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Sample records for thromboxane a2 modulates

  1. Kinetics of prostaglandin E2 and thromboxane A2 synthesis and suppression of PHA-stimulated peripheral blood mononuclear leucocytes.

    Science.gov (United States)

    Awara, W; Hillier, K; Jones, D

    1986-12-01

    The immunomodulatory effects of thromboxane A2 and prostaglandin E2 on peripheral blood mononuclear leucocytes stimulated with PHA in vitro, and the relationship of this to the time-course of their synthesis in culture, were investigated using prostaglandin E2, a thromboxane A2 synthesis inhibitor (UK37248), a thromboxane A2 mimic (U46619) and a thromboxane A2 receptor blocker (EP045). The inhibitory effect of prostaglandin E2 on PHA-induced human peripheral blood mononuclear leucocyte proliferation diminishes if the addition of PGE2 is delayed. If added 4 hr after a maximum concentration of PHA (5 micrograms/ml), the effect of PGE2 was reduced by 60%. If a submaximal concentration of PHA (1 microgram/ml) was used, the effect of PGE2 was not reduced if added 4 hr later but fell by about 60% after 16 hr. UK37248 moderately inhibited PHA-induced activation while substantially inhibiting thromboxane A2 synthesis and simultaneously enhancing PGE2 synthesis. The enhanced accumulation of PGE2 occurs while sensitivity to PGE2 is dropping. U46619, exogenously applied as a thromboxane A2 mimic, inhibited PHA-induced activation at concentrations that did not significantly alter PGE2 synthesis. EP045, which may modulate the effects of endogenous thromboxane A2 by blocking receptors, did not alter PHA-induced activation. We conclude that thromboxane A2 may have a role in inhibiting PHA-induced activation on the basis of the effect of U46619. However, this study highlights difficulties in utilizing prostaglandin and thromboxane receptor and synthesis inhibitors to examine their endogenous role in the modulation of mitogen-induced activation in vitro. If sensitivity to the purported endogenous substance is limited to the early stages of culture and if only low levels are synthesized at this early stage, then blocking drugs would have little effect.

  2. Thromboxane A2 increases endothelial permeability through upregulation of interleukin-8

    International Nuclear Information System (INIS)

    Kim, Su-Ryun; Bae, Soo-Kyung; Park, Hyun-Joo; Kim, Mi-Kyoung; Kim, Koanhoi; Park, Shi-Young; Jang, Hye-Ock; Yun, Il; Kim, Yung-Jin; Yoo, Mi-Ae; Bae, Moon-Kyoung

    2010-01-01

    Thromboxane A 2 (TXA 2 ), a major prostanoid formed from prostaglandin H 2 by thromboxane synthase, is involved in the pathogenesis of a variety of vascular diseases. In this study, we report that TXA 2 mimetic U46619 significantly increases the endothelial permeability both in vitro and in vivo. U46619 enhanced the expression and secretion of interleukin-8 (IL-8), a major inducer of vascular permeability, in endothelial cells. Promoter analysis showed that the U46619-induced expression of IL-8 was mainly regulated by nuclear factor-κB (NF-κB). U46619 induced the activation of NF-κB through IκB kinase (IKK) activation, IκB phosphorylation and NF-κB nuclear translocation. Furthermore, the inhibition of IL-8 or blockade of the IL-8 receptor attenuated the U46619-induced endothelial cell permeability by modulating the cell-cell junctions. Overall, these results suggest that U46619 promotes vascular permeability through the production of IL-8 via NF-κB activation in endothelial cells.

  3. Subarachnoid hemorrhage induces enhanced expression of thromboxane A2 receptors in rat cerebral arteries

    DEFF Research Database (Denmark)

    Ansar, Saema; Larsen, Carl; Maddahi, Aida

    2010-01-01

    Cerebral ischemia remains the key cause of morbidity and mortality after subarachnoid hemorrhage (SAH) with a pathogenesis that is still poorly understood. The aim of the present study was to examine the involvement of thromboxane A(2) receptors (TP) in the pathophysiology of cerebral ischemia...

  4. Characterization of a thromboxane A2/prostaglandin H2 receptor in guinea pig lung membranes using a radioiodinated thromboxane mimetic

    International Nuclear Information System (INIS)

    Saussy, D.L. Jr.; Mais, D.E.; Dube, G.P.; Magee, D.E.; Brune, K.A.; Kurtz, W.L.; Williams, C.M.

    1991-01-01

    Thromboxane A2 (TXA2) and prostaglandin H2 (PGH2) are potent constrictors of airway smooth muscle and may mediate some of the pulmonary effects of leukotrienes. To date, the TXA2/PGH2 receptor in lung has not been well characterized. In this report, we describe the evaluation of the TXA2/PGH2 receptor in guinea pig lung membranes using the new radiolabeled TXA2 mimetic [1S(1 alpha,2 beta(5Z),3 alpha(1E,3S*),4 alpha)]-7-[3-(3-hydroxy-4-(4'- iodophenoxy)-1-butenyl)-7-oxabicyclo-[2.2.1]heptan-2-yl]-5-h eptenoic acid (IBOP). IBOP elicited a dose-dependent contraction of guinea pig lung parenchymal strips (EC50 = 3.03 +/- 0.97 nM, three experiments), which was blocked by the TXA2/PGH2 antagonists SQ29548 (pKB = 7.44 +/- 0.2, three experiments), BM13505 (pKB = 6.29 +/- 0.26, three experiments), and I-PTA-OH (pKB = 5.82 +/- 0.36, three experiments). In radioligand binding studies, the binding of [125I]IBOP to guinea pig lung membranes prepared from perfused lungs was saturable, displaceable, and dependent upon protein concentration. Binding was optimal at pH 6.5 and was enhanced by the addition of mono- and divalent cations. The standard assay buffer was 25 mM 3-(N-morpholino)propanesulfonic acid, pH 6.5, 100 mM NaCl, 5 mM MgCl2. Binding was inhibited by pretreatment with dithiothreitol, N-ethylmaleimide, or beta-mercaptoethanol. Binding was unaffected by the addition of guanine nucleotide analogs at concentrations up to 300 microM. Analysis of the time course of binding of [125]IBOP at 30 degrees yielded k-1 = 0.0447 min-1, k1 = 2.49 x 10(8) M-1 min-1, and Kd = k-1/k1 = 180 pM. Computer analysis of equilibrium binding studies using nonlinear methods (LUNDON-1) revealed a single class of noninteracting binding sites with a Kd of 86.9 +/- 11.9 pM and a Bmax of 81.8 +/- 7.7 fmol/mg of protein (three experiments)

  5. Equol is more active than soy isoflavone itself to compete for binding to thromboxane A(2) receptor in human platelets.

    Science.gov (United States)

    Muñoz, Yenny; Garrido, Argelia; Valladares, Luis

    2009-03-01

    Several dietary intervention studies examining the health effect of soy isoflavones allude to the importance of equol in establishing the cardiovascular response to soy protein. Although, the specific mechanism by which this action occurs has not been established. The aim of this study was to investigate the inhibitory effect of soy-isoflavones and the metabolite of daidzein, equol, on agonist-induced platelet responses dependent on thromboxane A(2) (TxA(2)) receptor. Competitive radioligand binding assay was used to screen for affinity of these compounds to the TxA(2) receptor. The effect of equol on platelet activation, evaluate through of release of the ATP, by analogs of TxA(2) was analyzed. The effect of equol on platelet aggregation was investigated with ADP, U46619 (a TxA(2) mimic) and the calcium ionophore A23187. The data showed that aglycone isoflavones and equol bind to TxA(2) receptor in the micromol/L range, whereas their glucoside derivates had very low binding activity for this receptor. Under equilibrium conditions, the following order of the relative affinity in inhibiting [(3)H]-SQ29585 binding was: equol>genistein>daidzein>glycitein>genistin, daidzin, glycitin. Equol interaction was reversible and competitive for labeled-SQ29548 with not apparent decrease in the number of TxA(2) binding sites. In addition, from platelet activation studies, equol effectively inhibited ATP secretion elicited by the TxA(2) analog U46619. On the other hand, equol inhibited the platelet aggregation induced by U46619 and A23187, while it failed to inhibit that induced by ADP. The aglycone isoflavones from soy, and particularly equol, have been found to have biological effects attributable to thromboxane A(2) receptor antagonism. These findings may help elucidate how dietary isoflavone modulate platelet function and explain why soy-rich foods are claimed to have beneficial effects in the prevention of thrombotic events.

  6. Regulation of the tumor suppressor FOXO3 by the thromboxane-A2 receptors in urothelial cancer.

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    Philip M Sobolesky

    Full Text Available The transcription factor FOXO3 is a well-established tumor suppressor whose activity, stability, and localization are regulated by phosphorylation and acetylation. Previous data by our laboratory demonstrated amplified thromboxane-A2 signaling was associated with poor prognoses in bladder cancer patients and overexpression of the thromboxane-A2 isoform-β receptor (TPβ, but not TPα, induced malignant transformation of immortalized bladder cells in vivo. Here, we describe a mechanism of TP mediated modulation of FOXO3 activity and localization by phosphorylation and deacetylation in a bladder cancer cell model. In vitro gain and loss of function studies performed in non-transformed cell lines, UROsta and SV-HUC, revealed knockdown of FOXO3 expression by shRNA increased cell migration and invasion, while exogenously overexpressing TPβ raised basal phosphorylated (pFOXO3-S294 levels. Conversely, overexpression of ERK-resistant, mutant FOXO3 reduced increases in UMUC3 cell migration and invasion, including that mediated by TP agonist (U46619. Additionally, stimulation of UMUC3 cells with U46619 increased pFOXO3-S294 expression, which could be attenuated by treatment with a TP antagonist (PTXA2 or ERK inhibitor (U0126. Initially U46619 caused nuclear accumulation of pFOXO3-S294; however, prolonged stimulation increased FOXO3 cytoplasmic localization. U46619 stimulation decreased overall FOXO3 transcriptional activity, but was associated with increased expression of its pro-survival target, manganese superoxide dismutase. The data also shows that TP stimulation increased the expression of the histone deacetylase, SIRT1, and corresponded with decreased acetylated-FOXO3. Collectively, the data suggest a role for TP signaling in the regulation of FOXO3 activity, mediated in part through phosphorylation and deacetylation.

  7. Radioiodsodestannylation. Convenient synthesis of a high affinity thromboxane A2/prostaglandin H2 receptor antagonist

    International Nuclear Information System (INIS)

    Mais, D.E.; Hamanaka, Nobuyuki

    1991-01-01

    Radioiodination of methyl-7-[(2R, 2S, 5R)-6,6-dimethyl-3-(4-trimethylstannylbenzenesulfononylamino3S) bicyclo[3.1.1]hept-2-yl]-5(Z)-heptenoate with [ 125 I] Na using a modification of the chloramine-T method in organic solvent is simple with high yields and site specific. The product, following hydrolysis of the ester, 7-[(2R, 2S, 3S, 5R)-6,6-dimethyl-3-(4[ 125 I]-iodobenzenesulfonylamino) bicyclo[3.1.1]hept-2-yl]-5(Z)-heptenoic acid [( 125 I]-ISAP), was purified by HPLC. The high specific activity and specific binding will make the ligand a useful tool for the characterization of thromboxane A 2 /prostaglandin H 2 receptors. (author)

  8. Identification and characterization of a putative human platelet thromboxane A2/prostaglandin H2 receptor

    International Nuclear Information System (INIS)

    Saussy, D.L. Jr.

    1986-01-01

    The thromboxane A 2 (TXA 2 ) analog, 9,11-dimethylmethano-11,12-methano-16-(3-iodo-4-hydroxyphenyl)-13,14-dihydro-13-aza-15αβ-omega-tetranor TXA 2 (I-PTA-OH) was characterized as a competitive antagonist of TXA 2 mimetic-induced platelet aggregation, with a K/sub d/ of 190 nM in platelet rich plasma. This antagonism was specific for the putative thromboxane A 2 /prostaglandin H 2 (TXA 2 /PGH 2 ) receptor, since I-PTA-OH had no inhibitory effects on platelet aggregation stimulated by agonists which act independently of TXA 2 /PGH 2 , and did not inhibit platelet TXA 2 synthesis. [ 125 I]-PTA-OH binding to a particulate fraction from human platelets was saturable, displaceable, and linear with protein concentration. Scatchard analysis of equilibrium binding revealed a single class of high affinity binding sites, with a K/sub d/ of 30 +/- 4 nM and a B/sub max/ of 1.8 +/- 0.3 pmol/mg protein. Kinetic analysis yielded a k 1 of 1.35 x 10 6 M -1 x min -1 and a k√ 1 of 0.032 min -1 , K/sub d/ = k√ 1 /k 1 = 24 nM. The subcellular localization of the putative TXA 2 /PGH 2 receptor was determined using [ 125 I]-PTA-OH binding as a marker for the receptor. [ 125 I]-PTA-OH binding as a marker for the receptor. [ 125 I]-PTA-OH binding, was coenriched with markers for plasma membranes and dense tubular system; but not with markers for cytoplasmic constituents, mitochondria, or granules

  9. Inverse agonism of SQ 29,548 and Ramatroban on Thromboxane A2 receptor.

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    Raja Chakraborty

    Full Text Available G protein-coupled receptors (GPCRs show some level of basal activity even in the absence of an agonist, a phenomenon referred to as constitutive activity. Such constitutive activity in GPCRs is known to have important pathophysiological roles in human disease. The thromboxane A2 receptor (TP is a GPCR that promotes thrombosis in response to binding of the prostanoid, thromboxane A2. TP dysfunction is widely implicated in pathophysiological conditions such as bleeding disorders, hypertension and cardiovascular disease. Recently, we reported the characterization of a few constitutively active mutants (CAMs in TP, including a genetic variant A160T. Using these CAMs as reporters, we now test the inverse agonist properties of known antagonists of TP, SQ 29,548, Ramatroban, L-670596 and Diclofenac, in HEK293T cells. Interestingly, SQ 29,548 reduced the basal activity of both, WT-TP and the CAMs while Ramatroban was able to reduce the basal activity of only the CAMs. Diclofenac and L-670596 showed no statistically significant reduction in basal activity of WT-TP or CAMs. To investigate the role of these compounds on human platelet function, we tested their effects on human megakaryocyte based system for platelet activation. Both SQ 29,548 and Ramatroban reduced the platelet hyperactivity of the A160T genetic variant. Taken together, our results suggest that SQ 29,548 and Ramatroban are inverse agonists for TP, whereas, L-670596 and Diclofenac are neutral antagonists. Our findings have important therapeutic applications in the treatment of TP mediated pathophysiological conditions.

  10. Effects of heparin on platelet aggregation and release and thromboxane A2 production

    International Nuclear Information System (INIS)

    Mohammad, S.F.; Anderson, W.H.; Smith, J.B.; Chuang, H.Y.; Mason, R.G.

    1981-01-01

    Heparin, when added to citrated platelet-rich plasma (PRP), caused potentiation of platelet aggregation and the release reaction induced by the aggregating agents adenosine diphosphate (ADP), arachidonic acid, collagen, and epinephrine. At low concentrations (4.7 x 10(-5) M) arachidonic acid failed to cause aggregation of platelets in citrated PRP. However, in the presence of heparin, the same concentration of arachidonic acid caused aggregation. Examination of PRP for the presence of thromboxane A2 (TxA2) by use of a bioassay revealed that heparin also stimulated release of TxA2. This finding indicated that platelets released more TxA2 when they were challenged by low concentrations of arachidonic acid in the presence of heparin than in its absence. Platelets were labeled with 3 H-arachidonic acid and 14 C-serotonin, and attempts were made to determine whether heparin stimulated the platelet release reaction first with subsequent increased production of TxA2, or alternatively, whether heparin stimulated TxA2 production first with subsequent enhancement of the release reaction. In view of the demonstrated simultaneous release of 14 C-serotonin and 3 H-arachidonic acid metabolites, it appeared that either release of 14 C and 3 H occurs concurrently or, even if one of these events is dependent on the other, both events take place in rapid succession. Timed sequential studies revealed that in the presence of arachidonic acid, the addition of heparin hastened the apparently simultaneous release of both 14 C and 3 H

  11. The role of thromboxane A(2) in the pathogenesis of intrauterine growth restriction associated with maternal smoking in pregnancy.

    LENUS (Irish Health Repository)

    Lynch, Caoimhe M

    2012-02-01

    BACKGROUND: To examine the effect of maternal smoking in pregnancy on the production of two eicosanoids, thromboxane A(2) and prostacyclin I2, and their role in the pathogenesis of intrauterine growth restriction. METHODS: Prospective case control study enrolled smoking and non-smoking women at <\\/=14 weeks gestation. Maternal urine samples were obtained at <\\/=14, 28 and 36 weeks. High performance liquid chromatography tandem mass spectrometry (LC-MS-MS) was used to quantify 11-dehydrothromboxane B(2) (TX-M) and 2,3 dinor-6-ketoprostaglandin F1alpha (PG-M), stable urinary metabolites of thromboxane A(2) and prostacyclin I2. Confirmation of the smoking status was performed by quantitation of urinary nicotine metabolites. Data was analysed using SPSS and Stata((R)). RESULTS: Thirty five were enrolled in the smoking group and 32 in the non-smoking group. Smoking resulted higher levels of TX-M at <\\/=14, 28 and 36 weeks gestation. There was no difference in PG-M at any gestational time point between the two groups. The median customised birthweight centile in the smoking group was 17.0 (0-78) compared to 55.5 (4-100) in the non-smoking group (P<0.001). A causal relationship between elevated TX-M and IUGR could not be established. CONCLUSIONS: Maternal smoking in pregnancy is associated with altered eicosanoid production in favour of the vasoconstrictor thromboxane A(2) which occurs early in the first trimester.

  12. [Effect of losartan on human platelet activation by thromboxane A2].

    Science.gov (United States)

    Guerra, J I; Montón, M; Rodríguez-Feo, J A; Farré, J; Jiménez, A M; Núñez, A; Gómez, J; Rico, L; Marcos, P; Castilla, C; Sánchez De Miguel, L; Casado, S; López-Farré, A

    2000-04-01

    Previous studies have demonstrated that losartan, an AT-1 receptor antagonist of angiotensin II (Ang II) could block the receptor of thromboxane A2 (TXA2) in the vascular wall. The aim of the present study was to assess the effect of losartan on human platelet activation. Platelets were obtained from 15 healthy men between the age 26 and 40. Platelet activation was measured by changes in the light transmission of platelet-rich plasma stimulated by a synthetic TXA2 analogue, U46619 (5 x 10(-6) mol/l). The U46619-stimulated platelet aggregation was significantly inhibited by losartan in a dose-response manner. Only a high dose of EXP 3174 (5 10-5 mol/l), the in vivo active metabolite of losartan, was able to attenuate U46619-induced platelet activation. Captopril, an angiotensin I-converting inhibitor failed to modify U46619-induced platelet aggregation. Despite the platelets expressing AT-1 type receptors, of Ang II exogenous Ang II did not modify platelet aggregation induced by U46619. The binding of U46619 to platelets was competitively inhibited by losartan in dose-dependent manner. However, only a high dose of EXP 3174 reduced the binding of U46619. Captopril failed to modify the binding of U46619 to platelets. Losartan decreased platelet aggregation by a TXA2-dependent mechanism. EXP 3174 showed a lesser potency than losartan to reduce TXA2-platelet activation. Captopril and exogenous angiotensin II had no effect on human platelet activation. These results suggest that losartan reduced TXA2-dependent platelet activation independently of the blockade of AT-1 receptors.

  13. Thromboxane A(2 receptor stimulation promotes closure of the rat ductus arteriosus through enhancing neointima formation.

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    Tomohiro Yokota

    Full Text Available Ductus arteriosus (DA closure follows constriction and remodeling of the entire vessel wall. Patent ductus arteriosus occurs when the DA does not close after birth, and this condition is currently treated using cyclooxygenase inhibitors. However, the efficacy of cyclooxygenase inhibitors is often limited. Our previous study demonstrated that low-dose thromboxane A2 receptor (TP stimulation constricted the DA with minimal adverse effects in rat neonates. However, its effect on DA remodeling remains unknown. In this study, we focused on the impact of the exogenous TP stimulation on the DA remodeling, especially intimal thickening. Using DA explants from rat fetuses at embryonic day 19 as a ex vivo model and primary cultured rat DA smooth muscle cells from embryonic day 21 as a in vitro model, we evaluated the effect of TP stimulation on the DA remodeling. The selective TP agonists U46619 and I-BOP promoted neointima formation in the ex vivo DA explants, and TP stimulation increased DA SMC migration in a dose-dependent manner. Both effects were inhibited by the selective TP antagonist SQ29548 or the siRNA against TP. TP stimulation also increased DA SMC proliferation in the presence of 10% fetal bovine serum. LC/MS/MS analysis revealed that TP stimulation increased secretion of several extracellular matrix proteins that may contribute to an increase in neointima formation. In conclusion, we uncovered that exogenous administration of TP agonist promotes neointima formation through the induction of migration and proliferation of DA SMC, which could contribute to DA closure and also to its vasoconstrictive action.

  14. Mechanisms Involved in Thromboxane A2-induced Vasoconstriction of Rat Intracavernous Small Penile Arteries

    DEFF Research Database (Denmark)

    Grann, Martin; Comerma Steffensen, Simon Gabriel; Arcanjo, Daniel Dias Rufino

    2015-01-01

    relaxation in rat mesenteric arteries. Our findings suggest that U46619 contraction depends on Ca2+ influx through L-type and TRP channels, and ROCKdependent mechanisms in penile arteries. Inhibition of the ROCK pathway is a potential approach for the treatment of erectile dysfunction associated......Diabetes is associated with erectile dysfunction and with hypercontractility in erectile tissue and this is in part ascribed to increased formation of thromboxane. Rho kinase (ROCK) is a key regulator of calcium sensitization and contraction in vascular smooth muscle. This study investigated...... the role of calcium and ROCK in contraction evoked by activation of the thromboxane receptors. Rat intracavernous penile arteries were mounted for isometric tension and intracellular calcium ([Ca2+]i) recording and corpus cavernosum for measurements of MYPT1 phosphorylation. In penile arteries, U46619...

  15. Difluorothromboxane A2 and stereoisomers: Stable derivatives of thromboxane A2 with differential effects on platelets and blood vessels

    International Nuclear Information System (INIS)

    Morinelli, T.A.; Okwu, A.K.; Mais, D.E.; Halushka, P.V.; John, V.; Chen, Chienkuang; Fried, J.

    1989-01-01

    The present study reports on the selective effects on human platelets and canine saphenous veins of four stable difluorinated analogues and thromboxane A 2 (TXA 2 ), in which the characteristic 2,6-dioxa[3.1.1]bicycloheptane structure of TXA 2 has been retained. The four compounds differ in their stereochemistry of the 5,6 double bond and/or the 15-hydroxyl group. Only 10,10-difluoro-TXA 2 (compound I) with the natural stereochemistry of TXA 2 was an agonist in both platelets and canine saphenous veins. (15R)-10,10-Difluoro-TXA 2 (compound II), (5E)-10,10-difluoro-TXA 2 (compound III), and (5E,15R)-10,10-difluoro-TXA 2 (compound IV) were antagonists of platelet aggregation stimulated by compound I. However, compounds II, III, and IV stimulated contraction of canine saphenous veins. All four compounds could displace the TXA 2 /prostaglandin H 2 antagonist 9,11-dimethylmethano-11,12-methano-16-(3- 125 I-4-hydroxyphenyl)-13,14-dihydro-13-aza-15αβ-ω-tetranor-TXA 2 from its platelet receptor. These results support the existence of two subtypes of TXA 2 /prostaglandin H 2 receptors and emphasize the importance of the stereochemical requirements of these TXA 2 analogues for interaction with these receptors. These stable fluorinated TXA 2 analogues should prove useful tools for the further characterization of these and other TXA 2 /prostaglandin H 2 receptors

  16. Up-regulation of thromboxane A2 receptor expression by lipid soluble smoking particles through post-transcriptional mechanisms

    DEFF Research Database (Denmark)

    Zhang, Wei; Zhang, Yaping; Edvinsson, Lars

    2008-01-01

    Atherosclerosis is a key factor in vascular disease, and cigarette smoking is a well-known risk factor that may induce an inflammatory response and enhance plaque formation in arteries. Thromboxane (Tx) is one key inflammatory mediator involved in the pathogenesis of cardiovascular disease....... The present study was designed to test if lipid soluble smoking particles (DSP) enhance TxA(2) receptor (TP) expression in rat mesenteric arteries, and if intracellular mitogen-activated protein kinase (MAPK) pathways play a role. Organ culture of rat mesenteric arteries in the presence of DSP (0.2 microl...

  17. High-level expression, purification and characterization of a constitutively active thromboxane A2 receptor polymorphic variant.

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    Bing Xu

    Full Text Available G protein-coupled receptors (GPCRs exhibit some level of basal signaling even in the absence of a bound agonist. This basal or constitutive signaling can have important pathophysiological roles. In the past few years, a number of high resolution crystal structures of GPCRs have been reported, including two crystal structures of constitutively active mutants (CAM of the dim-light receptor, rhodopsin. The structural characterizations of CAMs are impeded by the lack of proper expression systems. The thromboxane A2 receptor (TP is a GPCR that mediates vasoconstriction and promotes thrombosis in response to the binding of thromboxane. Here, we report on the expression and purification of a genetic variant and CAM in TP, namely A160T, using tetracycline-inducible HEK293S-TetR and HEK293S (GnTI¯-TetR cell lines. Expression of the TP and the A160T genes in these mammalian cell lines resulted in a 4-fold increase in expression to a level of 15.8 ±0.3 pmol of receptor/mg of membrane protein. The receptors expressed in the HEK293S (GnTI(--TetR cell line showed homogeneous glycosylation. The functional yield of the receptors using a single step affinity purification was 45 µg/10⁶ cells. Temperature- dependent secondary structure changes of the purified TP and A160T receptors were characterized using circular dichroism (CD spectropolarimetry. The CD spectra shows that the loss of activity or thermal sensitivity that was previously observed for the A160T mutant, is not owing to large unfolding of the protein but rather to a more subtle effect. This is the first study to report on the successful high-level expression, purification, and biophysical characterization of a naturally occurring, diffusible ligand activated GPCR CAM.

  18. Roxicam pharmacological modulation of the prostacyclin-thromboxane system in heart failure-complicated acute myocardial infarction

    International Nuclear Information System (INIS)

    Shushlyapin, O.I.; Shelest, A.N.; Khossejn Shakhavat, A.F.M.

    1991-01-01

    The prostaglandin-thromboxane system, platelet hemostasis and central hemodynamics were evaluated in 51 patients with heart failure-complicated acute myocardial infarction. The concentration of active metabolites of thromboxane-prostacyclin system was determined by means of radioimmunoassay. The new non-steroidal antiinflammatory agent roxicam was shown to selectively inhibit thromboxane, without affecting prostacyclin levels. The agent may be use in therapy in patients with myocardial infarction concurrent with heart failure

  19. Ozagrel hydrochloride, a selective thromboxane A2 synthase inhibitor, alleviates liver injury induced by acetaminophen overdose in mice

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    Tomishima Yoshiro

    2013-01-01

    Full Text Available Abstract Background Overdosed acetaminophen (paracetamol, N-acetyl-p-aminophenol; APAP causes severe liver injury. We examined the effects of ozagrel, a selective thromboxane A2 (TXA2 synthase inhibitor, on liver injury induced by APAP overdose in mice. Methods Hepatotoxicity was induced to ICR male mice by an intraperitoneal injection with APAP (330 mg/kg. The effects of ozagrel (200 mg/kg treatment 30 min after the APAP injection were evaluated with mortality, serum alanine aminotransferase (ALT levels and hepatic changes, including histopathology, DNA fragmentation, mRNA expression and total glutathione contents. The impact of ozagrel (0.001-1 mg/mL on cytochrome P450 2E1 (CYP2E1 activity in mouse hepatic microsome was examined. RLC-16 cells, a rat hepatocytes cell line, were exposed to 0.25 mM N-acetyl-p-benzoquinone imine (NAPQI, a hepatotoxic metabolite of APAP. In this model, the cytoprotective effects of ozagrel (1–100 muM were evaluated by the WST-1 cell viability assay. Results Ozagel treatment significantly attenuated higher mortality, elevated serum alanine aminotransferase levels, excessive hepatic centrilobular necrosis, hemorrhaging and DNA fragmentation, as well as increase in plasma 2,3-dinor thromboxane B2 levels induced by APAP injection. Ozagrel also inhibited the hepatic expression of cell death-related mRNAs induced by APAP, such as jun oncogene, FBJ osteosarcoma oncogene (fos and C/EBP homologous protein (chop, but did not suppress B-cell lymphoma 2-like protein11 (bim expression and hepatic total glutathione depletion. These results show ozagrel can inhibit not all hepatic changes but can reduce the hepatic necrosis. Ozagrel had little impact on CYP2E1 activity involving the NAPQI production. In addition, ozagrel significantly attenuated cell injury induced by NAPQI in RLC-16. Conclusions We demonstrate that the TXA2 synthase inhibitor, ozagrel, dramatically alleviates liver injury induced by APAP in mice, and suggest

  20. A novel thromboxane A2 receptor N42S variant results in reduced surface expression and platelet dysfunction.

    Science.gov (United States)

    Nisar, Shaista P; Lordkipanidzé, Marie; Jones, Matthew L; Dawood, Ban; Murden, Sherina; Cunningham, Margaret R; Mumford, Andrew D; Wilde, Jonathan T; Watson, Steve P; Mundell, Stuart J; Lowe, Gillian C

    2014-05-05

    A small number of thromboxane receptor variants have been described in patients with a bleeding history that result in platelet dysfunction. We have identified a patient with a history of significant bleeding, who expresses a novel heterozygous thromboxane receptor variant that predicts an asparagine to serine substitution (N42S). This asparagine is conserved across all class A GPCRs, suggesting a vital role for receptor structure and function.We investigated the functional consequences of the TP receptor heterozygous N42S substitution by performing platelet function studies on platelet-rich plasma taken from the patient and healthy controls. We investigated the N42S mutation by expressing the wild-type (WT) and mutant receptor in human embryonic kidney (HEK) cells. Aggregation studies showed an ablation of arachidonic acid responses in the patient, whilst there was right-ward shift of the U46619 concentration response curve (CRC). Thromboxane generation was unaffected. Calcium mobilisation studies in cells lines showed a rightward shift of the U46619 CRC in N42S-expressing cells compared to WT. Radioligand binding studies revealed a reduction in BMax in platelets taken from the patient and in N42S-expressing cells, whilst cell studies confirmed poor surface expression. We have identified a novel thromboxane receptor variant, N42S, which results in platelet dysfunction due to reduced surface expression. It is associated with a significant bleeding history in the patient in whom it was identified. This is the first description of a naturally occurring variant that results in the substitution of this highly conserved residue and confirms the importance of this residue for correct GPCR function.

  1. Kupffer cell depletion attenuates leptin-mediated methoxamine-stimulated portal perfusion pressure and thromboxane A2 release in a rodent model of NASH-cirrhosis.

    Science.gov (United States)

    Yang, Ying-Ying; Huang, Yi-Tsau; Tsai, Tung-Hu; Hou, Ming-Chih; Lee, Fa-Yauh; Lee, Shou-Dong; Lin, Han-Chieh

    2012-12-01

    Cirrhotic portal hypertension is characterized by increased hepatic oxidative stress, AA (arachidonic acid)-derived TXA(2) (thromboxane A(2)) release and exaggerated hepatic response to the α-adrenergic agonist MTX (methoxamine). Besides promoting hepatic fibrosis, the role of hyperleptinaemia in the modulation of vascular response in NASH (non-alcoholic steatohepatitis) rat livers remains unknown. The aim of the present study was to explore the possible links between hyperleptinaemia and the disarrangement in the hepatic microcirculation. NASH-cirrhosis with hyperleptinaemia was induced in lean rats by feeding with an HF/MCD (high-fat/methionine-choline-deficient) diet. Portal haemodynamics, various substances, protein and mRNA expression and PUFA (polyunsaturated fatty acid) composition were measured. Finally, the effects of leptin pre-infusion on TXA(2) release and concentration-PPP (portal perfusion pressure) curves in response to MTX were evaluated by simultaneously pre-treatment with the Kupffer cell inactivators GdCl(3) (gadolinium chloride) or EC (encapsulated clodronate), the TXS (TXA(2) synthase) inhibitor furegrelate, the TP receptor (TXA(2) receptor) antagonist SQ29548 and the dual TXS/TP receptor antagonist BM567. In HF/MCD+leptin-lean rats, cirrhosis-induced PPP and MTX hyper-responsiveness were associated with increased hepatic TXA(2) production, TBARS (thiobarbituric acid-reacting substances) levels and the AA (arachidonic acid)/n-3 PUFA ratio, and up-regulation of hepatic leptin, FAS (fatty acid synthase), NADPH oxidase subunits, TXS, TP receptor, TGFβ(1) (transforming growth factor β(1)) proteins and mRNAs. Pre-infusion of leptin significantly enhanced MTX-stimulated PPP elevation and TXA(2) release, which were attenuated by GdCl(3) and EC pre-treatment. Concomitantly pre-incubation with BM567, but not furegrelate or SQ29548, significantly abolished the leptin-enhanced MTX-stimulated increase in PPP in NASH-cirrhotic rats. Hyperleptinaemia

  2. Regulation of protein kinase C-related kinase (PRK) signalling by the TPα and TPβ isoforms of the human thromboxane A2 receptor: Implications for thromboxane- and androgen- dependent neoplastic and epigenetic responses in prostate cancer.

    Science.gov (United States)

    O'Sullivan, Aine G; Mulvaney, Eamon P; Kinsella, B Therese

    2017-04-01

    The prostanoid thromboxane (TX) A 2 and its T Prostanoid receptor (the TP) are increasingly implicated in prostate cancer (PCa). Mechanistically, we recently discovered that both TPα and TPβ form functional signalling complexes with members of the protein kinase C-related kinase (PRK) family, AGC- kinases essential for the epigenetic regulation of androgen receptor (AR)-dependent transcription and promising therapeutic targets for treatment of castrate-resistant prostate cancer (CRPC). Critically, similar to androgens, activation of the PRKs through the TXA 2 /TP signalling axis induces phosphorylation of histone H3 at Thr11 (H3Thr11), a marker of androgen-induced chromatin remodelling and transcriptional activation, raising the possibility that TXA 2 -TP signalling can mimic and/or enhance AR-induced cellular changes even in the absence of circulating androgens such as in CRPC. Hence the aim of the current study was to investigate whether TXA 2 /TP-induced PRK activation can mimic and/or enhance AR-mediated cellular responses in the model androgen-responsive prostate adenocarcinoma LNCaP cell line. We reveal that TXA 2 /TP signalling can act as a neoplastic- and epigenetic-regulator, promoting and enhancing both AR-associated chromatin remodelling (H3Thr11 phosphorylation, WDR5 recruitment and acetylation of histone H4 at lysine 16) and AR-mediated transcriptional activation (e.g of the KLK3/prostate-specific antigen and TMPRSS2 genes) through mechanisms involving TPα/TPβ mediated-PRK1 and PRK2, but not PRK3, signalling complexes. Overall, these data demonstrate that TPα/TPβ can act as neoplastic and epigenetic regulators by mimicking and/or enhancing the actions of androgens within the prostate and provides further mechanistic insights into the role of the TXA 2 /TP signalling axis in PCa, including potentially in CRPC. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Differential effects of phorbol 12-myristate 13-acetate and diacylglycerols on thromboxane A2-independent phospholipase A2 activation in collage-stimulated human platelets.

    Science.gov (United States)

    Reddy, S; Rao, G H; Murthy, M

    1994-04-01

    We investigated the priming effects of protein kinase C (PKC) activators such as phorbol 12-myristate 13-acetate (PMA), 1,2-DiC8 and OAG, and 1,3-DiC8 (a poor activator of PKC) on thromboxane A2 (TxA2)-independent phospholipase A2 (PLA2) activation in human platelets using collagen and A23187 as agonists. We measured PLA2 activation in collagen-stimulated platelets in the presence of BW755C, which abolished TxA2 synthesis, rise in cytosolic Ca2+, and aggregation. In the presence of PMA (50 nM), the amount of arachidonic acid (AA) released in platelets stimulated with collagen and A23187 represented 300% (13.85 nmol versus 4.5 nmol) and 400% (28 nmol versus 7 nmol) of controls (without PMA), respectively, while 1,2-DiC8, OAG, and 1,3-DiC8 increased TxA2-independent AA release by 50% in A23187-stimulated platelets and had no effect on the release of AA in collagen-stimulated platelets. Interestingly, 1,3-DiC8, which is a poor activator of PKC, was as effective as the other two DAGs (OAG and 1,2-DiC8) in priming TxA2-independent PLA2 activation, but was less effective than PMA in platelets stimulated with A23187. These results suggest that the TXA2-dependent IP3-mediated rise in cytosolic Ca2+ may not be obligatory for priming PLA2 activation in the presence of PMA in collagen-stimulated platelets. In contrast, 1,2-DiC8, OAG, and 1,3-DiC8 likely enhanced PLA2 activation via intracellular Ca2+ as they selectively affect this enzyme only in A23187-stimulated platelets. We also observed a significant increase in both saturated (palmitic and stearic acids) and unsaturated fatty acids (oleic and linoleic acids) in platelets stimulated by collagen or A23187 in the presence of PMA (50 nM), but not in the presence of DAGs. These findings imply that PMA may also affect the activation of DAG/MAG lipases, PLA1, or nonspecific PLA2. Since both 1,2-DiC8 and OAG exert no significant effect on the release of these fatty acids, the effects observed with PMA on DAG lipase/PLA1 may not

  4. A novel thromboxane A2 receptor D304N variant that abrogates ligand binding in a patient with a bleeding diathesis.

    Science.gov (United States)

    Mumford, Andrew D; Dawood, Ban B; Daly, Martina E; Murden, Sherina L; Williams, Michael D; Protty, Majd B; Spalton, Jennifer C; Wheatley, Mark; Mundell, Stuart J; Watson, Steve P

    2010-01-14

    We investigated the cause of mild mucocutaneous bleeding in a 14-year-old male patient (P1). Platelet aggregation and ATP secretion induced by arachidonic acid and the thromboxane A(2) receptor (TxA(2)R) agonist U46619 were reduced in P1 compared with controls, whereas the responses to other platelet agonists were retained. P1 was heterozygous for a transversion within the TBXA2R gene predictive of a D304N substitution in the TxA(2)R. In Chinese hamster ovary-K1 cells expressing the variant D304N TxA(2)R, U46619 did not increase cytosolic free Ca(2+) concentration, indicating loss of receptor function. The TxA(2)R antagonist [(3)H]-SQ29548 showed an approximate 50% decrease in binding to platelets from P1 but absent binding to Chinese hamster ovary-K1 cells expressing variant D304N TxA(2)R. This is the second naturally occurring TxA(2)R variant to be associated with platelet dysfunction and the first in which loss of receptor function is associated with reduced ligand binding. D304 lies within a conserved NPXXY motif in transmembrane domain 7 of the TxA(2)R that is a key structural element in family A G protein-coupled receptors. Our demonstration that the D304N substitution causes clinically significant platelet dysfunction by reducing ligand binding establishes the importance of the NPXXY motif for TxA(2)R function in vivo.

  5. Reciprocal regulation of platelet responses to P2Y and thromboxane receptor activation.

    Science.gov (United States)

    Barton, J F; Hardy, A R; Poole, A W; Mundell, S J

    2008-03-01

    Thromboxane A(2) and ADP are two major platelet agonists that stimulate two sets of G protein-coupled receptors to activate platelets. Although aggregation responses to ADP and thromboxane desensitize, there are no reports currently addressing whether activation by one agonist may heterologously desensitize responses to the other. To demonstrate whether responses to ADP or U46619 may be modulated by prior treatment of platelets with the alternate agonist, revealing a level of cross-desensitization between receptor systems. Here we show that pretreatment of platelets with either agonist substantially desensitizes aggregation responses to the other agonist. Calcium responses to thromboxane receptor activation are desensitized by preactivation of P2Y(1) but not P2Y(12) receptors. This heterologous desensitization is mediated by a protein kinase C (PKC)-independent mechanism. Reciprocally, calcium responses to ADP are desensitized by pretreatment of platelets with the thromboxane analogue, U46619, and P2Y(12)-mediated inhibition of adenylate cyclase is also desensitized by pretreatment with U46619. In this direction, desensitization is comprised of two components, a true heterologous component that is PKC-independent, and a homologous component that is mediated through stimulated release of dense granule ADP. This study reveals cross-desensitization between ADP and thromboxane receptor signaling in human platelets. Cross-desensitization is mediated by protein kinases, involving PKC-dependent and independent pathways, and indicates that alterations in the activation state of one receptor may have effects upon the sensitivity of the other receptor system.

  6. Thromboxane production in morbidly obese subjects.

    Science.gov (United States)

    Graziani, Francesca; Biasucci, Luigi M; Cialdella, Pio; Liuzzo, Giovanna; Giubilato, Simona; Della Bona, Roberta; Pulcinelli, Fabio M; Iaconelli, Amerigo; Mingrone, Geltrude; Crea, Filippo

    2011-06-01

    Postmortem studies have demonstrated that morbidly obese subjects, surprisingly, have less coronary atherosclerosis than obese subjects. However, the reasons for this apparent protection from atherosclerosis are not yet clear. Thromboxane A2, a marker of platelet activation, is greater in obese subjects than in lean subjects, and this might be a clue to their increased cardiovascular risk. However, data on thromboxane A2 in morbidly obese subjects are lacking; therefore, we hypothesized that lower levels of thromboxane A2 in morbidly obese subjects might play a role in their lower atherothrombotic burden. We measured the serum levels of thromboxane B2 (TxB2), a stable metabolite of thromboxane A2, high-sensitivity C-reactive protein (hs-CRP) and leptin in 17 lean subjects (body mass index [BMI] 22.9 ± 1.6 kg/m(2)), 25 obese subjects (BMI 32.6 ± 2.4 kg/m(2)), and 23 morbidly obese subjects (BMI 48.6 ± 7.1 kg/m(2)), without insulin resistance, diabetes, or overt cardiovascular disease. The serum TxB2 levels were lower in the lean subjects than in the obese subjects (p = 0.046) and in the morbidly obese subjects than in the lean and obese subjects (p = 0.015 and p lean subjects (hs-CRP, p lean subjects (p lean subjects, suggesting that reduced platelet activation could play a role in the paradoxical protection of morbidly obese subjects from atherosclerosis, despite the greater levels of leptin. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Lack of protective effect of thromboxane synthetase inhibitor (CGS-13080) on single dose radiated canine intestine

    International Nuclear Information System (INIS)

    Barter, J.F.; Marlow, D.; Kamath, R.K.; Harbert, J.; Torrisi, J.R.; Barnes, W.A.; Potkul, R.K.; Newsome, J.T.; Delgado, G.

    1991-01-01

    The effect of a thromboxane A2 synthetase inhibitor (CGS-13080) on canine intestine was studied using a single dose of radiation, and radioactive microspheres were used to determine resultant blood flow. Thromboxane A2 causes vasospasm and platelet aggregation and may play a dominant role in radiation injury. However, there was no effect on the intestinal blood flow diminution occurring after radiation in this laboratory model using this thromboxane A2 synthetase inhibitor

  8. Piperine Inhibits the Activities of Platelet Cytosolic Phospholipase A2 and Thromboxane A2 Synthase without Affecting Cyclooxygenase-1 Activity: Different Mechanisms of Action Are Involved in the Inhibition of Platelet Aggregation and Macrophage Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Dong Ju Son

    2014-08-01

    Full Text Available PURPOSE: Piperine, a major alkaloid of black pepper (Piper nigrum and long pepper (Piper longum, was shown to have anti-inflammatory activity through the suppression of cyclooxygenase (COX-2 gene expression and enzyme activity. It is also reported to exhibit anti-platelet activity, but the mechanism underlying this action remains unknown. In this study, we investigated a putative anti-platelet aggregation mechanism involving arachidonic acid (AA metabolism and how this compares with the mechanism by which it inhibits macrophage inflammatory responses; METHODS: Rabbit platelets and murine macrophage RAW264.7 cells were treated with piperine, and the effect of piperine on the activity of AA-metabolizing enzymes, including cytosolic phospholipase A2 (cPLA2, COX-1, COX-2, and thromboxane A2 (TXA2 synthase, as well as its effect on AA liberation from the plasma membrane components, were assessed using isotopic labeling methods and enzyme immunoassay kit; RESULTS: Piperine significantly suppressed AA liberation by attenuating cPLA2 activity in collagen-stimulated platelets. It also significantly inhibited the activity of TXA2 synthase, but not of COX-1, in platelets. These results suggest that piperine inhibits platelet aggregation by attenuating cPLA2 and TXA2 synthase activities, rather than through the inhibition of COX-1 activity. On the other hand, piperine significantly inhibited lipopolysaccharide-induced generation of prostaglandin (PGE2 and PGD2 in RAW264.7 cells by suppressing the activity of COX-2, without effect on cPLA2; CONCLUSION: Our findings indicate that piperine inhibits platelet aggregation and macrophage inflammatory response by different mechanisms.

  9. Reduced methylation of the thromboxane synthase gene is correlated with its increased vascular expression in preeclampsia.

    Science.gov (United States)

    Mousa, Ahmad A; Strauss, Jerome F; Walsh, Scott W

    2012-06-01

    Preeclampsia is characterized by increased thromboxane and decreased prostacyclin levels, which predate symptoms, and can explain some of the clinical manifestations of preeclampsia, including hypertension and thrombosis. In this study, we examined DNA methylation of the promoter region of the thromboxane synthase gene (TBXAS1) and the expression of thromboxane synthase in systemic blood vessels of normal pregnant and preeclamptic women. Thromboxane synthase is responsible for the synthesis of thromboxane A(2), a potent vasoconstrictor and activator of platelets. We also examined the effect of experimentally induced DNA hypomethylation on the expression of thromboxane synthase in a neutrophil-like cell line (HL-60 cells) and in cultured vascular smooth muscle and endothelial cells. We found that DNA methylation of the TBXAS1 promoter was decreased and thromboxane synthase expression was increased in omental arteries of preeclamptic women as compared with normal pregnant women. Increased thromboxane synthase expression was observed in vascular smooth muscles cells, endothelial cells, and infiltrating neutrophils. Experimentally induced DNA hypomethylation only increased expression of thromboxane synthase in the neutrophil-like cell line, whereas tumor necrosis factor-α, a neutrophil product, increased its expression in cultured vascular smooth muscle cells. Our study suggests that epigenetic mechanisms and release of tumor necrosis factor-α by infiltrating neutrophils could contribute to the increased expression of thromboxane synthase in maternal systemic blood vessels, contributing to the hypertension and coagulation abnormalities associated with preeclampsia.

  10. Antiplatelet effect of phloroglucinol is related to inhibition of cyclooxygenase, reactive oxygen species, ERK/p38 signaling and thromboxane A2 production

    International Nuclear Information System (INIS)

    Chang, Mei-Chi; Chang, Hsiao-Hua; Chan, Chiu-Po; Chou, Han-Yi; Chang, Bei-En; Yeung, Sin-Yuet; Wang, Tong-Mei; Jeng, Jiiang-Huei

    2012-01-01

    Platelet dysfunction is a major risk factor of cardiovascular diseases such as atherosclerosis, stroke and myocardial infarction. Many antiplatelet agents are used for prevention and treatment of these diseases. In this study, phloroglucinol (2.5–25 μM) suppressed AA-induced platelet aggregation and thromboxane B 2 (TXB 2 ) production, but not U46619-induced platelet aggregation. Phloroglucinol (100–250 μM) showed little cytotoxicity to platelets. Phloroglucinol inhibited the COX-1 and COX-2 activities by 45–74% and 49–72% respectively at concentrations of 10–50 μM. At concentrations of 1 and 5 μM, phloroglucinol attenuated the AA-induced ROS production in platelets by 30% and 53%, with an IC 50 of 13.8 μM. Phloroglucinol also inhibited the PMA-stimulated ROS production in PMN. Preincubation of platelets by phloroglucinol (10–25 μM) markedly attenuated the AA-induced ERK and p38 phosphorylation. Intravenous administration of phloroglucinol (2.5 and 5 μmol/mouse) suppressed the ex vivo AA-induced platelet aggregation by 57–71%. Phloroglucinol administration also elevated the mice tail bleeding time. Moreover, phloroglucinol inhibited the IL-1β-induced PGE 2 production in pulp fibroblasts. These results indicate that antiplatelet and anti-inflammatory effects of phloroglucinol are related to inhibition of COX, ROS and TXA2 production as well as ERK/p38 phosphorylation in platelets. Phloroglucinol further suppress PMA-induced ROS production in PMN. The antiplatelet effect of phloroglucinol was confirmed by ex vivo study. Clinically, the consumption of phloroglucinol-containing food/natural products as nutritional supplement may be helpful to cardiovascular health. Phloroglucinol has potential pharmacological use. -- Highlights: ► Phloroglucinol suppressed AA-induced platelet aggregation and thromboxane production. ► Phloroglucinol inhibited COX activity and IL-1b-induced PGE2 production in fibroblast. ► Phloroglucinol declined platelet and

  11. Thromboxane synthesis inhibitors and postprandial jejunal capillary exchange capacity.

    Science.gov (United States)

    Mangino, M J; Chou, C C

    1988-05-01

    The effects of thromboxane synthesis inhibitors (imidazole and U 63557A; Upjohn) and the cyclooxygenase inhibitor, mefenamic acid, on jejunal capillary filtration coefficients (Kfc) were determined in dogs before and during the presence of predigested food in the jejunal lumen. The jejunal Kfc increased significantly soon after the placement of a predigested test food containing all major constituents of diet. The Kfc remained elevated as long as the food was present in the lumen (15 min). Mefenamic acid (10 mg/kg iv) did not significantly alter resting jejunal Kfc or alter the food-induced increase in Kfc. Imidazole (5.0 mg/min ia) or U 63557A (5.0 mg/kg iv) per se significantly increased jejunal Kfc. Placement of digested food further increased the Kfc to levels significantly higher than those observed before administration of the two thromboxane synthase inhibitors. Production of thromboxane B2 by jejunal tissue was significantly reduced and 6-ketoprostaglandin F1 alpha (the stable hydrolysis product of prostacyclin) production was significantly increased after administration of U 63557A. Our study indicates that the relative production of endogenous thromboxanes and other prostanoids modulates jejunal capillary exchange capacity in the absence or presence of digested food in the jejunal lumen.

