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

Energy Technology Data Exchange (ETDEWEB)

Hong, Hey-Young; Choi, Jiyeon [Department of Biochemistry, College of Natural Sciences, Kangwon National University, 192-1 Hyoja-2-dong, Chuncheon 200-701 (Korea, Republic of); Cho, Young-Wook [Korea Basic Science Institute, Chuncheon Center, Gangwondaehak-gil 1, Chuncheon 200-701 (Korea, Republic of); Kim, Byung-Chul, E-mail: bckim@kangwon.ac.kr [Department of Biochemistry, College of Natural Sciences, Kangwon National University, 192-1 Hyoja-2-dong, Chuncheon 200-701 (Korea, Republic of)

2012-04-06

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

The disagreeable behaviour of the kappa statistic.

Science.gov (United States)

Flight, Laura; Julious, Steven A

2015-01-01

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

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

Science.gov (United States)

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

2004-09-15

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

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.

1990-09-01

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

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

International Nuclear Information System (INIS)

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

1990-01-01

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

{kappa}-deformed realization of D=4 conformal algebra

Energy Technology Data Exchange (ETDEWEB)

Klimek, M. [Technical Univ. of Czestochowa, Inst. of Mathematics and Computer Science, Czestochowa (Poland); Lukierski, J. [Universite de Geneve, Department de Physique Theorique, Geneve (Switzerland)

1995-07-01

We describe the generators of {kappa}-conformal transformations, leaving invariant the {kappa}-deformed d`Alembert equation. In such a way one obtains the conformal extension of-shell spin spin zero realization of {kappa}-deformed Poincare algebra. Finally the algebraic structure of {kappa}-deformed conformal algebra is discussed. (author). 23 refs.

Angle Kappa and its importance in refractive surgery

Directory of Open Access Journals (Sweden)

Majid Moshirfar

2013-01-01

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

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

Science.gov (United States)

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

2016-12-01

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

NF-kappaB in Lung Tumorigenesis

International Nuclear Information System (INIS)

Cai, Zhenjian; Tchou-Wong, Kam-Meng; Rom, William N.

2011-01-01

The development of lung cancer in humans can be divided into three steps initiation, promotion and progression. This process is driven by alterations in related signal transduction pathways. These pathways signal the aberrant activation of NF-kappaB, a transcription factor that regulates the expression of genes important for lung tumorigenesis. Our current knowledge about the role of the NF-kappaB signaling pathway in the development of lung cancer has been bolstered by animal models demonstrating the connection between K-ras and tobacco induced lung transformation with NF-kappaB. Activation of downstream genes leads to cell proliferation, inhibition of apoptosis, angiogenesis, inflammation, invasion, and metastasis

NF-kappaB in Lung Tumorigenesis

Energy Technology Data Exchange (ETDEWEB)

Cai, Zhenjian [Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, New York University School of Medicine, 462 First Avenue, NBV 7N24, New York, NY 10016 (United States); Tchou-Wong, Kam-Meng; Rom, William N., E-mail: william.rom@nyumc.org [Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, New York University School of Medicine, 462 First Avenue, NBV 7N24, New York, NY 10016 (United States); Department of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987 (United States)

2011-12-14

The development of lung cancer in humans can be divided into three steps initiation, promotion and progression. This process is driven by alterations in related signal transduction pathways. These pathways signal the aberrant activation of NF-kappaB, a transcription factor that regulates the expression of genes important for lung tumorigenesis. Our current knowledge about the role of the NF-kappaB signaling pathway in the development of lung cancer has been bolstered by animal models demonstrating the connection between K-ras and tobacco induced lung transformation with NF-kappaB. Activation of downstream genes leads to cell proliferation, inhibition of apoptosis, angiogenesis, inflammation, invasion, and metastasis.

The diagnostic value of indirect lower limb CT venography in the lower extremity deep venous thrombosis

International Nuclear Information System (INIS)

Zhu Li; Guo Youmin; Wang Jianguo; Guo Xiaojuan; Liu Min; Guo Yulin

2009-01-01

Objective: To evaluate indirect CT venography (CTV) in the diagnosis of deep venous thrombosis (DVT). Methods: A total of 516 acute pulmonary embolism patients proved by objective test were analyzed retrospectively. Using the results of lower limb compression sonography as reference standard, the sensitivity, specificity, positive predictive value and negative predictive value of indirect CTV were calculated. The agreement between lower extremity venous sonography and indirect CTV were assessed by Kappa analysis. Results: Among 516 patients with acute pulmonary thromboembolism (PTE), 110 patients underwent both CTV and CTPA and lower extremity sonography. DVT were detected by CTV and sonography simultaneously in 48 patients, while no DVT was detected in 39 patients by both examinations. Thirteen patients were diagnosed to have DVT by CTV without sonography detection, and DVT was detected in other 10 patients only by sonography. The sensitivity, specificity, positive predictive value and negative predictive value of indirect CTV was 82.8% (48/58), 75.0% (39/52), 78.7% (48/61) and 79.6% (39/49). The agreement between lower extremity venous sonography and indirect CTV was good for femoropopliteal vein (Kappa value range from 0.874 to 0.914, P=0.000). Thrombi detected by CTV were 62 and 52 respectively, and for sonography were 67 and 51 respectively. For calf veins, the agreement decreased (Kappa value range from 0.464 to 0.584, P=0.000). Thrombi detected by CTV were 6, 25 and 13 respectively, and for sonography were 13, 38 and 19 respectively. The agreement for external iliac vein was poor (Kappa value range from 0.230 to 0.262, P=0.067 and 0.004, respectively). Thrombi detected by CTV were 33, and for sonography were 17. Conclusions: The indirect CTV has high accuracy in the diagnosis of DVT. Combined CTPA and CTV can image pulmonary arteries and lower extremity veins in one examination. Indirect CTV can reveal thrombus in large pelvic veins, which has an advantage

Ion acoustic solitons in a plasma with two-temperature kappa-distributed electrons

International Nuclear Information System (INIS)

Baluku, T. K.; Hellberg, M. A.

2012-01-01

Existence domains and characteristics of ion acoustic solitons are studied in a two-temperature electron plasma with both electron components being kappa-distributed, as found in Saturn's magnetosphere. As is the case for double-Boltzmann electrons, solitons of both polarities can exist over restricted ranges of fractional hot electron density ratio for this plasma model. Low κ values, which indicate increased suprathermal particles in the tail of the distribution, yield a smaller domain in the parameter space of hot density fraction and normalized soliton velocity (f, M), over which both soliton polarities are supported for a given plasma composition (the coexistence region). For some density ratios that support coexistence, solitons occur even at the lowest (critical) Mach number (i.e., at the acoustic speed), as found recently for a number of other plasma models. Like Maxwellians, low-κ distributions also support positive potential double layers over a narrow range of low fractional cool electron density (<10%).

Measurement of Angle Kappa Using Ultrasound Biomicroscopy and Corneal Topography.

Science.gov (United States)

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

2017-06-01

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

Scalar field propagation in the phi^4 kappa-Minkowski model

OpenAIRE

Meljanac, S.; Samsarov, A.; Trampetic, J.; Wohlgenannt, M.

2011-01-01

In this article we use the noncommutative (NC) kappa-Minkowski phi^4 model based on the kappa-deformed star product, ({*}_h). The action is modified by expanding up to linear order in the kappa-deformation parameter a, producing an effective model on commutative spacetime. For the computation of the tadpole diagram contributions to the scalar field propagation/self-energy, we anticipate that statistics on the kappa-Minkowski is specifically kappa-deformed. Thus our prescription in fact repres...

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

Science.gov (United States)

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

2010-02-01

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

Nonequilibrium approach regarding metals from a linearised kappa distribution

Science.gov (United States)

Domenech-Garret, J. L.

2017-10-01

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

Nonplanar ion acoustic waves with kappa-distributed electrons

International Nuclear Information System (INIS)

Sahu, Biswajit

2011-01-01

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

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

Science.gov (United States)

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

2001-09-01

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

Colorectal cancer: can nutrients modulate NF-kappaB and apoptosis?

Science.gov (United States)

Ravasco, Paula; Aranha, Márcia M; Borralho, Pedro M; Moreira da Silva, Isabel B; Correia, Luís; Fernandes, Afonso; Rodrigues, Cecília M P; Camilo, Maria

2010-02-01

NF-kappaB may promote carcinogenesis by altering cell cycle, inflammatory responses and apoptosis-related gene expression, though cell mechanisms relating diet and colorectal cancer (CRC) remain unveiled in humans. This study in patients with CRC aimed to explore potential interactions between the dietary pattern, nutrient intake, expression of NF-kappaB, apoptosis and tumour histological aggressiveness. Usual diet was assessed by diet history; nutrient composition was determined by DIETPLAN software. Histologically classified patient tissue samples (adenoma, adenocarcinoma and normal surrounding mucosa) were obtained via biopsies during colonoscopy (n=16) or surgery (n=8). NF-kappaB expression was determined by immunohistochemistry and apoptosis by TUNEL assay. NF-kappaB expression and apoptosis were higher in tumours (p<0.01), greater along with histological aggressiveness (p<0.01). Highest intake terciles of animal protein, refined carbohydrates, saturated fat, n-6 fatty acids and alcohol were associated with higher NF-kappaB, apoptosis and histological aggressiveness (p<0.01); the opposite tissue characteristics were associated with highest intake terciles of n-3 fatty acids, fibre, vitamin E, flavonoids, isoflavones, beta-carotene and selenium (p<0.002). Additionally, higher n-6:n-3 fatty acids ratio (median 26:1) was associated with higher NF-kappaB (p<0.006) and apoptosis (p<0.01), and more aggressive histology (p<0.01). Conversely, lower n-6:n-3 fatty acids ratio (median 6:1) was associated with lower NF-kappaB (p<0.002) and apoptosis (p<0.002), and less aggressive histology (p<0.002). NF-kappaB expression and apoptosis increased from adenoma to poorly differentiated adenocarcinoma. This degenerative transition, recognized as key in carcinogenesis, appear to have been influenced by a diet promoting a pro-inflammatory milieu that can trigger NF-kappaB. Copyright 2009 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

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: yahye.merhi@icm-mhi.org [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)

2012-08-17

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

Functional inhibition of NF-kappa B signal transduction in alpha v alpha beta 3 integrin expressing endothelial cells by using RGD-PEG-modified adenovirus with a mutant I kappa B gene

NARCIS (Netherlands)

Ogawara, K; Kuldo, JM; Oosterhuis, K; Kroesen, BJ; Rots, MG; Trautwein, C; Kimura, T; Haisma, HJ; Molema, G

2006-01-01

In order to selectively block nuclear factor kappa B (NF-kappa B)-dependent signal transduction in angiogenic endothelial cells, we constructed an alpha v beta 3 integrin specific adenovirus encoding dominant negative I kappa B (dnI kappa B) as a therapeutic gene. By virtue of RGD modification of

Kappa statistic for clustered matched-pair data.

Science.gov (United States)

Yang, Zhao; Zhou, Ming

2014-07-10

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

Physico Chemical Characteristic of Kappa Carrageenan Degraded Using Hydrogen Peroxide

Directory of Open Access Journals (Sweden)

Rizky Febriansyah Siregar

2017-02-01

Full Text Available AbstractKappa carrageenan is polysaccharide that widely used in food, pharmaceutical, cosmetic, textile and printing industries as coagulate agent, stabilizer and gelling agent. Hydrogen peroxide (H2O2 is strong oxidator to degrade polysaccharide. Hydrogen peroxide has some advantades such as cheap, easy to get and savety environment. Degradation method using hydrogen peroxide is a technology based on establishment radical hydoxile reactive that attack the glycosidic of polysaccharides as a result reducing in molecular weight of polysaccharide. The aims of this study were to analyze the effect of hydrogen peroxide concentration, temperature and degradation time to molecular weight of refined kappa carrageenan. Structural changes on kappa carrageenan degradation were characterized by viscometer, SEM and FTIR. Hydrogen peroxide concentration, temperature and degradation time were significantly reducing molecular weight and changes in the structural function of refined kappa carrageenan. The lowest molecular weight of refined kappa carrageenan degraded was obtained from the treatment 3% of hydrogen peroxide at temperature 80°C and degradation time for 4 hours.

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

Energy Technology Data Exchange (ETDEWEB)

Woods, Dori C., E-mail: dwoods2@partners.org [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)

2011-06-17

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

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

Directory of Open Access Journals (Sweden)

Петро Васильович Гурський

2015-07-01

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

Circumvention of nuclear factor kappaB-induced chemoresistance by cytoplasmic-targeted anthracyclines.

Science.gov (United States)

Bilyeu, Jennifer D; Panta, Ganesh R; Cavin, Lakita G; Barrett, Christina M; Turner, Eddie J; Sweatman, Trevor W; Israel, Mervyn; Lothstein, Leonard; Arsura, Marcello

2004-04-01

Nuclear factor kappaB (NF-kappaB) has been implicated in inducible chemoresistance against anthracyclines. In an effort to improve the cytotoxicity of anthracyclines while reducing their cardiotoxic effects, we have developed a novel class of extranuclear-localizing 14-O-acylanthracyclines that bind to the phorbol ester/diacylglycerol-binding C1b domain of conventional and novel protein kinase C (PKC) isoforms, thereby promoting an apoptotic response. Because PKCs have been shown to be involved in NF-kappaB activation, in this report, we determined the mechanism of NF-kappaB activation by N-benzyladriamycin-14-valerate (AD 198) and N-benzyladriamycin-14-pivalate (AD 445), two novel 14-O-acylanthracylines. We show that the induction of NF-kappaB activity in response to drug treatment relies on the activation of PKC-delta and NF-kappaB-activating kinase (NAK), independent of ataxia telengectasia mutated and p53 activities. In turn, NAK activates the IKK complex through phosphorylation of the IKK-2 subunit. We find that neither NF-kappaB activation nor ectopic expression of Bcl-X(L) confers protection from AD 198-induced cell killing. Overall, our data indicate that activation of novel PKC isoforms by cytoplasmic-targeted 14-O-acylanthracyclines promotes an apoptotic response independent of DNA damage, which is unimpeded by inducible activation of NF-kappaB.

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.

NF-kappaB signaling: a tale of two pathways in skeletal myogenesis.

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Bakkar, Nadine; Guttridge, Denis C

2010-04-01

NF-kappaB is a ubiquitiously expressed transcription factor that plays vital roles in innate immunity and other processes involving cellular survival, proliferation, and differentiation. Activation of NF-kappaB is controlled by an IkappaB kinase (IKK) complex that can direct either canonical (classical) NF-kappaB signaling by degrading the IkappaB inhibitor and releasing p65/p50 dimers to the nucleus, or causes p100 processing and nuclear translocation of RelB/p52 via a noncanonical (alternative) pathway. Under physiological conditions, NF-kappaB activity is transiently regulated, whereas constitutive activation of this transcription factor typically in the classical pathway is associated with a multitude of disease conditions, including those related to skeletal muscle. How NF-kappaB functions in muscle diseases is currently under intense investigation. Insight into this role of NF-kappaB may be gained by understanding at a more basic level how this transcription factor contributes to skeletal muscle cell differentiation. Recent data from knockout mice support that the classical NF-kappaB pathway functions as an inhibitor of skeletal myogenesis and muscle regeneration acting through multiple mechanisms. In contrast, alternative NF-kappaB signaling does not appear to be required for myofiber conversion, but instead functions in myotube homeostasis by regulating mitochondrial biogenesis. Additional knowledge of these signaling pathways in skeletal myogenesis should aid in the development of specific inhibitors that may be useful in treatments of muscle disorders.

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

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

2018-01-01

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

Improvement of Pulping Uniformity by Measurement of Single Fiber Kappa Number

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Richard R. Gustafson; James B. Callis

2001-11-20

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

Confirmation of linear system theory prediction: Rate of change of Herrnstein's kappa as a function of response-force requirement.

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McDowell, J J; Wood, H M

1985-01-01

Four human subjects worked on all combinations of five variable-interval schedules and five reinforcer magnitudes ( cent/reinforcer) in each of two phases of the experiment. In one phase the force requirement on the operandum was low (1 or 11 N) and in the other it was high (25 or 146 N). Estimates of Herrnstein's kappa were obtained at each reinforcer magnitude. The results were: (1) response rate was more sensitive to changes in reinforcement rate at the high than at the low force requirement, (2) kappa increased from the beginning to the end of the magnitude range for all subjects at both force requirements, (3) the reciprocal of kappa was a linear function of the reciprocal of reinforcer magnitude for seven of the eight data sets, and (4) the rate of change of kappa was greater at the high than at the low force requirement by an order of magnitude or more. The second and third findings confirm predictions made by linear system theory, and replicate the results of an earlier experiment (McDowell & Wood, 1984). The fourth finding confirms a further prediction of the theory and supports the theory's interpretation of conflicting data on the constancy of Herrnstein's kappa.

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

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Genetos, Damian C., E-mail: dgenetos@ucdavis.edu [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)

2011-04-01

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

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

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Tzvia Abramson

Full Text Available 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.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.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.

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

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

2017-04-19

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

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

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Baud, Véronique; Karin, Michael

2009-01-01

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

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

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Hardoko

2006-04-01

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.

Differential regulation of. mu. , delta, kappa opioid receptors by Mn/sup + +/

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Szuecs, M.; Oetting, G.M.; Coscia, C.J.

1986-03-05

Differential effects of Mn/sup + +/ on three opioid receptor subtypes of rat brain membranes were evaluated. Concentration dependency studies performed with 0.05-20 mM Mn/sup + +/ revealed that only the delta receptors are stimulated at any concentration. The binding of 1 nM /sup 3/H-DAGO was not stimulated by low concentrations (< 1mM) of Mn/sup + +/, and was significantly inhibited at higher concentrations (40% at 20 mM). 1 nM /sup 3/H-EKC (+100nM DAGO and 100nM DADLE) binding was inhibited by Mn/sup + +/ in the entire concentration range. While regulation of ..mu.. receptor binding did not change during postnatal development, delta and kappa binding displayed a pronounced developmental time-dependency. Kappa sites were hardly affected by Mn/sup + +/ at day 5, and adult levels of inhibition were reached only after the third week postnatal. In contrast, 1 nM /sup 3/H-DADLE (+10nM DAGO) binding was most sensitive to Mn/sup + +/ on day 5 after birth (100% stimulation with 5-20 mM). The ED/sub 50/ of Mn/sup + +/ stimulation was unchanged during maturation. These immature delta sites displayed a similar extent of Mn/sup + +/ reversal of Gpp(NH)p inhibition as seen in microsomes, which represent a good model of N/sub i/-uncoupled receptors. These data suggest that ..mu.., delta and kappa receptors are differently coupled to N/sub i/. Moreover, a second divalent cation binding site, in addition to that on N/sub i/ might exist for delta receptors.

Parallel sort with a ranged, partitioned key-value store in a high perfomance computing environment

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

2016-01-26

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.

Glycogen synthase kinase-3 inhibition disrupts nuclear factor-kappaB activity in pancreatic cancer, but fails to sensitize to gemcitabine chemotherapy

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Mamaghani Shadi

2009-04-01

Full Text Available Abstract Background Aberrant activation NF-kappaB has been proposed as a mechanism of drug resistance in pancreatic cancer. Recently, inhibition of glycogen synthase kinase-3 has been shown to exert anti-tumor effects on pancreatic cancer cells by suppressing NF-kappaB. Consequently, we investigated whether inhibition of GSK-3 sensitizes pancreatic cancer cells to the chemotherapeutic agent gemcitabine. Methods GSK-3 inhibition was achieved using the pharmacological agent AR-A014418 or siRNA against GSK-3 alpha and beta isoforms. Cytotoxicity was measured using a Sulphorhodamine B assay and clonogenic survival following exposure of six different pancreatic cancer cell lines to a range of doses of either gemcitabine, AR-A014418 or both for 24, 48 and 72 h. We measured protein expression levels by immunoblotting. Basal and TNF-alpha induced activity of NF-kappaB was assessed using a luciferase reporter assay in the presence or absence of GSK-3 inhibition. Results GSK-3 inhibition reduced both basal and TNF-alpha induced NF-kappaB luciferase activity. Knockdown of GSK-3 beta reduced nuclear factor kappa B luciferase activity to a greater extent than GSK-3 alpha, and the greatest effect was seen with dual knockdown of both GSK-3 isoforms. GSK-3 inhibition also resulted in reduction of the NF-kappaB target proteins XIAP, Bcl-XL, and cyclin D1, associated with growth inhibition and decreased clonogenic survival. In all cell lines, treatment with either AR-A014418, or gemcitabine led to growth inhibition in a dose- and time-dependent manner. However, with the exception of PANC-1 where drug synergy occurred with some dose schedules, the inhibitory effect of combined drug treatment was additive, sub-additive, or even antagonistic. Conclusion GSK-3 inhibition has anticancer effects against pancreatic cancer cells with a range of genetic backgrounds associated with disruption of NF-kappaB, but does not significantly sensitize these cells to the standard

Glycogen synthase kinase-3 inhibition disrupts nuclear factor-kappaB activity in pancreatic cancer, but fails to sensitize to gemcitabine chemotherapy

International Nuclear Information System (INIS)

Mamaghani, Shadi; Patel, Satish; Hedley, David W

2009-01-01

Aberrant activation NF-kappaB has been proposed as a mechanism of drug resistance in pancreatic cancer. Recently, inhibition of glycogen synthase kinase-3 has been shown to exert anti-tumor effects on pancreatic cancer cells by suppressing NF-kappaB. Consequently, we investigated whether inhibition of GSK-3 sensitizes pancreatic cancer cells to the chemotherapeutic agent gemcitabine. GSK-3 inhibition was achieved using the pharmacological agent AR-A014418 or siRNA against GSK-3 alpha and beta isoforms. Cytotoxicity was measured using a Sulphorhodamine B assay and clonogenic survival following exposure of six different pancreatic cancer cell lines to a range of doses of either gemcitabine, AR-A014418 or both for 24, 48 and 72 h. We measured protein expression levels by immunoblotting. Basal and TNF-alpha induced activity of NF-kappaB was assessed using a luciferase reporter assay in the presence or absence of GSK-3 inhibition. GSK-3 inhibition reduced both basal and TNF-alpha induced NF-kappaB luciferase activity. Knockdown of GSK-3 beta reduced nuclear factor kappa B luciferase activity to a greater extent than GSK-3 alpha, and the greatest effect was seen with dual knockdown of both GSK-3 isoforms. GSK-3 inhibition also resulted in reduction of the NF-kappaB target proteins XIAP, Bcl-X L , and cyclin D1, associated with growth inhibition and decreased clonogenic survival. In all cell lines, treatment with either AR-A014418, or gemcitabine led to growth inhibition in a dose- and time-dependent manner. However, with the exception of PANC-1 where drug synergy occurred with some dose schedules, the inhibitory effect of combined drug treatment was additive, sub-additive, or even antagonistic. GSK-3 inhibition has anticancer effects against pancreatic cancer cells with a range of genetic backgrounds associated with disruption of NF-kappaB, but does not significantly sensitize these cells to the standard chemotherapy agent gemcitabine. This lack of synergy might be

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

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

1999-01-01

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

Kappa opioid receptors stimulate phosphoinositide turnover in rat brain

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

1990-01-01

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

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

International Nuclear Information System (INIS)

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

1989-01-01

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

Multi-step carboxymethylation of kappa-Carrageenan

International Nuclear Information System (INIS)

Aranilla, Charito Tranquilan; Nagasawa, Naotsugu; Bayquen, Aristea V.

2008-01-01

Many polysaccharide derivatives have been prepared by carboxymethylation reactions in order to increase the range of potential applications of these natural polymers in the chemical, food, pharmaceutical and cosmetic industries. Carboxymethylation of kappa-carrageenan was attempted for the first time to synthesize derivatives with various degree of substitution. A multistep carboxymethylation was performed under heterogeneous reaction conditions, in isopropyl alcohol/water slurry medium, with aqueous sodium hydroxide solution for activation, and monochloroacetic acid for etherification. The derivatives obtained had average degree of substitutions from 1.20 to 1.92 as determined by potentiometric back-titration. Chemical and structural characterization were accomplished by Gel Permeation Chromatography, Elemental analysis, FT-IR Spectroscopy, 1 H N and 13 C NMR Spectroscopy. The relative reactivity of the hydroxyl groups in κ-carrageenan dimer unit proceeded in the order O-C2 G4S > O-C6 G4S >O-C2 AG at a ratio of 1:0.6:O.4. (author)

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

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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: m.a.n.rattray@reading.ac.uk [Reading School of Pharmacy, University of Reading, Reading RG6 6UB (United Kingdom)

2012-02-17

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

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

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

2010-04-01

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

Inhibition of IkappaB kinase-nuclear factor-kappaB signaling pathway by 3,5-bis(2-flurobenzylidene)piperidin-4-one (EF24), a novel monoketone analog of curcumin.

Science.gov (United States)

Kasinski, Andrea L; Du, Yuhong; Thomas, Shala L; Zhao, Jing; Sun, Shi-Yong; Khuri, Fadlo R; Wang, Cun-Yu; Shoji, Mamoru; Sun, Aiming; Snyder, James P; Liotta, Dennis; Fu, Haian

2008-09-01

The nuclear factor-kappaB (NF-kappaB) signaling pathway has been targeted for therapeutic applications in a variety of human diseases, includuing cancer. Many naturally occurring substances, including curcumin, have been investigated for their actions on the NF-kappaB pathway because of their significant therapeutic potential and safety profile. A synthetic monoketone compound termed 3,5-bis(2-flurobenzylidene)piperidin-4-one (EF24) was developed from curcumin and exhibited potent anticancer activity. Here, we report a mechanism by which EF24 potently suppresses the NF-kappaB signaling pathway through direct action on IkappaB kinase (IKK). We demonstrate that 1) EF24 induces death of lung, breast, ovarian, and cervical cancer cells, with a potency about 10 times higher than that of curcumin; 2) EF24 rapidly blocks the nuclear translocation of NF-kappaB, with an IC(50) value of 1.3 microM compared with curcumin, with an IC(50) value of 13 microM; 3) EF24 effectively inhibits tumor necrosis factor (TNF)-alpha-induced IkappaB phosphorylation and degradation, suggesting a role of this compound in targeting IKK; and 4) EF24 indeed directly inhibits the catalytic activity of IKK in an in vitro-reconstituted system. Our study identifies IKK as an effective target for EF24 and provides a molecular explanation for a superior activity of EF24 over curcumin. The effective inhibition of TNF-alpha-induced NF-kappaB signaling by EF24 extends the therapeutic application of EF24 to other NF-kappaB-dependent diseases, including inflammatory diseases such as rheumatoid arthritis.

Generic and updatable XML value indices covering equality and range lookups

NARCIS (Netherlands)

E. Sidirourgos (Eleftherios); P.A. Boncz (Peter)

2008-01-01

htmlabstractWe describe a collection of indices for XML text, element, and attribute node values that (i) consume little storage, (ii) have low maintenance overhead, (iii) permit fast equi-lookup on string values, and (iv) support range-lookup on any XML typed value (e.g., double, dateTime). The

Generic and Updatable XML Value Indices Covering Equality and Range Lookups

NARCIS (Netherlands)

E. Sidirourgos (Eleftherios); P.A. Boncz (Peter)

2009-01-01

textabstractWe describe a collection of indices for XML text, element, and attribute node values that (i) consume little storage, (ii) have low maintenance overhead, (iii) permit fast equilookup on string values, and (iv) support range-lookup on any XML typed value (e.g., double, dateTime). The

Immunoglobulin gene expression and regulation of rearrangement in kappa transgenic mice

International Nuclear Information System (INIS)

Ritchie, K.A.

1986-01-01

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

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

Science.gov (United States)

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

2005-04-01

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

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

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

Energy Technology Data Exchange (ETDEWEB)

Reimers, Kerstin [Klinik fuer Plastische, Hand-und Wiederherstellungschirurgie, Podbielskistrasse 380, D-30659 Hannover (Germany); Buchholz, Katja [Institut fuer Medizinische Mikrobiologie, Otto-von-Guericke-Universitaet Magdeburg, Leipzigerstrasse 44, D-39120 Magdeburg (Germany); Werchau, Hermann [Institut fuer Medizinische Mikrobiologie, Otto-von-Guericke-Universitaet Magdeburg, Leipzigerstrasse 44, D-39120 Magdeburg (Germany)

2005-01-20

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

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.

Science.gov (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

2008-11-01

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

Receptor tyrosine phosphatase R-PTP-kappa mediates homophilic binding

DEFF Research Database (Denmark)

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

1994-01-01

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...... not require PTPase activity or posttranslational proteolytic cleavage of the R-PTP-kappa protein and is calcium independent. The results suggest that R-PTPases may provide a link between cell-cell contact and cellular signaling events involving tyrosine phosphorylation....

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

Science.gov (United States)

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

2001-08-10

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

Normal range values for thromboelastography in healthy adult volunteers

Directory of Open Access Journals (Sweden)

S. Scarpelini

2009-12-01

Full Text Available 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, α, 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, α: 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®.

Macromolecular complexes of lysozyme with kappa carrageenan

NARCIS (Netherlands)

Antonov, Y.A.; Zhuravleva, I.L.; Cardinaels, R.; Moldenaers, P.

2018-01-01

We present a structural study of the complexation and binding of lysozyme (Lys) with kappa carrageenan (kCG) by means of turbidity measurements, phase analysis, dynamic and electrophoretic light scattering, differential scanning microcalorimetry (DSMC), confocal laser scanning (CLSM) microscopy,

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

Science.gov (United States)

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

2014-12-01

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

Gnotobiotic IL-10; NF-kappaB mice develop rapid and severe colitis following Campylobacter jejuni infection.

Directory of Open Access Journals (Sweden)

Elisabeth Lippert

2009-10-01

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.

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

1999-01-01

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......-6596]. Nevertheless, since the transgene's expression is driven by the endogenous RPTP-kappa promoter, distribution of the truncated RPTP-kappa/beta-geo fusion protein should reflect the regional and cellular expression of wild-type RPTP-kappa, and thus may identify sites where RPTP-kappa is important. Towards...... that goal, we have used this mouse model to map the distribution of the truncated RPTP-kappa/beta-geo fusion protein in the adult mouse brain using beta-galactosidase as a marker enzyme. Visualization of the beta-galactosidase activity revealed a non-random pattern of expression, and identified cells...

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

Science.gov (United States)

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

2015-06-01

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

DMPD: New insights into NF-kappaB regulation and function. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 18775672 New insights into NF-kappaB regulation and function. Sun SC, Ley SC. Trend...ction. PubmedID 18775672 Title New insights into NF-kappaB regulation and function....s Immunol. 2008 Oct;29(10):469-78. Epub 2008 Sep 3. (.png) (.svg) (.html) (.csml) Show New insights into NF-kappaB regulation and fun

A Trigger for Opioid Misuse: Chronic Pain and Stress Dysregulate the Mesolimbic Pathway and Kappa Opioid System.

Science.gov (United States)

Massaly, Nicolas; Morón, Jose A; Al-Hasani, Ream

2016-01-01

Pain and stress are protective mechanisms essential in avoiding harmful or threatening stimuli and ensuring survival. Despite these beneficial roles, chronic exposure to either pain or stress can lead to maladaptive hormonal and neuronal modulations that can result in chronic pain and a wide spectrum of stress-related disorders including anxiety and depression. By inducing allostatic changes in the mesolimbic dopaminergic pathway, both chronic pain and stress disorders affect the rewarding values of both natural reinforcers, such as food or social interaction, and drugs of abuse. Despite opioids representing the best therapeutic strategy in pain conditions, they are often misused as a result of these allostatic changes induced by chronic pain and stress. The kappa opioid receptor (KOR) system is critically involved in these neuronal adaptations in part through its control of dopamine release in the nucleus accumbens. Therefore, it is likely that changes in the kappa opioid system following chronic exposure to pain and stress play a key role in increasing the misuse liability observed in pain patients treated with opioids. In this review, we will discuss how chronic pain and stress-induced pathologies can affect mesolimbic dopaminergic transmission, leading to increased abuse liability. We will also assess how the kappa opioid system may underlie these pathological changes.

A trigger for opioid misuse: Chronic pain and stress dysregulate the mesolimbic pathway and kappa opioid system

Directory of Open Access Journals (Sweden)

Nicolas Massaly

2016-11-01

Full Text Available Pain and stress are protective mechanisms essential in avoiding harmful or threatening stimuli and ensuring survival. Despite these beneficial roles, chronic exposure to either pain or stress can lead to maladaptive hormonal and neuronal modulations that can result in chronic pain and a wide spectrum of stress-related disorders including anxiety and depression. By inducing allostatic changes in the mesolimbic dopaminergic pathway, both chronic pain and stress disorders affect the rewarding values of both natural reinforcers, such as food or social interaction, and drugs of abuse. Despite opioids representing the best therapeutic strategy in acute pain conditions, they are often misused as a result of these allostatic changes induced by chronic pain and stress. The kappa opioid receptor system is critically involved in these neuronal adaptations in part through its control of dopamine release in the nucleus accumbens. Therefore, it is likely that changes in the kappa opioid system following chronic exposure to pain and stress play a key role in increasing the misuse liability observed in pain patients treated with opioids. In this review, we will discuss how chronic pain and stress-induced pathologies can affect mesolimbic dopaminergic transmission, leading to increased abuse liability. We will also assess how the kappa opioid system may underlie these pathological changes.

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. Wullaer...vg) (.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

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

1999-01-01

that goal, we have used this mouse model to map the distribution of the truncated RPTP-kappa/beta-geo fusion protein in the adult mouse brain using beta-galactosidase as a marker enzyme. Visualization of the beta-galactosidase activity revealed a non-random pattern of expression, and identified cells......-6596]. Nevertheless, since the transgene's expression is driven by the endogenous RPTP-kappa promoter, distribution of the truncated RPTP-kappa/beta-geo fusion protein should reflect the regional and cellular expression of wild-type RPTP-kappa, and thus may identify sites where RPTP-kappa is important. Towards...

Spectroscopy of the fractional vortex eigenfrequency in a long Josephson 0-{kappa} junction

Energy Technology Data Exchange (ETDEWEB)

Buckenmaier, K.; Gaber, T.; Schittenhelm, I.; Kleiner, R.; Koelle, D.; Goldobin, E. [Physikalisches Inst., Experimentalphysik II, Univ. Tuebingen (Germany); Siegel, M. [Univ. Karlsruhe (Germany). Inst. fuer Mikro- und Nanoelektronische Systeme

2007-07-01

In long Josephson junctions with a {kappa}-phase discontinuity, created by two current injectors, a fractional Josephson vortex (FJV) is spontaneously formed at the interface between the 0- and {kappa}-part. A FJV carries an arbitrary fraction {phi}/{phi}{sub 0}={kappa}/2{pi} of the magnetic flux quantum {phi}{sub 0}{approx}2.07 x 10{sup -15} Wb. In contrast to fluxons, FJVs are pinned at the discontinuity point, but in underdamped systems they are able to oscillate around their equilibrium point with characteristic eigenfrequencies. To experimentally determine the eigenfrequency we stimulated a FJV by irradiating our sample with microwaves. At resonance the junction switches to the resistive state. A measurement of the switching probability thus allows to determine the FJV eigenfrequency as a function of bias current and {kappa}. We compare our results with the prediction of the perturbed sine-Gordon equation. (orig.)

A note on the kappa statistic for clustered dichotomous data.

Science.gov (United States)

Zhou, Ming; Yang, Zhao

2014-06-30

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

Molecular cloning and expression of bovine kappa-casein in Escherichia coli

International Nuclear Information System (INIS)

Kang, Y.C.; Richardson, T.

1988-01-01

A cDNA library was constructed using poly(A) + RNA from bovine mammary gland. This cDNA library of 6000 clones was screened employing colony hybridization using 32 P-labelled oligonucleotide probes and restriction endonuclease mapping. The cDNA from the selected plasmid, pKR76, was sequenced using the dideoxy-chain termination method. The cDNA insert of pKR76 carries the full-length sequence, which codes for mature kappa-casein protein. The amino acid sequence deduced from the cDNA sequence fits the published amino acid sequence with three exceptions; the reported pyroglutamic acid at position 1, tyrosine at position 35, and aspartic acid at position 81 are, respectively, a glutamine, a histidine, and an asparagine in the clone containing pKR76. The MspI-, NlaIV-cleaved fragment (630 base pair) from the kappa-casein cDNA insert has been subcloned into expression vectors pUC18 and pKK233-2, which contain a lac promoter and a trc promoter, respectively. Escherichia coli cells carrying the recombinant expression plasmids were shown to produce kappa-casein protein having the expected mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and being recognized by specific antibodies raised against natural bovine kappa-casein

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

Directory of Open Access Journals (Sweden)

Catherine L Townsend

2016-09-01

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.

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

Science.gov (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

2016-01-01

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

Method for rapidly determining a pulp kappa number using spectrophotometry

Science.gov (United States)

Chai, Xin-Sheng; Zhu, Jun Yong

2002-01-01

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

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

Directory of Open Access Journals (Sweden)

Mark Pogson

2008-06-01

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.

[{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: perrio@cyceron.fr; 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: debruyne@cyceron.fr; 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)

2008-07-15

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.

Persistent activation of NF-kappaB related to IkappaB's degradation profiles during early chemical hepatocarcinogenesis

Directory of Open Access Journals (Sweden)

García-Román Rebeca

2007-04-01

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.

Regulation of development and function of different T cell subtypes by Rel/NF-{kappa}B family members

Energy Technology Data Exchange (ETDEWEB)

Vallabhapurapu, S.

2004-09-01

This study reveals the requirement of distinct members of the Rel/NF-{kappa}B family in both hematopoietic and non-hematopoietic cells for the development of thymic NKT cells. Activation of NF-{kappa}B via the classical I{kappa}B{alpha}-regulated pathway is required within the NKT precursors for their efficient maturation from NK1.1{sup -} precursors to mature NK1.1{sup +} NKT cells. The Rel/NF-{kappa}B family member RelB, on the other hand, is required in thymic stromal cells for the generation of very early NK1.1{sup -} precursors. NF-{kappa}B-inducing kinase (NIK) has also been shown to be required in thymic stromal cells for NKT cell development and this study demonstrates that NIK specifically regulates both constitutive and signal-induced DNA binding of RelB, but not RelA. Moreover, NIK-induced DNA binding of RelB depends on the processing of inhibitory p100 to p52, revealing an alternate pathway of NF-{kappa}B induction. Thus, Rel/NF-{kappa}B complexes activated by the classical I{kappa}B{alpha}-regulated pathway in NKT precursors and an alternate NIK/p100/RelB pathway in thymic stromal cells regulate different stages of NKT cell development. (orig.)

Reproducibility of vibration perception threshold values in children and adolescents with type 1 diabetes mellitus and associated factors.

Science.gov (United States)

Louraki, M; Tsentidis, C; Kallinikou, D; Katsalouli, M; Kanaka-Gantenbein, C; Kafassi, N; Papathanasiou, A; Karavanaki, K

2014-07-01

To define the reproducibility of vibration perception thresholds (VPTs) and the possible associated factors, as an early index of peripheral diabetic neuropathy (PDN) in type 1 diabetes mellitus (T1DM) children and adolescents. A single examiner studied 118 T1DM subjects (aged 13.5±3.4 years) and 79 controls (aged 12.0±3.07 years). Glycaemic control was assessed with HbA1c levels. VPT was measured twice on upper and lower limbs, using a Biothesiometer. Concordance between the two VPT measurements was evaluated using the Cohen's Weighted Kappa statistic (Kappa=0.41-0.60→moderate concordance, Kappa=0.61-0.80→substantial concordance). T1DM children had significantly higher VPTs than controls at all sites (p=0.001), but with lower Kappa values (0.64-0.70). VPT values increased in parallel with HbA1c (a.9.5%) and T1DM duration (a.1-10, c.>10 years). However, Kappa values were lower in the groups with the poorest control (HbA1c>9.5%) (Kappa=0.54-0.76) or the longest T1DM duration (>10 years) (Kappa=0.49-0.71). Although VPTs increased with stature and male gender, no effect on VPT reproducibility was observed. However, obesity was associated with lower VPT values and poorer concordance. These findings suggest that the reproducibility of VPTs is lower in the high-risk patients for early subclinical PDN development, who need a regular follow-up. Copyright © 2013 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

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

Science.gov (United States)

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

2006-07-01

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

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.

R-matrix-valued Lax pairs and long-range spin chains

Science.gov (United States)

Sechin, I.; Zotov, A.

2018-06-01

In this paper we discuss R-matrix-valued Lax pairs for slN Calogero-Moser model and their relation to integrable quantum long-range spin chains of the Haldane-Shastry-Inozemtsev type. First, we construct the R-matrix-valued Lax pairs for the third flow of the classical Calogero-Moser model. Then we notice that the scalar parts (in the auxiliary space) of the M-matrices corresponding to the second and third flows have form of special spin exchange operators. The freezing trick restricts them to quantum Hamiltonians of long-range spin chains. We show that for a special choice of the R-matrix these Hamiltonians reproduce those for the Inozemtsev chain. In the general case related to the Baxter's elliptic R-matrix we obtain a natural anisotropic extension of the Inozemtsev chain. Commutativity of the Hamiltonians is verified numerically. Trigonometric limits lead to the Haldane-Shastry chains and their anisotropic generalizations.

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

Science.gov (United States)

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

2015-08-01

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

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

Science.gov (United States)

Hu, Bingjie; Du, Lei; Matsukawa, Shingo

2016-10-05

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

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

Energy Technology Data Exchange (ETDEWEB)

Togano, Tomiteru; Sasaki, Masataka; Watanabe, Mariko; Nakashima, Makoto [Department of Hematology, School of Medicine, Kitasato University, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555 (Japan); Tsuruo, Takashi [Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-10-6 Ariake, Koto-ku, Tokyo 135-8550 (Japan); Umezawa, Kazuo [Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-0061 (Japan); Higashihara, Masaaki [Department of Hematology, School of Medicine, Kitasato University, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555 (Japan); Watanabe, Toshiki [Laboratory of Tumor Cell Biology, Department of Medical Genome Sciences, Graduate School of Frontier Sciences, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Horie, Ryouichi, E-mail: rhorie@med.kitasato-u.ac.jp [Department of Hematology, School of Medicine, Kitasato University, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555 (Japan)

2009-12-04

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

on skin keratinocytes by nuclear factor-kappa B

African Journals Online (AJOL)

DR. NJ TONUKARI

2012-06-21

Jun 21, 2012 ... Effects of advanced glycation end-products (AGEs) on ... AGE levels, nuclear factor-kappa B (NF-κB) localization and cell viability were measured in vivo. ..... and related alteration in NF-κB activity, we treated normal cells by ...

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

Science.gov (United States)

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

2016-05-01

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

Commutators of Littlewood-Paley gκ∗$g_{\\kappa}^{*} $-functions on non-homogeneous metric measure spaces

Directory of Open Access Journals (Sweden)

Lu Guanghui

2017-11-01

Full Text Available The main purpose of this paper is to prove that the boundedness of the commutator Mκ,b∗$\\mathcal{M}_{\\kappa,b}^{*} $ generated by the Littlewood-Paley operator Mκ∗$\\mathcal{M}_{\\kappa}^{*} $ and RBMO (μ function on non-homogeneous metric measure spaces satisfying the upper doubling and the geometrically doubling conditions. Under the assumption that the kernel of Mκ∗$\\mathcal{M}_{\\kappa}^{*} $ satisfies a certain Hörmander-type condition, the authors prove that Mκ,b∗$\\mathcal{M}_{\\kappa,b}^{*} $ is bounded on Lebesgue spaces Lp(μ for 1 < p < ∞, bounded from the space L log L(μ to the weak Lebesgue space L1,∞(μ, and is bounded from the atomic Hardy spaces H1(μ to the weak Lebesgue spaces L1,∞(μ.

Measurement of Shoulder Range of Motion in Patients with Adhesive Capsulitis Using a Kinect.

Directory of Open Access Journals (Sweden)

Seung Hak Lee

Full Text Available 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.

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: zhongxia1977@126.com [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: wenhuashenghuo1@163.com [Department of Emergency, Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China)

2012-08-24

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

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

Energy Technology Data Exchange (ETDEWEB)

Galvao, R. A.; Ziebell, L. F. [Instituto de Fisica, Universidade Federal do Rio Grande do Sul, Caixa Postal 15051, CEP: 91501-970, Porto Alegre, Rio Grande do Sul (Brazil); Gaelzer, R. [Instituto de Fisica e Matematica, Universidade Federal de Pelotas, Caixa Postal 354-Campus UFPel, CEP: 96010-900 Pelotas, Rio Grande do Sul (Brazil); Juli, M. C. de [Centro de Radio-Astronomia e Astrofisica Mackenzie-CRAAM, Universidade Presbiteriana Mackenzie, Rua da Consolacao 896, CEP: 01302-907 Sao Paulo, Sao Paulo (Brazil)

2012-12-15

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

Behavioral meaningful opioidergic stimulation activates kappa receptor gene expression

Directory of Open Access Journals (Sweden)

E. Teodorov

2012-10-01

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

Application of the kappa statistic in MRI diagnosis of lumbar disk herniation

International Nuclear Information System (INIS)

Li Dasheng; Zhang Fang; Gao Shuming; Gu Jinxiang; Li Lu; Qu Hui

2008-01-01

Objective: To assess the concordance of MRI diagnosis for patients suspected of lumbar disk herniation by using Kappa statistic. Methods: One hundred patients (48 males and 52 females) with lumbosacral radiculm pain, aged from 17 to 86 (average 61). All patients underwent fast spin-echo T 1 and T 2 weighted imaging on a 3.0 T MR scanner and spine surface coil. Two radiologists (doctor A and doctor B) evaluated the lumbar disks from L3-4, L4-5, and L5-S1 in 50 out of the 100 patients independently. The presence of a bulging disk or a herniation was reported. Images were interpreted twice: once before and once after disclosure of clinical information. And disks of 52 patients out of the 100 samples were interpreted by the two radiologists independently without clinical information as well. The Kappa statistics was employed to assess the concordance of each radiologist's diagnoses as well as the observer variation of the two radiologists. Results: Diagnoses before and after disclosure to clinical information were concordant in 114 disks for doctor A and in 109 for doctor B, respectively. Diagnoses before and after disclosure to clinical information were not concordant in 36 disks for doctor A and in 41 disks for doctor B, respectively. The Kappa values were 0.60±0.06 and 0.57±0.06 for doctor A and doctor B, respectively. The concordance was moderate. After disclosure to clinical information, the numbers of reported bulging disks increased significantly, by 10 and 31 for doctor A and doctor B, respectively. Without clinical information, the diagnoses of the two radiologists were concordant in 77 disks, while not concordant in 79 disks. The interobserver agreement was poor (Kappa=0.24±0.06). The difference on diagenoses made between with and without clinical information mainly happened on the differential diagnosis of normal disks and bulging disks. The different diagnoses made between with and without clinical information were on 20 disks and on 30 disks for doctor

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

OpenAIRE

Begun, D J; Whitley, P

2000-01-01

NF-kappaB and IkappaB proteins have central roles in regulation of inflammation and innate immunity in mammals. Homologues of these proteins also play an important role in regulation of the Drosophila immune response. Here we present a molecular population genetic analysis of Relish, a Drosophila NF-kappaB/IkappaB protein, in Drosophila simulans and D. melanogaster. We find strong evidence for adaptive protein evolution in D. simulans, but not in D. melanogaster. The adaptive evolution appear...

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

Science.gov (United States)

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

2010-06-01

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

NIRS Characterization of Paper Pulps to Predict Kappa Number

Directory of Open Access Journals (Sweden)

Ana Moral

2015-01-01

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.

Hydrogen inhalation reduced epithelial apoptosis in ventilator-induced lung injury via a mechanism involving nuclear factor-kappa B activation

Energy Technology Data Exchange (ETDEWEB)

Huang, Chien-Sheng [Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA (United States); Division of Thoracic Surgery, Department of Surgery, Taipei-Veterans General Hospital and National Yang-Ming University School of Medicine, Taipei, Taiwan (China); Kawamura, Tomohiro; Peng, Ximei [Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA (United States); Tochigi, Naobumi [Department of Pathology, University of Pittsburgh Medical Center, PA (United States); Shigemura, Norihisa [Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA (United States); Billiar, Timothy R. [Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA (United States); Nakao, Atsunori, E-mail: anakao@imap.pitt.edu [Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA (United States); Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA (United States); Toyoda, Yoshiya [Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA (United States)

2011-05-06

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

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

Energy Technology Data Exchange (ETDEWEB)

Kabuta, Tomohiro [Departments of Animal Sciences and Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo 113-8657 (Japan); Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502 (Japan); Hakuno, Fumihiko; Cho, Yoshitake; Yamanaka, Daisuke; Chida, Kazuhiro [Departments of Animal Sciences and Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo 113-8657 (Japan); Asano, Tomoichiro [Graduate School of Biomedical Science, Hiroshima University, Hiroshima 734-8551 (Japan); Wada, Keiji [Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502 (Japan); Takahashi, Shin-Ichiro, E-mail: atkshin@mail.ecc.u-tokyo.ac.jp [Departments of Animal Sciences and Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo 113-8657 (Japan)

2010-04-09

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

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

Lifescience Database Archive (English)

Full Text Available 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. Pub...medID 18029230 Title Signaling to NF-kappaB by Toll-like receptors. Authors Kawai T

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

International Nuclear Information System (INIS)

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

1986-01-01

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

RANGE AND DISTRIBUTION OF TECHNETIUM KD VALUES IN THE SRS SUBSURFACE ENVIRONMENT

International Nuclear Information System (INIS)

Kaplan, D.

2008-01-01

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 d values) are input parameters used in PA calculations to provide a measure of radionuclide sorption to sediment; the greater the K d value, the greater the sorption and the slower the estimated movement of the radionuclide through sediment. Understanding and quantifying K 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 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 4 - ), 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 4 - sorbs to sediments, (2) the range of Tc K d values, (3) the distribution (normal or log-normal) of Tc K d values, and (4) how strongly Tc sorbs to SRS sediments through desorption experiments. Objective 3, to identify the Tc K 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 d values and then perform statistical analysis to describe the measured Tc K d values. The mean K 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 mL/g. The E-Area subsurface is subdivided into three hydrostratigraphic

Mapping the transcription termination region of the mouse immunoglobulin kappa gene

International Nuclear Information System (INIS)

Xu, M.; Garrard, W.T.

1986-01-01

To define the transcription termination region of the mouse immunoglobulin kappa gene, they have subcloned single copy DNA sequences corresponding to both the template and the non-template strands of this locus. In vitro nuclear transcription with isolated MPC-11 nuclei was performed and the resulting 32 P-labeled RNA was hybridized to slot-blotted, single-stranded M13 probes covering regions within and flanking the kappa gene. The hybridization pattern for the template-strand reveals that transcription terminates within the region between 1.1 to 2.3 kb downstream from the poly(A) site. Ten different short sequences (8-13 bp) reside within 460 bp of this region that exhibit homology with sequences found in the termination regions of mouse β-globin and chicken ovalbumin genes. Transcription of the non-template strand occurs on either side of this termination region. They note that no transcription is detectable on the non-template strand downstream of the enhancer, indicating that if RNA polymerase II enters at this site, it does not initiate transcription during transit to the promoter region. They conclude that transcription of the kappa gene passes the poly(A) addition site and terminates within 2.3 Kb downstream

The Value Range of Contact Stiffness Factor between Pile and Soil Based on Penalty Function

Science.gov (United States)

Chen, Sandy H. L.; Wu, Xinliu

2018-03-01

The value range of contact stiffness factor based on penalty function is studied when we use finite element software ANSYS to analyze contact problems, take single pile and soil of a certain project for example, the normal contact between pile and soil is analyzed with 2D simplified model in horizontal load. The study shows that when adopting linear elastic model to simulate soil, the maximum contact pressure and penetration approach steady value as the contact stiffness factor increases. The reasonable value range of contact stiffness factor reduces as the underlying element thickness decreases, but the rule reverses when refers to the soil stiffness. If choose DP model to simulate soil, the stiffness factor should be magnified 100 times compares to the elastic model regardless of the soil bears small force and still in elastic deformation stage or into the plastic deformation stage. When the soil bears big force and into plastic deformation stage, the value range of stiffness factor relates to the plastic strain range of the soil, and reduces as the horizontal load increases.

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 receptorsignaling. Carmody...uclear factor-kappaB: activation and regulation during toll-like receptorsignaling. Authors Carmody

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: yuanxiaoqd@163.com [Department of Orthodontics, The Affiliated Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong Province 266075 (China); Shen, Gang, E-mail: ganshen2007@163.com [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)

2010-01-01

p38 MAPK and nuclear factor-B (NF-B) signaling pathways play an indispensable role in the control of skeletal myogenesis. The specific contribution of these signaling pathways to the response of myoblast to the mechanical stimulation and the molecular mechanisms underlying this response remain unresolved. Using an established in vitro model, we now show that p38 MAP kinase activity regulates the transcriptional activation of NF-{kappa}B in response to mechanical stimulation of myoblasts. Furthermore, SB203580 blocked stretch-induced NF-{kappa}B activation during myogenesis, not through down-regulation of degradation of I{kappa}B-{alpha}, and consequent translocation of the p65 subunit of NF-{kappa}B to the nucleus. It is 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.

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.

2005-01-01

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. ...... are irreversibly associated, CMP in kappa-CN may associate reversibly in a pH-dependent manner. We suggest that interactions between para-kappa-CN parts of the kappa-CN molecules may be a requisite for the pH-dependent dissociation/association....

Diagnostic Value of 64-Slice Dual-Source CT Coronary Angiography in Patients with Atrial Fibrillation: Comparison with Invasive Coronary Angiography

International Nuclear Information System (INIS)

Zhang, Jian Jun; Liu, Tie; Feng, Yue; Wu, Wei Feng; Mou, Cai Yun; Zhai, Li Hao

2011-01-01

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.

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)

2011-08-15

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.

Corneal NF-kappaB activity is necessary for the retention of transparency in the cornea of UV-B-exposed transgenic reporter mice.

Science.gov (United States)

Alexander, George; Carlsen, Harald; Blomhoff, Rune

2006-04-01

To determine the dynamics of Nuclear Factor-kappaB (NF-kappaB) in murine corneal pathology and the role of NF-kappaB in maintaining corneal clarity after ultraviolet B radiation insult, transgenic mice containing NF-kappaB-luciferase reporter were exposed to LPS (bacterial lipopolysaccharide), TNF-alpha (Tumor Necrosis Factor-alpha) or 4 kJ m(-2) UV-B radiation. NF-kappaB decoy oligonucleotides were also administered in some of the UV-B experiments. Following various exposure times, the mice were sacrificed and whole eyes or corneal tissues were obtained. Whole eyes were examined for scattering using a point-source optical imaging technique. Tissue homogenates were examined for luciferase activity using a luminometer. TNF-alpha and LPS-injected NF-kappaB-luciferase transgenic mice demonstrated 3-10-fold increases in cornea NF-kappaB with peak activities at 4 and 6 hr post-injection, respectively. Mice exposed to 4 kJ m(-2) UV-B exhibited a 3-fold increase in NF-kappaB activity 4 hr post-exposure. The administration of NF-kappaB-decoy oligonucleotides to mice had the effect of reducing UV-B-induced NF-kappaB activity in the cornea and significantly increasing the amount of light scattering in UV-B exposed corneas 7 days post-UV-B exposure when compared to sham injected mice. These results indicate that NF-kappaB is activated in cornea in pathologies that involves increased plasma levels of LPS and TNF-alpha, as well as direct UV-B exposure, and suggest that NF-kappaB activation play an essential part in the corneal healing process.

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

2010-01-01

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) recepto...

