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Sample records for fp prostanoid receptors

  1. Infusion of oxytocin induces successful delivery in prostanoid FP-receptor-deficient mice.

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    Kawamata, Masaki; Yoshida, Masahide; Sugimoto, Yukihiko; Kimura, Tadashi; Tonomura, Yutaka; Takayanagi, Yuki; Yanagisawa, Teruyuki; Nishimori, Katsuhiko

    2008-02-13

    The dramatic increase of oxytocin (OT) receptor (OTR) in the myometrium as well as circulating progesterone withdrawal has been thought to be the most important factor in the induction and accomplishment of parturition since delivery fails in prostaglandin F2alpha receptor (FP) knockout (FP KO) mice. The expression levels of OTR mRNA/protein were not dramatically increased in the near-term uteri of FP KO mice. However, OT-induced myometrial contractions and the concentration-response curves in FP KO in vitro were almost similar to those in wild-type (WT) mice. OT-infusion (0.3 U/day) enabled FP KO mice to experience successful delivery, and furthermore the duration until the onset was hastened by a higher dose of OT (3 U/day). The plasma progesterone levels of FP KO females were maintained at high levels, but decreased during labor by OT-infusion (3 U/day). These results suggest that OT has potentials to induce strong myometrial contractions in uterus with low expression levels of OTR and luteolysis in ovary, which enabled FP KO females to undergo successful delivery.

  2. Prostanoid Receptors in the Human Vascular Wall

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    Xavier Norel

    2007-01-01

    Full Text Available The mechanisms involved in vascular homeostasis and disease are mostly dependent on the interactions between blood, vascular smooth muscle, and endothelial cells. There is an accumulation of evidence for the involvement of prostanoids, the arachidonic acid metabolites derived from the cyclooxygenase enzymatic pathway, in physiological and/or pathophysiological conditions. In humans, the prostanoids activate different receptors. The classical prostanoid receptors (DP, EP1–4, FP, IP, and TP are localized at the cell plasma or nuclear membrane. In addition, CRTH2 and the nuclear PPAR receptors are two other targets for prostanoids, namely, prostacyclin (PGI2 or the natural derivatives of prostaglandin D2. While there is little information on the role of CRTH2, there are many reports on PPAR activation and the consecutive expression of genes involved in the human vascular system. The role of the classical prostanoid receptors stimulated by PGI2 and thromboxane in the control of the vascular tone has been largely documented, whereas the other receptor subtypes have been overlooked. There is now increasing evidence that suggests a role of PGE2 and the EP receptor subtypes in the control of the human vascular tone and remodeling of the vascular wall. These receptors are also present on leukocytes and platelets, and they are implicated in most of the inflammatory processes within the vascular wall. Consequently, the EP receptor subtypes or isoforms would provide a novel and specific cardiovascular therapeutic approach in the near future.

  3. Prostanoid receptors involved in regulation of the beating rate of neonatal rat cardiomyocytes.

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    Hakima Mechiche

    Full Text Available Although prostanoids are known to be involved in regulation of the spontaneous beating rate of cultured neonatal rat cardiomyocytes, the various subtypes of prostanoid receptors have not been investigated in detail. In our experiments, prostaglandin (PGF(2α and prostanoid FP receptor agonists (fluprostenol, latanoprost and cloprostenol produced a decrease in the beating rate. Two prostanoid IP receptor agonists (iloprost and beraprost induced first a marked drop in the beating rate and then definitive abrogation of beating. In contrast, the prostanoid DP receptor agonists (PGD(2 and BW245C and TP receptor agonists (U-46619 produced increases in the beating rate. Sulprostone (a prostanoid EP(1 and EP(3 receptor agonist induced marked increases in the beating rate, which were suppressed by SC-19220 (a selective prostanoid EP(1 antagonist. Butaprost (a selective prostanoid EP(2 receptor agonist, misoprostol (a prostanoid EP(2 and EP(3 receptor agonist, 11-deoxy-PGE(1 (a prostanoid EP(2, EP(3 and EP(4 receptor agonist did not alter the beating rate. Our results strongly suggest that prostanoid EP(1 receptors are involved in positive regulation of the beating rate. Prostanoid EP(1 receptor expression was confirmed by western blotting with a selective antibody. Hence, neonatal rat cardiomyocytes express both prostanoid IP and FP receptors (which negatively regulate the spontaneous beating rate and prostanoid TP, DP(1 and EP(1 receptors (which positively regulate the spontaneous beating rate.

  4. 8-iso-PGE2 stimulates anion efflux from airway epithelial cells via the EP4 prostanoid receptor.

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    Joy, Andrew P; Cowley, Elizabeth A

    2008-02-01

    Isoprostanes are biologically active molecules, produced when reactive oxygen species mediate the peroxidation of membrane polyunsaturated fatty acids. Previous work has demonstrated that the isoprostane 8-iso-prostaglandin E(2) (PGE(2)) stimulates cystic fibrosis transmembrane conductance regulator (CFTR)-mediated transepithelial anion secretion across the human airway epithelial cell line, Calu-3. Since isoprostanes predominantly achieve their effects via binding to prostanoid receptors, we hypothesized that this 8-iso-PGE(2) stimulation of CFTR activity was the result of the isoprostane binding to a prostanoid receptor. Using RT-PCR, immunoblotting, and immunofluorescence, we here demonstrate that Calu-3 cells express the EP(1-4) and FP receptors, and localize these proteins in polarized cell monolayers. Using iodide efflux as a marker for CFTR-mediated Cl(-) efflux, we investigate whether prostanoid receptor agonists elicit a functional response from Calu-3 cells. Application of the agonists PGE(2), misoprostol (EP(2), EP(3), and EP(4)) and PGE(1)-OH (EP(3) and EP(4)) stimulate iodide efflux; however, iloprost, butaprost, sulprostone, and fluoprostenol (agonists of the EP(1), EP(2), EP(3), and FP receptors, respectively) have no effect. The iodide efflux seen with 8-iso-PGE(2) is abolished by the EP(4) receptor antagonist AH23848, the CFTR inhibitor 172, and inhibition of PKA and the PI3K pathway. In conclusion, we demonstrate that although Calu-3 cells possess numerous prostanoid receptors, only the EP(4) subtype appears capable of eliciting a functional iodide efflux response, which is mediated via the EP(4) receptor. We propose that 8-iso-PGE(2), acting via EP(4) receptor, could play an important role in the CFTR-mediated response to oxidant stress, and which would be compromised in the CF airways.

  5. Prostanoid receptor EP2 as a therapeutic target.

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    Ganesh, Thota

    2014-06-12

    Cycoloxygenase-2 (COX-2) induction is prevalent in a variety of (brain and peripheral) injury models where COX-2 levels correlate with disease progression. Thus, COX-2 has been widely explored for anti-inflammatory therapy with COX-2 inhibitors, which proved to be effective in reducing the pain and inflammation in patients with arthritis and menstrual cramps, but they have not provided any benefit to patients with chronic inflammatory neurodegenerative disease. Recently, two COX-2 drugs, rofecoxib and valdecoxib, were withdrawn from the United States market due to cardiovascular side effects. Thus, future anti-inflammatory therapy could be targeted through a specific prostanoid receptor downstream of COX-2. The PGE2 receptor EP2 is emerging as a pro-inflammatory target in a variety of CNS and peripheral diseases. Here we highlight the latest developments on the role of EP2 in diseases, mechanism of activation, and small molecule discovery targeted either to enhance or to block the function of this receptor.

  6. Piglet saphenous vein contains multiple relaxatory prostanoid receptors: evidence for EP4, EP2, DP and IP receptor subtypes

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    Wilson, Richard J; Giles, Heather

    2005-01-01

    Prostaglandin E2 produced endothelium-independent relaxation of phenylephrine- and 5-HT-contracted piglet saphenous vein (PSV; pEC50=8.6±0.2; n=6).The prostanoid EP4 receptor antagonist GW627368X (30–300 nM) produced parallel rightward displacement of PGE2 concentration–effect (E/[A]) curves (pKb=9.2±0.2; slope=1). Higher concentrations of GW627368X did not produce further rightward shifts, revealing the presence of non-EP4 prostanoid receptors.In all, 18 other prostanoid receptor agonists re...

  7. Prostaglandin E2 inhibits mast cell-dependent bronchoconstriction in human small airways through the E prostanoid subtype 2 receptor.

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    Säfholm, Jesper; Manson, Martijn L; Bood, Johan; Delin, Ingrid; Orre, Ann-Charlotte; Bergman, Per; Al-Ameri, Mamdoh; Dahlén, Sven-Erik; Adner, Mikael

    2015-11-01

    Inhaled prostaglandin (PG) E2 might inhibit asthmatic responses, but the mechanisms involved remain undefined. We sought to characterize the direct and indirect effects of PGE2 on human small airways with particular reference to the receptors mediating the responses. Contraction and relaxation were studied in isolated human bronchi with an inner diameter of 1 mm or less. Low concentrations of PGE2 (0.01-1 μmol/L) relaxed the bronchi precontracted by histamine. The bronchodilator response was inhibited by the E prostanoid (EP) subtype 4 receptor antagonist ONO-AE3-208 but unaffected by the EP2 receptor antagonist PF-04418948. Higher concentrations of PGE2 (10-100 μmol/L) contracted the small airways. However, the TP receptor agonists U-46,619, PGF2α, and PGD2 were more potent than PGE2. Moreover, the bronchoconstrictor responses to PGE2 and all other tested prostanoids, including the EP1/EP3 receptor agonist 17-phenyl trinor PGE2 and the partial FP receptor agonist AL-8810, were uniformly abolished by the TP receptor antagonist SQ-29,548. In the presence of TP and EP4 antagonists, PGE2 inhibited the mast cell-mediated bronchoconstriction resulting from anti-IgE challenge. Measurement of the release of histamine and cysteinyl leukotrienes documented that this bronchoprotective action of PGE2 was mediated by the EP2 receptor, unrelated to bronchodilation, and increased with time of exposure. The pharmacology of PGE2 in isolated human small airways was different from its profile in animal models. This first demonstration of powerful EP2 receptor-mediated inhibition of IgE-dependent contractions in human airways introduces a new selective target for the treatment of asthma. This EP2 control of mast cell-mediated bronchoconstriction is presumably exaggerated in patients with aspirin-exacerbated respiratory disease. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  8. Binding and activity of the prostacyclin receptor (IP) agonists, treprostinil and iloprost, at human prostanoid receptors: treprostinil is a potent DP1 and EP2 agonist.

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    Whittle, Brendan J; Silverstein, Adam M; Mottola, David M; Clapp, Lucie H

    2012-07-01

    The prostacyclin analogues, iloprost and treprostinil are extensively used in treating pulmonary hypertension. Their binding profile and corresponding biochemical cellular responses on human prostanoid receptors expressed in cell lines, have now been compared. Iloprost had high binding affinity for EP1 and IP receptors (Ki 1.1 and 3.9 nM, respectively), low affinity for FP, EP3 or EP4 receptors, and very low affinity for EP2, DP1 or TP receptors. By contrast, treprostinil had high affinity for the DP1, EP2 and IP receptors (Ki 4.4, 3.6 and 32 nM, respectively), low affinity for EP1 and EP4 receptors and even lower affinity for EP3, FP and TP receptors. In functional assays, iloprost had similar high activity in elevating cyclic AMP levels in cells expressing the human IP receptor and stimulating calcium influx in cells expressing EP1 receptors (EC50 0.37 and 0.3 nM, respectively) with the rank order of activity on the other receptors comparable to the binding assays. As with binding studies, treprostinil elevated cyclic AMP with a similar high potency in cells expressing DP1, IP and EP2 receptors (EC50 0.6, 1.9 and 6.2 nM, respectively), but had low activity at the other receptors. Activation of IP, DP1 and EP2 receptors, as with treprostinil, can all result in vasodilatation of human pulmonary arteries. However, activation of EP1 receptors can provoke vasoconstriction, and hence may offset the IP-receptor mediated vasodilator effects of iloprost. Treprostinil may therefore differ from iloprost in its overall beneficial pulmonary vasorelaxant profile and other pharmacological actions, especially in diseases where the IP receptor is down-regulated. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Phosphorylation of glycogen synthase kinase-3 and stimulation of T-cell factor signaling following activation of EP2 and EP4 prostanoid receptors by prostaglandin E2.

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    Fujino, Hiromichi; West, Kimberly A; Regan, John W

    2002-01-25

    Recently we have shown that the FP(B) prostanoid receptor, a G-protein-coupled receptor that couples to Galpha(q), activates T-cell factor (Tcf)/lymphoid enhancer factor (Lef)-mediated transcriptional activation (Fujino, H., and Regan, J. W. (2001) J. Biol. Chem. 276, 12489-12492). We now report that the EP(2) and EP(4) prostanoid receptors, which couple to Galpha(s), also activate Tcf/Lef signaling. By using a Tcf/Lef-responsive luciferase reporter gene, transcriptional activity was stimulated approximately 10-fold over basal by 1 h of treatment with prostaglandin E(2) (PGE(2)) in HEK cells that were stably transfected with the human EP(2) and EP(4) receptors. This stimulation of reporter gene activity was accompanied by a PGE(2)-dependent increase in the phosphorylation of both glycogen synthase kinase-3 (GSK-3) and Akt kinase. H-89, an inhibitor of protein kinase A (PKA), completely blocked the agonist-dependent phosphorylation of GSK-3 in both EP(2)- and EP(4)-expressing cells. However, H-89 pretreatment only blocked PGE(2)-stimulated Lef/Tcf reporter gene activity by 20% in EP(4)-expressing cells compared with 65% inhibition in EP(2)-expressing cells. On the other hand wortmannin, an inhibitor of phosphatidylinositol 3-kinase, had the opposite effect and inhibited PGE(2)-stimulated reporter gene activity to a much greater extent in EP(4)-expressing cells as compared with EP(2)-expressing cells. These findings indicate that the activation of Tcf/Lef signaling by EP(2) receptors occurs primarily through a PKA-dependent pathway, whereas EP(4) receptors activate Tcf/Lef signaling mainly through a phosphatidylinositol 3-kinase-dependent pathway. This is the first indication of a fundamental difference in the signaling potential of EP(2) and EP(4) prostanoid receptors.

  10. In vivo studies validating multitargeting of prostanoid receptors for achieving superior anti-inflammatory effects.

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    Woodward, David F; Wang, Jenny W; Ni, Ming; Bauer, Alex; Martos, Jose L; Carling, Robert W; Poloso, Neil J

    2017-01-01

    The purpose of these studies was to test the hypothesis that a selected polypharmacological approach for treating the prostanoid-mediated component of inflammatory diseases would produce a therapeutic effect superior to global inhibition of prostaglandin (PG) biosynthesis by aspirin-like drugs. The compound studied was AGN 211377, which had been previously shown to produce a superior effect on cytokine release from human macrophages compared with cyclooxygenase (COX) inhibitors. AGN 211377 antagonizes prostanoid prostaglandin D2 (DP)1, DP2, prostaglandin E2 (EP)1, EP4, prostaglandin F2α, and thromboxane A2 receptors but not anti-inflammatory EP2, prostaglandin I2, or EP3 receptors. Established rodent models of ocular inflammatory diseases were used to determine therapeutic effects in living animals. The drugs were administered systemically after predetermination of their blood levels to ensure bioavailability at an appropriate dose level. Whereas compounds selective for a single prostanoid receptor typically exhibited modest but statistically significant inhibition, AGN 211377 profoundly inhibited S-antigen-induced uveitis and laser-induced retinal neovascularization. Consistent with previous polypharmacological studies on chemokine/cytokine release from human macrophages, the prostanoid EP1 receptor played a permissive role in suppressing neovascularization and inflammation in vivo Comparing AGN 211377 with a close structural congener lacking EP1 antagonism (AGN 197727), AGN 197727 was much less active than AGN 211377, but pronounced anti-inflammatory and angiostatic effects were achieved by adding the EP1 antagonist compound (SC-51322) to AGN 197727 in the systemic dosing regimen. Further, AGN 211377 produced superior anti-inflammatory activity compared with the nonsteroidal anti-inflammatory agent ketorolac. These results indicate the value of using a polypharmacological approach in the design of novel therapeutic agents in preference to compounds targeting a

  11. Prostaglandin E₂ inhibits human lung fibroblast chemotaxis through disparate actions on different E-prostanoid receptors.

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    Li, Ying-Ji; Wang, Xing-Qi; Sato, Tadashi; Kanaji, Nobuhiro; Nakanishi, Masanori; Kim, Miok; Michalski, Joel; Nelson, Amy J; Sun, Jian-Hong; Farid, Maha; Basma, Hesham; Patil, Amol; Toews, Myron L; Liu, Xiangde; Rennard, Stephen I

    2011-01-01

    The migration of fibroblasts is believed to play a key role in both normal wound repair and abnormal tissue remodeling. Prostaglandin E (PGE)(2), a mediator that can inhibit many fibroblast functions including chemotaxis, was reported to be mediated by the E-prostanoid (EP) receptor EP2. PGE(2), however, can act on four receptors. This study was designed to determine if EP receptors, in addition to EP2, can modulate fibroblast chemotaxis. Using human fetal lung fibroblasts, the expression of all four EP receptors was demonstrated by Western blotting. EP2-selective and EP4-selective agonists inhibited both chemotaxis toward fibronectin in the blindwell assay and migration in a wound-closure assay. In contrast, EP1-selective and EP3-selective agonists stimulated cell migration in both assay systems. These results were confirmed using EP-selective antagonists. The role of both EP2 and EP4 receptors in mediating the PGE(2) inhibition of chemotaxis was also confirmed by small interfering RNA suppression. Furthermore, the role of EP receptors was confirmed by blocking the expected signaling pathways. Taken together, these results demonstrate that PGE(2) can act on multiple EP receptors in human lung fibroblasts, to exert disparate effects. Alterations in EP receptor expression may have the potential to alter PGE(2) action. Targeting specific EP receptors may offer therapeutic opportunities in conditions characterized by abnormal tissue repair and remodeling.

  12. E-type prostanoid receptor 4 (EP4) in disease and therapy

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    Konya, Viktoria; Marsche, Gunther; Schuligoi, Rufina; Heinemann, Akos

    2013-01-01

    The large variety of biological functions governed by prostaglandin (PG) E2 is mediated by signaling through four distinct E-type prostanoid (EP) receptors. The availability of mouse strains with genetic ablation of each EP receptor subtype and the development of selective EP agonists and antagonists have tremendously advanced our understanding of PGE2 as a physiologically and clinically relevant mediator. Moreover, studies using disease models revealed numerous conditions in which distinct EP receptors might be exploited therapeutically. In this context, the EP4 receptor is currently emerging as most versatile and promising among PGE2 receptors. Anti-inflammatory, anti-thrombotic and vasoprotective effects have been proposed for the EP4 receptor, along with its recently described unfavorable tumor-promoting and pro-angiogenic roles. A possible explanation for the diverse biological functions of EP4 might be the multiple signaling pathways switched on upon EP4 activation. The present review attempts to summarize the EP4 receptor-triggered signaling modules and the possible therapeutic applications of EP4-selective agonists and antagonists. PMID:23523686

  13. Fluid flow shear stress upregulates prostanoid receptor EP2 but not EP4 in murine podocytes.

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    Srivastava, Tarak; McCarthy, Ellen T; Sharma, Ram; Kats, Alexander; Carlton, Carol G; Alon, Uri S; Cudmore, Patricia A; El-Meanawy, Ashraf; Sharma, Mukut

    2013-01-01

    Podocytes in the glomerular filtration barrier regulate the passage of plasma proteins into urine. Capillary pressure and ultrafiltration impact the structure and function of podocytes. The mechanism of podocyte injury by fluid flow shear stress (FFSS) from hyperfiltration in chronic kidney disease (CKD) is not completely understood. Recently, we demonstrated increased synthesis of prostaglandin E2 in podocytes exposed to FFSS. Here, we determine the effect of FFSS on prostanoid receptors EP1-EP4 in cultured podocytes and in Os/+ mouse kidney, a model of hyperfiltration. Results of RT-PCR, qRT-PCR, immunoblotting and immunofluorescence studies indicate that cultured podocytes express EP1, EP2 and EP4 but not EP3. FFSS resulted in upregulated expression of only EP2 in podocytes. Kidney immunostaining showed significantly increased expression of EP2 in Os/+ mice compared with littermate controls. These novel results suggest that EP2 may be responsible for mediating podocyte injury from hyperfiltration-induced augmented FFSS in CKD.

  14. Inverse agonist and pharmacochaperone properties of MK-0524 on the prostanoid DP1 receptor.

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    Pascale Labrecque

    Full Text Available Prostaglandin D₂ (PGD₂ acts through two G protein-coupled receptors (GPCRs, the prostanoid DP receptor and CRTH2 also known as DP1 and DP2, respectively. Several previously characterized GPCR antagonists are now classified as inverse agonists and a number of GPCR ligands are known to display pharmacochaperone activity towards a given receptor. Here, we demonstrate that a DP1 specific antagonist, MK-0524 (also known as laropiprant, decreased basal levels of intracellular cAMP produced by DP1, a Gα(s-coupled receptor, in HEK293 cells. This reduction in cAMP levels was not altered by pertussis toxin treatment, indicating that MK-0524 did not induce coupling of DP1 to Gα(i/o proteins and that this ligand is a DP1 inverse agonist. Basal ERK1/2 activation by DP1 was not modulated by MK-0524. Interestingly, treatment of HEK293 cells expressing Flag-tagged DP1 with MK-0524 promoted DP1 cell surface expression time-dependently to reach a maximum increase of 50% compared to control after 24 h. In contrast, PGD₂ induced the internalization of 75% of cell surface DP1 after the same time of stimulation. The increase in DP1 cell surface targeting by MK-0524 was inhibited by Brefeldin A, an inhibitor of transport from the endoplasmic reticulum-Golgi to the plasma membrane. Confocal microscopy confirmed that a large population of DP1 remained trapped intracellularly and co-localized with calnexin, an endoplasmic reticulum marker. Redistribution of DP1 from intracellular compartments to the plasma membrane was observed following treatment with MK-0524 for 24 h. Furthermore, MK-0524 promoted the interaction between DP1 and the ANKRD13C protein, which we showed previously to display chaperone-like effects towards the receptor. We thus report that MK-0524 is an inverse agonist and a pharmacochaperone of DP1. Our findings may have important implications during therapeutic treatments with MK-0524 and for the development of new molecules targeting DP1.

  15. Why does the agonist [{sup 18}F]FP-TZTP bind preferentially to the M{sub 2} muscarinic receptor?

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    Ravasi, L. [National Institutes of Health, PET Radiochemistry Group, National Institute for Biomedical Imaging and Bioengineering, Bethesda, MD (United States); Universita degli Studi di Milano, Institute of Radiological Sciences, Milan (Italy); Kiesewetter, D.O.; Shimoji, K. [National Institutes of Health, PET Radiochemistry Group, National Institute for Biomedical Imaging and Bioengineering, Bethesda, MD (United States); Lucignani, G. [Universita degli Studi di Milano, Institute of Radiological Sciences, Milan (Italy); European Institute of Oncology, Unit of Molecular Imaging, Division of Radiation Therapy, Milan (Italy); Eckelman, W.C. [National Institutes of Health, PET Department, Clinical Center, Bethesda, MD (United States); Molecular Tracer LLC, Bethesda, MD (United States)

    2006-03-15

    Preferential binding of FP-TZTP at the M{sub 2} receptor in vivo led to investigation of [{sup 18}F]FP-TZTP as a potential PET tracer for Alzheimer's disease, in which a substantial reduction of M{sub 2} receptors has been observed in autopsy studies. We hereby investigated in vitro the FP-TZTP behavior to further elucidate the properties of FP-TZTP that lead to its M{sub 2} selectivity. Chinese hamster ovarian cells expressing the five subtypes of human muscarinic receptor as well as the wild type were harvested in culture to assess equilibrium binding. Specific binding was calculated by subtraction of non-specific binding from total binding. Internal specific binding was calculated by subtraction of external specific binding from the total specific binding. Saturation assays were also performed to calculate B{sub max}, K{sub i}, and IC{sub 50}. In addition, equilibrium binding and dissociation kinetic studies were performed on rat brain tissue. Selected regions of interest were drawn on the digital autoradiograms and [{sup 18}F]FP-TZTP off-rates were determined by measurement of the rate of release into a buffer solution of [{sup 18}F]FP-TZTP from slide-bound cells that had been preincubated with [{sup 18}F]FP-TZTP. At equilibrium in vitro, M{sub 2} subtype selectivity of [{sup 18}F]FP-TZTP was not evident. We demonstrated that ATP-dependent mechanisms are not responsible for FP-TZTP M{sub 2} selectivity. In vitro off-rate studies from rat brain tissue showed that the off-rate of FP-TZTP varied with the percentage of M{sub 2} subtype in the tissue region. The slower dissociation kinetics of FP-TZTP from M{sub 2} receptors compared with the four other muscarinic receptor subtypes may be a factor in its M{sub 2} selectivity. (orig.)

  16. Differential peristaltic motor effects of prostanoid (DP, EP, IP, TP) and leukotriene receptor agonists in the guinea-pig isolated small intestine

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    Shahbazian, Anaid; Heinemann, Akos; Peskar, Bernhard A; Holzer, Peter

    2002-01-01

    Since the role of prostanoid receptors in intestinal peristalsis is largely unknown, the peristaltic motor effects of some prostaglandin (DP, EP, IP), thromboxane (TP) and leukotriene (LT) receptor agonists and antagonists were investigated.Propulsive peristalsis in fluid-perfused segments from the guinea-pig small intestine was triggered by a rise of the intraluminal pressure and recorded via the intraluminal pressure changes associated with the peristaltic waves. Alterations of distension s...

  17. In vivo intra-luteal implants of prostaglandin (PG) E1 or E2 (PGE1, PGE2) prevent luteolysis in cows. II: mRNA for PGF2α, EP1, EP2, EP3 (A-D), EP3A, EP3B, EP3C, EP3D, and EP4 prostanoid receptors in luteal tissue.

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    Weems, Yoshie S; Bridges, Phillip J; Jeoung, Myoungkun; Arreguin-Arevalo, J Alejandro; Nett, Torrance M; Vann, Rhonda C; Ford, Stephen P; Lewis, Andrew W; Neuendorff, Don A; Welsh, Thomas H; Randel, Ronald D; Weems, Charles W

    2012-01-01

    Previously, it was reported that chronic intra-uterine infusion of PGE(1) or PGE(2) every 4h inhibited luteolysis in ewes by altering luteal mRNA for luteinizing hormone (LH) receptors and unoccupied and occupied luteal LH receptors. However, estradiol-17β or PGE(2) given intra-uterine every 8h did not inhibit luteolysis in cows, but infusion of estradiol+PGE(2) inhibited luteolysis. In contrast, intra-luteal implants containing PGE(1) or PGE(2) in Angus or Brahman cows also inhibited the decline in circulating progesterone, mRNA for LH receptors, and loss of unoccupied and occupied receptors for LH to prevent luteolysis. The objective of this experiment was to determine how intra-luteal implants of PGE(1) or PGE(2) alter mRNA for prostanoid receptors and how this could influence luteolysis in Brahman or Angus cows. On day-13 Angus cows received no intra-luteal implant and corpora lutea were retrieved or Angus and Brahman cows received intra-luteal silastic implants containing Vehicle, PGE(1), or PGE(2) and corpora lutea were retrieved on day-19. Corpora lutea slices were analyzed for mRNA for prostanoid receptors (FP, EP1, EP2, EP3 (A-D), EP3A, EP3B, EP3C, EP3D, and EP4) by RT-PCR. Day-13 Angus cow luteal tissue served as pre-luteolytic controls. mRNA for FP receptors decreased in day-19 Vehicle controls compared to day-13 Vehicle controls regardless of breed. PGE(1) and PGE(2) up-regulated FP gene expression on day-19 compared to day-19 Vehicle controls regardless of breed. EP1 mRNA was not altered by any treatment. PGE(1) and PGE(2) down-regulated EP2 and EP4 mRNA compared to day-19 Vehicle controls regardless of breed. PGE(1) or PGE(2) up-regulated mRNA EP3B receptor subtype compared to day-19 Vehicle control cows regardless of breed. The similarities in relative gene expression profiles induced by PGE(1) and PGE(2) support their agonistic effects. We conclude that both PGE(1) and PGE(2) may prevent luteolysis by altering expression of mRNA for prostanoid

  18. Prostaglandin E2 suppresses beta1-integrin expression via E-prostanoid receptor in human monocytes/macrophages.

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    Hasegawa, Shunji; Ichiyama, Takashi; Kohno, Fumitaka; Korenaga, Yuno; Ohsaki, Ayami; Hirano, Reiji; Haneda, Yasuhiro; Fukano, Reiji; Furukawa, Susumu

    2010-01-01

    Beta1-integrins mediate cell attachment to different extracellular matrix proteins, intracellular proteins, and intercellular adhesions. Recently, it has been reported that prostaglandin E2 (PGE2) has anti-inflammatory properties such as inhibition of the expression of adhesion molecules or production of chemokines. However, the effect of PGE2 on the expression of beta1-integrin remains unknown. In this study, we investigated the effects of PGE2 on the expression of beta1-integrin in the human monocytic cell line THP-1 and in CD14+ monocytes/macrophages in human peripheral blood. For this, we examined the role of four subtypes of PGE2 receptors and E-prostanoid (EP) receptors on PGE2-mediated inhibition. We found that PGE2 significantly inhibited the expression of beta1-integrin, mainly through EP4 receptors in THP-1 cells and CD14+ monocytes/macrophages in human peripheral blood. We suggest that PGE2 has anti-inflammatory effects, leading to the inhibited expression of beta1-integrin in human monocytes/macrophages, and that the EP4 receptor may play an important role in PGE2-mediated inhibition. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  19. Activation of the signaling cascade in response to T lymphocyte receptor stimulation and prostanoids in a case of cutaneous lupus

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    Ana Maria Abreu-Velez

    2011-01-01

    Full Text Available Context: Discoid lupus erythematosus is a chronic inflammatory skin disorder presenting with scarring lesions that occur predominately on sun exposed areas of the face and scalp. Case Report: A 22-year-old male was evaluated after presenting with reddish-purple, atrophic and erythematous plaques on the scalp, with loss of hair within the plaques. Biopsies for hematoxylin and eosin examination, direct immunofluorescence and immunohistochemistry analysis were performed. The hematoxylin and eosin staining demonstrated classic features of cutaneous lupus. Direct immunofluorescence revealed strong deposits of immunoglobulins IgG and IgM, fibrinogen and Complement/C3, present in 1 a shaggy pattern at the epidermal basement membrane zone, and 2 focal pericytoplasmic and perinuclear staining within epidermal keratynocytes. Immunohistochemisty staining revealed strongly positive staining with antibodies to cyclooxygenase-2, Zeta-chain-associated protein kinase 70, and HLA-DPDQDR in areas where the inflammatory infiltrate was predominant, as well as around dermal blood vessels and within the dermal extracellular matrix. Conclusions : Noting the autoimmune nature of lupus and its strong inflammatory component, we present a patient with active discoid lupus erythematosus and strong expression of Zeta-chain-associated protein kinase 70, cyclo-oxygenase-2, and HLA-DPDQDR in the inflammatory areas. We suggest that these molecules may play a significant role in the immune response of discoid cutaneous lupus, possibly including 1 the biosynthesis of the prostanoids and 2 activation of the signaling cascade in response to T-lymphocyte receptor stimulation.

  20. Prostaglandin E2 prevents hyperosmolar-induced human mast cell activation through prostanoid receptors EP2 and EP4.

    Directory of Open Access Journals (Sweden)

    Ivonne Torres-Atencio

    Full Text Available BACKGROUND: Mast cells play a critical role in allergic and inflammatory diseases, including exercise-induced bronchoconstriction (EIB in asthma. The mechanism underlying EIB is probably related to increased airway fluid osmolarity that activates mast cells to the release inflammatory mediators. These mediators then act on bronchial smooth muscle to cause bronchoconstriction. In parallel, protective substances such as prostaglandin E2 (PGE2 are probably also released and could explain the refractory period observed in patients with EIB. OBJECTIVE: This study aimed to evaluate the protective effect of PGE2 on osmotically activated mast cells, as a model of exercise-induced bronchoconstriction. METHODS: We used LAD2, HMC-1, CD34-positive, and human lung mast cell lines. Cells underwent a mannitol challenge, and the effects of PGE2 and prostanoid receptor (EP antagonists for EP(1-4 were assayed on the activated mast cells. Beta-hexosaminidase release, protein phosphorylation, and calcium mobilization were assessed. RESULTS: Mannitol both induced mast cell degranulation and activated phosphatidyl inositide 3-kinase and mitogen-activated protein kinase (MAPK pathways, thereby causing de novo eicosanoid and cytokine synthesis. The addition of PGE2 significantly reduced mannitol-induced degranulation through EP(2 and EP(4 receptors, as measured by beta-hexosaminidase release, and consequently calcium influx. Extracellular-signal-regulated kinase 1/2, c-Jun N-terminal kinase, and p38 phosphorylation were diminished when compared with mannitol activation alone. CONCLUSIONS: Our data show a protective role for the PGE2 receptors EP(2 and EP(4 following osmotic changes, through the reduction of human mast cell activity caused by calcium influx impairment and MAP kinase inhibition.

  1. Prostanoids in tumor angiogenesis: therapeutic intervention beyond COX-2.

    Science.gov (United States)

    Salvado, M Dolores; Alfranca, Arántzazu; Haeggström, Jesper Z; Redondo, Juan Miguel

    2012-04-01

    Prostanoids regulate angiogenesis in carcinoma and chronic inflammatory disease progression. Although prostanoid biosynthetic enzymes and signaling have been extensively analyzed in inflammation, little is known about how prostanoids mediate tumor-induced angiogenesis. Targeted cyclooxygenase (COX)-2 inhibition in tumor, stromal and endothelial cells is an attractive antiangiogenic strategy; however, the associated cardiovascular side effects have led to the development of a new generation of nonsteroidal anti-inflammatory drugs (NSAIDs) acting downstream of COX. These agents target terminal prostanoid synthases and prostanoid receptors, which may also include several peroxisome proliferator-activated receptors (PPARs). Here, we discuss the role of prostanoids as modulators of tumor angiogenesis and how prostanoid metabolism reflects complex cell-cell crosstalk that determines tumor growth. Finally, we discuss the potential of new NSAIDs for the treatment of angiogenesis-dependent tumor development.

  2. Stimulation of fat storage by prostacyclin and selective agonists of prostanoid IP receptor during the maturation phase of cultured adipocytes.

    Science.gov (United States)

    Khan, Ferdous; Syeda, Pinky Karim; Nartey, Michael Nii N; Rahman, Mohammad Shahidur; Islam, Mohammad Safiqul; Nishimura, Kohji; Jisaka, Mitsuo; Shono, Fumiaki; Yokota, Kazushige

    2016-12-01

    We have previously shown that cultured adipocytes have the ability to biosynthesize prostaglandin (PG) I2 called alternatively as prostacyclin during the maturation phase by the positive regulation of gene expression of PGI synthase and the prostanoid IP receptor. To clarify how prostacyclin regulates adipogenesis, we investigated the effects of prostacyclin and the specific agonists or antagonists for the IP receptor on the storage of fats during the maturation phase of cultured adipocytes. Exogenous PGI2 and the related selective agonists for the IP receptor including MRE-269 and treprostinil rescued the storage of fats attenuated by aspirin, a cyclooxygenase inhibitor. On the other hand, selective antagonists for IP such as CAY10441 and CAY10449 were effective to suppress the accumulation of fats as GW9662, a specific antagonist for peroxisome proliferator-activated receptor (PPAR)γ. Thus, pro-adipogenic action of prostacyclin can be explained by the action mediated through the IP receptor expressed at the maturation stage of adipocytes. Cultured adipocytes incubated with each of PGI2 and MRE-269 together with troglitazone, an activator for PPARγ, exhibited additively higher stimulation of fats storage than with either compound alone. The combined effect of MRE-269 and troglitazone was almost abolished by co-incubation with GW9662, but not with CAY10441. Increasing concentrations of troglitazone were found to reverse the inhibitory effect of CAY10441 in a dose-dependent manner while those of MRE-269 failed to rescue adipogenesis suppressed by GW9662, indicating the critical role of the PPARγ activation as a downstream factor for the stimulated adipogenesis through the IP receptor. Treatment of cultured adipocytes with cell permeable stable cAMP analogues or forskolin as a cAMP elevating agent partly restored the inhibitory effect of aspirin. However, excess levels of cAMP stimulated by forskolin attenuated adipogenesis. Supplementation with H-89, a cell

  3. Activation of E-prostanoid 3 receptor in macrophages facilitates cardiac healing after myocardial infarction

    Science.gov (United States)

    Tang, Juan; Shen, Yujun; Chen, Guilin; Wan, Qiangyou; Wang, Kai; Zhang, Jian; Qin, Jing; Liu, Guizhu; Zuo, Shengkai; Tao, Bo; Yu, Yu; Wang, Junwen; Lazarus, Michael; Yu, Ying

    2017-01-01

    Two distinct monocyte (Mo)/macrophage (Mp) subsets (Ly6Clow and Ly6Chigh) orchestrate cardiac recovery process following myocardial infarction (MI). Prostaglandin (PG) E2 is involved in the Mo/Mp-mediated inflammatory response, however, the role of its receptors in Mos/Mps in cardiac healing remains to be determined. Here we show that pharmacological inhibition or gene ablation of the Ep3 receptor in mice suppresses accumulation of Ly6Clow Mos/Mps in infarcted hearts. Ep3 deletion in Mos/Mps markedly attenuates healing after MI by reducing neovascularization in peri-infarct zones. Ep3 deficiency diminishes CX3C chemokine receptor 1 (CX3CR1) expression and vascular endothelial growth factor (VEGF) secretion in Mos/Mps by suppressing TGFβ1 signalling and subsequently inhibits Ly6Clow Mos/Mps migration and angiogenesis. Targeted overexpression of Ep3 receptors in Mos/Mps improves wound healing by enhancing angiogenesis. Thus, the PGE2/Ep3 axis promotes cardiac healing after MI by activating reparative Ly6Clow Mos/Mps, indicating that Ep3 receptor activation may be a promising therapeutic target for acute MI. PMID:28256515

  4. Effects of specific prostanoid EP receptor agonists on cell proliferation and intracellular Ca(2+) concentrations in human airway smooth muscle cells.

    Science.gov (United States)

    Mori, Akemi; Ito, Satoru; Morioka, Masataka; Aso, Hiromichi; Kondo, Masashi; Sokabe, Masahiro; Hasegawa, Yoshinori

    2011-05-20

    Increased airway smooth muscle mass due to cell proliferation contributes to airway hyper-responsiveness and remodeling in patients with asthma. Prostaglandin E2 (PGE2) inhibits proliferation of airway smooth muscle cells, but the role of prostanoid EP receptor subtypes in mechanisms involved has not been fully elucidated yet. We investigated the effects of specific prostanoid EP receptor agonists on cell proliferation and intracellular Ca(2+) concentrations ([Ca(2+)]i) in human airway smooth muscle cells. Cell numbers were assessed by mitochondria-dependent reduction of 4-[3-(4-lodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1, 3-benzene disulfonate to formazan (WST-1 assay). RT-PCR data showed that human airway smooth muscle cells express EP2, EP3, and EP4 but not EP1 receptor mRNA. PGE2 (1nM-1μM) inhibited cell proliferation induced by 5% fetal bovine serum (FBS) in a concentration-dependent manner. (16S)-9-deoxy-9β-chloro-15-deoxy-16-hydroxy-17, 17-trimethylene-19, 20-didehydro PGE2 sodium salt (ONO-AE1-259-01; EP2 receptor agonist) and 16-(3-methoxymethyl)phenyl-ω-tetranor-3,7-dithia PGE2 (ONO-AE1-329; EP4 receptor agonist) inhibited the 5% FBS-induced cell proliferation. ONO-AE1-259-01 and ONO-AE1-329 also significantly increased the cytosolic cAMP levels. In contrast, 11,15-O-dimethyl PGE2 (ONO-AE-248; EP3 receptor agonist) elicited an oscillatory increase in [Ca(2+)]i but did not affect the cell growth or cAMP levels. [(17S)-2,5-ethano-6-oxo-17,20-dimethyl PGE1] (ONO-DI-004; EP1 receptor agonist) did not affect cell growth, cAMP levels, or [Ca(2+)]i. In conclusion, PGE2 inhibits FBS-induced cell proliferation mostly via EP2 and EP4 receptor activation and subsequent cAMP elevation. The EP3 receptor agonist causes an increase in [Ca(2+)]i without affecting cell growth. There is no functional expression of the EP1 receptor. Research on prostanoid EP receptors may lead to novel therapeutic strategies for treatment of asthma. Copyright © 2011 Elsevier B

  5. Functional pharmacological evidence for EP2 and EP4 prostanoid receptors in immortalized human trabecular meshwork and non-pigmented ciliary epithelial cells.

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    Crider, J Y; Sharif, N A

    2001-02-01

    The aim of these studies was to characterize the molecular pharmacology of the prostanoid receptors positively coupled to stimulation of adenylyl cyclase activity in immortalized human trabecular meshwork (TM-3) cells and to compare these results with that of the receptors in immortalized human nonpigmented epithelial (NPE) cells. In general, the TM-3 and NPE cells showed a similar profile with respect to their responses to various prostaglandin (PG) receptor agonists. The rank order of potency (EC50; means +/- SEM) for these compounds in the TM-3 cells was: PGE2 (124 +/- 21 nM) > 13,14-dihydro-PGE1 (430 +/- 110 nM) = PGE1 (522 +/- 345 nM) > 11-deoxy-PGE1 (1063 +/- 118 nM) = 16,16-dimethyl-PGE2 (1776 +/- 460 nM) = butaprost (1920 +/- 527 nM) > PGD2 = PGI2 = PGF2alpha (n = 3 - 12). While the agonist profile indicated the presence of EP2 receptors, the effects of the EP4 receptor antagonists suggested the additional expression of EP4 receptors in both of these cells. Thus, the EP4 receptor antagonist, AH23848B, at a concentration of 30 microM, caused a dextral shift in the PGE2 concentration-response curves in both TM-3 and NPE cells coupled with a 20-28% decrease in the maximal response of PGE2, indicating apparent noncompetitive antagonism profiles. The antagonist potency of AH23848B in these cells was: Kb = 38.4 +/- 14.8 microM and 23.5 +/- 4.5 microM; -log Kb = 4.7. The other EP4 receptor antagonist, AH22921 (-log Kb = 4.1 - 4.7), was weaker than AH23848B. Taken together, these pharmacological studies have shown than TM-3 and NPE cells apparently contain functional EP2 and EP4 prostanoid receptors positively coupled to adenylyl cyclase.

  6. Induction of cyclooxygenase-2 expression by prostaglandin E2 stimulation of the prostanoid EP4 receptor via coupling to Gαi and transactivation of the epidermal growth factor receptor in HCA-7 human colon cancer cells.

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    Yoshida, Kenji; Fujino, Hiromichi; Otake, Sho; Seira, Naofumi; Regan, John W; Murayama, Toshihiko

    2013-10-15

    Increased expressions of cyclooxygenase-2 (COX-2) and its downstream metabolite, prostaglandin E2 (PGE2), are well documented events in the development of colorectal cancer. Interestingly, PGE2 itself can induce the expression of COX-2 thereby creating the potential for positive feedback. Although evidence for such a positive feedback has been previously described, the specific E-type prostanoid (EP) receptor subtype that mediates this response, as well as the relevant signaling pathways, remain unclear. We now report that the PGE2 stimulated induction of COX-2 expression in human colon cancer HCA-7 cells is mediated by activation of the prostanoid EP4 receptor subtype and is followed by coupling of the receptor to Gαi and the activation of phosphatidylinositol 3-kinase. Subsequent activation of metalloproteinases releases membrane bound heparin-binding epidermal growth factor-like growth factor resulting in the transactivation of epidermal growth factor receptors and the activation of the extracellular signal-regulated kinases and induction of COX-2 expression. This induction of COX-2 expression by PGE2 stimulation of the prostanoid EP4 receptor may underlie the upregulation of COX-2 during colorectal cancer and appears to be an early event in the process of tumorigenesis. © 2013 Elsevier B.V. All rights reserved.

  7. Lipoic acid stimulates cAMP production via the EP2 and EP4 prostanoid receptors and inhibits IFN gamma synthesis and cellular cytotoxicity in NK cells.

    Science.gov (United States)

    Salinthone, Sonemany; Schillace, Robynn V; Marracci, Gail H; Bourdette, Dennis N; Carr, Daniel W

    2008-08-13

    The antioxidant lipoic acid (LA) treats and prevents the animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE). In an effort to understand the therapeutic potential of LA in MS, we sought to define the cellular mechanisms that mediate the effects of LA on human natural killer (NK) cells, which are important in innate immunity as the first line of defense against invading pathogens and tumor cells. We discovered that LA stimulates cAMP production in NK cells in a dose-dependent manner. Studies using pharmacological inhibitors and receptor transfection experiments indicate that LA stimulates cAMP production via activation of the EP2 and EP4 prostanoid receptors and adenylyl cyclase. In addition, LA suppressed interleukin (IL)-12/IL-18 induced IFNgamma secretion and cytotoxicity in NK cells. These novel findings suggest that LA may inhibit NK cell function via the cAMP signaling pathway.

  8. Adenylyl cyclase 2 selectively couples to E prostanoid type 2 receptors, whereas adenylyl cyclase 3 is not receptor-regulated in airway smooth muscle.

    Science.gov (United States)

    Bogard, Amy S; Adris, Piyatilake; Ostrom, Rennolds S

    2012-08-01

    Adenylyl cyclases (ACs) are important regulators of airway smooth muscle function, because β-adrenergic receptor (βAR) agonists stimulate AC activity and cAMP production. We have previously shown in a number of cell types that AC6 selectively couples to βAR and these proteins are coexpressed in lipid rafts. We overexpressed AC2, AC3, and AC6 in mouse bronchial smooth muscle cells (mBSMCs) and human embryonic kidney (HEK)-293 cells by using recombinant adenoviruses and assessed their localization and regulation by various G protein-coupled receptors (GPCRs). AC3 and AC6 were expressed primarily in caveolin-rich fractions, whereas AC2 expression was excluded from these domains. AC6 expression enhanced cAMP production in response to isoproterenol but did not increase responses to butaprost, reflecting the colocalization of AC6 with β(2)AR but not E prostanoid type 2 receptor (EP(2)R) in lipid raft fractions. AC2 expression enhanced butaprost-stimulated cAMP production but had no effect on the β(2)AR-mediated response. AC3 did not couple to any GPCR tested. Forskolin-induced arborization of mBSMCs was assessed as a functional readout of cAMP signaling. Arborization was enhanced by overexpression of AC6 and AC3, but AC2 had no effect. GPCR-stimulated arborization mirrored the selective coupling observed for cAMP production. With the addition of the phosphodiesterase 4 (PDE4) inhibitor rolipram AC2 accelerated forskolin-stimulated arborization. Thus, AC2 selectively couples to EP(2)R, but signals from this complex are limited by PDE4 activity. AC3 does not seem to couple to GPCR in either mBSMCs or HEK-293 cells, so it probably exists in a distinct signaling domain in these cells.

  9. Detection of EP1 and FP receptor mRNAs in the iris-ciliary body using in situ hybridization%用原位杂交方法检测虹膜睫状体EP1和FP受体mRNA的表达

    Institute of Scientific and Technical Information of China (English)

    张振平; 印湖莲

    2002-01-01

    Objective To determine the expression of E-prostanoid1 (EP1) and F-prostanoid (FP) receptor mRNAs in iris-ciliary bodies of the human eye using in situ hybridization.Methods EP1 and FP receptor mRNAs were detected by riboprobes labeled with digoxigenin on paraffin sections of the iris-ciliary body tissue of the human eye using in situ hybridization. Results EP1 and FP receptor mRNAs were highly expressed in blood vessels, muscles and the endothelia of the iris. EP1 receptor hybridization signals were present in all muscle fibers of the ciliary body. Hybridization signal corresponding to FP receptor mRNA transcript was predominantly expressed in the circular muscle and in the collagenous connective tissues of the ciliary body. FP receptor mRNA was not detected in radial and longitudinal muscles. Conclusions EP1 and FP receptor mRNAs in human ocular tissues appear to be widely localized in the functional sites of the respective receptor agonists. Selective localization of EP1 and FP receptor mRNAs in the circular muscles and collagenous connective tissues of the ciliary body suggests that EP1 and FP receptors play an important role in enhancing uveoscleral outflow of aqueous humor.%目的检测人眼虹膜-睫状体组织内EP1和FP受体mRNA的表达情况.方法以地高辛标记EP1和FP受体探针,用原位杂交方法检测人眼石蜡切片虹膜-睫状体相应受体mRNA的信号表达.结果虹膜的血管、肌肉和内皮层见大量EP1和FP受体mRNA表达.EP1受体mRNA信号见于睫状体所有的肌肉纤维;FP受体杂交信号主要见于睫状体环形肌肉和结缔组织,纵行肌和放射状肌肉的信号未能检测到.结论人眼组织EP1和FP受体mRNA广泛表达于相应有关受体激动剂作用的功能部位.EP1和FP受体mRNA选择性的表达于睫状体环形肌和结缔组织,提示二种受体在增加巩膜脉络膜房水引流过程中起着重要作用.

  10. Possible involvement of brain prostaglandin E2 and prostanoid EP3 receptors in prostaglandin E2 glycerol ester-induced activation of central sympathetic outflow in the rat.

    Science.gov (United States)

    Shimizu, Takahiro; Tanaka, Kenjiro; Nakamura, Kumiko; Taniuchi, Keisuke; Yawata, Toshio; Higashi, Youichirou; Ueba, Tetsuya; Dimitriadis, Fotios; Shimizu, Shogo; Yokotani, Kunihiko; Saito, Motoaki

    2014-07-01

    We recently reported that intracerebroventricularly administered 2-arachidonoylglycerol elevated plasma noradrenaline and adrenaline by brain monoacylglycerol lipase- (MGL) and cyclooxygenase-mediated mechanisms in the rat. These results suggest that 2-arachidonoylglycerol is hydrolyzed by MGL to free arachidonic acid, which is further metabolized to prostaglandins (PGs) by cyclooxygenase in the brain, thereby elevating plasma noradrenaline and adrenaline. On the other hand, 2-arachidonoylglycerol can be also metabolized by cyclooxygenase to PG glycerol esters (PG-Gs), which seems to be hydrolyzed by MGL to free PGs. Here, we examined the involvement of brain PG-Gs in the elevation of plasma noradrenaline and adrenaline regarding PGE2-G and prostanoid EP receptors using anesthetized male Wistar rats. Intracerebroventricularly administered PGE2-G (1.5 and 3 nmol/animal) dose-dependently elevated plasma noradrenaline but not adrenaline. PGE2-G also elevated systolic, mean and diastolic blood pressure and heart rate. The PGE2-G-induced elevation of plasma noradrenaline was attenuated by JZL184 (MGL inhibitor). Intracerebroventricularly administered PGE2 (0.3 and 1.5 nmol/animal) and sulprostone (0.1 and 0.3 nmol/animal) (EP1/EP3 agonist) also elevated plasma noradrenaline but not adrenaline in a dose-dependent manner. The sulprostone-induced elevation was attenuated by L-798,106 (EP3 antagonist), but not by SC-51322 (EP1 antagonist). L-798,106 also attenuated the PGE2-G- and PGE2-induced elevation of plasma noradrenaline, while PF-04418948 (EP2 antagonist) and L-161,982 (EP4 antagonist) had no effect on the PGE2-G-induced response. These results suggest a possibility that brain PGE2-G produced from 2-arachidonoylglycerol can be hydrolyzed to free PGE2, thereby activating central sympathetic outflow by brain prostanoid EP3 receptor-mediated mechanisms in the rat. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Selective activation of E-type prostanoid(3)-receptors reduces myocardial infarct size. A novel insight into the cardioprotective effects of prostaglandins.

    Science.gov (United States)

    Thiemermann, C; Zacharowski, K

    2000-07-01

    Prostaglandins (PGs) and other eicosanoids are members of a large family of lipid mediators (autacoids). In 1978, Lefer and colleagues (Science 200, 52-55 [1978]) reported that prostacyclin reduces the myocardial tissue injury caused by coronary artery occlusion and reperfusion in the cat. Since this discovery, more than 50 papers have reported on the cardioprotective effects of vasodilator PGs, including prostacyclin. The cardioprotective effects of PGs are due in part to (1) a reduction in afterload, (2) an increase in coronary blood flow, (3) the inhibition of platelet function, and (4) the inhibition of the activation and extravasation of polymorphonuclear granulocytes. All of these effects are secondary to the activation of EP (E-type prostanoid)(2)-receptors, which activate G(s)-protein and, hence, adenylate cyclase. In addition, the protection of organs such as the heart by PGs has been attributed to a cytoprotective effect of these agents, the mechanism of which is largely unknown. We recently have discovered that certain E-type PGs, which do not activate EP(2)-receptors, also reduce myocardial infarct size, without causing a fall in blood pressure (EP(2)-receptor-mediated effects). Having provided a brief introduction into the role of eicosanoids in ischaemia-reperfusion injury of the heart, this review focuses on the recent discovery that selective agonists of EP(3)-receptors reduce myocardial infarct size, without causing haemodynamic side effects. The mechanisms of the cardioprotective effects of these agents are discussed, as are the therapeutic implications.

  12. Host knockout of E-prostanoid 2 receptors reduces tumor growth and causes major alterations of gene expression in prostaglandin E2-producing tumors

    Science.gov (United States)

    Asting, Annika Gustafsson; Iresjö, Britt-Marie; Nilsberth, Camilla; Smedh, Ulrika; Lundholm, Kent

    2017-01-01

    Prostaglandin E2 (PGE2) is elevated in a variety of malignant tumors and has been shown to affect several hallmarks of cancer. Accordingly, the PGE2 receptor, E-prostanoid 2 (EP2), has been reported to be associated with patient survival and reduced tumor growth in EP2-knockout mice. Thus, the aim of the present study was to screen for major gene expression alterations in tumor tissue growing in EP2-knockout mice. EP2-knockout mice were bred and implanted with EP2 receptor-expressing and PGE2-producing epithelial-like tumors. Tumor tissue and plasma were collected and used for analyses with gene expression microarrays and multiplex enzyme-linked immunosorbent assays. Tumor growth, acute phase reactions/systemic inflammation and the expression of interleukin-6 were reduced in EP2-knockout tumor-bearing mice. Several hundreds of genes displayed major changes of expression in the tumor tissue when grown in EP2-knockout mice. Such gene alterations involved several different cellular functions, including stemness, migration and cell signaling. Besides gene expression, several long non-coding RNAs were downregulated in the tumors from the EP2-knockout mice. Overall, PGE2 signaling via host EP2 receptors affected a large number of different genes involved in tumor progression based on signaling between host stroma and tumor cells, which caused reduced tumor growth. PMID:28123585

  13. Lipidomic analysis reveals prostanoid profiles in human term pregnant myometrium.

    Science.gov (United States)

    Durn, J H; Marshall, K M; Farrar, D; O'Donovan, P; Scally, A J; Woodward, D F; Nicolaou, A

    2010-01-01

    Prostanoids modulate the activity of human pregnant myometrium and their functional role can be appreciated through characterisation of prostanoid receptors and tissue concentration of prostanoids. We have applied a lipidomic approach to elucidate the profile of prostanoids in human non-labouring and labouring myometrium. We have identified a total of nineteen prostanoids including prostacyclin, thromboxanes, prostaglandins and dihydro-prostaglandins. Prostacyclin was the predominant prostanoid in both non-labouring and labouring myometria, with PGD(2) and PGF(2alpha) being the second most abundant. Although the total amount of prostanoids was increased in the labouring tissue, PGE(2) and 13,14-dihydro-15-keto-PGE(2) were the only prostanoids to increase significantly at early and late labour (pincrease in PGE(2) could occur to facilitate cervical dilation and relaxation of the lower myometrium during labour. Although the elevation in TXA(2) was less marked than expected, in terms of translation to function even a relatively small increase in the level of this potent spasmogen may have significant effects. Copyright 2009 Elsevier Ltd. All rights reserved.

  14. PGE2 upregulates renin through E-prostanoid receptor 1 via PKC/cAMP/CREB pathway in M-1 Cells.

    Science.gov (United States)

    Gonzalez, Alexis A; Salinas-Parra, Nicolas; Leach, Dan; Navar, L Gabriel; Prieto, Minolfa C

    2017-07-12

    During the early phase of angiotensin (ANG) II-dependent hypertension tubular prostaglandin E2 (PGE2) is increased. Renin synthesis and secretion in the collecting duct (CD) is upregulated by ANGII contributing to further intratubular ANGII formation. However, what happens first and whether the triggering mechanism is independent of tubular ANGII, remain unknown. PGE2 stimulates renin synthesis in juxtaglomerular (JG) cells via E-prostanoid (EP) receptors through cAMP/CREB pathway. EP receptors are also expressed in the CD. Here, we tested the hypothesis that renin is upregulated by PGE2 in CD cells. M-1 CD cell line expressed EP1, EP3 and EP4 but not EP2. Dose response experiments in the presence of AT1 receptor blockade with candesartan demonstrated that 10-6 M PGE2 maximally increases renin mRNA (~4 fold) and prorenin/renin protein levels (~2 fold). This response was prevented by micromolar doses of SC-19220 (EP1 antagonist), attenuated by the EP4 antagonist, L-161,982, and exacerbated by the highly selective EP3 antagonist, L-798106 (~10 fold increase). To further evaluate the signaling pathway involved we used the PKC inhibitor calphostin C and transfections with PKCα dominant negative (DN). Both strategies blunted the PGE2-induced increases in cAMP levels, CREB phosphorylation and augmentation of renin. Knockdown of EP1 receptor and CREB also prevented renin upregulation. These results indicate that PGE2 increases CD renin expression through EP1 receptor via PKC/cAMP/CREB pathway. Therefore, we conclude that during early stages of ANGII-dependent hypertension, there is augmentation of PGE2 that stimulates renin in the CD, resulting in increased tubular ANGII formation and further stimulation of renin. Copyright © 2017, American Journal of Physiology-Renal Physiology.

  15. Prostaglandin (PG) FP and EP1 receptors mediate PGF2alpha and PGE2 regulation of interleukin-1beta expression in Leydig cell progenitors.

    Science.gov (United States)

    Walch, Laurence; Clavarino, Emanuela; Morris, Patricia L

    2003-04-01

    Prostaglandins (PG) mediate IL-1beta regulation of several interleukin mRNAs in progenitor Leydig cells. PGE(2) and PGF(2alpha) potently reverse indomethacin (INDO; a cyclooxygenase inhibitor) inhibition of IL-1beta autoinduction. IL-1beta increases PGE(2) and PGF(2alpha) production. To determine the PG receptors involved in this regulation, this study established by RT-PCR and Western analyses which specific receptors for PGE(2) (EP receptors) and PGF(2alpha) (FP receptors) are expressed in progenitors. Pharmacological characterization of receptors involved in PGE(2) and PGF(2alpha) regulation of IL-1beta mRNA levels was ascertained using real-time PCR analyses. FP, EP(1), EP(2), and EP(4) receptor mRNAs and proteins, and an EP(3) receptor subtype were detected. IL-1beta treatment (24-h) significantly decreased EP(1) receptor levels; INDO abrogated this down-regulation. FP, EP(2), and EP(4) receptor levels increased after IL-1beta and IL-1beta + INDO. A selective FP agonist, cloprostenol (0.1 micro M), and PGF(2alpha) (10 micro M) had similar effects on IL-1beta mRNA levels in progenitors treated with IL-1beta + INDO. None of the EP(2)/EP(4) agonists [butaprost, misoprostol, or 11-deoxy PGE(1) (10 micro M)] affected IL-1beta mRNA levels. In contrast, EP(1)/EP(3) agonists (17-phenyl trinor PGE(2) and sulprostone) increased IL-1beta mRNAs in a dose-dependent manner. EP(1) receptor subtype-selective antagonist, SC-51322, blocked IL-1beta-induced and [IL-1beta + INDO + 17-phenyl trinor PGE(2)]-induced increases in IL-1beta mRNAs. Taken together, our data demonstrate that FP and EP(1) receptors mediate PGF(2alpha) and PGE(2) induction of progenitor IL-1beta expression.

  16. Differential regulation of phosphorylation of the cAMP response element-binding protein after activation of EP2 and EP4 prostanoid receptors by prostaglandin E2.

    Science.gov (United States)

    Fujino, Hiromichi; Salvi, Sambhitab; Regan, John W

    2005-07-01

    The EP2 and EP4 prostanoid receptors are G-protein-coupled receptors whose activation by their endogenous ligand, prostaglandin (PG) E2, stimulates the formation of intracellular cAMP. We have previously reported that the stimulation of cAMP formation in EP4-expressing cells is significantly less than in EP2-expressing cells, despite nearly identical levels of receptor expression (J Biol Chem 277:2614-2619, 2002). In addition, a component of EP4 receptor signaling, but not of EP2 receptor signaling, was found to involve the activation of phosphatidylinositol 3-kinase (PI3K). In this study, we report that PGE2 stimulation of cells expressing either the EP2 or EP4 receptor results in the phosphorylation of the cAMP response element binding protein (CREB) at serine-133. Pretreatment of cells with N-[2-(4-bromocinnamylamino)ethyl]-5-isoquinoline (H-89), an inhibitor of protein kinase A (PKA), attenuated the PGE2-mediated phosphorylation of CREB in EP2-expressing cells, but not in EP4-expressing cells. Pretreatment of cells with wortmannin, an inhibitor of PI3K, had no effects on the PGE2-mediated phosphorylation of CREB in either EP2- or EP4-expressing cells, although it significantly increased the PGE2-mediated activation of PKA in EP4-expressing cells. However, combined pretreatment with H-89 and wortmannin blocked PGE2-mediated phosphorylation in EP2-expressing cells as well as in EP2-expressing cells. PGE2-mediated intracellular cAMP formation was not affected by pretreatment with wortmannin, or combined treatment with wortmannin and H-89, in either the EP2- or EP4-expressing cells. These findings suggest that PGE2 stimulation of EP4 receptors, but not EP2 receptors, results in the activation of a PI3K signaling pathway that inhibits the activity of PKA and that the PGE2-mediated phosphorylation of CREB by these receptors occurs through different signaling pathways

  17. Cyclooxygenase-2, prostaglandin E2, and prostanoid receptor EP2 in fluid flow shear stress-mediated injury in the solitary kidney.

    Science.gov (United States)

    Srivastava, Tarak; Alon, Uri S; Cudmore, Patricia A; Tarakji, Belal; Kats, Alexander; Garola, Robert E; Duncan, R Scott; McCarthy, Ellen T; Sharma, Ram; Johnson, Mark L; Bonewald, Lynda F; El-Meanawy, Ashraf; Savin, Virginia J; Sharma, Mukut

    2014-12-15

    Hyperfiltration subjects podocytes to increased tensile stress and fluid flow shear stress (FFSS). We showed a 1.5- to 2.0-fold increase in FFSS in uninephrectomized animals and altered podocyte actin cytoskeleton and increased synthesis of prostaglandin E2 (PGE2) following in vitro application of FFSS. We hypothesized that increased FFSS mediates cellular changes through specific receptors of PGE2. Presently, we studied the effect of FFSS on cultured podocytes and decapsulated isolated glomeruli in vitro, and on solitary kidney in uninephrectomized sv129 mice. In cultured podocytes, FFSS resulted in increased gene and protein expression of cyclooxygenase (COX)-2 but not COX-1, prostanoid receptor EP2 but not EP4, and increased synthesis and secretion of PGE2, which were effectively blocked by indomethacin. Next, we developed a special flow chamber for applying FFSS to isolated glomeruli to determine its effect on an intact glomerular filtration barrier by measuring change in albumin permeability (Palb) in vitro. FFSS caused an increase in Palb that was blocked by indomethacin (P < 0.001). Finally, we show that unilateral nephrectomy in sv129 mice resulted in glomerular hypertrophy (P = 0.006), increased glomerular expression of COX-2 (P < 0.001) and EP2 (P = 0.039), and increased urinary albumin excretion (P = 0.001). Activation of the COX-2-PGE2-EP2 axis appears to be a specific response to FFSS in podocytes and provides a mechanistic basis for alteration in podocyte structure and the glomerular filtration barrier, leading to albuminuria in hyperfiltration-mediated kidney injury. The COX-2-PGE2-EP2 axis is a potential target for developing specific interventions to ameliorate the effects of hyperfiltration-mediated kidney injury in the progression of chronic kidney disease.

  18. An important role of prostanoid receptor EP2 in host resistance to Mycobacterium tuberculosis infection in mice.

    Science.gov (United States)

    Kaul, Vandana; Bhattacharya, Debapriya; Singh, Yogesh; Van Kaer, Luc; Peters-Golden, Marc; Bishai, William R; Das, Gobardhan

    2012-12-15

    Mycobacterium tuberculosis, the causative agent of tuberculosis, resides and replicates within susceptible hosts by inhibiting host antimicrobial mechanisms. Prostaglandin E(2) (PGE(2)), produced by M. tuberculosis-infected macrophages, exerts a variety of immunomodulatory functions via 4 receptors (EP1-EP4), each mediating distinct PGE(2) functions. Here, we show that M. tuberculosis infection selectively upregulates EP2 messenger RNA expression in CD4(+) T cells. We found that EP2 deficiency in mice increases susceptibility to M. tuberculosis infection, which correlated with reduced antigen-specific T-cell responses and increased levels of CD4(+)CD25(+)Foxp3(+) T-regulatory cells. These findings have revealed an important role for EP2 in host immune defense against tuberculosis. As a G protein-coupled receptor, EP2 could serve as a target for immunotherapy of tuberculosis.

  19. Detrimental role of the EP1 prostanoid receptor in blood-brain barrier damage following experimental ischemic stroke.

    Science.gov (United States)

    Frankowski, Jan C; DeMars, Kelly M; Ahmad, Abdullah S; Hawkins, Kimberly E; Yang, Changjun; Leclerc, Jenna L; Doré, Sylvain; Candelario-Jalil, Eduardo

    2015-12-09

    Cyclooxygenase-2 (COX-2) is activated in response to ischemia and significantly contributes to the neuroinflammatory process. Accumulation of COX-2-derived prostaglandin E2 (PGE2) parallels the substantial increase in stroke-mediated blood-brain barrier (BBB) breakdown. Disruption of the BBB is a serious consequence of ischemic stroke, and is mainly mediated by matrix metalloproteinases (MMPs). This study aimed to investigate the role of PGE2 EP1 receptor in neurovascular injury in stroke. We hypothesized that pharmacological blockade or genetic deletion of EP1 protects against BBB damage and hemorrhagic transformation by decreasing the levels and activity of MMP-3 and MMP-9. We found that post-ischemic treatment with the EP1 antagonist, SC-51089, or EP1 genetic deletion results in a significant reduction in BBB disruption and reduced hemorrhagic transformation in an experimental model of transient focal cerebral ischemia. These neurovascular protective effects of EP1 inactivation are associated with a significant reduction in MMP-9/-3, less peripheral neutrophil infiltration, and a preservation of tight junction proteins (ZO-1 and occludin) composing the BBB. Our study identifies the EP1 signaling pathway as an important link between neuroinflammation and MMP-mediated BBB breakdown in ischemic stroke. Targeting the EP1 receptor could represent a novel approach to diminish the devastating consequences of stroke-induced neurovascular damage.

  20. Prostanoid EP1 receptors mediate up-regulation of the orphan nuclear receptor Nurr1 by cAMP-independent activation of protein kinase A, CREB and NF-κB

    Science.gov (United States)

    Ji, R; Sanchez, CM; Chou, CL; Chen, XB; Woodward, DF; Regan, JW

    2012-01-01

    BACKGROUND AND PURPOSE Prostaglandin E2 (PGE2) stimulation of the G protein-coupled prostanoid EP1 receptor was found to up-regulate the expression of Nur-related factor 1 (Nurr1) (NR4A2), a transcription factor in the NR4A subfamily of nuclear receptors. The present studies characterize the molecular mechanism of this up-regulation. EXPERIMENTAL APPROACH The expression of Nurr1 was examined by immunoblot analysis, the polymerase chain reaction and reporter gene assays in human embryonic kidney (HEK) cells stably expressing the recombinant EP1 receptor and in SH-SY5Y neuroblastoma cells expressing endogenous EP1 receptors. Signalling pathway inhibitors were used to examine the roles of Rho, PKA, the cAMP response element binding protein (CREB) and NF-κB on the PGE2 stimulated up-regulation of Nurr1. CREB and NF-κB signalling were also examined by immunoblot analysis and reporter gene assays. KEY RESULTS The EP1 receptor mediated up-regulation of Nurr1 was blocked with inhibitors of Rho, PKA, NF-κB and CREB; but PGE2 failed to significantly stimulate intracellular cAMP formation. PGE2 stimulation of the EP1 receptor induced the phosphorylation and activation of CREB and NF-κB, which could be blocked by inhibition of PKA. CONCLUSIONS AND IMPLICATIONS PGE2 stimulation of the human EP1 receptor up-regulates the expression of Nurr1 by a mechanism involving the sequential activation of the Rho, PKA, CREB and NF-κB signalling pathways. EP1 receptors are implicated in tumorigenesis and the up-regulation of Nurr1 may underlie the anti-apoptotic effects of PGE2. PMID:22188298

  1. Expression of prostaglandin E2 prostanoid receptor EP2 and interleukin-1β in laryngeal carcinoma – preliminary study

    Science.gov (United States)

    Mochocki, Marcin; Morawski, Piotr; Kopta, Renata; Brzezińska-Błaszczyk, Ewa; Stasikowska, Olga; Lewy-Trenda, Iwona

    2015-01-01

    Aim of the study Expression of EP2 protein, the prostaglandin E2 (PGE2) receptor, produced by tumour microenvironment inflammatory cells as well as tumour cells, may promote cellular proliferation and growth in an autocrine and paracrine fashion. The phenomenon involving these proteins is regulated by interleukin 1β (IL-1β). Many researchers indicate a connection of EP2 and IL-1β in various types of neoplasms with higher tumour progression and poor prognosis. The aim of this study was to analyse the EP2 expression within laryngeal carcinoma tissue and IL-1β levels in peripheral blood mononuclear cell supernatants and to find relationships between clinicomorphological features. Material and methods A group of 50 patients with verified squamous cell laryngeal carcinoma was analysed in this study. The pathological evaluation included pTNM depth of invasion according to tumour front grading criteria. Immunohistochemical analysis for membranous staining of EP2 in tumour tissues was used. The IL-1β expression was determined by enzyme-linked immunosorbent assay (ELISA). Results Increased EP2 expression in carcinoma cells was confirmed for more advanced tumours (pT3-pT4 vs. pT1-pT2, p < 0.0001 and pN1-3 vs. pN0, p = 0.02). Tumours with the highest aggressiveness identified by deeper invasion of submucosa or cartilage were characterised by the highest expression of EP2 (p < 0.0001). In laryngeal carcinomas characterised by a lower differentiation the highest EP2 expression in tumour cells was noted (p = 0.009). A positive relationship between IL-1β expression and the presence of lymph node metastases was also confirmed (p = 0.04). Conclusions The study indicates the potential effect of EP2 receptor and IL-1β on tumour progression in laryngeal carcinoma. PMID:26034388

  2. Molecular Characterization of E-Type Prostanoid Receptor 4 (EP4 from Ayu (Plecoglossus altivelis and Its Functional Analysis in the Monocytes/Macrophages.

    Directory of Open Access Journals (Sweden)

    Ye-Jing Rong

    Full Text Available Prostaglandin E2 (PGE2 plays an important role in a broad spectrum of physiological and pathological processes by interacting with E-type prostanoid receptors (EPs. EP4 is one of four EP subtypes known to mediate the immune response in mammalian monocytes/macrophages. However, the precise function and characteristics of EP4 in fish remain unclear. In this study, we characterized a novel EP4-like (PaEP4L gene from ayu, Plecoglossus altivelis. The cDNA sequence of PaEP4L is 2781 nucleotides (nts in length, encoding a polypeptide of 459 amino acid residues with a calculated molecular weight of 51.17 kDa. Sequence comparison and phylogenetic tree analysis showed that PaEP4L shared 76% amino acid identity with that of the Atlantic salmon (Salmo salar. PaEP4L mRNA was detected by real-time quantitative PCR (QPCR in all tested tissues and head kidney-derived monocytes/macrophages (MO/MФ. It varied greatly in liver, spleen and MO/MФ upon Vibrio anguillarum infection. Western blot analysis revealed a significant increase of PaEP4L in cell homogenates from ayu MO/MФ upon V. anguillarum infection. Moreover, anti-PaEP4L IgG reversed the down-regulation of interleukin 1β (IL-1β and tumor necrosis factor α (TNF-α mRNA expression as well as phagocytosis in ayu MO/MФ caused by PGE2. There were no significant differences in the respiratory burst response between PGE2 treated and untreated cells. We further found that cAMP mediated PGE2/PaEP4L signal in ayu MO/MФ. In conclusion, our results indicate that PaEP4L mediates PGE2 effects on ayu MO/MФ function, revealing that EP4 also plays a role in the modulation of cells of the fish's innate immune system.

  3. Cyclic Codes over Fp + uFp + vFp + uvFp%环Fp+uFp+vFp+uvFp上的循环码

    Institute of Scientific and Technical Information of China (English)

    许小芳; 刘修生

    2013-01-01

    In this paper,cyclic codes over the ring R =Fp + uFp + vFp + uvFp arediscussed,where the ring R is not afinite chain ring.By studying the polynomial ring Rn =(Fp + uFp + vFp + uvFp,) [x]/(xn-1) and using the corresponding relationship between the cyclic codes over the ring R and the ideals in the ringRn,cyclic codes over the ring R are characterized.Finally,a Gray-map is obtained and the images of cyclic codes over the ring R are characterized.%讨论了非有限链环R=Fp+uFp+vFp+uvFp上的循环码.通过环R上的循环码与多项式环Rn=(Fp+uFp+vFp+uvFp)[x]/(xn-1)的理想的对应关系及对Rn的研究给出了R上循环码的刻画.最后定义了一个Gray映射,并刻画了Fp+uFp+vFp+uvFp上的循环码在该映射下的像.

  4. EP1 Prostanoid Receptor Coupling to Gi/o Up-Regulates the Expression of Hypoxia-Inducible Factor-1α through Activation of a Phosphoinositide-3 Kinase Signaling Pathway

    Science.gov (United States)

    Ji, Ruyue; Chou, Chih-Ling; Xu, Wei; Chen, Xiao-Bo; Woodward, David F.

    2010-01-01

    The EP1 prostanoid receptor is one of four subtypes whose cognate physiological ligand is prostaglandin-E2 (PGE2). It is in the family of G-protein-coupled receptors and is known to activate Ca2+ signaling, although relatively little is known about other aspects of E-type prostanoid receptor (EP) 1 receptor signaling. In human embryonic kidney (HEK) cells expressing human EP1 receptors, we now show that PGE2 stimulation of the EP1 receptor up-regulates the expression of hypoxia-inducible factor-1α (HIF-1α), which can be completely blocked by pertussis toxin, indicating coupling to Gi/o. This up-regulation of HIF-1α occurs under normoxic conditions and could be inhibited with wortmannin, Akt inhibitor, and rapamycin, consistent with the activation of a phosphoinositide-3 kinase/Akt/mammalian target of rapamycin (mTOR) signaling pathway, respectively. In contrast to the hypoxia-induced up-regulation of HIF-1α, which involves decreased protein degradation, the up-regulation of HIF-1α by the EP1 receptor was associated with the phosphorylation of ribosomal protein S6 (rpS6), suggesting activation of the ribosomal S6 kinases and increased translation. Stimulation of endogenous EP1 receptors in human HepG2 hepatocellular carcinoma cells recapitulated the normoxic up-regulation of HIF-1α observed in HEK cells, was sensitive to pertussis toxin, and involved the activation of mTOR signaling and phosphorylation of rpS6. In addition, treatment of HepG2 cells with sulprostone, an EP1-selective agonist, up-regulated the mRNA expression of vascular endothelial growth factor-C, a HIF-regulated gene. HIF-1α is known to promote tumor growth and metastasis and is often up-regulated in cancer. Our findings provide a potential mechanism by which increased PGE2 biosynthesis could up-regulate the expression of HIF-1α and promote tumorigenesis. PMID:20335389

  5. Low E-prostanoid 2 receptor levels and deficient induction of the IL-1β/IL-1 type I receptor/COX-2 pathway: Vicious circle in patients with aspirin-exacerbated respiratory disease.

    Science.gov (United States)

    Machado-Carvalho, Liliana; Martín, Margarita; Torres, Rosa; Gabasa, Marta; Alobid, Isam; Mullol, Joaquim; Pujols, Laura; Roca-Ferrer, Jordi; Picado, Cesar

    2016-01-01

    We hypothesized that the 2 reported alterations in aspirin-exacerbated respiratory disease (AERD), reduced expression/production of COX-2/prostaglandin (PG) E2 and diminished expression of E-prostanoid (EP) 2 receptor, are closely linked. We sought to determine the mechanisms involved in the altered regulation of the COX pathway in patients with AERD. Fibroblasts were obtained from nasal mucosa; samples of control subjects (NM-C, n = 8) and from nasal polyps from patients with aspirin-exacerbated respiratory disease (NP-AERD, n = 8). Expression of the autocrine loop components regulating PGE2 production and signaling, namely IL-1 type I receptor (IL-1RI), COX-2, microsomal prostaglandin E synthase 1 (mPGES-1), and EP receptors, was assessed at baseline and after stimulation with IL-1β, PGE2, and specific EP receptor agonists. Compared with NM-C fibroblasts, basal expression levels of IL-1RI and EP2 receptor were lower in NP-AERD fibroblasts. IL-1β-induced IL-1RI, COX-2, and mPGES-1 expression levels were also lower in these cells. Levels of IL-1RI positively correlated with COX-2 and mPGES-1 expression in both NM-C and NP-AERD fibroblasts. Incubation with either exogenous PGE2 or selective EP2 agonist significantly increased expression of IL-1RI in NM-C fibroblasts and had hardly any effect on NP-AERD fibroblasts. Alterations in IL-1RI, COX-2, and mPGES-1 expression that were found in NP-AERD fibroblasts were corrected when EP2 receptor expression was normalized by transfection of NP-AERD fibroblasts. Altered expression of EP2 in patients with AERD contributes to deficient induction of IL-1RI, reducing the capacity of IL-1β to increase COX-2 and mPGES-1 expression, which results in low PGE2 production. This impairment in the generation of PGE2 subsequently reduces its ability to induce IL-1RI. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  6. Epigenetic Regulations of Inflammatory Cyclooxygenase-Derived Prostanoids: Molecular Basis and Pathophysiological Consequences

    Directory of Open Access Journals (Sweden)

    Hedi Harizi

    2015-01-01

    Full Text Available The potential relevance of prostanoid signaling in immunity and immunological disorders, or disease susceptibility and individual variations in drug responses, is an important area for investigation. The deregulation of Cyclooxygenase- (COX- derived prostanoids has been reported in several immunoinflammatory disorders such as asthma, rheumatoid arthritis, cancer, and autoimmune diseases. In addition to the environmental factors and the genetic background to diseases, epigenetic mechanisms involved in the fine regulation of prostanoid biosynthesis and/or receptor signaling appeared to be an additional level of complexity in the understanding of prostanoid biology and crucial in controlling the different components of the COX pathways. Epigenetic alterations targeting inflammatory components of prostanoid biosynthesis and signaling pathways may be important in the process of neoplasia, depending on the tissue microenvironment and target genes. Here, we focused on the epigenetic modifications of inflammatory prostanoids in physiological immune response and immunological disorders. We described how major prostanoids and their receptors can be functionally regulated epigenetically and consequently the impact of these processes in the pathogenesis inflammatory diseases and the development of therapeutic approaches that may have important clinical applications.

  7. Leukotriene D4 and prostaglandin E2 signals synergize and potentiate vascular inflammation in a mast cell-dependent manner through cysteinyl leukotriene receptor 1 and E-prostanoid receptor 3.

    Science.gov (United States)

    Kondeti, Vinay; Al-Azzam, Nosayba; Duah, Ernest; Thodeti, Charles K; Boyce, Joshua A; Paruchuri, Sailaja

    2016-01-01

    Although arachidonic acid metabolites, cysteinyl leukotrienes (cys-LTs; leukotriene [LT] C4, LTD4, and LTE4), and prostaglandin (PG) E2 are generated at the site of inflammation, it is not known whether crosstalk exists between these 2 classes of inflammatory mediators. We sought to determine the role of LTD4-PGE2 crosstalk in inducing vascular inflammation in vivo, identify effector cells, and ascertain specific receptors and pathways involved in vitro. Vascular (ear) inflammation was assessed by injecting agonists into mouse ears, followed by measuring ear thickness and histology, calcium influx with Fura-2, phosphorylation and expression of signaling molecules by means of immunoblotting, PGD2 and macrophage inflammatory protein 1β generation by using ELISA, and expression of transcripts by using RT-PCR. Candidate receptors and signaling molecules were identified by using antagonists and inhibitors and confirmed by using small interfering RNA. LTD4 plus PGE2 potentiated vascular permeability and edema, gearing the system toward proinflammation in wild-type mice but not in Kit(W-sh) mice. Furthermore, LTD4 plus PGE2, through cysteinyl leukotriene receptor 1 (CysLT1R) and E-prostanoid receptor (EP) 3, enhanced extracellular signal-regulated kinase (Erk) and c-fos phosphorylation, inflammatory gene expression, macrophage inflammatory protein 1β secretion, COX-2 upregulation, and PGD2 generation in mast cells. Additionally, we uncovered that this synergism is mediated through Gi, protein kinase G, and Erk signaling. LTD4 plus PGE2-potentiated effects are partially sensitive to CysLT1R or EP3 antagonists but completely abolished by simultaneous treatment both in vitro and in vivo. Our results unravel a unique LTD4-PGE2 interaction affecting mast cells through CysLT1R and EP3 involving Gi, protein kinase G, and Erk and contributing to vascular inflammation in vivo. Furthermore, current results also suggest an advantage of targeting both CysLT1R and EP3 in

  8. Inhibition by prostaglandin E(2) of anaphylatoxin C5a- but not zymosan-induced prostanoid release from rat Kupffer cells.

    Science.gov (United States)

    Pestel, Sabine; Jungermann, Kurt; Götze, Otto; Schieferdecker, Henrike L

    2002-04-01

    The proinflammatory anaphylatoxin C5a induces the release of prostanoids, ie, prostaglandins (PG) and thromboxane (TX), from the resident liver macrophages (Kupffer cells [KC]). Because KC themselves express prostanoid receptors, prostanoids--besides having paracrine functions--might regulate their own release in an autocrine loop. So far, such a possible feedback regulation has not been investigated systematically, probably because of methodological difficulties to measure newly synthesized prostanoids in the presence of added prostanoids. Here, after prelabeling of phospholipids with [(14)C]arachidonate, cellularly formed [(14)C]prostanoids were determined in the presence of added unlabelled prostanoids by thin layer chromatography. In cultured KC, recombinant rat C5a (rrC5a) rapidly increased PGD(2), PGE(2), and TXA(2) release, which was strongly reduced by PGE(2), but neither by PGD(2) nor by the TXA(2) analog U46619. The inhibitory effect of PGE(2) was mimicked by cAMP, indicating that the G(s)-coupled PGE(2) receptors type 2 or 4 were involved. Zymosan also enhanced prostanoid release from KC, but with slightly slower kinetics; this action was neither inhibited by PGE(2) nor by cAMP. Also in perfused rat livers, rrC5a enhanced prostanoid release from KC as shown by prostanoid overflow and thereby indirectly increased glucose output from hepatocytes. Again, PGE(2), but not PGD(2), inhibited rrC5a-elicited prostanoid overflow. This resulted in a complete inhibition of rrC5a-induced, prostanoid-mediated glucose output. Thus, PGE(2) can inhibit specifically the C5a-induced prostanoid release from KC via a feedback mechanism and thereby limit prostanoid-mediated hepatocellular defense reactions, eg, glucose release.