  12. Clinical significance of determination of plasma endothelin (ET), thromboxane A2(TXA2) and prostacyclin (PGI2) contents in neonates with hypoxic-ischemic encephalopathy

    International Nuclear Information System (INIS)

    Liu Hui; Chen Jing; Wang Haifeng; Zhu Hongyan

    2008-01-01

    Objective: To explore the role of plasma ET, TXA 2 , PGI 2 in the intensification of neonates hypoxic-ischemic encephalopathy. Methods: The concentrations of plasma ET, TXB 2 , 6-keto-PGF 1α were detected with radioimmunoassay in 33 neonates with hypoxic-ischemic encephalopathy and 30 controls. Results: The plasma ET, TXB 2 levels in neonates with hypoxic-ischemic encephalopathy were significantly higher than those in controls (P 1α levels were significantly lower (P 2 but negatively correlated with those of 6-keto-PGF 1α (both P 2 with disturbance of the normal feedback modulation mechanism might play an important role in the pathogenesis of neonates hypoxic-ischemic encephalopathy. (authors)

  13. Time-dependent effect of orchidectomy on vascular nitric oxide and thromboxane A2 release. Functional implications to control cell proliferation through activation of the epidermal growth factor receptor.

    Directory of Open Access Journals (Sweden)

    Marta del Campo

    Full Text Available This study analyzes whether the release of nitric oxide (NO and thromboxane A2 (TXA2 depends on the time lapsed since gonadal function is lost, and their correlation with the proliferation of vascular smooth muscle cells (VSMC mediated by the epidermal growth factor receptor (EGFR. For this purpose, aortic and mesenteric artery segments from control and 6-weeks or 5-months orchidectomized rats were used to measure NO and TXA2 release. The results showed that the basal and acetylcholine (ACh-induced NO release were decreased 6 weeks post-orchidectomy both in aorta and mesenteric artery, but were recovered 5 months thereafter up to levels similar to those found in arteries from control rats. The basal and ACh-induced TXA2 release increased in aorta and mesenteric artery 6 weeks post-orchidectomy, and was maintained at high levels 5 months thereafter. Since we previously observed that orchidectomy, which decreased testosterone level, enlarged the muscular layer of mesenteric arteries, the effect of testosterone on VSMC proliferation was analyzed. The results showed that treatment of cultured VSMC with testosterone downregulated mitogenic signaling pathways initiated by the ligand-dependent activation of the EGFR. In contrast, the EGFR pathways were constitutively active in mesenteric arteries of long-term orchidectomized rats. Thus, the exposure of mesenteric arteries from control rats to epidermal growth factor (EGF induced the activation of EGFR signaling pathways. However, the addition of EGF to arteries from orchidectomized rats failed to induce a further activation of these pathways. In conclusion, this study shows that the release of NO depends on the time lapsed since the gonadal function is lost, while the release of TXA2 is already increased after short periods post-orchidectomy. The alterations in these signaling molecules could contribute to the constitutive activation of the EGFR and its downstream signaling pathways after long period

  14. Urinary Thromboxane B2 and Thromboxane Receptors in Bladder Cancer: Opportunity for Detection and Monitoring

    OpenAIRE

    Moussa, Omar; Ciupek, Andrew; Watson, Dennis K.; Halushka, Perry V.

    2011-01-01

    We have previously found increased expression of thromboxane synthase (TXAS) and thromboxane receptor (TP) beta isoform in the tissues of patients with bladder cancer. Studies in cell lines and mice have indicated a potential significant role of the thromboxane signaling pathway in the pathogenesis of human bladder cancer. This study was designed to determine if the changes observed in the tissues of patients with bladder cancer were mirrored by changes in the urine of these patients. We foun...

  15. Radioimmunological determination of thromboxane release in cardiac anaphylaxis

    Energy Technology Data Exchange (ETDEWEB)

    Anhut, H; Bernauer, W; Peskar, B A [Freiburg Univ. (Germany, F.R.). Dept. of Pharmacology

    1977-07-01

    A sensitive and specific radioimmunoassay for thromboxane B/sub 2/ was developed. Using the radioimmunoassay, substantial amounts of thromboxane B/sub 2/ were detected in perfusates of anaphylactic guinea pig hearts. Indomethacin decreased thromboxane B/sub 2/ levels in the perfusates to below the detection limit of the radioimmunoassay and concomitantly delayed the onset of coronary vasoconstriction after antigenic challenge.

  16. Effects of the dual TP receptor antagonist and thromboxane synthase inhibitor EV-077 on human endothelial and vascular smooth muscle cells

    International Nuclear Information System (INIS)

    Petri, Marcelo H.; Tellier, Céline; Michiels, Carine; Ellertsen, Ingvill; Dogné, Jean-Michel; Bäck, Magnus

    2013-01-01

    Highlights: •EV-077 reduced TNF-α induced inflammation in endothelial cells. •The thromboxane mimetic U69915 enhanced vascular smooth muscle cell proliferation. •EV-077 inhibited smooth muscle cell proliferation. -- Abstract: The prothrombotic mediator thromboxane A 2 is derived from arachidonic acid metabolism through the cyclooxygenase and thromboxane synthase pathways, and transduces its effect through the thromboxane prostanoid (TP) receptor. The aim of this study was to determine the effect of the TP receptor antagonist and thromboxane synthase inhibitor EV-077 on inflammatory markers in human umbilical vein endothelial cells and on human coronary artery smooth muscle cell proliferation. To this end, mRNA levels of different proinflammatory mediators were studied by real time quantitative PCR, supernatants were analyzed by enzyme immune assay, and cell proliferation was assessed using WST-1. EV-077 significantly decreased mRNA levels of ICAM-1 and PTX3 after TNFα incubation, whereas concentrations of 6-keto PGF1α in supernatants of endothelial cells incubated with TNFα were significantly increased after EV-077 treatment. Although U46619 did not alter coronary artery smooth muscle cell proliferation, this thromboxane mimetic enhanced the proliferation induced by serum, insulin and growth factors, which was significantly inhibited by EV-077. In conclusion, EV-077 inhibited TNFα-induced endothelial inflammation and reduced the enhancement of smooth muscle cell proliferation induced by a thromboxane mimetic, supporting that the thromboxane pathway may be associated with early atherosclerosis in terms of endothelial dysfunction and vascular hypertrophy

  17. Quercetin modulates activities of Taiwan cobra phospholipase A 2 ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Biosciences; Volume 37; Issue 2. Quercetin modulates activities of Taiwan cobra phospholipase A2 via its effects on membrane structure and membrane-bound mode of phospholipase A2. Yi-Ling Chiou Shinne-Ren Lin Wan-Ping Hu Long-Sen Chang. Articles Volume 37 Issue 2 June 2012 pp ...

  18. Anti-thromboxane B2 antibodies protect against acetaminophen-induced liver injury in mice

    Directory of Open Access Journals (Sweden)

    Ivan Ćavar

    2011-12-01

    Full Text Available Prostanoids are lipid compounds that mediate a variety of physiological and pathological functions in almost all body tissues and organs. Thromboxane (TX A2 is a powerful inducer of platelet aggregation and vasoconstriction and it has ulcerogenic activity in the gastrointestinal tract. Overdose or chronic use of a high dose of acetaminophen (N-acetyl-paminophenol, APAP is a major cause of acute liver failure in the Western world. We investigated whether TXA2 plays a role in host response to toxic effect of APAP. CBA/H Zg mice of both sexes were intoxicated with a single lethal or high sublethal dose of APAP, which was administered to animals by oral gavage. The toxicity of APAP was determined by observing the survival of mice during 48 h, by measuring concentration of alanine-aminotransferase (ALT in plasma 20-22 h after APAP administration and by liver histology. The results have shown that anti-thromboxane (TX B2 antibodies (anti-TXB2 and a selective inhibitor of thromboxane (TX synthase, benzylimidazole (BZI, were significantly hepatoprotective, while a selective thromboxane receptor (TPR antagonist, daltroban, was slightly protective in this model of acute liver injury. A stabile metabolite of TXA2, TXB2, and a stabile agonist of TPR, U-46619, had no influence on APAP-induced liver damage. Our findings suggest that TXA2 has a pathogenic role in acute liver toxicity induced with APAP, which was highly abrogated by administration of anti-TXB2. According to our results, this protection is mediated, at least in part, through decreased production of TXB2 by liver fragments ex vivo.

  19. Characterization of the human gene (TBXAS1) encoding thromboxane synthase.

    Science.gov (United States)

    Miyata, A; Yokoyama, C; Ihara, H; Bandoh, S; Takeda, O; Takahashi, E; Tanabe, T

    1994-09-01

    The gene encoding human thromboxane synthase (TBXAS1) was isolated from a human EMBL3 genomic library using human platelet thromboxane synthase cDNA as a probe. Nucleotide sequencing revealed that the human thromboxane synthase gene spans more than 75 kb and consists of 13 exons and 12 introns, of which the splice donor and acceptor sites conform to the GT/AG rule. The exon-intron boundaries of the thromboxane synthase gene were similar to those of the human cytochrome P450 nifedipine oxidase gene (CYP3A4) except for introns 9 and 10, although the primary sequences of these enzymes exhibited 35.8% identity each other. The 1.2-kb of the 5'-flanking region sequence contained potential binding sites for several transcription factors (AP-1, AP-2, GATA-1, CCAAT box, xenobiotic-response element, PEA-3, LF-A1, myb, basic transcription element and cAMP-response element). Primer-extension analysis indicated the multiple transcription-start sites, and the major start site was identified as an adenine residue located 142 bases upstream of the translation-initiation site. However, neither a typical TATA box nor a typical CAAT box is found within the 100-b upstream of the translation-initiation site. Southern-blot analysis revealed the presence of one copy of the thromboxane synthase gene per haploid genome. Furthermore, a fluorescence in situ hybridization study revealed that the human gene for thromboxane synthase is localized to band q33-q34 of the long arm of chromosome 7. A tissue-distribution study demonstrated that thromboxane synthase mRNA is widely expressed in human tissues and is particularly abundant in peripheral blood leukocyte, spleen, lung and liver. The low but significant levels of mRNA were observed in kidney, placenta and thymus.

  20. Inhibitory Effect of the Punica granatum Fruit Extract on Angiotensin-II Type I Receptor and Thromboxane B2 in Endothelial Cells Induced by Plasma from Preeclamptic Patients.

    Science.gov (United States)

    Kusumawati, Widya; Keman, Kusnarman; Soeharto, Setyawati

    2016-01-01

    This study aims to evaluate whether the Punica granatum fruit extract modulates the Angiotensin-II Type I receptor (AT1-R) and thromboxane B2 level in endothelial cells induced by plasma from preeclamptic patients. Endothelial cells were obtained from human umbilical vascular endothelial cells. At confluence, endothelial cells were divided into five groups, which included endothelial cells exposed to 2% plasma from normal pregnancy (NP), endothelial cells exposed to 2% plasma from preeclamptic patients (PP), and endothelial cells exposed to PP in the presence of ethanolic extract of Punica granatum (PP + PG) at the following three doses: 14; 28; and 56 ppm. The expression of AT1-R was observed by immunohistochemistry technique, and thromboxane B2 level was done by immunoassay technique. Plasma from PP significantly increased AT1-R expression and thromboxane B2 levels compared to cells treated by normal pregnancy plasma. The increasing of AT1-R expression significantly (P Punica granatum extract. Moreover, the increasing of thromboxane B2 levels significantly (P Punica granatum extract. We further concluded that Punica granatum fruit protects and inhibits the sensitivity of endothelial cells to plasma from preeclamptic patients due to inhibition of AT1-R expression (56 ppm) and reduced thromboxane B2 levels (14 ppm).

  1. Prostanoids modulate inflammation and alloimmune responses during graft rejection

    Directory of Open Access Journals (Sweden)

    P.N. Rocha

    2005-12-01

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

  2. Thromboxane plays a role in postprandial jejunal oxygen uptake and capillary exchange.

    Science.gov (United States)

    Alemayehu, A; Chou, C C

    1990-09-01

    The effects of a thromboxane A2 (TxA2)-endoperoxide receptor antagonist, SQ 29548, on jejunal blood flow, oxygen uptake, and capillary filtration coefficient (Kfc) were determined in anesthetized dogs under resting conditions and during the presence of predigested food in the jejunal lumen in three series of experiments. In series 1, 2.0 micrograms intra-arterial administration of SQ 29548 was found to abolish completely the vasoconstrictor action of graded doses (0.05-2.0 micrograms) of intra-arterial injection of a TxA2-endoperoxide analogue, U44069. SQ 29548 (2.0 micrograms ia) per se did not significantly alter resting jejunal blood flow, oxygen uptake, capillary pressure, or Kfc. Before SQ 29548, placement of food plus bile into the jejunal lumen increased blood flow +42 +/- 9%, oxygen uptake +28 +/- 7%, and Kfc +24 +/- 6%. After SQ 29548, the food placement increased blood flow +37 +/- 8%, oxygen uptake +52 +/- 11%, and Kfc +63 +/- 20%. The food-induced increases in oxygen uptake and Kfc after SQ 29548 were significantly greater than those induced before the blocking of TxA2-endoperoxide receptors by SQ 29548. Our study indicates that endogenous thromboxane does not play a role in regulating jejunal blood flow, capillary filtration, and oxygen uptake under resting conditions. However, it plays a role in limiting the food-induced increases in jejunal oxygen uptake and capillary exchange capacity without influencing the food-induced hyperemia.

  3. Hypersensitivity to thromboxane receptor mediated cerebral vasomotion and CBF oscillations during acute NO-deficiency in rats.

    Directory of Open Access Journals (Sweden)

    Béla Horváth

    Full Text Available BACKGROUND: Low frequency (4-12 cpm spontaneous fluctuations of the cerebrovascular tone (vasomotion and oscillations of the cerebral blood flow (CBF have been reported in diseases associated with endothelial dysfunction. Since endothelium-derived nitric oxide (NO suppresses constitutively the release and vascular effects of thromboxane A(2 (TXA(2, NO-deficiency is often associated with activation of thromboxane receptors (TP. In the present study we hypothesized that in the absence of NO, overactivation of the TP-receptor mediated cerebrovascular signaling pathway contributes to the development of vasomotion and CBF oscillations. METHODOLOGY/PRINCIPAL FINDINGS: Effects of pharmacological modulation of TP-receptor activation and its downstream signaling pathway have been investigated on CBF oscillations (measured by laser-Doppler flowmetry in anesthetized rats and vasomotion (measured by isometric tension recording in isolated rat middle cerebral arteries, MCAs both under physiological conditions and after acute inhibition of NO synthesis. Administration of the TP-receptor agonist U-46619 (1 µg/kg i.v. to control animals failed to induce any changes of the systemic or cerebral circulatory parameters. Inhibition of the NO synthesis by nitro-L-arginine methyl ester (L-NAME, 100 mg/kg i.v. resulted in increased mean arterial blood pressure and a decreased CBF accompanied by appearance of CBF-oscillations with a dominant frequency of 148±2 mHz. U-46619 significantly augmented the CBF-oscillations induced by L-NAME while inhibition of endogenous TXA(2 synthesis by ozagrel (10 mg/kg i.v. attenuated it. In isolated MCAs U-46619 in a concentration of 100 nM, which induced weak and stable contraction under physiological conditions, evoked sustained vasomotion in the absence of NO, which effect could be completely reversed by inhibition of Rho-kinase by 10 µM Y-27632. CONCLUSION/SIGNIFICANCE: These results suggest that hypersensitivity of the TP

  4. Radioimmunological thromboxane concentrations in arterial blood of cigarette smokers and hypertensive subjects

    International Nuclear Information System (INIS)

    Krause, F.J.

    1987-01-01

    Thromboxane concentrations were investigated in the arterial plasma of 79 patients (24 smokers, 23 nonsmokers, 16 hypertensives, 16 normotensives) with periphered obstructive arterial disease. The thromboxane investigation was made by radioimmunoassay, whose realization was modified. The results indicate that nonsmokers have significantly lower thromboxane levels than smokers, whereas there is no statistically significant difference between hypertensives and normotensives. The findings coincide with the increased risk for arteriosclerosis of smokers, that doesn't work for hypertensives. (orig.) [de

  5. Plasma thromboxane B2 levels in horses experimentally infected with Strongylus vulgaris.

    Science.gov (United States)

    Cambridge, H; Reynoldson, J A; Dunsmore, J D

    1989-06-01

    Plasma thromboxane B2 (TXB2) the stable inactive metabolite of thromboxane A2 (TXA2), was measured daily by specific radioimmunoassay in three groups of animals before and after experimental infection with Strongylus vulgaris. Infection of four 'parasite naive' foals produced a typical acute syndrome with intermittent but statistically insignificant rises in TXB2 levels. Interpretation of results was complicated by the presence of a non-septic peritonitis associated with implantation of the foals with electrodes for recording myoelectrical activity. In two foals of similar age, with some natural exposure to S. vulgaris, there was little or no clinical response to infection and increases in TXB2 were absent. Baseline levels were also much lower, indicating that the peritonitis may have affected the results obtained in the first group of foals. Severe mesenteric arteritis was confirmed at necropsy in all six foals. A third group of yearling horses, all with natural exposure to the parasite, were generally resistant to infection. One animal developed arteritis with clinical signs of diarrhoea and mild colic, and also showed intermittent increases in TXB2. The mean plasma TXB2 level after infection was significantly higher than in the control period, although absolute levels were lower than those recorded in the 'parasite naive' foals. Other animals in this group had low TXB2 levels and minimal arteritis was found at necropsy. These results indicate that although infection appears to have an effect on plasma TXB2, the changes are inconsistent and not reliable indicators of the presence of verminous arteritis. The results also confirm the difficulty in establishing infection and the variability of the response in animals with previous exposure.

  6. Adenosine A2A Receptor Modulates the Activity of Globus Pallidus Neurons in Rats

    Directory of Open Access Journals (Sweden)

    Hui-Ling Diao

    2017-11-01

    Full Text Available The globus pallidus is a central nucleus in the basal ganglia motor control circuit. Morphological studies have revealed the expression of adenosine A2A receptors in the globus pallidus. To determine the modulation of adenosine A2A receptors on the activity of pallidal neurons in both normal and parkinsonian rats, in vivo electrophysiological and behavioral tests were performed in the present study. The extracellular single unit recordings showed that micro-pressure administration of adenosine A2A receptor agonist, CGS21680, regulated the pallidal firing activity. GABAergic neurotransmission was involved in CGS21680-induced modulation of pallidal neurons via a PKA pathway. Furthermore, application of two adenosine A2A receptor antagonists, KW6002 or SCH442416, mainly increased the spontaneous firing of pallidal neurons, suggesting that endogenous adenosine system modulates the activity of pallidal neurons through adenosine A2A receptors. Finally, elevated body swing test (EBST showed that intrapallidal microinjection of adenosine A2A receptor agonist/antagonist induced ipsilateral/contralateral-biased swing, respectively. In addition, the electrophysiological and behavioral findings also revealed that activation of dopamine D2 receptors by quinpirole strengthened KW6002/SCH442416-induced excitation of pallidal activity. Co-application of quinpirole with KW6002 or SCH442416 alleviated biased swing in hemi-parkinsonian rats. Based on the present findings, we concluded that pallidal adenosine A2A receptors may be potentially useful in the treatment of Parkinson's disease.

  7. A2A adenosine receptor ligand binding and signalling is allosterically modulated by adenosine deaminase.

    Science.gov (United States)

    Gracia, Eduard; Pérez-Capote, Kamil; Moreno, Estefanía; Barkešová, Jana; Mallol, Josefa; Lluís, Carme; Franco, Rafael; Cortés, Antoni; Casadó, Vicent; Canela, Enric I

    2011-05-01

    A2ARs (adenosine A2A receptors) are highly enriched in the striatum, which is the main motor control CNS (central nervous system) area. BRET (bioluminescence resonance energy transfer) assays showed that A2AR homomers may act as cell-surface ADA (adenosine deaminase; EC 3.5.4.4)-binding proteins. ADA binding affected the quaternary structure of A2ARs present on the cell surface. ADA binding to adenosine A2ARs increased both agonist and antagonist affinity on ligand binding to striatal membranes where these proteins are co-expressed. ADA also increased receptor-mediated ERK1/2 (extracellular-signal-regulated kinase 1/2) phosphorylation. Collectively, the results of the present study show that ADA, apart from regulating the concentration of extracellular adenosine, may behave as an allosteric modulator that markedly enhances ligand affinity and receptor function. This powerful regulation may have implications for the physiology and pharmacology of neuronal A2ARs.

  8. NCS-1 associates with adenosine A2A receptors and modulates receptor function

    Directory of Open Access Journals (Sweden)

    Gemma eNavarro

    2012-04-01

    Full Text Available Modulation of G protein-coupled receptor (GPCR signalling by local changes in intracellular calcium concentration is an established function of Calmodulin which is known to interact with many GPCRs. Less is known about the functional role of the closely related neuronal EF-hand Ca2+-sensor proteins that frequently associate with calmodulin targets with different functional outcome. In the present study we aimed to investigate if a target of calmodulin – the A2A adenosine receptor, is able to associate with two other neuronal calcium binding proteins, namely NCS-1 and caldendrin. Using bioluminescence resonance energy transfer and co-immunoprecipitation experiments we show the existence of A2A - NCS-1 complexes in living cells whereas caldendrin did not associate with A2A receptors under the conditions tested. Interestingly, NCS-1 binding modulated downstream A2A receptor intracellular signalling in a Ca2+-dependent manner. Taken together this study provides further evidence that neuronal Ca2+-sensor proteins play an important role in modulation of GPCR signalling.

  9. Active Oxygen Metabolites and Thromboxane in Phorbol Myristate Acetate Toxicity to the Isolated, Perfused Rat Lung.

    Science.gov (United States)

    Carpenter, Laurie Jean

    When administered intravenously or intratracheally to rats, rabbits and sheep, phorbol myristate acetate (PMA) produces changes in lung morphology and function are similar to those seen in humans with the adult respiratory distress syndrome (ARDS). Therefore, it is thought that information about the mechanism of ARDS development can be gained from experiments using PMA-treated animals. Currently, the mechanisms by which PMA causes pneumotoxicity are unknown. Results from other studies in rabbits and in isolated, perfused rabbit lungs suggest that PMA-induced lung injury is mediated by active oxygen species from neutrophils (PMN), whereas studies in sheep and rats suggest that PMN are not required for the toxic response. The role of PMN, active oxygen metabolites and thromboxane (TxA_2) in PMA-induced injury to isolated, perfused rat lungs (IPLs) was examined in this thesis. To determine whether PMN were required for PMA to produce toxicity to the IPL, lungs were perfused for 30 min with buffer containing various concentrations of PMA (in the presence or absence of PMN). When concentrations >=q57 ng/ml were added to medium devoid of added PMN, perfusion pressure and lung weight increased. When a concentration of PMA (14-28 ng/ml) that did not by itself cause lungs to accumulate fluid was added to the perfusion medium containing PMN (1 x 10 ^8), perfusion pressure increased, and lungs accumulated fluid. These results indicate that high concentrations of PMA produce lung injury which is independent of PMN, whereas injury induced by lower concentrations is PMN-dependent. To examine whether active oxygen species were involved in mediating lung injury induced by PMA and PMN, lungs were coperfused with the oxygen radical scavengers SOD and/or catalase. Coperfusion with either or both of these enzymes totally protected lungs against injury caused by PMN and PMA. These results suggest that active oxygen species (the hydroxyl radical in particular), mediate lung injury in

  10. Effect of acetyl salicylic acid on increased production of thromboxane after aortic graft surgery.

    Science.gov (United States)

    Lewin, J; Swedenborg, J; Egberg, N; Vesterqvist, O; Green, K

    1989-06-01

    Contact between blood and foreign surfaces, e.g. vascular grafts, causes activation and release of platelets. One consequence of platelet activation is production of thromboxane A2 (TxA2). The physiological effects of TxA2, i.e. platelet aggregation and vaso-constriction are counteracted by another prostanoid, prostacyclin (PGI2). Acetylsalicylic acid (ASA) causes a longlasting inhibition of platelet TxA2 production and a more shortlasting inhibition of PGI2 production. The present study examines TxA2 and PGI2 synthesis in patients receiving synthetic arterial grafts, some of which were treated with ASA. The prostanoid synthesis was evaluated by measurement of their main urinary metabolites with gas chromatography-mass spectrometry. Platelet release was evaluated by measurements of beta-thromboglobulin (beta-TG) and the plasma coagulation by measurements of fibrinopeptide A (FPA). These compounds were also measured in urine in order to avoid artifacts caused by activation of platelets and plasma coagulation during blood sampling. Following replacement of the abdominal aorta with a synthetic vascular graft there was a marked increase in the synthesis of TxA2 and PGI2. Increased levels of beta-TG and FPA were also demonstrated. Administration of ASA on the first and second postoperative days significantly reduced the synthesis of TxA2 but caused no significant effects on the other parameters measured. It is concluded that ASA may be beneficial in the postoperative period since it counteracts TxA2 with vasoconstricting and platelet aggregating properties but leaves PGI2 with vasodilating and antiaggregating properties relatively uneffected.

  11. Stereoselective inhibition of thromboxane-induced coronary vasoconstriction by 1,4-dihydropyridine calcium channel antagonists

    International Nuclear Information System (INIS)

    Eltze, M.; Boer, R.; Sanders, K.H.; Boss, H.; Ulrich, W.R.; Flockerzi, D.

    1990-01-01

    The biological activity of the (+)-S- and (-)-R-enantiomers of niguldipine, of the (-)-S- and (+)-R-enantiomers of felodipine and nitrendipine, and of rac-nisoldipine and rac-nimodipine was investigated in vitro and in vivo. Inhibition of coronary vasoconstriction due to the thromboxane A2 (TxA2)-mimetic U-46619 in guinea pig Langendorff hearts, displacement of (+)-[ 3 H]isradipine from calcium channel binding sites of guinea pig skeletal muscle T-tubule membranes, and blood pressure reduction in spontaneously hypertensive rats were determined. The enantiomers were obtained by stereoselective synthesis. Cross-contamination was less than 0.5% for both S- and R-enantiomers of niguldipine and nitrendipine and less than 1% for those of felodipine. From the doses necessary for a 50% inhibition of coronary vasoconstriction, stereoselectivity ratios for (+)-(S)-/(-)-(R)-niguldipine, (-)-(S)-/(+)-(R)-felodipine, and (-)-(S)-/(+)-(R)-nitrendipine of 28, 13, and 7, respectively, were calculated. The potency ratio rac-nisoldipine/rac-nimodipine was 3.5. Ratios obtained from binding experiments and antihypertensive activity were (+)-(S)-/(-)-(R)-niguldipine = 45 and 35, (-)-(S)-/(+)-(R)-felodipine = 12 and 13, (-)-(S)-/(+)-(R)-nitrendipine = 8 and 8, and rac-nisoldipine/rac-nimodipine = 8 and 7, respectively. Highly significant correlations were found between the in vitro potency of the substances to prevent U-46619-induced coronary vasoconstriction and their affinity for calcium channel binding sites as well as their antihypertensive activity

  12. Design of a 2.5MW(e) biomass gasification power generation module

    Energy Technology Data Exchange (ETDEWEB)

    McLellan, R.

    2000-07-01

    The purpose of this contract was to produce a detailed process and mechanical design of a gasification and gas clean up system for a 2.5MW(e) power generation module based on the generation of electrical power from a wood chip feed stock. The design is to enable the detailed economic evaluation of the process and to verify the technical performance data provided by the pilot plant programme. Detailed process and equipment design also assists in the speed at which the technology can be implemented into a demonstration project. (author)

  13. Impaired thromboxane receptor dimerization reduces signaling efficiency: A potential mechanism for reduced platelet function in vivo.

    Science.gov (United States)

    Capra, Valérie; Mauri, Mario; Guzzi, Francesca; Busnelli, Marta; Accomazzo, Maria Rosa; Gaussem, Pascale; Nisar, Shaista P; Mundell, Stuart J; Parenti, Marco; Rovati, G Enrico

    2017-01-15

    Thromboxane A 2 is a potent mediator of inflammation and platelet aggregation exerting its effects through the activation of a G protein-coupled receptor (GPCR), termed TP. Although the existence of dimers/oligomers in Class A GPCRs is widely accepted, their functional significance still remains controversial. Recently, we have shown that TPα and TPβ homo-/hetero-dimers interact through an interface of residues in transmembrane domain 1 (TM1) whose disruption impairs dimer formation. Here, biochemical and pharmacological characterization of this dimer deficient mutant (DDM) in living cells indicates a significant impairment in its response to agonists. Interestingly, two single loss-of-function TPα variants, namely W29C and N42S recently identified in two heterozygous patients affected by bleeding disorders, match some of the residues mutated in our DDM. These two naturally occurring variants display a reduced potency to TP agonists and are characterized by impaired dimer formation in transfected HEK-293T cells. These findings provide proofs that lack of homo-dimer formation is a crucial process for reduced TPα function in vivo, and might represent one molecular mechanism through which platelet TPα receptor dysfunction affects the patient(s) carrying these mutations. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Thermodynamics and structural analysis of positive allosteric modulation of the ionotropic glutamate receptor GluA2

    DEFF Research Database (Denmark)

    Krintel, Christian; Frydenvang, Karla; Olsen, Lars

    2012-01-01

    Positive allosteric modulators of the ionotropic glutamate receptor-2 (GluA2) are promising compounds for the treatment of cognitive disorders, e.g. Alzheimer's disease. These modulators bind within the dimer interface of the ligand-binding domain and stabilize the agonist-bound conformation slow...

  15. Glutamate signalling and secretory phospholipase A2 modulate the release of arachidonic acid from neuronal membranes

    DEFF Research Database (Denmark)

    Rodriguez De Turco, Elena B; Jackson, Fannie R; DeCoster, Mark A

    2002-01-01

    The lipid mediators generated by phospholipases A(2) (PLA(2)), free arachidonic acid (AA), eicosanoids, and platelet-activating factor, modulate neuronal activity; when overproduced, some of them become potent neurotoxins. We have shown, using primary cortical neuron cultures, that glutamate...... and secretory PLA(2) (sPLA(2)) from bee venom (bv sPLA(2)) and Taipan snake venom (OS2) elicit synergy in inducing neuronal cell death. Low concentrations of sPLA(2) are selective ligands of cell-surface sPLA(2) receptors. We investigated which neuronal arachidonoyl phospholipids are targeted by glutamate......) and in minor changes in other phospholipids. A similar profile, although of greater magnitude, was observed 20 hr posttreatment. Glutamate (80 microM) induced much less mobilization of (3)H-AA than did sPLA(2) and resulted in a threefold greater degradation of (3)H-AA PE than of (3)H-AA PC by 20 hr...

  16. Study of exon 12 polymorphism of the human thromboxane synthase (CYP5A1) gene in Egyptian stroke patients

    International Nuclear Information System (INIS)

    Soliman, S.E.T.; Zaater, M.K.

    2010-01-01

    Thromboxane synthase (CYP5A1) catalyzes the conversion of prostaglandin H2 to thromboxane A2, a potent mediator of platelet aggregation, vasoconstriction and bronchoconstriction. It has been implicated in the patho-physiological process of a variety of diseases, such as atherosclerosis, myocardial infarction, stroke and asthma. On the basis of the hypothesis that variations of the CYP5A1 gene may play an important role in human diseases, we performed screening for the prevalence of exon12 polymorphism of the human Thromboxane synthase (CYP5A1) gene among Egyptian normal and stroke patients. Using sequence-specific PCR, we examined the allelic prevalence in 70 Egyptian patients with ischemic strokes and in 70 controls. In addition, we compared the CYP5A1 allelic prevalence in 30 patients with stroke recurrence despite Aspirin use, in comparison with patients who have not experienced recurrent stroke while taking Aspirin. The frequencies of the CYP5A1*9 mutant (substitution of guanine by adenine near the heme-binding catalytic domain) and of the wild-type allele were 0.197(19.7%) and 0.803 (80.3%) respectively; they did not differ significantly between stroke patients and controls. The CYP5A1*9 mutant was significantly more prevalent among stroke patients with history of previous cerebrovascular attacks; even after adjusting for the common risk factors for cardiovascular disease (odds ratio (OR)1.73, 95%, confidence interval ( CI) 1.10-2.73; p=0.017). Among stroke patients, the presence of the CYP5A1 wild type allele was more frequent among the hypertensives (OR 1.68, 95% CI, 1.01-2.79; p=0.045), and less frequent among the diabetics (OR 0.55, 95%, CI 0.36-0.84; p=0.006). Also among stroke patients, the CYP5A1*9 mutant was significantly more prevalent among those, who failed secondary Aspirin prophylaxis compared to those with successful secondary Aspirin prophylaxis (OR 1.49, 95%, CI 1.06-2.11). This study provides evidence for high prevalence of the CYP5A1*9 mutant

  17. Protein kinase C-related kinase 1 and 2 play an essential role in thromboxane-mediated neoplastic responses in prostate cancer

    OpenAIRE

    O'Sullivan, Aine G.; Mulvaney, Eamon P.; Hyland, Paula B.; Kinsella, B. Therese

    2015-01-01

    The prostanoid thromboxane (TX) A2 is increasingly implicated in neoplastic progression, including prostate cancer (PCa). Mechanistically, we recently identified protein kinase C-related kinase (PRK) 1 as a functional interactant of both the TP? and TP? isoforms of the human T prostanoid receptor (TP). The interaction with PRK1 was not only essential for TP?/TP?-induced PCa cell migration but also enabled the TXA2-TP axis to induce phosphorylation of histone H3 at Thr11 (H3Thr11), an epigenet...

  18. Inhibition of thromboxane synthase induces lung cancer cell death via increasing the nuclear p27

    International Nuclear Information System (INIS)

    Leung, Kin Chung; Hsin, Michael K.Y.; Chan, Joey S.Y.; Yip, Johnson H.Y.; Li, Mingyue; Leung, Billy C.S.; Mok, Tony S.K.; Warner, Timothy D.; Underwood, Malcolm J.; Chen, George G.

    2009-01-01

    The role of thromboxane in lung carcinogenesis is not clearly known, though thromboxane B2 (TXB 2 ) level is increased and antagonists of thromboxane receptors or TXA2 can induce apoptosis of lung cancer cells. p27, an atypical tumor suppressor, is normally sequestered in the nucleus. The increased nuclear p27 may result in apoptosis of tumor cells. We hypothesize that the inhibition of thromboxane synthase (TXS) induces the death of lung cancer cells and that such inhibition is associated with the nuclear p27 level. Our experiment showed that the inhibition of TXS significantly induced the death or apoptosis in lung cancer cells. The activity of TXS was increased in lung cancer. The nuclear p27 was remarkably reduced in lung cancer tissues. The inhibition of TXS caused the cell death and apoptosis of lung cancer cells, likely via the elevation of the nuclear p27 since the TXS inhibition promoted the nuclear p27 level and the inhibition of p27 by its siRNA recovered the cell death induced by TXS inhibition. Collectively, lung cancer cells produce high levels of TXB 2 but their nuclear p27 is markedly reduced. The inhibition of TXS results in the p27-related induction of cell death in lung cancer cells.

  19. Inhibition of thromboxane synthase induces lung cancer cell death via increasing the nuclear p27

    Energy Technology Data Exchange (ETDEWEB)

    Leung, Kin Chung; Hsin, Michael K.Y.; Chan, Joey S.Y.; Yip, Johnson H.Y.; Li, Mingyue; Leung, Billy C.S. [Department of Surgery, The Chinese University of Hong Kong, Shatin, New Territories (Hong Kong); Mok, Tony S.K. [Department of Clinical Oncology, The Chinese University of Hong Kong, Shatin, New Territories (Hong Kong); Warner, Timothy D. [The William Harvey Research Institute, Queen Mary University of London, London (United Kingdom); Underwood, Malcolm J. [Department of Surgery, The Chinese University of Hong Kong, Shatin, New Territories (Hong Kong); Chen, George G., E-mail: gchen@cuhk.edu.hk [Department of Surgery, The Chinese University of Hong Kong, Shatin, New Territories (Hong Kong)

    2009-10-15

    The role of thromboxane in lung carcinogenesis is not clearly known, though thromboxane B2 (TXB{sub 2}) level is increased and antagonists of thromboxane receptors or TXA2 can induce apoptosis of lung cancer cells. p27, an atypical tumor suppressor, is normally sequestered in the nucleus. The increased nuclear p27 may result in apoptosis of tumor cells. We hypothesize that the inhibition of thromboxane synthase (TXS) induces the death of lung cancer cells and that such inhibition is associated with the nuclear p27 level. Our experiment showed that the inhibition of TXS significantly induced the death or apoptosis in lung cancer cells. The activity of TXS was increased in lung cancer. The nuclear p27 was remarkably reduced in lung cancer tissues. The inhibition of TXS caused the cell death and apoptosis of lung cancer cells, likely via the elevation of the nuclear p27 since the TXS inhibition promoted the nuclear p27 level and the inhibition of p27 by its siRNA recovered the cell death induced by TXS inhibition. Collectively, lung cancer cells produce high levels of TXB{sub 2} but their nuclear p27 is markedly reduced. The inhibition of TXS results in the p27-related induction of cell death in lung cancer cells.

  20. In situ microdialysis of intramuscular prostaglandin and thromboxane in contracting skeletal muscle in humans

    DEFF Research Database (Denmark)

    Karamouzis, M; Langberg, Henning; Skovgaard, D

    2001-01-01

    Arachidonic acid metabolites, especially prostacyclin I2, are regulators of vascular tone, and may be released from contracting muscle. In the present study, the influence of exercise on accumulation of prostaglandins and thromboxane in skeletal muscle was determined by the use of microdialysis...

  1. Lack of Thromboxane Synthase Prevents Hypertension and Fetal Growth Restriction after High Salt Treatment during Pregnancy.

    Directory of Open Access Journals (Sweden)

    Chen-Hsueh Pai

    Full Text Available Preeclampsia (PE is a potentially fatal pregnancy-related hypertensive disorder characterized by poor placenta development that can cause fetal growth restriction. PE-associated pathologies, including thrombosis, hypertension, and impaired placental development, may result from imbalances between thromboxane A2 (TXA2 and prostacyclin. Low-dose aspirin, which selectively inhibits TXA2 production, is used to prevent high-risk PE. However, the role of TXA2 in aspirin-mediated protective effects in women with PE is not understood fully. In this study, we examined the role of prostanoids in PE using human samples and an induced PE mouse model. We demonstrated that the administration of salted drinking water (2.7% NaCl to wild-type mice resulted in elevated placental TXA2 synthase (TXAS and plasma TXA2, but not prostacyclin, levels, which was also found in our clinical PE placenta samples. The high salt-treated wild-type pregnant mice had shown unchanged maternal body weight, hypertension (MAP increase 15 mmHg, and decreased pup weight (~50% and size (~24%, but these adverse effects were ameliorated in TXAS knockout (KO mice. Moreover, increased expression of interleukin-1β and downstream phosphorylated-p38-mitogen-activated protein kinase were concordant with apoptosis induction in the placentas of salt water-treated wild-type mice. These alterations were not observed in TXAS KO mice. Together, our data suggest that TXA2 depletion has anti-PE effects due to the prevention of hypertension and placental damage through downregulation of the interleukin-1β pathway.

  2. Platelet dysfunction associated with the novel Trp29Cys thromboxane A₂ receptor variant.

    Science.gov (United States)

    Mumford, A D; Nisar, S; Darnige, L; Jones, M L; Bachelot-Loza, C; Gandrille, S; Zinzindohoue, F; Fischer, A-M; Mundell, S J; Gaussem, P

    2013-03-01

    Genetic variations that affect the structure of the thromboxane A2 receptor (TP receptor) provide insights into the function of this key platelet and vascular receptor, but are very rare in unselected populations. To determine the functional consequences of the TP receptor Trp29Cys (W29C) substitution. We performed a detailed phenotypic analysis of an index case (P1) with reduced platelet aggregation and secretion responses to TP receptor pathway activators, and a heterozygous TP receptor W29C substitution. An analysis of the variant W29C TP receptor expressed in heterologous cells was performed. Total TP receptor expression in platelets from P1 was similar to that of controls, but there was reduced maximum binding and reduced affinity of binding to the TP receptor antagonist [(3) H]SQ29548. HEK293 cells transfected with W29C TP receptor cDNA showed similar total TP receptor expression to wild-type (WT) controls. However, the TP receptor agonist U46619 was less potent at inducing rises in cytosolic free Ca(2+) in HEK293 cells expressing the W29C TP receptor than in WT controls, indicating reduced receptor function. Immunofluorescence microscopy and cell surface ELISA showed intracellular retention and reduced cell surface expression of the W29C TP receptor in HEK293 cells. Consistent with the platelet phenotype, both maximum binding and the affinity of binding of [(3) H]SQ29548 to the W29C TP receptor were reduced compared to WT controls. These findings extend the phenotypic description of the very rare disorder TP receptor deficiency, and show that the W29C substitution reduces TP receptor function by reducing surface receptor expression and by disrupting ligand binding. © 2012 International Society on Thrombosis and Haemostasis.

  3. Examination of thromboxane synthase as a prognostic factor and therapeutic target in non-small cell lung cancer.

    LENUS (Irish Health Repository)

    Cathcart, Mary-Clare

    2011-03-01

    Thromboxane synthase (TXS) metabolises prostaglandin H2 into thromboxanes, which are biologically active on cancer cells. TXS over-expression has been reported in a range of cancers, and associated with a poor prognosis. TXS inhibition induces cell death in-vitro, providing a rationale for therapeutic intervention. We aimed to determine the expression profile of TXS in NSCLC and if it is prognostic and\\/or a survival factor in the disease.

  4. Platelet deposition in rat heart allografts and the effect of a thromboxane receptor antagonist

    International Nuclear Information System (INIS)

    Foegh, M.L.; Khirabadi, B.S.; Ramwell, P.W.

    1986-01-01

    The effect of a thromboxane antagonist, L640,035 on platelet deposition in heart allografts was studied. Twenty Lewis rats received heterotopic allografts from Lewis x Brown-Norway F1 hybrid. All recipients received azathioprine (5 mg/kg/day). The rats were divided into three groups. Groups II and III were also treated daily with either the vehicle for L640,035 or L640,035 respectively. Syngeneic indium-111-labeled platelet deposition was determined in the allograft and the native heart at 6, 9, and 13 days after transplantation; group III was studied on the sixth and ninth day only. A rapidly increasing platelet deposition was seen in allografts from rats given azathioprine; whereas the thromboxane antagonist prevented the increase in platelet deposition on the ninth day

  5. Flow transients induced on a 2D airfoil by pulse-modulated actuation

    Energy Technology Data Exchange (ETDEWEB)

    Amitay, Michael [Rensselaer Polytechnic Institute, Mechanical, Aerospace and Nuclear Engineering, Troy, NY (United States); Glezer, Ari [Georgia Institute of Technology, Woodruff School of Mechanical Engineering, Atlanta, GA (United States)

    2006-02-01

    The transitory response of the flow over a stalled, 2D airfoil to a momentary synthetic jet actuation that is realized by low-duty cycle amplitude modulation of the actuator's resonant waveform is investigated experimentally using hot-wire anemometry and flow visualization. The pulse-like actuation results in the shedding of large vortical structures and a momentary flow attachment. (orig.)

  6. A2BR Adenosine Receptor Modulates Sweet Taste in Circumvallate Taste Buds

    Science.gov (United States)

    Yang, Dan; Shultz, Nicole; Vandenbeuch, Aurelie; Ravid, Katya; Kinnamon, Sue C.; Finger, Thomas E.

    2012-01-01

    In response to taste stimulation, taste buds release ATP, which activates ionotropic ATP receptors (P2X2/P2X3) on taste nerves as well as metabotropic (P2Y) purinergic receptors on taste bud cells. The action of the extracellular ATP is terminated by ectonucleotidases, ultimately generating adenosine, which itself can activate one or more G-protein coupled adenosine receptors: A1, A2A, A2B, and A3. Here we investigated the expression of adenosine receptors in mouse taste buds at both the nucleotide and protein expression levels. Of the adenosine receptors, only A2B receptor (A2BR) is expressed specifically in taste epithelia. Further, A2BR is expressed abundantly only in a subset of taste bud cells of posterior (circumvallate, foliate), but not anterior (fungiform, palate) taste fields in mice. Analysis of double-labeled tissue indicates that A2BR occurs on Type II taste bud cells that also express Gα14, which is present only in sweet-sensitive taste cells of the foliate and circumvallate papillae. Glossopharyngeal nerve recordings from A2BR knockout mice show significantly reduced responses to both sucrose and synthetic sweeteners, but normal responses to tastants representing other qualities. Thus, our study identified a novel regulator of sweet taste, the A2BR, which functions to potentiate sweet responses in posterior lingual taste fields. PMID:22253866

  7. A2BR adenosine receptor modulates sweet taste in circumvallate taste buds.

    Directory of Open Access Journals (Sweden)

    Shinji Kataoka

    Full Text Available In response to taste stimulation, taste buds release ATP, which activates ionotropic ATP receptors (P2X2/P2X3 on taste nerves as well as metabotropic (P2Y purinergic receptors on taste bud cells. The action of the extracellular ATP is terminated by ectonucleotidases, ultimately generating adenosine, which itself can activate one or more G-protein coupled adenosine receptors: A1, A2A, A2B, and A3. Here we investigated the expression of adenosine receptors in mouse taste buds at both the nucleotide and protein expression levels. Of the adenosine receptors, only A2B receptor (A2BR is expressed specifically in taste epithelia. Further, A2BR is expressed abundantly only in a subset of taste bud cells of posterior (circumvallate, foliate, but not anterior (fungiform, palate taste fields in mice. Analysis of double-labeled tissue indicates that A2BR occurs on Type II taste bud cells that also express Gα14, which is present only in sweet-sensitive taste cells of the foliate and circumvallate papillae. Glossopharyngeal nerve recordings from A2BR knockout mice show significantly reduced responses to both sucrose and synthetic sweeteners, but normal responses to tastants representing other qualities. Thus, our study identified a novel regulator of sweet taste, the A2BR, which functions to potentiate sweet responses in posterior lingual taste fields.

  8. A2BR adenosine receptor modulates sweet taste in circumvallate taste buds.

    Science.gov (United States)

    Kataoka, Shinji; Baquero, Arian; Yang, Dan; Shultz, Nicole; Vandenbeuch, Aurelie; Ravid, Katya; Kinnamon, Sue C; Finger, Thomas E

    2012-01-01

    In response to taste stimulation, taste buds release ATP, which activates ionotropic ATP receptors (P2X2/P2X3) on taste nerves as well as metabotropic (P2Y) purinergic receptors on taste bud cells. The action of the extracellular ATP is terminated by ectonucleotidases, ultimately generating adenosine, which itself can activate one or more G-protein coupled adenosine receptors: A1, A2A, A2B, and A3. Here we investigated the expression of adenosine receptors in mouse taste buds at both the nucleotide and protein expression levels. Of the adenosine receptors, only A2B receptor (A2BR) is expressed specifically in taste epithelia. Further, A2BR is expressed abundantly only in a subset of taste bud cells of posterior (circumvallate, foliate), but not anterior (fungiform, palate) taste fields in mice. Analysis of double-labeled tissue indicates that A2BR occurs on Type II taste bud cells that also express Gα14, which is present only in sweet-sensitive taste cells of the foliate and circumvallate papillae. Glossopharyngeal nerve recordings from A2BR knockout mice show significantly reduced responses to both sucrose and synthetic sweeteners, but normal responses to tastants representing other qualities. Thus, our study identified a novel regulator of sweet taste, the A2BR, which functions to potentiate sweet responses in posterior lingual taste fields.

  9. Evidence that the angiotensin at 2-receptor agonist compound 21 is also a low affinity thromboxane TXA2-receptor antagonist

    DEFF Research Database (Denmark)

    Fredgart, M.; Leurgans, T.; Stenelo, M.

    2015-01-01

    Objective: The objective of this study was to test whether Compound 21 (C21), a high-affinity, non-peptide angiotensinAT2-receptor agonist, is also an antagonist of thromboxane A2 (TXA2) receptors thus reducing both vasoconstriction and platelet aggregation. Design and method: Binding of C21...... to the TXA2 receptor was determined by TBXA2R Arrestin Biosensor Assay. Mouse mesenteric arteries were mounted in wire myographs, and responses to increasing concentrations of C21 (1nM- 10muM) were recorded during submaximal contractions with 0.1muM U46619 (TXA2 analogue) or 1muMphenylephrine. To control for......AT2-receptor specificity, arteries were pre-incubated with the AT2-receptor antagonist PD123319 (10muM), or mesenteric arteries from AT2-receptor knock-out (AT2R-/y) mice were used. An inhibitory effect of C21 (100nM - 10muM) on U46619 (0,3muM) induced platelet aggregation was examined in whole human...