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

Science.gov (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

2014-11-07

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

Bmi-1 promotes the aggressiveness of glioma via activating the NF-kappaB/MMP-9 signaling pathway

International Nuclear Information System (INIS)

Jiang, Lili; Wu, Jueheng; Yang, Yi; Liu, Liping; Song, Libing; Li, Jun; Li, Mengfeng

2012-01-01

The prognosis of human glioma is poor, and the highly invasive nature of the disease represents a major impediment to current therapeutic modalities. The oncoprotein B-cell-specific Moloney murine leukemia virus integration site 1 protein (Bmi-1) has been linked to the development and progression of glioma; however, the biological role of Bmi-1 in the invasion of glioma remains unclear. A172 and LN229 glioma cells were engineered to overexpress Bmi-1 via stable transfection or to be silenced for Bmi-1 expression using RNA interfering method. Migration and invasiveness of the engineered cells were assessed using wound healing assay, Transwell migration assay, Transwell matrix penetration assay and 3-D spheroid invasion assay. MMP-9 expression and activity were measured using real-time PCR, ELISA and the gelatin zymography methods. Expression of NF-kappaB target genes was quantified using real-time PCR. NF-kappaB transcriptional activity was assessed using an NF-kappaB luciferase reporter system. Expression of Bmi-1 and MMP-9 in clinical specimens was analyzed using immunohistochemical assay. Ectopic overexpression of Bmi-1 dramatically increased, whereas knockdown of endogenous Bmi-1 reduced, the invasiveness and migration of glioma cells. NF-kappaB transcriptional activity and MMP-9 expression and activity were significantly increased in Bmi-1-overexpressing but reduced in Bmi-1-silenced cells. The reporter luciferase activity driven by MMP-9 promoter in Bmi-1-overexpressing cells was dependent on the presence of a functional NF-kappaB binding site, and blockade of NF-kappaB signaling inhibited the upregulation of MMP-9 in Bmi-1 overexpressing cells. Furthermore, expression of Bmi-1 correlated with NF-kappaB nuclear translocation as well as MMP-9 expression in clinical glioma samples. Bmi-1 may play an important role in the development of aggressive phenotype of glioma via activating the NF-kappaB/MMP-9 pathway and therefore might represent a novel therapeutic

Bmi-1 promotes the aggressiveness of glioma via activating the NF-kappaB/MMP-9 signaling pathway

Directory of Open Access Journals (Sweden)

Jiang Lili

2012-09-01

Full Text Available Abstract Background The prognosis of human glioma is poor, and the highly invasive nature of the disease represents a major impediment to current therapeutic modalities. The oncoprotein B-cell-specific Moloney murine leukemia virus integration site 1 protein (Bmi-1 has been linked to the development and progression of glioma; however, the biological role of Bmi-1 in the invasion of glioma remains unclear. Methods A172 and LN229 glioma cells were engineered to overexpress Bmi-1 via stable transfection or to be silenced for Bmi-1 expression using RNA interfering method. Migration and invasiveness of the engineered cells were assessed using wound healing assay, Transwell migration assay, Transwell matrix penetration assay and 3-D spheroid invasion assay. MMP-9 expression and activity were measured using real-time PCR, ELISA and the gelatin zymography methods. Expression of NF-kappaB target genes was quantified using real-time PCR. NF-kappaB transcriptional activity was assessed using an NF-kappaB luciferase reporter system. Expression of Bmi-1 and MMP-9 in clinical specimens was analyzed using immunohistochemical assay. Results Ectopic overexpression of Bmi-1 dramatically increased, whereas knockdown of endogenous Bmi-1 reduced, the invasiveness and migration of glioma cells. NF-kappaB transcriptional activity and MMP-9 expression and activity were significantly increased in Bmi-1-overexpressing but reduced in Bmi-1-silenced cells. The reporter luciferase activity driven by MMP-9 promoter in Bmi-1-overexpressing cells was dependent on the presence of a functional NF-kappaB binding site, and blockade of NF-kappaB signaling inhibited the upregulation of MMP-9 in Bmi-1 overexpressing cells. Furthermore, expression of Bmi-1 correlated with NF-kappaB nuclear translocation as well as MMP-9 expression in clinical glioma samples. Conclusions Bmi-1 may play an important role in the development of aggressive phenotype of glioma via activating the NF-kappa

Novel selective kappa-opioid ligands.

Science.gov (United States)

Peeters, O M; Jamroz, D; Blaton, N M; De Ranter, C J

1999-03-15

The single-crystal X-ray structures of (-)-dimethyl[(2S)-1-(5,6,7,8- tetrahydro-5-oxonaphthalene-2-acetyl)piperidin-2-ylmethyl ]ammonium chloride, C20H29N2O2+.Cl-(BRL-53001A), and (-)-ethylmethyl[(2S)-1-(5,6,7,8-tetrahydro-5-oxonaphthalene- 2- acetyl)piperidin-2-ylmethyl]-ammonium chloride dihydrate, C21H31N2O2+.Cl-.2H2O (BRL-53188A), have been determined. The two molecules have different conformations in the 1-tetralon-6-ylacetyl residue but the same conformation in the 1-acetyl-2-(dialkylaminomethyl)piperidine moiety. The conformations found are in agreement with the required chemical features for kappa affinity and antinociceptive potency.

Application of iota and kappa carrageenans to traditional several food using modified cassava flour

Science.gov (United States)

Al-Baarri, A. N.; Legowo, A. M.; Rizqiati, H.; Widayat; Septianingrum, A.; Sabrina, H. N.; Arganis, L. M.; Saraswati, R. O.; Mochtar, Rr C. P. R.

2018-01-01

Carrageenan has been known well as hydrocolloids that forming viscous dispersions and gels when dispersed in water. The carrageenan has not been widely applied to traditional foods. Therefore, the aim of this research was to determine the effect of kappa and iota carrageenans in traditional food models using modified cassava flour, sugar, and coconut milk. The textural properties, i.e. hardness, cohesiveness, springiness and adhesiveness have been measured using texture analyzer. The study indicated that traditional food models added kappa carrageenan at 2% generated remarkably higher in the hardness, cohesiveness, and springiness than those added iota carrageenan. On the other hand, the reserve result were found in the adhesiveness parameter. As conclusion, kappa carrageenan scan be potentially used for producing traditional foods based on the hard-texture-oriented foods whereas iota carrageenan can be used for the traditional foods with better adhesiveness.

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: andrea.richter@umontreal.ca [Genetique Medicale, Centre de Recherche CHU Sainte-Justine, Departement de Pediatrie, Universite de Montreal, Montreal, QC (Canada)

2009-11-01

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.

Species contributions to single biodiversity values under-estimate whole community contribution to a wider range of values to society.

Science.gov (United States)

Hiron, Matthew; Pärt, Tomas; Siriwardena, Gavin M; Whittingham, Mark J

2018-05-03

A major task for decision makers is deciding how to consider monetary, cultural and conservation values of biodiversity explicitly when planning sustainable land use. Thus, there is a great need to understand just what "valuing" biodiversity or species really means, e.g. regarding how many and which species are important in providing ecosystem services or other values. Constructing ecosystem-level indices, however, requires weighting the relative contribution of species to the different values. Using farmland birds, we illustrate how species contribute to different biodiversity values, namely utilitarian (pest seed predation potential), cultural (species occurrence in poetry), conservational (declines and rarity) and inherent (all species equal) value. Major contributions to each value are often made by a subset of the community and different species are important for different values, leading to no correlations or, in some cases, negative correlations between species' relative contributions to different values. Our results and methods using relative contributions of species to biodiversity values can aid decisions when weighing different values in policies and strategies for natural resource management. We conclude that acknowledging the importance of the range of biodiversity values that are apparent from different perspectives is critical if the full value of biodiversity to society is to be realised.

A quantum inspired model of radar range and range-rate measurements with applications to weak value measurements

Science.gov (United States)

Escalante, George

2017-05-01

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.

New treatment of periodontal diseases by using NF-kappaB decoy oligodeoxynucleotides via prevention of bone resorption and promotion of wound healing.

Science.gov (United States)

Shimizu, Hideo; Nakagami, Hironori; Morita, Shosuke; Tsukamoto, Ikuyo; Osako, Mariana Kiomy; Nakagami, Futoshi; Shimosato, Takashi; Minobe, Noriko; Morishita, Ryuichi

2009-09-01

Nuclear factor-kappa B (NF-kappaB) is involved in osteoclast differentiation and activation. Thus, the blockade of the NF-kappaB pathway might be a novel therapeutic strategy for treating bone metabolic diseases. Periodontitis is subgingival inflammation caused by bacterial infection; this disease also is thought to be a chronic focal point responsible for systemic diseases. In this study, NF-kappaB decoy oligodeoxynucleotides (ODNs) were topically applied for experimental periodontitis in a debris-accumulation model and wound healing in a bone-defect model of beagle dogs to investigate the effect of decoy ODN on bone metabolism. Application of NF-kappaB decoy ODN significantly reduced interleukin-6 activity in crevicular fluid and improved alveolar bone loss in the analysis of dental radiographs and DEXA. Direct measurement of exposed root that lost alveolar bone support revealed that NF-kappaB decoy treatment dramatically protected bone from loss. In a bone-defect model, NF-kappaB decoy ODN promoted the healing process as compared with control scrambled decoy in micro-CT analysis. Overall, inhibition of NF-kappaB by decoy strategy prevented the progression of bone loss in periodontitis and promoted the wound healing in bone defects through the inhibition of osteoclastic bone resorption. Targeting of NF-kappaB might be a potential therapy in various bone metabolic diseases.

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: ygkwon@yonsei.ac.kr [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of)

2012-05-04

Highlights: Black-Right-Pointing-Pointer IL-33 as nuclear factor regulated expression of ICAM-1 and VCAM-1. Black-Right-Pointing-Pointer Nuclear IL-33 increased the transcription of NF-{kappa}B p65 by binding to the p65 promoter. Black-Right-Pointing-Pointer Nuclear IL-33 controls NF-{kappa}B-dependent inflammatory responses. -- Abstract: Interleukin (IL)-33, an IL-1 family member, acts as an extracellular cytokine by binding its cognate receptor, ST2. IL-33 is also a chromatin-binding transcriptional regulator highly expressed in the nuclei of endothelial cells. However, the function of IL-33 as a nuclear factor is poorly defined. Here, we show that IL-33 is a novel transcriptional regulator of the p65 subunit of the NF-{kappa}B complex and 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.

Homophilic interactions mediated by receptor tyrosine phosphatases mu and kappa. A critical role for the novel extracellular MAM domain

DEFF Research Database (Denmark)

Zondag, G C; Koningstein, G M; Jiang, Y P

1995-01-01

and is found in diverse transmembrane proteins, is not known. We previously reported that both RPTP mu and RPTP kappa can mediate homophilic cell interactions when expressed in insect cells. Here we show that despite their striking structural similarity, RPTP mu and RPTP kappa fail to interact...... in a heterophilic manner. To examine the role of the MAM domain in homophilic binding, we expressed a mutant RPTP mu lacking the MAM domain in insect Sf9 cells. Truncated RPTP mu is properly expressed at the cell surface but fails to promote cell-cell adhesion. Homophilic cell adhesion is fully restored...... in a chimeric RPTP mu molecule containing the MAM domain of RPTP kappa. However, this chimeric RPTP mu does not interact with either RPTP mu or RPTP kappa. These results indicate that the MAM domain of RPTP mu and RPTP kappa is essential for homophilic cell-cell interaction and helps determine the specificity...

New approach for the identification of implausible values and outliers in longitudinal childhood anthropometric data.

Science.gov (United States)

Shi, Joy; Korsiak, Jill; Roth, Daniel E

2018-03-01

We aimed to demonstrate the use of jackknife residuals to take advantage of the longitudinal nature of available growth data in assessing potential biologically implausible values and outliers. Artificial errors were induced in 5% of length, weight, and head circumference measurements, measured on 1211 participants from the Maternal Vitamin D for Infant Growth (MDIG) trial from birth to 24 months of age. Each child's sex- and age-standardized z-score or raw measurements were regressed as a function of age in child-specific models. Each error responsible for a biologically implausible decrease between a consecutive pair of measurements was identified based on the higher of the two absolute values of jackknife residuals in each pair. In further analyses, outliers were identified as those values beyond fixed cutoffs of the jackknife residuals (e.g., greater than +5 or less than -5 in primary analyses). Kappa, sensitivity, and specificity were calculated over 1000 simulations to assess the ability of the jackknife residual method to detect induced errors and to compare these methods with the use of conditional growth percentiles and conventional cross-sectional methods. Among the induced errors that resulted in a biologically implausible decrease in measurement between two consecutive values, the jackknife residual method identified the correct value in 84.3%-91.5% of these instances when applied to the sex- and age-standardized z-scores, with kappa values ranging from 0.685 to 0.795. Sensitivity and specificity of the jackknife method were higher than those of the conditional growth percentile method, but specificity was lower than for conventional cross-sectional methods. Using jackknife residuals provides a simple method to identify biologically implausible values and outliers in longitudinal child growth data sets in which each child contributes at least 4 serial measurements. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

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: kerstin.hilt@charite.de [Allergie-Centrum-Charite, CCM, Klinik fuer Dermatologie und Allergologie, Charite - Universitaetsmedizin Berlin, Chariteplatz 1, 10117 Berlin (Germany); Heine, Guido, E-mail: guido.heine@charite.de [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: bjoern.hartmann@charite.de [Allergie-Centrum-Charite, CCM, Klinik fuer Dermatologie und Allergologie, Charite - Universitaetsmedizin Berlin, Chariteplatz 1, 10117 Berlin (Germany); Baumgrass, Ria, E-mail: baumgrass@drfz.de [Deutsches Rheuma-Forschungszentrum Berlin, Chariteplatz 1, 10117 Berlin (Germany); Radbruch, Andreas, E-mail: radbruch@drfz.de [Deutsches Rheuma-Forschungszentrum Berlin, Chariteplatz 1, 10117 Berlin (Germany); Worm, Margitta, E-mail: margitta.worm@charite.de [Allergie-Centrum-Charite, CCM, Klinik fuer Dermatologie und Allergologie, Charite - Universitaetsmedizin Berlin, Chariteplatz 1, 10117 Berlin (Germany)

2011-04-22

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.

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

Science.gov (United States)

Imran, Ali KHAN; G, MURTAZA

2018-03-01

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

The impact of kappa number composition on eucalyptus kraft pulp bleachability

Directory of Open Access Journals (Sweden)

M. M. Costa

2007-03-01

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.

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)

2010-06-15

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.)

Binding of kappa- and sigma-opiates in rat brain

International Nuclear Information System (INIS)

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

1982-01-01

Detailed displacements of [ 3 H]dihydromorphine by ketocyclazocine and SKF 10,047, [ 3 H]ethylketocyclazocine by SKF 10,047, and [ 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 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 [ 3 H]dihydromorphine (KD . 3 nM), [ 3 H]ethylketocyclazocine (KD . 4 nM), [ 3 H]SKF 10,047 (KD . 6 nM), and D-Ala2-D-Leu5-[ 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

Ultraviolet inactivation and photoreactivation of the cholera phage 'Kappa'

International Nuclear Information System (INIS)

Samad, S.A.; Bhattacharyya, S.C.; Chatterjee, S.N.

1987-01-01

The lysogenic cholera phage, 'Kappa' is some ten to twenty folds more resistant to UV (254 nm) than are most of the T. phages of E. coli, or the cholera phage PL 163/10, or the host V. cholerae strain H218 Sm r , the 37% (D 37 ) and 10% (D 10 ) survival doses being 255.8 J/m 2 and 633.6 J/m 2 respectively. The UV-irradiated 'Kappa' phages could be photoreactivated in the host V. cholerae strain H218 Sm r to a maximum extent of 40%. The removal of the number of lethal hits per phage by the survival-enhancement treatment (photoreactivation) with time followed an exponential relation, the constant probability of removal of lethal hit per unit time being 2.8x10 -2 min -1 . The UV-irradiated phages could also be Weigle reactivated in the host strain of H218 Sm r by a small degree, the maximum reactivation factor (ratio of survivals in UV-irradiated and non-irradiated hosts) being 1.50. (orig.)

Tungsten phosphanylarylthiolato complexes [W{PhP(2-SC6H4)2-kappa3S,S',P} 2] and [W{P(2-SC6H4)3-kappa4S,S',S",P}2]: synthesis, structures and redox chemistry.

Science.gov (United States)

Hildebrand, Alexandra; Lönnecke, Peter; Silaghi-Dumitrescu, Luminita; Hey-Hawkins, Evamarie

2008-09-14

PhP(2-SHC6H4)2 (PS2H2) reacts with WCl6 with reduction of tungsten to give the air-sensitive tungsten(IV) complex [W{PhP(2-SC6H4)2-kappa(3)S,S',P}2] (1). 1 is oxidised in air to [WO{PhPO(2-SC6H4)2-kappa(3)S,S',O}{PhP(2-SC6H4)2-kappa(3)S,S',P}] (2). The attempted synthesis of 2 by reaction of 1 with iodosobenzene as oxidising agent was unsuccessful. [W{P(2-SC6H4)3-kappa(4)S,S',S",P}2] (3) was formed in the reaction of P(2-SHC6H4)3 (PS3H3) with WCl6. The W(VI) complex 3 contains two PS3(3-) ligands, each coordinated in a tetradentate fashion resulting in a tungsten coordination number of eight. The reaction of 3 with AgBF4 yields the dinuclear tungsten complex [W2{P(2-SC6H4)3-kappa(4)S,S',S",P}3]BF4 (4). Complexes 1-4 were characterised by spectral methods and X-ray structure determination.

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

Indian Academy of Sciences (India)

Abstract. Arbitrary amplitude dust-acoustic (DA) solitary waves in an unmagnetized and col- lisionless quantum dusty plasma comprising cold dust particles, kappa (κ)-distributed ions and degenerate electrons are investigated. The influence of suprathermality and quantum effects on the linear dispersion relation of DA ...

An improved Fuzzy Kappa statistic that accounts for spatial autocorrelation

NARCIS (Netherlands)

Hagen - Zanker, A.H.

2009-01-01

The Fuzzy Kappa statistic expresses the agreement between two categorical raster maps. The statistic goes beyond cell-by-cell comparison and gives partial credit to cells based on the categories found in the neighborhood. When matching categories are found at shorter distances the agreement is

Proteasome and NF-kappaB inhibiting phaeophytins from the green alga Cladophora fascicularis.

Science.gov (United States)

Huang, Xinping; Li, Min; Xu, Bo; Zhu, Xiaobin; Deng, Zhiwei; Lin, Wenhan

2007-03-21

Chemical examination of the green alga Cladophora fascicularis resulted in the isolation and characterization of a new porphyrin derivative, porphyrinolactone (1), along with five known phaeophytins 2-6 and fourteen sterols and cycloartanes. The structure of 1 was determined on the basis of spectroscopic analyses and by comparison of its NMR data with those of known phaeophytins. Compounds 1-6 displayed moderate inhibition of tumor necrosis factor alpha (TNF-alpha) induced nuclear factor-kappaB (NF-kappaB) activation, while 2 and 4 displayed potential inhibitory activity toward proteasome chymotripsin-like activation. The primary structure-activity relationship was also discussed.

Blood Chemistry Reference Values for Free-Ranging Asiatic Black Bears ( Ursus thibetanus) by Season, Age, and Sex.

Science.gov (United States)

Yang, Jeong-Jin; Jeong, Dong-Hyuk; Lim, Yoon-Kyu

2018-04-19

Physiological characteristics, such as blood chemistry values, are valuable for evaluating the health of the animals. To our knowledge, these values have never been reported for the free-ranging Asiatic black bear ( Ursus thibetanus; ABB). Thus, 28 blood chemistry values from 50 free-ranging ABBs captured in Jirisan National Park, Republic of Korea, from 2005 to 2016 were evaluated. The aim of this study was to establish blood chemistry reference values for the free-ranging ABBs during both the hibernating and nonhibernating seasons. During hibernation, mean values of creatinine (CRE), total cholesterol, total protein (TP), albumin (ALB), triglycerides, and Mg were significantly higher than those during nonhibernation; however, mean values of blood urea nitrogen, urea nitrogen to creatinine (U/C) ratio, inorganic phosphorous (IP), aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, lactate dehydrogenase (LDH), high-density lipoprotein cholesterol, and alkaline phosphatase (ALP) were significantly lower. Age differences (young vs. adult) were found in IP, LDH, TP, and ALB values during hibernation and in the U/C ratio, Ca, IP, ALP, creatine kinase myocardial band, CRE, total bilirubin, and uric acid values during nonhibernation. However, there were no sex differences (male vs. female).

Effects of age and sedentary lifestyle on skeletal muscle NF-kappaB signaling in men.

Science.gov (United States)

Buford, Thomas W; Cooke, Matthew B; Manini, Todd M; Leeuwenburgh, Christiaan; Willoughby, Darryn S

2010-05-01

Nuclear factor kappa B (NF-kappaB) is a critical signaling molecule of disuse-induced skeletal muscle atrophy. However, few studies have carefully investigated whether similar pathways are modulated with physical activity and age. The present study examined lean mass, maximal force production, and skeletal muscle NF-kappaB signaling in 41 men categorized as sedentary (OS, N = 13, 63.85 +/- 6.59 year), physically active (OA, N = 14, 60.71 +/- 5.54 year), or young and sedentary (YS, N = 14, 21.35 +/- 3.84 year). Muscle tissue from the vastus lateralis was assayed for messenger RNA (mRNA) expression of the beta subunit of IkB kinase (IKKbeta), cytosolic protein content of phosphorylated inhibitor of kappa B alpha (pIKBalpha), and nuclear content of NF-kappaB subunits p50 and p65. When compared with YS, OS demonstrated age-related muscle atrophy and reduced isokinetic knee extension torque. Physical activity in older individuals preserved maximal isokinetic knee extension torque. OS muscle contained 50% more pIKBalpha than OA and 61% more pIKBalpha than YS. Furthermore, nuclear p65 was significantly elevated in OS compared with YS. OS muscle did not differ from either of the other two groups for nuclear p50 or for mRNA expression of IKKbeta. These results indicate that skeletal muscle content of nuclear-bound p65 is elevated by age in humans. The elevation in nuclear-bound p65 appears to be at least partially due to significant increases in pIKBalpha. A sedentary lifestyle appears to play some role in increased IKBalpha; however, further research is needed to identify downstream effects of this increase.

Lentiviral-mediated targeted NF-kappaB blockade in dorsal spinal cord glia attenuates sciatic nerve injury-induced neuropathic pain in the rat.

Science.gov (United States)

Meunier, Alice; Latrémolière, Alban; Dominguez, Elisa; Mauborgne, Annie; Philippe, Stéphanie; Hamon, Michel; Mallet, Jacques; Benoliel, Jean-Jacques; Pohl, Michel

2007-04-01

Neuropathic pain developing after peripheral nerve injury is associated with altered neuronal and glial cell functions in the spinal cord. Activated glia produces algogenic mediators, exacerbating pain. Among the different intracellular pathways possibly involved in the modified glial function, the nuclear factor kappaB (NF-kappaB) system is of particular interest, as numerous genes encoding inflammation- and pain-related molecules are controlled by this transcription factor. NF-kappaB is a pleiotropic factor also involved in central nervous system homeostasy. To study its role in chronic pain, it is thus essential to inhibit the NF-kappaB pathway selectively in activated spinal glial cells. Here, we show that when restricted to spinal cord and targeted to glial cells, lentiviral vector-mediated delivery of NF-kappaB super- repressor IkappaBalpha resulted in an inhibition of the NF-kappaB pathway activated in the rat spinal cord after sciatic nerve injury (chronic constriction injury, CCI). Concomitantly, IkappaBalpha overproduction prevented the enhanced expression of interleukin-6 and of inducible nitric oxide synthase associated with chronic constriction injury and resulted in prolonged antihyperalgesic and antiallodynic effects. These data show that targeted blockade of NF-kappaB activity in spinal glia efficiently alleviates pain behavior in CCI rats, demonstrating the active participation of the glial NF-kappaB pathway in the development of neuropathic pain after peripheral nerve injury.

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))

1992-02-26

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.

Ganoderma lucidum suppresses growth of breast cancer cells through the inhibition of Akt/NF-kappaB signaling.

Science.gov (United States)

Jiang, Jiahua; Slivova, Veronika; Harvey, Kevin; Valachovicova, Tatiana; Sliva, Daniel

2004-01-01

Ganoderma lucidum (Reishi, Lingzhi) is a popular Asian mushroom that has been used for more than 2 millennia for the general promotion of health and was therefore called the "Mushroom of Immortality." Ganoderma lucidum was also used in traditional Chinese medicine to prevent or treat a variety of diseases, including cancer. We previously demonstrated that Ganoderma lucidum suppresses the invasive behavior of breast cancer cells by inhibiting the transcription factor NF-kappaB. However, the molecular mechanisms responsible for the inhibitory effects of Ganoderma lucidum on the growth of highly invasive and metastatic breast cancer cells has not been fully elucidated. Here, we show that Ganoderma lucidum inhibits proliferation of breast cancer MDA-MB-231 cells by downregulating Akt/NF-kappaB signaling. Ganoderma lucidum suppresses phosphorylation of Akt on Ser473 and downregulates the expression of Akt, which results in the inhibition of NF-kappaB activity in MDA-MB-231 cells. The biological effect of Ganoderma lucidum was demonstrated by cell cycle arrest at G0/G1, which was the result of the downregulation of expression of NF-kappaB-regulated cyclin D1, followed by the inhibition of cdk4. Our results suggest that Ganoderma lucidum inhibits the growth of MDA-MB-231 breast cancer cells by modulating Akt/NF-kappaB signaling and could have potential therapeutic use for the treatment of breast cancer.

Hip strength and range of motion: Normal values from a professional football league.

Science.gov (United States)

Mosler, Andrea B; Crossley, Kay M; Thorborg, Kristian; Whiteley, Rod J; Weir, Adam; Serner, Andreas; Hölmich, Per

2017-04-01

To determine the normal profiles for hip strength and range of motion (ROM) in a professional football league in Qatar, and examine the effect of leg dominance, age, past history of injury, and ethnicity on these profiles. Cross-sectional cohort study. Participants included 394 asymptomatic, male professional football players, aged 18-40 years. Strength was measured using a hand held dynamometer with an eccentric test in side-lying for hip adduction and abduction, and the squeeze test in supine with 45° hip flexion. Range of motion measures included: hip internal and external rotation in 90° flexion, hip IR in prone, bent knee fall out and hip abduction in side-lying. Demographic information was collected and the effect on the profiles was analysed using linear mixed models with repeated measures. Strength values (mean±SD) were: adduction=3.0±0.6Nm/kg, abduction=2.6±0.4Nm/kg, adduction/abduction ratio=1.2±0.2, Squeeze test=3.6±0.8N/kg. Range of motion values: internal rotation in flexion=32±8°, external rotation=38±8°, internal rotation in prone=38±8°, bent knee fall out=13±4.4cm, abduction in side-lying=50±7.3°. Leg dominance had no clinically relevant effect on these profiles. Multivariate analysis demonstrated that age had a minor influence on squeeze strength (-0.03N/kg/year), external rotation (-0.30°/year) and abduction range (-0.19°/year) but past history of injury, and ethnicity did not. Normal values are documented for hip strength and range of motion that can be used as reference profiles in the clinical assessment, screening, and management of professional football players. Leg dominance, recent past injury history and ethnicity do not need to be accounted for when using these profiles for comparison purposes. Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

NF-kappaB specifically activates BMP-2 gene expression in growth plate chondrocytes in vivo and in a chondrocyte cell line in vitro.

Science.gov (United States)

Feng, Jian Q; Xing, Lianping; Zhang, Jiang-Hong; Zhao, Ming; Horn, Diane; Chan, Jeannie; Boyce, Brendan F; Harris, Stephen E; Mundy, Gregory R; Chen, Di

2003-08-01

Bone morphogenetic protein-2 (BMP-2) regulates growth plate chondrogenesis during development and postnatal bone growth, but the control mechanisms of BMP-2 expression in growth plate chondrocytes are unknown. Here we have used both in vitro and in vivo approaches to demonstrate that transcription factor, NF-kappaB, regulates BMP-2 gene expression in chondrocytes. Two putative NF-kappaB response elements were found in the -2712/+165 region of the BMP-2 gene. Cotransfection of mutant I-kappaBalpha expression plasmids with BMP-2 promoter-luciferase reporters into TMC-23 chondrocyte cell line suppressed BMP-2 transcription. Mutations in NF-kappaB response elements in the BMP-2 gene lead to decreases in BMP-2 promoter activity. Electrophoretic mobility shift assay using nuclear extracts from TMC-23 chondrocytic cells revealed that the NF-kappaB subunits p50 and p65 bound to the NF-kappaB response elements of the BMP-2 gene. Thus, NF-kappaB may positively regulate BMP-2 gene transcription. Consistent with these findings, expression of BMP-2 mRNA was significantly reduced in growth plate chondrocytes in NF-kappaB p50/p52 dKO mice, which associated with decreased numbers of 5-bromo-2'-deoxyuridine (BrdUrd)-positive cells in the proliferating zone of growth plate in these mice. Therefore, in postnatal growth plate chondrocytes, expression of BMP-2 is regulated by NF-kappaB, which may play an important role in chondrogenesis.

Consistent comparison of angle Kappa adjustment between Oculyzer and Topolyzer Vario topography guided LASIK for myopia by EX500 excimer laser.

Science.gov (United States)

Sun, Ming-Shen; Zhang, Li; Guo, Ning; Song, Yan-Zheng; Zhang, Feng-Ju

2018-01-01

To evaluate and compare the uniformity of angle Kappa adjustment between Oculyzer and Topolyzer Vario topography guided ablation of laser in situ keratomileusis (LASIK) by EX500 excimer laser for myopia. Totally 145 cases (290 consecutive eyes )with myopia received LASIK with a target of emmetropia. The ablation for 86 cases (172 eyes) was guided manually based on Oculyzer topography (study group), while the ablation for 59 cases (118 eyes) was guided automatically by Topolyzer Vario topography (control group). Measurement of adjustment values included data respectively in horizontal and vertical direction of cornea. Horizontally, synclastic adjustment between manually actual values (dx manu ) and Oculyzer topography guided data (dx ocu ) accounts 35.5% in study group, with mean dx manu /dx ocu of 0.78±0.48; while in control group, synclastic adjustment between automatically actual values (dx auto ) and Oculyzer topography data (dx ocu ) accounts 54.2%, with mean dx auto /dx ocu of 0.79±0.66. Vertically, synclastic adjustment between dy manu and dy ocu accounts 55.2% in study group, with mean dy manu /dy ocu of 0.61±0.42; while in control group, synclastic adjustment between dy auto and dy ocu accounts 66.1%, with mean dy auto /dy ocu of 0.66±0.65. There was no statistically significant difference in ratio of actual values/Oculyzer topography guided data in horizontal and vertical direction between two groups ( P =0.951, 0.621). There is high consistency in angle Kappa adjustment guided manually by Oculyzer and guided automatically by Topolyzer Vario topography during corneal refractive surgery by WaveLight EX500 excimer laser.

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

Energy Technology Data Exchange (ETDEWEB)

Sandi, C.; Borrell, J.; Guaza, C. (Cajal Institute, Madrid (Spain))

1990-01-01

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

The NF-kappa B inhibitor, celastrol, could enhance the anti-cancer effect of gambogic acid on oral squamous cell carcinoma

International Nuclear Information System (INIS)

He, Di; Chen, Wantao; Xu, Qin; Yan, Ming; Zhang, Ping; Zhou, Xiaojian; Zhang, Zhiyuan; Duan, Wenhu; Zhong, Laiping; Ye, Dongxia

2009-01-01

Gambogic acid (GA) is a major active ingredient of gamboge, a widely used traditional Chinese medicine that has been reported to be a potent cytotoxic agent against some malignant tumors. Many studies have shown that the NF-kappa B signaling pathway plays an important role in anti-apoptosis and the drug resistance of tumor cells during chemotherapy. In this study, the effects and mechanisms of GA and the NF-kappa B inhibitor celastrol on oral cancer cells were investigated. Three human oral squamous cell carcinoma cell lines, Tca8113, TSCC and NT, were treated with GA alone, celastrol alone or GA plus celastrol. Cytotoxicity was assessed by MTT assay. The rate of apoptosis was examined with annexin V/PI staining as well as transmission electronic microscopy in Tca8113 cells. The level of constitutive NF-kappa B activity in oral squamous cell carcinoma cell lines was determined by immunofluorescence assays and nuclear extracts and electrophoretic mobility shift assays (EMSAs) in vitro. To further investigate the role of NF-kappa B activity in GA and celastrol treatment in oral squamous cell carcinoma, we used the dominant negative mutant SR-IκBα to inhibit NF-kappa B activity and to observe its influence on the effect of GA. The results showed that GA could inhibit the proliferation and induce the apoptosis of the oral squamous cell carcinoma cell lines and that the NF-kappa B pathway was simultaneously activated by GA treatment. The minimal cytotoxic dose of celastrol was able to effectively suppress the GA-induced NF-kappa B pathway activation. Following the combined treatment with GA and the minimal cytotoxic dose of celastrol or the dominant negative mutant SR-IκBα, proliferation was significantly inhibited, and the apoptotic rate of Tca8113 cells was significantly increased. The combination of GA and celastrol has a synergistic antitumor effect. The effect can be primarily attributed to apoptosis induced by a decrease in NF-kappa B pathway activation. The

SIRT1 overexpression decreases cisplatin-induced acetylation of NF-{kappa}B p65 subunit and cytotoxicity in renal proximal tubule cells

Energy Technology Data Exchange (ETDEWEB)

Jung, Yu Jin; Lee, Jung Eun; Lee, Ae Sin [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Kang, Kyung Pyo; Lee, Sik; Park, Sung Kwang [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Lee, Sang Yong [Department of Diagnostic Radiology, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Han, Myung Kwan [Department of Microbiology, Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Kim, Duk Hoon [Division of Forensic Medicine, National Forensic Service, Seoul (Korea, Republic of); Kim, Won, E-mail: kwon@jbnu.ac.kr [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju (Korea, Republic of)

2012-03-09

Highlights: Black-Right-Pointing-Pointer Cisplatin increases acetylation of NF-{kappa}B p65 subunit in HK2 cells. Black-Right-Pointing-Pointer SIRT1 overexpression decreases cisplatin-induced p65 acetylation and -cytotoxicity. Black-Right-Pointing-Pointer Resveratrol decreased cisplatin-induced cell viability through deacetylation of p65. -- Abstract: As the increased acetylation of p65 is linked to nuclear factor-{kappa}B (NF-{kappa}B) activation, the regulation of p65 acetylation can be a potential target for the treatment of inflammatory injury. Cisplatin-induced nephrotoxicity is an important issue in chemotherapy of cancer patients. SIRT1, nicotinamide adenine dinucleotide (NAD{sup +})-dependent protein deacetylase, has been implicated in a variety of cellular processes such as inflammatory injury and the control of multidrug resistance in cancer. However, there is no report on the effect of SIRT1 overexpression on cisplatin-induced acetylation of p65 subunit of NF-{kappa}B and cell injury. To investigate the effect of SIRT1 in on cisplatin-induced acetylation of p65 subunit of NF-{kappa}B and cell injury, HK2 cells were exposed with SIRT1 overexpression, LacZ adenovirus or dominant negative adenovirus after treatment with cisplatin. While protein expression of SIRT1 was decreased by cisplatin treatment compared with control buffer treatment, acetylation of NF-{kappa}B p65 subunit was significantly increased after treatment with cisplatin. Overexpression of SIRT1 ameliorated the increased acetylation of p65 of NF-{kappa}B during cisplatin treatment and cisplatin-induced cytotoxicity. Further, treatment of cisplatin-treated HK2 cells with resveratrol, a SIRT1 activator, also decreased acetylation of NF-{kappa}B p65 subunit and cisplatin-induced increase of the cell viability in HK2 cells. Our findings suggests that the regulation of acetylation of p65 of NF-{kappa}B through SIRT1 can be a possible target to attenuate cisplatin-induced renal cell damage.

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

Science.gov (United States)

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

1980-01-01

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

Behavioral meaningful opioidergic stimulation activates kappa receptor gene expression

International Nuclear Information System (INIS)

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

2012-01-01

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

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)

2012-06-01

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

Localized Gastric Amyloidosis with Kappa and Lambda Light Chain Co-Expression

Directory of Open Access Journals (Sweden)

Yong Hwan Ahn

2018-05-01

Full Text Available Esophagogastroduodenoscopy for cancer screening was performed in a 55-year-old woman as part of a health screening program, and revealed a depressed lesion approximately 20 mm in diameter in the lesser curvature of the mid-gastric body. Several biopsy specimens were collected as the lesion resembled early gastric cancer; however, histopathologic evaluation revealed chronic active gastritis with an ulcer and amorphous eosinophilic material deposition. Congo red staining identified amyloid proteins, and apple-green birefringence was shown using polarized light microscopy. Immunohistochemical staining revealed the presence of kappa and lambda chain-positive plasma cells. There was no evidence of underlying plasma cell dyscrasia or amyloid deposition in other segments of the gastrointestinal tract. Echocardiography and computed tomography of the chest, abdomen, and pelvis did not show any significant findings. Thus, the patient was diagnosed with localized gastric amyloidosis with kappa and lambda light chain coexpression.

Tumour Necrosis Factor-alpha and Nuclear Factor-kappa B Gene Variants in Sepsis.

Science.gov (United States)

Acar, Leyla; Atalan, Nazan; Karagedik, E Hande; Ergen, Arzu

2018-01-20

The humoral system is activated and various cytokines are released due to infections in tissues and traumatic damage. Nuclear factor-kappa B dimers are encoded by nuclear factor-kappa B genes and regulate transcription of several crucial proteins of inflammation such as tumour necrosis factor-alpha. To investigate the possible effect of polymorphisms on tumour necrosis factor-alpha serum levels with clinical and prognostic parameters of sepsis by determining the nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A) gene polymorphisms and tumour necrosis factor-alpha serum levels. Case-control study. Seventy-two patients with sepsis and 104 healthy controls were included in the study. In order to determine the polymorphisms of nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A), polymerase chain reaction-restriction fragment length polymorphism analysis was performed and serum tumour necrosis factor-alpha levels were determined using an enzyme-linked immunosorbent assay. We observed no significant differences in tumour necrosis factor-alpha serum levels between the study groups. In the patient group, an increase in the tumour necrosis factor-alpha serum levels in patients carrying the tumour necrosis factor-alpha (-308 G/A) A allele compared to those without the A allele was found to be statistically significant. Additionally, an increase in the tumour necrosis factor-alpha serum levels in patients carrying tumour necrosis factor-alpha (-308 G/A) AA genotype compared with patients carrying the AG or GG genotypes was statistically significant. No significant differences were found in these 2 polymorphisms between the patient and control groups (p>0.05). Our results showed the AA genotype and the A allele of the tumour necrosis factor-alpha (-308 G/A) polymorphism may be used as a predictor of elevated tumour necrosis factor-alpha levels in patients with sepsis.

Koefesien Kappa sebagai Indeks Kesepakatan Hasil Diognosis Mikroskopis Malaria di Kabupaten Belu Nusa Tenggara Timur

Directory of Open Access Journals (Sweden)

Fridolina Mau

2015-07-01

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

Understanding the connection between historic range of variation, current social values and developing desired conditions

Science.gov (United States)

Larry Blocker; Susan K. Hagle; Rick Lasko; Robert Keane; Barry Bollenbacher; Bruce Fox; Fred Samson; Randy Gay; Cynthia Manning

2001-01-01

Relationships between the development of desired conditions based on today’s social values, and an understanding of the historic range of variability (HRV) are key to the implementation of ecosystem management. Relevant to the discussion are wildlife habitat values, forage production, economics related to wood resources, aesthetics and visual quality, changes in...

$\\kappa$-Minkowski star product in any dimension from symplectic realization

OpenAIRE

Pachol, Anna; Vitale, Patrizia

2015-01-01

We derive an explicit expression for the star product reproducing the $\\kappa$-Minkowski Lie algebra in any dimension $n$. The result is obtained by suitably reducing the Wick-Voros star product defined on $\\mathbb{C}^{d}_\\theta$ with $n=d+1$. It is thus shown that the new star product can be obtained from a Jordanian twist.

Low Frequency Electrostatic Waves in Weakly Inhomogeneous Magnetoplasma Modeled by Lorentzian (kappa) Distributions

National Research Council Canada - National Science Library

Basu, Bamandas

2008-01-01

... (to the ambient magnetic field) flow velocities associated with the current. In order to illustrate the distinguishing features of the kappa distributions, stability properties of the low frequency...

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

Science.gov (United States)

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

2003-01-01

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

Experimental study on the effects of recombinant adenoviral-mediated mI{kappa}B{alpha} gene combined with irradiation on the treatment of hepatocarcinoma

Energy Technology Data Exchange (ETDEWEB)

Kejun, Zhang; Dechun, Li; Dongming, Zhu [The First Affiliated Hospital to Suzhou Univ., Suzhou (China); Caixia, Song

2007-10-15

Objective: To explore the effect of recombinant adenovirus vector mediated mutant I{kappa}B{alpha} (mI{kappa}B{alpha}) combined with radiation on the hepatocarcinoma. Methods: Limited dilution method was used to test the virus titer in 293 cells. The HCC9204 cells were infected with MOI 10,20,30 and 50 for 48 h, respectively. The expression of p65 and mI{kappa}B{alpha} protein was analyzed by Western blot. Transfected HCC9204 cells and controls were treated with 4 Gy {gamma} rays. The inhibition rate of HCC9204 cells was examined by MTT. Rat models of HCC9204 was constructed. AdmI{kappa}B{alpha} plasmids were injected into tumor tissue and the tumors were administered with 6 Gy {gamma} irradiation 48 hours later. Tumor growth at different time points was recorded during 28 days. Results: The titer of AdmI{kappa}B{alpha} is 1.252 x 10{sup 9} pfu/ml. The expression of mI{kappa}B{alpha} protein was increased with titer of AdmI{kappa}B{alpha}, and p65 protein began to decrease when MOI was 10, and reached the lowest when MOI was 50, they were all dose-dependent. The proliferation of HCC9204 cell lines were suppressed, as was more significant combined with radiation, and the effect was in a viral dose-dependent manner. From days 7 to 28 after AdmI{kappa}B{alpha} gene and radiotherapy, the tumor growth was significantly slower than after irradiation or gene therapy alone. Conclusions: Recombinant adenoviral-mediated mI{kappa}B{alpha} gene, combined with irradiation, can increase the cell-killing effect. It is better than that of either one alone. (authors)

Prognostic value of the serum free light chain ratio in newly diagnosed myeloma: proposed incorporation into the international staging system.

Science.gov (United States)

Snozek, C L H; Katzmann, J A; Kyle, R A; Dispenzieri, A; Larson, D R; Therneau, T M; Melton, L J; Kumar, S; Greipp, P R; Clark, R J; Rajkumar, S V

2008-10-01

To determine if the serum free light chain (FLC) ratio has prognostic value in patients with symptomatic multiple myeloma (MM), baseline serum samples from a well-characterized cohort of 790 newly diagnosed MM patients were tested with the FLC assay. FLC ratio was calculated as kappa/lambda (reference range 0.26-1.65). On the basis of the distribution of values, a cutpoint kappa/lambda FLC ratio of 32 was chosen for further analysis. Overall survival was significantly inferior in patients with an abnormal FLC ratio of 32 (n=479) compared with those with an FLC ratio between 0.03 and 32 (n=311), with median survival of 30 versus 39 months, respectively. We incorporated abnormal FLC ratio with the International Staging System (ISS) risk factors (that is, albumin or=3.5 g/l), to create a risk stratification model with improved prognostic capabilities. Patients with 0, 1, 2 or 3 adverse risk factors had significantly different overall survival, with median survival times of 51, 39, 30 and 22 months, respectively (P<0.001). These findings suggest that the serum FLC ratio at initial diagnosis is an important predictor of prognosis in myeloma, and can be incorporated into the ISS for improved risk stratification.

NF-kappaB is involved in SHetA2 circumvention of TNF-alpha resistance, but not induction of intrinsic apoptosis.

Science.gov (United States)

Chengedza, Shylet; Benbrook, Doris Mangiaracina

2010-03-01

Treatment of cancer with tumor necrosis factor-alpha (TNF-alpha) is hindered by resistance and toxicity. The flexible heteroarotinoid, SHetA2, sensitizes resistant ovarian cancer cells to TNF-alpha-induced extrinsic apoptosis, and also induces intrinsic apoptosis as a single agent. This study tested the hypothesis that nuclear factor-kappaB (NF-kappaB) is involved in SHetA2-regulated intrinsic and extrinsic apoptosis. SHetA2 inhibited basal and TNF-alpha-induced or hydrogen peroxide-induced NF-kappaB activity through counter-regulation of upstream kinase (IkappaB kinase) activity, inhibitor protein (IkappaB-alpha) phosphorylation, and p-65 NF-kappaB subunit nuclear translocation, but independently of reactive oxygen species generation. Ectopic over-expression of p-65, or treatment with TNF-alpha receptor 1 (TNFR1) small interfering RNA or a caspase-8 inhibitor, each attenuated synergistic apoptosis by SHetA2 and TNF-alpha, but did not affect intrinsic apoptosis caused by SHetA2. In conclusion, NF-kappaB repression is involved in SHetA2 circumvention of resistance to TNF-alpha-induced extrinsic apoptosis, but not in SHetA2 induction of intrinsic apoptosis.

Enantioselective kappa opioid binding sites on the macrophage cell line, P388d sub 1

Energy Technology Data Exchange (ETDEWEB)

Carr, D.J.J.; Blalock, J.E. (Univ. of Alabama, Birmingham (USA)); DeCosta, B.R.; Jacobson, A.E.; Rice, K.C. (NIDDK, NIH, Bethesda, MD (USA))

1991-01-01

A kappa opioid binding site has been characterized on the macrophage cell line, P388d{sub 1}, using the kappa selective affinity ligand, ({sup 3H}(1S,2S)-(-)-trans-2-isothiocyanato-N-methyl-N-(2-(1-phrrolidinyl) cyclohexyl) benzeneacetamide ((-)BD166). The kappa site has a relative molecular mass (Mr) of 38,000 under nonreducing conditions and 42,000 under reducing conditions. Moreover, it exhibits enantioselectivity in that 1S,2S-(-)-trans-3,4-dichloro-N-methyl-N-(2-(1-pyrrolidinyl)cyclohexyl) benzeneacetamide ((-)-U-50,488) blocks ({sup 3}H)95{alpha},7{alpha},8{beta})-(-)-N-methyl-N-(7-(1- pyrrolidinyl)-1-oxaspiro-(4,5)-dec-8-yl)benzeneacetamide (U-69,593) binding to P388d{sub 1} cells with an IC{sub 50} = 7.0 nM whereas 1R,2R-(+)-trans-3,4-dichloro-N-methyl-N-(2-(1-pyrrolidinyl)cyclohexyl) benzeneacetamide ((+)U-50,488) blocks ({sup 3}H)U-69,593 binding to P388d{sub 1} cells with an IC{sub 50} = 700 nM.

Increased synovial tissue NF-kappa B1 expression at sites adjacent to the cartilage-pannus junction in rheumatoid arthritis.

NARCIS (Netherlands)

Benito, M.J.; Murphy, E.P.; Berg, W.B. van den; Fitzgerald, O.; Bresnihan, B.

2004-01-01

OBJECTIVE: To compare the expression of the Rel/NF-kappa B subunits, NF-kappa B1 (p50) and RelA (p65), in paired synovial tissue samples selected from sites adjacent to and remote from the cartilage-pannus junction (CPJ) in patients with inflammatory arthritis. METHODS: Synovial tissue was selected

Nutritive value of the Range Plants in the Western Mediterranean Desert of Egypt

International Nuclear Information System (INIS)

El-Din, A.S.; El-Kady, H.F.

2001-01-01

The present study assesses the nutritive value of the range plants in the Western Mediterranean Desert of Egypt to evaluate their usage as forage for domestic animals (mainly sheep and goats). Analysis of plant organs which represent the diet selected by the herbivores indicated that their mean protein content is about 1.1%. This is lower than the proper level, but it is ranked as acceptable protein content. The average digestible protein intake was about 46.4g 100kg live weight-1 day-1, which is inadequate for the protein needs of grazing animals. The amount of total digestible nutrient (TDN) was also lower than the normal requirements of the sheep. The shortfall in the forage nutrition may be attributed to the high stocking rate. If the stocking rate is about seven times lower than the present value, most of the requirements of energy and protein could be fulfilled in the range. The ratio of Ca: P was higher than the optimum, which may lead to lower utilization of both Ca and P by animals. (author)

Selective kappa-opioid agonists: synthesis and structure-activity relationships of piperidines incorporating on oxo-containing acyl group.

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Giardina, G; Clarke, G D; Dondio, G; Petrone, G; Sbacchi, M; Vecchietti, V

1994-10-14

This study describes the synthesis and the structure-activity relationships (SARs) of the (S)-(-)-enantiomers of a novel class of 2-(aminomethyl)piperidine derivatives, using kappa-opioid binding affinity and antinociceptive potency as the indices of biological activity. Compounds incorporating the 1-tetralon-6-ylacetyl residue (30 and 34-45) demonstrated an in vivo antinociceptive activity greater than predicted on the basis of their kappa-binding affinities. In particular, (2S)-2-[(dimethylamino)methyl]-1-[(5,6,7,8-tetrahydro-5-oxo-2- naphthyl)acetyl]piperidine (34) was found to have a potency similar to spiradoline in animal models of antinociception after subcutaneous administration, with ED50s of 0.47 and 0.73 mumol/kg in the mouse and in the rat abdominal constriction tests, respectively. Further in vivo studies in mice and/or rats revealed that compound 34, compared to other selective kappa-agonists, has a reduced propensity to cause a number of kappa-related side effects, including locomotor impairment/sedation and diuresis, at antinociceptive doses. For example, it has an ED50 of 26.5 mumol/kg sc in the rat rotarod model, exhibiting a ratio of locomotor impairment/sedation vs analgesia of 36. Possible reasons for this differential activity and its clinical consequence are discussed.

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

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

2003-10-01

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

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

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Martinović, M.

2017-12-01

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

The Problems with the Kappa Statistic as a Metric of Interobserver Agreement on Lesion Detection Using a Third-reader Approach When Locations Are Not Prespecified.

Science.gov (United States)

Shih, Joanna H; Greer, Matthew D; Turkbey, Baris

2018-03-16

To point out the problems with Cohen kappa statistic and to explore alternative metrics to determine interobserver agreement on lesion detection when locations are not prespecified. Use of kappa and two alternative methods, namely index of specific agreement (ISA) and modified kappa, for measuring interobserver agreement on the location of detected lesions are presented. These indices of agreement are illustrated by application to a retrospective multireader study in which nine readers detected and scored prostate cancer lesions in 163 consecutive patients (n = 110 cases, n = 53 controls) using the guideline of Prostate Imaging Reporting and Data System version 2 on multiparametric magnetic resonance imaging. The proposed modified kappa, which properly corrects for the amount of agreement by chance, is shown to be approximately equivalent to the ISA. In the prostate cancer data, average kappa, modified kappa, and ISA equaled 30%, 55%, and 57%, respectively, for all lesions and 20%, 87%, and 87%, respectively, for index lesions. The application of kappa could result in a substantial downward bias in reader agreement on lesion detection when locations are not prespecified. ISA is recommended for assessment of reader agreement on lesion detection. Published by Elsevier Inc.

Non-small-cell lung cancer resectability: diagnostic value of PET/MR

International Nuclear Information System (INIS)

Fraioli, Francesco; Menezes, Leon; Kayani, Irfan; Syed, Rizwan; O'Meara, Celia; Barnes, Anna; Bomanji, Jamshed B.; Punwani, Shonit; Groves, Ashley M.; Screaton, Nicholas J.; Janes, Samuel M.; Win, Thida; Zaccagna, Fulvio

2015-01-01

To assess the diagnostic performance of PET/MR in patients with non-small-cell lung cancer. Fifty consecutive consenting patients who underwent routine 18 F-FDG PET/CT for potentially radically treatable lung cancer following a staging CT scan were recruited for PET/MR imaging on the same day. Two experienced readers, unaware of the results with the other modalities, interpreted the PET/MR images independently. Discordances were resolved in consensus. PET/MR TNM staging was compared to surgical staging from thoracotomy as the reference standard in 33 patients. In the remaining 17 nonsurgical patients, TNM was determined based on histology from biopsy, imaging results (CT and PET/CT) and follow-up. ROC curve analysis was used to assess accuracy, sensitivity and specificity of the PET/MR in assessing the surgical resectability of primary tumour. The kappa statistic was used to assess interobserver agreement in the PET/MR TNM staging. Two different readers, without knowledge of the PET/MR findings, subsequently separately reviewed the PET/CT images for TNM staging. The generalized kappa statistic was used to determine intermodality agreement between PET/CT and PET/MR for TNM staging. ROC curve analysis showed that PET/MR had a specificity of 92.3 % and a sensitivity of 97.3 % in the determination of resectability with an AUC of 0.95. Interobserver agreement in PET/MR reading ranged from substantial to perfect between the two readers (Cohen's kappa 0.646 - 1) for T stage, N stage and M stage. Intermodality agreement between PET/CT and PET/MR ranged from substantial to almost perfect for T stage, N stage and M stage (Cohen's kappa 0.627 - 0.823). In lung cancer patients PET/MR appears to be a robust technique for preoperative staging. (orig.)

Agreement of dietary fiber and calorie intake values according to the choice of nutrient composition and household measure tables

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Michele DREHMER

Full Text Available ABSTRACT Objective: To analyze the variations in the daily intake of dietary fiber and calories according to the different nutrient composition and homemade measure tables. Methods: Five different methods based on different nutrient composition and household measure tables were used to calculate daily calorie and fiber intake, measured using a food frequency questionnaire, of 633 pregnant women receiving care in primary health care units in the Southern region of Brazil; they were selected to participate in a cohort study. The agreement between the five methods was evaluated using the Kappa and weighted Kappa coefficients. The Nutritional Support Table, a Brazilian traditional food composition table and the Brazilian household expenditure survey were used in Method 1. Brazilian Food Composition Table and the Table for the Assessment of Household Measures (Pinheiro were used in Methods 2 and 3. The average values of all subtypes of food listed in the Brazilian Food Composition Table for each corresponding item in the food frequency questionnaire were calculated in the method 3. The United States Department of Agriculture Food Composition Table and the table complied by Pinheiro were used in Method 4. The Brazilian Food Composition Table and the Brazilian household expenditure survey were used in Method 5. Results: The highest agreement of calorie intake values were found between Methods 2 and 3 (Kappa=0.94; 0.92-0.95, and the lowest agreement was found between Methods 4 and 5 (Kappa=0.46; 0.42-0.50. As for the fiber intake, the highest agreement was found between Methods 2 and 5 (Kappa=0.87; 0.82-0.90, and the lowest agreement was observed between Methods 1 and 4 (Kappa=0.36; 0.3-0.43. Conclusion: Considerable differences were found between the nutritional composition tables. Therefore, the choice of the table can influence the comparability between studies.

Quantitative analysis of multiple kappa-opioid receptors by selective and nonselective ligand binding in guinea pig spinal cord: Resolution of high and low affinity states of the kappa 2 receptors by a computerized model-fitting technique

International Nuclear Information System (INIS)

Tiberi, M.; Magnan, J.