  9. Mechanism of prostaglandin (PG)E2-induced prolactin expression in human T cells: cooperation of two PGE2 receptor subtypes, E-prostanoid (EP) 3 and EP4, via calcium- and cyclic adenosine 5'-monophosphate-mediated signaling pathways.

    Science.gov (United States)

    Gerlo, Sarah; Verdood, Peggy; Gellersen, Birgit; Hooghe-Peters, Elisabeth L; Kooijman, Ron

    2004-11-15

    We previously reported that prolactin gene expression in the T-leukemic cell line Jurkat is stimulated by PGE(2) and that cAMP acts synergistically with Ca(2+) or protein kinase C on the activation of the upstream prolactin promoter. Using the transcription inhibitor actinomycin D, we now show that PGE(2)-induced prolactin expression requires de novo prolactin mRNA synthesis and that PGE(2) does not influence prolactin mRNA stability. Furthermore, PGE(2)-induced prolactin expression was inhibited by protein kinase inhibitor fragment 14-22 and BAPTA-AM, which respectively, inhibit protein kinase A- and Ca(2+)-mediated signaling cascades. Using specific PGE(2) receptor agonists and antagonists, we show that PGE(2) induces prolactin expression through engagement of E-prostanoid (EP) 3 and EP4 receptors. We also found that PGE(2) induces an increase in intracellular cAMP concentration as well as intracellular calcium concentration via EP4 and EP3 receptors, respectively. In transient transfections, 3000 bp flanking the leukocyte prolactin promoter conferred a weak induction of the luciferase reporter gene by PGE(2) and cAMP, whereas cAMP in synergy with ionomycin strongly activated the promoter. Mutation of a C/EBP responsive element at -214 partially abolished the response of the leukocyte prolactin promoter to PGE(2), cAMP, and ionomycin plus cAMP.

  10. Effect of fish oil on lateral mobility of prostaglandin F2α (FP) receptors and spatial distribution of lipid microdomains in bovine luteal cell plasma membrane in vitro.

    Science.gov (United States)

    Plewes, M R; Burns, P D; Graham, P E; Hyslop, R M; Barisas, B G

    2017-01-01

    Lipid microdomains are ordered regions on the plasma membrane of cells, rich in cholesterol and sphingolipids, ranging in size from 10 to 200 nm in diameter. These lipid-ordered domains may serve as platforms to facilitate colocalization of intracellular signaling proteins during agonist-induced signal transduction. It is hypothesized that fish oil will disrupt the lipid microdomains, increasing spatial distribution of these lipid-ordered domains and lateral mobility of the prostaglandin (PG) F2α (FP) receptors in bovine luteal cells. The objectives of this study were to examine the effects of fish oil on (1) the spatial distribution of lipid microdomains, (2) lateral mobility of FP receptors, and (3) lateral mobility of FP receptors in the presence of PGF2α on the plasma membrane of bovine luteal cells in vitro. Bovine ovaries were obtained from a local abattoir and corpora lutea were digested using collagenase. In experiment 1, lipid microdomains were labeled using cholera toxin subunit B Alexa Fluor 555. Domains were detected as distinct patches on the plasma membrane of mixed luteal cells. Fish oil treatment decreased fluorescent intensity in a dose-dependent manner (P oil treatment on lateral mobility of FP receptors. Fish oil treatment increased microdiffusion and macrodiffusion coefficients of FP receptors as compared to control cells (P oil-treated cells (P oil treatment. Lateral mobility of receptors was decreased within 5 min following the addition of ligand for control cells (P oil-treated cells (P > 0.10). The data presented provide strong evidence that fish oil causes a disruption in lipid microdomains and affects lateral mobility of FP receptors in the absence and presence of PGF2α.

  11. Fp+uFp+vFp+uvFp上的线性码%Linear Codes Over Fp+uFp+vFp+uvFp

    Institute of Scientific and Technical Information of China (English)

    许小芳

    2013-01-01

    The linear codes over the ring R=Fp+uFp+vFp+uυFp are discussed,where the ring R is not a finite chain ring.The structure of the ring R is analyzed and linear codes over this ring are defined,and the linear code of type (p4)k1 (p3)k2 (u)k3 (v)k4 (u+υ)k5 (p)k6 is characterized.%讨论了有限非链环R=Fp+uFpFp+uυFp上的线性码,分析了环R的结构,给出了此环上线性码的定义,并讨论了环R上(p4)k1 (p3)k2 (u)b(u)k4(u+υ)k5(p)k6型的线性码.

  12. Prostaglandin E2 upregulates β1 integrin expression via the E prostanoid 1 receptor/nuclear factor κ-light-chain-enhancer of activated B cells pathway in non-small-cell lung cancer cells.

    Science.gov (United States)

    Bai, Xiaoming; Yang, Qinyi; Shu, Wei; Wang, Jie; Zhang, Li; Ma, Juan; Xia, Shukai; Zhang, Min; Cheng, Shanyu; Wang, Yipin; Leng, Jing

    2014-05-01

    The prostaglandin E2 (PGE2) E prostanoid (EP)1 receptor shown to be associated with lung cancer cell invasion. However, the mechanism of EP1 receptor-mediated cell migration remains to be elucidated. β1 integrin is an essential regulator of the tumorigenic properties of non-small-cell lung carcinoma (NSCLC) cells. To date, little is known regarding the association between the EP1 receptor and β1 integrin expression. The present study investigated the effect of EP1 receptor activation on β1 integrin expression and cell migration in NSCLC cells. A total of 34 patients with clinical diagnosis of NSCLC and 10 patients with benign disease were recruited for the present study. The expression levels of the EP1 receptor and β1 integrin expression were studied in resected lung tissue using immunohistochemistry. A statistical analysis was performed using Stata se12.0 software. The effects of PGE2, EP1 agonist 17-phenyl trinor-PGE2 (17-PT-PGE2) and the nuclear factor κ-B (NF-κB) inhibitor on β1 integrin expression were investigated on A549 cells. The expression of β1 integrin and the phosphorylation of NF-κB‑p65 Ser536 was investigated by western blot analysis. Cell migration was assessed by a transwell assay. The results demonstrated that β1 integrin and EP1 receptor expression exhibited a positive correlation of evident significance in the 44 samples. The in vitro migration assay revealed that cell migration was increased by 30% when the cells were treated with 5 µM 17-PT-PGE2 and that the pre-treatment of β1 integrin monoclonal antibody inhibited 17-PT-PGE2‑mediated cell migration completely. PGE2 and 17-PT-PGE2 treatment increased β1 integrin expression. RNA interference against the EP1 receptor blocked the PGE2-mediated β1 integrin expression in A549 cells. Treatment with 17-PT-PGE2 induced NF-κB activation, and the selective NF-κB inhibitor pyrrolidinedithiocarbamate inhibited 17-PT-PGE2-mediated β1 integrin expression. In conclusion, the present

  13. Differences in the involvement of prostanoids from Kupffer cells in the mediation of anaphylatoxin C5a-, zymosan-, and lipopolysaccharide-dependent hepatic glucose output and flow reduction.

    Science.gov (United States)

    Pestel, Sabine; Schlaf, Gerald; Götze, Otto; Jungermann, Kurt; Schieferdecker, Henrike L

    2003-12-01

    Various inflammatory stimuli such as anaphylatoxin C5a, zymosan, and lipopolysaccharides (LPSs) have been reported both to enhance glucose output in the perfused rat liver and to induce prostanoid (ie, prostaglandin and thromboxane) release from Kupffer cells, the resident liver macrophages. Because prostanoids can enhance glucose output from hepatocytes, it was the aim of this study to compare the possible roles of prostanoids released after C5a, zymosan, and LPS in the mediation of hepatic glucose output. In perfused livers both C5a and zymosan immediately enhanced glucose output, reduced flow, and induced prostanoid overflow into the hepatic vein, but with different quantities and kinetics. Only the C5a-induced but not the zymosan-induced effects were abrogated by inhibitors of prostanoid signaling as the prostanoid synthesis inhibitor indomethacin and the thromboxane receptor antagonist daltroban. In contrast to C5a and zymosan, LPS had no effect on glucose output, flow rate, or prostanoid overflow. In isolated Kupffer cells, C5a and zymosan induced maximal release of prostaglandins D(2) and E(2) and of thromboxane A(2) within a period of 0 to 2 minutes and 5 to 15 minutes, respectively. In pulse-chase experiments, maximal prostanoid release was already observed after 2 minutes of continuous stimulation with C5a, but only after 10 to 15 minutes of continuous stimulation with zymosan. LPS-dependent prostanoid release was not seen before 1 hour. Thus, even though C5a, zymosan, and LPS induced prostanoid release from Kupffer cells, only C5a quickly regulated hepatic glucose metabolism in a prostanoid-dependent manner (due to the kinetics and quantities of prostanoids released).

  14. The pharmacological effect of BGC20-1531, a novel prostanoid EP4 receptor antagonist, in the prostaglandin E2 human model of headache

    DEFF Research Database (Denmark)

    Antonova, Maria; Wienecke, Troels; Maubach, Karen;

    2011-01-01

    Using a human Prostaglandin E(2) (PGE(2)) model of headache, we examined whether a novel potent and selective EP(4) receptor antagonist, BGC20-1531, may prevent headache and dilatation of the middle cerebral (MCA) and superficial temporal artery (STA). In a three-way cross-over trial, eight healt...

  15. Prostanoid-mediated contractions of the carotid artery become Nox2-independent with aging.

    Science.gov (United States)

    Meyer, Matthias R; Fredette, Natalie C; Barton, Matthias; Prossnitz, Eric R

    2015-08-01

    Aging is a major risk factor for carotid artery disease that may lead to stroke and dementia. Vascular effects associated with aging include increased vasomotor tone, as well as enhanced contractility to endothelial vasoconstrictor prostanoids and reduced nitric oxide (NO) bioactivity partly due to increased oxidative stress. We hypothesized that vascular NADPH oxidase (Nox)-derived superoxide may be involved in prostanoid- and NO-related functional aging. NO-mediated relaxations and prostanoid-mediated contractions to acetylcholine as well as phenylephrine-dependent contractions were investigated in the carotid artery from young (4 months) and aged mice (24 months). Gene expression of Nox subunits and endothelial NO synthase (eNOS) was determined in the carotid artery and aorta. In young mice, the thromboxane-prostanoid receptor antagonist SQ 29,548 fully blocked acetylcholine-induced contractions while reducing responses to phenylephrine by 75 %. The Nox2-targeted inhibitor Nox2ds-tat and the superoxide scavenger tempol reduced acetylcholine-stimulated, prostanoid-mediated contractions by 85 and 75 %, respectively, and phenylephrine-dependent contractions by 45 %. Unexpectedly, in aged mice, the substantial Nox2-dependent component of acetylcholine- and phenylephrine-induced, prostanoid-mediated contractions was abolished. In addition, endothelium-dependent, NO-mediated relaxations were impaired with aging. The expression of Nox subunits was greater in the aorta compared with the carotid artery, in which Nox1 was undetectable. eNOS gene expression was reduced in the aorta of aged compared to young mice. In conclusion, aging decreases prostanoid-mediated contractility in the carotid artery involving a loss of Nox2 activity and is associated with impaired endothelium-dependent, NO-mediated relaxation. These findings may contribute to a better understanding of the pathophysiology of carotid artery disease and the aging process.

  16. The pharmacological effect of BGC20-1531, a novel prostanoid EP4 receptor antagonist, in the prostaglandin E2 human model of headache

    DEFF Research Database (Denmark)

    Antonova, Maria; Wienecke, Troels; Maubach, Karen

    2011-01-01

    Using a human Prostaglandin E(2) (PGE(2)) model of headache, we examined whether a novel potent and selective EP(4) receptor antagonist, BGC20-1531, may prevent headache and dilatation of the middle cerebral (MCA) and superficial temporal artery (STA). In a three-way cross-over trial, eight healthy...... of the MCA or the STA (P > 0.05) with either dose of BGC20-1531 relative to placebo, although putative therapeutic exposures were not reached in all volunteers. In conclusion, these data suggest that the other EP receptors may be involved in PGE(2) induced headache and dilatation in normal subjects....... volunteers were randomly allocated to receive 200 and 400 mg BGC20-1531 and placebo, followed by a 25-min infusion of PGE(2). We recorded headache intensity on a verbal rating scale, MCA blood flow velocity and STA diameter. There was no difference in headache response or prevention of the dilation...

  17. Characteristics of sleep-wake cycles in mice lacking prostanoid DP receptors%前列腺素DP受体缺乏小鼠的睡眠-觉醒特征

    Institute of Scientific and Technical Information of China (English)

    马张庆; 洪宗元

    2006-01-01

    目的:探讨前列腺素DP受体(DPR)对小鼠睡眠-觉醒调节的影响.方法:在苯巴比妥麻醉下,于DPR基因敲除(KO)小鼠及其野生型(WT)小鼠大脑皮层及颈部肌肉分别植入脑电(Electroencephalogram, EEG)和肌电(Electromyogram, EMG)电极,用EEG/EMG睡眠记录系统于2000时开始连续记录24小时两种小鼠的脑电和肌电波,并用SLEEPSIGN软件进行分析.结果:两种小鼠表现出相同的睡眠-觉醒节律,且明时(800-2000)及暗时(2000-800)时相内两种小鼠的非快动眼(NREM) 睡眠和快动眼(REM)睡眠总量无差异.但与WT 小鼠相比,DPR-KO小鼠明时内的觉醒频率显著增高,NREM睡眠的平均时程显著缩短;且DPR-KO小鼠睡眠呈现低活性的θ波和高活性的δ波.结论:DPR在介导前列腺素D2诱导的睡眠中起着关键性调节作用,缺乏DPR将导致小鼠呈现低强度片段化的NREM睡眠和高警戒状态的REM睡眠.%AIM: To investigate the effect of prostanoid DP receptors (DPR) on sleep-wake regulation in mice. METHODS: Under pentobarbital anesthesia, mice were chronically implanted with electroencephalogram (EEG) and electromyogram (EMG) electrodes for polysomnographic recordings. The spontaneous sleep-wake cycles were monitored continuously by EEG/EMG recording system for 24 h beginning at 800 p.m. and analyzed by SLEEPSIGN software in DPR knock out (KO) and wild type (WT) mice. RESULTS: DPR-KO mice exhibited a similar circadian rhythm of sleep-wake cycles to WT mice. The amounts of rapid eye movement (REM) sleep or non-REM (NREM) sleep during both the light and dark periods were identical between the DPR-KO and WT mice. Whereas, an increase in the episode number of wakefulness and a shortage in the duration of NREM sleep were found in DPR-KO mice during the light period compared with WT mice. Moreover, DPR-KO mice showed lower activity in delta-wave component in NREM sleep and higher activity in theta-wave component in REM sleep than WT mice. CONCLUSION

  18. Diagnostic value of asymmetric striatal D2 receptor upregulation in Parkinson's disease: an [123I]IBZM and [123I]FP-CIT SPECT study.

    NARCIS (Netherlands)

    Verstappen, C.C.P.; Bloem, B.R.; Haaxma, C.A.; Oyen, W.J.G.; Horstink, M.W.I.M.

    2007-01-01

    INTRODUCTION: Striatal postsynaptic D2 receptors in Parkinson's disease (PD) are thought to be upregulated in the first years of the disease, especially contralateral to the clinically most affected side. The aim of this study was to evaluate whether the highest striatal D2 binding is found

  19. Imbalance of endogenous prostanoids in moderate-to-severe asthma

    Directory of Open Access Journals (Sweden)

    Masaya Takemura

    2017-01-01

    Conclusions: An imbalance in production, breakdown, or both between prostaglandin E2 and other prostanoids possibly due to epithelial damage may be involved in the pathogenesis of moderate-to-severe asthma.

  20. Prostanoids modulate inflammation and alloimmune responses during graft rejection

    Directory of Open Access Journals (Sweden)

    P.N. Rocha

    2005-12-01

    Full Text Available Acute rejection of a transplanted organ is characterized by intense inflammation within the graft. Yet, for many years transplant researchers have overlooked the role of classic mediators of inflammation such as prostaglandins and thromboxane (prostanoids in alloimmune responses. It has been demonstrated that local production of prostanoids within the allograft is increased during an episode of acute rejection and that these molecules are able to interfere with graft function by modulating vascular tone, capillary permeability, and platelet aggregation. Experimental data also suggest that prostanoids may participate in alloimmune responses by directly modulating T lymphocyte and antigen-presenting cell function. In the present paper, we provide a brief overview of the alloimmune response, of prostanoid biology, and discuss the available evidence for the role of prostaglandin E2 and thromboxane A2 in graft rejection.

  1. 前列腺素E2受体亚型EP2和EP4的最新研究进展%The Latest Progress in E-Prostanoid (EP) Receptor Subtypes EP2 and EP4

    Institute of Scientific and Technical Information of China (English)

    朱森; 杨吉春; 管又飞

    2009-01-01

    Prostaglandin(PG)E2 exerts its physiological actions via four functionally antagonistic E-prostanoid (EP) receptors, which are designated as subtypes EP1, EP2, EP3 and EP4 respectively. The subtype EP3 has multiple mRNA splicing isoforms. All of these receptors are G-protein coupled receptors (GPCRs). The EP receptor subtypes exhibit different tissue distribution and expressional regulation, and mediate various signaling pathway and physiological functions. Among the 4 EP receptors, EP2 and EP4 are coupled to the same Goprotein (stimulate G-protein, Gs), and increase cellular cAMP level upon activation. EP2 and EP4 function redundantly in some physiological processes, while they play distinct roles in some other processes. In the current paper, the latest advances in study of EP2 and EP4 receptors will be summarized and discussed.%前列腺素E2(PGE2)通过作用于4种功能相互拮抗的受体广泛地参与了机体及细胞代谢过程.这4种PGE2受体分别被命名为EP1、EP2、EP3和E4,其中EP3又因mRNA的不同剪切方式分为多种亚型.所有的这些PGE2受体均是G-蛋白偶联受体,但具有不同的组织定位和表达调控方式,并介导不同的信号传导通路和生理学作用.在这4种受体中,EP2和EP4与同一种类型的G蛋白(激活型G蛋白,Gs)偶联,激活后都能增加细胞内的cAMP,因此它们的功能具有一定的重叠性,但在某些生理过程中它们又发挥着截然不同的作用.本文将就这两型受体及其生理学功能进行分析和总结,并重点讨论有关其研究的最新进展.

  2. FP-soft Boolean Algebra%FP-软布尔代数

    Institute of Scientific and Technical Information of China (English)

    刘卫锋; 许宏伟; 何霞

    2015-01-01

    FP-软集(Fuzzy Parameterized Soft Sets)与布尔代数相结合,定义了FP-软布尔代数、FP-软布尔子代数、FP-软布尔代数的FP-软理想、FP-理想软布尔代数等概念,研究了它们的相关性质.最后,讨论了FP-软布尔代数的同态.

  3. Computer Security: Well fought, FP!

    CERN Multimedia

    Stefan Lueders, Computer Security Team

    2015-01-01

    We are used to spam and phishing emails. But at the end of last year, a very special email struck one of our colleagues in the FP Department.   An accountant was gently asked in an email from “Rolf.Heuer@cern.ch” to prepare a financial transaction - in the strictest confidence. A phone call from the beneficiary to the accountant was made in an attempt to support this request. Despite being instructed not to talk to anyone, the e-mail, the phone conversation and the circumstances were all so suspicious that our colleague consulted his hierarchy, the internal audit service and us. Well done, FP Department! This is a rare case of an attempt at “social engineering”, i.e. luring someone into doing something detrimental to the Organization. The e-mail was fake. While it appeared to come from “Rolf.Heuer@cern.ch”, it actually came from an alleged fraudster outside CERN. The e-mail and the phone call showed that he was well prepared and dire...

  4. Anti-Inflammatory Prostanoids: Focus on the Interactions between Electrophile Signaling and Resolution of Inflammation

    Directory of Open Access Journals (Sweden)

    Beatriz Díez-Dacal

    2010-01-01

    Full Text Available Prostanoids are products of cyclooxygenase biosynthetic pathways and constitute a family of lipidic mediators of widely diverse structures and biological actions. Besides their known proinflammatory role, numerous works have revealed the anti-inflammatory effects of various prostanoids and established their role in the resolution of inflammation. Among these, prostaglandins with cyclopentenone structure (cyPG are electrophilic lipids that may act through various mechanisms, including the activation of nuclear and membrane receptors and, importantly, direct addition to protein cysteine residues and modification of protein function. Due to their ability to influence cysteine modification–mediated signaling, cyPG may play a critical role in the interplay between redox and inflammatory signaling pathways. Moreover, cellular redox status modulates cyPG addition to proteins; thus, a reciprocal regulation exists between these two factors. After initial controversy, it is becoming clear that endogenous cyPG are generated at concentrations sufficient to promote inflammatory resolution. As for other prostanoids, cyPG effects are highly dependent on context factors and they may exert pro- or anti-inflammatory actions in a cell type–dependent manner, or even biphasic or dual actions in a given cell type or tissue. In light of the growing number of cyPG protein targets identified, cyPG resemble other pleiotropic mediators acting through protein modification. However, their complex structure results in an inter- and intramolecular selectivity of the residues being modified, thus opening the way for structure-activity and drug discovery studies. Detailed characterization of cyPG interactions with cellular proteins will help us to understand their mechanism of action fully and establish their therapeutic potential in inflammation.

  5. The effects of calcineurin inhibitors on prostanoid synthesis

    DEFF Research Database (Denmark)

    Øzbay, Aygen; Stubbe, Jane; Jespersen, Bente

    2013-01-01

    The calcineurin inhibitors (CNIs) cyclosporine (CsA) and tacrolimus (Tac) are implicated in post-transplant complications such as cardiovascular morbidity. Prostanoids are fatty acid-derived compounds essential for controlling cardiovascular homeostasis. We tested the hypothesis that CNIs suppress...

  6. Mechanisms Underlying Enhanced Noradrenaline-Induced Femoral Arterial Contractions of Spontaneously Hypertensive Rats: Involvement of Endothelium-Derived Factors and Cyclooxygenase-Derived Prostanoids.

    Science.gov (United States)

    Matsumoto, Takayuki; Watanabe, Shun; Iguchi, Maika; Ando, Makoto; Oda, Mirai; Nagata, Mako; Yamada, Kosuke; Taguchi, Kumiko; Kobayashi, Tsuneo

    2016-01-01

    We investigated the relationship between noradrenaline (NAd)-induced contractions, endothelial function, and hypertension in femoral arteries isolated from spontaneously hypertensive rats (SHR). In the femoral arteries of SHR, vs. age-matched control Wistar Kyoto (WKY) rats, contractions induced by NAd were increased. These effects were enhanced by endothelial denudation, which abolished the differences between the two groups. NAd-induced contractions were enhanced by nitric oxide (NO) synthase inhibition, and further increased by the blockade of endothelium-derived hyperpolarizing factor (EDHF). Conversely, NAd-induced contractions were inhibited by cyclooxygenase (COX) inhibition. In addition, in SHR arteries, acetylcholine-induced relaxation was reduced, and components of endothelium-derived factors were altered, such as increased COX-derived vasoconstrictor prostanoids, reduced EDHF, and preserved NO-mediated relaxation. In the femoral arteries of SHR, the production of prostanoids [6-keto prostaglandin (PG)F1α (a metabolite of prostacyclin (PGI2), PGE2, and PGF2α] and COX-2 protein were increased compared with that in WKY rats. By contrast, contractions induced by beraprost (a stable PGI2 analogue), PGE2, and U46619 (thromboxane/prostanoid receptor agonist) were similar between the SHR and WKY groups. Thus, NAd-induced femoral arterial contractions are augmented in SHR resulting from endothelial dysfunction and increased COX-derived vasoconstrictor prostanoid levels.

  7. Blockade of nonhormonal fibroblast growth factors by FP-1039 inhibits growth of multiple types of cancer.

    Science.gov (United States)

    Harding, Thomas C; Long, Li; Palencia, Servando; Zhang, Hongbing; Sadra, Ali; Hestir, Kevin; Patil, Namrata; Levin, Anita; Hsu, Amy W; Charych, Deborah; Brennan, Thomas; Zanghi, James; Halenbeck, Robert; Marshall, Shannon A; Qin, Minmin; Doberstein, Stephen K; Hollenbaugh, Diane; Kavanaugh, W Michael; Williams, Lewis T; Baker, Kevin P

    2013-03-27

    The fibroblast growth factor (FGF) pathway promotes tumor growth and angiogenesis in many solid tumors. Although there has long been interest in FGF pathway inhibitors, development has been complicated: An effective FGF inhibitor must block the activity of multiple mitogenic FGF ligands but must spare the metabolic hormone FGFs (FGF-19, FGF-21, and FGF-23) to avoid unacceptable toxicity. To achieve these design requirements, we engineered a soluble FGF receptor 1 Fc fusion protein, FP-1039. FP-1039 binds tightly to all of the mitogenic FGF ligands, inhibits FGF-stimulated cell proliferation in vitro, blocks FGF- and vascular endothelial growth factor (VEGF)-induced angiogenesis in vivo, and inhibits in vivo growth of a broad range of tumor types. FP-1039 antitumor response is positively correlated with RNA levels of FGF2, FGF18, FGFR1c, FGFR3c, and ETV4; models with genetic aberrations in the FGF pathway, including FGFR1-amplified lung cancer and FGFR2-mutated endometrial cancer, are particularly sensitive to FP-1039-mediated tumor inhibition. FP-1039 does not appreciably bind the hormonal FGFs, because these ligands require a cell surface co-receptor, klotho or β-klotho, for high-affinity binding and signaling. Serum calcium and phosphate levels, which are regulated by FGF-23, are not altered by administration of FP-1039. By selectively blocking nonhormonal FGFs, FP-1039 treatment confers antitumor efficacy without the toxicities associated with other FGF pathway inhibitors.

  8. Prostanoid Receptor EP2 as a Therapeutic Target

    OpenAIRE

    Ganesh, Thota

    2013-01-01

    Cycoloxygenase-2 (COX-2) induction is prevalent in a variety of (brain and peripheral) injury models where COX-2 levels correlate with disease progression. Thus, COX-2 has been widely explored for anti-inflammatory therapy with COX-2 inhibitors, which proved to be effective in reducing the pain and inflammation in patients with arthritis and menstrual cramps, but they have not provided any benefit to patients with chronic inflammatory neurodegenerative disease. Recently, two COX-2 drugs: rofe...

  9. Purinergic signaling induces cyclooxygenase-1-dependent prostanoid synthesis in microglia: roles in the outcome of excitotoxic brain injury.

    Directory of Open Access Journals (Sweden)

    Josef Anrather

    Full Text Available Cyclooxygenases (COX are prostanoid synthesizing enzymes constitutively expressed in the brain that contribute to excitotoxic neuronal cell death. While the neurotoxic role of COX-2 is well established and has been linked to prostaglandin E(2 synthesis, the role of COX-1 is not clearly understood. In a model of N-Methyl-D-aspartic acid (NMDA induced excitotoxicity in the mouse cerebral cortex we found a distinctive temporal profile of COX-1 and COX-2 activation where COX-1, located in microglia, is responsible for the early phase of prostaglandin E(2 synthesis (10 minutes after NMDA, while both COX-1 and COX-2 contribute to the second phase (3-24 hours after NMDA. Microglial COX-1 is strongly activated by ATP but not excitatory neurotransmitters or the Toll-like receptor 4 ligand bacterial lipopolysaccharide. ATP induced microglial COX-1 dependent prostaglandin E(2 synthesis is dependent on P2X7 receptors, extracellular Ca(2+ and cytoplasmic phospholipase A2. NMDA receptor activation induces ATP release from cultured neurons leading to microglial P2X7 receptor activation and COX-1 dependent prostaglandin E(2 synthesis in mixed microglial-neuronal cultures. Pharmacological inhibition of COX-1 has no effect on the cortical lesion produced by NMDA, but counteracts the neuroprotection exerted by inhibition of COX-2 or observed in mice lacking the prostaglandin E(2 receptor type 1. Similarly, the neuroprotection exerted by the prostaglandin E(2 receptor type 2 agonist butaprost is not observed after COX-1 inhibition. P2X7 receptors contribute to NMDA induced prostaglandin E(2 production in vivo and blockage of P2X7 receptors reverses the neuroprotection offered by COX-2 inhibition. These findings suggest that purinergic signaling in microglia triggered by neuronal ATP modulates excitotoxic cortical lesion by regulating COX-1 dependent prostanoid production and unveil a previously unrecognized protective role of microglial COX-1 in excitotoxic brain

  10. Prostanoids counterbalance the synergism between endothelin-1 and angiotensin II in mesenteric veins of trained rats.

    Science.gov (United States)

    Chies, Agnaldo Bruno; de Oliveira, Priscilla Bianca; Rossignoli, Patrícia de Souza; Baptista, Rafaela de Fátima Ferreira; de Lábio, Roger William; Payão, Spencer Luiz Marques

    2017-02-01

    Exercise-induced adaptations of the modulating mechanisms that influence the angiotensin (Ang II) responses assume different features depending on the venous bed. In femoral veins, exercise mobilizes vasodilator prostanoids to cooperate with NO in order to maintain reduced Ang II responses. On the other hand, exercise's influence on the Ang II responses in veins that drain blood from the mesenteric region has been poorly described. Therefore, the present study aimed to identify the effects of a single bout of exercise, as well as exercise training, on the Ang II responses in mesenteric veins. The present study also aimed to investigate the involvement of prostanoids, NO and ET-1 in eventual exercise-induced modifications in these veins. To this end, mesenteric veins taken from resting-sedentary, exercised-sedentary, resting-trained and exercised-trained animals were studied in organ baths. In addition, the mRNA expression of prepro-endothelin-1 (ppET-1), as well as that of the ETA and ETB receptors, were quantified by real-time PCR in these veins. The results show that, either in absence or in presence of L-NAME, the Ang II responses were not different between groups. In the presence of indomethacin, higher Ang II responses were observed in the resting-trained animals than in the resting-sedentary animals. This difference, however, disappeared when L-NAME, BQ-123 or BQ-788 were added during incubation. In addition, no differences in ppET-1, ETA or ETB mRNA expression were observed between groups. Furthermore, in the presence of PD123,319, the Ang II responses in the exercised-sedentary animals were higher than those in the resting-sedentary animals. In conclusion, exercise training mobilizes endothelin-1 (ET-1) to reinforce the Ang II-induced responses mainly through ETA activation. On the other hand, vasodilator prostanoids are mobilized to act in parallel with NO in order to counterbalance the Ang II responses that have been potentiated by ET-1 in these trained

  11. Bibliometric performance analysis of publications from Danish researchers linked to FP6 and FP7

    DEFF Research Database (Denmark)

    Schneider, Jesper Wiborg; Ryan, Thomas Kjeldager

    2015-01-01

    This chapter presents an analysis29 of the impact of Danish scientific publications that were the result of FP6 or FP7 funding. The purpose is to gain an insight into the scientific impact researchers can achieve when participating in FP6 and FP7. In order to look at impact we have identified...... citations belonging to scientific publications with at least one Danish author. This is done using data from the international citation database Web of Science (WoS). These results are compared to the results of the bibliometric analyses from the previous evaluations of the Danish National Research...

  12. Restoration of depressed prostanoid-induced ileal contraction in spontaneously hypertensive rats by dietary fish oil.

    Science.gov (United States)

    Patten, Glen S; Adams, Michael J; Dallimore, Julie A; Rogers, Paul F; Topping, David L; Abeywardena, Mahinda Y

    2005-01-01

    We have reported that dietary fish oil (FO) rich in n-3 PUFA modulates gut contractility. It was further demonstrated that the gut of spontaneously hypertensive rats (SHR) has a depressed contractility response to prostaglandins (PG) compared with normotensive Wistar-Kyoto (WKY) rats. We investigated whether feeding diets supplemented with n-3 PUFA increased gut contractility and restored the depressed prostanoid response in SHR gut. Thirteen-week-old SHR were fed diets containing fat at 5 g/100 g as coconut oil (CO), lard, canola oil containing 10% (w/w) n-3 FA as alpha-linolenic acid (1 8:3n-3), or FO (as HiDHA, 22:6n-3) for 12 wk. A control WKY group was fed 5 g/100 g CO in the diet. As confirmed, the SHR CO group had a significantly lower gut response to PGE2 and PGF2alpha compared with the WKY CO group. Feeding FO increased the maximal contraction response to acetylcholine in the ileum compared with all diets and in the colon compared with lard, and restored the depressed response to PGE2 and PGF2alpha in the ileum but not the colon of SHR. FO feeding also led to a significant increase in gut total phospholipid n-3 PUFA as DHA (22:6n-3) with lower n-6 PUFA as arachidonic acid (20:4n-6). Canola feeding led to a small increase in ileal EPA (20:5n-3) and DHA and in colonic DHA without affecting contractility. However, there was no change in ileal membrane muscarinic binding properties due to FO feeding. This report confirms that dietary FO increases muscarinic- and eicosanoid receptor-induced contractility in ileum and that the depressed prostanoid response in SHR ileum, but not colon, is restored by tissue incorporation of DHA as the active nutrient.

  13. NO and prostanoids blunt endothelin-mediated coronary vasoconstrictor influence in exercising swine

    NARCIS (Netherlands)

    D. Merkus (Daphne); O. Sorop (Oana); B. Houweling (Birgit); F. Boomsma (Frans); A.H. van den Meiracker (Anton); D.J.G.M. Duncker (Dirk)

    2006-01-01

    textabstractWithdrawal of the endothelin (ET)-mediated vasoconstrictor influence contributes to metabolic coronary vasodilation during exercise. Because production of nitric oxide (NO) and prostanoids increases with increasing shear stress and because NO and prostanoids are able to modify the

  14. Women's development key to MCH/FP.

    Science.gov (United States)

    1991-05-01

    The Sri Lankan government has included women in its development process thereby raising literacy levels to 91% for urban women and 87% for rural women. Their successful participation has in turn resulted in improvements in maternal and child health (MCH) and family planning (FP) acceptance. Indeed MCH/FP promotion could not have occurred without their participation in development. Since the 1960s, the Health and Women's Affairs Ministry continues to provide broad support for grass roots health care, such as strengthening the capacity of local clinics to increase coverage of health monitoring for women and children. There fore infant mortality in Sri Lanka has decreased from 47.5 in 1970 to 34 in 1980 to 19 in 1989. In addition, the total fertility rate fell from 5 in 1962-1964 to 3.4 in 1980-1982 to 2.8 in 1982-1987. The Ministry initiated its Integrated FP, Nutrition, and Parasite Control Project (IP) in 8 pilot areas in 1981. IP continues to encourage women's developed and MCH/FP at the grass roots level. In fact, FP acceptance rates increased from 31.8% in 1980 to 59% in 1989 in Nakulugamuwa and from 2.3% in 1980 to 70.5% in 1989 in Galnewa. The MCH component operating from community level clinics includes growth monitoring and immunization. Project activities include construction of latrines and wells, promotion of regular health examinations for mothers and children, FP education, counseling, nutrition promotion for children, and training programs for health staff, community volunteers, mothers' groups, and teachers. The volunteers form a link between the community and government health workers. Mothers' groups participate in school nutrition programs, home gardening, and income generation. Parasite control is consequently accomplished by community health and environmental sanitation promotion.

  15. On FP-small Injectivity And J-injectivity%FP-small内射性与J-内射性

    Institute of Scientific and Technical Information of China (English)

    向跃明; 王树桂

    2013-01-01

    作为FP-内射性的推广,在文中引入了FP-small内射性.研究了右FP-small内射环的一些性质.利用FP-small内射性给出了FP-环与QF-环的一些新刻画.同时,还研究了环模的J-内射性.构造了一些相关例子.

  16. Modulation of noradrenaline release in rat isolated stomach by prostanoids, but not by histaminergic mechanisms.

    Science.gov (United States)

    Racké, K; Berrino, L; Möhlig, A; Jäger, R; Griepenkerl, I; Bräutigam, M; Reimann, A

    1995-12-01

    Several gastric functions are modulated by the sympathetic nervous system, but local mechanisms involved in the control of noradrenaline release are largely unknown. Overflow of endogenous noradrenaline was studied from isolated rat stomach incubated in Ussing chambers allowing the separate determination of mucosal and serosal overflow. Spontaneous noradrenaline overflow was similar at the mucosal and serosal side, but electrical field stimulation caused a frequency-dependent increase in noradrenaline overflow selectively at the serosal side. Evoked noradrenaline overflow was blocked by tetrodotoxin, not affected by indometacin and markedly enhanced (by about 250%) by yohimbine. In the presence of indometacin and yohimbine, sulprostone (an agonist at EP1/EP3 receptors) and misoprostol (an agonist at EP2/EP3 receptors) reduced the noradrenaline overflow evoked by stimulation at 3 Hz maximally by about 80% (EC50: 6 nmol/l and 11 nmol/l, respectively). The EP1 receptor selective antagonist AH 6809 (6-isopropoxy-9-oxoxanthene-2-carboxylic acid) did not antagonize the inhibition by sulprostone. Noradrenaline overflow evoked by stimulation at 1 Hz and 3 Hz was increased by scopolamine by about 50% and almost completely inhibited by oxotremorine. Neither, histamine nor the H3 receptor selective agonist (R)-alpha-methyl-histamine, nor the H1, H2 and H3 selective receptor antagonists mepyramine, cimetidine and thioperamide significantly affected noradrenaline overflow evoked by stimulation at 1 Hz or 3 Hz. In conclusion, impulse-induced noradrenaline release in the rat stomach is controlled by multiple presynaptic mechanisms involving alpha 2-adrenergic autoreceptors, EP3 prostanoid and muscarine heteroreceptors, whereas histaminergic mechanisms do not appear to be significant.

  17. Efficacy of bosentan in the treatment of Raynaud’s phenomenon in patients with systemic sclerosis never treated with prostanoids

    Directory of Open Access Journals (Sweden)

    S. Parisi

    2014-03-01

    Full Text Available The objective of this study was to evaluate the efficacy of the endothelin receptor antagonist, bosentan, in patients with Raynaud’s phenomenon secondary to systemic sclerosis never treated with prostanoids and without digital ulcers. The study design is a preliminary, prospective open label trial. The patients recruited took one 62.5 mg dose of bosentan twice daily for 4 weeks, followed by 125 mg twice daily for 24 weeks. Of the 10 patients recruited, all completed the study. The reduction in Raynaud’s phenomenon attacks at week 24 from the baseline was statistically significant (Δ-1.3, P=0.0126. The Raynaud’s condition score showed a statistically significant improvement (Δ-1.4, P=0.0279, as did the visual analog pain scale (Δ-1.5, P=0.0016 at the 24th week. Bosentan appears to be effective and may be a valid alternative for the treatment of severe secondary Raynaud’s phenomenon for patients where prostanoids therapy is contraindicated or refused.

  18. Efficacy of bosentan in the treatment of Raynaud's phenomenon in patients with systemic sclerosis never treated with prostanoids.

    Science.gov (United States)

    Parisi, S; Bruzzone, M; Centanaro Di Vittorio, C; Laganà, A; Peroni, C L; Fusaro, E

    2014-03-17

    The objective of this study was to evaluate the efficacy of the endothelin receptor antagonist, bosentan, in patients with Raynaud's phenomenon secondary to systemic sclerosis never treated with prostanoids and without digital ulcers. The study design is a preliminary, prospective open label trial. The patients recruited took one 62.5 mg dose of bosentan twice daily for 4 weeks, followed by 125 mg twice daily for 24 weeks. Of the 10 patients recruited, all completed the study. The reduction in Raynaud's phenomenon attacks at week 24 from the baseline was statistically significant (Δ-1.3, P=0.0126). The Raynaud's condition score showed a statistically significant improvement (Δ-1.4, P=0.0279), as did the visual analog pain scale (Δ-1.5, P=0.0016) at the 24th week. Bosentan appears to be effective and may be a valid alternative for the treatment of severe secondary Raynaud's phenomenon for patients where prostanoids therapy is contraindicated or refused.

  19. Elevated mRNA expression of PGF2alpha receptor splice variant 2(FP-V2) in human decidua is associated with incomplete mifepristone-misoprostol-induced early medical abortion by regulation of interleukin-8.

    NARCIS (Netherlands)

    Ma, C.; Feng, W.; Han, W.; Lu, Y.; Liu, W.; Sui, Y.; Zhao, N.; Lye, S.J.; Li, J.

    2016-01-01

    OBJECTIVE: The combination of mifepristone and misoprostol is an established method for the induction of early abortion, but 15% of women still experience the unpleasant side effect of incomplete medical abortion. The purpose of this study was to determine whether prostaglandin (PG) F2alpha receptor

  20. JENDL FP decay data file 2000

    Energy Technology Data Exchange (ETDEWEB)

    Katakura, Jun-ichi [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment; Yoshida, Tadashi [Musashi Inst. of Tech., Tokyo (Japan); Oyamatsu, Kazuhiro [Aichi Shukutoku Univ., Nagakute, Aichi (Japan); Tachibana, Takahiro [Waseda Univ., Tokyo (Japan)

    2001-07-01

    A decay data file of fission product (FP) nuclides has been developed for the use in nuclear technology field as one of special purpose files of JENDL (Japanese Evaluated Nuclear Data Library) in the format of ENDF/B and it is called JENDL FP Decay Data File 2000. The file includes the decay data for 1229 fission product nuclides: 142 stable and 1087 unstable nuclides. The data included for a nuclide are decay modes, their Q values and branching ratios, average decay energy values of beta-rays, gamma-rays and alpha-particles and their spectral data. The primary source of the decay data is ENSDF (Evaluated Nuclear Structure Data File), which is the internationally recognized data file of nuclear structure properties. The data in ENSDF, however, cover only measured ones. The data of the short-lived nuclides needed for the application fields such as decay heat prediction are often incomplete or not measured because of their short half-lives. For such nuclides a theoretical model calculation is applied to derive the needed data such as average decay energies and spectral data. The data in JENDL FP Decay Data File 2000 have been tested by summation calculation comparing its results with measured data of decay heat values and aggregate fission product spectra of various fissioning nuclei. The comparison showed good agreement between the calculated results and the measured values. (author)

  1. FUNCTIONAL CORRELATION OF FP AND DC METHODS

    Directory of Open Access Journals (Sweden)

    Marin Kaluža

    2013-02-01

    Full Text Available Most of organizations today use information-communication technologies (ICT for building an information system (IS. IS is assembled of hardware, software, network resources, organizational and human resources. In IS development process, complexity is crucial for evaluating quantities of resources needed (time, people, money, equipment. Complexity of an IS can be evaluated and/or measured in different phases of development. There are many methods for measuring complexity, but mostly used and thoroughly described method is Function Point Analysis (FP. The opposite method, Database Complexity (DC, does not measure all the aspects of IS, but it could evaluate system complexity depending on the database complexity. DC method is intended to be used for measuring semantic complexity of the IS database, and can be shown by counting attributes A and foreign keys F. This paper describes a very high correlation between FP and DC methods, and defines a function which can in 95% of accuracy express FP values from measured DC values.

  2. A hybrid Michelson-FP interference fiber sensor

    Science.gov (United States)

    Liu, Zhihai; Zhang, Yaxun; Wang, Zhenzhen; Zhang, Yu; Zhao, Enming; Zhou, Ai; Yuan, Libo

    2015-09-01

    A novel hybrid Michelson-FP (M-FP) interference fiber sensor based on a twin-core fiber has been proposed. It consists of an in-fiber integrated Michelson interferometer and an air FP cavities. The radial strain and axial strain sensing properties are explored and analyzed. By using this novel structure, we can measure radial strain and axial strain simultaneously.

  3. An algorithm for DLP on anomalous elliptic curves over Fp

    Institute of Scientific and Technical Information of China (English)

    祝跃飞; 裴定一

    2002-01-01

    This paper improves the method of discrete logarithm on anomalous elliptic curves, and establishes an isomorphism from E(Fp) to Fp which can be more easily implemented. Fruthermore, we give an optimized algorithm for discrete logarithm on anomalous elliptic curves E(Fp).

  4. Evaluation of pancreatic VMAT2 binding with active and inactive enantiomers of 18F-FP-DTBZ in baboons

    Science.gov (United States)

    Lim, Keunpoong; Labaree, David; Ropchan, Jim; Harris, Paul; Huang, Yiyun; Ichise, Masanori; Carson, Richard E.; Cline, Gary W.

    2017-01-01

    Introduction 18F-Fluoropropyl-(+)-dihydrotetrabenazine (18F-FP-(+)-DTBZ) is a vesicular monoamine transporter type 2 (VMAT2) radiotracer for positron emission tomography (PET) imaging to quantify human β-cell mass. Renal cortex and spleen have been suggested as reference regions, however, little is known about 18F-FP-(+)-DTBZ binding in these regions including the fraction of radiometabolite. We compared the kinetics of 18F-FP-(+)-DTBZ and its inactive enantiomer 18F-FP-(−)-DTBZ in baboons, estimated the non-displaceable binding (VND) of the tracers, and used ex vivo studies to measure radiometabolite fractions. Methods PET scans were conducted for up to 4 h with (+) and (−) enantiomers. Displacement experiments using unlabeled (+) and (−) enantiomers of FP-DTBZ and fluvoxamine (to evaluate sigma-1 receptor binding) were performed. SUV curves were used to calculate displacement values in the pancreas, renal cortex, and spleen. Distribution volumes (VT) were computed, and three approaches for calculation of VND were compared: (1) 18F-FP-(+)-DTBZ reference VT, (2) 18F-FP-(−)-DTBZ pancreatic VT, and (3) a scaled 18F-FP-(+)-DTBZ reference VT values. Ex vivo study was conducted to measure radiometabolite fraction in homogenized tissue samples from baboons at 90 min post-injection. Results Spleen uptake was lowest for both tracers. Highest uptake was in the pancreas with 18F-FP-(+)-DTBZ and renal cortex with 18F-FP-(−)-DTBZ. Substantial displacement effect was observed only with unlabeled FP-(+)-DTBZ in the 18F-FP-(+)-DTBZ studies. Radiometabolite fraction was higher in the renal cortex than the spleen. Approaches (1) and (3) with spleen to estimate VND provided lowest inter-subject variability of BPND. Conclusions VT differences among organs and between enantiomers indicated that scaling of reference region values is needed for quantification of VMAT2 binding in the pancreas with 18F-FP-(+)-DTBZ. Since the kidney PET signal has greater partial volume

  5. Hilbert-Huang Transformation Based Analyses of FP1, FP2, and Fz Electroencephalogram Signals in Alcoholism.

    Science.gov (United States)

    Lin, Chin-Feng; Su, Jiun-Yi; Wang, Hao-Min

    2015-09-01

    Chronic alcoholism may damage the central nervous system, causing imbalance in the excitation-inhibition homeostasis in the cortex, which may lead to hyper-arousal of the central nervous system, and impairments in cognitive function. In this paper, we use the Hilbert-Huang transformation (HHT) method to analyze the electroencephalogram (EEG) signals from control and alcoholic observers who watched two different pictures. We examined the intrinsic mode function (IMF) based energy distribution features of FP1, FP2, and Fz EEG signals in the time and frequency domains for alcoholics. The HHT-based characteristics of the IMFs, the instantaneous frequencies, and the time-frequency-energy distributions of the IMFs of the clinical FP1, FP2, and Fz EEG signals recorded from normal and alcoholic observers who watched two different pictures were analyzed. We observed that the number of peak amplitudes of the alcoholic subjects is larger than that of the control. In addition, the Pearson correlation coefficients of the IMFs, and the energy-IMF distributions of the clinical FP1, FP2, and Fz EEG signals recorded from normal and alcoholic observers were analyzed. The analysis results show that the energy ratios of IMF4, IMF5, and IMF7 waves of the normal observers to the refereed total energy were larger than 10 %, respectively. In addition, the energy ratios of IMF3, IMF4, and IMF5 waves of the alcoholic observers to the refereed total energy were larger than 10 %. The FP1 and FP2 waves of the normal observers, the FP1 and FP2 waves of the alcoholic observers, and the FP1 and Fz waves of the alcoholic observers demonstrated extremely high correlations. On the other hand, the FP1 waves of the normal and alcoholic observers, the FP1 wave of the normal observer and the FP2 wave of the alcoholic observer, the FP1 wave of the normal observer and the Fz wave of the alcoholic observer, the FP2 waves of the normal and alcoholic FP2 observers, and the FP2 wave of the normal observer and

  6. Web Classification Using DYN FP Algorithm

    Directory of Open Access Journals (Sweden)

    Bhanu Pratap Singh

    2014-01-01

    Full Text Available Web mining is the application of data mining techniques to extract knowledge from Web. Web mining has been explored to a vast degree and different techniques have been proposed for a variety of applications that includes Web Search, Classification and Personalization etc. The primary goal of the web site is to provide the relevant information to the users. Web mining technique is used to categorize users and pages by analyzing users behavior, the content of pages and order of URLs accessed. In this paper, proposes an auto-classification algorithm of web pages using data mining techniques. The problem of discovering association rules between terms in a set of web pages belonging to a category in a search engine database, and present an auto – classification algorithm for solving this problem that are fundamentally based on FP-growth algorithm

  7. Network Intrusion Detection Using FP Tree Rules

    Directory of Open Access Journals (Sweden)

    P Srinivasulu

    2009-07-01

    Full Text Available In the faceless world of the Internet, online fraud is one of the greatest reasons of loss for web merchants. Advanced solutions are needed to protect e-businesses from the constant problems of fraud. Many popular fraud detection algorithms require supervised training, which needs human intervention to prepare training cases. Since it is quite often for an online transaction database to have Terabyte-level storage, human investigation to identify fraudulent transactions is very costly. This paper describes the automatic design of user profiling method for the purpose of fraud detection. We use a FP (Frequent Pattern Tree rule-learning algorithm to adaptively profile legitimate customer behavior in a transaction database. Then the incoming transactions are compared against the user profile to uncover the anomalies. The anomaly outputs are used as input to an accumulation system for combining evidence to generate high-confidence fraud alert value. Favorable experimental results are presented.

  8. Network Intrusion Detection Using FP Tree Rules

    CERN Document Server

    Srinivasulu, P; Babu, I Ramesh

    2010-01-01

    In the faceless world of the Internet,online fraud is one of the greatest reasons of loss for web merchants.Advanced solutions are needed to protect e businesses from the constant problems of fraud.Many popular fraud detection algorithms require supervised training,which needs human intervention to prepare training cases.Since it is quite often for an online transaction database to ha e Terabyte level storage,human investigation to identify fraudulent transactions is very costly.This paper describes the automatic design of user profiling method for the purpose of fraud detection.We use a FP (Frequent Pattern) Tree rule learning algorithm to adaptively profile legitimate customer behavior in a transaction database.Then the incoming transactions are compared against the user profile to uncover the anomalies The anomaly outputs are used as input to an accumulation system for combining evidence to generate high confidence fraud alert value. Favorable experimental results are presented.

  9. Lazy evaluation of FP programs: A data-flow approach

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Y.H. [International Business Machines Corp., Yorktown Heights, NY (United States). Thomas J. Watson Research Center; Gaudiot, J.L. [University of Southern California, Los Angeles, CA (United States). Computer Research Inst.

    1988-12-31

    This paper presents a lazy evaluation system for the list-based functional language, Backus` FP in data-driven environment. A superset language of FP, called DFP (Demand-driven FP), is introduced. FP eager programs are transformed into DFP lazy programs which contain the notions of demands. The data-driven execution of DFP programs has the same effects of lazy evaluation. DFP lazy programs have the property of always evaluating a sufficient and necessary result. The infinite sequence generator is used to demonstrate the eager-lazy program transformation and the execution of the lazy programs.

  10. Mining Maximal Frequent Patterns in a Unidirectional FP-tree

    Institute of Scientific and Technical Information of China (English)

    SONG Jing-jing; LIU Rui-xin; WANG Yan; JIANG Bao-qing

    2006-01-01

    Becausemining complete set of frequent patterns from dense database could be impractical, an interesting alternative has been proposed recently. Instead of mining the complete set of frequent patterns, the new model only finds out the maximal frequent patterns, which can generate all frequent patterns. FP-growth algorithm is one of the most efficient frequent-pattern mining methods published so far. However,because FP-tree and conditional FP-trees must be two-way traversable, a great deal memory is needed in process of mining. This paper proposes an efficient algorithm Unid_FP-Max for mining maximal frequent patterns based on unidirectional FP-tree. Because of generation method of unidirectional FP-tree and conditional unidirectional FP-trees, the algorithm reduces the space consumption to the fullest extent. With the development of two techniques:single path pruning and header table pruning which can cut down many conditional unidirectional FP-trees generated recursively in mining process, Unid_ FP-Max further lowers the expense of time and space.

  11. Cyclic Codes Over Fp +uFp +vFp%环F_p+uF_p+vF_p上循环码

    Institute of Scientific and Technical Information of China (English)

    唐刚; 许小芳

    2012-01-01

    本文讨论了有限非链环R=Fp+uFp+vFp上的循环码.通过环R上的循环码与多项式环Rn=(Fp+uFp+vFp)[x]/(xn-1)的理想的对应关系给出了R上循环码的刻画.最后定义了一个Gray映射,并刻画了R上的循环码在该映射下的像.%In this paper, cyclic codes over the ring R=Fp +uFp +vFp are discussed, nite chain ring. By using the corresponding relationship between the cyclic codes over the ring R. = (Fp + uFp + vFp ) [x]/(xn- 1 ) cyclic codes over the ring R are characterized. tained and the image of cyclic codes over the ring R is characterized. where the ring R is not a firing R and the idealsin the Finally, a Gray-map is obtained and the image of cyclic codes over the ring R is characterized.

  12. Antitumor effects of FP3 in combination with capecitabine on PDTT xenograft models of primary colon carcinoma and related lymphatic and hepatic metastases.

    Science.gov (United States)

    Jin, Ketao; Lan, Huanrong; Xie, Bojian; He, Kuifeng; Xu, Zhenzhen; Li, Guangliang; Han, Na; Teng, Lisong; Cao, Feilin

    2012-07-01

    FP3 is an engineered protein which contains the extracellular domain 2 of VEGF receptor 1 (Flt-1) and extracellular domain 3 and 4 of VEGF receptor 2 (Flk-1, KDR) fused to the Fc portion of human immunoglobulin G 1. Previous studies demonstrated its antiangiogenic effects in vitro and in vivo, and its antitumor activity in vivo. In this study, patient-derived tumor tissue (PDTT) xenograft models of primary colon carcinoma and lymphatic and hepatic metastases were established for assessment of the antitumor activity of FP3 in combination with capecitabine. Xenografts were treated with FP3, capecitabine, alone or in combination. After tumor growth was confirmed, volume and microvessel density in tumors were evaluated. Levels of VEGF, and PCNA in the tumor were examined by immunohistonchamical staining, level of thymidine phosphorylase (TP) was examined by ELISA, and levels of related cell signaling pathways proteins expression were examined by western blotting. FP3 in combination with capecitabine showed significant antitumor activity in three xenograft models (primary colon carcinoma, lymphatic metastasis, and hepatic metastasis). The microvessel density in tumor tissues treated with FP3 in combination with capecitabine was lower than that of the control. Antitumor activity of FP3 in combination with capecitabine was significantly higher than that of each agent alone in three xenograft models (primary colon carcinoma, lymphatic metastasis, and hepatic metastasis). This study indicated that addition of FP3 to capecitabine significantly improved tumor growth inhibition in the PDTT xenograft models of primary colon carcinoma and lymphatic and hepatic metastases.

  13. An improved radiosynthesis of the muscarinic M2 radiopharmaceutical, [{sup 18}F]FP-TZTP

    Energy Technology Data Exchange (ETDEWEB)

    Oosten, Erik M. van [Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6 (Canada); PET Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada); Wilson, Alan A.; Stephenson, Karin A. [PET Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada); Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada); Mamo, David C. [PET Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada); Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada); Geriatric Mental Health Program, Centre for Addiction and Mental Health, 1001 Queen Street West, Toronto, Ontario, M6J 1H4 (Canada); Pollock, Bruce G.; Mulsant, Benoit H. [Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada); Geriatric Mental Health Program, Centre for Addiction and Mental Health, 1001 Queen Street West, Toronto, Ontario, M6J 1H4 (Canada); Yudin, Andrei K. [Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6 (Canada); Houle, Sylvain [PET Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada); Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada); Vasdev, Neil [PET Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada); Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada)], E-mail: neil.vasdev@camhpet.ca

    2009-04-15

    The radioligand 3-(4-(3-[{sup 18}F]fluoropropylthio)-1,2,5-thiadiazol-3-yl)-1-methyl-1,2,5, 6-tetrahydropyridine ([{sup 18}F]FP-TZTP) is an agonist with specificity towards subtype 2 of muscarinic acetylcholine (M2) receptors. It is currently the only radiotracer available for imaging M2 receptors in human subjects with positron emission tomography. The present study reports on an improved method for the synthesis of [{sup 18}F]FP-TZTP, automated using a GE TRACERlab{sup TM} FX{sub FN} radiosynthesis module. A key facet was the use of a new precursor, 3-(4-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)-1,2,5-thiadiazol-3-ylthio) propyl 4-methylbenzenesulfonate. The precursor was fluorinated via nucleophilic displacement of the tosyloxy group by potassium cryptand [{sup 18}F]fluoride (K[{sup 18}F]/K{sub 222}) in CH{sub 3}CN at 80 deg. C for 5 min, and purified by HPLC. Formulated [{sup 18}F]FP-TZTP was prepared in an uncorrected radiochemical yield of 29{+-}4%, with a specific activity of 138{+-}41 GBq/{mu}mol (3732{+-}1109 mCi/{mu}mol) at the end of synthesis (35 min; n=3). This methodology offers higher yields, faster synthesis times, an optimized precursor, and simpler automation than previously reported.

  14. Stable expression of lipocalin-type prostaglandin D synthase in cultured preadipocytes impairs adipogenesis program independently of endogenous prostanoids

    Energy Technology Data Exchange (ETDEWEB)

    Hossain, Mohammad Salim; Chowdhury, Abu Asad; Rahman, Mohammad Sharifur [Department of Life Science and Biotechnology, Shimane University, 1060 Nishikawatsu-cho, Matsue, Shimane 690-8504 (Japan); Nishimura, Kohji [Department of Molecular and Functional Genomics, Center for Integrated Research in Science, Shimane University, 1060 Nishikawatsu-cho, Matsue, Shimane 690-8504 (Japan); Jisaka, Mitsuo; Nagaya, Tsutomu [Department of Life Science and Biotechnology, Shimane University, 1060 Nishikawatsu-cho, Matsue, Shimane 690-8504 (Japan); Shono, Fumiaki [Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, 180 Yamashiro-cho, Tokushima-shi, Tokushima 770-8514 (Japan); Yokota, Kazushige, E-mail: yokotaka@life.shimane-u.ac.jp [Department of Life Science and Biotechnology, Shimane University, 1060 Nishikawatsu-cho, Matsue, Shimane 690-8504 (Japan)

    2012-02-15

    Lipocalin-type prostaglandin D synthase (L-PGDS) expressed preferentially in adipocytes is responsible for the synthesis of PGD{sub 2} and its non-enzymatic dehydration products, PGJ{sub 2} series, serving as pro-adipogenic factors. However, the role of L-PGDS in the regulation of adipogenesis is complex because of the occurrence of several derivatives from PGD{sub 2} and their distinct receptor subtypes as well as other functions such as a transporter of lipophilic molecules. To manipulate the expression levels of L-PGDS in cultured adipocytes, cultured preadipogenic 3T3-L1 cells were transfected stably with a mammalian expression vector having cDNA encoding murine L-PGDS oriented in the sense direction. The isolated cloned stable transfectants with L-PGDS expressed higher levels of the transcript and protein levels of L-PGDS, and synthesized PGD{sub 2} from exogenous arachidonic acid at significantly higher levels. By contrast, the synthesis of PGE{sub 2} remained unchanged, indicating no influence on the reactions of cyclooxygenase (COX) and PGE synthase. Furthermore, the ability of those transfectants to synthesize {Delta}{sup 12}-PGJ{sub 2} increased more greatly during the maturation phase. The sustained expression of L-PGDS in cultured stable transfectants hampered the storage of fats during the maturation phase of adipocytes, which was accompanied by the reduced gene expression of adipocyte-specific markers reflecting the down-regulation of the adipogenesis program. The suppressed adipogenesis was not rescued by either exogenous aspirin or peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) agonists including troglitazone and {Delta}{sup 12}-PGJ{sub 2}. Taken together, the results indicate the negative regulation of the adipogenesis program by the enhanced expression of L-PGDS through a cellular mechanism involving the interference of the PPAR{gamma} signaling pathway without the contribution of endogenous pro-adipogenic prostanoids

  15. Properties of the streptomycete temperate bacteriophage FP43.

    Science.gov (United States)

    Hahn, D R; McHenney, M A; Baltz, R H

    1991-06-01

    FP43 is a temperate bacteriophage for Streptomyces griseofuscus that forms plaques on many Streptomyces species. FP43 virions contain 56 kb of double-strand DNA that is circularly permuted and terminally redundant, and contains 65% G + C. A physical map of the FP43 genome was constructed, and the origin for headful packaging (pac) was localized to an 8.8-kb region of the genome (hft) that mediates high-frequency transduction by FP43 of plasmid pRHB101. The phage attachment site (attP), a replication origin (rep), a region that inhibits plaque formation (pin), and a 3-kb deletion (rpt) that caused a 100-fold reduction in plasmid transduction were mapped.

  16. Investigating FP Tau’s protoplanetary disk structure through modeling

    Science.gov (United States)

    Brinjikji, Marah; Espaillat, Catherine

    2017-01-01

    This project presents a study aiming to understand the structure of the protoplanetary disk around FP Tau, a very young, very low mass star in the Taurus star-forming region. We have gathered existing optical, Spitzer, Herschel and submillimeter observations to construct the spectral energy distribution (SED) of FP Tau. We have used the D’Alessio et al (2006) physically self-consistent irradiated accretion disk model including dust settling to model the disk of FP Tau. Using this method, the best fit for the SED of FP Tau is a model that includes a gap located 10-20 AU away from the star. This gap is filled with optically thin dust that separates the optically thick dust in the outer disk from the optically thick dust in the inner disk. These characteristics indicate that FP Tau’s protostellar system is best classified as a pre-transitional disk. Near-infrared interferometry in the K-Band from Willson et al 2016 indicates that FP Tau has a small gap located 10-20 AU from the star, which is consistent with the model we produced, lending further support to the pre-transitional disk interpretation. The most likely explanation for the existence of a gap in the disk is a forming planet.

  17. The Vasopressin Type-2 Receptor and Prostaglandin Receptors EP2 and EP4 can Increase Aquaporin-2 Plasma Membrane Targeting Through a cAMP Independent Pathway

    DEFF Research Database (Denmark)

    Olesen, Emma Tina Bisgaard; Moeller, Hanne Bjerregaard; Assentoft, Mette

    2016-01-01

    Apical membrane targeting of the collecting duct water channel aquaporin-2 (AQP2) is essential for body water balance. As this event is regulated by Gs coupled 7-transmembrane receptors such as the vasopressin type 2 receptor (V2R) and the prostanoid receptors EP2 and EP4, it is believed to be cA...

  18. The effect of reactive oxygen species on the synthesis of prostanoids from arachidonic acid.

    Science.gov (United States)

    Korbecki, J; Baranowska-Bosiacka, I; Gutowska, I; Chlubek, D

    2013-08-01

    Reactive oxygen species (ROS), such as hydrogen peroxide, superoxide anion radical or hydroxyl radical, play an important role in inflammation processes as well as in transduction of signals from receptors to interleukin -1β (IL-1β), tumor necrosis factor α (TNF-α) or lipopolysaccharides (LPS). NADPH oxidase increases the ROS levels, leading to inactivation of protein phosphatase 1 (PP1), protein phosphatase 2A (PP2A) and protein tyrosine phosphatase (PTP): MAPK phosphatase 1 (MKP-1). Inactivation of phosphatases results in activation of mitogen-activated protein kinase (MAPK) cascades: c-Jun N-terminal kinase (JNK), p38 and extracellular signal-regulated kinase (Erk), which, in turn, activate cytosolic phospholipase A₂ (cPLA₂). ROS cause cytoplasmic calcium influx by activation of phospholipase C (PLC) and phosphorylation of IP₃-sensitive calcium channels. ROS activate nuclear factor κB (NF-κB) via IκB kinase (IKK) through phosphoinositide 3-kinase (PI3K), tumor suppressor phosphatase and tensin homolog (PTEN) and protein kinase B (Akt/PKB) or NF-κB-inducing kinase (NIK). IKK phosphorylates NF-κB α subunit (IκBα) at Ser³². Oxidative stress inactivates NIK and IκB kinase γ subunit/NF-κB essential modulator (IKKγ/NEMO), which might cause activation of NF-κB that is independent on IKK and inhibitor of IκBα degradation, including phosphorylation of Tyr⁴² at IκBα by c-Src and spleen tyrosine kinase (Syk), phosphorylation of the domain rich in proline, glutamic acid, serine and threonine (PEST) sequence by casein kinase II and inactivation of protein tyrosine phosphatase 1B (PTP1B). NF-κB and MAPK cascades-activated transcription factor activator protein 1 (AP-1) and CREB-binding protein (CBP/p300) lead to expression of cytosolic phospholipase A₂ (cPLA₂), cyclooxygenase-2 (COX-2) and membrane-bound prostaglandin E synthase 1 (mPGES-1), and thus to increased release of arachidonic acid and production of prostaglandins, particularly

  19. The role of cyclooxygenase-2/prostanoid pathway in visceral pain induced liver stress response in rats

    Institute of Scientific and Technical Information of China (English)

    PISTON Donald; WANG Shan; FENG Yi; YE Ying-jiang; ZHOU Jing; JIANG Ke-wei; XU Feng; ZHAO Yong; CUI Zhi-rong

    2007-01-01

    Background Cyclooxygenase (COX) is the rate-limiting enzyme in the production of prostanoids from arachidonic acid.COX-2 is the inducible enzyme in the COX family, together with the prostanoids forms the COX-2/prostanoid pathway.Research showed that the COX-2/prostanoid pathway is activated in hepatic diseases and liver stress reaction, such as fibrogenesis, portal hypertension, carcinogenesis, and ischemic/reperfusion injury. But there was no report on visceral pain induced liver stress. This study was to investigate the role of the COX-2/prostanoid pathway in liver stress response in rat acute colitis visceral pain liver stress model.Methods Fifty-three male SD rats were randomly divided into Naive, Model, NS398 treatment, and Morphine treatment groups. The rat acute colitis visceral pain liver stress model was established under anesthesia by the colonic administration of 0.5 ml of 6% acetic acid using a urethral catheter. NS398 and morphine were administrated 30 minutes prior to model establishment in NS398 and Morphine treatment groups respectively. Spontaneous activities and pain behavior were counted and the extent of colonic inflammation was assessed histologically. Liver tissue levels of Glutathione-S-Transferase (GST) activity, COX-2 mRNA, prostaglandin E2 (PGE2), thromboxane B2 (TXB2) and 6-Ketone-prostaglandin F1α (6-K-PGF1α) contents were assessed.Results Thirty minutes after the colonic administration of acetic acid, a significant decrease in spontaneous activities and an increase in pain behaviors were observed in Model group (P<0.01 and P<0.05 respectively), accompanied by colonic inflammation. Liver GST activity levels significantly dropped (P<0.05). Liver COX-2 mRNA expression significantly increased, accompanied by an increase in liver concentrations of PGE2 and TXB2, but no obvious change in 6-K-PGF1α concentrations. NS398 and morphine both ameliorated post-stress liver GST activity (P<0.05 and P<0.01respectively), decreased stress

  20. Guidelines for the prevention of central venous catheter-related blood stream infections with prostanoid therapy for pulmonary arterial hypertension

    OpenAIRE

    Doran, A. K.; Ivy, D. D.; Barst, R.J.; Hill, N.; Murali, S; Benza, R. L.

    2008-01-01

    Intravenous prostanoids are the backbone of therapy for advanced pulmonary arterial hypertension (PAH) and have improved long-term outcome and quality of life. Currently, two prostanoids are approved by the US Food and Drug administration for parenteral administration: epoprostenol (Flolan) and treprostinil (Remodulin). Chronic intravenous therapy presents considerable challenges for patients and caregivers who must learn sterile preparation of the medication, operation of the pump, and care ...

  1. The role of the prostaglandin D2 receptor, DP, in eosinophil trafficking

    DEFF Research Database (Denmark)

    Schratl, Petra; Royer, Julia F; Kostenis, Evi

    2007-01-01

    Prostaglandin (PG) D2 is a major mast cell product that acts via two receptors, the D-type prostanoid (DP) and the chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) receptors. Whereas CRTH2 mediates the chemotaxis of eosinophils, basophils, and Th2 lymphocytes, the role...

  2. Pro-inflammatory and vasoconstricting prostanoid PGF2α causes no headache in man

    DEFF Research Database (Denmark)

    Antonova, Maria; Wienecke, Troels; Olesen, Jes;

    2011-01-01

    During two decades of migraine provocation studies with naturally occurring signalling molecules, vasodilators such as prostaglandin E(2), prostaglandin I(2) (prostacyclin) and prostaglandin D(2) were shown to be able to induce headache in man. To elucidate the role of inflammation and vasodilata...... and vasodilatation in the generation of headache, we investigated whether the pro-inflammatory and vasoconstricting prostanoid prostaglandin F(2α) (PGF(2α)) would cause headache in a human model of headache....

  3. CERN in FP7: very successful participation so far

    CERN Multimedia

    2009-01-01

    The first two years of the seventh Framework Programme were very successful for CERN – 27 EU projects were selected for funding in 2007 and 2008, with the total EC contribution exceeding 33 million euros.The seventh European Union Framework Programme for research, technological development and demonstration activities (FP7) started on 1 January 2007 and will cover the period from 2007 to 2013. With a total budget of 50.5 billion euros, FP7 is the largest Framework Programme in the history of the EU. FP7 consists of four major sub-programmes, referred to as "Specific Programmes": "Cooperation" is focused on collaborative research projects and is divided into 10 thematic areas. "Ideas" is a new EU programme for funding frontier research in all fields of science. "Capacities" aims at strengthening the research capacities in Europe, including research infrastructures and e-infrastructures. Finally, "People" succeeds the p...

  4. Mechanisms underlying sodium nitroprusside-induced tolerance in the mouse aorta: Role of ROS and cyclooxygenase-derived prostanoids.

    Science.gov (United States)

    Diniz, Mariana C; Olivon, Vania C; Tavares, Lívia D; Simplicio, Janaina A; Gonzaga, Natália A; de Souza, Daniele G; Bendhack, Lusiane M; Tirapelli, Carlos R; Bonaventura, Daniella

    2017-05-01

    To determine the role of reactive oxygen species (ROS) on sodium nitroprusside (SNP)-induced tolerance. Additionally, we evaluated the role of ROS on NF-κB activation and pro-inflammatory cytokines production during SNP-induced tolerance. To induce in vitro tolerance, endothelium-intact or -denuded aortic rings isolated from male Balb-c mice were incubated for 15, 30, 45 or 60min with SNP (10nmol/L). Tolerance to SNP was observed after incubation of endothelium-denuded, but not endothelium-intact aortas for 60min with this inorganic nitrate. Pre-incubation of denuded rings with tiron (superoxide anion (O2(-)) scavenger), and the NADPH oxidase inhibitors apocynin and atorvastatin reversed SNP-induced tolerance. l-NAME (non-selective NOS inhibitor) and l-arginine (NOS substrate) also prevented SNP-induced tolerance. Similarly, ibuprofen (non-selective cyclooxygenase (COX) inhibitor), nimesulide (selective COX-2 inhibitor), AH6809 (prostaglandin PGF2α receptor antagonist) or SQ29584 [PGH2/thromboxane TXA2 receptor antagonist] reversed SNP-induced tolerance. Increased ROS generation was detected in tolerant arteries and both tiron and atorvastatin reversed this response. Tiron prevented tolerance-induced increase on O2(-) and hydrogen peroxide (H2O2) levels. The increase onp65/NF-κB expression and TNF-α production in tolerant arteries was prevented by tiron. The major new finding of our study is that SNP-induced tolerance is mediated by NADPH-oxidase derived ROS and vasoconstrictor prostanoids derived from COX-2, which are capable of reducing the vasorelaxation induced by SNP. Additionally, we found that ROS mediate the activation of NF-κB and the production of TNF-α in tolerant arteries. These findings identify putative molecular mechanisms whereby SNP induces tolerance in the vasculature. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Impaired E Prostanoid2 Expression and Resistance to Prostaglandin E2 in Nasal Polyp Fibroblasts from Subjects with Aspirin-Exacerbated Respiratory Disease.

    Science.gov (United States)

    Cahill, Katherine N; Raby, Benjamin A; Zhou, Xiaobo; Guo, Feng; Thibault, Derek; Baccarelli, Andreas; Byun, Hyang-Min; Bhattacharyya, Neil; Steinke, John W; Boyce, Joshua A; Laidlaw, Tanya M

    2016-01-01

    Recurrent, rapidly growing nasal polyps are hallmarks of aspirin-exacerbated respiratory disease (AERD), although the mechanisms of polyp growth have not been identified. Fibroblasts are intimately involved in tissue remodeling, and the growth of fibroblasts is suppressed by prostaglandin E2 (PGE2), which elicits antiproliferative effects mediated through the E prostanoid (EP)2 receptor. We now report that cultured fibroblasts from the nasal polyps of subjects with AERD resist this antiproliferative effect. Fibroblasts from polyps of subjects with AERD resisted the antiproliferative actions of PGE2 and a selective EP2 agonist (P expression of the EP2 receptor protein was lower in fibroblasts from subjects with AERD than in fibroblasts from healthy control subjects and aspirin-tolerant subjects (P EP2 receptor mRNA in fibroblasts from AERD and aspirin-tolerant subjects but had no effect on cyclooxygenase-2, EP4, and microsomal PGE synthase 1 (mPGES-1) mRNA levels. Histone acetylation (H3K27ac) at the EP2 promoter correlated strongly with baseline EP2 mRNA (r = 0.80; P EP2 promotor is under epigenetic control, and one explanation for PGE2 resistance in AERD is an epigenetically mediated reduction of EP2 receptor expression, which could contribute to the refractory nasal polyposis typically observed in this syndrome.

  6. 环F_p+uF_p+…+u~kF_p上的准循环码%Quasi-cyclic codes over Fp+uFp+...+ukFp

    Institute of Scientific and Technical Information of China (English)

    李富林; 朱士信

    2009-01-01

    令R=F_p+uF_p+...+u~kF_p,文章定义了对于n=n_1p~s,环R~n_1到环F~p~kn1p 上的Gray映射,给出了该映射的性质,并由此得出了R环上指数为p~st,长为n=n_1p~s的准循环码与Fp上的准循环码一一对应,其中t|n_1,(n_1,p)=1,从而环R上的准循环码可以看作F_p上的准循环码.%Let R=F_p+uF_p +…+u~kF_p. The Gray map from R~n1 to F~p_p~kn1 is defined,and one of the propositions of this map is given. It is shown that a quasi-cyclic code of length n=n_1p~s with the index p't over R is uniquely equivalent to a quasi-cyclic code of length n=n_1p~s with the index p't over F_p, where t|n_1 ,(n_1,p = 1. Then the quasicyclic code over the ring R can be taken as the quasi-cyclic code over the ring F_p.

  7. Quality care for community-based FP / MCH.

    Science.gov (United States)

    1995-02-01

    The Regional Workshop on Quality Care for Community-based FP/MCH in Asia was organized by the Family Planning Association of Nepal (FPAN) in cooperation with JOICFP and held in Kathmandu, Nepal, December 4-9. Representatives of counterpart organizations in Bangladesh, Laos, Nepal, and the Philippines implementing the UNFPA-supported Sustainable Community-based FP/MCH Project with Special Focus on Women were included among the forty participants. Representatives of China and Vietnam as well as resource persons from Mexico and Japan also attended the event. The workshop was held with the goal of providing participants with effective strategies for promoting quality care for community-based FP/MCH activities based upon the Nepalese experience. The event also provided the opportunity for participants to share experiences, develop strategies for project sustainability, and identify strategies and action plans suitable for their particular country situations. In field trips to Panchkhal, Sunsari, and Morang where the project is being implemented in 26 villages, participants noted the strong community involvement and village leader support. They were also impressed by the communities' awareness of services provided under the project. FPAN has succeeded despite geographical and cultural difficulties in promoting fee-based services toward project sustainability. By paying nominal fees, villagers also enjoy access to drugs and services which may not have been available through the government free of charge. Participants at the end of the workshop recommended the identification of specific indicators and systems for monitoring services and activities, training and orientation at all levels to improve the skills and attitudes of health care workers, the development of potential income-generating activities, the provision of essential FP/MCH equipment, and the equal involvement of men and women at the policy and implementation levels.

  8. Revision of the JENDL FP Fission Yield Data

    Directory of Open Access Journals (Sweden)

    Katakura Jun-ichi

    2016-01-01

    Full Text Available Some fission yields data of JENDL FP Fission Yields Data File 2011 (JENDL/FPY-2011 revealed inadequacies when applied to delayed neutron related subjects. The sensitivity analyses of decay heat summation calculations also showed some problems. From these results the fission yields of JENDL/FPY-2011 have been revised. The present report describes the revision of the yield data by emphasizing the sensitivity analyses.

  9. The role of EP and TP receptors in the response to prostaglandin E2 in the aorta of WKY and spontaneously hypertensive rats

    DEFF Research Database (Denmark)

    Tang, Eva Hc; Jensen, Boye; Skøtt, Ole;

    2007-01-01

    -dependent relaxations in WKY but not in aortas of the SHR. High concentrations of PGE(2) evoked contractions predominately through the activation of thromboxane-prostanoid (TP) receptors in the WKY, but involves the dual activation EP and TP receptors in the SHR. SQ29,548, BAYu3405 and Terutroban (TP receptor...

  10. [{sup 18}F]{beta}-CIT-FP is superior to [{sup 11}C]{beta}-CIT-FP for quantitation of the dopamine transporter

    Energy Technology Data Exchange (ETDEWEB)

    Lundkvist, Camilla; Halldin, Christer; Ginovart, Nathalie; Swahn, Carl-Gunnar; Farde, Lars

    1997-10-01

    {beta}-CIT-FP [N-(3-fluoropropyl)-2{beta}-carbomethoxy-3{beta}-(4-iodophenyl)nortropane] is a cocaine analogue with high affinity for the dopamine transporter. Positron emission tomography (PET) studies with [O-methyl-{sup 11}C]{beta}-CIT-FP ([{sup 11}C]{beta}-CIT-FP) has shown that equilibrium conditions were approached but, however, not reached at the end of measurement. Moreover, metabolite studies of [{sup 11}C]{beta}-CIT-FP in monkey plasma demonstrated a lipophilic-labelled metabolite that may enter the brain. We therefore labelled {beta}-CIT-FP with fluorine-18 in a position that may avoid the formation of labelled lipophilic metabolites. The more long-lived radionuclide ({sup 18}F) was used to allow for measurements over longer time. [N-fluoropropyl-{sup 18}F]{beta}-CIT-FP ([{sup 18}F]{beta}-CIT-FP) was prepared by N-alkylation of nor-{beta}-CIT with [{sup 18}F]fluoropropyl bromide. PET studies were performed in cynomolgus monkeys. [{sup 18}F]{beta}-CIT-FP entered the brain rapidly. There was a high concentration of radioactivity in the striatum and much lower in the thalamus, neocortex, and cerebellum. The striatum-to-cerebellum ratio was about 5 at time of transient equilibrium, which occurred after 60 to 100 min. After pretreatment with GBR 12909, radioactivity in the striatum was markedly reduced, thus indicating specific [{sup 18}F]{beta}-CIT-FP binding to the dopamine transporter. The fraction of unchanged [{sup 18}F]{beta}-CIT-FP determined by HPLC was 10-15% after 140 min. No lipophilic labelled metabolites were detected. The absence of measurable lipophilic labelled metabolites and the occurrence of transient equilibrium within the time of the PET measurement indicate that [{sup 18}F]{beta}-CIT-FP is superior to [{sup 11}C]{beta}-CIT-FP as a PET radioligand for quantification of the dopamine transporter in the human brain.

  11. Inhibition of prostaglandin D2 clearance in rat hepatocytes by the thromboxane receptor antagonists daltroban and ifetroban and the thromboxane synthase inhibitor furegrelate.

    Science.gov (United States)

    Pestel, Sabine; Nath, Annegret; Jungermann, Kurt; Schieferdecker, Henrike L

    2003-08-15

    Prostanoids, i.e. prostaglandins and thromboxane, regulate liver-specific functions both in homeostasis and during defense reactions. For example, prostanoids are released from Kupffer cells, the resident liver macrophages, in response to the inflammatory mediator anaphylatoxin C5a, and mediate an enhanced glucose output from hepatocytes as energy supply. In perfused rat livers, the thromboxane receptor antagonist daltroban enhanced C5a-induced prostanoid overflow and reduced glucose output. It was the aim of this study to elucidate whether daltroban interfered with prostanoid release from Kupffer cells or prostanoid clearance by hepatocytes, and/or whether it directly influenced prostanoid-dependent glucose metabolism in these cells. In perfused rat livers, daltroban enhanced prostaglandin (PG)D(2) overflow not only after infusion of C5a (15-fold), but also after PGD(2) (10-fold). Neither daltroban nor another receptor antagonist, ifetroban, or the thromboxane synthase inhibitor furegrelate enhanced prostanoid release from Kupffer cells. In contrast, all inhibitors reduced clearance, i.e. uptake and degradation, of PGD(2) by hepatocytes: within 5 min uptake of 1 nmol/L PGD(2) was reduced from 43+/-5 fmol (controls) to 22+/-6 fmol (daltroban), 24+/-6 fmol (ifetroban) and 21+/-6 fmol (furegrelate). PGD(2) in the medium was reduced to 39+/-7% in the controls, but remained at 93+/-9%, 93+/-11% and 60+/-3% in the presence of the inhibitors. PGD(2)-dependent glucose output in the perfused liver or activation of glycogen phosphorylase in isolated hepatocytes remained unaffected by daltroban. These data clearly demonstrate that the thromboxane-inhibitors reduced PGD(2) clearance by hepatocytes, presumably by inhibition of prostanoid transport into the cells. In contrast, they did not interfere with PGD(2)-dependent glucose metabolism, suggesting an independent mechanism for the inhibition of glucose output from the liver.

