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Sample records for leukotrienes lt b4

  1. Verification of the production of peptide leukotrienes (LT) in traumatic shock

    International Nuclear Information System (INIS)

    Hock, C.E.; Craft, D.V.; Lefer, D.J.; Lefer, A.M.

    1986-01-01

    Both lipoxygenase inhibition and leukotriene receptor antagonism have been demonstrated to provide significant protection in traumatic shock. Despite these findings, leukotrienes have not been found in circulating blood in Noble-Collip drum induced traumatic shock using radioimmunoassay techniques. Anesthetized rats subjected to Noble-Collip drum trauma developed a shock state characterized by a significant reduction in mean arterial blood pressure, a 4.5 fold increase in plasma cathepsin D activity, a 3-fold increase in myocardial depressant factor activity and a mean survival time of 1.9 +/- 0.3 hours. Plasma and bile samples were analyzed by reverse phase high pressure liquid chromatography to determine LT production in this shock model. No detectable peptide leukotrienes or their metabolites were found in plasma. The major peptide leukotriene from bile eluted between LTC 4 and LTD 4 and corresponds to a metabolite of LTE 4 , N-acetyl-LTE 4 . This metabolite increased from 6 +/- 3 to 41 +/- 4 units in traumatic shock when compared to sham trauma (p 4 , LTD 4 and LTE 4 (10 μg/kg/h) also resulted in the metabolism of > 90% of the parent LT to this metabolite in bile. Therefore, plasma LTs accumulate in the bile following trauma in rats. Moreover, LTC 4 , LTD 4 and LTE 4 apparently are rapidly metabolized to N-acetyl LTE 4 . These findings further support a role for leukotrienes in the pathogenesis of traumatic shock in rats

  2. Carbon monoxide inhibits omega-oxidation of leukotriene B4 by human polymorphonuclear leukocytes: evidence that catabolism of leukotriene B4 is mediated by a cytochrome P-450 enzyme.

    Science.gov (United States)

    Shak, S; Goldstein, I M

    1984-09-17

    Carbon monoxide significantly inhibits omega-oxidation of exogenous leukotriene B4 to 20-OH-leukotriene B4 and 20-COOH-leukotriene B4 by unstimulated polymorphonuclear leukocytes as well as omega-oxidation of leukotriene B4 that is generated when cells are stimulated with the calcium ionophore, A23187. Inhibition of omega-oxidation by carbon monoxide is concentration-dependent, completely reversible, and specific. Carbon monoxide does not affect synthesis of leukotriene B4 by stimulated polymorphonuclear leukocytes or other cell functions (i.e., degranulation, superoxide anion generation). These findings suggest that a cytochrome P-450 enzyme in human polymorphonuclear leukocytes is responsible for catabolizing leukotriene B4 by omega-oxidation.

  3. Mass spectrometry and metabolism of leukotriene B4

    International Nuclear Information System (INIS)

    Harper, T.W.

    1985-01-01

    Leukotriene B 4 (LTB 4 ) is a potent and powerful chemotactic factor for polymorphonuclear leukocytes and has been hypothesized to play a role as a mediator of the inflammatory response. A cell free system capable of generating leukotrienes from exogenous arachidonic acid was developed using both rat basophilic leukemia cells and murine mastocytoma cells. The cell free leukotriene generating system was used to prepare leukotrienes for mass spectral studies using electron impact (EI), chemical ionization (Cl), negative ion chemical ionization (NCl) and both positive and negative ion fast atom bombardment mass spectrometry (FAB-MS). Although all of the techniques examined yielded useful information, NCl was found to be the most useful for sensitive quantitation of leukotrienes, whereas Cl and El are more useful for unambiguous structural characterization of hydroxy fatty acid leukotrienes. Investigation of the in vivo metabolism of LTB 4 in the mouse and guinea pig indicated that less than 10% of the injected radiolabel from 3 H-LTB 4 was excreted via the urine and feces. Approximately 30% of the urinary radioactivity was volatile, probably due to loss of the tritium label as water. In the monkey, approximately 10% of the injected radiolabel from 14 C-LTB 4 was excreted in the urine within 5 1/2 hours. In this study, approximately 10% of the urinary radiolabel was volatile, with a large number of unidentified non-volatile products also observed. The isolated perfused rat lung was found to rapidly metabolize leukotriene C 4 to leukotrienes D 4 and E 4 and to leukotriene C 4 sulfoxide

  4. The Leukotriene B4/BLT1 Axis Is a Key Determinant in Susceptibility and Resistance to Histoplasmosis

    Science.gov (United States)

    Secatto, Adriana; Soares, Elyara Maria; Locachevic, Gisele Aparecida; Assis, Patricia Aparecida; Paula-Silva, Francisco Wanderlei Garcia; Serezani, Carlos Henrique; de Medeiros, Alexandra Ivo; Faccioli, Lúcia Helena

    2014-01-01

    The bioactive lipid mediator leukotriene B4 (LTB4) greatly enhances phagocyte antimicrobial functions against a myriad of pathogens. In murine histoplasmosis, inhibition of the LT-generating enzyme 5-lypoxigenase (5-LO) increases the susceptibility of the host to infection. In this study, we investigated whether murine resistance or susceptibility to Histoplasma capsulatum infection is associated with leukotriene production and an enhancement of in vivo and/or in vitro antimicrobial effector function. We show that susceptible C57BL/6 mice exhibit a higher fungal burden in the lung and spleen, increased mortality, lower expression levels of 5-LO and leukotriene B4 receptor 1 (BLT1) and decreased LTB4 production compared to the resistant 129/Sv mice. Moreover, we demonstrate that endogenous and exogenous LTs are required for the optimal phagocytosis of H. capsulatum by macrophages from both murine strains, although C57BL/6 macrophages are more sensitive to the effects of LTB4 than 129/Sv macrophages. Therefore, our results provide novel evidence that LTB4 production and BLT1 signaling are required for a histoplasmosis-resistant phenotype. PMID:24465479

  5. Leukotriene E4 induces airflow obstruction and mast cell activation through the cysteinyl leukotriene type 1 receptor.

    Science.gov (United States)

    Lazarinis, Nikolaos; Bood, Johan; Gomez, Cristina; Kolmert, Johan; Lantz, Ann-Sofie; Gyllfors, Pär; Davis, Andy; Wheelock, Craig E; Dahlén, Sven-Erik; Dahlén, Barbro

    2018-03-05

    Leukotriene (LT) E 4 is the final active metabolite among the cysteinyl leukotrienes (CysLTs). Animal studies have identified a distinct LTE 4 receptor, suggesting that current cysteinyl leukotriene type 1 (CysLT 1 ) receptor antagonists can provide incomplete inhibition of CysLT responses. We tested this hypothesis by assessing the influence of the CysLT 1 antagonist montelukast on responses induced by means of inhalation of LTE 4 in asthmatic patients. Fourteen patients with mild intermittent asthma and 2 patients with aspirin-exacerbated respiratory disease received 20 mg of montelukast twice daily and placebo for 5 to 7 days in a randomized, double-blind, crossover study (NCT01841164). The PD 20 value was determined at the end of each treatment period based on an increasing dose challenge. Measurements included lipid mediators in urine and sputum cells 4 hours after LTE 4 challenge. Montelukast completely blocked LTE 4 -induced bronchoconstriction. Despite tolerating an at least 10 times higher dose of LTE 4 after montelukast, there was no difference in the percentage of eosinophils in sputum. Urinary excretion of all major lipid mediators increased after LTE 4 inhalation. Montelukast blocked release of the mast cell product prostaglandin (PG) D 2 , as well as release of PGF 2α and thromboxane (Tx) A 2 , but not increased excretion of PGE 2 and its metabolites or isoprostanes. LTE 4 induces airflow obstruction and mast cell activation through the CysLT 1 receptor. Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  6. Development of a sensitive and specific radioreceptor assay for leukotriene B4

    International Nuclear Information System (INIS)

    Kohi, F.; Agrawal, D.K.; Cheng, J.B.; Bewtra, A.; Townley, R.G.; Olesch, J.W.

    1988-01-01

    To establish a simple and sensitive quantitation of leukotriene B 4 (LTB 4 ), they developed a radioreceptor assay (RRA) using a highly specific [ 3 H]leukotriene B 4 ([ 3 H]LTB 4 ) binding to a guinea pig spleen homogenate. The assay detected LTB 4 levels as low as 0.12 pmol per tube. 50% inhibition of bound [ 3 H]LTB 4 was obtained by 2.5 nM of unlabeled LTB 4 . [ 3 H]LTB 4 competition studies indicated that 20-hydroxy-LTB 4 was 8 times, 6 trans-LTB 4 was 640 times and 20-carboxy-LTB 4 was 1000 times less effective than LTB 4 . The peptide leukotrienes C 4 , D 4 and E 4 showed no effect on [ 3 H]LTB 4 binding. Recovery rates averaged 97% after ethanol extraction and evaporation of known amounts of LTB 4 . The intra-assay coefficients of variation for three samples were 2.4%, 7.2% and 8.4%, respectively. This assay was validated by measuring LTB 4 released from human granulocytes stimulated with calcium ionophore A23187. The LTB 4 level was maximal at 10 min and decreased rapidly after 15 min. This radioreceptor assay for leukotriene B 4 is highly sensitive and is comparable to the reported sensitivity by radioimmunoassay. The method is simpler and less expensive than other methods such as high pressure liquid chromatography and is suitable for routine measurement of leukotriene B 4

  7. Selectivity of recombinant human leukotriene D(4), leukotriene B(4), and lipoxin A(4) receptors with aspirin-triggered 15-epi-LXA(4) and regulation of vascular and inflammatory responses.

    Science.gov (United States)

    Gronert, K; Martinsson-Niskanen, T; Ravasi, S; Chiang, N; Serhan, C N

    2001-01-01

    Aspirin-triggered lipoxin A(4) (ATL, 15-epi-LXA(4)) and leukotriene D(4) (LTD(4)) possess opposing vascular actions mediated via receptors distinct from the LXA(4) receptor (ALX) that is involved in leukocyte trafficking. Here, we identified these receptors by nucleotide sequencing and demonstrate that LTD(4) receptor (CysLT(1)) is induced in human vascular endothelia by interleukin-1beta. Recombinant CysLT(1) receptor gave stereospecific binding with both [(3)H]-LTD(4) and a novel labeled mimetic of ATL ([(3)H]-ATLa) that was displaced with LTD(4) and ATLa ( approximately IC(50) 0.2 to 0.9 nmol/L), but not with a bioinactive ATL isomer. The clinically used CysLT(1) receptor antagonist, Singulair, showed a lower rank order for competition with [(3)H]-ATLa (IC(50) approximately 8.3 nmol/L). In contrast, LTD(4) was an ineffective competitive ligand for recombinant ALX receptor with [(3)H]-ATLa, and ATLa did not compete for [(3)H]-LTB(4) binding with recombinant LTB(4) receptor. Endogenous murine CysLT(1) receptors also gave specific [(3)H]-ATLa binding that was displaced with essentially equal affinity by LTD(4) or ATLa. Systemic ATLa proved to be a potent inhibitor (>50%) of CysLT(1)-mediated vascular leakage in murine skin (200 microg/kg) in addition to its ability to block polymorphonuclear leukocyte recruitment to dorsal air pouch (4 microg/kg). These results indicate that ATL and LTD(4) bind and compete with equal affinity at CysLT(1), providing a molecular basis for aspirin-triggered LXs serving as a local damper of both vascular CysLT(1) signals as well as ALX receptor-regulated polymorphonuclear leukocyte traffic.

  8. (3H)leukotriene B4 binding to the guinea pig spleen membranes: a rich tissue source for a high affinity leukotriene B4 receptor site

    International Nuclear Information System (INIS)

    Cheng, J.B.; Kohi, F.; Townley, R.G.

    1986-01-01

    To select a tissue rich for the high affinity leukotriene (LT)B 4 receptor site, they compared binding of 1 nM ( 3 H)LTB 4 (180 Ci/mmol) to the crude membrane preparations of guinea pig spleen, thymus, lung, uterus, bladder, brain, adrenal gland, small intestine, liver, kidney and heart. They found that the membrane preparations from spleen contained the highest binding activity per mg protein. They characterized the LTB 4 binding to the spleen preparation in detail. LTB 4 binding was rapid, reversible, stereoselective and saturable. The data from equilibrium experiments showed a linear Scatchard plot with a K/sub d/ of 1.6 nM and a binding site density of 259 fmol/mg prot. The rank order of agents competing for spleen ( 3 H)LTB 4 binding at 25 0 C was: LTB 4 (K/sub i/ = 2.8 nM) > 20-OH-LTB 4 (23 nM) > LTA 4 (48 nM) > LTA 4 methyl ester (0.13 μM) > 20-COOH-LTB 4 (> 6.6 μM) ≥ arachidonic acid (0.15 mM) similarly ordered FPL-55,712 (0.11 mM). At 4 0 C, LTB 4 (2.3 nM) competed at least 10x more effectively than 20-OH-LTB 4 (29 nM) and 20-COOH-LTB 4 (> 6.6 μM). HPLC analysis indicated that incubation of 84 ng LTB 4 with the spleen membrane at 25 0 C did not result in the formation of 20-OH-LTB 4 ( 3 H)LTB 4 receptor binding sites

  9. Leukotriene D4 induces chemotaxis in human eosinophilc cell line, EoL-1 cells via CysLT1 receptor activation.

    Science.gov (United States)

    Shirasaki, Hideaki; Kanaizumi, Etsuko; Himi, Tetsuo

    2017-11-01

    Numerous reports have shown that cysteinyl leukotrienes (CysLTs) contribute to tissue accumulation of eosinophils in allergic airway inflammation. To date, only a few studies have reported that CysLTs promote chemotactic activity of human eosinophils in vitro. The purpose of this study was to investigate whether CysLTs promote chemotaxis in the human eosinophilic cell line, EoL-1. EoL-1 cells were induced to differentiate into mature eosinophil-like cells via incubation with butyric acid and cytokines (IL-3, IL-5 and GM-CSF). The chemotactic activity of the differentiated EoL-1 cells was assessed using the commercial cell migration assay kit. LTD 4 elicited dose-related chemotactic activity in the differntiated EoL-1 cells in the range of 1-100 nM. A typical bell-shaped dose-response curve was observed with optimal activity at 10 nM. The chemotactic activity elicited by LTD 4 (10 nM) was significantly inhibited by montelukast (control, 345 ± 19.2 × 10 3 RFU; LTD 4 10 nM alone, 511 ± 39.2 × 10 3 RFU; LTD 4 10 nM plus montelukast 100 nM, 387 ± 28.2 × 10 3 RFU). LTD 4 induces migration in eosinophilic cells via activation of CysLT1 receptor. The present in vitro model may be useful for elucidation of the mechanism underlying CysLT-induced tissue eosinophilia.

  10. Ligand-induced tyrosine phosphorylation of cysteinyl leukotriene receptor 1 triggers internalization and signaling in intestinal epithelial cells

    DEFF Research Database (Denmark)

    Parhamifar, Ladan; Sime, Wondossen; Yudina, Yuliana

    2010-01-01

    Leukotriene D(4) (LTD(4)) belongs to the bioactive lipid group known as eicosanoids and has implications in pathological processes such as inflammation and cancer. Leukotriene D(4) exerts its effects mainly through two different G-protein-coupled receptors, CysLT(1) and CysLT(2). The high affinit...

  11. [Leukotriene antagonists: a new approach in the treatment of asthma].

    Science.gov (United States)

    Devillier, P; Bessard, G; Advenier, C

    1997-06-01

    Inflammation plays an essential role in the genesis of airflow obstruction and bronchial hyper-reactivity in the early stages of clinical asthma. The treatment of bronchial inflammation has become an essential element in the therapeutic strategy and principally rests on inhaled glucocorticoids. Amongst a number of inflammatory mediators leukotrienes occupy a privileged place by the power of their inflammatory and constrictor effects on bronchial smooth muscles. These properties have justified the clinical development of inhibitors of their synthesis and of specific antagonists to their receptors. Leukotriene antagonists are specific for a sub type of leukotriene receptors C4, D4 and E4 which is implicated in the majority of the bronchial constrictor and inflammatory effects of leukotrienes. The antagonists of Cys-LT1 receptor but also the inhibitors of the leukotriene synthesis exert an additive bronchodilator effect to those of B2 stimulants confirming an efficacious protection vis a vis bronchial provocation tests and above all they improve the clinical scores, lung function and also enable a decrease in the consumption of beta 2 agonists. The marketing of these products represents a major event because it corresponds to the advent of a new therapeutic class. The ease of administration by the oral route, their demonstrated efficacy and their good tolerance profile (in particular for ICI 204.219, and antagonists to Cys-LT1 receptors) are elements which foresee a success for this new asthmatic treatment. However numerous studies, notably comparative studies vis a vis reference treatments will be necessary to define their place in the strategic approach to the treatment of asthma.

  12. The Role of Leukotriene B4 in Allergic Diseases

    Directory of Open Access Journals (Sweden)

    Hiroshi Ohnishi

    2008-01-01

    Full Text Available Leukotriene B4 (LTB4 is a lipid mediator with potent chemoattractant properties and that is rapidly generated from activated innate immune cells such as neutrophils, macrophages, and mast cells. Elevated levels of LTB4 have been reported in various allergic diseases and these levels have been related to disease activity and response to treatment. Recent studies using LTB4 receptor-1 (BLT1 antagonists or BLT1-deficient mice have revealed that ligation of BLT1 by LTB4 is important for the activation and recruitment of inflammatory cells including neutrophils, eosinophils, monocytes/macrophages, mast cells, dendritic cells, and more recently, effector T cells to inflamed tissues in various inflammatory diseases. The LTB4/BLT1 pathway appears to play an important role in the pathogenesis of severe persistent asthma, aspirin- and exercise-induced asthma, allergic rhinitis, and atopic dermatitis together with other mediators including cysteinyl leukotrienes, cytokines, and chemokines. LTB4 production is in general resistant to corticosteroid treatment. In fact, corticosteroids can upregulate BLT1 expression on corticosteroid-resistant inflammatory cells such as neutrophils, monocytes, and effector memory CD8+ T cells. As a result, this corticosteroid-resistant LTB4/BLT1 pathway may contribute to the development of inflammation in allergic diseases that do not respond to the introduction of corticosteroids. Inhibition of this pathway has potential therapeutic benefit in various allergic diseases that have involvement of corticosteroid-insensitivity.

  13. The inflammatory mediator leukotriene D4 induces subcellular β-catenin translocation and migration of colon cancer cells

    International Nuclear Information System (INIS)

    Salim, Tavga; Sand-Dejmek, Janna; Sjölander, Anita

    2014-01-01

    The abnormal activation of the Wnt/β-catenin pathway frequently occurs in colorectal cancer. The nuclear translocation of β-catenin activates the transcription of target genes that promote cell proliferation, survival, and invasion. The pro-inflammatory mediator leukotriene D 4 (LTD 4 ) exerts its effects through the CysLT 1 receptor. We previously reported an upregulation of CysLT 1 R in patients with colon cancer, suggesting the importance of leukotrienes in colon cancer. The aim of this study was to investigate the impact of LTD 4 on Wnt/β-catenin signaling and its effects on proliferation and migration of colon cancer cells. LTD 4 stimulation led to an increase in β-catenin expression, β-catenin nuclear translocation and the subsequent transcription of MYC and CCND1. Furthermore, LTD 4 significantly reduced the expression of E-cadherin and β-catenin at the plasma membrane and increased the migration and proliferation of HCT116 colon cancer cells. The effects of LTD 4 can be blocked by the inhibition of CysLT 1 R. Furthermore, LTD 4 induced the inhibition of glycogen synthase kinase 3 (GSK)-3β activity, indicating a crosstalk between the G-protein-coupled receptor CysLT 1 and the Wnt/β-catenin pathway. In conclusion, LTD 4 , which can be secreted from macrophages and leukocytes in the tumor microenvironment, induces β-catenin translocation and the activation of β-catenin target genes, resulting in the increased proliferation and migration of colon cancer cells. - Highlights: • Leukotriene D 4 (LTD 4 ) lowers membrane β-catenin but increases nuclear β-catenin levels in colon cancer cells. • In agreement, LTD 4 triggers inactivation of GSK-3β, activation of TCF/LEF and increased expression of Cyclin D1 and c-Myc. • LTD 4 also caused a significant reduction in the expression of E-cadherin and an increased migration of colon cancer cells

  14. Tritium-labelled leukotriene B4 binding to the guinea-pig spleen membrane preparation: a rich tissue source for a high-affinity leukotriene B4 receptor site

    International Nuclear Information System (INIS)

    Cheng, J.B.; Cheng, E.I.; Kohi, F.; Townley, R.G.

    1986-01-01

    Intact human granulocytes contain a leukotriene (LT) B4 receptor binding site, but the limited supply of these cells could adversely affect further progress of the study of this receptor. To select a tissue homogenate rich for this site, we have characterized the binding of highly specific [ 3 H]LTB4 to guinea-pig spleen membranes and we have determined the ability of LTB4 to compete with [ 3 H]LTB4 for binding sites in the membranes of 10 nonspleen tissues. In the spleen membrane, MgCl2 and CaCl2 enhanced [ 3 H]LTB4 binding, but NaCl and KCl decreased it. Spleen [ 3 H] LTB4 binding was a function of protein concentration and was rapid, reversible, stereoselective and saturable. Kinetic analyses showed that the rate constant for association and dissociation at 25 0 C was 0.47 nM-1 min-1 and 0.099 min-1, respectively. A Scatchard plot of the data of the equilibrium experiment resulted a straight line with a dissociation constant of 1.8 nM and a density of 274 fmol/mg of protein. Moreover, the LTB4/[ 3 H]LTB4 competition study performed at 4 or 25 0 C revealed the inhibitory constant (Ki) of LTB4 to be in the nanomolar range. The rank order of agents competing for spleen [ 3 H]LTB4 binding was: LTB4 (Ki = 2.8 nM) greater than 20-hydroxy-LTB4 (23 nM) greater than LTA4 (48 nM) greater than LTA4 methyl ester (0.13 microM) greater than 20-carboxy-LTB4 (greater than 6.6 microM) greater than or equal to arachidonic acid (0.15mM) = FPL-55,712 and FPL-57,231 (0.1-0.2 mM). Competition studies further indicated that felodipine, a 1,4-dihyropyridine Ca++ channel blocker, exhibited micromolar inhibition of spleen [ 3 H]LTB4 binding

  15. Impact of arachidonic versus eicosapentaenoic acid on exotonin-induced lung vascular leakage: relation to 4-series versus 5-series leukotriene generation.

    Science.gov (United States)

    Grimminger, F; Wahn, H; Mayer, K; Kiss, L; Walmrath, D; Seeger, W

    1997-02-01

    Escherichia coli hemolysin (HlyA) is a proteinaceous pore-forming exotoxin that is implicated as a significant pathogenicity factor in extraintestinal E. coli infections including sepsis. In perfused rabbit lungs, subcytolytic concentrations of the toxin evoke thromboxane-mediated vasoconstriction and prostanoid-independent protracted vascular permeability increase (11). In the present study, the influence of submicromolar concentrations of free arachidonic acid (AA) and eicosapentaenoic acid (EPA) on the HlyA-induced leakage response was investigated. HlyA at concentration from 0.02 to 0.06 hemolytic units/ml provoked a dose-dependent, severalfold increase in the capillary filtration coefficient (Kfc), accompanied by the release of leukotriene(LT)B4, LTC4, and LTE4 into the recirculating buffer fluid. Simultaneous application of 100 nmol/L AA markedly augmented the HlyA-elicited leakage response, concomitant with an amplification of LTB4 release and a change in the kinetics of cysteinyl-LT generation. In contrast, 50 to 200 nmol/L EPA suppressed in a dose-dependent manner the HlyA-induced increase in Kfc values. This was accompanied by a blockage of 4-series LT generation and a dose-dependent appearance of LTB5, LTC5, and LTE5. In addition, EPA fully antagonized the AA-induced amplification of the HlyA-provoked Kfc increase, again accompanied by a shift from 4-series to 5-series LT generation. We conclude that the vascular leakage provoked by HlyA in rabbit lungs is differentially influenced by free AA versus free EPA, related to the generation of 4- versus 5-series leukotrienes. The composition of lipid emulsions used for parenteral nutrition may thus influence inflammatory capillary leakage.

  16. Determination of thromboxanes, leukotrienes and lipoxins using high-temperature capillary liquid chromatography-tandem mass spectrometry and on-line sample preparation

    DEFF Research Database (Denmark)

    Dahl, Sandra Rinne; Kleiveland, Charlotte Ramstad; Kassem, Moustapha

    2009-01-01

    An on-line strong cation-exchange (SCX)-reversed-phase (RP) capillary liquid chromatographic (cLC) method with ion-trap tandem mass spectrometric (IT-MS/MS) detection for the simultaneous determination of thromboxane (TX) B(2), TXB(3), leukotriene (LT) B(4), LTD(4) and lipoxin (LX) A(4) in cell...

  17. The inflammatory mediator leukotriene D{sub 4} induces subcellular β-catenin translocation and migration of colon cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Salim, Tavga [Division of Cell and Experimental Pathology, Department of Laboratory Medicine, Lund University, Clinical Research Center, Skåne University Hospital, Malmö (Sweden); Sand-Dejmek, Janna [Division of Cell and Experimental Pathology, Department of Laboratory Medicine, Lund University, Clinical Research Center, Skåne University Hospital, Malmö (Sweden); Section of Surgery, Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö (Sweden); Bayer HealthCare, Pharmaceuticals Medical Affairs, Solna (Sweden); Sjölander, Anita, E-mail: anita.sjolander@med.lu.se [Division of Cell and Experimental Pathology, Department of Laboratory Medicine, Lund University, Clinical Research Center, Skåne University Hospital, Malmö (Sweden)

    2014-02-15

    The abnormal activation of the Wnt/β-catenin pathway frequently occurs in colorectal cancer. The nuclear translocation of β-catenin activates the transcription of target genes that promote cell proliferation, survival, and invasion. The pro-inflammatory mediator leukotriene D{sub 4} (LTD{sub 4}) exerts its effects through the CysLT{sub 1} receptor. We previously reported an upregulation of CysLT{sub 1}R in patients with colon cancer, suggesting the importance of leukotrienes in colon cancer. The aim of this study was to investigate the impact of LTD{sub 4} on Wnt/β-catenin signaling and its effects on proliferation and migration of colon cancer cells. LTD{sub 4} stimulation led to an increase in β-catenin expression, β-catenin nuclear translocation and the subsequent transcription of MYC and CCND1. Furthermore, LTD{sub 4} significantly reduced the expression of E-cadherin and β-catenin at the plasma membrane and increased the migration and proliferation of HCT116 colon cancer cells. The effects of LTD{sub 4} can be blocked by the inhibition of CysLT{sub 1}R. Furthermore, LTD{sub 4} induced the inhibition of glycogen synthase kinase 3 (GSK)-3β activity, indicating a crosstalk between the G-protein-coupled receptor CysLT{sub 1} and the Wnt/β-catenin pathway. In conclusion, LTD{sub 4}, which can be secreted from macrophages and leukocytes in the tumor microenvironment, induces β-catenin translocation and the activation of β-catenin target genes, resulting in the increased proliferation and migration of colon cancer cells. - Highlights: • Leukotriene D{sub 4} (LTD{sub 4}) lowers membrane β-catenin but increases nuclear β-catenin levels in colon cancer cells. • In agreement, LTD{sub 4} triggers inactivation of GSK-3β, activation of TCF/LEF and increased expression of Cyclin D1 and c-Myc. • LTD{sub 4} also caused a significant reduction in the expression of E-cadherin and an increased migration of colon cancer cells.

  18. Stereoselective semi-hydrogenation and deuteration of a diacetylenic precursor of leukotriene B4 methyl ester

    International Nuclear Information System (INIS)

    Pontikis, R.; Le Merrer, Y.; Depezay, J.-C.; Petillot, Y.; Rousseau, B.; Beaucourt, J.P.

    1990-01-01

    [6,7,14,15- 2 H4]-Leukotriene B4 methyl ester was prepared by reduction with deuterium gas of a suitable precursor (deuterium incorporation > 90%). Several catalytic semi-hydrogenations were affected in order to determine the best conditions for the labeling step. (author)

  19. Sesquiterpene glucosides from anti-leukotriene B4 release fraction of Taraxacum officinale.

    Science.gov (United States)

    Kashiwada, Y; Takanaka, K; Tsukada, H; Miwa, Y; Taga, T; Tanaka, S; Ikeshiro, Y

    2001-01-01

    Chemical examination of the MeOH extract of the root of Taraxacum officinale, which exhibited inhibitory activity on the formation of leukotriene B4 from activated human neutrophils, has resulted in the isolation of 14-O-beta-D-glucosyl-11,13-dihydro-taraxinic acid (1) and 14-O-beta-D-glucosyl-taraxinic acid (2). The absolute stereostructure of 1 has been established by X-ray chrystallographic examination.

  20. The cysteinyl leukotriene 2 receptor contributes to all-trans retinoic acid-induced differentiation of colon cancer cells

    International Nuclear Information System (INIS)

    Bengtsson, Astrid M; Jönsson, Gunilla; Magnusson, Cecilia; Salim, Tavga; Axelsson, Cecilia; Sjölander, Anita

    2013-01-01

    Cysteinyl leukotrienes (CysLTs) are potent pro-inflammatory mediators that are increased in samples from patients with inflammatory bowel diseases (IBDs). Individuals with IBDs have enhanced susceptibility to colon carcinogenesis. In colorectal cancer, the balance between the pro-mitogenic cysteinyl leukotriene 1 receptor (CysLT 1 R) and the differentiation-promoting cysteinyl leukotriene 2 receptor (CysLT 2 R) is lost. Further, our previous data indicate that patients with high CysLT 1 R and low CysLT 2 R expression have a poor prognosis. In this study, we examined whether the balance between CysLT 1 R and CysLT 2 R could be restored by treatment with the cancer chemopreventive agent all-trans retinoic acid (ATRA). To determine the effect of ATRA on CysLT 2 R promoter activation, mRNA level, and protein level, we performed luciferase gene reporter assays, real-time polymerase chain reactions, and Western blots in colon cancer cell lines under various conditions. ATRA treatment induces CysLT 2 R mRNA and protein expression without affecting CysLT 1 R levels. Experiments using siRNA and mutant cell lines indicate that the up-regulation is retinoic acid receptor (RAR) dependent. Interestingly, ATRA also up-regulates mRNA expression of leukotriene C 4 synthase, the enzyme responsible for the production of the ligand for CysLT 2 R. Importantly, ATRA-induced differentiation of colorectal cancer cells as shown by increased expression of MUC-2 and production of alkaline phosphatase, both of which could be reduced by a CysLT 2 R-specific inhibitor. This study identifies a novel mechanism of action for ATRA in colorectal cancer cell differentiation and demonstrates that retinoids can have anti-tumorigenic effects through their action on the cysteinyl leukotriene pathway

  1. Liquid chromatography/mass spectrometry analysis of exhaled leukotriene B4 in asthmatic children

    Directory of Open Access Journals (Sweden)

    Barnes Peter J

    2005-10-01

    Full Text Available Abstract Background The role of leukotriene (LT B4, a potent inflammatory mediator, in atopic asthmatic and atopic nonasthmatic children is largely unknown. The lack of a gold standard technique for measuring LTB4 in exhaled breath condensate (EBC has hampered its quantitative assessment in this biological fluid. We sought to measure LTB4 in EBC in atopic asthmatic children and atopic nonasthmatic children. Exhaled nitric oxide (NO was measured as an independent marker of airway inflammation. Methods Fifteen healthy children, 20 atopic nonasthmatic children, 25 steroid-naïve atopic asthmatic children, and 22 atopic asthmatic children receiving inhaled corticosteroids were studied. The study design was of cross-sectional type. Exhaled LTB4 concentrations were measured using liquid chromatography/mass spectrometry-mass spectrometry (LC/MS/MS with a triple quadrupole mass spectrometer. Exhaled NO was measured by chemiluminescence with a single breath on-line method. LTB4 values were expressed as the total amount (in pg of eicosanoid expired in the 15-minute breath test. Kruskal-Wallis test was used to compare groups. Results Compared with healthy children [87.5 (82.5–102.5 pg, median and interquartile range], exhaled LTB4 was increased in steroid-naïve atopic asthmatic [255.1 (175.0–314.7 pg, p 4 than steroid-naïve asthmatics [125.0 (25.0–245.0 pg vs 255.1 (175.0–314.7 pg, p Conclusion In contrast to exhaled NO concentrations, exhaled LTB4 values are selectively elevated in steroid-naïve atopic asthmatic children, but not in atopic nonasthmatic children. Although placebo control studies are warranted, inhaled corticosteroids seem to reduce exhaled LTB4 in asthmatic children. LC/MS/MS analysis of exhaled LTB4 might provide a non-invasive, sensitive, and quantitative method for airway inflammation assessment in asthmatic children.

  2. Stereoselective semi-hydrogenation and deuteration of a diacetylenic precursor of leukotriene B sub 4 methyl ester

    Energy Technology Data Exchange (ETDEWEB)

    Pontikis, R.; Le Merrer, Y.; Depezay, J.-C. (U.D.C. CNRS-INSERM (URA 400), 75, Paris (France). Lab. de Chimie et Biochimie Pharamacologiques et Toxicologiques); Petillot, Y.; Rousseau, B.; Beaucourt, J.P. (CEA Centre d' Etudes Nucleaires de Saclay, 91 - Gif-sur-Yvette (France). Service des Molecules Marquees)

    1990-10-01

    (6,7,14,15-{sup 2}H4)-Leukotriene B4 methyl ester was prepared by reduction with deuterium gas of a suitable precursor (deuterium incorporation > 90%). Several catalytic semi-hydrogenations were affected in order to determine the best conditions for the labeling step. (author).

  3. Cysteinyl leukotrienes C4 and D4 downregulate human mast cell expression of toll-like receptors 1 through 7.

    Science.gov (United States)

    Karpov, V; Ilarraza, R; Catalli, A; Kulka, M

    2018-01-01

    Cysteinyl leukotrienes (CysLT) are potent inflammatory lipid molecules that mediate some of the pathophysiological responses associated with asthma such as bronchoconstriction, vasodilation and increased microvascular permeability. As a result, CysLT receptor antagonists (LRA), such as montelukast, have been used to effectively treat patients with asthma. We have recently shown that mast cells are necessary modulators of innate immune responses to bacterial infection and an important component of this innate immune response may involve the production of CysLT. However, the effect of LRA on innate immune receptors, particularly on allergic effector cells, is unknown. This study determined the effect of CysLT on toll-like receptor (TLR) expression by the human mast cell line LAD2. Real-time PCR analysis determined that LTC4, LTD4 and LTE4 downregulated mRNA expression of several TLR. Specifically in human CD34+-derived human mast cells (HuMC), LTC4 inhibited expression of TLR1, 2, 4, 5, 6 and 7 while LTD4 inhibited expression of TLR1-7. Montelukast blocked LTC4-mediated downregulation of all TLR, suggesting that these effects were mediated by activation of the CysLT1 receptor (CysLT1R). Flow cytometry analysis confirmed that LTC4 downregulated surface expression of TLR2 which was blocked by montelukast. These data show that CysLT can modulate human mast cell expression of TLR and that montelukast may be beneficial for innate immune responses mediated by mast cells.

  4. Endogenous leukotriene formation during anaphylactic shock

    International Nuclear Information System (INIS)

    Keppler, A.; Oerning, L.; Bernstroem, K.; Hammarstroem, S.

    1987-01-01

    Leukotriene (LT)C 4 is a biologically active substance, presumed to play major roles as a mediator of allergic and anaphylactic reactions. It is formed e.g. by basophilic and eosinophilic leukocytes, monocytes, macrophages, and mast cells. In cells having IgE receptors, bridging of these by divalent anti-IgE-receptor antibodies or by interaction between receptor-bound IgE and anti-IgE will induce LTC 4 formation. Leukotriene formation has also been demonstrated in other in vitro models of immediate hypersensivity. The biological actions of LTC 4 , comprise induction of airway obstruction, constriction of coronary arteries, hypotension, and plasma extravasation. Leukotriene formation in vivo may mediate anaphylactic shock symptoms and cause the death of an animal. In order to prove the presumed mediator role of this substance in anaphylactic reactions, it is necessary to demonstrate its endogenous formation during shock. Studies on the metabolism of LTC 4 have revealed rapid catabolism by various transformations of the peptide substituent. Recently, three metabolites were demonstrated to be excreted as end-products in man (LTE 4 ,) and the rat (N-acetyl LTE 4 and N-acetyl 11-trans LTE 4 ). By monitoring biliary N-acetyl LTE 4 levels, endogenous leukotriene formation in the rat was demonstrated in vivo after tissue trauma and endotoxin shock. We now wish to report evidence for endogenous leukotriene C 4 production during anaphylactic shock in guinea pigs. 37 refs. (author)

  5. Leukotriene B4leukotriene B4 receptor axis promotes oxazolone-induced contact dermatitis by directing skin homing of neutrophils and CD8+ T cells

    Science.gov (United States)

    Lv, Jiaoyan; Zou, Linlin; Zhao, Lina; Yang, Wei; Xiong, Yingluo; Li, Bingji; He, Rui

    2015-01-01

    Leukotriene B4 (LTB4) is a lipid mediator that is rapidly generated in inflammatory sites, and its functional receptor, BLT1, is mostly expressed on immune cells. Contact dermatitis is a common inflammatory skin disease characterized by skin oedema and abundant inflammatory infiltrates, primarily including neutrophils and CD8+ T cells. The role of the LTB4–BLT1 axis in contact dermatitis remains largely unknown. In this study, we found up-regulated gene expression of 5-lipoxygenase and leukotriene A4 hydrolase, two critical enzymes for LTB4 synthesis, BLT1 and elevated LTB4 levels in skin lesions of oxazolone (OXA)-induced contact dermatitis. BLT1 deficiency or blockade of LTB4 and BLT1 by the antagonists, bestatin and U-75302, respectively, in the elicitation phase caused significant decreases in ear swelling and skin-infiltrating neutrophils and CD8+ T cells, which was accompanied by significantly reduced skin expression of CXCL1, CXCL2, interferon-γ and interleukin-1β. Furthermore, neutrophil depletion during the elicitation phase of OXA-induced contact dermatitis also caused significant decreases in ear swelling and CD8+ T-cell infiltration accompanied by significantly decreased LTB4 synthesis and gene expression of CXCL2, interferon-γ and interleukin-1β. Importantly, subcutaneous injection of exogenous LTB4 restored the skin infiltration of CD8+ T cells in neutrophil-depleted mice following OXA challenge. Collectively, our results demonstrate that the LTB4–BLT1 axis contributes to OXA-induced contact dermatitis by mediating skin recruitment of neutrophils, which are a major source of LTB4 that sequentially direct CD8+ T-cell homing to OXA-challenged skin. Hence, LTB4 and BLT1 could be potential therapeutic targets for the treatment of contact dermatitis. PMID:25959240

  6. SRS-A leukotrienes decrease the activity of human respiratory cilia

    DEFF Research Database (Denmark)

    Bisgaard, H; Pedersen, M

    1987-01-01

    We have studied the effects of the slow reacting substance of anaphylaxis (SRS-A) constituents leukotrienes (LT) C4 and D4 on the ciliary activity of human respiratory cells. The ciliary beat frequency on human nasal cells harvested by cell scraping from the inferior turbinate was measured...

  7. The Role of PPAR Receptors and Leukotriene B4 Receptors in Mediating the Effects of LY293111 in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Thomas E. Adrian

    2008-01-01

    Full Text Available Pancreatic cancer is a devastating disease in which current therapies are inadequate. Separate lines of research have identified the 5-lipoxygenase/leukotriene B4 receptor pathway and the PPAR pathway as potential targets for prevention or treatment of this disease. LY293111 was originally designed as a potent leukotriene B4 receptor antagonist for treatment of inflammatory conditions. LY293111 was also known to have inhibitory effects on 5-lipoxygenase, which is upstream of the production of leukotrienes. LY293111 was shown to have potent anticancer effects in pancreatic cancer and several other solid malignancies, where it caused cell cycle arrest and marked apoptosis. Subsequently, it came to light that LY293111 exhibited PPAR agonist activity in addition to its effects on the 5-lipoxygenase pathway. This raises the question of which of the two targets is of greatest importance with regard to the anticancer effects of this agent. The evidence to date is not conclusive, but suggests that the effects of LY293111 may be mediated by both LTB4 receptors and PPAR.

  8. Release of leukotriene C4 from human polymorphonuclear leucocytes as determined by radioimmunoassay

    International Nuclear Information System (INIS)

    Aehringhaus, U.; Woelbling, R.H.; Peskar, B.M.; Peskar, B.A.; Koenig, W.; Patrono, C.

    1982-01-01

    Rabbits were immunized with a conjugate of leukotriene (LT)C 4 and bovine serum albumin prepared by coupling the single free amino group of the hapten to the protein using gluteraldehyde. Binding of [ 3 H]LTC 4 to the antibodies obtained is inhibited by 50% with 1.5 ng LTC 4 . The relative cross-section of LTD 4 is 16% and of LTC 4 -methyl ester 3.6%. The validity of the radioimmunoassay was demonstrated by comparison with bioassay using the isolated guinea pig ileum. Using the radioimmunoassay it could be shown that endogenous LTC 4 is released in a dose-dependent manner by human polymorphonuclear leucocytes stimulated with the divalent cation ionophore A23187. (Auth.)

  9. Identification of a murine cysteinyl leukotriene receptor by expression in Xenopus laevis oocytes

    DEFF Research Database (Denmark)

    Mollerup, Jens; Jørgensen, Sune T.; Hougaard, Charlotte

    2001-01-01

    We report the identification of an EST encoding a murine cysteinyl leukotriene (mCysLT) receptor. LTD4, LTC4 and LTE4 but not LTB4 or various nucleotides activated Ca2+-evoked Cl- currents in mCysLT1 expressing Xenopus laevis oocytes. The response to LTD4 was blocked by MK-571, reduced by pretrea...... by pretreatment with pertussis toxin (PTX), and was partly dependent on extracellular Ca2+. The identified murine CysLT1 receptor differs from the hCysLT1 receptor with regard to PTX sensitivity, receptor-mediated Ca2+ influx, and antagonist sensitivity....

  10. Cysteinyl leukotriene signaling aggravates myocardial hypoxia in experimental atherosclerotic heart disease

    DEFF Research Database (Denmark)

    Nobili, Elena; Salvado, M Dolores; Folkersen, Lasse Westergaard

    2012-01-01

    Cysteinyl-leukotrienes (cys-LT) are powerful spasmogenic and immune modulating lipid mediators involved in inflammatory diseases, in particular asthma. Here, we investigated whether cys-LT signaling, in the context of atherosclerotic heart disease, compromises the myocardial microcirculation and ...

  11. Bronchial effects of leukotriene D4 inhalation in normal human lung

    DEFF Research Database (Denmark)

    Bisgaard, H; Groth, S

    1987-01-01

    airways in asthmatic patients out of attack. LTD4 caused a dose-dependent obstruction of the airways as measured by partial flow-volume curves and volume of trapped gas, yet only minor changes in forced expiratory volume in 1 s (FEV1) and peak expiratory flow rate. LTD4 was 1900-7000 times more potent......The aim of the study was to investigate whether inhaled leukotriene (LT) D4 could mimic the characteristics of asthmatic patients after allergen-induced attack, i.e. a prolonged subclinical bronchial obstruction, an increased reactivity of the airways and a late reaction. The effects of LTD4 were...... than histamine. LTD4 inhalations were almost symptomless as opposed to the irritative and dyspnoeic symptoms seen after inhalation of histamine. The time duration for the induced change in partial flow-volume curves was the same for the two drugs. Approximately 30 min elapsed until the bronchial...

  12. COMPARISON OF SELECTIVE AND NON SELECTIVE CYCLO-OXYGENASE 2 INHIBITORS IN EXPERIMENTAL COLITIS EXACERBATION: role of leukotriene B4 and superoxide dismutase

    Directory of Open Access Journals (Sweden)

    José Wander BREGANÓ

    2014-09-01

    Full Text Available Context Nonsteroidal anti-inflammatory drugs are considered one of the most important causes of reactivation of inflammatory bowel disease. With regard to selective cyclo-oxygenase 2 inhibitors, the results are controversial in experimental colitis as well as in human studies. Objectives The aim this study is to compare nonsteroidal anti-inflammatory drugs effects, selective and non selective cyclo-oxygenase 2 inhibitors, in experimental colitis and contribute to the understanding of the mechanisms which nonsteroidal anti-inflammatory drugs provoke colitis exacerbation. Methods Six groups of rats: without colitis, with colitis, and colitis treated with celecoxib, ketoprofen, indometacin or diclofenac. Survival rates, hemoglobin, plasmatic albumin, colonic tissue of interleukin-1ß, interleukin-6, tumor necrosis factor alpha, prostaglandin E2, catalase, superoxide dismutase, thiobarbituric acid-reactive substances, chemiluminescence induced by tert-butil hydroperoxides, and tissue and plasmatic leukotriene B4 were determined. Results The groups treated with diclofenac or indometacin presented lower survival rates, hemoglobin and albumin, higher tissue and plasmatic leukotriene B4 and tissue superoxide dismutase than the group treated with celecoxib. Ketoprofen presented an intermediary behavior between diclofenac/indometacin and celecoxib, concerning to survival rate and albumin. The groups without colitis, with colitis and with colitis treated with celecoxib showed leukotriene B4 and superoxide dismutase lower levels than the groups treated with nonselective cyclo-oxygenase 2 inhibitors. Conclusions Diclofenac and indometacin presented the highest degree of induced colitis exacerbation with nonsteroidal anti-inflammatory drugs, celecoxib did not show colitis exacerbation, and ketoprofen presented an intermediary behavior between diclofenac/indometacin and celecoxib. These results suggest that leukotriene B4 and superoxide dismutase can be

  13. Endogenous leukotriene D4 formation during anaphylactic shock in the guinea pig

    International Nuclear Information System (INIS)

    Keppler, A.; Oerning, L.; Bernstroem, K.; Hammarstroem, S.

    1987-01-01

    Experiments on the metabolism and excretion of i.v. administered selectively labeled [ 3 H 8 ]leukotriene C 4 in bile duct-cannulated guinea pigs indicated predominantly biliary excretion of tritium. The major leukotriene metabolite in bile was identified as leukotriene D 4 . By monitoring leukotriene excretion radioimmunochromatographically, it was shown that guinea pigs suffering from anaphylactic shock produce leukotriene D 4 endogenously. Immunological challenge of animals sensitized to ovalbumin was accompanied by an increase of biliary leukotriene D 4 concentrations from 10 +/- 1 to 86 +/- 10 nM. When considering that bile flow was decreased to about half after challenge, the excretion rate of leukotriene D 4 in bile increased from 0.88 +/- 0.16 before 3.18 +/- 0.38 pmol x min -1 x kg -1 after challenge. It is concluded that systemic anaphylaxis in the guinea pig is associated with endogenous generation of leukotriene C 4

  14. A radiochemical assay for detection of leukotriene B4 production from isolated cells

    International Nuclear Information System (INIS)

    Aharony, D.; Dobson, P.; Krell, R.D.

    1984-01-01

    A radiochemical procedure for quantitating the effect of inhibitors of leukotriene B4 (LTB4) biosynthesis is described. Rat peritoneal cells were labeled with 3 H-arachidonic acid and stimulated with the calcium ionophore A23187. 3 H-LTB4 was isolated by processing on C18-Sep Pak cartridges followed by reverse-phase high pressure liquid chromatography (HPLC). The identity of this product, as well as other arachidonic acid metabolites, was verified by using silicic acid column chromatography followed by straight-phase HPLC and thin layer chromatography. Using this assay, LTB4 release by ionophore A23187 has been shown to be both time- and concentration-dependent. Indomethacin enhanced, while NDGA and ETYA inhibited, the A23187-induced production of LTB4. This procedure is both simple and direct and is capable of assessing the ability of novel compounds to alter LTB4 production

  15. Upregulation of Leukotriene Receptors in Gastric Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Venerito, Marino [Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Leipziger Str. 44, Magdeburg 39120 (Germany); Kuester, Doerthe [Institute of Pathology, Otto-von-Guericke University, Leipziger Str. 44, Magdeburg 39120 (Germany); Harms, Caroline [Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Leipziger Str. 44, Magdeburg 39120 (Germany); Schubert, Daniel [Department of General, Visceral and Vascular Surgery, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, Magdeburg 39120 (Germany); Wex, Thomas, E-mail: thomas.wex@med.ovgu.de; Malfertheiner, Peter [Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Leipziger Str. 44, Magdeburg 39120 (Germany)

    2011-08-08

    Leukotrienes (LT) mediate allergic and inflammatory processes. Previously, we identified significant changes in the expression pattern of LT receptors in the gastric mucosa after eradication of Helicobacter pylori infection. The aim of the present study was to evaluate the expression of 5-lipoxygenase (5-LOX) and LT receptors in gastric cancer (GC). The expression of 5-LOX and receptors for LTB4 (BLT-1, BLT-2) and cysteinyl-LT (CysLT-1, CysLT-2) were analyzed by immunohistochemistry (IHC) in GC samples of 35 consecutive patients who underwent gastrectomy and in 29 tumor-free tissue specimens from gastric mucosa. Male-to-female ratio was 24:11. The median age was 70 years (range 34–91). Twenty-two patients had GC of intestinal, six of diffuse, six of mixed and one of undifferentiated type. The IHC analysis showed a nearly ubiquitous expression of studied proteins in GC (88–97%) and in tumor-free specimens as well (89–100%). An increase in the immunoreactive score of both BLT receptors and CysLT-1 was observed in GC compared to tumor-free gastric mucosa (p < 0.001 for BLT-1; p < 0.01 for BLT-2 and CysLT-1, Mann-Whitney U-test). No differences in the IHC expression of 5-LOX and CsyLT-2 were observed between GC and tumor-free mucosa. The expression of BLT-2, CysLT-1 and CysLT-2 was increased in GC of intestinal type when compared to the diffuse type (p < 0.05; Mann-Whitney U-test). LTB4 receptors and CysLT-1 are up-regulated in GC tissue implying a role in gastric carcinogenesis.

  16. Development of a model system to study leukotriene-induced modification of radiation sensitivity in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Walden, Jr, T L; Holahan, Jr, E V; Catravas, G N

    1986-01-01

    Leukotrienes (LT) are an important class of biological mediators for which no information exists concerning their synthesis following a radiation insult or on their ability to modify cellular response to a subsequent radiation exposure. Results are presented which illustrate that the Chinese hamster lung fibroblast cell line, V79A03, is useful as a model system to study the metabolic fate of leukotrienes and the effect of LT on radiation sensitivity of mammalian cells in vitro. (U.K.).

  17. Cysteinyl leukotriene E4 activates human group 2 innate lymphoid cells and enhances the effect of prostaglandin D2 and epithelial cytokines.

    Science.gov (United States)

    Salimi, Maryam; Stöger, Linda; Liu, Wei; Go, Simei; Pavord, Ian; Klenerman, Paul; Ogg, Graham; Xue, Luzheng

    2017-10-01

    Group 2 innate lymphoid cells (ILC2s) are a potential innate source of type 2 cytokines in the pathogenesis of allergic conditions. Epithelial cytokines (IL-33, IL-25, and thymic stromal lymphopoietin [TSLP]) and mast cell mediators (prostaglandin D 2 [PGD 2 ]) are critical activators of ILC2s. Cysteinyl leukotrienes (cysLTs), including leukotriene (LT) C 4 , LTD 4 , and LTE 4 , are metabolites of arachidonic acid and mediate inflammatory responses. Their role in human ILC2s is still poorly understood. We sought to determine the role of cysLTs and their relationship with other ILC2 stimulators in the activation of human ILC2s. For ex vivo studies, fresh blood from patients with atopic dermatitis and healthy control subjects was analyzed with flow cytometry. For in vitro studies, ILC2s were isolated and cultured. The effects of cysLTs, PGD 2 , IL-33, IL-25, TSLP, and IL-2 alone or in combination on ILC2s were defined by using chemotaxis, apoptosis, ELISA, Luminex, quantitative RT-PCR, and flow cytometric assays. The effect of endogenous cysLTs was assessed by using human mast cell supernatants. Human ILC2s expressed the LT receptor CysLT 1 , levels of which were increased in atopic subjects. CysLTs, particularly LTE 4 , induced migration, reduced apoptosis, and promoted cytokine production in human ILC2s in vitro. LTE 4 enhanced the effect of PGD 2 , IL-25, IL-33, and TSLP, resulting in increased production of type 2 and other proinflammatory cytokines. The effect of LTE 4 was inhibited by montelukast, a CysLT 1 antagonist. Interestingly, addition of IL-2 to LTE 4 and epithelial cytokines significantly amplified ILC2 activation and upregulated expression of the receptors for IL-33 and IL-25. CysLTs, particularly LTE 4 , are important contributors to the triggering of human ILC2s in inflammatory responses, particularly when combined with other ILC2 activators. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Omega-oxidation is the major pathway for the catabolism of leukotriene B4 in human polymorphonuclear leukocytes.

    Science.gov (United States)

    Shak, S; Goldstein, I M

    1984-08-25

    Leukotriene B4 (LTB4), formed by the 5-lipoxygenase pathway in human polymorphonuclear leukocytes (PMN), may be an important mediator of inflammation. Recent studies suggest that human leukocytes can convert LTB4 to products that are less biologically active. To examine the catabolism of LTB4, we developed (using high performance liquid chromatography) a sensitive, reproducible assay for this mediator and its omega-oxidation products (20-OH- and 20-COOH-LTB4). With this assay, we have found that human PMN (but not human monocytes, lymphocytes, or platelets) convert exogenous LTB4 almost exclusively to 20-OH- and 20-COOH-LTB4 (identified by gas chromatography-mass spectrometry). Catabolism of exogenous LTB4 by omega-oxidation is rapid (t1/2 approximately 4 min at 37 degrees C in reaction mixtures containing 1.0 microM LTB4 and 20 X 10(6) PMN/ml), temperature-dependent (negligible at 0 degrees C), and varies with cell number as well as with initial substrate concentration. The pathway for omega-oxidation in PMN is specific for LTB4 and 5(S),12(S)-dihydroxy-6,8,10,14-eicosatetraenoic acid (only small amounts of other dihydroxylated-derivatives of arachidonic acid are converted to omega-oxidation products). Even PMN that are stimulated by phorbol myristate acetate to produce large amounts of superoxide anion radicals catabolize exogenous leukotriene B4 primarily by omega-oxidation. Finally, LTB4 that is generated when PMN are stimulated with the calcium ionophore, A23187, is rapidly catabolized by omega-oxidation. Thus, human PMN not only generate and respond to LTB4, but also rapidly and specifically catabolize this mediator by omega-oxidation.

  19. Low expression of CysLT1R and high expression of CysLT2R mediate good prognosis in colorectal cancer

    DEFF Research Database (Denmark)

    Magnusson, Cecilia; Mezhybovska, Maryna; Lörinc, Ester

    2010-01-01

    Colorectal cancer is the third most common cancer type in the Western world. In search of new treatment possibilities, the inflammation mediators, know as cysteinyl leukotrienes (CysLTs), have been shown to regulate intestinal epithelial cell survival and proliferation via the CysLT(1)R, and cell...... microarray of 329 colorectal patients. We found that high nuclear expression of CysLT(1)R is associated with a poor prognosis, whereas high nuclear expression of CysLT(2)R is associated with a good prognosis. We also observed that patients with colorectal tumours characterised by high CysLT(1)R but low Cys...

  20. Leukotriene formation by purified 5-lipoxygenase from rat basophilic leukemia cells

    International Nuclear Information System (INIS)

    Hogaboom, G.K.; Cook, M.; Sarau, H.M.; Newton, J.F.; Crooke, S.T.

    1986-01-01

    Arachidonate 5-lipoxygenase (5-LO) from rat basophilic leukemia (RBL-1) cell high speed (105,000 x g for 60 min) supernatants was purified to electrophoretic homogeneity by gel filtration and anion-exchange protein-high pressure liquid chromatography (HPLC). The 5-LO rapidly converted [ 14 C]arachidonate at 20 0 C to [ 14 C]5-hydroperoxyeicosate-traenoic acid (HPETE) as determined by reversed phase-HPLC, scanning spectrophotometry and radiochemical detection. In addition, 5-LO converted both 5-HPETE and arachidonate to 5,12-dihydroxyeicosatetraenoic acids (diHETEs). The 5,12-diHETEs were identified as 6-trans-leukotriene (LT) B4 and 6-trans-12-epi-LTB4 as determined by reversed phase HPLC, scanning spectrophotometry and gas chromatography-mass spectrometry. These data indicate that the RBL-1 5-LO and LTA4 synthetase activities reside on the same protein and that it catalyzes the bioconversion of arachidonate to not only 5-HPETE but also to LTA4. The results suggest that a critical regulatory step in LT biosynthesis in mammalian systems involves the intricate coupling of the enzymes 5-LO and LTA4 synthetase and the interactions of their respective cofactors, substrates and reaction products

  1. Is there a role for leukotrienes as mediators of ethanol-induced gastric mucosal damage?

    International Nuclear Information System (INIS)

    Wallace, J.L.; Beck, P.L.; Morris, G.P.

    1988-01-01

    The role of leukotriene (LT) C 4 as a mediator of ethanol-induced gastric mucosal damage was investigated. Rats were pretreated with a number of compounds, including inhibitors of leukotriene biosynthesis and agents that have previously been shown to reduce ethanol-induced damage prior to oral administration of absolute ethanol. Ethanol administration resulted in a fourfold increase in LTC 4 synthesis. LTC 4 synthesis could be reduced significantly by pretreatment with L651,392 or dexamethosone without altering the susceptibility of the gastric mucosa to ethanol-induced damage. Furthermore, changes in LBT 4 synthesis paralleled the changes in LTC 4 synthesis observed after ethanol administration. The effects of ethanol on gastric eicosanoid synthesis were further examined using an ex vivo gastric chamber preparation that allowed for application of ethanol to only one side of the stomach. These studies confirm that ethanol can stimulate gastric leukotriene synthesis independent of the production of hemorrhagic damage. Inhibition of LTC 4 synthesis does not confer protection to the mucosa, suggesting that LTC 4 does not play an important role in the etiology of ethanol-induced gastric damage

  2. Pharmacological modulation of human platelet leukotriene C4-synthase.

    Science.gov (United States)

    Sala, A; Folco, G; Henson, P M; Murphy, R C

    1997-03-21

    The aim of this study was to test if human platelet leukotriene C4-synthase (LTC4-S) is pharmacologically different from cloned and expressed LTC4-S and, in light of the significant homologies between 5-lipoxygenase activating protein (FLAP) and LTC4-S, if different potencies of leukotriene synthesis inhibitors acting through binding with FLAP (FLAP inhibitors) reflect in different potencies as LTC4-S inhibitors. Leukotriene C4 (LTC4) synthesis by washed human platelets supplemented with synthetic leukotriene A4 (LTA4) was studied in the absence and presence of two different, structurally unrelated FLAP inhibitors (MK-886 and BAY-X1005) as well as a direct 5-lipoxygenase inhibitor (zileuton). LTC4 production was analyzed by RP-HPLC coupled to diode array detection. We report that human platelet LTC4-S was inhibited by MK-886 and BAY-X1005 (IC50 of 4.7 microM and 91.2 microM, respectively), but not by zileuton (inactive up to 300 microM); all 3 compounds were able to inhibit 5-lipoxygenase metabolite biosynthesis in intact human polymorphonuclear leukocytes (IC50 of 0.044 microM, 0.85 microM, and 1.5 microM, respectively). Platelet LTC4-S does not appear pharmacologically different from expression cloned LTC4-S. LTC4-S inhibition by FLAP inhibitors is in agreement with the significant homology reported for expression-cloned LTC4-S with FLAP, Furthermore, functional homology of the binding sites for inhibitors on LTC4-S and FLAP is suggested by the conservation of the relative potencies of MK-886 and BAY-X1005 vs FLAP-dependent 5-lipoxygenase activity and LTC4-S inhibition: MK-886 was 19.3-fold more potent than BAY-X1005 as FLAP inhibitor and 19.6-fold more potent than BAY-X1005 as LTC4-S inhibitor.

  3. Leukotrienes B4, C4, D4 and E4 in the Exhaled Breath Condensate (EBC), Blood and Urine in Patients with Pneumoconiosis

    Czech Academy of Sciences Publication Activity Database

    Pelclová, D.; Fenclová, Z.; Vlčková, Š.; Lebedová, J.; Syslová, K.; Pecha, O.; Běláček, J.; Navrátil, Tomáš; Kuzma, Marek; Kačer, P.

    2012-01-01

    Roč. 50, č. 4 (2012), s. 299-306 ISSN 0019-8366 Institutional support: RVO:61388955 ; RVO:61388971 Keywords : leukotrienes * Lung fibrosis * exhaled breath condensate Subject RIV: CG - Electrochemistry Impact factor: 0.870, year: 2012

  4. Expression of cysLT1 and cysLT2 Receptor in Chronic Hyperplastic Eosinophilic Sinusitis

    International Nuclear Information System (INIS)

    Ouyang, Yuhui; Kamijo, Atsushi; Murata, Shin-ichi; Okamoto, Atsushi; Endo, Shuichiro; Katoh, Ryohei; Masuyama, Keisuke

    2009-01-01

    Elevated production of cysteinyl leukotrienes (cysLTs) from sinus tissues and abundant sinus eosinophils are characteristic features of chronic hyperplastic eosinophilic sinusitis (CHS). CysLTs exert their action through G-protein-coupled receptors named cysLTs receptor type I (cysLT1R) and type II (cysLT2R). These expressions of cysLT receptors in the sinus mucosa have yet to be clarified and the relationship between eosinophilia and the expression of these receptors remains obscure. We compared the expressions of cysLT1R and cysLT2R in the sinus mucosa in patients with CHS, non-eosinophilic chronic sinusitis (NECS), and control sinus tissues; and analyzed the correlation between the expression of CysLTRs and the presence of sinus eosinophils by immunohistochemistry and real-time PCR. A significantly higher percentage of eosinophils expressing cysLT2R protein was observed in patients with CHS compared with NECS and controls. In addition, cysLT2R mRNA expression in CHS was significantly higher than in NECS and controls. Furthermore, a positive correlation was observed between cysLT2R mRNA expression and the number of infiltrated eosinophils. In contrast, the cysLT1R mRNA expression did not differ significantly among these groups. The effect of cysLTs on sinus eosinophils may be mediated through the cysLT2R in patients with CHS. These results may suggest the therapeutic benefit of cysLT2R antagonists in CHS

  5. A study of the photodegradation of leukotriene B4 by ultraviolet irradiation (UVB, UVA)

    International Nuclear Information System (INIS)

    Millar, B.; Green, C.; Ferguson, J.; Raffle, E.J.; Macleod, T.M.

    1989-01-01

    In view of the presence of the polymorphonuclear leukocyte (PMN) chemoattractant Leukotriene B 4 (LTB 4 ) in surface scale of the psoriatic lesion and the known therapeutic effect of phototherapy in psoriasis, the photostability of LTB 4 was investigated. LTB 4 was irradiated with UVB (290-320 nm) from 100-1500 mJ cm -2 and UVA (320-400 nm) from 5-40 J cm -2 . Topical application of UVB irradiated LTB 4 to forearm skin of normal volunteers showed marked reduction in cutaneous erythema, paralleled by reduced transepidermal PMN migration compared with sites of application of unirradiated and UVA irradiated LTB 4 . High performance liquid chromatography (HPLC) demonstrated a dose-dependent photodegradation of LTB 4 by UVB irradiation. UVA irradiation produced no such effect. The wavelengths responsible lie within the absorption spectrum of LTB 4 . In vitro chemotaxis studies, using an under agarose technique, showed a statistically significant reduction in the migration of PMN from psoriatic and non-psoriatic subjects to the UVB irradiated LTB 4 compared with unirradiated LTB 4 , whilst UVA irradiated LTB 4 produced a normal PMN chemotactic response. (author)

  6. Combination L-T3 and L-T4 therapy for hypothyroidism.

    Science.gov (United States)

    Wartofsky, Leonard

    2013-10-01

    Because of the longstanding controversy regarding whether hypothyroid patients can be optimally replaced by treatment with levothyroxine (L-T4) alone, numerous studies have addressed potential benefits of combined therapy of triiodothyronine (T3) with L-T4. Results of these studies have failed to support a potential benefit of combined therapy. A strong argument for the addition of L-T3 to L-T4 monotherapy has been lacking until recent genetic studies indicated a rationale for such therapy among a small fraction of the hypothyroid patient population. Interest in this issue has focused on the importance of the deiodinases in maintaining the euthyroid state and the role of genetic polymorphisms in the deiodinase genes that would affect thyroid hormone concentrations in both blood and tissues. One such polymorphism in the D2 gene, Thr92Ala, is associated with reduced T4 to T3 activation in skeletal muscle and thyroid, linked to obesity and alterations in thyroid-pituitary feedback, and in responses to thyroid hormone treatment. Although our professional organizations continue to recommend L-T4 alone for the treatment of hypothyroidism, the possibility of a D2 gene polymorphism should be considered in patients on L-T4 monotherapy who continue to complain of fatigue in spite of dosage achieving low normal serum thyroid stimulating hormone levels. A suggestive clue to the presence of this polymorphism could be a higher than normal free T4/free T3 ratio. Clinicians could consider adding T3 as a therapeutic trial in selected patients. Future well controlled clinical trials will be required to more fully resolve the controversy.

  7. Leukotriene B4-Neutrophil Elastase Axis Drives Neutrophil Reverse Transendothelial Cell Migration In Vivo.

    Science.gov (United States)

    Colom, Bartomeu; Bodkin, Jennifer V; Beyrau, Martina; Woodfin, Abigail; Ody, Christiane; Rourke, Claire; Chavakis, Triantafyllos; Brohi, Karim; Imhof, Beat A; Nourshargh, Sussan

    2015-06-16

    Breaching endothelial cells (ECs) is a decisive step in the migration of leukocytes from the vascular lumen to the extravascular tissue, but fundamental aspects of this response remain largely unknown. We have previously shown that neutrophils can exhibit abluminal-to-luminal migration through EC junctions within mouse cremasteric venules and that this response is elicited following reduced expression and/or functionality of the EC junctional adhesion molecule-C (JAM-C). Here we demonstrate that the lipid chemoattractant leukotriene B4 (LTB4) was efficacious at causing loss of venular JAM-C and promoting neutrophil reverse transendothelial cell migration (rTEM) in vivo. Local proteolytic cleavage of EC JAM-C by neutrophil elastase (NE) drove this cascade of events as supported by presentation of NE to JAM-C via the neutrophil adhesion molecule Mac-1. The results identify local LTB4-NE axis as a promoter of neutrophil rTEM and provide evidence that this pathway can propagate a local sterile inflammatory response to become systemic. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Leukotrienes and leukotriene modifiers in pediatric allergic diseases

    African Journals Online (AJOL)

    Ehab

    ... 12(1):3-12. 3. Leukotrienes and leukotriene modifiers in pediatric allergic diseases ... childhood allergic diseases. This review ... produce cysteinyl-LTs and LTB4 spontaneously in vitro.8. Although nonleukocyte cells generally do not have sufficient 5-LO and FLAP to synthesize .... uninterrupted sleep in these patients.55.

  9. Elevated Plasma Level of Leukotrienes in Bronchial Asthma Patients: A Possible Clinical Relevance

    Directory of Open Access Journals (Sweden)

    Mahmoud Mansour

    1994-01-01

    Full Text Available Plasma from bronchial asthma patients and healthy controls was investigated for the content of lipoxygenase products. After lipid extraction using SEP-PAK C18 Cartridges, the lipoxygenase products were measured by Enzyme-Immunoassay. Elevated chemotactic B4 was found in plasma from asthmatic patients with mean value (483±75 pmoUL, while the mean value in normal healthy donors was (140± 12.1 pmol/L (M±SE. The levels of spasmogenic cysteinyl containing leukotrienes were also very high in the bronchial asthma patients. Elevations of leukotriene B4 and cysteinyl containing leukotrienes were detected during attacks of bronchial asthma. These results suggest that leukotriene B4 may be important in the pathogenesis of bronchial asthma and confirmed that peptidoleukotrienes playa role as chemical mediators during the asthmatic attack.

  10. Role of leukotrienes in asthma pathophysiology

    DEFF Research Database (Denmark)

    Bisgaard, H

    2000-01-01

    Inflammation is an essential component of asthma pathophysiology. While beta(2)-agonists are often used for short-term relief of acute bronchospasm, anti-inflammatory agents are required for the long-term management of chronic inflammation in this disease. Corticosteroids have emerged as the first......-line anti-inflammatory therapy for asthma management. However, in some patients, especially children, the high doses of corticosteroids that may be required to control features of hyperresponsiveness, including exercise-induced asthma, raise safety concerns. Thus, there is a need for complementary anti......-inflammatory, steroid-sparing agents in asthma therapy. Several inflammatory mediators have been targeted in an attempt to thwart this inflammatory process, but so far with little success. The cysteinyl leukotrienes (CysLT), LTC(4), LTD(4), and LTE(4), have been shown to be essential mediators in asthma, making them...

  11. Increase in salivary cysteinyl-leukotriene concentration in patients with aspirin-intolerant asthma.

    Science.gov (United States)

    Ono, Emiko; Taniguchi, Masami; Higashi, Noritaka; Mita, Haruhisa; Yamaguchi, Hiromichi; Tatsuno, Sayaka; Fukutomi, Yuma; Tanimoto, Hidenori; Sekiya, Kiyoshi; Oshikata, Chiyako; Tsuburai, Takahiro; Tsurikisawa, Naomi; Otomo, Mamoru; Maeda, Yuji; Hasegawa, Maki; Miyazaki, Eishi; Kumamoto, Toshihide; Akiyama, Kazuo

    2011-03-01

    Cysteinyl-leukotrienes (CysLTs; LTC4, LTD4, and LTE4) play a considerable role in the pathophysiology of aspirin-intolerant asthma (AIA). Saliva has recently been validated as novel, simple, and noninvasive method for investigating inflammation in patients with asthma. The aim of this study is to clarify the molecular species of CysLT in saliva and to evaluate the CysLT and LTB4 concentrations in saliva in AIA patients. We also examined how the CysLT concentration in saliva reflects that of their corresponding urinary metabolite. We preformed an analytical cross-sectional study. CysLT and LTB4 concentrations in saliva were quantified by enzyme immunoassay (EIA) following purification by high-performance liquid chromatography (HPLC). 1. When analyzed by EIA in combination with HPLC, saliva was found to consist of LTC4, LTD4 and LTE4 in similar amounts. 2. In saliva analysis among the three groups (AIA patients, aspirin-tolerant asthma [ATA] patients, and healthy subjects), both the concentrations of CysLTs and LTB4 were significantly higher in AIA patients than in ATA patients and healthy subjects. 3. We found significant correlations between CysLT concentration and LTB4 concentration in saliva in each group. 4. No significant correlation was found between the concentration of LTE4 in urine and that of CysLTs in saliva. In this study, we found higher concentrations of CysLTs and LTB4 in saliva from AIA patients than in saliva from ATA patients, suggesting that the quantification of CysLT and LTB4 concentrations in saliva may be another diagnostic strategy for AIA.

  12. Cold injury, blood-brain barrier changes, and leukotriene synthesis: Inhibition by phenidone

    International Nuclear Information System (INIS)

    Robichaud, L.J.; Marcoux, F.W.

    1990-01-01

    Transcranial cold injury in rats and guinea pigs induced cerebral extravasation of albumin labeled with Evans blue dye or 125 I, respective indicators of the area and amount of blood-brain barrier (BBB) disruption. Radioimmunoassay of brain extracts showed that cold injury induced leukotriene (LT)C4 in rat and guinea pig brains 15 min after injury. In guinea pigs, the LT synthesis inhibitor phenidone (30 mg/kg, i.p.) completely blocked cold-induced LTC4 in brain. Phenidone (30 and 100 mg/kg) also inhibited cerebral tissue accumulation of 125 I-albumin and dye in rats and guinea pigs. Phenidone is reported to show antioxidant properties and selective lipoxygenase inhibition of arachidonic acid metabolism compared to cyclooxygenase inhibitors, meclofenamate sodium, and other nonsteroidal anti-inflammatory agents. Since several oxygen and hydroxyl radical scavengers and the cyclooxygenase inhibitor, meclofenamate sodium, did not inhibit protein extravasation, the findings support a role for LT as a mediator of cold-induced changes in BBB permeability in rats and guinea pigs and suggest that the inhibitory effects of phenidone on BBB permeability may be due to inhibition of LT production

  13. Leukotriene B4-Neutrophil Elastase Axis Drives Neutrophil Reverse Transendothelial Cell Migration In Vivo

    Science.gov (United States)

    Colom, Bartomeu; Bodkin, Jennifer V.; Beyrau, Martina; Woodfin, Abigail; Ody, Christiane; Rourke, Claire; Chavakis, Triantafyllos; Brohi, Karim; Imhof, Beat A.; Nourshargh, Sussan

    2015-01-01

    Summary Breaching endothelial cells (ECs) is a decisive step in the migration of leukocytes from the vascular lumen to the extravascular tissue, but fundamental aspects of this response remain largely unknown. We have previously shown that neutrophils can exhibit abluminal-to-luminal migration through EC junctions within mouse cremasteric venules and that this response is elicited following reduced expression and/or functionality of the EC junctional adhesion molecule-C (JAM-C). Here we demonstrate that the lipid chemoattractant leukotriene B4 (LTB4) was efficacious at causing loss of venular JAM-C and promoting neutrophil reverse transendothelial cell migration (rTEM) in vivo. Local proteolytic cleavage of EC JAM-C by neutrophil elastase (NE) drove this cascade of events as supported by presentation of NE to JAM-C via the neutrophil adhesion molecule Mac-1. The results identify local LTB4-NE axis as a promoter of neutrophil rTEM and provide evidence that this pathway can propagate a local sterile inflammatory response to become systemic. PMID:26047922

  14. Modulation of the heterogeneous membrane potential response of neutrophils to N-formyl-methionyl-leucyl-phenylalanine (FMLP) by leukotriene B4: evidence for cell recruitment

    International Nuclear Information System (INIS)

    Fletcher, M.P.

    1986-01-01

    Individual human neutrophils (PMN) isolated by Hypaque-Ficoll gradient sedimentation, dextran sedimentation, or buffy coat preparation were assessed for the effects of leukotriene B4 (5S,12R dihydroxy 6,14-cis-8, 10 trans eicosatetraenoic acid (LTB4)-pretreatment on N-formylmethionyl-leucyl-phenylalanine (FMLP)-mediated membrane potential or oxidative responses by using flow cytometry and a lipophilic probe of membrane potential (di-pentyl-oxacarbocyanine, di-O-C(5)3), or the nitroblue tetrazolium dye (NBT) reduction test, respectively. Although exposure to LTB4 (10(-7) M) had no effect on the membrane potential of resting PMN and little effect on oxidant production, pretreating PMN with LTB4 followed by FMLP (10(-6) M) demonstrated a significant enhancement in the proportion of depolarizing PMN over that seen with FMLP alone (p = 0.0014, N = 9). This recruitment of previously unresponsive cells by LTB4 was dose and time dependent, with the maximal relative increase in the proportion of depolarizing cells occurring at LTB4 concentrations of 10(-8) to 10(-7) M and within 1 min of LTB4 addition. The recruitment effect persisted despite vigorous washing of the cells. LTB4 also increased the proportion of NBT-positive PMN in response to FMLP. Although LTB4 alone did not depolarize PMN it did induce a light scatter shift indicative of cell activation. 3 H-FMLP binding studied at 0 degree C comparing buffer and LTB4-treated PMN indicated no significant change in the number or affinity of FMLP binding. The data provide evidence for the recruitment of a greater proportion of cells into a FMLP-responsive state as a mechanism for the enhanced functional response of PMN pretreated with LTB4, as well as for a dissociation of the membrane potential and light scattering responses of cells to this pro-inflammatory LT

  15. Control of polyclonal immunoglobulin production from human lymphocytes by leukotrienes; leukotriene B4 induces an OKT8(+), radiosensitive suppressor cell from resting, human OKT8(-) T cells

    International Nuclear Information System (INIS)

    Atluru, D.; Goodwin, J.S.

    1984-01-01

    We report that leukotriene B4 (LTB4), a 5-lipoxygenase metabolite of arachidonic acid, is a potent suppressor of polyclonal Ig production in pokeweed mitogen (PWM)-stimulated cultures of human peripheral blood lymphocytes, while LTC4 and LTD4 have little activity in this system. Preincubation of T cells with LTB4 in nanomolar to picomolar concentrations rendered these cells suppressive of Ig production in subsequent PWM-stimulated cultures of fresh, autologous B + T cells. This LTB4-induced suppressor cell was radiosensitive, and its generation could be blocked by cyclohexamide but not by mitomycin C. The LTB4-induced suppressor cell was OKT8(+), while the precursor for the cell could be OKT8(-). The incubation of OKT8(-) T cells with LTB4 for 18 h resulted in the appearance of the OKT8(+) on 10-20% of the cells, and this could be blocked by cyclohexamide but not by mitomycin C. Thus, LTB4 in very low concentrations induces a radiosensitive OKT8(+) suppressor cell from OKT8(-) cells. In this regard, LTB4 is three to six orders of magnitude more potent than any endogenous hormonal inducer of suppressor cells previously described. Glucocorticosteroids, which block suppressor cell induction in many systems, may act by inhibiting endogenous production of LTB4

  16. Characterization of guinea pig myocardial leukotriene C4 binding sites. Regulation by cations and sulfhydryl-directed reagents

    International Nuclear Information System (INIS)

    Hogaboom, G.K.; Mong, S.; Stadel, J.M.; Crooke, S.T.

    1985-01-01

    Using [ 3 H]leukotriene C4 (LTC4) and radioligand-binding techniques, specific leukotriene C4 binding sites have been identified in membranes derived from guinea pig ventricular myocardium. High performance liquid chromatography analyses indicated that, in the presence of the gamma-glutamyl transpeptidase inhibitor L-serine-borate (80 mM), less than 2% of membrane-bound [ 3 H]LTC4 was converted at 20 degrees to [ 3 H]leukotriene D4 or [ 3 H]leukotriene E4. The specific binding of 4 nM [ 3 H]LTC4, in the presence of 80 mM L-serine-borate, reached a stable steady state within 15 min at 20 degrees (pH 7.5). A monophasic Scatchard plot of saturation binding data yielded a dissociation constant (Kd) of 27.5 +/- 6.0 nM and a maximum number of binding sites (Bmax) of 19.9 +/- 5.2 pmol/mg of membrane protein. Competition binding studies of [ 3 H]LTC4 with synthetic leukotriene C4, leukotriene D4, and leukotriene E4 and the putative peptidoleukotriene antagonists FPL 55712, SKF 88046, and 4R-hydroxy-5S-1-cysteinylglycine-6Z-nonadecanoic acid revealed an order of potency of leukotriene C4 much greater than 4R-hydroxy-5S-1-cysteinylglycine-6Z-nonadecanoic acid greater than SKF 88046 greater than LTE4 greater than LTD4 greater than FPL 55712. The specific [ 3 H]LTC4 binding was stimulated by the divalent cations Ca2+, Mg2+, and Mn2+ and to a lesser degree by the monovalent cations Na+, K+, Li+, and NH4+. CaCl2 (3 mM) and NaCl (150 mM) stimulated the LTC4 binding by increasing the Bmax to 42.6 +/- 5.9 and 35.0 +/- 2.0 pmol/mg, respectively, but had minimal effects on Kd

  17. Characterization of arachidonate 5-lipoxygenase and leukotriene A4 synthetase from RBL-1 cells

    International Nuclear Information System (INIS)

    Cook, M.; Hogaboom, G.K.; Sarau, H.M.; Foley, J.J.; Crooke, S.T.

    1986-01-01

    5-lipoxygenase (LO) and leukotriene (LT) A4 synthetase from RBL-1 high speed (105,000 x g for 60 min) supernatants were partially purified by protein-high performance liquid chromatography (HPLC) and characterized in detail. The partially purified preparation contained only 5-LO and LTA4 synthetase and was isolated from 12-LO, peroxidase and LTA4 hydrolase activities. Reaction products were separated by reversed phase HPLC and quantitated by absorption spectrophotometry and radiochemical detection. The enzyme preparation rapidly converted [ 14 C]arachidonate to [ 14 C]5-hydroperoxyeicosatetraenoic acid (HPETE) and [ 14 C]5,12-dihydroperoxyeicosatetraenoic acids (diHETEs). The 5,12-diHETEs were primarily non-enzymatic breakdown products of LTA4 (e.g., 6-trans-LTB4 and 6-trans-12-epi-LTB4). Both the 5-LO and LTA4 synthetase activities were Ca 2+- and ATP-dependent. For both enzyme activities, the CA 2+ stimulation required the presence of ATP. The fatty acid hydroperoxides, 5-,12-, and 15-HPETE, both stimulated ([ 3 μM]) 5-LO and LTA4 synthetase activities. The rapid isolation and subsequent characterization of 5-LO and LTA4 synthetase provide the bases for the further understanding of the role of the LO pathway in biological processes

  18. Lipoxin A4 stable analogs reduce allergic airway responses via mechanisms distinct from CysLT1 receptor antagonism.

    Science.gov (United States)

    Levy, Bruce D; Lukacs, Nicholas W; Berlin, Aaron A; Schmidt, Birgitta; Guilford, William J; Serhan, Charles N; Parkinson, John F

    2007-12-01

    Cellular recruitment during inflammatory/immune responses is tightly regulated. The ability to dampen inflammation is imperative for prevention of chronic immune responses, as in asthma. Here we investigated the ability of lipoxin A4 (LXA4) stable analogs to regulate airway responses in two allergen-driven models of inflammation. A 15-epi-LXA4 analog (ATLa) and a 3-oxa-15-epi-LXA4 analog (ZK-994) prevented excessive eosinophil and T lymphocyte accumulation and activation after mice were sensitized and aerosol-challenged with ovalbumin. At 50% and to a greater extent than equivalent doses of the CysLT1 receptor antagonist montelukast. Distinct from montelukast, ATLa treatment led to marked reductions in cysteinyl leukotrienes, interleukin-4 (IL-4), and IL-10, and both ATLa and ZK-994 inhibited levels of IL-13. In cockroach allergen-induced airway responses, both intraperitoneal and oral administration of ZK-994 significantly reduced parameters of airway inflammation and hyper-responsiveness in a dose-dependent manner. ZK-994 also significantly changed the balance of Th1/Th2-specific cytokine levels. Thus, the ATLa/LXA4 analog actions are distinct from CysLT1 antagonism and potently block both allergic airway inflammation and hyper-reactivity. Moreover, these results demonstrate these analogs' therapeutic potential as new agonists for the resolution of inflammation.

  19. Leukotriene C4 synthase and ischemic cardiovascular disease and obstructive pulmonary disease in 13,000 individuals

    DEFF Research Database (Denmark)

    Freiberg, Jacob J; Dahl, Morten; Tybjaerg-Hansen, Anne

    2009-01-01

    Ischemic cardiovascular disease and obstructive pulmonary disease involve inflammation. Leukotrienes may be important pro-inflammatory mediators. We tested the hypothesis that the (-1072)G > A and (-444)A > C promoter polymorphisms of leukotriene C4 synthase confer risk of transient ischemic atta...... with risk of asthma or COPD. Leukotriene C4 synthase promoter genotypes influence risk of TIA and ischemic stroke, but not risk of IHD/coronary atherosclerosis, asthma, or COPD....

  20. Leukotrienes are upregulated and associated with human T-lymphotropic virus type 1 (HTLV-1-associated neuroinflammatory disease.

    Directory of Open Access Journals (Sweden)

    Bruno Caetano Trindade

    Full Text Available Leukotrienes (LTs are lipid mediators involved in several inflammatory disorders. We investigated the LT pathway in human T-lymphotropic virus type 1 (HTLV-1 infection by evaluating LT levels in HTLV-1-infected patients classified according to the clinical status as asymptomatic carriers (HACs and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP patients. Bioactive LTB(4 and CysLTs were both increased in the plasma and in the supernatant of peripheral blood mononuclear cell cultures of HTLV-1-infected when compared to non-infected. Interestingly, CysLT concentrations were increased in HAM/TSP patients. Also, the concentration of plasma LTB(4 and LTC(4 positively correlated with the HTLV-1 proviral load in HTLV-1-infected individuals. The gene expression levels of LT receptors were differentially modulated in CD4(+ and CD8(+ T cells of HTLV-1-infected patients. Analysis of the overall plasma signature of immune mediators demonstrated that LT and chemokine amounts were elevated during HTLV-1 infection. Importantly, in addition to CysLTs, IP-10 was also identified as a biomarker for HAM/TSP activity. These data suggest that LTs are likely to be associated with HTLV-1 infection and HAM/TSP development, suggesting their putative use for clinical monitoring.

  1. Concentrations of cysteinyl leukotrienes in urine and bronchoalveolar lavage fluid of cats with experimentally induced asthma.

    Science.gov (United States)

    Norris, Carol R; Decile, Kendra C; Berghaus, Londa J; Berghaus, Roy D; Walby, William F; Schelegle, Edward S; Hyde, Dallas M; Gershwin, Laurel J

    2003-11-01

    To evaluate changes in cysteinyl leukotriene (LT) concentrations in urine and bronchoalveolar lavage fluid (BALF) in cats with experimentally induced asthma. 19 cats with experimentally induced asthma and 5 control cats. Cats were sensitized to Bermuda grass or house dust mite allergen, and phenotypic features of asthma were confirmed with intradermal skin testing, evaluation of BALF eosinophil percentages, and pulmonary function testing. A competitive ELISA kit for LTC4, LTD4, and LTE4 was used for quantitative analysis of LTs. Urinary creatinine concentrations and BALF total protein (TP) concentrations were measured, and urinary LT-to-creatinine ratios and BALF LT-to-TP ratios were calculated. Mean urinary LT-to-creatinine ratios did not differ significantly between control cats and allergen-sensitized cats before or after sensitization and challenge exposure with saline (0.9% NaCl) solution or allergen, respectively. In BALF the mean LT-to-TP ratio of control cats did not differ significantly before or after sensitization and challenge exposure with saline. Asthmatic cats had BALF LT-to-TP ratios that were significantly lower than control cats at all time points, whereas ratios for asthmatic cats did not differ significantly among the various time points. Although LTs were readily detectable in urine, no significant increases in urinary LT concentrations were detected after challenge in allergen-sensitized cats. Spot testing of urinary LT concentrations appears to have no clinical benefit for use in monitoring the inflammatory asthmatic state in cats. The possibility that cysteinyl LTs bind effectively to their target receptors in BALF and, thus, decrease free LT concentrations deserves further study.

  2. Cysteinyl leukotrienes in the urine of patients with liver diseases.

    Science.gov (United States)

    Uemura, M; Buchholz, U; Kojima, H; Keppler, A; Hafkemeyer, P; Fukui, H; Tsujii, T; Keppler, D

    1994-10-01

    The significance of cysteinyl leukotrienes was investigated in patients with liver diseases by measurements of leukotriene E4 and N-acetyl-leukotriene E4 in urine. A marked increase of renal cysteinyl leukotriene excretion was observed in patients with cirrhosis without and with ascites, intrahepatic cholestasis, and obstructive jaundice as compared with healthy subjects (leukotriene E4: means 82, 264, 221 and 142 versus 40 nmol/mol creatinine, respectively; N-acetyl-leukotriene E4: means 25, 64, 61 and 47 versus 13 nmol/mol creatinine, respectively). The urinary concentration of leukotriene E4 was positively correlated with the one of N-acetyl-leukotriene E4 (r = 0.81, p jaundice, the excretion of leukotriene E4 plus N-acetyl-leukotriene E4 was positively correlated with total serum bilirubin. In patients with cirrhosis and in those with obstructive jaundice, the cysteinyl leukotrienes in urine were negatively correlated with creatinine clearance. The elevated renal excretion of cysteinyl leukotrienes decreased after biliary drainage in patients with obstructive jaundice. These data support the concept that increased urinary excretion of cysteinyl leukotrienes in patients with cirrhosis is due to a reduced functional liver mass and that in patients with cholestasis it is mainly due to an impaired elimination into the biliary tract that results in a diversion to renal excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Prostaglandin E2/leukotriene B4 balance induced by Lutzomyia longipalpis saliva favors Leishmania infantum infection.

    Science.gov (United States)

    Araújo-Santos, Théo; Prates, Deboraci Brito; França-Costa, Jaqueline; Luz, Nívea F; Andrade, Bruno B; Miranda, José Carlos; Brodskyn, Claudia I; Barral, Aldina; Bozza, Patrícia T; Borges, Valéria Matos

    2014-12-20

    Eicosanoids and sand fly saliva have a critical role in the Leishmania infection. Here, we evaluated the effect of Lutzomyia longipalpis salivary gland sonicate (SGS) on neutrophil and monocyte recruitment and activation of eicosanoid production in a murine model of inflammation. C57BL/6 mice were inoculated intraperitonealy with Lutzomyia longipalpis SGS or Leishmania infantum or both, followed by analyses of cell recruitment, parasite load and eicosanoid production. Intraperitoneal injection of Lutzomyia longipalpis SGS together with Leishmania infantum induced an early increased parasite viability in monocytes and neutrophils. L. longipalpis SGS increased prostaglandin E2 (PGE2), but reduced leukotriene B4 (LTB4) production ex vivo in peritoneal leukocytes. In addition, the pharmacological inhibition of cyclooxygenase 2 (COX-2) with NS-398 decreased parasite viability inside macrophages during Leishmania infection in the presence of L. longipalpis SGS arguing that PGE2 production is associated with diminished parasite killing. These findings indicate that L. longipalpis SGS is a critical factor driving immune evasion of Leishmania through modulation of PGE2/LTB4 axis, which may represent an important mechanism on establishment of the infection.