1990-01-01

The binding characteristics of selective and nonselective opioids have been studied in whole guinea pig spinal cord, using a computer fitting method to analyze the data obtained from saturation and competition studies. The delineation of specific binding sites labeled by the mu-selective opioid [3H]D-Ala2,MePhe4,Gly-ol5-enkephalin (Kd = 2.58 nM, R = 4.52 pmol/g of tissue) and by the delta-selective opioid [3H]D-Pen2, D-Pen5-enkephalin (Kd = 2.02 nM, R = 1.47 pmol/g of tissue) suggests the presence of mu and delta-receptors in the spinal cord tissue. The presence of kappa receptors was probed by the kappa-selective opioid [3H]U69593 (Kd = 3.31 nM, R = 2.00 pmol/g of tissue). The pharmacological characterization of the sites labeled by [3H]U69593 confirms the assumption that this ligand discriminates kappa receptors in guinea pig spinal cord. The benzomorphan [3H]ethylketazocine labels a population of receptors with one homogeneous affinity state (Kd = 0.65 nM, R = 7.39 pmol/g of tissue). The total binding capacity of this ligand was not different from the sum of the binding capacities of mu, delta-, and kappa-selective ligands. Under mu- and delta-suppressed conditions, [3H]ethylketazocine still binds to receptors with one homogeneous affinity state (Kd = 0.45 nM, R = 1.69 pmol/g of tissue). Competition studies performed against the binding of [3H]ethylketazocine under these experimental conditions reveal that the pharmacological profile of the radiolabeled receptors is similar to the profile of the kappa receptors labeled with [3H]U69593. Saturation studies using the nonselective opioid [3H]bremazocine demonstrate that this ligand binds to spinal cord membranes with heterogeneous affinities (Kd1 = 0.28 nM, R1 = 7.91 pmol/g of tissue; Kd2 = 3.24 nM, R2 = 11.2 pmol/g of tissue)

Quantitative analysis of multiple kappa-opioid receptors by selective and nonselective ligand binding in guinea pig spinal cord: Resolution of high and low affinity states of the kappa 2 receptors by a computerized model-fitting technique

Energy Technology Data Exchange (ETDEWEB)

Tiberi, M.; Magnan, J. (Universite de Montreal, Quebec (Canada))

1990-05-01

The binding characteristics of selective and nonselective opioids have been studied in whole guinea pig spinal cord, using a computer fitting method to analyze the data obtained from saturation and competition studies. The delineation of specific binding sites labeled by the mu-selective opioid (3H)D-Ala2,MePhe4,Gly-ol5-enkephalin (Kd = 2.58 nM, R = 4.52 pmol/g of tissue) and by the delta-selective opioid (3H)D-Pen2, D-Pen5-enkephalin (Kd = 2.02 nM, R = 1.47 pmol/g of tissue) suggests the presence of mu and delta-receptors in the spinal cord tissue. The presence of kappa receptors was probed by the kappa-selective opioid (3H)U69593 (Kd = 3.31 nM, R = 2.00 pmol/g of tissue). The pharmacological characterization of the sites labeled by (3H)U69593 confirms the assumption that this ligand discriminates kappa receptors in guinea pig spinal cord. The benzomorphan (3H)ethylketazocine labels a population of receptors with one homogeneous affinity state (Kd = 0.65 nM, R = 7.39 pmol/g of tissue). The total binding capacity of this ligand was not different from the sum of the binding capacities of mu, delta-, and kappa-selective ligands. Under mu- and delta-suppressed conditions, (3H)ethylketazocine still binds to receptors with one homogeneous affinity state (Kd = 0.45 nM, R = 1.69 pmol/g of tissue). Competition studies performed against the binding of (3H)ethylketazocine under these experimental conditions reveal that the pharmacological profile of the radiolabeled receptors is similar to the profile of the kappa receptors labeled with (3H)U69593. Saturation studies using the nonselective opioid (3H)bremazocine demonstrate that this ligand binds to spinal cord membranes with heterogeneous affinities (Kd1 = 0.28 nM, R1 = 7.91 pmol/g of tissue; Kd2 = 3.24 nM, R2 = 11.2 pmol/g of tissue).

Protective protein/cathepsin A down-regulates osteoclastogenesis by associating with and degrading NF-kappaB p50/p65.

Science.gov (United States)

Masuhara, Masaaki; Sato, Takuya; Hada, Naoto; Hakeda, Yoshiyuki

2009-01-01

Disruption of the cooperative function balance between osteoblasts and osteoclasts causes various bone disorders, some of which are attributed to abnormal osteoclast recruitment. Osteoclast differentiation is dependent on the receptor activator of nuclear factor (NF)-kappaB ligand (RANKL) as well as the macrophage colony-stimulating factor. The osteoclast formation induced by cytokines requires activation of NF-kappaB, AP-1 and nuclear factor of activated T cells c1. However, osteoclasts are not the only cell types that express these transcription factors, suggesting that some unknown molecules specific for osteoclasts may associate with the transcription factors. Here, we explored the possibility of molecules binding directly to NF-kappaB and cloned protective protein/cathepsin A (PPCA) by yeast two-hybrid screening using a cDNA library of osteoclast precursors. Forced expression of PPCA with p50/p65 in HEK293 cells decreased both the level of p50/p65 proteins and the transcriptional activity. Abundant PPCA was detected in the lysosomes of the transfected HEK293 cells, but a small amount of this enzyme was also present in the cytosolic fraction. In addition, over-expression of PPCA caused the disappearance of p50/p65 in both the lysosomal and cytosolic fractions. PPCA was expressed throughout osteoclastogenesis, and the expression was slightly up-regulated by RANKL signaling. Knockdown of PPCA in osteoclast precursors with PPCA siRNA stimulated binding of nuclear proteins to oligonucleotides containing an NF-kappaB binding motif and increased osteoclastogenesis. Our present results indicate a novel role for PPCA in osteoclastogenesis via down-regulation of NF-kappaB activity and suggest a new function for PPCA as an NF-kappaB-degrading enzyme in addition to its known multifunctional properties.

Bacterial effector binding to ribosomal protein s3 subverts NF-kappaB function.

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Xiaofei Gao

2009-12-01

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

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)

2011-07-01

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.

Classification of intertrochanteric fractures with computed tomography: a study of intraobserver and interobserver variability and prognostic value.

Science.gov (United States)

Chapman, Cary B; Herrera, Mauricio F; Binenbaum, Gil; Schweppe, Michael; Staron, Ronald B; Feldman, Frieda; Rosenwasser, Melvin P

2003-09-01

The purpose of this prospective study was to determine the level of interobserver and intraobserver agreement among orthopedic surgeons and radiologists when computed tomography (CT) scans are used with plain radiographs to evaluate intertrochanteric fractures. In addition, the prognostic value of current classifications systems concerning quality of life was evaluated. Sixty-one patients who presented with intertrochanteric fractures received open reduction and internal fixation with compression hip screw. Three orthopedic surgeons and 2 radiologists independently classified the fractures according to 2 systems: Evans-Jensen and AO (Arbeitsgemeinschaft für Osteo-synthesefragen). Fractures were initially graded with plain radiographs and then again in conjunction with CT. Results were analyzed using the (kappa) kappa coefficient. The 36-item Short-Form Health Survey was administered at baseline, 3 months, and 1 year, and results were correlated with fracture grade. Mean kappa coefficients when comparing radiography alone with radiography and CT scan were 0.63 for the AO system and 0.59 for the Evans-Jensen system. Both represent "fair" agreements. Mean overall interobserver kappa coefficients were 0.67 for radiologists and 0.57 for orthopedic surgeons. Radiologists also had higher intraobserver kappa coefficients. No significant relationships were found between follow-up Short Form Health Survey results and intraoperative grading of fractures. When these classification schemes are compared, interobserver agreement does not appear to change dramatically when information from CT scans is added. This may suggest that (1) more data have been provided by CT with greater possibilities for misinterpretation and (2) these classification schemes may not be comprehensive in describing fracture pattern and displacement. Finally, both systems failed to provide any prognostic value.

Lactobacillus rhamnosus GR-1 enhances NF-kappaB activation in Escherichia coli-stimulated urinary bladder cells through TLR4

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Karlsson Mattias

2012-01-01

Full Text Available Abstract Background Epithelial cells of the urinary tract recognize pathogenic bacteria through pattern recognition receptors on their surface, such as toll-like receptors (TLRs, and mount an immune response through the activation of the NF-kappaB pathway. Some uropathogenic bacteria can subvert these cellular responses, creating problems with how the host eliminates pathogens. Lactobacillus is a genus of lactic acid bacteria that are part of the microbiota and consist of many probiotic strains, some specifically for urogenital infections. Immunomodulation has emerged as an important mode of action of probiotic and commensal lactobacilli and given the importance of epithelial cells, we evaluated the effect of the urogenital probiotic Lactobacillus rhamnosus GR-1 on epithelial immune activation. Results Immune activation through the NF-kappaB pathway was initiated by stimulation of T24 urothelial cells with heat-killed Escherichia coli and this was further potentiated when cells were co-cultured with live L. rhamnosus GR-1. Heat-killed lactobacilli were poor activators of NF-kappaB. Concomitant stimulation of bladder cells with E. coli and L. rhamnosus GR-1 increased the levels of the pro-inflammatory cytokine TNF, whereas IL-6 and CXCL8 levels were reduced. Another probiotic, L. rhamnosus GG, was also able to potentiate NF-kappaB in these cells although at a significantly reduced level compared to the GR-1 strain. The transcript numbers and protein levels of the lipopolysaccharide receptor TLR4 were significantly increased after co-stimulation with E. coli and lactobacilli compared to controls. Furthermore, inhibition of TLR4 activation by polymixin B completely blocked the lactobacilli potentiation of NF-kappaB. Conclusions The immunological outcome of E. coli challenge of bladder cells was influenced by probiotic L. rhamnosus GR-1, by enhancing the activation of NF-kappaB and TNF release. Thus the urogenital probiotic L. rhamnosus GR-1

The formation of kappa-distribution accelerated electron populations in solar flares

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Bian, Nicolas H.; Stackhouse, Duncan J.; Kontar, Eduard P. [School of Physics and Astronomy, University of Glasgow, Glasgow G12 8QQ (United Kingdom); Emslie, A. Gordon, E-mail: n.bian@physics.gla.ac.uk, E-mail: d.stackhouse.1@research.gla.ac.uk, E-mail: eduard@astro.gla.ac.uk, E-mail: emslieg@wku.edu [Department of Physics and Astronomy, Western Kentucky University, Bowling Green, KY 42101 (United States)

2014-12-01

Driven by recent RHESSI observations of confined loop-top hard X-ray sources in solar flares, we consider stochastic acceleration of electrons in the presence of Coulomb collisions. If electron escape from the acceleration region can be neglected, the electron distribution function is determined by a balance between diffusive acceleration and collisions. Such a scenario admits a stationary solution for the electron distribution function that takes the form of a kappa distribution. We show that the evolution toward this kappa distribution involves a 'wave front' propagating forward in velocity space, so that electrons of higher energy are accelerated later; the acceleration timescales with energy according to τ{sub acc} ∼ E {sup 3/2}. At sufficiently high energies escape from the finite-length acceleration region will eventually dominate. For such energies, the electron velocity distribution function is obtained by solving a time-dependent Fokker-Planck equation in the 'leaky-box' approximation. Solutions are obtained in the limit of a small escape rate from an acceleration region that can effectively be considered a thick target.

Transforming growth factor-beta 1 (TGF-beta1) promotes IL-2 mRNA expression through the up-regulation of NF-kappaB, AP-1 and NF-AT in EL4 cells.

Science.gov (United States)

Han, S H; Yea, S S; Jeon, Y J; Yang, K H; Kaminski, N E

1998-12-01

Transforming growth factor beta1 (TGF-beta1) has been previously shown to modulate interleukin 2 (IL-2) secretion by activated T-cells. In the present studies, we determined that TGF-beta1 induced IL-2 mRNA expression in the murine T-cell line EL4, in the absence of other stimuli. IL-2 mRNA expression was significantly induced by TGF-beta1 (0.1-1 ng/ml) over a relatively narrow concentration range, which led to the induction of IL-2 secretion. Under identical condition, we examined the effect of TGF-beta1 on the activity of nuclear factor AT (NF-AT), nuclear factor kappaB (NF-kappaB), activator protein-1 (AP-1) and octamer, all of which contribute to the regulation of IL-2 gene expression. Electrophoretic mobility shift assays showed that TGF-beta1 markedly increased NF-AT, NF-kappaB and AP-1 binding to their respective cognate DNA binding sites, whereas octamer binding remained constant, as compared with untreated cells. Employing a reporter gene expression system with p(NF-kappaB)3-CAT, p(NF-AT)3-CAT and p(AP-1)3-CAT, TGF-beta1 treatment of transfected EL4 cells induced a dose-related increase in chloramphenicol acetyltransferase activity that correlated well with the DNA binding profile found in the electrophoretic mobility shift assay studies. These results show that TGF-beta1, in the absence of any additional stimuli, up-regulates the activity of key transcription factors involved in IL-2 gene expression, including NF-AT, NF-kappaB and AP-1, to help promote IL-2 mRNA expression by EL4 cells.

Tungsten trioxide as high-{kappa} gate dielectric for highly transparent and temperature-stable zinc-oxide-based thin-film transistors

Energy Technology Data Exchange (ETDEWEB)

Lorenz, Michael; Wenckstern, Holger von; Grundmann, Marius [Universitaet Leipzig, Fakultaet fuer Physik und Geowissenschaften, Institut fuer Experimentelle Physik II, Linnestr. 5, 04103 Leipzig (Germany)

2012-07-01

We demonstrate metal-insulator-semiconductor field-effect transistors with high-{kappa}, room-temperature deposited, highly transparent tungsten trioxide (WO{sub 3}) as gate dielectric. The channel material consists of a zinc oxide (ZnO) thin-film. The transmittance and resistivity of WO{sub 3} films was tuned in order to obtain a highly transparent and insulating WO{sub 3} dielectric. The devices were processed by standard photolithography using lift-off technique. On top of the WO{sub 3} dielectric a highly transparent and conductive oxide consisting of ZnO: Al 3% wt. was deposited. The gate structure of the devices exhibits an average transmittance in the visible spectral range of 86%. The on/off-current ratio is larger than 10{sup 8} with off- and gate leakage-currents below 3 x 10{sup -8} A/cm{sup 2}. Due to the high relative permittivity of {epsilon}{sub r} {approx} 70, a gate voltage sweep of only 2 V is necessary to turn the transistor on and off with a minimum subthreshold swing of 80 mV/decade. The channel mobility of the transistors equals the Hall-effect mobility with a value of 5 cm{sup 2}/Vs. It is furthermore shown, that the devices are stable up to operating temperatures of at least 150 C.

20-Hydroxycholecalciferol, product of vitamin D3 hydroxylation by P450scc, decreases NF-kappaB activity by increasing IkappaB alpha levels in human keratinocytes.

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Zorica Janjetovic

Full Text Available The side chain of vitamin D3 is hydroxylated in a sequential manner by cytochrome P450scc (CYP11A1 to form 20-hydroxycholecalciferol, which can induce growth arrest and differentiation of both primary and immortalized epidermal keratinocytes. Since nuclear factor-kappaB (NF-kappaB plays a pivotal role in the regulation of cell proliferation, differentiation and apoptosis, we examined the capability of 20-hydroxycholecalciferol to modulate the activity of NF-kappaB, using 1,25-dihydroxycholecalciferol (calcitriol as a positive control. 20-hydroxycholecalciferol inhibits the activation of NFkappaB DNA binding activity as well as NF-kappaB-driven reporter gene activity in keratinocytes. Also, 20-hydroxycholecalciferol induced significant increases in the mRNA and protein levels of the NF-kappaB inhibitor protein, IkappaB alpha, in a time dependent manner, while no changes in total NF-kappaB-p65 mRNA or protein levels were observed. Another measure of NF-kappaB activity, p65 translocation from the cytoplasm into the nucleus was also inhibited in extracts of 20-hydroxycholecalciferol treated keratinocytes. Increased IkappaB alpha was concomitantly observed in cytosolic extracts of 20-hydroxycholecalciferol treated keratinocytes, as determined by immunoblotting and immunofluorescent staining. In keratinocytes lacking vitamin D receptor (VDR, 20-hydroxycholecalciferol did not affect IkappaB alpha mRNA levels, indicating that it requires VDR for its action on NF-kappaB activity. Comparison of the effects of calcitrol, hormonally active form of vitamin D3, with 20-hydrocholecalciferol show that both agents have a similar potency in inhibiting NF-kappaB. Since NF-kappaB is a major transcription factor for the induction of inflammatory mediators, our findings indicate that 20-hydroxycholecalciferol may be an effective therapeutic agent for inflammatory and hyperproliferative skin diseases.

A kinetic analysis of kappa-opioid agonist binding using the selective radioligand (/sup 3/H)U69593

Energy Technology Data Exchange (ETDEWEB)

Smith, J.A.; Hunter, J.C.; Hill, R.G.; Hughes, J.

1989-07-01

The interaction of the nonselective opioid ligand (3H)bremazocine and of the kappa-opioid (3H)U69593 with the kappa-receptor was investigated in guinea-pig cortical membranes. Each radioligand bound to a single population of high-affinity sites, although (3H)U69593 apparently recognised only 70% of those sites labelled by (3H)bremazocine. Naloxone and the kappa-selective ligands U69593 and PD117302 exhibited full inhibition of the binding of both radioligands. Kinetic analysis demonstrated biphasic rates of association and dissociation for both (3H)bremazocine and (3H)U69593. Detailed analysis of the binding of (3H)U69593 revealed that the fast rate of association was dependent on radioligand concentration, in contrast to the slow rate, which was independent of ligand concentration. Guanylyl-5'-imidodiphosphate (GppNHp) inhibited binding of (3H)U69593; saturation analysis demonstrated that the inhibitory effects of GppNHp resulted in a decrease in affinity without any significant change in binding capacity. GppNHp attenuated the formation of the slow component of (3H)U69593 binding, while accelerating the fast component. The data are consistent with the formation of a high-affinity complex between the kappa-receptor and a guanine nucleotide binding protein. Guanine nucleotides promote the dissociation of this ternary complex and the stabilisation of a lower-affinity state of the receptor.

A Gordeyev integral for electrostatic waves in a magnetized plasma with a kappa velocity distribution

International Nuclear Information System (INIS)

Mace, R.L.

2003-01-01

A Gordeyev-type integral for the investigation of electrostatic waves in magnetized plasma having a kappa or generalized Lorentzian velocity distribution is derived. The integral readily reduces, in the unmagnetized and parallel propagation limits, to simple expressions involving the Z κ function. For propagation perpendicular to the magnetic field, it is shown that the Gordeyev integral can be written in closed form as a sum of two generalized hypergeometric functions, which permits easy analysis of the dispersion relation for electrostatic waves. Employing the same analytical techniques used for the kappa distribution, it is further shown that the well-known Gordeyev integral for a Maxwellian distribution can be written very concisely as a generalized hypergeometric function in the limit of perpendicular propagation. This expression, in addition to its mathematical conciseness, has other advantages over the traditional sum over modified Bessel functions form. Examples of the utility of these generalized hypergeometric series, especially how they simplify analyses of electrostatic waves propagating perpendicular to the magnetic field, are given. The new expression for the Gordeyev integral for perpendicular propagation is solved numerically to obtain the dispersion relations for the electrostatic Bernstein modes in a plasma with a kappa distribution

Kappa Opioid Receptors Mediate where Fear Is Expressed Following Extinction Training

Science.gov (United States)

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

2011-01-01

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

X-ray inactivation and reactivation characteristics of the phage 'kappa'

International Nuclear Information System (INIS)

Bhattacharyya, S.C.; Samad, S.A.; Mandal, J.C.; Chatterjee, S.N.

1991-01-01

Vibrio cholerae temperate phage 'kappa' was inactivated by X-ray (60 kV) in a dose dependent manner, the inactivation dose leading to 37% survival (D 37 ) in PBS, pH 7.4 being 0.36 kGy. The phages were significantly protected against X-ray irradiation when histidine or cysteine or both were present in PBS or when phages were irradiated in nutrient broth. The maximum protection was offered when histidine (10.0 nM) and cysteine (10.0 nM) were both present in PBS (dose enhancement factor being 4.17). The X-irradiated 'kappa' phages also underwent a small but significant Weigle reactivation and also Weigle mutagenesis in the UV-irradiated V. cholerae host H218Sm r . The Weigle factor (WF) or the frequency of clear plaque mutants increased with increasing UV dose, attained a maximum at the UV dose of 2.4 Jm -2 and thereafter decreased gradually with further increase of UV dose. The X-ray dose (D)-survival (S) curves could be empirically described by the equation S=exp-(aD+bD 2 ) where 'a' and 'b' are constants depending on the irradiation conditions and good agreement between the theoretical curves and experimental data was obtained. (author). 1 5 refs., 2 fig., 1 tab

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

Science.gov (United States)

Shizgal, Bernie D.

2018-05-01

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

NF-kappaB and p53 are the dominant apoptosis-inducing transcription factors elicited by the HIV-1 envelope.

Science.gov (United States)

Perfettini, Jean-Luc; Roumier, Thomas; Castedo, Maria; Larochette, Nathanael; Boya, Patricia; Raynal, Brigitte; Lazar, Vladimir; Ciccosanti, Fabiola; Nardacci, Roberta; Penninger, Josef; Piacentini, Mauro; Kroemer, Guido

2004-03-01

The coculture of cells expressing the HIV-1 envelope glycoprotein complex (Env) with cells expressing CD4 results into cell fusion, deregulated mitosis, and subsequent cell death. Here, we show that NF-kappaB, p53, and AP1 are activated in Env-elicited apoptosis. The nuclear factor kappaB (NF-kappaB) super repressor had an antimitotic and antiapoptotic effect and prevented the Env-elicited phosphorylation of p53 on serine 15 and 46, as well as the activation of AP1. Transfection with dominant-negative p53 abolished apoptosis and AP1 activation. Signs of NF-kappaB and p53 activation were also detected in lymph node biopsies from HIV-1-infected individuals. Microarrays revealed that most (85%) of the transcriptional effects of HIV-1 Env were blocked by the p53 inhibitor pifithrin-alpha. Macroarrays led to the identification of several Env-elicited, p53-dependent proapoptotic transcripts, in particular Puma, a proapoptotic "BH3-only" protein from the Bcl-2 family known to activate Bax/Bak. Down modulation of Puma by antisense oligonucleotides, as well as RNA interference of Bax and Bak, prevented Env-induced apoptosis. HIV-1-infected primary lymphoblasts up-regulated Puma in vitro. Moreover, circulating CD4+ lymphocytes from untreated, HIV-1-infected donors contained enhanced amounts of Puma protein, and these elevated Puma levels dropped upon antiretroviral therapy. Altogether, these data indicate that NF-kappaB and p53 cooperate as the dominant proapoptotic transcription factors participating in HIV-1 infection.

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

DEFF Research Database (Denmark)

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

the observability of the system is briefly discussed and an extended set-valued observer is presented, with some discussion about the effect of the measurements noise on the final solution. This observer estimates bounds in the errors assuming that the exogenous signals are bounded, providing a safe region......The ability of estimating the position of an underwater vehicle from single range measurements is important in applications where one transducer marks an important geographical point, when there is a limitation in the size or cost of the vehicle, or when there is a failure in a system...... 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...

A Smac-mimetic sensitizes prostate cancer cells to TRAIL-induced apoptosis via modulating both IAPs and NF-kappaB

International Nuclear Information System (INIS)

Dai, Yao; Liu, Meilan; Tang, Wenhua; Li, Yongming; Lian, Jiqin; Lawrence, Theodore S; Xu, Liang

2009-01-01

Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising agent for human cancer therapy, prostate cancer still remains resistant to TRAIL. Both X-linked inhibitor of apoptosis (XIAP) and nuclear factor-kappaB function as key negative regulators of TRAIL signaling. In this study, we evaluated the effect of SH122, a small molecule mimetic of the second mitochondria-derived activator of caspases (Smac), on TRAIL-induced apoptosis in prostate cancer cells. The potential of Smac-mimetics to bind XIAP or cIAP-1 was examined by pull-down assay. Cytotoxicity of TRAIL and/or Smac-mimetics was determined by a standard cell growth assay. Silencing of XIAP or cIAP-1 was achieved by transient transfection of short hairpin RNA. Apoptosis was detected by Annexin V-PI staining followed by flow cytometry and by Western Blot analysis of caspases, PARP and Bid. NF-kappaB activation was determined by subcellular fractionation, real time RT-PCR and reporter assay. SH122, but not its inactive analog, binds to XIAP and cIAP-1. SH122 significantly sensitized prostate cancer cells to TRAIL-mediated cell death. Moreover, SH122 enhanced TRAIL-induced apoptosis via both the death receptor and the mitochondrial pathway. Knockdown of both XIAP and cIAP-1 sensitized cellular response to TRAIL. XIAP-knockdown attenuated sensitivity of SH122 to TRAIL-induced cytotoxicity, confirming that XIAP is an important target for IAP-inhibitor-mediated TRAIL sensitization. SH122 also suppressed TRAIL-induced NF-kappaB activation by preventing cytosolic IkappaB-alpha degradation and RelA nuclear translocation, as well as by suppressing NF-kappaB target gene expression. These results demonstrate that SH122 sensitizes human prostate cancer cells to TRAIL-induced apoptosis by mimicking Smac and blocking both IAPs and NF-kappaB. Modulating IAPs may represent a promising approach to overcoming TRAIL-resistance in human prostate cancer with constitutively active NF-kappaB signaling

Optimization of Serum Immunoglobulin Free Light Chain Analysis for Subclassification of Cardiac Amyloidosis.

Science.gov (United States)

Halushka, Marc K; Eng, George; Collins, A Bernard; Judge, Daniel P; Semigran, Marc J; Stone, James R

2015-06-01

Accurate and rapid classification of cardiac amyloidosis is important for patient management. We have optimized the use of serum free light chain kappa and lambda values to differentiate immunoglobulin light chain amyloid (AL) amyloidosis from transthyretin amyloid and amyloid A using 85 cases of tissue-proven cardiac amyloidosis, in which there was direct classification of amyloidosis by mass spectrometry or immunofluorescence. The serum free light chain kappa/lambda ratios were non-overlapping for the three major groups: AL-lambda (0.01-0.41, n = 30), non-AL (0.52-2.7, n = 43), and AL-kappa (6.7-967, n = 12). A kappa/lambda ratio value between 0.5 and 5.0 had 100 % sensitivity and 100 % specificity for distinguishing AL amyloidosis from non-AL amyloidosis. This optimized range for serum light chain kappa/lambda ratio provides extremely robust classification of cardiac amyloidosis. Cases of cardiac amyloidosis in which the serum kappa/lambda free light chain ratio falls close to these new cutoff values may benefit most from direct amyloid subtyping.

Development of inhomogeneous {kappa}-{epsilon}-{upsilon}{sup 2} turbulence model for 3D flow analysis of SMART-P

Energy Technology Data Exchange (ETDEWEB)

Chun, K. H.; Whang, Y. D.; Yoon, H. Y.; Kim, H. C

2003-07-01

The objective of the present report is to select and develop a turbulence model that will be implemented in TASS-3D code for 3-D heat and fluid analysis on the integral reactor, SMART-P primary coolant system. The turbulence model was selected with the consideration on the economy, accuracy, theorization and applicability for the complex three dimensional flow, natural convection and the high Reynolds number turbulent flow of SMART-P.On the models investigated in this present study, the standard {kappa}-{epsilon} model of high Reynolds model, the {kappa}-{epsilon}-{upsilon}{sup 2} model and ERRSM of low Reynolds model were selected out of them finally. The {kappa}-{epsilon}-{upsilon}{sup 2} model was selected as the applicable turbulence model for three dimensional flow analysis of SMART-P. The problem of original {kappa}-{epsilon}-{upsilon}{sup 2} model is the amplification of the pressure strain rate in the log region. The amplification is caused by Elliptic Relaxation Equation(ERE). The present model approaches inhomogeneous for the source term of the ERE to reduce the pressure-strain amplification. The source term was decomposed into homogeneous part and inhomogeneous part and derived as a form of variable coefficients of the ERE. The pressure strain and dissipation terms were fully coupled with the source term of the ERE. The pressure diffusion was modified to treat the boundary conditions indirectly and the pressure strain of the inhomogeneous correction ERE was noticeably decreased in both log layer and outer layer. The results of the inhomogeneous correction {kappa}-{epsilon}-{upsilon}{sup 2} model showed a good agreement with DNS results for channel flows and estimated improved results on the turbulent components in comparison with other models.

Characterization of kappa opioid binding using dynorphin A1-13 and U69,593 in the rat brain

Energy Technology Data Exchange (ETDEWEB)

Devlin, T.; Shoemaker, W.J. (Univ. of Connecticut Health Center, Farmington (USA))

1990-05-01

Previous studies of kappa opioid binding sites have suggested heterogeneous binding to this class of opioid receptors. To further investigate kappa receptor heterogeneity, we analyzed the binding properties of various kappa-selective ligands in rat brain homogenates. Displacement assays were carried out using (3H)bremazocine in the presence of various displacing ligands under mu and delta receptor-blocked conditions. Homologous displacement of (3H)bremazocine produced shallow displacement which best fit a two-site model of drug-receptor interaction. Dynorphin A1-13 and U69,593 exhibited similar biphasic displacement of (3H)bremazocine. Maximal displacement by these ligands, however, represented only approximately 55% of total (3H)bremazocine binding, which suggests the existence of a third component of (3H)bremazocine binding. Biphasic displacement by dynorphin A1-13 was detected in tissue throughout the brain and the spinal cord, whereas the dynorphin-resistant component of (3H)bremazocine binding was uniquely absent in the spinal cord. U50,488H, tifluadom and ethylketocyclazocine appeared to displace from additional, dynorphin-insensitive sites, as their maximal displacement exceeded that seen with either dynorphin A1-13 or U69,593. These results strongly suggest the existence of at least three components of non-mu, non-delta (3H)bremazocine binding in the rat brain: two with differential affinity for dynorphin A1-13 and U69-593 (kappa-1 and kappa-2 sites), and a third (termed here R1) that was further resolved into two binding sites by bremazocine. Preliminary analysis of the R1 component using naloxone revealed one high-affinity site, which may be opiate in nature, and a second site whose binding properties closely resemble those of the sigma receptor described by others.

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

DEFF Research Database (Denmark)

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

2006-01-01

mononuclear cells (MNC). To elucidate the mechanism behind SPIR's apoptotic effect, we investigated the relation between apoptosis and cytokine suppression for SPIR along with the apoptosis-inducing and antiinflammatory drug sulfasalazine (SFZ). Using human MNC, we found that SPIR and SFZ, at concentrations...... 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......-kappaB, 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...

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

Science.gov (United States)

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

2002-01-01

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

Inhibitory effects of curcumin and capsaicin on phorbol ester-induced activation of eukaryotic transcription factors, NF-kappaB and AP-1.

Science.gov (United States)

Surh, Y J; Han, S S; Keum, Y S; Seo, H J; Lee, S S

2000-01-01

Recently, considerable attention has been focused on identifying dietary and medicinal phytochemicals that can inhibit, retard or reverse the multi-stage carcinogenesis. Spices and herbs contain phenolic substances with potent antioxidative and chemopreventive properties. Curcumin, a yellow colouring agent from turmeric and capsaicin, a pungent principle of red pepper exhibit profound anticarcinogenic and antimutagenic activities. Two well-defined eukaryotic transcription factors, nuclear factor-kappa B (NF-kappaB) and activator protein 1 (AP-1) have been implicated in pathogenesis of many human diseases including cancer. These transcription factors are known to be activated by a wide array of external stimuli, such as tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), tumor necrosis factor, reactive oxygen species, bacterial lipopolysaccharide, and ultraviolet. In the present study, we found that topical application of TPA onto dorsal skin of female ICR mice resulted in marked activation of epidermal NF-kappaB and AP-1. Curcumin and capsaicin, when topically applied prior to TPA, significantly attenuated TPA-induced activation of each transcription factor in mouse skin. Likewise, both compounds inhibited NF-kappaB and AP-1 activation in cultured human promyelocytic leukemia (HL-60) cells stimulated with TPA. Based on these findings, it is likely that curcumin and capsaicin exert anti-tumor promotional effects through suppression of the tumor promoter-induced activation of transcription factors, NF-kappaB and AP-1.

Bypass of a psoralen DNA interstrand cross-link by DNA polymerases beta, iota, and kappa in vitro

Science.gov (United States)

Smith, Leigh A.; Makarova, Alena V.; Samson, Laura; Thiesen, Katherine E.; Dhar, Alok; Bessho, Tadayoshi

2012-01-01

Repair of DNA inter-strand cross-links in mammalian cells involves several biochemically distinctive processes, including the release of one of the cross-linked strands and translesion DNA synthesis (TLS). In this report, we investigated in vitro TLS activity of psoralen DNA inter-strand cross-link by three DNA repair polymerases, DNA polymerase beta, kappa and iota. DNA polymerase beta is capable of bypassing a psoralen cross-link with a low efficiency. Cell extracts prepared from DNA polymerase beta knockout mouse embryonic fibroblast showed a reduced bypass activity of the psoralen cross-link and purified DNA polymerase beta restored the bypass activity. In addition, DNA polymerase iota mis-incorporated thymine across the psoralen cross-link and DNA polymerase kappa extended these mis-paired primer ends, suggesting that DNA polymerase iota may serve as an inserter and DNA polymerase kappa may play a role as an extender in the repair of psoralen DNA inter-strand cross-links. The results demonstrated here indicate that multiple DNA polymerases could participate in TLS steps in mammalian DNA inter-strand cross-link repair. PMID:23106263

Synthesis of superabsorbent hydrogel by radiation crosslinking of acrylic acid, semi-refined kappa-carrageenan and sugarcane bagasse blend

International Nuclear Information System (INIS)

Jizmundo, Leonie-Lou Dominguez

2015-04-01

Superabsorbent hydrogels have three-dimensional networks that enable it to exhibit great water absorption capacity leading to its promising applications. However, existing commercial hydrogels are mainly acrylic acid which causes environmental problems. In this study, the incorporation of agricultural waste as filler and polysaccharide from natural sources as binder for the production of superabsorbent hydrogel was done to reduce the use of acrylic acid as well as its environmental impact while adding value to the incorporated materials. A series of superabsorbent hydrogel with the blend of acrylic acid, semi-refined kappa carrageenan and sugarcane bagasse were synthesized by radiation crosslinking. The gel fraction and swelling capacity of the hydrogels were determined and studied. The characterizations were facilitated by Fourier transform infrared spectroscopy technique (FTIR) and Thermogravimetric Analysis (TGA). In the results obtained from analyses, the characteristic peaks of acrylic acid and sugarcane bagasse were observed in the FTIR spectra and the three step peaks if synthesized hydrogel in its TGA implies an improvement in thermal stability of the product. The synthesized superabsorbent hydrogel blends had exhibited comparable gel fraction to that of the polyacrylic acid hydrogel, had great swelling capacity, and achieved equilibrium degree of swelling within 72-96 hours. The optimum synthesized superabsorbent hydrogel is 3% semi-refined kappa-carrageenan, 3% sugarcane bagasse, 15% acrylic acid neutralize up to 50% and irradiated at 15kGy dose which exhibited a swelling of 599.53 and gel fraction of 39.73. (author)

Oligo-carrageenan kappa increases NADPH, ascorbate and glutathione syntheses and TRR/TRX activities enhancing photosynthesis, basal metabolism, and growth in Eucalyptus trees.

Science.gov (United States)

González, Alberto; Moenne, Fabiola; Gómez, Melissa; Sáez, Claudio A; Contreras, Rodrigo A; Moenne, Alejandra

2014-01-01

In order to analyze the effect of OC kappa in redox status, photosynthesis, basal metabolism and growth in Eucalyptus globulus, trees were treated with water (control), with OC kappa at 1 mg mL(-1), or treated with inhibitors of NAD(P)H, ascorbate (ASC), and glutathione (GSH) syntheses and thioredoxin reductase (TRR) activity, CHS-828, lycorine, buthionine sulfoximine (BSO), and auranofin, respectively, and with OC kappa, and cultivated for 4 months. Treatment with OC kappa induced an increase in NADPH, ASC, and GSH syntheses, TRR and thioredoxin (TRX) activities, photosynthesis, growth and activities of basal metabolism enzymes such as rubisco, glutamine synthetase (GlnS), adenosine 5'-phosphosulfate reductase (APR), involved in C, N, and S assimilation, respectively, Krebs cycle and purine/pyrimidine synthesis enzymes. Treatment with inhibitors and OC kappa showed that increases in ASC, GSH, and TRR/TRX enhanced NADPH synthesis, increases in NADPH and TRR/TRX enhanced ASC and GSH syntheses, and only the increase in NADPH enhanced TRR/TRX activities. In addition, the increase in NADPH, ASC, GSH, and TRR/TRX enhanced photosynthesis and growth. Moreover, the increase in NADPH, ASC and TRR/TRX enhanced activities of rubisco, Krebs cycle, and purine/pyrimidine synthesis enzymes, the increase in GSH, NADPH, and TRR/TRX enhanced APR activity, and the increase in NADPH and TRR/TRX enhanced GlnS activity. Thus, OC kappa increases NADPH, ASC, and GSH syntheses leading to a more reducing redox status, the increase in NADPH, ASC, GSH syntheses, and TRR/TRX activities are cross-talking events leading to activation of photosynthesis, basal metabolism, and growth in Eucalyptus trees.

Oligo-carrageenan kappa increases NADPH, ascorbate and glutathione syntheses and TRR/TRX activities enhancing photosynthesis, basal metabolism, and growth in Eucalyptus trees

Directory of Open Access Journals (Sweden)

Alberto eGonzález

2014-10-01

Full Text Available In order to analyze the effect of OC kappa in redox status, photosynthesis, basal metabolism and growth in Eucalyptus globulus, trees were treated with water (control, with OC kappa at 1 mg mL-1, or treated with inhibitors of NAD(PH, ascorbate (ASC and glutathione (GSH syntheses and thioredoxin reductase (TRR activity, CHS-828, lycorine, buthionine sulfoximine (BSO and auranofin, respectively, and with OC kappa, and cultivated for 4 months. Treatment with OC kappa induced an increase in NADPH, ASC, and GSH syntheses, TRR and thioredoxin (TRX activities, photosynthesis, growth and activities of basal metabolism enzymes such as rubisco, glutamine synthetase (GlnS, adenosine 5´-phosphosulfate reductase (APR, involved in C, N and S assimilation, respectively, Krebs cycle and purine/pyrimidine synthesis enzymes. Treatment with inhibitors and OC kappa showed that increases in ASC, GSH and TRR/TRX enhanced NADPH synthesis, increases in NADPH and TRR/TRX enhanced ASC and GSH syntheses, and only the increase in NADPH enhanced TRR/TRX activities. In addition, the increase in NADPH, ASC, GSH and TRR/TRX enhanced photosynthesis and growth. Moreover, the increase in NADPH, ASC and TRR/TRX enhanced activities of rubisco, Krebs cycle and purine/pyrimidine synthesis enzymes, the increase in GSH, NADPH, and TRR/TRX enhanced APR activity, and the increase in NADPH and TRR/TRX enhanced GlnS activity. Thus, OC kappa increases NADPH, ASC and GSH syntheses leading to a more reducing redox status, the increase in NADPH, ASC, GSH syntheses and TRR/TRX activities are cross-talking events leading to activation of photosynthesis, basal metabolism and growth in Eucalyptus trees.

Transcriptional down-regulation of thromboxane A(2) receptor expression via activation of MAPK ERK1/2, p38/NF-kappaB pathways

DEFF Research Database (Denmark)

Zhang, Wei; Zhang, Yaping; Edvinsson, Lars

2009-01-01

culture of the arteries, VSMC TP receptors were studied by using myography, real-time PCR and immunohistochemistry. We observed that organ culture for 24 and 48 h resulted in depressed TP receptor-mediated contraction in the VSMC, in parallel with decreased TP receptor mRNA and protein expressions....... Phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2), p38 and nuclear factor-kappaB (NF-kappaB) was seen by Western blot within 1-3 h after organ culture. Inhibition of ERK1/2, p38 or NF-kappaB reversed depressed contraction as well as decreased receptor mRNA expression. Actinomycin D...

Transcriptional Down-Regulation of Thromboxane A(2) Receptor Expression via Activation of MAPK ERK1/2, p38/NF-kappaB Pathways

DEFF Research Database (Denmark)

Zhang, Wei; Zhang, Yaping; Edvinsson, Lars

2008-01-01

culture of the arteries, VSMC TP receptors were studied by using myography, real-time PCR and immunohistochemistry. We observed that organ culture for 24 and 48 h resulted in depressed TP receptor-mediated contraction in the VSMC, in parallel with decreased TP receptor mRNA and protein expressions....... Phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2), p38 and nuclear factor-kappaB (NF-kappaB) was seen by Western blot within 1-3 h after organ culture. Inhibition of ERK1/2, p38 or NF-kappaB reversed depressed contraction as well as decreased receptor mRNA expression. Actinomycin D...

Diagnostic Value of Senior Dental Students in Yazd About of Detection the Proximal Caries on Panoramic Radiographs Compared to Detection of Experts in 1394

Directory of Open Access Journals (Sweden)

E Romoozi

2016-08-01

Full Text Available Introduction: Tooth decay is the most common chronic disease of man in the world and dentists should receive the capability to accurately diagnose of tooth decay during the training courses. In addition to clinical examination, the panoramic view and intraoral radiography is usually used for the caries detection. Therefore, the detection of caries on X-ray images can have a role in treatment planning. Methods: In this analytical study, 10 panoramic radiographies that randomly selected, separately given to 30 senior dental students and 2 professors (in order to determine the gold standard. Data were analyzed using SPSS 17 software, diagnostic tables and indexes were prepared and the results were analyzed by Kappa test. Moreover, in order to determine the agreement between the professors and students about the depth of the decay the weighted kappa coefficient was used. Results: The kappa value about detection of presence or absence of proximal caries between professors and students's diagnosis was 0.428 (P value=0.001. Diagnostic sensitivity, specificity, positive predictive value and negative predictive value obtained by students in caries detection were %47, %91.9, %63 and %85.3, respectively. Coefficient of agreement in detection of depth diagnosis obtained by professors and students was 0.361(p value=0.000. Conclusion: The diagnostic capability of senior dental students about caries detection was fair and depth diagnosis was slight.

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

Energy Technology Data Exchange (ETDEWEB)

Nicholls, David C.; Dopita, Michael A.; Sutherland, Ralph S.; Kewley, Lisa J. [Research School of Astronomy and Astrophysics, Australian National University, Cotter Rd., Weston ACT 2611 (Australia); Palay, Ethan, E-mail: david@mso.anu.edu.au [Department of Astronomy, Ohio State University, Columbus, OH 43210 (United States)

2013-08-15

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

Neuroanatomical patterns of the mu, delta, and kappa opioid receptors of rat brain as determined by quantitative in vitro autoradiography

International Nuclear Information System (INIS)

Tempel, A.; Zukin, R.S.

1987-01-01

Highly specific radioligands and quantitative autoradiography reveal strikingly different neuroanatomical patterns for the mu, delta, and kappa opioid receptors of rat brain. The mu receptors are most densely localized in patches in the striatum, layers I and III of the cortex, the pyramidal cell layer of the hippocampal formation, specific nuclei of the thalamus, the pars reticulata of the substantia nigra, the interpeduncular nucleus, and the locus coeruleus. In contrast, delta receptors are highly confined, exhibiting selective localization in layers I, II, and VIa of the neocortex, a diffuse pattern in the striatum, and moderate concentration in the pars reticulata of the substantia nigra and in the interpeduncular nucleus. delta receptors are absent in most other brain structures. This distribution is unexpected in that the enkephalins, the putative endogenous ligands of the delta receptor, occur essentially throughout the brain. The kappa receptors of rat brain exhibit a third pattern distinct from that of the mu and delta receptors. kappa receptors occur at low density in patches in the striatum and at particularly high density in the nucleus accumbens, along the pyramidal and molecular layers of the hippocampus, in the granular cell layer of the dentate gyrus, specific midline nuclei of the thalamus, and hindbrain regions. kappa receptors appear to be uniformly distributed across regions in the neocortex with the exception of layer III, which revealed only trace levels of binding. An important conclusion of the present study is that delta receptors occur at high density only in the forebrain and in two midbrain structures, whereas mu and kappa receptors exhibit discrete patterns in most major brain regions

NF-kappa B activity in T cells stably expressing the Tax protein of human T cell lymphotropic virus type I

International Nuclear Information System (INIS)

Lacoste, J.; Cohen, L.; Hiscott, J.

1991-01-01

The effect of constitutive Tax expression on the interaction of NF-κ B with its recognition sequence and on NF-κ B-dependent gene expression was examined in T lymphoid Jurkat cell lines (19D and 9J) stably transformed with a Tax expression vector. Tax expressing T cell lines contained a constitutive level of NF-κ B binding activity, detectable by mobility shift assay and uv cross-linking using a palindromic NF-κ B probe homologous to the interferon beta PRDII site. In Jurkat and NC2.10 induction with phorbol esters resulted in the appearance of new DNA binding proteins of 85, 75, and 54 kDa, whereas in Tax expressing cells the 85-kDa protein and a 92-kDa DNA binding protein were constitutively induced. Expression of Tax protein in 19D and 9J resulted in transcription of the endogenous NF-kappa B-dependent granulocyte-macrophage colony stimulating factor gene and increased basal level expression of transfected NF-kappa B-regulated promoters. Nonetheless transcription of both the endogenous and the transfected gene was inducible by PMA treatment. Tax expression in Jurkat T cells may alter the stoichiometry of NF-kappa B DNA binding proteins and thus change the expression of NF-kappa B-regulated promoters

DMPD: Convergence of the NF-kappaB and IRF pathways in the regulation of the innateantiviral response. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 17706453 Convergence of the NF-kappaB and IRF pathways in the regulation of the innatea... (.png) (.svg) (.html) (.csml) Show Convergence of the NF-kappaB and IRF pathways in the regulation of the innatea... IRF pathways in the regulation of the innateantiviral response. Authors Hiscott J. Publication Cytokine Gro

NIK is involved in constitutive activation of the alternative NF-{kappa}B pathway and proliferation of pancreatic cancer cells

Energy Technology Data Exchange (ETDEWEB)

Nishina, Takashi [Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Yamaguchi, Noritaka [Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, 513 Wasedatsurumaki-cho, Shinjuku-ku, Tokyo 162-0041 (Japan); Gohda, Jin [Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Semba, Kentaro [Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, 513 Wasedatsurumaki-cho, Shinjuku-ku, Tokyo 162-0041 (Japan); Department of Life Science and Medical Bio-science, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480 (Japan); Inoue, Jun-ichiro, E-mail: jun-i@ims.u-tokyo.ac.jp [Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan)

2009-10-09

Pancreatic cancer has one of the poorest prognoses among human neoplasms. Constitutive activation of NF-{kappa}B is frequently observed in pancreatic cancer cells and is involved in their malignancy. However, little is known about the molecular mechanism of this constitutive NF-{kappa}B activation. Here, we show that the alternative pathway is constitutively activated and NF-{kappa}B-inducing kinase (NIK), a mediator of the alternative pathway, is significantly expressed in pancreatic cancer cells. siRNA-mediated silencing of NIK expression followed by subcellular fractionation revealed that NIK is constitutively involved in the processing of p100 and nuclear transport of p52 and RelB in pancreatic cancer cells. In addition, NIK silencing significantly suppressed proliferation of pancreatic cancer cells. These results clearly indicate that NIK is involved in the constitutive activation of the alternative pathway and controls cell proliferation in pancreatic cancer cells. Therefore, NIK might be a novel target for the treatment of pancreatic cancer.

Out-of-range INR values and outcomes among new warfarin patients with non-valvular atrial fibrillation.

Science.gov (United States)

Nelson, Winnie W; Wang, Li; Baser, Onur; Damaraju, Chandrasekharrao V; Schein, Jeffrey R

2015-02-01

Although efficacious in stroke prevention in non-valvular atrial fibrillation, many warfarin patients are sub-optimally managed. To evaluate the association of international normalized ratio control and clinical outcomes among new warfarin patients with non-valvular atrial fibrillation. Adult non-valvular atrial fibrillation patients (≥18 years) initiating warfarin treatment were selected from the US Veterans Health Administration dataset between 10/2007 and 9/2012. Valid international normalized ratio values were examined from the warfarin initiation date through the earlier of the first clinical outcome, end of warfarin exposure or death. Each patient contributed multiple in-range and out-of-range time periods. The relative risk ratios of clinical outcomes associated with international normalized ratio control were estimated. 34,346 patients were included for analysis. During the warfarin exposure period, the incidence of events per 100 person-years was highest when patients had international normalized ratio 3, patients had significantly increased risk of major bleeding (relative risk ratio: 1.5; 95 % confidence interval 1.2-2.0). In a Veterans Health Administration non-valvular atrial fibrillation population, exposure to out-of-range international normalized ratio values was associated with significantly increased risk of adverse clinical outcomes.

Uncaria rhynchophylla and Rhynchophylline inhibit c-Jun N-terminal kinase phosphorylation and nuclear factor-kappaB activity in kainic acid-treated rats.

Science.gov (United States)

Hsieh, Ching-Liang; Ho, Tin-Yun; Su, Shan-Yu; Lo, Wan-Yu; Liu, Chung-Hsiang; Tang, Nou-Ying

2009-01-01

Our previous studies have shown that Uncaria rhynchophylla (UR) can reduce epileptic seizures. We hypothesized that UR and its major component rhynchophylline (RH), reduce epileptic seizures in rats treated with kainic acid (KA) by inhibiting nuclear factor-kappaB (NF-kappaB) and activator-protein-1 (AP-1) activity, and by eliminating superoxide anions. Therefore, the level of superoxide anions and the DNA binding activities of NF-kappaB and AP-1 were measured. Sprague-Dawley (SD) rats were pre-treated with UR (1.0 g/kg, i.p.), RH (0.25 mg/kg, i.p.), or valproic acid (VA, 250 mg/kg, i.p.) for 3 days and then KA was administered intra-peritoneal (i.p.). The results indicated that UR, RH, and VA can reduce epileptic seizures and the level of superoxide anions in the blood. Furthermore, KA was demonstrated to induce the DNA binding activities of NF-kappaB and AP-1. However, these inductions were inhibited by pre-treatment with UR, RH, or VA for 3 days. Moreover, UR and RH were shown to be involved in the suppression of c-Jun N-terminal kinase (JNK) phosphorylation. This study suggested that UR and RH have antiepileptic effects in KA-induced seizures and are associated with the regulation of the innate immune system via a reduction in the level of superoxide anions, JNK phosphorylation, and NF-kappaB activation.

Interreader agreement in the assessment of magnetic resonance images of rheumatoid arthritis wrist and finger joints--an international multicenter study

DEFF Research Database (Denmark)

Østergaard, Mikkel; Klarlund, Mette; Lassere, M

2001-01-01

and iv Gd (Techniques A and C), these rates were 86% (synovitis) and 97% (bone lesions). Corresponding intraclass correlation coefficients (quadratic weighted kappas) were 0.44-0.68, mean 0.58 (synovitis), and 0.44-0.69, mean 0.62 (bone lesion), i.e., in the moderate to good range. Unweighted kappa...... values were in the low to moderate range, generally lowest for JSN (... in assessing synovitis and bone destruction in RA multicenter studies....

(/sup 3/H)diprenorphine binding to kappa-sites in guinea-pig and rat brain: Evidence for apparent heterogeneity

Energy Technology Data Exchange (ETDEWEB)

Wood, M.S.; Traynor, J.R.

1989-07-01

The binding of the unselective opioid antagonist (/sup 3/H)diprenorphine to homogenates prepared from rat brain and from guinea-pig brain and cerebellum has been studied in HEPES buffer containing 10 mM Mg2+ ions. Sequential displacement of bound (/sup 3/H)diprenorphine by ligands with selectivity for mu-, delta-, and kappa-opioid receptors uncovers the multiple components of binding. In the presence of cold ligands that occupy all mu-, delta-, and kappa-sites, opioid binding still remains. This binding represents 20% of total specific sites and is displaced by naloxone. The nature of these undefined opioid binding sites is discussed.

Oligo-carrageenan kappa-induced reducing redox status and increase in TRR/TRX activities promote activation and reprogramming of terpenoid metabolism in Eucalyptus trees.

Science.gov (United States)

González, Alberto; Gutiérrez-Cutiño, Marlen; Moenne, Alejandra

2014-06-05

In order to analyze whether the reducing redox status and activation of thioredoxin reductase (TRR)/thioredoxin(TRX) system induced by oligo-carrageenan (OC) kappa in Eucalyptus globulus activate secondary metabolism increasing terpenoid synthesis, trees were sprayed on the leaves with water, with OC kappa, or with inhibitors of NAD(P)H, ascorbate (ASC) and (GSH) synthesis and TRR activity, CHS-828, lycorine, buthionine sulfoximine (BSO) and auranofine, respectively, and with OC kappa and cultivated for four months. The main terpenoids in control Eucalyptus trees were eucalyptol (76%), α-pinene (7.4%), aromadendrene (3.6%), silvestrene (2.8%), sabinene (2%) and α-terpineol (0.9%). Treated trees showed a 22% increase in total essential oils as well as a decrease in eucalyptol (65%) and sabinene (0.8%) and an increase in aromadendrene (5%), silvestrene (7.8%) and other ten terpenoids. In addition, treated Eucalyptus showed seven de novo synthesized terpenoids corresponding to carene, α-terpinene, α-fenchene, γ-maaliene, spathulenol and α-camphenolic aldehyde. Most increased and de novo synthesized terpenoids have potential insecticidal and antimicrobial activities. Trees treated with CHS-828, lycorine, BSO and auranofine and with OC kappa showed an inhibition of increased and de novo synthesized terpenoids. Thus, OC kappa-induced reducing redox status and activation of TRR/TRX system enhance secondary metabolism increasing the synthesis of terpenoids and reprogramming of terpenoid metabolism in Eucalyptus trees.

Oligo-Carrageenan Kappa-Induced Reducing Redox Status and Increase in TRR/TRX Activities Promote Activation and Reprogramming of Terpenoid Metabolism in Eucalyptus Trees

Directory of Open Access Journals (Sweden)

Alberto González

2014-06-01

Full Text Available In order to analyze whether the reducing redox status and activation of thioredoxin reductase (TRR/thioredoxin(TRX system induced by oligo-carrageenan (OC kappa in Eucalyptus globulus activate secondary metabolism increasing terpenoid synthesis, trees were sprayed on the leaves with water, with OC kappa, or with inhibitors of NAD(PH, ascorbate (ASC and (GSH synthesis and TRR activity, CHS-828, lycorine, buthionine sulfoximine (BSO and auranofine, respectively, and with OC kappa and cultivated for four months. The main terpenoids in control Eucalyptus trees were eucalyptol (76%, α-pinene (7.4%, aromadendrene (3.6%, silvestrene (2.8%, sabinene (2% and α-terpineol (0.9%. Treated trees showed a 22% increase in total essential oils as well as a decrease in eucalyptol (65% and sabinene (0.8% and an increase in aromadendrene (5%, silvestrene (7.8% and other ten terpenoids. In addition, treated Eucalyptus showed seven de novo synthesized terpenoids corresponding to carene, α-terpinene, α-fenchene, γ-maaliene, spathulenol and α-camphenolic aldehyde. Most increased and de novo synthesized terpenoids have potential insecticidal and antimicrobial activities. Trees treated with CHS-828, lycorine, BSO and auranofine and with OC kappa showed an inhibition of increased and de novo synthesized terpenoids. Thus, OC kappa-induced reducing redox status and activation of TRR/TRX system enhance secondary metabolism increasing the synthesis of terpenoids and reprogramming of terpenoid metabolism in Eucalyptus trees.

Inhibition of transcription factor NF-kappaB signaling proteins IKKbeta and p65 through specific cysteine residues by epoxyquinone A monomer: correlation with its anti-cancer cell growth activity.

Science.gov (United States)

Liang, Mei-Chih; Bardhan, Sujata; Pace, Emily A; Rosman, Diana; Beutler, John A; Porco, John A; Gilmore, Thomas D

2006-02-28

Transcription factor NF-kappaB is constitutively active in many human chronic inflammatory diseases and cancers. Epoxyquinone A monomer (EqM), a synthetic derivative of the natural product epoxyquinol A, has previously been shown to be a potent inhibitor of tumor necrosis factor-alpha (TNF-alpha)-induced activation of NF-kappaB, but the mechanism by which EqM inhibits NF-kappaB activation was not known. In this report, we show that EqM blocks activation of NF-kappaB by inhibiting two molecular targets: IkappaB kinase IKKbeta and NF-kappaB subunit p65. EqM inhibits TNF-alpha-induced IkappaBalpha phosphorylation and degradation by targeting IKKbeta, and an alanine substitution for Cys179 in the activation loop of IKKbeta makes it resistant to EqM-mediated inhibition. EqM also directly inhibits DNA binding by p65, but not p50; moreover, replacement of Cys38 in p65 with Ser abolishes EqM-mediated inhibition of DNA binding. Pretreatment of cells with reducing agent dithiothreitol dose-dependently reduces EqM-mediated inhibition of NF-kappaB, further suggesting that EqM directly modifies the thiol group of Cys residues in protein targets. Modifications of the exocyclic alkene of EqM substantially reduce EqM's ability to inhibit NF-kappaB activation. In the human SUDHL-4 lymphoma cell line, EqM inhibits both proliferation and NF-kappaB DNA binding, and activates caspase-3 activity. EqM also effectively inhibits the growth of human leukemia, kidney, and colon cancer cell lines in the NCI's tumor cell panel. Among six colon cancer cell lines, those with low amounts of constitutive NF-kappaB DNA-binding activity are generally more sensitive to growth inhibition by EqM. Taken together, these results suggest that EqM inhibits growth and induces cell death in tumor cells through a mechanism that involves inhibition of NF-kappaB activity at multiple steps in the signaling pathway.

Emotion rendering in music: range and characteristic values of seven musical variables.

