyung; Nam, Jeong Bum; Hong, Young Soo; Lee, Jung Joon


    The sesquineolignans, saucerneol D and saucerneol E were isolated from the roots of Saururus chinensis together with four known lignans, manassantin A, manassantin B, (-)-saucerneol methyl ether, and (+)-saucernetin. Structure elucidation was based on the analysis of spectroscopic data and anti-inflammatory activity was studied using HeLa cells transfected with NF-kappaB reporter construct. All compounds except for (+)-saucernetin inhibited NF-kappaB dependent reporter gene expression with IC50 values of 2.5-16.9 microM.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kumar Kuri, Deep, E-mail:; Das, Nilakshi, E-mail: [Department of Physics, Tezpur University, Tezpur, Assam 784 028 (India)


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

  7. Detection of kappa and lambda light chain monoclonal proteins in human serum: automated immunoassay versus immunofixation electrophoresis. (United States)

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


    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.


    Directory of Open Access Journals (Sweden)

    Fabio Alexander Molina Cote


    thixotropic behavior in kappa, kappa I.II, tara gum and their mixtures evaluated. Brines containing kappa, kappa I.II and kappa-kappa I.II showed lower viscosity values than blends with tara gum which produced more viscosity in cold conditions than kappas. In the quadratic arrangement of mixtures, it was observed in terms of maximum thixotropic index the more optimal region was for mixture containing kappa I.II-tara gum (79% and 21%, correspondly with a significant level of 0.05.

  9. Receptor tyrosine phosphatase R-PTP-kappa mediates homophilic binding

    DEFF Research Database (Denmark)

    Sap, J; Jiang, Y P; Friedlander, D


    Receptor tyrosine phosphatases (R-PTPases) feature PTPase domains in the context of a receptor-like transmembrane topology. The R-PTPase R-PTP-kappa displays an extracellular domain composed of fibronectin type III motifs, a single immunoglobulin domain, as well as a recently defined MAM domain (Y.......-P. Jiang, H. Wang, P. D'Eustachio, J.M. Musacchio, J. Schlessinger, and J. Sap, Mol. Cell. Biol. 13:2942-2951, 1993). We report here that R-PTP-kappa can mediate homophilic intercellular interaction. Inducible expression of the R-PTP-kappa protein in heterologous cells results in formation of stable...... cellular aggregates strictly consisting of R-PTP-kappa-expressing cells. Moreover, the purified extracellular domain of R-PTP-kappa functions as a substrate for adhesion by cells expressing R-PTP-kappa and induces aggregation of coated synthetic beads. R-PTP-kappa-mediated intercellular adhesion does...

  10. Glucocorticoid receptor and nuclear factor kappa-b affect three-dimensional chromatin organization

    NARCIS (Netherlands)

    Kuznetsova, T.; Wang, S.Y.; Rao, N.A.; Mandoli, A.; Martens, J.H.; Rother, N; Aartse, A.; Groh, L.; Janssen-Megens, E.M.; Li, G.; Ruan, Y.; Logie, C.; Stunnenberg, H.G.


    BACKGROUND: The impact of signal-dependent transcription factors, such as glucocorticoid receptor and nuclear factor kappa-b, on the three-dimensional organization of chromatin remains a topic of discussion. The possible scenarios range from remodeling of higher order chromatin architecture by activ

  11. Glucocorticoid receptor and nuclear factor kappa-b affect three-dimensional chromatin organization

    NARCIS (Netherlands)

    Kuznetsova, T.; Wang, S.Y.; Rao, N.A.; Mandoli, A.; Martens, J.H.; Rother, N; Aartse, A.; Groh, L.; Janssen-Megens, E.M.; Li, G.; Ruan, Y.; Logie, C.; Stunnenberg, H.G.


    BACKGROUND: The impact of signal-dependent transcription factors, such as glucocorticoid receptor and nuclear factor kappa-b, on the three-dimensional organization of chromatin remains a topic of discussion. The possible scenarios range from remodeling of higher order chromatin architecture by

  12. Disaggregating the contribution of local dispersion and long-range transport to the high PM10 values measured in a Mediterranean urban environment. (United States)

    Paschalidou, A K; Kassomenos, P; Karanikola, P


    The EU daily PM10 limit-value of 50 μg m(-3) is frequently breached in the center of Athens, Greece. A total of 852 daily exceedances were recorded in the city-center during the 6-year period 2001-2006. These exceedances were more frequent in winter, followed by spring and autumn. For the needs of the study, the PM10 episodes (i.e., concentrations 30% above the median value) were grouped in two categories: (a) the City-Center episodes and (b) the Wider Metropolitan Area episodes. It was assumed that City-Center episodes occurred when elevated PM10 values were measured in the city-center exclusively, whereas Wider Metropolitan Area episodes occurred when high PM10 concentrations were also measured in the suburbs. Then back-trajectory cluster analysis was performed in an attempt to associate high PM10 levels with local dispersion or long-range transport. The City-Center episodes were associated according to the origin of air parcels with six types of air-masses (slow and fast moving from northern, northeasterly and southern directions, or stagnated around Athens) and were mainly due to traffic or other local sources, whereas the Wider Metropolitan Area episodes were mainly associated with air-masses coming from southern directions and were linked to long-range transport. On the whole, the analysis provided evidence of Sahara-dust events and sea-spray transportation.

  13. An Italian national multicenter study for the definition of reference ranges for normal values of peripheral blood lymphocyte subsets in healthy adults. (United States)

    Santagostino, A; Garbaccio, G; Pistorio, A; Bolis, V; Camisasca, G; Pagliaro, P; Girotto, M


    Reference ranges are necessary in clinical chemistry and hematology to compare an observed value and to provide meaningful information. The aim of this multicenter study was the definition of reference ranges of the relative and absolute numbers of lymphocyte subsets by evaluating a large cohort of healthy adults and by using a standard protocol to reduce the variability in both sample preparation methodology and flow cytometer operation. Other aims of this study were the evaluation of the influence of sex, age, obesity, smoking, sport and some methodological variables on lymphocyte subsets and the comparison of differential white blood cell values obtained by flow cytometry and those obtained by hematology counters. Blood samples from 1311 healthy adults (blood donors and volunteers chosen according to the Italian law for donor selection) were analyzed to study, by flow cytometry, the immunophenotype of lymphocyte subsets and their distribution in terms of percentages and absolute values. Pre-analytical and analytical phases were performed according to the guidelines of the International Federation of Clinical Chemistry (IFCC) and the Italian Group of Cytometry (GIC). T cells were defined by the expression of CD3; T subpopulations by the coexpression of CD4 or CD8 or HLA-DR; B-lymphocytes were identified by the expression of CD19 while natural killer lymphocytes were identified by positivity of CD16 and/or CD56 without CD3. We calculated, for each laboratory and for all data collected, the frequency distribution percent values and absolute values of each lymphocyte subset. The influence of age, sex, smoking, obesity and sport was calculated by the t-test. The influence of some methodological variables was calculated by the t-test and multiple regression test. Fifty-three flow cytometry laboratories at different institutions in Italy participated in this study. Data was obtained from 1311 healthy adults aged from 18 to 70; 968 phenotype analyses (74%) were

  14. 毛刺对非相干测距值的影响%Influence of Glitch on Non-coherent Ranging Value

    Institute of Scientific and Technical Information of China (English)



    针对实时监测目标飞行器距离在地空信息传输系统中具有的重要作用,基于非相干测距技术,介绍了一种根据上下行链路数据产生测距脉冲的算法,分析了该算法容易产生毛刺的原因以及对测距结果造成的危害,对比4种消除毛刺方法的优劣,提出了一种改进算法,并对2种算法进行仿真对比。仿真及分析结果表明,改进算法能成功消除毛刺,经过实际系统测试,能有效提高测距值的准确度,且性能良好,满足系统设计要求。%Target aero-craft distance real-time monitoring is important in Ground-Air communication system. Based on non-coher-ent ranging technology,an algorithm is introduced generating ranging pulse according to uplink and downlink data. And analysis is giv-en on the reasons why it tends to produce glitch easily and its harm to the ranging value. Then it compares advantages and disadvanta-ges of four methods which can eliminate glitch. An improved algorithm is put forward. Comparison of two algorithms is done by simula-tion. The result shows that the improved algorithm can eliminate the glitch successfully. In actual system testing,it can also improve the accuracy of ranging value effectively,and meet system design requirement with a good performance.

  15. Nonlinear plasma processes and the formation of electron kappa distribution (United States)

    Yoon, Peter


    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.

  16. Kappa Number Prediction of Acacia melanoxylon Unbleached Kraft Pulps using NIR-PLSR Models with a Narrow Interval of Variation

    Directory of Open Access Journals (Sweden)

    António J.A. Santos


    Full Text Available A total of 120 Acacia melanoxylon R. Br. (Australian blackwood stem discs, belonging to 20 trees from four sites in Portugal, were used in this study. The samples were kraft pulped under standard identical conditions targeted to a Kappa number of 15. A Near Infrared (NIR partial least squares regression (PLSR model was developed for the Kappa number prediction using 75 pulp samples with a narrow Kappa number variation range of 10 to 17. Very good correlations between NIR spectra of A. melanoxylon pulps and Kappa numbers were obtained. Besides the raw spectra, also pre-processed spectra with ten methods were used for PLS analysis (cross validation with 48 samples, and a test set validation was made with 27 samples. The first derivative spectra in the wavenumber range from 6110 to 5440 cm-1 yielded the best model with a root mean square error of prediction of 0.4 units of Kappa number, a coefficient of determination of 92.1%, and two PLS components, with the ratios of performance to deviation (RPD of 3.6 and zero outliers. The obtained NIR-PLSR model for Kappa number determination is sufficiently accurate to be used in screening programs and in quality control.

  17. Effects of kappa opioid receptor-selective agonists on responses of pelvic nerve afferents to noxious colorectal distension. (United States)

    Su, X; Sengupta, J N; Gebhart, G F


    The aim of this study was to examine the effects of kappa-opioid receptor selective agonists on responses of mechanosensitive afferent fibers in the pelvic nerve. Single-fiber recordings were made from pelvic nerve afferents in the decentralized S1 dorsal root of the rat. A total of 572 afferent fibers in the S1 dorsal root were identified by electrical stimulation of the pelvic nerve; 252 (44%) responded to noxious colorectal distension (CRD; 80 mmHg). Of these 252 fibers that responded to CRD, 100 were studied further. All 100 fibers gave monotonic increases in firing to increasing pressures of CRD. Eighty-eight fibers had low thresholds for response (mean: 3 mmHg) and 12 fibers had high-thresholds for response (mean: 28 mmHg). Responses of 17 fibers also were tested after instillation of 5% mustard oil (MO) into the colon. The resting activity of 16/17 fibers significantly increased after MO instillation; 13 (77%) also exhibited sensitization of responses to graded CRD when tested 30 min after intracolonic MO instillation. The effects of kappa1-opioid receptor preferring agonists (U50,488H, U69,593 and U62,066), the kappa2-opioid receptor preferring agonist bremazocine, and the kappa3-opioid receptor preferring agonist naloxone benzoylhydrazone (nalBzoH) were tested on responses of 64 mechanosensitive afferent fibers to noxious CRD. All five agonists dose-dependently inhibited afferent fiber responses to noxious CRD. Doses producing inhibition to 50% of the control response to CRD did not differ among the five agonists, ranging from approximately 4 to 15 mg/kg. The effects of kappa1, kappa2, and kappa3 receptor agonists were attenuated by naloxone; two kappa-opioid receptor-selective antagonists were ineffective. There were no differences in the dose-response relationships of these drugs for fibers recorded from untreated and irritant-treated colons. Conduction velocities of the fibers remained unaffected after high doses of all tested agonists. In an in vitro

  18. The radiant ephemerides of kappa-Cygnids from the IMO video database (United States)

    Triglav-Cekada, Mihaela


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

  19. Reproducibility of the Nottingham modification of the Scarff-Bloom-Richardson histological grading system and the complementary value of Ki-67 to this system

    Institute of Scientific and Technical Information of China (English)

    ZHANG Rui; CHEN Hui-jiao; WEI Bing; ZHANG Hong-ying; PANG Zong-guo; ZHU Hong; ZHANG Zhang; FU Jing; BU Hong


    Background The reproducibility of the Nottingham modification of the Scarff-Bloom-Richardson (NSBR) histological grading system for invasive breast cancer (IBC) adopted by the World Health Organization (WHO) has previously not been studied in Chinese hospitals. The proliferation marker, Ki-67, has been widely applied in detecting IBC. The objective of this study was to assess the reproducibility of the NSBR system among Chinese pathologists and the complementary value that Ki-67 brings to this system.Methods Four general pathologists graded 100 IBC cases independently, which had previously been graded by specialists in breast pathology. The interobserver reproducibility among four general pathologists and pairwise reproducibility between each of them and the specialists were assessed. The Ki-67 labeling index (Ki-67LI) was determined by immunohistochemistry, and its correlations with histological grade and survival were determined.Results With respect to interobserver reproducibility, NSBR grading was fairly reproducible (kappa=0.34); as for the components of NSBR grading, agreement was best for tubule formation (kappa=0.46), intermediate for nuclear pleomorphism (kappa=0.42), and poorest for mitotic count (kappa=0.28). In terms of pairwise reproducibility, agreement was fair to substantial with NSBR grading (kappa=0.30-0.69) and nuclear pleomorphism (kappa=0.28-0.69), moderate to substantial for tubule formation (kappa=0.51-0.78), and slight to substantial for mitotic count (kappa=0.19-0.71).There were characteristic Ki-67LI ranges for grades 1,2 and 3 tumors. Univariate analysis showed that Ki-67 was able to divide grade 2 patients into two different prognostic subgroups. Multivariate analysis of grade 2 patients with negative lymph node demonstrated that Ki-67 was an independent prognosticator for overall survival.Conclusions The reproducibility of grading by general pathologists could be enhanced. Specialization in breast pathology is essential for accurate

  20. Kappa distributions in the presence of a potential energy (United States)

    Livadiotis, George


    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 geophysical, space, and astrophysical plasmas, are characterized by a non-Maxwellian behavior, typically described by the so-called kappa distributions, or combinations thereof. Empirical kappa distributions have become increasingly widespread across plasma physics. A breakthrough in the field came with the connection of kappa distributions to non-extensive statistical mechanics. Understanding the statistical origin of kappa distributions was the cornerstone of further theoretical developments and applications, one of which is the generalization to the phase-space kappa distributions of a Hamiltonian with non-zero potentials. We present the theory behind the phase-space kappa distributions and discuss three important applications in collisionless plasmas: (i) origin of polytropic relation; (ii) gravitational field; (iii) barometric relation (i.e., pressure vs. altitude); and (iv) plasma magnetization.

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


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


    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 replac...

  2. Antinociceptive and hypothermic effects of Salvinorin A are abolished in a novel strain of kappa-opioid receptor-1 knockout mice. (United States)

    Ansonoff, Michael A; Zhang, Jiwen; Czyzyk, Traci; Rothman, Richard B; Stewart, Jeremy; Xu, Heng; Zjwiony, Jordan; Siebert, Daniel J; Yang, Feng; Roth, Bryan L; Pintar, John E


    Salvia divinorum is a natural occurring hallucinogen that is traditionally used by the Mazatec Indians of central Mexico. The diterpene salvinorin A was identified as an active component of S. divinorum over 20 years ago, but only recently has biochemical screening indicated that a molecular target of salvinorin A in vitro is the kappa-opioid receptor. We have examined whether salvinorin A, the C2-substituted derivative salvinorinyl-2-propionate, and salvinorin B can act as kappa-opioid receptor agonists in vivo. We found that following intracerebroventricular injection over a dose range of 1 to 30 microg of both salvinorin A and salvinorinyl-2-propionate produces antinociception in wild-type mice but not in a novel strain of kappa-opioid receptor knockout mice. Moreover, both salvinorin A and salvinorinyl-2-propionate reduce rectal body temperature, similar to conventional kappa-opioid receptor agonists, in a genotype-dependent manner. In addition, we determined that salvinorin A has high affinity for kappa 1- but not kappa 2-opioid receptors, demonstrating selectivity for this receptor subclass. Finally, treatment over the same dose range with salvinorin B, which is inactive in vitro, produced neither antinociceptive nor hypothermic effects in wild-type mice. These data demonstrate that salvinorin A is the active component of S. divinorum, selective for kappa(1)-opioid receptors, and that salvinorin A and specific structurally related analogs produce behavioral effects that require the kappa-opioid receptor.

  3. Kappa and q Indices: Dependence on the Degrees of Freedom

    Directory of Open Access Journals (Sweden)

    George Livadiotis


    Full Text Available The kappa distributions, or their equivalent, the q-exponential distributions, are the natural generalization of the classical Boltzmann-Maxwell distributions, applied to the study of the particle populations in collisionless space plasmas. A huge step in the development of the theory of kappa distributions and their applications in space plasma physics has been achieved with the discovery that the observed kappa distributions are connected with the solid statistical background of non-extensive statistical mechanics. Now that the statistical framework has been identified, it is straightforward to improve our understanding of the nature of the kappa index (or the entropic q-index that governs these distributions. One critical topic is the dependence of the kappa index on the degrees of freedom. In this paper, we first show how this specific dependence is naturally emerged, using the formalism of the N-particle kappa distribution of velocities. Then, the result is extended in the presence of potential energies. It is shown that the kappa index is simply related to the kinetic and potential degrees of freedom. In addition, it is shown that various problems of non-extensive statistical mechanics, such as (i the correlation dependence on the total number of particles; and (ii the normalization divergence for finite kappa indices, are resolved considering the kappa index dependence on the degrees of freedom.

  4. Kappa-Deformations: Historical Developments and Recent Results

    CERN Document Server

    Lukierski, Jerzy


    I shall recall in historical perspective some results from nineties and show further how $\\kappa$-deformed symmetries and $\\kappa$-Minkowski space inspired DSR (Doubly of Deformed Special Relativity) approach proposed after 2000. As very recent development I shall show how to describe quantum-covariant $\\kappa$-deformed phase spaces by passing from Hopf algebras to Hopf algebroids (arXiv:1507.02612) and I will briefly describe the $\\kappa$-deformations of $AdS_5 \\times S^5$ superstring target spaces (arXiv:1510.030.83).

  5. Imaging and Spectroscopic Observations of a Transient Coronal Loop: Evidence for the Non-Maxwellian $\\kappa$-Distributions

    CERN Document Server

    Dudik, Jaroslav; Dzifcakova, Elena; Del Zanna, Giulio; Williams, David R; Karlicky, Marian; Mason, Helen E; Lorincik, Juraj; Kotrc, Pavel; Farnik, Frantisek; Zemanova, Alena


    We report on the SDO/AIA and Hinode/EIS observations of a transient coronal loop. The loop brightens up in the same location after the disappearance of an arcade formed during a B8.9-class microflare three hours earlier. EIS captures this loop during its brightening phase as observed in most of the AIA filters. We use the AIA data to study the evolution of the loop, as well as to perform the DEM diagnostics as a function of $\\kappa$. Fe XI--XIII lines observed by EIS are used to perform the diagnostics of electron density and subsequently the diagnostics of $\\kappa$. Using ratios involving the Fe XI 257.772\\AA selfblend, we diagnose $\\kappa$ $\\lesssim$ 2, i.e., an extremely non-Maxwellian distribution. Using the predicted Fe line intensities derived from the DEMs as a function of $\\kappa$, we show that, with decreasing $\\kappa$, all combinations of ratios of line intensities converge to the observed values, confirming the diagnosed $\\kappa$ $\\lesssim$ 2. These results represent the first positive diagnostics ...

  6. Critical current densities and n-values of MgB2 strands over a wide range of temperatures and fields (United States)

    Li, G. Z.; Yang, Y.; Susner, M. A.; Sumption, M. D.; Collings, E. W.


    Transport measurements of critical current density, Jct, in monocore powder-in-tube MgB2 strands have been carried out at temperatures, T, of from 4.2 to 40 K, and in transverse fields, B, of up to 14 T. Processing methods used were conventional continuous tube forming/filling (CTFF) and internal magnesium diffusion (IMD). Strands with several powder compositions were measured, including binary (undoped) MgB2, 2% carbon doped MgB2, and 3% carbon doped MgB2. Magnetization loops (M-B) were also measured, and magnetic critical current density, Jcm, values extracted from them. The transport, Jct(B) and magnetic, Jcm(B), critical current densities were compared. Also studied was the influence of doping on the resistively measured irreversibility field, Birr, and upper critical field, Bc2. Critical current densities, Jct, and n-values were extracted from transport measurements and were found to be universally related (for all B and T) according to n\\propto {J}_{{ct}}^{m} in which m = 0.52 ± 0.11. Likewise n was found to be related to B according to n ∝ B-p with a T-dependent p in the range of about 0.08-0.21. Further analysis of the field (B) and temperature (T) dependences of n-value resulted in an expression that enabled n(B,T), for all B and T, to be estimated for a given strand based on the results of transport Jct(B) measurements made at one arbitrarily chosen temperature.

  7. Brane Effective Actions, Kappa-Symmetry and Applications

    Directory of Open Access Journals (Sweden)

    Joan Simón


    Full Text Available This is a review on brane effective actions, their symmetries and some of their applications. Its first part covers the Green–Schwarz formulation of single M- and D-brane effective actions focusing on kinematical aspects: the identification of their degrees of freedom, the importance of world volume diffeomorphisms and kappa symmetry to achieve manifest spacetime covariance and supersymmetry, and the explicit construction of such actions in arbitrary on-shell supergravity backgrounds. Its second part deals with applications. First, the use of kappa symmetry to determine supersymmetric world volume solitons. This includes their explicit construction in flat and curved backgrounds, their interpretation as Bogomol’nyi–Prasad–Sommerfield (BPS states carrying (topological charges in the supersymmetry algebra and the connection between supersymmetry and Hamiltonian BPS bounds. When available, I emphasise the use of these solitons as constituents in microscopic models of black holes. Second, the use of probe approximations to infer about the non-trivial dynamics of strongly-coupled gauge theories using the anti de Sitter/conformal field theory (AdS/CFT correspondence. This includes expectation values of Wilson loop operators, spectrum information and the general use of D-brane probes to approximate the dynamics of systems with small number of degrees of freedom interacting with larger systems allowing a dual gravitational description. Its final part briefly discusses effective actions for N D-branes and M2-branes. This includes both Super-Yang-Mills theories, their higher-order corrections and partial results in covariantising these couplings to curved backgrounds, and the more recent supersymmetric Chern–Simons matter theories describing M2-branes using field theory, brane constructions and 3-algebra considerations.

  8. Women in Leadership Roles in Phi Delta Kappa. (United States)

    Harder, Martha B.; And Others

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

  9. The scalar kappa from D+ -> K- pi+ pi+: Further Studies

    CERN Document Server

    Göbel, C


    We briefly review the recent results obtained by Fermilab experiment E791 on the Dalitz plot analysis of the decay D+ -> K- pi+ pi+, where indication for a light Kpi scalar resonance, the kappa, was found. We also present preliminary studies providing further information on the phase behavior of the scalar components at low mass, supporting the previous indication for the kappa.

  10. Origins and properties of kappa distributions in space plasmas (United States)

    Livadiotis, George


    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. Small-angle neutron scattering study on irradiated kappa carrageenan

    Energy Technology Data Exchange (ETDEWEB)

    Abad, Lucille [Neutron Science Laboratory, Institute for Solid State Physics, University of Tokyo, 106-1 Shirakata, Tokai, Ibaraki 319-1106 (Japan) and Philippine Nuclear Research Institute, Commonwealth Ave., Diliman, Quezon City (Philippines) and Advanced Science Research Center, Japan Atomic Energy Research Institute, 2-4 Shirane Shirakata, Tokai, Ibaraki 319-1195 (Japan)]. E-mail:; Okabe, Satoshi [Neutron Science Laboratory, Institute for Solid State Physics, University of Tokyo, 106-1 Shirakata, Tokai, Ibaraki 319-1106 (Japan); Koizumi, Satoshi [Advanced Science Research Center, Japan Atomic Energy Research Institute, 2-4 Shirane Shirakata, Tokai, Ibaraki 319-1195 (Japan); Shibayama, Mitsuhiro [Neutron Science Laboratory, Institute for Solid State Physics, University of Tokyo, 106-1 Shirakata, Tokai, Ibaraki 319-1106 (Japan)]. E-mail:


    The structure of gamma-ray-irradiated {kappa}-carrageenan in aqueous solutions was investigated in terms of small-angle neutron scattering. The scattered intensity, I(q), of non-irradiated {kappa}-carrageenan solutions (5 wt%) was well described with an Ornstein-Zernike (OZ)-type function with the correlation length of 85 A, indicating that the {kappa}-carrageenan solution behaves just as a polymer solution in the semi-dilute regime. By increasing the irradiation dose (100 kGy), I(q) changed to a power-law function with the scattering exponent of -1.84. Further increase in dose results in a recovery of OZ-type function. This indicates that a progressive cleavage of {kappa}-carrageenan chains takes place randomly, leading to a self-similar structure at 100 kGy. This is followed by further segmentation of {kappa}-carrageenan chains.

  12. AGRO100 inhibits activation of nuclear factor-kappaB (NF-kappaB) by forming a complex with NF-kappaB essential modulator (NEMO) and nucleolin. (United States)

    Girvan, Allicia C; Teng, Yun; Casson, Lavona K; Thomas, Shelia D; Jüliger, Simone; Ball, Mark W; Klein, Jon B; Pierce, William M; Barve, Shirish S; Bates, Paula J


    AGRO100, also known as AS1411, is an experimental anticancer drug that recently entered human clinical trials. It is a member of a novel class of antiproliferative agents known as G-rich oligonucleotides (GRO), which are non-antisense, guanosine-rich phosphodiester oligodeoxynucleotides that form stable G-quadruplex structures. The biological activity of GROs results from their binding to specific cellular proteins as aptamers. One important target protein of GROs has been previously identified as nucleolin, a multifunctional protein expressed at high levels by cancer cells. Here, we report that AGRO100 also associates with nuclear factor-kappaB (NF-kappaB) essential modulator (NEMO), which is a regulatory subunit of the inhibitor of kappaB (IkappaB) kinase (IKK) complex, and also called IKKgamma. In the classic NF-kappaB pathway, the IKK complex is required for phosphorylation of IkappaBalpha and subsequent activation of the transcription factor NF-kappaB. We found that treatment of cancer cells with AGRO100 inhibits IKK activity and reduces phosphorylation of IkappaBalpha in response to tumor necrosis factor-alpha stimulation. Using a reporter gene assay, we showed that AGRO100 blocks both tumor necrosis factor-alpha-induced and constitutive NF-kappaB activity in human cancer cell lines derived from cervical, prostate, breast, and lung carcinomas. In addition, we showed that, in AGRO100-treated cancer cells, NEMO is coprecipitated by nucleolin, indicating that both proteins are present in the same complex. Our studies suggest that abrogation of NF-kappaB activity may contribute to the anticancer effects of AGRO100 and that nucleolin may play a previously unknown role in regulating the NF-kappaB pathway.

  13. Combined detection of α-fetoprotein and free β-human chorionic gonadotropin in screening for trisomy 21 and management of cases in the moderate risk value range. (United States)

    Li, Yahong; Zhang, Xiaojuan; Sun, Yun; Hong, Dongyang; Wang, Yanyun; Xu, Zhengfeng; Jiang, Tao


    Down syndrome is the most common cause of prenatal chromosomal abnormalities, and prenatal serum screening is an effective method for decreasing the birth prevalence of children with Down syndrome. The aim of the present study was to observe the effect of duplex screening and investigate the treatment of cases under specific conditions. The medians of free β-human chorionic gonadotropin (HCG) and α-fetoprotein (AFP) were calculated and compared with those embedded in the 2T software. The detection and false-positive rates were analyzed under different conditions, and the distribution of Down syndrome cases was investigated in different risk ranges. Finally, suitable recommendations for further diagnostic investigation were provided according to the status of each individual. The medians of free β-HCG and AFP were found to differ from the corresponding medians embedded in the 2T software (P<0.01), and on the basis of a 5% false-positive rate, the detection rate would increase from 63.6 to 67.8% when compared with medians embedded in the 2T software, indicating we should establish our own medians of free β-HCG and AFP. In addition, residual cases (risk value <1/300) with relevant Down syndrome indications mainly concentrated at risk values between 1/1,000 and 1/300, and partial residual screening cases were verified through diverse methods. These findings indicated that different laboratories should establish their own medians; furthermore, what is classed as moderate risk is extremely important in screening for Down syndrome and reasonable recommendations may be offered under different conditions.

  14. Kinetic study of ion acoustic twisted waves with kappa distributed electrons (United States)

    Arshad, Kashif; Aman-ur-Rehman, Mahmood, Shahzad


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

  15. Energetic Particle Spectral Shapes in Planetary Magnetospheres; Assessment of the Kappa Function (United States)

    Mauk, B.


    In assessing the efficacy of the kappa distribution function in space environments, it is useful to follow two paths. First, to what extent do we consider the kappa function (or any function) to represent some kind of universal spectral shape that indicates common physical processes occurring in a wide diversity of space environments? Second, how useful is the kappa function in quantitatively characterizing observed spectral shapes, particularly for the purpose permitting further quantitative analyses of the environment (e. g. wave growth). In this report I evaluate the efficacy of the kappa distribution in representing energetic particle spectral shapes in planetary magnetospheres from both perspectives. In particular, I expand on the extensive treatment provided by Carbary et al. (2014) by taking a more explicit comparative approach between the different planets (Earth, Jupiter, Saturn, Uranus, and Neptune) and also focusing on the most intense (and therefore from my perspective the most interesting) spectra within each of these different planets. There is no question that the "power law tail" represents as close to a universal characteristic of planetary space environments as one could hope to find. Such a universal shape must represent some universality in the energization and/or equilibrating processes. Also, there is no question that such tails must (to be non-divergent) and do roll over to flatter shapes at lower energies. In a number of applications, this basic characteristic has been usefully characterized by the kappa function to extract such parameters of the system as flow velocities. However, at least for the more intense spectra at Earth, Jupiter, Saturn, and Uranus, the kappa function in fact does a relatively poor job in representing the low energy roll-over of energetic particle spectra. Other functional forms have been found to be much more useful for characterizing these spectral shapes over a broad range of energies. And specifically, a very

  16. B cell development in mice that lack one or both immunoglobulin kappa light chain genes.


    J. Chen(Florida State University, Tallahassee, U.S.A.); Trounstine, M; Kurahara, C.; Young, F.; Kuo, C C; Y. Xu; Loring, J.F.; Alt, F W; Huszar, D


    We have generated mice that lack the ability to produce immunoglobulin (Ig) kappa light chains by targeted deletion of J kappa and C kappa gene segments and the intervening sequences in mouse embryonic stem cells. In wild type mice, approximately 95% of B cells express kappa light chains and only approximately 5% express lambda light chains. Mice heterozygous for the J kappa C kappa deletion have approximately 2-fold more lambda+ B cells than wild-type littermates. Compared with normal mice, ...

  17. The Nuclear Factor kappaB Pathway: A Link to the Immune System in the Radiation Response (United States)

    Hellweg, Christine; Baumstark-Khan, Christa; Reitz, Guenther; Chishti, Arif Ali; Koch, Kristina; Manchanda, Kashish

    Understanding the cellular radiation response is an essential prerequisite for the risk assessment of astronauts’ space radiation exposure during long-term space missions and for effective countermeasure development. In addition to the space radiation effects, other environmental factors during space missions such as microgravity have profound effects on the body, e.g. suppression of the innate and acquired immune response. Exposure to ionizing radiation modulates immune responses in a complex dose-dependent pattern, with possible anti-inflammatory effects in the low dose range, expression of pro-inflammatory cytokines at moderate doses and immunosuppression after exposure to higher doses due to precursor cell death together with concomitant exacerbated innate immune responses. A central regulator in the immune system is the transcription factor Nuclear Factor kB (NF-kappaB). In this work, the role of NF-kappaB in the cellular response to space relevant radiation qualities was analyzed. It was shown with a recombinant human NF-kappaB reporter cell line that heavy ions with a linear energy transfer (LET) of 100-300 keV/µm have a nine times higher potential to activate the NF-kappaB pathway compared to X-rays (150 kV). ATM was essential for NF-kappaB activation in response to X-rays and heavy ions. Knockdown of the NF-kappaB subunit RelA (p65) resulted in higher sensitivity towards X-rays. Reverse Transcriptase real-time quantitative PCR (RT-qPCR) experiments showed that after exposure to radiation, NF-kappaB predominantly upregulates genes involved in intercellular communication processes, especially genes coding for chemokines, suggesting an important contribution of NF-kappaB in the molecular profile of the reaction to radiation, which can comprise features of inflammation and wound healing processes. This is process is strictly NF-kappaB dependent as this response is completely absent in RelA knockdown cells. These results show that the role of NF-kappaB in

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

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

  19. Radio-isotopic assays of vitamin B12: interest of Kappa index in a multicentric study. Dosages radio-isotopiques de la vitamine B12: interet du test Kappa dans une evaluation multicentrique

    Energy Technology Data Exchange (ETDEWEB)

    Fourre, C. (Hopital de Bicetre, 94 - le Kremlin-Bicetre (France)); Guiraud-Vitaux, F. (Hopital de Montfermeil, 93 (France)); Labriolle-Vaylet, C. de (Hopital Saint-Antoine, 75 - Paris (France)); Colas-Linhart, N. (Hopital Beaujon, 92 - Clichy (France))


    Owing to the lack of a reference technique and of an international cobalamin (vitamin B12) standard, and the large discrepancy between laboratory norms, the authors performed a multicentric study to compare five RIA kits usually used. First, classical tests were used to evaluate the analytical performances of each kit. Results did not demonstrate any superiority of one kit over another. Secondly, B12 values were classified among three categories (low, normal and high) characterized by laboratory and then manufacturer norms. The concordance between these two ''judgments'' was evaluated with the Kappa coefficient. In addition, the Kappa index proved that the norms supplied by the manufacturer were better than those of laboratories. But mean Kappa coefficient established for each norm gave us an insatisfactory result. Third, clinical informations allowed to improve the classification of the patients. New limits were defined for each technique and should be tested further, routinely in each laboratory. (author).

  20. D3 dopamine and kappa opioid receptor alterations in human brain of cocaine-overdose victims. (United States)

    Mash, D C; Staley, J K


    Cocaine is thought to be addictive because chronic use leads to molecular adaptations within the mesolimbic dopamine (DA) circuitry, which affects motivated behavior and emotion. Although the reinforcing effects of cocaine are mediated primarily by blockade of DA uptake, reciprocal signaling between DA and endogenous opioids has important implications for understanding cocaine dependence. We have used in vitro autoradiography and ligand binding to map D3 DA and kappa opioid receptors in the human brains of cocaine-overdose victims. The number of D3 binding sites was increased one-to threefold over the nucleus accumbens and ventromedial sectors of the caudate and putamen from cocaine-overdose victims, as compared to age-matched and drug-free control subjects. D3 receptor/cyclophilin mRNA ratios in the nucleus accumbens were increased sixfold in cocaine-overdose victims over control values, suggesting that cocaine exposure also affects the expression of D3 receptor mRNA. The number of kappa opioid receptors in the nucleus accumbens and other corticolimbic areas from cocaine fatalities was increased twofold as compared to control values. Cocaine-overdose victims exhibiting preterminal excited delirium had a selective upregulation of kappa receptors measured also in the amygdala. Understanding the complex regulatory profiles of DA and opioid synaptic markers that occur with chronic misuse of cocaine may suggest multitarget strategies for treating cocaine dependence.

  1. The mu1, mu2, delta, kappa opioid receptor binding profiles of methadone stereoisomers and morphine

    DEFF Research Database (Denmark)

    Kristensen, K; Christensen, C B; Christrup, Lona Louring


    The binding affinities of racemic methadone and its optical isomers R-methadone and S-methadone were evaluated for the opioid receptors mu1, mu2, delta and kappa, in comparison with that of morphine. The analgesic R-methadone had a 10-fold higher affinity for mu1 receptors than S-methadone (IC50 3.......0 nM and 26.4 nM, respectively). At the mu2 receptor, the IC50 value of R-methadone was 6.9 nM and 88 nM for S-methadone, respectively. As expected, R-methadone had twice the affinity for mu1 and mu2 receptors than the racemate. All of the compounds tested had low affinity for the delta and kappa...


    Institute of Scientific and Technical Information of China (English)

    Yongjian Xu; Xinping Li; Meiyun Zhang


    The effect of washing temperature, washing stages and the cooking operation on the ethanol pulp had been investigated, and the reason for higher kappa number of the ethanol pulp was discussed. The results preliminarily showed that the dissolved lignin could re-adsorb to fiber surface by means of fiber classification technology and explained the questions found during the study. Some measures were taken to reduce the kappa number, the results had shown that there was obvious absorption in the ethanol pulping;lignin remained in the pulp could easily be dissolved and the pulp with lower kappa number could be obtained at a higher temperature; the kappa number could reduce by increasing washing time; it could enable dissolved lignin to separate out from the ethanol pulp and restrain the lignin absorption by blowing cooking liquid at high temperature.

  3. The effects of a kappa-distribution in the heliosheath on the global heliosphere and ENA flux at 1 AU

    CERN Document Server

    Heerikhuisen, J; Florinski, V; Zank, G P; Roux, J A le


    We investigate heliosheath energetic neutral atom (ENA) fluxes at keV energies, by assuming that the heliosheath proton distribution can be approximated by a kappa-distribution. The choice of the kappa parameter derives from observational data of the solar wind (SW). This has direct applications to the upcoming IBEX mission. We will look at all-sky ENA maps within the IBEX energy range (10 eV to 6 keV), as well as ENA energy spectra in several directions. We find that the use of kappa, as opposed to a Maxwellian, gives rise to greatly increased ENA fluxes above 1 keV, while medium energy fluxes are somewhat reduced. We show how IBEX data can be used to estimate the spectral slope in the heliosheath, and that the use of kappa reduces the differences between ENA maps at different energies. We also investigate the effect introducing a kappa-distribution has on the global interaction between the SW and the local interstellar medium (LISM), and find that there is generally an increase in energy transport from the ...

  4. Genomic structure and expression analysis of the RNase kappa family ortholog gene in the insect Ceratitis capitata. (United States)

    Rampias, Theodoros N; Fragoulis, Emmanuel G; Sideris, Diamantis C


    Cc RNase is the founding member of the recently identified RNase kappa family, which is represented by a single ortholog in a wide range of animal taxonomic groups. Although the precise biological role of this protein is still unknown, it has been shown that the recombinant proteins isolated so far from the insect Ceratitis capitata and from human exhibit ribonucleolytic activity. In this work, we report the genomic organization and molecular evolution of the RNase kappa gene from various animal species, as well as expression analysis of the ortholog gene in C. capitata. The high degree of amino acid sequence similarity, in combination with the fact that exon sizes and intronic positions are extremely conserved among RNase kappa orthologs in 15 diverse genomes from sea anemone to human, imply a very significant biological function for this enzyme. In C. capitata, two forms of RNase kappa mRNA (0.9 and 1.5 kb) with various lengths of 3' UTR were identified as alternative products of a single gene, resulting from the use of different polyadenylation signals. Both transcripts are expressed in all insect tissues and developmental stages. Sequence analysis of the extended region of the longer transcript revealed the existence of three mRNA instability motifs (AUUUA) and five poly(U) tracts, whose functional importance in RNase kappa mRNA decay remains to be explored.

  5. Electromagnetic ion-cyclotron instability in a dusty plasma with product-bi-kappa distributions for the plasma particles

    CERN Document Server

    Santos, Michel S dos; Gaelzer, Rudi


    We study the dispersion relation for parallel propagating ion-cyclotron (IC) waves in a dusty plasma, considering that ions and electrons may be represented by product-bi-kappa (PBK) velocity distributions. The results obtained by numerical solution of the dispersion relation, in a case with isotropic Maxwellian distributions for electrons and PBK distribution for ions, show the occurrence of the electromagnetic ion-cyclotron instability (EMIC), and show that the decrease in the kappa indexes of the PBK ion distribution leads to significant increase of the instability, in magnitude of the growth rates and in range in wavenumber space. On the other hand, for anisotropic Maxwellian distribution for ions and PBK distribution for electrons, the decrease of the kappa index in the PBK electron distribution contributes to reduce the EMIC instability, but the reduction effect is much less pronounced than that obtained with the same combination of distributions in the case of the ion-firehose instability, shown in a r...

  6. On kappa-deformed D=4 quantum conformal group

    CERN Document Server

    Kosi'nski, P; Maslanka, P


    This paper is presented on the occasion of 60-th birthday of Jose Adolfo de Azcarraga who in his very rich scientific curriculum vitae has also a chapter devoted to studies of quantum-deformed symmetries, in particular deformations of relativistic and Galilean space-time symmetries [1-4]. In this paper we provide new steps toward describing the $\\kappa$-deformed D=4 conformal group transformations. We consider the quantization of D=4 conformal group with dimensionful deformation parameter $\\kappa$. Firstly we discuss the noncommutativity following from the Lie-Poisson structure described by the light-cone $\\kappa$-Poincar\\'{e} $r$-matrix. We present complete set of D=4 conformal Lie-Poisson brackets and discuss their quantization. Further we define the light-cone $\\kappa$-Poincar\\'{e} quantum $R$-matrix in O(4,2) vector representation and discuss the inclusion of noncommutative conformal translations into the framework of $\\kappa$-deformed conformal quantum group. The problem with real structure of $\\kappa$-d...

  7. Kappa Opioids, Salvinorin A and Major Depressive Disorder. (United States)

    Taylor, George T; Manzella, Francesca


    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.

  8. Diarctigenin, a lignan constituent from Arctium lappa, down-regulated zymosan-induced transcription of inflammatory genes through suppression of DNA binding ability of nuclear factor-kappaB in macrophages. (United States)

    Kim, Byung Hak; Hong, Seong Su; Kwon, Soon Woo; Lee, Hwa Young; Sung, Hyeran; Lee, In-Jeong; Hwang, Bang Yeon; Song, Sukgil; Lee, Chong-Kil; Chung, Daehyun; Ahn, Byeongwoo; Nam, Sang-Yoon; Han, Sang-Bae; Kim, Youngsoo


    Diarctigenin was previously isolated as an inhibitor of nitric oxide (NO) production in macrophages from the seeds of Arctium lappa used as an alternative medicine for the treatment of inflammatory disorders. However, little is known about the molecular basis of these effects. Here, we demonstrated that diarctigenin inhibited the production of NO, prostaglandin E(2), tumor necrosis factor-alpha, and interleukin (IL)-1beta and IL-6 with IC(50) values of 6 to 12 miciroM in zymosan- or lipopolysaccharide-(LPS) activated macrophages. Diarctigenin attenuated zymosan-induced mRNA synthesis of inducible NO synthase (iNOS) and also inhibited promoter activities of iNOS and cytokine genes in the cells. Because nuclear factor (NF)-kappaB plays a pivotal role in inflammatory gene transcription, we next investigated the effect of diarctigenin on NF-kappaB activation. Diarctigenin inhibited the transcriptional activity and DNA binding ability of NF-kappaB in zymosan-activated macrophages but did not affect the degradation and phosphorylation of inhibitory kappaB (IkappaB) proteins. Moreover, diarctigenin suppressed expression vector NF-kappaB p65-elicited NF-kappaB activation and also iNOS promoter activity, indicating that the compound could directly target an NF-kappa-activating signal cascade downstream of IkappaB degradation and inhibit NF-kappaB-regulated iNOS expression. Diarctigenin also inhibited the in vitro DNA binding ability of NF-kappaB but did not affect the nuclear import of NF-kappaB p65 in the cells. Taken together, diarctigenin down-regulated zymosan- or LPS-induced inflammatory gene transcription in macrophages, which was due to direct inhibition of the DNA binding ability of NF-kappaB. Finally, this study provides a pharmacological potential of diarctigenin in the NF-kappaB-associated inflammatory disorders.

  9. Structure-activity relationship studies of chalcone leading to 3-hydroxy-4,3',4',5'-tetramethoxychalcone and its analogues as potent nuclear factor kappaB inhibitors and their anticancer activities. (United States)

    Srinivasan, Balasubramanian; Johnson, Thomas E; Lad, Rahul; Xing, Chengguo


    Chalcone is a privileged structure, demonstrating promising anti-inflammatory and anticancer activities. One potential mechanism is to suppress nuclear factor kappa B (NF-kappaB) activation. The structures of chalcone-based NF-kappaB inhibitors vary significantly that there is minimum information about their structure-activity relationships (SAR). This study aims to establish SAR of chalcone-based compounds to NF-kappaB inhibition, to explore the feasibility of developing simple chalcone-based potent NF-kappaB inhibitors, and to evaluate their anticancer activities. Three series of chalcones were synthesized in one to three steps with the key step being aldol condensation. These candidates demonstrated a wide range of NF-kappaB inhibitory activities, some of low micromolar potency, establishing that structural complexity is not required for NF-kappaB inhibition. Lead compounds also demonstrate potent cytotoxicity against lung cancer cells. Their cytotoxicities correlate moderately well with their NF-kappaB inhibitory activities, suggesting that suppressing NF-kappaB activation is likely responsible for at least some of the cytotoxicities. One lead compound effectively inhibits lung tumor growth with no signs of adverse side effects.

  10. Evidence for {Kappa}{sup +} {r_arrow} {pi}{sup +}{nu}{anti {nu}}

    Energy Technology Data Exchange (ETDEWEB)

    Kettell, S.


    The first observation of the decay {Kappa}{sup +} {r_arrow} {pi}{sup +}{nu}{anti {nu}} has been reported. The E787 experiment presented evidence for the {Kappa}{sup +} {r_arrow} {pi}{sup +}{nu}{anti {nu}} decay, based on the observation of a single clean event from data collected during the 1995 run of the AGS (Alternating Gradient Synchrotron at Brookhaven National Laboratory). The branching ratio indicated by this observation, {Beta}({Kappa}{sup +} {r_arrow} {pi}{sup +}{nu}{anti {nu}}) = 4.2{sub {minus}3.5}{sup +9.7} {times} 10{sup {minus}10}, is consistent with the Standard Model expectation although the central experimental value is four times larger. The final E787 data sample, from the 1995--98 runs, should reach a sensitivity of about five times that of the 1995 run alone. A new experiment, E949, has been given scientific approval and should start data collection in 2001. It is expected to achieve a sensitivity of more than an order of magnitude below the prediction of the Standard Model.

  11. Profil Antioksidan Darah Tikus Diabetes dengan Asupan Beras Merah yang Diperkaya Kappa-Karagenan dan Ekstrak Antosianin

    Directory of Open Access Journals (Sweden)

    Nurhidajah Nurhidajah


    Full Text Available This study aimed to analyze the effect of red rice enriched-kappa-carrageenan and anthocyanin extracts on blood antioxidant profile in diabetic rats. Variables analyzed in this research were blood glucose, malondialdehyde (MDA level, and plasma antioxidant by Ferric Reducing Ability of Plasma (FRAP method. This study was conducted in vivo on male Wistar rats aged 2.5 months using completely randomized design. Rats divided into 6 groups based on types of feed, standard feed (normal and DM, red rice (BM, red rice enriched kappa-carrageenan (BMK, red rice enriched extracts of anthocyanin (BMA and red rice enriched with kappa-carrageenan and extract anthocyanin (BMKA. Experiments were carried out for 6 weeks. Rats feed with red rice showed decreased in blood glucose levels from 234.26 to 84.78 mg/dL (p = 0.000, MDA diabetic group compared to BMKA 2.175 and 0.530 μmol/L (p = 0.000 respectively, and the rate of FRAP in DM and BMKA 69 and 216 nmol/mL (p = 0.000 respectively. This study showed that red rice enriched with kappa-carrageenan and anthocyanin extract was able to decrease blood glucose levels and increase plasma antioxidant of diabetic rats which characterized by decreased MDA value and increased FRAP value.   ABSTRAK Penelitian ini bertujuan mengkaji pengaruh pemberian beras merah yang diperkaya kappa-karagenan dan ekstrak antosianin terhadap profil antioksidan darah pada tikus Diabetes Melitus (DM. Indikator penelitian adalah penurunan glukosa darah dan angka Malondialdehid (MDA serta peningkatan antioksidan plasma dengan metode Ferric Reducing Ability of Plasma (FRAP. Penelitian ini dilakukan secara in vivo pada hewan coba tikus Wistar usia 2,5 bulan dengan desain penelitian rancangan acak lengkap (RAL. Tikus dibagi 6 kelompok pakan, yaitu standar negatif dan positif (normal dan DM, beras merah (BM, beras merah ditambah kappa-karagenan (BMK, beras merah ditambah ekstrak antosianin (BMA, dan beras merah ditambah kappa-karagenan dan

  12. Proton Cyclotron Instability Threshold Condition of Suprathermal Protons by Kappa Distribution

    Institute of Scientific and Technical Information of China (English)

    XIAO Fuliang; ZHOU Qinghua; HE Huiyong; TANG Lijun; FANG Jiayuan


    Observation has clearly shown that natural space plasmas generally possess a pronounced non-Maxwellian high-energy tail distribution that can be well modeled by a kappa distribution. In this study we investigate the proton cyclotron wave instability driven by the temperature anisotropy (T⊥/T||>1) of suprathermal protons modeled with a typical kappa distribution in the magnetosheath. It is found that as in the case for a regular bi-Maxwellian, the suprathermal proton temperature anisotropy is subject to the threshold condition of this proton cyclotron instability and the instability threshold condition satisfies a general form T⊥/T|| - 1 = S/βα||, with a very narrow range of the fitting parameters: 0.40 ≤ α ≤ 0.45, and a relatively sensitive variation 0.27 ≤ S ≤ 0.65, over 0.01 < β|| < 10. Furthermore, the difference in threshold conditions between the kappa distribution and the bi-Maxwellian distribution is found to be small for a relatively strong growth but becomes relatively obvious for a weak wave growth. The results may provide a deeper insight into the physics of this instability threshold for the proton cyclotron waves.

  13. Light scattering studies of irradiated {kappa}- and {iota}-carrageenan

    Energy Technology Data Exchange (ETDEWEB)

    Abad, L.V. [Neutron Science Laboratory, Institute for Solid State Physics, University of Tokyo, 106-1 Shirakata, Tokai, Ibaraki 319-1106 (Japan) and Philippine Nuclear Research Institute, Commonwealth Ave., Diliman, Quezon City (Philippines)]. E-mail:; Nasimova, I.R. [Neutron Science Laboratory, Institute for Solid State Physics, University of Tokyo, 106-1 Shirakata, Tokai, Ibaraki 319-1106 (Japan); Physics Department, Moscow State University, Moscow 119992 (Russian Federation); Aranilla, C.T. [Philippine Nuclear Research Institute, Commonwealth Ave., Diliman, Quezon City (Philippines); Shibayama, M. [Neutron Science Laboratory, Institute for Solid State Physics, University of Tokyo, 106-1 Shirakata, Tokai, Ibaraki 319-1106 (Japan)]. E-mail:


    The relationships between the molecular weight (Mw) and the characteristic decay time distribution function G({gamma}) of irradiated kappa ({kappa}-) and iota ({iota}-) carrageenan were studied by static and dynamic light scattering (DLS). Mw and the characteristic decay time ({gamma}{sup -1}) are both steep decreasing exponential function with radiation dose. The dynamic behavior of irradiated {iota}-carrageenan was compared to irradiated {kappa}-carrageenan by DLS. The intensity correlation function of both carrageenans shifted towards shorter relaxation times with increasing radiation dose. Irradiated {iota}-carrageenan like {kappa}-carrageenan exhibits power law behavior at 0-50 kGy (at 0.05-0.1M KCl) indicating similar gelation behaviors. The temperature at which transition from coil to helix takes place (conformational transition temperature) decreases with increasing irradiation dose. A new faster relaxation mode appears at around 0.1-1 ms for both carrageenans between 100 and 150 kGy. Maximum peak height for this mode is at 100 kGy which corresponds to the optimum biological activity of {kappa}- and {iota}-carrageenan.

  14. 40 CFR 600.314-08 - Updating label values, annual fuel cost, Gas Guzzler Tax, and range of fuel economy for... (United States)


    ... cost, Gas Guzzler Tax, and range of fuel economy for comparable automobiles. 600.314-08 Section 600.314-08 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) ENERGY POLICY FUEL ECONOMY AND CARBON-RELATED EXHAUST EMISSIONS OF MOTOR VEHICLES Fuel Economy Regulations for 1977 and...

  15. KAPPA GOLF继续时尚活力

    Institute of Scientific and Technical Information of China (English)


    中国动向(集团)有限公司旗下的Kappa GOLF作为高尔夫运动服装领军品牌再次成为2012年汇丰冠军赛唯一服装合作伙伴。中国动向集团董事长陈义作为代表参加了汇丰冠军赛的职业业余配对赛。Kappa GOLF与世锦赛-汇丰冠军赛的合作进入第四年,本届赛事,Kappa GOLF为所有赛事官员、裁判、贵宾、志愿者提供专用


    Institute of Scientific and Technical Information of China (English)

    YongjianXu; XinpingLi; MeiyunZhang


    The effect of washing temperature, washing stagesand the cooking operation on the ethanol pulp hadbeen investigated, and the reason for higher kappanumber of the ethanol pulp was discussed. Theresults preliminarily showed that the dissolved lignincould re-adsorb to fiber surface by means of fiberclassification technology and explained the questionsfound during the study. Some measures were taken toreduce the kappa number, the results had shown thatthere was obvious absorption in the ethanol pulping;lignin remained in the pulp could easily be dissolvedand the pulp with lower kappa number could beobtained at a higher temperature; the kappa numbercould reduce by increasing washing time; it couldenable dissolved lignin to separate out fi'om theethanol pulp and restrain the lignin absorption byblowing cooking liquid at high temperature.

  17. Quantum Measurements and the kappa--Poincare Group

    CERN Document Server

    Camacho, A; Camacho, Abel


    The possible description of the vacuum of quantum gravity through the so called kappa--Poincare group is analyzed considering some of the consequences of this symmetry in the path integral formulation of nonrelativistic quantum theory. This study is carried out with two cases, firstly, a free particle, and finally, the situation of a particle immersed in a homogeneous gravitational field. It will be shown that the kappa--Poincare group implies the loss of some of the basic properties associated to Feynman's path integral. For instance, loss of the group characteristic related to the time dependence of the evolution operator, or the breakdown of the composition law for amplitudes of events occurring successively in time. Additionally some similarities between the present idea and the so called restricted path integral formalism will be underlined. These analogies advocate the claim that if the kappa--Poincare group contains some of the physical information of the quantum gravity vacuum, then this vacuum could ...

  18. A nonextensive entropy approach to kappa-distributions

    CERN Document Server

    Leubner, M P


    Most astrophysical plasmas are observed to have velocity distribution functions exhibiting non-Maxwellian suprathermal tails. The high energy particle populations are accurately represented by the family of kappa-distributions where the use of these distributions has been unjustly criticized because of a perceived lack of theoretical justification. We show that distributions very close to kappa-distributions are a consequence of the generalized entropy favored by nonextensive statistics, which provides the missing link for power-law models of non-thermal features from fundamental physics. With regard to the the physical basis supplied by the Tsallis nonextensive entropy formalism we propose that this slightly modified functional form, qualitatively similar to the traditional kappa-distribution, be used in fitting particle spectra in the future.

  19. Assessing agreement with multiple raters on correlated kappa statistics. (United States)

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


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

  20. 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

    DEFF Research Database (Denmark)

    Junge, Tina


    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...... 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 linear weighted kappa. The inconsistency in results when using different methods of kappa calculation demonstrated the linear weighted...