  12. 基于改进的FP-tree的频繁模式挖掘算法%Frequent pattern mining algorithm based on improved FP-tree

    Institute of Scientific and Technical Information of China (English)

    李也白; 唐辉; 张淳; 贺玉明

    2011-01-01

    FP-growth is an efficient frequent pattern mining algorithm based on the data structure of FP-tree, which does not generate candidate sets. Constructing frequent pattern tree TP-tree requires to scanning data twice. What's more,transactions which only contain non-frequent items are also scanned during the second scanning. In order to solve this problem, after analyzing particularity of FP-tree deeply, this paper improved construction process of FP-tree and employed an auxiliary storage structure that bases on hash table, which saves time of searching items and enhances mining efficiency.%FP-growth算法是一种基于FP-tree数据结构的高效的频繁模式挖掘算法,它不产生候选集.构造频繁模式树FP-tree需扫描数据库两次,在第二遍扫描中还扫描了那些仅包含了非频繁项的事务,针对此问题,在深入分析了FP-tree特性的基础上,改进了FP-tree构造过程,同时用一种基于Hash表的辅助存储结构,节省了项目查找时间,提高了挖掘效率.

  13. Enhanced tumor necrosis factor suppression and cyclic adenosine monophosphate accumulation by combination of phosphodiesterase inhibitors and prostanoids

    NARCIS (Netherlands)

    Sinha, B; Semmler, J; Eisenhut, T; Eigler, A; Endres, S

    1995-01-01

    We investigated cooperative effects of phosphodiesterase (PDE) inhibitors and prostanoids on cyclic adenosine monophosphate (cAMP) accumulation and tumor necrosis factor (TNF)-alpha synthesis in human peripheral blood mononuclear cells (PBMC). PDE inhibitors alone induced only a small increase in cA

  14. Attenuation of hypoxic pulmonary vasoconstriction in acute oleic acid lung injury--significance of vasodilator prostanoids.

    Science.gov (United States)

    Yamaguchi, K; Mori, M; Kawai, A; Asano, K; Takasugi, T; Umeda, A; Yokoyama, T

    1992-01-01

    To assess a significant role of hypoxic pulmonary vasoconstriction, HPV, on maintaining the gas exchange efficiency in acute lung injury, 24 mongrel dogs were treated with intravenously injecting 0.07 ml/kg of oleic acid. Hemodynamic and gas-exchange parameters were investigated at varied inspired O2 concentration, FIO2. To know a possible contribution of vasoactive prostanoids in regulating vascular reactivity under these circumstances, observations were repeated after infusion of indomethacin. The impairment of gas exchange in injured lungs was examined by measuring the fractional retention, R, of the gas in arterial blood. For this evaluation, a normal saline containing five foreign inert gases such as sulfur hexafluoride, SF6, ethane, cyclopropane, halothane and diethyl ether was infused at a constant rate through a peripheral vein. After a steady state was established, the expired gas was collected and the samples of both arterial and mixed venous blood were simultaneously taken for the inert-gas analysis. The concentrations of the indicator gases in the samples were measured in terms of a gas chromatograph equipped with an electron capture detector for SF6 and a flame ionization detector for the other four gases. Although pulmonary vascular resistance, PVR, after injecting oleic acid at FIO2 0.60 was significantly smaller than that obtained at FIO2 0.21, cardiac output, QT as well as extravascular lung water were not different between the two conditions. R value for the indicator gas was consistently lower at FIO2 0.60 irrespective of the gas species. As increasing FIO2, R estimate concerning SF6, RSF6, rational index of the fractional blood flow perfusing shunt area, decreased significantly. Administration of indomethacin caused the rise in PVR without an appreciable change in either QT or extravascular lung water but a considerable diminution in R value for the inert gas. RSF6 after infusion of indomethacin decreased from 0.35 to 0.27, accompanied by a

  15. The soluble EP2 receptor FuEP2/Ex2 suppresses endometrial cancer cell growth in an orthotopic xenograft model in nude mice.

    Science.gov (United States)

    Takahashi, Tetsuyuki; Ogawa, Hirohisa; Izumi, Keisuke; Uehara, Hisanori

    2011-07-01

    Endometrial cancer is one of the most common gynecologic malignancies and many factors influence in its growth and development. As in many other types of cancer, prostaglandin E(2) (PGE(2)) is thought to be an accelerator of cell proliferation and endometrial cancer progression. In this study, we examined the effect of FuEP2/Ex2, a soluble decoy receptor for PGE(2) on growth of endometrial cancer cells. A stable transfectant expressing FuEP2/Ex2 was established from human endometrial cancer Ishikawa cells (Ish-FuEP2/Ex2). Ish-FuEP2/Ex2 cells expressed FuEP2/Ex2 mRNA and protein. Expression levels of E-prostanoid receptor 1 (EP1), EP2, EP3, EP4, and F-prostanoid receptor (FP) were almost the same in Ish-FuEP2/Ex2 and vector control cells. Growth rates of Ish-FuEP2/Ex2 under normal culture conditions were also similar to vector control cells, although PGE(2)-induced growth stimulation was completely inhibited in Ish-FuEP2/Ex2 or by Ish-FuEP2/Ex2 culture medium. Moreover, phosphorylation of extracellular signal-regulated kinase (ERK) and induction of cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), cyclin D1, and c-fos mRNA by PGE(2) were not observed in Ish-FuEP2/Ex2 and Ish-FuEP2/Ex2 culture medium-treated vector control cells, although they were found when treated with prostaglandin F(2α). An orthotopic xenograft model in athymic nude mice revealed that Ish-FuEP2/Ex2-injected mice had significantly decreased mean tumor area. The proportion of Ki-67-positive cells in the tumor lesion was also significantly lower in Ish-FuEP2/Ex2-injected mice. These findings suggest that an EP-targeting strategy using FuEP2/Ex2 may be of use in the treatment of endometrial cancer.

  16. Challenges in Implementing FP7 Projects in the Public Institutions

    Directory of Open Access Journals (Sweden)

    Viorel VULTURESCU

    2012-06-01

    Full Text Available National Authority for Scientific Research (ANCS and Executive Unit for Higher Education, Research and Development and Innovation Funding (UEFISCDI participate to several projects funded under the Framework Programmes, since 1998. The staff from each the two organisations participating in projects are merely the same, typically from “international cooperation” departments. In each of the two organisations, dedicated teams were set and a distinct specialization emerged. In this respect, dedicated procedures and good practices in project management were developed. Even the Framework Programs had different structures and the focused was different (e.g. knowledge creation, EU problem solving, scientific support for policies and programs, etc., the funding instruments (projects were not radically different from a Framework Program to another, so the staff could gain experience in managing this type of projects. Experience and expertise gained during this long period of time led to definition of a general framework within the two institutions and setting up of a general guideline for participation to this type of projects. The main dimensions of this framework are: project team organization, project management process, managing results and risk, organisational framework, good practices, factors which ensure success in project implementation.The paper presents a specific framework for FP 7 project implementation and how this framework is applied by both organisations, a set of rules and procedures that should be followed by any organisation, in particular governmental ones, participating in FP 7 projects and a set of good practices developed by ANCS and UEFISCDI.

  17. Efficient Incremental Maintenance of Frequent Patterns with FP-Tree

    Institute of Scientific and Technical Information of China (English)

    Xiu-Li Ma; Yun-Hai Tong; Shi-Wei Tang; Dong-Qing Yang

    2004-01-01

    Mining frequent patterns has been studied popularly in data mining area. However, little work has been done on mining patterns when the database has an influx of fresh data constantly. In these dynamic scenarios, efficient maintenance of the discovered patterns is crucial. Most existing methods need to scan the entire database repeatedly, which is an obvious disadvantage. In this paper, an efficient incremental mining algorithm, Incremental-Mining (IM), is proposed for maintenance of the frequent patterns when new incremental data come. Based on the frequent pattern tree (FP-tree) structure, IM gives a way to make the most of the things from the previous mining process, and requires scanning the original data once at most. Furthermore, IM can identify directly the differential set of frequent patterns, which may be more informative to users. Moreover, IM can deal with changing thresholds as well as changing data, thus provide a full maintenance scheme. IM has been implemented and the performance study shows it outperforms three other incremental algorithms: FUP, DB-tree and re-running frequent pattern growth (FP-growth).

  18. Comparison of MEK/ERK pathway inhibitors on the upregulation of vascular G-protein coupled receptors in rat cerebral arteries

    DEFF Research Database (Denmark)

    Sandhu, Hardip; Ansar, Saema; Edvinsson, Lars

    2010-01-01

    on translational level and increased respective contractions. The prostanoid TP receptor mediated contraction curve was left-wards shifted by organ culture. Organ culture was associated with elevated pERK1/2 in the vascular smooth muscle cells: the MEK1/2 inhibitor U0126 attenuated the endothelin ET(B) receptor...

  19. Mining φ-Frequent Itemset Using FP-Tree

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The problem of association rule mining has gained considerableprominence in the data mining community for its use as an important tool of knowledge discovery from large-scale databases. And there has been a spurt of research activities around this problem. However, traditional association rule mining may often derive many rules in which people are uninterested. This paper reports a generalization of association rule mining called φ-association rule mining. It allows people to have different interests on different itemsets that are the need of real application. Also, it can help to derive interesting rules and substantially reduce the amount of rules. An algorithm based on FP-tree for mining φ-frequent itemset is presented. It is shown by experiments that the proposed method is efficient and scalable over large databases.

  20. Transduction of plasmid DNA in Streptomyces spp. and related genera by bacteriophage FP43.

    Science.gov (United States)

    McHenney, M A; Baltz, R H

    1988-05-01

    A segment (hft) of bacteriophage FP43 DNA cloned into plasmid pIJ702 mediated high-frequency transduction of the resulting plasmid (pRHB101) by FP43 in Streptomyces griseofuscus. The transducing particles contained linear concatemers of plasmid DNA. Lysates of FP43 prepared on S. griseofuscus containing pRHB101 also transduced many other Streptomyces species, including several that restrict plaque formation by FP43 and at least two that produce restriction endonucleases that cut pRHB101 DNA. Transduction efficiencies in different species were influenced by the addition of anti-FP43 antiserum to the transduction plates, the temperature for cell growth before transduction, the multiplicity of infection, and the host on which the transducing lysate was prepared. FP43 lysates prepared on S. griseofuscus(pRHB101) also transduced species of Streptoverticillium, Chainia, and Saccharopolyspora.

  1. Prolonged survival time of sarcoma 180-bearing mice treated with lipid microspheres-entrapped antitumor marine coral prostanoids.

    Science.gov (United States)

    Honda, A; Mori, Y; Yamada, Y; Nakaike, S; Hayashi, H; Otomo, S

    1988-09-01

    Antitumor marine coral prostanoids (clavulone II and chlorovulone I) were entrapped into lipid microspheres of 0.2 micron diameter to make lipo-drugs. Daily treatment with lipo-chlorovulone I (1.6 mg/kg/day, i.p.) and lipo-clavulone II (12.5 mg/kg/day, i.p.) on days 1 through 5 markedly prolonged the survival time (135% ILS and 73% ILS, respectively) of mice inoculated with sarcoma 180 as compared with that of a corresponding dose of respective free chlorovulone I and clavulone II. These results suggest that lipid microspheres may be used as drug delivery carriers for antitumor coral prostanoids in vivo.

  2. The effect of trinitrobenzene sulfonic acid on gut-derived smooth muscle cell arachidonic acid metabolism: role of endogenous prostanoids

    Directory of Open Access Journals (Sweden)

    W. E. Longo

    1997-01-01

    Full Text Available The contribution of smooth muscle cells as a potential source of eicosanoid production during inflammatory states remains to be elucidated. We investigated the effect of trinitrobenzene sulfonic acid (TNB, a known pro-inflammatory agent, on jejunal smooth muscle cell eicosanoid production. Human gut-derived smooth muscle cells (HISM were incubated with TNB for 1 hour. Additionally, some cells were preincubated with either dimethylthiourea, or indomethacin for 1 hour before exposure to identical concentrations of TNB. Incubation with TNB led to significant increases in PGE2 and 6-keto PGF-1α release, but not leukotriene B4 release; responses which were both inhibited by dimethylthiourea and indomethacin treatment. Our results suggest that gutderived smooth muscle cells may represent an important source of proinflammatory prostanoids but not leukotrienes during inflammatory states of the intestine. The inhibition of prostanoid activity by thiourea may be mediated by suppression of cyclooxygenase activity in this cell line.

  3. Effect of volume replacement during combined experimental hemorrhagic shock and traumatic brain injury in prostanoids, brain pathology and pupil status

    Directory of Open Access Journals (Sweden)

    Fernando Campos Gomes Pinto

    2015-06-01

    Full Text Available Traumatic brain injury (TBI is the main cause of trauma-related deaths. Systemic hypotension and intracranial hypertension causes cerebral ischemia by altering metabolism of prostanoids. We describe prostanoid, pupilar and pathological response during resuscitation with hypertonic saline solution (HSS in TBI. Method Fifteen dogs were randomized in three groups according to resuscitation after TBI (control group; lactated Ringer’s (LR group and HSS group, with measurement of thromboxane, prostaglandin, macroscopic and microscopic pathological evaluation and pupil evaluation.Result Concentration of prostaglandin is greater in the cerebral venous blood than in plasma and the opposite happens with concentration of thromboxane. Pathology revealed edema in groups with the exception of group treated with HSS.Discussion and conclusion There is a balance between the concentrations of prostaglandin and thromboxane. HSS prevented the formation of cerebral edema macroscopically detectable. Pupillary reversal occurred earlier in HSS group than in LR group.

  4. Baculovirus FP25K Localization: Role of the Coiled-Coil Domain.

    Science.gov (United States)

    Garretson, Tyler A; McCoy, Jason C; Cheng, Xiao-Wen

    2016-11-01

    Two types of viruses are produced during the baculovirus life cycle: budded virus (BV) and occlusion-derived virus (ODV). A particular baculovirus protein, FP25K, is involved in the switch from BV to ODV production. Previously, FP25K from the model alphabaculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV) was shown to traffic ODV envelope proteins. However, FP25K localization and the domains involved are inconclusive. Here we used a quantitative approach to study FP25K subcellular localization during infection using an AcMNPV bacmid virus that produces a functional AcMNPV FP25K-green fluorescent protein (GFP) fusion protein. During cell infection, FP25K-GFP localized primarily to the cytoplasm, particularly amorphous structures, with a small fraction being localized in the nucleus. To investigate the sequences involved in FP25K localization, an alignment of baculovirus FP25K sequences revealed that the N-terminal putative coiled-coil domain is present in all alphabaculoviruses but absent in betabaculoviruses. Structural prediction indicated a strong relatedness of AcMNPV FP25K to long interspersed element 1 (LINE-1) open reading frame 1 protein (ORF1p), which contains an N-terminal coiled-coil domain responsible for cytoplasmic retention. Point mutations and deletions of this domain lead to a change in AcMNPV FP25K localization from cytoplasmic to nuclear. The coiled-coil and C-terminal deletion viruses increased BV production. Furthermore, a betabaculovirus FP25K protein lacking this N-terminal coiled-coil domain localized predominantly to the nucleus and exhibited increased BV production. These data suggest that the acquisition of this N-terminal coiled-coil domain in FP25K is important for the evolution of alphabaculoviruses. Moreover, with the divergence of preocclusion nuclear membrane breakdown in betabaculoviruses and membrane integrity in alphabaculoviruses, this domain represents an alphabaculovirus adaptation for nuclear trafficking

  5. Biodiversity monitoring in Europe: the EU FP7 EBONE project. European biodiversity observation NEtwork

    CSIR Research Space (South Africa)

    Lück-Vogel, Melanie

    2008-09-01

    Full Text Available submission Presentation Poster presentation A) Title Biodiversity Monitoring in Europe: The EU FP7 EBONE project European Biodiversity Observation NEtwork B) Short title EBONE - European Biodiversity Observation NEtwork C) Author(s) Vogel, M. (1..., South Africa F) Biodiversity Monitoring in Europe: The EU FP7 EBONE project European Biodiversity Observation NEtwork On April 1st, 2008 the EU FP7 project EBONE (http://www.ebone.wur.nl/) was launched. The aim of the project...

  6. New Astrophysical Reaction Rates for 18F(p, α)15O and 18F(p, γ)19Ne

    Institute of Scientific and Technical Information of China (English)

    SHU Neng-Chuan(舒能川); D. W. Bardayan; J. C. Blackmon; CHEN Yong-Shou(陈永寿); R. L. Kozub; P. D. Parker; M. S. Smith

    2003-01-01

    The rates of the thermonuclear 18F(p, α)15O and 18F(p,γ)19Ne reactions in hot astrophysical environments are needed to understand gamma-ray emission from nova explosions. The rates for these reactions have been uncertain due to discrepancies in recent measurements, as well as to a lack of a comprehensive examination of the available structure information in the compound nucleus 19Ne. We have examined the latest experimental measurements with radioactive and stable beams, and made estimates of the unmeasured 19Ne nuclear level parameters, to generate new rates with uncertainties for these reactions. The rates are expressed as numerical values over the temperature range relevant for stellar explosions, as well as analytical expressions as functions of temperature in a format suitable for use in astrophysical simulations. Comparisons with the previous rate calculations are carried out, and the astrophysical implications are briefly discussed.

  7. Modeling of the hEP1 receptor based on the crystallographic structure of β2-adrenergic receptor and its assessment with docking studies and molecular dynamics simulation

    Directory of Open Access Journals (Sweden)

    B Zare

    2009-12-01

    Full Text Available "nIntroduction: The human EP1 (hEP1 prostanoid receptor is a G-Protein Coupled Receptor (GPCR which plays important physiological roles in some systems in the body like cardiovascular and immune systems and could be a very important target for drug design. "nMaterials and methods: To understand the molecular structure of hEP1 receptor, a homology model of the receptor was constructed from the 2.4 Å resolution crystal structure of human β2-adrenergic receptor (PDB code: 2RH1, using three different sequence alignments. The model including PGE2 inside the active site was subjected to molecular dynamics simulation. Docking studies were performed for PGE2 and 10 prostanoid analogs in the active site of the modeled receptor. Results and Discussion: The structure of modeled receptor remained stable during the 10 nanosecond(ns simulation. In the docking simulations a correlation of r2=0.74 was observed between the Ki values and the docking scores of the prostanoid compounds. The structure which was modeled in the present study can be used in the structure-based drug design, helping the rational design of novel ligands for the hEP1 receptor. "n "n 

  8. Synthesis of Air-Stable Cyclopentadienyl Fe(CO)2 (Fp) Polymers by a Host-Guest Interaction of Cyclodextrin with Air-Sensitive Fp Pendant Groups.

    Science.gov (United States)

    Zhou, Na; Peng, Liao; Salgado, Shehan; Yuan, Jinying; Wang, Xiaosong

    2017-03-13

    Host-guest chemistry is used to address the challenge of the synthesis of air-stable polymers containing air-sensitive metal complexes. The complexation of the CpFe(CO)2 (Fp) pendent group with cyclodextrin (CD) molecules created air-stable poly(Fp-methylstyrene) P(CD/FpMSt). This CD complexation resulted in dimerization of the adjacent Fp groups, which was characterized by NMR, FTIR, and cyclic voltammetry (CV) analyses. P(CD/FpMSt) was soluble in DMSO and remained stable even the solution was exposed to air for months. The host-guest chemistry accounted for the improved stability, because the Fp groups decomposed upon removal of the CD molecules using competing guest molecules. The CD-complexed polymer showed light-trigged properties, including CO release and antimicrobial activity. Host-guest chemistry of air-sensitive organometallic complexes is therefore a promising technique that can be used to broaden the scope of metal-containing polymers (MCPs) with processable novel functions.

  9. ASASSN-17fp rebrightening event and ongoing monitoring

    Science.gov (United States)

    Waagen, Elizabeth O.

    2017-05-01

    ASASSN-17fp, discovered on 2017 April 28 and classified as a helium dwarf nova, was observed to be in outburst again on May 16 after fading 2.5 magnitudes from its original outburst. Dr. Tom Marsh (University of Warwick) and Dr. Elme Breedt (University of Cambridge) requested immediate time-series coverage. Dr. Breedt wrote: "The transient was identified as a helium dwarf nova (also known as an AMCVn star) from a spectrum taken by the PESSTO survey and reported in ATel #10334. Since then, we have been observing the target using the New Technology Telescope on La Silla in Chile. We measured a photometric period of 51 minutes in the first few nights during which the object was bright at g=16.03 (Marsh et al., ATel #10354), and then it faded to about g 18. However last night [ May 16] it brightened back to g 16 again, apparently starting a second outburst. Time series observations during this bright state would be very valuable to determine whether the 51 min period we saw in earlier data returns, and whether it is the orbital period of the binary or related to the distortion of the accretion disc in outburst (superhumps). If the 51 min signal is the orbital period or close to it, this would be the helium dwarf nova with the longest orbital period known. Multiple successive outbursts are not uncommon in binaries like this..." Observers should continue to monitor ASASSN-17fp with nightly snapshots for two weeks after it fades, in case it rebrightens again. It appears to have faded, according to an observation in the AAVSO International Database by F.-J. Hambsch (HMB, Mol, Belgium), who observed it remotely from Chile on 2017 May 24.2252 UT at magnitude 19.944 CV ± 0.595. Continue nightly snapshots through June 6 at least, and if it brightens again, resume time series. Finder charts with sequence may be created using the AAVSO Variable Star Plotter (https://www.aavso.org/vsp). Observations should be submitted to the AAVSO International Databa! se. See full Alert Notice

  10. Maternal and feto-placental prostanoid responses to a single course of antenatal betamethasone.

    Science.gov (United States)

    Cho, Steve; Beharry, Kay D A; Valencia, Arwin M; Guajardo, Leonel; Nageotte, Michael P; Modanlou, Houchang D

    2005-12-01

    We tested the hypothesis that antenatal betamethasone alters prostanoid levels in the maternal and feto-placental compartments. Forty-three singleton pregnancies were studied. Group I were women treated with a single course of antenatal betamethasone and who delivered 38 weeks. Maternal and mixed cord blood; and placental samples were collected at delivery and analyzed for PGE2, PGF(2alpha), 6-ketoPGF(1alpha), and TxB2 levels. Antenatal betamethasone decreased maternal PGE2 levels with concomitant increases in the feto-placental compartment. Umbilical cord TxB2 levels in the treated group were significantly lower than the non-treated pre-term and term groups resulting in a higher 6-ketoPGF(1alpha):TxB2 ratio. Considering the regulatory role of PGE2 and PGI2 in fetal lung development and neonatal transition homeostasis, these results suggest a mechanism, at least in part, for the beneficial effects of antenatal steroids on fetal lung maturation and neonatal cardio-pulmonary homeostasis at birth.

  11. Stress Alone or associated with Ethanol Induces Prostanoid Release in Rat Aorta via α2-Adrenoceptor

    Energy Technology Data Exchange (ETDEWEB)

    Baptista, Rafaela de Fátima Ferreira [Departamento de Farmacologia - Instituto de Biociências - Universidade Estadual Paulista - UNESP - São Paulo, SP (Brazil); Laboratório de Farmacologia - Faculdade de Medicina de Marília - FAMEMA, SP (Brazil); Taipeiro, Elane de Fátima [Laboratório de Farmacologia - Faculdade de Medicina de Marília - FAMEMA, SP (Brazil); Queiroz, Regina Helena Costa [Departamento de Análise Clínica - Toxicológica e Ciência de Alimentos - Faculdade de Ciências Farmacêuticas - USP, São Paulo, SP (Brazil); Chies, Agnaldo Bruno [Departamento de Farmacologia - Instituto de Biociências - Universidade Estadual Paulista - UNESP - São Paulo, SP (Brazil); Laboratório de Farmacologia - Faculdade de Medicina de Marília - FAMEMA, SP (Brazil); Cordellini, Sandra, E-mail: cordelli@ibb.unesp.br [Departamento de Farmacologia - Instituto de Biociências - Universidade Estadual Paulista - UNESP - São Paulo, SP (Brazil)

    2014-03-15

    Stress and ethanol are both, independently, important cardiovascular risk factors. To evaluate the cardiovascular risk of ethanol consumption and stress exposure, isolated and in association, in male adult rats. Rats were separated into 4 groups: Control, ethanol (20% in drinking water for 6 weeks), stress (immobilization 1h day/5 days a week for 6 weeks) and stress/ethanol. Concentration-responses curves to noradrenaline - in the absence and presence of yohimbine, L-NAME or indomethacin - or to phenylephrine were determined in thoracic aortas with and without endothelium. EC50 and maximum response (n=8-12) were compared using two-way ANOVA/Bonferroni method. Either stress or stress in association with ethanol consumption increased the noradrenaline maximum responses in intact aortas. This hyper-reactivity was eliminated by endothelium removal or by the presence of either indomethacin or yohimbine, but was not altered by the presence of L-NAME. Meanwhile, ethanol consumption did not alter the reactivity to noradrenaline. The phenylephrine responses in aortas both with and without endothelium also remained unaffected regardless of protocol. Chronic stress increased rat aortic responses to noradrenaline. This effect is dependent upon the vascular endothelium and involves the release of vasoconstrictor prostanoids via stimulation of endothelial alpha-2 adrenoceptors. Moreover, chronic ethanol consumption appeared to neither influence noradrenaline responses in rat thoracic aorta, nor did it modify the increase of such responses observed as a consequence of stress exposure.

  12. Stress Alone or associated with Ethanol Induces Prostanoid Release in Rat Aorta via α2-Adrenoceptor

    Science.gov (United States)

    Baptista, Rafaela de Fátima Ferreira; Taipeiro, Elane de Fátima; Queiroz, Regina Helena Costa; Chies, Agnaldo Bruno; Cordellini, Sandra

    2014-01-01

    Background Stress and ethanol are both, independently, important cardiovascular risk factors. Objective To evaluate the cardiovascular risk of ethanol consumption and stress exposure, isolated and in association, in male adult rats. Methods Rats were separated into 4 groups: Control, ethanol (20% in drinking water for 6 weeks), stress (immobilization 1h day/5 days a week for 6 weeks) and stress/ethanol. Concentration-responses curves to noradrenaline - in the absence and presence of yohimbine, L-NAME or indomethacin - or to phenylephrine were determined in thoracic aortas with and without endothelium. EC50 and maximum response (n=8-12) were compared using two-way ANOVA/Bonferroni method. Results Either stress or stress in association with ethanol consumption increased the noradrenaline maximum responses in intact aortas. This hyper-reactivity was eliminated by endothelium removal or by the presence of either indomethacin or yohimbine, but was not altered by the presence of L-NAME. Meanwhile, ethanol consumption did not alter the reactivity to noradrenaline. The phenylephrine responses in aortas both with and without endothelium also remained unaffected regardless of protocol. Conclusion Chronic stress increased rat aortic responses to noradrenaline. This effect is dependent upon the vascular endothelium and involves the release of vasoconstrictor prostanoids via stimulation of endothelial alpha-2 adrenoceptors. Moreover, chronic ethanol consumption appeared to neither influence noradrenaline responses in rat thoracic aorta, nor did it modify the increase of such responses observed as a consequence of stress exposure. PMID:24676223

  13. Tritium labeled amino acid conjugates of prostaglandins and thromboxanes as labeled ligands in prostanoid radioimmunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Sautebin, L.; Kindahl, H.; Kumlin, M.; Granstroem, E.

    1985-09-01

    Conjugates of prostaglandins and thromboxanes with tritium labeled amino acids were prepared and employed as labeled ligands in prostaglandin and thromboxane radioimmunoassays. Assays for PGF2 alpha, 15-keto-13, 14-dihydro-PGF2 alpha, TXB2 and 15-keto-13,14-dihydro-TXB2 were evaluated in comparative studies using either these heterologous ligands or the corresponding homologous tritiated eicosanoid as tracers. Binding properties for the respective antibodies were found to be similar using either tracer. Three biological studies were also conducted, viz. study of the release of TXB2 during collagen induced platelet aggregation, of 15-keto-13,14-dihydro-TXB2 during guinea pig pulmonary anaphylaxis, and of PGF2 alpha during bovine luteolysis. The analyses gave comparable results using either the heterologous or the homologous assay. Thus, this type of labeled prostanoid conjugates may serve as a convenient alternative to homologous tracers in radioimmunoassay. Heterologous tracers may even in certain cases provide the only simple solution to the problem of preparing a labeled ligand of high specific activity.

  14. Research of Improved FP-Growth Algorithm in Association Rules Mining

    Directory of Open Access Journals (Sweden)

    Yi Zeng

    2015-01-01

    with FP-Growth algorithm. Experimental results show that Painting-Growth algorithm is more than 1050 and N Painting-Growth algorithm is less than 10000 in data volume; the performance of the two kinds of improved algorithms is better than that of FP-Growth algorithm.

  15. Current Situations of the Integration of RTIs Prevention and Treatment into Routine FP Program

    Institute of Scientific and Technical Information of China (English)

    Li-xia DOU; Wei YUAN; Meng-ye PENG; Er-sheng GAO

    2007-01-01

    Objective To understand the current situation of the integration of reproductive tract infections (RTIs) prevention and treatment into routine Family planning (FP) program. Methods Literature review, in depth interview and focus group discussion were employed to collect the related information. Questionnaire survey was conducted in 59 county level FP facilities. Results Both central and local governments provide policy supports to RTIs prevention and treatment. Nearly 98.3% of local FP facilities had integrated this work into their routine FP program. A comprehensive network system of family planning has been established in China and there were plenty of FP human resources. The existing FP resource should be effectively used, which could produce great social benefit if RTIs prevention and treatment be integrated into routine FP program. However, some problems still need to be solved in the integrated program, such as insufficient finance support, low quality of service, lack of co-operations between different sectors, etc. Conclusion It is possible and feasible to develop RTIs controlling projects in the family planning system. However, intensive training and close co-operation need to be applied respectively into FP staffs and relative departments.

  16. Gaseous decontamination for major cp, fp and tru

    Energy Technology Data Exchange (ETDEWEB)

    Tatenuma, K.; Hishinuma, T.; Isoyama, N.; Noguchi, T. [Kaken Co. Mito-Institute, Ibaraki (Japan); Suzuki, M. [Tokyo Institute of Technology, Tokyo (Japan)

    1999-07-01

    As an effective decontamination based on dry-base treatment, we have developed two types practical gaseous decontamination technologies, one is based on carbonylation and fluorination reactions using several types of chemically reactive plasmas which have the performances and high efficiencies to decontaminate simultaneously the contaminants of major CP, FP and TRU, and another is based on fluorination reaction using fluoric reagent (i e., ClF{sub 3}, BrF{sub 5}, IF{sub 7}, etc.) to decontaminate the contaminants of major F P and TRU. In this study, it was verified that all of the chemically reactive plasmas of five types, which are electron cyclotron resonance, direct current, radio frequency, down stream micro wave and corona discharge, have high decontamination efficiencies of {sup 60}Co and uranium, and on the other hand the result of highly reactive gas decontamination using ClF{sub 3} as fluoric reagent showed that the contaminants of UF{sub 6} centrifugal concentrator were mostly cleaned up to non-radioactive materials under the treatment conditions of ambient temperature, short time and reduced pressure. The developed gas-phase decontamination technology based on volumes of waste created each year or non-incinerable radioactive waste. (author)

  17. FP7 FUPOL PROJECT – INNOVATION IN POLICY SCIENCE

    Directory of Open Access Journals (Sweden)

    Egils Ginters

    2013-06-01

    Full Text Available Mathematically justified planning of policy is extremely important because any wrong decision can lead to serious consequences. It is no secret that mathematical modelling and other advanced analytical methods are rarely used for policy planning and decision impact forecasting because those require specific knowledge. The FP7 FUPOL project aims at a completely new approach to traditional policy analysis providing direct access for policy decision makers to domain uses cases modelling and verification on FUPOL Simulator and visualisation of the results in the form suitable for beneficiaries. Policy domain uses cases models are versatile, therefore architecture of the simulator must fit to the requirements of complexity and usability that determines involving heterogeneous agent-based and system dynamics simulation technologies and distributed simulation. The article deals with FUPOL approach in policy modelling and simulation, simulator designing, and sustainability assessment of provided technology. The FUPOL approach promotes simultaneously running of heterogeneous use case simulation models enhancing performance of simulation session. Belonging to open source spreads potential users’ network thus reducing errors in simulation and also in policy decision making. Web services SOA based architecture enhances integration with other decision making and service tools.

  18. Research Progress on F-P Interference—Based Fiber-Optic Sensors

    Science.gov (United States)

    Huang, Yi Wen; Tao, Jin; Huang, Xu Guang

    2016-01-01

    We review our works on Fabry-Perot (F-P) interferometric fiber-optic sensors with various applications. We give a general model of F-P interferometric optical fiber sensors including diffraction loss caused by the beam divergence and the Gouy phase shift. Based on different structures of an F-P cavity formed on the end of a single-mode fiber, the F-P interferometric optical sensor has been extended to measurements of the refractive index (RI) of liquids and solids, temperature as well as small displacement. The RI of liquids and solids can be obtained by monitoring the fringe contrast related to Fresnel reflections, while the ambient temperature and small displacement can be obtained by monitoring the wavelength shift of the interference fringes. The F-P interferometric fiber-optic sensors can be used for many scientific and technological applications. PMID:27598173

  19. Projection effects on the FP thickness: a Monte-Carlo exploration

    CERN Document Server

    Lanzoni, B

    2003-01-01

    We study the contribution of projection effects to the intrinsic thickness of the Fundamental Plane (FP) of elliptical galaxies. The Monte-Carlo mapping technique between model properties and observed quantities, introduced by Bertin, Ciotti, and Del Principe (2002), is extended to oblate, two-integrals galaxy models, with non-homologous density profiles, adjustable flattening, variable amount of ordered rotational support, and for which all the relevant projected dynamical quantities can be expressed in fully analytical way. In agreement with previous works, it is found that projection effects move models not exactly parallel to the edge-on FP, by an amount that can be as large as the observed FP thickness. The statistical contribution of projection effects to the FP thickness is however marginal, and the estimated physical FP rms thickness is ~90% of the observed one (when corrected for measurement errors).

  20. Research Progress on F-P Interference-Based Fiber-Optic Sensors.

    Science.gov (United States)

    Huang, Yi Wen; Tao, Jin; Huang, Xu Guang

    2016-01-01

    We review our works on Fabry-Perot (F-P) interferometric fiber-optic sensors with various applications. We give a general model of F-P interferometric optical fiber sensors including diffraction loss caused by the beam divergence and the Gouy phase shift. Based on different structures of an F-P cavity formed on the end of a single-mode fiber, the F-P interferometric optical sensor has been extended to measurements of the refractive index (RI) of liquids and solids, temperature as well as small displacement. The RI of liquids and solids can be obtained by monitoring the fringe contrast related to Fresnel reflections, while the ambient temperature and small displacement can be obtained by monitoring the wavelength shift of the interference fringes. The F-P interferometric fiber-optic sensors can be used for many scientific and technological applications.

  1. Cloning and expression of the rabbit prostaglandin EP2 receptor

    OpenAIRE

    Guan, Youfei; Stillman, Brett A.; Zhang, Yahua; Schneider, André; Saito, Osamu; Davis, Linda S.; Redha, Reyadh; Breyer, Richard M.; Breyer, Matthew D.

    2002-01-01

    Background Prostaglandin E2 (PGE2) has multiple physiologic roles mediated by G protein coupled receptors designated E-prostanoid, or "EP" receptors. Evidence supports an important role for the EP2 receptor in regulating fertility, vascular tone and renal function. Results The full-length rabbit EP2 receptor cDNA was cloned. The encoded polypeptide contains 361 amino acid residues with seven hydrophobic domains. COS-1 cells expressing the cloned rabbit EP2 exhibited specific [3H]PGE2 binding ...

  2. Autocatalytic nitration of prostaglandin endoperoxide synthase-2 by nitrite inhibits prostanoid formation in rat alveolar macrophages.

    Science.gov (United States)

    Schildknecht, Stefan; Karreman, Christiaan; Daiber, Andreas; Zhao, Cheng; Hamacher, Jürg; Perlman, David; Jung, Birgit; van der Loo, Bernd; O'Connor, Peter; Leist, Marcel; Ullrich, Volker; Bachschmid, Markus Michael

    2012-11-15

    Prostaglandin endoperoxide H(2) synthase (PGHS) is a well-known target for peroxynitrite-mediated nitration. In several experimental macrophage models, however, the relatively late onset of nitration failed to coincide with the early peak of endogenous peroxynitrite formation. In the present work, we aimed to identify an alternative, peroxynitrite-independent mechanism, responsible for the observed nitration and inactivation of PGHS-2 in an inflammatory cell model. In primary rat alveolar macrophages stimulated with lipopolysaccharide (LPS), PGHS-2 activity was suppressed after 12 h, although the prostaglandin endoperoxide H(2) synthase (PGHS-2) protein was still present. This coincided with a nitration of the enzyme. Coincubation with a nitric oxide synthase-2 (NOS-2) inhibitor preserved PGHS-2 nitration and at the same time restored thromboxane A(2) (TxA(2)) synthesis in the cells. Formation of reactive oxygen species (ROS) was maximal at 4 h and then returned to baseline levels. Nitrite (NO(2)(-)) production occurred later than ROS generation. This rendered generation of peroxynitrite and the nitration of PGHS-2 unlikely. We found that the nitrating agent was formed from NO(2)(-), independent from superoxide ((•)O(2)(-)). Purified PGHS-2 treated with NO(2)(-) was selectively nitrated on the active site Tyr(371), as identified by mass spectrometry (MS). Exposure to peroxynitrite resulted in the nitration not only of Tyr(371), but also of other tyrosines (Tyr). The data presented here point to an autocatalytic nitration of PGHS-2 by NO(2)(-), catalyzed by the enzyme's endogenous peroxidase activity and indicate a potential involvement of this mechanism in the termination of prostanoid formation under inflammatory conditions.

  3. Procedural safety of a fully implantable intravenous prostanoid pump for pulmonary hypertension.

    Science.gov (United States)

    Richter, Manuel J; Ewert, Ralf; Warnke, Christian; Gall, Henning; Classen, Simon; Grimminger, Friedrich; Mayer, Eckhard; Seeger, Werner; Ghofrani, Hossein-Ardeschir

    2017-03-01

    In patients with severe pulmonary arterial hypertension, subcutaneous or catheter-based intravenous application of prostanoids carries a risk of local side effects or systemic infections, which limits their use and acceptance. Recently, a fully implantable pump for continuous application of intravenous treprostinil was approved in Germany. However, surgery is a major risk for patients with severe pulmonary arterial hypertension. The purpose of this study was to investigate the safety of a fully implantable pump inserted under local or general anesthesia in patients with severe pulmonary hypertension. All patients with pulmonary hypertension undergoing pump implantation for the continuous application of intravenous treprostinil were included from two German centers. Surgery was performed under local or general anesthesia according to the protocol of the recruiting center. Intra-operative safety and in-hospital complications were analyzed for the two different implantation regimens. In total, 51 patients were included. No major intra-operative complications were recorded. During the observation period, two patients died of progressive right heart failure, and two patients required treatment in the intensive care unit for acute right heart decompensation and respiratory failure. In total, major complications occurred in 8 out of 51 patients. Our observational study provides preliminary evidence supporting the procedural safety of a fully implantable pump inserted under local or general anesthesia for patients with severe pulmonary hypertension. The observation of major complications in a subset of patients requires extensive pre- and post-operative assessments. Future trials are required to provide further evidence for the long-term safety and efficacy of the pump using this approach.

  4. Sodium molybdate prevents hypertension and vascular prostanoid imbalance in fructose-overloaded rats.

    Science.gov (United States)

    Peredo, H A; Andrade, V; Donoso, A S; Lee, H J; Puyó, A M

    2013-10-01

    (1) Fructose (F) overload produces elevated blood pressure (BP), hyperglycaemia, hypertriglyceridemia and insulin resistance, resembling human metabolic syndrome. Previously, we found altered vascular prostanoid (PR) production in this model. (2) Sodium molybdate (Mo), as well as sodium tungstate, causes insulin-like effects and normalizes plasma glucose levels in streptozotocin-treated diabetic rats. We studied the effects of Mo on BP, metabolic parameters and release of PR from the mesenteric vascular bed (MVB) in F-overloaded rats. (3) Four groups of male Sprague-Dawley rats were analysed: Control, tap water to drink; F, F solution 10% W/V to drink; CMo, Mo 100 mg kg day(-1) and FMo, both treatments. After 9 weeks, the animals were killed and MVBs removed and the released PRs measured. (4) F increased BP, glycemia, triglyceridemia and insulinemia. Mo treatment prevented the increases in BP and glycemia, but did not modify triglyceridemia or insulinemia. In addition, Mo decreased BP in controls. (5) Prostaglandins (PG) F2 alpha and E2, PG 6-ketoF1 alpha and thromboxane (TX) B2 , as well as inactive metabolites of prostacyclin (PGI2 ) and TXA2 were detected. F decreased the production of vasodilator PRs PGI2 and PGE2 in MVB. Mo prevented these alterations and increased PGE2 in controls. Vasoconstrict or PRs PGF2 alpha and TXA2 release was not modified. (6) Mo treatment, beyond its known lowering effect on glycemia, prevents the reduction in the vascular release of vasodilator PR observed in this model. This could be one of the mechanisms by which Mo avoids the increase in BP caused by F overload in the rat.

  5. Dehydroepiandrosterone (DHEA) prevents the prostanoid imbalance in mesenteric bed of fructose-induced hypertensive rats.

    Science.gov (United States)

    Peredo, Horacio A; Mayer, Marcos; Faya, Ileana R; Puyó, Ana M; Carranza, Andrea

    2008-10-01

    In previous studies we reported an altered prostanoid (PR) release-pattern in mesenteric vessels in fructose (F)-overloaded rats, an experimental model of insulin resistance and hypertension. Dehydroepiandrosterone (DHEA) and its precursor Dehydroepiandrosterone sulfate (DHEA-S) are the most abundant circulating steroid hormones produced by the adrenal and recent studies in both cells and animals suggest that DHEA may have acute non-genomic actions that mimic both metabolic and vascular actions of insulin. This study was to analyze in F-overloaded rats, the effects of DHEA treatment on arterial blood pressure and the PR production in mesenteric vessels and aorta. Male 6 week-old Sprague-Dawley rats were randomly divided in four groups: a control group (C), a DHEA (30 mg/kg/sc/48 h)-treated group (D), a fructose (10% w/v in drinking water)-fed group (F), and both treatments simultaneously group (FD). The systolic blood pressure (SBP) was measured by tail cuff method and glycemia and triglyderidemia were measured by enzymatic assays. The mesenteric beds of all groups were dissected, and incubated in Krebs solution. The PR released were measured by HPLC. F overload increased SBP and triglyceridemia and decreased the mesenteric vasodilatory PR release. DHEA treatment prevented the increment in SBP and triglyceridemia and decreased vasoconstrictor PR in F-treated rats. DHEA normalize the PGI(2)/TX ratio, diminished in F-overloaded rats, through the decrease in thromboxane (TX) production and this could be one of the mechanisms by which DHEA prevented the slight hypertension in F-animals.

  6. Differential inhibition of lipopolysaccharide-induced granulocyte aggregation and prostanoid production by emoxypin.

    Science.gov (United States)

    Kubatiev, A; Turgiev, A; Smirnov, L; Pomoynetsky, V; Dumaev, K

    1990-01-01

    Emoxypin is known to be an effective membrane-stabilizing 3-oxy-pyridine derivative. We attempted to evaluate its influence on lipopolysaccharide (LPS)-induced granulocyte aggregation and prostanoid production. Granulocytes isolated from rabbit venous blood by dextran sedimentation and Pezcoll gradient centrifugation were stirred in the aggregometer cuvette with emoxypin (5mM), indomethacin (50 microM) or their solvents at 37 degrees C for 2 min. Then S. typhimurium LPS (200 micrograms/ml) was added and the aggregation was traced for 5 min. Thromboxane B2 (TxB2), prostaglandins (PG) E, F2 alpha and 13,14-dihydro-15-keto-PGF2 alpha were determined in supernatants radioimmunochemically. Indomethacin did not affect the pattern of aggregation, whereas emoxypin virtually precluded the response. Granulocytes incubated with LPS produced by the 15th sec and 5th min 1.3 and 2.5 times as much TxB2 respectively as did the intact cells (p less than 0.01). LPS had no effect on PGE production. Fifteen-sec contact of granulocytes with LPS had no significant influence on the formation of PGF2 alpha and its 13,14-dihydro-15-keto metabolite. The amount of PGF2 alpha released into the medium by the end of the 5th min of incubation with LPS was 1.5 times higher than in the control (p less than 0.05); the level of 13,14-dihydro-15-keto-PGF2 alpha was decreased 1.6 times (p less than 0.01). Emoxypin abolished totally LPS-induced TxB2 and PGF2 alpha production. We conclude that aggregation and eicosanoid production are independent manifestations of LPS-induced rabbit granulocyte activation.

  7. Improving midwives' knowledge and skills. JICA Reproductive Health Project. MCH / FP Center.

    Science.gov (United States)

    Do Thi Mui

    1999-01-01

    The Maternal and Child Health and Family Planning (MCH/FP) Center in Nghe An Province, Vietnam, has contributed to the promotion of family planning throughout the province. The institute's effective work has led to an increase in the contraceptive prevalence rate from 57.8% in 1995 to 76.3% in 1999. In addition, the law has designated the MCH/FP Center to 1) manage the MCH/FP program in Nghe An Province; 2) provide quality contraceptives required in Nghe An Province; 3) provide MCH/FP services in Vinh City; 4) instruct and supervise MCH/FP services rendered by District Health Centers and Commune Health Centers; 5) conduct training for health personnel; 6) conduct research, evaluation and monitoring; and 7) implement national programs. In June 1997, the MCH/FP Center executed a technical cooperation project on reproductive health funded by the Japan International Cooperation Agency. One of its major objectives has been the capacity building of the MCH/FP Center for training and service as a focal point of reproductive health promotion in Nghe An Province. Overall, the training programs provided by the project have been producing good results. Primary and secondary midwives and assistant doctors who participated in the JICA-training course are very pleased to be given the chance to review their knowledge and skills and to learn new techniques, and manage high-risk cases.

  8. Structural characterization of IrisFP, an optical highlighter undergoing multiple photo-induced transformations.

    Science.gov (United States)

    Adam, Virgile; Lelimousin, Mickaël; Boehme, Susan; Desfonds, Guillaume; Nienhaus, Karin; Field, Martin J; Wiedenmann, Joerg; McSweeney, Sean; Nienhaus, G Ulrich; Bourgeois, Dominique

    2008-11-25

    Photoactivatable fluorescent proteins (FPs) are powerful fluorescent highlighters in live cell imaging and offer perspectives for optical nanoscopy and the development of biophotonic devices. Two types of photoactivation are currently being distinguished, reversible photoswitching between fluorescent and nonfluorescent forms and irreversible photoconversion. Here, we have combined crystallography and (in crystallo) spectroscopy to characterize the Phe-173-Ser mutant of the tetrameric variant of EosFP, named IrisFP, which incorporates both types of phototransformations. In its green fluorescent state, IrisFP displays reversible photoswitching, which involves cis-trans isomerization of the chromophore. Like its parent protein EosFP, IrisFP also photoconverts irreversibly to a red-emitting state under violet light because of an extension of the conjugated pi-electron system of the chromophore, accompanied by a cleavage of the polypeptide backbone. The red form of IrisFP exhibits a second reversible photoswitching process, which may also involve cis-trans isomerization of the chromophore. Therefore, IrisFP displays altogether 3 distinct photoactivation processes. The possibility to engineer and precisely control multiple phototransformations in photoactivatable FPs offers exciting perspectives for the extension of the fluorescent protein toolkit.

  9. Multiwavelength narrow linewidth erbium-doped fiber laser based on FP-LDs.

    Science.gov (United States)

    Zhang, Aiqin; Jin, Yanbing; Feng, Xinhuan; Zhou, Jingjuan; Li, Zhaohui; Guan, Bai-Ou

    2013-07-15

    In this paper, we propose and demonstrate a technique to realize multiwavelength operation in erbium-doped fiber lasers (EDFLs) by inserting two Fabry Pérot laser diodes (FP-LDs) in the laser cavity respectively in cascaded and parallel way. The FP-LDs not only act as wavelength selection elements, but also offer optical gain or loss for the operation wavelengths in the laser cavity. The gains or losses for the oscillation wavelengths obtained from FP-LDs differ with adjustment of the driving current of the FP-LDs. Thus, the utilization of the FP-LDs in the laser cavity can introduce wavelength dependent gain or loss which can effectively suppress the competition caused by the homogeneous gain broadening of the erbium-doped fiber (EDF). As a result, 16-wavelength and 20-wavelength operation with a wavelength-spacing of 1.25 nm has been achieved respectively in the cascaded and parallel FP-LDs based EDFL schemes. The measured power fluctuation of each wavelength is smaller than 0.4dB for both EDFLs. Furthermore, the injection locking of the FP-LDs ensures a narrow linewidth of the EDFL output and the linewidth is estimated to be narrower than 100 MHz for the cascaded scheme based EDFL.

  10. Autopsy validation of 123I-FP-CIT dopaminergic neuroimaging for the diagnosis of DLB

    Science.gov (United States)

    Attems, Johannes; Colloby, Sean J.; O'Brien, John T.; McKeith, Ian; Walker, Rodney; Lee, Lean; Burn, David; Lett, Debra J.; Walker, Zuzana

    2017-01-01

    Objective: To conduct a validation study of 123I-N-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) nortropane (123I-FP-CIT) SPECT dopaminergic imaging in the clinical diagnosis of dementia with Lewy bodies (DLB) with autopsy as the gold standard. Methods: Patients >60 years of age with dementia who had undergone 123I-FP-CIT imaging in research studies and who had donated their brain tissue to the Newcastle Brain Tissue Resource were included. All had structured clinical research assessments, and clinical diagnoses were applied by consensus panels using international diagnostic criteria. All underwent 123I-FP-CIT imaging at baseline, and scans were rated as normal or abnormal by blinded raters. Patients were reviewed in prospective studies and after death underwent detailed autopsy assessment, and neuropathologic diagnoses were applied with the use of standard international criteria. Results: Fifty-five patients (33 with DLB and 22 with Alzheimer disease) were included. Against autopsy diagnosis, 123I-FP-CIT had a balanced diagnostic accuracy of 86% (sensitivity 80%, specificity 92%) compared with clinical diagnosis, which had an accuracy of 79% (sensitivity 87%, specificity 72%). Among patients with DLB, 10% (3 patients) met pathologic criteria for Lewy body disease but had normal 123I-FP-CIT imaging. Conclusions: This large autopsy analysis of 123I-FP-CIT imaging in dementia demonstrates that it is a valid and accurate biomarker for DLB, and the high specificity compared with clinical diagnosis (20% higher) is clinically important. The results need to be replicated with patients recruited from a wider range of settings, including movement disorder clinics and general practice. While an abnormal 123I-FP-CIT scan strongly supports Lewy body disease, a normal scan does not exclude DLB with minimal brainstem involvement. Classification of evidence: This study provides Class I evidence that 123I-FP-CIT dopaminergic neuroimaging accurately identifies patients with DLB

  11. FACTORS AFFECTING MASS MEDIA FP PROGRAMS ON CURRENT USE OF CONTRACEPTION IN BANGLADESH

    OpenAIRE

    Islam, M. Amirul; Kabir, M.

    1998-01-01

    In this paper the significant role of mass media and factors affecting it have been investigated. . Mass media has played an important role in the success of Bangladesh family planning programs. Different mass media are employed to disseminate FP-MCH messages. Evaluation of the impact of mass media exposures on FP-MCH programs would provide new directions and strategy for its effectiveness. In this study a total of 3100 currently married women from all over Bangladesh were interviewed. The ai...

  12. FlowFP: A Bioconductor Package for Fingerprinting Flow Cytometric Data

    OpenAIRE

    Wade T. Rogers; Herbert A. Holyst

    2009-01-01

    A new software package called flowFP for the analysis of flow cytometry data is introduced. The package, which is tightly integrated with other Bioconductor software for analysis of flow cytometry, provides tools to transform raw flow cytometry data into a form suitable for direct input into conventional statistical analysis and empirical modeling software tools. The approach of flowFP is to generate a description of the multivariate probability distribution function of flow cytometry data i...

  13. Preliminary results of the PREFER FP7 Project

    Science.gov (United States)

    Fusilli, Lorenzo; Laneve, Giovanni; De Bonis, Roberto; Sebastian, Ana; Ferrucci, Fabrizio; Oliveira, Sandra

    2014-05-01

    The need to improve the information and intelligence support for forest fire prevention is widely recognized. Fire prevention is still the most cost-effective strategy when compared to firefighting and extinguishing that are costly, local, and triggered only in response to already ongoing crises. PREFER project, funded under the EU FP7 (G.A. 312931), intends to contribute at responding to such a pragmatic need of southern Europe's forests by: providing timely information products based on the exploitation of all available spacecraft sensors, offering a portfolio of products focused on pre- and post-crisis forest fire emergency, suitable for the users in the different countries of the European Mediterranean area. The PREFER Service portfolio consists of two main services: 1. Information Support to Fire Preparedness/Prevention Phase" (ISP) Service 2. Information Support to Fire Recovery/Reconstruction Phase" (ISR) Service This service is already at an advanced stage having completed the first year of activity. During this time several products have been consolidated: seasonal fuel maps; daily and seasonal fire hazard maps; seasonal risk maps; prescribed fire maps. This paper aims at presenting the preliminary results of the research activity carried out in the framework of the PREFER project, focusing, in particular, on these recalled above. As for Fire Risk and Hazard assessment, many indexes have been developed in the last years. Hardly any of them uses data derived from satellite images. The FPI index is an exception to this rule which, in addition, makes use of meteorological data. In spite of being a very complete index, the FPI still allows room for improvement which justify the interest of PREFER in it. PREFER's innovative approach to FPI will allow taking into account the effect of solar illumination conditions in determining the humidity present in the dead vegetation, and therefore its proneness to burn. PREFER innovation also focus in allowing the index to

  14. Prostaglandin EP2 receptor signaling protects human trabecular meshwork cells from apoptosis induced by ER stress through down-regulation of p53

    OpenAIRE

    Kalouche, Georges; Boucher, Céline; Coste, Annick; Debussche, Laurent; Orsini, Cécile; Baudouin, Christophe; Debeir, Thomas; Vigé, Xavier; Rostène, William

    2016-01-01

    International audience; E-prostanoid receptor subtype 2 (EP2) agonists are currently under clinical development as hypotensive agents for the treatment of ocular hypertension. However, the effects of EP2 receptor agonists on trabecular meshwork (TM) alterations leading to primary open-angle glaucoma (POAG) are still unknown. Here, we evaluated whether EP2 receptor activation exhibits protective functions on TM cell death induced by endoplasmic reticulum (ER) stress. We show that the EP2 recep...

  15. Role of nitric oxide and prostanoids in the regulation of leg blood flow and blood pressure in humans with essential hypertension: effect of high-intensity aerobic training

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Jensen, Lasse Gliemann; Thaning, Pia

    2012-01-01

    We examined the role of nitric oxide (NO) and prostanoids in the regulation of leg blood flow and systemic blood pressure before and after 8 weeks of aerobic high-intensity training in individuals with essential hypertension (n=10) and matched healthy control subjects (n=11). Hypertensive subjects...

  16. Curcumin improves prostanoid ratio in diabetic mesenteric arteries associated with cyclooxygenase-2 and NF-κB suppression

    Directory of Open Access Journals (Sweden)

    Sirada Rungseesantivanon

    2010-12-01

    Full Text Available Sirada Rungseesantivanon1, Naris Thengchaisri4, Preecha Ruangvejvorachai2, Suthiluk Patumraj31Interdepartment of Physiology, Graduate School, 2Department of Pathology, 3Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; 4Department of Companion Animal Clinical Sciences, Faculty of Veterinary Medicine, Kasetsart University, Bangkok, ThailandBackground: Curcumin, the active ingredient from turmeric rhizomes, has been shown to have a wide range of pharmacological properties including antioxidant and anti-inflammatory effects. Curcumin has been reviewed for its multiple molecular action on inhibiting tumor angiogenesis via its mechanisms of cyclooxygenase (COX-2, and vascular endothelial growth factor (VEGF inhibition. In this present study, we aimed to assess the effects of curcumin on preventing diabetes-induced vascular dysfunction in association with COX-2, nuclear factor-κB (NF-κB expression, and prostanoid production.Methods: Twelve-week-old male Wistar rats were separated into five groups: 1 diabetes with 0.9% normal saline (DM-NSS; n = 10, 2 diabetes treated with curcumin 30 mg/kg (n = 10, 3 diabetes treated with curcumin 300 mg/kg (n = 10, 4 the control with 0.9% normal saline (n = 10, and 5 the control treated with 300 mg/kg (n = 10. Daily oral feeding of curcumin was started at 6 weeks after the streptozotocin injection. Levels of 6-keto prostaglandin (PG F1α and thromboxane (TX B2 were determined from mesenteric perfusates using enzyme immunoassay kits. Protein kinase C (PKC-ßII and COX-2 with NF-κB levels were analyzed in the mesenteric arteries by immunofluorescent staining and immunohistochemistry, respectively.Results: The ratio of 6-keto-PGF1α and TXB2 was significantly decreased in DM-NSS compared with the control (P < 0.05. Double-immunofluorescent staining with specific antibodies for PKC-βII and a-smooth muscle actins showed that the diabetic mesenteric arteries contained increased

  17. Matching intermediate-term, multi-angle averages of CIRS FP1+FP3 observations for the He VMR and cloud in Saturn’s atmosphere

    Science.gov (United States)

    Serrano, Joshua; Orton, Glenn S.; Sinclair, James; Fletcher, Leigh N.

    2017-01-01

    IntroductionSaturn’s atmosphere is a complicated system that is affected by many internal and external variables. To better understand these variables and how they affect Saturn’s atmospheric system we rely on data obtained from spacecraft and Earth based observatories. For this particular study, we used data from Cassini’s Composite Infrared Spectrometer (CIRS) instrument.Currently we do not know the exact amount of helium (He) with respect to molecular hydrogen gas (H2) in Saturn’s atmosphere. This He and H2 volume mixing ratio (VMR) is extremely important in understanding the structure and evolution of Saturn’s atmosphere. The CIRS team was not able to identify reliable matching spectra with data obtained from Focal Plane 1 (FP1) and Focal Plane 3 (FP3) of the CIRS instrument.MethodsAll the data sets we have worked with range from the years 2005-2012. Each year’s data sets were organized into 6 month intervals spanning the months January-June and July-December with data for FP1 and FP3 being completely separate. Each data set is also binned by planetographic latitude.Each data point consists of a spectra wavenumber, radiance value, and an emission angle. The emission angle is then converted to the unit μ, the value of this unit is simply the cosine of the emission angle. Initially all data was binned by year, latitude, and calculated µ value. This data was then plotted as a function of radiance and wavenumber to identify areas of spectral overlap data overlap in corresponding FP1 and FP3 data sets. These data sets were then prepped to be processed by a radiative transfer retrieval algorithm called NEMESIS.ResultsFurther binning of the data sets by looking at abundance of spectra values at certain μ values allows us to increase our confidence that these data sets are populated with enough spectra for NEMESIS to work with. NEMESIS has been operating with assumed He and H2 values derived from results of other studies, this means that narrowing down a

  18. Synthesis of β-CIT、β-FP-CIT and Its Precursor nor-β-CIT%β-CIT、β-FP-CIT及其前体nor-β-CIT的合成

    Institute of Scientific and Technical Information of China (English)

    唐刚华; 唐小兰

    2001-01-01

    2-β-甲酯基-3-β-(4-碘苯基)降托烷(nor-β-CIT)是多巴胺转运蛋白正电子显像剂[11C]-2-β-甲酯基-3-β-(4-碘苯基)托品烷([11C]-β-CIT)和[18F]-N-3-氟丙基-2-β-甲酯基-3-β-(4-碘苯基)降托烷([18F]-β-FP-CIT)的前体。本实验以可卡因为原料,经水解、脱水、酯化、格氏化、碘化、脱甲基等步骤合成了nor-β-CIT,总产率为12.9%,并以nor-β-CIT为原料合成了β-CIT和β-FP-CIT,为进一步放射化学合成[11C]-β-CIT和[18F]-β-FP-CIT提供了可靠的技术路线。%[11C]-2-β-Carbomethoxy-3-β-(4-iodophenyl)tropane([11C]-β-CIT)and [18F]-N-3-fluoropropyl-2-β-carbomethoxy-3-β-(4-iodophenyl)nortropane([18F]-β-FP-CIT)are the positron imaging agents as dopamine transporters,whose precursor is 2-β-carbomethoxy-3-β-(4-iodophenyl)nortropane(nor-β-CIT).The nor-β-CIT was synthesized from the cocaine as the starting material,which was based on hydrolysis,dehydration,esterification,Grignard reaction,iodination and demethylation,the total yield from the cocaine was 12.9%.The β-CIT was synthesized from the nor-β-CIT reaction with CH3I,and the β-FP-CIT synthesized from the nor-β-CIT reaction with FCH2CH2CH2Br.The study provided a practical method for radiochemical synthesis of [11C]-β-CIT and [18F]-β-FP-CIT.

  19. Prostaglandin F receptor expression in intrauterine tissues of pregnant rats

    Science.gov (United States)

    Kanca, Halit; Yar, Atiye Seda; Helvacioğlu, Fatma; Menevşe, Sevda; Çalgüner, Engin; Erdoğan, Deniz

    2014-01-01

    In this investigation, we studied the expression and localization of rat prostaglandin F (FP) receptor in uterine tissues of rats on gestational Days 10, 15, 18, 20, 21, 21.5 and postpartal Days 1 and 3 using Western blotting analysis, real-time PCR, and immunohistochemistry. A high level of immunoreactivity was observed on gestational Days 20, 21, and 21.5 with the most significant signals found on Day 20. FP receptor protein was expressed starting on gestational Day 15, and a fluctuating unsteady increase was observed until delivery. Uterine FP receptor mRNA levels were low between Days 10 and 18 of gestation (p < 0.05). The transcript level increased significantly on Day 20 and peaked on Day 21.5 just before labor (p < 0.05). There was a positive correlation between FP receptor mRNA expression and serum estradiol levels (rs = 0.78; p < 0.01) along with serum estradiol/progesterone ratios (rs = 0.79; p < 0.01). In summary, we observed an increase FP receptor expression in rat uterus with advancing gestation, a marked elevation of expression at term, and a concominant decrease during the postpartum period. These findings indicate a role for uterine FP receptors in the mediation of uterine contractility at term. PMID:24136214

  20. Whither α-FP in the diagnosis of hepatocellular carcinoma?

    Directory of Open Access Journals (Sweden)

    Kew MC

    2015-08-01

    Full Text Available Michael C Kew1,2 1Department of Medicine, Groote Schuur Hospital, University of Cape Town, Cape Town, 2University of the Witwatersrand, Johannesburg, South Africaα-FP is an α1-globulin present in high concentration in the fetal serum of mammals. It is the dominant plasma protein in the developing embryo, and is synthesized by the embryonal liver, by the endodermal cells of the visceral yolk sac, and, in very small amounts, by the embryonal intestine.1 Approximately 80% of fetal hepatocytes synthesize and secrete α-FP. The protein has been closely conserved throughout phylogenesis, suggesting that it has functions essential to the fetus, although precisely what these functions are remains to be learned. There does, however, appear to be an inverse relationship between serum α-FP and albumin levels, suggesting that α-FP might function as fetal albumin.2 Other possible biological properties of the α1-globulin include binding to estrogens and bilirubin, immunosuppressive activity, and a growth-promoting potential.3 The serum level of the protein remains constant until week 32, when it begins to sharply decrease. After birth, production of α-FP normally remains completely repressed, and serum concentrations are correspondingly very low.

  1. Effects of zinc acexamate on blood flow and prostanoid levels in the gastric mucosa of the rat.

    Science.gov (United States)

    Bulbena, O; Esplugues, J V; Escolar, G; Navarro, C; Esplugues, J

    1989-05-01

    The effects of the new antiulcer compound zinc acexamate on blood flow and prostanoid levels in the gastric mucosa have been studied. Zinc acexamate (30 and 300 mg/kg) dose-dependently prevents the reduction induced by the perfusion of noradrenaline (3.5 micrograms/kg.min, 30 min) in gastric mucosal blood flow, as measured by 3H-aniline clearance. Zinc acexamate pretreatment also increases the levels of prostaglandin E2 in the gastric mucosa of the rat, both under control conditions and after infusion with noradrenaline. The levels of thromboxane A2 and prostacyclin were not modified by zinc acexamate. These results confirm the importance of microcirculation in pathogenesis and the idea that the antiulcer activity of zinc acexamate is due in part to its action in increasing the mechanism which defend the gastric mucosa against aggression.

  2. Exercise but not prostanoids enhance levels of vascular endothelial growth factor and other proliferative agents in human skeletal muscle interstitium

    DEFF Research Database (Denmark)

    Höffner, Lotte; Nielsen, Jens Jung; Langberg, Henning

    2003-01-01

    In the present study we examined whether exercise and prostanoids have an effect on the muscle interstitial concentration of vascular endothelial growth factor (VEGF) and on the proliferative effect of muscle interstitial fluid. Dialysate from resting and exercising human skeletal muscle, obtained...... either during control conditions or during cyclooxygenase inhibition, was examined for its content of VEGF and for its effect on endothelial cell proliferation. Microdialysis probes with high (960 kDa) and low (5 kDa) molecular-mass cut-off membranes were placed in the vastus lateralis muscle of healthy......Da dialysate from resting muscle than with perfusate and was 5.8-fold higher (P muscle. VEGF was not enhanced with exercise in the 5 kDa dialysate, yet the exercise dialysate induced a 1.9-fold higher (P

  3. Parallel FP-Growth Algorithm Based on Constraint Rule%基于规则约束的并行 FP-Growth 算法研究

    Institute of Scientific and Technical Information of China (English)

    杨向荣; 王希武

    2015-01-01

    频繁模式增长(FP-Growth)算法是一种以发现频繁项集为基础的关联规则挖掘算法,从实际应用中发现,该算法需要挖掘出全部频繁项集,导致挖掘效率不高,并且无法适应大数据挖掘。因此,在现有研究的基础上,为适应大数据挖掘,进一步提高该算法的效率,论文针对该算法存在的不足,提出一种基于规则约束的并行 FP-Grow th 算法,即在并行计算模式(SIMD-SM )下对挖掘对象进行规则约束。%Frequent-Pattern Growth Algorithm(FP-Growth) is an association rules mining algorithm based on finding frequent itemsets .According to findings from actual applications ,this algorothm need to find out all frequent itemsets .On this account the mining efficiency becomes low and it can not accommodate big date mining .So ,on the basis of existing re-search ,a parallel FP-Growth algorithm is presented to accommodate big date mining and improve the efficiency of original al-gorithm .Parallel computing model(SIMD-SM ) and constraint rules are adopted in the new algorithm .The new algorithm can find out all frequent itemsets and can deal with mass data very well .

  4. FP-Growth算法在药物相互作用系统中的应用%Application of FP-Growth algorithm in interacting system of medicine

    Institute of Scientific and Technical Information of China (English)

    王殿君; 邵宗凯

    2015-01-01

    针对联合用药多不良反应事件频发的问题,提出使用关联规则挖掘中的FP-Growth算法进行分析运算. 通过FP-Growth算法挖掘药物相互作用数据,得出了药物相互作用的规则,并将此算法成功运用到系统中. 通过对数据库中的药物数据进行分析,对药物是否可以联合用药做出判断,进而对配药工作提供决策支持. 设计并实现了静脉注射药物相互作用分析系统. 结果表明,系统可以提高药物相互作用数据查询的速度95%左右,有利于促进合理用药和用药安全.%Aimed at the adverse drug reactions resulted from the combination of drugs, the FP - Growth in association rules mining was proposed. The drug-interaction rules were obtained by using FP-Growth algo-rithm to mine the data of drug interaction, and the algorithm was applied to the system successfully. By ana-lyzing the drug data in the database, the feasibility of the drug combination could be concluded, which could provide decision support for the work of configuring drugs. Finally, the system of intravenous drug-interaction analysis system was designed. The application results show that the query speed of drug-interaction data in-creases by 95%in the system, which is conducive to rational drug use and medication safety.

  5. 3-5{mu}m F-P Tunable Filter Array based on MEMS technology

    Energy Technology Data Exchange (ETDEWEB)

    Xu Wei; Chen Sihai; Bao Shiwei; Zhou Yifan; Zhao Sangzhi; Luo Huan [College of Optoelectronic Science and Engineering, Huazhong University of Science and Technology, Wuhan 430074 (China); Meng Qinghua, E-mail: xw198877@gmail.com [Guangxi Normal University, Guilin541002 (China)

    2011-02-01

    In this paper the design, fabrication and test of a MEMS F-P filter operating in 3-5{mu}m range is presented. The initial design of micro-bridge structure was achieved through COMSOL simulation software. In the simulation, the micro-bridge could achieve a displacement of 0.6{mu}m under very low applied voltage of 30V, while still preserving good mirror parallelism. By using surface micromachining techniques, a 200 x 200 array of F-P tunable micro-bridge was fabricated. SEM photographs of the fabricated device and method of optical performance test are also introduced. This MEMS F-P tunable filter can be a potential application in spectroscopic sensing and optical communication system.

  6. The interplay of universities and industry through the FP5 network

    Energy Technology Data Exchange (ETDEWEB)

    Almendral, Juan A [Departamento de Fisica, Universidad Rey Juan Carlos, Tulipan s/n, 28933 Mostoles, Madrid (Spain); Oliveira, J G [Departamento de Fisica, Universidade de Aveiro, Campus Universitario de Santiago, 3810-193 Aveiro (Portugal); Lopez, L [Departamento de IngenierIa Telematica y TecnologIa Electronica, Universidad Rey Juan Carlos, Tulipan s/n, 28933 Mostoles, Madrid (Spain); Sanjuan, Miguel A F [Departamento de Fisica, Universidad Rey Juan Carlos, Tulipan s/n, 28933 Mostoles, Madrid (Spain); Mendes, J F F [Departamento de Fisica, Universidade de Aveiro, Campus Universitario de Santiago, 3810-193 Aveiro (Portugal)

    2007-06-15

    To improve the quality of life in a modern society it is essential to reduce the distance between basic research and applications, whose crucial roles in shaping today's society prompt us to seek their understanding. Existing studies on this subject, however, have neglected the network character of the interaction between universities and industry. Here we use state-of-the-art network theory methods to analyse this interplay in the so-called Framework Programme (FP)-an initiative which sets out the priorities for the European Union's research and technological development. In particular we study in the 5th FP (FP5) the role played by companies and scientific institutions and how they contribute to enhance the relationship between research and industry. Our approach provides quantitative evidence that while firms are size hierarchically organized, universities and research organizations keep the network from falling into pieces, paving the way for an effective knowledge transfer.

  7. receptores

    Directory of Open Access Journals (Sweden)

    Salete Regina Daronco Benetti

    2006-01-01

    Full Text Available Se trata de un estudio etnográfico, que tuvo lo objetivo de interpretar el sistema de conocimiento y del significado atribuidos a la sangre referente a la transfusión sanguínea por los donadores y receptores de un banco de sangre. Para la colecta de las informaciones se observaron los participantes y la entrevista etnográfica se realizó el análisis de dominio, taxonómicos y temáticos. Los dominios culturales fueron: la sangre es vida: fuente de vida y alimento valioso; creencias religiosas: fuentes simbólicas de apoyos; donación sanguínea: un gesto colaborador que exige cuidarse, gratifica y trae felicidad; donación sanguínea: fuente simbólica de inseguridad; estar enfermo es una condición para realizar transfusión sanguínea; transfusión sanguínea: esperanza de vida; Creencias populares: transfusión sanguínea como riesgo para la salud; donadores de sangre: personas benditas; donar y recibir sangre: como significado de felicidad. Temática: “líquido precioso que origina, sostiene, modifica la vida, provoca miedo e inseguridad”.

  8. IL-6 Overexpression in ERG-Positive Prostate Cancer Is Mediated by Prostaglandin Receptor EP2.

    Science.gov (United States)

    Merz, Constanze; von Mässenhausen, Anne; Queisser, Angela; Vogel, Wenzel; Andrén, Ove; Kirfel, Jutta; Duensing, Stefan; Perner, Sven; Nowak, Michael

    2016-04-01

    Prostate cancer is the most diagnosed cancer in men and multiple risk factors and genetic alterations have been described. The TMPRSS2-ERG fusion event and the overexpression of the transcription factor ERG are present in approximately 50% of all prostate cancer patients, however, the clinical outcome is still controversial. Prostate tumors produce various soluble factors, including the pleiotropic cytokine IL-6, regulating cellular processes such as proliferation and metastatic segregation. Here, we used prostatectomy samples in a tissue microarray format and analyzed the co-expression and the clinicopathologic data of ERG and IL-6 using immunohistochemical double staining and correlated the read-out with clinicopathologic data. Expression of ERG and IL-6 correlated strongly in prostate tissue samples. Forced expression of ERG in prostate tumor cell lines resulted in significantly increased secretion of IL-6, whereas the down-regulation of ERG decreased IL-6 secretion. By dissecting the underlying mechanism in prostate tumor cell lines we show the ERG-mediated up-regulation of the prostanoid receptors EP2 and EP3. The prostanoid receptor EP2 was overexpressed in human prostate cancer tissue. Furthermore, the proliferation rate and IL-6 secretion in DU145 cells was reduced after treatment with EP2-receptor antagonist. Collectively, our study shows that the expression of ERG in prostate cancer is linked to the expression of IL-6 mediated by the prostanoid receptor EP2.

  9. Prostaglandin E2 Prevents Hyperosmolar-Induced Human Mast Cell Activation through Prostanoid Receptors EP2 and EP4

    OpenAIRE

    Ivonne Torres-Atencio; Erola Ainsua-Enrich; Fernando de Mora; César Picado; Margarita Martín

    2014-01-01

    BACKGROUND: Mast cells play a critical role in allergic and inflammatory diseases, including exercise-induced bronchoconstriction (EIB) in asthma. The mechanism underlying EIB is probably related to increased airway fluid osmolarity that activates mast cells to the release inflammatory mediators. These mediators then act on bronchial smooth muscle to cause bronchoconstriction. In parallel, protective substances such as prostaglandin E2 (PGE2) are probably also released and could explain the r...

  10. Prostaglandin E2 induces vascular relaxation by E-prostanoid 4 receptor-mediated activation of endothelial nitric oxide synthase

    DEFF Research Database (Denmark)

    Hristovska, Ana-Marija; Rasmussen, Lasse E; Hansen, Pernille B L;

    2007-01-01

    , calyculin (10(-8) mol/L), abolished the PGE(2)-mediated relaxation. In aortic rings, PGE(2) dephosphorylated eNOS at Thr(495). Chronically catheterized eNOS(-/-) mice were hypertensive (137+/-3.6 mm Hg, n=13, versus 101+/-3.9 mm Hg, n=9) and exhibited a lower sensitivity of blood pressure reduction...

  11. Investigation on a fiber optic accelerometer based on FBG-FP interferometer

    Science.gov (United States)

    Lin, Chongyu; Luo, Hong; Xiong, Shuidong; Li, Haitao

    2014-12-01

    A fiber optic accelerometer based on fiber Bragg grating Fabry-Perot (FBG-FP) interferometer is presented. The sensor is a FBG-FP cavity which is formed with two weak fiber Bragg gratings (FBGs) in a single-mode fiber. The reflectivity of the two FBGs is 9.42% and 7.74% respectively, and the fiber between them is 10 meters long. An optical demodulation system was set up to analyze the reflected light of FBG-FP cavity. Acceleration signals of different frequencies and intensities were demodulated correctly and stably by the system. Based on analyzing the optical spectrum of weak FBG based FBG-FP cavity, we got the equivalent length of FBG-FP cavity. We used a path-matching Michelson interferometer (MI) to demodulate the acceleration signal. The visibility of the interference fringe we got was 41%~42% while the theory limit was 50%. This indicated that the difference of interferometer's two arms and the equivalent length of FBG-FP cavity were matched well. Phase generated carrier (PGC) technology was used to eliminate phase fading caused by random phase shift and Faraday rotation mirrors (FRMs) were used to eliminate polarization-induced phase fading. The accelerometer used a compliant cylinder design and its' sensitivity and frequency response were analyzed and simulated based on elastic mechanics. Experiment result showed that the accelerometer had a flat frequency response over the frequency range of 31-630Hz. The sensitivity was about 31dB (0dB=1rad/g) with fluctuation less than 1.5dB.

  12. ALGORITMA PARALEL FP-GROWTH UNTUK PENGGALIAN KAIDAH ASOSIASI PADA JARINGAN KOMPUTER

    Directory of Open Access Journals (Sweden)

    F.X. Arunanto

    2011-07-01

    Full Text Available Normal 0 false false false IN X-NONE X-NONE MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} Algoritma paralel untuk penggalian kaidah asosiasi pada dataset yang besar sangat dimungkinkan dengan tujuan utama untuk mengurangi waktu eksekusi. Semakin besarnya dataset, rata-rata jumlah item dalam sebuah transaksi dan rata-rata jumlah panjang large itemset yang digunakan akan menambah waktu eksekusi dalam penggalian kaidah asosisasi. Oleh karena itu, berbagai algoritma paralel banyak dikembangkan dengan seiringnya waktu, salah satunya adalah algoritma paralel FP-Growth secara trivial paralellization. Pada penelitian ini, algoritma paralel yang dibentuk akan diimplementasikan terhadap salah satu algoritma penggalian kaidah asosiasi yaitu algoritma FP-Growth. FP-Growth dipilihkarena memiliki banyak keuntungan dengan struktur data FP-Tree sebagai bentuk kompresi dataset dan tidak ada waktu yang terbuang untuk perulangan proses pengamatan dataset dibandingkan algoritma sebelumnnya seperti Apriori. Uji coba dilakukan di lingkungan komputer paralel berbasis jaringan komputer dengan menggunakan Pustaka Massage Passing Interface dan hasilnya membuktikan bahwa algoritma paralel FP-Growth menunjukkan performa yang lebih baik daripada algoritma FP-Growth pada komputer tunggal.

  13. The preclinical pharmacological study of dopamine transporter imaging agent 18F-FP-β-CIT

    Institute of Scientific and Technical Information of China (English)

    LI Xiaomin; CHEN Zhengping; WANG Songpei; TANG Jie; LIN Yansong; ZHU Zhaohui; FANG Ping

    2007-01-01

    The paper is to study pharmacologic characteristics of 18F-FP-β-CIT (18F-N-(3-fluoropropyl)-2β- carbomethoxy-3β- (4-iodophenyl)nortropane) as an imaging agent for dopamine transporter. The radiochemical purity of 18F-FP-β-CIT in aqueous solution was over 95% after standing at room temperature for 4h. Biodistribution displayed rapid uptake in rat brain (1.375 %ID/organ at 5min and 0.100 %ID/organ at 180 min) and the striatal uptake was 1.444,0.731, 0.397, 0.230 and 0.146 %ID/g at 5, 30, 60, 120 and 180 min, respectively. The values of striatum/cerebellum,striatum/frontal cortex and striatum / hippocampus in rat's brain at 30 min were 3.38, 2.17 and 2.40 respectively. The uptake in striatum can be blocked by β-CFT, suggesting that 18F-FP-β-CIT binds to DAT peculiarly. The compound was rapidly cleared from monkey's blood. The striatal uptake was bilaterally decreased in the left-sided lesioned PD rats, compared with normal control. Brain PET imaging studies in normal monkey showed that 18F-FP-β-CIT was concentrated in striatum. The test of undue toxicity showed that the dose received by mice was 1250 times as by human, which indicates that 18F-FP-β-CIT is very safe. So 18F-FP-β-CIT is a promising PET imaging agent for DAT with safety and validity.

  14. Research and Application on Web Information Retrieval Based on Improved FP-Growth Algorithm

    Institute of Scientific and Technical Information of China (English)

    JIAO Minghai; YAN Ping; JIANG Huiyan

    2006-01-01

    A kind of single linked lists named aggregative chain is introduced to the algorithm, thus improving the architecture of FP tree. The new FP tree is a one-way tree and only the pointers that point its parent at each node are kept. Route information of different nodes in a same item are compressed into aggregative chains so that the frequent patterns will be produced in aggregative chains without generating node links and conditional pattern bases. An example of Web key words retrieval is given to analyze and verify the frequent pattern algorithm in this paper.

  15. Experimental study on narrow spectral width FP lasers with a wavelength detuned band-pass filter

    Science.gov (United States)

    Fu, Junwei; Xi, Yanping; Li, Xun; Hong, Wei; Huang, Weiping

    2017-08-01

    In this paper, a 1310 nm InAlGaAs/InP multiple quantum well ridge waveguide FP laser with a built-in wavelength detuned band-pass filter has been fabricated and investigated in experiments. When compared to the reference FP laser fabricated in the same wafer, it is observed that the root-mean-square spectral width can be approximately reduced to half; and moreover, significant improvements on the transmission performances in terms of the power penalty at given transmission distance and the longest transmission distance at given bit error rate, have been achieved for the proposed laser at the same fabrication cost.

  16. European multicentre database of healthy controls for [(123)I]FP-CIT SPECT (ENC-DAT)

    DEFF Research Database (Denmark)

    Varrone, Andrea; Dickson, John C; Tossici-Bolt, Livia;

    2013-01-01

    Dopamine transporter (DAT) imaging with [(123)I]FP-CIT (DaTSCAN) is an established diagnostic tool in parkinsonism and dementia. Although qualitative assessment criteria are available, DAT quantification is important for research and for completion of a diagnostic evaluation. One critical aspect...... of quantification is the availability of normative data, considering possible age and gender effects on DAT availability. The aim of the European Normal Control Database of DaTSCAN (ENC-DAT) study was to generate a large database of [(123)I]FP-CIT SPECT scans in healthy controls....

  17. Prostaglandin F2alpha elevates blood pressure and promotes atherosclerosis

    DEFF Research Database (Denmark)

    Yu, Ying; Lucitt, Margaret B; Stubbe, Jane

    2009-01-01

    Little is known about prostaglandin F(2alpha) in cardiovascular homeostasis. Prostaglandin F(2alpha) dose-dependently elevates blood pressure in WT mice via activation of the F prostanoid (FP) receptor. The FP is expressed in preglomerular arterioles, renal collecting ducts, and the hypothalamus....... Deletion of the FP reduces blood pressure, coincident with a reduction in plasma renin concentration, angiotensin, and aldosterone, despite a compensatory up-regulation of AT1 receptors and an augmented hypertensive response to infused angiotensin II. Plasma and urinary osmolality are decreased in FP KOs...

  18. Simultaneous MMW generation and up-conversion for WDM-ROF systems based on FP laser

    Science.gov (United States)

    Zhang, Chan; Ning, TiGang; Li, Jing; Li, Chao; He, Xueqing; Pei, Li

    2016-10-01

    A new wavelength division multiplexing radio-over-fiber (WDM-ROF) scheme based on Fabry-Perot (FP) laser is proposed and demonstrated for simultaneous millimeter-wave (MMW) generation and up-conversion. The tunable optical comb generated by FP laser is served as a cost-effective WDM optical source in central station (CS) and it makes all-optical up-conversion process for all channels simple compared with using a DFB array. All modes from the FP laser are modulated simultaneously by a LiNbO3 Mach-Zehnder modulator (LN-MZM) then. We have systematically compared the performances of MMW generation and up-conversion using LN-MZM based on different modulation schemes. A reflective semiconductor optical amplifiers (RSOA) is used both for the downstream modulation of each channel and for the reduction of mode partition noise (MPN) induced from FP laser. In the scheme, the multiple optical carrier suppression (OCS) modulation shows the highest receiver sensitivity and smallest power penalty over long-distance delivery. In the numerical simulation, 7 WDM channels each carrying 2.5 Gb/s baseband signal have been up-converted to 60 GHz simultaneously with good performance over 25 km single mode fiber (SMF) transmission.