Science.gov (United States)

Bresin, Roberto; Friberg, Anders

2011-10-01

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

Rapid analysis of rearranged kappa light chain genes of circulating polysaccharide-specific B lymphocytes by means of immunomagnetic beads and the polymerase chain reaction

DEFF Research Database (Denmark)

Hougs, L; Barington, T; Madsen, HO

1993-01-01

reaction (PCR) using in addition a degenerate kappa light chain signal peptide region primer. The PCR product was cloned into the M13mp18 phage. The cloning efficiency was 100-600 clones/ml of blood. Of the 86 clones sequenced, 90% represented rearranged kappa light chain genes from different antibody...... of the B lymphocytes activated in vivo. Here, we present a method for rapid analysis of the rearranged kappa light chain genes used by human circulating antigen-specific B lymphocytes. After vaccination with Haemophilus influenzae type b capsular polysaccharide (HibCP) conjugated with protein, the Hib...

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

Science.gov (United States)

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

2012-03-01

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.

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

Energy Technology Data Exchange (ETDEWEB)

Wang, Zhiquan; Xue, Liqiong; Guo, Cuicui; Han, Bing; Pan, Chunming; Zhao, Shuangxia; Song, Huaidong [State Key Laboratory of Medical Genomics, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025 (China); Ma, Qinyun, E-mail: qinyunma@126.com [State Key Laboratory of Medical Genomics, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025 (China)

2012-01-27

Highlights: Black-Right-Pointing-Pointer Stevioside ameliorates high-fat diet-induced insulin resistance. Black-Right-Pointing-Pointer Stevioside alleviates the adipose tissue inflammation. Black-Right-Pointing-Pointer Stevioside reduces macrophages infiltration into the adipose tissue. Black-Right-Pointing-Pointer Stevioside suppresses the activation of NF-{kappa}B in the adipose tissue. -- Abstract: Accumulating evidence suggests that adipose tissue is the main source of pro-inflammatory molecules that predispose individuals to insulin resistance. Stevioside (SVS) is a widely used sweetener with multiple beneficial effects for diabetic patients. In this study, we investigated the effect of SVS on insulin resistance and the pro-inflammatory state of adipose tissue in mice fed with a high-fat diet (HFD). Oral administration of SVS for 1 month had no effect on body weight, but it significantly improved fasting glucose, basal insulin levels, glucose tolerance and whole body insulin sensitivity. Interestingly, these changes were accompanied with decreased expression levels of several inflammatory cytokines in adipose tissue, including TNF-{alpha}, IL6, IL10, IL1{beta}, KC, MIP-1{alpha}, CD11b and CD14. Moreover, macrophage infiltration in adipose tissue was remarkably reduced by SVS. Finally, SVS significantly suppressed the nuclear factor-kappa b (NF-{kappa}B) signaling pathway in adipose tissue. Collectively, these results suggested that SVS may ameliorate insulin resistance in HFD-fed mice by attenuating adipose tissue inflammation and inhibiting the NF-{kappa}B pathway.

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

2014-12-01

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.

Deuterium values from volcanic glass: A paleoelevation proxy for Oregon's Cascade Range

Science.gov (United States)

Carlson, T. B.; Bershaw, J. T.

2016-12-01

Hydrated volcanic glass has been used as a proxy to constrain Cenozoic paleoclimate across many of the world's mountain ranges. However, there are concerns that volcanic glass may not preserve the isotopic composition of syndepositional meteoric water. The Cascades are an excellent location to study the validity of hydrated volcanic glass as a paleoenvironmental proxy for several reasons. Moisture is derived from a single oceanic source and falls as orographic precipitation in the Cascades, leading to a characteristic altitude effect, or inverse relationship between elevation and the isotopic composition of meteoric water (δD). In addition, past studies have inferred uplift of the Cascades and an increase in the rain shadow effect since the Eocene through independent methods such as changing fossil assemblages, and other isotopic proxies including carbonates and fossil teeth. In this study, δD values of two hydrated tuff samples are compared: one prior to ( 29 Ma) and one following ( 5 Ma) the onset of High Cascade volcanism. The isotopic composition of these samples are interpreted in the context of modern water across the range to understand the potential of volcanic glass as a proxy for paleoelevation in the Pacific Northwest.

Characterisation of Prosopis juliflora seed gum and the effect of its addition to {kappa}-carrageenan systems

Energy Technology Data Exchange (ETDEWEB)

Azero, Edwin G. [Universidade Federal do Estado do Rio de Janeiro (UNIRIO), Rio de Janeiro, RJ (Brazil). Dept. de Ciencias Naturais; Andrade, Cristina T. [Universidade Federal, Rio de Janeiro, RJ (Brazil). Inst. de Macromoleculas Professora Eloisa Mano]. E-mail: ctandrade@ima.ufrj.br

2006-09-15

The galactomannan from Prosopis juliflora (PJ galactomannan) was extracted from milled seeds in water at 50 deg C. Its structural and solution properties were characterised in comparison with a commercial sample of guar gum (GG galactomannan). After partial degradation, the resulting samples were submitted to {sup 13}C-NMR spectroscopy. The mannose to galactose (M/G) ratios of PJ (M/G = 1.64) and GG (M/G = 1.85) galactomannans were estimated from the relative peak areas of the corresponding C-1 lines. Expansion of the C-4 lines revealed differences in the fine structure of the two galactomannans. The intrinsic viscosity determined for the GG sample, [{eta}] = 10.3 dL g{sup -1}, was slightly higher than that determined for PJ galactomannan, [{eta}] = 9.4 dL g{sup -1}. Dynamic experiments carried out at the same concentrations showed similar viscoelastic behaviours for the two gums. No enhancement in the storage modulus (G') was observed for {kappa}-carrageenan/PJ mixed solution in 0.1 mol L{sup -1} KCl at 1.0 g L{sup -1} total polymer concentration, in relation to {kappa}-carrageenan alone. Self-supporting gels obtained by mixing {kappa}-carrageenan and PJ or GG galactomannans in 0.25 mol L{sup -1} KCl at 10 g L{sup -1} total polymer concentration displayed similar mechanical properties. (author)

Revisiting Kappa to account for change in the accuracy assessment of land-use models

NARCIS (Netherlands)

Vliet, van J.; Bregt, A.K.; Hagen-Zanker, A.

2011-01-01

Land-use change models are typically calibrated to reproduce known historic changes. Calibration results can then be assessed by comparing two datasets: the simulated land-use map and the actual land-use map at the same time. A common method for this is the Kappa statistic, which expresses the

Effect of apple extracts on NF-kappaB activation in human umbilical vein endothelial cells

Czech Academy of Sciences Publication Activity Database

Davis, P.A.; Polagruto, J.A.; Valacchi, G.; Phung, A.; Souček, Karel; Keen, C.L.; Gershwin, M.E.

2006-01-01

Roč. 231, č. 5 (2006), s. 594-598 ISSN 1535-3702 Institutional research plan: CEZ:AV0Z50040507 Keywords : human umbilical vascular endothelial cells * NF-kappaB * antioxidants Subject RIV: BO - Biophysics Impact factor: 2.845, year: 2006

NF-{kappa}B p50 promotes tumor cell invasion through negative regulation of invasion suppressor gene CRMP-1 in human lung adenocarcinoma cells

Energy Technology Data Exchange (ETDEWEB)

Ming, Gao [Cancer Research Center, College of Medicine, National Taiwan University, Taipei, Taiwan (China); National Center of Excellence for Clinical Trial and Research, National Taiwan University, Hospital, Taipei, Taiwan (China); Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Yeh, P Y [Cancer Research Center, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Department of Oncology, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 10016, Taiwan (China); Lu, Y -S [Cancer Research Center, College of Medicine, National Taiwan University, Taipei, Taiwan (China); National Center of Excellence for Clinical Trial and Research, National Taiwan University, Hospital, Taipei, Taiwan (China); Department of Oncology, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 10016, Taiwan, ROC (China); Chang, W C [Cancer Research Center, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Kuo, M -L [Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Cheng, A -L [Cancer Research Center, College of Medicine, National Taiwan University, Taipei, Taiwan (China); National Center of Excellence for Clinical Trial and Research, National Taiwan University, Hospital, Taipei, Taiwan (China); Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Department of Oncology, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 10016, Taiwan (China); Department of Internal Medicine, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 10016, Taiwan (China)], E-mail: alcheng@ntu.edu.tw

2008-11-14

Lung adenocarcinoma Cl1-5 cells were selected from parental Cl1-0 cells based on their high metastatic potential. In a previous study, CRMP-1, an invasion suppressor gene, was shown to be suppressed in Cl1-5 cells. However, the regulation of CRMP-1 expression has not been explored. In this study, we showed nuclear factor-{kappa}B controls CRMP-1 expression. The electromobility shift assay showed that while Cl1-0 cells exhibited low NF-{kappa}B activity in response to TNF-{alpha}, an abundance of basal and TNF-{alpha}-induced NF-{kappa}B-DNA complex was detected in Cl1-5 cells. Supershift-coupled EMSA and Western blotting of nuclear proteins, however, revealed p50 protein, but not classic p65/p50 heterodimer in the complex. ChIP and EMSA demonstrated that p50 binds to a {kappa}B site residing between -1753 and -1743 of the CRMP-1 promoter region. Transfection of antisense p50 gene into Cl1-5 cells increased the CRMP-1 protein level and decreased the invasive activity of Cl1-5 cells.

TEffect of nf-kappa B on diabetic retinopathy%NF-κB对糖尿病视网膜病变的影响

Institute of Scientific and Technical Information of China (English)

王爽; 宋子宣

2015-01-01

目的 研究和探讨核因子κB (NF-κ B)在糖尿病视网膜病变中的作用.方法 首先建立糖尿病视网膜病变(DR,diabetic retinopathy)动物模型,雄性SD大鼠,链脲佐菌素(streptozotocin,STZ) 60 mg/kg腹腔注射形成糖尿病模型,1.5个月后SD大鼠玻璃体内行血管内皮生长因子(VEGF)注射造成增殖型的糖尿病视网膜病变模型.视网膜铺片使用ADP酶染色视网膜血管,实时定量PCR检测NF-κ B表达量的变化,以及凋亡信号的检测.结果 视网膜血管染色的增殖面积造模给水组为(12.0±4.1)％,而视网膜血管染色的无灌注区面积造模给NF-κ B拮抗剂组为(37.9±3.9)％.正常组大鼠的NF-κ B蛋白的灰度值为(194.2890±3.8900),而造模给水组的NF-κB蛋白的灰度值为(74.4300±4.4900),凋亡实验结果显示正常组大鼠的凋亡信号个数平均为(32.2±3.1),而造模给水组的凋亡信号个数平均为(7.4±4.2).结论 NF-κB主要是通过引起细胞凋亡而减少糖尿病视网膜病变患者视网膜血管的增殖.%Objective To study the effect of nuclear factor kappa B (nf-kappa B) on diabetic retinopathy.Methods Diabetic retinopathy (DR,diabetic retinopathy) animal models were established.The SD rats intraperitoneal injected 60 cephalosporins (STZ streptozotocin) mg/kg to form diabetes models; 1.5 months from then,the SD rats were vitreously injected vascular endothelial growth factor (VEGF) to build models of proliferative diabetic retinopathy[l].Retinal blood vessels stained by ADP enzyme were used as retinal pave pieces.Real-time quantitative PCR was used to detect the e change of nf-kappa B expression quantity and apoptosis signal.Results The proliferation area of dyed retinal vessels of the model-buildingwith-water group was (12.0±4.1)％.The area without perfusion of dyed retinal blood vessels of the modelbuilding-with-nf-kappa-B-antagonist group was (37.9 ± 3.9)％.The gray value of nf-kappa B protein was (194.2890 ± 3.8900) in the

Simultaneous flow cytometric quantification of plant nuclear DNA contents over the full range of described angiosperm 2C values.

Science.gov (United States)

Galbraith, David W

2009-08-01

Flow cytometry provides a rapid, accurate, and simple means to determine nuclear DNA contents (C-value) within plant homogenates. This parameter is extremely useful in a number of applications in basic and applied plant biology; for example, it provides an important starting point for projects involving whole genome sequencing, it facilitates characterization of plant species within natural and agricultural settings, it allows facile identification of engineered plants that are euploid or that represent desired ploidy classes, it points toward studies concerning the role of C-value in plant growth and development and in response to the environment and in terms of evolutionary fitness, and, in uncovering new and unexpected phenomena (for example endoreduplication), it uncovers new avenues of scientific enquiry. Despite the ease of the method, C-values have been determined for only around 2% of the described angiosperm (flowering plant) species. Within this small subset, one of the most remarkable observations is the range of 2C values, which spans at least two orders of magnitude. In determining C-values for new species, technical issues are encountered which relate both to requirement for a method that can provide accurate measurements across this extended dynamic range, and that can accommodate the large amounts of debris which accompanies flow measurements of plant homogenates. In this study, the use of the Accuri C6 flow cytometer for the analysis of plant C-values is described. This work indicates that the unusually large dynamic range of the C6, a design feature, coupled to the linearity of fluorescence emission conferred by staining of nuclei using propidium iodide, allows simultaneous analysis of species whose C-values span that of almost the entire described angiosperms. Copyright 2009 International Society for Advancement of Cytometry.

MAML1 regulates cell viability via the NF-{kappa}B pathway in cervical cancer cell lines

Energy Technology Data Exchange (ETDEWEB)

Kuncharin, Yanin [Medical Microbiology Interdisciplinary Program, Graduate School, Chulalongkorn University, Payathai Road, Pathumwan, Bangkok 10330 (Thailand); Sangphech, Naunpun [Biotechnology Program, Faculty of Science, Chulalongkorn University, Payathai Road, Pathumwan, Bangkok 10330 (Thailand); Kueanjinda, Patipark [Medical Microbiology Interdisciplinary Program, Graduate School, Chulalongkorn University, Payathai Road, Pathumwan, Bangkok 10330 (Thailand); Bhattarakosol, Parvapan [Medical Microbiology Interdisciplinary Program, Graduate School, Chulalongkorn University, Payathai Road, Pathumwan, Bangkok 10330 (Thailand); Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Payathai Road, Pathumwan, Bangkok 10330 (Thailand); Palaga, Tanapat, E-mail: tanapat.p@chula.ac.th [Department of Microbiology, Faculty of Science, Chulalongkorn University, Payathai Road, Pathumwan, Bangkok 10330 (Thailand)

2011-08-01

The Notch signaling pathway plays important roles in tumorigenesis in a context-dependent manner. In human cervical cancer, alterations in Notch signaling have been reported, and both tumor-suppressing and tumor-promoting roles of Notch signaling have been proposed; however, the precise molecular mechanisms governing these roles in cervical cancer remain controversial. MAML is a transcriptional co-activator originally identified by its role in Notch signaling. Recent evidence suggests that it also plays a role in other signaling pathways, such as the p53 and {beta}-catenin pathways. MAML is required for stable formation of Notch transcriptional complexes at the promoters of Notch target genes. Chromosomal translocations affecting MAML have been shown to promote tumorigenesis. In this study, we used a truncated dominant-negative MAML1 (DN-MAML) to investigate the role of MAML in HPV-positive cervical cancer cell lines. Three human cervical cancer cell lines (HeLa, SiHa and CaSki) expressed all Notch receptors and the Notch target genes Hes1 and MAML1. Among these 3 cell lines, constitutive appearance of cleaved Notch1 was found only in CaSki cells, which suggests that Notch1 is constitutively activated in this cell line. Gamma secretase inhibitor (GSI) treatment, which suppresses Notch receptor activation, completely abrogated this form of Notch1 but had no effect on cell viability. Overexpression of DN-MAML by retroviral transduction in CaSki cells resulted in significant decreases in the mRNA levels of Hes1 and Notch1 but had no effects on the levels of MAML1, p53 or HPV E6/E7. DN-MAML expression induced increased viability of CaSki cells without any effect on cell cycle progression or cell proliferation. In addition, clonogenic assay experiments revealed that overexpression of DN-MAML resulted in increased colony formation compared to the overexpression of the control vector. When the status of the NF-{kappa}B pathway was investigated, CaSki cells overexpressing

Out-of-range international normalized ratio values and healthcare cost among new warfarin patients with non-valvular atrial fibrillation.

Science.gov (United States)

Nelson, Winnie W; Wang, Li; Baser, Onur; Damaraju, C V; Schein, Jeffrey R

2015-05-01

Patients with out-of-range international normalized ratio (INR) values 3.0 have been associated with increased risk of thromboembolic and bleeding events. INR monitoring is costly, because of associated physician and nurse time, laboratory resource use, and dose adjustments. This study assessed the healthcare cost burden associated with out-of-range INR among warfarin initiator patients diagnosed with non-valvular atrial fibrillation (NVAF) in the US Veterans Health Administration (VHA) population. Adult NVAF patients (≥18 years) initiating warfarin were selected from the VHA dataset for the study period October 1, 2007-September 30, 2012. Only valid INR measurements (0.5 ≤ INR ≤ 20) were examined for the follow-up period, from the index date (warfarin initiation date) until the end of warfarin exposure or death. All-cause healthcare costs within 30 days were measured starting from the second month (31 days post-index date) to the end of the study period. Costs for inpatient stays, emergency room, outpatient facility, physician office visits, and other services were computed separately. Multiple regression was performed using the generalized linear model for overall cost analysis. In total, 29,463 patients were included in the study sample. Mean costs for out-of-range INR ranged from $3419 to $5126. Inpatient, outpatient, outpatient pharmacy, and total costs were significantly higher after patients experienced out-of-range results (INR  3), compared with in-range INR (2 ≤ INR ≤ 3). When exposed to out-of-range INR, patients also incurred higher mean total costs within 2-6 months ($3840-$5820) than after the first 6 months ($2789-$3503) of warfarin therapy. In the VHA population, INR measures outside of the 2-3 range were associated with significantly higher healthcare costs. Increased costs were especially apparent when INR values were below 2, although INR measures above 3 were also associated with higher costs relative to in-range

[Nuclear factor-kappaB mRNA and protein expression in stomach tissue of rats with gastric ulcer recurrence and effect of jianwei yuyang granule on its expression].

Science.gov (United States)

Ling, Jiang-Hong; Li, Jia-Bang; Shen, Ding-Zhu; Zhou, Bing

2006-03-01

To observe the inflammatory reaction, nuclear factor-kappaB (NF-kappaB) mRNA and protein expression in stomach tissue of rats with gastric ulcer recurrence and the effect of Jianwei Yuyang granule (JYG) on them. Gastric ulcer and its recurrent lesion were successively induced by acetic acid and interliukin1-beta (IL-1beta), and the model rats were divided into the sham operation group, the model group, the omeprazole (correction of omepraxole) group and the JYG group to observe the state of chronic inflammatory cell, neutrophil count, NF-kappaBmRNA and protein expression in stomach tissue. On the 16th and 92th day after administration, the increase of chronic inflammatory cell, neutrophil, NF-kappaBmRNA and protein expression in the model group was more significant than those in the sham operated group (P ulcer induced by acetic acid. JYG may suppress inflammatory reaction by inhibiting the activation and expression of NF-kappaB in stomach tissue, which may be one of the mechanisms of JYG in preventing the recurrence of gastric ulcer.

Cytokine regulation of pro- and anti-apoptotic genes in rat hepatocytes: NF-kappaB-regulated inhibitor of apoptosis protein 2 (cIAP2) prevents apoptosis

NARCIS (Netherlands)

Schoemaker, Marieke H.; Ros, Jenny E.; Homan, Manon; Trautwein, Christian; Liston, Peter; Poelstra, Klaas; van Goor, Harry; Jansen, Peter L. M.; Moshage, Han

2002-01-01

BACKGROUND/AIMS: In acute liver failure, hepatocytes are exposed to various cytokines that activate both cell survival and apoptotic pathways. NF-kappaB is a central transcription factor in these responses. Recent studies indicate that blocking NF-kappaB causes apoptosis, indicating the existence of

Standardizing foot-type classification using arch index values.

Science.gov (United States)

Wong, Christopher Kevin; Weil, Rich; de Boer, Emily

2012-01-01

The lack of a reliable classification standard for foot type makes drawing conclusions from existing research and clinical decisions difficult, since different foot types may move and respond to treatment differently. The purpose of this study was to determine interrater agreement for foot-type classification based on photo-box-derived arch index values. For this correlational study with two raters, a sample of 11 healthy volunteers with normal to obese body mass indices was recruited from both a community weight-loss programme and a programme in physical therapy. Arch index was calculated using AutoCAD software from footprint photographs obtained via mirrored photo-box. Classification as high-arched, normal, or low-arched foot type was based on arch index values. Reliability of the arch index was determined with intra-class correlations; agreement on foot-type classification was determined using quadratic weighted kappa (κw). Average arch index was 0.215 for one tester and 0.219 for the second tester, with an overall range of 0.017 to 0.370. Both testers classified 6 feet as low-arched, 9 feet as normal, and 7 feet as high-arched. Interrater reliability for the arch index was ICC=0.90; interrater agreement for foot-type classification was κw=0.923. Classification of foot type based on arch index values derived from plantar footprint photographs obtained via mirrored photo-box showed excellent reliability in people with varying BMI. Foot-type classification may help clinicians and researchers subdivide sample populations to better differentiate mobility, gait, or treatment effects among foot types.

Standardizing Foot-Type Classification Using Arch Index Values

Science.gov (United States)

Weil, Rich; de Boer, Emily

2012-01-01

ABSTRACT Purpose: The lack of a reliable classification standard for foot type makes drawing conclusions from existing research and clinical decisions difficult, since different foot types may move and respond to treatment differently. The purpose of this study was to determine interrater agreement for foot-type classification based on photo-box-derived arch index values. Method: For this correlational study with two raters, a sample of 11 healthy volunteers with normal to obese body mass indices was recruited from both a community weight-loss programme and a programme in physical therapy. Arch index was calculated using AutoCAD software from footprint photographs obtained via mirrored photo-box. Classification as high-arched, normal, or low-arched foot type was based on arch index values. Reliability of the arch index was determined with intra-class correlations; agreement on foot-type classification was determined using quadratic weighted kappa (κw). Results: Average arch index was 0.215 for one tester and 0.219 for the second tester, with an overall range of 0.017 to 0.370. Both testers classified 6 feet as low-arched, 9 feet as normal, and 7 feet as high-arched. Interrater reliability for the arch index was ICC=0.90; interrater agreement for foot-type classification was κw=0.923. Conclusions: Classification of foot type based on arch index values derived from plantar footprint photographs obtained via mirrored photo-box showed excellent reliability in people with varying BMI. Foot-type classification may help clinicians and researchers subdivide sample populations to better differentiate mobility, gait, or treatment effects among foot types. PMID:23729964

[An exploratory study on the diagnostic cutoff value of International HIV-associated Dementia Scale in minority ethnic groups with different educational levels, in Guangxi].

Science.gov (United States)

Zhao, Ting-ting; Feng, Qi-ming; Liang, Hao; Tang, Xian-yan; Wei, Bo

2011-11-01

Using Intelligence Scale of Mini Mental State Estimated (MMSE) as the gold standard to determine the relevance of International HIV-associated Dementia Scale (IHDS) in minority ethnic areas in Guangxi populations with different cultural values. Corresponding boundary value related to the authenticity and reliability on IHDS were also evaluated. 200 patients with HIV infection were randomly selected from the minority ethnic groups in Guangxi. For each infected person, MMSE and IHDS blind scale were tested at the same period. Using the results from MMSE scale test as the gold standard, ROC curve and IHDS scale in Guangxi minority populations with different education levels which related to the diagnosis of dementia-HIV values were determined. The value of a specific sector under the IHDS sensitivity, specificity, and internal consistency coefficients was also evaluated. When considering the infected person did not differ on their educational level, the IHDS scale diagnostic cutoff appeared as 8.25, while IHDS sensitivity as 0.925, specificity as 0.731 and Kappa as 0.477 (P education groups showed different IHDS diagnostic cutoff values. People with high school, secondary school or higher education levels, the IHDS diagnosis appeared to be 8.25, when sensitivity was 0.917, specificity was 0.895 and Kappa was 0.722 (P education level, the IHDS appeared to be 7.25. When sensitivity was 0.875, specificity was 0.661 and Kappa was 0.372 (P value (IHDS ≤ 10 points). When using IHDS to perform the HIV related dementia screening program, in the minority areas of Guangxi, culture context, the degree and difference of HIV infection should be considered, especially in using IHDS diagnostic cutoff values.

[Diagnostic value of Vanderbilt ADHD Parent Rating Scale in attention deficit hyperactivity disorder].

Science.gov (United States)

Xiao, Zhao-Hua; Wang, Qing-Hong; Luo, Tian-Tian; Zhong, Le

2013-05-01

To study the value of the Vanderbilt ADHD Parent Rating Scale (VADPRS) in the diagnosis of attention deficit hyperactivity disorder (ADHD). VADPRS were completed by parents of 319 children with suspected ADHD. The children were then evaluated by a specialist based on the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) and 196 of them were diagnosed with ADHD. The value of VADPRS in the diagnosis of attention deficit and hyperactivity was evaluated using ROC curves. Diagnostic evaluation indexes at best operating point were calculated. Kappa values were calculated to explore the consistency of items in VADPRS and corresponding items in the DSM-IV criteria. The area under the ROC curve for the diagnosis of attention deficit by VADPRS was 0.791. At the best operating point, its sensitivity was 0.83, specificity was 0.63, positive predictive value was 0.69 and negative predictive value was 0.79. The area under the ROC curve for the diagnosis of hyperactivity by VADPRS was 0.855. At the best operating point, its sensitivity was 0.82, specificity was 0.76, positive predictive value was 0.65, and negative predictive value was 0.88. The negative predictive value of VADPRS in general population screen was 0.99, based on the results of this study. The consistency of items in the VADPRS and corresponding items in DSM-Ⅳ criteria was poor, with the Kappa value of most items being less than 0.40. VADPRS is suitable for a general population screen for ADHD and it is helpful in the clinical diagnosis of ADHD, but its results can be influenced by parents' awareness and perception of children's behavior, and cannot replace the interview and judgment of professionals.

Combined estimation of kappa and shear-wave velocity profile of the Japanese rock reference

Science.gov (United States)

Poggi, Valerio; Edwards, Benjamin; Fäh, Donat

2013-04-01

the retrieval of the shape of the velocity profile that is characterized by no relative amplification within the network. Subsequently, the contribution of intrinsic attenuation is analyzed, disaggregated from the anelastic function by using the frequency independent (and site-dependent) attenuation operator kappa (κ). By comparing the dependency of κ with the quarter-wavelength velocity at selected sites, a frequency-dependent predictive equation is established to model the attenuation characteristics of an arbitrary rock or stiff-soil velocity model, such as the reference model obtained in the first step. The result of this application can be used to model the site-dependent attenuation for any rock and stiff-soil site for which an estimation of the velocity profile or its corresponding quarter-wavelength velocity representation is available. As an additional output of the present study, we also propose a simplified method to estimate kappa from the average velocity estimates over the first 30m (Vs30). We provide an example of such predictions for a range of Vs30 velocities up to 2000m/s.

Resveratrol enhances ultraviolet B-induced cell death through nuclear factor-{kappa}B pathway in human epidermoid carcinoma A431 cells

Energy Technology Data Exchange (ETDEWEB)

Roy, Preeti; Kalra, Neetu; Nigam, Nidhi; George, Jasmine [Proteomics Laboratory, Indian Institute of Toxicology Research (CSIR), P.O. Box 80, M.G. Marg, Lucknow 226 001 (India); Ray, Ratan Singh; Hans, Rajendra K. [Photobiology Laboratory, Indian Institute of Toxicology Research (CSIR), P.O. Box 80, M.G. Marg, Lucknow 226 001 (India); Prasad, Sahdeo [Proteomics Laboratory, Indian Institute of Toxicology Research (CSIR), P.O. Box 80, M.G. Marg, Lucknow 226 001 (India); Shukla, Yogeshwer, E-mail: yogeshwer_shukla@hotmail.com [Proteomics Laboratory, Indian Institute of Toxicology Research (CSIR), P.O. Box 80, M.G. Marg, Lucknow 226 001 (India)

2009-06-26

Resveratrol has been reported to suppress cancer progression in several in vivo and in vitro models, whereas ultraviolet B (UVB), a major risk for skin cancer, is known to induce cell death in cancerous cells. Here, we investigated whether resveratrol can sensitize A431 human epidermoid carcinoma cells to UVB-induced cell death. We examined the combined effect of UVB (30 mJ/cm{sup 2}) and resveratrol (60 {mu}M) on A431 cells. Exposure of A431 carcinoma cells to UVB radiation or resveratrol can inhibit cell proliferation and induce apoptosis. However, the combination of resveratrol and UVB exposure was associated with increased proliferation inhibition of A431 cells compared with either agent alone. Furthermore, results showed that resveratrol and UVB treatment of A431 cells disrupted the nuclear factor-kappaB (NF-{kappa}B) pathway by blocking phosphorylation of serine 536 and inactivating NF-{kappa}B and subsequent degradation of I{kappa}B{alpha}, which regulates the expression of survivin. Resveratrol and UVB treatment also decreased the phosphorylation of tyrosine 701 of the important transcription factor signal transducer activator of transcription (STAT1), which in turn inhibited translocation of phospho-STAT1 to the nucleus. Moreover, resveratrol/UVB also inhibited the metastatic protein LIMK1, which reduced the motility of A431 cells. In conclusion, our study demonstrates that the combination of resveratrol and UVB act synergistically against skin cancer cells. Thus, resveratrol is a potential chemotherapeutic agent against skin carcinogenesis.

Induction of activator protein (AP)-1 and nuclear factor-kappaB by CD28 stimulation involves both phosphatidylinositol 3-kinase and acidic sphingomyelinase signals.

Science.gov (United States)

Edmead, C E; Patel, Y I; Wilson, A; Boulougouris, G; Hall, N D; Ward, S G; Sansom, D M

1996-10-15

A major obstacle in understanding the signaling events that follow CD28 receptor ligation arises from the fact that CD28 acts as a costimulus to TCR engagement, making it difficult to assess the relative contribution of CD28 signals as distinct from those of the TCR. To overcome this problem, we have exploited the observation that activated human T cell blasts can be stimulated via the CD28 surface molecule in the absence of antigenic challenge; thus, we have been able to observe the response of normal T cells to CD28 activation in isolation. Using this system, we observed that CD28 stimulation by B7-transfected CHO cells induced a proliferative response in T cells that was not accompanied by measurable IL-2 production. However, subsequent analysis of transcription factor generation revealed that B7 stimulation induced both activator protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB) complexes, but not NF-AT. In contrast, engagement of the TCR by class II MHC/superantigen, either with or without CD28 ligation, resulted in the induction of NF-AT, AP-1, and NF-kappaB as well as IL-2 production. Using selective inhibitors, we investigated the signaling pathways involved in the CD28-mediated induction of AP-1 and NF-kappaB. This revealed that NF-kappaB generation was sensitive to chloroquine, an inhibitor of acidic sphingomyelinase, but not to the phosphatidylinositol 3-kinase inhibitor, wortmannin. In contrast, AP-1 generation was inhibited by wortmannin and was also variably sensitive to chloroquine. These data suggest that in activated normal T cells, CD28-derived signals can stimulate proliferation at least in part via NF-kappaB and AP-1 generation, and that this response uses both acidic sphingomyelinase and phosphatidylinositol 3-kinase-linked pathways.

Bacterial endotoxin enhances colorectal cancer cell adhesion and invasion through TLR-4 and NF-kappaB-dependent activation of the urokinase plasminogen activator system.

LENUS (Irish Health Repository)

Killeen, S D

2009-05-19

Perioperative exposure to lipopolysaccharide (LPS) is associated with accelerated metastatic colorectal tumour growth. LPS directly affects cells through Toll-like receptor 4 (TLR-4) and the transcription factor NF-kappaB. The urokinase plasminogen activator (u-PA) system is intimately implicated in tumour cell extracellular matrix (ECM) interactions fundamental to tumour progression. Thus we sought to determine if LPS directly induces accelerated tumour cell ECM adhesion and invasion through activation of the u-PA system and to elucidate the cellular pathways involved. Human colorectal tumour cell lines were stimulated with LPS. u-PA concentration, u-PA activity, active u-PA, surface urokinase plasminogen activator receptor (u-PAR) and TLR-4 expression were assessed by ELISA, colorimetric assay, western blot analysis and flow cytometry respectively. In vitro tumour cell vitronectin adhesion and ECM invasion were analysed by vitronectin adhesion assay and ECM invasion chambers. u-PA and u-PAR function was inhibited with anti u-PA antibodies or the selective u-PA inhibitors amiloride or WXC-340, TLR-4 by TLR-4-blocking antibodies and NF-kappaB by the selective NF-kappaB inhibitor SN-50. LPS upregulates u-PA and u-PAR in a dose-dependent manner, enhancing in vitro tumour cell vitronectin adhesion and ECM invasion by >40% (P<0.01). These effects were ameliorated by u-PA and u-PAR inhibition. LPS activates NF-kappaB through TLR-4. TLR-4 and NF-kappaB inhibition ameliorated LPS-enhanced u-PA and u-PAR expression, tumour cell vitronectin adhesion and ECM invasion. LPS promotes tumour cell ECM adhesion and invasion through activation of the u-PA system in a TLR-4- and NF-kappaB-dependent manner.

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

Science.gov (United States)

Csaki, Constanze; Mobasheri, Ali; Shakibaei, Mehdi

2009-01-01

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

[Joint diagnostic value of four temperature sensation tests in elderly patients with type 2 diabetic peripheral neuropathy].

Science.gov (United States)

Guo, Wei; Li, Yun-Ming; Ai, Zhi-Hua; You, Zhi-Qing; Wan, Yong; Cheng, Ying; Lang, Hong-Mei

2013-07-01

To explore the joint diagnostic value of four temperature sensation tests in elderly patients with type 2 diabetic peripheral neuropathy. Thermal sensory analyzer-II were applied to measure cool sensation (CS), warm sensation (WS), cold pain sensation (CP)and heat pain sensation (HP) of 308 elderly patients with type 2 diabetes. Logistic regression model was adopted to create the new variable Temp4 from four temperature sensation tests to diagnose type 2 diabetic peripheral neuropathy. The ROC curve analysis was used to determine the best cut-off points of the four temperature sensation and Temp4, and the diagnostic value of it was evaluated. The means of temperature sensation tests of the diabetic peripheral neuropathy (DPN) group were significantly different from those of the non-DPN group (P sensation tests to diagnose the DPN, the sensitivity of WS test was the highest, and the value was 0.710; but the specificity, positive predictive value, negative predictive value, Youden index, diagnostic accuracy and Kappa value of cold sensation test were the highest, and the values were 0.842, 0.746, 0.799, 0.528, 77.92% and 0.535, respectively; the Kappa values of the other three temperature sensation tests were all greater than 0.4 (P sensation tests (P sensation quantitative tests were in good agreementand could be applied to diagnose DPN; the new variable Temp4 could be used for diagnosis of DPN with a higher diagnostic accuracy.

Comparación de las medidas del ángulo kappa realizadas mediante pupilometría y topografía corneal

OpenAIRE

Marcos Pérez, Mario

2016-01-01

El ojo no es un sistema óptico centrado, por ello surge la necesidad de definir ejes visuales. El ángulo kappa está formado entre el eje pupilar y la línea de mirada, es un parámetro mensurable y relevante a la hora de afrontar cirugía refractiva. El objetivo del trabajo es demostrar la intercambiabilidad de las medidas de kappa con los dispositivos Galilei G4 y Allegro Topolyzer. En la literatura no se encuentra un estudio similar, con lo que resulta conveniente. Para ello se realizan medida...

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)

2017-02-15

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.)

Tomosynthesis of the thoracic spine: added value in diagnosing vertebral fractures in the elderly

International Nuclear Information System (INIS)

Geijer, Mats; Gunnlaugsson, Eirikur; Goetestrand, Simon; Weber, Lars; Geijer, Haakan

2017-01-01

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 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.)

Noncommutative differential forms on the kappa-deformed space

International Nuclear Information System (INIS)

Meljanac, Stjepan; Kresic-Juric, Sasa

2009-01-01

We construct a differential algebra of forms on the kappa-deformed space. For a given realization of noncommutative coordinates as formal power series in the Weyl algebra we find an infinite family of one-forms and nilpotent exterior derivatives. We derive explicit expressions for the exterior derivative and one-forms in covariant and noncovariant realizations. We also introduce higher order forms and show that the exterior derivative satisfies the graded Leibniz rule. The differential forms are generally not graded commutative, but they satisfy the graded Jacobi identity. We also consider the star-product of classical differential forms. The star-product is well defined if the commutator between the noncommutative coordinates and one-forms is closed in the space of one-forms alone. In addition, we show that in certain realizations the exterior derivative acting on the star-product satisfies the undeformed Leibniz rule.

Kinetic Alfven wave in the presence of kappa distribution function in plasma sheet boundary layer

Energy Technology Data Exchange (ETDEWEB)

Shrivastava, G., E-mail: geetphy9@gmail.com; Ahirwar, G. [School of Studies in Physics, Vikram University, Ujjain India (India); Shrivastava, J., E-mail: jayashrivastava2007@gmail.com [Dronacharya Group of Institutions, Greater Noida-India (India)

2015-07-31

The particle aspect approach is adopted to investigate the trajectories of charged particles in the electromagnetic field of kinetic Alfven wave. Expressions are found for the dispersion relation, damping/growth rate and associated currents in the presence of kappa distribution function. Kinetic effect of electrons and ions are included to study kinetic Alfven wave because both are important in the transition region. It is found that the ratio β of electron thermal energy density to magnetic field energy density and the ratio of ion to electron thermal temperature (T{sub i}/T{sub e}), and kappa distribution function affect the dispersion relation, damping/growth rate and associated currents in both cases(warm and cold electron limit).The treatment of kinetic Alfven wave instability is based on assumption that the plasma consist of resonant and non resonant particles. The resonant particles participate in an energy exchange process, whereas the non resonant particles support the oscillatory motion of the wave.

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

Energy Technology Data Exchange (ETDEWEB)

Kang, Myoung Hee [Graduate School of Medicine, Korea University College of Medicine, Korea University, Seoul 136-705 (Korea, Republic of); Oh, Sang Cheul [Division of Oncology/Hematology, Department of Internal Medicine, Korea University College of Medicine, Korea University, Seoul 136-705 (Korea, Republic of); Lee, Hyun Joo [Department of Pathology, Korea University College of Medicine, Korea University, Seoul 136-705 (Korea, Republic of); Kang, Han Na; Kim, Jung Lim [Graduate School of Medicine, Korea University College of Medicine, Korea University, Seoul 136-705 (Korea, Republic of); Kim, Jun Suk [Division of Oncology/Hematology, Department of Internal Medicine, Korea University College of Medicine, Korea University, Seoul 136-705 (Korea, Republic of); Yoo, Young A., E-mail: ydanbi@korea.ac.kr [Brain Korea 21 Program for Biomedical Science, Korea University College of Medicine, Korea University, Seoul 136-705 (Korea, Republic of)

2011-07-15

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

Two specific drugs, BMS-345541 and purvalanol A induce apoptosis of HTLV-1 infected cells through inhibition of the NF-kappaB and cell cycle pathways.

Science.gov (United States)

Agbottah, Emmanuel; Yeh, Wen-I; Berro, Reem; Klase, Zachary; Pedati, Caitlin; Kehn-Hall, Kyleen; Wu, Weilin; Kashanchi, Fatah

2008-06-10

Human T-cell leukemia virus type-1 (HTLV-1) induces adult T-cell leukemia/lymphoma (ATL/L), a fatal lymphoproliferative disorder, and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a chronic progressive disease of the central nervous system after a long period of latent infection. Although the mechanism of transformation and leukemogenesis is not fully elucidated, there is evidence to suggest that the viral oncoprotein Tax plays a crucial role in these processes through the regulation of several pathways including NF-kappaB and the cell cycle pathways. The observation that NF-kappaB, which is strongly induced by Tax, is indispensable for the maintenance of the malignant phenotype of HTLV-1 by regulating the expression of various genes involved in cell cycle regulation and inhibition of apoptosis provides a possible molecular target for these infected cells. To develop potential new therapeutic strategies for HTLV-1 infected cells, in this present study, we initially screened a battery of NF-kappaB and CDK inhibitors (total of 35 compounds) to examine their effects on the growth and survival of infected T-cell lines. Two drugs namely BMS-345541 and Purvalanol A exhibited higher levels of growth inhibition and apoptosis in infected cell as compared to uninfected cells. BMS-345541 inhibited IKKbeta kinase activity from HTLV-1 infected cells with an IC50 (the 50% of inhibitory concentration) value of 50 nM compared to 500 nM from control cells as measured by in vitro kinase assays. The effects of Purvalanol A were associated with suppression of CDK2/cyclin E complex activity as previously shown by us. Combination of both BMS-345541 and Purvalanol A showed a reduced level of HTLV-1 p19 Gag production in cell culture. The apparent apoptosis in these infected cells were associated with increased caspase-3 activity and PARP cleavage. The potent and selective apoptotic effects of these drugs suggest that both BMS-345541 and Purvalanol A, which target

Selection of antigenic markers on a GFP-C{kappa} fusion scaffold with high sensitivity by eukaryotic ribosome display

Energy Technology Data Exchange (ETDEWEB)

Yongmin, Yang [Institute of Genetics, San Diego, CA 92121-2233 (United States); IgE Therapeutics, Inc., San Diego, CA 92121-2233 (United States); Barankiewicz, Teresa J [Institute of Genetics, San Diego, CA 92121-2233 (United States); IgE Therapeutics, Inc., San Diego, CA 92121-2233 (United States); Mingyue, He [Babraham Institute, Cambridge CB2 4AT (United Kingdom); Taussig, Michael J [Babraham Institute, Cambridge CB2 4AT (United Kingdom); Chen, Swey-Shen [Institute of Genetics, San Diego, CA 92121-2233 (United States) and IgE Therapeutics, Inc., San Diego, CA 92121-2233 (United States)

2007-07-27

Ribosome display is a cell-free system permitting gene selection through the physical association of genetic material (mRNA) and its phenotypic (protein) product. While often used to select single-chain antibodies from large libraries by panning against immobilized antigens, we have adapted ribosome display for use in the 'reverse' format in order to select high affinity antigenic determinants against solid-phase antibody. To create an antigenic scaffold, DNA encoding green fluorescent protein (GFP) was fused to a light chain constant domain (C{kappa}) with stop codon deleted, and with 5' signals (T7 promoter, Kozak) enabling coupled transcription/translation in a eukaryotic cell-free system. Epitopes on either GFP (5') or C{kappa} (3') were selected by anti-GFP or anti-C{kappa} antibodies, respectively, coupled to magnetic beads. After selection, mRNA was amplified directly from protein-ribosome-mRNA (PRM) complexes by in situ PCR followed by internal amplification and reassembly PCR. As little as 10 fg of the 1 kb DNA construct, i.e. approximately 7500 molecules, could be recovered following a single round of interaction with solid-phase anti-GFP antibody. This platform is highly specific and sensitive for the antigen-antibody interaction and may permit selection and reshaping of high affinity antigenic variants of scaffold proteins.

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

Science.gov (United States)

Silbermann, Katrin; Schneider, Grit; Grassmann, Ralph

2008-11-01

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

Real-time monitoring of inflammation status in 3T3-L1 adipocytes possessing a secretory Gaussia luciferase gene under the control of nuclear factor-kappa B response element

Energy Technology Data Exchange (ETDEWEB)

Nagasaki, Haruka; Yoshimura, Takeshi [Department of Life Sciences, Graduate School of Bioresources, Mie University, Tsu 514-8507 (Japan); Aoki, Naohito, E-mail: n-aoki@bio.mie-u.ac.jp [Department of Life Sciences, Graduate School of Bioresources, Mie University, Tsu 514-8507 (Japan)

2012-04-13

Highlights: Black-Right-Pointing-Pointer Inflammation status in adipocytes can be monitored by the new assay system. Black-Right-Pointing-Pointer Only an aliquot of conditioned medium is required without cell lysis. Black-Right-Pointing-Pointer Inflammation-attenuating compounds can be screened more conveniently. -- Abstract: We have established 3T3-L1 cells possessing a secretory Gaussia luciferase (GLuc) gene under the control of nuclear factor-kappa B (NF-{kappa}B) response element. The 3T3-L1 cells named 3T3-L1-NF-{kappa}B-RE-GLuc could differentiate into adipocyte as comparably as parental 3T3-L1 cells. Inflammatory cytokines such as tumor necrosis factor (TNF)-{alpha} and interleukin (IL)-1{beta} induced GLuc secretion of 3T3-L1-NF-{kappa}B-RE-GLuc adipocytes in a concentration- and time-dependent manner. GLuc secretion of 3T3-L1-NF-{kappa}B-RE-GLuc adipocytes was also induced when cultured with RAW264.7 macrophages and was dramatically enhanced by lipopolysaccharide (LPS)-activated macrophages. An NF-{kappa}B activation inhibitor BAY-11-7085 and an antioxidant N-acetyl cysteine significantly suppressed GLuc secretion induced by macrophages. Finally, we found that rosemary-derived carnosic acid strongly suppressed GLuc secretion induced by macrophages and on the contrary up-regulated adiponectin secretion. Collectively, by using 3T3-L1-NF-{kappa}B-RE-GLuc adipocytes, inflammation status can be monitored in real time and inflammation-attenuating compounds can be screened more conveniently.

Vergleichende Analyse der Expression des Glukokortikoid-Rezeptors und der NF-kappaB Untereinheit p50 in Lymphozyten von Patienten mit rheumatoider Arthritis und Gesunden

OpenAIRE

Klüter, Andreas

2003-01-01

Zielstellung: Es wurden die Expression des antiinflammatorisch wirkenden Transkriptionsfaktors Glukokortikoid-Rezeptor (GR) und der Untereinheit p50 des proinflammatorischen Transkriptionsfaktor NF-kappaB in peripheren mononuklearen Blutzellen (PBMC) von Patienten mit rheumatoider Arthritis (RA) untersucht. Methode: Es wurden unbehandelte und mit Glukokortikoiden vorbehandelte RA-Patienten sowie gesunde Probanden verglichen. Die Expressionsanalyse von GR und der NF-kappaB Untereinheit p50 ...

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

2013-01-01

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

Carbachol ameliorates lipopolysaccharide-induced intestinal epithelial tight junction damage by down-regulating NF-{kappa}{beta} and myosin light-chain kinase pathways

Energy Technology Data Exchange (ETDEWEB)

Zhang, Ying [Department of Anesthesia, Critical Care Medicine and Emergency Medicine Center, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei Province, People' s Republic of China (China); Li, Jianguo, E-mail: 2010lijianguo@sina.cn [Department of Anesthesia, Critical Care Medicine and Emergency Medicine Center, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei Province, People' s Republic of China (China)

2012-11-16

Highlights: Black-Right-Pointing-Pointer Carbachol reduced the lipopolysaccharide-induced intestinal barrier breakdown. Black-Right-Pointing-Pointer Carbachol ameliorated the lipopolysaccharide-induced ileal tight junction damage. Black-Right-Pointing-Pointer Carbachol prevented the LPS-induced NF-{kappa}{beta} and myosin light-chain kinase activation. Black-Right-Pointing-Pointer Carbachol exerted its beneficial effects in an {alpha}7 nicotinic receptor-dependent manner. -- Abstract: Carbachol is a cholinergic agonist that protects the intestines after trauma or burn injury. The present study determines the beneficial effects of carbachol and the mechanisms by which it ameliorates the lipopolysaccharide (LPS)-induced intestinal barrier breakdown. Rats were injected intraperitoneally with 10 mg/kg LPS. Results showed that the gut barrier permeability was reduced, the ultrastructural disruption of tight junctions (TJs) was prevented, the redistribution of zonula occludens-1 and claudin-2 proteins was partially reversed, and the nuclear factor-kappa beta (NF-{kappa}{beta}) and myosin light-chain kinase (MLCK) activation in the intestinal epithelium were suppressed after carbachol administration in LPS-exposed rats. Pretreatment with the {alpha}7 nicotinic acetylcholine receptor ({alpha}7nAchR) antagonist {alpha}-bungarotoxin blocked the protective action of carbachol. These results suggested that carbachol treatment can protect LPS-induced intestinal barrier dysfunction. Carbachol exerts its beneficial effect on the amelioration of the TJ damage by inhibiting the NF-{kappa}{beta} and MLCK pathways in an {alpha}7nAchR-dependent manner.

Oleamide suppresses lipopolysaccharide-induced expression of iNOS and COX-2 through inhibition of NF-kappaB activation in BV2 murine microglial cells.

Science.gov (United States)

Oh, Young Taek; Lee, Jung Yeon; Lee, Jinhwa; Lee, Ju Hie; Kim, Ja-Eun; Ha, Joohun; Kang, Insug

2010-05-03

Oleamide (cis-9-octadecenamide) is an endogenous sleep-inducing fatty acid amide that accumulates in the cerebrospinal fluid of the sleep-deprived animals. Microglia are the major immune cells involved in neuroinflammation causing brain damage during infection, ischemia, and neurodegenerative disease. In this study, we examined the effects of oleamide on LPS-induced production of proinflammatory mediators and the mechanisms involved in BV2 microglia. Oleamide inhibited LPS-induced production of NO and prostaglandin E2 as well as expression of iNOS and COX-2. We showed that oleamide blocked LPS-induced NF-kappaB activation and phosphorylation of inhibitor kappaB kinase (IKK). We also showed that oleamide inhibited LPS-induced phosphorylation of Akt, p38 MAPK, and ERK, activation of PI 3-kinase, and accumulation of reactive oxygen species (ROS). Finally, we showed that a specific antagonist of the CB2 receptor, AM630, blocked the inhibitory effects of oleamide on LPS-induced production of proinflammatory mediators and activation of NF-kappaB. Taken together, our results suggest that oleamide shows an anti-inflammatory effect through inhibition of NF-kappaB activation in LPS-stimulated BV2 microglia. 2010 Elsevier Ireland Ltd. All rights reserved.

Arthroscopy vs. MRI for a detailed assessment of cartilage disease in osteoarthritis: diagnostic value of MRI in clinical practice

Directory of Open Access Journals (Sweden)

Haage Patrick

2010-04-01

Full Text Available Abstract Background In patients with osteoarthritis, a detailed assessment of degenerative cartilage disease is important to recommend adequate treatment. Using a representative sample of patients, this study investigated whether MRI is reliable for a detailed cartilage assessment in patients with osteoarthritis of the knee. Methods In a cross sectional-study as a part of a retrospective case-control study, 36 patients (mean age 53.1 years with clinically relevant osteoarthritis received standardized MRI (sag. T1-TSE, cor. STIR-TSE, trans. fat-suppressed PD-TSE, sag. fat-suppressed PD-TSE, Siemens Magnetom Avanto syngo MR B 15 on a 1.5 Tesla unit. Within a maximum of three months later, arthroscopic grading of the articular surfaces was performed. MRI grading by two blinded observers was compared to arthroscopic findings. Diagnostic values as well as intra- and inter-observer values were assessed. Results Inter-observer agreement between readers 1 and 2 was good (kappa = 0.65 within all compartments. Intra-observer agreement comparing MRI grading to arthroscopic grading showed moderate to good values for readers 1 and 2 (kappa = 0.50 and 0.62, respectively, the poorest being within the patellofemoral joint (kappa = 0.32 and 0.52. Sensitivities were relatively low at all grades, particularly for grade 3 cartilage lesions. A tendency to underestimate cartilage disorders on MR images was not noticed. Conclusions According to our results, the use of MRI for precise grading of the cartilage in osteoarthritis is limited. Even if the practical benefit of MRI in pretreatment diagnostics is unequivocal, a diagnostic arthroscopy is of outstanding value when a grading of the cartilage is crucial for a definitive decision regarding therapeutic options in patients with osteoarthritis.

Biopolymer electrolytes based on blend of kappa-carrageenan and cellulose derivatives for potential application in dye sensitized solar cell

International Nuclear Information System (INIS)

Rudhziah, S.; Ahmad, A.; Ahmad, I.; Mohamed, N.S.

2015-01-01

In this work, carboxymethyl kappa-carrageenan was used as the principle host for developing new biopolymer electrolytes based on the blend of carboxymethyl kappa-carrageenan/carboxymethyl cellulose. The blending of carboxymethyl cellulose into carboxymethyl kappa-carragenan was found to be a promising strategy to improve the material properties such as conductive properties. The electrolyte samples were characterized using Fourier transform infrared spectroscopy, scanning electron microscopy, dynamic mechanical analysis, electrochemical impedance spectroscopy, ionic transference number measurement and linear sweep voltammetry in order to investigate their structural, thermal and electrochemical properties. Impedance study showed that the ionic conductivity increased with the increment of ammonium iodide concentration. The highest room temperature ionic conductivity achieved was 2.41 × 10 −3 S cm −1 at 30 wt% of the salt. The increment of conductivity was due to the increase of formation of transient cross-linking between the carboxymethyl kappa-carrageenan/carboxymethyl cellulose chains and the doping salt as indicated the T g trend. The conductivity was also attributed by the increase in the number of charge carriers in the biopolymer electrolytes system. The interactions between polymers and salt were confirmed by FTIR study. The transference number measurements showed that the conductivity was predominantly ionic. Temperature dependent conductivity study showed that conductivity increased with the reciprocal of temperature. The conductivity-temperature plots suggested that the conductivity obeyed the Vogel–Tammann–Fulcher relation and the activation energy for the best conducting sample was 0.010 eV. This system was used for the fabrication of dye sensitized solar cells, FTO/TiO 2 -dye/CMKC/CMCE-NH 4 I + I 2 /Pt. The fabricated cell showed response under light intensity of 100 mW cm −2 with efficiency of 0.13% indicating that the blend biopolymer

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

Science.gov (United States)

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

2015-12-17

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

Sex Differences in Kappa Opioid Receptor Function and Their Potential Impact on Addiction

OpenAIRE

Chartoff, Elena H.; Mavrikaki, Maria

2015-01-01

Behavioral, biological, and social sequelae that lead to drug addiction differ between men and women. Our efforts to understand addiction on a mechanistic level must include studies in both males and females. Stress, anxiety, and depression are tightly linked to addiction, and whether they precede or result from compulsive drug use depends on many factors, including biological sex. The neuropeptide dynorphin (DYN), an endogenous ligand at kappa opioid receptors (KORs), is necessary for stress...

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

DEFF Research Database (Denmark)

Jiang, Y P; Wang, H; D'Eustachio, P

1993-01-01

We describe a new member of the receptor protein tyrosine phosphatase family, R-PTP-kappa, cDNA cloning predicts that R-PTP-kappa is synthesized from a precursor protein of 1,457 amino acids. Its intracellular domain displays the classical tandemly repeated protein tyrosine phosphatase homology, ...

Inter-observer agreement for abdominal CT in unselected patients with acute abdominal pain

International Nuclear Information System (INIS)

Randen, Adrienne van; Lameris, Wytze; Nio, C.Y.; Spijkerboer, Anje M.; Meier, Mark A.; Tutein Nolthenius, Charlotte; Smithuis, Frank; Stoker, Jaap; Bossuyt, Patrick M.; Boermeester, Marja A.

2009-01-01

The level of inter-observer agreement of abdominal computed tomography (CT) in unselected patients presenting with acute abdominal pain at the Emergency Department (ED) was evaluated. Two hundred consecutive patients with acute abdominal pain were prospectively included. Multi-slice CT was performed in all patients with intravenous contrast medium only. Three radiologists independently read all CT examinations. They recorded specific radiological features and a final diagnosis on a case record form. We calculated the proportion of agreement and kappa values, for overall, urgent and frequently occurring diagnoses. The mean age of the evaluated patients was 46 years (range 19-94), of which 54% were women. Overall agreement on diagnoses was good, with a median kappa of 0.66. Kappa values for specific urgent diagnoses were excellent, with median kappa values of 0.84, 0.90 and 0.81, for appendicitis, diverticulitis and bowel obstruction, respectively. Abdominal CT has good inter-observer agreement in unselected patients with acute abdominal pain at the ED, with excellent agreement for specific urgent diagnoses as diverticulitis and appendicitis. (orig.)