  4. Leukotriene Receptor Antagonists in the Treatment of Asthma: Implications for Eosinophilic Inflammation

    Directory of Open Access Journals (Sweden)

    Redwan Moqbel

    1999-01-01

    Full Text Available Recent advances in the treatment and management of asthma have suggested that leukotriene (LT receptor antagonists may be very beneficial as a second generation therapy with steroid-sparing properties and negligible side effects. These agents have shown interesting effects on peripheral blood and sputum eosinophils. A major contributor to the damage in the airway of asthmatic patients is the eosinophil, which, upon activation, releases a battery of granule-associated cytotoxic, cationic proteins, including the major basic protein and eosinophil peroxidase, and membrane-derived de novo-synthesized bioactive lipid mediators, including LTC4, LTD4 and LTE4, as well as platelet activating factor. These products have deleterious effects on the airway tissue including mucosal and smooth muscle layers. Accumulating evidence suggests that these agents may also influence the accumulation and maintenance of eosinophilic responses at the site of inflammation. This article reviews the possible anti-inflammatory mode of action of these therapies. It also discusses where there may be a gap in the knowledge regarding the potential direct and indirect effects of LT modifiers on eosinophil function and recruitment.

  5. [Survival properties of ETEC surface-displayed K88ac-LT(B) on Lactobacillus casei].

    Science.gov (United States)

    Wei, Chunhua; Liu, Jiankui; Hou, Xilin; Wang, Guihua; Yu, Liyun

    2009-01-01

    K88ac-LT(B) gene derived from pQE30-K88ac-LT(B) was cloned into the expression vector pLA and then the recombinant vector was transformed into the competent cells Lactobacillus casei 525. The recombinant bacteria were grown at 37 degrees C, in MRS broth. Western blotting analysis with rabbit-anti-K88ac-LT(B) polyclonal serum indicated that the recombinant protein reacted with the specific antibodies. The results showed that the molecular weight of the recombinant protein was about 71.2 kD. The K88ac-LT(B) fusion protein on the cell surface was confirmed by immunofluorescence mciroscopy and flow cytometric analysis. In addition, the survival of recombinant Lactobacillus casei 525 was studied in imitative gastrointestinal environments such as artificial gastro fluid (pH 1.5-5.5), artificial intestinal fluid, bile(0.3-3.0 g/L). The results indicated that the recombinant strain survived well in artificial gastric fluids at pH 2.5-4.5 in 5 h. The recombinant Lactobacillus casei 525 could slowly grow in the artificial intestinal fluid for different time, and could survive in 0.3% bile.

  6. Metabolism of leukotriene B4 to dihydro and dihydro-oxo products by porcine leukocytes

    International Nuclear Information System (INIS)

    Powell, W.S.; Gravelle, F.

    1989-01-01

    Porcine leukocytes contain a novel pathway for the metabolism of leukotriene B4 (LTB4) which results in reduction of the conjugated triene chromophore to a conjugated diene. These cells converted LTB4 to two major metabolites, both of which exhibited maximal absorbance at 230 nm in their UV spectra. These products were purified by high pressure liquid chromatography and identified as 10, 11-dihydro-LTB4 and 10,11-dihydro-12-oxo-LTB4 on the basis of the mass spectra of various derivatives. The position of the double bond of LTB4 which had been reduced was established by cleaving the remaining double bonds of 10, 11-dihydro-LTB4 with ozone followed by oxidation or reduction of the resulting ozonide and analysis of the products by mass spectrometry. Experiments with deuterium-labeled substrate indicated that LTB4 could be directly converted to 10, 11-dihydro-LTB4 without the prior oxidation of either of its hydroxyl groups, as is required for the formation of dihydro metabolites of prostaglandins. Incubation of porcine leukocytes with 10, 11-dihydro-LTB4 and 10, 11-dihydro-12-oxo-LTB4 indicated that these two products can be interconverted and are in equilibrium with one another. The dihydro-oxo metabolite can therefore be formed from 10, 11-dihydro-LTB4, although we have not ruled out the possibility that it is also produced via 12-oxo-LTB4, which could be a transitory intermediate. These results indicate that porcine leukocytes contain a novel reductase/dehydrogenase pathway distinct from the pathway responsible for the metabolism of prostaglandins. This pathway is also different from the pathway in human polymorphonuclear leukocytes which converts 6-trans-isomers of LTB4 to dihydro products, since the latter pathway involves 5-oxo intermediates and results in a shift in the positions of the remaining double bonds

  7. Resveratrol, a Red Wine Polyphenol, Suppresses Pancreatic Cancer by Inhibiting Leukotriene A4 Hydrolase

    Science.gov (United States)

    Oi, Naomi; Jeong, Chul-Ho; Nadas, Janos; Cho, Yong-Yeon; Pugliese, Angelo; Bode, Ann M.; Dong, Zigang

    2016-01-01

    The anticancer effects of red wine have attracted considerable attention. Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a well-known polyphenolic compound of red wine with cancer chemopreventive activity. However, the basis for this activity is unclear. We studied leukotriene A4 hydrolase (LTA4H) as a relevant target in pancreatic cancer. LTA4H knockdown limited the formation of leukotriene B4 (LTB4), the enzymatic product of LTA4H, and suppressed anchorage-independent growth of pancreatic cancer cells. An in silico shape similarity algorithm predicted that LTA4H might be a potential target of resveratrol. In support of this idea, we found that resveratrol directly bound to LTA4H in vitro and in cells and suppressed proliferation and anchorage-independent growth of pancreatic cancer by inhibiting LTB4 production and expression of the LTB4 receptor 1 (BLT1). Notably, resveratrol exerted relatively stronger inhibitory effects than bestatin, an established inhibitor of LTA4H activity, and the inhibitory effects of resveratrol were reduced in cells where LTA4H was suppressed by shRNA-mediated knockdown. Importantly, resveratrol inhibited tumor formation in a xenograft mouse model of human pancreatic cancer by inhibiting LTA4H activity. Our findings identify LTA4H as a functionally important target for mediating the anticancer properties of resveratrol. PMID:20952510

  8. Leukotriene B4 omega-hydroxylase in human polymorphonuclear leukocytes. Suicidal inactivation by acetylenic fatty acids.

    Science.gov (United States)

    Shak, S; Reich, N O; Goldstein, I M; Ortiz de Montellano, P R

    1985-10-25

    Human polymorphonuclear leukocytes (PMN) not only generate and respond to leukotriene B4 (LTB4), but also catabolize this mediator of inflammation rapidly and specifically by omega-oxidation (probably due to the action of a cytochrome P-450 enzyme). To develop pharmacologically useful inhibitors of the LTB4 omega-hydroxylase in human PMN, we devised a general scheme for synthesizing terminal acetylenic fatty acids based on the "acetylenic zipper" reaction. We found that the LTB4 omega-hydroxylase in intact PMN and in PMN sonicates is inactivated in a concentration-dependent fashion by terminal acetylenic analogues of lauric, palmitic, and stearic acids (i.e. 11-dodecynoic, 15-hexadecynoic, and 17-octadecynoic acids). Consistent with a suicidal process, inactivation of the LTB4 omega-hydroxylase requires molecular oxygen and NADPH, is time-dependent, and follows pseudo-first-order kinetics. Inactivation of the omega-hydroxylase by acetylenic fatty acids also is dependent on the terminal acetylenic moiety and the carbon chain length. Saturated fatty acids lacking a terminal acetylenic moiety do not inactivate the omega-hydroxylase. In addition, the two long-chain (C16, C18) acetylenic fatty acids inactivate the omega-hydroxylase at much lower concentrations (less than 5.0 microM) than those required for inactivation by the short-chain (C12) terminal acetylenic fatty acid (100 microM). Potent suicidal inhibitors of the LTB4 omega-hydroxylase in human PMN will help elucidate the roles played by LTB4 and its omega-oxidation products in regulating PMN function and in mediating inflammation.

  9. Cysteinyl-Leukotriene Receptors and Cellular Signals

    Directory of Open Access Journals (Sweden)

    G. Enrico Rovati

    2007-01-01

    Full Text Available Cysteinyl-leukotrienes (cysteinyl-LTs exert a range of proinflammatory effects, such as constriction of airways and vascular smooth muscle, increase of endothelial cell permeability leading to plasma exudation and edema, and enhanced mucus secretion. They have proved to be important mediators in asthma, allergic rhinitis, and other inflammatory conditions, including cardiovascular diseases, cancer, atopic dermatitis, and urticaria. The classification into subtypes of the cysteinyl-LT receptors (CysLTRs was based initially on binding and functional data, obtained using the natural agonists and a wide range of antagonists. CysLTRs have proved remarkably resistant to cloning. However, in 1999 and 2000, the CysLT1R and CysLT2R were successfully cloned and both shown to be members of the G-protein coupled receptors (GPCRs superfamily. Molecular cloning has confirmed most of the previous pharmacological characterization and identified distinct expression patterns only partially overlapping. Recombinant CysLTRs couple to the Gq/11 pathway that modulates inositol phospholipids hydrolysis and calcium mobilization, whereas in native systems, they often activate a pertussis toxin-insensitive Gi/o-protein, or are coupled promiscuously to both G-proteins. Interestingly, recent data provide evidence for the existence of an additional receptor subtype that seems to respond to both cysteinyl-LTs and uracil nucleosides, and of an intracellular pool of CysLTRs that may have roles different from those of plasma membrane receptors. Finally, a cross-talk between the cysteinyl-LT and the purine systems is being delineated. This review will summarize recent data derived from studies on the molecular and cellular pharmacology of CysLTRs.

  10. A novel formulation of L-thyroxine (L-T4) reduces the problem of L-T4 malabsorption by coffee observed with traditional tablet formulations.

    Science.gov (United States)

    Vita, Roberto; Saraceno, Giovanna; Trimarchi, Francesco; Benvenga, Salvatore

    2013-02-01

    The purpose of this work is to evaluate if the coffee-associated malabsorption of tablet levothyroxine (L-T4) is reduced by soft gel capsule. We recruited 8 patients with coffee-associated L-T4 malabsorption including one hypothyroid patient. For 6 months, the patients were switched to the capsule maintaining the L-T4 daily dose. Patients took the capsule with water, having coffee 1 h later (proper habit, PH) on days 1-90, or with coffee ≤ 5 min later (improper habit, IH) on days 91-180. After 6 months, 2 patients volunteered for an acute loading test of 600 μg L-T4 (capsule) ingested with water (PH) or with coffee (IH). In the single hypothyroid patient, the post-switch TSH ranged 0.06-0.16 mU/L (PH) versus 5.8-22.4 mU/L pre-switch (PH) and 0.025-0.29 mU/L (IH) versus 26-34 mU/L pre-switch (IH). In the other 7 patients, post-switch TSH was 0.41 ± 0.46 (PH) versus 0.28 ± 0.20 pre-switch (PH) (P = 0.61) and 0.34 ± 0.30 (IH) versus 1.23 ± 1.47 pre-switch (IH) (P coffee influenced L-T4 pharmacokinetics minimally. Soft gel capsules can be used in patients who are unable/unwilling to change their IH of taking L-T4.

  11. Leukotriene-B4 concentrations in exhaled breath condensate and lung function after thirty minutes of breathing technically dried compressed air.

    Science.gov (United States)

    Neubauer, Birger; Struck, Niclas; Mutzbauer, Till S; Schotte, Ulrich; Langfeldt, Norbert; Tetzlaff, Kay

    2002-01-01

    In previous studies it had been shown that leukotriene-B4 [LTB4] concentrations in the exhaled breath mirror the inflammatory activity of the airways if the respiratory tract has been exposed to occupational hazards. In diving the respiratory tract is exposed to cold and dry air and the nasopharynx, as the site of breathing-gas warming and humidification, is bypassed. The aim of the present study was to obtain LTB4-concentrations in the exhaled breath and spirometric data of 17 healthy subjects before and after thirty minutes of technically dried air breathing at normobar ambient pressure. The exhaled breath was collected non-invasively, via a permanently cooled expiration tube. The condensate was measured by a standard enzyme immunoassay for LTB4. Lung function values (FVC, FEV1, MEF 25, MEF 50) were simultaneously obtained by spirometry. The measured pre- and post-exposure LTB4- concentrations as well as the lung function values were in the normal range. The present data gave no evidence for any inflammatory activity in the subjects' airways after thirty minutes breathing technically dried air.

  12. In vivo formation of beta-oxidized metabolites of leukotriene E4 in the rat

    International Nuclear Information System (INIS)

    Perrin, P.; Zirrolli, J.; Stene, D.O.; Lellouche, J.P.; Beaucourt, J.P.; Murphy, R.C.

    1989-01-01

    Intraperitoneal administration of [ 3 H]-leukotriene E4 in the rat resulted in the appearance of radiolabel in urine and feces. Separation of polar urinary metabolites and chromatographic comparison of synthetic metabolites indicated the in vivo formation of omega-oxidized metabolites of LTE4 with sequential beta-oxidation. Furthermore, the metabolite identified as 16-carboxy-17,18,19,20-tetranor-14,15-dihydro-N-acetyl-LTE4 substantiates the biochemical pathway of beta-oxidation in vivo involving the 2,4-dienoyl CoA reductase as an integral step. These results substantiate beta-oxidation of sulfidopeptide leukotrienes in vivo and these metabolites account for some of the major urinary metabolites of this class of lipid mediator

  13. Kinetic studies on binding of thyroid hormones (L-T3 and L-T4) to the receptors of lymphocyte cells isolated from uraemia subjects

    International Nuclear Information System (INIS)

    Al-Sultani, A.S.J.

    1989-01-01

    The levels of L-T 3 , L-T 4 and TSH in uremic sera have been measured by (RIA), and shown to have a decrease in both L-T 3 and L-T 4 levels with normal level of TSH for most specimens used in this study. Kinetics properties for binding of thyroid hormones L-T 3 and L-T 4 with nuclear receptors of human lymphocyte cells extracted from uremic patient have been studied and compared this result with control and hypothyroidism subjects and we obtained that uremic condition have a large effect on these nuclear receptors properties. Dissociation constant (K d ) and maximal binding capacity (MBC) of both L-T 3 and L-T 4 with these nuclear receptors have been determined, and we obtained that uremic condition did not affect on (K d ) values for both L-T 3 and L-T 4 but it affected on (MBC) values compared with normal subject. 8 tabs.; 25 figs.; 203 refs

  14. Significance of production of peptide leukotrienes in murine traumatic shock

    International Nuclear Information System (INIS)

    Craft, D.V.; Lefer, D.J.; Hock, C.E.; Lefer, A.M.

    1986-01-01

    The authors studied the formation of a leukotriene metabolite in plasma and bile during traumatic shock. Anesthetized rats subjected to Noble-Collip drum trauma developed a lethal shock state characterized by a survival time of 1.9 +/- 0.3h, a 4.5-fold increase in plasma cathepsin D activity, and a reduction in mean arterial blood pressure to 45 +/- 2 mmHg compared with 108 +/- 5 mmHg in sham-shock controls. Plasma and bile samples were analyzed by reverse-phase high-pressure liquid chromatography (HPLC) for peptide leukotrienes, and their retention times were confirmed by co-elution with radioactive standards, radioimmunoassay (RIA), and UV spectrophotometry. No leukotrienes or metabolites were found in plasma. The major peptide leukotriene from bile was eluted between LTC 4 and LTD 4 and corresponds to a metabolite of LTE 4 , N-acetyl-LTE 4 , which is also produced during endotoxin shock. The metabolite increased nearly sevenfold in traumatic shock compared with sham trauma. The identity of the metabolite was confirmed by UV scan, which revealed a spectrum consistent with a peptide leukotriene and similar to that of previously reported spectra for N-acetyl-LTE 4 . In conclusion, peptide leukotrienes are rapidly cleared from the blood and appear in the bile as N-acetyl-LTE 4 , a metabolite of the peptide leukotrienes. These findings support a role of the peptide leukotrienes in the pathogenesis of traumatic shock

  15. Hypercholesterolemia Increases the Production of Leukotriene B4 in Neutrophils by Enhancing the Nuclear Localization of 5-Lipoxygenase

    Directory of Open Access Journals (Sweden)

    Xiao-Feng Lai

    2014-11-01

    Full Text Available Aims: Neutrophils can synthesize leukotriene B4 (LTB4 by activating the 5-lipoxygenase (5-LOsignaling pathway. LTB4 is a pro-inflammatory mediator associated with the etiology and progression of atherosclerosis. It can increase function and number of neutrophils in an autocrine manner. Since hypercholesterolemia is associated with an increase in the number and function of neutrophils, we hypothesized that this effect could be mediated through increased production of LTB4 in neutrophils. Methods/Results: Hypercholesterolemia was modeled in Wistar rats by feeding them with a high cholesterol diet. The induction of hypercholesterolemia caused an increase in the plasma levels of LTB4, following lipopolysaccharide stimulation. This effect was recapitulated in vitro, both in the presence and absence of stimulation with the activator of 5-LO, A23187. Neutrophils in hypercholesterolemia rats expressed similar total levels of 5-LO as control rats, but displayed increased nuclear localization of 5-LO, as well as elevated levels of phosphorylated 5-LO and ERK1/2. In vitro, MβCD/cholesterol complexes enriched cholesterol in neutrophils, resulted in similar changes in 5-LO/LTB4. In addition, these alterations could be inhibited with the ERK inhibitor PD98059. Conclusion: Hypercholesterolemia increases LTB4 production in neutrophils by increasing the nuclear localization of 5-LO, which is the result of its phosphorylation by activated ERK1/2.

  16. CysLT2 receptor activation is involved in LTC4-induced lung air-trapping in guinea pigs.

    Science.gov (United States)

    Sekioka, Tomohiko; Kadode, Michiaki; Yonetomi, Yasuo; Kamiya, Akihiro; Fujita, Manabu; Nabe, Takeshi; Kawabata, Kazuhito

    2017-01-05

    CysLT 1 receptors are known to be involved in the pathogenesis of asthma. However, the functional roles of CysLT 2 receptors in this condition have not been determined. The purpose of this study is to develop an experimental model of CysLT 2 receptor-mediated LTC 4 -induced lung air-trapping in guinea pigs and use this model to clarify the mechanism underlying response to such trapping. Because LTC 4 is rapidly converted to LTD 4 by γ-glutamyltranspeptidase (γ-GTP) under physiological conditions, S-hexyl GSH was used as a γ-GTP inhibitor. In anesthetized artificially ventilated guinea pigs with no S-hexyl GSH treatment, i.v. LTC 4 -induced bronchoconstriction was almost completely inhibited by montelukast, a CysLT 1 receptor antagonist, but not by BayCysLT 2 RA, a CysLT 2 receptor antagonist. The inhibitory effect of montelukast was diminished by treatment with S-hexyl GSH, whereas the effect of BayCysLT 2 RA was enhanced with increasing dose of S-hexyl GSH. Macroscopic and histological examination of lung tissue isolated from LTC 4 -/S-hexyl-GSH-treated guinea pigs revealed air-trapping expansion, particularly at the alveolar site. Inhaled LTC 4 in conscious guinea pigs treated with S-hexyl GSH increased both airway resistance and airway hyperinflation. On the other hand, LTC 4 -induced air-trapping was only partially suppressed by treatment with the bronchodilator salmeterol. Although montelukast inhibition of LTC 4 -induced air-trapping was weak, treatment with BayCysLT 2 RA resulted in complete suppression of this air-trapping. Furthermore, BayCysLT 2 RA completely suppressed LTC 4 -induced airway vascular hyperpermeability. In conclusion, we found in this study that CysLT 2 receptors mediate LTC 4 -induced bronchoconstriction and air-trapping in S-hexyl GSH-treated guinea pigs. It is therefore believed that CysLT 2 receptors contribute to asthmatic response involving air-trapping. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Esculetin reduces leukotriene B4 level in plasma of rats with adjuvant-induced arthritis

    Directory of Open Access Journals (Sweden)

    Przemysław Rzodkiewicz

    2016-10-01

    Full Text Available Objectives : Esculetin (6,7-dihydroxycoumarin is a natural coumarin with anti-oxidant, anti-inflammatory and anti-nociceptive activity. It acts as a potent inhibitor of lipoxygenases (5-LOX and 12-LOX and decreases the production of matrix metalloproteinases (MMP-1, MMP-3 and MMP-9. Because both inhibition of lipoxygenases and inhibition of matrix metalloproteinases are effective strategies in the treatment of rheumatoid arthritis, we investigated whether esculetin may be effective in adjuvant-induced arthritis in rats. Material and methods : The study was performed on male Lewis rats, in the adjuvant-induced arthritis model. Rats were divided into two groups: control (treated with 1% methylcellulose and experimental (treated with esculetin – 10 mg/kg ip.. The tested compound was administered for 5 consecutive days starting on the 21st day after induction of arthritis. Each group consisted of 7 animals. After 5 days of treatment, rats were anesthetized. The concentration of leukotriene B4 (LTB4 in plasma was determined by a competitive enzyme immunoassay. Results : The LTB4 level in plasma of rats with adjuvant-induced arthritis is increased in comparison to rats without inflammation (362 ±34 vs. 274 ±15 pg/ml, p < 0.01, respectively. Five-day treatment with esculetin in adjuvant-induced arthritis rats decreases the LTB4 level to a level comparable with rats without inflammation (284 ±23 pg/ml, p < 0.01. Conclusions : LTB4 is the most potent chemotactic agent influencing neutrophil migration into the joint. It is known that its level in serum of patients with active rheumatoid arthritis is increased and correlates with disease severity. Some other lipoxygenase inhibitors have already been tested as potential drug candidates in clinical and preclinical trials for rheumatoid arthritis (Zileuton, PF-4191834. Because esculetin decreases the LTB4 level in plasma of rats in adjuvant-induced arthritis, it may also be considered as an attractive

  18. The leukotriene B{sub 4} receptor, BLT1, is required for the induction of experimental autoimmune encephalomyelitis

    Energy Technology Data Exchange (ETDEWEB)

    Kihara, Yasuyuki, E-mail: kihara-yasuyuki@umin.net [Department of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Yokomizo, Takehiko [Department of Medical Biochemistry, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582 (Japan); Core Research for Embryonic Science and Technology (CREST), Japan Science and Technology Agency (Japan); Kunita, Akiko; Morishita, Yasuyuki; Fukayama, Masashi [Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033 (Japan); Ishii, Satoshi; Shimizu, Takao [Department of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)

    2010-04-09

    Leukotriene B{sub 4} (LTB{sub 4}) is a potent chemoattractant and activator of neutrophils, macrophages and T cells. These cells are a key component of inflammation and all express BLT1, a high affinity G-protein-coupled receptor for LTB{sub 4}. However, little is known about the neuroimmune functions of BLT1. In this study, we describe a distinct role for BLT1 in the pathology of experimental autoimmune encephalomyelitis (EAE) and T{sub H}1/T{sub H}17 immune responses. BLT1 mRNA was highly upregulated in the spinal cord of EAE mice, especially during the induction phase. BLT1{sup -/-} mice had delayed onset and less severe symptoms of EAE than BLT1{sup +/+} mice. Additionally, inflammatory cells were recruited to the spinal cord of asymptomatic BLT1{sup +/+}, but not BLT1{sup -/-} mice before the onset of disease. Ex vivo studies showed that both the proliferation and the production of IFN-{gamma}, TNF-{alpha}, IL-17 and IL-6 were impaired in BLT1{sup -/-} cells, as compared with BLT1{sup +/+} cells. Thus, we suggest that BLT1 exacerbates EAE by regulating the migration of inflammatory cells and T{sub H}1/T{sub H}17 immune responses. Our findings provide a novel therapeutic option for the treatment of multiple sclerosis and other T{sub H}17-mediated diseases.

  19. Vascular effects of leukotriene D4 in human skin

    DEFF Research Database (Denmark)

    Bisgaard, H

    1987-01-01

    Leukotriene D4 (LTD4) increased the blood flow rate in human skin, equipotent to histamine in the dose range of 3.1-200 pmol. The vasodilatation lasted for up to 60 min, and no late reactions occurred. Indomethacin did not affect the LTD4-induced blood flow rate. H1 and H2 antagonists reduced...... as a mediator of the axon reflex, and show that LTD4 causes a direct vasodilatory effect that is not mediated via histamine or cyclooxygenase products. The laser-Doppler flowmeter was applied for dynamic studies of the vasopressor response in the skin during a Valsalva maneuver, and the relative changes...

  20. Effects of menadione, a reactive oxygen generator, on leukotriene secretion from RBL-2H3 cells.

    Science.gov (United States)

    Kawamura, Fumio; Nakanishi, Mamoru; Hirashima, Naohide

    2010-01-01

    Reactive oxygen species (ROS) are produced in various cells and affect many biological processes. We previously reported that 2-methyl-1,4-naphtoquinone (menadione) inhibited Ca(2+) influx from the extracellular medium and exocytosis evoked by antigen stimulation in the mast cell line, RBL-2H3. Mast cells release various inflammatory mediators such as leukotrienes (LTs) and cytokines in addition to the exocytotic secretion of histamine. In this study, we investigated the effects of menadione on LT release in RBL-2H3. Treatment of RBL cells with menadione inhibited LTC(4) secretion induced by antigen stimulation. To elucidate the mechanism of this inhibition, we examined the effects of menadione on the activation process of 5-lipoxygenase that is responsible for the synthesis of LTs from arachidonic acid. Menadione did not affect the phosophorylation of mitogen activated protein (MAP) kinases, extracellular signal-regulated kinase (ERK) and p38, which regulates phosphorylation of 5-lipoxygenase. However, menadione inhibited the translocation of 5-lipoxygenase from the cytoplasm to the nuclear membrane. Together with the result that LT secretion was severely impaired in the absence of extracellular Ca2(2+), it is suggested that ROS produced by menadione inhibited LT secretion through impaired Ca2(2+) influx and 5-lipoxygenase translocation to the nuclear membrane.

  1. A role for inflammatory mediators in heterologous desensitization of CysLT1 receptor in human monocytes

    Science.gov (United States)

    Capra, Valérie; Accomazzo, Maria Rosa; Gardoni, Fabrizio; Barbieri, Silvia; Rovati, G. Enrico

    2010-01-01

    Cysteinyl-leukotrienes (cysteinyl-LT) are rapidly generated at sites of inflammation and, in addition to their role in asthma, rhinitis, and other immune disorders, are increasingly regarded as significant inflammatory factors in cancer, gastrointestinal, cardiovascular diseases. We recently demonstrated that in monocyte/macrophage–like U937 cells, extracellular nucleotides heterologously desensitize CysLT1 receptor (CysLT1R)-induced Ca2+ transients. Given that monocytes express a number of other inflammatory and chemoattractant receptors, this study was aimed at characterizing transregulation between these different stimuli. We demonstrate that in U937 cells and in primary human monocytes, a series of inflammatory mediators activating Gi-coupled receptor (FPR1, BLT1) desensitize CysLT1R-induced Ca2+ response unidirectionally through activation of PKC. Conversely, PAF-R, exclusively coupled to Gq, cross-desensitizes CysLT1R without the apparent involvement of any kinase. Interestingly, Gs-coupled receptors (β2AR, H1/2R, EP2/4R) are also able to desensitize CysLT1R response through activation of PKA. Heterologous desensitization seems to affect mostly the Gi-mediated signaling of the CysLT1R. The hierarchy of desensitization among agonists may be important for leukocyte signal processing at the site of inflammation. Considering that monocytes/macrophages are likely to be the major source of cysteinyl-LT in many immunological and inflammatory processes, shedding light on how their receptors are regulated will certainly help to better understand the role of these cells in orchestrating this complex network of integrated signals. PMID:19965602

  2. Leukotriene B4 omega-hydroxylase in human polymorphonuclear leukocytes. Partial purification and identification as a cytochrome P-450.

    Science.gov (United States)

    Shak, S; Goldstein, I M

    1985-09-01

    Human polymorphonuclear leukocytes (PMN) not only synthesize and respond to leukotriene B4 (LTB4), but also catabolize this mediator of inflammation rapidly and specifically by omega-oxidation. To characterize the enzyme(s) responsible for omega-oxidation of LTB4, human PMN were disrupted by sonication and subjected to differential centrifugation to yield membrane, granule, and cytosol fractions (identified by biochemical markers). LTB4 omega-hydroxylase activity was concentrated (together with NADPH cytochrome c reductase activity) only in the membrane fraction (specific activity increased 10-fold as compared to whole sonicates, 41% recovery). Negligible activity was detected in granule or cytosol fractions. LTB4 omega-hydroxylase activity in isolated PMN membranes was linear with respect to duration of incubation and protein concentration, was maximal at pH 7.4, had a Km for LTB4 of 0.6 microM, and was dependent on oxygen and on reduced pyridine nucleotides (apparent Km for NADPH = 0.5 microM; apparent Km for NADH = 223 microM). The LTB4 omega-hydroxylase was inhibited significantly by carbon monoxide, ferricytochrome c, SKF-525A, and Triton X-100, but was not affected by alpha-naphthoflavone, azide, cyanide, catalase, and superoxide dismutase. Finally, isolated PMN membranes exhibited a carbon monoxide difference spectrum with a peak at 452 nm. Thus, we have partially purified the LTB4 omega-hydroxylase in human PMN and identified the enzyme as a membrane-associated, NADPH-dependent cytochrome P-450.

  3. Evidence for eosinophil recruitment, leukotriene B4 production and mast cell hyperplasia following Toxocara canis infection in rats

    Directory of Open Access Journals (Sweden)

    D. Carlos

    2011-04-01

    Full Text Available It is well known that eosinophilia is a key pathogenetic component of toxocariasis. The objective of the present study was to determine if there is an association between peritoneal and blood eosinophil influx, mast cell hyperplasia and leukotriene B4 (LTB4 production after Toxocara canis infection. Oral inoculation of 56-day-old Wistar rats (N = 5-7 per group with 1000 embryonated eggs containing third-stage (L3 T. canis larvae led to a robust accumulation of total leukocytes in blood beginning on day 3 and peaking on day 18, mainly characterized by eosinophils and accompanied by higher serum LTB4 levels. At that time, we also noted increased eosinophil numbers in the peritoneal cavity. In addition, we observed increased peritoneal mast cell number in the peritoneal cavity, which correlated with the time course of eosinophilia during toxocariasis. We also demonstrated that mast cell hyperplasia in the intestines and lungs began soon after the T. canis larvae migrated to these compartments, reaching maximal levels on day 24, which correlated with the complete elimination of the parasite. Therefore, mast cells appear to be involved in peritoneal and blood eosinophil infiltration through an LTB4-dependent mechanism following T. canis infection in rats. Our data also demonstrate a tight association between larval migratory stages and intestinal and pulmonary mast cell hyperplasia in the toxocariasis model.

  4. Distinct cellular sources of hepoxilin A3 and leukotriene B4 are used to coordinate bacterial-induced neutrophil transepithelial migration.

    Science.gov (United States)

    Pazos, Michael A; Pirzai, Waheed; Yonker, Lael M; Morisseau, Christophe; Gronert, Karsten; Hurley, Bryan P

    2015-02-01

    Neutrophilic infiltration is a leading contributor to pathology in a number of pulmonary disease states, including cystic fibrosis. Hepoxilin A3 (HXA3) is a chemotactic eicosanoid shown to mediate the transepithelial passage of neutrophils in response to infection in several model systems and at multiple mucosal surfaces. Another well-known eicosanoid mediating general neutrophil chemotaxis is leukotriene B4 (LTB4). We sought to distinguish the roles of each eicosanoid in the context of infection of lung epithelial monolayers by Pseudomonas aeruginosa. Using human and mouse in vitro transwell model systems, we used a combination of biosynthetic inhibitors, receptor antagonists, as well as mutant sources of neutrophils to assess the contribution of each chemoattractant in driving neutrophil transepithelial migration. We found that following chemotaxis to epithelial-derived HXA3 signals, neutrophil-derived LTB4 is required to amplify the magnitude of neutrophil migration. LTB4 signaling is not required for migration to HXA3 signals, but LTB4 generation by migrated neutrophils plays a significant role in augmenting the initial HXA3-mediated migration. We conclude that HXA3 and LTB4 serve independent roles to collectively coordinate an effective neutrophilic transepithelial migratory response. Copyright © 2015 by The American Association of Immunologists, Inc.

  5. Identification of leukotriene D4 specific binding sites in the membrane preparation isolated from guinea pig lung

    International Nuclear Information System (INIS)

    Mong, S.; Wu, H.L.; Clark, M.A.; Stadel, J.M.; Gleason, J.G.; Crooke, S.T.

    1984-01-01

    A radioligand binding assay has been established to study leukotriene specific binding sites in the guinea pig and rabbit tissues. Using high specific activity [ 3 H]-leukotriene D4 [( 3 H]-LTD4), in the presence or absence of unlabeled LTD4, the diastereoisomer of LTD4 (5R,6S-LTD4), leukotriene E4 (LTE4) and the end-organ antagonist, FPL 55712, the authors have identified specific binding sites for [ 3 H]-LTD4 in the crude membrane fraction isolated from guinea pig lung. The time required for [ 3 H]-LTD4 binding to reach equilibrium was approximately 20 to 25 min at 37 degrees C in the presence of 10 mM Tris-HCl buffer (pH 7.5) containing 150 mM NaCl. The binding of [ 3 H]-LTD4 to the specific sites was saturable, reversible and stereospecific. The maximal number of binding sites (Bmax), derived from Scatchard analysis, was approximately 320 +/- 200 fmol per mg of crude membrane protein. The dissociation constants, derived from kinetic and saturation analyses, were 9.7 nM and 5 +/- 4 nM, respectively. The specific binding sites could not be detected in the crude membrane fraction prepared from guinea pig ileum, brain and liver, or rabbit lung, trachea, ileum and uterus. In radioligand competition experiments, LTD4, FPL 55712 and 5R,6S-LTD4 competed with [ 3 H]-LTD4. The metabolic inhibitors of arachidonic acid and SKF 88046, an antagonist of the indirectly-mediated actions of LTD4, did not significantly compete with [ 3 H]-LTD4 at the specific binding sites. These correlations indicated that these specific binding sites may be the putative leukotriene receptors in the guinea-pig lung

  6. Increasing doses effect of L-T4 and L-T3 in the hypothalamus - hypophysis - thyroid in patients carrier of congenital and acquired hypothyroidism

    International Nuclear Information System (INIS)

    Cavaliere, H.

    1987-01-01

    The pituitary and peripheral response to L-T4 and L-T3 therapy were studied in 12 patients with congenital goitrous hypothyroidism, in 10 patients with an ectopic thyroid and onset of hypothyroidism at 3-8 years of age, and in 6 patients with adult-onset hypothyroidism, after they had had their chronic thyroid hormone replacement therapy discontinued for 30 days. They were first treated with increasing L-T4 (0.1, 0.2, and 0.4 mg daily) followed by L-T3 (0.05 and 0.2 mg daily) after stopping thyroid medication for another month. Ten normal subjects were treated identically. Since all patients received similar doses of thyroid hormones (μg/Kg of body weight) and had similar serum levels of T4 and T3 on each dose of L-T4 or L-T3, this paper concludes that congenitally hypothyroid patients have persistent pituitary resistance, but no peripheral resistance, to thyroid hormone. (author)

  7. A Systematic Review of Clinical Practice Guidelines' Recommendations on Levothyroxine Therapy Alone versus Combination Therapy (LT4 plus LT3) for Hypothyroidism.

    Science.gov (United States)

    Kraut, Eyal; Farahani, Pendar

    2015-12-04

    Patients with hypothyroidism are increasingly enquiring about the benefit of using combination therapy of levothyroxine (LT4) and liothyronine (LT3) as a potential treatment for hypothyroidism. Combination therapy, however, remains controversial. The purpose of this study was to systematically review available hypothyroidism treatment recommendations from clinical practice guidelines from around the world to identify the consensus regarding combination therapy. Clinical practice guidelines were obtained from searches of PubMed, EMBASE, and MEDLINE, using several combinations of MeSH terms. The search was limited to clinical guidelines in English-language publications, published between January 1, 1990 and May 1, 2015. A quantitative approach was utilized for data synthesis. Thirteen guidelines were identified, including three regarding pregnancy, two regarding pediatric populations and eight regarding adult populations. There were six guidelines from North America, four guidelines from Europe and three guidelines from South America. Twelve of the guidelines were published after 2010. Nine guidelines addressed combination therapy of LT4 plus LT3, and all nine concluded that LT4 therapy alone is the standard of care, with insufficient evidence to recommend widespread combination therapy. Only the 2012 ETA Guidelines and the 2015 BTA Guidelines concluded that combination therapy could be used, although only in certain circumstances and as an experimental treatment. This systematic review illustrates that clinical practice guidelines worldwide do not recommend and do not support routine use of combination LT4 and LT3 therapy to treat hypothyroidism.

  8. Effects of 18 months of L-T4 replacement in women with subclinical hypothyroidism.

    LENUS (Irish Health Repository)

    Adrees, M

    2012-02-01

    CONTEXT: Some of the cardiovascular and renal abnormalities seen in overt hypothyroidism have also been reported in subclinical hypothyroidism (SCH). Short-term L-T4 replacement in SCH improves cardiovascular risk markers and reduces carotid intima-media thickness (CIMT), a surrogate marker of atherosclerosis. The haemodynamic and renal effects of L-T4 replacement in SCH are poorly understood. OBJECTIVES: To compare cardiovascular risk factors and renal variables in women with SCH and normal women. To study the effects of L-T4 replacement in SCH subjects on these variables and on structural and functional changes in common carotid and brachial arteries. DESIGN: Fifty-six women with SCH before and after L-T4 replacement for 18 months and 56 normal women of similar age distribution were studied. Blood Pressure (BP), plasma lipids and homocysteine were measured and renal function evaluated [estimation of glomerular filtration rate (eGFR) using standard equations and measurement of serum Cystatin-C] in women with SCH before and after 18 months of l-T4, and in healthy women. CIMT and endothelial function (using brachial artery ultrasound) were studied before and after L-T4 in a subgroup of women with SCH. RESULTS: Systolic and diastolic BP, total cholesterol, triglyceride, LDL-cholesterol, lipoprotein(a) and homocysteine were greater in SCH (P < 0.05), and following L-T4 replacement decreased (P < 0.05) to levels that no longer differed from normal subjects. Estimated GFR was reduced and serum Cystatin-C increased (P < 0.05) in SCH. These variables also normalized following L-T4. Following L-T4 replacement the carotid artery baseline diameter increased by 7.1% and CIMT decreased by a mean value of 13%, while brachial artery diameter increased basally by 12.5% and following endothelium-dependent vasodilatation by 17.5% (P < 0.05). However, the increment following reactive hyperaemia did not differ before or following L-T4 replacement. CONCLUSION: Normalization of

  9. Promotor polymorphisms in leukotriene C4 synthase and risk of ischemic cerebrovascular disease

    DEFF Research Database (Denmark)

    Freiberg, J.J.; Tybjaerg-Hansen, A.; Sillesen, H.

    2008-01-01

    OBJECTIVE: Cysteinyl leukotrienes are involved in inflammation and possibly in early carotid atherosclerosis. We tested the hypothesis that the -444 A/C and -1072 G/A polymorphisms of the leukotriene C(4) synthase associate with risk of ischemic cerebrovascular disease. METHODS AND RESULTS: We...... genotyped 10 592 individuals from the Danish general population, the Copenhagen City Heart Study. During 24 years of follow-up, 557 individuals developed ischemic cerebrovascular disease. The allele frequency was 0.07 for -1072 A and 0.29 for -444 C. Cumulative incidence for ischemic cerebrovascular disease...... was higher for -1072 AA versus GG genotype (log-rank: P=0.002), and lower for -444 CC versus AA genotype (log-rank: P=0.008). Combined genotypes showed corresponding cumulative incidence differences (log-rank: P=0.003). Multifactorially adjusted hazard ratios for ischemic cerebrovascular disease were 2...

  10. A convenient synthesis of deuterated leukotriene A sub 4 methyl ester

    Energy Technology Data Exchange (ETDEWEB)

    Bestmann, H.J.; Roeder, T. (Erlangen-Nuernberg Univ., Erlangen (Germany, F.R.). Inst. fuer Organische Chemie); Meese, C.O. (Fischer-Bosch-Inst. fuer Klinische Pharmakologie, Stuttgart (Germany, F.R.))

    1989-11-01

    2,2,3,3-({sup 2}H{sub 4})-1-Iodopentane was prepared in four steps from propargyl alcohol and used in the C-alkylation of the THP-protected 3-butyne-1-ol. Subsequent protective group removal, semi-deuteration of the acetylenic alcohol and further transformation by known methods afforded the labelled key reagent 3,4,6,6,7,7-({sup 2}H{sub 6})-(Z)-(3-nonen-1-yl)triphenylphosphonium iodide. Wittig olefination of epoxy dienal with the ylide generated from the latter completed the convenient synthesis of hexadeuterated leukotriene A{sub 4} methyl ester. (author).

  11. Simultaneous initiation of degranulation and inhibition of leukotriene release by soman in human basophils

    Energy Technology Data Exchange (ETDEWEB)

    Meier, H.L.; Warner, J.; MacGlashan, D.W.

    1995-12-31

    Previous studies noted that the serine esterase inhibitor, soman, could induce histamine release from human basophils. To investigate the mechanisms by which soman causes histamine release (a preformed mediator), we also examined its ability to induce leukotriene release (a newly synthesized mediator) from basophils. We found that no leukotriene release followed activation with soman, while histamine release was usually greater than 70%. In addition, soman and diisopropyl-fluorophosphate were found actively to suppress low level spontaneous leukotriene release as well as ongoing leukotriene release induced by anti-IgE antibody. Soman (0.3 mM) was able to stop leukotriene release as rapidly as the calcium chelator, EDTA. In a series of control experiments, it was noted that soman did not influence the metabolism of LTC4 to LTD4 or LTE4 (for which little metabolism occurred), eliminating the possibility that reduced LTC4 release could have resulted from its enhanced metabolism. Therefore, using one compound (soman), basophils could be simultaneously activated to degranulate while having the pathway leading to leukotriene release actively suppressed. These results provide further evidence that histamine and leukotriene release are independent pathways resulting from the activation of basophils.

  12. Unexpected Modulation of Recall B and T Cell Responses after Immunization with Rotavirus-like Particles in the Presence of LT-R192G

    Directory of Open Access Journals (Sweden)

    Christelle Basset

    2010-08-01

    Full Text Available LT-R192G, a mutant of the thermolabile enterotoxin of E. coli, is a potent adjuvant of immunization. Immune responses are generally analyzed at the end of protocols including at least 2 administrations, but rarely after a prime. To investigate this point, we compared B and T cell responses in mice after one and two intrarectal immunizations with 2/6 rotavirus-like particles (2/6-VLP and LT-R192G. After a boost, we found, an unexpected lower B cell expansion measured by flow cytometry, despite a secondary antibody response. We then analyzed CD4+CD25+Foxp3+ regulatory T cells (Tregs and CD4+CD25+Foxp3− helper T cells after in vitro (restimulation of mesenteric lymph node cells with the antigen (2/6-VLP, the adjuvant (LT-R192G or both. 2/6-VLP did not activate CD4+CD25+Foxp3− nor Foxp3+ T cells from non-immunized and 2/6-VLP immunized mice, whereas they did activate both subsets from mice immunized with 2/6-VLP in the presence of adjuvant. LT-R192G dramatically decreased CD4+CD25+Foxp3+ T cells from non-immunized and 2/6-VLP immunized mice but not from mice immunized with 2/6-VLP and adjuvant. Moreover, in this case, LT-R192G increased Foxp3 expression on CD4+CD25+Foxp3+ cells, suggesting specific Treg activation during the recall. Finally, when both 2/6-VLP and LT-R192G were used for restimulation, LT-R192G clearly suppressed both 2/6-VLP-specific CD4+CD25+Foxp3− and Foxp3+ T cells. All together, these results suggest that LT-R192G exerts different effects on CD4+CD25+Foxp3+ T cells, depending on a first or a second contact. The unexpected immunomodulation observed during the recall should be considered in designing vaccination protocols.

  13. 2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism

    DEFF Research Database (Denmark)

    Nygaard, Birte

    2012-01-01

    . Results: Suggested explanations for persisting symptoms include: awareness of a chronic disease, presence of associated autoimmune diseases, thyroid autoimmunity per se, and inadequacy of L-T4 treatment to restore physiological thyroxine (T4) and triiodothyronine (T3) concentrations in serum and tissues...

  14. A possible role for cysteinyl-leukotrienes in non-ionic contrast media induced adverse reactions

    International Nuclear Information System (INIS)

    Boehm, Ingrid; Speck, Ulrich; Schild, Hans

    2005-01-01

    Purpose: To test whether mono- or dimeric X-ray contrast media (CM) may induce the de novo production of cysteinyl-leukotriens (cys-LT), that could contribute to allergic/allergy-like side effects. Materials and methods: Leukocytes from 39 patients receiving iopromide or iotrolan for routine CT-examination were analyzed for the production of cys-LT. Histamine levels were analyzed in plasma specimens. One patient with a positive history of a previous CM-reaction did not receive CM-injection. Results: Three patients of the iopromide and five of the iotrolan group showed adverse reactions. Reactors had increased cys-LT values in samples obtained before CM-injection induced by the positive control (anti-FcεRI antibodies) (6763.7 pg/ml ± 1367.3 versus 2299.8 pg/ml ± 399.2; p < 0.007). Patients with versus without CM-reaction did not differ significantly with respect to their histamine values before CM-administeration. In vitro iopromide (p < 0.0002) and iotrolan (p < 0.0008) induced significant cys-LT production as compared to IL-3 stimulation. In vivo both CM induced a significant increase 6 h after CM administration (p < 0.05). Conclusion: Our findings suggest that both CM seem to induce cys-LT production. As to whether the observed increased values in pre-dose samples of patients with as compared to those without reactions could contribute to identify high risk patients should be investigated in larger patient groups in future

  15. A possible role for cysteinyl-leukotrienes in non-ionic contrast media induced adverse reactions

    Energy Technology Data Exchange (ETDEWEB)

    Boehm, Ingrid [Department of Radiology, University of Bonn, Sigmund Freud Strasse 25, 53105 Bonn (Germany)]. E-mail: i.boehm@uni-bonn.de; Speck, Ulrich [Department of Radiology, Humboldt University (Charite) of Berlin (Germany); Schild, Hans [Department of Radiology, University of Bonn, Sigmund Freud Strasse 25, 53105 Bonn (Germany)

    2005-09-01

    Purpose: To test whether mono- or dimeric X-ray contrast media (CM) may induce the de novo production of cysteinyl-leukotriens (cys-LT), that could contribute to allergic/allergy-like side effects. Materials and methods: Leukocytes from 39 patients receiving iopromide or iotrolan for routine CT-examination were analyzed for the production of cys-LT. Histamine levels were analyzed in plasma specimens. One patient with a positive history of a previous CM-reaction did not receive CM-injection. Results: Three patients of the iopromide and five of the iotrolan group showed adverse reactions. Reactors had increased cys-LT values in samples obtained before CM-injection induced by the positive control (anti-Fc{epsilon}RI antibodies) (6763.7 pg/ml {+-} 1367.3 versus 2299.8 pg/ml {+-} 399.2; p < 0.007). Patients with versus without CM-reaction did not differ significantly with respect to their histamine values before CM-administeration. In vitro iopromide (p < 0.0002) and iotrolan (p < 0.0008) induced significant cys-LT production as compared to IL-3 stimulation. In vivo both CM induced a significant increase 6 h after CM administration (p < 0.05). Conclusion: Our findings suggest that both CM seem to induce cys-LT production. As to whether the observed increased values in pre-dose samples of patients with as compared to those without reactions could contribute to identify high risk patients should be investigated in larger patient groups in future.

  16. Influence of leukotriene gene polymorphisms on chronic rhinosinusitis

    Directory of Open Access Journals (Sweden)

    Duval Melanie

    2008-03-01

    Full Text Available Abstract Background Chronic rhinosinusitis (CRS is increasingly viewed as an inflammatory condition of the sinonasal mucosa interacting with bacteria and/or fungi. However, factors conferring susceptibility to disease remain unknown. Advances in genomics offer powerful tools to explore this disorder. The goal of this study was to evaluate the effect of single nucleotide polymorphisms (SNP on CRS in a panel of genes related to cysteinyl leukotriene metabolism. Methods Severe cases of CRS and postal code match controls were recruited prospectively. A total of 206 cases and 200 controls were available for the present study. Using a candidate gene approach, five genes related to cysteinyl leukotriene metabolism were assessed. For each gene, we selected the maximally informative set of common SNPs (tagSNPs using the European-derived (CEU HapMap dataset. These SNPs are in arachidonate 5-lipoxygenase (ALOX5, arachidonate 5-lipoxygenase-activating protein (ALOX5AP, leukotriene C4 synthase (LTC4S, cysteinyl leukotriene receptor 1 (CYSLTR1 and cysteinyl leukotriene receptor 2 (CYSLTR2 genes. Results A total of 59 SNPs were genotyped to capture the common genetic variations within these genes. Three SNPs located within the ALOX5, CYSLTR1 and ALOX5AP genes reached the nominal p-value threshold (p Conclusion While these initial results do not support that polymorphsims in genes assessed involved in the leukotriene pathways are contributing to the pathogenesis of CRS, this initial study was not powered to detect polymorphisms with relative risk of 2.0 or less, where we could expect many gene effects for complex diseases to occur. Thus, despite this lack of significant association noted in this study, we believe that validation with external populations and the use of better-powered studies in the future may allow more conclusive findings.

  17. CysLT1 receptor-induced human airway smooth muscle cells proliferation requires ROS generation, EGF receptor transactivation and ERK1/2 phosphorylation

    Directory of Open Access Journals (Sweden)

    Capra Valérie

    2006-03-01

    Full Text Available Abstract Background Cysteine-containing leukotrienes (cysteinyl-LTs are pivotal inflammatory mediators that play important roles in the pathophysiology of asthma, allergic rhinitis, and other inflammatory conditions. In particular, cysteinyl-LTs exert a variety of effects with relevance to the aetiology of asthma such as smooth muscle contraction, eosinophil recruitment, increased microvascular permeability, enhanced mucus secretion and decreased mucus transport and, finally, airway smooth muscle cells (ASMC proliferation. We used human ASMC (HASMC to identify the signal transduction pathway(s of the leukotriene D4 (LTD4-induced DNA synthesis. Methods Proliferation of primary HASMC was measured by [3H]thymidine incorporation. Phosphorylation of EGF receptor (EGF-R and ERK1/2 was assessed with a polyclonal anti-EGF-R or anti-phosphoERKl/2 monoclonal antibody. A Ras pull-down assay kit was used to evaluate Ras activation. The production of reactive oxygen species (ROS was estimated by measuring dichlorodihydrofluorescein (DCF oxidation. Results We demonstrate that in HASMC LTD4-stimulated thymidine incorporation and potentiation of EGF-induced mitogenic signaling mostly depends upon EGF-R transactivation through the stimulation of CysLT1-R. Accordingly, we found that LTD4 stimulation was able to trigger the increase of Ras-GTP and, in turn, to activate ERK1/2. We show here that EGF-R transactivation was sensitive to pertussis toxin (PTX and phosphoinositide 3-kinase (PI3K inhibitors and that it occurred independently from Src activity, despite the observation of a strong impairment of LTD4-induced DNA synthesis following Src inhibition. More interestingly, CysLT1-R stimulation increased the production of ROS and N-acetylcysteine (NAC abolished LTD4-induced EGF-R phosphorylation and thymidine incorporation. Conclusion Collectively, our data demonstrate that in HASMC LTD4 stimulation of a Gi/o coupled CysLT1-R triggers the transactivation of the EGF

  18. 4-Hydroxynonenal enhances MMP-9 production in murine macrophages via 5-lipoxygenase-mediated activation of ERK and p38 MAPK

    International Nuclear Information System (INIS)

    Lee, Seung J.; Kim, Chae E.; Yun, Mi R.; Seo, Kyo W.; Park, Hye M.; Yun, Jung W.; Shin, Hwa K.; Bae, Sun S.; Kim, Chi D.

    2010-01-01

    Exaggerated levels of 4-hydroxynonenal (HNE) and 5-lipoxygenase (5-LO) co-exist in macrophages in atherosclerotic lesions, and activated macrophages produce MMP-9 that degrades atherosclerotic plaque constituents. This study investigated the effects of HNE on MMP-9 production, and the potential role for 5-LO derivatives in MMP-9 production in murine macrophages. Stimulation of J774A.1 cells with HNE led to activation of 5-LO, as measured by leukotriene B 4 (LTB 4 ) production. This was associated with an increased production of MMP-9, which was blunted by inhibition of 5-LO with MK886, a 5-LO inhibitor or with 5-LO siRNA. A cysteinyl-LT 1 (cysLT 1 ) receptor antagonist, REV-5901 as well as a BLT 1 receptor antagonist, U-75302, also attenuated MMP-9 production induced by HNE. Furthermore, LTB 4 and cysLT (LTC 4 and LTD 4 ) enhanced MMP-9 production in macrophages, suggesting a pivotal role for 5-LO in HNE-mediated production of MMP-9. Among the MAPK pathways, LTB 4 and cysLT enhanced phosphorylation of ERK and p38 MAPK, but not JNK. Linked to these results, a p38 MAPK inhibitor as well as an ERK inhibitor blunted MMP-9 production induced by LT. Collectively, these data suggest that 5-LO-derived LT mediates HNE-induced MMP-9 production via activation of ERK and p38 MAPK pathways, consequently leading to plaque instability in atherosclerosis.

  19. The effect of n-3 fatty acids and coenzyme Q10 supplementation on neutrophil leukotrienes, mediators of inflammation resolution and myeloperoxidase in chronic kidney disease.

    Science.gov (United States)

    Barden, Anne E; Shinde, Sujata; Burke, Valerie; Puddey, Ian B; Beilin, Lawrence J; Irish, Ashley B; Watts, Gerald F; Mori, Trevor A

    2018-03-22

    Neutrophils release leukotriene (LT)B 4 and myeloperoxidase (MPO) that may be important mediators of chronic inflammation in chronic kidney disease (CKD). The n-3 fatty acids (n-3 FA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have the potential to attenuate inflammation through production of LTB 5 and the Specialized Proresolving Lipid Mediators (SPM) that promote the resolution of inflammation. In animal models, coenzyme Q10 (CoQ) also attenuates inflammation by reducing MPO and LTB 4 . This study evaluated the independent and combined effects of n-3 FA and CoQ supplementation on neutrophil leukotrienes, the pro-inflammatory eicosanoid 5-hydroxyeicosatetraenoic acid (5-HETE), SPM, and plasma MPO, in patients with CKD. In a double-blind, placebo-controlled intervention of factorial design, 85 patients with CKD were randomized to either n-3 FA (4 g), CoQ (200 mg), both supplements, or control (4 g olive oil), daily for 8 weeks. Plasma MPO and calcium ionophore-stimulated neutrophil release of LTs, 5-HETE and SPM were measured at baseline and after 8 weeks. Seventy four patients completed the intervention. n-3 FA, but not CoQ, significantly increased neutrophil LTB 5 (P n-3 FA or CoQ. Plasma MPO was significantly reduced with n-3 FA alone (P = 0.013) but not when given in combination with CoQ. n-3 FA supplementation in patients with CKD leads to increased neutrophil release of LTB 5 and several SPM, as well as a reduction in plasma MPO that may have important implications for limiting chronic inflammation. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Breath condensate levels of 8-isoprostane and leukotriene B4 after ozone inhalation are greater in sensitive versus nonsensitive subjects.

    Science.gov (United States)

    Alfaro, Mario F; Walby, William F; Adams, William C; Schelegle, Edward S

    2007-01-01

    Ozone (O3) inhalation induces pulmonary function decrements and inflammation. The present study was designed to determine if a relationship exists between O3 induced pulmonary function changes and the presence of inflammatory markers as measured in exhaled breath condensates (EBCs) obtained from O3-sensitive and nonsensitive human subjects. Eight healthy adult volunteers (4 males/4 females, age 18 to 30 years) were studied, characterized as to their ozone sensitivity and placed into 2 groups (sensitive and nonsensitive) with each group having 2 males and 2 females. Subjects completed a 20-minute EBC collection and pulmonary function test (PFT) prior to a single 60-minute bout of cycle ergometer exercise (V(E) = 50-55 L/min) while breathing filtered air (FA) or 0.35 ppm O3. Subjective symptom scores (SSSs) were collected at 6, 20, 40, and 60 minutes during exposure. An immediate postexposure PFT was performed followed by an EBC collection. Subjective symptom scores, EBCs, and PFTs were collected at 1, 4 and 8 hours post exposure. EBCs were analyzed for prostaglandin E2 (PGE2), leukotriene B4 (LTB4), 8-isoprostane, and total nitric oxide (NO) metabolites (nitrate + nitrite content). Sensitive subjects, breathing O3, had significantly greater functional decrements in PFTs, increased SSSs, and increased rapid shallow breathing as well as elevated levels of 8-isoprostane and LTB4 in EBCs compared to those breathing FA. In addition, there were significant increases in nitrate + nitrite content in both sensitive and nonsensitive subjects breathing O3 compared to FA. These results indicate that sensitive subjects have elevated arachidonic acid metabolites in EBCs compared to nonsensitive subjects after O3 inhalation.

  1. MAC-1 Glycoprotein Family mediates adherence of neutrophils to endothelial cells stimulated by leukotriene B/sub 4/ and platelet activating factor

    Energy Technology Data Exchange (ETDEWEB)

    Tonnesen, M.G.; Anderson, D.C.; Springer, T.A.; Knedler, A.; Avdi, N.; Henson, P.M.

    1986-03-01

    The process of neutrophil (N) adhesion to and migration through endothelium (EC), an early event in the induction of the acute inflammatory response, has been attributed to the generation of extravascular chemoattractant peptides and lipids. Although both leukotriene B/sub 4/ (LTB/sub 4/) and platelet activating factor (PAF) enhance N adherence to EC, the mechanisms involved in this interaction are still not completely understood. Since the MAC-1 Glycoprotein (GP) Family has recently been shown to be required for a variety of adherence-dependent functions of stimulated N, the authors questioned whether these adherence-associated GP might be involved in N adherence to EC stimulated by LTB/sub 4/ or PAF. Using a microtiter adherence assay with /sup 111/In labeled N, they assessed the ability of N from patients with MAC-1, LFA-1 Deficiency to adhere to monolayers of human omental microvascular or umbilical vein EC as well as to serum-coated plastic. Patient N exhibited markedly diminished adherence in response to LTB/sub 4/ or PAF compared to normal controls. LTB/sub 4/ and PAF enhanced expression of the MAC-1 GP Family on the surface of normal N as determined by flow cytofluorimetry using a monoclonal antibody (TS1/18) to the GP common beta subunit. In addition TS1/18 (20 ..mu..g/ml) completely inhibited N adherence stimulated by either LTB/sub 4/ (10/sup -8/M) or PAF(10/sup -11/M). Thus, the MAC-1 GP Family appears to be important in chemotactic factor regulation of N adherence to EC.

  2. Advancements in the treatment of hypothyroidism with L-T4 liquid formulation or soft gel capsule: an update.

    Science.gov (United States)

    Fallahi, Poupak; Ferrari, Silvia Martina; Ruffilli, Ilaria; Ragusa, Francesca; Biricotti, Marco; Materazzi, Gabriele; Miccoli, Paolo; Antonelli, Alessandro

    2017-05-01

    The most recent advance concerning levothyroxine (L-T4) therapy is the development of novel oral formulations: the liquid preparation, and the soft gel capsule. Areas covered: This review evaluates the most recent clinical studies about these new formulations. The liquid formulation has been shown to overcome: the food and beverages intereference with L-T4 tablets absorption, caused by food or coffee at breakfast; malabsorption induced by the increased gastric pH, resulting from atrophic gastritis, or due to proton-pump inhibitors; and malabsorption after bariatric surgery. The use of liquid L-T4 has been studied also in pregnancy, newborns and infants, suggesting a better bioequivalence than tablets. Finally, liquid L-T4 is more active than tablets in the control of thyroid-stimulating hormone (TSH) in hypothyroid patients without malabsorption, drug interference, or gastric disorders, leading to a hypothesized higher absorption of liquid L-T4 also in these patients. Few studies have evaluated soft gel L-T4 with promising results in patients with malabsorption related to coffee or gastritis. Expert opinion: Liquid L-T4 (and soft gel capsules) are more active than the tablet L-T4 in the control of TSH in hypothyroid patients with gastric disorders, malabsorption, or drug interference, but also in patients without absorption disorders.

  3. Pathophysiology of the cysteinyl leukotrienes and effects of leukotriene receptor antagonists in asthma

    DEFF Research Database (Denmark)

    Bisgaard, H

    2001-01-01

    , exudation of macromolecules and edema. The cysteinyl leukotrienes also have potent chemoattractant properties for eosinophils, causing an influx of eosinophils into the airway mucosa, which further fuels the inflammatory process. In addition, the cysteinyl leukotrienes are potent secretagogues and reduce...... and pranlukast inhibit bronchoconstriction in asthmatic patients undergoing allergen, exercise, cold air or aspirin challenge. They attenuate the hallmarks of asthmatic inflammation, including eosinophilia in the airway mucosa and peripheral blood. Moreover, exhaled nitric oxide concentrations, another correlate...

  4. Leukotriene B4 induces EMT and vimentin expression in PANC-1 pancreatic cancer cells: Involvement of BLT2 via ERK2 activation.

    Science.gov (United States)

    Kim, You Ri; Park, Mi Kyung; Kang, Gyeong Jin; Kim, Hyun Ji; Kim, Eun Ji; Byun, Hyun Jung; Lee, Moo-Yeol; Lee, Chang Hoon

    2016-12-01

    Leukotriene B 4 (LTB 4 ) is a leukocyte chemoattractant and plays a major role controlling inflammatory responses including pancreatitis. LTB 4 is known to be correlated with cancer progression. LTB 4 induces keratin phosphorylation and reorganization by activating extracellular regulated kinase (ERK) in PANC-1 pancreatic cancer cell lines. However, the role of LTB 4 in epithelial mesenchymal transition (EMT) and vimentin expression in pancreatic cancer cells is unknown. We examined whether LTB 4 induces EMT and vimentin expression by Western blot, si-RNA, and RT-PCR. LTB 4 induced morphological change, decreased E-cadherin expression and increased N-cadherin and vimentin expression. LTB4 increased migration and invasion of PANC-1 cancer cells. LTB 4 dose-dependently upregulated expression of vimentin in PANC-1 cancer cells. LTB 4 -induced vimentin expression was suppressed by LY255283 (BLT2 antagonist). Comp A, a BLT2 agonist, further increased vimentin expression. Gene silencing of BLT2 suppressed LTB 4 -or Comp A-induced vimentin expression in PANC-1 cells. The MEK inhibitor, PD98059 suppressed Comp A-induced vimentin expression. Comp A or transfection of plasmid containing BLT2 cDNA (pC BLT2 ) activated ERK, and BLT2 gene silencing suppressed Comp A-induced ERK activation. ERK2 siRNA abrogated Comp A-induced vimentin expression and ERK2 overexpression enhanced vimentin expression. One of well-known cause of ras mutation, cigarette smoke extracts increased BLT2 expression in PANC-1 cancer cells. Taken together, these results suggest that BLT2 is involved in LTB 4 -induced vimentin expression through ERK2 in PANC-1 cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Bone infected/inflamed conditions: Clinical experience with RP517, a Tc99m-leukotriene B4 receptor antagonist

    International Nuclear Information System (INIS)

    Soroa, V.; Nicolini, J.; Camin, L.; Ughetti, R.; Velasquez, M.

    2003-01-01

    Full text: Objectives: Tc 99m- RP517- is a receptor antagonist of Leukotriene B4 (LTB4) labelling predominantly neutrophils, in whole blood. The aim of this clinical trial was to obtain the best acquisition protocol and performance of this agent in detecting bone, joint and soft tissue infected / inflamed pathologies. Methods: RP517 was labelled with 15-20 mCi (555-740MBq) Tc99m per doses. Twenty-six patients studied (F 14, M 12) with range ages 19- 93, suspected of bone, joint and soft tissue infection (25) and one with fever of unknown origin (FUO). Laboratory data, anatomical images and one other scintiscan (MDP, Ga-67 or Tc99m- ciprofloxacin) were evaluated. Acquisition protocol: flow, 30 min, 1, 2, 3, 4 - 24h planar or Spect images as required. Results documented with histology, cultures or clinical follow up. Scans were classified as positive when abnormal uptake persisted in the 24h images or negative when positivity faded, or not detected in later images. Results: Labeling efficiency 86-90%. No adverse reactions encountered. Image protocol modified to a flow, 30 min, 4 and 24h images. Ten-fifteen % of in vivo leucocyte labelling at 1h. Early bile and intestinal excretion did not improve with cleansing enemas or food restrain. Late bone marrow activity is less visible than with in vitro leucocyte labeling. Only 16 patients had proven biopsies and cultures with coincident images in 8 True Positive; other 6 cases were True Negative, 2 False Negative (with positive Ga-67 and Tc99m-ciprofloxacin) and no False Positive. Sensitivity 80%, Specificity 100%. Conclusions: A kit should be produced in order to make it easily available. Pharmaceutically manipulation altering the excretion route could validate studies in abdominal infections and FUO that are now disesteemed. Protocol images must include 24h scans. Advantage of RP517 is the lack of cell labeling manipulation. Larger series must be studied to obtain statistics on joint bone and soft tissue infection

  6. A new practical method for the preparation of [3H6]-leukotrienes C4 and D4

    International Nuclear Information System (INIS)

    Belley, M.L.; Gareau, Y.; Zamboni, R.J.; Ahern, D.G.; Yang Hong

    1995-01-01

    A new method for the synthesis of highly deuterated or tritiated leukotrienes was developed. The higher reactivity of a terminal alkene compared to a 1,2-disubstituted one permitted the selective deuteration or tritiation of the diyne 14,15,19,19,20,20-hexadehydro LTC 4 troester 1. After hydrolysis, LTC 4 was obtained in 36% overall yield. An average of seven deuterium or tritium atoms was incorporated and the specific activity of the tritiated LTC 4 was greater than 180Ci/mmol. 1 was obtained from the addition of glutathione to 14,15,19,19,20,20-hexadehydro LTA 4 ethyl ester which was the product of a Wittig reaction between (3,8-nonanediyn-1-yl) triphenylphosphonium iodide and 5(S), 6(S), 7(E), 9(E) ethyl 5,6-epoxy-11-oxo-7,9-undecadienoate. (Author)

  7. Urinary Leukotriene E4 Is Associated with Renal Function but Not with Endothelial Function in Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Arnar Rafnsson

    2013-01-01

    Full Text Available Leukotrienes are inflammatory and vasoactive mediators implicated in endothelium-dependent relaxations and atherosclerosis. Urinary leukotriene E4 (U-LTE4 is a validated disease marker of asthma and increases also in diabetes and acute coronary syndromes. The aim of the present study was to evaluate the association of U-LTE4 and CRP with endothelial function. Urine samples were obtained from 30 subjects (80% males; median age 65 with type 2 diabetes of at least two years duration and a median glomerular filtration rate (eGFR of 71 (14–129 mL/min. Reactive hyperemia index (RHI was used as a measure of microvascular endothelial function, whereas macrovascular endothelial function was determined be means of flow-mediated dilatation of the brachial artery (FMD. Decreased renal function was associated with lower concentrations of U-LTE4. In addition, U-LTE4 was correlated with serum creatinine (R=−0.572; P=0.001 and eGFR (R=0.517; P=0.0036. A stepwise multiple linear regression analysis identified eGFR as an independent predictor of U-LTE4 concentrations. In conclusion, the present results did not establish an association of U-LTE4 with endothelial dysfunction. However, eGFR was an independent predictor of U-LTE4, but not CRP, in this cohort, suggesting that GFR should be considered in biomarker studies of U-LTE4.

  8. ENVIRONMENTAL TECHNOLOGY VERIFICATION REPORT LASER TOUCH AND TECHNOLOGIES, LLC LASER TOUCH MODEL LT-B512

    Science.gov (United States)

    The Environmental Technology Verification report discusses the technology and performance of Laser Touch model LT-B512 targeting device manufactured by Laser Touch and Technologies, LLC, for manual spray painting operations. The relative transfer efficiency (TE) improved an avera...

  9. The effect of the leukotriene antagonist pranlukast on pediatric acute otitis media.

    Science.gov (United States)

    Nakamura, Yoshihisa; Hamajima, Yuki; Suzuki, Motohiko; Esaki, Shinichi; Yokota, Makoto; Oshika, Masanori; Takagi, Ippei; Yasui, Keiko; Miyamoto, Naoya; Sugiyama, Kazuko; Nakayama, Meiho; Murakami, Shingo

    2016-08-01

    Conventional treatment for acute otitis media mainly targets bacteria with antibiotics, neglecting to control for mediators of inflammation. Mediators of inflammation, such as leukotrienes, have been identified in patients with acute otitis media (AOM) or subsequent secretory otitis media (SOM). They can cause functional eustachian tube dysfunction or increase mucous in the middle ear, causing persistent SOM following AOM. The objective of the present study was to evaluate whether or not administration of pranlukast, a widely used leukotriene C4, D4, and E4 antagonist, together with antibiotics could inhibit the progression to SOM. Children with AOM, who were from two to 12 years old, were randomly divided into two groups as follows: a control group in which 50 patients received antibiotic-based conventional treatment according to guidelines for treating AOM proposed by the Japan Otological Society (version 2006); and a pranlukast group, in which 52 patients were administered pranlukast for up to 28 days as well as given conventional treatment. Cases were regarded as persistent SOM when a tympanogram was type B or C2 four weeks after treatment was initiated. Two patients in the pranlukast group and 3 patients in the control group were excluded because they relapsed AOM within 28 days after initial treatment. Therefore, the analysis included 50 and 47 subjects in the pranlukast and control groups, respectively. The percentage of patients diagnosed with persistent SOM (22.0%) was significantly smaller in the pranlukast group compared with the control group (44.7%) (p = 0.018, chi-squared test). The results indicate that combined treatment of AOM with antibiotics and a leukotriene antagonist to control inflammation is useful for preventing progression to persistent SOM. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Leucocyte labeling: Preliminary clinical evaluation of RP517, the 99mTc-Leukotriene B4 receptor antagonist for infection/inflammation

    International Nuclear Information System (INIS)

    Soroa, V.E.; Velasquez, M.H.; Nicolini, J.; Ughetti, R.; Camin, L.

    2002-01-01

    99mTc- Leukotriene B4 (LTB4) is a receptor antagonist RP517 that labels predominantly neutrophils, in whole blood. This new radiopharmaceutical has been developed for imaging infection and inflammation. Aim: We conducted this clinical trial to obtain the best protocol imaging and the efficacy of this novel agent in the detection of suspected infected/inflamed patients. Materials and Methods: RP517 was labelled with 15-20 mCi (555-740 MBq) 99mTc for each patient, with a labeling efficiency of 86-95%. Nine patients studied (F 3, M 6) with ages 45-83, suspected of bone, joint and soft tissue infection (8) and one with fever of unknown origin (FUO). Laboratory, anatomical images and one other scintiscan (MDP, Gallium or 99mTc-ciprofloxacin) were used for evaluation. Acquisition protocol: flow, 30 min, 1, 2, 3, 4 - 24h planar or SPECT images if required. Results were compared to histology, cultures, the clinical derivation and follow up. Scans were classified as positive if abnormal uptake persisted through the 24h images or negative when absent pathological uptake or when positivity faded in later images. Results: No adverse reaction encountered. Image protocol modified to a flow, 30 min, 4 and 24h acquisitions. Early bladder excretion and intestinal activity requires previous cleansing enemas and food restrain. Late bone marrow activity is less visible than with in vitro leucocyte labeling. Coincident images were obtained in 3 True Positive, in 5 True Negative except in a hip prosthesis where Gallium and 99mTc-ciprofloxacin showed positivity and RP517 was False negative. Conclusions: A kit should be produced in order to make it available for Nuclear Medicine Departments. Known advantages of RP517 is the lack of in vitro cell labeling manipulation. We do not recommend investigation of FUO or abdominal pathologies. A larger series must be studied in order to be able to obtain statistics on joint bone and soft tissue infection/inflammation where this compound seems to be

  11. Leukotriene B₄-leukotriene B₄ receptor axis promotes oxazolone-induced contact dermatitis by directing skin homing of neutrophils and CD8⁺ T cells.

    Science.gov (United States)

    Lv, Jiaoyan; Zou, Linlin; Zhao, Lina; Yang, Wei; Xiong, Yingluo; Li, Bingji; He, Rui

    2015-09-01

    Leukotriene B4 (LTB4 ) is a lipid mediator that is rapidly generated in inflammatory sites, and its functional receptor, BLT1, is mostly expressed on immune cells. Contact dermatitis is a common inflammatory skin disease characterized by skin oedema and abundant inflammatory infiltrates, primarily including neutrophils and CD8(+) T cells. The role of the LTB4 -BLT1 axis in contact dermatitis remains largely unknown. In this study, we found up-regulated gene expression of 5-lipoxygenase and leukotriene A4 hydrolase, two critical enzymes for LTB4 synthesis, BLT1 and elevated LTB4 levels in skin lesions of oxazolone (OXA)-induced contact dermatitis. BLT1 deficiency or blockade of LTB4 and BLT1 by the antagonists, bestatin and U-75302, respectively, in the elicitation phase caused significant decreases in ear swelling and skin-infiltrating neutrophils and CD8(+) T cells, which was accompanied by significantly reduced skin expression of CXCL1, CXCL2, interferon-γ and interleukin-1β. Furthermore, neutrophil depletion during the elicitation phase of OXA-induced contact dermatitis also caused significant decreases in ear swelling and CD8(+) T-cell infiltration accompanied by significantly decreased LTB4 synthesis and gene expression of CXCL2, interferon-γ and interleukin-1β. Importantly, subcutaneous injection of exogenous LTB4 restored the skin infiltration of CD8(+) T cells in neutrophil-depleted mice following OXA challenge. Collectively, our results demonstrate that the LTB4 -BLT1 axis contributes to OXA-induced contact dermatitis by mediating skin recruitment of neutrophils, which are a major source of LTB4 that sequentially direct CD8(+) T-cell homing to OXA-challenged skin. Hence, LTB4 and BLT1 could be potential therapeutic targets for the treatment of contact dermatitis. © 2015 John Wiley & Sons Ltd.

  12. Selective blockade of leukotriene production by a single dose of the FPL 64170XX 0.5% enema in active ulcerative colitis

    DEFF Research Database (Denmark)

    Kjeldsen, J; Laursen, L S; Hillingsø, Jens

    1995-01-01

    5-Lipoxygenase products of arachidonic acid metabolism are thought to play a central role in the secondary amplification of the inflammatory response of several inflammatory diseases, including ulcerative colitis. FPL 64170XX is a selective inhibitor of the enzyme 5-lipoxygenase. Concentrations...... containing 0.5% of FPL 64170XX. Repeated measures analysis of leukotriene B4, after adjusting for baseline, showed a significant treatment effect (P = 0.0014). The concentration of leukotriene B4 from rectal dialysates in patients receiving the active drug dropped to 15% (95% confidence interval 5......-40%) of the placebo level in the second dialysis following administration of FPL 64170XX 0.5%. By contrast, prostaglanding E2 concentrations doubled (P = 0.0068) in patients receiving FPL 64170XX 0.5% with no change in the placebo group. These findings demonstrate that a single dose of FPL 64170XX 0.5% enema...

  13. Plant Natural Products Calycosin and Gallic Acid Synergistically Attenuate Neutrophil Infiltration and Subsequent Injury in Isoproterenol-Induced Myocardial Infarction: A Possible Role for Leukotriene B4 12-Hydroxydehydrogenase?

    Science.gov (United States)

    Cheng, Yuanyuan; Tse, Hung Fat; Le, X. Chris; Rong, Jianhui

    2015-01-01

    Leukotriene B4 12-hydroxydehydrogenase (LTB4DH) catalyzes the oxidation of proinflammatory LTB4 into less bioactive 12-oxo-LTB4. We recently discovered that LTB4DH was induced by two different natural products in combination. We previously isolated gallic acid from Radix Paeoniae through a bioactivity-guided fractionation procedure. The purpose of this study is to test the hypothesis that LTB4DH inducers may suppress neutrophil-mediated inflammation in myocardial infarction. We first isolated the active compound(s) from another plant, Radix Astragali, by the similar strategy. By evaluating LTB4DH induction, we identified calycosin and formononetin from Radix Astragali by HPLC-ESI-MS technique. We confirmed that gallic acid and commercial calycosin or formononetin could synergistically induce LTB4DH expression in HepG2 cells and human neutrophils. Moreover, calycosin and gallic acid attenuated the effects of LTB4 on the survival and chemotaxis of neutrophil cell culture. We further demonstrated that calycosin and gallic acid synergistically suppressed neutrophil infiltration and protected cardiac integrity in the isoproterenol-induced mice model of myocardial infarction. Calycosin and gallic acid dramatically suppressed isoproterenol-induced increase in myeloperoxidase (MPO) activity and malondialdehyde (MDA) level. Collectively, our results suggest that LTB4DH inducers (i.e., calycosin and gallic acid) may be a novel combined therapy for the treatment of neutrophil-mediated myocardial injury. PMID:26265982

  14. Urinary leukotriene E4 at 12 months and influencing factors

    Directory of Open Access Journals (Sweden)

    K Stencel-Gabriel

    2016-01-01

    • 3.        Department of Gynecology, Obstetrics and Oncological Gynecology, Bytom, Medical University of Silesia       Corresponding author: Krystyna Stencel-Gabriel ul. Batorego 15 41-902 Bytom   Keywords: leukotriene E4, infants, allergy, urine.   Summary Objective LTE4 is the end point of cysLTs pathway and its only stable product. Its role was discussed in asthma and AEDS. We aimed to investigate the impact of genetic and environmental factors ( sex, maternal positive family atopy history, breastfeeding, passive smoking and pet exposure . 60 newborns ( including 30 boys were enrolled in the study. Each child was examined at 12 months and urine samples for urinary LTE4 measurement were collected. All samples were processed using ACETM Enzyme Immunoassay Kit ( Cayman Chemical, Ann Arbor, MI, USA . The mean level of urinary LTE4 at 12 months was 186,99 pg/ml ( median: 159,0; CI 95%: 157,79- 221,59 . The Shapiro- Wilk test showed that the distribution of the levels of urinary LTE4 were abnormal. 12- month- old girls had higher urinary LTE4 levels than boys ( mean: 270,50 vs. 193,55 , but maternal positive atopy history, pet exposure, tobacco smoking or length of breastfeeding had no impact on urinary LTE4 excretion. Conclusions In conclusion, most of genetic or environmental factors do not change levels of urinary LTE4 in infants.

  15. Inhibitory activity of tryptanthrin on prostaglandin and leukotriene synthesis.

    Science.gov (United States)

    Danz, Henning; Stoyanova, Stefka; Thomet, Olivier A R; Simon, Hans-Uwe; Dannhardt, Gerd; Ulbrich, Holger; Hamburger, Matthias

    2002-10-01

    The indolo[2,1- b]quinazoline alkaloid tryptanthrin has previously been identified as the cyclooxygenase-2 (COX-2) inhibitory principle in the extract ZE550 prepared from the medicinal plant Isatis tinctoria (Brassicaceae). We here investigated the potential inhibitory activity of tryptanthrin and ZE550 on COX-2, COX-1 in cellular and cell-free systems. A certain degree of selectivity towards COX-2 was observed when COX-1-dependent formation of thromboxane B(2) (TxB(2)) in HEL cells and COX-2-dependent formation of 6-ketoprostaglandin F(1alpha) (6-keto-PGF(1alpha)) in Mono Mac 6 and RAW 264.7 cells were compared. Preferential inhibition of COX-2 by two orders of magnitude was found in phorbol myristate acetate (PMA) activated bovine aortic coronary endothelial cells (BAECs). Assays with purified COX isoenzymes from sheep confirmed the high selectivity towards COX-2. The leukotriene B(4) (LTB(4)) release from calcium ionophore-stimulated human granulocytes (neutrophils) was used as a model to determine 5-lipoxygenase (5-LOX) activity. Tryptanthrin and the extract ZE550 inhibited LTB(4) release in a dose dependent manner and with a potency comparable to that of the clinically used 5-LOX inhibitor zileuton.

  16. SNAP23-Dependent Surface Translocation of Leukotriene B4 (LTB4) Receptor 1 Is Essential for NOX2-Mediated Exocytotic Degranulation in Human Mast Cells Induced by Trichomonas vaginalis-Secreted LTB4.

    Science.gov (United States)

    Min, Arim; Lee, Young Ah; Kim, Kyeong Ah; El-Benna, Jamel; Shin, Myeong Heon

    2017-01-01

    Trichomonas vaginalis is a sexually transmitted parasite that causes vaginitis in women and itself secretes lipid mediator leukotriene B 4 (LTB 4 ). Mast cells are important effector cells of tissue inflammation during infection with parasites. Membrane-bridging SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complexes are critical for fusion during exocytosis. Although T. vaginalis-derived secretory products (TvSP) have been shown to induce exocytosis in mast cells, information regarding the signaling mechanisms between mast cell activation and TvSP is limited. In this study, we found that SNAP23-dependent surface trafficking of LTB 4 receptor 1 (BLT1) is required for nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2)-mediated exocytotic degranulation of mast cells induced by TvSP. First, stimulation with TvSP induced exocytotic degranulation and reactive oxygen species (ROS) generation in HMC-1 cells. Next, TvSP-induced ROS generation and exocytosis were strongly inhibited by transfection of BLT1 small interfering RNA (siRNA). TvSP induced trafficking of BLT1 from the cytosol to the plasma membrane. We also found that knockdown of SNAP23 abrogated TvSP-induced ROS generation, exocytosis, and surface trafficking of BLT1 in HMC-1 cells. By coimmunoprecipitation, there was a physical interaction between BLT1 and SNAP23 in TvSP-stimulated HMC-1 cells. Taken together, our results suggest that SNAP23-dependent surface trafficking of BLT1 is essential for exocytosis in human mast cells induced by T. vaginalis-secreted LTB 4 Our data collectively demonstrate a novel regulatory mechanism for SNAP23-dependent mast cell activation of T. vaginalis-secreted LTB 4 involving surface trafficking of BLT1. These results can help to explain how the cross talk mechanism between parasite and host can govern deliberately tissue inflammatory responses. Copyright © 2016 American Society for Microbiology.

  17. Characterization of LT-LiXO1-YNIYO2 electrodes for rechargeable lithium cells

    CSIR Research Space (South Africa)

    Gummow, RJ

    1993-12-01

    Full Text Available -spinel in character and that LT- Li0.4Co0.sNi0.102 is a defect spinel with spinel notation {Li0.s\\[:\\]0.2}sa \\[Co, 6Nio.2D0.2104. Electrochemical data.--The charge and discharge pro- files for the first four cycles of Li/LT-LiCoO2, Li... on the B sites of an A\\[B2104 spinel structure. The spinel phase is significantly more stable to lithium insertion/extraction reactions than the quasi-spinel phase. It is believed that by optimizing the processing conditions...

  18. Cloud Atlas: Rotational Modulations in the L/T Transition Brown Dwarf Companion HN Peg B

    Science.gov (United States)

    Zhou, Yifan; Apai, Daniel; Metchev, Stanimir; Lew, Ben W. P.; Schneider, Glenn; Marley, Mark S.; Karalidi, Theodora; Manjavacas, Elena; Bedin, Luigi R.; Cowan, Nicolas B.; hide

    2018-01-01

    Time-resolved observations of brown dwarfs' rotational modulations provide powerful insights into the properties of condensate clouds in ultra-cool atmospheres. Multi-wavelength light curves reveal cloud vertical structures, condensate particle sizes, and cloud morphology, which directly constrain condensate cloud and atmospheric circulation models. We report results from Hubble Space Telescope/Wide Field Camera 3 (WFC3) near-infrared G141 taken in six consecutive orbits observations of HNPeg B, an L/T transition brown dwarf companion to a G0V type star. The best-fit sine wave to the 1.1 to 1.7 micron broadband light curve has the amplitude of and period of hour. The modulation amplitude has no detectable wavelength dependence except in the 1.4 micron water absorption band, indicating that the characteristic condensate particle sizes are large (greater than 1 micron). We detect significantly (4.4 sigma) lower modulation amplitude in the 1.4 micron water absorption band, and find that HN Peg B's spectral modulation resembles those of early T type brown dwarfs. We also describe a new empirical interpolation method to remove spectral contamination from the bright host star. This method may be applied in other high-contrast time-resolved observations with WFC3.

  19. Association between the clinical classification of hypothyroidism and reduced TSH in LT4 supplemental replacement treatment for pregnancy in China.

    Science.gov (United States)

    Zhang, Lyu; Zhang, Zhaoyun; Ye, Hongying; Zhu, Xiaoming; Li, Yiming

    2016-01-01

    The study was aimed to evaluate the effects of levothyroxine (LT4) supplemental replacement treatment for pregnancy and analyze the associations between the clinical classification of hypothyroidism and reduced thyroid-stimulating hormone (TSH) in LT4 therapy. Totally, 195 pregnant women with hypothyroidism receiving routine prenatal care were enrolled. They were categorized into three groups: overt hypothyroidism (OH), subclinical hypothyroidism (SCH) with negative thyroperoxidase antibody (TPOAb), and SCH with positive TPOAb. The association between the clinical classification and reduced TSH in LT4 supplemental replacement treatment was assessed. The results indicated that reduced TSH was significantly different among the groups according to the clinical classifications (p = 0.043). The result was also significantly different between patients with OH and patients with SCH and negative TPOAb (p = 0.036). Similar result was reported for the comparison between patients with OH and patients with SCH and positive TPOAb (p = 0.016). Multiple variable analyses showed that LT4 supplementation, gestational age and the variable of clinical classifications were associated with reduced TSH independently. Our data suggested that the therapeutic effect of substitutive treatment with LT4 was significantly associated with different clinical classifications of hypothyroidism in pregnancy and the treatment should begin as soon as possible after diagnosis.

  20. Leukotriene signaling in the extinct human subspecies Homo denisovan and Homo neanderthalensis. Structural and functional comparison with Homo sapiens.

    Science.gov (United States)

    Adel, Susan; Kakularam, Kumar Reddy; Horn, Thomas; Reddanna, Pallu; Kuhn, Hartmut; Heydeck, Dagmar

    2015-01-01

    Mammalian lipoxygenases (LOXs) have been implicated in cell differentiation and in the biosynthesis of pro- and anti-inflammatory lipid mediators. The initial draft sequence of the Homo neanderthalensis genome (coverage of 1.3-fold) suggested defective leukotriene signaling in this archaic human subspecies since expression of essential proteins appeared to be corrupted. Meanwhile high quality genomic sequence data became available for two extinct human subspecies (H. neanderthalensis, Homo denisovan) and completion of the human 1000 genome project provided a comprehensive database characterizing the genetic variability of the human genome. For this study we extracted the nucleotide sequences of selected eicosanoid relevant genes (ALOX5, ALOX15, ALOX12, ALOX15B, ALOX12B, ALOXE3, COX1, COX2, LTA4H, LTC4S, ALOX5AP, CYSLTR1, CYSLTR2, BLTR1, BLTR2) from the corresponding databases. Comparison of the deduced amino acid sequences in connection with site-directed mutagenesis studies and structural modeling suggested that the major enzymes and receptors of leukotriene signaling as well as the two cyclooxygenase isoforms were fully functional in these two extinct human subspecies. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Repeated allergen exposure reduce early phase airway response and leukotriene release despite upregulation of 5-lipoxygenase pathways

    Directory of Open Access Journals (Sweden)

    Cui Zhi-Hua

    2012-03-01

    Full Text Available Abstract Background Allergen induced early phase airway response and airway plasma exudation are predominantly mediated by inflammatory mast cell mediators including histamine, cysteinyl leukotrienes (cysLTs and thromboxane A2 (TXA2. The aim of the present study was to evaluate whether repeated allergen exposure affects early phase airway response to allergen challenge. Methods A trimellitic anhydride (TMA sensitized guinea pig model was used to investigate the effects of low dose repeated allergen exposure on cholinergic airway responsiveness, early phase airway response and plasma exudation, as well as local airway production of mast cell derived cysteinyl leukotrienes and thromboxane B2 (TXB2 after allergen challenge. Results Repeated low dose allergen exposure increased cholinergic airway responsiveness. In contrast, early phase airway response and plasma exudation in response to a high-dose allergen challenge were strongly attenuated after repeated low dose allergen exposure. Inhibition of the airway response was unspecific to exposed allergen and independent of histamine receptor blocking. Furthermore, a significant reduction of cysteinyl leukotrienes and TXB2 was found in the airways of animals repeatedly exposed to a low dose allergen. However, in vitro stimulation of airway tissue from animals repeatedly exposed to a low dose allergen with arachidonic acid and calcium ionophore (A23187 induced production of cysteinyl leukotrienes and TXB2, suggesting enhanced activity of 5-lipoxygenase and cyclooxygenase pathways. Conclusions The inhibition of the early phase airway response, cysteinyl leukotriene and TXB2 production after repeated allergen exposure may result from unresponsive effector cells.