  19. Quantification of Azospirillum brasilense FP2 Bacteria in Wheat Roots by Strain-Specific Quantitative PCR.

    Science.gov (United States)

    Stets, Maria Isabel; Alqueres, Sylvia Maria Campbell; Souza, Emanuel Maltempi; Pedrosa, Fábio de Oliveira; Schmid, Michael; Hartmann, Anton; Cruz, Leonardo Magalhães

    2015-10-01

    Azospirillum is a rhizobacterial genus containing plant growth-promoting species associated with different crops worldwide. Azospirillum brasilense strains exhibit a growth-promoting effect by means of phytohormone production and possibly by N2 fixation. However, one of the most important factors for achieving an increase in crop yield by plant growth-promoting rhizobacteria is the survival of the inoculant in the rhizosphere, which is not always achieved. The objective of this study was to develop quantitative PCR protocols for the strain-specific quantification of A. brasilense FP2. A novel approach was applied to identify strain-specific DNA sequences based on a comparison of the genomic sequences within the same species. The draft genome sequences of A. brasilense FP2 and Sp245 were aligned, and FP2-specific regions were filtered and checked for other possible matches in public databases. Strain-specific regions were then selected to design and evaluate strain-specific primer pairs. The primer pairs AzoR2.1, AzoR2.2, AzoR5.1, AzoR5.2, and AzoR5.3 were specific for the A. brasilense FP2 strain. These primer pairs were used to monitor quantitatively the population of A. brasilense in wheat roots under sterile and nonsterile growth conditions. In addition, coinoculations with other plant growth-promoting bacteria in wheat were performed under nonsterile conditions. The results showed that A. brasilense FP2 inoculated into wheat roots is highly competitive and achieves high cell numbers (∼10(7) CFU/g [fresh weight] of root) in the rhizosphere even under nonsterile conditions and when coinoculated with other rhizobacteria, maintaining the population at rather stable levels for at least up to 13 days after inoculation. The strategy used here can be applied to other organisms whose genome sequences are available.

  20. Global scaling for semi-quantitative analysis in FP-CIT SPECT.

    Science.gov (United States)

    Kupitz, D; Apostolova, I; Lange, C; Ulrich, G; Amthauer, H; Brenner, W; Buchert, R

    2014-01-01

    Semi-quantitative characterization of dopamine transporter availability from single photon emission computed tomography (SPECT) with 123I-ioflupane (FP-CIT) is based on uptake ratios relative to a reference region. The aim of this study was to evaluate the whole brain as reference region for semi-quantitative analysis of FP-CIT SPECT. The rationale was that this might reduce statistical noise associated with the estimation of non-displaceable FP-CIT uptake. 150 FP-CIT SPECTs were categorized as neurodegenerative or non-neurodegenerative by an expert. Semi-quantitative analysis of specific binding ratios (SBR) was performed with a custom-made tool based on the Statistical Parametric Mapping software package using predefined regions of interest (ROIs) in the anatomical space of the Montreal Neurological Institute. The following reference regions were compared: predefined ROIs for frontal and occipital lobe and whole brain (without striata, thalamus and brainstem). Tracer uptake in the reference region was characterized by the mean, median or 75th percentile of its voxel intensities. The area (AUC) under the receiver operating characteristic curve was used as performance measure. The highest AUC of 0.973 was achieved by the SBR of the putamen with the 75th percentile in the whole brain as reference. The lowest AUC for the putamen SBR of 0.937 was obtained with the mean in the frontal lobe as reference. We recommend the 75th percentile in the whole brain as reference for semi-quantitative analysis in FP-CIT SPECT. This combination provided the best agreement of the semi-quantitative analysis with visual evaluation of the SPECT images by an expert and, therefore, is appropriate to support less experienced physicians.

  1. Evaluating the Latent Structure of the MMPI-2 F(p) Scale in a Forensic Sample: A Taxometric Analysis

    Science.gov (United States)

    Strong, David R.; Glassmire, David M.; Frederick, Richard I.; Greene, Roger L.

    2006-01-01

    P. A. Arbisi and Y. S. Ben-Porath (1995) originally proposed that the Infrequency Psychopathology scale, F(p), be used as the final step in an algorithm to determine the validity of a Minnesota Multiphasic Personality Inventory-2 (MMPI-2) protocol. The current study used taxometric procedures to determine the latent structure of F(p) among…

  2. Characterization of FP22, a large streptomycete bacteriophage with DNA insensitive to cleavage by many restriction enzymes.

    Science.gov (United States)

    Hahn, D R; McHenney, M A; Baltz, R H

    1990-12-01

    Bacteriophage FP22 has a very broad host range within streptomycetes and appeared to form lysogens of Streptomyces ambofaciens ATCC 15154. FP22 shared strong cross-immunity and antibody cross-reactivity with bacteriophage P23, but not with seven other streptomycete bacteriophages. FP22 particles had a head diameter of 71 nm and a tail length of 307 nm. The FP22 genome was 131 kb, which is the largest bacteriophage genome reported for streptomycetes. The G + C content of the genome was 46 mol% and restriction mapping indicated that FP22 DNA had discrete ends. NaCl- and pyrophosphate-resistant deletion mutants were readily isolated and the extent of the deletions defined at least 23 kb of dispensable DNA in two regions of the genome. The DNA was not cleaved by most restriction endonucleases (or isoschizomers) which have been identified in the streptomycetes, including the tetranucleotide cutter MboI (GATC).

  3. FP-tree association rules algorithm in recommendation system%基于FP-tree算法的推荐系统设计与实现

    Institute of Scientific and Technical Information of China (English)

    刘华; 张亚昕

    2015-01-01

    当前是信息爆炸的时代,推荐系统已成为解决当前网络信息超载的有效工具。文章针对网上书店的电子商务网站的销售特点,详细地设计了推荐系统,并利用挖掘技术中的FP-tree关联规则算法实现数据挖掘运算,很好的实现了在线推荐的系统功能。%This is the era of information explosion, recommendation system has become an effective tool for solving the current network information overload. Aiming at the characteristics of online bookstores sell e-commerce site, a detailed design of the recommendation system, and using mining techniques in FP-tree data mining association rules algorithm computation, to achieve a good online recommendation system functions.

  4. High spin structure of {sup 35}Cl and the sd-fp shell gap

    Energy Technology Data Exchange (ETDEWEB)

    Kshetri, Ritesh [Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, Kolkata 700064 (India); Saha Sarkar, M. [Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, Kolkata 700064 (India)]. E-mail: maitrayee.sahasarkar@saha.ac.in; Ray, Indrani [Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, Kolkata 700064 (India); Banerjee, P. [Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, Kolkata 700064 (India); Sarkar, S. [Department of Physics, Bengal Engineering and Science University, Shibpur, Howrah 711103 (India); Raut, Rajarshi [Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, Kolkata 700064 (India); Goswami, A. [Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, Kolkata 700064 (India); Chatterjee, J.M. [Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, Kolkata 700064 (India); Chattopadhyay, S. [Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, Kolkata 700064 (India); Datta Pramanik, U. [Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, Kolkata 700064 (India); Mukherjee, A. [Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, Kolkata 700064 (India); Dey, C.C. [Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, Kolkata 700064 (India); Bhattacharya, S. [Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, Kolkata 700064 (India); Dasmahapatra, B. [Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, Kolkata 700064 (India); Bhowal, Samit [Department of Physics, Surendranath Evening College, Kolkata 700009 (India); Gangopadhyay, G. [University of Calcutta, 92, Acharya Prafulla Chandra Road, Kolkata 700009 (India); Datta, P. [Anandamohan College, 102/1, Raja Rammohan Sarani, Kolkata 700009 (India); Jain, H.C. [Tata Institute of Fundamental Research, Mumbai 400005 (India); Bhowmik, R.K. [Inter-University Accelerator Centre, Aruna Asaf Ali Marg, New Delhi 110067 (India); Muralithar, S.; Singh, R.P.; Kumar, R. [Inter-University Accelerator Centre, Aruna Asaf Ali Marg, New Delhi 110067 (India)

    2007-01-15

    The high spin states of {sup 35}Cl have been studied by in-beam {gamma}-spectroscopy following the fusion-evaporation reaction {sup 12}C({sup 28}Si,{alpha}p){sup 35}Cl at E{sub lab}=70 and 88 MeV, using the Indian National Gamma (Clover) Array (INGA). Lifetimes of six new excited states have been estimated for the first time. To understand the underlying structure of the levels and transition mechanisms, experimental results have been compared with those from the large basis cross-shell shell model calculations. Involvement of orbitals from fp shell and squeezing of the sd-fp shell gap seem to be essential for reliable reproduction of high spin states.

  5. A Human "eFP" Browser for Generating Gene Expression Anatograms.

    Science.gov (United States)

    Patel, Rohan V; Hamanishi, Erin T; Provart, Nicholas J

    2016-01-01

    Transcriptomic studies help to further our understanding of gene function. Human transcriptomic studies tend to focus on a particular subset of tissue types or a particular disease state; however, it is possible to collate into a compendium multiple studies that have been profiled using the same expression analysis platform to provide an overview of gene expression levels in many different tissues or under different conditions. In order to increase the knowledge and understanding we gain from such studies, intuitive visualization of gene expression data in such a compendium can be useful. The Human eFP ("electronic Fluorescent Pictograph") Browser presented here is a tool for intuitive visualization of large human gene expression data sets on pictographic representations of the human body as gene expression "anatograms". Pictographic representations for new data sets may be generated easily. The Human eFP Browser can also serve as a portal to other gene-specific information through link-outs to various online resources.

  6. A flexible testing facility for high-power targets (Tiara FP7 program)

    CERN Document Server

    Fusco, Y.; Samec, K.; Kadi, Y.

    2014-01-01

    Building on recent experience in the field of applied physics, TIARA Work package n° 9 focuses on target applications for accelerators in Europe. A roadmap for target development has been derived from major achievements in the EU-FP6 and EU-FP7 programs such as the MEGAPIE and EURISOL experiments. The TIARA management board concluded that a worthwhile continuation of such projects would be in the development of a flexible material irradiation facility easily transportable and which could be installed in different laboratories. The power is limited to 100 kW in a very compact arrangement so as to obtain the best neutron economy from a moderate beam power which is more likely to be found in laboratories across Europe. The challenges posed by such a compact design and accompanying calculations are presented in the current work.

  7. Extrastriatal binding of [¹²³I]FP-CIT in the thalamus and pons

    DEFF Research Database (Denmark)

    Koch, Walter; Unterrainer, Marcus; Xiong, Guoming

    2014-01-01

    PURPOSE: Apart from binding to the dopamine transporter (DAT), [(123)I]FP-CIT shows moderate affinity for the serotonin transporter (SERT), allowing imaging of both monoamine transporters in a single imaging session in different brain areas. The aim of this study was to systematically evaluate...... error) of 8.2 ± 1.3 % for the thalamus and 6.8 ± 2.9 % for the pons was shown. CONCLUSION: The potential to evaluate extrastriatal predominant SERT binding in addition to the striatal DAT in a single imaging session was shown using a large database of [(123)I]FP-CIT scans in healthy controls. For both...

  8. Simulations on the kindling mechanism of the asFP595 fluorescent protein

    Science.gov (United States)

    Grigorenko, Bella L.; Nemukhin, Alexander V.; Savitsky, Alexander P.

    2008-02-01

    We report the results of quantum mechanical - molecular mechanical (QM/MM) simulations aiming to elucidate the mechanism of kindling of the initially non-fluorescent protein asFP595, which is a mutated variant of the chromoprotein asCP from the sea anemone Anemonia sulcata. asFP595 becomes brightly fluorescent (kindles) with emission at 595 nm in response to intense light irradiation at 568 nm. In simulations, we use the flexible effective fragment QM/MM method with the complete active space self-consistent field (CASSCF) wavefunctions in the quantum part and the AMBER force field parameters in the molecular mechanical part. We analyze the computed scans over potential energy surfaces of the ground and excited electronic states and consider details of the working hypothesis that the trans-cis isomerization of the chromophore group inside the protein is responsible for kindling.

  9. Femtosecond laser fabricated in-line micro multicavity fiber FP interferometers sensor

    Science.gov (United States)

    Tian, Ming; Lu, Ping; Chen, Li; Liu, Deming; Yang, Minghong; Zhang, Jiangshan

    2014-04-01

    A compact micro multicavity Fabry-Perot (FP) optical fiber tip sensor is presented. In the end of the single-mode fiber (SMF), we drill a short air hole with femtosecond laser, which forms a multicavity together with the fiber flat face tip. The sensor has been experimentally tested for refractive index (RI) and temperature sensing by monitoring its wavelength shift. Simultaneous measurement of both changes in the ambient temperature and the RI can be realized using the sensitivity matrix. Measurement results show that the in-line FP exhibits the gas RI sensitivity of 867.76 nm/RIU and the temperature sensitivity of 7.8 pm/°C within the range of 24-104 °C, and the device is highly stable over time.

  10. Feasibility of flat-panel volumetric computed tomography (fpVCT) in experimental small animal imaging of osteoporosis - initial experience; Erste Erfahrungen mit einem Flaechendetektor-Volumen-CT (fpVCT) in der experimentellen Osteoporosediagnostik am Kleintiermodell

    Energy Technology Data Exchange (ETDEWEB)

    Valencia, R.; Dullin, C.; Herrmann, K.P.; Kluever, I.; Zaroban, A.; Knollmann, F. [Universitaetsklinikum Goettingen (Germany). Abteilung Diagnostische Radiologie, Goettingen; Stuermer, E.K.; Sehmisch, S. [Universitaetsklinikum Goettingen (Germany). Klinik fuer Unfallchirurgie, Plastische und Wiederherstellungschirurgie; Funke, M. [Klinikum Mittelbaden, Baden-Baden (Germany). Radiologische Klinik an der Stadtklinik

    2006-10-15

    Flat-panel volumetric computed tomography (fpVCT) is a new, noninvasive CT imaging modality with increased isotropic resolution. Technical details, potential applications, and our initial experience with a fpVCT prototype scanner in the imaging of osteoporosis in a rat model are presented. To date, 21 rats have been investigated in vivo with fpVCT. Pharmacologic effects on bone mineral density (BMD) and structure were of special interest. Image evaluation focussed on the second lumbar vertebra and the left femoral bone. To validate measurement results, BMD values calculated with fpVCT were correlated with results of BMD measurements from ashing of the second lumbar vertebra and femoral bones. Our initial results show that fpVCT is capable of detecting differences in BMD between ovariectomized rats treated with estradiol and a control group with high statistical significance (p<0.05), corresponding to ashing as the gold standard. In a rat model, fpVCT imaging is especially useful in longitudinal in vivo investigations of BMD measures. Spatial resolution of up to 150 {mu}m allows imaging of the trabecular structure only in human cadaveric bones. (orig.) [German] Die Flaechendetektor-Volumen-Computertomographie (fpVCT) ist eine neuartige CT-Bildgebungstechnik, die eine gesteigerte isotrope Ortsaufloesung ermoeglicht. In dieser Arbeit wird ueber Technik, Anwendungsmoeglichkeiten und erste Erfahrungen beim Einsatz eines fpVCT-Prototyps in der experimentellen Diagnostik der Osteoporose am Rattenmodell berichtet. Bisher konnten 21 Ratten in vivo am fpVCT untersucht werden. Von besonderem Interesse waren Medikamentenwirkungen auf Knochendichte (''bone mineral density'', BMD) und -struktur. Die Auswertung der gewonnenen Bilddaten fokussierte sich auf den 2. Lendenwirbelkoerper und das linke Femur. Um die Messergebnisse zu ueberpruefen, wurden die mittels fpVCT errechneten BMD-Werte mit den Ergebnissen der Dichtemessung der veraschten 2. LWK und Femora

  11. Differential diagnosis of Parkinsonism using dual phase F 18 FP CIT PET imaging

    Energy Technology Data Exchange (ETDEWEB)

    Jin, So Young; Oh, Min Young; Ok, Seung Jun; Oh, Jung Su; Lee, Sang Ju; Chung, Sun Ju; Lee, Chong Sik; Kim, Jae Seung [Univ. of Ulsan, Seoul (Korea, Republic of)

    2012-03-15

    Dopamine transporter (DAT) imaging can demonstrate presynaptic dopaminergic neuronal loss in Parkinson's disease (PD). However, differentiating atypical parkinsonism (APD) from PD is often difficult. We investigated the usefulness of dual phase F 18 FP CIT positron emission tomography (PET) imaging in the differential diagnosis of parkinsonism. Ninety eight subjects [five normal, seven drug induced parkinsonism (DIP), five essential tremor (ET), 24 PD, 20 multiple system atrophy parkinson type (MSA-P), 13 multiple system atrophy cerebellar type (MSA-C), 13 progressive supranuclear palsy (PSP), and 11 dementia with Lewy bodies(DLB)] underwent F 18 FP CIT PET. PET images were acquired at 5 min (early phase) and 3 h (late phase) after F 18 FP CIT administration (185MBq). Regional uptake pattern of cerebral and cerebellar hemispheres was assessed on early phase images, using visual, quantitative, and statistical parametric mapping (SPM) analyses. Striatal DAT binding was normal in normal, ET, DIP, and MSA C groups, but abnormal in PD, MSA P PSP, and DLB groups. No difference was found in regional uptake on early phase images among normal DAT binding groups, except in the MSA C group. Abnormal DAT binding groups showed different regional uptake pattern on early phase images compared with PD in SPM analysis (FDR<0.05). When discriminating APD from PD, visual interpretation of the early phase image showed high diagnostic sensitivity and specificity (75.4% and 100%, respectively). Regarding the ability to distinguish specific APD, sensitivities were 81% for MSA P, 77% for MSA C, 23% for PSP, and 54.5% for DLB. Dual phase F 18 FP CIT PET imaging is useful in demonstrating striatal DAT loss in neurodegenerative parkinsonism, and also in differentiating APD, particularly MSA, from PD.

  12. Serial Femtosecond Crystallography and Ultrafast Absorption Spectroscopy of the Photoswitchable Fluorescent Protein IrisFP.

    Science.gov (United States)

    Colletier, Jacques-Philippe; Sliwa, Michel; Gallat, François-Xavier; Sugahara, Michihiro; Guillon, Virginia; Schirò, Giorgio; Coquelle, Nicolas; Woodhouse, Joyce; Roux, Laure; Gotthard, Guillaume; Royant, Antoine; Uriarte, Lucas Martinez; Ruckebusch, Cyril; Joti, Yasumasa; Byrdin, Martin; Mizohata, Eiichi; Nango, Eriko; Tanaka, Tomoyuki; Tono, Kensuke; Yabashi, Makina; Adam, Virgile; Cammarata, Marco; Schlichting, Ilme; Bourgeois, Dominique; Weik, Martin

    2016-03-03

    Reversibly photoswitchable fluorescent proteins find growing applications in cell biology, yet mechanistic details, in particular on the ultrafast photochemical time scale, remain unknown. We employed time-resolved pump-probe absorption spectroscopy on the reversibly photoswitchable fluorescent protein IrisFP in solution to study photoswitching from the nonfluorescent (off) to the fluorescent (on) state. Evidence is provided for the existence of several intermediate states on the pico- and microsecond time scales that are attributed to chromophore isomerization and proton transfer, respectively. Kinetic modeling favors a sequential mechanism with the existence of two excited state intermediates with lifetimes of 2 and 15 ps, the second of which controls the photoswitching quantum yield. In order to support that IrisFP is suited for time-resolved experiments aiming at a structural characterization of these ps intermediates, we used serial femtosecond crystallography at an X-ray free electron laser and solved the structure of IrisFP in its on state. Sample consumption was minimized by embedding crystals in mineral grease, in which they remain photoswitchable. Our spectroscopic and structural results pave the way for time-resolved serial femtosecond crystallography aiming at characterizing the structure of ultrafast intermediates in reversibly photoswitchable fluorescent proteins.

  13. 一个基于兴趣度的FP-Growth算法改进%A Improved Algorithm Based on Interest Degree for FP-Growth

    Institute of Scientific and Technical Information of China (English)

    曾安平; 黄永平; 阳万安; 李广军; 唐远翔

    2008-01-01

    人们已经提出了许多用于高效地发现大规模数据库中关联规则的算法,但它们大多会产生大量的关联规则,这些规则中包含很多用户不感兴趣的垃圾规则,且只能发现正项的关联规则.因此,引入兴趣度的概念,对FP-Growth算法进行改造,发现一些用户真正感兴趣的有用关联规则,这些规则允许包含负项规则.

  14. Studying Nuclear Receptor Complexes in the Cellular Environment.

    Science.gov (United States)

    Schaufele, Fred

    2016-01-01

    The ligand-regulated structure and biochemistry of nuclear receptor complexes are commonly determined by in vitro studies of isolated receptors, cofactors, and their fragments. However, in the living cell, the complexes that form are governed not just by the relative affinities of isolated cofactors for the receptor but also by the cell-specific sequestration or concentration of subsets of competing or cooperating cofactors, receptors, and other effectors into distinct subcellular domains and/or their temporary diversion into other cellular activities. Most methods developed to understand nuclear receptor function in the cellular environment involve the direct tagging of the nuclear receptor or its cofactors with fluorescent proteins (FPs) and the tracking of those FP-tagged factors by fluorescence microscopy. One of those approaches, Förster resonance energy transfer (FRET) microscopy, quantifies the transfer of energy from a higher energy "donor" FP to a lower energy "acceptor" FP attached to a single protein or to interacting proteins. The amount of FRET is influenced by the ligand-induced changes in the proximities and orientations of the FPs within the tagged nuclear receptor complexes, which is an indicator of the structure of the complexes, and by the kinetics of the interaction between FP-tagged factors. Here, we provide a guide for parsing information about the structure and biochemistry of nuclear receptor complexes from FRET measurements in living cells.

  15. Regulation of vascular cell adhesion molecule-1 in dental pulp cells by interleukin-1β: the role of prostanoids.

    Science.gov (United States)

    Chang, Mei-Chi; Lin, Li-Deh; Zwei-Ching Chang, Jenny; Huang, Chiung-Fang; Chuang, Fu-Hsiung; Lee, Jang-Jaer; Jeng, Po-Yuan; Wang, Tong-Mei; Jeng, Jiiang-Huei

    2012-06-01

    Vascular cell adhesion molecule (VCAM-1) plays a critical role in the inflammatory processes by stimulating the recruitment, extravasation, and migration of leukocytes. Its expression and regulation in the dental pulp is not well elucidated. Primary dental pulp cells were exposed to prostaglandin E(2) (PGE(2)), prostaglandin F(2α) (PGF(2α)), or interleukin 1β (IL-1β) with/without aspirin. VCAM-1 messenger RNA expression was analyzed by reverse transcriptase-polymerase chain reaction. Soluble VCAM-1 (sVCAM-1) in the culture medium was determined by enzyme-linked immunosorbent assay, and the number of viable cells was estimated by (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. IL-1β induced VCAM-1 gene expression of pulp cells. IL-1β also stimulated sVCAM-1 production. The IL-1β-induced sVCAM-1 production was not inhibited but rather enhanced by aspirin, a cyclooxygenase (COX) inhibitor. PGE(2) and PGF(2α) decreased the VCAM-1 expression and sVCAM-1 production of pulp cells. U0126 (1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene), a mitogen-activated protein kinase kinase (MEK) inhibitor, attenuated IL-1β-induced sVCAM-1 production. However, no marked cytotoxicity was noted in these experimental conditions as analyzed by MTT assay. IL-1β may be involved in the pulpal inflammatory processes via stimulation of VCAM-1 expression and sVCAM-1 production. This event is not mediated by COX activation and prostanoid production but is associated with MEK signaling. PGE(2) and PGF(2α) may potentially regulate inflammatory processes by the inhibition of VCAM-1. Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  16. Monitoring of experimental rat lung transplants by high-resolution flat-panel volumetric computer tomography (fpVCT).

    Science.gov (United States)

    Greschus, Susanne; Kuchenbuch, Tim; Plötz, Christian; Obert, Martin; Traupe, Horst; Padberg, Winfried; Grau, Veronika; Hirschburger, Markus

    2009-01-01

    Noninvasive assessment of experimental lung transplants with high resolution would be favorable to exclude technical failure and to follow up graft outcome in the living animal. Here we describe a flat-panel Volumetric Computed Tomography (fpVCT) technique using a prototype scanner. Lung transplantation was performed in allogeneic as well as in corresponding syngeneic rat strain combinations. At different time points post-transplantation, fpVCT was performed. Lung transplants can be visualized in the living rat with high-spatial resolution. FpVCT allows a detailed analysis of the lung and the bronchi. Infiltrates developing during rejection episodes can be diagnosed and follow-up studies can easily be performed. With fpVCT it is possible to control the technical success of the surgical procedure. Graft rejection can be visualized individually in the living animal noninvasively, which is highly advantageous for studying the pathogenesis of chronic rejection or to monitor new therapies.

  17. Why are infant and child mortality rates lower in the MCH-FP area of Matlab, Bangladesh?

    Science.gov (United States)

    Hale, Lauren; DaVanzo, Julie; Razzaque, Abdur; Rahman, Mizanur

    2006-12-01

    Infant and child mortality rates are significantly lower in the Maternal and Child Health-Family Planning (MCH-FP) area of Matlab, Bangladesh, than in a comparison area. The two areas are similar in terms of socioeconomic characteristics, but the MCH-FP area provides better maternal and child health and family planning services, resulting in different reproductive patterns, including lower fertility rates and longer intervals between pregnancies. We use data from the Matlab Demographic Surveillance System for nearly 126,000 singleton live births that occurred between 1982 and 2002 to investigate the extent to which the different reproductive patterns in the MCH-FP area explain why infant and child mortality rates are lower there. Differences in reproductive patterns account for a small portion (up to 20 percent) of the variation in these rates between the MCH-FP and comparison areas, suggesting that the majority of the difference is due to the quality of MCH services.

  18. Loss of EP2 Receptor Subtype in Colonic Cells Compromise Epithelial Barrier Integrity by Altering Claudin-4

    OpenAIRE

    Manigandan Lejeune; France Moreau; Kris Chadee

    2014-01-01

    Prostaglandin E2 (PGE2) is a bioactive lipid mediator that exerts its biological function through interaction with four different subtypes of E-Prostanoid receptor namely EP1, EP2, EP3 and EP4. It has been known that EP2 receptor is differentially over-expressed in the epithelia of inflamed human colonic mucosa. However, the significance of the differential expression in altering epithelial barrier function is not known. In this study, we used Caco-2 cells expressing EP2 receptor, either high...

  19. trans and cis Chromophore structures in the kindling fluorescent protein asFP595

    Science.gov (United States)

    Grigorenko, Bella; Savitsky, Alexander; Topol, Igor; Burt, Stanley; Nemukhin, Alexander

    2006-06-01

    The ab initio QM/MM calculations are used to optimize geometry configurations of the chromophore and surrounding residues for the kindling protein asFP595. The time-dependent DFT method is applied to estimate parameters of the S 0-S 1 vertical transition of the chromophore at the protein geometry taking into account effects from the nearest residues. The results of simulations provide a theoretical support to the hypothesis on the possibility of trans-cis izomerization of the chromophore in the mechanism of kindling. The system can absorb light in the trans anion form of the chromophore and emit at longer wavelength in the cis anion form.

  20. Time-series photometry of the O4 I(n)fp star zeta Puppis

    OpenAIRE

    Howarth, Ian D.; Stevens, Ian R.

    2014-01-01

    We report a time-series analysis of the O4 I(n)fp star zeta Pup, based on optical photometry obtained with the SMEI instrument on the Coriolis satellite, 2003--2006. A single astrophysical signal is found, with P = (1.780938 \\pm 0.000093) d and a mean semi-amplitude of (6.9 \\pm 0.3) mmag. There is no evidence for persistent coherent signals with semi-amplitudes in excess of ca. 2~mmag on any of the timescales previously reported in the literature. In particular, there is no evidence for a sig...

  1. Manifestations of Isospin in Nearest Neighbor Spacing Distributions for the f-p Model Space

    CERN Document Server

    Quinonez, Michael; Zamick, Larry

    2016-01-01

    The strong interactions are charge independent. If we limit ourselves to the strong interactions, we have the isospin $T$ as a good quantum number. Here we consider the lack of level repulsion of states of different isospin and how this effect manifests in nearest neighbor spacing (NNS) histograms, which provide a visual and statistical context in which to study distributions of energy level spacings. In particular, we study nucleons in the f-p model space for the nucleus $^{44}$Ti. We also study the effect of the Coulomb interaction on the level spacing distribution.

  2. File Specification for GEOS-5 FP-IT (Forward Processing for Instrument Teams)

    Science.gov (United States)

    Lucchesi, R.

    2013-01-01

    The GEOS-5 FP-IT Atmospheric Data Assimilation System (GEOS-5 ADAS) uses an analysis developed jointly with NOAA's National Centers for Environmental Prediction (NCEP), which allows the Global Modeling and Assimilation Office (GMAO) to take advantage of the developments at NCEP and the Joint Center for Satellite Data Assimilation (JCSDA). The GEOS-5 AGCM uses the finite-volume dynamics (Lin, 2004) integrated with various physics packages (e.g, Bacmeister et al., 2006), under the Earth System Modeling Framework (ESMF) including the Catchment Land Surface Model (CLSM) (e.g., Koster et al., 2000). The GSI analysis is a three-dimensional variational (3DVar) analysis applied in grid-point space to facilitate the implementation of anisotropic, inhomogeneous covariances (e.g., Wu et al., 2002; Derber et al., 2003). The GSI implementation for GEOS-5 FP-IT incorporates a set of recursive filters that produce approximately Gaussian smoothing kernels and isotropic correlation functions. The GEOS-5 ADAS is documented in Rienecker et al. (2008). More recent updates to the model are presented in Molod et al. (2011). The GEOS-5 system actively assimilates roughly 2 × 10(exp 6) observations for each analysis, including about 7.5 × 10(exp 5) AIRS radiance data. The input stream is roughly twice this volume, but because of the large volume, the data are thinned commensurate with the analysis grid to reduce the computational burden. Data are also rejected from the analysis through quality control procedures designed to detect, for example, the presence of cloud. To minimize the spurious periodic perturbations of the analysis, GEOS-5 FP-IT uses the Incremental Analysis Update (IAU) technique developed by Bloom et al. (1996). More details of this procedure are given in Appendix A. The analysis is performed at a horizontal resolution of 0.625-degree longitude by 0.5-degree latitude and at 72 levels, extending to 0.01 hPa. All products are generated at the native resolution of the

  3. Computer program system for evaluation of FP nuclear data for JENDL. Smooth part

    Energy Technology Data Exchange (ETDEWEB)

    Nakagawa, Tsuneo [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment; Watanabe, Takashi; Iijima, Shungo

    1997-12-01

    This report describes computer programs used to evaluate nuclear data of fission product (FP) nuclides stored in an evaluated nuclear data library JENDL, especially in the smooth part above the resonance region. Many programs were used for determination of nuclear model parameters, calculation of nuclear data, handling of experimental and/or calculated data, and so on. Among them, reported here are programs for determination of level density parameters (ENSDFRET, LVLPLOT, LEVDES), for making sets of JCL and input data for the theoretical calculation program CASTHY (JOBSETTER, INDES/CASTHY), and for conversion of format of CASTHY output files to the ENDF format (CTOB2). (author). 51 refs.

  4. Naphthalene/quinoline amides and sulfonylureas as potent and selective antagonists of the EP4 receptor.

    Science.gov (United States)

    Burch, Jason D; Farand, Julie; Colucci, John; Sturino, Claudio; Ducharme, Yves; Friesen, Richard W; Lévesque, Jean-François; Gagné, Sébastien; Wrona, Mark; Therien, Alex G; Mathieu, Marie-Claude; Denis, Danielle; Vigneault, Erika; Xu, Daigen; Clark, Patsy; Rowland, Steve; Han, Yongxin

    2011-02-01

    Two new series of EP(4) antagonists based on naphthalene/quinoline scaffolds have been identified as part of our on-going efforts to develop treatments for inflammatory pain. One series contains an acidic sulfonylurea pharmacophore, whereas the other is a neutral amide. Both series show subnanomolar intrinsic binding potency towards the EP(4) receptor, and excellent selectivity towards other prostanoid receptors. While the amide series generally displays poor pharmacokinetic parameters, the sulfonylureas exhibit greatly improved profile. MF-592, the optimal compound from the sulfonylurea series, has a desirable overall preclinical profile that suggests it is suitable for further development.

  5. Platelet receptors and patient responses: The contributions of Professor Stan Heptinstall to platelet research.

    Science.gov (United States)

    Clemetson, Kenneth J

    2015-01-01

    Stan Heptinstall's contributions to platelet research covered organising meetings at the national and European level as well as starting and maintaining the journal "Platelets". The major part of his research addressed problems of inhibition of platelet receptors and the effects of this on patient health. In particular, the effects of P2Y12 inhibitors on patients with acute cardiovascular problems were a major focus. Other studies included the effects of feverfew (Tanacetum parthenium) extracts on platelets, of direct anti-IIb/IIIa receptor (αIIbβ3) inhibitors and of prostanoids on platelet function. Recently, methods for assessing the effectiveness of platelet inhibition were investigated.

  6. Removal of transposon target sites from the Autographa californica multiple nucleopolyhedrovirus fp25k gene delays, but does not prevent, accumulation of the few polyhedra phenotype.

    Science.gov (United States)

    Giri, Lopamudra; Li, Huarang; Sandgren, David; Feiss, Michael G; Roller, Richard; Bonning, Bryony C; Murhammer, David W

    2010-12-01

    Low-cost, large-scale production of the baculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV) using continuous insect cell culture is seriously hindered by the accumulation of AcMNPV mutants. Specifically, few-polyhedra (FP) mutants, with a reduced yield of occluded virus (polyhedra) and decreased infectivity, usually accumulate upon passaging in cell culture. FP mutations result from transposon insertions in the baculovirus fp25k gene, leading to significantly reduced levels of FP25K protein synthesis. This study evaluated the effects of removing the transposon insertion sites from the wild-type baculovirus fp25k gene; the mutated virus was denoted Ac-FPm. Specifically, this study involved a detailed comparison of wild-type (WT) AcMNPV and Ac-FPm with regard to the proportion of cells having polyhedra, number of polyhedra per cell, the fraction of empty polyhedra, number of occlusion-derived viruses per polyhedron, number of nucleocapsids in the nuclei, FP25K protein synthesis and genetic analysis of the fp25k gene. Removal of TTAA transposon insertion sites from the fp25k gene stabilized FP25K protein synthesis and delayed the appearance of the FP phenotype from passage 5 to passage 10. Electron micrographs revealed that more virus particles were found inside the nuclei of cells infected with Ac-FPm than in the nuclei of cells infected with WT AcMNPV (at passage 10). Abnormalities, however, were observed in envelopment of nucleocapsids and virus particle occlusion within Ac-FPm polyhedra. Thus, the FP phenotype appeared in spite of continued FP25K protein synthesis, suggesting that mechanisms other than fp25k gene disruption can lead to the FP phenotype.

  7. Improvements in start system of ETE-RH/FP fans; Melhorias no sistema de partida dos ventiladores da ETE-RH/FP

    Energy Technology Data Exchange (ETDEWEB)

    Martinez, Flavio Costa; Sinzato, Frederico Takashi Di Tanno; Assis, Marcio Souza de [ArcelorMittal Tubarao, ES (Brazil). Dept. de Producao de Gusa e Energia

    2009-11-01

    The present technical contribution presents the results achieved with the improvement of start control of Effluent Treatment Station of RH furnace and Ladle furnace (ETE-RH/FP) fans. This work started from the necessity to find a solution to decrease the constant mechanical breaks of fans on the station, where it has been used two fans per cell in the tower, which means that when one is working, the other in the same cell is turned off. The second fan turns the other way round, and when the same is turned on it causes a 'bang' strong enough to break its elements, such as braces and gears. With the use of soft start, the same, besides to start the motor of the fan in a soft way, still does that the fan stop turning the other way round before the start, preventing the 'bangs' in the equipment. Another important item considered in the solution was the harmonic generation. The soft start generate few harmonic, if compared to a frequency inverter. The introduction of this new start system of fans of station, besides the reduction of costs of the repair maintenance, brought an important electrical energy saving, being aligned with the new projects of the company. (author)

  8. Castor oil induces laxation and uterus contraction via ricinoleic acid activating prostaglandin EP3 receptors.

    Science.gov (United States)

    Tunaru, Sorin; Althoff, Till F; Nüsing, Rolf M; Diener, Martin; Offermanns, Stefan

    2012-06-01

    Castor oil is one of the oldest drugs. When given orally, it has a laxative effect and induces labor in pregnant females. The effects of castor oil are mediated by ricinoleic acid, a hydroxylated fatty acid released from castor oil by intestinal lipases. Despite the wide-spread use of castor oil in conventional and folk medicine, the molecular mechanism by which ricinoleic acid acts remains unknown. Here we show that the EP(3) prostanoid receptor is specifically activated by ricinoleic acid and that it mediates the pharmacological effects of castor oil. In mice lacking EP(3) receptors, the laxative effect and the uterus contraction induced via ricinoleic acid are absent. Although a conditional deletion of the EP(3) receptor gene in intestinal epithelial cells did not affect castor oil-induced diarrhea, mice lacking EP(3) receptors only in smooth-muscle cells were unresponsive to this drug. Thus, the castor oil metabolite ricinoleic acid activates intestinal and uterine smooth-muscle cells via EP(3) prostanoid receptors. These findings identify the cellular and molecular mechanism underlying the pharmacological effects of castor oil and indicate a role of the EP(3) receptor as a target to induce laxative effects.

  9. Global properties of fp-shell interactions in many-nucleon systems

    Energy Technology Data Exchange (ETDEWEB)

    Sviratcheva, K.D. [Department of Physics and Astronomy, Louisiana State University, Baton Rouge, Louisiana 70803 (United States)]. E-mail: kristina@baton.phys.lsu.edu; Draayer, J.P. [Department of Physics and Astronomy, Louisiana State University, Baton Rouge, Louisiana 70803 (United States); Vary, J.P. [Department of Physics and Astronomy, Iowa State University, Ames, IA 50011 (United States); Lawrence Livermore National Laboratory, Livermore, California 94551, Stanford Linear Accelerator Center, Stanford University, Stanford, CA 94309 (United States)

    2007-04-15

    Spectral distribution theory, which can be used to compare microscopic interactions over a broad range of nuclei, is applied in an analysis of two modern effective interactions based on the realistic CD-Bonn potential for 0{omega} no-core shell model calculations in the fp shell, as well as in a comparison of these with the realistic shell-model GXPF1 interaction. In particular, we explore the ability of these interaction to account for the development of isovector pairing correlations and collective rotational motion in the fp shell. Our findings expose the similarities of these two-body interactions, especially as this relates to their pairing and rotational characteristics. Further, the GXPF1 interaction is used to determine the strength parameter of a quadrupole term that can be used to augment an isovector-pairing model interaction with Sp(4) dynamical symmetry, which in turn is shown to yield reasonable agreement with the low-lying energy spectra of {sup 58}Ni and {sup 58}Cu.

  10. A Human "eFP" Browser for Generating Gene Expression Anatograms.

    Directory of Open Access Journals (Sweden)

    Rohan V Patel

    Full Text Available Transcriptomic studies help to further our understanding of gene function. Human transcriptomic studies tend to focus on a particular subset of tissue types or a particular disease state; however, it is possible to collate into a compendium multiple studies that have been profiled using the same expression analysis platform to provide an overview of gene expression levels in many different tissues or under different conditions. In order to increase the knowledge and understanding we gain from such studies, intuitive visualization of gene expression data in such a compendium can be useful. The Human eFP ("electronic Fluorescent Pictograph" Browser presented here is a tool for intuitive visualization of large human gene expression data sets on pictographic representations of the human body as gene expression "anatograms". Pictographic representations for new data sets may be generated easily. The Human eFP Browser can also serve as a portal to other gene-specific information through link-outs to various online resources.

  11. A Magnetic Field Sensor Based on a Magnetic Fluid-Filled FP-FBG Structure

    Directory of Open Access Journals (Sweden)

    Ji Xia

    2016-04-01

    Full Text Available Based on the characteristic magnetic-controlled refractive index property, in this paper, a magnetic fluid is used as a sensitive medium to detect the magnetic field in the fiber optic Fabry-Perot (FP cavity. The temperature compensation in fiber Fabry-Perot magnetic sensor is demonstrated and achieved. The refractive index of the magnetic fluid varies with the applied magnetic field and external temperature, and a cross-sensitivity effect of the temperature and magnetic field occurs in the Fabry-Perot magnetic sensor and the accuracy of magnetic field measurements is affected by the thermal effect. In order to overcome this problem, we propose a modified sensor structure. With a fiber Bragg grating (FBG written in the insert fiber end of the Fabry-Perot cavity, the FBG acts as a temperature compensation unit for the magnetic field measurement and it provides an effective solution to the cross-sensitivity effect. The experimental results show that the sensitivity of magnetic field detection improves from 0.23 nm/mT to 0.53 nm/mT, and the magnetic field measurement resolution finally reaches 37.7 T. The temperature-compensated FP-FBG magnetic sensor has obvious advantages of small volume and high sensitivity, and it has a good prospect in applications in the power industry and national defense technology areas.

  12. [Quantitative evaluation of 123I-FP-CIT SPECT: validation of a semiautomated method].

    Science.gov (United States)

    Lorenzo Bosquet, C; Cuberas Borrós, G; Miquel Rodríguez, F; Caresia, P; Aguadé Bruix, S; Castell Conesa, J

    2005-01-01

    To assess the utility of a quantification of the 123I-FP-CIT uptake by the definition of some reference values, normal range values and interobserver variation. Fifty patients with a 123I-FP-CIT SPECT: 25 patients had a pathological SPECT with the diagnosis of Parkinson's disease and the remaining had a qualitative normal SPET, with the diagnosis of 14 drug-induced Parkinsonism and 11 with psychogenic Parkinsonism. In the transversal slices, the best central slice that showed the nuclei of the base best was selected and standard ROIs (Region Of Interest) were applied. Specific (caudate and putamen) versus non specific (occipital) and laterality ratios were calculated. A normal statistical analysis for independent quantitative samples was used (mean, standard deviation and range) as well as variation coefficient and correlation coefficient of two observers and the 10th and 90th percentile. The variation coefficient interobserver was 3.24-5.61 and the correlation coefficient was 0.89-0.99. Cut-off values between both populations were established at 2.10 in the right putamen and at 2.05 in the left. Cut-off values definition in caudate were not assessable due to overlapping of ratios of both populations. This quantification method is highly reproducible. It makes it possible to obtain reference values and to define normal range.

  13. Modeling trans-cis chromophore isomerization for the asFP595 kindling protein

    Science.gov (United States)

    Grigorenko, Bella L.; Nemukhin, Alexander V.

    2007-02-01

    We present the results of modeling properties of the chromophore, 2-acetyl-4-(p-hydroxybenzylidene)-1-methyl-5- imidazolone (AHBMI), from the newly discovered fluorescent protein asFP595 inside the protein environment by using the combined quantum mechanical - molecular mechanical (QM/MM) method. In this approach, the chromophore unit and the side chains of the nearest amino acid residues are assigned to the quantum subsystem. The starting coordinates of heavy atoms were taken from the relevant crystal structures of the protein. Hydrogen atoms were added manually, and the structure of the model protein system was optimized by using QM/MM energy minimization for the trans-form of the chromophore. The Hartree-Fock/6-31G quantum chemical approximation and the AMBER force field parameters were employed in geometry optimization. The points on potential energy surfaces of the ground and first and second excited electronic states were computed with the complete active space self-consistent field approximation in the quantum subsystem under different choices of the QM/MM partitioning. Possible pathways for the trans-cis photo isomerization presumably responsible for the kindling properties of asFP595 as well as other mechanisms of photo excitation are discussed.

  14. Hybrid wireless-over-fiber transmission system based on multiple injection-locked FP LDs.

    Science.gov (United States)

    Li, Chung-Yi; Lu, Hai-Han; Chu, Chien-An; Ying, Cheng-Ling; Lu, Ting-Chien; Peng, Peng-Chun

    2015-07-27

    A hybrid wireless-over-fiber (WoF) transmission system based on multiple injection-locked Fabry-Perot laser diodes (FP LDs) is proposed and experimentally demonstrated. Unlike the traditional hybrid WoF transmission systems that require multiple distributed feedback (DFB) LDs to support different kinds of services, the proposed system employs multiple injection-locked FP LDs to provide different kinds of applications. Such a hybrid WoF transmission system delivers downstream intensity-modulated 20-GHz microwave (MW)/60-GHz millimeter-wave (MMW)/550-MHz cable television (CATV) signals and upstream phase-remodulated 20-GHz MW signal. Excellent bit error rate (BER), carrier-to-noise ratio (CNR), composite second-order (CSO), and composite triple-beat (CTB) are observed over a 40-km single-mode fiber (SMF) and a 4-m radio frequency (RF) wireless transport. Such a hybrid WoF transmission system has practical applications for fiber-wireless convergence to provide broadband integrated services, including telecommunication, data communication, and CATV services.

  15. A Magnetic Field Sensor Based on a Magnetic Fluid-Filled FP-FBG Structure.

    Science.gov (United States)

    Xia, Ji; Wang, Fuyin; Luo, Hong; Wang, Qi; Xiong, Shuidong

    2016-04-29

    Based on the characteristic magnetic-controlled refractive index property, in this paper, a magnetic fluid is used as a sensitive medium to detect the magnetic field in the fiber optic Fabry-Perot (FP) cavity. The temperature compensation in fiber Fabry-Perot magnetic sensor is demonstrated and achieved. The refractive index of the magnetic fluid varies with the applied magnetic field and external temperature, and a cross-sensitivity effect of the temperature and magnetic field occurs in the Fabry-Perot magnetic sensor and the accuracy of magnetic field measurements is affected by the thermal effect. In order to overcome this problem, we propose a modified sensor structure. With a fiber Bragg grating (FBG) written in the insert fiber end of the Fabry-Perot cavity, the FBG acts as a temperature compensation unit for the magnetic field measurement and it provides an effective solution to the cross-sensitivity effect. The experimental results show that the sensitivity of magnetic field detection improves from 0.23 nm/mT to 0.53 nm/mT, and the magnetic field measurement resolution finally reaches 37.7 T. The temperature-compensated FP-FBG magnetic sensor has obvious advantages of small volume and high sensitivity, and it has a good prospect in applications in the power industry and national defense technology areas.

  16. Space weather in the EU’s FP7 Space Theme

    Directory of Open Access Journals (Sweden)

    Chiarini Paola

    2013-11-01

    Full Text Available Technological infrastructures in space and on ground provide services on which modern society and economies rely. Space weather related research is funded under the 7th Framework Programme for Research and Innovation (FP7 of the European Union in response to the need of protecting such critical infrastructures from the damage which could be caused by extreme space weather events. The calls for proposals published under the topic “Security of space assets from space weather events” of the FP7 Space Theme aimed to improve forecasts and predictions of disruptive space weather events as well as identify best practices to limit the impacts on space- and ground-based infrastructures and their data provision. Space weather related work was also funded under the topic “Exploitation of space science and exploration data”, which aims to add value to space missions and Earth-based observations by contributing to the effective scientific exploitation of collected data. Since 2007 a total of 20 collaborative projects have been funded, covering a variety of physical phenomena associated with space weather, from ionospheric disturbances and scintillation, to geomagnetically induced currents at Earth’s surface, to coronal mass ejections and solar energetic particles. This article provides an overview of the funded projects, touching upon some results and referring to specific websites for a more exhaustive description of the projects’ outcomes.

  17. Production of baculovirus defective interfering particles during serial passage is delayed by removing transposon target sites in fp25k.

    Science.gov (United States)

    Giri, Lopamudra; Feiss, Michael G; Bonning, Bryony C; Murhammer, David W

    2012-02-01

    Accumulation of baculovirus defective interfering particle (DIP) and few polyhedra (FP) mutants is a major limitation to continuous large-scale baculovirus production in insect-cell culture. Although overcoming these mutations would result in a cheaper platform for producing baculovirus biopesticides, little is known regarding the mechanism of FP and DIP formation. This issue was addressed by comparing DIP production of wild-type (WT) Autographa californica multiple nucleopolyhedrovirus (AcMNPV) with that of a recombinant AcMNPV (denoted Ac-FPm) containing a modified fp25k gene with altered transposon insertion sites that prevented transposon-mediated production of the FP phenotype. In addition to a reduction in the incidence of the FP phenotype, DIP formation was delayed on passaging of Ac-FPm compared with WT AcMNPV. Specifically, the yield of DIP DNA in Ac-FPm was significantly lower than in WT AcMNPV up to passage 16, thereby demonstrating that modifying the transposon insertion sites increases the genomic stability of AcMNPV. A critical component of this investigation was the optimization of a systematic method based on the use of pulsed-field gel electrophoresis (PFGE) to characterize extracellular virus DNA. Specifically, PFGE was used to detect defective genomes, determine defective genome sizes and quantify the amount of defective genome within a heterogeneous genome population of passaged virus.

  18. PGE2 Modulates GABAA Receptors via an EP1 Receptor-Mediated Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Guang Yang

    2015-07-01

    Full Text Available Aims: PGE2 is one of the most abundant prostanoids in mammalian tissues, but its effect on neuronal receptors has not been well investigated. This study examines the effect of PGE2 on GABAA receptor currents in rat cerebellar granule neurons. Methods: GABAA currents were recorded using a patch-clamp technique. Cell surface and total protein of GABAA β1/2/3 subunits was carried out by Western blot analysis. Results: Upon incubation of neurons with PGE2 (1 µM for 60 minutes, GABAA currents were significantly potentiated. This PGE2-driven effect could be blocked by PKC or CaMKII inhibitors as well as EP1 receptor antagonist, and mimicked by PMA or EP1 receptor agonist. Furthermore, Western blot data showed that PGE2 did not increase the total expression level of GABAA receptors, but significantly increased surface levels of GABAA β1/2/3 subunits after 1 h of treatment. Consistently, both PKC and CaMKII inhibitors were able to reduce PGE2-induced increases in cell surface expression of GABAA receptors. Conclusion: Activation of either the PKC or CaMKII pathways by EP1 receptors mediates the PGE2-induced increase in GABAA currents. This suggests that upregulation of postsynaptic GABAA receptors by PGE2 may have profound effects on cerebellar functioning under physiological and pathological conditions.

  19. Detection of thiopurine s-methyltransferase mutations by template directed determinator in incorporation with fluorescence polarization(TDI-FP)

    Institute of Scientific and Technical Information of China (English)

    白玉杰; 赵锦荣; 张文红; 薛丽; 郭晏海; 闫小君

    2003-01-01

    Objective:To develop a new method for the detection of TPMT gene mutations and determine thefrequencies of four TPM alleles,TPMT*1,*3A,*3B and *3C in a healthy Chinese population.Methods:A TDI-FP assay system was set up in out lab.To evaluate this system,220 healthy individuals were analyzed for the polymorphisites at positions 460(G→A)and 719(A→G)of the TPMP gene using our new TDI-FP method.Results:Three TPMP*3C(G460→G719)heterozygotes were identified,TPMP *3A and TPMP *3B were not found.All mutations were confirmed by conventional DNA sequencing analysis.Conclusion:TDI-FP method has proven to be very efficient as a rapid and accurate approach for TPMP genotyping.TPMP *3C was the only polymorphism identified in this clinical samples we have registered.

  20. Safety and immunogenicity of the malaria candidate vaccines FP9 CS and MVA CS in adult Gambian men.

    Science.gov (United States)

    Imoukhuede, E B; Berthoud, T; Milligan, P; Bojang, K; Ismaili, J; Keating, S; Nwakanma, D; Keita, S; Njie, F; Sowe, M; Todryk, S; Laidlaw, S M; Skinner, M A; Lang, T; Gilbert, S; Greenwood, B M; Hill, A V S

    2006-10-30

    We assessed the safety and immunogenicity of prime-boost vectors encoding the Plasmodium falciparum circumsporozoite (CS) protein expressed either in the attenuated fowl-pox virus (FP9) or modified vaccinia virus Ankara (MVA). Thirty-two adult Gambians in groups of four to eight received one, two or three doses of FP9 CS and/or MVA CS. No serious adverse event was observed following vaccination. The most immunogenic regimen was two doses of FP9 followed by a single dose of MVA 4 weeks later (an average of 1000 IFN-gamma spot forming units/million PBMCs). This level of effector T-cell responses appears higher than that seen in previously reported studies of CS-based candidate malaria vaccines.

  1. LanFP10-A, first functional fluorescent protein whose chromophore contains the elusive mutation G67A.

    Science.gov (United States)

    Roldán-Salgado, Abigail; Sánchez-Barreto, Celidee; Gaytán, Paul

    2016-11-01

    Since Green Fluorescent Protein (GFP) was first successfully expressed in heterologous systems in 1994, many genes encoding other natural autofluorescent proteins (AFPs) have been cloned and subsequently modified by protein engineering to improve their physicochemical properties. Throughout this twenty-two-year period, glycine 67 (Gly67) has been regarded as the only amino acid in the entire protein family that is essential for the formation of the different reported chromophores. In this work, we demonstrate that a synthetic gene encoding LanFP10-A, a natural protein encoded in the genome of the lancelet Branchiostoma floridae containing the G67A mutation, produces a heterologous, functional yellow fluorescent protein when expressed in E. coli. In contrast to LanFP10-A, LanFP6-A, a second GFP-like protein found in the lancelet genome that also contains the natural G67A mutation, was non-fluorescent.

  2. SACSESS – the EURATOM FP7 project on actinide separation from spent nuclear fuels

    Directory of Open Access Journals (Sweden)

    Bourg Stéphane

    2015-12-01

    Full Text Available Recycling of actinides by their separation from spent nuclear fuel, followed by transmutation in fast neutron reactors of Generation IV, is considered the most promising strategy for nuclear waste management. Closing the fuel cycle and burning long-lived actinides allows optimizing the use of natural resources and minimizing the long-term hazard of high-level nuclear waste. Moreover, improving the safety and sustainability of nuclear power worldwide. This paper presents the activities striving to meet these challenges, carried out under the Euratom FP7 collaborative project SACSESS (Safety of Actinide Separation Processes. Emphasis is put on the safety issues of fuel reprocessing and waste storage. Two types of actinide separation processes, hydrometallurgical and pyrometallurgical, are considered, as well as related aspects of material studies, process modeling and the radiolytic stability of solvent extraction systems. Education and training of young researchers in nuclear chemistry is of particular importance for further development of this field.

  3. Nuclear β --decay half-lives for {fp} and {fpg} shell nuclei

    Science.gov (United States)

    Kumar, Vikas; Srivastava, P. C.; Li, Hantao

    2016-10-01

    In the present work we calculate the allowed {β }--decay half-lives of nuclei with Z=20-30 and N ≤slant 50 systematically under the framework of the nuclear shell model. A recent study shows that some nuclei in this region belong to the island of inversion. We perform calculation for fp shell nuclei using the KB3G effective interaction. In the case of Ni, Cu, and Zn, we used the JUN45 effective interaction. Theoretical results of Q values, half-lives, excitation energies, logft values, and branching fractions are discussed and compared with the experimental data. In the Ni region, we also compared our calculated results with recent experimental data (Xu et al 2014 Phys. Rev. Lett. 113 032505). The present results agree with the experimental data of half-lives in comparison to QRPA.

  4. 2nd FP7 Conference and International Summer School Nanotechnology : From Fundamental Research to Innovations

    CERN Document Server

    Yatsenko, Leonid

    2015-01-01

    This book presents some of the latest achievements in nanotechnology and nanomaterials from leading researchers in Ukraine, Europe, and beyond. It features contributions from participants in the 2nd International Summer School “Nanotechnology: From Fundamental Research to Innovations” and International Research and Practice Conference “Nanotechnology and Nanomaterials”, NANO-2013, which were held in Bukovel, Ukraine on August 25-September 1, 2013. These events took place within the framework of the European Commission FP7 project Nanotwinning, and were organized jointly by the Institute of Physics of the National Academy of Sciences of Ukraine, University of Tartu (Estonia), University of Turin (Italy), and Pierre and Marie Curie University (France). Internationally recognized experts from a wide range of universities and research institutions share their knowledge and key results on topics ranging from nanooptics, nanoplasmonics, and interface studies to energy storage and biomedical applications. Pr...

  5. Selected proceedings of the FP7 International Summer School Nanotechnology: From Fundamental Research to Innovations

    CERN Document Server

    Yatsenko, Leonid; Brodin, Mikhaylo; Nanomaterials imaging techniques, surface studies, and applications

    2013-01-01

    This book presents cutting-edge research on a wide range of nanotechnology techniques and applications.  It features contributions from scientists who participated in the International Summer School “Nanotechnology: From Fundamental Research to Innovations” in Bukovel, Ukraine on August 26 – September 2, 2012 funded by the European Commission FP7 project Nanotwinning implemented by the Institute of Physics of National Academy of Sciences of Ukraine and partner institutions: University of Tartu (Estonia), European Profiles A.E. (Greece), University of Turin (Italy) and Université Pierre et Marie Curie (France).  Worldwide experts present the latest results on such key topics as microscopy of nanostructures; nanocomposites; nanostructured interfaces and surfaces; nanooptics; nanoplasmonics; and enhanced vibrational spectroscopy.  Imaging technique coverage ranges from atomic force microscopy and spectroscopy, multiphoton imagery, and laser diagnostics of nanomaterials and nanostructures, to resonance ...

  6. Study on Commercial Application of FP-DSN Sulfur Transfer Additive in FCC Unit

    Institute of Scientific and Technical Information of China (English)

    Gao Siming; Han Rongxian; Chen Desheng

    2009-01-01

    The FCC unit with addition of various inventories of the FP-DSN type sulfur transfer additive was tested in a commercial scale. The effect of the sulfur transfer additive was analyzed by investigating the indicators related with the regenerator flue gas composition, the dry gas composition before desulfurization, the LPG composition before desulfurization, the acid gas, and the yield of gasoline and diesel. The test results indicated that the sulfur was trans-ferred fi'om the feed stream into the dry gas, LPG and acid gas, and the sulfur transfer effect was obvious only when the inventory of sulfur transfer additive exceeded over 2.0% of total FCC catalyst inventory.

  7. Spectroscopy of the odd-odd fp-shell nucleus 52Sc from secondary fragmentation

    CERN Document Server

    Gade, A; Brown, B A; Campbell, C M; Carpenter, M P; Cook, J M; Deacon, A N; Dinca, D C; Freeman, S J; Glasmacher, T; Janssens, R V F; Kay, B P; Mantica, P F; Müller, W F; Terry, J R; Zhu, S

    2006-01-01

    The odd-odd fp-shell nucleus 52Sc was investigated using in-beam gamma-ray spectroscopy following secondary fragmentation of a 55V and 57Cr cocktail beam. Aside from the known gamma-ray transition at 674(5)keV, a new decay at E_gamma=212(3) keV was observed. It is attributed to the depopulation of a low-lying excited level. This new state is discussed in the framework of shell-model calculations with the GXPF1, GXPF1A, and KB3G effective interactions. These calculations are found to be fairly robust for the low-lying level scheme of 52Sc irrespective of the choice of the effective interaction. In addition, the frequency of spin values predicted by the shell model is successfully modeled by a spin distribution formulated in a statistical approach with an empirical, energy-independent spin-cutoff parameter.

  8. 基于磁盘表存储FP-TREE的关联规则挖掘算法%Mining Algorithm of Association Rules Based on Disk Table Resident FP-TREE

    Institute of Scientific and Technical Information of China (English)

    申彦; 宋顺林; 朱玉全

    2012-01-01

    随着现实待挖掘数据库规模不断增长,系统可使用的内存成为用FP-GROWTH算法进行关联规则挖掘的瓶颈.为了摆脱内存的束缚,对大规模数据库中的数据进行关联规则挖掘,基于磁盘的关联规则挖掘成为重要的研究方向.对此,改进原始的FP-TREE数据结构,提出了一种新颖的基于磁盘表的DTRFP-GROWTH (disk table resident FP-TREE growth)算法.该算法利用磁盘表存储FPTREE,降低内存使用,在传统FP-GROWTH算法占用过多内存、挖掘工作无法进行时,以独特的磁盘表存储FP-TREE技术,减少内存使用,能够继续完成挖掘工作,适合空间性能优先的场合.不仅如此,该算法还将关联规则挖掘和关系型数据库整合,克服了基于文件系统相关算法效率较低、开发难度较大等问题.在真实数据集上进行了验证实验以及性能分析.实验结果表明,在内存空间有限的情况下,DTRFP-GROWTH算法是一种有效的基于磁盘的关联规则挖掘算法.%As the size of the database to be mined is increasing constantly, the size of physical memory available has become a bottleneck when using FP-GROWTH algorithm for association rules mining. So. it is necessary to tackle space scalability by some new algorithms in order to mine association rules in huge database. Nowadays, disk-resident algorithm has become the main target. Therefore, the original data structure of FP-TREE is improved and a novel algorithm called DTRFP-GROWTH (disk table resident FP-TREE growth) is presented. This algorithm uses disk table for storing FP-TREE to decrease memory usage. When the mining works failed for FP-GROWTH using too much memory, DTRFP GROWTH can continue to mine association rules from huge database by its special skill called disk table resident FP-TREE, which is suitable to occasions of space performance priority. In addition, this algorithm also integrates association rules mining with RDBMS system. It overcomes the problems of

  9. Marine prostanoids - a review

    Digital Repository Service at National Institute of Oceanography (India)

    Wahidullah, S.; DeSouza, L.

    The occurrence and structure of prostaglandins including clavulones, punaglandins and claviridenones in marine organisms is reviewEd. by comparison of the spectral data reported the identity of 20-acetoxy claviridenones b and c with 20 acetoxy...

  10. Characteristic analysis of a novel F-P interferometer based on a pair of FBGs with built-in LPFGs

    Institute of Scientific and Technical Information of China (English)

    WANG Chun-bao; ZHANG Wei-gang; RUAN Juan; SHANG Jia-bin; YAN Ai-dong

    2012-01-01

    The transmission characteristics of a Fabry-Pérot (F-P) interferometer based on a fiber Bragg grating (FBG) pair with a built-in long-period fiber grating (LPFG) are theoretically analyzed,and the shift of transmission interference fringe as a function of environmental refractive index is acquired.The influence of the lengths of F-P cavity,LPFG and FBG on the transmission characteristics of the proposed interferometer has been numerically investigated,and the simulation results indicate that the sensitivity of refractive index reaches 2.27 × 10-6 for an optical spectrum analyzer (OSA) with a resolution of 1 pm.

  11. EP3 receptors mediate PGE2-induced hypothalamic paraventricular nucleus excitation and sympathetic activation

    Science.gov (United States)

    Zhang, Zhi-Hua; Yu, Yang; Wei, Shun-Guang; Nakamura, Yoshiko; Nakamura, Kazuhiro

    2011-01-01

    Prostaglandin E2 (PGE2), an important mediator of the inflammatory response, acts centrally to elicit sympathetic excitation. PGE2 acts on at least four E-class prostanoid (EP) receptors known as EP1, EP2, EP3, and EP4. Since PGE2 production within the brain is ubiquitous, the different functions of PGE2 depend on the expression of these prostanoid receptors in specific brain areas. The type(s) and location(s) of the EP receptors that mediate sympathetic responses to central PGE2 remain unknown. We examined this question using PGE2, the relatively selective EP receptor agonists misoprostol and sulprostone, and the available selective antagonists for EP1, EP3, and EP4. In urethane-anesthetized rats, intracerebroventricular (ICV) administration of PGE2, sulprostone or misoprostol increased renal sympathetic nerve activity, blood pressure, and heart rate. These responses were significantly reduced by ICV pretreatment with the EP3 receptor antagonist; the EP1 and EP4 receptor antagonists had little or no effect. ICV PGE2 or misoprostol increased the discharge of neurons in the hypothalamic paraventricular nucleus (PVN). ICV misoprostol increased the c-Fos immunoreactivity of PVN neurons, an effect that was substantially reduced by the EP3 receptor antagonist. Real-time PCR detected EP3 receptor mRNA in PVN, and immunohistochemical studies revealed sparsely distributed EP3 receptors localized in GABAergic terminals and on a few PVN neurons. Direct bilateral PVN microinjections of PGE2 or sulprostone elicited sympathoexcitatory responses that were significantly reduced by the EP3 receptor antagonist. These data suggest that EP3 receptors mediate the central excitatory effects of PGE2 on PVN neurons and sympathetic discharge. PMID:21803943

  12. The Receptors that Mediate the Direct Lethality of Anthrax Toxin

    Directory of Open Access Journals (Sweden)

    Stephen H. Leppla

    2012-12-01

    Full Text Available Tumor endothelium marker-8 (TEM8 and capillary morphogenesis protein-2 (CMG2 are the two well-characterized anthrax toxin receptors, each containing a von Willebrand factor A (vWA domain responsible for anthrax protective antigen (PA binding. Recently, a cell-based analysis was used to implicate another vWA domain-containing protein, integrin β1 as a third anthrax toxin receptor. To explore whether proteins other than TEM8 and CMG2 function as anthrax toxin receptors in vivo, we challenged mice lacking TEM8 and/or CMG2. Specifically, we used as an effector protein the fusion protein FP59, a fusion between the PA-binding domain of anthrax lethal factor (LF and the catalytic domain of Pseudomonas aeruginosa exotoxin A. FP59 is at least 50-fold more potent than LF in the presence of PA, with 2 μg PA + 2 μg FP59 being sufficient to kill a mouse. While TEM8−/− and wild type control mice succumbed to a 5 μg PA + 5 μg FP59 challenge, CMG2−/− mice were completely resistant to this dose, confirming that CMG2 is the major anthrax toxin receptor in vivo. To detect whether any toxic effects are mediated by TEM8 or other putative receptors such as integrin β1, CMG2−/−/TEM8−/− mice were challenged with as many as five doses of 50 μg PA + 50 μg FP59. Strikingly, the CMG2−/−/TEM8−/− mice were completely resistant to the 5-dose challenge. These results strongly suggest that TEM8 is the only minor anthrax toxin receptor mediating direct lethality in vivo and that other proteins implicated as receptors do not play this role.

  13. Genetic deletion of aquaporin-1 results in microcardia and low blood pressure in mouse with intact nitric oxide-dependent relaxation, but enhanced prostanoids-dependent relaxation.

    Science.gov (United States)

    Montiel, V; Leon Gomez, E; Bouzin, C; Esfahani, H; Romero Perez, M; Lobysheva, I; Devuyst, O; Dessy, C; Balligand, J L

    2014-02-01

    The water channels, aquaporins (AQPs) are key mediators of transcellular fluid transport. However, their expression and role in cardiac tissue is poorly characterized. Particularly, AQP1 was suggested to transport other molecules (nitric oxide (NO), hydrogen peroxide (H2O2)) with potential major bearing on cardiovascular physiology. We therefore examined the expression of all AQPs and the phenotype of AQP1 knockout mice (vs. wild-type littermates) under implanted telemetry in vivo, as well as endothelium-dependent relaxation in isolated aortas and resistance vessels ex vivo. Four aquaporins were expressed in wild-type heart tissue (AQP1, AQP7, AQP4, AQP8) and two aquaporins in aortic and mesenteric vessels (AQP1-AQP7). AQP1 was expressed in endothelial as well as cardiac and vascular muscle cells and co-segregated with caveolin-1. AQP1 knockout (KO) mice exhibited a prominent microcardia and decreased myocyte transverse dimensions despite no change in capillary density. Both male and female AQP1 KO mice had lower mean BP, which was not attributable to altered water balance or autonomic dysfunction (from baroreflex and frequency analysis of BP and HR variability). NO-dependent BP variability was unperturbed. Accordingly, endothelium-derived hyperpolarizing factor (EDH(F)) or NO-dependent relaxation were unchanged in aorta or resistance vessels ex vivo. However, AQP1 KO mesenteric vessels exhibited an increase in endothelial prostanoids-dependent relaxation, together with increased expression of COX-2. This enhanced relaxation was abrogated by COX inhibition. We conclude that AQP1 does not regulate the endothelial EDH or NO-dependent relaxation ex vivo or in vivo, but its deletion decreases baseline BP together with increased prostanoids-dependent relaxation in resistance vessels. Strikingly, this was associated with microcardia, unrelated to perturbed angiogenesis. This may raise interest for new inhibitors of AQP1 and their use to treat hypertrophic cardiac

  14. FP-PSO算法在认知无线电频谱分配上的应用研究%The application research on cognitive radio spectrum allocation based FP-PSO algorithm

    Institute of Scientific and Technical Information of China (English)

    刘俊霞; 卞琛

    2016-01-01

    针对认知无线电频谱分配时分配率低、用户满意度不高的问题,提出了适应值预测的粒子群优化算法(FPPSO),利用FP-PSO 算法优化了认知无线电频谱分配过程,设计的适应值预测方法提高了分配效率的同时满足了实时性要求。实验结果表明:FP-PSO 算法在降低部分网络效益的同时,获得了比颜色敏感图着色算法(CSGC)更优的用户满意度、平均分配时间和用户公平性。%As distribution rate and customer satisfaction were not high in the process of the spectrum allocation for cognitive radio, Fitness Prediction of Particle Swarm Optimization (FP-PSO) was proposed , using FP-PSO algorithm to optimize the cognitive radio spectrum allocation process , fitness prediction methods is designed to improve the allocation efficiency while meeting the real-time requirements. The experimental results showed that: FP-PSO algorithm reduced a part of network bandwidth benefit, at the same user satisfaction, allocation efficiency, the average assignment time and the user fairness are better than the color sensitive graph coloring algorithm (CSGC).

  15. 基于有序FP-tree的最大长度频繁项集挖掘算法%Algorithm for mining maximal length frequent itemsets based on order FP-tree

    Institute of Scientific and Technical Information of China (English)

    廖福蓉; 王成良

    2012-01-01

    频繁项集的挖掘受到大量候选频繁项集和较高计算花费的限制,只挖掘最大长度频繁项集已满足很多应用.提出一种基于有序FP-tree结构挖掘最大长度频繁项集的算法.即对有序FP-tree的头表进行改造,增加一个max-level域,记录该项在有序FP-tree中的最大高度.挖掘时仅对max-level大于等于已有最大长度频繁项集长度的项进行遍历,不产生条件模式基,无需递归构造条件FP-tree,且计算出最大长度频繁项集的支持度.实验结果表明该算法挖掘效率高、速度快.%The mining of frequent itemsets has been limited by the large number of resulting itemsets as well as the high computational cost. In many application domains, however, it is often sufficient to mine maximum length frequent itemsets. An order FP-tree-based algorithm is proposed for the mining problem. A field max-level is added in head-table to record the greatest height of item. In the mining process, only the item which max-level value is equal or greater than the length of existing maximum length frequent itemsets is traversed. Neither producing conditional pattern base nor constructing conditional frequent pattern tree recursively is needed, and the support of maximum length frequent itemsets is calculated. The experimental results show that the algorithm accelerates the speed to traverse the tree and improves the mining efficiency.

  16. Recommendations for the spatial assessment of air quality resulting from the FP6 EU project Air4EU

    NARCIS (Netherlands)

    Denby, B.; Larssen, S.; Builtjes, P.; Keuken, M.; Sokhi, R.; Moussiopoulos, N.; Douros, J.; Borrego, C.; Costa, A.M.; Pregger, T.

    2011-01-01

    Air4EU is an FP6 European project with the major aim of providing recommendations on methodologies for the spatial assessment of air quality on local, urban and regional scales. The emphasis is on methodologies that combine monitoring and modelling and on spatial assessment for regulatory purposes,

  17. Calibration of gamma camera systems for a multicentre European ¹²³I-FP-CIT SPECT normal database

    DEFF Research Database (Denmark)

    Tossici-Bolt, Livia; Dickson, John C; Sera, Terez

    2011-01-01

    A joint initiative of the European Association of Nuclear Medicine (EANM) Neuroimaging Committee and EANM Research Ltd. aimed to generate a European database of [(123)I]FP-CIT single photon emission computed tomography (SPECT) scans of healthy controls. This study describes the characterization...

  18. Social Franchising: A Blockbuster to Address Unmet Need for Family Planning and to Advance Toward the FP2020 Goal.

    Science.gov (United States)

    2015-06-17

    Social franchising has scaled-up provision of voluntary family planning, especially long-acting reversible contraceptives, across Africa and Asia at a rapid and remarkable pace. The approach should be pursued vigorously, especially in countries with a significant private-sector presence, to advance the FP2020 goal of providing access to modern contraception to 120 million additional clients by 2020.

  19. Impact of fowlpox-vectored Mycoplasma gallisepticum vaccine Vectormune FP MG on layer hen egg production and egg quality parameters.

    Science.gov (United States)

    Leigh, S A; Branton, S L; Evans, J D; Collier, S D

    2013-12-01

    This study was conducted to determine the impact of vaccination with Vectormune FP MG on egg production and egg quality characteristics of Single Comb White Leghorn hens. Due to questions of the efficacy of this vaccine in preventing Mycoplasma gallisepticum-mediated pathology, the ability of this vaccine to protect against postproduction-peak egg losses associated with F-strain M. gallisepticum (FMG) vaccination was also investigated. Vaccination with Vectormune FP MG did not result in any significant change in egg production or egg quality parameters compared with control (unvaccinated) hens. Subsequent revaccination with FMG at 45 wk of age (woa) yielded no impact on egg production or egg quality parameters of Vectormune FP MG vaccinated hens, unlike prior results for postproduction-peak vaccination of M. gallisepticum-clean hens with FMG, which exhibited a drop in egg production of approximately 6%. No difference in egg size distribution was observed for any of the treatment groups before or after FMG revaccination. These results suggest that hens can be safely vaccinated with Vectormune FP MG as pullets and can be revaccinated with a live M. gallisepticum vaccine such as FMG at a later date with no deleterious effects on egg production or egg or eggshell quality parameters.

  20. FP7 HBB-Next, a proposal for a European 7th Framework Project on next-generation Hybrid Broadcast Broadband

    NARCIS (Netherlands)

    Deventer, M.O. van; Niamut, O.A.

    2011-01-01

    This is the FP7 proposal HBB-Next: Next-Generation Hybrid Broadcast Broadband. It was submitted on 18 January 2011 for FP7 call no.7, objective 1.5a. So far, Hybrid Broadcast Internet applications have only linked Internet and broadcast content by offering over‐the‐top On‐Demand content in addition

  1. FP7 HBB-Next, a proposal for a European 7th Framework Project on next-generation Hybrid Broadcast Broadband

    NARCIS (Netherlands)

    Deventer, M.O. van; Niamut, O.A.

    2011-01-01

    This is the FP7 proposal HBB-Next: Next-Generation Hybrid Broadcast Broadband. It was submitted on 18 January 2011 for FP7 call no.7, objective 1.5a. So far, Hybrid Broadcast Internet applications have only linked Internet and broadcast content by offering over‐the‐top On‐Demand content in addition

  2. Performance of 6FDA–6FpDA polyimide for propylene/propane separations

    KAUST Repository

    Das, Mita

    2010-12-01

    This work addresses the challenges faced by previous researchers with 6FDA-6FpDA polyimide for propylene/propane separations due to plasticization. A study of film annealing temperature is reported to optimize plasticization suppression in elevated temperature permeation on properly annealed dense films made with high molecular weight polymer. A detailed analysis of pure and mixed gas results using different permeability models is shown in this work. The annealing effects in terms of plasticization suppression and permeability and selectivity changes are discussed in detail. According to our best knowledge, this is for the first time plasticization suppression for propylene/propane has been reported with any polyimide dense film membrane. Results of pure gas sorption experiments using a pressure decay method with un-annealed and annealed films are discussed and used to analyze the permeation data using the dual-mode model. Mixed gas permeation results also are explained with dual mode and bulk flow transport models. © 2010 Elsevier B.V.

  3. APhoRISM FP7 project: the Multi-platform volcanic Ash Cloud Estimation (MACE) infrastructure

    Science.gov (United States)

    Merucci, Luca; Corradini, Stefano; Bignami, Christian; Stramondo, Salvatore

    2014-05-01

    APHORISM is an FP7 project that aims to develop innovative products to support the management and mitigation of the volcanic and the seismic crisis. Satellite and ground measurements will be managed in a novel manner to provide new and improved products in terms of accuracy and quality of information. The Multi-platform volcanic Ash Cloud Estimation (MACE) infrastructure will exploit the complementarity between geostationary, and polar satellite sensors and ground measurements to improve the ash detection and retrieval and to fully characterize the volcanic ash clouds from source to the atmosphere. The basic idea behind the proposed method consists to manage in a novel manner, the volcanic ash retrievals at the space-time scale of typical geostationary observations using both the polar satellite estimations and in-situ measurements. The typical ash thermal infrared (TIR) retrieval will be integrated by using a wider spectral range from visible (VIS) to microwave (MW) and the ash detection will be extended also in case of cloudy atmosphere or steam plumes. All the MACE ash products will be tested on three recent eruptions representative of different eruption styles in different clear or cloudy atmospheric conditions: Eyjafjallajokull (Iceland) 2010, Grimsvotn (Iceland) 2011 and Etna (Italy) 2011-2012. The MACE infrastructure will be suitable to be implemented in the next generation of ESA Sentinels satellite missions.

  4. APhoRISM FP7 project: the A Priori information for Earthquake damage mapping method

    Science.gov (United States)

    Bignami, Christian; Stramondo, Salvatore; Pierdicca, Nazzareno

    2014-05-01

    The APhoRISM - Advanced PRocedure for volcanIc and Seismic Monitoring - project is an FP7 funded project, which aims at developing and testing two new methods to combine Earth Observation satellite data from different sensors, and ground data for seismic and volcanic risk management. The objective is to demonstrate that this two types of data, appropriately managed and integrated, can provide new improved products useful for seismic and volcanic crisis management. One of the two methods deals with earthquakes, and it concerns the generation of maps to address the detection and estimate of damage caused by a seism. The method is named APE - A Priori information for Earthquake damage mapping. The use of satellite data to investigate earthquake damages is not an innovative issue. Indeed, a wide literature and projects have addressed and focused such issue, but usually the proposed approaches are only based on change detection techniques and/or classifications algorithms. The novelty of APhoRISM-APE relies on the exploitation of a priori information derived by: - InSAR time series to measure surface movements - shakemaps obtained from seismological data - vulnerability information. This a priori information is then integrated with change detection map from earth observation satellite sensors (either Optical or Synthetic Aperture Radar) to improve accuracy and to limit false alarms.

  5. The ULISSE FP7 project new system for data exploration and dissemination

    Science.gov (United States)

    Carotenuto, Luigi; Rothkaehl, Hanna; Berthier, Audrey; Słomińska, Ewa

    2010-05-01

    The ULISSE FP7 project is aimed at providing the users with tools for improving data valorisation and exploitation of European space science experimentation. The activities are aimed at increasing the involvement of specialized communities and the awareness of general public.ULISSE will provide scientific and technical data concerning most scientific disciplines, as Life Sciences including Space Medicine and Exobiology, Biotechnology, Material and Fluid Sciences, Space Science. Data that will be available through ULISSE concern previous space experiments on ISS as well as data from other space platforms, like sounding rockets, Foton capsule, Space Shuttle, etc. This dataset, coming from a wide ensemble of experiments, represents a relevant resource that ULISSE brings to a new life, exploited for testing and demonstrative purposes. A relevant part of the project foresees that data, services and tools are integrated through the ULISSE middleware platform, developing a distributed infrastructure for the distribution of the scientific data coming from space experiments. ULISSE expected benefits maximise the return from scientific space missions by maximizing the exploitation of available data and preparing the exploitation of future space mission and increase the public awareness about space research results and benefits involving a wider community also including educational bodies. The aim of this presentation is also to show the survey of space physics experiments performed on ISS.

  6. EGIDA FP7 European Project: Outcomes of the National Use Cases Workshop

    Science.gov (United States)

    Mazzetti, P.; Bonora, N.; McCallum, I.; Nativi, S.

    2011-12-01

    In the framework of the EGIDA Project (European Commission FP7), that aims to support the implementation of the GEOSS Science and Technology roadmap, a workshop was held for the identification and analysis of European National contributions across a wide range of GEOSS SBAs (Social Benefit Areas), characterised through a bottom-up approach to GEOSS. During the workshop organization phase it was decided to address the activities not only to the identification of further examples showcasing GEOSS at work, but also to provide to the European Commission and GEOSS: a) elements to improve the national/regional contribution to GEOSS; b) elements to make the national contribution sustainable; and c) practices, commonalities and needs for further replication processes. The workshop collected 17 contributions from various European research institutes, programmes, projects and academia. The results of the workshop have been analysed in terms of practices, commonalities and needs, and they have been grouped into nine issues, such as: a) organising & catalysing resources, b) reuse and replication, c) promote data sharing, d) raise awareness for changing culture, e) ICT supporting activities & knowledge transfer, f) national GEO implementation & also governance, g) quick wins, h) scientific engagement in GEOSS and i) possible improvement of GEOSS at the EU level.

  7. Modeling structure and spectra of the kindling fluorescent protein asFP595

    Science.gov (United States)

    Collins, Jack R.; Topol, Igor A.; Savitsky, Alexander P.; Nemukhin, Alexander V.

    2011-03-01

    Modern computational approaches based on quantum mechanical methods to characterize structures and optical spectra of biological chromophores in proteins are intensively used to gain knowledge of events occurring upon of their photoexcitation. Primary attention is paid to the species from the family of the green fluorescent protein applied as biomarkers in living cells. We apply quantum chemical approaches for accurate calculations of the structures of the chromophore binding pockets and to estimate spectral bands corresponding to the S0-S1 optical transitions of the intriguing kindling protein asFP595. Its precursor, the chromoprotein asCP from the sea anemony Anemonia sulcata is characterized by distinctive spectral properties: at low light intensities the wild-type protein is weakly fluorescent with the very low quantum yield, however, high intensity irradiation with green light leads to a drastic increase of quantum yield. This phenomenon is now termed "kindling". In simulations, the model system is designed as a molecular cluster constructed on the basis of available crystal structures of the related protein. The equilibrium geometry of the cluster is optimized using density functional theory approximations. The vertical excitation energies corresponding to the S0-S1 transitions are computed by using the semiempirical ZINDO technique. A special attention is paid to evaluate effects of point mutations in the vicinity of the chromophore group. Theoretical data provide important information on the chromophore properties aiming to interpret the results of experimental studies and applications of this fluorescent protein.

  8. FP/FIFO scheduling: coexistence of deterministic and probabilistic QoS guarantees

    Directory of Open Access Journals (Sweden)

    Pascale Minet

    2007-01-01

    Full Text Available In this paper, we focus on applications having quantitative QoS (Quality of Service requirements on their end-to-end response time (or jitter. We propose a solution allowing the coexistence of two types of quantitative QoS garantees, deterministic and probabilistic, while providing a high resource utilization. Our solution combines the advantages of the deterministic approach and the probabilistic one. The deterministic approach is based on a worst case analysis. The probabilistic approach uses a mathematical model to obtain the probability that the response time exceeds a given value. We assume that flows are scheduled according to non-preemptive FP/FIFO. The packet with the highest fixed priority is scheduled first. If two packets share the same priority, the packet arrived first is scheduled first. We make no particular assumption concerning the flow priority and the nature of the QoS guarantee requested by the flow. An admission control derived from these results is then proposed, allowing each flow to receive a quantitative QoS guarantee adapted to its QoS requirements. An example illustrates the merits of the coexistence of deterministic and probabilistic QoS guarantees.