  10. Adenosine A2A Receptors Modulate Acute Injury and Neuroinflammation in Brain Ischemia

    Directory of Open Access Journals (Sweden)

    Felicita Pedata

    2014-01-01

    Full Text Available The extracellular concentration of adenosine in the brain increases dramatically during ischemia. Adenosine A2A receptor is expressed in neurons and glial cells and in inflammatory cells (lymphocytes and granulocytes. Recently, adenosine A2A receptor emerged as a potential therapeutic attractive target in ischemia. Ischemia is a multifactorial pathology characterized by different events evolving in the time. After ischemia the early massive increase of extracellular glutamate is followed by activation of resident immune cells, that is, microglia, and production or activation of inflammation mediators. Proinflammatory cytokines, which upregulate cell adhesion molecules, exert an important role in promoting recruitment of leukocytes that in turn promote expansion of the inflammatory response in ischemic tissue. Protracted neuroinflammation is now recognized as the predominant mechanism of secondary brain injury progression. A2A receptors present on central cells and on blood cells account for important effects depending on the time-related evolution of the pathological condition. Evidence suggests that A2A receptor antagonists provide early protection via centrally mediated control of excessive excitotoxicity, while A2A receptor agonists provide protracted protection by controlling massive blood cell infiltration in the hours and days after ischemia. Focus on inflammatory responses provides for adenosine A2A receptor agonists a wide therapeutic time-window of hours and even days after stroke.

  11. Thermodynamic Characterization of New Positive Allosteric Modulators Binding to the Glutamate Receptor A2 Ligand-Binding Domain

    DEFF Research Database (Denmark)

    Nørholm, Ann-Beth; Francotte, Pierre; Goffin, Eric

    2014-01-01

    , and 5a (5-F) and 5b (6-F) are entropy driven. For 5d (8-F), both quantities were equal in size. Thermodynamic integration (TI) and one-step perturbation (OSP) were used to calculate the relative binding affinity of the modulators. The OSP calculations had a higher predictive power than those from TI......,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides. Measurements of ligand binding by isothermal titration calorimetry (ITC) showed similar binding affinities for the modulator series at the GluA2 LBD but differences in the thermodynamic driving forces. Binding of 5c (7-F) and 6 (no-F) is enthalpy driven......, and combined with the shorter total simulation time, we found the OSP method to be more effective for this setup. Furthermore, from the molecular dynamics simulations, we extracted the enthalpies and entropies, and along with the ITC data, this suggested that the differences in binding free energies...

  12. Effects of the dual TP receptor antagonist and thromboxane synthase inhibitor EV-077 on human endothelial and vascular smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Petri, Marcelo H. [Department of Medicine, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm (Sweden); Tellier, Céline; Michiels, Carine [NARILIS, URBC, University of Namur, Namur (Belgium); Ellertsen, Ingvill [Department of Medicine, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm (Sweden); Dogné, Jean-Michel [Department of Pharmacy, Namur Thrombosis and Hemostasis Center, University of Namur, Namur (Belgium); Bäck, Magnus, E-mail: Magnus.Back@ki.se [Department of Medicine, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm (Sweden)

    2013-11-15

    Highlights: •EV-077 reduced TNF-α induced inflammation in endothelial cells. •The thromboxane mimetic U69915 enhanced vascular smooth muscle cell proliferation. •EV-077 inhibited smooth muscle cell proliferation. -- Abstract: The prothrombotic mediator thromboxane A{sub 2} is derived from arachidonic acid metabolism through the cyclooxygenase and thromboxane synthase pathways, and transduces its effect through the thromboxane prostanoid (TP) receptor. The aim of this study was to determine the effect of the TP receptor antagonist and thromboxane synthase inhibitor EV-077 on inflammatory markers in human umbilical vein endothelial cells and on human coronary artery smooth muscle cell proliferation. To this end, mRNA levels of different proinflammatory mediators were studied by real time quantitative PCR, supernatants were analyzed by enzyme immune assay, and cell proliferation was assessed using WST-1. EV-077 significantly decreased mRNA levels of ICAM-1 and PTX3 after TNFα incubation, whereas concentrations of 6-keto PGF1α in supernatants of endothelial cells incubated with TNFα were significantly increased after EV-077 treatment. Although U46619 did not alter coronary artery smooth muscle cell proliferation, this thromboxane mimetic enhanced the proliferation induced by serum, insulin and growth factors, which was significantly inhibited by EV-077. In conclusion, EV-077 inhibited TNFα-induced endothelial inflammation and reduced the enhancement of smooth muscle cell proliferation induced by a thromboxane mimetic, supporting that the thromboxane pathway may be associated with early atherosclerosis in terms of endothelial dysfunction and vascular hypertrophy.

  13. The purification step is not crucial in EIA measurements of thromboxane B2 and 11-dehydrothromboxane B2 in human plasma.

    Science.gov (United States)

    Sadilkova, Lenka; Paluch, Zoltan; Mottlova, Jirina; Bednar, Frantisek; Alusik, Stefan

    2012-01-01

    Thromboxane B2 (TxB2) and particularly 11-dehydrothromboxane B2 (11-dTxB2) are widely used as prognostic risk markers of platelet activation in cardiovascular diseases. The main errors in TxB2 and 11-dTxB2 determination include either low concentrations of circulating TxB2 (1 - 2 pg/mL) and 11-dTxB2 (0.9 - 4.3 pg/mL) or rather high transiency (mean TxB2 half-life is approximately 5 minutes) as well as an incorrect pre-analytical phase set up. The aim of this study was to investigate the impact of a widely used purification step on the results of enzyme immunosorbent assay (EIA)--based measurement of the two selected thromboxanes. For the purpose of this study, 20 plasma samples (10 healthy donors, 10 patients under treatment with acetylsalicylic acid) were screened for TxB2 and 11-dTxB2 concentrations using commercial competitive EIA kits (Cayman Chemicals, Tallinn, Estonia; Neogen, Lexington, KY, USA) with or without the introduction of the purification procedure. The purification step does not significantly affect the results of EIA measurements of the two of TxA2 metabolites (TxB2, 11-dTxB2) in human plasma. The levels of TxB2 and 11-dTxB2 determined in the plasma samples were not significantly changed (p < 0.05) when the purification step was omitted compared to the purified samples. This study establishes a protocol allowing for reliable and reproducible plasma TxB2 and 11-dTxB2 EIA measurement for routine basic screening of platelet function.

  14. Protein kinase A mediates adenosine A2a receptor modulation of neurotransmitter release via synapsin I phosphorylation in cultured cells from medulla oblongata.

    Science.gov (United States)

    Matsumoto, Joao Paulo Pontes; Almeida, Marina Gomes; Castilho-Martins, Emerson Augusto; Costa, Maisa Aparecida; Fior-Chadi, Debora Rejane

    2014-08-01

    Synaptic transmission is an essential process for neuron physiology. Such process is enabled in part due to modulation of neurotransmitter release. Adenosine is a synaptic modulator of neurotransmitter release in the Central Nervous System, including neurons of medulla oblongata, where several nuclei are involved with neurovegetative reflexes. Adenosine modulates different neurotransmitter systems in medulla oblongata, specially glutamate and noradrenaline in the nucleus tractussolitarii, which are involved in hypotensive responses. However, the intracellular mechanisms involved in this modulation remain unknown. The adenosine A2a receptor modulates neurotransmitter release by activating two cAMP protein effectors, the protein kinase A and the exchange protein activated by cAMP. Therefore, an in vitro approach (cultured cells) was carried out to evaluate modulation of neurotransmission by adenosine A2a receptor and the signaling intracellular pathway involved. Results show that the adenosine A2a receptor agonist, CGS 21680, increases neurotransmitter release, in particular, glutamate and noradrenaline and such response is mediated by protein kinase A activation, which in turn increased synapsin I phosphorylation. This suggests a mechanism of A2aR modulation of neurotransmitter release in cultured cells from medulla oblongata of Wistar rats and suggest that protein kinase A mediates this modulation of neurotransmitter release via synapsin I phosphorylation. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  15. Cumulative inhibitory effect of low-dose aspirin on vascular prostacyclin and platelet thromboxane production in patients with atherosclerosis.

    Science.gov (United States)

    Weksler, B B; Tack-Goldman, K; Subramanian, V A; Gay, W A

    1985-02-01

    The relationship between the antithrombotic and antiplatelet effects of aspirin is complex, since aspirin influences other systems that protect against thrombosis as well as inhibiting platelet function. We investigated possible cumulative effects of low-dose aspirin on vascular production of prostacyclin in patients with documented atherosclerotic cardiovascular disease. Candidates for coronary artery vein graft bypass ingested 20 mg of aspirin daily during the week before surgery, and platelet aggregation, platelet formation of thromboxane A2 (TXA2), aortic and saphenous vein production of prostacyclin (PGI2), and hemostatic status were measured at the time of the bypass surgery. Low-dose aspirin markedly inhibited platelet aggregation responses and reduced TXA2 generation by greater than 90%, effects similar to those observed with much higher doses of aspirin. Both aortic and saphenous vein production of PGI2 were inhibited by 50% compared with PGI2 produced by vascular tissues of control subjects who received no aspirin preoperatively (51 +/- 10 pg 6-keto-PGF1 alpha/mg aortic wet weight [mean +/- SEM] in aspirin-treated subjects vs 130 +/- 16 pg/mg in control subjects, and 71 +/- 8 pg/mg saphenous vein wet weight vs 131 +/- 17 pg/mg). Blood loss at surgery was not significantly increased by preoperative low-dose aspirin as measured by chest tube drainage (754 +/- 229 ml in aspirin-treated subjects vs 645 +/- 271 ml in control subjects), hematocrit nadir (31.2 +/- 1.9% vs 31.8 +/- 1.7%), or transfusions (2.2 +/- 1.3 units of red blood cells vs 2.2 +/- 1.7 units).(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Evaluation of platelet thromboxane radioimmunoassay method to measure platelet life-span: Comparison with /sup 111/indium-platelet method

    International Nuclear Information System (INIS)

    Vallabhajosula, S.; Machac, J.; Badimon, L.; Lipszyc, H.; Goldsmith, S.J.; Fuster, V.

    1985-01-01

    The platelet activation during radiolabeling in vitro with Cr-51 and In-111 may affect the platelet life-span (PLS) in vivo. A new RIA method to measure PLS is being evaluated. Aspirin inhibits platelet thromboxane (TxA/sub 2/) by acetylating cyclooxygenase. The time required for the TxA/sub 2/ levels to return towards control values depends on the rate of new platelets entering circulation and is a measure of PLS. A single dose of aspirin (150mg) was given to 5 normal human subjects. Blood samples were collected for 2 days before aspirin and daily for 10 days. TxA/sub 2/ production in response to endogenous thrombin was studied by allowing 1 ml blood sample to clot at 37 0 C for 90 min. Serum TxB/sub 2/ (stable breakdown product of Tx-A/sub 2/) levels determined by RIA technique. The plot of TxB/sub 2/ levels (% control) against time showed a gradual increase. The PLS calculated by linear regression analysis assuming a 2-day lag period before cyclooxygenase recovery is 9.7 +- 2.37. In the same 5 subjects, platelets from a 50ml blood sample were labeled with /sup 111/In-tropolone in 2 ml autologous plasma. Starting at 1 hr after injection of labeled platelets, 10 blood samples were obtained over a 8 day period. The PLS calculated based on a linear regression analysis is 10.2 +. 1.4. The PLS measured from the rate of platelet disappearance from circulation and the rate of platelet regeneration into circulation are quite comparable in normal subjects. TxA/sub 2/ regeneration RIA may provide a method to measure PLS without administering radioactivity to patient

  17. Hypoxia increases pulmonary arterial thromboxane receptor internalization independent of receptor sensitization.

    Science.gov (United States)

    Fediuk, J; Sikarwar, A S; Lizotte, P P; Hinton, M; Nolette, N; Dakshinamurti, S

    2015-02-01

    Persistent Pulmonary Hypertension of the Newborn (PPHN) is characterized by sustained vasospasm and an increased thromboxane:prostacyclin ratio. Thromboxane (TP) receptors signal via Gαq to mobilize IP3 and Ca(2+), causing pulmonary arterial constriction. We have previously reported increased TP internalization in hypoxic pulmonary arterial (PA) myocytes. Serum-deprived PA myocytes were grown in normoxia (NM) or hypoxia (HM) for 72 h. TP localization was visualized in agonist-naïve and -challenged NM and HM by immunocytochemistry. Pathways for agonist-induced TP receptor internalization were determined by inhibiting caveolin- or clathrin-mediated endocytosis, and caveolar fractionation. Roles of actin and tubulin in TP receptor internalization were assessed using inhibitors of tubulin, actin-stabilizing or -destabilizing agents. PKA, PKC or GRK activation and inhibition were used to determine the kinase responsible for post-agonist receptor internalization. Agonist-naïve HM had decreased cell surface TP, and greater TP internalization after agonist challenge. TP protein did not sort with caveolin-rich fractions. Inhibition of clathrin prevented TP internalization. Both actin-stabilizing and -destabilizing agents prevented TP endocytosis in NM, while normalizing TP internalization in HM. Velocity of TP internalization was unaffected by PKA activity, but PKC activation normalized TP receptor internalization in HM. GRK inhibition had no effect. We conclude that in hypoxic myocytes, TP is internalized faster and to a greater extent than in normoxic controls. Internalization of the agonist-challenged TP requires clathrin, dynamic actin and is sensitive to PKC activity. TP receptor trafficking and signaling in hypoxia are pivotal to understanding increased vasoconstrictor sensitivity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Modulation of short-term social memory in rats by adenosine A1 and A(2A) receptors.

    Science.gov (United States)

    Prediger, Rui D S; Takahashi, Reinaldo N

    2005-03-16

    The recognition of an unfamiliar juvenile rat by an adult rat has been shown to imply short-term memory processes. The present study was designed to examine the role of adenosine receptors in the short-term social memory of rats using the social recognition paradigm. Adenosine (5.0-10.0 mg/kg), the selective adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA, 0.025-0.05 mg/kg) and the selective adenosine A(2A) receptor agonist N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl]adenosine (DPMA, 1.0-5.0 mg/kg), given by i.p. route 30 min before the test, disrupted the juvenile recognition ability of adult rats. This negative effect of adenosine (5.0 mg/kg, i.p.) on social memory was prevented by pretreatment with the non-selective adenosine receptor antagonist caffeine (10.0 mg/kg, i.p.), the adenosine A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 1.0 mg/kg, i.p.) and the adenosine A(2A) antagonist 4-(2-[7-amino-2-{2-furyl}{1,2,4}triazolo-{2,3-a}{1,3,5}triazin-5-yl-amino]ethyl)phenol (ZM241385, 1.0 mg/kg, i.p.). Furthermore, acute administration of caffeine (10.0-30.0 mg/kg, i.p.), DPCPX (1.0-3.0 mg/kg, i.p.) or ZM241385 (0.5-1.0 mg/kg, i.p.) improved the short-term social memory in a specific manner. These results indicate that adenosine modulates the short-term social memory in rats by acting on both A1 and A(2A) receptors, with adenosine receptor agonists and antagonists, respectively, disrupting and enhancing the social memory.

  19. Improvements in Attention and Cardiac Autonomic Modulation After a 2-Weeks Sprint Interval Training Program: A Fidelity Approach

    Directory of Open Access Journals (Sweden)

    Arilson F. M. de Sousa

    2018-03-01

    Full Text Available This study aimed to: (1 investigate the influence of a 2-weeks sprint interval training (SIT program on aerobic capacity, cardiac autonomic control, and components of attention in young healthy university students; and (2 to ascertain whether training fidelity would influence these adaptations. One hundred and nine participants were divided into an experimental (EG and control (CG groups. The EG performed a SIT program that consisted of 6 sessions of 4 × 30 s “all-out” efforts on a cycle ergometer, interspersed with active rests of 4 min. The criterion for fidelity was achieving >90% of estimated maximum heart rate (HR during sprint bouts. After analyses, the EG was divided into HIGH (n = 26 and LOW (n = 46 fidelity groups. Components of attention were assessed using the Attention Network Test (ANT. Aerobic capacity (VO2max was estimated while the sum of skinfolds was determined. Autonomic control of HR was assessed by means of HR variability (HRV and HR complexity at rest and during ANT. Both HIGH and LOW significantly increased aerobic capacity, vagal modulation before and during ANT, and executive control, and decreased body fatness after SIT (p < 0.05. However, only participants from HIGH showed an increase in HR complexity and accuracy in ANT when compared to LOW (p < 0.05. Two weeks of SIT improved executive control, body fatness, aerobic fitness, and autonomic control in university students with better results reported in those individuals who exhibited high fidelity.

  20. Metabolism of 5,6-epoxyeicosatrienoic acid by the human platelet. Formation of novel thromboxane analogs.

    Science.gov (United States)

    Balazy, M

    1991-12-15

    Radiolabeled cis-(+-)-5,6-epoxyeicosatrienoic acid (5(6)-EpETrE) was incubated with a suspension of isolated human platelets in order to study its metabolic fate. The epoxide slowly disappeared from the suspension and was completely metabolized within 30 min. After extraction and analysis by reverse-phase high performance liquid chromatography, seven metabolites were found. Addition of either indomethacin (0.01 mM, cyclooxygenase inhibitor) or BW755C (0.1 mM, cyclooxygenase/lipoxygenase inhibitor) to the incubations blocked the formation of four and six metabolites, respectively, 1,2-Epoxy-3,3,3-trichloropropane (inhibitor of microsomal epoxide hydrolase) failed to inhibit the formation of 5,6-dihydroxyeicosatrienoic acid (5,6-DiHETrE), a hydrolysis product of the precursor 5(6)-EpETrE. The metabolites were characterized by UV spectroscopy, negative ion chemical ionization liquid chromatography/mass spectrometry, gas chromatography/mass spectrometry and, in one instance, coelution with synthetic standard. Three primary platelet metabolites were structurally determined to be 5,6-epoxy-12-hydroxyeicosatrienoic acid, 5,6-epoxy-12-hydroxyheptadecadienoic acid, and a unique bicyclic metabolite, 5-hydroxy-6,9-epoxy-thromboxane B1, which originated from intramolecular hydrolysis of 5,6-epoxythromboxane-B1. This thromboxane analog was partially separated into stereoisomers and coeluted with the racemic synthetic standard in gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry. Three other metabolites were characterized as 5,6,12-trihydroxyeicosatrienoic acid, 5,6,12-trihydroxyheptadecadienoic acid, and 5,6-dihydroxythromboxane-B1, and resulted from the hydrolysis of the corresponding epoxides rather than from the metabolism of 5,6-DiHETrE. The latter was not metabolized by platelet cyclooxygenase or lipoxygenase. The biosynthesis of two cyclooxygenase metabolites indicated the formation of unstable 5,6-epoxythromboxane-A1 as an intermediate

  1. Pressure Modulation of the Enzymatic Activity of Phospholipase A2, A Putative Membrane-Associated Pressure Sensor.

    Science.gov (United States)

    Suladze, Saba; Cinar, Suleyman; Sperlich, Benjamin; Winter, Roland

    2015-10-07

    Phospholipases A2 (PLA2) catalyze the hydrolysis reaction of sn-2 fatty acids of membrane phospholipids and are also involved in receptor signaling and transcriptional pathways. Here, we used pressure modulation of the PLA2 activity and of the membrane's physical-chemical properties to reveal new mechanistic information about the membrane association and subsequent enzymatic reaction of PLA2. Although the effect of high hydrostatic pressure (HHP) on aqueous soluble and integral membrane proteins has been investigated to some extent, its effect on enzymatic reactions operating at the water/lipid interface has not been explored, yet. This study focuses on the effect of HHP on the structure, membrane binding and enzymatic activity of membrane-associated bee venom PLA2, covering a pressure range up to 2 kbar. To this end, high-pressure Fourier-transform infrared and high-pressure stopped-flow fluorescence spectroscopies were applied. The results show that PLA2 binding to model biomembranes is not significantly affected by pressure and occurs in at least two kinetically distinct steps. Followed by fast initial membrane association, structural reorganization of α-helical segments of PLA2 takes place at the lipid water interface. FRET-based activity measurements reveal that pressure has a marked inhibitory effect on the lipid hydrolysis rate, which decreases by 75% upon compression up to 2 kbar. Lipid hydrolysis under extreme environmental conditions, such as those encountered in the deep sea where pressures up to the kbar-level are encountered, is hence markedly affected by HHP, rendering PLA2, next to being a primary osmosensor, a good candidate for a sensitive pressure sensor in vivo.

  2. Thromboxane synthase suppression induces lung cancer cell apoptosis via inhibiting NF-κB

    International Nuclear Information System (INIS)

    Leung, Kin Chung; Li, Ming-Yue; Leung, Billy C.S.; Hsin, Michael K.Y.; Mok, Tony S.K.; Underwood, Malcolm J.; Chen, George G.

    2010-01-01

    Accumulating evidence shows that the inhibition of thromboxane synthase (TXS) induced apoptosis in cancer cells. TXS inhibitor 1-Benzylimidzole (1-BI) can trigger apoptosis in lung cancer cells but the mechanism is not fully defined. In this study, lung cancer cells were treated with 1-BI. In this study, the level of reactive oxygen species (ROS) was measured and NF-κB activity was determined in human lung cancer cells. The roles of ROS and NF-κB in 1-BI-mediated cell death were analyzed. The results showed that 1-BI induced ROS generation but decreased the activity of NF-κB by reducing phosphorylated IκBα (p-IκBα) and inhibiting the translocation of p65 into the nucleus. In contrast to 1-BI, antioxidant N-acetyl cysteine (NAC) stimulated cell proliferation and significantly protected the cells from 1-BI-mediated cell death by neutralizing ROS. Collectively, apoptosis induced by 1-BI is associated with the over-production of ROS and the reduction of NF-κB. Antioxidants can significantly block the inhibitory effect of 1-BI.

  3. Spatiotemporal brain dynamics of emotional face processing modulations induced by the serotonin 1A/2A receptor agonist psilocybin.

    Science.gov (United States)

    Bernasconi, Fosco; Schmidt, André; Pokorny, Thomas; Kometer, Michael; Seifritz, Erich; Vollenweider, Franz X

    2014-12-01

    Emotional face processing is critically modulated by the serotonergic system. For instance, emotional face processing is impaired by acute psilocybin administration, a serotonin (5-HT) 1A and 2A receptor agonist. However, the spatiotemporal brain mechanisms underlying these modulations are poorly understood. Here, we investigated the spatiotemporal brain dynamics underlying psilocybin-induced modulations during emotional face processing. Electrical neuroimaging analyses were applied to visual evoked potentials in response to emotional faces, following psilocybin and placebo administration. Our results indicate a first time period of strength (i.e., Global Field Power) modulation over the 168-189 ms poststimulus interval, induced by psilocybin. A second time period of strength modulation was identified over the 211-242 ms poststimulus interval. Source estimations over these 2 time periods further revealed decreased activity in response to both neutral and fearful faces within limbic areas, including amygdala and parahippocampal gyrus, and the right temporal cortex over the 168-189 ms interval, and reduced activity in response to happy faces within limbic and right temporo-occipital brain areas over the 211-242 ms interval. Our results indicate a selective and temporally dissociable effect of psilocybin on the neuronal correlates of emotional face processing, consistent with a modulation of the top-down control. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  4. Affinity column for purification of the human platelet thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptor

    International Nuclear Information System (INIS)

    Venton, D.L.; Arora, S.K.; Kim, S.O.; Lim, C.T.; Le Breton, G.C.

    1987-01-01

    The TXA 2 /PGH 2 receptor antagonist, 13-azaprostanoic acid (13-APA), was synthesized and used as the immobilized ligand in the affinity column purification of the 13-APA/U46619 binding component in human platelets. Diazo coupling of the ligand to the phenol of this tyr-gly-gly-NH-(CO)-O-Sepharose gave the affinity column material. Isolated platelet membranes were solubilized with detergent, applied directly to the affinity column and the eluate collected as 6 x 70 ml fractions. For each fraction, protein concentration and specific 3 H-13-APA/numberH-U46619 binding were determined. The majority of the applied protein (>98%) eluted in fraction number1. However, the specific 13-APA/U46619 binding per mg of protein was localized in fractions number4 and number5, representing approximately a 500-fold purification of this binding component. These results suggest that the platelet TXA 2 /PGH 2 receptor protein is retarded by this column, and that starting from crude, solubilized platelet membranes, a single pass through the column provides a 500-fold purification of the receptor

  5. Milrinone attenuates thromboxane receptor-mediated hyperresponsiveness in hypoxic pulmonary arterial myocytes.

    Science.gov (United States)

    Santhosh, K T; Elkhateeb, O; Nolette, N; Outbih, O; Halayko, A J; Dakshinamurti, S

    2011-07-01

    Neonatal pulmonary hypertension (PPHN) is characterized by pulmonary vasoconstriction, due in part to dysregulation of the thromboxane prostanoid (TP) receptor. Hypoxia induces TP receptor-mediated hyperresponsiveness, whereas serine phosphorylation mediates desensitization of TP receptors. We hypothesized that prostacyclin (IP) receptor activity induces TP receptor phosphorylation and decreases ligand affinity; that TP receptor sensitization in hypoxic myocytes is due to IP receptor inactivation; and that this would be reversible by the cAMP-specific phosphodiesterase inhibitor milrinone. We examined functional regulation of TP receptors by serine phosphorylation and effects of IP receptor stimulation and protein kinase A (PKA) activity on TP receptor sensitivity in myocytes from neonatal porcine resistance pulmonary arteries after 72 h hypoxia in vitro. Ca(2+) response curves to U46619 (TP receptor agonist) were determined in hypoxic and normoxic myocytes incubated with or without iloprost (IP receptor agonist), forskolin (adenylyl cyclase activator), H8 (PKA inhibitor) or milrinone. TP and IP receptor saturation binding kinetics were measured in presence of iloprost or 8-bromo-cAMP. Ligand affinity for TP receptors was normalized in vitro by IP receptor signalling intermediates. However, IP receptor affinity was compromised in hypoxic myocytes, decreasing cAMP production. Milrinone normalized TP receptor sensitivity in hypoxic myocytes by restoring PKA-mediated regulatory TP receptor phosphorylation. TP receptor sensitivity and EC(50) for TP receptor agonists was regulated by PKA, as TP receptor serine phosphorylation by PKA down-regulated Ca(2+) mobilization. Hypoxia decreased IP receptor activity and cAMP generation, inducing TP receptor hyperresponsiveness, which was reversed by milrinone. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  6. Prostaglandin E2 and thromboxane B2 release from human monocytes treated with bacterial lipopolysaccharide

    International Nuclear Information System (INIS)

    Nichols, F.C.; Garrison, S.W.; Davis, H.W.

    1988-01-01

    We investigated the capacity of counterflow-isolated human monocytes to independently synthesize thromboxane B2 (TxB2) and prostaglandin E2 (PGE2) when stimulated with bacterial lipopolysaccharide (LPS). Independent metabolism was confirmed by establishing different specific activities (dpm/ng) of TxB2 and PGE2 released from LPS-treated cells. For metabolites released during the initial 2-hr treatment period, the specific activity of PGE2 was approximately threefold higher than that of TxB2 regardless of labeling with [3H]arachidonic acid (AA) or [14C]AA. Cells that were pulse-labeled for 2 hr with [3H]AA demonstrated a decreasing PGE2 specific activity over 24 hr, whereas the TxB2 specific activity remained unchanged. In contrast, cells continuously exposed to [14C]AA demonstrated an increasing TxB2 specific activity that approached the level of PGE2 by 24 hr. These results suggest the presence of at least 2 cyclooxygenase metabolic compartments in counterflow-isolated monocytes. Although freshly isolated monocytes have been reported to contain variable numbers of adherent platelets, additional experiments demonstrated that counterflow-isolated platelets are not capable of releasing elevated levels of TxB2 or PGE2 when treated with LPS. It is proposed from these findings that at least two subsets of monocytes exist in peripheral blood that can be distinguished on the basis of independent conversion of AA to TxB2 and PGE2

  7. Examination of thromboxane synthase as a prognostic factor and therapeutic target in non-small cell lung cancer

    LENUS (Irish Health Repository)

    Cathcart, Mary-Clare

    2011-03-09

    Abstract Background Thromboxane synthase (TXS) metabolises prostaglandin H2 into thromboxanes, which are biologically active on cancer cells. TXS over-expression has been reported in a range of cancers, and associated with a poor prognosis. TXS inhibition induces cell death in-vitro, providing a rationale for therapeutic intervention. We aimed to determine the expression profile of TXS in NSCLC and if it is prognostic and\\/or a survival factor in the disease. Methods TXS expression was examined in human NSCLC and matched controls by western analysis and IHC. TXS metabolite (TXB2) levels were measured by EIA. A 204-patient NSCLC TMA was stained for COX-2 and downstream TXS expression. TXS tissue expression was correlated with clinical parameters, including overall survival. Cell proliferation\\/survival and invasion was examined in NSCLC cells following both selective TXS inhibition and stable TXS over-expression. Results TXS was over-expressed in human NSCLC samples, relative to matched normal controls. TXS and TXB2 levels were increased in protein (p < 0.05) and plasma (p < 0.01) NSCLC samples respectively. TXS tissue expression was higher in adenocarcinoma (p < 0.001) and female patients (p < 0.05). No significant correlation with patient survival was observed. Selective TXS inhibition significantly reduced tumour cell growth and increased apoptosis, while TXS over-expression stimulated cell proliferation and invasiveness, and was protective against apoptosis. Conclusion TXS is over-expressed in NSCLC, particularly in the adenocarcinoma subtype. Inhibition of this enzyme inhibits proliferation and induces apoptosis. Targeting thromboxane synthase alone, or in combination with conventional chemotherapy is a potential therapeutic strategy for NSCLC.

  8. The Alzheimer Disease Protective Mutation A2T Modulates Kinetic and Thermodynamic Properties of Amyloid-β (Aβ) Aggregation*

    Science.gov (United States)

    Benilova, Iryna; Gallardo, Rodrigo; Ungureanu, Andreea-Alexandra; Castillo Cano, Virginia; Snellinx, An; Ramakers, Meine; Bartic, Carmen; Rousseau, Frederic; Schymkowitz, Joost; De Strooper, Bart

    2014-01-01

    Missense mutations in alanine 673 of the amyloid precursor protein (APP), which corresponds to the second alanine of the amyloid β (Aβ) sequence, have dramatic impact on the risk for Alzheimer disease; A2V is causative, and A2T is protective. Assuming a crucial role of amyloid-Aβ in neurodegeneration, we hypothesized that both A2V and A2T mutations cause distinct changes in Aβ properties that may at least partially explain these completely different phenotypes. Using human APP-overexpressing primary neurons, we observed significantly decreased Aβ production in the A2T mutant along with an enhanced Aβ generation in the A2V mutant confirming earlier data from non-neuronal cell lines. More importantly, thioflavin T fluorescence assays revealed that the mutations, while having little effect on Aβ42 peptide aggregation, dramatically change the properties of the Aβ40 pool with A2V accelerating and A2T delaying aggregation of the Aβ peptides. In line with the kinetic data, Aβ A2T demonstrated an increase in the solubility at equilibrium, an effect that was also observed in all mixtures of the A2T mutant with the wild type Aβ40. We propose that in addition to the reduced β-secretase cleavage of APP, the impaired propensity to aggregate may be part of the protective effect conferred by A2T substitution. The interpretation of the protective effect of this mutation is thus much more complicated than proposed previously. PMID:25253695

  9. Irradiation of a 2.5 m long SciFi module with 24 GeV/c protons to the dose profile expected in LHCb

    CERN Document Server

    Rodrigues Cavalcante, Ana Barbara; Glaser, Maurice; Joram, Christian; Karacson, Matthias; Kristic, Robert; Ravotti, Federico; Riggaz, Nicolas

    2015-01-01

    A 2.5 m long and 13 cm wide SciFi module, made of a 6-layer single fibre mat, was irradiated with 24 GeV/c protons in the new CERN PS IRRAD facility. The module is equipped with an aluminised mylar mirror and was previously carefully characterised in a test beam experiment in the CERN H8 zone. For the irradiation the module was tilted by $7 ^o$ w.r.t. the beam axis. A translation table allowed to move the module during the irradiation transverse to the beam in order to generate the dose distribution expected in LHCb after an integrated luminosity of 50 fb$^{-1}$, including the very sharp rise at the mirror end to 35 kGy. The dose distribution was derived from the generation of sodium isotopes in the aluminium strips placed in front of and behind the module. The dosimetry relies mainly on the activity of the long-lived Na-22 isotope, as the short-lived Na-24 gave in our specific case less precise results. The irradiated zone corresponds to an approximately 25 mm wide band running along the fibre mat, at 32 mm ...

  10. Involvement of COX2–thromboxane pathway in TCDD-induced precardiac edema in developing zebrafish

    International Nuclear Information System (INIS)

    Teraoka, Hiroki; Okuno, Yuki; Nijoukubo, Daisuke; Yamakoshi, Ayumi; Peterson, Richard E.; Stegeman, John J.; Kitazawa, Takio; Hiraga, Takeo; Kubota, Akira

    2014-01-01

    Highlights: • We establish a new indicator of pericardial edema in developing zebrafish (precardiac edema). • Property of precardiac edema by TCDD is similar to that for conventional pericardial edema. • COX2b (but not COX2a)–thromboxane pathway is involved in precardiac edema by TCDD. - Abstract: The cardiovascular system is one of the most characteristic and important targets for developmental toxicity by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in fish larvae. However, knowledge of the mechanism of TCDD-induced edema after heterodimerization of aryl hydrocarbon receptor type 2 (AHR2) and AHR nuclear translocator type 1 (ARNT1) is still limited. In the present study, microscopic analysis with a high-speed camera revealed that TCDD increased the size of a small cavity between the heart and body wall in early eleutheroembryos, a toxic effect that we designate as precardiac edema. A concentration–response curve for precardiac edema at 2 days post fertilization (dpf) showed close similarity to that for conventional pericardial edema at 3 dpf. Precardiac edema caused by TCDD was reduced by morpholino knockdown of AHR2 and ARNT1, as well as by an antioxidant (ascorbic acid). A selective inhibitor of cyclooxygenase type 2 (COX2), NS398, also markedly inhibited TCDD-induced precardiac edema. A thromboxane receptor (TP) antagonist, ICI-192,605 almost abolished TCDD-induced precardiac edema and this effect was canceled by U46619, a TP agonist, which was not influential in the action of TCDD by itself. Knockdown of COX2b and thromboxane A synthase 1 (TBXS), but not COX2a, strongly reduced TCDD-induced precardiac edema. Knockdown of COX2b was without effect on mesencephalic circulation failure caused by TCDD. The edema by TCDD was also inhibited by knockdown of c-mpl, a thrombopoietin receptor necessary for thromobocyte production. Finally, induction of COX2b, but not COX2a, by TCDD was seen in eleutheroembryos at 3 dpf. These results suggest a role of the COX2b–thromboxane

  11. Involvement of COX2–thromboxane pathway in TCDD-induced precardiac edema in developing zebrafish

    Energy Technology Data Exchange (ETDEWEB)

    Teraoka, Hiroki, E-mail: hteraoka@rakuno.ac.jp [School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu (Japan); Okuno, Yuki; Nijoukubo, Daisuke; Yamakoshi, Ayumi [School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu (Japan); Peterson, Richard E. [School of Pharmacy, University of Wisconsin, Madison, WI (United States); Stegeman, John J. [Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA (United States); Kitazawa, Takio; Hiraga, Takeo [School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu (Japan); Kubota, Akira [School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu (Japan); Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA (United States)

    2014-09-15

    Highlights: • We establish a new indicator of pericardial edema in developing zebrafish (precardiac edema). • Property of precardiac edema by TCDD is similar to that for conventional pericardial edema. • COX2b (but not COX2a)–thromboxane pathway is involved in precardiac edema by TCDD. - Abstract: The cardiovascular system is one of the most characteristic and important targets for developmental toxicity by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in fish larvae. However, knowledge of the mechanism of TCDD-induced edema after heterodimerization of aryl hydrocarbon receptor type 2 (AHR2) and AHR nuclear translocator type 1 (ARNT1) is still limited. In the present study, microscopic analysis with a high-speed camera revealed that TCDD increased the size of a small cavity between the heart and body wall in early eleutheroembryos, a toxic effect that we designate as precardiac edema. A concentration–response curve for precardiac edema at 2 days post fertilization (dpf) showed close similarity to that for conventional pericardial edema at 3 dpf. Precardiac edema caused by TCDD was reduced by morpholino knockdown of AHR2 and ARNT1, as well as by an antioxidant (ascorbic acid). A selective inhibitor of cyclooxygenase type 2 (COX2), NS398, also markedly inhibited TCDD-induced precardiac edema. A thromboxane receptor (TP) antagonist, ICI-192,605 almost abolished TCDD-induced precardiac edema and this effect was canceled by U46619, a TP agonist, which was not influential in the action of TCDD by itself. Knockdown of COX2b and thromboxane A synthase 1 (TBXS), but not COX2a, strongly reduced TCDD-induced precardiac edema. Knockdown of COX2b was without effect on mesencephalic circulation failure caused by TCDD. The edema by TCDD was also inhibited by knockdown of c-mpl, a thrombopoietin receptor necessary for thromobocyte production. Finally, induction of COX2b, but not COX2a, by TCDD was seen in eleutheroembryos at 3 dpf. These results suggest a role of the COX2b–thromboxane

  12. Self-pulsing in a 2 km single-mode fiber with the seed source broadened via WNS phase modulation

    Science.gov (United States)

    Zha, Congwen; Sun, Yinhong; Wang, Yanshan; Li, Tenglong; Peng, Wanjing; Ma, Yi; Zhang, Kai

    2018-03-01

    The seed source with spectral linewidth broadening via phase modulation is potential to achieve the higher output power with effective SBS suppression. However, self-pulsing from the amplifier output is harmful. In this work, we study the self-pulsing characteristics in a long single-mode fiber with lower self-pulsing threshold instead of the high power amplifier. We provide a powerful experimental support for the self-pulsing mechanism in high-power narrow-linewidth fiber lasers, which is important for further output power scaling.

  13. A2A-D2 receptor-receptor interaction modulates gliotransmitter release from striatal astrocyte processes.

    Science.gov (United States)

    Cervetto, Chiara; Venturini, Arianna; Passalacqua, Mario; Guidolin, Diego; Genedani, Susanna; Fuxe, Kjell; Borroto-Esquela, Dasiel O; Cortelli, Pietro; Woods, Amina; Maura, Guido; Marcoli, Manuela; Agnati, Luigi F

    2017-01-01

    Evidence for striatal A2A-D2 heterodimers has led to a new perspective on molecular mechanisms involved in schizophrenia and Parkinson's disease. Despite the increasing recognition of astrocytes' participation in neuropsychiatric disease vulnerability, involvement of striatal astrocytes in A2A and D2 receptor signal transmission has never been explored. Here, we investigated the presence of D2 and A2A receptors in isolated astrocyte processes prepared from adult rat striatum by confocal imaging; the effects of receptor activation were measured on the 4-aminopyridine-evoked release of glutamate from the processes. Confocal analysis showed that A2A and D2 receptors were co-expressed on the same astrocyte processes. Evidence for A2A-D2 receptor-receptor interactions was obtained by measuring the release of the gliotransmitter glutamate: D2 receptors inhibited the glutamate release, while activation of A2A receptors, per se ineffective, abolished the effect of D2 receptor activation. The synthetic D2 peptide VLRRRRKRVN corresponding to the receptor region involved in electrostatic interaction underlying A2A-D2 heteromerization abolished the ability of the A2A receptor to antagonize the D2 receptor-mediated effect. Together, the findings are consistent with heteromerization of native striatal astrocytic A2A-D2 receptors that via allosteric receptor-receptor interactions could play a role in the control of striatal glutamatergic transmission. These new findings suggest possible new pathogenic mechanisms and/or therapeutic approaches to neuropsychiatric disorders. © 2016 International Society for Neurochemistry.

  14. MMP2-A2M interaction increases ECM accumulation in aged rat kidney and its modulation by calorie restriction

    Science.gov (United States)

    Kim, Kyung Mok; Chung, Ki Wung; Jeong, Hyeong Oh; Lee, Bonggi; Kim, Dae Hyun; Park, June Whoun; Kim, Seong Min; Yu, Byung Pal; Chung, Hae Young

    2018-01-01

    Age-associated renal fibrosis is related with renal function decline during aging. Imbalance between accumulation and degradation of extracellular matrix is key feature of fibrosis. In this study, RNA-sequencing (RNA-Seq) results based on next-generation sequencing (NGS) data were analyzed to identify key proteins that change during aging and calorie restriction (CR). Among the changed genes, A2M and MMP2, which are known to interact, exhibited the highest between centrality (BC) and degree values when analyzed by protein–protein interaction (PPI). Both mRNA and protein levels of MMP2 and A2M were increased during aging. Furthermore, the interaction between MMP2 and A2M was verified by immunoprecipitation and immunohistochemistry. MMP2 activity was further measured under the presence or absence of A2M-MMP2 interaction. MMP2 activity, which was increased under the absence of A2M-MMP2 interaction, was significantly decreased under the presence of interactions in aged kidney. We further hypothesized that the interaction between A2M-MMP2 played a role in the inactivation of MMP2 leading to accumulation of ECM including collagen type I and IV. Aged kidney showed highly accumulated MMP2 substrate proteins despite of increased MMP2 protein expression and CR blunted these accumulation. Additional in vivo analysis revealed that the signal transducer and activator of transcription (STAT) 3 transcriptional factor was significantly increased thus increasing A2M expression during aging. STAT3 activating cytokines were also highly increased in aged kidney. In conclusion, the results of the present study indicate that A2M-MMP2 interaction has a role in age-associated renal ECM accumulation and in the suppression such fibrosis by CR. PMID:29464020

  15. Adenosine A2A receptors modulate the dopamine D2 receptor-mediated inhibition of synaptic transmission in the mouse prefrontal cortex.

    Science.gov (United States)

    Real, Joana I; Simões, Ana Patrícia; Cunha, Rodrigo A; Ferreira, Samira G; Rial, Daniel

    2018-05-01

    Prefrontal cortex (PFC) circuits are modulated by dopamine acting on D 1 - and D 2 -like receptors, which are pharmacologically exploited to manage neuropsychiatric conditions. Adenosine A 2A receptors (A 2 A R) also control PFC-related responses and A 2 A R antagonists are potential anti-psychotic drugs. As tight antagonistic A 2 A R-D 2 R and synergistic A 2 A R-D 1 R interactions occur in other brain regions, we now investigated the crosstalk between A 2 A R and D 1 /D 2 R controlling synaptic transmission between layers II/III and V in mouse PFC coronal slices. Dopamine decreased synaptic transmission, a presynaptic effect based on the parallel increase in paired-pulse responses. Dopamine inhibition was prevented by the D 2 R-like antagonist sulpiride but not by the D 1 R antagonist SCH23390 and was mimicked by the D 2 R agonist sumanirole, but not by the agonists of either D 4 R (A-412997) or D 3 R (PD128907). Dopamine inhibition was prevented by the A 2 A R antagonist, SCH58261, and attenuated in A 2 A R knockout mice. Accordingly, triple-labelling immunocytochemistry experiments revealed the co-localization of A 2 A R and D 2 R immunoreactivity in glutamatergic (vGluT1-positive) nerve terminals of the PFC. This reported positive A 2 A R-D 2 R interaction controlling PFC synaptic transmission provides a mechanistic justification for the anti-psychotic potential of A 2 A R antagonists. © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  16. The neuronal Ca(2+) -binding protein 2 (NECAB2) interacts with the adenosine A(2A) receptor and modulates the cell surface expression and function of the receptor.

    Science.gov (United States)

    Canela, Laia; Luján, Rafael; Lluís, Carme; Burgueño, Javier; Mallol, Josefa; Canela, Enric I; Franco, Rafael; Ciruela, Francisco

    2007-09-01

    Heptaspanning membrane also known as G protein-coupled receptors (GPCR) do interact with a variety of intracellular proteins whose function is regulate receptor traffic and/or signaling. Using a yeast two-hybrid screen, NECAB2, a neuronal calcium binding protein, was identified as a binding partner for the adenosine A(2A) receptor (A(2A)R) interacting with its C-terminal domain. Co-localization, co-immunoprecipitation and pull-down experiments showed a close and specific interaction between A(2A)R and NECAB2 in both transfected HEK-293 cells and also in rat striatum. Immunoelectron microscopy detection of NECAB2 and A(2A)R in the rat striatopallidal structures indicated that both proteins are co-distributed in the same glutamatergic nerve terminals. The interaction of NECAB2 with A(2A)R modulated the cell surface expression, the ligand-dependent internalization and the receptor-mediated activation of the MAPK pathway. Overall, these results show that A(2A)R interacts with NECAB2 in striatal neurones co-expressing the two proteins and that the interaction is relevant for A(2A)R function.

  17. Enthalpy-Entropy Compensation in the Binding of Modulators at Ionotropic Glutamate Receptor GluA2

    DEFF Research Database (Denmark)

    Krintel, Christian; Francotte, Pierre; Pickering, Darryl S

    2016-01-01

    of 5 was examined with x-ray crystallography, showing that the only change compared to that of earlier compounds was the orientation of Ser-497 pointing toward the hydroxyl group of 5. The favorable enthalpy can be explained by the formation of a hydrogen bond from the side-chain hydroxyl group of Ser...... of modulators BPAM97 (2) and BPAM344 (3) into a hydroxyl group (BPAM557 (4) and BPAM521 (5), respectively), leads to a more favorable binding enthalpy (ΔH, kcal/mol) from −4.9 (2) and −7.5 (3) to −6.2 (4) and −14.5 (5), but also a less favorable binding entropy (−TΔS, kcal/mol) from −2.3 (2) and −1.3 (3) to −0......-497 to the hydroxyl group of 5, whereas the unfavorable entropy might be due to desolvation effects combined with a conformational restriction of Ser-497 and 5. In summary, this study shows a remarkable example of enthalpy-entropy compensation in drug development accompanied with a likely explanation...

  18. Modulation of mitochondrial function and morphology by interaction of Omi/HtrA2 with the mitochondrial fusion factor OPA1

    Energy Technology Data Exchange (ETDEWEB)

    Kieper, Nicole; Holmstroem, Kira M.; Ciceri, Dalila; Fiesel, Fabienne C. [Center of Neurology and Hertie Institute for Clinical Brain Research, 72076 Tuebingen (Germany); Wolburg, Hartwig [Institute of Pathology, University of Tuebingen, 72076 Tuebingen (Germany); Ziviani, Elena; Whitworth, Alexander J. [Medical Research Council Centre for Developmental and Biomedical Genetics, University of Sheffield, Sheffield S10 2TN (United Kingdom); Martins, L. Miguel [Cell Death Regulation Laboratory, MRC Toxicology Unit, Leicester LE1 9HN (United Kingdom); Kahle, Philipp J., E-mail: philipp.kahle@uni-tuebingen.de [Center of Neurology and Hertie Institute for Clinical Brain Research, 72076 Tuebingen (Germany); Krueger, Rejko, E-mail: rejko.krueger@uni-tuebingen.de [Center of Neurology and Hertie Institute for Clinical Brain Research, 72076 Tuebingen (Germany)

    2010-04-15

    Loss of Omi/HtrA2 function leads to nerve cell loss in mouse models and has been linked to neurodegeneration in Parkinson's and Huntington's disease. Omi/HtrA2 is a serine protease released as a pro-apoptotic factor from the mitochondrial intermembrane space into the cytosol. Under physiological conditions, Omi/HtrA2 is thought to be involved in protection against cellular stress, but the cytological and molecular mechanisms are not clear. Omi/HtrA2 deficiency caused an accumulation of reactive oxygen species and reduced mitochondrial membrane potential. In Omi/HtrA2 knockout mouse embryonic fibroblasts, as well as in Omi/HtrA2 silenced human HeLa cells and Drosophila S2R+ cells, we found elongated mitochondria by live cell imaging. Electron microscopy confirmed the mitochondrial morphology alterations and showed abnormal cristae structure. Examining the levels of proteins involved in mitochondrial fusion, we found a selective up-regulation of more soluble OPA1 protein. Complementation of knockout cells with wild-type Omi/HtrA2 but not with the protease mutant [S306A]Omi/HtrA2 reversed the mitochondrial elongation phenotype and OPA1 alterations. Finally, co-immunoprecipitation showed direct interaction of Omi/HtrA2 with endogenous OPA1. Thus, we show for the first time a direct effect of loss of Omi/HtrA2 on mitochondrial morphology and demonstrate a novel role of this mitochondrial serine protease in the modulation of OPA1. Our results underscore a critical role of impaired mitochondrial dynamics in neurodegenerative disorders.

  19. Modulation of mitochondrial function and morphology by interaction of Omi/HtrA2 with the mitochondrial fusion factor OPA1

    International Nuclear Information System (INIS)

    Kieper, Nicole; Holmstroem, Kira M.; Ciceri, Dalila; Fiesel, Fabienne C.; Wolburg, Hartwig; Ziviani, Elena; Whitworth, Alexander J.; Martins, L. Miguel; Kahle, Philipp J.; Krueger, Rejko

    2010-01-01

    Loss of Omi/HtrA2 function leads to nerve cell loss in mouse models and has been linked to neurodegeneration in Parkinson's and Huntington's disease. Omi/HtrA2 is a serine protease released as a pro-apoptotic factor from the mitochondrial intermembrane space into the cytosol. Under physiological conditions, Omi/HtrA2 is thought to be involved in protection against cellular stress, but the cytological and molecular mechanisms are not clear. Omi/HtrA2 deficiency caused an accumulation of reactive oxygen species and reduced mitochondrial membrane potential. In Omi/HtrA2 knockout mouse embryonic fibroblasts, as well as in Omi/HtrA2 silenced human HeLa cells and Drosophila S2R+ cells, we found elongated mitochondria by live cell imaging. Electron microscopy confirmed the mitochondrial morphology alterations and showed abnormal cristae structure. Examining the levels of proteins involved in mitochondrial fusion, we found a selective up-regulation of more soluble OPA1 protein. Complementation of knockout cells with wild-type Omi/HtrA2 but not with the protease mutant [S306A]Omi/HtrA2 reversed the mitochondrial elongation phenotype and OPA1 alterations. Finally, co-immunoprecipitation showed direct interaction of Omi/HtrA2 with endogenous OPA1. Thus, we show for the first time a direct effect of loss of Omi/HtrA2 on mitochondrial morphology and demonstrate a novel role of this mitochondrial serine protease in the modulation of OPA1. Our results underscore a critical role of impaired mitochondrial dynamics in neurodegenerative disorders.