  1. The current-voltage relationship revisited: exact and approximate formulas with almost general validity for hot magnetospheric electrons for bi-Maxwellian and kappa distributions

    Directory of Open Access Journals (Sweden)

    P. Janhunen

    Full Text Available We derive the current-voltage relationship in the auroral region taking into account magnetospheric electrons for the bi-Maxwellian and kappa source plasma distribution functions. The current-voltage formulas have in principle been well known for a long time, but the kappa energy flux formulas have not appeared in the literature before. We give a unified treatment of the bi-Maxwellian and kappa distributions, correcting some errors in previous work. We give both exact results and two kinds of approximate formulas for the current density and the energy flux. The first approximation is almost generally valid and is practical to compute. The first approximation formulas are therefore suitable for use in simulations. In the second approximation we assume in addition that the thermal energy is small compared to the potential drop. This yields even simpler linear formulas which are suitable for many types of event studies and which have a more transparent physical interpretation than the first approximation formulas. We also show how it is possible to derive the first approximation formulas even for those distributions for which the exact results can not be computed analytically. The kappa field-aligned conductance value turns out always to be smaller than the corresponding Maxwellian conductance. We also verify that the obtained kappa current density and energy flux formulas go to Maxwellian results when κ→∞.

    Key words. Current-voltage relationship · Bi-Maxwellian distributions · Kappa distribution

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

    CERN Document Server

    Gaelzer, Rudi; Meneses, Anelise Ramires


    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.

  3. The Present Status on sigma and kappa Meson Properties

    CERN Document Server

    Ishida, M


    The recent experimental data of both pipi / Kpi scattering and production processes, suggesting the existence of scalar sigma and kappa mesons, are reviewed. In many pipi /Kpi production processes the direct effects of their productions are observed, while they are, because of chiral symmetry, hidden in scattering processes, and now sigma(500--600) and kappa(800--900) are considered to be confirmed experimentally. The recent criticism on our method of analyses, which is based on the long believed prejudice of universal pipi / Kpi phase through scattering and production amplitudes, is explained not to be valid.

  4. Regularization of Kepler Problem in $\\kappa$-spacetime

    CERN Document Server

    Guha, Partha; S., Zuhair N


    In this paper we regularize the Kepler problem on $\\kappa$-spacetime in several different ways. First, we perform a Moser-type regularization and then we proceed for the Ligon-Schaaf regularization to our problem. In particular, generalizing Heckman-de Laat (J. Symplectic Geom. 10, (2012), 463-473) in the noncommutative context we show that the Ligon-Schaaf regularization map follows from an adaptation of the Moser regularization can be generalized to the Kepler problem on $\\kappa$-spacetime.

  5. Method for rapidly determining a pulp kappa number using spectrophotometry (United States)

    Chai, Xin-Sheng; Zhu, Jun Yong


    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.

  6. Localization of nuclear factor-kappa B (NF kappa B) and inhibitory factor-kappa B (I kappa B) in human fetal membranes and decidua at term and preterm delivery. (United States)

    Yan, X; Sun, M; Gibb, W


    The human fetal membranes and decidua are thought to be involved in the onset of human parturition. These tissues produce and respond to various cytokines, which may be involved in preterm labour and possibly term labour. They also show increasing production of prostaglandins (PGs) with advancing gestation and labour. The expression of PGHS-2, a rate limiting enzyme in PG synthesis, is increased in the fetal membranes at labour. The gene for PGHS-2 and many of the cytokine genes (e.g. TNFalpha, IL-1, IL-6) are stimulated by the transcription factor NF kappa B. This factor is composed of two subunits, p50 and p65, which are localized in the cytoplasm bound to I kappa B. When activated I kappa B is metabolized, and p50, p65 translocate to the nucleus to activate various genes. The purpose of the present study was to examine the tissue and cellular distribution of p65 and I kappa B in the human fetal membranes and decidua throughout gestation. Term tissues were obtained prior to labour by elective caesarean section (n=10) or following vaginal delivery (n=10) and 10 preterm tissues were obtained following labour prior to 37 weeks gestation. None of the tissues had any evidence of infection. The immunoreactive NF kappa B and I kappa B were localized in the tissues. p65 protein was found in the nucleus and cytoplasm of cells in the amnion, chorion laeve and decidua. In the amnion and chorion laeve, no changes occurred in subcellular localization with advancing gestation or term labour. However, in the decidua, there was a marked increase in the nuclear localization of i.r. p 65 in tissues obtained at term when compared with tissues delivered preterm. In the case of I kappa B, it was localized to the cytoplasm of cells in all tissues and there was an increase i.r. I kappa B in decidua at term compared to preterm but no change occurred in the amnion or chorion. The increase in nuclear localization of p65 in the decidua that occurs with advancing gestation, highlights the

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

    Energy Technology Data Exchange (ETDEWEB)

    Kesanakurti, Divya [Department of Plant Sciences, University of Hyderabad, Hyderabad (India); Sareddy, Gangadhara Reddy [Department of Bio-technology and Animal Sciences, University of Hyderabad, Hyderabad (India); Babu, Phanithi Prakash, E-mail: [Department of Bio-technology and Animal Sciences, University of Hyderabad, Hyderabad (India); Kirti, Pulugurtha Bharadwaja, E-mail: [Department of Plant Sciences, University of Hyderabad, Hyderabad (India)


    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.

  8. Dust-acoustic solitons in quantum plasma with kappa-distributed ions

    Indian Academy of Sciences (India)

    Mehran Shahmansouri


    Arbitrary amplitude dust-acoustic (DA) solitary waves in an unmagnetized and collisionless quantum dusty plasma comprising cold dust particles, kappa ()-distributed ions and degenerate electrons are investigated. The influence of suprathermality and quantum effects on the linear dispersion relation of DA waves is investigated. Then, the effect of -distributed ions and degenerate electrons on the existence domain of solitons is discussed in the space of (, ). The comparison of the existence domain for higher and lower values of shows that suprathermality results in propagation of solitons with lower values of Mach number, and the quantum effects, lead to a higher values of Mach number. The existence domain of solitons for nondegenerate -distributed electrons is considered for comparison with effect of degenerate electrons. Also, we found that the Sagdeev potential well becomes deeper and wider as $_{F-i}$ decreases, as for lower values, the influence of quantum effects on the Sagdeev pseudopotential profile is smaller.

  9. Development of immunoglobulin lambda-chain-positive B cells, but not editing of immunoglobulin kappa-chain, depends on NF-kappaB signals. (United States)

    Derudder, Emmanuel; Cadera, Emily J; Vahl, J Christoph; Wang, Jing; Fox, Casey J; Zha, Shan; van Loo, Geert; Pasparakis, Manolis; Schlissel, Mark S; Schmidt-Supprian, Marc; Rajewsky, Klaus


    By genetically ablating IkappaB kinase (IKK)-mediated activation of the transcription factor NF-kappaB in the B cell lineage and by analyzing a mouse mutant in which immunoglobulin lambda-chain-positive B cells are generated in the absence of rearrangements in the locus encoding immunoglobulin kappa-chain, we define here two distinct, consecutive phases of early B cell development that differ in their dependence on IKK-mediated NF-kappaB signaling. During the first phase, in which NF-kappaB signaling is dispensable, predominantly kappa-chain-positive B cells are generated, which undergo efficient receptor editing. In the second phase, predominantly lambda-chain-positive B cells are generated whose development is ontogenetically timed to occur after rearrangements of the locus encoding kappa-chain. This second phase of development is dependent on NF-kappaB signals, which can be substituted by transgenic expression of the prosurvival factor Bcl-2.

  10. Dissociation between skeletal muscle inhibitor-{kappa}B kinase/nuclear factor-{kappa}B pathway activity and insulin sensitivity in nondiabetic twins

    DEFF Research Database (Denmark)

    Friedrichsen, Martin; Ribel-Madsen, Rasmus; Wojtaszewski, Jørgen


    Context: Several studies suggest a link between increased activity of the inflammatory inhibitor-kappaB kinase/nuclear factor-kappaB (IKK/NF-kappaB) pathway in skeletal muscle and insulin resistance. Objective: We aimed to study the regulation of skeletal muscle IKK/NF-kappaB pathway activity...... as well as the association with glucose metabolism and skeletal muscle insulin signaling. Methods: The study population included a metabolically well-characterized cohort of young and elderly predominantly nondiabetic twins (n = 181). Inhibitor-kappaBbeta (IkappaBbeta) protein levels are negatively...... associated with IKK/NF-kappaB pathway activity and were used to evaluate pathway activity with p65 levels included as loading control. This indirect measure for IKK/NF-kappaB pathway activity was validated by a p65 binding assay. Results: Evaluating the effects of heritability, age, sex, obesity, aerobic...


    Directory of Open Access Journals (Sweden)

    Jacob BABAYEMI


    Full Text Available Supplementary values of unconventional browse Tephrosia bracteolata (TB and Tephrosia candida (TC and commonly utilized browse plants Gliricidia sepium (GS and Leucaena leucocephala (LL were studied in goats grazed on a rangeland in the dry season. Crude protein (g/Kg DM content of TC (19.25 compared favourably to those of GS (19.78 and that of LL (19.91 while that of TB was low (14.25. Total cell wall content, neutral detergent fi bre (NDF, g/Kg DM was lower in both TB (56.03 and TC (59.11 than in GS (61.20 and LL (37.50. Dry matter intake (g/d of TB (87.39 was signifi cantly higher than that of TC (76.49 while similar values were recorded in GS (63.81 and LL (63.31. Improved daily weight gain (g/d of 14.88, 17.86, 14.88 and 17.86 were obtained when goats were fed TB, TC, GS and LL browse supplements responsively compared to the daily gain of 11.90 from the unsuplemented goats. The digestibility of CP, NDF and ADF in both TB and TC compared favourably to those of GS and LL. The fi ndings from this study have shown that Tephrosia bracteolata and Tephrosia candida can be used as alternative browse supplement for goats grazing on natural grassland in the dry season to achieve improved weight gain. This will translate to a reduction in the pressure on the commonly use browse like Gliricidia sepium and Leucaena leucocephala.

  12. A tumor-associated antigen specific for human kappa myeloma cells



    A monoclonal antibody (K-1-21) raised against a kappa Bence Jones protein exhibits unique binding properties to malignant plasma cells. K- 1-21 is an IgG1 kappa antibody that reacts with human kappa light chains in free form, but shows no reactivity with heavy chain- associated kappa light chains. By immunofluorescence, K-1-21 binds to the surface of LICR LON/HMy2 (HMy2) kappa myeloma cells and to plasma cells from a majority (8/11) of patients with various types of kappa myeloma; it did not ...

  13. Inhibition of proteasome activity, nuclear factor-KappaB translocation and cell survival by the antialcoholism drug disulfiram. (United States)

    Lövborg, Henrik; Oberg, Fredrik; Rickardson, Linda; Gullbo, Joachim; Nygren, Peter; Larsson, Rolf


    The proteasome pathway is an important target for anticancer drug development. Here, we identify the antialcoholism drug disulfiram and its analogue pyrrolidine dithiocarbamate (PDTC) as inhibitors of the 26S proteasome activity in a cell-based screening assay. As expected for proteasome inhibitors, these compounds also inhibited TNF-alpha-induced nuclear factor-KappaB (NF-KappaB) translocation and were cytotoxic. Disulfiram was more cytotoxic against chronic lymphocytic leukemia cells compared to peripheral blood mononuclear cells (PBMC) at clinically achievable concentrations. Proteasome and NF-KappaB inhibition were achieved with a potency in the same range as that of the clinically used proteasome inhibitor bortezomib. Disulfiram was also able to induce accumulation of p27(Kip1) and to prolong the half-life of c-Myc, both targets for proteasome-dependent degradation. It is concluded that the previously observed antitumoral and NF-KappaB inhibiting activity of disulfiram and PDTC could be attributed to their inhibition of the 26S proteasome.

  14. On the mechanisms of kappa-opioid-induced diuresis. (United States)

    Blackburn, T. P.; Borkowski, K. R.; Friend, J.; Rance, M. J.


    In conscious saline loaded rats, the kappa-opioid agonists tifluadom, U50488, and ethylketocyclazocine, given subcutaneously, induced a characteristic diuresis which could be antagonized by naloxone. Bilateral adrenal demedullation significantly reduced adrenal gland catecholamine content and plasma adrenaline levels, but did not significantly affect plasma corticosterone levels, indicating that the adrenal cortex remained both intact and functional. Seven days following bilateral adrenal demedullation, the subcutaneous administration of the kappa-agonists no longer induced diuresis. However, demedullation did not affect the diuretic response to frusemide or clonidine, nor did it affect the antidiuretic response induced by the mu-opioid agonists morphine and buprenorphine. Adrenal catecholamines do not appear to be involved in kappa-opioid-induced diuresis, since pretreatment with propranolol, prazosin and idazoxan did not affect the diuretic response in intact animals. The results indicate a link between the adrenal medulla and kappa-opioid-induced diuresis and suggest that a peripheral mechanism may also be involved in mediating this effect. PMID:3542107

  15. Kappa opioid receptors stimulate phosphoinositide turnover in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Periyasamy, S.; Hoss, W. (Univ. of Toledo, OH (USA))


    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.

  16. Remarks on differential calculus over $\\kappa$-Minkowski space

    CERN Document Server

    Juric, Tajron; Strajn, Rina


    Unified graded differential algebra, generated by $\\kappa$-Minkowski noncommutative (NC) coordinates, Lorentz generators and anticommuting one-forms, is constructed. It is compatible with $\\kappa$-Poncar\\'e-Hopf algebra. For time- and space-like deformations, the super-Jacobi identities are not satisfied. By introducing additional generator, interpreted as exterior derivative, we find a unique algebra that satisfies all super-Jacobi identities. It is universal and valid for all type of deformations (time-, space-, and light-like). For time-like deformations this algebra coincides with the one in [hep-th/9409014]. Different realizations of our algebra in terms of super-Heisenberg algebra are presented. For light-like deformations we get 4D bicovariant calculus, with $\\kappa$-Poncar\\'e-Hopf algebra and present the corresponding twist, which is written in a covariant way, using Poncar\\'e generators only. In the time- and space-like case this twist leads to $\\kappa$-Snyder space. Our results might lead to applica...

  17. Kappa-distributions and coronal heating. (Slovak Title: Kappa-distribúcie a ohrev koróny) (United States)

    Dudík, J.; Dzifčáková, E.; Kulinová, A.; Karlický, M.


    Particle energy kappa-distributions (distributions with non-thermal tails) have been diagnosed in plasma of the transition region and also in solar flares. Theoretical models suggest a link between kappa-distributions and dynamic heating of the corona. Since the presence of non-thermal distributions leads to changes in intensities of emission lines, we have examined their effect on the total radiation losses of the corona as well as responses of the EUV and X-ray filters. Temperature responses of the filters are wider for kappa-distributions than in the case of the Maxwell distribution, and their respective maxima are shifted towards higher temperatures. On the other hand, the total radiation losses of the corona are lower compared to the Maxwell distribution except for the extreme non-thermal case. This means that lower heating energy is needed to reach the same corona temperature in case of kappa-distributions. In this work we discuss the effect of element abundances and specific ions on the total radiation losses of the corona.

  18. Nuclear factor-kappa B localization and function within intrauterine tissues from term and preterm labor and cultured fetal membranes

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    Kusanovic Juan P


    Full Text Available Abstract Background The objective of this study was to quantify the nuclear localization and DNA binding activity of p65, the major transactivating nuclear factor-kappa B (NF-kappaB subunit, in full-thickness fetal membranes (FM and myometrium in the absence or presence of term or preterm labor. Methods Paired full-thickness FM and myometrial samples were collected from women in the following cohorts: preterm no labor (PNL, N = 22, spontaneous preterm labor (PTL, N = 21, term no labor (TNL, N = 23, and spontaneous term labor (STL, N = 21. NF-kappaB p65 localization was assessed by immunohistochemistry, and DNA binding activity was evaluated using an enzyme-linked immunosorbent assay (ELISA-based method. Results Nuclear p65 labeling was rare in amnion and chorion, irrespective of clinical context. In decidua, nuclear p65 labeling was greater in the STL group relative to the TNL cohort, but there were no differences among the TNL, PTL, and PNL cohorts. In myometrium, diffuse p65 nuclear labeling was significantly associated with both term and preterm labor. There were no significant differences in ELISA-based p65 binding activity in amnion, choriodecidual, and myometrial specimens in the absence or presence of term labor. However, parallel experiments using cultured term fetal membranes demonstrated high levels of p65-like binding even the absence of cytokine stimulation, suggesting that this assay may be of limited value when applied to tissue specimens. Conclusions These results suggest that the decidua is an important site of NF-kappaB regulation in fetal membranes, and that mechanisms other than cytoplasmic sequestration may limit NF-kappaB activation prior to term.

  19. Schild (apparent pA2) analysis of a kappa-opioid antagonist in Planaria. (United States)

    Raffa, Robert B; Baron, David A; Tallarida, Ronald J


    Previous investigators have provided radioimmunological and immunocytochemical evidence for an enkephalinergic (opioid) system in Planaria and described naloxone-sensitive qualitative behavioral responses to kappa-opioid receptor agonists. We report the application of Schild-analysis to the antagonism of a selective kappa agonist (U-50,488H) by a selective kappa antagonist (nor-BNI) in a quantitative in vivo endpoint. The results provide further evidence of a kappa-opioid-like receptor in planarians.

  20. Heat Shock Factor-1 and Nuclear Factor-kappaB Are Systemically Activated in Human Acute Pancreatitis

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    Derek A O’Reilly


    Full Text Available Context :Nuclear factor-kappa B (NFkappaB is a transcription factor for a wide range of proinflammatory mediators while heat shock factor-1 (HSF-1 transcribes stress proteins that protect against cellular damage. Both are attractive therapeutic targets, undergoing investigation in other acute inflammatory conditions, such as sepsis. Objective :To evaluate the role of the transcription factors NF-kappaB and HSF-1 in human acute pancreatitis and their relationship to cytokine/chemokine production, disease severity and outcome. Patients :Twenty-four patients with acute pancreatitis and 12 healthy controls. Main outcome measures :Peripheral blood mononuclear cells were isolated. NF-kappaB and HSF-1 were measured by electrophoretic mobility shift assay. Soluble tumor necrosis factor (TNF receptor II and interleukin-8 were measured by ELISA. Acute physiology scores (APS, APACHE II scores and final Atlanta designations of severity were also determined. Results: Systemic NF-kappaB activation occurs in acute pancreatitis compared to healthy controls (P=0.004. However, there was no significant difference between those with mild and severe disease (P=0.685. Systemic activation of HSF-1 was observed in acute pancreatitis compared to healthy controls although this did not reach statistical significance (P=0.053. Activation, however, was greatest in those who had a final Atlanta designation of mild pancreatitis compared to those who had a severe attack of acute pancreatitis (P=0.036. Furthermore, HSF-1 was inversely correlated with acute physiology score (APS; r=-0.49, P=0.019 and APACHE II score (r=-0.47, P=0.026. Conclusions: Both NF-kappaB and HSF-1 are systemically activated in human acute pancreatitis. HSF-1 activation may protect against severity of pancreatitis

  1. Commensal-induced regulatory T cells mediate protection against pathogen-stimulated NF-kappaB activation.

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    Caitlin O'Mahony

    Full Text Available Host defence against infection requires a range of innate and adaptive immune responses that may lead to tissue damage. Such immune-mediated pathologies can be controlled with appropriate T regulatory (Treg activity. The aim of the present study was to determine the influence of gut microbiota composition on Treg cellular activity and NF-kappaB activation associated with infection. Mice consumed the commensal microbe Bifidobacterium infantis 35624 followed by infection with Salmonella typhimurium or injection with LPS. In vivo NF-kappaB activation was quantified using biophotonic imaging. CD4+CD25+Foxp3+ T cell phenotypes and cytokine levels were assessed using flow cytometry while CD4+ T cells were isolated using magnetic beads for adoptive transfer to naïve animals. In vivo imaging revealed profound inhibition of infection and LPS induced NF-kappaB activity that preceded a reduction in S. typhimurium numbers and murine sickness behaviour scores in B. infantis-fed mice. In addition, pro-inflammatory cytokine secretion, T cell proliferation, and dendritic cell co-stimulatory molecule expression were significantly reduced. In contrast, CD4+CD25+Foxp3+ T cell numbers were significantly increased in the mucosa and spleen of mice fed B. infantis. Adoptive transfer of CD4+CD25+ T cells transferred the NF-kappaB inhibitory activity. Consumption of a single commensal micro-organism drives the generation and function of Treg cells which control excessive NF-kappaB activation in vivo. These cellular interactions provide the basis for a more complete understanding of the commensal-host-pathogen trilogue that contribute to host homeostatic mechanisms underpinning protection against aberrant activation of the innate immune system in response to a translocating pathogen or systemic LPS.

  2. Study Of Calcium And Potassium Different Nature Strength Gel Kappa-Carrageenan

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    Петро Васильович Гурський


    Full Text Available The influence of certain organic and mineral salts of potassium and calcium for strength gel kappa-carrageenan. The influence of the mass concentration of individual calcium for strength gels with different content kappa-carrageenan. Grounded mass concentration of some calcium salts for use in the composition of the jelly for sweet and savory dishes based on kappa-carrageenan

  3. Value-Range Analysis of C Programs (United States)

    Simon, Axel

    In 1988, Robert T. Morris exploited a so-called buffer-overflow bug in finger (a dæmon whose job it is to return information on local users) to mount a denial-of-service attack on hundreds of VAX and Sun-3 computers [159]. He created what is nowadays called a worm; that is, a crafted stream of bytes that, when sent to a computer over the network, utilises a buffer-overflow bug in the software of that computer to execute code encoded in the byte stream. In the case of a worm, this code will send the very same byte stream to other computers on the network, thereby creating an avalanche of network traffic that ultimately renders the network and all computers involved in replicating the worm inaccessible. Besides duplicating themselves, worms can alter data on the host that they are running on. The most famous example in recent years was the MSBlaster32 worm, which altered the configuration database on many Microsoft Windows machines, thereby forcing the computers to reboot incessantly. Although this worm was rather benign, it caused huge damage to businesses who were unable to use their IT infrastructure for hours or even days after the appearance of the worm. A more malicious worm is certainly conceivable [187] due to the fact that worms are executed as part of a dæmon (also known as "service" on Windows machines) and thereby run at a privileged level, allowing access to any data stored on the remote computer. While the deletion of data presents a looming threat to valuable information, even more serious uses are espionage and theft, in particular because worms do not have to affect the running system and hence may be impossible to detect.

  4. Sigma, Kappa, fo(980) and a0(980)

    CERN Document Server

    Bugg, D V


    Both sigma and kappa are well established from E791 data on D->3pi and Ds->Kpipi and BES II data on J/Psi -> omega pi pi and KKpipi. These fits are accurately consistent with pipi and Kpi elastic scattering when one allows for the Adler zero which arises from Chiral Symmetry Breaking. The phase variation with mass is consistent between elastic scattering and production data. Possible interpretations of sigma, kappa, fo(980) and ao(980) are explored. The experimental ratio g^2(fo(980)->KK)/g^2(ao(980)->KK) = 2.7+-0.5 suggests strongly that fo(980) has a large KK component in its wave function. This is a natural consequence of its pole lying very close to the KK threshold.

  5. NIRS Characterization of Paper Pulps to Predict Kappa Number

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    Ana Moral


    Full Text Available Rice is one of the most abundant food crops in the world and its straw stands as an important source of fibres both from an economic and an environmental point of view. Pulp characterization is of special relevance in works involving alternative raw materials, since pulp properties are closely linked to the quality of the final product. One of the analytical techniques that can be used in pulp characterization is near-infrared spectroscopy (NIRS. The use of NIRS has economic and technical advantages over conventional techniques. This paper aims to discuss the convenience of using NIRS to predict Kappa number in rice straw pulps produced under different conditions. We found that the resulting Kappa number can be acceptably estimated by NIRS, as the errors obtained with that method are similar to those found for other techniques.

  6. Radio Emissions from Plasma with Electron Kappa-Distributions (United States)

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


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

  7. Inhibition of the nuclear factor kappa B (NF-kappa B) pathway by tetracyclic kaurene diterpenes in macrophages. Specific effects on NF-kappa B-inducing kinase activity and on the coordinate activation of ERK and p38 MAPK. (United States)

    Castrillo, A; de Las Heras, B; Hortelano, S; Rodriguez, B; Villar, A; Bosca, L


    The anti-inflammatory action of most terpenes has been explained in terms of the inhibition of nuclear factor kappaB (NF-kappaB) activity. Ent-kaurene diterpenes are intermediates of the synthesis of gibberellins and inhibit the expression of NO synthase-2 and the release of tumor necrosis factor-alpha in J774 macrophages challenged with lipopolysaccharide. These diterpenes inhibit NF-kappaB and IkappaB kinase (IKK) activation in vivo but failed to affect in vitro the function of NF-kappaB, the phosphorylation and targeting of IkappaBalpha, and the activity of IKK-2. Transient expression of NF-kappaB-inducing kinase (NIK) activated the IKK complex and NF-kappaB, a process that was inhibited by kaurenes, indicating that the inhibition of NIK was one of the targets of these diterpenes. These results show that kaurenes impair the inflammatory signaling by inhibiting NIK, a member of the MAPK kinase superfamily that interacts with tumor necrosis factor receptor-associated factors, and mediate the activation of NF-kappaB by these receptors. Moreover, kaurenes delayed the phosphorylation of p38, ERK1, and ERK2 MAPKs, but not that of JNK, in response to lipopolysaccharide treatment of J774 cells. The absence of a coordinate activation of MAPK and IKK might contribute to a deficient activation of NF-kappaB that is involved in the anti-inflammatory activity of these molecules.

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

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    Jomary, C.; Beaudet, A. (McGill Univ., Montreal, Quebec (Canada)); Gairin, J.E. (Centre National de la Recherche Scientifique, Toulouse (France))


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

  9. Persistent activation of nuclear factor-kappa B and expression of pro-inflammatory cytokines in bone marrow cells after exposure of mice to protons (United States)

    Rithidech, Kanokporn; Reungpatthanaphong, Paiboon; Honikel, Louise; Whorton, Elbert

    Protons are the most abundant component of solar particle events (SPEs) in space. Information is limited on early-and late-occurring in vivo biological effects of exposure to protons at doses and dose rates that are similar to what astronauts encounter in space. We conducted a study series to fill this knowledge gap. We focused on the biological effects of 100 MeV/n protons, which are one of the most abundant types of protons induced during SPEs. We gave BALB/cJ mice a whole-body exposure to 0.5 or 1.0 Gy of 100 MeV/n protons, delivered at 0.5 or 1.0 cGy/min. These doses and dose rates of protons were selected because they are comparable to those of SPEs taking place in space. For each dose and dose rate of 100 MeV/n protons, mice exposed to 0 Gy of protons served as sham controls. Mice included in this study were also part of a study series conducted to examine the extent and the mechanisms involved in in vivo induction of genomic instability (expressed as late-occurring chromosome instability) by 100 MeV/n protons. Bone marrow (BM) cells were collected from groups of mice for analyses at different times post-exposure, i.e. early time-points (1.5, 3, and 24 hr) and late time-points (1 and 6 months). At each harvest time, there were five mice per treatment group. Several endpoints were used to investigate the biological effects of 100 MeV/n protons in BM cells from irradiated and sham control mice. The scope of this study was to determine the dose-rate effects of 0.5 Gy of 100 MeV/n protons in BM cells on the kinetics of nuclear factor-kappa B (NF-kappa B) activation and the expression of selected NF-kappa B target proteins known to be involved in inflammatory response, i.e. pro-inflammatory cytokines (TNF-alpha, IL-1 beta, and IL-6). Significantly high levels (p values ranging from p¡0.01 and p¡0.05) of activated NF-kappa B were observed in BM cells collected from irradiated mice, relative to those obtained from the corresponding sham controls, at all time

  10. Ion-acoustic double layers in a five component cometary plasma with kappa described electrons and ions (United States)

    Michael, Manesh; Venugopal, C.; Sreekala, G.; Willington, Neethu Theresa; Sebastian, Sijo


    We investigate the propagation characteristics of Ion-acoustic solitons and double layers in a five component cometary plasma consisting of positively and negatively charged oxygen ions, kappa described hydrogen ions, hot solar electrons, and slightly colder cometary electrons. The KdV and modified KdV equations are derived for the system and its solution is plotted for different kappa values and negatively charged oxygen ion densities. It is found that the strength of double layer increases with increasing spectral indices. It, however, decreases with increasing negatively charged oxygen ion densities. The parameter for the transition from compressive to rarefactive soliton is also specified. The presence of negatively charged oxygen ions can significantly affect the nonlinearity coefficients (both quadratic and cubic) of a double layer.

  11. Pro-apoptotic role of NF-kappaB: implications for cancer therapy. (United States)

    Radhakrishnan, Senthil K; Kamalakaran, Sitharthan


    Nuclear factor-kappaB (NF-kappaB) is generally viewed as anti-apoptotic and oncogenic, leading to a quest for its inhibitors. However, recent evidence suggests that in some situations NF-kappaB may promote apoptosis. Depending on the specific cell type and the stimulus involved, NF-kappaB activation may lead to either anti- or pro-apoptotic response. Both these effects can be mediated by NF-kappaB in a context-dependent manner by selectively regulating its target genes. In this review, we discuss the evidence for NF-kappaB's pro-apoptotic role and explore the possible mechanisms behind it. We emphasize that rather than trying to inhibit NF-kappaB in cancer therapy, agents should be developed to unleash its pro-apoptotic ability.

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

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    Hwang, Insun; Ha, Danbee [College of Veterinary Medicine and Applied Radiological Science Institute, Jeju National University, Jeju 690-756 (Korea, Republic of); Ahn, Ginnae [Department of Marine Life Science, Jeju National University, Jeju 690-756 (Korea, Republic of); Park, Eunjin; Joo, Haejin [College of Veterinary Medicine and Applied Radiological Science Institute, Jeju National University, Jeju 690-756 (Korea, Republic of); Jee, Youngheun, E-mail: [College of Veterinary Medicine and Applied Radiological Science Institute, Jeju National University, Jeju 690-756 (Korea, Republic of)


    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.

  13. Introducing spatial information into predictive NF-kappaB modelling--an agent-based approach.

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    Mark Pogson

    Full Text Available Nature is governed by local interactions among lower-level sub-units, whether at the cell, organ, organism, or colony level. Adaptive system behaviour emerges via these interactions, which integrate the activity of the sub-units. To understand the system level it is necessary to understand the underlying local interactions. Successful models of local interactions at different levels of biological organisation, including epithelial tissue and ant colonies, have demonstrated the benefits of such 'agent-based' modelling. Here we present an agent-based approach to modelling a crucial biological system--the intracellular NF-kappaB signalling pathway. The pathway is vital to immune response regulation, and is fundamental to basic survival in a range of species. Alterations in pathway regulation underlie a variety of diseases, including atherosclerosis and arthritis. Our modelling of individual molecules, receptors and genes provides a more comprehensive outline of regulatory network mechanisms than previously possible with equation-based approaches. The method also permits consideration of structural parameters in pathway regulation; here we predict that inhibition of NF-kappaB is directly affected by actin filaments of the cytoskeleton sequestering excess inhibitors, therefore regulating steady-state and feedback behaviour.

  14. Systemic blood loss affects NF-kappa B regulatory mechanisms in the lungs. (United States)

    Moine, P; Shenkar, R; Kaneko, D; Le Tulzo, Y; Abraham, E


    The nuclear regulatory factor (NF)-kappa B is activated in the lungs of patients with acute respiratory distress syndrome (ARDS). In experimental models of acute lung injury, activation of NF-kappa B contributes to the increased expression of immunoregulatory cytokines and other proinflammatory mediators in the lungs. Because of the important role that NF-kappa B activation appears to play in the development of acute lung injury, we examined cytoplasmic and nuclear NF-kappa B counterregulatory mechanisms in lung mononuclear cells, using a murine model in which inflammatory lung injury develops after blood loss. Sustained activation of NF-kappa B was present in lung mononuclear cells over the 4-h period after blood loss. The activation of NF-kappa B after hemorrhage was accompanied by alterations in levels of the NF-kappa B regulatory proteins I kappa B alpha and Bcl-3. Cytoplasmic and nuclear I kappa B alpha were increased and nuclear Bcl-3 was decreased during the first hour after blood loss, but, by 4 h posthemorrhage, cytoplasmic and nuclear I kappa B alpha levels were decreased and nuclear levels of Bcl-3 were increased. Inhibition of xanthine oxidase activity in otherwise unmanipulated unhemorrhaged mice resulted in increased levels of I kappa B alpha and decreased amounts of Bcl-3 in nuclear extracts from lung mononuclear cells. No changes in the levels of nuclear I kappa B alpha or Bcl-3 occurred after hemorrhage when xanthine oxidase activity was inhibited. These results demonstrate that blood loss, at least partly through xanthine oxidase-dependent mechanisms, produces alterations in the levels of both I kappa B alpha and Bcl-3 in lung mononuclear cell populations. The effects of hemorrhage on proteins that regulate activation of NF-kappa B may contribute to the frequent development of inflammatory lung injury in this setting.

  15. Treatment of kappa in Recent Western US Seismic Nuclear Plant Probabilistic Seismic Hazard Studies (United States)

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


    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.

  16. Neuroadaptations in human chronic alcoholics: dysregulation of the NF-kappaB system.

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    Anna Okvist

    Full Text Available BACKGROUND: Alcohol dependence and associated cognitive impairments apparently result from neuroadaptations to chronic alcohol consumption involving changes in expression of multiple genes. Here we investigated whether transcription factors of Nuclear Factor-kappaB (NF-kappaB family, controlling neuronal plasticity and neurodegeneration, are involved in these adaptations in human chronic alcoholics. METHODS AND FINDINGS: Analysis of DNA-binding of NF-kappaB (p65/p50 heterodimer and the p50 homodimer as well as NF-kappaB proteins and mRNAs was performed in postmortem human brain samples from 15 chronic alcoholics and 15 control subjects. The prefrontal cortex involved in alcohol dependence and cognition was analyzed and the motor cortex was studied for comparison. The p50 homodimer was identified as dominant kappaB binding factor in analyzed tissues. NF-kappaB and p50 homodimer DNA-binding was downregulated, levels of p65 (RELA mRNA were attenuated, and the stoichiometry of p65/p50 proteins and respective mRNAs was altered in the prefrontal cortex of alcoholics. Comparison of a number of p50 homodimer/NF-kappaB target DNA sites, kappaB elements in 479 genes, down- or upregulated in alcoholics demonstrated that genes with kappaB elements were generally upregulated in alcoholics. No significant differences between alcoholics and controls were observed in the motor cortex. CONCLUSIONS: We suggest that cycles of alcohol intoxication/withdrawal, which may initially activate NF-kappaB, when repeated over years downregulate RELA expression and NF-kappaB and p50 homodimer DNA-binding. Downregulation of the dominant p50 homodimer, a potent inhibitor of gene transcription apparently resulted in derepression of kappaB regulated genes. Alterations in expression of p50 homodimer/NF-kappaB regulated genes may contribute to neuroplastic adaptation underlying alcoholism.

  17. The coupling between enhancer activity and hypomethylation of kappa immunoglobulin genes is developmentally regulated

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    Kelley, D.E.; Pollok, B.A.; Atchison, M.L.; Perry, R.P.


    Previous studies have indicated that immunoglobulin enhancers are essential for establishing transcriptional competence but not for maintaining the activity of constitutively transcribed genes. To understand the basis for this developmental shift away from dependence on enhancer function, the authors investigated the relationship between transcriptional activity and methylation status of the immunoglobulin kappa-light-chain genes (kappa genes) in mouse cell lines representing different stages of B-cell maturation. Using pre-B-cell lines in which the level of a critical kappa enhancer-binding factor, NF-kappaB, was controlled by the administration of withdrawal of lipopolysaccharide and plasmacytoma lines that either contain or lack this factor, they studied the properties of endogenous kappa genes and of transfected kappa genes which were stably integrated into the genomes of these cells. In the pre-B cells, the exogenous (originally unmethylated) kappa genes, as well as the endogenous kappa genes, were fully methylated and persistently dependent on enhancer function, even after more than 30 generations in a transcriptionally active state. In plasmacytoma cells, the endogenous kappa genes were invariably hypomethylated, whereas exogenous kappa genes were hypomethylated only in cells that contain NF-kappaB and are thus permissive for kappa enhancer function. These results indicate that the linkage of hypomethylation to enhancer-dependent activation of kappa transcription occurs after the pre-B-cell stage of development. The change in methylation status, together with associated changes in chromatin structure, may suffice to eliminate or lessen the importance of the enhancer for the maintenance of the transcriptionally active state.

  18. Cardiorenal Effects of Kappa Opioid Peptides During Ontogeny

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    Wei Qi


    Full Text Available This review focuses on the physiological roles for kappa opioid receptors (KORs in adult animals and humans, as well as in the developing newborn animal. Our recent findings have provided new information that under physiological conditions in conscious newborn animals, activation of KORs with the selective agonist, U-50488H, results in an aquaresis, as previously observed in adult animals and humans. In addition, we have shown in conscious lambs that KORs modulate systemic and renal haemodynamics as well as the arterial baroreflex control of heart rate, providing a previously unidentified role for KORs.

  19. Behavioral meaningful opioidergic stimulation activates kappa receptor gene expression

    Directory of Open Access Journals (Sweden)

    E. Teodorov


    Full Text Available 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 kappa 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Arshad, Kashif [National Center for Physics (NCP), Quaid-i-Azam University Campus, Shahdra Valley Road, Islamabad 44000 (Pakistan); Pakistan Institute of Engineering and Applied Sciences, P.O. Nilore, Islamabad and University of Wah, Wah Cantt 47040 (Pakistan); Ehsan, Zahida, E-mail: [National Center for Physics (NCP), Quaid-i-Azam University Campus, Shahdra Valley Road, Islamabad 44000 (Pakistan); Universita degli Studi del Molise, 86090 Pesche - IS (Italy); INFN Sezione di Napoli, 80126 Napoli (Italy); Department of Physics, COMSATS Institute of Information Technology (CIIT), Defence Road, Off Raiwind Road, Lahore 86090 (Pakistan); Khan, S. A. [National Center for Physics (NCP), Quaid-i-Azam University Campus, Shahdra Valley Road, Islamabad 44000 (Pakistan); Mahmood, S. [Theoretical Plasma Physics Division, PINSTEC, PO Box Nilore, Islamabad 44000 (Pakistan)


    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.

  1. Assessing agreement on classification tasks the kappa statistic

    CERN Document Server

    Carletta, J


    Currently, computational linguists and cognitive scientists working in the area of discourse and dialogue argue that their subjective judgments are reliable using several different statistics, none of which are easily interpretable or comparable to each other. Meanwhile, researchers in content analysis have already experienced the same difficulties and come up with a solution in the kappa statistic. We discuss what is wrong with reliability measures as they are currently used for discourse and dialogue work in computational linguistics and cognitive science, and argue that we would be better off as a field adopting techniques from content analysis.

  2. Kappa distributions: theory and applications in space plasmas

    CERN Document Server

    Pierrard, V


    Particle velocity distribution functions (VDF) in space plasmas often show non Maxwellian suprathermal tails decreasing as a power law of the velocity. Such distributions are well fitted by the so-called Kappa distribution. The presence of such distributions in different space plasmas suggests a universal mechanism for the creation of such suprathermal tails. Different theories have been proposed and are recalled in this review paper. The suprathermal particles have important consequences concerning the acceleration and the temperature that are well evidenced by the kinetic approach where no closure requires the distributions to be nearly Maxwellians. Moreover, the presence of the suprathermal particles take an important role in the wave-particle interactions.

  3. Electron acoustic waves in a magnetized plasma with kappa distributed ions

    Energy Technology Data Exchange (ETDEWEB)

    Devanandhan, S.; Lakhina, G. S. [Indian Institute of Geomagnetism, Navi Mumbai (India); Singh, S. V. [Indian Institute of Geomagnetism, Navi Mumbai (India); School of Physics, University of Kwazulu-Natal, Durban (South Africa); Bharuthram, R. [University of the Western Cape, Bellville (South Africa)


    Electron acoustic solitary waves in a two component magnetized plasma consisting of fluid cold electrons and hot superthermal ions are considered. The linear dispersion relation for electron acoustic waves is derived. In the nonlinear regime, the energy integral is obtained by a Sagdeev pseudopotential analysis, which predicts negative solitary potential structures. The effects of superthermality, obliquity, temperature, and Mach number on solitary structures are studied in detail. The results show that the superthermal index {kappa} and electron to ion temperature ratio {sigma} alters the regime where solitary waves can exist. It is found that an increase in magnetic field value results in an enhancement of soliton electric field amplitude and a reduction in soliton width and pulse duration.

  4. NF-kappaB inhibitors for the treatment of inflammatory diseases and cancer. (United States)

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


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

  5. Realizations of $\\kappa$-Minkowski space, Drinfeld twists and related symmetry algebras

    CERN Document Server

    Juric, Tajron; Pikutic, Danijel


    Realizations of $\\kappa$-Minkowski space linear in momenta are studied for time-, space- and light-like deformations. We construct and classify all such linear realizations and express them in terms of $\\mathfrak{gl}(n)$ generators. There are three one-parameter families of linear realizations for time-like and space-like deformations, while for light-like deformations, there are only four linear realizations. The relation between deformed Heisenberg algebra, star product, coproduct of momenta and twist operator is presented. It is proved that for each linear realization there exists Drinfeld twist satisfying normalization and cocycle conditions. $\\kappa$-deformed $\\mathfrak{igl}(n)$-Hopf algebras are presented for all cases. The $\\kappa$-Poincar\\'e-Weyl and $\\kappa$-Poincar\\'e-Hopf algebras are discussed. Left-right dual $\\kappa$-Minkowski algebra is constructed from the transposed twists. The corresponding realizations are nonlinear. All known Drinfeld twists related to $\\kappa$-Minkowski space are obtained...

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

    Energy Technology Data Exchange (ETDEWEB)

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


    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).

  7. Rate constants of reactions of {kappa}-carrageenan with hydrated electron and hydroxyl radical

    Energy Technology Data Exchange (ETDEWEB)

    Abad, L.V. [Nuclear Professional School, School of Engineering Laboratory, University of Tokyo, 2-22 Shirakata-Shirane, Tokai, Naka, Ibaraki 319-1188 (Japan); Philippine Nuclear Research Institute, Commonwealth Avenue, Diliman, Quezon City (Philippines)], E-mail:; Saiki, S.; Kudo, H.; Muroya, Y.; Katsumura, Y. [Nuclear Professional School, School of Engineering Laboratory, University of Tokyo, 2-22 Shirakata-Shirane, Tokai, Naka, Ibaraki 319-1188 (Japan); Rosa, A.M. de la [Philippine Nuclear Research Institute, Commonwealth Avenue, Diliman, Quezon City (Philippines)


    The rate constants for the reactions of {kappa}-carrageenan with hydrated electron and hydroxyl radical was investigated by pulse radiolysis and laser photolysis. The kinetics of the reaction of hydrated electron indicates no seeming reaction with {kappa}-carrageenan. On the other hand, hydroxyl radical reacts very rapidly with {kappa}-carrageenan at a rate constant of approximately 1.2 x 10{sup 9} M{sup -1} s{sup -1}. This rate constant varies with pH.

  8. Inhibition of the canonical IKK/NF kappa B pathway sensitizes human cancer cells to doxorubicin. (United States)

    Tapia, Maria A; González-Navarrete, Irene; Dalmases, Alba; Bosch, Marta; Rodriguez-Fanjul, Vanesa; Rolfe, Mark; Ross, Jeffrey S; Mezquita, Jovita; Mezquita, Cristobal; Bachs, Oriol; Gascón, Pere; Rojo, Federico; Perona, Rosario; Rovira, Ana; Albanell, Joan


    The NF kappa B family is composed by five subunits (p65/RelA, c-Rel, RelB, p105-p50/NF kappa B(1), p100-p52/NF kappa B(2)) and controls the expression of many genes that participate in cell cycle, apoptosis, and other key cellular processes. In a canonical pathway, NF kappa B activation depends on the IKK complex activity, which is formed by three subunits (IKKalpha and IKKbeta and IKKgamma/NEMO). There is an alternative NF kappa B activation pathway that does not require IKKbeta or IKKgamma/NEMO, in which RelB is a major player. We report in a panel of human breast cancer cells that the IKK/NF kappa B system is generally overexpressed in breast cancer cells and there is heterogeneity in expression levels of individual members between different cell lines. Doxorubicin, an anticancer agent used in patients with breast cancer, activated NF kappa B and appeared to be less effective in cells expressing predominantly members of the canonical IKK/NF kappa B. Two NF kappa B inhibitors, bortezomib and NEMO-Binding Domain Inhibitory Peptide, prevented doxorubicin-induced NF kappa B activation and increased doxorubicin antitumor effects in BT-474 cells. Transient down-regulation of members of the canonical pathway (p65, p52, c-Rel and IKKgamma/NEMO) by siRNA in HeLa cells increased doxorubicin cytotoxicity. In contrast, silencing of RelB, a key subunit of the alternative pathway, had no evident effects on doxorubicin cytotoxicity. To conclude, NF kappa B inhibition sensitized cells to doxorubicin, implying directly p65, p52, c-Rel and IKKgamma/NEMO subunits in chemoresistance, but not RelB. These findings suggest that selective inhibition of the canonical NF kappa B pathway is sufficient to improve doxorubicin antitumor effects.

  9. Physiologic and serum biochemistry values in free-ranging Hoffmann's two-toed (Choloepus hoffmanni) and brown-throated three-toed (Bradypus variegatus) sloths immobilized using dexmedetomidine and ketamine. (United States)

    Kinney, Matthew E; Cole, Gretchen A; Vaughan, Christopher; Sladky, Kurt K


    Dexmedetomidine, a highly selective alpha-2 adrenergic agonist and dextrorotary enantiomer of medetomidine, was combined with ketamine and used to immobilize 14 free-ranging Choloepus hoffmanni (Hoffmann's two-toed sloths) and 11 Bradypus variegatus (brown-throated three-toed sloths) in Upala, Costa Rica. Following intramuscular injection of ketamine (2.1 mg/kg) and dexmedetomidine (11 microg/kg), heart rate, respiratory rate, and indirect systolic blood pressure were measured every 5 min for a total of 25 min. An iStat (CG8+) was used to evaluate serum biochemical and hematologic values during anesthesia. After 30 min of anesthesia, atipamezole (0.13 mg/kg) was administered intramuscularly, which resulted in rapid and smooth recoveries. Mean heart rate and respiratory rate remained unchanged in both C. hoffmanni and B. variegatus over time. Progressive decreases in mean indirect systolic blood pressure were documented in both species. Results of this study suggest a combination of dexmedetomidne and ketamine is a safe and effective anesthetic protocol for use in free-ranging C. hoffmanni and B. variegatus. Similar to other alpha-2 adrenergic agonist-based immobilization protocols, close monitoring of cardiovascular and respiratory parameters are recommended. This study also provides serum biochemical and hematologic data in free-ranging C. hoffmanni and B. variegatus.

  10. The (\\lambda, \\kappa)-Freese-Nation property for boolean algebras and compacta

    CERN Document Server

    Milovich, David


    We study a two-parameter generalization of the Freese-Nation Property of boolean algebras and its order-theoretic and topological consequences. For every regular infinite \\kappa, the (\\kappa,\\kappa)-FN, the (\\kappa^+,\\kappa)-FN, and the \\kappa-FN are known to be equivalent; we show that the family of properties (\\lambda,\\mu)-FN for \\lambda>\\mu form a true two-dimensional hierarchy that is robust with respect to coproducts, retracts, and the exponential operation. The (\\kappa,\\aleph_0)-FN in particular has strong consequences for base properties of compacta (stronger still for homogeneous compacta), and these consequences have natural duals in terms of special subsets of boolean algebras. We show that the (\\kappa,\\aleph_0)-FN also leads to a generalization of the equality of weight and \\pi-character in dyadic compacta. Elementary subalgebras and their duals, elementary quotient spaces, were originally used to define the (\\lambda, \\kappa)-FN and its topological dual, which naturally generalized from Stone space...

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

    Energy Technology Data Exchange (ETDEWEB)

    Raveh-Amit, Hadas; Hai, Naama; Rotem-Dai, Noa; Shahaf, Galit [The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences, The Cancer Research Center, Ben-Gurion University of the Negev (Israel); Gopas, Jacob [The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences, The Cancer Research Center, Ben-Gurion University of the Negev (Israel); The Department of Oncology, Soroka University Medical Center, Beer-Sheva 84105 (Israel); Livneh, Etta, E-mail: [The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences, The Cancer Research Center, Ben-Gurion University of the Negev (Israel)


    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.

  12. False vacuum energy dominated inflation with large $r$ and the importance of $\\kappa_s$

    CERN Document Server

    Antusch, Stefan; Nolde, David; Orani, Stefano


    We investigate to which extent and under which circumstances false vacuum energy ($V_0$) dominated slow-roll inflation is compatible with a large tensor-to-scalar ratio $r = O(0.1)$, as indicated by the recent BICEP2 measurement. With $V_0$ we refer to a constant contribution to the inflaton potential, present before a phase transition takes place and absent in the true vacuum of the theory, like e.g. in hybrid inflation. Based on model-independent considerations, we derive an upper bound on the possible amount of $V_0$ domination and highlight the importance of higher-order runnings of the scalar spectral index (beyond $\\alpha_s$) in order to realise scenarios of $V_0$ dominated inflation. We study the conditions for $V_0$ domination explicitly with an inflaton potential reconstruction around the inflaton field value 50 e-folds before the end of inflation, taking into account the present observational data. To this end, we provide the up-to-date parameter constraints within $\\Lambda$CDM + $r$ + $\\alpha_s$ + ...

  13. Behavioral meaningful opioidergic stimulation activates kappa receptor gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Teodorov, E. [Centro de Matemática, Computação e Cognição, Universidade Federal do ABC, São Paulo, SP (Brazil); Ferrari, M.F.R. [Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP (Brazil); Fior-Chadi, D.R. [Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP (Brazil); Camarini, R. [Departamento de Farmacologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP (Brazil); Felício, L.F. [Departamento de Patologia, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, São Paulo, SP (Brazil)


    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

  14. Measurement of Shoulder Range of Motion in Patients with Adhesive Capsulitis Using a Kinect. (United States)

    Lee, Seung Hak; Yoon, Chiyul; Chung, Sun Gun; Kim, Hee Chan; Kwak, Youngbin; Park, Hee-Won; Kim, Keewon


    Range of motion (ROM) measurements are essential for the evaluation for and diagnosis of adhesive capsulitis of the shoulder (AC). However, taking these measurements using a goniometer is inconvenient and sometimes unreliable. The Kinect (Microsoft, Seattle, WA, USA) is gaining attention as a new motion detecting device that is nonintrusive and easy to implement. This study aimed to apply Kinect to measure shoulder ROM in AC; we evaluated its validity by calculating the agreement of the measurements obtained using Kinect with those obtained using goniometer and assessed its utility for the diagnosis of AC. Both shoulders of 15 healthy volunteers and affected shoulders of 12 patients with AC were included in the study. The passive and active ROM of each were measured with a goniometer for flexion, abduction, and external rotation. Their active shoulder motions for each direction were again captured using Kinect and the ROM values were calculated. The agreement between the two measurements was tested with the intraclass correlation coefficient (ICC). Diagnostic performance using the Kinect ROM was evaluated with Cohen's kappa value. The cutoff values of the limited ROM were determined in the following ways: the same as passive ROM values, reflecting the mean difference, and based on receiver operating characteristic curves. The ICC for flexion/abduction/external rotation between goniometric passive ROM and the Kinect ROM were 0.906/0.942/0.911, while those between active ROMs and the Kinect ROMs were 0.864/0.932/0.925. Cohen's kappa values were 0.88, 0.88, and 1.0 with the cutoff values in the order above. Measurements of the shoulder ROM using Kinect show excellent agreement with those taken using a goniometer. These results indicate that the Kinect can be used to measure shoulder ROM and to diagnose AC as an alternative to goniometer.

  15. NF-kappaB regulatory mechanisms in alveolar macrophages from patients with acute respiratory distress syndrome. (United States)

    Moine, P; McIntyre, R; Schwartz, M D; Kaneko, D; Shenkar, R; Le Tulzo, Y; Moore, E E; Abraham, E


    Activation of the nuclear regulatory factor NF-kappaB occurs in the lungs of patients with the acute respiratory distress syndrome (ARDS) and may contribute to the increased expression of immunoregulatory cytokines and other proinflammatory mediators in this setting. Because of the important role that NF-kappaB activation appears to play in the development of acute lung injury, we examined cytoplasmic and nuclear NF-kapppaB counterregulatory mechanisms, involving IkappaB proteins, in alveolar macrophages obtained from 7 control patients without lung injury and 11 patients with established ARDS. Cytoplasmic levels of the NF-kappaB subunits p50, p65, and c-Rel were significantly decreased in alveolar macrophages from patients with ARDS, consistent with enhanced migration of liberated NF-kappaB dimers from the cytoplasm to the nucleus. Cytoplasmic and nuclear levels of IkappaBalpha were not significantly altered in alveolar macrophages from patients with established ARDS, compared with controls. In contrast, nuclear levels of Bcl-3 were significantly decreased in patients with ARDS compared with controls (P = 0.02). No IkappaBgamma, IkappaBbeta, or p105 proteins were detected in the cytoplasm of alveolar macrophages from control patients or patients with ARDS. The presence of activated NF-kappaB in alveolar macrophages from patients with established ARDS implies the presence of an ongoing stimulus for NF-kappaB activation. In this setting, appropriate counterregulatory mechanisms to normalize nuclear levels of NF-kappaB and to suppress NF-kappaB-mediated transcription, such as increased cytoplasmic and nuclear IkappaBalpha levels or decreased Bcl-3 levels, appeared to be induced. Nevertheless, even though counterregulatory mechanisms to NF-kappaB activation are activated in lung macrophages of patients with ARDS, NF-kappaB remains activated. These results suggest that fundamental abnormalities in transcriptional mechanisms involving NF-kappaB and important in the

  16. Modulating temporal control of NF-kappaB activation: implications for therapeutic and assay selection. (United States)

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


    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.

  17. Kappa-casein gene study in Iranian Sistani cattle breed (Bos indicus) using PCR-RFLP. (United States)

    Rohallah, Alinaghizadeh; Mohammadreza, Mohammad Abadi; Shahin, Moradnasab Badrabadi


    In cattle, caseins are subdivided into four main groups: alphaS1-, alphaaS2-, beta- and kappa-caseins. kappa-caseins (CSN2) considerably differ from other caseins in structure and other properties. Testing the A and B alleles is of practical importance, because the milk of cows that carry the B allele of CSN3 has a better thermal resistance and shorter coagulation time, better curdles and contains micelles of different sizes. Iranian Sistani cattle (Bos indicus) are a heavy built breed and used as dual-purpose cattle breed in Eastern Iran. This breed is a genetic resource that shows special features of adaptation to rustic environments. One of the most distinctive features of Sistani cattle is its great capability to resist diseases which makes it a potential reservoir of germplasm useful for future crosses. Our main goal was to study DNA-polymorphism of the CSN3 gene in the Iranian Sistani native cattle (Bos indicus) and analyze the information value of CSN3 gene polymorphism as a genetic marker. We genotyped and analyzed 65 animals of this breed using PCR-RFLP. The frequencies of A and B alleles were 0.6385 and 0.3615 and those of AA, AB and BB genotypes were 0.4000, 0.4769 and 0.1231, respectively. In the Sistani Zebu breed, frequency of B allele is higher than other Zebu breeds, indicating that intensive selection for dairy production have been done and indirectly influenced CSN3 allele frequencies.

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

    Energy Technology Data Exchange (ETDEWEB)

    Arshad, Kashif, E-mail:; Aman-ur-Rehman [Pakistan Institute of Engineering and Applied Sciences, P. O. Nilore, Islamabad 45650 (Pakistan); Mahmood, Shahzad [Pakistan Institute of Engineering and Applied Sciences, P. O. Nilore, Islamabad 45650 (Pakistan); Theoretical Physics Division, PINSTECH, P.O. Nilore, Islamabad 44000 (Pakistan)


    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)].