Inter-observer agreement for abdominal CT in unselected patients with acute abdominal pain

Energy Technology Data Exchange (ETDEWEB)

Randen, Adrienne van [University of Amsterdam, Department of Radiology, Academic Medical Center, Amsterdam (Netherlands); University of Amsterdam, Department of Surgery, Academic Medical Center, Amsterdam (Netherlands); Academic Medical Center, Amsterdam (Netherlands); Lameris, Wytze [University of Amsterdam, Department of Radiology, Academic Medical Center, Amsterdam (Netherlands); University of Amsterdam, Department of Surgery, Academic Medical Center, Amsterdam (Netherlands); Nio, C.Y.; Spijkerboer, Anje M.; Meier, Mark A.; Tutein Nolthenius, Charlotte; Smithuis, Frank; Stoker, Jaap [University of Amsterdam, Department of Radiology, Academic Medical Center, Amsterdam (Netherlands); Bossuyt, Patrick M. [University of Amsterdam, Department of Clinical Epidemiology, Biostatistics, and Bioinformatics, Academic Medical Center, Amsterdam (Netherlands); Boermeester, Marja A. [University of Amsterdam, Department of Surgery, Academic Medical Center, Amsterdam (Netherlands)

2009-06-15

The level of inter-observer agreement of abdominal computed tomography (CT) in unselected patients presenting with acute abdominal pain at the Emergency Department (ED) was evaluated. Two hundred consecutive patients with acute abdominal pain were prospectively included. Multi-slice CT was performed in all patients with intravenous contrast medium only. Three radiologists independently read all CT examinations. They recorded specific radiological features and a final diagnosis on a case record form. We calculated the proportion of agreement and kappa values, for overall, urgent and frequently occurring diagnoses. The mean age of the evaluated patients was 46 years (range 19-94), of which 54% were women. Overall agreement on diagnoses was good, with a median kappa of 0.66. Kappa values for specific urgent diagnoses were excellent, with median kappa values of 0.84, 0.90 and 0.81, for appendicitis, diverticulitis and bowel obstruction, respectively. Abdominal CT has good inter-observer agreement in unselected patients with acute abdominal pain at the ED, with excellent agreement for specific urgent diagnoses as diverticulitis and appendicitis. (orig.)

Biochemical and hematologic reference values for free-ranging, chemically immobilized wild norwegian reindeer (rangifer tarandus tarandus) during early winter.

Science.gov (United States)

Miller, Andrea L; Evans, Alina L; Os, Øystein; Arnemo, Jon M

2013-04-01

Hematologic and serum biochemistry values were evaluated in free-ranging, wild Norwegian reindeer (Rangifer tarandus tarandus) as part of a reintroduction program in southwestern Norway in November 1995 and 1996. Animals were immobilized with medetomidine-ketamine by dart from a helicopter. Blood was drawn for serum chemistry from 31 adults (nine males and 22 females) and for hematology from 29 adults (eight males and 21 females). Significant differences (Ppaper provides the first report of baseline hematologic and serum biochemistry reference ranges for free-ranging, wild Norwegian reindeer during early winter.

Induction of cyclooxygenase-2 in macrophages by catalase: role of NF-kappaB and PI3K signaling pathways.

Science.gov (United States)

Jang, Byeong-Churl; Kim, Do-Hyun; Park, Jong-Wook; Kwon, Taeg Kyu; Kim, Sang-Pyo; Song, Dae-Kyu; Park, Jong-Gu; Bae, Jae-Hoon; Mun, Kyo-Chul; Baek, Won-Ki; Suh, Min-Ho; Hla, Timothy; Suh, Seong-Il

2004-04-02

Induction of COX-2 by catalase in smooth muscle cells, endothelial cells, and neuronal cells has been previously reported. However, the mechanism by which catalase up-regulates COX-2 remains poorly understood. In this study, we investigated the effect of catalase on induction of COX-2 in macrophages. The addition of catalase into Raw 264.7 macrophages induced COX-2 expression that was correlated with increased COX-2 transcription and mRNA stability. Catalase also induced activation of NF-kappaB, PI3K, ERKs, p38s, or JNKs. Catalase-induced COX-2 expression was abrogated by treatment of MG-132 (a NF-kappaB inhibitor) or LY294002 (a PI3K inhibitor), but not by treatment of PD98059 (an ERK inhibitor), SB203580 (a p38 inhibitor), or SP600125 (a JNK inhibitor). Moreover, inhibition of PI3K by LY294002 caused partial decrease of catalase-induced COX-2 transcription and steady-state COX-2 transcript levels, but not COX-2 mRNA stability. Together, these results suggest that catalase induces the expression of COX-2 in Raw 264.7 macrophages, and the induction is related with activation of NF-kappaB transcription factor and PI3K signaling pathway.

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: makram.essafi@pasteur.rns.tn [Laboratoire de Recherche sur la Transmission, le Controle et l' immunobiologie des Infections, Institut Pasteur de Tunis (Tunisia)

2012-02-03

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

IAPs contain an evolutionarily conserved ubiquitin-binding domain that regulates NF-kappaB as well as cell survival and oncogenesis

DEFF Research Database (Denmark)

Gyrd-Hansen, Mads; Darding, Maurice; Miasari, Maria

2008-01-01

found that the UBA domain is essential for the oncogenic potential of cIAP1, to maintain endothelial cell survival and to protect cells from TNF-alpha-induced apoptosis. Moreover, the UBA domain is required for XIAP and cIAP2-MALT1 to activate NF-kappaB. Our data suggest that the UBA domain of cIAP2......-MALT1 stimulates NF-kappaB signalling by binding to polyubiquitylated NEMO. Significantly, 98% of all cIAP2-MALT1 fusion proteins retain the UBA domain, suggesting that ubiquitin-binding contributes to the oncogenic potential of cIAP2-MALT1 in MALT lymphoma. Our data identify IAPs as ubiquitin...

International perception of lung sounds: a comparison of classification across some European borders.

Science.gov (United States)

Aviles-Solis, Juan Carlos; Vanbelle, Sophie; Halvorsen, Peder A; Francis, Nick; Cals, Jochen W L; Andreeva, Elena A; Marques, Alda; Piirilä, Päivi; Pasterkamp, Hans; Melbye, Hasse

2017-01-01

Lung auscultation is helpful in the diagnosis of lung and heart diseases; however, the diagnostic value of lung sounds may be questioned due to interobserver variation. This situation may also impair clinical research in this area to generate evidence-based knowledge about the role that chest auscultation has in a modern clinical setting. The recording and visual display of lung sounds is a method that is both repeatable and feasible to use in large samples, and the aim of this study was to evaluate interobserver agreement using this method. With a microphone in a stethoscope tube, we collected digital recordings of lung sounds from six sites on the chest surface in 20 subjects aged 40 years or older with and without lung and heart diseases. A total of 120 recordings and their spectrograms were independently classified by 28 observers from seven different countries. We employed absolute agreement and kappa coefficients to explore interobserver agreement in classifying crackles and wheezes within and between subgroups of four observers. When evaluating agreement on crackles (inspiratory or expiratory) in each subgroup, observers agreed on between 65% and 87% of the cases. Conger's kappa ranged from 0.20 to 0.58 and four out of seven groups reached a kappa of ≥0.49. In the classification of wheezes, we observed a probability of agreement between 69% and 99.6% and kappa values from 0.09 to 0.97. Four out of seven groups reached a kappa ≥0.62. The kappa values we observed in our study ranged widely but, when addressing its limitations, we find the method of recording and presenting lung sounds with spectrograms sufficient for both clinic and research. Standardisation of terminology across countries would improve international communication on lung auscultation findings.

Analysis of Hot Ions Detected during Equatorial Orbits of the Cassini Spacecraft at Saturn using the Convected Kappa Distribution Function and a Comparison to Voyager and Galileo Measurements at Jupiter

Science.gov (United States)

Kane, M.; Mitchell, D. G.; Carbary, J. F.; Hill, M. E.; Dialynas, K.; Mauk, B.; Krimigis, S. M.

2017-12-01

An extensive analysis of Cassini INCA and CHEMS measurements of 5-149 keV ions acquired during all equatorial orbits has been completed using a 3-D convected kappa distribution model. The computed plasma azimuthal speed, expressed as a fraction of the local corotation speed, decreases sharply with increasing distance from Saturn. The oxygen ion profile follows the hydrogen ion trend. For both species, the polar convection speed is the smallest of the 3 velocity components, and is centered about zero, but the radial speed has a significant radially outward component. Further, the radial component is enhanced in the pre-dawn sector. The hydrogen and oxygen temperatures increase with decreasing distance to Saturn. The calculated pattern of convection is consistent with an empirical model of plasma convection that includes outward radial transport and escape of plasma in a dawnside boundary layer of plasma entrained by the dawn magnetosheath flow. When the model convection pattern is scaled to the sub-solar magnetopause distance and to the sizes of Jupiter and Saturn, the pattern agrees with that derived from analysis of hot ions detected by the LECP detector on Voyager and the EPD instrument on Galileo. This and previous analysis of hot ion distributions has shown that the convected kappa distribution, with isotropy assumed in the plasma rest frame, has well described hot ion observed fluxes within a limited range of ion energies and has produced meaningful and ordered physical plasma parameters including plasma bulk velocity vectors, kappa distribution temperature profiles, and the general magnetospheric convection pattern at Jupiter and Saturn.

Electron density values of various human tissues: in vitro Compton scatter measurements and calculated ranges

International Nuclear Information System (INIS)

Shrimpton, P.C.

1981-01-01

Accurate direct measurements of electron density have been performed on specimens from 10 different tissue types of the human body, representing the major organs, using a Compton scatter technique. As a supplement to these experimental values, calculations have been carried out to determine the electron densities expected for these tissue types. The densities observed are in good agreement with the broad ranges deduced from the basic data previously published. The results of both the in vitro sample measurements and the approximate calculations indicate that the electron density of most normal healthy soft tissue can be expected to fall within the fairly restricted range of +- 5% around 3.4 X 10 23 electrons per cm 3 . The obvious exception to this generalisation is the result for lung tissue, which falls considerably below this range owing to the high air content inherent in its construction. In view of such an overall limited variation with little difference between tissues, it would appear that electron density alone is likely to be a rather poor clinical parameter for tissue analysis, with high accuracy and precision being essential in any in vivo Compton measurements for imaging or diagnosis on specific organs. (author)

Vitamin K3 attenuates lipopolysaccharide-induced acute lung injury through inhibition of nuclear factor-kappaB activation.

Science.gov (United States)

Tanaka, S; Nishiumi, S; Nishida, M; Mizushina, Y; Kobayashi, K; Masuda, A; Fujita, T; Morita, Y; Mizuno, S; Kutsumi, H; Azuma, T; Yoshida, M

2010-05-01

Vitamin K is a family of fat-soluble compounds including phylloquinone (vitamin K1), menaquinone (vitamin K2) and menadione (vitamin K3). Recently, it was reported that vitamin K, especially vitamins K1 and K2, exerts a variety of biological effects, and these compounds are expected to be candidates for therapeutic agents against various diseases. In this study, we investigated the anti-inflammatory effects of vitamin K3 in in vitro cultured cell experiments and in vivo animal experiments. In human embryonic kidney (HEK)293 cells, vitamin K3 inhibited the tumour necrosis factor (TNF)-alpha-evoked translocation of nuclear factor (NF)-kappaB into the nucleus, although vitamins K1 and K2 did not. Vitamin K3 also suppressed the lipopolysaccharide (LPS)-induced nuclear translocation of NF-kappaB and production of TNF-alpha in mouse macrophage RAW264.7 cells. Moreover, the addition of vitamin K3 before and after LPS administration attenuated the severity of lung injury in an animal model of acute lung injury/acute respiratory distress syndrome (ARDS), which occurs in the setting of acute severe illness complicated by systemic inflammation. In the ARDS model, vitamin K3 also suppressed the LPS-induced increase in the serum TNF-alpha level and inhibited the LPS-evoked nuclear translocation of NF-kappaB in lung tissue. Despite marked efforts, little therapeutic progress has been made, and the mortality rate of ARDS remains high. Vitamin K3 may be an effective therapeutic strategy against acute lung injury including ARDS.

HPLC assay for the determination of PD 117,302, a Kappa analgesic, and its application to disposition studies in rats

International Nuclear Information System (INIS)

Young, R.M.; Chang, T.

1986-01-01

PD 117,302-2 (I) trans-(+)-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl]benzo[b]thiophene-4-acetamide, monohydrochloride is a new Kappa analgesic. To facilitate preclinical development, an HPLC assay was developed. (I) and an internal standard were extracted from alkalinized rat plasma with CH 2 Cl 2 . HPLC was performed on a Waters Nova-Pak C 18 column (3.9 mm x 15 cm) using 0.5% triethylamine in 50:50 CH 3 CN/0.05M NH 4 H 2 PO 4 (pH 6.7) at a flow rate of 2 ml/min. UV absorbancy was monitored at 237 nm. Calibration curves were linear over a range of 80-4000 ng/ml. Within-day precision ranged 0.1-9.0% and between-day precision ranged 3.1-7.6%. 14 C-(I) given orally (10 mg/kg) was completely absorbed and extensively metabolized. Elimination t 1/2 of (I) averaged 2 hr. Fecal and urinary 14 C recoveries accounted for 54-76% and 9-12% of the dose, respectively. No intact drug was found in feces, indicating that the high fecal 14 C recovery was due to the presence of metabolites(s) rather than poor absorption

Phase transformation of the L12 phase to kappa-carbide after spinodal decomposition and ordering in an Fe–C–Mn–Al austenitic steel

International Nuclear Information System (INIS)

Cheng, Wei-Chun; Cheng, Chih-Yao; Hsu, Chia-Wei; Laughlin, David E.

2015-01-01

Fe–C–Mn–Al steels have the potential to substitute for commercial Ni–Cr stainless steels. For the development of Fe–C–Mn–Al stainless steels, phase transformations play an important role. Our methods of studying the phase transformations of the steel include heating, cooling, and/or annealing. The results of our study show that spinodal decomposition, an atomic ordering reaction and the transformation of the L1 2 phase to kappa-carbide occur in the Fe–C–Mn–Al steel. After cooling, the austenite decomposes by the spinodal mechanism into solute-lean and solute-rich austenite phases. The solute-rich austenite phase also transforms into the L1 2 phase via the ordering reaction upon cooling to lower temperatures. After quenching and prolonged annealing, the L1 2 phase grows in the austenite and finally transforms into kappa-carbide. This L1 2 phase to kappa-carbide transformation has not been observed previously

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

International Nuclear Information System (INIS)

Wu, Gang; Jin, Teng; Li, Ting; Li, Xiaoming

2016-01-01

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

Increased levels of NOTCH1, NF-kappaB, and other interconnected transcription factors characterize primitive sets of hematopoietic stem cells.

Science.gov (United States)

Panepucci, Rodrigo Alexandre; Oliveira, Lucila Habib B; Zanette, Dalila Luciola; Viu Carrara, Rita de Cassia; Araujo, Amélia Goes; Orellana, Maristela Delgado; Bonini de Palma, Patrícia Vianna; Menezes, Camila C B O; Covas, Dimas Tadeu; Zago, Marco Antonio

2010-03-01

As previously shown, higher levels of NOTCH1 and increased NF-kappaB signaling is a distinctive feature of the more primitive umbilical cord blood (UCB) CD34+ hematopoietic stem cells (HSCs), as compared to bone marrow (BM). Differences between BM and UCB cell composition also account for this finding. The CD133 marker defines a more primitive cell subset among CD34+ HSC with a proposed hemangioblast potential. To further evaluate the molecular basis related to the more primitive characteristics of UCB and CD133+ HSC, immunomagnetically purified human CD34+ and CD133+ cells from BM and UCB were used on gene expression microarrays studies. UCB CD34+ cells contained a significantly higher proportion of CD133+ cells than BM (70% and 40%, respectively). Cluster analysis showed that BM CD133+ cells grouped with the UCB cells (CD133+ and CD34+) rather than to BM CD34+ cells. Compared with CD34+ cells, CD133+ had a higher expression of many transcription factors (TFs). Promoter analysis on all these TF genes revealed a significantly higher frequency (than expected by chance) of NF-kappaB-binding sites (BS), including potentially novel NF-kappaB targets such as RUNX1, GATA3, and USF1. Selected transcripts of TF related to primitive hematopoiesis and self-renewal, such as RUNX1, GATA3, USF1, TAL1, HOXA9, HOXB4, NOTCH1, RELB, and NFKB2 were evaluated by real-time PCR and were all significantly positively correlated. Taken together, our data indicate the existence of an interconnected transcriptional network characterized by higher levels of NOTCH1, NF-kappaB, and other important TFs on more primitive HSC sets.

Agreement and reproducibility in identification of endometriosis using magnetic resonance imaging

International Nuclear Information System (INIS)

Saba, Luca; Sulcis, Rosa; Mallarini, Giorgio; Guerriero, Stefano; Ajossa, Silvia; Melis, Gianbenedetto

2010-01-01

Background: Magnetic resonance imaging (MRI) is a promising technique in the study of endometriosis, allowing a complete mapping of lesions before surgery. However, the value of MRI in the diagnosis of endometriosis in the bladder, in superficial peritoneal lesions, and in ovarian foci and uterosacral ligaments is still under debate. Purpose: To assess inter- and intra-observer agreement in the evaluation of endometriosis in different anatomical locations using MRI. Material and Methods: From June 2006 to February 2008, 83 female patients (mean age 39, range 19-49 years) who had undergone MRI examination for suspected endometriosis were evaluated by two radiologists. MRI at 1.5 Tesla was performed with SE and TSE sequences, T1- and T2-weighted with and without fat suppression. Each examination was completed with gadolinium administration. Each dataset was independently evaluated by the radiologists for the presence or absence of endometriosis. The location (ovaries, uterosacral ligaments (USLs), pouch of Douglas, vagina, rectosigmoid, rectovaginal septum, and bladder) of suspected lesions was recorded. Cohen kappa statistical analysis was performed to calculate agreement between measurements. After 2 months the data were analyzed again by the two observers to assess intra-observer agreement. Results: Of the 83 MRI examinations performed, 12 patients demonstrated no evidence of endometriosis. In the remaining 71 studies, 157 endometriotic lesions ranging in size from 0.4 to 6.2 cm were detected. Of the 157 lesions, 53 (33.75% incidence) were smaller than 1 cm. In the ovaries, the inter-observer agreement was 92.77% and the kappa value was 0.802 (95% CI, 0.695-0.91). In the bladder the inter-observer agreement was 96.39% and the kappa value was 0.553 (95% CI 0.056-1). In the USLs the inter-observer agreement was 90.96% and the kappa value 0.583 (95% CI, 0.381-0.784). In the rectovaginal septum the inter-observer agreement was 94.58% and the kappa value 0.739 (95% CI

Agreement and reproducibility in identification of endometriosis using magnetic resonance imaging

Energy Technology Data Exchange (ETDEWEB)

Saba, Luca; Sulcis, Rosa; Mallarini, Giorgio (Dept. of Science of the Images, Azienda Ospedaliero Universitaria di Cagliari, Cagliari (Italy)), e-mail: lucasaba@tiscali.it; Guerriero, Stefano; Ajossa, Silvia; Melis, Gianbenedetto (Dept. of Gynaecology, Azienda Ospedaliero Universitaria di Cagliari, Cagliari (Italy))

2010-06-15

Background: Magnetic resonance imaging (MRI) is a promising technique in the study of endometriosis, allowing a complete mapping of lesions before surgery. However, the value of MRI in the diagnosis of endometriosis in the bladder, in superficial peritoneal lesions, and in ovarian foci and uterosacral ligaments is still under debate. Purpose: To assess inter- and intra-observer agreement in the evaluation of endometriosis in different anatomical locations using MRI. Material and Methods: From June 2006 to February 2008, 83 female patients (mean age 39, range 19-49 years) who had undergone MRI examination for suspected endometriosis were evaluated by two radiologists. MRI at 1.5 Tesla was performed with SE and TSE sequences, T1- and T2-weighted with and without fat suppression. Each examination was completed with gadolinium administration. Each dataset was independently evaluated by the radiologists for the presence or absence of endometriosis. The location (ovaries, uterosacral ligaments (USLs), pouch of Douglas, vagina, rectosigmoid, rectovaginal septum, and bladder) of suspected lesions was recorded. Cohen kappa statistical analysis was performed to calculate agreement between measurements. After 2 months the data were analyzed again by the two observers to assess intra-observer agreement. Results: Of the 83 MRI examinations performed, 12 patients demonstrated no evidence of endometriosis. In the remaining 71 studies, 157 endometriotic lesions ranging in size from 0.4 to 6.2 cm were detected. Of the 157 lesions, 53 (33.75% incidence) were smaller than 1 cm. In the ovaries, the inter-observer agreement was 92.77% and the kappa value was 0.802 (95% CI, 0.695-0.91). In the bladder the inter-observer agreement was 96.39% and the kappa value was 0.553 (95% CI 0.056-1). In the USLs the inter-observer agreement was 90.96% and the kappa value 0.583 (95% CI, 0.381-0.784). In the rectovaginal septum the inter-observer agreement was 94.58% and the kappa value 0.739 (95% CI

Hypothalamic kappa opioid receptor mediates both diet- and MCH-induced liver damage through inflammation and ER stress

NARCIS (Netherlands)

Imbernon, Monica; Sanchez-Rebordelo, Estrella; Romero-Picó, Amparo; Kalló, Imre; Chee, Melissa J; Porteiro, Begoña; Al-Massadi, Omar; Contreras, Cristina; Fernø, Johan; Senra, Ana; Gallego, Rosalia; Folgueira, Cintia; Seoane, Luisa M; van Gestel, Margriet; Adan, Roger A; Liposits, Zsolt; Dieguez, Carlos; Lopez, Miguel; Nogueiras, Ruben

2016-01-01

The opioid system is widely known to modulate the brain reward system and thus affect human and animal behaviour, including feeding. We hypothesized that the hypothalamic opioid system might also control energy metabolism in peripheral tissues. Mice lacking the kappa opioid receptor (κOR) and

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

2008-01-01

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 ...

Distribution of mu, delta, and kappa opioid receptor binding sites in the brain of the one-day-old domestic chick (Gallus domesticus): An in vitro quantitative autoradiographic study

Energy Technology Data Exchange (ETDEWEB)

Csillag, A.; Bourne, R.C.; Stewart, M.G. (Open Univ., Milton Keynes (England))

1990-12-15

Three highly specific opioid ligands--(D-Ala2,Gly-ol)-enkephalin (DAGO) for mu (mu) receptor sites, (D-Pen2,D-Pen5)-enkephalin (DPDPE) for delta (delta) sites, and U-69593 for kappa (kappa) sites--were used to determine the regional distribution of the three major subtypes of opioid receptor binding sites in the brains of 1-day-old domestic chicks by the technique of quantitative receptor autoradiography. While there was a degree of heterogeneity in the binding levels of each of the ligands, some notable similarities existed in the binding of the mu and kappa ligands in several forebrain regions, and in the optic tectum of the midbrain where mu and delta binding was very high. In the forebrain there was a high level of binding of mu and kappa ligands in the hyperstriatum, and for the mu ligand there was a very distinct lamination of binding sites in hyperstriatum accessorium, intercalatum supremum, dorsale and ventrale. Levels of binding of the mu and kappa ligands were also high in nucleus basalis, and (for mu only) in the neostriatum. The distribution of binding of the delta specific ligand in the forebrain showed marked differences to that of mu and kappa, being particularly low in the hyperstriatum and neostriatum. Very high levels of labelling of delta binding sites were, however, found in the nucleus rotundus. Binding of the three ligands was generally low or absent in the cerebellum and medulla, apart from a distinct labelling of the granule cell layer by the mu-ligand. A kinetic analysis was made of the binding of the three ligands to whole forebrain sections using scintillation counting methods.

In-vivo performance of impedance spectroscopy, laser fluorescence, and bitewing radiographs for occlusal caries detection

DEFF Research Database (Denmark)

Mortensen, Diana; Hessing-Olsen, Ilse; Ekstrand, Kim Rud

2018-01-01

(DOR) using ICDAS as gold standard. Intra- and inter-examiner reproducibility was assessed with intra-class correlation coefficients (ICC) for numerical results and kappa values for categorical data. Five patients dropped out due to no-shows or restorative care. RESULTS: In total, 54% of the teeth had...... but low sensitivity, whereas LF-pen had moderate sensitivity and high specificity. Accuracy and DOR was highest for bitewing radiographs. The ICC values ranged between 0.65 and 0.88 for ACIS and 0.89 and 0.94 for LF-pen. The weighted kappa values were 0.81 to 0.91 for ICDAS and 0.90 to 0.92 for bitewing...

The changing relationship between HbA1c and FPG according to different FPG ranges.

Science.gov (United States)

Guan, X; Zheng, L; Sun, G; Guo, X; Li, Y; Song, H; Tian, F; Sun, Y

2016-05-01

Since the American Diabetes Association included hemoglobin A1c (HbA1c) in the diagnostic criteria for diabetes in 2010, the clinical use of HbA1c has remained controversial. We explored the use of HbA1c for diagnosing diabetes and intermediate hyperglycemia in comparison with fasting plasma glucose (FPG). We screened 3710 adult subjects (mean age = 55.24 years) comprising 1704 males and 2006 females. We drew an receiver operating characteristic (ROC) curve to evaluate the ability of HbA1c to diagnose diabetes and intermediate hyperglycemia according to FPG. We used Kappa coefficient and Pearson's correlation coefficient to evaluate the relationship between HbA1c and FPG in different FPG ranges. The areas under ROC curve to diagnose diabetes and intermediate hyperglycemia were 0.859 (95 % CI 0.827-0.892) and 0.633 (95 % CI 0.615-0.651). The kappa coefficients between FPG and HbA1c for diagnosis of diabetes and intermediate hyperglycemia were 0.601 (P HbA1c was 0.640 (P HbA1c and FPG changed according to the different FPG ranges. When FPG was higher, the relationship was stronger. HbA1c and FPG were highly consistent in diagnosing diabetes, but they were not in predicting intermediate hyperglycemia.

Felodipine attenuates vascular inflammation in a fructose-induced rat model of metabolic syndrome via the inhibition of NF-kappaB activation.

Science.gov (United States)

Tan, Hong-wei; Xing, Shan-shan; Bi, Xiu-ping; Li, Li; Gong, Hui-ping; Zhong, Ming; Zhang, Yun; Zhang, Wei

2008-09-01

Metabolic syndrome is associated with an increased incidence of atherosclerosis. Clinical studies have shown that calcium channel blockers (CCB) inhibit the progression of atherosclerosis. However, the underlying mechanism is unclear. We investigated the inhibitory effect of felodipine on adhesion molecular expression and macrophage infiltration in the aorta of high fructose-fed rats (FFR). Male Wistar rats were given 10% fructose in drinking water. After 32 weeks of high fructose feeding, they were treated with felodipine (5 mg x kg(-1) x d(-1)) for 6 weeks. The control rats were given a normal diet and water. The aortic expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and the infiltration of macrophages were measured by real-time RT-PCR and/or immunohistochemistry. NF-kappaB activity was measured by electrophoretic mobility shift assay (EMSA). After 32 weeks of high fructose feeding, FFR displayed increased body weight, systolic blood pressure (SBP), serum insulin, and triglycerides when compared with the control rats. The aortic expressions of ICAM-1 and VCAM-1 were significantly increased in FFR than in the control rats and accompanied by the increased activity of NF-kappaB. FFR also showed significantly increased CD68- positive macrophages in the aortic wall. After treatment with felodipine, SBP, serum insulin, and the homeostasis model assessment decreased significantly. In addition to reducing ICAM-1 and VCAM-1, felodipine decreased macrophages in the aortic wall. EMSA revealed that felodipine inhibited NF-kappaB activation in FFR. Felodipine inhibited vessel wall inflammation. The inhibition of NF-kappaB may be involved in the modulation of vascular inflammatory response by CCB in metabolic syndrome.

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

Science.gov (United States)

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

2014-01-01

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

The normally expressed kappa immunoglobulin light chain gene repertoire and somatic mutations studied by single-sided specific polymerase chain reaction (PCR); frequent occurrence of features often assigned to autoimmunity

DEFF Research Database (Denmark)

Juul, L; Hougs, L; Andersen, V

1997-01-01

The expressed human kappa light chain gene repertoire utilized by healthy individuals was studied by two different single-sided specific PCR techniques to avoid bias for certain V genes. A total of 103 rearranged kappa sequences from peripheral blood mononuclear cells from healthy individuals were...

Kappa opioid receptor antagonism and chronic antidepressant treatment have beneficial activities on social interactions and grooming deficits during heroin abstinence.

Science.gov (United States)

Lalanne, L; Ayranci, G; Filliol, D; Gavériaux-Ruff, C; Befort, K; Kieffer, B L; Lutz, P-E

2017-07-01

Addiction is a chronic brain disorder that progressively invades all aspects of personal life. Accordingly, addiction to opiates severely impairs interpersonal relationships, and the resulting social isolation strongly contributes to the severity and chronicity of the disease. Uncovering new therapeutic strategies that address this aspect of addiction is therefore of great clinical relevance. We recently established a mouse model of heroin addiction in which, following chronic heroin exposure, 'abstinent' mice progressively develop a strong and long-lasting social avoidance phenotype. Here, we explored and compared the efficacy of two pharmacological interventions in this mouse model. Because clinical studies indicate some efficacy of antidepressants on emotional dysfunction associated with addiction, we first used a chronic 4-week treatment with the serotonergic antidepressant fluoxetine, as a reference. In addition, considering prodepressant effects recently associated with kappa opioid receptor signaling, we also investigated the kappa opioid receptor antagonist norbinaltorphimine (norBNI). Finally, we assessed whether fluoxetine and norBNI could reverse abstinence-induced social avoidance after it has established. Altogether, our results show that two interspaced norBNI administrations are sufficient both to prevent and to reverse social impairment in heroin abstinent animals. Therefore, kappa opioid receptor antagonism may represent a useful approach to alleviate social dysfunction in addicted individuals. © 2016 Society for the Study of Addiction.

Rare and Common Variants in CARD14, Encoding an Epidermal Regulator of NF-kappaB, in Psoriasis

Science.gov (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.

2012-01-01

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

[Predictive value of qualitative assessment of general movements for adverse outcomes at 24 months of age in infants with asphyxia].

Science.gov (United States)

Chen, Nan; Wen, Xiao-Hong; Huang, Jin-Hua; Wang, Shui-Yun; Zhu, Yue-E

2015-12-01

To investigate the predictive value of the qualitative assessment of general movements (GMs) for adverse outcomes at 24 months of age in full-term infants with asphyxia. A total of 114 full-term asphyxiated infants, who were admitted to the neonatal intensive care unit between 2009 and 2012 and took part in follow-ups after discharge were included in the study. All of them received the qualitative assessment of GMs within 3 months after birth. The development quotient was determined with the Bayley Scales of Infant Development at 24 months of age. The results of the qualitative assessment of GMs within 3 months after birth showed that among 114 infants, 20 (17.5%) had poor repertoire movements and 7 (6.1%) had cramped-synchronized movements during the writhing movements period; 8 infants (7.0%) had the absence of fidgety movements during the fidgety movements period. The results of development quotient at 24 months of age showed that 7 infants (6.1%) had adverse developmental outcomes: 6 cases of cerebral palsy and mental retardation and 1 case of mental retardation. There was a poor consistency between poor repertoire movements during the writhing movements period and the developmental outcomes at 24 months of age (Kappa=-0.019; P>0.05). There was a high consistency between cramped-synchronized movements during the writhing movements period and the developmental outcomes at 24 months of age (Kappa=0.848; Ppredictive values of cramped-synchronized movements were shown as follows: predictive validity 98.2%, sensitivity 85.7%, specificity 99.1%, positive predictive value 85.7%, and negative predictive value 99.1%. There was a high consistency between the absence of fidgety movements during the fidgety movements period and the developmental outcomes at 24 months of age (Kappa=0.786; Ppredictive values were expressed as follows: predictive validity 97.4%, sensitivity 85.7%, specificity 98.1%, positive predictive value 75.0%, and negative predictive value 99.1%. Cramped

Exposure to chronic mild stress prevents kappa opioid-mediated reinstatement of cocaine and nicotine place preference

Directory of Open Access Journals (Sweden)

Ream eAl-Hasani

2013-08-01

Full Text Available Stress increases the risk of drug abuse, causes relapse to drug seeking, and potentiates the rewarding properties of both nicotine and cocaine. Understanding the mechanisms by which stress regulates the rewarding properties of drugs of abuse provides valuable insight into potential treatments for drug abuse. Prior reports have demonstrated that stress causes dynorphin release, activating kappa-opioid receptors (KOR in monoamine circuits resulting in both potentiation and reinstatement of cocaine and nicotine conditioned place preference. Here we report that kappa-opioid dependent reinstatement of cocaine and nicotine place preference is reduced when the mice are exposed to a randomized chronic mild stress regime prior to training in a conditioned place preference-reinstatement paradigm. The chronic mild stress schedule involves seven different stressors (removal of nesting for 24hr, 5min forced swim stress at 15°C, 8hr food and water deprivation, damp bedding overnight, white noise, cage tilt and disrupted home cage lighting rotated over a three-week period. This response is KOR-selective, because chronic mild stress does not protect against cocaine or nicotine drug-primed reinstatement. This protection from reinstatement is also observed following sub-chronic social defeat stress, where each mouse is placed in an aggressor mouse home cage for a period of 20 min over five days. In contrast, a single acute stressor resulted in a potentiation of KOR-induced reinstatement, similarly to previously reported. Prior studies have shown that stress alters sensitivity to opioids and prior stress can influence the pharmacodynamics of the opioid receptor system. Together, these findings suggest that exposure to different forms of stress may cause a dysregulation of kappa opioid circuitry and that changes resulting from mild stress can have protective and adaptive effects against drug relapse.

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

Science.gov (United States)

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

2018-02-01

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

Wide range neutron monitoring device

International Nuclear Information System (INIS)

Okido, Fumiyasu; Arita, Setsuo; Ishii, Kazuhiko; Matsumiya, Shoichi; Furusato, Ken-ichiro; Nishida, Akira.

1994-01-01

The present invention has a function of reliably switching measuring values between a pulse method and a Cambel method even if noise level and saturated level are fluctuated. That is, a proportional range judging means always monitors neutron flux measuring values in a start-up region and neutron flux measuring values in an intermediate power region, so that the proportional range is detected depending on whether the difference or a variation coefficient of both of the measured values is constant or not. A switching value determining means determines a switching value by the result of judgement of the proportional range judging means. A selection/output means selects and outputs measuring signals at a neutron flux level in the start-up region or the intermediate power region by the output of the switching value determining means. With such procedures, since the measuring value is switched after confirming that arrival at the proportional range where the difference or a variation coefficient of the measured value between the pulse processing method and the measured value by the Cambel method is constant, an accurate neutron flux level containing neither noise level nor saturated level can be outputted. (I.S.)

Nuclear Factor-kappaB in Autoimmunity: Man and Mouse.

Science.gov (United States)

Miraghazadeh, Bahar; Cook, Matthew C

2018-01-01

NF-κB (nuclear factor-kappa B) is a transcription complex crucial for host defense mediated by innate and adaptive immunity, where canonical NF-κB signaling, mediated by nuclear translocation of RelA, c-Rel, and p50, is important for immune cell activation, differentiation, and survival. Non-canonical signaling mediated by nuclear translocation of p52 and RelB contributes to lymphocyte maturation and survival and is also crucial for lymphoid organogenesis. We outline NF-κB signaling and regulation, then summarize important molecular contributions of NF-κB to mechanisms of self-tolerance. We relate these mechanisms to autoimmune phenotypes described in what is now a substantial catalog of immune defects conferred by mutations in NF-κB pathways in mouse models. Finally, we describe Mendelian autoimmune syndromes arising from human NF-κB mutations, and speculate on implications for understanding sporadic autoimmune disease.

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

Science.gov (United States)

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

2015-12-04

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

Association of Activation of Induced COX-2, iNOS and Cytokines with NF-kappa B Depression by Taiwan Wild Grape Ethanolic Extract in Mice.

Science.gov (United States)

Chang, Ching-Wen; Chen, Yi-Han; Lin, Yu-Chin; Peng, Wen-Huang

2017-08-31

Taiwan wild grape (Vitis thunbergii var. taiwaniana; VTT) is an important traditional herbal medicine used to treat muscle injuries and acute and chronic pain of the ligaments. Information on its bioactivity and the underlying mechanisms, which have not been elucidated thus far, is needed to demonstrate its value for pharmacological and clinical use. This study presents evidence to clarify the antinociceptive and anti-inflammatory activities of an ethanolic extract of VTT stem (VTTEtOH) and the possible molecular mechanisms involved in such biactivities. In the mice, VTTEtOH significantly reduced the acetic acid-induced writhing response (P < 0.01), formalin-induced licking time (P < 0.01), and edema paw volume at 4 and 5 h after λ-carrageenan injection. VTTEtOH obviously decreased the levels of tumor necrosis factor alpha (P < 0.01), interleukin (IL)-1β (P < 0.05), interleukin (IL)-6 (P < 0.001), nuclear factor-kappa B (P < 0.001), iNOS (P < 0.001), cyclooxygenase-2 (P < 0.001) and Nitric oxide (P < 0.001) in edema-paw tissue. The molecular mechanisms underlying these effects might involve significant inhibition of the activity of cyclooxygenase-2 through suppression of nuclear factor-kappa B and inducible nitric oxide synthase expression and reduction of the levels of various inflammatory mediators, including tumor necrosis factor alpha, interleukin (IL)-1β, IL-6, and nitric oxide. Our findings provided pharmacological and histopathological evidences that VTTEtOH alleviates inflammatory pain-related diseases.

Marginal instability threshold of magnetosonic waves in kappa distributed plasma

Science.gov (United States)

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

2017-12-01

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

Moderate extracellular acidification inhibits capsaicin-induced cell death through regulating calcium mobilization, NF-{kappa}B translocation and ROS production in synoviocytes

Energy Technology Data Exchange (ETDEWEB)

Hu, Fen; Yang, Shuang; Zhao, Dan; Zhu, Shuyan; Wang, Yuxiang [Department of Biophysics, School of Physics and Key Laboratory of Bioactive Materials of Education Ministry, Nankai University, Tianjin 300071 (China); Li, Junying, E-mail: jyli04@nankai.edu.cn [Department of Biophysics, School of Physics and Key Laboratory of Bioactive Materials of Education Ministry, Nankai University, Tianjin 300071 (China)

2012-07-20

Highlights: Black-Right-Pointing-Pointer Moderate extracellular acidification regulates intracellular Ca{sup 2+} mobilization. Black-Right-Pointing-Pointer Moderate acidification activates NF-{kappa}B nuclear translocation in synoviocytes. Black-Right-Pointing-Pointer Moderate acidification depresses the ROS production induced by capsaicin. Black-Right-Pointing-Pointer Moderate acidification inhibits capsaicin-caused synoviocyte death. -- Abstract: We previously show the expression of transient receptor potential vanilloid 1 (TRPV1) in primary synoviocytes from collagen-induced arthritis (CIA) rats. Capsaicin and lowered extracellular pH from 7.4 to 5.5 induce cell death through TRPV1-mediated Ca{sup 2+} entry and reactive oxygen species (ROS) production. However, under the pathological condition in rheumatoid arthritis, the synovial fluid is acidified to a moderate level (about pH 6.8). In the present study, we examined the effects of pH 6.8 on the TRPV1-mediated cell death. Our finding is different or even opposite from what was observed at pH 5.5. We found that the moderate extracellular acidification (from pH 7.4 to 6.8) inhibited the capsaicin-induced Ca{sup 2+} entry through attenuating the activity of TRPV1. In the mean time, it triggered a phospholipse C (PLC)-related Ca{sup 2+} release from intracellular stores. The nuclear translocation of NF-{kappa}B was found at pH 6.8, and this also depends on PLC activation. Moreover, the capsaicin-evoked massive ROS production and cell death were depressed at pH 6.8, both of which are dependent on the activation of PLC and NF-{kappa}B. Taken together, these results suggested that the moderate extracellular acidification inhibited the capsaicin-induced synoviocyte death through regulating Ca{sup 2+} mobilization, activating NF-{kappa}B nuclear translocation and depressing ROS production.

Inter-observer agreement in audit of quality of radiology requests and reports

International Nuclear Information System (INIS)

Stavem, K.; Foss, T.; Botnmark, O.; Andersen, O.K.; Erikssen, J.

2004-01-01

AIMS: To assess the quality of the imaging procedure requests and radiologists' reports using an auditing tool, and to assess the agreement between different observers of the quality parameters. MATERIALS AND METHODS: In an audit using a standardized scoring system, three observers reviewed request forms for 296 consecutive radiological examinations, and two observers reviewed a random sample of 150 of the corresponding radiologists' reports. We present descriptive statistics from the audit and pairwise inter-observer agreement, using the proportion agreement and kappa statistics. RESULTS: The proportion of acceptable item scores (0 or +1) was above 70% for all items except the requesting physician's bleep or extension number, legibility of the physician's name, or details about previous investigations. For pairs of observers, the inter-observer agreement was generally high, however, the corresponding kappa values were consistently low with only 14 of 90 ratings >0.60 and 6 >0.80 on the requests/reports. For the quality of the clinical information, the appropriateness of the request, and the requested priority/timing of the investigation items, the mean percentage agreement ranged 67-76, and the corresponding kappa values ranged 0.08-0.24. CONCLUSION: The inter-observer reliability of scores on the different items showed a high degree of agreement, although the kappa values were low, which is a well-known paradox. Current routines for requesting radiology examinations appeared satisfactory, although several problem areas were identified

Myelin activates FAK/Akt/NF-kappaB pathways and provokes CR3-dependent inflammatory response in murine system.

Directory of Open Access Journals (Sweden)

Xin Sun

2010-02-01

Full Text Available Inflammatory response following central nervous system (CNS injury contributes to progressive neuropathology and reduction in functional recovery. Axons are sensitive to mechanical injury and toxic inflammatory mediators, which may lead to demyelination. Although it is well documented that degenerated myelin triggers undesirable inflammatory responses in autoimmune diseases such as multiple sclerosis (MS and its animal model, experimental autoimmune encephalomyelitis (EAE, there has been very little study of the direct inflammatory consequences of damaged myelin in spinal cord injury (SCI, i.e., there is no direct evidence to show that myelin debris from injured spinal cord can trigger undesirable inflammation in vitro and in vivo. Our data showed that myelin can initiate inflammatory responses in vivo, which is complement receptor 3 (CR3-dependent via stimulating macrophages to express pro-inflammatory molecules and down-regulates expression of anti-inflammatory cytokines. Mechanism study revealed that myelin-increased cytokine expression is through activation of FAK/PI3K/Akt/NF-kappaB signaling pathways and CR3 contributes to myelin-induced PI3K/Akt/NF-kappaB activation and cytokine production. The myelin induced inflammatory response is myelin specific as sphingomyelin (the major lipid of myelin and myelin basic protein (MBP, one of the major proteins of myelin are not able to activate NF-kappaB signaling pathway. In conclusion, our results demonstrate a crucial role of myelin as an endogenous inflammatory stimulus that induces pro-inflammatory responses and suggest that blocking myelin-CR3 interaction and enhancing myelin debris clearance may be effective interventions for treating SCI.

Human xenospecific T suppressor cells inhibit T helper cell proliferation to porcine aortic endothelial cells, and NF-kappaB activity in porcine APC.

Science.gov (United States)

Ciubotariu, R; Li, J; Colovai, A I; Platt, J L; Cortesini, R; Suciu Foca Cortesini, N

2001-05-01

Human T suppressor cells (Ts), capable of preventing autologous T helper cells (Th) from reacting against xenogeneic pig endothelial cells and pig APC can be generated in vitro. Ts derive from a population of CD3(+)CD8(+)CD28(-) T lymphocytes and specifically recognize the MHC class I antigens of the APC used for in vitro immunization. To study the mechanism that underlies suppression, we investigated whether Ts inhibit the expression of costimulatory molecules in xenogeneic professional and semiprofessional APC. We found that Ts down-regulate Th-induced expression of CD86 in pig APC, and that this effect occurs at the level of transcription, as indicated by nuclear run-on and Northern blot assays. EMSA results revealed that inhibition of CD86 expression is mediated by inactivation of transcription factor NF-kappaB. Furthermore, transfection of pig APC with a vector expressing NF-kappaB p65 partially rescued Th-induced expression of the CD86 molecule. These results strongly support the concept that xenospecific Ts inhibit the APC function of xenogeneic cells by preventing activation of NF-kappaB.

Interrater reliability of the Volume-Viscosity Swallow Test; screening for dysphagia among hospitalized elderly medical patients.

Science.gov (United States)

Jørgensen, Lise Walther; Søndergaard, Kasper; Melgaard, Dorte; Warming, Susan

2017-12-01

Oropharyngeal dysphagia (OD) is prevalent among medical and geriatric patients admitted due to acute illness and it is associated with malnutrition, increased length of stay and increased mortality. A valid and reliable bedside screening test for patients at risk of OD is essential in order to detect patients in need of further assessment. The Volume-Viscosity Swallow Test (V-VST) has been shown to be a valid screening test for OD in mixed outpatient populations. However, as reliability of the test has yet to be investigated in a population of medical and geriatric patients admitted due to acute illness, we aimed to determine the interrater reliability of the V-VST in this clinical setting. Reporting in this study is in accordance with proposed guidelines for the reporting of reliability and agreement studies (GRRAS). In three Danish hospitals (CRD-BFH, CRD-GH, NDR-H) 11 skilled occupational therapists examined an unselected group of 110 patients admitted to geriatric or medical wards. In an overall agreement phase raters reached ≥80% agreement before data collection phase was commenced. The V-VST was applied to patients twice within maximum one hour by raters who administrated the test in an order based on randomization, blinded to each other's results. Agreement, Kappa values, weighed Kappa values and Kappa adjusted for bias and prevalence are reported. The interrater reliability of V-VST as screening test for OD in patients admitted to geriatric or medical wards was substantial with an overall Kappa value of 0.77 (95% CI 0.65-0.89) however interrater reliability varied among hospitals ranging from 0.37 (95% CI -0.01 to 0.41) to 0.85 (95% CI 0.75-1.00). Interrater reliability of the accompanying recommendations of volume and viscosity was moderate with a weighted kappa value of 0.55 (95% CI 0.37-0.73) for viscosity and 0.53 (95% CI 0.36-0.7) for volume. The overall prevalence of OD was 34.5%, ranging from 8% to 53.6% across hospitals. The prevalence and bias

INHIBITION OF THE DNA-BINDING ACTIVITY OF DROSOPHILA SUPPRESSOR OF HAIRLESS AND OF ITS HUMAN HOMOLOG, KBF2/RBP-J-KAPPA, BY DIRECT PROTEIN-PROTEIN INTERACTION WITH DROSOPHILA HAIRLESS

NARCIS (Netherlands)

BROU, C; LOGEAT, F; LECOURTOIS, M; VANDEKERCKHOVE, Joël; KOURILSKY, P; SCHWEISGUTH, F; ISRAEL, A

1994-01-01

We have purified the sequence-specific DNA-binding protein KBF2 and cloned the corresponding cDNA, which is derived from the previously described RBP-J kappa gene, the human homolog of the Drosophila Suppressor of Hairless [Su(H)] gene. Deletion studies of the RBP-J kappa and Su(H) proteins allowed

Acrolein inhibits cytokine gene expression by alkylating cysteine and arginine residues in the NF-kappaB1 DNA binding domain.

Science.gov (United States)

Lambert, Cherie; Li, Jimei; Jonscher, Karen; Yang, Teng-Chieh; Reigan, Philip; Quintana, Megan; Harvey, Jean; Freed, Brian M

2007-07-06

Cigarette smoke is a potent inhibitor of pulmonary T cell responses, resulting in decreased immune surveillance and an increased incidence of respiratory tract infections. The alpha,beta-unsaturated aldehydes in cigarette smoke (acrolein and crotonaldehyde) inhibited production of interleukin-2 (IL-2), IL-10, granulocyte-macrophage colony-stimulating factor, interferon-gamma, and tumor necrosis factor-alpha by human T cells but did not inhibit production of IL-8. The saturated aldehydes (acetaldehyde, propionaldehyde, and butyraldehyde) in cigarette smoke were inactive. Acrolein inhibited induction of NF-kappaB DNA binding activity after mitogenic stimulation of T cells but had no effect on induction of NFAT or AP-1. Acrolein inhibited NF-kappaB1 (p50) binding to the IL-2 promoter in a chromatin immunoprecipitation assay by >99%. Using purified recombinant p50 in an electrophoretic mobility shift assay, we demonstrated that acrolein was 2000-fold more potent than crotonaldehyde in blocking DNA binding to an NF-kappaB consensus sequence. Matrix-assisted laser desorption/ionization time-of-flight and tandem mass spectrometry demonstrated that acrolein alkylated two amino acids (Cys-61 and Arg-307) in the DNA binding domain. Crotonaldehyde reacted with Cys-61, but not Arg-307, whereas the saturated aldehydes in cigarette smoke did not react with p50. These experiments demonstrate that aldehydes in cigarette smoke can regulate gene expression by direct modification of a transcription factor.

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

Science.gov (United States)

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

2017-01-01

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

Standard formation enthalpies of Nasub(2+x)Vsub(6)Osub(16-y) bronze of kappa type

International Nuclear Information System (INIS)

Khodos, M.Ya.; Slobodin, B.V.; Surat, L.L.; Fotiev, A.A.

1980-01-01

Standard formation enthalpies of sodium oxide vanadium bronze of kappa Nasub(2+x)Vsub(6)Osub(16-y) type of different composition have been determined by the method of solution calorimetry. It has been ascertained that within the limits of homogeneity a standard formation enthalpy decreases insignificantly with the increase of bronze oxygen defectiveness and is a linear function of sodium content

Diagnostic performance of MR imaging findings and quantitative values in the differentiation of seromucinous borderline tumour from endometriosis-related malignant ovarian tumour

Energy Technology Data Exchange (ETDEWEB)

Kurata, Yasuhisa; Kido, Aki; Moribata, Yusaku; Kameyama, Kyoko; Himoto, Yuki; Togashi, Kaori [Kyoto University Graduate School of Medicine, Department of Diagnostic Imaging and Nuclear Medicine, 54 Kawahara-cho, Shogoin, Sakyoku, Kyoto (Japan); Minamiguchi, Sachiko [Kyoto University Graduate School of Medicine, Department of Diagnostic Pathology, 54 Kawahara-cho, Shogoin, Sakyoku, Kyoto (Japan); Konishi, Ikuo [Kyoto University Graduate School of Medicine, Department of Gynecology and Obstetrics, 54 Kawahara-cho, Shogoin, Sakyoku, Kyoto (Japan)

2017-04-15

To evaluate the diagnostic performance of quantitative values and MRI findings for differentiating seromucinous borderline tumours (SMBTs) from endometriosis-related malignant ovarian tumours (MT). This retrospective study examined 19 lesions from SMBT and 84 lesions from MT. The following quantitative values were evaluated using receiver-operating characteristic analysis: overall and solid portion sizes, fluid signal intensity (SI), degree of contrast-enhancement, and mean and minimum apparent diffusion coefficient (ADC) values of the solid portion. Two radiologists independently evaluated four MRI findings characteristic of SMBT, fluid SI on the T1-weighted image and SI of the solid portion on diffusion-weighted image. The diagnostic values of these findings and interobserver agreement were assessed. For diagnosing SMBT, the mean ADC value of the solid portion showed the greatest area under the curve (0.860) (cut-off value: 1.31 x 10{sup -3} mm{sup 2}/s, sensitivity: 1.00, specificity: 0.61). The T2-weighted image (T2WI) high SI solid portion was the most useful finding, with high specificity and interobserver agreement (sensitivity, 0.58; specificity, 0.95-0.96, kappa = 0.96), followed by T2WI low SI core (sensitivity, 0.48-0.63; specificity, 0.98, kappa = 0.68). Mean ADC values of the solid portion, T2WI high SI solid portion, and T2WI low SI core were useful for differentiating SMBT from MT. (orig.)

Distribution of kappa and lambda light chain isotypes among human blood immunoglobulin-secreting cells after vaccination with pneumococcal polysaccharides

DEFF Research Database (Denmark)

Heilmann, C; Barington, T

1989-01-01

The light chain isotype of immunoglobulin-secreting blood cells was investigated by means of monolayer plaque-forming cell assays allowing direct immunofluorescence staining for cytoplasmic kappa and lambda light chains in centre cells. The study revealed that cultured, polyclonally activated...

The value of diffusion-weighted imaging in combination with T2-weighted imaging for rectal cancer detection

International Nuclear Information System (INIS)

Rao Shengxiang; Zeng Mengsu; Chen Caizhong; Li Renchen; Zhang Shujie; Xu Jianming; Hou Yingyong

2008-01-01

Objective: To evaluate the clinical value of diffusion-weighted imaging (DWI) in combination with T 2 -weighted imaging (T 2 WI) for the detection of rectal cancer as compared with T 2 WI alone. Materials and methods: Forty-five patients with rectal cancer and 20 without rectal cancer underwent DWI with parallel imaging and T 2 WI on a 1.5 T scanner. Images were independently reviewed by two readers blinded to the results to determine the detectability of rectal cancer. The detectability of T 2 W imaging without and with DW imaging was assessed by means of receiver operating characteristic analysis. The interobserver agreement between the two readers was calculated with kappa statistics. Results: The ROC analysis showed that each of two readers achieved more accurate results with T 2 W imaging combined with DW imaging than with T 2 W imaging alone significantly. The A z values for the two readers for each T 2 WI and T 2 WI combined with DWI were 0.918 versus 0.991 (p = 0.0494), 0.934 versus 0.997 (p = 0.0475), respectively. The values of kappa were 0.934 for T 2 WI and 0.948 for T 2 WI combined with DWI between the two readers. Conclusion: The addition of DW imaging to conventional T 2 W imaging provides better detection of rectal cancer

IgG,kappa monoclonal gammopathy of unknown significance with AL amyloidosis simulating giant cell arteritis

Directory of Open Access Journals (Sweden)

Pompilian Valer Mihai

2017-09-01

Full Text Available Monoclonal gammopathies complicated by AL amyloidosis can mimic giant cell arteritis (GCA. We hereby present the case of a 63 year old woman in whom symptoms consistent with GCA were the first manifestations of a monoclonal gammopathy of unknown significance (MGUS associated with amyloidosis. A 63 year old woman was admitted for temporal headache, maseterine claudication, neck and shoulder stiffness. She was recently diagnosed with carpal tunnel syndrome. On physical examination she had prominent temporal arteries, macroglosia and orthostatic hypotension. Muscular strength was normal. She had high ESR and CRP; in this clinical context, GCA was suspected. A gamma spike on serum protein electrophoresis raised the suspicion of monoclonal gammopathy (MG. Immunoelectrophoresis revealed monoclonal bands for IgG and kappa chains. Massive deposits of amyloid and no inflammation were found on temporal artery biopsy. Multiple myeloma and lymphoma were ruled out. A diagnosis of AL amyloidosis complicating MGUS was formulated. She did well on therapy with bortezomib, cyclophosphamide and dexamethasone. Cases published in medical literature reveal amyloidosis mimicking GCA in the setting of established MGUS. As far as we know, this is the first case of MGUS with IgG and kappa chains in which a GCA-like picture induced by amyloidosis was present from the very onset.

Phase transformation of the L1{sub 2} phase to kappa-carbide after spinodal decomposition and ordering in an Fe–C–Mn–Al austenitic steel

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Cheng, Wei-Chun, E-mail: weicheng@mail.ntust.edu.tw [Department of Mechanical Engineering, National Taiwan University of Science and Technology, 43 Keelung Road, Section 4, Taipei 106, Taiwan (China); Cheng, Chih-Yao; Hsu, Chia-Wei [Department of Mechanical Engineering, National Taiwan University of Science and Technology, 43 Keelung Road, Section 4, Taipei 106, Taiwan (China); Laughlin, David E. [Department of Materials Science and Engineering, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA (United States)

2015-08-26

Fe–C–Mn–Al steels have the potential to substitute for commercial Ni–Cr stainless steels. For the development of Fe–C–Mn–Al stainless steels, phase transformations play an important role. Our methods of studying the phase transformations of the steel include heating, cooling, and/or annealing. The results of our study show that spinodal decomposition, an atomic ordering reaction and the transformation of the L1{sub 2} phase to kappa-carbide occur in the Fe–C–Mn–Al steel. After cooling, the austenite decomposes by the spinodal mechanism into solute-lean and solute-rich austenite phases. The solute-rich austenite phase also transforms into the L1{sub 2} phase via the ordering reaction upon cooling to lower temperatures. After quenching and prolonged annealing, the L1{sub 2} phase grows in the austenite and finally transforms into kappa-carbide. This L1{sub 2} phase to kappa-carbide transformation has not been observed previously.