  2. A new method to evaluate anti-allergic effect of food component by measuring leukotriene B4 from a mouse mast cell line.

    Science.gov (United States)

    Takasugi, Mikako; Muta, Emi; Yamada, Koji; Arai, Hirofumi

    2018-02-01

    Leukotrienes (LTs), chemical mediators produced by mast cells, play an important role in allergic symptoms such as food allergies and hay fever. We tried to construct an evaluation method for the anti-LTB 4 activity of chemical substances using a mast cell line, PB-3c. PB-3c pre-cultured with or without arachidonic acid (AA) was stimulated by calcium ionophore (A23187) for 20 min, and LTB 4 production by the cells was determined by HPLC with UV detection. LTB 4 was not detected when PB-3c was pre-cultured without AA. On the other hand, LTB 4 production by PB-3c pre-cultured with AA was detectable by HPLC, and the optimal conditions of PB-3c for LTB 4 detection were to utilize the cells pre-cultured with 50 µM AA for 48 h. MK-886 (5-lipoxygenase inhibitor) completely inhibited LTB 4 production, but AACOCF 3 (phospholipase A 2 inhibitor) slightly increased LTB 4 production, suggesting that LTB 4 was generated from exogenous free AA through 5-lipoxygenase pathway. We applied this technique to the evaluation of the anti-LTB 4 activity of food components. PB-3c pre-cultured with 50 µM AA for 48 h was stimulated with A23187 in the presence of 50 µM soybean isoflavones (daidzin, genistin, daidzein, and genistein), equol, quercetin, or kaempferol. Genistein, equol, quercetin, and kaempferol strongly inhibited LTB 4 production without cytotoxicity. These results suggest that a new assay system using PB-3c is convenient to evaluate LTB 4 inhibition activity by food components. This method could be utilized for elucidation of the mechanisms of LTB 4 release suppression by food components such as flavonoids and the structure-activity relationship.

  3. The Saccharomyces boulardii CNCM I-745 Strain Shows Protective Effects against the B. anthracis LT Toxin

    Directory of Open Access Journals (Sweden)

    Rodolphe Pontier-Bres

    2015-10-01

    Full Text Available The probiotic yeast Saccharomyces boulardii (S. boulardii has been prescribed for the prophylaxis and treatment of several infectious diarrheal diseases. Gastrointestinal anthrax causes fatal systemic disease. In the present study, we investigated the protective effects conferred by Saccharomyces boulardii CNCM I-745 strain on polarized T84 columnar epithelial cells intoxicated by the lethal toxin (LT of Bacillus anthracis. Exposure of polarized T84 cells to LT affected cell monolayer integrity, modified the morphology of tight junctions and induced the formation of actin stress fibers. Overnight treatment of cells with S. boulardii before incubation with LT maintained the integrity of the monolayers, prevented morphological modification of tight junctions, restricted the effects of LT on actin remodeling and delayed LT-induced MEK-2 cleavage. Mechanistically, we demonstrated that in the presence of S. boulardii, the medium is depleted of both LF and PA sub-units of LT and the appearance of a cleaved form of PA. Our study highlights the potential of the S. boulardii CNCM I-745 strain as a prophylactic agent against the gastrointestinal form of anthrax.

  4. The Saccharomyces boulardii CNCM I-745 strain shows protective effects against the B. anthracis LT toxin.

    Science.gov (United States)

    Pontier-Bres, Rodolphe; Rampal, Patrick; Peyron, Jean-François; Munro, Patrick; Lemichez, Emmanuel; Czerucka, Dorota

    2015-10-30

    The probiotic yeast Saccharomyces boulardii (S. boulardii) has been prescribed for the prophylaxis and treatment of several infectious diarrheal diseases. Gastrointestinal anthrax causes fatal systemic disease. In the present study, we investigated the protective effects conferred by Saccharomyces boulardii CNCM I-745 strain on polarized T84 columnar epithelial cells intoxicated by the lethal toxin (LT) of Bacillus anthracis. Exposure of polarized T84 cells to LT affected cell monolayer integrity, modified the morphology of tight junctions and induced the formation of actin stress fibers. Overnight treatment of cells with S. boulardii before incubation with LT maintained the integrity of the monolayers, prevented morphological modification of tight junctions, restricted the effects of LT on actin remodeling and delayed LT-induced MEK-2 cleavage. Mechanistically, we demonstrated that in the presence of S. boulardii, the medium is depleted of both LF and PA sub-units of LT and the appearance of a cleaved form of PA. Our study highlights the potential of the S. boulardii CNCM I-745 strain as a prophylactic agent against the gastrointestinal form of anthrax.

  5. Leukotriene B4 catabolism: quantitation of leukotriene B4 and its omega-oxidation products by reversed-phase high-performance liquid chromatography.

    Science.gov (United States)

    Shak, S

    1987-01-01

    LTB4 and its omega-oxidation products may be rapidly, sensitively, and specifically quantitated by the methods of solid-phase extraction and reversed-phase high-performance liquid chromatography (HPLC), which are described in this chapter. Although other techniques, such as radioimmunoassay or gas chromatography-mass spectrometry, may be utilized for quantitative analysis of the lipoxygenase products of arachidonic acid, only the technique of reversed-phase HPLC can quantitate as many as 10 metabolites in a single analysis, without prior derivatization. In this chapter, we also reviewed the chromatographic theory which we utilized in order to optimize reversed-phase HPLC analysis of LTB4 and its omega-oxidation products. With this information and a gradient HPLC system, it is possible for any investigator to develop a powerful assay for the potent inflammatory mediator, LTB4, or for any other lipoxygenase product of arachidonic acid.

  6. Cloud Atlas: Rotational Modulations in the L/T Transition Brown Dwarf Companion HN Peg B

    Science.gov (United States)

    Zhou, Yifan; Apai, Dániel; Metchev, Stanimir; Lew, Ben W. P.; Schneider, Glenn; Marley, Mark S.; Karalidi, Theodora; Manjavacas, Elena; Bedin, Luigi R.; Cowan, Nicolas B.; Miles-Páez, Paulo A.; Lowrance, Patrick J.; Radigan, Jacqueline; Burgasser, Adam J.

    2018-03-01

    Time-resolved observations of brown dwarfs’ rotational modulations provide powerful insights into the properties of condensate clouds in ultra-cool atmospheres. Multi-wavelength light curves reveal cloud vertical structures, condensate particle sizes, and cloud morphology, which directly constrain condensate cloud and atmospheric circulation models. We report results from Hubble Space Telescope/Wide Field Camera 3 near-infrared G141 taken in six consecutive orbits observations of HN Peg B, an L/T transition brown dwarf companion to a G0V type star. The best-fit sine wave to the 1.1–1.7 μm broadband light curve has an amplitude of 1.206% ± 0.025% and period of 15.4 ± 0.5 hr. The modulation amplitude has no detectable wavelength dependence except in the 1.4 μm water absorption band, indicating that the characteristic condensate particle sizes are large (>1 μm). We detect significantly (4.4σ) lower modulation amplitude in the 1.4 μm water absorption band and find that HN Peg B’s spectral modulation resembles those of early T type brown dwarfs. We also describe a new empirical interpolation method to remove spectral contamination from the bright host star. This method may be applied in other high-contrast time-resolved observations with WFC3.

  7. Analysis of Exhaled Leukotrienes in Nonasthmatic Adult Patients with Seasonal Allergic Rhinitis

    Czech Academy of Sciences Publication Activity Database

    Čáp, P.; Pehal, F.; Malý, Marek; Chládek, J.

    2005-01-01

    Roč. 60, č. 2 (2005), s. 171-176 ISSN 0105-4538 Source of funding: V - iné verejné zdroje Keywords : allergic rhinitis * asthma * breath condensate * gas-chromatography/mass spectrometry analysis * leukotrienes Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 4.120, year: 2005

  8. Development and preclinical evaluation of safety and immunogenicity of an oral ETEC vaccine containing inactivated E. coli bacteria overexpressing colonization factors CFA/I, CS3, CS5 and CS6 combined with a hybrid LT/CT B subunit antigen, administered alone and together with dmLT adjuvant.

    Science.gov (United States)

    Holmgren, J; Bourgeois, L; Carlin, N; Clements, J; Gustafsson, B; Lundgren, A; Nygren, E; Tobias, J; Walker, R; Svennerholm, A-M

    2013-05-07

    A first-generation oral inactivated whole-cell enterotoxigenic Escherichia coli (ETEC) vaccine, comprising formalin-killed ETEC bacteria expressing different colonization factor (CF) antigens combined with cholera toxin B subunit (CTB), when tested in phase III studies did not significantly reduce overall (generally mild) ETEC diarrhea in travelers or children although it reduced more severe ETEC diarrhea in travelers by almost 80%. We have now developed a novel more immunogenic ETEC vaccine based on recombinant non-toxigenic E. coli strains engineered to express increased amounts of CF antigens, including CS6 as well as an ETEC-based B subunit protein (LCTBA), and the optional combination with a nontoxic double-mutant heat-labile toxin (LT) molecule (dmLT) as an adjuvant. Two test vaccines were prepared under GMP: (1) A prototype E. coli CFA/I-only formalin-killed whole-cell+LCTBA vaccine, and (2) A "complete" inactivated multivalent ETEC-CF (CFA/I, CS3, CS5 and CS6 antigens) whole-cell+LCTBA vaccine. These vaccines, when given intragastrically alone or together with dmLT in mice, were well tolerated and induced strong intestinal-mucosal IgA antibody responses as well as serum IgG and IgA responses to each of the vaccine CF antigens as well as to LT B subunit (LTB). Both mucosal and serum responses were further enhanced (adjuvanted) when the vaccines were co-administered with dmLT. We conclude that the new multivalent oral ETEC vaccine, both alone and especially in combination with the dmLT adjuvant, shows great promise for further testing in humans. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Leukotriene-mediated neuroinflammation, toxic brain damage, and neurodegeneration in acute methanol poisoning

    Czech Academy of Sciences Publication Activity Database

    Zakharov, S.; Kotíková, K.; Nurieva, O.; Hlušička, J.; Kačer, P.; Urban, P.; Vaněčková, M.; Seidl, Z.; Diblík, P.; Kuthan, P.; Navrátil, Tomáš; Pelclová, D.

    2017-01-01

    Roč. 55, č. 4 (2017), s. 249-259 ISSN 1556-3650 Institutional support: RVO:61388955 Keywords : brain damage * leukotrienes * methanol poisoning * Neuroinflammation * nontraumatic brain injury * sequelae of poisoning Subject RIV: CG - Electrochemistry OBOR OECD: Electrochemistry (dry cells, batteries, fuel cells, corrosion metals, electrolysis) Impact factor: 3.677, year: 2016

  10. Leukotriene B4 receptors on guinea pig alveolar eosinophils

    International Nuclear Information System (INIS)

    Maghni, K.; de Brum-Fernandes, A.J.; Foeldes-Filep, E.G.; Gaudry, M.; Borgeat, P.; Sirois, P.

    1991-01-01

    The existence of receptors for LTB4 on highly purified guinea pig alveolar eosinophils was investigated. Massive infiltration of eosinophils in alveolar spaces was induced in guinea pigs by i.v. injections of Sephadex beads G50 (16 mg/kg). Alveolar eosinophils (50 x 10(6) cells) were purified to approximately 98% by Percoll continuous density gradient centrifugation. The binding studies indicated that alveolar eosinophils bind LTB4 in a saturable, reversible and specific manner. Scatchard analysis indicated the existence of high-affinity binding sites (Kd1 = 1.00 ± 0.22 nM; Bmax1 = 966 ± 266 sites/cell) and low-affinity binding sites (Kd2 = 62.5 ± 8.9 nM; Bmax2 = 5557 ± 757 sites/cell). The metabolism of LTB4 by alveolar eosinophils in binding conditions was assessed by RP-HPLC and no significant degradation of [3H]LTB4 was observed. LTB4 dose-dependently stimulated eosinophil migration in both chemokinesis and chemotaxis assays with an EC50 value of 1.30 ± 0.14 and 18.14 ± 1.57 nM, respectively. LTB4 caused a dose-dependent increase in the production of superoxide anion with an apparent EC50 value of 50 x 10(-9) M in the authors experimental conditions. LTB4 also induced a dose-dependent increase in the generation of TxA2 with an EC50 value of 46.2 x 10(-9) M. Taken together, their results demonstrated that guinea pig alveolar eosinophils express two classes of specific receptors for LTB4. The high-affinity binding sites seem associated to chemokinesis and chemotaxis whereas the low-affinity binding sites seem associated to superoxide anion production and generation of TxA2. The existence of LTB4 receptors in eosinophils could explain the presence of these cells in hypersensitivity reactions

  11. A geranyl acetophenone targeting cysteinyl leukotriene synthesis prevents allergic airway inflammation in ovalbumin-sensitized mice

    International Nuclear Information System (INIS)

    Ismail, Norazren; Jambari, Nuzul Nurahya; Zareen, Seema; Akhtar, Mohamad Nadeem; Shaari, Khozirah; Zamri-Saad, Mohamad; Tham, Chau Ling; Sulaiman, Mohd Roslan; Lajis, Nordin Hj; Israf, Daud Ahmad

    2012-01-01

    Asthma is associated with increased pulmonary inflammation and airway hyperresponsiveness. The current use of corticosteroids in the management of asthma has recently raised issues regarding safety and lack of responsiveness in 5–10% of asthmatic individuals. The aim of the present study was to investigate the therapeutic effect of a non-steroidal small molecule that has cysteinyl leukotriene (cysLT) inhibitory activity, upon attenuation of allergic lung inflammation in an acute murine model. Mice were sensitized with ovalbumin (OVA) and treated with several intraperitoneal doses (100, 20, 2 and 0.2 mg/kg) of 2,4,6,-trihydroxy-3-geranylacetophenone (tHGA). Bronchoalveolar lavage was performed, blood and lung samples were obtained and respiratory function was measured. OVA sensitization increased pulmonary inflammation and pulmonary allergic inflammation was significantly reduced at doses of 100, 20 and 2 mg/kg with no effect at the lowest dose of 0.2 mg/kg. The beneficial effects in the lung were associated with reduced eosinophilic infiltration and reduced secretion of Th2 cytokines and cysLTs. Peripheral blood reduction of total IgE was also a prominent feature. Treatment with tHGA significantly attenuated altered airway hyperresponsiveness as measured by the enhanced pause (Penh) response to incremental doses of methacholine. These data demonstrate that tHGA, a synthetic non-steroidal small molecule, can prevent acute allergic inflammation. This proof of concept opens further avenues of research and development of tHGA as an additional option to the current armamentarium of anti-asthma therapeutics. -- Highlights: ► Safer and effective anti-asthmatic drugs are in great demand. ► tHGA is a new 5-LO/cysLT inhibitor that inhibits allergic asthma in mice. ► tHGA is a natural compound that can be synthesized. ► Doses as low as 2 mg/kg alleviate lung pathology in experimental asthma. ► tHGA is a potential drug lead for the treatment of allergic asthma.

  12. Impact of botanical oils on polyunsaturated fatty acid metabolism and leukotriene generation in mild asthmatics

    Science.gov (United States)

    2013-01-01

    Background Dietary supplementation with botanical oils that contain n-6 and n-3 eighteen carbon chain (18C)-PUFA such as γ linolenic acid (GLA, 18:3n-6), stearidonic acid (SDA, 18:4n-3) and α linolenic acid (ALA, 18:3n-3) have been shown to impact PUFA metabolism, alter inflammatory processes including arachidonic acid (AA) metabolism and improve inflammatory disorders. Methods The diet of mild asthmatics patients was supplemented for three weeks with varying doses of two botanical seed oils (borage oil [Borago officinalis, BO] and echium seed oil [Echium plantagineum; EO]) that contain SDA, ALA and GLA. A three week wash out period followed. The impact of these dietary manipulations was evaluated for several biochemical endpoints, including in vivo PUFA metabolism and ex vivo leukotriene generation from stimulated leukocytes. Results Supplementation with several EO/BO combinations increased circulating 20–22 carbon (20–22C) PUFAs, including eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and dihommo-gammalinolenic acid (DGLA), which have been shown to inhibit AA metabolism and inflammation without impacting circulating AA levels. BO/EO combinations also inhibited ex vivo leukotriene generation with some combinations attenuating cysteinyl leukotriene generation in stimulated basophils by >50% and in stimulated neutrophils by >35%. Conclusions This study shows that dietary supplementation with BO/EO alters 20–22C PUFA levels and attenuates leukotriene production in a manner consistent with a reduction in inflammation. PMID:24088297

  13. Bloqueio do receptor de leucotrieno CysLT1 em pacientes com fenômeno de Raynaud: evidência capilaroscópica do papel do leucotrieno CysLT1 receptor inhibition in patients with Raynaud's phenomenon: capillaroscopic evidence of the role of leukotriene

    Directory of Open Access Journals (Sweden)

    Mario Newton Leitão de Azevedo

    2012-02-01

    Full Text Available OBJETIVO: Avaliar a ação do medicamento inibidor do receptor de leucotrieno CysLT1 (montelucaste nas alterações vasculares das mãos em pacientes com fenômeno de Raynaud. MÉTODOS: Foram selecionadas pacientes com fenômeno de Raynaud secundário à doença inflamatória do tecido conjuntivo, excluindo tabagismo, hipertensão arterial e diabetes mellitus. As pacientes mantiveram a medicação prévia e iniciaram o uso de montelucaste 10 mg/dia por 60 dias. Foi realizada capilaroscopia periungueal dos dedos das mãos antes do uso da medicação e após 30 e 60 dias. A análise estatística foi feita por meio de porcentagem, média, desvio-padrão e teste exato de Fisher, com intervalo de confiança de 95%. RESULTADOS: Foram estudadas cinco pacientes mulheres, brancas, com fenômeno de Raynaud secundário a doenças do tecido conjuntivo, das quais três apresentavam esclerodermia e duas apresentavam doença mista do tecido conjuntivo. A média de idade foi de 42,4 ± 12,4 anos, e a média de tempo de doença foi de 9,6 ± 4,8 anos. As pacientes estavam em uso de até 20 mg/dia de prednisona (pacientes com doença mista do tecido conjuntivo, nifedipina, pentoxifilina. As medicações foram mantidas. Após o uso de inibidor de receptor de leucotrieno por dois meses, o controle com capilaroscopia ungueal demonstrou diminuição do edema e da palidez e normalização do número, tamanho e distribuição dos capilares. CONCLUSÃO: O uso do montelucaste modificou as alterações capilares observadas na capilaroscopia periungueal de pacientes com fenômeno de RaynaudOBJECTIVE: To assess the effect of the leukotriene receptor inhibitor (montelukast on vascular alterations in fingers of patients with Raynaud's phenomenon. METHODS: Patients with Raynaud's phenomenon of the hands secondary to inflammatory connective tissue disease were selected, and those with the following characteristics were excluded: smokers, arterial hypertension, and diabetes

  14. Leukotrienes and 8-isoprostane in exhaled breath condensate in bronchoprovocation tests with occupational allergens

    Czech Academy of Sciences Publication Activity Database

    Klusáčková, P.; Lebedová, J.; Kačer, P.; Kuzma, Marek; Brabec, Marek; Pelclová, D.; Fenclová, Z.; Navrátil, Tomáš

    2008-01-01

    Roč. 78, 4-5 (2008), s. 281-292 ISSN 0952-3278 Institutional research plan: CEZ:AV0Z50200510; CEZ:AV0Z10300504; CEZ:AV0Z40400503 Keywords : occupational allergens * leukotrienes * 8-isoprostane Subject RIV: CC - Organic Chemistry Impact factor: 1.366, year: 2008

  15. Lower leukotriene C4 levels in bronchoalveolar lavage fluid of asthmatic subjects after 2.5 years of inhaled corticosteroid therapy

    Directory of Open Access Journals (Sweden)

    Y. Oosterhoff

    1995-01-01

    Full Text Available Long-term treatment with inhaled corticosteroids has been shown to result in improvement of symptoms and lung function in subjects with asthma. Arachidonic acid (AA metabolites are thought to play a role in the pathophysiology of asthma. It was assessed whether differences could be found in bronchoalveolar lavage (BAL AA metabolite levels between subjects with asthma who were treated for 2.5 years with inhaled bronchodilators alone or in combination with inhaled corticosteroids. Prostaglandin (PGD2, PGF2α, 6-keto-PGF1α, thromboxane B2, leukotriene (LTC4 and LTB4 levels and cell numbers were assessed in BAL fluid from 22 non-smoking asthmatic subjects. They were participating in a randomized, double-blind multicentre drug trial over a period of 2.5 years. Results of the group treated with inhaled corticosteroids (CS+: beclomethasone 200 μg four times daily were compared with the other group (CS− which was treated with either ipratropium bromide (40 μg four times daily or placebo. BAL LTC4 levels of asthmatic subjects were significantly lower after 2.5 years inhaled corticosteroid therapy (CS+, 9(1–17 pg/ml vs. CS−, 16(6-53 pg/ml; p = 0.01. The same trend was observed for the PGD2 levels. The results suggest that inhaled corticosteroids may exert their beneficial effect on lung function via a mechanism in which inhibition of LTC4 synthesis in the airways is involved.

  16. Measurement of tumor necrosis factor-α, leukotriene B4, and interleukin 8 in the exhaled breath condensate in patients with acute exacerbations of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Fanny WS Ko

    2008-12-01

    Full Text Available Fanny WS Ko1, Ting-Fan Leung2, Gary WK Wong2, Jenny Ngai1, Kin W To1, Susanna Ng1, David SC Hui11Department of Medicine and Therapeutics; 2Department of Pediatrics, The Chinese University of Hong Kong, Hong KongBackground: Assessment of airway inflammation in the clinical course of acute exacerbations of chronic obstructive pulmonary disease (AECOPD may advance our understanding of the pathogenesis and treatment.Objectives: To assess airway inflammation in patients during the course of AECOPD by serial analyses of their exhaled breath condensates (EBC.Methods: Twenty-six patients with AECOPD (22 males, mean[SD] percentage predicted forced expiratory volume in one second (FEV1 44.8 [14.3], 11 with stable COPD, and 14 age and sex-matched healthy controls were studied. Patients with AECOPD were treated with systemic steroid and antibiotic for 7 days. EBC was collected from each patient with AECOPD on Day 5, 14, 30, and 60 post-hospitalization using EcoScreen (VIASYS Healthcare, USA during tidal breathing over 10 minutes. Concentrations of tumor necrosis factor-α (TNF-α, leukotriene B4 (LTB4, and interleukin-8 (IL-8 were measured by enzyme-linked immunosorbent assay.Results: The median (IQR of TNF-α level on Day 5 was 5.08 (3.80–6 .32 pg/ml, which was lower than on Day 14 (5.84 [4.91–9.14] pg/ml, p = 0.017, Day 30 (6.14 [3.82–7.67] pg/ml, p = 0.045, and Day 60 (5.60 [4.53–8.80] pg/ml, p = 0.009. On Day 60, subjects receiving inhaled corticosteroid (ICS had a lower level of TNF-α than those who were not (4.82 [4.06–5.65] vs 7.66 [5.48–10.9] pg/ml, p = 0.02. EBC LTB4 level did not change significantly during recovery from AECOPD whereas IL-8 was mostly undetectable.Conclusions: EBC TNF-α level was low in patients receiving systemic steroid and antibiotic therapy for AECOPD. These findings suggest a potential role for serial EBC TNF-α for noninvasive monitoring of disease activity.Keywords: COPD, exacerbation, exhaled breath

  17. Effects of doping on ferroelectric properties and leakage current behavior of KNN-LT-LS thin films on SrTiO3 substrate

    Science.gov (United States)

    Abazari, M.; Safari, A.

    2009-05-01

    We report the effects of Ba, Ti, and Mn dopants on ferroelectric polarization and leakage current of (K0.44Na0.52Li0.04)(Nb0.84Ta0.1Sb0.06)O3 (KNN-LT-LS) thin films deposited by pulsed laser deposition. It is shown that donor dopants such as Ba2+, which increased the resistivity in bulk KNN-LT-LS, had an opposite effect in the thin film. Ti4+ as an acceptor B-site dopant reduces the leakage current by an order of magnitude, while the polarization values showed a slight degradation. Mn4+, however, was found to effectively suppress the leakage current by over two orders of magnitude while enhancing the polarization, with 15 and 23 μC/cm2 remanent and saturated polarization, whose values are ˜70% and 82% of the reported values for bulk composition. This phenomenon has been associated with the dual effect of Mn4+ in KNN-LT-LS thin film, by substituting both A- and B-site cations. A detailed description on how each dopant affects the concentrations of vacancies in the lattice is presented. Mn-doped KNN-LT-LS thin films are shown to be a promising candidate for lead-free thin films and applications.

  18. Hypothyroid Patients Encoding Combined MCT10 and DIO2 Gene Polymorphisms May Prefer L-T3 + L-T4 Combination Treatment - Data Using a Blind, Randomized, Clinical Study

    DEFF Research Database (Denmark)

    Carlé, Allan; Faber, Jens; Steffensen, Rudi

    2017-01-01

    on the cellular membrane transport-facilitating monocarboxylate transporter (MCT10) gene (rs17606253), and asked in which of the 2 treatment periods patients felt better (i.e., which treatment was preferred). RESULTS: 27 out of 45 patients (60%) preferred the combination therapy. Two polymorphisms (rs225014 (DIO2......, Thr92Ala) and rs17606253 (MCT10)) were combined yielding 3 groups: none vs. 1 of 2 vs. both SNPs present, and 42 vs. 63 vs. 100% of our patients in the 3 groups preferred the combined treatment (Jongheere-Terpstra trend test, p = 0.009). CONCLUSION: The present study indicates that the combination...... of polymorphisms in DIO2 (rs225014) and MCT10 (rs17606253) enhances hypothyroid patients' preference for L-T4 + L-T3 replacement therapy. In the future, combination therapy may be restricted or may be even recommended to individuals harbouring certain polymorphisms....

  19. Staphylococcus aureus and influenza A virus stimulate human bronchoalveolar cells to release histamine and leukotrienes

    DEFF Research Database (Denmark)

    Clementsen, P; Bisgaard, H; Pedersen, M

    1989-01-01

    persons were stimulated with Staph. aureus no release of leukotriene C4 was found. The mediator release caused by bacteria and virus might be of importance for the exacerbation of bronchial asthma in upper respiratory tract infections, since histamine is assumed to increase the epithelial permeability...

  20. The IL1B-511 Polymorphism (rs16944 AA Genotype) Is Increased in Aspirin-Exacerbated Respiratory Disease in Mexican Population

    OpenAIRE

    Falf?n-Valencia, Ramc?s; Pav?n-Romero, Gandhi F.; Camarena, Angel; Garc?a, Mar?a de la Luz; Galicia-Negrete, Gustavo; Negrete-Garc?a, Mar?a Cristina; Teran, Luis Manuel

    2011-01-01

    Aspirin exacerbated respiratory disease (AERD) is characterized by chronic hyperplastic rhinosinusitis, nasal polyposis, asthma, and aspirin sensitivity. The mechanisms which produce these manifestations of intolerance are not fully defined, current research focuses on cyclooxygenase 1 (COX-1) inhibition, metabolism of arachidonic acid, and the COX pathway to the lipoxygenase (LO) route, inducing increased synthesis of leukotrienes (LT). The biological plausibility of this model has led to th...

  1. Non-genomic action of beclomethasone dipropionate on bronchoconstriction caused by leukotriene C4 in precision cut lung slices in the horse

    Directory of Open Access Journals (Sweden)

    Fugazzola Maria

    2012-09-01

    Full Text Available Abstract Background Glucocorticoids have been proven to be effective in the therapy of recurrent airway obstruction (RAO in horses via systemic as well as local (inhalative administration. Elective analysis of the effects of this drug on bronchoconstriction in viable lung tissue offers an insight into the mechanism of action of the inflammatory cascade occurring during RAO which is still unclear. The mechanism of action of steroids in treatment of RAO is thought to be induced through classical genomic pathways. We aimed at electively studying the effects of the glucocorticoid beclomethasone dipropionate on equine precision-cut lung slices (PCLS. PCLS were used to analyze ex-vivo effects of beclomethasone on inhibiting bronchoconstriction in the horse. The inhibiting effect was measured through instillation of a known mediator of inflammation and bronchoconstriction, leukotriene C4. For this, the accessory lobes of 13 horses subjected to euthanasia for reasons unrelated to the respiratory apparatus were used to obtain viable lung slices. Results After 30 minutes of PCLS incubation, beclomethasone showed to significantly inhibit the contraction of the bronchioles after instillation with leukotriene C4. The EC50 values of the two contraction curves (LTC4 with and without BDP differed significantly from each other (p = 0.002. The possibility of a non-genomic rapid mechanism of action seems likely since transcriptional activities require a longer lag period. Conclusions In human neuroendocrinology, high levels of glucocorticoids have been proven to function via a non-genomic mechanism of membrane receptors. The concentration of beclomethasone used on the lung slices in our study can be considered as high. This allows speculation about similar rapid non-genomic mechanisms of high-dosage inhaled glucocorticoids in the lower airways of horses. However, further assessment on a molecular basis is needed to confirm this.

  2. Implementation of LT codes based on chaos

    International Nuclear Information System (INIS)

    Zhou Qian; Li Liang; Chen Zengqiang; Zhao Jiaxiang

    2008-01-01

    Fountain codes provide an efficient way to transfer information over erasure channels like the Internet. LT codes are the first codes fully realizing the digital fountain concept. They are asymptotically optimal rateless erasure codes with highly efficient encoding and decoding algorithms. In theory, for each encoding symbol of LT codes, its degree is randomly chosen according to a predetermined degree distribution, and its neighbours used to generate that encoding symbol are chosen uniformly at random. Practical implementation of LT codes usually realizes the randomness through pseudo-randomness number generator like linear congruential method. This paper applies the pseudo-randomness of chaotic sequence in the implementation of LT codes. Two Kent chaotic maps are used to determine the degree and neighbour(s) of each encoding symbol. It is shown that the implemented LT codes based on chaos perform better than the LT codes implemented by the traditional pseudo-randomness number generator. (general)

  3. Exercise-induced bronchoconstriction: The effects of montelukast, a leukotriene receptor antagonist

    Directory of Open Access Journals (Sweden)

    James P Kemp

    2009-11-01

    Full Text Available James P KempClinical Professor of Pediatrics, Division of Immunology and Allergy, University of California School of Medicine, San Diego, CA, USAAbstract: Exercise-induced bronchoconstriction (EIB is very common in both patients with asthma and those who are otherwise thought to be normal. The intensity of exercise as well as the type of exercise is important in producing symptoms. This may make some types of exercise such as swimming more suitable and extended running more difficult for patients with this condition. A better understanding of EIB will allow the physician to direct the patient towards a type of exercise and medications that can result in a more active lifestyle without the same concern for resulting symptoms. This is especially important for schoolchildren who are usually enrolled in physical education classes and elite athletes who may desire to participate in competitive sports. Fortunately several medications (short- and long-acting β2-agonists, cromolyn, nedocromil, inhaled corticosteroids, and more recently leukotriene modifiers have been shown to be effective in preventing or attenuating the effects of exercise in many patients. In addition, inhaled β2-agonists have been shown to quickly reverse the airway obstruction that develops in patients and continue to be the reliever medications of choice. Inhaled corticosteroids are increasingly being recommended as regular therapy now that the role of inflammation and airway injury has been identified in EIB. With the discovery that there is a release of mediators such as histamine and leukotrienes from cells in the airway following exercise with resulting airway obstruction in susceptible individuals, interest has turned to attenuating their effects with mediator antagonists especially those that block the effects of leukotrienes. Studies with an oral leukotriene antagonist, montelukast, have shown beneficial effects in adults and children aged as young as 6 years with EIB

  4. The different requirement of L-T4 therapy in congenital athyreosis compared with adult-acquired hypothyroidism suggests a persisting thyroid hormone resistance at the hypothalamic-pituitary level.

    Science.gov (United States)

    Bagattini, Brunella; Cosmo, Caterina Di; Montanelli, Lucia; Piaggi, Paolo; Ciampi, Mariella; Agretti, Patrizia; Marco, Giuseppina De; Vitti, Paolo; Tonacchera, Massimo

    2014-11-01

    Levothyroxine (l-T4) is commonly employed to correct hormone deficiency in children with congenital hypothyroidism (CH) and in adult patients with iatrogenic hypothyroidism. To compare the daily weight-based dosage of the replacement therapy with l-T4 in athyreotic adult patients affected by CH and adult patients with thyroid nodular or cancer diseases treated by total thyroidectomy. A total of 36 adult patients (27 females and nine males) aged 18-29 years were studied; 13 patients (age: 21.5±2.1, group CH) had athyreotic CH treated with l-T4 since the first days of life. The remaining 23 patients (age: 24±2.7, group AH) had hypothyroidism after total thyroidectomy (14 patients previously affected by nodular disease and nine by thyroid carcinoma with clinical and biochemical remission). Patient weight, serum free thyroid hormones, TSH, thyroglobulin (Tg), anti-Tg, and anti-thyroperoxidase antibodies were measured. Required l-T4 dosage was evaluated. At the time of the observations, all patients presented free thyroid hormones within the normal range and TSH between 0.8 and 2 μIU/ml. Patients had undetectable Tg and anti-thyroid antibodies. The daily weight-based dosage of the replacement therapy with l-T4 to reach euthyroidism in patients of group CH was significantly higher than that in those of group AH (2.16±0.36 vs 1.73±0.24 μg/kg, Phypothyroidism, patients of group CH required a daily l-T4 dose/kg higher than group AH patients, despite higher levels of TSH. The different requirement of replacement therapy between adult patients with congenital and those with surgical athyroidism could be explained by a lack of thyroid hormones since fetal life in CH, which could determine a different set point of the hypothalamus-pituitary-thyroid axis. © 2014 European Society of Endocrinology.

  5. Blockade of leukotriene production by a single oral dose of MK-0591 in active ulcerative colitis

    DEFF Research Database (Denmark)

    Hillingsø, Jens; Kjeldsen, J; Laursen, L S

    1995-01-01

    dialysis fluid, ex vivo biosynthesis of LTB4 in whole blood, and urinary excretion of leukotriene E4 (LTE4) from 16 patients with mild to moderately active distally located ulcerative colitis were measured by use of radioimmunoassays in a double-blind, placebo-controlled parallel-design study before...... was unchanged. In whole blood, MK-0591 decreased ex vivo biosynthesis of LTB4 (p LTE4 was reduced by more than 85% (p

  6. Production of arachidonic and linoleic acid metabolites by guinea pig tracheal epithelial cells

    International Nuclear Information System (INIS)

    Oosthuizen, M.J.; Engels, F.; Van Esch, B.; Henricks, P.A.; Nijkamp, F.P.

    1990-01-01

    Pulmonary epithelial cells may be responsible for regulating airway smooth muscle function, in part by release of fatty acid-derived mediators. Incubation of isolated guinea pig tracheal epithelial cells with radiolabeled arachidonic acid (AA) leads to the production of 5- and 15-hydroxyeicosatetraenoic acid (5- and 15-HETE) and smaller amounts of leukotriene (LT) B4 and C4 and 12-hydroxyheptadecatrienoic acid (HHT). Epithelial cells also are able to release linoleic acid (LA) metabolites. Incubation with radiolabeled linoleic acid leads to the formation of 9- and 13-hydroxyoctadecadienoic acid (9- and 13-HODE). The biological significance of these mediators produced by epithelial cells is discussed

  7. Effects of cysteinyl leukotrienes and leukotriene receptor antagonists on markers of inflammation

    DEFF Research Database (Denmark)

    Sampson, Anthony P; Pizzichini, Emilio; Bisgaard, Hans

    2003-01-01

    mediators in a wide range of diseases, implying that their biological activities reach far beyond acute bronchoconstriction, the activity traditionally ascribed to them. The validity of examining sputum for "biomarkers" has improved the understanding of asthma pathophysiology, optimization of asthma......The understanding that asthma pathophysiology includes an inflammatory component has spurred the more aggressive use of anti-inflammatory therapies and created a need for effective tools to measure inflammation. Biomarkers of airway inflammation proposed are obtained by methods that are direct...... but highly invasive (bronchial biopsy, bronchoalveolar lavage), moderately direct, and less invasive (indirect sputum, exhaled air, breath condensate) or indirect and least invasive (blood, urine). Several studies described in this review have implicated the cysteinyl leukotrienes (CysLTs) as inflammatory...

  8. Molecular mechanisms of the synergy between cysteinyl-leukotrienes and receptor tyrosine kinase growth factors on human bronchial fibroblast proliferation

    Directory of Open Access Journals (Sweden)

    Hajime Yoshisue

    2006-12-01

    Full Text Available We have reported that cysteinyl-leukotrienes (cys-LTs synergise not only with epidermal growth factor (EGF but also with platelet-derived growth factor (PDGF and fibroblast growth factor (FGF to induce mitogenesis in human bronchial fibroblasts. We now describe the molecular mechanisms underlying this synergism. Mitogenesis was assessed by incorporation of [3H]thymidine into DNA and changes in protein phosphorylation by Western blotting. Surprisingly, no CysLT receptor antagonists (MK-571, montelukast, BAY u9773 prevented the synergistic mitogenesis. LTD4 did not cause phosphorylation of EGFR nor did it augment EGF-induced phosphorylation of EGFR, and the synergy between LTD4 and EGF was not blocked by the metalloproteinase inhibitor GM6001 or by an HB-EGF neutralising antibody. The EGFR-selective kinase inhibitor, AG1478, suppressed the synergy by LTD4 and EGF, but had no effect on the synergy with PDGF and FGF. While inhibitors of mitogen-activated protein kinase, phosphatidylinositol 3-kinase and protein kinase C (PKC prevented the synergy, these drugs also inhibited mitogenesis elicited by EGF alone. In contrast, pertussis toxin (PTX efficiently inhibited the potentiating effect of LTD4 on EGF-induced mitogenesis, as well as that provoked by PDGF or FGF, but had no effect on mitogenesis elicited by the growth factors alone. Whereas LTD4 alone did not augment phosphorylation of extracellular signal-regulated kinase (Erk-1/2 and Akt, it increased phosphorylation of PKC in a Gi-dependent manner. Addition of LTD4 prolonged the duration of EGF-induced phosphorylation of Erk-1/2 and Akt, both of which were sensitive to PTX. The effect of cys-LTs involves a PTX-sensitive and PKC-mediated intracellular pathway leading to sustained growth factor-dependent phosphorylation of Erk-1/2 and Akt.

  9. Bronislaw Malinowski’nin Kültür Teorisi

    OpenAIRE

    Aman, Fatih

    2014-01-01

    Bir toplumu anlamak o toplumun kültürünü anlamaya bağlıdır. Özellikle “her toplumun kendine özgü olduğu” gerçeği kültür konusunda birçok araştırmanın yapılmasını sağlamış ve kültürel araştırmaları daha da ilginç kılmıştır. Bu araştırmalardan birisi de Bronislaw Malinowski’ye aittir. O, kültürün kökeniyle ilgilenmiş, kültürün fonksiyonlarını tanımlamış, kültürel araştırma tekniklerini ilk defa bilimsel ölçütlerle ortaya koymuş ve eleştirileriyle toplamda bir kültür teorisi oluşturmuştur. Malin...

  10. Interpretation of the CABRI LT1 test with SAS4A-code analysis

    International Nuclear Information System (INIS)

    Sato, Ikken; Onoda, Yu-uichi

    2001-03-01

    In the CABRI-FAST LT1 test, simulating a ULOF (Unprotected Loss of Flow) accident of LMFBR, pin failure took place rather early during the transient. No fuel melting is expected at this failure because the energy injection was too low and a rapid gas-release-like response leading to coolant-channel voiding was observed. This channel voiding was followed by a gradual fuel breakup and axial relocation. With an aid of SAS4A analysis, interpretation of this test was performed. Although the original SAS4A model was not well fitted to this type of early pin failure, the global behavior after the pin failure was reasonably simulated with temporary modifications. Through this study, gas release behavior from the failed fuel pin and its effect on further transient were well understood. It was also demonstrated that the SAS4A code has a potential to simulate the post-failure behavior initiated by a very early pin failure provided that necessary model modification is given. (author)

  11. Endogenous secreted phospholipase A2 group X regulates cysteinyl leukotrienes synthesis by human eosinophils.

    Science.gov (United States)

    Hallstrand, Teal S; Lai, Ying; Hooper, Kathryn A; Oslund, Rob C; Altemeier, William A; Matute-Bello, Gustavo; Gelb, Michael H

    2016-01-01

    Phospholipase A2s mediate the rate-limiting step in the formation of eicosanoids such as cysteinyl leukotrienes (CysLTs). Group IVA cytosolic PLA2α (cPLA2α) is thought to be the dominant PLA2 in eosinophils; however, eosinophils also have secreted PLA2 (sPLA2) activity that has not been fully defined. To examine the expression of sPLA2 group X (sPLA2-X) in eosinophils, the participation of sPLA2-X in the formation of CysLTs, and the mechanism by which sPLA2-X initiates the synthesis of CysLTs in eosinophils. Peripheral blood eosinophils were obtained from volunteers with asthma and/or allergy. A rabbit polyclonal anti-sPLA2-X antibody identified sPLA2-X by Western blot. We used confocal microscopy to colocalize the sPLA2-X to intracellular structures. An inhibitor of sPLA2-X (ROC-0929) that does not inhibit other mammalian sPLA2s, as well as inhibitors of the mitogen-activated kinase cascade (MAPK) and cPLA2α, was used to examine the mechanism of N-formyl-methionyl-leucyl-phenylalanine (fMLP)-mediated formation of CysLT. Eosinophils express the mammalian sPLA2-X gene (PLA2G10). The sPLA2-X protein is located in the endoplasmic reticulum, golgi, and granules of eosinophils and moves to the granules and lipid bodies during fMLP-mediated activation. Selective sPLA2-X inhibition attenuated the fMLP-mediated release of arachidonic acid and CysLT formation by eosinophils. Inhibitors of p38, extracellular-signal-regulated kinases 1/2 (p44/42 MAPK), c-Jun N-terminal kinase, and cPLA2α also attenuated the fMLP-mediated formation of CysLT. The sPLA2-X inhibitor reduced the phosphorylation of p38 and extracellular-signal-regulated kinases 1/2 (p44/42 MAPK) as well as cPLA2α during cellular activation, indicating that sPLA2-X is involved in activating the MAPK cascade leading to the formation of CysLT via cPLA2α. We further demonstrate that sPLA2-X is activated before secretion from the cell during activation. Short-term priming with IL-13 and TNF/IL-1β increased the

  12. Bronchoprotection with a leukotriene receptor antagonist in asthmatic preschool children

    DEFF Research Database (Denmark)

    Bisgaard, H; Nielsen, K G

    2000-01-01

    We hypothesized that a leukotriene receptor antagonist (LTRA) could provide bronchoprotection against the cold, dry air-induced response in asthmatic preschool children. In a randomized, double-blind, placebo-controlled crossover study, we examined the effect of the specific LTRA montelukast at 5...

  13. A SEARCH FOR L/T TRANSITION DWARFS WITH PAN-STARRS1 AND WISE. II. L/T TRANSITION ATMOSPHERES AND YOUNG DISCOVERIES

    International Nuclear Information System (INIS)

    Best, William M. J.; Liu, Michael C.; Magnier, Eugene A.; Aller, Kimberly M.; Chambers, K. C.; Flewelling, H.; Hodapp, K. W.; Kaiser, N.; Tonry, J. L.; Wainscoat, R. J.; Waters, C.; Deacon, Niall R.; Redstone, Joshua; Burgett, W. S.; Draper, P.; Metcalfe, N.

    2015-01-01

    The evolution of brown dwarfs from L to T spectral types is one of the least understood aspects of the ultracool population, partly for lack of a large, well-defined, and well-characterized sample in the L/T transition. To improve the existing census, we have searched ≈28,000 deg 2 using the Pan-STARRS1 and Wide-field Infrared Survey Explorer surveys for L/T transition dwarfs within 25 pc. We present 130 ultracool dwarf discoveries with estimated distances ≈9–130 pc, including 21 that were independently discovered by other authors and 3 that were previously identified as photometric candidates. Seventy-nine of our objects have near-IR spectral types of L6–T4.5, the most L/T transition dwarfs from any search to date, and we have increased the census of L9–T1.5 objects within 25 pc by over 50%. The color distribution of our discoveries provides further evidence for the “L/T gap,” a deficit of objects with (J − K) MKO  ≈ 0.0–0.5 mag in the L/T transition, and thus reinforces the idea that the transition from cloudy to clear photospheres occurs rapidly. Among our discoveries are 31 candidate binaries based on their low-resolution spectral features. Two of these candidates are common proper motion companions to nearby main sequence stars; if confirmed as binaries, these would be rare benchmark systems with the potential to stringently test ultracool evolutionary models. Our search also serendipitously identified 23 late-M and L dwarfs with spectroscopic signs of low gravity implying youth, including 10 with vl-g or int-g gravity classifications and another 13 with indications of low gravity whose spectral types or modest spectral signal-to-noise ratio do not allow us to assign formal classifications. Finally, we identify 10 candidate members of nearby young moving groups (YMG) with spectral types L7–T4.5, including three showing spectroscopic signs of low gravity. If confirmed, any of these would be among the coolest known YMG members and would

  14. Resolution of Toll-like receptor 4-mediated acute lung injury is linked to eicosanoids and suppressor of cytokine signaling 3.

    Science.gov (United States)

    Hilberath, Jan N; Carlo, Troy; Pfeffer, Michael A; Croze, Roxanne H; Hastrup, Frantz; Levy, Bruce D

    2011-06-01

    The purpose of this study was to investigate roles for Toll-like receptor 4 (TLR4) in host responses to sterile tissue injury. Hydrochloric acid was instilled into the left mainstem bronchus of TLR4-defective (both C3H/HeJ and congenic C.C3-Tlr4(Lps-d)/J) and control mice to initiate mild, self-limited acute lung injury (ALI). Outcome measures included respiratory mechanics, barrier integrity, leukocyte accumulation, and levels of select soluble mediators. TLR4-defective mice were more resistant to ALI, with significantly decreased perturbations in lung elastance and resistance, resulting in faster resolution of these parameters [resolution interval (R(i)); ∼6 vs. 12 h]. Vascular permeability changes and oxidative stress were also decreased in injured HeJ mice. These TLR4-defective mice paradoxically displayed increased lung neutrophils [(HeJ) 24×10(3) vs. (control) 13×10(3) cells/bronchoalveolar lavage]. Proresolving mechanisms for TLR4-defective animals included decreased eicosanoid biosynthesis, including cysteinyl leukotrienes (80% mean decrease) that mediated CysLT1 receptor-dependent vascular permeability changes; and induction of lung suppressor of cytokine signaling 3 (SOCS3) expression that decreased TLR4-driven oxidative stress. Together, these findings indicate pivotal roles for TLR4 in promoting sterile ALI and suggest downstream provocative roles for cysteinyl leukotrienes and protective roles for SOCS3 in the intensity and duration of host responses to ALI.

  15. Evidence for autocrine and paracrine regulation of allergen-induced mast cell mediator release in the guinea pig airways.

    Science.gov (United States)

    Yu, Li; Liu, Qi; Canning, Brendan J

    2018-03-05

    Mast cells play an essential role in immediate type hypersensitivity reactions and in chronic allergic diseases of the airways, including asthma. Mast cell mediator release can be modulated by locally released autacoids and circulating hormones, but surprisingly little is known about the autocrine effects of mediators released upon mast cell activation. We thus set out to characterize the autocrine and paracrine effects of mast cell mediators on mast cell activation in the guinea pig airways. By direct measures of histamine, cysteinyl-leukotriene and thromboxane release and with studies of allergen-evoked contractions of airway smooth muscle, we describe a complex interplay amongst these autacoids. Notably, we observed an autocrine effect of the cysteinyl-leukotrienes acting through cysLT 1 receptors on mast cell leukotriene release. We confirmed the results of previous studies demonstrating a marked enhancement of mast cell mediator release following cyclooxygenase inhibition, but we have extended these results by showing that COX-2 derived eicosanoids inhibit cysteinyl-leukotriene release and yet are without effect on histamine release. Given the prominent role of COX-1 inhibition in aspirin-sensitive asthma, these data implicate preformed mediators stored in granules as the initial drivers of these adverse reactions. Finally, we describe the paracrine signaling cascade leading to thromboxane synthesis in the guinea pig airways following allergen challenge, which occurs indirectly, secondary to cysLT 1 receptor activation on structural cells and/ or leukocytes within the airway wall, and a COX-2 dependent synthesis of the eicosanoid. The results highlight the importance of cell-cell and autocrine interactions in regulating allergic responses in the airways. Copyright © 2017. Published by Elsevier B.V.

  16. Introducing Leo LT - the "three-headed lion"

    Index Scriptorium Estoniae

    2008-01-01

    Leedu valitsus kiitis heaks seaduseparandused, mille tulemusena saab võtta tuumajaama ehitaja, investeerimis- ja energiafirma Leo LT strateegilise tähtsusega firmade hulka. Kui parlament valitsuse ettepanekud heaks kiidab, saab riik 61,7% Leo LT ja 38,3% NDX Energija aktsiatest

  17. TEO LT hakkab kaotama atraktiivsust / Romet Kreek

    Index Scriptorium Estoniae

    Kreek, Romet, 1972-

    2011-01-01

    Autori sõnul on Leedu telekomiettevõtte TEO LT puhul raske oodata, et käive ja kasum kasvaksid, parimal juhul on need stabiilsed. Osalt on selle põhjuseks tehnoloogilised muutused, osalt suuromaniku poliitika. TEO LT I kvartali majandusnäitajatest

  18. PHARMACOGENOMICS OF PROSTAGLANDIN AND LEUKOTRIENE RECEPTORS

    Directory of Open Access Journals (Sweden)

    José Antonio Cornejo-García

    2016-09-01

    Full Text Available Individual genetic background together with environmental effects are thought to be behind many human complex diseases. A number of genetic variants, mainly single nucleotide polymorphisms (SNPs, have been shown to be associated with various pathological and inflammatory conditions, representing potential therapeutic targets. Prostaglandins (PTGs and leukotrienes (LTs are eicosanoids derived from arachidonic acid and related polyunsaturated fatty acids that participate in both normal homeostasis and inflammatory conditions. These bioactive lipid mediators are synthesised through two major multistep enzymatic pathways: PTGs by cyclooxygenase and LTs by 5-lipoxygenase. The main physiological effects of PTGs include vasodilation and vascular leakage (PTGE2; mast cell maturation, eosinophil recruitment and allergic responses (PTGD2; vascular and respiratory smooth muscle contraction (PTGF2, and inhibition of platelet aggregation (PTGI2. LTB4 is mainly involved in neutrophil recruitment, vascular leakage, and epithelial barrier function, whereas cysteinyl LTs (CysLTs (LTC4, LTD4 and LTE4 induce bronchoconstriction and neutrophil extravasation, and also participate in vascular leakage. PTGs and LTs exert their biological functions by binding to cognate receptors, which belong to the seven transmembrane, G protein-coupled receptor superfamily. SNPs in genes encoding these receptors may influence their functionality and have a role in disease susceptibility and drug treatment response. In this review we summarize SNPs in PTGs and LTs receptors and their relevance in human diseases. We also provide information on gene expression. Finally, we speculate on future directions for this topic.

  19. Isolated Subclinical Hyperthyrotropinemia in Obese Children: Does Levothyroxine (LT4 Improve Weight Reduction during Combined Behavioral Therapy?

    Directory of Open Access Journals (Sweden)

    Pawel Matusik

    2015-01-01

    Full Text Available Objective. The study aim was to analyze whether anthropometrical parameters and TSH values in obese children with isolated subclinical hypothyroidism (IsHT treated with levothyroxine (LT4 and weight reduction program differ from those managed by dietary and behavior counselling only. Material and Methods. 51 obese children with IsHT, who were treated according to the same weight reduction program, were retrospectively analyzed. They were divided into two groups: Group 1, n=26, and Group 2, n=25, without or with LT4 therapy, respectively. Changes in anthropometrical (delta BMI z-score and hormonal (delta TSH status were analyzed at the first follow-up visit. Results. In both groups significant decrease of TSH and BMI z-score values were noted. TSH normalized in 80.9% of children from Group 1 versus 90.5% from Group 2, p = NS. Delta BMI z-score was insignificantly higher in Group 1 compared to Group 2. Delta TSH was significantly related to initial TSH level in children treated by lifestyle intervention program only. Conclusions. In obese children with sHT dietary-behavioral management intervention contributed to reduction of body mass index, irrespective of levothyroxine use. This finding suggests that moderately elevated levels of TSH are a consequence rather than cause of overweight and pharmacological treatment should be avoided.

  20. Gas Chromatography/mass Spectrometry Analysis of Exhaled Leukotrienes in Asthmatic Patients

    Czech Academy of Sciences Publication Activity Database

    Čáp, P.; Chládek, J.; Pehal, F.; Malý, Marek; Petrů, V.; Barnes, P.J.; Montuschi, P.

    2004-01-01

    Roč. 59, č. 6 (2004), s. 465-470 ISSN 0040-6376 Source of funding: V - iné verejné zdroje Keywords : asthma * breath condensate * gas chromatography/mass spectrometry * leukotrienes Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 5.040, year: 2004

  1. A specific assay for leukotriene B4 in human whole blood

    DEFF Research Database (Denmark)

    Fogh, J; Poulsen, L K; Bisgaard, H

    1992-01-01

    between standard and sample dilution curves. Purification was, therefore, extended by combinations of the following steps: 1) protein precipitation, 2) lipid extractions, and 3) high-performance liquid chromatography (HPLC). One of two commercially available LTB4 standards was found to contain multiple...... components, several of which were immunoreactive in RIA. Even for the standard containing pure LTB4, interference was demonstrated by lack of parallelism between sample and standard dilution curves. Testing eight combinations of varying purification steps, we found that only a three-step purification...

  2. The anti-inflammatory effect of montelukast, a cysteinyl leukotriene receptor-1 antagonist, against estradiol-induced nonbacterial inflammation in the rat prostate.

    Science.gov (United States)

    Said, Mahmoud M; Bosland, Maarten C

    2017-02-01

    There is no standard treatment of chronic nonbacterial prostatitis in humans. The current study was aimed to investigate the effect of montelukast, an antagonist of cysteinyl leukotriene receptor-1, against estrogen-induced, nonbacterial lateral lobe-specific prostate inflammation in rats. Male Wistar rats were randomized into five groups of six rats, including sham controls (group 1) and castrated rats (group 2), whereas nonbacterial prostatitis (NBP) was induced in groups 3-5 by castration followed by a daily subcutaneous injection of estradiol (0.25 mg/kg body weight) for 30 days. The rats were left otherwise untreated (group 3) or received a daily oral administration of montelukast (1 and 10 mg/kg body weight for groups 4 and 5, respectively) from the 17th day after castration for two consecutive weeks. Compared with sham controls, induction of NBP led to a significant increase in serum leukotriene B 4 (LTB4), tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6) levels, along with a significant upregulation in the transcript level of proinflammatory molecules (nuclear factor kappa beta [NF-κβ] and inducible nitric oxide synthase [iNOS]), chemokines (monocyte chemoattractant protein-1 [MCP-1] and eotaxin), and E-selectin in the lateral prostate. Histological examination revealed intense inflammation in the prostate with leukocyte infiltration and acinar degeneration following estradiol treatment of castrated rats. Montelukast significantly suppressed the increase in serum and prostate proinflammatory mediators/chemokines expression and abolished the histologically inflammatory changes in the lateral prostate. These findings indicate that montelukast inhibits estradiol-induced NBP in a rat model through anti-inflammatory mechanisms, suggesting its future beneficial effect for the treatment of clinical chronic NBP.

  3. Comparison of results of simulation of the CONTEMPT-LT/028 and lAP-3B codes for the analysis of the internal vacuum breaker valves of the CNLV; Comparacion de resultados de simulacion de los codigos CONTEMPT-LT/028 y MAAP-3B para el analisis de las valvulas rompedoras de vacio internas de la CNLV

    Energy Technology Data Exchange (ETDEWEB)

    Ovando C, R.; Cecenas F, M. [Instituto de Investigaciones Electricas, Gerencia de Energia Nuclear, Av. Reforma 113 Col. Palmira. 62490, Cuernavaca, Morelos (Mexico); Moya C, M.M. [Comision Federal de Electricidad. Gerencia de Centrales Nucleoelectricas Disciplina de Analisis de Ingenieria. Subgerencia de Ingenieria. Carretera Veracruz-Medellin Km 7.5, Dos Bocas, Veracruz (Mexico)]. e-mail: rovando@iie.org.mx

    2006-07-01

    In the primary container of a BWR type reactor, the humid and dry wells its are communicate by means of valves designed to equal the pressure in case of a significant pressure difference exists, produced by an operative event just as the performance of an emergency system. These valves are known as internal vacuum breakers and its analysis it is made by means of the use of a code with the capacity to analyze the primary contention of the reactor. Among the codes able to carry out this analysis type there is CONTEMPT-LT/028 and MAAP-3B; however, these codes possess characteristic different respect the modeling one of the different damage mitigation systems to the contention (dews, windy, emergency systems), of the transfer of heat among the different compartments of the primary container and in the details of the civil construction. In previous works carried out with the CONTEMPT-LT/028 code, they have been carried out different cases of simulation related with the operation of the internal breaker vacuum valves. These cases include small ruptures in the main steam lines and ruptures in the recirculation knots. It was selected the case more restrictive and it was generated an equivalent scenario file for the MAAP-3B code. In this work the performance of the internal breaker vacuum valves is analyzed by means of the CONTEMPT-LT/028 and MAAP-3B codes, when using the case more restrictive consistent in a small rupture in a main steam line. The analysis of the simulations indicates that both codes produce very similar results and the found differences are explained with base in the models used by each code to obtain the answer of the main thermohydraulic variables. In general terms, MAAP-3B possesses models that adapt in a form more convenient to the prospective phenomenology for this analysis, maintaining a conservative focus. (Author)

  4. Effects of Xingbi gel on leukotriene E4 and immunoglobulin E production and nasal eosinophilia in a guinea pig model for allergic rhinitis.

    Science.gov (United States)

    Ai, Si; Zheng, Jian; Chu, Ke-Dan; Zhang, Hong-Sheng

    2015-06-01

    Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal airways.Many therapies do not have immediate effects,even which have side-effects.However,the effects of Xingbi gel for the treatment of AR was investigated. We investigated the effects of Xingbi gel on serum levels of leukotriene E4 (LTE4) and immunoglobulin E (IgE), as well as eosinophil counts in the nasal mucosa using a guinea pig model of allergic rhinitis (AR). In addition to a healthy control group without AR, guinea pigs with AR were randomly divided into untreated AR control group, low-dose Xingbi gel (0.2483 g/mL) group, high-dose Xingbi gel (0.4966 g/mL) group, and budesonide group. Compared to the healthy controls, untreated AR guinea pigs had significantly higher ethology scores, serum LTE4 and IgE levels, and nasal mucosa eosinophil counts (p guinea pigs (p production and reducing eosinophilia in the nasal mucosa.

  5. Oenothera paradoxa defatted seeds extract and its bioactive component penta-O-galloyl-β-D-glucose decreased production of reactive oxygen species and inhibited release of leukotriene B4, interleukin-8, elastase, and myeloperoxidase in human neutrophils.

    Science.gov (United States)

    Kiss, Anna K; Filipek, Agnieszka; Czerwińska, Monika; Naruszewicz, Marek

    2010-09-22

    In this study, we analyzed ex vivo the effect of an aqueous extract of Oenothera paradoxa defatted seeds on the formation of neutrophil-derived oxidants. For defining active compounds, we also tested lypophilic extract constituents such as gallic acid, (+)-catechin, ellagic acid, and penta-O-galloyl-β-D-glucose and a hydrophilic fraction containing polymeric procyanidins. The anti-inflammatory potential of the extract and compounds was tested by determining the release from activated neutrophils of elastase, myeloperoxidase, interleukin-8 (IL-8), and leukotriene B4 (LTB4), which are considered relevant for the pathogenesis of cardiovascular diseases. The extract of O. paradoxa defatted seeds displays potent antioxidant effects against both 4β-phorbol-12β-myristate-α13-acetate- and formyl-met-leu-phenylalanine-induced reactive oxygen species production in neutrophils with IC50 values around 0.2 μg/mL. All types of polyphenolics present in the extract contributed to the extract antioxidant activity. According to their IC50 values, penta-O-galloyl-β-D-glucose was the more potent constituent of the extract. In cell-free assays, we demonstrated that this effect is partially due to the scavenging of O2- and H2O2 oxygen species. The extract and especially penta-O-galloyl-β-D-glucose significantly inhibit elastase, myeloperoxidase IL-8, and LTB4 release with an IC50 for penta-O-galloyl-β-D-glucose of 17±1, 15±1, 6.5±2.5, and around 20 μM, respectively. The inhibition of penta-O-galloyl-β-D-glucose on reactive oxygen species and especially on O2- production, myeloperoxidase, and chemoattractant release may reduce the interaction of polymorphonuclear leukocyte with the vascular endothelium and by that potentially diminish the risk of progression of atherosclerosis development.

  6. Rotavirus 2/6 Viruslike Particles Administered Intranasally with Cholera Toxin, Escherichia coli Heat-Labile Toxin (LT), and LT-R192G Induce Protection from Rotavirus Challenge

    Science.gov (United States)

    O’Neal, Christine M.; Clements, John D.; Estes, Mary K.; Conner, Margaret E.

    1998-01-01

    We have shown that rotavirus 2/6 viruslike particles composed of proteins VP2 and VP6 (2/6-VLPs) administered to mice intranasally with cholera toxin (CT) induced protection from rotavirus challenge, as measured by virus shedding. Since it is unclear if CT will be approved for human use, we evaluated the adjuvanticity of Escherichia coli heat-labile toxin (LT) and LT-R192G. Mice were inoculated intranasally with 10 μg of 2/6-VLPs combined with CT, LT, or LT-R192G. All three adjuvants induced equivalent geometric mean titers of rotavirus-specific serum antibody and intestinal immunoglobulin G (IgG). Mice inoculated with 2/6-VLPs with LT produced significantly higher titers of intestinal IgA than mice given CT as the adjuvant. All mice inoculated with 2/6-VLPs mixed with LT and LT-R192G were totally protected (100%) from rotavirus challenge, while mice inoculated with 2/6-VLPs mixed with CT showed a mean 91% protection from challenge. The availability of a safe, effective mucosal adjuvant such as LT-R192G will increase the practicality of administering recombinant vaccines mucosally. PMID:9525668

  7. Characterization and Validation of the LT-SYS Copper Assay on a Roche Cobas 8000 c502 Analyzer.

    Science.gov (United States)

    Kraus, F Bernhard; Mischereit, Marlies; Eller, Christoph; Ludwig-Kraus, Beatrice

    2017-02-01

    Validation of the LT-SYS quantitative in vitro copper assay on a Roche Cobas 8000 c502 analyzer and comparison with a BIOMED assay on a Roche Cobas Mira analyzer. Imprecision and bias were quantified at different concentration levels (serum and plasma) over a 20-day period. Linearity was assessed covering a range from 4.08 µmol/L to 33.8 µmol/L. Limit of blank (LoB) and limit of detection (LoD) were established based on a total of 120 blank and low-level samples. The method comparison was based on 58 plasma samples. Within-run imprecision ranged from 0.7% to 1.2% and within-laboratory imprecision from 1.4% to 3.3%. Relative bias for the 2 serum pools with known target values was less than 2.5%. The assay did not deviate from linearity over the tested measuring range. LoB and LoD were 0.12 µmol/L and 0.23 µmol/L, respectively. The method comparison revealed an average deviation of 11.5% (2.016 µmol/L), and the linear regression fit was y = 1.464 + 0.795x. The LT-SYS copper assay characterized in this study showed a fully acceptable performance with good degrees of imprecision and bias, no deviation from linearity in the relevant measuring rangem, and very low LoB and LoD. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Yoğurt Yapımında Saf Kültürün Kullanımı

    Directory of Open Access Journals (Sweden)

    Sevda Kılıç

    2015-02-01

    Full Text Available Yoğurt, sütün L. bulgaricus ve S. thermophilus bakterilerini belirli oranlarda içeren kültürle aşılanması sonucu elde edilen bir süt mamülüdür. Yoğurt teknolojisinde yaklaşık 70 yıldır kültür kullanılmaktadır. Kültürün hazırlanmasında yararlanılan bakteriler, belirli özellikleri dikkate alınarak seçilmektedir. Daha sonra yağsız süt tozundan hazırlanan süte aşılanarak 42-44 oC’de inkübasyona bırakılmakta ve pH 4.7 olduğunda inkübasyona son verilerek çoğaltımı ve aktifleşmeleri sağlanmaktadır. Günümüzde diğer ülkelerde olduğu gibi ülkemizde de kültür kullanımı gıda maddeleri tüzüğünün 51. maddesine göre zorunlu tutulmaktadır. Ancak buna rağmen kültür, tam anlamıyla bilinmemekte veya bilinçli olarak kullanılmamaktadır. Yoğurt teknolojisinde kültür, kullanımı ile daha kaliteli yoğurt yapılmaktadır. Uzun süre tat, aroma ve yapısı bozulmadan saklanabilmekte, raf ömrü uzamaktadır. Normal sertlikte olan yoğurtta asitlik istenilen düzeyde olduğu için su salmada görülmez.

  9. Feedback in LT codes for prioritized and non-prioritized data

    DEFF Research Database (Denmark)

    Sørensen, Jesper Hemming; Popovski, Petar; Østergaard, Jan

    2012-01-01

    In this paper feedback in LT codes is investigated. The considered type of feedback is acknowledgments, where information on which symbols have been decoded is given to the transmitter. Our analysis reveals that acknowledgments has a very low potential in LT codes with standard degree distributions....... Motivated by this, we analyze the impact of acknowledgments on multi-layer LT codes. In this case, feedback proves advantageous. By using only a single feedback message, it is possible to achieve a significant performance improvement compared to traditional LT codes....

  10. Observation of High Momentum {ital {eta}}{sup {prime}} Production in {ital B} Decays

    Energy Technology Data Exchange (ETDEWEB)

    Browder, T.E.; Li, Y.; Rodriguez, J.L. [University of Hawaii at Manoa, Honolulu, Hawaii 96822 (United States); Bergfeld, T.; Eisenstein, B.I.; Ernst, J.; Gladding, G.E.; Gollin, G.D.; Hans, R.M.; Johnson, E.; Karliner, I.; Marsh, M.A.; Palmer, M.; Selen, M.; Thaler, J.J. [University of Illinois, Urbana-Champaign, Illinois 61801 (United States); Edwards, K.W.; Edwards, K.W. [the Institute of Particle Physics, Montreal, Quebec (Canada); Bellerive, A.; Bellerive, A.; Janicek, R.; Janicek, R.; MacFarlane, D.B.; MacFarlane, D.B.; Patel, P.M.; Patel, P.M. [the Institute of Particle Physics, Montreal, Quebec (Canada); Sadoff, A.J. [Ithaca College, Ithaca, New York 14850 (United States); Ammar, R.; Baringer, P.; Bean, A.; Besson, D.; Coppage, D.; Darling, C.; Davis, R.; Kotov, S.; Kravchenko, I.; Kwak, N.; Zhou, L. [University of Kansas, Lawrence, Kansas 66045 (United States); Anderson, S.; Kubota, Y.; Lee, S.J.; ONeill, J.J.; Poling, R.; Riehle, T.; Smith, A. [University of Minnesota, Minneapolis, Minnesota 55455 (United States); Alam, M.S.; Athar, S.B.; Ling, Z.; Mahmood, A.H.; Timm, S.; Wappler, F. [State University of New York at Albany, Albany, New York 12222 (United States); Anastassov, A.; Duboscq, J.E.; Fujino, D.; Gan, K.K.; Hart, T.; Honscheid, K.; Kagan, H.; Kass, R.; Lee, J.; Spencer, M.B.; Sung, M.; Undrus, A.; Wolf, A.; Zoeller, M.M. [The Ohio State University, Columbus, Ohio 43210 (United States); Nemati, B.; Richichi, S.J.; Ross, W.R.; Severini, H.; Skubic, P. [University of Oklahoma, Norman, Oklahoma 73019 (United States); Bishai, M.; Fast, J.; Hinson, J.W.; Menon, N.; Miller, D.H.; Shibata, E.I.; Shipsey, I.P.; Yurko, M. [Purdue University, West Lafayette, Indiana 47907 (United States); Glenn, S.; Kwon, Y.; Lyon, A.L.; Roberts, S.; Thorndike, E.H. [University of Rochester, Rochester, New York 14627 (United States); Jessop, C.P.; Lingel, K.; Marsiske, H.; Perl, M.L.; Savinov, V.; Ugolini, D.; Zhou, X.; and others

    1998-08-01

    We report the first observation of B{r_arrow}{eta}{sup {prime}}X transitions with high momentum {eta}{sup {prime}} mesons. We observe 39.0{plus_minus}11.6 B decay events with 2.0{lt}p{sub {eta}{sup {prime}}}{lt}2.7 GeV/c , the high momentum region where background from b{r_arrow}c processes is suppressed. We discuss the physical interpretation of the signal, including the possibility that it is due to b{r_arrow}sg{sup {asterisk}} transitions. Given that interpretation, we find B(B{r_arrow}{eta}{sup {prime}}X{sub s} )=[6.2{plus_minus}1.6(stat){plus_minus} 1.3(syst){sup +0.0}{sub {minus}1.5} (bkg)]{times}10{sup {minus}4} for 2.0{lt}p{sub {eta}{sup {prime}}}{lt}2.7 GeV/c . {copyright} {ital 1998} {ital The American Physical Society }

  11. Leukotriene D4 activates distinct G-proteins in intestinal epithelial cells to regulate stress fibre formation and to generate intracellular Ca2+ mobilisation and ERK1/2 activation

    International Nuclear Information System (INIS)

    Nielsen, Christian Kamp; Massoumi, Ramin; Sonnerlind, Maria; Sjoelander, Anita

    2005-01-01

    We have shown that the pro-inflammatory mediator LTD 4 , via its G-protein-coupled receptor CysLT 1 , signals through both pertussis-toxin-sensitive and -insensitive G-proteins to induce various cellular responses. To further characterise the initial step of the different signalling pathways emanating from the CysLT 1 receptor, we transfected intestinal epithelial cells, Int 407, with different mini vectors that each express a specific inhibitory peptide directed against a unique α subunit of a specific heterotrimeric G-protein. Our results revealed that LTD 4 -induced stress fibre formation is inhibited approximately 80% by a vector expressing an inhibitory peptide against the pertussis-toxin-insensitive Gα 12 -protein in intestinal epithelial Int 407 cells. Control experiments revealed that the LPA-induced stress fibre formation, mediated via the Gα 12 -protein in other cell types, was blocked by the same peptide in intestinal Int 407 cells. Furthermore, the CysLT 1 -receptor-mediated calcium signal and activation of the proliferative ERK1/2 kinase are blocked in cells transfected with a vector expressing an inhibitory peptide against the Gα i3 -protein, whereas in cells transfected with an empty ECFP-vector or vectors expressing inhibitory peptides against the Gα i1-2 -, Gα 12 -, Gα R -proteins these signals are not significantly affected. Consequently, the CysLT 1 receptor has the capacity to activate at least two distinctly different heterotrimeric G-proteins that transduce activation of unique downstream cellular events

  12. Acute respiratory effects and biomarkers of inflammation due to welding-derived nanoparticle aggregates.

    Science.gov (United States)

    Dierschke, Katrin; Isaxon, Christina; Andersson, Ulla B K; Assarsson, Eva; Axmon, Anna; Stockfelt, Leo; Gudmundsson, Anders; Jönsson, Bo A G; Kåredal, Monica; Löndahl, Jakob; Pagels, Joakim; Wierzbicka, Aneta; Bohgard, Mats; Nielsen, Jörn

    2017-07-01

    Welders are exposed to airborne particles from the welding environment and often develop symptoms work-related from the airways. A large fraction of the particles from welding are in the nano-size range. In this study we investigate if the welders' airways are affected by exposure to particles derived from gas metal arc welding in mild steel in levels corresponding to a normal welding day. In an exposure chamber, 11 welders with and 10 welders without work-related symptoms from the lower airways and 11 non-welders without symptoms, were exposed to welding fumes (1 mg/m 3 ) and to filtered air, respectively, in a double-blind manner. Symptoms from eyes and upper and lower airways and lung function were registered. Blood and nasal lavage (NL) were sampled before, immediately after and the morning after exposure for analysis of markers of oxidative stress. Exhaled breath condensate (EBC) for analysis of leukotriene B4 (LT-B4) was sampled before, during and immediately after exposure. No adverse effects of welding exposure were found regarding symptoms and lung function. However, EBC LT-B4 decreased significantly in all participants after welding exposure compared to filtered air. NL IL-6 increased immediately after exposure in the two non-symptomatic groups and blood neutrophils tended to increase in the symptomatic welder group. The morning after, neutrophils and serum IL-8 had decreased in all three groups after welding exposure. Remarkably, the symptomatic welder group had a tenfold higher level of EBC LT-B4 compared to the two groups without symptoms. Despite no clinical adverse effects at welding, changes in inflammatory markers may indicate subclinical effects even at exposure below the present Swedish threshold limit (8 h TWA respirable dust).

  13. Development of 125I-leukotriene B4 radio-immunoassay and its clinical applications

    International Nuclear Information System (INIS)

    Wang Zhaoyue; He Yang; Chen Dechun; Ruan Changgeng

    1992-11-01

    LTB 4 was extracted from porcine blood with the help of HPLC. The antiserum was raised by immunizing rabbits with LTB 4 which has been conjugated with bovine serum albumin by mixed anhydride method method. The titer of the anti-body was 1:7000 and the affinity coefficient was 2.1 x 10 9 L/M. Its cross reactions with LTA 4 , LTC 4 , LTD 4 and other arachidonic acid metabolites were 0.4 ∼ 6.4%.The 125 I-histamine-LTB 4 was prepared by using chloramine T procedure. The minimum detectable limit was 25 pg/tube. The recovery rate was 84.2 ∼ 113%. The intra- and inter-assay coefficient of variation were 5.2% and 9.7% respectively. The amount of LTB 4 produced by normal human PMNL which were stimulated by ionophore A23187 and arachidonic acid was 695.5 ± 329.7 pg/10 6 cells. PMNL of patients with various acute leukemias and CML generated an increased quantities of LTB 4 , TXB 2 and 6-keto-PGF 1α . LTB 4 produced by PMNL also showed an increasing tendency in both cerebral thrombosis and acute myocardial infarction, but was not altered in cerebral hemorrhage of non-infarction coronary disease

  14. Rotavirus 2/6 Viruslike Particles Administered Intranasally with Cholera Toxin, Escherichia coli Heat-Labile Toxin (LT), and LT-R192G Induce Protection from Rotavirus Challenge

    OpenAIRE

    O’Neal, Christine M.; Clements, John D.; Estes, Mary K.; Conner, Margaret E.

    1998-01-01

    We have shown that rotavirus 2/6 viruslike particles composed of proteins VP2 and VP6 (2/6-VLPs) administered to mice intranasally with cholera toxin (CT) induced protection from rotavirus challenge, as measured by virus shedding. Since it is unclear if CT will be approved for human use, we evaluated the adjuvanticity of Escherichia coli heat-labile toxin (LT) and LT-R192G. Mice were inoculated intranasally with 10 μg of 2/6-VLPs combined with CT, LT, or LT-R192G. All three adjuvants induced ...

  15. Comparison of results of simulation of the CONTEMPT-LT/028 and lAP-3B codes for the analysis of the internal vacuum breaker valves of the CNLV

    International Nuclear Information System (INIS)

    Ovando C, R.; Cecenas F, M.; Moya C, M.M.

    2006-01-01

    In the primary container of a BWR type reactor, the humid and dry wells its are communicate by means of valves designed to equal the pressure in case of a significant pressure difference exists, produced by an operative event just as the performance of an emergency system. These valves are known as internal vacuum breakers and its analysis it is made by means of the use of a code with the capacity to analyze the primary contention of the reactor. Among the codes able to carry out this analysis type there is CONTEMPT-LT/028 and MAAP-3B; however, these codes possess characteristic different respect the modeling one of the different damage mitigation systems to the contention (dews, windy, emergency systems), of the transfer of heat among the different compartments of the primary container and in the details of the civil construction. In previous works carried out with the CONTEMPT-LT/028 code, they have been carried out different cases of simulation related with the operation of the internal breaker vacuum valves. These cases include small ruptures in the main steam lines and ruptures in the recirculation knots. It was selected the case more restrictive and it was generated an equivalent scenario file for the MAAP-3B code. In this work the performance of the internal breaker vacuum valves is analyzed by means of the CONTEMPT-LT/028 and MAAP-3B codes, when using the case more restrictive consistent in a small rupture in a main steam line. The analysis of the simulations indicates that both codes produce very similar results and the found differences are explained with base in the models used by each code to obtain the answer of the main thermohydraulic variables. In general terms, MAAP-3B possesses models that adapt in a form more convenient to the prospective phenomenology for this analysis, maintaining a conservative focus. (Author)

  16. Thermoelectric coefficient L(T) of polycrystalline silver doped BSCCO samples

    International Nuclear Information System (INIS)

    Rodriguez, J.E.; Marino, A.

    1998-01-01

    We present a study of the thermoelectric coefficient L(T) of polycrystalline silver doped BSCCO samples. The quantity L(T) relates the thermoelectric coefficient S(T) with the electrical conductivity σ (T) and gives an indication of the influence of the order parameter fluctuations (OPF) on S(T) in the mean field region (Mfr). The results of L(T) indicate that the critical behavior of S(T) above the superconducting transition is not only driven by σ (T). These results suggest that in the Mfr, L(T) is affected by thermodynamic fluctuations of the superconducting order parameter (OPF). The OPF effects show a two-dimensional (2D) character in the entire Mfr. (Author)

  17. Searches for $B^0_{(s)} \\to J/\\psi p\\bar{p}$ and $B^+ \\to J/\\psi p\\bar{p}\\pi^+$ decays

    CERN Document Server

    INSPIRE-00258707; Adeva, B; Adinolfi, M; Adrover, C; Affolder, A; Ajaltouni, Z; Albrecht, J; Alessio, F; Alexander, M; Ali, S; Alkhazov, G; Alvarez Cartelle, P; Alves Jr, A A; Amato, S; Amerio, S; Amhis, Y; Anderlini, L; Anderson, J; Andreassen, R; Andrews, J E; Appleby, R B; Aquines Gutierrez, O; Archilli, F; Artamonov, A; Artuso, M; Aslanides, E; Auriemma, G; Baalouch, M; Bachmann, S; Back, J J; Baesso, C; Balagura, V; Baldini, W; Barlow, R J; Barschel, C; Barsuk, S; Barter, W; Bauer, Th; Bay, A; Beddow, J; Bedeschi, F; Bediaga, I; Belogurov, S; Belous, K; Belyaev, I; Ben-Haim, E; Bencivenni, G; Benson, S; Benton, J; Berezhnoy, A; Bernet, R; Bettler, M -O; van Beuzekom, M; Bien, A; Bifani, S; Bird, T; Bizzeti, A; Bjørnstad, P M; Blake, T; Blanc, F; Blouw, J; Blusk, S; Bocci, V; Bondar, A; Bondar, N; Bonivento, W; Borghi, S; Borgia, A; Bowcock, T J V; Bowen, E; Bozzi, C; Brambach, T; van den Brand, J; Bressieux, J; Brett, D; Britsch, M; Britton, T; Brook, N H; Brown, H; Burducea, I; Bursche, A; Busetto, G; Buytaert, J; Cadeddu, S; Callot, O; Calvi, M; Calvo Gomez, M; Camboni, A; Campana, P; Campora Perez, D; Carbone, A; Carboni, G; Cardinale, R; Cardini, A; Carranza-Mejia, H; Carson, L; Carvalho Akiba, K; Casse, G; Castillo Garcia, L; Cattaneo, M; Cauet, Ch; Cenci, R; Charles, M; Charpentier, Ph; Chen, P; Chiapolini, N; Chrzaszcz, M; Ciba, K; Cid Vidal, X; Ciezarek, G; Clarke, P E L; Clemencic, M; Cliff, H V; Closier, J; Coca, C; Coco, V; Cogan, J; Cogneras, E; Collins, P; Comerma-Montells, A; Contu, A; Cook, A; Coombes, M; Coquereau, S; Corti, G; Couturier, B; Cowan, G A; Craik, D C; Cunliffe, S; Currie, R; D'Ambrosio, C; David, P; David, P N Y; Davis, A; De Bonis, I; De Bruyn, K; De Capua, S; De Cian, M; De Miranda, J M; De Paula, L; De Silva, W; De Simone, P; Decamp, D; Deckenhoff, M; Del Buono, L; Déléage, N; Derkach, D; Deschamps, O; Dettori, F; Di Canto, A; Di Ruscio, F; Dijkstra, H; Dogaru, M; Donleavy, S; Dordei, F; Dosil Suárez, A; Dossett, D; Dovbnya, A; Dupertuis, F; Durante, P; Dzhelyadin, R; Dziurda, A; Dzyuba, A; Easo, S; Egede, U; Egorychev, V; Eidelman, S; van Eijk, D; Eisenhardt, S; Eitschberger, U; Ekelhof, R; Eklund, L; El Rifai, I; Elsasser, Ch; Falabella, A; Färber, C; Fardell, G; Farinelli, C; Farry, S; Fave, V; Ferguson, D; Fernandez Albor, V; Ferreira Rodrigues, F; Ferro-Luzzi, M; Filippov, S; Fiore, M; Fitzpatrick, C; Fontana, M; Fontanelli, F; Forty, R; Francisco, O; Frank, M; Frei, C; Frosini, M; Furcas, S; Furfaro, E; Gallas Torreira, A; Galli, D; Gandelman, M; Gandini, P; Gao, Y; Garofoli, J; Garosi, P; Garra Tico, J; Garrido, L; Gaspar, C; Gauld, R; Gersabeck, E; Gersabeck, M; Gershon, T; Ghez, Ph; Gibson, V; Giubega, L; Gligorov, V V; Göbel, C; Golubkov, D; Golutvin, A; Gomes, A; Gordon, H; Grabalosa Gándara, M; Graciani Diaz, R; Granado Cardoso, L A; Graugés, E; Graziani, G; Grecu, A; Greening, E; Gregson, S; Griffith, P; Grünberg, O; Gui, B; Gushchin, E; Guz, Yu; Gys, T; Hadjivasiliou, C; Haefeli, G; Haen, C; Haines, S C; Hall, S; Hamilton, B; Hampson, T; Hansmann-Menzemer, S; Harnew, N; Harnew, S T; Harrison, J; Hartmann, T; He, J; Head, T; Heijne, V; Hennessy, K; Henrard, P; Hernando Morata, J A; van Herwijnen, E; Hicheur, A; Hicks, E; Hill, D; Hoballah, M; Holtrop, M; Hombach, C; Hopchev, P; Hulsbergen, W; Hunt, P; Huse, T; Hussain, N; Hutchcroft, D; Hynds, D; Iakovenko, V; Idzik, M; Ilten, P; Jacobsson, R; Jaeger, A; Jans, E; Jaton, P; Jawahery, A; Jing, F; John, M; Johnson, D; Jones, C R; Joram, C; Jost, B; Kaballo, M; Kandybei, S; Kanso, W; Karacson, M; Karbach, T M; Kenyon, I R; Ketel, T; Keune, A; Khanji, B; Kochebina, O; Komarov, I; Koopman, R F; Koppenburg, P; Korolev, M; Kozlinskiy, A; Kravchuk, L; Kreplin, K; Kreps, M; Krocker, G; Krokovny, P; Kruse, F; Kucharczyk, M; Kudryavtsev, V; Kvaratskheliya, T; La Thi, V N; Lacarrere, D; Lafferty, G; Lai, A; Lambert, D; Lambert, R W; Lanciotti, E; Lanfranchi, G; Langenbruch, C; Latham, T; Lazzeroni, C; Le Gac, R; van Leerdam, J; Lees, J -P; Lefèvre, R; Leflat, A; Lefrançois, J; Leo, S; Leroy, O; Lesiak, T; Leverington, B; Li, Y; Li Gioi, L; Liles, M; Lindner, R; Linn, C; Liu, B; Liu, G; Lohn, S; Longstaff, I; Lopes, J H; Lopez-March, N; Lu, H; Lucchesi, D; Luisier, J; Luo, H; Machefert, F; Machikhiliyan, I V; Maciuc, F; Maev, O; Malde, S; Manca, G; Mancinelli, G; Maratas, J; Marconi, U; Marino, P; Märki, R; Marks, J; Martellotti, G; Martens, A; Martín Sánchez, A; Martinelli, M; Martinez Santos, D; Martins Tostes, D; Massafferri, A; Matev, R; Mathe, Z; Matteuzzi, C; Maurice, E; Mazurov, A; Mc Skelly, B; McCarthy, J; McNab, A; McNulty, R; Meadows, B; Meier, F; Meissner, M; Merk, M; Milanes, D A; Minard, M -N; Molina Rodriguez, J; Monteil, S; Moran, D; Morawski, P; Mordà, A; Morello, M J; Mountain, R; Mous, I; Muheim, F; Müller, K; Muresan, R; Muryn, B; Muster, B; Naik, P; Nakada, T; Nandakumar, R; Nasteva, I; Needham, M; Neubert, S; Neufeld, N; Nguyen, A D; Nguyen, T D; Nguyen-Mau, C; Nicol, M; Niess, V; Niet, R; Nikitin, N; Nikodem, T; Nomerotski, A; Novoselov, A; Oblakowska-Mucha, A; Obraztsov, V; Oggero, S; Ogilvy, S; Okhrimenko, O; Oldeman, R; Orlandea, M; Otalora Goicochea, J M; Owen, P; Oyanguren, A; Pal, B K; Palano, A; Palutan, M; Panman, J; Papanestis, A; Pappagallo, M; Parkes, C; Parkinson, C J; Passaleva, G; Patel, G D; Patel, M; Patrick, G N; Patrignani, C; Pavel-Nicorescu, C; Pazos Alvarez, A; Pellegrino, A; Penso, G; Pepe Altarelli, M; Perazzini, S; Perez Trigo, E; Pérez-Calero Yzquierdo, A; Perret, P; Perrin-Terrin, M; Pescatore, L; Pessina, G; Petridis, K; Petrolini, A; Phan, A; Picatoste Olloqui, E; Pietrzyk, B; Pilař, T; Pinci, D; Playfer, S; Plo Casasus, M; Polci, F; Polok, G; Poluektov, A; Polycarpo, E; Popov, A; Popov, D; Popovici, B; Potterat, C; Powell, A; Prisciandaro, J; Pritchard, A; Prouve, C; Pugatch, V; Puig Navarro, A; Punzi, G; Qian, W; Rademacker, J H; Rakotomiaramanana, B; Rangel, M S; Raniuk, I; Rauschmayr, N; Raven, G; Redford, S; Reid, M M; dos Reis, A C; Ricciardi, S; Richards, A; Rinnert, K; Rives Molina, V; Roa Romero, D A; Robbe, P; Roberts, D A; Rodrigues, E; Rodriguez Perez, P; Roiser, S; Romanovsky, V; Romero Vidal, A; Rouvinet, J; Ruf, T; Ruffini, F; Ruiz, H; Ruiz Valls, P; Sabatino, G; Saborido Silva, J J; Sagidova, N; Sail, P; Saitta, B; Salustino Guimaraes, V; Salzmann, C; Sanmartin Sedes, B; Sannino, M; Santacesaria, R; Santamarina Rios, C; Santovetti, E; Sapunov, M; Sarti, A; Satriano, C; Satta, A; Savrie, M; Savrina, D; Schaack, P; Schiller, M; Schindler, H; Schlupp, M; Schmelling, M; Schmidt, B; Schneider, O; Schopper, A; Schune, M -H; Schwemmer, R; Sciascia, B; Sciubba, A; Seco, M; Semennikov, A; Sepp, I; Serra, N; Serrano, J; Seyfert, P; Shapkin, M; Shapoval, I; Shatalov, P; Shcheglov, Y; Shears, T; Shekhtman, L; Shevchenko, O; Shevchenko, V; Shires, A; Silva Coutinho, R; Sirendi, M; Skwarnicki, T; Smith, N A; Smith, E; Smith, J; Smith, M; Sokoloff, M D; Soler, F J P; Soomro, F; Souza, D; Souza De Paula, B; Spaan, B; Sparkes, A; Spradlin, P; Stagni, F; Stahl, S; Steinkamp, O; Stoica, S; Stone, S; Storaci, B; Straticiuc, M; Straumann, U; Subbiah, V K; Sun, L; Swientek, S; Syropoulos, V; Szczekowski, M; Szczypka, P; Szumlak, T; T'Jampens, S; Teklishyn, M; Teodorescu, E; Teubert, F; Thomas, C; Thomas, E; van Tilburg, J; Tisserand, V; Tobin, M; Tolk, S; Tonelli, D; Topp-Joergensen, S; Torr, N; Tournefier, E; Tourneur, S; Tran, M T; Tresch, M; Tsaregorodtsev, A; Tsopelas, P; Tuning, N; Ubeda Garcia, M; Ukleja, A; Urner, D; Ustyuzhanin, A; Uwer, U; Vagnoni, V; Valenti, G; Vallier, A; Van Dijk, M; Vazquez Gomez, R; Vazquez Regueiro, P; Vázquez Sierra, C; Vecchi, S; Velthuis, J J; Veltri, M; Veneziano, G; Vesterinen, M; Viaud, B; Vieira, D; Vilasis-Cardona, X; Vollhardt, A; Volyanskyy, D; Voong, D; Vorobyev, A; Vorobyev, V; Voß, C; Voss, H; Waldi, R; Wallace, C; Wallace, R; Wandernoth, S; Wang, J; Ward, D R; Watson, N K; Webber, A D; Websdale, D; Whitehead, M; Wicht, J; Wiechczynski, J; Wiedner, D; Wiggers, L; Wilkinson, G; Williams, M P; Williams, M; Wilson, F F; Wimberley, J; Wishahi, J; Witek, M; Wotton, S A; Wright, S; Wu, S; Wyllie, K; Xie, Y; Xing, Z; Yang, Z; Young, R; Yuan, X; Yushchenko, O; Zangoli, M; Zavertyaev, M; Zhang, F; Zhang, L; Zhang, W C; Zhang, Y; Zhelezov, A; Zhokhov, A; Zhong, L; Zvyagin, A

    2013-01-01

    The results of searches for $B^0_{(s)} \\to J/\\psi p\\bar{p}$ and $B^+ \\to J/\\psi p\\bar{p}\\pi^+$ decays are reported. The analysis is based on a data sample, corresponding to an integrated luminosity of 1.0 fb$^{-1}$ of $pp$ collisions, collected with the LHCb detector. An excess with 2.8 $\\sigma$ significance is seen for the decay $B^0_{s} \\to J/\\psi p\\bar{p}$ and an upper limit on the branching fraction is set at the 90% confidence level: $B(B^0_s \\to J/\\psi p\\bar{p}) \\lt$ 4.8 x 10$^{-6}$, which is the first such limit. No significant signals are seen for $B^0 \\to J/\\psi p\\bar{p}$ and $B^+ \\to J/\\psi p\\bar{p}\\pi^+$ decays, for which the corresponding limits are set: $B(B^0 \\to J/\\psi p\\bar{p}) \\lt$ 5.2 x 10$^{-7}$, which significantly improves the existing limit; and $B(B^+ \\to J/\\psi p\\bar{p}\\pi^+) \\lt$ 5.0 x 10$^{-7}$, which is the first limit on this branching fraction.