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

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


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

  20. Unconditioned behavioral effects of the powerful kappa-opioid hallucinogen salvinorin A in nonhuman primates: fast onset and entry into cerebrospinal fluid. (United States)

    Butelman, Eduardo R; Prisinzano, Thomas E; Deng, Haiteng; Rus, Szymon; Kreek, Mary Jeanne


    Salvinorin A is the main active component of the widely available hallucinogenic plant, Salvia divinorum. Salvinorin A is a selective high-efficacy kappa-agonist in vitro, with some unique pharmacodynamic properties. Descriptive reports show that salvinorin A-containing products produce robust behavioral effects in humans. However, these effects have not been systematically characterized in human or nonhuman primates to date. Therefore, the present studies focused on the characterization of overt effects of salvinorin A, such as sedation (operationally defined as unresponsiveness to environmental stimuli) and postural relaxation, previously observed with centrally penetrating kappa-agonists in nonhuman primates. Salvinorin A was active in these endpoints (dose range, 0.01-0.1 mg/kg i.v.) in nonhuman primates (n = 3-5), similar to the synthetic kappa-agonist U69,593 [(+)-(5alpha,7alpha,8beta)-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4.5]-dec-8-yl]-benzeneacetamide], used for comparison herein. Salvinorin A effects could be prevented by a clinically available opioid antagonist, nalmefene (0.1 mg/kg), at doses known to block kappa-receptor-mediated effects in nonhuman primates. When injected intravenously, salvinorin A (0.032 mg/kg) could enter the central nervous system (as reflected in cisternal cerebrospinal fluid) within 1 min and reach concentrations that are in the reported range of the affinity (K(i)) of this ligand for brain kappa-receptors. Consistent with this finding, specific translationally viable behavioral effects (e.g., facial relaxation and ptosis) could also be detected within 1 to 2 min of injection of salvinorin A. These are the first studies documenting rapid unconditioned effects of salvinorin A in a primate species, consistent with descriptive reports of rapid and robust effects of this powerful hallucinogen in humans.

  1. What Is the Critical Value of Glenoid Bone Loss at Which Soft Tissue Bankart Repair Does Not Restore Glenohumeral Translation, Restricts Range of Motion, and Leads to Abnormal Humeral Head Position? (United States)

    Shin, Sang-Jin; Koh, Yong Won; Bui, Christopher; Jeong, Woong Kyo; Akeda, Masaki; Cho, Nam Su; McGarry, Michelle H; Lee, Thay Q


    A general consensus has been formed that glenoid bone loss greater than 20% to 25% is the critical amount at which bony augmentation procedures are needed; however, recent clinical results suggest that the critical levels must be reconsidered to lower values. This study aimed to find the critical value of anterior glenoid bone loss when a soft tissue repair is not adequate to restore anterior-inferior glenohumeral translation, rotational range of motion, or humeral head position using a biomechanical anterior shoulder instability model. Controlled laboratory study. Eight cadaveric shoulders were tested with a customized shoulder testing system. Range of motion, translation, and humeral head position were measured at 60° of glenohumeral abduction in the scapular plane under a total of 40-N rotator cuff muscle loading in the following 11 conditions: intact; soft tissue Bankart lesion and repair; Bankart lesion with 10%, 15%, 20%, and 25% glenoid bone defects based on the largest anteroposterior width of the glenoid; and soft tissue Bankart repair for each respective glenoid defect. Serial osteotomies for each percentage of bone loss were made parallel to the long axis of the glenoid. There was significantly decreased external rotation (121.2° ± 2.8° to 113.5° ± 3.3°; P = .004), increased anteroinferior translation with an externally applied load (3.0 ± 1.2 mm to 7.5 ± 1.1 mm at 20 N; P = .008), and increased posterior (0.2 ± 0.6 mm to 2.7 ± 0.8 mm; P = .049) and inferior shift (2.9 ± 0.7 mm to 6.6 ± 1.1 mm; P = .018) of the humeral head apex in the position of maximum external rotation after soft tissue Bankart repair of a 15% glenoid defect compared with the repair of a Bankart lesion without a glenoid defect, respectively. Glenoid defects of 15% or more of the largest anteroposterior glenoid width should be considered the critical bone loss amount at which soft tissue repair cannot restore glenohumeral translation, restricts rotational range of motion

  2. Elevated expression of NF-kappaB in oral submucous fibrosis--evidence for NF-kappaB induction by safrole in human buccal mucosal fibroblasts. (United States)

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


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

  3. Investigation of the high-frequency attenuation parameter, κ (kappa), from aftershocks of the 2010 Mw 8.8 Maule, Chile earthquake (United States)

    Neighbors, Corrie; Liao, E. J.; Cochran, Elizabeth S.; Funning, G. J.; Chung, A. I.; Lawrence, J. F.; Christensen, C. M.; Miller, M.; Belmonte, A.; Sepulveda, H. H. Andrés


    The Bío Bío region of Chile experienced a vigorous aftershock sequence following the 2010 February 27 Mw 8.8 Maule earthquake. The immediate aftershock sequence was captured by two temporary seismic deployments: the Quake Catcher Network Rapid Aftershock Mobilization Program (QCN RAMP) and the Incorporated Research Institutions for Seismology CHile Aftershock Mobilization Program (IRIS CHAMP). Here, we use moderate to large aftershocks (ML ≥ 4.0) occurring between 2010 March 1 and June 30 recorded by QCN RAMP and IRIS CHAMP stations to determine the spectral decay parameter, kappa (κ). First, we compare waveforms and κ estimates from the lower-resolution QCN stations to the IRIS CHAMP stations to ensure the QCN data are of sufficient quality. We find that QCN stations provide reasonable estimates of κ in comparison to traditional seismic sensors and provide valuable additional observations of local ground motion variation. Using data from both deployments, we investigate the variation in κ for the region to determine if κ is influenced primarily by local geological structure, path attenuation, or source properties (e.g. magnitude, mechanism and depth). Estimates of κ for the Bío Bío region range from 0.0022 to 0.0704 s with a mean of 0.0295 s and are in good agreement with κ values previously reported for similar tectonic environments. κ correlates with epicentral distance and, to a lesser degree, with source magnitude. We find little to no correlation between the site kappa, κ0, and mapped geology, although we were only able to compare the data to a low-resolution map of surficial geology. These results support an increasing number of studies that suggest κobservations can be attributed to a combination of source, path and site properties; additionally, measured κ are often highly scattered making it difficult to separate the contribution from each of these factors. Thus, our results suggest that contributions from the site

  4. SANS study of surfactant ordering in kappa-carrageenan/cetylpyridinium chloride complexes

    DEFF Research Database (Denmark)

    Evmenenko, G.; Theunissen, E.; Mortensen, K.


    Small-angle neutron scattering using contrast variation by H2O/D2O has been applied for the structural investigation of kappa -carrageenan/cetylpyridinium chloride (CPC) complexes. interaction of kappa -carrageenan with an ionic surfactant involves self-assembly of the surfactant molecules...

  5. Polymorphisms in NF-kappa B, PXR, LXR, PPAR gamma and risk of inflammatory bowel disease

    DEFF Research Database (Denmark)

    Andersen, Vibeke; Christensen, Jane; Ernst, Anja


    AIM: To investigate the contribution of polymorphisms in nuclear receptors to risk of inflammatory bowel disease (IBD). METHODS: Genotypes of nuclear factor (NF)-kappa B (NFKB1) NF kappa B -94ins/del (rs28362491); peroxisome proliferator-activated receptor (PPAR)-gamma (PPAR gamma) PPAR gamma Pro12...

  6. Good cop, bad cop: the different faces of NF-kappaB. (United States)

    Perkins, N D; Gilmore, T D


    Complexes formed from the nuclear factor kappaB (NF-kappaB) family of transcription factors are ubiquitously expressed and are induced by a diverse array of stimuli. This results in their becoming activated in a wide variety of different settings. While the functions of NF-kappaB in many of these contexts have been the subject of intense research and are now well established, it is also clear that there is great diversity in the effects and consequences of NF-kappaB activation. NF-kappaB subunits do not necessarily regulate the same genes, in an identical manner, in all of the different circumstances in which they are induced. This review will discuss the different functions of NF-kappaB, the pathways that modulate NF-kappaB subunit activity and, in contrast to its more commonly thought of role as a promoter of cancer cell growth and survival, the ability of NF-kappaB, under some circumstances, to behave as a tumor suppressor.

  7. Mitochondria mediate tumor necrosis factor-alpha/NF-kappaB signaling in skeletal muscle myotubes (United States)

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


    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.

  8. DMPD: Shared principles in NF-kappaB signaling. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18267068 Shared principles in NF-kappaB signaling. Hayden MS, Ghosh S. Cell. 2008 F...eb 8;132(3):344-62. (.png) (.svg) (.html) (.csml) Show Shared principles in NF-kappaB signaling. PubmedID 18267068 Title Shared

  9. The Value of Value

    DEFF Research Database (Denmark)

    Sørensen, Asger

    parts of business ethics given prominence to especially one term, namely `value'. The question that interests me is the following: What does the articulation of ethics and morality in terms of values mean for ethics and morality as such. Or, to put the question in a more fashionably way: What...... is the value of value for morality and ethics?To make things a bit more precise, we can make use of the common distinction between ethics and morality, i.e. that morality is the immediate, collective and unconscious employment of morals, whereas ethics is the systematic, individual and conscious reflections...

  10. Range Tracing


    Jenke, Philipp; Huhle, Benjamin


    In this report, we tackle the problem of merging an arbitrary number of range scans (depth images) into a single surface mesh. The mesh-based representation is superior to point-based approaches since it contains important connectivity information. Most previous mesh-based merge methods, however, lose surface details by using simplifying intermediate surface representations (e.g.\\ implicit functions). Such details are essential for further processing steps, especially for feature-preserving r...

  11. Relative locality in a quantum spacetime and the pregeometry of $\\kappa$-Minkowski

    CERN Document Server

    Amelino-Camelia, Giovanni; Rosati, Giacomo


    We develop a new description of the much-studied $\\kappa$-Minkowski noncommutative spacetime, centered on representing on a single Hilbert space not only the $\\kappa$-Minkowski coordinates, but also the associated differential calculus and the $\\kappa$-Poincar\\'e symmetry generators. In this "pregeometric" representation the relevant operators act on the kinematical Hilbert space of the covariant formulation of quantum mechanics, which we argue is the natural framework for studying the implications of the step from commuting spacetime coordinates to the $\\kappa$-Minkowski case, where the spatial coordinates do not commute with the time coordinate. The empowerment provided by this kinematical-Hilbert space representation allows us to give a crisp characterization of the "fuzziness" of $\\kappa$-Minkowski spacetime, whose most striking aspect is a relativity of spacetime locality. We show that relative locality, which had been previously formulated exclusively in classical-spacetime setups, for a quantum spaceti...

  12. $\\kappa$-deformed Landau levels and implications on the integer quantum Hall effect

    CERN Document Server

    Andrade, Fabiano M; Assafrão, Denise; Filgueiras, Cleverson


    In this letter the $\\kappa$-deformed Dirac equation is used to study the relativistic generalization of the $\\kappa$-deformed Landau levels and the consequences of the deformation on the Hall conductivity. The isolated solutions for the first order differential equations, excluded from the Sturm-Liouville problem, are investigated. They do exist, but are independent of the deformation parameter. An expression for the $\\kappa$-deformed relativistic Landau levels is obtained. It is observed that the deformation parameter breaks the Landau levels degeneracy. Considering the $\\kappa$-deformed Landau levels in the nonrelativistic regime the Hall conductivity of a two-dimensional electron system is obtained. The expression obtained recovers the well-known result for the usual Hall conductivity in the limit $\\varepsilon=\\kappa^{-1}\\to 0$. It is also observed that deformation generates new plateaus of conductivity in a such way that the plateaus widths of the deformed system are less than the undeformed one.

  13. Relationship between the Expression of NF-kappa B and Apoptosis in Non-Small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    Jianqun Ma; Zhenfa Zhang; Shidong Xu


    OBJECTIVE To study the expression of the nuclear factor kappa B (NF-kappa B)in non-small cell lung cancer(NSCLC),to explore the apoptotic ratio in NSCLC related to different NF-kappa Bs,and to understand the clinical significance of NF-kappa B in NSCLC apoptosis.METHODS NF-kappa B expression in 45 new samples of NSCLC,collected during a period from October to December,2005,was assayed using Western blots,and the apoptotic ratio of NSCLC was determined by the Tunel method.RESULTS Of the 45 patients,the average relative expressxon of NF-kappa B was 0.6047±0.3572.The expression of NF-kappa B was higher in the poorly differentiated lung cancer cells than in the well-differentiated tumors (P<0.05).The apoptotic ratio was 56.4%in the lung cancer cells with higher NF-kappa B expression,and was 76.7%in those with lower NF-kappa B expression(P<0.05).CONCLUSION The expression of NF-kappa B is correlated with the differentiation of NSCLC.NF-kappa B inhibits apoptosis in NSCLC.AS a transcription factor,NF-kappa B plays a very important role both in formation and in development of NSCLC.NF-kappa B might serve as a target for NSCLC gene therapy.

  14. Adding value(s)

    DEFF Research Database (Denmark)

    Carré, David


    , 1992). In response, behavioral economics (Camerer, 1999) has shown that agents have values other than optimization underpinning their decisions. Therefore, concerns arose regarding which values are guiding the agent but not about how such values became relevant for the agent. In this presentation, I......Most economic inquires revolve around agents making decisions. Getting the ‘best value’, it is assumed, drives such decisions: gaining most while risking least. This assumption has been debunked by showing that people does not always choose neither maximum benefit nor less risk (Kahneman & Tversky...... will explore the consequences of shifting to the latter perspective, i.e. looking for the generative framework of values. Here I argue that economic behavior should also be seen as a sense-making process, guided by values that are chosen/rejected along with fellow human beings, in specific socio...

  15. Statistics of assay validation in high throughput cell imaging of nuclear factor kappaB nuclear translocation. (United States)

    Morelock, Maurice M; Hunter, Edward A; Moran, Timothy J; Heynen, Susanne; Laris, Casey; Thieleking, Michael; Akong, Michael; Mikic, Ivana; Callaway, Scott; DeLeon, Rodney P; Goodacre, Angela; Zacharias, David; Price, Jeffrey H


    This report describes statistical validation methods implemented on assay data for inhibition of subcellular redistribution of nuclear factor kappaB (NF kappaB) in HeLa cells. We quantified cellular inhibition of cytoplasmic-nuclear translocation of NF kappaB in response to a range of concentrations of interleukin-1 (IL-1) receptor antagonist in the presence of IL-1alpha using eight replicate rows in each four 96-well plates scanned five times on each of 2 days. Translocation was measured as the fractional localized intensity of the nucleus (FLIN), an implementation of our more general fractional localized intensity of the compartments (FLIC), which analyzes whole compartments in the context of the entire cell. The NF kappaB antagonist assay (inhibition of IL-1- induced NF kappaB translocation) data were collected on a Q3DM (San Diego, CA) EIDAQtrade mark 100 high throughput microscopy system. [In 2003, Q3DM was purchased by Beckman Coulter Inc. (Fullerton, CA), which released the IC 100 successor to the EIDAQ 100.] The generalized FLIC method is described along with two-point (minimum-maximum) and multiple point titration statistical methods. As a ratio of compartment intensities that tend to change proportionally, FLIN was resistant to photobleaching errors. Two-point minimum-maximum statistical analyses yielded the following: a Z' of 0.174 with the data as n = 320 independent well samples; Z' by row data in a range of 0.393-0.933, with a mean of 0.766; by-plate Z' data of 0.310, 0.443, 0.545, and 0.794; and by-plate means of columns Z' data of 0.879, 0.927, 0.945, and 0.963. The mean 50% inhibitory concentration (IC50) for IL-1 receptor antagonist over all experiments was 213 ng/ml. The combined IC50 coefficients of variation (CVs) were 0.74%, 0.85%, 2.09%, and 2.52% for the four plates. Repeatability IC50 CVs were as follows: day to day 3.0%, row to row 8.0%, plate to plate 2.8%, and day to day 0.6%. The number of cells required for statistically resolvable

  16. Requirement of NF-kappaB/Rel for the development of hair follicles and other epidermal appendices. (United States)

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


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

  17. Rare and Common Variants in CARD14, Encoding an Epidermal Regulator of NF-kappaB, in Psoriasis (United States)

    Jordan, Catherine T.; Cao, Li; Roberson, Elisha D.O.; Duan, Shenghui; Helms, Cynthia A.; Nair, Rajan P.; Duffin, Kristina Callis; Stuart, Philip E.; Goldgar, David; Hayashi, Genki; Olfson, Emily H.; Feng, Bing-Jian; Pullinger, Clive R.; Kane, John P.; Wise, Carol A.; Goldbach-Mansky, Raphaela; Lowes, Michelle A.; Peddle, Lynette; Chandran, Vinod; Liao, Wilson; Rahman, Proton; Krueger, Gerald G.; Gladman, Dafna; Elder, James T.; Menter, Alan; Bowcock, Anne M.


    Psoriasis is a common inflammatory disorder of the skin and other organs. We have determined that mutations in CARD14, encoding a nuclear factor of kappa light chain enhancer in B cells (NF-kB) activator within skin epidermis, account for PSORS2. Here, we describe fifteen additional rare missense variants in CARD14, their distribution in seven psoriasis cohorts (>6,000 cases and >4,000 controls), and their effects on NF-kB activation and the transcriptome of keratinocytes. There were more CARD14 rare variants in cases than in controls (burden test p value = 0.0015). Some variants were only seen in a single case, and these included putative pathogenic mutations (c.424G>A [p.Glu142Lys] and c.425A>G [p.Glu142Gly]) and the generalized-pustular-psoriasis mutation, c.413A>C (p.Glu138Ala); these three mutations lie within the coiled-coil domain of CARD14. The c.349G>A (p.Gly117Ser) familial-psoriasis mutation was present at a frequency of 0.0005 in cases of European ancestry. CARD14 variants led to a range of NF-kB activities; in particular, putative pathogenic variants led to levels >2.5× higher than did wild-type CARD14. Two variants (c.511C>A [p.His171Asn] and c.536G>A [p.Arg179His]) required stimulation with tumor necrosis factor alpha (TNF-α) to achieve significant increases in NF-kB levels. Transcriptome profiling of wild-type and variant CARD14 transfectants in keratinocytes differentiated probably pathogenic mutations from neutral variants such as polymorphisms. Over 20 CARD14 polymorphisms were also genotyped, and meta-analysis revealed an association between psoriasis and rs11652075 (c.2458C>T [p.Arg820Trp]; p value = 2.1 × 10−6). In the two largest psoriasis cohorts, evidence for association increased when rs11652075 was conditioned on HLA-Cw∗0602 (PSORS1). These studies contribute to our understanding of the genetic basis of psoriasis and illustrate the challenges faced in identifying pathogenic variants in common disease. PMID:22521419

  18. Curcumin protects against acute liver damage in the rat by inhibiting NF-kappaB, proinflammatory cytokines production and oxidative stress. (United States)

    Reyes-Gordillo, Karina; Segovia, José; Shibayama, Mineko; Vergara, Paula; Moreno, Mario G; Muriel, Pablo


    Curcumin, an anti-inflammatory and antioxidant compound, was evaluated for its ability to suppress acute carbon tetrachloride-induced liver damage. Acute hepatotoxicity was induced by oral administration of CCl4 (4 g/kg, p.o.). Curcumin treatment (200 mg/kg, p.o.) was given before and 2 h after CCl4 administration. Indicators of necrosis (alanine aminotransferase) and cholestasis (gamma-glutamyl transpeptidase and bilirubins) resulted in significant increases after CCl4 intoxication, but these effects were prevented by curcumin treatment. As an indicator of oxidative stress, GSH was oxidized and the GSH/GSSG ratio decreased significantly by CCl4, but was preserved within normal values by curcumin. In addition to its antioxidants properties, curcumin is capable of preventing NF-kappaB activation and therefore to prevent the secretion of proinflammatory cytokines. Therefore, in this study we determined the concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6) mRNA, and NF-kappaB activation. CCl4-administered rats depicted significant increases in TNF-alpha, IL-1beta, and IL-6 production, while curcumin remarkably suppressed these mediators of inflammation in liver damage. These results were confirmed by measuring TNF-alpha, and IL-1beta protein production using Western Blot analysis. Accordingly, these proteins were increased by CCl4 and this effect was abolished by curcumin. Administration of CCl4 induced the translocation of NF-kappaB to the nucleus; CCl4 induced NF-kappaB DNA binding activity was blocked by curcumin treatment. These findings suggest that curcumin prevents acute liver damage by at least two mechanisms: acting as an antioxidant and by inhibiting NF-kappaB activation and thus production of proinflammatory cytokines.

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

    Energy Technology Data Exchange (ETDEWEB)

    Santos, M. S. dos, E-mail: [Instituto de Física, Universidade Federal do Rio Grande do Sul, 91501-970, Porto Alegre, RS (Brazil); Instituto Federal de Educação, Ciência e Tecnologia Farroupilha, 98590-000, Santo Augusto, RS (Brazil); Ziebell, L. F., E-mail:; Gaelzer, R., E-mail: [Instituto de Física, Universidade Federal do Rio Grande do Sul, 91501-970, Porto Alegre, RS (Brazil)


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

  20. DMPD: Ubiquitin: tool and target for intracellular NF-kappaB inhibitors. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16982211 Ubiquitin: tool and target for intracellular NF-kappaB inhibitors. (.html) (.csml) Show Ubiquitin: tool and target for intracellular NF-kappaB inhibitors. PubmedID 1698221...1 Title Ubiquitin: tool and target for intracellular NF-kappaB inhibitors. Author

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

    Energy Technology Data Exchange (ETDEWEB)

    Genetos, Damian C., E-mail: [Department of Anatomy, Cell Biology, and Physiology, School of Veterinary Medicine, University of California, Davis, CA (United States); Karin, Norman J. [Cell Biology and Biochemistry, Pacific Northwest National Laboratory, Richland, WA (United States); Geist, Derik J. [Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN (United States); Donahue, Henry J. [Division of Musculoskeletal Sciences, Department of Orthopaedics and Rehabilitation, Pennsylvania State College of Medicine, Hershey, PA (United States); Duncan, Randall L. [Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN (United States)


    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.

  2. DMPD: NF-kappaB activation by reactive oxygen species: fifteen years later. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16723122 NF-kappaB activation by reactive oxygen species: fifteen years later. Gloi...svg) (.html) (.csml) Show NF-kappaB activation by reactive oxygen species: fifteen years later. PubmedID 167...23122 Title NF-kappaB activation by reactive oxygen species: fifteen years later.

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

    Energy Technology Data Exchange (ETDEWEB)

    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. (VCU); (Scripps); (UNC); (Res. Tri. Inst.)


    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.

  4. Modulation of the NF-kappaB pathway by Bordetella pertussis filamentous hemagglutinin.

    Directory of Open Access Journals (Sweden)

    Tzvia Abramson

    Full Text Available BACKGROUND: Filamentous hemagglutinin (FHA is a cell-associated and secreted adhesin produced by Bordetella pertussis with pro-apoptotic and pro-inflammatory activity in host cells. Given the importance of the NF-kappaB transcription factor family in these host cell responses, we examined the effect of FHA on NF-kappaB activation in macrophages and bronchial epithelial cells, both of which are relevant cell types during natural infection. METHODOLOGY/PRINCIPAL FINDINGS: Exposure to FHA of primary human monocytes and transformed U-937 macrophages, but not BEAS-2B epithelial cells, resulted in early activation of the NF-kappaB pathway, as manifested by the degradation of cytosolic IkappaB alpha, by NF-kappaB DNA binding, and by the subsequent secretion of NF-kappaB-regulated inflammatory cytokines. However, exposure of macrophages and human monocytes to FHA for two hours or more resulted in the accumulation of cytosolic IkappaB alpha, and the failure of TNF-alpha to activate NF-kappaB. Proteasome activity was attenuated following exposure of cells to FHA for 2 hours, as was the nuclear translocation of RelA in BEAS-2B cells. CONCLUSIONS: These results reveal a complex temporal dynamic, and suggest that despite short term effects to the contrary, longer exposures of host cells to this secreted adhesin may block NF-kappaB activation, and perhaps lead to a compromised immune response to this bacterial pathogen.

  5. Prefrontal Cortical Kappa Opioid Receptors Attenuate Responses to Amygdala Inputs. (United States)

    Tejeda, Hugo A; Hanks, Ashley N; Scott, Liam; Mejias-Aponte, Carlos; Hughes, Zoë A; O'Donnell, Patricio


    Kappa opioid receptors (KORs) have been implicated in anxiety and stress, conditions that involve activation of projections from the basolateral amygdala (BLA) to the medial prefrontal cortex (mPFC). Although KORs have been studied in several brain regions, their role on mPFC physiology and on BLA projections to the mPFC remains unclear. Here, we explored whether KORs modify synaptic inputs from the BLA to the mPFC using in vivo electrophysiological recordings with electrical and optogenetic stimulation. Systemic administration of the KOR agonist U69,593 inhibited BLA-evoked synaptic responses in the mPFC without altering hippocampus-evoked responses. Intra-mPFC U69,593 inhibited electrical and optogenetic BLA-evoked synaptic responses, an effect blocked by the KOR antagonist nor-BNI. Bilateral intra-mPFC injection of the KOR antagonist nor-BNI increased center time in the open field test, suggesting an anxiolytic effect. The data demonstrate that mPFC KORs negatively regulate glutamatergic synaptic transmission in the BLA-mPFC pathway and anxiety-like behavior. These findings provide a framework whereby KOR signaling during stress and anxiety can regulate the flow of emotional state information from the BLA to the mPFC.

  6. NF-kappaB Signaling in Chronic Inflammatory Airway Disease

    Directory of Open Access Journals (Sweden)

    Michael Schuliga


    Full Text Available Asthma and chronic obstructive pulmonary disease (COPD are obstructive airway disorders which differ in their underlying causes and phenotypes but overlap in patterns of pharmacological treatments. In both asthma and COPD, oxidative stress contributes to airway inflammation by inducing inflammatory gene expression. The redox-sensitive transcription factor, nuclear factor (NF-kappaB (NF-κB, is an important participant in a broad spectrum of inflammatory networks that regulate cytokine activity in airway pathology. The anti-inflammatory actions of glucocorticoids (GCs, a mainstay treatment for asthma, involve inhibition of NF-κB induced gene transcription. Ligand bound GC receptors (GRs bind NF-κB to suppress the transcription of NF-κB responsive genes (i.e., transrepression. However, in severe asthma and COPD, the transrepression of NF-κB by GCs is negated as a consequence of post-translational changes to GR and histones involved in chromatin remodeling. Therapeutics which target NF-κB activation, including inhibitors of IκB kinases (IKKs are potential treatments for asthma and COPD. Furthermore, reversing GR/histone acetylation shows promise as a strategy to treat steroid refractory airway disease by augmenting NF-κB transrepression. This review examines NF-κB signaling in airway inflammation and its potential as target for treatment of asthma and COPD.

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

    Directory of Open Access Journals (Sweden)

    Catherine M Cahill


    Full Text Available 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.

  8. Application of Kappa (κ) index in clinical training for eight-year program medical students%应用Kappa(κ)指数辅助长学制妇产科临床技能培训的研究

    Institute of Scientific and Technical Information of China (English)

    赵超; 田莉; 刘春兰; 王建六; 魏丽惠


    Objective To screened out items with large proportion of technical analysis in obstetrics and gynecology physical examination by using statistical parameters Kappa index and to evaluate effect and clinical significance of Kappa index based on objective data and students' and teachers' subjective feeling.Methods We made Kappa index screening with double-blind method and established the Kappa index table for teachers and students.Students were randomly divided into conventional teaching group (n =26) and teaching reform group (n =29).Students in conventional teaching group traditionally followed the teacher to carry on the practice while those in teaching reform group received training according to the numerical value index and had examination after training.We paid attention to each student's weak points,provided personalized guidance and communicated with students actively.Results We found that it was uneasy for beginners to quickly grasp four step obstetrics palpation in-spection according to Kappa index.There were statistical differences in operation of gynecological physical examination between two groups (P =0.016).Conclusions Application of Kappa index can help us screen out skills in the operation suitable for training for eight-year program medical students.With quantitative evaluation,we can improve quality of clinical practice teaching in department of obstetrics and gynecology and guide educational reform.%目的 运用统计学参数Kappa指数筛查出妇产科专科体检和操作中技术因素比重较大的体检项目,根据客观数据,结合学生与教师的主观感受综合评价Kappa指数应用于长学制妇产科临床教学的效果和意义.方法 应用双盲法对妇产科专科体检和操作分项目进行Kappa指数筛查.建立教师水平体检操作的Kappa指数表,并对首轮实习的长学制医学生建立Kappa指数表.将实习医学生随机分为常规教学组(26人)及教改组(29人).常规教学组按照传统跟随

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

    Energy Technology Data Exchange (ETDEWEB)

    Hachem, Ahmed [Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, 5000 Belanger, Montreal, Quebec, Canada H1T 1C8 (Canada); Yacoub, Daniel [Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, 5000 Belanger, Montreal, Quebec, Canada H1T 1C8 (Canada); Centre Hospitalier Universite de Montreal, 264 boul. Rene-Levesque est, Montreal, Quebec, Canada H2X 1P1 (Canada); Zaid, Younes [Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, 5000 Belanger, Montreal, Quebec, Canada H1T 1C8 (Canada); Mourad, Walid [Universite de Montreal, Department of Medicine, 2900 boul. Edouard-Montpetit, Montreal, Quebec, Canada H3T 1J4 (Canada); Centre Hospitalier Universite de Montreal, 264 boul. Rene-Levesque est, Montreal, Quebec, Canada H2X 1P1 (Canada); Merhi, Yahye, E-mail: [Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, 5000 Belanger, Montreal, Quebec, Canada H1T 1C8 (Canada); Universite de Montreal, Department of Medicine, 2900 boul. Edouard-Montpetit, Montreal, Quebec, Canada H3T 1J4 (Canada)


    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

  10. kappa+lambda+ dual receptor B cells are present in the human peripheral repertoire



    It is a common notion that mature B lymphocytes express either kappa or lambda light (L) chains, although the mechanism that leads to such isotypic exclusion is still debated. We have investigated the extent of L chain isotypic exclusion in normal human peripheral blood B lymphocytes. By three-color staining with anti-CD19, anti-kappa, and anti-lambda antibodies we could estimate that 0.2-0.5% of peripheral blood B cells from healthy adults express both kappa and lambda on the cell surface. T...

  11. Some Features of Scattering Problem in a $\\kappa$-Deformed Minkowski Spacetime

    CERN Document Server

    Khodadi, Mohsen


    The doubly special relativity (DSR) theories are suggested in order to incorporate an observer-independent length scale in special theory of relativity. The Magueijo-Smolin proposal of DSR is realizable through a particular form of the noncommutative (NC) spacetime (known as $\\kappa$-Minkowski spacetime) in which the Lorentz symmetry is preserved. In this framework, the NC parameter $\\kappa$ provides the origin of natural cutoff energy scale. Using a nonlinear deformed relativistic dispersion relation along with the Lorentz transformations, we investigate some phenomenological facets of two-body collision problem (without creation of new particles) in a $\\kappa$-Minkowski spacetime. By treating an elastic scattering problem, we study effects of the Planck scale energy cutoff on some relativistic kinematical properties of this scattering problem. The results are challenging in the sense that as soon as one turns on the $\\kappa$-spacetime extension, the nature of the two-body collision alters from elastic to in...

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

    CERN Document Server

    Nicolaou, Georgios


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

  13. Whistler-Mode Waves Growth by a Generalized Relativistic Kappa-Type Distribution

    Institute of Scientific and Technical Information of China (English)

    ZHOU Qing-Hua; JIANG Bin; SHI Xiang-Hua; LI Jun-Qiu


    The instability of field-aligned Whistler-mode waves in space plasmas is studied by using a recently developed generalized relativistic kappa-type (KT) distribution. Numerical calculations are performed for a direct compar-ison between the new KT distribution and the current kappa distribution. We show that the wave growth for the KT distribution tends to occur in the lower wave frequency (e.g., ω 0.1Ωe) due to a larger fractional num-ber of the resonant electrons ηrel (which controls the wave growth), while primarily locating in the higher wave frequency for the kappa distribution. Moreover, the relativistic anisotropy Arel by the KT distribution is found to be smaller than that by the kappa distribution, leading to a smaller peak of wave growth. The results present a further understanding of plasma wave instability particularly in those plasmas where relativistic electrons are present.

  14. Requirement for caspase-8 in NF-kappaB activation by antigen receptor. (United States)

    Su, Helen; Bidère, Nicolas; Zheng, Lixin; Cubre, Alan; Sakai, Keiko; Dale, Janet; Salmena, Leonardo; Hakem, Razqallah; Straus, Stephen; Lenardo, Michael


    Caspase-8, a proapoptotic protease, has an essential role in lymphocyte activation and protective immunity. We show that caspase-8 deficiency (CED) in humans and mice specifically abolishes activation of the transcription factor nuclear factor kappaB (NF-kappaB) after stimulation through antigen receptors, Fc receptors, or Toll-like receptor 4 in T, B, and natural killer cells. Caspase-8 also causes the alphabeta complex of the inhibitor of NF-kappaB kinase (IKK) to associate with the upstream Bcl10-MALT1 (mucosa-associated lymphatic tissue) adapter complex. Recruitment of the IKKalpha, beta complex, its activation, and the nuclear translocation of NF-kappaB require enzyme activity of full-length caspase-8. These findings thus explain the paradoxical association of defective apoptosis and combined immunodeficiency in human CED.

  15. A gut feeling of the PXR, PPAR and NF-kappaB connection. (United States)

    Wahli, W


    Bowel diseases reveal the complex interplay of sensing and signalling pathways in maintaining healthy homeostasis of the intestine. Recent studies of the xenobiotic nuclear receptor, pregnane X receptor and the inflammatory mediator nuclear transcription factor kappaB (NF-kappaB) reveal a functional link between xenobiotic neutralization and inflammation and explain how certain xenobiotics can affect the immune response. Furthermore, another nuclear receptor, peroxisome proliferator-activated receptor gamma (PPAR gamma) has been shown to produce beneficial effects in experimental inflammatory bowel diseases by repression of NF-kappaB thereby reducing inflammation, whilst its close relative PPAR beta/delta appears at a central position in signalling pathways involved in the progression of colon cancer. Recently accumulated knowledge on the action of these nuclear receptors and NF-kappaB in intestinal homeostasis may provide the rationale for the development of innovative treatment strategies with selective receptor modulators.

  16. Twist deformations leading to kappa-Poincare Hopf algebra and their application to physics

    CERN Document Server

    Jurić, Tajron; Samsarov, Andjelo


    We consider two twist operators that lead to kappa-Poincare Hopf algebra, the first being an Abelian one and the second corresponding to a light-like kappa-deformation of Poincare algebra. The advantage of the second one is that it is expressed solely in terms of Poincare generators. In contrast to this, the Abelian twist goes out of the boundaries of Poincare algebra and runs into envelope of the general linear algebra. Some of the physical applications of these two different twist operators are considered. In particular, we use the Abelian twist to construct the statistics flip operator compatible with the action of deformed symmetry group. Furthermore, we use the light-like twist operator to define a star product and subsequently to formulate a free scalar field theory compatible with kappa-Poincare Hopf algebra and appropriate for considering the interacting phi^4 scalar field model on kappa-deformed space.

  17. A new low molecular weight heparan sulphate antagonizes kappa-carrageenan-induced thrombosis in rats. (United States)

    Gervasi, G B; Bartoli, C; Carpita, G


    Kappa-carrageenan (kappa-carrageenin; kappa-carragheen) was found to be thrombogenic in rats. After i.p. injection of 3 mg/kg of kappa-carrageenan the thrombosis extended to a maximum 7.5 cm from the tip of the tail. Infarction frequency as well as the extent of infarction were inhibited by oral administration of a new heparan sulphate of low molecular weight (LMW-HS) (alpha-idosane). Mesoglycan and heparin were active when administered by parenteral route, and aspirin showed no effect; mesoglycan was inactive at 50 mg/kg per os. The present data confirm the validity of this experimental model for evaluating the protective effects of antithrombotic drugs and show the activity of oral administration of a new drug endowed with fibrinolytic activity.

  18. Arenavirus nucleoproteins prevent activation of nuclear factor kappa B. (United States)

    Rodrigo, W W Shanaka I; Ortiz-Riaño, Emilio; Pythoud, Christelle; Kunz, Stefan; de la Torre, Juan C; Martínez-Sobrido, Luis


    Arenaviruses include several causative agents of hemorrhagic fever (HF) disease in humans that are associated with high morbidity and significant mortality. Morbidity and lethality associated with HF arenaviruses are believed to involve the dysregulation of the host innate immune and inflammatory responses that leads to impaired development of protective and efficient immunity. The molecular mechanisms underlying this dysregulation are not completely understood, but it is suggested that viral infection leads to disruption of early host defenses and contributes to arenavirus pathogenesis in humans. We demonstrate in the accompanying paper that the prototype member in the family, lymphocytic choriomeningitis virus (LCMV), disables the host innate defense by interfering with type I interferon (IFN-I) production through inhibition of the interferon regulatory factor 3 (IRF3) activation pathway and that the viral nucleoprotein (NP) alone is responsible for this inhibitory effect (C. Pythoud, W. W. Rodrigo, G. Pasqual, S. Rothenberger, L. Martínez-Sobrido, J. C. de la Torre, and S. Kunz, J. Virol. 86:7728-7738, 2012). In this report, we show that LCMV-NP, as well as NPs encoded by representative members of both Old World (OW) and New World (NW) arenaviruses, also inhibits the nuclear translocation and transcriptional activity of the nuclear factor kappa B (NF-κB). Similar to the situation previously reported for IRF3, Tacaribe virus NP (TCRV-NP) does not inhibit NF-κB nuclear translocation and transcriptional activity to levels comparable to those seen with other members in the family. Altogether, our findings demonstrate that arenavirus infection inhibits NF-κB-dependent innate immune and inflammatory responses, possibly playing a key role in the pathogenesis and virulence of arenavirus.

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

    Energy Technology Data Exchange (ETDEWEB)

    Woods, Dori C., E-mail: [Vincent Center for Reproductive Biology, Vincent Obstetrics and Gynecology Service, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02114 (United States); White, Yvonne A.R. [Vincent Center for Reproductive Biology, Vincent Obstetrics and Gynecology Service, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02114 (United States); Dau, Caroline [University of California, San Francisco, School of Dentistry, San Francisco, CA 94143 (United States); Johnson, A.L. [Center for Reproductive Biology and Health, The Pennsylvania State University, University Park, PA 16802 (United States)


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

  20. Subadditive withdrawal from cocaine/kappa-opioid agonist combinations in Planaria. (United States)

    Raffa, Robert B; Stagliano, Gregory W; Tallarida, Ronald J


    We have previously developed and extensively characterized a convenient and sensitive metric for the quantification of withdrawal responses using Planaria. Planaria are particularly valuable for these studies because of their permeable exteriors and their relevant neurotransmitter systems (e.g., dopaminergic, opioid, and serotonergic). In the present study, we used this metric and mathematically rigorous joint-action analysis to investigate poly-drug withdrawal from fixed-ratio cocaine/kappa-opioid agonist combinations. The D50 (concentration producing half-maximal effect) for cocaine and U-50,488H was 10.3 and 1.02 microg, respectively. The D50 for 19:1 or 1:19 combinations did not differ significantly (p>0.05) from expected additive values (11.6+/-3.0 vs. 9.9+/-1.4 and 1.1+/-0.2 vs. 1.5+/-0.1, respectively), but the 3:1, 1:1, and 1:3 ratios did (34.5+/-6.9 vs. 7.7+/-1.1; 55.1+/-10.0 vs. 5.7+/-0.7; and 40.8+/-8.9 vs. 3.3+/-0.4, respectively), indicating subadditive interaction at these ratios. The finding of subadditivity in this model suggests that abstinence-induced withdrawal from the combination is less intense than that predicted from the individual drug potencies. The concept that certain combinations of drugs leads to attenuated withdrawal might generalize to humans.

  1. The Age of the Directly-Imaged Planet Host Star $\\kappa$ Andromedae Determined From Interferometric Observations

    CERN Document Server

    Jones, Jeremy; Quinn, S; Ireland, M; Boyajian, T; Schaefer, G; Baines, E K


    $\\kappa$ Andromedae, an early type star that hosts a directly imaged low mass companion, is expected to be oblate due to its rapid rotational velocity ($v\\sin i$ = $\\sim$162 $\\mathrm{km~s^{-1}}$). We observed the star with the CHARA Array's optical beam combiner, PAVO, measuring its size at multiple orientations and determining its oblateness. The interferometric measurements, combined with photometry and this $v\\sin i$ value are used to constrain an oblate star model that yields the fundamental properties of the star and finds a rotation speed that is $\\sim$85\\% of the critical rate and a low inclination of $\\sim$30$^\\circ$. Three modeled properties (the average radius, bolometric luminosity, and equatorial velocity) are compared to MESA evolution models to determine an age and mass for the star. In doing so, we determine an age for the system of 47$^{+27}_{-40}$ Myr. Based on this age and previous measurements of the companion's temperature, the BHAC15 evolution models imply a mass for the companion of 22$^...

  2. Receptor activator of nuclear factor kappa B (RANK as a determinant of peri-implantitis

    Directory of Open Access Journals (Sweden)

    Rakić Mia


    Full Text Available Background/Aim. Peri-implantitis presents inflammatory process that affects soft and hard supporting tissues of osseointegrated implant based on inflammatory osteoclastogenesis. The aim of this study was to investigate whether receptor activator of nuclear factor kappa B (RANK concentrations in peri-implant crevicular fluid could be associated with clinical parameters that reflect inflammatory nature of peri-implantitis. Methods. The study included 67 patients, 22 with diagnosed peri-implantitis, 22 persons with healthy peri-implant tissues and 23 patients with periodontitis. Clinical parameters from each patient were recorded and samples of peri-implant/gingival crevicular fluid were collected for the enzyme-linked immunosorbent assay (ELISA analysis. Results. RANK concentration was significantly increased in samples from the patients with periimplantitis when compared to healthy implants (p < 0.0001, where the average levels were 9 times higher. At the same time RANK concentration was significantly higher in periimplantitis than in periodontitis sites (p < 0.0001. In implant patients pocket depths and bleeding on probing values were positively associated with high RANK concentrations (p < 0.0001. Conclusion. These results revealed association of increased RANK concentration in samples of periimplant/ gingival crevicular fluid with peri-implant inflammation and suggests that RANK could be a pathologic determinant of peri-implantitis, thereby a potential parameter in assessment of peri-implant tissue inflammation and a potential target in designing treatment strategies.

  3. Resistivity investigations on the X-ray irradiated Mott insulator {kappa}-(ET){sub 2}Cu[N(CN){sub 2}]Cl

    Energy Technology Data Exchange (ETDEWEB)

    Naji, Ammar; Tutsch, Ulrich; Lang, Michael [Physikalisches Institut, Goethe-Universitaet Frankfurt (M), SFB/TRR49, D-60438 Frankfurt am Main (Germany); Sasaki, Takahiko [Institute for Material Research, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai, Miyagi 980-8577 (Japan)


    The compound {kappa}-(ET){sub 2}Cu[N(CN){sub 2}]Cl is a two- dimensionally structured organic material with a rich pressure vs. temperature phase diagram including paramagnetic and antiferromagnetic Mott-insulating states as well as metallic, semiconducting and superconducting phases, see e.g. We used X-ray irradiation to induce defects in the material and by this change the charge distribution between anion- and ET-layers. The smaller resistivity of the irradiated samples compared to non-irradiated ones supports this idea. As a consequence, X-ray irradiation may provide a means for doping the Mott-insulator away from half-filling. We present resistivity data for the temperature range 5 K{<=}T{<=}60 K and pressures up to 50 MPa from which the p-T-phase diagram of X-ray irradiated {kappa}-(ET){sub 2}Cu[N(CN){sub 2}]Cl is extracted.

  4. Confidence intervals for the weighted kappa coefficient of a binary diagnostic test


    Roldán Nofuentes, José Antonio; Luna Del Castillo, Juan De Dios; Montero Alonso, Miguel Angel; Alvarado Castro, Victor Manuel


    Abstract Sensitivity and specificity are classic parameters to assess the performance of a binary diagnostic test. Another useful parameter to measure the performance of a binary test is the weighted kappa coefficient, which is a measure of the classificatory agreement between the binary test and the gold standard. Various confidence intervals are proposed for the weighted kappa coefficient when the binary test and the gold standard are applied to all of the patients in a random sa...

  5. Effects of kappa-opioid receptor ligands on intracranial self-stimulation in rats. (United States)

    Todtenkopf, Mark S; Marcus, Jacqueline F; Portoghese, Philip S; Carlezon, William A


    Elevations in cAMP response element binding protein (CREB) function within the mesolimbic system of rats reduce cocaine reward in place conditioning studies and increase immobility in the forced swim test. Each of these behavioral adaptations can be interpreted as a depressive-like effect (i.e., anhedonia, despair) that may reflect reduced activity of brain reward systems. Furthermore, each effect appears due to increases in CREB-mediated expression of dynorphin, since each is attenuated by intracranial injections of the kappa-opioid receptor antagonist norBNI. Intracranial self-stimulation (ICSS) studies were conducted in rats to determine whether administration of a kappa-agonist would have depressive-like effects on brain stimulation reward, and whether pretreatment with a kappa-antagonist would attenuate any such effects. Conditions that have depressive effects in people (e.g., drug withdrawal) increase the threshold amounts of stimulation required to sustain ICSS in rats. Sprague-Dawley rats with lateral hypothalamic stimulating electrodes were tested in a "curve-shift" variant of the ICSS procedure after systemic administration of the kappa-agonist U-69593 alone, the novel kappa-antagonist 5'-acetamidinoethylnaltrindole (ANTI) alone, or co-administration of both drugs. U-69593 dose dependently increased ICSS thresholds, suggesting that activation of kappa-receptors reduced the rewarding impact of the brain stimulation. ANTI had no effects on its own, but it attenuated increases in ICSS thresholds caused by the agonist. These data provide further evidence that stimulation of brain kappa-receptors may trigger certain depressive-like signs, and that kappa antagonists may have efficacy as antidepressants without having reward-related actions of their own.

  6. Role of nuclear factor-kappaB in interleukin-1-induced collagen degradation by corneal fibroblasts. (United States)

    Lu, Ying; Fukuda, Ken; Li, Qin; Kumagai, Naoki; Nishida, Teruo


    The proinflammatory cytokine interleukin (IL)-1 is implicated in corneal ulceration. The role of nuclear factor (NF)-kappaB in the IL-1-induced degradation of collagen by corneal fibroblasts that underlies corneal ulceration was investigated. Rabbit corneal fibroblasts were cultured in three-dimensional gels of type I collagen with or without IL-1 and sulfasalazine, an inhibitor of NF-kappaB activation. Collagen degradation was assessed from the amount of hydroxyproline generated by acid-heat hydrolysis of culture supernatants. The release of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) into culture supernatants was examined by immunoblot analysis and gelatin zymography, and the cellular abundance of MMP and TIMP mRNAs was determined by reverse transcription and real-time polymerase chain reaction analysis. The phosphorylation and degradation of the NF-kappaB-inhibitory protein IkappaB-alpha were examined by immunoblot analysis. The subcellular localization and DNA binding activity of the p65 subunit of NF-kappaB were evaluated by immunofluorescence analysis and with a colorimetric assay, respectively. The transactivation activity of NF-kappaB was assessed with a reporter gene assay. Sulfasalazine inhibited IL-1-induced collagen degradation by corneal fibroblasts in a concentration-dependent manner. It also inhibited the stimulatory effects of IL-1 on the synthesis or activation of various MMPs in a concentration-dependent manner. IL-1 induced the phosphorylation and degradation of IkappaB-alpha, the nuclear translocation and up-regulation of the DNA binding activity of the p65 subunit of NF-kappaB, and the activation of NF-kappaB in a manner sensitive to sulfasalazine. These results suggest that NF-kappaB contributes to the IL-1-induced degradation of collagen by corneal fibroblasts and is therefore a potential therapeutic target for treatment of corneal ulcers.

  7. Differential rotation of the active G5V star Kappa1 Ceti: Photometry from the MOST satellite

    CERN Document Server

    Rucinski, S M; Matthews, J M; Kuschnig, R; Shkolnik, E; Marchenko, S; Bohlender, D A; Günther, D B; Moffat, A F J; Sasselov, D; Weiss, W W; Rucinski, Slavek M.; Walker, Gordon A.H.; Matthews, Jaymie M.; Kuschnig, Rainer; Shkolnik, Evgenya; Marchenko, Sergey; Bohlender, David A.; Moffat, Anthony F.J.; Sasselov, Dimitar; Weiss, Werner W.


    About 30.5 days of nearly uninterrupted broadband photometry of the solar-type star Kappa1 Ceti, obtained with the MOST (Microvariability & Oscillations of STars) satellite, shows evidence for two large starspots with different rotation periods of 8.9 and approximately 9.3 days (DeltaOmega/Omega~4%). Ground based measurements in 2002 and 2003 of Ca II H & K emission reveal variations in chromospheric activity with a period of about 9.3 days. The data were obtained during the MOST commissioning phase. When the data are combined with historical observations, they indicate that the 9.3-day spot has been stable in its period for over 30 years. The photometry, with a sampling rate of approximately once per minute, was also used to search for acoustic (p-mode) oscillations in the star. We detect no clear evidence for p-modes in the Kappa1 Ceti photometry, with a noise level around 7-9 mu_mag at frequencies in the range 0.5-4 mHz (3-sigma detection limit of 21 - 27 mu_mag). There were no flares or planetary ...

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

    Energy Technology Data Exchange (ETDEWEB)

    Lagirand-Cantaloube, Julie, E-mail: [UMR8113 CNRS, LBPA, Ecole Normale Superieure, Cachan (France); Laud, Karine, E-mail: [U830 INSERM, Institut Curie, Paris (France); Institut Curie, Genetique et biologie des cancers, Paris (France); Lilienbaum, Alain, E-mail: [EA300 Universite Paris 7, Stress et pathologies du cytosquelette, Paris (France); Tirode, Franck, E-mail: [U830 INSERM, Institut Curie, Paris (France); Institut Curie, Genetique et biologie des cancers, Paris (France); Delattre, Olivier, E-mail: [U830 INSERM, Institut Curie, Paris (France); Institut Curie, Genetique et biologie des cancers, Paris (France); Auclair, Christian, E-mail: [UMR8113 CNRS, LBPA, Ecole Normale Superieure, Cachan (France); Kryszke, Marie-Helene, E-mail: [UMR8113 CNRS, LBPA, Ecole Normale Superieure, Cachan (France)


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

  9. The role of the dynorphin-kappa opioid system in the reinforcing effects of drugs of abuse. (United States)

    Wee, Sunmee; Koob, George F


    Initial hypotheses regarding the role of the kappa opioid system in drug addiction suggested that kappa receptor stimulation had anti-addictive effects. However, recent research suggests that kappa receptor antagonists may reverse motivational aspects of dependence. In the present review, we revisit the studies that measured the effects of kappa receptor ligands on the reinforcing and rewarding effects of drugs and postulate underlying neurobiological mechanisms for these effects to elaborate a more complex view of the role of kappa receptor ligands in drug addiction. The review of studies indicates that kappa receptor stimulation generally antagonizes the acute reinforcing/rewarding effects of drugs whereas kappa receptor blockade has no consistent effect. However, in a drug dependent-like state, kappa receptor blockade was effective in reducing increased drug intake. In animal models of reinstatement, kappa receptor stimulation can induce reinstatement via a stress-like mechanism. Results in conditioned place preference/aversion and intracranial self-stimulation indicate that kappa receptor agonists produce, respectively, aversive-like and dysphoric-like effects. Additionally, preclinical and postmortem studies show that administration or self-administration of cocaine, ethanol, and heroin activate the kappa opioid system. kappa receptor agonists antagonize the reinforcing/rewarding effects of drugs possibly through punishing/aversive-like effects and reinstate drug seeking through stress-like effects. Evidence suggests that abused drugs activate the kappa opioid system, which may play a key role in motivational aspects of dependence. Kappa opioid systems may have an important role in driving compulsive drug intake.

  10. Role of nuclear factor kappa B in central nervous system regeneration

    Institute of Scientific and Technical Information of China (English)

    Christian Engelmann; Falk Weih; Ronny Haenold


    Activation of nuclear factor kappa B (NF-κB) is a hallmark of various central nervous system (CNS) pathologies. Neuron-speciifc inhibition of its transcriptional activator subunit RelA, also referred to as p65, promotes neuronal survival under a range of conditions, i.e., for ischemic or excitotoxic insults. In macro-and microglial cells, post-lesional activation of NF-κB triggers a growth-permissive program which contributes to neural tissue inlfammation, scar formation, and the expression of axonal growth inhibitors. Intriguingly, inhibition of such inducible NF-κB in the neuro-glial compartment, i.e., by genetic ablation of RelA or overexpression of a trans-dominant negative mutant of its upstream regulator IκBα, significantly enhances functional recovery and promotes axonal regeneration in the mature CNS. By contrast, depletion of the NF-κB subunit p50, which lacks transcriptional activator function and acts as a transcriptional repressor on its own, causes precocious neuronal loss and exacerbates axonal degeneration in the lesioned brain. Collectively, the data imply that NF-κB orchestrates a multicellular pro-gram in whichκB-dependent gene expression establishes a growth-repulsive terrain within the post-lesioned brain that limits structural regeneration of neuronal circuits. Considering these subunit-speciifc functions, interference with the NF-κB pathway might hold clinical potentials to improve functional restoration following traumatic CNS injury.

  11. Misestimation of temperature when applying Maxwellian distributions to space plasmas described by kappa distributions (United States)

    Nicolaou, Georgios; Livadiotis, George


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

  12. HIV gp120 induces, NF-kappaB dependent, HIV replication that requires procaspase 8.

    Directory of Open Access Journals (Sweden)

    Gary D Bren

    Full Text Available BACKGROUND: HIV envelope glycoprotein gp120 causes cellular activation resulting in anergy, apoptosis, proinflammatory cytokine production, and through an unknown mechanism, enhanced HIV replication. METHODOLOGY/PRINCIPAL FINDINGS: We describe that the signals which promote apoptosis are also responsible for the enhanced HIV replication. Specifically, we demonstrate that the caspase 8 cleavage fragment Caspase8p43, activates p50/p65 Nuclear Factor kappaB (NF-kappaB, in a manner which is inhibited by dominant negative IkappaBalpha. This caspase 8 dependent NF-kappaB activation occurs following stimulation with gp120, TNF, or CD3/CD28 crosslinking, but these treatments do not activate NF-kappaB in cells deficient in caspase 8. The Casp8p43 cleavage fragment also transactivates the HIV LTR through NF-kappaB, and the absence of caspase 8 following HIV infection greatly inhibits HIV replication. CONCLUSION/SIGNIFICANCE: Gp120 induced caspase 8 dependent NF-kappaB activation is a novel pathway of HIV replication which increases understanding of the biology of T-cell death, as well as having implications for understanding treatment and prevention of HIV infection.