  9. Biohydrometallurgy applied to exploitation of black shale resources: Overview of Bioshale FP6 European project

    Institute of Scientific and Technical Information of China (English)

    P.D'HUGUES; P.SPOLAORE; Bioshale Consortium

    2008-01-01

    Bioshale project,co-funded by the European Commission (FP6 programme),started in October 2004 and finished in October 2007.The main objective of this project was to define innovative biotechnological processes for "eco-efficient" exploitation of black shale ores.The black shale ores contain base,precious and high-tech metals but also high contents of organic matter that handicap metal recovery by conventional techniques.Three world class black shale deposits were chosen as targets of the R&D actions.These include one deposit that existed under natural conditions (Talvivaara,Finland),one currently in process (Lubin,Poland) and one after mining (Mansfeld,Germany).The main technical aspects of the work plan can be summarized as follows:evaluation of the geological resources and selection of metal-bearing components; selection of biological consortia to be tested for metal recovery; assessment of bioprocessing routes,including hydrometallurgical processing for metals recovery; techno-economic evaluation of new processes including social and environmental impacts.An overview of the main results obtained by the 13 European partners (from 8 countries) involved in this completed research programme is given in this work.

  10. Comparison of LECO FP-228 "nitrogen determinator" with AOAC copper catalyst Kjeldahl method for crude protein.

    Science.gov (United States)

    Sweeney, R A; Rexroad, P R

    1987-01-01

    The LECO FP-228 "Nitrogen Determinator" was compared with the AOAC copper catalyst Kjeldahl method, 7.033-7.037, for the determination of crude protein in feed materials. The completely microprocessor-controlled instrument determines nitrogen by measuring the nitrogen gas following combustion of the sample; it was easy to operate and broadly applicable. A wide variety of feed materials of various nitrogen levels were analyzed in one mixed sequence. Results were precise, accurate, and rapid. Analysis time for one sample was approximately 3 min. Fourteen samples containing 2.5-15.5% N were selected for study and consisted of meals, grains, forages, and standard organic materials. The overall mean for the 14 samples by the LECO combustion method was 8.61% N compared with an overall mean of 8.58% N for the AOAC Kjeldahl method. Within-sample standard deviations for the LECO combustion method ranged from 0.013 to 0.052% N with a pooled standard deviation (SD) of 0.033% N for the 14 samples. Standard deviations for the AOAC Kjeldahl method ranged from 0.006 to 0.035% N with a pooled SD of 0.022% N. Combined average recovery of nitrogen from tryptophan, lysine-HCl, and EDTA determined by the LECO combustion method was 99.94% compared to 99.88% determined by the AOAC Kjeldahl method.

  11. The severe accident research programme PHEBUS F.P.: First results and future tests

    Energy Technology Data Exchange (ETDEWEB)

    Schwarz, M. [Institut de Protection et de Surete Nucleaire IPSN, Saint Paul Lez Durance (France); Hardt, P. von der [Joint Research Centre - Safety Technology Institute, Saint Paul Lez Durance (France)

    1996-03-01

    PHEBUS FP is an international programme, managed by the French Institut de Protection et de Surete Nucleaire, Electricite de France and the European Commission in close collaboration with the USNRC (US), COG (Canada), NUPEC and JAERI (Japan) and KAERI (South Korea). Its objective is to investigate through a series of in-pile integral experiments, key phenomena involved in LWR severe accident such as the degradation of core materials up to molten pool, the subsequent release of fission products and of structural materials, their transport in the cooling system and their deposition in the containment with a special emphasis on the volatility of iodine. After a general programme description, the paper focuses on the status of analysis of the first test FPT-0, which involved trace irradiated fuel and which has shown some quite unexpected results regarding fuel degradation and iodine behaviour, and on the upcoming test FPT-1 which will use irradiated fuel. The status of the preparation of the remaining tests of the programme is also presented.

  12. Role of prostaglandin receptor EP2 in the regulations of cancer cell proliferation, invasion, and inflammation.

    Science.gov (United States)

    Jiang, Jianxiong; Dingledine, Ray

    2013-02-01

    Population studies, preclinical, and clinical trials suggest a role for cyclooxygenase-2 (COX-2, PTGS2) in tumor formation and progression. The downstream prostanoid receptor signaling pathways involved in tumorigenesis are poorly understood, although prostaglandin E2 (PGE(2)), a major COX-2 metabolite which is usually upregulated in the involved tissues, presumably plays important roles in tumor biology. Taking advantage of our recently identified novel selective antagonist for the EP2 (PTGER2) subtype of PGE(2) receptor, we demonstrated that EP2 receptor activation could promote prostate cancer cell growth and invasion in vitro, accompanied by upregulation of the tumor-promoting inflammatory cytokines, such as IL-1β and IL-6. Our results suggest the involvement of prostaglandin receptor EP2 in cancer cell proliferation and invasion possibly via its inflammatory actions, and indicate that selective blockade of the PGE(2)-EP2 signaling pathway via small molecule antagonists might represent a novel therapy for tumorigenesis.

  13. Eicosanoid receptors: Targets for the treatment of disrupted intestinal epithelial homeostasis.

    Science.gov (United States)

    Moreno, Juan J

    2017-02-05

    The importance of cyclooxygenase and lipoxygenase pathways and the consequent eicosanoid synthesis in the physiology and pathophysiology of the intestinal epithelium is currently being established. Each eicosanoid (prostanoid, leukotriene, hydroxyeicosatetraenoic acid) preferentially recognizes one or more receptors coupled to one or more signal-transduction processes. This overview focuses on the role of eicosanoid receptors in the maintenance of intestinal epithelium physiology through the control of proliferation/differentiation/apoptosis processes. Furthermore, it is reported that the role of these receptors on the regulation of the barrier function of the intestinal epithelium have arisen through the regulation of absorption/secretion processes, tight-junction state and the control of the intestinal immune response. Also, this review considers the implication of AA cascade in the disruption of epithelial homeostasis during inflammatory bowel diseases and colorectal cancer as well as the therapeutic values and potential of the eicosanoid receptors as novel targets for the treatments of the pathologies above mentioned.

  14. Gene : CBRC-MMUS-03-0082 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available ostaglandin F receptor [Mus musculus] sp|P43117|PF2R_MOUSE Prostaglandin F2-alpha receptor (Prostanoid FP re...CBRC-MMUS-03-0082 3 A Prostanoids receptors PF2R_MOUSE 0.0 100% ref|NP_032992.1| pr...ceptor) (PGF receptor) (PGF2 alpha receptor) dbj|BAA04251.1| prostaglandin F receptor [Mus musculus] dbj|BAC...40021.1| unnamed protein product [Mus musculus] dbj|BAC80245.1| prostaglandin F2alpha receptor [Mus mus...culus] dbj|BAC80246.1| prostaglandin F2alpha receptor [Mus musculus] gb|AAH64794.1| Pr

  15. Prediction of the Human EP1 Receptor Binding Site by Homology Modeling and Molecular Dynamics Simulation.

    Science.gov (United States)

    Zare, Behnoush; Madadkar-Sobhani, Armin; Dastmalchi, Siavoush; Mahmoudian, Masoud

    2011-01-01

    The prostanoid receptor EP1 is a G-protein-coupled receptor (GPCR) known to be involved in a variety of pathological disorders such as pain, fever and inflammation. These receptors are important drug targets, but design of subtype specific agonists and antagonists has been partially hampered by the absence of three-dimensional structures for these receptors. To understand the molecular interactions of the PGE2, an endogen ligand, with the EP1 receptor, a homology model of the human EP1 receptor (hEP1R) with all connecting loops was constructed from the 2.6 Å resolution crystal structure (PDB code: 1L9H) of bovine rhodopsin. The initial model generated by MODELLER was subjected to molecular dynamics simulation to assess quality of the model. Also, a step by step ligand-supported model refinement was performed, including initial docking of PGE2 and iloprost in the putative binding site, followed by several rounds of energy minimizations and molecular dynamics simulations. Docking studies were performed for PGE2 and some other related compounds in the active site of the final hEP1 receptor model. The docking enabled us to identify key molecular interactions supported by the mutagenesis data. Also, the correlation of r(2)=0.81 was observed between the Ki values and the docking scores of 15 prostanoid compounds. The results obtained in this study may provide new insights toward understanding the active site conformation of the hEP1 receptor and can be used for the structure-based design of novel specific ligands.

  16. Integrated Medium for Planetary Exploration (IMPEx): a new EU FP7-SPACE project

    Science.gov (United States)

    Khodachenko, M. L.; Genot, V. N.; Kallio, E. J.; Alexeev, I. I.; Modolo, R.; Al-Ubaidi, T.; André, N.; Gangloff, M.; Schmidt, W.; Belenkaya, E. S.; Topf, F.; Stoeckler, R.

    2011-12-01

    The FP7-SPACE project Integrated Medium for Planetary Exploration (IMPEx) has started in June 2011. It will create an interactive framework for exploitation of space missions' data. Data analysis and visualization will be based on the advanced computational models of the planetary environments. Specifically, the 'modeling sector' of IMPEx is formed of four well established numerical codes and their related computational infrastructures: 1) 3D hybrid modeling platform HYB for the study of planetary plasma environments, hosted at FMI; 2) an alternative 3D hybrid modeling platform, hosted at LATMOS; 3) MHD modelling platform GUMICS for 3D terrestrial magnetosphere, hosted at FMI; and 4) the global 3D Paraboloid Magnetospheric Model for simulation of magnetospheres of different Solar System objects, hosted at SINP. Modelling results will be linked to the corresponding experimental data from space and planetary missions via several online tools: 1/ AMDA (Automated Multi-Dataset Analysis, http://cdpp-amda.cesr.fr/) which provides cross-linked visualization and operation of experimental and numerical modelling data, 2/ 3DView which will propose 3D visualization of spacecraft trajectories in simulated and observed environments, and 3/ "CLWeb" software which enables computation of various micro-scale physical products (spectra, distribution functions, etc.). In practice, IMPEx is going to provide an external user with an access to an extended set of space and planetary missions' data and powerful, world leading computing models, equipped with advanced visualization tools. Via its infrastructure, IMPEx will bring the data and models outside of the mission teams and specialized modelling groups making them accessible and useful for a broad planetary science community.

  17. Low power reconfigurable FP-FFT core with an array of folded DA butterflies

    Science.gov (United States)

    Beulet Paul, Augusta Sophy; Raju, Srinivasan; Janakiraman, Raja

    2014-12-01

    A variable length (32 ~ 2,048), low power, floating point fast Fourier transform (FP-FFT) processor is designed and implemented using energy-efficient butterfly elements. The butterfly elements are implemented using distributed arithmetic (DA) algorithm that eliminates the power-consuming complex multipliers. The FFT computations are scheduled in a quasi-parallel mode with an array of 16 butterflies. The nodes of the data flow graph (DFG) of the FFT are folded to these 16 butterflies for any value of N by the control unit. Register minimization is also applied after folding to decrease the number of scratch pad registers to (log 2 N - 1) × 16. The real and imaginary parts of the samples are represented by 32-bit single-precision floating point notation to achieve high precision in the results. Thus, each sample is represented using 64 bits. Twiddle factor ROM size is reduced by 25% using the symmetry of the twiddle factors. Reconfigurability based on the sample size is achieved by the control unit. This distributed floating point arithmetic (DFPA)-based design of FFT processor implemented in 45-nm process occupies an area of 0.973 mm2 and dissipates a power of 68 mW at an operating frequency of 100 MHz. When compared with FFT processor designed in the same technology with multiplier-based butterflies, this design shows 33% less area and 38% less power. The throughput for 2,048-point FFT is 222 KS/s and the energy spent per FFT is 7.4 to 14 nJ for 64 to 2,048 points being one among the most energy-efficient FFT processors.

  18. Evolution of clinical features in possible DLB depending on FP-CIT SPECT result

    Science.gov (United States)

    Moreno, Emilio; Thomas, Alan; Inglis, Fraser; Tabet, Naji; Stevens, Tim; Whitfield, Tim; Aarsland, Dag; Rainer, Michael; Padovani, Alessandro

    2016-01-01

    Objective: To test the hypothesis that core and suggestive features in possible dementia with Lewy bodies (DLB) would vary in their ability to predict an abnormal dopamine transporter scan and therefore a follow-up diagnosis of probable DLB. A further objective was to assess the evolution of core and suggestive features in patients with possible DLB over time depending on the 123I-FP-CIT SPECT scan result. Methods: A total of 187 patients with possible DLB (dementia plus one core or one suggestive feature) were randomized to have dopamine transporter imaging or to follow-up without scan. DLB features were compared at baseline and at 6-month follow-up according to imaging results and follow-up diagnosis. Results: For the whole cohort, the baseline frequency of parkinsonism was 30%, fluctuations 29%, visual hallucinations 24%, and REM sleep behavior disorder 17%. Clinician-rated presence of parkinsonism at baseline was significantly (p = 0.001) more frequent and Unified Parkinson’s Disease Rating Scale (UPDRS) score at baseline was significantly higher (p = 0.02) in patients with abnormal imaging. There was a significant increase in UPDRS score in the abnormal scan group over time (p < 0.01). There was relatively little evolution of the rest of the DLB features regardless of the imaging result. Conclusions: In patients with possible DLB, apart from UPDRS score, there was no difference in the evolution of DLB clinical features over 6 months between cases with normal and abnormal imaging. Only parkinsonism and dopamine transporter imaging helped to differentiate DLB from non-DLB dementia. PMID:27511183

  19. Analysis of FP aerosol behavior in piping in WIND project. Contract research

    Energy Technology Data Exchange (ETDEWEB)

    Hidaka, Akihide; Maruyama, Yu; Shibazaki, Hiroaki; Maeda, Akio; Harada, Yuhei [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment; Nagashima, Toshio; Yoshino, Takehito; Sugimoto, Jun

    1998-07-01

    In the analyses of aerosol behavior test in piping in WIND (Wide Range Piping Integrity Demonstration) project at Japan Atomic Energy Research Institute (JAERI), ART code developed by JAERI and VICTORIA code developed by Sandia National Laboratories are used to perform WIND test analysis and to validate the models in the both codes. It is noted that VICTORIA code is supposed to be used as reference code of ART at JAERI. As a part of these activities, WIND Aerosol Deposition tests (WAD4 and 5) and FP aerosol behaviors in safety relief valve (SRV) line during BWR high pressure sequence which will be performed in future WIND experiment were analyzed with ART and VICTORIA codes. The present analyses showed that the portion and mass with relatively large amount of cesium iodide (CsI) deposition observed in WAD4 and 5 tests were reasonably reproduced by ART and VICTORIA codes. A difference was found in condensation and revaporization behaviors of gaseous CsI between the two codes. VICTORIA overestimated the condensed mass of CsI vapor while ART reproduced better the experimental data than the VICTORIA calculation. Further investigation is needed for this issue. Although the deposition mass at the pipe connection part in WAD4 and 5 experiments was not measured, the mass at that portion will be measured from next experiment because relatively large amount of CsI could be deposited there and the measurement is considered to be useful for code verification. The predicted principal aerosol deposition mechanism in SRV line is turbulence. Temperature of SRV line could increase by about 300 K by decay heat from deposited FPs. However, the SRV line made of carbon steel would not be failed because the predicted temperature is still far lower than the melting temperature of carbon steel. (author)

  20. Modulation of JB6 Mouse Epidermal Cell Transformation Response by the Prostaglandin F2 Alpha Receptor

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Thomas J.; Markillie, Lye MENG.; Chrisler, William B.; Vielhauer, George A.; Regan, John W.

    2002-12-01

    Prostaglandin F2a (PGF2a) has been associated with the modulation of clonal selection processes in the mouse skin model of carcinogenesis. We have investigated whether JB6 mouse epidermal cells express a functional PGF2a receptor (FP) coupled to the regulation of anchorage-dependent and -independent growth. Treatment of JB6 cells with a FP receptor ligand (fluprostenol) potently (pM-nM) increased anchorage-dependent and -independent growth, as determined by a battery of in vitro assays. Treatment of JB6 cells with PGF2a and fluprostenol increased inositol phospholipid accumulation and extracellular signal regulated kinase (ERK) activity, consistent with FP receptor-related signaling. FP receptor mRNA was detected by reverse transcription-polymerase chain reaction and a radiolabel binding assay determined the average specific [3H]PGF2a binding to be 8.25 + 0.95 fmol/mg protein. Treatment of cells with fluprostenol as a single exposure resulted in a significant increase in anchorage-dependent and -independent growth in media containing low (0.1-0.5%), but not high (5%) concentrations of fetal bovine serum (FBS). In contrast, treatment of cells with fluprostenol at two day intervals resulted in a more robust growth response under anchorage-dependent conditions only in media containing low FBS concentrations; and under anchorage-independent conditions only in media containing high FBS concentrations. ERK activation and colony size were increased by cotreatment of JB6 cells with EGF and fluprostenol to a greater extent than either treatment alone, while the cotreatment effect on colony number appeared to be simply additive. In summary, FBS concentration and signal oscillation exert pronounced effects on the biological response to a FP receptor agonist. The data raise the possibility that the FP receptor may independently contribute to clonal selection processes, but may play a more important role as a response modifier.

  1. Long-term orbital period behaviour of low mass ratio contact binaries GR Vir and FP Boo

    Science.gov (United States)

    Ćetinkaya, Halil; Soydugan, Faruk

    2017-02-01

    In this study, we investigated orbital period variations of two low mass ratio contact binaries GR Vir and FP Boo based on published minima times. From the O-C analysis, it was found that FP Boo indicates orbital period decrease while the period of GR Vir is increasing. Mass transfer process was used to explain increase and decrease in the orbital periods. In the O-C diagrams of both systems periodic variations also exist. Cyclic changes can be explained as being the result of a light-travel time effect via a third component around the eclipsing binaries. In order to interpret of cyclic orbital period changes for GR Vir, which has late-type components, possible magnetic activity cycles of the components have been also considered.

  2. Sensitivity analysis for CORSOR models simulating fission product release in LOFT-LP-FP-2 severe accident experiment

    Energy Technology Data Exchange (ETDEWEB)

    Hoseyni, Seyed Mohsen [Islamic Azad Univ., Tehran (Iran, Islamic Republic of). Dept. of Basic Sciences; Islamic Azad Univ., Tehran (Iran, Islamic Republic of). Young Researchers and Elite Club; Pourgol-Mohammad, Mohammad [Sahand Univ. of Technology, Tabriz (Iran, Islamic Republic of). Dept. of Mechanical Engineering; Yousefpour, Faramarz [Nuclear Science and Technology Research Institute, Tehran (Iran, Islamic Republic of)

    2017-03-15

    This paper deals with simulation, sensitivity and uncertainty analysis of LP-FP-2 experiment of LOFT test facility. The test facility simulates the major components and system response of a pressurized water reactor during a LOCA. MELCOR code is used for predicting the fission product release from the core fuel elements in LOFT LP-FP-2 experiment. Moreover, sensitivity and uncertainty analysis is performed for different CORSOR models simulating release of fission products in severe accident calculations for nuclear power plants. The calculated values for the fission product release are compared under different modeling options to the experimental data available from the experiment. In conclusion, the performance of 8 CORSOR modeling options is assessed for available modeling alternatives in the code structure.

  3. X-ray diffraction analysis and molecular-replacement solution of the cyan fluorescent protein dsFP483

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Meitian; Patel, Hetal N.; Wachter, Rebekka M., E-mail: rwachter@asu.edu [Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona (United States)

    2005-10-01

    The coral-derived cyan fluorescent protein dsFP483 has been crystallized and diffraction data were collected to 2.1 Å. A molecular-replacement solution is presented for 83% of the protein contents of the asymmetric unit. A novel cyan fluorescent protein, dsFP483 from the coral Discosoma striata, has been crystallized. Diffraction data were collected to 2.1 Å and processed in space group C2. Molecular-replacement methods were applied using the closely related red fluorescent protein DsRed as a search model. The asymmetric unit appears to contain six protein molecules (1.5 tetramers), five of which (83%) could be located by the molecular-replacement searches.

  4. Employing injection-locked FP LDs to set up a hybrid CATV/MW/MMW WDM light wave transmission system.

    Science.gov (United States)

    Lin, Chun-Yu; Lu, Hai-Han; Li, Chung-Yi; Wu, Po-Yi; Peng, Peng-Chun; Jhang, Tai-Wei; Lin, Che-Yu

    2014-07-01

    A hybrid cable television (CATV)/microwave (MW)/millimeter-wave (MMW) wavelength-division-multiplexing (WDM) light wave transmission system based on injection-locked Fabry-Perot laser diodes (FP LDs) is proposed and demonstrated. Different from conventional hybrid WDM light wave transmission systems, which need wavelength-selected distributed feedback laser diodes to support various services, the proposed systems employ injection-locked FP LDs to provide multiple applications. Over a 40 km single-mode fiber transport, impressive performances of carrier-to-noise ratio/composite second-order/composite triple-beat/bit error rate are obtained for 550 MHz CATV/20 GHz MW/40 GHz MMW/60 GHz MMW signal transmissions. Such a hybrid WDM light wave transmission system would be attractive for fiber links to provide broadband integrated services.

  5. Intranasal dopamine reduces in vivo [123I]FP-CIT binding to striatal dopamine transporter: correlation with behavioral changes and evidence for Pavlovian conditioned dopamine response

    Directory of Open Access Journals (Sweden)

    Maria A de Souza Silva

    2016-04-01

    Full Text Available Purpose: Dopamine (DA, which does not cross the blood-brain barrier, has central and behavioral effects when administered via the nasal route. Neither the mechanisms of central action of intranasal dopamine (IN-DA, nor its mechanisms of diffusion and transport into the brain are well understood. We here examined whether IN-DA application influences dopamine transporter (DAT binding in the dorsal striatum and assessed the extent of binding in relation to motor and exploratory behaviors. We hypothesized that, based on the finding of increased extracellular DA in the striatum induced by application of IN-DA, binding of [123I]FP-CIT to the DAT should be decreased due to competition at the receptor.Methods: Rats were administered intranasal application of 3 mg/kg IN-DA and vehicle (VEH, with IN-DA injection either preceding or following VEH. Then motor and exploratory behaviors (traveled distance, velocity, center time, sitting, rearing, head-shoulder motility, grooming were assessed for 30 min in an open field prior to administration of [123I]FP-CIT. DAT binding after IN-DA and VEH was measured with small animal SPECT two hours following administration of the radioligand. Results: 1 After IN-DA application, striatal DAT binding was significantly lower as compared to VEH, indicating that the nasally delivered dopamine had central action and increased DA levels comparable to that found previously with L-DOPA administration. 2 DAT binding in response to intranasal VEH was lower when IN-DA application preceded VEH treatment. This finding is suggestive of Pavlovian conditioning of DA at the level of the DAT, since the DA treatment modified (decreased the binding in response to the subsequent VEH treatment. VEH treatment also reduced motor and exploratory behaviors more when applied before, as compared to when it followed IN-DA application, also indicative of behavioral Pavlovian conditioning akin to that found upon application of various psychostimulant

  6. Intranasal Dopamine Reduces In Vivo [123I]FP-CIT Binding to Striatal Dopamine Transporter: Correlation with Behavioral Changes and Evidence for Pavlovian Conditioned Dopamine Response

    Science.gov (United States)

    de Souza Silva, Maria A.; Mattern, Claudia; Decheva, Cvetana; Huston, Joseph P.; Sadile, Adolfo G.; Beu, Markus; Müller, H.-W.; Nikolaus, Susanne

    2016-01-01

    Purpose: Dopamine (DA), which does not cross the blood-brain barrier, has central and behavioral effects when administered via the nasal route. Neither the mechanisms of central action of intranasal dopamine (IN-DA), nor its mechanisms of diffusion and transport into the brain are well understood. We here examined whether IN-DA application influences dopamine transporter (DAT) binding in the dorsal striatum and assessed the extent of binding in relation to motor and exploratory behaviors. We hypothesized that, based on the finding of increased extracellular DA in the striatum induced by application of IN-DA, binding of [123I]FP-CIT to the DAT should be decreased due to competition at the receptor. Methods: Rats were administered 3 mg/kg IN-DA and vehicle (VEH), with IN-DA injection either preceding or following VEH. Then motor and exploratory behaviors (traveled distance, velocity, center time, sitting, rearing, head-shoulder motility, grooming) were assessed for 30 min in an open field prior to administration of [123I]FP-CIT. DAT binding after IN-DA and VEH was measured with small animal SPECT 2 h following administration of the radioligand. Results: (1) After IN-DA application, striatal DAT binding was significantly lower as compared to VEH, indicating that the nasally delivered DA had central action and increased DA levels comparable to that found previously with L-DOPA administration; and (2) DAT binding in response to intranasal VEH was lower when IN-DA application preceded VEH treatment. This finding is suggestive of Pavlovian conditioning of DA at the level of the DAT, since the DA treatment modified (decreased) the binding in response to the subsequent VEH treatment. VEH treatment also reduced motor and exploratory behaviors more when applied before, as compared to when it followed IN-DA application, also indicative of behavioral Pavlovian conditioning akin to that found upon application of various psychostimulant drugs. Conclusions: The results: (a

  7. Scientific Opinion on the Pest Risk Analysis on Phytophthora ramorum prepared by the FP6 project RAPRA

    DEFF Research Database (Denmark)

    Baker, R.; Candresse, T.; Dormannsné Simon, E.

    2011-01-01

    The Panel on Plant Health was asked to deliver a scientific opinion on the Pest Risk Analysis on Phytophthora ramorum prepared by the FP6 project RAPRA, taking into account comments by Member States and additional information since RAPRA. P. ramorum is the oomycete causing sudden oak death...... research on P. ramorum across Europe. Regulatory work should keep updated with research results on P. ramorum and further development of the Japanese larch outbreaks....

  8. Increased brain temserotoneric transporter availability in adult migraineurs: ([18F]FP-CIT PET imaging pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Park, Eun Kyung [Dept. of Nuclear Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul (Korea, Republic of); Hwang, Yu Mi [Center for Research Information, Korea University, Seoul (Korea, Republic of); Chu, Min Kyung [Dept. of Neurology, Sacred Heart Hospital, Hallym University College of Medicine, Anyang (Korea, Republic of); Jung, Ki Young [Dept. of Neurology, Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2016-03-15

    Recent studies have proposed central serotonergic dysfunction as a major pathophysiology of migraine. We investigated serotonin transporter (SERT) availability in migraineurs using F-18-N-(3-fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl) nortropane ([18F]FP-CIT) positron emission tomography (PET). Brain [18F]FP-CIT PET images were obtained in eight women with migraine during headache free phase and 12 healthy adult women, 120 min after injection of 185 MBq. Non-displaceable binding potential (BP ND) of [18F]FP-CIT, which is an estimate of SERT availability, was calculated at the brainstem and compared with clinical parameters. BP ND at the brainstem was significantly higher in adult migraineurs (n = 6, 1.15 ± 0.17) than healthy subjects (0.95 ± 0.14) (p = 0.04). Healthy subjects demonstrated negative correlation between brainstem BP ND and age (r = −0.64, p = 0.02), whereas this age-related decline pattern was not found in the migraineurs. Severity of migraine attack was significantly correlated with brainstem BP ND (r = 0.66, p = 0.02), when age and duration of illness were corrected. Increased SERT availability in the brainstem of adult migraineurs indicates low serotonin neurotransmission during headache-free phase. Patients who experience more painful headaches have lower serotonin neurotransmission. [18F]FP-CIT PET is a useful in vivo imaging technique for evaluating brainstem SERT availability in migraineurs.

  9. Covalent binding of the organophosphorus agent FP-biotin to tyrosine in eight proteins that have no active site serine

    OpenAIRE

    Grigoryan, Hasmik; Li, Bin; Anderson, Erica K.; Xue, Weihua; Nachon, Florian; Lockridge, Oksana; Schopfer, Lawrence M.

    2009-01-01

    Organophosphorus esters (OP) are known to bind covalently to the active site serine of enzymes in the serine hydrolase family. It was a surprise to find that proteins with no active site serine are also covalently modified by OP. The binding site in albumin, transferrin, and tubulin was identified as tyrosine. The goal of the present work was to determine whether binding to tyrosine is a general phenomenon. Fourteen proteins were treated with a biotin-tagged organophosphorus agent called FP-b...

  10. Weighted composition operators from F(p, q, s) spaces to Bers-type spaces in the unit ball

    Institute of Scientific and Technical Information of China (English)

    L(U) Xiao-fen

    2009-01-01

    This paper deals with the boundedness and compactness of the weighted compo-sition operators from the F(p, q, s) spaces, including Hardy space, Bergman space, Q~p space,BMOA space, Besov space and α-Bloch space, to Bers-type spaces H_ν~∞( or little Bets-type spaces H_(ν,0)~∞ ), where ν is normal.

  11. The role and interactions of nitric oxide (NO), carbon monoxide (CO), and prostanoids in the pathogenesis of postoperative ileus in rats.

    Science.gov (United States)

    Korolkiewicz, R P; Sein-Anand, J; Ruczyński, J; Rekowski, P; Bieniaszewski, L; Chodorowski, Z; Petrusewicz, J; Ujda, M; Dabkowski, J; Bitel, M; Kato, S; Takeuchi, K

    2004-01-01

    The effects of heme oxygenase (HO) inhibitors, zinc-protoporphyrin-IX (ZnPP-IX), and tin protoporphyrin-IX (SnPP-IX) and their interactions with L-arginine/nitric oxide synthase (NOS) and cyclooxygenase (COX) pathways were investigated in postoperative ileus in rats. Intestinal transit was measured as Evans blue migration after skin incision, laparotomy or laparotomy plus gut evisceration and handling. Laparotomy and small intestinal manipulations increased blood plasma nitrites/nitrates level 1.88-fold. N(omega)-nitro-L-arginine methyl ester, indomethacin, a selective COX-1 blocker (resveratrol) and COX-2 antagonists (nimesulide, DuP-697, NS-398) reversed the additional inhibitory effects of gut manipulation subsequent to laparotomy. In contrast, N-(3-(aminomethyl)benzyl)acetamidine or S-methylisothiourea, highly selective inducible NOS blockers, remained ineffective. ZnPP-IX and SnPP-IX overturned the effects of laparotomy on dye propulsion, but were only partially effective after laparotomy and gut handling attenuating the additional inhibitory influences of gut manipulation, the intestinal transit reaching 89.21%, 92.87%, 53.46%, and 48.56% of respective controls transit. Salutary effects of L-NAME, ZnPP-IX, and SnPP-IX were dose-dependent, L-arginine or hemin (HO substrate) sensitive. Administration of indomethacin and resveratrol subsequent to SnPP-IX reversed the inhibitory effects of laparotomy and manipulation, amounting to 93.91% and 87.43% of controls. On the other hand, L-NAME injected after SnPP-IX abolished the salutary effects of the latter, study dye migration reached 25.18% of control rat. Therefore we demonstrated that nitric oxide, carbon monoxide, and prostanoids play a role in the pathogenesis of postoperative ileus albeit in different mechanisms. Laparotomy stimulated HO activity, whereas gut manipulation led to an excessive constitutive NOS stimulation accompanied by augmented prostanoid synthesis by COX-1. Unaffected synthesis of either NO

  12. Applications research in ultrasonic testing of carbon fiber composite based on an optical fiber F-p sensor

    Science.gov (United States)

    Shan, Ning

    2016-10-01

    Carbon fiber composite is widely applied to the field of aerospace engineering because of its excellent performance. But it will be able to form more defects in the process of manufacturing inevitably on account of unique manufacturing process. Meanwhile it has sophisticated structure and services in the bad environment long time. The existence of defects will be able to cause the sharp decline in component's performance when the defect accumulates to a certain degree. So the reliability and safety test demand of carbon fiber composite is higher and higher. Ultrasonic testing technology is the important means used for characteristics of component inspection of composite materials. Ultrasonic information detection uses acoustic transducer generally. It need coupling agent and is higher demand for the surface of sample. It has narrow frequency band and low test precision. The extrinsic type optical fiber F-P interference cavity structure is designed to this problem. Its optical interference model is studied. The initial length of F-P cavity is designed. The realtime online detection system of carbon fiber composite is established based on optical fiber F-P Ultrasound sensing technology. Finally, the testing experiment study is conducted. The results show that the system can realize real-time online detection of carbon fiber composite's defect effectively. It operates simply and realizes easily. It has low cost and is easy to practical engineering.

  13. Comparison of FP-CIT SPECT with F-DOPA PET in patients with de novo and advanced Parkinson's disease

    Energy Technology Data Exchange (ETDEWEB)

    Eshuis, S.A. [University Hospital Groningen, Department of Neurology, Groningen (Netherlands); University Hospital Groningen, Department of Nuclear Medicine, Groningen (Netherlands); Maguire, R.P.; Leenders, K.L. [University Hospital Groningen, Department of Neurology, Groningen (Netherlands); Jonkman, S.; Jager, P.L. [University Hospital Groningen, Department of Nuclear Medicine, Groningen (Netherlands)

    2006-02-01

    Diagnosis of Parkinson's disease (PD) can be difficult. F-DOPA PET is able to quantify striatal dopa decarboxylase activity and storage capacity of F-dopamine, but is expensive and not generally available. FP-CIT binds to the dopamine transporter, and FP-CIT SPECT is cheaper and more widely available, but has a lower resolution. The aim of this study was to compare these two methods in the same patients with different stages of PD to assess their power in demonstrating deficits of the striatal dopaminergic system. Thirteen patients with de novo PD and 17 patients with advanced PD underwent FP-CIT SPECT and static F-DOPA PET. After data transfer to standard stereotactic space, a template with regions of interest was used to sample values of the caudate, putamen and an occipital reference region. The outcome value was striato-occipital ratios. Patients were clinically examined in the ''off state'' (UPDRS-III and H and Y stage). Good correlations were found between striatal F-DOPA uptake and striatal FP-CIT uptake (r=0.78) and between putaminal F-DOPA uptake and putaminal FP-CIT uptake (r=0.84, both p<0.0001). Both striatal uptake of FP-CIT and that of F-DOPA correlated moderately with H and Y stage ({rho}=-0.52 for both techniques), UPDRS-III ({rho}=-0.38 for F-DOPA; {rho}=-0.45 for FP-CIT) and disease duration ({rho}=-0.59 for F-DOPA; {rho}=-0.49 for FP-CIT, all p<0.05). FP-CIT values correlate well with F-DOPA values. Both methods correlate moderately with motor scores and are equally able to distinguish patients with advanced PD from patients with de novo PD. (orig.)

  14. [O-methyl-{sup 11}C]{beta}-CIT-FP, a potential radioligand for quantitation of the dopamine transporter: Preparation, autoradiography, metabolite studies, and positron emission tomography examinations

    Energy Technology Data Exchange (ETDEWEB)

    Lundkvist, Camilla; Halldin, Christer; Swahn, Carl-Gunnar; Hall, Haakan; Karlsson, Per; Nakashima, Yoshifumi; Wang, Shaoyin; Milius, Richard A.; Neumeyer, John L.; Farde, Lars

    1995-10-01

    {beta}-CIT-FP [N-(3-fluoropropyl)-2{beta}-carbomethoxy-3{beta}-(4-iodophenyl)nortropane] is a cocaine analogue with a high affinity for the dopamine transporter. [O-methyl-{sup 11}C]{beta}-CIT-FP ([{sup 11}C]{beta}-CIT-FP) was prepared byO -alkylation of the free acid with [{sup 11}C]methyl iodide. The total radiochemical yield of [{sup 11}C]{beta}-CIT-FP was 50 to 60% with an overall synthesis time of 30 min. The radiochemical purity was >99%, and the specific radioactivity at time of injection was about 37 GBq/{mu}mol (1000 Ci/mmol). Autoradiographic examination of [{sup 11}C]{beta}-CIT-FP binding in human brain postmortem demonstrated specific binding in the caudate nucleus and putamen. Positron emission tomography (PET) examination of [{sup 11}C]{beta}-CIT-FP in a Cynomolgus monkey demonstrated accumulation in the striatum with a striatum-to-cerebellum ratio of about 8 after 60 min. Equilibrium in the striatum was attained within 70 to 90 min. The radioactivity ratios of thalamus/cerebellum and neocortex/cerebellum were about 2 and 1.5, respectively. In a displacement experiment, radioactivity in the striatum but not in the cerebellum was reduced after injection of {beta}-CIT, indicating that striatal radioactivity following injection of [{sup 11}C]{beta}-CIT-FP is associated with dopamine transporter sites and that the binding is reversible. The fraction of the total radioactivity in plasma representing [{sup 11}C]{beta}-CIT-FP determined by high-performance liquid chromatography (HPLC) was 84% at 15 min and 50% at 95 min. [{sup 11}C]{beta}-CIT-FP should be a useful PET radioligand for the quantitation of dopamine transporters in the human brain in vivo.

  15. Lipoic acid stimulates cAMP production via the EP2 and EP4 prostanoid receptors and inhibits IFN gamma synthesis and cellular cytotoxicity in NK cells

    OpenAIRE

    Salinthone, Sonemany; Schillace, Robynn V.; Marracci, Gail H.; Bourdette, Dennis N.; Carr, Daniel W.

    2008-01-01

    The antioxidant lipoic acid (LA) treats and prevents the animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE). In an effort to understand the therapeutic potential of LA in MS, we sought to define the cellular mechanisms that mediate the effects of LA on human natural killer (NK) cells, which are important in innate immunity as the first line of defense against invading pathogens and tumor cells. We discovered that LA stimulates cAMP production in NK cells ...

  16. Comparison of MEK/ERK pathway inhibitors on the upregulation of vascular G-protein coupled receptors in rat cerebral arteries

    DEFF Research Database (Denmark)

    Sandhu, Hardip; Ansar, Saema; Edvinsson, Lars

    2010-01-01

    on translational level and increased respective contractions. The prostanoid TP receptor mediated contraction curve was left-wards shifted by organ culture. Organ culture was associated with elevated pERK1/2 in the vascular smooth muscle cells: the MEK1/2 inhibitor U0126 attenuated the endothelin ET(B) receptor......Organ culture is an in vitro method for investigating cellular mechanisms involved in upregulation of vasocontractile G-protein coupled receptors. We hypothesize that mitogen-activated-protein kinase (MEK) and/or extracellular-signal-regulated kinase (ERK) specific inhibitors will attenuate the G......-protein coupled receptor expression following organ culture. Rat cerebral arteries were incubated 48h in the presence of MEK/ERK specific inhibitors U0126, PD98059, SL327, or AG126 for different time periods. Contractile responses by activation of endothelin receptor type A and type B, serotonin receptor 5-HT(1B...

  17. Comparable investigation in dopamine transporters with 99mTc-TRODAT-1 and 131I-FP-CIT SPECT in Parkinson's disease patients

    Institute of Scientific and Technical Information of China (English)

    LIU Congjin; LIU Xingdang; ZHANG Guangming; LI Ding; WANG Jian; YANG Liqin; JIANG Yuping

    2007-01-01

    Dopamine transporter (DAT) mediates the regulation of dopaminergic function. Two agents of TRODAT-1and FP-CIT were observed in evaluating DAT change of Parkinson's disease (PD). The relationship between them was also evaluated. The results suggested that 99mTc-TRODAT-1 SPECT and 131I-FP-CIT SPECT may serve as sensitiveand objective in vivo markers to reflect the severity of PD. The 99mTc-TRODAT-1 image is more accurate and clearercompared with 131I-FP-CIT.

  18. Evaluation of Multiple System Atrophy and Early Parkinson's Disease Using {sup 123}I-FP-CIT SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Oh, So Won; Kim, Yu Kyeong; Lee, Byung Chul; Kim, Bom Sahn; Kim, Ji Sun; Kim, Jong Min; Kim, Sang Eun [Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of)

    2009-02-15

    We investigated quantification of dopaminergic transporter (DAT) and serotonergic transporter (SERT) on {sup 123}I-FP-CIT SPECT for differentiating between multiple systemic atrophy (MSA) and idiopathic Parkinson's disease (IPD). N.fluoropropyl-2{beta}-carbomethoxy-3{beta}-4-[{sup 123}I]-iodophenylnortropane SPECT ({sup 123}I-FP-CIT SPECT) was performed in 8 patients with MSA (mean age: 64.0{+-}4.5yrs, m:f=6:2), 13 with early IPD (mean age: 65.5{+-}5.3yrs, m:f=9:4), and 12 healthy controls (mean age: 63.3{+-}5.7yrs, m:f=8:4). Standard regions of interests (ROIs) of striatum to evaluate DAT, and hypothalamus and midbrain for SERT were drawn on standard template images and applied to each image taken 4 hours after radiotracer injection. Striatal specific binding for DAT and hypothalamic and midbrain specific binding for SERT were calculated using region/reference ratio based on the transient equilibrium method. Group differences were tested using ANOVA with the postHoc analysis. DAT in the whole striatum and striatal subregions were significantly decreased in both patient groups with MSA and early IPD, compared with healthy control (p<0.05 in all). In early IPD, a significant increase in the uptake ratio in anterior and posterior putamen and a trend of increase in caudate to putamen ratio was observed. In MSA, the decrease of DAT was accompanied with no difference in the striatal uptake pattern compared with healthy controls. Regarding the brain regions where {sup 123}I-FP-CIT binding was predominant by SERT, MSA patients showed a decrease in the binding of {sup 123}I-FP-CIT in the pons compared with controls as well as early IPD patients (MSA: 0.22{+-}0.1 healthy controls: 0.33{+-}0.19, IPD: 0.29{+-}0.19), however, it did not reach the statistical significance. In this study, the differential patterns in the reduction of DAT in the striatum and the reduction of pontine {sup 123}I- FP-CIT binding predominant by SERT could be observed in MSA patients on {sup 123

  19. Human biodistribution and dosimetry of [{sup 123}I]FP-CIT: a potent radioligand for imaging of dopamine transporters

    Energy Technology Data Exchange (ETDEWEB)

    Booij, J.; Busemann Sokole, E.; De Bruin, K.; Van Royen, E.A. [Graduate School of Neurosciences, Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Stabin, M.G. [Radiation Internal Dose Information Center, Oak Ridge Institute for Science and Education, Oak Ridge, Tennessee (United States); Janssen, A.G.M. [Amersham Cygne and Eindhoven University of Technology, Eindhoven (Netherlands)

    1998-01-01

    This study reports on the biodistribution and radiation dosimetry of iodine-123-labelled N-{omega}-(flu- oropropyl)-2{beta}-carbomethoxy-3{beta}-(4-iodophenyl)tropane ([{sup 123}I]FP-CIT), a promising radioligand for the imaging of dopamine transporters. In 12 healthy volunteers, conjugate whole-body scans were performed up to 48 h following intravenous injection of approximately 100 MBq [{sup 123}I]FP-CIT. Attenuation correction was performed using a transmission whole-body scan obtained prior to injection of the radioligand, employing a {sup 123}I flood source. Blood samples were taken and urine was freely collected up to 48 h after injection of the radiotracer. For each subject, the percentage of injected activity measured in regions of interest over brain, striatum, lungs and liver were fitted to a multicompartmental model to give time-activity curves. The cumulative urine activity curve was used to model the urinary excretion rate and, indirectly, to predict faecal excretion. Using the MIRD method, nine source organs were considered in estimating absorbed radiation doses for organs of the body. The images showed rapid lung uptake and hepatobiliary excretion. Diffuse uptake and retention of activity was seen in the brain, especially in the striatum. At 48 h following the injection of [{sup 123}I]FP-CIT, mean measured urine excretion was 60%{+-}9% (SD), and mean predicted excretion in faeces was 14%{+-}1%. In general, the striatum received the highest absorbed dose (average 0.23 mGy/MBq), followed by the urinary bladder wall (average 0.054 mGy/MBq) and lungs (average 0.043 mGy/MBq). The average effective dose equivalent of [{sup 123}I]FP-CIT was estimated to be 0.024 mSv/MBq. The amount of [{sup 123}I]FP-CIT required for adequate dopamine transporter imaging results in an acceptable effective dose equivalent to the patient. (orig.) With 3 figs., 4 tabs., 39 refs.

  20. An FP7 "Space" project: Aphorism "Advanced PRocedures for volcanic and Seismic Monitoring"

    Science.gov (United States)

    Di Iorio, A., Sr.; Stramondo, S.; Bignami, C.; Corradini, S.; Merucci, L.

    2014-12-01

    APHORISM project proposes the development and testing of two new methods to combine Earth Observation satellite data from different sensors, and ground data. The aim is to demonstrate that this two types of data, appropriately managed and integrated, can provide new improved GMES products useful for seismic and volcanic crisis management. The first method, APE - A Priori information for Earthquake damage mapping, concerns the generation of maps to address the detection and estimate of damage caused by a seism. The use of satellite data to investigate earthquake damages is not an innovative issue. We can find a wide literature and projects concerning such issue, but usually the approach is only based on change detection techniques and classifications algorithms. The novelty of APE relies on the exploitation of a priori information derived by InSAR time series to measure surface movements, shake maps obtained from seismological data, and vulnerability information. This a priori information is then integrated with change detection map to improve accuracy and to limit false alarms. The second method deals with volcanic crisis management. The method, MACE - Multi-platform volcanic Ash Cloud Estimation, concerns the exploitation of GEO (Geosynchronous Earth Orbit) sensor platform, LEO (Low Earth Orbit) satellite sensors and ground measures to improve the ash detection and retrieval and to characterize the volcanic ash clouds. The basic idea of MACE consists of an improvement of volcanic ash retrievals at the space-time scale by using both the LEO and GEO estimations and in-situ data. Indeed the standard ash thermal infrared retrieval is integrated with data coming from a wider spectral range from visible to microwave. The ash detection is also extended in case of cloudy atmosphere or steam plumes. APE and MACE methods have been defined in order to provide products oriented toward the next ESA Sentinels satellite missions.The project is funded under the European Union FP7

  1. Femtosecond study of light-induced fluorescence increase of the dark chromoprotein asFP595

    Energy Technology Data Exchange (ETDEWEB)

    Schuettrigkeit, Tanja A. [Department Chemie, Technische Universitaet Muenchen, 85747 Garching (Germany); Feilitzsch, Till von [Department Chemie, Technische Universitaet Muenchen, 85747 Garching (Germany); Kompa, Christian K. [Department Chemie, Technische Universitaet Muenchen, 85747 Garching (Germany); Lukyanov, Konstantin A. [Shemiakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow (Russian Federation); Savitsky, Alexander P. [A.N. Bach Institute of Biochemistry, Russian Academy of Sciences, Moscow (Russian Federation); Voityuk, Alexander A. [Institucio Catalana de Recerca i Estudis Avancats (ICREA), Institute of Computational Chemistry, Universitat de Girona (Spain); Michel-Beyerle, Maria E. [Department Chemie, Technische Universitaet Muenchen, 85747 Garching (Germany)], E-mail: michel-beyerle@ch.tum.de

    2006-04-21

    Femtosecond time-resolved spectroscopy is applied to study the mechanism of the light-induced increase of fluorescence quantum yield of the initially non-fluorescent (dark) chromoprotein asFP595. Spectroscopic and kinetic characteristics of this unique fluorescence 'kindling' phenomenon are: (i) the small Stokes shift of the dark chromophore consistent with either the zwitterion or the anion; (ii) the singlet excited state of the dark chromophore decaying predominantly with a time constant of {approx}320 fs corresponding to a fluorescence quantum yield {phi} {sub Fl} {<=} 10{sup -4}. Since ground state recovery occurs on the same time scale, this radiationless channel is assigned to internal conversion; (iii) the formation of the fluorescent species depending on the sequential absorption of two photons with a delay significantly exceeding the excitation pulse duration of 150 fs; (iv) the fluorescent species showing a red-shift of {approx}20 nm in absorption and emission, and an excited state lifetime of 2.2 ns. The ultrafast internal conversion of the excited dark state is attributed to the proximity of the S{sub 0} and S{sub 1} potential energy surfaces favored by the non-planarity of the chromophore as revealed in recent X-ray structures. Competing with internal conversion two different transformations of the chromophore structure are suggested which may be identified in a future X-ray structural analysis of the the photoconverted fluorescent state. The predominant kindling mechanism may be either (i) trans-cis isomerization or (ii) proton transfer between an excited zwitterion and the protein cleft. For mechanism (ii) the large dipole moment change of about 11 D upon S{sub 0}-S{sub 1} excitation of the chromophore would be crucial in order to initiate protein relaxation and deprotonation of a zwitterion. Both mechanisms are assumed to lead to a metastable planar structure responsible for the long-lived fluorescence of the chromophore &apos

  2. A quantitiative LC-MS/MS method for the measurement of arachidonic acid, prostanoids, endocannabinoids, N-acylethanolamines and steroids in human plasma.

    Science.gov (United States)

    Gachet, María Salomé; Rhyn, Peter; Bosch, Oliver G; Quednow, Boris B; Gertsch, Jürg

    2015-01-22

    Free arachidonic acid is functionally interlinked with different lipid signaling networks including those involving prostanoid pathways, the endocannabinoid system, N-acylethanolamines, as well as steroids. A sensitive and specific LC-MS/MS method for the quantification of arachidonic acid, prostaglandin E2, thromboxane B2, anandamide, 2-arachidonoylglycerol, noladin ether, lineoyl ethanolamide, oleoyl ethanolamide, palmitoyl ethanolamide, steroyl ethanolamide, aldosterone, cortisol, dehydroepiandrosterone, progesterone, and testosterone in human plasma was developed and validated. Analytes were extracted using acetonitrile precipitation followed by solid phase extraction. Separations were performed by UFLC using a C18 column and analyzed on a triple quadrupole MS with electron spray ionization. Analytes were run first in negative mode and, subsequently, in positive mode in two independent LC-MS/MS runs. For each analyte, two MRM transitions were collected in order to confirm identity. All analytes showed good linearity over the investigated concentration range (r>0.98). Validated LLOQs ranged from 0.1 to 190ng/mL and LODs ranged from 0.04 to 12.3ng/mL. Our data show that this LC-MS/MS method is suitable for the quantification of a diverse set of bioactive lipids in plasma from human donors (n=32). The determined plasma levels are in agreement with the literature, thus providing a versatile method to explore pathophysiological processes in which changes of these lipids are implicated.

  3. l-Citrulline ameliorates cerebral blood flow during cortical spreading depression in rats: Involvement of nitric oxide- and prostanoids-mediated pathway.

    Science.gov (United States)

    Kurauchi, Yuki; Mokudai, Koichi; Mori, Asami; Sakamoto, Kenji; Nakahara, Tsutomu; Morita, Masahiko; Kamimura, Ayako; Ishii, Kunio

    2017-02-17

    l-Citrulline is a potent precursor of l-arginine, and exerts beneficial effect on cardiovascular system via nitric oxide (NO) production. Migraine is one of the most popular neurovascular disorder, and imbalance of cerebral blood flow (CBF) observed in cortical spreading depression (CSD) contributes to the mechanism of migraine aura. Here, we investigated the effect of l-citrulline on cardiovascular changes to KCl-induced CSD. in rats. Intravenous injection of l-citrulline prevented the decrease in CBF, monitored by laser Doppler flowmetry, without affecting mean arterial pressure and heart rate during CSD. Moreover, l-citrulline attenuated propagation velocity of CSD induced by KCl. The effect of l-citrulline on CBF change was prevented by l-NAME, an inhibitor of NO synthase, but not by indomethacin, an inhibitor of cyclooxygenase. On the other hand, attenuation effect of l-citrulline on CSD propagation velocity was prevented not only by l-NAME but also by indomethacin. In addition, propagation velocity of CSD was attenuated by intravenous injection of NOR3, a NO donor, which was diminished by ODQ, an inhibitor of soluble guanylyl cyclase. These results suggest that NO/cyclic GMP- and prostanoids-mediated pathway differently contribute to the effect of l-citrulline on the maintenance of CBF.

  4. Novel Alexa Fluor-488 labeled antagonist of the A(2A) adenosine receptor: Application to a fluorescence polarization-based receptor binding assay.

    Science.gov (United States)

    Kecskés, Miklós; Kumar, T Santhosh; Yoo, Lena; Gao, Zhan-Guo; Jacobson, Kenneth A

    2010-08-15

    Fluorescence polarization (FP) assay has many advantages over the traditional radioreceptor binding studies. We developed an A(2A) adenosine receptor (AR) FP assay using a newly synthesized fluorescent antagonist of the A(2A)AR (MRS5346), a pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine derivative conjugated to the fluorescent dye Alexa Fluor-488. MRS5346 displayed a K(i) value of 111+/-16nM in radioligand binding using [(3)H]CGS21680 and membranes prepared from HEK293 cells stably expressing the human A(2A)AR. In a cyclic AMP functional assay, MRS5346 was shown to be an A(2A)AR antagonist. MRS5346 did not show any effect on A(1) and A(3) ARs in binding or the A(2B)AR in a cyclic AMP assay at 10microM. Its suitability as a fluorescent tracer was indicated in an initial observation of an FP signal following A(2A)AR binding. The FP signal was optimal with 20nM MRS5346 and 150microg protein/mL HEK293 membranes. The association and dissociation kinetic parameters were readily determined using this FP assay. The K(d) value of MRS5346 calculated from kinetic parameters was 16.5+/-4.7nM. In FP competition binding experiments using MRS5346 as a tracer, K(i) values of known AR agonists and antagonists consistently agreed with K(i) values from radioligand binding. Thus, this FP assay, which eliminates using radioisotopes, appears to be appropriate for both routine receptor binding and high-throughput screening with respect to speed of analysis, displaceable signal and precision. The approach used in the present study could be generally applicable to other GPCRs.

  5. Construction of expression vector and transformation of FpDREB2A gene into Robinia pseudoacacia 'Idaho' mediated with Agrobacterium tumefaciens

    Institute of Scientific and Technical Information of China (English)

    Zeng Hui-ming; Wang Hua-fang

    2006-01-01

    The transcription factor gene FpDREB2A of Fraxinus pennsylvanica Marsh var. subintegerrima (Vahl.) Fern was conmefaciens GV3101. Callus was screened with G418. Morphogenesis of shoots and roots of Idaho locust transformed genes was carried out on antibiotic media. The transformed plants were verified by PCR and Southern blotting tests that the FpDREB2A gene had been inserted into the genome DNA of Idaho locust.

  6. Non-polio enteroviruses associated with acute flaccid paralysis (AFP) and facial paralysis (FP) cases in Romania, 2001-2008.

    Science.gov (United States)

    Persu, Ana; Băicuş, Anda; Stavri, Simona; Combiescu, Mariana

    2009-01-01

    Acute flaccid paralysis is a complex clinical syndrome, with a wide variety of possible etiologies and with clinical manifestations that can vary according to age or geographical region. Enteroviruses (polioviruses and non-polio enteroviruses) are among the viral agents that can cause AFP. AFP surveillance is important for public health through its use in monitoring poliomyelitis, in the context of the Global Initiative to eradicate this disease. The current paper aims to assess the non-polio enteroviruses (NPEV) association with AFP and FP cases registered in Romania in the period 2001-2008 and to identify prevalent serotypes. Within the framework of Surveillance of AFP Cases Program, were collected samples from 579 children with AFP or FP (3.069 samples). The samples were processed and inoculated onto two types of cell culture (RD and L20B), according to WHO protocol. The identification of isolated viruses has been done by the reaction of seroneutralization with pools of specific antiserum and then with monospecific antiserum for confirmation. NPEV were isolated from 58 cases (123 positive samples). During the analyzed period, 23 NPEV serotypes have circulated (15 Echo serotypes and 8 coxsackie serotypes). The most frequently identified were the Echoviruses 13 and 11 and the coxsackie A viruses. 88% of positive cases have occurred in children between 1 and 5 years. As seasonal distribution, the peak of NPEV circulation was in the months August-September (36.2%). The paper provides information about NPEV circulation in Romania in the past 8 years, about its association with the AFP and FP and it indicates the need for monitoring NPEV circulation even after the eradication of poliomyelitis.

  7. Influence of CT-based attenuation correction on dopamine transporter SPECT with [(123)I]FP-CIT.

    Science.gov (United States)

    Lapa, Constantin; Spehl, Timo S; Brumberg, Joachim; Isaias, Ioannis U; Schlögl, Susanne; Lassmann, Michael; Herrmann, Ken; Meyer, Philipp T

    2015-01-01

    Dopamine transporter (DAT) imaging using single-photon emission computed tomography (SPECT) and (123)I-labelled radiopharmaceuticals like [(123)I]FP-CIT is an established part in the diagnostic work-up of parkinsonism. Guidelines recommend attenuation correction (AC), either by a calculated uniform attenuation matrix (calAC) or by a measured attenuation map (nowadays done by low-dose CT; CTAC). We explored the impact of CTAC compared to conventional calAC on diagnostic accuracy and the use of DAT availability as a biomarker of nigrostriatal integrity.Integrated SPECT/CT studies with [(123)I]FP-CIT were performed in patients with Parkinson's disease (PD; n = 15) and essential tremor (ET; n = 15). SPECT data was reconstructed with calAC, CTAC and without AC (noAC). Regional DAT availability was assessed by uniform volume-of-interest analyses providing striatal binding potential (BP ND) estimates. BP ND values were compared among methods and correlated with clinical parameters. Compared to calAC, both CTAC and noAC provided significantly lower, but highly linearly correlated BP ND estimates (R (2) = 0.96). Diagnostic performance to distinguish between patients with PD and those with ET was very high and did not differ between AC methods. CTAC and noAC data tended so show a stronger correlation with severity and duration of disease in PD and age in ET than did calAC. Defining the reference region on low-dose CT instead of SPECT did not consistently alter findings. [(123)I]FP-CIT SPECT provides a very high diagnostic accuracy for differentiation between PD and ET that is not dependent on the employed AC method. Preliminary correlations analyses suggest that BP ND estimates derived from CTAC represent a superior biomarker of nigrostriatal integrity.

  8. Differential Diagnosis of Patients with Inconclusive Parkinsonian Features Using [{sup 18}F]FP-CIT PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Park, Eunkyung; Hwang, Yu Mi; Lee, Channyoung; Oh, Sun Young; Kim, Young Chul; Choe, Jae Gol; Park, Kun Woo [Korea Univ., Seoul (Korea, Republic of); Kim, Sujin [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2014-06-15

    It is often difficult to differentiate parkinsonism, especially when patients show uncertain parkinsonian features. We investigated the usefulness of dopamine transporter (DAT) imaging for the differential diagnosis of inconclusive parkinsonism using [{sup 18}F]FP-CIT PET. Twenty-four patients with inconclusive parkinsonian features at initial clinical evaluation and nine healthy controls were studied. Patients consisted of three subgroups: nine patients whose diagnoses were unclear concerning whether they had idiopathic Parkinson's disease or drug-induced parkinsonism ('PD/DIP'), nine patients who fulfilled neither the diagnostic criteria of PD nor of essential tremor ('PD/ET'), and six patients who were alleged to have either PD or atypical parkinsonian syndrome ('PD/APS'). Brain PET images were obtained 120 min after injection of 185 MBq [{sup 18}F]FP-CIT. Imaging results were quantified and compared with follow-up clinical diagnoses. Overall, 11 of 24 patients demonstrated abnormally decreased DAT availability on the PET scans, whereas 13 were normal. PET results could diagnose PD/DIP and PD/ET patients as having PD in six patients, DIP in seven, and ET in five; however, the diagnoses of all six PD/APS patients remained inconclusive. Among 15 patients who obtained a final follow-up diagnosis, the image-based diagnosis was congruent with the follow-up diagnosis in 11 patients. Four unsolved cases had normal DAT availability, but clinically progressed to PD during the follow-up period. [{sup 18}F]FP-CIT PET imaging is useful in the differential diagnosis of patients with inconclusive parkinsonian features, except in patients who show atypical features or who eventually progress to PD.

  9. {sup 123}I-FP-CIT SPECT findings and its clinical relevance in prodromal dementia with Lewy bodies

    Energy Technology Data Exchange (ETDEWEB)

    Kasanuki, Koji [Juntendo University School of Medicine, PET/CT Dementia Research Center, Juntendo Tokyo Koto Geriatric Medical Center, Tokyo (Japan); Juntendo University School of Medicine, Department of Psychiatry, Tokyo (Japan); Mayo Clinic, Department of Neuroscience, Jacksonville, FL (United States); Iseki, Eizo; Ota, Kazumi [Juntendo University School of Medicine, PET/CT Dementia Research Center, Juntendo Tokyo Koto Geriatric Medical Center, Tokyo (Japan); Juntendo University School of Medicine, Department of Psychiatry, Tokyo (Japan); Kondo, Daizo; Sato, Kiyoshi [Juntendo University School of Medicine, PET/CT Dementia Research Center, Juntendo Tokyo Koto Geriatric Medical Center, Tokyo (Japan); Ichimiya, Yosuke; Arai, Heii [Juntendo University School of Medicine, Department of Psychiatry, Tokyo (Japan)

    2017-03-15

    Evidence for the prodromal stage of dementia with Lewy bodies (DLB) is very limited. To address this issue, we investigate the {sup 123}I-FP-CIT SPECT measure of dopamine transporter binding finding and its clinical relevance. We enrolled subjects into a prodromal DLB group (PRD-DLB) (n = 20) and clinical DLB group (CLIN-DLB) (n = 18) and compared these groups with an Alzheimer's disease control group (AD) (n = 10). PRD-DLB was defined as patients having the non-motor symptoms associated with Lewy body disease (LBD) [i.e. REM sleep behavior disorder (RBD), olfactory dysfunction, autonomic dysfunction, and depression] and showing characteristic diffuse occipital hypometabolism in {sup 18}F-FDG PET. CLIN-DLB was defined as patients fulfilling the established criteria of probable DLB. Striatal specific binding ratio (SBR) of {sup 123}I-FP-CIT SPECT was used for objective group comparisons. The correlations between SBR and cognitive function (MMSE), motor symptoms (UPDRS3), and duration of LBD-associated non-motor symptoms were compared between the two DLB groups. Mean SBR scores of both PRD-DLB and CLIN-DLB were significantly lower than those of AD. No correlation was found between SBR and MMSE scores. Both in the CLIN-DLB and total DLB groups, SBR scores were negatively correlated with UPDRS3 scores, whereas no correlation was found in PRD-DLB. Among the LBD-related non-motor symptoms, duration of olfactory dysfunction, and RBD demonstrated negative correlation with SBR scores in PRD-DLB. {sup 123}I-FP-CIT SPECT may play a role for detecting DLB among the subjects in prodromal stage. During this stage, long-term olfactory dysfunction and/or RBD may indicate more severe degeneration of the nigro-striatal dopaminergic pathway. (orig.)

  10. Photon and decay data libraries for ORIGEN2 code based on JENDL FP decay data file 2000

    Energy Technology Data Exchange (ETDEWEB)

    Katakura, Jun-ichi; Yanagisawa, Hiroshi [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    2002-11-01

    Photon and decay data libraries for the ORIGEN2 code have been updated by using JENDL FP Decay Data File 2000 (JENDL/FPD-00). As for the decay data, half-lives, branching ratios and recoverable energy values have been replaced with those of the JENDL/FPD-00 file. The data of the photon library has been also replaced with those of the JENDL/FPD-00 file in which photon data of the nuclides without measured data are calculated with a theoretical method. Using the updated photon library, the calculation of photon spectrum at a short time after fission event is able to be made. (author)

  11. Silicon-Light: a European FP7 Project Aiming at High Efficiency Thin Film Silicon Solar Cells on Foil

    DEFF Research Database (Denmark)

    Soppe, W.; Haug, F.-J.; Couty, P.

    2011-01-01

    Silicon-Light is a European FP7 project, which started January 1st, 2010 and aims at development of low cost, high-efficiency thin film silicon solar cells on foil. Three main routes are explored to achieve these goals: a) advanced light trapping by implementing nanotexturization through UV Nano...... Imprinting Lithography (UV-NIL); b) growth of crack-free silicon absorber layers on highly textured substrates; c) development of new TCOs which should combine the best properties of presently available materials like ITO and AZO. The paper presents the midterm status of the project results, showing model...

  12. Influence of CT-based attenuation correction on dopamine transporter SPECT with [123I]FP-CIT

    OpenAIRE

    Lapa, Constantin; Spehl, Timo S; Brumberg, Joachim; Isaias, Ioannis U; Schlögl, Susanne; Lassmann, Michael; Herrmann, Ken; Philipp T. Meyer

    2015-01-01

    Dopamine transporter (DAT) imaging using single-photon emission computed tomography (SPECT) and 123I-labelled radiopharmaceuticals like [123I]FP-CIT is an established part in the diagnostic work-up of parkinsonism. Guidelines recommend attenuation correction (AC), either by a calculated uniform attenuation matrix (calAC) or by a measured attenuation map (nowadays done by low-dose CT; CTAC). We explored the impact of CTAC compared to conventional calAC on diagnostic accuracy and the use of DAT...

  13. Intermediate-energy inverse-kinematics one-proton pickup reactions on neutron-deficient $fp$-shell nuclei

    CERN Document Server

    McDaniel, S; Tostevin, J A; Baugher, T; Bazin, D; Brown, B A; Cook, J M; Glasmacher, T; Grinyer, G F; Ratkiewicz, A; Weisshaar, D

    2012-01-01

    Background: Thick-target-induced nucleon-adding transfer reactions onto energetic rare-isotope beams are an emerging spectroscopic tool. Their sensitivity to single-particle structure complements one-nucleon removal reaction capabilities in the quest to reveal the evolution of nuclear shell structure in very exotic nuclei. Purpose: To add intermediate-energy, carbon-target-induced one-proton pickup reactions to the arsenal of $\\gamma$-ray tagged direct reactions applicable in the regime of low beam intensities and to apply these for the first time to $fp$-shell nuclei. Methods: Inclusive and partial cross sections were measured for the $\

  14. Photon and decay data libraries for ORIGEN2 code based on JENDL FP decay data file 2000

    CERN Document Server

    Katakura, J I

    2002-01-01

    Photon and decay data libraries for the ORIGEN2 code have been updated by using JENDL FP Decay Data File 2000 (JENDL/FPD-00). As for the decay data, half-lives, branching ratios and recoverable energy values have been replaced with those of the JENDL/FPD-00 file. The data of the photon library has been also replaced with those of the JENDL/FPD-00 file in which photon data of the nuclides without measured data are calculated with a theoretical method. Using the updated photon library, the calculation of photon spectrum at a short time after fission event is able to be made.

  15. Silicon-Light: a European FP7 Project Aiming at High Efficiency Thin Film Silicon Solar Cells on Foil

    DEFF Research Database (Denmark)

    Soppe, W.; Haug, F.-J.; Couty, P.

    2011-01-01

    Silicon-Light is a European FP7 project, which started January 1st, 2010 and aims at development of low cost, high-efficiency thin film silicon solar cells on foil. Three main routes are explored to achieve these goals: a) advanced light trapping by implementing nanotexturization through UV Nano...... calculations of ideal nanotextures for light trapping in thin film silicon solar cells; the fabrication of masters and the replication and roll-to-roll fabrication of these nanotextures. Further, results on ITO variants with improved work function are presented. Finally, the status of cell fabrication on foils...

  16. CSIR and its activities in the European Union's (EU) framework programmes (FPs): special focus on FP6

    CSIR Research Space (South Africa)

    Meese, G

    2006-02-01

    Full Text Available the CSIR has been the most successful science and technology organisation in South Africa in FP6 and is involved in the following projects: Project acronym Title Theme Co-ordinator Web site Pharma-Planta** Recombinant pharmaceuticals from plants...-Novem, The Netherlands Under development Project acronym Title Theme Co-ordinator Web site BESTUFS Best urban freight solutions 6 NEA Transport Research and Training, The Netherlands www.bestufs.net CSIR acts as a subcontractor SIMBA Strengthening road transport...

  17. Scientific Opinion on the Pest Risk Analysis on Phytophthora ramorum prepared by the FP6 project RAPRA

    DEFF Research Database (Denmark)

    Baker, R.; Candresse, T.; Dormannsné Simon, E.

    2011-01-01

    The Panel on Plant Health was asked to deliver a scientific opinion on the Pest Risk Analysis on Phytophthora ramorum prepared by the FP6 project RAPRA, taking into account comments by Member States and additional information since RAPRA. P. ramorum is the oomycete causing sudden oak death...... is a risk of further entry (of known or new lineages and/or mating types), establishment and […] impact”. It is advisable to avoid introductions of different lineages because of inherent phenotypic differences and the potential for sexual recombination. The Panel supports the management options proposed...

  18. A New Method to Extract Customer Relational Graph Based on Modified FP-Growth Algorithm%基于改进的FP-Growth算法提取客户关系图

    Institute of Scientific and Technical Information of China (English)

    汪欢文; 陆海良; 单宇翔

    2015-01-01

    利用客户关系图可以很清晰地看出企业与客户之间的各类关系,便于企业决策者采取针对性的措施来改善客户关系.该文提出了一种基于改进的FP-Growth算法进行客户关系图提取的方法,通过最小支持度寻找到所有的频繁项集,然后结合最小置信度,筛选出所需要的关联规则来提高算法的效率.本方法已应用于浙江中烟CRM系统,结果证明该改进算法有比较好的效果.%Customer relationships can be clearly seen in customer relationship graph, thus business decision-makers can take spe-cific measures to facilitate customer relationships. This paper presents an improved algorithm based on FP-Growth algorithm to ex-tract customer relationship graph. We find all frequent itemsets through minimum support, then filter out the desired association rules integrated with the minimum confidence, which can improve the efficiency of the algorithm considerably. This method has been applied to Zhejiang Tobacco CRM system, and the results show that the improved algorithm is very effective.

  19. Gr-凝聚环的小有限分次投射维数gr.fp.dimR%Small Finite Graded Projective Dimension gr. fp. dimR of Gr - Coherent Rings

    Institute of Scientific and Technical Information of China (English)

    赵巨涛

    2002-01-01

    文[1],[2]分别研究了Gr-Norether Gr-局部(半局部)环的同调维数,文章主要进一步讨论Gr-凝聚Gr-半局部环的同调性质.在§1中,主要刻画交换Gr-凝聚Gr-半局部环R的分次弱整体维数gr.gl.w.dimR;在§2中,定义了分次环R的小有限分次投射维数gr.fp.dimR.刻画了gr.fp.dimR=gr.gl. w.dimR的Gr-凝聚环.由于Gr-Norether环是Gr-凝聚的,因而本文所得的结果对于Gr-Norether环是自然成立的.同时,本文所得的结果,也可视为文[4]关于一般交换凝聚环相应结论的推广.

  20. Gr-凝聚环的小有限分次投射维数gr.fp.dimR%Small Finite Graded Projective Dimension gr.fp.dimR of Gr-Coherent Rings

    Institute of Scientific and Technical Information of China (English)

    赵巨涛; 黄寄洪

    2004-01-01

    文[1],[2]分别研究了Gr-Noether Gr-局部(半局部)环的同调维数,本文主要进一步讨论Gr-凝聚Gr-半局部环的同调性质. 在§1中,主要刻画交换Gr-凝聚Gr-半局部环R的分次弱整体维数gr.gl.w.dimR; 在§2中,定义了分次环R的小有限分次投射维数gr.fp.dimR. 刻画了gr.fp.dimR=gr.gl.w.dimR的Gr-凝聚环. 由于Gr-Noether环是Gr-凝聚的,因而本文所得的结果对于Gr-Noether环是自然成立的. 同时,本文所得的结果,也可视为文[4]关于一般交换凝聚环相应结论的推广.

  1. No significant effects of single intravenous, single oral and subchronic oral administration of acetylcholinesterase inhibitors on striatal [{sup 123}I]FP-CIT binding in rats

    Energy Technology Data Exchange (ETDEWEB)

    Knol, R.J.J.; Booij, J. [University of Amsterdam, Department of Nuclear Medicine, Academic Medical Center, Amsterdam (Netherlands); Graduate School of Neurosciences, Amsterdam (Netherlands); Bruin, K. de; Eck-Smit, B.L.F. van [University of Amsterdam, Department of Nuclear Medicine, Academic Medical Center, Amsterdam (Netherlands)

    2008-03-15

    [{sup 123}I]FP-CIT SPECT is a valuable diagnostic tool to discriminate Lewy body dementia from Alzheimer's dementia. To date, however, it is uncertain whether the frequently used acetylcholinesterase inhibitors (AChEIs) by demented patients, have an effect on [{sup 123}I]FP-CIT binding to dopamine transporters (DATs). Earlier animal studies showed a decline of DAT availability after acute intravenous injection of AChEIs. The aim of this study was to investigate effects of single intravenous, single oral and subchronic oral administration of AChEIs on DAT availability in the rat brain as measured by [{sup 123}I]FP-CIT. Biodistribution studies were performed in Wistar rats (n = 5-16 per group). Before [{sup 123}I]FP-CIT injection, rats were injected intravenously with a single dose of the AChEI rivastigmine (2.5 mg/kg body weight) or donepezil (0.5 mg/kg), the DAT-blocker methylphenidate (10 mg/kg) or saline. A second group was orally treated with a single dose of rivastigmine or donepezil (2.5 mg/kg), methylphenidate (10 mg/kg) or saline before injection of [{sup 123}I]FP-CIT. Studies were also performed in rats that were orally treated during 14 consecutive days with either rivastigmine (1 mg/kg daily), donepezil (1.5 mg/kg daily), methylphenidate (2.5 mg/kg) or saline. Brain parts were assayed in a gamma counter, and specific striatum/cerebellum ratios were calculated for the [{sup 123}I]FP-CIT binding to DATs. No significant effects of either single intravenous, single oral or subchronic oral administration of AChEIs on striatal FP-CIT binding could be detected. Single pretreatment with methylphenidate resulted in an expected significantly lower striatal FP-CIT binding. We conclude that in rats, single intravenous and single or subchronic oral administration of the tested AChEIs does not lead to an important alteration of [{sup 123}I]FP-CIT binding to striatal DATs. Therefore, it is unlikely that these drugs will induce large effects on the interpretation of

  2. The Structure of the Heavy Calcium Isotopes and the Effective Interaction in the sd-fp Shell

    CERN Multimedia

    Dorvaux, O; Nowacki, F; Courtin, S; Marechal, F; Siiskonen, T M; Perrot, F; Pietri, S B

    2002-01-01

    Nuclei with 40 $<$ A $<$ 56, near the stability line, are very well described in the frame of the shell model. However, when the number of neutrons increases, the situation becomes more complex which explains why the interaction can be found very dissimilar within different calculations. Heavy Ca isotopes, because of the simplicity of their wave-functions, correspond to the optimal choice to fix unambiguously the interaction in this mass region.\\\\ It is proposed to measure the $\\beta$-decay of $^{51, 52, 53}$K with the help of an utmost performing neutron (TONNERRE array) and $\\gamma$- (Miniball clusters) detection, allowing efficient coincidence measurements. This will allow the lowest lying Gamow-Teller states to be located in $^{51, 52, 53}$Ca, and the still unknown properties of natural parity states to be investigated. The awaited results should allow to settle the n-n interaction in the fp shell and the Gnp matrix accross the sd and fp shells, one step farther from stability, by comparison with fu...

  3. A strategy using NMR peptide structures of thromboxane A2 receptor as templates to construct ligand-recognition pocket of prostacyclin receptor

    Directory of Open Access Journals (Sweden)

    Ruan Ke-He

    2005-11-01

    Full Text Available Abstract Background: Prostacyclin receptor (IP and thromboxane A2 receptor (TP belong to rhodopsin-type G protein-coupling receptors and respectively bind to prostacyclin and thromboxane A2 derived from arachidonic acid. Recently, we have determined the extracellular loop (eLP structures of the human TP receptor by 2-D 1H NMR spectroscopy using constrained peptides mimicking the individual eLP segments. The studies have identified the segment along with several residues in the eLP domains important to ligand recognition, as well as proposed a ligand recognition pocket for the TP receptor. Results: The IP receptor shares a similar primary structure in the eLPs with those of the TP receptor. Forty percent residues in the second eLPs of the receptors are identical, which is the major region involved in forming the ligand recognition pocket in the TP receptor. Based on the high homology score, the eLP domains of the IP receptor were constructed by the homology modeling approach using the NMR structures of the TP eLPs as templates, and then configured to the seven transmembrane (TM domains model constructed using the crystal structure of the bovine rhodopsin as a template. A NMR structure of iloprost was docked into the modeled IP ligand recognition pocket. After dynamic studies, the segments and residues involved in the IP ligand recognition were proposed. A key residue, Arg173 involved in the ligand recognition for the IP receptor, as predicted from the modeling, was confirmed by site-directed mutagenesis. Conclusion: A 3-D model of the human IP receptor was constructed by homology modeling using the crystal structure of bovine rhodopsin TM domains and the NMR structures of the synthetic constrained peptides of the eLP domains of the TP receptor as templates. This strategy can be applied to molecular modeling and the prediction of ligand recognition pockets for other prostanoid receptors.

  4. [Clinical evaluations of neoadjuvant chemotherapy with DN and FP regimens for patients with middle or lower thoracic locally advanced esophageal squamous cell carcinoma].

    Science.gov (United States)

    Yang, Hongxia; Yao, Juan; Wen, Hong; Yu, Lan; Liu, Wu; Liang, Hua; Han, Shuhong

    2015-05-19

    To explore the efficacies and side effects of neoadjuvant chemotherapy with DN (docetaxel plus cisplatin) and FP (nedaplatin plus cisplatin) regimens for patients with upper or middle thoracic locally advanced esophageal squamous cell carcinoma. From January 2008 to January 2012, a total of 124 patients with upper or middle thoracic locally advanced esophageal squamous cell carcinoma were randomized into DN group (n = 64) and FP group (n = 60). Both groups received neoadjuvant chemotherapy. The treatment schedule was recycled every 3 weeks. After 2 cycles, those with potential surgical resection underwent surgery. The 2-year overall, locoregional relapse-free and distant metastasis-free survival rates in DN and FP groups were 71.1% and 66.7%, 65.0% and 63.0%, 78.3% and 74.3% respectively (P > 0.05). The incidence of leucopenia was higher in DN group than that in FP group (P DN group. No perioperative mortality occurred with a low incidence of postoperative complications. The rates of overall response, resection, postoperative complications and pathological complete rates response were similar in two groups. And the rates of downstage and R0 resection were significantly higher in DN group than those in FP group (P < 0.05). For patients with middle or lower thoracic locally advanced esophageal squamous cell carcinoma, neoadjuvant chemotherapies of docetaxel and nedaplatin may achieve excellent outcomes in clinical response and 2-year survival rate. And the side effects are clinically acceptable.

  5. Expression of prostaglandin receptors in Chlamydia trachomatis-infected recurrent spontaneous aborters.

    Science.gov (United States)

    Singh, Namita; Prasad, Priya; Singh, Laishram Chandreshwar; Das, Banashree; Rastogi, Sangita

    2016-06-01

    A study was undertaken to quantify the expression of prostaglandin (PG) receptors and find the effect of gestational age on expression of PG receptor genes in Chlamydia trachomatis-infected recurrent spontaneous aborters (RSA). Endometrial curettage tissue (ECT) was collected from 130 RSA (Group I) and 100 age-matched controls (Group II) at the Department of Obstetrics and Gynecology, Safdarjung Hospital, New Delhi (India). PCR was performed for diagnosis of C. trachomatis cryptic plasmid; mRNA expression of PG receptor genes was assessed by real-time PCR (q-PCR), while serum progesterone/estrogen levels were determined by respective commercial kits. Data were evaluated statistically. A total of 15.4 % RSA (GroupI) were diagnosed as C. trachomatis-positive (200 bp), whereas controls were uninfected. q-PCR showed significant upregulation (PPGE2 (EP-1, EP-2, EP-3, EP-4), PGF2α (FP) and PGI2 (IP) receptors in Group I versus Group II. The expression of PG receptors increased significantly with advanced gestational age (Preceptors, EP-1, EP-3 and FP, were positively correlated with gestational age in Group-I. In infected RSA, mean serum progesterone level was significantly low (Pexpression of PG receptors, particularly contractile gene receptors (EP-1, EP-3, FP), with advanced gestational age and altered steroid levels could be a possible risk factor for abortion in Chlamydia-infected RSA.

  6. Dopaminergic dysfunction and psychiatric symptoms in movement disorders: a {sup 123}I-FP-CIT SPECT study

    Energy Technology Data Exchange (ETDEWEB)

    Di Giuda, Daniela; Cocciolillo, Fabrizio; Bruno, Isabella; Giordano, Alessandro [Universita Cattolica del Sacro Cuore, Istituto di Medicina Nucleare, Rome (Italy); Camardese, Giovanni; Pucci, Lorella; Janiri, Luigi [Universita Cattolica del Sacro Cuore, Istituto di Psichiatria e Psicologia, Rome (Italy); Bentivoglio, Anna Rita; Guidubaldi, Arianna [Universita Cattolica del Sacro Cuore, Istituto di Neurologia, Rome (Italy); Fasano, Alfonso [Universita Cattolica del Sacro Cuore, Istituto di Neurologia, Rome (Italy); AFaR-Associazione Fatebenefratelli per la Ricerca, Rome (Italy)

    2012-12-15

    Psychiatric symptoms frequently occur in patients with movement disorders. They are not a mere reaction to chronic disability, but most likely due to a combination of psychosocial factors and biochemical dysfunction underlying the movement disorder. We assessed dopamine transporter (DAT) availability by means of {sup 123}I-FP-CIT SPECT, and motor and psychiatric features in patients with Parkinson's disease, primary dystonia and essential tremor, exploring the association between SPECT findings and symptom severity. Enrolled in the study were 21 patients with Parkinson's disease, 14 patients with primary dystonia and 15 patients with essential tremor. The severity of depression symptoms was assessed using the Hamilton depression rating scale, anxiety levels using the Hamilton anxiety rating scale and hedonic tone impairment using the Snaith-Hamilton pleasure scale. Specific {sup 123}I-FP-CIT binding in the caudate and putamen was calculated based on ROI analysis. The control group included 17 healthy subjects. As expected, DAT availability was significantly decreased in patients with Parkinson's disease, whereas in essential tremor and dystonia patients it did not differ from that observed in the control group. In Parkinson's disease patients, an inverse correlation between severity of depression symptoms and DAT availability in the left caudate was found (r = -0.63, p = 0.002). In essential tremor patients, levels of anxiety symptoms were inversely correlated with DAT availability in the left caudate (r = -0.69, p = 0.004). In dystonia patients, the severities of both anxiety and depression symptoms were inversely associated with DAT availability in the left putamen (r = -0.71, p = 0.004, and r = -0.75, p = 0.002, respectively). There were no correlations between psychometric scores and {sup 123}I-FP-CIT uptake ratios in healthy subjects. We found association between presynaptic dopaminergic function and affective symptoms in different movement

  7. Reduction in camera-specific variability in [(123)I]FP-CIT SPECT outcome measures by image reconstruction optimized for multisite settings

    DEFF Research Database (Denmark)

    Buchert, Ralph; Kluge, Andreas; Tossici-Bolt, Livia

    2016-01-01

    reconstruction algorithm for its ability to reduce camera-specific intersubject variability in [(123)I]FP-CIT SPECT. The secondary aim was to evaluate binding in whole brain (excluding striatum) as a reference for quantitative analysis. METHODS: Of 73 healthy subjects from the European Normal Control Database...... of [(123)I]FP-CIT recruited at six centres, 70 aged between 20 and 82 years were included. SPECT images were reconstructed using the QSPECT software package which provides fully automated detection of the outer contour of the head, camera-specific correction for scatter and septal penetration...... by transmission-dependent convolution subtraction, iterative OSEM reconstruction including attenuation correction, and camera-specific "to kBq/ml" calibration. LINK and HERMES reconstruction were used for head-to-head comparison. The specific striatal [(123)I]FP-CIT binding ratio (SBR) was computed using...