  18. Solubilization and cleavage of human neutrophil (N) affinity-labeled receptors for leukotriene B4 (LTB4)

    International Nuclear Information System (INIS)

    Marotti, T.; Young, R.N.; Gifford, L.A.; Goldman, D.W.; Goetzl, E.J.

    1986-01-01

    LTB 4 chemotactic receptors in purified N plasma membranes (PMs) have been affinity-labeled with [ 3 H]-C-1 aminopropylamide-LTB 4 ([ 3 H]APA-LTB 4 ) by disuccinimidyl suberate (DSS) cross-linking. Intact Ns were pretreated with diisopropylfluorophosphate, suspended at 10 7 /ml in Hanks' solution-10 mM HEPES (pH 7.4), incubated for 30 min at 4 0 C with 30 nM [ 3 H]APA-LTB 4 and 25 min with 1 mM bis[2-(succinimidooxycarbonyloxy)-ethyl] sulfone, an impermeant analog of DSS, and sonified for 30 sec at 4 0 C. The 10,000 g supernatant of the sonicate was centrifuged at 40,000 g for 30 min at 4 0 C on a discontinuous gradient of 10-50 g % sucrose, from which a mean of 78% of the radiolabel was recovered with PM markers. The extent and specificity of labeling of intact N receptors were similar to those of receptors in PMs. The radioactively-labeled receptors appeared as a single band of 35-40 kd in sodium dodecyl sulfate (SDS) 10 g % polyacrylamide gel electrophoresis. Cleavage of radiolabeled receptors with 1 mg/ml of cyanogen bromide in 70% formic acid for 18 hr at room temperature or with 30 mM HCl under N 2 for 4 hr at 105 0 C converted a mean of 18-32% of the radioactivity to a band of 14 kd in SDS-15 g % PAGE. N receptors for LTB 4 , thus, are localized in the PM and can be isolated for structural studies

  19. LIN28B polymorphisms are associated with central precocious puberty and early puberty in girls

    Directory of Open Access Journals (Sweden)

    Sung Won Park

    2012-10-01

    Full Text Available &lt;B&gt;Purpose:&lt;/B&gt; Single-nucleotide polymorphism (SNP markers within &lt;i&gt;LIN28B&lt;/i&gt; have been reported to be related to the timing of pubertal growth. However, no study has investigated the frequency of genetic markers in girls with precocious puberty (PP or early puberty (EP. This study aimed to determine the frequency of putative genetic markers in girls with PP or EP. &lt;B&gt;Methods:&lt;/B&gt; Genomic DNAs were obtained from 77 and 109 girls that fulfilled the criteria for PP and EP, respectively. The controls in this study were 144 healthy volunteers between 20 and 30 years of age. The haplotypes were reconstructed using 11 SNPs of &lt;i&gt;LIN28B&lt;/i&gt;, and haplotype association analysis was performed. The haplotype frequencies were compared. Differences in the clinical and laboratory parameters were analyzed according to the haplotype dosage. &lt;B&gt;Results:&lt;/B&gt; Eleven SNPs in &lt;i&gt;LIN28B&lt;/i&gt; were all located in a block that was in linkage disequilibrium. The haplotype could be reconstructed using 2 representative SNPs, rs4946651 and rs369065. The AC haplotype was less frequently observed in the PP group than in the controls (0.069 vs. 0.144, &lt;I&gt;P&lt;/I&gt;=0.010. The trend that girls with non-AC haplotypes tended to have earlier puberty onset (&lt;I&gt;P&lt;/I&gt;=0.037 was illustrated even in the EP+PP patient group by Kaplan-Meier analysis. &lt;B&gt;Conclusion:&lt;/B&gt; The results of the present study showed that non-AC haplotypes of &lt;i&gt;LIN28B&lt;/i&gt;had a significant association with PP in girls.

  20. Trigon Farming ostis Kaiu LT / Margus Mikomägi

    Index Scriptorium Estoniae

    Mikomägi, Margus, 1956-

    2006-01-01

    Raplamaalt suuruselt neljas põllumajandusühistu Kaiu LT müüdi üldkoosoleku otsusega ühel häälel firmale Trigon Farming. Kaiu LT nõukogu esimees on viimased kolm aastat olnud Riigikogu liige Tiit Tammsaar. Lisa: Trigon Tarming investeerib põllumajandusse

  1. Type II heat-labile enterotoxins from 50 diverse Escherichia coli isolates belong almost exclusively to the LT-IIc family and may be prophage encoded.

    Directory of Open Access Journals (Sweden)

    Michael G Jobling

    Full Text Available Some enterotoxigenic Escherichia coli (ETEC produce a type II heat-labile enterotoxin (LT-II that activates adenylate cyclase in susceptible cells but is not neutralized by antisera against cholera toxin or type I heat-labile enterotoxin (LT-I. LT-I variants encoded by plasmids in ETEC from humans and pigs have amino acid sequences that are ≥ 95% identical. In contrast, LT-II toxins are chromosomally encoded and are much more diverse. Early studies characterized LT-IIa and LT-IIb variants, but a novel LT-IIc was reported recently. Here we characterized the LT-II encoding loci from 48 additional ETEC isolates. Two encoded LT-IIa, none encoded LT-IIb, and 46 encoded highly related variants of LT-IIc. Phylogenetic analysis indicated that the predicted LT-IIc toxins encoded by these loci could be assigned to 6 subgroups. The loci corresponding to individual toxins within each subgroup had DNA sequences that were more than 99% identical. The LT-IIc subgroups appear to have arisen by multiple recombinational events between progenitor loci encoding LT-IIc1- and LT-IIc3-like variants. All loci from representative isolates encoding the LT-IIa, LT-IIb, and each subgroup of LT-IIc enterotoxins are preceded by highly-related genes that are between 80 and 93% identical to predicted phage lysozyme genes. DNA sequences immediately following the B genes differ considerably between toxin subgroups, but all are most closely related to genomic sequences found in predicted prophages. Together these data suggest that the LT-II loci are inserted into lambdoid type prophages that may or may not be infectious. These findings raise the possibility that production of LT-II enterotoxins by ETEC may be determined by phage conversion and may be activated by induction of prophage, in a manner similar to control of production of Shiga-like toxins by converting phages in isolates of enterohemmorhagic E. coli.

  2. Resuscitation of the viable but non-culturable state of Salmonella enterica serovar Oranienburg by recombinant resuscitation-promoting factor derived from Salmonella Typhimurium strain LT2.

    Science.gov (United States)

    Panutdaporn, N; Kawamoto, K; Asakura, H; Makino, S-I

    2006-02-15

    A gene encoding the resuscitation-promoting factor (Rpf) from Salmonella Typhimurium LT2 was cloned and characterized. The amino acid sequence encoded by S. Typhimurium LT2 rpf gene shares 24.2% homology with Micrococcus luteus Rpf, which is secreted by growing cells, and required to resuscitate from viable but non-culturable (VNC) state. The S. Typhimurium LT2 rpf gene is 696 bp long, and shared a conserved segment with Salmonella enterica serovar Oranienburg (99.4%). Recombinant Rpf (rRpf) proteins of S. Typhimurium LT2 after expression in E. coli BL21 harboring the pET15-b plasmid was approximately 25 kDa. Since S. Oranienburg cells are relatively quick to enter the VNC state just after incubating in the presence of 7% NaCl at 37 degrees C for 3 days, we evaluated the biological effect of rRpf by using S. Oranienburg VNC cells. The rRpf not only promoted proliferation but also induced resuscitation of VNC cells to the culturable state in a dose-dependent manner. Therefore, rRpf may be useful for detection of bacterial contaminants present in the VNC form in food samples and the environment.

  3. 8-Isoprostane and leukotrienes in exhaled breath condensate in czech subjects with silicosis

    Czech Academy of Sciences Publication Activity Database

    Pelclová, D.; Fenclová, Z.; Kačer, P.; Navrátil, Tomáš; Kuzma, Marek; Lebedová, J.; Klusáčková, P.

    2007-01-01

    Roč. 45, č. 6 (2007), s. 766-774 ISSN 0019-8366 Grant - others:GA MZd NR8107 Institutional research plan: CEZ:AV0Z40400503; CEZ:AV0Z50200510 Keywords : silica * silicosis * 8-isoprostane * leukotrienes Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 0.792, year: 2007

  4. Prostaglandin (PG) E3 synthesis elicted by adrenergic stimuli in guinea-pig trachea (GPT) is mediated primarily by B2 adrenergic receptors

    International Nuclear Information System (INIS)

    Nadel, G.L.; Malik, K.U.; Lew, D.B.

    1990-01-01

    The purpose of this study was to examine arachidonic acid (AA) metabolism and to characterize the type of adrenergic receptor (AR) involved in the production of the major metabolite of this fatty acid. [ 14 C]AA was incubated with GPT-rings and the radiolabelled products were extracted and separated by TLC method. The medium was also assayed for radiolabelled immunoreactive PG's (iPG's) and leukotrienes (LT) B4 and C4 by RIA or Enzyme immunoassay (EIA) after exposure to various AR agonists. [ 14 C]AA was incorporated into GPT-rings and metabolized mainly into iPGE2 and smaller amounts into PGF2α. Trace amounts of PGD2 and 6-keto-PGF1α but not LTB4 or LTC4 were detected by RIA and/or EIA. Incubation of GPT rings for 15 minutes with isoproterenol and salbutamol resulted in a significant increase of PGE2 synthesis (optimum conc: 10 -7 , 10 -7 M respectively). In contrast, dobutamine, norepinephrine, phenylnephrine and xylazine (up to 10 -6 M) did not significantly increase PGE2 production. Isoproterenol-induced iPGE2 production was inhibited by a selective β2 antagonist, butoxamine (70%: 10 -7 M, 91%: 10 -6 M) and somewhat reduced by β1 antagonists practolol and metoprolol (30-64%:10 -6 M). These data suggest that isoproterenol induced iPGE2 synthesis is primarily mediated via activation of β2 adrenergic receptor

  5. Exhaled Leukotrienes and Bronchial Responsiveness to Methacholine in Patients with Seasonal Allergic Rhinitis

    Czech Academy of Sciences Publication Activity Database

    Čáp, P.; Malý, Marek; Pehal, F.; Pelikán, Z.

    2009-01-01

    Roč. 102, č. 2 (2009), s. 103-109 ISSN 1081-1206 Grant - others:GA MZd(CZ) NL7024 Institutional research plan: CEZ:AV0Z10300504 Keywords : allergic rhinitis * asthma * breath condensate * leukotrienes * gas chromatography * mass spectrometry analysis Subject RIV: FN - Epidemiology, Contagious Diseases ; Clinical Immunology Impact factor: 2.457, year: 2009

  6. Discovery of a visual T-dwarf triple system and binarity at the L/T transition

    Energy Technology Data Exchange (ETDEWEB)

    Radigan, Jacqueline [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States); Jayawardhana, Ray [Department of Astronomy and Astrophysics, University of Toronto, 50 St. George Street, Toronto, ON M5S 3H4 (Canada); Lafrenière, David [Département de Physique, Université de Montréal, C.P. 6128 Succ. Centre-Ville, Montréal, QC H3C 3J7 (Canada); Dupuy, Trent J. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Liu, Michael C. [Institute for Astronomy, University of Hawaii, 2680 Woodlawn Drive, Honolulu, HI 96822 (United States); Scholz, Alexander, E-mail: radigan@stsci.edu [School of Physics and Astronomy, University of St Andrews, North Haugh, St Andrews, KY169SS (United Kingdom)

    2013-11-20

    We present new high contrast imaging of eight L/T transition brown dwarfs (BDs) using the NIRC2 camera on the Keck II telescope. One of our targets, the T3.5 dwarf 2MASS J08381155+1511155, was resolved into a hierarchal triple with projected separations of 2.5 ± 0.5 AU and 27 ± 5 AU for the BC and A(BC) components, respectively. Resolved OSIRIS spectroscopy of the A(BC) components confirms that all system members are T dwarfs. The system therefore constitutes the first triple T-dwarf system ever reported. Using resolved photometry to model the integrated-light spectrum, we infer spectral types of T3 ± 1, T3 ± 1, and T4.5 ± 1 for the A, B, and C components, respectively. The uniformly brighter primary has a bluer J – K{sub s} color than the next faintest component, which may reflect a sensitive dependence of the L/T transition temperature on gravity, or alternatively divergent cloud properties among components. Relying on empirical trends and evolutionary models we infer a total system mass of 0.034-0.104 M {sub ☉} for the BC components at ages of 0.3-3 Gyr, which would imply a period of 12-21 yr assuming the system semimajor axis to be similar to its projection. We also infer differences in effective temperatures and surface gravities between components of no more than ∼150 K and ∼0.1 dex. Given the similar physical properties of the components, the 2M0838+15 system provides a controlled sample for constraining the relative roles of effective temperature, surface gravity, and dust clouds in the poorly understood L/T transition regime. For an age of 3 Gyr we estimate a binding energy of ∼20 × 10{sup 41} erg for the wide A(BC) pair, which falls above the empirical minimum found for typical BD binaries, and suggests that the system may have been able to survive a dynamical ejection during formation. Combining our imaging survey results with previous work we find an observed binary fraction of 4/18 or 22{sub −8}{sup +10}% for unresolved spectral types

  7. Design and Analysis of LT Codes with Decreasing Ripple Size

    DEFF Research Database (Denmark)

    Sørensen, Jesper Hemming; Popovski, Petar; Østergaard, Jan

    2012-01-01

    In this paper we propose a new design of LT codes, which decreases the amount of necessary overhead in comparison to existing designs. The design focuses on a parameter of the LT decoding process called the ripple size. This parameter was also a key element in the design proposed in the original...... work by Luby. Specifically, Luby argued that an LT code should provide a constant ripple size during decoding. In this work we show that the ripple size should decrease during decoding, in order to reduce the necessary overhead. Initially we motivate this claim by analytical results related...... to the redundancy within an LT code. We then propose a new design procedure, which can provide any desired achievable decreasing ripple size. The new design procedure is evaluated and compared to the current state of the art through simulations. This reveals a significant increase in performance with respect...

  8. The IL1B-511 Polymorphism (rs16944 AA Genotype) Is Increased in Aspirin-Exacerbated Respiratory Disease in Mexican Population.

    Science.gov (United States)

    Falfán-Valencia, Ramcés; Pavón-Romero, Gandhi F; Camarena, Angel; García, María de la Luz; Galicia-Negrete, Gustavo; Negrete-García, María Cristina; Teran, Luis Manuel

    2012-01-01

    Aspirin exacerbated respiratory disease (AERD) is characterized by chronic hyperplastic rhinosinusitis, nasal polyposis, asthma, and aspirin sensitivity. The mechanisms which produce these manifestations of intolerance are not fully defined, current research focuses on cyclooxygenase 1 (COX-1) inhibition, metabolism of arachidonic acid, and the COX pathway to the lipoxygenase (LO) route, inducing increased synthesis of leukotrienes (LT). The biological plausibility of this model has led to the search for polymorphisms in genes responsible for proinflammatory cytokines synthesis, such as IL1B and IL8. We performed a genetic association study between IL8-251 (rs4073) and IL1B-511 (rs16944) polymorphisms in AERD, aspirin-tolerant asthma (ATA), and healthy control subjects. Using allelic discrimination by real-time PCR, we found statistically nonsignificant associations between AERD, ATA, and healthy control subjects for the GG and GA genotypes of IL1B (rs16944). Interestingly, the AA genotype showed an increased frequency in the AERD patients versus the ATA group (GF = 0.19 versus 0.07, p = 0.018, OR 2.98, and 95% CI 1.17-7.82). This is the first observation that IL1B polymorphisms are involved in AERD. Thus, future studies must investigate whether interleukin-1β is released in the airways of AERD patients and whether it relates to genetic polymorphisms in the IL1B gene.

  9. Mainosideoista sähköisiin sisältöihin : sisältöstrategian merkitys mainostoimistojen digitaalisissa palveluissa

    OpenAIRE

    Pasanen, Riikka

    2012-01-01

    Sisältöstrategia on suunnittelukäytäntö, jonka tähtää liiketoiminnallisiin tavoitteisiin vaikuttavan verkkosisällön avulla. Tutkimuksessa tarkastellaan hyvän verkkosisällön kriteerejä ja pohditaan, voisiko mainostoimisto ottaa oppia sisältöstrategian käytännöistä ja tarjota sen avulla parempaa palvelua asiakkailleen. Tutkimusta varten on haastateltu neljää mainonnan strategisen suunnittelun ja asiakasjohdon ammattilaista, joiden näkemyksiä on peilattu tutkijan pitkään kokemukseen alalta sekä ...

  10. Leukotriene B4 (LTB4) induces formation of inositol-phosphates (IP's) in rat peritoneal polymorphonuclear leukocytes (PMN's)

    International Nuclear Information System (INIS)

    Chi-Rosso, G.; Crooke, S.T.; Mong, S.

    1986-01-01

    LTB 4 induced rapid breakdown of prelabeled inositol-phospholipids (PI) in rat PMN. Formation of [ 3 H]-inositol-trisphosphate ([ 3 H]-IP 3 ) was rapid, with a peak of 250-300% of the control level, after 5-15 sec of stimulation with LTB 4 . Accumulation of [ 3 H]-inositol-bisphosphate ([ 3 H]-IP 2 ) was rapid, peaking after 30 sec of stimulation. [ 3 H]-inositol-monophosphate ([ 3 H]-IP 1 ) accumulated gradually in the presence of LiCl. The kinetics of [ 3 H]-IP 3 , [ 3 H]-IP 2 and [ 3 H]-IP 1 accumulation suggested that LTB 4 may interact with receptors in PMNs, activate phospholipase C which, in turn, induces hydrolysis of PI. The agonist activities of several LTB 4 analogs were employed to investigate the structure activity relationship of LTB 4 receptor mediated activation of PI hydrolysis. Increases in [ 3 H]-IP 3 formation were dependent upon the concentration of LTB 4 and the agonist analogs. The rank order potency of these analogs were equivalent to that of the pharmacological activity of LTB 4 agonists in the chemotaxis assay. Furthermore, the Islet activation protein (IAP) inhibited LTB 4 induced [ 3 H]-IP 3 formation. The tumor promoting phorbomyristate ester also inhibited LTB 4 induced [ 3 H]-IP 3 formation. These results suggest LTB 4 may interact with receptors in rat PMNs, activate G/sub i/ protein regulated phospholipase C and induce [ 3 H]-IP 3 formation

  11. Churg-Strauss syndrome and leukotriene antagonist use: a respiratory perspective.

    LENUS (Irish Health Repository)

    Nathani, N

    2008-10-01

    Churg-Strauss syndrome (CSS) is a rare granulomatous small vessel vasculitis that occurs against a background of longstanding asthma. Leukotriene antagonists (LTAs) are used in the management of asthma and may facilitate a reduction in steroid dosage. Reports of the development of CSS in patients with asthma following the initiation of LTA therapy suggest either a causal association or an unmasking of latent CSS as steroid doses fall. We have undertaken a systematic review to establish whether evidence of a drug induced syndrome exists.

  12. Determination of cysteinyl leukotrienes in exhaled breath condensate: Method combining immunoseparation with LC-ESI-MS/MS

    Czech Academy of Sciences Publication Activity Database

    Syslová, K.; Kačer, P.; Vilhanová, B.; Kuzma, Marek; Lipovová, P.; Fenclová, Z.; Lebedová, J.; Pelclová, D.

    2011-01-01

    Roč. 879, č. 23 (2011), s. 2220-2228 ISSN 1570-0232 R&D Projects: GA MZd NS10298 Keywords : Cysteinyl leukotriene * Exhaled breath condensate * Immunoseparation Subject RIV: CE - Biochemistry Impact factor: 2.888, year: 2011

  13. Intranasal Administration of 2/6-Rotavirus-Like Particles with Mutant Escherichia coli Heat-Labile Toxin (LT-R192G) Induces Antibody-Secreting Cell Responses but Not Protective Immunity in Gnotobiotic Pigs

    Science.gov (United States)

    Yuan, Lijuan; Geyer, Annelise; Hodgins, Douglas C.; Fan, Zhiqian; Qian, Yuan; Chang, Kyeong-Ok; Crawford, Sue E.; Parreño, Viviana; Ward, Lucy A.; Estes, Mary K.; Conner, Margaret E.; Saif, Linda J.

    2000-01-01

    We investigated the immunogenicity of recombinant double-layered rotavirus-like particle (2/6-VLPs) vaccines derived from simian SA11 or human (VP6) Wa and bovine RF (VP2) rotavirus strains. The 2/6-VLPs were administered to gnotobiotic pigs intranasally (i.n.) with a mutant Escherichia coli heat-labile toxin, LT-R192G (mLT), as mucosal adjuvant. Pigs were challenged with virulent Wa (P1A[8],G1) human rotavirus at postinoculation day (PID) 21 (two-dose VLP regimen) or 28 (three-dose VLP regimen). In vivo antigen-activated antibody-secreting cells (ASC) (effector B cells) and in vitro antigen-reactivated ASC (derived from memory B cells) from intestinal and systemic lymphoid tissues (duodenum, ileum, mesenteric lymph nodes [MLN], spleen, peripheral blood lymphocytes [PBL], and bone marrow lymphocytes) collected at selected times were quantitated by enzyme-linked immunospot assays. Rotavirus-specific immunoglobulin M (IgM), IgA, and IgG ASC and memory B-cell responses were detected by PID 21 or 28 in intestinal and systemic lymphoid tissues after i.n. inoculation with two or three doses of 2/6-VLPs with or without mLT. Greater mean numbers of virus-specific ASC and memory B cells in all tissues prechallenge were induced in pigs inoculated with two doses of SA11 2/6-VLPs plus mLT compared to SA11 2/6-VLPs without mLT. After challenge, anamnestic IgA and IgG ASC and memory B-cell responses were detected in intestinal lymphoid tissues of all VLP-inoculated groups, but serum virus-neutralizing antibody titers were not significantly enhanced compared to the challenged controls. Pigs inoculated with Wa-RF 2/6-VLPs (with or without mLT) developed higher anamnestic IgA and IgG ASC responses in ileum after challenge compared to pigs inoculated with SA11 2/6-VLPs (with or without mLT). Three doses of SA 11 2/6-VLP plus mLT induced the highest mean numbers of IgG memory B cells in MLN, spleen, and PBL among all groups postchallenge. However, no significant protection against

  14. The Application of LT-Table in TRIZ Contradiction Resolving Process

    Science.gov (United States)

    Wei, Zihui; Li, Qinghai; Wang, Donglin; Tian, Yumei

    TRIZ is used to resolve invention problems. ARIZ is the most powerful systematic method which integrates all of TRIZ heuristics. Definition of ideal final result (IFR), identification of contradictions and resource utilization are main lines of ARIZ. But resource searching of ARIZ has fault of blindness. Alexandr sets up mathematical model of transformation of the hereditary information in an invention problem using the theory of catastrophes, and provides method of resource searching using LT-table. The application of LT-table on contradiction resolving is introduced. Resource utilization using LT-table is joined into ARIZ step as an addition of TRIZ, apply this method in separator paper punching machine design.

  15. Effects of drugs inhibiting prostaglandin or leukotriene biosynthesis on postirradiation haematopoiesis in mouse

    International Nuclear Information System (INIS)

    Kozubik, A.; Hofmanova, J.; Pospisil, M.; Netikova, J.; Hola, J.; Lojek, A.

    1994-01-01

    Two non-steroidal anti-inflammatory drugs, i.e. indomethacin (INDO), an inhibitor of prostaglandin production, and esculetin (ESCUL), an inhibitor of leukotriene production, were tested for their ability to modify haematopoiesis in three experimental systems: (a) in vitro clonal proliferation of marrow GM-CFC from the irradiated mouse was found to be augmented by addition of INDO at a low concentration, and inhibited by ESCUL in a dose-dependent manner; (b) in the lethally irradiated and bone marrow-transplanted mice treated with the drugs in the postirradiation period, stimulatory effects of INDO on CFU-S and GM-CFC populations and an inhibitory effect of ESCUL on GM-CFC were observed; and (c) when the drugs were administered i.p. to mice 1 h before 5-Gy irradiation, INDO enhanced the postirradiation recovery of haematopoietic indices such the numbers of CFU-S, GM-CFC, peripheral blood granuloctyes, and nucleated bone marrow cells, while ESCUL had no effect or even inhibited the recovery of these indices. (author)

  16. Effects of drugs inhibiting prostaglandin or leukotriene biosynthesis on postirradiation haematopoiesis in mouse

    Energy Technology Data Exchange (ETDEWEB)

    Kozubik, A.; Hofmanova, J.; Pospisil, M.; Netikova, J.; Hola, J.; Lojek, A. (Ceskoslovenska Akademie Ved, Brno (Czech Republic). Biofysikalni Ustav)

    1994-03-01

    Two non-steroidal anti-inflammatory drugs, i.e. indomethacin (INDO), an inhibitor of prostaglandin production, and esculetin (ESCUL), an inhibitor of leukotriene production, were tested for their ability to modify haematopoiesis in three experimental systems: (a) in vitro clonal proliferation of marrow GM-CFC from the irradiated mouse was found to be augmented by addition of INDO at a low concentration, and inhibited by ESCUL in a dose-dependent manner; (b) in the lethally irradiated and bone marrow-transplanted mice treated with the drugs in the postirradiation period, stimulatory effects of INDO on CFU-S and GM-CFC populations and an inhibitory effect of ESCUL on GM-CFC were observed; and (c) when the drugs were administered i.p. to mice 1 h before 5-Gy irradiation, INDO enhanced the postirradiation recovery of haematopoietic indices such the numbers of CFU-S, GM-CFC, peripheral blood granuloctyes, and nucleated bone marrow cells, while ESCUL had no effect or even inhibited the recovery of these indices. (author).

  17. Search for B{r_arrow}{mu}{bar {nu}}{sub {mu}}{gamma} and B{r_arrow}e{bar {nu}}{sub e}{gamma}

    Energy Technology Data Exchange (ETDEWEB)

    Browder, T.E.; Li, F.; Li, Y.; Rodriguez, J.L. [University of Hawaii at Manoa, Honolulu, Hawaii 96822 (United States); Bergfeld, T.; Eisenstein, B.I.; Ernst, J.; Gladding, G.E.; Gollin, G.D.; Johnson, E.; Karliner, I.; Palmer, M.; Selen, M.; Thaler, J.J. [University of Illinois, Champaign-Urbana, Illinois 61801 (United States); Edwards, K.W. [Carleton University, Ottawa, Ontario, K1S 5B6 (Canada); Bellerive, A.; Britton, D.I.; Janicek, R.; MacFarlane, D.B.; McLean, K.W.; Patel, P.M. [McGill University, Montreal, Quebec, H3A 2T8 (Canada); Sadoff, A.J. [Ithaca College, Ithaca, New York 14850 (United States); Ammar, R.; Baringer, P.; Bean, A.; Besson, D.; Coppage, D.; Darling, C.; Davis, R.; Hancock, N.; Kotov, S.; Kravchenko, I.; Kwak, N. [University of Kansas, Lawrence, Kansas 66045 (United States); Anderson, S.; Kubota, Y.; Lattery, M.; ONeill, J.J.; Patton, S.; Poling, R.; Riehle, T.; Smith, A.; Savinov, V. [University of Minnesota, Minneapolis, Minnesota 55455 (United States); Alam, M.S.; Athar, S.B.; Ling, Z.; Mahmood, A.H.; Severini, H.; Timm, S.; Wappler, F. [State University of New York at Albany, Albany, New York 12222 (United States); Anastassov, A.; Blinov, S.; Duboscq, J.E.; Fulton, R.; Fujino, D.; Gan, K.K.; Hart, T.; Honscheid, K.; Kagan, H.; Kass, R.; Lee, J.; Sung, M.; Undrus, A.; Wanke, R.; Wolf, A.; Zoeller, M.M. [Ohio State University, Columbus, Ohio 43210 (United States); Nemati, B.; Richichi, S.J.; Ross, W.R.; Skubic, P.; Wood, M. [University of Oklahoma, Norman, Oklahoma 73019 (United States); Bishai, M.; Fast, J.; Gerndt, E.; Hinson, J.W.; Miller, D.H.; Shibata, E.I.; Shipsey, I.P.; Yurko, M. [Purdue University, West Lafayette, Indiana 47907 (United States); Gibbons, L.; Johnson, S.D.; Kwon, Y.; Roberts, S.; Thorndike, E.H. [University of Rochester, Rochester, New York 14627 (United States); Jessop, C.P.; Lingel, K.; Marsiske, H.; Perl, M.L.; Schaffner, S.F.; Ugolini, D.; Wang, R.; Zhou, X.; and others

    1997-07-01

    We have searched for the decays B{r_arrow}{mu}{bar {nu}}{sub {mu}}{gamma} and B{r_arrow}e{bar {nu}}{sub e}{gamma} in a sample of 2.7{times}10{sup 6} charged B decays collected with the CLEO II detector. In the muon channel, we observe no candidates in the signal region and set an upper limit on the branching fraction of B(B{r_arrow}{mu}{bar {nu}}{sub {mu}}{gamma}){lt}5.2{times}10{sup {minus}5} at the 90{percent} confidence level. In the electron channel, we observe five candidates in the signal region and set an upper limit on the branching fraction of B(B{r_arrow}e{bar {nu}}{sub e}{gamma}){lt}2.0{times}10{sup {minus}4} at the 90{percent} confidence level. {copyright} {ital 1997} {ital The American Physical Society}

  18. Antihypertensive effect of eicosapentaenoic acid (EPA) on spontaneously hypertensive rats (SHR)

    International Nuclear Information System (INIS)

    Lam, B.K.; Quilley, J.; Hirai, A.; Yoshida, S.; Tamura, Y.; Wong, P.Y.K.

    1986-01-01

    EPA ethyl ester (99.8% pure) was administered orally (300 mg/kg/d) to adult (25-wk-old) and young (11 1/2-wk-old) SHR rats for 2 weeks at which time systolic blood pressure (BP), platelet aggregation, glomerular leukotriene (LT)A 4 hydrolase activity, plasma renin activity (PRA), urinary levels of TxB 2 and 6-keto-PGF/sub 1α/ and aortic conversion of [ 14 C]-AA to [ 14 C]-6-keto-PGF/sub 1α/ were measured. EPA treatment decreased BP of adult SHR with established hypertension from 238.7 +/- 2 to 217 +/- 4 mmHg (M +/- SD, P 4 hydrolase activity was inhibited. PRA and urinary levels of TxB 2 and 6-keto-PGF/sub 1α/ were not changed. Similarly, there was no change in aortic conversion of [ 14 C]-AA to [ 14 C]-6-keto-PGF/sub 1α/ indicating that EPA treatment does not alter vascular cyclo-oxygenase activity. These results indicate that EPA treatment affects eicosanoid metabolism and cardiovascular function

  19. Neutrophil derived LTB4 induces macrophage aggregation in response to encapsulated Streptococcus iniae infection.

    Directory of Open Access Journals (Sweden)

    William J B Vincent

    Full Text Available Immune cells sense and react to a multitude of factors including both host and microbe-derived signals. Understanding how cells translate these cues into particular cellular behaviors is a complex yet critical area of study. We have previously shown that both neutrophils and macrophages are important for controlling the fish pathogen Streptococcus iniae. Here, we report both host and bacterial determinants leading to the formation of organized macrophage aggregates as part of the host inflammatory response in a subset of infected larvae. Streptococcal capsule was a required signal for aggregate formation. Macrophage aggregation coincided with NFκB activity, and the formation of these aggregates is mediated by leukotriene B4 (LTB4 produced by neutrophils. Depletion, inhibition, or genetic deletion of leukotriene A4 hydrolase (Lta4h, which catalyzes the last step in LTB4 synthesis, resulted in the absence of macrophage aggregation. Larvae with impaired neutrophil function also had impaired macrophage aggregation; however, aggregate formation was partially rescued with the addition of exogenous LTB4. Neutrophil-specific expression of lta4h was sufficient to rescue macrophage aggregation in Lta4h-deficient larvae and increased host survival following infection. In summary, our findings highlight a novel innate immune response to infection in which specific bacterial products drive neutrophils that modulate macrophage behavior through eicosanoid signaling.

  20. ltür ve Sanat Ekonomisi Kapsamında Talep Analizleri Yardımı ile Kültür Politikasına Teorik Yaklaşım: Türkiye Örneği

    Directory of Open Access Journals (Sweden)

    Duygu BÜYÜKYAZICI

    2016-08-01

    Full Text Available Kültür-sanat ekonomisinin bağımsız bir disiplin olarak ortaya çıkmasını sağlayantemel tez, devletin sanatı desteklemesi gerektiği önermesidir. Gösteri sanatı formlarınıniktisadi araçlarla incelenmesi sonucunda ortaya konan maliyet hastalığı argümanı, devletsanatları desteklemezse sanatların yok olacağı öngörüsünü içerir. Söz konusu analizlerdenönce devlet-sanat ilişkisi farklı disiplinlerin gözlem alanında iken, bu değişkenlerin yanınaekonomi teriminin eklenmesi tartışmaları bilimsel zemine çekmiş ve engin incelemeleriberaberinde getirmiştir. Devletin finansal ve kurumsal anlamda sanatı desteklemesi politikayapıcıların nezdinde erdemli mallar varsayımı ile gerçekleşirken, literatürdekitemellendirmeler büyük ölçüde piyasa başarısızlıkları ekseninde olmuş ve maliyet hastalığıargümanı çürütülmüştür. Devletin sanatı destekleme formu ve miktarına yönelik tercihlerkültür politikasının önemli payını oluştururken, söz konusu politikaların edinilmiş başarısıancak talep analizleri ile tartılabilir. Türkiye’nin kültür politikasına hem teorik biryaklaşımda bulunmayı hem de ulaşılmış başarısını araştırmayı amaçlayan buçalışmada, kültür-sanat ekonomisindeki mikroekonomik talep analizlerinden yola çıkarak,talep profilinin kültür politikasındaki önemi vurgulanmakta ve devletin kültür-sanata olandesteği kadar biçiminin öneminin de altı çizilmektedir. Talep analizlerinin gelişmesidoğrultusunda, talebin profiline yönelik farklı kültür politikaları gerekecek, kültür-sanatayönelik çoğunlukla yetersiz veri ve analiz ile tespit edilen destek, üretim vesübvansiyonların içerik ve miktarı farklılaşarak optimal düzeye yakınsanacaktır. Piyasabaşarısızlıklar da kültür politikasının temellendiği teorik faz olarak analize eklenmiş, pozitifdışsallıklar özelinde devletin sanatı desteklemesinin sebepleri

  1. Designing an efficient LT-code with unequal error protection for image transmission

    Science.gov (United States)

    S. Marques, F.; Schwartz, C.; Pinho, M. S.; Finamore, W. A.

    2015-10-01

    recommended by CCSDS. In fact, to design a LT-code with an unequal error protection, the bit stream produced by the algorithm recommended by CCSDS must be partitioned in M disjoint sets of bits. Using the weighted approach, the LT-code produces M different failure probabilities for each set of bits, p1, ..., pM leading to a total probability of failure, p which is an average of p1, ..., pM. In general, the parameters of the LT-code with unequal error protection is chosen using a heuristic procedure. In this work, we analyze the problem of choosing the LT-code parameters to optimize two figure of merits: (a) the probability of achieving a minimum acceptable PSNR, and (b) the mean of PSNR, given that the minimum acceptable PSNR has been achieved. Given the rate-distortion curve achieved by CCSDS recommended algorithm, this work establishes a closed form of the mean of PSNR (given that the minimum acceptable PSNR has been achieved) as a function of p1, ..., pM. The main contribution of this work is the study of a criteria to select the parameters p1, ..., pM to optimize the performance of image transmission.

  2. Prostaglandin (PG) E3 synthesis elicted by adrenergic stimuli in guinea-pig trachea (GPT) is mediated primarily by B2 adrenergic receptors

    Energy Technology Data Exchange (ETDEWEB)

    Nadel, G.L.; Malik, K.U.; Lew, D.B. (Univ. of Tennessee, Memphis (United States))

    1990-02-26

    The purpose of this study was to examine arachidonic acid (AA) metabolism and to characterize the type of adrenergic receptor (AR) involved in the production of the major metabolite of this fatty acid. ({sup 14}C)AA was incubated with GPT-rings and the radiolabelled products were extracted and separated by TLC method. The medium was also assayed for radiolabelled immunoreactive PG's (iPG's) and leukotrienes (LT) B4 and C4 by RIA or Enzyme immunoassay (EIA) after exposure to various AR agonists. ({sup 14}C)AA was incorporated into GPT-rings and metabolized mainly into iPGE2 and smaller amounts into PGF2{alpha}. Trace amounts of PGD2 and 6-keto-PGF1{alpha} but not LTB4 or LTC4 were detected by RIA and/or EIA. Incubation of GPT rings for 15 minutes with isoproterenol and salbutamol resulted in a significant increase of PGE2 synthesis (optimum conc: 10{sup {minus}7}, 10{sup {minus}7}M respectively). In contrast, dobutamine, norepinephrine, phenylnephrine and xylazine (up to 10{sup {minus}6}M) did not significantly increase PGE2 production. Isoproterenol-induced iPGE2 production was inhibited by a selective {beta}2 antagonist, butoxamine (70%: 10{sup {minus}7}M, 91%: 10{sup {minus}6}M) and somewhat reduced by {beta}1 antagonists practolol and metoprolol (30-64%:10{sup {minus}6}M). These data suggest that isoproterenol induced iPGE2 synthesis is primarily mediated via activation of {beta}2 adrenergic receptor.

  3. Genetic influences on ovulation of primary oocytes in LT/Sv strain mice.

    Science.gov (United States)

    Everett, Clare A; Auchincloss, Catherine A; Kaufman, Matthew H; Abbott, Catherine M; West, John D

    2004-11-01

    A high proportion of LT/Sv strain oocytes arrest in meiotic metaphase I (MI) and are ovulated as diploid primary oocytes rather than haploid secondary oocytes. (Mus musculus castaneus x LT/SvKau)F1 x LT/SvKau backcross females were analysed for the proportion of oocytes that arrested in MI and typed by PCR for a panel of microsatellite DNA sequences (simple sequence repeat polymorphisms) that differed between strain LT/SvKau and M. m. castaneus. This provided a whole genome scan of 86 genetic markers distributed over all 19 autosomes and the X chromosome, and revealed genetic linkage of the MI arrest phenotype to markers on chromosomes 1 and 9. Identification of these two chromosomal regions should facilitate the identification of genes involved in mammalian oocyte maturation and the control of meiosis.

  4. Mechanisms of aspirin-sensitive asthma

    Directory of Open Access Journals (Sweden)

    Sun Ying

    2004-01-01

    Full Text Available It is now widely accepted that aspirin, along with other non-steroidal anti-inflammatory drugs (NSAIDs, may precipitate asthma attacks in a minority of susceptible individuals. The syndrome is part of a mucosal inflammatory disease that typically affects the nasal, as well as the bronchial, mucosa and sometimes the gut and skin also. Although the mucosal cellular infiltrate in aspirin-sensitive asthma and rhinitis resembles that of asthma and rhinitis in general, there is evidence of increased expression of asthma-relevant cytokines, such as interleukin-5 and granulocyte–macrophage colony stimulating factor, and a more intense infiltrate of mast cells and eosinophils. One key feature of aspirin-sensitive asthma is thought to be the overproduction of cysteinyl leukotrienes, principally by these local mast cells and eosinophils, but whether this represents a fundamental abnormality or is simply a consequence of greater numbers and activation of inflammatory cells is unclear. Genetic polymorphisms of the leukotriene C4 synthase gene, which result in elevated expression of this enzyme, may also play a role. In addition, overexpression of cysteinyl leukotriene receptors, particularly CysLT1, may contribute to an enhanced response of local inflammatory and structural cells to cysteinyl leukotrienes. Aspirin challenge in these patients is accompanied by acute further elevation of the already elevated baseline cysteinyl leukotriene synthesis, a phenomenon that is most closely related to the ability of aspirin and related NSAIDs to inhibit the cyclooxygenase enzyme COX-1. The reason for this is unknown, although it has been suggested that the COX-1 product prostaglandin E2 (PGE2 serves as a ‘brake’ to leukotriene synthesis and that somehow this mechanism is deficient in aspirin-sensitive asthmatics. A better understanding of the pathogenesis of aspirin-sensitive asthma will undoubtedly lead to better approaches to treatment. Aside from the use of

  5. Mastering Autodesk Inventor 2015 and Autodesk Inventor LT 2015

    CERN Document Server

    Waguespack, Curtis

    2014-01-01

    A comprehensive guide to Autodesk Inventor and Inventor LT This detailed reference and tutorial provides straightforward explanations, real-world examples, and practical tutorials that focus squarely on teaching Autodesk Inventor tips, tricks, and techniques. The book also includes a project at the beginning to help those new to Inventor quickly understand key interface conventions and capabilities. In addition, there is more information on Inventor LT, new practice drawings at the end of each chapter to reinforce lessons learned, and thorough coverage of all of Inventor's new features. The au

  6. Role of the route of leukotrienes in an experimental model of oral mucositis induced by 5-fluorouracil 1.

    Science.gov (United States)

    Silva, Viviane Carvalho da; Leitão, Renata Ferreira de Carvalho; Brito, Gerly Anne de Castro; Martins, Conceição da Silva; Freire, Gildenio Estevam; Aragão, Karoline Saboia; Wanderley, Carlos Wagner de Souza; Freitas, Marcos Rabelo de

    2017-09-01

    To investigate the participation of cysteinyl leukotrienes in the pathophysiology of oral mucositis. Oral mucositis was induced in hamsters using 5-fluorouracil (5-FU; 60 and 40 mg/kg; i.p., on days 1 and 2, respectively, and with excoriations in jugal mucosa on day 4). Montelukast (10, 20, or 40 mg/kg/d; gavage), MK886 (3 mg/kg/d, i.p.), or saline or celecoxib (7.5 mg/kg/d; i.p.) was administered 1 h prior to 5-FU and daily, until the fourth (MK886) or tenth day, when the animals were euthanized and their jugal mucosa was collected for macroscopic, histopathological, and immunohistochemical evaluation. Neither montelukast nor MK-886 prevented the oral mucositis induced by 5-FU, as observed by histopathological evaluation. In addition, we did not find significant differences in the expression of inducible nitric oxide synthase-2, cyclooxygenase-2, or interleukin (IL)-1β between the experimental and control groups. However, we did observe a significant decrease in tumor necrosis factor (TNF)-α expression for all doses of montelukast; we also observed a significant decrease in IL-10 with 40 mg/kg/d and MK 886. Cysteinyl leukotrienes do not play an important role in experimental oral mucositis induced by 5-FU. There is a modulating action specifically on TNF-α.

  7. Montelukast prevents vascular endothelial dysfunction from internal combustion exhaust inhalation during exercise.

    Science.gov (United States)

    Rundell, Kenneth W; Steigerwald, Michelle D; Fisk, Michelle Z

    2010-08-01

    Associations between high particulate matter (PM) pollution and increased morbidity and mortality from coronary heart disease have been identified. This study assessed leukotriene (LT) participation in PM-induced vascular endothelial dysfunction. Ten healthy males exercised 4 times for 30 min in both high PM (550,286 +/- 42,004 particles x cm(-3)) and low PM (4571 +/- 1922 particles x cm(-3)) after ingesting placebo (PL) or 10 mg montelukast (MK; half-life 3-6 h), a leukotriene receptor antagonist. Brachial artery flow-mediated dilation (FMD) was measured pre- and 30 min, 4 h, 24 h post-exercise. No basal brachial artery vascoconstriction was evident from high PM exercise. High PM blunted FMD, whereas high PM MK, low PM PL, and low PM MK demonstrated normal FMD (p < .003). Change in FMD (pre- to post-exercise) for high PM PL was different than for high PM MK, low PM PL, and low PM MK at 30 min post-exercise (p < .007). At 4 h, high PM MK FMD blunting increased (p = .1). At 24 h, high PM FMD blunting persisted (p < .05); no difference was observed between high PM PL or MK treatment, but was different that low PM PL/MK treatments (p < .05). MK blocked high PM post-exercise FMD blunting and maintained normal response, suggesting that leukotrienes are involved in PM-initiated vascular endothelial dysfunction.

  8. Passively Q-switched mode-locked Nd3+:LuVO4 laser by LT-GaAs saturable absorber

    International Nuclear Information System (INIS)

    Li, M; Zhao, S; Li, Y; Yang, K; Li, G; Li, D; An, J; Li, T; Yu, Z

    2009-01-01

    By using LT-GaAs as saturable absorber, we have demonstrated the stable Q-switched and mode-locked (QML) Nd:LuVO 4 laser run in a Z-type folded cavity. Nearly 100% modulation depth of mode locking can be obtained as long as the pump power reaches the oscillation threshold. The repetition rate of the passively Q-switched pulse envelops ranges from 37.5 to 139 kHz as the pump power increased from 1.7 to 8.2 W. The mode-locked pulse inside the Q-switched envelop has an estimated pulse width of about 220 ps and a repetition rate of 111 MHz. Under an incident pump power of 8.2 W, the highest pulse energy of 6 μJ of each Q-switched envelope, and the highest peak power about 2.73 kW of Q-switched mode-locked pulses can be obtained

  9. Comparison Results on the Basic Phenomena between CAP and CONTEMPT-LT

    Energy Technology Data Exchange (ETDEWEB)

    Choo, Yeon Joon; Hong, Soon Joon; Hwang, Su Hyun; Kim, Min Ki; Lee, Byung Chul [FNC Tech., SNU, Seoul (Korea, Republic of); Ha, Sang Jun; Choi, Hoon [KHNP Central Research Institute, Daejeon (Korea, Republic of)

    2011-10-15

    A development project for the domestic design code was launched to be used for the safety and performance analysis of pressurized light water reactors. As a part of this project, CAP (Containment Analysis Package) code has been developing for the containment safety and performance analysis side by side with SPACE. CAP Beta version has been released lately and validation processes are under way currently. Code by code comparison activity is scheduled in the validation processes and the first comparable code is CONTEMPT-LT. CONTEMPT-LT was developed to predict the longterm behavior of water-cooled nuclear reactor containment systems subjected to postulated loss-ofcoolant accident (LOCA) conditions. CONTEMPT-LT calculates the time variation of compartment pressures, temperatures, mass and energy inventories, heat structure temperature distributions, and energy exchange with adjacent compartments, leakage on containment response. Models are provided for fan cooler and cooling spray as engineered safety systems. Any compartment may have both a liquid pool region and an air-vapor atmosphere region above the pool. Each region is assumed to have a uniform temperature, but the temperatures of the two regions may be different. As mentioned above, CONTEMP-LT has the similar code features and it, therefore, is expected to show the similar analysis performance with CAP. In this study, the code performances were compared for the same phenomena between CAP and CONTEMPT-LT. Code comparison is carried out through two stages; separate and integral effect comparison

  10. Comparison Results on the Basic Phenomena between CAP and CONTEMPT-LT

    International Nuclear Information System (INIS)

    Choo, Yeon Joon; Hong, Soon Joon; Hwang, Su Hyun; Kim, Min Ki; Lee, Byung Chul; Ha, Sang Jun; Choi, Hoon

    2011-01-01

    A development project for the domestic design code was launched to be used for the safety and performance analysis of pressurized light water reactors. As a part of this project, CAP (Containment Analysis Package) code has been developing for the containment safety and performance analysis side by side with SPACE. CAP Beta version has been released lately and validation processes are under way currently. Code by code comparison activity is scheduled in the validation processes and the first comparable code is CONTEMPT-LT. CONTEMPT-LT was developed to predict the longterm behavior of water-cooled nuclear reactor containment systems subjected to postulated loss-ofcoolant accident (LOCA) conditions. CONTEMPT-LT calculates the time variation of compartment pressures, temperatures, mass and energy inventories, heat structure temperature distributions, and energy exchange with adjacent compartments, leakage on containment response. Models are provided for fan cooler and cooling spray as engineered safety systems. Any compartment may have both a liquid pool region and an air-vapor atmosphere region above the pool. Each region is assumed to have a uniform temperature, but the temperatures of the two regions may be different. As mentioned above, CONTEMP-LT has the similar code features and it, therefore, is expected to show the similar analysis performance with CAP. In this study, the code performances were compared for the same phenomena between CAP and CONTEMPT-LT. Code comparison is carried out through two stages; separate and integral effect comparison

  11. CysLT(1)R antagonists inhibit tumor growth in a xenograft model of colon cancer.

    Science.gov (United States)

    Savari, Sayeh; Liu, Minghui; Zhang, Yuan; Sime, Wondossen; Sjölander, Anita

    2013-01-01

    The expression of the inflammatory G-protein coupled receptor CysLT1R has been shown to be upregulated in colon cancer patients and associated with poor prognosis. The present study investigated the correlation between CysLT1R and colon cancer development in vivo using CysLT1R antagonists (ZM198,615 or Montelukast) and the nude mouse xenograft model. Two drug administration regimens were established. The first regimen was established to investigate the importance of CysLT1R in tumor initiation. Nude mice were inoculated with 50 µM CysLT1R antagonist-pretreated HCT-116 colon cancer cells and received continued treatment (5 mg/kg/day, intraperitoneally). The second regimen aimed to address the role of CysLT1R in tumor progression. Nude mice were inoculated with non-pretreated HCT-116 cells and did not receive CysLT1R antagonist treatment until recordable tumor appearance. Both regimens resulted in significantly reduced tumor size, attributed to changes in proliferation and apoptosis as determined by reduced Ki-67 levels and increased levels of p21(WAF/Cip1) (Pcolon cancer cell line HCT-116 and CysLT1R antagonists. In addition to significant reductions in cell proliferation, adhesion and colony formation, we observed induction of cell cycle arrest and apoptosis in a dose-dependent manner. The ability of Montelukast to inhibit growth of human colon cancer xenograft was further validated by using two additional colon cancer cell lines, SW-480 and HT-29. Our results demonstrate that CysLT1R antagonists inhibit growth of colon cancer xenografts primarily by reducing proliferation and inducing apoptosis of the tumor cells.

  12. Diode-pumped passively mode-locked Nd:LuVO4 laser with LT-In0.25Ga0.75As saturable absorber

    International Nuclear Information System (INIS)

    Li, T; Zhao, S; Li, Y; Zhuo, Z; Yang, K; Li, G; Li, D; Yu, Z

    2009-01-01

    A diode pumped passively mode-locked Nd:LuVO 4 laser with a low temperature (LT) In 0.25 Ga 0.75 As absorber is realized in this paper. An In 0.25 Ga 0.75 As single-quantum-well absorber, which is grown by use of the metal-organic chemical-vapor deposition technique, acts as nonlinear absorber and output coupler simultaneously. A special cavity is designed to keep the power density on In 0.25 Ga 0.75 As under its damage threshold. Both the Q-switched and continuous-wave (cw) mode locking operation are experimentally realized. An average output power of 5.9 W with pulse width of 4.9 ps is achieved at the pump power of 22 W, corresponding to an optical conversion efficiency of 26.8%

  13. Human LT-alpha-mediated resistance to autoimmune diabetes is induced in NOD, but not NOD-scid, mice and abrogated by IL-12.

    Science.gov (United States)

    Miyaguchi, S; Satoh, J; Takahashi, K; Sakata, Y; Nakazawa, T; Miyazaki, J; Toyota, T

    2001-01-01

    Systemic administration of human lymphotoxin-alpha (hLT-alpha) made NOD mice resistant not only to spontaneous autoimmune type 1 diabetes mellitus but also to cyclophosphamide (CY)-induced diabetes and diabetes transfer by diabetic NOD spleen cells (triple resistance). In this study we analyzed the mechanisms of hLT-alpha-induced resistance, focusing on (1) hLT-alpha-induced resistance in the pancreatic beta cell, (2) CY-resistant suppressor cells, (3) suppression of induction or function of effector cells for beta cell destruction, or (4) others. To examine the first possibility in vitro, a NOD-derived beta cell line (MIN6N) was pretreated with hLT-alpha and then mixed with diabetic NOD spleen cells and MIN6N cell viability was measured. Treatment with hLT-alpha did not protect MIN6N cells but rather enhanced cytotoxicity. Next NOD-scid mice were pretreated with hLT-alpha and then transferred with diabetic NOD spleen. All the recipients developed diabetes. These results excluded the first possibility. The second possibility was also excluded by a cotransfer experiment, in which diabetic NOD spleen cells were cotransferred to NOD-scid mice with nontreated or hLT-alpha-treated nondiabetic NOD spleens. There was no significant difference in diabetes incidence between the two groups. To observe the third possibility, spleen cells of hLT-alpha-treated triple-resistant NOD mice were transferred to NOD-scid mice. Diabetes developed in the recipients, although the onset of diabetes was slightly delayed. Finally, hLT-alpha-treated triple-resistant NOD mice developed diabetes 1 week after daily IL-12 treatment. In summary, hLT-alpha administration made NOD mice resistant to effector cells for beta cell destruction. This resistance was induced in NOD, but not in NOD-scid, mice, indicating that lymphocytes were obligatory for the resistance. However, it was not mediated by transferable suppressor cells. Because effector cells were present in hLT-alpha-treated NOD spleen and

  14. A randomized trial of montelukast in respiratory syncytial virus postbronchiolitis

    DEFF Research Database (Denmark)

    Bisgaard, Hans

    2003-01-01

    Infants often develop reactive airway disease after respiratory syncytial virus (RSV) bronchiolitis. Cysteinyl-leukotrienes (cys-LT) are released during RSV infection and may contribute to the inflammation. We hypothesized that a cys-LT receptor antagonist would ameliorate reactive airway disease...... subsequent to RSV bronchiolitis. One hundred and thirty infants who were 3 to 36 months old, hospitalized with acute RSV bronchiolitis, were randomized into a double-blind, parallel comparison of 5-mg montelukast chewable tablets or matching placebo given for 28 days starting within 7 days of symptom debut...

  15. The bottomside parameters B0, B1 obtained from incoherent scatter measurements during a solar maximum and their comparisons with the IRI-2001 model

    Directory of Open Access Journals (Sweden)

    N. K. Sethi

    2002-06-01

    Full Text Available High resolution electron density profiles (Ne measured with the Arecibo (18.4 N, 66.7 W, Incoherent Scatter radar (I. S. are used to obtain the bottomside shape parameters B0, B1 for a solar maximum period (1989–90. Median values of these parameters are compared with those obtained from the IRI-2001 model. It is observed that during summer, the IRI values agree fairly well with the Arecibo values, though the numbers are somewhat larger during the daytime. Discrepancies occur during winter and equinox, when the IRI underestimates B0 for the local times from about 12:00 LT to about 20:00 LT. Furthermore, the IRI model tends to generally overestimate B1 at all local times. At Arecibo, B0 increases by about 50%, and B1 decreases by about 30% from solar minimum to solar maximum.Key words. Ionosphere (equational ionosphere; modeling and forecasting

  16. Simulation-Based e-Learning Tools for Science,Engineering, and Technology Education(SimBeLT)

    Science.gov (United States)

    Davis, Doyle V.; Cherner, Y.

    2006-12-01

    The focus of Project SimBeLT is the research, development, testing, and dissemination of a new type of simulation-based integrated e-learning set of modules for two-year college technical and engineering curricula in the areas of thermodynamics, fluid physics, and fiber optics that can also be used in secondary schools and four-year colleges. A collection of sophisticated virtual labs is the core component of the SimBeLT modules. These labs will be designed to enhance the understanding of technical concepts and underlying fundamental principles of these topics, as well as to master certain performance based skills online. SimBeLT software will help educators to meet the National Science Education Standard that "learning science and technology is something that students do, not something that is done to them". A major component of Project SimBeLT is the development of multi-layered technology-oriented virtual labs that realistically mimic workplace-like environments. Dynamic data exchange between simulations will be implemented and links with instant instructional messages and data handling tools will be realized. A second important goal of Project SimBeLT labs is to bridge technical skills and scientific knowledge by enhancing the teaching and learning of specific scientific or engineering subjects. SimBeLT builds upon research and outcomes of interactive teaching strategies and tools developed through prior NSF funding (http://webphysics.nhctc.edu/compact/index.html) (Project SimBeLT is partially supported by a grant from the National Science Foundation DUE-0603277)

  17. AutoCAD 2015 and AutoCAD LT 2015 bible

    CERN Document Server

    Finkelstein, Ellen

    2014-01-01

    The perfect reference for all AutoCAD users AutoCAD 2015 and AutoCAD LT 2015 Bible is the book you want to have close at hand to answer those day-to-day questions about this industry-leading software. Author and Autodesk University instructor Ellen Finkelstein guides readers through AutoCAD 2015 and AutoCAD LT 2015 with clear, easy-to-understand instruction and hands-on tutorials that allow even total beginners to create a design on their very first day. Although simple and fundamental enough to be used by those new to CAD, the book is so comprehensive that even Autodesk power u

  18. UEP LT Codes with Intermediate Feedback

    DEFF Research Database (Denmark)

    Sørensen, Jesper Hemming; Popovski, Petar; Østergaard, Jan

    2013-01-01

    We analyze a class of rateless codes, called Luby transform (LT) codes with unequal error protection (UEP). We show that while these codes successfully provide UEP, there is a significant price in terms of redundancy in the lower prioritized segments. We propose a modification with a single inter...... intermediate feedback message. Our analysis shows a dramatic improvement on the decoding performance of the lower prioritized segment....

  19. Marker-Assisted Selection of Xa21 Conferring Resistance to Bacterial Leaf Blight in indica Rice Cultivar LT2

    Institute of Scientific and Technical Information of China (English)

    Hue Thi NGUYEN; Trung Nguyen DINH; Nakano TOSHITSUGU; Liet Van VU; Quang Hong VU; Tan Van MAI; Thu Thi NGUYEN; Lam Duc VU; Tung Thanh NGUYEN; Long Viet NGUYEN; Hien Thu Thi VU; Hue Thi NONG

    2018-01-01

    Bacterial leaf blight of rice (BLB), caused by Xanthomonas oryzae pv. oryzae, is one of the most destructive diseases in Asian rice fields. A high-quality rice variety, LT2, was used as the recipient parent. IRBB21, which carries the Xa21 gene, was used as the donor parent. The resistance gene Xa21 was introduced into LT2 by marker-assisted backcrossing. Three Xoo races were used to inoculate the improved lines following the clipping method. Eleven BC3F3lines carrying Xa21 were obtained based on molecular markers and agronomic performance. The 11 lines were then inoculated with the three Xoo races. All the 11 improved lines showed better resistance to BLB than the recipient parent LT2. Based on the level of resistance to BLB and their agronomic performance, five lines (BC3F35.1.5.1, BC3F35.1.5.12, BC3F38.5.6.44, BC3F3 9.5.4.1 and BC3F39.5.4.23) were selected as the most promising for commercial release. These improved lines could contribute to rice production in terms of food security.

  20. Low temperature solid oxide electrolytes (LT-SOE): A review

    Science.gov (United States)

    Singh, B.; Ghosh, S.; Aich, S.; Roy, B.

    2017-01-01

    Low temperature solid oxide fuel cell (LT-SOFC) can be a source of power for vehicles, online grid, and at the same time reduce system cost, offer high reliability, and fast start-up. A huge amount of research work, as evident from the literature has been conducted for the enhancement of the ionic conductivity of LT electrolytes in the last few years. The basic conduction mechanisms, advantages and disadvantages of different LT oxide ion conducting electrolytes {BIMEVOX systems, bilayer systems including doped cerium oxide/stabilised bismuth oxide and YSZ/DCO}, mixed ion conducting electrolytes {doped cerium oxides/alkali metal carbonate composites}, and proton conducting electrolytes {doped and undoped BaCeO3, BaZrO3, etc.} are discussed here based on the recent research articles. Effect of various material aspects (composition, doping, layer thickness, etc.), fabrication methods (to achieve different microstructures and particle size), design related strategies (interlayer, sintering aid etc.), characterization temperature & environment on the conductivity of the electrolytes and performance of the fuel cells made from these electrolytes are shown in tabular form and discussed. The conductivity of the electrolytes and performance of the corresponding fuel cells are compared. Other applications of the electrolytes are mentioned. A few considerations regarding the future prospects are pointed.

  1. Identification and characterization of luekotriene C4 and D4 receptors on a cultured smooth muscle cell line, BC3H-1

    International Nuclear Information System (INIS)

    Tamura, N.; Agrawal, D.K.; Townley, R.G.

    1987-01-01

    The authors studied the characteristics of the leukotriene (LT) C 4 and D 4 receptors on a cultured smooth muscle cell line, BC3H-1. Specific [ 3 H]LTC 4 binding to the cell membrane was greater than 80% of total binding and saturable at a density of 3.96 +/- 0.39 pmol/mg protein, with an apparent dissociation constant(Kd) of 14.3 +/- 2.0 nM (n=9). The association and dissociation of [ 3 H]LTC 4 binding were rapid and apparent equilibrium conditions were established within 5 min. Calculated Kd value of [ 3 H]LTC binding from the kinetic analysis was 9.9 nM. From the competition analysis, calculated Ki value of unlabeled LTC 4 to compete for the specific binding of [ 3 H]LTC 4 was 9.2 nM and was in good agreement with the Kd value obtained from the Scatchard plots or kinetic analysis. The maximum number of binding sites (Bmax) of [ 3 H]LTD 4 in the membrane of BC3H-1 cell line was about 11 times lower than that of the [ 3 H]LTC 4 . The calculated values of Kd and Bmax of [ 3 H]LTD 4 binding were 9.3 +/- 0.8 nM and 0.37 +/- 0.04 pmol/mg proteins, respectively (n=3). These findings demonstrate that BC3H-1 cell line possess both LTC 4 and LTD 4 receptors with a predominance of LTC 4 receptors. Thus, BC3H-1 cell line is a good model to study the regulation of LTC 4 and LTD 4 receptors. 34 references, 5 figures, 1 table

  2. Immunomagnetic molecular probe with UHPLC-MS/MS: A promising way for reliable bronchial asthma diagnostics based on quantification of cysteinyl leukotrienes

    Czech Academy of Sciences Publication Activity Database

    Syslová, K.; Boehmová, A.; Demirbag, E.; Šimková, K.; Kuzma, Marek; Pelclová, D.; Sedlák, V.; Čáp, P.; Martásek, P.; Kačer, P.

    81-82, AUG 2013 (2013), s. 108-117 ISSN 0731-7085 Institutional support: RVO:61388971 Keywords : Cysteinyl leukotrienes * Immunomagnetic separation * UHPLC-MS Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 2.829, year: 2013

  3. LT COL F.F. PIENAAR'S BOER WAR DIARY

    African Journals Online (AJOL)

    LT COL F.F. PIENAAR'S BOER WAR DIARY. (PART II). Brig J.H. Picard, SM*. FREE STATE TO ..... bing up and down on his master's spare horse. ... Jantjie and his master turned out of the road, and ..... on a list which burghers could afford to.

  4. Marker-Assisted Selection of Xa21 Conferring Resistance to Bacterial Leaf Blight in indica Rice Cultivar LT2

    Directory of Open Access Journals (Sweden)

    Hue Thi Nguyen

    2018-01-01

    Full Text Available Bacterial leaf blight of rice (BLB, caused by Xanthomonas oryzae pv. oryzae, is one of the most destructive diseases in Asian rice fields. A high-quality rice variety, LT2, was used as the recipient parent. IRBB21, which carries the Xa21 gene, was used as the donor parent. The resistance gene Xa21 was introduced into LT2 by marker-assisted backcrossing. Three Xoo races were used to inoculate the improved lines following the clipping method. Eleven BC3F3 lines carrying Xa21 were obtained based on molecular markers and agronomic performance. The 11 lines were then inoculated with the three Xoo races. All the 11 improved lines showed better resistance to BLB than the recipient parent LT2. Based on the level of resistance to BLB and their agronomic performance, five lines (BC3F3 5.1.5.1, BC3F3 5.1.5.12, BC3F3 8.5.6.44, BC3F3 9.5.4.1 and BC3F3 9.5.4.23 were selected as the most promising for commercial release. These improved lines could contribute to rice production in terms of food security.

  5. Persistence of Salmonella Typhimurium LT2 in Soil Enhanced after Growth in Lettuce Medium

    Directory of Open Access Journals (Sweden)

    Kornelia Smalla

    2017-04-01

    Full Text Available The persistence of Salmonella in the environment is influenced by a multitude of biotic and abiotic factors. In addition, its persistence can be influenced by preadaptation before the introduction into the environment. In order to study how preadaptation changes the survival of Salmonella in soil and therefore its potential to colonize the phytosphere, we developed a new medium based on lettuce material [lettuce medium (LM]. Salmonella enterica serovar Typhimurium strain LT2 was used as a model for Salmonella in this study. LT2 was inoculated into soil microcosms after pregrowth in Luria Bertani (LB broth or in LM. Survival of LT2 in soil was monitored over 56 days by plate counts and quantification of the Typhimurium-specific gene STM4497 using qPCR in total community DNA for which primers and TaqMan probe were designed in this study. Significantly enhanced persistence was observed for LT2 pregrown in LM compared to LT2 pregrown in LB, indicating a preadaptation effect. Surprisingly, no improved survival could be observed for S. Typhimurium strain 14028s and S. enterica serovar Senftenberg after pregrowth on LM. This indicates a high strain specificity of preadaptation. Results from previous studies suggested that biofilm formation could enhance the survival of human pathogens in various environments and might contribute to enhanced survival on plants. In vitro biofilm assays with several Salmonella strains revealed a strain-specific effect of LM on the biofilm formation. While LM significantly improved the biofilm formation of S. Senftenberg, the biofilm formation of LT2 was better in LB. This indicates that the better survival of LM-pregrown LT2 in soil was not linked to an improved ability to form biofilms but was likely due to other factors. Most importantly, this study showed that the medium used to pregrow Salmonella can influence its survival in soil and its biofilm formation which might influence the fate of Salmonella in soil.

  6. Urinary metabolites of histamine and leukotrienes before and after placebo-controlled challenge with ASA and food additives in chronic urticaria patients.

    Science.gov (United States)

    Di Lorenzo, G; Pacor, M L; Vignola, A M; Profita, M; Esposito-Pellitteri, M; Biasi, D; Corrocher, R; Caruso, C

    2002-12-01

    The recovery of mediator metabolites from urine has the potential to provide a rapid, safe, and easily available index of release of mediators. We aimed to determine urinary metabolites of both histamine and leukotrienes (LTs) in patients affected by chronic urticaria (CU). Twenty patients with CU were studied. They were selected on the basis of double-blind placebo-controlled challenge (DBPC) with acetyl salicylic acid (ASA) and food additives. Ten patients (group B) were negative to both challenges. Ten patients (group C) presented urticaria and/or the appearance of angioedema during or 24 h after challenge, with reactions to ASA (five patients) or food additives (five patients). We recruited 15 healthy volunteers as controls (group A). During a second challenge, groups B and C were challenged double-blind with a single dose of ASA, or a specific food additive, or placebo. The healthy group was challenged only with a placebo (talc capsule). Patients in groups B and C were challenged twice: with placebo (as groups B1 and C1) and with ASA (groups B2 and C2) or food additives (C2). Four samples of urine were collected; one during the night before the specific or sham challenge (baseline), and three at 2, 6 and 24 h after the challenge. Urinary methylhistamine (N-MH) and LTE4 were analyzed and normalized for urinary creatinine. For urinary N-MH at baseline, there was a significant difference only between group A and groups B1, B2, C1 and C2 (A vs. B1, P < 0.0001; A vs. B2, P < 0.0001; A vs. C1, P < 0.0001; A vs. C2, P < 0.0001). We detected a significant variation in urinary methylhistamine excretion only in group C2 after 2 h, 6 h and 24 h (P < 0.0001). However, no variations were observed in N-MH excretion rate in the other groups (A, B1, C1) after challenge with placebo, and in B2 after challenge with ASA 20 mg. For urinary LTE4 at baseline no differences were found between the mean values for the different groups. After specific challenge, only C2 patients showed

  7. Structural characterization of the Salmonella typhimurium LT2 umu operon

    International Nuclear Information System (INIS)

    Thomas, S.M.; Crowne, H.M.; Pidsley, S.C.; Sedgwick, S.G.

    1990-01-01

    The umuDC operon of Escherichia coli encodes functions required for mutagenesis induced by radiation and a wide variety of chemicals. The closely related organism Salmonella typhimurium is markedly less mutable than E. coli, but a umu homolog has recently been identified and cloned from the LT2 subline. In this study the nucleotide sequence and structure of the S. typhimurium LT2 umu operon have been determined and its gene products have been identified so that the molecular basis of umu activity might be understood more fully. S. typhimurium LT2 umu consists of a smaller 417-base-pair (bp) umuD gene ending 2 bp upstream of a larger 1,266-bp umuC gene. The only apparent structural difference between the two operons is the lack of gene overlap. An SOS box identical to that found in E. coli is present in the promoter region upstream of umuD. The calculated molecular masses of the umuD and umuC gene products were 15.3 and 47.8 kilodaltons, respectively, which agree with figures determined by transpositional disruption and maxicell analysis. The S. typhimurium and E. coli umuD sequences were 68% homologous and encoded products with 71% amino acid identity; the umuC sequences were 71% homologous and encoded products with 83% amino acid identity. Furthermore, the potential UmuD cleavage site and associated catalytic sites could be identified. Thus the very different mutagenic responses of S. typhimurium LT2 and E. coli cannot be accounted for by gross differences in operon structure or gene products. Rather, the ability of the cloned S. typhimurium umuD gene to give stronger complementation of E. coli umuD77 mutants in the absence of a functional umuC gene suggests that Salmonella UmuC protein normally constrains UmuD protein activity

  8. Ripple design of LT codes for AWGN channel

    DEFF Research Database (Denmark)

    Sørensen, Jesper Hemming; Koike-Akino, Toshiaki; Orlik, Philip

    2012-01-01

    In this paper, we present an analytical framework for designing LT codes in additive white Gaussian noise (AWGN) channels. We show that some of analytical results from binary erasure channels (BEC) also hold in AWGN channels with slight modifications. This enables us to apply a ripple-based design...

  9. ’When You Get a Job to Do, Do It.’ The Airpower Leadership of Lt Gen William H. Tunner

    Science.gov (United States)

    2008-01-01

    PAGE unclassified Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 Air University Stephen R. Lorenz, Lt Gen, Commander Air Force Doctrine...Collier, Richard. Bridge across the Sky. New York: Mc Graw - Hill, 1978. Combined Airlift Task Force. A Report on the Airlift Berlin Mis- sion. 572.101B, 26

  10. Containment pressure analysis model using CONTEMPT-LT

    International Nuclear Information System (INIS)

    Gupta, R.N.

    1975-09-01

    An analytical model for evaluating the reactor containment pressure transient following a loss-of-coolant accident (LOCA) is presented. The model uses the CONTEMPT-LT computer program developed by Aerojet Nuclear Company. The sample problem studied is the containment response following the most severe postulated LOCA at the Yankee Rowe Nuclear Power Station. The results show good agreement with the response predicted by Westinghouse Electric Corporation. (auth)

  11. Study on characterization of interaction layer between U-10wt%Mo alloy and LT24Al

    International Nuclear Information System (INIS)

    Chen Jiangang; Yin Changgeng; Sun Changlong; Pang Xiaoxuan; Liu Yunming

    2009-01-01

    The characterization of interaction layer(IL) between U-10wt%Mo alloy and LT24 Al was studied in detail in this paper. Sandwich structured U-Mo/LT24 Al diffusion couples were hot pressed at different temperature and pressure for different time. Then they were analyzed by Optical Microscope (OM) and Scanning Electron Microscope (SEM) to observe the width of the IL. The distribution of the diffusion elements and the phases in the IL were determined by Energy Dispersive Spectroscopy (EDS) and X Ray Diffraction (XRD). Analysis results are as follows: the diffusion manner was reaction diffusion, and diffusion direction mainly was that Al atoms diffused to U-Mo alloy; diffusion mechanism was vacancy diffusion and growth kinetics showed reaction was controlled by the diffusion speed; the IL containing single phase was constituted mainly by (U, Mo) Al 3 ; the IL containing two phases or more was constituted mainly by (U, Mo) Al 3 and (U, Mo) Al 4 and Al 20 Mo 2 U; and Si impurity in the LT24 Al was easy to enrich in the IL which showed Si added to Al could play positive role on improve compatibility between U-Mo and Al. (authors)

  12. MicroRNA profiling of primary cutaneous large B-cell lymphomas.

    Directory of Open Access Journals (Sweden)

    Lianne Koens

    Full Text Available Aberrant expression of microRNAs is widely accepted to be pathogenetically involved in nodal diffuse large B-cell lymphomas (DLBCLs. However, the microRNAs profiles of primary cutaneous large B-cell lymphomas (PCLBCLs are not yet described. Its two main subtypes, i.e., primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL-LT and primary cutaneous follicle center lymphoma (PCFCL are characterized by an activated B-cell (ABC-genotype and a germinal center B-cell (GCB-genotype, respectively. We performed high-throughput sequencing analysis on frozen tumor biopsies from 19 cases of PCFCL and PCLBCL-LT to establish microRNA profiles. Cluster analysis of the complete microRNome could not distinguish between the two subtypes, but 16 single microRNAs were found to be differentially expressed. Single microRNA RT-qPCR was conducted on formalin-fixed paraffin-embedded tumor biopsies of 20 additional cases, confirming higher expression of miR-9-5p, miR-31-5p, miR-129-2-3p and miR-214-3p in PCFCL as compared to PCLBCL-LT. MicroRNAs previously described to be higher expressed in ABC-type as compared to GCB-type nodal DLBCL were not differentially expressed between PCFCL and PCLBCL-LT. In conclusion, PCFCL and PCLBCL-LT differ in their microRNA profiles. In contrast to their gene expression profile, they only show slight resemblance with the microRNA profiles found in GCB- and ABC-type nodal DLBCL.

  13. The Antiaircraft Journal. Volume 97, Number 4, July-August 1954

    Science.gov (United States)

    1954-08-01

    Col. Wood- row L. Nelson, Executive; Major Harry E. Bock, Jr., S2 and S3; Capt. Jesse N. Worsham, TI&E Officer; Lt. Bernard E. Reiter, Assistant S3; Lt...Major William J. Fling, S4, leaves for Hq. Fifth Army in July; Major Alfred H. Fierke, S2, for the 17th AAA Group; Major Bernard A. Gilman, for .USAR...USAFFE. {:onerly, U. E., to 758th FA Bn., Ft. Bragg. Cornwell , B. R., to AA&GM Qr., Ft. Bliss. Crews, D. J., to USAR Adv. Gp., Rock Islane, Illinois

  14. Variability of Two Young L/T Transition Brown Dwarfs

    Science.gov (United States)

    Allers, Katelyn; Biller, Beth; Gallimore, Jack; Crossfield, Ian

    2015-10-01

    We propose for photometric monitoring observations of WISEP J004701.06+680352 (hereinafter W0047) and 2MASSWJ2244316+204343 (hereinafter 2M2244) using Spitzer/IRAC. Both objects are kinematically confirmed L7 members of the 150 Myr old AB Doradus moving group and show remarkable spectral similarity in both the near-IR and optical. The WoW survey found that L/T transition brown dwarfs having detected mid-IR variability are redder than the typical J - K color for their spectral type. A Cycle 11 exploration program (P.I. Metchev) is investigating the geometrical dependence of color and variability by expanding the original WoW sample. If inclination and J - K color are correlated (as predicted by Metchev et al.), then the spectral and photometric diversity seen across the L/T transition could be explained by geometry rather than diversity in atmospheric chemistry and dynamics. This would have wide ranging implications for the way we model cloud dissipation for brown dwarfs and extrasolar planets. Our proposed observations will provide an important test of the Metchev et al. prediction complementary to their Cycle 11 program. W0047 and 2M2244 are the same age, and have remarkably similar colors (J - K = 2.55 and 2.46 mags, respectively) and underlying spectra. Thus, if Metchev's prediction about the correlation of inclination and spectral morphology holds true, we would expect that W0047 and 2M2244 should have similar inclinations. However, the measured v sin(i) values for W0047 and 2M2244 are quite different. This difference in v sin(i) could be due to spin-axis inclination (with W0047 having a smaller i) or orbital period (with W0047 having a longer period), both of which we will determine from our proposed observations. This test is a unique opportunity, as there are no other free-floating L/T transition dwarfs known to be both coeval and spectrally similar. Our proposed observations will also extend the spectral type range for young objects surveyed for variability

  15. Inducible pathway is required for mutagenesis in Salmonella typhimurium LT2

    International Nuclear Information System (INIS)

    Orrego, C.; Eisenstadt, E.

    1987-01-01

    UV mutability of Salmonella typhimurium LT2 was eliminated in the presence of a multicopy plasmid carrying the Escherichia coli lexA + gene. This result suggests that inducible, SOS-like functions are required for UV mutagenesis in S. typhimurium. S. typhimurium strains carrying either point or deletion mutations in topA had previously been shown to lose their mutability by UV or methyl methanesulfonate. Mitomycin C induction of the Phi(mucB'-lacZ') fusion (a DNA damage-inducible locus carried on plasmid pSE205) in S. typhimurium topA was normal, suggesting that RecA is activated in topA mutants. These observations lead the authors deduce that S. typhimurium has at least one DNA damage-inducible locus in addition to recA that is required for UV mutability

  16. Corrections and additions to CONTEMPT-LT computer codes for containment analysis

    International Nuclear Information System (INIS)

    Eerikaeinen, Lauri.

    1980-01-01

    The report presents a new version of CONTEMPT-LT/26 tainment code. The corrections and additions are applicable also to other CONTEMPT-LT versions. Thermodynamical background of corrections are shortly described, and in addition, some essential points which should be taken into account in the analysis of a pressure suppression containment have been pointed out. The results obtained by the corrected version have been compared to those calculated by the original program, and to the measured data in the Marviken containment experiment No 10. Finally, it has been indicated that for reliable pressure suppression analysis a wide ranging condensation model for air-steam mixture is necessary. (author)

  17. Thermoelastic properties of ScB2, TiB2, YB4 and HoB4

    DEFF Research Database (Denmark)

    Waskowska, A.; Gerward, L.; Staun Olsen, J.

    2011-01-01

    (4)GPa). No pressure-induced phase transformations are observed in any of the above borides up to about 20GPa. A continuous temperature-driven orthorhombic distortion is observed for HoB4 below 285K. Values of the thermal expansion coefficient are reported for ScB2 and HoB4 at 293, 200 and 100K...

  18. Urinary leukotriene E(4), eosinophil protein X, and nasal eosinophil cationic protein are not associated with respiratory symptoms in 1-year-old children.

    Science.gov (United States)

    Wojnarowski, C; Halmerbauer, G; Mayatepek, E; Gartner, C; Frischer, T; Forster, J; Kuehr, J

    2001-09-01

    Eosinophilic airways inflammation forms the pathophysiologic basis for a proportion of children at risk of developing recurrent wheezing. Early preventive measures and/or anti-inflammatory treatment may be guided by the identification of such children. We aimed to study the relationship between respiratory symptoms and indirect markers of airway inflammation. We measured eosinophil protein X (EPX) and leukotriene E(4) (LTE(4)) in urine, as well as eosinophil cationic protein (ECP) in nasal lavages, in a random sample of 1-year-old children with a family history of atopy who participated in an international multicenter study on the prevention of allergy in Europe. For urine analyses, 10 children with upper respiratory illness and 19 healthy children without a family history of atopy were also enrolled. Endogenous urinary LTE(4) was separated by HPLC and determined by enzyme immunoassay with a specific antibody. The concentrations of nasal ECP and urinary EPX were determined by RIA analysis. One hundred and ten children (mean age: 1.05+/-0.1 years) were enrolled. Prolonged coughing during the first year of life was reported in 29 children, wheezy breathing in 17 children, and dry skin in 33 children. A doctor's diagnosis of wheezy bronchitis was given to 17 children. Sensitization to dust mites (specific IgE > or =1.43 ML/units) was detected in two children. Children with a doctor's diagnosis of atopic dermatitis within the first 12 months of life (n=6) had significantly higher urinary EPX than children without this (66.7 vs 30.1 microg/mmol creatinine, P=0.01). Urinary excretion of EPX and LTE4 showed a weak correlation (r=0.22, P=0.02). There were no significant differences in urinary excretion of EPX and LTE(4) or nasal ECP between children with and without respiratory symptoms (P>0.1). At the age of 1 year, urinary EPX is increased in children with atopic dermatitis. With regard to respiratory symptoms, urinary and nasal inflammatory parameters are not helpful in

  19. Interleukin-8 and eicosanoid production in the lung during moderate to severe Pneumocystis carinii pneumonia in AIDS: a role of interleukin-8 in the pathogenesis of P. carinii pneumonia

    DEFF Research Database (Denmark)

    Benfield, T L; van Steenwijk, R; Nielsen, T L

    1995-01-01

    (PG) and leukotrienes (LT)] are pro-inflammatory mediators released from arachidonic acid by action of phospholipase A2 (PLA2) and have been implicated in the host response to micro-organisms. Bronchoalveolar lavage (BAL) was performed on patients with PCP as part of a randomized study of adjuvant...... of IL-8 as a mediator in the pathogenesis of PCP, whereas the role of eicosanoids seems less clear....

  20. Clinical evaluation of leukotriene receptor antagonists in preventing common cold-like symptoms in bronchial asthma patients.

    Science.gov (United States)

    Horiguchi, Takahiko; Ohira, Daisuke; Kobayashi, Kashin; Hirose, Masahiro; Miyazaki, Junichi; Kondo, Rieko; Tachikawa, Soichi

    2007-09-01

    We investigated the possibility of preventing common cold-like symptoms as a previously unknown benefit of leukotriene receptor antagonists (LTRAs). A total of 279 adult patients with bronchial asthma referred to our hospital between June and December 2004 were retrospectively analyzed. Patients were divided into LTRA treated and untreated groups. Frequency of acute exacerbations and number of visits to emergency rooms and of hospital admissions were analyzed as indicators of frequency of infections and asthma exacerbation over the previous 12 months. Irrespective of inhaled corticosteroid (ICS) use, frequency of infections was significantly lower in the LTRA treated group (0.3 +/- 0.7 times/year) than in the LTRA untreated group (1.6 +/- 4.2 times/year) (P cold-like symptoms. Frequency of acute exacerbations and number of hospital admissions were significantly lower in the LTRA treated versus LTRA untreated group (0.4 +/- 0.8 versus 2.7 +/- 4.3 times/year and 0.0 +/- 0.2 versus 0.4 +/- 0.7 times/year, respectively; both P cold-like symptoms than those not receiving LTRAs. LTRAs play an important role in reducing the incidence of common cold-like symptoms among asthma patients and in suppressing exacerbation of asthma symptoms possibly associated with these symptoms.

  1. Quantum-well exciton dipolar interaction: Polarization-dependence and Z-LT splitting

    International Nuclear Information System (INIS)

    Nguyen Ba An.

    1996-12-01

    We calculate the exciton dipolar interaction in a semiconductor quantum well. The explicit polarization-dependence, i.e, the dependence on both the exciton dipole moment μ-vector and its inplane wavevector k-vector is derived. The obtained results for the three modes (L, T and Z modes) of the long-range part of the dipolar interaction satisfy the polarization sum rule for any parameters. In the long wavelength limit there is a Z-LT splitting which decreases as the well width increases reflecting a crossover from strict 2D to quasi-2D. A rough crossover from quasi-2D to 3D is also described. (author). 18 refs, 4 figs

  2. Lipoxin Inhibits Fungal Uptake by Macrophages and Reduces the Severity of Acute Pulmonary Infection Caused by Paracoccidioides brasiliensis

    Directory of Open Access Journals (Sweden)

    Laura R. R. Ribeiro

    2015-01-01

    Full Text Available Cysteinyl leukotrienes (CysLTs and lipoxins (LXs are lipid mediators that control inflammation, with the former inducing and the latter inhibiting this process. Because the role played by these mediators in paracoccidioidomycosis was not investigated, we aimed to characterize the role of CysLT in the pulmonary infection developed by resistant (A/J and susceptible (B10.A mice. 48 h after infection, elevated levels of pulmonary LTC4 and LXA4 were produced by both mouse strains, but higher levels were found in the lungs of susceptible mice. Blocking the CysLTs receptor by MTL reduced fungal loads in B10.A, but not in A/J mice. In susceptible mice, MLT treatment led to reduced influx of PMN leukocytes, increased recruitment of monocytes, predominant synthesis of anti-inflammatory cytokines, and augmented expression of 5- and 15-lipoxygenase mRNA, suggesting a prevalent LXA4 activity. In agreement, MTL-treated macrophages showed reduced fungal burdens associated with decreased ingestion of fungal cells. Furthermore, the addition of exogenous LX reduced, and the specific blockade of the LX receptor increased the fungal loads of B10.A macrophages. This study showed for the first time that inhibition of CysLTs signaling results in less severe pulmonary paracoccidioidomycosis that occurs in parallel with elevated LX activity and reduced infection of macrophages.

  3. Potential probiotic of Lactobacillus johnsonii LT171 for chicken ...

    African Journals Online (AJOL)

    The objective of this research was to investigate the potential probiotic of Lactobacillus johnsonii LT171. It had aggregation (60 min) and antibacterial effects against Salmonella Enteritidis, Salmonella Typhimurium and Escherichia coli O78:K80. It showed amylase and protease activity and high clear zone in culture medium ...

  4. Investigation of Public Charging Infrastructure : Case study Gränby sportfält

    OpenAIRE

    Dahl, Emma; Hedström, Andreas; Lindgren, Anna

    2017-01-01

    The municipal company Sportfastigheter AB is currently renovating and developing Gränby sportfält, a sports field in Uppsala. Adjacent to the sports field, a parking lot for 700 vehicles is located, where Sportfastigheter AB is preparing to install charging points for electric vehicles (EVs) at some of the places. This bachelor thesis aims to investigate how a public charging solution should be modeled, with the parking lot at Gränby sportfält as a case study. The investigation involves estim...

  5. Scale-up operations of CuSOB4B-NaB2BSOB4B electrolytic ...

    African Journals Online (AJOL)

    Scale-up techniques were established for an Inclined Cathode Electrochemical Cell (ICEC) for the removal of copper ions from a CuSOB4B-NaB2BSOB4B solution at reduced operation power consumption. The scale-up relationshi-ps were derived and applied in conjunction with scale-up factors. With a scale-up factor of 2, ...