Kappa opioid receptors in rat spinal cord vary across the estrous cycle.

Science.gov (United States)

Chang, P C; Aicher, S A; Drake, C T

2000-04-07

Kappa opioid receptors (KORs) were immunocytochemically localized in the lumbosacral spinal cord of female rats in different stages of the estrous cycle to examine the influence of hormonal status on receptor density. KOR labeling was primarily in fine processes and a few neuronal cell bodies in the superficial dorsal horn and the dorsolateral funiculus. Quantitative light microscopic densitometry of the superficial dorsal horn revealed that rats in diestrus had significantly lower KOR densities than those in proestrus or estrus. This suggests that female reproductive hormones regulate spinal KOR levels, which may contribute to variations in analgesic effectiveness of KOR agonists across the estrous cycle.

Oligo-carrageenan kappa-induced reducing redox status and activation of TRR/TRX system increase the level of indole-3-acetic acid, gibberellin A3 and trans-zeatin in Eucalyptus globulus trees.

Science.gov (United States)

González, Alberto; Contreras, Rodrigo A; Zúiga, Gustavo; Moenne, Alejandra

2014-08-20

Eucalyptus globulus trees treated with oligo-carrageenan (OC) kappa showed an increase in NADPH, ascorbate and glutathione levels and activation of the thioredoxin reductase (TRR)/thioredoxin (TRX) system which enhance photosynthesis, basal metabolism and growth. In order to analyze whether the reducing redox status and the activation of thioredoxin reductase (TRR)/thioredoxin (TRX) increased the level of growth-promoting hormones, trees were treated with water (control), with OC kappa, or with inhibitors of ascorbate synthesis, lycorine, glutathione synthesis, buthionine sulfoximine (BSO), NADPH synthesis, CHS-828, and thioredoxin reductase activity, auranofine, and with OC kappa, and cultivated for four additional months. Eucalyptus trees treated with OC kappa showed an increase in the levels of the auxin indole 3-acetic acid (IAA), gibberellin A3 (GA3) and the cytokinin trans-zeatin (t-Z) as well as a decrease in the level of the brassinosteroid epi-brassinolide (EB). In addition, treatment with lycorine, BSO, CHS-828 and auranofine inhibited the increase in IAA, GA3 and t-Z as well as the decrease in EB levels. Thus, the reducing redox status and the activation of TRR/TRX system induced by OC kappa increased the levels of IAA, GA3 and t-Z levels determining, at least in part, the stimulation of growth in Eucalyptus trees.

Does the Lever Sign Test Have Added Value for Diagnosing Anterior Cruciate Ligament Ruptures?

Science.gov (United States)

Lichtenberg, Miranda C.; Koster, Christiaan H.; Teunissen, Lennart P.J.; Oosterveld, Frits G.J.; Harmsen, Annelieke M.K.; Haverkamp, Daniel; Hoornenborg, Daniel; Berg, Robert P.; Bloemers, Frank W.; Faber, Irene R.

2018-01-01

Background: Diagnosing an anterior cruciate ligament (ACL) rupture based on a physical examination remains a challenge for both surgeons and physical therapists. The lever sign test was developed to overcome the practical limitations of other tests and to optimize diagnosis. An evaluation of the measurement properties of the lever sign test is needed to make adequate interpretations in practice. Purpose: To evaluate the reliability and diagnostic value of the lever sign test. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: A total of 94 patients were recruited between November 2014 and July 2016. Patients were included if they were at least 16 years old, suffered from knee trauma, and had indications for knee arthroscopic surgery. Lever sign, anterior drawer, Lachman, and pivot-shift test outcomes were examined by an orthopaedic/trauma surgeon and a physical therapist. A test-retest design was used to investigate interrater reliability. Moreover, the lever sign test outcomes, alone and in combination with the other diagnostic tests, were compared with arthroscopic results, which served as the gold standard for the test’s diagnostic value. Results: The lever sign test and pivot-shift test had kappa values exceeding 0.80 for interrater reliability. The kappa values for the anterior drawer test and Lachman test were 0.80 and 0.77, respectively. The lever sign test showed the highest specificity (100%) and the lowest sensitivity (39%) when compared with the other 3 tests. Moreover, its positive and negative predictive values were 100% and 65%, respectively, while an accuracy of 71% was calculated. Clustering the lever sign test parallel with the other 3 tests resulted in the highest accuracy of 91%. Conclusion: The lever sign test appears to have high interrater reliability and is the most specific test, showing a maximal positive predictive value. A positive lever sign test result indicates an ACL rupture. These results support the added value

Generation of a KOR-Cre knockin mouse strain to study cells involved in kappa opioid signaling.

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Cai, Xiaoyun; Huang, Huizhen; Kuzirian, Marissa S; Snyder, Lindsey M; Matsushita, Megumi; Lee, Michael C; Ferguson, Carolyn; Homanics, Gregg E; Barth, Alison L; Ross, Sarah E

2016-01-01

The kappa opioid receptor (KOR) has numerous important roles in the nervous system including the modulation of mood, reward, pain, and itch. In addition, KOR is expressed in many non-neuronal tissues. However, the specific cell types that express KOR are poorly characterized. Here, we report the development of a KOR-Cre knockin allele, which provides genetic access to cells that express KOR. In this mouse, Cre recombinase (Cre) replaces the initial coding sequence of the Opkr1 gene (encoding the kappa opioid receptor). We demonstrate that the KOR-Cre allele mediates recombination by embryonic day 14.5 (E14.5). Within the brain, KOR-Cre shows expression in numerous areas including the cerebral cortex, nucleus accumbens and striatum. In addition, this allele is expressed in epithelium and throughout many regions of the body including the heart, lung, and liver. Finally, we reveal that KOR-Cre mediates recombination of a subset of bipolar and amacrine cells in the retina. Thus, the KOR-Cre mouse line is a valuable new tool for conditional gene manipulation to enable the study of KOR. © 2015 Wiley Periodicals, Inc.

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

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Rakić Mia

2013-01-01

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.

Kappa statistic for the clustered dichotomous responses from physicians and patients

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

2013-01-01

The bootstrap method for estimating the standard error of the kappa statistic in the presence of clustered data is evaluated. Such data arise, for example, in assessing agreement between physicians and their patients regarding their understanding of the physician-patient interaction and discussions. We propose a computationally efficient procedure for generating correlated dichotomous responses for physicians and assigned patients for simulation studies. The simulation result demonstrates that the proposed bootstrap method produces better estimate of the standard error and better coverage performance compared to the asymptotic standard error estimate that ignores dependence among patients within physicians with at least a moderately large number of clusters. An example of an application to a coronary heart disease prevention study is presented. PMID:23533082

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

2015-01-01

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 a...... of novel benzimidazole derivatives as KOR agonists are described. The in vivo proof of principle for anti-nociceptive effect with a lead compound from this series is exemplified....

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

2011-01-01

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 occlus...

CAPERalpha is a novel Rel-TAD-interacting factor that inhibits lymphocyte transformation by the potent Rel/NF-kappaB oncoprotein v-Rel.

Science.gov (United States)

Dutta, Jui; Fan, Gaofeng; Gélinas, Céline

2008-11-01

The Rel/NF-kappaB transcription factors are constitutively activated in many human cancers. The Rel proteins in this family are implicated in leukemia/lymphomagenesis, but the mechanism is not completely understood. Previous studies showed that the transcription activation domains (TADs) of the viral oncoprotein v-Rel and its cellular Rel/NF-kappaB homologues c-Rel and RelA are key determinants of their different transforming activities in primary lymphocytes. Substitution of a Rel TAD for that of RelA conferred a strong transforming phenotype upon RelA, which otherwise failed to transform cells. To gain insights into protein interactions that influence cell transformation by the Rel TADs, we identified factors that interact with the TAD of v-Rel, the most oncogenic member of the Rel/NF-kappaB family. We report that the coactivator for transcription factors AP-1 and estrogen receptors, CAPERalpha, interacts with the v-Rel TAD and potently synergizes v-Rel-mediated transactivation. Importantly, coexpression of CAPERalpha markedly reduced and delayed v-Rel's transforming activity in primary lymphocytes, whereas a dominant-negative mutant enhanced the kinetics of v-Rel-mediated transformation. Furthermore, small interfering RNA-mediated knockdown of CAPERalpha in v-Rel-transformed lymphocytes significantly enhanced colony formation in soft agar. Since the potency of Rel-mediated transactivation is an important determinant of lymphocyte transformation, as is Rel's ability to induce transcriptional repression, these data suggest that CAPERalpha's interaction with the Rel TAD could modulate Rel/NF-kappaB's transforming activity by facilitating expression or dampening repression of specific gene subsets important for oncogenesis. Overall, this study identifies CAPERalpha as a new transcriptional coregulator for v-Rel and reveals an important role in modulating Rel's oncogenic activity.

The 39th Annual Phi Delta Kappa/Gallup Poll of the Public's Attitudes toward the Public Schools

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Rose, Lowell C.; Gallup, Alec M.

2007-01-01

In this article, the authors report the results of the 39th Annual Phi Delta Kappa/Gallup Poll of the public's attitudes toward the public schools. This year's report examined the public's assessment of the No Child Left Behind (NCLB) and its principal strategy, standardized testing. The authors include a summary of key findings and tables showing…

Prognostic Value of Serum Free Light Chain in Multiple Myeloma.

Science.gov (United States)

El Naggar, Amel A; El-Naggar, Mostafa; Mokhamer, El-Hassan; Avad, Mona W

2015-01-01

The measurement of serum free light chain (sFLC) has been shown to be valuable in screening for the presence of plasma cell dyscrasia as well as for baseline prognosis in newly diagnosed patients. The aim of the present work was to study the prognostic value of sFLC in multiple myeloma in relation to other serum biomarkers, response to therapy and survival. Forty five newly diagnosed patients with MM were included in the study. Patients were divided into responders and non-responders groups according to response to therapy. sFLC and serum Amyloid A (SAA) were measured by immunonephelometry. The non-responders group showed a statistically significant higher kappa/lambda or lambda/kappa ratio and higher β2 microglobulin level, but lower albumin level at presentation, as compared to the responders group (P < 0.001). However, no statistically significant difference was detected between the two groups regarding SA A or calcium levels. Comparison between sFLC ratio obtained before and after therapy revealed significant decrease after treatment in the responders group (P = 0.05). Survival was significantly inferior in patients with an FLC ratio of ≥ 2.6 or ≤ 0.56 compared with those with an FLC ratio that was between 0.56 and 2.6 (P = 0.002).

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.

Science.gov (United States)

Liu, Yunbao; Yadev, Vivek R; Aggarwal, Bharat B; Nair, Muraleedharan G

2010-08-01

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.

Targeted adenovirus mediated inhibition of NF-kappa B-dependent inflammatory gene expression in endothelial cells in vitro and in vivo

NARCIS (Netherlands)

Kuldo, J. M.; Asgeirsdottir, S. A.; Zwiers, P. J.; Bellu, A. R.; Rots, M. G.; Schalk, J. A. C.; Ogawara, K. I.; Trautwein, C.; Banas, B.; Haisma, H. J.; Molema, G.; Kamps, J. A. A. M.

2013-01-01

In chronic inflammatory diseases the endothelium expresses mediators responsible for harmful leukocyte infiltration. We investigated whether targeted delivery of a therapeutic transgene that inhibits nuclear factor kappa B signal transduction could silence the proinflammatory activation status of

Comparative study between the hand-wrist method and cervical vertebral maturation method for evaluation skeletal maturity in cleft patients.

Science.gov (United States)

Manosudprasit, Montian; Wangsrimongkol, Tasanee; Pisek, Poonsak; Chantaramungkorn, Melissa

2013-09-01

To test the measure of agreement between use of the Skeletal Maturation Index (SMI) method of Fishman using hand-wrist radiographs and the Cervical Vertebral Maturation Index (CVMI) method for assessing skeletal maturity of the cleft patients. Hand-wrist and lateral cephalometric radiographs of 60 cleft subjects (35 females and 25 males, age range: 7-16 years) were used. Skeletal age was assessed using an adjustment to the SMI method of Fishman to compare with the CVMI method of Hassel and Farman. Agreement between skeletal age assessed by both methods and the intra- and inter-examiner reliability of both methods were tested by weighted kappa analysis. There was good agreement between the two methods with a kappa value of 0.80 (95% CI = 0.66-0.88, p-value <0.001). Reliability of intra- and inter-examiner of both methods was very good with kappa value ranging from 0.91 to 0.99. The CVMI method can be used as an alternative to the SMI method in skeletal age assessment in cleft patients with the benefit of no need of an additional radiograph and avoiding extra-radiation exposure. Comparing the two methods, the present study found better agreement from peak of adolescence onwards.

HEVC for high dynamic range services

Science.gov (United States)

Kim, Seung-Hwan; Zhao, Jie; Misra, Kiran; Segall, Andrew

2015-09-01

Displays capable of showing a greater range of luminance values can render content containing high dynamic range information in a way such that the viewers have a more immersive experience. This paper introduces the design aspects of a high dynamic range (HDR) system, and examines the performance of the HDR processing chain in terms of compression efficiency. Specifically it examines the relation between recently introduced Society of Motion Picture and Television Engineers (SMPTE) ST 2084 transfer function and the High Efficiency Video Coding (HEVC) standard. SMPTE ST 2084 is designed to cover the full range of an HDR signal from 0 to 10,000 nits, however in many situations the valid signal range of actual video might be smaller than SMPTE ST 2084 supported range. The above restricted signal range results in restricted range of code values for input video data and adversely impacts compression efficiency. In this paper, we propose a code value remapping method that extends the restricted range code values into the full range code values so that the existing standards such as HEVC may better compress the video content. The paper also identifies related non-normative encoder-only changes that are required for remapping method for a fair comparison with anchor. Results are presented comparing the efficiency of the current approach versus the proposed remapping method for HM-16.2.

Evaluation of different mathematical models and different b-value ranges of diffusion-weighted imaging in peripheral zone prostate cancer detection using b-value up to 4500 s/mm2.

Directory of Open Access Journals (Sweden)

Zhaoyan Feng

Full Text Available To evaluate the diagnostic performance of different mathematical models and different b-value ranges of diffusion-weighted imaging (DWI in peripheral zone prostate cancer (PZ PCa detection.Fifty-six patients with histologically proven PZ PCa who underwent DWI-magnetic resonance imaging (MRI using 21 b-values (0-4500 s/mm2 were included. The mean signal intensities of the regions of interest (ROIs placed in benign PZs and cancerous tissues on DWI images were fitted using mono-exponential, bi-exponential, stretched-exponential, and kurtosis models. The b-values were divided into four ranges: 0-1000, 0-2000, 0-3200, and 0-4500 s/mm2, grouped as A, B, C, and D, respectively. ADC, , D*, f, DDC, α, Dapp, and Kapp were estimated for each group. The adjusted coefficient of determination (R2 was calculated to measure goodness-of-fit. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic performance of the parameters.All parameters except D* showed significant differences between cancerous tissues and benign PZs in each group. The area under the curve values (AUCs of ADC were comparable in groups C and D (p = 0.980 and were significantly higher than those in groups A and B (p< 0.05 for all. The AUCs of ADC and Kapp in groups B and C were similar (p = 0.07 and p = 0.954, and were significantly higher than the other parameters (p< 0.001 for all. The AUCs of ADC in group D was slightly higher than Kapp (p = 0.002, and both were significantly higher than the other parameters (p< 0.001 for all.ADC derived from conventional mono-exponential high b-value (3200 s/mm2 models is an optimal parameter for PZ PCa detection.

Cellular and molecular mechanisms of chronic rhinosinusitis and potential therapeutic strategies: review on cytokines, nuclear factor kappa B and transforming growth factor beta.

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Phan, N T; Cabot, P J; Wallwork, B D; Cervin, A U; Panizza, B J

2015-07-01

Chronic rhinosinusitis is characterised by persistent inflammation of the sinonasal mucosa. Multiple pathophysiological mechanisms are likely to exist. Previous research has focused predominantly on T-helper type cytokines to highlight the inflammatory mechanisms. However, proteins such as nuclear factor kappa B and transforming growth factor beta are increasingly recognised to have important roles in sinonasal inflammation and tissue remodelling. This review article explores the roles of T-helper type cytokines, nuclear factor kappa B and transforming growth factor beta in the pathophysiological mechanisms of chronic rhinosinusitis. An understanding of these mechanisms will allow for better identification and classification of chronic rhinosinusitis endotypes, and, ultimately, improved therapeutic strategies.

TGF-{beta}1 increases invasiveness of SW1990 cells through Rac1/ROS/NF-{kappa}B/IL-6/MMP-2

Energy Technology Data Exchange (ETDEWEB)

Binker, Marcelo G. [Departments of Medicine and Physiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8 (Canada); CBRHC Research Center, Buenos Aires (Argentina); Binker-Cosen, Andres A. [CBRHC Research Center, Buenos Aires (Argentina); Gaisano, Herbert Y. [Departments of Medicine and Physiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8 (Canada); Cosen, Rodica H. de [CBRHC Research Center, Buenos Aires (Argentina); Cosen-Binker, Laura I., E-mail: laura.cosen.binker@utoronto.ca [Departments of Medicine and Physiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8 (Canada); CBRHC Research Center, Buenos Aires (Argentina)

2011-02-04

Research highlights: {yields} Rac1 mediates TGF-{beta}1-induced SW1990 invasion through MMP-2 secretion and activation. {yields} NADPH-generated ROS act downstream of Rac1 in TGF-{beta}1-challenged SW1990 cells. {yields} TGF-{beta}1-stimulated ROS activate NF-{kappa}B in SW1990 cells. {yields} NF{kappa}B-induced IL-6 release is required for secretion and activation of MMP-2 in SW1990 cells. -- Abstract: Human pancreatic cancer invasion and metastasis have been found to correlate with increased levels of active matrix metalloproteinase 2 (MMP-2). The multifunctional cytokine transforming growth factor beta 1 (TGF-{beta}1) has been shown to increase both secretion of MMP-2 and invasion by several pancreatic cancer cell types. In the present study, we investigated the signaling pathway involved in TGF-{beta}1-promoted MMP-2 secretion and invasion by human pancreatic cancer cells SW1990. Using specific inhibitors, we found that stimulation of these tumor cells with TGF-{beta}1 induced secretion and activation of the collagenase MMP-2, which was required for TGF-{beta}1-stimulated invasion. Our results also indicate that signaling events involved in TGF-{beta}1-enhanced SW1990 invasiveness comprehend activation of Rac1 followed by generation of reactive oxygen species through nicotinamide adenine dinucleotide phosphate-oxidase, activation of nuclear factor-kappa beta, release of interleukin-6, and secretion and activation of MMP-2.

"Give It Your Best Shot!": Address to Columbia College Students Elected to the Phi Beta Kappa Society

Science.gov (United States)

Kroeber, Karl

2012-01-01

This article presents the address delivered by the author to Columbia college students elected to the Phi Beta Kappa Society on May 18, 2009. In the address, the author talks about the work he had done that might be of interest to these students. He emphasizes two kinds of work that are interlocking, yet distinct: (1) teaching; and (2)…

The upregulation of receptor activator NF-kappaB ligand expression by interleukin-1alpha and Porphyromonas endodontalis in human osteoblastic cells.

Science.gov (United States)

Chen, S-C; Huang, F-M; Lee, S-S; Li, M-Z; Chang, Y-C

2009-04-01

To investigate the receptor activator of nuclear factor-kappa B (NF-kappaB) ligand (RANKL) in osteoblastic cells stimulated with inflammatory mediators. The expression of RANKL in human osteoblastic cell line U2OS stimulated by pro-inflammatory cytokine interleukin (IL)-1alpha and black-pigmented bacteria Porphyromonas endodontalis was investigated by Western blot and enzyme-linked immunosorbent assay (ELISA). The significance of the results obtained from control and treated groups was statistically analysed by the paired Student's t-test. IL-1alpha was found to upregulate RANKL production in U2OS cells (P endodontalis also increased RANKL expression in U2OS cells after 4-h incubation period demonstrated by Western blot and ELISA (P endodontalis may be involved in developing apical periodontitis through the stimulation of RANKL production.

Suppressor of cytokine signalling (SOCS)-3 protects beta cells against IL-1beta-mediated toxicity through inhibition of multiple nuclear factor-kappaB-regulated proapoptotic pathways

DEFF Research Database (Denmark)

Karlsen, Allan Ertman; Heding, P E; Frobøse, H

2004-01-01

The proinflammatory cytokine IL-1beta induces apoptosis in pancreatic beta cells via pathways dependent on nuclear factor-kappaB (NF-kappaB), mitogen-activated protein kinase, and protein kinase C. We recently showed suppressor of cytokine signalling (SOCS)-3 to be a natural negative feedback reg...... regulator of IL-1beta- and IFN-gamma-mediated signalling in rat islets and beta cell lines, preventing their deleterious effects. However, the mechanisms underlying SOCS-3 inhibition of IL-1beta signalling and prevention against apoptosis remain unknown....

Non-equilibrium thermionic electron emission for metals at high temperatures

Science.gov (United States)

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

2015-08-01

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

Deuterium Values from Hydrated Volcanic Glass: A Paleoelevation Proxy for Oregon's Cascade Range

Science.gov (United States)

Carlson, T. B.; Bershaw, J. T.; Cassel, E. J.

2017-12-01

Deuterium ratios (δD) of hydrated volcanic glass have been used to reconstruct Cenozoic paleoenvironments. However, the reliability and proper sample preparation protocol have been debated. The Cascades are an excellent location to study the validity of hydrated volcanic glass as a paleoelevation proxy for several reasons. Moisture is largely derived from a single oceanic source and falls as orographic precipitation in the Cascades, leading to a characteristic altitude effect, or inverse relationship between elevation and the isotopic composition of meteoric water (δD). Additionally, past studies have inferred uplift of the Cascades since the Miocene based on changing fossil assemblages, tectonic models, and other isotopic proxies including soil carbonates and fossil teeth. In this study, hydrated volcanic ash samples from the lee of the Cascades were rinsed with hydrochloric acid and sonicated before glass shards were hand-selected and analyzed for δD and wt. % water. These preliminary results exhibited δD values becoming enriched with time, a trend opposite of other paleowater proxy studies in the area. A possible explanation for this trend is contamination due to inadequate removal of materials adhered to shard surfaces that can readily exchange with environmental water. Recent research asserts that hydrofluoric acid (HF) etching during sample preparation is necessary to accurately measure δD values of syndepositional water. Volcanic ash samples were reanalyzed after preparation using HF abrasion and heavy liquid separation. The data from these two subsets are interpreted in the context of modern water across the range, as well as other paleowater proxy and geologic studies to determine the implications of volcanic glass as a paleoelevation proxy in the Pacific Northwest.

NF-kappaB: Two Sides of the Same Coin.

Science.gov (United States)

Pires, Bruno R B; Silva, Rafael C M C; Ferreira, Gerson M; Abdelhay, Eliana

2018-01-09

Nuclear Factor-kappa B (NF-κB) is a transcription factor family that regulates a large number of genes that are involved in important physiological processes, including survival, inflammation, and immune responses. More recently, constitutive expression of NF-κB has been associated with several types of cancer. In addition, microorganisms, such as viruses and bacteria, cooperate in the activation of NF-κB in tumors, confirming the multifactorial role of this transcription factor as a cancer driver. Recent reports have shown that the NF-κB signaling pathway should receive attention for the development of therapies. In addition to the direct effects of NF-κB in cancer cells, it might also impact immune cells that can both promote or prevent tumor development. Currently, with the rise of cancer immunotherapy, the link among immune cells, inflammation, and cancer is a major focus, and NF-κB could be an important regulator for the success of these therapies. This review discusses the contrasting roles of NF-κB as a regulator of pro- and antitumor processes and its potential as a therapeutic target.

Intraobserver interpretation of breast ultrasonography following the BI-RADS classification

International Nuclear Information System (INIS)

Calas, M.J.G.; Almeida, R.M.V.R.; Gutfilen, B.; Pereira, W.C.A.

2010-01-01

Purpose: To use the BI-RADS ultrasound classification in an intraobserver retrospective study of the interpretation of breast images. Materials and Methods: The study used 40 breast ultrasound images recorded in orthogonal planes, obtained from patients with an indication for surgery. Eight professionals experienced in breast imaging analysis retrospectively reviewed these lesions, in three rounds of image interpretation (with a 3-6 months interval between rounds). Observers had no access to information from medical records or histopathological results, and, without their knowledge, in each new round were assigned the same images previously interpreted by them. Fleiss-modified Kappa measures were the study main concordance index. Besides the BI-RADS, a scale grouping its categories 2-3 and 4-5 was also used. The statistical analysis concerned the intraobserver agreement. Results: Kappa values ranged from 0.37 to 0.75 (original categories) and from 0.73 to 0.87 (grouped categories). Overall, out of the 8 observers, 7 presented moderate to substantial concordance (Kappa values 0.51 to 0.74). Conclusion: The BI-RADS is a reporting tool that provides a standardized terminology for US exams. In this study, moderate to substantial concordance in Kappa values was found, in agreement with other studies of the literature.

The inhibition of NF-kappaB activation pathways and the induction of apoptosis by dithiocarbamates in T cells are blocked by the glutathione precursor N-acetyl-L-cysteine

OpenAIRE

Fernandez, P C; Machado, J; Heussler, Volker; Botteron, C; Palmer, G H; Dobbelaere, D A

1999-01-01

Nuclear factor-kappaB regulates genes that control immune and inflammatory responses and are involved in the pathogenesis of several diseases, including AIDS and cancer. It has been proposed that reactive oxygen intermediates participate in NF-kappaB activation pathways, and compounds with putative antioxidant activity such as N-acetyl-L-cysteine (NAC) and pyrrolidine dithiocarbamate (PDTC) have been used interchangeably to demonstrate this point. We examined their effects, separately and com...

Buddleja officinalis suppresses high glucose-induced vascular smooth muscle cell proliferation: role of mitogen-activated protein kinases, nuclear factor-kappaB and matrix metalloproteinases.

Science.gov (United States)

Lee, Yun Jung; Kim, Jin Sook; Kang, Dae Gill; Lee, Ho Sub

2010-02-01

Diabetes mellitus is a well-established risk factor for vascular diseases caused by atherosclerosis. In the development of diabetic atherogenesis, vascular smooth muscle cell proliferation is recognized as a key event. Thus, we aimed to investigate whether an ethanol extract of Buddleja officinalis (EBO) suppresses high glucose-induced proliferation in primary cultured human aortic smooth muscle cells (HASMC). [(3)H]-thymidine incorporation revealed that incubation of HASMC with a high concentration of glucose (25 mmol/L) increased cell proliferation. The expression levels of cell cycle protein were also increased by treatment with high glucose concentration. Pretreatment of HASMC with EBO significantly attenuated the increase of high glucose-induced cell proliferation as well as p38 mitogen-activated protein kinases (MAPK) and JNK phosphorylation. EBO suppressed high glucose-induced matrix metalloproteinase (MMP)-9 activity in a dose-dependent manner. In addition, EBO suppressed nuclear factor-kappaB (NF-kappaB) nuclear translocation and transcriptional activity in high glucose conditions. Taken together, the present data suggest that EBO could suppress high glucose-induced atherosclerotic processes through inhibition of p38, JNK, NF-kappaB and MMP signal pathways in HASMC.

Tomosynthesis of the thoracic spine: added value in diagnosing vertebral fractures in the elderly.

Science.gov (United States)

Geijer, Mats; Gunnlaugsson, Eirikur; Götestrand, Simon; Weber, Lars; Geijer, Håkan

2017-02-01

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 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 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. • Tomosynthesis helps evaluate the thoracic spine in the elderly. • Observer agreement for thoracic spine tomosynthesis was substantial (mean κ = 0.73). • Significantly more vertebrae and significantly more fractures were seen with tomosynthesis. • Tomosynthesis took longer to evaluate than radiography. • There was a clear preference among all observers for tomosynthesis over radiography.

c-Jun NH2-terminal kinase activity in subcutaneous adipose tissue but not nuclear factor-kappaB activity in peripheral blood mononuclear cells is an independent determinant of insulin resistance in healthy individuals

DEFF Research Database (Denmark)

Sourris, Karly C; Lyons, Jasmine G; de Courten, Maximilian

2009-01-01

Chronic low-grade activation of the immune system (CLAIS) predicts type 2 diabetes via a decrease in insulin sensitivity. Our study investigated potential relationships between nuclear factor-kappaB (NF-kappaB) and c-Jun NH(2)-terminal kinase (JNK) pathways-two pathways proposed as the link between...

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

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Olav Rosef

2004-04-01

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

PCR-based clonality analysis of B-cell lymphomas in paraffin-embedded tissues: diagnostic value of immunoglobulin kappa and lambda light chain gene rearrangement investigation.

Science.gov (United States)

Amara, Khaled; Trimeche, Mounir; Ziadi, Sonia; Sriha, Badreddine; Mokni, Moncef; Korbi, Sadok

2006-01-01

Polymerase chain reaction (PCR)-based analysis, employed for detecting immunoglobulin heavy chain (IgH) gene rearrangements, has become a diagnostic tool widely used in the investigation of B-cell lymphomas, but the overall sensitivity of these methods does not exceed 80%, notably in germinal center (GC) and post-GC B-cell origin lymphomas. Many PCR strategies devised for detecting immunoglobulin light chain (IgL) gene rearrangements have been developed to enhance the clonality detection rates. However, the feasibility of these methods in routine clinical diagnosis using paraffin-embedded tissues has not yet been investigated sufficiently. We studied a large series of 108 cases of B-cell lymphomas, as well as 20 reactive lymphoid tissues using degenerate primers to amplify immunoglobulin kappa (Igkappa) and lambda (Iglambda) light chain genes. B-cell clonality was further investigated using semi-nested PCR for IgH gene rearrangements. B-cell clonality was detected in 74%, 56.5%, and 43.5% of cases using IgH, Igkappa, and Iglambda PCR, respectively. By combining these methods, the clonality detection rate increased to 93.5%. Only polyclonal patterns were noted in reactive lymphoid samples. We concluded that in addition to the established methods for IgH analysis, a PCR-based approach for IgL gene rearrangements analysis improves the clonality detection rate in over 90% of B-cell lymphoma cases using routine histological specimens with poor preservation of the genomic DNA.

Evaluating observer agreement of scoring systems for foot integrity and footrot lesions in sheep

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Foddai Alessandro

2012-05-01

Full Text Available Abstract Background A scoring scale with five ordinal categories is used for visual diagnosis of footrot in sheep and to study its epidemiology and control. More recently a 4 point ordinal scale has been used by researchers to score foot integrity (wall and sole horn damage in sheep. There is no information on observer agreement using either of these scales. Observer agreement for ordinal scores is usually estimated by single measure values such as weighted kappa or Kendall’s coefficient of concordance which provide no information where the disagreement lies. Modeling techniques such as latent class models provide information on both observer bias and whether observers have different thresholds at which they change the score given. In this paper we use weighted kappa and located latent class modeling to explore observer agreement when scoring footrot lesions (using photographs and videos and foot integrity (using post mortem specimens in sheep. We used 3 observers and 80 photographs and videos and 80 feet respectively. Results Both footrot and foot integrity scoring scales were more consistent within observers than between. The weighted kappa values between observers for both footrot and integrity scoring scales ranged from moderate to substantial. There was disagreement between observers with both observer bias and different thresholds between score values. The between observer thresholds were different for scores 1 and 2 for footrot (using photographs and videos and for all scores for integrity (both walls and soles. The within observer agreement was higher with weighted kappa values ranging from substantial to almost perfect. Within observer thresholds were also more consistent than between observer thresholds. Scoring using photographs was less variable than scoring using video clips or feet. Conclusions Latent class modeling is a useful method for exploring components of disagreement within and between observers and this information could

Hemin inhibits cyclooxygenase-2 expression through nuclear factor-kappa B activation and ornithine decarboxylase expression in 12-O-tetradecanoylphorbol-13-acetate-treated mouse skin

Energy Technology Data Exchange (ETDEWEB)

Park, Jae Hee; Lee, Chang Ki [Department of Oral Biology, Yonsei University College of Dentistry, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul 120-752 (Korea, Republic of); Oral Cancer Research Institute, Yonsei University College of Dentistry, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul 120-752 (Korea, Republic of); Hwang, Young Sun [Department of Applied Life Science and Brain Korea 21 Project, Yonsei University College of Dentistry, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul 120-752 (Korea, Republic of); Park, Kwang-Kyun [Department of Oral Biology, Yonsei University College of Dentistry, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul 120-752 (Korea, Republic of); Department of Applied Life Science and Brain Korea 21 Project, Yonsei University College of Dentistry, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul 120-752 (Korea, Republic of); Chung, Won-Yoon [Department of Oral Biology, Yonsei University College of Dentistry, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul 120-752 (Korea, Republic of); Department of Applied Life Science and Brain Korea 21 Project, Yonsei University College of Dentistry, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul 120-752 (Korea, Republic of)], E-mail: wychung@yuhs.ac

2008-07-03

Inflammation induced by various stimuli has been found to be associated with increased risk for most types of human cancer. Inflammation facilitates the initiation of normal cells, as well as the growth of initiated cells and their progression to malignancy through production of proinflammatory cytokines and diverse reactive oxygen/nitrogen species. These also activate the signaling molecules that are involved in inflammation and carcinogenesis. Our previous studies have demonstrated that hemin inhibited 7,12-dimethylbenz[a]anthracene (DMBA)-induced bacterial mutagenesis and oxidative DNA damage, reduced the level of DNA-DMBA adduct and 12-O-tetradecanoylphorobl-13-acetate (TPA)-induced tumor formation in DMBA-initiated ICR mouse skin, and inhibited myeloperoxidase and ornithine decarboxylase (ODC) activity and H{sub 2}O{sub 2} formation in TPA-treated mouse skin. In the present study, to further elucidate the molecular mechanisms underlying the chemopreventive activity of hemin, its effect on the expression of ODC and cyclooxygenase (COX)-2, and the activation of nuclear factor-kappa B (NF-{kappa}B) and mitogen-activated protein kinases (MAPKs) regulating these proteins were explored in mouse skin with TPA-induced inflammation. Topically applied hemin inhibited ear edema and epidermal thickness in mice treated with TPA. Pretreatment with hemin reduced the expression of ODC and COX-2, and also reduced NF-{kappa}B activation in TPA-stimulated mouse skin. In addition, hemin suppressed the TPA-induced activation of extracellular signal-regulated protein kinase (ERK) and p38 MAPK in a dose-dependent manner. Taken together, hemin inhibited TPA-induced COX-2 expression by altering NF-{kappa}B signaling pathway via ERK and p38 MAPK, as well as TPA-induced ODC expression in mouse skin. Thereby, hemin may be an attractive candidate for a chemopreventive agent.

Measurement of Michel Parameters ($\\bar\\eta$, $\\xi\\kappa$) in the radiative leptonic decay of tau at Belle

CERN Document Server

Abdesselam, A.

2017-06-22

We present the first measurement of the Michel parameters $\\bar{\\eta}$ and $\\xi\\kappa$ in the radiative leptonic decay of the $\\tau$ lepton using 703 f$\\mathrm{b}^{-1}$ of data collected with the Belle detector at the KEKB $e^+e^-$ collider. The Michel parameters are measured by an unbinned maximum likelihood fit to the kinematic information of $e^+e^-\\rightarrow\\tau^+\\tau^-\\rightarrow (\\pi^+\\pi^0 \\bar{\

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

Science.gov (United States)

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

2012-01-01

Background: Osteoclastogenesis is coordinated by the interaction of three members of the tumor necrosis factor (TNF) superfamily: Osteoprotegerin (OPG)/receptor activator of nuclear factor kappa B ligand (RANKL)/receptor activator of nuclear factor kappa B (RANK). The aim of this study was to investigate RANKL and OPG levels, and their relative ratio in gingival crevicular fluid (GCF) of patients with chronic and aggressive periodontitis, as well as healthy controls. Materials and Methods: In this analytical study, GCF was obtained from healthy (n = 10), mild chronic periodontitis (n = 18), moderate chronic periodontitis (n = 18), severe chronic periodontitis (n = 20), and generalized aggressive periodontitis (n = 20) subjects. RANKL and OPG concentrations were measured by enzyme-linked immunosorbent assay. Statistical tests used were Kruskal–Wallis test, Mann–Whitney U rank sum test, and Spearman's rank correlation analysis. The level of statistical significance was set at P chronic periodontitis (mild, moderate, severe), and aggressive periodontitis (P = 0.41). There was statistically significant correlation between the concentration of sRANKL and Clinical Attachment Level (CAL) in moderate chronic periodontitis patients (R = 0.48, P = 0.04). There was also negative correlation between OPG concentration and CAL in moderate chronic periodontitis patients, although not significant (R = −0.13). Conclusion: RANKL was prominent in periodontitis sites, especially in moderate periodontitis patients, whereas OPG was not detectable in some diseased sites with bleeding on probing, supporting the role of these two molecules in the bone loss developed in this disease. PMID:23559954

Expression of TLR-2, TLR-4, NOD2 and pNF-kappaB in a neonatal rat model of necrotizing enterocolitis.

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Aurelie Le Mandat Schultz

Full Text Available BACKGROUND: The etiology of necrotizing enterocolitis (NEC results from a combination of several risk factors that act synergistically and occurs in the same circumstances as those which lead to innate immunity activation. Pattern recognition molecules could be an important player in the initiation of an exaggerated inflammatory response leading to intestinal injury in NEC. METHODOLOGY/PRINCIPAL FINDINGS: We specifically evaluated intestinal epithelial cell (IEC expression of Toll-like receptor 2 (TLR-2, TLR-4, NOD2 and phosphorylated NF-kappaB (pNF-kappaB after mucosal injury in a rat model of NEC induced by prematurity, systemic hypoxia, and a rich protein formula. In the control group (group 1, neonatal rats were full-term and breast-fed; in the experimental groups, rat pups were preterm at day 21 of gestation and rat-milk fed (group 2 or hand-gavaged with a protein rich formula after a hypoxia-reoxygenation procedure (group 3. Morphological mucosal changes in the small bowel were scored on hematoxylin- and eosin-stained sections. Immunohistochemistry was performed on frozen tissue sections using anti TLR-2 and active pNF-kappaB p65 antibodies. Real-time RT-PCR was performed to assess mRNA expression of NOD2, TLR-2 and TLR-4. Proliferation and apoptosis were studied in paraffin sections using anti Ki-67 and caspase-3 antibodies, respectively. The combination of immaturity, protein rich formula and a hypoxia-reoxygenation procedure induces pathological mucosal damage consistent with NEC. There was an overexpression of TLR-2, and pNF-kappaB in IECs that was correlated with the severity of mucosal damage, together with an increase of apoptotic IECs and markedly impaired proliferation. In addition, these immunological alterations appeared before severe mucosal damage. TLR-2 mRNA were also increased in NEC together with TLR-4 mRNA using real-time RT-PCR whereas NOD2 expression was unchanged. CONCLUSIONS/SIGNIFICANCE: These results show that this

Precise Range Determination Using Laser Ranging Data of LAGEOS

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Kwang-Ryul Kim

1993-12-01

Full Text Available Satellite laser ranging observation of LAGEOS ¥± has been performed using the SLR System at Sheshan Laser Ranging Station, Shanghai Observatory. And we obtained 1,838 observational points The observed range data is corrected by means of system delay correction using ground target observation, atmospheric refraction delay correction, offset correction, general relativistic correction and tide correction including solid tide, polar tide and ocean tide. As a result, the determined range delay mean value is 19.12m and the mean internal accuracy by means of polynomial fitting and least square method is ¡¾7cm. Corrected observational points are 1,340 and noise ratio to total observational points is 27.1%

Inhibitors of nuclear factor kappa B cause apoptosis in cultured macrophages

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E. E. Mannick

1997-01-01

Full Text Available The precise role of the transcription factor nuclear factor kappa B (NF- κB in the regulation of cell survival and cell death is still unresolved and may depend on cell type and position in the cell cycle. The aim of this study was to determine if three pharmacologic inhibitors of NF-κB, pyrrolidine dithiocarbamate, N-tosyl-L-lysl chloromethyl ketone and calpain I inhibitor, induce apoptosis in a murine macrophage cell line (RAW 264.7 at doses similar to those required for NF-κB inhibition. We found that each of the three inhibitors resulted in a dose- and time-dependent increase in morphologic indices of apoptosis in unstimulated, LPS-stimulated and TNF-stimulated cells. Lethal doses were consistent with those required for NF- κB inhibition. We conclude that nuclear NF-κB activation may represent an important survival mechanism in macrophages.

The Mayo Dysphagia Questionnaire-30: documentation of reliability and validity of a tool for interventional trials in adults with esophageal disease.

Science.gov (United States)

McElhiney, Judith; Lohse, Matthew R; Arora, Amindra S; Peloquin, Joanna M; Geno, Debra M; Kuntz, Melissa M; Enders, Felicity B; Fredericksen, Mary; Abdalla, Adil A; Khan, Yulia; Talley, Nicholas J; Diehl, Nancy N; Beebe, Timothy J; Harris, Ann M; Farrugia, Gianrico; Graner, Darlene E; Murray, Joseph A; Locke, G Richard; Grothe, Rayna M; Crowell, Michael D; Francis, Dawn L; Grudell, April M B; Dabade, Tushar; Ramirez, Angelica; Alkhatib, MhdMaan; Alexander, Jeffrey A; Kimber, Jessica; Prasad, Ganapathy; Zinsmeister, Alan R; Romero, Yvonne

2010-09-01

The aim of this study was to develop the Mayo Dysphagia Questionnaire-30 Day (MDQ-30), a tool to measure esophageal dysphagia, by adapting items from validated instruments for use in clinical trials, and assess its feasibility, reproducibility, and concurrent validity. Outpatients referred to endoscopy for dysphagia or seen in a specialty clinic were recruited. Feasibility testing was done to identify problematic items. Reproducibility was measured by test-retest format. Concurrent validity reflects agreement between information gathered in a structured interview versus the patients' written responses. The MDQ-30, a 28-item instrument, took 10 min (range = 5-30 min) to complete. Four hundred thirty-one outpatients [210 (49%) men; mean age = 61 years] participated. Overall, most concurrent validity kappa values for dysphagia were very good to excellent with a median of 0.78 (min 0.28, max 0.95). The majority of reproducibility kappa values for dysphagia were moderate to excellent with a median kappa value of 0.66 (min 0.07, max 1.0). Overall, concurrent validity and reproducibility kappa values for gastroesophageal reflux disease (GERD) symptoms were 0.81 (95% CI = 0.72, 0.91) and 0.66 (95% CI = 0.55, 0.77), respectively. Individual item percent agreement was generally very good to excellent. Internal consistency was excellent. We conclude that the MDQ-30 is an easy-to-complete tool to evaluate reliably dysphagia symptoms over the last 30 days.

Curcumin Based Drug Screening for Inhibitors of NF kappa B in a Cell Model of Prostate Cancer Progression

Science.gov (United States)

2008-02-01

identify new and structurally diverse chemical analogs of the polyphenolic phytochemical Curcumin from the Indian herb Curcuma longa (family...AD_________________ Award Number: W81XWH-07-1-0081 TITLE: Curcumin Based Drug Screening for... Curcumin Based Drug Screening for Inhibitors of NF kappa B in a Cell Model of Prostate Cancer Progression 5b. GRANT NUMBER W81XWH-07-1-0081 5c

Quantitative assessment of bone marrow attenuation values at MDCT: An objective tool for the detection of bone bruise related to occult sacral insufficiency fractures

Energy Technology Data Exchange (ETDEWEB)

Henes, F.O.; Groth, M.; Bley, T.A.; Regier, M.; Ittrich, H.; Adam, G.; Bannas, P. [University Medical Center Hamburg-Eppendorf, Department of Diagnostic and Interventional Radiology, Hamburg (Germany); Nuechtern, J.V. [University Medical Center Hamburg-Eppendorf, Department of Trauma, Hand and Reconstructive Surgery, Hamburg (Germany); Treszl, A. [University Medical Center Hamburg-Eppendorf, Center for Experimental Medicine, Department of Medical Biometry and Epidemiology, Hamburg (Germany)

2012-10-15

To prove the feasibility of using Hounsfield attenuation values at MDCT to detect bone bruises related to sacral insufficiency fractures. Twenty-two patients with acute sacrum trauma and no fracture findings at MDCT were included in our prospective study. Two observers independently reviewed CTs regarding visual signs of bone bruises in 132 defined regions of the sacral alae. Interobserver agreement was tested by {kappa} statistics. Subsequently, HU values were obtained in the same regions, and attenuation differences between the two sides were calculated. Validity and reliability were assessed by intraclass correlation coefficient and Bland-Altman analysis. HU differences were subjected to ROC curve analysis to determine sensitivity, specificity, PPV and NPV. MRI served as standard reference. MRI revealed 19 regions with bone bruises and associated sacral insufficiency fractures. HU measurements demonstrated good validity and reliability (r = 0.989). ROC curve analysis exhibited an ideal cutoff value of 35.7 HU density difference between affected and non-affected regions. Visual evaluation revealed moderate agreement ({kappa} = 0.48); diagnostic accuracy was inferior to objective evaluation. Assessment of differences in bone marrow density by HU measurements is an objective and reliable tool for detection of bone bruises associated with occult sacral insufficiency fractures. (orig.)

Kappa Cygnids (KCG) by TV observation results

Science.gov (United States)

Shiba, Yasuo

2017-12-01

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

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

Science.gov (United States)

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

2018-04-14

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

Tibiofibular syndesmosis in acute ankle fractures: additional value of an oblique MR image plane

Energy Technology Data Exchange (ETDEWEB)

Hermans, John J.; Ginai, Abida Z. [Erasmus University Medical Center, Department of Radiology, Rotterdam (Netherlands); Beumer, Annechien; Moonen, Adrianus F.C.M. [Amphia Hospital, Department of Orthopaedics, Breda (Netherlands); Hop, Wim C.J. [Erasmus University Medical Center, Department of Biostatistics, Rotterdam (Netherlands)

2012-02-15

To evaluate the additional value of a 45 oblique MRI scan plane for assessing the anterior and posterior distal tibiofibular syndesmotic ligaments in patients with an acute ankle fracture. Prospectively, data were collected for 44 consecutive patients with an acute ankle fracture who underwent a radiograph (AP, lateral, and mortise view) as well as an MRI in both the standard three orthogonal planes and in an additional 45 oblique plane. The fractures on the radiographs were classified according to Lauge-Hansen (LH). The anterior (ATIFL) and posterior (PTIFL) distal tibiofibular ligaments, as well as the presence of a bony avulsion in both the axial and oblique planes was evaluated on MRI. MRI findings regarding syndesmotic injury in the axial and oblique planes were compared to syndesmotic injury predicted by LH. Kappa and the agreement score were calculated to determine the interobserver agreement. The Wilcoxon signed rank test and McNemar's test were used to compare the two scan planes. The interobserver agreement ({kappa}) and agreement score [AS (%)] regarding injury of the ATIFL and PTIFL and the presence of a fibular or tibial avulsion fracture were good to excellent in both the axial and oblique image planes ({kappa} 0.61-0.92, AS 84-95%). For both ligaments the oblique image plane indicated significantly less injury than the axial plane (p < 0.001). There was no significant difference in detection of an avulsion fracture in the axial or oblique plane, neither anteriorly (p=0.50) nor posteriorly (p=1.00). With syndesmotic injury as predicted by LH as comparison, the specificity in the oblique MR plane increased for both anterior (to 86% from 7%) and posterior (to 86% from 48%) syndesmotic injury when compared to the axial plane. Our results show the additional value of an 45 oblique MR image plane for detection of injury of the anterior and posterior distal tibiofibular syndesmoses in acute ankle fractures. Findings of syndesmotic injury in the oblique

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

Science.gov (United States)

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

2018-01-01

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

Serum Free Light Chains in Neoplastic Monoclonal Gammopathies: Relative Under-Detection of Lambda Dominant Kappa/Lambda Ratio, and Underproduction of Free Lambda Light Chains, as Compared to Kappa Light Chains, in Patients With Neoplastic Monoclonal Gammopathies.

Science.gov (United States)

Lee, Won Sok; Singh, Gurmukh

2018-07-01

Quantitative evaluation of serum free light chains is recommended for the work up of monoclonal gammopathies. Immunoglobulin light chains are generally produced in excess of heavy chains. In patients with monoclonal gammopathy, κ/λ ratio is abnormal less frequently with lambda chain lesions. This study was undertaken to ascertain if the levels of overproduction of the two light chain types and their detection rates are different in patients with neoplastic monoclonal gammopathies. Results of serum protein electrophoresis (SPEP), serum protein immunofixation electrophoresis (SIFE), urine protein electrophoresis (UPEP), urine protein immunofixation electrophoresis (UIFE), and serum free light chain assay (SFLCA) in patients with monoclonal gammopathies were examined retrospectively. The κ/λ ratios were appropriately abnormal more often in kappa chain lesions. Ratios of κ/λ were normal in about 25% of patients with lambda chain lesions in whom free homogenous lambda light chains were detectable in urine. An illustrative case suggests underproduction of free lambda light chains, in some instances. The lower prevalence of lambda dominant κ/λ ratio in lesions with lambda light chains is estimated to be due to relative under-detection of lambda dominant κ/λ ratio in about 25% of the patients and because lambda chains are not produced in as much excess of heavy chains as are kappa chains, in about 5% of the patients. The results question the medical necessity and clinical usefulness of the serum free light chain assay. UPEP/UIFE is under-utilized.

A new assay format for NF-kappaB based on a DNA triple helix and a fluorescence resonance energy transfer.

Science.gov (United States)

Altevogt, Dominik; Hrenn, Andrea; Kern, Claudia; Clima, Lilia; Bannwarth, Willi; Merfort, Irmgard

2009-10-07

Herein we report a feasibility study for a new concept to detect DNA binding protein NF-kappaB based on a DNA triple helix formation in combination with a fluorescence resonance energy transfer (FRET). The new principle avoids expensive antibodies and radioactivity and might have implications for assays of other DNA binding proteins.

NF-kappa B modulation is involved in celastrol induced human multiple myeloma cell apoptosis.

Directory of Open Access Journals (Sweden)

Haiwen Ni

Full Text Available Celastrol is an active compound extracted from the root bark of the traditional Chinese medicine Tripterygium wilfordii Hook F. To investigate the effect of celastrol on human multiple myeloma cell cycle arrest and apoptosis and explore its molecular mechanism of action. The activity of celastrol on LP-1 cell proliferation was detected by WST-8 assay. The celastrol-induced cell cycle arrest was analyzed by flow cytometry after propidium iodide staining. Nuclear translocation of the nuclear factor kappa B (NF-κB was observed by fluorescence microscope. Celastrol inhibited cell proliferation of LP-1 myeloma cell in a dose-dependent manner with IC50 values of 0.8817 µM, which was mediated through G1 cell cycle arrest and p27 induction. Celastrol induced apoptosis in LP-1 and RPMI 8226 myeloma cells in a time and dose dependent manner, and it involved Caspase-3 activation and NF-κB pathway. Celastrol down-modulated antiapoptotic proteins including Bcl-2 and survivin expression. The expression of NF-κB and IKKa were decreased after celastrol treatment. Celastrol effectively blocked the nuclear translocation of the p65 subunit and induced human multiple myeloma cell cycle arrest and apoptosis by p27 upregulation and NF-kB modulation. It has been demonstrated that the effect of celastrol on NF-kB was HO-1-independent by using zinc protoporphyrin-9 (ZnPPIX, a selective heme oxygenase inhibitor. From the results, it could be inferred that celastrol may be used as a NF-kB inhibitor to inhibit myeloma cell proliferation.

Determination of the exact range of the value of the parameter corresponding to chaos based on the Silnikov criterion

International Nuclear Information System (INIS)

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

2010-01-01

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. (general)

Reprodutibilidade de um questionário de consumo alimentar para crianças em idade escolar Reproducibility of a typical day food choices questionnaire for schoolchildren

Directory of Open Access Journals (Sweden)

Adriana Soares Lobo

2008-03-01

percentage agreement (%CC and the adjusted kappa statistic. RESULTS: in public schools, %CC values ranged from 69% (bread to 84.5% (fish, and kappa values from 0.38 (bread to 0.69 (fish. In private schools, %CC values ranged from 73.9% (bread to 91.6% (beans and kappa values from 0.48 (bread to 0.83 (beans. In analyses stratified according to grade, %CC and kappa values were better for third and fourth grades compared to first and second grades in both public and private schools. CONCLUSIONS: the reproducibility of the questionnaire was demonstrated for elementary schoolchildren in private and public schools, but the former presented better results.

Good interobserver agreement was attainable on outcome adjudication in patients with stable coronary heart disease

DEFF Research Database (Denmark)

Kjoller, Erik; Hilden, Jorgen; Winkel, Per

2012-01-01

, unstable angina pectoris, and acute myocardial infarction were treated as one, agreement increased minimally. For fatal outcomes, the pairwise kappa values ranged from 0.65 to 0.90. The three adjudicators had 12%, 9%, and 10% of their death classifications overruled. CONCLUSION: Specialists in cardiology...

Multidetector CT of Locally Invasive Advanced Gastric Cancer: Value of Oblique Coronal Reconstructed Images for the Assessment of Local Invasion

Energy Technology Data Exchange (ETDEWEB)

Jung, Jin Hee; Kim, Ah Yong; Kim, Hye Jin; Yook, Jeong Hwan; Yu, Eun Sil; Jang, Yoon Jin; Park, Seong Ho; Shin, Yong Moon; Ha, Hyun Kwon [Asan Medical Center, Seoul (Korea, Republic of)

2010-01-15

To evaluate the diagnostic value of oblique coronal reconstructed CT images to determine the local invasion of advanced gastric cancer (AGC). Thirty-four consecutive patients, who were suspected to have locally invasive advanced gastric cancer (more than T3 stage) on a preoperative MDCT scan and underwent a diagnostic or curative laparotomy, were enrolled in this study. Two reviewers performed an independent blind review of three series of MDCT images in random order; axial (AXI), conventional coronal (CCI), and oblique coronal (OCI) (parallel to long axis of gastric body and pancreas) images. In assessing the local invasion, the reader's confidence for the local invasion of AGC was graded using a five point scale (1 = definitely negative, 5 = definitely positive: T4). With surgical findings and histopathological proofs as reference standards, the diagnostic performance of the three different plans of CT images was employed for the verification of local invasion of AGC on a preoperative CT scan using the receiver operating characteristic (ROC) method. Agreements between the two reviewers were analyzed using weighted kappa statistics. Results: In 19 out of 34 patients, local invasion was confirmed surgically or histopathologically (13 pancreas invasion, 6 liver invasion, 4 major vascular invasion, 3 colon and mesocolon invasion, and 2 spleen invasion). The diagnostic performance of OCI was superior to AXI or CCI in the local invasion of AGC. The differences in the area under the curve of AXI (0.770 {+-} 0.087, 0.700 {+-} 0.094), CCI (0.884 {+-} 0.058, 0.958 {+-} 0.038), and OCI (0.954 {+-} 0.050, 0.956 {+-} 0.049), were statistically significant for both reviewers. Inter-observer agreement was excellent for OCI ({kappa}= .973), which was greater than CCI (({kappa}= .839), and AXI (({kappa}= .763). On a CT scan, OCI might be a useful imaging technique in evaluating locally invasive advanced gastric cancer.

Impedimetric aptasensor for nuclear factor kappa B with peroxidase-like mimic coupled DNA nanoladders as enhancer.

Science.gov (United States)

Peng, Kanfu; Zhao, Hongwen; Xie, Pan; Hu, Shuang; Yuan, Yali; Yuan, Ruo; Wu, Xiongfei

2016-07-15

In this work, we developed a sensitive and universal aptasensor for nuclear factor kappa B (NF-κB) detection based on peroxidase-like mimic coupled DNA nanoladders for signal amplification. The dsDNA formed by capture DNA S1 and NF-κB binding aptamer (NBA) was firstly assembled on electrode surface. The presence of target NF-κB then led to the leave of NBA from electrode surface and thus provided the binding sites for immobilizing initiator to trigger in situ formation of DNA nanoladders on electrode surface. Since the peroxidase-like mimic manganese (III) meso-tetrakis (4-Nmethylpyridyl)-porphyrin (MnTMPyP) interacts with DNA nanoladders via groove binding, the insoluble benzo-4-chlorohexadienone (4-CD) precipitation derived from the oxidation of 4-chloro-1-naphthol (4-CN) could be formed on electrode surface in the presence of H2O2, resulting in a significantly amplified EIS signal output for quantitative target analysis. As a result, the developed aptasensor showed a low detection limit of 7pM and a wide linear range of 0.01-20nM. Featured with high sensitivity and label-free capability, the proposed sensing scheme can thus offer new opportunities for achieving sensitive, selective and stable detection of different types of target proteins. Copyright © 2016 Elsevier B.V. All rights reserved.