  8. Iloprost-induced desensitization of the prostacyclin receptor in isolated rabbit lungs

    Science.gov (United States)

    Schermuly, Ralph T; Pullamsetti, Soni S; Breitenbach, Susanne C; Weissmann, Norbert; Ghofrani, Hossein A; Grimminger, Friedrich; Nilius, Sigrid M; Schrör, Karsten; Meger-Kirchrath, Jutta; Seeger, Werner; Rose, Frank

    2007-01-01

    Background The rapid desensitization of the human prostacyclin (IP) in response to agonist binding has been shown in cell culture. Phosphorylation of the IP receptor by protein kinase C (PKC) has been suggested to be involved in this process. Methods and results In this study we investigated the vasodilatory effects of iloprost, a stable prostacyclin analogue, in perfused rabbit lungs. Continuous infusion of the thromboxane mimetic U46619 was employed to establish stable pulmonary hypertension. A complete loss of the vasodilatory response to iloprost was observed in experiments with continuous iloprost perfusion, maintaining the intravascular concentration of this prostanoid over a 180 min period. When lungs under chronic iloprost infusion were acutely challenged with inhaled iloprost, a corresponding complete loss of vasoreactivity was observed. This desensitization was not dependent on upregulation of cAMP-specific phosphodiesterases or changes in adenylate cyclase activity, as suggested by unaltered dose-response curves to agents directly affecting these enzymes. Application of a prostaglandin E1 receptor antagonist 6-isopropoxy-9-oxoxanthene-2-carboxylic acid (AH 6809) or the PKC inhibitor bisindolylmaleimide I (BIM) enhanced the vasodilatory response to infused iloprost and partially prevented tachyphylaxis. Conclusion A three-hour infusion of iloprost in pulmonary hypertensive rabbit lungs results in complete loss of the lung vasodilatory response to this prostanoid. This rapid desensitization is apparently not linked to changes in adenylate cyclase and phosphodiesterase activation, but may involve PKC function and co-stimulation of the EP1 receptor in addition to the IP receptor by this prostacyclin analogue. PMID:17257398

  9. Iloprost-induced desensitization of the prostacyclin receptor in isolated rabbit lungs

    Directory of Open Access Journals (Sweden)

    Schrör Karsten

    2007-01-01

    Full Text Available Abstract Background The rapid desensitization of the human prostacyclin (IP in response to agonist binding has been shown in cell culture. Phosphorylation of the IP receptor by protein kinase C (PKC has been suggested to be involved in this process. Methods and results In this study we investigated the vasodilatory effects of iloprost, a stable prostacyclin analogue, in perfused rabbit lungs. Continuous infusion of the thromboxane mimetic U46619 was employed to establish stable pulmonary hypertension. A complete loss of the vasodilatory response to iloprost was observed in experiments with continuous iloprost perfusion, maintaining the intravascular concentration of this prostanoid over a 180 min period. When lungs under chronic iloprost infusion were acutely challenged with inhaled iloprost, a corresponding complete loss of vasoreactivity was observed. This desensitization was not dependent on upregulation of cAMP-specific phosphodiesterases or changes in adenylate cyclase activity, as suggested by unaltered dose-response curves to agents directly affecting these enzymes. Application of a prostaglandin E1 receptor antagonist 6-isopropoxy-9-oxoxanthene-2-carboxylic acid (AH 6809 or the PKC inhibitor bisindolylmaleimide I (BIM enhanced the vasodilatory response to infused iloprost and partially prevented tachyphylaxis. Conclusion A three-hour infusion of iloprost in pulmonary hypertensive rabbit lungs results in complete loss of the lung vasodilatory response to this prostanoid. This rapid desensitization is apparently not linked to changes in adenylate cyclase and phosphodiesterase activation, but may involve PKC function and co-stimulation of the EP1 receptor in addition to the IP receptor by this prostacyclin analogue.

  10. Computational Study of Absorption Spectra of the Photoconvertible Fluorescent Protein EosFP in Different Protonation States.

    Science.gov (United States)

    Imhof, Petra

    2012-11-13

    Absorption spectra of the green-to-red convertible fluorescent protein EosFP have been computed in a hybrid quantum mechanical/molecular mechanical (QM/MM) framework. The experimentally observed absorption maximum at ∼390 nm is well reproduced by the protein with a neutral chromophore, and the anionic form is computed to absorb close to the experimentally determined maximum at ∼500 nm. Absorption of a zwitterionic form is calculated to lie in the same spectral region; however, this species cannot be unambiguously assigned to the experimental spectra. Variation of the protonation states of residues surrounding the chromophore do not have significant impact on the positions of the absorption maxima. In particular, protonation of Glu212 leaves the calculated spectra largely unaffected. This is consistent with the spectra of the E212Q mutant, which differ from the wild-type spectra only in the intensities but not in the positions of the absorption bands.

  11. Study of the electronic and magnetic properties of EuAlO{sub 3} using FP-LAPW method

    Energy Technology Data Exchange (ETDEWEB)

    Sandeep,, E-mail: sndp.chettri@gmail.com; Shankar, A.; Rai, D. P.; Thapa, R. K. [Department of Physics, Mizoram University, Aizawl, Mizoram, India, 796004 (India); Ghimire, M. P. [National Institute for Material Sciences, Tsukuba (Japan)

    2015-05-15

    The electronic and magnetic properties of EuAlO{sub 3} is calculated by first-principles full-potential linearized augmented plane wave (FP-LAPW) method based on density functional theory (DFT). Density of states (DOS), magnetic moments and band structures of the systems are presented. For the exchange and correlation energy, local spin density approximation (LSDA+U) with the inclusion of Hubbard potential U is used. Our calculation showed an indirect band gap of the order of 4 eV for EuAlO{sub 3} in the spin down channel of the DOS and band structures supporting HMF nature of the system. The effective magnetic moment of 6.00 µ{sub B} also supported the above conclusion with an integral value. The DOS of Eu were found responsible for the HMF nature of the system.

  12. Valorisation of crude glycerol through biological conversion into bioplastics and biofuels in the frame of an FP7 project

    DEFF Research Database (Denmark)

    Varrone, Cristiano; Gavala, Hariklia N.

    for 2011 was over 8.6 million metric tons, but to date an effective use for the glycerol derived from biodiesel production does not exist on the market. In fact, even though high purity glycerol can be used in the cosmetic and pharmaceutical industry, crude glycerol derived from biodiesel production has...... is the valorisation of glycerol streams generated during the biodiesel production process, using microbial mixed culture (MMC) technology. The use of bioconversion into high-value products represents a promising route to achieve economic viability in the biofuel industry. Until now there have been several studies...... of a broader European strategy, in good synergy with other on-going FP7 projects, which can contribute to achieve new solutions for a knowledge-based economy, increasing the economic viability of the biodiesel industry, and developing new international collaborations....

  13. Trojan Horse measurement of the {sup 18}F(p, α){sup 15}O astrophysical S(E)-factor

    Energy Technology Data Exchange (ETDEWEB)

    Pizzone, R.G. [Texas A and M University, Cyclotron Institute, College Station, TX (United States); INFN, Laboratori Nazionali del Sud, Catania (Italy); Roeder, B.T.; McCleskey, M. [Texas A and M University, Cyclotron Institute, College Station, TX (United States); Trache, L. [Texas A and M University, Cyclotron Institute, College Station, TX (United States); IFIN-HH, Bucharest-Magurele (Romania); Tribble, R.E. [Texas A and M University, Cyclotron Institute, College Station, TX (United States); Brookhaven National Laboratory, Upton, New York (United States); Spitaleri, C.; Indelicato, I.; Rapisarda, G.G.; Sparta, R. [INFN, Laboratori Nazionali del Sud, Catania (Italy); Universita degli Studi di Catania, Dipartimento di Fisica e Astronomia, Catania (Italy); Bertulani, C.A. [Texas A and M University-Commerce, Department of Physics and Astronomy, Commerce (United States); Cherubini, S. [INFN, Laboratori Nazionali del Sud, Catania (Italy); Brookhaven National Laboratory, Upton, New York (United States); Gulino, M. [INFN, Laboratori Nazionali del Sud, Catania (Italy); KORE University, Enna (Italy); La Cognata, M. [INFN, Laboratori Nazionali del Sud, Catania (Italy); Lamia, L. [Universita degli Studi di Catania, Dipartimento di Fisica e Astronomia, Catania (Italy)

    2016-02-15

    Crucial information on novae nucleosynthesis is linked to the abundance of {sup 18}F, which, due to great improvements in gamma-ray astronomy, can be detected in explosive environments. Therefore, the reaction network producing and destroying this radioactive isotope has been extensively studied in the last years. Among those reactions, the {sup 18}F(p, α){sup 15}O cross section has been measured by means of several dedicated experiments, both using direct and indirect methods. The presence of resonances in the energy region of astrophysical interest has been reported by many authors. In the present work a report on a recent experiment performed via the Trojan Horse Method (THM) is presented and the results are given and compared with the ones known in the literature, both direct and indirect. Data arising from THM measurements are then averaged and the reaction rate calculated in the novae energy range. (orig.)

  14. Prepulse Inhibition is Associated with Attention, Processing Speed, and 123I-FP-CIT SPECT in Parkinson's Disease

    DEFF Research Database (Denmark)

    Zoetmulder, Marielle; Biernat, Heidi B; Nikolic, Miki;

    2014-01-01

    cognitive information processing deficits such as slowed processing speed. Parkinson's disease is characterised by the degeneration of the midbrain dopaminergic system and is associated with cognitive dysfunction, including slowed information processing. Although sensorimotor processes in Parkinson......'s disease have been extensively studied in relation to motor function, less is known about the potential role of sensorimotor processes in cognitive function. Objective: We investigated the relationship between prepulse inhibition, cognition and nigrostriatal dysfunction, as measured with 123I...... performed better on cognitive measures tapping attention and processing speed than patients with a lower level of prepulse inhibition group. Furthermore, there were significant correlations between prepulse inhibition and 123I-FP-CIT uptake in the striatum. Conclusions: Our results suggest that the level...

  15. Making Use of the Latest Earth Observation Datasets from Copernicus Programme: The SAFI EU-FP7 Project

    Science.gov (United States)

    Vincent, Chloe; Mangin, Antoine; Bryere, Philippe; Serra, Romain; Sicard, Pierre; Lesne, Olivia; Scarrott, Rory; Dunne, Declan; Gault, Jeremy; Lecouffe, Catherine; Rougier, Antoine; Jarry, Etienne; Morales, Jesus; Moreno, Oscar; Duque Perea, Raquel; Jimenez, Carlos; Martinez, Ines; Gaspar, Miguel; Rufino, Marta; Santos, Miguel A.; Garrido, Susana; Bugalho, Lourdes; Marques, Vitor; Shorten, Marc; Smith, Catherine; Maguire, Julie; Amine Taji, Mohamed

    2016-08-01

    The EU-FP7 funded project SAFI ("Supporting our Aquaculture and Fisheries Industries", www.safiservices.eu) is primary focused on the exploitation of Earth Observation (EO) data resources, is specifically targeting the support of fisheries and aquaculture industries in our ocean and near-shore areas. The initiative aims at providing information assistance for marine aquaculture deployment (optimization of cage location with respect to environmental and ecological context) and environmental monitoring during operations. It also targets supporting fisheries providing informative indicator products developed through exploitation of Ocean Colour and Sea Surface Temperature data to derive correlations between the environmental situation and the biological status (maturation stage, recruitment and abundance rates) of the fish and shellfish studied. Developed in close collaboration with key stakeholders in the aquaculture and fishery sectors, the SAFI project proposes synthetic indicators for the species of critical importance to regional fisheries and aquaculture sectors.

  16. Coulomb energy difference as a probe of isospin-symmetry breaking in the upper fp-shell nuclei

    CERN Document Server

    Kaneko, K; Sun, Y; Tazaki, S; de Angelis, G

    2012-01-01

    The anomaly in Coulomb energy differences (CED) between the isospin T=1 states in the odd-odd N=Z nucleus 70Br and the analogue states in its even-even partner 70Se has remained a puzzle. This is a direct manifestation of isospin-symmetry breaking in effective nuclear interactions. Here, we perform large-scale shell-model calculations for nuclei with A=66-78 using the new filter diagonalization method based on the Sakurai-Sugiura algorithm. The calculations reproduce well the experimental CED. The observed negative CED for A=70 are accounted for by the cross-shell neutron excitations from the fp-shell to the g9/2 intruder orbit with the enhanced electromagnetic spin-orbit contribution at this special nucleon number.

  17. Siderophore production by Pseudomonas aeruginosa FP6, a biocontrol strain for Rhizoctonia solani and Colletotrichum gloeosporioides causing diseases in chilli

    Directory of Open Access Journals (Sweden)

    Bakthavatchalu Sasirekha

    2016-07-01

    Full Text Available Siderophores are compounds secreted under low iron stress, which act as specific ferric iron chelating agents. Owing to their potential in the biological control of fungal phytopathogens, they may be used as an alternative strategy to chemical control. Pseudomonas aeruginosa FP6, previously isolated from rhizospheric soil samples was screened for its siderophore production on a chrome-azurol S agar plate. Change in the colour of the chrome-azurol S agar from blue to orange red confirmed the siderophore producing ability of P. aeruginosa FP6. The effects of various physicochemical parameters on siderophore production were studied. The maximum siderophore production was obtained in succinate medium (125 μM followed by King's B medium (105 μM. The presence of sucrose and mannitol increased the siderophore production. Yeast extract proved to be the most suitable nitrogen source. Media supplemented with Pb2+, Mn2+ and Mg2+ showed appreciable siderophore production as well as growth of cultures. An increase in the iron concentration favoured growth but substantially reduced siderophore production. The strain when tested for its in-vitro antagonistic activity against Rhizoctonia solani and Colletotrichum gloeosporioides on King's B media, with and without FeCl3, showed a significant reduction in R. solani growth with FeCl3 supplementation compared to the control (without FeCl3, suggesting the role of siderophore mediated antagonism of R. solani. Antifungal activity was not influenced by FeCl3 in the case of C. gloeosporioides, suggesting the presence of other antagonistic mechanisms.

  18. New Improved Indirect Measurement of the 19F(p, α)16O Reaction at Energies of Astrophysical Relevance

    Science.gov (United States)

    Indelicato, I.; La Cognata, M.; Spitaleri, C.; Burjan, V.; Cherubini, S.; Gulino, M.; Hayakawa, S.; Hons, Z.; Kroha, V.; Lamia, L.; Mazzocco, M.; Mrazek, J.; Pizzone, R. G.; Romano, S.; Strano, E.; Torresi, D.; Tumino, A.

    2017-08-01

    Fluorine abundance determination is of great importance in stellar physics to understand s-elements production and mixing processes in asymptotic giant branch (AGB) stars. Up to now, theoretical models overproduce F abundances in AGB stars with respect to the observed values, thus calling for further investigation of the reactions involving fluorine. In particular, the 19F(p, α)16O reaction is the main destruction channel of fluorine at the bottom of the convective envelope in AGB stars, an H-rich environment where it can experience temperatures high enough to determine its destruction, owing to additional mixing processes. In this paper the Trojan horse method (THM) was used to extract the 19F(p, α 0)16O S-factor in the energy range of astrophysical interest (E cm ≈ 0-1 MeV). This is the most relevant channel at the low temperatures (few 107 K) characterizing the bottom of the convective envelope, according to current knowledge. A previous indirect experiment using the THM has observed three resonances in the energy regions below E cm ≈ 450 keV. These energies correspond to typical AGB temperatures, thus implying a significant increase in the reaction rate. Statistics are scarce for performing an accurate separation between resonances, preventing one from drawing a quantitative conclusion about their total widths and spin parities. Before THM measurement, only extrapolations were available below about 500 keV, showing a non-resonant behavior that sharply contradicts the trend of the astrophysical factor at higher energies. A new experiment has been performed to verify the measured TH astrophysical factor and to perform more accurate spectroscopy of the involved resonances.

  19. Evaluating item endorsement rates for the MMPI-2-RF F-r and Fp-r scales across ethnic, gender, and diagnostic groups with a forensic inpatient sample.

    Science.gov (United States)

    Glassmire, David M; Jhawar, Amandeep; Burchett, Danielle; Tarescavage, Anthony M

    2017-05-01

    The Minnesota Multiphasic Personality Inventory-2 (MMPI-2) F(p) (Infrequency-Psychopathology) scale was developed to measure overreporting in a manner that was minimally confounded by genuine psychopathology, which was a problem with using the MMPI-2 F (Infrequency) scale among patients with severe mental illness. Although revised versions of both of these scales are included on the MMPI-2-Restructured Form and used in a forensic context, no item-level research has been conducted on their sensitivity to genuine psychopathology among forensic psychiatric inpatients. Therefore, we examined the psychometric properties of the scales in a sample of 438 criminally committed forensic psychiatric inpatients who were adjudicated as not guilty by reason of insanity and had no known incentive to overreport. We found that 20 of the 21 Fp-r items (95.2%) demonstrated endorsement rates ≤ 20%, with 14 of the items (66.7%) endorsed by less than 10% of the sample. Similar findings were observed across genders and across patients with mood and psychotic disorders. The one item endorsed by more than 20% of the sample had a 23.7% overall endorsement rate and significantly different endorsement rates across ethnic groups, with the highest endorsements occurring among Hispanic/Latino (43.3% endorsement rate) patients. Endorsement rates of F-r items were generally higher than for Fp-r items. At the scale level, we also examined correlations with the Restructured Clinical Scales and found that Fp-r demonstrated lower correlations than F-r, indicating that Fp-r is less associated with a broad range of psychopathology. Finally, we found that Fp-r demonstrated slightly higher specificity values than F-r at all T score cutoffs. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  20. [{sup 123}]FP-CIT SPECT scans initially rated as normal became abnormal over time in patients with probable dementia with Lewy bodies

    Energy Technology Data Exchange (ETDEWEB)

    Zande, J.J. van der; Scheltens, P.; Lemstra, A.W. [VU Medical Center Alzheimer Center, Amsterdam (Netherlands); Booij, J. [Academic Medical Center, Department of Nuclear Medicine, Amsterdam (Netherlands); Raijmakers, P.G.H.M. [VU Medical Center, Department of Nuclear Medicine, Amsterdam (Netherlands)

    2016-06-15

    Decreased striatal dopamine transporter (DAT) binding on SPECT imaging is a strong biomarker for the diagnosis of dementia with Lewy bodies (DLB). There is still a lot of uncertainty about patients meeting the clinical criteria for probable DLB who have a normal DAT SPECT scan (DLB/S-). The aim of this study was to describe the clinical and imaging follow-up in these patients, and compare them to DLB patients with abnormal baseline scans (DLB/S+). DLB patients who underwent DAT imaging ([{sup 123}I]FP-CIT SPECT) were selected from the Amsterdam Dementia Cohort. All [{sup 123}I]FP-CIT SPECT scans were evaluated independently by two nuclear medicine physicians and in patients with normal scans follow-up imaging was obtained. We matched DLB/S- patients for age and disease duration to DLB/S+ patients and compared their clinical characteristics. Of 67 [{sup 123}I]FP-CIT SPECT scans, 7 (10.4 %) were rated as normal. In five DLB/S- patients, a second [{sup 123}I]FP-CIT SPECT was performed (after on average 1.5 years) and these scans were all abnormal. No significant differences in clinical characteristics were found at baseline. DLB/S- patients could be expected to have a better MMSE score after 1 year. This study was the first to investigate DLB patients with the initial [{sup 123}I]FP-CIT SPECT scan rated as normal and subsequent scans during disease progression rated as abnormal. We hypothesize that DLB/S- scans could represent a relatively rare DLB subtype with possibly a different severity or spread of alpha-synuclein pathology (''neocortical predominant subtype''). In clinical practice, if an alternative diagnosis is not imminent in a DLB/S- patient, repeating [{sup 123}I]FP-CIT SPECT should be considered. (orig.)

  1. Machine learning models for the differential diagnosis of vascular parkinsonism and Parkinson's disease using [{sup 123}I]FP-CIT SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Huertas-Fernandez, I.; Benitez-Rivero, S.; Jesus, S.; Caceres-Redondo, M.T.; Martin-Rodriguez, J.F.; Carrillo, F. [Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Unidad de Trastornos del Movimiento, Servicio de Neurologia y Neurofisiologia Clinica, Seville (Spain); Garcia-Gomez, F.J.; Marin-Oyaga, V.A.; Lojo, J.A. [Hospital Universitario Virgen del Rocio, Servicio de Medicina Nuclear, UDIM, Seville (Spain); Garcia-Solis, D. [Hospital Universitario Virgen del Rocio, Servicio de Medicina Nuclear, UDIM, Seville (Spain); Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Seville (Spain); Mir, P. [Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Unidad de Trastornos del Movimiento, Servicio de Neurologia y Neurofisiologia Clinica, Seville (Spain); Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Seville (Spain)

    2015-01-15

    The study's objective was to develop diagnostic predictive models using data from two commonly used [{sup 123}I]FP-CIT SPECT assessment methods: region-of-interest (ROI) analysis and whole-brain voxel-based analysis. We included retrospectively 80 patients with vascular parkinsonism (VP) and 164 patients with Parkinson's disease (PD) who underwent [{sup 123}I]FP-CIT SPECT. Nuclear-medicine specialists evaluated the scans and calculated bilateral caudate and putamen [{sup 123}I]FP-CIT uptake and asymmetry indices using BRASS software. Statistical parametric mapping (SPM) was used to compare the radioligand uptake between the two diseases at the voxel level. Quantitative data from these two methods, together with potential confounding factors for dopamine transporter availability (sex, age, disease duration and severity), were used to build predictive models following a tenfold cross-validation scheme. The performance of logistic regression (LR), linear discriminant analysis and support vector machine (SVM) algorithms for ROI data, and their penalized versions for SPM data (penalized LR, penalized discriminant analysis and SVM), were assessed. Significant differences were found in the ROI analysis after covariate correction between VP and PD patients in [{sup 123}I]FP-CIT uptake in the more affected side of the putamen and the ipsilateral caudate. Age, disease duration and severity were also found to be informative in feeding the statistical model. SPM localized significant reductions in [{sup 123}I]FP-CIT uptake in PD with respect to VP in two specular clusters comprising areas corresponding to the left and right striatum. The diagnostic predictive accuracy of the LR model using ROI data was 90.3 % and of the SVM model using SPM data was 90.4 %. The predictive models built with ROI data and SPM data from [{sup 123}I]FP-CIT SPECT provide great discrimination accuracy between VP and PD. External validation of these methods is necessary to confirm their

  2. Expression of eicosanoid receptors subtypes and eosinophilic inflammation: implication on chronic rhinosinusitis

    Directory of Open Access Journals (Sweden)

    Van Cauwenberge Paul

    2006-05-01

    Full Text Available Abstract Background Eicosanoid receptors are G-protein-coupled receptors playing an important immunomodulatory role in airway diseases. However, there is little information on the expression of these receptors and their link with eosinophilic inflammation in paranasal sinus diseases. We aimed with this study to investigate the tissue expression of leukotrienes and prostaglandin E2 receptors in chronic rhinosinusitis patients and the link of this regulation with eosinophilic inflammation. Methods Samples were prepared from nasal tissue of patients with chronic rhinosinusitis without nasal polyps (CRS, n = 11, with nasal polyps (CRS-NP, n = 13 and healthy subjects (Controls, n = 6. mRNA expression of CysLT1, CysLT2, BLT1, BLT2, E-prostanoid receptors (EP1, EP2, EP3, EP4 and sol-IL-5Rα was determined by real-time PCR. Concentrations of PGE2, LTC4/D4/E4, LTB4 and sol-IL-5Rα were determined by ELISA and of ECP by ImmunoCap. Protein expression and tissue localization of eicosanoid receptors and activated eosinophils were evaluated by immunohistochemistry. Results CysLT1 mRNA expression was significantly increased in CRS-NP compared to CRS and controls, and CRS compared to controls, whereas CysLT2 mRNA was enhanced in both CRS groups without differences between them. Levels of both receptors correlated to the number of activated eosinophils, sol-IL-5Rα, ECP and LTC4/D4/E4 concentrations in the disease groups. PGE2 protein concentrations and prostanoid receptors EP1 and EP3 were down-regulated in the CRS-NP tissue vs. CRS and controls, whereas EP2 and EP4 expression was enhanced in CRS and CRS-NP patients vs. controls. No differences in BLT receptors were observed between patients and controls. Conclusion CyLTs receptors are up-regulated in nasal polyp tissue and their expression correlate with eosinophilic inflammation supporting previous results. Eicosanoid receptors mRNA pattern observed suggests that down-regulation of EP1 and EP3 in CRS-NP and

  3. Development of methodology for alternative testing strategies for the assessment of the toxicological profile of nanoparticles used in medical diagnostics. NanoTEST - EC FP7 project

    Energy Technology Data Exchange (ETDEWEB)

    Dusinska, Maria; Fjellsbo, Lise Maria; Heimstad, Eldbjorg; Harju, Mikael; Bartonova, Alena [Norwegian Institute for Air Research (Norway)], E-mail: dusinska@szu.sk; Tran, Lang [Institute of Occupational Medicine (United Kingdom); Juillerat-Jeanneret, Lucienne; Halamoda, Blanka [Centre Hospitalier Universitaire Vaudois (Switzerland); Marano, Francelyne; Boland, Sonja [University Paris Diderot Paris7 (France); Saunders, Margaret; Cartwright, Laura; Carreira, Sara; Thawley, Susan [University Hospitals Bristol NHS Foundation Trust (United Kingdom); Whelan, Maurice; Klein, Christoph [EC - Directorate General Joint Research Centre (Italy); Housiadas, Christos [National Centre for Scientific Research Demokritos (Greece); Volkovova, Katarina; Tulinska, Jana; Beno, Milan [Slovak Medical University (Slovakia)] (and others)

    2009-05-01

    Nanoparticles (NPs) have unique, potentially beneficial properties, but their possible impact on human health is still not known. The area of nanomedicine brings humans into direct contact with NPs and it is essential for both public confidence and the nanotech companies that appropriate risk assessments are undertaken in relation to health and safety. There is a pressing need to understand how engineered NPs can interact with the human body following exposure. The FP7 project NanoTEST (www.nanotest-fp7.eu) addresses these requirements in relation to the toxicological profile of NPs used in medical diagnostics.

  4. TP receptor as a therapeutic target in atherosclerosis and related cardiovascular diseases.

    Science.gov (United States)

    Ishizuka, Toshiaki; Higashino, Hideaki

    2006-11-01

    It had already showed that several thromboxane A(2) receptor (TP receptor) antagonists might be utilized in the treatment of cardiovascular diseases. In addition, recent reports suggested that TP receptor antagonism may be able to restrict vascular inflammation in atherosclerotic vessels. In particular, S18886 has been developed as a non-prostanoid TP receptor antagonist derived from sulotroban that is characterized by a tetrahydronaphthalene ring as a spacer between the 4-cholophenylsulfonamide group and carboxylic acid. Several reports using experimental animal models of atherosclerosis indicated that S18886 caused a regression of advanced atherosclerosis. More recently, several studies and patents showed that new thromboxane modulators combined with another pharmacological activities have been developed. Ohtake et al. discovered TRA-418 (a benzene-condensed heterocyclic derivative) having a TP receptor antagonistic activity and a prostaglandin I(2) receptor agonistic activity. Cesagrande found that 4-methyl-N- (4-trans-nitrooxycyclohexyl)-N-(3-pyridinylmethyl)-1,3- benzenedicarboxamide is endowed with anti-thromboxane and NO-donor actions. Oketani et al. discovered that E3040, a novel benzothiazole derivative, inhibited TXA(2) synthase and 5-LO activities. EK112, a combined angiotensin II and TP receptor antagonist, was developed. These new compounds may be able to restrict further infiltration of inflammatory cells in atherosclerotic vessels, thus stabilizing vulnerable plaques in the related cardiovascular diseases.

  5. Exacerbation of Intracranial Aneurysm and Aortic Dissection in Hypertensive Rat Treated With the Prostaglandin F–Receptor Antagonist AS604872

    National Research Council Canada - National Science Library

    Fukuda, Miyuki; Aoki, Tomohiro; Manabe, Toshiaki; Maekawa, Akiko; Shirakawa, Takayuki; Kataoka, Hiroharu; Takagi, Yasushi; Miyamoto, Susumu; Narumiya, Shuh

    2014-01-01

    .... Given the involvement of prostaglandin F2α and its receptor, FP, in extracellular matrix remodeling in a mouse model of pulmonary fibrosis, here we induced hypertension and IA in rats by salt loading and hemi-lateral ligation of renal...

  6. Implementation of the European multicentre database of healthy controls for [(123)I]FP-CIT SPECT increases diagnostic accuracy in patients with clinically uncertain parkinsonian syndromes

    DEFF Research Database (Denmark)

    Albert, Nathalie L; Unterrainer, Marcus; Diemling, Markus

    2016-01-01

    PURPOSE: Even though [(123)I]FP-CIT SPECT provides high accuracy in detecting nigrostriatal cell loss in neurodegenerative parkinsonian syndromes (PS), some patients with an inconclusive diagnosis remain. We investigated whether the diagnostic accuracy in patients with clinically uncertain PS...

  7. Repeated administration of D-amphetamine induces loss of [{sup 123}I]FP-CIT binding to striatal dopamine transporters in rat brain: a validation study

    Energy Technology Data Exchange (ETDEWEB)

    Booij, Jan [Department of Nuclear Medicine, Academic Medical Center, 1105 AZ Amsterdam (Netherlands)]. E-mail: j.booij@amc.uva.nl; Bruin, Kora de [Department of Nuclear Medicine, Academic Medical Center, 1105 AZ Amsterdam (Netherlands); Gunning, W. Boudewijn [Department of Neurology, Epilepsy Centre Kempenhaeghe, 5590 AB Heeze (Netherlands)

    2006-04-15

    In recent years, several PET and SPECT studies have shown loss of striatal dopamine transporter (DAT) binding in amphetamine (AMPH) users. However, the use of DAT SPECT tracers to detect AMPH-induced changes in DAT binding has not been validated. We therefore examined if repeated administration of D-AMPH or methamphetamine (METH) may induce loss of binding to striatal DATs in rats by using an experimental biodistribution study design and a SPECT tracer for the DAT ([{sup 123}I]FP-CIT). Methods: Groups of male rats (n=10 per group) were treated with D-AMPH (10 mg/kg body weight), METH (10 mg/kg body weight), or saline, twice a day for 5 consecutive days. Five days later, [{sup 123}I]FP-CIT was injected intravenously, and 2 h later, the rats were sacrificed and radioactivity was assayed. Results: In D-AMPH but not METH-treated rats, striatal [{sup 123}I]FP-CIT uptake was significantly lower (approximately 17%) than in the control group. Conclusion: These data show that [{sup 123}I]FP-CIT can be used to detect AMPH-induced changes in DAT binding and may validate the use of DAT radiotracers to study AMPH-induced changes in striatal DAT binding in vivo.

  8. ENVIRONMENTAL TECHNOLOGY VERIFICATION, TEST REPORT OF CONTROL OF BIOAEROSOLS IN HVAC SYSTEMS, FILTRATION GROUP, AEROSTAR FP-98 MINIPLEAT V-BLANK FILTER

    Science.gov (United States)

    The Environmental Technology Verification report discusses the technology and performance of the AeroStar FP-98 Minipleat V-Bank Filter air filter for dust and bioaerosol filtration manufactured by Filtration Group. The pressure drop across the filter was 137 Pa clean and 348 Pa ...

  9. Fuzzy-PI-based centralised control of semi-isolated FP-SEPIC/ZETA BDC in a PV/battery hybrid system

    Science.gov (United States)

    Mahendran, Venmathi; Ramabadran, Ramaprabha

    2016-11-01

    Multiport converters with centralised controller have been most commonly used in stand-alone photovoltaic (PV)/battery hybrid system to supply the load smoothly without any disturbances. This study presents the performance analysis of four-port SEPIC/ZETA bidirectional converter (FP-SEPIC/ZETA BDC) using various types of centralised control schemes like Fuzzy tuned proportional integral controller (Fuzzy-PI), fuzzy logic controller (FLC) and conventional proportional integral (PI) controller. The proposed FP-SEPIC/ZETA BDC with various control strategy is derived for simultaneous power management of a PV source using distributed maximum power point tracking (DMPPT) algorithm, a rechargeable battery, and a load by means of centralised controller. The steady state and the dynamic response of the FP-SEPIC/ZETA BDC are analysed using three different types of controllers under line and load regulation. The Fuzzy-PI-based control scheme improves the dynamic response of the system when compared with the FLC and the conventional PI controller. The power balance between the ports is achieved by pseudorandom carrier modulation scheme. The response of the FP-SEPIC/ZETA BDC is also validated experimentally using hardware prototype model of 500 W system. The effectiveness of the control strategy is validated using simulation and experimental results.

  10. Clinical features and {sup 123}I-FP-CIT SPECT imaging in drug-induced parkinsonism and Parkinson's disease

    Energy Technology Data Exchange (ETDEWEB)

    Diaz-Corrales, Francisco J.; Escobar-Delgado, Teresa [Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Unidad de Trastornos del Movimiento, Servicio de Neurologia, Instituto de Biomedicina de Sevilla, Seville (Spain); Sanz-Viedma, Salome [Hospital Universitario Virgen del Rocio, Unidad Diagnostica de Medicina Nuclear, Seville (Spain); Garcia-Solis, David [Hospital Universitario Virgen del Rocio, Unidad Diagnostica de Medicina Nuclear, Seville (Spain); Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Seville (Spain); Mir, Pablo [Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Unidad de Trastornos del Movimiento, Servicio de Neurologia, Instituto de Biomedicina de Sevilla, Seville (Spain); Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Seville (Spain); Hospital Universitario Virgen del Rocio, Unidad de Trastornos del Movimiento. Servicio de Neurologia, Seville (Spain)

    2010-03-15

    To determine clinical predictors and accuracy of {sup 123}I-FP-CIT SPECT imaging in the differentiation of drug-induced parkinsonism (DIP) and Parkinson's disease (PD). Several clinical features and {sup 123}I-FP-CIT SPECT images in 32 patients with DIP, 25 patients with PD unmasked by antidopaminergic drugs (PDu) and 22 patients with PD without a previous history of antidopaminergic treatment (PDc) were retrospectively evaluated. DIP and PD shared all clinical features except symmetry of parkinsonian signs which was more frequently observed in patients with DIP (46.9%) than in patients with PDu (16.0%, p<0.05) or PDc (4.5%, p<0.01). Qualitatively {sup 123}I-FP-CIT SPECT images were normal in 29 patients with DIP (90.6%) and abnormal in all patients with PD, and this imaging technique showed high levels of accuracy. DIP and PD are difficult to differentiate based on clinical signs. The precision of clinical diagnosis could be reliably enhanced by {sup 123}I-FP-CIT SPECT imaging. (orig.)

  11. No difference in striatal dopamine transporter availability between active smokers, ex-smokers and non-smokers using (123I)FP-CIT (DaTSCAN) and SPECT

    DEFF Research Database (Denmark)

    Thomsen, G; Knudsen, Gitte Moos; Jensen, PS;

    2013-01-01

    tobacco smoking: (1) non-smokers (n = 64), (2) ex-smokers (n = 39) and (3) active smokers (n = 26). For imaging of the DAT availability, we used [123I]FP-CIT (DaTSCAN) and single photon emission computed tomography (SPECT). Data were collected in collaboration between 13 SPECT centres located in 10...

  12. Potential environmental benefits of improving recycling of polyolefines – LCA of Magnetic density separation (MDS) developed in the EU FP7 funded project W2Plastic

    DEFF Research Database (Denmark)

    Olsen, Stig Irving; Bonou, Alexandra

    2012-01-01

    The core of the EU FP7 funded project W2Plastic is development of a magnetic density separation (MDS) of polyolefines in order to improve the sorting efficiency of these polymer types in different waste fractions. As part of the project a life cycle assessment is performed in order to firstly...

  13. Comparison of FP-7 and S-2 Ahmed glaucoma valve implantation in refractory glaucoma patients for short-term follow-up

    Institute of Scientific and Technical Information of China (English)

    BAI Yu-jing; LI Yi-qing; CHAI Fang; YANG Xue-jiao; ZHANG Yi-chong; WEI Yan-tao; HUANG Jing-jing; GE Jian; ZHUO Ye-hong

    2011-01-01

    Background Ahmed glaucoma valves (AGV) has been used for decades, but there is no detailed report about the efficacy of AGV in Chinese glaucoma patients. This study aimed to compare the intraocular pressure (IOP) lowering efficacy and side effects of S-2 polypropylene and PF-7 silicone AGV implantation in Chinese refractory glaucoma patients.Methods Patients were divided into S-2 model AGV group and FP-7 model AGV group. The complete and qualified surgical success rate, change of IOP, number of anti-glaucoma medications used and postoperative complications were recorded and analyzed.Results Average follow-up time was comparable between two groups. IOP was reduced from (37.9±12.7) mmHg preoperatively to (17.3±5.3) mmHg at the last follow-up in S-2 group and reduced from (39.9±14.4) mmHg to (17.7±4.9)mmHg in FP-7 group. Anti-glaucoma medications were reduced from 3.8±0.2 to 1.5±0.2 in S-2 group, and 3.5±0.2 to 0.7±0.2 in FP-7 groups. The cumulative success rates were comparable in two groups, which were 61.2% and 72.1% in S-2 group and FP-7 group respectively. When IOP reduction criteria was used, complete success rates were 30.6% and 51.2% for S-2 and FP-7 groups, and qualified success rates were 86.1% and 92.7% separately. In both groups, the major complication was hypotony, and the previous trabeculectomy of patients was the major risk factor for surgery failure.Conclusions In this short-term retrospective study, S-2 AGV is showed at least as effective as FP-7 AGV in IOP reduction, but associated with higher rate of complications. Previous trabeculectomy is a principle risk factor for AGV implantation failure. These clinical outcomes are important for converting use of the FP-7 silicon AGV in Chinese refractory glaucoma patients.

  14. Applications and Compatibility Laws of Associated Prescriptions of Siwu Tang Based on FP-Growth Algorithm%基于FP-Growth算法的四物汤类方配伍规律及应用研究

    Institute of Scientific and Technical Information of China (English)

    陶静; 范欣生; 张欢; 段金廒; 王崇峻; 刘正

    2010-01-01

    目的:运用数据挖掘方法,挖掘单味药、药对之间的关联关系,分析类方和药对内部的组成关系,探讨四物汤的配伍规律.方法:收集四物汤类方3487首,针对四物汤药物配伍和药对特征,对单味药、药对之间的关联关系,分别采用频繁模式、FP-Growth算法.结果:获得置信度>0.15的四物汤配伍常用药有甘草、人参、肉桂、茯苓,常用药对有当归-甘草、川芎-甘草、地黄-甘草、芍药-甘草、人参-甘草、茯苓-甘草.结论:四物汤常用配伍主要有补益药、行气药、温里药、清热药、活血化瘀药,并由此形成常用药对,在妇科疾病的治疗中得到了广泛的应用.

  15. Combined visual and semi-quantitative assessment of (123)I-FP-CIT SPECT for the diagnosis of dopaminergic neurodegenerative diseases.

    Science.gov (United States)

    Ueda, Jun; Yoshimura, Hajime; Shimizu, Keiji; Hino, Megumu; Kohara, Nobuo

    2017-07-01

    Visual and semi-quantitative assessments of (123)I-FP-CIT single-photon emission computed tomography (SPECT) are useful for the diagnosis of dopaminergic neurodegenerative diseases (dNDD), including Parkinson's disease, dementia with Lewy bodies, progressive supranuclear palsy, multiple system atrophy, and corticobasal degeneration. However, the diagnostic value of combined visual and semi-quantitative assessment in dNDD remains unclear. Among 239 consecutive patients with a newly diagnosed possible parkinsonian syndrome who underwent (123)I-FP-CIT SPECT in our medical center, 114 patients with a disease duration less than 7 years were diagnosed as dNDD with the established criteria or as non-dNDD according to clinical judgment. We retrospectively examined their clinical characteristics and visual and semi-quantitative assessments of (123)I-FP-CIT SPECT. The striatal binding ratio (SBR) was used as a semi-quantitative measure of (123)I-FP-CIT SPECT. We calculated the sensitivity and specificity of visual assessment alone, semi-quantitative assessment alone, and combined visual and semi-quantitative assessment for the diagnosis of dNDD. SBR was correlated with visual assessment. Some dNDD patients with a normal visual assessment had an abnormal SBR, and vice versa. There was no statistically significant difference between sensitivity of the diagnosis with visual assessment alone and semi-quantitative assessment alone (91.2 vs. 86.8%, respectively, p = 0.29). Combined visual and semi-quantitative assessment demonstrated superior sensitivity (96.7%) to visual assessment (p = 0.03) or semi-quantitative assessment (p = 0.003) alone with equal specificity. Visual and semi-quantitative assessments of (123)I-FP-CIT SPECT are helpful for the diagnosis of dNDD, and combined visual and semi-quantitative assessment shows superior sensitivity with equal specificity.

  16. Evaluation of WO 2012/177618 A1 and US-2014/0179750 A1: Novel small molecule antagonists of PGE2 receptor EP2

    Science.gov (United States)

    Ganesh, Thota

    2016-01-01

    Recent studies underscore that prostaglandin-E2 (PGE2) exerts mostly proinflammatory effects in chronic CNS and peripheral disease models, mainly through a specific prostanoid receptor EP2. However, very few highly characterized EP2 receptor antagonists have been reported until recently, when Pfizer and Emory University published two distinct classes of EP2 antagonists with good potency, selectivity and pharmacokinetics. The purpose of this article is to evaluate recently published patents WO 2012177618 A1 and US-2014/0179750 A1 from Emory, which describe a number of cinnamic amide- and amide-derivatives as a potent antagonists of EP2 receptor, and their neuroprotective effects in in vitro and in an in vivo model. A selected compound from this patent(s) also attenuates prostate cancer cell growth and invasion in vitro, suggesting these compounds should be developed for therapeutic use. PMID:25772215

  17. Evaluation of WO 2012/177618 A1 and US-2014/0179750 A1: novel small molecule antagonists of prostaglandin-E2 receptor EP2.

    Science.gov (United States)

    Ganesh, Thota

    2015-07-01

    Recent studies underscore that prostaglandin-E2 exerts mostly proinflammatory effects in chronic CNS and peripheral disease models, mainly through a specific prostanoid receptor EP2. However, very few highly characterized EP2 receptor antagonists have been reported until recently, when Pfizer and Emory University published two distinct classes of EP2 antagonists with good potency, selectivity and pharmacokinetics. The purpose of this article is to evaluate recently published patents WO 2012/177618 A1 and US-2014/0179750 A1 from Emory, which describe a number of cinnamic amide- and amide-derivatives as a potent antagonists of EP2 receptor, and their neuroprotective effects in in vitro and in an in vivo model. A selected compound from this patent(s) also attenuates prostate cancer cell growth and invasion in vitro, suggesting these compounds should be developed for therapeutic use.

  18. The implementation of the Open Access paradigm to the EC-FP7 MED-SUV (Mediterranean Supersite Volcanoes) project

    Science.gov (United States)

    Puglisi, Giuseppe; Brito, Fabrice; Caumont, Hervé; D'Auria, Luca; Fernandez, José; Mazzetti, Paolo; Mathieu, Pierre Philippe; Nativi, Stefano; Papeschi, Fabrizio; Pepe, Antonio; Reitano, Danilo; Sangianantoni, Agata; Scarpato, Giovanni; Spampinato, Letizia

    2016-04-01

    The overall goal of the EC-FP7 Mediterranean Supersite Volcanoes (MED-SUV) project is to apply the rationale of the Supersites GEO initiative to Campi Flegrei/Vesuvius and Mt. Etna to reduce the volcanic risk, by improving the understanding of the underlying geophysical processes, through the integration and sharing of the in-situ and Earth Observation (EO) data sets and the implementation of new instruments and monitoring systems. The project involves 24 EU and no-EU partners, including research and academic institutions, space agencies and SMEs. In this framework, the application of the Open Access paradigm has offered the opportunity to study and apply practical solutions concerning the data management (i.e. data polices, foreground exploitation and sustainability), intellectual property rights (i.e., ownership, licences, agreements) and technical issues (i.e., design and implementation of an interoperability e-infrastructure, access systems, etc.). This contribution presents pro and cons encountered in the project, as well as the main outcomes of the implementation of the Open Access to the Italian Supersites. This experience will be exploited in the building of international research infrastructures, such as EPOS, and the outcomes of the project will contribute to foster the Open Access to the research data in a wide context, as the GEO-GEOSS framework.

  19. Study of proton resonances in 18Ne via resonant elastic scattering of 17F+p and its astrophysical implication

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    The proton resonant properties in 18Ne, which determine the reaction rate of the key stellar 14O(α,p)17F reaction, have been studied by using a technique of proton resonant elastic scattering of 17F+p. A 4.22 MeV/nucleon 17F radioactive ion (RI) beam was produced via a projectile-fragmentation reaction, and separated by a Radioactive Ion Beam Line in Lanzhou (RIBLL). By bombarding a thick (CH2)n target, the energy spectra of the recoiled protons were measured by two ΔE-E silicon telescopes at the center-of-mass scattering angles of θc.m.≈175°±5°, θc.m.≈152°±8°, respectively. Several proton resonances in 18Ne were ob served clearly. A further R-matrix analysis of the experimental data is under way to determine the resonant parameters. The present work reports the preliminary results briefly.

  20. The FP420 R&D Project: Higgs and New Physics with forward protons at the LHC

    CERN Document Server

    Albrow, M.G.; Arneodo, Michele; Atoian, G.; Barlow, R.; Beaumont, W.; Bonnet, L.; Brandt, A.; Bussey, P.; Buttar, C.; Butterworth, J.M.; Carter, M.; Cox, B.E.; Dattola, D.; Da Via, C.; de Favereau, J.; D'Enterria, David; De Remigis, P.; De Roeck, Albert; De Wolf, Eddi A.; Duarte, P.; Ellis, John R.; Florins, B.; Forshaw, J.R.; Freestone, J.; Goulianos, Konstantin A.; Gronberg, J.; Grothe, M.; Gunion, J.F.; Hasi, J.; Heinemeyer, S.; Hollar, Jonathan J.; Houston, S.; Issakov, V.; Jones, Roger M.; Kelly, M.; Kenney, C.; Khoze, V.A.; Kolya, S.; Konstantinidis, N.; Kowalski, H.; Lanni, F.; Larsen, H.E.; Liu, S.L.; Lyapine, A.; Loebinger, Frederick K.; Marshall, R.; Martin, A.D.; Monk, James William; Nasteva, Irina; Nemegeer, P.; Obertino, M.M.; Orava, R.; O'Shea, V.; Pal, A.; Parker, S.; Pater, J.; Perrot, A.L.; Pierzchala, T.; Pilkington, A.D.; Pinfold, James L.; Piotrzkowski, Krzysztof; Plano, W.; Poblaguev, A.; Popov, V.; Potter, K.M.; Radeka, V.; Rescia, S.; Roncarolo, F.; Rostovtsev, A.; Rouby, X.; Ruspa, M.; Ryskin, M.G.; Santoro, A.; Schul, N.; Sellers, G.; Solano, A.; Spivey, S.; Stirling, W.J.; Swoboda, D.; Tasevsky, M.; Thompson, R.; Tsang, T.; Van Mechelen, P.; Vilela Pereira, A.; Watts, S.J.; Warren, M.R.M.; Weiglein, G.; Wengler, T.; White, Sebastian N.; Winter, B.; Yao, Y.; Zaborov, D.; Zampieri, A.; Zeller, M.; Zhokin, A.

    2009-01-01

    We present the FP420 R&D project, which has been studying the key aspects of the development and installation of a silicon tracker and fast-timing detectors in the LHC tunnel at 420 m from the interaction points of the ATLAS and CMS experiments. These detectors would measure precisely very forward protons in conjunction with the corresponding central detectors as a means to study Standard Model (SM) physics, and to search for and characterise New Physics signals. This report includes a detailed description of the physics case for the detector and, in particular, for the measurement of Central Exclusive Production, pp --> p + phi + p, in which the outgoing protons remain intact and the central system phi may be a single particle such as a SM or MSSM Higgs boson. Other physics topics discussed are gamma-gamma and gamma-p interactions, and diffractive processes. The report includes a detailed study of the trigger strategy, acceptance, reconstruction efficiencies, and expected yields for a particular p p --> ...

  1. Correction of PF in systems with presence of harmonics; Correccion de FP en sistemas con presencia de armonicos

    Energy Technology Data Exchange (ETDEWEB)

    IMELHIA

    2005-07-01

    This document sets an example of a typical industrial plant and everything that this implies such as: an equivalent circuit and the form in which it acts as a source of harmonic currents, the initial problem: correction of the PF, the line current of this device, the current waveform (fundamental, fundamental plus fifth harmonica, h1 + h5 + h7, h1 {yields} h13 or h1 {yields} h25), the representation of harmonics, the Fourier series, the total distortion of the harmonics (THD), the classification of the harmonics, the capacitors, the reactance, the tuned filters h5 and h7, the high tension contaminated network, the extension of the network in LT, the intensities and the reactors banks. [Spanish] Este documento nos pone un ejemplo de una planta industrial tipica y todo lo que esta implica como: un circuito equivalente y la forma en que actua como una fuente de corrientes armonicas, el problema inicial: correccion FP, la corriente de linea de este dispositivo, la forma de onda en corriente (fundamental, fundamental mas quinta armonica, h1 + h5 + h7, h1 ? h13 o h1 ? h25), la representacion de armonicas, las series de Fourier, la distorsion total de las armonicas (THD), la clasificacion de las armonicas, los capacitores, la reactancia, los filtros sintonizados h5 y h7, la red de alta tension contaminada, la extension de red en BT, las intensidades y los bancos reactores.

  2. EUTEMPE-RX, an EC supported FP7 project for the training and education of medical physics experts in radiology.

    Science.gov (United States)

    Bosmans, H; Bliznakova, K; Padovani, R; Christofides, S; Van Peteghem, N; Tsapaki, V; Caruana, C J; Vassileva, J

    2015-07-01

    The core activity of the medical physics expert (MPE) is to ensure optimal use of ionising radiation in healthcare. It is essential that these healthcare professionals are trained to the highest level, defined as European Qualifications Framework for Lifelong Learning (EQF) level 8 by the European Commission's Radiation Protection Report 174 'Guidelines on the MPE'. The main objective of the EUTEMPE-RX project is to provide a model training scheme that allows the medical physicist in diagnostic and interventional radiology (D&IR) to reach this high level. A European network of partners was brought together in this FP7 EC project to ensure sufficient expertise in all aspects of the subject and to create a harmonised course programme. Targeted participants are medical physicists in D&IR in hospitals, engineers and scientists in medical device industries and officers working in regulatory authorities. Twelve course modules will be developed at EQF level 8, with radiation safety and diagnostic effectiveness being prevalent subjects. The modules will combine online with face-to-face teaching using a blended learning approach.

  3. Summary of important results and SCDAP/RELAP5 analysis for OECD LOFT experiment LP-FP-2

    Energy Technology Data Exchange (ETDEWEB)

    Coryell, E.W. [EG and G Idaho, Inc., Idaho Falls, ID (United States)

    1994-04-01

    This report summarizes significant technical findings from the LP-FP-2 Experiment sponsored by the Organization of Economic Cooperation and Development (OECD). It was the second, and final, fission product experiment conducted in the Loss-of-Fluid Test (LOFT) facility at the Idaho National Engineering Laboratory. The overall technical objective of the test was to contribute to the understanding of fuel rod behavior, hydrogen generation, and fission product release, transport, and deposition during a V-sequence accident scenario that resulted in severe core damage. An 11 by 11 test bundle, comprised of 100 prepressurized fuel rods, 11 control rods, and 10 instrumented guide tubes, was surrounded by an insulating shroud and contained in a specially designed central fuel module, that was inserted into the LOFT reactor. The simulated transient was a V-sequence loss-of-coolant accident scenario featuring a pipe break in the low pressure injection system line attached to the hot leg of the LOFT broken loop piping. The transient was terminated by reflood of the reactor vessel when the outer wall shroud temperature reached 1517 K. With sustained fission power and heat from oxidation and metal-water reactions, elevated temperatures resulted in zircaloy melting, fuel liquefaction, material relocation, and the release of hydrogen, aerosols, and fission products. A description and evaluation of the major phenomena, based upon the response of on line instrumentation, analysis of fission product data, postirradiation examination of the fuel bundle, and calculations using the SCDAP/RELAP5 computer code, are presented.

  4. Sustainable introduction of GM crops into european agriculture: a summary report of the FP6 SIGMEA research project*

    Directory of Open Access Journals (Sweden)

    Messéan Antoine

    2009-01-01

    Full Text Available In 2003, the European Commission established the principle of coexistence which refers to “the ability of farmers to make a practical choice between conventional, organic and GM-crop production, in compliance with the legal obligations for labelling and/or purity standards” and laid down guidelines defining the context of this coexistence1. In order to determine what is needed for the sustainable introduction of GM crops in Europe, the cross-disciplinary SIGMEA Research Project was set up to create a science-based framework to inform decision-makers. SIGMEA has (i collated and analysed European data on gene flow and the environmental impacts of the major crop species which are likely to be transgenic in the future (maize, rapeseed, sugar beet, rice, and wheat, (ii designed predictive models of gene flow at the landscape level, (iii analysed the technical feasibility and economic impacts of coexistence in the principal farming regions of Europe, (iv developed novel GMO detection methods, (v addressed legal issues related to coexistence, and (vi proposed public and farm scale decisionmaking tools, as well as guidelines regarding management and governance. This publishable version of the final activity report of the FP6 SIGMEA research project, covers the fourteen major issues under investigation.

  5. Spectral properties of actinide materials: Charge density self-consistent LDA+Hubbard I method in FP-LAPW basis

    Energy Technology Data Exchange (ETDEWEB)

    Kolorenc, Jindrich [Institute of Physics ASCR, Prague (Czech Republic); University of Hamburg, Hamburg (Germany); Shick, Alexander B. [Institute of Physics ASCR, Prague (Czech Republic); Havela, Ladislav [Charles University, Prague (Czech Republic); Lichtenstein, Alexander I. [University of Hamburg, Hamburg (Germany)

    2010-07-01

    We provide a numerically efficient procedure to perform LDA+Hubbard I calculations including self-consistency over the charge density in the FP-LAPW basis. The method is applied to Pu, Am, and PuAm and PuCe alloys. Our results for valence photoemission spectra (PES) agree with experimental data and with previous LDA+DMFT calculations. Analysis of the J=5/2 and J=7/2 contributions to the f-occupation supports the intermediate-coupling picture of f-states in heavy actinides. The electronic specific heat coefficient is calculated for PuAm and PuCe alloys in reasonable agreement with recent experiments. We show that Pu atoms keep their mixed-valence character in these alloys. Next, we study electronic and spectral properties of Pu-based superconductor PuCoGa{sub 5} and obtain good agreement with experimental PES. Finally, we analyze surface effects. In Pu monolayer, we find substantial modification of PES due to 5f-electron localization consistent with experimental observations.

  6. The FP420 R&D Project: Higgs and New Physics with forward protons at the LHC

    CERN Document Server

    Albrow, M G; Arneodo, Michele; Atoian, G; Barlow, R; Beaumont, W; Bonnet, L; Brandt, A; Bussey, P; Buttar, C; Butterworth, J M; Carter, M; Cox, B E; Dattola, D; Da Via, C; de Favereau, J; D'Enterria, David; De Remigis, P; De Roeck, Albert; De Wolf, Eddi A; Duarte, P; Ellis, John R.; Florins, B; Forshaw, J R; Freestone, J; Goulianos, Konstantin A; Gronberg, J; Grothe, M; Gunion, J F; Hasi, J; Heinemeyer, S; Hollar, Jonathan J; Houston, S; Issakov, V; Jones, Roger M; Kelly, M; Kenney, C; Khoze, V A; Kolya, S; Konstantinidis, N; Kowalski, H; Lanni, F; Larsen, H E; Liu, S L; Lyapine, A; Loebinger, Frederick K; Marshall, R; Martin, A D; Monk, James William; Nasteva, Irina; Nemegeer, P; Obertino, M M; Orava, R; O'Shea, V; Pal, A; Parker, S; Pater, J; Perrot, A L; Pierzchala, T; Pilkington, A D; Pinfold, James L; Piotrzkowski, Krzysztof; Plano, W; Poblaguev, A; Popov, V; Potter, K M; Radeka, V; Rescia, S; Roncarolo, F; Rostovtsev, A; Rouby, X; Ruspa, M; Ryskin, M G; Santoro, A; Schul, N; Sellers, G; Solano, A; Spivey, S; Stirling, W J; Swoboda, D; Tasevsky, M; Thompson, R; Tsang, T; Van Mechelen, P; Vilela Pereira, A; Watts, S J; Warren, M R M; Weiglein, G; Wengler, T; White, Sebastian N; Winter, B; Yao, Y; Zaborov, D; Zampieri, A; Zeller, M; Zhokin, A

    2009-01-01

    We present the FP420 R&D project, which has been studying the key aspects of the development and installation of a silicon tracker and fast-timing detectors in the LHC tunnel at 420 m from the interaction points of the ATLAS and CMS experiments. These detectors would measure precisely very forward protons in conjunction with the corresponding central detectors as a means to study Standard Model (SM) physics, and to search for and characterise New Physics signals. This report includes a detailed description of the physics case for the detector and, in particular, for the measurement of Central Exclusive Production, pp --> p + phi + p, in which the outgoing protons remain intact and the central system phi may be a single particle such as a SM or MSSM Higgs boson. Other physics topics discussed are gamma-gamma and gamma-p interactions, and diffractive processes. The report includes a detailed study of the trigger strategy, acceptance, reconstruction efficiencies, and expected yields for a particular p p --> ...

  7. PGE2 maintains the tone of the guinea pig trachea through a balance between activation of contractile EP1 receptors and relaxant EP2 receptors.

    Science.gov (United States)

    Säfholm, J; Dahlén, S-E; Delin, I; Maxey, K; Stark, K; Cardell, L-O; Adner, M

    2013-02-01

    The guinea pig trachea (GPT) is commonly used in airway pharmacology. The aim of this study was to define the expression and function of EP receptors for PGE(2) in GPT as there has been ambiguity concerning their role. Expression of mRNA for EP receptors and key enzymes in the PGE(2) pathway were assessed by real-time PCR using species-specific primers. Functional studies of GPT were performed in tissue organ baths. Expression of mRNA for the four EP receptors was found in airway smooth muscle. PGE(2) displayed a bell-shaped concentration-response curve, where the initial contraction was inhibited by the EP(1) receptor antagonist ONO-8130 and the subsequent relaxation by the EP(2) receptor antagonist PF-04418948. Neither EP(3) (ONO-AE5-599) nor EP(4) (ONO-AE3-208) selective receptor antagonists affected the response to PGE(2). Expression of COX-2 was greater than COX-1 in GPT, and the spontaneous tone was most effectively abolished by selective COX-2 inhibitors. Furthermore, ONO-8130 and a specific PGE(2) antibody eliminated the spontaneous tone, whereas the EP(2) antagonist PF-04418948 increased it. Antagonists of other prostanoid receptors had no effect on basal tension. The relaxant EP(2) response to PGE(2) was maintained after long-term culture, whereas the contractile EP(1) response showed homologous desensitization to PGE(2), which was prevented by COX-inhibitors. Endogenous PGE(2), synthesized predominantly by COX-2, maintains the spontaneous tone of GPT by a balance between contractile EP(1) receptors and relaxant EP(2) receptors. The model may be used to study interactions between EP receptors. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  8. Biotechnological Fluorescent Ligands of the Bradykinin B1 Receptor: Protein Ligands for a Peptide Receptor.

    Directory of Open Access Journals (Sweden)

    Xavier Charest-Morin

    Full Text Available The bradykinin (BK B1 receptor (B1R is a peculiar G protein coupled receptor that is strongly regulated to the point of being inducible in immunopathology. Limited clinical evidence suggests that its expression in peripheral blood mononuclear cells is a biomarker of active inflammatory states. In an effort to develop a novel imaging/diagnostic tool, we report the rational design and testing of a fusion protein that is a ligand of the human B1R but not likely to label peptidases. This ligand is composed of a fluorescent protein (FP (enhanced green FP [EGFP] or mCherry prolonged at its N-terminus by a spacer peptide and a classical peptide agonist or antagonist (des-Arg9-BK, [Leu8]des-Arg9-BK, respectively. The design of the spacer-ligand joint peptide was validated by a competition assay for [3H]Lys-des-Arg9-BK binding to the human B1R applied to 4 synthetic peptides of 18 or 19 residues. The labeling of B1R-expressing cells with EGFP or mCherry fused with 7 of such peptides was performed in parallel (microscopy. Both assays indicated that the best design was FP-(Asn-Glyn-Lys-des-Arg9-BK; n = 15 was superior to n = 5, suggesting benefits from minimizing steric hindrance between the FP and the receptor. Cell labeling concerned mostly plasma membranes and was inhibited by a B1R antagonist. EGFP-(Asn-Gly15-Lys-des-Arg9-BK competed for the binding of [3H]Lys-des-Arg9-BK to human recombinant B1R, being only 10-fold less potent than the unlabeled form of Lys-des-Arg9-BK to do so. The fusion protein did not label HEK 293a cells expressing recombinant human BK B2 receptors or angiotensin converting enzyme. This study identifies a modular C-terminal sequence that can be adapted to protein cargoes, conferring high affinity for the BK B1R, with possible applications in diagnostic cytofluorometry, histology and drug delivery (e.g., in oncology.

  9. Reduction of polyhedrin mRNA and protein expression levels in Sf9 and Hi5 cell lines, but not in Sf21 cells, infected with Autographa californica multiple nucleopolyhedrovirus fp25k mutants.

    Science.gov (United States)

    Cheng, Xin-Hua; Hillman, Christopher C; Zhang, Chuan-Xi; Cheng, Xiao-Wen

    2013-01-01

    During cell infection, the fp25k gene of baculoviruses frequently mutates, producing the few polyhedra (FP) per cell phenotype with reduced polyhedrin (polh) expression levels compared with wild-type baculoviruses. Here we report that the fp25k gene of the model baculovirus, Autographa californica multiple nucleopolyhedrovirus (AcMNPV), contains two hypermutable seven-adenine (A7) mononucleotide repeats (MNRs) that were mutated to A8 MNRs and a TTAA site that had host DNA insertions, producing fp25k mutants during Sf21 cell infection. The FP phenotype in Sf9 and Hi5 cells was more pronounced than in Sf21 cells. AcMNPV fp25k mutants produced similar levels of polyhedra or enhanced GFP, which were both under the control of the AcMNPV polh promoter for expression, in Sf21 cells but lower levels in Sf9 and Hi5 cells compared with AcMNPV with an intact fp25k gene. This correlated with the polh mRNA levels detected in each cell line. The majority of Sf21 cells infected with fp25 mutants showed high polh promoter-mediated GFP expression levels. Two cell lines subcloned from Sf21 cells that were infected with fp25k mutants showed different GFP expression levels. Furthermore, a small proportion of Hi5 cells infected with fp25k mutants showed higher production of polyhedra and GFP expression than the rest, and the latter was not correlated with increased m.o.i. Therefore, these data suggest that AcMNPV polh promoter-mediated gene expression activities differ in the three cell lines and are influenced by different cells within the cell line.

  10. Quantitation of dopamine transporter blockade by methylphenidate: first in vivo investigation using [{sup 123}I]FP-CIT and a dedicated small animal SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Nikolaus, Susanne; Wirrwar, Andreas; Antke, Christina; Arkian, Shahram; Mueller, Hans-Wilhelm; Larisch, Rolf [Heinrich-Heine University, Clinic of Nuclear Medicine, Duesseldorf (Germany); Schramm, Nils [Research Center Juelich, Central Laboratory for Electronics, Juelich (Germany)

    2005-03-01

    The aim of this study was to investigate the feasibility of assessing dopamine transporter binding after treatment with methylphenidate in the rat using a recently developed high-resolution small animal single-photon emission computed tomograph (TierSPECT) and [{sup 123}I]FP-CIT. [{sup 123}I]FP-CIT was administered intravenously 1 h after intraperitoneal injection of methylphenidate (10 mg/kg) or vehicle. Animals underwent scanning 2 h after radioligand administration. The striatum was identified by superimposition of [{sup 123}I]FP-CIT scans with bone metabolism and perfusion scans obtained with {sup 99m}Tc-DPD and {sup 99m}Tc-tetrofosmin, respectively. As these tracers do not pass the blood-brain barrier, their distribution permits the identification of extracerebral anatomical landmarks such as the orbitae and the harderian glands. The cerebellum was identified by superimposing [{sup 123}I]FP-CIT scans with images of brain perfusion obtained with {sup 99m}Tc-HMPAO. Methylphenidate-treated animals and vehicle-treated animals yielded striatal equilibrium ratios (V''{sub 3}) of 0.24{+-}0.26 (mean {+-} SD) and 1.09{+-}0.42, respectively (ttest, two-tailed, p<0.0001). Cortical V''{sub 3} values amounted to 0.05{+-}0.28 (methylphenidate) and 0.3{+-}0.39 (saline, p=0.176). This first in vivo study of rat dopamine transporter binding after pre-treatment with methylphenidate showed a mean reduction of 78% in striatal [{sup 123}I]FP-CIT accumulation. The results can be interpreted in terms of a pharmacological blockade in the rat striatum and show that in vivo quantitation of dopamine transporter binding is feasible with [{sup 123}I]FP-CIT and the TierSPECT. This may be of future relevance for in vivo investigations on rat models of attention deficit/hyperactivity disorder. Furthermore, our findings suggest that investigations in other animal models, e.g. of Parkinson's and Huntington's disease, may be feasible using SPECT radioligands and

  11. Improved visual [(123)I]FP-CIT SPECT interpretation for evaluation of parkinsonism by visual rating of parametric distribution volume ratio images.

    Science.gov (United States)

    Meyer, P T; Winz, O H; Dafotakis, M; Werner, C J; Krohn, T; Schäfer, W M

    2011-06-01

    Imaging of presynaptic dopamine transporters (DAT) by single-photon emission computed tomography (SPECT) and [(123)I]FP-CIT is an established method for differentiating between neurodegenerative and non-neurodegenerative parkinsonism. Whereas a region-of-interest (ROI) analysis is the method of choice for analyzing [(123)I]FP-CIT SPECT studies, visual image interpretations can also provide highly accurate results. The present study was undertaken to validate a visual reading system for parametric volume of distribution (DVR) [(123)I]FP-CIT SPECT images that combines the quantitative nature of ROI analyses and the simplicity of visual readings. A 9-step linear visual rating template for semi-quantitative DVR ratings of caudate nucleus and putamen was developed (VRDVR). The conventional 4-step visual reading system that is mainly based on the [(123)I]FP-CIT uptake pattern was used for comparison (VRP method). Six independent observers retrospectively rated the [(123)I]FP-CIT scans of 30 consecutive parkinsonism and tremor patients (N.=16 neurodegenerative, N.=14 non-neurodegenerative) using VRDVR and VRP. In addition, a highly trained investigator performed manual ROI analyses. The ROI analysis provided complete separation of both patient groups by comparing the lower DAT binding of both putamina (i.e., putamen contralateral to clinically most affected side in neurodegenerative parkinsonism). Using VRP, the two most experienced observers correctly classified all patients while 20 false-positive ratings occurred in the less experienced observers (mean area under the receiver operating characteristic curve [AUCROC] of all observers 0.93±0.07). The VRDVR ratings of the two most experienced observers did not overlap between patient groups, although at different VRDVR score cut-offs. Using the same VRDVR score cut-off for all observers, only six false-negative and one false-positive ratings occurred in total (AUCROC 0.99±0.01). Inter-observer agreement was good for VRP

  12. An Improved FP-Growth with Hybrid MGSO-IRVM Classifier Approach used for Type-2 Diabetes Mellitus Diagnosis

    Directory of Open Access Journals (Sweden)

    K.Vembandasamy

    2015-12-01

    Full Text Available Diabetes is a chronic disease and major problem of morbidity and mortality in developing countries. Type-2 diabetes mellitus (T2DM is the most common type of diabetes and accounts for 90- 95% of all diabetes. In the medical field a predictive data mining association algorithms is used to diagnose the disease at the earlier stage which helps the physicians in the treatment planning procedure. Recently, an improved Frequent Pattern Growth (IFP-Growth with Hybrid Enhanced Artificial Bee Colony-Advanced Kernel Support Vector Machine (EABC-AKSVM classification is introduced with the capability to reduce the number of rules in diagnosing the diabetes. However, the detection accuracy and robust is less. To resolve this problem, an Improved Frequent Pattern Growth (IFP-Growth with Hybrid Modified Glowworm Swarm Optimization-Improved Relevance Vector Machine (MGSO-IRVM Classification based Association Rule Mining (ARM system is proposed in this work to generate effective rules. The proposed work consists of two phases: In first phase, improved FP-growth is proposed to efficiently mine frequent patterns even from uncertain medical database. This is achieved by creating additional array for each item in uncertain transactional database to keep the information of its superitem sets in IFP-tree redundant node generation through this step the computational cost is greatly reduced. In next phase, Hybrid MGSO-IRVM classifier is used to generate the association rules based on the frequent item sets, which avoids rule redundancy and conflicts during the rule mining process. Experimental results show that the proposed model is suitable and alternative model for medical classification to achieve greater accuracy, and to improve medical diagnosis.

  13. Hypoxia monitoring activities within the FP7 EU-project HYPOX: diverse approaches to understand a complex phenomenon

    Science.gov (United States)

    Janssen, F.; Waldmann, C.; Boetius, A.

    2012-04-01

    Hypoxic conditions in aquatic systems and the occurrence of 'dead zones' increase worldwide due to man-made eutrophication and global warming with consequences for biodiversity, ecosystem functions and services such as fisheries, aquaculture and tourism. Monitoring of hypoxia and its consequences has to (1) account for the appropriate temporal and spatial scales, (2) separate anthropogenic from natural drivers and long-term trends from natural variations, (3) assess ecosystem response, (4) use modeling tools for generalization and prediction, and (5) share data and obtained knowledge. In 2009 the EU FP7 project HYPOX (www.hypox.net) started out as a pioneering attempt to improve and integrate hypoxia observation capacities addressing these requirements. Target ecosystems selected for HYPOX cover a broad range of settings (e.g., hydrography, oxygenation status, biological activity, anthropogenic impact) and differ in their sensitivity towards change. Semi-enclosed basins with permanent anoxia (Black Sea, Baltic Sea), are included as well as seasonally or locally hypoxic land-locked systems (fjords, lagoons, lakes) and open ocean systems with high sensitivity to global warming (North Atlantic - Arctic transition). Adopted monitoring approaches involve autonomous, cabled, and shipboard instruments and include static and profiling moorings, benthic observatories, drifters, as well as classical CTD surveys. In order to improve observatory performance, project activities encompass developments of oxygen sensors as well as calibration procedures and technologies to reduce biofouling. Modeling and data assimilation are used to synthesize findings, to obtain an in-depth understanding of hypoxia causes and consequences, and to improve forecasting capacities. For integration of the collected information into a global oxygen observing system, results are disseminated through the HYPOX portal following GEOSS data sharing principles. This presentation will give an overview of

  14. Correlation between neuromelanin-sensitive MR imaging and {sup 123}I-FP-CIT SPECT in patients with parkinsonism

    Energy Technology Data Exchange (ETDEWEB)

    Kuya, Keita; Shinohara, Yuki; Miyoshi, Fuminori; Fujii, Shinya; Tanabe, Yoshio; Ogawa, Toshihide [Tottori University, Division of Radiology, Department of Pathophysiological Therapeutic Science, Faculty of Medicine, Yonago (Japan)

    2016-04-15

    Neuromelanin-sensitive MR imaging (MRI) can visualize neuromelanin-containing neurons in the substantia nigra pars compacta (SNc), and its utility has been reported in the evaluation of parkinsonism. Conversely, dopamine transporter imaging by {sup 123}I-N-v-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl)nortropane (FP-CIT) SPECT (DaTSCAN) is now an established method for evaluating parkinsonism, detecting presynaptic dopamine neuronal dysfunction. Both methods can assist differentiating neurodegenerative and other forms of parkinsonism. However, to our knowledge, there have been no studies concerning a correlation between the two methods. The aim of this study was to assess the utility of neuromelanin-sensitive MRI for diagnosing parkinsonism by examining a correlation with DaTSCAN. Twenty-three patients with parkinsonism who underwent both neuromelanin-sensitive MRI and DaTSCAN were included. We measured the neuromelanin-positive SNc region volume by manually contouring the high signal intensity region of the SNc on neuromelanin-sensitive MRI and measured the specific binding ratio (SBR) on DaTSCAN. The asymmetry index of neuromelanin-positive SNc volume and the asymmetry index of SBR were also calculated. The volume of the neuromelanin-positive SNc region showed significant correlation with specific binding ratio (SBR) (right P <.001, ρ = 0.78, left P <.001, ρ = 0.86). The asymmetry index of neuromelanin-positive SNc volume also showed significant correlations with the asymmetry index of SBR (P <.001, ρ = 0.73). Decrease of the high signal intensity region of the SNc on neuromelanin-sensitive MRI would indicate damage to the nigrostriatal dopaminergic function as well as loss of dopaminergic neurons. We conclude that neuromelanin-sensitive MRI is a useful diagnostic biomarker for parkinsonism. (orig.)

  15. 123I-FP-CIT SPECT imaging in early diagnosis of dementia in patients with and without a vascular component

    Directory of Open Access Journals (Sweden)

    Marina eGarriga

    2015-07-01

    Full Text Available Alzheimer’s disease (AD and vascular dementia (VaD are the most common cause of dementia. Cerebral ischemia is a major risk factor for development of dementia. 123I-FP-CIT SPECT (DaTScan is a complementary tool in the differential diagnoses of patients with incomplete or uncertain Parkinsonism. Additional application of DaTScan enables the categorization of Parkinsonian disease with dementia (PDD, and its differentiation from pure AD, and may further contribute to change the therapeutic decision. The aim of this study was to analyse the vascular contribution towards dementia and mild cognitive impairment (MCI. We evaluated the utility of DaTScan for the early diagnosis of dementia in patients with and without a clinical vascular component, and the association between neuropsychological function, vascular component and dopaminergic function on DaTScan. 105 patients with MCI or the initial phases of dementia were studied prospectively. We developed an initial assessment using neurologic examination, blood tests, cognitive function tests, structural neuroimaging and DaTScan. The vascular component was later quantified in two ways: clinically, according to the Framingham Risk Score and by structural neuroimaging using Wahlund Scale Total Score (WSTS. Early diagnosis of dementia was associated with an abnormal DaTScan. A significant association was found between a high WSTS and an abnormal DaTScan (p<0.01. Mixed AD was the group with the highest vascular component, followed by the VaD group, while MCI and pure AD showed similar WSTS. No significant associations were found between neuropsychological impairment and DaTScan independently of associated vascular component. DaTScan seems to be a good tool to discriminate, in a first clinical assessment, patients with MCI from those with established dementia. There was bigger general vascular affectation observable in MRI or CT in patients with abnormal dopaminergic uptake seen on DaTScan.

  16. Calibration of gamma camera systems for a multicentre European {sup 123}I-FP-CIT SPECT normal database

    Energy Technology Data Exchange (ETDEWEB)

    Tossici-Bolt, Livia [Southampton Univ. Hospitals NHS Trust, Dept. of Medical Physics and Bioengineering, Southampton (United Kingdom); Dickson, John C. [UCLH NHS Foundation Trust and Univ. College London, Institute of Nuclear Medicine, London (United Kingdom); Sera, Terez [Univ. of Szeged, Dept. of Nuclear Medicine and Euromedic Szeged, Szeged (Hungary); Nijs, Robin de [Rigshospitalet and Univ. of Copenhagen, Neurobiology Research Unit, Copenhagen (Denmark); Bagnara, Maria Claudia [Az. Ospedaliera Universitaria S. Martino, Medical Physics Unit, Genoa (Italy); Jonsson, Cathrine [Karolinska Univ. Hospital, Dept. of Nuclear Medicine, Medical Physics, Stockholm (Sweden); Scheepers, Egon [Univ. of Amsterdam, Dept. of Nuclear Medicine, Academic Medical Centre, Amsterdam (Netherlands); Zito, Felicia [Fondazione IRCCS Granda, Ospedale Maggiore Policlinico, Dept. of Nuclear Medicine, Milan (Italy); Seese, Anita [Univ. of Leipzig, Dept. of Nuclear Medicine, Leipzig (Germany); Koulibaly, Pierre Malick [Univ. of Nice-Sophia Antipolis, Nuclear Medicine Dept., Centre Antoine Lacassagne, Nice (France); Kapucu, Ozlem L. [Gazi Univ., Faculty of Medicine, Dept. of Nuclear Medicine, Ankara (Turkey); Koole, Michel [Univ. Hospital and K.U. Leuven, Nuclear Medicine, Leuven (Belgium); Raith, Maria [Medical Univ. of Vienna, Dept. of Nuclear Medicine, Vienna (Austria); George, Jean [Univ. Catholique Louvain, Nuclear Medicine Division, Mont-Godinne Medical Center, Mont-Godinne (Belgium); Lonsdale, Markus Nowak [Bispebjerg Univ. Hospital, Dept. of Clinical Physiology and Nuclear Medicine, Copenhagen (Denmark); Muenzing, Wolfgang [Univ. of Munich, Dept. of Nuclear Medicine, Munich (Germany); Tatsch, Klaus [Univ. of Munich, Dept. of Nuclear Medicine, Munich (Germany); Municipal Hospital of Karlsruhe Inc., Dept. of Nuclear Medicine, Karlsruhe (Germany); Varrone, Andrea [Center for Psychiatric Research, Karolinska Inst., Dept. of Clinical Neuroscience, Stockholm (Sweden)

    2011-08-15

    A joint initiative of the European Association of Nuclear Medicine (EANM) Neuroimaging Committee and EANM Research Ltd. aimed to generate a European database of [{sup 123}I]FP-CIT single photon emission computed tomography (SPECT) scans of healthy controls. This study describes the characterization and harmonization of the imaging equipment of the institutions involved. {sup 123}I SPECT images of a striatal phantom filled with striatal to background ratios between 10:1 and 1:1 were acquired on all the gamma cameras with absolute ratios measured from aliquots. The images were reconstructed by a core lab using ordered subset expectation maximization (OSEM) without corrections (NC), with attenuation correction only (AC) and additional scatter and septal penetration correction (ACSC) using the triple energy window method. A quantitative parameter, the simulated specific binding ratio (sSBR), was measured using the ''Southampton'' methodology that accounts for the partial volume effect and compared against the actual values obtained from the aliquots. Camera-specific recovery coefficients were derived from linear regression and the error of the measurements was evaluated using the coefficient of variation (COV). The relationship between measured and actual sSBRs was linear across all systems. Variability was observed between different manufacturers and, to a lesser extent, between cameras of the same type. The NC and AC measurements were found to underestimate systematically the actual sSBRs, while the ACSC measurements resulted in recovery coefficients close to 100% for all cameras (AC range 69-89%, ACSC range 87-116%). The COV improved from 46% (NC) to 32% (AC) and to 14% (ACSC) (p < 0.001). A satisfactory linear response was observed across all cameras. Quantitative measurements depend upon the characteristics of the SPECT systems and their calibration is a necessary prerequisite for data pooling. Together with accounting for partial volume, the

  17. Neutralization of improvised explosive devices by high-power lasers: research results from the FP7 project ENCOUNTER

    Science.gov (United States)

    Osterholz, J.; Lueck, M.; Lexow, B.; Wickert, M.

    2016-10-01

    The development of reliable techniques for the safe neutralization of improvised explosive devices (IEDs) is an active field of research. Recently, innovative approaches for the neutralization of IEDs were developed and tested within the FP7 project ENCOUNTER ("Explosive Neutralisation and Mitigation Countermeasures for IEDs in Urban/Civil Environment") and were compared to existing, established technologies. Here, the ENCOUNTER project is presented with a special focus on the neutralization of IEDs by high-power lasers. The working principle of the application of high-power lasers for the neutralization of explosive devices is based on thermal effects. Heating of the IEDs main charge may occur either by direct irradiation of the explosive material or by heat transfer through the main charge's confinement. The aim of the application of the laser is to achieve a low order burning reaction of the explosive charge and thus a controlled neutralization of the IED. Since laser beams allow for the directed transport of energy, this technique can be applied over long stand-off distances and has thus potential for an increase of the safety of clearing forces and population in the case of terroristic attacks in a civilian environment. Within the ENCOUNTER project, a laboratory environment has been set up which allows for the irradiation of IEDs with a laser power of up to 10 kW. Experiments have been carried out on a broad spectrum of different types of IEDs. The processes during neutralization were studied in detail with high-speed diagnostics. On the basis of these experimental data, the safety and the reliability of the application of the laser was analyzed, and recommendations to end users were given. In addition to the results of the ENCOUNTER project, approaches for the numerical simulation of the neutralization of IEDs are discussed.

  18. An optical pulse width modulation generator based on the injection-locking property of single mode FP-LD

    Science.gov (United States)

    Tran, Quoc Hoai; Nakarmi, Bikash; Won, Yong Hyub

    2013-03-01

    A novel simple optical pulse width modulation generator (OPWMG) based on injection-locking property of a single mode FP-LD (SMFP-LD) has been proposed and experimentally verified. The OPWMG consists of a SMFP-LD (which acts as comparator), an optical sinusoidal wave source (analog input), and a continuous optical beam (control signal). The power required for fully injection-locking the SMFP-LD acts as the referent power whereas the combination power of continuous optical beam and analog optical sinusoidal signals work as control signals for changing the duty cycle of the proposed OPWMG. The presence of only continuous optical beam is not sufficient to suppress the dominant mode of SMFP-LD with high ON/OFF contrast ratio; however, the application of additional sinusoidal wave of constant amplitude and frequency, the dominant mode of SMFP-LD can be suppressed for the certain time window. Since, injection-locking power is dependent with the combined power of input injected continuous beam and sinusoidal optical wave, the time window of injection-locking can be varied by changing input beam power which provides different duty cycle of 13% to 68% at the output. Current available schemes for generating PWM signals are in electrical domain, hence, they need to convert electrical signals into optical domain by using expensive O/E converters for application in optical control and signal processing. The proposed OPWMG scheme has several advantages, such as low cost, low power consumption (~0.5 mW) which can be used for various applications where the effect of EMI/EMR is considered as an important factor such as control circuit for high voltage converters in power plant and electrical vehicles.

  19. Difluoro-lambda(5)-phosphinonitrile F(2)P[triple bond]N: matrix isolation and photoisomerization into FP=NF.

    Science.gov (United States)

    Zeng, Xiaoqing; Beckers, Helmut; Willner, Helge

    2009-01-01

    Splendid isolation: Monomeric phosphazene F(2)PN ((1)A(1)) was prepared for the first time through irradiation of F(2)PN(3) in an argon matrix with an ArF excimer laser (lambda=193 nm). Upon subsequent irradiation with a high-pressure mercury arc lamp (lambda=255 nm), F(2)PN undergoes a 1,2-fluorine shift to give iminophosphane cis-FP=NF.