  13. Shuanghuanglian injection downregulates nuclear factor-kappa B expression in mice with viral encephalitis

    Institute of Scientific and Technical Information of China (English)

    Naibing Gu; Ye Tian; Zhengli Di; Caiping Han; Hui Lei; Gejuan Zhang


    A mouse model of viral encephalitis was induced by intracranial injection of a Coxsackie virus B3 suspension.Quantitative real-time reverse transcription-PCR and western blot assay were applied to detect mRNA and protein expression of intelectin-2 and nuclear factor-kappa B in the viral encephalitis and control groups.Nuclear factor-kappa B and intelectin-2 mRNA and protein expression were significantly increased in mice with viral encephalitis.After intraperitoneal injection of Shuanghuanglian at a dose of 1.5 mg/kg for 5 successive days,intelectin-2 and nuclear factor-kappa B protein and mRNA expression were significantly decreased.To elucidate the relationship between intelectin-2 and nuclear factor-kappa B,mice with viral encephalitis were administered an intracerebral injection of 107 pfu recombinant lentivirus expressing intelectin shRNA.Both protein and mRNA levels of intelectin and nuclear factor-kappa B in brain tissue of mice were significantly decreased.Experimental findings suggest that Shuanghuanglian injection may downregulate nuclear factor-kappa B production via suppression of intelectin production,thus inhibiting inflammation associated with viral encephalitis.

  14. Genetics vs. entropy: longevity factors suppress the NF-kappaB-driven entropic aging process. (United States)

    Salminen, Antero; Kaarniranta, Kai


    Molecular studies in model organisms have identified potent longevity genes which can delay the aging process and extend the lifespan. Longevity factors promote stress resistance and cellular survival. It seems that the aging process itself is not genetically programmed but a random process involving the loss of molecular fidelity and subsequent accumulation of waste products. This age-related increase in cellular entropy is compatible with the disposable soma theory of aging. A large array of host defence systems has been linked to the NF-kappaB system which is an ancient signaling pathway specialized to host defence, e.g. functioning in immune system. Emerging evidence demonstrates that the NF-kappaB system is activated during aging. Oxidative stress and DNA damage increase with aging and elicit a sustained activation of the NF-kappaB system which has negative consequences, e.g. chronic inflammatory response, increase in apoptotic resistance, decline in autophagic cleansing, and tissue atrophy, i.e. processes that enhance the aging process. We will discuss the role of NF-kappaB system in the pro-aging signaling and will emphasize that several longevity factors seem to be inhibitors of NF-kappaB signaling and in that way they can suppress the NF-kappaB-driven entropic host defence catastrophe.

  15. The dynamic relationship between mu and kappa opioid receptors in body temperature regulation. (United States)

    Chen, Xiaohong; McClatchy, Daniel B; Geller, Ellen B; Tallarida, Ronald J; Adler, Martin W


    Previous studies demonstrated that intracerebroventricular (icv) injection of a kappa opioid receptor agonist decreased, and a mu agonist increased, body temperature (Tb) in rats. A dose-response study with the selective kappa antagonist nor-binaltorphimine (nor-BNI) showed that a low dose (1.25 nmol, icv) alone had no effect, although a high dose (25 nmol, icv) increased Tb. It was hypothesized that the hyperthermia induced by nor-BNI was the result of the antagonist blocking the kappa opioid receptor and releasing its inhibition of mu opioid receptor activity. To determine whether the Tb increase caused by nor-BNI was a mu receptor-mediated effect, we administered the selective mu antagonist CTAP (1.25 nmol, icv) 15 min after nor-BNI (25 nmol, icv) and measured rectal Tb in unrestrained rats. CTAP significantly antagonized the Tb increase induced by icv injection of nor-BNI. Injection of 5 or 10 nmol of CTAP alone significantly decreased the Tb, and 1.25 nmol of nor-BNI blocked that effect, indicating that the CTAP-induced hypothermia was kappa-mediated. The findings strongly suggest that mu antagonists, in blocking the basal hyperthermia mediated by mu receptors, can unmask the endogenous kappa receptor-mediated hypothermia, and that there is a tonic balance between mu and kappa opioid receptors that serves as a homeostatic mechanism for maintaining Tb.

  16. 7-Ketocholesterol Induces Cell Apoptosis by Activation of Nuclear Factor kappa B in Mouse Macrophages

    Directory of Open Access Journals (Sweden)



    Full Text Available

    We investigated the molecular mechanisms responsible for the induction of apoptosis in mouse monocytic macrophage cell line J774A.1 stimulated by 7-ketocholesterol (7-KC. Cell apoptosis was detected by Annexin V-propidium iodide (PI staining. The DNA-binding activity of nuclear factor kappa B (NF-kappaB was assessed by electrophoretic mobility shift assay (EMSA. Results showed that 7-KC-stimulation in J774A.1 cells activated NF-kappaB, which is involved in cell apoptosis, in a time- and dose-dependent manners. 7-KC was also found to increase the binding activity of NF-kappaB to specific DNA binding sites, a possible mechanism for the induction of the cell apoptosis. Moreover, these effects were partially inhibited by pyrrolidine dithiocarbamate (PDTC, an NF-kappaB inhibitor. Taken together, 7-KC may be an important factor in atherosclerosis due to the ability of 7-KC to induce cell apoptosis, which is at least partially mediated through the activation of NF-kappaB.

  17. Hemorrhage activates NF-kappa B in murine lung mononuclear cells in vivo. (United States)

    Shenkar, R; Schwartz, M D; Terada, L S; Repine, J E; McCord, J; Abraham, E


    Hemorrhage rapidly increases the expression of proinflammatory and immunoregulatory cytokines in the lungs. Binding elements for the nuclear transcriptional regulatory factors (NF)-kappa B and NF-IL6 (C/EBP beta) are present in the promoter regions of multiple cytokine genes, including those whose expression is increased after blood loss. In the present experiments, we found increased activation in vivo of NF-kappa B in lung mononuclear cells, but not in splenocytes, taken from mice 1 h after hemorrhage. In contrast, hemorrhage did not activate NF-IL6 in lung cells or splenocytes. Inhibition of xanthine oxidase by prior feeding of a tungsten-enriched diet prevented hemorrhage-induced activation in lung cells of NF-kappa B. Incubating splenocytes in vitro with xanthine oxidase activated NF-kappa B but not NF-IL6. Xanthine oxidase-induced activation of NF-kappa B was inhibited by manganese superoxide dismutase, but not by catalase. These results suggest that xanthine oxidase-mediated superoxide anion-dependent activation of NF-kappa B occurs in vivo and in vitro. This mechanism may contribute to increased lung cytokine responses after hemorrhage.

  18. CARMA1 is required for Akt-mediated NF-kappaB activation in T cells. (United States)

    Narayan, Preeti; Holt, Brittany; Tosti, Richard; Kane, Lawrence P


    Many details of the generic pathway for induction of NF-kappaB have been delineated, but it is still not clear how multiple, diverse receptor systems are able to converge on this evolutionarily conserved family of transcription factors. Recent studies have shown that the CARMA1, Bcl10, and MALT1 proteins are critical for coupling the common elements of the NF-kappaB pathway to the T-cell receptor (TCR) and CD28. We previously demonstrated a role for the serine/threonine kinase Akt in CD28-mediated NF-kappaB induction. Using a CARMA1-deficient T-cell line, we have now found that the CARMA complex is required for induction of NF-kappaB by Akt, in cooperation with protein kinase C activation. Furthermore, using a novel selective inhibitor of Akt, we confirm that Akt plays a modulatory role in NF-kappaB induction by the TCR and CD28. Finally, we provide evidence for a physical and functional interaction between Akt and CARMA and for Akt-dependent phosphorylation of Bcl10. Therefore, in T cells, Akt impinges upon NF-kappaB signaling through at least two separate mechanisms.

  19. NF-kappaB function in the human myometrium during pregnancy and parturition. (United States)

    Cookson, Victoria J; Chapman, Neil R


    Interactions between the nuclear factor kappaB (NF-kappaB) family of proteins (RelA, RelB, c-Rel, p50 and p52) and DNA are vital for cells to function normally; for example, in the human myometrium, NF-kappaB-regulated pro-inflammatory mediators, including TNFalpha, IL-1beta, IL-8 and COX-2 are associated with the onset of labour. NF-kappaB, however, regulates the expression of over 400 genes, although it is unlikely these would all be activated in concert by a single inducer. At present, defining the role of the NF-kappaB RelA:p50 dimer, which governs a number of inflammatory promoters, is at the forefront of the parturition research field. However, to over-look the function of other family members and how they may regulate alternative signalling networks within reproductive tissues, only serves to ensure we will never fully understand the molecular circuitry influenced by this family of transcription factors. Consequently this review highlights other mechanisms by which the NF-kappaB family of regulators have been shown to function in other systems and how they may readily translate to understanding the regulation underpinning human parturition.

  20. Stereoselective synthesis and structure-affinity relationships of bicyclic kappa receptor agonists. (United States)

    Kracht, Daniel; Rack, Elisabeth; Schepmann, Dirk; Fröhlich, Roland; Wünsch, Bernhard


    Reductive amination of the bicyclic ketone 4 led diastereoselectively to endo-configured amines, which were transformed into the amides 7-10. The synthesis of the diastereomers 25 with an exo-configured amino moiety at position 6 was only successful after deactivation of both N-atoms of the 1,4-diazabicyclo[3.3.1]nonane system. The N-1-oxide 19 with an N-4-tosyl moiety was the crucial intermediate, which allows SN2 substitution with NaN3 under inversion of the configuration at position 6. Whereas the endo-configured pyrrolidine 7a (WMS-1302) revealed a kappa receptor affinity of 73 nM, the exo-configured diastereomer 25a was almost inactive at the kappa receptor (Ki > 1 microM). Replacement of the 3,4-dichlorophenylacetyl residue by other acyl and sulfonyl residues showed that it is essential for high kappa affinity. The kappa receptor affinities of the conformationally constrained pyrrolidines 7a and 25a were correlated with the dihedral angle N(pyrrolidine)-C-C-N(acetamide). A systematic conformational analysis of the potent but flexible kappa agonist 2 showed that a dihedral angle of 168 degrees (as in 25a) is energetically more disfavored than a dihedral angle of 58 degrees (7a). However, even the conformation with a dihedral angle of 58 degrees does not represent an energy minimum, which might explain the reduced kappa affinity of 7a.

  1. Relative locality in a quantum spacetime and the pregeometry of {kappa}-Minkowski

    Energy Technology Data Exchange (ETDEWEB)

    Amelino-Camelia, Giovanni; Astuti, Valerio [Universita di Roma ' ' La Sapienza' ' , Dipartimento di Fisica, Roma (Italy); Sez. Roma1, INFN, Roma (Italy); Rosati, Giacomo [Universita di Roma ' ' La Sapienza' ' , Dipartimento di Fisica, Roma (Italy); Sez. Roma1, INFN, Roma (Italy); University of Wroclaw, Institute for Theoretical Physics, Wroclaw (Poland)


    We develop a description of the much-studied {kappa}-Minkowski noncommutative spacetime, centered on representing on a single Hilbert space not only the {kappa}-Minkowski coordinates, but also the {kappa}-Poincare symmetry generators and some suitable relativistic-transformation parameters. In this representation the relevant operators act on the kinematical Hilbert space of the covariant formulation of quantum mechanics, which we argue is the natural framework for studying the implications of the step from commuting spacetime coordinates to the {kappa}-Minkowski case, where the spatial coordinates do not commute with the time coordinate. Within this kinematical-Hilbert-space representation we can give a crisp characterization of the ''fuzziness'' of points in {kappa}-Minkowski spacetime, also allowing us to describe how the same fuzzy point is seen by different relativistic observers. The most striking finding of our analysis is a relativity of spacetime locality in {kappa}-Minkowski. While previous descriptions of relative locality had been formulated exclusively in classical-spacetime setups, our analysis shows how relative locality in a quantum spacetime takes the shape of a dependence of the fuzziness of a spacetime point on the distance at which an observer infers properties of the event that marks the point. (orig.)

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

    Energy Technology Data Exchange (ETDEWEB)

    Richard R. Gustafson; James B. Callis


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

  3. Prognostic value of serum free light chain ratio at diagnosis in multiple myeloma. (United States)

    Kyrtsonis, Marie-Christine; Vassilakopoulos, Theodoros P; Kafasi, Nicoletta; Sachanas, Sotirios; Tzenou, Tatiana; Papadogiannis, Argiroula; Galanis, Zacharoula; Kalpadakis, Christina; Dimou, Maria; Kyriakou, Elias; Angelopoulou, Maria K; Dimopoulou, Maria N; Siakantaris, Marina P; Dimitriadou, Evangelia M; Kokoris, Styliani I; Panayiotidis, Panayiotis; Pangalis, Gerassimos A


    The prognostic value of baseline serum free light chain ratio (sFLCR) was investigated in 94 multiple myeloma (MM) patients. sFLCR was calculated as kappa/lambda or lambda/kappa, depending on the patients' dominating monoclonal light chain. Median baseline sFLCR was 3.57 in kappa-MM patients, 45.09 in lambda-MM. 'High' sFLCR (> or = the observed median value for kappa- and lambda-MM respectively) correlated with elevated serum creatinine and lactate dehydrogenase, extensive marrow infiltration and light chain type MM. The 5-year disease-specific survival was 82% and 30% in patients with sFLCR lower than and equal or greater than the median, respectively (P = 0.0001). sFLCR was an independent prognostic factor.

  4. The new kappa-KTx 2.5 from the scorpion Opisthacanthus cayaporum. (United States)

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


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

  5. Radial shock waves effectively introduced NF-kappa B decoy into rat achilles tendon cells in vitro. (United States)

    Sugioka, Kaori; Nakagawa, Koichi; Murata, Ryo; Ochiai, Nobuyasu; Sasho, Takahisa; Arai, Momoko; Tsuruoka, Hiroaki; Ohtori, Seiji; Saisu, Takashi; Gemba, Takefumi; Takahashi, Kazuhisa


    The purpose of this study was to test if radial shock waves could enhance the introduction of nuclear factor-kappa B (NF-kappaB) decoy oligodeoxynucleotides, which is reported to markedly inhibit NF-kappaB activation and suppress pro-inflammatory cytokine gene expression, using rat Achilles tendon cells. In the presence of NF-kappaB decoy labeled with or without fluorescein isothiocyanate (FITC) in culture media, radial shock waves were applied to the tendon cells in variable conditions and cultivated for 24 h. The transfection rate was assessed by counting FITC-positive cells, and IL-1-induced NF-kappaB activation in the cells was assessed. Radial shock waves significantly enhanced introduction of NF-kappaB decoy-FITC into the tendon cells. IL-1-induced NF-kappaB activation was significantly inhibited by pretreatment of the cells with NF-kappaB decoy combined with radial shock wave exposure. The present study demonstrated the effectiveness of radial shock waves on introduction of NF-kappaB decoy into tendon cells. Radial shock wave treatment combined with local NF-kappaB decoy administration could be a novel therapeutic strategy for chronic tendinopathy.

  6. Range Information Propagation Transform

    Institute of Scientific and Technical Information of China (English)

    陈向荣; 朱志刚; 等


    A novel method of model-based object recognition is presented in this paper.Its novelty stems from the fact that the gray level image captured by a camera is merged with sparse range information in an active manner.By using a projective transform, which is determined by the sparse range data,festures(e.g.edge points)related to a single planar surface patch of figure in the scene can be assignew with their corresponding range values respectively.As a result,the shape of the very planar patch or figure can be recovered and various kinds of description in the Euclidean space can be calculated.Based on these descriptions values,the hypothesis about the identification of the object and its pose in space can be obtained with a high probability of success,and a high efficiency of hypothesis-verification process can be expected.Another advantage of this method is that the edge detection process can be navigated to the proper location hinted by the sparse range image.In consequence edge features can be extracted even in the regions with low contrast.In this paper the principle of range information propagation transform(RIPT)is explained,and some implementation issues,such as the algorithms using calibrated or uncalibrated gray level image for object recognition,are discussed.The preliminary experimental results are presented to indicate the effectiveness and efficiency of the proposed method.

  7. Uncaria tomentosa acts as a potent TNF-alpha inhibitor through NF-kappaB. (United States)

    Allen-Hall, Lisa; Arnason, John T; Cano, Pablo; Lafrenie, Robert M


    Uncaria tomentosa, commonly known as Cat's Claw or Uña de gato, is a medicinal plant that has been shown to have effective anti-inflammatory activities. We have previously shown that treatment of monocyte-like THP-1 cells with Uncaria tomentosa inhibits the production of the pro-inflammatory cytokine TNF-alpha while augmenting the production of IL-1beta. Since TNF-alpha and IL-1beta are usually regulated similarly and share a number of common promoter elements, including NF-kappaB and AP-1, the ability of Uncaria tomentosa to differentially regulate these inflammatory cytokines is of particular interest. To determine the mechanism of action of Uncaria tomentosa, we investigated the effects of specific inhibitors of NF-kappaB on cellular responses including transcription factor activation using TransAM assays, the expression of cytokines as measured by ELISA, and cell survival as measured by changes in cell number following treatment. Treatment with Uncaria tomentosa inhibited the LPS-dependent activation of specific NF-kappaB and AP-1 components. In addition, treatment with Uncaria tomentosa enhanced cell death when NF-kappaB was inhibited. The ability of Uncaria tomentosa to inhibit TNF-alpha production was diminished when NF-kappaB activation was prevented by drugs that mask NF-kappaB subunit nuclear localization signals, while IL-1beta expression was unchanged. These results demonstrate that Uncaria tomentosa is able to elicit a response via an NF-kappaB-dependent mechanism. Further studies to characterize the mechanism by which Uncaria tomentosa can affect this pathway could provide a means to develop anti-TNF-alpha therapies. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  8. Significant differences in physicochemical properties of human immunoglobulin kappa and lambda CDR3 regions

    Directory of Open Access Journals (Sweden)

    Catherine L Townsend


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

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

    Directory of Open Access Journals (Sweden)

    Emiliano Merlo

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

  10. Significant Differences in Physicochemical Properties of Human Immunoglobulin Kappa and Lambda CDR3 Regions. (United States)

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


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

  11. Andrographolide inhibits NF-kappaBeta activation and attenuates neointimal hyperplasia in arterial restenosis. (United States)

    Wang, Yu-Jiu; Wang, Jin-Tao; Fan, Quan-Xin; Geng, Jian-Guo


    The NF-kappaBeta transcription factors modulate the expression of tissue factor (TF), E-selectin (CD62E) and vascular cell adhesion molecule-1 (VCAM-1), which are essential for thrombosis and inflammation. We have previously shown that andrographolide (Andro) covalently modifies the reduced cysteine(62) of p50 - a major subunit of NF-kappaBeta transcription factors, thus blocking the binding of NF-kappaBeta transcription factors to the promoters of their target genes, preventing NF-kappaBeta activation and inhibiting inflammation in vitro and in vivo. Here we report that Andro, but not its inactive structural analog 4H-Andro, significantly suppressed the proliferation of arterial neointima ( approximately 60% reduction) in a murine model of arterial restenosis. Consistently, p50(-/-) mice manifested attenuated neointimal hyperplasia upon arterial ligation. Notably, the same dosage of Andro did not further reduce neointimal formation in p50(-/-) mice, which implicates the specificity of Andro on p50 for treating experimental arterial restenosis. The upregulation of NF-kappaBeta target genes, including TF, E-selectin and VCAM-1, and the increased deposition of leukocytes (mainly CD68+ macrophages) were clearly detected within the injured arterial walls, all of which were significantly abolished by treatment with Andro or genetic deletion of p50. The expression of TF, E-selectin and VCAM-1 was also markedly upregulated in the patient sample of thrombotic vasculitis, indicating the clinical relevance of NF-kappaBeta activation in the pathogeneses of occlusive arterial diseases. Our data thus indicate that, by the downregulation of the NF-kappaBeta target genes that are critical in thrombosis and inflammation, specific inhibitors of p50, such as Andro, may be therapeutically valuable for preventing and treating thrombotic arterial diseases, including neointimal hyperplasia in arterial restenosis.

  12. Caseinomacropeptide self-association is dependent on whether the peptide is free or restricted in kappa-casein

    DEFF Research Database (Denmark)

    Mikkelsen, T.L.; Frokiaer, H.; Topp, C.


    There is a general agreement that the experimentally determined molecular weight (MW) of caseinomacropeptide (CMP) is greater than the theoretical MW. Some studies suggest that this is due to a pH-dependent aggregation of monomeric CMP. How this aggregation is influenced by pH is not understood....... This study was carried out to study the nature of CMP aggregates and to clarify which conditions affect aggregation of CMP. The apparent MW of CMP at different pH values was determined using size-exclusion chromatography. Caseinomacropeptide was further characterized by immunochemical analysis, sodium...... dodecyl sulfate-PAGE, N-terminal sequencing, and mass spectrometry. The hydrophobicity of CMP was studied by means of 1-anilino-naphthalene-8-sulfonic acid binding experiments. Four CMP products prepared by different methods were studied: CMP produced by enzymatic (chymosin or pepsin) hydrolysis of kappa...

  13. Hemostatic efficacy evaluation of radiation crosslinked carboxymethyl kappa-carrageenan and chitosan with varying degrees of substitution (United States)

    Tranquilan-Aranilla, Charito; Barba, Bin Jeremiah D.; Vista, Jeanina Richelle M.; Abad, Lucille V.


    Carboxymethyl derivatives of kappa-carrageenan and chitosan, with varying degrees of substitution, were synthesized by multi-step reaction technique and evaluated for hemostatic efficacy through in vitro assays. FTIR analysis confirmed the presence of carboxymethyl group while 1H NMR spectroscopy indicated degrees of substitution ranging from 1.15-1.58 and 0.45-0.51 for carboxymethyl-κ-carrageenan and carboxymethylchitosan, respectively. Derivatives formed into paste consistency (30% w/v) were successfully crosslinked by gamma irradiation at 30 kGy. The data obtained from whole blood clotting and platelet adhesion assays showed a significant increase in hemostatic capability of κ-carrageenan and chitosan as a consequence of carboxymethylation and crosslinking modifications. In addition, the level of efficacy was comparable to that of a chitosan-based commercial product. These results suggest the potential of κ-carrageenan and chitosan derivatives for development into hemostatic agents.

  14. Effect of kappa elastin on melanogenesis in A375 human melanoma cells and its related mechanism

    Institute of Scientific and Technical Information of China (English)

    TIAN Shan; HE Pei-ying; ZHANG Jian-zhong; CHEN Zhou


    Background Elastin derived peptides can regulate melanocyte precursor development.Ultraviolet irradiation,infrared radiation and heat can increase the synthesis of tropoelastin in human skin epidermis.The aim of this study was to investigate whether the over expressed tropoelastin in epidermis has some role in melanogenesis of melanocytes.Methods A375 human melanoma cells were treated with different concentrations of kappa elastin for 24 hours.A375 human melanoma cells were randomly assigned to control,kappa elastin,and lactose pre-incubated groups.The cell viabilities were detected by the methyl thiazoleterazolium assay.Melanin content and tyrosinase activity in A375 melanoma cells were measured.The expressions of endothelin B receptor(ETBR)mRNA and c-kit mRNA in A375 melanoma cells were measured by quantative reverse transcription polymerase chain reaction.Results Fifty μg/ml of kappa elastin significantly increased the melanin content by 56.64% compared with the control(P<0.05).Kappa elastin increased cellular tyrosinase activity by 46.73% compared with the control at 24 hours(P<0.05).Kappa elastin increased the expressions of ETBR and c-kit mRNA levels by 2.13-fold and 2.47-fold compared with the controls,respectively.When pre-incubating cells with a lactose solution(10 mmol/L),the inhibition on melanin production was 34.96% compared with the kappa elastin group(P<0.05),tyrosinase activity was inhibited by 29.93% compared with kappa elastin group(P<0.05),and the expressions of ETBR mRNA and c-kit mRNA were decreased by 1.56-fold and 0.82-fold compared with kappa elastin group,respectively.Conclusion Kappa elastin increased the melanogenesis in A375 melanoma cells via the stimulation of tyrosinase activity and the expression of ETBR and c-kit.The over expressed tropoelastin produced by keratinocytes might play a role in melanogenesis of epidermal melanocytes.

  15. Water soluble graft copolymer ({kappa}-carrageenan-g-N-vinyl formamide): preparation, characterization and application

    Energy Technology Data Exchange (ETDEWEB)

    Mishra, M.M.; Yadav, M.; Sand, A.; Tripathy, J.; Behari, K. [University of Allahabad, Allahabad (India). Dept. of Chemistry


    {kappa}-Carrageenan-g-N-vinyl formamide was synthesized by free radical initiation using the potassium monopersulphate (PMS)/malonic acid redox pair in an inert atmosphere. The effects of variation of different reactant oil grafting parameters have been studied by varying the concentration. Grafting ratio, add on and conversion showed an increasing trend on increasing the concentration of N-vinyl formamide, malonic acid, kappa-carrageenart and the concentration of PMS from 6 x 10{sup -3} to 22 x 10{sup -3} mol dm{sup -3}. The optimum temperature and time for grafting of N-vinyl formamide onto {kappa}-carrageenan was found to be 40{sup o}C and 120 min, respectively. The metal ion sorption, swelling behaviour, flocculation and resistance to biodegradation properties have been studied. Flocculation capability of {kappa}-carrageenart and {kappa}-carrageenan-g-N-vinyl formamide for both coking and non-coking coals has been studied for the treatment of coal mine waste water. The graft copolymer was characterized by FT-IR spectroscopy and thermogravimetric analysis.

  16. Interactions between CBP, NF-kappaB, and CREB in the lungs after hemorrhage and endotoxemia. (United States)

    Shenkar, R; Yum, H K; Arcaroli, J; Kupfner, J; Abraham, E


    The transcriptional regulatory factor nuclear factor (NF)-kappaB has a central role in modulating expression of proinflammatory mediators that are important in acute lung injury. In vitro studies have shown that competition between NF-kappaB and cAMP response element binding protein (CREB) for binding to the coactivator CREB-binding protein (CBP) is important in regulating transcriptional activity of these factors. In the present study, we examined in vivo interactions between CBP, CREB, and NF-kappaB in hemorrhage- or endotoxemia-induced acute lung injury. Association of CBP with CREB or the p65 subunit of NF-kappaB increased in the lungs after hemorrhage or endotoxemia. Inhibition of xanthine oxidase before hemorrhage, but not before endotoxemia, decreased p65-CBP interactions while increasing those between CREB and CBP. These alterations in CREB-CBP and p65-CBP interactions were functionally significant because xanthine oxidase inhibition before hemorrhage resulted in increased expression of the CREB-dependent gene c-Fos and decreased expression of macrophage inflammatory protein-2, a NF-kappaB-dependent gene. The present results show that the coactivator CBP has an important role in modulating transcription in vivo under clinically relevant pathophysiological conditions.

  17. DMPD: Signaling to NF-kappaB by Toll-like receptors. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18029230 Signaling to NF-kappaB by Toll-like receptors. Kawai T, Akira S. Trends Mo...l Med. 2007 Nov;13(11):460-9. Epub 2007 Oct 29. (.png) (.svg) (.html) (.csml) Show Signaling to NF-kappaB by... Toll-like receptors. PubmedID 18029230 Title Signaling to NF-kappaB by Toll-like receptors. Authors Kawai T

  18. Real-time monitoring of nuclear factor kappaB activity in cultured cells and in animal models. (United States)

    Badr, Christian E; Niers, Johanna M; Tjon-Kon-Fat, Lee-Ann; Noske, David P; Wurdinger, Thomas; Tannous, Bakhos A


    Nuclear factor kappaB (NF-kappaB) is a transcription factor that plays a major role in many human disorders, including immune diseases and cancer. We designed a reporter system based on NF-kappaB responsive promoter elements driving expression of the secreted Gaussia princeps luciferase (Gluc). We show that this bioluminescent reporter is a highly sensitive tool for noninvasive monitoring of the kinetics of NF-kappaB activation and inhibition over time, both in conditioned medium of cultured cells and in the blood and urine of animals. NF-kappaB activation was successfully monitored in real time in endothelial cells in response to tumor angiogenic signaling, as well as in monocytes in response to inflammation. Further, we demonstrated dual blood monitoring of both NF-kappaB activation during tumor development as correlated to tumor formation using the NF-kappaB Gluc reporter, as well as the secreted alkaline phosphatase reporter. This NF-kappaB reporter system provides a powerful tool for monitoring NF-kappaB activity in real time in vitro and in vivo.

  19. Judging disease activity in rheumatoid arthritis by serum free kappa and lambda light chain levels. (United States)

    Ye, Yun; Li, Su-Liang; Xie, Ming; Jiang, Ping; Liu, Kai-Ge; Li, Ya-Jun


    The study aimed to evaluate the levels of serum free kappa (κ) and lambda (λ) light chains in patients with rheumatoid arthritis (RA) as well as exploring the association between serum free κ and λ light chains and activity of RA. For this purpose, healthy individuals and patients with active RA and RA in remission were enrolled, and their serum levels of free κ and λ light chains were measured using rate nephelometry. The diagnostic accuracy of serum free κ and λ light chains was evaluated by receiver operating characteristic curves and 95% confidence intervals for areas under the curve (AUC). The results obtained indicated that the levels of serum free κ and λ light chains in patients with active RA were significantly higher than those of patients in remission and of healthy controls (p light chain and 0.781 for free λ light chain. When the optimal cut-off point for serum κ light chain was 8.02 g/L, the maximum sensitivity and specificity were 82.5% and 82.5%, respectively, and when the optimal cut-off point for serum λ light chain was 3.57 g/L, the maximum sensitivity and specificity were 80% and 82.5%, respectively. It was thus found that serum levels of free κ and λ light chains were positively correlated with disease activity in RA, the Disease Activity Score 28 (DAS28), and values for C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), platelet count (PLT), rheumatoid factor (RF), and anticitrullinated protein antibody (ACPA) (p light chains in patients with active RA are closely correlated with disease activity parameters including DAS28, CRP, ESR, PLT, RF, and ACPA. Thus, the above-mentioned levels of serum free κ and λ light chains may be used as important indicators of activity of RA.

  20. Proinflammatory effects of pancreatic elastase are mediated through TLR4 and NF-kappaB. (United States)

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


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

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

    Energy Technology Data Exchange (ETDEWEB)

    Eliasson, B., E-mail: [SUPA, Physics Department, John Anderson Building, Strathclyde University, Glasgow G4 0NG, Scotland (United Kingdom); Lazar, M., E-mail: [Centre for Mathematical Plasma Astrophysics, Celestijnenlaan 200B, 3001 Leuven (Belgium); Institut für Theoretische Physik, Lehrstuhl IV: Weltraum- und Astrophysik, Ruhr-Universität Bochum, 44780 Bochum (Germany)


    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.

  2. Scalar field theory on kappa-Minkowski spacetime and Lorentz covariance

    CERN Document Server

    Meljanac, Stjepan


    We investigate the properties of kappa-Minkowski spacetime by using representations of the corresponding deformed algebra in terms of undeformed Heisenberg-Weyl algebra. The deformed algebra consists of kappa-Poincare algebra extended with the generators of the deformed Weyl algebra. The part of deformed algebra, generated by rotation, boost and momentum generators, is described by the Hopf algebra structure. The approach used in our considerations is completely Lorentz covariant. We further use an adventages of this approach to consistently construct a star product which has a remarkable property that under integration sign it can be replaced by a standard pointwise multiplication, a property that was since known to hold for Moyal, but not also for kappa-Minkowski spacetime. This star product has also generalized trace and cyclic properties and the construction alone can be done in a simple and elegant way by considering a classical Dirac operator representation of the deformed algebra and by requiring it to...

  3. Spironolactone induces apoptosis and inhibits NF-kappaB independent of the mineralocorticoid receptor

    DEFF Research Database (Denmark)

    Sønder, Søren Ulrik Salling; Woetmann, Anders; Odum, Niels


    10 and 1000 muM, respectively, significantly increased both apoptosis and cell death. Production of inflammatory cytokines was significantly reduced by 3 to 30 muM SPIR and by 300 to 1000 muM SFZ. We also found that 0.4 muM SPIR and 300 muM SFZ significantly reduced the activity of NF-kappa......B, a transcription factor involved in both apoptosis and immunoinflammation. ALDO, the MR antagonist, eplerenone, and the SPIR metabolite, 7alpha-thiomethyl-spironolactone, slightly reduced NF-kappaB activity, but they did not interfere with SPIR's effect, showing that MR binding is not involved in SPIR......-induced suppression of NF-kappaB activity. Finally, phosphorylation of IkappaBalpha was also significantly reduced by SPIR. These results provide new insight into the apoptotic and anti-inflammatory effects of SPIR....

  4. Grafting of acrylamide onto kappa-carrageenan via {gamma}-irradiation: Optimization and swelling behavior

    Energy Technology Data Exchange (ETDEWEB)

    Rezanejade Bardajee, Ghasem [Department of Chemistry, Polymer Research Laboratory, Sharif University of Technology, Azadi Ave., P.O. Box 11365-9516, Tehran (Iran, Islamic Republic of); Pourjavadi, Ali [Department of Chemistry, Polymer Research Laboratory, Sharif University of Technology, Azadi Ave., P.O. Box 11365-9516, Tehran (Iran, Islamic Republic of)], E-mail:; Sheikh, Nasrin [Nuclear Science and Technology Research Institute, Radiation Applications Research School, Kargar Avenue, P.O. Box 11365-3486, Tehran (Iran, Islamic Republic of); Sadegh Amini-Fazl, Mohammad [Department of Chemistry, Polymer Research Laboratory, Sharif University of Technology, Azadi Ave., P.O. Box 11365-9516, Tehran (Iran, Islamic Republic of)


    The Taguchi method, a robust experimental design for optimization, was used for the synthesis of a superabsorbent hydrogel network using {gamma}-rays as an initiator, energy source and crosslinker at the same time. Nine different samples of superabsorbent hydrogels were prepared in various conditions from kappa-carrageenan ({kappa}C) and acrylamide by {gamma}-irradiation at room temperature. Considering the results of nine trials and according to analysis of variance (ANOVA), a new experimental condition with the concentrations of {kappa}C and acrylamide 1.5 g and 0.028 mol (2 g in total volume of 50 mL H{sub 2}O), respectively, as well as {gamma}-ray at the optimum total dose (7 kGy) was proposed. After preparing the desired hydrogels according to optimum condition, the swelling behavior of hydrogels in different media was investigated.

  5. Fradkin-Bacry-Ruegg-Souriau vector in kappa-deformed space-time

    CERN Document Server

    Guha, Partha; S, Zuhair N


    We study presence of an additional symmetry of a generic central potential in the $\\kappa$-space-time. An explicit construction of Fradkin and Bacry, Ruegg, Souriau (FBRS) for a central potential is carried out and the piece-wise conserved nature of the vector is established. We also extend the study to Kepler systems with a drag term, particularly Gorringe-Leach equation is generalized to the $\\kappa$-deformed space. The possibility of mapping Gorringe-Leach equation to an equation with out drag term is exploited in associating a similar conserved vector to system with a drag term. An extension of duality between two class of central potential is introduced in the $\\kappa$-deformed space and is used to investigate the duality existing between two class of Gorringe-Leach equations. All the results obtained can be retraced to the correct commutative limit as we let $a \\rightarrow 0$.

  6. Kappa-Casein Genotypic Frequencies in Holstein-Friesian Dairy Cattle in West Java Province

    Directory of Open Access Journals (Sweden)

    A. Anggraeni


    Full Text Available Kappa casein (ĸ-cn gene as one of the four casein genes commonly has two variant alleles. B allele is positively correlated with milk proteins, so potentially be used as MAS to improve milk protein content. This study aimed to identify genetic variation of the ĸ-casein gene in Holstein-Friesian (HF from several dairy regions in West Java. Blood samples were taken through jugular vein of lactating heifers and cows, from intensive managements under the Local Government Dairy Breeding Station - Cikole (BBPT Cikole-SP (82 hds, Embryo Transfer Station (BET (50 hds, and Eco Farm of Animal Science Faculty of Bogor Agricultural University (EcoFarm (20 hds; as well as from semi-intensive managements of small dairy farmers under the supervision of the North Lembang Cooperative Unit (KPSBU Lembang in two villages of Cilumber (98 hds and Pasar Kemis (92 hds. Blood samples were also taken via cocsigalis vein of AI (active and non active HF bulls at the two National AI Stations in Lembang (25 hds and Singosari (32 hds. Identification of genetic variation was by applying PCR-RFLP method. Three genotypes were identified, namely AA, AB, and BB, resulting two alleles of A and B. Results entirely showed that the frequencies of the BB HF female were very low, with the range of 0%-6% (vs AA genotype= 10%-54% and AB genotype= 46%-85%, despite of the relatively high frequency of the B allele over the A allele (23%-48% vs. 52%-77%. The low frequency of the observed BB females might be due to the limited AI active BB bulls used for services by the two national AI stations (0%-4%.

  7. Glutathione transferases kappa 1 and kappa 2 localize in peroxisomes and mitochondria, respectively, and are involved in lipid metabolism and respiration in Caenorhabditis elegans. (United States)

    Petit, Elise; Michelet, Xavier; Rauch, Claudine; Bertrand-Michel, Justine; Tercé, François; Legouis, Renaud; Morel, Fabrice


    To elucidate the function of kappa class glutathione transferases (GSTs) in multicellular organisms, their expression and silencing were investigated in Caenorhabditis elegans. In contrast with most vertebrates, which possess only one GST kappa gene, two distinct genes encoding GSTK-1 and GSTK-2 are present in the C. elegans genome. The amino acid sequences of GSTK-1 and GSTK-2 share around 30% similarity with the human hGSTK1 sequence and, like the human transferase, GSTK-1 contains a C-terminal peroxisomal targeting sequence. gstk-1 and gstk-2 genes show distinct developmental and tissue expression patterns. We show that GSTK-2 is localized in the mitochondria and expressed mainly in the pharynx, muscles and epidermis, whereas GSTK-1 is restricted to peroxisomes and expressed in the intestine, body wall muscles and epidermis. In order to determine the potential role(s) of GST kappa genes in C. elegans, specific silencing of the gstk-1 and gstk-2 genes was performed by an RNA interference approach. Knockdown of gstk-1 or gstk-2 had no apparent effect on C. elegans reproduction, development, locomotion or lifespan. By contrast, when biological functions (oxygen consumption and lipid metabolism) related to peroxisomes and/or mitochondria were investigated, we observed a significant decrease in respiration rate and a lower concentration of the monounsaturated fatty acid cis-vaccenic acid (18:1omega7) when worms were fed on bacteria expressing RNA interference targeting both gstk-1 and gstk-2. These results demonstrate that GST kappa, although not essential for the worm's life, may be involved in energetic and lipid metabolism, two functions related to mitochondria and peroxisomes.

  8. Amelioration of experimental autoimmune uveoretinitis (EAU) with an inhibitor of nuclear factor-kappaB (NF-kappaB), pyrrolidine dithiocarbamate. (United States)

    Kitamei, Hirokuni; Iwabuchi, Kazuya; Namba, Kenichi; Yoshida, Kazuhiko; Yanagawa, Yoshiki; Kitaichi, Nobuyoshi; Kitamura, Mizuki; Ohno, Shigeaki; Onoé, Kazunori


    Experimental autoimmune uveoretinitis (EAU) is a T helper type 1 cell-mediated autoimmune disease, which serves as a model of human chronic uveitis. In this model, cells of a monocyte/macrophage lineage and retinal antigen (Ag)-specific T cells infiltrate into the retina and cause inflammatory lesion, where proinflammatory cytokines and various stimuli activate a transcriptional factor, nuclear factor-kappaB (NF-kappaB), which modulates inflammation and enhances immune responses. In the present study, the therapeutic effect of administration of a NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC), was examined in a murine EAU model. It was shown that PDTC ameliorated the clinical symptoms of EAU mice and significantly reduced the histopathological score compared with those in untreated mice. mRNA expressions of tumor necrosis factor alpha and interleukin-1beta were suppressed in eyes of PDTC-treated EAU mice. However, when T cells from PDTC-treated EAU mice, Ag-presenting cells (APC), and the retinal Ag peptides were cocultured, these T cells showed the same level of proliferation as those from control mice. Furthermore, addition of PDTC in the culture of T cells from EAU mice, Ag, and APC completely abrogated the T cell-proliferative response and cytokine production. Pretreatment of Ag-primed T cells or APC with PDTC in vitro also reduced these responses. These results indicate that the inhibitory effect of PDTC is attributed mainly to the suppression of effector-phase responses including inflammation but not to the inhibition of T cell priming. Regulation of NF-kappaB pathway in the lesion could be a novel target for the successful control of uveoretinitis.

  9. Foxp3 represses retroviral transcription by targeting both NF-kappaB and CREB pathways.

    Directory of Open Access Journals (Sweden)


    Full Text Available Forkhead box (Fox/winged-helix transcription factors regulate multiple aspects of immune responsiveness and Foxp3 is recognized as an essential functional marker of regulatory T cells. Herein we describe downstream signaling pathways targeted by Foxp3 that may negatively impact retroviral pathogenesis. Overexpression of Foxp3 in HEK 293T and purified CD4+ T cells resulted in a dose-dependent and time-dependent decrease in basal levels of nuclear factor-kappaB (NF-kappaB activation. Deletion of the carboxyl-terminal forkhead (FKH domain, critical for nuclear localization and DNA-binding activity, abrogated the ability of Foxp3 to suppress NF-kappaB activity in HEK 293T cells, but not in Jurkat or primary human CD4+ T cells. We further demonstrate that Foxp3 suppressed the transcription of two human retroviral promoters (HIV-1 and human T cell lymphotropic virus type I [HTLV-I] utilizing NF-kappaB-dependent and NF-kappaB-independent mechanisms. Examination of the latter identified the cAMP-responsive element binding protein (CREB pathway as a target of Foxp3. Finally, comparison of the percent Foxp3+CD4+CD25+ T cells to the HTLV-I proviral load in HTLV-I-infected asymptomatic carriers and patients with HTLV-I-associated myelopathy/tropical spastic paraparesis suggested that high Foxp3 expression is associated with low proviral load and absence of disease. These results suggest an expanded role for Foxp3 in regulating NF-kappaB- and CREB-dependent cellular and viral gene expression.

  10. Immunoglobulin gene expression and regulation of rearrangement in kappa transgenic mice

    Energy Technology Data Exchange (ETDEWEB)

    Ritchie, K.A.


    Transgenic mice were produced by microinjection of the functionally rearranged immunoglobulin kappa gene from the myeloma MOPC-21 into the male pronucleus of fertilized mouse eggs, and implantation of the microinjected embryos into foster mothers. Mice that integrated the injected gene were detected by hybridizing tail DNA dots with radioactively labelled pBR322 plasmid DNA, which detects pBR322 sequences left as a tag on the microinjected DNA. Mice that integrated the injected gene (six males) were mated and the DNA, RNA and serum kappa chains of their offspring were analyzed. A rabbit anti-mouse kappa chain antiserum was also produced for use in detection of mouse kappa chains on protein blots. Hybridomas were produced from the spleen cells of these kappa transgenic mice to immortalize representative B cells and to investigate expression of the transgenic kappa gene, its effect on allelic exclusion, and its effect on the control of light chain gene rearrangement and expression. The results show that the microinjected DNA is integrated as concatamers in unique single or, rarely, two separate sites in the genome. The concatamers are composed of several copies (16 to 64) of injected DNA arranged in a head to tail fashion. The transgene is expressed into protein normally and in a tissue specific fashion. For the first time in these transgenic mice, all tissues contain a functionally rearranged and potentially expressible immunoglobulin gene. The transgene is expressed only in B cells and not in hepatocytes, for example. This indicates that rearrangement of immunoglobulin genes is necessary but not sufficient for the tissue specific expression of these genes by B cells.

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

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


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

  12. Public Values

    DEFF Research Database (Denmark)

    Beck Jørgensen, Torben; Rutgers, Mark R.


    administration is approached in terms of processes guided or restricted by public values and as public value creating: public management and public policy-making are both concerned with establishing, following and realizing public values. To study public values a broad perspective is needed. The article suggest......This article provides the introduction to a symposium on contemporary public values research. It is argued that the contribution to this symposium represent a Public Values Perspective, distinct from other specific lines of research that also use public value as a core concept. Public...... a research agenda for this encompasing kind of public values research. Finally the contributions to the symposium are introduced....

  13. Range Selection and Median

    DEFF Research Database (Denmark)

    Jørgensen, Allan Grønlund; Larsen, Kasper Green


    and several natural special cases thereof. The rst special case is known as range median, which arises when k is xed to b(j 􀀀 i + 1)=2c. The second case, denoted prex selection, arises when i is xed to 0. Finally, we also consider the bounded rank prex selection problem and the xed rank range......Range selection is the problem of preprocessing an input array A of n unique integers, such that given a query (i; j; k), one can report the k'th smallest integer in the subarray A[i];A[i+1]; : : : ;A[j]. In this paper we consider static data structures in the word-RAM for range selection...... selection problem. In the former, data structures must support prex selection queries under the assumption that k for some value n given at construction time, while in the latter, data structures must support range selection queries where k is xed beforehand for all queries. We prove cell probe lower bounds...

  14. IkappaBalpha deficiency results in a sustained NF-kappaB response and severe widespread dermatitis in mice. (United States)

    Klement, J F; Rice, N R; Car, B D; Abbondanzo, S J; Powers, G D; Bhatt, P H; Chen, C H; Rosen, C A; Stewart, C L


    The ubiquitous transcription factor NF-kappaB is an essential component in signal transduction pathways, in inflammation, and in the immune response. NF-kappaB is maintained in an inactive state in the cytoplasm by protein-protein interaction with IkappaBalpha. Upon stimulation, rapid degradation of IkappaBalpha allows nuclear translocation of NF-kappaB. To study the importance of IkappaBalpha in signal transduction, IkappaBalpha-deficient mice were derived by gene targeting. Cultured fibroblasts derived from IkappaBalpha-deficient embryos exhibit levels of NF-kappaB1, NF-kappaB2, RelA, c-Rel, and IkappaBbeta similar to those of wild-type fibroblasts. A failure to increase nuclear levels of NF-kappaB indicates that cytoplasmic retention of NF-kappaB may be compensated for by other IkappaB proteins. Treatment of wild-type cells with tumor necrosis factor alpha (TNF-alpha) resulted in rapid, transient nuclear localization of NF-kappaB. IkappaBalpha-deficient fibroblasts are also TNF-alpha responsive, but nuclear localization of NF-kappaB is prolonged, thus demonstrating that a major irreplaceable function Of IkappaBalpha is termination of the NF-kappaB response. Consistent with these observations, and with IkappaBalpha and NF-kappaB's role in regulating inflammatory and immune responses, is the normal development Of IkappaBalpha-deficient mice. However, growth ceases 3 days after birth and death usually occurs at 7 to 10 days of age. An increased percentage of monocytes/macrophages was detected in spleen cells taken from 5-, 7-, and 9-day-old pups. Death is accompanied by severe widespread dermatitis and increased levels of TNF-alpha mRNA in the skin. PMID:8628301

  15. Low Reynolds number kappa-epsilon and empirical transition models for oscillatory pipe flow and heat transfer (United States)

    Bauer, Christopher


    Stirling engine heat exchangers are shell-and-tube type with oscillatory flow (zero-mean velocity) for the inner fluid. This heat transfer process involves laminar-transition turbulent flow motions under oscillatory flow conditions. A low Reynolds number kappa-epsilon model, (Lam-Bremhorst form), was utilized in the present study to simulate fluid flow and heat transfer in a circular tube. An empirical transition model was used to activate the low Reynolds number k-e model at the appropriate time within the cycle for a given axial location within the tube. The computational results were compared with experimental flow and heat transfer data for: (1) velocity profiles, (2) kinetic energy of turbulence, (3) skin friction factor, (4) temperature profiles, and (5) wall heat flux. The experimental data were obtained for flow in a tube (38 mm diameter and 60 diameter long), with the maximum Reynolds number based on velocity being Re(sub max) = 11840, a dimensionless frequency (Valensi number) of Va = 80.2, at three axial locations X/D = 16, 30 and 44. The agreement between the computations and the experiment is excellent in the laminar portion of the cycle and good in the turbulent portion. Moreover, the location of transition was predicted accurately. The Low Reynolds Number kappa-epsilon model, together with an empirical transition model, is proposed herein to generate the wall heat flux values at different operating parameters than the experimental conditions. Those computational data can be used for testing the much simpler and less accurate one dimensional models utilized in 1-D Stirling Engine design codes.

  16. Effects of salvinorin A, a kappa-opioid hallucinogen, on a neuroendocrine biomarker assay in nonhuman primates with high kappa-receptor homology to humans. (United States)

    Butelman, Eduardo R; Mandau, Marek; Tidgewell, Kevin; Prisinzano, Thomas E; Yuferov, Vadim; Kreek, Mary Jeanne


    This study focused on the in vivo effects of the kappa-opioid hallucinogen salvinorin A, derived from the plant Salvia divinorum. The effects of salvinorin A (0.0032-0.056 mg/kg i.v.) were studied in a neuroendocrine biomarker assay of the anterior pituitary hormone prolactin in gonadally intact, adult male and female rhesus monkeys (n = 4 each). Salvinorin A produced dose- and time-dependent neuroendocrine effects, similar to the synthetic high-efficacy kappa-agonist U69,593 ((+)-(5alpha,7 alpha,8beta)-N-methyl-N-[7-(1-pyrrolidiniyl)-1-oxaspiro[4.5]dec-8yl]-benzeneacetamide), but of shorter duration than the latter. Salvinorin A was approximately equipotent to U69,593 in this endpoint (salvinorin A ED50, 0.015 mg/kg; U69,593 ED(50), 0.0098 mg/kg). The effects of i.v. salvinorin A were not prevented by a small dose of the opioid antagonist nalmefene (0.01 mg/kg s.c.) but were prevented by a larger dose of nalmefene (0.1 mg/kg); the latter nalmefene dose is sufficient to produce kappa-antagonist effects in this species. In contrast, the 5HT2 receptor antagonist ketanserin (0.1 mg/kg i.m.) did not prevent the effects of salvinorin A. As expected, the neuroendocrine effects of salvinorin A (0.0032 mg/kg i.v.) were more robust in female than in male subjects. Related studies focused on full-length cloning of the coding region of the rhesus monkey kappa-opioid receptor (OPRK1) gene and revealed a high homology of the nonhuman primate OPRK1 gene compared with the human OPRK1 gene, including particular C-terminal residues thought to be involved in receptor desensitization and internalization. The present studies indicate that the hallucinogen salvinorin A acts as a high-efficacy kappa-agonist in nonhuman primates in a translationally viable neuroendocrine biomarker assay.

  17. Effect of Helicobacterpylori cdrA on interleukin-8 secretions and nuclear factor kappa B activation

    Institute of Scientific and Technical Information of China (English)

    Hiroaki Takeuchi; Mikio Kamioka; Norihito Morimoto; Tetsuro Sugiura; Ya-Nan Zhang; Dawn A Israel; Richard M Peek Jr; Hideo Yanai


    AIM: To investigate genetic diversity of Helicobacter pylori (H. pylori) cell division-related gene A (cdrA) and its effect on the host response. METHODS: Inactivation of H. pylori cdrA, which is involved in cell division and morphological elongation, has a role in chronic persistent infections. Genetic property of H. pylori cdrA was evaluated using polymerase chain reaction and sequencing in 128 (77 American and 51 Japanese) clinical isolates obtained from 48 and 51 patients, respectively. Enzyme-linked immunosorbent assay was performed to measure interleukin-8 (IL-8) secretion with gadtric biopsy specimens obtained from American patients colonized with cdrA-positive or -negative strains and AGS cells co-cultured with wild-type HPK5 (cdrA-positive) or its derivative HPKT510 (cdrA-disruptant). Furthermore, the cytotoxin-associated gene A (cagA) status (translocation and phosphorylation) and kinetics of transcription factors [nuclear factor-kappa B (NF-κB) and inhibition kappa B] were investigated in AGS cells co-cultured with HPK5, HPKT510 and its derivative HPK5CA (cagAdisruptant) by western blotting analysis with immunoprecipitation. RESULTS: Genetic diversity of the H. pylori cdrA gene demonstrated that the cdrA status segregated into two categories including four allele types, cdrA-positive (allele types; Ⅰ and Ⅱ) and cdrA-negative (allele types; Ⅲ and Ⅳ) categories, respectively. Almost all Japanese isolates were cdrA -positive (Ⅰ: 7.8% and Ⅱ: 90.2%), whereas 16.9% of American isolates were cdrA -positive (Ⅱ) and 83.1% were cdrA -negative (Ⅲ: 37.7% and Ⅳ: 45.5%), indicating extended diversity of cdrA in individual American isolates. Comparison of each isolate from different regions (antrum and corpus) in the stomach of 29 Americans revealed that cdrA status was identical in both isolates from different regions in 17 cases. However, 12 cases had a different cdrA allele and 6 of them exhibited a different cdrA category between two regions in

  18. Activation of nuclear factor-kappa B via endogenous tumor necrosis factor alpha regulates survival of axotomized adult sensory neurons

    NARCIS (Netherlands)

    Fernyhough, P; Smith, DR; Schapansky, J; Van Der Ploeg, R; Gardiner, NJ; Tweed, CW; Kontos, A; Freeman, L; Purves-Tyson, TD; Glazner, GW


    Embryonic dorsal root ganglion (DRG) neurons die after axonal damage in vivo, and cultured embryonic DRG neurons require exogenous neurotrophic factors that activate the neuroprotective transcription factor nuclear factor-kappaB(NF-kappaB) for survival. In contrast, adult DRG neurons survive permane

  19. DMPD: Turning NF-kappaB and IRFs on and off in DC. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18534908 Turning NF-kappaB and IRFs on and off in DC. Kaisho T, Tanaka T. Trends Im... on and off in DC. PubmedID 18534908 Title Turning NF-kappaB and IRFs on and off in DC. Authors Kaisho T, Tanaka T. Publication Trend

  20. DMPD: Nuclear factor-kappaB: activation and regulation during toll-like receptorsignaling. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17349209 Nuclear factor-kappaB: activation and regulation during toll-like receptor...signaling. Carmody RJ, Chen YH. Cell Mol Immunol. 2007 Feb;4(1):31-41. (.png) (.svg) (.html) (.csml) Show Nuclear fact...or-kappaB: activation and regulation during toll-like receptorsignaling. PubmedID 17349209 Title Nuclear fact

  1. Development of a cell death-based method for the screening of nuclear factor-kappaB inhibitors. (United States)

    Chopra, Puneet; Bajpai, Malini; Dastidar, Sunanda G; Ray, Abhijit


    Nuclear factor kappa B (NF-kappaB) plays a significant role in immunity and inflammation and represents a first choice as pharmacological target for anti-inflammatory therapy. However, research in this field has been hampered by the fact that no convenient assay suitable for large-scale screening procedures is available. The present study provides a cell death-based assay method for screening of nuclear factor-kappaB inhibitors. In this study, we observed that four distinct pharmacologic inhibitors of NF-kappaB, pyrrolidine dithiocarbamate (PDTC), N-tosyl-L-lysyl chloromethyl ketone (TPCK), genistein and BAY11-7082, resulted in the cell death of murine macrophages, J774A.1. DNA-binding experiments showed that lethal doses were consistent with those required for NF-kappaB inhibition. DNA fragmentation analysis showed that cell death is apoptotic in nature. Further studies suggested that NF-kappaB inhibitors induced apoptosis is independent of the involvement of other markers of cell death such as caspases and p38 MAP (Mitogen activated protein) kinase. From this study, we conclude that NF-kappaB activation may represent an important survival mechanism in macrophages. This study also provides a new cell-based screening method, as any compound that will inhibit NF-kappaB activity will result in the death of macrophages.

  2. NF-kappaB signaling mediates vascular smooth muscle endothelin type B receptor expression in resistance arteries

    DEFF Research Database (Denmark)

    Zheng, Jian-Pu; Zhang, Yaping; Edvinsson, Lars


    Vascular smooth muscle cells (SMC) endothelin type B (ET(B)) receptor upregulation results in strong vasoconstriction and reduction of local blood flow. We hypothesizes that the underlying molecular mechanisms involve transcriptional factor nuclear factor-kappaB (NF-kappaB) pathway. ET(B) receptor...