  6. First measurement of the rate for the inclusive radiative penguin decay {ital b}{r_arrow}{ital s}{gamma}

    Energy Technology Data Exchange (ETDEWEB)

    Alam, M.S.; Kim, I.J.; Ling, Z.; Mahmood, A.H.; O`Neill, J.J.; Severini, H.; Sun, C.R.; Wappler, F.; Crawford, G.; Daubenmier, C.M.; Fulton, R.; Fujino, D.; Gan, K.K.; Honscheid, K.; Kagan, H.; Kass, R.; Lee, J.; Sung, M.; White, C.; Wolf, A.; Zoeller, M.M.; Butler, F.; Fu, X.; Nemati, B.; Ross, W.R.; Skubic, P.; Wood, M.; Bishai, M.; Fast, J.; Gerndt, E.; Hinson, J.W.; McIlwain, R.L.; Miao, T.; Miller, D.H.; Modesitt, M.; Payne, D.; Shibata, E.I.; Shipsey, I.P.J.; Wang, P.N.; Battle, M.; Ernst, J.; Gibbons, L.; Kwon, Y.; Roberts, S.; Thorndike, E.H.; Wang, C.H.; Coan, T.; Dominick, J.; Fadeyev, V.; Korolkov, I.; Lambrecht, M.; Sanghera, S.; Shelkov, V.; Skwarnicki, T.; Stroynowski, R.; Volobouev, I.; Wei, G.; Artuso, M.; Gao, M.; Goldberg, M.; He, D.; Horwitz, N.; Moneti, G.C.; Mountain, R.; Muheim, F.; Mukhin, Y.; Playfer, S.; Rozen, Y.; Stone, S.; Xing, X.; Zhu, G.; Bartelt, J.; Csorna, S.E.; Egyed, Z.; Jain, V.; Gibaut, D.; Kinoshita, K.; Pomianowski, P.; Barish, B.; Chadha, M.; Chan, S.; Cowen, D.F.; Eigen, G.; Miller, J.S.; O`Grady, C.; Urheim, J.; Weinstein, A.J.; Athanas, M.; Brower, W.; Masek, G.; Paar, H.P.; Gronberg, J.; Korte, C.M.; Kutschke, R.; Menary, S.; Morrison, R.J.; Nakanishi, S.; Nelson, H.N.; Nelson, T.K.; Qiao, C.; Richman, J.D.; Ryd, A.; Sperka, D.; Tajima, H.; Witherell, M.S.; Balest, R.; Cho, K.; Ford, W.T.; Johnson, D.R.; Lingel, K.; Lohner, M.; Rankin, P.; Smith, J.G.; Alexander, J.P.; Bebek, C.; Berkelman, K.; Bloom, K.; Browder, T.E.; Cassel, D.G.; Cho, H.A.; Coffman, D.M.; Crowcroft, D.S.; Drell, P.S.; Dumas, D.J.; Ehrlich, R.; Gaidarev, P.; Garcia-Sciveres, M.; Geiser, B.; Gittelman, B.; Gray, S.W.; Hartill, D.L.; Heltsley, B.K.; Henderson, S.; Jones, C.D.; Jones, S.L.; Kandaswamy, J.; Katayama, N.; Kim, P.C.; Kreinick, D.L.; Ludwig, G.S.; Masui, J.; Mevissen, J.; Mistry, N.B.; Ng, C.R.; Nordberg, E.; Patterson, J.R.; Peterson, D.; Riley, D.; Salman, S.; Sapper, M.; Wuerthwein, F.; Avery, P.; Freyberger, A.; Rodriguez, J.; (CLEO Co...

    1995-04-10

    We have measured the inclusive {ital b}{r_arrow}{ital s}{gamma} branching ratio to be (2.32{plus_minus}0.57{plus_minus}0.35){times}10{sup {minus}4}, where the first error is statistical and the second is systematic. Upper and lower limits on the branching ratio, each at 95% C.L., are {ital B}({ital b}{r_arrow}{ital s}{gamma}){lt}4.2{times}10{sup {minus}4} and {ital B}({ital b}{r_arrow}{ital s}{gamma}){gt}1.0{times}10{sup {minus}4}. These limits restrict the parameters of extensions of the standard model.

  7. Directional crystallization of B4C-NbB2 and B4C-MoB2 eutectic compositions

    International Nuclear Information System (INIS)

    Paderno, Varvara; Paderno, Y.B.; Filippov, Vladimir; Liashchenko, Alfred

    2004-01-01

    We studied the directional crystallization of different compositions in B 4 C-NbB 2 and B 4 C-MoB 2 systems. The eutectic compositions for both systems are evaluated. It is shown that in the first system the rod-like eutectic structure is formed, in second, the 'Chinese hieroglyphics'. In both cases high hardness and high microplasticity are observed, which are much more than for individual component phases. These compositions may be considered as a new kind of self-strengthening composite materials

  8. Urinary leukotriene E4 and 11-dehydro-thromboxane B2 excretion in children with bronchial asthma

    Directory of Open Access Journals (Sweden)

    Kaori Yoshikawa

    2004-01-01

    Conclusions: The present findings suggest that high levels of CysLTs and TXA2 are associated with the pathogenesis of bronchial asthma. The measurement of urinary LTE4 and 11DTXB2 would be useful in understanding the individual pathogenesis of asthmatic children.

  9. Polarized Structure Function $\\sigma_{LT'}$ for $p({\\vec e},e'K^+)\\Lambda$ in the Nucleon Resonance Region

    Energy Technology Data Exchange (ETDEWEB)

    Nasseripour, Rakhsha; Raue, Brian; Ambrozewicz, Pawel; Carman, Daniel; Amaryan, Moscov; Amaryan, Moskov; Anciant, Eric; Anghinolfi, Marco; Asavapibhop, Burin; Asryan, Gegham; Audit, Gerard; Auger, Thierry; Avagyan, Harutyun; Baghdasaryan, Hovhannes; Baillie, Nathan; Ball, J.P.; Ball, Jacques; Ball, J.P.; Ball, Jacques; Ball, J.P.; Ball, Jacques; Ball, J.P.; Ball, Jacques; Baltzell, Nathan; Barrow, Steve; Battaglieri, Marco; Beard, Kevin; Bedlinskiy, Ivan; Bektasoglu, Mehmet; Bellis, Matthew; Benmouna, Nawal; Berman, Barry; Biselli, Angela; Blaszczyk, Lukasz; Bonner, Billy; Bouchigny, Sylvain; Boyarinov, Sergey; Bradford, Robert; Branford, Derek; Briscoe, William; Brooks, William; Burkert, Volker; Butuceanu, Cornel; Calarco, John; Careccia, Sharon; Casey, Liam; Cetina, Catalina; Chen, Shifeng; Cheng, Lu; Cole, Philip; Collins, Patrick; Coltharp, Philip; Cords, Dieter; Corvisiero, Pietro; Crabb, Donald; Crede, Volker; Dale, Daniel; Dashyan, Natalya; De Masi, Rita; De Vita, Raffaella; De Sanctis, Enzo; Degtiarenko, Pavel; Dennis, Lawrence; Deur, Alexandre; Dhuga, Kalvir; Dickson, Richard; Djalali, Chaden; Dodge, Gail; Doughty, David; Dragovitsch, Peter; Dugger, Michael; Dytman, Steven; Dzyubak, Oleksandr; Egiyan, Hovanes; Egiyan, Kim; Elfassi, Lamiaa; Elouadrhiri, Latifa; Eugenio, Paul; Fatemi, Renee; Fedotov, Gleb; Feldman, Gerald; Feuerbach, Robert; Forest, Tony; Fradi, Ahmed; Funsten, Herbert; Garcon, Michel; Gavalian, Gagik; Gevorgyan, Nerses; Gilfoyle, Gerard; Giovanetti, Kevin; Girard, Pascal; Girod, Francois-Xavier; Goetz, John; Gothe, Ralf; Gothe, Ralf; Griffioen, Keith; Guidal, Michel; Guillo, Matthieu; Guler, Nevzat; Guo, Lei; Gyurjyan, Vardan; Hafidi, Kawtar; Hakobyan, Hayk; Hanretty, Charles; Hardie, John; Heddle, David; Hersman, F.; Hicks, Kenneth; Hleiqawi, Ishaq; Holtrop, Maurik; Hu, Jicun; Hyde, Charles; Ilieva, Yordanka; Ireland, David; Ishkhanov, Boris; Isupov, Evgeny; Ito, Mark; Jenkins, David; Jo, Hyon-Suk; Johnstone, John; Joo, Kyungseon; Juengst, Henry; Kalantarians, Narbe; Kellie, James; Khandaker, Mahbubul; Kim, Kui; Kim, Kyungmo; Kim, Wooyoung; Klein, Andreas; Klein, Franz; Kossov, Mikhail; Krahn, Zebulun; Kramer, Laird; Kubarovsky, Valery; Kuhn, Joachim; Kuhn, Sebastian; Kuleshov, Sergey; Kuznetsov, Viacheslav; Lachniet, Jeff; Laget, Jean; Langheinrich, Jorn; Lawrence, David; Livingston, Kenneth; Lu, Haiyun; Lukashin, Konstantin; MacCormick, Marion; Manak, Joseph; Markov, Nikolai; Mattione, Paul; McAleer, Simeon; McKinnon, Bryan; McNabb, John; Mecking, Bernhard; Mestayer, Mac; Meyer, Curtis; Mibe, Tsutomu; Mikhaylov, Konstantin; Minehart, Ralph; Mirazita, Marco; Miskimen, Rory; Mokeev, Viktor; Moreno, Brahim; Moriya, Kei; Morrow, Steven; Moteabbed, Maryam; Mueller, James; Munevar Espitia, Edwin; Mutchler, Gordon; Nadel-Turonski, Pawel; Niccolai, Silvia; Niculescu, Gabriel; Niculescu, Maria-Ioana; Niczyporuk, Bogdan; Niroula, Megh; Niyazov, Rustam; Nozar, Mina; Osipenko, Mikhail; Ostrovidov, Alexander; Park, Kijun; Pasyuk, Evgueni; Paterson, Craig; Pereira, Sergio; Peterson, Gerald; Philips, Sasha; Pierce, Joshua; Pivnyuk, Nikolay; Pocanic, Dinko; Pogorelko, Oleg; Pozdnyakov, Sergey; Preedom, Barry; Price, John; Procureur, Sebastien; Prok, Yelena; Protopopescu, Dan; Qin, Liming; Riccardi, Gregory; Ricco, Giovanni; Ripani, Marco; Ritchie, Barry; Rosner, Guenther; Rossi, Patrizia; Rubin, Philip; Sabatie, Franck; Salamanca, Julian; Salgado, Carlos; Santoro, Joseph; Sapunenko, Vladimir; Sayre, Donald; Schumacher, Reinhard; Serov, Vladimir; Shafi, Aziz; Sharabian, Youri; Sharov, Dmitri; Shvedunov, Nikolay; Simionatto, Sebastio; Skabelin, Alexander; Smith, Elton; Smith, Lee; Sober, Daniel; Sokhan, Daria; Stavinsky, Aleksey; Stepanyan, Samuel; Stepanyan, Stepan; Stokes, Burnham; Stoler, Paul; Strakovski, Igor; Strauch, Steffen; Taiuti, Mauro; Taylor, Shawn; Tedeschi, David; Thoma, Ulrike; Thompson, Richard; Tkabladze, Avtandil; Tkachenko, Svyatoslav; Ungaro, Maurizio; Vineyard, Michael; Vlassov, Alexander; Wang,

    2008-06-01

    The first measurements of the polarized structure function $\\sigma_{LT'}$ for the reaction $p(\\vec e,e'K^+)\\Lambda$ in the nucleon resonance region are reported. Measurements are included from threshold up to $W$=2.05 GeV for central values of $Q^2$ of 0.65 and 1.00 GeV$^2$, and nearly the entire kaon center-of-mass angular range. $\\sigma_{LT'}$ is the imaginary part of the longitudinal-transverse response and is expected to be sensitive to interferences between competing intermediate s-channel resonances, as well as resonant and non-resonant processes. The results for $\\sigma_{LT'}$ are comparable in magnitude to previously reported results from CLAS for $\\sigma_{LT}$, the real part of the same response. An intriguing sign change in $\\sigma_{LT'}$ is observed in the high $Q^2$ data at $W\\approx 1.9$ GeV. Comparisons to several existing model predictions are shown.

  10. Novel UEP LT Coding Scheme with Feedback Based on Different Degree Distributions

    Directory of Open Access Journals (Sweden)

    Li Ya-Fang

    2016-01-01

    Full Text Available Traditional unequal error protection (UEP schemes have some limitations and problems, such as the poor UEP performance of high priority data and the seriously sacrifice of low priority data in decoding property. Based on the reasonable applications of different degree distributions in LT codes, this paper puts forward a novel UEP LT coding scheme with a simple feedback to compile these data packets separately. Simulation results show that the proposed scheme can effectively protect high priority data, and improve the transmission efficiency of low priority data from 2.9% to 22.3%. Furthermore, it is fairly suitable to apply this novel scheme to multicast and broadcast environments since only a simple feedback introduced.

  11. Nanoscale characterization and local piezoelectric properties of lead-free KNN-LT-LS thin films

    Energy Technology Data Exchange (ETDEWEB)

    Abazari, M; Safari, A [Glenn Howatt Electroceramics Laboratories, Department of Materials Science and Engineering, Rutgers-The state University of New Jersey, Piscataway, NJ 08854 (United States); Choi, T; Cheong, S-W [Rutgers Center for Emergent Materials, Department of Physics and Astronomy, Rutgers-The state University of New Jersey, Piscataway, NJ 08854 (United States)

    2010-01-20

    We report the observation of domain structure and piezoelectric properties of pure and Mn-doped (K{sub 0.44},Na{sub 0.52},Li{sub 0.04})(Nb{sub 0.84},Ta{sub 0.1},Sb{sub 0.06})O{sub 3} (KNN-LT-LS) thin films on SrTiO{sub 3} substrates. It is revealed that, using piezoresponse force microscopy, ferroelectric domain structure in such 500 nm thin films comprised of primarily 180{sup 0} domains. This was in accordance with the tetragonal structure of the films, confirmed by relative permittivity measurements and x-ray diffraction patterns. Effective piezoelectric coefficient (d{sub 33}) of the films were calculated using piezoelectric displacement curves and shown to be {approx}53 pm V{sup -1} for pure KNN-LT-LS thin films. This value is among the highest values reported for an epitaxial lead-free thin film and shows a great potential for KNN-LT-LS to serve as an alternative to PZT thin films in future applications.

  12. Nanoscale characterization and local piezoelectric properties of lead-free KNN-LT-LS thin films

    Science.gov (United States)

    Abazari, M.; Choi, T.; Cheong, S.-W.; Safari, A.

    2010-01-01

    We report the observation of domain structure and piezoelectric properties of pure and Mn-doped (K0.44,Na0.52,Li0.04)(Nb0.84,Ta0.1,Sb0.06)O3 (KNN-LT-LS) thin films on SrTiO3 substrates. It is revealed that, using piezoresponse force microscopy, ferroelectric domain structure in such 500 nm thin films comprised of primarily 180° domains. This was in accordance with the tetragonal structure of the films, confirmed by relative permittivity measurements and x-ray diffraction patterns. Effective piezoelectric coefficient (d33) of the films were calculated using piezoelectric displacement curves and shown to be ~53 pm V-1 for pure KNN-LT-LS thin films. This value is among the highest values reported for an epitaxial lead-free thin film and shows a great potential for KNN-LT-LS to serve as an alternative to PZT thin films in future applications.

  13. Spontaneous regression of primary diffuse large B-cell lymphoma, leg type.

    Science.gov (United States)

    Alcántara-González, J; González-García, C; Fernández-Guarino, M; Jaén-Olasolo, P

    2014-01-01

    Primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL LT) accounts for approximately 20% of all primary cutaneous B-cell lymphomas and tends to present as infiltrated nodules, tumors, and plaques on the legs in the elderly. Unlike other primary cutaneous large B-cell lymphomas, it has a poor prognosis and tends to require treatment with systemic chemotherapy. We present the case of an 82-year-old patient with a 1-year history of nodules and plaques on her right leg. Biopsy led to a diagnosis of PCLBCL LT and the lesions resolved without treatment within 1 month of the first visit. This is an atypical course of PCLBCL LT and we believe that it is the first such case to be reported in the literature. Copyright © 2012 Elsevier España, S.L. and AEDV. All rights reserved.

  14. Effect of leukotriene receptor antagonists on vascular permeability during endotoxic shock

    International Nuclear Information System (INIS)

    Cook, J.A.; Li, E.J.; Spicer, K.M.; Wise, W.C.; Halushka, P.V.

    1990-01-01

    Evidence has accumulated that sulfidopeptide leukotrienes are significant pathogenic mediators of certain hematologic and hemodynamic sequelae of endotoxic shock. In the present study, the effects of a selective LTD4/E4 receptor antagonist, LY171883 (LY), or a selective LTD4 receptor antagonist, SKF-104353 (SKF), were assessed on splanchnic and pulmonary localization of 99mTechnetium-labeled human serum albumin (99mTc-HSA) in acute endotoxic shock in the rat. Dynamic gamma camera imaging of heart (H), midabdominal (GI), and lung regions of interest generated time activity curves for baseline and at 5-35 min after Salmonella enteritidis endotoxin (10 mg/kg, i.v.). Slopes of GI/H and lung/H activity (permeability index, GI/H or lung/H X 10(-3)/min) provided indices of intestinal and lung localization. Rats received LY (30 mg/kg, i.v.), LY vehicle (LY Veh), SKF (10 mg/kg), or SKF vehicle (SK Veh) 10 min prior to endotoxin or endotoxin vehicle. In rats receiving the LY Veh and endotoxin (n = 8) or SKF Veh and endotoxin (n = 12), the splanchnic permeability indices to 99mTc-HSA were increased 11.2-fold and 5.1-fold, respectively (P less than 0.05) compared to vehicle control groups not given endotoxin (n = 5). Pulmonary permeability index for 99mTc-HSA was increased (P less than 0.05) to a lesser extent (3.2-fold) by endotoxin compared to vehicle controls. Pretreatment with SKF reduced the mesenteric permeability index to control levels (P less than 0.05) during the 5-35 min time interval post-endotoxin. LY reduced the mesenteric permeability index by 70%. Pulmonary relative permeability to 99mTc-HSA was not affected by LY pretreatment. Both splanchnic and lung relative permeability to the isotope was transient; at 135-225 min post-endotoxin, splanchnic localization of 99mTc-HSA (n = 4) was not significantly different from vehicle controls in these vascular beds

  15. Murine and human b locus pigmentation genes encode a glycoprotein (gp75) with catalase activity

    International Nuclear Information System (INIS)

    Halaban, R.; Moellmann, G.

    1990-01-01

    Melanogenesis is regulated in large part by tyrosinase, and defective tyrosinase leads to albinism. The mechanisms for other pigmentation determinants (e.g., those operative in tyrosinase-positive albinism and in murine coat-color mutants) are not yet known. One murine pigmentation gene, the brown (b) locus, when mutated leads to a brown (b/b) or hypopigmentated (B lt /B lt ) coat versus the wild-type black (B/B). The authors show that the b locus codes for a glycoprotein with the activity of a catalase (catalase B). Only the c locus protein is a tyrosinase. Because peroxides may be by-products of melanogenic activity and hydrogen peroxide in particular is known to destroy melanin precursors and melanin, they conclude that pigmentation is controlled not only by tyrosinase but also by a hydroperoxidase. The studies indicate that catalase B is identical with gp75, a known human melanosomal glycoprotein; that the b mutation is in a heme-associated domain; and that the B lt mutation renders the protein susceptible to rapid proteolytic degradation

  16. The effect of rider weight and additional weight in Icelandic horses in tölt: part II. Stride parameters responses.

    Science.gov (United States)

    Gunnarsson, V; Stefánsdóttir, G J; Jansson, A; Roepstorff, L

    2017-09-01

    This study investigated the effects of rider weight in the BW ratio (BWR) range common for Icelandic horses (20% to 35%), on stride parameters in tölt in Icelandic horses. The kinematics of eight experienced Icelandic school horses were measured during an incremental exercise test using a high-speed camera (300 frames/s). Each horse performed five phases (642 m each) in tölt at a BWR between rider (including saddle) and horse starting at 20% (BWR20) and increasing to 25% (BWR25), 30% (BWR30), 35% (BWR35) and finally 20% (BWR20b) was repeated. One professional rider rode all horses and weight (lead) was added to saddle and rider as needed. For each phase, eight strides at speed of 5.5 m/s were analyzed for stride duration, stride frequency, stride length, duty factor (DF), lateral advanced placement, lateral advanced liftoff, unipedal support (UPS), bipedal support (BPS) and height of front leg action. Stride length became shorter (Y=2.73-0.004x; P0.05). In conclusion, increased BWR decreased stride length and increased DF proportionally to the same extent in all limbs, whereas BPS increased at the expense of decreased UPS. These changes can be expected to decrease tölt quality when subjectively evaluated according to the breeding goals for the Icelandic horse. However, beat, symmetry and height of front leg lifting were not affected by BWR.

  17. Pilot study of whole-blood gamma interferon response to the Vibrio cholerae toxin B subunit and resistance to enterotoxigenic Escherichia coli-associated diarrhea.

    Science.gov (United States)

    Flores, Jose; DuPont, Herbert L; Paredes-Paredes, Mercedes; Aguirre-Garcia, M Magdalena; Rojas, Araceli; Gonzalez, Alexei; Okhuysen, Pablo C

    2010-05-01

    Enterotoxigenic Escherichia coli (ETEC), which produces heat-labile toxin (LT), is a common cause of travelers' diarrhea (TD). The B subunit of ETEC LT is immunologically related to the B subunit of Vibrio cholerae toxin (CT). In this pilot study we evaluated the whole-blood gamma interferon response to CT B in 17 U.S. adults traveling to Mexico. Only one of nine subjects who demonstrated a cellular immune response as determined by whole-blood gamma interferon production to CT B on arrival to Mexico developed diarrhea, whereas five of eight without a cellular response developed diarrhea. Markers of the cellular immune response to ETEC LT could help in identifying individuals immune to ETEC LT, and these markers deserve additional study.

  18. Starter Kültür Kullanılarak Yapılan Tulum Peynirlerinin Bazı Özellikleri

    Directory of Open Access Journals (Sweden)

    Zübeyde Öner

    2015-02-01

    Full Text Available Bu çalışmada, tulum peyniri kalitesi üzerinde starter kültür kullanımının etkileri ve tulum peyniri üretimine uygun starter kültür karışımı araştırılmıştır. Bu amaçla çiğ sütten ve starter kültür olarak Lactobacillus plantarum 1, Lb. plantarum 48, Lactococcus lactis 57, Enterococcus faecalis 40’ın farklı oranlardaki karışımları kullanılarak 3 farklı peynir üretilmiştir. 90 günlük olgunlaşma sonunda toplam kurumadde %57,85-61,09, SH 79,5-94 olgunlaşma katsayısı 51,48-136,32, kurumaddede tuz %4,03-5,26 kurumaddede yağ %54,42-57,29, toplam azot % 2,67-3,43 suda çözünen azot % 1,73-3,64 duyusal değerlendirme sonucu 52-72,81 toplam puan arasında değişmiştir. Mikrobiyolojik analiz sonuçlarına göre 90 günlük olgunlaşma sonunda toplam mezofil aerob bakteri sayısı 7,25-7,97 log kob/g, laktobasil 7,32-7,5 log kob/g, laktokok 7,71-8,15 log kob/g, koliform 1,73-5,02 log kob/g, S. aureus <10-2,35 log kob/g, enterokok 6,71-7,38 log kob/g, psikrofilik mikroorganizma <10 log kob/g, maya ve küf 4,22-5,49 log kob/g arasında değişmiştir.

  19. Anti-inflammatory activity of 6-hydroxy-2,7-dimethoxy-1,4-henanthraquinone from tuberous roots of yam (Dioscorea batatas) through inhibition of prostaglandin D₂ and leukotriene C₄ production in mouse bone marrow-derived mast cells.

    Science.gov (United States)

    Jin, Meihua; Lu, Yue; Yang, Ju Hye; Jo, Tae Hyung; Park, Young In; Lee, Chong-Kil; Park, Sang-Jo; Son, Kun Ho; Chang, Hyeun Wook

    2011-09-01

    6-Hydroxy-2,7-dimethoxy-1,4-phenanthraquinone (PAQ) isolated from the tuberous roots of Yam (Dioscorea batatas) inhibited cyclooxygenase-2 (COX-2) and cyclooxygenase-1 (COX-1) dependent prostaglandin D(2) (PGD(2)) generation in mouse bone marrow-derived mast cells in a concentration-dependent manner with IC(50) values of 0.08 μM and 0.27 μM, respectively. In the Western blotting with specific anti-COX-2 antibodies, the decrease of the quantity of PGD(2) was accompanied by a decrease in the COX-2 protein level. But PAQ did not affect COX-1 protein level. In addition, this compound inhibited 5-lipoxygenase (5-LOX) dependent production of leukotriene C(4) in a dose-dependent manner, with an IC(50) of 0.032 μM. These results demonstrate that PAQ has a dual COX-2/5-LOX inhibitory activity. This compound also inhibited the degranulation reaction in a dose-dependent manner with an IC(50) of 2.7 μM. Thus, these results suggest that PAQ may be useful in regulating mast cell-mediated inflammatory diseases.

  20. AutoCAD / AutoCAD LT 2014 fundamentals metric

    CERN Document Server

    ASCENT center for technical knowledge

    2014-01-01

    The objective of AutoCAD/AutoCAD LT 2014 Fundamentals is to enable students to create a basic 2D drawing in the AutoCAD software. Even at this fundamental level, the AutoCAD software is one of the most sophisticated computer applications that you are likely to encounter. Therefore learning to use it can be challenging. To make the process easier and provide flexibility for instructors and students, the training guide is divided into two parts that can be taken independently.

  1. LT-CFB. Further development and commercialization. Final report. [Low Temperature Circulating Fluid Bed gasifier]; LT-CFB. Videreudvikling og kommercialisering. Slutrapport

    Energy Technology Data Exchange (ETDEWEB)

    Stoholm, P. [DFBT, Roskilde (Denmark); Birk Henriksen, U.; Ahrentfeldt, J. [Technical Univ. of Denmark. DTU Chemical Engineering, CHEC Research Centre, Roskilde (Denmark); Cramer, J.; Dietrich, J.; Christiansen, Knud [FORCE Technology, Kgs. Lyngby (Denmark); Krogh, J. [Anhydro A/S, Soeborg (Denmark)

    2011-12-15

    The starting point for the project was the good results achieved in a previous project, in which a series of experiments were carried out with a 500 kW pilot plant at teh Technical University of Denmark. The main task was then to find a way forward towards further scale-up, demonstration and commercialization. The project's partners chose to study three possible sites for demonstration. However, during the project both framework conditions as well as DONG Energy's strategy changed, which resulted in the company taking over the LT-CFB technology in December 2009. As a first step a 6 MW demonstration plant will now be set up at the Asnaes power plant expected to start in spring 2011. The project has also been buit a new mobile 100 kW LT-CFB plant for the further optimization of the process and for short-term trials of new fuels. At the new plant a number of successful trials were performed with straw and residual fibers. Furthermore, it is experimentally demonstrated that it is possible to cool the tar-containing gas to approx. 300 degrees C and purify the gas in a bag filter, so it can be used in natural gas-fired power plant boilers. With the new mobile system, it will now be easier to perform experiments with a number of new fuels such as unsorted municipal waste, bone meal and dried sewage sludge. (LN)

  2. The effect of triiodothyronine (L-T3) and weight loss on sex-hormone binding globulin (SHBG) in hirsute obese women

    International Nuclear Information System (INIS)

    Cavaliere, H.; Medeiros Neto, G.A.

    1984-01-01

    The effect of a 60-day period of treatment with L-T 3 (200 μg/day) was evaluated in hirsute obese women and normal controls. The obese patients were also submitted to a low calorie high protein. Mean initial weight significantly declined with a significant lowering of the mean DHEA-S leves. There was changes in serum T 3 rose in both obese and normal patients. Serum sex-hormone binding globulin levels at baseline studies were significantly higher in normal controls than in obese patients. At the end of de 60-day period of L-T 3 administration it was observed in both groups a 2-4 fold increase in serum SHBG levels but normal controls had significantly higher mean values than obese individuals. (M.A.C.) [pt

  3. Association of donor and recipient SUMO4 rs237025 genetic variant with new-onset diabetes mellitus after liver transplantation in a Chinese population.

    Science.gov (United States)

    Zhang, Tao; Liu, Yuan; Hu, Yibo; Zhang, Xiaoqing; Zhong, Lin; Fan, Junwei; Peng, Zhihai

    2017-09-05

    New-onset diabetes mellitus (NODM) is a common complication after liver transplantation (LT). The small ubiquitin-like modifier 4 (SUMO4) rs237025 polymorphism has been reported to be associated with type 2 diabetes mellitus (T2DM). In this study, we aimed to evaluate the association of donor and recipient SUMO4 rs237025 polymorphisms with NODM and the long-term consequences of NODM after LT. A total of 126 liver transplant patients were enrolled in the study. One single nucleotide polymorphism, SUMO4 rs237025, was genotyped in both donors and recipients. Both donor and recipient SUMO4 rs237025 polymorphisms were found to be significantly associated with NODM after LT. In multivariate analysis, recipient age>50 years, tacrolimus trough concentrations>10ng/mL at 1month after LT, donor and recipient rs237025 genetic variant, and the combined donor and recipient rs237025 genetic variant were independent predictive factors of NODM. Area under the receiver operating characteristic curve (AUROC) analysis indicated the higher predictive ability of the model containing combined donor and recipient rs237025 polymorphisms than the clinical model (p=0.046). Furthermore, Kaplan-Meier survival analysis demonstrated that NODM was related to significantly poorer patient survival in comparison with non-NODM patients (p=0.041). Both donor and recipient SUMO4 rs237025 polymorphisms contribute to the development of NODM after LT and NODM is a frequent complication that negatively affects patient survival. Copyright © 2017. Published by Elsevier B.V.

  4. Mardin Süryanilerinde Belleğin Teolojik-Kültürel Çerçevesi / Theological - Cultural Framework of Memory in Mardin Syriacs

    Directory of Open Access Journals (Sweden)

    Tahir Pekasil

    2016-05-01

    Full Text Available Theological - Cultural Framework of Memory in Mardin Syriacs Abstract In this article, “theological/ritual-cultural framework of memory”, "memory participation tools" "recall figures" will be examined in the case of Mardin Syriac Orthodox Church. "Ritual participation" and "rhythmic repetition" which enables "theological-social inclusion" and "integration", also mobilizes remembering instruments and guarantees protection, revival and transfer of cultural memory. This also ensures continuation of sense of belonging. Priests who are accepted as "vicarious memory" enable participation to memory in church which is a "memory space" mediating to the "transmission of blessing and grace by ritual representation". Priests also by institutionalizing ceremonies and rituals which integrated with music, makes cultural meanings functional. The theme is discussed from the perspective of cultural memory and supported by face to face interviews. Mardin Süryanilerinde Belleğin Teolojik-Kültürel Çerçevesi Öz Bu yazıda, Mardin Süryani Ortodoks Kilisesi örneğinden hareketle “belleğin teolojik/ritüel- kültürel çerçevesi”, “belleğe katılım araçları”, “hatırlama figürleri” ele alınacaktır. “Teolojik ve toplumsal katılımı”, “bütünleşmeyi” sağlayan “ritüel katılım” ve “ritmik tekrar”, hatırlama araçlarını harekete geçirerek kültürel belleğin korunmasını, canlandırılmasını ve aktarılmasını garanti etmekte, aidiyetin devamını sağlamaktadır. Belleğe katılımı sağlayan “vekil hafıza” olarak kabul edilen papazlar, bir “hafıza mekânı” olan kilisede, “inayetin ritüel temsille aktarımına” aracılık yapmakta; “ritüel tasarım” yoluyla müzikle bütünleştirdikleri ayin ve ritüelleri kurumsallaştırarak kültürel anlamlara işlerlik kazandırmaktadırlar. Çalışma konusu, kültürel bellek perspektifinden ele alınmış ve mülakat örnekleri ile desteklenmiştir.

  5. Comparison of “Morning Olifera Seed Extract and Magnafloc LT25” in Removal of Water Turbidity Case Study: Tehran’s Jalalieh (1 Water Treatment Plant

    Directory of Open Access Journals (Sweden)

    Mehdi Khan ahmadi

    2013-08-01

    Full Text Available Coagulation-flocculation is one of the most important processes for water treatment, commonly used all over the world. The use of synthetic polymers known as “Polyelectrolytes as a coagulant aid is now wide spread in water treatment plants. Tehran’s “Jalalieh WTP” has been using an anionic polyelectrolyte under the trade name of “Magna Floc LT25” for a number of years MagnaFloc LT25 (MF-LT25 is a synthetic coagulant with high molecular weight, produced in granular and powder form. The application of this coagulant aid is known to be most effective if injected to water after addition of main coagulant (Ferric Chloride in Tehran’s WTP.  However the use of synthetic polymers in treatment of drinking water has always been under question due to extract of MO seed contains proteins soluble in water which have high coagulating properties. This pilot scale study was performed to compare the coagulating properties of seed extract of MO to MF-LT25, The tests were carried out on Tehran’s raw water in Jalalieh treatment plant. Several turbidity ranges such as 5, 20, 100, and 200 NTU were used representing real seasonal turbidities of influent water to treatment plant. Optimum concentration of the coagulant and coagulant aid was determined within water pH values of 6, 7 and 8, using common “Jar Test” technique. The extract of Moringa Oleifera seed in optimum concentration of 10, 14,25,35 mg/L and optimum pH of 8 is capable in removal of 96.5, 97.4, 98.5 and 99% of water turbidity range of 5, 20, 100, and 200 NTU respectively. Under similar conditions, MF-LT25 removal efficiency were found 97, 98.1, 98.4 and 99.4% of water turbidity range of 5, 20, 100, and 200 NTU at optimum concentrations of 0.015, 0.02, 0.025, 0.03 mg/L respectively. The results also showed that the extract of Moringa Oleifera seed is a powerful coagulating agent, at alkalinity pH values, and is more effective for high turbid waters. It compared well with synthetic

  6. Qatar Exoplanet Survey : Qatar-3b, Qatar-4b, and Qatar-5b

    Science.gov (United States)

    Alsubai, Khalid; Mislis, Dimitris; Tsvetanov, Zlatan I.; Latham, David W.; Bieryla, Allyson; Buchhave, Lars A.; Esquerdo, Gilbert A.; Bramich, D. M.; Pyrzas, Stylianos; Vilchez, Nicolas P. E.; Mancini, Luigi; Southworth, John; Evans, Daniel F.; Henning, Thomas; Ciceri, Simona

    2017-04-01

    We report the discovery of Qatar-3b, Qatar-4b, and Qatar-5b, three new transiting planets identified by the Qatar Exoplanet Survey. The three planets belong to the hot Jupiter family, with orbital periods of {P}{{Q}3{{b}}} = 2.50792 days, {P}{{Q}4{{b}}} = 1.80539 days, and {P}{{Q}5{{b}}} = 2.87923 days. Follow-up spectroscopic observations reveal the masses of the planets to be {M}{{Q}3{{b}}} = 4.31 ± 0.47 {M}{{J}}, {M}{{Q}4{{b}}} = 6.10 ± 0.54 {M}{{J}}, and {M}{{Q}5{{b}}} = 4.32 ± 0.18 {M}{{J}}, while model fits to the transit light curves yield radii of {R}{{Q}3{{b}}} = 1.096 ± 0.14 {R}{{J}}, {R}{{Q}4{{b}}} = 1.135 ± 0.11 {R}{{J}}, and {R}{{Q}5{{b}}} = 1.107 ± 0.064 {R}{{J}}. The host stars are low-mass main sequence stars with masses and radii M Q3 = 1.145 ± 0.064 M ⊙, M Q4 = 0.896 ± 0.048 M ⊙, M Q5 = 1.128 ± 0.056 M ⊙ and R Q3 = 1.272 ± 0.14 R ⊙, R Q4 = 0.849 ± 0.063 R ⊙, and R Q5 = 1.076 ± 0.051 R ⊙ for Qatar-3, 4, and 5 respectively. The V magnitudes of the three host stars are V Q3 = 12.88, V Q4 = 13.60, and V Q5 = 12.82. All three new planets can be classified as heavy hot Jupiters (M > 4 M J).

  7. 75 FR 27956 - Airworthiness Directives; Airbus Model A300 B4-600, B4-600R, and F4-600R Series Airplanes, and...

    Science.gov (United States)

    2010-05-19

    ... B4-600, B4-600R, and F4-600R Series Airplanes, and Model C4-605R Variant F Airplanes (Collectively...-203, and B4-203 airplanes; Model A300 B4-601, B4- 603, B4-620, B4-622, B4-605R, B4-622R, F4-605R, F4...

  8. Clinical experience with EDAP LT-01+ extracorporeal shock wave lithotripsy for radiolucent stones; a report of 27 cases

    International Nuclear Information System (INIS)

    Rim, Hee Kwan; Kim, Ho Sung; Rim, Joung Sik

    1994-01-01

    Between February 1990 and February 1993, Radiolucent stones of 27 renal units in 22 patients were treated by extracorporeal shock wave lithotripsy (ESWL) using the EDAP LT-01+. Intravenous urography was done in all patients for the diagnosis of radiolucent stones. Retrograde pyelography, ultrasonography and/or computed tomography was done, if needed. The locations of stones were kidney in 11(40.7 %), upper ureter in 8(29.6 %), lower ureter in 6(22.2 %), bladder in 1(3.7 %), ureteropelvic junction in 1(3.7 %). The average stone size was 10.9mm with a range of 5 to 32mm in maximum diameter. The average numbers of treatment were 2.7 sessions and average storage required was 34.8 in one session. The average treatment time was 40.4 minutes. All the patients showed complete removal of all calculous materials. Of 17 urinary stones analysed by chemical method, 8(47.1 %) were composed of uric acid, 5(29.4 %) of uric acid and calcium, 3 of phosphate and 1 of carbonate and phosphate. Therefore, we conclude that ESWL with EDAP LT-01+ lithotriptor is considered to be an effective noninvasive procedure for treatment of radiolucent stones. (Author)

  9. 75 FR 60611 - Airworthiness Directives; Airbus Model A300 B4-600, B4-600R, and F4-600R Series Airplanes, and...

    Science.gov (United States)

    2010-10-01

    ... Airworthiness Directives; Airbus Model A300 B4-600, B4-600R, and F4-600R Series Airplanes, and Model A300 C4...; Model A300 B4-601, B4- 603, B4-620, B4-622, B4-605R, B4-622R, F4-605R, F4-622R, and C4-605R Variant F...-- Dated-- A300 series airplanes......... A300-32A0447..... April 22, 2004. A300 B4-600, B4-600R, and F4...

  10. 76 FR 27242 - Airworthiness Directives; Airbus Model A300 B4-600, B4-600R, and F4-600R Series Airplanes, and...

    Science.gov (United States)

    2011-05-11

    ... Airworthiness Directives; Airbus Model A300 B4-600, B4-600R, and F4-600R Series Airplanes, and Model C4-605R... applies to all Airbus Model A300 B4-601, B4-603, B4- 620, B4-622, B4-605R, B4-622R, F4-605R, F4-622R, and...

  11. 76 FR 59008 - Airworthiness Directives; Airbus Model A300 B4-600, B4-600R, and F4-600R Series Airplanes, and...

    Science.gov (United States)

    2011-09-23

    ... Airworthiness Directives; Airbus Model A300 B4-600, B4-600R, and F4-600R Series Airplanes, and Model C4-605R... to Airbus Model A300 B4-601, B4-603, B4-620, B4-622, B4-605R, B4-622R, F4-605R, F4-622R, and C4-605R...

  12. Ordered perovskites with cationic vacancies. 9. Compounds of the type Sr/sub 2/Srsub(1/4)Bsub(1/2)sup(III)vacantsub(1/4)WO/sub 6/ equivalent to Sr/sub 8/SrB/sub 2/sup(III)vacantW/sub 4/O/sub 24/ (Bsup(III) = La, Pr, Nd, Sm - Tm, Y)

    Energy Technology Data Exchange (ETDEWEB)

    Kemmler-Sack, S; Ehmann, A [Tuebingen Univ. (Germany, F.R.). Lehrstuhl fuer Anorganische Chemie 2

    1981-08-01

    The compounds Sr/sub 2/Srsub(1/4)Bsub(1/2)sup(III)vacantsub(1/4)WO/sub 6/ equivalent to Sr/sub 8/SrB/sub 2/sup(III)vacantW/sub 4/O/sub 24/ belong to the group of perovskites with octahedral cationic vacancies (cation/vacancy ratio (CN 6) = 7:1). For the larger Bsup(III) ions (La, Pr, Nd, Sm-Dy) different ordering effects are observed. The perovskites with Bsup(III) = Sm, Eu, Gd are polymorphic too (HT modification: higher ordered cubic perovskite (Bsup(III) = Gd: a = 2 x 8.23/sub 4/ A); LT modification: hexagonal perovskite stacking polytype (Bsup(III) = Gd: a = 9.95/sub 4/ A; c = 19.0/sub 4/ A)). With the smaller Bsup(III) ions (Ho, Er, Tm and Y) a cubic, 1:1 ordered perovskite type is observed.

  13. Contempt-LT: a computer program for predicting containment pressure-temperature response to a loss-of-coolant accident

    International Nuclear Information System (INIS)

    Wheat, L.L.; Wagner, R.J.; Niederauer, G.F.; Obenchain, C.F.

    1975-06-01

    CONTEMPT-LT is a digital computer program, written in FORTRAN IV, developed to describe the long-term behavior of water-cooled nuclear reactor containment systems subjected to postulated loss-of-coolant accident (LOCA) conditions. The program calculates the time variation of compartment pressures, temperatures, mass and energy inventories, heat structure temperature distributions, and energy exchange with adjacent compartments. The program is capable of describing the effects of leakage on containment response. Models are provided to describe fan cooler and cooling spray engineered safety systems. Up to four compartments can be modeled with CONTEMPT-LT, and any compartment except the reactor system may have both a liquid pool region and an air-vapor atmosphere region above the pool. Each region is assumed to have a uniform temperature, but the temperatures of the two regions may be different. CONTEMPT-LT can be used to model all current boiling water reactor pressure suppression systems, including containments with either vertical or horizontal vent systems. CONTEMPT-LT can also be used to model pressurized water reactor dry containments, subatmospheric containments, and dual volume containments with an annulus region, and can be used to describe containment responses in experimental containment systems. The program user defines which compartments are used, specifies input mass and energy additions, defines heat structure and leakage systems, and describes the time advancement and output control. CONTEMPT-LT source decks are available in double precision extended-binary-coded-decimal-interchange-code (EBCDIC) versions. Sample problems have been run on the IBM360/75 computer. (U.S.)

  14. Thermophysical properties of the ionic liquids [EMIM][B(CN)4] and [HMIM][B(CN)4].

    Science.gov (United States)

    Koller, Thomas M; Rausch, Michael H; Ramos, Javier; Schulz, Peter S; Wasserscheid, Peter; Economou, Ioannis G; Fröba, Andreas P

    2013-07-18

    In the present study, the thermophysical properties of the tetracyanoborate-based ionic liquids (ILs) 1-ethyl-3-methylimidazolium tetracyanoborate ([EMIM][B(CN)4]) and 1-hexyl-3-methylimidazolium tetracyanoborate ([HMIM][B(CN)4]) obtained by both experimental methods and molecular dynamics (MD) simulations are presented. Conventional experimental techniques were applied for the determination of refractive index, density, interfacial tension, and self-diffusion coefficients for [HMIM][B(CN)4] at atmospheric pressure in the temperature range from 283.15 to 363.15 K. In addition, surface light scattering (SLS) experiments provided accurate viscosity and interfacial tension data. As no complete molecular parametrization was available for the MD simulations of [HMIM][B(CN)4], our recently developed united-atom force field for [EMIM][B(CN)4] was partially transferred to the homologous IL [HMIM][B(CN)4]. Deviations between our simulated and experimental data for the equilibrium properties are less than ±0.3% in the case of density and less than ±8% in the case of interfacial tension for both ILs. Furthermore, the calculated and measured data for the transport properties viscosity and self-diffusion coefficient are in good agreement, with deviations of less than ±30% over the whole temperature range. In addition to a comparison with the literature, the influence of varying cation chain length on thermophysical properties of [EMIM][B(CN)4] and [HMIM][B(CN)4] is discussed.

  15. Exhaled breath condensate cysteinyl leukotrienes and airway remodeling in childhood asthma: a pilot study

    Directory of Open Access Journals (Sweden)

    Kharitonov Sergei A

    2006-04-01

    Full Text Available Abstract Background It has been suggested that cysteinyl leukotrienes (cysLTs play an important role in airway remodeling. Previous reports have indicated that cysLTs augment human airway smooth muscle cell proliferation. Recently, cysLTs have been measured in exhaled breath condensate (EBC. The aim of this study was to evaluate the relationship between cysLTs in EBC and another marker of airway remodeling, reticular basement membrane (RBM thickening, in endobronchial biopsies in children. Methods 29 children, aged 4–15 years, with moderate to severe persistent asthma, who underwent bronchoscopy as part of their clinical assessment, were included. Subjects underwent spirometry and EBC collection for cysLTs analysis, followed by bronchoscopy and endobronchial biopsy within 24 hours. Results EBC cysLTs were significantly lower in asthmatic children who were treated with montelukast than in those who were not (median (interquartile range 36.62 (22.60–101.05 versus 249.1 (74.21–526.36 pg/ml, p = 0.004. There was a significant relationship between EBC cysLTs and RBM thickness in the subgroup of children who were not treated with montelukast (n = 13, r = 0.75, p = 0.003. Conclusion EBC cysLTs appear to be associated with RBM thickening in asthma.

  16. Autodesk Inventor 2012 and Inventor LT 2012 Essentials

    CERN Document Server

    Tremblay, Thom

    2011-01-01

    Essential guide to learning Autodesk Inventor and Inventor LT The new Essentials books from Sybex are beautiful, task-based, full-color Autodesk Official Training Guides that help you get up to speed on Autodesk topics quickly and easily. Inventor Essentials thoroughly covers core features and functions of Autodesk's industry-leading 3D mechanical design software, teaching you what you need to become quickly productive with the software. By following the book's clear explanations, practical tutorials, and step-by-step exercises, you'll cover all the bases. Topics include drawing, modeling part

  17. 76 FR 38069 - Airworthiness Directives; Airbus Model A300 B4-600, B4-600R, and F4-600R Series Airplanes, and...

    Science.gov (United States)

    2011-06-29

    ... B4-600, B4-600R, and F4-600R Series Airplanes, and Model C4-605R Variant F Airplanes (Collectively...-603, B4-620, B4-622, B4-605R, B4-622R, F4-605R, F4-622R, and C4-605R Variant F airplanes; and Model...

  18. The linkage between Churg-Strauss syndrome and leukotriene receptor antagonists: fact or fiction?

    Science.gov (United States)

    McDanel, Deanna L; Muller, Barbara A

    2005-01-01

    Epidemiologic evidence has shown that the worldwide prevalence of asthma is increasing. The leukotriene receptor antagonists (LTRAs) represent a new class of therapy for asthma. They have been developed in the last decade and play a pivotal steroid-sparing role in treating the inflammatory component of asthma. Consequently, reports of Churg-Strauss syndrome (CSS), a rare form of systemic vasculitis, have been recognized as a potential side effect in individuals with moderate to severe asthma on LTRA therapy. The serious nature of this disorder is worthy of prompt recognition by clinicians and aggressive therapy to avoid the subsequent longstanding effects of vasculitis. To validate the postulated linkage between the LTRAs and CSS, this review comprehensively evaluates reported cases in the literature and supports a pathophysiological relationship between the LTRAs and the development of CSS. PMID:18360552

  19. Spontaneous regression of primary cutaneous diffuse large B-cell lymphoma, leg type with significant T-cell immune response

    Directory of Open Access Journals (Sweden)

    Paul M. Graham, DO

    2018-05-01

    Full Text Available We report a case of histologically confirmed primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT that subsequently underwent spontaneous regression in the absence of systemic treatment. The case showed an atypical lymphoid infiltrate that was CD20+ and MUM-1+ and CD10–. A subsequent biopsy of the spontaneously regressed lesion showed fibrosis associated with a lymphocytic infiltrate comprising reactive T cells. PCDLBCL-LT is a cutaneous B-cell lymphoma with a poor prognosis, which is usually treated with chemotherapy. We describe a case of clinical and histologic spontaneous regression in a patient with PCDLBCL-LT who had a negative systemic workup but a recurrence over a year after his initial presentation. Key words: B cell, lymphoma, primary cutaneous diffuse large B-cell lymphoma, leg type, regression

  20. VizieR Online Data Catalog: L/T transition dwarfs search with PS1 & WISE. II. (Best+, 2015)

    Science.gov (United States)

    Best, W. M. J.; Liu, M. C.; Magnier, E. A.; Deacon, N. R.; Aller, K. M.; Redstone, J.; Burgett, W. S.; Chambers, K. C.; Draper, P.; Flewelling, H.; Hodapp, K. W.; Kaiser, N.; Metcalfe, N.; Tonry, J. L.; Wainscoat, R. J.; Waters, C.

    2016-03-01

    We used the new Pan-STARRS1 Survey (PS1; Kaiser et al. 2010SPIE.7733E..0EK) detections through 2012 January cross-matched with the Wide-field Infrared Survey Explorer (WISE; Wright et al. 2010AJ....140.1868W) All-sky Release using a 3" matching radius. In Best et al. (2013ApJ...777...84B; Paper I), we presented seven initial discoveries from our search, all bright L/T transition dwarfs within 15pc. In this paper, we present the complete results of our search, including 79 total L/T transition dwarfs and 23 young or potentially young late-M and L dwarfs. The PS1 3π survey (K. C. Chambers et al. 2016AAS...22732407C) has obtained an average of ~12 epochs of imaging in five optical bands (gP1, rP1, iP1, zP1, yP1) with a 1.8-m wide-field telescope on Haleakala, Maui, covering the entire sky north of -30° declination. Imaging began in 2010 May and concluded in 2014 March. The WISE All-sky Source Catalog (Cutri et al. 2012, II/311) comprises data taken between 2010 January and August in four mid-infrared bands: W1 (3.6um), W2 (4.5um), W3 (12um), and W4 (22um). We searched the UKIDSS Data Release 9 (DR9; Lawrence et al. 2013, II/319) and VISTA Hemisphere Survey (Cross et al. 2012A&A...548A.119C) catalogs for JHK photometry of our candidates on the Mauna Kea Observatories (MKO) filter system. For objects not found in either survey, we obtained follow-up images using WFCAM on the 3.8m United Kingdom InfraRed Telescope (UKIRT) as part of the UKIRT Service Program. Observations took place on multiple nights spanning 2010 September to 2013 December. We obtained low-resolution near-IR spectra for our 142 candidates between 2012 July and 2014 January using the NASA IRTF/SpeX spectrograph (details of our observations are listed in table 3). (7 data files).

  1. Ion heating at the disruptive instability in the LT-3 Tokamak

    International Nuclear Information System (INIS)

    Bell, M.G.; Hutchinson, I.H.

    1976-01-01

    Measurements of the ion temperature and the toroidal current density and electric field during the disruptive instability in LT-3 are presented. Rapid ion heating and strong current inhibition have been observed. Fluctuation measurements suggest that these effects may be attributable to the excitation of ion cyclotron drift waves in the plasma

  2. Short syntheses of enantiopure calystegine B-2, B-3, and B-4

    DEFF Research Database (Denmark)

    Skaanderup, Philip Robert; Madsen, Robert

    2001-01-01

    Calystegine B-2 B-3, and B-4 have been prepared in 5 steps from the benzyl protected methyl 6-iodoglycopyranosides of glucose, galactose and mannose, respectively, by using a zinc-mediated domino reaction followed by ring-closing olefin metathesis as the key steps.......Calystegine B-2 B-3, and B-4 have been prepared in 5 steps from the benzyl protected methyl 6-iodoglycopyranosides of glucose, galactose and mannose, respectively, by using a zinc-mediated domino reaction followed by ring-closing olefin metathesis as the key steps....

  3. High performance ceria-bismuth bilayer electrolyte low temperature solid oxide fuel cells (LT-SOFCs) fabricated by combining co-pressing with drop-coating

    KAUST Repository

    Hou, Jie

    2015-03-24

    The Sm0.075Nd0.075Ce0.85O2-δ-Er0.4Bi1.6O3 bilayer structure film, which showed an encouraging performance in LT-SOFCs, was successfully fabricated by a simple low cost technique combining one-step co-pressing with drop-coating.

  4. High performance ceria-bismuth bilayer electrolyte low temperature solid oxide fuel cells (LT-SOFCs) fabricated by combining co-pressing with drop-coating

    KAUST Repository

    Hou, Jie; Bi, Lei; Qian, Jing; Zhu, Zhiwen; Zhang, Junyu; Liu, Wei

    2015-01-01

    The Sm0.075Nd0.075Ce0.85O2-δ-Er0.4Bi1.6O3 bilayer structure film, which showed an encouraging performance in LT-SOFCs, was successfully fabricated by a simple low cost technique combining one-step co-pressing with drop-coating.

  5. LT^2C^2: A language of thought with Turing-computable Kolmogorov complexity

    Directory of Open Access Journals (Sweden)

    Santiago Figueira

    2013-03-01

    Full Text Available In this paper, we present a theoretical effort to connect the theory of program size to psychology by implementing a concrete language of thought with Turing-computable Kolmogorov complexity (LT^2C^2 satisfying the following requirements: 1 to be simple enough so that the complexity of any given finite binary sequence can be computed, 2 to be based on tangible operations of human reasoning (printing, repeating,. . . , 3 to be sufficiently powerful to generate all possible sequences but not too powerful as to identify regularities which would be invisible to humans. We first formalize LT^2C^2, giving its syntax and semantics, and defining an adequate notion of program size. Our setting leads to a Kolmogorov complexity function relative to LT^2C^2 which is computable in polynomial time, and it also induces a prediction algorithm in the spirit of Solomonoff’s inductive inference theory. We then prove the efficacy of this language by investigating regularities in strings produced by participants attempting to generate random strings. Participants had a profound understanding of randomness and hence avoided typical misconceptions such as exaggerating the number of alternations. We reasoned that remaining regularities would express the algorithmic nature of human thoughts, revealed in the form of specific patterns. Kolmogorov complexity relative to LT^2C^2 passed three expected tests examined here: 1 human sequences were less complex than control PRNG sequences, 2 human sequences were not stationary showing decreasing values of complexity resulting from fatigue 3 each individual showed traces of algorithmic stability since fitting of partial data was more effective to predict subsequent data than average fits. This work extends on previous efforts to combine notions of Kolmogorov complexity theory and algorithmic information theory to psychology, by explicitly proposing a language which may describe the patterns of human thoughts.Received: 12

  6. Ordered perovskites with cationic vacancies. 10. Compounds of type A/sub 2/sup(II)Bsub(1/4)sup(II)Bsub(1/2)sup(III)vacantsub(1/4)Msup(VI)O/sub 6/ equal to A/sub 8/sup(II)Bsup(II)B/sub 2/sup(III)vacantM/sub 4/sup(VI)O/sub 24/ with Asup(II), Bsup(II) = Ba, Sr, Ca and Msup(VI) = U, W

    Energy Technology Data Exchange (ETDEWEB)

    Betz, B; Schittenhelm, H J; Kemmler-Sack, S [Tuebingen Univ. (Germany, F.R.). Lehrstuhl fuer Anorganische Chemie 2

    1982-01-01

    Perovskites of type Ba/sub 8/Bsup(II)B/sub 2/sup(III)vacantU/sub 4/sup(VI)O/sub 24/ show polymorphic phase transformations of order disorder type. An 1:1 ordered orthorhombic HT form is transformed into a higher ordered LT modification with a fourfold cell content (four formula units Ba/sub 8/Bsup(II)B/sub 2/sup(III)vacantU/sub 4/O/sub 24/), compared to cubic 1:1 ordered perovskites A/sub 2/BMO/sub 6/. In the series Ba/sub 8/BaB/sub 2/sup(III)vacantW/sub 4/O/sub 24/ and Sr/sub 8/SrB/sub 2/sup(III)vacantW/sub 4/O/sub 24/ different ordering phenomena are observed. In comparison with 1:1 ordered cubic perovskites A/sub 2/BMO/sub 6/, the cell contains eight formula units A/sub 8/sup(II)Bsup(II) B/sub 2/sup(III)vacantW/sub 4/O/sub 2/4. The higher ordered cells with Usup(VI) and Wsup(VI) are face centered, which has its origin in an ordering of cationic vacancies.

  7. Hepatic Warm Ischemia-Reperfusion-Induced Increase in Pulmonary Capillary Filtration Is Ameliorated by Administration of a Multidrug Resistance-Associated Protein 1 Inhibitor and Leukotriene D4 Antagonist (MK-571) Through Reducing Neutrophil Infiltration and Pulmonary Inflammation and Oxidative Stress in Rats.

    Science.gov (United States)

    Yeh, D Y-W; Yang, Y-C; Wang, J-J

    2015-05-01

    Hepatopulmonary syndrome (HPS) is the major complication subsequent to liver ischemia and reperfusion (I/R) injury after resection or transplantation of liver. Hallmarks of HPS include increases in pulmonary leukotrienes and neutrophil recruitment and infiltrating across capillaries. We aimed to investigate the protective efficacy of MK-571, a multidrug resistance-associated protein 1 inhibitor and leukotriene D4 agonist, against hepatic I/R injury-associated change in capillary filtration. Eighteen Sprague-Dawley male rats were evenly divided into a sham-operated group, a hepatic I/R group, and an MK-571-treated I/R group. MK-571 was administered intraperitoneally 15 min before hepatic ischemia and every 12 hours during reperfusion. Ischemia was conducted by occluding the hepatic artery and portal vein for 30 min, followed by removing the clamps and closing the incision. Forty-eight hours after hepatic ischemia, we assessed the pulmonary capillary filtration coefficient (Kfc) through the use of in vitro-isolated, perfused rat lung preparation. We also measured the lung wet-to-dry weight ratio (W/D) and protein concentration in broncho-alveolar lavage fluid (PCBAL). Lung inflammation and oxidative stress were evaluated by use of tissue tumor necrosis factor (TNF)-α and malondialdehyde levels and lavage differential macrophage and neutrophil cell count. Hepatic I/R injury markedly increased Kfc, W/D, PCBAL, tissue TNF-α level, and differential neutrophil cell count (P < .05). MK-571 treatment reduced neutrophil infiltration and lung inflammation and improved pulmonary capillary filtration, collectively suggesting lung protection. Treatment with MK-571 before and during hepatic ischemia and reperfusion protects lung against pulmonary capillary barrier function impairment through decreasing pulmonary lung inflammation and lavage neutrophils. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Pharmacological inhibition of eicosanoid synthesis and hyperalgesia in yeast-injected rat paws

    International Nuclear Information System (INIS)

    Opas, E.E.; Dallob, A.; Herold, E.; Luell, S.; Humes, J.L.

    1986-01-01

    Brewer's yeast caused an inflammation characterized by edema and hyperalgesia when injected into the hindpaw of a rat. These events were temporally distinct and each was associated with increases of specific arachidonic and oxygenation products. As determined by radioimmunoassay (RIA) on whole paw lipid extracts, the 5-lipoxygenase (5-LO) products, leukotrienes C 4 and D 4 and 5-hydroxyeicosatetraendic acid (5-HETE) were synthesized concurrently with the onset of edema (maximal at 15 minutes after yeast injection). The hyperalgesic phase of the inflammation (3-4 hr after yeast injection) was associated with increased tissue levels of the cyclooxygenase (CO) products, prostaglandin E 2 and thromboxane B 2 (TXB 2 ) as well as increases in levels of the 5-LO products, leukotriene B 4 (LTB 4 ) and 5-HETE. Pharmacological agents modulated the synthesis of eicosanoids and suppressed the hyperalgesic response

  9. Tissue distribution of a leukotriene antagonist 14C-LY170680, following inhalation exposure in the rat

    International Nuclear Information System (INIS)

    Pohland, R.C.; Beck, J.M.; Carlson, K.H.; Herman, D.R.; Hoppes, J.L.; Vavrek, M.T.; Wolff, R.K.

    1991-01-01

    Dissection and whole-body autoradiographic techniques were used to determine the tissue distribution profile of a leukotriene antagonist, 14 C-LY170680, following nose-only inhalation exposure in the rat. Liquid scintillation spectrometry and whole-body autoradiography indicated that highest concentrations of radiocarbon were present in stomach and small intestine at all time points. Radiocarbon reached maximum levels in stomach (2,259 ng-eq/g) and small intestine (2,399 ng-eq/g) 2 to 4 hours postexposure, respectively, and declined with time. In contrast, maximum radiocarbon concentrations in the head (146 ng-eq/g), trachea (408 ng-eq/g), and lung (534 ng-eq/g) occurred at 0 hours postexposure and steadily declined with time. Low concentrations of radiocarbon were detected in the liver ( 14 C-LY170680 were deposited in the head and within the lung following inhalation exposure. However, higher levels of radiocarbon present in the stomach and small intestine suggested significant nasal deposition followed by rapid clearance and ingestion of inhaled radioactive material. Distribution of radiocarbon limited to the respiratory and gastrointestinal tracts demonstrated minimal systemic absorption and exposure over the time course of this study

  10. The use of the laryngeal tube disposable (LT-D) by paramedics during out-of-hospital resuscitation-an observational study concerning ERC guidelines 2005.

    Science.gov (United States)

    Wiese, C H R; Semmel, T; Müller, J U; Bahr, J; Ocker, H; Graf, B M

    2009-02-01

    In the current guidelines of the European Resuscitation Council (ERC), tracheal intubation, as an instrument for securing the airway during resuscitation, has become less important for persons not trained in this method. For those persons, different supraglottic airway devices are recommended by the ERC. The present investigation deals with the application of the laryngeal tube disposable (LT-D) during pre-hospital resuscitation by paramedics. During a period of 2 years (2006-2008), we registered all cardiac arrest situations in which the LT-D had been applied according to the ERC guidelines 2005. Therefore, we investigated one emergency medical system in Germany. During the defined period, 92 resuscitation attempts, recorded on standardised data sheets, were included. The LT-D was used in 46% of all cardiac arrest situations. Overall, the LT-D was successfully inserted in more than 90% of all cases on first attempt. In 95% of all cases, no problems concerning ventilation of the patient were described. As an alternative airway device recommended by the ERC in 2005, the LT-D may enable airway control rapidly and effectively. Additionally, by using the LT-D, a reduced "no-flow-time" and a better outcome may be possible.

  11. Relationship between leukotriene-modifying agent prescriptions dispensed and rate of suicide deaths by county in the US

    Directory of Open Access Journals (Sweden)

    Schumock GT

    2011-09-01

    Full Text Available Glen T Schumock1, Robert D Gibbons2, Todd A Lee1,3,4,6, Min J Joo4, Robert J Valuck5, Leslie T Stayner61Center for Pharmacoeconomic Research, and Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA; 2Center for Health Statistics, and Departments of Medicine and Health Studies, Pritzker School of Medicine, University of Chicago, Chicago, IL, USA; 3Center for Management of Complex Chronic Care, Hines VA Hospital, Hines, IL, USA; 4Section of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA; 5Department of Clinical Pharmacy, School of Pharmacy, University of Colorado, Aurora, CO, USA; 6Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois at Chicago, Chicago, IL, USABackground: The US Food and Drug Administration has issued warnings about a potential link between leukotriene receptor-modifying agents (LTMA and suicide. These warnings are based on case reports and there is controversy about the association. While spontaneous reporting of suicide-related events attributed to LTMA has risen dramatically, these data may be biased by the warnings. The objective of this study was to explore the relationship between LTMA and suicide deaths using event data preceding the Food and Drug Administration warnings.Methods: We conducted a mixed-effects Poisson regression analysis of the association between LTMA prescriptions dispensed and suicide deaths at the county level. Counts of suicide deaths in each US county, stratified by race, age group, gender, and year were obtained from the National Center for Health Statistics for the period January 1, 1999 to December 31, 2006. Counts of LTMA prescriptions dispensed in each US county were obtained from IMS Health Incorporated. The model estimated the overall suicide rate conditional on LTMA use, adjusted for age, gender, race, year

  12. Systems Li2B4O7 (Na2B4O7, K2B4O7)-N2H3H4OH-H2O at 25 deg C

    International Nuclear Information System (INIS)

    Skvortsov, V.G.; Sadetdinov, Sh.V.; Akimov, V.M.; Mitrasov, Yu.N.; Petrova, O.V.; Klopov, Yu.N.

    1994-01-01

    Phase equilibriums in the Li 2 B 4 O 7 (Na 2 B 4 O 7 , K 2 B 4 O 7 )-N 2 H 3 H 4 OH-H 2 O systems were investigated by methods of isothermal solubility, refractometry and PH-metry at 25 deg C for the first time. Lithium and sodium tetraborates was established to form phases of changed composition mM 2 B 4 O 7 ·nN 2 H 3 C 2 H 4 OH·XH 2 O, where M=Li, Na with hydrazine ethanol. K 2 B 4 O 7 ·4H 2 O precipitates in solid phase in the case of potassium salt. Formation of isomorphous mixtures was supported by X-ray diffraction and IR spectroscopy methods

  13. The effect of anti-IgE treatment on in vitro leukotriene release in children with seasonal allergic rhinitis.

    Science.gov (United States)

    Kopp, Matthias Volkmar; Brauburger, Jens; Riedinger, Frank; Beischer, Dorothee; Ihorst, Gabriele; Kamin, Wolfgang; Zielen, Stefan; Bez; Friedrichs, Frank; Von Berg, Andrea; Gerhold, Kerstin; Hamelmann, Eckard; Hultsch; Kuehr, Joachim

    2002-11-01

    Binding of allergens with IgE to the IgE receptors on mast cells and basophils results in the release of inflammatory mediators as sulfidoleukotrienes (SLTs), triggering allergic cascades that result in allergic symptoms, such as asthma and rhinitis. We sought to investigate whether anti-IgE (Oma-lizumab), a humanized monoclonal anti-IgE antibody, in addition to specific immunotherapy (SIT) affects the leukotriene pathway. Ninety-two children (age range, 6-17 years) with sensitization to birch and grass pollens and with seasonal allergic rhinitis were included in a phase III, placebo- controlled, multicenter clinical study. All subjects were randomized to one of 4 treatment groups. Two groups subcutaneously received birch SIT and 2 groups received grass SIT for at least 14 weeks before the start of the birch pollen season. After 12 weeks of SIT titration, placebo or anti-IgE was added for 24 weeks. The primary clinical efficacy variable was symptom load (ie, the sum of daily symptom severity score and rescue medication score during pollen season). Blood samples taken at baseline and at the end of study treatment after the grass pollen season were used for separation of leukocytes in this substudy. After in vitro stimulation of the blood cells with grass and birch pollen allergens, SLT release (LTC4, LTD4, and LTE4) was quantified by using the ELISA technique. Before the study treatment, SLT release to birch and grass pollen exposure did not differ significantly among the 4 groups. Under treatment with anti-IgE + SIT-grass (n = 23), a lower symptom load occurred during the pollen season compared to placebo + SIT-grass (n = 24, P =.012). The same applied to both groups receiving birch SIT (n = 23 and n = 22, respectively; P =.03). At the end of treatment, the combination of anti-IgE plus grass SIT, as well as anti-IgE plus birch SIT, resulted in significantly lower SLT release after stimulation with the corresponding allergen (416 ng/L [5th-95th percentile, 1

  14. Mastering Autodesk Inventor 2014 and Autodesk Inventor LT 2014

    CERN Document Server

    Waguespack, Curtis

    2013-01-01

    An Autodesk Official Press guide to the powerful mechanical design software Autodesk Inventor has been used to design everything from cars and airplanes to appliances and furniture. This comprehensive guide to Inventor and Inventor LT features real-world workflows and work environments, and is packed with practical tutorials that focus on teaching Inventor tips, tricks, and techniques. Additionally, you can download datasets to jump in and practice on any exercise. This reference and tutorial explains key interface conventions, capabilities, tools, and techniques, including desi

  15. 76 FR 441 - Airworthiness Directives; Airbus Model A300 B4-600, B4-600R, and F4-600R Series Airplanes, and...

    Science.gov (United States)

    2011-01-05

    ... Airworthiness Directives; Airbus Model A300 B4-600, B4-600R, and F4-600R Series Airplanes, and Model C4-605R...-622, B4-605R, B4-622R, F4-605R, F4-622R, and C4-605R Variant F airplanes, certificated in any category...

  16. 76 FR 28914 - Airworthiness Directives; Airbus Model A300 B4-600, B4-600R, and F4-600R Series Airplanes, and...

    Science.gov (United States)

    2011-05-19

    ... B4-600, B4-600R, and F4-600R Series Airplanes, and Model C4-605R Variant F Airplanes (Collectively... B4-605R and B4-622R airplanes; A300 F4-605R and F4-622R airplanes; A300 C4-605R Variant F airplanes...

  17. 75 FR 76926 - Airworthiness Directives; Airbus Model A300 B4-600, B4-600R, and F4-600R Series Airplanes, and...

    Science.gov (United States)

    2010-12-10

    ... Airworthiness Directives; Airbus Model A300 B4-600, B4-600R, and F4-600R Series Airplanes, and Model C4-605R... airplanes; Model A300 B4-605R and B4-622R airplanes; Model A300 F4-605R and F4-622R airplanes; Model A300 C4...

  18. 76 FR 42029 - Airworthiness Directives; Airbus Model A300 B4-600, B4-600R, and F4-600R Series Airplanes, and...

    Science.gov (United States)

    2011-07-18

    ... Airworthiness Directives; Airbus Model A300 B4-600, B4-600R, and F4-600R Series Airplanes, and Model A300 C4... A300 B4-605R and B4-622R airplanes, Model A300 F4-605R and F4-622R airplanes, and Model A300 C4- [[Page...

  19. 76 FR 39248 - Airworthiness Directives; Airbus Model A300 B4-600, B4-600R, and F4-600R Series Airplanes, and...

    Science.gov (United States)

    2011-07-06

    ... Airworthiness Directives; Airbus Model A300 B4-600, B4-600R, and F4-600R Series Airplanes, and Model C4-605R... B4-605R and B4-622R airplanes; Model A300 F4-605R and F4-622R airplanes; Model A300 C4-605R Variant F...

  20. 75 FR 28480 - Airworthiness Directives; Airbus Model A300 Series Airplanes; Model A300 B4-600, B4-600R, F4-600R...

    Science.gov (United States)

    2010-05-21

    ... Airworthiness Directives; Airbus Model A300 Series Airplanes; Model A300 B4-600, B4-600R, F4-600R Series..., B4-622, B4- 605R, B4-622R, F4-605R, F4-622R, and C4-605R Variant F airplanes; and Model A310-203...

  1. The Akashi Kaikyo Bridge and the Storebælt Bridge

    DEFF Research Database (Denmark)

    Gimsing, Niels Jørgen

    1999-01-01

    With the completion of the Akashi Kaikyo Bridge and the Storebælt East Bridge the development of the suspension bridge technology in the 20th century has manifested itself in two impressive structures. With the present echnology may bridges of similar (and also more modest) dimensions...... will undoubtedly be built far into the next century. For bridges going beyond the spans of existing bridges it is, however, likely that new concepts will be developed....

  2. Autodesk Inventor 2013 and Autodesk Inventor LT 2013 essentials

    CERN Document Server

    Tremblay, Thom

    2012-01-01

    Get up to speed with Autodesk Inventor, the leading manufacturing design program This Autodesk Official Training Guide thoroughly covers the fundamentals of Autodesk Inventor 2013 and Inventor LT 2013. Focusing on basics such as using the interface, creating parts and assemblies, applying standards and styles, creating 2D drawings from 3D data, and more, it teaches you everything you need to become quickly productive with the software. Whether you're a new student learning CAD, preparing for certification, or updating your Inventor skills, this is the fast, thorough grounding you need. Featu

  3. A new avian fauna from the early-middle Eocene Lillebælt Clay Formation of Denmark

    DEFF Research Database (Denmark)

    Lindow, Bent Erik Kramer

    A number of hitherto undescribed fossil bird remains have been recovered from the Lillebælt Clay Formation of central Denmark, which is early-middle Eocene in age (~50 to 43 mya). The core of the material consists of fossils acquired through the Danish ‘Danekræ' fossil treasure trove legislation......, a member of the extinct 'pseudo-toothed birds' and the first representative of this group known from Denmark. Other taxa present include remains of Lithornithidae and a new taxon possessing a massive, psittacid-like beak. The Lillebælt Clay Formation birds are temporally placed just after the Early Eocene...

  4. 76 FR 18960 - Airworthiness Directives; Airbus Model A300 B4-600, B4-600R, and F4-600R Series Airplanes, and...

    Science.gov (United States)

    2011-04-06

    ... B4-600, B4-600R, and F4-600R Series Airplanes, and Model C4-605R Variant F Airplanes (Collectively... July 20, 2005; have been performed in service. (2) Airbus Model A300 B4-605R, B4-622R, F4-605R, and F4... C4-600R, and A300 F4-600R series airplanes (fitted with a trim tank), all serial numbers, except...

  5. Düşey Toplum Kuramı Yaklaşımıyla Japon Çalışma Kültürünü Anlamak

    OpenAIRE

    Aca, Zeynep

    2015-01-01

    Japon çalışma kültürünün temel felsefesini anlayabilmenin yolu, Japon toplumunun kültürel özelliklerini anlayabilmekten geçmektedir. Ancak kültürü oluşturan her bir özellik elbetteki Japon çalışma kültürünü aynı ölçüde etkilememektedir. İşte bu noktadan hareketle, bu çalışmada, Japon çalışma kültürü, Japon çalışma kültürünün temel felsefi belirleyicilerinden biri olduğunu düşündüğümüz ve Nakane tarafından Düşey Toplum Kuramı olarak adlandırılan Japon aile yapısı ekseninde ele alınmaya çalışıl...

  6. Alkaline pH Is a signal for optimal production and secretion of the heat labile toxin, LT in enterotoxigenic Escherichia coli (ETEC.

    Directory of Open Access Journals (Sweden)

    Lucia Gonzales

    Full Text Available Enterotoxigenic Escherichia coli (ETEC cause secretory diarrhea in children and travelers to endemic areas. ETEC spreads through the fecal-oral route. After ingestion, ETEC passes through the stomach and duodenum before it colonizes the lower part of the small intestine, exposing bacteria to a wide range of pH and environmental conditions. This study aimed to determine the impact of external pH and activity of the Cyclic AMP receptor protein (CRP on the regulation of production and secretion of heat labile (LT enterotoxin. ETEC strain E2863wt and its isogenic mutant E2863ΔCRP were grown in LBK media buffered to pH 5, 7 and 9. GM1 ELISA, cDNA and cAMP analyses were carried out on bacterial pellet and supernatant samples derived from 3 and 5 hours growth and from overnight cultures. We confirm that CRP is a repressor of LT transcription and production as has been shown before but we show for the first time that CRP is a positive regulator of LT secretion both in vitro and in vivo. LT secretion increased at neutral to alkaline pH compared to acidic pH 5 where secretion was completely inhibited. At pH 9 secretion of LT was optimal resulting in 600 percent increase of secreted LT compared to unbuffered LBK media. This effect was not due to membrane leakage since the bacteria were viable at pH 9. The results indicate that the transition to the alkaline duodenum and/or exposure to high pH close to the epithelium as well as activation of the global transcription factor CRP are signals that induce secretion of the LT toxin in ETEC.

  7. Sewage sludge amendment and inoculation with plant-parasitic nematodes do not facilitate the internalization of Salmonella Typhimurium LT2 in lettuce plants.

    Science.gov (United States)

    Fornefeld, Eva; Baklawa, Mohamed; Hallmann, Johannes; Schikora, Adam; Smalla, Kornelia

    2018-05-01

    Contamination of fruits and vegetables with Salmonella is a serious threat to human health. In order to prevent possible contaminations of fresh produce it is necessary to identify the contributing ecological factors. In this study we investigated whether the addition of sewage sludge or the presence of plant-parasitic nematodes foster the internalization of Salmonella enterica serovar Typhimurium LT2 into lettuce plants, posing a potential threat for human health. Greenhouse experiments were conducted to investigate whether the amendment of sewage sludge to soil or the presence of plant-parasitic nematodes Meloidogyne hapla or Pratylenchus crenatus promote the internalization of S. Typhimurium LT2 from soil into the edible part of lettuce plants. Unexpectedly, numbers of cultivable S. Typhimurium LT2 decreased faster in soil with sewage sludge than in control soil but not in root samples. Denaturing gradient gel electrophoresis analysis revealed shifts of the soil bacterial communities in response to sewage sludge amendment and time. Infection and proliferation of nematodes inside plant roots were observed but did not influence the number of cultivable S. Typhimurium LT2 in the root samples or in soil. S. Typhimurium LT2 was not detected in the leaf samples 21 and 49 days after inoculation. The results indicate that addition of sewage sludge, M. hapla or P. crenatus to soil inoculated with S. Typhimurium LT2 did not result in an improved survival in soil or internalization of lettuce plants. Copyright © 2017. Published by Elsevier Ltd.

  8. MaLT - Combined Motor and Language Therapy Tool for Brain Injury Patients Using Kinect.

    Science.gov (United States)

    Wairagkar, Maitreyee; McCrindle, Rachel; Robson, Holly; Meteyard, Lotte; Sperrin, Malcom; Smith, Andy; Pugh, Moyra

    2017-03-23

    The functional connectivity and structural proximity of elements of the language and motor systems result in frequent co-morbidity post brain injury. Although rehabilitation services are becoming increasingly multidisciplinary and "integrated", treatment for language and motor functions often occurs in isolation. Thus, behavioural therapies which promote neural reorganisation do not reflect the high intersystem connectivity of the neurologically intact brain. As such, there is a pressing need for rehabilitation tools which better reflect and target the impaired cognitive networks. The objective of this research is to develop a combined high dosage therapy tool for language and motor rehabilitation. The rehabilitation therapy tool developed, MaLT (Motor and Language Therapy), comprises a suite of computer games targeting both language and motor therapy that use the Kinect sensor as an interaction device. The games developed are intended for use in the home environment over prolonged periods of time. In order to track patients' engagement with the games and their rehabilitation progress, the game records patient performance data for the therapist to interrogate. MaLT incorporates Kinect-based games, a database of objects and language parameters, and a reporting tool for therapists. Games have been developed that target four major language therapy tasks involving single word comprehension, initial phoneme identification, rhyme identification and a naming task. These tasks have 8 levels each increasing in difficulty. A database of 750 objects is used to programmatically generate appropriate questions for the game, providing both targeted therapy and unique gameplay every time. The design of the games has been informed by therapists and by discussions with a Public Patient Involvement (PPI) group. Pilot MaLT trials have been conducted with three stroke survivors for the duration of 6 to 8 weeks. Patients' performance is monitored through MaLT's reporting facility

  9. 76 FR 6581 - Airworthiness Directives; Airbus Model A300 B4-600, B4-600R, and F4-600R Series Airplanes, and...

    Science.gov (United States)

    2011-02-07

    ... B4-600, B4-600R, and F4-600R Series Airplanes, and Model C4-605R Variant F Airplanes (Collectively...-605R, B4-622R, F4-605R, F4-622R, and C4-605R Variant F airplanes, certificated in any category, all...

  10. Side Effects of Leukotriene Receptor Antagonists in Asthmatic Children.

    Science.gov (United States)

    Erdem, Semiha Bahceci; Nacaroglu, Hikmet Tekin; Unsal Karkiner, Canan Sule; Gunay, Ilker; Can, Demet

    2015-10-01

    Leukotriene receptor antagonists (LTRAs) are drugs which have been widely used more than ten years. As the use of LTRAs increases, our knowledge with respect to their side effects increases as well. The objective of our study was to evaluat the observed side effects of LTRAs used in patients with astma. 1024 patients treated only with LTRAs owing to asthma or early wheezing were included in the study for a five-year period. The observed side effects of LTRAs in these patients were retrospectively investigated. The side effects were divided into two parts as psychiatric and non-psychiatric. Among the 1024 cases included in the study, 67.5% of the patients out of 41 with side effects were male, 32.5% were female and the average age was 6.5 years. The rate of patients with asthma was 63.41% and 36.58% of the patients had early wheezing. It was determined that sex, age and diagnosis (early wheezing or asthma) of the patients were ineffective in the emergence of side effects. The average period for the emergence of side effects was the first month. It was observed that hyperactivity was the most frequently observed psychiatric side effect and that abdominal pain was the non-psychiatric side effect. The side effects of LTRAs were common in children. Therefore, patients must be informed at the beginning of the treatment and they must be evaluated at certain intervals.

  11. Raman evidence of the formation of LT-LiCoO 2 thin layers on NiO in molten carbonate at 650°C

    Science.gov (United States)

    Mendoza, L.; Baddour-Hadjean, R.; Cassir, M.; Pereira-Ramos, J. P.

    2004-03-01

    The structural evolution of thin layers of Co 3O 4 elaborated on nickel-based substrates in the Li 2CO 3-Na 2CO 3 carbonate eutectic at 650 °C as a function of time immersion is reported. Raman microspectrometry has been applied in order to provide more information on the nature of the protective cobalt oxide layers. The typical Raman fingerprint of the LT-LiCoO 2 compound has been obtained, with four well defined bands at 449, 484, 590 and 605 cm -1, while XRD data are unable to distinguish the layered phase (HT) from the spinel one (LT). The mechanical stability of such films does not exceed 10 h in direct contact with the molten carbonate bulk at 650 °C; nevertheless, these conditions are much more corrosive than in a molten carbonate fuel cell (MCFC).

  12. Karzai nõuab USA-lt võitu, ähvardades muidu rahu teha / Heiki Suurkask

    Index Scriptorium Estoniae

    Suurkask, Heiki, 1972-

    2008-01-01

    Afganistani president Hamid Karzai nõuab USA-lt ajakava selle kohta, millal NATO kavatseb Talibani üle võidu saavutada. Afganistanis visiidil viibinud USA president George W. Bush avaldas toetust Barack Obama kavale keskenduda veelgi enam Afganistanis sõdimisele

  13. Interface interaction in the B4C/(Fe-B-C) system

    International Nuclear Information System (INIS)

    Aizenshtein, M.; Mizrahi, I.; Froumin, N.; Hayun, S.; Dariel, M.P.; Frage, N.

    2008-01-01

    The wetting behavior in the B 4 C/(Fe-C-B) system was investigated in order to clarify the role of Fe additions on the sinterability of B 4 C. Iron and its alloys with C and B react with the boron carbide substrate and form a reaction zone consisting of a fine mixture of FeB and graphite. The apparent contact angles are relatively low for the alloys with a moderate concentration of the boron and carbon and allow liquid phase sintering to occur in the B 4 C-Fe mixtures. A dilatometric study of the sintering kinetics confirms that liquid phase sintering actually takes place and leads to improved mass transfer. A thermodynamic analysis of the ternary Fe-B-C system allows accounting for the experimental observations

  14. Combination of Dll4/Notch and Ephrin-B2/EphB4 targeted therapy is highly effective in disrupting tumor angiogenesis

    International Nuclear Information System (INIS)

    Djokovic, Dusan; Gill, Parkash S; Duarte, Antonio; Trindade, Alexandre; Gigante, Joana; Badenes, Marina; Silva, Lilliana; Liu, Ren; Li, Xiuqing; Gong, Ming; Krasnoperov, Valery

    2010-01-01

    Dll4/Notch and Ephrin-B2/EphB4 pathways play critical roles in tumor vessel development and maturation. This study evaluates the efficacy of the inhibition of both signaling pathways, alone and in combination, in reducing the growth of an autochthonous mouse tumor and assesses potential adverse effects. We used the transgenic RIP1-Tag2 tumor model to study the effects of 1) inhibition of Dll4/Notch by either Dll4 allelic deletion or use of a soluble extracellular Dll4 (sDll4), 2) inhibition of Ephrin-B2/EphB4 signaling by a soluble extracellular EphB4 fused to albumin (sEphB4-Alb), and 3) inhibition of both pathways by sEphB4-Alb combined with either Dll4 allelic deletion or sDll4. To investigate adverse effects, we used inducible endothelial-specific Dll4 knock-out mice, treated with sEphB4-Alb, and carried out histopathological analysis. Dll4 allele deletion or soluble Dll4 treatment resulted in increased tumor vessel density, reduced mural cell recruitment and vessel perfusion which resulted in reduced tumor size. The soluble EphB4 instead reduced vessel density and vessel perfusion, leading to reduction of tumor size. Greater efficacy was observed when sEphB4-Alb was combined with either Dll4 allele deletion or sDll4 in regards to tumor size, vessel perfusion and mural cell recruitment. Induced endothelial specific Dll4 loss-of-function caused hepatic vascular alterations, which were prevented by concomitant sEphB4-Alb treatment. Combination targeting of Dll4/Notch and Ephrin-B2/EphB4 has potential for clinical investigation, providing cumulative efficacy and increased safety over Dll4/Notch inhibition alone

  15. Re-evaluation of Ipsilateral Radiation for T1-T2N0-N2b Tonsil Carcinoma at the Princess Margaret Hospital in the Human Papillomavirus Era, 25 Years Later

    International Nuclear Information System (INIS)

    Huang, Shao Hui; Waldron, John; Bratman, Scott V.; Su, Jie; Kim, John; Bayley, Andrew; Cho, John; Giuliani, Meredith; Hope, Andrew; Ringash, Jolie; Hansen, Aaron; Almeida, John R. de; Goldstein, David; Perez-Ordonez, Bayardo; Weinreb, Ilan; Tong, Li; Xu, Wei; O'Sullivan, Brian

    2017-01-01

    Purpose: To report the outcome of ipsilateral radiation therapy (RT) in human papillomavirus (HPV)-positive (HPV+) patients and HPV-negative (HPV−) patients with T1-T2N0-N2b tonsillar cancer treated 25 years after our initial historical cohort. Methods and Materials: Patients with T1-T2N0-N2b tonsillar cancer who received ipsilateral RT or bilateral RT between 1999 and 2014 were reviewed. Overall survival (OS), local control (LC), regional control (RC), and grade 3 to 4 late toxicity (LT) were compared between ipsilateral RT and bilateral RT within HPV+ and HPV− patients, separately. Results: HPV status was ascertained in 379/427 (88%) consecutive patients (ipsilateral RT: 62 HPV+, 34 HPV−; bilateral RT: 240 HPV+ 240, 41 HPV−). The proportion of ipsilateral RT by N category for HPV+ and HPV− patients were as follows: N0: 24/37 (65%) versus 28/48 (74%); N1: 21/49 (43%) versus 4/9 (44%); N2a: 10/39 (26%) versus 1/4 (25%); and N2b: 7/177 (4%) versus 1/24 (4%), respectively. Of the patients receiving ipsilateral RT, 94/96 (98%) were treated with RT alone. The median follow-up time was 5.03 years. The respective 5-year rates of OS, LC, RC, and LT were similar between ipsilateral RT and bilateral RT for the HPV+ patients (OS: 89% vs 87%, P=.55; LC: 97% vs 98%, P=.65; RC: 98% vs 97%, P=.27; LT: 17% vs 12%, P=.83) and HPV− patients (OS: 63% vs 48%, P=.27; LC: 90% vs 80%, P=.19; RC: 94% vs 83%, P=.14; LT: 15% vs 22%, P=.36). Of the 96 patients receiving ipsilateral RT, contralateral neck failure (CNF) occurred in 1/52 HPV+ patients and 1/34 HPV− patients. The 5-year CNF rates were 2% (95% CI: 1-9) (HPV+: 2% [0-14]; HPV−: 3% [0-21], P=.66). Five local failures (2 HPV+; 3 HPV−) and no distant failures were seen. The 5-year rates of LC, RC, and LT were 97% versus 90% (P=.24), 98% versus 94% (P=.25), and 18% versus 15% (P=.75) for the HPV+ and HPV− cohorts, respectively. Osteoradionecrosis occurred in 9 patients: 6/47 (13%) treated with conventional RT

  16. Re-evaluation of Ipsilateral Radiation for T1-T2N0-N2b Tonsil Carcinoma at the Princess Margaret Hospital in the Human Papillomavirus Era, 25 Years Later

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Shao Hui, E-mail: shaohui.huang@rmp.uhn.on.ca [Department of Radiation Oncology, The Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Waldron, John [Department of Radiation Oncology, The Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Department of Otolaryngology—Head & Neck Surgery, The Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Bratman, Scott V. [Department of Radiation Oncology, The Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Su, Jie [Department of Biostatistics, The Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Kim, John; Bayley, Andrew; Cho, John; Giuliani, Meredith; Hope, Andrew; Ringash, Jolie [Department of Radiation Oncology, The Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Hansen, Aaron [Division of Medical Oncology, The Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Almeida, John R. de; Goldstein, David [Department of Otolaryngology—Head & Neck Surgery, The Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Perez-Ordonez, Bayardo; Weinreb, Ilan [Department of Pathology, The Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Tong, Li [Department of Radiation Oncology, The Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Xu, Wei [Department of Biostatistics, The Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); O' Sullivan, Brian [Department of Radiation Oncology, The Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Department of Otolaryngology—Head & Neck Surgery, The Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada)

    2017-05-01

    Purpose: To report the outcome of ipsilateral radiation therapy (RT) in human papillomavirus (HPV)-positive (HPV+) patients and HPV-negative (HPV−) patients with T1-T2N0-N2b tonsillar cancer treated 25 years after our initial historical cohort. Methods and Materials: Patients with T1-T2N0-N2b tonsillar cancer who received ipsilateral RT or bilateral RT between 1999 and 2014 were reviewed. Overall survival (OS), local control (LC), regional control (RC), and grade 3 to 4 late toxicity (LT) were compared between ipsilateral RT and bilateral RT within HPV+ and HPV− patients, separately. Results: HPV status was ascertained in 379/427 (88%) consecutive patients (ipsilateral RT: 62 HPV+, 34 HPV−; bilateral RT: 240 HPV+ 240, 41 HPV−). The proportion of ipsilateral RT by N category for HPV+ and HPV− patients were as follows: N0: 24/37 (65%) versus 28/48 (74%); N1: 21/49 (43%) versus 4/9 (44%); N2a: 10/39 (26%) versus 1/4 (25%); and N2b: 7/177 (4%) versus 1/24 (4%), respectively. Of the patients receiving ipsilateral RT, 94/96 (98%) were treated with RT alone. The median follow-up time was 5.03 years. The respective 5-year rates of OS, LC, RC, and LT were similar between ipsilateral RT and bilateral RT for the HPV+ patients (OS: 89% vs 87%, P=.55; LC: 97% vs 98%, P=.65; RC: 98% vs 97%, P=.27; LT: 17% vs 12%, P=.83) and HPV− patients (OS: 63% vs 48%, P=.27; LC: 90% vs 80%, P=.19; RC: 94% vs 83%, P=.14; LT: 15% vs 22%, P=.36). Of the 96 patients receiving ipsilateral RT, contralateral neck failure (CNF) occurred in 1/52 HPV+ patients and 1/34 HPV− patients. The 5-year CNF rates were 2% (95% CI: 1-9) (HPV+: 2% [0-14]; HPV−: 3% [0-21], P=.66). Five local failures (2 HPV+; 3 HPV−) and no distant failures were seen. The 5-year rates of LC, RC, and LT were 97% versus 90% (P=.24), 98% versus 94% (P=.25), and 18% versus 15% (P=.75) for the HPV+ and HPV− cohorts, respectively. Osteoradionecrosis occurred in 9 patients: 6/47 (13%) treated with conventional RT

  17. Development of an ErbB4 monoclonal antibody that blocks neuregulin-1-induced ErbB4 activation in cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Okazaki, Shogo [Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan); Nakatani, Fumi [Cell Biology Laboratory, Department of Pharmaceutical Sciences, Faculty of Pharmacy, Kinki University, Higashiosaka, Osaka 577-8502 Japan (Japan); Masuko, Kazue; Tsuchihashi, Kenji [Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan); Ueda, Shiho; Masuko, Takashi [Cell Biology Laboratory, Department of Pharmaceutical Sciences, Faculty of Pharmacy, Kinki University, Higashiosaka, Osaka 577-8502 Japan (Japan); Saya, Hideyuki [Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan); Nagano, Osamu, E-mail: osmna@sb3.so-net.ne.jp [Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan)

    2016-01-29

    The use of monoclonal antibodies (mAbs) for cancer therapy is one of the most important strategies for current cancer treatment. The epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases, which regulates cancer cell proliferation, survival, and migration, is a major molecular target for antibody-based therapy. ErbB4/HER4, which contains a ligand-binding extracellular region, is activated by several ligands, including neuregulins (NRGs), heparin-binding EGF-like growth factor, betacellulin and epiregulin. Although there are clinically approved antibodies for ErbB1 and ErbB2, there are no available therapeutic mAbs for ErbB4, and it is not known whether ErbB4 is a useful target for antibody-based cancer therapy. In this study, we developed an anti-ErbB4 mAb (clone P6-1) that suppresses NRG-dependent activation of ErbB4 and examined its effect on breast cancer cell proliferation in the extracellular matrix. - Highlights: • We newly generated four clones of human ErbB4 specific mAb. • ErbB4 mAb clone P6-1 blocks ErbB4 phosphorylation induced by NRG-1. • ErbB4 mAb clone P6-1 suppresses NRG-1-promoted breast cancer cells proliferation on three dimensional culture condition.