  20. Radiation-induced changes in production of prostaglandins Fsub(2α), E, and thromboxane B2 in guinea pig parenchymal lung tissues

    International Nuclear Information System (INIS)

    Steel, L.K.; Catravas, G.N.

    1982-01-01

    At 1 hour to 4 days after unilateral exposure of guinea pigs to a single dose (0.5, 1.5, or 3.0 Gy) of gamma-radiation, changes were detected in prostaglandin and thromboxane concentrations in parenchymal lung tissues. At 1-3 hours after exposure, tissue levels of PGFsub(2α), PGE, and thromboxane B 2 were significantly elevated in animals receiving 3.0 Gy, with the magnitude of alteration revealing a radiation dose effect. By 24 hours, tissue prostaglandin and thromboxane levels returned to near control values. Lung tissue synthesis of prostaglandins in response to H-1 receptor stimulation by the exogenous addition of histamine revealed similar radiation dose effects. The carboxylic acid ionophore A23187, exogenously applied to lung tissues, revealed a transient peak of increased sensitivity to ionophore stimulation for TxB 2 synthesis at 24 hours and for PGFsub(2α) at 72 hours post-irradiation. The data suggest that significant alterations in prostaglandin and thromboxane concentrations in parenchymal lung tissues occur following irradiation, in a dose-dependent manner, and that altered responsiveness to H-1 receptor stimulation and divalent cation transport also occur

  1. Radiation-induced changes in production of prostaglandins Fsub(2. cap alpha. ), E, and thromboxane B/sub 2/ in guinea pig parenchymal lung tissues

    Energy Technology Data Exchange (ETDEWEB)

    Steel, L K; Catravas, G N [Armed Forces Radiobiology Research Inst., Bethesda, MD (USA)

    1982-11-01

    At 1 hour to 4 days after unilateral exposure of guinea pigs to a single dose (0.5, 1.5, or 3.0 Gy) of gamma-radiation, changes were detected in prostaglandin and thromboxane concentrations in parenchymal lung tissues. At 1-3 hours after exposure, tissue levels of PGFsub(2..cap alpha..), PGE, and thromboxane B/sub 2/ were significantly elevated in animals receiving 3.0 Gy, with the magnitude of alteration revealing a radiation dose effect. By 24 hours, tissue prostaglandin and thromboxane levels returned to near control values. Lung tissue synthesis of prostaglandins in response to H-1 receptor stimulation by the exogenous addition of histamine revealed similar radiation dose effects. The carboxylic acid ionophore A23187, exogenously applied to lung tissues, revealed a transient peak of increased sensitivity to ionophore stimulation for TxB/sub 2/ synthesis at 24 hours and for PGFsub(2..cap alpha..) at 72 hours post-irradiation. The data suggest that significant alterations in prostaglandin and thromboxane concentrations in parenchymal lung tissues occur following irradiation, in a dose-dependent manner, and that altered responsiveness to H-1 receptor stimulation and divalent cation transport also occur.

  2. 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...

  3. Expression of the TPα and TPβ isoforms of the thromboxane prostanoid receptor (TP) in prostate cancer: clinical significance and diagnostic potential.

    Science.gov (United States)

    Mulvaney, Eamon P; Shilling, Christine; Eivers, Sarah B; Perry, Antoinette S; Bjartell, Anders; Kay, Elaine W; Watson, R William; Kinsella, B Therese

    2016-11-08

    The prostanoid thromboxane (TX)A2 plays a central role in haemostasis and is increasingly implicated in cancer progression. TXA2 signals through two T Prostanoid receptor (TP) isoforms termed TPα and TPβ, with both encoded by the TBXA2R gene. Despite exhibiting several functional and regulatory differences, the role of the individual TP isoforms in neoplastic diseases is largely unknown.This study evaluated expression of the TPα and TPβ isoforms in tumour microarrays of the benign prostate and different pathological (Gleason) grades of prostate cancer (PCa). Expression of TPβ was significantly increased in PCa relative to benign tissue and strongly correlated with increasing Gleason grade. Furthermore, higher TPβ expression was associated with increased risk of biochemical recurrence (BCR) and significantly shorter disease-free survival time in patients post-surgery. While TPα was more variably expressed than TPβ in PCa, increased/high TPα expression within the tumour also trended toward increased BCR and shorter disease-free survival time. Comparative genomic CpG DNA methylation analysis revealed substantial differences in the extent of methylation of the promoter regions of the TBXA2R that specifically regulate expression of TPα and TPβ, respectively, both in benign prostate and in clinically-derived tissue representative of precursor lesions and progressive stages of PCa. Collectively, TPα and TPβ expression is differentially regulated both in the benign and tumourigenic prostate, and coincides with clinical pathology and altered CpG methylation of the TBXA2R gene. Analysis of TPβ, or a combination of TPα/TPβ, expression levels may have significant clinical potential as a diagnostic biomarker and predictor of PCa disease recurrence.

  4. PDE2A2 regulates mitochondria morphology and apoptotic cell death via local modulation of cAMP/PKA signalling.

    Science.gov (United States)

    Monterisi, Stefania; Lobo, Miguel J; Livie, Craig; Castle, John C; Weinberger, Michael; Baillie, George; Surdo, Nicoletta C; Musheshe, Nshunge; Stangherlin, Alessandra; Gottlieb, Eyal; Maizels, Rory; Bortolozzi, Mario; Micaroni, Massimo; Zaccolo, Manuela

    2017-05-02

    cAMP/PKA signalling is compartmentalised with tight spatial and temporal control of signal propagation underpinning specificity of response. The cAMP-degrading enzymes, phosphodiesterases (PDEs), localise to specific subcellular domains within which they control local cAMP levels and are key regulators of signal compartmentalisation. Several components of the cAMP/PKA cascade are located to different mitochondrial sub-compartments, suggesting the presence of multiple cAMP/PKA signalling domains within the organelle. The function and regulation of these domains remain largely unknown. Here, we describe a novel cAMP/PKA signalling domain localised at mitochondrial membranes and regulated by PDE2A2. Using pharmacological and genetic approaches combined with real-time FRET imaging and high resolution microscopy, we demonstrate that in rat cardiac myocytes and other cell types mitochondrial PDE2A2 regulates local cAMP levels and PKA-dependent phosphorylation of Drp1. We further demonstrate that inhibition of PDE2A, by enhancing the hormone-dependent cAMP response locally, affects mitochondria dynamics and protects from apoptotic cell death.

  5. EphA2 modulates radiosensitive of hepatocellular carcinoma cells via p38/mitogen-activated protein kinase-mediated signal pathways

    Directory of Open Access Journals (Sweden)

    Qiao Jin

    2015-10-01

    Full Text Available This experiment was conducted to investigate the role of EPH receptor A2 (EphA2 in the modulation of radiosensitivity of hepatic cellular cancer (HCC cells and to determine whether p38/mitogen-activated protein kinase (p38MAPK signaling mediated EphA2 function in this respect. The protein expressions of EphA2 and phosphorylated p38MAPK were tested in HCC and normal hepatic tissues. In HCC 97H cells, EphA2 was overexpressed and knocked out by transfection with EphA2 expression vector and EphA2-ShRNA, respectively, prior to cell exposure to low-dose irradiation. Significantly upregulated EphA2 and phosphorylated p38MAPK were observed in HCC tissues, compared with those in normal hepatic tissues. Low-dose irradiation (1 Gy only caused minor damage to HCC 97H cells, as assessed by alterations in cell viability, apoptosis rate, and cell healing capacity (p = 0.072, p = 0.078, and p = 0.069 respectively. However, EphA2 knock-out in HCC 97H cells induced significant reduction in cell viability and cell healing capacity after these cells were subjected to low-dose irradiation. Apoptosis rate underwent dramatic increase (p < 0.01. By contrast, EphA2 overexpression in HCC 97H cells reversed these effects and enhanced cell colony formation rate, thus displaying remarkable attenuation of radiosensitivity of HCC 97H cells. Further, SB203580, a specific inhibitor of p38MAPK, was added to HCC 97H cells over-expressing EphA2. The effect of EphA2 overexpression on the radiosensitivity of HCC 97H cells was abrogated. Thus, the present study indicates that EphA2 have the ability to negatively regulate the radiosensitivity of HCC 97H cells, which mainly depends on 38MAPK-mediated signal pathways.

  6. Alterations in prostacyclin and thromboxane formation by chronic cigarette smoke exposure: temporal relationships and whole smoke vs. gas phase

    Energy Technology Data Exchange (ETDEWEB)

    Lubawy, W.C.; Culpepper, B.T.; Valentovic, M.A.

    1986-04-01

    Chronic cigarette smoke exposure in vivo causes decreased conversion of (/sup 14/C)arachidonic acid (AA) to prostacyclin (PGI2) by isolated aortic tissue and increased conversion to thromboxane (TXA2) by isolated platelets from rats. Alterations in the PGI2/TXA2 balance may be part of the mechanism through which smoking increases the risk of cardiovascular disease. To study the influence of smoke exposure duration on this response, male rats were exposed daily to 10 puffs of freshly generated cigarette smoke. Animals were killed after 1, 4, 14, 28 and 57 days of smoke exposure and 3, 7, 14 and 28 days after cessation of the 57-day of smoke-exposure regimen. Elevated carboxyhemoglobin levels during the smoke-exposure sessions verified smoke (gas phase) inhalation. Statistically significant alterations in prostacyclin synthesis preceded those of thromboxane. A decrease of 20-25% (P less than 0.05) in PGI2 production from (/sup 14/C)AA in isolated aortic tissue was found beginning 28 days after smoke was initiated and quickly rebounded when smoke exposure was terminated. Increased production of TXA2 from (/sup 14/C)AA by isolated platelets became statistically significant (P less than 0.05) on the 57th day and returned to normal 7-14 days after cessation of smoke exposure. To determine the effect of gas phase constituents on the PGI2/TXA2 balance a second series of experiments divided male and female Sprague-Dawley rats into sham, whole smoke and gas phase groups. Gas phase was produced by passing whole smoke through a Cambridge filter to remove particulate matter. Per cent COHb averaged 1.4 for sham, 7.8 for whole smoke and 9.4 for gas phase groups.

  7. Modulation of the conductance of a 2,2′-bipyridine-functionalized peptidic ion channel by Ni2+

    Science.gov (United States)

    Pilz, Claudia S.

    2008-01-01

    An α-helical amphipathic peptide with the sequence H2N-(LSSLLSL)3-CONH2 was obtained by solid phase synthesis and a 2,2′-bipyridine was coupled to its N-terminus, which allows complexation of Ni2+. Complexation of the 2,2′-bipyridine residues was proven by UV/Vis spectroscopy. The peptide helices were inserted into lipid bilayers (nano black lipid membranes, nano-BLMs) that suspend the pores of porous alumina substrates with a pore diameter of 60 nm by applying a potential difference. From single channel recordings, we were able to distinguish four distinct conductance states, which we attribute to an increasing number of peptide helices participating in the conducting helix bundle. Addition of Ni2+ in micromolar concentrations altered the conductance behaviour of the formed ion channels in nano-BLMs considerably. The first two conductance states appear much more prominent demonstrating that the complexation of bipyridine by Ni2+ results in a considerable confinement of the observed multiple conductance states. However, the conductance levels were independent of the presence of Ni2+. Moreover, from a detailed analysis of the open lifetimes of the channels, we conclude that the complexation of Ni2+ diminishes the frequency of channel events with larger open times. Electronic supplementary material The online version of this article (doi:10.1007/s00249-008-0298-8) contains supplementary material, which is available to authorized users. PMID:18347789

  8. An Lmx1b-miR135a2 regulatory circuit modulates Wnt1/Wnt signaling and determines the size of the midbrain dopaminergic progenitor pool.

    Directory of Open Access Journals (Sweden)

    Angela Anderegg

    Full Text Available MicroRNAs regulate gene expression in diverse physiological scenarios. Their role in the control of morphogen related signaling pathways has been less studied, particularly in the context of embryonic Central Nervous System (CNS development. Here, we uncover a role for microRNAs in limiting the spatiotemporal range of morphogen expression and function. Wnt1 is a key morphogen in the embryonic midbrain, and directs proliferation, survival, patterning and neurogenesis. We reveal an autoregulatory negative feedback loop between the transcription factor Lmx1b and a newly characterized microRNA, miR135a2, which modulates the extent of Wnt1/Wnt signaling and the size of the dopamine progenitor domain. Conditional gain of function studies reveal that Lmx1b promotes Wnt1/Wnt signaling, and thereby increases midbrain size and dopamine progenitor allocation. Conditional removal of Lmx1b has the opposite effect, in that expansion of the dopamine progenitor domain is severely compromised. Next, we provide evidence that microRNAs are involved in restricting dopamine progenitor allocation. Conditional loss of Dicer1 in embryonic stem cells (ESCs results in expanded Lmx1a/b+ progenitors. In contrast, forced elevation of miR135a2 during an early window in vivo phenocopies the Lmx1b conditional knockout. When En1::Cre, but not Shh::Cre or Nes::Cre, is used for recombination, the expansion of Lmx1a/b+ progenitors is selectively reduced. Bioinformatics and luciferase assay data suggests that miR135a2 targets Lmx1b and many genes in the Wnt signaling pathway, including Ccnd1, Gsk3b, and Tcf7l2. Consistent with this, we demonstrate that this mutant displays reductions in the size of the Lmx1b/Wnt1 domain and range of canonical Wnt signaling. We posit that microRNA modulation of the Lmx1b/Wnt axis in the early midbrain/isthmus could determine midbrain size and allocation of dopamine progenitors. Since canonical Wnt activity has recently been recognized as a key

  9. Increased cyclooxygenase-2 and thromboxane synthase expression is implicated in diosgenin-induced megakaryocytic differentiation in human erythroleukemia cells.

    Science.gov (United States)

    Cailleteau, C; Liagre, B; Battu, S; Jayat-Vignoles, C; Beneytout, J L

    2008-09-01

    Differentiation induction as a therapeutic strategy has, so far, the greatest impact in hematopoietic malignancies, most notably leukemia. Diosgenin is a very interesting natural product because, depending on the specific dose used, its biological effect is very different in HEL (human erythroleukemia) cells. For example, at 10 microM, diosgenin induced megakaryocytic differentiation, in contrast to 40 microM diosgenin, which induced apoptosis in HEL cells previously demonstrated using sedimentation field-flow fractionation (SdFFF). The goal of this work focused on the correlation between cyclooxygenase-2 (COX-2) and thromboxane synthase (TxS) and megakaryocytic differentiation induced by diosgenin in HEL cells. Furthermore, the technique of SdFFF, having been validated in our models, was used in this new study as an analytical tool that provided us with more or less enriched differentiated cell fractions that could then be used for further analyses of enzyme protein expression and activity for the first time. In our study, we showed the implication of COX-2 and TxS in diosgenin-induced megakaryocytic differentiation in HEL cells. Furthermore, we showed that the analytical technique of SdFFF may be used as a tool to confirm our results as a function of the degree of cell differentiation.

  10. Blood rheology of angina pectoris patients with myocardial injury after ischemia reperfusion and its effect on thromboxane B2 levels.

    Science.gov (United States)

    Wang, Wenlong; Huang, Xiaohui; Sun, Yiyong; Zhang, Jinying

    2018-01-01

    This study investigated the changes in the blood rheology of patients with angina pectoris and ischemia reperfusion injury and their effect on thromboxane B 2 (TXB 2 ) levels to examine their relationship. Forty patients with unstable angina pectoris who underwent elective percutaneous coronary intervention (PCI) were selected for the unstable angina group (UA group) and forty patients deemed free of coronary heart disease by coronary angiography were selected for the control group. Venous blood samples were drawn from all participants; patients in the UA group had blood drawn 1 day before and 1 day after the PCI procedure. Blood samples were used to analyze blood rheology and examine hemodynamic parameters, at the same time radioimmunoassay was applied to measure the concentrations of serum endothelin-1 (ET-1) and TXB 2 , and an automatic biochemical analyzer was used to detect the content of superoxide dismutase (SOD) and malondialdehyde (MDA). Our results showed the patients in the UA group all presented hyperviscosity; however the levels were higher for the patients in the UA group (after surgery) than for those in the UA group (before surgery). Patients in the control group exhibited normal levels, and the differences among groups were significant in pairwise comparisons (Pangina pectoris and ischemia reperfusion injury. The higher than normal TXB 2 levels can be used as a marker of platelet activation and a reference for clinical risk stratification, thus having great significance for the prevention and treatment of ischemia reperfusion injury and assessment of disease progression.

  11. Serum thromboxane B2 (TXB2 Determination is Influenced by Sample Incubation Temperature in Healthy Beagle Dogs

    Directory of Open Access Journals (Sweden)

    Aleš Jerin

    2009-01-01

    Full Text Available The measurement of serum thromboxane B2 (TXB2 production by platelets is a specific test for assessment of platelet cyclooxygenase (COX-1 activity following administration of non-steroidal anti-inflammatory drugs (NSAIDs. The aim of this study was to investigate the influence of sample incubation at 37 °C for one hour on serum TXB2 concentration in comparison with incubation at room temperature. A total of 54 blood samples for serum TXB2 measurements were collected from six healthy beagle dogs into two separate serum tubes. While one group of tubes was incubated in a 37 °C water bath, the second group of tubes was left to coagulate at room temperature, both for one hour. Serum TXB2 concentrations were measured by ELISA. The mean concentration (± SD of serum TXB2 in the group of samples that were incubated at 37 °C was significantly (P 2 concentration in healthy beagle dogs and demonstrate that validated methods for assessment of COX-1 activity by measurement of serum TXB2 should be used in order to make results more reliable and comparable between different studies. The results of this study might be of great help in planning NSAID studies in dogs by providing the information that TXB2 generation by platelets is influenced profoundly by incubation temperature.

  12. Continuous, automated manufacturing of string ribbon Si PV modules. PVMaT Phase 5A2 Subcontract: First Annual Report, 21 May 1998--20 May 1999

    Energy Technology Data Exchange (ETDEWEB)

    Hanoka, J.I.

    1999-11-03

    This report describes the first year of a 3-year PVMaT Phase 5A2 program. Evergreen Solar will soon be expanding into a multi-megawatt facility and the PVMaT work will be used to further the objective of a high-throughput automated production line in every aspect of PV module making from producing silicon ribbon to making a finished module. The project has four task areas for this first year: crystal growth; cell manufacturing; modules; and factory layout and automation. The vast majority of the work this first year has been in the crystal growth and cell manufacturing areas. Evergreen Solar has its own unique technology in each of these areas. In crystal growth, a key goal of this PVMaT project has been developing and deploying an improved string material. The high-temperature string materials are used to stabilize the edges of the growing silicon ribbon in the String Ribbon silicon sheet growth. The result has been one of the major successes of this first year. Significant cost reductions and yield improvements have emerged from this improved string material. In addition, some of the groundwork for automation of the String Ribbon crystal growth process has been laid and shows much promise. A method for controlling the edge meniscus height was developed, and a patent has been filed based on this discovery. In the cell manufacturing area, the focus has been on reducing the number of processing steps and on design and construction of high-speed processing equipment. The possibility of eliminating all pre-diffusion etching and going directly from growth to diffusion has been demonstrated on an R and D scale. Unique designs for high-speed drying equipment and for a high-speed contact and AR-coating application machine have been developed. In the latter case, the basic concepts underlying various aspects of the machine design have been successfully tested for viability. The integration of the different components of this machine into a smoothly working whole is now

  13. SU-E-P-35: Real-Time Patient Transit Dose Verification of Volumetric Modulated Arc Radiotherapy by a 2D Ionization Chamber Array

    Energy Technology Data Exchange (ETDEWEB)

    Liu, X

    2015-06-15

    Purpose: To explore the real-time dose verification method in volumetric modulated arc radiotherapy (VMAT) with a 2D array ion chamber array. Methods: The 2D ion chamber array was fixed on the panel of electronic portal imaging device (EPID). Source-detector distance (SDD)was 140cm. 8mm RW3 solid water was added to the detector panel to achieve maximum readings.The patient plans for esophageal, prostate and liver cancers were selected to deliver on the cylindrical Cheese phantom 5 times in order to validate the reproducibility of doses. Real-time patient transit dose measurements were performed at each fraction. Dose distributions wereevaluated using gamma index criteria of 3mm DTA and 3% dose difference referred to the firsttime Result. Results: The gamma index pass rate in the Cheese phantom were about 98%; The gamma index pass rate for esophageal, liver and prostate cancer patient were about 92%,94%, and 92%, respectively; Gamma pass rate for all single fraction were more than 90%. Conclusion: The 2D array is capable of monitoring the real time transit doses during VMAT delivery. It is helpful to improve the treatment accuracy.

  14. Bee venom phospholipase A2 protects against acetaminophen-induced acute liver injury by modulating regulatory T cells and IL-10 in mice.

    Directory of Open Access Journals (Sweden)

    Hyunseong Kim

    Full Text Available The aim of this study was to investigate the protective effects of phospholipase A2 (PLA2 from bee venom against acetaminophen-induced hepatotoxicity through CD4+CD25+Foxp3+ T cells (Treg in mice. Acetaminophen (APAP is a widely used antipyretic and analgesic, but an acute or cumulative overdose of acetaminophen can cause severe hepatic failure. Tregs have been reported to possess protective effects in various liver diseases and kidney toxicity. We previously found that bee venom strongly increased the Treg population in splenocytes and subsequently suppressed immune disorders. More recently, we found that the effective component of bee venom is PLA2. Thus, we hypothesized that PLA2 could protect against liver injury induced by acetaminophen. To evaluate the hepatoprotective effects of PLA2, C57BL/6 mice or interleukin-10-deficient (IL-10-/- mice were injected with PLA2 once a day for five days and sacrificed 24 h (h after acetaminophen injection. The blood sera were collected 0, 6, and 24 h after acetaminophen injection for the analysis of aspartate aminotransferase (AST and alanine aminotransferase (ALT. PLA2-injected mice showed reduced levels of serum AST, ALT, proinflammatory cytokines, and nitric oxide (NO compared with the PBS-injected control mice. However, IL-10 was significantly increased in the PLA2-injected mice. These hepatic protective effects were abolished in Treg-depleted mice by antibody treatment and in IL-10-/- mice. Based on these findings, it can be concluded that the protective effects of PLA2 against acetaminophen-induced hepatotoxicity can be mediated by modulating the Treg and IL-10 production.

  15. Bee venom phospholipase A2 protects against acetaminophen-induced acute liver injury by modulating regulatory T cells and IL-10 in mice.

    Science.gov (United States)

    Kim, Hyunseong; Keum, Dong June; Kwak, Jung won; Chung, Hwan-Suck; Bae, Hyunsu

    2014-01-01

    The aim of this study was to investigate the protective effects of phospholipase A2 (PLA2) from bee venom against acetaminophen-induced hepatotoxicity through CD4+CD25+Foxp3+ T cells (Treg) in mice. Acetaminophen (APAP) is a widely used antipyretic and analgesic, but an acute or cumulative overdose of acetaminophen can cause severe hepatic failure. Tregs have been reported to possess protective effects in various liver diseases and kidney toxicity. We previously found that bee venom strongly increased the Treg population in splenocytes and subsequently suppressed immune disorders. More recently, we found that the effective component of bee venom is PLA2. Thus, we hypothesized that PLA2 could protect against liver injury induced by acetaminophen. To evaluate the hepatoprotective effects of PLA2, C57BL/6 mice or interleukin-10-deficient (IL-10-/-) mice were injected with PLA2 once a day for five days and sacrificed 24 h (h) after acetaminophen injection. The blood sera were collected 0, 6, and 24 h after acetaminophen injection for the analysis of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). PLA2-injected mice showed reduced levels of serum AST, ALT, proinflammatory cytokines, and nitric oxide (NO) compared with the PBS-injected control mice. However, IL-10 was significantly increased in the PLA2-injected mice. These hepatic protective effects were abolished in Treg-depleted mice by antibody treatment and in IL-10-/- mice. Based on these findings, it can be concluded that the protective effects of PLA2 against acetaminophen-induced hepatotoxicity can be mediated by modulating the Treg and IL-10 production.

  16. Hydroxychavicol, a novel betel leaf component, inhibits platelet aggregation by suppression of cyclooxygenase, thromboxane production and calcium mobilization.

    Science.gov (United States)

    Chang, M C; Uang, B J; Tsai, C Y; Wu, H L; Lin, B R; Lee, C S; Chen, Y J; Chang, C H; Tsai, Y L; Kao, C J; Jeng, J H

    2007-09-01

    Platelet hyperactivity is important in the pathogenesis of cardiovascular diseases. Betel leaf (PBL) is consumed by 200-600 million betel quid chewers in the world. Hydroxychavicol (HC), a betel leaf component, was tested for its antiplatelet effect. We tested the effect of HC on platelet aggregation, thromboxane B(2) (TXB(2)) and reactive oxygen species (ROS) production, cyclooxygenase (COX) activity, ex vivo platelet aggregation and mouse bleeding time and platelet plug formation in vivo. The pharmacokinetics of HC in rats was also assessed. HC inhibited arachidonic acid (AA) and collagen-induced platelet aggregation and TXB(2) production. HC inhibited the thrombin-induced TXB(2) production, but not platelet aggregation. SQ29548, suppressed collagen- and thrombin-induced TXB(2) production, but not thrombin-induced platelet aggregation. HC also suppressed COX-1/COX-2 enzyme activity and the AA-induced ROS production and Ca(2+) mobilization. HC further inhibited the ex vivo platelet aggregation of platelet-rich plasma (>100 nmole/mouse) and prolonged platelet plug formation (>300 nmole/mouse) in mesenteric microvessels, but showed little effect on bleeding time in mouse tail. Moreover, pharmacokinetics analysis found that more than 99% of HC was metabolized within 3 min of administration in Sprague-Dawley rats in vivo. HC is a potent COX-1/COX-2 inhibitor, ROS scavenger and inhibits platelet calcium signaling, TXB(2) production and aggregation. HC could be a potential therapeutic agent for prevention and treatment of atherosclerosis and other cardiovascular diseases through its anti-inflammatory and antiplatelet effects, without effects on haemostatic functions.

  17. Measurement of urinary 11-dehydro-thromboxane B2 excretion in dogs with gastric dilatation-volvulus.

    Science.gov (United States)

    Baltzer, Wendy I; McMichael, Maureen A; Ruaux, Craig G; Noaker, Laura; Steiner, Jörg M; Williams, David A

    2006-01-01

    To measure 11-dehydro-thromboxane B2 (11-dTXB2) in urine of healthy control dogs, dogs undergoing ovariohysterectomy, and dogs with gastric dilatation-volvulus (GDV) and assess the relationship between urinary 11-dTXB2 concentrations in dogs with GDV and postoperative outcomes. Urine samples from 15 nonsurgical control dogs, 12 surgical control dogs, and 32 dogs with GVD. Urine samples were obtained from healthy pet dogs (ie, nonsurgical control dogs), dogs undergoing ovariohysterectomy at anesthetic induction and 1 hour following surgery (ie, surgical control dogs), and dogs with GDV at hospital admission and 1 hour following surgical derotation of the stomach (ie, GDV dogs). Urinary 11-dTXB2 concentrations were determined with an ELISA and normalized to urinary creatinine (Cr) concentrations by calculation of the 11-dTXB2 -to-Cr ratio. Differences in median 11-dTXB2 -to-Cr ratios among dogs and before and after surgery were analyzed. Urinary 11-dTXB2-to-Cr ratios did not differ between nonsurgical control dogs and surgical control dogs before or after surgery. Urinary 11-dTXB2-to-Cr ratios were significantly higher in GDV dogs at the time of hospital admission and 1 hour after surgery, compared with those of nonsurgical control dogs. Postoperative urine samples from GDV dogs had significantly higher 11-dTXB2-to-Cr ratios than postoperative urine samples from surgical control dogs. Median urinary 11-dTXB2-to-Cr ratios increased significantly in GDV dogs that developed postoperative complications. Urinary 11-dTXB2 concentration is increased in GDV dogs at the time of hospital admission and after surgical derotation of the stomach, compared with that of healthy dogs. An increased urinary 11-dTXB2-to-Cr ratio following surgery is associated with an increased incidence of postoperative complications in dogs with GDV.

  18. Endothelium depen dent factors of vasoconstriction (thromboxane B2 and vasodilation (6-prostaglandin F1α in children with primary arterial hype rten sion

    Directory of Open Access Journals (Sweden)

    Yu riy V. Marushko

    2015-09-01

    Full Text Available Background: Vasoconstrictor and vasodilator substances imbalance play a major role in the formation of arterial hypertension. But the ratio between thromboxane B2 and 6-prostaglandin F1α in children with various forms of primary arterial hypertension (PAH are insufficiently studied. Aim of the study: to explore the features of the content of thromboxane B2, 6-keto-PGF-1alfa and their correlation in children with different clinical and pathogenetic forms of PAH. Material and methods: The study involved 83 children aged 9 to 17 years. The first group included 32 children with stable PAH, the second – 32 children with labile PAH, the third (control group – 21 children with normal blood pressure. TXB2 and 6-PGF1α serum levels were investigated by ELISA. All children were held ambulatory blood pressure monitoring (ABPM. Results: Average TXB2 levels in boys were 25,05 ±6,43 ng/ml at stable PAH and 27,26 ±11,26 ng/ml at labile PAH, which exceeded their levels in the control group (p < 0,05. Girls’ TXB2 level was elevated at labile PAH (to 11,06 ±1,79 ng/ml, p < 0,05 and did not differ from the control group at stable PAH. Girls’ 6-PGF1α level was up to 3,41 ±0,52 ng/ml at stable PAH and up to 2,63 ±0,25 ng/ml at labile PAH. Conclusions: Violation of the ratio between endothelial vasoconstriction (thromboxane and vasodilatation (prostacyclin factors in boys with PAH is due to increased TXB2 levels compared with children with normal blood pressure (p < 0,05. Girls with PAH have better compensatory vasodilation opportunities compared with boys according to increased prostacyclin production. That prevents the progression of endothelial dysfunction and PAH stabilization in girls.

  19. Role of the cyclooxygenase 2-thromboxane pathway in 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced decrease in mesencephalic vein blood flow in the zebrafish embryo

    International Nuclear Information System (INIS)

    Teraoka, Hiroki; Kubota, Akira; Dong, Wu; Kawai, Yusuke; Yamazaki, Koji; Mori, Chisato; Harada, Yoshiteru; Peterson, Richard E.; Hiraga, Takeo

    2009-01-01

    Previously, we reported that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) evoked developmental toxicity required activation of aryl hydrocarbon receptor type 2 (AHR2), using zebrafish embryos. However, the downstream molecular targets of AHR2 activation are largely unknown and are the focus of the present investigation. TCDD induces cyclooxygenase 2 (COX2), a rate-limiting enzyme for prostaglandin synthesis in certain cells. In the present study, we investigated the role of the COX2-thromboxane pathway in causing a specific endpoint of TCDD developmental toxicity in the zebrafish embryo, namely, a decrease in regional blood flow in the dorsal midbrain. It was found that the TCDD-induced reduction in mesencephalic vein blood flow was markedly inhibited by selective COX2 inhibitors, NS-398 and SC-236, and by a general COX inhibitor, indomethacin, but not by a selective COX1 inhibitor, SC-560. Gene knock-down of COX2 by two different types of morpholino antisense oligonucleotides, but not by their negative homologs, also protected the zebrafish embryos from mesencephalic vein circulation failure caused by TCDD. This inhibitory effect of TCDD on regional blood flow in the dorsal midbrain was also blocked by selective antagonists of the thromboxane receptor (TP). Treatment of control zebrafish embryos with a TP agonist also caused a reduction in mesencephalic vein blood flow and it too was blocked by a TP antagonist, without any effect on trunk circulation. Finally, gene knock-down of thromboxane A synthase 1 (TBXS) with morpholinos but not by the morpholinos' negative homologs provided significant protection against TCDD-induced mesencephalic circulation failure. Taken together, these results point to a role of the prostanoid synthesis pathway via COX2-TBXS-TP in the local circulation failure induced by TCDD in the dorsal midbrain of the zebrafish embryo

  20. Dietary fish oil alters the lysophospholipid metabolomic profile and decreases urinary 11-dehydro thromboxane B₂ concentration in healthy Beagles.

    Science.gov (United States)

    Hall, Jean A; Brockman, Jeffrey A; Jewell, Dennis E

    2011-12-15

    Increased concentrations of dietary fish oil and antioxidants have been shown previously to change circulating concentrations of individual fatty acids (FAs) and vitamin E. The purpose of this study was to further investigate the effects of vitamins E and C, in combination with dietary fish oil, on selected blood and urinary biomarkers. Fifty adult Beagle dogs (mean age 5.3 years, range 1.4-14.2 years) were randomized into five dietary treatment groups for 90 days. All foods were complete and balanced and met the nutrient profiles of AAFCO for adult dogs. For 60 days before study initiation, dogs consumed a pretrial food that contained 74 IU/kg vitaminE and 0mg/kg vitaminC. The five experimental foods were confirmed by analytical methods to contain ≥ 640 IU/kg vitaminE and 130 mg/kg vitaminC (as fed). Experimental foods ranged from low levels of EPA and DHA (pretrial food and lowest experimental food had 0.01% EPA and no detectable DHA) to the highest experimental food with 0.25% EPA and 0.17% DHA. Serum was analyzed for FAs, vitamin E, and cholesterol concentrations; urine was analyzed for 11-dehydro thromboxane B(2) (TXB(2)). Serum was also used for metabolomic analysis. FA intake ranged from 0.02 g/day EPA and 0.02 g/day DHA to 0.58 g/day EPA and 0.39 g/day DHA. Increasing dietary concentrations of EPA and DHA resulted in increased serum concentrations of EPA and DHA in a dose-dependent fashion. Greater dietary vitamin E intake resulted in increased serum vitamin E concentrations (Pvitamin E concentrations (Pvitamin E concentration is enhanced primarily by feeding vitamin E and secondarily by serum cholesterol concentration. When feeding diets enriched with fish oil, the major negative predictor of urinary 11-dehydro TXB(2) concentration is serum EPA concentration. Plasma lysophospholipids can be dynamically regulated by dietary fish oil supplementation. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. Model-based analysis of thromboxane B2 and prostaglandin E2 as biomarkers in the safety evaluation of naproxen

    International Nuclear Information System (INIS)

    Sahota, Tarjinder; Sanderson, Ian; Danhof, Meindert; Della Pasqua, Oscar

    2014-01-01

    The assessment of safety in traditional toxicology protocols relies on evidence arising from observed adverse events (AEs) in animals and on establishing their correlation with different measures of drug exposure (e.g., C max and AUC). Such correlations, however, ignore the role of biomarkers, which can provide further insight into the underlying pharmacological mechanisms. Here we use naproxen as a paradigm drug to explore the feasibility of a biomarker-guided approach for the prediction of AEs in humans. A standard toxicology protocol was set up for the evaluation of effects of naproxen in rat, in which four doses were tested (7.5, 15, 40 and 80 mg/kg). In addition to sparse blood sampling for the assessment of exposure, thromboxane B 2 and prostaglandin E 2 were also collected in satellite groups. Nonlinear mixed effects modelling was used to evaluate the predictive performance of the approach. A one-compartmental model with first order absorption was found to best describe the pharmacokinetics of naproxen. A nonlinear relationship between dose and bioavailability was observed which leads to a less than proportional increase in naproxen concentrations with increasing doses. The pharmacodynamics of TXB 2 and PGE 2 was described by direct inhibition models with maximum pharmacological effects achieved at doses > 7.5 mg/kg. The predicted PKPD relationship in humans was within 10-fold of the values previously published. Moreover, our results indicate that biomarkers can be used to assess interspecies differences in PKPD and extrapolated data from animals to humans. Biomarker sampling should be used systematically in general toxicity studies. - Highlights: • Prediction of a drug's safety profile from preclinical protocols remains challenging. • Pharmacokinetic measures of safe exposure (e.g., AUC) ignore the role of biomarkers. • PKPD relationships enable the evaluation of adverse events in a mechanistic manner. • Major differences exist between rats and

  2. Thromboxane A{sub 2} receptor signaling promotes liver tissue repair after toxic injury through the enhancement of macrophage recruitment

    Energy Technology Data Exchange (ETDEWEB)

    Minamino, Tsutomu [Departments of Pharmacology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Departments of Gastroenterology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Ito, Yoshiya [Departments of Surgery, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Ohkubo, Hirotoki [Departments of Pharmacology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Departments of Surgery, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Hosono, Kanako; Suzuki, Tatsunori [Departments of Pharmacology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Sato, Takehito [Departments of Pharmacology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Departments of Gastroenterology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Ae, Takako; Shibuya, Akitaka [Departments of Gastroenterology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Sakagami, Hiroyuki [Departments of Anatomy, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Narumiya, Shuh [Department of Pharmacology, Kyoto University School of Medicine, Kyoto, 606-8315 (Japan); Koizumi, Wasaburo [Departments of Gastroenterology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Majima, Masataka, E-mail: mmajima@med.kitasato-u.ac.jp [Departments of Pharmacology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan)

    2012-02-15

    It is thought that thromboxane A{sub 2} (TxA{sub 2}) contributes to the progression of inflammation during acute hepatic injury; however, it is still unknown whether TxA{sub 2} is involved in liver repair. The objective of the present study was to examine the role of TxA{sub 2} receptor (TP) signaling in liver injury and repair in response to toxic injury. Carbon tetrachloride (CCl{sub 4}) was used to induce liver injury in TP knockout (TP{sup −/−}) mice and wild-type (WT) mice. In WT mice, serum levels of alanine aminotransferase (ALT) and the size of the necrotic area peaked at 24 and 48 h, respectively, and then declined. In TP{sup −/−} mice, the changes in ALT levels were similar to WT mice, but liver regeneration was impaired as evidenced by remained elevated levels of hepatic necrosis and by delayed hepatocyte proliferation, which was associated with the reduced expression of growth factors including interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα), and hepatocyte growth factor (HGF). In TP{sup −/−} mice, the accumulation of hepatic CD11b{sup +}/F4/80{sup +} macrophages in injured livers was attenuated, and the hepatic expression of monocyte chemoattractant protein-1 (MCP-1/CCL2) and its receptor, the C―C chemokine receptor (CCR2), was reduced compared to WT. Additionally, the application of the TP receptor agonist, U-46619, enhanced the expression of MCP-1/CCL2 and CCR2 in peritoneal macrophages, which was associated with increased levels of IL-6, TNFα and HGF. These results suggested that TP receptor signaling facilitates liver recovery following CCl{sub 4}-induced hepatotoxicity by affecting the expression of hepatotrophic growth factors, and through the recruitment of macrophages mediated by MCP-1/CCL2-CCR2 expression. -- Highlights: ► TP enhances liver regeneration by CCl{sub 4}. ► TP accumulates macrophages. ► TP up-regulates MCP-1.

  3. Patients with advanced periodontal disease before intensity-modulated radiation therapy are prone to develop bone healing problems : a 2-year prospective follow-up study

    NARCIS (Netherlands)

    Schuurhuis, Jennifer M; Stokman, Monique A; Witjes, Max J H; Reintsema, Harry; Langendijk, Johannes A; Vissink, Arjan; Spijkervet, Frederik K L

    PURPOSE: Intensity-modulated radiation therapy (IMRT) has changed radiation treatment of head and neck cancer (HNC). However, it is still unclear if and how IMRT changes oral morbidity outcomes. In this prospective study, we assessed the outcome of reducing post-IMRT sequelae by means of

  4. Salivary Thromboxane A2-Binding Proteins from Triatomine Vectors of Chagas Disease Inhibit Platelet-Mediated Neutrophil Extracellular Traps (NETs Formation and Arterial Thrombosis.

    Directory of Open Access Journals (Sweden)

    Daniella M Mizurini

    Full Text Available The saliva of blood-feeding arthropods contains a notable diversity of molecules that target the hemostatic and immune systems of the host. Dipetalodipin and triplatin are triatomine salivary proteins that exhibit high affinity binding to prostanoids, such as TXA2, thus resulting in potent inhibitory effect on platelet aggregation in vitro. It was recently demonstrated that platelet-derived TXA2 mediates the formation of neutrophil extracellular traps (NETs, a newly recognized link between inflammation and thrombosis that promote thrombus growth and stability.This study evaluated the ability of dipetalodipin and triplatin to block NETs formation in vitro. We also investigated the in vivo antithrombotic activity of TXA2 binding proteins by employing two murine models of experimental thrombosis. Remarkably, we observed that both inhibitors abolished the platelet-mediated formation of NETs in vitro. Dipetalodipin and triplatin significantly increased carotid artery occlusion time in a FeCl3-induced injury model. Treatment with TXA2-binding proteins also protected mice from lethal pulmonary thromboembolism evoked by the intravenous injection of collagen and epinephrine. Effective antithrombotic doses of dipetalodipin and triplatin did not increase blood loss, which was estimated using the tail transection method.Salivary TXA2-binding proteins, dipetalodipin and triplatin, are capable to prevent platelet-mediated NETs formation in vitro. This ability may contribute to the antithrombotic effects in vivo. Notably, both molecules inhibit arterial thrombosis without promoting excessive bleeding. Our results provide new insight into the antihemostatic effects of TXA2-binding proteins and may have important significance in elucidating the mechanisms of saliva to avoid host's hemostatic responses and innate immune system.

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

    DEFF Research Database (Denmark)

    Zhang, Wei; Zhang, Yaping; Edvinsson, Lars

    2009-01-01

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

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

    DEFF Research Database (Denmark)

    Zhang, Wei; Zhang, Yaping; Edvinsson, Lars

    2008-01-01

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

  7. Calcium modulates calmodulin/α-actinin 1 interaction with and agonist-dependent internalization of the adenosine A2A receptor.

    Science.gov (United States)

    Piirainen, Henni; Taura, Jaume; Kursula, Petri; Ciruela, Francisco; Jaakola, Veli-Pekka

    2017-04-01

    Adenosine receptors are G protein-coupled receptors that sense extracellular adenosine to transmit intracellular signals. One of the four adenosine receptor subtypes, the adenosine A 2A receptor (A 2A R), has an exceptionally long intracellular C terminus (A 2A R-ct) that mediates interactions with a large array of proteins, including calmodulin and α-actinin. Here, we aimed to ascertain the α-actinin 1/calmodulin interplay whilst binding to A 2A R and the role of Ca 2+ in this process. First, we studied the A 2A R-α-actinin 1 interaction by means of native polyacrylamide gel electrophoresis, isothermal titration calorimetry, and surface plasmon resonance, using purified recombinant proteins. α-Actinin 1 binds the A 2A R-ct through its distal calmodulin-like domain in a Ca 2+ -independent manner with a dissociation constant of 5-12μM, thus showing an ~100 times lower affinity compared to the A 2A R-calmodulin/Ca 2+ complex. Importantly, calmodulin displaced α-actinin 1 from the A 2A R-ct in a Ca 2+ -dependent fashion, disrupting the A 2A R-α-actinin 1 complex. Finally, we assessed the impact of Ca 2+ on A 2A R internalization in living cells, a function operated by the A 2A R-α-actinin 1 complex. Interestingly, while Ca 2+ influx did not affect constitutive A 2A R endocytosis, it abolished agonist-dependent internalization. In addition, we demonstrated that the A 2A R/α-actinin interaction plays a pivotal role in receptor internalization and function. Overall, our results suggest that the interplay of A 2A R with calmodulin and α-actinin 1 is fine-tuned by Ca 2+ , a fact that might power agonist-mediated receptor internalization and function. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Alternagin-C, a disintegrin-like protein from the venom of Bothrops alternatus, modulates a2ß1 integrin-mediated cell adhesion, migration and proliferation

    Directory of Open Access Journals (Sweden)

    Selistre-de-Araujo H.S.

    2005-01-01

    Full Text Available The alpha2ß1 integrin is a major collagen receptor that plays an essential role in the adhesion of normal and tumor cells to the extracellular matrix. Alternagin-C (ALT-C, a disintegrin-like protein purified from the venom of the Brazilian snake Bothrops alternatus, competitively interacts with the alpha2ß1 integrin, thereby inhibiting collagen binding. When immobilized in plate wells, ALT-C supports the adhesion of fibroblasts as well as of human vein endothelial cells (HUVEC and does not detach cells previously bound to collagen I. ALT-C is a strong inducer of HUVEC proliferation in vitro. Gene expression analysis was done using an Affimetrix HU-95A probe array with probe sets of ~10,000 human genes. In human fibroblasts growing on collagen-coated plates, ALT-C up-regulates the expression of several growth factors including vascular endothelial growth factor, as well as some cell cycle control genes. Up-regulation of the vascular endothelial growth factor gene and other growth factors could explain the positive effect on HUVEC proliferation. ALT-C also strongly activates protein kinase B phosphorylation, a signaling event involved in endothelial cell survival and angiogenesis. In human neutrophils, ALT-C has a potent chemotactic effect modulated by the intracellular signaling cascade characteristic of integrin-activated pathways. Thus, ALT-C acts as a survival factor, promoting adhesion, migration and endothelial cell proliferation after binding to alpha2ß1 integrin on the cell surface. The biological activities of ALT-C may be helpful as a therapeutic strategy in tissue regeneration as well as in the design of new therapeutic agents targeting alpha2ß1 integrin.

  9. The A2B Adenosine Receptor Modulates the Epithelial– Mesenchymal Transition through the Balance of cAMP/PKA and MAPK/ERK Pathway Activation in Human Epithelial Lung Cells

    Science.gov (United States)

    Giacomelli, Chiara; Daniele, Simona; Romei, Chiara; Tavanti, Laura; Neri, Tommaso; Piano, Ilaria; Celi, Alessandro; Martini, Claudia; Trincavelli, Maria L.

    2018-01-01

    The epithelial-mesenchymal transition (EMT) is a complex process in which cell phenotype switches from the epithelial to mesenchymal one. The deregulations of this process have been related with the occurrence of different diseases such as lung cancer and fibrosis. In the last decade, several efforts have been devoted in understanding the mechanisms that trigger and sustain this transition process. Adenosine is a purinergic signaling molecule that has been involved in the onset and progression of chronic lung diseases and cancer through the A2B adenosine receptor subtype activation, too. However, the relationship between A2BAR and EMT has not been investigated, yet. Herein, the A2BAR characterization was carried out in human epithelial lung cells. Moreover, the effects of receptor activation on EMT were investigated in the absence and presence of transforming growth factor-beta (TGF-β1), which has been known to promote the transition. The A2BAR activation alone decreased and increased the expression of epithelial markers (E-cadherin) and the mesenchymal one (Vimentin, N-cadherin), respectively, nevertheless a complete EMT was not observed. Surprisingly, the receptor activation counteracted the EMT induced by TGF-β1. Several intracellular pathways regulate the EMT: high levels of cAMP and ERK1/2 phosphorylation has been demonstrated to counteract and promote the transition, respectively. The A2BAR stimulation was able to modulated these two pathways, cAMP/PKA and MAPK/ERK, shifting the fine balance toward activation or inhibition of EMT. In fact, using a selective PKA inhibitor, which blocks the cAMP pathway, the A2BAR-mediated EMT promotion were exacerbated, and conversely the selective inhibition of MAPK/ERK counteracted the receptor-induced transition. These results highlighted the A2BAR as one of the receptors involved in the modulation of EMT process. Nevertheless, its activation is not enough to trigger a complete transition, its ability to affect different

  10. The A2B Adenosine Receptor Modulates the Epithelial– Mesenchymal Transition through the Balance of cAMP/PKA and MAPK/ERK Pathway Activation in Human Epithelial Lung Cells

    Directory of Open Access Journals (Sweden)

    Chiara Giacomelli

    2018-01-01

    Full Text Available The epithelial-mesenchymal transition (EMT is a complex process in which cell phenotype switches from the epithelial to mesenchymal one. The deregulations of this process have been related with the occurrence of different diseases such as lung cancer and fibrosis. In the last decade, several efforts have been devoted in understanding the mechanisms that trigger and sustain this transition process. Adenosine is a purinergic signaling molecule that has been involved in the onset and progression of chronic lung diseases and cancer through the A2B adenosine receptor subtype activation, too. However, the relationship between A2BAR and EMT has not been investigated, yet. Herein, the A2BAR characterization was carried out in human epithelial lung cells. Moreover, the effects of receptor activation on EMT were investigated in the absence and presence of transforming growth factor-beta (TGF-β1, which has been known to promote the transition. The A2BAR activation alone decreased and increased the expression of epithelial markers (E-cadherin and the mesenchymal one (Vimentin, N-cadherin, respectively, nevertheless a complete EMT was not observed. Surprisingly, the receptor activation counteracted the EMT induced by TGF-β1. Several intracellular pathways regulate the EMT: high levels of cAMP and ERK1/2 phosphorylation has been demonstrated to counteract and promote the transition, respectively. The A2BAR stimulation was able to modulated these two pathways, cAMP/PKA and MAPK/ERK, shifting the fine balance toward activation or inhibition of EMT. In fact, using a selective PKA inhibitor, which blocks the cAMP pathway, the A2BAR-mediated EMT promotion were exacerbated, and conversely the selective inhibition of MAPK/ERK counteracted the receptor-induced transition. These results highlighted the A2BAR as one of the receptors involved in the modulation of EMT process. Nevertheless, its activation is not enough to trigger a complete transition, its ability to

  11. Modulation of in vivo distribution through chelator: Synthesis and evaluation of a 2-nitroimidazole-dipicolylamine-(99m)Tc(CO)3 complex for detecting tumor hypoxia.