  3. NF kappa B activity and target gene expression in the rat brain after one and two exposures to ionizing radiation. (United States)

    Raju, U; Gumin, G J; Tofilon, P J


    The central nervous system injury that can result after radiotherapy has been suggested to involve induced gene expression and cytokine production. We have previously shown that irradiation of primary cultures of rat astrocytes results in the activation of NF kappa B. To determine whether such an effect also occurs in vivo, NF kappa B activity was analyzed in the cerebral cortex of the rat brain after whole body irradiation. After a single dose of 15 Gy, NF kappa B activity was increased by 2 h postirradiation, returning to unirradiated levels by 8 hours. The increase was dose-dependent beginning at 2 Gy and continuing to at least 22.5 Gy. NF kappa B activity in the irradiated cortex was not accompanied by I kappa B alpha degradation. When 7.5 Gy was delivered 24 h before the 15 Gy, the increase in NF kappa B activity after 15 Gy was significantly reduced. These results suggest that an initial exposure to radiation induced a refractory period in the brain during which the susceptibility of NF kappa B to activation by subsequent irradiation was significantly reduced. This period of reduced sensitivity to radiation was also apparent for the induction of the NF kappa B-regulated cytokines IL-1 beta, IL-6, and TNF alpha.

  4. DMPD: Dual role of oxidized LDL on the NF-kappaB signaling pathway. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15346645 Dual role of oxidized LDL on the NF-kappaB signaling pathway. Robbesyn F, ...Salvayre R, Negre-Salvayre A. Free Radic Res. 2004 Jun;38(6):541-51. (.png) (.svg) (.html) (.csml) Show Dual role... of oxidized LDL on the NF-kappaB signaling pathway. PubmedID 15346645 Title Dual role of oxidized LDL

  5. Activation of nuclear factor-kappa B via endogenous tumor necrosis factor alpha regulates survival of axotomized adult sensory neurons

    NARCIS (Netherlands)

    Fernyhough, P; Smith, DR; Schapansky, J; Van Der Ploeg, R; Gardiner, NJ; Tweed, CW; Kontos, A; Freeman, L; Purves-Tyson, TD; Glazner, GW


    Embryonic dorsal root ganglion (DRG) neurons die after axonal damage in vivo, and cultured embryonic DRG neurons require exogenous neurotrophic factors that activate the neuroprotective transcription factor nuclear factor-kappaB(NF-kappaB) for survival. In contrast, adult DRG neurons survive

  6. Pim-2 activates API-5 to inhibit the apoptosis of hepatocellular carcinoma cells through NF-kappaB pathway. (United States)

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


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

  7. 非小细胞肺癌中NF-kappa B的表达与凋亡的关系%The Relationship between NF-kappa B and Apoptosis in Non-Small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    马建群; 张真发; 徐世东


    目的:研究核因子kappa B(nuclear factor kappa B,NF-kappa B)在非小细胞肺癌中的表达,探讨不同NF-kappa B表达的非小细胞的凋亡率,明确NF-kappa B在非小细胞肺癌中的临床意义.方法:应用Western blot检测了45例从2005年10月到2005年12月手术切除的非小细胞肺癌的新鲜标本,并用Tunel法测其凋亡率.结果:在45例患者中,NF-Kappa B的相对量是0.604 7±0.357 2,而且分化差的非小细胞肺癌中的NF-kappa B的表达比分化好的非小细胞肺癌高(P<0.05);在NF-kappa B高表达中肺癌细胞的凋亡率为56.4%,而在低表达中则为76.7%(P<0.05).结论:NF-kappa B的表达与非小细胞肺癌的分化相关,在非小细胞肺癌中,NF-kappa B抑制凋亡,并在非小细胞肺癌的形成和发展中起重要作用,或许可以作为基因治疗的靶点为非小细胞肺癌的诊治提供新的思路.


    Directory of Open Access Journals (Sweden)

    ST. Motameni


    Full Text Available In the past, health planning in Iran has been carried out in the context of short-range economic plans. Although this mechanism has helped a great deal in the achievement of certain health plans however, the said scheme has been short in meeting the health objectives on a comprehensive basis. Most often, the heath programs have lost their values to the priority and cost effectiveness of economic plans. A brief review of heath planning in the past shows that the second development plan has been devoted to the establishment of new hospitals on a scattered pattern. The development of a coordinated hospital and health center system has been accepted and partly implemented during the third plan period. In the fourth plan the whole direction has changed towards the de­velopment of private hospitals on profit making basis, and now the fifth plan calls for the regionalized hospital system. Thus, one can say that the past twenty years have been spent to the experimentation of different schemes with­out a real long-range goal. In the past decade the World Health Organization has ventured in the development of health planning principles, but most of the efforts have been devoted to the short-range planning. The long-range health planning is not only a new look to the prin­ciples of planning, but a thorough examination of the time factor in health planning.

  9. Creating comparability among reliability coefficients: the case of Cronbach alpha and Cohen kappa. (United States)

    Becker, G


    Cronbach alpha and Cohen kappa were compared and found to differ along two major facets. A fourfold classification system based on these facets clarifies the double contrast and produces a common metric allowing direct comparability. A new estimator, coefficient beta, is introduced in the process and is presented as a complement to coefficient alpha in estimating the psychometric properties of test scores and ratings.

  10. Testing Patterned Hypotheses in Multi-Way Contingency Tables Using Weighted Kappa and Weighted Chi Square (United States)

    Ross, Donald C.


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

  11. A star forming ring around Kappa Ori 250 pc from the Sun

    CERN Document Server

    Pillitteri, I; Megeath, S T


    X-rays are a powerful probe of activity in early stages of star formation. They allow us to identify young stars even after they have lost the IR signatures of circumstellar disks and provide constraints on their distance. Here we report on XMM-Newton observations which detect 121 young stellar objects (YSOs) in two fields between L1641S and $\\kappa$ Ori. These observations extend the Survey of Orion A with XMM and Spitzer (SOXS). The YSOs are contained in a ring of gas and dust apparent at millimeter wavelengths, and in far-IR and near-IR surveys. The X-ray luminosity function of the young stellar objects detected in the two fields indicates a distance of 250-280 pc, much closer than the Orion A cloud and similar to distance estimates of $\\kappa$ Ori. We propose that the ring is a 5-8 pc diameter shell that has been swept up by $\\kappa$ Ori. This ring contains several groups of stars detected by Spitzer and WISE including one surrounding the Herbig Ae/Be stars V1818 Ori. In this interpretation, the $\\kappa$ ...

  12. Kappa Opioid Receptors Mediate where Fear Is Expressed Following Extinction Training (United States)

    Cole, Sindy; Richardson, Rick; McNally, Gavan P.


    Six experiments used a within-subjects renewal design to examine the involvement of kappa opioid receptors (KORs) in regulating the expression and recovery of extinguished fear. Rats were trained to fear a tone conditioned stimulus (CS) via pairings with foot shock in a distinctive context (A). This was followed by extinction training of the CS in…

  13. Role of Human DNA Polymerase kappa in Extension Opposite from a cis-syn Thymine Dimer

    Energy Technology Data Exchange (ETDEWEB)

    R Vasquez-Del Carpio; T Silverstein; S Lone; R Johnson; L Prakash; S Prakash; A Aggarwal


    Exposure of DNA to UV radiation causes covalent linkages between adjacent pyrimidines. The most common lesion found in DNA from these UV-induced linkages is the cis-syn cyclobutane pyrimidine dimer. Human DNA polymerase {Kappa} (Pol{Kappa}), a member of the Y-family of DNA polymerases, is unable to insert nucleotides opposite the 3'T of a cis-syn T-T dimer, but it can efficiently extend from a nucleotide inserted opposite the 3'T of the dimer by another DNA polymerase. We present here the structure of human Pol{Kappa} in the act of inserting a nucleotide opposite the 5'T of the cis-syn T-T dimer. The structure reveals a constrained active-site cleft that is unable to accommodate the 3'T of a cis-syn T-T dimer but is remarkably well adapted to accommodate the 5'T via Watson-Crick base pairing, in accord with a proposed role for Pol{Kappa} in the extension reaction opposite from cyclobutane pyrimidine dimers in vivo.

  14. Changes of mu and kappa opioid receptors in cathartic colon of rat

    Institute of Scientific and Technical Information of China (English)

    LIU Bao-hua; MO Ping; JIA Hou-jun; LI Chun-xue; ZHANG Sheng-ben


    Objective: To oberve the changes of mu and kappa opioid receptors in the cathartic colon of rat, and to clarify that whether opioid receptors accounts for the occurrence of slow trait constipation (STC). Methods: The cathartiic colon model of rat was made by feeding with laxatives. The activity of mu and kappa opioid receptors in the cathartic colon of rat was measured by radio-ligand binding assay. Results: Compared with the control group, the maximal binding capacity (Bmax) and affinity(Kd) of mu opioid receptor in cathartic colon group were significantly increased (207. 00 ± 22. 90 fmol/mg·p vs 82. 00 ± 14.23 fmol/mg· p, P < 0.01 ;3.30 ± 0.45 mmol/L vs 2.40 ± 0.57 mmol/L, P < 0.05). The maximal binding capacity of kappa opioid receptor also showed a great increase (957. 00 ± 102. 41 fmol/mg· p vs 459.00 ± 52.41 fmol/mg·p, P < 0.01 ), but no significant difference of affinity was found between the two groups. Conclsion: The mu and kappa opioid receptors may be involved in the functional disorders of cathartic colon.

  15. Modulation of age-related NF-kappaB activation by dietary zingerone via MAPK pathway. (United States)

    Kim, Mi Kyung; Chung, Sang Woon; Kim, Dae Hyun; Kim, Ji Min; Lee, Eun Kyeong; Kim, Ji Young; Ha, Young Mi; Kim, Yun Hee; No, Jae-Kyung; Chung, Hye Sun; Park, Kun-Young; Rhee, Sook Hee; Choi, Jae Sue; Yu, Byung Pal; Yokozawa, Takako; Kim, Young Jin; Chung, Hae Young


    Zingerone, a major component found in ginger root, has been known as anti-mutagenic and anti-carcinogenic activities that are often associated with its anti-oxidative and anti-inflammatory activities. In recent studies, we examined molecular mechanism of zingerone treatment on pro-inflammatory NF-kappaB activation via the redox-related NIK/IKK and MAPK pathways. Action mechanism of zingerone on NF-kappaB signaling was investigated in aged rat kidney and endothelial cells. The results showed that zingerone had not only the antioxidant effect by constitutive suppression of ROS, but also anti-inflammatory effects by suppression of nuclear factor (NF)-kappaB activation in aged rat. In addition, zingerone treatment suppressed gene activation of pro-inflammatory enzymes, COX-2 and iNOS, which were upregulated with aging through NF-kappaB activation and IKK/MAPK signaling pathway. These experiments strongly indicate that zingerone treatment exerts a beneficial efficacy by suppressing both oxidative stress and age-related inflammation through the modulation of several key pro-inflammatory genes and transcription factors. Thus, the significance of our findings is that the zingerone treatment may provide some preventive measure against chronic inflammatory conditions that underlie many age-related inflammatory diseases, such as metabolic syndrome, cardiovascular disease, dementia, arthritis, diabetes, osteoprosis, and cancers.

  16. Joint environmental policy making and sustainable practices for the cardboard production: case study: Smurfit Kappa

    NARCIS (Netherlands)

    Carpio-Aguilar, J.C.; Franco-Garcia, M.L.


    Purpose – This paper presents an analysis of the influence of “Joint Environmental Policy-making” (JEP) in the operation of the company Smurfit Kappa (SK) in The Netherlands, Austria and Denmark (NL&AD). The paper aims to answer the question: to what extend has different levels of jointness and volu

  17. Kappa Opioid Receptors Mediate where Fear Is Expressed Following Extinction Training (United States)

    Cole, Sindy; Richardson, Rick; McNally, Gavan P.


    Six experiments used a within-subjects renewal design to examine the involvement of kappa opioid receptors (KORs) in regulating the expression and recovery of extinguished fear. Rats were trained to fear a tone conditioned stimulus (CS) via pairings with foot shock in a distinctive context (A). This was followed by extinction training of the CS in…

  18. Results of using permanent magnets to suppress Josephson noise in the KAPPa SIS receiver (United States)

    Wheeler, Caleb H.; Neric, Marko; Groppi, Christopher E.; Underhill, Matthew; Mani, Hamdi; Weinreb, Sander; Russell, Damon S.; Kooi, Jacob W.; Lichtenberger, Arthur W.; Walker, Christopher K.; Kulesa, Craig


    We present the results from the magnetic field generation within the Kilopixel Array Pathfinder Project (KAPPa) instrument. The KAPPa instrument is a terahertz heterodyne receiver using a Superconducting-Insulating- Superconducting (SIS) mixers. To improve performance, SIS mixers require a magnetic field to suppress Josephson noise. The KAPPa test receiver can house a tunable electromagnet used to optimize the applied magnetic field. The receiver is also capable of accommodating a permanent magnet that applies a fixed field. Our permanent magnet design uses off-the-shelf neodymium permanent magnets and then reshapes the magnetic field using machined steel concentrators. These concentrators allow the use of an unmachined permanent magnet in the back of the detector block while two small posts provide the required magnetic field across the SIS junction in the detector cavity. The KAPPa test receiver is uniquely suited to compare the permanent magnet and electromagnet receiver performance. The current work includes our design of a `U' shaped permanent magnet, the testing and calibration procedure for the permanent magnet, and the overall results of the performance comparison between the electromagnet and the permanent magnet counterpart.

  19. CNK1 promotes invasion of cancer cells through NF-kappaB-dependent signaling. (United States)

    Fritz, Rafael D; Radziwill, Gerald


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

  20. Apple, Cherry, and Blackcurrant Increases Nuclear Factor Kappa B Activation in Liver of Transgenic Mice

    DEFF Research Database (Denmark)

    Balstad, Trude; Paur, Ingvild; Poulsen, Morten


    Nuclear factor kappa B (NF-B) is essential in normal physiology, and several human disorders involve inappropriate regulation of NF-B. Diets dominated by plant-based foods protect against chronic diseases, and several food derived compounds have been identified as promising NF-B modulators. We...

  1. Optimisation of in silico derived 2-aminobenzimidazole hits as unprecedented selective kappa opioid receptor agonists

    DEFF Research Database (Denmark)

    Sasmal, Pradip K; Krishna, C Vamsee; Sudheerkumar Adabala, S


    Kappa opioid receptor (KOR) is an important mediator of pain signaling and it is targeted for the treatment of various pains. Pharmacophore based mining of databases led to the identification of 2-aminobenzimidazole derivative as KOR agonists with selectivity over the other opioid receptors DOR...

  2. Constant region of a kappa III immunoglobulin light chain as a major AL-amyloid protein

    DEFF Research Database (Denmark)

    Engvig, J P; Olsen, K E; Gislefoss, R E


    and the corresponding AL protein as a kappa III immunoglobulin light chain from material of a patient with systemic AL-amyloidosis presenting as a local inguinal tumour. The two proteins showed some unique features. The major part of the AL amyloid fibril protein consisted of C-terminal fragments of the Bence...

  3. Ion-acoustic cnoidal waves in plasmas with warm ions and kappa distributed electrons and positrons

    Energy Technology Data Exchange (ETDEWEB)

    Kaladze, T. [Department of Physics, Government College University (GCU), Lahore 54000 (Pakistan); I.Vekua Institute of Applied Mathematics, Tbilisi State University, 0186 Georgia (United States); Mahmood, S., E-mail: [Theoretical Physics Division (TPD), PINSTECH P.O. Nilore Islamabad 44000 (Pakistan); National Center for Physics (NCP), Quaid-i-Azam University Campus, Shahdra Valley Road, Islamabad 44000 (Pakistan)


    Electrostatic ion-acoustic periodic (cnoidal) waves and solitons in unmagnetized electron-positron-ion (EPI) plasmas with warm ions and kappa distributed electrons and positrons are investigated. Using the reductive perturbation method, the Korteweg-de Vries (KdV) equation is derived with appropriate boundary conditions for periodic waves. The corresponding analytical and various numerical solutions are presented with Sagdeev potential approach. Differences between the results caused by the kappa and Maxwell distributions are emphasized. It is revealed that only hump (compressive) structures of the cnoidal waves and solitons are formed. It is shown that amplitudes of the cnoidal waves and solitons are reduced in an EPI plasma case in comparison with the ordinary electron-ion plasmas. The effects caused by the temperature variations of the warm ions are also discussed. It is obtained that the amplitude of the cnoidal waves and solitons decreases for a kappa distributed (nonthermal) electrons and positrons plasma case in comparison with the Maxwellian distributed (thermal) electrons and positrons EPI plasmas. The existence of kappa distributed particles leads to decreasing of ion-acoustic frequency up to thermal ions frequency.

  4. Joint environmental policy making and sustainable practices for the cardboard production: case study: Smurfit Kappa

    NARCIS (Netherlands)

    Carpio-Aguilar, J.C.; Franco Garcia, Maria Maria


    Purpose – This paper presents an analysis of the influence of “Joint Environmental Policy-making” (JEP) in the operation of the company Smurfit Kappa (SK) in The Netherlands, Austria and Denmark (NL&AD). The paper aims to answer the question: to what extend has different levels of jointness and

  5. Kappa as a Parameter of a Symmetry Model for Rater Agreement. (United States)

    Schuster, Christof


    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)

  6. Studies on the adrenomedullary dependence of kappa-opioid agonist-induced diuresis in conscious rats. (United States)

    Borkowski, K. R.


    1. The dependence of kappa-opioid agonist-induced diuresis, upon an intact and functional adrenal medulla in conscious rats, was investigated in order to test the hypothesis that the diuresis is mediated by a blood-borne 'diuretic factor', of adrenomedullary origin, released by kappa-opioid receptor stimulation. 2. Confirming previous observations, adrenal demedullation significantly attenuated diuretic responses to the kappa-opioid agonists U50488H, ethylketocyclazocine (EKC) and tifluadom, but did not affect basal urine output, furosemide-induced diuresis or the antidiuretic response to the mu-opioid agonist, buprenorphine. Naloxone abolished U50488H-induced diuresis, confirming an involvement of opioid receptors. 3. Transfusion studies established that blood, from intact rats treated with U50488H, induced diuresis in intact and demedullated recipient rats, whether or not the recipients had been pretreated with naloxone. However, blood from demedullated rats treated with U50448H was unable to induce diuresis when administered to intact or demedullated recipients. 4. It is concluded that kappa-opioid agonist-induced diuresis is dependent upon an intact and functional adrenal medulla and appears to be mediated by a blood-borne 'diuretic factor' of adrenomedullary origin. PMID:2558758

  7. The Phi Delta Kappa At-Risk Scale: Its Composition, Meaning and Educational Implications. (United States)

    Freund, June; Lipka, Richard

    As part of a larger study by Phi Delta Kappa International (PDK), the PDK chapter in southeastern Kansas examined at-risk factors and "school effort" to address such factors in its geographical area. Data were obtained from the files of 270 "typical" students in Grades 4, 7, and 10 of three rural schools and from interviews with teachers,…

  8. Gauge theory on twisted kappa-Minkowski: old problems and possible solutions

    CERN Document Server

    Dimitrijevic, Marija; Pachol, Anna


    We review the application of twist deformation formalism and the construction of noncommutative gauge theory on kappa-Minkowski space-time. We compare two different types of twists: the Abelian and the Jordanian one. In each case we provide the twisted differential calculus and consider U(1) gauge theory. Different methods of obtaining a gauge invariant action and related problems are thoroughly discussed.

  9. Ion-acoustic cnoidal waves in plasmas with warm ions and kappa distributed electrons and positrons (United States)

    Kaladze, T.; Mahmood, S.


    Electrostatic ion-acoustic periodic (cnoidal) waves and solitons in unmagnetized electron-positron-ion (EPI) plasmas with warm ions and kappa distributed electrons and positrons are investigated. Using the reductive perturbation method, the Korteweg-de Vries (KdV) equation is derived with appropriate boundary conditions for periodic waves. The corresponding analytical and various numerical solutions are presented with Sagdeev potential approach. Differences between the results caused by the kappa and Maxwell distributions are emphasized. It is revealed that only hump (compressive) structures of the cnoidal waves and solitons are formed. It is shown that amplitudes of the cnoidal waves and solitons are reduced in an EPI plasma case in comparison with the ordinary electron-ion plasmas. The effects caused by the temperature variations of the warm ions are also discussed. It is obtained that the amplitude of the cnoidal waves and solitons decreases for a kappa distributed (nonthermal) electrons and positrons plasma case in comparison with the Maxwellian distributed (thermal) electrons and positrons EPI plasmas. The existence of kappa distributed particles leads to decreasing of ion-acoustic frequency up to thermal ions frequency.

  10. {kappa} state solutions of the Dirac equation for the Eckart potential with pseudospin and spin symmetry

    Energy Technology Data Exchange (ETDEWEB)

    Soylu, A [Department of Physics, Nigde University, 51350, Nigde (Turkey); Bayrak, O; Boztosun, I [Department of Physics, Erciyes University, 38039, Kayseri (Turkey)


    For any spin-orbit coupling term {kappa}, the analytical solutions of the Dirac equation for the Eckart potential are presented by using the asymptotic iteration method within the framework of the spin and pseudospin symmetry concept. The energy eigenvalues are obtained in the closed form by applying an approximation to the spin-orbit coupling potential.

  11. Transcription factor NF-kappaB as a potential biomarker for oxidative stress.

    NARCIS (Netherlands)

    van den Berg, R.; Haenen, G.R.M.M.; van den Berg, H.; Bast, A.


    Br J Nutr 2001 Aug;86 Suppl 1:S121-7 Related Articles, Books, LinkOut Transcription factor NF-kappaB as a potential biomarker for oxidative stress. van den Berg R, Haenen GR, van den Berg H, Bast A. TNO Nutrition and Food Research, P.O. Box 360, 3700 AJ Zeist, Netherlands. R.vandenberg@voeding.tno.n

  12. An NF-kappaB and slug regulatory loop active in early vertebrate mesoderm.

    Directory of Open Access Journals (Sweden)

    Chi Zhang

    Full Text Available BACKGROUND: In both Drosophila and the mouse, the zinc finger transcription factor Snail is required for mesoderm formation; its vertebrate paralog Slug (Snai2 appears to be required for neural crest formation in the chick and the clawed frog Xenopus laevis. Both Slug and Snail act to induce epithelial to mesenchymal transition (EMT and to suppress apoptosis. METHODOLOGY & PRINCIPLE FINDINGS: Morpholino-based loss of function studies indicate that Slug is required for the normal expression of both mesodermal and neural crest markers in X. laevis. Both phenotypes are rescued by injection of RNA encoding the anti-apoptotic protein Bcl-xL; Bcl-xL's effects are dependent upon IkappaB kinase-mediated activation of the bipartite transcription factor NF-kappaB. NF-kappaB, in turn, directly up-regulates levels of Slug and Snail RNAs. Slug indirectly up-regulates levels of RNAs encoding the NF-kappaB subunit proteins RelA, Rel2, and Rel3, and directly down-regulates levels of the pro-apopotic Caspase-9 RNA. CONCLUSIONS/SIGNIFICANCE: These studies reveal a Slug/Snail-NF-kappaB regulatory circuit, analogous to that present in the early Drosophila embryo, active during mesodermal formation in Xenopus. This is a regulatory interaction of significance both in development and in the course of inflammatory and metastatic disease.

  13. NF-kappaB-driven STAT2 and CCL2 expression in astrocytes in response to brain injury

    DEFF Research Database (Denmark)

    Khorooshi, Reza; Babcock, Alicia A; Owens, Trevor


    Tissue response to injury includes expression of genes encoding cytokines and chemokines. These regulate entry of immune cells to the injured tissue. The synthesis of many cytokines and chemokines involves NF-kappaB and signal transducers and activators of transcription (STAT). Injury to the CNS...... induces glial response. Astrocytes are the major glial population in the CNS. We examined expression of STATs and the chemokine CCL2 and their relationship to astroglial NF-kappaB signaling in the CNS following axonal transection. Double labeling with Mac-1/CD11b and glial fibrillary acidic protein......-regulation and phosphorylation were NF-kappaB -dependent since they did not occur in the lesion-reactive hippocampus of transgenic mice with specific inhibition of NF-kappaB activation in astrocytes. We further showed that lack of NF-kappaB signaling significantly reduced injury-induced CCL2 expression as well as leukocyte...

  14. TUCAN/CARDINAL and DRAL participate in a common pathway for modulation of NF-kappaB activation. (United States)

    Stilo, Romania; Leonardi, Antonio; Formisano, Luigi; Di Jeso, Bruno; Vito, Pasquale; Liguoro, Domenico


    Proteins containing the caspase recruiting domain (CARD) have emerged as critical regulators of different signal transduction pathways, including those controlling apoptosis and activation of necrosis factor (NF)-kappaB transcription factor. TUCAN/CARDINAL is a recently identified CARD-containing protein involved in regulation of caspases and NF-kappaB activation. We find that TUCAN/CARDINAL associates with DRAL, a p53-responsive gene implicated in induction of apoptosis. We also show that, whereas TUCAN/CARDINAL exerts a suppressive effect on NF-kappaB activity, expression of DRAL results in enhancement of NF-kappaB activation. Thus, our observations suggest that DRAL and TUCAN/CARDINAL may participate in a regulatory mechanism that coordinates cellular responses controlled by NF-kappaB transcription factor.

  15. Weight analysis of influencing factors of human angle Kappa%人眼Kappa角的影响因素权重分析

    Institute of Scientific and Technical Information of China (English)

    程丹; 徐菁菁; 保金华; 潘建东; 吕帆


    Background Angle Kappa is the angle between the pupillary axis and visual axis,and it is a major consideration in corneal refractive surgery and strabismic surgery.Researches showed that age and refractive status affect angle Kappa value,and additionally,the measuring results of angle Kappa are associated with instruments.Objective This study was to investigate and weight the influences of axial length,anterior chamber depth and corneal curvature to angle Kappa.Methods A cross-sectional study was designed.Fifty health volunteers were included from Dec 2009 to Aug 2010,with the age of 18-38 years and average diopter of-1.0 D and best corrected visual acuity of 1.0.The horizontal and vertical angle Kappa was binocular measured with a testing machine designed by laboratory of School of Optometry & Ophthalmology Wenzhou Medical University.IOLMaster was employed to measure the ocular axial length,anterior chamber depth and corneal curvature radius.A multiple linear regression model was established to analyze the influences of axial length,anterior chamber depth and corneal curvature radius to angle Kappa.Results An efficacious regression equation was established as Y =15.554-0.587X1+0.724X2+ 0.232X3 with the independent variables as axial length(X1),anterior chamber depth (X2),corneal curvature (X3) and dependent variable as horizontal angle Kappa (Y) (R =0.788,R2 =0.621,P =0.000).Horizontal angle Kappa showed a negative correlation with axial length (b1 =-0.587,β1 =-1.002,P =0.000) and a positive correlation with anterior chamber depth (b2 =0.724,β32 =0.296,P =0.030).No significant correlation was found between corneal curvature radius and horizontal angle Kappa (b3 =-0.232,β3 =-0.068,P=0.338).A new regression equation was Y =14.235-0.622X1 + 0.824X2 after removed the corneal curvature variable (R =0.786,R2=0.618,P =0.000),with a negative correlation between horizontal angle Kappa and axial length (b1 =-0.622,β1 =-1.062,P<0.05) or positive correlation between

  16. Quantitative enzymatic production of sialylated galactooligosaccharides with an engineered sialidase from Trypanosoma rangeli

    DEFF Research Database (Denmark)

    Zeuner, Birgitte; Holck, Jesper; Perna, Valentina


    be produced from κ(kappa)-casein glycomacropeptide (CGMP), a sialylated side stream component from cheese-making, by sialidase-catalyzed transsialylation. Using a rationally designed mutant of the sialidase from Trypanosoma rangeli, Tr13, with enhanced transsialylation activity, six different GOS preparations...

  17. On the effect of silicon and phosphorus during the precipitation of kappa-carbide in Iron-Manganese-Aluminium-Carbon alloys (United States)

    Bartlett, Laura Nicole

    Implementation of lightweight high manganese and aluminum steels for use in high energy absorbing applications requires a detailed knowledge of how alloying additions and impurities affect age hardening and high strain rate fracture properties. Dynamic fracture toughness is an important design criterion but has not been reported previously in these alloys. In addition, previous studies have shown that silicon and phosphorus increased the strength and aged hardness; however, the mechanism was unknown. This research mainly focuses on the effect of silicon and phosphorus on the precipitation of kappa-carbide and alloy partitioning during aging. Short range ordering, SRO, of Fe-Al-C into relative atomic positions described by the E21 superlattice structure preceded and occurred concurrent to spinodal decomposition. Short range diffusion of phosphorus increased the kinetics of ordering resulting in a decrease in the time required for subsequent spinodal decomposition and an increase the amplitude of carbon concentration with time. Silicon increased the strength and hardness as a result of increased carbon partitioning into the kappa-carbide during aging. Dynamic fracture toughness was found to depend upon aluminum and carbon. Increasing the amount of solid solution carbon increased the dynamic fracture toughness in solution treated specimens. However, increasing carbon in aged specimens increased the amount of kappa-carbide and produced brittle fracture. Additions of aluminum from three to nine weight percent decreased toughness regardless of the heat treatment. Dynamic fracture toughness was a strong function of AlN content. A good combination of high strength and dynamic toughness with a corresponding density reduction of 10 to 12% is obtained with aluminum additions between 6 and 7% and carbon below 1.2%.

  18. NF-kappaB activity marks cells engaged in receptor editing. (United States)

    Cadera, Emily J; Wan, Fengyi; Amin, Rupesh H; Nolla, Hector; Lenardo, Michael J; Schlissel, Mark S


    Because of the extreme diversity in immunoglobulin genes, tolerance mechanisms are necessary to ensure that B cells do not respond to self-antigens. One such tolerance mechanism is called receptor editing. If the B cell receptor (BCR) on an immature B cell recognizes self-antigen, it is down-regulated from the cell surface, and light chain gene rearrangement continues in an attempt to edit the autoreactive specificity. Analysis of a heterozygous mutant mouse in which the NF-kappaB-dependent IkappaB alpha gene was replaced with a lacZ (beta-gal) reporter complementary DNA (cDNA; IkappaB alpha(+/lacZ)) suggests a potential role for NF-kappaB in receptor editing. Sorted beta-gal(+) pre-B cells showed increased levels of various markers of receptor editing. In IkappaB alpha(+/lacZ) reporter mice expressing either innocuous or self-specific knocked in BCRs, beta-gal was preferentially expressed in pre-B cells from the mice with self-specific BCRs. Retroviral-mediated expression of a cDNA encoding an IkappaB alpha superrepressor in primary bone marrow cultures resulted in diminished germline kappa and rearranged lambda transcripts but similar levels of RAG expression as compared with controls. We found that IRF4 transcripts were up-regulated in beta-gal(+) pre-B cells. Because IRF4 is a target of NF-kappaB and is required for receptor editing, we suggest that NF-kappaB could be acting through IRF4 to regulate receptor editing.

  19. BHT blocks NF-kappaB activation and ethanol-induced brain damage. (United States)

    Crews, Fulton; Nixon, Kimberly; Kim, Daniel; Joseph, James; Shukitt-Hale, Barbara; Qin, Liya; Zou, Jian


    Binge ethanol administration causes corticolimbic brain damage that models alcoholic neurodegeneration. The mechanism of binge ethanol-induced degeneration is unknown, but is not simple glutamate-N-methyl-D-aspartate (NMDA) excitotoxicity. To test the hypothesis that oxidative stress and inflammation are mechanisms of binge ethanol-induced brain damage, we administered 4 antioxidants, e.g., butylated hydroxytoluene (BHT), ebselen (Eb), vitamin E (VE), and blueberry (BB) extract, during binge ethanol treatment and assessed various measures of neurodegeneration. Adult Sprague-Dawley rats were treated with intragastric ethanol 3 times per day (8-12 g/kg/d) alone or in combination with antioxidants or isocaloric diet for 4 days. Animals were killed, and brains were perfused and extracted for histochemical silver stain determination of brain damage, markers of neurogenesis, or other immunohistochemistry. Some animals were used for determination of nuclear factor kappa B (NF-kappaB)-DNA binding by electrophoretic mobility shift assay (EMSA) or for reverse transcription-polymerase chain reaction (RT-PCR) of cyclooxygenase 2 (COX2). Binge ethanol induced corticolimbic brain damage and reduced neurogenesis. Treatment with BHT reversed binge induced brain damage and blocked ethanol inhibition of neurogenesis in all regions studied. Interestingly, the other antioxidants studied, e.g., Eb, VE, and BB, did not protect against binge-induced brain damage. Binge ethanol treatment also caused microglia activation, increased NF-kappaB-DNA binding and COX2 expression. Butylated hydroxytoluene reduced binge-induced NF-kappaB-DNA binding and COX2 expression. Binge-induced brain damage and activation of NF-kappaB-DNA binding are blocked by BHT. These studies support a neuroinflammatory mechanism of binge ethanol-induced brain damage.

  20. TNF-alpha/IL-1/NF-kappaB transduction pathway in human cancer prostate. (United States)

    Royuela, M; Rodríguez-Berriguete, G; Fraile, B; Paniagua, R


    TNFalpha exerts apoptosis throughout an intracellular transduction pathway that involves the kinase proteins TRAF-2 (integration point of apoptotic and survival signals), ASK1 (pro-apoptotic protein), MEK-4 (p38 activator and metastasis suppressor gene), JNK (stress mitogen activated protein kinase) and the transcription factor AP-1. TNFalpha also exerts proliferation by p38 activation, or when TRAF-2 simultaneously induces the transcription factor NF-kappaB by NIK. NIK and p38 may also be activated by IL-1. P38 activated several transcription factors such as Elk-1, ATF-2 and NF-kappaB. NIK also may activate NF-kappaB. The aim of the present article was to evaluate the different components of this TNFalpha/IL-1 transduction pathway in human prostate carcinoma (PC) in comparison with normal human prostate. In prostate cancer, pro-apoptotic TNFalpha/AP-1 pathway is probably inactivated by different factors such as p21 (at ASK-1 level) and bcl-2 (at JNK level), or diverted towards p38 or NIK activation. IL-1alpha enhances proliferation through IL-1RI that activates either NIK or p38 transduction pathway. P38 and NIK activate different transcription factors related with cell proliferation and survival such as ATF-2, Elk-1 or NF-kappaB. In order to search a possible target to cancer prostate treatment we proposed that inhibition of several proinflamatory cytokines such as IL-1 and TNFalpha might be a possible target for PC treatment, because decrease the activity of all transduction pathway members that activate transcription factors as NF-kappaB, Elk-1 or ATF-2.

  1. Effects of age and sedentary lifestyle on skeletal muscle NF-kappaB signaling in men. (United States)

    Buford, Thomas W; Cooke, Matthew B; Manini, Todd M; Leeuwenburgh, Christiaan; Willoughby, Darryn S


    Nuclear factor kappa B (NF-kappaB) is a critical signaling molecule of disuse-induced skeletal muscle atrophy. However, few studies have carefully investigated whether similar pathways are modulated with physical activity and age. The present study examined lean mass, maximal force production, and skeletal muscle NF-kappaB signaling in 41 men categorized as sedentary (OS, N = 13, 63.85 +/- 6.59 year), physically active (OA, N = 14, 60.71 +/- 5.54 year), or young and sedentary (YS, N = 14, 21.35 +/- 3.84 year). Muscle tissue from the vastus lateralis was assayed for messenger RNA (mRNA) expression of the beta subunit of IkB kinase (IKKbeta), cytosolic protein content of phosphorylated inhibitor of kappa B alpha (pIKBalpha), and nuclear content of NF-kappaB subunits p50 and p65. When compared with YS, OS demonstrated age-related muscle atrophy and reduced isokinetic knee extension torque. Physical activity in older individuals preserved maximal isokinetic knee extension torque. OS muscle contained 50% more pIKBalpha than OA and 61% more pIKBalpha than YS. Furthermore, nuclear p65 was significantly elevated in OS compared with YS. OS muscle did not differ from either of the other two groups for nuclear p50 or for mRNA expression of IKKbeta. These results indicate that skeletal muscle content of nuclear-bound p65 is elevated by age in humans. The elevation in nuclear-bound p65 appears to be at least partially due to significant increases in pIKBalpha. A sedentary lifestyle appears to play some role in increased IKBalpha; however, further research is needed to identify downstream effects of this increase.

  2. Induction of nuclear translocation of NF-kappaB in epithelial cells by respirable mineral fibres. (United States)

    Brown, D M; Beswick, P H; Donaldson, K


    A panel of mineral fibres has been studied for their ability to cause translocation of the transcription factor NF-kappaB to the nucleus in A549 lung epithelial cells. On the basis of inhalation studies, three fibres were designated as being carcinogenic-amosite asbestos, silicon carbide and refractory ceramic fibre 1 (RCF1)-or non-carcinogenic-man-made vitreous fibre (MMVF10), Code 100/475 glass fibre, and RCF4. The experiments were carried out at equal fibre number. It was hypothesized that carcinogenic fibres have greater free radical activity than non-carcinogenic fibres and that an oxidative stress produced in the lung after inhalation of fibres could cause translocation of the transcription factor NF-kappaB to the nucleus, where transcription of pro-inflammatory genes such as cytokines could occur. It was demonstrated that a simple oxidant, hydrogen peroxide, caused translocation in a time- and dose-dependent manner. The three carcinogenic fibres produced a significant dose-dependent translocation of NF-kappaB to the nucleus, whereas the non-carcinogenic fibres did not. Silicon carbide fibres were the most potent of the pathogenic fibres. MMVF10 was the most potent of the non-pathogenic fibres, causing significant nuclear translocation of NF-kappaB at high fibre number. Using three antioxidants, curcumin, pyrrolidine dithiocarbamate, and Nacystelin, translocation caused by carcinogenic fibres could be significantly reduced. The present study shows that a short-term in vitro assay can discriminate between pathogenic and non-pathogenic fibres in terms of a key pro-inflammatory event in epithelial cells. The mechanism of the activation of NF-kappaB by pathogenic fibres and its general applicability to other fibre types remain to be determined.

  3. Zinc oxide particles induce inflammatory responses in vascular endothelial cells via NF-{kappa}B signaling

    Energy Technology Data Exchange (ETDEWEB)

    Tsou, Tsui-Chun, E-mail: [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Miaoli County, Taiwan (China); Yeh, Szu-Ching; Tsai, Feng-Yuan; Lin, Ho-Jane [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Miaoli County, Taiwan (China); Cheng, Tsun-Jen [Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University, Taipei, Taiwan (China); Chao, How-Ran [Department of Environmental Science and Engineering, National Pingtung University of Science and Technology, Neipu, Pingtung, Taiwan (China); Tai, Lin-Ai [Center for Nanomedicine Research, National Health Research Institutes, Zhunan, Miaoli County, Taiwan (China)


    This study investigated inflammatory effects of zinc oxide (ZnO) particles on vascular endothelial cells. The effects of 50 and 100-nm ZnO particles on human umbilical vein endothelial cells (HUVECs) were characterized by assaying cytotoxicity, cell proliferation, and glutathione levels. A marked drop in survival rate was observed when ZnO concentration was increased to 45 {mu}g/ml. ZnO concentrations of {<=}3 {mu}g/ml resulted in increased cell proliferation, while those of {<=}45 {mu}g/ml caused dose-dependent increases in oxidized glutathione levels. Treatments with ZnO concentrations {<=}45 {mu}g/ml were performed to determine the expression of intercellular adhesion molecule-1 (ICAM-1) protein, an indicator of vascular endothelium inflammation, revealing that ZnO particles induced a dose-dependent increase in ICAM-1 expression and marked increases in NF-{kappa}B reporter activity. Overexpression of I{kappa}B{alpha} completely inhibited ZnO-induced ICAM-1 expression, suggesting NF-{kappa}B plays a pivotal role in regulation of ZnO-induced inflammation in HUVECs. Additionally, TNF-{alpha}, a typical inflammatory cytokine, induced ICAM-1 expression in an NF-{kappa}B-dependent manner, and ZnO synergistically enhanced TNF-{alpha}-induced ICAM-1 expression. Both 50 and 100-nm ZnO particles agglomerated to similar size distributions. This study reveals an important role for ZnO in modulating inflammatory responses of vascular endothelial cells via NF-{kappa}B signaling, which could have important implications for treatments of vascular disease.

  4. The Importance of the Ubiquitous 'Kappa' Distributions in Space Plasmas (Invited) (United States)

    Scudder, J. D.; Karimabadi, H.


    The kappa model for f(v) was originally derived by Olbert (1966) to provide frugal but informative fits to observed particle fluxes from which moments of the underlying plasma could be extracted. Olbert's new fit parameter (kappa) allowed for the ambient plasma to possess reduced kurtosis, which a Gaussian does not. The universality of kappa can easily be overstated, since it cannot fit distributions with a heat flux which is generally important in astrophysical plasmas. Geophysically the frequent use of such a parametrization for the zeroth order energy distribution in the comoving frame acknowledges that the observed plasmas of nature are generally non-thermal, hence kurtotic, which for this author is their principal significance. A key question remains whether the analytically convenient kappa function's kurtotic form is required by the laws of physics, or rather a deft representative of all possible distributions with non-negligible kurtosis and other higher moments. This paper develops why the non-thermal kurtotic f(v) should generally be expected in astrophysical plasmas structured by gravity, driven by their tendency to achieve quasi-neutrality. It will demonstrate the essential role of runaway phenomena in the origin of this kurtosis while showing consistency with observables. This approach provides a rationale why such kurtotic distributions should occur without arguing what its precise shape should be, beyond possessing non-zero skewness and kurtosis. Initial results will be shown that the kappa model for such kurtotic distributions, while better than an Gaussian, may be too rigid to describe the non-thermal distributions of nature at all radial distances from the sun.

  5. Protein kinase C-associated kinase (PKK) mediates Bcl10-independent NF-kappa B activation induced by phorbol ester. (United States)

    Muto, Akihiro; Ruland, Jürgen; McAllister-Lucas, Linda M; Lucas, Peter C; Yamaoka, Shoji; Chen, Felicia F; Lin, Amy; Mak, Tak W; Núñez, Gabriel; Inohara, Naohiro


    Protein kinase C-associated kinase (PKK) is a recently described kinase of unknown function that was identified on the basis of its specific interaction with PKC beta. PKK contains N-terminal kinase and C-terminal ankyrin repeats domains linked to an intermediate region. Here we report that the kinase domain of PKK is highly homologous to that of two mediators of nuclear factor-kappa B (NF-kappa B) activation, RICK and RIP, but these related kinases have different C-terminal domains for binding to upstream factors. We find that expression of PKK, like RICK and RIP, induces NF-kappa B activation. Mutational analysis revealed that the kinase domain of PKK is essential for NF-kappa B activation, whereas replacement of serine residues in the putative activation loop did not affect the ability of PKK to activate NF-kappa B. A catalytic inactive PKK mutant inhibited NF-kappa B activation induced by phorbol ester and Ca(2+)-ionophore, but it did not block that mediated by tumor necrosis factor alpha, interleukin-1 beta, or Nod1. Inhibition of NF-kappa B activation by dominant negative PKK was reverted by co-expression of PKC beta I, suggesting a functional association between PKK and PKC beta I. PKK-mediated NF-kappa B activation required IKK alpha and IKK beta but not IKK gamma, the regulatory subunit of the IKK complex. Moreover, NF-kappa B activation induced by PKK was not inhibited by dominant negative Bimp1 and proceeded in the absence of Bcl10, two components of a recently described PKC signaling pathway. These results suggest that PKK is a member of the RICK/RIP family of kinases, which is involved in a PKC-activated NF-kappa B signaling pathway that is independent of Bcl10 and IKK gamma.

  6. Transglutaminase 2 gene ablation protects against renal ischemic injury by blocking constant NF-{kappa}B activation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dae-Seok [Cancer Cell and Molecular Biology Branch, Division of Cancer Biology, Research Institute, 111 Jungbalsan-ro, Ilsandong-gu, Goyang, Gyeonggi-do 410-769 (Korea, Republic of); Kim, Bora [Animal Sciences Branch, Research Institute, 111 Jungbalsan-ro, Ilsandong-gu, Goyang, Gyeonggi-do 410-769 (Korea, Republic of); Tahk, Hongmin [Department of Food and Nutrition, College of Human Ecology, Chung-Ang University, 72-1, Nae-ri, Daeduck-myun, Ansung, Gyeonggi-do 456-756 (Korea, Republic of); Kim, Dong-Hyun; Ahn, Eu-Ree [Cancer Cell and Molecular Biology Branch, Division of Cancer Biology, Research Institute, 111 Jungbalsan-ro, Ilsandong-gu, Goyang, Gyeonggi-do 410-769 (Korea, Republic of); Choi, Changsun [Department of Food and Nutrition, College of Human Ecology, Chung-Ang University, 72-1, Nae-ri, Daeduck-myun, Ansung, Gyeonggi-do 456-756 (Korea, Republic of); Jeon, Yoon; Park, Seo Young; Lee, Ho; Oh, Seung Hyun [Cancer Experimental Resources Branch, Division of Cancer Biology, Research Institute, 111 Jungbalsan-ro, Ilsandong-gu, Goyang, Gyeonggi-do 410-769 (Korea, Republic of); Kim, Soo-Youl, E-mail: [Cancer Cell and Molecular Biology Branch, Division of Cancer Biology, Research Institute, 111 Jungbalsan-ro, Ilsandong-gu, Goyang, Gyeonggi-do 410-769 (Korea, Republic of)


    Research highlights: {yields} No acute renal tubular necrotic lesions were found in TGase2{sup -/-} mice with ischemic kidney injury. {yields} NF-{kappa}B activation is reduced in TGase2{sup -/-} mice with ischemic kidney injury. {yields} Hypoxic stress did not increase NF-{kappa}B activity in MEFs from TGase2{sup -/-} mice. {yields} COX-2 induction is suppressed in TGase2{sup -/-} mice with ischemic kidney injury. -- Abstract: Transglutaminase 2 knockout (TGase2{sup -/-}) mice show significantly reduced inflammation with decreased myofibroblasts in a unilateral ureteral obstruction (UUO) model, but the mechanism remains to be clarified. Nuclear factor-{kappa}B (NF-{kappa}B) activation plays a major role in the progression of inflammation in an obstructive nephropathy model. However, the key factors extending the duration of NF-{kappa}B activation in UUO are not known. In several inflammatory diseases, we and others recently found that TGase 2 plays a key role in extending NF-{kappa}B activation, which contributes to the pathogenesis of disease. In the current study, we found that NF-{kappa}B activity in mouse embryogenic fibroblasts (MEFs) from TGase2{sup -/-} mice remained at the control level while the NF-{kappa}B activity of wild-type (WT) MEFs was highly increased under hypoxic stress. Using the obstructive nephropathy model, we found that NF-{kappa}B activity remained at the control level in TGase2{sup -/-} mouse kidney tissues, as measured by COX-2 expression, but was highly increased in WT tissues. We conclude that TGase 2 gene ablation reduces the duration of NF-{kappa}B activation in ischemic injury.

  7. Values Research (United States)


    horizontal vs. vertical. • According to the theory of Planned Behavior ( Ajzen , 1988, 2002) attitude, subjective norms and perceived control...determines intention which may end in behavior . 7 Defining Human Values Cross-cultural theories on values emerged in the 80s developed by three main...attitudes with social structure. 4 Defining Human Values • According to Parsons (Parsons & Shils, 1951), values instigate behavior . • In line

  8. Long-range Video EEG Monitoring Diagnostic Value of the Onset of Disease%录像脑电图长程监测对发作性疾病的诊断价值

    Institute of Scientific and Technical Information of China (English)

    魏贤文; 刘少勇; 李文胜; 郭红艳; 李冬雪


    目的:研究录像脑电图对发作性疾病的临床诊断和鉴别诊断的价值。方法:对148例临床发作性症状表现患者行录像脑电图长程监测,监测时间15~20h。结果:148例患者,录像脑电图异常者127例(85.81%),均在睡眠状态下出现痫性放电,其中仅38例(25.68%)伴有清醒状态下异常。睡眠异常多出现在NREMⅠ~Ⅱ期(90.55%),REM期未见。有97例(76.38%)睡眠异常患者,痫性波夹杂在睡眠纺锤中和/或其前后爆发。结论:录像脑电图监测对发作性疾病判定是否患有癫痫的诊断中起决定性作用;清醒状态下能检出痫性放电者,睡眠时就一定能够检测出来;睡眠纺锤对痫性放电可能有诱发和强化作用。%Objective :Value of video‐electroencephalogram (VEEG) ,which is used on clinical diagnosis of epilepsy , sort and differential diagnosis .Methods :Patients of one hundred and forty‐eight who have clinic outbreak symptom were monitored with VEEG for a period ,which lasted from fifteen to twenty hours .Results:One hundred and twenty‐seven patients (rate:85 .81% ) are abnormal ,who are monitored with epilepsic EEG in sleepy time ,and thirty‐eight of it(rate:25 .68% ) are abnormal in clear‐headed time .Sleep abnormal EEG often were monitored in NREM Ⅰ ~ Ⅱ (rate:90.55% ) ,nothing is seen in REM .Ninty‐seven patients(rate :76 .38% ) whose epilesic wave break out in sleepic spin‐dle period or around it .Conclusion:VEEG have a crucial function on clinical diagnosis of epilepsy ,sort and differential diagnosis ;can check a xian to turn on electricty under the awake status ,sleep can definitely examine;Sleepic spindle pe‐riod can induce epilepsic wave and enhance it .

  9. Yeast artificial chromosome contigs reveal that distal variable-region genes reside at least 3 megabases from the joining regions in the murine immunoglobulin kappa locus. (United States)

    George, J B; Li, S; Garrard, W T


    The immunoglobulin kappa gene locus encodes 95% of the light chains of murine antibody molecules and is thought to contain up to 300 variable (V kappa)-region genes generally considered to comprise 20 families. To delineate the locus we have isolated 29 yeast artificial chromosome genomic clones that form two contigs, span > 3.5 megabases, and contain two known non-immunoglobulin kappa markers. Using PCR primers specific for 19 V kappa gene families and Southern analysis, we have refined the genetically defined order of these V kappa gene families. Of these, V kappa 2 maps at least 3.0 Mb from the joining (J kappa) region and appears to be the most distal V kappa gene segment. Images Fig. 3 Fig. 4 PMID:8618913

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

    Energy Technology Data Exchange (ETDEWEB)

    Spilsbury, Alison [Reading School of Pharmacy, University of Reading, Reading RG6 6UB (United Kingdom); Vauzour, David; Spencer, Jeremy P.E. [Molecular Nutrition Group, Centre for Integrative Neuroscience and Neurodynamics, School of Chemistry, Food and Pharmacy, University of Reading, Reading RG6 6AP (United Kingdom); Rattray, Marcus, E-mail: [Reading School of Pharmacy, University of Reading, Reading RG6 6UB (United Kingdom)


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

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

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


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

  12. Extreme value distributions

    CERN Document Server

    Ahsanullah, Mohammad


    The aim of the book is to give a through account of the basic theory of extreme value distributions. The book cover a wide range of materials available to date. The central ideas and results of extreme value distributions are presented. The book rwill be useful o applied statisticians as well statisticians interrested to work in the area of extreme value distributions.vmonograph presents the central ideas and results of extreme value distributions.The monograph gives self-contained of theory and applications of extreme value distributions.

  13. Characteristics of hepatic nuclear-transcription factor-kappa B expression and quantitative analysis in rat hepatocarcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Wei Wu; Wen-Jing Gu; Deng-Fu Yao; Li-Wei Qiu; Wen-Li Sai; Jun-Jun Shen; Hong-Bo Yu; Xin-Hua Wu; Yue-Ming Li; Yi-Lang Wang


    BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. We analyzed the expression of nuclear-transcription factor-kappa B (NF-κB) during hepatocarcinogenesis in order to evaluate its dynamic expression and its clinical value in the development and diagnosis of HCC. METHODS: Hepatoma models were induced by oral administration of 2-acetamidoflurene (2-FAA) to male Sprague-Dawley rats. Morphological changes were observed afterhematoxylinandeosinstaining.Thecellulardistribution of NF-κB expression during different stages of cancer development was investigated by immunohistochemistry, and the level of NF-κB expression in liver tissues was quantitatively analyzed by ELISA. The gene fragments of hepatic NF-κB were amplified by nested-polymerase chain reaction assay. RESULTS: Hepatocytes showed vacuole-like degeneration during the early stages, then had a hyperplastic nodal appearance during the middle stages, and finally progressed to tubercles of cancerous nests with high differentiation. The NF-κB-positive material was buff-colored, fine particles localized in the nucleus, and the incidence of NF-κB-positive cells was 81.8% in degeneration, 83.3% in precancerous lesions, and 100% in cancerous tissues. All of these values were higher than those in controls (P CONCLUSION: The NF-κB signal transduction pathway is activated during the early stages of HCC development, and its abnormal expression may be associated with the occurrence of HCC.

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

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


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

  15. Cytokine-induced proapoptotic gene expression in insulin-producing cells is related to rapid, sustained, and nonoscillatory nuclear factor-kappaB activation

    DEFF Research Database (Denmark)

    Ortis, Fernanda; Cardozo, Alessandra K; Crispim, Daisy


    Cytokines, such as IL-1beta and TNF-alpha, contribute to pancreatic beta-cell death in type 1 diabetes mellitus. The transcription factor nuclear factor-kappaB (NF-kappaB) mediates cytokine-induced beta-cell apoptosis. Paradoxically, NF-kappaB has mostly antiapoptotic effects in other cell types....

  16. Systemic inhibition of NF-kappaB activation protects from silicosis.

    Directory of Open Access Journals (Sweden)

    Michelangelo Di Giuseppe

    Full Text Available BACKGROUND: Silicosis is a complex lung disease for which no successful treatment is available and therefore lung transplantation is a potential alternative. Tumor necrosis factor alpha (TNFalpha plays a central role in the pathogenesis of silicosis. TNFalpha signaling is mediated by the transcription factor, Nuclear Factor (NF-kappaB, which regulates genes controlling several physiological processes including the innate immune responses, cell death, and inflammation. Therefore, inhibition of NF-kappaB activation represents a potential therapeutic strategy for silicosis. METHODS/FINDINGS: In the present work we evaluated the lung transplant database (May 1986-July 2007 at the University of Pittsburgh to study the efficacy of lung transplantation in patients with silicosis (n = 11. We contrasted the overall survival and rate of graft rejection in these patients to that of patients with idiopathic pulmonary fibrosis (IPF, n = 79 that was selected as a control group because survival benefit of lung transplantation has been identified for these patients. At the time of lung transplantation, we found the lungs of silica-exposed subjects to contain multiple foci of inflammatory cells and silicotic nodules with proximal TNFalpha expressing macrophage and NF-kappaB activation in epithelial cells. Patients with silicosis had poor survival (median survival 2.4 yr; confidence interval (CI: 0.16-7.88 yr compared to IPF patients (5.3 yr; CI: 2.8-15 yr; p = 0.07, and experienced early rejection of their lung grafts (0.9 yr; CI: 0.22-0.9 yr following lung transplantation (2.4 yr; CI:1.5-3.6 yr; p<0.05. Using a mouse experimental model in which the endotracheal instillation of silica reproduces the silica-induced lung injury observed in humans we found that systemic inhibition of NF-kappaB activation with a pharmacologic inhibitor (BAY 11-7085 of IkappaB alpha phosphorylation decreased silica-induced inflammation and collagen deposition. In contrast, transgenic

  17. Morin modulates the oxidative stress-induced NF-kappaB pathway through its anti-oxidant activity. (United States)

    Kim, Ji Min; Lee, Eun Kyeong; Park, Gwangli; Kim, Mi Kyung; Yokozawa, Takako; Yu, Byung Pal; Chung, Hae Young


    Morin is a flavone that has anti-inflammatory effects through a mechanism that is not well understood. Based on the extreme sensitive nature of the transcription factor, NF-kB to redox change, it is postulated that morin's anti-NF-kappaB activation likely depends on its ability to scavenge excessive reactive species [RS]. The present study assessed the extent of morin's ability to modulate RS-induced NF-kappaB activation through its scavenging activity. Results indicate that morin neutralized RS in vitro and inhibited t-BHP-induced RS generation. It also examined morin for suppressed redox-sensitive transcription factor NF-kappaB activation via reduced DNA binding activity, I kappaB alpha phosphorylation and p65/p50 nuclear translocation. The more important finding was that suppression of the NF-kappaB cascade by morin was modulated through the ERK and p38 MAPKs signal transduction pathways in endothelial cells. As a consequence, morin's anti-oxidant effect extended expression level of NF-kappaB dependent pro-inflammatory genes, thereby reducing COX-2, iNOS and 5-LOX. The data indicate that morin has strong anti-oxidative power against RS-induced NF-kappaB modulation through the ERK and p38 MAPKs signalling pathways by its RS scavenging activity. The significance of the current study is the new revelation that morin may have potential as an effective anti-inflammatory therapeutic agent.