[Effects of TCM treatment according to syndrome differentiation on expressions of nuclear factor-kappaB and gamma-glutamylcysteine synthetase in rats with chronic obstructive pulmonary disease of various syndrome types].

Science.gov (United States)

Zhang, Wei; Zhang, Xin-Yue; Shao, Yu-Meng

2007-05-01

To explore the mechanism of traditional Chinese medicine (TCM) treatment according to syndrome differentiation in treating chronic obstructive pulmonary disease (COPD) by observing the changes of nuclear factor-kappaB (NF-kappaB) and gamma-glutamylcysteine synthetase (gamma-GCS) expression levels in rats. COPD model was established by modified method of combining fumigation and lipopolysaccharide (LPS) intra-tracheal dripping. Model rats were treated respectively for succesive 14 days according to their syndrome, that is, Xiaoqinglong Decoction to the rats of cold-phlegm accumulation in Fei, Maxing Shigan Decoction to those of heat-phlegm accumulation in Fei, Yupingfeng Decoction to those of Fei-qi deficiency, Liujunzi Decoction to those of Pi-qi deficiency, Renshen Gejie Decoction to those of Shen qi-deficiency. Besides, model rats in the model control group received 2mL normal saline daily, and no intervention was applied in the normal control group. The expression of gamma-GCS and NF-kappaB was detected by immunochemistry before and after treatment. Compared with that in the normal rats, the expressions of gamma-GCS and NF-kappaB in bronchial and alveolar epithelium of COPD rats before treatment were significantly higher, but the positive expression rates were lowered after treatment significantly (Psyndrome differentiation could rectify imbalance of oxidation/anti-oxidation and alleviate inflammatory reaction in COPD rats, thus to treat COPD effectively.

Dietary (1-->3), (1-->4)-beta-D-glucans from oat activate nuclear factor-kappaB in intestinal leukocytes and enterocytes from mice

NARCIS (Netherlands)

Volman, Julia J.; Mensink, Ronald P.; Ramakers, Julian D.; de Winther, Menno P.; Carlsen, Harald; Blomhoff, Rune; Buurman, Wim A.; Plat, Jogchum

2010-01-01

Dietary components, like beta-glucans, can modulate the intestinal immune response. We previously showed that fecal water enriched with oat beta-glucan stimulated the cytokine-induced immune response of enterocytes. It is, however, unclear whether beta-glucans activate nuclear factor-kappaB

Endotoxin/lipopolysaccharide activates NF-kappa B and enhances tumor cell adhesion and invasion through a beta 1 integrin-dependent mechanism.

LENUS (Irish Health Repository)

Wang, Jiang Huai

2012-02-03

Beta(1) integrins play a crucial role in supporting tumor cell attachment to and invasion into the extracellular matrix. Endotoxin\\/LPS introduced by surgery has been shown to enhance tumor metastasis in a murine model. Here we show the direct effect of LPS on tumor cell adhesion and invasion in extracellular matrix proteins through a beta(1) integrin-dependent pathway. The human colorectal tumor cell lines SW480 and SW620 constitutively expressed high levels of the beta(1) subunit, whereas various low levels of alpha(1), alpha(2), alpha(4), and alpha(6) expression were detected. SW480 and SW620 did not express membrane-bound CD14; however, LPS in the presence of soluble CD14 (sCD14) significantly up-regulated beta(1) integrin expression; enhanced tumor cell attachment to fibronectin, collagen I, and laminin; and strongly promoted tumor cell invasion through the Matrigel. Anti-beta(1) blocking mAbs (4B4 and 6S6) abrogated LPS- plus sCD14-induced tumor cell adhesion and invasion. Furthermore, LPS, when combined with sCD14, resulted in NF-kappaB activation in both SW480 and SW620 cells. Inhibition of the NF-kappaB pathway significantly attenuated LPS-induced up-regulation of beta(1) integrin expression and prevented tumor cell adhesion and invasion. These results provide direct evidence that although SW480 and SW620 cells do not express membrane-bound CD14, LPS in the presence of sCD14 can activate NF-kappaB, up-regulate beta(1) integrin expression, and subsequently promote tumor cell adhesion and invasion. Moreover, LPS-induced tumor cell attachment to and invasion through extracellular matrix proteins is beta(1) subunit-dependent.

Muon-spin rotation studies of the flux lattice in {kappa}-(BEDT-TTF){sub 2}Cu(SCN){sub 2}

Energy Technology Data Exchange (ETDEWEB)

Lee, S.L. [Saint Andrews Univ. (United Kingdom). Sch. of Phys. and Astron.; Blundell, S.J. [Oxford Univ. (United Kingdom). Dept. of Physics; Pratt, F.L. [RIKEN-RAL, Didcot (United Kingdom); Pattenden, P.A. [Oxford Univ. (United Kingdom). Dept. of Physics; Forgan, E.M. [Birmingham Univ. (United Kingdom). School of Physics and Space Research; Sasaki, T. [Tohoku Univ., Sendai (Japan). Inst. for Materials Research; Aegerter, C.M. [Zurich Univ. (Switzerland). Inst. fuer Physik; Hunt, M. [Zurich Univ. (Switzerland). Inst. fuer Physik; Chow, K.H. [Oxford Univ. (United Kingdom). Dept. of Physics; Hayes, W. [Oxford Univ. (United Kingdom). Dept. of Physics; Singleton, J. [Oxford Univ. (United Kingdom). Dept. of Physics; Keller, H. [Zurich Univ. (Switzerland). Inst. fuer Physik; Savic, I.M. [Zurich Univ. (Switzerland). Inst. fuer Physik

1997-02-15

Muon spin rotation ({mu}SR) studies of the vortex lattice in the superconductor {kappa}-(BEDT-TTF){sub 2}Cu(SCN){sub 2} have revealed a crossover from a quasi-2d to a vortex-line lattice structure for fields below a characteristic field B{sub cr}. The {mu}SR-lineshapes measured from the vortex-line lattice have allowed a re-evaluation of the in-plane penetration depth. (orig.)

Betting on Teachers: The 43rd Annual Phi Delta Kappa/Gallup Poll of the Public's Attitudes toward the Public Schools

Science.gov (United States)

Bushaw, William J.; Lopez, Shane J.

2011-01-01

This is the latest in a series of polls sponsored by Phi Delta Kappa International with the Gallup organization. Some important findings of this year's poll include: About half of us believe teacher unions are hurting public education, but we're more likely to support teacher union leaders than governors in disputes over teacher collective…

Turkish Scorzonera Species Extracts Attenuate Cytokine Secretion via Inhibition of NF-kappa B Activation, Showing Anti-Inflammatory Effect in Vitro

Czech Academy of Sciences Publication Activity Database

Acikara, O. B.; Hošek, J.; Babula, P.; Cvačka, Josef; Buděšínský, Miloš; Dračínský, Martin; Iscan, G. S.; Kadlecová, D.; Ballová, L.; Šmejkal, K.

2016-01-01

Roč. 21, č. 1 (2016), č. článku 43. ISSN 1420-3049 Institutional support: RVO:61388963 Keywords : anti-inflammatory activity * IL-1 beta * NF-kappa B * Scorzonera * phenolic * TNF-alpha * triterpen Subject RIV: CC - Organic Chemistry Impact factor: 2.861, year: 2016 http://www.mdpi.com/1420-3049/21/1/43/htm

JANEX-1, a JAK3 inhibitor, protects pancreatic islets from cytokine toxicity through downregulation of NF-{kappa}B activation and the JAK/STAT pathway

Energy Technology Data Exchange (ETDEWEB)

Lv, Na; Kim, Eun-Kyung; Song, Mi-Young [Department of Biochemistry, Medical School and Diabetes Research Center, Chonbuk National University, Jeonju, Jeonbuk 561-756 (Korea, Republic of); Choi, Ha-Na; Moon, Woo Sung [Department of Pathology, Medical School and Diabetes Research Center, Chonbuk National University, Jeonju, Jeonbuk 561-756 (Korea, Republic of); Park, Sung-Joo [Department of Herbology, School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Park, Jin-Woo [Department of Biochemistry, Medical School and Diabetes Research Center, Chonbuk National University, Jeonju, Jeonbuk 561-756 (Korea, Republic of); Kwon, Kang-Beom, E-mail: desson@wonkwang.ac.kr [Department of Physiology, School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Park, Byung-Hyun, E-mail: bhpark@chonbuk.ac.kr [Department of Biochemistry, Medical School and Diabetes Research Center, Chonbuk National University, Jeonju, Jeonbuk 561-756 (Korea, Republic of)

2009-07-15

JANEX-1/WHI-P131, a selective Janus kinase 3 (JAK3) inhibitor, has been shown to delay the onset of diabetes in the NOD mouse model. However, the molecular mechanism by which JANEX-1 protects pancreatic {beta}-cells is unknown. In the current study, we investigated the role of JANEX-1 on interleukin (IL)-1{beta} and interferon (IFN)-{gamma}-induced {beta}-cell damage using isolated islets. JANEX-1-pretreated islets showed resistance to cytokine toxicity, namely suppressed nitric oxide (NO) production, reduced inducible form of NO synthase (iNOS) expression, and decreased islet destruction. The molecular mechanism by which JANEX-1 inhibits iNOS expression was mediated through suppression of the nuclear factor {kappa}B (NF-{kappa}B) and JAK/signal transducer and activator of transcription (STAT) pathways. Islets treated with the cytokines downregulated the protein levels of suppressor of cytokine signaling (SOCS)-1 and SOCS-3, but pretreatment with JANEX-1 attenuated these decreases. Additionally, islets from JAK3{sup -/-} mice were more resistant to cytokine toxicity than islets from control mice. These results demonstrate that JANEX-1 protects {beta}-cells from cytokine toxicity through suppression of the NF-{kappa}B and JAK/STAT pathways and upregulation of SOCS proteins, suggesting that JANEX-1 may be used to preserve functional {beta}-cell mass.

Correlation between tissue metabolism and cellularity assessed by standardized uptake value and apparent diffusion coefficient in peritoneal metastasis.

Science.gov (United States)

Yu, Xue; Lee, Elaine Yuen Phin; Lai, Vincent; Chan, Queenie

2014-07-01

To evaluate the correlation between standardized uptake value (SUV) (tissue metabolism) and apparent diffusion coefficient (ADC) (water diffusivity) in peritoneal metastases. Patients with peritoneal dissemination detected on (18)F-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT) were prospectively recruited for MRI examinations with informed consent and the study was approved by the local Institutional Review Board. FDG-PET/CT, diffusion-weighted imaging (DWI), MRI, and DWI/MRI images were independently reviewed by two radiologists based on visual analysis. SUVmax/SUVmean and ADCmin/ADCmean were obtained manually by drawing ROIs over the peritoneal metastases on FDG-PET/CT and DWI, respectively. Diagnostic characteristics of each technique were evaluated. Pearson's coefficient and McNemar and Kappa tests were used for statistical analysis. Eight patients were recruited for this prospective study and 34 peritoneal metastases were evaluated. ADCmean was significantly and negatively correlated with SUVmax (r = -0.528, P = 0.001) and SUVmean (r = -0.548, P = 0.001). ADCmin had similar correlation with SUVmax (r = -0.508, P = 0.002) and SUVmean (r = -0.513, P = 0.002). DWI/MRI had high diagnostic performance (accuracy = 98%) comparable to FDG-PET/CT, in peritoneal metastasis detection. Kappa values were excellent for all techniques. There was a significant inverse correlation between SUV and ADC. © 2013 Wiley Periodicals, Inc.

Improved efficacy of soluble human receptor activator of nuclear factor kappa B (RANK) fusion protein by site-directed mutagenesis.

Science.gov (United States)

Son, Young Jun; Han, Jihye; Lee, Jae Yeon; Kim, HaHyung; Chun, Taehoon

2015-06-01

Soluble human receptor activator of nuclear factor kappa B fusion immunoglobulin (hRANK-Ig) has been considered as one of the therapeutic agents to treat osteoporosis or diseases associated with bone destruction by blocking the interaction between RANK and the receptor activator of nuclear factor kappa B ligand (RANKL). However, no scientific record showing critical amino acid residues within the structural interface between the human RANKL and RANK complex is yet available. In this study, we produced several mutants of hRANK-Ig by replacement of amino acid residue(s) and tested whether the mutants had increased binding affinity to human RANKL. Based on the results from flow cytometry and surface plasmon resonance analyses, the replacement of E(125) with D(125), or E(125) and C(127) with D(125) and F(127) within loop 3 of cysteine-rich domain 3 of hRANK-Ig increases binding affinity to human RANKL over the wild-type hRANK-Ig. This result may provide the first example of improvement in the efficacy of hRANK-Ig by protein engineering and may give additional information to understand a more defined structural interface between hRANK and RANKL.

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

Science.gov (United States)

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

2016-02-01

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

Forecasting Kp from solar wind data: input parameter study using 3-hour averages and 3-hour range values

Science.gov (United States)

Wintoft, Peter; Wik, Magnus; Matzka, Jürgen; Shprits, Yuri

2017-11-01

We have developed neural network models that predict Kp from upstream solar wind data. We study the importance of various input parameters, starting with the magnetic component Bz, particle density n, and velocity V and then adding total field B and the By component. As we also notice a seasonal and UT variation in average Kp we include functions of day-of-year and UT. Finally, as Kp is a global representation of the maximum range of geomagnetic variation over 3-hour UT intervals we conclude that sudden changes in the solar wind can have a big effect on Kp, even though it is a 3-hour value. Therefore, 3-hour solar wind averages will not always appropriately represent the solar wind condition, and we introduce 3-hour maxima and minima values to some degree address this problem. We find that introducing total field B and 3-hour maxima and minima, derived from 1-minute solar wind data, have a great influence on the performance. Due to the low number of samples for high Kp values there can be considerable variation in predicted Kp for different networks with similar validation errors. We address this issue by using an ensemble of networks from which we use the median predicted Kp. The models (ensemble of networks) provide prediction lead times in the range 20-90 min given by the time it takes a solar wind structure to travel from L1 to Earth. Two models are implemented that can be run with real time data: (1) IRF-Kp-2017-h3 uses the 3-hour averages of the solar wind data and (2) IRF-Kp-2017 uses in addition to the averages, also the minima and maxima values. The IRF-Kp-2017 model has RMS error of 0.55 and linear correlation of 0.92 based on an independent test set with final Kp covering 2 years using ACE Level 2 data. The IRF-Kp-2017-h3 model has RMSE = 0.63 and correlation = 0.89. We also explore the errors when tested on another two-year period with real-time ACE data which gives RMSE = 0.59 for IRF-Kp-2017 and RMSE = 0.73 for IRF-Kp-2017-h3. The errors as function

DMPD: Manipulation of mitogen-activated protein kinase/nuclear factor-kappaB-signalingcascades during intracellular Toxoplasma gondii infection. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 15361242 Manipulation of mitogen-activated protein kinase/nuclear factor-kappaB-sig...mmunol Rev. 2004 Oct;201:191-205. (.png) (.svg) (.html) (.csml) Show Manipulation of mitogen-activated prote... gondii infection. PubmedID 15361242 Title Manipulation of mitogen-activated protein kinase/nuclear factor-k

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

Science.gov (United States)

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

2018-05-01

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

Kappa-casein micelles: structure, interaction and gelling studied by small-angle neutron scattering.

Science.gov (United States)

de Kruif, C G; May, R P

1991-09-01

Small-angle neutron scattering (SANS) measurements on dilute and concentrated dispersions of kappa-casein micelles in a buffer at pH = 6.7 were made using the D11 diffractometer in Grenoble. Results indicate that the micelles have a dense core with a fluffy outer layer. This outer layer appears to give rise to a steeply repulsive interaction on contact. In fact, the hard-sphere model best fits the measured scattering intensities. Adding chymosin to the dispersion initiated a fractal flocculation of the micelles and consecutively a coalescence of the micelles. This unexpected second process resembled that of spinodal demixing. The dispersion phase thus separates into a water and a protein phase on a time scale of hours. The observed phenomona contribute to the understanding of the cheese-making process.

Interobserver agreement in the histologic diagnosis of colorectal polyps. the experience of the multicenter adenoma colorectal study (SMAC).

Science.gov (United States)

Costantini, Massimo; Sciallero, Stefania; Giannini, Augusto; Gatteschi, Beatrice; Rinaldi, Paolo; Lanzanova, Giuseppe; Bonelli, Luigina; Casetti, Tino; Bertinelli, Elisabetta; Giuliani, Orietta; Castiglione, Guido; Mantellini, Paola; Naldoni, Carlo; Bruzzi, Paolo

2003-03-01

Current clinical practice guidelines for patients with colorectal polyps are mainly based on the histologic characteristics of their lesions. However, interobserver variability in the assessment of specific polyp characteristics was evaluated in very few studies. The purpose of this study was to evaluate the interobserver agreement of four pathologists in the diagnosis of histologic type of colorectal polyps and in the degree of dysplasia and of infiltrating carcinoma in adenomas. A stratified random sample of 100 polyps was obtained from the 4,889 polyps resected within the Multicentre Adenoma Colorectal Study (SMAC), and the slides were blindly reviewed by the four pathologists. Agreement was analyzed using kappa statistics. A median kappa of 0.89 (range 0.79-1.0) was estimated for the interobserver agreement for the diagnosis of hyperplastic polyp vs. adenoma. The agreement in the diagnosis of tubular, tubulovillous, and villous type, was given by median kappa values of 0.50, 0.15, and 0.36, respectively. The median kappa for the diagnosis of infiltrating carcinoma was 0.78 (range 0.73-0.84). Agreement on diagnosis of adenoma histologic subtypes, degrees of dysplasia, or infiltrating carcinoma in adenoma was moderate. A simpler classifications might help to better identify patients at different risk of colorectal cancer.

The plant limonoid 7-oxo-deacetoxygedunin inhibits RANKL-induced osteoclastogenesis by suppressing activation of the NF-{kappa}B and MAPK pathways

Energy Technology Data Exchange (ETDEWEB)

Wisutsitthiwong, Chonnaree; Buranaruk, Chayanit [Graduate Program in Industrial Microbiology, Department of Microbiology, Faculty of Science, Chulalongkorn University, Phayathai Road, Bangkok 10330 (Thailand); Pudhom, Khanitha [Department of Chemistry, Faculty of Science and Center for Petroleum, Petrochemicals and Advanced Materials, Chulalongkorn University, Phayathai Road, Bangkok 10330 (Thailand); Palaga, Tanapat, E-mail: tanapat.p@chula.ac.th [Graduate Program in Industrial Microbiology, Department of Microbiology, Faculty of Science, Chulalongkorn University, Phayathai Road, Bangkok 10330 (Thailand)

2011-11-18

Highlights: Black-Right-Pointing-Pointer A gedunin type limonoid from seeds of mangroves, 7-oxo-7-deacetoxygedunin, exhibits strong anti-osteoclastogenic activity. Black-Right-Pointing-Pointer Treatment with this limonoid results in significant decrease in expression of NFATc1 and osteoclast-related genes. Black-Right-Pointing-Pointer The mode of action of this limonoid is by inhibiting activation of the NF-{kappa}B and MAPK pathways which are activated by RANKL. -- Abstract: Osteoclasts together with osteoblasts play pivotal roles in bone remodeling. Aberrations in osteoclast differentiation and activity contribute to osteopenic disease. Osteoclasts differentiate from monocyte/macrophage progenitors, a process that is initiated by the interaction between receptor activator of NF-{kappa}B (RANK) and its ligand, RANKL. In this study, we identified 7-oxo-7-deacetoxygedunin (7-OG), a gedunin type limonoid from seeds of the mangrove Xylocarpus moluccensis, as a potent inhibitor of osteoclastogenesis. Additionally, 7-OG showed strong anti-osteoclastogenic activity with low cytotoxicity against the monocyte/macrophage progenitor cell line, RAW264.7. The IC50 for anti-osteoclastogenic activity was 4.14 {mu}M. Treatment with 7-OG completely abolished the appearance of multinucleated giant cells with tartrate-resistant acid phosphatase activity in RAW264.7 cells stimulated with RANKL. When the expression of genes related to osteoclastogenesis was investigated, a complete downregulation of NFATc1 and cathepsin K and a delayed downregulation of irf8 were observed upon 7-OG treatment in the presence of RANKL. Furthermore, treatment with this limonoid suppressed RANKL-induced activation of p38, MAPK and Erk and nuclear localization of NF-{kappa}B p65. Taken together, we present evidence indicating a plant limonoid as a novel osteoclastogenic inhibitor that could be used for osteoporosis and related conditions.

Dexamethasone protection from TNF-alpha-induced cell death in MCF-7 cells requires NF-kappaB and is independent from AKT

Directory of Open Access Journals (Sweden)

Mejía Salvador

2006-02-01

Full Text Available Abstract Background The biochemical bases for hormone dependence in breast cancer have been recognized as an important element in tumor resistance, proliferation and metastasis. On this respect, dexamethasone (Dex dependent protection against TNF-alpha-mediated cell death in the MCF-7 cell line has been demonstrated to be a useful model for the study of this type of cancer. Recently, cytoplasmic signaling induced by steroid receptors has been described, such as the activation of the PI3K/Akt and NF-kappaB pathways. We evaluated their possible participation in the Dex-dependent protection against TNF-alpha-mediated cell death. Results Cellular cultures of the MCF-7 cell line were exposed to either, TNF-alpha or TNF-alpha and Dex, and cell viability was evaluated. Next, negative dominants of PI3K and IkappaB-alpha, designed to block the PI3K/Akt and NF-kappaB pathways, respectively, were transfected and selection and evaluation of several clones overexpressing the mutants were examined. Also, correlation with inhibitor of apoptosis proteins (IAPs expression was examined. Independent inhibition of these two pathways allowed us to test their participation in Dex-dependent protection against TNF-alpha-cytotoxicity in MCF-7 cells. Expression of the PI3K dominant negative mutant did not alter the protection conferred by Dex against TNF-alpha mediated cell death. Contrariwise, clones expressing the IkappaB-alpha dominant negative mutant lost the Dex-conferred protection against TNF-alpha. In these clones degradation of c-IAP was accelerated, while that of XIAP was remained unaffected. Conclusion NF-kappaB, but not PI3K/Akt activation, is required for the Dex protective effect against TNF-alpha-mediated cell death, and correlates with lack of degradation of the anti-apoptotic protein c-IAP1.

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

Energy Technology Data Exchange (ETDEWEB)

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

2010-05-28

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

Mangiferin, a novel nuclear factor kappa B-inducing kinase inhibitor, suppresses metastasis and tumor growth in a mouse metastatic melanoma model

Energy Technology Data Exchange (ETDEWEB)

Takeda, Tomoya; Tsubaki, Masanobu; Sakamoto, Kotaro; Ichimura, Eri; Enomoto, Aya; Suzuki, Yuri [Division of Pharmacotherapy, Kinki University School of Pharmacy, Kowakae, Higashi-, Osaka (Japan); Itoh, Tatsuki [Department of Food Science and Nutrition, Kinki University School of Agriculture, Nara, Nara (Japan); Imano, Motohiro [Department of Surgery, Kinki University School of Medicine, Osakasayama, Osaka (Japan); Tanabe, Genzoh; Muraoka, Osamu [Laboratory of Pharmaceutical Organic Chemistry, School of Pharmacy, Kinki University, Kowakae, Higashi-, Osaka (Japan); Matsuda, Hideaki [Department of Natural Drugs Resources, Kinki University School of Pharmacy, Kowakae, Higashi-, Osaka (Japan); Satou, Takao [Department of Pathology, Kinki University School of Medicine, Osakasayama, Osaka (Japan); Nishida, Shozo, E-mail: nishida@phar.kindai.ac.jp [Division of Pharmacotherapy, Kinki University School of Pharmacy, Kowakae, Higashi-, Osaka (Japan)

2016-09-01

Advanced metastatic melanoma, one of the most aggressive malignancies, is currently without reliable therapy. Therefore, new therapies are urgently needed. Mangiferin is a naturally occurring glucosylxanthone and exerts many beneficial biological activities. However, the effect of mangiferin on metastasis and tumor growth of metastatic melanoma remains unclear. In this study, we evaluated the effect of mangiferin on metastasis and tumor growth in a mouse metastatic melanoma model. We found that mangiferin inhibited spontaneous metastasis and tumor growth. Furthermore, mangiferin suppressed the nuclear translocation of nuclear factor kappa B (NF-κB) and expression of phosphorylated NF-κB-inducing kinase (NIK), inhibitor of kappa B kinase (IKK), and inhibitor of kappa B (IκB) and increases the expression of IκB protein in vivo. In addition, we found that mangiferin inhibited the expression of matrix metalloproteinases (MMPs) and very late antigens (VLAs) in vivo. Mangiferin treatment also increased the expression of cleaved caspase-3, cleaved Poly ADP ribose polymerase-1 (PARP-1), p53 upregulated modulator of apoptosis (PUMA), p53, and phosphorylated p53 proteins, and decreased the expression of Survivin and Bcl-associated X (Bcl-xL) proteins in vivo. These results indicate that mangiferin selectivity suppresses the NF-κB pathway via inhibition of NIK activation, thereby inhibiting metastasis and tumor growth. Importantly, the number of reported NIK selective inhibitors is limited. Taken together, our data suggest that mangiferin may be a potential therapeutic agent with a new mechanism of targeting NIK for the treatment of metastatic melanoma. - Highlights: • Mangiferin prolongs survival in mice by inhibiting metastasis and tumor growth • Mangiferin selectivity suppresses the NF-κB pathway via inhibition of NIK activation • Mangiferin regulates the expression of MMPs, VLAs, and apoptosis regulatory proteins.

Dexamethasone protection from TNF-alpha-induced cell death in MCF-7 cells requires NF-kappaB and is independent from AKT.

Science.gov (United States)

Machuca, Catalina; Mendoza-Milla, Criselda; Córdova, Emilio; Mejía, Salvador; Covarrubias, Luis; Ventura, José; Zentella, Alejandro

2006-02-21

The biochemical bases for hormone dependence in breast cancer have been recognized as an important element in tumor resistance, proliferation and metastasis. On this respect, dexamethasone (Dex) dependent protection against TNF-alpha-mediated cell death in the MCF-7 cell line has been demonstrated to be a useful model for the study of this type of cancer. Recently, cytoplasmic signaling induced by steroid receptors has been described, such as the activation of the PI3K/Akt and NF-kappaB pathways. We evaluated their possible participation in the Dex-dependent protection against TNF-alpha-mediated cell death. Cellular cultures of the MCF-7 cell line were exposed to either, TNF-alpha or TNF-alpha and Dex, and cell viability was evaluated. Next, negative dominants of PI3K and IkappaB-alpha, designed to block the PI3K/Akt and NF-kappaB pathways, respectively, were transfected and selection and evaluation of several clones overexpressing the mutants were examined. Also, correlation with inhibitor of apoptosis proteins (IAPs) expression was examined. Independent inhibition of these two pathways allowed us to test their participation in Dex-dependent protection against TNF-alpha-cytotoxicity in MCF-7 cells. Expression of the PI3K dominant negative mutant did not alter the protection conferred by Dex against TNF-alpha mediated cell death. Contrariwise, clones expressing the IkappaB-alpha dominant negative mutant lost the Dex-conferred protection against TNF-alpha. In these clones degradation of c-IAP was accelerated, while that of XIAP was remained unaffected. NF-kappaB, but not PI3K/Akt activation, is required for the Dex protective effect against TNF-alpha-mediated cell death, and correlates with lack of degradation of the anti-apoptotic protein c-IAP1.

Anthropogenic Food Subsidy to a Commensal Carnivore: The Value and Supply of Human Faeces in the Diet of Free-Ranging Dogs

Directory of Open Access Journals (Sweden)

James R. A. Butler

2018-04-01

Full Text Available As the global population of free-ranging domestic dogs grows, there is increasing concern about impacts on human health and wildlife conservation. Effective management of dog populations requires reliable information on their diet, feeding behavior, and social ecology. Free-ranging dogs are reliant on humans, but anthropogenic food subsidies, particularly human faeces (i.e., coprophagy have not previously been fully quantified. In this study we assess the contributions of different food types to the diet, and their influences on the social behaviour of free-ranging dogs in communal lands of rural Zimbabwe, with a focus on coprophagy. Free-ranging dog diets, body condition, and sociology were studied amongst 72 dogs over 18 months using scat analysis and direct observations. Human faeces constituted the fourth most common item in scats (56% occurrence and contributed 21% by mass to the observed diet. Human faeces represented a valuable resource because relative to other food items it was consistently available, and of higher nutritional value than ‘sadza’ (maize porridge, the human staple and primary human-derived food, yielding 18.7% crude protein and 18.7 KJ/kg gross energy, compared to 8.3% and 18.5 KJ/kg for sadza, respectively. Human faeces had protein and energy values equivalent to mammal remains, another important food item. Dog condition was generally good, with 64% of adult females and 74% of adult males in the highest two body condition scores (on a five point scale, suggesting a plentiful and high quality food supply. Dogs largely fed alone, perhaps as a consequence of the small, inert, and spatially dispersed items that comprise their diet, and its abundance. We discuss the relationships between sanitation, human development, the supply of human faeces, female dog fertility, and population control.

DNA polymerase zeta cooperates with polymerases kappa and iota in translesion DNA synthesis across pyrimidine photodimers in cells from XPV patients.

Science.gov (United States)

Ziv, Omer; Geacintov, Nicholas; Nakajima, Satoshi; Yasui, Akira; Livneh, Zvi

2009-07-14

Human cells tolerate UV-induced cyclobutane pyrimidine dimers (CPD) by translesion DNA synthesis (TLS), carried out by DNA polymerase eta, the POLH gene product. A deficiency in DNA polymerase eta due to germ-line mutations in POLH causes the hereditary disease xeroderma pigmentosum variant (XPV), which is characterized by sunlight sensitivity and extreme predisposition to sunlight-induced skin cancer. XPV cells are UV hypermutable due to the activity of mutagenic TLS across CPD, which explains the cancer predisposition of the patients. However, the identity of the backup polymerase that carries out this mutagenic TLS was unclear. Here, we show that DNA polymerase zeta cooperates with DNA polymerases kappa and iota to carry out error-prone TLS across a TT CPD. Moreover, DNA polymerases zeta and kappa, but not iota, protect XPV cells against UV cytotoxicity, independently of nucleotide excision repair. This presents an extreme example of benefit-risk balance in the activity of TLS polymerases, which provide protection against UV cytotoxicity at the cost of increased mutagenic load.

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

Science.gov (United States)

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

1999-06-18

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

A Time for Change: The 42nd Annual Phi Delta Kappa/Gallup Poll of the Public's Attitudes toward the Public Schools

Science.gov (United States)

Bushaw, William J.; Lopez, Shane J.

2010-01-01

This is the latest in a series of polls sponsored by Phi Delta Kappa International with the Gallup Organization. The results of this year's poll are presented along with past results, when applicable, to give both a snapshot of Americans' opinions about their schools and an indication of how those opinions are changing over time. [Commentaries by…

Digital ranges of motion: normal values in young adults.

Science.gov (United States)

Mallon, W J; Brown, H R; Nunley, J A

1991-09-01

Analysis of the range of motion of fingers was done in young (eighteen to thirty-five year old) adult volunteers with no history of previous injury to their hands. The data show that there are slight differences between the individual digits. Notably, metacarpophalangeal flexion and total active motion increase linearly in proceeding from the index to the small finger. There were also minor differences in comparing sexes. Women have greater extension at the metacarpophalangeal joint in both active and passive motion and have a greater total active motion at all digits as a result. A significant tenodesis effect was found at the distal interphalangeal joint in normal subjects. No differences were found that could be attributable to handedness.

Polyethylenimine/kappa carrageenan: Micro-arc oxidation coating for passivation of magnesium alloy.

Science.gov (United States)

Golshirazi, A; Kharaziha, M; Golozar, M A

2017-07-01

The aim of this study was to combine micro-arc oxidation (MAO) and self-assembly technique to improve corrosion resistivity of AZ91 alloy. While a silicate-fluoride electrolyte was adopted for MAO treatment, polyethylenimine (PEI)/kappa carrageenan (KC) self-assembly coating was applied as the second coating layer. Resulted demonstrated the formation of forsterite-fluoride containing MAO coating on AZ91 alloy depending on the voltage and time of anodizing process. Addition of the second PEI/KC coating layer on MAO treated sample effectively enhanced the adhesive strength of MAO coated sample due to filling the pores with polymers and increase in the mechanical interlocking of coating to the substrate. Moreover, the corrosion evaluation considered by potentiodynamic polarization and electrochemical impedance spectroscopy confirmed that double layered PEI/KC:MAO coating presented superior resistance to corrosion attack. It is envisioned that the proposed double layered PEI/KC:MAO coating could be useful for biomedical applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Role of Genetic Variation Near Interferon-Kappa in Systemic Lupus Erythematosus

Directory of Open Access Journals (Sweden)

Isaac T. W. Harley

2010-01-01

Full Text Available Systemic lupus erythematosus (SLE is a systemic autoimmune disease characterized by increased type I interferons (IFNs and multiorgan inflammation frequently targeting the skin. IFN-kappa is a type I IFN expressed in skin. A pooled genome-wide scan implicated the IFNK locus in SLE susceptibility. We studied IFNK single nucleotide polymorphisms (SNPs in 3982 SLE cases and 4275 controls, composed of European (EA, African-American (AA, and Asian ancestry. rs12553951C was associated with SLE in EA males (odds ratio=1.93, P=2.5×10−4, but not females. Suggestive associations with skin phenotypes in EA and AA females were found, and these were also sex-specific. IFNK SNPs were associated with increased serum type I IFN in EA and AA SLE patients. Our data suggest a sex-dependent association between IFNK SNPs and SLE and skin phenotypes. The serum IFN association suggests that IFNK variants could influence type I IFN producing plasmacytoid dendritic cells in affected skin.

Density and speed of sound of lithium bromide with organic solvents: Measurement and correlation

Energy Technology Data Exchange (ETDEWEB)

Zafarani-Moattar, Mohammed Taghi [Department of Physical Chemistry, Faculty of Chemistry, University of Tabriz, Tabriz 51664 (Iran, Islamic Republic of); Research Institute of Fundamental Sciences, Tabriz 51664 (Iran, Islamic Republic of)], E-mail: zafarani47@yahoo.com; Shekaari, Hemayat [Department of Physical Chemistry, Faculty of Chemistry, University of Tabriz, Tabriz 51664 (Iran, Islamic Republic of); Research Institute of Fundamental Sciences, Tabriz 51664 (Iran, Islamic Republic of)

2007-12-15

Densities, {rho}, and speed of sound, u, of the solutions of LiBr with non-aqueous solvents (methanol, ethanol, 2-propanol, acetone, and acetonitrile) having a wide range of dielectric constants were measured at T = 298.15 K. Also, these measurements were made for the system (LiBr + N,N-dimethylacetamide) at T = 323.15 K. For the investigated systems, the limiting values for apparent molar volume, V{sub {phi}}{sup 0}, and the apparent molar isentropic compressibility, {kappa}{sub {phi}}{sup 0}, were obtained from the Redlich-Mayer and an abbreviated form of the Pitzer equations. The Pitzer and NRTL equations were satisfactorily used for the correlation of apparent molar volumes, V{sub {phi}}, and the apparent molar isentropic compressibility, {kappa}{sub {phi}}, values of the studied systems.

Effects of varied doses of psilocybin on time interval reproduction in human subjects.

Science.gov (United States)

Wackermann, Jirí; Wittmann, Marc; Hasler, Felix; Vollenweider, Franz X

2008-04-11

Action of a hallucinogenic substance, psilocybin, on internal time representation was investigated in two double-blind, placebo-controlled studies: Experiment 1 with 12 subjects and graded doses, and Experiment 2 with 9 subjects and a very low dose. The task consisted in repeated reproductions of time intervals in the range from 1.5 to 5s. The effects were assessed by parameter kappa of the 'dual klepsydra' model of internal time representation, fitted to individual response data and intra-individually normalized with respect to initial values. The estimates kappa were in the same order of magnitude as in earlier studies. In both experiments, kappa was significantly increased by psilocybin at 90 min from the drug intake, indicating a higher loss rate of the internal duration representation. These findings are tentatively linked to qualitative alterations of subjective time in altered states of consciousness.

Defining enthesitis in spondyloarthritis by ultrasound

DEFF Research Database (Denmark)

Terslev, Lene; Naredo, E; Iagnocco, A

2014-01-01

Objective: To standardize ultrasound (US) in enthesitis. Methods: An Initial Delphi exercise was undertaken to define US detected enthesitis and its core components. These definitions were subsequently tested on static images taken from Spondyloarthritis (SpA) patients in order to evaluate...... elementary component. On static images the intra-observer reliability showed a high degree of variability for the detection of elementary lesions with kappa coefficients ranging from 0.14 - 1. The inter-observer kappa value was variable with the lowest kappa for enthesophytes (0.24) and the best for Doppler...... activity at the enthesis (0.63). Conclusion: This is the first consensus based definition of US enthesitis and its elementary components and the first step performed to ensure a higher degree of homogeneity and comparability of results between studies and in daily clinical work. Defining Enthesitis...

Seismic b-values and its correlation with seismic moment and Bouguer gravity anomaly over Indo-Burma ranges of northeast India: Tectonic implications

Science.gov (United States)

Bora, Dipok K.; Borah, Kajaljyoti; Mahanta, Rinku; Borgohain, Jayanta Madhab

2018-03-01

b-value is one of the most significant seismic parameters for describing the seismicity of a given region at a definite time window. In this study, high-resolution map of the Gutenberg-Richter b-value, seismic moment-release, Bouguer gravity anomaly and fault-plane solutions containing faulting styles are analyzed in the Indo-Burma ranges of northeast India using the unified and homogeneous part of the seismicity record in the region (January 1964-December 2016). The study region is subdivided into few square grids of geographical window size 1° × 1° and b-values are calculated in each square grid. Our goal is to explore the spatial correlations and anomalous patterns between the b-value and parameters like seismic moment release, Bouguer gravity anomaly and faulting styles that can help us to better understand the seismotectonics and the state of present-day crustal stress within the Indo-Burma region. Most of the areas show an inverse correlation between b-value and seismic moment release as well as convergence rates. While estimating the b-value as a function of depth, a sudden increase of b-value at a depth of 50-60 km was found out and the receiver function modeling confirms that this depth corresponds to the crust-mantle transition beneath the study region. The region is also associated with negative Bouguer gravity anomalies and an inverse relation is found between Gravity anomaly and b-value. Comparing b-values with different faulting styles, reveal that the areas containing low b-values show thrust mechanism, while the areas associated with intermediate b-values show strike-slip mechanism. Those areas, where the events show thrust mechanism but containing a strike-slip component has the highest b-value.

Radiolysis studies of kappa carrageenan for bio based materials development

International Nuclear Information System (INIS)

Abad, Lucille V.

2010-01-01

Kappa (κ-) carrageenan oligomers are known to have several biological activities such as anti-HIV, anti-herpes, anti tumor and antioxidant properties. Recent progress in the development of radiation modified κ-carrageenan has resulted in new applications such as plant growth promoter, radiation dose indicator and hydrogels for wound dressing. This study would investigate on the changes in chemical structure, gelation and conformational transition behavior and molecular size of κ-carrageenan at doses from 0 to 200 kGy and would be correlated to these functions for the development of bio-based materials. Pulse radiolysis studies on κ-carrageenan was carried out to determine what transient species directly affects the degradation rate of κ-carrageenan in aqueous solution. The results reveal that there is no seeming reaction of the hydrated electron with κ-carrageenan. OH reacts with κ-carrageenan at a fast rate of approximately 1.2 x 10 9 M-1a-1. This value was influenced by conformational change from helix to coil by the addition of the metal ion Na +, reduction of molecular weight by the hydrolysis reaction and reduction of reactive sites by seasonally or irradiation. Most applications from the radiation degradation of polysaccharides started with the use of the ''hit and miss'' process where polysaccharides were irradiated at a certain dose range and finding out which dose is suitable for a specific function. Measurement of the radiation degradation yield (G d ) at different conditions can give an approximation of the Mw at an absorbed dose. This will allow the production of oligomers with a specified Mw. With the use of the G d both in solid and in aqueous solution, one can also make a rough calculation whether it is more economical to irradiateκ-carrageenan in solid r in aqueous solution. Results of this experiment reveal that the radiation yields (G d ) of κ-carrageenan in solid and in aqueous (1%) were as follows: 2.5, 1.7 and 1.2 x 10-7 mol J-1 for

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

Energy Technology Data Exchange (ETDEWEB)

Seong, Ah-Reum; Yoo, Jung-Yoon; Choi, KyungChul [Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, College of Medicine, Yonsei University, Seoul (Korea, Republic of); Lee, Mee-Hee [Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, College of Medicine, Yonsei University, Seoul (Korea, Republic of); Brain Korea 21 Project for Medical Sciences, Yonsei University, College of Medicine, Seoul (Korea, Republic of); Lee, Yoo-Hyun [Department of Food Science and Nutrition, The University of Suwon, Kyunggi-do (Korea, Republic of); Lee, Jeongmin [Department of Medical Nutrition, Kyung Hee University, Kyunggi-do (Korea, Republic of); Jun, Woojin [Department of Food and Nutrition, Chonnam National University, Gwangju (Korea, Republic of); Kim, Sunoh, E-mail: sunoh@korea.ac.kr [Jeollanamdo Institute of Natural Resources Research, Jeonnam (Korea, Republic of); Yoon, Ho-Geun, E-mail: yhgeun@yuhs.ac [Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, College of Medicine, Yonsei University, Seoul (Korea, Republic of); Brain Korea 21 Project for Medical Sciences, Yonsei University, College of Medicine, Seoul (Korea, Republic of)

2011-07-08

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

[Application study of qualitatively diagnosing prostate cancer using ultrahigh b-value DWI].

Science.gov (United States)

Ji, L B; Lu, Z H; Yao, H H; Cao, Y; Lu, W W; Qian, W X; Wang, X M; Hu, C H

2017-07-18

Objective: To explore the value of ultrahigh b-value DWI in diagnosis of prostate cancer. Methods: From October 2015 to October 2016, a total of 84 cases from Affiliated Changshu Hospital of Soochow University(39 cases of prostate cancer with a total of 57 lesions, 45 cases of benign prostate hyperplasia) were examined with T(2)WI, high b-value DWI (b=1 000 s/mm(2)) and ultrahigh b-value DWI (b=2 000 s/mm(2)) .Three image sets were rated respectively based on PI-RADS V2 by two radiologists and the scores were compared with biopsy results.The differences of the area under the ROC curve (AUC) among the three groups of each observer were compared by Z test. Results: The difference of AUC between ultrahigh b-value DWI and T(2)WI in the diagnosis of peripheral and transitional zone cancer was statistically significant between the two observers ( P =0.009 9, 0.008 2, 0.010 8 and 0.004 5 respectively), and there was no significant difference of AUC between ultrahigh b-value DWI and high b-value DWI in the diagnosis of peripheral and transitional zone cancer.The inter-reader agreement was found to be perfect for all lesions, peripheral zone lesions and transition zone lesions at ultrahigh b-value DWI ( kappa values were 0.738, 0.709 and 0.768 respectively). Conclusion: The diagnostic performance of ultrahigh b-value DWI is superior to high b-value DWI and T(2)WI in both peripheral zone and transition zone cancers.

Characterization and staging of central bile duct stenosis-Evaluation of the hepatocyte specific contrast agent gadoxetate disodium

Energy Technology Data Exchange (ETDEWEB)

Ringe, Kristina I., E-mail: ringe.kristina@mh-hannover.de [Hannover Medical School, Department of Diagnostic and Interventional Radiology, Carl-Neuberg Str. 1, 30625 Hannover (Germany); Ringe, Bastian P., E-mail: ringe.bastian@mh-hannover.de [Hannover Medical School, Department of General, Visceral and Transplantation Surgery, Carl-Neuberg Str. 1, 30625 Hannover (Germany); Bektas, Hueseyin, E-mail: bektas.hueseyin@mh-hannover.de [Hannover Medical School, Department of General, Visceral and Transplantation Surgery, Carl-Neuberg Str. 1, 30625 Hannover (Germany); Opherk, Jan P., E-mail: opherk.p@gmx.de [Hannover Medical School, Department of Diagnostic and Interventional Radiology, Carl-Neuberg Str. 1, 30625 Hannover (Germany); Reichelt, Angela, E-mail: reichelt.angela@mh-hannover.de [Hannover Medical School, Department of Diagnostic and Interventional Radiology, Carl-Neuberg Str. 1, 30625 Hannover (Germany); Lotz, Joachim, E-mail: joachim.lotz@med.uni-goettingen.de [Georg-August University Goettingen, Department of Diagnostic Radiology, Robert-Koch Str. 40, 37075 Goettingen (Germany); Wacker, Frank, E-mail: wacker.frank@mh-hannover.de [Hannover Medical School, Department of Diagnostic and Interventional Radiology, Carl-Neuberg Str. 1, 30625 Hannover (Germany); Meyer, Bernhard C., E-mail: meyer.bernhard@mh-hannover.de [Hannover Medical School, Department of Diagnostic and Interventional Radiology, Carl-Neuberg Str. 1, 30625 Hannover (Germany)

2012-11-15

Objective: To assess the value of gadoxetate disodium for characterization and staging of central bile duct stenosis (CBDS). Materials and methods: This prospective HIPAA-compliant study was IRB approved. 14 patients (8 male, 6 female; 36-80 years) with clinical suspicion of CBDS underwent preoperative MRI. To estimate the value of hepatocyte phase images (10, 20, 120 min p.i.), only T2w images (T2), only post-contrast images (CM), or both image datasets were assessed in three reading sessions by 3 readers. Agreement of each reading session with the intraoperative findings in terms of CBDS etiology and tumor extension (weighted kappa statistic) was calculated. Results: CBDS was caused by hilar cholangiocarcinoma (n = 9), gallbladder carcinoma (n = 4) and pancreatic carcinoma (n = 1). Characterization of CBDS etiology was correct by use of: T2w images in 57%, 64%, 50%; CM images in 64%, 57%, 50%; both in 71%, 64%, 64%. Agreement comparing reading sessions and intraoperative findings regarding tumor extension was fair up to moderate ({kappa}-range = 0.21-0.54) as a result of common underestimation. Interobserver agreement for tumor extension was fair ({kappa}-range = 0.31-0.33). Conclusions: By means of combined evaluation of T2 and CM images a more reliable characterization of CBDS was possible. Even though CBDS tended to be underestimated assessment of exact tumor extension was improved by contrast administration.

Hematology and serum chemistry reference ranges of free-ranging moose (Alces Alces) in Norway

OpenAIRE

Rostal, Melinda K.; Evans, Alina L.; Solberg, Erling L.; Arnemo, Jon Martin

2012-01-01

This article is also available here: http://www.jwildlifedis.org/ Baseline reference ranges of serum chemistry and hematology data can be important indicators for the status of both individuals or populations of wild animals that are affected by emerging pathogens, toxicants, or other causes of disease. Frequently, reference ranges for these values are not available for wildlife species or subspecies. We present hematologic and serum chemistry reference ranges for moose (Alces ...

Biological variation and reference intervals for circulating osteopontin, osteoprotegerin, total soluble receptor activator of nuclear factor kappa B ligand and high-sensitivity C-reactive protein

DEFF Research Database (Denmark)

Sennels, H P; Jacobsen, Søren; Jensen, T

2007-01-01

Objective. Monitoring inflammatory diseases and osteoclastogenesis with osteopontin (OPN), osteoprotegerin (OPG), total soluble receptor activator of nuclear factor kappa B ligand (total sRANKL) and high-sensitivity C-reactive protein (hsCRP) has recently attracted increased interest. The purpose...

Immunoglobulin kappa deleting element rearrangements in precursor-B acute lymphoblastic leukemia are stable targets for detection of minimal residual disease by real-time quantitative PCR

NARCIS (Netherlands)

van der Velden, V. H. J.; Willemse, M. J.; van der Schoot, C. E.; Hählen, K.; van Wering, E. R.; van Dongen, J. J. M.

2002-01-01

Immunoglobulin gene rearrangements are used as PCR targets for detection of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL). We Investigated the occurrence of monoclonal immunoglobulin kappa-deleting element (IGK-Kde) rearrangements by Southern blotting and PCR/heteroduplex

Firehose constraints of the bi-Kappa-distributed electrons: a zero-order approach for the suprathermal electrons in the solar wind

Czech Academy of Sciences Publication Activity Database

Lazar, M.; Shaaban, S. M.; Poedts, S.; Štverák, Štěpán

2017-01-01

Roč. 464, č. 1 (2017), s. 564-571 ISSN 0035-8711 Institutional support: RVO:68378289 Keywords : instabilities * plasmas * methods * analytical * methods: observational * solar wind Subject RIV: BL - Plasma and Gas Discharge Physics OBOR OECD: Fluids and plasma physics (including surface physics) Impact factor: 4.961, year: 2016 https://academic.oup.com/mnras/article-abstract/464/1/564/2236068/Firehose-constraints-of-the-bi-Kappa-distributed?redirectedFrom=fulltext

The bio-complex "reaction pattern in vertebrate cells" reduces cytokine-induced cellular adhesion molecule mRNA expression in human endothelial cells by attenuation of NF-kappaB translocation.

Science.gov (United States)

Rönnau, Cindy; Liebermann, Herbert E H; Helbig, Franz; Staudt, Alexander; Felix, Stephan B; Ewert, Ralf; Landsberger, Martin

2009-02-28

The bio-complex "reaction pattern in vertebrate cells" (RiV) is mainly represented by characteristic exosome-like particles--probably as reaction products of cells to specific stress. The transcription factor NF-kappaB plays a central role in inflammation. We tested the hypothesis that RiV particle preparations (RiV-PP) reduce cellular adhesion molecule (CAM) expression (ICAM-1, VCAM-1, E-selectin) by the attenuation of NF-kappaB translocation in human umbilical vein endothelial cells (HUVEC). After 4 hours, pre-incubation of HUVEC with RiV-PP before stimulation with TNF-alpha significantly reduced ICAM-1 (65.5+/-10.3%) and VCAM-1 (71.1+/-12.3%) mRNA expression compared to TNF-alpha-treated cells (100%, n=7). ICAM-1 surface expression was significantly albeit marginally reduced in RiV/TNF-alpha- treated cells (92.0+/-5.6%, n=4). No significant effect was observed on VCAM-1 surface expression. In RiV/TNF-alpha-treated cells (n=4), NF-kappaB subunits p50 (85.7+/-4.1%) and p65 (85.0+/-1.8%) nuclear translocation was significantly reduced. RiV-PP may exert an anti-inflammatory effect in HUVEC by reducing CAM mRNA expression via attenuation of p50 and p65 translocation.

Effects of various cone-beam computed tomography settings on the detection of recurrent caries under restorations in extracted primary teeth.

Science.gov (United States)

Kamburoğlu, Kıvanç; Sönmez, Gül; Berktaş, Zeynep Serap; Kurt, Hakan; Özen, Doĝukan

2017-06-01

The aim of this study was to assess the ex vivo diagnostic ability of 9 different cone-beam computed tomography (CBCT) settings in the detection of recurrent caries under amalgam restorations in primary teeth. Fifty-two primary teeth were used. Twenty-six teeth had dentine caries and 26 teeth did not have dentine caries. Black class II cavities were prepared and restored with amalgam. In the 26 carious teeth, recurrent caries were left under restorations. The other 26 intact teeth that did not have caries served as controls. Teeth were imaged using a 100×90-mm field of view and a 0.2-mm voxel size with 9 different CBCT settings. Four observers assessed the images using a 5-point scale. Kappa values were calculated to assess observer agreement. CBCT settings were compared with the gold standard using a receiver operating characteristic analysis. The area under the curve (AUC) values for each setting were compared using the chi-square test, with a significance level of α=.05. Intraobserver kappa values ranged from 0.366 to 0.664 for observer 1, from 0.311 to 0.447 for observer 2, from 0.597 to 1.000 for observer 3, and from 0.869 to 1 for observer 4. Furthermore, interobserver kappa values among the observers ranged from 0.133 to 0.814 for the first reading and from 0.197 to 0.805 for the second reading. The highest AUC values were found for setting 5 (0.5916) and setting 3 (0.5886), and were not found to be statistically significant ( P >.05). Variations in tube voltage and tube current did not affect the detection of recurrent caries under amalgam restorations in primary teeth.

Effects of various cone-beam computed tomography settings on the detection of recurrent caries under restorations in extracted primary teeth

Energy Technology Data Exchange (ETDEWEB)

Kamburoglu, Kivanc; Sonmez, Gul; Kurt, Hakan; Berktas, Zeynep Serap [Dept. of Dentomaxillofacial Radiology, Faculty of Dentistry, Ankara University, Ankara (Turkmenistan); Ozen, Dogukan [Dept. of Biostatistics, Faculty of Veterinary Medicine, Ankara University, Ankara (Turkmenistan)

2017-06-15

The aim of this study was to assess the ex vivo diagnostic ability of 9 different cone-beam computed tomography (CBCT) settings in the detection of recurrent caries under amalgam restorations in primary teeth. Fifty-two primary teeth were used. Twenty-six teeth had dentine caries and 26 teeth did not have dentine caries. Black class II cavities were prepared and restored with amalgam. In the 26 carious teeth, recurrent caries were left under restorations. The other 26 intact teeth that did not have caries served as controls. Teeth were imaged using a 100×90-mm field of view and a 0.2-mm voxel size with 9 different CBCT settings. Four observers assessed the images using a 5-point scale. Kappa values were calculated to assess observer agreement. CBCT settings were compared with the gold standard using a receiver operating characteristic analysis. The area under the curve (AUC) values for each setting were compared using the chi-square test, with a significance level of α=.05. Intraobserver kappa values ranged from 0.366 to 0.664 for observer 1, from 0.311 to 0.447 for observer 2, from 0.597 to 1.000 for observer 3, and from 0.869 to 1 for observer 4. Furthermore, interobserver kappa values among the observers ranged from 0.133 to 0.814 for the first reading and from 0.197 to 0.805 for the second reading. The highest AUC values were found for setting 5 (0.5916) and setting 3 (0.5886), and were not found to be statistically significant (P>.05). Variations in tube voltage and tube current did not affect the detection of recurrent caries under amalgam restorations in primary teeth.

Effects of various cone-beam computed tomography settings on the detection of recurrent caries under restorations in extracted primary teeth

International Nuclear Information System (INIS)

Kamburoglu, Kivanc; Sonmez, Gul; Kurt, Hakan; Berktas, Zeynep Serap; Ozen, Dogukan

2017-01-01

The aim of this study was to assess the ex vivo diagnostic ability of 9 different cone-beam computed tomography (CBCT) settings in the detection of recurrent caries under amalgam restorations in primary teeth. Fifty-two primary teeth were used. Twenty-six teeth had dentine caries and 26 teeth did not have dentine caries. Black class II cavities were prepared and restored with amalgam. In the 26 carious teeth, recurrent caries were left under restorations. The other 26 intact teeth that did not have caries served as controls. Teeth were imaged using a 100×90-mm field of view and a 0.2-mm voxel size with 9 different CBCT settings. Four observers assessed the images using a 5-point scale. Kappa values were calculated to assess observer agreement. CBCT settings were compared with the gold standard using a receiver operating characteristic analysis. The area under the curve (AUC) values for each setting were compared using the chi-square test, with a significance level of α=.05. Intraobserver kappa values ranged from 0.366 to 0.664 for observer 1, from 0.311 to 0.447 for observer 2, from 0.597 to 1.000 for observer 3, and from 0.869 to 1 for observer 4. Furthermore, interobserver kappa values among the observers ranged from 0.133 to 0.814 for the first reading and from 0.197 to 0.805 for the second reading. The highest AUC values were found for setting 5 (0.5916) and setting 3 (0.5886), and were not found to be statistically significant (P>.05). Variations in tube voltage and tube current did not affect the detection of recurrent caries under amalgam restorations in primary teeth

Validity and reliability of a method for assessment of cervical vertebral maturation.