  18. Development of an ErbB4 monoclonal antibody that blocks neuregulin-1-induced ErbB4 activation in cancer cells

    International Nuclear Information System (INIS)

    Okazaki, Shogo; Nakatani, Fumi; Masuko, Kazue; Tsuchihashi, Kenji; Ueda, Shiho; Masuko, Takashi; Saya, Hideyuki; Nagano, Osamu

    2016-01-01

    The use of monoclonal antibodies (mAbs) for cancer therapy is one of the most important strategies for current cancer treatment. The epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases, which regulates cancer cell proliferation, survival, and migration, is a major molecular target for antibody-based therapy. ErbB4/HER4, which contains a ligand-binding extracellular region, is activated by several ligands, including neuregulins (NRGs), heparin-binding EGF-like growth factor, betacellulin and epiregulin. Although there are clinically approved antibodies for ErbB1 and ErbB2, there are no available therapeutic mAbs for ErbB4, and it is not known whether ErbB4 is a useful target for antibody-based cancer therapy. In this study, we developed an anti-ErbB4 mAb (clone P6-1) that suppresses NRG-dependent activation of ErbB4 and examined its effect on breast cancer cell proliferation in the extracellular matrix. - Highlights: • We newly generated four clones of human ErbB4 specific mAb. • ErbB4 mAb clone P6-1 blocks ErbB4 phosphorylation induced by NRG-1. • ErbB4 mAb clone P6-1 suppresses NRG-1-promoted breast cancer cells proliferation on three dimensional culture condition.

  19. Esnek ve Rijit Yol Üst Yapılarında Gürültü Seviyelerinin Eş Zamanlı Ölçümü ve Analizi

    Directory of Open Access Journals (Sweden)

    Hakan Yıldırım

    2014-06-01

    Full Text Available Beton yollar dünyada yaygın olarak kullanılmasına karşın ülkemizde gelişim gösterememiş, bu nedenle de genel olarak bitümlü sıcak karışım asfalt yollar tercih edilmiştir.Bu çalışmada, Türkiye'de yaygın olarak kullanılan bitümlü sıcak karışım asfalt yollar ve henüz yaygınlaşmamış olan beton yollar arasında gürültü seviyeleri yönünden bir karşılaştırma yapılmıştır. Bunun için Afyonkarahisar-Emirdağ arasında inşa edilmiş 2 km'lik beton yol ile bu yolun devamı olan bitümlü sıcak karışım asfalt yol arasındaki geçiş noktası çalışma koridoru olarak kullanılmıştır.Bu koridordaki beton yol ve bitümlü sıcak karışım asfalt yolun kenarlarına, ses girişimlerini en aza indirecek şekilde, ayrı ayrı gürültü ölçüm cihazı ve kamera düzenekleri yerleştirilmiş, yol yapım malzemesine bağlı olarak değişen gürültü seviyeleri eş zamanlı olarak kaydedilmiş, bulunan değerler analiz edilerek kaplama türleri ile gürültü seviyeleri arasındaki ilişki araştırılmıştır. Bu aşamada, kurulan düzenekler arasındaki mesafe trafik yoğunluğunun ve akış hızının değişimini engellemek için mümkün olduğunca kısa tutulmuştur.Yapılan ölçüm ve analizler sonunda beton yolların bitümlü sıcak karışım asfalt yollara göre ortalama gürültü seviyesinin aynı taşıt kompozisyonu ve trafik hacmi için yaklaşık 4 dB(A daha düşük olduğu ortaya konmuş ve ülkemizde de beton yolların gelişim göstermesi gerektiği vurgulanmıştır.

  20. The superfamily of C3b/C4b-binding proteins

    DEFF Research Database (Denmark)

    Kristensen, Torsten; D'Eustachio, P; Ogata, R T

    1987-01-01

    The determination of primary structures by amino acid and nucleotide sequencing for the C3b-and/or C4b-binding proteins H, C4BP, CR1, B, and C2 has revealed the presence of a common structural element. This element is approximately 60 amino acids long and is repeated in a tandem fashion, commencing...... at the amino-terminal end of each molecule. Two other complement components, C1r and C1s, have two of these repeating units in the carboxy-terminal region of their noncatalytic A chains. Three noncomplement proteins, beta 2-glycoprotein I (beta 2I), the interleukin 2 receptor (IL 2 receptor), and the b chain...... of factor XIII, have 4, 2 and 10 of these repeating units, respectively. These proteins obviously belong to the above family, although there is no evidence that they interact with C3b and/or C4b. Human haptoglobin and rat leukocyte common antigen also contain two and three repeating units, respectively...

  1. [Treatment of ASS-Associated Polyposis (ASSAP) with a cysteinyl leukotriene receptor antagonist - a prospective drug study on its antiinflammatory effects].

    Science.gov (United States)

    Grundmann, T; Töpfner, M

    2001-10-01

    In a high rate of cases with recurrent polyposis an association with ASS-intolerance is detectable despite missing pulmonary symptoms. New examinations of a disturbed arachidonic acid metabolism lead to the development of new therapeutical options. Treatment with leukotriene-receptor antogonists (LTA) showed primarily good results in therapy of ASS-associated asthma. 18 patients with ASS-intolerance trias - diagnosed by oral provocation - were treated with the LTA Montelukast, after undergoing sinus surgery. Patients underwent a diagnostic pathway of provocation including four groups: recurrent chronic sinusitis, excessive polyposis, polyposis associated with asthma and anaphylactic symptoms after oral ASS-intake. Clinically we examined the following parameters periodically after sinus surgery: nasal and pulmonal symptoms by scoring levels, recurrency of polypoid hyperplasia by endoscopic follow-ups and serum ECP-levels. To evaluate antiinflammatory tissue effects of LTA EG1/EG2 labelled cells and cytokine levels of Interleukin 5 in mucosa samples of the lower turbinate were analysed under LTA-therapy. Under therapy with LTA we saw a beneficial effect on nasal and pulmonary symptoms and a significant reduction of recurrent polyposis in endoscopic examinations in relation to the untreated group. Results were proven by a permanent reduction of serum ECP-level. A reduction of the rate of EG2-positive cells according to decreased Interleukin 5 levels in the nasal mucosa unter LTA-treatment assumed antiinflammatory effects on ASS-associated polyposis. We could demonstrate antiinflammatory effects of Leukotriene-Receptor-Antagonists primarily during postoperative treatment of patients with ASS-associated nasal polyps.

  2. Combustion of Na2B4O7 + Mg + C to synthesis B4C powders

    International Nuclear Information System (INIS)

    Jiang Guojian; Xu Jiayue; Zhuang Hanrui; Li Wenlan

    2009-01-01

    Boron carbide powder was fabricated by combustion synthesis (CS) method directly from mixed powders of borax (Na 2 B 4 O 7 ), magnesium (Mg) and carbon. The adiabatic temperature of the combustion reaction of Na 2 B 4 O 7 + 6 Mg + C was calculated. The control of the reactions was achieved by selecting reactant composition, relative density of powder compact and gas pressure in CS reactor. The effects of these different influential factors on the composition and morphologies of combustion products were investigated. The results show that, it is advantageous for more Mg/Na 2 B 4 O 7 than stoichiometric ratio in Na 2 B 4 O 7 + Mg + C system and high atmosphere pressure in the CS reactor to increase the conversion degree of reactants to end product. The final product with the minimal impurities' content could be fabricated at appropriate relative density of powder compact. At last, boron carbide without impurities could be obtained after the acid enrichment and distilled water washing.

  3. Granzyme B mediated function of Parvovirus B19-specific CD4+ T cells

    Science.gov (United States)

    Kumar, Arun; Perdomo, Maria F; Kantele, Anu; Hedman, Lea; Hedman, Klaus; Franssila, Rauli

    2015-01-01

    A novel conception of CD4+ T cells with cytolytic potential (CD4+ CTL) is emerging. These cells appear to have a part in controlling malignancies and chronic infections. Human parvovirus B19 can cause a persistent infection, yet no data exist on the presence of B19-specific CD4+ CTLs. Such cells could have a role in the pathogenesis of some autoimmune disorders reported to be associated with B19. We explored the cytolytic potential of human parvovirus B19-specific T cells by stimulating peripheral blood mononuclear cell (PBMC) with recombinant B19-VP2 virus-like particles. The cytolytic potential was determined by enzyme immunoassay-based quantitation of granzyme B (GrB) and perforin from the tissue culture supernatants, by intracellular cytokine staining (ICS) and by detecting direct cytotoxicity. GrB and perforin responses with the B19 antigen were readily detectable in B19-seropositive individuals. T-cell depletion, HLA blocking and ICS experiments showed GrB and perforin to be secreted by CD4+ T cells. CD4+ T cells with strong GrB responses were found to exhibit direct cytotoxicity. As anticipated, ICS of B19-specific CD4+ T cells showed expected co-expression of GrB, perforin and interferon gamma (IFN-γ). Unexpectedly, also a strong co-expression of GrB and interleukin 17 (IL-17) was detected. These cells expressed natural killer (NK) cell surface marker CD56, together with the CD4 surface marker. To our knowledge, this is the first report on virus-specific CD4+ CTLs co-expressing CD56 antigen. Our results suggest a role for CD4+ CTL in B19 immunity. Such cells could function within both immune regulation and triggering of autoimmune phenomena such as systemic lupus erythematosus (SLE) or rheumatoid arthritis. PMID:26246896

  4. Pc 4-5 pulsations in the electric field at geostationary orbit (GEOS 2) triggered by sudden storm commencements

    International Nuclear Information System (INIS)

    Laakso, H.; Schmidt, R.

    1989-01-01

    A frequently observed feature in the electric field data on board GEOS 2 is the sudden occurrence of large-amplitude Pc 4-5 waves lasting from a few tens of minutes up to a few hours. For the events the authors have chosen it was found that the large-amplitude events (≥ 2 mV/m) are often accompanied by magnetic field data containing the signature of a compression of the magnetosphere. The occurrence of the compression coincides with the recording of an ssc (sudden storm commencement) on ground. The dc electric field measurements suggest that the Ex B/B 2 drift rapidly and temporarily rotates into a tailward plasma drift at 6.6 R E . The transient disturbances of the magnetopause also changed the widely scattered frequency distribution of the nearly always present fluctuations in the Pc 4-5 range into a narrow-band distribution, with frequently large amplitudes, after the occurrence of the ssc. The frequency distribution reveals a weak dependence on the local time such that the frequencies are close to 4 mHz near noon and abut 3 mHz near dawn and dusk. The rotational sense of polarization is left-handed between 0200 and 1200 LT and right-handed between 1400 and 2200 LT; a transition region exists between 1200 and 1400 LT. The authors argue that the transverse waves are the fundamental modes of the field line resonances while the compressional modes might be the fundamental modes and the second harmonics of the cavity resonances or the plasmasphere modes

  5. AutoCAD 2012 and AutoCAD LT 2012 Bible

    CERN Document Server

    Finkelstein, Ellen

    2011-01-01

    The latest version of this perennial favorite, in-depth, reference-tutorial This top-selling book has been updated by AutoCAD guru and author Ellen Finkelstein to provide you with the very latest coverage of both AutoCAD 2012 and AutoCAD LT 2012. It begins with a Quick Start tutorial, so you start creating right away. From there, the book covers so much in-depth material on AutoCAD that it is said that even Autodesk employees keep this comprehensive book at their desks. A DVD is included that features before-and-after drawings of all the tutorials and plenty of great examples from AutoCAD prof

  6. 7 CFR 15b.4 - Discrimination prohibited.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Discrimination prohibited. 15b.4 Section 15b.4... ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE General Provisions § 15b.4 Discrimination prohibited. (a... in, be denied the benefits of, or otherwise be subjected to discrimination under any program or...

  7. 15 CFR 8b.4 - Discrimination prohibited.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Discrimination prohibited. 8b.4 Section 8b.4 Commerce and Foreign Trade Office of the Secretary of Commerce PROHIBITION OF DISCRIMINATION... Provisions § 8b.4 Discrimination prohibited. (a) General. No qualified handicapped individual shall, on the...

  8. Clonal relatedness of enterotoxigenic Escherichia coli (ETEC) strains expressing LT and CS17 isolated from children with diarrhoea in La Paz, Bolivia.

    Science.gov (United States)

    Rodas, Claudia; Klena, John D; Nicklasson, Matilda; Iniguez, Volga; Sjöling, Asa

    2011-01-01

    Enterotoxigenic Escherichia coli (ETEC) is a major cause of traveller's and infantile diarrhoea in the developing world. ETEC produces two toxins, a heat-stable toxin (known as ST) and a heat-labile toxin (LT) and colonization factors that help the bacteria to attach to epithelial cells. In this study, we characterized a subset of ETEC clinical isolates recovered from Bolivian children under 5 years of age using a combination of multilocus sequence typing (MLST) analysis, virulence typing, serotyping and antimicrobial resistance test patterns in order to determine the genetic background of ETEC strains circulating in Bolivia. We found that strains expressing the heat-labile (LT) enterotoxin and colonization factor CS17 were common and belonged to several MLST sequence types but mainly to sequence type-423 and sequence type-443 (Achtman scheme). To further study the LT/CS17 strains we analysed the nucleotide sequence of the CS17 operon and compared the structure to LT/CS17 ETEC isolates from Bangladesh. Sequence analysis confirmed that all sequence type-423 strains from Bolivia had a single nucleotide polymorphism; SNP(bol) in the CS17 operon that was also found in some other MLST sequence types from Bolivia but not in strains recovered from Bangladeshi children. The dominant ETEC clone in Bolivia (sequence type-423/SNP(bol)) was found to persist over multiple years and was associated with severe diarrhoea but these strains were variable with respect to antimicrobial resistance patterns. The results showed that although the LT/CS17 phenotype is common among ETEC strains in Bolivia, multiple clones, as determined by unique MLST sequence types, populate this phenotype. Our data also appear to suggest that acquisition and loss of antimicrobial resistance in LT-expressing CS17 ETEC clones is more dynamic than acquisition or loss of virulence factors.

  9. Clonal Relatedness of Enterotoxigenic Escherichia coli (ETEC) Strains Expressing LT and CS17 Isolated from Children with Diarrhoea in La Paz, Bolivia

    Science.gov (United States)

    Rodas, Claudia; Klena, John D.; Nicklasson, Matilda; Iniguez, Volga; Sjöling, Åsa

    2011-01-01

    Background Enterotoxigenic Escherichia coli (ETEC) is a major cause of traveller's and infantile diarrhoea in the developing world. ETEC produces two toxins, a heat-stable toxin (known as ST) and a heat-labile toxin (LT) and colonization factors that help the bacteria to attach to epithelial cells. Methodology/Principal Findings In this study, we characterized a subset of ETEC clinical isolates recovered from Bolivian children under 5 years of age using a combination of multilocus sequence typing (MLST) analysis, virulence typing, serotyping and antimicrobial resistance test patterns in order to determine the genetic background of ETEC strains circulating in Bolivia. We found that strains expressing the heat-labile (LT) enterotoxin and colonization factor CS17 were common and belonged to several MLST sequence types but mainly to sequence type-423 and sequence type-443 (Achtman scheme). To further study the LT/CS17 strains we analysed the nucleotide sequence of the CS17 operon and compared the structure to LT/CS17 ETEC isolates from Bangladesh. Sequence analysis confirmed that all sequence type-423 strains from Bolivia had a single nucleotide polymorphism; SNPbol in the CS17 operon that was also found in some other MLST sequence types from Bolivia but not in strains recovered from Bangladeshi children. The dominant ETEC clone in Bolivia (sequence type-423/SNPbol) was found to persist over multiple years and was associated with severe diarrhoea but these strains were variable with respect to antimicrobial resistance patterns. Conclusion/Significance The results showed that although the LT/CS17 phenotype is common among ETEC strains in Bolivia, multiple clones, as determined by unique MLST sequence types, populate this phenotype. Our data also appear to suggest that acquisition and loss of antimicrobial resistance in LT-expressing CS17 ETEC clones is more dynamic than acquisition or loss of virulence factors. PMID:22140423

  10. Bacillus sp. LT3 improves the survival of gnotobiotic brine shrimp (Artemia franciscana) larvae challenged with Vibrio campbellii by enhancing the innate immune response and by decreasing the activity of shrimp-associated vibrios.

    Science.gov (United States)

    Niu, Yufeng; Defoirdt, Tom; Baruah, Kartik; Van de Wiele, Tom; Dong, Shuanglin; Bossier, Peter

    2014-10-10

    Bacteria belonging to the genus Bacillus are amongst the most intensively studied group of bacteria for use as probiotics in aquaculture. However, the exact mechanism of action of these bacteria is often not well described, and the microbiota that are naturally present in cultures of test organisms often compromise the interpretation of the results. The present study aimed to evaluate the putative probiotic effect of Bacillus sp. LT3 in a model system with gnotobiotic brine shrimp Artemia franciscana larvae. The strain significantly increased the survival of brine shrimp larvae challenged with Vibrio campbellii when administered 6h before the challenge. Under these conditions, LT3 was able to colonize the brine shrimp gastrointestinal tract and to decrease the in vivo pathogen activity as indicated by the bioluminescence of the V. campbellii associated with brine shrimp larvae. In order to investigate the effect of the Bacillus strain on the innate immune system of the brine shrimp larvae, prophenoloxidase and transglutaminase mRNA levels were monitored, while heat shock protein 70 mRNA levels were measured as an indicator of physiological stress. Interestingly, 12h after challenge, the prophenoloxidase mRNA level in the larvae pre-treated with LT3 and challenged with V. campbellii was approximately 8-fold higher than in the other treatments. Further, a decreased mRNA level of transglutaminase gene and heat shock protein 70 gene suggested that pretreatment with LT3 results in less stress and tissue damage in the brine shrimp larvae upon V. campbellii challenge. These results indicated that Bacillus sp. LT3 could improve the survival of brine shrimp larvae when challenged with pathogenic V. campbellii, both by decreasing the in vivo activity of the pathogen and by priming the innate immune response through activating the prophenoloxidase system. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Synthesis and structure determination of new open-framework chromium carboxylate MIL-105 or CrIII(OH).{O2C-C6(CH3)4-CO2}.nH2O

    International Nuclear Information System (INIS)

    Serre, Christian; Millange, Franck; Devic, Thomas; Audebrand, Nathalie; Van Beek, Wouter

    2006-01-01

    Two new three-dimensional chromium(III) dicarboxylate, MIL-105 or Cr III (OH).{O 2 C-C 6 (CH 3 ) 4 -CO 2 }.nH 2 O, have been obtained under hydrothermal conditions, and their structures solved using X-ray powder diffraction data. Both solids are structural analogs of the known Cr benzenedicarboxylate compound (MIL-53). Both contain trans corner-sharing CrO 4 (OH) 2 octahedral chains connected by tetramethylterephthalate di-anions. Each chain is linked by the ligands to four other chains to form a three-dimensional framework with an array of 1D pores channels. The pores of the high temperature form of the solid, MIL-105ht, are empty. However, MIL-105ht re-hydrates at room temperature to finally give MIL-105lt with pores channels filled with free water molecules (lt: low temperature form; ht: high temperature form). The thermal behaviour of the two solids has been investigated using TGA. Crystal data for MIL-105ht: monoclinic space group C2/c with a = 19.653(1) A, b = 9.984(1) A, c = 6.970(1) A, β = 110.67(1) o and Z = 4. Crystal data for MIL-105lt: orthorhombic space group Pnam with a = 17.892(1) A, b = 11.165(1) A, c = 6.916(1) A and Z = 4

  12. Genetic fusions of a CFA/I/II/IV MEFA (multiepitope fusion antigen) and a toxoid fusion of heat-stable toxin (STa) and heat-labile toxin (LT) of enterotoxigenic Escherichia coli (ETEC) retain broad anti-CFA and antitoxin antigenicity.

    Science.gov (United States)

    Ruan, Xiaosai; Sack, David A; Zhang, Weiping

    2015-01-01

    Immunological heterogeneity has long been the major challenge in developing broadly effective vaccines to protect humans and animals against bacterial and viral infections. Enterotoxigenic Escherichia coli (ETEC) strains, the leading bacterial cause of diarrhea in humans, express at least 23 immunologically different colonization factor antigens (CFAs) and two distinct enterotoxins [heat-labile toxin (LT) and heat-stable toxin type Ib (STa or hSTa)]. ETEC strains expressing any one or two CFAs and either toxin cause diarrhea, therefore vaccines inducing broad immunity against a majority of CFAs, if not all, and both toxins are expected to be effective against ETEC. In this study, we applied the multiepitope fusion antigen (MEFA) strategy to construct ETEC antigens and examined antigens for broad anti-CFA and antitoxin immunogenicity. CFA MEFA CFA/I/II/IV [CVI 2014, 21(2):243-9], which carried epitopes of seven CFAs [CFA/I, CFA/II (CS1, CS2, CS3), CFA/IV (CS4, CS5, CS6)] expressed by the most prevalent and virulent ETEC strains, was genetically fused to LT-STa toxoid fusion monomer 3xSTaA14Q-dmLT or 3xSTaN12S-dmLT [IAI 2014, 82(5):1823-32] for CFA/I/II/IV-STaA14Q-dmLT and CFA/I/II/IV-STaN12S-dmLT MEFAs. Mice intraperitoneally immunized with either CFA/I/II/IV-STa-toxoid-dmLT MEFA developed antibodies specific to seven CFAs and both toxins, at levels equivalent or comparable to those induced from co-administration of the CFA/I/II/IV MEFA and toxoid fusion 3xSTaN12S-dmLT. Moreover, induced antibodies showed in vitro adherence inhibition activities against ETEC or E. coli strains expressing these seven CFAs and neutralization activities against both toxins. These results indicated CFA/I/II/IV-STa-toxoid-dmLT MEFA or CFA/I/II/IV MEFA combined with 3xSTaN12S-dmLT induced broadly protective anti-CFA and antitoxin immunity, and suggested their potential application in broadly effective ETEC vaccine development. This MEFA strategy may be generally used in multivalent

  13. Genetic fusions of a CFA/I/II/IV MEFA (multiepitope fusion antigen and a toxoid fusion of heat-stable toxin (STa and heat-labile toxin (LT of enterotoxigenic Escherichia coli (ETEC retain broad anti-CFA and antitoxin antigenicity.

    Directory of Open Access Journals (Sweden)

    Xiaosai Ruan

    Full Text Available Immunological heterogeneity has long been the major challenge in developing broadly effective vaccines to protect humans and animals against bacterial and viral infections. Enterotoxigenic Escherichia coli (ETEC strains, the leading bacterial cause of diarrhea in humans, express at least 23 immunologically different colonization factor antigens (CFAs and two distinct enterotoxins [heat-labile toxin (LT and heat-stable toxin type Ib (STa or hSTa]. ETEC strains expressing any one or two CFAs and either toxin cause diarrhea, therefore vaccines inducing broad immunity against a majority of CFAs, if not all, and both toxins are expected to be effective against ETEC. In this study, we applied the multiepitope fusion antigen (MEFA strategy to construct ETEC antigens and examined antigens for broad anti-CFA and antitoxin immunogenicity. CFA MEFA CFA/I/II/IV [CVI 2014, 21(2:243-9], which carried epitopes of seven CFAs [CFA/I, CFA/II (CS1, CS2, CS3, CFA/IV (CS4, CS5, CS6] expressed by the most prevalent and virulent ETEC strains, was genetically fused to LT-STa toxoid fusion monomer 3xSTaA14Q-dmLT or 3xSTaN12S-dmLT [IAI 2014, 82(5:1823-32] for CFA/I/II/IV-STaA14Q-dmLT and CFA/I/II/IV-STaN12S-dmLT MEFAs. Mice intraperitoneally immunized with either CFA/I/II/IV-STa-toxoid-dmLT MEFA developed antibodies specific to seven CFAs and both toxins, at levels equivalent or comparable to those induced from co-administration of the CFA/I/II/IV MEFA and toxoid fusion 3xSTaN12S-dmLT. Moreover, induced antibodies showed in vitro adherence inhibition activities against ETEC or E. coli strains expressing these seven CFAs and neutralization activities against both toxins. These results indicated CFA/I/II/IV-STa-toxoid-dmLT MEFA or CFA/I/II/IV MEFA combined with 3xSTaN12S-dmLT induced broadly protective anti-CFA and antitoxin immunity, and suggested their potential application in broadly effective ETEC vaccine development. This MEFA strategy may be generally used in

  14. CAREN-4, ENDF/B Utility, Discontinuity Check at Resonance Region Boundary. CHECK-4, ENDF/B Utility, Structure Consistency Check and Format Check. CRECT, ENDF/B Utility, Data Correlation and Data Update. DICT-4, ENDF/B Utility, Section Table of Contents Generator. LISTF-4, ENDF/B Utility, Data Listing. RIGEL-4, ENDF/B Utility, Data Retrieval, BCD to BIN Conversion. SUMUP-4, ENDF/B Utility, Partial Cross-Sections Sum Check Against Tot Cross-Sections

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1975-08-01

    Description of problem or function: These programs are updated versions of ENDF/B checking, retrieval, and display codes capable of processing the Version-IV data files. RIGEL4 retrieves ENDF/B data and changes mode (BCD-BIN) or arrangement. Updated version processes decay data (mf=1, mt=457) and error files. CHECK4 checks the structure, consistency, and formats of ENDF data files. Updated version recognizes newly defined mt and mf numbers, checks mt=457 and the formats of the error files, contains RSIC photon file changes. SUMUP4 checks whether partial cross sections add up to the total. Updated version flags grid points present in the partial cross section, absent in the total. LISTF4 produces interpreted listings of ENDF/B data. Updated version lists mt=457, skips over error files, contains minor corrections. PLOTF4 produces plots of ENDF/B data. Updated version plots mt=457, skips over error files, contains minor corrections. RESEND processes ENDF materials with resonance parameters into a pointwise form. Capability of processing Adler-Adler parameters added. CRECT corrects ENDF/B data files. DICT4 generates a section table of contents (dictionary) for ENDF/B materials. CAREN4 tests for discontinuities across the limits of resonance ranges of an ENDF/B material. Updated version contains minor corrections.

  15. Flavonoids such as luteolin, fisetin and apigenin are inhibitors of interleukin-4 and interleukin-13 production by activated human basophils.

    Science.gov (United States)

    Hirano, Toru; Higa, Shinji; Arimitsu, Junsuke; Naka, Tetsuji; Shima, Yoshihito; Ohshima, Shiro; Fujimoto, Minoru; Yamadori, Tomoki; Kawase, Ichiro; Tanaka, Toshio

    2004-06-01

    We have previously shown that fisetin, a flavonol, inhibits IL-4 and IL-13 synthesis by allergen- or anti-IgE-antibody-stimulated basophils. This time, we investigated the inhibition of IL-4 and IL-13 production by basophils by other flavonoids and attempted to determine the fundamental structure of flavonoids related to inhibition. We additionally investigated whether flavonoids suppress leukotriene C4 synthesis by basophils and IL-4 synthesis by T cells in response to anti-CD3 antibody. Highly purified peripheral basophils were stimulated for 12 h with anti-IgE antibody alone or anti-IgE antibody plus IL-3 in the presence of various concentrations of 18 different kinds of flavones and flavonols. IL-4 and IL-13 concentrations in the supernatants were then measured. Leukotriene C4 synthesis was also measured after basophils were stimulated for 1 h in the presence of flavonoids. Regarding the inhibitory activity of flavonoids on IL-4 synthesis by T cells, peripheral blood mononuclear cells were cultured with flavonoids in anti-CD3-antibody-bound plates for 2 days. Luteolin, fisetin and apigenin were found to be the strongest inhibitors of both IL-4 and IL-13 production by basophils but did not affect leukotriene C4 synthesis. At higher concentrations, these flavonoids suppressed IL-4 production by T cells. Based on a hierarchy of inhibitory activity, the basic structure for IL-4 inhibition by basophils was determined. Due to the inhibitory activity of flavonoids on IL-4 and IL-13 synthesis, it can be expected that the intake of flavonoids, depending on the quantity and quality, may ameliorate allergic symptoms or prevent the onset of allergic diseases. Copyright 2004 S. Karger AG, Basel

  16. Numerical modelling of the processes in the WWER-1000 containment building during cold leg LOCA using the CONTEMPT-LT/026 code

    International Nuclear Information System (INIS)

    Kolev, N.I.; Sybotinov, L.S.

    1984-01-01

    The CONTEMPT-LT/026 code has been used to produce numerical results for the processes in a WWER-1000 containment building during cold leg LOCA with break at the reactor vessel. The objective of the analysis is to estimate the maximal loads on the containment in case of LOCA. Available design data for the geometry and for the operational characteristics of the low-pressure ECC system and the sprinkler system have been used. Boundary conditions such as mass flow and enthalpies at the breach are given by a RELAP4/MOD6 computation. Hydrogen explosions in the containment are not considered. It is found that in case of normal functioning of the low-pressure ECC system the maximal pressure is 3,26±0,44 bar. In the case of malfunctioning of the low-pressure ECC system, the predicted maximal pressure is 4±0,44 bar, when: a) only 50% of the heat transfer surface of the heat exchanger is effectively used due to pollution; b) the main pipeline of the sprinkler is broken; c) the pipeline to the heat exchanger is partially broken so that the mass flow through the exchanger is only 50% of the nominal; and d) ECC low-pressure ECC system attains its maximal efficiency within 3 min, the predicted maximal pressure is 4±0,44 bar

  17. Sensitization rates of airborne pollen and mold in children

    Directory of Open Access Journals (Sweden)

    So Hyun Park

    2012-09-01

    Full Text Available &lt;B&gt;Purpose:&lt;/b&gt; Aeroallergens are important causative factors of allergic diseases. Previous studies on aeroallergen sensitization rates investigated patients groups that had visited pediatric allergy clinics. In contrast, we investigated sensitization rates in a general population group of elementary school to teenage students in Incheon, Jeju, and Ulsan. &lt;b&gt;Methods:&lt;/B&gt; After obtaining parental consent, skin-prick tests were performed on 5,094 students between March and June 2010. Elementary school students were tested for 18 common aeroallergens, whereas middle and high school students were tested for 25 allergens. The 25 allergens included &lt;I&gt;Dermatophagoides pteronyssinus, Dermatophagoides farinae&lt;/I&gt;, pollen (birch, alder, oak, Japanese cedar, pine, willow, elm, maple, Bermuda grass, timothy grass, rye grass, orchard grass, meadow grass, vernal grass, mugwort, Japanese hop, fat hen, ragweed, and plantain, and mold (&lt;I&gt;Penicillatum, Aspergillus, Cladosporium, and Alternaria&lt;/I&gt;. &lt;b&gt;Results:&lt;/b&gt; The sensitization rates in descending order were 25.79% (&lt;I&gt;D. pteronyssinus&lt;/I&gt; , 18.66% (&lt;I&gt;D. farinae&lt;/I&gt; , 6.20% (mugwort, and 4.07% (willow in Incheon; 33.35% (&lt;I&gt;D. pteronyssinus&lt;/I&gt; , 24.78% (&lt;I&gt;D. farinae&lt;/I&gt;, 15.36% (Japanese cedar, and 7.33% (Alternaria in Jeju; and 32.79% (D. pteronyssinus, 30.27% (D. farinae, 10.13% (alder, and 8.68% (birch in Ulsan. The dust mite allergen showed the highest sensitization rate among the 3 regions. The sensitization rate of tree pollen was the highest in Ulsan, whereas that of Alternaria was the highest in Jeju. The ragweed sensitization rates were 0.99% in Incheon, 1.07% in Jeju, and 0.81% in Ulsan. &lt;b&gt;Conclusion:&lt;/b&gt; The

  18. Impaired neonatal macrophage phagocytosis is not explained by overproduction of prostaglandin E2

    Directory of Open Access Journals (Sweden)

    Ballinger Megan N

    2011-12-01

    Full Text Available Abstract Background Neonates and young infants manifest increased susceptibility to bacterial, viral and fungal lung infections. Previous work has identified a role for eicosanoids in mediating host defense functions of macrophages. This study examines the relationship between alveolar macrophage (AM host defense and production of lipid mediators during the neonatal period compared to adult AMs. Methods AMs were harvested from young (day 7 and day 14 and adult (~10 week rats. The functionality of these cells was assessed by examining their ability to phagocytose opsonized targets, produce cytokines, eicosanoids and intracellular cAMP measured by enzyme immunoassays, and gene expression of proteins, enzymes and receptors essential for eicosanoid generation and phagocytosis measured by real time RT-PCR. Results AMs from young animals (day 7 and 14 were defective in their ability to phagocytose opsonized targets and produce tumor necrosis factor (TNF- α. In addition, young AMs produce more prostaglandin (PG E2, a suppressor of host defense, and less leukotriene (LT B4, a promoter of host defense. Young AMs express higher levels of enzymes responsible for the production of PGE2 and LTB4; however, there was no change in the expression of E prostanoid (EP receptors or LT receptors. Despite the similar EP profiles, young AMs are more responsive to PGE2 as evidenced by their increased production of the important second messenger, cyclic AMP. In addition, young AMs express higher levels of PDE3B and lower levels of PDE4C compared to adult AMs. However, even though the young AMs produced a skewed eicosanoid profile, neither the inhibition of PGE2 by aspirin nor the addition of exogenous LTB4 rescued the defective opsonized phagocytosis. Examination of a receptor responsible for mediating opsonized phagocytosis showed a significant decrease in the gene expression levels of the Fcgamma receptor in young (day 7 AMs compared to adult AMs. Conclusion These

  19. Double symmetry breaking in TmFe{sub 4}Ge{sub 2} compared to RFe{sub 4}Ge{sub 2} (R=Y, Lu, Er, Ho, Dy) magnetic behaviour

    Energy Technology Data Exchange (ETDEWEB)

    Schobinger-Papamantellos, P., E-mail: Schobinger@mat.ethz.ch [Laboratory of Crystallography, ETH-Zürich, 8093 Zürich (Switzerland); Buschow, K.H.J. [Van der Waals-Zeeman Institute, University of Amsterdam, NL-1018 XE (Netherlands); Rodríguez-Carvajal, J. [Institut Laue-Langevin, 156X, 38042 Grenoble Cédex (France)

    2014-04-15

    TmFe4Ge{sub 2} undergoes a double magneto-elastic first order transition at T{sub N},T{sub c} where the high temperature (HT) tetragonal phase disproportionate into two distinct orthorhombic low temperature (LT) phases with commensurate and incommensurate magnetic wave vectors respectively: P4{sub 2}/mnm(HT)T{sub N},T{sub c}→Cmmmq{sub 1}=(0,1/2 ,0)+Pnnm(q{sub 2}=(0,q{sub y},0),q{sub y}≈2/11(LT) Neutron diffraction shows the relative portions of the LT Cmmm and Pnnm competing phases change linearly with T. The amount of the majority HT phase Pnnm (54% at 30 K) decreases linearly to 30% down to 10 K in favour of the Cmmm phase that dominates the range 26–1.5 K. The Tm moments point along the c-axis in both phases while the Fe moments have canted arrangements. The μ{sub Tm}=3.54(3) μ{sub B}/atom at 1.5 K is strongly reduced below the Tm{sup 3+} free ion value g{sub J}J=7 μ{sub B} for the q{sub 1} phase. The q{sub 2} phase corresponds to a 3D canted sinusoidal arrangement. The results are summarised on a phase diagram and compared to the findings in RFe{sub 4}Ge{sub 2} (R=Y, Lu, Er, Ho, Dy) that are reviewed. The multitude of transition paths occurring in those systems arise from the competing magnetoelastic mechanisms involving the R-crystal field anisotropy, the exchange interactions R–R, R–Fe, Fe–Fe of the two sublattices and their coupling to the lattice strain. The geometrical frustration emerging from the compact tetrahedral Fe arrangement with antiferromagnetic interactions leads to 2D and 3D canted, incommensurate and non-magnetic states. The Cmmm transition is triggered by dominating R–R and R–Fe interactions becoming stronger at LT while the Pnnm phase is promoted by Fe–Fe and R–Fe interactions that prevail at HT. Included is also the magnetic structure of the ferromagnetic impurity phase Fe{sub 3}Ge. - Highlights: • Magnetic phase diagram of tetragonal TmFe{sub 4}Ge{sub 2} compound studied by neutron diffraction. • Unusual first

  20. 76 FR 19724 - Airworthiness Directives; Airbus Model A300 B4-600, B4-600R, and F4-600R Series Airplanes, and...

    Science.gov (United States)

    2011-04-08

    ... B4-600, B4-600R, and F4-600R Series Airplanes, and Model C4-605R Variant F Airplanes (Collectively... F4-605R and F4-622R airplanes, and Model A300 C4-605R Variant F airplanes; and Model A310-203, -204...

  1. 76 FR 47430 - Airworthiness Directives; Airbus Model A300 B4-600, A300 B4-600R, and A300 F4-600R Series...

    Science.gov (United States)

    2011-08-05

    ... Airworthiness Directives; Airbus Model A300 B4-600, A300 B4-600R, and A300 F4-600R Series Airplanes, and Model..., B4-622R, F4-605R, F4-622R, and C4-605R Variant F airplanes; and Model A310-203, -204, -221, -222...

  2. Role of LTB4 in the pathogenesis of elastase-induced murine pulmonary emphysema

    Science.gov (United States)

    Paige, Mikell; Hanna, Halim; Kim, Su H.; Burdick, Marie D.; Strieter, Robert M.

    2010-01-01

    Exaggerated levels of the leukotriene B4 (LTB4) frequently coexist at sites of inflammation and tissue remodeling. Therefore, we hypothesize that the LTB4 pathway plays an important role in the pathogenesis of neutrophilic inflammation that contributes to pulmonary emphysema. In this study, significant levels of LTB4 were detected in human lung tissues with emphysema compared with lungs without emphysema (9,497 ± 2,839 vs. 4,142 ± 1,173 pg/ml, n = 9 vs. 10, P = 0.04). To further determine the biological role of LTB4 in the pathogenesis of emphysema, we compared the lungs of wild-type (WT) and LTA4 hydrolase−/− mice (LTB4 deficient, LTA4H−/−) exposed to intranasal elastase or vehicle control. We found that intranasal elastase induced accumulation of LTB4 in the lungs and caused progressively worsening emphysema between 14 and 28 days after elastase exposure in WT mice but not in LTA4H−/− mice. Premortem physiology documented increased lung compliance in elastase-exposed WT mice compared with elastase-exposed LTA4H−/− mice as measured by Flexivent (0.058 ± 0.005 vs. 0.041 ± 0.002 ml/cmH2O pressure). Postmortem morphometry documented increased total lung volume and alveolar sizes in elastase-exposed WT mice compared with elastase-exposed LTA4H−/− mice as measured by volume displacement and alveolar chord length assessment. Furthermore, elastase-exposed LTA4H−/− mice were found to have significantly delayed influx of the CD45highCD11bhighLy6Ghigh leukocytes compatible with neutrophils compared with elastase-exposed WT mice. Mechanistic insights to these phenotypes were provided by demonstrating protection from elastase-induced murine emphysema with neutrophil depletion in the elastase-exposed WT mice and by demonstrating time-dependent modulation of cysteinyl leukotriene biosynthesis in the elastase-exposed LTA4H−/− mice compared with elastase-exposed WT mice. Together, these findings demonstrated that LTB4 played an important role in

  3. 26 CFR 1.167(b)-4 - Other methods.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Other methods. 1.167(b)-4 Section 1.167(b)-4...) INCOME TAXES (CONTINUED) Itemized Deductions for Individuals and Corporations § 1.167(b)-4 Other methods. (a) Under section 167(b)(4) a taxpayer may use any consistent method of computing depreciation, such...

  4. 76 FR 25259 - Airworthiness Directives; Airbus Model A300 B4-600, A300 B4-600R, and A300 F4-600R Series...

    Science.gov (United States)

    2011-05-04

    ... Airworthiness Directives; Airbus Model A300 B4-600, A300 B4-600R, and A300 F4-600R Series Airplanes, and Model...-605R, B4-622R, F4-605R, F4-622R, and C4-605R Variant F airplanes; and Model A310-203, -204, -221, -222...

  5. 26 CFR 1.50B-4 - Partnerships.

    Science.gov (United States)

    2010-04-01

    ... § 1.50A-3, or if the partnership fails to pay comparable wages and such failure is subject to the... 26 Internal Revenue 1 2010-04-01 2010-04-01 true Partnerships. 1.50B-4 Section 1.50B-4 Internal... Credit for Expenses of Work Incentive Programs § 1.50B-4 Partnerships. (a) General rule—(1) In general...

  6. Interface interaction in the B{sub 4}C/(Fe-B-C) system

    Energy Technology Data Exchange (ETDEWEB)

    Aizenshtein, M. [Department of Material Engineering, Ben-Gurion University, P.O. Box 653, Beer-Sheva 84105 (Israel); NRC-Negev, P.O. Box 9001, Beer-Sheva 84190 (Israel); Mizrahi, I.; Froumin, N.; Hayun, S.; Dariel, M.P. [Department of Material Engineering, Ben-Gurion University, P.O. Box 653, Beer-Sheva 84105 (Israel); Frage, N. [Department of Material Engineering, Ben-Gurion University, P.O. Box 653, Beer-Sheva 84105 (Israel)], E-mail: nfrage@bgu.ac.il

    2008-11-15

    The wetting behavior in the B{sub 4}C/(Fe-C-B) system was investigated in order to clarify the role of Fe additions on the sinterability of B{sub 4}C. Iron and its alloys with C and B react with the boron carbide substrate and form a reaction zone consisting of a fine mixture of FeB and graphite. The apparent contact angles are relatively low for the alloys with a moderate concentration of the boron and carbon and allow liquid phase sintering to occur in the B{sub 4}C-Fe mixtures. A dilatometric study of the sintering kinetics confirms that liquid phase sintering actually takes place and leads to improved mass transfer. A thermodynamic analysis of the ternary Fe-B-C system allows accounting for the experimental observations.

  7. Population-based open-label clinical effectiveness assessment of the cysteinyl leukotriene receptor antagonist pranlukast

    Directory of Open Access Journals (Sweden)

    Gen Tamura

    2000-01-01

    Full Text Available Although the efficacy of cysteinyl leukotriene receptor antagonists in asthma therapy has been established through controlled clinical trials, there are no data concerning the effectiveness of their use in clinical practice, in which there is no rigid selection based on specific inclusion and exclusion criteria. The aim of the present study was to evaluate the effectiveness of pranlukast in clinical practice. More than 2500 outpatients with mild to severe persistent asthma answered an input questionnaire, which consisted of 33 items assessing asthma symptoms in terms of six activities of daily living during the previous 2 weeks. Of these patients, 1138 received treatment with pranlukast and answered the same questionnaire 4–6 weeks after the start of treatment. In 923 of these 1138 patients, we examined the impact of concomitantly used inhaled steroids, β2-adrenergic agonists or sustained-release theophylline on the effectiveness of pranlukast treatment. One hundred and sixty-seven control patients completed the questionnaire twice but did not receive pranlukast treatment. We found a significant decrease in the number of asthma symptoms reported among both the 1138 patients treated with pranlukast and the 167 control patients. However, the magnitude of the decrease in symptoms was significantly (P < 0.001 greater with pranlukast treatment. Moreover, pranlukast was equally efficacious in the presence and absence of concomitantly used inhaled steroids, β2-adrenergic agonists or sustained-release theophylline. In conclusion, pranlukast was shown to have clinical effectiveness in the treatment of mild to severe persistent asthma symptoms.

  8. Formalin-inactivated EV71 vaccine candidate induced cross-neutralizing antibody against subgenotypes B1, B4, B5 and C4A in adult volunteers.

    Directory of Open Access Journals (Sweden)

    Ai-Hsiang Chou

    Full Text Available Enterovirus 71 (EV71 has caused several epidemics of hand, foot and mouth diseases (HFMD in Asia. No effective EV71 vaccine is available. A randomized and open-label phase I clinical study registered with ClinicalTrials.gov #NCT01268787, aims to evaluate the safety, reactogenicity and immunogenicity of a formalin-inactivated EV71 vaccine candidate (EV71vac at 5- and 10-µg doses. In this study we report the cross-neutralizing antibody responses from each volunteer against different subgenotypes of EV71 and CVA16.Sixty eligible healthy adults were recruited and vaccinated. Blood samples were obtained on day 0, 21 and 42 and tested against B1, B4, B5, C2, C4A, C4B and CVA16 for cross-neutralizing antibody responses.The immunogenicity of both 5- and 10- µg doses were found to be very similar. Approximately 45% of the participants had 4-fold increase in Nt, but there was no further increase in Nt after the second dose. EV71vac induced very strong cross-neutralizing antibody responses in >85% of volunteers without pre-existing Nt against subgenotype B1, B5 and C4A. EV71vac elicited weak cross-neutralizing antibody responses (∼20% of participants against a C4B and Coxsackie virus A16. Over 90% of vaccinated volunteers did not develop cross-neutralizing antibody responses (Nt<8 against a C2 strain. EV71vac can boost and significantly enhance the neutralizing antibody responses in volunteers who already had pre-vaccination antibodies against EV71 and/or CVA16.EV71vac is efficient in eliciting cross-neutralizing antibody responses against EV71 subgenotypes B1, B4, B5, and C4A, and provides the rationale for its evaluation in phase II clinical trials.ClinicalTrials.gov NCT01268787.

  9. 45 CFR 73b.4 - Proceedings.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Proceedings. 73b.4 Section 73b.4 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION DEBARMENT OR SUSPENSION OF FORMER EMPLOYEES... reasonable cause to believe that a former officer or employee, including a former special Government employee...

  10. Airpower Leadership on the Front Line: Lt Gen George H. Brett and Combat Command

    Science.gov (United States)

    2006-09-01

    was assigned the additional duty of unit photographer and historian, bequeathing a photo album depicting his adventures to his oldest daughter.10 Lt...his fellow residents with piano music when the men were off duty.21 At the close of the war Brett was a temporary major and listed among officers who

  11. Pressure effect on structural, elastic, and thermodynamic properties of tetragonal B4C4

    Directory of Open Access Journals (Sweden)

    Baobing Zheng

    2015-03-01

    Full Text Available The compressibility, elastic anisotropy, and thermodynamic properties of the recently proposed tetragonal B4C4 (t-B4C4 are investigated under high temperature and high pressure by using of first-principles calculations method. The elastic constants, bulk modulus, shear modulus, Young’s modulus, Vickers hardness, Pugh’s modulus ratio, and Poisson’s ratio for t-B4C4 under various pressures are systematically explored, the obtained results indicate that t-B4C4 is a stiffer material. The elastic anisotropies of t-B4C4 are discussed in detail under pressure from 0 GPa to 100 GPa. The thermodynamic properties of t-B4C4, such as Debye temperature, heat capacity, and thermal expansion coefficient are investigated by the quasi-harmonic Debye model.

  12. EphB4 as a therapeutic target in mesothelioma

    International Nuclear Information System (INIS)

    Liu, Ren; Ferguson, Benjamin D; Zhou, Yue; Naga, Kranthi; Salgia, Ravi; Gill, Parkash S; Krasnoperov, Valery

    2013-01-01

    Malignant pleural mesothelioma (MPM) often develops decades following exposure to asbestos. Current best therapy produces a response in only half of patients, and the median survival with this therapy remains under a year. A search for novel targets and therapeutics is underway, and recently identified targets include VEGF, Notch, and EphB4-Ephrin-B2. Each of these targets has dual activity, promoting tumor cell growth as well as tumor angiogenesis. We investigated EphB4 expression in 39 human mesothelioma tissues by immunohistochemistry. Xenograft tumors established with human mesothelioma cells were treated with an EphB4 inhibitor (monomeric soluble EphB4 fused to human serum albumin, or sEphB4-HSA). The combinatorial effect of sEphB4-HSA and biologic agent was also studied. EphB4 was overexpressed in 72% of mesothelioma tissues evaluated, with 85% of epithelioid and 38% of sarcomatoid subtypes demonstrating overexpression. The EphB4 inhibitor sEphB4-HSA was highly active as a single agent to inhibit tumor growth, accompanied by tumor cell apoptosis and inhibition of PI3K and Src signaling. Combination of sEphB4-HSA and the anti-VEGF antibody (Bevacizumab) was superior to each agent alone and led to complete tumor regression. EphB4 is a potential therapeutic target in mesothelioma. Clinical investigation of sEphB4-HSA as a single agent and in combination with VEGF inhibitors is warranted

  13. Susceptibility to endotoxin induced uveitis is not reduced in mice deficient in BLT1, the high affinity leukotriene B4 receptor

    OpenAIRE

    Smith, J R; Subbarao, K; Franc, D T; Haribabu, B; Rosenbaum, J T

    2004-01-01

    Aim: To investigate the role of arachidonic acid derived chemotactic factor, LTB4, in the development of endotoxin induced uveitis (EIU), using mice deficient in the BLT1 gene which encodes the high affinity LTB4 receptor.

  14. Inhibition of common cold-induced aggravation of childhood asthma by leukotriene receptor antagonists.

    Science.gov (United States)

    Yoshihara, Shigemi; Fukuda, Hironobu; Abe, Toshio; Nishida, Mitsuhiro; Yamada, Yumi; Kanno, Noriko; Arisaka, Osamu

    2012-09-01

    Virus infection is an important risk factor for aggravation of childhood asthma. The objective of this study was to examine the effect of drugs on aggravation of asthma induced by a common cold. Asthma control was examined in a survey of 1,014 Japanese pediatric patients with bronchial asthma. The occurrence of common cold, asthma control, and drugs used for asthma control were investigated using a modified Childhood Asthma Control Test (C-ACT) for patients aged cold and aggravation of asthma were significantly higher in patients aged cold-induced aggravation was significantly less effective in patients aged cold, asthma control was significantly more effective for those treated with leukotriene receptor antagonists (LTRAs) compared to treatment without LTRAs. Asthma control did not differ between patients who did or did not take inhaled corticosteroids or long-acting β2 stimulants. These findings showed a high prevalence of common cold in younger patients with childhood asthma and indicated that common cold can induce aggravation of asthma. LTRAs are useful for long-term asthma control in very young patients who develop an asthma attack due to a common cold.

  15. Homotopy perturbation method with Laplace Transform (LT-HPM) for solving Lane-Emden type differential equations (LETDEs).

    Science.gov (United States)

    Tripathi, Rajnee; Mishra, Hradyesh Kumar

    2016-01-01

    In this communication, we describe the Homotopy Perturbation Method with Laplace Transform (LT-HPM), which is used to solve the Lane-Emden type differential equations. It's very difficult to solve numerically the Lane-Emden types of the differential equation. Here we implemented this method for two linear homogeneous, two linear nonhomogeneous, and four nonlinear homogeneous Lane-Emden type differential equations and use their appropriate comparisons with exact solutions. In the current study, some examples are better than other existing methods with their nearer results in the form of power series. The Laplace transform used to accelerate the convergence of power series and the results are shown in the tables and graphs which have good agreement with the other existing method in the literature. The results show that LT-HPM is very effective and easy to implement.

  16. 11B study of spin dynamics in Y/sub 1-x/RE/sub x/Rh4B4

    International Nuclear Information System (INIS)

    Kumagai, K.; Fradin, F.Y.

    1982-06-01

    There has been intense interest in re-entrance and coexistence in ternary rare earth magnetic superconductors of the form RE Rh 4 B 4 . Of particular interest in this investigation is the effect of the superconducting state on the RKKY (Yosida, 1957) coupling between RE ions. Since one expects the conduction electron spin susceptibility chi/sup e/(q) to be cut off for q - 1 for the RE moments in the superconducting state. This paper reports on the spin dynamics of the RE ions using the 11 B nuclear magnetic relaxation rate T 1- 1 in dilute Y/sub 1-x/RE/sub x/Rh 4 B 4 (RE = Gd and Er)

  17. Kefir Kültürünün Beyaz Peynir Yapımında Kullanılması Üzerine bir Araştırma

    Directory of Open Access Journals (Sweden)

    Hasan Yaygın

    2015-02-01

    Full Text Available Beyaz peynir yapımında kullanılacak saf kültürde yer alması gereken mikroorganizmaları saptamak amacı ile bazı çalışmalar yapılmıştır. Araştırıcıların çoğunluğu saf kültürde S. lactis, S. cremoris ve L. casei’ nin bulunması gerektiğini belirtmişlerdir. Bu çalışmada beyaz peynir yapımında saf kültür olarak kefir kültürü kullanılmıştır. Kefir kültüründe söz konusu bakterilerle beraber bazı maya ve bakteriler de bulunmaktadır. Araştırma sonuçları kefir kültürü katılan sütten yapılan beyaz peynirde asitlik gelişiminin istenilen düzeyde olduğu; tat ve aroma ile yapının tüketiciler tarafından beğenildiğini ortaya çıkarmıştır.

  18. Predictors of nonresponse to intravenous immunoglobulin therapy in Kawasaki disease

    Directory of Open Access Journals (Sweden)

    Hyo Min Park

    2013-02-01

    Full Text Available &lt;b&gt;Purpose:&lt;/b&gt; It has been reported that 10% to 20% of children with Kawasaki disease (KD will not respond to intravenous immunoglobulin (IVIG treatment. In this study, we aimed to identify useful predictors of therapeutic failure in children with KD. &lt;b&gt;Methods:&lt;/b&gt; We examined 309 children diagnosed with KD at the Kyungpook National University Hospital and the Inje University Busan Paik Hospital between January 2005 and June 2011. We retrospectively reviewed their medical records and analyzed multiple parameters in responders and nonresponders to IVIG. &lt;b&gt;Results:&lt;/b&gt; Among the 309 children, 30 (9.7% did not respond to IVIG. They had significantly higher proportion of neutrophils, and higher levels of aspartate aminotransferase, alanine aminotransferase (ALT, total bilirubin, and N-terminal fragment of B-type natriuretic peptide than did responders. IVIGnonresponders had a significantly longer duration of hospitalization, and more frequently experienced coronary artery lesion, and sterile pyuria. No differences in the duration of fever at initial treatment or, clinical features were noted. &lt;b&gt;Conclusion:&lt;/b&gt; Two independent predictors (ALT?#248;4 IU/L, total bilirubin?#240;.9 mg/dL for nonresponse were confirmed through multivariate logistic regression analysis. Thus elevated ALT and total bilirubin levels might be useful in predicting nonresponse to IVIG therapy in children with KD.

  19. ltürel Farklılıkların Yönetiminde İnsan Kaynakları Stratejilerinin Rolü : IKEA Örneği

    OpenAIRE

    Helvacıoğlu, Nuray; Özutku, Hatice

    2010-01-01

    Günümüzde işletmelerin küreselleşme eğilimleri, işgören çeşitliliğinin ve kültürel farklılıkların artmasına neden olmaktadır. İşletmelerin rekabet üstünlüğü elde edebilmeleri için kültürel farklılıkların etkin bir biçimde yönetilmesi gerekmektedir. Bu çalışmanın amacı, kültürel farklılıkların yönetiminde insan kaynakları yönetiminin rolünün belirlenmesidir. Bu kapsamda, kültürel farklılıkların yönetiminde ön plana çıkan İsveç kökeni IKEA firmasını konu alan nitel bir araş...

  20. Montelukast potentiates the anticonvulsant effect of phenobarbital in mice: an isobolographic analysis.

    Science.gov (United States)

    Fleck, Juliana; Marafiga, Joseane Righes; Jesse, Ana Cláudia; Ribeiro, Leandro Rodrigo; Rambo, Leonardo Magno; Mello, Carlos Fernando

    2015-04-01

    Although leukotrienes have been implicated in seizures, no study has systematically investigated whether the blockade of CysLT1 receptors synergistically increases the anticonvulsant action of classic antiepileptics. In this study, behavioral and electroencephalographic methods, as well as isobolographic analysis, are used to show that the CysLT1 inverse agonist montelukast synergistically increases the anticonvulsant action of phenobarbital against pentylenetetrazole-induced seizures. Moreover, it is shown that LTD4 reverses the effect of montelukast. The experimentally derived ED50mix value for a fixed-ratio combination (1:1 proportion) of montelukast plus phenobarbital was 0.06±0.02 μmol, whereas the additively calculated ED50add value was 0.49±0.03 μmol. The calculated interaction index was 0.12, indicating a synergistic interaction. The association of montelukast significantly decreased the antiseizure ED50 for phenobarbital (0.74 and 0.04 μmol in the absence and presence of montelukast, respectively) and, consequently, phenobarbital-induced sedation at equieffective doses. The demonstration of a strong synergism between montelukast and phenobarbital is particularly relevant because both drugs are already used in the clinics, foreseeing an immediate translational application for epileptic patients who have drug-resistant seizures. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Structural changes of Bi sub 1. 8 Sr sub 2 (Ca sub 1 minus x Y sub x )Cu sub 2. 2 O sub z ceramics with yttrium content studied by electron diffraction and high-resolution electron microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Onozuka, T.; Iwabuchi, Y.; Fukase, T. (Institute for Materials Research, Tohoku University, Sendai 980, Japan (JP)); Sato, H. (School of Materials Engineering, Purdue University, West Lafayette, Indiana 47907 (USA)); Mitchell, T.E. (Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (USA))

    1991-06-01

    The mode of the incommensurate modulation in the {ital b} direction of the Bi{sub 1.8}Sr{sub 2}(Ca{sub 1{minus}{ital x}}Y{sub {ital x}})Cu{sub 2.2}O{sub {ital z}} (0.05{lt}{ital x}{lt}0.75) system is investigated by means of electron diffraction and high-resolution lattice imaging. The change of period of the long-period structure with {ital x} is found to be basically due to the mixing ratio of domains of two modulation periods with {ital b}=4.5{ital b}{sub 0} and 5{ital b}{sub 0} or 4.5{ital b}{sub 0} and 4{ital b}{sub 0}, thus creating periods of {ital b}=4.75{ital b}{sub 0--}4.0{ital b}{sub 0}. The fundamental orthorhombic lattice has dimensions of {ital a}{congruent}{ital b}{congruent}{ital b}{sub 0} (0.54 nm) and {ital c}{congruent}{ital c}{sub 0} (3.1 nm). The change of the mixing mode from one to the other mentioned above occurs just in the yttrium concentration range, 0.45{lt}{ital x}{lt}0.65, which also corresponds to the superconductor (metallic)-to-semiconductor transition boundary. The mixing modes of the domains are directly recorded as a contrast modulation with half periods, 4.5{ital b}{sub 0}/2 and 5{ital b}{sub 0}/2 or 4.5{ital b}{sub 0}/2 and 4{ital b}{sub 0}/2 in high-resolution lattice images. These images are reproduced well by a multislice computer-simulation technique.

  2. Excellent outcome of immunomodulation or Bruton’s tyrosine kinase inhibition in highly refractory primary cutaneous diffuse large B-cell lymphoma, leg type

    Directory of Open Access Journals (Sweden)

    Eva Gupta

    2015-12-01

    Full Text Available Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT is a rare diffuse large B-cell lymphoma confined to the skin of the legs. The typical presentation is characterized by solitary or multiple growing plaques, usually confined to one leg. We report a case of PCDLBCL-LT of activated B-cell subtype characterized by multiple local relapses in the legs, initially, and systemic relapses about seven years after the diagnosis. Local relapses were sensitive to radiation therapy. Cutaneous and systemic relapses responded well to immunomodulatory therapy with lenalidomide followed by Bruton’s tyrosine kinase inhibition with ibrutinib. Ibrutinib is the only treatment that resulted in long-lasting complete remission. Lenalidomide and especially ibrutinib appear to have a significant activity against this lymphoma and should be incorporated in the treatment of this resistant and aggressive lymphoma. To our knowledge, this is the first case of PCDLBCL-LT reported in the literature exhibiting a complete response to ibrutinib.

  3. Detection Rate and Clinical Impact of Respiratory Viruses in Children with Kawasaki Disease

    Directory of Open Access Journals (Sweden)

    Ja Hye Kim

    2012-12-01

    Full Text Available &lt;B&gt;Purpose:&lt;/B&gt; The purpose of this prospective case-control study was to survey the detection rate of respiratory viruses in children with Kawasaki disease (KD by using multiplex reverse transcriptasepolymerase chain reaction (RT-PCR, and to investigate the clinical implications of the prevalence of respiratory viruses during the acute phase of KD. &lt;B&gt;Methods:&lt;/B&gt; RT-PCR assays were carried out to screen for the presence of respiratory syncytial virus A and B, adenovirus, rhinovirus, parainfluenza viruses 1 to 4, influenza virus A and B, metapneumovirus, bocavirus, coronavirus OC43/229E and NL63, and enterovirus in nasopharyngeal secretions of 55 KD patients and 78 control subjects. &lt;B&gt;Results:&lt;/B&gt; Virus detection rates in KD patients and control subjects were 32.7% and 30.8%, respectively (P=0.811. However, there was no significant association between the presence of any of the 15 viruses and the incidence of KD. Comparisons between the 18 patients with positive RT-PCR results and the other 37 KD patients revealed no significant differences in terms of clinical findings (including the prevalence of incomplete presentation of the disease and coronary artery diameter. &lt;B&gt;Conclusion:&lt;/B&gt; A positive RT-PCR for currently epidemic respiratory viruses should not be used as an evidence against the diagnosis of KD. These viruses were not associated with the incomplete presentation of KD and coronary artery dilatation.

  4. Chemical interaction of B4C, B, and C with Mo/Si layered structures

    International Nuclear Information System (INIS)

    Rooij-Lohmann, V. I. T. A. de; Veldhuizen, L. W.; Zoethout, E.; Yakshin, A. E.; Kruijs, R. W. E. van de; Thijsse, B. J.; Gorgoi, M.; Schaefers, F.; Bijkerk, F.

    2010-01-01

    To enhance the thermal stability, B 4 C diffusion barrier layers are often added to Mo/Si multilayer structures for extreme ultraviolet optics. Knowledge about the chemical interaction between B 4 C and Mo or Si, however is largely lacking. Therefore, the chemical processes during annealing up to 600 deg. C of a Mo/B 4 C/Si layered structure have been investigated in situ with hard x-ray photoelectron spectroscopy and ex situ with depth profiling x-ray photoelectron spectroscopy. Mo/B/Si and Mo/C/Si structures have also been analyzed as reference systems. The chemical processes in these systems have been identified, with two stages being distinguished. In the first stage, B and C diffuse and react predominantly with Mo. MoSi x forms in the second stage. If the diffusion barrier consists of C or B 4 C, a compound forms that is stable up to the maximum probed temperature and annealing time. We suggest that the diffusion barrier function of B 4 C interlayers as reported in literature can be caused by the stability of the formed compound, rather than by the stability of B 4 C itself.

  5. Ordering effects in benzo[1,2-b:4,5-b']difuran-thieno[3,4-c]pyrrole-4,6- dione polymers with >7% solar cell efficiency

    KAUST Repository

    Warnan, Julien; Cabanetos, Clement; El Labban, Abdulrahman; Hansen, Michael Ryan; Tassone, Christopher J.; Toney, Michael F.; Beaujuge, Pierre

    2014-01-01

    Benzo[1,2-b:4,5-b']difuran-thieno[3,4-c]pyrrole-4,6-dione (PBDFTPD) polymers prepared by microwave-assisted synthesis can achieve power conversion efficiencies (PCEs) >7% in bulk-heterojunction solar cells with phenyl-C61/71-butyric acid methyl

  6. Measurement of the mass splittings between the b{bar b}{chi}{sub b,J}(1P) states

    Energy Technology Data Exchange (ETDEWEB)

    Edwards, K.W.; Edwards, K.W. [Institute of Particle Physics (Canada); Bellerive, A.; Bellerive, A.; Janicek, R.; Janicek, R.; MacFarlane, D.B.; MacFarlane, D.B.; Patel, P.M.; Patel, P.M. [Institute of Particle Physics (Canada); Sadoff, A.J. [Ithaca College, Ithaca, New York,14850 (United States); Ammar, R.; Baringer, P.; Bean, A.; Besson, D.; Coppage, D.; Darling, C.; Davis, R.; Kotov, S.; Kravchenko, I.; Kwak, N.; Zhou, L. [University of Kansas, Lawrence, Kansas, 66045 (United States); Anderson, S.; Kubota, Y.; Lee, S.J.; ONeill, J.J.; Poling, R.; Riehle, T.; Smith, A. [University of Minnesota, Minneapolis, Minnesota, 55455 (United States); Alam, M.S.; Athar, S.B.; Ling, Z.; Mahmood, A.H.; Timm, S.; Wappler, F. [State University of New York at Albany, Albany, New York, 12222 (United States); Anastassov, A.; Duboscq, J.E.; Fujino, D.; Gan, K.K.; Hart, T.; Honscheid, K.; Kagan, H.; Kass, R.; Lee, J.; Schwarthoff, H.; Spencer, M.B.; Sung, M.; Undrus, A.; Wolf, A.; Zoeller, M.M. [Ohio State University, Columbus, Ohio, 43210 (United States); Richichi, S.J.; Severini, H.; Skubic, P. [University of Oklahoma, Norman, Oklahoma, 73019 (United States); Bishai, M.; Fast, J.; Hinson, J.W.; Menon, N.; Miller, D.H.; Shibata, E.I.; Shipsey, I.P.; Yurko, M. [Purdue University, West Lafayette, Indiana, 47907 (United States); Glenn, S.; Kwon, Y.; Lyon, A.L.; Roberts, S.; Thorndike, E.H. [University of Rochester, Rochester, New York, 14627 (United States); Jessop, C.P.; Lingel, K.; Marsiske, H.; Perl, M.L.; Savinov, V.; Ugolini, D.; Zhou, X. [Stanford Linear Accelerator Center, Stanford University, Stanford, California, 94309 (United States); Coan, T.E.; Fadeyev, V.; Korolkov, I.; Maravin, Y.; Narsky, I.; Shelkov, V.; Staeck, J.; Stroynowski, R.; Volobouev, I.; Ye, J. [Southern Methodist University, Dallas, Texas, 75275 (United States); Artuso, M.; Azfar, F.; Efimov, A.; Goldberg, M.; He, D.; Kopp, S.; Moneti, G.C.; Mountain, R.; Schuh, S.; Skwarnicki, T.; and others

    1999-02-01

    We present new measurements of photon energies and branching fractions for the radiative transitions {Upsilon}(2S){r_arrow}{gamma}{chi}{sub b(J=0,1,2)}(1P). The masses of the {chi}{sub b} states are determined from the measured radiative photon energies. The ratio of mass splittings between the {chi}{sub b} substates, r{equivalent_to}(M{sub J=2}{minus}M{sub J=1})/(M{sub J=1}{minus}M{sub J=0}), with M the {chi}{sub b} mass, provides information on the nature of the b{bar b} confining potential. We find r(1P)=0.542{plus_minus}0.022{plus_minus}0.024. This value is somewhat lower than the previous world average, but more consistent with the theoretical expectation that r(1P){lt}r(2P); i.e., that this mass splitting ratio is smaller for the {chi}{sub b}(1P) states than for the {chi}{sub b}(2P) states. {copyright} {ital 1999} {ital The American Physical Society}

  7. Identification of a umuDC locus in Salmonella typhimurium LT2

    International Nuclear Information System (INIS)

    Smith, C.M.; Eisenstadt, E.

    1989-01-01

    The umuDC operon of Escherichia coli is required for efficient mutagenesis by UV light and many other DNA-damaging agents. The existence of a umuDC analog in Salmonella typhimurium has been questioned. With DNA probes to the E. coli umuD and umuC genes, we detected, by Southern blot hybridization, sequences similar to both of these genes in S. typhimurium LT2. We also confirmed that the presence of cloned E. coli umuD enhances the UV mutability and resistance of S. typhimurium. Our data strongly suggest that S. typhimurium contains a functional umuDC operon

  8. CD4 T lymphocyte counts in patients undergoing splenectomy during living donor liver transplantation.

    Science.gov (United States)

    Natsuda, Koji; Eguchi, Susumu; Takatsuki, Mistuhisa; Soyama, Akihiko; Hidaka, Masaaki; Hara, Takanobu; Kugiyama, Tota; Baimakhanov, Zhassulan; Ono, Shinichiro; Kitasato, Amane; Fujita, Fumihiko; Kanetaka, Kengo; Kuroki, Tamotsu

    2016-02-01

    The role of splenectomy in increasing the CD4-positive T lymphocyte counts (hereafter: CD4 counts) and the CD4 to CD8 ratio have not yet been fully investigated, especially in the case of HIV-positive patients undergoing liver transplantation (LT). The change in the total lymphocyte counts of 32 patients who underwent one-stage splenectomy with living donor (LD) LT with (n=13) or without rituximab (RTX, n=19) therapy were examined to validate our cohort of ABO-incompatible LDLT with RTX. Subsequently, perioperative changes in CD4 counts and the CD 4 to CD8 ratio were measured in 13 patients who underwent ABO-incompatible LDLT/RTX with splenectomy. (1) The administration of RTX did not significantly affect the total lymphocyte counts of patients after LDLT/splenectomy in any of the observation periods. (2) The CD4 counts were significantly higher at 2years after LDLT in comparison to the perioperative CD4 counts but not within the 3-month period (p=0.039). The CD4/CD8 ratio gradually decreased after LDLT/splenectomy under RTX treatment. An immediate increase in the CD4 counts therefore cannot be expected after LDLT with splenectomy. The total lymphocyte and CD4 counts were rather stable in the peritransplant period even in ABO incompatible LDLT with RTX. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. 12 CFR Appendix B to Subpart B of... - Article 4A, Funds Transfers

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 2 2010-01-01 2010-01-01 false Article 4A, Funds Transfers B Appendix B to...—Article 4A, Funds Transfers Part 1—Subject Matter and Definitions Section 4A-101. Short Title This Article... otherwise provided in section 4A-108, this Article applies to funds transfers defined in section 4A-104...

  10. Bronchial effects of leukotriene D4 inhalation in normal human lung

    DEFF Research Database (Denmark)

    Bisgaard, H; Groth, S

    1987-01-01

    obstruction had decreased by 50% of the maximum effect, and no delayed reaction was observed within 10 h. The reactivity of the airways did not change during 10 h after inhalation of LTD4 as tested by repeated exercise challenges. Pretreatment with ipratropium bromide prevented the effect of LTD4 on FEV1, yet...

  11. Quadruplex genotype analysis at HumTH01, HumTPOX, HumCSF1PO and amelogenin Loci by FoLT-PCR

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Y.H.; Lim, S.K.; Kang, P.W.; Choi, D.H.; Yoon, S.R.; Han, M.S. [National Institute of Scientific Investigation, Seoul (Korea)

    1999-06-01

    A simple and rapid procedure, called FoLT-PCR(Formamide Low Temperature-Polymerase Chain Reaction) was applied to amplifying DNA directly from various forensic biological evidences including human blood, saliva, hair root, or semen without any DNA preparative steps. We added washing step with non-ionic detergent, 1% Triton X-100, and used Taq DNA polymerase instead of Tth DNA polymerase to amplify 3 STR loci and gender allele simultaneously. Optimal concentration of formamide and annealing temperature were determined empirically to 8%(v/v), and 48{sup o} C respectively. We also compared this method with standard PCR. 8 refs., 4 figs.

  12. Synthesis of leukotrienes labelled with deuterium: [11,12,14,15-2H4]-LTA4, -LTC4, -LTD4 and -LTE4

    International Nuclear Information System (INIS)

    Lellouche, J.P.; Aubert, F.; Noel, J.P.; Boullais, C.; Beaucourt, J.P.

    1989-01-01

    Semi-hydrogenation by D 2 gas on Lindlar catalyst of an acetylenic precursor led to [11,12,14,15- 2 H 4 ]-LTA 4 methyl ester. Nucleophilic opening of the epoxide ring by amino thioacids accorded, after saponification, the corresponding deuterated peptidoleukotrienes LTC 4 , LTD 4 and LTE 4 . (author)

  13. B7-2 expressed on EL4 lymphoma suppresses antitumor immunity by an interleukin 4-dependent mechanism.

    Science.gov (United States)

    Stremmel, C; Greenfield, E A; Howard, E; Freeman, G J; Kuchroo, V K

    1999-03-15

    For T cells to become functionally activated they require at least two signals. The B7 costimulatory molecules B7-1 and B7-2 provide the "second signal" pivotal for T cell activation. In this report, we studied the relative roles of B7-1 and B7-2 molecules in the induction of antitumor immunity to the T cell thymoma, EL4. We generated EL4 tumor cells that expressed B7-1, B7-2, and B7-1+B7-2 by transfecting murine cDNAs. Our results demonstrate that EL4-B7-1 cells are completely rejected in syngeneic mice. Unlike EL4-B7-1 cells, we find that EL4-B7-2 cells are not rejected but progressively grow in the mice. A B7-1- and B7-2-EL4 double transfectant was generated by introducing B7-2 cDNA into the EL4-B7-1 tumor line that regressed in vivo. The EL4-B7-1+B7-2 double transfectant was not rejected when implanted into syngeneic mice but progressively grew to produce tumors. The double transfectant EL4 cells could costimulate T cell proliferation that could be blocked by anti-B7-1 antibodies, anti-B7-2 antibodies, or hCTLA4 immunoglobulin, showing that the B7-1 and B7-2 molecules expressed on the EL4 cells were functional. In vivo, treatment of mice implanted with double-transfected EL4 cells with anti-B7-2 monoclonal antibody resulted in tumor rejection. Furthermore, the EL4-B7-2 and EL4-B7-1+B7-2 cells, but not the wild-type EL4 cells, were rejected in interleukin 4 (IL-4) knockout mice. Our data suggests that B7-2 expressed on some T cell tumors inhibits development of antitumor immunity, and IL-4 appears to play a critical role in abrogation of the antitumor immune response.

  14. Systems Li[sub 2]B[sub 4]O[sub 7] (Na[sub 2]B[sub 4]O[sub 7], K[sub 2]B[sub 4]O[sub 7])-N[sub 2]H[sub 3]H[sub 4]OH-H[sub 2]O at 25 deg C. Sistemy Li[sub 2]B[sub 4]O[sub 7] (Na[sub 2]B[sub 4]O[sub 7], K[sub 2]B[sub 4]O[sub 7])-N[sub 2]H[sub 3]H[sub 4]OH-H[sub 2]O pri 25 grad S

    Energy Technology Data Exchange (ETDEWEB)

    Skvortsov, V G; Sadetdinov, Sh V; Akimov, V M; Mitrasov, Yu N; Petrova, O V; Klopov, Yu N [Chuvashskij Gosudarstvennyj Pedagogicheskij Inst., Cheboksary (Russian Federation) Universitet Druzhby Narodov, Moscow (Russian Federation)

    1994-02-01

    Phase equilibriums in the Li[sub 2]B[sub 4]O[sub 7] (Na[sub 2]B[sub 4]O[sub 7], K[sub 2]B[sub 4]O[sub 7])-N[sub 2]H[sub 3]H[sub 4]OH-H[sub 2]O systems were investigated by methods of isothermal solubility, refractometry and PH-metry at 25 deg C for the first time. Lithium and sodium tetraborates was established to form phases of changed composition mM[sub 2]B[sub 4]O[sub 7][center dot]nN[sub 2]H[sub 3]C[sub 2]H[sub 4]OH[center dot]XH[sub 2]O, where M=Li, Na with hydrazine ethanol. K[sub 2]B[sub 4]O[sub 7][center dot]4H[sub 2]O precipitates in solid phase in the case of potassium salt. Formation of isomorphous mixtures was supported by X-ray diffraction and IR spectroscopy methods.

  15. Diabetes mellitus may affect the long-term survival of hepatitis B virus-related hepatocellular carcinoma patients after liver transplantation.

    Science.gov (United States)

    Zhang, Qing; Deng, Yong-Lin; Liu, Chang; Huang, Li-Hong; Shang, Lei; Chen, Xin-Guo; Wang, Le-Tian; Du, Jin-Zan; Wang, Ying; Wang, Pei-Xiao; Zhang, Hui; Shen, Zhong-Yang

    2016-11-21

    To determine whether diabetes mellitus (DM) affects prognosis/recurrence after liver transplantation (LT) for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). A retrospective study was conducted between January 2000 and August 2013 on 1631 patients with HBV-related HCC who underwent LT with antiviral prophylaxis. Patient data were obtained from the China Liver Transplant Registry (https://www.cltr.org/). To compare the outcomes and tumor recurrence in the HBV-related HCC patients with or without DM, statistical analyses were conducted using χ 2 tests, Mann-Whitney tests, the Kaplan-Meier method, log-rank tests and multivariate step-wise Cox regression analysis. Univariate analysis of 1631 patients who underwent LT found overall 1-, 3- and 5-year survival rates of 79%, 73% and 71% respectively in the DM patients, and 84%, 78% and 76% in the non-DM patients respectively. Overall survival rate differences after LT between the two groups were significant ( P = 0.041), but recurrence-free survival rates were not ( P = 0.096). By stratified analysis, the overall survival rates in DM patients for age > 50 years ( P = 0.002), the presence of vascular invasion ( P = 0.096), tumors ≤ 3 cm ( P = 0.047), two to three tumor nodules ( P = 0.007), Child-Pugh grade B ( P = 0.018), and pre-LT alanine aminotransferase levels between 40 and 80 IU/L ( P = 0.017) were significantly lower than in non-DM patients. Additionally, serum α-fetoprotein level > 2000 ng/mL ( P = 0.052) was associated with a significant survival difference trend between DM and non-DM patients. Multivariate analysis showed that the presence of DM ( P < 0.001, HR = 1.591; 95%CI: 1.239-2.041) was an independent predictor associated with poor survival after LT. HBV-related HCC patients with DM have decreased long-term overall survival and poor LT outcomes. Prevention strategies for HCC patients with DM are recommended.

  16. Trace fossils from the eocene Lillebælt clay formation, Røsnæs Peninsula, Denmark

    DEFF Research Database (Denmark)

    Nielsen, Jan Kresten; Milàn, Jesper; Mesfun, Daniel

    2015-01-01

    A cliff exposure of the Eocene Lillebælt Clay Formation, on the Røsnæs peninsula of Zealand, Denmark, has yielded a diverse trace-fossil assemblage. The trace fossils are described formally for the first time and assigned to Phymatoderma melvillensis, unnamed clusters of small burrows, Ophiomorpha...

  17. EphB4 promotes or suppresses Ras/MEK/ERK pathway in a context-dependent manner: Implications for EphB4 as a cancer target.

    Science.gov (United States)

    Xiao, Zhan; Carrasco, Rosa; Kinneer, Krista; Sabol, Darrin; Jallal, Bahija; Coats, Steve; Tice, David A

    2012-06-01

    EphB4 is a member of the Eph receptor tyrosine kinase family shown to act in neuronal guidance and mediate venal/arterial separation. In contrast to these more established roles, EphB4's function in cancer is much less clear. Here we illustrate both tumor promoting as well as suppressing roles of EphB4, by showing that its activation resulted in inhibition of the Ras/ERK pathway in endothelial cells but activation of the same pathway in MCF-7 breast cancer cells. This was true if EphB4 was stimulated with EphrinB2, its natural ligand, or an agonistic monoclonal antibody for EphB4. Correspondingly, EphB4 activation stimulated MCF7 growth while inhibiting HUVEC cell proliferation. The reason for these dramatic differences is due to functional coupling of EphB4 to different downstream effectors. Reduction of p120 RasGAP in HUVEC cells attenuated the inhibitory effect of EphB4 activation on the ERK pathway, whereas knockdown of PP2A in MCF7 cells attenuated EphB4 activation of the ERK pathway. This represents the first time a functional coupling between Eph receptor and PP2A has been demonstrated leading to activation of an oncogenic pathway. Our study illustrates the caveats and potential challenges of targeting EphB4 for cancer therapy due to the conflicting effects on cancer cell and endothelial cell compartments.

  18. Inhibition of release of inflammatory mediators in primary and cultured cells by a Chinese herbal medicine formula for allergic rhinitis

    Directory of Open Access Journals (Sweden)

    McPhee Sarah

    2007-02-01

    Full Text Available Abstract Background We demonstrated that a Chinese herbal formula, which we refer to as RCM-101, developed from a traditional Chinese medicine formula, reduced nasal and non-nasal symptoms of seasonal allergic rhinitis (SAR. The present study in primary and cultured cells was undertaken to investigate the effects of RCM-101 on the production/release of inflammatory mediators known to be involved in SAR. Methods Compound 48/80-induced histamine release was studied in rat peritoneal mast cells. Production of leukotriene B4 induced by the calcium ionophore A23187 was studied in porcine neutrophils using an HPLC assay and lipopolysaccharide-stimulated prostaglandin E2 production was studied in murine macrophage (Raw 264.7 cells by immune-enzyme assay. Expression of cyclooxygenase-1 (COX-1 and cyclooxygenase-2 (COX-2 was determined in Raw 264.7 cells, using western blotting techniques. Results RCM-101 (1–100 μg/mL produced concentration-dependent inhibition of compound 48/80-induced histamine release from rat peritoneal mast cells and of lipopolysaccharide-stimulated prostaglandin E2 release from Raw 264.7 cells. Over the range 1 – 10 μg/mL, it inhibited A23187-induced leukotriene B4 production in porcine neutrophils. In addition, RCM-101 (100 μg/mL inhibited the expression of COX-2 protein but did not affect that of COX-1. Conclusion The findings indicate that RCM-101 inhibits the release and/or synthesis of histamine, leukotriene B4 and prostaglandin E2 in cultured cells. These interactions of RCM-101 with multiple inflammatory mediators are likely to be related to its ability to reduce symptoms of allergic rhinitis.

  19. Effects of sulfur oxides on eicosanoids

    International Nuclear Information System (INIS)

    Chen, L.C.; Miller, P.D.; Amdur, M.O.

    1989-01-01

    Ultrafine metal oxides and SO2 react during coal combustion or smelting operations to form primary emissions coated with an acidic SOx layer. Ongoing work in this laboratory has examined the effects of sulfur oxides on pulmonary functions of guinea pigs. We have previously reported that 20 micrograms/m3 acidic sulfur oxide as a surface layer on ultrafine ZnO particles decreases lung volumes, decreases carbon monoxide diffusing capacity, and causes lung inflammation in guinea pigs after 4 daily 3-h exposures. It also produces bronchial hypersensitivity following a single 1-h exposure. The importance of this surface layer is demonstrated by our observation that 200 micrograms/m3 of sulfuric acid droplets of equivalent size are needed to produce the same degree of hypersensitivity. This study characterized the concentration-dependent effects of in vivo exposures to sulfur oxides on arachidonic acid metabolism in the guinea pig lung, and investigated the time course and the relation between eicosanoid composition and pulmonary functions. We focused specifically on four cyclooxygenase metabolites of arachidonic acid, that is, prostaglandins (PG) E1, F2 alpha, 6-keto prostaglandin F1 alpha, and thromboxane (Tx) B2, and two groups of sulfidopeptide leukotrienes (C4, D4, E4, and F4). Guinea pigs were exposed to ultrafine ZnO aerosol (count median diameter = 0.05 microns, sigma g = 1.80) with a layer of acidic sulfur oxide on the surface of the particles. Lung lavage was collected after exposures, and the levels of arachidonic acid metabolites were determined using radioimmunoassay (RIA). Concentration-dependent promotion of PGF2 alpha and concentration-dependent suppression of LtB4 were observed. The increased PGF2 alpha was associated with depressed vital capacity and diffusing capacity of the lungs measured in guinea pigs exposed to the same atmosphere described in a previous study

  20. Higher susceptibility of NOD/LtSz-scid Il2rg−/− NSG mice to xenotransplanted lung cancer cell lines

    International Nuclear Information System (INIS)

    Kanaji, Nobuhiro; Tadokoro, Akira; Susaki, Kentaro; Yokokura, Saki; Ohmichi, Kiyomi; Haba, Reiji; Watanabe, Naoki; Bandoh, Shuji; Ishii, Tomoya; Dobashi, Hiroaki; Matsunaga, Takuya

    2014-01-01

    No lung cancer xenograft model using non-obese diabetic (NOD)-scid Il2rg −/− mice has been reported. The purpose of this study is to select a suitable mouse strain as a xenogenic host for testing tumorigenicity of lung cancer. We directly compared the susceptibility of four immunodeficient mouse strains, c-nu, C.B-17 scid, NOD-scid, and NOD/LtSz-scid Il2rg −/− (NSG) mice, for tumor formation from xenotransplanted lung cancer cell lines. Various numbers (10 1 –10 5 cells/head) of two lung cancer cell lines, A549 and EBC1, were subcutaneously inoculated and tumor sizes were measured every week up to 12 weeks. When 10 4 EBC1 cells were inoculated, no tumor formation was observed in BALB/c-nu or C.B-17 scid mice. Tumors developed in two of the five NOD-scid mice (40%) and in all the five NSG mice (100%). When 10 3 EBC1 cells were injected, no tumors developed in any strain other than NSG mice, while tumorigenesis was achieved in all the five NSG mice (100%, P=0.0079) within 9 weeks. NSG mice similarly showed higher susceptibility to xenotransplantation of A549 cells. Tumor formation was observed only in NSG mice after inoculation of 10 3 or fewer A549 cells (40% vs 0% in 15 NSG mice compared with others, respectively, P=0.0169). We confirmed that the engrafted tumors originated from inoculated human lung cancer cells by immunohistochemical staining with human cytokeratin and vimentin. NSG mice may be the most suitable strain for testing tumorigenicity of lung cancer, especially if only a few cells are available

  1. Utility of a multiplex reverse transcriptasepolymerase chain reaction assay (HemaVision in the evaluation of genetic abnormalities in Korean children with acute leukemia: a single institution study

    Directory of Open Access Journals (Sweden)

    Hye-Jin kim

    2013-06-01

    Full Text Available &lt;b&gt;Purpose:&lt;/b&gt; In children with acute leukemia, bone marrow genetic abnormalities (GA have prognostic significance, and may be the basis for minimal residual disease monitoring. Since April 2007, we have used a multiplex reverse transcriptase-polymerase chain reaction tool (HemaVision to detect of GA. &lt;b&gt;Methods:&lt;/b&gt; In this study, we reviewed the results of HemaVision screening in 270 children with acute leukemia, newly diagnosed at The Catholic University of Korea from April 2007 to December 2011, and compared the results with those of fluorescence in situ hybridization (FISH, and G-band karyotyping. &lt;b&gt;Results:&lt;/b&gt; Among the 270 children (153 males, 117 females, 187 acute lymphoblastic leukemia and 74 acute myeloid leukemia patients were identified. Overall, GA was detected in 230 patients (85.2%. HemaVision, FISH, and G-band karyotyping identified GA in 125 (46.3%, 126 (46.7%, and 215 patients (79.6%, respectively. TEL-AML1 (20.9%, 39/187 and AML1-ETO (27%, 20/74 were the most common GA in ALL and AML, respectively. Overall sensitivity of HemaVision was 98.4%, with false-negative results in 2 instances: 1 each for TEL-AML1 and MLL-AF4 . An aggregate of diseasesspecific FISH showed 100% sensitivity in detection of GA covered by HemaVision for actual probes utilized. G-band karyotype revealed GA other than those covered by HemaVison screening in 133 patients (49.3%. Except for hyperdiplody and hypodiploidy, recurrent GA as defined by the World Health Organizationthat were not screened by HemaVision, were absent in the karyotype. &lt;b&gt;Conclusion:&lt;/b&gt; HemaVision, supported by an aggregate of FISH tests for important translocations, may allow for accurate diagnosis of GA in Korean children with acute leukemia.