  18. Ribosomal protein S3: a KH domain subunit in NF-kappaB complexes that mediates selective gene regulation. (United States)

    Wan, Fengyi; Anderson, D Eric; Barnitz, Robert A; Snow, Andrew; Bidere, Nicolas; Zheng, Lixin; Hegde, Vijay; Lam, Lloyd T; Staudt, Louis M; Levens, David; Deutsch, Walter A; Lenardo, Michael J


    NF-kappaB is a DNA-binding protein complex that transduces a variety of activating signals from the cytoplasm to specific sets of target genes. To understand the preferential recruitment of NF-kappaB to specific gene regulatory sites, we used NF-kappaB p65 in a tandem affinity purification and mass spectrometry proteomic screen. We identified ribosomal protein S3 (RPS3), a KH domain protein, as a non-Rel subunit of p65 homodimer and p65-p50 heterodimer DNA-binding complexes that synergistically enhances DNA binding. RPS3 knockdown impaired NF-kappaB-mediated transcription of selected p65 target genes but not nuclear shuttling or global protein translation. Rather, lymphocyte-activating stimuli caused nuclear translocation of RPS3, parallel to p65, to form part of NF-kappaB bound to specific regulatory sites in chromatin. Thus, RPS3 is an essential but previously unknown subunit of NF-kappaB involved in the regulation of key genes in rapid cellular activation responses. Our observations provide insight into how NF-kappaB selectively controls gene expression.

  19. Gnotobiotic IL-10; NF-kappaB mice develop rapid and severe colitis following Campylobacter jejuni infection.

    Directory of Open Access Journals (Sweden)

    Elisabeth Lippert

    Full Text Available Limited information is available on the molecular mechanisms associated with Campylobacter jejuni (C. jejuni induced food-borne diarrheal illnesses. In this study, we investigated the function of TLR/NF-kappaB signaling in C. jejuni induced pathogenesis using gnotobiotic IL-10(-/-; NF-kappaB(EGFP mice. In vitro analysis showed that C. jejuni induced IkappaB phosphorylation, followed by enhanced NF-kappaB transcriptional activity and increased IL-6, MIP-2alpha and NOD2 mRNA accumulation in infected-mouse colonic epithelial cells CMT93. Importantly, these events were blocked by molecular delivery of an IkappaB inhibitor (Ad5IkappaBAA. NF-kappaB signalling was also important for C.jejuni-induced cytokine gene expression in bone marrow-derived dendritic cells. Importantly, C. jejuni associated IL-10(-/-; NF-kappaB(EGFP mice developed mild (day 5 and severe (day 14 ulcerating colonic inflammation and bloody diarrhea as assessed by colonoscopy and histological analysis. Macroscopic analysis showed elevated EGFP expression indicating NF-kappaB activation throughout the colon of C. jejuni associated IL-10(-/-; NF-kappaB(EGFP mice, while fluorescence microscopy revealed EGFP positive cells to be exclusively located in lamina propria mononuclear cells. Pharmacological NF-kappaB inhibition using Bay 11-7085 did not ameliorate C. jejuni induced colonic inflammation. Our findings indicate that C. jejuni induces rapid and severe intestinal inflammation in a susceptible host that correlates with enhanced NF-kappaB activity from lamina propria immune cells.

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

    Energy Technology Data Exchange (ETDEWEB)

    Zhong, Xia, E-mail: [Department of Emergency, Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Li, Xiaonan; Liu, Fuli; Tan, Hui [Department of Emergency, Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Shang, Deya, E-mail: [Department of Emergency, Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China)


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

  1. Uncoupling of inflammation and insulin resistance by NF-kappaB in transgenic mice through elevated energy expenditure. (United States)

    Tang, Tianyi; Zhang, Jin; Yin, Jun; Staszkiewicz, Jaroslaw; Gawronska-Kozak, Barbara; Jung, Dae Young; Ko, Hwi Jin; Ong, Helena; Kim, Jason K; Mynatt, Randy; Martin, Roy J; Keenan, Michael; Gao, Zhanguo; Ye, Jianping


    To study the metabolic activity of NF-kappaB, we investigated phenotypes of two different mouse models with elevated NF-kappaB activities. The transcriptional activity of NF-kappaB is enhanced either by overexpression of NF-kappaB p65 (RelA) in aP2-p65 mice or inactivation of NF-kappaB p50 (NF-kappaB1) through gene knock-out. In these models, energy expenditure was elevated in day and night time without a change in locomotion. The mice were resistant to adulthood obesity and diet-induced obesity without reduction in food intake. The adipose tissue growth and adipogenesis were inhibited by the elevated NF-kappaB activity. Peroxisome proliferator-activator receptor gamma expression was reduced by NF-kappaB at the transcriptional level. The two models exhibited elevated inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6) in adipose tissue and serum. However, insulin sensitivity was not reduced by the inflammation in the mice on a chow diet. On a high fat diet, the mice were protected from insulin resistance. The glucose infusion rate was increased more than 30% in the hyperinsulinemic-euglycemic clamp test. Our data suggest that the transcription factor NF-kappaB promotes energy expenditure and inhibits adipose tissue growth. The two effects lead to prevention of adulthood obesity and dietary obesity. The energy expenditure may lead to disassociation of inflammation with insulin resistance. The study indicates that inflammation may prevent insulin resistance by eliminating lipid accumulation.

  2. Upregulation of the kappa opioidergic system in left ventricular rat myocardium in response to volume overload: Adaptive changes of the cardiac kappa opioid system in heart failure. (United States)

    Treskatsch, Sascha; Shaqura, Mohammed; Dehe, Lukas; Feldheiser, Aarne; Roepke, Torsten K; Shakibaei, Mehdi; Spies, Claudia D; Schäfer, Michael; Mousa, Shaaban A


    Opioids have long been known for their analgesic effects and are therefore widely used in anesthesia and intensive care medicine. However, in the last decade research has focused on the opioidergic influence on cardiovascular function. This project thus aimed to detect the precise cellular localization of kappa opioid receptors (KOR) in left ventricular cardiomyocytes and to investigate putative changes in KOR and its endogenous ligand precursor peptide prodynorphin (PDYN) in response to heart failure. After IRB approval, heart failure was induced using a modified infrarenal aortocaval fistula (ACF) in male Wistar rats. All rats of the control and ACF group were characterized by their morphometrics and hemodynamics. In addition, the existence and localization as well as adaptive changes of KOR and PDYN were investigated using radioligand binding, double immunofluorescence confocal analysis, RT-PCR and Western blot. Similar to the brain and spinal cord, [(3)H]U-69593 KOR selective binding sites were detected the left ventricle (LV). KOR colocalized with Cav1.2 of the outer plasma membrane and invaginated T-tubules and intracellular with the ryanodine receptor of the sarcoplasmatic reticulum. Interestingly, KOR could also be detected in mitochondria of rat LV cardiomyocytes. As a consequence of heart failure, KOR and PDYN were up-regulated on the mRNA and protein level in the LV. These findings suggest that the cardiac kappa opioidergic system might modulate rat cardiomyocyte function during heart failure.

  3. Disruption of B-cell homeostatic control mediated by the BLV-Tax oncoprotein: association with the upregulation of Bcl-2 and signaling through NF-kappaB. (United States)

    Szynal, Maud; Cleuter, Yvette; Beskorwayne, Terry; Bagnis, Claude; Van Lint, Carine; Kerkhofs, Pierre; Burny, Aisene; Martiat, Philippe; Griebel, Philip; Van den Broeke, Anne


    Transactivating proteins associated with complex onco-retroviruses including human T-cell leukemia virus-1 (HTLV-1) and bovine leukemia virus (BLV) mediate transformation using poorly understood mechanisms. To gain insight into the processes that govern tumor onset and progression, we have examined the impact of BLV-Tax expression on ovine B-cells, the targets of BLV in experimentally infected sheep, using B-cell clones that are dependent on CD154 and gammac-common cytokines. Tax was capable of mediating progression of B-cells from cytokine dependence to cytokine independence, indicating that the transactivator can over-ride signaling pathways typically controlled by cytokine receptor activation in B-cells. When examined in the presence of both CD154 and interleukin-4, Tax had a clear supportive role on B-cell growth, with an impact on B-cell proliferation, cell cycle phase distribution, and survival. Apoptotic B-cell death mediated by growth factor withdrawal, physical insult, and NF-kappaB inhibition was dramatically reduced in the presence of Tax. Furthermore, the expression of Tax was associated with higher Bcl-2 protein levels, providing rationale for the rescue signals mediated by the transactivator. Finally, Tax expression in B-cells led to a dramatic increase of nuclear RelB/p50 and p50/p50 NF-kappaB dimers, indicating that cellular signaling through NF-kappaB is a major contributory mechanism in the disruption of B-cell homeostasis. Although Tax is involved in aspects of pathogenesis that are unique to complex retroviruses, the viral strategies associated with this transactivating oncoprotein may have wide-ranging effects that are relevant to other B-cell malignancies.

  4. Avance en el diseño de un péptido bloqueador del receptor Opioide Kappa 2 humano

    Directory of Open Access Journals (Sweden)

    Velásquez Álvarez Alvaro Andrés


    Full Text Available

    Se evaluó la posibilidad de predecir una probable estructura secundaria para el Receptor Opioide Kappa 2 humano tomando como base la secuencia de aminoácidos del Receptor Opioide Kappa 1 humano. La estructura predicha mostró ser compatible con los datos que se poseen acerca de este tipo de receptores. Con esta prueba inicial, el proyecto que tiene como objetivo principal diseñar un análogo proteico para el Receptor Opioide Kappa 2 humano, ha mostrado el nivel mínimo de viabilidad necesario para ser continuado.


    Directory of Open Access Journals (Sweden)

    Sonia Viviana Beltrán Velásquez


    Full Text Available Se evaluó la posibilidad de predecir una probable estructura secundaria para el Receptor Opioide Kappa 2 humano tomando como base la secuencia de aminoácidos del Receptor Opioide Kappa 1 humano. La estructura predicha mostró ser compatible con los datos que se poseen acerca de este tipo de receptores. Con esta prueba inicial, el proyecto que tiene como objetivo principal el diseñar un análogo proteico para el ReceptorOpioide Kappa 2 humano, ha mostrado el nivel mínimo de viabilidad necesario para ser continuado.

  6. The complete exon-intron structure of the 156-kb human gene NFKB1, which encodes the p105 and p50 proteins of transcription factors NF-{kappa}B and I{kappa}B-{gamma}: Implications for NF-{kappa}B-mediated signal transduction

    Energy Technology Data Exchange (ETDEWEB)

    Heron, E.; Deloukas, P.; van Loon, A.P.G.M. [F. Hoffmann-La Roche Limited, Basel (Switzerland)


    The NFKB1 gene encodes three proteins of the NF-{kappa}/Rel and I{kappa}B families: p105, p50, and (in mouse) I{kappa}B-{gamma}. We determined the complete genomic structure of human NFKB1. NFKB1 spans 156 kb and has 24 exons with introns varying between 40,000 and 323 bp in length. Although NFKB2, which encodes p100 and p52, also has 24 exons and has a comparable exon-intron structure, it is 20 times shorter than NFKB1. We propose that the long size of NFKB1 is important for transient activation of NF-{kappa}B complexes containing p50. I{kappa}B-{gamma} corresponds to the carboxyl-terminal half of p105. DNA sequence analysis showed that the 3{prime}-end of human intron 11 and the 5{prime}-end of exon 12 of NFKB1 are colinear with the 5{prime}-untranslated region of mouse I{kappa}B-{gamma} cDNA. I{kappa}B-{gamma} is thus likely to be generated by transcription starting within intron 11 and not by alternative splicing of the mouse mRNA encoding p105 and p50. 71 refs., 5 figs., 1 tab.

  7. H to Zn Ionization Equilibrium for the Non-Maxwellian Electron kappa-distributions: Updated Calculations

    CERN Document Server

    Dzifcakova, Elena


    New data for calculation of the ionization and recombination rates have have been published in the past few years. Most of these are included in CHIANTI database. We used these data to calculate collisional ionization and recombination rates for the non-Maxwellian kappa-distributions with an enhanced number of particles in the high-energy tail, which have been detected in the solar transition region and the solar wind. Ionization equilibria for elements H to Zn are derived. The kappa-distributions significantly influence both the ionization and recombination rates and widen the ion abundance peaks. In comparison with Maxwellian distribution, the ion abundance peaks can also be shifted to lower or higher temperatures. The updated ionization equilibrium calculations result in large changes for several ions, notably Fe VIII--XIV. The results are supplied in electronic form compatible with the CHIANTI database.

  8. Spectral Interpretation of Radio Sounder-Stimulated Magnetospheric Plasma Resonances in Terms of Kappa Distributions (United States)

    Benson, Robert F.; Vinas, Adolfo, F.; Fainberg, Joseph; Osherovich, Vladimir A.; Purser, Carola M.; Galkin, Ivan A.; Reinisch, Bodo W.


    Magnetosphere sounders stimulate plasma resonances between the harmonics of the electron cyclotron frequency and above the upper-hybrid frequency. More than three decades ago they were recognized as equivalent to ionospheric topside-sounder-stimulated resonances, designated as Qn resonances a decade earlier, with one important difference: the magnetospheric Qn frequencies often indicated that the background electron-velocity distribution was non-Maxwellian. Interpretations based on bi-Maxwellian and kappa distributions have been proposed. Here we expand on the latter, which requires fewer free parameters, by comparing kappa-derived Qn frequencies with observations from the Radio Plasma Imager on the Imager for Magnetopause-to-Aurora Global Exploration (IMAGE) satellite.

  9. $\\kappa$-generalized models of income and wealth distributions: A survey

    CERN Document Server

    Clementi, F; Kaniadakis, G; Landini, S


    The paper provides a survey of results related to the "$\\kappa$-generalized distribution", a statistical model for the size distribution of income and wealth. Topics include, among others, discussion of basic analytical properties, interrelations with other statistical distributions as well as aspects that are of special interest in the income distribution field, such as the Gini index and the Lorenz curve. An extension of the basic model that is most able to accommodate the special features of wealth data is also reviewed. The survey of empirical applications given in this paper shows the $\\kappa$-generalized models of income and wealth to be in excellent agreement with the observed data in many cases.

  10. Resolving the electron temperature discrepancies in HII Regions and Planetary Nebulae: kappa-distributed electrons

    CERN Document Server

    Nicholls, David C; Sutherland, Ralph S


    The measurement of electron temperatures and metallicities in H ii regions and Planetary Nebulae (PNe) has-for several decades-presented a problem: results obtained using different techniques disagree. What it worse, they disagree consistently. There have been numerous attempts to explain these discrepancies, but none has provided a satisfactory solution to the problem. In this paper, we explore the possibility that electrons in H ii regions and PNe depart from a Maxwell-Boltzmann equilibrium energy distribution. We adopt a "kappa-distribution" for the electron energies. Such distributions are widely found in Solar System plasmas, where they can be directly measured. This simple assumption is able to explain the temperature and metallicity discrepancies in H ii regions and PNe arising from the different measurement techniques. We find that the energy distribution does not need to depart dramatically from an equilibrium distribution. From an examination of data from Hii regions and PNe it appears that kappa ~ ...

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

    Energy Technology Data Exchange (ETDEWEB)

    Hussain, S.; Mahmood, S.; Hafeez Ur-Rehman [Theoretical Plasma Physics Division, PINSTECH, P.O. Nilore, Islamabad 44000, Pakistan and Department of Physics and Applied Mathematics, PIEAS, P.O. Nilore, Islamabad 44000 (Pakistan)


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

  12. The Kappa in J/Psi -> Kpplus-piminus-Kminus-piplus

    CERN Document Server

    Bugg, D V


    BES II data for J/Psi->K*(890)Kpi reveal a strong kappa peak in the Kpi S-wave near threshold. Both magnitude and phase are determined in slices of Kpi mass by interferences with strong Ko(1430), K1(1270) and K1(1400) signals. The phase variation with mass agrees within errors with LASS data for Kpi elastic scattering. A combined fit is presented to both BES and LASS data. The fit uses a Breit-Wigner amplitude with an s-dependent width containing an Adler zero. The kappa pole is at 760+-20(stat)+-40(syst) - i(420+-45+-60syst) MeV. The S-wave I=0 scattering length a_0 = 0.23+-0.04 (in units of m(pi)) is close to the prediction 0.19+-0.02 of Chiral Perturbation Theory.

  13. Coherently amplified negative feedback loop as a model for NF-kappaB oscillations (United States)

    Joo, Jaewook


    The cells secrets various signaling molecules as a response to an external signal and modulate its own signaling processes. The precise role of this autocrine and/or paracrine signaling on cell information processing is mostly unknown. We will present the effect of TNF alpha autocrine signaling on NF-kappaB oscillations, using a simplified model of coherently amplified negative feedback loop. We will discuss the bifurcation diagram (i.e., dose-response curve), especially the robustness and the tenability of the period of NF-kappaB oscillations. Finally, we will compare the results from the above model with those from a previous model of time-delayed negative feedback alone.

  14. Dual kappa and lambda expressing in mature B-cell neoplasm: An unusual case

    Directory of Open Access Journals (Sweden)

    Ashish Gupta


    Full Text Available A 57 years old male presented with transfusion dependent anemia for last 2 months with mild weight loss and on and off fever. On examination he was found to have small axillary lymph nodes with moderate splenomegaly. Flow cytometry revealed 63.2% cells in the lymphocyte window in cluster of differentiation (CD 45 versus side scatter plot. Further analysis on CD-19 gated cells showed that - 75.9% of these cells expressed CD-19 plus the expression of CD23, CD25, CD43, CD20 and CD22. The entire cluster showed dual expression of kappa and lambda light chains. Final diagnosis of low-grade B non-Hodgkin lymphoma was made. Given that dual kappa and lambda expressing in mature B cell neoplasm has been described in literature, it is important to differentiate such cases from reactive lymphoid proliferations.

  15. Zinc inhibits nuclear factor-kappa B activation and sensitizes prostate cancer cells to cytotoxic agents. (United States)

    Uzzo, Robert G; Leavis, Paul; Hatch, William; Gabai, Vladimir L; Dulin, Nickolai; Zvartau, Nadezhda; Kolenko, Vladimir M


    Prostate carcinogenesis involves transformation of zinc-accumulating normal epithelial cells to malignant cells, which do not accumulate zinc. In this study, we demonstrate by immunoblotting and immunohistochemistry that physiological levels of zinc inhibit activation of nuclear factor (NF)-kappa B transcription factor in PC-3 and DU-145 human prostate cancer cells, reduce expression of NF-kappa B-controlled antiapoptotic protein c-IAP2, and activate c-Jun NH(2)-terminal kinases. Preincubation of PC-3 cells with physiological concentrations of zinc sensitized tumor cells to tumor necrosis factor (TNF)-alpha, and paclitaxel mediated cell death as defined by terminal deoxynucleotidyl transferase-mediated nick end labeling assay. These results suggest one possible mechanism for the inhibitory effect of zinc on the development and progression of prostate malignancy and might have important consequences for the prevention and treatment of prostate cancer.

  16. Ion acoustic solitons in a solar wind magnetoplasma with Kappa distributed electrons (United States)

    Devanandhan, Selvaraj; Singh, Satyavir; Singh Lakhina, Gurbax; Sreeraj, T.


    In many space plasma environments, the velocity distribution of particles often deviates from Maxwellian and is well-modelled by a kappa distribution function. We have analyzed the ion acoustic soliton in a magnetized consisting of plasma Protons, Helium ions, an electron beam and superthermal hot electrons following kappa distribution function. Under the assumption of weak nonlinearity, the ion-acoustic solitons are described by the Korteweg-de-Vries-Zakharov-Kuznetsov (KdV-ZK) equation. The solution of KdV-ZK equation is used to model the characteristics of the ion acoustic solitary waves in a solar wind magnetoplasma observed at 1 AU. We have found both slow and fast ion acoustic solitons in our study. It is found that the superthermality of hot electrons greatly influence the existence regime of the solitary waves. The numerical results of this study to explain solar wind observations will be discussed in detail.

  17. “Lagrangian Temperature”: Derivation and Physical Meaning for Systems Described by Kappa Distributions

    Directory of Open Access Journals (Sweden)

    George Livadiotis


    Full Text Available The paper studies the “Lagrangian temperature” defined through the entropy maximization in the canonical ensemble, which is the negative inverse Lagrangian multiplier corresponding to the constraint of internal energy. The Lagrangian temperature is derived for systems out of thermal equilibrium described by kappa distributions such as space plasmas. The physical meaning of temperature is manifested by the equivalency of two different definitions, that is, through Maxwell’s kinetic theory and Clausius’ thermodynamics. The equivalency of the two definitions is true either for systems at thermal equilibrium described by Maxwell distributions or for systems out of thermal equilibrium described by kappa distributions, and gives the meaning of the actual temperature, that is, the real or measured temperature. However, the third definition, that of the Lagrangian temperature, coincides with the primary two definitions only at thermal equilibrium, and thus, in the general case of systems out of thermal equilibrium, it does not represent the actual temperature, but it is rather a function of this. The paper derives and examines the exact expression and physical meaning of the Lagrangian temperature, showing that it has essentially different content to what is commonly thought. This is achieved by: (i maximizing the entropy in the continuous description of energy within the general framework of non-extensive statistical mechanics, (ii using the concept of the “N-particle” kappa distribution, which is governed by a special kappa index that is invariant of the degrees of freedom and the number of particles, and (iii determining the appropriate scales of length and speed involved in the phase-space microstates. Finally, the paper demonstrates the behavior of the Lagrangian against the actual temperature in various datasets of space plasmas.

  18. Inflammation and NF-kappa B in Alzheimer's Disease and Diabetes


    Granic, Ivica; Dolga, Amalia; Ingrid M. Nijholt; van Dijk, Gertjan; Eisel, Ulrich L.M.


    Inflammatory processes are a hallmark of many chronic diseases including Alzheimer's disease and diabetes mellitus. Fairly recent statistical evidence indicating that type 2 diabetes increases the risk of developing Alzheimer's disease has led to investigations of the potential common processes that could explain this relation. Here, we review the literature on how inflammation and the inducible nuclear factor NF-kappa B might be involved in both diabetes mellitus and Alzheimer's disease and ...

  19. Targeting the I-Kappa-B Kinase Epsilon (IKKe) for Breast Cancer Therapy (United States)


    inhibits growth and invasiveness of breast cancer cells. (under review, submitted to Breast Cancer Research) Appendix II. Bin Qin, Ravi S. Shukla , Kun...inhibitor of kappaB kinase pathways in oncogenic initiation and progression. Oncogene 2006, 25(51):6817-6830. 21. Sung B, Pandey MK , Nakajima Y, Nishida...Bin Qin, Ravi S. Shukla , Kun Cheng* Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte

  20. Nuclear Factor-kappaB controls the reaggregation of 3D neurosphere cultures in vitro

    Directory of Open Access Journals (Sweden)

    D Widera


    Full Text Available The approach of reaggregation involves the regeneration and self-renewal of histotypical 3D spheres from isolated tissue kept in suspension culture. Reaggregated spheres can be used as tumour, genetic, biohybrid and neurosphere models. In addition the functional superiority of 3D aggregates over conventional 2D cultures developed the use of neurospheres for brain engineering of CNS diseases. Thus 3D aggregate cultures created enormous interest in mechanisms that regulate the formation of multicellular aggregates in vitro. Here we analyzed mechanisms guiding the development of 3D neurosphere cultures. Adult neural stem cells can be cultured as self-adherent clusters, called neurospheres. Neurospheres are characterised as heterogeneous clusters containing unequal stem cell sub-types. Tumour necrosis factor-alpha (TNF- alpha is one of the crucial inflammatory cytokines with multiple actions on several cell types. TNF- alpha strongly activates the canonical Nuclear Factor Kappa-B (NF-kappaB pathway. In order to investigate further functions of TNF in neural stem cells (NSCs we tested the hypothesis that TNF is able to modulate the motility and/or migratory behaviour of SVZ derived adult neural stem cells. We observed a significantly faster sphere formation in TNF treated cultures than in untreated controls. The very fast aggregation of isolated NSCs (<2h is a commonly observed phenomenon, though the mechanisms of 3D neurosphere formation remain largely unclear. Here we demonstrate for the first time, increased aggregation and enhanced motility of isolated NSCs in response to the TNF-stimulus. Moreover, this phenomenon is largely dependent on activated transcription factor NF-kappaB. Both, the pharmacological blockade of NF-kappaB pathway by pyrrolidine dithiocarbamate (PDTC or Bay11-7082 and genetic blockade by expression of a transdominant-negative super-repressor IkappaB-AA1 led to decreased aggregation.

  1. Deposition of kappa and lambda light chains in amyloid filaments of dialysis-related amyloidosis. (United States)

    Brancaccio, D; Ghiggeri, G M; Braidotti, P; Garberi, A; Gallieni, M; Bellotti, V; Zoni, U; Gusmano, R; Coggi, G


    beta 2-Microglobulin (beta 2m) is considered to be the amyloidogenic precursor in dialysis-related amyloidosis, although the implication of other relevant cofactors in the pathogenesis of this disease has also been hypothesized. It is conceivable that substances found in amyloid deposits might represent something more than simple codeposition, possibly playing a pathogenic role in amyloidogenesis. Along these lines, a detailed analysis of the protein composition of amyloid fibrils purified from synovial material surgically obtained from nine patients on long-term dialysis was carried out. By the use of sodium dodecyl sulfate-polyacrylamide gel electrophoresis, several other protein components, in addition to beta 2m, were found. These were characterized by NH2 amino-terminal sequencing and immunoblotting. In fibrils obtained by water extraction, which fulfill the electron microscopy criteria of highly pure amyloid material, polyclonal kappa and lambda light chains were detected with a concentration of 15 micrograms/mL in the water extraction material; the beta 2m concentration was 200 micrograms/mL. Light microscopy immunohistochemistry was performed on samples from five patients. Amyloid deposits reacted with anti-beta 2m, and anti-light (kappa, lambda), chain antibodies. The immunoreaction of amyloid filaments to anti-beta 2m, anti-lambda, and anti-kappa light chain antibodies was also tested by electron microscopy by use of the immunogold staining procedure. Amyloid filaments were labeled by the three antibodies and showed a different intensity of immunostaining apparently related to their different aggregation pattern. These observations demonstrate that polyclonal immunoglobulin light chains (kappa and lambda) are not contaminants but, together with beta 2m, represent a major constituent of amyloid deposits in dialysis-related osteoarticular amyloidosis, thus indicating their possible role in amyloidogenesis.

  2. Sigma, Kappa and fo(980) in E791 and BES II data

    CERN Document Server

    Bugg, D V


    Both sigma and kappa are well established from E791 data on D->3pi and D->K-pi-pi$ and BES II data on J/Psi->omega-pi-pi and KKpipi. Fits to these data are accurately consistent with pi-pi and Kpi elastic scattering when one allows for the Adler zero which arises from Chiral Symmetry Breaking. The phase variation with mass is also consistent between elastic scattering and production data.

  3. Biochemical and functional interactions of a selective kappa opioid agonist with calcium

    Energy Technology Data Exchange (ETDEWEB)

    VonVoigtlander, P.F.; Ochoa, M.C.; Lewis, R.A.


    The discovery of the selective kappa opioid receptor agonist, U-50488H, has provided a tool for the study of the mechanisms and function of the kappa receptor-effector. We have investigated the interactions of this compound with calcium in several biochemical and functional studies to assess the involvement of calcium mechanisms in the kappa receptor-linked effector. In rat brain synaptosomes, U-50488H attenuated the uptake of /sup 45/Ca++ induced by K+ (40 mM) depolarization. This effect was concentration-related (U-50488H 10(-5) to 10(-7) M), was apparent in short (8-second) but not longer (1-minute) term incubations, and did not occur in the presence of a non-polarizing concentration (5.6 mM) of K+. Naloxone (10(-7) M) did not block this effect of U-50488H (10(-6) M), and higher concentrations (10(-5) M) alone blocked calcium uptake. We have found that the binding of the depolarizing amino acid analog, kainic acid, is enhanced by CaCl2. U-50488H (10(-4) to 10(-6) M) blocks this enhancement of /sup 3/H-kainic acid binding in vitro and also blocks the in vivo effects of kainic acid. In mice, intravenous injection of kainic acid causes scratching, convulsions, and death, depending on the dose administered. U-50488H blocks all of these effects (ED50 = 4.5 mg/kg for antagonism of convulsions induced by 27.5 mg/kg kainic acid). The convulsions induced by intracerebroventricularly administered kainic acid are also blocked by U-50488H as are those induced by similarly administered Bay K 8644, a calcium channel activator. All of these anticonvulsant effects of U-50488H were antagonized by naltrexone. Together these data indicate that the kappa agonist U-50488H has functionally relevant interactions with depolarization-related Ca++ mechanisms in the central nervous system.

  4. Studies Toward the Pharmacophore of Salvinorin A, a Potent Kappa Opioid Receptor Agonist


    Munro, Thomas A.; Mark A. Rizzacasa; Roth, Bryan L.; Toth, Beth A.; Yan, Feng


    Salvinorin A (1), from the sage Salvia divinorum, is a potent and selective kappa opioid receptor (KOR) agonist. We screened other salvinorins and derivatives for binding affinity and functional activity at opioid receptors. Our results suggest that the methyl ester and furan ring are required for activity, but that the lactone and ketone functionalities are not. Other salvinorins showed negligible binding affinity at the KOR. None of the compounds bound to mu or delta opioid receptors.

  5. Studies toward the pharmacophore of salvinorin A, a potent kappa opioid receptor agonist. (United States)

    Munro, Thomas A; Rizzacasa, Mark A; Roth, Bryan L; Toth, Beth A; Yan, Feng


    Salvinorin A (1), from the sage Salvia divinorum, is a potent and selective kappa opioid receptor (KOR) agonist. We screened other salvinorins and derivatives for binding affinity and functional activity at opioid receptors. Our results suggest that the methyl ester and furan ring are required for activity but that the lactone and ketone functionalities are not. Other salvinorins showed negligible binding affinity at the KOR. None of the compounds bound to mu or delta opioid receptors.

  6. Effects of radiation on tumor hemodynamics and NF-kappaB in breast tumors (United States)

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


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

  7. The value of value congruence. (United States)

    Edwards, Jeffrey R; Cable, Daniel M


    Research on value congruence has attempted to explain why value congruence leads to positive outcomes, but few of these explanations have been tested empirically. In this article, the authors develop and test a theoretical model that integrates 4 key explanations of value congruence effects, which are framed in terms of communication, predictability, interpersonal attraction, and trust. These constructs are used to explain the process by which value congruence relates to job satisfaction, organizational identification, and intent to stay in the organization, after taking psychological need fulfillment into account. Data from a heterogeneous sample of employees from 4 organizations indicate that the relationships that link individual and organizational values to outcomes are explained primarily by the trust that employees place in the organization and its members, followed by communication, and, to a lesser extent, interpersonal attraction. Polynomial regression analyses reveal that the relationships emanating from individual and organizational values often deviated from the idealized value congruence relationship that underlies previous theory and research. The authors' results also show that individual and organizational values exhibited small but significant relationships with job satisfaction and organizational identification that bypassed the mediators in their model, indicating that additional explanations of value congruence effects should be pursued in future research. (c) 2009 APA, all rights reserved.

  8. Inter-Coder Agreement in One-to-Many Classification: Fuzzy Kappa. (United States)

    Kirilenko, Andrei P; Stepchenkova, Svetlana


    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.

  9. NF-κB和胃癌%Nuclear Factor-kappaB Activity in Gastric Cancer

    Institute of Scientific and Technical Information of China (English)



    The nuclear factor-kappaB (NF-kB) pathway is one of the most important cellular signal trans-duction pathways involved in both physiologic processes and disease conditions. The aberrant regulation of NF-kB results in the development and progression of gastric cancer,as well as in metastasis,its treatment and chemoprevention. Therefore,targeting of NF-kappaB signaling pathway could be a potent strategy for the prevention and treatment of gastric cancers.%核因子-κB(Nuclear Factor-kappaB,NF-κB)通路是机体最重要的细胞内信号传导通路之一.NF-κB失调涉及胃癌的发生发展、浸润转移、治疗和化学预防等方面.靶向NF-κB信号通路可能是胃癌治疗和预防的一个有效策略.

  10. In silico simulation of inhibitor drug effects on nuclear factor-kappaB pathway dynamics. (United States)

    Sung, Myong-Hee; Simon, Richard


    NF-kappaB is a transcription factor family that activates numerous genes that are related to cell survival, apoptosis, and cell migration. Its persistent activity is associated with tumor formation, growth, metastasis, and drug resistance in many cancer types, including lymphoma, colon cancer, and breast cancer. Current therapeutic efforts for inhibiting this central "switch" include using small molecules to block a selected target in this pathway. Recognizing the regulatory network structure of the NF-kappaB pathway, we examine in silico the effects of inhibitors targeting various network components, using a kinetic model of the pathway. By simulating the corresponding perturbed system dynamics, we show the resulting time course of inhibition has distinct target-specific profiles. In particular, greater oscillatory potential exists for inhibition of upstream events than for direct inhibition of NF-kappaB, at low drug concentrations. This phenomenon is observed also when we examine the dynamic effects of the recently approved proteasome inhibitor, bortezomib (PS-341), and compare it with other inhibitors, taking its pharmacokinetics into consideration. Such kinetic analyses of the "drugged" molecular system will facilitate optimal drug target selection and the development of treatment protocols for a molecularly targeted therapy.

  11. Role of Nuclear Factor kappaB in Intestine Injury Induced by Hepatic Ischemia Reperfusion

    Institute of Scientific and Technical Information of China (English)

    陈俊华; 王国斌


    Summary: The role of nuclear factor kappaB in intestine injury induced by hepatic ischemia reperfusion was investigated. Eighteen male Wistar rats were divided into 3 groups randomly: sham operation group (group A), hepatic ischemia reperfusion group (group B) and hepatic ischemia reperfusion plus pyrrolidine dithiocarbamate (PDTC) group (group C). The rats in group A were only subjected to laparotomy, those in group B underwent partial hepatic ischemia reperfusion (ischemia for 1 h and reperfusion for 2 h) and those in group C underwent the same procedure as that of group B but received PDTC 200 mg/kg i.v. before and after ischemia. After reperfusion, tissues of jejunum and venous blood were obtained for measurement of TNF-α, MDA and MPO. The levels of TNF-α in jejunum and venous blood, the levels of MPO in jejunum in group B were significantly higher than those in group A and group C (P<0.05). There was no significant different in the levels of MDA between group B and group C. The severity of histological intestinal injury in group B and group C was similar. Hepatic ischemia reperfusion caused intestine injury, NF-kappaB may play an important role in this course and the targeting of upstream components of the inflammatory response, such as NF-kappaB, may have important therapeutic applications.

  12. The impact of kappa number composition on eucalyptus kraft pulp bleachability

    Directory of Open Access Journals (Sweden)

    M. M. Costa


    Full Text Available Consumption of chemicals during ECF bleaching of kraft pulp correlates reasonably well with kappa number, which measures with KMnO4 the total amount of oxidizable material in the pulp. However, the method does not distinguish between the oxidizable material in residual lignin and other structures susceptible to oxidation, such as hexenuronic acids (HexAs, extractives and carbonyl groups in the pulp. In this study an attempt is made to separate the main contributors to the kappa number in oxygen - delignified eucalyptus Kraft pulps and evaluate how these fractions behave during ECF bleaching using chlorine dioxide as the sole oxidant (DEDD sequence. Residual lignin and HexAs proved to be the main fractions contributing to the kappa number and chlorine dioxide consumption in ECF bleaching. Pulp bleachability with chlorine dioxide increases with increasing HexAs content of the pulp but chlorine dioxide per se does not react with HexAs. Reduction of pulp with sodium borohydride under conditions for removing carbonyl groups has no impact on bleachability. No correlation was found between the pulp of the extractive content and pulp bleachability. The removal of HexAs prior to ECF bleaching significantly decreases the formation of chlorinated organics in the pulp (OX and filtrates (AOX as well as of oxalic acids in the filtrates.

  13. Malt1 ubiquitination triggers NF-kappaB signaling upon T-cell activation. (United States)

    Oeckinghaus, Andrea; Wegener, Elmar; Welteke, Verena; Ferch, Uta; Arslan, Seda Cöl; Ruland, Jürgen; Scheidereit, Claus; Krappmann, Daniel


    Triggering of antigen receptors on lymphocytes is critical for initiating adaptive immune response against pathogens. T-cell receptor (TCR) engagement induces the formation of the Carma1-Bcl10-Malt1 (CBM) complex that is essential for activation of the IkappaB kinase (IKK)/NF-kappaB pathway. However, the molecular mechanisms that link CBM complex formation to IKK activation remain unclear. Here we report that Malt1 is polyubiquitinated upon T-cell activation. Ubiquitin chains on Malt1 provide a docking surface for the recruitment of the IKK regulatory subunit NEMO/IKKgamma. TRAF6 associates with Malt1 in response to T-cell activation and can function as an E3 ligase for Malt1 in vitro and in vivo, mediating lysine 63-linked ubiquitination of Malt1. Multiple lysine residues in the C-terminus of Malt1 serve as acceptor sites for the assembly of polyubiquitin chains. Malt1 mutants that lack C-terminal ubiquitin acceptor lysines are impaired in rescuing NF-kappaB signaling and IL-2 production in Malt1-/- T cells. Thus, our data demonstrate that induced Malt1 ubiquitination is critical for the engagement of CBM and IKK complexes, thereby directing TCR signals to the canonical NF-kappaB pathway.

  14. Pertinence of kappa and lambda recombinant antibodies directed against thyroid peroxidase in thyroid autoimmune disease. (United States)

    Bresson, D; Chardès, T; Chapal, N; Bès, C; Cerutti, M; Devauchelle, G; Bouanani, M; Mani, J C; Péraldi-Roux, S


    Forty-one single-chain variable region fragments (scFvs) directed against thyroid peroxidase (TPO) were obtained by phage display libraries constructed from thyroid-infiltrating B cells of Graves' disease patients. Among these scFvs, 24.4% used a Vkappa light chain whereas 75.6% shows a light chain of Vlamda origin. Study of light chain gene usage in the TPO antibody repertoire demonstrated a dominance of the Vkappa 1-39 and Vlambda 1-51 genes. Thyroid peroxidase probing of overlapping peptides covering the amino acid sequences of anti-TPO T2/kappa and T13/lambda variable regions demonstrated a more restricted antigen recognition on T13/lambda than on T2/kappa. These two recombinant antibodies, expressed as whole IgG1 in the baculovirus/insect cell system, inhibited the binding to TPO of serum TPO autoantibodies whatever the light chain. Our study indicates that lambda as well as kappa light chain usage are found in the TPO antibody repertoire of thyroid-infiltrating B cells and are pertinent in the pathogenesis of autoimmune thyroid disease.

  15. Characterization of the gaseous companion {\\kappa} Andromedae b: New Keck and LBTI high-contrast observations

    CERN Document Server

    Bonnefoy, M; Marleau, G -D; Schlieder, J E; Wisniewski, J; Carson, J; Covey, K R; Henning, T; Biller, B; Hinz, P; Klahr, H; Boyer, A N Marsh; Zimmerman, N; Janson, M; McElwain, M; Mordasini, C; Skemer, A; Bailey, V; Defrère, D; Thalmann, C; Skrutskie, M; Allard, F; Homeier, D; Tamura, M; Feldt, M; Cumming, A; Grady, C; Brandner, W; Kandori, R; Kuzuhara, M; Fukagawa, M; Kwon, J; Kudo, T; Hashimoto, J; Kusakabe, N; Abe, L; Brandt, T; Egner, S; Guyon, O; Hayano, Y; Hayashi, M; Hayashi, S; Hodapp, K; Ishii, M; Iye, M; Knapp, G; Matsuo, T; Mede, K; Miyama, M; Morino, J -I; Moro-Martin, A; Nishimura, T; Pyo, T; Serabyn, E; Suenaga, T; Suto, H; Suzuki, R; Takahashi,; Takami, M; Takato, N; Terada, H; Tomono, D; Turner, E; Watanabe, M; Yamada, T; Takami, H; Usuda, T


    We previously reported the direct detection of a low mass companion at a projected separation of 55+-2 AU around the B9 type star {\\kappa} Andromedae. The properties of the system (mass ratio, separation) make it a benchmark for the understanding of the formation and evolution of gas giant planets and brown dwarfs on wide-orbits. We present new angular differential imaging (ADI) images of the Kappa Andromedae system at 2.146 (Ks), 3.776 (L'), 4.052 (NB 4.05) and 4.78 {\\mu}m (M') obtained with Keck/NIRC2 and LBTI/LMIRCam, as well as more accurate near-infrared photometry of the star with the MIMIR instrument. We derive a more accurate J = 15.86 +- 0.21, H = 14.95 +- 0.13, Ks = 14.32 +- 0.09 mag for {\\kappa} And b. We redetect the companion in all our high contrast observations. We confirm previous contrasts obtained at Ks and L' band. We derive NB 4.05 = 13.0 +- 0.2 and M' = 13.3 +- 0.3 mag and estimate Log10(L/Lsun) = -3.76 +- 0.06. We build the 1-5 microns spectral energy distribution of the companion and co...

  16. Value Representations

    DEFF Research Database (Denmark)

    Rasmussen, Majken Kirkegaard; Petersen, Marianne Graves


    Stereotypic presumptions about gender affect the design process, both in relation to how users are understood and how products are designed. As a way to decrease the influence of stereotypic presumptions in design process, we propose not to disregard the aspect of gender in the design process......, as the perspective brings valuable insights on different approaches to technology, but instead to view gender through a value lens. Contributing to this perspective, we have developed Value Representations as a design-oriented instrument for staging a reflective dialogue with users. Value Representations...

  17. NF-kappaB signaling mediates vascular smooth muscle endothelin type B receptor expression in resistance arteries

    DEFF Research Database (Denmark)

    Zheng, Jian-Pu; Zhang, Yaping; Edvinsson, Lars


    Vascular smooth muscle cells (SMC) endothelin type B (ET(B)) receptor upregulation results in strong vasoconstriction and reduction of local blood flow. We hypothesizes that the underlying molecular mechanisms involve transcriptional factor nuclear factor-kappaB (NF-kappaB) pathway. ET(B) receptor...... upregulation and activation of NF-kappaB were studied at functional contraction (in vitro myograph), mRNA (real-time PCR), and protein (Western blot and immunocytochemistry) levels during organ culture of rat mesenteric arteries. Organ culture of the artery segments induced a time-dependent strong contractile...... response to sarafotoxin 6c in parallel with enhanced expression of ET(B) receptor mRNA and protein in the SMC. Western blot experiments demonstrated that phosphorylation of NF-kappaB p65 was time-dependently induced during organ culture starting at 1h. In addition, cytoplasmic IkB degradation occurred...

  18. Nuclear Translocation of Nuclear Factor Kappa B in First Trimester Deciduas and Chorionic Villi in Early Spontaneous Miscarriage Women

    Directory of Open Access Journals (Sweden)

    Chun-fang Yan


    Full Text Available The nuclear factor kappa B is widely expressed in the distinct subpopulations of chorionic villi and deciduas of first-trimester pregnancies. We examined the cellular distribution and expression of nuclear factor kappa B in the human first-trimester chorionic villi and deciduas of women with early spontaneous miscarriage and viable pregnancy by confocal laser scanning microscope and immunohistochemistry. There is a greater nuclear translocation of nuclear factor kappa B is restricted to villous stromal cells, decidual stromal cells, glandular epithelial cells and vessel endothelial cells in early spontaneous miscarriage than in viable pregnancies. Collectively these observations suggest that over-activation of nuclear factor kappa B has a relationship with early spontaneous miscarriages.

  19. Expression of a truncated receptor protein tyrosine phosphatase kappa in the brain of an adult transgenic mouse

    DEFF Research Database (Denmark)

    Shen, P; Canoll, P D; Sap, J


    Receptor protein tyrosine phosphatases (RPTPs) comprise a family of proteins that feature intracellular phosphatase domains and an ectodomain with putative ligand-binding motifs. Several RPTPs are expressed in the brain, including RPTP-kappa which participates in homophilic cell-cell interactions...... in vitro [Y.-P. Jiang, H. Wang, P. D'Eustachio, J.M. Musacchio, J. Schlessinger, J. Sap, Cloning and characterization of R-PTP-kappa, a new member of the receptor protein tyrosine phosphatase family with a proteolytically cleaved cellular adhesion molecule-like extracellular region, Mol. Cell. Biol. 13...... processes such as axonal growth and target recognition, as has been demonstrated for certain Drosophila RPTPs. The brain distribution of RPTP-kappa-expressing cells has not been determined, however. In a gene-trap mouse model with a beta-gal+neo (beta-geo) insertion in the endogenous RPTP-kappa gene...

  20. The 33rd Annual Phi Delta Kappa/Gallup Poll of the Public's Attitudes Toward the Public Schools. (United States)

    Rose, Lowell C.; Gallup, Alec M.


    Presents results of the 33rd Annual Phi Delta Kappa/Gallup Poll on the public's attitudes toward the public schools. Includes a summary of key findings and tables showing percentage distributions of responses to each question. (PKP)

  1. A20 is a negative regulator of BCL10- and CARMA3-mediated activation of NF-kappaB. (United States)

    Stilo, Romania; Varricchio, Ettore; Liguoro, Domenico; Leonardi, Antonio; Vito, Pasquale


    The molecular complex containing CARMA proteins, BCL10 and TRAF6 has been identified recently as a key component in the signal transduction pathways that regulate activation of the nuclear factor kappaB (NF-kappaB) transcription factor. Here, we report that the inducible protein A20 negatively regulates these signaling cascades by means of its deubiquitylation activity. We show that A20 perturbs assembly of the complex containing CARMA3, BCL10 and IKKgamma/NEMO, thereby suppressing activation of NF-kappaB. Together, our results further define the molecular mechanisms that control activation of NF-kappaB and reveal a function for A20 in the regulation of CARMA and BCL10 activity in lymphoid and non-lymphoid cells.

  2. Effects of ketamine on proinflammatory cytokines and nuclear factor kappaB in polyrnicrobial sepsis rats

    Institute of Scientific and Technical Information of China (English)

    Xue-Min Song; Jian-Guo Li; Yan-Lin Wang; Qing Zhou; Zhao-Hui Du; Bao-Hui Jia; Jian-Juan Ke


    AIM: To explore the effects of ketamine on hemodynamics, plasma proinflammatory cytokine (TNF-α and IL-6) levels and nuclear factor kappa B (NF-κB) activation during polymicrobial sepsis.METHODS: Male Sprague-Dawlay rats were subjected to cecal ligation and puncture (CLP) or sham operation.The rats were randomly assigned into four equal groups:sham CLP group, CLP group, ketamine (KT)I groupand KTⅡ group. Thirty minutes before CLP, ketamine (5my/kg per hour and 10 my/kg per hour, respectively) was infused continuously through the left femoral vein cannula in KT I group or KTⅡgroup. Sham CLP group and CLP group received 0.9% saline only (5 mL/kg per hour). The right femoral artery was cannulated to monitor mean arterial pressure (MAP) and heart rates (HR),and draw blood samples. The proinflammatory cytokine (TNF-α and IL-6) levels of plasma were measured using enzyme-linked immunosorbent assays (ELISA). The hepatic NF-κB activation was determined by Western blot and HPIAS 2000 image analysis system.Twenty hours after CLP, the rats were killed by right femoral artery phlebotomization.RESULTS: CLP produced progressive hypotension,and a first increase followed by a decrease in HR. The hypotension was prevented, and the HR was slightly steady in ketamine treated rats. TNF-α levels of plasma reached a peak value at 2 h after CLP. Ketamine (KT I group or KTⅡgroup) caused a significant decrease compared with CLP group at 2, 5 and 9 h time points after CLP (14.3 ± 1.9 vs 4.3 ± 0.9, 9.7 ± 1.4 vs 4.3 ±0.9; 9.3 ± 1.5 vs 4.3 ± 0.9, 8.7 ± 1.4 vs 4.3 ± 0.9; 6.0± 1.5 vs 5.0 ± 1.7, 5.3 ± 0.8 vs 5.0 ± 1.7; P < 0.01,respectively). The IL-6 levels of plasma firstly ascended and then descended in CLP group, and reached a peak value at 9 h after CLP. Ketamine (KT I group or KTⅡ group) caused a significant decrease compared with CLP group at 5, 9 or 20 h after CLP (135.0 ± 52.6 vs 60.0± 16.3, 112.5 ± 52.6 vs 60.0 ± 16.3; 410.0 ± 68.7 vs62.5 ± 12.5, 250.0

  3. [{sup 11}C]-MeJDTic: a novel radioligand for {kappa}-opioid receptor positron emission tomography imaging

    Energy Technology Data Exchange (ETDEWEB)

    Poisnel, Geraldine; Oueslati, Farhana; Dhilly, Martine; Delamare, Jerome [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France); Perrio, Cecile [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France)], E-mail:; Debruyne, Daniele [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France)], E-mail:; Barre, Louisa [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France)


    Introduction: Radiopharmaceuticals that can bind selectively the {kappa}-opioid receptor may present opportunities for staging clinical brain disorders and evaluating the efficiency of new therapies related to stroke, neurodegenerative diseases or opiate addiction. The N-methylated derivative of JDTic (named MeJDTic), which has been recently described as a potent and selective antagonist of {kappa}-opioid receptor in vitro, was labeled with carbon-11 and evaluated for in vivo imaging the {kappa}-opioid receptor in mice. Methods: [{sup 11}C]-MeJDTic was prepared by methylation of JDTic with [{sup 11}C]-methyl triflate. The binding of [{sup 11}C]-MeJDTic to {kappa}-opioid receptor was investigated ex vivo by biodistribution and competition studies using nonfasted male CD1 mice. Results: [{sup 11}C]-MeJDTic exhibited a high and rapid distribution in peripheral organs. The uptake was maximal in lung where the {kappa} receptor is largely expressed. [{sup 11}C]-MeJDTic rapidly crossed the blood-brain barrier and accumulated in the brain regions of interest (hypothalamus). The parent ligand remained the major radioactive compound in brain during the experiment. Chase studies with U50,488 (a {kappa} referring agonist), morphine (a {mu} agonist) and naltrindole (a {delta} antagonist) demonstrated that this uptake was the result of specific binding to the {kappa}-opioid receptor. Conclusion: These findings suggested that [{sup 11}C]-MeJDTic appeared to be a promising selective 'lead' radioligand for {kappa}-opioid receptor PET imaging.

  4. Persistent activation of NF-kappaB related to IkappaB's degradation profiles during early chemical hepatocarcinogenesis

    Directory of Open Access Journals (Sweden)

    García-Román Rebeca


    Full Text Available Abstract Background To define the NF-kappaB activation in early stages of hepatocarcinogenesis and its IkappaB's degradation profiles in comparison to sole liver regeneration. Methods Western-blot and EMSA analyses were performed for the NF-kappaB activation. The transcriptional activity of NF-kappaB was determined by RT-PCR of the IkappaB-α mRNA. The IkappaB's degradation proteins were determined by Western-blot assay. Results We demonstrated the persistent activation of NF-kappaB during early stages of hepatocarcinogenesis, which reached maximal level 30 min after partial hepatectomy. The DNA binding and transcriptional activity of NF-kappaB, were sustained during early steps of hepatocarcinogenesis in comparison to only partial hepatectomy, which displayed a transitory NF-kappaB activation. In early stages of hepatocarconogenesis, the IkappaB-α degradation turned out to be acute and transitory, but the low levels of IkappaB-β persisted even 15 days after partial hepatectomy. Interestingly, IkappaB-β degradation is not induced after sole partial hepatectomy. Conclusion We propose that during liver regeneration, the transitory stimulation of the transcription factor response, assures blockade of NF-kappaB until recovery of the total mass of the liver and the persistent NF-kappaB activation in early hepatocarcinogenesis may be due to IkappaB-β and IkappaB-α degradation, mainly IkappaB-β degradation, which contributes to gene transcription related to proliferation required for neoplasic progression.

  5. Ion-Cyclotron Instability in Current-Carrying Lorentzian (Kappa) and Maxwellian Plasmas with Anisotropic Temperatures: A Comparative Study (United States)


    in the solar wind and in many space plasmas often exhibit non - Maxwellian suprathermal tails that decrease as a power-law of the velocity.1 Such...AFRL-RV-PS- AFRL-RV-PS- TR-2011-0164 TR-2011-0164 ION-CYCLOTRON INSTABILITY IN CURRENT- CARRYING LORENTZIAN (KAPPA) AND MAXWELLIAN PLASMAS...1 Oct 2007 – 9 Sep 2011 4. TITLE AND SUBTITLE Ion-Cyclotron Instability in Current-Carrying Lorentzian (Kappa) and Maxwellian Plasmas 5a. CONTRACT

  6. Chemoprotective effect of a nuclear factor-kappaB inhibitor, pyrrolidine dithiocarbamate, against cisplatin-induced testicular damage in rats. (United States)

    Ilbey, Yusuf Ozlem; Ozbek, Emin; Simsek, Abdulmuttalip; Cekmen, Mustafa; Otunctemur, Alper; Somay, Adnan


    The objective of this study was to evaluate inducible nitric oxide synthase (iNOS) and nuclear factor-kappaB inhibitor (NF-kappaB) expression and the potential chemoprotective effects of an NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC), against cisplatin-induced testicular damage in rats. Rats were divided into 4 equal groups: group 1, control; group 2, injected with cisplatin (CIS) for 5 days (7 mg/kg/day intraperitoneally [IP]); group 3, injected with PDTC alone; group 4, injected with CIS plus PDTC (100 mg/kg IP). Body and testicular weights, plasma testosterone levels, and histopathologic structure of the testicular tissue were determined. The iNOS and NF-kappaB activity were evaluated immunohistochemically by staining p65 to define NF-kappaB activity. Malondialdehyde (MDA), reduced glutathione (GSH), and nitric oxide (NO) levels and glutathione peroxidase (GSH-Px) activity were assessed in testicular tissue. Body and testicular weights, plasma testosterone levels, activity of GSH-Px, and GSH levels were all significantly decreased, whereas the levels of MDA and NO were significantly increased in rats of the CIS group. PDTC treatment increased plasma testosterone levels. A significant increase in GSH levels and GSH-Px activity and a decrease in MDA and NO levels in testicular tissue were observed in the CIS + PDTC group. Immunohistochemically, there was a marked staining for iNOS and NF-kappaB/p65 expression in rats injected with CIS compared with the control (P < .001). CIS caused irregular seminiferous tubules, reduction of seminiferous epithelial layers, significant arrest of maturation, and perivascular fibrosis. Moreover, PDTC administration to CIS-treated rats significantly prevented these histopathologic chances, as well. CIS induces iNOS expression through activation of NF-kappaB/p65, and CIS-induced testicular toxicity may be prevented by PDTC, which is a selective NF-kappaB inhibitor.