    Science.gov (United States)

    Mallia, Madhava B; Mittal, Sweety; Sarma, Haladhar D; Banerjee, Sharmila

    2016-01-01

    Previous studies have clearly demonstrated strong correlation between in vivo distribution and blood clearance of radiopharmaceuticals for the detection of hypoxia. Present study describes an attempt to improve the in vivo distribution of a previously reported 2-nitroimidazole-(99m)Tc(CO)3 complex by tuning its blood clearance pattern through structural modification of the ligand. Herein, a 2-nitroimidazole-dipicolylamine ligand (2-nitroimidazole-DPA) was synthesized in a two-step procedure and radiolabeled with (99m)Tc(CO)3 core. Subsequently, the complex was evaluated in Swiss mice bearing fibrosarcoma tumor. As intended by its design, 2-nitroimidazole-DPA-(99m)Tc(CO)3 complex was more lipophilic than previously reported 2-nitroimidazole-DETA-(99m)Tc(CO)3 complex (DETA-diethylenetriamine) and showed slower blood clearance. Consequently it showed higher tumor uptake than 2-nitroimidazole-DETA-(99m)Tc(CO)3 complex. Significantly, despite structural modifications, other parameters such as the tumor to blood ratio and tumor to muscle ratio of the 2-nitroimidazole-DPA-(99m)Tc(CO)3 complex remained comparable to that of 2-nitroimidazole-DETA-(99m)Tc(CO)3 complex. Present study demonstrates the feasibility of structural modifications for improving in vivo tumor uptake of hypoxia detecting radiopharmaceuticals. This might encourage researchers to improve suboptimal properties of a potential radiopharmaceuticals rather than ignoring it altogether. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Modulation of IgE-dependent COX-2 gene expression by reactive oxygen species in human neutrophils.

    Science.gov (United States)

    Vega, Antonio; Chacón, Pedro; Alba, Gonzalo; El Bekay, Rajaa; Martín-Nieto, José; Sobrino, Francisco

    2006-07-01

    Cyclooxygenase (COX) is a key enzyme in prostaglandin (PG) synthesis. Up-regulation of its COX-2 isoform is responsible for the increased PG release, taking place under inflammatory conditions, and also, is thought to be involved in allergic and inflammatory diseases. In the present work, we demonstrate that COX-2 expression becomes highly induced by anti-immunoglobulin E (IgE) antibodies and by antigens in human neutrophils from allergic patients. This induction was detected at mRNA and protein levels and was accompanied by a concomitant PGE(2) and thromboxane A(2) release. We also show evidence that inhibitors of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, such as 4-(2-aminoethyl)benzenesulphonyl fluoride and 4-hydroxy-3-methoxyaceto-phenone, completely cancelled anti-IgE-induced COX-2 protein up-regulation, suggesting that this process is mediated by reactive oxygen species (ROS) derived from NADPH oxidase activity. Moreover, the mitogen-activated protein kinases (MAPKs), p38 and extracellular signal-regulated kinase, and also, the transcription factor, nuclear factor (NF)-kappaB, are involved in the up-regulation of COX-2 expression, as specific chemical inhibitors of these two kinases, such as SB203580 and PD098059, and of the NF-kappaB pathway, such as N(alpha)-benzyloxycarbonyl-l-leucyl-l-leucyl-l-leucinal, abolished IgE-dependent COX-2 induction. Evidence is also presented, using Fe(2)(+)/Cu(2)(+) ions, that hydroxyl radicals generated from hydrogen peroxide through Fenton reactions could constitute candidate modulators able to directly trigger anti-IgE-elicited COX-2 expression through MAPK and NF-kappaB pathways. Present results underscore a new role for ROS as second messengers in the modulation of COX-2 expression by human neutrophils in allergic conditions.

  13. Apolipoprotein A2 -265 T>C polymorphism interacts with dietary fatty acids intake to modulate inflammation in type 2 diabetes mellitus patients.

    Science.gov (United States)

    Keramat, Laleh; Sadrzadeh-Yeganeh, Haleh; Sotoudeh, Gity; Zamani, Elham; Eshraghian, Mohammadreza; Mansoori, Anahita; Koohdani, Fariba

    2017-05-01

    Several investigations have been conducted regarding the interaction between Apolipoprotein A2 (APOA2) -265 T>C polymorphism and dietary intake of saturated fatty acids (SFAs) on obesity in healthy individuals or type 2 diabetes mellitus (T2 DM) patients. The aim of the present study is to examine the effect of this interaction on inflammatory markers in T2 DM patients. This is a comparative cross-sectional study on 180 T2 DM patients with known APOA2 genotype. Dietary intake was assessed by food-frequency questionnaire and serum levels of inflammatory markers (interleukin [IL]-18, pentraxin 3, and high-sensitivity C-reactive protein [hs-CRP]) were measured. The subjects were dichotomized into "high" and "low" categories, based on the median dietary intake of polyunsaturated fatty acids (PUFAs), monounsaturated fatty acids (MUFAs), and SFAs. The data were analyzed by analysis of covariance multivariate interaction model. In CC genotype, higher median intake of ω-3 PUFAs and MUFAs was associated with decreased serum levels of IL-18 and hs-CRP (P = 0.014 and 0.008, respectively). In T-allele carriers, higher median intake of SFAs was associated with increased serum hs-CRP level (P fatty acids, such as ω-3 PUFAs and MUFAs, could reduce the inflammatory effects associated with the CC genotype. In addition, proinflammatory fatty acids, such as SFAs, could overcome the antiinflammatory effect of the T-allele. Further studies are needed to confirm these findings. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. The dynamics of platelet α-granule membrane protein and serum thromboxane B2 in patients with acute myocardial infarction and unstable angina

    International Nuclear Information System (INIS)

    Pan Yizhi; Wu Baiming; Hong Xiaosu; Wu Guoxin; Guo Hengshan

    1997-01-01

    To evaluate the dynamics of platelet activation in patients with acute myocardial infarction (AMI) and unstable angina (UA), the levels of platelet α-granule membrane protein (GMP-140)and serum thromboxane B 2 (TXB 2 ) were studied by RIA in 20 AMI and 30 UA patients and 20 controls. The results are: 1) The levels of GMP-140 and TXB 2 were significantly higher in AMI patients within 12 h after the onset than those in controls (P 0.05). TXB 2 still remained at higher level in AMI patients on the 7th day after onset (P 2 were markedly higher in UA patients when angina episode than those in controls (P 0.05), but the peak level of GMP-140 and TXB 2 and its persistent duration of elevation in UA were much lower than those in AMI. The platelet is highly activated in the patients with AMI and UA. In AMI there are more thrombplastic factors in coronary artery than in UA

  15. Study on the correlative analysis between the changes of immunofunction status of peripheral blood red blood cells and plasma thromboxane B2 (TXB2) level in patients with pregnancy induced hypertension (PIH)

    International Nuclear Information System (INIS)

    Liu Ailing; Zhou Dongxia; Wang Yuanyuan

    2011-01-01

    Objective: To explore the relationship between changes of immunofuction status of peripheral blood red blood cells and plasma thromboxane B 2 (TXB 2 ) level in patients with PIH. Methods: RBC immunofunction status was studied with immunologic methods and plasma TXB 2 Level was measured with RIA in 33 patients with PIH and 35 normal controls.Results Level of RBC-C3bRR was significantly lower and level of plasma TXB 2 was markedly higher in the patients than those in controls (P 2 (r=0.4084, P 2 levels in patients with PIH. (authors)

  16. Model-based analysis of thromboxane B{sub 2} and prostaglandin E{sub 2} as biomarkers in the safety evaluation of naproxen

    Energy Technology Data Exchange (ETDEWEB)

    Sahota, Tarjinder; Sanderson, Ian; Danhof, Meindert [Division of Pharmacology, Leiden Academic Centre for Drug Research, Leiden (Netherlands); Della Pasqua, Oscar [Division of Pharmacology, Leiden Academic Centre for Drug Research, Leiden (Netherlands); Clinical Pharmacology Modelling and Simulation, GlaxoSmithKline, Uxbridge (United Kingdom)

    2014-08-01

    The assessment of safety in traditional toxicology protocols relies on evidence arising from observed adverse events (AEs) in animals and on establishing their correlation with different measures of drug exposure (e.g., C{sub max} and AUC). Such correlations, however, ignore the role of biomarkers, which can provide further insight into the underlying pharmacological mechanisms. Here we use naproxen as a paradigm drug to explore the feasibility of a biomarker-guided approach for the prediction of AEs in humans. A standard toxicology protocol was set up for the evaluation of effects of naproxen in rat, in which four doses were tested (7.5, 15, 40 and 80 mg/kg). In addition to sparse blood sampling for the assessment of exposure, thromboxane B{sub 2} and prostaglandin E{sub 2} were also collected in satellite groups. Nonlinear mixed effects modelling was used to evaluate the predictive performance of the approach. A one-compartmental model with first order absorption was found to best describe the pharmacokinetics of naproxen. A nonlinear relationship between dose and bioavailability was observed which leads to a less than proportional increase in naproxen concentrations with increasing doses. The pharmacodynamics of TXB{sub 2} and PGE{sub 2} was described by direct inhibition models with maximum pharmacological effects achieved at doses > 7.5 mg/kg. The predicted PKPD relationship in humans was within 10-fold of the values previously published. Moreover, our results indicate that biomarkers can be used to assess interspecies differences in PKPD and extrapolated data from animals to humans. Biomarker sampling should be used systematically in general toxicity studies. - Highlights: • Prediction of a drug's safety profile from preclinical protocols remains challenging. • Pharmacokinetic measures of safe exposure (e.g., AUC) ignore the role of biomarkers. • PKPD relationships enable the evaluation of adverse events in a mechanistic manner. • Major

  17. Presynaptic muscarinic acetylcholine autoreceptors (M1, M2 and M4 subtypes), adenosine receptors (A1 and A2A) and tropomyosin-related kinase B receptor (TrkB) modulate the developmental synapse elimination process at the neuromuscular junction.

    Science.gov (United States)

    Nadal, Laura; Garcia, Neus; Hurtado, Erica; Simó, Anna; Tomàs, Marta; Lanuza, Maria A; Santafé, Manel; Tomàs, Josep

    2016-06-23

    The development of the nervous system involves an initially exuberant production of neurons that make an excessive number of synaptic contacts. The initial overproduction of synapses promotes connectivity. Hebbian competition between axons with different activities (the least active are punished) leads to the loss of roughly half of the overproduced elements and this refines connectivity and increases specificity. The neuromuscular junction is innervated by a single axon at the end of the synapse elimination process and, because of its relative simplicity, has long been used as a model for studying the general principles of synapse development. The involvement of the presynaptic muscarinic ACh autoreceptors may allow for the direct competitive interaction between nerve endings through differential activity-dependent acetylcholine release in the synaptic cleft. Then, the most active ending may directly punish the less active ones. Our previous results indicate the existence in the weakest axons on the polyinnervated neonatal NMJ of an ACh release inhibition mechanism based on mAChR coupled to protein kinase C and voltage-dependent calcium channels. We suggest that this mechanism plays a role in the elimination of redundant neonatal synapses. Here we used confocal microscopy and quantitative morphological analysis to count the number of brightly fluorescent axons per endplate in P7, P9 and P15 transgenic B6.Cg-Tg (Thy1-YFP)16 Jrs/J mice. We investigate the involvement of individual mAChR M1-, M2- and M4-subtypes in the control of axonal elimination after the Levator auris longus muscle had been exposed to agonist and antagonist in vivo. We also analysed the role of adenosine receptor subtypes (A1 and A2A) and the tropomyosin-related kinase B receptor. The data show that postnatal axonal elimination is a regulated multireceptor mechanism that guaranteed the monoinnervation of the neuromuscular synapses. The three receptor sets considered (mAChR, AR and TrkB receptors

  18. Mercury modulates the cytochrome P450 1a1, 1a2 and 1b1 in C57BL/6J mice: in vivo and in vitro studies

    International Nuclear Information System (INIS)

    Amara, Issa E.A.; Anwar-Mohamed, Anwar; Abdelhamid, Ghada; El-Kadi, Ayman O.S.

    2013-01-01

    In the current study C57BL/6J mice were injected intraperitoneally with Hg 2+ in the absence and presence of TCDD. After 6 and 24 h the liver was harvested and the expression of Cyps was determined. In vitro, isolated hepatocytes were incubated with TCDD in the presence and absence of Hg 2+ . At the in vivo level, Hg 2+ significantly decreased the TCDD-mediated induction of Cyps at 6 h while potentiating their levels at 24 h. In vitro, Hg 2+ significantly inhibited the TCDD-mediated induction of Cyp1a1 in a concentration- and time-dependent manner. Interestingly, Hg 2+ increased the serum hemoglobin (Hb) levels in mice treated for 24 h. Upon treatment of isolated hepatocytes with Hb alone, there was an increase in the AhR-dependent luciferase activity with a subsequent increase in Cyp1a1 protein and catalytic activity levels. Importantly, when hepatocytes were treated for 2 h with Hg 2+ in the presence of TCDD, then the medium was replaced with new medium containing Hb, there was potentiation of the TCDD-mediated effect. In addition, Hg 2+ increased heme oxygenase-1 (HO-1) mRNA, which coincided with a decrease in the Cyp1a1 activity level. When the competitive HO-1 inhibitor, tin mesoporphyrin was applied to the hepatocytes there was a partial restoration of Hg 2+ -mediated inhibition of Cyp1a1 activity. In conclusion, we demonstrate for the first time that there is a differential modulation of the TCDD-mediated induction of Cyp1a1 by Hg 2+ in C57BL/6J mice livers and isolated hepatocytes. Moreover, this study implicates Hb as an in vivo specific modulator of Cyp1 family. -- Highlights: ► In vivo, Hg 2+ decreased the Cyps at 6 h while potentiating their levels at 24 h. ► In vitro, Hg 2+ significantly inhibited the TCDD-mediated induction of Cyps. ► Hg 2+ increased the serum Hb levels in animals treated for 24 h. ► Hb potentiated the TCDD-mediated effect on Cyps. ► Tin mesoporphyrin partially restored Hg 2+ -mediated inhibition of Cyp1a1.

  19. Neutrophil-induced human bronchial hyperresponsiveness in vitro--pharmacological modulation.

    Science.gov (United States)

    Hughes, J M; McKay, K O; Johnson, P R; Tragoulias, S; Black, J L; Armour, C L

    1993-04-01

    Although it has been postulated that inflammatory cells cause the bronchial hyperresponsiveness which is diagnostic of asthma, until recently there has been little direct evidence of such a link. We have recently shown that calcium ionophore-activated human neutrophils and eosinophils can induce a state of human airway hyperresponsiveness in vitro. In this study we have shown that the anti-inflammatory agent nedocromil sodium, 10(-7) M, inhibited the hyperresponsiveness induced by products released from ionophore activated neutrophils but did not inhibit the release of leukotriene B4 from the same cells. Neutrophil-induced bronchial hyperresponsiveness was also inhibited by pre-treatment of the bronchial tissues with a thromboxane A2 and prostaglandin receptor antagonist, GR32191, 10(-7) M. These findings indicate that cyclooxygenase products are involved in bronchial hyperresponsiveness induced by inflammatory cell products in vitro and that their release can be inhibited by nedocromil sodium.

  20. Irreducible Specht modules are signed Young modules

    OpenAIRE

    Hemmer, David J.

    2005-01-01

    Recently Donkin defined signed Young modules as a simultaneous generalization of Young and twisted Young modules for the symmetric group. We show that in odd characteristic, if a Specht module $S^\\lambda$ is irreducible, then $S^\\lambda$ is a signed Young module. Thus the set of irreducible Specht modules coincides with the set of irreducible signed Young modules. This provides evidence for our conjecture that the signed Young modules are precisely the class of indecomposable self-dual module...

  1. Signed Young Modules and Simple Specht Modules

    OpenAIRE

    Danz, Susanne; Lim, Kay Jin

    2015-01-01

    By a result of Hemmer, every simple Specht module of a finite symmetric group over a field of odd characteristic is a signed Young module. While Specht modules are parametrized by partitions, indecomposable signed Young modules are parametrized by certain pairs of partitions. The main result of this article establishes the signed Young module labels of simple Specht modules. Along the way we prove a number of results concerning indecomposable signed Young modules that are of independent inter...

  2. Memory Modulation

    NARCIS (Netherlands)

    Roozendaal, Benno; McGaugh, James L.

    2011-01-01

    Our memories are not all created equally strong: Some experiences are well remembered while others are remembered poorly, if at all. Research on memory modulation investigates the neurobiological processes and systems that contribute to such differences in the strength of our memories. Extensive

  3. Module descriptor

    DEFF Research Database (Denmark)

    Vincenti, Gordon; Klausen, Bodil; Kjær Jensen, Jesper

    2016-01-01

    The Module Descriptor including a Teacher’s Guide explains and describes how to work innovatively and co-creatively with wicked problems and young people. The descriptor shows how interested educators and lecturers in Europe can copy the lessons of the Erasmus+ project HIP when teaching their own...

  4. Effect of racemic ibuprofen dose on the magnitude and duration of platelet cyclo-oxygenase inhibition: relationship between inhibition of thromboxane production and the plasma unbound concentration of S(+)-ibuprofen.

    Science.gov (United States)

    Evans, A M; Nation, R L; Sansom, L N; Bochner, F; Somogyi, A A

    1991-02-01

    1. Four healthy male subjects received racemic ibuprofen (200, 400, 800 and 1200 mg), orally, on four occasions, 2 weeks apart, according to a four-way Latin-square design, in order to investigate the influence of increasing dose of ibuprofen on the magnitude and duration of its antiplatelet effect as well as on the relationship between such effect and drug concentration. 2. The antiplatelet effect of ibuprofen was assessed by measuring the inhibition of platelet thromboxane B2 (TXB2) generation during the controlled clotting of whole blood. The plasma unbound concentration of S(+)-ibuprofen, the enantiomer shown in an in vitro study to be responsible for the inhibitory effect of platelet TXB2 generation, was measured using an enantioselective method. 3. The maximum percentage inhibition of TXB2 generation increased significantly with dose from a mean +/- s.d. of 93.4 +/- 1.2% after the 200 mg dose to 98.8 +/- 0.3% after the 1200 mg dose, and there was an increase with dose in the duration of inhibition of TXB2 generation. The effect of ibuprofen on platelet TXB2 generation was transient and mirrored the time-course of unbound S(+)-ibuprofen in plasma; on all but one of the 16 occasions, serum TXB2 concentrations returned to at least within 10% of the pretreatment concentrations within 24 h of ibuprofen administration. 4. For each subject, the relationship between the percentage inhibition of TXB2 generation and the unbound concentration of S(+)-ibuprofen in plasma was modelled according to a sigmoidal Emax equation. The mean plasma unbound concentration of S(+)-ibuprofen required to inhibit platelet TXB2 generation by 50% (EC50) was 9.8 +/- 1.0 micrograms l-1.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Finite Element calculations of heat transfer for Forward SCT ModulesPart I - the Outer Module

    CERN Document Server

    Blocki, J; Perrin, E

    2000-01-01

    A status report on the thermal performance of the baseline SCT forward modules is presented. Possible design changes of the outer module which lead to significant improvements of the thermal characteristics of the module are indicated, in the context of a 2-point cooling scheme.

  6. Modulation of Phospholipase A2 Activity by Actin and Myosin.

    Science.gov (United States)

    1987-04-15

    cord vein. Thromb. Res. 18:787-795. 11. Knull. H.R.. W.F. Taylor. and W.W. Wells. 1974. Insulin effects on brain energy metabolism and the related...cells. Nature 271:549-551. I 14. Martin. T.W.. R.B. Wysolmerski. and D. Lagunoff. 1987. Phosphatidylcholine metabolism in endothelial cells: evidence for

  7. Quercetin modulates activities of Taiwan cobra phospholipase A2 ...

    Indian Academy of Sciences (India)

    2012-04-25

    Apr 25, 2012 ... Quercetin incorporation led to a reduction in PLA2 enzymatic activity and membrane-damaging activity ... membrane physical properties such as membrane fluidity or ..... eral blood mononuclear cells from diabetes patients.

  8. A 2 MHz 3-port analog isolation and fanout module

    International Nuclear Information System (INIS)

    Beadle, E.R.

    1995-01-01

    In many accelerator based data acquisition systems, signal isolation is a necessary feature so ground loops are avoided. Here, a 3-port isolated circuit providing 1:3 fanout, buffering and amplification over a multi-megahertz bandwidth is presented. The circuit accepts a single input and drives 3 independently isolated output channels, up to ± 10 V into 50 ohms. The input and output isolation is supplied via a dual optocoupler, and the power isolation is achieved with DC/DC converters. In each channel, a voltage feedback amplifier is used in combination with the optocoupler to form a transimpedance configuration with the gain-bandwidth product (GBP) set by a pair of resistors. The feedback amplifier linearizes the optocoupler transfer characteristics using a servo technique and also controls the circuit drift, nonlinearity, and bandwidth. The circuit has demonstrated long-term drift of 4 MHz, and a SNR of >55 db in a 1 MHz bandwidth with < 1% THD for a 10 V amplitude sinusoidal input. With few modifications, this design is capable of providing input/output gain and bandwidth in the range of 10--50 MHz

  9. MEMORY MODULATION

    Science.gov (United States)

    Roozendaal, Benno; McGaugh, James L.

    2011-01-01

    Our memories are not all created equally strong: Some experiences are well remembered while others are remembered poorly, if at all. Research on memory modulation investigates the neurobiological processes and systems that contribute to such differences in the strength of our memories. Extensive evidence from both animal and human research indicates that emotionally significant experiences activate hormonal and brain systems that regulate the consolidation of newly acquired memories. These effects are integrated through noradrenergic activation of the basolateral amygdala which regulates memory consolidation via interactions with many other brain regions involved in consolidating memories of recent experiences. Modulatory systems not only influence neurobiological processes underlying the consolidation of new information, but also affect other mnemonic processes, including memory extinction, memory recall and working memory. In contrast to their enhancing effects on consolidation, adrenal stress hormones impair memory retrieval and working memory. Such effects, as with memory consolidation, require noradrenergic activation of the basolateral amygdala and interactions with other brain regions. PMID:22122145

  10. Fast Convolution Module (Fast Convolution Module)

    National Research Council Canada - National Science Library

    Bierens, L

    1997-01-01

    This report describes the design and realisation of a real-time range azimuth compression module, the so-called 'Fast Convolution Module', based on the fast convolution algorithm developed at TNO-FEL...

  11. Module theory, extending modules and generalizations

    CERN Document Server

    Tercan, Adnan

    2016-01-01

    The main focus of this monograph is to offer a comprehensive presentation of known and new results on various generalizations of CS-modules and CS-rings. Extending (or CS) modules are generalizations of injective (and also semisimple or uniform) modules. While the theory of CS-modules is well documented in monographs and textbooks, results on generalized forms of the CS property as well as dual notions are far less present in the literature. With their work the authors provide a solid background to module theory, accessible to anyone familiar with basic abstract algebra. The focus of the book is on direct sums of CS-modules and classes of modules related to CS-modules, such as relative (injective) ejective modules, (quasi) continuous modules, and lifting modules. In particular, matrix CS-rings are studied and clear proofs of fundamental decomposition results on CS-modules over commutative domains are given, thus complementing existing monographs in this area. Open problems round out the work and establish the...

  12. Influence of Garlic Oil and/or Taurine Intake on Modulating the Quantity and Quality of Murine Platelets

    International Nuclear Information System (INIS)

    Amer, M.M.

    2010-01-01

    Several studies have demonstrated that enhanced platelets reactivity associated with hyperlipidaemia plays a role in the formation of atherosclerosis. Thus, platelet count, platelet aggregation in response to the agonists ADP, collagen and thromboxan B2 (TxB 2 ) were investigated in the normal and hyperlipidaemic rats to elucidate the role of some antioxidants, as modulating factors in the development of atherosclerosis. Serum concentrations of the major lipid classes, thyroid hormones, serum glutathione as well as platelet count and aggregation were determined in normal lipidemic rats (control) and compared with their corresponding levels in hyperlipidaemic ones. Hyperlipidaemia was induced by feeding rats with diet enriched with 20 g cow milk butter/100 g diet for 8 weeks. Garlic oil (200 mg/kg b.w.) and/or taurine (500 ml/kg b.w.) were peritoneal injected from the beginning of the 9th week for 15 consecutive days. Incorporation of extra fat in diet of rats for long term led to a significant (p 2 levels. On the other hand, HDL-cholesterol, serum glutathione (GSH), and T 3 and T 4 hormones level were significantly (p 2 level also showed a significant decrease. Conversely, serum HDL, T 3 , T 4 and GSH levels were significantly increased. These results denote that garlic oil and/or taurine may decrease the risk of atherosclerosis and thrombus formation associated with hyperlipidaemia through modulating the quantity and quality of platelets in male rats

  13. Human lung mast cells modulate the functions of airway smooth muscle cells in asthma.

    Science.gov (United States)

    Alkhouri, H; Hollins, F; Moir, L M; Brightling, C E; Armour, C L; Hughes, J M

    2011-09-01

    Activated mast cell densities are increased on the airway smooth muscle in asthma where they may modulate muscle functions and thus contribute to airway inflammation, remodelling and airflow obstruction. To determine the effects of human lung mast cells on the secretory and proliferative functions of airway smooth muscle cells from donors with and without asthma. Freshly isolated human lung mast cells were stimulated with IgE/anti-IgE. Culture supernatants were collected after 2 and 24 h and the mast cells lysed. The supernatants/lysates were added to serum-deprived, subconfluent airway smooth muscle cells for up to 48 h. Released chemokines and extracellular matrix were measured by ELISA, proliferation was quantified by [(3) H]-thymidine incorporation and cell counting, and intracellular signalling by phospho-arrays. Mast cell 2-h supernatants reduced CCL11 and increased CXCL8 and fibronectin production from both asthmatic and nonasthmatic muscle cells. Leupeptin reversed these effects. Mast cell 24-h supernatants and lysates reduced CCL11 release from both muscle cell types but increased CXCL8 release by nonasthmatic cells. The 24-h supernatants also reduced asthmatic, but not nonasthmatic, muscle cell DNA synthesis and asthmatic cell numbers over 5 days through inhibiting extracellular signal-regulated kinase (ERK) and phosphatidylinositol (PI3)-kinase pathways. However, prostaglandins, thromboxanes, IL-4 and IL-13 were not involved in reducing the proliferation. Mast cell proteases and newly synthesized products differentially modulated the secretory and proliferative functions of airway smooth muscle cells from donors with and without asthma. Thus, mast cells may modulate their own recruitment and airway smooth muscle functions locally in asthma. © 2011 John Wiley & Sons A/S.

  14. Reduced multiplication modules

    Indian Academy of Sciences (India)

    if M is a von Neumann regular module (VNM); i.e., every principal submodule of M is a summand submodule. Also if M is an injective R-module, then M is a VNM. Keywords. Multiplication module; reduced module; minimal prime submodule;. Zariski topology; extremally disconnected. 1. Introduction. In this paper all rings are ...

  15. Modulational effects in accelerators

    International Nuclear Information System (INIS)

    Satogata, T.

    1997-01-01

    We discuss effects of field modulations in accelerators, specifically those that can be used for operational beam diagnostics and beam halo control. In transverse beam dynamics, combined effects of nonlinear resonances and tune modulations influence diffusion rates with applied tune modulation has been demonstrated. In the longitudinal domain, applied RF phase and voltage modulations provide mechanisms for parasitic halo transport, useful in slow crystal extraction. Experimental experiences with transverse tune and RF modulations are also discussed

  16. 2D Finite Element Model of a CIGS Module

    Energy Technology Data Exchange (ETDEWEB)

    Janssen, G.J.M.; Slooff, L.H.; Bende, E.E. [ECN Solar Energy, P.O.Box 1, NL-1755 ZG Petten (Netherlands)

    2012-06-15

    The performance of thin-film CIGS (Copper indium gallium selenide) modules is often limited due to inhomogeneities in CIGS layers. A 2-dimensional Finite Element Model for CIGS modules is presented that predicts the impact of such inhomogeneities on the module performance. Results are presented of a module with a region of poor diode characteristics. It is concluded that according to this model the effects of poor diodes depend strongly on their location in the module and on their dispersion over the module surface. Due to its generic character the model can also be applied to other series connections of photovoltaic cells.

  17. 2D - Finite element model of a CIGS module

    Energy Technology Data Exchange (ETDEWEB)

    Janssen, G.J.M.; Slooff, L.H.; Bende, E.E. [ECN Solar Energy, Petten (Netherlands)

    2012-09-15

    The performance of thin-film CIGS modules is often limited due to inhomogeneities in CIGS layers. A 2-dimensional Finite Element Model for CIGS modules is demonstrated that predicts the impact of such inhomogeneities on the module performance. Results are presented of a module with a region of poor diode characteristics. It is concluded that according to this model the effects of poor diodes depend strongly on their location in the module and on their dispersion over the module surface. Due to its generic character the model can also be applied to other series connections of photovoltaic cells.

  18. Crossed Module Bundle Gerbes; Classification, String Group and Differential Geometry

    OpenAIRE

    Jurco, Branislav

    2005-01-01

    We discuss nonabelian bundle gerbes and their differential geometry using simplicial methods. Associated to any crossed module there is a simplicial group NC, the nerve of the 1-category defined by the crossed module and its geometric realization |NC|. Equivalence classes of principal bundles with structure group |NC| are shown to be one-to-one with stable equivalence classes of what we call crossed module gerbes bundle gerbes. We can also associate to a crossed module a 2-category C'. Then t...

  19. Partial purification and identification of the thrombozane A2/prostaglandin H2 receptor protein in human platelets

    International Nuclear Information System (INIS)

    Lim, C.T.; Kattelman, E.J.; Arora, S.K.; Venton, D.L.; Le Breton, G.C.

    1986-01-01

    The thromboxane A 2 /prostaglandin H 2 (TXA 2 /PGH 2 ) receptor antagonist [ 3 H]-13-azaprostanoic acid (13-APA) was used to identify and purify the platelet TXA 2 /PGH 2 receptor protein. Optimal solubilization of the 13-APA binding protein was achieved by extraction with 3-[(3-cholamidopropyl)dimethyl-ammonio]-1-propanesulfonate (CHAPS) detergent. Preliminary purification of the crude solubilized membrane fraction was performed by gel filtration chromatography using a Sepharose 4B column. Further purification was accomplished by high performance liquid chromatography (HPLC) using a Synchropak GPC-500 column. The HPLC protein profile revealed two protein peaks, only one of which was enriched in [ 3 H]-13-APA. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of this peak revealed two bands with molecular weights of 65,000 and 60,000 daltons. In binding studies using the 60,000 dalton-enriched subfraction, unlabelled 13-APA, the TXA 2 /PGH 2 mimetic U46619 and the TXA 2 /PGH 2 antagonist SQ 29,548 all competed for [ 3 H]-13-APA binding whereas TXB 2 did not compete for binding. Heat denaturation of this subfraction resulted in a complete loss of binding activity. These findings indicate that a protein of approximately 60,000 daltons represents the human platelet TXA 2 /PGH 2 receptor

  20. Electroabsorption optical modulator

    Energy Technology Data Exchange (ETDEWEB)

    Skogen, Erik J.

    2017-11-21

    An electroabsorption modulator incorporates waveguiding regions along the length of the modulator that include quantum wells where at least two of the regions have quantum wells with different bandgaps. In one embodiment of the invention, the regions are arranged such that the quantum wells have bandgaps with decreasing bandgap energy along the length of the modulator from the modulator's input to its output. The bandgap energy of the quantum wells may be decreased in discrete steps or continuously. Advantageously, such an arrangement better distributes the optical absorption as well as the carrier density along the length of the modulator. Further advantageously, the modulator may handle increased optical power as compared with prior art modulators of similar dimensions, which allows for improved link gain when the optical modulator is used in an analog optical communication link.

  1. CDC 7600 module slice

    CERN Multimedia

    Each module contained 8 circuit cards for a total of about 300-500 uncovered transistors packaged with face plates so the Freon plates wouldn't touch the circuits. (cooling plates that surrounded each module).

  2. Exploration Augmentation Module Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The Exploration Augmentation Module (EAM) project goal is to design and deliver a flight module that is to be deployed to Earth-Lunar Distant Retrograde Orbit (DRO)....

  3. CDC 6600 Cordwood Module

    CERN Multimedia

    1964-01-01

    The CDC 6600 cordwood module containing 64 silicon transistors. The module was mounted between two plates that were cooled conductive by a refrigeration unit via the front panel. The construction of this module uses the cord method, so called because the resistors seem to be stacked like cord between the two circuit boards in order to obtain a high density. The 6600 model contained nearly 6,000 such modules.

  4. Modulating lignin in plants

    Science.gov (United States)

    Apuya, Nestor; Bobzin, Steven Craig; Okamuro, Jack; Zhang, Ke

    2013-01-29

    Materials and methods for modulating (e.g., increasing or decreasing) lignin content in plants are disclosed. For example, nucleic acids encoding lignin-modulating polypeptides are disclosed as well as methods for using such nucleic acids to generate transgenic plants having a modulated lignin content.

  5. An investigation into modulators

    International Nuclear Information System (INIS)

    Heine, E.

    1988-01-01

    In the framework of the MEA-update it is important to establish which modulators are necessary. In this report it is lookedif the existing modulators can be maintained or new modulators have to be made. Besides technical aspects also material expenses and necessary manpower play a role. 12 figs.; 6 tabs

  6. Weakly Coretractable Modules

    Science.gov (United States)

    Hadi, Inaam M. A.; Al-aeashi, Shukur N.

    2018-05-01

    If R is a ring with identity and M is a unitary right R-module. Here we introduce the class of weakly coretractable module. Some basic properties are investigated and some relationships between these modules and other related one are introduced.

  7. Amplitude modulation detection with concurrent frequency modulation.

    Science.gov (United States)

    Nagaraj, Naveen K

    2016-09-01

    Human speech consists of concomitant temporal modulations in amplitude and frequency that are crucial for speech perception. In this study, amplitude modulation (AM) detection thresholds were measured for 550 and 5000 Hz carriers with and without concurrent frequency modulation (FM), at AM rates crucial for speech perception. Results indicate that adding 40 Hz FM interferes with AM detection, more so for 5000 Hz carrier and for frequency deviations exceeding the critical bandwidth of the carrier frequency. These findings suggest that future cochlear implant processors, encoding speech fine-structures may consider limiting the FM to narrow bandwidth and to low frequencies.

  8. Divisible ℤ-modules

    Directory of Open Access Journals (Sweden)

    Futa Yuichi

    2016-03-01

    Full Text Available In this article, we formalize the definition of divisible ℤ-module and its properties in the Mizar system [3]. We formally prove that any non-trivial divisible ℤ-modules are not finitely-generated.We introduce a divisible ℤ-module, equivalent to a vector space of a torsion-free ℤ-module with a coefficient ring ℚ. ℤ-modules are important for lattice problems, LLL (Lenstra, Lenstra and Lovász base reduction algorithm [15], cryptographic systems with lattices [16] and coding theory [8].

  9. Classes of modules

    CERN Document Server

    Dauns, John

    2006-01-01

    Because traditional ring theory places restrictive hypotheses on all submodules of a module, its results apply only to small classes of already well understood examples. Often, modules with infinite Goldie dimension have finite-type dimension, making them amenable to use with type dimension, but not Goldie dimension. By working with natural classes and type submodules (TS), Classes of Modules develops the foundations and tools for the next generation of ring and module theory. It shows how to achieve positive results by placing restrictive hypotheses on a small subset of the complement submodules, Furthermore, it explains the existence of various direct sum decompositions merely as special cases of type direct sum decompositions. Carefully developing the foundations of the subject, the authors begin by providing background on the terminology and introducing the different module classes. The modules classes consist of torsion, torsion-free, s[M], natural, and prenatural. They expand the discussion by exploring...

  10. FASTBUS Snoop Diagnostic Module

    International Nuclear Information System (INIS)

    Walz, H.V.; Downing, R.

    1980-11-01

    Development of the FASTBUS Snoop Module, undertaken as part of the prototype program for the new interlaboratory data bus standard, is described. The Snoop Module resides on a FASTBUS crate segment and provides diagnostic monitoring and testing capability. Communication with a remote host computer is handled independent of FASTBUS through a serial link. The module consists of a high-speed ECL front-end to monitor and single-step FASTBUS cycles, a master-slave interface, and a control microprocessor with serial communication ports. Design details and performance specifications of the prototype module are reported. 9 figures, 1 table

  11. Bracket for photovoltaic modules

    Science.gov (United States)

    Ciasulli, John; Jones, Jason

    2014-06-24

    Brackets for photovoltaic ("PV") modules are described. In one embodiment, a saddle bracket has a mounting surface to support one or more PV modules over a tube, a gusset coupled to the mounting surface, and a mounting feature coupled to the gusset to couple to the tube. The gusset can have a first leg and a second leg extending at an angle relative to the mounting surface. Saddle brackets can be coupled to a torque tube at predetermined locations. PV modules can be coupled to the saddle brackets. The mounting feature can be coupled to the first gusset and configured to stand the one or more PV modules off the tube.

  12. Crossed modules of racks

    OpenAIRE

    Crans, Alissa S.; Wagemann, Friedrich

    2014-01-01

    We generalize the notion of a crossed module of groups to that of a crossed module of racks. We investigate the relation to categorified racks, namely strict 2-racks, and trunk-like objects in the category of racks, generalizing the relation between crossed modules of groups and strict 2-groups. Then we explore topological applications. We show that by applying the rack-space functor, a crossed module of racks gives rise to a covering. Our main result shows how the fundamental racks associate...

  13. Model theory and modules

    CERN Document Server

    Prest, M

    1988-01-01

    In recent years the interplay between model theory and other branches of mathematics has led to many deep and intriguing results. In this, the first book on the topic, the theme is the interplay between model theory and the theory of modules. The book is intended to be a self-contained introduction to the subject and introduces the requisite model theory and module theory as it is needed. Dr Prest develops the basic ideas concerning what can be said about modules using the information which may be expressed in a first-order language. Later chapters discuss stability-theoretic aspects of module

  14. Delphi Accounts Receivable Module -

    Data.gov (United States)

    Department of Transportation — Delphi accounts receivable module contains the following data elements, but are not limited to customer information, cash receipts, line of accounting details, bill...

  15. Phenotypic approaches to gene mapping in platelet function disorders - identification of new variant of P2Y12, TxA2 and GPVI receptors.

    Science.gov (United States)

    Watson, S; Daly, M; Dawood, B; Gissen, P; Makris, M; Mundell, S; Wilde, J; Mumford, A

    2010-01-01

    Platelet number or function disorders cause a range of bleeding symptoms from mild to severe. Patients with platelet dysfunction but normal platelet number are the most prevalent and typically have mild bleeding symptoms. The study of this group of patients is particularly difficult because of the lack of a gold-standard test of platelet function and the variable penetrance of the bleeding phenotype among affected individuals. The purpose of this short review is to discuss the way in which this group of patients can be investigated through platelet phenotyping in combination with targeted gene sequencing. This approach has been used recently to identify patients with mutations in key platelet activation receptors, namely those for ADP, collagen and thromboxane A2 (TxA2). One interesting finding from this work is that for some patients, mild bleeding is associated with heterozygous mutations in platelet proteins that are co-inherited with other genetic disorders of haemostasis such as type 1 von Willebrand's disease. Thus, the phenotype of mild bleeding may be multifactorial in some patients and may be considered to be a complex trait.

  16. Inherited human group IVA cytosolic phospholipase A2 deficiency abolishes platelet, endothelial, and leucocyte eicosanoid generation

    Science.gov (United States)

    Kirkby, Nicholas S.; Reed, Daniel M.; Edin, Matthew L.; Rauzi, Francesca; Mataragka, Stefania; Vojnovic, Ivana; Bishop-Bailey, David; Milne, Ginger L.; Longhurst, Hilary; Zeldin, Darryl C.; Mitchell, Jane A.; Warner, Timothy D.

    2016-01-01

    Eicosanoids are important vascular regulators, but the phospholipase A2 (PLA2) isoforms supporting their production within the cardiovascular system are not fully understood. To address this, we have studied platelets, endothelial cells, and leukocytes from 2 siblings with a homozygous loss-of-function mutation in group IVA cytosolic phospholipase A2 (cPLA2α). Chromatography/mass spectrometry was used to determine levels of a broad range of eicosanoids produced by isolated vascular cells, and in plasma and urine. Eicosanoid release data were paired with studies of cellular function. Absence of cPLA2α almost abolished eicosanoid synthesis in platelets (e.g., thromboxane A2, control 20.5 ± 1.4 ng/ml vs. patient 0.1 ng/ml) and leukocytes [e.g., prostaglandin E2 (PGE2), control 21.9 ± 7.4 ng/ml vs. patient 1.9 ng/ml], and this was associated with impaired platelet activation and enhanced inflammatory responses. cPLA2α-deficient endothelial cells showed reduced, but not absent, formation of prostaglandin I2 (prostacyclin; control 956 ± 422 pg/ml vs. patient 196 pg/ml) and were primed for inflammation. In the urine, prostaglandin metabolites were selectively influenced by cPLA2α deficiency. For example, prostacyclin metabolites were strongly reduced (18.4% of control) in patients lacking cPLA2α, whereas PGE2 metabolites (77.8% of control) were similar to healthy volunteer levels. These studies constitute a definitive account, demonstrating the fundamental role of cPLA2α to eicosanoid formation and cellular responses within the human circulation.—Kirkby, N. S., Reed, D. M., Edin, M. L., Rauzi, F., Mataragka, S., Vojnovic, I., Bishop-Bailey, D., Milne, G. L., Longhurst, H., Zeldin, D. C., Mitchell, J. A., Warner, T. D. Inherited human group IVA cytosolic phospholipase A2 deficiency abolishes platelet, endothelial, and leucocyte eicosanoid generation. PMID:26183771

  17. Growth Modulation in Achondroplasia.

    Science.gov (United States)

    McClure, Philip K; Kilinc, Eray; Birch, John G

    2017-09-01

    Achondroplasia is the most common skeletal dysplasia with a rate of nearly 1/10,000. The development of lower extremity deformity is well documented, and various modes of correction have been reported. There are no reports on the use of growth modulation to correct angular deformity in achondroplasia. Medical Records from 1985 to 2015 were reviewed for the diagnosis of achondroplasia and growth modulation procedures. Patients who had been treated for angular deformity of the legs by growth modulation were identified. A detailed analysis of their medical record and preoperative and final lower extremity radiographs was completed. Four patients underwent growth modulation procedures, all to correct existing varus deformity of the legs. Three of the 4 patients underwent bilateral distal femoral and proximal tibial growth modulation. The remaining patient underwent tibial correction only. Two of the 4 patients had a combined proximal fibular epiphysiodesis. All limbs had some improvement of alignment; however, 1 patient went on to bilateral osteotomies. Only 1 limb corrected to a neutral axis with growth modulation alone at last follow-up, initial implantation was done before 5 years of age. Growth modulation is an effective means for deformity correction in the setting of achondroplasia. However implantation may need to be done earlier than would be typical for patients without achondroplasia. Osteotomy may still be required after growth modulation for incomplete correction.

  18. Defect detection module

    International Nuclear Information System (INIS)

    Ernwein, R.; Westermann, G.

    1986-01-01

    The ''defect detector'' module is aimed at exceptional event or state recording. Foreseen for voltage presence monitoring on high supply voltage module of drift chambers, its characteristics can also show up the vanishing of supply voltage and take in account transitory fast signals [fr

  19. The Strip Module

    DEFF Research Database (Denmark)

    Pedersen, Tommy

    1996-01-01

    When the behaviour of a ship in waves is to be predicted it is convenient to have a tool which includes different approaches to the problem.The aim of this project is to develop such a tool named the strip theory module. The strip theory module will consist of submodules dependent on the I...

  20. The FPAX fastbus module

    International Nuclear Information System (INIS)

    Barlag, S.; Bouquet, B.; Lavigne, B.; Rypko, J.

    1989-07-01

    The FPAX is a Fastbus module with 4 independent, 2 slave and 2 master, ports on two segments. It operates as a normal master on either segment or as a Block-Mover on both. The processor board is based on a 68020 microprocessor. A local/network switch allows operation as a host or as a normal module on the Fastbus network

  1. Photovoltaic module and laminate

    Science.gov (United States)

    Bunea, Gabriela E.; Kim, Sung Dug; Kavulak, David F.J.

    2018-04-10

    A photovoltaic module is disclosed. The photovoltaic module has a first side directed toward the sun during normal operation and a second, lower side. The photovoltaic module comprises a perimeter frame and a photovoltaic laminate at least partially enclosed by and supported by the perimeter frame. The photovoltaic laminate comprises a transparent cover layer positioned toward the first side of the photovoltaic module, an upper encapsulant layer beneath and adhering to the cover layer, a plurality of photovoltaic solar cells beneath the upper encapsulant layer, the photovoltaic solar cells electrically interconnected, a lower encapsulant layer beneath the plurality of photovoltaic solar cells, the upper and lower encapsulant layers enclosing the plurality of photovoltaic solar cells, and a homogenous rear environmental protection layer, the rear environmental protection layer adhering to the lower encapsulant layer, the rear environmental protection layer exposed to the ambient environment on the second side of the photovoltaic module.

  2. Solar energy modulator

    Science.gov (United States)

    Hale, R. R. (Inventor); Mcdougal, A. R.

    1984-01-01

    A module is described with a receiver having a solar energy acceptance opening and supported by a mounting ring along the optic axis of a parabolic mirror in coaxial alignment for receiving solar energy from the mirror, and a solar flux modulator plate for varying the quantity of solar energy flux received by the acceptance opening of the module. The modulator plate is characterized by an annular, plate-like body, the internal diameter of which is equal to or slightly greater than the diameter of the solar energy acceptance opening of the receiver. Slave cylinders are connected to the modulator plate for supporting the plate for axial displacement along the axis of the mirror, therby shading the opening with respect to solar energy flux reflected from the surface of the mirror to the solar energy acceptance opening.

  3. X-(2) Modulator With 40-GHz Modulation Utilizing BaTiO3 Photonic Crystal Waveguides

    DEFF Research Database (Denmark)

    Girouard, Peter David; Chen, Pice; Jeong, Young Kyu

    2017-01-01

    Future telecommunication and data center networks as well as quantum optical communication systems will require optical modulators with wide bandwidths, large extinction, low operating voltage, and small size. We report the first quantitative demonstration of slow light enhancement of the electro......-optic (EO) coefficient in a.(2) ferroelectric waveguide at microwave modulation frequencies. This is demonstrated in a compact (1 mm) photonic crystal (PC) device with a voltage-length product (V pi . L) of 0.66 V-cm at 10 GHz and measured EO modulation out to 40 GHz. A local enhancement factor of 12...

  4. Photovoltaic module and interlocked stack of photovoltaic modules

    Science.gov (United States)

    Wares, Brian S.

    2014-09-02

    One embodiment relates to an arrangement of photovoltaic modules configured for transportation. The arrangement includes a plurality of photovoltaic modules, each photovoltaic module including a frame. A plurality of individual male alignment features and a plurality of individual female alignment features are included on each frame. Adjacent photovoltaic modules are interlocked by multiple individual male alignment features on a first module of the adjacent photovoltaic modules fitting into and being surrounded by corresponding individual female alignment features on a second module of the adjacent photovoltaic modules. Other embodiments, features and aspects are also disclosed.

  5. The ANTARES optical module

    Energy Technology Data Exchange (ETDEWEB)

    Amram, P.; Anghinolfi, M.; Anvar, S.; Ardellier-Desages, F.E.; Aslanides, E.; Aubert, J.-J.; Azoulay, R.; Bailey, D.; Basa, S.; Battaglieri, M.; Bellotti, R.; Benhammou, Y.; Bernard, F.; Berthier, R.; Bertin, V.; Billault, M.; Blaes, R.; Bland, R.W.; Blondeau, F.; Botton, N. de; Boulesteix, J.; Brooks, C.B.; Brunner, J.; Cafagna, F.; Calzas, A.; Capone, A.; Caponetto, L.; Carloganu, C.; Carmona, E.; Carr, J.; Carton, P.-H.; Cartwright, S.L.; Cassol, F.; Cecchini, S.; Ciacio, F.; Circella, M.; Compere, C.; Cooper, S.; Coyle, P.; Croquette, J.; Cuneo, S.; Danilov, M.; Dantzig, R. van; De Marzo, C.; DeVita, R.; Deck, P.; Destelle, J.-J.; Dispau, G.; Drougou, J.F.; Druillole, F.; Engelen, J.; Feinstein, F.; Festy, D.; Fopma, J.; Gallone, J.-M.; Giacomelli, G.; Goret, P.; Gosset, L.; Gournay, J.-F.; Heijboer, A.; Hernandez-Rey, J.J.; Herrouin, G.; Hubbard, J.R.; Jaquet, M.; Jong, M. de; Karolak, M.; Kooijman, P.; Kouchner, A.; Kudryavtsev, V.A.; Lachartre, D.; Lafoux, H. E-mail: lafoux@cea.fr; Lamare, P.; Languillat, J.-C.; Laubier, L.; Laugier, J.-P.; Le Guen, Y.; Le Provost, H.; Le Van Suu, A.; Lemoine, L.; Lo Nigro, L.; Lo Presti, D.; Loucatos, S.; Louis, F.; Lyashuk, V.; Magnier, P.; Marcelin, M.; Margiotta, A.; Massol, A.; Masullo, R.; Mazeas, F.; Mazeau, B.; Mazure, A.; McMillan, J.E.; Michel, J.L.; Migneco, E.; Millot, C.; Mols, P.; Montanet, F.; Montaruli, T.; Morel, J.P.; Moscoso, L.; Musumeci, M.; Navas, S.; Nezri, E.; Nooren, G.J.; Oberski, J.; Olivetto, C.; Oppelt-Pohl, A.; Palanque-Delabrouille, N.; Papaleo, R.; Payre, P.; Perrin, P.; Petruccetti, M.; Petta, C.; Piattelli, P.; Poinsignon, J.; Potheau, R.; Queinec, Y.; Racca, C.; Raia, G.; Randazzo, N.; Rethore, F.; Riccobene, G.; Ricol, J.-S.; Ripani, M.; Roca-Blay, V.; Rolin, J.F.; Rostovstev, A.; Russo, G.V.; Sacquin, Y.; Salusti, E.; Schuller, J.-P.; Schuster, W.; Soirat, J.-P.; Souvorova, O.; Spooner, N.J.C.; Spurio, M.; Stolarczyk, T.; Stubert, D.; Taiuti, M.; Tao, C.; Tayalati, Y.; Thompson, L.F.