  20. The Italian forest sites of FunDivEUROPE: a new FP7 project on the functional significance of forest biodiversity in Europe

    OpenAIRE

    Bussotti F; Coppi A; Pollastrini M; Feducci M; Baeten L; Scherer-Lorenzen M.; Verheyen K; Selvi F

    2012-01-01

    The Italian forest sites of FunDivEUROPE: a new FP7 project on the functional significance of forest biodiversity in Europe. FunDivEUROPE is a new project aiming at a deeper understanding of the role of forest diversity on ecosystem functions and service provisioning for society. This project combines three scientific platforms: experimental, exploratory and inventory. The exploratory platform is based on the observation of a broad range of properties, traits and ecological processes on a net...

  1. Prostaglandin receptor EP2 in the crosshairs of anti-inflammation, anti-cancer, and neuroprotection.

    Science.gov (United States)

    Jiang, Jianxiong; Dingledine, Ray

    2013-07-01

    Modulation of a specific prostanoid synthase or receptor provides therapeutic alternatives to nonsteroidal anti-inflammatory drugs (NSAIDs) for treating pathological conditions governed by cyclooxygenase-2 (COX-2 or PTGS2). Among the COX-2 downstream signaling pathways, the prostaglandin E2 (PGE2) receptor EP2 subtype (PTGER2) is emerging as a crucial mediator of many physiological and pathological events. Genetic ablation strategies and recent advances in chemical biology provide tools for a better understanding of EP2 signaling. In the brain, the EP2 receptor modulates some beneficial effects, including neuroprotection, in acute models of excitotoxicity, neuroplasticity, and spatial learning via cAMP-PKA signaling. Conversely, EP2 activation accentuates chronic inflammation mainly through the cAMP-Epac pathway, likely contributing to delayed neurotoxicity. EP2 receptor activation also engages β-arrestin in a G-protein-independent pathway that promotes tumor cell growth and migration. Understanding the conditions under which multiple EP2 signaling pathways are engaged might suggest novel therapeutic strategies to target this key inflammatory prostaglandin receptor.

  2. Prostaglandin E2 and the EP receptors in malignancy: possible therapeutic targets?

    Science.gov (United States)

    O'Callaghan, G

    2015-01-01

    Abstract Elevated expression of COX‐2 and increased levels of PGE2 are found in numerous cancers and are associated with tumour development and progression. Although epidemiological, clinical and preclinical studies have shown that the inhibition of PGE2 synthesis through the use of either non‐steroidal anti‐inflammatory drugs (NSAIDs) or specific COX‐2 inhibitors (COXibs) has the potential to prevent and treat malignant disease, toxicities due to inhibition of COX‐2 have limited their use. Thus, there is an urgent need for the development of strategies whereby COX‐2 activity may be reduced without inducing any side effects. The biological effects of PGE2 are mediated by signalling through four distinct E‐type prostanoid (EP) receptors – EP1, EP2, EP3 and EP4. In recent years, extensive effort has gone into elucidating the function of PGE2 and the EP receptors in health and disease, with the goal of creating selective inhibitors as a means of therapy. In this review, we focus on PGE2, and in particular on the role of the individual EP receptors and their signalling pathways in neoplastic disease. As knowledge concerning the role of the EP receptors in cancer grows, so does the potential for exploiting the EP receptors as therapeutic targets for the treatment of cancer and metastatic disease. PMID:26377664

  3. Oxygen transfer coefficient and the kinetic parameters of exo-polygalacturonase production by Aspergillus flavipes FP-500 in shake flasks and bioreactor.

    Science.gov (United States)

    Gómez Sánchez, C E; Martínez-Trujillo, A; Aguilar Osorio, G

    2012-12-01

    To evaluate and compare the sensitivity of Exo-PG production and kinetic parameters of Aspergillus flavipes FP-500 to oxygen transfer condition in shake flasks and bioreactor. Aspergillus flavipes FP-500 was grown on pectin as carbon source in shake flasks and bioreactor at different oxygen transfer conditions. The volumetric coefficient of oxygen transfer (kLa) was modified by changing both, the flask size/medium volume ratio and the agitation speed. Higher biomass concentration, Exo-PG activity, maximum specific growth rate and yield coefficient were obtained in bioreactor at higher kLa value. A strong correlation was found between biomass, Exo-PG activity and growth-associated product coefficient to kLa in bioreactor but does not in shake flasks. The mathematical model provided a good description of growth, pectin consumption and Exo-PG production in submerged batch cultures carried out in bioreactor. Biomass concentration, Exo-PG activity and their kinetics of Aspergillus flavipes FP-500 were strongly influenced by oxygen transfer condition and cultivation system. Significance and Impact of Study The production of enzymes by fungal fermentation is strictly aerobic and understanding the influence of oxygen transfer condition on the production kinetic is of vital importance in order to design, optimize and translate bioprocesses to industrial scale. © 2012 The Society for Applied Microbiology.

  4. Projects and potentialities for Scientific and Technological Cooperation between Mexico and Thailand under the European Union's Seventh Framework Program (FP7: 2007-2013

    Directory of Open Access Journals (Sweden)

    Jürgen Haberleithner

    2012-09-01

    Full Text Available The European Union and Mexico have been cooperating in the field of R&D since the partnership treaty between the Eu and Mexico took effect in 2000. With the Lisbon Strategy put into operation that same year, Europe acknowledged the central role which will be played by knowledge in the economy and society of the future. Accordingly, innovation was emphasized in order to advance mutual efforts to establish innovative research and development projects with Third Countries such as Mexico and Thailand through diverse multilateral framework programs such as the Seventh Framework Program (Fp7. A brief evaluation of the existing projects in Fp7 reveal disposition for intraregional cooperation in spite of the disparities regarding the quantity and extension of projects. Moreover, studied participants share a similar lack of know-how for coordinating projects which is at times crucial for benefiting completely from the program. Potential exists for establishing the necessary links and coordinating points amongst Mexico and Thailand under the given cooperation regional and bilateral mechanisms and the extensive research areas that the program covers. It is these specific potentialities enabled by the Fp7 in both regions that intend to be further researched for their development into multiple and successful projects.

  5. Diagnostic accuracy of Parkinson disease by support vector machine (SVM) analysis of 123I-FP-CIT brain SPECT data: implications of putaminal findings and age.

    Science.gov (United States)

    Palumbo, Barbara; Fravolini, Mario Luca; Buresta, Tommaso; Pompili, Filippo; Forini, Nevio; Nigro, Pasquale; Calabresi, Paolo; Tambasco, Nicola

    2014-12-01

    Brain single-photon-emission-computerized tomography (SPECT) with I-ioflupane (I-FP-CIT) is useful to diagnose Parkinson disease (PD). To investigate the diagnostic performance of I-FP-CIT brain SPECT with semiquantitative analysis by Basal Ganglia V2 software (BasGan), we evaluated semiquantitative data of patients with suspect of PD by a support vector machine classifier (SVM), a powerful supervised classification algorithm.I-FP-CIT SPECT with BasGan analysis was performed in 90 patients with suspect of PD showing mild symptoms (bradykinesia-rigidity and mild tremor). PD was confirmed in 56 patients, 34 resulted non-PD (essential tremor and drug-induced Parkinsonism). A clinical follow-up of at least 6 months confirmed diagnosis. To investigate BasGan diagnostic performance we trained SVM classification models featuring different descriptors using both a "leave-one-out" and a "five-fold" method. In the first study we used as class descriptors the semiquantitative radiopharmaceutical uptake values in the left (L) and right (R) putamen (P) and in the L and R caudate nucleus (C) for a total of 4 descriptors (CL, CR, PL, PR). In the second study each patient was described only by CL and CR, while in the third by PL and PR descriptors. Age was added as a further descriptor to evaluate its influence in the classification performance.I-FP-CIT SPECT with BasGan analysis reached a classification performance higher than 73.9% in all the models. Considering the "Leave-one-out" method, PL and PR were better predictors (accuracy of 91% for all patients) than CL and CR descriptors; using PL, PR, CL, and CR diagnostic accuracy was similar to that of PL and PR descriptors in the different groups. Adding age as a further descriptor accuracy improved in all the models. The best results were obtained by using all the 5 descriptors both in PD and non-PD subjects (CR and CL + PR and PL + age = 96.4% and 94.1%, respectively). Similar results were observed for the "five

  6. Clinical correlation of the binding potential with {sup 123}I-FP-CIT in de novo idiopathic Parkinson's disease patients

    Energy Technology Data Exchange (ETDEWEB)

    Berti, Valentina; Pupi, Alberto; Vanzi, Eleonora; Cristofaro, Maria Teresa de; Pellicano, Giannantonio; Mungai, Francesco [University of Florence, Clinical Pathophysiology, Florence (Italy); Ramat, Silvia; Marini, Paolo; Sorbi, Sandro [University of Florence, Neurological and Psychiatric Sciences, Florence (Italy)

    2008-12-15

    The aim of this study was to evaluate the accuracy of different single-photon emission computed tomography (SPECT) reconstruction techniques in measuring striatal N-{omega}-fluoropropyl-2{beta}-carbomethoxy-3{beta}-4-[{sup 123}I]iodophenyl-nortropane ({sup 123}I-FP-CIT) binding in de novo Parkinson's disease (PD) patients, in order to find a correlation with clinical scales of disease severity in the initial phases of disease. Thirty-six de novo PD patients underwent {sup 123}I-FP-CIT SPECT and MRI scan. SPECT data were reconstructed with filtered back projection (FBP), with an iterative algorithm (ordered subset expected maximization, OSEM) and with a method previously developed in our institution, called least-squares (LS) method. The ratio of specific to non-specific striatal {sup 123}I-FP-CIT binding (binding potential, BP) was used as the outcome measure with all the reconstruction methods (BP{sub FBP}, BP{sub OSEM}, BP{sub LS}). The range of values of striatal BP{sub LS} was significantly greater than BP{sub FBP} and BP{sub OSEM}. For all striatal regions, estimates of BP{sub FBP} correlated well with BP{sub OSEM} (r=0.84) and with BP{sub LS} (r=0.64); BP{sub OSEM} correlated significantly with BP{sub LS} (r=0.76). A good correlation was found between putaminal BP{sub LS} and Hoen and Yahr, Unified PD Rating Scale (UPDRS) and lateralized UPDRS motor scores (r=-0.46, r=-0.42, r=-0.39, respectively). Neither putaminal BP{sub FBP} nor putaminal BP{sub OSEM} correlated with any of these motor scores. In de novo PD patients, {sup 123}I-FP-CIT BP values derived from FBP and OSEM reconstruction techniques do not permit to differentiate PD severity. The LS method instead finds a correlation between striatal BP and disease severity scores. The results of this study support the use of {sup 123}I-FP-CIT BP values estimated with the LS method as a biomarker of PD severity. (orig.)

  7. Astrobiology Road Mapping (AstRoMap) - A project within FP7 of the European Commission: First results

    Science.gov (United States)

    Gomez-Gomez, Felipe; Capria, Maria Teresa; Palomba, Ernesto; Walter, Nicolas; Rettberg, Petra; Muller, Christian; Horneck, Gerda

    AstRoMap (Astrobiology and Planetary Exploration Road Mapping) is a funded project formulated in the 5th Call of the European Commission FP7 framework. The main objectives of the AstRoMap are: 1. Identify the main astrobiology issues to be addressed by Europe in the next decades in relation with space exploration 2. Identify potential mission concepts that would allow addressing these issues 3. Identify the technology developments required to enable these missions 4. Provide a prioritized roadmap integrating science and technology activities as well as ground-based approach 5. Map scientific knowledge related to astrobiology in Europe To reach those objectives, AstRoMap is executed within the following steps: 1. Community consultation. In order to map the European astrobiology landscape and to provide a collaborative networking platform for this community, the AstRoMap project hosts a database of scientists (European and beyond) interested in astrobiology and planetary exploration (see: http://www.astromap.eu/database.html). It reflects the demography and the research and teaching activities of the astrobiology community, as well as their professional profiles and involvement in astrobiology projects. Considering future aspects of astrobiology in Europe, the need for more astrobiology-dedicated funding programmes at the EU level, especially for cross-disciplinary groups, was stressed. This might eventually lead to the creation of a European laboratory of Astrobiology, or even of a European Astrobiology Institute. 2. Workshops organisation. On the basis of the feedbacks from the community consultation, the potential participants and interesting topics are being identified to take part in the following workshops: 1-. Origin of organic compounds, steps to life; 2. Physico-chemical boundary conditions for habitability 3. Biosignatures as facilitating life detection 4. Origin of the Solar system 3. Astrobiology road-mapping. Based on the results and major conclusions

  8. Formación continua en centros de FP y actividades de innovación en las Pymes industriales

    Directory of Open Access Journals (Sweden)

    Lavía, Cristina

    2012-02-01

    Full Text Available The current economic crisis is affecting Spain with special force. Within that context, the relationships between the education system and the economic system become a key issue. The aim of this paper is to make a contribution to the understanding of the relationships between vocational training (VT centres and small and medium-sized firms (SMEs. Our study is based on a survey of industrial SMEs from two Northern Spanish autonomous communities (Basque Country and Navarre. The different types of SME-VT centre relationship are analyzed, and special attention if devoted to new forms of relationships among those agents (mainly continuous training, and to the possible effects of SME-VT centre collaboration upon the firms’ innovation processes. We show that, right now, continuous training activities are a key form of relationship between VT centres and SMEs. That type of relationship acquires an strategic importance from the point of view of the coordination between the training system and the innovation system.

    La crisis actual, que afecta con especial virulencia a España, obliga a reflexionar sobre las relaciones entre el sistema educativo y el sistema económico. En este trabajo, basado en una encuesta a pequeñas y medianas empresas industriales de las comunidades autónomas vasca y navarra, se pretende avanzar en el conocimiento de las relaciones entre los centros de Formación Profesional y las empresas. Se prestará especial atención a las nuevas formas de relación entre ambos agentes (especialmente la formación continua, y al efecto que la colaboración con los centros de FP pueda tener sobre los procesos de innovación de las empresas. Se muestra que, en la actualidad, las actividades de formación continua constituyen una forma de colaboración importante para las empresas y estratégica desde el punto de vista del ajuste entre el sistema de formación y el sistema de innovación.

  9. The ISS SOLAR payload data preservation in the frame of the PERICLES FP-7 project: metadata aspects.

    Science.gov (United States)

    Muller, Christian; Pandey, Praveen

    2016-04-01

    PERICLES (Promoting and Enhancing the Reuse of Information throughout the Content Lifecycle exploiting Evolving Semantics) is an FP7 project started on February 2013. It aims at preserving by design large and complex data sets. PERICLES is coordinated by King's College London, UK and its partners are University of Borås (Sweden), CERTH- ITI (Greece), DotSoft (Greece), Georg-August-Universität Göttingen (Germany), University of Liverpool (UK), Space Application Services (Belgium), XEROX France and University of Edinburgh (UK). Two additional partners provide the two case studies: Tate Gallery (UK) brings the digital art and media case study and B.USOC (Belgian Users Support and Operations Centre) brings the space science case study . PERICLES addresses the life-cycle of large and complex data sets in order to cater for the evolution of context of data sets and user communities, including groups unanticipated when the data was created. Semantics of data sets are thus also expected to evolve and the project includes elements which could address the reuse of data sets at periods where the data providers and even their institutions are not available any more. PERICLES uses the Linked Resources Model (LRM) which will be compared with the OAIS standard. In this study we present the space science case associated with PERICLES. B.USOC supports experiments on the International Space Station and is the curator of the collected data and operations history. B.USOC has chosen to analyse the SOLAR payload flying since 2008 on the ESA COLUMBUS module of the ISS as the PERICLES prime space science case. Solar observation data are prime candidates for long term data preservation as variabilities of the solar spectral irradiance have an influence on earth climate. The nature of the data to be preserved for the reuse of the current SOLAR series is much more extended than a simple set of time tagged tables of spectral irradiances, it is an important inventory of more than 50 classes

  10. Endogenous prostaglandin E2 amplifies IL-33 production by macrophages through an E prostanoid (EP)2/EP4-cAMP-EPAC-dependent pathway.

    Science.gov (United States)

    Samuchiwal, Sachin K; Balestrieri, Barbara; Raff, Hannah; Boyce, Joshua A

    2017-05-19

    When activated through toll-like receptors (TLRs), macrophages generate IL-33, an IL-1 family member that induces innate immune responses through ST2 signaling. LPS, a TLR4 ligand, induces macrophages to generate prostaglandin E2 (PGE2) through inducible COX-2 and microsomal PGE2 synthase 1 (mPGES-1) (1). We demonstrate that IL-33 production by bone marrow-derived murine macrophages (bmMFs) requires the generation of endogenous PGE2 and the intrinsic expression of EP2 receptors to amplify NF-κB-dependent, LPS-induced IL-33 expression via exchange protein activated by cAMP (EPAC). Compared with WT cells, bmMFs lacking either mPGES-1 or EP2 receptors displayed reduced LPS-induced IL-33 levels. A selective EP2 agonist and, to a lesser extent, EP4 receptor agonist potentiated LPS-induced IL-33 generation from both mPGES-1-null and WT bmMFs, whereas EP1 and EP3 receptor agonists were inactive. The effects of PGE2 depended on cAMP, were mimicked by an EPAC-selective agonist, and were attenuated by EPAC-selective antagonism and knockdown. LPS-induced p38 MAPK and NF-κB activations were necessary for both IL-33 production and PGE2 generation, and exogenous PGE2 partly reversed the suppression of IL-33 production caused by p38 MAPK and NF-κB inhibition. Mice lacking mPGES-1 showed lower IL-33 levels and attenuated lung inflammation in response to repetitive Alternaria inhalation challenges. Cumulatively, our data demonstrate that endogenous PGE2, EP2 receptors, and EPAC are prerequisites for maximal LPS-induced IL-33 expression and that exogenous PGE2 can amplify IL-33 production via EP2 and EP4 receptors. The ubiquitous induction of mPGES-1-dependent PGE2 may be crucial for innate immune system activation during various IL-33 driven pathologic disorders. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. EP2 receptor mediates PGE2-induced cystogenesis of human renal epithelial cells.

    Science.gov (United States)

    Elberg, Gerard; Elberg, Dorit; Lewis, Teresa V; Guruswamy, Suresh; Chen, Lijuan; Logan, Charlotte J; Chan, Michael D; Turman, Martin A

    2007-11-01

    Autosomal-dominant polycystic kidney disease (ADPKD) is characterized by formation of cysts from tubular epithelial cells. Previous studies indicate that secretion of prostaglandin E2 (PGE2) into cyst fluid and production of cAMP underlie cyst expansion. However, the mechanism by which PGE2 directly stimulates cAMP formation and modulates cystogenesis is still unclear, because the particular E-prostanoid (EP) receptor mediating the PGE2 effect has not been characterized. Our goal is to define the PGE2 receptor subtype involved in ADPKD. We used a three-dimensional cell-culture system of human epithelial cells from normal and ADPKD kidneys in primary cultures to demonstrate that PGE2 induces cyst formation. Biochemical evidence gathered by using real-time RT-PCR mRNA analysis and immunodetection indicate the presence of EP2 receptor in cystic epithelial cells in ADPKD kidney. Pharmacological evidence obtained by using PGE2-selective analogs further demonstrates that EP2 mediates cAMP formation and cystogenesis. Functional evidence for a role of EP2 receptor in mediating cAMP signaling was also provided by inhibiting EP2 receptor expression with transfection of small interfering RNA in cystic epithelial cells. Our results indicate that PGE2 produced in cyst fluid binds to adjacent EP2 receptors located on the apical side of cysts and stimulates EP2 receptor expression. PGE2 binding to EP2 receptor leads to cAMP signaling and cystogenesis by a mechanism that involves protection of cystic epithelial cells from apoptosis. The role of EP2 receptor in mediating the PGE2 effect on stimulating cyst formation may have direct pharmacological implications for the treatment of polycystic kidney disease.

  12. Multiple roles of the PGE2 -EP receptor signal in vascular permeability.

    Science.gov (United States)

    Omori, K; Kida, T; Hori, M; Ozaki, H; Murata, T

    2014-11-01

    PGE2 is a major prostanoid that regulates inflammation by stimulating EP1-4 receptors. However, how PGE2 induces an initial inflammatory response to vascular hyper-permeability remains unknown. Here we investigated the role of the PGE2 -EP receptor signal in modulating vascular permeability both in vivo and in vitro. We used a modified Miles assay and intravital microscopy to examine vascular permeability in vivo. Endothelial barrier property was assessed by measuring transendothelial electrical resistance (TER) in vitro. Local administration of PGE2 , an EP2 or EP4 receptor agonist into FVB/NJcl mouse ear skin caused vascular leakage, indicated by dye extravasation. Intravital microscopy and laser Doppler blood-flow imaging revealed that these treatments dilated peripheral vessels and increased local blood flow. Pretreatment with the vasoconstrictor phenylephrine inhibited the PGE2 -induced blood flow increase and vascular leakage. In contrast to the EP2 and EP4 receptor agonists, administration of an EP3 receptor agonist suppressed vascular leakage without altering vascular diameter or blood flow. In isolated HUVECs, the EP3 receptor agonist elevated TER and blocked thrombin-induced dextran passage. Inhibiting PKA restored the hypo-permeability induced by the EP3 receptor agonist. Activation of the PGE2 -EP2 or -EP4 receptor signal induces vasodilatation in mural cells, resulting in increased local blood flow and hyper-permeability. In contrast, activation of the PGE2 -EP3 receptor signal induces a cAMP-dependent enhancement of the endothelial barrier, leading to hypo-permeability. We provide the first evidence that endothelial cells and mural cells cooperate to modulate vascular permeability. © 2014 The British Pharmacological Society.

  13. Framework Collaboration Agreement with the Institute of Physics Belgrade (IPB) Dr. Alexandar Belic Framework Collaboration Agreement with the Faculty of Physics of University of Belgrade (FP-UB) Prof. Petar Adzic

    CERN Multimedia

    Pantelia, Anna

    2014-01-01

    Framework Collaboration Agreement with the Institute of Physics Belgrade (IPB) Dr. Alexandar Belic Framework Collaboration Agreement with the Faculty of Physics of University of Belgrade (FP-UB) Prof. Petar Adzic

  14. Inflammatory Eicosanoids Increase Amyloid Precursor Protein Expression via Activation of Multiple Neuronal Receptors.

    Science.gov (United States)

    Herbst-Robinson, Katie J; Liu, Li; James, Michael; Yao, Yuemang; Xie, Sharon X; Brunden, Kurt R

    2015-12-17

    Senile plaques comprised of Aβ peptides are a hallmark of Alzheimer's disease (AD) brain, as are activated glia that release inflammatory molecules, including eicosanoids. Previous studies have demonstrated that amyloid precursor protein (APP) and Aβ levels can be increased through activation of thromboxane A2-prostanoid (TP) receptors on neurons. We demonstrate that TP receptor regulation of APP expression depends on Gαq-signaling and conventional protein kinase C isoforms. Importantly, we discovered that Gαq-linked prostaglandin E2 and leukotriene D4 receptors also regulate APP expression. Prostaglandin E2 and thromboxane A2, as well as total APP levels, were found to be elevated in the brains of aged 5XFAD transgenic mice harboring Aβ plaques and activated glia, suggesting that increased APP expression resulted from eicosanoid binding to Gαq-linked neuronal receptors. Notably, inhibition of eicosanoid synthesis significantly lowered brain APP protein levels in aged 5XFAD mice. These results provide new insights into potential AD therapeutic strategies.

  15. Serotonin transporters in dopamine transporter imaging: a head-to-head comparison of dopamine transporter SPECT radioligands 123I-FP-CIT and 123I-PE2I

    DEFF Research Database (Denmark)

    Ziebell, Morten; Holm-Hansen, Signe; Thomsen, Gerda

    2010-01-01

    the SPECT radioligands (123)I-2-β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)nortropane ((123)I-FP-CIT) and (123)I-N-(3-iodoprop-2E-enyl)-2-β-carbomethoxy-3β-(4-methylphenyl) nortropane ((123)I-PE2I), which has a 10-fold higher selectivity than (123)I-FP-CIT for DAT versus SERT [corrected]....

  16. Phosphoinositide 3-kinase/Akt Pathway Mediates Fip1-like1-platelet-derived Growth Factor Receptor α-induced Cell Infiltration and Activation: Possible Molecular Mechanism for the Malignant Phenotype of Chronic Eosinophilic Leukemia

    Directory of Open Access Journals (Sweden)

    Bin Li

    2015-01-01

    Full Text Available The fip1-like1/platelet-derived growth factor receptor-α fusion gene (F/P is responsible for 14-60% cases of hypereosinophilia syndrome (HES, also known as F/P-positive chronic eosinophilic leukemia (F/P(+ CEL. The major pathogenesis of F/P(+ CEL is known to involve migration and activation of mast cells and eosinophils, leading to severe multi-organ dysfunction, but the mechanism was still unclear. Phosphoinositide 3-kinase (PI3K and serine-threonine protein kinase Akt have been reported to be targets of F/P in the F/P-promoted cell proliferation. They are extensively involved in the migration and adhesion of hematopoietic stem/progenitor cells, and also control cell invasion in some leukemias. The PI3K/Akt pathway is involved in eosinophil/neutrophil activation and infiltration; its possible role in regulating F/P induced cytotoxicity and upregulation of A4-integrin in eosinophils, and inducing eosinophil activation through controlling F/P-induced Nuclear factor-kB activity. Akt was recently shown to be stimulated by F/P, synergistically with stem cell factor, resulting in the induction of MCs migration and excessive activation. PI3K/Akt pathway is also a principal mediator of interleukin-5 (IL-5-induced signal transduction promoting eosinophil trafficking and degranulation, whereas IL-5 is a necessary cytokine for F/P-mediated CEL development. We, therefore, propose the hypothesis that the PI3K/Akt pathway might be vital downstream of F/P to induce target cell activation and tissue infiltration, resulting in the malignant phenotype seen in F/P(+ CEL.

  17. Somatostatin receptors

    DEFF Research Database (Denmark)

    Møller, Lars Neisig; Stidsen, Carsten Enggaard; Hartmann, Bolette

    2003-01-01

    therefore been acknowledged to be a third endogenous ligand at SRIF receptors. This review goes through mechanisms of signal transduction, pharmacology, and anatomical distribution of SRIF receptors. Structurally, SRIF receptors belong to the superfamily of G protein-coupled (GPC) receptors, sharing....... The generation of knock-out (KO) mice, intended as a means to define the contributions made by individual receptor subtypes, necessarily marks but an approximation. Furthermore, we must now take into account the stunning complexity of receptor co-operation indicated by the observation of receptor homo......-peptides, receptor agonists and antagonists. Relatively long half lives, as compared to those of the endogenous ligands, have been paramount from the outset. Motivated by theoretical puzzles or the shortcomings of present-day diagnostics and therapy, investigators have also aimed to produce subtype...

  18. 123I-FP-CIT brain SPECT (DaTSCAN imaging in the diagnosis of patients with movement disorders: First results

    Directory of Open Access Journals (Sweden)

    Jauković Ljiljana

    2012-01-01

    Full Text Available Background/Aim. 123I-FP-CIT brain single-photon emission computed tomography (SPECT, DaTSCAN imaging, offers a possibility to study structural and biochemical integrity of presinaptic dopaminergic neurotransmitter system. The aim of this study was to evaluate the usefulness of 123I-FP-CIT brain SPECT scintigraphy in patients with extrapyramidal diseases. Methods. Fifteen patients (8 males and 7 females, aged 26-81 years, presenting with extrapyramidal symptoms entered the study. Out of them, 7 patients were diagnosed with definite clinical form of idiopathic Parkinson’s disease (PD or clinical probable for PD clinical stage 2-4 using the Hoehn&Yahr scale (H&Y; 6 patients were with atypical parkinsonism (AP, 1 patient with essential, and 1 with psychogenic tremor. SPECT was performed 180 min after injection of 185 MBq 123IFP- CIT using a dual head Gamma camera. Sixty four one minutes’ frames were acquired using a noncircular rotation mode into a 128 × 128 image matrix. Transverse slices were reconstructed using a 0.6 order Butterworth filter. Visual interpretation was based on striatal uptake, left to right asymmetry and substructures most affected. The ratio of binding for the entire striatum, caudate and putamen to nonspecific binding in occipital cortex was calculated. SPECT findings were categorized as normal and abnormal (incipient, moderate and severe presinaptic deficit. Results. 123I-FP-CIT uptake was reduced in the striatum of 6/7 patients with PD and 5/6 patients with AP. Two patients with PD and AP showed a negative finding. The remaining 2 negative results were obtained in the patients diagnosed with essential tremor and psychogenic tremor. The mean striato-occipital ratio (SDR of the most affected side was lower in the patients with PD. Conclusion. Our first results confirm the usefulness of 123I-FPCIT brain SPECT in differential diagnosis of extrapyramidal diseases.

  19. Extrastriatal binding of [{sup 123}I]FP-CIT in the thalamus and pons: gender and age dependencies assessed in a European multicentre database of healthy controls

    Energy Technology Data Exchange (ETDEWEB)

    Koch, Walter; Unterrainer, Marcus; Xiong, Guoming; Bartenstein, Peter [University of Munich, Department of Nuclear Medicine, Munich (Germany); Diemling, Markus [Hermes Medical Solutions, Stockholm (Sweden); Varrone, Andrea [Karolinska University Hospital, Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatry Research, Stockholm (Sweden); Dickson, John C. [UCLH NHS Foundation Trust and University College, Institute of Nuclear Medicine, London (United Kingdom); Tossici-Bolt, Livia [University Hospitals Southampton NHS Trust, Department of Medical Physics, Southampton (United Kingdom); Sera, Terez [University of Szeged, Department of Nuclear Medicine and Euromedic Szeged, Szeged (Hungary); Asenbaum, Susanne [Medical University of Vienna, Department of Neurology, Vienna (Austria); Booij, Jan [University of Amsterdam, Department of Nuclear Medicine, Academic Medical Centre, Amsterdam (Netherlands); Kapucu, Ozlem L. [Gazi University, Department of Nuclear Medicine, Faculty of Medicine, Ankara (Turkey); Kluge, Andreas [ABX-CRO, Dresden (Germany); Ziebell, Morten [Rigshospitalet and University of Copenhagen, Neurobiology Research Unit, Copenhagen (Denmark); Darcourt, Jacques [University of Nice-Sophia Antipolis, Nuclear Medicine Department, Centre Antoine Lacassagne, Nice (France); Nobili, Flavio [University of Genoa, Clinical Neurology Unit, Department of Neuroscience (DINOGMI), Genoa (Italy); Pagani, Marco [CNR, Institute of Cognitive Sciences and Technologies, Rome (Italy); Karolinska Hospital, Department of Nuclear Medicine, Stockholm (Sweden); Hesse, Swen [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Leipzig University Medical Centre, Molecular Neuroimaging IFB Adiposity Diseases, Leipzig (Germany); Borght, Thierry Vander [Universite Catholique de Louvain, Nuclear Medicine Division, CHU Dinant Godinne, Yvoir (Belgium); Laere, Koen van [University Hospital and K.U. Leuven, Nuclear Medicine, Leuven (Belgium); Tatsch, Klaus [Staedtisches Klinikum Karlsruhe, Department of Nuclear Medicine, Karlsruhe (Germany); La Fougere, Christian [University of Munich, Department of Nuclear Medicine, Munich (Germany); University of Tuebingen, Department of Nuclear Medicine, Tuebingen (Germany)

    2014-10-15

    Apart from binding to the dopamine transporter (DAT), [{sup 123}I]FP-CIT shows moderate affinity for the serotonin transporter (SERT), allowing imaging of both monoamine transporters in a single imaging session in different brain areas. The aim of this study was to systematically evaluate extrastriatal binding (predominantly due to SERT) and its age and gender dependencies in a large cohort of healthy controls. SPECT data from 103 healthy controls with well-defined criteria of normality acquired at 13 different imaging centres were analysed for extrastriatal binding using volumes of interest analysis for the thalamus and the pons. Data were examined for gender and age effects as well as for potential influence of striatal DAT radiotracer binding. Thalamic binding was significantly higher than pons binding. Partial correlations showed an influence of putaminal DAT binding on measured binding in the thalamus but not on the pons. Data showed high interindividual variation in extrastriatal binding. Significant gender effects with 31 % higher binding in women than in men were observed in the thalamus, but not in the pons. An age dependency with a decline per decade (±standard error) of 8.2 ± 1.3 % for the thalamus and 6.8 ± 2.9 % for the pons was shown. The potential to evaluate extrastriatal predominant SERT binding in addition to the striatal DAT in a single imaging session was shown using a large database of [{sup 123}I]FP-CIT scans in healthy controls. For both the thalamus and the pons, an age-related decline in radiotracer binding was observed. Gender effects were demonstrated for binding in the thalamus only. As a potential clinical application, the data could be used as a reference to estimate SERT occupancy in addition to nigrostriatal integrity when using [{sup 123}I]FP-CIT for DAT imaging in patients treated with selective serotonin reuptake inhibitors. (orig.)

  20. Decreased serotonin transporters in the hypothalamus and midbrain in patients with multiple systemic atrophy: a study with [{sup 123}I]-FP-CITA

    Energy Technology Data Exchange (ETDEWEB)

    Oh, So Won; Kim, Yu Kyeong; Kim, Jon Min; Eo, Jae Seon; Lee, Won Woo; Kim, Sang Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2005-07-01

    We investigated quantification of dopaminergic transporter (DAT) and serotonergic transporter (SERT) for differentiating between multiple systemic atrophy (MSA) and idiopathic Parkinsons disease (IPD). Nfluoropropyl- 2{beta}-carbomethoxy-3{beta}-4-[{sup 123}I]-iodophenylnortropane SPECT ([123I]-FP-CIT SPECT) was performed in 6 patients with MSA, 18 with early IPD, and 6 healthy controls. Standard ROIs (region of interests) of striatal regions to evaluate DAT, and hypothalamus and midbrain for SERT were drawn on standard template images and applied to each image taken 4 hours after radiotracer injection. Striatal V3? for DAT and hypothalamic and midbrain V3? for SERT were calculated using region/reference ration based on the transient equilibrium method. Group differences were tested using ANOVA with the postHoc analysis. DAT in the putamen was significantly decreased in both patients groups with MSA and early IPD, compared with healthy control (p=0.03, p=0.05, respectively). A reduction of DAT in the caudate was significant in MSA patients (p=0.05) and showed a trend in early IPD patient. This implied least involvement of caudate in early IPD. Regarding SERT, MSA patients showed significant reduction of SERT in hypothalamus compared with controls as well as early IPD patients (p=0.05, 0.01, respectively), and also showed a tendency of decrease in SERT of the midbrain (p=0.058 vs, control). In patients with IPD, there was no significant reduction of SERT in the hypothalamus or midbrain when compared with controls. In this study, the decreased SERT in the hypothalamus and midbrain could be demonstrated in MSA patients using [{sup 123}I]-FP-CIT SPECT. We suggest that the quantification of SERT as well as DAT in [{sup 123}I]-FP-CIT SPECT is helpful to differentiate Parkinsonian disorders.

  1. CCR7 Receptor Expression in Mono-MAC-1 Cells: Modulation by Liver X Receptor α Activation and Prostaglandin E 2.

    Science.gov (United States)

    Tanné, Bérengère; Bernier, Stéphane; Dumais, Nancy

    2015-01-01

    Cell migration via chemokine receptor CCR7 expression is an essential function of the immune system. We previously showed that prostaglandin E2 (PGE2), an important immunomodulatory molecule, increases CCR7 expression and function in monocytes. Here, we explore the role of the liver X receptor α (LXRα) activation on CCR7 expression in Mono-Mac-1 (MM-1) cells in the presence of PGE2. To do this, MM-1 cells were stimulated with the LXRα synthetic agonist T0901317 in the presence or absence of PGE2. CCR7 mRNA transcription was measured using quantitative RT-PCR and protein expression was examined using flow cytometry. CCR7 function was analyzed using migration assays in response to CCL19/CCL21, which are natural ligands for CCR7. Our results show that agonist-mediated activation of LXRα in the presence of PGE2 increases CCR7 mRNA transcription and MM-1 cell migratory capacity in response to CCL19/21. In addition, our results demonstrate that engagement of the E-prostanoids 2 and 4 (EP2/EP4) receptors present on MM-1 cells is responsible for the observed increase in CCR7 mRNA expression and function during LXRα activation. Examination of monocyte migration in response to lipid derivatives such as PGE2 and oxysterols that are produced at sites of chronic inflammation would contribute to understanding the excessive monocyte migration that characterizes atherosclerosis.

  2. CCR7 Receptor Expression in Mono-MAC-1 Cells: Modulation by Liver X Receptor α Activation and Prostaglandin E2

    Directory of Open Access Journals (Sweden)

    Bérengère Tanné

    2015-01-01

    Full Text Available Cell migration via chemokine receptor CCR7 expression is an essential function of the immune system. We previously showed that prostaglandin E2 (PGE2, an important immunomodulatory molecule, increases CCR7 expression and function in monocytes. Here, we explore the role of the liver X receptor α (LXRα activation on CCR7 expression in Mono-Mac-1 (MM-1 cells in the presence of PGE2. To do this, MM-1 cells were stimulated with the LXRα synthetic agonist T0901317 in the presence or absence of PGE2. CCR7 mRNA transcription was measured using quantitative RT-PCR and protein expression was examined using flow cytometry. CCR7 function was analyzed using migration assays in response to CCL19/CCL21, which are natural ligands for CCR7. Our results show that agonist-mediated activation of LXRα in the presence of PGE2 increases CCR7 mRNA transcription and MM-1 cell migratory capacity in response to CCL19/21. In addition, our results demonstrate that engagement of the E-prostanoids 2 and 4 (EP2/EP4 receptors present on MM-1 cells is responsible for the observed increase in CCR7 mRNA expression and function during LXRα activation. Examination of monocyte migration in response to lipid derivatives such as PGE2 and oxysterols that are produced at sites of chronic inflammation would contribute to understanding the excessive monocyte migration that characterizes atherosclerosis.

  3. Comparison of the performance of {sup 18}F-FP-CIT brain PET/MR and simultaneous PET/CT: A preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Sang Don; Chun, Kyung Ah [Dept. of Nuclear Medicine, Yeungnam University Hospital, Daegu (Korea, Republic of)

    2016-09-15

    {sup 18}F-FP-CIT [{sup 1'}8F-fluorinated N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane] has been well established and used for the differential diagnosis of atypical parkinsonian disorders. Recently, combined positron emission tomography (PET)/magnetic resonance (MR) was proposed as a viable alternative to PET/computed tomography (CT). The aim of this study was to compare the performances of conventional {sup 18}F-FP-CIT brain PET/CT and simultaneous PET/MR by visual inspection and quantitative analysis. Fifteen consecutive patients clinically suspected of having Parkinson's disease were recruited for the study.{sup 18}F-FP-CIT PET was performed during PET/CT and PET/MR. PET/CT image acquisition was started 90 min after intravenous injection of {sup 18}F-FP-CIT and then PET/MR images were acquired. Dopamine transporter (DAT) density in bilateral striatal subregions was assessed visually. Quantitative analyses were performed on bilateral striatal volumes of interest (VOIs) using average standardized uptake values (SUVmeans). Intraclass correlation coefficients (ICCs) and their 95 % confidence intervals (CIs) were assessed to compare PET/CT and PET/MR data. Bland-Altman plots were drawn to perform method-comparisons. All subjects showed a preferential decrease in DAT binding in the posterior putamen (PP), with relative sparing of the ventral putamen (VP). Bilateral striatal subregional binding ratio (BR) determined PET/CT and PET/MR demonstrated close interequipment correspondence (BRright caudate - ICC, 0.944; 95 % CI, 0.835-0.981, BRleft caudate - ICC, 0.917; 95 % CI, 0.753-0.972, BRright putamen - ICC, 0.976; 95 % CI, 0.929-0.992 and BRleft putamen - ICC, 0.970; 95 % CI, 0.911-0.990, respectively), and Bland-Altman plots showed interequipment agreement between the two modalities. It is known that MR provides more information about anatomical changes associated with brain diseases and to enable the anatomical allocations of

  4. Implementation of the European multicentre database of healthy controls for [{sup 123}I]FP-CIT SPECT increases diagnostic accuracy in patients with clinically uncertain parkinsonian syndromes

    Energy Technology Data Exchange (ETDEWEB)

    Albert, Nathalie L.; Unterrainer, Marcus; Xiong, Guoming; Bartenstein, Peter; Koch, Walter [University of Munich, Department of Nuclear Medicine, Munich (Germany); Diemling, Markus [Hermes Medical Solutions, Stockholm (Sweden); Varrone, Andrea [Karolinska University Hospital, Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatry Research, Stockholm (Sweden); Dickson, John C. [UCLH NHS Foundation Trust and University College, Institute of Nuclear Medicine, London (United Kingdom); Tossici-Bolt, Livia [University Hospitals Southampton NHS Trust, Department of Medical Physics, Southampton (United Kingdom); Sera, Terez [University of Szeged, Department of Nuclear Medicine and Euromedic Szeged, Szeged (Hungary); Asenbaum, Susanne [Medical University of Vienna, Department of Neurology, Vienna (Austria); Booij, Jan [University of Amsterdam, Department of Nuclear Medicine, Academic Medical Centre, Amsterdam (Netherlands); Kapucu, L. Oezlem A. [Gazi University, Department of Nuclear Medicine, Faculty of Medicine, Ankara (Turkey); Kluge, Andreas [ABX-CRO, Dresden (Germany); Ziebell, Morten [Rigshospitalet and University of Copenhagen, Neurobiology Research Unit, Copenhagen (Denmark); Darcourt, Jacques [University of Nice-Sophia Antipolis, Nuclear Medicine Department, Centre Antoine Lacassagne, Nice (France); Nobili, Flavio [University of Genoa, Clinical Neurology Unit, Department of Neuroscience (DINOGMI), Genoa (Italy); Pagani, Marco [Institute of Cognitive Sciences and Technologies, CNR, Rome (Italy); Karolinska Hospital, Department of Nuclear medicine, Stockholm (Sweden); Sabri, Osama [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Hesse, Swen [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Leipzig University Medical Centre, Molecular Neuroimaging IFB Adiposity Diseases, Leipzig (Germany); Borght, Thierry vander [Universite Catholique de Louvain, Nuclear Medicine Division, Mont-Godinne Medical Center, Yvoir (Belgium); Laere, Koen van [University Hospital and K.U. Leuven, Nuclear Medicine, Leuven (Belgium); Tatsch, Klaus [Staedtisches Klinikum Karlsruhe, Department of Nuclear Medicine, Karlsruhe (Germany); La Fougere, Christian [University of Tuebingen, Division of Nuclear Medicine, Department of Radiology, Tuebingen (Germany)

    2016-07-15

    Even though [{sup 123}I]FP-CIT SPECT provides high accuracy in detecting nigrostriatal cell loss in neurodegenerative parkinsonian syndromes (PS), some patients with an inconclusive diagnosis remain. We investigated whether the diagnostic accuracy in patients with clinically uncertain PS with previously inconclusive findings can be improved by the use of iterative reconstruction algorithms and an improved semiquantitative evaluation which additionally implemented a correction algorithm for patient age and gamma camera dependency (EARL-BRASS; Hermes Medical Solutions, Sweden). We identified 101 patients with inconclusive findings who underwent an [{sup 123}I]FP-CIT SPECT between 2003 and 2010 as part of the diagnostic process of suspected PS at the University of Munich, and re-evaluated these scans using iterative reconstruction algorithms and the new corrected EARL-BRASS. Clinical follow-up was obtained in 62 out of the 101 patients and constituted the gold standard for the re-evaluation to assess the possible improvement in diagnostic accuracy. Clinical follow-up confirmed the diagnosis of PS in 11 of the 62 patients. In patients in whom both visual and semiquantitative analysis showed concordant findings (48 patients), a high negative predictive value (93 %), positive predictive value (100 %) and accuracy (94 %) were found, and thus a correct diagnosis was obtained in 45 of the 48 patients. Among the 14 patients with discordant findings, the additional semiquantitative analysis correctly identified all five of nine patients patients without PS by nonpathological semiquantitative findings in visually pathological or inconclusive scans. In contrast, four of the remaining five patients with decreased semiquantitative values but visually normal scans did not show a PS during follow-up. The age-corrected and camera-corrected mode of evaluation using EARL-BRASS provided a notable improvement in the diagnostic accuracy of [{sup 123}I]FP-CIT SPECT in PS patients with

  5. FP-LAPW investigation of structural, electronic, linear and nonlinear optical properties of ZnIn2Te4 defect-chalcopyrite

    OpenAIRE

    AYEB, Y.; OUAHRANI, T.; Khenata, R.; Reshak, Ali H.; RACHED, D.; Bouhemadou, A.; ARRAR, R.

    2010-01-01

    A theoretical study of structural, electronic, linear and nonlinear optical properties of ZnIn2Te4 defect-chalcopyrite is presented using the full-potential linearized augmented plane-wave (FP-LAPW) method. The exchange and correlation potential is treated by the generalized-gradient approximation (GGA). Moreover, the Engel and Vosko GGA formalism (EV-GGA) is also used to improve the band gap results. The lattice parameters (a, c) and the atomic positions (x, y and z) are optimized and found ...

  6. Potential environmental benefits of improving recycling of polyolefines – LCA of Magnetic density separation (MDS) developed in the EU FP7 funded project W2Plastic

    DEFF Research Database (Denmark)

    Olsen, Stig Irving; Bonou, Alexandra

    2012-01-01

    The core of the EU FP7 funded project W2Plastic is development of a magnetic density separation (MDS) of polyolefines in order to improve the sorting efficiency of these polymer types in different waste fractions. As part of the project a life cycle assessment is performed in order to firstly...... identify eco-design criteria for the development and secondly to document the potential environmental improvement of polyolefin recycling using the MDS technology. A preliminary study focusing solely on the carbon footprint benefits of recycling plastic waste compared to virgin production of polymers...

  7. A comparison of core degradation phenomena in the CORA, QUENCH, Phébus SFD and Phébus FP experiments

    Energy Technology Data Exchange (ETDEWEB)

    Haste, T., E-mail: tim.haste@irsn.fr [Institut de Radioprotection et de Sûreté Nucléaire, IRSN, BP 3, F-13115 St. Paul-lez-Durance Cedex (France); Steinbrück, M., E-mail: martin.steinbrueck@kit.edu [Karlsruhe Institute of Technology (KIT), Hermann-von-Helmholtz-Platz 1, D-76344 Eggenstein-Leopoldshafen (Germany); Barrachin, M., E-mail: marc.barrachin@irsn.fr [Institut de Radioprotection et de Sûreté Nucléaire, IRSN, BP 3, F-13115 St. Paul-lez-Durance Cedex (France); Luze, O. de, E-mail: olivier.de-luze@irsn.fr [Institut de Radioprotection et de Sûreté Nucléaire, IRSN, BP 3, F-13115 St. Paul-lez-Durance Cedex (France); Grosse, M., E-mail: mirco.grosse@kit.edu [Karlsruhe Institute of Technology (KIT), Hermann-von-Helmholtz-Platz 1, D-76344 Eggenstein-Leopoldshafen (Germany); Stuckert, J., E-mail: juri.stuckert@kit.edu [Karlsruhe Institute of Technology (KIT), Hermann-von-Helmholtz-Platz 1, D-76344 Eggenstein-Leopoldshafen (Germany)

    2015-03-15

    Highlights: • The results of the experiments CORA, QUENCH and Phébus SFD/FP are summarised. • All phenomena expected up to melt movement to the lower head are shown consistently. • Separate-effect tests performed at KIT and IRSN aid improve their modelling. • Data from the integral tests help independent validation of new and improved models. • The improved codes will help reduce uncertainties in safety-critical areas for core degradation. - Abstract: Over the past 20 years, integral fuel bundle experiments performed at IRSN Cadarache, France (Phébus-SFD and Phébus FP – fission heated) and at Karlsruhe Institute of Technology, Germany (CORA and QUENCH – electrically heated), accompanied by separate-effect tests, have provided a wealth of detailed information on core degradation phenomena that occur under severe accident conditions, relevant to such safety issues as in-vessel retention of the core, recovery of the core by water reflood, hydrogen generation and fission product release. These data form an important basis for development and validation of severe accident analysis codes such as ASTEC (IRSN/GRS, EC) and MELCOR (USNRC/SNL, USA) that are used to assess the safety of current and future reactor designs, so helping to reduce the uncertainty associated with such code predictions. Following the recent end of the Phébus FP project, it is appropriate now to compare the core degradation phenomena observed in these four major experimental series, indicating the main conclusions that have been drawn. This covers subjects such as early phase degradation up to loss of rod-like geometry (all the series), late phase degradation and the link between fission product release and core degradation (Phébus FP), oxidation phenomena (all the series), reflood behaviour (CORA and QUENCH), as well as particular topics such as the effects of control rod material and fuel burn-up on core degradation. It also outlines the separate-effects experiments performed to

  8. The Validation Activities of the APhoRISM EC 7FP Project, Aimed at Post Seismic Damage Mapping, Through a Combined Use of EOS and Ground Data

    Science.gov (United States)

    Devanthery, N.; Luzi, G.; Stramondo, S.; Bignami, C.; Pierdicca, N.; Wegmuller, U.; Romaniello, V.; Anniballe, R.; Piscini, A.; Albano, M.; Moro, M.; Crosetto, M.

    2016-08-01

    The estimate of damage after an earthquake using spaceborne remote sensing data is one of the main application of the change detection methodologies widely discussed in literature. APhoRISM - Advanced PRocedures for volcanIc and Seismic Monitoring is a collaborative European Commission project (FP7-SP ACE- 2013-1) addressing the development of innovative methods, using space and ground sensors to support the management and mitigation of the seismic and the volcanic risk. In this paper a novel approach aimed at damage assessment based on the use of a priori information derived by different sources in a preparedness phase is described and a preliminary validation is shown.

  9. Downregulation of protease-activated receptor-1 in human lung fibroblasts is specifically mediated by the prostaglandin E receptor EP2 through cAMP elevation and protein kinase A.

    Science.gov (United States)

    Sokolova, Elena; Hartig, Roland; Reiser, Georg

    2008-07-01

    Many cellular functions of lung fibroblasts are controlled by protease-activated receptors (PARs). In fibrotic diseases, PAR-1 plays a major role in controlling fibroproliferative and inflammatory responses. Therefore, in these diseases, regulation of PAR-1 expression plays an important role. Using the selective prostaglandin EP2 receptor agonist butaprost and cAMP-elevating agents, we show here that prostaglandin (PG)E(2), via the prostanoid receptor EP2 and subsequent cAMP elevation, downregulates mRNA and protein levels of PAR-1 in human lung fibroblasts. Under these conditions, the functional response of PAR-1 in fibroblasts is reduced. These effects are specific for PGE(2). Activation of other receptors coupled to cAMP elevation, such as beta-adrenergic and adenosine receptors, does not reproduce the effects of PGE(2). PGE(2)-mediated downregulation of PAR-1 depends mainly on protein kinase A activity, but does not depend on another cAMP effector, the exchange protein activated by cAMP. PGE(2)-induced reduction of PAR-1 level is not due to a decrease of PAR-1 mRNA stability, but rather to transcriptional regulation. The present results provide further insights into the therapeutic potential of PGE(2) to specifically control fibroblast function in fibrotic diseases.

  10. Proinflammatory cytokine and cytokine receptor gene expression kinetics following challenge with Flavobacterium psychrophilum in resistant and susceptible lines of rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Kutyrev, Ivan; Cleveland, Beth; Leeds, Timothy; Wiens, Gregory D

    2016-11-01

    Flavobacterium psychrophilum (Fp) is the causative agent of bacterial cold water disease (BCWD) which causes appreciable economic losses in rainbow trout aquaculture. We previously reported development of a genetic line, designated ARS-Fp-R that exhibits higher survival relative to a susceptible line, designated ARS-Fp-S, following either laboratory or natural on-farm challenge. The objectives of this study were to determine the temporal kinetics of gene expression between experimentally-challenged ARS-Fp-R and ARS-Fp-S fish and the correlation between gene expression and pathogen load. We developed a GeXP multiplex RT-PCR assay to simultaneously examine expression of immune-relevant genes, concentrating on tumor necrosis factor and interleukin-1 ligand/receptor systems and acute phase response genes. Spleen tissue was sampled at 6 h, 24 h, 48 h and 144 h post-challenge and pathogen load quantified by qPCR. Transcript abundance of cytokine genes tnfa1, tnfa2, tnfa3, il1b1, il1b2, il11a; acute phase response genes saa and drtp1; and putative cytokine receptors il1r1-like-b, il1r2, tnfrsf1a, tnfrsf9, tnfrsf1a-like-b increased following challenge while the transcript abundance of il1r-like-1 and tnfrsf1a-like-a decreased compared to PBS-injected line-matched control fish. Principal component analysis identified transcript levels of genes il1r-like-1 and tnfrsf1a-like-a as exhibiting differential expression between genetic lines. In summary, Fp i.p. injection challenge elicited a proinflammatory cytokine gene expression response in the spleen, with ARS-Fp-R line fish exhibiting modestly higher basal expression levels of several putative cytokine receptors. This study furthers the understanding of the immune response following Fp challenge and differences in gene expression associated with selective breeding for disease resistance.

  11. Effect of S-1 chemotherapy and FP chemotherapy on prognosis, imaging characteristics and serum marker levels after operation for gastric carcinoma

    Institute of Scientific and Technical Information of China (English)

    Qing-Hao Gong; Yi-Ting Cai; Hai-Qun Chen; Chao-Feng Zhang; Gang Dai; Song-Ming Zhu

    2016-01-01

    Objective:To analyze the effect of S-1 chemotherapy and FP chemotherapy on prognosis, imaging characteristics and serum marker levels after operation for gastric carcinoma. Methods:A total of 68 patients with gastric cancer who underwent radical surgery were included in the study and divided into observation group and control group patients (n=34) according to random number table. Control group received FP chemotherapy, observation group received S-1 chemotherapy, and then differences in serum tumor markers, illness-related factors, nutrition indexes and T cell immune function values were compared between two groups.Results: After observation group received systematic chemotherapy, serum tumor markers such as MMP-9, MMP-2, MG7-Ag, TSGF, CA72-4, CA19-9, TP and DpD as well as illness-related factors such as DKK1, MK, Leptin, Exosome and OPN were all lower than those of control group (P<0.05); nutrition and cellular immune function indexes such as TP, ALB, PA, CD4+ T and CD4+ T/ CD8+ T values were higher than those of control group and CD8+ T value was lower than that of control group (P<0.05).Conclusions:S-1 chemotherapy after operation for gastric carcinoma can inhibit the tumor activity and optimize patients’ overall condition, and it has positive clinical significance.

  12. Automatic on-line detection system design research on internal defects of metal materials based on optical fiber F-P sensing technology

    Science.gov (United States)

    Xia, Liu; Shan, Ning; Chao, Ban; Caoshan, Wang

    2016-10-01

    Metal materials have been used in aerospace and other industrial fields widely because of its excellent characteristics, so its internal defects detection is very important. Ultrasound technology is used widely in the fields of nondestructive detection because of its excellent characteristic. But the conventional detection instrument for ultrasound, which has shortcomings such as low intelligent level and long development cycles, limits its development. In this paper, the theory of ultrasound detection is analyzed. A computational method of the defects distributional position is given. The non-contact type optical fiber F-P interference cavity structure is designed and the length of origin cavity is given. The real-time on-line ultrasound detecting experiment devices for internal defects of metal materials is established based on the optical fiber F-P sensing system. The virtual instrument of automation ultrasound detection internal defects is developed based on LabVIEW software and the experimental study is carried out. The results show that this system can be used in internal defect real-time on-line locating of engineering structures effectively. This system has higher measurement precision. Relative error is 6.7%. It can be met the requirement of engineering practice. The system is characterized by simple operation, easy realization. The software has a friendly interface, good expansibility, and high intelligent level.

  13. Prostaglandin E2 regulates angiogenesis via activation of fibroblast growth factor receptor-1.

    Science.gov (United States)

    Finetti, Federica; Solito, Raffaella; Morbidelli, Lucia; Giachetti, Antonio; Ziche, Marina; Donnini, Sandra

    2008-01-25

    Prostaglandin E(2) (PGE(2)) behaves as a mitogen in epithelial tumor cells as well as in many other cell types. We investigated the actions of PGE(2) on microvascular endothelial cells (capillary venular endothelial cells) with the purpose of delineating the signaling pathway leading to the acquisition of the angiogenic phenotype and to new vessel formation. PGE(2) (100 nM) produced activation of the fibroblast growth factor receptor 1 (FGFR-1), as measured by its phosphorylation, but not of vascular endothelial growth factor receptor 2. PGE(2) stimulated the EP3 subtype receptor, as deduced by abrogation of EP3 Galpha(i) subunit activity through pertussis toxin. Consistent with this result, in human umbilical venular endothelial cells missing the EP3 receptor, PGE(2) did not phosphorylate FGFR-1. Upon binding to its receptor, PGE(2) initiated an autocrine/paracrine signaling cascade involving the intracellular activation of c-Src, activation of matrix metalloproteinase (predominantly MMP2), which in turn caused the mobilization of membrane-anchored fibroblast growth factor-2 (FGF-2). In fact, in cells unable to release FGF-2 the transfection with both FGFR-1 and EP3 did not result in FGFR-1 phosphorylation in response to PGE(2). Relevance for the FGF2-FGFR-1 system was highlighted by confocal analysis, showing receptor internalization after cell exposure to the prostanoid. ERK1/2 appeared to be the distal signal involved, its phosphorylation being sensitive to either cSrc inhibitor or FGFR-1 blocker. Finally, PGE(2) stimulated cell migration and capillary formation in aortic rings, which were severely reduced by inhibitors of signaling molecules or by receptor antagonist. In conclusion, this study provides evidence for the involvement of FGFR-1 through FGF2 in eliciting PGE(2) angiogenic responses. This signaling pattern is similar to the autocrine-paracrine mechanism which operates in endothelial cells to support neovascular growth.

  14. Prostaglandin F2α stimulates PI3K/ERK/mTOR signaling and skeletal myotube hypertrophy.

    Science.gov (United States)

    Markworth, James F; Cameron-Smith, David

    2011-03-01

    Cyclooxygenase (COX) enzymes mediate the synthesis of proinflammatory prostaglandin (PG) species from cellular arachidonic acid. COX/PGs have been implicated in skeletal muscle growth/regeneration; however, the mechanisms by which PGs influence skeletal muscle adaptation are poorly understood. The present study aimed to investigate PGF(2α) signaling and its role in skeletal myotube hypertrophy. PGF(2α) or the FP receptor agonist fluprostenol increased C2C12 myotube diameter. This effect was abolished by the FP receptor antagonist AL8810 and mammalian target of rapamycin (mTOR) inhibition. PGF(2α) stimulated time- and dose-dependent increases in the phosphorylation of extracellular receptor kinase (ERK)1/2 (Thr202/Tyr204), p70S6 kinase (p70S6K) (Thr389 and Thr421/Ser424), and eukaryotic initiation factor 4G (eIF4G) (Ser1108) without influencing Akt (Ser473). Pretreatment with the phosphoinositide 3-kinase (PI3K) inhibitor LY294002 and the ERK inhibitor PD98059 blocked F prostanoid receptor signaling responses, whereas rapamycin blocked heightened p70S6K/eIF4G phosphorylation without influencing ERK1/2 phosphorylation. These data suggest that activation of the F prostanoid receptor is coupled to C2C12 myotube growth and intracellular signaling via a PI3K/ERK/mTOR-dependent pathway.

  15. The mouse prostaglandin E receptor EP2 subtype: cloning, expression, and northern blot analysis.

    Science.gov (United States)

    Katsuyama, M; Nishigaki, N; Sugimoto, Y; Morimoto, K; Negishi, M; Narumiya, S; Ichikawa, A

    1995-09-25

    A functional cDNA clone for the mouse prostaglandin (PG) E receptor EP2 subtype was isolated from a mouse cDNA library. The mouse EP2 receptor consists of 362 amino acid residues with seven putative transmembrane domains. [3H]PGE2 bound specifically to the membrane of Chinese hamster ovary cells stably expressing the cloned receptor. This binding was displaced by unlabeled prostanoids in the order of PGE2 = PGE1 > iloprost, a stable PGI2 agonist > PGF2 alpha > PGD2. Binding was also inhibited by butaprost (an EP2 agonist) and to a lesser extent by M&B 28767 (an EP3 agonist), but not by sulprostone (an EP1 and EP3 agonist) or SC-19220 (an EP1 antagonist). PGE2 and butaprost increased the cAMP level in the Chinese hamster ovary cells in a concentration-dependent manner. Northern blot analysis revealed that EP2 mRNA is expressed most abundantly in the uterus, followed by the spleen, lung, thymus, ileum, liver, and stomach.

  16. [Comparative evaluation of speech disorders and verbal and non verbal communication within two groups of patients: patients with facial paralysis (FP) and those who had undergone hypoglosso-facial anastomosis (HFA)].

    Science.gov (United States)

    Gatignol, P; Tankere, F; Clero, D; Lobryau, Ch; Soudant, J; Lamas, G

    2003-01-01

    Speech disorders were often allotted to hypoglossal-facial anastomosis (HFA) without being clearly shown. We have compared patients with a peripheral facial paralysis at those with HFA. Retrospective study comparing verbal communication (articulation) and non-verbal within two groups of patients: patients with patient FP versus with HFA. 10 patients with idiopathic FP versus 7 patients with HFA took part in this study. The series of tests includes an evaluation of the motor possibilities, bilabial pressure measurement (for the patients with FP), speech capacities and finally an evaluation of the verbal and non-verbal communication from a scale of satisfaction. The results highlight: the presence of real speech disorders (permanent) among patients with FP and their absence among patients having profited from HFA; a real satisfaction of the HFA versus FP on the quality of life compared to daily tasks, more specifically concerning verbal and food skills. The HFA is not responsible for speech disorders, and makes undeniable improvements confirmed subsequently by the patients.

  17. Improved dopamine transporter binding activity after bone marrow mesenchymal stem cell transplantation in a rat model of Parkinson's disease: small animal positron emission tomography study with F-18 FP-CIT

    Energy Technology Data Exchange (ETDEWEB)

    Park, Bok-Nam; Lee, Kwanjae; An, Young-Sil [School of Medicine, Ajou University, Department of Nuclear Medicine and Molecular Imaging, Woncheon-dong, Yeongtong-gu, Gyeonggi-do, Suwon (Korea, Republic of); Kim, Jang-Hee; Park, So Hyun [Ajou University School of Medicine, Department of Pathology, Suwon (Korea, Republic of)

    2015-05-01

    We evaluated the effects of bone marrow-derived mesenchymal stem cells (BMSCs) in a model of Parkinson's disease (PD) using serial F-18 fluoropropylcarbomethoxyiodophenylnortropane (FP-CIT) PET. Hemiparkinsonian rats were treated with intravenously injected BMSCs, and animals without stem cell therapy were used as the controls. Serial FP-CIT PET was performed after therapy. The ratio of FP-CIT uptake in the lesion side to uptake in the normal side was measured. The changes in FP-CIT uptake were also analyzed using SPM. Behavioural and histological changes were observed using the rotational test and tyrosine hydroxylase (TH)-reactive cells. FP-CIT uptake ratio was significantly different in the BMSCs treated group (n = 28) at each time point. In contrast, there was no difference in the ratio in control rats (n = 25) at any time point. SPM analysis also revealed that dopamine transporter binding activity was enhanced in the right basal ganglia area in only the BMSC therapy group. In addition, rats that received BMSC therapy also exhibited significantly improved rotational behaviour and preservation of TH-positive neurons compared to controls. The therapeutic effect of intravenously injected BMSCs in a rat model of PD was confirmed by dopamine transporter PET imaging, rotational functional studies, and histopathological evaluation. (orig.)

  18. The discriminating nature of dopamine transporter image in parkinsonism: the competency of dopaminergic transporter imaging in differential diagnosis of parkinsonism {sup 123}I-FP-CIT SPECT study

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Bom Sahn; Jang, Sung June; Eo, Jae Seon; Park, Eun Kyung; Kim, Yu Kyeong; Kim, Jong Min; Lee, Won Woo; Kim, Sang Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2007-08-15

    The aim of this study was to evaluate the discriminating nature of {sup 123}I-FP-CIT SPECT in patients with parkinsonism. {sup 123}I-FP-CIT SPECT images acquired from the 18 normal controls; NC (60.4 {+-} 10.0 yr) and 237 patients with parkinsonism (65.9 {+-} 9.2 yr) were analyzed. From spatially normalized images, regional counts of the caudate, putamen, and occipital lobe were obtained using region of interest method. Binding potential (BP) was calculated with the ratio of specific to nonspecific binding activity at equilibrium. Additionally, the BP ratio of putamen to caudate (PCR) and asymmetric index (ASI) were measured. BPs of NC (3.37 {+-} 0.57, 3.10{+-} 0.41, 3.23 {+-} 0.48 for caudate, putamen, whole striatum, respectively) had no significant difference with those of essential tremor; ET (3.31 {+-} 0.64, 3.06 {+-} 0.61, 3.14 {+-} 0.63) and Alzheimer's disease; AD (3.33 {+-} 0.60, 3.29 {+-} 0.79, 3.31 {+-} 0.70), but were higher than those of Parkinson's disease; PD (1.92 {+-} 0.74, 1.39 {+-}0.68, 1.64 {+-} 0.68), multiple system atrophy; MSA (2.36 {+-} 1.07, 2.16 {+-} 0.91, 2.26 {+-} 0.96), and dementia with Lewy body; DLB (1.95{+-} 0.72, 1.64 {+-} 0.65, 1.79 {+-} 0.66)({rho} < 0.005). PD had statistically lower values of PCR and higher values of ASI than those of NC ({rho} < 0.005). And PD had significantly lower value of PCR, higher ASI and lower BP in the putamen and whole striatum than MSA ({rho} < 0.05). Dopamine transporter image of {sup 123}I-FP-CIT SPECT was a good value in differential diagnosis of parkinsonism.

  19. First results from SAM-FP: Fabry-Perot observations with ground-layer adaptive optics - the structure and kinematics of the core of 30 Doradus

    Science.gov (United States)

    Mendes de Oliveira, C.; Amram, P.; Quint, Bruno C.; Torres-Flores, S.; Barbá, R.; Andrade, D.

    2017-08-01

    The aim of this paper is to present the first data set obtained with SOAR Adaptive Module-Fabry-Parot (SAM-FP), a Fabry-Perot instrument mounted inside the SOAR telescope Adaptive-Optics Module. This is the only existing imaging Fabry-Perot interferometer using laser-assisted ground-layer adaptive optics. SAM-FP was used to observe the ionized gas, traced by Hα, in the centre of the 30 Doradus starburst (the Tarantula Nebula) in the Large Magellanic Cloud, with high spatial (∼0.6 arcsec, or 0.15 pc) and spectral (R ≃ 11 200) resolution. Radial velocity, velocity dispersion and monochromatic maps were derived. The region displays a mix of narrow, σ ∼ 20 km s-1 profiles and multiple broader profiles with σ ∼ 70-80 km s-1, indicating the complex nature of the nebula kinematics. A comparison with previously obtained VLT/FLAMES spectroscopy demonstrates that the data agree well in the regions of overlap, but the Fabry-Perot data are superior in spatial coverage. A preliminary analysis of the observations finds a new expanding bubble south of R136, with a projected radius of r = 5.6 pc and an expansion velocity of 29 ± 4 km s-1. In addition, the first-time detailed kinematic maps derived here for several complexes and filaments of 30 Doradus allow identification of kinematically independent structures. These data exemplify the power of the combination of a high-order Fabry-Perot with a wide-field imager (3 × 3 arcmin2 GLAO-corrected field of view) for high-resolution spatial and spectral studies. In particular, SAM-FP data cubes are highly advantageous over multifibre or long-slit data sets for nebula structure studies and to search for small-scale bubbles, given their greatly improved spatial coverage. For reference, this paper also presents two appendices with detailed descriptions of the usage of Fabry-Perot devices, including formulae and explanations for understanding Fabry-Perot observations.

  20. Effect of long-term treatment with pramipexole or levodopa on presynaptic markers assessed by longitudinal [123I]FP-CIT SPECT and histochemistry.

    Science.gov (United States)

    Depboylu, Candan; Maurer, Lukas; Matusch, Andreas; Hermanns, Guido; Windolph, Andrea; Béhé, Martin; Oertel, Wolfgang H; Höglinger, Günter U

    2013-10-01

    A previous clinical trial studied the effect of long-term treatment with levodopa (LD) or the dopamine agonist pramipexole (PPX) on disease progression in Parkinson disease using SPECT with the dopamine transporter (DAT)-radioligand [(123)I]β-CIT as surrogate marker. [(123)I]β-CIT binding declined to significantly lower levels in patients receiving LD compared to PPX. However, the interpretation of this difference as LD-induced neurotoxicity, PPX-induced neuroprotection/-regeneration, or only drug-induced regulatory changes of DAT-availability remained controversial. To address this question experimentally, we induced a subtotal lesion of the substantia nigra in mice by bilateral injection of the neurotoxin 6-hydroxydopamine. After 4 weeks, mice were treated for 20 weeks orally with LD (100mg/kg/day) or PPX (3mg/kg/day), or water (vehicle) only. The integrity of nigrostriatal projections was assessed by repeated [(123)I]FP-CIT SPECT in vivo and by immunostaining for DAT and the dopamine-synthesizing enzyme tyrosine hydroxylase (TH) after sacrifice. In sham-lesioned mice, we found that both LD and PPX treatment significantly decreased the striatal FP-CIT binding (LD: -21%; PPX: -14%) and TH-immunoreactivity (LD: -42%; PPX: -45%), but increased DAT-immunoreactivity (LD: +42%; PPX: +33%) compared to controls without dopaminergic treatment. In 6-hydroxydopamine-lesioned mice, however, neither LD nor PPX significantly influenced the stably reduced FP-CIT SPECT signal (LD: -66%; PPX: -66%; controls -66%), TH-immunoreactivity (LD: -70%; PPX: -72%; controls: -77%) and DAT-immunoreactivity (LD: -70%; PPX: -75%; controls: -75%) in the striatum or the number of TH-positive cells in the substantia nigra (LD: -88%; PPX: -88%; controls: -86%), compared to lesioned mice without dopaminergic treatment. In conclusion, chronic dopaminergic stimulation with LD or PPX induced similar adaptive presynaptic changes in healthy mice, but no discernible changes in severely lesioned mice

  1. Proteinase-activated receptor-2 stimulates prostaglandin production in keratinocytes: analysis of prostaglandin receptors on human melanocytes and effects of PGE2 and PGF2alpha on melanocyte dendricity.

    Science.gov (United States)

    Scott, Glynis; Leopardi, Sonya; Printup, Stacey; Malhi, Namrita; Seiberg, Miri; Lapoint, Randi

    2004-05-01

    Prostaglandins (PG) are key mediators of diverse functions in the skin and several reports suggest that PG mediate post-inflammatory pigmentary changes through modulation of melanocyte dendricity and melanin synthesis. The proteinase-activated receptor 2 (PAR-2) is important for skin pigmentation because activation of keratinocyte PAR-2 stimulates uptake of melanosomes through phagocytosis in a Rho-dependent manner. In this report, we show that activation of keratinocyte PAR-2 stimulates release of PGE(2) and PGF(2alpha) and that PGE(2) and PGF(2alpha) act as paracrine factors that stimulate melanocyte dendricity. We characterized the expression of the EP and FP receptors in human melanocytes and show that human melanocytes express EP1 and EP3, and the FP receptor, but not EP2 and EP4. Treatment of melanocytes with EP1 and EP3 receptor agonists resulted in increased melanocyte dendricity, indicating that both EP1 and EP3 receptor signaling contribute to PGE(2)-mediated melanocyte dendricity. Certain EP3 receptor subtypes have been shown to increase adenosine 3',5'-cyclic monophosphate (cAMP) through coupling to Gs, whereas EP1 is known to couple to Gq to activate phospholipase C with elevation in Ca(2+). The cAMP/protein kinase A system is known to modulate melanocyte dendrite formation through modulation of Rac and Rho activity. Neither PGF(2alpha) or PGE(2) elevated cAMP in human melanocytes showing that dendricity observed in response to PGE(2) and PGF(2alpha) is cAMP-independent. Our data suggest that PAR-2 mediates cutaneous pigmentation both through increased uptake of melanosomes by keratinocytes, as well as by release of PGE(2) and PGF(2alpha) that stimulate melanocyte dendricity through EP1, EP3, and FP receptors.

  2. Mechanism of Prostaglandin (PG)E2-Induced Prolactin Expression in Human T Cells: Cooperation of Two PGE2 Receptor Subtypes, E-Prostanoid (EP) 3 and EP4, Via Calcium- and Cyclic Adenosine 5'-Monophosphate-Mediated Signaling Pathways

    National Research Council Canada - National Science Library

    Gerlo, Sarah; Verdood, Peggy; Gellersen, Birgit; Hooghe-Peters, Elisabeth L; Kooijman, Ron

    2004-01-01

    ...; and Endokrinologikum Hamburg, Hamburg, Germany We previously reported that prolactin gene expression in the T-leukemic cell line Jurkat is stimulated by PGE 2 and that cAMP acts synergistically with Ca 2...

  3. Reversed-phase liquid chromatography coupled on-line to estrogen receptor bioaffinity detection based on fluorescence polarization.

    Science.gov (United States)

    Reinen, Jelle; Kool, Jeroen; Vermeulen, Nico P E

    2008-04-01

    We describe the development and validation of a high-resolution screening (HRS) platform which couples gradient reversed-phase high-performance liquid chromatography (RP-HPLC) on-line to estrogen receptor alpha (ERalpha) affinity detection using fluorescence polarization (FP). FP, which allows detection at high wavelengths, limits the occurrence of interference from the autofluorescence of test compounds in the bioassay. A fluorescein-labeled estradiol derivative (E2-F) was synthesized and a binding assay was optimized in platereader format. After subsequent optimization in flow-injection analysis (FIA) mode, the optimized parameters were translated to the on-line HRS bioassay. Proof of principle was demonstrated by separating a mixture of five compounds known to be estrogenic (17beta-estradiol, 17alpha-ethinylestradiol and the phytoestrogens coumestrol, coumarol and zearalenone), followed by post-column bioaffinity screening of the individual affinities for ERalpha. Using the HRS-based FP setup, we were able to screen affinities of off-line-generated metabolites of zearalenone for ERalpha. It is concluded that the on-line FP-based bioassay can be used to screen for the affinity of compounds without the disturbing occurrence of autofluorescence.

  4. Validación preclínica del receptor EP2 mastocitario como diana terapéutica antiasmática

    OpenAIRE

    Plaza Almolda, Judith

    2016-01-01

    El asma es una enfermedad crónica de las vías respiratorias cuyo abordaje terapéutico actual no frena su progresión, y en ocasiones no revierte la sintomatología. El análisis de mecanismos endógenos de protección puede resultar en la identificación de nuevas dianas farmacológicas efectivas. Los estudios preclínicos realizados hasta ahora en nuestro laboratorio junto con evidencia clínica y básica de otros grupos, sugirieron la hipótesis de que la activación selectiva del receptor prostanoide ...

  5. [{sup 125}I]{beta}-CIT-FE and [{sup 125}I]{beta}-CIT-FP are superior to [{sup 125}I]{beta}-CIT for dopamine transporter visualization: Autoradiographic evaluation in the human brain

    Energy Technology Data Exchange (ETDEWEB)

    Guenther, Ilonka; Hall, Haakan; Halldin, Christer; Swahn, Carl-Gunnar; Farde, Lars; Sedvall, Goeran

    1997-10-01

    The binding of the three dopamine transporter radioligands ([{sup 125}I]{beta}-CIT, [{sup 125}I]{beta}-CIT-FE, and [{sup 125}I]{beta}-CIT-FP) was studied using whole-hemisphere autoradiography on postmortem human brains. The autoradiograms revealed an intense and homogeneous labeling of the nucleus caudatus and putamen but also to varying extent to serotonergic and noradrenergic transporters of neocortex and thalamus. The order of specificity estimated (striatum over neocortex ratios) was {beta}-CIT-FP > {beta}-CIT-FE >> {beta}-CIT, suggesting that {beta}-CIT-FE and {beta}-CIT-FP should be preferred for in vivo studies of the dopamine transporter in the human brain.

  6. Quality and clinical supply considerations of Paediatric Investigation Plans for IV preparations-A case study with the FP7 CloSed project.

    Science.gov (United States)

    Hanning, Sara M; Orlu Gul, Mine; Winslade, Jackie; Baarslag, Manuel A; Neubert, Antje; Tuleu, Catherine

    2016-09-25

    A Paediatric Investigation Plan (PIP) is a development plan that aims to ensure that sufficient data are obtained through studies in paediatrics to support the generation of marketing authorisation of medicines for children. This paper highlights some practical considerations and challenges with respect to PIP submissions and paediatric clinical trials during the pharmaceutical development phase, using the FP7-funded Clonidine for Sedation of Paediatric Patients in the Intensive Care Unit (CloSed) project as a case study. Examples discussed include challenges and considerations regarding formulation development, blinding and randomisation, product labelling and shipment and clinical trial requirements versus requirements for marketing authorisation. A significant quantity of information is required for PIP submissions and it is hoped that future applicants may benefit from an insight into some critical considerations and challenges faced in the CloSed project.

  7. Recent advances on green concrete for structural purposes the contribution of the EU-FP7 project EnCoRe

    CERN Document Server

    Ferrara, Liberato; Martinelli, Enzo

    2017-01-01

    This book is mainly based on the results of the EU-funded UE-FP7 Project EnCoRe, which aimed to characterize the key physical and mechanical properties of a novel class of advanced cement-based materials incorporating recycled powders and aggregates and/or natural ingredients in order to allow partial or even total replacement of conventional constituents. More specifically, the project objectives were to predict the physical and mechanical performance of concrete with recycled aggregates; to understand the potential contribution of recycled fibers as a dispersed reinforcement in concrete matrices; and to demonstrate the feasibility and possible applications of natural fibers as a reinforcement in cementitious composites. All of these aspects are fully covered in the book. The opening chapters explain the material concept and design and discuss the experimental characterization of the physical, chemical, and mechanical properties of the recycled raw constituents, as well as of the cementitious composite incor...

  8. Study on low tempurature demulsifier test for high water- content crude fluid%原油低温破乳剂FP330评价

    Institute of Scientific and Technical Information of China (English)

    宋军; 汪丽

    2007-01-01

    以大庆采油六厂原油为研究对象,考察了不同油水组成乳化油的粘温关系;对低温破乳剂FP330的破乳效果进行了评价,结果表明:40℃时,加入破乳剂的量占乳化油的体积比为80μg·g-1时,脱水效果较好.破乳剂有助于液滴并聚,破乳速率符合一级速率方程.

  9. A robust computational solution for automated quantification of a specific binding ratio based on [123i]fp-cit SPECT images.

    Science.gov (United States)

    Oliveira, F P M; Borges Faria, D; Campos Costa, D; Tavares, J M R S

    2014-03-01

    The purpose of the current paper is to present a computational solution to accurately quantify a specific to a non-specific uptake ratio in [123I]fP-CIT single photon emission computed tomography (SPECT) images and simultaneously measure the spatial dimensions of the basal ganglia, also known as basal nuclei. A statistical analysis based on a reference dataset selected by the user is also automatically performed. The quantification of the specific to non-specific uptake ratio here is based on regions of interest defined after the registration of the image under study with a template image. The computational solution was tested on a dataset of 38 [123I]FP-CIT SPECT images: 28 images were from patients with Parkinson's disease and the remainder from normal patients, and the results of the automated quantification were compared to the ones obtained by three well-known semi-automated quantification methods. The results revealed a high correlation coefficient between the developed automated method and the three semi-automated methods used for comparison (r ≥0.975). The solution also showed good robustness against different positions of the patient, as an almost perfect agreement between the specific to non-specific uptake ratio was found (ICC=1.000). The mean processing time was around 6 seconds per study using a common notebook PC. The solution developed can be useful for clinicians to evaluate [123I]FP-CIT SPECT images due to its accuracy, robustness and speed. Also, the comparison between case studies and the follow-up of patients can be done more accurately and proficiently since the intra- and inter-observer variability of the semi-automated calculation does not exist in automated solutions. The dimensions of the basal ganglia and their automatic comparison with the values of the population selected as reference are also important for professionals in this area.

  10. Probiotic Streptococcus thermophilus FP4 and Bifidobacterium breve BR03 Supplementation Attenuates Performance and Range-of-Motion Decrements Following Muscle Damaging Exercise

    Directory of Open Access Journals (Sweden)

    Ralf Jäger

    2016-10-01

    Full Text Available Probiotics have immunomodulatory effects. However, little is known about the potential benefit of probiotics on the inflammation subsequent to strenuous exercise. In a double-blind, randomized, placebo controlled, crossover design separated by a 21-day washout, 15 healthy resistance-trained men ingested an encapsulated probiotic Streptococcus (S. thermophilus FP4 and Bifidobacterium (B. breve BR03 at 5 bn live cells (AFU concentration each, or a placebo, daily for 3 weeks prior to muscle-damaging exercise (ClinicalTrials.gov NCT02520583. Isometric strength, muscle soreness, range of motion and girth, and blood interleukin-6 (IL-6 and creatine kinase (CK concentrations were measured from pre- to 72 h post-exercise. Statistical analysis was via mixed models and magnitude-based inference to the standardized difference. Probiotic supplementation resulted in an overall decrease in circulating IL-6, which was sustained to 48 h post-exercise. In addition, probiotic supplementation likely enhanced isometric average peak torque production at 24 to 72 h into the recovery period following exercise (probiotic–placebo point effect ±90% CI: 24 h, 11% ± 7%; 48 h, 12% ± 18%; 72 h, 8% ± 8%. Probiotics also likely moderately increased resting arm angle at 24 h (2.4% ± 2.0% and 48 h (1.9% ± 1.9% following exercise, but effects on soreness and flexed arm angle and CK were unclear. These data suggest that dietary supplementation with probiotic strains S. thermophilus FP4 and B. breve BR03 attenuates performance decrements and muscle tension in the days following muscle-damaging exercise.

  11. 胶态二氧化硅SYLOID244FP固化肉桂挥发油的研究%Study on solidifying volatile oil of cinnamon with colloidal silicon dioxide SYLOID244FP

    Institute of Scientific and Technical Information of China (English)

    蒋艳荣; 张振海; 胡绍英; 贾晓斌

    2013-01-01

    目的:评价胶态二氧化硅SYLOID244FP固化肉桂挥发油的特性.方法:采用SYLOID244FP固化肉桂挥发油,以桂皮醛收率为指标,优选SYLOID244FP用量;采用差示扫描量热法和扫描电镜法对固化粉末进行物相表征;考察SY-LOID244FP对肉桂挥发油中桂皮醛体外溶出和受热稳定性的影响.结果:SYLOID244FP与肉桂挥发油最佳固化比例1∶1,肉桂挥发油被固化之后,体外溶出速率加快,受热稳定性提高.结论:SYLOID244FP吸附固化中药挥发油值得进一步研究.%Objective:To evaluate the properties of solidifying volatile oil of cinnamon with colloidal silicon dioxide SYLOID244FP.Method:Volatile oil of cinnamon was solidified by SYLOID244FP.The amount of SYLOID244FP was optimized with the cinnamaldehyde yield as criteria.Curing powder was characterized by scanning electron microscopy (SEM) and differential scanning calorimetry (DSC).The effects of SYLOID244FP on dissolution in vitro and thermal stability of cinnamaldehyde were studied.Result:The optimum solidification ratio of SYLOID244FP to volatile oil of cinnamon was 1 ∶ 1.Dissolution rate of cinnamaldehyde increasesd and its thermal stability improved after volatile oil of cinnamon was solidified.Conclusion:Solidifying herbal volatile oil with SY-LOID244FP deserves studying further.