  7. NF-kappaB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1alpha. (United States)

    Rius, Jordi; Guma, Monica; Schachtrup, Christian; Akassoglou, Katerina; Zinkernagel, Annelies S; Nizet, Victor; Johnson, Randall S; Haddad, Gabriel G; Karin, Michael


    The hypoxic response is an ancient stress response triggered by low ambient oxygen (O2) (ref. 1) and controlled by hypoxia-inducible transcription factor-1 (HIF-1), whose alpha subunit is rapidly degraded under normoxia but stabilized when O2-dependent prolyl hydroxylases (PHDs) that target its O2-dependent degradation domain are inhibited. Thus, the amount of HIF-1alpha, which controls genes involved in energy metabolism and angiogenesis, is regulated post-translationally. Another ancient stress response is the innate immune response, regulated by several transcription factors, among which NF-kappaB plays a central role. NF-kappaB activation is controlled by IkappaB kinases (IKK), mainly IKK-beta, needed for phosphorylation-induced degradation of IkappaB inhibitors in response to infection and inflammation. IKK-beta is modestly activated in hypoxic cell cultures when PHDs that attenuate its activation are inhibited. However, defining the relationship between NF-kappaB and HIF-1alpha has proven elusive. Using in vitro systems, it was reported that HIF-1alpha activates NF-kappaB, that NF-kappaB controls HIF-1alpha transcription and that HIF-1alpha activation may be concurrent with inhibition of NF-kappaB. Here we show, with the use of mice lacking IKK-beta in different cell types, that NF-kappaB is a critical transcriptional activator of HIF-1alpha and that basal NF-kappaB activity is required for HIF-1alpha protein accumulation under hypoxia in cultured cells and in the liver and brain of hypoxic animals. IKK-beta deficiency results in defective induction of HIF-1alpha target genes including vascular endothelial growth factor. IKK-beta is also essential for HIF-1alpha accumulation in macrophages experiencing a bacterial infection. Hence, IKK-beta is an important physiological contributor to the hypoxic response, linking it to innate immunity and inflammation.

  8. Curcumin Based Drug Screening for Inhibitors of NF kappa B in a Cell Model of Prostate Cancer Progression (United States)


    nuclear transcription factor NF kappa B; (ii) cell proliferation, (iii) anchorage independent growth, (iv) the expression of Interleukin-6, and (v) the...Inhibition of the Pro-Survival Nuclear Factor Kappa B Transcription Factor”. • Poster Presentation (Fajardo et al; as above) at the Next Generation...the pharmacokinetics of curcumin in animals and human volunteers. Planta Med 1998; 64, 353–6. 8. Hsu CH, Cheng AL. Clinical studies with curcumin

  9. Exploring the doping dependence of the Mott transition on X-ray irradiated crystals of {kappa}-(ET){sub 2}Cu[N(CN){sub 2}]Cl

    Energy Technology Data Exchange (ETDEWEB)

    Koehler, Sebastian; Tutsch, Ulrich; Naji, Ammar; Lang, Michael [Physikalisches Institut, Goethe-Universitaet Frankfurt (Germany); Sasaki, Takahiko [Institute for Materials Research, Tohoku University, Aoba-ku, Sendai, Miyagi (Japan)


    The quasi two-dimensional organic charge-transfer salt {kappa}-(ET){sub 2}Cu[N(CN){sub 2}]Cl exhibits a rich pressure vs. temperature phase diagram, including Mott-insulating and metallic phases separated by a first order transition line. By applying moderate pressures of {proportional_to}30 MPa (300 bar), the ratio of the kinetic energy to the onsite Coulomb repulsion t/U can be changed sufficiently to cross this phase transition line. Our objective is to study the effect of carrier doping and the accompanying changes of the first-order transition line and its second-order critical endpoint. We used X-ray irradiation to introduce charge carriers into the material, doping it away from half filling. We present resistivity data for the temperature range 5 Kkappa}-(ET){sub 2}Cu[N(CN){sub 2}]Cl crystals at various doping levels and discuss the accompanied changes in the p-T-phase diagram.

  10. Exploring the doping dependence of the Mott transition on X-ray irradiated crystals of {kappa}-(ET){sub 2}Cu[N(CN){sub 2}]Cl

    Energy Technology Data Exchange (ETDEWEB)

    Tutsch, Ulrich; Naji, Ammar; Lang, Michael [Physikalisches Institut, Goethe-Universitaet Frankfurt (M), SFB/TRR49, D-60438 Frankfurt (Germany); Sasaki, Takahiko [Institute for Materials Research, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai, Miyagi 980-8577 (Japan)


    The quasi two-dimensional organic charge-transfer salt {kappa}-(ET){sub 2}Cu[N(CN){sub 2}]Cl has a Mott-insulating ground state at ambient pressure, which can be transformed into a superconducting ground state (T{sub c}{approx}13 K) by applying moderate pressures of {proportional_to}30 MPa (300 bar). Our objective is to study how the first-order Mott-transition line and its second-order critical end point change on doping the material away from half filling. We use X-ray irradiation in order to introduce charge carriers in this material and take the shifts in the room-temperature resistivity as a measure of the amount of doping. We will present resistivity data for the temperature range 5 K {<=}T{<=}60 K and for pressures up to 50 MPa for a {kappa}-(ET){sub 2}Cu[N(CN){sub 2}]Cl crystal at various doping levels and discuss the accompanied changes in the p-T-phase diagram.

  11. Inhibitory effects of black pepper (Piper nigrum) extracts and compounds on human tumor cell proliferation, cyclooxygenase enzymes, lipid peroxidation and nuclear transcription factor-kappa-B. (United States)

    Liu, Yunbao; Yadev, Vivek R; Aggarwal, Bharat B; Nair, Muraleedharan G


    Black pepper (Piper nigrum) and hot pepper (Capsicum spp.) are widely used in traditional medicines. Although hot Capsicum spp. extracts and its active principles, capsaicinoids, have been linked with anticancer and anti-inflammatory activities, whether black pepper and its active principle exhibit similar activities is not known. In this study, we have evaluated the antioxidant, anti-inflammatory and anticancer activities of extracts and compounds from black pepper by using proinflammatory transcription factor NF-kappaB, COX-1 and -2 enzymes, human tumor cell proliferation and lipid peroxidation (LPO). The capsaicinoids, the alkylamides, isolated from the hot pepper Scotch Bonnet were also used to compare the bioactivities of alkylamides and piperine from black pepper. All compounds derived from black pepper suppressed TNF-induced NF-kappaB activation, but alkyl amides, compound 4 from black pepper and 5 from hot pepper, were most effective. The human cancer cell proliferation inhibitory activities of piperine and alklyl amides in Capsicum and black pepper were dose dependant. The inhibitory concentrations 50% (IC50) of the alklylamides were in the range 13-200 microg/mL. The extracts of black pepper at 200 microg/mL and its compounds at 25 microg/mL inhibited LPO by 45-85%, COX enzymes by 31-80% and cancer cells proliferation by 3.5-86.8%. Overall, these results suggest that black pepper and its constituents like hot pepper, exhibit anti-inflammatory, antioxidant and anticancer activities.

  12. Koefesien Kappa sebagai Indeks Kesepakatan Hasil Diognosis Mikroskopis Malaria di Kabupaten Belu Nusa Tenggara Timur

    Directory of Open Access Journals (Sweden)

    Fridolina Mau


    Full Text Available AbstractBlood slide examination is used as standard malaria diagnosis in Indonesia. Quality assurance for malaria microscopic examination is an important issue in the monitoring and supervision of the administration of antimalarials drugs. This step was done to determine the accuracy of thediagnosis, thus could be used for further evaluation in improving the skills of microscopic health centre personnel. This study aims to determine the accuracy of malaria microscopic examination at Primary health centre and District Health Office personnels in Belu District, Nusa Tenggara Timur.The study was an observational research with cross sectional approach. The competency of primary health center and district healt office microscopist in examining malaria blood smears were evaluated using standard blood smears compared with smears from Passive Case Detection (PCD activities. Performance in preparing blood smear were evaluatied by observation and filling the checklist. The study was conducted in April - Juni 2012 in Belu District, NTT. Quality assurance was assessed based on the results of cross-checking and assessments of Kappa coefficient between primary health centre and district Health office microscopic personnel and those between district health centers and Department of parasitology, faculty of Medicine, (Gadjah Mada University certified microscopicpersonnel. Result shows that the strength of agreement between the Primary Health Centre and the District Health Office microscopic personnel centers was "good" (kappa 0.61 to 0.80, while those between District Health Office and Department of Parasitology UGM showed poor agreement (0,20– 0,40Keywords : microscopic examination of malaria, Belu District, cross check, KappaAbstrakPemeriksaan sediaan darah masih merupakan baku emas penegakan diagnosis malaria di Indonesia. Pemantapan kualitas mikroskopis malaria merupakan hal penting dalam pemantauan dan pengawasan pemberian obat anti malaria yang tepat

  13. Koefesien Kappa sebagai Indeks Kesepakatan Hasil Diognosis Mikroskopis Malaria di Kabupaten Belu Nusa Tenggara Timur

    Directory of Open Access Journals (Sweden)

    Fridolina Mau


    Full Text Available AbstractBlood slide examination is used as standard malaria diagnosis in Indonesia. Quality assurance for malaria microscopic examination is an important issue in the monitoring and supervision of the administration of antimalarials drugs. This step was done to determine the accuracy of thediagnosis, thus could be used for further evaluation in improving the skills of microscopic health centre personnel. This study aims to determine the accuracy of malaria microscopic examination at Primary health centre and District Health Office personnels in Belu District, Nusa Tenggara Timur.The study was an observational research with cross sectional approach. The competency of primary health center and district healt office microscopist in examining malaria blood smears were evaluated using standard blood smears compared with smears from Passive Case Detection (PCD activities. Performance in preparing blood smear were evaluatied by observation and filling the checklist. The study was conducted in April - Juni 2012 in Belu District, NTT. Quality assurance was assessed based on the results of cross-checking and assessments of Kappa coefficient between primary health centre and district Health office microscopic personnel and those between district health centers and Department of parasitology, faculty of Medicine, (Gadjah Mada University certified microscopicpersonnel. Result shows that the strength of agreement between the Primary Health Centre and the District Health Office microscopic personnel centers was "good" (kappa 0.61 to 0.80, while those between District Health Office and Department of Parasitology UGM showed poor agreement (0,20– 0,40Keywords : microscopic examination of malaria, Belu District, cross check, KappaAbstrakPemeriksaan sediaan darah masih merupakan baku emas penegakan diagnosis malaria di Indonesia. Pemantapan kualitas mikroskopis malaria merupakan hal penting dalam pemantauan dan pengawasan pemberian obat anti malaria yang tepat

  14. Effect of kappa-carrageenan on the properties of poly(N-vinyl pyrrolidone)/kappa-carrageenan blend hydrogel synthesized by {gamma}-radiation technology

    Energy Technology Data Exchange (ETDEWEB)

    Zhai Maolin E-mail:; Ha Hongfei; Yoshii, F.; Makuuchi, K


    A series of hydrogels in the form of rods were prepared from kappa-carrageenan (KC) and poly (N-vinyl pyrrolidone) (PVP) by gamma radiation with {sup 60}Co {gamma} source at room temperature. The properties of the prepared hydrogels, such as the gel strength, gel fraction and swelling behavior were investigated. Incorporation of KC into the PVP/water system increased obviously the gel strength and equilibrium degree of swelling (EDS) of PVP hydrogel. The experimental analyses showed that the crosslinking reaction of PVP was quicker than the degradation of KC at a low dose (less than 30 kGy), and the degradation of KC was inhibited in the PVP/KC mixture system. So an interpenetrating polymer network (IPN) hydrogel composed of PVP (a chemical crosslinking network) and KC (a physical crosslinking network) was proposed here. The existence of different classes of water in this IPN system was shown by water melting curves using DCS. (author)

  15. Dose-related Behavioral, Subjective, Endocrine and Psychophysiological Effects Of the Kappa Opioid Agonist Salvinorin A in Humans (United States)

    Ranganathan, Mohini; Schnakenberg, Ashley; Skosnik, Patrick D.; Cohen, Bruce; Pittman, Brian; Sewell, R. Andrew; D’Souza, Deepak Cyril


    Background Salvia divinorum (Salvia) is an increasingly popular recreational drug amongst adolescents and young adults. Its primary active ingredient, Salvinorin A (SA), a highly selective agonist at the kappa opiate receptor (KOR), is believed to be one of the most potent naturally occurring hallucinogens. However, there is little experimental data on the effects of SA in humans. Methods In a 3-day, double-blind, randomized, crossover, counterbalanced study, the behavioral, subjective, cognitive, psychophysiological and endocrine effects of 0 mg, 8 mg and 12 mg of inhaled SA were characterized in 10 healthy individuals who had previously used Salvia. Results SA produced psychotomimetic effects and perceptual alterations including dissociative and somaesthetic effects, increased plasma cortisol and prolactin and reduced resting EEG spectral power. SA administration was associated with a rapid increase of its levels in the blood. SA did not produce euphoria, cognitive deficits or changes in vital signs. The effects were transient and not dose-related. SA administration was very well tolerated without acute or delayed adverse effects. Conclusions SA produced a wide range of transient effects in healthy subjects. The perceptual altering effects and lack of euphoric effects would explain its intermittent use pattern. Such a profile would also suggest a low addictive potential similar to other hallucinogens and consistent with KOR agonism. Further work is warranted to carefully characterize a full spectrum of its effects in humans, to elucidate the underlying mechanisms involved and to explore the basis for individual variability in its effects. PMID:22817868

  16. The Differential Effects of a Selective Kappa-Opioid Receptor Agonist, U50488, in Guinea Pig Heart Tissues

    Directory of Open Access Journals (Sweden)

    Chi-Feng Hung


    Full Text Available The differential effects of a selective kappa- (κ- opioid receptor agonist, U50488, were elucidated by monitoring the contraction of isolated guinea pig atrial and ventricular muscles. In electrically driven left atria, U50488 in nanomolar concentration range decreased the contractile force. Norbinaltorphimine (norBNI, a selective κ-receptor antagonist, and pertussis toxin (PTX abolished the negative inotropic effect of U50488. In contrast, the inhibitory effect was not affected by the pretreatment of atropine or propranolol. Even though U50488 exerted a negative inotropic effect in the left atrium, it did not affect the contractile force of the right atrium and ventricles paced at 2 Hz. Similarly, the beating rate of the spontaneously beating right atrium was also unaffected by U50488. These results indicate that the activation of κ-opioid receptors can only produce negative inotropic effect in left atria via activation of PTX-sensitive G protein in guinea pigs. The absence of negative inotropic effects in right atria and ventricles suggests that there may be a greater distribution of functional κ-opioid receptors in guinea pig left atria than in right atria and ventricles, and the distribution of the receptors may be species-specific.

  17. NBBA, a synthetic small molecule, inhibits TNF-{alpha}-induced angiogenesis by suppressing the NF-{kappa}B signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Nam Hee; Jung, Hye Jin [Chemical Genomics Laboratory, Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Shibasaki, Futoshi [Translation Research Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506 (Japan); Kwon, Ho Jeong, E-mail: [Chemical Genomics Laboratory, Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of)


    Nuclear factor-{kappa}B (NF-{kappa}B) is a crucial transcription factor that contributes to cancer development by regulating a number of genes involved in angiogenesis and tumorigenesis. Here, we describe (Z)-N-(3-(7-nitro-3-oxobenzo[d][1,2]selenazol-2(3H)-yl)benzylidene) propan-2-amine oxide (NBBA) as a new anti-angiogenic small molecule that targets NF-{kappa}B activity. NBBA showed stronger growth inhibition on human umbilical vein endothelial cells (HUVECs) than on the cancer cell lines we tested. Moreover, NBBA inhibited tumor necrosis factor-alpha (TNF-{alpha})-induced tube formation and invasion of HUVECs. In addition, NBBA suppressed the neovascularization of chorioallantonic membrane from growing chick embryos in vivo. To address the mode of action of the compound, the effect of NBBA on TNF-{alpha}-induced NF-{kappa}B transcription activity was investigated. NBBA suppressed TNF-{alpha}-induced c-Jun N-terminal kinase phosphorylation, which resulted in suppression of transcription of NF-{kappa}B and its target genes, including interleukin-8, interleukin-1{alpha}, and epidermal growth factor. Collectively, these results demonstrated that NBBA is a new anti-angiogenic small molecule that targets the NF-{kappa}B signaling pathway.

  18. Laser ranging ground station development (United States)

    Faller, J. E.


    The employment of ground to conduct radar range measurements of the lunar distance is discussed. The advantages of additional ground stations for this purpose are analyzed. The goals which are desirable for any new type of ranging station are: (1) full time availability of the station for laser ranging, (2) optimization for signal strength, (3) automation to the greatest extent possible, (4) the capability for blind pointing, (5) reasonable initial and modest operational costs, and (6) transportability to enhance the value of the station for geophysical purposes.

  19. Measurement of Q{sub {beta}} values of neutron-rich Tc to Pd isotopes in the mass range A=110 to A=117; Messung von Q{sub {beta}}-Werten neutronenreicher Tc- bis Pd-Isotope im Massenbereich A=110 bis A=117

    Energy Technology Data Exchange (ETDEWEB)

    Kloeckl, Ingo


    The present work describes the measuring of Q{sub {beta}} values of {beta}-instable isotopes of Tc, Ru, Rh and Pd. The mass range A=110 to 117 comprises neutron-rich, short-living isotopes. Due to their small (fission) abundances, few data are known, especially regarding level schemes or gamma radiation. The proton-induced fission and a fast online mass separation was used to produce these nuclides in the IGISOL facility located in Jyvaeskylaein Finland. The {beta},{gamma},X coincidence apparatus used during the experiments allows measuring Q{sub {beta}} values as well as {gamma},X coincidences. The latter represent the basic input data for a calculation of Q{sub {beta}} values out of {beta},{gamma} coincidences. It is so possible to examine nuclides with incomplete level schemes; similarly, these level schemes can be extended using beta,gamma coincidence data. Twelve Q{sub {beta}} values of neutron-rich Tc to Pd isotopes could be determined, yielding nuclear masses, mass defects and neutron separation energies. Eight of them were determined for the first time; another one could be confirmed. For three more, the error of earlier values could be decreased by a factor of nearly ten. The resulting data are of interest for the review of nuclear mass models, they represent also input in astrophysical network calculations. (orig.)

  20. NF-kappa B和AP-1在非小细胞肺癌中的表达%Expression of NF-kappa B and AP-1 in non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    马建群; 张真发; 张林


    背景与目的核因子kappa B(NF-kappa B)和激活蛋白1(AP-1)在细胞凋亡和增生过程中所起的作用逐渐被人们所认知,在肿瘤的形成过程中也扮演着重要的角色.本研究分析了NF-kappa B、AP-1在非小细胞肺癌中的表达,以明确二者之间的相互关系,并进一步研究二者对周期蛋白cyclin D1和caspase 3在非小细胞肺癌中表达的影响.方法应用Western blot检测NF-kappa B、AP-1、cyclin D1和caspase 3在非小细胞肺癌中的蛋白表达,应用RT-PCR检测不同NF-kappa B和AP-1表达的肺癌组织中cyclin D1和caspase 3的mRNA表达.应用相关分析判断NF-kappa B和AP-1的相关性.结果在45例非小细胞肺癌患者中,NF-kappa B和AP-1在肺癌组织中的表达均高于癌旁肺组织中的表达(0.6047比0.2798,P<0.01).在NF-kappa B和AP-1较高表达的肺癌组织中,cyclin D1蛋白表达和mRNA表达均增加(P<0.01),而caspase 3的蛋白表达和mRNA表达减少(P<0.01).相关分析显示NF-kappa B和AP-1有明显的相关性(r=0.800,P<0.01).结论 NF-kappa B和AP-1作为转录因子可能在非小细胞肺癌的形成和发展中起重要作用.

  1. The Value of Value Sets

    DEFF Research Database (Denmark)

    Sløk-Madsen, Stefan Kirkegaard; Christensen, Jesper

    The world over classrooms in business schools are being taught that corporate values can impact performance. The argument is typically that culture matter more than strategy plans and culture can be influenced and indeed changed by a shared corporate value set. While the claim seems intuitively a...... a unique contribution to the effects of investment in shared company values, and to whether agent rationality can be fundamentally changed by committed organizational efforts.......The world over classrooms in business schools are being taught that corporate values can impact performance. The argument is typically that culture matter more than strategy plans and culture can be influenced and indeed changed by a shared corporate value set. While the claim seems intuitively...... and anecdotally true surprisingly little hard evidence has been produced either for or against. This study attempts to rectify this. The study claims that for corporate values to matter they must at least align, and potentially alter, employee decision-making hence their concept of optimality and rational...

  2. Diagnostic Value of 64-Slice Dual-Source CT Coronary Angiography in Patients with Atrial Fibrillation: Comparison with Invasive Coronary Angiography

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jian Jun; Liu, Tie; Feng, Yue; Wu, Wei Feng; Mou, Cai Yun; Zhai, Li Hao [Zhejiang Hospital, Hangzhou (China)


    We wanted to evaluate the image quality and diagnostic value of 64-slice dual-source computed tomography (DSCT) coronary angiography in patients with atrial fibrillation (Afib). The coronary arteries of 22 Afib patients seen on DSCT were classified into 15 segments and the imaging quality (excellent, good, moderate and poor) and significant stenoses ({>=} 50%) were evaluated by two radiologists who were blinded to the conventional coronary angiography (CAG) results. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for detecting important coronary artery stenosis were calculated. McNemar test was used to determine any significant difference between DSCT and CAG, and Cohen's Kappa statistics were calculated for the intermodality and interobserver agreement. The mean heart rate was 89 {+-} 8.3 bpm (range: 80-118 bpm). A range from 250 msec to 300 msec within the RR interval was the optimal reconstruction interval for the patients with Afib. The respective overall sensitivity, specificity, PPV and NPV values were 74%, 97%, 81% and 96% for reader 1 and 72%, 98%, 85% and 96% for reader 2. No significant difference between DSCT and CAG was found for detecting a significant stenosis (reader 1, p = 1.0; reader 2, p = 0.727). Cohen's Kappa statistics demonstrated good intermodality and interobserver agreement. 64-slice DSCT coronary angiography provides good image quality in patients with atrial fibrillation without the need for controlling the heart rate. DSCT can be used for ruling out significant stenosis in patients with atrial fibrillation with its high NPV for detecting in important stenosis.

  3. 高密度范围漫透射视觉密度计的校准及示值误差不确定度分析%Calibration of Diffuse Transmission Visual Densitometer in High Density Range and the Uncertainty Analysis for the Indication Value

    Institute of Scientific and Technical Information of China (English)

    张瑞锋; 程康; 黄清波; 邱黛君; 仵欣; 王磊


    针对漫透射视觉密度计高密度范围(4.0range (4.0range of optical density value(0.03--5.00)D. According to"JJG920-1996 verification regulation of diffuse transmission visual densitometer", the calibration of diffuse transmission visual densitometer in high denstiy range can be realized. And the uncertainty of the indication value was analyzed.

  4. The diagnostic value of time-resolved MR angiography with Gadobutrol at 3 T for preoperative evaluation of lower extremity tumors: Comparison with computed tomography angiography. (United States)

    Wu, Gang; Jin, Teng; Li, Ting; Li, Xiaoming


    To evaluate the diagnostic value of time resolved magnetic resonance angiography with interleaved stochastic trajectory (TWIST) using Gadobutrol for preoperative evaluation of lower extremity tumors. This prospective study was approved by the local Institutional Review Board. 50 consecutive patients (31 men, 19 women, age range 18-80 years, average age 42.7 years) with lower extremity tumors underwent TWIST and computed tomography angiography (CTA). Image quality of TWIST and CTA were evaluated by two radiologists according to a 4-point scale. The degree of arterial stenosis caused by tumor was assessed using TWSIT and CTA separately, and the intra-modality agreement was determined using a kappa test. The number of feeding arteries identified by TWIST was compared with that by CTA using Wilcoxon signed rank test. The ability to identify arterio-venous fistulae (AVF) were compared using a chi-square test. Image quality of TWIST and CTA were rated as 3.88 ± 0.37 and 3.97 ± 0.16, without statistically significant difference (P = 0.135). Intra-modality agreement was excellent for the assessment of arterial stenosis (kappa = 0.806 ± 0.073 for Reader 1, kappa = 0.805 ± 0.073 for Reader 2). Readers identified AVF with TWIST in 27 of 50 cases, and identified AVF with CTA in 14 of 50 (P < 0.001). Mean feeding arteries identified with TWIST was significantly more than that with CTA (2.08 ± 1.72 vs 1.62 ± 1.52, P = 0.02). TWIST is a reliable imaging modality for the assessment of lower extremity tumors. TWIST is comparable to CTA for the identification of AVF and feeding arteries.

  5. Generalized London theory of the mixed state of high-{kappa} superconductors as a projection of the quasiclassical Eilenberger approach

    Energy Technology Data Exchange (ETDEWEB)

    Belova, P., E-mail: [Lappeenranta University of Technology, P.O. Box 20, FI-53851 Lappeenranta (Finland); Petrozavodsk State University, Lenin Str. 33, RU-185640 Petrozavodsk (Russian Federation); Zakharchuk, I. [Lappeenranta University of Technology, P.O. Box 20, FI-53851 Lappeenranta (Finland); Saint-Petersburg Electrotechnical University, Popov Str. 5, RU-197376 St. Petersburg (Russian Federation); Safonchik, M. [Lappeenranta University of Technology, P.O. Box 20, FI-53851 Lappeenranta (Finland); A.F. Ioffe Physico-Technical Institute, St. Petersburg 194021 (Russian Federation); Traito, K.B.; Laehderanta, E. [Lappeenranta University of Technology, P.O. Box 20, FI-53851 Lappeenranta (Finland)


    The generalized London equation in the mixed state of high-{kappa} s-wave pairing superconductors with impurities is considered as a projection of the quasiclassical nonlocal nonlinear Eilenberger theory. Only one fitting parameter - the cutoff parameter {xi}{sub h} - is used in the theory. The distribution of the magnetic field is calculated self-consistently. Both nonlocal effects originated from extended states between the vortices and bound Andreev states in the vortex are taken into account. Comparison with different analytical nonlocal linear approaches (the Kogan-Gurevich, Amin-Franz-Affleck, Kogan-Zhelezina models) including only extended states is done. The importance of the Kramer-Pesch nonlinear effect and the field dependence of the cutoff parameter is emphasized and their strong influence on the variance of the magnetic field is found. The influence of the impurities on the ratio of the cutoff parameter {xi}{sub h} and the Ginzburg-Landau coherence length {xi}{sub c2} is considered. Quasiparticle scattering by impurities and lowering of the temperature reduces the value of {xi}{sub h} to the values much less than {xi}{sub c2}. This is different from the prediction of the local Ginzburg-Landau theory where {xi}{sub h} is scaled by {xi}{sub c2}. It is found that impurities influence by different way on the cutoff parameter {xi}{sub h} and the order parameter coherence length {xi}{sub 1}. The {xi}{sub h} decreases monotonously with the impurity scattering time in contrast to the nonmonotonous behavior of {xi}{sub 1}. The results can be used for analysis of the {mu}SR experimental data.

  6. Tomosynthesis of the thoracic spine: added value in diagnosing vertebral fractures in the elderly

    Energy Technology Data Exchange (ETDEWEB)

    Geijer, Mats [Oerebro University, Department of Radiology, Oerebro (Sweden); Lund University, Department of Clinical Sciences, Lund (Sweden); Gunnlaugsson, Eirikur; Goetestrand, Simon [Lund University and Skaane University Hospital, Department of Medical Imaging and Physiology, Lund (Sweden); Weber, Lars [Lund University, Department of Clinical Sciences, Lund (Sweden); Skaane University Hospital, Department of Radiation Physics, Lund (Sweden); Geijer, Haakan [Oerebro University, Department of Radiology, Faculty of Medicine and Health, Oerebro (Sweden)


    Thoracic spine radiography becomes more difficult with age. Tomosynthesis is a low-dose tomographic extension of radiography which may facilitate thoracic spine evaluation. This study assessed the added value of tomosynthesis in imaging of the thoracic spine in the elderly. Four observers compared the image quality of 50 consecutive thoracic spine radiography and tomosynthesis data sets from 48 patients (median age 67 years, range 55-92 years) on a number of image quality criteria. Observer variation was determined by free-marginal multirater kappa. The conversion factor and effective dose were determined from the dose-area product values. For all observers significantly more vertebrae were seen with tomosynthesis than with radiography (mean 12.4/9.3, P < 0.001) as well as significantly more fractures (mean 0.9/0.7, P = 0.017). The image quality score for tomosynthesis was significantly higher than for radiography, for all evaluated structures. Tomosynthesis took longer to evaluate than radiography. Despite this, all observers scored a clear preference for tomosynthesis. Observer agreement was substantial (mean κ = 0.73, range 0.51-0.94). The calibration or conversion factor was 0.11 mSv/(Gy cm{sup 2}) for the combined examination. The resulting effective dose was 0.87 mSv. Tomosynthesis can increase the detection rate of thoracic vertebral fractures in the elderly, at low added radiation dose. (orig.)

  7. Severe hypernatremia and hyperchloremia in an elderly patient with IgG-kappa-type multiple myeloma

    Directory of Open Access Journals (Sweden)

    Imashuku S


    Full Text Available Shinsaku Imashuku, Naoko Kudo, Kagekatsu KuboDivision of Hematology, Takasago-seibu Hospital, Takasago, JapanAbstract: A 77-year-old male was admitted to hospital after suffering a pelvic bone fracture in a road traffic accident and was incidentally found to have IgG-kappa-type multiple myeloma with hypercalcemia. The patient was also noted to be hypokalemic and had low HCO3-, with possible damage to the distal tubules in the kidneys. When the treatment was begun with bortezomib/dexamethasone/elcatonin and sodium bicarbonate (NaHCO3 in normal saline (equivalent to a daily sodium dose of 200 millimoles per liter [mmol/L], the patient was in a state of poor oral fluid intake. The patient developed hypernatremia and hyperchloremia, with a peak serum sodium and chloride levels of 183 mmol/L and 153 mmol/L, respectively, at the sixth day after the start of treatment. Following the switch of the intravenous infusions from normal saline to soldem 1 and soldem 3 solutions, these high-electrolyte levels gradually returned to normal over the next 7 days. Although the patient showed disturbed consciousness (Japan Coma Scale = JCS-I-3 during the period of electrolyte abnormality, he eventually fully recovered without sequelae. In this patient, we successfully managed the severe hypernatremia/hyperchloremia, caused by the combined effects of intravenous saline burden in a state of poor oral fluid intake, during the treatment for IgG-kappa type multiple myeloma.Keywords: hypernatremia, hyperchloremia, multiple myeloma, IgG-kappa, metabolic acidosis, renal tubular damage

  8. Ketamine suppresses intestinal NF-kappa B activation and proinflammatory cytokine in endotoxic rats

    Institute of Scientific and Technical Information of China (English)

    Jie Sun; Xiao-Dong Wang; Hong Liu; Jian-Guo Xu


    AIM: To investigate the protective effect of ketamine on the endotoxin-induced proinfiammatory cytokines and NFkappa B activation in the intestine.METHODS: Adult male Wistar rats were randomly divided into 6 groups: (a) normal saline control, (b) challenged with endotoxin (5 mg/kg) and treated by saline, (c) challenged with endotoxin (5 mg/kg) and treated by ketamine (0.5 mg/kg),(d) challenged with endotoxin (5 mg/kg) and treated by ketamine (5 mg/kg), (e) challenged with endotoxin (5 mg/kg) and treated by ketamine (50 mg/kg), and (f) saline injected and treated by ketamine (50 mg/kg). After 1, 4 or 6 h, TNF-α and IL-6 mRNA were investigated in the tissues of the intestine (jejunum) by RT-PCR. TNF-α and IL-6 were measured by ELISA. We used electrophoretic mobility shift assay (EMSA) to investigate NF-kappa B activity in the intestine.RESULTS: NF-kappa B activity, the expression of TNF-α and IL-6 were enhanced in the intestine by endotoxin.Ketamine at a dose of 0.5 mg/kg could suppress endotoxininduced TNF-α mRNA and protein elevation and inhibit NFkappa B activation in the intestine. However the least dosage of ketamine to inhibit IL-6 was 5 mg/kg in our experiment.CONCLUSION: Ketamine can suppress endotoxin-induced production of proinflammatory cytokines such as TNF-α and IL-6 production in the intestine. This suppressive effect may act through inhibiting NF-kappa B.

  9. Managing pain in chronic pancreatitis:therapeutic value of opioid treatment

    DEFF Research Database (Denmark)

    Eisenberg, Elon; Ståhl, Camilla; Drewes, Asbjørn M;


    The value of opioid pharmacotherapy in the management of chronic pancreatitis pain is described. The role of kappa receptor opioid agonists and specifically oxycodone as compared to other opioid agonists is discussed. Limitations in the published studies on this topic are delineated...

  10. CARMA3 is overexpressed in colon cancer and regulates NF-{kappa}B activity and cyclin D1 expression

    Energy Technology Data Exchange (ETDEWEB)

    Miao, Zhifeng; Zhao, Tingting; Wang, Zhenning; Xu, Yingying; Song, Yongxi; Wu, Jianhua [Department of General Surgery, First Affiliated Hospital of China Medical University, Shenyang (China); Xu, Huimian, E-mail: [Department of General Surgery, First Affiliated Hospital of China Medical University, Shenyang (China)


    Highlights: Black-Right-Pointing-Pointer CARMA3 expression is elevated in colon cancers. Black-Right-Pointing-Pointer CARMA3 promotes proliferation and cell cycle progression in colon cancer cells. Black-Right-Pointing-Pointer CARMA3 upregulates cyclinD1 through NF-{kappa}B activation. -- Abstract: CARMA3 was recently reported to be overexpressed in cancers and associated with the malignant behavior of cancer cells. However, the expression of CARMA3 and its biological roles in colon cancer have not been reported. In the present study, we analyzed the expression pattern of CARMA3 in colon cancer tissues and found that CARMA3 was overexpressed in 30.8% of colon cancer specimens. There was a significant association between CARMA3 overexpression and TNM stage (p = 0.0383), lymph node metastasis (p = 0.0091) and Ki67 proliferation index (p = 0.0035). Furthermore, knockdown of CARMA3 expression in HT29 and HCT116 cells with high endogenous expression decreased cell proliferation and cell cycle progression while overexpression of CARMA3 in LoVo cell line promoted cell proliferation and facilitated cell cycle transition. Further analysis showed that CARMA3 knockdown downregulated and its overexpression upregulated cyclin D1 expression and phospho-Rb levels. In addition, we found that CARMA3 depletion inhibited p-I{kappa}B levels and NF-{kappa}B activity and its overexpression increased p-I{kappa}B expression and NF-{kappa}B activity. NF-{kappa}B inhibitor BAY 11-7082 reversed the role of CARMA3 on cyclin D1 upregulation. In conclusion, our study found that CARMA3 is overexpressed in colon cancers and contributes to malignant cell growth by facilitating cell cycle progression through NF-{kappa}B mediated upregulation of cyclin D1.

  11. NOTCH1 can initiate NF-kappaB activation via cytosolic interactions with components of the T cell signalosome

    Directory of Open Access Journals (Sweden)

    Lisa M Minter


    Full Text Available T cell stimulation requires the input and integration of external signals. Signaling through the T cell receptor (TCR is known to induce formation of the membrane-tethered CBM complex, comprising CARMA1, BCL10 and MALT1, which is required for TCR-mediated NF-kappaB activation. TCR signaling has been shown to activate NOTCH proteins, transmembrane receptors also implicated in NF-kappaB activation. However, the link between TCR-mediated NOTCH signaling and early events leading to induction of NF-kappaB activity remains unclear. In this report, we demonstrate a novel cytosolic function for NOTCH1 and show that it is essential to CBM complex formation. Using a model of skin allograft rejection, we show in vivo that NOTCH1 acts in the same functional pathway as PKCtheta, a T cell-specific kinase important for CBM assembly and classical NF-kappaB activation. We further demonstrate in vitro NOTCH1 associates physically with PKCtheta and CARMA1 in the cytosol. Unexpectedly, when NOTCH1 expression was abrogated using RNAi approaches, interactions between CARMA1, BCL10 and MALT1 were lost. This failure in CBM assembly reduced IkappaBalpha phosphorylation and diminished NF-kappaB-DNA binding. Finally, using a luciferase gene reporter assay, we show the intracellular domain of NOTCH1 can initiate robust NF-kappaB activity in stimulated T cells, even when NOTCH1 is excluded from the nucleus through modifications that restrict it to the cytoplasm or hold it tethered to the membrane. Collectively, these observations provide evidence that NOTCH1 may facilitate early events during T cell activation by nucleating the CBM complex and initiating NF-kappaB signaling.

  12. Nuclear IL-33 is a transcriptional regulator of NF-{kappa}B p65 and induces endothelial cell activation

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yeon-Sook; Park, Jeong Ae; Kim, Jihye; Rho, Seung-Sik; Park, Hyojin [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Kim, Young-Myeong [Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon (Korea, Republic of); Kwon, Young-Guen, E-mail: [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of)


    Highlights: Black-Right-Pointing-Pointer IL-33 as nuclear factor regulated expression of ICAM-1 and VCAM-1. Black-Right-Pointing-Pointer Nuclear IL-33 increased the transcription of NF-{kappa}B p65 by binding to the p65 promoter. Black-Right-Pointing-Pointer Nuclear IL-33 controls NF-{kappa}B-dependent inflammatory responses. -- Abstract: Interleukin (IL)-33, an IL-1 family member, acts as an extracellular cytokine by binding its cognate receptor, ST2. IL-33 is also a chromatin-binding transcriptional regulator highly expressed in the nuclei of endothelial cells. However, the function of IL-33 as a nuclear factor is poorly defined. Here, we show that IL-33 is a novel transcriptional regulator of the p65 subunit of the NF-{kappa}B complex and is involved in endothelial cell activation. Quantitative reverse transcriptase PCR and Western blot analyses indicated that IL-33 mediates the expression of intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 in endothelial cells basally and in response to tumor necrosis factor-{alpha}-treatment. IL-33-induced ICAM-1/VCAM-1 expression was dependent on the regulatory effect of IL-33 on the nuclear factor (NF)-{kappa}B pathway; NF-{kappa}B p65 expression was enhanced by IL-33 overexpression and, conversely, reduced by IL-33 knockdown. Moreover, NF-{kappa}B p65 promoter activity and chromatin immunoprecipitation analysis revealed that IL-33 binds to the p65 promoter region in the nucleus. Our data provide the first evidence that IL-33 in the nucleus of endothelial cells participates in inflammatory reactions as a transcriptional regulator of NF-{kappa}B p65.

  13. Radiosensitization by overexpression of the nonphosphorylation form of I{kappa}B-{alpha} in human glioma cells

    Energy Technology Data Exchange (ETDEWEB)

    Honda, Naoko; Yagi, Kasumi; Ding, Gui-Rong; Miyakoshi, Junji [Kyoto Univ. (Japan). Graduate School of Medicine


    To assess the role of NF-{kappa}B in cellular radiosensitivity, we constructed mutated I{kappa}B expression plasmids for SY-I{kappa}B (with mutations at residues of 32, 36 and 42) expression in human malignant glioma cells (radiosensitive MO54 and radioresistant T98 cells), giving respective cell types referred to as MO54-SY4 and T98-SY14. Both of the clones expressing SY-I{kappa}B became radiosensitive, compared with the parental MO54 and T98 cells. A treatment with herbimycin A or genistein did not change the radiosensitivity of cells expressing SY-I{kappa}B, but made both the MO54 and T98 parental cells more sensitive to ionizing radiation. A treatment with TNF-{alpha} induced DNA fragmentation and apoptosis in cells expressing SY-I{kappa}B, but not in MO54 and T98 cells. The survival after X-ray exposure of the parental MO54 cells was slightly increased by a TNF-{alpha} treatment, but that of the parental T98 cells did not change. The change in sensitivity to ultra-violet (UV) radiation and adriamycin in MO54-SY4 cells was very similar to that for X-ray sensitivity, but no change was observed in T98-SY14 cells. Significant sublethal damage repair was observed in T98 cells, whereas MO54 cells showed little repair activity. The expression of p53 was enhanced in the parental MO54 cells, while the p53 levels in the MO54-SY4, and in the parent and clonal T98 cells, did not change. Our data suggest that the serine and tyrosine phosphorylation of I{kappa}B-{alpha} may play a role in determining the radiosensitivity of malignant glioma cells. (author)

  14. Synthesis of [{sup 3}]DIPPA: a potent irreversible antagonist selective for the {kappa} opioid receptor

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Anchih; Portoghese, P.S. [Minnesota Univ., Minneapolis, MN (United States). College of Pharmacy; Trometer, J.D. [E.I. Du Pont de Nemours and Co., Inc., Boston, MA (United States)


    2-(3,4-Dichlorophenyl)-N-methyl-N-[(1S)-1-(3-isothiocyanatophe nyl)-2-(1-pyrrolidinyl)ethyl]acetamide (1,DIPPA) has been previously reported to be an opioid receptor affinity label that produces selective and long-lasting {kappa} opioid receptor antagonism in mice. High specific activity [{sup 3}H]DIPPA (39.7 Ci/mmol) was prepared by bromination and catalytic tritiation of the amino precursor of DIPPA followed by conversion to the isothiocyanate with thiophosgene. (Author).

  15. Targeting Nuclear Factor kappa B for the Treatment of Prostate Cancer (United States)


    enhancer involving C/EBP-beta and NF-kappaB. Mol Cell Biol 17:6970-81, 1997 8. Zong WX, Edelstein LC, Chen C, et al: The prosurvival Bcl-2 homolog Bfl-1/A1...9136-41., 1999 10. Baldini N: Multidrug resistance--a multiplex phenomenon. Nat Med 3:378-80, 1997 11. Wang CY, Mayo MW, Baldwin AS, Jr.: TNF- and cancer...Titer the frequency and location of NF-KB by staining for the p6 5 96 AQu .... Non-radioactive Cell Proliferation Assay (Promega subunit of the Rel

  16. NF-{kappa}B suppresses HIF-1{alpha} response by competing for P300 binding

    Energy Technology Data Exchange (ETDEWEB)

    Mendonca, Daniela B.S., E-mail: [Universidade Catolica de Brasilia, Pos-Graduacao em Ciencias Genomicas e Biotecnologia, SGAN Quadra 916, Av. W5 Norte, 70790-160 Brasilia, DF (Brazil); Bone Biology and Implant Therapy Laboratory, Department of Prosthodontics, University of North Carolina at Chapel Hill, 330 Brauer Hall, CB 7450, Chapel Hill, NC 27599 (United States); Mendonca, Gustavo [Universidade Catolica de Brasilia, Pos-Graduacao em Ciencias Genomicas e Biotecnologia, SGAN Quadra 916, Av. W5 Norte, 70790-160 Brasilia, DF (Brazil); Bone Biology and Implant Therapy Laboratory, Department of Prosthodontics, University of North Carolina at Chapel Hill, 330 Brauer Hall, CB 7450, Chapel Hill, NC 27599 (United States); Aragao, Francisco J.L. [Universidade Catolica de Brasilia, Pos-Graduacao em Ciencias Genomicas e Biotecnologia, SGAN Quadra 916, Av. W5 Norte, 70790-160 Brasilia, DF (Brazil); Embrapa Recursos Geneticos e Biotecnologia, Laboratorio de Introducao e Expressao de Genes, PqEB W5 Norte, 70770-900 Brasilia, DF (Brazil); Cooper, Lyndon F., E-mail: [Bone Biology and Implant Therapy Laboratory, Department of Prosthodontics, University of North Carolina at Chapel Hill, 330 Brauer Hall, CB 7450, Chapel Hill, NC 27599 (United States)


    Research highlights: {yields} p65 completely blocked HIF-1{alpha} activity at the HRE on different cell lines. {yields} p65 caused minor changes in HIF-1{alpha} and HIF-1{alpha} target genes mRNA expression. {yields} p65 reduced transcription of VEGF promoter. {yields} p65 competes with HIF-1{alpha} for p300. -- Abstract: Hypoxia has emerged as a key determinant of osteogenesis. HIF-1{alpha} is the transcription factor mediating hypoxia responses that include induction of VEGF and related bone induction. Inflammatory signals antagonize bone repair via the NF-{kappa}B pathway. The present investigation explored the functional relationship of hypoxia (HIF-1{alpha} function) and inflammatory signaling (NF-{kappa}B) in stem like and osteoprogenitor cell lines. The potential interaction between HIF-1{alpha} and NF-{kappa}B signaling was explored by co-transfection studies in hFOB with p65, HIF-1{alpha} and 9x-HRE-luc or HIF-1{alpha} target genes reporter plasmids. Nuclear cross-talk was directly tested using the mammalian Gal4/VP16 two-hybrid, and confirmed by co-immunoprecipitation/western blotting assays. The results show that inflammatory stimulation (TNF-{alpha} treatment) causes a marked inhibition of HIF-1{alpha} function at the HRE in all cell lines studied. Also, co-transfection with p65 expression vector leads to reduced hVEGFp transcription after DFO-induced hypoxia. However, TNF-{alpha} treatment had little effect on HIF-1{alpha} mRNA levels. The functional interaction of Gal4-HIF-1{alpha} and VP16-p300 fusion proteins is effectively blocked by expression of p65 in a dose dependent manner. It was concluded that NF-{kappa}B-mediated inflammatory signaling is able to block HIF-1{alpha} transactivation at HRE-encoding genes by direct competition for p300 binding at the promoter. Inflammation may influence the stem cell niche and tissue regeneration by influencing cellular responses to hypoxia.

  17. An interesting cause of esophageal ulcer etiology: Multiple myeloma of IgG kappa subtype (United States)

    Pehlivan, Yavuz; Sevinc, Alper; Sari, Ibrahim; Gulsen, Murat T; Buyukberber, Mehmet; Kalender, Mehmet E; Camci, Celalettin


    Multiple myeloma is a neoplasm of mature and immature plasma cells. A 50-year-old woman with lumbago, dysphagia, and left arm pain was presented. Upper endoscopical examination was performed. There was an exudate-covered ulcer in the distal esophagus, located at 30-32 cm from the incisors, covering the whole mucosa. Histopathological examination of the specimens obtained from the lesion showed the involvement of plasma cells consistent with multiple myeloma of IgG kappa subtype. Esophageal involvement of multiple myeloma should be kept in mind in patients presenting with dysphagia. PMID:16610044

  18. Dust charge fluctuation effects on Langmuir waves with kappa distributed electrons (United States)

    Jamshidi, M.; Rouhani, M. R.; Hakimi Pajouh, H.


    Using a kinetic description, dust charge fluctuations due to the inelastic collisions between dust particles and plasma particles are studied in unmagnetized dusty plasmas. Most astrophysical and space plasmas are observed to have non-Maxwellian high energy tail. Therefore, a kappa distribution for electrons in the equilibrium is assumed. The dispersion relation and damping rates for Langmuir waves are obtained. Considering the dust charge fluctuations increases the damping rate of Langmuir waves. It is shown that the damping rate of Langmuir waves depends on the spectral index and the dust density parameter.

  19. Simultaneous presentation of kappa-restricted chronic lymphocytic leukemia and lambda light chain AL amyloidosis. (United States)

    von Keudell, Gottfried; Sanchorawala, Vaishali; O'Hara, Carl; C Seldin, David; Sloan, J Mark


    We report on a 58-year-old man who presented with simultaneous kappa-restricted chronic lymphocytic leukemia (CLL) and a lambda-restricted plasma cell dyscrasia causing AL amyloidosis involving the kidney and GI tract. While monoclonal immunoglobulins occasionally produced by CLL has previously been implicated in AL amyloidosis, this is the first case of AL amyloidosis resulting from a distinct plasma cell dyscrasia that is not clonally related to the concurrent CLL. Appropriate treatment depended on detailed pathologic diagnosis of both disease processes.

  20. PENGARUH KONSUMSI KAPPA-KARAGENAN TERHADAP GLUKOSA DARAH TIKUS WISTAR (Ratus norvegicus DIABETES [The Effect of Kappa-Carrageenan Consumption on Blood Glucose Level of Diabetic Wistar Rat (Ratus norwegicus

    Directory of Open Access Journals (Sweden)



    Full Text Available The effect of kappa-carrageenan consumption on blood glucose level were studied on diabetic male wistar rat (Ratus norvegicus.The rats were made diabetic by aloxan injection, and then were given that a ration contains 5, 10, 15, 20% (w/w kappa-carrageenan, standard ration (negative control, and parental glibenklamid (positive control. The results showed that the standard ration could not reduce blood glucose from hyperglycemic to normal level, while the ration contained kappacarrageenan could. The higher kappa-carrageenan seaweed level in the ration has higher capacity to decrease blood glucose level. The ration containing 20% and 15% kappa-carrageenan could reduce blood glucose in 18 and 21 days, respectively.The effect of this ration was similar to that of glibenklamid which reduced blood glucose to normal level in 18 days. The ration containing 5 and 10% kappa-carrageenan could reduce blood glucose level; Blood glucose leve return to normal on the 21st day.

  1. Genus Ranges of Chord Diagrams. (United States)

    Burns, Jonathan; Jonoska, Nataša; Saito, Masahico


    A chord diagram consists of a circle, called the backbone, with line segments, called chords, whose endpoints are attached to distinct points on the circle. The genus of a chord diagram is the genus of the orientable surface obtained by thickening the backbone to an annulus and attaching bands to the inner boundary circle at the ends of each chord. Variations of this construction are considered here, where bands are possibly attached to the outer boundary circle of the annulus. The genus range of a chord diagram is the genus values over all such variations of surfaces thus obtained from a given chord diagram. Genus ranges of chord diagrams for a fixed number of chords are studied. Integer intervals that can be, and those that cannot be, realized as genus ranges are investigated. Computer calculations are presented, and play a key role in discovering and proving the properties of genus ranges.

  2. Fair Value or Market Value?


    Bogdan Cosmin Gomoi; Lavinia Denisia Cuc; Robert Almaşi


    When taking into consideration the issue of defining the “fair value” concept, those less experimented in the area often fall in the “price trap”, which is considered as an equivalent of the fair value of financial structures. This valuation basis appears as a consequence of the trial to provide an “accurate image” by the financial statements and, also, as an opportunity for the premises offered by the activity continuing principle. The specialized literature generates ample controversies reg...

  3. Epicatechin induces NF-kappaB, activator protein-1 (AP-1) and nuclear transcription factor erythroid 2p45-related factor-2 (Nrf2) via phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) and extracellular regulated kinase (ERK) signalling in HepG2 cells. (United States)

    Granado-Serrano, Ana Belén; Martín, María Angeles; Haegeman, Guy; Goya, Luis; Bravo, Laura; Ramos, Sonia


    The dietary flavonoid epicatechin has been reported to exhibit a wide range of biological activities. The objective of the present study was to investigate the time-dependent regulation by epicatechin on the activity of the main transcription factors (NF-kappaB, activator protein-1 (AP-1) and nuclear transcription factor erythroid 2p45-related factor (Nrf2)) related to antioxidant defence and survival and proliferation pathways in HepG2 cells. Treatment of cells with 10 microm-epicatechin induced the NF-kappaB pathway in a time-dependent manner characterised by increased levels of IkappaB kinase (IKK) and phosphorylated inhibitor of kappaB subunit-alpha (p-IkappaBalpha) and proteolytic degradation of IkappaB, which was consistent with an up-regulation of the NF-kappaB-binding activity. Time-dependent activation of the AP-1 pathway, in concert with enhanced c-Jun nuclear levels and induction of Nrf2 translocation and phosphorylation were also demonstrated. Additionally, epicatechin-induced NF-kappaB and Nrf2 were connected to reactive oxygen species intracellular levels and to the activation of cell survival and proliferation pathways, being phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) and extracellular regulated kinase (ERK) associated to Nrf2 modulation and ERK to NF-kappaB induction. These data suggest that the epicatechin-induced survival effect occurs by the induction of redox-sensitive transcription factors through a tight regulation of survival and proliferation pathways.

  4. Model-based uncertainty in species range prediction

    DEFF Research Database (Denmark)

    Pearson, R. G.; Thuiller, Wilfried; Bastos Araujo, Miguel;


    Aim Many attempts to predict the potential range of species rely on environmental niche (or 'bioclimate envelope') modelling, yet the effects of using different niche-based methodologies require further investigation. Here we investigate the impact that the choice of model can have on predictions...... day (using the area under the receiver operating characteristic curve (AUC) and kappa statistics) and by assessing consistency in predictions of range size changes under future climate (using cluster analysis). Results Our analyses show significant differences between predictions from different models......, with predicted changes in range size by 2030 differing in both magnitude and direction (e.g. from 92% loss to 322% gain). We explain differences with reference to two characteristics of the modelling techniques: data input requirements (presence/absence vs. presence-only approaches) and assumptions made by each...

  5. Coffee and Maillard products activate NF-kappaB in macrophages via H2O2 production. (United States)

    Muscat, Sonja; Pelka, Joana; Hegele, Jörg; Weigle, Bernd; Münch, Gerald; Pischetsrieder, Monika


    In this study, we investigated the immunomodulatory activity of coffee and Maillard reaction products on macrophages in vitro. Stimulation of macrophages with coffee, but not with raw coffee extract in PBS, led to a 13-fold increased nuclear NF-kappaB translocation. A Maillard reaction mixture (25 mM D-ribose/L-lysine, 30 min at 120 degrees C) increased NF-kappaB translocation 18-fold (in PBS) or six-fold (in medium). MRPs also induced a two-fold increased NF-kappaB translocation in untransfected human embryonic kidney (HEK) cells as well as in HEK cells stably transfected with the receptor for advanced glycation endproducts (RAGE), indicating that the effect was not RAGE mediated. On the other hand, catalase totally abolished coffee- and MRP-induced NF-kappaB translocation. Consequently, up to 366 microM hydrogen peroxide was measured in the coffee preparation and Maillard mixtures used for cell stimulation. Stimulation of macrophages with MRPs did not lead to significantly increased IL-6 or NO release. Thus, it can be concluded that coffee and MRPs induce NF-kappaB translocation in macrophages via the generation of hydrogen peroxide.

  6. Analgesia produced by exposure to 2450-MHz radiofrequency radiation (RFR) is mediated by brain mu- and kappa-opioid receptors

    Energy Technology Data Exchange (ETDEWEB)

    Salomon, G.; Park, E.J.; Quock, R.M. (Univ. of Illinois, Rockford (United States))


    This study was conducted to identify the opioid receptor subtype(s) responsible for RFR-induced analgesia. Male Swiss Webster mice, 20-25 g, were exposed to 20 mW/cm{sup 2} RFR in a 2,450-MHz waveguide system for 10 min, then tested 15 min later in the abdominal constriction paradigm which detects {mu}- and {kappa}-opioid activity. Immediately following RFR exposure, different groups of mice were pretreated intracerebroventricularly with different opioid receptor blockers with selectivity for {mu}- or {kappa}-opioid receptors. Results show that RFR-induced analgesia was attenuated by higher but not lower doses of the non-selective antagonist naloxone, but the selective {mu}-opioid antagonist {beta}-funaltrexamine and by the selective {kappa}-opioid antagonist norbinaltorphimine. RFR-induced analgesia was also reduced by subcutaneous pretreatment with 5.0 mg/kg of the {mu}-/{kappa}-opioid antagonist({minus})-5,9-diethyl-{alpha}-5,9-dialkyl-2{prime}-hydroxy-6,7-benzomorphan(MR-2266). These findings suggest that RFR-induced analgesia may be mediated by both {mu}- and {kappa}-opioid mechanisms.

  7. The Central Reinforcing Properties of Ethanol Are Mediated by Endogenous Opioid Systems: Effects of Mu and Kappa Opioid Antagonists.