Science.gov (United States)

Zhao, Xiao-Guang; Lin, Jiuxiang; Jiang, Jiu-Hui; Wang, Qingzhu; Ng, Sut Hong

2012-03-01

To evaluate the validity and reliability of the cervical vertebral maturation (CVM) method with a longitudinal sample. Eighty-six cephalograms from 18 subjects (5 males and 13 females) were selected from the longitudinal database. Total mandibular length was measured on each film; an increased rate served as the gold standard in examination of the validity of the CVM method. Eleven orthodontists, after receiving intensive training in the CVM method, evaluated all films twice. Kendall's W and the weighted kappa statistic were employed. Kendall's W values were higher than 0.8 at both times, indicating strong interobserver reproducibility, but interobserver agreement was documented twice at less than 50%. A wide range of intraobserver agreement was noted (40.7%-79.1%), and substantial intraobserver reproducibility was proved by kappa values (0.53-0.86). With regard to validity, moderate agreement was reported between the gold standard and observer staging at the initial time (kappa values 0.44-0.61). However, agreement seemed to be unacceptable for clinical use, especially in cervical stage 3 (26.8%). Even though the validity and reliability of the CVM method proved statistically acceptable, we suggest that many other growth indicators should be taken into consideration in evaluating adolescent skeletal maturation.

Improvement of mechanical properties of hydrogel by irradiation of polymers in aqueous solution with {kappa}-carrageenan

Energy Technology Data Exchange (ETDEWEB)

Makuuchi, K.; Yoshii, F. [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment; Aranilla, C.T. [Philippine Nuclear Research Institute, Diliman, Quezon (Philippines); Zhai, M. [Department of Technical Physics, Peking Univ., Beijing (China)

2000-03-01

Predominate radiation reaction of {kappa}-carrageenan (KC) hydrogel is the main chain scission of KC. The gel strength of KC hydrogel decreased with increasing irradiation dose. However, KC was found to enhances the radiation crosslinking of synthetic water-soluble polymer (SWSP) such as poly(ethylene oxide) (PEO) and poly(N-vinylpyrolidone) (PVP) in aqueous solution. The gel strength of SWSP hydrogel increased with increasing dose when KC was blended. Probably the radiation degraded KC radicals are recombined with radicals of PVP and PEO. The hydrogel thus prepared absorbs huge amounts of water due to the presence of strong hydrophilic -OSO{sub 3}{sup -} groups in KC. (author)

Reproducibility of multi-detector spiral computed tomography in detection of sub-segmental acute pulmonary embolism

International Nuclear Information System (INIS)

Brunot, S.; Corneloup, O.; Latrabe, V.; Montaudon, M.; Laurent, F.

2005-01-01

The aim of this study was to evaluate the inter-observer and intra-observer agreement of the diagnosis of sub-segmental acute pulmonary embolism (PE) in an inpatient population explored by 16 slice multi-detector spiral computed tomography (MDCT). Four hundred consecutive inpatients were referred for MDCT for the clinical suspicion of acute PE. One hundred and seventy seven (44.2%) had a known cardio-respiratory disease at the time of examination. Inter-observer and intra-observer agreements for the diagnosis of acute PE and of sub-segmental acute PE were assessed blind and independently by three experienced readers and by kappa statistics. Seventy-five patients were diagnosed as having acute PE findings (19.5%), and clots were located exclusively within sub-segmental arteries in nine patients (12%). When clots were limited to sub-segmental or more distal branches of the pulmonary arteries, kappa values were found to be moderate (0.56) to very good (0.85) for the diagnosis of sub-segmental acute PE, whereas for the diagnosis of acute PE in the whole population, kappa values ranged from 0.84 to 0.97. Intra-observer agreement was found to be perfect (kappa=1). MDCT is a reproducible technique for the diagnosis of sub-segmental acute PE as well as for acute PE. In this inpatient population, sub-segmental acute PE was not a rare event. (orig.)

Numerical Analysis of Turbulent Structures with a {kappa}-{epsilon} 3D Model of a Flow over a Cubic Obstacle; Estudio numerico de estructuras turbulentas con un modelo {kappa}-{epsilon} en 3D de un flujo sobre un obstaculo cubico

Energy Technology Data Exchange (ETDEWEB)

Millan Barrera, Cecia; Ramirez Leon, Hermilo [Instituto Mexicano de Tecnologia del Agua, Jiutepec, Morelos (Mexico)

2001-12-01

A numerical analysis is applied to a flow in an open channel and deformed by a three dimensional obstacle. The proposed model solves the 3-D Navier-Stokes equations, to which a {kappa}-{epsilon} turbulence model is coupled. The numerical analysis was constructed using a finite difference formulation for time evaluation purposed and staggered cells for space evaluation. The main goal of the present work was to study the turbulent structures and patterns of the flow due to an obstacle at the bottom of the channel plate. Our results are according to those found in the related literature. Flow patterns allow establishing the generation of turbulent structures by means of a comparison between this study and a most recent related work that evaluates the vorticity of the flow. [Spanish] Se reportan los resultados obtenidos, mediante simulaciones numericas, del movimiento del flujo en un canal con superficie libre y un obstaculo en el fondo. El sistema ecuaciones utilizado resuelve las ecuaciones de Navier-Stokes en tres dimensiones, al cual se le acoplo un modelo de turbulencia tipo {kappa}-{epsilon}. La solucion se obtiene numericamente utilizando un esquema en diferencias finitas para la evaluacion temporal de las variables y una celda escalonada para la evaluacion espacial de las mismas. El objetivo del modelo es estudiar los patrones de flujo y las estructuras turbulentas que se generan debido a la presencia del obstaculo. El estudio se realizo para un flujo en tres dimensiones. Los resultados son satisfactorios, ya que muestran concordancia con otros estudios numericos y experimentales encontrados en la literatura.

Extreme value distributions

CERN Document Server

Ahsanullah, Mohammad

2016-01-01

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.

Effect of the kappa-casein gene polymorphism, breed and seasonality on physicochemical characteristics, composition and stability of bovine milk Efeito do polimorfismo do gene da kappa-caseína, da raça e da sazonalidade sobre as características físico-químicas, de composição e de estabilidade do leite bovino

Directory of Open Access Journals (Sweden)

Bruno Garcia Botaro

2009-12-01

Full Text Available The objective of this study was to evaluate the effect of genetic polymorphism of kappa-casein, breed and seasonality on the physicochemical characteristics, composition and stability of milk in commercial dairy herds. A total of 879 milk and blood samples were collected from 603 Holstein and 276 Girolando cows, obtained during rainy and dry seasons. Milk samples were analyzed to determine the physicochemical characteristics, composition and ethanol stability, while blood samples were subjected to polymerase chain reaction to identify the kappa-casein genotype. The frequencies of genotypes AA, AB and BB of k-casein were respectively, 66.83, 31.84 and 1.33% for Holstein, and 71.38, 27.90 and 0.72% for the Girolando cows, respectively. The A allele was more frequent than the B allele, both for Holstein (0.827 and 0.173 and Girolando cows (0.853 and 0.147, respectively. Cows of AB and BB genotypes showed a higher milk fat content compared to the AA genotype. There was an interaction between breed and seasonality on the concentration of milk urea with higher values for Holstein and Girolando cows in the rainy and dry season, respectively. The levels of lactose, total solids, crude protein, true protein, casein and the casein:true protein ratio were higher during the dry season, while during the rainy season, the somatic cell count and milk urea concentration were higher. There was no association between milk stability and k-casein genotypes, but Holstein cows showed higher milk stability than Girolando cows, and milk was more stable during the rainy season than during the dry season.Objetivou-se avaliar o efeito do polimorfismo genético da kappa-caseína, da raça e da sazonalidade sobre as características físico-químicas, a composição e a estabilidade do leite bovino de rebanhos comerciais. Foram coletadas 879 amostras de leite e de sangue de 603 vacas da raça Holandesa e 276 da raça Girolando, obtidas durante as estações seca e chuvosa

Reactions of cisplatin with cysteine and methionine at constant pH; a computational study.

Science.gov (United States)

Zimmermann, Tomás; Burda, Jaroslav V

2010-02-07

Interactions of hydrated cisplatin complexes cis-[Pt(NH(3))(2)Cl(H(2)O)](+) and cis-[Pt(NH(3))(2)(OH)(H(2)O)](+) with cysteine and methionine in an aqueous solution at constant pH were explored using computational methods. Thermodynamic parameters of considered reactions were studied in a broad pH range, taking up to 4 protonation states of each molecule into account. Reaction free energies at constant pH were obtained from standard Gibbs free energies using the Legendre transformation. Solvation free energies and pK(a) values were calculated using the PCM model with UAHF cavities, recently adapted by us for transition metal complexes. The root mean square error of pK(a) values on a set of model platinum complexes and amino acids was equal to 0.74. At pH 7, the transformed Gibbs free energies differ by up to 15 kcal mol(-1) from the Gibbs free energies of model reactions with a constant number of protons. As for cysteine, calculations confirmed a strong preference for kappaS monodenate bonding in a broad pH range. The most stable product of the second reaction step, which proceeds from monodentate to chelate complex, is the kappa(2)S,N coordinated chelate. The reaction with methionine is more complex. In the first step all three considered methionine donor atoms (N, S and O) are thermodynamically preferred products depending on the platinum complex and the pH. This is in accordance with the experimental observation of a pH dependent migration between N and S donor atoms in a chemically related system. The most stable chelates of platinum with methionine are kappa(2)S,N and kappa(2)N,O bonded complexes. The comparison of reaction free energies of both amino acids suggests, that the bidentate methionine ligand can be displaced even by the monodentate cysteine ligand under certain conditions.

Laryngeal precursor lesions

DEFF Research Database (Denmark)

Mehlum, Camilla Slot; Larsen, Stine Rosenkilde; Kiss, Katalin

2018-01-01

; estimates of interrater and intrarater agreements were calculated with kappa statistics. Results: The crude intrarater agreements using the WHOC 2005 were 0.93 for rater 1 and 0.62 for rater 2. The corresponding unweighted kappa values were 0.90 (95% confidence interval [CI], 0.86-0.95) for rater 1 and 0.......43 (95% CI, 0.35-0.54) for rater 2, whereas the standard linear weighted kappa values were 0.93 (95% CI, 0.90-0.97) for rater 1 and 0.60 (95% CI, 0.53-0.69) for rater 2. The crude interrater agreement for the WHOC 2005 was 0.57, with a corresponding unweighted kappa value 0.38 (95% CI, 0...

Applying the Expectancy-Value Model to understand health values.

Science.gov (United States)

Zhang, Xu-Hao; Xie, Feng; Wee, Hwee-Lin; Thumboo, Julian; Li, Shu-Chuen

2008-03-01

Expectancy-Value Model (EVM) is the most structured model in psychology to predict attitudes by measuring attitudinal attributes (AAs) and relevant external variables. Because health value could be categorized as attitude, we aimed to apply EVM to explore its usefulness in explaining variances in health values and investigate underlying factors. Focus group discussion was carried out to identify the most common and significant AAs toward 5 different health states (coded as 11111, 11121, 21221, 32323, and 33333 in EuroQol Five-Dimension (EQ-5D) descriptive system). AAs were measured in a sum of multiplications of subjective probability (expectancy) and perceived value of attributes with 7-point Likert scales. Health values were measured using visual analog scales (VAS, range 0-1). External variables (age, sex, ethnicity, education, housing, marital status, and concurrent chronic diseases) were also incorporated into survey questionnaire distributed by convenience sampling among eligible respondents. Univariate analyses were used to identify external variables causing significant differences in VAS. Multiple linear regression model (MLR) and hierarchical regression model were used to investigate the explanatory power of AAs and possible significant external variable(s) separately or in combination, for each individual health state and a mixed scenario of five states, respectively. Four AAs were identified, namely, "worsening your quality of life in terms of health" (WQoL), "adding a burden to your family" (BTF), "making you less independent" (MLI) and "unable to work or study" (UWS). Data were analyzed based on 232 respondents (mean [SD] age: 27.7 [15.07] years, 49.1% female). Health values varied significantly across 5 health states, ranging from 0.12 (33333) to 0.97 (11111). With no significant external variables identified, EVM explained up to 62% of the variances in health values across 5 health states. The explanatory power of 4 AAs were found to be between 13

Reference values for electrooculography

International Nuclear Information System (INIS)

Barrientos Castanno, Alberto; Herrera Mora, Maritza; Garcia Baez, Obel

2012-01-01

Obtain electrooculographic reference values based on the patterns set by the Standardization Committee of the International Society for Clinical Electrophysiology of Vision (ISCEV). the lowest amplitude values of the potential ranged between 388 and 882 μv in the dark phase. The light peak was obtained between 9 and 10 minutes, and during this phase the potential reached an amplitude ranging between 808 and 1 963 μv. This amplitude variability may be related to the fact that the test was conducted without pupillary mydriasis. The reference value obtained for Arden index was 1,55 to 2,87

Prognosis Essay Scoring and Article Relevancy Using Multi-Text Features and Machine Learning

Directory of Open Access Journals (Sweden)

Arif Mehmood

2017-01-01

Full Text Available This study develops a model for essay scoring and article relevancy. Essay scoring is a costly process when we consider the time spent by an evaluator. It may lead to inequalities of the effort by various evaluators to apply the same evaluation criteria. Bibliometric research uses the evaluation criteria to find relevancy of articles instead. Researchers mostly face relevancy issues while searching articles. Therefore, they classify the articles manually. However, manual classification is burdensome due to time needed for evaluation. The proposed model performs automatic essay evaluation using multi-text features and ensemble machine learning. The proposed method is implemented in two data sets: a Kaggle short answer data set for essay scoring that includes four ranges of disciplines (Science, Biology, English, and English language Arts, and a bibliometric data set having IoT (Internet of Things and non-IoT classes. The efficacy of the model is measured against the Tandalla and AutoP approach using Cohen’s kappa. The model achieves kappa values of 0.80 and 0.83 for the first and second data sets, respectively. Kappa values show that the proposed model has better performance than those of earlier approaches.

Interobserver variability in interpretation of mammogram

International Nuclear Information System (INIS)

Lee, Kyung Jae; Lee, Hae Kyung; Lee, Won Chul; Hwang, In Young; Park, Young Gyu; Jung, Sang Seol; Kim, Hoon Kyo; Kim, Mi Hye; Kim, Hak Hee

2004-01-01

The purpose of this study was to evaluate the performance of radiologists for mammographic screening, and to analyze interobserver agreement in the interpretation of mammograms. 50 women were selected as subjects from the patients who were screened with mammograms at two university hospitals. The images were analyzed by five radiologists working independently and without their having any knowledge of the final diagnosis. The interobserver variation was analyzed by using the kappa statistic. There were moderate agreements for the findings of the parenchymal pattern (k=0.44; 95% CI 0.39-0.49). calcification type (k=0.66; 95% CI 0.60-0.72) and calcification distribution (K=0.43; 95% CI 0.38-0.48). The mean kappa values ranged from 0.66 to 0.42 for the mass findings. The mean kappa value for the final conclusion was 0.44 (95% CI 0.38-0.51). In general, moderate agreement was evident for all the categories that were evaluated. The general agreement was moderate, but there was wide variability in some findings. To improve the accuracy and reduce variability among physicians in interpretation, proper training of radiologists and standardization of criteria are essential for breast screening

Building Evidence of Validity: The Relation between Work Values, Interests, Personality, and Personal Values

Science.gov (United States)

Leuty, Melanie E.; Hansen, Jo-Ida C.

2013-01-01

The current study used work values components (WVC) to examine the relationship between work values, vocational interests, personality, and personal values. Most intercorrelations between work values and other constructs were in the small effect range. Overall correlations between scale scores provided evidence of convergent and discriminant…

Does the kappa opioid receptor system contribute to pain aversion?

Directory of Open Access Journals (Sweden)

Catherine M Cahill

2014-11-01

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.

Localizing value of pain distribution patterns in cervical spondylosis.

Science.gov (United States)

Bunyaratavej, Krishnapundha; Montriwiwatnchai, Peerapong; Siwanuwatn, Rungsak; Khaoroptham, Surachai

2015-04-01

Prospective observational study. To investigate the value of pain distribution in localizing appropriate surgical levels in patients with cervical spondylosis. Previous studies have investigated the value of pain drawings in its correlation with various features in degenerative spine diseases including surgical outcome, magnetic resonance imaging findings, discographic study, and psychogenic issues. However, there is no previous study on the value of pain drawings in identifying symptomatic levels for the surgery in cervical spondylosis. The study collected data from patients with cervical spondylosis who underwent surgical treatment between August 2009 and July 2012. Pain diagrams drawn separately by each patient and physician were collected. Pain distribution patterns among various levels of surgery were analyzed by the chi-square test. Agreement between different pairs of data, including pain diagrams drawn by each patient and physician, intra-examiner agreement on interpretation of pain diagrams, inter-examiner agreement on interpretation of pain diagrams, interpretation of pain diagram by examiners and actual surgery, was analyzed by Kappa statistics. The study group consisted of 19 men and 28 women with an average age of 55.2 years. Average duration of symptoms was 16.8 months. There was no difference in the pain distribution pattern at any level of surgery. The agreement between pain diagram drawn by each patient and physician was moderate. Intra-examiner agreement was moderate. There was slight agreement of inter-examiners, examiners versus actual surgery. Pain distribution pattern by itself has limited value in identifying surgical levels in patients with cervical spondylosis.

Kappa Group: The initial guess. A proposal in response to a commercial air transportation study

Science.gov (United States)

1991-01-01

Kappa Aerospace presents their Aeroworld Aircraft, the Initial Guess (IG). This aircraft is designed to generate profit in the market which is currently controlled by the train and boat industry. The main priority of the design team was to develop an extremely efficient aircraft that could be sold at a reasonable price. The IG offers a quick and safe alternative to the existing means of transportation at a competitive price. The cruise velocity of 28 ft/sec. allows all flights to be between 20 and 45 minutes, which is a remarkable savings in time compared to travel by boat or train. The IG is propelled by a single Astro-05 engine with a Zinger 10-6 propeller. The Astro-05 is not an extremely powerful engine; however, it provides enough thrust to meet the design and safety requirements. The major advantage of the Astro-05 is that it is the most efficient engine available. The fuel efficiency of the Astro-05 is what puts the aircraft ahead of the competition. The money saved on an efficient engine can be passed on as lower ticket prices or increased revenue. The IG has a payload of 56 passengers and a wingspan of 7 ft. The 7 ft. wingspan allows the aircraft to fit into the gates of all of the cities that are targeted. Future endeavors of Kappa Aerospace will include fitting a stretch version of the IG with a larger propulsion system. This derivative aircraft will be able to carry more passengers and will be placed on the routes which have the greatest demand for travel. The fuselage and empennage are made of a wooden truss configuration, while the wing is made of a rib/spare configuration. The stress carrying elements are made of spruce, the nonstress carrying elements are made of balsa. The wing is removable for easy access into the fuselage. The easy access to the batteries will keep maintenance costs down.

Ocean acidification weakens the immune response of blood clam through hampering the NF-kappa β and toll-like receptor pathways.

Science.gov (United States)

Liu, Saixi; Shi, Wei; Guo, Cheng; Zhao, Xinguo; Han, Yu; Peng, Chao; Chai, Xueliang; Liu, Guangxu

2016-07-01

The impact of pCO2 driven ocean acidification on marine bivalve immunity remains poorly understood. To date, this impact has only been investigated in a few bivalve species and the underlying molecular mechanism remains unknown. In the present study, the effects of the realistic future ocean pCO2 levels (pH at 8.1, 7.8, and 7.4) on the total number of haemocyte cells (THC), phagocytosis status, blood cell types composition, and expression levels of twelve genes from the NF-kappa β signaling and toll-like receptor pathways of a typical bottom burrowing bivalve, blood clam (Tegillarca granosa), were investigated. The results obtained showed that while both THC number and phagocytosis frequency were significantly reduced, the percentage of red and basophil granulocytes were significantly decreased and increased, respectively, upon exposure to elevated pCO2. In addition, exposure to pCO2 acidified seawater generally led to a significant down-regulation in the inducer and key response genes of NF-kappa β signaling and toll-like receptor pathways. The results of the present study revealed that ocean acidification may hamper immune responses of the bivalve T. granosa which subsequently render individuals more susceptible to pathogens attacks such as those from virus and bacteria. Copyright © 2016 Elsevier Ltd. All rights reserved.

Clinical application of the basic definition of malnutrition proposed by the European Society for Clinical Nutrition and Metabolism (ESPEN): Comparison with classical tools in geriatric care.

Science.gov (United States)

Sánchez-Rodríguez, Dolores; Annweiler, Cédric; Ronquillo-Moreno, Natalia; Tortosa-Rodríguez, Andrea; Guillén-Solà, Anna; Vázquez-Ibar, Olga; Escalada, Ferran; Muniesa, Josep M; Marco, Ester

Malnutrition is a prevalent condition related to adverse outcomes in older people. Our aim was to compare the diagnostic capacity of the malnutrition criteria of the European Society of Parenteral and Enteral Nutrition (ESPEN) with other classical diagnostic tools. Cohort study of 102 consecutive in-patients ≥70 years admitted for postacute rehabilitation. Patients were considered malnourished if their Mini-Nutritional Assessment-Short Form (MNA-SF) score was ≤11 and serum albumin <3 mg/dL or MNA-SF ≤ 11, serum albumin <3 mg/dL, and usual clinical signs and symptoms of malnutrition. Sensitivity, specificity, positive and negative predictive values, accuracy likelihood ratios, and kappa values were calculated for both methods: and compared with ESPEN consensus. Of 102 eligible in-patients, 88 fulfilled inclusion criteria and were identified as "at risk" by MNA-SF. Malnutrition diagnosis was confirmed in 11.6% and 10.5% of the patients using classical methods,whereas 19.3% were malnourished according to the ESPEN criteria. Combined with low albumin levels, the diagnosis showed 57.9% sensitivity, 64.5% specificity, 85.9% negative predictive value,0.63 accuracy (fair validity, low range), and kappa index of 0.163 (poor ESPEN agreement). The combination of MNA-SF, low albumin, and clinical malnutrition showed 52.6% sensitivity, 88.3% specificity, 88.3%negative predictive value, and 0.82 accuracy (fair validity, low range), and kappa index of 0.43 (fair ESPEN agreement). Malnutrition was almost twice as prevalent when diagnosed by the ESPEN consensus, compared to classical assessment methods: Classical methods: showed fair validity and poor agreement with the ESPEN consensus in assessing malnutrition in geriatric postacute care. Copyright © 2018 Elsevier B.V. All rights reserved.

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

Science.gov (United States)

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

2017-12-01

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

Estimated burden of cardiovascular disease and value-based price range for evolocumab in a high-risk, secondary-prevention population in the US payer context.

Science.gov (United States)

Toth, Peter P; Danese, Mark; Villa, Guillermo; Qian, Yi; Beaubrun, Anne; Lira, Armando; Jansen, Jeroen P

2017-06-01

To estimate real-world cardiovascular disease (CVD) burden and value-based price range of evolocumab for a US-context, high-risk, secondary-prevention population. Burden of CVD was assessed using the UK-based Clinical Practice Research Datalink (CPRD) in order to capture complete CV burden including CV mortality. Patients on standard of care (SOC; high-intensity statins) in CPRD were selected based on eligibility criteria of FOURIER, a phase 3 CV outcomes trial of evolocumab, and categorized into four cohorts: high-risk prevalent atherosclerotic CVD (ASCVD) cohort (n = 1448), acute coronary syndrome (ACS) (n = 602), ischemic stroke (IS) (n = 151), and heart failure (HF) (n = 291) incident cohorts. The value-based price range for evolocumab was assessed using a previously published economic model. The model incorporated CPRD CV event rates and considered CV event reduction rate ratios per 1 mmol/L reduction in low-density lipoprotein-cholesterol (LDL-C) from a meta-analysis of statin trials by the Cholesterol Treatment Trialists Collaboration (CTTC), i.e. CTTC relationship. Multiple-event rates of composite CV events (ACS, IS, or coronary revascularization) per 100 patient-years were 12.3 for the high-risk prevalent ASCVD cohort, and 25.7, 13.3, and 23.3, respectively, for incident ACS, IS, and HF cohorts. Approximately one-half (42%) of the high-risk ASCVD patients with a new CV event during follow-up had a subsequent CV event. Combining these real-world event rates and the CTTC relationship in the economic model, the value-based price range (credible interval) under a willingness-to-pay threshold of $150,000/quality-adjusted life-year gained for evolocumab was $11,990 ($9,341-$14,833) to $16,856 ($12,903-$20,678) in ASCVD patients with baseline LDL-C levels ≥70 mg/dL and ≥100 mg/dL, respectively. Real-world CVD burden is substantial. Using the observed CVD burden in CPRD and the CTTC relationship, the cost-effectiveness analysis showed

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)

2011-01-01

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

Interobserver and intraobserver reliability of two classification systems for intra-articular calcaneal fractures.

Science.gov (United States)

Lauder, Anthony J; Inda, David J; Bott, Aaron M; Clare, Michael P; Fitzgibbons, Timothy C; Mormino, Matthew A

2006-04-01

For a fracture classification to be useful it must provide prognostic significance, interobserver reliability, and intraobserver reproducibility. Most studies have found reliability and reproducibility to be poor for fracture classification schemes. The purpose of this study was to evaluate the interobserver and intraobserver reliability of the Sanders and Crosby-Fitzgibbons classification systems, two commonly used methods for classifying intra-articular calcaneal fractures. Twenty-five CT scans of intra-articular calcaneal fractures occurring at one trauma center were reviewed. The CT images were presented to eight observers (two orthopaedic surgery chief residents, two foot and ankle fellows, two fellowship-trained orthopaedic trauma surgeons, and two fellowship-trained foot and ankle surgeons) on two separate occasions 8 weeks apart. On each viewing, observers were asked to classify the fractures according to both the Sanders and Crosby-Fitzgibbons systems. Interobserver reliability and intraobserver reproducibility were assessed with computer-generated kappa statistics (SAS software; SAS Institute Inc., Cary, North Carolina). Total unanimity (eight of eight observers assigned the same fracture classification) was achieved only 24% (six of 25) of the time with the Sanders system and 36% (nine of 25) of the time with the Crosby-Fitzgibbons scheme. Interobserver reliability for the Sanders classification method reached a moderate (kappa = 0.48, 0.50) level of agreement, when the subclasses were included. The agreement level increased but remained in the moderate (kappa = 0.55, 0.55) range when the subclasses were excluded. Interobserver agreement reached a substantial (kappa = 0.63, 0.63) level with the Crosby-Fitzgibbons system. Intraobserver reproducibility was better for both schemes. The Sanders system with subclasses included reached moderate (kappa = 0.57) agreement, while ignoring the subclasses brought agreement into the substantial (kappa = 0.77) range

A survey of commercially available broilers marketed as organic, free-range, and conventional broilers for cooked meat yields, meat composition, and relative value.

Science.gov (United States)

Husak, R L; Sebranek, J G; Bregendahl, K

2008-11-01

The objective of this survey was to investigate qualitative and quantitative properties of meat from organic, free-range, and conventional broilers as currently provided to consumers. Fifteen broilers from 4 suppliers of each type were evaluated for raw meat yield, cooked meat yield, proximate composition, pH, color, lipid oxidation, fatty acid composition, and sensory attributes. Organic broilers yielded more dark (thigh) meat (P free-range or conventional, when compared on a raw-meat basis, but conventional and free-range broilers yielded more (P free-range or conventional. Organic breast and thigh meat was less yellow (P free-range or conventional. Fatty acid analysis showed that organic breasts and thighs were lower (P free-range and conventional broilers. Shear force measurements were less (P free-range and organic broilers. Sensory panel results indicated that thighs from conventional broilers were more tender (P free-range and organic broilers, whereas other sensory properties did not differ. At the time of the study, March through May of 2006, the average retail prices for US broilers were USD 3.19, USD 2.78, and USD 1.29 per pound (USD 7.03, USD 6.13, and USD 2.84/kg) for organic, free-range, and conventional, respectively. Whereas a difference in the fatty acid composition was the largest difference observed between retail broilers in this survey, it is important to note that diets and production environments within the study were not controlled. It is apparent that the market prices for broilers at the time of this study are not fully reflected in the quantitative and qualitative measurements included in this study. It appears that consumers may be placing significant value on more intangible attributes associated with broilers marketed as organic and free-range chicken than on those attributes measured in this study.

Norming a VALUE rubric to assess graduate information literacy skills.

Science.gov (United States)

Turbow, David J; Evener, Julie

2016-07-01

The study evaluated whether a modified version of the information literacy Valid Assessment of Learning in Undergraduate Education (VALUE) rubric would be useful for assessing the information literacy skills of graduate health sciences students. Through facilitated calibration workshops, an interdepartmental six-person team of librarians and faculty engaged in guided discussion about the meaning of the rubric criteria. They applied the rubric to score student work for a peer-review essay assignment in the "Information Literacy for Evidence-Based Practice" course. To determine inter-rater reliability, the raters participated in a follow-up exercise in which they independently applied the rubric to ten samples of work from a research project in the doctor of physical therapy program: the patient case report assignment. For the peer-review essay, a high level of consistency in scoring was achieved for the second workshop, with statistically significant intra-class correlation coefficients above 0.8 for 3 criteria: "Determine the extent of evidence needed," "Use evidence effectively to accomplish a specific purpose," and "Access the needed evidence." Participants concurred that the essay prompt and rubric criteria adequately discriminated the quality of student work for the peer-review essay assignment. When raters independently scored the patient case report assignment, inter-rater agreement was low and statistically insignificant for all rubric criteria (kappa=-0.16, p>0.05-kappa=0.12, p>0.05). While the peer-review essay assignment lent itself well to rubric calibration, scorers had a difficult time with the patient case report. Lack of familiarity among some raters with the specifics of the patient case report assignment and subject matter might have accounted for low inter-rater reliability. When norming, it is important to hold conversations about search strategies and expectations of performance. Overall, the authors found the rubric to be appropriate for

Modified Cut-Off Value of the Urine Protein-To-Creatinine Ratio Is Helpful for Identifying Patients at High Risk for Chronic Kidney Disease: Validation of the Revised Japanese Guideline.

Science.gov (United States)

Yamamoto, Hiroyuki; Yamamoto, Kyoko; Yoshida, Katsumi; Shindoh, Chiyohiko; Takeda, Kyoko; Monden, Masami; Izumo, Hiroko; Niinuma, Hiroyuki; Nishi, Yutaro; Niwa, Koichiro; Komatsu, Yasuhiro

2015-11-01

Chronic kidney disease (CKD) is a global public health issue, and strategies for its early detection and intervention are imperative. The latest Japanese CKD guideline recommends that patients without diabetes should be classified using the urine protein-to-creatinine ratio (PCR) instead of the urine albumin-to-creatinine ratio (ACR); however, no validation studies are available. This study aimed to validate the PCR-based CKD risk classification compared with the ACR-based classification and to explore more accurate classification methods. We analyzed two previously reported datasets that included diabetic and/or cardiovascular patients who were classified into early CKD stages. In total, 860 patients (131 diabetic patients and 729 cardiovascular patients, including 193 diabetic patients) were enrolled. We assessed the CKD risk classification of each patient according to the estimated glomerular filtration rate and the ACR-based or PCR-based classification. The use of the cut-off value recommended in the current guideline (PCR 0.15 g/g creatinine) resulted in risk misclassification rates of 26.0% and 16.6% for the two datasets. The misclassification was primarily caused by underestimation. Moderate to substantial agreement between each classification was achieved: Cohen's kappa, 0.56 (95% confidence interval, 0.45-0.69) and 0.72 (0.67-0.76) in each dataset, respectively. To improve the accuracy, we tested various candidate PCR cut-off values, showing that a PCR cut-off value of 0.08-0.10 g/g creatinine resulted in improvement in the misclassification rates and kappa values. Modification of the PCR cut-off value would improve its efficacy to identify high-risk populations who will benefit from early intervention.

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

Science.gov (United States)

Thorne, Richard M.; Summers, Danny

1991-01-01

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

Evaluation of color encodings for high dynamic range pixels

Science.gov (United States)

Boitard, Ronan; Mantiuk, Rafal K.; Pouli, Tania

2015-03-01

Traditional Low Dynamic Range (LDR) color spaces encode a small fraction of the visible color gamut, which does not encompass the range of colors produced on upcoming High Dynamic Range (HDR) displays. Future imaging systems will require encoding much wider color gamut and luminance range. Such wide color gamut can be represented using floating point HDR pixel values but those are inefficient to encode. They also lack perceptual uniformity of the luminance and color distribution, which is provided (in approximation) by most LDR color spaces. Therefore, there is a need to devise an efficient, perceptually uniform and integer valued representation for high dynamic range pixel values. In this paper we evaluate several methods for encoding colour HDR pixel values, in particular for use in image and video compression. Unlike other studies we test both luminance and color difference encoding in a rigorous 4AFC threshold experiments to determine the minimum bit-depth required. Results show that the Perceptual Quantizer (PQ) encoding provides the best perceptual uniformity in the considered luminance range, however the gain in bit-depth is rather modest. More significant difference can be observed between color difference encoding schemes, from which YDuDv encoding seems to be the most efficient.

Laboratory Studies of the Reactive Chemistry and Changing CCN Properties of Secondary Organic Aerosol, Including Model Development

Energy Technology Data Exchange (ETDEWEB)

Scot Martin

2013-01-31

The chemical evolution of secondary-organic-aerosol (SOA) particles and how this evolution alters their cloud-nucleating properties were studied. Simplified forms of full Koehler theory were targeted, specifically forms that contain only those aspects essential to describing the laboratory observations, because of the requirement to minimize computational burden for use in integrated climate and chemistry models. The associated data analysis and interpretation have therefore focused on model development in the framework of modified kappa-Koehler theory. Kappa is a single parameter describing effective hygroscopicity, grouping together several separate physicochemical parameters (e.g., molar volume, surface tension, and van't Hoff factor) that otherwise must be tracked and evaluated in an iterative full-Koehler equation in a large-scale model. A major finding of the project was that secondary organic materials produced by the oxidation of a range of biogenic volatile organic compounds for diverse conditions have kappa values bracketed in the range of 0.10 +/- 0.05. In these same experiments, somewhat incongruently there was significant chemical variation in the secondary organic material, especially oxidation state, as was indicated by changes in the particle mass spectra. Taken together, these findings then support the use of kappa as a simplified yet accurate general parameter to represent the CCN activation of secondary organic material in large-scale atmospheric and climate models, thereby greatly reducing the computational burden while simultaneously including the most recent mechanistic findings of laboratory studies.

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

International Nuclear Information System (INIS)

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

2011-01-01

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

Online Sorted Range Reporting

DEFF Research Database (Denmark)

Brodal, Gerth Stølting; Fagerberg, Rolf; Greve, Mark

2009-01-01

is motivated by (and is a generalization of) a problem with applications in search engines: On a tree where leaves have associated rank values, report the highest ranked leaves in a given subtree. Finally, the problem studied generalizes the classic range minimum query (RMQ) problem on arrays....

Range Selection and Median

DEFF Research Database (Denmark)

Jørgensen, Allan Grønlund; Larsen, Kasper Green

2011-01-01

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...

Renin-angiotensin system inhibition ameliorates CCl4-induced liver fibrosis in mice through the inactivation of nuclear transcription factor kappa B.

Science.gov (United States)

Saber, Sameh; Mahmoud, Amr A A; Helal, Noha S; El-Ahwany, Eman; Abdelghany, Rasha H

2018-06-01

Therapeutic interventions for liver fibrosis are still limited due to the complicated molecular pathogenesis. Renin-angiotensin system (RAS) seems to contribute to the development of hepatic fibrosis. Therefore, we aimed to examine the effect of RAS inhibition on CCl 4 -induced liver fibrosis. Mice were treated with silymarin (30 mg·kg -1 ), perindopril (1 mg·kg -1 ), fosinopril (2 mg·kg -1 ), or losartan (10 mg·kg -1 ). The administration of RAS inhibitors improved liver histology and decreased protein expression of alpha smooth muscle actin (α-SMA) and hepatic content of hydroxyproline. These effects found to be mediated via inactivation of nuclear transcription factor kappa B (NFκB) pathway by the inhibition of NFκB p65 phosphorylation at the Ser536 residue and phosphorylation-induced degradation of nuclear factor kappa-B inhibitor alpha (NFκBia) subsequently inhibited NFκB-induced TNF-α and TGF-β1, leading to lower levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) and vascular endothelial growth factor (VEGF). We concluded that the tissue affinity of the angiotensin converting enzyme inhibitors (ACEIs) has no impact on its antifibrotic activity and that interfering the RAS either through the inhibition of ACE or the blockade of AT1R has the same therapeutic benefit. These results suggest RAS inhibitors as promising candidates for further clinical trials in the management of hepatic fibrosis.

Estimating Time-Varying PCB Exposures Using Person-Specific Predictions to Supplement Measured Values: A Comparison of Observed and Predicted Values in Two Cohorts of Norwegian Women

Science.gov (United States)

Nøst, Therese Haugdahl; Breivik, Knut; Wania, Frank; Rylander, Charlotta; Odland, Jon Øyvind; Sandanger, Torkjel Manning

2015-01-01

Background Studies on the health effects of polychlorinated biphenyls (PCBs) call for an understanding of past and present human exposure. Time-resolved mechanistic models may supplement information on concentrations in individuals obtained from measurements and/or statistical approaches if they can be shown to reproduce empirical data. Objectives Here, we evaluated the capability of one such mechanistic model to reproduce measured PCB concentrations in individual Norwegian women. We also assessed individual life-course concentrations. Methods Concentrations of four PCB congeners in pregnant (n = 310, sampled in 2007–2009) and postmenopausal (n = 244, 2005) women were compared with person-specific predictions obtained using CoZMoMAN, an emission-based environmental fate and human food-chain bioaccumulation model. Person-specific predictions were also made using statistical regression models including dietary and lifestyle variables and concentrations. Results CoZMoMAN accurately reproduced medians and ranges of measured concentrations in the two study groups. Furthermore, rank correlations between measurements and predictions from both CoZMoMAN and regression analyses were strong (Spearman’s r > 0.67). Precision in quartile assignments from predictions was strong overall as evaluated by weighted Cohen’s kappa (> 0.6). Simulations indicated large inter-individual differences in concentrations experienced in the past. Conclusions The mechanistic model reproduced all measurements of PCB concentrations within a factor of 10, and subject ranking and quartile assignments were overall largely consistent, although they were weak within each study group. Contamination histories for individuals predicted by CoZMoMAN revealed variation between study subjects, particularly in the timing of peak concentrations. Mechanistic models can provide individual PCB exposure metrics that could serve as valuable supplements to measurements. Citation Nøst TH, Breivik K, Wania F

Dual formulation of covariant nonlinear duality-symmetric action of kappa-symmetric D3-brane

Science.gov (United States)

Vanichchapongjaroen, Pichet

2018-02-01

We study the construction of covariant nonlinear duality-symmetric actions in dual formulation. Essentially, the construction is the PST-covariantisation and nonlinearisation of Zwanziger action. The covariantisation made use of three auxiliary scalar fields. Apart from these, the construction proceed in a similar way to that of the standard formulation. For example, the theories can be extended to include interactions with external fields, and that the theories possess two local PST symmetries. We then explicitly demonstrate the construction of covariant nonlinear duality-symmetric actions in dual formulation of DBI theory, and D3-brane. For each of these theories, the twisted selfduality condition obtained from duality-symmetric actions are explicitly shown to match with the duality relation between field strength and its dual from the one-potential actions. Their on-shell actions between the duality-symmetric and the one-potential versions are also shown to match. We also explicitly prove kappa-symmetry of the covariant nonlinear duality-symmetric D3-brane action in dual formulation.

Comparative study of action of cell wall proteinases from various strains of Streptococcus cremoris on bovine α/sub s1-/, β-, and kappa-casein

International Nuclear Information System (INIS)

Visser, S.; Exterkate, F.A.; Slangen, C.J.; de Veer, G.J.C.M.

1986-01-01

Experiments are described in which partially purified cell wall proteinases of eight strains of S. cremoris, including strain HP, were compared in their action on α/sub s1 - /, β-, and kappa-casein, as visualized by starch gel electrophoresis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and TLC, and also in their action on methyl- 14 C-labeled β-casein

Caractérisation des processus d'ubiquitination régulant le facteur de transcription NF-kappaB au cours de l’activation lymphocytaire Rôle de l’E3 ligase TRIM13 et de la déubiquitinase USP34

OpenAIRE

Hatchi , Emeline

2014-01-01

The transcription factor NF-KappaB plays a critical role in the development, homeostasis, the survival of the immune system, but also in the propagation of certain lymphomas. The optimal activation of NF-KappaB in response to the engagement of many immunoreceptors rely on the implementation of large signalosomes where specific adaptors are recruited and poly-Ubiquitinylated in a non-Degradative manner. In response to proinflammatory cytokines or activation of antigen receptors, these Ubiquiti...

Hardware test program for evaluation of baseline range-range rate sensor concept

Science.gov (United States)

1985-01-01

The baseline range/range rate sensor concept was evaluated. The Interrupted CW (ICW) mode of operation continued with emphasis on establishing the sensitivity of the video portion of the receiver was 7 dB less than the theoretical value. This departs from test results of previous implementations in which achieved sensitivity was within 1.5 to 2 dB of the theoretical value. Several potential causes of this discrepancy in performance were identified and are scheduled for further investigation. Results indicate that a cost savings in both per unit and program costs are realizable by eliminating one of the modes of operation. An acquisition (total program) cost savings of approximately 10% is projected by eliminating the CW mode of operation. The modified R/R sensor would operate in the ICW mode only and would provide coverage from initial acquisition at 12 nmi to within a few hundred feet of the OMV. If the ICW mode only were selected, then an accompanying sensor would be required to provide coverage from a few hundred feet to docking.

Nonlinear Korteweg-de Vries-Burger equation for ion-acoustic shock waves in the presence of kappa distributed electrons and positrons

International Nuclear Information System (INIS)

Shah, Asif; Saeed, R

2011-01-01

The ion-acoustic shock waves are studied in electron-positron-ion plasma. The plasma system is composed of three components, specifically relativistic adiabatic ions, kappa distributed electrons and positrons. The Korteweg-de Vries-Burger equation is derived, solved analytically. The effects of plasma parameters on the shock strength and steepness are investigated. The numerical results are presented graphically for illustration. The results may have importance in non-thermal and relativistic plasmas of pulsar magnetosphere (Arons 2009 Astrophys. Space Sci. Library 357 373; Blasi and Amato arXiv:1007.4745V1 [astro-Ph.HE]).

[Multiple myeloma (IgG-kappa) infiltrating central nervous system, lymph nodes, liver, and kidneys, and with elevation of IgE].

Science.gov (United States)

Toyota, Shigeo; Nakamura, Norihiko; Dan, Kazuo

2004-05-01

A 63-year-old man was admitted because of general malaise, fever, headache, generalized lymphadenopathy and hepatomegaly in July 2002. He was diagnosed as having multiple myeloma (MM) (IgG-kappa type) with atypical plasma cells in the bone marrow, lymph nodes and cerebrospinal fluid. Systemic and intrathecal chemotherapy were effective. Because of an increase of polyclonal IgE, electrophoretic patterns revealed an M-peak which was not as sharp as that in IgG myeloma. IgE production is not impaired by the pathologic process in MM patients.

Dealing with missing data in a multi-question depression scale: a comparison of imputation methods

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Stuart Heather

2006-12-01

Full Text Available Abstract Background Missing data present a challenge to many research projects. The problem is often pronounced in studies utilizing self-report scales, and literature addressing different strategies for dealing with missing data in such circumstances is scarce. The objective of this study was to compare six different imputation techniques for dealing with missing data in the Zung Self-reported Depression scale (SDS. Methods 1580 participants from a surgical outcomes study completed the SDS. The SDS is a 20 question scale that respondents complete by circling a value of 1 to 4 for each question. The sum of the responses is calculated and respondents are classified as exhibiting depressive symptoms when their total score is over 40. Missing values were simulated by randomly selecting questions whose values were then deleted (a missing completely at random simulation. Additionally, a missing at random and missing not at random simulation were completed. Six imputation methods were then considered; 1 multiple imputation, 2 single regression, 3 individual mean, 4 overall mean, 5 participant's preceding response, and 6 random selection of a value from 1 to 4. For each method, the imputed mean SDS score and standard deviation were compared to the population statistics. The Spearman correlation coefficient, percent misclassified and the Kappa statistic were also calculated. Results When 10% of values are missing, all the imputation methods except random selection produce Kappa statistics greater than 0.80 indicating 'near perfect' agreement. MI produces the most valid imputed values with a high Kappa statistic (0.89, although both single regression and individual mean imputation also produced favorable results. As the percent of missing information increased to 30%, or when unbalanced missing data were introduced, MI maintained a high Kappa statistic. The individual mean and single regression method produced Kappas in the 'substantial agreement' range

Epidemiological reference ranges for low-density lipoprotein ...

African Journals Online (AJOL)

Although there is widespread acceptance that total cholesterol (TC) value reference ranges should be based on epidemiological rather than statistical considerations, the epidemiological action limits for Iow-density lipoprotein cholesterol (LDL-C) are still incomplete and only statistical reference ranges for apolipoprotein B ...

Sphingosine 1-phosphate-induced ICAM-1 expression via NADPH oxidase/ROS-dependent NF-kappaB cascade on human pulmonary alveolar epithelial cells

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Chin-Chung eLin

2016-03-01

Full Text Available The intercellular adhesion molecule-1 (ICAM-1 expression is frequently correlated with the lung inflammation. A bioactive sphingolipid metabolite, sphingosine-1-phosphate (S1P, was involved in inflammation through the adhesion molecules induction, and then caused lung injury. However, the transduction mechanisms of the S1P stimulation to induce ICAM-1 expression in human pulmonary alveolar epithelial cells (HPAEpiCs remain unclear. Here, we demonstrated that exposure of HPAEpiCs to S1P significantly induces ICAM-1 expression leading to increase monocyte adhesion on the surface of HPAEpiCs. These phenomena were effectively attenuated by pretreatments with series of inhibitors such as Rottlerin (PKCdelta, PF431396 (PYK2, diphenyleneiodonium chloride (DPI, apocynin (NADPH oxidase, Edaravone (ROS, and Bay11-7082 (NF-kappaB. Consistently, knockdown with siRNA transfection of PKCdelta, PYK2, p47phox, and p65 exhibited the same results. Pretreatment with both Gq-coupled receptor antagonist (GPA2A and Gi/o-coupled receptor antagonist (GPA2 also blocked S1P-induced ICAM-1 protein and mRNA expression. We observed that S1P induced PYK2 activation via a Gq-coupled receptor/PKCdelta-dependent pathway. In addition, S1P induced NADPH oxidase activation and intracellular ROS generation, which were also reduced by Rottlerin or PF431396. We demonstrated that S1P induced NF-kappaB p65 phosphorylation and translocation from the cytosol to the nucleus in HPAEpiCs, which was inhibited by Rottlerin, PF431396, APO, DPI, or Edaravone. In the in vitro study, we established that S1P induced monocyte adhesion via an ICAM-1-dependent pathway. In the in vivo study, we found that S1P induced ICAM-1 protein and mRNA levels in the lung fractions, pulmonary hematoma, and leukocyte (mainly eosinophils and neutrophils count in bronchoalveolar lavage (BAL fluid in mice via a PKCdelta/PYK2/NADPH oxidase/ROS/NF-kappaB signaling pathway. We concluded that S1P may induce lung

A novel electrochemical approach for nuclear factor kappa B detection based on triplex DNA and gold nanoparticles

International Nuclear Information System (INIS)

Shen Min; Yang Mei; Li Hao; Liang Zhiqiang; Li Genxi

2012-01-01

Highlights: ► A simple, selective, and sensitive electrochemical NF-κB sensor was presented. ► NF-κB was precisely qualified by chronocoulometry with a detection limit of 0.13 nM. ► NF-κB was also successfully detected in contaminated samples by our approach. - Abstract: The transcription factor nuclear factor kappa B (NF-κB) is always a standard for inducible transcription factors, while nearly all NF-κB studies require the measurement of the level of activated NF-κB in cells. Herein we report a novel electrochemical approach for accurate detection of NF-κB with the help of triplex DNA and gold nanoparticles (AuNPs). Firstly, double-stranded DNA (dsDNA) molecules are self-assembled on the surface of a gold electrode. Then, AuNPs are functionalized with triplex-forming oligonucleotide (TFO). Since TFO may act with the dsDNA to form triplex DNA, the TFO functionalized on the AuNPs surfaces will bind with the dsDNA immobilized on the electrode surface, bringing large amounts of electrochemical compounds [Ru(NH 3 ) 6 ] 3+ close to the electrode to generate an intense electrochemical signal. However, in the presence of NF-κB, the protein will capture and bind with the dsDNA to replace TFO–AuNPs, resulting in significant decrease of electrochemical signal of [Ru(NH 3 ) 6 ] 3+ . By using this “on-off” strategy, NF-κB has been quantified in the range from 0.4 to 12.0 nM, with a detection limit of 0.13 nM. This approach has also been successfully used to detect NF-κB in contaminated samples with high specificity.

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

2010-01-01

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...... investigated the effects of diets supplemented with apple, blackcurrant, or cherries on lipopolysaccharide (LPS)-induced NF-B activation in transgenic NF-B-luciferase mice. Whole body and organ specific NF-B activities were determined. The mice had ad libitum access to the respective experimental diets for 7...... slightly higher whole-body NF-B activation at 4 h, and all 3 experimental groups had higher NF-B activation at 6 h. LPS-induced NF-B activation in liver was increased with all 3 experimental diets, but no effects were observed in other organs. Our findings indicate that high intakes of lyophilized fruits...

Hematology and serum chemistry reference ranges of free-ranging moose (Alces alces) in Norway.

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Rostal, Melinda K; Evans, Alina L; Solberg, Erling J; Arnemo, Jon M

2012-07-01

Baseline reference ranges of serum chemistry and hematology data can be important indicators for the status of both individuals or populations of wild animals that are affected by emerging pathogens, toxicants, or other causes of disease. Frequently, reference ranges for these values are not available for wildlife species or subspecies. We present hematologic and serum chemistry reference ranges for moose (Alces alces) adults, yearlings, and calves in Norway sampled from 1992-2000. Additionally, we demonstrated that both induction time and chase time were correlated with initial rectal temperature, although they were not significantly correlated with cortisol, aspartate aminotransferase, glucose, or creatine kinase. Overall, the reference ranges given here are similar to those given for American moose, with a few differences that can be attributed to environment, testing methodology, or subspecies or species status. This is the first report, to our knowledge, of reference ranges for moose in Norway.

Intra- and inter-rater reliability of 3D passive intervertebral motion in subjects with nonspecific neck pain assessed by physical therapy students: A pilot study.

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Rossettini, Giacomo; Rondoni, Angie; Lovato, Tommaso; Strobe, Marco; Verzè, Elisa; Vicentini, Marco; Testa, Marco

2016-06-03

Passive Intervertebral Movements (PIVMs) are commonly used to assess and treat patients with nonspecific neck pain. Only very few studies have investigated 3D movements until now. This study assessed intra- and inter-rater reliability of three-dimensional (3D) cervical PIVMs performed by physical therapy students in patients with nonspecific neck pain. Thirty-one patients, mean age 47.2 ± 7.2 years, were independently evaluated by 2 physical therapy students. The raters (A and B) assessed mobility, end-feel and pain provocation performing bilaterally the 3D cervical segmental side-bending test (3D CSSB) from levels C2-C3 to C6-C7. Percentage agreement (raw, positive and negative), Cohen's kappa (95% CI), prevalence index and bias index were calculated to estimate intra- and inter-reliability. Intra-rater reliability showed kappa values ranging between fair and substantial (k 0.29-0.80) for pain provocation, mobility and end-feel, with percentage agreements between 61%-90%. Inter-rater reliability presented kappa values ranging between fair and substantial (k 0.22-0.62) for pain provocation, mobility and end-feel, with percentage agreements between 61% and 80%. Intra-rater reliability of 3D PIVMs was superior to inter-rater reliability in patients with nonspecific neck pain. The most repeatable evaluation parameter was pain. However overall poor reliability suggests avoiding the use of these techniques alone to examine patients and measure their outcome. Further studies are needed to investigate PIVMs reliability in combination with other assessment procedure in symptomatic patients.

Psychometric properties of the Swedish version of the Self-Transcendence Scale among very old people.

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Lundman, Berit; Årestedt, Kristofer; Norberg, Astrid; Norberg, Catharina; Fischer, Regina Santamäki; Lövheim, Hugo

2015-01-01

This study tested the psychometric properties of a Swedish version of the Self-Transcendence Scale (STS). Cohen's weighted kappa, agreement, absolute reliability, relative reliability, and internal consistency were calculated, and the underlying structure of the STS was established by exploratory factor analysis. There were 2 samples available: 1 including 194 people aged 85-103 years and a convenience sample of 60 people aged 21-69 years. Weighted kappa values ranged from .40 to .89. The intraclass correlation coefficient for the original STS was .763, and the least significant change between repeated tests was 6.25 points. The revised STS was found to have satisfactory psychometric properties, and 2 of the 4 underlying dimensions in Reed's self-transcendence theory were supported.

EFECTO DE LA ADICIÓN DE CARRAGENINA KAPPA I.II Y GOMA TARA SOBRE CARACTERÍSTICAS DE CALIDAD DEL JAMÓN DE CERDO PICADO Y COCIDO EFFECT OF THE ADDITION OF KAPPA I.II CARRAGEENAN AND TARA GUM ON QUALITY CHARACTERISTICS OF COOKED AND CHOPPED PORK HAMS

OpenAIRE

Diego Alonso Restrepo Molina; Fabio Alexander Molina Cote; Kenneth Roy Cabrera Torres

2010-01-01

Se evaluaron sinéresis, color y dureza instrumental y, sensorialmente las características de olor, sabor, color y dureza en jamones inyectados, cocidos y picados de cerdo, los cuales se habían elaborado aplicando en la salmuera de inyección una mezcla de hidrocoloides compuesta por carragenina kappa I.II y goma tara en una proporción de 79:21, en niveles del 1% y 1,2%, usando tres repeticiones para el estudio. Los jamones así elaborados se compararon contra un jamón testigo, elaborado sin el ...

Energy dependence of the zero-range DWBA normalization of the /sup 58/Ni(/sup 3/He,. cap alpha. )/sup 57/Ni reaction. [15 to 205 GeV, finite-range and nonlocality corrections

Energy Technology Data Exchange (ETDEWEB)

Shepard, J R; Zimmerman, W R; Kraushaar, J J [Colorado Univ., Boulder (USA). Dept. of Physics and Astrophysics

1977-01-04

Strong transitions in the /sup 58/Ni(/sup 3/He,..cap alpha..)/sup 57/Ni reaction were analyzed using both the zero-range and exact finite-range DWBA. Data considered covered a range of bombarding energies from 15 to 205 MeV. The zero-range DWBA described all data well when finite-range and non-locality corrections were included in the local energy approximation. Comparison of zero-range and exact finite-range calculations showed the local energy approximation correction to be very accurate over the entire energy region. Empirically determined D/sub 0/ values showed no energy dependence. A theoretical D/sub 0/ value calculated using an ..cap alpha.. wave function which reproduced the measured ..cap alpha.. rms charge radius and the elastic electron scattering form factor agreed well the empirical values. Comparison was made between these values and D/sub 0/ values quoted previously in the literature.

The Effect of Multidentate Biopolymer Based on Polyacrylamide Grafted onto Kappa-Carrageenan on the Spectrofluorometric Properties of Water-Soluble CdS Quantum Dots

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Ghasem Rezanejade Bardajee

2011-01-01

Full Text Available A new fluorescent composite based on CdS quantum dots immobilized on the multidentate biopolymer matrix is prepared through the graft copolymerization of the acrylamide onto kappa-Carrageenan. A variety of techniques like thermogravimetric analysis (TGA, transmission electron microscopy (TEM, and Fourier transform infrared spectroscopy (FT-IR was used to confirm the structure of the obtained samples. To investigate the spectrofluorometric properties, fluorescence spectroscopy of the obtained quantum dots was studied.

Value for money: Defining and measuring 'value' in MoD's acquisition policy of obtaining best value for money

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