    2002-05-21

    The ANTARES collaboration is building a deep sea neutrino telescope in the Mediterranean Sea. This detector will cover a sensitive area of typically 0.1 km{sup 2} and will be equipped with about 1000 optical modules. Each of these optical modules consists of a large area photomultiplier and its associated electronics housed in a pressure resistant glass sphere. The design of the ANTARES optical module, which is a key element of the detector, has been finalized following extensive R and D studies and is reviewed here in detail.

  6. The ANTARES optical module

    International Nuclear Information System (INIS)

    Amram, P.; Anghinolfi, M.; Anvar, S.; Ardellier-Desages, F.E.; Aslanides, E.; Aubert, J.-J.; Azoulay, R.; Bailey, D.; Basa, S.; Battaglieri, M.; Bellotti, R.; Benhammou, Y.; Bernard, F.; Berthier, R.; Bertin, V.; Billault, M.; Blaes, R.; Bland, R.W.; Blondeau, F.; Botton, N. de; Boulesteix, J.; Brooks, C.B.; Brunner, J.; Cafagna, F.; Calzas, A.; Capone, A.; Caponetto, L.; Carloganu, C.; Carmona, E.; Carr, J.; Carton, P.-H.; Cartwright, S.L.; Cassol, F.; Cecchini, S.; Ciacio, F.; Circella, M.; Compere, C.; Cooper, S.; Coyle, P.; Croquette, J.; Cuneo, S.; Danilov, M.; Dantzig, R. van; De Marzo, C.; DeVita, R.; Deck, P.; Destelle, J.-J.; Dispau, G.; Drougou, J.F.; Druillole, F.; Engelen, J.; Feinstein, F.; Festy, D.; Fopma, J.; Gallone, J.-M.; Giacomelli, G.; Goret, P.; Gosset, L.; Gournay, J.-F.; Heijboer, A.; Hernandez-Rey, J.J.; Herrouin, G.; Hubbard, J.R.; Jaquet, M.; Jong, M. de; Karolak, M.; Kooijman, P.; Kouchner, A.; Kudryavtsev, V.A.; Lachartre, D.; Lafoux, H.; Lamare, P.; Languillat, J.-C.; Laubier, L.; Laugier, J.-P.; Le Guen, Y.; Le Provost, H.; Le Van Suu, A.; Lemoine, L.; Lo Nigro, L.; Lo Presti, D.; Loucatos, S.; Louis, F.; Lyashuk, V.; Magnier, P.; Marcelin, M.; Margiotta, A.; Massol, A.; Masullo, R.; Mazeas, F.; Mazeau, B.; Mazure, A.; McMillan, J.E.; Michel, J.L.; Migneco, E.; Millot, C.; Mols, P.; Montanet, F.; Montaruli, T.; Morel, J.P.; Moscoso, L.; Musumeci, M.; Navas, S.; Nezri, E.; Nooren, G.J.; Oberski, J.; Olivetto, C.; Oppelt-Pohl, A.; Palanque-Delabrouille, N.; Papaleo, R.; Payre, P.; Perrin, P.; Petruccetti, M.; Petta, C.; Piattelli, P.; Poinsignon, J.; Potheau, R.; Queinec, Y.; Racca, C.; Raia, G.; Randazzo, N.; Rethore, F.; Riccobene, G.; Ricol, J.-S.; Ripani, M.; Roca-Blay, V.; Rolin, J.F.; Rostovstev, A.; Russo, G.V.; Sacquin, Y.; Salusti, E.; Schuller, J.-P.; Schuster, W.; Soirat, J.-P.; Souvorova, O.; Spooner, N.J.C.; Spurio, M.; Stolarczyk, T.; Stubert, D.; Taiuti, M.; Tao, C.; Tayalati, Y.; Thompson, L.F.; Tilav, S.; Triay, R.; Valente, V.; Varlamov, I.; Vaudaine, G.; Vernin, P.; Witt Huberts, P. de; Wolf, E. de; Zakharov, V.; Zavatarelli, S.; D Zornoza, J. de; Zuniga, J.

    2002-01-01

    The ANTARES collaboration is building a deep sea neutrino telescope in the Mediterranean Sea. This detector will cover a sensitive area of typically 0.1 km 2 and will be equipped with about 1000 optical modules. Each of these optical modules consists of a large area photomultiplier and its associated electronics housed in a pressure resistant glass sphere. The design of the ANTARES optical module, which is a key element of the detector, has been finalized following extensive R and D studies and is reviewed here in detail

  7. The ANTARES Optical Module

    CERN Document Server

    Amram, P; Anvar, S; Ardellier-Desages, F E; Aslanides, Elie; Aubert, Jean-Jacques; Azoulay, R; Bailey, D; Basa, S; Battaglieri, M; Bellotti, R; Benhammou, Ya; Bernard, F; Berthier, R; Bertin, V; Billault, M; Blaes, R; Bland, R W; Blondeau, F; De Botton, N R; Boulesteix, J; Brooks, B; Brunner, J; Cafagna, F; Calzas, A; Capone, A; Caponetto, L; Cârloganu, C; Carmona, E; Carr, J; Carton, P H; Cartwright, S L; Cassol, F; Cecchini, S; Ciacio, F; Circella, M; Compere, C; Cooper, S; Coyle, P; Croquette, J; Cuneo, S; Danilov, M; Van Dantzig, R; De Marzo, C; De Vita, R; Deck, P; Destelle, J J; Dispau, G; Drougou, J F; Druillole, F; Engelen, J; Feinstein, F; Festy, D; Fopma, J; Gallone, J M; Giacomelli, G; Goret, P; Gosset, L G; Gournay, J F; Heijboer, A; Hernández-Rey, J J; Herrouin, G; Hubbard, John R; Jacquet, M; De Jong, M; Karolak, M; Kooijman, P M; Kouchner, A; Kudryavtsev, V A; Lachartre, D; Lafoux, H; Lamare, P; Languillat, J C; Laubier, L; Laugier, J P; Le Guen, Y; Le Provost, H; Le Van-Suu, A; Lemoine, L; Lo Nigro, L; Lo Presti, D; Loucatos, Sotirios S; Louis, F; Lyashuk, V I; Magnier, P; Marcelin, M; Margiotta, A; Massol, A; Masullo, R; Mazéas, F; Mazeau, B; Mazure, A; McMillan, J E; Michel, J L; Migneco, E; Millot, C; Mols, P; Montanet, François; Montaruli, T; Morel, J P; Moscoso, L; Navas, S; Nezri, E; Nooren, G J L; Oberski, J; Olivetto, C; Oppelt-pohl, A; Palanque-Delabrouille, Nathalie; Payre, P; Perrin, P; Petruccetti, M; Petta, P; Piattelli, P; Poinsignon, J; Popa, V; Potheau, R; Queinec, Y; Racca, C; Raia, G; Randazzo, N; Rethore, F; Riccobene, G; Ricol, J S; Ripani, M; Roca-Blay, V; Rolin, J F; Rostovtsev, A A; Russo, G V; Sacquin, Yu; Salusti, E; Schuller, J P; Schuster, W; Soirat, J P; Suvorova, O; Spooner, N J C; Spurio, M; Stolarczyk, T; Stubert, D; Taiuti, M; Tao, Charling; Tayalati, Y; Thompson, L F; Tilav, S; Triay, R; Valente, V; Varlamov, I; Vaudaine, G; Vernin, P; De Witt-Huberts, P K A; De Wolf, E; Zakharov, V; Zavatarelli, S; De Dios-Zornoza-Gomez, Juan; Zúñiga, J

    2002-01-01

    The ANTARES collaboration is building a deep sea neutrino telescope in the Mediterranean Sea. This detector will cover a sensitive area of typically 0.1 km-squared and will be equipped with about 1000 optical modules. Each of these optical modules consists of a large area photomultiplier and its associated electronics housed in a pressure resistant glass sphere. The design of the ANTARES optical module, which is a key element of the detector, has been finalized following extensive R & D studies and is reviewed here in detail.

  8. Frames in super Hilbert modules

    Directory of Open Access Journals (Sweden)

    Mehdi Rashidi-Kouchi

    2018-01-01

    Full Text Available In this paper, we define super Hilbert module and investigate frames in this space. Super Hilbert modules are  generalization of super Hilbert spaces in Hilbert C*-module setting. Also, we define frames in a super Hilbert module and characterize them by using of the concept of g-frames in a Hilbert C*-module. Finally, disjoint frames in Hilbert C*-modules are introduced and investigated.

  9. A photovoltaic module

    DEFF Research Database (Denmark)

    2013-01-01

    The present invention relates to a photovoltaic module comprising a carrier substrate, said carrier substrate carrying a purely printed structure comprising printed positive and negative module terminals, a plurality of printed photovoltaic cell units each comprising one or more printed...... photovoltaic cells, wherein the plurality of printed photovoltaic cell units are electrically connected in series between the positive and the negative module terminals such that any two neighbouring photovoltaic cell units are electrically connected by a printed interconnecting electrical conductor....... The carrier substrate comprises a foil and the total thickness of the photovoltaic module is below 500 [mu]m. Moreover, the nominal voltage level between the positive and the negative terminals is at least 5 kV DC....

  10. Strain-Modulated Epitaxy

    National Research Council Canada - National Science Library

    Brown, April

    1999-01-01

    Strain-Modulated Epitaxy (SME) is a novel approach, invented at Georgia Tech, to utilize subsurface stressors to control strain and therefore material properties and growth kinetics in the material above the stressors...

  11. Solid state detector module

    International Nuclear Information System (INIS)

    Hoffman, D. M.

    1985-01-01

    A solid state detector in which each scintillator is optimally configured and coupled with its associated sensing diode in a way which exploits light piping effects to enhance efficiency, and at the same time provide a detector which is modular in nature. To achieve light piping, the scintillator crystal is oriented such that its sides conform with the crystal cleavage plane, and the sides are highly polished. An array of tungsten collimator plates define the individual channels. Multi-channel scintillator/diode modules are mounted behind and in registry with the plurality of collimator plates. A plurality of scintillators are bonded together after coating the surfaces thereof to minimize optical crosstalk. After lapping the face of the scintillator module, it is then bonded to a diode module with individual scintillators in registration with individual diodes. The module is then positioned in the detector array with collimator plates at the junctions between the scintillators

  12. Periodically modulated dark states

    Science.gov (United States)

    Han, Yingying; Zhang, Jun; Zhang, Wenxian

    2018-04-01

    Phenomena of electromagnetically induced transparency (PEIT) may be interpreted by the Autler-Townes Splitting (ATS), where the coupled states are split by the coupling laser field, or by the quantum destructive interference (QDI), where the atomic phases caused by the coupling laser and the probe laser field cancel. We propose modulated experiments to explore the PEIT in an alternative way by periodically modulating the coupling and the probe fields in a Λ-type three-level system initially in a dark state. Our analytical and numerical results rule out the ATS interpretation and show that the QDI interpretation is more appropriate for the modulated experiments. Interestingly, dark state persists in the double-modulation situation where control and probe fields never occur simultaneously, which is significant difference from the traditional dark state condition. The proposed experiments are readily implemented in atomic gases, artificial atoms in superconducting quantum devices, or three-level meta-atoms in meta-materials.

  13. Nestor optical modules blackening

    International Nuclear Information System (INIS)

    Cordelli, M.; Rutili, A.; Trasatti, L.

    1998-09-01

    The optical modules (OM) containing the photomultiplier tubes (PM) for a deep sea neutrino telescope must be protected them from direct sunlight. The problem has been solved using a heat shrink plastic sheet with very good optical and mechanical properties

  14. Programmable synchronous communications module

    International Nuclear Information System (INIS)

    Horelick, D.

    1979-10-01

    The functional characteristics of a programmable, synchronous serial communications CAMAC module with buffering in block format are described. Both bit and byte oriented protocols can be handled in full duplex depending on the program implemented. The main elements of the module are a Signetics 2652 Multi-Protocol Communications Controller, a Zilog Z-808 8 bit microprocessor with PROM and RAM, and FIFOs for buffering

  15. Groups, rings, modules

    CERN Document Server

    Auslander, Maurice

    2014-01-01

    This classic monograph is geared toward advanced undergraduates and graduate students. The treatment presupposes some familiarity with sets, groups, rings, and vector spaces. The four-part approach begins with examinations of sets and maps, monoids and groups, categories, and rings. The second part explores unique factorization domains, general module theory, semisimple rings and modules, and Artinian rings. Part three's topics include localization and tensor products, principal ideal domains, and applications of fundamental theorem. The fourth and final part covers algebraic field extensions

  16. Modulated Current Drive Measurements

    International Nuclear Information System (INIS)

    Petty, C.C.; Lohr, J.; Luce, T.C.; Prater, R.; Cox, W.A.; Forest, C.B.; Jayakumar, R.J.; Makowski, M.A.

    2005-01-01

    A new measurement approach is presented which directly determines the noninductive current profile from the periodic response of the motional Stark effect (MSE) signals to the slow modulation of the external current drive source. A Fourier transform of the poloidal magnetic flux diffusion equation is used to analyze the MSE data. An example of this measurement technique is shown using modulated electron cyclotron current drive (ECCD) discharges from the DIII-D tokamak

  17. Directed network modules

    International Nuclear Information System (INIS)

    Palla, Gergely; Farkas, Illes J; Pollner, Peter; Derenyi, Imre; Vicsek, Tamas

    2007-01-01

    A search technique locating network modules, i.e. internally densely connected groups of nodes in directed networks is introduced by extending the clique percolation method originally proposed for undirected networks. After giving a suitable definition for directed modules we investigate their percolation transition in the Erdos-Renyi graph both analytically and numerically. We also analyse four real-world directed networks, including Google's own web-pages, an email network, a word association graph and the transcriptional regulatory network of the yeast Saccharomyces cerevisiae. The obtained directed modules are validated by additional information available for the nodes. We find that directed modules of real-world graphs inherently overlap and the investigated networks can be classified into two major groups in terms of the overlaps between the modules. Accordingly, in the word-association network and Google's web-pages, overlaps are likely to contain in-hubs, whereas the modules in the email and transcriptional regulatory network tend to overlap via out-hubs

  18. Second generation SLAC modulator

    International Nuclear Information System (INIS)

    Donaldson, A.R.; Cron, J.C.; Hanselman, R.R.

    1986-06-01

    The Stanford Linear Accelerator Laboratory has undertaken the construction of a single pass electron-positron collider. In order to reach required beam energy 235 new klystrons needed upgraded modulator systems. The collider will use 50 GeV electrons and positrons. The increase in accelerator energy from the present 30 GeV necessitates the replacement of existing 35 MW klystrons with new 67 MW units. The doubling of klystron output power required a redesign of the modulator system. The 67 MW klystron needs a 350 kV beam voltage pulse with a 3.7 μs pulse width. A new pulse transformer was designed to deliver the increased voltage and pulse width. Pulse cable design was evaluated to obtain increased reliability of that critical element. The modulator, with the exception of its power supply, was rebuilt to produce the required power increase while enhancing reliability and improving maintainability. An investigation of present thyratron switch tube performance under the new operating conditions resulted in agitation and some warranted panic but these conditions were mitigated after several successful experiments and some evolutionary narrowing of the klystron pulse width. The discussion will cover the upgraded modulator system specifications and some details of the new pulse transformer tank, pulse cable, modulator, and modulator switch tube

  19. Decoupled Modulation Control

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Shaobu; Huang, Renke; Huang, Zhenyu; Diao, Ruisheng

    2016-06-03

    The objective of this research work is to develop decoupled modulation control methods for damping inter-area oscillations with low frequencies, so the damping control can be more effective and easier to design with less interference among different oscillation modes in the power system. A signal-decoupling algorithm was developed that can enable separation of multiple oscillation frequency contents and extraction of a “pure” oscillation frequency mode that are fed into Power System Stabilizers (PSSs) as the modulation input signals. As a result, instead of introducing interferences between different oscillation modes from the traditional approaches, the output of the new PSS modulation control signal mainly affects only one oscillation mode of interest. The new decoupled modulation damping control algorithm has been successfully developed and tested on the standard IEEE 4-machine 2-area test system and a minniWECC system. The results are compared against traditional modulation controls, which demonstrates the validity and effectiveness of the newly-developed decoupled modulation damping control algorithm.

  20. Superstability for Generalized Module Left Derivations and Generalized Module Derivations on a Banach Module (I

    Directory of Open Access Journals (Sweden)

    Rassias JM

    2009-01-01

    Full Text Available We discuss the superstability of generalized module left derivations and generalized module derivations on a Banach module. Let be a Banach algebra and a Banach -module, and . The mappings , and are defined and it is proved that if (resp., is dominated by then is a generalized (resp., linear module- left derivation and is a (resp., linear module- left derivation. It is also shown that if (resp., is dominated by then is a generalized (resp., linear module- derivation and is a (resp., linear module- derivation.

  1. Pulse power modulators - an overview

    International Nuclear Information System (INIS)

    Venkatramani, N.

    2006-01-01

    Pulse power modulators are electronic devices to provide, high voltage, high current, power bursts. Ideally, a modulator, with the means to shape and control the pulses, acts as a switch between a high voltage power supply and its load. This article gives an overview of the pulse power modulators: starting with the basics of pulse and modulation, it covers modulation topologies, different types of modulators, major subsystems and pulse measurement techniques. The various applications of pulse power modulators and the recent trends have been included at the end. (author)

  2. Phase ramping and modulation of reflectometer signals

    International Nuclear Information System (INIS)

    Conway, G.D.; Bartlett, D.V.; Stoff, P.E.

    1999-01-01

    The phase and amplitude signals of JET heterodyne reflectometers show varying levels of high frequency turbulence superimposed on a slow changing mean. The phase signal also shows multi-radian (> 1 fringe) variations with two quite different time scales (2-10 ms and sub-ms). In both cases the mean reflected power, together with turbulent phase and amplitude fluctuation levels, are modulated synchronously with the are modulated synchronously with the phase fringes. The slow fringes appear to result radial movement of the cutoff layer with the amplitude modulation possibly due to multiple reflection between plasma and wall. The fast fringes occur in intermittent bursts and appear to be phase runaway resulting from antenna misalignment. Using a 2-D physical optics simulation code it is possible to replicate the fast bursts of phase runaway from steady-state turbulence and misaligned antennas. This offers a possible alternative explanation for some of the observations of bursting turbulence seen in reflectometer signals. (authors)

  3. Spatial Terahertz Modulator

    Science.gov (United States)

    Xie, Zhenwei; Wang, Xinke; Ye, Jiasheng; Feng, Shengfei; Sun, Wenfeng; Akalin, Tahsin; Zhang, Yan

    2013-11-01

    Terahertz (THz) technology is a developing and promising candidate for biological imaging, security inspection and communications, due to the low photon energy, the high transparency and the broad band properties of the THz radiation. However, a major encountered bottleneck is lack of efficient devices to manipulate the THz wave, especially to modulate the THz wave front. A wave front modulator should allow the optical or electrical control of the spatial transmission (or reflection) of an input THz wave and hence the ability to encode the information in a wave front. Here we propose a spatial THz modulator (STM) to dynamically control the THz wave front with photo-generated carriers. A computer generated THz hologram is projected onto a silicon wafer by a conventional spatial light modulator (SLM). The corresponding photo-generated carrier spatial distribution will be induced, which forms an amplitude hologram to modulate the wave front of the input THz beam. Some special intensity patterns and vortex beams are generated by using this method. This all-optical controllable STM is structure free, high resolution and broadband. It is expected to be widely used in future THz imaging and communication systems.

  4. Bunch identification module

    International Nuclear Information System (INIS)

    Fox, J.D.

    1981-01-01

    This module provides bunch identification and timing signals for the PEP Interaction areas. Timing information is referenced to the PEP master oscillator, and adjusted in phase as a function of region. Identification signals are generated in a manner that allows observers in all interaction regions to agree on an unambiguous bunch identity. The module provides bunch identification signals via NIM level logic, upon CAMAC command, and through LED indicators. A front panel ''region select'' switch allows the same module to be used in all regions. The module has two modes of operation: a bunch identification mode and a calibration mode. In the identification mode, signals indicate which of the three bunches of electrons and positrons are interacting, and timing information about beam crossing is provided. The calibration mode is provided to assist experimenters making time of flight measurements. In the calibration mode, three distinct gating signals are referenced to a selected bunch, allowing three timing systems to be calibrated against a common standard. Physically, the bunch identifier is constructed as a single width CAMAC module. 2 figs., 1 tab

  5. Integrated unaligned resonant modulator tuning

    Energy Technology Data Exchange (ETDEWEB)

    Zortman, William A.; Lentine, Anthony L.

    2017-10-03

    Methods and systems for tuning a resonant modulator are disclosed. One method includes receiving a carrier signal modulated by the resonant modulator with a stream of data having an approximately equal number of high and low bits, determining an average power of the modulated carrier signal, comparing the average power to a predetermined threshold, and operating a tuning device coupled to the resonant modulator based on the comparison of the average power and the predetermined threshold. One system includes an input structure, a plurality of processing elements, and a digital control element. The input structure is configured to receive, from the resonant modulator, a modulated carrier signal. The plurality of processing elements are configured to determine an average power of the modulated carrier signal. The digital control element is configured to operate a tuning device coupled to the resonant modulator based on the average power of the modulated carrier signal.

  6. Power module assembly

    Science.gov (United States)

    Campbell, Jeremy B [Torrance, CA; Newson, Steve [Redondo Beach, CA

    2011-11-15

    A power module assembly of the type suitable for deployment in a vehicular power inverter, wherein the power inverter has a grounded chassis, is provided. The power module assembly comprises a conductive base layer electrically coupled to the chassis, an insulating layer disposed on the conductive base layer, a first conductive node disposed on the insulating layer, a second conductive node disposed on the insulating layer, wherein the first and second conductive nodes are electrically isolated from each other. The power module assembly also comprises a first capacitor having a first electrode electrically connected to the conductive base layer, and a second electrode electrically connected to the first conductive node, and further comprises a second capacitor having a first electrode electrically connected to the conductive base layer, and a second electrode electrically connected to the second conductive node.

  7. Waveform Sampler CAMAC Module

    International Nuclear Information System (INIS)

    Freytag, D.R.; Haller, G.M.; Kang, H.; Wang, J.

    1985-09-01

    A Waveform Sampler Module (WSM) for the measurement of signal shapes coming from the multi-hit drift chambers of the SLAC SLC detector is described. The module uses a high speed, high resolution analog storage device (AMU) developed in collaboration between SLAC and Stanford University. The AMU devices together with high speed TTL clocking circuitry are packaged in a hybrid which is also suitable for mounting on the detector. The module is in CAMAC format and provides eight signal channels, each recording signal amplitude versus time in 512 cells at a sampling rate of up to 360 MHz. Data are digitized by a 12-bit ADC with a 1 μs conversion time and stored in an on-board memory accessible through CAMAC

  8. GREET Pretreatment Module

    Energy Technology Data Exchange (ETDEWEB)

    Adom, Felix K. [Argonne National Lab. (ANL), Argonne, IL (United States). Energy Systems Division; Dunn, Jennifer B. [Argonne National Lab. (ANL), Argonne, IL (United States). Energy Systems Division; Han, Jeongwoo [Argonne National Lab. (ANL), Argonne, IL (United States). Energy Systems Division

    2014-09-01

    A wide range of biofuels and biochemicals can be produced from cellulosic biomass via different pretreatment technologies that yield sugars. Process simulations of dilute acid and ammonia fiber expansion pretreatment processes and subsequent hydrolysis were developed in Aspen Plus for four lignocellulosic feedstocks (corn stover, miscanthus, switchgrass, and poplar). This processing yields sugars that can be subsequently converted to biofuels or biochemical. Material and energy consumption data from Aspen Plus were then compiled in a new Greenhouses Gases, Regulated Emissions, and Energy Use in Transportation (GREETTM) pretreatment module. The module estimates the cradle-to-gate fossil energy consumption (FEC) and greenhouse gas (GHG) emissions associated with producing fermentable sugars. This report documents the data and methodology used to develop this module and the cradle-to-gate FEC and GHG emissions that result from producing fermentable sugars.

  9. Space Experiment Module (SEM)

    Science.gov (United States)

    Brodell, Charles L.

    1999-01-01

    The Space Experiment Module (SEM) Program is an education initiative sponsored by the National Aeronautics and Space Administration (NASA) Shuttle Small Payloads Project. The program provides nationwide educational access to space for Kindergarten through University level students. The SEM program focuses on the science of zero-gravity and microgravity. Within the program, NASA provides small containers or "modules" for students to fly experiments on the Space Shuttle. The experiments are created, designed, built, and implemented by students with teacher and/or mentor guidance. Student experiment modules are flown in a "carrier" which resides in the cargo bay of the Space Shuttle. The carrier supplies power to, and the means to control and collect data from each experiment.

  10. CAMAC system test module

    International Nuclear Information System (INIS)

    Dawson, W.K.; Gjovig, A.; Naivar, F.; Potter, J.; Smith, W.

    1981-01-01

    Since the CAMAC Branch Highway is used to both send information to and receive information from a CAMAC crate, faults in this highway can be difficult to recognize and diagnose. Similarly faults caused by a Crate Controller corrupting either instructions or data are difficult to distinguish from faults caused by the modules themselves. The CLIVIT (CAMAC Logic Integrity Via Interactive Testing) module is designed to largely eliminate such difficulties and ambiguities by allowing the verification of Branch Highway and Dataway transactions via an independent data communication path. The principle of operation of the CLIVIT is explained. Described are the prototype construction, testing and use

  11. Instant node package module

    CERN Document Server

    Ali, Juzer

    2013-01-01

    Get to grips with a new technology, understand what it is and what it can do for you, and then get to work with the most important features and tasks. A practical exploration of the lifecycle of creating node modules as well as learning all of the top features that npm has to offer.Intended for readers who want to create their first node.js modules. The programming paradigm of JavaScript is not covered so a foundation in these concepts would be beneficial.

  12. Flexible programmable logic module

    Science.gov (United States)

    Robertson, Perry J.; Hutchinson, Robert L.; Pierson, Lyndon G.

    2001-01-01

    The circuit module of this invention is a VME board containing a plurality of programmable logic devices (PLDs), a controlled impedance clock tree, and interconnecting buses. The PLDs are arranged to permit systolic processing of a problem by offering wide data buses and a plurality of processing nodes. The board contains a clock reference and clock distribution tree that can drive each of the PLDs with two critically timed clock references. External clock references can be used to drive additional circuit modules all operating from the same synchronous clock reference.

  13. Photovoltaic module and interlocked stack of photovoltaic modules

    Science.gov (United States)

    Wares, Brian S.

    2012-09-04

    One embodiment relates to an arrangement of photovoltaic modules configured for transportation. The arrangement includes a plurality of photovoltaic modules, each photovoltaic module including a frame having at least a top member and a bottom member. A plurality of alignment features are included on the top member of each frame, and a plurality of alignment features are included on the bottom member of each frame. Adjacent photovoltaic modules are interlocked by the alignment features on the top member of a lower module fitting together with the alignment features on the bottom member of an upper module. Other embodiments, features and aspects are also disclosed.

  14. Annexin A2 and cancer

    DEFF Research Database (Denmark)

    Christensen, Maria V; Høgdall, Claus K; Jochumsen, Kirsten M

    2018-01-01

    Annexin A2 is a 36-kDa protein interfering with multiple cellular processes especially in cancer progression. The present review aimed to show the relations between Annexin A2 and cancer. A systematic search for studies investigating cancer and Annexin A2 expression was conducted using Pub......Med. Acute lymphoblastic leukaemia, acute promyelocytic leukaemia, clear cell renal cell carcinoma, breast, cervical, colorectal, endometrial, gastric cancer, glioblastoma, hepatocellular carcinoma, lung, multiple myeloma, oesophageal squamous cell carcinoma, ovarian cancer, pancreatic duct adenocarcinoma......, prostate cancer and urothelial carcinoma were evaluated. Annexin A2 expression correlates with resistance to treatment, binding to the bone marrow, histological grade and type, TNM-stage and shortened overall survival. The regulation of Annexin A2 is of interest due to its potential as target for a more...

  15. Modelling the Photovoltaic Module

    DEFF Research Database (Denmark)

    Katsanevakis, Markos

    2011-01-01

    This paper refers into various ways in simulation the Photovoltaic (PV) module behaviour under any combination of solar irradiation and ambient temperature. There are three different approaches presented here briefly and one of them is chosen because of its good accuracy and relatively low...

  16. Special Attachments. Module 19.

    Science.gov (United States)

    South Carolina State Dept. of Education, Columbia. Office of Vocational Education.

    This module on special attachments, one in a series dealing with industrial sewing machines, their attachments, and operation, covers four topics: gauges; cording attachment; zipper foot; and hemming, shirring, and binding. For each topic these components are provided: an introduction, directions, an objective, learning activities, student…

  17. Special Operation. Module 20.

    Science.gov (United States)

    South Carolina State Dept. of Education, Columbia. Office of Vocational Education.

    This module on special operations, one in a series dealing with industrial sewing machines, their attachments, and operation, covers two topics: topstitching and mitering. For each topic these components are provided: an introduction, directions, an objective, learning activities, student information, a student self-check, and a check-out…

  18. Barrel Module0 Autopsy

    CERN Document Server

    Cobal, M; Nessi, Marzio; Blanch, O; Zamora, Y

    1999-01-01

    Using the information from the Cs calibration runs, many of the problems affecting the response of the barrel Module0 prototype have been spotted out. These can be bad fibre-tile couplings, light losses from fibres bundling, broken fibres, not transparent tiles etc. After a visual inspection, most of these problems have been repaired.

  19. Rescue Manual. Module 6.

    Science.gov (United States)

    Ohio State Univ., Columbus. Instructional Materials Lab.

    This learner manual for rescuers covers the current techniques or practices required in the rescue service. The sixth of 10 modules contains 4 chapters: (1) industrial rescue; (2) rescue from a confined space; (3) extrication from heavy equipment; and (4) rescue operations involving elevators. Key points, an introduction, and conclusion accompany…

  20. Evolutionary and developmental modules.

    Science.gov (United States)

    Lacquaniti, Francesco; Ivanenko, Yuri P; d'Avella, Andrea; Zelik, Karl E; Zago, Myrka

    2013-01-01

    The identification of biological modules at the systems level often follows top-down decomposition of a task goal, or bottom-up decomposition of multidimensional data arrays into basic elements or patterns representing shared features. These approaches traditionally have been applied to mature, fully developed systems. Here we review some results from two other perspectives on modularity, namely the developmental and evolutionary perspective. There is growing evidence that modular units of development were highly preserved and recombined during evolution. We first consider a few examples of modules well identifiable from morphology. Next we consider the more difficult issue of identifying functional developmental modules. We dwell especially on modular control of locomotion to argue that the building blocks used to construct different locomotor behaviors are similar across several animal species, presumably related to ancestral neural networks of command. A recurrent theme from comparative studies is that the developmental addition of new premotor modules underlies the postnatal acquisition and refinement of several different motor behaviors in vertebrates.

  1. Paratransit: An Instructional Module.

    Science.gov (United States)

    Scalici, Anthony

    A concept-based introduction to paratransit is provided in this instructional module for undergraduate and graduate transportation-related courses for disciplines such as engineering, business, marketing, and technology. The concept of paratransit generally refers to modes of transportation other than mass transit and solo-driven automobiles. The…

  2. Morusinol extracted from Morus alba inhibits arterial thrombosis and modulates platelet activation for the treatment of cardiovascular disease.

    Science.gov (United States)

    Lee, Jung-Jin; Yang, Hyun; Yoo, Yeong-Min; Hong, Seong Su; Lee, Dongho; Lee, Hyun-Jung; Lee, Hak-Ju; Myung, Chang-Seon; Choi, Kyung-Chul; Jeung, Eui-Bae

    2012-01-01

    Morus alba (white mulberry) has been used in traditional Chinese medicine as an anti-headache, diuretic, expectorant, and anti-diabetic agent. In previous studies, extracts of Morus alba demonstrated favorable biological properties, such as antioxidant activity, suppression of lipoxygenase (LOX)-1, cytotoxicity against cancer cells, and inhibition of the invasion and migration of cancer cells. This study further evaluated the effects of morusinol, a flavonoid derived from Morus alba root bark, on platelet aggregation and thromboxane B(2) (TXB(2) formation in vitro and thrombus formation in vivo. The antiplatelet potential of morusinol was measured using in vitro rabbit platelet aggregation and TXB(2) formation assays. Arterial thrombus formation was investigated using an in vivo ferric chloride (FeCl(3)-induced thrombosis model. Morusinol significantly inhibited collagen- and arachidonic acid-induced platelet aggregation and TXB(2) formation in cultured platelets in a concentration-dependent manner. Thrombus formation was reduced by 32.1, 42.0, and 99.0% for collagen-induced TXB(2) formation, and 8.0, 24.1, and 29.2% for arachadonic acid-induced TXB(2) formation, with 5, 10, and 30 µg/mL morusinol, respectively. Moreover, oral morusinol (20 mg/kg) or aspirin (20 mg/kg) for three days significantly increased the time to occlusion in vivo by 20.3±5.0 or 6.8±2.9 min, respectively, compared with the control (1% CMC, carboxymethyl cellulose). Taken together, these results indicate that morusinol may significantly inhibit arterial thrombosis in vivo due to antiplatelet activity. Thus, morusinol may exert beneficial effects on transient ischemic attacks or stroke via the modulation of platelet activation.

  3. Modulation of platelet aggregation by areca nut and betel leaf ingredients: roles of reactive oxygen species and cyclooxygenase.

    Science.gov (United States)

    Jeng, Jiiang-Huei; Chen, Shiao-Yun; Liao, Chang-Hui; Tung, Yuan-Yii; Lin, Bor-Ru; Hahn, Liang-Jiunn; Chang, Mei-Chi

    2002-05-01

    There are 2 to 6 billion betel quid (BQ) chewers in the world. Areca nut (AN), a BQ component, modulates arachidonic acid (AA) metabolism, which is crucial for platelet function. AN extract (1 and 2 mg/ml) stimulated rabbit platelet aggregation, with induction of thromboxane B2 (TXB2) production. Contrastingly, Piper betle leaf (PBL) extract inhibited AA-, collagen-, and U46619-induced platelet aggregation, and TXB2 and prostaglandin-D2 (PGD2) production. PBL extract also inhibited platelet TXB2 and PGD2 production triggered by thrombin, platelet activating factor (PAF), and adenosine diphosphate (ADP), whereas little effect on platelet aggregation was noted. Moreover, PBL is a scavenger of O2(*-) and *OH, and inhibits xanthine oxidase activity and the (*)OH-induced PUC18 DNA breaks. Deferoxamine, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) and neomycin prevented AN-induced platelet aggregation and TXB2 production. Indomethacin, genistein, and PBL extract inhibited only TXB2 production, but not platelet aggregation. Catalase, superoxide dismutase, and dimethylthiourea (DMT) showed little effect on AN-induced platelet aggregation, whereas catalase and DMT inhibited the AN-induced TXB2 production. These results suggest that AN-induced platelet aggregation is associated with iron-mediated reactive oxygen species production, calcium mobilization, phospholipase C activation, and TXB2 production. PBL inhibited platelet aggregation via both its antioxidative effects and effects on TXB2 and PGD2 production. Effects of AN and PBL on platelet aggregation and AA metabolism is crucial for platelet activation in the oral mucosa and cardiovascular system in BQ chewers.

  4. Young module multiplicities and classifying the indecomposable Young permutation modules

    OpenAIRE

    Gill, Christopher C.

    2012-01-01

    We study the multiplicities of Young modules as direct summands of permutation modules on cosets of Young subgroups. Such multiplicities have become known as the p-Kostka numbers. We classify the indecomposable Young permutation modules, and, applying the Brauer construction for p-permutation modules, we give some new reductions for p-Kostka numbers. In particular we prove that p-Kostka numbers are preserved under multiplying partitions by p, and strengthen a known reduction given by Henke, c...

  5. A 2:1 MUX Based on Multiple MEMS Resonators

    KAUST Repository

    Hafiz, Md Abdullah Al

    2017-01-09

    Micro/nano-electromechanical resonator based mechanical computing has recently attracted significant attention. This paper reports a realization of a 2:1 MUX, a concatenable digital logic element, based on electrothermal frequency tuning of electrically connected multiple arch resonators. Toward this, shallow arch shaped microresonators are electrically connected and their resonance frequencies are tuned based on an electrothermal frequency modulation scheme. This study demonstrates that by reconfiguring the same basic building block, the arch microresonator, complex logic circuits can be realized.

  6. A 2:1 MUX Based on Multiple MEMS Resonators

    KAUST Repository

    Hafiz, Md Abdullah Al; Kosuru, Lakshmoji; Younis, Mohammad I.; Fariborzi, Hossein

    2017-01-01

    Micro/nano-electromechanical resonator based mechanical computing has recently attracted significant attention. This paper reports a realization of a 2:1 MUX, a concatenable digital logic element, based on electrothermal frequency tuning of electrically connected multiple arch resonators. Toward this, shallow arch shaped microresonators are electrically connected and their resonance frequencies are tuned based on an electrothermal frequency modulation scheme. This study demonstrates that by reconfiguring the same basic building block, the arch microresonator, complex logic circuits can be realized.

  7. Modulating aging and longevity

    DEFF Research Database (Denmark)

    Rattan, Suresh

    Provides information and an evaluation of a variety of approaches tried for modulating aging and longevity, including dietary supplementation with antioxidants, vitamins and hormones, genetic engineering, life-style alterations, and hormesis through mild stress. After decades of systematic collec....... The goal of research on ageing is not to increase human longevity regardless of the consequences, but to increase active longevity free from disability and functional dependence......Provides information and an evaluation of a variety of approaches tried for modulating aging and longevity, including dietary supplementation with antioxidants, vitamins and hormones, genetic engineering, life-style alterations, and hormesis through mild stress. After decades of systematic...... collection of data describing age-related changes in organisms, organs, tissues, cells and macromolecules, biogerontologists are now in a position to construct general principles of ageing and explore various possibilities of intervention using rational approaches. While not giving serious consideration...

  8. Weighted network modules

    International Nuclear Information System (INIS)

    Farkas, Illes; Abel, Daniel; Palla, Gergely; Vicsek, Tamas

    2007-01-01

    The inclusion of link weights into the analysis of network properties allows a deeper insight into the (often overlapping) modular structure of real-world webs. We introduce a clustering algorithm clique percolation method with weights (CPMw) for weighted networks based on the concept of percolating k-cliques with high enough intensity. The algorithm allows overlaps between the modules. First, we give detailed analytical and numerical results about the critical point of weighted k-clique percolation on (weighted) Erdos-Renyi graphs. Then, for a scientist collaboration web and a stock correlation graph we compute three-link weight correlations and with the CPMw the weighted modules. After reshuffling link weights in both networks and computing the same quantities for the randomized control graphs as well, we show that groups of three or more strong links prefer to cluster together in both original graphs

  9. Quad nanosecond delay module

    International Nuclear Information System (INIS)

    McDonald, R.J.; Hunter, J.B.; Wozniak, G.J.

    1986-04-01

    Four nanosecond (ns) delay units have been designed to fit in a single-width NIM module. This module is particularly suited for use in conjunction with quad constant fraction timing discriminators (CFTDs) since it has four delay units that can be placed adjacent to the four units of the CFTD. A series of different length cables connected via DIP toggle switches provide delays of 0.60 ns in 4 ns increments. Thus, the CFTD delay can be optimized for pulses of different rise times from approx.10-100 ns. Design work for the PC board and silkscreening of the front panel were done with the MacDraw program on the Apple Mackintosh computer and printed with the Lasewriter printer. 6 refs

  10. Silicon Optical Modulator Simulation

    Directory of Open Access Journals (Sweden)

    Soon Thor LIM

    2015-04-01

    Full Text Available We developed a way of predicting and analyzing high speed optical modulator. Our research adopted a bottom-up approach to consider high-speed optical links using an eye diagram. Our method leverages on modular mapping of electrical characteristics to optical characteristics, while attaining the required accuracy necessary for device footprint approaching sub-micron scales where electrical data distribution varies drastically. We calculate for the bias dependent phase shift (2pi/mm and loss (dB/mm for the optical modulator based on the real and imaginary part of complex effective indices. Subsequently, combine effectively both the electrical and optical profiles to construct the optical eye diagram which is the essential gist of signal integrity of such devices.

  11. Glucocorticoid receptor modulators.

    Science.gov (United States)

    Meijer, Onno C; Koorneef, Lisa L; Kroon, Jan

    2018-06-01

    The glucocorticoid hormone cortisol acts throughout the body to support circadian processes and adaptation to stress. The glucocorticoid receptor is the target of cortisol and of synthetic glucocorticoids, which are used widely in the clinic. Both agonism and antagonism of the glucocorticoid receptor may be beneficial in disease, but given the wide expression of the receptor and involvement in various processes, beneficial effects are often accompanied by unwanted side effects. Selective glucocorticoid receptor modulators are ligands that induce a receptor conformation that allows activation of only a subset of downstream signaling pathways. Such molecules thereby combine agonistic and antagonistic properties. Here we discuss the mechanisms underlying selective receptor modulation and their promise in treating diseases in several organ systems where cortisol signaling plays a role. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  12. Investigating Quantum Modulation States

    Science.gov (United States)

    2016-03-01

    Coherent state quantum data encryption is highly interoperable with current classical optical infrastructure in both fiber and free space optical networks...hub’s field of regard has a transmit/receive module that are endpoints of the Lyot filter stage tree within the hub’s backend electro-optics control... mobile airborne and space-borne networking. Just like any laser communication technology, QC links are affected by several sources of distortions

  13. Sparx PCA Module

    Energy Technology Data Exchange (ETDEWEB)

    2017-04-25

    Sparx, a new environment for Cryo-EM image processing; Cryo-EM, Single particle reconstruction, principal component analysis; Hardware Req.: PC, MAC, Supercomputer, Mainframe, Multiplatform, Workstation. Software Req.: operating system is Unix; Compiler C++; type of files: source code, object library, executable modules, compilation instructions; sample problem input data. Location/transmission: http://sparx-em.org; User manual & paper: http://sparx-em.org;

  14. Modulated Pade approximant

    International Nuclear Information System (INIS)

    Ginsburg, C.A.

    1980-01-01

    In many problems, a desired property A of a function f(x) is determined by the behaviour of f(x) approximately equal to g(x,A) as x→xsup(*). In this letter, a method for resuming the power series in x of f(x) and approximating A (modulated Pade approximant) is presented. This new approximant is an extension of a resumation method for f(x) in terms of rational functions. (author)

  15. of Banach modules

    Directory of Open Access Journals (Sweden)

    Anousheh Fatemeh

    2015-10-01

    Full Text Available Let A be a Banach algebra, E be a Banach A-bimodule and Δ E → A be a bounded Banach A-bimodule homomorphism. It is shown that under some mild conditions, the weakΔ''-amenability of E'' (as an A''-bimodule necessitates weak Δ-amenability of E (as an A-bimodule. Some examples of weak-amenable Banach modules are provided as well.

  16. FERMI multi-chip module

    CERN Multimedia

    This FERMI multi-chip module contains five million transistors. 25 000 of these modules will handle the flood of information through parts of the ATLAS and CMS detectors at the LHC. To select interesting events for recording, crucial decisions are taken before the data leaves the detector. FERMI modules are being developed at CERN in partnership with European industry.

  17. Receiver Gain Modulation Circuit

    Science.gov (United States)

    Jones, Hollis; Racette, Paul; Walker, David; Gu, Dazhen

    2011-01-01

    A receiver gain modulation circuit (RGMC) was developed that modulates the power gain of the output of a radiometer receiver with a test signal. As the radiometer receiver switches between calibration noise references, the test signal is mixed with the calibrated noise and thus produces an ensemble set of measurements from which ensemble statistical analysis can be used to extract statistical information about the test signal. The RGMC is an enabling technology of the ensemble detector. As a key component for achieving ensemble detection and analysis, the RGMC has broad aeronautical and space applications. The RGMC can be used to test and develop new calibration algorithms, for example, to detect gain anomalies, and/or correct for slow drifts that affect climate-quality measurements over an accelerated time scale. A generalized approach to analyzing radiometer system designs yields a mathematical treatment of noise reference measurements in calibration algorithms. By treating the measurements from the different noise references as ensemble samples of the receiver state, i.e. receiver gain, a quantitative description of the non-stationary properties of the underlying receiver fluctuations can be derived. Excellent agreement has been obtained between model calculations and radiometric measurements. The mathematical formulation is equivalent to modulating the gain of a stable receiver with an externally generated signal and is the basis for ensemble detection and analysis (EDA). The concept of generating ensemble data sets using an ensemble detector is similar to the ensemble data sets generated as part of ensemble empirical mode decomposition (EEMD) with exception of a key distinguishing factor. EEMD adds noise to the signal under study whereas EDA mixes the signal with calibrated noise. It is mixing with calibrated noise that permits the measurement of temporal-functional variability of uncertainty in the underlying process. The RGMC permits the evaluation of EDA by

  18. Bent Electro-Absorption Modulator

    DEFF Research Database (Denmark)

    2002-01-01

    by applying a variable electric or electronmagnetic field. The modulation of the complex refractive index results in a modulation of the refractive index contrast and the absorption coefficient for the waveguide at the frequency of the light. By carefully adjusting the composition of the semiconducting...... components and the applied electric field in relation to the frequency of the modulated radiation, the bending losses (and possibly coupling losses) will provide extinction of light guided by the bent waveguide section. The refractive index contract may be modulated while keeping the absorption coefficient......The present invention relates to a method and a device for modulating optical signals based on modulating bending losses in bend, quantum well semiconductor waveguide sections. The complex refractive index of the optical active semiconducting components of the waveguide section is modulated...

  19. On staggered indecomposable Virasoro modules

    International Nuclear Information System (INIS)

    Kytoelae, Kalle; Ridout, David

    2009-01-01

    In this article, certain indecomposable Virasoro modules are studied. Specifically, the Virasoro mode L 0 is assumed to be nondiagonalizable, possessing Jordan blocks of rank 2. Moreover, the module is further assumed to have a highest weight submodule, the 'left module', and that the quotient by this submodule yields another highest weight module, the 'right module'. Such modules, which have been called staggered, have appeared repeatedly in the logarithmic conformal field theory literature, but their theory has not been explored in full generality. Here, such a theory is developed for the Virasoro algebra using rather elementary techniques. The focus centers on two different but related questions typically encountered in practical studies: How can one identify a given staggered module, and how can one demonstrate the existence of a proposed staggered module. Given just the values of the highest weights of the left and right modules, themselves subject to simple necessary conditions, invariants are defined which together with the knowledge of the left and right modules uniquely identify a staggered module. The possible values of these invariants form a vector space of dimension 0, 1, or 2, and the structures of the left and right modules limit the isomorphism classes of the corresponding staggered modules to an affine subspace (possibly empty). The number of invariants and affine restrictions is purely determined by the structures of the left and right modules. Moreover, in order to facilitate applications, the expressions for the invariants and restrictions are given by formulas as explicit as possible (they generally rely on expressions for Virasoro singular vectors). Finally, the text is liberally peppered throughout with examples illustrating the general concepts. These have been carefully chosen for their physical relevance or for the novel features they exhibit.

  20. On staggered indecomposable Virasoro modules

    Energy Technology Data Exchange (ETDEWEB)

    Kytoelae, Kalle [Geneve Univ. (Switzerland); Ridout, David [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

    2009-06-15

    In this article, certain indecomposable Virasoro modules are studied. Specifically, the Virasoro mode L0 is assumed to be non-diagonalisable, possessing Jordan blocks of rank two. Moreover, the module is further assumed to have a highest weight submodule, the ''left module'', and that the quotient by this submodule yields another highest weight module, the ''right module''. Such modules, which have been called staggered, have appeared repeatedly in the logarithmic conformal field theory literature, but their theory has not been explored in full generality. Here, such a theory is developed for the Virasoro algebra using rather elementary techniques. The focus centres on two different but related questions typically encountered in practical studies: How can one identify a given staggered module, and how can one demonstrate the existence of a proposed staggered module. Given just the values of the highest weights of the left and right modules, themselves subject to simple necessary conditions, invariants are defined which together with the knowledge of the left and right modules uniquely identify a staggered module. The possible values of these invariants form a vector space of dimension zero, one or two, and the structures of the left and right modules limit the isomorphism classes of the corresponding staggered modules to an affine subspace (possibly empty). The number of invariants and affine restrictions is purely determined by the structures of the left and right modules. Moreover, in order to facilitate applications, the expressions for the invariants and restrictions are given by formulae as explicit as possible (they generally rely on expressions for Virasoro singular vectors). Finally, the text is liberally peppered throughout with examples illustrating the general concepts. These have been carefully chosen for their physical relevance or for the novel features they exhibit. (orig.)