    Directory of Open Access Journals (Sweden)

    Norman E. Spear


    Full Text Available Endogenous opioid systems are implicated in the reinforcing effects of ethanol and may play a substantial role in modulating the central reinforcing effects of ethanol early in ontogeny. This possibility was explored in the present study through the use of an olfactory conditioning paradigm with centrally administered ethanol serving as an unconditioned stimulus (US. In Experiment 1, newborn rat pups were treated with either a selective mu antagonist CTOP or kappa selective antagonist nor-BNI prior to olfactory conditioning. Experiment 2 tested the effectiveness of an alternative, shorter-duration kappa opioid antagonist GNTI in altering ethanol reinforcement. Experiment 3 investigated whether the effectiveness of pharmacological blockade of opioid receptors was due to the disruption of learning per se using an olfactory aversive conditioning paradigm with intraoral quinine serving as a US. Central administration of either mu or kappa opioid antagonists prior to conditioning disrupted the reinforcing effects of ethanol in newborn rats. The kappa opioid antagonist GNTI was as effective as nor-BNI. These effects of opioid antagonists on ethanol reinforcement are unlikely to be due to a disruption of all types of conditioning, since CTOP did not affect aversive reinforcement to intraoral infusions of quinine. The present results support the hypothesis that in newborn rats, the reinforcing properties of ethanol are mediated by the endogenous activity at mu and kappa opioid receptors.

  8. Evaluation of the kappa-opioid receptor-selective tracer [{sup 11}C]GR103545 in awake rhesus macaques

    Energy Technology Data Exchange (ETDEWEB)

    Schoultz, Bent W. [University of Oslo, Department of Chemistry, Oslo (Norway); Hjornevik, Trine; Willoch, Frode [University of Oslo, Centre for Molecular Biology and Neuroscience and Institute of Basic Medical Sciences, Oslo (Norway); Akershus University Hospital, Department of Nuclear Medicine, Loerenskog (Norway); Marton, Janos [ABX Advanced Biochemical Compounds GmbH, Radeberg (Germany); Noda, Akihiro; Murakami, Yoshihiro; Miyoshi, Sosuke; Nishimura, Shintaro [Medical and Pharmacological Research Center Foundation, Basic Research Department, Hakui City, Ishikawa (Japan); Aarstad, Erik [University College of London, Institute of Nuclear Medicine, London (United Kingdom); Drzezga, Alexander [Technische Universitaet Muenchen, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany); Matsunari, Ichiro [Medical and Pharmacological Research Center Foundation, Clinical Research Department, Hakui City, Ishikawa (Japan); Henriksen, Gjermund [University of Oslo, Department of Chemistry, Oslo (Norway); Technische Universitaet Muenchen, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany)


    The recent development in radiosynthesis of the {sup 11}C-carbamate function increases the potential of [{sup 11}C]GR103545, which for the last decade has been regarded as promising for imaging the kappa-opioid receptor ({kappa}-OR) with PET. In the present study, [{sup 11}C]GR103545 was evaluated in awake rhesus macaques. Separate investigations were performed to clarify the OR subtype selectivity of this compound. Regional brain uptake kinetics of [{sup 11}C]GR103545 was studied 0-120 min after injection. The binding affinity and opioid subtype selectivity of [{sup 11}C]GR103545 was determined in cells transfected with cloned human opioid receptors. In vitro binding assays demonstrated a high affinity of GR103545 for {kappa}-OR (K{sub i} = 0.02 {+-}0.01 nM) with excellent selectivity over {mu}-OR (6 x 10{sup 2}-fold) and {delta}-OR (2 x 10{sup 4}-fold). PET imaging revealed a volume of distribution (V{sub T}) pattern consistent with the known distribution of {kappa}-OR, with striatum = temporal cortex > cingulate cortex > frontal cortex > parietal cortex > thalamus > cerebellum. [{sup 11}C]GR103545 is selective for {kappa}-OR and holds promise for use to selectively depict and quantify this receptor in humans by means of PET. (orig.)

  9. Oligo-carrageenan kappa increases C, N and S assimilation, auxin and gibberellin contents, and growth in Pinus radiata trees

    Institute of Scientific and Technical Information of China (English)

    Silvia Saucedo; Rodrigo A Contreras; Alejandra Moenne


    Oligo-carrageenans (OCs) obtained from pure carrageenans extracted from marine red algae stimulate growth by enhancing photosynthesis and basal metabolism in tobacco plants and Eucalyptus trees. In addition, OCs stimulate secondary metabolism, increasing the level of metabolites involved in defense against pathogens. In this work, we analyzed the effect of OC kappa on the increase in height, in activities of basal metabolism enzymes in-volved in carbon, nitrogen and sulphur assimilation, ribu-lose 1,5 biphosphate carboxylase/oxygenase (rubisco), glutamate dehydrogenase (GDH) and O-acetylserine thiol-lyase (OASTL), and in the level of growth-promoting hormones, the auxin indole acetic acid (IAA) and the gibberellin GA3, in pine (Pinus radiata) trees treated with OC kappa at concentrations of 1 and 5 mg mL-1 and cultivated for 9 months without additional treatment. Pines treated with OC kappa at 1 mg mL-1 showed a similar increase in height but displayed a higher increased in total chlorophyll, activities of rubisco, GDH and OASTL and level of IAA and GA3 than those treated with OC kappa at 5 mg mL-1. Thus, OC kappa stimulates growth and basal metabolism and increases the level of growth-promoting hormones in pine trees, mainly at 1 mg mL-1.

  10. Effect of GNTI,a kappa opioid receptor antagonist, on MK-801-induced hyperlocomotion and stereotypy in mice

    Institute of Scientific and Technical Information of China (English)

    Chun-ting QI; Hong ZOU; Chen-hao ZHANG; Qing-lian XIE; Mei-lei JIN; Lei YU


    Aim:To examine the effect of GNTI[5'-guanidinyl-17-(cyclopropylmethyl)-6,7-dehydro-4,-5α-epoxy-3-14-dihydroxy-6,7-2',3'-indolomorphinan],a selective antagonist for the kappa opioid receptor,in the MK-801 (dizocilpine maleate)-induced behavioral model of psychosis in schizophrenia as a way to explore the involvement of the kappa opioid receptor in modulating psychotic symptoms of schizophrenia.Methods:Two doses 0f MK-801 (0.3 mg/kg and 0.6 mg/kg) were administered by systemic injection in mice to induce psychosis-like behavior as a rodent schizophrenia model, preceded by an injection of different doses of GNTI. Both locomotion and stereotypy were measured as the behavioral endpoints for quantitative analysis.Results:GNTI inhibited MK-801-induced hyperlocomotion and stereotypy.In particular,GNTI showed differential modulation of stereotypy induced by 0.3 mg/kg VS 0.6 mg/kg MK-801.Conclusion:Antagonism of kappa opioid receptors attenuates MK-801-induced behavior,suggesting a potential involvement of the kappa opioid receptor in psychosis-like symptoms of schizophrenia.GNTI aDpears to be a useful pharmacological tool to explore the kappa opioid receptor function in vivo.

  11. Ghrelin inhibits the development of acute pancreatitis and nuclear factor kappaB activation in pancreas and liver. (United States)

    Zhou, Xiaolei; Xue, Chengrui


    To investigate the influence of ghrelin on the development of severe acute pancreatitis (SAP) and the expression of nuclear factor kappaB (NF-kappaB) p65 in the pancreas and liver. Severe acute pancreatitis was induced in rat by sodium taurocholate injection in the pancreaticobiliary duct. Ghrelin was administrated twice at the dose 10 or 20 nmol/kg per injection, respectively. Then, serum amylase activity; serum tumor necrosis factor alpha, interleukin 1beta, and interleukin 6 concentrations; and morphological signs of pancreatitis and hepatic damage were measured. Meanwhile, determination of pancreatic and hepatic NF-kappaB p65 expression was performed by Western blotting and immunohistochemistry. The serumal parameters increased, and morphological damages were observed in the pancreas and liver in SAP rats. Nuclear factor kappaB p65 expression was significantly higher in the pancreas and liver than sham-operated rats (P pancreas and liver. Ghrelin inhibits the development of acute pancreatitis induced by sodium taurocholate. It exerts the therapeutic effects through inhibiting NF-kappaB expression, thereby blocks the inflammatory signal transduction pathway and reduces the release of inflammatory media and cytokines.

  12. Quercetin modulates NF-kappa B and AP-1/JNK pathways to induce cell death in human hepatoma cells. (United States)

    Granado-Serrano, Ana Belén; Martín, María Angeles; Bravo, Laura; Goya, Luis; Ramos, Sonia


    Quercetin, a dietary flavonoid, has been shown to possess anticarcinogenic properties, but the precise molecular mechanisms of action are not thoroughly elucidated. The aim of this study was to investigate the regulatory effect of quercetin (50 microM) on two main transcription factors (NF-kappa B and AP-1) related to survival/proliferation pathways in a human hepatoma cell line (HepG2) over time. Quercetin induced a significant time-dependent inactivation of the NF-kappa B pathway consistent with a downregulation of the NF-kappa B binding activity (from 15 min onward). These features were in concert with a time-dependent activation (starting at 15 min and maintained up to 18 h) of the AP-1/JNK pathway, which played an important role in the control of the cell death induced by the flavonoid and contributed to the regulation of survival/proliferation (AKT, ERK) and death (caspase-3, p38, unbalance of Bcl-2 proapoptotic and antiapoptotic proteins) signals. These data suggest that NF-kappa B and AP-1 play a main role in the tight regulation of survival/proliferation pathways exerted by quercetin and that the sustained JNK/AP-1 activation and inhibition of NF-kappa B provoked by the flavonoid induced HepG2 death.

  13. Glucocorticoid-induced TNF receptor expression by T cells is reciprocally regulated by NF-kappaB and NFAT. (United States)

    Zhan, Yifan; Gerondakis, Steve; Coghill, Elise; Bourges, Dorothee; Xu, Yuekang; Brady, Jamie L; Lew, Andrew M


    Although the transcription factor Foxp3 is implicated in regulating glucocorticoid-induced TNF receptor (GITR) expression in the T regulatory cell lineage, little is known about how GITR is transcriptionally regulated in conventional T cells. In this study, we provide evidence that TCR-mediated GITR expression depends on the ligand affinity and the maturity of conventional T cells. A genetic dissection of GITR transcriptional control revealed that of the three transcription factors downstream of the classical NF-kappaB pathway (RelA, cRel, and NF-kappaB1), RelA is a critical positive regulator of GITR expression, although cRel and NF-kappaB1 also play a positive regulatory role. Consistent with this finding, inhibiting NF-kappaB using Bay11-7082 reduces GITR up-regulation. In contrast, NFAT acts as a negative regulator of GITR expression. This was evidenced by our findings that agents suppressing NFAT activity (e.g., cyclosporin A and FK506) enhanced TCR-mediated GITR expression, whereas agents enhancing NFAT activity (e.g., lithium chloride) suppressed TCR-mediated GITR up-regulation. Critically, the induction of GITR was found to confer protection to conventional T cells from TCR-mediated apoptosis. We propose therefore that two major transcriptional factors activated downstream of the TCR, namely, NF-kappaB and NFAT, act reciprocally to balance TCR-mediated GITR expression in conventional T cells, an outcome that appears to influence cell survival.

  14. A role for NRAGE in NF-kappaB activation through the non-canonical BMP pathway. (United States)

    Matluk, Nicholas; Rochira, Jennifer A; Karaczyn, Aldona; Adams, Tamara; Verdi, Joseph M


    Previous studies have linked neurotrophin receptor-interacting MAGE protein to the bone morphogenic protein signaling pathway and its effect on p38 mediated apoptosis of neural progenitor cells via the XIAP-Tak1-Tab1 complex. Its effect on NF-kappaB has yet to be explored. Herein we report that NRAGE, via the same XIAP-Tak1-Tab1 complex, is required for the phosphorylation of IKK -alpha/beta and subsequent transcriptional activation of the p65 subunit of NF-kappaB. Ablation of endogenous NRAGE by siRNA inhibited NF-kappaB pathway activation, while ablation of Tak1 and Tab1 by morpholino inhibited overexpression of NRAGE from activating NF-kappaB. Finally, cytokine profiling of an NRAGE over-expressing stable line revealed the expression of macrophage migration inhibitory factor. Modulation of NRAGE expression revealed novel roles in regulating NF-kappaB activity in the non-canonical bone morphogenic protein signaling pathway. The expression of macrophage migration inhibitory factor by bone morphogenic protein -4 reveals novel crosstalk between an immune cytokine and a developmental pathway.

  15. Generation and functional characterization of a BCL10-inhibitory peptide that represses NF-kappaB activation. (United States)

    Marasco, Daniela; Stilo, Romania; Sandomenico, Annamaria; Monti, Simona Maria; Tizzano, Barbara; de Capua, Antonia; Varricchio, Ettore; Liguoro, Domenico; Zotti, Tiziana; Formisano, Silvestro; Ruvo, Menotti; Vito, Pasquale


    The molecular complex containing BCL10 and CARMA [CARD (caspase recruitment domain)-containing MAGUK (membrane-associated guanylate kinase)] proteins has recently been identified as a key component in the signal transduction pathways that regulate activation of the transcription factor NF-kappaB (nuclear factor kappaB) in lymphoid and non-lymphoid cells. Assembly of complexes containing BCL10 and CARMA proteins relies on homophilic interactions established between the CARDs of these proteins. In order to identify BCL10-inhibitory peptides, we have established a method of assaying peptides derived from the CARD of BCL10 in binding competition assays of CARD-CARD self-association. By this procedure, a short peptide corresponding to amino acid residues 91-98 of BCL10 has been selected as an effective inhibitor of protein self-association. When tested in cell assays for its capacity to block NF-kappaB activation, this peptide represses activation of NF-kappaB mediated by BCL10, CARMA3 and PMA/ionomycin stimulation. Collectively, these results indicate that residues 91-98 of BCL10 are involved in BCL10 self-association and also participate in the interaction with external partners. We also show that blocking of the CARD of BCL10 may potentially be used for the treatment of pathological conditions associated with inappropriate NF-kappaB activation.

  16. Minnesota Pheasant Range (United States)

    Minnesota Department of Natural Resources — This dataset delineates the spatial range of wild pheasant populations in Minnesota as of 2002 by dividing the MN state boundary into 2 units: pheasant range and...

  17. Towards optimal range medians

    DEFF Research Database (Denmark)

    Brodal, Gerth Stølting; Gfeller, Beat; Jørgensen, Allan Grønlund


    that in the cell-probe model, any data structure which supports updates in O(logO(1)n) time must have Ω(log n/loglog n) query time. Our approach naturally generalizes to higher-dimensional range median problems, where element positions and query ranges are multidimensional - it reduces a range median query...... to a logarithmic number of range counting queries....

  18. Roles for NF-kappaB and c-Fos in osteoclasts. (United States)

    Boyce, Brendan F; Yamashita, Teruhito; Yao, Zhenqiang; Zhang, Qian; Li, Fang; Xing, Lianping


    NF-kappaB and c-Fos are transcription factors that are activated in immune cells and in most other cell types following stimulation by a variety of factors, including cytokines, growth factors, and hormones. They regulate the expression of a large number of genes, and both are activated in osteoclast precursors after RANKL, IL-1, or TNF bind to their respective receptors. However, of these cytokines, only RANKL is required for the induction of osteoclast formation in vivo. Nevertheless, it is likely that IL-1, TNF, and other cytokines participate in the upregulation of osteoclast formation seen in a variety of conditions that affect the skeleton in which cytokine production is increased, including estrogen deficiency and inflammatory bone diseases. In this review, the RANKL/ OPG/RANK system and roles for NF-kappaB and c-Fos in osteoclasts are reviewed along with our current understanding of how this system may be disrupted in common bone diseases, such as postmenopausal osteoporosis, inflammatory arthritis, and Paget's disease.

  19. Localization of the kappa opioid receptor gene to human chromosome band 8q11. 2

    Energy Technology Data Exchange (ETDEWEB)

    Yasuda, Kazuki; Takeda, Jun; Bell, G.I.; Espinosa, R.; Le Beau, M.M. (Univ. of Chicago, IL (United States))


    Using the cloned mouse kappa opioid receptor cDNA clone as a probe, screened a human genomic library and isolated a clone containing part of the human kappa opioid receptor gene (OPRK1), designated [lambda]hSR4-1. To determine the chromosomal localization of OPRK1, [lambda]hSR4-1 DNA was labeled with biotin by nick-translation in the presence of bio-11-dUTP and hybridized to human metaphase cells prepared from phytohemagglutinin-stimulated peripheral blood lymphocytes as described previously. Hybridization of the OPRK1-specific probe [lambda]hSR4-1 DNA to normal human metaphase chromosomes resulted in specific labeling only of chromosome 8. Specific labeling of 8q11 was observed on all 4 (6 cells), 3 (9 cells), 2 (9 cells), or 1 (1 cell) chromatid of the chromosome 8 homologs in 25 cells examined. Of 72 signals observed, 70 were located at 8q11. 1 signal was located at 7q11 and at 12p11. In most cells, the signal on 8q was located at 8q11.2. 7 refs., 1 fig.

  20. Finite volume effects in pion-kaon scattering and reconstruction of the kappa(800) resonance

    CERN Document Server

    Döring, M


    Simulating the kappa(800) on the lattice is a challenging task that starts to become feasible due to the rapid progress in recent-years lattice QCD calculations. As the resonance is broad, special attention to finite-volume effects has to be paid, because no sharp resonance signal as from avoided level crossing can be expected. In the present article, we investigate the finite volume effects in the framework of unitarized chiral perturbation theory using next-to-leading order terms. After a fit to meson-meson partial wave data, lattice levels for piK scattering are predicted. In addition, levels are shown for the quantum numbers in which the sigma(600), f_0(980), a_0(980), phi(1020), K*(892), and rho(770) appear, as well as the repulsive channels. Methods to extract the kappa(800) signal from the lattice spectrum are presented. Using pseudo-data, we estimate the precision that lattice data should have to allow for a clear-cut extraction of this resonance. To put the results into context, in particular the req...

  1. Trapping of hydrogen in hafnium-based high kappa dielectric thin films for advanced CMOS applications (United States)

    Ukirde, Vaishali

    In recent years, advanced high kappa gate dielectrics are under serious consideration to replace SiO2 and SiON in semiconductor industry. Hafnium-based dielectrics such as hafnium oxides, oxynitrides and Hf-based silicates/nitrided silicates are emerging as some of the most promising alternatives to SiO2/SiON gate dielectrics in complementary metal oxide semiconductor (CMOS) devices. Extensive efforts have been taken to understand the effects of hydrogen impurities in semiconductors and its behavior such as incorporation, diffusion, trapping and release with the aim of controlling and using it to optimize the performance of electronic device structures. In this dissertation, a systematic study of hydrogen trapping and the role of carbon impurities in various alternate gate dielectric candidates, HfO2/Si, HfxSi1-xO2/Si, HfON/Si and HfON(C)/Si is presented. It has been shown that processing of high kappa dielectrics may lead to some crystallization issues. Rutherford backscattering spectroscopy (RBS) for measuring oxygen deficiencies, elastic recoil detection analysis (ERDA) for quantifying hydrogen and nuclear reaction analysis (NRA) for quantifying carbon, X-ray diffraction (XRD) for measuring degree of crystallinity and X-ray photoelectron spectroscopy (XPS) were used to characterize these thin dielectric materials. ERDA data are used to characterize the evolution of hydrogen during annealing in hydrogen ambient in combination with preprocessing in oxygen and nitrogen.

  2. DMPD: TLR signalling and activation of IRFs: revisiting old friends from the NF-kappaBpathway. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16006187 TLR signalling and activation of IRFs: revisiting old friends from the NF-...kappaBpathway. Moynagh PN. Trends Immunol. 2005 Sep;26(9):469-76. (.png) (.svg) (.html) (.csml) Show TLR signalling and activation... of IRFs: revisiting old friends from the NF-kappaBpathway. PubmedID 16006187 Title TLR signalling and activati...on of IRFs: revisiting old friends from the NF-kappaBpat

  3. Tau ranging revisited (United States)

    Tausworthe, R. C.


    It is shown that a ranging receiver with a sufficient and reasonable number of correlators is competitive with the current sequential component ranging system by some 1.5 to 2.5 dB. The optimum transmitter code, the optimum receiver, and a near-maximum-lilelihood range-estimation algorithm are presented.

  4. Valuing hope. (United States)

    McMillan, John; Walker, Simon; Hope, Tony


    This article argues that hope is of value in clinical ethics and that it can be important for clinicians to be sensitive to both the risks of false hope and the importance of retaining hope. However, this sensitivity requires an understanding of the complexity of hope and how it bears on different aspects of a well-functioning doctor-patient relationship. We discuss hopefulness and distinguish it, from three different kinds of hope, or 'hopes for', and then relate these distinctions back to differing accounts of autonomy. This analysis matters because it shows how an overly narrow view of the ethical obligations of a clinician to their patient, and autonomy, might lead to scenarios where patients regret the choices they make.

  5. Bacterial effector binding to ribosomal protein s3 subverts NF-kappaB function.

    Directory of Open Access Journals (Sweden)

    Xiaofei Gao


    Full Text Available Enteric bacterial pathogens cause food borne disease, which constitutes an enormous economic and health burden. Enterohemorrhagic Escherichia coli (EHEC causes a severe bloody diarrhea following transmission to humans through various means, including contaminated beef and vegetable products, water, or through contact with animals. EHEC also causes a potentially fatal kidney disease (hemolytic uremic syndrome for which there is no effective treatment or prophylaxis. EHEC and other enteric pathogens (e.g., enteropathogenic E. coli (EPEC, Salmonella, Shigella, Yersinia utilize a type III secretion system (T3SS to inject virulence proteins (effectors into host cells. While it is known that T3SS effectors subvert host cell function to promote diarrheal disease and bacterial transmission, in many cases, the mechanisms by which these effectors bind to host proteins and disrupt the normal function of intestinal epithelial cells have not been completely characterized. In this study, we present evidence that the E. coli O157:H7 nleH1 and nleH2 genes encode T3SS effectors that bind to the human ribosomal protein S3 (RPS3, a subunit of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB transcriptional complexes. NleH1 and NleH2 co-localized with RPS3 in the cytoplasm, but not in cell nuclei. The N-terminal region of both NleH1 and NleH2 was required for binding to the N-terminus of RPS3. NleH1 and NleH2 are autophosphorylated Ser/Thr protein kinases, but their binding to RPS3 is independent of kinase activity. NleH1, but not NleH2, reduced the nuclear abundance of RPS3 without altering the p50 or p65 NF-kappaB subunits or affecting the phosphorylation state or abundance of the inhibitory NF-kappaB chaperone IkappaBalpha NleH1 repressed the transcription of a RPS3/NF-kappaB-dependent reporter plasmid, but did not inhibit the transcription of RPS3-independent reporters. In contrast, NleH2 stimulated RPS3-dependent transcription, as well

  6. Bacterial effector binding to ribosomal protein s3 subverts NF-kappaB function.

    Directory of Open Access Journals (Sweden)

    Xiaofei Gao


    Full Text Available Enteric bacterial pathogens cause food borne disease, which constitutes an enormous economic and health burden. Enterohemorrhagic Escherichia coli (EHEC causes a severe bloody diarrhea following transmission to humans through various means, including contaminated beef and vegetable products, water, or through contact with animals. EHEC also causes a potentially fatal kidney disease (hemolytic uremic syndrome for which there is no effective treatment or prophylaxis. EHEC and other enteric pathogens (e.g., enteropathogenic E. coli (EPEC, Salmonella, Shigella, Yersinia utilize a type III secretion system (T3SS to inject virulence proteins (effectors into host cells. While it is known that T3SS effectors subvert host cell function to promote diarrheal disease and bacterial transmission, in many cases, the mechanisms by which these effectors bind to host proteins and disrupt the normal function of intestinal epithelial cells have not been completely characterized. In this study, we present evidence that the E. coli O157:H7 nleH1 and nleH2 genes encode T3SS effectors that bind to the human ribosomal protein S3 (RPS3, a subunit of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB transcriptional complexes. NleH1 and NleH2 co-localized with RPS3 in the cytoplasm, but not in cell nuclei. The N-terminal region of both NleH1 and NleH2 was required for binding to the N-terminus of RPS3. NleH1 and NleH2 are autophosphorylated Ser/Thr protein kinases, but their binding to RPS3 is independent of kinase activity. NleH1, but not NleH2, reduced the nuclear abundance of RPS3 without altering the p50 or p65 NF-kappaB subunits or affecting the phosphorylation state or abundance of the inhibitory NF-kappaB chaperone IkappaBalpha NleH1 repressed the transcription of a RPS3/NF-kappaB-dependent reporter plasmid, but did not inhibit the transcription of RPS3-independent reporters. In contrast, NleH2 stimulated RPS3-dependent transcription, as well

  7. Fair Value or Market Value?

    Directory of Open Access Journals (Sweden)

    Bogdan Cosmin Gomoi


    Full Text Available When taking into consideration the issue of defining the “fair value” concept, those less experimented in the area often fall in the “price trap”, which is considered as an equivalent of the fair value of financial structures. This valuation basis appears as a consequence of the trial to provide an “accurate image” by the financial statements and, also, as an opportunity for the premises offered by the activity continuing principle. The specialized literature generates ample controversies regarding the “fair value” concept and the “market value” concept. The paper aims to debate this issue, taking into account various opinions.

  8. The kappa-opioid receptor is involved in the stimulating effect of nicotine on adrenocortical activity but not in nicotine induced anxiety. (United States)

    Marco, Eva Maria; Llorente, Ricardo; Pérez-Alvarez, Laura; Moreno, Enrique; Guaza, Carmen; Viveros, Maria Paz


    The kappa (kappa) opioid system appears to interact with nicotine in the modulation of locomotion and addiction related processes. In this study we have investigated the possible implication of the kappa-opioid system in the effects of nicotine on anxiety and adrenocortical activity. In two different experiments, we analysed the possible interaction between nicotine (0.5 mg/kg i.p.) and either the kappa-opioid receptor antagonist nor-binaltorphimine (5 mg/kg i.p.) or the kappa-opioid receptor agonist U50,488H (1 mg/kg s.c.). Behavioural and endocrine experiments were performed in different groups of animals. Animals were exposed to the holeboard immediately followed by the plus-maze. Serum corticosterone levels were determined by radioimmunoassay. Nicotine induced an anxiogenic-like effect in the plus-maze and a significant decrease of holeboard activity. The anxiogenic-like effect in the plus-maze was not modified by any of the kappa-opioid receptor ligands. Nicotine also induced a significant increase in the corticosterone levels, and the kappa antagonist, which did not exert any effect per se, antagonised this effect. The kappa-agonist U50,488H induced a significant increase in corticosterone concentration when administered alone. We provide the first evidence for the involvement of the kappa-opioid receptor in the stimulatory effect of nicotine on adrenocortical activity.

  9. p38 mitogen-activated protein kinase up-regulates NF-{kappa}B transcriptional activation through RelA phosphorylation during stretch-induced myogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Ji, Guoping [Department of Orthodontics, College of Stomatology, Ninth People' s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Research Institute of Stomatology, Shanghai 200011 (China); Liu, Dongxu [Department of Orthodontics, College of Stomatology, Shandong University, Jinan, Shandong Province 250012 (China); Liu, Jing [Department of Orthodontics, The Affiliated Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong Province 266075 (China); Gao, Hui [Department of Orthodontics, Tianjin Stomatological Hospital, Tianjin 300041 (China); Yuan, Xiao, E-mail: [Department of Orthodontics, The Affiliated Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong Province 266075 (China); Shen, Gang, E-mail: [Department of Orthodontics, College of Stomatology, Ninth People' s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Research Institute of Stomatology, Shanghai 200011 (China)


    p38 MAPK and nuclear factor-B (NF-B) signaling pathways play an indispensable role in the control of skeletal myogenesis. The specific contribution of these signaling pathways to the response of myoblast to the mechanical stimulation and the molecular mechanisms underlying this response remain unresolved. Using an established in vitro model, we now show that p38 MAP kinase activity regulates the transcriptional activation of NF-{kappa}B in response to mechanical stimulation of myoblasts. Furthermore, SB203580 blocked stretch-induced NF-{kappa}B activation during myogenesis, not through down-regulation of degradation of I{kappa}B-{alpha}, and consequent translocation of the p65 subunit of NF-{kappa}B to the nucleus. It is likely that stretch-induced NF-{kappa}B activation by phosphorylation of p65 NF-{kappa}B. Moreover, depletion of p38{alpha} using siRNA significantly reduces stretch-induced phosphorylation of RelA and NF-{kappa}B activity. These results provides the first evidence of a cross-talk between p38 MAPK and NF-{kappa}B signaling pathways during stretch-induced myogenesis, with phosphorylation of RelA being one of the effectors of this promyogenic mechanism. The {alpha} isoform of p38MAP kinase regulates the transcriptional activation of NF-{kappa}B following stimulation with cyclic stretch.

  10. Evaluation of Diagnostic Value in Using a Panel of Multiple Tumor-Associated Antigens for Immunodiagnosis of Cancer

    Directory of Open Access Journals (Sweden)

    Peng Wang


    Full Text Available To determine whether a panel of multiple tumor-associated antigens (TAAs would enhance antibody detection, the diagnostic value of autoantibodies to a panel of multiple TAAs in cancer has been evaluated. The TAAs used in this study was composed of eight TAAs including Imp1, p62, Koc, p53, C-myc, Cyclin B1, Survivin, and p16 full-length recombinant proteins. Enzyme-linked immunosorbent assay and immunoblotting were used to detect antibodies in 304 cancer sera and also 58 sera from normal individuals. The antibody frequency to any individual TAA in cancer was variable but rarely exceeded 20%. With the successive addition of TAAs to a final combination of total of eight antigens, there was a stepwise increase of positive antibody reactions reaching a sensitivity of 63.5% and a specificity of 86.2% in the combined cancer group. In different types of cancer, the ranges of positive and negative likelihood ratio were 4.07–4.76 and 0.39–0.51, respectively, and the ranges of positive and negative predictive values were 74.2–88.7% and 58.8–75.8%, respectively. Agreement rate and Kappa value were 67.1% and 0.51, respectively. These results further support our previous hypothesis that detection of anti-TAAs autoantibodies for diagnosis of certain type of cancer can be enhanced by using a miniarray of several TAAs.

  11. Relative Timing Between Kappa Opioid Receptor Activation and Cocaine Determines the Impact on Reward and Dopamine Release (United States)

    Chartoff, Elena H; Ebner, Shayla R; Sparrow, Angela; Potter, David; Baker, Phillip M; Ragozzino, Michael E; Roitman, Mitchell F


    Negative affective states can increase the rewarding value of drugs of abuse and promote drug taking. Chronic cocaine exposure increases levels of the neuropeptide dynorphin, an endogenous ligand at kappa opioid receptors (KOR) that suppresses dopamine release in the nucleus accumbens (NAc) and elicits negative affective states upon drug withdrawal. However, there is evidence that the effects of KOR activation on affective state are biphasic: immediate aversive effects are followed by delayed increases in reward. The impact of KOR-induced affective states on reward-related effects of cocaine over time is not known. We hypothesize that the initial aversive effects of KOR activation increase, whereas the delayed rewarding effects decrease, the net effects of cocaine on reward and dopamine release. We treated rats with cocaine at various times (15 min to 48 h) after administration of the selective KOR agonist salvinorin A (salvA). Using intracranial self-stimulation and fast scan cyclic voltammetry, we found that cocaine-induced increases in brain stimulation reward and evoked dopamine release in the NAc core were potentiated when cocaine was administered within 1 h of salvA, but attenuated when administered 24 h after salvA. Quantitative real-time PCR was used to show that KOR and prodynorphin mRNA levels were decreased in the NAc, whereas tyrosine hydroxylase and dopamine transporter mRNA levels and tissue dopamine content were increased in the ventral tegmental area 24 h post-salvA. These findings raise the possibility that KOR activation—as occurs upon withdrawal from chronic cocaine—modulates vulnerability to cocaine in a time-dependent manner. PMID:26239494

  12. Yang-Baxter sigma models and Lax pairs arising from $\\kappa$-Poincar\\'e $r$-matrices

    CERN Document Server

    Borowiec, Andrzej; Lukierski, Jerzy; Sakamoto, Jun-ichi; Yoshida, Kentaroh


    We study Yang-Baxter sigma models with deformed 4D Minkowski spacetimes arising from classical $r$-matrices associated with $\\kappa$-deformations of the Poincar\\'e algebra. These classical $\\kappa$-Poincar\\'e $r$-matrices describe three kinds of deformations: 1) the standard deformation, 2) the tachyonic deformation, and 3) the light-cone deformation. For each deformation, the metric and two-form $B$-field are computed from the associated $r$-matrix. The first two deformations, related to the modified classical Yang-Baxter equation, lead to T-duals of dS$_4$ and AdS$_4$\\,, respectively. The third deformation, associated with the homogeneous classical Yang-Baxter equation, leads to a time-dependent pp-wave background. Finally, we construct a Lax pair for the generalized $\\kappa$-Poincar\\'e $r$-matrix that unifies the three kinds of deformations mentioned above as special cases.

  13. Measuring nebular temperatures: the effect of new collision strengths with equilibrium and kappa-distributed electron energies

    CERN Document Server

    Nicholls, David C; Sutherland, Ralph S; Kewley, Lisa J; Palay, Ethan


    In this paper we develop tools for observers to use when analysing nebular spectra for temperatures and metallicities, with two goals: to present a new, simple method to calculate equilibrium electron temperatures for collisionally excited line flux ratios, using the latest atomic data; and to adapt current methods to include the effects of possible non-equilibrium '{\\kappa}' electron energy distributions. Adopting recent collision strength data for [O iii], [S iii], [O ii], [S ii], and [N ii], we find that existing methods based on older atomic data seriously overestimate the electron temperatures, even when considering purely Maxwellian statistics. If {\\kappa} distributions exist in H ii regions and planetary nebulae as they do in solar system plasmas, it is important to investigate the observational consequences. This paper continues our previous work on the {\\kappa} distribution (Nicholls et al. 2012). We present simple formulaic methods that allow observers to (a) measure equilibrium electron temperature...

  14. Highly condensed fluorinated methacrylate hybrid material for transparent low-kappa passivation layer in LCD-TFT. (United States)

    Oh, Ji-Hoon; Kwak, Seung-Yeon; Yang, Seung-Cheol; Bae, Byeong-Soo


    Photocurable and highly condensed fluorinated methacrylate oligosiloxane, with a low dielectric constant (kappa = 2.54), was prepared by a nonhydrolytic sol-gel condensation reaction. The oligosiloxane resin was then spin-coated, photocured, and thermally baked in order to fabricate a fluorinated methacrylate hybrid material (FM hybrimer) thin film. This study investigated the application of this FM hybrimer film as a low-kappa passivation layer in LCD-based thin film transistors (TFT). It was found that a dielectric constant as low as kappa = 2.54 could be obtained, without introducing pores in the dense FM hybrimer films. This study compares FM hybrimer film characteristics with those required for passivation layers in LCD-TFTs, including thermal stability, optical transmittance, hydrophobicity, gap fill, and planarization effects as well as electrical insulation.

  15. Role of magnetic field fluctuations in the Evolution of the kappa Distribution Functions in the Plasma Sheet (United States)

    Espinoza, Cristobal; Antonova, Elizaveta; Stepanova, Marina; Valdivia, Juan Alejandro


    The evolution with the distance to Earth of ion and electron distribution functions in the plasma sheet, approximated by kappa distributions, was studied by Stepanova and Antonova (2015, JGRA 120). Using THEMIS data for 5 events of satellite alignments along the tail, covering between 5 and 30 Earth radii, they found that the kappa parameter increases tailwards, for both ions and electrons. In this work we analyse the magnetic fluctuations present in THEMIS data for the same 5 events. The aim is to explore the hypothesis proposed by Navarro et al. (2014, PRL 112), for solar wind plasmas, that the observed magnetic fluctuations could be closely related to spontaneous fluctuations in the plasma, if this can be described by stable distributions. Here we present our first results on the correlation between the spectral properties of the magnetic fluctuations and the observed parameters of the kappa distributions for different distances from Earth.

  16. Inhibition of NF-kappaB activation and expression of inflammatory mediators by polyacetylene spiroketals from Plagius flosculosus. (United States)

    Calzado, Marco A; Lüdi, Katharina Schmid; Fiebich, Bernd; Ben-Neriah, Yinon; Bacher, Susanne; Munoz, Eduardo; Ballero, Mauro; Prosperini, Simona; Appendino, Giovanni; Schmitz, M Lienhard


    Transcription factor NF-kappaB plays a key role for the inducible expression of genes mediating proinflammatory effects and is thus an important target for the development of antiinflammatory drugs. Here, we show that extracts from the plant Plagius flosculosus (L.) Alavi and Heyw. can inhibit the induction of NF-kappaB activity, and we describe the identification of three spiroketal compounds. Of those, only compound 1 could inhibit the phosphorylation and proteasomal degradation of IkappaB, thus preventing the nuclear import and DNA binding of NF-kappaB. Accordingly, compound 1, which is also found in the widely used medicinal herb chamomile, interfered with the LPS-induced production of IL-1, IL-6, TNF, and PGE2 in primary human monocytes.

  17. Phylogeny, genomic organization and expression of lambda and kappa immunoglobulin light chain genes in a reptile, Anolis carolinensis. (United States)

    Wu, Qian; Wei, Zhiguo; Yang, Zhi; Wang, Tao; Ren, Liming; Hu, Xiaoxiang; Meng, Qingyong; Guo, Ying; Zhu, Qinghong; Robert, Jacques; Hammarström, Lennart; Li, Ning; Zhao, Yaofeng


    The reptiles are the last major taxon of jawed vertebrates in which immunoglobulin light chain isotypes have not been well characterized. Using the recently released genome sequencing data, we show in this study that the reptile Anolis carolinensis expresses both lambda and kappa light chain genes. The genomic organization of both gene loci is structurally similar to their respective counterparts in mammals. The identified lambda locus contains three constant region genes each preceded by a joining gene segment, and a total of 37 variable gene segments. In contrast, the kappa locus contains only a single constant region gene, and two joining gene segments with a single family of 14 variable gene segments located upstream. Analysis of junctions of the recombined VJ transcripts reveals a paucity of N and P nucleotides in both expressed lambda and kappa sequences. These results help us to understand the generation of the immunoglobulin repertoire in reptiles and immunoglobulin evolution in vertebrates.

  18. Rearrangement of mouse immunoglobulin kappa deleting element recombining sequence promotes immune tolerance and lambda B cell production. (United States)

    Vela, José Luis; Aït-Azzouzene, Djemel; Duong, Bao Hoa; Ota, Takayuki; Nemazee, David


    The recombining sequence (RS) of mouse and its human equivalent, the immunoglobulin (Ig) kappa deleting element (IGKDE), are sequences found at the 3' end of the Ig kappa locus (Igk) that rearrange to inactivate Igk in developing B cells. RS recombination correlates with Ig lambda (Iglambda) light (L) chain expression and likely plays a role in receptor editing by eliminating Igk genes encoding autoantibodies. A mouse strain was generated in which the recombination signal of RS was removed, blocking RS-mediated Igk inactivation. In RS mutant mice, receptor editing and self-tolerance were impaired, in some cases leading to autoantibody formation. Surprisingly, mutant mice also made fewer B cells expressing lambda chain, whereas lambda versus kappa isotype exclusion was only modestly affected. These results provide insight into the mechanism of L chain isotype exclusion and indicate that RS has a physiological role in promoting the formation of lambda L chain-expressing B cells.

  19. Valuing vaccination (United States)

    Bärnighausen, Till; Bloom, David E.; Cafiero-Fonseca, Elizabeth T.; O’Brien, Jennifer Carroll


    Vaccination has led to remarkable health gains over the last century. However, large coverage gaps remain, which will require significant financial resources and political will to address. In recent years, a compelling line of inquiry has established the economic benefits of health, at both the individual and aggregate levels. Most existing economic evaluations of particular health interventions fail to account for this new research, leading to potentially sizable undervaluation of those interventions. In line with this new research, we set forth a framework for conceptualizing the full benefits of vaccination, including avoided medical care costs, outcome-related productivity gains, behavior-related productivity gains, community health externalities, community economic externalities, and the value of risk reduction and pure health gains. We also review literature highlighting the magnitude of these sources of benefit for different vaccinations. Finally, we outline the steps that need to be taken to implement a broad-approach economic evaluation and discuss the implications of this work for research, policy, and resource allocation for vaccine development and delivery. PMID:25136129

  20. Human psychopharmacology and dose-effects of salvinorin A, a kappa opioid agonist hallucinogen present in the plant Salvia divinorum. (United States)

    Johnson, Matthew W; MacLean, Katherine A; Reissig, Chad J; Prisinzano, Thomas E; Griffiths, Roland R


    Salvinorin A is a potent, selective nonnitrogenous kappa opioid agonist and the known psychoactive constituent of Salvia divinorum, a member of the mint family that has been used for centuries by Mazatec shamans of Mexico for divination and spiritual healing. S. divinorum has over the last several years gained increased popularity as a recreational drug. This is a double-blind, placebo controlled study of salvinorin A in 4 psychologically and physically healthy hallucinogen-using adults. Across sessions, participants inhaled 16 ascending doses of salvinorin A and 4 intermixed placebo doses under comfortable and supportive conditions. Doses ranged from 0.375 μg/kg to 21 μg/kg. Subject-rated drug strength was assessed every 2 min for 60 min after inhalation. Orderly time- and dose-related effects were observed. Drug strength ratings peaked at 2 min (first time point) and definite subjective effects were no longer present at approximately 20 min after inhalation. Dose-related increases were observed on questionnaire measures of mystical-type experience (Mysticism Scale) and subjective effects associated with classic serotonergic (5-HT2(A)) hallucinogens (Hallucinogen Rating Scale). Salvinorin A did not significantly increase heart rate or blood pressure. Participant narratives indicated intense experiences characterized by disruptions in vestibular and interoceptive signals (e.g., change in spatial orientation, pressure on the body) and unusual and sometimes recurring themes across sessions such as revisiting childhood memories, cartoon-like imagery, and contact with entities. Under these prepared and supportive conditions, salvinorin A occasioned a unique profile of subjective effects having similarities to classic hallucinogens, including mystical-type effects.

  1. 大kappa角成因的分析%The analysis of the cause of big kappa angle

    Institute of Scientific and Technical Information of China (English)

    卢秀珍; 毕宏生; 潘雪梅; 王桂敏; 袁明俊


    Objective To study the cause of the big kappa angle.Methods Twenty-seven eyes were measured with kappa angle, central corneal thickness, white-to-white corneal horizontal diameter, and the optic disc-macular distance.Results The mean kappa angle of the abnormal big kappa eyes was 9.48±2.24°, the optic dise-macular distance was 5.08±1.33mm, mean central corneal thickness was 580.58±53.01 um, mean corneal horizontal diameter was 12.13±0.51mm, Which were bigger than the normal eyes.Conclusions Several abnormal structural factors are found in the big kappa angle eyes, which maybe the cause of the big kappa angles.%目的 对大kappa角患者进行多处数据分析,发现其异常之处,探讨大kappa角形成的原因.方法 测量异常大kappa角眼的kappa角、中央角膜厚度及角膜横径,眼轴,眼底照像并测量视盘-黄斑间距.结果 与对侧正常眼比较,大kappa角患眼视盘-黄斑间距增大.均值为5.084mm;其中央角膜厚度平均值为580.58μm以及角膜横径平均值为12.13mm,均大于正常眼;眼轴与正常眼相似.结论 大kappa角患眼存在多处结构发育异常,可能是造成这一异常外观的成因.

  2. 1,25-dihydroxyvitamin D{sub 3} impairs NF-{kappa}B activation in human naive B cells

    Energy Technology Data Exchange (ETDEWEB)

    Geldmeyer-Hilt, Kerstin, E-mail: [Allergie-Centrum-Charite, CCM, Klinik fuer Dermatologie und Allergologie, Charite - Universitaetsmedizin Berlin, Chariteplatz 1, 10117 Berlin (Germany); Heine, Guido, E-mail: [Allergie-Centrum-Charite, CCM, Klinik fuer Dermatologie und Allergologie, Charite - Universitaetsmedizin Berlin, Chariteplatz 1, 10117 Berlin (Germany); Deutsches Rheuma-Forschungszentrum Berlin, Chariteplatz 1, 10117 Berlin (Germany); Hartmann, Bjoern, E-mail: [Allergie-Centrum-Charite, CCM, Klinik fuer Dermatologie und Allergologie, Charite - Universitaetsmedizin Berlin, Chariteplatz 1, 10117 Berlin (Germany); Baumgrass, Ria, E-mail: [Deutsches Rheuma-Forschungszentrum Berlin, Chariteplatz 1, 10117 Berlin (Germany); Radbruch, Andreas, E-mail: [Deutsches Rheuma-Forschungszentrum Berlin, Chariteplatz 1, 10117 Berlin (Germany); Worm, Margitta, E-mail: [Allergie-Centrum-Charite, CCM, Klinik fuer Dermatologie und Allergologie, Charite - Universitaetsmedizin Berlin, Chariteplatz 1, 10117 Berlin (Germany)


    Highlights: {yields} In naive B cells, VDR activation by calcitriol results in reduced NF-{kappa}B p105 and p50 protein expression. {yields} Ligating the VDR with calcitriol causes reduced nuclear translocation of NF-{kappa}B p65. {yields} Reduced nuclear amount of p65 after calcitriol incubation results in reduced binding of p65 on the p105 promoter. {yields} Thus, vitamin D receptor signaling may reduce or prevent activation of B cells and unwanted immune responses, e.g. in IgE dependent diseases such as allergic asthma. -- Abstract: 1{alpha},25-dihydroxyvitamin D{sub 3} (calcitriol), the bioactive metabolite of vitamin D, modulates the activation and inhibits IgE production of anti-CD40 and IL-4 stimulated human peripheral B cells. Engagement of CD40 results in NF-{kappa}B p50 activation, which is essential for the class switch to IgE. Herein, we investigated by which mechanism calcitriol modulates NF-{kappa}B mediated activation of human naive B cells. Naive B cells were predominantly targeted by calcitriol in comparison with memory B cells as shown by pronounced induction of the VDR target gene cyp24a1. Vitamin D receptor activation resulted in a strongly reduced p105/p50 protein and mRNA expression in human naive B cells. This effect is mediated by impaired nuclear translocation of p65 and consequently reduced binding of p65 to its binding site in the p105 promoter. Our data indicate that the vitamin D receptor reduces NF-{kappa}B activation by interference with NF-{kappa}B p65 and p105. Thus, the vitamin D receptor inhibits costimulatory signal transduction in naive B cells, namely by reducing CD40 signaling.

  3. Cirhin up-regulates a canonical NF-{kappa}B element through strong interaction with Cirip/HIVEP1

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Bin; Mitchell, Grant A. [Genetique Medicale, Centre de Recherche CHU Sainte-Justine, Departement de Pediatrie, Universite de Montreal, Montreal, QC (Canada); Richter, Andrea, E-mail: [Genetique Medicale, Centre de Recherche CHU Sainte-Justine, Departement de Pediatrie, Universite de Montreal, Montreal, QC (Canada)


    North American Indian childhood cirrhosis (NAIC/CIRH1A) is a severe autosomal recessive intrahepatic cholestasis. All NAIC patients have a homozygous mutation in CIRH1A that changes conserved Arg565 to Trp (R565W) in Cirhin, a nucleolar protein of unknown function. Subcellular localization is unaffected by the mutation. Yeast two-hybrid screening identified Cirip (Cirhin interaction protein) and found that interaction between Cirip and R565W-Cirhin was weakened. Co-immunoprecipitation of the two proteins from nuclear extracts of HeLa cells strongly supports the yeast two hybrid results. Cirip has essentially the same sequence as the C-terminal of HIVEP1, a regulator of a canonical NF-{kappa}B sequence. Since Cirip has the zinc fingers required for this interaction, we developed an in vitro assay based on this element in mammalian cells to demonstrate functional Cirhin-Cirip interaction. The strong positive effect of Cirip on the NF-{kappa}B sequence was further increased by both Cirhin and R565W-Cirhin. Importantly, the effect of R565W-Cirhin was weaker than that of the wild type protein. We observed increased levels of Cirhin-Cirip complex in nuclear extracts in the presence of this NF-{kappa}B sequence. Our hypothesis is that Cirhin is a transcriptional regulatory factor of this NF-{kappa}B sequence and could be a participant in the regulation of other genes with NF-{kappa}B responsive elements. Since the activities of genes regulated through NF-{kappa}B responsive elements are especially important during development, this interaction may be a key to explain the perinatal appearance of NAIC.

  4. Substring Range Reporting

    DEFF Research Database (Denmark)

    Bille, Philip; Gørtz, Inge Li


    We revisit various string indexing problems with range reporting features, namely, position-restricted substring searching, indexing substrings with gaps, and indexing substrings with intervals. We obtain the following main results. – We give efficient reductions for each of the above problems...... to a new problem, which we call substring range reporting. Hence, we unify the previous work by showing that we may restrict our attention to a single problem rather than studying each of the above problems individually. – We show how to solve substring range reporting with optimal query time and little...... range reporting are based on a novel combination of suffix trees and range reporting data structures. The reductions are simple and general and may apply to other combinations of string indexing with range reporting....

  5. Quince (Cydonia oblonga Miller) peel polyphenols modulate LPS-induced inflammation in human THP-1-derived macrophages through NF-{kappa}B, p38MAPK and Akt inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Essafi-Benkhadir, Khadija [Laboratoire d' epidemiologie Moleculaire et Pathologie Experimentale Appliquee Aux Maladies Infectieuses, Institut Pasteur de Tunis (Tunisia); Refai, Amira [Laboratoire de Recherche sur la Transmission, le Controle et l' immunobiologie des Infections, Institut Pasteur de Tunis (Tunisia); Riahi, Ichrak [Laboratoire d' epidemiologie Moleculaire et Pathologie Experimentale Appliquee Aux Maladies Infectieuses, Institut Pasteur de Tunis (Tunisia); Fattouch, Sami [Laboratory LIP-MB National Institute of Applied Sciences and Technology, Tunis (Tunisia); Karoui, Habib [Laboratoire d' epidemiologie Moleculaire et Pathologie Experimentale Appliquee Aux Maladies Infectieuses, Institut Pasteur de Tunis (Tunisia); Essafi, Makram, E-mail: [Laboratoire de Recherche sur la Transmission, le Controle et l' immunobiologie des Infections, Institut Pasteur de Tunis (Tunisia)


    Highlights: Black-Right-Pointing-Pointer Quince peel polyphenols inhibit LPS-induced secretion of TNF-{alpha} and IL-8. Black-Right-Pointing-Pointer Quince peel polyphenols augment LPS-induced secretion of IL-10 and IL-6. Black-Right-Pointing-Pointer Quince peel polyphenols-mediated inhibition of LPS-induced secretion of TNF-{alpha} is partially mediated by IL-6. Black-Right-Pointing-Pointer The anti-inflammatory effects of quince polyphenols pass through NF-{kappa}B, p38MAPK and Akt inhibition. -- Abstract: Chronic inflammation is a hallmark of several pathologies, such as rheumatoid arthritis, gastritis, inflammatory bowel disease, atherosclerosis and cancer. A wide range of anti-inflammatory chemicals have been used to treat such diseases while presenting high toxicity and numerous side effects. Here, we report the anti-inflammatory effect of a non-toxic, cost-effective natural agent, polyphenolic extract from the Tunisian quince Cydonia oblonga Miller. Lipopolysaccharide (LPS) treatment of human THP-1-derived macrophages induced the secretion of high levels of the pro-inflammatory cytokine TNF-{alpha} and the chemokine IL-8, which was inhibited by quince peel polyphenolic extract in a dose-dependent manner. Concomitantly, quince polyphenols enhanced the level of the anti-inflammatory cytokine IL-10 secreted by LPS-treated macrophages. We further demonstrated that the unexpected increase in IL-6 secretion that occurred when quince polyphenols were associated with LPS treatment was partially responsible for the polyphenols-mediated inhibition of TNF-{alpha} secretion. Biochemical analysis showed that quince polyphenols extract inhibited the LPS-mediated activation of three major cellular pro-inflammatory effectors, nuclear factor-kappa B (NF-{kappa}B), p38MAPK and Akt. Overall, our data indicate that quince peel polyphenolic extract induces a potent anti-inflammatory effect that may prove useful for the treatment of inflammatory diseases and that a quince

  6. Central Makran Range, Pakistan (United States)


    A spectacular view of the Makran Range of Pakistan (27.0N, 65.5E) looking north with the Arabian Sea and the city of Karachi in the foreground. In the center, the Indian sub-continent moving slowly north into the Asian continent has caused the folded sedimentary Makran Range to bend from east-west to north-south as well as the uplift forming The Great Himalaya Range and the high Tibetan Plateau to the north.

  7. Frequent lambda light chain gene rearrangement and expression in a Ly-1 B lymphoma with a productive kappa chain allele.


    Hardy, R R; Dangl, J L; Hayakawa, K.; Jager, G.; Herzenberg, L.A.


    We describe here a murine Ly-1-bearing pre-B-cell tumor that, when induced for kappa light chain expression with bacterial lipopolysaccharide, also gives rise spontaneously to a few percent of cells expressing surface lambda light chains. These lambda-positive cells have undergone DNA rearrangements involving either V lambda 1 or V lambda 2 genes. Nearly all clones of lambda-bearing cells express mu and lambda on their surface (but not kappa). However, all these lambda-positive clones continu...

  8. Programmable oligomers targeting 5'-GGGG-3' in the minor groove of DNA and NF-kappaB binding inhibition. (United States)

    Chenoweth, David M; Poposki, Julie A; Marques, Michael A; Dervan, Peter B


    A series of hairpin oligomers containing benzimidazole (Bi) and imidazopyridine (Ip) rings were synthesized and screened to target 5'-WGGGGW-3', a core sequence in the DNA-binding site of NF-kappaB, a prolific transcription factor important in biology and disease. Five Bi and Ip containing oligomers bound to the 5'-WGGGGW-3' site with high affinity. One of the oligomers (Im-Im-Im-Im-gamma-Py-Bi-Py-Bi-beta-Dp) was able to inhibit DNA binding by the transcription factor NF-kappaB.

  9. Baculovirus Host-Range

    Institute of Scientific and Technical Information of China (English)

    Suzanne M. Thiem; Xiao-Wen Cheng


    Baculoviruses are used as microbial insecticides, protein expression vectors, epitope display platforms, and most recently as vectors for gene therapy. Understanding the mechanisms that control baculovirus host-range and tissue tropisms are important for assessing their safety and for improving their properties for these biotechnology applications. In the past two decades some progress has been made and several baculovirus genes that influence host-range have been identified. Despite this progress, our understanding of the underlying mechanisms that restrict baculovirus host-range is still limited. Here we review what is currently known about baculovirus genes that influence virus host-range.

  10. Compact Antenna Range (United States)

    Federal Laboratory Consortium — Facility consists of a folded compact antenna range including a computer controlled three axis position table, parabolic reflector and RF sources for the measurement...

  11. Laser Range Sensors

    Directory of Open Access Journals (Sweden)

    K.C. Bahuguna


    Full Text Available This paper presents the design aspects of laser range finders and proximity sensors being developed at IRDE for different applications. The principle used in most of the laser range finders is pulse echo or time-of-flight measurement. Optical triangulation is used in proximity sensors while techniques like phase detection and interferometry are employed in instruments for surveying and motion controllers where high accuracy is desired. Most of the laser range finders are designed for ranging non-cooperative targets.

  12. Dryden Aeronautical Test Range (United States)

    Federal Laboratory Consortium — Recently redesignated to honor Dr. Hugh L. Dryden, NASA's Dryden Aeronautical Test Range (DATR) supports aerospace flight research and technology integration, space...

  13. Compact Antenna Range (United States)

    Federal Laboratory Consortium — Facility consists of a folded compact antenna range including a computer controlled three axis position table, parabolic reflector and RF sources for the measurement...

  14. Locus coeruleus kappa-opioid receptors modulate reinstatement of cocaine place preference through a noradrenergic mechanism.