  12. δ-Opioid receptor activation stimulates normal diet intake but conversely suppresses high-fat diet intake in mice.

    Science.gov (United States)

    Kaneko, Kentaro; Mizushige, Takafumi; Miyazaki, Yuri; Lazarus, Michael; Urade, Yoshihiro; Yoshikawa, Masaaki; Kanamoto, Ryuhei; Ohinata, Kousaku

    2014-02-15

    The central opioid system is involved in a broadly distributed neural network that regulates food intake. Here, we show that activation of central δ-opioid receptor not only stimulated normal diet intake but conversely suppressed high-fat diet intake as well. [D-Pen(2,5)]-enkephalin (DPDPE), an agonist selective for the δ-receptor, increased normal diet intake after central administration to nonfasted male mice. The orexigenic activity of DPDPE was inhibited by blockade of cyclooxygenase (COX)-2, lipocalin-type prostaglandin D synthase (L-PGDS), D-type prostanoid receptor 1 (DP(1)), and neuropeptide Y (NPY) receptor type 1 (Y1) for PGD(2) and NPY, respectively, suggesting that this was mediated by the PGD(2)-NPY system. In contrast, DPDPE decreased high-fat diet intake in mice fed a high-fat diet. DPDPE-induced suppression of high-fat diet intake was blocked by antagonists of melanocortin 4 (MC(4)) and corticotropin-releasing factor (CRF) receptors but not by knockout of the L-PGDS gene. These results suggest that central δ-opioid receptor activation suppresses high-fat diet intake via the MC-CRF system, independent of the orexigenic PGD(2) system. Furthermore, orally administered rubiscolin-6, an opioid peptide derived from spinach Rubisco, suppressed high-fat diet intake. This suppression was also blocked by centrally administered naltrindole, an antagonist for the δ-receptor, suggesting that rubiscolin-6 suppressed high-fat diet intake via activation of central δ-opioid receptor.

  13. Preparation of floating visible-light photocatalyst Fe-N-TiO2/FP-CTS and its application in degradation of dissolved diesel oil%漂浮型可见光催化剂Fe-N-TiO2/FP-CTS的制备及其对溶解性柴油的降解

    Institute of Scientific and Technical Information of China (English)

    黄嘉瑜; 王学江; 卜云洁; 张晶; 马荣荣; 赵建夫

    2015-01-01

    以漂珠为载体,用壳聚糖对漂珠进行改性,并采用溶胶凝胶法,制备了Fe-N共掺杂改性TiO2的漂浮型可见光催化剂(Fe-N-TiO2/FP-CTS),使用X射线衍射(XRD)、紫外可见分光光谱(UV-Vis)、N2吸附-脱附(BET)和扫描电子显微镜(SEM)等分析进行表征.研究结果表明,用壳聚糖改性漂珠可以增加复合光催化剂的比表面积和孔容;相较于N-掺杂TiO2/FP复合光催化剂,Fe-N共掺杂更能促进对复合光催化剂可见光的吸收;光催化4h后,Fe-N-TiO2/FP-CTS对溶解性柴油的降解率达到61.7%,明显优于Fe-N-TiO2/FP和N-TiO2/FP.当初始pH =5,柴油乳化剂浓度=120 mg/L时,复合光催化剂对溶解性柴油的光催化降解效果最佳.

  14. Treatment of APP/PS1 Double Transgenic Mice of Alzheimer ‘s Disease by Transplanting pEGFP/A2M (FP6) Transfected Neural Stem Cells into the Hippocampus%pEGFP/A2M(FP6)转染神经干细胞海马移植治疗APP/PS1双转基因AD小鼠的实验观察

    Institute of Scientific and Technical Information of China (English)

    武强; 廖光昊; 李露斯; 范文辉; 黎红华; 濮捷; 徐志鹏; 程鹤; 杨柳; 刘菲

    2013-01-01

    Objective: To observe the migration and differentiation of pEGFP/A2M (FP6) transfected neural stem cells (NSCs), the deposits of Aβ in the brain and the change of learning and memory ability of APP/PS1 double transgenic mice of Alzheimer's Disease (AD) after the NSCs were transplanted into the hippocampus. Methods: APP/PS1 transgenic AD mice were randomly divided into four groups: sham operated (SO) group, artificial cerebrospinal fluid (ACSF) group, transfected pEGFP neural stem cell (pEGFP-NSCs) group and transfected pEGFP/A2M(FP6) neural stem cell (pEGFP/A2M(FP6)-NSCs) group. The ACSF, pEGFP-NSCs or pEGFP/A2M (FP6)-NSCs were transplanted into the CA1 region of the hippocampus of the mice. The learning and memory ability of the mice were assessed with Mirror water maze test. The migration and differentiation of pEGFP/A2M(FP6) transfected NSCs and the deposits of Aβ in the brain of the mice were observed by immuno-histochemistry. Results: The latencies of pEGFP/A2M (FP6)-NSCs group and pEGFP-NSCs group were significantly shorter than that in the SO group and ASCF group (P<0.05). The latency of pEGFP/A2M(FP6)-NSCs group was shorter than that in the pEGFP-NSCs group (P<0.05). Anti-Aβ detection showed Aβ deposits in the hippocampus and cortex of pEGFP/A2M(FP6)-NSCs group and pEGFP-NSCs group were surrounded by transplanted NSCs. The amount and average size of Aβ deposits in the hippocampus and cortex of pEGFP/A2M (FP6)-NSCs group were reduced markedly, compared with the other three groups (P<0.05). The expression of Nestin was detecte after transplantation. Immunofluorescent detection indicated that majority of transplanted cells expressed GFAP while only a few cells expressed MAP-2. Conclusion: Transplantation of pEGFP/A2M (FP6)-NSCs into the hippocampal region of APP/PS1 double transgenic AD mice could reduce the Aβ deposits and promote the learning and memory ability. Partial transplanted NSCs will differentiate into neurons or astro

  15. The Growth of Malignant Keratinocytes Depends on Signaling Through the PGE2 Receptor EP11

    Directory of Open Access Journals (Sweden)

    Eric J. Thompson

    2001-01-01

    Full Text Available Recent discoveries shed light on the importance of prostaglandin (PG production in the development of skin cancer. Work by Fischer et al. demonstrates that skin tumor promotion caused by ultraviolet B radiation can be decreased by up to 89% by blocking cyclooxygenase-2 (COX-2 with the drug Celecoxib. A similar study showed that Celecoxib can decrease new tumor formation by 44% in mice that already have tumors. These studies demonstrate the importance of COX-2 and PGs in the development of squamous cell carcinoma. We have explored growth signaling in a model of skin tumor progression. Because changes in PG production have been implicated in skin carcinogenesis, we examined this pathway. We found that malignant cell lines secrete more prostaglandin E2 (PGE2 than the parental cells. We observed increased expression of COX-1 and -2. We also found that these cells express the PGE2 receptors EPi and EP4. When the cells are grown in the presence of indomethacin, the growth rate of the malignant cells is decreased. This effect can be reversed by addition of PGE2 or an EPi agonist to the medium. Thus, we have shown that skin tumor cells depend in part on PGE2 signaling through the EPi prostanoid receptor for their in vitro growth.

  16. Cloning, functional expression, and characterization of the human prostaglandin E2 receptor EP2 subtype.

    Science.gov (United States)

    Bastien, L; Sawyer, N; Grygorczyk, R; Metters, K M; Adam, M

    1994-04-22

    A cDNA clone encoding the human prostaglandin (PG) E2 receptor EP2 subtype has been isolated from a human lung cDNA library. The 1.9-kilobase pair cDNA, hEP2, encodes for a 488-amino acid protein with a predicted molecular mass of 53,115 and has the seven putative transmembrane domains characteristic of G protein-coupled receptors. The specific binding of [3H]PGE2 to COS cell membranes transfected with the hEP2 cDNA was of high affinity with an equilibrium dissociation constant (Kd) of 1 nM and the rank order of potency for prostaglandins in competition for [3H]PGE2 specific binding was PGE1 = PGE2 > iloprost > PGF2 alpha > PGD2. In competition studies using more selective prostanoid-receptor agonist and antagonists, the [3H]PGE2 specific binding was competed by MB28767, an EP3 agonist, but not by the EP1-preferring antagonists AH6809 and SC19220, or by the EP2 agonist butaprost. Electrophysiological studies of Xenopus oocytes co-injected with hEP2 and cystic fibrosis transmembrane conductance regulator (cAMP-activated Cl- channel) cDNAs detected PGE2-specific inward Cl- currents, demonstrating that the hEP2 cDNA encoded a functional receptor which produced an increase in cAMP levels. Thus, we have cloned the human EP2 receptor subtype which is functionally coupled to increase in cAMP. Northern blot analysis showed that hEP2 is expressed as a 3.8-kilobase mRNA in a number of human tissues with the highest expression levels present in the small intestine.

  17. Microglial inhibition of neuroprotection by antagonists of the EP1 prostaglandin E2 receptor

    Directory of Open Access Journals (Sweden)

    Rojas Monica A

    2009-02-01

    Full Text Available Abstract Background The EP1 receptor for the prostanoid PGE2 is a G-protein coupled receptor that has been shown to contribute to excitotoxic neuronal death. In this study we examined the influence of non-neuronal cells on neuroprotective properties of EP1 receptor antagonists (Ono 8711 and SC 51089. Methods Primary neuronal cultures systems with or without non-neuronal cells were used to examine how the neuroprotective properties of EP1 antagonists were influenced by non-neuronal cells. The influence of astrocytes or microglia were individually tested in excitotoxicity assays using a co-culture system with these cells grown on permeable transwell inserts above the neuronal-enriched cultures. The influence of microglia on PGE2 synthesis and EP1 receptor expression was examined. Results EP1 antagonists were neuroprotective in neuronal-enriched cultures (> 90% neurons but not in mixed cultures (30% neurons plus other non-neuronal cells. Co-cultures of microglia on permeable transwell inserts above neuronal-enriched cultures blocked neuroprotection by EP1 antagonists. Incubation of microglia with neuronal-enriched cultures for 48 hours prior to NMDA challenge was sufficient to block neuroprotection by EP1 antagonists. The loss of neuroprotection by EP1 antagonists was accompanied by a decrease of neuronal EP1 expression in the nucleus in cultures with microglia present. Conclusion These findings demonstrate microglial modulation of neuronal excitotoxicity through interaction with the EP1 receptor and may have important implications in vivo where microglia are associated with neuronal injury.

  18. Lipoxin Receptors

    Directory of Open Access Journals (Sweden)

    Mario Romano

    2007-01-01

    Full Text Available Lipoxins (LXs represent a class of arachidonic acid (AA metabolites that carry potent immunoregulatory and anti-inflammatory properties, LXA4 and LXB4 being the main components of this series. LXs are generated by cooperation between 5-lipoxygenase (LO and 12- or 15-LO during cell-cell interactions or by single cell types. LX epimers at carbon 15, the 15-epi-LXs, are formed by aspirin-acetylated cyclooxygenase-2 (COX-2 in cooperation with 5-LO. 15-epi-LXA4 is also termed aspirin-triggered LX (ATL. In vivo studies with stable LX and ATL analogs have established that these eicosanoids possess potent anti-inflammatory activities. A LXA4 receptor has been cloned. It belongs to the family of chemotactic receptors and clusters with formyl peptide receptors on chromosome 19. Therefore, it was initially denominated formyl peptide receptor like 1 (FPRL1. This receptor binds with high affinity and stereoselectivity LXA4 and ATL. It also recognizes a variety of peptides, synthetic, endogenously generated, or disease associated, but with lower affinity compared to LXA4. For this reason, this receptor has been renamed ALX. This review summarizes the current knowledge on ALX expression, signaling, and potential pathophysiological role. The involvement of additional recognition sites in LX bioactions is also discussed.

  19. Rostral Ventrolateral Medulla EP3 Receptor Mediates the Sympathoexcitatory and Pressor Effects of Prostaglandin E2 in Conscious Rats.

    Science.gov (United States)

    Rezq, Samar; Abdel-Rahman, Abdel A

    2016-11-01

    Whereas few studies have dealt with the central sympathoexcitatory action of the inflammatory prostanoid prostaglandin E2 (PGE2), there is no information on the expression and cardiovascular function of different PGE2 (EP) receptors in one of the major cardiovascular-regulating nuclei, the rostral ventrolateral medulla (RVLM). The current study aimed at filling this knowledge gap as well as elucidating the implicated molecular mechanisms. To achieve these goals, we showed the expression of EP2, EP3, and EP4 receptors in the RVLM and investigated their cardiovascular roles in conscious rats, ex vivo as well as in cultured PC12 cells. Intra-RVLM PGE2 significantly increased blood pressure and sympathetic dominance (spectral analysis). Studies with selective EP receptor subtype agonists and antagonists showed that these PGE2-evoked responses were only replicated by intra-RVLM activation of the EP3 receptor with its agonist sulprostone. The RVLM of PGE2-treated rats exhibited increases in c-Fos expression and extracellular signal-regulated kinase 1/2 and neuronal nitric oxide synthase phosphorylation along with oxidative stress, and PGE2 increased l-glutamate release in PC12 cells (surrogates of RVLM neurons). Abrogation of the PGE2-evoked pressor and biochemical responses only occurred following EP3 receptor blockade (N-[(5-Bromo-2-methoxyphenyl)sulfonyl]-3-[2-(2-naphthalenylmethyl)phenyl]-2-propenamide, L-798106). These findings suggest the dependence of RVLM PGE2-mediated sympathoexcitation/pressor response on local EP3 receptor signaling in conscious rats, and highlight central EP3 receptor blockade as a potential therapeutic modality for hypertension management. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  20. Efficacy of fragmin/protamine microparticles containing fibroblast growth factor-2 (F/P MPs/FGF-2) to induce collateral vessels in a rabbit model of hindlimb ischemia.

    Science.gov (United States)

    Horio, Takuya; Fujita, Masanori; Tanaka, Yoshihiro; Ishihara, Masayuki; Kishimoto, Satoko; Nakamura, Shingo; Hase, Kazuo; Maehara, Tadaaki

    2011-09-01

    The localized delivery of exogenous, angiogenic growth factors such as fibroblast growth factor (FGF)-2 has become a promising alternative treatment of peripheral artery disease (PAD) and critical limb ischemia (CLI). The present study describes the efficacy of fragmin/protamine microparticles containing FGF-2 (F/P-MPs/FGF-2) to promote vessel growth in a rabbit model of hindlimb ischemia. A total of 24 rabbits were used to construct a model of hindlimb ischemia by resection of the left femoral artery. The rabbits were randomly divided into four groups 10 days after surgery (day 0); group A: control (non-treated; 1 mL of phosphate-buffered saline [PBS]); group B: FGF-2 (100 μg FGF-2 in 1 mL PBS)-treated; group C: F/P-MPs (12 mg dried F/P MPs in 1 mL PBS)-treated; and group D; F/P MPs/FGF-2 (100 μg FGF-2 and 12 mg dried F/P MPs in 1 mL PBS)-treated (n = 6 each). The drugs were administered intramuscularly to each group. Blood flow and blood pressure were measured in each group on days 0, 14, and 28. Angiography was performed to assess arteriogenesis on day 28. The number of capillaries on day 28 was determined by direct counting CD31(-) and α-smooth muscle antibody (α-SMA)-positive vessels. Neither death nor wound infection was observed throughout the experiment. The F/P MPs/FGF-2-treated group showed marked improvement in the blood flow ratio, blood pressure ratio, and capillary number in comparison to the control group, FGF-2-treated group, and F/P MPs-treated group. The F/P MPs-treated group showed intermediate improvement in blood flow ratio and capillary number in comparison to the control group and FGF-2-treated group. The F/P MPs/FGF-2-treated group strongly induced functional collateral vessels in the rabbit model of hindlimb ischemia, indicating a possible therapy for PAD. Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

  1. Control of the Cavity Length Consistency of Miniaturization Optical Fiber F-P Sensor%微型化光纤法布里-珀罗传感器腔长一致性的控制研究

    Institute of Scientific and Technical Information of China (English)

    童杏林; 文昌山; 朱小龙; 王夏; 纪涛; 冷卓燕

    2012-01-01

    A kind of optical fiber F-P sensor was studied for the control of the cavity length consistency. The cavity length was controlled by three-dimension frames. On the basis of the F-P cavity principle, the F-P cavity was under real-time detection by spectrum analyzer and then was adjusted. The F-P cavity was composed of hollow glass tube and optical fiber with the method of thermal fusion. The key parts of the processed F-P cavity were examined using optical microscope, and the fusion points were examined on their robustness. The results show that the F-P cavity length is better controlled and the consistency is good. The fusion areas are little out of shape and it has few influences on the F-P cavity's performance.%研究了光纤法布里-珀罗腔传感器的腔长一致性的控制技术,通过三维调整架组成微调装置来控制全光纤法布里-珀罗腔的腔长;结合法布里-珀罗腔的工作原理,利用光谱分析仪实时检测加工过程中法布里-珀罗腔的腔长并用装置予以修正;以热熔接的方法将毛细玻璃管与光纤加工成法布里-珀罗腔;利用超景深光学显微系统检查加工的法布里-珀罗腔的关键部位的结构,并对熔接点的牢固性进行了检测.实验结果和数据分析显示:法布里-珀罗腔的腔长得到了较好的控制及一致性,熔接部位的变形和对法布里-珀罗腔的性能的影响也很小.该工艺可用于制备全光纤法布里-珀罗腔传感器.

  2. Comparison of two neural network classifiers in the differential diagnosis of essential tremor and Parkinson's disease by {sup 123}I-FP-CIT brain SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Palumbo, Barbara [University of Perugia, Nuclear Medicine Section, Department of Surgical, Radiological and Odontostomatological Sciences, Ospedale S. Maria della Misericordia, Perugia (Italy); Fravolini, Mario Luca [University of Perugia, Department of Electronic and Information Engineering, Perugia (Italy); Nuvoli, Susanna; Spanu, Angela; Madeddu, Giuseppe [University of Sassari, Department of Nuclear Medicine, Sassari (Italy); Paulus, Kai Stephan [University of Sassari, Department of Neurology, Sassari (Italy); Schillaci, Orazio [University Tor Vergata, Department of Biopathology and Diagnostic Imaging, Rome (Italy); IRCSS Neuromed, Pozzilli (Italy)

    2010-11-15

    To contribute to the differentiation of Parkinson's disease (PD) and essential tremor (ET), we compared two different artificial neural network classifiers using {sup 123}I-FP-CIT SPECT data, a probabilistic neural network (PNN) and a classification tree (ClT). {sup 123}I-FP-CIT brain SPECT with semiquantitative analysis was performed in 216 patients: 89 with ET, 64 with PD with a Hoehn and Yahr (H and Y) score of {<=}2 (early PD), and 63 with PD with a H and Y score of {>=}2.5 (advanced PD). For each of the 1,000 experiments carried out, 108 patients were randomly selected as the PNN training set, while the remaining 108 validated the trained PNN, and the percentage of the validation data correctly classified in the three groups of patients was computed. The expected performance of an ''average performance PNN'' was evaluated. In analogy, for ClT 1,000 classification trees with similar structures were generated. For PNN, the probability of correct classification in patients with early PD was 81.9{+-}8.1% (mean{+-}SD), in patients with advanced PD 78.9{+-}8.1%, and in ET patients 96.6{+-}2.6%. For ClT, the first decision rule gave a mean value for the putamen of 5.99, which resulted in a probability of correct classification of 93.5{+-}3.4%. This means that patients with putamen values >5.99 were classified as having ET, while patients with putamen values <5.99 were classified as having PD. Furthermore, if the caudate nucleus value was higher than 6.97 patients were classified as having early PD (probability 69.8{+-}5.3%), and if the value was <6.97 patients were classified as having advanced PD (probability 88.1%{+-}8.8%). These results confirm that PNN achieved valid classification results. Furthermore, ClT provided reliable cut-off values able to differentiate ET and PD of different severities. (orig.)

  3. Adenylyl cyclase type 6 overexpression selectively enhances beta-adrenergic and prostacyclin receptor-mediated inhibition of cardiac fibroblast function because of colocalization in lipid rafts.

    Science.gov (United States)

    Liu, Xiaoqiu; Thangavel, Muthusamy; Sun, Shu Qiang; Kaminsky, Joseph; Mahautmr, Penden; Stitham, Jeremiah; Hwa, John; Ostrom, Rennolds S

    2008-06-01

    Cardiac fibroblasts produce and degrade extracellular matrix and are critical in regulating cardiac remodeling and hypertrophy. Fibroblasts are activated by factors such as transforming growth factor beta and inhibited by agents that elevate 3',5'-cyclic adenosine monophosphate (cAMP) levels. cAMP signal generation and response is known to be compartmentalized in many cell types in part through the colocalization of receptors and specific adenylyl cyclase isoforms in lipid rafts and caveolae. The present study sought to define the localization of key G protein-coupled receptors with adenylyl cyclase type 6 (AC6) in lipid rafts of rat cardiac fibroblasts and to determine if this colocalization was functionally relevant. We found that cardiac fibroblasts produce cAMP in response to agonists for beta-adrenergic (isoproterenol), prostaglandin EP2 (butaprost), adenosine (adenosine-5'-N-ethylcarboxamide, NECA), and prostacyclin (beraprost) receptors. Overexpression of AC6 increased cAMP production stimulated by isoproterenol and beraprost but not by butaprost or NECA. A key function of fibroblasts is the production of collagen. Isoproterenol- and beraprostmediated inhibition of collagen synthesis was also enhanced by AC6 overexpression, while inhibition by butaprost and NECA were unaltered. Lipid raft fractions from cardiac fibroblasts contain the preponderance of beta-adrenergic receptors and AC6 but exclude EP2 receptors. While we could not determine the localization of native prostacyclin receptors, we were able to determine that epitope-tagged prostanoid IP receptors (IPR) expressed in COS7 cells did localize, in part, in lipid raft fractions. These findings indicate that IP receptors are expressed in lipid rafts and can activate raft-localized AC isoforms. AC6 is completely compartmentized in lipid raft domains where it is activated solely by coresident G protein-coupled receptors to regulate cardiac fibroblast function.

  4. Up-regulation of EP2 and EP3 receptors in human tolerogenic dendritic cells boosts the immunosuppressive activity of PGE2.

    Science.gov (United States)

    Flórez-Grau, Georgina; Cabezón, Raquel; Borgman, Kyra J E; España, Carolina; Lozano, Juan Jose; Garcia-Parajo, Maria F; Benítez-Ribas, Daniel

    2017-09-01

    Dendritic cells (DCs) are APCs essential in regulating the immune response. PGE2, produced during inflammation, has a pivotal role in the maturation of DCs and, therefore, is vital for the immune response. The large variety of biologic functions governed by PGE2 is mediated by its signaling through 4 distinct E-type prostanoid (EP) receptors. Immunogenic DCs express EP2 and EP4, which mediate the PGE2 signaling. However, the expression and function of EP receptors in human tolerogenic DCs (tol-DCs), which present an inhibitory phenotype, have not yet, to our knowledge, been assessed. To clarify the role of EP receptors in tol-DCs, we examined the expression of different EP receptors and their effect using selective agonists in human cells. We find that EP2 and EP3 expression are up-regulated in in vitro-generated tol-DCs compared with mature DCs (mDCs). Activation of EP2-EP4 has a direct effect on the surface expression of costimulatory molecules and maturation receptors, such as CD80, CD83, and CD86 or MHCII and CCR7 in tol-DCs, the latter being exclusively modulated by PGE2-EP4 signaling. Importantly, we find that EP2 and EP3 receptors are involved in tolerance induction through IL-10 production by tol-DCs. These results are in sharp contrast with the inflammatory role of EP4 Moreover, we show that DCs generated in the presence of agonists for EP receptors, induce naive T cell differentiation toward polarized Th1/Th17 cells. Given the differential effects of EP receptors, our results suggest that EP receptor agonist/antagonists might become relevant novel drug templates to modulate immune response. © Society for Leukocyte Biology.

  5. Broadband finite-pulse radio-frequency-driven recoupling (fp-RFDR) with (XY8)4(1) super-cycling for homo-nuclear correlations in very high magnetic fields at fast and ultra-fast MAS frequencies.

    Science.gov (United States)

    Shen, Ming; Hu, Bingwen; Lafon, Oliver; Trébosc, Julien; Chen, Qun; Amoureux, Jean-Paul

    2012-10-01

    We demonstrate that inter-residue (13)C-(13)C proximities (of about 380 pm) in uniformly (13)C-labeled proteins can be probed by applying robust first-order recoupling during several milliseconds in single-quantum single-quantum dipolar homo-nuclear correlation (SQ-SQ D-HOMCOR) 2D experiments. We show that the intensity of medium-range homo-nuclear correlations in these experiments is enhanced using broadband first-order finite-pulse radio-frequency-driven recoupling (fp-RFDR) NMR sequence with a nested (XY8)4(1) super-cycling. The robustness and the efficiency of the fp-RFDR-(XY8)4(1) method is demonstrated at high magnetic field (21.1T) and high Magic-Angle Spinning (MAS) speeds (up to 60 kHz). The introduced super-cycling, formed by combining phase inversion and a global four-quantum phase cycle, improves the robustness of fp-RFDR to (i) chemical shift anisotropy (CSA), (ii) spread in isotropic chemical shifts, (iii) rf-inhomogeneity and (iv) hetero-nuclear dipolar couplings for long recoupling times. We show that fp-RFDR-(XY8)4(1) is efficient sans (1)H decoupling, which is beneficial for temperature-sensitive biomolecules. The efficiency and the robustness of fp-RFDR-(XY8)4(1) is investigated by spin dynamics numerical simulations as well as solid-state NMR experiments on [U-(13)C]-L-histidine·HCl, a tetra-peptide (Fmoc-[U-(13)C,(15)N]-Val-[U-(13)C,(15)N]-Ala-[U-(13)C,(15)N]-Phe-Gly-t-Boc) and Al(PO(3))(3).

  6. Role of the prostaglandins in labour and prostaglandin receptor inhibitors in the prevention of preterm labour.

    Science.gov (United States)

    Olson, David M; Ammann, Christina

    2007-01-01

    Parturition is composed of five separate but integrated physiological events: fetal membrane rupture, cervical dilatation, myometrial contractility, placental separation, and uterine involution. Prostaglandins (PGs) have central roles in each of these events, but the most studied is myometrial contraction. Elevated uterine PGs or the enhanced sensitivity of the myometrium to PGs leads to contractions and labour. The primary regulator of PG synthesis is the mRNA expression of PG H Synthase (PGHS-2 or COX-2). Given the central role of PGs in labour, this enzyme becomes an obvious therapeutic target for the prevention of preterm labour, the major cause of perinatal mortality and morbidity. Unfortunately, even though the non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit PGHS, are usually successful in suppressing preterm labour or prolonging pregnancy in animal and human studies, the NSAIDS have had adverse effects on fetal physiology and development. Therefore, other means to suppress PG synthesis or action to arrest preterm labour need to be investigated. The PGF2alpha receptor, FP, may prove to be a reasonable target for tocolysis. FP mRNA increases in the mouse uterus at preterm birth, whereas PGF2alpha concentrations do not increase, suggesting elevated uterine sensitivity to contractile agonists is one mechanism for preterm labour initiation. New data shows that administration of a specific FP antagonist, Theratechnologies (THG) 113.31, delays preterm birth in mice and sheep with no observable maternal or fetal side effects. Hence antagonizing PG action offers new hope for delaying preterm birth.

  7. Novel mechanisms and signaling pathways of esophageal ulcer healing: the role of prostaglandin EP2 receptors, cAMP, and pCREB.

    Science.gov (United States)

    Ahluwalia, Amrita; Baatar, Dolgor; Jones, Michael K; Tarnawski, Andrzej S

    2014-09-15

    Clinical studies indicate that prostaglandins of E class (PGEs) may promote healing of tissue injury e.g., gastroduodenal and dermal ulcers. However, the precise roles of PGEs, their E-prostanoid (EP) receptors, signaling pathways including cAMP and cAMP response element-binding protein (CREB), and their relation to VEGF and angiogenesis in the tissue injury healing process remain unknown, forming the rationale for this study. Using an esophageal ulcer model in rats, we demonstrated that esophageal mucosa expresses predominantly EP2 receptors and that esophageal ulceration triggers an increase in expression of the EP2 receptor, activation of CREB (the downstream target of the cAMP signaling), and enhanced VEGF gene expression. Treatment of rats with misoprostol, a PGE1 analog capable of activating EP receptors, enhanced phosphorylation of CREB, stimulated VEGF expression and angiogenesis, and accelerated esophageal ulcer healing. In cultured human esophageal epithelial (HET-1A) cells, misoprostol increased intracellular cAMP levels (by 163-fold), induced phosphorylation of CREB, and stimulated VEGF expression. A cAMP analog (Sp-cAMP) mimicked, whereas an inhibitor of cAMP-dependent protein kinase A (Rp-cAMP) blocked, these effects of misoprostol. These results indicate that the EP2/cAMP/protein kinase A pathway mediates the stimulatory effect of PGEs on angiogenesis essential for tissue injury healing via the induction of CREB activity and VEGF expression.

  8. Inventory of uncertainties associated with the process of tsunami damage assessment on buildings (SCHEMA FP6 EC co-funded project

    Directory of Open Access Journals (Sweden)

    A. Gardi

    2011-03-01

    Full Text Available Within the framework of the SCHEMA FP6 EC co-funded project (http://www.schemaproject.org, we have identified the sources of errors/uncertainties that can be introduced at several steps of the damage assessment process, from post-disaster field measures up to hazard and damages maps production. Errors, for instance, are introduced when collecting post-disaster observations owing to different types of instruments/methods, water marks considered, tide correction, etc.: in extreme cases, differences of meters can be found between water heights data published by different teams for the same locations. Much uncertainty comes from difficulties in identifying and characterizing the potential tsunami sources and from numerical modelling. Moreover, the resolution of the employed Digital Terrain Models can noticeably affect the predicted inundation extent. We have also verified that the consistency of the computations on the long term varies sensitively depending on the code, raising the problem of results reliability for emergency management in dangerous coasts exposed to repeated waves. In addition, damage assessment is performed using damage functions linking the mean damage level on buildings with the maximum water elevation measured in the field without considering other tsunami parameters such as stream velocity. Finally, we examined uncertainties introduced in hazard and vulnerability mapping due to cartographic processing.

  9. Silicon Light: a European FP7 project aiming at high efficiency thin film silicon solar cells on foil. Monolithic series interconnection of flexible thin-film PV devices

    Energy Technology Data Exchange (ETDEWEB)

    Soppe, W. [ECN Solar Energy, P.O. Box 1, 1755 ZG Petten (Netherlands); Haug, F.J. [Ecole Polytechnique Federale de Lausanne EPFL, Photovoltaics and Thin Film Electronics Laboratory, Rue A.-L. Breguet 2, 2000 Neuchatel (Switzerland); Couty, P. [VHFTechnologies SA, Rue Edouard-Verdan 2, CH-1400 Yverdon-les-Bains (Switzerland); Duchamp, M. [Technical University of Denmark, Center for Electron Nanoscopy, DK-2800 Kongens Lyngby (Denmark); Schipper, W. [Nanoptics GmbH, Innungstr.5, 21244 Buchholz (Germany); Krc, J. [University of Ljubljana, Faculty of Electrical Engineering, Trzaska 25, SI-1000 Ljubljana (Slovenia); Sanchez, G. [Universidad Politecnica de Valencia, I.U.I. Centro de Tecnologia Nanofotonica, 46022 Valencia (Spain); Leitner, K. [Umicore Thin Film Products AG, Balzers (Liechtenstein); Wang, Q. [Shanghai Jiaotong University, Research Institute of Micro/Nanometer Science and Technology, 800 Dongchuan Road, Min Hang, 200240 Shanghai (China)

    2011-09-15

    Silicon-Light is a European FP7 project, which started January 1st, 2010 and aims at development of low cost, high-efficiency thin film silicon solar cells on foil. Three main routes are explored to achieve these goals: (a) advanced light trapping by implementing nanotexturization through UV Nano Imprinting Lithography (UV-NIL); (b) growth of crack-free silicon absorber layers on highly textured substrates; (c) development of new TCOs which should combine the best properties of presently available materials like ITO and AZO. The paper presents the midterm status of the project results, showing model calculations of ideal nanotextures for light trapping in thin film silicon solar cells; the fabrication of masters and the replication and roll-to-roll fabrication of these nanotextures. Further, results on ITO variants with improved work function are presented. Finally, the status of cell fabrication on foils with nanotexture is shown. Microcrystalline and amorphous silicon single junction cells with stable efficiencies with more than 8% have been made, paving the way towards a-Si/{mu}c-Si tandem cells with more than 11% efficiency.

  10. Ecotoxicity testing and environmental risk assessment of iron nanomaterials for sub-surface remediation – Recommendations from the FP7 project NanoRem

    DEFF Research Database (Denmark)

    Hjorth, Rune; Coutris, Claire; Nguyen, Nhung

    2017-01-01

    Nanoremediation with iron (Fe) nanomaterials opens new doors for treating contaminated soil and groundwater, but is also accompanied by new potential risks as large quantities of engineered nanomaterials are introduced into the environment. In this study, we have assessed the ecotoxicity of four ......, aggregation and sedimentation behavior in aqueous media. This paper provides a number of recommendations concerning future testing of Fe nanomaterials and discusses environmental risk assessment considerations related to these.......Nanoremediation with iron (Fe) nanomaterials opens new doors for treating contaminated soil and groundwater, but is also accompanied by new potential risks as large quantities of engineered nanomaterials are introduced into the environment. In this study, we have assessed the ecotoxicity of four...... engineered Fe nanomaterials, specifically, Nano-Goethite, Trap-Ox Fe-zeolites, Carbo-Iron® and FerMEG12, developed within the European FP7 project NanoRem for sub-surface remediation towards a test battery consisting of eight ecotoxicity tests on bacteria (V. fisheri, E. coli), algae (P. subcapitata...

  11. Passively Q-switched laser with single longitudinal mode based on the frequency selection of grating and F-P etalon in twisted-mode folded cavity

    Institute of Scientific and Technical Information of China (English)

    Bao'an Song; Weijiang Zhao; Deming Ren; Yanchen Qu; Heyong Zhang; Liming Qian; Xiaoyong Hu

    2009-01-01

    A passively Q-switched side-pumped laser with folded resonator is specially constructed for singlelongitudinal-mode smooth pulse output.Nd:YAG is chosen as the laser active medium and Cr4+:YAG as the saturable absorber medium.Additionally,the method of frequency selection by grating with 1200 line/mm and Fabry-Perot(F-P)etalon is used in the twisted-mode cavity.The single-frequency smooth pulses are produced with 10-Hz repetition rate,20-ns pulse width,and 1.064-μm wavelength.The probability of single-frequency laser output measured is over 99% by using the methods of Fourier analysis and F-P etalon multiple-beam interferometry at the threshold voltage.The measured near-field and far-field angles of divergence axe 1.442 and 1.315 mrad,respectively.The values of M2 are 1.32 and 1.31 separately with the knife-edge method.Single pulse at 1.064 μm with the energy of 8.8 mJ is achieved in TEM00 mode.

  12. Progression of dopaminergic degeneration in dementia with Lewy bodies and Parkinson's disease with and without dementia assessed using {sup 123}I-FP-CIT SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Colloby, Sean J.; McKeith, Ian G.; O' Brien, John T. [Newcastle University, Institute for Ageing and Health, Wolfson Research Centre, Newcastle General Hospital, Newcastle upon Tyne (United Kingdom); Williams, E. David [Sunderland Royal Hospital, Regional Medical Physics Department, Sunderland (United Kingdom); Burn, David J. [Newcastle General Hospital, Department of Neurology, Newcastle upon Tyne (United Kingdom); Lloyd, Jim J. [Royal Victoria Infirmary, Regional Medical Physics Department, Newcastle upon Tyne (United Kingdom)

    2005-10-01

    The objective of this study was to investigate the rate of progression of nigrostriatal dopaminergic loss in subjects with dementia with Lewy bodies (DLB), Parkinson's disease (PD) and PD with dementia (PDD) using serial {sup 123}I-FP-CIT SPECT imaging. We hypothesised that striatal rates of decline in patients would be greater than in controls, and that DLB and PDD would show similar rates, reflecting the similarity in neurobiological mechanisms of dopaminergic loss between the two disorders. We studied 20 patients with DLB, 20 with PD, 15 with PDD and 22 healthy age-matched controls. Semi-automated region of interest (ROI) analysis was performed on both baseline and repeat scans for each subject and mean striatal uptake ratios (caudate, anterior and posterior putamen) were calculated. Rates of decline in striatal binding between groups were assessed using ANCOVA. Significant differences between patients and controls were observed in caudate (DLB, PD, PDD, p{<=}0.01), anterior putamen (DLB, PDD, p{<=}0.05; PD, p=0.07) and posterior putamen (DLB, PD, PDD, p<0.006). Rates of decline were similar between DLB, PD and PDD. (orig.)

  13. The Italian forest sites of FunDivEUROPE: a new FP7 project on the functional significance of forest biodiversity in Europe

    Directory of Open Access Journals (Sweden)

    Bussotti F

    2012-12-01

    Full Text Available The Italian forest sites of FunDivEUROPE: a new FP7 project on the functional significance of forest biodiversity in Europe. FunDivEUROPE is a new project aiming at a deeper understanding of the role of forest diversity on ecosystem functions and service provisioning for society. This project combines three scientific platforms: experimental, exploratory and inventory. The exploratory platform is based on the observation of a broad range of properties, traits and ecological processes on a network of ca. 240 natural forest sites representing a gradient of tree species diversity in six focal regions of Europe (Spain, Italy, Germany, Poland, Finland and Romania. The Italian sites are located on the hills of central and Southern Tuscany and represent the category “thermophilous deciduous forest”. Almost one year of fieldwork was needed to select and characterize 36 plots measuring 30 x 30 m. Selection was based on criteria concerning tree mixtures and richness, structural parameters and main environmental variables. The main features of these sites are synthetically presented in this paper together with a short description of the project structure and scope. The aim is also to enhance dissemination of the potential implications for a sustainable forest management in Italy.

  14. NBS for Drought risks reduction in the Algarve (Portugal): selected achievements from PT FCT ProWaterMan and from EU FP7 MARSOL projects

    Science.gov (United States)

    Lobo-Ferreira, João-Paulo

    2017-04-01

    Southern Europe and the Mediterranean region are facing the challenge of managing its water resources under conditions of increasing scarcity and/or floods, besides concerns about water quality. Innovative water management strategies with nature-based solutions, such as the storage of excess water during floods, in Managed Aquifer Recharge (MAR) schemes can greatly decrease the risk of floods while it increases water availability for future use, eventually in drought periods. The Algarve region is the southern most region of Portugal mainland. It has an area of 4,997 km2 and about 451 thousand permanent inhabitants. Selected achievements of two research projects (Portugal FCT sponsored ProWaterMan project and EU FP7 sponsored MARSOL project), will be addressed regarding the Campina de Faro and Querença-Silves aquifers in the Algarve. In Faro, the idea of harvesting rainwater from the greenhouse rooftops and using this water to recharge aquifers is not new. However, using this NbS as a climate mitigation and adaptation tool with the overall impact and wide range of benefits is a step forward in innovative methodologies. This NbS can have particular positive impacts in Mediterranean conditions with (new) precipitation patterns, more intense but less frequent. The potential greenhouses surface area of about 2.74 km2 can be used by connecting these infrastructures to several large wells aiming to infiltrate an amount of 1.63 hm3/year of harvested water. There is a strong support from the Portuguese Water Agency (Agência Portuguesa do Ambiente, I.P., Algarve branch), the Water Supplier and Wastewater (Águas do Algarve, S.A.), and the local farmers and land owners which have frequent flood and/or drought problems, represented by HUBEL (a SME that produces most greenhouses for Faro area) in this project. During EU 7FP INO-DEMO MARSOL project, a survey about protection and preservation of groundwater was conducted with a sample of Portuguese farmers of the Algarve

  15. FP-LAPW calculations of the elastic, electronic and thermoelectric properties of the filled skutterudite CeRu{sub 4}Sb{sub 12}

    Energy Technology Data Exchange (ETDEWEB)

    Shankar, A., E-mail: amitshan2009@gmail.com [Condensed Matter Theory Group, Department of Physics, Mizoram University, 796004 (India); Rai, D.P. [Department of Physics, Pachhunga University College, Aizawl 796001 (India); Chettri, Sandeep [Condensed Matter Theory Group, Department of Physics, Mizoram University, 796004 (India); Khenata, R. [Laboratoire de Physique Quantique et de Modélisation Mathématique (LPQ3M), Département de Technologie, Université de Mascara, 29000 (Algeria); Thapa, R.K. [Condensed Matter Theory Group, Department of Physics, Mizoram University, 796004 (India)

    2016-08-15

    We have investigated the electronic structure, elastic and thermoelectric properties of the filled skutterudite CeRu{sub 4}Sb{sub 12} using the density functional theory (DFT). The full potential linearized augmented plane wave (FP-LAPW) method within a framework of the generalized gradient approximation (GGA) approach is used to perform the calculations presented here. The electronic structure calculation suggests an indirect band gap semiconducting nature of the material with energy band gap of 0.08 eV. The analysis of the elastic constants at relaxed positions reveals the ductile nature of the sample material with covalent contribution in the inter-atomic bonding. The narrow band gap semiconducting nature with high value of Seebeck coefficient suggests the possibility of the thermoelectric application of the material. The analysis of the thermal transport properties confirms the result obtained from the energy band structure of the material with high thermopower and dimensionless figure of merit 0.19 at room temperature.

  16. Multiple short-lived stellar prominences on O stars: The O6.5I(n)fp star lambda Cephei

    CERN Document Server

    Sudnik, N P

    2016-01-01

    Most O and many B stars show unexplained cyclical variability in their spectral lines, i.e. modulation on the rotational timescale, but not strictly periodic. The variability occurs in the so-called discrete absorption components (DACs) that accelerate through the UV-wind line profiles and also in many optical lines. For such OB stars no dipolar magnetic fields have been detected with upper limits of ~300G. We investigate whether multiple magnetic loops on the surface rather than non-radial pulsations or a dipolar magnetic field can explain the observed cyclical UV and optical spectral line variability. We present time-resolved, high-resolution optical spectroscopy of the O6.5I(n)fp star lambda Cep. We apply a simplified phenomenological model in which multiple spherical blobs attached to the surface represent magnetic-loop structures, which we call stellar prominences, by analogy with solar prominences. We compare the calculated line profiles as a function of rotational phase, adopting a rotation period of 4...

  17. Opioid Receptors.

    Science.gov (United States)

    Stein, Christoph

    2016-01-01

    Opioids are the oldest and most potent drugs for the treatment of severe pain. Their clinical application is undisputed in acute (e.g., postoperative) and cancer pain, but their long-term use in chronic pain has met increasing scrutiny. This article reviews mechanisms underlying opioid analgesia and other opioid actions. It discusses the structure, function, and plasticity of opioid receptors; the central and peripheral sites of analgesic actions and side effects; endogenous and exogenous opioid receptor ligands; and conventional and novel opioid compounds. Challenging clinical situations, such as the tension between chronic pain and addiction, are also illustrated.

  18. Palmitoylation of Gαq determines its association with the thromboxane receptor in hypoxic pulmonary hypertension.

    Science.gov (United States)

    Sikarwar, Anuraq S; Hinton, Martha; Santhosh, K Thomas; Chelikani, Prashen; Dakshinamurti, Shyamala

    2014-01-01

    Pulmonary arterial vasoconstriction is a hallmark of persistent pulmonary hypertension of the newborn (PPHN). We reported increased calcium responses to thromboxane and selectively increased thromboxane prostanoid (TP) association with Gαq in hypoxic pulmonary artery. Palmitoylation of Gαq is important for efficient receptor-Gαq-phospholipase-C interactions. TPα receptor is not itself amenable to palmitoylation. We studied the role of Gαq palmitoylation in constriction of hypoxic pulmonary artery using pharmacological palmitoylation inhibition, the effects of hypoxia on palmitoylation, and the effects of site-specific cysteine substitution mutations of Gαq on Gαq membrane targeting, TPα association, and calcium dose-response curve to a TP agonist. PPHN pulmonary artery and HEK293T cells expressing TPα were exposed to irreversible palmitoylation inhibitor 2-bromopalmitate before challenge with TP agonist U46619. Palmitate uptake was studied in hypoxic and normoxic myocytes. Wild-type Gαq and Gαq cysteine-to-alanine mutants C9A, C10A, and C9A/C10A were transiently coexpressed in HEK293T cells stably expressing TPα. We examined membrane localization of Gαq, TP receptor-Gαq association by coimmunoprecipitation, and Ca(2+) responses to U46619 in hypoxic and normoxic cells. Gαq palmitoylation is essential for the Ca(2+) response to TPα stimulation. Inhibition of palmitoylation reduces contractile force to thromboxane in PPHN but not in control pulmonary artery. Hypoxia increases palmitoylation of Gαq; the hypoxic. but not the normoxic, response to thromboxane is palmitoylation sensitive. Palmitoylation of one N-terminal cysteine is required for physical association of Gαq with the TPα receptor. Palmitoylation of both cysteines is required for Gαq membrane localization and Ca(2+) mobilization. Depalmitoylation of any one Gαq cysteine reduces the hypoxic response to thromboxane challenge to equal that of normoxic cells.

  19. PGE2 induces IL-6 in orbital fibroblasts through EP2 receptors and increased gene promoter activity: implications to thyroid-associated ophthalmopathy.

    Directory of Open Access Journals (Sweden)

    Nupur Raychaudhuri

    Full Text Available BACKGROUND: IL-6 plays an important role in the pathogenesis of Graves' disease and its orbital component, thyroid-associated ophthalmopathy (TAO. Orbital tissues become inflamed in TAO, a process in which prostanoids have been implicated. Orbital fibroblasts both generate and respond to PGE(2, underlying the inflammatory phenotype of these cells. METHODOLOGY/PRINCIPAL FINDINGS: Using cultured orbital and dermal fibroblasts, we characterized the effects of PGE(2 on IL-6 expression. We found that the prostanoid provokes substantially greater cytokine synthesis in orbital fibroblasts, effects that are mediated through cell-surface EP(2 receptors and increased steady-state IL-6 mRNA levels. The pre-translational up-regulation of IL-6 results from increased gene promoter activity and can be reproduced with the PKA agonist, Sp-cAMP and blocked by interrupting the PKA pathway. PGE(2-induced production of cAMP in orbital fibroblasts was far greater than that in dermal fibroblasts, resulting from higher levels of adenylate cyclase. PGE(2 provokes CREB phosphorylation, increases the pCREB/CREB ratio, and initiates nuclear localization of the pCREB/CREB binding protein/p300 complex (CBP preferentially in orbital fibroblasts. Transfection with siRNAs targeting either CREB or CBP blunts the induction of IL-6 gene expression. PGE(2 promotes the binding of pCREB to its target DNA sequence which is substantially greater in orbital fibroblasts. CONCLUSION/SIGNIFICANCE: These results identify the mechanism underlying the exaggerated induction of IL-6 in orbital fibroblasts and tie together two proinflammatory pathways involved in the pathogenesis of TAO. Moreover, they might therefore define an attractive therapeutic target for the treatment of TAO.

  20. Comprehensive binary interaction mapping of SH2 domains via fluorescence polarization reveals novel functional diversification of ErbB receptors.

    Directory of Open Access Journals (Sweden)

    Ronald J Hause

    Full Text Available First-generation interaction maps of Src homology 2 (SH2 domains with receptor tyrosine kinase (RTK phosphosites have previously been generated using protein microarray (PM technologies. Here, we developed a large-scale fluorescence polarization (FP methodology that was able to characterize interactions between SH2 domains and ErbB receptor phosphosites with higher fidelity and sensitivity than was previously achieved with PMs. We used the FP assay to query the interaction of synthetic phosphopeptides corresponding to 89 ErbB receptor intracellular tyrosine sites against 93 human SH2 domains and 2 phosphotyrosine binding (PTB domains. From 358,944 polarization measurements, the affinities for 1,405 unique biological interactions were determined, 83% of which are novel. In contrast to data from previous reports, our analyses suggested that ErbB2 was not more promiscuous than the other ErbB receptors. Our results showed that each receptor displays unique preferences in the affinity and location of recruited SH2 domains that may contribute to differences in downstream signaling potential. ErbB1 was enriched versus the other receptors for recruitment of domains from RAS GEFs whereas ErbB2 was enriched for recruitment of domains from tyrosine and phosphatidyl inositol phosphatases. ErbB3, the kinase inactive ErbB receptor family member, was predictably enriched for recruitment of domains from phosphatidyl inositol kinases and surprisingly, was enriched for recruitment of domains from tyrosine kinases, cytoskeletal regulatory proteins, and RHO GEFs but depleted for recruitment of domains from phosphatidyl inositol phosphatases. Many novel interactions were also observed with phosphopeptides corresponding to ErbB receptor tyrosines not previously reported to be phosphorylated by mass spectrometry, suggesting the existence of many biologically relevant RTK sites that may be phosphorylated but below the detection threshold of standard mass spectrometry

  1. Potential involvement of P2Y2 receptor in diuresis of postobstructive uropathy in rats.

    Science.gov (United States)

    Zhang, Yue; Kohan, Donald E; Nelson, Raoul D; Carlson, Noel G; Kishore, Bellamkonda K

    2010-03-01

    AVP resistance of the medullary collecting duct (mCD) in postobstructive uropathy (POU) has been attributed to increased production of PGE2. P2Y2 receptor activation causes production of PGE2 by the mCD. We hypothesize that increased P2Y2 receptor expression and/or activity may contribute to the diuresis of POU. Sprague-Dawley rats were subjected to bilateral ureteral obstruction for 24 h followed by release (BUO/R, n = 17) or sham operation (SHM/O, n = 15) and euthanized after 1 wk or 12 days. BUO/R rats developed significant polydipsia, polyuria, urinary concentration defect, and increased urinary PGE2 and decreased aquaporin-2 protein abundance in the inner medulla compared with SHM/O rats. After BUO/R, the relative mRNA expression of P2Y2 and P2Y6 receptors was increased by 2.7- and 4.9-fold, respectively, without significant changes in mRNA expression of P2Y1 or P2Y4 receptor. This was associated with a significant 3.5-fold higher protein abundance of the P2Y2 receptor in BUO/R than SHM/O rats. When freshly isolated mCD fractions were challenged with different types of nucleotides (ATPgammaS, ADP, UTP, or UDP), BUO/R and SHM/O rats responded to only ATPgammaS and UTP and released PGE2, consistent with involvement of the P2Y2, but not P2Y6, receptor. ATPgammaS- or UTP-stimulated increases in PGE2 were much higher in BUO/R (3.20- and 2.28-fold, respectively, vs. vehicle controls) than SHM/O (1.68- and 1.30-fold, respectively, vs. vehicle controls) rats. In addition, there were significant 2.4- and 2.1-fold increases in relative mRNA expression of prostanoid EP1 and EP3 receptors, respectively, in the inner medulla of BUO/R vs. SHM/O rats. Taken together, these data suggest that increased production of PGE2 by the mCD in POU may be due to increased expression and activity of the P2Y2 receptor. Increased mRNA expression of EP1 and EP3 receptors in POU may also help accentuate PGE2-induced signaling in the mCD.

  2. EU-FP7-iMARS: analysis of Mars multi-resolution images using auto-coregistration, data mining and crowd source techniques

    Science.gov (United States)

    Ivanov, Anton; Muller, Jan-Peter; Tao, Yu; Kim, Jung-Rack; Gwinner, Klaus; Van Gasselt, Stephan; Morley, Jeremy; Houghton, Robert; Bamford, Steven; Sidiropoulos, Panagiotis; Fanara, Lida; Waenlish, Marita; Walter, Sebastian; Steinkert, Ralf; Schreiner, Bjorn; Cantini, Federico; Wardlaw, Jessica; Sprinks, James; Giordano, Michele; Marsh, Stuart

    2016-07-01

    Understanding planetary atmosphere-surface and extra-terrestrial-surface formation processes within our Solar System is one of the fundamental goals of planetary science research. There has been a revolution in planetary surface observations over the last 15 years, especially in 3D imaging of surface shape. This has led to the ability to be able to overlay different epochs back in time to the mid 1970s, to examine time-varying changes, such as the recent discovery of mass movement, tracking inter-year seasonal changes and looking for occurrences of fresh craters. Within the EU FP-7 iMars project, UCL have developed a fully automated multi-resolution DTM processing chain, called the Co-registration ASP-Gotcha Optimised (CASP-GO), based on the open source NASA Ames Stereo Pipeline (ASP), which is being applied to the production of planetwide DTMs and ORIs (OrthoRectified Images) from CTX and HiRISE. Alongside the production of individual strip CTX & HiRISE DTMs & ORIs, DLR have processed HRSC mosaics of ORIs and DTMs for complete areas in a consistent manner using photogrammetric bundle block adjustment techniques. A novel automated co-registration and orthorectification chain has been developed and is being applied to level-1 EDR images taken by the 4 NASA orbital cameras since 1976 using the HRSC map products (both mosaics and orbital strips) as a map-base. The project has also included Mars Radar profiles from Mars Express and Mars Reconnaissance Orbiter missions. A webGIS has been developed for displaying this time sequence of imagery and a demonstration will be shown applied to one of the map-sheets. Automated quality control techniques are applied to screen for suitable images and these are extended to detect temporal changes in features on the surface such as mass movements, streaks, spiders, impact craters, CO2 geysers and Swiss Cheese terrain. These data mining techniques are then being employed within a citizen science project within the Zooniverse family

  3. Progress on the calibration of channel geometry and friction parameters of the LISFLOOD-FP hydraulic model using time series of SAR flood images

    Science.gov (United States)

    Wood, M.; Neal, J. C.; Hostache, R.; Corato, G.; Bates, P. D.; Chini, M.; Giustarini, L.; Matgen, P.; Wagener, T.

    2014-12-01

    The objective of this work is to calibrate channel depth and roughness parameters of the LISFLOOD-FP Sub-Grid 2D hydraulic model using SAR image-derived flood extent maps. The aim is to reduce uncertainty in flood model predictions for those rivers where channel geometry is unknown and/or cannot be easily measured. In particular we consider the effectiveness of using real SAR data for calibration and whether the number and timings of SAR acquisitions is of benefit to the final result. Terrain data are processed from 2m LiDAR images and inflows to the model are taken from gauged data. As a test case we applied the method to the River Severn between Worcester and Tewkesbury. We firstly applied the automatic flood mapping algorithm of Giustarini[1] et al. (2013) to ENVISAT ASAR (wide swath mode) flood images; generating a series of flood maps. We then created an ensemble of flood extent maps with the hydraulic model (each model representing a unique parameter set). Where there is a favourable comparison between the modelled flood map and the SAR obtained flood map we may suggest an optimal parameter set. Applying the method to a sequence of SAR acquisitions provides insight into the advantages, disadvantages and limitations of using series of acquired images. To complete the investigation we simultaneously explore parameter 'identifiabilty' within a sequence of available satellite observations by adopting the DYNIA method proposed by Wagener[2] et al. (2003). We show where we might most easily detect the depth and roughness parameters within the SAR acquisition sequence. [1] Giustarini. 2013. 'A Change Detection Approach to Flood Mapping in Urban Areas Using TerraSAR-X'. IEEE Transactions on Geoscience and Remote Sensing, vol. 51, no. 4. [2] Wagener. 2003. 'Towards reduced uncertainty in conceptual rainfall-runoff modelling: Dynamic identifiability analysis'. Hydrol. Process. 17, 455-476.

  4. Study of 5f electron based filled skutterudite compound EuFe{sub 4}Sb{sub 12}, a thermoelectric (TE) material: FP-LAPW method

    Energy Technology Data Exchange (ETDEWEB)

    Shankar, A., E-mail: amitshan2009@gmail.com [Department of Physics, Mizoram University, Aizawl 796004 (India); Rai, D.P., E-mail: dibyaprakashrai@gmail.com [Beijing Computational Science Research Center, 3 Heqing Road, Beijing 100084 (China); Khenata, R. [Laboratoire de Physique Quantique et de Modlisation Mathmatique (LPQ3M), Dpartement de Technologie, Universit de Mascara, 29000 Mascara (Algeria); Maibam, J. [Department of Physics, Assam University, Silchar 788011 (India); Sandeep, E-mail: sndp.chettri@gmail.com [Department of Physics, Mizoram University, Aizawl 796004 (India); Thapa, R.K., E-mail: r.k.thapa@gmail.com [Department of Physics, Mizoram University, Aizawl 796004 (India)

    2015-01-15

    Highlights: • The compound EuFe{sub 4}Sb{sub 12} shows a semi-metallic behavior with pseudo gap. • The inherent dense band near E{sub F} facilitate the charge carriers. • The magnetic moment within LSDA and mBJ are underestimated. • The inclusion of onsite Coulomb repulsion (U) in LSDA has improved the result. • The results obtained from LSDA + U are consistent with the experimental data. - Abstract: We have studied the elastic, electronic and magnetic properties along with the thermoelectric properties of an undoped filled skutterudite EuFe{sub 4}Sb{sub 12} using full-potential linearized augmented plane wave (FP-LAPW) method. The LSDA, LSDA + U and a new exchange-correlation functional called modified Becke Johnson (mBJ) potential based on density functional theory (DFT) were used for studying material properties. The Eu-f and Fe-d are strongly correlated elements thus the inclusion of Coulomb repulsion (U) expected to give an exact ground state properties. The exchange-splitting of Eu-4f states were analyzed to explain the ferromagnetic behavior of EuFe{sub 4}Sb{sub 12} (half-metallic behavior). The numerical values of isotropic elastic parameters and related properties are estimated in the framework of the Voigt–Reuss–Hill approximation. The calculation of thermal transport properties at various temperature shows the high value of Seebeck coefficient and figure of merit (ZT) = 0.25 at room temperature in consistent to the experimental results.

  5. Prediction of phase transition, mechanical and electronic properties of inverse Heusler compound Y2RuPb, via FP-LMTO method

    Science.gov (United States)

    Labair, M.; Rached, H.; Rached, D.; Benalia, S.; Abidri, B.; Khenata, R.; Ahmed, R.; Omran, S. Bin; Bouhemadou, A.; Syrotyuk, S. V.

    2016-03-01

    Topological insulators (TI) are immensely investigated due to their promising characteristics for spintronics and quantum computing applications. In this regard, although bismuth, telluride, selenide and antimony containing compounds are typically considered as topological insulators, materials with Hg2CuTi-type structure have also shown their potential for TIs as well. Here, we present first principles study of the Y2RuPb compound, pertaining to its structural, mechanical, electrical and the optical properties. Calculations are executed at the level of the parameterized Perdew-Burke-Ernzerhof (PBE) generalized gradient approximation (GGA), employing the full-potential (FP) linearized muffin-tin orbital (LMTO) approach, as designed within the density functional theory (DFT). The study is carried out on the Hg2CuTi-type and Cu2MnAl-type structures of the Y2RuPb compound. From our structural calculations, it is found that Y2RuPb is more stable in its Hg2CuTi-type structure; however, the analysis of the mechanical properties reveals its stability in both phases against any kind of elastic deformation. Similarly, Dirac cone shaped surface energy levels found in the predicted electronic band structure of the Y2RuPb compound, and good agreement of the obtained results with Zhang et al., demonstrates that it is a topological insulating material. Additionally, the real and imaginary parts of the dielectric function ɛ (ω) and refractive index n (ω), for an energy range up to 14eV, are analyzed as well.

  6. Effects of doping of calcium atom(s) on structural, electronic and optical properties of binary strontium chalcogenides - A theoretical investigation using DFT based FP-LAPW methodology

    Science.gov (United States)

    Bhattacharjee, Rahul; Chattopadhyaya, Surya

    2017-09-01

    The effects of doping of Ca atom(s) on structural, electronic and optical properties of binary strontium chalcogenide semiconductor compounds have been investigated theoretically using DFT based FP-LAPW approach by modeling the rock-salt (B1) ternary alloys CaxSr1-xS, CaxSr1-xSe and CaxSr1-xTe at some specific concentrations 0 ≤ x ≤ 1 and studying their aforesaid properties. The exchange-correlation potentials for their structural properties have been computed using the Wu-Cohen generalized-gradient approximation (WC-GGA) scheme, while those for the electronic and optical properties have been computed using recently developed Tran-Blaha modified Becke-Johnson (TB-mBJ) scheme. In addition, we have computed the electronic and optical properties with the traditional BLYP and PBE-GGA schemes for comparison. The atomic and orbital origin of different electronic states in the band structure of each of the compounds have been identified from the respective density of states (DOS). Using the approach of Zunger and co-workers, the microscopic origin of band gap bowing has been discussed in term of volume deformation, charge exchange and structural relaxation. Bonding characteristics among the constituent atoms of each of the specimens have been discussed from their charge density contour plots. Optical properties of the binary compounds and ternary alloys have been investigated theoretically in terms of their respective dielectric function, refractive index, normal incidence reflectivity and optical conductivity. Several calculated results have been compared with available experimental and other theoretical data.

  7. Prostaglandin E2 EP4 Receptor Activation Attenuates Neuroinflammation and Early Brain Injury Induced by Subarachnoid Hemorrhage in Rats.

    Science.gov (United States)

    Xu, Jie; Xu, Zhen; Yan, Ai

    2017-02-27

    Activation of E prostanoid 4 receptor (EP4) shows neuroprotective effects in multiple central nervous system (CNS) lesions, but the roles of EP4 receptor in subarachnoid hemorrhage (SAH) are not explored. This study was designed to research the effects of EP4 modulation on early brain injury (EBI) after experimental SAH in rats. We found that the administration of EP4 selective agonist AE1-329 significantly improved neurological dysfunction, blood brain barrier (BBB) damage and brain edema at 24 h after SAH. Furthermore, AE1-329 obviously reduced the number of activated microglia and the mRNA and protein levels of pro-inflammatory cytokines, and increased Ser1177 phosphorylated endothelial nitric oxide synthase (Ser1177 p-eNOS). Moreover, AE1-329 significantly reduced the number of TUNEL-positive cells and active caspase-3 in cortex after SAH. The EP4 selective antagonist AE3-208 was also administrated and the opposite effects were achieved. Our results indicate that activation of EP4 protects brain from EBI through downregulating neuroinflammation reaction after SAH.

  8. Treatment of digital ulcers in systemtic sclerosis with endothelin-1 receptor antagonist (bosentan

    Directory of Open Access Journals (Sweden)

    V. Grattagliano

    2011-09-01

    Full Text Available In systemic sclerosis (SSc occurrence of recurrent digital ulcers (DU is cause of pain and functional disability of hands. Treatment with vasodilator agents, such as calcium channel blockers, ACE inhibitors, prostanoids, has not shown to be an effective therapy. There is evidence that endotelin-1 (ET-1 is a key mediator in regulation of vascular tone and its enhanced production in SSc is believed to lead to vasoconstriction, vessel remodelling, local ischemia and ulcers of fingertips. Recently, an oral endothelin receptor antagonist, bosentan, has been proved to be effective in the treatment of SSc associated pulmonar arterial hypertension (PAH and to decrease the development of new DU in patients with SSc. In this study, we assessed the occurrence of new DU in eight patients with SSc associated PAH and one SSc patient with recurrent DU refractory to standard vasodilatation therapy. All patients received bosentan at dosage of 62.5 mg bid for 4 weeks and 125 mg bid thereafter for one year. All patients had 3-4 DU of hands at baseline and one patients had also ulcers at lower limbs. In seven out of nine patients we did not record the occurrence of new DU and we also observed a 50% reduction of existing DU, whereas new DU occurred only in two patients. These data suggest that ET-1 plays a key role in DU induction in SSc patients and that ET-1 inhibition by bosentan can be an effective therapeutic strategy.

  9. Modeling structure of G protein-coupled receptors in huan genome

    KAUST Repository

    Zhang, Yang

    2016-01-26

    G protein-coupled receptors (or GPCRs) are integral transmembrane proteins responsible to various cellular signal transductions. Human GPCR proteins are encoded by 5% of human genes but account for the targets of 40% of the FDA approved drugs. Due to difficulties in crystallization, experimental structure determination remains extremely difficult for human GPCRs, which have been a major barrier in modern structure-based drug discovery. We proposed a new hybrid protocol, GPCR-I-TASSER, to construct GPCR structure models by integrating experimental mutagenesis data with ab initio transmembrane-helix assembly simulations, assisted by the predicted transmembrane-helix interaction networks. The method was tested in recent community-wide GPCRDock experiments and constructed models with a root mean square deviation 1.26 Å for Dopamine-3 and 2.08 Å for Chemokine-4 receptors in the transmembrane domain regions, which were significantly closer to the native than the best templates available in the PDB. GPCR-I-TASSER has been applied to model all 1,026 putative GPCRs in the human genome, where 923 are found to have correct folds based on the confidence score analysis and mutagenesis data comparison. The successfully modeled GPCRs contain many pharmaceutically important families that do not have previously solved structures, including Trace amine, Prostanoids, Releasing hormones, Melanocortins, Vasopressin and Neuropeptide Y receptors. All the human GPCR models have been made publicly available through the GPCR-HGmod database at http://zhanglab.ccmb.med.umich.edu/GPCR-HGmod/ The results demonstrate new progress on genome-wide structure modeling of transmembrane proteins which should bring useful impact on the effort of GPCR-targeted drug discovery.

  10. EU-FP7-iMARS: analysis of Mars multi-resolution images using auto-coregistration, data mining and crowd source techniques: A Status Report

    Science.gov (United States)

    Muller, Jan-Peter; Sidiropoulos, Panagiotis; Tao, Yu; Gwinner, Klaus; Willner, Konrad; Fanara, Lida; Waehlisch, Marita; Walter, Sebastian; Schreiner, Bjoern; Steikert, Ralf; Ivanov, Anton B.; Cantini, Federico; Wardlaw, Jessica; Sprinks, James Christopher; Giordano, Michele; Kim, Jungrack; Houghton, Robert; Bamford, Steven

    2016-10-01

    al., EPSC16; [11] Campbell, J.et al., EPSC16;[12] Kim, J-R., et al., EPSC16 AcknowledgementsThis research has received funding from the EU's FP7 Programme under iMars 607379. Partial support is also provided from the STFC Grant ST/K000977/1

  11. 2. Annual Workshop Proceedings of the Integrated Project 'Fundamental Processes of Radionuclide Migration' - 6. EC FP IP FUNMIG

    Energy Technology Data Exchange (ETDEWEB)

    Buckau, Gunnar; Kienzler, Bernhard [FZK - Inst. fuer Nukleare Entsorgung, Ka rlsruhe (Germany); Duro, Lara; Montoya, Vanessa [Enviros Spain S.L., Barcelona (Spai n)] (eds.)

    2007-06-15

    Long-term Governance on RAdioactive Waste Management, OBRA Co-ordination Action running from October 2006; Integrated Project PAMINA, running from October 2006; Integrated Project NF-PRO, running from 2004, will finish end of 2007; Treatment of influences of the near field on the geosphere in the Safety Case; Recent developments of the Euratom (Fission) Programme - Priority research area 'Management of Radioactive waste - Disposal of HLW and LLW Towards FP7.

  12. Multiple short-lived stellar prominences on O stars: The O6.5I(n)fp star λ Cephei

    Science.gov (United States)

    Sudnik, N. P.; Henrichs, H. F.

    2016-10-01

    Context. Most O-type stars and many B stars show unexplained cyclical variability in their spectral lines, i.e., modulation on the rotational timescale, but not strictly periodic. The variability occurs in the so-called discrete absorption components (DACs) that accelerate through the UV-wind line profiles and also in many optical lines. For such OB stars no dipolar magnetic fields have been detected with upper limits of ~300 G. Aims: We investigate whether multiple magnetic loops on the surface rather than non-radial pulsations or a dipolar magnetic field can explain the observed cyclical UV and optical spectral line variability. Methods: We present time-resolved, high-resolution optical spectroscopy of the O6.5I(n)fp star λ Cephei. We apply a simplified phenomenological model in which multiple spherical blobs attached to the surface represent magnetic-loop structures, which we call stellar prominences, by analogy with solar prominences. We compare the calculated line profiles as a function of rotational phase, adopting a rotation period of 4.1 d, with observed relative changes in subsequent quotient spectra. Results: We identify many periodicities in spectral lines, almost none of which is stable over timescales from months to years. We show that the relative changes in various optical absorption and emission lines are often very similar. Our proposed model applied to the He ii λ4686 line can typically be fitted with 2-5 equatorial blobs with lifetimes between ~1 and 24 h. Conclusions: Given the irregular timescales involved, we propose that the azimuthal distribution of DACs correspond to the locations of stellar prominences attached to the surface. This could explain the observed variability of optical and UV lines, and put constraints on the strength and lifetime of these structures, which can be compared with recent theoretical predictions, in which bright magnetic surface spots are formed by the action of the subsurface convection zone. Based on

  13. The European FP7 ULTimateCO2 project: A comprehensive approach to study the long term fate of CO2 geological storage sites

    Science.gov (United States)

    Audigane, P.; Brown, S.; Dimier, A.; Pearce, J.; Frykman, P.; Maurand, N.; Le Gallo, Y.; Spiers, C. J.; Cremer, H.; Rutters, H.; Yalamas, T.

    2013-12-01

    The European FP7 ULTimateCO2 project aims at significantly advance our knowledge of specific processes that could influence the long-term fate of geologically stored CO2: i) trapping mechanisms, ii) fluid-rock interactions and effects on mechanical integrity of fractured caprock and faulted systems and iii) leakage due to mechanical and chemical damage in the well vicinity, iv) brine displacement and fluid mixing at regional scale. A realistic framework is ensured through collaboration with two demonstration sites in deep saline sandstone formations: the onshore former NER300 West Lorraine candidate in France (ArcelorMittal GeoLorraine) and the offshore EEPR Don Valley (former Hatfield) site in UK operated by National Grid. Static earth models have been generated at reservoir and basin scale to evaluate both trapping mechanisms and fluid displacement at short (injection) and long (post injection) time scales. Geochemical trapping and reservoir behaviour is addressed through experimental approaches using sandstone core materials in batch reactive mode with CO2 and impurities at reservoir pressure and temperature conditions and through geochemical simulations. Collection of data has been generated from natural and industrial (oil industry) analogues on the fluid flow and mechanical properties, structure, and mineralogy of faults and fractures that could affect the long-term storage capacity of underground CO2 storage sites. Three inter-related lines of laboratory experiments investigate the long-term evolution of the mechanical properties and sealing integrity of fractured and faulted caprocks using Opalinus clay of Mont Terri Gallery (Switzerland) (OPA), an analogue for caprock well investigated in the past for nuclear waste disposal purpose: - Characterization of elastic parameters in intact samples by measuring strain during an axial experiment, - A recording of hydraulic fracture flow properties by loading and shearing samples in order to create a 'realistic

  14. Involvement of the prostaglandin E receptor EP2 in paeoniflorin-induced human hepatoma cell apoptosis.

    Science.gov (United States)

    Hu, Shanshan; Sun, Wuyi; Wei, Wei; Wang, Di; Jin, Juan; Wu, Jingjing; Chen, Jingyu; Wu, Huaxun; Wang, Qingtong

    2013-02-01

    Prostaglandin E2 (PGE2) has been shown to play an important role in tumor development and progression. PGE2 mediates its biological activity by binding any one of four prostanoid receptors (EP1 through EP4). The present study was designed to determine the role of the EP2 receptor during the proliferation and apoptosis of human HepG2 and SMMC-7721 hepatoma cell lines and the effect of paeoniflorin, a monoterpene glycoside. The proliferation of HepG2 and SMMC-7721 cells was determined by methyl thiazolyl tetrazolium after exposure to the selective EP2 receptor agonists butaprost and paeoniflorin. Apoptosis of HepG2 and SMMC-7721 cells was also quantified by flow cytometry with annexin V-fluorescein isothiocyanate and propidium iodide staining. The expression levels of Bcl-2 and Bax were quantified by western blotting and immunohistochemistry. The expression of the EP2 receptor and cysteine-aspartic acid protease (caspase)-3 was determined by western blotting. Butaprost significantly increased proliferation in HepG2 and SMMC-7721 cells. Paeoniflorin significantly inhibited the proliferation of HepG2 and SMMC-7721 cells stimulated by butaprost at multiple time points (24, 48, and 72 h). Paeoniflorin induced apoptosis in HepG2 and SMMC-7721 cells, which was quantified by annexin-V and propidium iodide staining. Our results indicate that the expression of the EP2 receptor and Bcl-2 was significantly increased, whereas that of Bax and cleaved caspase-3 was decreased in HepG2 and SMMC-7721 cells after stimulation by butaprost. Paeoniflorin significantly decreased the expression of the EP2 receptor and Bcl-2 and increased Bax and caspase-3 activation in HepG2 and SMMC-7721 cells on addition of butaprost. Our results show that the PGE2 receptor subtype EP2 may play a vital role in the survival of both HepG2 and SMMC-7721 cells. Paeoniflorin, which may be a promising agent in the treatment of liver cancer, induced apoptosis in hepatocellular carcinoma cells by downregulating

  15. Nicotinic acetylcholine receptor α7 subunits with a C2 cytoplasmic loop yellow fluorescent protein insertion form functional receptors

    Institute of Scientific and Technical Information of China (English)

    Teresa A MURRAY; Qiang LIU; Paul WHITEAKER; Jie WU; Ronald J LUKAS

    2009-01-01

    Aim: Several nicotinic acetylcholine receptor (nAChR) subunits have been engineered as fluorescent protein (FP) fusions and exploited to illuminate features of nAChRs. The aim of this work was to create a FP fusion in the nAChR a.7 subunit without compromising formation of functional receptors.Methods: A gene construct was generated to introduce yellow fluorescent protein (YFP), in frame, into the otherwise unaltered, large, second cytoplamsic loop between the third and fourth transmembrane domains of the mouse nAChR al sub-unit (a7Y). SH-EP1 cells were transfected with mouse nAChR wild type a.7 subunits (a.7) or with a7Y subunits, alone or with the chaperone protein, hRJC-3. Receptor function was assessed using whole-cell current recording. Receptor expression was measured with 125I-labeled a-bungarotoxin (I-Bgt) binding, laser scanning confocal microscopy, and total internal reflectance fluorescence (TIRF) microscopy.Results: Whole-cell currents revealed that a7Y nAChRs and al nAChRs were functional with comparable EC50 values for the a7 nAChR-selective agonist, choline, and IC50 values for the a.7 nAChR-selective antagonist, methyllycaconitine. I-Bgt binding was detected only after co-expression with hRIC-3. Confocal microscopy revealed that a7Y had primarily intracel-lular rather than surface expression. TIRF microscopy confirmed that little a7Y localized to the plasma membrane, typical of a7 nAChRs.Conclusion: nAChRs composed as homooligomers of a7Y subunits containing cytoplasmic loop YFP have functional, ligand binding, and trafficking characteristics similar to those of a.7 nAChRs. a7Y nAChRs may be used to elucidate properties of a.7 nAChRs and to identify and develop novel probes for these receptors, perhaps in high-throughput fashion.

  16. Endogenous competition against binding of [(18)F]DMFP and [(18)F]fallypride to dopamine D(2/3) receptors in brain of living mouse.

    Science.gov (United States)

    Rominger, Axel; Wagner, Erika; Mille, Erik; Böning, Guido; Esmaeilzadeh, Mouna; Wängler, Björn; Gildehaus, Franz-Josef; Nowak, Sebastian; Bruche, Ariane; Tatsch, Klaus; Bartenstein, Peter; Cumming, Paul

    2010-04-01

    Molecular imaging studies with benzamide radioligands can reveal competition from endogenous binding at D(2/3)-receptors in living brain. However, single photon emission computed tomography (SPECT) methods suffer from limited spatial resolution, and [(11)C]-labeled ligands are only available at positron emission tomography (PET) research sites with cyclotron-radiochemistry facilities, whereas [(18)F] can be transported, due to its longer physical half-life. Therefore, we endeavored to characterize the vulnerabilities of the benzamide antagonist [(18)F]desmethoxyfallypride (DMFP) and its high-affinity congener [(18)F]fallypride (FP) to competition from endogenous dopamine in living mouse brain. Groups of awake mice were pretreated with saline, amphetamine (10 mg/kg), or reserpine (5 mg/kg), followed by i.v. tracer injections. Mice were killed at 2.5-90 min (DMFP) or 2.5-180 min (FP) circulation times. Brains were dissected and regional radioactivity concentration measured by gamma counting. Other groups of mice were anesthetized for dynamic microPET recordings with DMFP or FP. Binding potentials (BP(ND)) were calculated using cerebellum as reference region. With 90-min circulation, DMFP BP(ND) in striatum was 2.4 by dissection and 2.2 by microPET, which showed a 62% decrease in response to amphetamine-evoked dopamine release and a 33% increase after reserpine-evoked dopamine depletion. With 120-min circulation, FP BP(ND) in striatum was 24.1 by dissection and 9.2 by microPET, which showed a 31% decrease in the amphetamine group, but no effect of reserpine. Dissection showed similar sensitivities for FP binding, but only a 29% amphetamine-evoked reduction for DMFP. Relative to gold standard ex vivo results, microPET estimates of DMFP BP(ND) were unbiased, whereas FP BP(ND) in striatum was substantially underestimated. Both tracers proved suitable for revealing pharmacologically evoked changes in competition at D(2/3)-receptors in striatum of living mice.

  17. Suppression of inflammation with conditional deletion of the prostaglandin E2 EP2 receptor in macrophages and brain microglia.

    Science.gov (United States)

    Johansson, Jenny U; Pradhan, Suraj; Lokteva, Ludmila A; Woodling, Nathaniel S; Ko, Novie; Brown, Holden D; Wang, Qian; Loh, Christina; Cekanaviciute, Egle; Buckwalter, Marion; Manning-Bog, Amy B; Andreasson, Katrin I

    2013-10-02

    Prostaglandin E2 (PGE2), a potent lipid signaling molecule, modulates inflammatory responses through activation of downstream G-protein coupled EP(1-4) receptors. Here, we investigated the cell-specific in vivo function of PGE2 signaling through its E-prostanoid 2 (EP2) receptor in murine innate immune responses systemically and in the CNS. In vivo, systemic administration of lipopolysaccharide (LPS) resulted in a broad induction of cytokines and chemokines in plasma that was significantly attenuated in EP2-deficient mice. Ex vivo stimulation of peritoneal macrophages with LPS elicited proinflammatory responses that were dependent on EP2 signaling and that overlapped with in vivo plasma findings, suggesting that myeloid-lineage EP2 signaling is a major effector of innate immune responses. Conditional deletion of the EP2 receptor in myeloid lineage cells in Cd11bCre;EP2(lox/lox) mice attenuated plasma inflammatory responses and transmission of systemic inflammation to the brain was inhibited, with decreased hippocampal inflammatory gene expression and cerebral cortical levels of IL-6. Conditional deletion of EP2 significantly blunted microglial and astrocytic inflammatory responses to the neurotoxin MPTP and reduced striatal dopamine turnover. Suppression of microglial EP2 signaling also increased numbers of dopaminergic (DA) neurons in the substantia nigra independent of MPTP treatment, suggesting that microglial EP2 may influence development or survival of DA neurons. Unbiased microarray analysis of microglia isolated from adult Cd11bCre;EP2(lox/lox) and control mice demonstrated a broad downregulation of inflammatory pathways with ablation of microglial EP2 receptor. Together, these data identify a cell-specific proinflammatory role for macrophage/microglial EP2 signaling in innate immune responses systemically and in brain.

  18. Prostaglandin E2 EP2 Receptor Deletion Attenuates Intracerebral Hemorrhage-Induced Brain Injury and Improves Functional Recovery

    Directory of Open Access Journals (Sweden)

    Jenna L. Leclerc

    2015-04-01

    Full Text Available Intracerebral hemorrhage (ICH is a devastating type of stroke characterized by bleeding into the brain parenchyma and secondary brain injury resulting from strong neuroinflammatory responses to blood components. Production of prostaglandin E2 (PGE2 is significantly upregulated following ICH and contributes to this inflammatory response in part through its E prostanoid receptor subtype 2 (EP2. Signaling through the EP2 receptor has been shown to affect outcomes of many acute and chronic neurological disorders; although, not yet explored in the context of ICH. Wildtype (WT and EP2 receptor knockout (EP2−/− mice were subjected to ICH, and various anatomical and functional outcomes were assessed by histology and neurobehavioral testing, respectively. When compared with age-matched WT controls, EP2−/− mice had 41.9 ± 4.7% smaller ICH-induced brain lesions and displayed significantly less ipsilateral hemispheric enlargement and incidence of intraventricular hemorrhage. Anatomical outcomes correlated with improved functional recovery as identified by neurological deficit scoring. Histological staining was performed to begin investigating the mechanisms involved in EP2-mediated neurotoxicity after ICH. EP2−/− mice exhibited 45.5 ± 5.8% and 41.4 ± 8.1% less blood and ferric iron accumulation, respectively. Furthermore, significantly less striatal and cortical microgliosis, striatal and cortical astrogliosis, blood–brain barrier breakdown, and peripheral neutrophil infiltration were seen in EP2−/− mice. This study is the first to suggest a deleterious role for the PGE2-EP2 signaling axis in modulating brain injury, inflammation, and functional recovery following ICH. Targeting the EP2 G protein-coupled receptor may represent a new therapeutic avenue for the treatment of hemorrhagic stroke.

  19. A midline switch of receptor processing regulates commissural axon guidance in vertebrates

    Science.gov (United States)

    Nawabi, Homaira; Briançon-Marjollet, Anne; Clark, Christopher; Sanyas, Isabelle; Takamatsu, Hyota; Okuno, Tatsusada; Kumanogoh, Atsushi; Bozon, Muriel; Takeshima, Kaori; Yoshida, Yutaka; Moret, Frédéric; Abouzid, Karima; Castellani, Valérie

    2010-01-01

    Commissural axon guidance requires complex modulations of growth cone sensitivity to midline-derived cues, but underlying mechanisms in vertebrates remain largely unknown. By using combinations of ex vivo and in vivo approaches, we uncovered a molecular pathway controlling the gain of response to a midline repellent, Semaphorin3B (Sema3B). First, we provide evidence that Semaphorin3B/Plexin-A1 signaling participates in the guidance of commissural projections at the vertebrate ventral midline. Second, we show that, at the precrossing stage, commissural neurons synthesize the Neuropilin-2 and Plexin-A1 Semaphorin3B receptor subunits, but Plexin-A1 expression is prevented by a calpain1-mediated processing, resulting in silencing commissural responsiveness. Third, we report that, during floor plate (FP) in-growth, calpain1 activity is suppressed by local signals, allowing Plexin-A1 accumulation in the growth cone and sensitization to Sema3B. Finally, we show that the FP cue NrCAM mediates the switch of Plexin-A1 processing underlying growth cone sensitization to Sema3B. This reveals pathway-dependent modulation of guidance receptor processing as a novel mechanism for regulating guidance decisions at intermediate targets. PMID:20159958

  20. The androgen receptor and estrogen receptor

    NARCIS (Netherlands)

    Oosterkamp, H.M.; Bernards, R.A.

    2002-01-01

    The androgen receptor (AR) and the estrogen receptors (ER) are members of the nuclear receptor (NR) family. These NRs are distinguished from the other transcription factors by their ability to control gene expression upon ligand binding (steroids, retinoids, thyroid hormone, vitamin D, fatty acids,