  2. Tüketim kültüründe etkili bir araç olarak reklamın işlevlerine dair genel bir değerlendirme

    OpenAIRE

    Elmasoğlu, Kamile

    2017-01-01

    Betimsel analiz yönteminin kullanıldığı bu çalışmada, tüketim kültürünün yayılmasında etkili bir araç olarak görülen reklamın rolüne dair genel bir değerlendirme sunmak hedeflenmektedir. Bu hedef dâhilinde, tüketim toplumu, tüketim kültürü ve reklamın tüketim kültürü içindeki işlevleri; çeşitli düşünürlerin görüşlerinden istifade edilerek tartışılmıştır. Tüketim kültürünün hakim olduğu bir toplumda reklama ilişkin çeşitli fikirlerin benimsendiği görülmektedir. Çalışma genel olarak değerlendir...

  3. Käyttäjien tuottama sisältö markkinoinnissa : Opas

    OpenAIRE

    Koskenseppä, Mikko

    2016-01-01

    Markkinoijien ja kuluttajien roolit ovat muuttunut 2000-luvun aikana, jonka takia yritykset eivät voi enää pitää markkinointia yksisuuntaisena viestintänä. Nykyään yrityksien pitää saada kuluttajat mukaan markkinointiin, ja käyttäjien tuottama sisältö onkin yksi ratkaisu tähän ongelmaan. Tämä opinnäytetyö oli toiminnallinen työ. Sen tavoitteena oli luoda ohjeistus käyttäjien tuottaman sisällön käyttämisestä markkinoinnissa. Työn muut tavoitteet oli selvittää sen tuomat hyödyt ja ominaisuu...

  4. The effect of magnetic storm on the bottomside profile parameters B0 and

    International Nuclear Information System (INIS)

    Adeniyi, J.O.; Radicella, S.M.

    2001-01-01

    We have used data from an equatorial station for the investigation of magnetic storm effects on B0 and B1. Three storm events, which occurred in January, April and October of a low solar activity year (1995), were used for the study. B0 is the parameter that is mostly affected and the effect is concentrated on the daytime period (0700-1700LT). (author)

  5. PREFACE: Proceedings of the 25th International Conference on Low Temperature Physics (LT25) (Amsterdam, The Netherlands, 6-13 August 2008) Proceedings of the 25th International Conference on Low Temperature Physics (LT25) (Amsterdam, The Netherlands, 6-13 August 2008)

    Science.gov (United States)

    Kes, Peter; Jochemsen, Reijer

    2009-04-01

    This issue forms part I of the Proceedings of the 25th International Conference on Low Temperature Physics (LT25) (Amsterdam, The Netherlands, 67-13 August 2008). The majority of the special invited lectures, such as the London prize lectures, the international union of pure and applied physics (IUPAP) young scientist award lectures, the plenary, half-plenary and public lectures, and the historical lectures presented at the LT25 conference, are included. The papers relating to the oral and poster presentations will appear in part II of the proceedings in a dedicated open access issue of Journal of Physics: Conference Series (2009 J. Phys.: Conf. Ser. 150). In addition to the organizer's report and a summary of the new developments in low temperature physics, which can also be found in this issue, part II provides useful information about LT25, such as an overview of committees, sponsors, exhibitors, and some conference statistics. To ensure the high publication standard mandated by Journal of Physics: Condensed Matter and Journal of Physics: Conference Series every paper was reviewed by at least one referee before it was accepted for publication. The editors are indebted to many colleagues for invaluable assistance in the preparation and review of 900 papers appearing in both parts I and II of these proceedings. In particular, we would like to thank Carlo Beenakker, Jeroen van den Brink, Hans Brom, Jos de Jongh, Horst Rogalla, Fons de Waele, and Jan Zaanen.

  6. WARM SPITZER PHOTOMETRY OF THREE HOT JUPITERS: HAT-P-3b, HAT-P-4b AND HAT-P-12b

    Energy Technology Data Exchange (ETDEWEB)

    Todorov, Kamen O. [Department of Astronomy and Astrophysics, Pennsylvania State University, University Park, PA 16802 (United States); Deming, Drake [Department of Astronomy, University of Maryland at College Park, College Park, MD 20742 (United States); Knutson, Heather A. [Division of Geological and Planetary Sciences, California Institute of Technology, Pasadena, CA 91125 (United States); Burrows, Adam [Department of Astrophysical Sciences, Princeton University, Princeton, NJ 08544 (United States); Fortney, Jonathan J.; Laughlin, Gregory [Department of Astronomy and Astrophysics, University of California at Santa Cruz, Santa Cruz, CA 95064 (United States); Lewis, Nikole K. [Department of Earth, Atmospheric, and Planetary Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Cowan, Nicolas B. [Department of Physics and Astronomy, Northwestern University, Evanston, IL 60208 (United States); Agol, Eric [Department of Astronomy, University of Washington, Box 351580, Seattle, WA 98195 (United States); Desert, Jean-Michel [Astronomy Department, California Institute of Technology, Pasadena, CA 91125 (United States); Sada, Pedro V. [Department of Physics and Mathematics, University of Monterrey, Monterrey (Mexico); Charbonneau, David [Harvard-Smithsonian Center for Astrophysics, Cambridge, MA 02138 (United States); Langton, Jonathan [Department of Physics, Principia College, Elsah, IL 62028 (United States); Showman, Adam P. [Lunar and Planetary Laboratory, University of Arizona, Tucson, AZ 85721 (United States)

    2013-06-20

    We present Warm Spitzer/IRAC secondary eclipse time series photometry of three short-period transiting exoplanets, HAT-P-3b, HAT-P-4b and HAT-P-12b, in both the available 3.6 and 4.5 {mu}m bands. HAT-P-3b and HAT-P-4b are Jupiter-mass objects orbiting an early K and an early G dwarf star, respectively. For HAT-P-3b we find eclipse depths of 0.112%+0.015%-0.030% (3.6 micron) and 0.094%+0.016%-0.009% (4.5 {mu}m). The HAT-P-4b values are 0.142%+0.014%-0.016% (3.6 micron) and 0.122%+0.012%-0.014% 4.5 {mu}m). The two planets' photometry is consistent with inefficient heat redistribution from their day to night sides (and low albedos), but it is inconclusive about possible temperature inversions in their atmospheres. HAT-P-12b is a Saturn-mass planet and is one of the coolest planets ever observed during secondary eclipse, along with the hot Neptune GJ 436b and the hot Saturn WASP-29b. We are able to place 3{sigma} upper limits on the secondary eclipse depth of HAT-P-12b in both wavelengths: <0.042% (3.6 {mu}m) and <0.085% (4.5 {mu}m). We discuss these results in the context of the Spitzer secondary eclipse measurements of GJ 436b and WASP-29b. It is possible that we do not detect the eclipses of HAT-P-12b due to high eccentricity, but find that weak planetary emission in these wavelengths is a more likely explanation. We place 3{sigma} upper limits on the |e cos {omega}| quantity (where e is eccentricity and {omega} is the argument of periapsis) for HAT-P-3b (<0.0081) and HAT-P-4b (<0.0042), based on the secondary eclipse timings.

  7. USA kohus nõuab LHV-lt, Lepikult ja Peegilt kiiresti ligi 14 miljonit krooni / Lauri Matsulevitsh

    Index Scriptorium Estoniae

    Matsulevitsh, Lauri

    2005-01-01

    USA kohus kinnitas investeerimispangaga LHV eelkokkuleppe ning muutis esialgset hagi tagamise määrust, millega nõuab LHV-lt sealt välja viidud raha USA kohturegistri kontole tagasi viie päeva jooksul. Lisa: Kontodelt nõutakse 13,8 mln krooni. Vt. samas: Advokaat: SEC kasutab jõupositsiooni

  8. B-physics in hadron colliders

    International Nuclear Information System (INIS)

    Hill, C.T.

    1993-01-01

    A program of producing > 10 10 detectable B's is conservatively achievable within this decade. This offers an excellent conventional physics program of ∼ 10 9 B→D * ell ν decays and ∼10 5 B→ρ ell ν decays, allowing a determination of V cb ± 3% and V ub ± 20%. This also probes the quantities such as √B(f B ) and f B s with high statistics. The resonances of the B-system and the prospects for flavor and kinematic tagging will emerge within the next few years. New states such as B c will be surveyed, and the list of B s and B c decay modes will grow. CP-violation with conventional or bachelor pion tagging may be first observed in the ψK S asymmetry within such a 10 10 program. B S bar B S mixing looks difficult, though x s approx-lt 20 may be probed. Rare and radiative dacays will be subject to their first probative examination

  9. Contact Lens-Induced Discomfort and Inflammatory Mediator Changes in Tears.

    Science.gov (United States)

    Masoudi, Simin; Zhao, Zhenjun; Stapleton, Fiona; Willcox, Mark

    2017-01-01

    Studies indicate that contact lens (CL) discontinuation mostly occurs because of dryness and discomfort symptoms. This study aimed to investigate relationships between changes in the concentration of tear inflammatory mediators with subjective comfort ratings with CL wear and no contact lens wear between morning and evening. Forty-five subjects collected tears twice daily in the morning and in the evening with or without lenses. Comfort was rated subjectively on a scale from 1 to 100 (where 100 was extremely comfortable) just before each tear collection. Tear samples were assayed for complement components (C3 and C3a), leukotriene B4 (LTB4), secretory phospholipase A2 (sPLA2), secretory immunoglobulin A (sIgA), and bradykinin using commercially available immuno-based assay kits. Comfort ratings showed a statistically significant decline from morning to evening both with CL (89.0±10.1 AM vs. 76.7±15.2 PM; P0.05). Leukotriene B4 levels were slightly higher in CL (CL 43.4±12.6 pg/ml vs. No CL 39.4±13.4 pg/mL; P=0.034), whereas the concentration of LTB4, C3, C3a, and sIgA dropped by the end of the day in the presence or absence of lens wear (Ptear levels were not correlated with comfort ratings in any of the conditions. Leukotriene B4 had a higher concentration in the evening, and when measured as a ratio to sIgA, there was a trend for increased concentration of this mediator during CL wear. Although specific mediators showed changes from morning to evening with and without lens wear, most of these were not correlated with subjective comfort ratings in lens wear. The only mediator that showed an increase in concentration during the day and during lens wear was LTB4, and further studies on this mediator are warranted.

  10. Türk Sucuklarında Ticari Starter Kültür Kullanımı Üzerine Araştırmalar II. Duyusal ve Mikrobiyolojik Analizler

    Directory of Open Access Journals (Sweden)

    Halil Vural

    2015-02-01

    Full Text Available Bu çalışmada; işletme düzeyinde kontrollü koşullarda Türk sucuğu üretiminde ticari starter kültürlerin kullanımı incelenmiştir. Bu amaçla, starter kültür katılmayan örnek kontrol grubu olarak alınarak, 7 farklı ticari starter kültürle hazırlanan 8 sucuk örneği aynı koşullarda denemeye alınmıştır. Sucuklara üretimin 7 kritik noktasına mezofilik aerobik bakteri, Lactobacillus-Pedicoccus ve patojen olmayan Staphylococcus-Micrococcus sayımı analizleri ile ürün bazında duyusal analizlerle starter kültür katılarak üretilen sucukların kontrol grubuna göre belirgin üstünlük sağladıkları belirlenmiş, kimyasal, mikrobiyolojik ve duyusal analiz bulgularının birlikte değerlendirilmesi; Türk sucuğu özelliklerine en uygun sonuçları Flora Carn SL ve Flora Carn SP starter kültürleri ile yapılan sucukların verdiğini göstermiştir.

  11. Effect of the Ti/B4C mole ratio on the reaction products and reaction mechanism in an Al–Ti–B4C powder mixture

    International Nuclear Information System (INIS)

    Zhang, Jingjing; Lee, Jung-Moo; Cho, Young-Hee; Kim, Su-Hyeon; Yu, Huashun

    2014-01-01

    The effect of the Ti/B 4 C mole ratio on the fabrication behavior of Al composites is investigated using Al–Ti–B 4 C powder mixtures as reactants. The quick spontaneous infiltration (QSI) process combined with the combustion reaction and DTA analysis were used. According to the thermodynamic predictions, which are verified in the experimental results, TiB 2 is formed in all the samples whereas TiC is only formed in reactants with a Ti/B 4 C mole ratio of more than two. The C atoms from the reacted B 4 C do not move into TiC but instead they move into Al 3 BC or Al 4 C 3 when the Ti/B 4 C mole ratio is less than two. In addition, the reaction mechanism with a Ti/B 4 C mole ratio of 0.75 is investigated extensively. - Highlights: • The critical role of the Ti/B 4 C mole ratio on the reaction products of Al–Ti–B 4 C was studied using experiments. • The experimental results are also supported by thermodynamic calculations presented in this paper. • The reaction mechanism with a Ti/B 4 C mole ratio of 0.75 is investigated extensively

  12. Photoelectron spectroscopy of B4O4 (-): Dual 3c-4e π hyperbonds and rhombic 4c-4e o-bond in boron oxide clusters.

    Science.gov (United States)

    Tian, Wen-Juan; Zhao, Li-Juan; Chen, Qiang; Ou, Ting; Xu, Hong-Guang; Zheng, Wei-Jun; Zhai, Hua-Jin; Li, Si-Dian

    2015-04-07

    Gas-phase anion photoelectron spectroscopy (PES) is combined with global structural searches and electronic structure calculations at the hybrid Becke 3-parameter exchange functional and Lee-Yang-Parr correlation functional (B3LYP) and single-point coupled-cluster with single, double, and perturbative triple excitations (CCSD(T)) levels to probe the structural and electronic properties and chemical bonding of the B4O4 (0/-) clusters. The measured PES spectra of B4O4 (-) exhibit a major band with the adiabatic and vertical detachment energies (ADE and VDE) of 2.64 ± 0.10 and 2.81 ± 0.10 eV, respectively, as well as a weak peak with the ADE and VDE of 1.42 ± 0.08 and 1.48 ± 0.08 eV. The former band proves to correspond to the Y-shaped global minimum of Cs B4O4 (-) ((2)A″), with the calculated ADE/VDE of 2.57/2.84 eV at the CCSD(T) level, whereas the weak band is associated with the second lowest-energy, rhombic isomer of D2h B4O4 (-) ((2)B2g) with the predicted ADE/VDE of 1.43/1.49 eV. Both anion structures are planar, featuring a B atom or a B2O2 core bonded with terminal BO and/or BO2 groups. The same Y-shaped and rhombic structures are also located for the B4O4 neutral cluster, albeit with a reversed energy order. Bonding analyses reveal dual three-center four-electron (3c-4e) π hyperbonds in the Y-shaped B4O4 (0/-) clusters and a four-center four-electron (4c-4e) π bond, that is, the so-called o-bond in the rhombic B4O4 (0/-) clusters. This work is the first experimental study on a molecular system with an o-bond.

  13. Differential effects of BDNF and neurotrophin 4 (NT4) on endocytic sorting of TrkB receptors.

    Science.gov (United States)

    Proenca, Catia C; Song, Minseok; Lee, Francis S

    2016-08-01

    Neurotrophins are a family of growth factors playing key roles in the survival, development, and function of neurons. The neurotrophins brain-derived neurotrophic factor (BDNF) and NT4 both bind to and activate TrkB receptors, however, they mediate distinct neuronal functions. The molecular mechanism of how TrkB activation by BDNF and NT4 leads to diverse outcomes is unknown. Here, we report that BDNF and NT4 lead to differential endocytic sorting of TrkB receptors resulting in diverse biological functions in cultured cortical neurons. Fluorescent microscopy and surface biotinylation experiments showed that both neurotrophins stimulate internalization of TrkB with similar kinetics. Exposure to BDNF for 2-3 h reduced the surface pool of TrkB receptors to half, whereas a longer treatment (4-5 h) with NT4 was necessary to achieve a similar level of down-regulation. Although BDNF and NT4 induced TrkB phosphorylation with similar intensities, BDNF induced more rapid ubiquitination and degradation of TrkB than NT4. Interestingly, TrkB receptor ubiquitination by these ligands have substantially different pH sensitivities, resulting in varying degrees of receptor ubiquitination at lower pH levels. Consequently, NT4 was capable of maintaining longer sustained downstream signaling activation that correlated with reduced TrkB ubiquitination at endosomal pH. Thus, by leading to altered endocytic trafficking itineraries for TrkB receptors, BDNF and NT4 elicit differential TrkB signaling in terms of duration, intensity, and specificity, which may contribute to their functional differences in vivo. The neurotrophins, brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4), both bind to and activate TrkB receptors, however, they mediate distinct neuronal functions. Here, we propose that BDNF and NT4 lead to differential endocytic sorting of TrkB receptors resulting in diverse biological functions. BDNF induces more rapid ubiquitination and degradation of TrkB than NT4

  14. The effects of LT-SN on energy dissipation and lifetime in wireless sensor networks

    Directory of Open Access Journals (Sweden)

    Zeydin Pala

    2016-11-01

    Full Text Available Wireless sensor networks (WSNs still attract the attention of researchers, users and the private sector despite their low power and low range tendency for malfunction. This attraction towards WSNs results from their low cost structure and the solutions they offer for many prevalent problems. Many conditions, which remain unforeseen or unexpected during the design of the system, may arise after the initialization of the system. Similarly, many situations where security vulnerabilities take place may emerge in time in WSNs operating normally. In this study, we called nodes which enter sleeping mode without any further waking up and causing a sparser number of nodes in the network without any function in data transmission as Long-Term Sleep Nodes (LT-SN; and considered energy spaces caused by such nodes as a problem; and established two Linear Programming (LP models based on the efficiency of the present nodes. We offered two different models which present the effect of sensor nodes, which were initially operating in wireless sensor network environment and did not wake up following sleep mode, on network lifetime. The results of the present study report that as the number of LT-SN increases, the lifetime of the network decreases.

  15. Celecoxib and tauro-ursodeoxycholic acid co-treatment inhibits cell growth in familial adenomatous polyposis derived LT97 colon adenoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Heumen, Bjorn W.H. van, E-mail: b.vanheumen@mdl.umcn.nl [Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Roelofs, Hennie M.J.; Morsche, Rene H.M. te [Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Marian, Brigitte [Institute of Cancer Research, Wien University, Vienna (Austria); Nagengast, Fokko M.; Peters, Wilbert H.M. [Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands)

    2012-04-15

    Chemoprevention would be a desirable strategy to avoid duodenectomy in patients with familial adenomatous polyposis (FAP) suffering from duodenal adenomatosis. We investigated the in vitro effects on cell proliferation, apoptosis, and COX-2 expression of the potential chemopreventives celecoxib and tauro-ursodeoxycholic acid (UDCA). HT-29 colon cancer cells and LT97 colorectal micro-adenoma cells derived from a patient with FAP, were exposed to low dose celecoxib and UDCA alone or in combination with tauro-cholic acid (CA) and tauro-chenodeoxycholic acid (CDCA), mimicking bile of FAP patients treated with UDCA. In HT-29 cells, co-treatment with low dose celecoxib and UDCA resulted in a decreased cell growth (14-17%, p < 0.01). A more pronounced decrease (23-27%, p < 0.01) was observed in LT97 cells. Cell growth of HT-29 cells exposed to 'artificial bile' enriched with UDCA, was decreased (p < 0.001), either in the absence or presence of celecoxib. In LT97 cells incubated with 'artificial bile' enriched with UDCA, cell growth was decreased only in the presence of celecoxib (p < 0.05). No clear evidence was found for involvement of proliferating cell nuclear antigen, caspase-3, or COX-2 in the cellular processes leading to the observed changes in cell growth. In conclusion, co-treatment with low dose celecoxib and UDCA has growth inhibitory effects on colorectal adenoma cells derived from a patient with FAP, and further research on this combination as promising chemopreventive strategy is desired. -- Highlights: Black-Right-Pointing-Pointer Celecoxib and UDCA acid co-treatment decreases cell growth in colon tumor cells. Black-Right-Pointing-Pointer UDCA enriched 'artificial bile' decreases LT-97 cell growth only in presence of celecoxib. Black-Right-Pointing-Pointer PCNA, caspase-3, nor COX-2 seem to be involved in the observed changes in cell growth.

  16. Celecoxib and tauro-ursodeoxycholic acid co-treatment inhibits cell growth in familial adenomatous polyposis derived LT97 colon adenoma cells

    International Nuclear Information System (INIS)

    Heumen, Bjorn W.H. van; Roelofs, Hennie M.J.; Morsche, René H.M. te; Marian, Brigitte; Nagengast, Fokko M.; Peters, Wilbert H.M.

    2012-01-01

    Chemoprevention would be a desirable strategy to avoid duodenectomy in patients with familial adenomatous polyposis (FAP) suffering from duodenal adenomatosis. We investigated the in vitro effects on cell proliferation, apoptosis, and COX-2 expression of the potential chemopreventives celecoxib and tauro-ursodeoxycholic acid (UDCA). HT-29 colon cancer cells and LT97 colorectal micro-adenoma cells derived from a patient with FAP, were exposed to low dose celecoxib and UDCA alone or in combination with tauro-cholic acid (CA) and tauro-chenodeoxycholic acid (CDCA), mimicking bile of FAP patients treated with UDCA. In HT-29 cells, co-treatment with low dose celecoxib and UDCA resulted in a decreased cell growth (14–17%, p < 0.01). A more pronounced decrease (23–27%, p < 0.01) was observed in LT97 cells. Cell growth of HT-29 cells exposed to ‘artificial bile’ enriched with UDCA, was decreased (p < 0.001), either in the absence or presence of celecoxib. In LT97 cells incubated with ‘artificial bile’ enriched with UDCA, cell growth was decreased only in the presence of celecoxib (p < 0.05). No clear evidence was found for involvement of proliferating cell nuclear antigen, caspase-3, or COX-2 in the cellular processes leading to the observed changes in cell growth. In conclusion, co-treatment with low dose celecoxib and UDCA has growth inhibitory effects on colorectal adenoma cells derived from a patient with FAP, and further research on this combination as promising chemopreventive strategy is desired. -- Highlights: ► Celecoxib and UDCA acid co-treatment decreases cell growth in colon tumor cells. ► UDCA enriched ‘artificial bile’ decreases LT-97 cell growth only in presence of celecoxib. ► PCNA, caspase-3, nor COX-2 seem to be involved in the observed changes in cell growth.

  17. 26 CFR 48.4161(b)-4 - Tax-free sales.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 16 2010-04-01 2010-04-01 true Tax-free sales. 48.4161(b)-4 Section 48.4161(b)-4 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS EXCISE TAXES MANUFACTURERS AND RETAILERS EXCISE TAXES Sporting Goods § 48.4161(b)-4 Tax-free sales. For...

  18. Deep sequencing shows low-level oncogenic hepatitis B virus variants persists post-liver transplant despite potent anti-HBV prophylaxis.

    Science.gov (United States)

    Lau, K C K; Osiowy, C; Giles, E; Lusina, B; van Marle, G; Burak, K W; Coffin, C S

    2018-01-06

    Recent studies suggest that withdrawal of hepatitis B immune globulin (HBIG) and nucleos(t)ide analogues (NA) prophylaxis may be considered in HBV surface antigen (HBsAg)-negative liver transplant (LT) recipients with a low risk of disease recurrence. However, the frequency of occult HBV infection (OBI) and HBV variants after LT in the current era of potent NA therapy is unknown. Twelve LT recipients on prophylaxis were tested in matched plasma and peripheral blood mononuclear cells (PBMCs) for HBV quasispecies by in-house nested PCR and next-generation sequencing of amplicons. HBV covalently closed circular DNA (cccDNA) was detected in Hirt DNA isolated from PBMCs with cccDNA-specific primers and confirmed by nucleic acid hybridization and Sanger sequencing. HBV mRNA in PBMC was detected with reverse-transcriptase nested PCR. In LT recipients on immunosuppressive therapy (10/12 male; median age 57.5 [IQR: 39.8-66.5]; median follow-up post-LT 60 months; 6 pre-LT hepatocellular carcinoma [HCC]), 9 were HBsAg-. HBV DNA was detected in all plasma and PBMC tested; cccDNA and/or mRNA was detected in the PBMC of 10/12 patients. Significant HBV quasispecies diversity (ie 143-2212 nonredundant HBV species) was noted in both sites, and single nucleotide polymorphisms associated with cirrhosis and HCC were detected at varying frequencies. In conclusion, OBI and HBV variants associated with severe liver disease persist in LT recipients on prophylaxis. Although HBV control and cccDNA transcriptional silencing may occur despite immunosuppression, complete virological eradication does not occur in LT recipients with a history of HBV-related end-stage liver disease. © 2018 John Wiley & Sons Ltd.

  19. Peculiar features of thermal emission of GdB4 and GdB6 single crystals

    International Nuclear Information System (INIS)

    Ostrovskij, E.K.; Taran, A.A.; Kovalev, A.V.; Tkachenko, V.F.; Dudnik, E.M.; Matvienko, A.A.

    1990-01-01

    Thermoemission parameters of single crystals (410) GdB 4 and (110) GdB 6 are studied. Work function is calculated by total current. It is stated that work function of GdB 6 within temperature range of 1500-1880 K after 80 h of annealing varies from 2.95 to 3.10 eV practically with the same temperature coefficient as GdB 4 , i.e. 4.1x10 -4 eV/K. It is shown that single crystal gadolinium hexaboride during the high-temperature annealing in the surface region (∼70 mm) is transformed into gadolinium tetraboride. Influence of free air has been first studied on the GdB 4 emissivity which is determined to increase to p=1.3x10 -2 Pa within the range of T=1640-1840 K

  20. Rigid'' skeleton dynamics of Li sub 3 In sub 2 (PO sub 4 ) sub 3 superionic conductor

    Energy Technology Data Exchange (ETDEWEB)

    Naganovsky, Y K; Sigaryov, S E [Inst. of Crystallography, Academy of Sciences, Moscow (USSR)

    1992-01-01

    The effect studied is made by the thermal prehistory of the Li{sub 3}In{sub 2}(PO{sub 4}){sub 3} ceramics on their structural and electrophysical characteristics. Annealing at T>1290 K is shown to result in a monoclinic (HT) and at T<1230 K, rhombohedral (LT) modifications of the crystal structure of Li{sub 3}In{sub 2}(PO{sub 4}){sub 3}. At the same temperature the ionic conductivity ({sigma}) of the HT-modification is found to be higher than that of LT-modification. Annealing of LT-ceramics at {proportional to}985 K leads to a decrease of {sigma} by as much as two order of magnitude seems due to Li{sup +}-ions redistribution in the (In{sub 2}P{sub 3}O{sub 12}){sub 3{infinity}}{sup 3-} skeleton cavities. In the 290-650 K temperature range phase transitions both in LT- and HT-Li{sub 3}In{sub 2}(PO{sub 4}){sub 3} are observed. (orig.).

  1. Immune reconstitution after allogeneic hematopoietic stem cell transplantation in children: a single institution study of 59 patients

    Directory of Open Access Journals (Sweden)

    Hyun O Kim

    2013-01-01

    Full Text Available &lt;b&gt;Purpose:&lt;/b&gt; Lymphocyte subset recovery is an important factor that determines the success of hematopoietic stem cell transplantation (HSCT. Temporal differences in the recovery of lymphocyte subsets and the factors influencing this recovery are important variables that affect a patient's posttransplant immune reconstitution, and therefore require investigation. &lt;b&gt;Methods:&lt;/b&gt; The time taken to achieve lymphocyte subset recovery and the factors influencing this recovery were investigated in 59 children who had undergone HSCT at the Department of Pediatrics, The Catholic University of Korea Seoul St. Mary's Hospital, and who had an uneventful follow-up period of at least 1 year. Analyses were carried out at 3 and 12 months post-transplant. An additional study was performed 1 month post-transplant to evaluate natural killer (NK cell recovery. The impact of preand post-transplant variables, including diagnosis of Epstein-Barr virus (EBV DNAemia posttransplant,on lymphocyte recovery was evaluated. &lt;b&gt;Results:&lt;/b&gt; The lymphocyte subsets recovered in the following order: NK cells, cytotoxic T cells, B cells,and helper T cells. At 1 month post-transplant, acute graft-versus-host disease was found to contribute significantly to the delay of CD16+/56+ cell recovery. Younger patients showed delayed recovery of both CD3+/CD8+ and CD19+ cells. EBV DNAemia had a deleterious impact on the recovery of both CD3+ and CD3+/CD4+ lymphocytes at 1 year post-transplant. &lt;b&gt;Conclusion:&lt;/b&gt; In our pediatric allogeneic HSCT cohort, helper T cells were the last subset to recover. Younger age and EBV DNAemia had a negative impact on the post-transplant recovery of T cells and B cells.

  2. SWAAM-LT: The long-term, sodium/water reaction analysis method computer code

    International Nuclear Information System (INIS)

    Shin, Y.W.; Chung, H.H.; Wiedermann, A.H.; Tanabe, H.

    1993-01-01

    The SWAAM-LT Code, developed for analysis of long-term effects of sodium/water reactions, is discussed. The theoretical formulation of the code is described, including the introduction of system matrices for ease of computer programming as a general system code. Also, some typical results of the code predictions for available large scale tests are presented. Test data for the steam generator design with the cover-gas feature and without the cover-gas feature are available and analyzed. The capabilities and limitations of the code are then discussed in light of the comparison between the code prediction and the test data

  3. Photoluminescence in Pb{sup 2+} activated SrB{sub 4}O{sub 7} and SrB{sub 2}O{sub 4} phosphors

    Energy Technology Data Exchange (ETDEWEB)

    Gawande, A.B., E-mail: gawandeab@gmail.com [Department of Physics, SGB Amravati University, Amravati-444602, Maharashtra (India); Ingle, J.T. [J. D. Institute of Engineering and Technology, Yavatmal, Maharashtra (India); Sonekar, R.P., E-mail: sonekar_rp@yahoo.com [Department of Physics, G.S. College, Khamgaon District, Buldhana, Maharashtra (India); Omanwar, S.K. [Department of Physics, SGB Amravati University, Amravati-444602, Maharashtra (India)

    2014-05-01

    The powder samples of SrB{sub 4}O{sub 7}:Pb{sup 2+} and SrB{sub 2}O{sub 4}:Pb{sup 2+} were prepared by solution combustion synthesis method. The synthesis is based on the exothermic reaction between the fuel (Urea) and Oxidizer (Ammonium nitrate). The synthesized materials were characterized using TG–DTA, powder XRD, SEM and the photoluminescence properties were studied using a Hitachi F-7000 spectrophotometer at room temperature. Both the samples SrB{sub 4}O{sub 7}:Pb{sup 2+} and SrB{sub 2}O{sub 4}:Pb{sup 2+} show broad emission of Pb{sup 2+} respectively at 307 nm and 360 nm (corresponds to {sup 3}P{sub 1} to {sup 1}S{sub 0} transition). The optimum concentrations of Pb{sup 2+} in both the phosphors SrB{sub 4}O{sub 7}:Pb{sup 2+} and SrB{sub 2}O{sub 4}:Pb{sup 2+} were found to be 3 mol% (relative to Sr) and for this concentration the critical transfer distance R{sub 0} were calculated to be 10.21 Å and 12.22 Å respectively. The Stokes shifts were calculated to be respectively 4464 cm{sup −1} and 8454 cm{sup −1}. The emission bands of both the phosphors are in the UV region and the phosphors can be potential candidates for application in UV lamps. - Highlights: • SrB{sub 4}O{sub 7}:Pb{sup 2+} and SrB{sub 2}O{sub 4}:Pb{sup 2+} have been synthesized by Novel solution combustion synthesis technique. • The synthesized materials were characterized using TG–DTA, powder XRD and SEM. • Photoluminescence spectra of synthesized materials showed the characteristic transition in Pb{sup 2+}. • Stokes shift, optimum concentration and critical transfer distance R{sub 0} were determined.

  4. Effect of increased HoxB4 on human megakaryocytic development

    International Nuclear Information System (INIS)

    Zhong, Yiming; Sullenbarger, Brent; Lasky, Larry C.

    2010-01-01

    Research highlights: → HoxB4 overexpression in human TF1 cells increased the expression of CD61 and CD41a. → HoxB4 fusion protein enhanced megakaryocytic development of CD34 + cord blood cells. → Ectopic HoxB4 increased Tpo receptor expression and decreased c-Myb expression. → HoxB4 RNA silencing increased c-Myb expression and decreased Fli-1 expression. -- Abstract: In order to produce clinically useful quantities of platelets ex vivo we may need to firstly enhance early self-renewal of hematopoietic stem cells (HSCs) and/or megakaryocyte (Mk) progenitors. The homeodomain transcription factor HoxB4 has been shown to be an important regulator of stem cell renewal and hematopoiesis; however, its effect on megakaryopoiesis is unclear. In this study, we investigated the effect of HoxB4 overexpression or RNA silencing on megakaryocytic development in the human TF1 progenitor cell line; we then used recombinant tPTD-HoxB4 fusion protein to study the effect of exogenous HoxB4 on megakaryocytic development of human CD34 positively-selected cord blood cells. We found that ectopic HoxB4 in TF1 cells increased the antigen expression of CD61and CD41a, increased the gene expression of thrombopoietin receptor (TpoR), Scl-1, Cyclin D1, Fog-1 and Fli-1 while it decreased c-Myb expression. HoxB4 RNA silencing in TF1 cells decreased the expression of CD61 and CD41a and decreased Fli-1 expression while it increased the expression of c-Myb. Recombinant tPTD-HoxB4 fusion protein increased the percentages and absolute numbers of CD41a and CD61 positive cells during megakaryocytic differentiation of CD34 positively-selected cord blood cells and increased the numbers of colony-forming unit-megakaryocyte (CFU-Mk). Adding tPTD-HoxB4 fusion protein increased the gene expression of TpoR, Cyclin D1, Fog-1 and Fli-1 while it inhibited c-Myb expression. Our data suggest that increased HoxB4 enhanced early megakaryocytic development in human TF1 cells and CD34 positively-selected cord

  5. Effect of increased HoxB4 on human megakaryocytic development

    Energy Technology Data Exchange (ETDEWEB)

    Zhong, Yiming [Department of Pathology, The Ohio State University, Columbus, OH (United States); Program in Molecular, Cellular, and Developmental Biology, The Ohio State University, Columbus, OH (United States); Sullenbarger, Brent [Department of Pathology, The Ohio State University, Columbus, OH (United States); Lasky, Larry C., E-mail: Lasky.4@osu.edu [Department of Pathology, The Ohio State University, Columbus, OH (United States); Program in Molecular, Cellular, and Developmental Biology, The Ohio State University, Columbus, OH (United States)

    2010-07-30

    Research highlights: {yields} HoxB4 overexpression in human TF1 cells increased the expression of CD61 and CD41a. {yields} HoxB4 fusion protein enhanced megakaryocytic development of CD34{sup +} cord blood cells. {yields} Ectopic HoxB4 increased Tpo receptor expression and decreased c-Myb expression. {yields} HoxB4 RNA silencing increased c-Myb expression and decreased Fli-1 expression. -- Abstract: In order to produce clinically useful quantities of platelets ex vivo we may need to firstly enhance early self-renewal of hematopoietic stem cells (HSCs) and/or megakaryocyte (Mk) progenitors. The homeodomain transcription factor HoxB4 has been shown to be an important regulator of stem cell renewal and hematopoiesis; however, its effect on megakaryopoiesis is unclear. In this study, we investigated the effect of HoxB4 overexpression or RNA silencing on megakaryocytic development in the human TF1 progenitor cell line; we then used recombinant tPTD-HoxB4 fusion protein to study the effect of exogenous HoxB4 on megakaryocytic development of human CD34 positively-selected cord blood cells. We found that ectopic HoxB4 in TF1 cells increased the antigen expression of CD61and CD41a, increased the gene expression of thrombopoietin receptor (TpoR), Scl-1, Cyclin D1, Fog-1 and Fli-1 while it decreased c-Myb expression. HoxB4 RNA silencing in TF1 cells decreased the expression of CD61 and CD41a and decreased Fli-1 expression while it increased the expression of c-Myb. Recombinant tPTD-HoxB4 fusion protein increased the percentages and absolute numbers of CD41a and CD61 positive cells during megakaryocytic differentiation of CD34 positively-selected cord blood cells and increased the numbers of colony-forming unit-megakaryocyte (CFU-Mk). Adding tPTD-HoxB4 fusion protein increased the gene expression of TpoR, Cyclin D1, Fog-1 and Fli-1 while it inhibited c-Myb expression. Our data suggest that increased HoxB4 enhanced early megakaryocytic development in human TF1 cells and CD34

  6. CASMO5 JENDL-4.0 and ENDF/B-VII.1beta4 libraries

    International Nuclear Information System (INIS)

    Rhodes, J.; Gheorghiu, N.; Ferrer, R.

    2012-01-01

    This paper details the generation of neutron data libraries for the CASMO5 lattice physics code based on the recently released JENDL-4.0 and ENDF/B-VII.1beta4 nuclear data evaluations. This data represents state-of-the-art nuclear data for late-2011. The key features of the new evaluations are briefly described along with the procedure for processing of this data into CASMO5, 586-energy group neutron data libraries. Finally some CASMO5 results for standard UO 2 and MOX critical experiments for the two new libraries and the current ENDF/B-VII.0 CASMO5 library are presented including the B and W 1810 series, DIMPLE S06A, S06B, TCA reflector criticals with iron plates and the PNL-30-35 MOX criticals. The results show that CASMO5 with the new libraries is performing well for these criticals with a very slight edge in results to the JENDL-4.0 nuclear data evaluation over the ENDF/B-VII.1beta4 evaluation. Work is currently underway to generate a CASMO5 library based on the final ENDF/B-VII.R1 evaluation released Dec. 22, 2011. (authors)

  7. Aspirin-triggered lipoxin A4 and lipoxin A4 up-regulate transcriptional corepressor NAB1 in human neutrophils.

    Science.gov (United States)

    Qiu, F H; Devchand, P R; Wada, K; Serhan, C N

    2001-12-01

    Aspirin-triggered 15-epi-lipoxin A4 (ATL) is an endogenous lipid mediator that mimics the actions of native lipoxin A4, a putative "stop signal" involved in regulating resolution of inflammation. A metabolically more stable analog of ATL, 15-epi-16-(para-fluoro)-phenoxy-lipoxin A4 analog (ATLa), inhibits neutrophil recruitment in vitro and in vivo and displays potent anti-inflammatory actions. ATLa binds with high affinity to the lipoxin A4 receptor, a G protein-coupled receptor on the surface of leukocytes. In this study, we used freshly isolated human neutrophils to examine ATLa's potential for initiating rapid nuclear responses. Using differential display reverse transcription polymerase chain reaction, we identified a subset of genes that was selectively up-regulated upon short exposure of polymorphonuclear leukocytes to ATLa but not to the chemoattractant leukotriene B4 or vehicle alone. We further investigated ATLa regulation of one of the genes, NAB1, a transcriptional corepressor identified previously as a glucocorticoid-responsive gene in hamster smooth muscle cells. Treatment of human neutrophils with pertussis toxin blocked ATLa up-regulation of NAB1. In addition, ATLa stimulated NAB1 gene expression in murine lung vascular smooth muscle in vivo. These findings provide evidence for rapid transcriptional induction of a cassette of genes via an ATLa-stimulated G protein-coupled receptor pathway that is potentially protective and overlaps with the anti-inflammatory glucocorticoid regulatory circuit.

  8. Effects of acrolein on leukotriene biosynthesis in human neutrophils.

    Science.gov (United States)

    Berry, Karin A Zemski; Henson, Peter M; Murphy, Robert C

    2008-12-01

    Acrolein is a toxic, highly reactive alpha,beta-unsaturated aldehyde that is present in high concentrations in cigarette smoke. In the current study, the effect of acrolein on eicosanoid synthesis in stimulated human neutrophils was examined. Eicosanoid synthesis in neutrophils was initiated by priming with granulocyte-macrophage colony-stimulating factor (GM-CSF) and subsequent stimulation with formyl-methionyl-leucyl-phenylalanine (fMLP) and 5-lipoxygenase (5-LO) products in addition to small amounts of cyclooxygenase (COX) products were detected using LC/MS/MS. A dose-dependent decrease in the formation of 5-LO products was observed in GM-CSF/fMLP-stimulated neutrophils when acrolein (0-50 microM) was present with almost complete inhibition at > or = 25 microM acrolein. The production of COX products was not affected by acrolein in these cells. The effect of acrolein was examined on key parts of the eicosanoid pathway, such as arachidonic acid release, intracellular calcium ion concentration, and adenosine production. In addition, the direct effect of acrolein on 5-LO enzymatic activity was probed using a recombinant enzyme. Some of these factors were affected by acrolein but did not completely explain the almost complete inhibition of 5-LO product formation in GM-CSF/fMLP-treated cells with acrolein. In addition, the effect of acrolein on different stimuli that initiate the 5-LO pathway [platelet-activating factor (PAF)/fMLP, GM-CSF/PAF, opsonized zymosan, and A23187] was examined. Acrolein had no significant effect on the leukotriene production in neutrophils stimulated with PAF/fMLP, GM-CSF/ PAF, or OPZ. Additionally, 50% inhibition of the 5-LO pathway was observed in A23187-stimulated neutrophils. Our results suggest that acrolein has a profound effect on the 5-LO pathway in neutrophils, which may have implications in disease states, such as chronic obstructive pulmonary disease and other pulmonary disease, where both activated neutrophils and acrolein are

  9. Photoelectron spectroscopy of B4O4-: Dual 3c-4e π hyperbonds and rhombic 4c-4e o-bond in boron oxide clusters

    Science.gov (United States)

    Tian, Wen-Juan; Zhao, Li-Juan; Chen, Qiang; Ou, Ting; Xu, Hong-Guang; Zheng, Wei-Jun; Zhai, Hua-Jin; Li, Si-Dian

    2015-04-01

    Gas-phase anion photoelectron spectroscopy (PES) is combined with global structural searches and electronic structure calculations at the hybrid Becke 3-parameter exchange functional and Lee-Yang-Parr correlation functional (B3LYP) and single-point coupled-cluster with single, double, and perturbative triple excitations (CCSD(T)) levels to probe the structural and electronic properties and chemical bonding of the B4O40/- clusters. The measured PES spectra of B4O4- exhibit a major band with the adiabatic and vertical detachment energies (ADE and VDE) of 2.64 ± 0.10 and 2.81 ± 0.10 eV, respectively, as well as a weak peak with the ADE and VDE of 1.42 ± 0.08 and 1.48 ± 0.08 eV. The former band proves to correspond to the Y-shaped global minimum of Cs B4O4- (2A″), with the calculated ADE/VDE of 2.57/2.84 eV at the CCSD(T) level, whereas the weak band is associated with the second lowest-energy, rhombic isomer of D2h B4O4- (2B2g) with the predicted ADE/VDE of 1.43/1.49 eV. Both anion structures are planar, featuring a B atom or a B2O2 core bonded with terminal BO and/or BO2 groups. The same Y-shaped and rhombic structures are also located for the B4O4 neutral cluster, albeit with a reversed energy order. Bonding analyses reveal dual three-center four-electron (3c-4e) π hyperbonds in the Y-shaped B4O40/- clusters and a four-center four-electron (4c-4e) π bond, that is, the so-called o-bond in the rhombic B4O40/- clusters. This work is the first experimental study on a molecular system with an o-bond.

  10. B7-2 Expressed on EL4 Lymphoma Suppresses Antitumor Immunity by an Interleukin 4–dependent Mechanism

    Science.gov (United States)

    Stremmel, C.; Greenfield, E.A.; Howard, E.; Freeman, G.J.; Kuchroo, V.K.

    1999-01-01

    For T cells to become functionally activated they require at least two signals. The B7 costimulatory molecules B7-1 and B7-2 provide the “second signal” pivotal for T cell activation. In this report, we studied the relative roles of B7-1 and B7-2 molecules in the induction of antitumor immunity to the T cell thymoma, EL4. We generated EL4 tumor cells that expressed B7-1, B7-2, and B7-1+B7-2 by transfecting murine cDNAs. Our results demonstrate that EL4B7-1 cells are completely rejected in syngeneic mice. Unlike EL4B7-1 cells, we find that EL4B7-2 cells are not rejected but progressively grow in the mice. A B7-1– and B7-2–EL4 double transfectant was generated by introducing B7-2 cDNA into the EL4B7-1 tumor line that regressed in vivo. The EL4B7-1+B7-2 double transfectant was not rejected when implanted into syngeneic mice but progressively grew to produce tumors. The double transfectant EL4 cells could costimulate T cell proliferation that could be blocked by anti–B7-1 antibodies, anti–B7-2 antibodies, or hCTLA4 immunoglobulin, showing that the B7-1 and B7-2 molecules expressed on the EL4 cells were functional. In vivo, treatment of mice implanted with double-transfected EL4 cells with anti–B7-2 monoclonal antibody resulted in tumor rejection. Furthermore, the EL4B7-2 and EL4B7-1+B7-2 cells, but not the wild-type EL4 cells, were rejected in interleukin 4 (IL-4) knockout mice. Our data suggests that B7-2 expressed on some T cell tumors inhibits development of antitumor immunity, and IL-4 appears to play a critical role in abrogation of the antitumor immune response. PMID:10075975

  11. Effekten af hydraulisk kontrol på den vertikale fordeling og sammensætning af fytoplankton og zooplanktonsamfundene i Lillebælt

    DEFF Research Database (Denmark)

    Nielsen, Erik Haar; Christensen, Jens Tang; Lund-Hansen, Lars Chresten

    Effekten af strømbetinget opblanding på fytoplankton og zooplankton sammensætningen i en lagdelt vandsøjle blev undersøgt i Lillebælt i april 2015. De hydrografiske forhold blev kortlagt gennem kontinuerlige målinger med ADCP og undulerende CTD (Scanfish III) langs et transekt fra Tragten nord...... for Fredericia til det centrale Lillebælt. Vandprøver til analyse af fytoplankton blev taget fra tre strata med CTD forsynet med en rosette med Niskin -vandhentere og zooplankton blev indsamlet med et Multinet-maxi (HydroBios, Kiel) fra 9 strata i vandsøjlen. Under kraftig sydgående strøm viste hydrografien...

  12. Fra SK 4b til MH 17

    DEFF Research Database (Denmark)

    Stræde, Therkel

    2015-01-01

    Om den nazistiske besættelsespolitik i Sydøstukraine og Sonderkommando 4b's udryddelse af jøder på den egn, hvor Malaysian Airlines MH 17 styrtede ned den 17. juli 2014......Om den nazistiske besættelsespolitik i Sydøstukraine og Sonderkommando 4b's udryddelse af jøder på den egn, hvor Malaysian Airlines MH 17 styrtede ned den 17. juli 2014...

  13. WARM SPITZER OBSERVATIONS OF THREE HOT EXOPLANETS: XO-4b, HAT-P-6b, AND HAT-P-8b

    Energy Technology Data Exchange (ETDEWEB)

    Todorov, Kamen O. [Department of Astronomy and Astrophysics, The Pennsylvania State University, University Park, PA 16802 (United States); Deming, Drake [Planetary Systems Laboratory, NASA' s Goddard Space Flight Center, Greenbelt, MD 20771 (United States); Knutson, Heather A. [Division of Geological and Planetary Sciences, California Institute of Technology, Pasadena, CA 91125 (United States); Burrows, Adam [Department of Astrophysical Sciences, Princeton University, Princeton, NJ 05844 (United States); Sada, Pedro V. [Department of Physics and Mathematics, University of Monterrey, Monterrey (Mexico); Cowan, Nicolas B. [Department of Physics and Astronomy, Northwestern University, Evanston, IL 60208 (United States); Agol, Eric [Department of Astronomy, University of Washington, Box 351580, Seattle, WA 98195 (United States); Desert, Jean-Michel; Charbonneau, David [Harvard-Smithsonian Center for Astrophysics, Cambridge, MA 02138 (United States); Fortney, Jonathan J.; Laughlin, Gregory [Department of Astronomy and Astrophysics, University of California at Santa Cruz, Santa Cruz, CA 95064 (United States); Langton, Jonathan [Department of Physics, Principia College, Elsah, IL 62028 (United States); Showman, Adam P.; Lewis, Nikole K. [Lunar and Planetary Laboratory, University of Arizona, Tucson, AZ 85721 (United States)

    2012-02-10

    We analyze Warm Spitzer/Infrared Array Camera observations of the secondary eclipses of three planets, XO-4b, HAT-P-6b, and HAT-P-8b. We measure secondary eclipse amplitudes at 3.6 {mu}m and 4.5 {mu}m for each target. XO-4b exhibits a stronger eclipse depth at 4.5 {mu}m than at 3.6 {mu}m, which is consistent with the presence of a temperature inversion. HAT-P-8b shows a stronger eclipse amplitude at 3.6 {mu}m and is best described by models without a temperature inversion. The eclipse depths of HAT-P-6b can be fitted with models with a small or no temperature inversion. We consider our results in the context of a postulated relationship between stellar activity and temperature inversion and a relationship between irradiation level and planet dayside temperature, as discussed by Knutson et al. and Cowan and Agol, respectively. Our results are consistent with these hypotheses, but do not significantly strengthen them. To measure accurate secondary eclipse central phases, we require accurate ephemerides. We obtain primary transit observations and supplement them with publicly available observations to update the orbital ephemerides of the three planets. Based on the secondary eclipse timing, we set upper boundaries for ecos ({omega}) for HAT-P-6b, HAT-P-8b, and XO-4b and find that the values are consistent with circular orbits.

  14. Mutagenicity, stable DNA adducts, and abasic sites induced in Salmonella by phenanthro[3,4-b]- and phenanthro[4,3-b]thiophenes, sulfur analogs of benzo[c]phenanthrene

    Energy Technology Data Exchange (ETDEWEB)

    Swartz, Carol D. [Department of Environmental Science and Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States); King, Leon C.; Nesnow, Stephen [Environmental Carcinogenesis Division, US Environmental Protection Agency, Research Triangle Park, NC, 27711 (United States); Umbach, David M. [Biostatistics Branch, National Institute of Environmental Health Sciences, National Institutes of Health, DHHS, Research Triangle Park, NC 27709 (United States); Kumar, Subodh [Environmental Toxicology and Chemistry Laboratory, Great Lakes Center, State University of New York College at Buffalo, Buffalo, NY 14222 (United States); DeMarini, David M. [Environmental Carcinogenesis Division, US Environmental Protection Agency, Research Triangle Park, NC, 27711 (United States)], E-mail: demarini.david@epa.gov

    2009-02-10

    Sulfur-containing polycyclic aromatic hydrocarbons (thia-PAHs or thiaarenes) are common constituents of air pollution and cigarette smoke, but only a few have been studied for health effects. We evaluated the mutagenicity in Salmonella TA98, TA100, and TA104 of two sulfur-containing derivatives of benzo[c]phenanthrene, phenanthro[3,4-b]thiophene (P[3,4-b]T), and phenanthro[4,3-b]thiophene (P[4,3-b]T) as well as their dihydrodiol and sulfone derivatives. In addition, we assessed levels of stable DNA adducts (by {sup 32}P-postlabeling) as well as abasic sites (by an aldehydic-site assay) produced by six of these compounds in TA100. P[3,4-b]T and its 6,7- and 8,9-diols, P[3,4-b]T sulfone, P[4,3-b]T, and its 8,9-diol were mutagenic in TA100. P[3,4-b]T sulfone, the most potent mutagen, was approximately twice as potent as benzo[a]pyrene in both TA98 and TA100. Benzo-ring dihydrodiols were much more potent than K-region dihydrodiols, which had little or no mutagenic activity in any strain. P[3,4-b]T sulfone produced abasic sites and not stable DNA adducts; the other five compounds examined, B[c]P, B[c]P 3,4-diol, P[3,4-b]T, P[3,4-b]T 8,9-diol, and P[4,3-b]T 8,9-diol, produced only stable DNA adducts. P[3,4-b]T sulfone was the only compound that produced significant levels of frameshift mutagenicity and induced mutations primarily at GC sites. In contrast, B[c]P, its 3,4-diol, and the 8,9 diols of the phenanthrothiophenes induced mutations primarily at AT sites. P[3,4-b]T was not mutagenic in TA104, whereas P[3,4-b]T sulfone was. The two isomeric forms (P[3,4-b]T and P[4,3-b]T) are apparently activated differently, with the latter, but not the former, involving a diol pathway. This study is the first illustrating the potential importance of abasic sites in the mutagenicity of thia-PAHs.

  15. A SEARCH FOR L/T TRANSITION DWARFS WITH Pan-STARRS1 AND WISE: DISCOVERY OF SEVEN NEARBY OBJECTS INCLUDING TWO CANDIDATE SPECTROSCOPIC VARIABLES

    International Nuclear Information System (INIS)

    Best, William M. J.; Liu, Michael C.; Magnier, Eugene A.; Aller, Kimberly M.; Burgett, W. S.; Chambers, K. C.; Hodapp, K. W.; Kaiser, N.; Kudritzki, R.-P.; Morgan, J. S.; Tonry, J. L.; Wainscoat, R. J.; Deacon, Niall R.; Dupuy, Trent J.; Redstone, Joshua; Price, P. A.

    2013-01-01

    We present initial results from a wide-field (30,000 deg 2 ) search for L/T transition brown dwarfs within 25 pc using the Pan-STARRS1 and Wide-field Infrared Survey Explorer (WISE) surveys. Previous large-area searches have been incomplete for L/T transition dwarfs, because these objects are faint in optical bands and have near-infrared (near-IR) colors that are difficult to distinguish from background stars. To overcome these obstacles, we have cross-matched the Pan-STARRS1 (optical) and WISE (mid-IR) catalogs to produce a unique multi-wavelength database for finding ultracool dwarfs. As part of our initial discoveries, we have identified seven brown dwarfs in the L/T transition within 9-15 pc of the Sun. The L9.5 dwarf PSO J140.2308+45.6487 and the T1.5 dwarf PSO J307.6784+07.8263 (both independently discovered by Mace et al.) show possible spectroscopic variability at the Y and J bands. Two more objects in our sample show evidence of photometric J-band variability, and two others are candidate unresolved binaries based on their spectra. We expect our full search to yield a well-defined, volume-limited sample of L/T transition dwarfs that will include many new targets for study of this complex regime. PSO J307.6784+07.8263 in particular may be an excellent candidate for in-depth study of variability, given its brightness (J = 14.2 mag) and proximity (11 pc)

  16. Clinical features and surgical outcomes of complete transposition of the great arteries

    Directory of Open Access Journals (Sweden)

    Suk Jin Hong

    2012-10-01

    Full Text Available &lt;B&gt;Purpose:&lt;/B&gt; This single-center study aimed to assess the clinical features and surgical approaches and outcomes of complete transposition of the great arteries (TGA. &lt;B&gt;Methods:&lt;/B&gt; TGA patients who had undergone surgical correction at the Kyungpook National University Hospital from January 2000 to December 2010, were retrospectively evaluated for patient characteristics, clinical manifestation, preoperative management, intraoperative findings, postoperative progress, and follow-up status. &lt;B&gt;Results:&lt;/B&gt; Twenty-eight patients (17 boys and 11 girls, mean age= 10.6±21.5 days were included and were categorized as follows: group I, TGA with intact ventricular septum (n=13; group II, TGA with ventricular septal defect (VSD, n=12; and group III, TGA/VSD with pulmonary stenosis (n=3. Group I underwent the most intensive preoperative management (balloon atrial septostomy and prostaglandin E1 medication. Group II showed the highest incidence of heart failure (P&lt;0.05. Usual and unusual coronary anatomy patterns were observed in 20 (71% and 8 patients, respectively. Arterial and half-turned truncal switch operations were performed in 25 and 3 patients (Group III, respectively. Postoperative complications included cardiac arrhythmias (8 patients, central nervous system complications (3 patients, acute renal failure (1 patient, infections (3 patients, and cardiac tamponade (1 patient, and no statistically significant difference was observed between the groups. Group II showed the mildest aortic regurgitation on follow-up echocardiograms (P&lt;0.05. One patient underwent reoperation, and 1 died. The overall mortality rate was 4%. &lt;B&gt;Conclusion:&lt;/B&gt; Our study showed favorable results in all the groups and no significant difference in postoperative complication, reoperation, and mortality among the groups. However, our results were

  17. Intradermal delivery of Shigella IpaB and IpaD type III secretion proteins: kinetics of cell recruitment and antigen uptake, mucosal and systemic immunity, and protection across serotypes.

    Science.gov (United States)

    Heine, Shannon J; Diaz-McNair, Jovita; Andar, Abhay U; Drachenberg, Cinthia B; van de Verg, Lillian; Walker, Richard; Picking, Wendy L; Pasetti, Marcela F

    2014-02-15

    Shigella is one of the leading pathogens contributing to the vast pediatric diarrheal disease burden in low-income countries. No licensed vaccine is available, and the existing candidates are only partially effective and serotype specific. Shigella type III secretion system proteins IpaB and IpaD, which are conserved across Shigella spp., are candidates for a broadly protective, subunit-based vaccine. In this study, we investigated the immunogenicity and protective efficacy of IpaB and IpaD administered intradermally (i.d.) with a double-mutant of the Escherichia coli heat-labile enterotoxin (dmLT) adjuvant using microneedles. Different dosage levels of IpaB and IpaD, with or without dmLT, were tested in mice. Vaccine delivery into the dermis, recruitment of neutrophils, macrophages, dendritic cells, and Langerhans cells, and colocalization of vaccine Ag within skin-activated APC were demonstrated through histology and immunofluorescence microscopy. Ag-loaded neutrophils, macrophages, dendritic cells, and Langerhans cells remained in the tissue at least 1 wk. IpaB, IpaD, and dmLT-specific serum IgG- and IgG-secreting cells were produced following i.d. immunization. The protective efficacy was 70% against Shigella flexneri and 50% against Shigella sonnei. Similar results were obtained when the vaccine was administered intranasally, with the i.d. route requiring 25-40 times lower doses. Distinctively, IgG was detected in mucosal secretions; secretory IgA, as well as mucosal and systemic IgA Ab-secreting cells, were seemingly absent. Vaccine-induced T cells produced IFN-γ, IL-2, TNF-α, IL-17, IL-4, IL-5, and IL-10. These results demonstrate the potential of i.d. vaccination with IpaB and IpaD to prevent Shigella infection and support further studies in humans.

  18. Magnetic fluctuations in UNi4B

    DEFF Research Database (Denmark)

    Mentink, S.A.M.; Mason, T.E.; Buyers, W.J.L.

    1997-01-01

    We investigate the magnetic fluctuation spectrum of the geometrically frustrated antiferromagnetic compound UNi4B, which partially orders below T-N = 20 K. An overdamped spin excitation is observed at the AF wave vector around 2.4 meV. Low-frequency, weakly Q-dependent inelastic scattering...

  19. Real-time PCR quantification of human complement C4A and C4B genes

    Directory of Open Access Journals (Sweden)

    Fust George

    2006-01-01

    Full Text Available Abstract Background The fourth component of human complement (C4, an essential factor of the innate immunity, is represented as two isoforms (C4A and C4B in the genome. Although these genes differ only in 5 nucleotides, the encoded C4A and C4B proteins are functionally different. Based on phenotypic determination, unbalanced production of C4A and C4B is associated with several diseases, such as systemic lupus erythematosus, type 1 diabetes, several autoimmune diseases, moreover with higher morbidity and mortality of myocardial infarction and increased susceptibility for bacterial infections. Despite of this major clinical relevance, only low throughput, time and labor intensive methods have been used so far for the quantification of C4A and C4B genes. Results A novel quantitative real-time PCR (qPCR technique was developed for rapid and accurate quantification of the C4A and C4B genes applying a duplex, TaqMan based methodology. The reliable, single-step analysis provides the determination of the copy number of the C4A and C4B genes applying a wide range of DNA template concentration (0.3–300 ng genomic DNA. The developed qPCR was applied to determine C4A and C4B gene dosages in a healthy Hungarian population (N = 118. The obtained data were compared to the results of an earlier study of the same population. Moreover a set of 33 samples were analyzed by two independent methods. No significant difference was observed between the gene dosages determined by the employed techniques demonstrating the reliability of the novel qPCR methodology. A Microsoft Excel worksheet and a DOS executable are also provided for simple and automated evaluation of the measured data. Conclusion This report describes a novel real-time PCR method for single-step quantification of C4A and C4B genes. The developed technique could facilitate studies investigating disease association of different C4 isotypes.

  20. Effect of subclinical hypothyroidism on the skeletal system and improvement with short-term thyroxine therapy.

    Science.gov (United States)

    Gao, Cuixia; Wang, Yu; Li, Tingting; Huang, Jing; Tian, Limin

    2017-10-27

    The purpose of the study was to observe changes in the skeletal system of rats with subclinical hypothyroidism (SCH) and to determine whether L-thyroxine (L-T4) administration suppresses those changes. Sixty male Wistar rats were randomly divided into control, SCH, and SCH+T4 groups. SCH was induced in rats by administration of methimazole (MMI), and rats in the SCH+T4 group were treated with L-T4 after 45 days of MMI administration. The SCH group had higher thyroid-stimulating hormone (TSH) level than the control and SCH+T4 groups. There were no differences in serum thyroid hormone (FT4 and FT3) levels among the three groups. Bone mineral density; serum levels of BALP and TRACP-5b, two bone metabolic markers; and the biomechanical properties of the femurs were lower in the SCH group than in the control group. After L-T4 treatment, serum BALP and TRACP-5b levels and the femur biomechanical properties were higher in the SCH+T4 than the SCH group. Histopathological examination revealed damage to the structure of the femur trabecular bone network in rats with SCH, and L-T4 treatment improved this condition to some extent. These findings demonstrate that L-T4 treatment ameliorates the destructive effects of SCH on the skeletal system in rats.

  1. Photoelectron spectroscopy of B4O4−: Dual 3c-4e π hyperbonds and rhombic 4c-4e o-bond in boron oxide clusters

    International Nuclear Information System (INIS)

    Tian, Wen-Juan; Chen, Qiang; Ou, Ting; Li, Si-Dian; Zhao, Li-Juan; Xu, Hong-Guang; Zheng, Wei-Jun; Zhai, Hua-Jin

    2015-01-01

    Gas-phase anion photoelectron spectroscopy (PES) is combined with global structural searches and electronic structure calculations at the hybrid Becke 3-parameter exchange functional and Lee-Yang-Parr correlation functional (B3LYP) and single-point coupled-cluster with single, double, and perturbative triple excitations (CCSD(T)) levels to probe the structural and electronic properties and chemical bonding of the B 4 O 4 0/− clusters. The measured PES spectra of B 4 O 4 − exhibit a major band with the adiabatic and vertical detachment energies (ADE and VDE) of 2.64 ± 0.10 and 2.81 ± 0.10 eV, respectively, as well as a weak peak with the ADE and VDE of 1.42 ± 0.08 and 1.48 ± 0.08 eV. The former band proves to correspond to the Y-shaped global minimum of C s B 4 O 4 − ( 2 A″), with the calculated ADE/VDE of 2.57/2.84 eV at the CCSD(T) level, whereas the weak band is associated with the second lowest-energy, rhombic isomer of D 2h B 4 O 4 − ( 2 B 2g ) with the predicted ADE/VDE of 1.43/1.49 eV. Both anion structures are planar, featuring a B atom or a B 2 O 2 core bonded with terminal BO and/or BO 2 groups. The same Y-shaped and rhombic structures are also located for the B 4 O 4 neutral cluster, albeit with a reversed energy order. Bonding analyses reveal dual three-center four-electron (3c-4e) π hyperbonds in the Y-shaped B 4 O 4 0/− clusters and a four-center four-electron (4c-4e) π bond, that is, the so-called o-bond in the rhombic B 4 O 4 0/− clusters. This work is the first experimental study on a molecular system with an o-bond

  2. Incorporating isolated molybdenum (Mo) atoms into Bilayer Epitaxial Graphene on 4H-SiC(0001)

    Science.gov (United States)

    Huang, Han; Wan, Wen; Li, Hui; Wong, Swee Liang; Lv, Lu; Gao, Yongli; Wee, Andrew T. S.

    2014-03-01

    The atomic structures and electronic properties of isolated Mo atoms in bilayer epitaxial graphene (BLEG) on 4H-SiC(0001) are investigated by low temperature scanning tunneling microscopy (LT-STM). LT-STM results reveal that isolated Mo dopants prefer to substitute C atoms at α-sites, and preferentially locate between the graphene bilayers. First-principles calculations confirm that the embedding of single Mo dopants within BLEG is energetically favorable as compared to monolayer graphene. The calculated bandstructures show that Mo-doped BLEG is n-doped, and each Mo atom introduces a local magnetic moment of 1.81 μB. Our findings demonstrate a simple and stable method to incorporate single transition metal dopants into the graphene lattice to tune its electronic and magnetic properties for possible use in graphene spin devices. NRF-CRP (Singapore) grants R-143-000-360-281and R-144-000-295-281. ``Shenghua Professorship'' startup funding from CSU and the support from the NSF of China (Grant No.11304398).

  3. Phorbol 12-myristate 13-acetate enhances nm23 gene expression in murine melanocytes but not in syngeneic B16-BL6 melanoma variants.

    Science.gov (United States)

    Huijzer, J C; McFarland, M; Niles, R M; Meadows, G G

    1996-03-01

    The nm23 gene has been described as a potential metastasis suppressor gene in certain rodent and human tumors. We previously demonstrated that tyrosine and phenylalanine restriction suppresses metastatic heterogeneity of B16-BL6 murine melanoma and selects for tumor variants with decreased metastatic potential. In this study, we investigated nm23 expression in the highly metastatic B16-BL6 (ND) melanoma, its nutritionally derived poorly metastatic (LT) variant, and the syngeneic non-tumorigenic Mel-ab melanocytes. No differences in nm23 expression were observed between ND and LT cells, and nm23 expression varied between different isolates. Previously, we showed that metastatic potential of 1-ND cells decreases and is not altered in 1-LT cells after prolonged in vitro cell passage; however, nm23 expression is equivalently increased by 2-fold. In 2-ND and 2-LT cells, expression of nm23 is not different at higher in vitro cell passage. Expression of nm23 decreased about 2-fold when phorbol 12-myristate 13-acetate (PMA) was removed from Mel-ab cells, which induces these cells to become quiescent. Although membrane-associated protein kinase C (PKC) activity decreased after prolonged PMA treatment in all cells, neither nm23 expression nor proliferation of ND and LT cells was affected by PMA. These data indicate that nm23 expression is related to proliferative activity rather than to the suppression of metastatic potential.

  4. (4bS,8aS-1-Isopropyl-4b,8,8-trimethyl-4b,5,6,7,8,8a,9,10-octahydrophenanthren-2-yl acetate

    Directory of Open Access Journals (Sweden)

    Radouane Oubabi

    2014-03-01

    Full Text Available The hemisynthesis of the title compound, C22H32O2, was carried out through direct acetylation reaction of the naturally occurring diterpene totarol [systematic name: (4bS,8aS-4b,8,8-trimethyl-1-propan-2-yl-5,6,7,8a,9,10-hexahydrophenanthren-2-ol]. The molecule is built up from three fused six membered rings, one saturated and two unsaturated. The central unsaturated ring has a half-chair conformation, whereas the other unsaturated ring displays a chair conformation. The absolute configuration is deduced from the chemical pathway. The value of the Hooft parameter [−0.10 (6] allowed this absolute configuration to be confirmed.

  5. Quantum oscillation measurements of β-LuAlB{sub 4}

    Energy Technology Data Exchange (ETDEWEB)

    Reiss, Pascal; Baglo, Jordan; Chen, Xiaoye; Tan, HongEn; Sutherland, Michael; Grosche, F. Malte [Cavendish Laboratory, University of Cambridge, Cambridge (United Kingdom); Friedemann, Sven [HH Wills Laboratory, University of Bristol, Bristol (United Kingdom); Goh, Swee K. [Chinese University of Hong Kong, Shatin, N.T. (China); Kuga, Kentaro; Nakatsuji, Satoru [Institute for Solid State Physics, University of Tokyo, Kashiwa (Japan); Harima, Hisatomo [Department of Physics, Graduate School of Science, Kobe University, Kobe (Japan)

    2016-07-01

    The Yb-based heavy fermion superconductor β-YbAlB{sub 4} displays a quantum critical point without tuning by applied pressure, magnetic field, or doping, which has been attributed to an unusual renormalised band structure. Quantum oscillation measurements of the Fermi surface in β-YbAlB{sub 4} have so far proved inconclusive, motivating us to undertake a detailed study of the isostructural reference compound β-LuAlB{sub 4}, which in contrast to the Yb compound is characterised by a filled 4f shell. We present comprehensive results from rotation and mass studies in β-LuAlB{sub 4}, which broadly agree with band structure calculations and display moderate mass enhancements contrasting with the much larger enhancements seen in β-YbAlB{sub 4} - further emphasising the important contribution of f electrons to the itinerant electron physics of β-YbAlB{sub 4}.

  6. Tetrahedral 1B4Sb nanoclusters in GaP:(B, Sb)

    Energy Technology Data Exchange (ETDEWEB)

    Elyukhin, V A, E-mail: elyukhin@cinvestav.m [Departamento de Ingenieria Electrica-SEES, CINVESTAV-IPN, Avenida IPN 2508, Col. San Pedro Zacatenco, C. P. 07360, Mexico, D. F. (Mexico)

    2009-05-01

    Self-assembling conditions of 1B4Sb tetrahedral nanoclusters in GaP doped with boron and Sb isoelectronic impurities are represented in the ultradilute and dilute limits of the boron and Sb contents, respectively. The fulfilled estimates demonstrated the preferential complete or almost complete allocation of boron atoms in 1B4Sb nanoclusters at temperatures of 500 {sup 0}C and 900 {sup 0}C, respectively. The significant decrease of the sum of the free energies of the constituent compounds is the main origin of self-assembling. The reduction of the strain energy is the additional cause of this phenomenon.

  7. Modulation of Polymorphonuclear Neutrophil Response to N-formyl-l-methionyl-l-leucyl-l-phenylalanine

    Science.gov (United States)

    1988-11-10

    acid. This paradox remains · unresolved, but it is attractive to postulate that circumstances exist where PMNs release potent mediators such as LTB 4...Panel A represents 1· n.YI A2318i pretreatment.. panel B ’I ::· ,. r epre ~ent s 10 n\\1 A2318i pretreatment and panel C represents 100 n\\I : t... Paradox : Neutrophile Can, But Will Not, Respond to Ligand-Receptor Interactions by Forming Leukotriene B4 or it Metab olites. Biochem. J., 241:55

  8. Impairment of Neutrophil Migration to Remote Inflammatory Site during Lung Histoplasmosis

    Directory of Open Access Journals (Sweden)

    Alexandra I. Medeiros

    2015-01-01

    Full Text Available Histoplasma capsulatum (Hc induces a pulmonary disease in which leukotrienes promote activation and recruitment of effectors cells. It is also well-recognized that leukotriene B4 (LTB4 and platelet-activating factor (PAF induce leukocyte recruitment to inflammatory sites. We investigated the impact of pulmonary Hc infection on PMN migration to a remote inflammatory site. Our results show that pulmonary Hc infection impairs LTB4- or PAF-stimulated PMN recruitment to air pouch. Yet, remote inflammation did not modify PMN numbers in the bronchoalveolar lavage fluid (BALF of Hc-infected mice. Interestingly, the concomitant administration of PAF and LTB4 receptor antagonists inhibited PMN recruitment to both BALF and the remote site, demonstrating cooperation between both mediators. Along that line, our results show that PAF-elicited PMN chemotaxis was abrogated in 5-lipoxygenase-deficient animals. These results suggest caution in the indiscriminate use of anti-inflammatory drugs during infectious diseases.

  9. Ligand stimulation of ErbB4 and a constitutively-active ErbB4 mutant result in different biological responses in human pancreatic tumor cell lines

    International Nuclear Information System (INIS)

    Mill, Christopher P.; Gettinger, Kathleen L.; Riese, David J.

    2011-01-01

    Pancreatic cancer is the fourth leading cause of cancer death in the United States. Indeed, it has been estimated that 37,000 Americans will die from this disease in 2010. Late diagnosis, chemoresistance, and radioresistance of these tumors are major reasons for poor patient outcome, spurring the search for pancreatic cancer early diagnostic and therapeutic targets. ErbB4 (HER4) is a member of the ErbB family of receptor tyrosine kinases (RTKs), a family that also includes the Epidermal Growth Factor Receptor (EGFR/ErbB1/HER1), Neu/ErbB2/HER2, and ErbB3/HER3. These RTKs play central roles in many human malignancies by regulating cell proliferation, survival, differentiation, invasiveness, motility, and apoptosis. In this report we demonstrate that human pancreatic tumor cell lines exhibit minimal ErbB4 expression; in contrast, these cell lines exhibit varied and in some cases abundant expression and basal tyrosine phosphorylation of EGFR, ErbB2, and ErbB3. Expression of a constitutively-dimerized and -active ErbB4 mutant inhibits clonogenic proliferation of CaPan-1, HPAC, MIA PaCa-2, and PANC-1 pancreatic tumor cell lines. In contrast, expression of wild-type ErbB4 in pancreatic tumor cell lines potentiates stimulation of anchorage-independent colony formation by the ErbB4 ligand Neuregulin 1β. These results illustrate the multiple roles that ErbB4 may be playing in pancreatic tumorigenesis and tumor progression.

  10. Differential Features of Cerebral Perfusion in Dementia with Lewy Bodies Compared to Alzheimer's Dementia using SPM Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Do Young; Park, Kyung Won; Kim, Jae Woo [College of Medicine, Univ. of Donga, Busan (Korea, Republic of)

    2003-07-01

    Alzheimer's dementia (AD) and dementia with Lewy bodies (DLB) are most common cause of dementia in elderly people. Clinical distinction in some cases of DLB from AD may be difficult as symptom profiles overlap. Some neuropathologic overlap is also seen as beta-amyloidosis and senile plaques can be found in both disease. Both disease also share severe acetylcholine depletion. We evaluated the differences of brain perfusion between DLB and AD using statistical parametric mapping analysis. Twelve DLB (mean age ; 68.8{+-}8.3 years, K-MMSE ; 17.3{+-}6.1) and 51 AD patients (mean age ; 71.4{+-}7.2 years, K-MMSE ; 16.7{+-}4.5), which were matched for age and severity of dementia, participated in this study. Tc-99m HMPAO SPECT was performed for measuring regional cerebral blood flow. Statistical parametric mapping (SPM99) software was used for automatic and objective approach to analyze SPECT image data. The SPECT data of the patients with DLB were compared to patients with AD. Comparison of the two dementia groups (uncorrected p<0.01) revealed significant hypoperfusion in both occipital (both middle occipital gyrus, Rt B no. 18 and Lt cuneus), both parietal (Lt parietal precuneus, Lt B no. 39, Lt inferior parietal lobule and Rt supramarginal gyrus) lobes in DLB compared with AD. Significant hyperperfusion was noted in Rt frontal (sup. frontal gyrus, B no.10, middle frontal gyrus, B no. 9, B no. 11, inf. frontal gyrus), Rt putamen, Lt ant. cingulate gyrus (B no. 24), both cerebellar post. lobe (Lt tuber, Lt declive, Lt tonsil, Rt declive) in DLB compared with AD. We found a significant differences in the cerebral perfusion pattern between DLB and AD. Differential feature of cerebral perfusion in DLB was both occipital hypoperfusion and preserved Rt frontal perfusion compared to AD. Therefore in difficult case of clinical an neuro pathologic diagnosis, brain perfusion SPECT with SPM analysis may be helpful to differentiate DLB from AD.

  11. Differential Features of Cerebral Perfusion in Dementia with Lewy Bodies Compared to Alzheimer's Dementia using SPM Analysis

    International Nuclear Information System (INIS)

    Kang, Do Young; Park, Kyung Won; Kim, Jae Woo

    2003-01-01

    Alzheimer's dementia (AD) and dementia with Lewy bodies (DLB) are most common cause of dementia in elderly people. Clinical distinction in some cases of DLB from AD may be difficult as symptom profiles overlap. Some neuropathologic overlap is also seen as beta-amyloidosis and senile plaques can be found in both disease. Both disease also share severe acetylcholine depletion. We evaluated the differences of brain perfusion between DLB and AD using statistical parametric mapping analysis. Twelve DLB (mean age ; 68.8±8.3 years, K-MMSE ; 17.3±6.1) and 51 AD patients (mean age ; 71.4±7.2 years, K-MMSE ; 16.7±4.5), which were matched for age and severity of dementia, participated in this study. Tc-99m HMPAO SPECT was performed for measuring regional cerebral blood flow. Statistical parametric mapping (SPM99) software was used for automatic and objective approach to analyze SPECT image data. The SPECT data of the patients with DLB were compared to patients with AD. Comparison of the two dementia groups (uncorrected p<0.01) revealed significant hypoperfusion in both occipital (both middle occipital gyrus, Rt B no. 18 and Lt cuneus), both parietal (Lt parietal precuneus, Lt B no. 39, Lt inferior parietal lobule and Rt supramarginal gyrus) lobes in DLB compared with AD. Significant hyperperfusion was noted in Rt frontal (sup. frontal gyrus, B no.10, middle frontal gyrus, B no. 9, B no. 11, inf. frontal gyrus), Rt putamen, Lt ant. cingulate gyrus (B no. 24), both cerebellar post. lobe (Lt tuber, Lt declive, Lt tonsil, Rt declive) in DLB compared with AD. We found a significant differences in the cerebral perfusion pattern between DLB and AD. Differential feature of cerebral perfusion in DLB was both occipital hypoperfusion and preserved Rt frontal perfusion compared to AD. Therefore in difficult case of clinical an neuro pathologic diagnosis, brain perfusion SPECT with SPM analysis may be helpful to differentiate DLB from AD

  12. Production of Fumonisin B-2 and B-4 by Aspergillus niger on Grapes and Raisins

    DEFF Research Database (Denmark)

    Mogensen, Jesper Mølgaard; Frisvad, Jens Christian; Thrane, Ulf

    2010-01-01

    The recent discovery of fumonisin production in Aspergillus niger, raises concerns about the presence of these mycotoxins in grapes and raisins as well as other commodities where A. niger is a frequent contaminant. Here we investigate the potential production of fumonisins in A. niger cultured...... on grapes and raisins. Sixty-six A. niger, 4 A. tubingensis, and 16 A. acidus strains isolated from raisins were tested for fumonisin production on laboratory media. Neither A. tubingensis nor A. acidus strains produced fumonisins, but 77% of A. niger strains did. None of the strains produced ochratoxin A....... Ten selected fumonisin producing A. niger strains were further able to produce fumonisin B2 and fumonisin B4 on grapes in the range 171−7841 μg fumonisin B2/kg and 14−1157 μg fumonisin B4/kg. Four selected strains were able to produce fumonisin B2 (5−6476 μg/kg) and fumonisin B4 (12−672 μg...

  13. Regulation of the cellular content of the organic osmolyte taurine in mammalian cells

    DEFF Research Database (Denmark)

    Lambert, Ian H.

    2004-01-01

    regulatory volume decrease, iPLA2, cPLA2, leukotriene D4, reactive oxygen species, NADPH oxidase, protein tyrosine phosphatase, lysophosphatidyl choline......regulatory volume decrease, iPLA2, cPLA2, leukotriene D4, reactive oxygen species, NADPH oxidase, protein tyrosine phosphatase, lysophosphatidyl choline...

  14. Li2Sr4B12O23: A new alkali and alkaline-earth metal mixed borate with [B10O18]6− network and isolated [B2O5]4− unit

    International Nuclear Information System (INIS)

    Zhang Min; Pan Shilie; Han Jian; Yang Zhihua; Su Xin; Zhao Wenwu

    2012-01-01

    A novel ternary lithium strontium borate Li 2 Sr 4 B 12 O 23 crystal with size up to 20 mm×10 mm×4 mm has been grown via the top-seeded solution growth method below 730 °C. Single-crystal XRD analyses showed that Li 2 Sr 4 B 12 O 23 crystallizes in the monoclinic space group P2 1 /c with a=6.4664(4) Å, b=8.4878(4) Å, c=15.3337(8) Å, β=102.02(3)°, Z=2. The crystal structure is composed of [B 10 O 18 ] 6− network and isolated [B 2 O 5 ] 4− unit. The IR spectrum further confirmed the presence of both BO 3 and BO 4 groups. TG-DSC and Transmission spectrum were reported. Band structures and density of states were calculated. - Graphical abstract: A new phase, Li 2 Sr 4 B 12 O 23 , has been discovered in the ternary M 2 O–M′O–B 2 O 3 (M=alkali-metal, M′=alkalineearth metal) system. The crystal structure consists of [B 10 O 18 ] 6− network and isolated [B 2 O 5 ] 4− unit. Highlights: ► Li 2 Sr 4 B 12 O 23 is a a novel borate discovered in the M 2 O–M′O–B 2 O 3 (M=alkali-metal, M′=alkaline-earth metal) system. ► Li 2 Sr 4 B 12 O 23 crystal structure has a three-dimensional crystal structure with [B 10 O 18 ] 6− network and isolated [B 2 O 5 ] 4− unit. ► Sr 1 and Sr 2 are located in two different channels constructed by 3 ∞ [B 10 O 18 ] network.

  15. EphB4 localises to the nucleus of prostate cancer cells

    International Nuclear Information System (INIS)

    Mertens-Walker, Inga; Lisle, Jessica E.; Nyberg, William A.; Stephens, Carson R.; Burke, Leslie; Rutkowski, Raphael; Herington, Adrian C.; Stephenson, Sally-Anne

    2015-01-01

    The EphB4 receptor tyrosine kinase is over-expressed in a variety of different epithelial cancers including prostate where it has been shown to be involved in survival, migration and angiogenesis. We report here that EphB4 also resides in the nucleus of prostate cancer cell lines. We used in silico methods to identify a bipartite nuclear localisation signal (NLS) in the extracellular domain and a monopartite NLS sequence in the intracellular kinase domain of EphB4. To determine whether both putative NLS sequences were functional, fragments of the EphB4 sequence containing each NLS were cloned to create EphB4NLS-GFP fusion proteins. Localisation of both NLS-GFP proteins to the nuclei of transfected cells was observed, demonstrating that EphB4 contains two functional NLS sequences. Mutation of the key amino residues in both NLS sequences resulted in diminished nuclear accumulation. As nuclear translocation is often dependent on importins we confirmed that EphB4 and importin-α can interact. To assess if nuclear EphB4 could be implicated in gene regulatory functions potential EphB4-binding genomic loci were identified using chromatin immunoprecipitation and Lef1 was confirmed as a potential target of EphB4-mediated gene regulation. These novel findings add further complexity to the biology of this important cancer-associated receptor. - Highlights: • The EphB4 protein can be found in the nucleus of prostate cancer cell lines. • EphB4 contains two functional nuclear localisation signals. • Chromatin immunoprecipitation has identified potential genome sequences to which EphB4 binds. • Lef1 is a confirmed target for EphB4-mediated gene regulation

  16. EphB4 localises to the nucleus of prostate cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Mertens-Walker, Inga, E-mail: inga.mertenswalker@qut.edu.au [Institute of Health and Biomedical Innovation, Queensland University of Technology, Woolloongabba, QLD (Australia); Australian Prostate Cancer Research Centre—Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba 4102, QLD (Australia); Lisle, Jessica E. [Institute of Health and Biomedical Innovation, Queensland University of Technology, Woolloongabba, QLD (Australia); Australian Prostate Cancer Research Centre—Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba 4102, QLD (Australia); Nyberg, William A. [Institute of Health and Biomedical Innovation, Queensland University of Technology, Woolloongabba, QLD (Australia); Stephens, Carson R. [Institute of Health and Biomedical Innovation, Queensland University of Technology, Woolloongabba, QLD (Australia); Australian Prostate Cancer Research Centre—Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba 4102, QLD (Australia); Burke, Leslie [Institute of Health and Biomedical Innovation, Queensland University of Technology, Woolloongabba, QLD (Australia); Rutkowski, Raphael; Herington, Adrian C.; Stephenson, Sally-Anne [Institute of Health and Biomedical Innovation, Queensland University of Technology, Woolloongabba, QLD (Australia); Australian Prostate Cancer Research Centre—Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba 4102, QLD (Australia)

    2015-04-10

    The EphB4 receptor tyrosine kinase is over-expressed in a variety of different epithelial cancers including prostate where it has been shown to be involved in survival, migration and angiogenesis. We report here that EphB4 also resides in the nucleus of prostate cancer cell lines. We used in silico methods to identify a bipartite nuclear localisation signal (NLS) in the extracellular domain and a monopartite NLS sequence in the intracellular kinase domain of EphB4. To determine whether both putative NLS sequences were functional, fragments of the EphB4 sequence containing each NLS were cloned to create EphB4NLS-GFP fusion proteins. Localisation of both NLS-GFP proteins to the nuclei of transfected cells was observed, demonstrating that EphB4 contains two functional NLS sequences. Mutation of the key amino residues in both NLS sequences resulted in diminished nuclear accumulation. As nuclear translocation is often dependent on importins we confirmed that EphB4 and importin-α can interact. To assess if nuclear EphB4 could be implicated in gene regulatory functions potential EphB4-binding genomic loci were identified using chromatin immunoprecipitation and Lef1 was confirmed as a potential target of EphB4-mediated gene regulation. These novel findings add further complexity to the biology of this important cancer-associated receptor. - Highlights: • The EphB4 protein can be found in the nucleus of prostate cancer cell lines. • EphB4 contains two functional nuclear localisation signals. • Chromatin immunoprecipitation has identified potential genome sequences to which EphB4 binds. • Lef1 is a confirmed target for EphB4-mediated gene regulation.

  17. Mast cells in citric acid-induced cough of guinea pigs

    International Nuclear Information System (INIS)

    Lai, Y.-L.; Lin, T.-Y.

    2005-01-01

    It was demonstrated previously that mast cells play an important role in citric acid (CA)-induced airway constriction. To investigate the role of mast cells in CA-induced cough, three experiments were carried out in this study. In the first experiment, 59 guinea pigs were employed and we used compound 48/80 to deplete mast cells, cromolyn sodium to stabilize mast cells, MK-886 to inhibit leukotriene synthesis, pyrilamine to antagonize histamine H 1 receptor, methysergide to antagonize serotonin receptor, and indomethacin to inhibit cyclooxygenase. In the second experiment, 56 compound 48/80-pretreated animals were divided into two parts; the first one was used to test the role of exogenous leukotriene (LT) C 4 , while the second one to test the role of exogenous histamine in CA-induced cough. Each animal with one of the above pretreatments was exposed sequentially to saline (baseline) and CA (0.6 M) aerosol, each for 3 min. Then, cough was recorded for 12 min using a barometric body plethysmograph. In the third experiment, the activation of mast cells upon CA inhalation was investigated by determining arterial plasma histamine concentration in 17 animals. Exposure to CA induced a marked increase in cough number. Compound 48/80, cromolyn sodium, MK-886 and pyrilamine, but not indomethacin or methysergide, significantly attenuated CA-induced cough. Injection of LTC 4 or histamine caused a significant increase in CA-induced cough in compound 48/80-pretreated animals. In addition, CA inhalation caused significant increase in plasma histamine concentration, which was blocked by compound 48/80 pretreatment. These results suggest that mast cells play an important role in CA aerosol inhalation-induced cough via perhaps mediators LTs and histamine

  18. Attenuated Escherichia coli strains expressing the colonization factor antigen I (CFA/I) and a detoxified heat-labile enterotoxin (LThK63) enhance clearance of ETEC from the lungs of mice and protect mice from intestinal ETEC colonization and LT-induced fluid accumulation.