  1. On staggered indecomposable Virasoro modules

    International Nuclear Information System (INIS)

    Kytoelae, Kalle; Ridout, David

    2009-06-01

    In this article, certain indecomposable Virasoro modules are studied. Specifically, the Virasoro mode L0 is assumed to be non-diagonalisable, possessing Jordan blocks of rank two. Moreover, the module is further assumed to have a highest weight submodule, the ''left module'', and that the quotient by this submodule yields another highest weight module, the ''right module''. Such modules, which have been called staggered, have appeared repeatedly in the logarithmic conformal field theory literature, but their theory has not been explored in full generality. Here, such a theory is developed for the Virasoro algebra using rather elementary techniques. The focus centres on two different but related questions typically encountered in practical studies: How can one identify a given staggered module, and how can one demonstrate the existence of a proposed staggered module. Given just the values of the highest weights of the left and right modules, themselves subject to simple necessary conditions, invariants are defined which together with the knowledge of the left and right modules uniquely identify a staggered module. The possible values of these invariants form a vector space of dimension zero, one or two, and the structures of the left and right modules limit the isomorphism classes of the corresponding staggered modules to an affine subspace (possibly empty). The number of invariants and affine restrictions is purely determined by the structures of the left and right modules. Moreover, in order to facilitate applications, the expressions for the invariants and restrictions are given by formulae as explicit as possible (they generally rely on expressions for Virasoro singular vectors). Finally, the text is liberally peppered throughout with examples illustrating the general concepts. These have been carefully chosen for their physical relevance or for the novel features they exhibit. (orig.)

  2. On staggered indecomposable Virasoro modules

    Science.gov (United States)

    Kytölä, Kalle; Ridout, David

    2009-12-01

    In this article, certain indecomposable Virasoro modules are studied. Specifically, the Virasoro mode L0 is assumed to be nondiagonalizable, possessing Jordan blocks of rank 2. Moreover, the module is further assumed to have a highest weight submodule, the "left module," and that the quotient by this submodule yields another highest weight module, the "right module." Such modules, which have been called staggered, have appeared repeatedly in the logarithmic conformal field theory literature, but their theory has not been explored in full generality. Here, such a theory is developed for the Virasoro algebra using rather elementary techniques. The focus centers on two different but related questions typically encountered in practical studies: How can one identify a given staggered module, and how can one demonstrate the existence of a proposed staggered module. Given just the values of the highest weights of the left and right modules, themselves subject to simple necessary conditions, invariants are defined which together with the knowledge of the left and right modules uniquely identify a staggered module. The possible values of these invariants form a vector space of dimension 0, 1, or 2, and the structures of the left and right modules limit the isomorphism classes of the corresponding staggered modules to an affine subspace (possibly empty). The number of invariants and affine restrictions is purely determined by the structures of the left and right modules. Moreover, in order to facilitate applications, the expressions for the invariants and restrictions are given by formulas as explicit as possible (they generally rely on expressions for Virasoro singular vectors). Finally, the text is liberally peppered throughout with examples illustrating the general concepts. These have been carefully chosen for their physical relevance or for the novel features they exhibit.

  3. Weyl modules, demazure modules, KR-modules, crystals, fusion products and limit constructions

    OpenAIRE

    Fourier, G.; Littelmann, P.

    2007-01-01

    We study finite dimensional representations of current algebras, loop algebras and their quantized versions. For the current algebra of a simple Lie algebra of type {\\tt ADE}, we show that Kirillov-Reshetikhin modules and Weyl modules are in fact all Demazure modules. As a consequence one obtains an elementary proof of the dimension formula for Weyl modules for the current and the loop algebra. Further, we show that the crystals of the Weyl and the Demazure module are the same up to some addi...

  4. Brownian modulated optical nanoprobes

    International Nuclear Information System (INIS)

    Behrend, C.J.; Anker, J.N.; Kopelman, R.

    2004-01-01

    Brownian modulated optical nanoprobes (Brownian MOONs) are fluorescent micro- and nanoparticles that resemble moons: one hemisphere emits a bright fluorescent signal, while an opaque metal darkens the other hemisphere. Brownian motion causes the particles to tumble and blink erratically as they rotate literally through the phases of the moon. The fluctuating probe signals are separated from optical and electronic backgrounds using principal components analysis or images analysis. Brownian MOONs enable microrheological measurements on size scales and timescales that are difficult to study with other methods. Local chemical concentrations can be measured simultaneously, using spectral characteristics of indicator dyes embedded within the MOONs

  5. Oscillator, neutron modulator

    International Nuclear Information System (INIS)

    Agaisse, R.; Leguen, R.; Ombredane, D.

    1960-01-01

    The authors present a mechanical device and an electronic control circuit which have been designed to sinusoidally modulate the reactivity of the Proserpine atomic pile. The mechanical device comprises an oscillator and a mechanism assembly. The oscillator is made of cadmium blades which generate the reactivity oscillation. The mechanism assembly comprises a pulse generator for cycle splitting, a gearbox and an engine. The electronic device comprises or performs pulse detection, an on-off device, cycle pulse shaping, phase separation, a dephasing amplifier, electronic switches, counting scales, and control devices. All these elements are briefly presented

  6. CDC 7600 Module

    CERN Multimedia

    1970-01-01

    The CDC 7600 has been created by Seymour Cray. It was designed to be compatible with the 6600, which allows for a substantial increase in performance. Furthermore the rise of new technologies has enabled this performance by reducing the minor cycle clock period from 100 ns to 27.5 ns (4 time faster). A very large machine, the 7600 had over 120 miles of hand-wired interconnections. It was the most powerful computer of its time. However, this speed caused a ground-loop problem causing intermittent faults, and eventually requiring all modules to be fitted with sheathed rubber bands. The CDC 7600 was replaced in 1983 by CRAY-1A.

  7. The Role of Protein Elongation Factor EEF1A2 in Breast Cancer

    National Research Council Canada - National Science Library

    Lee, Jonathan M

    2004-01-01

    ... overexpression can be used as a breast cancer prognostic factor. In addition, we proposed to test the idea that EEF1A2 expression modulates sensitivity to cisplatin and taxol and that EEF1A2-inactivation could be used as a treatment for breast cancer...

  8. Processing module operating methods, processing modules, and communications systems

    Science.gov (United States)

    McCown, Steven Harvey; Derr, Kurt W.; Moore, Troy

    2014-09-09

    A processing module operating method includes using a processing module physically connected to a wireless communications device, requesting that the wireless communications device retrieve encrypted code from a web site and receiving the encrypted code from the wireless communications device. The wireless communications device is unable to decrypt the encrypted code. The method further includes using the processing module, decrypting the encrypted code, executing the decrypted code, and preventing the wireless communications device from accessing the decrypted code. Another processing module operating method includes using a processing module physically connected to a host device, executing an application within the processing module, allowing the application to exchange user interaction data communicated using a user interface of the host device with the host device, and allowing the application to use the host device as a communications device for exchanging information with a remote device distinct from the host device.

  9. Increased thromboxane biosynthesis is associated with poststroke dementia

    NARCIS (Netherlands)

    F. van Kooten (Fop); G. Ciabattoni; P.J. Koudstaal (Peter Jan); D.E. Grobbee (Diederick); C. Kluft (Cornelius); C. Patrono

    1999-01-01

    textabstractBACKGROUND AND PURPOSE: It has been suggested that daily intake of aspirin is associated with a reduction of cognitive decline, both in normal and in demented subjects, but the mechanism is unclear. We have therefore studied the relationship between

  10. Thromboxane biosynthesis in stroke and post-stroke dementia

    NARCIS (Netherlands)

    F. van Kooten (Fop)

    2002-01-01

    textabstractWith 25 to 30 thousand new patients per year and an incidence of 170/100.000, stroke is a major health problem in the Netherlands, as it is in other western countries. It accounts for almost I 0% of the annual death in the Netherlands. Approximately 80% of stroke is of ischemic

  11. Phase ramping and modulation of reflectometer signals

    International Nuclear Information System (INIS)

    Conway, G.; Bartlett, D.; Stott, P.

    1999-06-01

    The phase and amplitude signals of JET heterodyne reflectometers show varying levels of high frequency turbulence superimposed on a slow changing mean. The phase signal also shows multi-radian (>1 fringe) variations with two quite different time scales (2-10ms and sub-ms). In both cases the mean reflected power, together with turbulent phase and amplitude fluctuation levels, are modulated synchronously with the phase fringes. The slow fringes appear to result from radial movement of the cutoff layer with the amplitude modulation possibly due to multiple reflection between plasma and wall. The fast fringes occur in intermittent bursts and appear to be phase runaway resulting from antenna misalignment. Using a 2D physical optics simulation code it is possible to replicate the fast bursts of phase runaway from steady-state turbulence and misaligned antennas. This offers a possible alternative explanation for some of the observations of bursting turbulence seen in reflectometer signals. (author)

  12. Aperture modulated arc therapy

    International Nuclear Information System (INIS)

    Crooks, S M; Wu, Xiaodong; Takita, C; Watzich, M; Xing Lei

    2003-01-01

    We show that it is possible to translate an intensity modulated radiation therapy (IMRT) treatment plan and deliver it as a single arc. This technique is referred to in this paper as aperture modulation arc therapy (AMAT). During this arc, the MLC leaves do not conform to the projection of the target PTV and the machine output of the accelerator has a constant value. Dose was calculated using the CORVUS 4.0 IMRT system, which uses a pencil beam dose algorithm, and treatments were delivered using a Varian 2100C/D Clinac. Results are presented for a head and neck and a prostate case, showing the equivalence of the IMRT and the translated AMAT delivery. For a prostate AMAT delivery, coronal plane film dose for the IMRT and AMAT deliveries agreed within 7.19 ± 6.62%. For a meningioma the coronal plane dose distributions were similar to a value of 4.6 ± 6.62%. Dose to the isocentre was measured as being within 2% of the planned value in both cases

  13. Whole Module Offgas Test Report: Space-Xl Dragon Module

    Science.gov (United States)

    James, John T.

    2012-01-01

    On September 26 and September 28,2012 a chemist from the JSC Toxicology Group acquired samples of air in 500 m1 evacuated canisters from the sealed Space-Xl Dragon Module. One sample was also acquired from Space-X Facility near the module at the start of the test. Samples of the module air were taken in triplicate once the module had been sealed, and then taken again in triplicate 1.98 days later. Ofthe triplicate samples, the first served as a line purge, and the last two were analyzed. The results of 5 samples are reported.

  14. Adenosine A2A receptors and A2A receptor heteromers as key players in striatal function

    Directory of Open Access Journals (Sweden)

    Sergi eFerre

    2011-06-01

    Full Text Available A very significant density of adenosine adenosine A2A receptors (A2ARs is present in the striatum, where they are preferentially localized postsynaptically in striatopallidal medium spiny neurons (MSNs. In this localization A2ARs establish reciprocal antagonistic interactions with dopamine D2 receptors (D2Rs. In one type of interaction, A2AR and D2R are forming heteromers and, by means of an allosteric interaction, A2AR counteracts D2R-mediated inhibitory modulation of the effects of NMDA receptor stimulation in the striato-pallidal neuron. This interaction is probably mostly responsible for the locomotor depressant and activating effects of A2AR agonist and antagonists, respectively. The second type of interaction involves A2AR and D2R that do not form heteromers and takes place at the level of adenylyl-cyclase (AC. Due to a strong tonic effect of endogenous dopamine on striatal D2R, this interaction keeps A2AR from signaling through AC. However, under conditions of dopamine depletion or with blockade of D2R, A2AR-mediated AC activation is unleashed with an increased gene expression and activity of the striato-pallidal neuron and with a consequent motor depression. This interaction is probably the main mechanism responsible for the locomotor depression induced by D2R antagonists. Finally, striatal A2ARs are also localized presynaptically, in cortico-striatal glutamatergic terminals that contact the striato-nigral MSN. These presynaptic A2ARs heteromerize with A1 receptors (A1Rs and their activation facilitates glutamate release. These three different types of A2ARs can be pharmacologically dissected by their ability to bind ligands with different affinity and can therefore provide selective targets for drug development in different basal ganglia disorders.

  15. Modular crystals as modulated structures

    DEFF Research Database (Denmark)

    Elcoro, L.; Perez-Mato, J.M.; Friese, K.

    2008-01-01

    The use of the superspace formalism is extended to the description and refinement of the homologous series of modular structures with two symmetry-related modules with different orientations. The lillianite homologous series has been taken as a study case. Starting from a commensurate modulated...... composite description with two basic subsystems corresponding to the two different modules, it is shown how a more efficient description can be achieved using so-called zigzag modulation functions. These linear zigzag modulations, newly implemented in the program JANA2006, have very large fixed amplitudes...... and introduce in the starting model the two orientations of the underlying module sublattices. We show that a composite approach with this type of function, which treats the cations and anions as two separate subsystems forming a misfit compound, is the most appropriate and robust method for the refinements....

  16. Apparatuses to support photovoltaic modules

    Science.gov (United States)

    Ciasulli, John; Jones, Jason

    2017-08-22

    Methods and apparatuses to support photovoltaic ("PV") modules are described. A saddle bracket has a mounting surface to support one or more PV modules over a tube, a gusset coupled to the mounting surface, and a mounting feature coupled to the gusset to couple to the tube. A grounding washer has a first portion to couple to a support; and a second portion coupled to the first portion to provide a ground path to a PV module. A PV system has a saddle bracket; a PV module over the saddle bracket; and a grounding washer coupled to the saddle bracket and the PV module. Saddle brackets can be coupled to a torque tube at predetermined locations. PV modules can be coupled to the saddle brackets.

  17. Mixed twistor D-modules

    CERN Document Server

    Mochizuki, Takuro

    2015-01-01

    We introduce mixed twistor D-modules and establish their fundamental functorial properties. We also prove that they can be described as the gluing of admissible variations of mixed twistor structures. In a sense, mixed twistor D-modules can be regarded as a twistor version of M. Saito's mixed Hodge modules. Alternatively, they can be viewed as a mixed version of the pure twistor D-modules studied by C. Sabbah and the author. The theory of mixed twistor D-modules is one of the ultimate goals in the study suggested by Simpson's Meta Theorem, and it would form a foundation for the Hodge theory of holonomic D-modules which are not necessarily regular singular.  .

  18. Maslinic acid modulates secreted phospholipase A2-IIA (sPLA2-IIA ...

    Indian Academy of Sciences (India)

    Wei Hsum Yap

    2018-03-29

    Mar 29, 2018 ... Further analysis revealed that sPLA2-IIA only induced modest LDL oxidation and that inhibitory .... COX-2, was also reduced in primary human chondrocyte, primary rat .... oxidation (4.34 nmol MDA/mg protein) compared to native ..... rheumatoid fibroblast-like synoviocyte arachidonic acid meta- bolism.

  19. Photovoltaic concentrator module improvements study

    Energy Technology Data Exchange (ETDEWEB)

    Levy, S.L.; Kerschen, K.A. (Black and Veatch, Kansas City, MO (United States)); Hutchison, G. (Solar Kinetics, Inc., Dallas, TX (United States)); Nowlan, M.J. (Spire Corp., Bedford, MA (United States))

    1991-08-01

    This report presents results of a project to design and fabricate an improved photovoltaic concentrator module. Using previous work as a baseline, this study conducted analyses and testing to select major module components and design features. The lens parquet and concentrator solar cell were selected from the highest performing, available components. A single 185X point-focus module was fabricated by the project team and tested at Sandia. Major module characteristics include a 6 by 4 compression-molded acrylic lens parquet (0.737 m{sup 2} area), twenty-four 0.2 ohms-cm, FZ, p-Si solar cells (1.56 cm{sup 2} area) soldered to ceramic substrates and copper heat spreaders, and an aluminized steel housing with corrugated bottom. This project marked the first attempt to use prismatic covers on solar cells in a high-concentration, point-focus application. Cells with 15 percent metallization were obtained, but problems with the fabrication and placement of prismatic covers on these cells lead to the decision not to use covers in the prototype module. Cell assembly fabrication, module fabrication, and module optical design activities are presented here. Test results are also presented for bare cells, cell assemblies, and module. At operating conditions of 981 watts/m{sup 2} DNI and an estimated cell temperature of 65{degrees}C, the module demonstrated an efficiency of 13.9 percent prior to stressed environmental exposure. 12 refs., 56 figs., 7 tabs.

  20. Adjustable extender for instrument module

    International Nuclear Information System (INIS)

    Sevec, J.B.; Stein, A.D.

    1975-01-01

    A blank extender module used to mount an instrument module in front of its console for repair or test purposes has been equipped with a rotatable mount and means for locking the mount at various angles of rotation for easy accessibility. The rotatable mount includes a horizontal conduit supported by bearings within the blank module. The conduit is spring-biased in a retracted position within the blank module and in this position a small gear mounted on the conduit periphery is locked by a fixed pawl. The conduit and instrument mount can be pulled into an extended position with the gear clearing the pawl to permit rotation and adjustment of the instrument

  1. Perancangan Modul Penggajian Berbasis Odoo

    OpenAIRE

    Koeswanto, Vincent K. Edison; Yulia, Yulia; Adipranata, Rudy

    2016-01-01

    Human Resource Module is one of the modules owned by Odoo. One of the feature of this module is payroll. However, the features is not in accordance with the needs of companies in Indonesia in general. This causes the payroll system in Odoo not suitable to be implemented directly in the company.To solve these problems, author develop the payroll system in Human Resource module in Odoo. The development of this system is preceded by designing and analyze the payroll system at PT X. It also condu...

  2. Adenosine A2B receptor: from cell biology to human diseases

    Science.gov (United States)

    Sun, Ying; Huang, Pingbo

    2016-08-01

    Extracellular adenosine is a ubiquitous signaling molecule that modulates a wide array of biological processes. Recently, significant advances have been made in our understanding of A2B adenosine receptor (A2BAR). In this review, we first summarize some of the general characteristics of A2BAR, and then we describe the multiple binding partners of the receptor, such as newly identified α-actinin-1 and p105, and discuss how these associated proteins could modulate A2BAR’s functions, including certain seemingly paradoxical functions of the receptor. Growing evidence indicates a critical role of A2BAR in cancer, renal disease, and diabetes, in addition to its importance in the regulation of vascular diseases and lung disease. Here, we also discuss the role of A2BAR in cancer, renal disease, and diabetes and the potential of the receptor as a target for treating these three diseases.

  3. Photovoltaic module mounting system

    Science.gov (United States)

    Miros, Robert H. J. [Fairfax, CA; Mittan, Margaret Birmingham [Oakland, CA; Seery, Martin N [San Rafael, CA; Holland, Rodney H [Novato, CA

    2012-04-17

    A solar array mounting system having unique installation, load distribution, and grounding features, and which is adaptable for mounting solar panels having no external frame. The solar array mounting system includes flexible, pedestal-style feet and structural links connected in a grid formation on the mounting surface. The photovoltaic modules are secured in place via the use of attachment clamps that grip the edge of the typically glass substrate. The panel mounting clamps are then held in place by tilt brackets and/or mid-link brackets that provide fixation for the clamps and align the solar panels at a tilt to the horizontal mounting surface. The tilt brackets are held in place atop the flexible feet and connected link members thus creating a complete mounting structure.

  4. Multichip module technology development

    International Nuclear Information System (INIS)

    Kapustinsky, J.S.; Boissevain, J.G.; Muck, R.C.; Smith, G.D.; Wong-Swanson, B.G.; Ziock, H.J.

    1997-01-01

    This is the final report of a one-year, Laboratory Directed Research and Development (LDRD) project at Los Alamos National Laboratory (LANL). A Multichip Module (MCM) was designed and submitted for fabrication to the Lockheed Martin foundry using a licensed process called High Density Interconnect (HDI). The HDI process uses thin film techniques to create circuit interconnect patterns on multiple layers of dielectric film which are deposited directly on top of unpackaged electronic die. This results in an optimally small package that approaches the area of the bare die themselves. This project tested the capability of the Lockheed Martin foundry to produce, in an HDI process, a complex mixed-mode (analog and digital) circuit on a single MCM substrate

  5. Digital Communication and Modulation

    DEFF Research Database (Denmark)

    Sørensen, John Aasted

    2011-01-01

    system. Having passed the course, the student will be able to accomplish the following, within the areas shown below: Model for Communication System. Prepare and explain the functional block in a digital communication system, corresponding to the specific course contents. Model for Communication Channel...... system.   Sessions in class with active participation by the students. The time will be divided between lectures and the students solving problems, including simulating digital communication building blocks in Matlab. Combines lectures and hands-on work. Semester: E2011 Extent: 7.5 ects......, the fundamental principles for modulation and detection in Gaussian noise is treated. This includes the principles for the determination of the bit-error rate for a digital communication system. During the course, a selection of small Matlab exercises are prepared, for simulation of parts of a communication...

  6. Digital Communication and Modulation

    DEFF Research Database (Denmark)

    Sørensen, John Aasted

    2011-01-01

    system. Having passed the course, the student will be able to accomplish the following, within the areas shown below: Model for Communication System. Prepare and explain the functional block in a digital communication system, corresponding to the specific course contents. Model for Communication Channel...... system. Sessions in class with active participation by the students. The time will be divided between lectures and the students solving problems, including simulating digital communication building blocks in Matlab. Combines lectures and hands-on work. Semester: F2011 Extent: 7.5 ects......, the fundamental principles for modulation and detection in Gaussian noise is treated. This includes the principles for the determination of the bit-error rate for a digital communication system. During the course, a selection of small Matlab exercises are prepared, for simulation of parts of a communication...

  7. Modulated convection at high frequencies and large modulation amplitudes

    International Nuclear Information System (INIS)

    Swift, J.B.; Hohenberg, P.C.

    1987-01-01

    Modulated Rayleigh-Benard convection is analyzed for high frequencies and large modulation amplitudes. The linear theory of Gershuni and Zhukhovitskii is generalized to the nonlinear domain, and a subcritical bifurcation to convection is found in agreement with the experiments of Niemela and Donnelly. The crossover between the high-frequency (''Stokes layer'') regime and the low-frequency regime studied previously is analyzed

  8. Modulation masking produced by second-order modulators

    DEFF Research Database (Denmark)

    Füllgrabe, Christian; Moore, Brian C.J.; Demany, Laurent

    2005-01-01

    Recent studies suggest that an auditory nonlinearity converts second-order sinusoidal amplitude modulation (SAM) (i.e., modulation of SAM depth) into a first-order SAM component, which contributes to the perception of second-order SAM. However, conversion may also occur in other ways such as coch...

  9. HEAO A-2 extragalactic results

    Science.gov (United States)

    Boldt, E. A.

    1979-01-01

    The all-sky surveys made with the A-2 instrument aboard HEAO-1 involved spectroscopy over a broad enough band width, with sufficient resolution, to obtain the basic spectral characteristics for two extreme aspects of the extragalactic X-ray sky. The overall spectrum (above 3 KeV) is remarkably well decribed by a thermal model. At the other extreme, the detailed broad-band observations of individual sources are restricted to objects within the present epoch. The objects include several individual active galaxies studied in detail for the first time as well as clusters of galaxies. Relating these results to the vast spatially unresolved hard X-ray flux measured with this instruments as well as the softer X-rays (at less than 3 keV) spatially resolved to high redshifts with the Einstein Observatory remains a challenge.

  10. Mutually-modulated cross-gain modulation and slow light

    International Nuclear Information System (INIS)

    Sternklar, Shmuel; Sarid, Eyal; Wart, Maxim; Granot, Er'el

    2010-01-01

    The interaction of pump and Stokes light in a Brillouin medium, where both beams are modulated, can be utilized for controlling the group velocity of the amplified Stokes (or depleted pump). The dependence of the group velocity for this mutually-modulated cross-gain modulation (MMXGM) technique on the Brillouin gain parameter is studied. A sharp transition to slow light occurs in the G 1 α/β≈1 regime, where G 1 is the Brillouin gain parameter, and α and β are the pump and Stokes modulation indices, respectively. A comparison of MMXGM slow light to the Brillouin dispersion-based slow-light technique reveals the fundamental differences between them. The formation of higher harmonics of the modulation frequency is also discussed. The theoretical predictions are experimentally corroborated and potential applications in fiber-based sensing and interferometry are discussed

  11. Force Modulator System

    Energy Technology Data Exchange (ETDEWEB)

    Redmond Clark

    2009-04-30

    Many metal parts manufacturers use large metal presses to shape sheet metal into finished products like car body parts, jet wing and fuselage surfaces, etc. These metal presses take sheet metal and - with enormous force - reshape the metal into a fully formed part in a manner of seconds. Although highly efficient, the forces involved in forming metal parts also damage the press itself, limit the metals used in part production, slow press operations and, when not properly controlled, cause the manufacture of large volumes of defective metal parts. To date, the metal-forming industry has not been able to develop a metal-holding technology that allows full control of press forces during the part forming process. This is of particular importance in the automotive lightweighting efforts under way in the US automotive manufacturing marketplace. Metalforming Controls Technology Inc. (MC2) has developed a patented press control system called the Force Modulator that has the ability to control these press forces, allowing a breakthrough in stamping process control. The technology includes a series of hydraulic cylinders that provide controlled tonnage at all points in the forming process. At the same time, the unique cylinder design allows for the generation of very high levels of clamping forces (very high tonnages) in very small spaces; a requirement for forming medium and large panels out of HSS and AHSS. Successful production application of these systems testing at multiple stamping operations - including Ford and Chrysler - has validated the capabilities and economic benefits of the system. Although this technology has been adopted in a number of stamping operations, one of the primary barriers to faster adoption and application of this technology in HSS projects is system cost. The cost issue has surfaced because the systems currently in use are built for each individual die as a custom application, thus driving higher tooling costs. This project proposed to better

  12. Acceleration recorder and playback module

    Science.gov (United States)

    Bozeman, Richard J., Jr.

    1994-11-01

    The present invention is directed to methods and apparatus relating to an accelerometer electrical signal recorder and playback module. The recorder module may be manufactured in lightweight configuration and includes analog memory components to store data. Signal conditioning circuitry is incorporated into the module so that signals may be connected directly from the accelerometer to the recorder module. A battery pack may be included for powering both the module and the accelerometer. Timing circuitry is included to control the time duration within which data is recorded or played back so as to avoid overloading the analog memory components. Multiple accelerometer signal recordings may be taken simultaneously without analog to digital circuits, multiplexing circuitry or software to compensate for the effects of multiplexing the signals.

  13. Biological modulation of tectonics

    Science.gov (United States)

    Sleep, N. H.; Bird, D. K.

    2008-12-01

    Photosynthesis has had geologic consequences over the Earth's history. In addition to modifying Earth's atmosphere and ocean chemistry, it has also modulated tectonic processes through enhanced weathering and modification of the nature and composition of sedimentary rocks within fold mountain belts and convergent margins. Molecular biological studies indicate that bacterial photosynthesis evolved just once and that most bacterial clades descend from this photosynthetic common ancestor. Iron-based photosynthesis (ideally 4FeO + CO2 + H2O = 2Fe2O3 + CH2O) was the most bountiful anoxygenic niche on land. The back reaction provided energy to heterotrophic microbes and returned FeO to the photosynthetic microbes. Bacterial land colonists evolved into ecosystems that effectively weathered FeO-bearing minerals and volcanic glass. Clays, sands, and dissolved cations from the weathering process entered the ocean and formed our familiar classes sedimentary rocks: shales, sandstones, and carbonates. Marine photosynthesis caused organic carbon to accumulate in black shales. In contrast, non-photosynthetic ecosystems do not cause organic carbon to accumulate in shale. These evolutionary events occurred before 3.8 Ga as black shales are among the oldest rock types (Rosing and Frei, Earth Planet. Sci. Lett. 217, 237-244, 2004). Thick sedimentary sequences deformed into fold mountain belts. They remelted at depth to form granitic rocks (Rosing et al., Palaeoclimatol. Palaeoecol. 232, 99-11, 2006). Regions of outcropping low-FeO rocks including granites, quartzites, and some shales were a direct result. This dearth of FeO favored the evolution of oxic photosynthesis of cyanobacteria from photosynthetic soil bacteria. Black shales have an additional modulation effect on tectonics as they concentrate radioactive elements, particularly uranium (e.g. so that the surface heat flow varies by a factor of ca. 2). Thick sequences of black shales at continental rises of passive margins are

  14. Modulator-free quadrature amplitude modulation signal synthesis

    Science.gov (United States)

    Liu, Zhixin; Kakande, Joseph; Kelly, Brian; O'Carroll, John; Phelan, Richard; Richardson, David J.; Slavík, Radan

    2014-12-01

    The ability to generate high-speed on-off-keyed telecommunication signals by directly modulating a semiconductor laser’s drive current was one of the most exciting prospective applications of the nascent field of laser technology throughout the 1960s. Three decades of progress led to the commercialization of 2.5 Gbit s-1-per-channel submarine fibre optic systems that drove the growth of the internet as a global phenomenon. However, the detrimental frequency chirp associated with direct modulation forced industry to use external electro-optic modulators to deliver the next generation of on-off-keyed 10 Gbit s-1 systems and is absolutely prohibitive for today’s (>)100 Gbit s-1 coherent systems, which use complex modulation formats (for example, quadrature amplitude modulation). Here we use optical injection locking of directly modulated semiconductor lasers to generate complex modulation format signals showing distinct advantages over current and other currently researched solutions.

  15. 47 CFR 78.115 - Modulation limits.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 4 2010-10-01 2010-10-01 false Modulation limits. 78.115 Section 78.115... SERVICE Technical Regulations § 78.115 Modulation limits. (a) If amplitude modulation is employed, negative modulation peaks shall not exceed 100 percent modulation. [37 FR 3292, Feb. 12, 1972, as amended...

  16. Study of a pulsed capillary discharge with a modulated radius

    NARCIS (Netherlands)

    Broks, B.H.P.; Dijk, van W.; Mullen, van der J.J.A.M.; Veldhuizen, van E.M.

    2005-01-01

    In this contribution, we present a plasma physical model of a pulsed capillary discharge with a modulated radius. Using a 2D time-dependent model, we have modeled the plasma and wall properties of this channel. It was found that properties of the central plasma are different than the properties of a

  17. Modulated Source Interferometry with Combined Amplitude and Frequency Modulation

    Science.gov (United States)

    Gutierrez, Roman C. (Inventor)

    1998-01-01

    An improved interferometer is produced by modifying a conventional interferometer to include amplitude and/or frequency modulation of a coherent light source at radio or higher frequencies. The phase of the modulation signal can be detected in an interfering beam from an interferometer and can be used to determine the actual optical phase of the beam. As such, this improvement can be adapted to virtually any two-beam interferometer, including: Michelson, Mach-Zehnder, and Sagnac interferometers. The use of an amplitude modulated coherent tight source results in an interferometer that combines the wide range advantages of coherent interferometry with the precise distance measurement advantages of white light interferometry.

  18. OCGen Module Mooring Project

    Energy Technology Data Exchange (ETDEWEB)

    McEntee, Jarlath [Ocean Renewable Power Company, LLC, Portland, ME (United States)

    2015-02-06

    Ocean Renewable Power Company's OCGen Module Mooring Project provided an extensive research, design, development, testing and data collection effort and analysis conducted with respect to a positively buoyant, submerged MHK device secured to the seabed using a tensioned mooring system. Different analytic tools were evaluated for their utility in the design of submerged systems and their moorings. Deployment and testing of a prototype OCGen® system provided significant data related to mooring line loads and system attitude and station keeping. Mooring line loads were measured in situ and reported against flow speeds. The Project made a significant step in the development of designs, methodologies and practices related to floating and mooring of marine hydrokinetic (MHK) devices. Importantly for Ocean Renewable Power Company, the Project provided a sound basis for advancing a technically and commercially viable OCGen® Power System. The OCGen® Power System is unique in the MHK industry and, in itself, offers distinct advantages of MHK devices that are secured to the seabed using fixed structural frames. Foremost among these advantages are capital and operating cost reductions and increased power extraction by allowing the device to be placed at the most energetic level of the water column.

  19. Diamond pixel modules

    International Nuclear Information System (INIS)

    Asner, D.; Barbero, M.; Bellini, V.; Belyaev, V.; Brom, J-M.; Bruzzi, M.; Chren, D.; Cindro, V.; Claus, G.; Cristinziani, M.; Costa, S.; D'Alessandro, R.; Boer, W. de; Dobos, D.; Dolenc, I.; Dulinski, W.; Duris, J.; Eremin, V.; Eusebi, R.; Frais-Koelbl, H.

    2011-01-01

    With the commissioning of the LHC in 2010 and upgrades expected in 2015, ATLAS and CMS are planning to upgrade their innermost tracking layers with radiation hard technologies. Chemical Vapor Deposition diamond has been used extensively in beam conditions monitors as the innermost detectors in the highest radiation areas of BaBar, Belle, CDF and all LHC experiments. This material is now being considered as a sensor material for use very close to the interaction region where the most extreme radiation conditions exist. Recently the RD42 collaboration constructed, irradiated and tested polycrystalline and single-crystal chemical vapor deposition diamond sensors to the highest fluences expected at the super-LHC. We present beam test results of chemical vapor deposition diamond up to fluences of 1.8x10 16 protons/cm 2 illustrating that both polycrystalline and single-crystal chemical vapor deposition diamonds follow a single damage curve. We also present beam test results of irradiated complete diamond pixel modules.

  20. Diamond pixel modules

    Energy Technology Data Exchange (ETDEWEB)

    Asner, D. [Carleton University, Ottawa (Canada); Barbero, M. [Universitaet Bonn (Germany); Bellini, V. [INFN/University of Catania (Italy); Belyaev, V. [MEPHI Institute, Moscow (Russian Federation); Brom, J-M. [IPHC, Strasbourg (France); Bruzzi, M. [INFN/University of Florence (Italy); Chren, D. [Czech Technical University, Prague (Czech Republic); Cindro, V. [Jozef Stefan Institute, Ljubljana (Slovenia); Claus, G. [IPHC, Strasbourg (France); Cristinziani, M. [Universitaet Bonn (Germany); Costa, S. [INFN/University of Catania (Italy); D' Alessandro, R. [Department of Energetics/INFN Florence (Italy); Boer, W. de [Universitaet Karlsruhe, Karlsruhe (Germany); Dobos, D. [CERN, Geneva (Switzerland); Dolenc, I. [Jozef Stefan Institute, Ljubljana (Slovenia); Dulinski, W. [IPHC, Strasbourg (France); Duris, J. [UCLA, Los Angeles, CA (United States); Eremin, V. [Ioffe Institute, St. Petersburg (Russian Federation); Eusebi, R. [FNAL, Batavia (United States); Frais-Koelbl, H. [Fachhochschule fuer Wirtschaft und Technik, Wiener Neustadt (Austria)

    2011-04-21

    With the commissioning of the LHC in 2010 and upgrades expected in 2015, ATLAS and CMS are planning to upgrade their innermost tracking layers with radiation hard technologies. Chemical Vapor Deposition diamond has been used extensively in beam conditions monitors as the innermost detectors in the highest radiation areas of BaBar, Belle, CDF and all LHC experiments. This material is now being considered as a sensor material for use very close to the interaction region where the most extreme radiation conditions exist. Recently the RD42 collaboration constructed, irradiated and tested polycrystalline and single-crystal chemical vapor deposition diamond sensors to the highest fluences expected at the super-LHC. We present beam test results of chemical vapor deposition diamond up to fluences of 1.8x10{sup 16} protons/cm{sup 2} illustrating that both polycrystalline and single-crystal chemical vapor deposition diamonds follow a single damage curve. We also present beam test results of irradiated complete diamond pixel modules.

  1. Intensity modulated conformal radiotherapy

    International Nuclear Information System (INIS)

    Noel, Georges; Moty-Monnereau, Celine; Meyer, Aurelia; David, Pauline; Pages, Frederique; Muller, Felix; Lee-Robin, Sun Hae; David, Denis Jean

    2006-12-01

    This publication reports the assessment of intensity-modulated conformal radiotherapy (IMCR). This assessment is based on a literature survey which focussed on indications, efficiency and safety on the short term, on the risk of radio-induced cancer on the long term, on the role in the therapeutic strategy, on the conditions of execution, on the impact on morbidity-mortality and life quality, on the impact on the health system and on public health policies and program. This assessment is also based on the opinion of a group of experts regarding the technical benefit of IMCR, its indications depending on the cancer type, safety in terms of radio-induced cancers, and conditions of execution. Before this assessment, the report thus indicates indications for which the use of IMCR can be considered as sufficient or not determined. It also proposes a technical description of IMCR and helical tomo-therapy, discusses the use of this technique for various pathologies or tumours, analyses the present situation of care in France, and comments the identification of this technique in foreign classifications

  2. Living Systems Energy Module

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-09-26

    The Living Systems Energy Module, renamed Voyage from the Sun, is a twenty-lesson curriculum designed to introduce students to the major ways in which energy is important in living systems. Voyage from the Sun tells the story of energy, describing its solar origins, how it is incorporated into living terrestrial systems through photosynthesis, how it flows from plants to herbivorous animals, and from herbivores to carnivores. A significant part of the unit is devoted to examining how humans use energy, and how human impact on natural habitats affects ecosystems. As students proceed through the unit, they read chapters of Voyage from the Sun, a comic book that describes the flow of energy in story form (Appendix A). During the course of the unit, an ``Energy Pyramid`` is erected in the classroom. This three-dimensional structure serves as a classroom exhibit, reminding students daily of the importance of energy and of the fragile nature of our living planet. Interactive activities teach students about adaptations that allow plants and animals to acquire, to use and to conserve energy. A complete list of curricular materials and copies of all activity sheets appear in Appendix B.

  3. Modelling modulation perception : modulation low-pass filter or modulation filter bank?

    NARCIS (Netherlands)

    Dau, T.; Kollmeier, B.; Kohlrausch, A.G.

    1995-01-01

    In current models of modulation perception, the stimuli are first filtered and nonlinearly transformed (mostly half-wave rectified). In order to model the low-pass characteristic of measured modulation transfer functions, the next stage in the models is a first-order low-pass filter with a typical

  4. Superstability for Generalized Module Left Derivations and Generalized Module Derivations on a Banach Module (I

    Directory of Open Access Journals (Sweden)

    Huai-Xin Cao

    2009-01-01

    Full Text Available We discuss the superstability of generalized module left derivations and generalized module derivations on a Banach module. Let 𝒜 be a Banach algebra and X a Banach 𝒜-module, f:X→X and g:𝒜→𝒜. The mappings Δf,g1, Δf,g2, Δf,g3, and Δf,g4 are defined and it is proved that if ∥Δf,g1(x,y,z,w∥ (resp., ∥Δf,g3(x,y,z,w,α,β∥ is dominated by φ(x,y,z,w, then f is a generalized (resp., linear module-𝒜 left derivation and g is a (resp., linear module-X left derivation. It is also shown that if ∥Δf,g2(x,y,z,w∥ (resp., ∥Δf,g4(x,y,z,w,α,β∥ is dominated by φ(x,y,z,w, then f is a generalized (resp., linear module-𝒜 derivation and g is a (resp., linear module-X derivation.

  5. Ring resonator-based on-chip modulation transformer for high-performance phase-modulated microwave photonic links.

    Science.gov (United States)

    Zhuang, Leimeng; Taddei, Caterina; Hoekman, Marcel; Leinse, Arne; Heideman, René; van Dijk, Paulus; Roeloffzen, Chris

    2013-11-04

    In this paper, we propose and experimentally demonstrate a novel wideband on-chip photonic modulation transformer for phase-modulated microwave photonic links. The proposed device is able to transform phase-modulated optical signals into intensity-modulated versions (or vice versa) with nearly zero conversion of laser phase noise to intensity noise. It is constructed using waveguide-based ring resonators, which features simple architecture, stable operation, and easy reconfigurability. Beyond the stand-alone functionality, the proposed device can also be integrated with other functional building blocks of photonic integrated circuits (PICs) to create on-chip complex microwave photonic signal processors. As an application example, a PIC consisting of two such modulation transformers and a notch filter has been designed and realized in TriPleX(TM) waveguide technology. The realized device uses a 2 × 2 splitting circuit and 3 ring resonators with a free spectral range of 25 GHz, which are all equipped with continuous tuning elements. The device can perform phase-to-intensity modulation transform and carrier suppression simultaneously, which enables high-performance phase-modulated microwave photonics links (PM-MPLs). Associated with the bias-free and low-complexity advantages of the phase modulators, a single-fiber-span PM-MPL with a RF bandwidth of 12 GHz (3 dB-suppression band 6 to 18 GHz) has been demonstrated comprising the proposed PIC, where the achieved spurious-free dynamic range performance is comparable to that of Class-AB MPLs using low-biased Mach-Zehnder modulators.

  6. hybrid modulation scheme fo rid modulation scheme fo dulation

    African Journals Online (AJOL)

    eobe

    control technique is done through simulations and ex control technique .... HYBRID MODULATION SCHEME FOR CASCADED H-BRIDGE INVERTER CELLS. C. I. Odeh ..... and OR operations. Referring to ... MATLAB/SIMULINK environment.

  7. Reachability modules for the description logic SRIQ

    CSIR Research Space (South Africa)

    Nortje, R

    2013-12-01

    Full Text Available In this paper we investigate module extraction for the Description Logic SRIQ. We formulate modules in terms of the reachability problem for directed hypergraphs. Using inseperability relations, we investigate the module-theoretic properties...

  8. Novel approaches for targeting the adenosine A2A receptor.

    Science.gov (United States)

    Yuan, Gengyang; Gedeon, Nicholas G; Jankins, Tanner C; Jones, Graham B

    2015-01-01

    The adenosine A2A receptor (A2AR) represents a drug target for a wide spectrum of diseases. Approaches for targeting this membrane-bound protein have been greatly advanced by new stabilization techniques. The resulting X-ray crystal structures and subsequent analyses provide deep insight to the A2AR from both static and dynamic perspectives. Application of this, along with other biophysical methods combined with fragment-based drug design (FBDD), has become a standard approach in targeting A2AR. Complementarities of in silico screening based- and biophysical screening assisted- FBDD are likely to feature in future approaches in identifying novel ligands against this key receptor. This review describes evolution of the above approaches for targeting A2AR and highlights key modulators identified. It includes a review of: adenosine receptor structures, homology modeling, X-ray structural analysis, rational drug design, biophysical methods, FBDD and in silico screening. As a drug target, the A2AR is attractive as its function plays a role in a wide spectrum of diseases including oncologic, inflammatory, Parkinson's and cardiovascular diseases. Although traditional approaches such as high-throughput screening and homology model-based virtual screening (VS) have played a role in targeting A2AR, numerous shortcomings have generally restricted their applications to specific ligand families. Using stabilization methods for crystallization, X-ray structures of A2AR have greatly accelerated drug discovery and influenced development of biophysical-in silico hybrid screening methods. Application of these new methods to other ARs and G-protein-coupled receptors is anticipated in the future.

  9. Coolant channel module CCM

    International Nuclear Information System (INIS)

    Hoeld, Alois

    2007-01-01

    A complete and detailed description of the theoretical background of an '(1D) thermal-hydraulic drift-flux based mixture-fluid' coolant channel model and its resulting module CCM will be presented. The objective of this module is to simulate as universally as possible the steady state and transient behaviour of the key characteristic parameters of a single- or two-phase fluid flowing within any type of heated or non-heated coolant channel. Due to the possibility that different flow regimes can appear along any channel, such a 'basic (BC)' 1D channel is assumed to be subdivided into a number of corresponding sub-channels (SC-s). Each SC can belong to only two types of flow regime, an SC with just a single-phase fluid, containing exclusively either sub-cooled water or superheated steam, or an SC with a two-phase mixture flow. After an appropriate nodalisation of such a BC (and therefore also its SC-s) a 'modified finite volume method' has been applied for the spatial discretisation of the partial differential equations (PDE-s) which represent the basic conservation equations of thermal-hydraulics. Special attention had to be given to the possibility of variable SC entrance or outlet positions (which describe boiling boundaries or mixture levels) and thus the fact that an SC can even disappear or be created anew. The procedure yields for each SC type (and thus the entire BC), a set of non-linear ordinary 1st order differential equations (ODE-s). To link the resulting mean nodal with the nodal boundary function values, both of which are present in the discretised differential equations, a special quadratic polygon approximation procedure (PAX) had to be constructed. Together with the very thoroughly tested packages for drift-flux, heat transfer and single- and two-phase friction factors this procedure represents the central part of the here presented 'Separate-Region' approach, a theoretical model which provides the basis to the very effective working code package CCM

  10. Photovoltaic module with adhesion promoter

    Science.gov (United States)

    Xavier, Grace

    2013-10-08

    Photovoltaic modules with adhesion promoters and methods for fabricating photovoltaic modules with adhesion promoters are described. A photovoltaic module includes a solar cell including a first surface and a second surface, the second surface including a plurality of interspaced back-side contacts. A first glass layer is coupled to the first surface by a first encapsulating layer. A second glass layer is coupled to the second surface by a second encapsulating layer. At least a portion of the second encapsulating layer is bonded directly to the plurality of interspaced back-side contacts by an adhesion promoter.

  11. High Order Modulation Protograph Codes

    Science.gov (United States)

    Nguyen, Thuy V. (Inventor); Nosratinia, Aria (Inventor); Divsalar, Dariush (Inventor)

    2014-01-01

    Digital communication coding methods for designing protograph-based bit-interleaved code modulation that is general and applies to any modulation. The general coding framework can support not only multiple rates but also adaptive modulation. The method is a two stage lifting approach. In the first stage, an original protograph is lifted to a slightly larger intermediate protograph. The intermediate protograph is then lifted via a circulant matrix to the expected codeword length to form a protograph-based low-density parity-check code.

  12. Light intensity modulation in phototherapy

    Science.gov (United States)

    Lukyanovich, P. A.; Zon, B. A.; Kunin, A. A.; Pankova, S. N.

    2015-04-01

    A hypothesis that blocking ATP synthesis is one of the main causes of the stimulating effect is considered based on analysis of the primary photostimulation mechanisms. The light radiation intensity modulation is substantiated and the estimates of such modulation parameters are made. An explanation is offered to the stimulation efficiency decrease phenomenon at the increase of the radiation dose during the therapy. The results of clinical research of the medical treatment in preventive dentistry are presented depending on the spectrum and parameters of the light flux modulation.

  13. Complex Wavelet Based Modulation Analysis

    DEFF Research Database (Denmark)

    Luneau, Jean-Marc; Lebrun, Jérôme; Jensen, Søren Holdt

    2008-01-01

    Low-frequency modulation of sound carry important information for speech and music. The modulation spectrum i commonly obtained by spectral analysis of the sole temporal envelopes of the sub-bands out of a time-frequency analysis. Processing in this domain usually creates undesirable distortions...... polynomial trends. Moreover an analytic Hilbert-like transform is possible with complex wavelets implemented as an orthogonal filter bank. By working in an alternative transform domain coined as “Modulation Subbands”, this transform shows very promising denoising capabilities and suggests new approaches for joint...

  14. Induced modules over group algebras

    CERN Document Server

    Karpilovsky, Gregory

    1990-01-01

    In 1898 Frobenius discovered a construction which, in present terminology, associates with every module of a subgroup the induced module of a group. This construction proved to be of fundamental importance and is one of the basic tools in the entire theory of group representations.This monograph is designed for research mathematicians and advanced graduate students and gives a picture of the general theory of induced modules as it exists at present. Much of the material has until now been available only in research articles. The approach is not intended to be encyclopedic, rather each topic is

  15. Improved ATIR concentrator photovoltaic module

    Science.gov (United States)

    Adriani, Paul M.; Mao, Erwang

    2013-09-01

    Novel aggregated total internal reflection (ATIR) concentrator photovoltaic module design comprises 2-D shaped primary and secondary optics that effectively combine optical efficiency, low profile, convenient range of acceptance angles, reliability, and manufacturability. This novel optical design builds upon previous investigations by improving the shapes of primary and secondary optics to enable improved long-term reliability and manufacturability. This low profile, low concentration (5x to 10x) design fits well with one-axis trackers that are often used for flat plate crystalline silicon photovoltaic modules in large scale ground mount installations. Standard mounting points, materials, and procedures apply without changes from flat plate modules.

  16. Ammonia corrodes solar modules; Salmiakgeist greift Module an

    Energy Technology Data Exchange (ETDEWEB)

    Petzold, Katrin

    2011-07-01

    Ammonia is an aggressive gas produced in animal shelters, which may cause corrosion of solar modules. Various institutions, e.g. DLG and TUeV Rheinland, therefore offer an ammonia test for solar modules. The TUeV Rheinland recently commissioned a walk-in test chamber and now issues an official seal of approval, while the DLG doubts the practical value of the test.

  17. Modulation of lymphopoiesis

    Energy Technology Data Exchange (ETDEWEB)

    Rosse, C.

    1991-01-01

    During the current project period we have demonstrated correspondence between animal models and in vitro models of modulated lymphopoiesis. Our finding that G-CSF, a growth factor for neutrophil granulocytes, suppresses lymphopoiesis in long term bone marrow cultures (LTBMC) has important implications both for understanding the regulatory mechanisms of hemopoiesis and for clinical use of recombinant growth factors that are beginning to be widely used for the treatment of a variety of diseases. During the present project period we adopted LTBMC systems developed by others for the purposes of our specific aims. Also we developed a novel long term culture system for NK cells. The discovery of a new growth factor, O-CSF, specific for osteoclasts and the establishment of a clonal assay system that provides evidence for a new class of hemopoietic progenitor cells, the osteoclast progenitor, are important contributions. Given the important role T cells play in the immune response and in the regulation of other lymphohemopoietic cell lineages through the lymphokines they secrete, the need for an in vitro system that lends itself to the analysis of T cell maturation and to the testing of factors that may adversely affect T lymphopoiesis cannot be overemphasized. We believe that we can exploit an advantageous set of circumstances that present an excellent opportunity for initiating a focused experimental program for developing such a system. By a systematic and selective analysis of molecular interactions between heterogenous thymic stromal cells and T cell progenitors at different stages of maturation, it will be possible for our program to define the complement of critical cellular interactions on which successive stages of T lymphopoiesis depend. The experiments we propose will lay a rational foundation for the development of a long term culture system for T lymphopoiesis. 24 refs., 7 figs.