    Science.gov (United States)

    Byrd, Wyatt; Boedeker, Edgar C

    2013-03-15

    mice as the immunized mice induced insufficient intestinal anti-LT antibody to neutralize the activity of the enterotoxin. These results show that our ETEC vaccine induced serum and mucosal antibody responses to CFA/I and LT after mucosal administration which then acted to protect the immunized mice against lung and intestinal colonization, as well as, intestinal fluid accumulation. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. 32 CFR 806b.4 - Privacy Act complaints.

    Science.gov (United States)

    2010-07-01

    ... be identified, the local Privacy Act officer will assume these duties. Issues that cannot be resolved... 32 National Defense 6 2010-07-01 2010-07-01 false Privacy Act complaints. 806b.4 Section 806b.4 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE ADMINISTRATION PRIVACY ACT...

  20. 11B-NMR study of low-temperature phase transition in CuB2O4

    International Nuclear Information System (INIS)

    Yasuda, Y; Nakamura, H; Fujii, Y; Kikuchi, H; Chiba, M; Yamamoto, Y; Hori, H; Petrakovskii, G; Popov, M; Bezmaternikh, L

    2007-01-01

    The material CuB 2 O 4 presents a variety of phases in the B-T phase diagram, caused by the frustration and the Dzialoshinskii-Moriya interaction. In order to investigate the nature of the phase transitions, a 11 B-NMR experiment on CuB 2 O 4 has been performed under an applied magnetic field along the a-axis down to 0.4 K. A new incommensurate-incommensurate phase transition has been found at 0.8 K under a field of 0.5 T. Further, another phase transition has been observed at 4.7 K under a field of about 2 T, which is consistent with the transition reported by the neutron diffraction experiment

  1. Vital role for cyclophilin B (CypB) in asexual development, dimorphic transition and virulence of Beauveria bassiana.

    Science.gov (United States)

    Chu, Zhen-Jian; Sun, Huan-Huan; Ying, Sheng-Hua; Feng, Ming-Guang

    2017-08-01

    Cyclophilin B (CypB) was previously revealed as one of many putative secretory proteins in the transcriptome of Beauveria bassiana infection to a lepidopteran pest. Here we show a main localization of CypB in hyphal cell walls and septa and its essential role in the in vitro and in vivo asexual cycles of the fungal insect pathogen. Deletion of cypB reduced colony growth by 16-42% on two rich media and 30 scant media with different carbon or nitrogen sources. The deletion mutant suffered a delayed conidiation on a standard medium and a final 47% reduction in conidial yield, accompanied with drastic transcript depression of several key genes required for conidiation and conidial maturation. The mutant conidia required 10h longer to germinate 50% at optimal 25°C than wild-type conidia. Intriguingly, cultivation of the mutant conidia in a trehalose-peptone broth mimic to insect hemolymph resulted in 83% reduction in blastospore yield but only slight decrease in biomass level, indicating severe defects in transition of hyphae to blastospores. LT 50 for the deletion mutant against Galleria mellonella larvae through normal cuticle infection was prolonged to 7.4d from a wild-type estimate of 4.7d. During colony growth, additionally, the deletion mutant displayed hypersensitivity to Congo red, menadione, H 2 O 2 and heat shock but increased tolerance to cyclosporine A and rapamycin. All of changes were restored by targeted gene complementation. Altogether, CypB takes part in sustaining normal growth, aerial conidiation, conidial germination, dimorphic transition, stress tolerance and pathogenicity in B. bassiana. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Spin dynamics of superfluid 3He-B in a slab geometry

    International Nuclear Information System (INIS)

    Ishikawa, O.; Sasaki, Y.; Mizusaki, T.; Hirai, A.; Tsubota, M.

    1989-01-01

    The spin dynamics and the spin relaxation mechanisms of the superfluid 3 He-B were studied by using the NMR method in a slab geometry, where the superfluid 3 He-B was confined between narrow parallel plates with a gap smaller than the healing length of the n-texture and the magnetic field was applied and to the plates. The relaxation parameter in the Leggett-Takagi (LT) equations was determined from a line width measurement of the transverse CW NMR. By using the pulsed NMR method, spin dynamics were studied in the nonlinear region. The observed spin dynamics were in good agreement with a numerical calculation of the LT equations together with the relaxation parameter determined by the CW NMR. When the tipping angle became larger than a certain critical value, the superfluid 3 He-B entered the Brinkman-Smith (BS) state. In this case, they observed the slow relaxation process in the BS state and then the rapid recovery process from the BS state to the initial non-Leggett configuration. The slow process in the BS state was attributed to the surface relaxation mechanism due to the torque from the surface-field energy

  3. Meningococcal B Vaccination (4CMenB in Infants and Toddlers

    Directory of Open Access Journals (Sweden)

    Susanna Esposito

    2015-01-01

    Full Text Available Neisseria meningitidis is a Gram-negative pathogen that actively invades its human host and leads to the development of life-threatening pathologies. One of the leading causes of death in the world, N. meningitidis can be responsible for nearly 1,000 new infections per 100,000 subjects during an epidemic period. The bacterial species are classified into 12 serogroups, five of which (A, B, C, W, and Y cause the majority of meningitides. The three purified protein conjugate vaccines currently available target serogroups A, C, W, and Y. Serogroup B has long been a challenge but the discovery of the complete genome sequence of an MenB strain has allowed the development of a specific four-component vaccine (4CMenB. This review describes the pathogenetic role of N. meningitidis and the recent literature concerning the new meningococcal vaccine.

  4. FIRST 5-DAYS FOLLOW-UP AND CORRELATION STUDY BETWEEN URINARY CYSTEINYL LEUKO TRIENES AND EDEMA VALUES IN PRIMARY SPONTANEOUS SUPRATENTORIAL INTRACEREBRAL HEMO RRHAGE

    Directory of Open Access Journals (Sweden)

    Dolnenec-Baneva Natalia

    2014-07-01

    Full Text Available Background: After intracerebral hemorrhage cysteinyl leukotrienes (C4, D4, E4 are synthetisized in the contact brain parenchyma-extravasated blood and participate in producing of edema formation. The study aim is a 5-days follow up (admittance/3thday/5thday of urinary cysteinyl leukotrienes, hematoma and edema volume in patients with primary spontaneous supratentorial intracerebral hemorrhage and to determine the relationship: edema/haematoma and edema/leuko trienes. Methods: An enzyme immunoassay for leukotrienes measuring in the urine samples from 62 patients with hemorrhage during the first 5 days ( admittance/3thday/5thday and 80 health controls is used. Hematoma and edema volume is visualised and measured by computed-tomography. Results: Admission values of leukotrienes were significantly higher in the hemorrhagic patients (min =268.61; max = 5787.36; mean = 1842.20 ± 1413.19 pg/ml/mg creatinine versus control subjects (min =297.8; max = 1684.2; mean = 918.6 ± 332 (p 0.05. The edema (mean: 12.86 ±13.52; 22.38 ± 21.10; 28.45 ± 29.41 cm3 showed very high significance (p 0.05 of moderate strength is found between edema and hematoma; and significant positive correlation (r = 0.6; p 0.05 at admittance, r = – 0.05 (p >0.05 on the 3th day (nonexistence of linear correlation, the sign minus presents their tendency for the opposite movement in their values and r = 0.2 (p > 0.05 on the 5thday are found (positive linear nonsignificant correlation of slight strength. Conclusion: Significant urinary leukotrienes excretion (a brain capacity for significant leukotrienes synthesis and significant edema progression versus constant haematoma are found. The edema size followed the hematoma size of moderate extent. The edema showed an inverse dependence of the leukotrienes (atendency for opposite movement of their values, the high leukotrienes values at admittance bring to greater edema volume on the third/the fifth day, respectively. Elevated cysteinyl

  5. Cellular uptake of exogenous calcineurin B is dependent on TLR4/MD2/CD14 complexes, and CnB is an endogenous ligand of TLR4.

    Science.gov (United States)

    Yang, Jinju; Qin, Nannan; Zhang, Hongwei; Yang, Rui; Xiang, Benqiong; Wei, Qun

    2016-04-19

    Our previous research showed that recombinant calcineurin B (rhCnB) stimulates cytokine secretion by immune cells, probably through TLR4. Exogenous CnB can be incorporated into many different tumour cells in vitro, but the mode of uptake and receptors required remain unknown. Here, we report that exogenous CnB is taken up by cells in a time- and concentration-dependent manner via clathrin-dependent receptor-mediated internalization. Our findings further confirm that uptake is mediated by the TLR4/MD2 complex together with the co-receptor CD14. The MST results revealed a high affinity between CnB and the TLR4 receptor complex. No binding was detected between CnB and LPS. CnB inhibited the uptake of LPS, and LPS also inhibited the uptake of CnB. These results indicate that the uptake of exogenous CnB did not occur through LPS and that CnB was not a chaperone of LPS. Thus, we conclude that TLR4 receptor complexes were required for the recognition and internalization of exogenous CnB. CnB could be a potential endogenous ligand of TLR4 and function as an agonist of TLR4. These properties of CnB support its potential for development as an anti-cancer drug.

  6. A SEARCH FOR L/T TRANSITION DWARFS WITH Pan-STARRS1 AND WISE: DISCOVERY OF SEVEN NEARBY OBJECTS INCLUDING TWO CANDIDATE SPECTROSCOPIC VARIABLES

    Energy Technology Data Exchange (ETDEWEB)

    Best, William M. J.; Liu, Michael C.; Magnier, Eugene A.; Aller, Kimberly M.; Burgett, W. S.; Chambers, K. C.; Hodapp, K. W.; Kaiser, N.; Kudritzki, R.-P.; Morgan, J. S.; Tonry, J. L.; Wainscoat, R. J. [Institute for Astronomy, University of Hawaii at Manoa, Honolulu, HI 96822 (United States); Deacon, Niall R. [Max Planck Institute for Astronomy, Koenigstuhl 17, D-69117 Heidelberg (Germany); Dupuy, Trent J. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Redstone, Joshua [Facebook, 335 Madison Ave, New York, NY 10017-4677 (United States); Price, P. A., E-mail: wbest@ifa.hawaii.edu [Department of Astrophysical Sciences, Princeton University, Princeton, NJ 08544 (United States)

    2013-11-10

    We present initial results from a wide-field (30,000 deg{sup 2}) search for L/T transition brown dwarfs within 25 pc using the Pan-STARRS1 and Wide-field Infrared Survey Explorer (WISE) surveys. Previous large-area searches have been incomplete for L/T transition dwarfs, because these objects are faint in optical bands and have near-infrared (near-IR) colors that are difficult to distinguish from background stars. To overcome these obstacles, we have cross-matched the Pan-STARRS1 (optical) and WISE (mid-IR) catalogs to produce a unique multi-wavelength database for finding ultracool dwarfs. As part of our initial discoveries, we have identified seven brown dwarfs in the L/T transition within 9-15 pc of the Sun. The L9.5 dwarf PSO J140.2308+45.6487 and the T1.5 dwarf PSO J307.6784+07.8263 (both independently discovered by Mace et al.) show possible spectroscopic variability at the Y and J bands. Two more objects in our sample show evidence of photometric J-band variability, and two others are candidate unresolved binaries based on their spectra. We expect our full search to yield a well-defined, volume-limited sample of L/T transition dwarfs that will include many new targets for study of this complex regime. PSO J307.6784+07.8263 in particular may be an excellent candidate for in-depth study of variability, given its brightness (J = 14.2 mag) and proximity (11 pc)

  7. Toxicity and immunogenicity of Enterotoxigenic Escherichia coli heat-labile and heat-stable toxoid fusion 3xSTa(A14Q-LT(S63K/R192G/L211A in a murine model.

    Directory of Open Access Journals (Sweden)

    Chengxian Zhang

    Full Text Available Diarrhea is the second leading cause of death to young children. Enterotoxigenic Escherichia coli (ETEC are the most common bacteria causing diarrhea. Adhesins and enterotoxins are the virulence determinants in ETEC diarrhea. Adhesins mediate bacterial attachment and colonization, and enterotoxins including heat-labile (LT and heat-stable type Ib toxin (STa disrupt fluid homeostasis in host cells that leads to fluid hyper-secretion and diarrhea. Thus, adhesins and enterotoxins have been primarily targeted in ETEC vaccine development. A recent study reported toxoid fusions with STa toxoid (STa(P13F fused at the N- or C-terminus, or inside the A subunit of LT(R192G elicited neutralizing antitoxin antibodies, and suggested application of toxoid fusions in ETEC vaccine development (Liu et al., Infect. Immun. 79:4002-4009, 2011. In this study, we generated a different STa toxoid (STa(A14Q and a triple-mutant LT toxoid (LT(S63K/R192G/L211A, tmLT, constructed a toxoid fusion (3xSTa(A14Q-tmLT that carried 3 copies of STa(A14Q for further facilitation of anti-STa immunogenicity, and assessed antigen safety and immunogenicity in a murine model to explore its potential for ETEC vaccine development. Mice immunized with this fusion antigen showed no adverse effects, and developed antitoxin antibodies particularly through the IP route. Anti-LT antibodies were detected and were shown neutralizing against CT in vitro. Anti-STa antibodies were also detected in the immunized mice, and serum from the IP immunized mice neutralized STa toxin in vitro. Data from this study indicated that toxoid fusion 3xSTa(A14Q-tmLT is safe and can induce neutralizing antitoxin antibodies, and provided helpful information for vaccine development against ETEC diarrhea.

  8. Lumbar lordosis restoration following single-level instrumented fusion comparing 4 commonly used techniques.

    Science.gov (United States)

    Dimar, John R; Glassman, Steven D; Vemuri, Venu M; Esterberg, Justin L; Howard, Jennifer M; Carreon, Leah Y

    2011-11-09

    A major sequelae of lumbar fusion is acceleration of adjacent-level degeneration due to decreased lumbar lordosis. We evaluated the effectiveness of 4 common fusion techniques in restoring lordosis: instrumented posterolateral fusion, translumbar interbody fusion, anteroposterior fusion with posterior instrumentation, and anterior interbody fusion with lordotic threaded (LT) cages (Medtronic Sofamor Danek, Memphis, Tennessee). Radiographs were measured preoperatively, immediately postoperatively, and a minimum of 6 months postoperatively. Parameters measured included anterior and posterior disk space height, lumbar lordosis from L3 to S1, and surgical level lordosis.No significant difference in demographics existed among the 4 groups. All preoperative parameters were similar among the 4 groups. Lumbar lordosis at final follow-up showed no difference between the anteroposterior fusion with posterior instrumentation, translumbar interbody fusion, and LT cage groups, although the posterolateral fusion group showed a significant loss of lordosis (-10°) (Plordosis and showed maintenance of anterior and posterior disk space height postoperatively compared with the other groups. Instrumented posterolateral fusion produces a greater loss of lordosis compared with anteroposterior fusion with posterior instrumentation, translumbar interbody fusion, and LT cages. Maintenance of lordosis and anterior and posterior disk space height is significantly better with anterior interbody fusion with LT cages. Copyright 2011, SLACK Incorporated.

  9. Levothyroxine liquid solution versus tablet form for replacement treatment in pregnant women.

    Science.gov (United States)

    Cappelli, Carlo; Negro, Roberto; Pirola, Ilenia; Gandossi, Elena; Agosti, Barbara; Castellano, Maurizio

    2016-01-01

    To evaluate the need and the magnitude of levothyroxine (LT4) increase in hypothyroid pregnant women on liquid compared to tablet formulations. Patients were recruited by searching our "thyroid patients" database. The selection criteria were as follows: a) pregnant women on treatment for hypothyroidism (both liquid and tablet LT4) who gave birth at our hospital between February 2012 and January 2014; b) thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels obtained at least 3 months before missed menstrual cycle, with a TSH value less than 2.5 mIU/L and c) TSH and FT4 obtained within 12 weeks of pregnancy, and each month subsequently. During pregnancy, 8/31 (25.5%) of the women had to increase the dosage of LT4. Of these, 7/17 (41.2%) were on LT4 replacement therapy with tablets, and 1/14 (7.1%) with liquid formulation (p = 0.038). Daily LT4 was significantly increased in the liquid group only (52.9 ± 19.5 versus 67.5 ± 19.2 mcg/day (p = 0.013). A logistic regression analysis showed that the treatment with LT4 tablets was the only predictor of LT4 increase (OR: 0.44; 95% CI: 0.04-0.83; p = 0.031). Pregnant women on optimal replacement therapy before pregnancy require an increase of LT4 dosage more often when on a tablet than liquid formulation.

  10. Ordering effects in benzo[1,2-b:4,5-b']difuran-thieno[3,4-c]pyrrole-4,6- dione polymers with >7% solar cell efficiency

    KAUST Repository

    Warnan, Julien

    2014-05-15

    Benzo[1,2-b:4,5-b\\']difuran-thieno[3,4-c]pyrrole-4,6-dione (PBDFTPD) polymers prepared by microwave-assisted synthesis can achieve power conversion efficiencies (PCEs) >7% in bulk-heterojunction solar cells with phenyl-C61/71-butyric acid methyl ester (PCBM). In "as-cast" PBDFTPD-based devices solution-processed without a small-molecule additive, high PCEs can be obtained in spite of the weak propensity of the polymers to self-assemble and form π-aggregates in thin films. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. CONTEMPT-LT/028: a computer program for predicting containment pressure-temperature response to a loss-of-coolant accident

    International Nuclear Information System (INIS)

    Hargroves, D.W.; Metcalfe, L.J.; Wheat, L.L.; Niederauer, G.F.; Obenchain, C.F.

    1979-03-01

    CONTEMPT-LT is a digital computer program, written in FORTRAN IV, developed to describe the long-term behavior of water-cooled nuclear reactor containment systems subjected to postulated loss-of-coolant accident (LOCA) conditions. The program calculates the time variation of compartment pressures, temperatures, mass and energy inventories, heat structure temperature distributions, and energy exchange with adjacent compartments. The program is capable of describing the effects of leakage on containment response. Models are provided to describe fan cooler and cooling spray engineered safety systems. An annular fan model is also provided to model pressure control in the annular region of dual containment systems. Up to four compartments can be modeled with CONTEMPT-LT, and any compartment except the reactor system may have both a liquid pool region and an air--vapor atmosphere region above the pool. Each region is assumed to have a uniform temperature, but the temperatures of the two regions may be different

  12. Magnetic anomaly in superconducting TmRh4B4

    International Nuclear Information System (INIS)

    Smith, J.L.; Huang, C.Y.; Tsou, J.J.; Ho, J.C.

    1978-01-01

    The magnetic and superconducting properties of TmRh 4 B 4 (which becomes superconducting at 9.6 K) by means of ac and dc magnetic susceptibility and specific heat measurements are investigated. At 10.7 K, an ac susceptibility peak similar to those found in spin glasses has been observed. In addition, a pronounced specific heat peak has been observed at 11.4 K. The susceptibility peak is essentially unaffected by substitution of 1% Lu or Er for the Tm, but it diminishes when much larger amounts of Er are substituted. The physical origin of this anomalous peak will be discussed

  13. 40 CFR 721.9662 - Thieno[3,4-b]-1,4-dioxin, 2,3-dihydro- (9CI).

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Thieno[3,4-b]-1,4-dioxin, 2,3-dihydro... Specific Chemical Substances § 721.9662 Thieno[3,4-b]-1,4-dioxin, 2,3-dihydro- (9CI). (a) Chemical...-b]-1,4-dioxin, 2,3-dihydro- (9CI) (PMN P-95-1825; CAS No. 126213-50-1) is subject to reporting under...

  14. Serum levels of interleukin-6 and interleukin-8 as diagnostic markers of acute pyelonephritis in children

    Directory of Open Access Journals (Sweden)

    Abolfazl Mahyar

    2013-05-01

    Full Text Available &lt;b&gt;Purpose:&lt;/b&gt; Early diagnosis and treatment of acute pyelonephritis in children is of special importance in order to prevent serious complications. This study was conducted to determine the diagnostic value of serum interleukin (IL-6 and IL-8 in children with acute pyelonephritis. &lt;b&gt;Methods:&lt;/b&gt; Eighty seven patients between 1 month to 12 years old with urinary tract infection (UTI were divided into 2 groups based on the result of 99m-technetium dimercapto-succinic acid (DMSA renal scan: acute pyelonephritis (n=37 and lower UTI (n=50 groups. White blood cell (WBC count, neutrophil (Neutl count, erythrocyte sedimentation rate (ESR, C-reactive protein (CRP concentration, platelet count, and serum IL-6 and IL-8 concentrations of both groups were measured and compared . &lt;b&gt;Results:&lt;/b&gt; There was a significant difference between two groups regarding WBC count, Neutl count, ESR, and CRP concentration (P&lt;0.05. In addition, the difference between the two groups regarding serum IL-6 and IL-8 concentrations was not significant (IL-6, 60 and 35.4 pg/mL and IL-8, 404 and 617 pg/mL, respectively. The sensitivity and specificity of serum IL-6 and IL-8 for diagnosis of acute pyelonephritis were 73%, 42% and 78%, 32%, respectively. Sensitivity, specificity, negative and positive predictive values of serum IL-6 and IL-8 were less than those of acute phase serum reactants such as CRP. &lt;b&gt;Conclusion:&lt;/b&gt; This study showed that there was no significant difference between acute pyelonephritis and lower UTI groups regarding serum IL-6 and IL-8 levels. Therefore, despite confirming results of previous studies, it seems that IL-6 and IL-8 are not suitable markers for differentiating between acute pyelonephritis and lower UTI.

  15. Value of impulse oscillometry in evaluating the illness in children with asthma and analysis of its correlation with serum indicators

    Directory of Open Access Journals (Sweden)

    Cui-Fen Bai

    2016-05-01

    Full Text Available Objective: To Value of impulse oscillometry in evaluating the illness in children with asthma and its correlation with serum indicators. Methods: Children with asthma attack, children with asthma remission and healthy children were selected for study, impulse oscillometry was conducted to obtain related parameters, and serum and peripheral blood were collected to detect related indicators. Results: Zrs, R5, R20, R5-R20, absolute value of X5 and Fres of asthma attack group and asthma remission group were higher than those of control group, eosinophil, YKL-40, Hes-1, Cyr61, Eotaxin, IgE, IgG4, LT-B4, LT-C4, LT-D4 and Cys-LT contents in peripheral blood were higher than those of control group, positive proportion of Th2, Th17, cTfh and Th19 in peripheral blood were higher than those of control group, and positive proportion of Th1 and Treg in peripheral blood were lower than those of control group; the changes of above indicators of asthma attack group were more significant than those of asthma remission group; Zrs, R5, R20, R5-R20, absolute value of X5 and Fres were positively correlated with eosinophil, YKL-40, Hes-1, Cyr61, Eotaxin, IgE, IgG4, LT-B4, LT-C4, LTD4 and Cys-LT contents in peripheral blood as well as positive proportion of Th2, Th17, cTfh and Th19 in peripheral blood, and negatively correlated with positive proportion of Th1 and Treg in peripheral blood. Conclusion: Impulse oscillometry detection can provide evidence for diagnosis of bronchial asthma and judgment of its illness, and IOS-related parameters can judge the abnormal degree of inflammatory response and immune response.

  16. 17 CFR 260.11b-4 - Definition of “cash transaction” in section 311(b)(4).

    Science.gov (United States)

    2010-04-01

    ... transaction”, as used in section 311(b)(4), means any transaction in which full payment for goods or securities sold is made within 7 days after delivery of the goods or securities in currency or in checks or...

  17. Effect of the Ti/B{sub 4}C mole ratio on the reaction products and reaction mechanism in an Al–Ti–B{sub 4}C powder mixture

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jingjing [Key Laboratory of Liquid Structure and Heredity of Materials, Ministry of Education, Shandong University, Jinan 250100 (China); Light Metal Division, Korea Institute of Materials Science, Changwon 642-831 (Korea, Republic of); Lee, Jung-Moo, E-mail: jmoolee@kims.re.kr [Light Metal Division, Korea Institute of Materials Science, Changwon 642-831 (Korea, Republic of); Cho, Young-Hee; Kim, Su-Hyeon [Light Metal Division, Korea Institute of Materials Science, Changwon 642-831 (Korea, Republic of); Yu, Huashun [Key Laboratory of Liquid Structure and Heredity of Materials, Ministry of Education, Shandong University, Jinan 250100 (China)

    2014-10-15

    The effect of the Ti/B{sub 4}C mole ratio on the fabrication behavior of Al composites is investigated using Al–Ti–B{sub 4}C powder mixtures as reactants. The quick spontaneous infiltration (QSI) process combined with the combustion reaction and DTA analysis were used. According to the thermodynamic predictions, which are verified in the experimental results, TiB{sub 2} is formed in all the samples whereas TiC is only formed in reactants with a Ti/B{sub 4}C mole ratio of more than two. The C atoms from the reacted B{sub 4}C do not move into TiC but instead they move into Al{sub 3}BC or Al{sub 4}C{sub 3} when the Ti/B{sub 4}C mole ratio is less than two. In addition, the reaction mechanism with a Ti/B{sub 4}C mole ratio of 0.75 is investigated extensively. - Highlights: • The critical role of the Ti/B{sub 4}C mole ratio on the reaction products of Al–Ti–B{sub 4}C was studied using experiments. • The experimental results are also supported by thermodynamic calculations presented in this paper. • The reaction mechanism with a Ti/B{sub 4}C mole ratio of 0.75 is investigated extensively.

  18. Complete genomic sequences for hepatitis C virus subtypes 4b, 4c, 4d, 4g, 4k, 4l, 4m, 4n, 4o, 4p, 4q, 4r and 4t.

    Science.gov (United States)

    Li, Chunhua; Lu, Ling; Wu, Xianghong; Wang, Chuanxi; Bennett, Phil; Lu, Teng; Murphy, Donald

    2009-08-01

    In this study, we characterized the full-length genomic sequences of 13 distinct hepatitis C virus (HCV) genotype 4 isolates/subtypes: QC264/4b, QC381/4c, QC382/4d, QC193/4g, QC383/4k, QC274/4l, QC249/4m, QC97/4n, QC93/4o, QC139/4p, QC262/4q, QC384/4r and QC155/4t. These were amplified, using RT-PCR, from the sera of patients now residing in Canada, 11 of which were African immigrants. The resulting genomes varied between 9421 and 9475 nt in length and each contains a single ORF of 9018-9069 nt. The sequences showed nucleotide similarities of 77.3-84.3 % in comparison with subtypes 4a (GenBank accession no. Y11604) and 4f (EF589160) and 70.6-72.8 % in comparison with genotype 1 (M62321/1a, M58335/1b, D14853/1c, and 1?/AJ851228) reference sequences. These similarities were often higher than those currently defined by HCV classification criteria for subtype (75.0-80.0 %) and genotype (67.0-70.0 %) division, respectively. Further analyses of the complete and partial E1 and partial NS5B sequences confirmed these 13 'provisionally assigned subtypes'.

  19. Production of thermoluminescent dosemeters based on MgB4O7: Dy and MgB4O7: Tm

    International Nuclear Information System (INIS)

    Souza, Luiza Freire de; Souza, Divanizia N.

    2013-01-01

    The thermoluminescent dosimetry (TL) is a well-established technique for the detection of ionizing radiation in hospitals, clinics, and industrial establishments where there is the need to quantify the radiation. For this practice is require the use phosphors which are sensitive to radiation. Some phosphors are already commonly used in this practice, for example, TLD-100 (LiF: Mg, Ti), CaSO 4 :Tm and CaSO 4 :Dy. A compound that was most recently introduced in dosimetry and has many advantageous features to detect neutrons, electrons and gamma is the magnesium tetraborate (MgB 4 O 7 ), but the undoped material is not good for dosimetry, since signal does not show satisfactory thermoluminescence. The present work presents the analysis of the compound MgB 4 O 7 when doped with rare earth elements, thulium (Tm) and dysprosium (Dy). The production of MgB 4 O 7 : Dy and MgB 4 O 7 : Tm occurred under acidic conditions. Following the process of crystal growth, several tests were made on phosphors produced to verify the quality of materials as TL dosimeter. Initially, was made the identification of the crystalline phases found in the material, using the technique of X-ray diffractometry, and then were evaluated and compared the TL emission curves of the crystals with two different types of dopants, to this, the samples were irradiated with different radiation sources: 137 Cs (0,66 MeV), 60 Co (1.25 MeV) and X-rays (0.41 MeV) and based on the results was evaluated the energy dependence of phosphors. Another characteristic analyzed, was the decay of TL signal for the material (fading). The results show that the material can be an excellent TL dosimeter when doped with rare earth elements Dy and Tm. (author)

  20. Ixodes ricinus tick lipocalins: identification, cloning, phylogenetic analysis and biochemical characterization.

    Directory of Open Access Journals (Sweden)

    Jérôme Beaufays

    Full Text Available BACKGROUND: During their blood meal, ticks secrete a wide variety of proteins that interfere with their host's defense mechanisms. Among these proteins, lipocalins play a major role in the modulation of the inflammatory response. METHODOLOGY/PRINCIPAL FINDINGS: Screening a cDNA library in association with RT-PCR and RACE methodologies allowed us to identify 14 new lipocalin genes in the salivary glands of the Ixodes ricinus hard tick. A computational in-depth structural analysis confirmed that LIRs belong to the lipocalin family. These proteins were called LIR for "Lipocalin from I. ricinus" and numbered from 1 to 14 (LIR1 to LIR14. According to their percentage identity/similarity, LIR proteins may be assigned to 6 distinct phylogenetic groups. The mature proteins have calculated pM and pI varying from 21.8 kDa to 37.2 kDa and from 4.45 to 9.57 respectively. In a western blot analysis, all recombinant LIRs appeared as a series of thin bands at 50-70 kDa, suggesting extensive glycosylation, which was experimentally confirmed by treatment with N-glycosidase F. In addition, the in vivo expression analysis of LIRs in I. ricinus, examined by RT-PCR, showed homogeneous expression profiles for certain phylogenetic groups and relatively heterogeneous profiles for other groups. Finally, we demonstrated that LIR6 codes for a protein that specifically binds leukotriene B4. CONCLUSIONS/SIGNIFICANCE: This work confirms that, regarding their biochemical properties, expression profile, and sequence signature, lipocalins in Ixodes hard tick genus, and more specifically in the Ixodes ricinus species, are segregated into distinct phylogenetic groups suggesting potential distinct function. This was particularly demonstrated by the ability of LIR6 to scavenge leukotriene B4. The other LIRs did not bind any of the ligands tested, such as 5-hydroxytryptamine, ADP, norepinephrine, platelet activating factor, prostaglandins D2 and E2, and finally leukotrienes B4 and C

  1. Role of leukotrienes in NSAID induced gastric ulceration and inflammation in wistar rats

    Directory of Open Access Journals (Sweden)

    Maulik N Gandhi

    2012-06-01

    Full Text Available Objective: To evaluate the effects of Montelukast and Curcumin against indomethacin induced gastric damage in rats in order to assess the role of leukotriene (LTs if any, in non steroidal antiinflammatory drug (NSAID induced gastroinflammation. Methods: The effects of Montelukast (10 mg/kg and Curcumin (100 mg/kg were observed on gastric lesion induced by Indomethacin. The blood samples were analyzed for neutrophil adhesion and lipid peroxide levels in gastric tissue measured spectrophotometrically. The skin vascular permeability study was performed by using compound 48/80 induced vascular permeability model. Results: Montelukast and Curcumin significantly reduced Indomethacin induced gastric lesion score. Pretreatment with Montelukast and Curcumin significantly counteracted Indomethacin induced gastropathy by a combination of its effect on inhibition of neutrophil adherence, through decrease in related production of free radicals that disrupts integrity of stomach mucosa and decrease in vascular permeability as compared to Indomethacin group. The results of the present study further indicates the role of 5-LOX metabolites in NSAIDs induced gastro inflammation and suggests that Montelukast and Curcumin counteracted the Indomethacin induced gastropathy by a combination of its effect on inhibition of neutrophil adherence and through decrease in related production of free radicals that disrupts integrity of stomach mucosa. Conclusions: Experimental data clearly demonstrated the role of LTs was indomethacin induced gastric ulcers. However, inhibition of ulcerogenic events by Montelukast and Curcumin is suggestive of an important balance between COX and 5-LOX products.

  2. Sulfite induces release of lipid mediators by alveolar macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Beck-Speier, I.; Dayal, N.; Maier, L. [GSF - National Research Center for Environment and Health, Neuherberg (Germany). Inst. for Inhalation Biology; Denzlinger, C. [Tuebingen Univ. (Germany). Dept. II, Medical Clinic; Haberl, C. [Tuebingen Univ. (Germany). Dept. III, Medical Clinic

    1998-03-01

    Air pollutants are supposed to modulate physiological responses of alveolar macrophages (AM). This study was addressed to the question whether at neutral pH sulfur(IV) species in comparison to sulfur(VI) species cause AM to release proinflammatory mediators and which pathways are involved in their generation. Supernatants obtained from canine AM treated with sulfite (0.1 mM to 2 mM) enhanced the respiratory burst of canine neutrophils, measured by lucigenin-dependent chemiluminescence, whereas supernatants derived from AM treated with sulfate (1 mM) did not. The neutrophil-stimulating activity released by sulfite-treated AM consisted of platelet-activating factor (PAF) and leukotriene B{sub 4} (LTB{sub 4}) as shown by desensitization of the platelet-activating factor (PAF) and leukotriene B{sub 4} (LTB{sub 4}) as shown by desensitization of the corresponding receptors. Inhibitors of phospholipase A{sub 2} substantially suppressed release of neutrophil-stimulating activity by sulfite-treated AM. Inhibition of 5-lipoxygenase in sulfite-treated AM also reduced neutrophil-stimulating activity, while inhibition of cyclooxygenase had no effect. In conclusion, sulfite induces AM to release lipid mediators via phospholipase A{sub 2}- and 5-lipoxygenase-dependent pathways. These mediators activate neutrophils via the receptors for PAF and LTB{sub 4}. (orig.)

  3. Cutting Edge: 2B4-Mediated Coinhibition of CD4+ T Cells Underlies Mortality in Experimental Sepsis.

    Science.gov (United States)

    Chen, Ching-Wen; Mittal, Rohit; Klingensmith, Nathan J; Burd, Eileen M; Terhorst, Cox; Martin, Greg S; Coopersmith, Craig M; Ford, Mandy L

    2017-09-15

    Sepsis is a leading cause of death in the United States, but the mechanisms underlying sepsis-induced immune dysregulation remain poorly understood. 2B4 (CD244, SLAM4) is a cosignaling molecule expressed predominantly on NK cells and memory CD8 + T cells that has been shown to regulate T cell function in models of viral infection and autoimmunity. In this article, we show that 2B4 signaling mediates sepsis lymphocyte dysfunction and mortality. 2B4 expression is increased on CD4 + T cells in septic animals and human patients at early time points. Importantly, genetic loss or pharmacologic inhibition of 2B4 significantly increased survival in a murine cecal ligation and puncture model. Further, CD4-specific conditional knockouts showed that 2B4 functions on CD4 + T cell populations in a cell-intrinsic manner and modulates adaptive and innate immune responses during sepsis. Our results illuminate a novel role for 2B4 coinhibitory signaling on CD4 + T cells in mediating immune dysregulation. Copyright © 2017 by The American Association of Immunologists, Inc.

  4. B-Zell-Lymphome der Haut - Pathogenese, Diagnostik und Therapie.

    Science.gov (United States)

    Nicolay, Jan P; Wobser, Marion

    2016-12-01

    Primär kutane B-Zell-Lymphome (PCBCL) beschreiben reifzellige lymphoproliferative Erkrankungen der B-Zell-Reihe, die primär die Haut betreffen. Die Biologie und der klinische Verlauf der einzelnen PCBCL-Subtypen variieren untereinander stark und unterscheiden sich grundsätzlich von primär nodalen und systemischen B-Zell-Lymphomen. Primär kutane Marginalzonenlymphome (PCMZL) und primäre kutane follikuläre Keimzentrumslymphome (PCFCL) werden auf Grund ihres unkomplizierten Verlaufs und ihrer exzellenten Prognose zu den indolenten PCBCL gezählt. Demgegenüber stellen die diffus großzelligen B-Zell-Lymphome, hauptsächlich vom Beintyp (DLBCL, LT) die aggressiveren PCBCL-Varianten mit schlechterer Prognose dar. Für die Ausbreitungsdiagnostik und die Therapieentscheidung sind eine genaue histologische und immunhistochemische Klassifizierung sowie der Ausschluss einer systemischen Beteiligung in Abgrenzung zu nodalen oder systemischen Lymphomen notwendig. Die Diagnostik sollte dabei durch molekularbiologische Untersuchungen unterstützt werden. Therapeutisch stehen für die indolenten PCBCL primär operative und radioonkologische Maßnahmen im Vordergrund sowie eine Systemtherapie mit dem CD20-Antikörper Rituximab bei disseminiertem Befall. Die aggressiveren Varianten sollten in erster Linie mit Kombinationen aus Rituximab und Polychemotherapieschemata wie z. B. dem CHOP-Schema oder Modifikationen davon behandelt werden. Auf Grund der in allen seinen Einzelheiten noch nicht vollständig verstandenen Pathogenese und Biologie sowie des begrenzten Therapiespektrums der PCBCL besteht hier, speziell beim DLBCL, LT, noch erheblicher Forschungsbedarf. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  5. Non-invasive biomarkers and pulmonary function in smokers

    OpenAIRE

    Borrill, Zo? L; Roy, Kay; Vessey, Rupert S; Woodcock, Ashley A; Singh, Dave

    2008-01-01

    Zoë L Borrill1, Kay Roy1, Rupert S Vessey2, Ashley A Woodcock1, Dave Singh11Medicines Evaluation Unit, University of Manchester, Wythenshawe Hospital, Southmoor Rd, Manchester, UK; 2Glaxo Smith Kline, Philadelphia, USAAbstract: Limited information exists regarding measurement, reproducibility and interrelationships of non-invasive biomarkers in smokers. We compared exhaled breath condensate (EBC) leukotriene B4 (LTB4) and 8-isoprostane, exhaled nitric oxide, induced sputum, spirometr...

  6. Heat release from B4C oxidation in steam and air

    International Nuclear Information System (INIS)

    Belovsky, L.

    1996-01-01

    BWR and some PWR cores contain boron carbide (B 4 C) as neutron absorber. During a severe accident, the B 4 C can potentially react with steam under release of heat and hydrogen. Although models for B 4 C oxidation already exist in MELCOR and SCDAP/RELAP5, a development of a new model for another computer code seems to be difficult due to a missing comprehensive description of the current modelling methodology and scarce experimental data. The aim of this paper is to highlight the key points of the B 4 C oxidation using the existing available experimental data and to perform a simple heat balance analysis of the B 4 C/steam and B 4 C/air chemical reactions. The analysis of literature data shows that the B 4 C oxidation phenomenon is qualitatively well described below 1000 deg. C. However, no reliable data exist for the reaction kinetics especially above this temperature. It was found that the experimental results strongly depend on the experimental arrangement. The reaction heats, calculated in this study, indicate that the B 4 C oxidation is an exothermic reaction, releasing more heat in air than in steam. The formation of boric acids from the boron oxide increases the heat release from B 4 C by ∼ 10%, in the worst case. Although the total heat, released in a PWR core from the B 4 C oxidation, is probably much smaller than the heat released from the Zr/steam reaction, it is not excluded that the B 4 C oxidation can locally contribute to the damage of the control elements due to local overheating. Modelling of these phenomena is, however, very difficult due to the complex geometry of the liquefied control elements and due to absence of suitable data on the reaction kinetics. (author). 25 refs, 2 figs, 3 tabs

  7. Inhibition of Release of Vasoactive and Inflammatory Mediators in Airway and Vascular Tissues and Macrophages by a Chinese Herbal Medicine Formula for Allergic Rhinitis

    Directory of Open Access Journals (Sweden)

    George Binh Lenon

    2007-01-01

    Full Text Available Herbal therapies are being used increasingly for the treatment of allergic rhinitis. The aim of this study was to investigate the possible pharmacological actions and cellular targets of a Chinese herbal formula (RCM-101, which was previously shown to be effective in reducing seasonal allergic rhinitis symptoms in a randomized, placebo-controlled clinical trial. Rat and guinea pig isolated tissues (trachea and aorta were used to study the effects of RCM-101 on responses to various mediators. Production of leukotriene B4 in porcine neutrophils and of prostaglandin E2 and nitric oxide (NO in Raw 264.7 cells were also measured. In rat and guinea pig tracheal preparations, RCM-101 inhibited contractile responses to compound 48/80 but not those to histamine (guinea pig preparations or serotonin (rat preparations. Contractile responses of guinea pig tracheal preparations to carbachol and leukotriene C4, and relaxant responses to substance P and prostaglandin E2 were not affected by RCM-101. In rat aortic preparations, precontracted with phenylephrine, endothelium-dependent relaxant responses to acetylcholine and endothelium-independent relaxant responses to sodium nitroprusside were not affected by RCM-101. However, RCM-101 inhibited relaxations to l-arginine in endothelium-denuded rat aortic preparations, which had been pre-incubated with lipopolysaccharide. RCM-101 did not affect leukotriene B4 formation in isolated porcine neutrophils, induced by the calcium ionophore A23187; however, it inhibited prostaglandin E2 and NO production in lipopolysaccharide-stimulated murine macrophages (Raw 264.7 cells.The findings indicate that RCM-101 may have multiple inhibitory actions on the release and/or synthesis of inflammatory mediators involved in allergic rhinitis.

  8. Solid-State Synthesis and Structure of the Enigmatic Ammonium Octaborate: (NH4)2[B7O9(OH)5]·3/4B(OH)3·5/4H2O.

    Science.gov (United States)

    Neiner, Doinita; Sevryugina, Yulia V; Schubert, David M

    2016-09-06

    The compound known since the 19th century as ammonium octaborate was structurally characterized revealing the ammonium salt of the ribbon isomer of the heptaborate anion, [B7O9(OH)5](2-), with boric acid and water molecules. Of composition (NH4)2B7.75O12.63·4.88H2O, it approximates the classical ammonium octaborate composition (NH4)2B8O13·6H2O and has the structural formula {(NH4)2[B7O9(OH)5]}4·3B(OH)3·5H2O. It spontaneously forms at room temperature in solid-state mixtures of ammonium tetraborate and ammonium pentaborate. It crystallizes in the monoclinic space group P21/c with a = 11.4137(2) Å, b = 11.8877(2) Å, c = 23.4459(3) Å, β = 90.092(1)°, V = 3181.19(8) Å(3), and Z = 2 and contains well-ordered ammonium cations and [B7O9(OH)5](2-) anions and disordered B(OH)3 and H2O molecules linked by extensive H bonding. Expeditious solid-state formation of the heptaborate anion under ambient conditions has important implications for development of practical syntheses of industrially useful borates.

  9. Structure, chain conformation and antitumor activity of a novel polysaccharide from Lentinus edodes.

    Science.gov (United States)

    Yu, Zhang; Ming, Gu; Kaiping, Wang; Zhixiang, Chen; Liquan, Dai; Jingyu, Liu; Fang, Zeng

    2010-12-01

    A water-soluble polysaccharide LT1 was isolated from the basidiocarps of Lentinus edodes by hot water extraction and ethanol precipitations, further purified by gel chromatography. The Mw of LT1 was estimated to be 642 kDa by using HPGPC. Chemical and spectroscopic studies illustrated that LT1 has a backbone chain composed of 1 → 4-linked and 1 → 3-linked glucopyranosyl residues and has branches of single glucosyl stubs at C-6 of β-(1 → 4)-linked glucopyranosyl. AFM and Congo-red test revealed that LT1 existed as triple helix chain in 0.10 M NaOH solution or distilled water. Our studies showed that LT1 presented significant antitumor bioactivities on Sarcoma180 solid tumor cell implanted in BALB/c mice, which implies that LT1 could be potentially applied as a natural antitumor drug. Copyright © 2010 Elsevier B.V. All rights reserved.

  10. Improved Photovoltaic Performance of a Semicrystalline Narrow Bandgap Copolymer Based on 4H-Cyclopenta[2,1-b : 3,4-b ']dithiophene Donor and Thiazolo[5,4-d]thiazole Acceptor Units

    NARCIS (Netherlands)

    Van Mierloo, Sarah; Hadipour, Afshin; Spijkman, Mark-Jan; Van den Brande, Niko; Ruttens, Bart; Kesters, Jurgen; D'Haen, Jan; Van Assche, Guy; de Leeuw, Dago M.; Aernouts, Tom; Manca, Jean; Lutsen, Laurence; Vanderzande, Dirk J.; Maes, Wouter; Haen, Jan D’

    2012-01-01

    A solution processable narrow bandgap polymer composed of alternating 2,5-dithienylthiazolo[5,4-d]thiazole and asymmetrically alkyl-substituted 4H-cyclopenta[2,1-b:3,4-b']dithiophene units (PCPDT-DTTzTz) was synthesized by Suzuki polycondensation and the donor acceptor copolymer was thoroughly

  11. Thermoluminescence properties of Li2B4O7:Cu, B phosphor synthesized using solution combustion technique

    International Nuclear Information System (INIS)

    Ozdemir, A.; Altunal, V.; Kurt, K.; Depci, T.; Yu, Y.; Lawrence, Y.; Nur, N.; Guckan, V.; Yegingil, Z.

    2017-01-01

    To determine the effects of various concentrations of the activators copper (Cu) and boron (B) on the thermoluminescence (TL) properties of lithium tetraborate, the phosphor was first synthesized and doped with five different concentrations of copper (0.1–0.005 wt%) using solution combustion method. 0.01 wt% Cu was the concentration which showed the most significant increase in the sensitivity of the phosphor. The second sort of Li 2 B 4 O 7 :Cu material was prepared by adding B (0.001–0.03 wt%) to it. The newly developed copper-boron activated lithium tetraborate (Li 2 B 4 O 7 :Cu, B) material with 0.01 wt% Cu and 0.001 wt% B impurity concentrations was shown to have promise as a TL phosphor. The material formation was examined using powder x-Ray Diffraction (XRD) analysis and Scanning Electron Microscope (SEM) imaging. Fourier Transform Infrared (FT-IR) spectrum of the synthesized polycrystalline powder sample was also recorded. The TL glow curves were analyzed to determine various dosimetric characteristics of the synthesized luminophosphors. The dose response increased in a “linear” way with the beta-ray exposure between 0.1–20 Gy, a dose range being interested in medical dosimetry. The response with changing photon and electron energy was studied. The rate of decay of the TL signal was investigated both for dark storage and under direct sunlight. Li 2 B 4 O 7 :Cu, B showed no individual variation of response in 9 recycling measurements. The fluorescence spectrum was determined. The kinetic parameters were estimated by different methods and the results discussed. The studied properties of synthesized Li 2 B 4 O 7 :Cu, B were found all favorable for dosimetric purposes. - Highlights: • Li 2 B 4 O 7 :Cu, B synthesis using solution combustion method with various concentrations. • Structure analysis of Li 2 B 4 O 7 :Cu, B using XRD, SEM and FTIR methods. • Investigation of thermoluminescent properties of Li 2 B 4 O 7 :Cu, B. • Relatively good

  12. Effects of B4C control rod degradation under severe accident

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Si-Won; Park, Sang-Gil; Han, Sang-Ku [Atomic Creative Technology Co., Daejeon (Korea, Republic of)

    2016-10-15

    Boron carbide (B4C) is widely used as absorber material in western boiling water reactor (BWR), some PWR, EPR and Russian RBMK and VVERs. B4C oxidation is one of the important phenomena of in-vessel. In the present paper, the main results and knowledge gained regarding the B4C control rod degradation from above mentioned experiments are reviewed and arranged to inform its significance on the severe accident consequences. In this paper, the role of B4C control rod oxidation and the subsequent degradation on the severe accident consequences is reviewed with available literature and report of previous experimental program regarding the B4C oxidation. From this review, it seems that the contribution of this B4C oxidation on the accident progression to the further severe accident situation is not negligible. For the future work, the extensive experimental data interpretation will be performed to assess quantitatively the effect of B4C oxidation and degradation on the various postulated severe accident conditions.

  13. Rab5 Enhances Classical Swine Fever Virus Proliferation and Interacts with Viral NS4B Protein to Facilitate Formation of NS4B Related Complex

    Directory of Open Access Journals (Sweden)

    Jihui Lin

    2017-08-01

    Full Text Available Classical swine fever virus (CSFV is a fatal pig pestivirus and causes serious financial losses to the pig industry. CSFV NS4B protein is one of the most important viral replicase proteins. Rab5, a member of the small Rab GTPase family, is involved in infection and replication of numerous viruses including hepatitis C virus and dengue virus. Until now, the effects of Rab5 on the proliferation of CSFV are poorly defined. In the present study, we showed that Rab5 could enhance CSFV proliferation by utilizing lentivirus-mediated constitutive overexpression and eukaryotic plasmid transient overexpression approaches. On the other hand, lentivirus-mediated short hairpin RNA knockdown of Rab5 dramatically inhibited virus production. Co-immunoprecipitation, glutathione S-transferase pulldown and laser confocal microscopy assays further confirmed the interaction between Rab5 and CSFV NS4B protein. In addition, intracellular distribution of NS4B-Red presented many granular fluorescent signals (GFS in CSFV infected PK-15 cells. Inhibition of basal Rab5 function with Rab5 dominant negative mutant Rab5S34N resulted in disruption of the GFS. These results indicate that Rab5 plays a critical role in facilitating the formation of the NS4B related complexes. Furthermore, it was observed that NS4B co-localized with viral NS3 and NS5A proteins in the cytoplasm, suggesting that NS3 and NS5A might be components of the NS4B related complex. Taken together, these results demonstrate that Rab5 positively modulates CSFV propagation and interacts with NS4B protein to facilitate the NS4B related complexes formation.

  14. Metabolic safety-margins do not differ between cows of high and low genetic merit for milk production

    DEFF Research Database (Denmark)

    Knight, Christopher Harold; Alamer, Mohammed A; Sorensen, Annette

    2004-01-01

    Three galactopoietic stimuli, frequent milking (4X), bovine somatotrophin (bST) and thyroxine (T4) were used in an additive stair-step design to achieve maximum output (metabolic capacity) in six peak-lactation cows of high genetic merit (HT) and six of low genetic merit (LT). A further six of ea...... the commonly held belief that selective breeding of dairy cows for high milk production has rendered them markedly more susceptible to metabolic disturbances.......Three galactopoietic stimuli, frequent milking (4X), bovine somatotrophin (bST) and thyroxine (T4) were used in an additive stair-step design to achieve maximum output (metabolic capacity) in six peak-lactation cows of high genetic merit (HT) and six of low genetic merit (LT). A further six of each...... elevated heart rate and significant loss of body weight and condition compared with the combination of 4X and bST. As a result, treatments were discontinued, on an individual cow basis, before completion of this 6-week phase. Time on experiment did not differ between HT and LT. The results do not support...

  15. Sodium Hypochlorite-Modified Hemosorbents in the Treatment of Limb Ischemia-Reperfusion Syndrome: Experimental Study

    Directory of Open Access Journals (Sweden)

    V. I. Sergiyenko

    2007-01-01

    Full Text Available Objective: to enhance the efficiency of treatment for limb ischemia-reperfusion syndrome in an experiment, by using the modified hemosorbents that have oxidative properties.Materials and methods. The investigation was conducted on 94 mongrel male dogs divided into 3 groups: 1 intact animals (n=20; 2 animals treated with hemocarboperfusion on the standard sorbent CKH-1K (n=36; 3 animals received hemocarboperfusion on sodium hypochloride-modified sorbent CKH-1K (n=38. A model of acute ischemia-reperfusion syndrome was created by the method of V. D. Pasechnikov et al. Partial oxygen tension (pO2 was determined by pin polarography. The levels of vasoactive eicosanoids were measured by enzyme immunoassay.Results. In the animals with leg ischemia syndrome, there is a significant pO2 reduction in the muscles of the hip and shin, which does not completely recover after reperfusion. Standard CKN-1K sorbent hemocarboperfusion reduces pO2 as compared with the reperfusion period while the use of modified CKH-1K hemosorbent increased pO2 in the study hind limb muscles to the level observed in intact animals. The development of ischemia and reperfusion is accompanied by the elevated levels of inflammatory mediators that have vasoconstrictive properties (thromboxane B2, endothelin-1, leukotrienes C4/D4/E4 and the lower concentration of the vasodilator prostacyclin. Standard CKN-1K sorbent hemocarboperfusion results in a further increase in the concentrations of thromboxane B2 and leukotrienes C4/D4/E4, a decrease in the concentration of endothelin-1, and an elevation of the levels of prostacyclin and prostaglandin E2. When sodium hypochlorite-modified CKN-1K sorbent hemocarboperfusion is employed, the concentrations of thromboxane B2, endothelin-1, and leukotrienes C4/D4/E4 decrease, and the level of prostacyclin increases.Conclusion. Hemocarboperfusion used in the treatment of leg ischemia-reperfusion syndrome leads to restoration of tissue oxygenation and

  16. Rotational-mode component of the density of levels of nuclei with A approx-lt 150

    International Nuclear Information System (INIS)

    Rastopchin, E.M.; Svirin, M.I.; Smirenkin, G.N.

    1992-01-01

    Some difficulties which arise in the use of the generalized superfluid model to describe the density of levels in the region A approx-lt 150, as the result of an imperfect understanding of collective nuclear excitations, are discussed. One possible way to overcome these difficulties is examined. The idea is to depart from the conventional classification of collective nuclear properties and make use of small static deformations predicted theoretically and a corresponding rotational-mode component of the density of levels of these nuclei

  17. Improving containment mass and energy releases for CONTEMPT-LT/028 TU with RELAP5/MOD3

    International Nuclear Information System (INIS)

    DaSilva, H.C.; Choe, W.G.

    1996-01-01

    In order to obtain boundary conditions for RELAP5/MOD3 best estimate (BE) large break (LB) loss-of-coolant accident (LOCA) calculations, it is necessary to utilize a separate containment analysis code CONTEMPT-LT/028 TU, which in turn accepts mass and energy releases from the RELAP5/MOD3 calculation. When these boundary conditions are obtained, they are observed to be significantly lower than those reported in FSAR containment analyses. This motivates the present study, where RELAP5/MOD3 mass and energy releases are generated using the same assumptions listed in the FSAR containment calculations. Then CONTEMPT-LT/028 TU pressures and temperatures calculated with both sets of mass and energy releases are compared. It is seen that those obtained with the RELAP5/MOD3 input are still significantly lower, indicating a level of conservatism in the FSAR mass and energy releases that is even above that explicitly listed and also incorporated into the RELAP5/MOD3 calculation. An important conclusion from this finding is that Environmental Qualification (EQ) issues requiring containment re-analyses are likely to be easily resolved if new mass and energy releases are calculated with state-of-the-art LOCA codes modeling the entire reactor coolant system, even when conservative assumptions are incorporated

  18. Perpendicular magnetic anisotropy in Ta|Co40Fe40B20|MgAl2O4 structures and perpendicular CoFeB|MgAl2O4|CoFeB magnetic tunnel junction

    KAUST Repository

    Tao, B. S.

    2014-09-08

    Magnetic properties of Co40Fe40B20(CoFeB) thin films sandwiched between Ta and MgAl2O4layers have been systematically studied. For as-grown state, Ta/CoFeB/MgAl2O4structures exhibit good perpendicular magnetic anisotropy (PMA) with interface anisotropy Ki=1.22erg/cm2, which further increases to 1.30erg/cm2after annealing, while MgAl2O4/CoFeB/Ta multilayer shows in-plane magnetic anisotropy and must be annealed in order to achieve PMA. For bottom CoFeB layer, the thickness window for PMA is from 0.6 to 1.0nm, while that for top CoFeB layer is between 0.8 and 1.4nm. Perpendicular magnetic tunnel junctions (p-MTJs) with a core structure of CoFeB/MgAl2O4/CoFeB have also been fabricated and tunneling magnetoresistance ratio of about 36% at room temperature and 63% at low temperature have been obtained. The intrinsic excitations in the p-MTJs have been identified by inelastic electron-tunneling spectroscopy.

  19. Perpendicular magnetic anisotropy in Ta|Co40Fe40B20|MgAl2O4 structures and perpendicular CoFeB|MgAl2O4|CoFeB magnetic tunnel junction

    KAUST Repository

    Tao, B. S.; Li, D. L.; Yuan, Z. H.; Liu, H. F.; Ali, S. S.; Feng, J. F.; Wei, H. X.; Han, X. F.; Liu, Y.; Zhao, Y. G.; Zhang, Q.; Guo, Zaibing; Zhang, Xixiang

    2014-01-01

    Magnetic properties of Co40Fe40B20(CoFeB) thin films sandwiched between Ta and MgAl2O4layers have been systematically studied. For as-grown state, Ta/CoFeB/MgAl2O4structures exhibit good perpendicular magnetic anisotropy (PMA) with interface anisotropy Ki=1.22erg/cm2, which further increases to 1.30erg/cm2after annealing, while MgAl2O4/CoFeB/Ta multilayer shows in-plane magnetic anisotropy and must be annealed in order to achieve PMA. For bottom CoFeB layer, the thickness window for PMA is from 0.6 to 1.0nm, while that for top CoFeB layer is between 0.8 and 1.4nm. Perpendicular magnetic tunnel junctions (p-MTJs) with a core structure of CoFeB/MgAl2O4/CoFeB have also been fabricated and tunneling magnetoresistance ratio of about 36% at room temperature and 63% at low temperature have been obtained. The intrinsic excitations in the p-MTJs have been identified by inelastic electron-tunneling spectroscopy.

  20. On the Solution of the Rational Matrix Equation X=Q+LX−1LT

    Directory of Open Access Journals (Sweden)

    Heike Faßbender

    2007-01-01

    Full Text Available We study numerical methods for finding the maximal symmetric positive definite solution of the nonlinear matrix equation X=Q+LX−1LT, where Q is symmetric positive definite and L is nonsingular. Such equations arise for instance in the analysis of stationary Gaussian reciprocal processes over a finite interval. Its unique largest positive definite solution coincides with the unique positive definite solution of a related discrete-time algebraic Riccati equation (DARE. We discuss how to use the butterfly SZ algorithm to solve the DARE. This approach is compared to several fixed-point and doubling-type iterative methods suggested in the literature.

  1. 5-Methyl-4-oxo-4,6-dihydro-3H-pyridazino[4,5-b]carbazole-1-carbonitrile

    Directory of Open Access Journals (Sweden)

    Norbert Haider

    2010-02-01

    Full Text Available The title compound was prepared in excellent yield from 5-methyl-4-oxo-4,6-dihydro-3H-pyridazino[4,5-b]carbazole-1-carbaldehyde by treatment with hydroxylamine hydrochloride in formic acid without isolation of the intermediate oxime.

  2. Low temperature phase transition and crystal structure of CsMgPO{sub 4}

    Energy Technology Data Exchange (ETDEWEB)

    Orlova, Maria, E-mail: maria.p.orlova@gmail.com [Institute of Mineralogy and Petrography, University of Innsbruck, Innrain 52, Innsbruck 6020 (Austria); Khainakov, Sergey [Departamento de Química Física y Analítica, Universidad de Oviedo—CINN, 33006 Oviedo (Spain); Servicios Científico Técnicos, Universidad de Oviedo, 33006 Oviedo (Spain); Michailov, Dmitriy [Department of Chemistry, University of Nizhny Novgorod, 23 Gagarin av., Nizhny Novgorod 603950 (Russian Federation); Perfler, Lukas [Institute of Mineralogy and Petrography, University of Innsbruck, Innrain 52, Innsbruck 6020 (Austria); Langes, Christoph [Institute of Pharmacy, University of Innsbruck, Innrain 52, Innsbruck 6020 (Austria); Kahlenberg, Volker [Institute of Mineralogy and Petrography, University of Innsbruck, Innrain 52, Innsbruck 6020 (Austria); Orlova, Albina [Department of Chemistry, University of Nizhny Novgorod, 23 Gagarin av., Nizhny Novgorod 603950 (Russian Federation)

    2015-01-15

    CsMgPO{sub 4} doped with radioisotopes is a promising compound for usage as a radioactive medical source. However, a low temperature phase transition at temperatures close to ambient conditions (∼−40 °C) was observed. Information about such kind of structural changes is important in order to understand whether it can cause any problem for medical use of this compound. The phase transition has been investigated in detail using synchrotron powder diffraction, Raman spectroscopy and DFT calculations. The structure undergoes a transformation from an orthorhombic modification, space group Pnma (RT phase) to a monoclinic polymorph, space group P2{sub 1}/n (LT phase). New LT modification adopts similar to RT but slightly distorted unit cell: a=9.58199(2) Å, b=8.95501(1) Å, c=5.50344(2) Å, β=90.68583(1)°, V=472.198(3) Å{sup 3}. CsMgPO{sub 4} belongs to the group of framework compounds and is made up of strictly alternating MgO{sub 4}- and PO{sub 4}-tetrahedra sharing vertices. The cesium counter cations are located in the resulting channel-like cavities. Upon the transformation a combined tilting of the tetrahedra is observed. A comparison with other phase transitions in ABW-type framework compounds is given. - Graphical abstract: Structural behavior of β-tridymite-type phosphate CsMgPO{sub 4}, considered as potential chemical form for radioactive Cs-source has been studied at near ambient temperatures. A phase transition at (∼−40 °C) has been found and investigated. It has been established that the known orthorhombic RT modification, space group Pnma, adopts a monoclinic cell with space group P2{sub 1}/n at low temperatures. In this paper, we present results of structural analysis of changes accompanying this phase transition and discuss its possible impact on the application properties. - Highlights: • β-Tridymite type phosphate CsMgPO{sub 4} undergoes so called translationengleiche phase transition of index 2 at −40 °C. • The structure

  3. B7-H4 as a Target for Breast Cancer Immunotherapy

    Science.gov (United States)

    2013-06-01

    papain proteinase K pronase trypsin B7-H4R B """""" B7-H4R-APC CD25-FITC...Figure 5. B7-H4 receptor is protease resistant. Karpas 299 cells were treated with 0.3 mg/mL papain , 0.025 mg/mL proteinase K, 0.15 mg/mL pronase

  4. Clinical benefits of aspirin desensitization in patients with nonsteroidal anti-inflammatory drug exacerbated respiratory disease are not related to urinary eicosanoid release and are accompanied with decreased urine creatinine.

    Science.gov (United States)

    Makowska, Joanna S; Olszewska-Ziąber, Agnieszka; Bieńkiewicz, Barbara; Lewandowska-Polak, Anna; Kurowski, Marcin; Woźniakowski, Bartłomiej; Rotkiewicz, Arkadiusz; Kowalski, Marek L

    2016-05-01

    Treatment with acetylsalicylic acid (ASA) after desensitization may be a therapeutic option in patients with nonsteroidal anti-inflammatory drug exacerbated respiratory disease (NERD). The mechanisms that lead to improvement in rhinosinusitis and asthma symptoms remain unknown. To attribute the documented clinical effects of ASA treatment of chronic rhinosinusitis and/or asthma to the release of eicosanoid metabolites in urine. Fourteen patients with NERD were successfully desensitized, and, eventually, eight patients were treated with 650 mg of ASA daily for 3 months. In addition to clinical assessments, nuclear magnetic resonance imaging and smell test were performed before and after treatment with ASA. Venous blood and urine were collected before desensitization and after 1 and 3 months of treatment. The levels of urinary leukotrienes (LT) (cysteinyl LT and LTE4) and tetranor PGDM (metabolite of prostaglandin D2) were measured by enzyme-linked immunosorbent assay. Treatment with ASA after desensitization alleviated symptoms of rhinosinusitis, improved nasal patency (mean, 50% decrease in peak nasal inspiratory flow) and sense of smell (fourfold increase in smell test score) in as early as 4 weeks. Clinical improvements were not accompanied by any change in sinonasal mucosa thickness as assessed with nuclear magnetic resonance. Urinary cysteinyl LTs, LTE4, and prostaglandin D2 metabolite remained relatively stable during ASA treatment and did not correlate with clinical improvements. Desensitization was associated with a progressive decrease of urinary creatinine. Clinical improvement in rhinosinusitis and/or asthma after ASA desensitization was not related to concentrations of urinary eicosanoid metabolites. A decrease of urinary creatinine requires further study to determine the renal safety of long-term treatment with ASA after desensitization.

  5. The effect of rider weight and additional weight in Icelandic horses in tölt: part I. Physiological responses.

    Science.gov (United States)

    Stefánsdóttir, G J; Gunnarsson, V; Roepstorff, L; Ragnarsson, S; Jansson, A

    2017-09-01

    This study examined the effect of increasing BW ratio (BWR) between rider and horse, in the BWR range common for Icelandic horses (20% to 35%), on heart rate (HR), plasma lactate concentration (Lac), BWR at Lac 4 mmol/l (W4), breathing frequency (BF), rectal temperature (RT) and hematocrit (Hct) in Icelandic horses. In total, eight experienced school-horses were used in an incremental exercise test performed outdoors on an oval riding track and one rider rode all horses. The exercise test consisted of five phases (each 642 m) in tölt, a four-beat symmetrical gait, at a speed of 5.4±0.1 m/s (mean±SD), where BWR between rider (including saddle) and horse started at 20% (BWR20), was increased to 25% (BWR25), 30% (BWR30), and 35% (BWR35) and finally decreased to 20% (BWR20b). Between phases, the horses were stopped (~5.5 min) to add lead weights to specially adjusted saddle bags and a vest on the rider. Heart rate was measured during warm-up, the exercise test and after 5, 15 and 30 min of recovery and blood samples were taken and BF recorded at rest, and at end of each of these aforementioned occasions. Rectal temperature was measured at rest, at end of the exercise test and after a 30-min recovery period. Body size and body condition score (BCS) were registered and a clinical examination performed on the day before the test and for 2 days after. Heart rate and BF increased linearly (P0.05), but negative correlations (Phorses had no clinical remarks on palpation and at walk 1 and 2 days after the test. In conclusion, increasing BWR from 20% to 35% resulted in increased HR, Lac, RT and BF responses in the test group of experienced adult Icelandic riding horses. The horses mainly worked aerobically until BWR reached 22.7%, but considerable individual differences (17.0% to 27.5%) existed that were not linked to horse size, but to back BCS.

  6. Murid herpesvirus-4 exploits dendritic cells to infect B cells.

    Directory of Open Access Journals (Sweden)

    Miguel Gaspar

    2011-11-01

    Full Text Available Dendritic cells (DCs play a central role in initiating immune responses. Some persistent viruses infect DCs and can disrupt their functions in vitro. However, these viruses remain strongly immunogenic in vivo. Thus what role DC infection plays in the pathogenesis of persistent infections is unclear. Here we show that a persistent, B cell-tropic gamma-herpesvirus, Murid Herpesvirus-4 (MuHV-4, infects DCs early after host entry, before it establishes a substantial infection of B cells. DC-specific virus marking by cre-lox recombination revealed that a significant fraction of the virus latent in B cells had passed through a DC, and a virus attenuated for replication in DCs was impaired in B cell colonization. In vitro MuHV-4 dramatically altered the DC cytoskeleton, suggesting that it manipulates DC migration and shape in order to spread. MuHV-4 therefore uses DCs to colonize B cells.

  7. Popüler Kültür, Politika ve Din: Prime-Time ya da Selfie Dindarlığı/Popular Culture, Politics and Religion: Prime-Time or Selfie Religiosity

    Directory of Open Access Journals (Sweden)

    Ekmel Geçer

    2018-04-01

    Full Text Available Bu Popüler kültürü tanımlaması açısından anlamlı olan prime-time (altın saatler ve selfie (özçekim bağlamında, daha çok Türkiye örneğinde, dinin kitle iletişim mecralarındaki ve politik alandaki görünürlüğünü teorik bir değerlendirme vasıtasıyla ele alan bu çalışma; (a televizyon ekranlarında artan dindarlaşmanın sosyo-politik nedenlerini, (b popüler kültür ve reyting (izlenme oranı öğesi olarak din unsurunun etiğini, (c kamusal alanda sıklıkla kullanılan dini sembol ve söylemin davranışsal boyutunu ve (d “sosyal medya dindarlığı” olarak nitelendirilebilecek mobil iletişimdeki dindarlık biçimlerini analiz etmeyi amaçlamaktadır. Çalışmanın ilk sonuçları ve çözümlemeler, dini sembol ve söylemin, politik arena ve medya (yeni ve geleneksel mecralarında bir gösteri unsuru olarak kullanıldığını ve dinin popüler kültüre ait tüketilen bir öğeye dönüştüğüne işaret etmektedir. / This study, mostly in Turkish context, handling the religious scenes in mass communication and political sphere within the framework of two meaningful popular culture terms (prime-time and selfie, in theoretical terms and through unstructured observations, aims to analyse (a the socio-political reasons of increasing religiosity on television screens, (b the ethics of religious coverage as a popular culture or rating entry, (c the behavioural dimension of religious symbol or discourse that are much-applied in the public sphere and (d the forms of devotedness in mobile technologies which can be called as social media religiosity. The preliminary outcomes and the analysis of the article suggest that religious symbols and discourse have been used as a show-business in political arena and media courses (new and traditional and that religion has changed into a consumption item belonged to popular culture.

  8. B7-2 Expressed on EL4 Lymphoma Suppresses Antitumor Immunity by an Interleukin 4–dependent Mechanism

    OpenAIRE

    Stremmel, C.; Greenfield, E.A.; Howard, E.; Freeman, G.J.; Kuchroo, V.K.

    1999-01-01

    For T cells to become functionally activated they require at least two signals. The B7 costimulatory molecules B7-1 and B7-2 provide the “second signal” pivotal for T cell activation. In this report, we studied the relative roles of B7-1 and B7-2 molecules in the induction of antitumor immunity to the T cell thymoma, EL4. We generated EL4 tumor cells that expressed B7-1, B7-2, and B7-1+B7-2 by transfecting murine cDNAs. Our results demonstrate that EL4B7-1 cells are completely rejected in sy...

  9. A novel dioxygenation product of arachidonic acid possesses potent chemotactic activity for human polymorphonuclear leukocytes.

    Science.gov (United States)

    Shak, S; Perez, H D; Goldstein, I M

    1983-12-25

    We have found that a novel dioxygenation product of arachidonic acid, 8(S),15(S)-dihydroxy-5,11-cis-9,13-trans-eicosatetraenoic acid (8,15-diHETE), possesses chemotactic activity for human polymorphonuclear leukocytes comparable to that of leukotriene B4. Authentic 8,15-diHETE, identified by gas chromatography-mass spectrometry, was prepared by treating arachidonic acid with soybean lipoxygenase and was purified by reverse-phase high performance liquid chromatography. Using a "leading front" assay, 8,15-diHETE exhibited significant chemotactic activity at a concentration of 5.0 ng/ml. Maximum chemotactic activity was observed at a concentration of 30 ng/ml. The 8,15-diHETE generated by mixed human leukocytes after stimulation with arachidonic acid and the calcium ionophore, A23187, exhibited quantitatively similar chemotactic activity. Two synthetic all-trans conjugated isomers of 8,15-diHETE, however, were not chemotactic at concentrations up to 500 ng/ml. In contrast to its potent chemotactic activity, 8,15-diHETE (at concentrations up to 10 micrograms/ml) was relatively inactive with respect to its ability to provoke either degranulation or generation of superoxide anion radicals by cytochalasin B-treated leukocytes. Both leukotriene B4 and 8,15-diHETE may be important mediators of inflammation.

  10. B{sub 4}C thin films for neutron detection

    Energy Technology Data Exchange (ETDEWEB)

    Hoeglund, Carina [European Spallation Source ESS AB, P.O. Box 176, SE-221 00 Lund (Sweden); Department of Physics, Chemistry and Biology (IFM), Thin Film Physics Division, Linkoeping University, SE-581 83 Linkoeping (Sweden); Birch, Jens; Jensen, Jens; Hultman, Lars [Department of Physics, Chemistry and Biology (IFM), Thin Film Physics Division, Linkoeping University, SE-581 83 Linkoeping (Sweden); Andersen, Ken; Hall-Wilton, Richard [European Spallation Source ESS AB, P.O. Box 176, SE-221 00 Lund (Sweden); Bigault, Thierry; Buffet, Jean-Claude; Correa, Jonathan; Esch, Patrick van; Guerard, Bruno; Piscitelli, Francesco [Institute Laue Langevin, Rue Jules Horowitz, FR-380 00 Grenoble (France); Khaplanov, Anton [European Spallation Source ESS AB, P.O. Box 176, SE-221 00 Lund (Sweden); Institute Laue Langevin, Rue Jules Horowitz, FR-380 00 Grenoble (France); Vettier, Christian [European Spallation Source ESS AB, P.O. Box 176, SE-221 00 Lund (Sweden); European Synchrotron Radiation Facility, BP 220, FR-380 43 Grenoble Cedex 9 (France); Vollenberg, Wilhelmus [Vacuum, Surfaces and Coatings Group (TE/VSC), CERN, CH-1211 Geneva 23 (Switzerland)

    2012-05-15

    Due to the very limited availability of {sup 3}He, new kinds of neutron detectors, not based on {sup 3}He, are urgently needed. Here, we present a method to produce thin films of {sup 10}B{sub 4}C, with maximized detection efficiency, intended to be part of a new generation of large area neutron detectors. B{sub 4}C thin films have been deposited onto Al-blade and Si wafer substrates by dc magnetron sputtering from {sup nat}B{sub 4}C and {sup 10}B{sub 4}C targets in an Ar discharge, using an industrial deposition system. The films were characterized with scanning electron microscopy, elastic recoil detection analysis, x-ray reflectivity, and neutron radiography. We show that the film-substrate adhesion and film purity are improved by increased substrate temperature and deposition rate. A deposition rate of 3.8 A/s and substrate temperature of 400 deg. C result in films with a density close to bulk values and good adhesion to film thickness above 3 {mu}m. Boron-10 contents of almost 80 at. % are obtained in 6.3 m{sup 2} of 1 {mu}m thick {sup 10}B{sub 4}C thin films coated on Al-blades. Initial neutron absorption measurements agree with Monte Carlo simulations and show that the layer thickness, number of layers, neutron wavelength, and amount of impurities are determining factors. The study also shows the importance of having uniform layer thicknesses over large areas, which for a full-scale detector could be in total {approx}1000 m{sup 2} of two-side coated Al-blades with {approx}1 {mu}m thick {sup 10}B{sub 4}C films.

  11. A Novel Bifunctional Amino Acid Racemase With Multiple Substrate Specificity, MalY From Lactobacillus sakei LT-13: Genome-Based Identification and Enzymological Characterization

    Directory of Open Access Journals (Sweden)

    Shiro Kato

    2018-03-01

    Full Text Available The Lactobacillus sakei strain LK-145 isolated from Moto, a starter of sake, produces potentially large amounts of three D-amino acids, D-Ala, D-Glu, and D-Asp, in a medium containing amylase-digested rice as a carbon source. The comparison of metabolic pathways deduced from the complete genome sequence of strain LK-145 to the type culture strain of Lactobacillus sakei strain LT-13 showed that the L- and D-amino acid metabolic pathways are similar between the two strains. However, a marked difference was observed in the putative cysteine/methionine metabolic pathways of strain LK-145 and LT-13. The cystathionine β-lyase homolog gene malY was annotated only in the genome of strain LT-13. Cystathionine β-lyase is an important enzyme in the cysteine/methionine metabolic pathway that catalyzes the conversion of L-cystathionine into L-homocysteine. In addition to malY, most genome-sequenced strains of L. sakei including LT-13 lacked the homologous genes encoding other putative enzymes in this pathway. Accordingly, the cysteine/methionine metabolic pathway likely does not function well in almost all strains of L. sakei. We succeeded in cloning and expressing the malY gene from strain LT-13 (Ls-malY in the cells of Escherichia coli BL21 (DE3 and characterized the enzymological properties of Ls-MalY. Spectral analysis of purified Ls-MalY showed that Ls-MalY contained a pyridoxal 5′-phosphate (PLP as a cofactor, and this observation agreed well with the prediction based on its primary structure. Ls-MalY showed amino acid racemase activity and cystathionine β-lyase activity. Ls-MalY showed amino acid racemase activities in various amino acids, such as Ala, Arg, Asn, Glu, Gln, His, Leu, Lys, Met, Ser, Thr, Trp, and Val. Mutational analysis revealed that the -amino group of Lys233 in the primary structure of Ls-MalY likely bound to PLP, and Lys233 was an essential residue for Ls-MalY to catalyze both the amino acid racemase and β-lyase reactions. In

  12. Crystal structure of PrRh4.8B2

    International Nuclear Information System (INIS)

    Higashi, Iwami; Shishido, Toetsu; Takei, Humihiko; Kobayashi, Takaaki

    1988-01-01

    The crystal structure of a new rare earth ternary boride PrRh 4.8 B 2 was investigated, by single-crystal X-ray diffractometry. PrRh 4.8 B 2 crystallizes in the orthorhombic space group Immm with a = 9.697(4), b = 5.577(2), c = 25.64(3) A, Z=12. The intensity data were collected on a four-circle diffractometer with graphite-monochromatized Mo Kα radiation. The structure was solved by the Patterson method and refined with a full-matrix least-squares program to an R value (equal to Σvertical strokeΔFvertical stroke/Σvertical strokeF 0 vertical stroke) of 0.055 for 1176 reflections. (orig.)

  13. A Pilot Study: Effects of Dietary Supplementation with α-Linolenic Acid-Enriched Perilla Seed Oil on Bronchial Asthma

    Directory of Open Access Journals (Sweden)

    Kozo Ashida

    1997-01-01

    Full Text Available N-3 fatty acids, such as fish oil, have been reported to have some beneficial effects in patients with bronchial asthma. The effects of dietary supplementation with perilla seed oil rich in a-linolenic acid (α-LNA, parent n-3 fatty acid, were studied in five patients with asthma. The symptoms of asthma and mean peak flow rates (PFR both early in the morning and in the evening were improved 2 weeks after dietary supplementation and the increases in PFR were significant (P<0.05. The generation of leukotriene B4 (LTB4 by peripheral leukocytes stimulated with the Ca2+ ionophore A23187 was significantly suppressed from 77.6 to 41.6 ng/5Xl06 cells by dietary supplementation (P<0.05. The generation of leukotriene C4 (LTC4 by leukocytes was also significantly suppressed from 64.0 to 38.8 ng/5x106 cells after supplementation with perilla seed oil (P<0.05. These results suggest that dietary supplementation with perilla seed oil is beneficial for the treatment of asthma.

  14. Discovery of Dengue Virus NS4B Inhibitors

    Science.gov (United States)

    Wang, Qing-Yin; Dong, Hongping; Zou, Bin; Karuna, Ratna; Wan, Kah Fei; Zou, Jing; Susila, Agatha; Yip, Andy; Shan, Chao; Yeo, Kim Long; Xu, Haoying; Ding, Mei; Chan, Wai Ling; Gu, Feng; Seah, Peck Gee; Liu, Wei; Lakshminarayana, Suresh B.; Kang, CongBao; Lescar, Julien; Blasco, Francesca; Smith, Paul W.

    2015-01-01

    ABSTRACT The four serotypes of dengue virus (DENV-1 to -4) represent the most prevalent mosquito-borne viral pathogens in humans. No clinically approved vaccine or antiviral is currently available for DENV. Here we report a spiropyrazolopyridone compound that potently inhibits DENV both in vitro and in vivo. The inhibitor was identified through screening of a 1.8-million-compound library by using a DENV-2 replicon assay. The compound selectively inhibits DENV-2 and -3 (50% effective concentration [EC50], 10 to 80 nM) but not DENV-1 and -4 (EC50, >20 μM). Resistance analysis showed that a mutation at amino acid 63 of DENV-2 NS4B (a nonenzymatic transmembrane protein and a component of the viral replication complex) could confer resistance to compound inhibition. Genetic studies demonstrate that variations at amino acid 63 of viral NS4B are responsible for the selective inhibition of DENV-2 and -3. Medicinal chemistry improved the physicochemical properties of the initial “hit” (compound 1), leading to compound 14a, which has good in vivo pharmacokinetics. Treatment of DENV-2-infected AG129 mice with compound 14a suppressed viremia, even when the treatment started after viral infection. The results have proven the concept that inhibitors of NS4B could potentially be developed for clinical treatment of DENV infection. Compound 14a represents a potential preclinical candidate for treatment of DENV-2- and -3-infected patients. IMPORTANCE Dengue virus (DENV) threatens up to 2.5 billion people and is now spreading in many regions in the world where it was not previously endemic. While there are several promising vaccine candidates in clinical trials, approved vaccines or antivirals are not yet available. Here we describe the identification and characterization of a spiropyrazolopyridone as a novel inhibitor of DENV by targeting the viral NS4B protein. The compound potently inhibits two of the four serotypes of DENV (DENV-2 and -3) both in vitro and in vivo. Our

  15. Comparison of microstructural and mechanical properties of Al–TiC, Al–B4C and Al–TiC–B4C composites prepared by casting techniques

    International Nuclear Information System (INIS)

    Mazaheri, Y.; Meratian, M.; Emadi, R.; Najarian, A.R.

    2013-01-01

    In the present work, production of Al–10%TiC, Al–10% B 4 C, Al–5%TiC–5%B 4 C (volume fraction) composites by casting techniques were studied. However, casting techniques suffers from poor incorporation and distribution of the reinforcement particles in the matrix. These problems become especially significant as the reinforcement size decreases due to greater agglomeration tendency and reduced wettability of the particles with the melt. Microstructure characterization of the composite samples was investigated by using scanning electron microscopy (SEM) equipped with energy dispersive spectroscopy (EDS) and X-ray diffractometer (XRD).The results showed heat treatment of B 4 C particles and addition of TiC particles with the flux improved the wettability and incorporation of reinforcement particles into melt. Mechanical characterization of samples showed that maximum hardness had belonged to Al–5%TiC–5%B 4 C composite, maximum yield and tensile strength had belonged to Al–10%B 4 C composite and maximum elongation had belonged to Al–10%TiC composite. Furthermore, wear properties of composites revealed the better behavior for Al–B 4 C composite.

  16. Depleted Reactor Analysis With MCNP-4B

    International Nuclear Information System (INIS)

    Caner, M.; Silverman, L.; Bettan, M.

    2004-01-01

    Monte Carlo neutronics calculations are mostly done for fresh reactor cores. There is today an ongoing activity in the development of Monte Carlo plus burnup code systems made possible by the fast gains in computer processor speeds. In this work we investigate the use of MCNP-4B for the calculation of a depleted core of the Soreq reactor (IRR-1). The number densities as function of burnup were taken from the WIMS-D/4 cell code calculations. This particular code coupling has been implemented before. The Monte Carlo code MCNP-4B calculates the coupled transport of neutrons and photons for complicated geometries. We have done neutronics calculations of the IRR-1 core with the WIMS and CITATION codes in the past Also, we have developed an MCNP model of the IRR-1 standard fuel for a criticality safety calculation of a spent fuel storage pool

  17. Temperature dependence of the ESR linewidth in the paramagnetic phase (T{gt}T{sub C}) of R{sub 1{minus}x}B{sub x}MnO{sub 3+{delta}} (R=La,Pr; B=Ca,Sr)

    Energy Technology Data Exchange (ETDEWEB)

    Rettori, C.; Rao, D.; Singley, J.; Kidwell, D.; Oseroff, S.B. [San Diego State University, San Diego, California 92182 (United States); Causa, M.T. [Centro Atomico Bariloche and Instituto Balseiro 8400, San Carlos de Bariloche (Argentina); Neumeier, J.J.; McClellan, K.J. [Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States); Cheong, S. [ATT Bell Laboratories, Murray Hill, New Jersey 07974 (United States); Schultz, S. [University of California, San Diego, California 92037 (United States)

    1997-02-01

    Electron spin resonance (ESR) experiments in the paramagnetic phase of R{sub 1{minus}x}B{sub x}MnO{sub 3+{delta}} (R=La,Pr; B=Ca,Sr) show, for 1.1 T{sub C}{approx_lt}T{approx_lt}2T{sub C}, a linear T increase of the resonance linewidth, {Delta}H, in powders, ceramic pellets, and single crystals. Above {approximately}2T{sub C} a slowdown in the T increase of {Delta}H is observed. The data resemble the results found in other ferromagnetic insulators where the spin-lattice relaxation involves a single-phonon process. We find that the one-phonon process may account for the linear T dependence of the linewidth observed up to {approximately}2T{sub C}. A large T dependence of the resonance intensity above T{sub C} was found in all the samples studied, suggesting the existence of {ital spin clusters} in these compounds over a wide range of temperature. {copyright} {ital 1997} {ital The American Physical Society}

  18. Production of thermoluminescent dosemeters based on MgB{sub 4}O{sub 7}: Dy and MgB{sub 4}O{sub 7}: Tm; Producao de dosimetros termoluminescentes a base de MgB{sub 4}O{sub 7}: Dy e MgB{sub 4}O{sub 7}: Tm

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Luiza Freire de; Souza, Divanizia N., E-mail: luizaf25@hotmail.com, E-mail: divanizi@ufs.br [Universidade Federal de Sergipe (UFS), Sao Cristovao, SE (Brazil). Programa de Pos-Graduacao em Fisica

    2013-07-01

    The thermoluminescent dosimetry (TL) is a well-established technique for the detection of ionizing radiation in hospitals, clinics, and industrial establishments where there is the need to quantify the radiation. For this practice is require the use phosphors which are sensitive to radiation. Some phosphors are already commonly used in this practice, for example, TLD-100 (LiF: Mg, Ti), CaSO{sub 4}:Tm and CaSO{sub 4}:Dy. A compound that was most recently introduced in dosimetry and has many advantageous features to detect neutrons, electrons and gamma is the magnesium tetraborate (MgB{sub 4}O{sub 7}), but the undoped material is not good for dosimetry, since signal does not show satisfactory thermoluminescence. The present work presents the analysis of the compound MgB{sub 4}O{sub 7} when doped with rare earth elements, thulium (Tm) and dysprosium (Dy). The production of MgB{sub 4}O{sub 7}: Dy and MgB{sub 4}O{sub 7}: Tm occurred under acidic conditions. Following the process of crystal growth, several tests were made on phosphors produced to verify the quality of materials as TL dosimeter. Initially, was made the identification of the crystalline phases found in the material, using the technique of X-ray diffractometry, and then were evaluated and compared the TL emission curves of the crystals with two different types of dopants, to this, the samples were irradiated with different radiation sources: {sup 137}Cs (0,66 MeV), {sup 60}Co (1.25 MeV) and X-rays (0.41 MeV) and based on the results was evaluated the energy dependence of phosphors. Another characteristic analyzed, was the decay of TL signal for the material (fading). The results show that the material can be an excellent TL dosimeter when doped with rare earth elements Dy and Tm. (author)

  19. Performance enhancement of NdFeB nanoflakes prepared by surfactant-assisted ball milling at low temperature by using different surfactants

    Science.gov (United States)

    An, Xiaoxin; Jin, Kunpeng; Wang, Fang; Fang, Qiuli; Du, Juan; Xia, Weixing; Yan, Aru; Liu, J. Ping; Zhang, Jian

    2017-02-01

    Hard magnetic NdFeB submicron and nanoflakes were successfully prepared by surfactant-assisted ball milling at room temperature (SABMRT) and low temperature (SABMLT) by using oleic acid (OA), oleylamine (OLA) and trioctylamine (TOA) as surfactant, respectively. Among the surfactants used, OA and OLA have similar effects on the morphology of the NdFeB nanoflakes milled at both room and low temperature. In the case of TOA, irregular micron-sized particles and submirco/nanoflakes were obtained for the NdFeB powders prepared by SABMRT and SABMLT, respectively. Samples prepared by SABMLT show better crystallinity and better degree of grain alignment than that prepared by SABMRT with the same surfactant. Comparing with the samples milled at RT, higher coercivity and larger remanence ratio were achieved in the NdFeB samples prepared at LT. The amounts of residual surfactants in final NdFeB powders were also calculated, which reveals that the final NdFeB powders milled at LT possess lower amount of residual surfactants than those milled at RT. It was found that lowering milling temperature of SABM would be a promising way for fabricating permanent magnetic materials with better hard magnetic properties.

  20. Could the multicomponent meningococcal serogroup B vaccine (4CMenB) control Neisseria meningitidis capsular group X outbreaks in Africa?

    Science.gov (United States)

    Hong, Eva; Giuliani, Marzia Monica; Deghmane, Ala-Eddine; Comanducci, Maurizio; Brunelli, Brunella; Dull, Peter; Pizza, Mariagrazia; Taha, Muhamed-Kheir

    2013-02-04

    A new vaccine, 4CMenB, is composed of surface proteins of Neisseria meningitidis and is aimed to target serogroup B (MenB) isolates. The vaccine components are present in meningococcal isolates of other serogroups allowing potential use against meningococcal isolates belonging to non-B serogroups. Isolates of serogroup X (MenX) have been emerged in countries of the African meningitis belt. 4CMenB may offer a vaccine strategy against these isolates as there is no available capsule-based vaccine against MenX. We used the Meningococcal Antigen Typing System (MATS) to determine presence, diversity and levels of expression of 4CMenB antigens among 9 MenX isolates from several African countries in order to estimate the potential coverage of MenX by the 4CMenB vaccine. We performed bactericidal assays against these isolates, using pooled sera from 4CMenB-vaccinated infants, adolescents and adults. The African MenX isolates belonged to the same genotype but showed variation in the vaccine antigens. MATS data and bactericidal assays suggest coverage of the 9 African MenX isolates by 4CMenB but not of two unrelated MenX isolates from France. 4CMenB vaccine can be considered for further investigation to control MenX outbreaks in Africa. Copyright © 2012 Elsevier Ltd. All rights reserved.