  18. Cosmic ray modulation

    Science.gov (United States)

    Agarwal Mishra, Rekha; Mishra, Rajesh Kumar

    2016-07-01

    Propagation of cosmic rays to and inside the heliosphere, encounter an outward moving solar wind with cyclic magnetic field fluctuation and turbulence, causing convection and diffusion in the heliosphere. Cosmic ray counts from the ground ground-based neutron monitors at different cut of rigidity show intensity changes, which are anti-correlated with sunspot numbers. They also lose energy as they propagate towards the Earth and experience various types of modulations due to different solar activity indices. In this work, we study the first three harmonics of cosmic ray intensity on geo-magnetically quiet days over the period 1965-2014 for Beijing, Moscow and Tokyo neutron monitoring stations located at different cut off rigidity. The amplitude of first harmonic remains high for low cutoff rigidity as compared to high cutoff rigidity on quiet days. The diurnal amplitude significantly decreases during solar activity minimum years. The diurnal time of maximum significantly shifts to an earlier time as compared to the corotational direction having different cutoff rigidities. The time of maximum for first harmonic significantly shifts towards later hours and for second harmonic it shifts towards earlier hours at low cutoff rigidity station as compared to the high cut off rigidity station on quiet days. The amplitude of second/third harmonics shows a good positive correlation with solar wind velocity, while the others (i.e. amplitude and phase) have no significant correlation on quiet days. The amplitude and direction of the anisotropy on quiet days does not show any significant dependence on high-speed solar wind streams for these neutron monitoring stations of different cutoff rigidity threshold. Keywords: cosmic ray, cut off rigidity, quiet days, harmonics, amplitude, phase.

  19. Multiplication modules over non-commutative rings

    International Nuclear Information System (INIS)

    Tuganbaev, A A

    2003-01-01

    It is proved that each submodule of a multiplication module over a regular ring is a multiplicative module. If A is a ring with commutative multiplication of right ideals, then each projective right ideal is a multiplicative module, and a finitely generated A-module M is a multiplicative module if and only if all its localizations with respect to maximal right ideals of A are cyclic modules over the corresponding localizations of A. In addition, several known results on multiplication modules over commutative rings are extended to modules over not necessarily commutative rings

  20. Multilevel Modulation formats for Optical Communication

    DEFF Research Database (Denmark)

    Jensen, Jesper Bevensee

    2008-01-01

    This thesis studies the use of multilevel modulation formats for optical communication systems. Multilevel modulation is an attractive method of increasing the spectral efficiency of optical communication systems. Various modulation formats employing phase modulation, amplitude modulation...... or a combination of the two have been studied. The use of polarization multiplexing (PolMux) to double the bit rate has also been investigated. The impact of transmission impairments such as chromatic dispersion, self phase modulation and cross phase modulation has been investigated. The feasibility of multilevel...... modulation for network oriented scenarios has been demonstrated....

  1. Photovoltaic Module Qualification Plus Testing

    Energy Technology Data Exchange (ETDEWEB)

    Kurtz, Sarah [National Renewable Energy Lab. (NREL), Golden, CO (United States); Wohlgemuth, John [National Renewable Energy Lab. (NREL), Golden, CO (United States); Kempe, Michael [National Renewable Energy Lab. (NREL), Golden, CO (United States); Bosco, Nick [National Renewable Energy Lab. (NREL), Golden, CO (United States); Hacke, Peter [National Renewable Energy Lab. (NREL), Golden, CO (United States); Jordan, Dirk [National Renewable Energy Lab. (NREL), Golden, CO (United States); Miller, David C. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Silverman, Timothy J. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Phillips, Nancy [3M Company, Maplewood, MN (United States); Earnest, Thomas [DuPont, Wilmington, DE (United States); Romero, Ralph [Black & Veatch, Overland Park, KS (United States)

    2013-12-01

    This report summarizes a set of test methods that are in the midst of being incorporated into IEC 61215 for certification of a module design or other tests that go beyond certification to establish bankability.

  2. Graphene based terahertz phase modulators

    Science.gov (United States)

    Kakenov, N.; Ergoktas, M. S.; Balci, O.; Kocabas, C.

    2018-07-01

    Electrical control of amplitude and phase of terahertz radiation (THz) is the key technological challenge for high resolution and noninvasive THz imaging. The lack of active materials and devices hinders the realization of these imaging systems. Here, we demonstrate an efficient terahertz phase and amplitude modulation using electrically tunable graphene devices. Our device structure consists of electrolyte-gated graphene placed at quarter wavelength distance from a reflecting metallic surface. In this geometry, graphene operates as a tunable impedance surface which yields electrically controlled reflection phase. Terahertz time domain reflection spectroscopy reveals the voltage controlled phase modulation of π and the reflection modulation of 50 dB. To show the promises of our approach, we demonstrate a multipixel phase modulator array which operates as a gradient impedance surface.

  3. Interfacial reactions in thermoelectric modules

    KAUST Repository

    Wu, Hsin-jay; Wu, Albert T.; Wei, Pei-chun; Chen, Sinn-wen

    2018-01-01

    Engineering transport properties of thermoelectric (TE) materials leads to incessantly breakthroughs in the zT values. Nevertheless, modular design holds a key factor to advance the TE technology. Herein, we discuss the structures of TE module

  4. Frequency-Modulation Correlation Spectrometer

    Science.gov (United States)

    Margolis, J. S.; Martonchik, J. V.

    1985-01-01

    New type of correlation spectrometer eliminates need to shift between two cells, one empty and one containing reference gas. Electrooptical phase modulator sinusoidally shift frequencies of sample transmission spectrum.

  5. An Embedded Reconfigurable Logic Module

    Science.gov (United States)

    Tucker, Jerry H.; Klenke, Robert H.; Shams, Qamar A. (Technical Monitor)

    2002-01-01

    A Miniature Embedded Reconfigurable Computer and Logic (MERCAL) module has been developed and verified. MERCAL was designed to be a general-purpose, universal module that that can provide significant hardware and software resources to meet the requirements of many of today's complex embedded applications. This is accomplished in the MERCAL module by combining a sub credit card size PC in a DIMM form factor with a XILINX Spartan I1 FPGA. The PC has the ability to download program files to the FPGA to configure it for different hardware functions and to transfer data to and from the FPGA via the PC's ISA bus during run time. The MERCAL module combines, in a compact package, the computational power of a 133 MHz PC with up to 150,000 gate equivalents of digital logic that can be reconfigured by software. The general architecture and functionality of the MERCAL hardware and system software are described.

  6. Modulational instability of coupled waves

    International Nuclear Information System (INIS)

    McKinstrie, C.J.; Bingham, R.

    1989-01-01

    The collinear propagation of an arbitrary number of finite-amplitude waves is modeled by a system of coupled nonlinear Schroedinger equations; one equation for each complex wave amplitude. In general, the waves are modulationally unstable with a maximal growth rate larger than the modulational growth rate of any wave alone. Moreover, waves that are modulationally stable by themselves can be driven unstable by the nonlinear coupling. The general theory is then applied to the relativistic modulational instability of two laser beams in a beat-wave accelerator. For parameters typical of a proposed beat-wave accelerator, this instability can seriously distort the incident laser pulse shapes on the particle-acceleration time scale, with detrimental consequences for particle acceleration

  7. Bigelow Expandable Activity Module Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The Bigelow Expandable Activity Module (BEAM) project is a NASA-industry partnership with Bigelow Aerospace (BA) that has developing the first human-rated expandable...

  8. US ITER limiter module design

    International Nuclear Information System (INIS)

    Mattas, R.F.; Billone, M.; Hassanein, A.

    1996-08-01

    The recent U.S. effort on the ITER (International Thermonuclear Experimental Reactor) shield has been focused on the limiter module design. This is a multi-disciplinary effort that covers design layout, fabrication, thermal hydraulics, materials evaluation, thermo- mechanical response, and predicted response during off-normal events. The results of design analyses are presented. Conclusions and recommendations are also presented concerning, the capability of the limiter modules to meet performance goals and to be fabricated within design specifications using existing technology

  9. Defining Modules, Modularity and Modularization

    DEFF Research Database (Denmark)

    Miller, Thomas Dedenroth; Pedersen, Per Erik Elgård

    The paper describes the evolution of the concept of modularity in a historical perspective. The main reasons for modularity are: create variety, utilize similarities, and reduce complexity. The paper defines the terms: Module, modularity, and modularization.......The paper describes the evolution of the concept of modularity in a historical perspective. The main reasons for modularity are: create variety, utilize similarities, and reduce complexity. The paper defines the terms: Module, modularity, and modularization....

  10. Laser modulator for LISA pathfinder

    Science.gov (United States)

    Voland, C.; Lund, G.; Coppoolse, W.; Crosby, P.; Stadler, M.; Kudielka, K.; Özkan, C.

    2017-11-01

    LISA Pathfinder is an ESA experiment to demonstrate the key technologies needed for the LISA mission to detect gravitational waves in space. The LISA Pathfinder spacecraft represents one arm of the LISA interferometer, containing an optical metrology system and two proof masses as inertial references for the drag-free control system. The LISA Pathfinder payload consists of two drag-free floating test masses located in the inertial sensors with their control electronics and an optical metrology subsystem. The optical metrology subsystem monitors the movement of both test masses relative to each other and to the spacecraft with very high sensitivity and resolution. This is achieved with a heterodyne Mach- Zehnder interferometer. This interferometer requires as input two coherent laser beams with a heterodyne frequency difference of a few kHz. To generate the two laser beams with a heterodyne frequency difference a Nd:YAG laser is used together with the Laser Modulator. The Nd:YAG laser generates a single coherent laser signal at a wavelength of 1064nm which is fibre coupled to the Laser Modulator. The Laser Modulator then generates the two optical beams with the required heterodyne frequency offset. In addition, the Laser Modulator is required to perform laser amplitude stabilization and optical path difference control for the two optical signals. The Laser Modulator consists of an optical unit - the LMU - and RF synthesiser, power amplification and control electronics. These electronics are all housed in the Laser Modulator Electronics (LME). The LMU has four primary functions: • Splitting of the input laser beam into two paths for later superposition in the interferometer. • Applying different frequency shifts to each of the beams. • Providing amplitude modulation control to each of the beams. • Providing active control of the optical path length difference between the two optical paths. The present paper describes the design and performance of the LMU

  11. Installing Python Modules with pip

    OpenAIRE

    Fred Gibbs

    2013-01-01

    This lesson shows you how to download and install Python modules. There are many ways to install external modules, but for the purposes of this lesson, we’re going to use a program called pip. As of Python 2.7.9 and newer, pip is installed by default. This tutorial will be helpful for anyone using older versions of Python (which are still quite common).

  12. Intelligent spacecraft module

    Science.gov (United States)

    Oungrinis, Konstantinos-Alketas; Liapi, Marianthi; Kelesidi, Anna; Gargalis, Leonidas; Telo, Marinela; Ntzoufras, Sotiris; Paschidi, Mariana

    2014-12-01

    The paper presents the development of an on-going research project that focuses on a human-centered design approach to habitable spacecraft modules. It focuses on the technical requirements and proposes approaches on how to achieve a spatial arrangement of the interior that addresses sufficiently the functional, physiological and psychosocial needs of the people living and working in such confined spaces that entail long-term environmental threats to human health and performance. Since the research perspective examines the issue from a qualitative point of view, it is based on establishing specific relationships between the built environment and its users, targeting people's bodily and psychological comfort as a measure toward a successful mission. This research has two basic branches, one examining the context of the system's operation and behavior and the other in the direction of identifying, experimenting and formulating the environment that successfully performs according to the desired context. The latter aspect is researched upon the construction of a scaled-model on which we run series of tests to identify the materiality, the geometry and the electronic infrastructure required. Guided by the principles of sensponsive architecture, the ISM research project explores the application of the necessary spatial arrangement and behavior for a user-centered, functional interior where the appropriate intelligent systems are based upon the existing mechanical and chemical support ones featured on space today, and especially on the ISS. The problem is set according to the characteristics presented at the Mars500 project, regarding the living quarters of six crew-members, along with their hygiene, leisure and eating areas. Transformable design techniques introduce spatial economy, adjustable zoning and increased efficiency within the interior, securing at the same time precise spatial orientation and character at any given time. The sensponsive configuration is

  13. Analyses of the mechanisms of amplitude modulation of aero-acoustic wind turbine sound

    DEFF Research Database (Denmark)

    Fischer, Andreas; Aagaard Madsen, Helge; Kragh, Knud Abildgaard

    2014-01-01

    This paper explores the source mechanism which cause amplitude modulation of the emitted sound of a wind turbine at large distances from the turbine, named as other amplitude modulation. Measurements of the fluctuating surface pressure on a 2.3MW wind turbine showed a considerable variation over...... give further evidence that transient stall is a main mechanism to cause other amplitude modulation. Wind shear was identified as a critical condition to cause angle of attack variations. Dierent control strategies to mitigate other amplitude modulation were proposed....

  14. Simulation research of acousto optic modulator drive based on Multisim

    Science.gov (United States)

    Wang, Shiqian; Guo, Yangkuan; Zhu, Lianqing; Na, Yunxiao; Zhang, Yinmin; Liu, Qianzhe

    2013-10-01

    The acousto optic modulator drive is mainly made with 2 amplitude shift keying (2ASK)circuit, pre-amplifier circuit and power operational amplifier circuit, and the simulation of the acousto optic modulator drive is realized. Firstly, the acousto optic modulator drive works as follows.The modulation function is realized by the analoged switch circuit, and the on-off of the analoged switch chip (CD4066) are controlled by the pulse signal generated by the electronic conversion circuit. The voltage amplification of the modulated signal is achieved by two reverse proportional operation implements voltage amplifier circuit, and the circuit is mainly made with the AD8001 chip. Then the amplified signal is transfered into a two-stage power operational amplifier circuit of class C which is mainly made with the chip of MRF158. Secondly, both of the simulating structures and the union debugging based on the designed system are realized by Multisim. Finally, obtaining the modulation signal of 150(MHz) frequency and 5(μs) pulse width illustrates that a 2ASk modulation of the 150 (MHz)carrier signal and the 20(kHz) modulation signal is achieved. Besides, as the frequency of input signal and amplitude of voltage change, the output power of the power operational amplifier circuit also changes, and the conclusion is drawn that the output power increases when the frequency of input signal decreases and the amplitude of voltage increases. The component selection of the drive's PCB design, the performance parameter and of the actual circuit and the debugging of the actual circuit are based on the simulation results.

  15. Wide-range voltage modulation

    International Nuclear Information System (INIS)

    Rust, K.R.; Wilson, J.M.

    1992-06-01

    The Superconducting Super Collider's Medium Energy Booster Abort (MEBA) kicker modulator will supply a current pulse to the abort magnets which deflect the proton beam from the MEB ring into a designated beam stop. The abort kicker will be used extensively during testing of the Low Energy Booster (LEB) and the MEB rings. When the Collider is in full operation, the MEBA kicker modulator will abort the MEB beam in the event of a malfunction during the filling process. The modulator must generate a 14-μs wide pulse with a rise time of less than 1 μs, including the delay and jitter times. It must also be able to deliver a current pulse to the magnet proportional to the beam energy at any time during ramp-up of the accelerator. Tracking the beam energy, which increases from 12 GeV at injection to 200 GeV at extraction, requires the modulator to operate over a wide range of voltages (4 kV to 80 kV). A vacuum spark gap and a thyratron have been chosen for test and evaluation as candidate switches for the abort modulator. Modulator design, switching time delay, jitter and pre-fire data are presented

  16. Research on modulated structure alloys

    International Nuclear Information System (INIS)

    Tsujimoto, Tokuzo; Saito, Kazuo; Hashimoto, Kenki

    1982-01-01

    Research was carried out for the purposes of clarifying the cause of modulated structure formation, developing the structure control method utilizing modulated structure and clarifying the suitability of modulated structure alloys as radiation damage-resisting materials. The research on structure control method encountered a difficulty in the analysis of experimental results, bu the following results were obtained in the other items. The method of solving a diffusion equation including a nonlinear term was found in course of the clarification of the cause of modulated structure formation. As a means of detecting faint unevenness in solid solution, of which the deviation of composition is a few %, the structure analysis method utilizing magnetic property was developed. This method was applied to Ni-9.6 at.% Ti alloy, and the process of expanding amplitude in composition variation in spinodal decomposition and the formation of solute atomshort region at the time of nucleation-growth were confirmed. Utilizing the high energy electron beam generated in a superhigh voltage electron microscope, electron beam irradiation experiment was carried out on precipitation hardening alloys with modulated structure. As the result, it was found that in Ni-Ti alloy, the amount of void swelling resistance showed the change with the increase of modulated structure period. (Kako, I.)

  17. Customized PEC modules. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Soerensen, Martin B. (DTI, Taastrup (Denmark))

    2012-07-01

    The purpose of the project ''Customized PEC modules'' was to move from the production hand-made individual DSCs (dye-sensitized solar cells) in the laboratory to the production of DSC modules in a semi-automated process. At the same time allowing sufficient variation in the product's specification for real tailoring of the product to the application. The tailoring can be related to the module's electrical output and size, but also to the possibility of designing patterns for decoration or communication purposes by playing around with the shape, size and layout of the individual cells forming the module. This was to be accomplished mainly by screen printing of DSC components on glass substrates at Mekoprint. For reaching this goal the work was divided into a number of steps. The central part of the work done was in the initial conception activity and the following manufacturing activity. An activity regarding optimization included several tasks of optimization and adaptation of the existing laboratory process for manufacturing of the DSCs. Finally, work focused on international activities was done. All the steps needed for the production of customized DSC modules have been demonstrated in this project. In combination with the development of a high performing printable sealant and sealing method all the prerequisites for producing customized DSC modules have been demonstrated. (LN)

  18. ITER Central Solenoid Module Fabrication

    Energy Technology Data Exchange (ETDEWEB)

    Smith, John [General Atomics, San Diego, CA (United States)

    2016-09-23

    The fabrication of the modules for the ITER Central Solenoid (CS) has started in a dedicated production facility located in Poway, California, USA. The necessary tools have been designed, built, installed, and tested in the facility to enable the start of production. The current schedule has first module fabrication completed in 2017, followed by testing and subsequent shipment to ITER. The Central Solenoid is a key component of the ITER tokamak providing the inductive voltage to initiate and sustain the plasma current and to position and shape the plasma. The design of the CS has been a collaborative effort between the US ITER Project Office (US ITER), the international ITER Organization (IO) and General Atomics (GA). GA’s responsibility includes: completing the fabrication design, developing and qualifying the fabrication processes and tools, and then completing the fabrication of the seven 110 tonne CS modules. The modules will be shipped separately to the ITER site, and then stacked and aligned in the Assembly Hall prior to insertion in the core of the ITER tokamak. A dedicated facility in Poway, California, USA has been established by GA to complete the fabrication of the seven modules. Infrastructure improvements included thick reinforced concrete floors, a diesel generator for backup power, along with, cranes for moving the tooling within the facility. The fabrication process for a single module requires approximately 22 months followed by five months of testing, which includes preliminary electrical testing followed by high current (48.5 kA) tests at 4.7K. The production of the seven modules is completed in a parallel fashion through ten process stations. The process stations have been designed and built with most stations having completed testing and qualification for carrying out the required fabrication processes. The final qualification step for each process station is achieved by the successful production of a prototype coil. Fabrication of the first

  19. Edexcel A2 Physics Student Unit Guide

    CERN Document Server

    Benn, Mike

    2010-01-01

    Student Unit Guides are perfect for revision. Each guide is written by an examiner and explains the unit requirements, summarises the relevant unit content and includes a series of specimen questions and answers. There are three sections to each guide:. Introduction - includes advice on how to use the guide, an explanation of the skills being tested by the assessment objectives, an outline of the unit or module and, depending on the unit, suggestions for how to revise effectively and prepare for the examination questions. Content Guidance - provides an examiner's overview of the module's key t

  20. AQA A2 Chemistry Student Unit Guide

    CERN Document Server

    Cross, Margaret

    2010-01-01

    Student Unit Guides are perfect for revision. Each guide is written by an examiner and explains the unit requirements, summarises the relevant unit content and includes a series of specimen questions and answers. There are three sections to each guide:. Introduction - includes advice on how to use the guide, an explanation of the skills being tested by the assessment objectives, an outline of the unit or module and, depending on the unit, suggestions for how to revise effectively and prepare for the examination questions. Content Guidance - provides an examiner's overview of the module's key t

  1. Adenosine A2A Receptor in the Monkey Basal Ganglia: Ultrastructural Localization and Colocalization With the Metabotropic Glutamate Receptor 5 in the Striatum

    OpenAIRE

    Bogenpohl, James W.; Ritter, Stefanie L.; Hall, Randy A.; Smith, Yoland

    2012-01-01

    The adenosine A2A receptor (A2AR) is a potential drug target for the treatment of Parkinson’s disease and other neurological disorders. In rodents, the therapeutic efficacy of A2AR modulation is improved by concomitant modulation of the metabotropic glutamate receptor 5 (mGluR5). To elucidate the anatomical substrate(s) through which these therapeutic benefits could be mediated, pre-embedding electron microscopy immunohistochemistry was used to conduct a detailed, quantitative ultrastructural...

  2. Module-theoretic properties of reachability modules for SRIQ

    CSIR Research Space (South Africa)

    Nortje, R

    2013-07-01

    Full Text Available ]. Definition 1. (Module for the arbitrary DL L) Let L be an arbitrary de- scription language, O an L ontology, and σ a statement formulated in L. Then, 2 O′ ⊆ O is a module for σ in O(a σ-module in O) whenever: O |= σ if and only if O′ |= σ. Definition 1... > 1, a SRIQ TBox T is in normal form if every axiom α ∈ T is in one of the following forms: α1: B1 u . . . uBn v C1 unionsq . . . unionsq Cm α2: D v C1 unionsq . . . unionsq Cm α3: B1 u . . . uBn v D α4: R1 ◦ . . . ◦Rn v Rn+1 α5: R1 v R2 α6: D1 v D2 α7...

  3. Laser frequency modulator for modulating a laser cavity

    Science.gov (United States)

    Erbert, Gaylen V.

    1992-01-01

    The present invention relates to a laser frequency modulator for modulating a laser cavity. It is known in the prior art to utilize a PZT (piezoelectric transducer) element in combination with a mirror to change the cavity length of a laser cavity (which changes the laser frequency). Using a PZT element to drive the mirror directly is adequate at frequencies below 10 kHz. However, in high frequency applications (100 kHz and higher) PZT elements alone do not provide a sufficient change in the cavity length. The present invention utilizes an ultrasonic concentrator with a PZT element and mirror to provide modulation of the laser cavity. With an ultrasonic concentrator, the mirror element at the end of a laser cavity can move at larger amplitudes and higher frequencies.

  4. Feasibility of photovoltaic: thermoelectric hybrid modules

    NARCIS (Netherlands)

    van Sark, W.G.J.H.M.|info:eu-repo/dai/nl/074628526

    2011-01-01

    Outdoor performance of photovoltaic (PV) modules suffers from elevated temperatures. Conversion efficiency losses of up to about 25% can result, depending on the type of integration of the modules in the roof. Cooling of modules would therefore enhance annual PV performance. Instead of module

  5. 47 CFR 74.663 - Modulation limits.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 4 2010-10-01 2010-10-01 false Modulation limits. 74.663 Section 74.663 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES EXPERIMENTAL RADIO... Stations § 74.663 Modulation limits. If amplitude modulation is employed, negative modulation peaks shall...

  6. Medical Terminology: Suffixes. Health Occupations Education Module.

    Science.gov (United States)

    Temple Univ., Philadelphia, PA. Div. of Vocational Education.

    This module on medical terminology (suffixes) is one of 17 modules designed for individualized instruction in health occupations education programs at both the secondary and postsecondary levels. This module consists of an introduction to the module topic, a list of resources needed, and three learning experiences. The first two learning…

  7. Low-cost solar module manufacturing

    International Nuclear Information System (INIS)

    Little, Roger G.; Nowlan, Michael J.; Matthei, Keith W.; Darkazalli, Ghazi

    1997-01-01

    As the market for terrestrial photovoltaic modules expands beyond the 80 MW per year level, module manufacturers are adopting a number of cost-reduction strategies, including the use of higher throughput equipment, increased process automation, and the fabrication of larger area cells and modules. This paper reviews recent activities at Spire Corporation in the development of advanced module manufacturing and testing equipment

  8. Health Occupations Module. The Integumentary System.

    Science.gov (United States)

    Temple Univ., Philadelphia, PA. Div. of Vocational Education.

    This module on the integumentary system is one of eight modules designed for individualized instruction in health occupations education programs at both the secondary and postsecondary levels. This module contains an introduction to the module topic, objectives (e.g., list and describe the types of glands formed in the skin, and explain the…

  9. Weakly distributive modules. Applications to supplement submodules

    Indian Academy of Sciences (India)

    Abstract. In this paper, we define and study weakly distributive modules as a proper generalization of distributive modules. We prove that, weakly distributive supplemented modules are amply supplemented. In a weakly distributive supplemented module every submodule has a unique coclosure. This generalizes a result of ...

  10. Whole Module Offgas Test Report: Space-X Dragon Module

    Science.gov (United States)

    James, John T.

    2012-01-01

    Between 7 April and 11 April 2012 a chemist from the JSC Toxicology Group acquired samples of air in 500 ml evacuated canisters from the sealed Dragon Module at the Space-X facility at KSC. Three samples were taken of facility air (two before the test and one after the test), and a total of 9 samples were taken from the sealed module in triplicate at the following times: 0 hours, 48 hours, and 96 hours. The module contained 470 kg, which was 100% of the mass to be launched. Analytical data contained in the Toxicology Group Report (attached) show that the ambient facility air was clean except for almost 9 milligrams per cubic meter of isopropanol (IPA) in the sample taken at the end of the test. Space-X must ensure that IPA is not introduced into the module before it is sealed for launch. Other minor contaminants in the ambient air included the following: perfluoro(2-methyl)pentane and hexamethylcyclotrisiloxane. The first-acquired samples of each triplicate from the module were not analyzed. Analyses of pairs of samples that were taken during the test show excellent agreement between the pairs and a linear increase in the T-values during the 4 days of the test (figure below). The rate of increase averaged 0.124 T units per day. If the time from last purge of the module on the ground to crew first entry on orbit is 10 days, then the T value at first entry should be less than 1.2 units, which is well below the criterion of 3.0 for consideration of additional protection of the crew from offgas products. The primary contributors were as follows: trimethylsilanol (0.057), fluorotrimethylsilane (0.047), acetaldehyde (0.004), hexamethylcyclopentasiloxane (0.003), and toluene (0.002).

  11. Steps in Modular Specifications for Concurrent Modules

    DEFF Research Database (Denmark)

    Da Rocha Pinto, Pedro; Dinsdale-Young, Thomas; Gardner, Philippa

    2015-01-01

    The specification of a concurrent program module is a difficult problem. The specifications must be strong enough to enable reasoning about the intended clients without reference to the underlying module implementation. We survey a range of verification techniques for specifying concurrent module......, in particular highlighting four key concepts: auxiliary state, interference abstraction, resource ownership and atomicity. We show how these concepts combine to provide powerful approaches to specifying concurrent modules.......The specification of a concurrent program module is a difficult problem. The specifications must be strong enough to enable reasoning about the intended clients without reference to the underlying module implementation. We survey a range of verification techniques for specifying concurrent modules...

  12. Photovoltaic cell module and method of forming

    Science.gov (United States)

    Howell, Malinda; Juen, Donnie; Ketola, Barry; Tomalia, Mary Kay

    2017-12-12

    A photovoltaic cell module, a photovoltaic array including at least two modules, and a method of forming the module are provided. The module includes a first outermost layer and a photovoltaic cell disposed on the first outermost layer. The module also includes a second outermost layer disposed on the photovoltaic cell and sandwiching the photovoltaic cell between the second outermost layer and the first outermost layer. The method of forming the module includes the steps of disposing the photovoltaic cell on the first outermost layer, disposing a silicone composition on the photovoltaic cell, and compressing the first outermost layer, the photovoltaic cell, and the second layer to form the photovoltaic cell module.

  13. A long pulse modulator for reduced size and cost

    International Nuclear Information System (INIS)

    Pfeffer, H.; Bartelson, L.; Bourkland, K.; Jensen, C.; Kerns, Q.; Prieto, P.; Saewert, G.; Wolff, D.

    1994-07-01

    A novel modulator has been designed, built and tested for the TESLA test facility. This e + e - accelerator concept uses superconducting RF cavities and requires 2ms of RF power at 10 pps. As the final accelerator will require several hundred modulators, a cost effective, space saving and high efficiency design is desired. This modulator used a modest size switched capacitor bank that droops approximately 20% during the pulse. This large droop is compensated for by the use of a resonant LC circuit. The capacitor bank is connected to the high side of a pulse transformer primary using a series GTO switch. The resonant circuit is connected to the low side of the pulse transformer primary. The output pulse is flat to within 1% for 1.9 ms during a 2.3 ms base pulse width. Measured efficiency, from breaker to klystron and including energy lost in the rise time, is approximately 85%

  14. Duobinary pulse shaping for frequency chirp enabled complex modulation.

    Science.gov (United States)

    Che, Di; Yuan, Feng; Khodakarami, Hamid; Shieh, William

    2016-09-01

    The frequency chirp of optical direct modulation (DM) used to be a performance barrier of optical transmission system, because it broadens the signal optical spectrum, which becomes more susceptible to chromatic dispersion induced inter-symbol interference (ISI). However, by considering the chirp as frequency modulation, the single DM simultaneously generates a 2-D signal containing the intensity and phase (namely, the time integral of frequency). This complex modulation concept significantly increases the optical signal to noise ratio (OSNR) sensitivity of DM systems. This Letter studies the duobinary pulse shaping (DB-PS) for chirp enabled DM and its impact on the optical bandwidth and system OSNR sensitivity. DB-PS relieves the bandwidth requirement, at the sacrifice of system OSNR sensitivity. As DB-PS induces a controlled ISI, the receiver requires one more tap for maximum likelihood sequence estimation (MLSE). We verify this modified MLSE with a 10-Gbaud duobinary PAM-4 transmission experiment.

  15. Photovoltaic module parameters acquisition model

    Energy Technology Data Exchange (ETDEWEB)

    Cibira, Gabriel, E-mail: cibira@lm.uniza.sk; Koščová, Marcela, E-mail: mkoscova@lm.uniza.sk

    2014-09-01

    Highlights: • Photovoltaic five-parameter model is proposed using Matlab{sup ®} and Simulink. • The model acquisits input sparse data matrix from stigmatic measurement. • Computer simulations lead to continuous I–V and P–V characteristics. • Extrapolated I–V and P–V characteristics are in hand. • The model allows us to predict photovoltaics exploitation in different conditions. - Abstract: This paper presents basic procedures for photovoltaic (PV) module parameters acquisition using MATLAB and Simulink modelling. In first step, MATLAB and Simulink theoretical model are set to calculate I–V and P–V characteristics for PV module based on equivalent electrical circuit. Then, limited I–V data string is obtained from examined PV module using standard measurement equipment at standard irradiation and temperature conditions and stated into MATLAB data matrix as a reference model. Next, the theoretical model is optimized to keep-up with the reference model and to learn its basic parameters relations, over sparse data matrix. Finally, PV module parameters are deliverable for acquisition at different realistic irradiation, temperature conditions as well as series resistance. Besides of output power characteristics and efficiency calculation for PV module or system, proposed model validates computing statistical deviation compared to reference model.

  16. NEMS integrating module documentation report

    Energy Technology Data Exchange (ETDEWEB)

    1993-12-14

    The National Energy Modeling System (NEMS) is a computer modeling system that produces a general equilibrium solution for energy supply and demand in the US energy markets. The model achieves a supply and demand balance in the end-use demand regions, defined as the nine Census Divisions, by solving for the prices of each energy type such that the quantities producers are willing to supply equal the quantities consumers wish to consume. The system reflects market economics, industry structure, and energy policies and regulations that influence market behavior. The NEMS Integrating Module is the central integrating component of a complex modeling system. As such, a thorough understanding of its role in the modeling process can only be achieved by placing it in the proper context with respect to the other modules. To that end, this document provides an overview of the complete NEMS model, and includes brief descriptions of the modules with which the Integrating Module interacts. The emphasis and focus, however, is on the structure and function of the Integrating Module of NEMS.

  17. Photovoltaic module parameters acquisition model

    International Nuclear Information System (INIS)

    Cibira, Gabriel; Koščová, Marcela

    2014-01-01

    Highlights: • Photovoltaic five-parameter model is proposed using Matlab ® and Simulink. • The model acquisits input sparse data matrix from stigmatic measurement. • Computer simulations lead to continuous I–V and P–V characteristics. • Extrapolated I–V and P–V characteristics are in hand. • The model allows us to predict photovoltaics exploitation in different conditions. - Abstract: This paper presents basic procedures for photovoltaic (PV) module parameters acquisition using MATLAB and Simulink modelling. In first step, MATLAB and Simulink theoretical model are set to calculate I–V and P–V characteristics for PV module based on equivalent electrical circuit. Then, limited I–V data string is obtained from examined PV module using standard measurement equipment at standard irradiation and temperature conditions and stated into MATLAB data matrix as a reference model. Next, the theoretical model is optimized to keep-up with the reference model and to learn its basic parameters relations, over sparse data matrix. Finally, PV module parameters are deliverable for acquisition at different realistic irradiation, temperature conditions as well as series resistance. Besides of output power characteristics and efficiency calculation for PV module or system, proposed model validates computing statistical deviation compared to reference model

  18. Glutathione S-transferase M1 and T1, CYP1A2-2467T/delT ...

    African Journals Online (AJOL)

    The present study investigated the impact of metabolic gene polymorphisms in modulating lung cancer risk susceptibility. Gene polymorphisms encoding Cytochrome 1A2 (CYP1A2) and Glutathione-S-transferases (GSTT1 and GSTM1) are involved in the bioactivation and detoxification of tobacco carcinogens and may ...

  19. Command and Service Module Communications

    Science.gov (United States)

    Interbartolo, Michael

    2009-01-01

    This viewgraph presentation examines Command and Service Module (CSM) Communications. The communication system's capabilities are defined, including CSM-Earth, CSM-Lunar Module and CSM-Extravehicular crewman communications. An overview is provided for S-band communications, including data transmission and receiving rates, operating frequencies and major system components (pre-modulation processors, unified S-band electronics, S-band power amplifier and S-band antennas). Additionally, data transmission rates, operating frequencies and the capabilities of VHF communications are described. Major VHF components, including transmitters and receivers, and the VHF multiplexer and antennas are also highlighted. Finally, communications during pre-launch, ascent, in-flight and entry are discussed. Overall, the CSM communication system was rated highly by flight controllers and crew. The system was mostly autonomous for both crew and flight controllers and no major issues were encountered during flight.

  20. Progress of MICE RFCC Module

    Energy Technology Data Exchange (ETDEWEB)

    Li, D.; Bowring, D.; DeMello, A.; Gourlay, S.; Green, M.; Li, N.; Niinikoski, T.; Pan, H.; Prestemon, S.; Virostek, S.; Zisman, M.; Bross, A.; Carcagno, R.; Kashikhin, V.; Sylvester, C.; Chen, A. B.; Guo, Bin; Li, Liyi; Xu, Fengyu; Cao, Y.; Sun, S.; Wang, Li; Yin, Lixin; Luo, Tianhuan; Summers, Don; Smith, B.; Radovinsky, A.; Zhukovsky, A.; Kaplan, D.

    2012-05-20

    Recent progress on the design and fabrication of the RFCC (RF and superconducting Coupling Coil) module for the international MICE (Muon Ionization Cooling Experiment) are reported. The MICE ionization cooling channel has two RFCC modules, each having four 201- MHz normal conducting RF cavities surrounded by one superconducting coupling coil (solenoid) magnet. The magnet is designed to be cooled by three cryocoolers. Fabrication of the RF cavities is complete; preparation for the cavity electro-polishing, low power RF measurements, and tuning are in progress at Lawrence Berkeley National Laboratory (LBNL). Fabrication of the cold mass of the first coupling coil magnet has been completed in China and the cold mass arrived at LBNL in late 2011. Preparations for testing the cold mass are currently under way at Fermilab. Plans for the RFCC module assembly and integration are being developed and are described.

  1. Active combustion flow modulation valve

    Science.gov (United States)

    Hensel, John Peter; Black, Nathaniel; Thorton, Jimmy Dean; Vipperman, Jeffrey Stuart; Lambeth, David N; Clark, William W

    2013-09-24

    A flow modulation valve has a slidably translating hollow armature with at least one energizable coil wound around and fixably attached to the hollow armature. The energizable coil or coils are influenced by at least one permanent magnet surrounding the hollow armature and supported by an outer casing. Lorentz forces on the energizable coils which are translated to the hollow armature, increase or decrease the flow area to provide flow throttling action. The extent of hollow armature translation depends on the value of current supplied and the direction of translation depends on the direction of current flow. The compact nature of the flow modulation valve combined with the high forces afforded by the actuator design provide a flow modulation valve which is highly responsive to high-rate input control signals.

  2. Acoustic field modulation in regenerators

    Science.gov (United States)

    Hu, J. Y.; Wang, W.; Luo, E. C.; Chen, Y. Y.

    2016-12-01

    The regenerator is a key component that transfers energy between heat and work. The conversion efficiency is significantly influenced by the acoustic field in the regenerator. Much effort has been spent to quantitatively determine this influence, but few comprehensive experimental verifications have been performed because of difficulties in modulating and measuring the acoustic field. In this paper, a method requiring two compressors is introduced and theoretically investigated that achieves acoustic field modulation in the regenerator. One compressor outputs the acoustic power for the regenerator; the other acts as a phase shifter. A RC load dissipates the acoustic power out of both the regenerator and the latter compressor. The acoustic field can be modulated by adjusting the current in the two compressors and opening the RC load. The acoustic field is measured with pressure sensors instead of flow-field imaging equipment, thereby greatly simplifying the experiment.

  3. Unity connecting module in SSPF

    Science.gov (United States)

    1998-01-01

    In the Space Station Processing Facility, the Unity connecting module, part of the International Space Station, is shown with Pressurized Mating Adapters 1 (left) and 2 (right) attached. Unity is scheduled to undergo testing of the common berthing mechanism to which other space station elements will dock. Unity is the primary payload on mission STS-88, targeted to launch Dec. 3, 1998. Other testing includes the Pad Demonstration Test to verify the compatibility of the module with the Space Shuttle as well as the ability of the astronauts to send and receive commands to Unity from the flight deck of the orbiter. Unity is expected to be ready for installation into the payload canister on Oct. 25, and transported to Launch Pad 39-A on Oct. 27. The Unity will be mated to the Russian-built Zarya control module which should already be in orbit at that time.

  4. Solid-state membrane module

    Science.gov (United States)

    Gordon, John Howard [Salt Lake City, UT; Taylor, Dale M [Murray, UT

    2011-06-07

    Solid-state membrane modules comprising at least one membrane unit, where the membrane unit has a dense mixed conducting oxide layer, and at least one conduit or manifold wherein the conduit or manifold comprises a dense layer and at least one of a porous layer and a slotted layer contiguous with the dense layer. The solid-state membrane modules may be used to carry out a variety of processes including the separating of any ionizable component from a feedstream wherein such ionizable component is capable of being transported through a dense mixed conducting oxide layer of the membrane units making up the membrane modules. For ease of construction, the membrane units may be planar.

  5. Detector module for gas monitor

    International Nuclear Information System (INIS)

    1980-01-01

    The invention relates to radioactive source detector module for use in a gas monitor. It is adapted to contain the source and other detector components to allow sealed coupling of those components with other portions of the gas monitor. It is particularly concerned with the use of radioactive materials used as electron sources in gas monitors. The module is used to detect changes in electron flow caused by partial absorption of the electron capture gas flowing between two electrodes. The assembly includes a gas flow source, a gas receiver and an electronic assembly for receiving a signal from the detector. The radioactive source and electrodes are housed so that they are connected to the gas flow source so as to prevent accidental or undesired disconnection. It is designed so that the detector module may be removed or replaced into the gas monitor assemblies by untrained personnel so as to prevent exposure to the radioactive material. Full details are given. (U.K.)

  6. Interfacial reactions in thermoelectric modules

    KAUST Repository

    Wu, Hsin-jay

    2018-02-21

    Engineering transport properties of thermoelectric (TE) materials leads to incessantly breakthroughs in the zT values. Nevertheless, modular design holds a key factor to advance the TE technology. Herein, we discuss the structures of TE module and illustrate the inter-diffusions across the interface of constituent layers. For Bi2Te3-based module, soldering is the primary bonding method, giving rise to the investigations on the selections of solder, diffusion barrier layer and electrode. For mid-temperature PbTe-based TE module, hot-pressing or spark plasma sintering are alternative bonding approaches; the inter-diffusions between the diffusion barrier layer, electrode and TE substrate are addressed as well.

  7. Allosteric mechanisms within the adenosine A2A-dopamine D2 receptor heterotetramer

    Science.gov (United States)

    Ferré, Sergi; Bonaventura, Jordi; Tomasi, Dardo; Navarro, Gemma; Moreno, Estefanía; Cortés, Antonio; Lluís, Carme; Casadó, Vicent; Volkow, Nora D.

    2017-01-01

    The structure constituted by a G protein coupled receptor (GPCR) homodimer and a G protein provides a main functional unit and oligomeric entities can be viewed as multiples of dimers. For GPCR heteromers, experimental evidence supports a tetrameric structure, comprised of two different homodimers, each able to signal with its preferred G protein. GPCR homomers and heteromers can act as the conduit of allosteric interactions between orthosteric ligands. The well-known agonist/agonist allosteric interaction in the adenosine A2A receptor (A2AR)-dopamine D2 receptor (D2R) heteromer, by which A2AR agonists decrease the affinity of D2R agonists, gave the first rationale for the use of A2AR antagonists in Parkinson’s disease. We review new pharmacological findings that can be explained in the frame of a tetrameric structure of the A2AR-D2R heteromer: first, ligand-independent allosteric modulations by the D2R that result in changes of the binding properties of A2AR ligands; second, differential modulation of the intrinsic efficacy of D2R ligands for G protein-dependent and independent signaling; third, the canonical antagonistic Gs-Gi interaction within the frame of the heteromer; and fourth, the ability of A2AR antagonists, including caffeine, to also exert the same allosteric modulations of D2R ligands than A2AR agonists, while A2AR agonists and antagonists counteract each other’s effects. These findings can have important clinical implications when evaluating the use of A2AR antagonists. They also call for the need of monitoring caffeine intake when evaluating the effect of D2R ligands, when used as therapeutic agents in neuropsychiatric disorders or as probes in imaging studies. PMID:26051403

  8. The adenosine A2A receptor — Myocardial protectant and coronary target in endotoxemia

    Science.gov (United States)

    Reichelt, Melissa E.; Ashton, Kevin J.; Tan, Xing Lin; Mustafa, S. Jamal; Ledent, Catherine; Delbridge, Lea M.D.; Hofmann, Polly A.; Headrick, John P.; Morrison, R. Ray

    2013-01-01

    Background Cardiac injury and dysfunction are contributors to disease progression and mortality in sepsis. This study evaluated the cardiovascular role of intrinsic A2A adenosine receptor (A2AAR) activity during lipopolysaccharide (LPS)-induced inflammation. Methods We assessed the impact of 24 h of LPS challenge (20 mg/kg, IP) on cardiac injury, coronary function and inflammatory mediator levels in Wild-Type (WT) mice and mice lacking functional A2AARs (A2AAR KO). Results Cardiac injury was evident in LPS-treated WTs, with ∼7-fold elevation in serum cardiac troponin I (cTnI), and significant ventricular and coronary dysfunction. Absence of A2AARs increased LPS-provoked cTnI release at 24 h by 3-fold without additional demise of contraction function. Importantly, A2AAR deletion per se emulated detrimental effects of LPS on coronary function, and LPS was without effect in coronary vessels lacking A2AARs. Effects of A2AAR KO were independent of major shifts in circulating C-reactive protein (CRP) and haptoglobin. Cytokine responses were largely insensitive to A2AAR deletion; substantial LPS-induced elevations (up to 100-fold) in IFN-γ and IL-10 were unaltered in A2AAR KO mice, as were levels of IL-4 and TNF-α. However, late elevations in IL-2 and IL-5 were differentially modulated by A2AAR KO (IL-2 reduced, IL-5 increased). Data demonstrate that in the context of LPS-triggered cardiac and coronary injury, A2AAR activity protects myocardial viability without modifying contractile dysfunction, and selectively modulates cytokine (IL-2, IL-5) release. A2AARs also appear to be targeted by LPS in the coronary vasculature. Conclusions These experimental data suggest that preservation of A2AAR functionality might provide therapeutic benefit in human sepsis. PMID:22192288

  9. Thermal management, systems and modules; Thermomanagement, Systeme und Module

    Energy Technology Data Exchange (ETDEWEB)

    Flik, M. [Behr GmbH und Co., Stuttgart (Germany)

    1999-11-01

    Up till now the individual systems for engine temperature control and air conditioning of the vehicle cabin have to a large extent been viewed independently of one another. With the progress of electronic control systems, however, Behr has adopted an integrative approach to managing all heat and substance flows outside of the engine. This perspective, which is known as thermal management, has significantly boosted the rate of innovation. In a short period of time, new and optimized modules and systems have allowed considerable improvements to be made in relation to passenger comfort and safety, the integration of subsystems and modules into the vehicle and environmental compatibility. This innovation drive, which also extends to the design of major modules, will continue to gain impetus in the future. (orig.) [German] Bisher wurden die verschiedenen Systeme zur Temperierung des Motors und zur Klimatisierung der Fahrzeugkabine weitgehend unabhaengig voneinander betrachtet. Mit dem Vordringen der elektronischen Regelung hat bei Behr jedoch eine gesamtheitliche Betrachtung aller Waerme- und Stoffstroeme ausserhalb des Motors eingesetzt. Diese Sichtweise, Thermomanagement genannt, hat eine erhebliche Innovationsdynamik ermoeglicht. Mit neuen und optimierten Modulen und Systemen konnten in kurzer Zeit betraechtliche Verbesserungen erzielt werden - bei Komfort und Sicherheit der Fahrzeuginsassen, bei der Integration der Subsysteme und Module ins Fahrzeug sowie bei seiner oekologischen Vertraeglichkeit. Diese Innovationsdynamik, die auch die Bildung von Grossmodulen einschliesst, wird in Zukunft noch zunehmen. (orig.)

  10. Static feed water electrolysis module

    Science.gov (United States)

    Powell, J. D.; Schubert, F. H.; Jensen, F. C.

    1974-01-01

    An advanced static feed water electrolysis module (SFWEM) and associated instrumentation for generating breathable O2 was developed. The system also generates a H2 byproduct for use in an air revitalization system for O2 recovery from metabolic CO2. Special attention was given to: (1) eliminating water feed compartment degassing, (2) eliminating need for zero gravity condenser/separators, (3) increasing current density capability, and (4) providing a self contained module so that operation is independent of laboratory instrumentation and complicated startup/shutdown procedures.

  11. DELPHI Barrel Muon Chamber Module

    CERN Multimedia

    1989-01-01

    The module was used as part of the muon identification system on the barrel of the DELPHI detector at LEP, and was in active use from 1989 to 2000. The module consists of 7 individual muons chambers arranged in 2 layers. Chambers in the upper layer are staggered by half a chamber width with respect to the lower layer. Each individual chamber is a drift chamber consisting of an anode wire, 47 microns in diameter, and a wrapped copper delay line. Each chamber provided 3 signal for each muon passing through the chamber, from which a 3D space-point could be reconstructed.

  12. Transparent solar cell window module

    Energy Technology Data Exchange (ETDEWEB)

    Chau, Joseph Lik Hang; Chen, Ruei-Tang; Hwang, Gan-Lin; Tsai, Ping-Yuan [Nanopowder and Thin Film Technology Center, ITRI South, Industrial Technology Research Institute, Tainan County 709 (China); Lin, Chien-Chu [I-Lai Acrylic Corporation, Tainan City (China)

    2010-03-15

    A transparent solar cell window module based on the integration of traditional silicon solar cells and organic-inorganic nanocomposite material was designed and fabricated. The transparent solar cell window module was composed of a nanocomposite light-guide plate and traditional silicon solar cells. The preparation of the nanocomposite light-guide plate is easy without modification of the traditional casting process, the nanoparticles sol can be added directly to the polymethyl methacrylate (PMMA) monomer syrup during the process. The solar energy collected by this window can be used to power up small household electrical appliances. (author)

  13. Nonlinear modulation of ionization waves

    International Nuclear Information System (INIS)

    Bekki, Naoaki

    1981-01-01

    In order to investigate the nonlinear characteristics of ionization waves (moving-striations) in the positive column of glow discharge, a nonlinear modulation of ionization waves in the region of the Pupp critical current is analysed by means of the reductive perturbation method. The modulation of ionization waves is described by a nonlinear Schroedinger type equation. The coefficients of the equation are evaluated using the data of the low pressure Argon-discharge, and the simple solutions (plane wave and envelope soliton type solutions) are presented. Under a certain condition an envelope soliton is propagated through the positive column. (author)

  14. 18 CFR 3a.2 - Authority.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Authority. 3a.2 Section 3a.2 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES NATIONAL SECURITY INFORMATION General § 3a.2 Authority. Official information or...

  15. Development and Evaluation of a 2KVA Inverter

    Directory of Open Access Journals (Sweden)

    Ajayi Adedayo

    2013-09-01

    Full Text Available A 2KV inverter was designed, developed and tested for household applications. It consists of a heavy duty (24 V, 80 AH, oscillator unit, PWM (Pulse-width modulation controller unit, driver unit, amplifier unit, center-tap step up transformer and battery charger unit. The battery powered the circuitry and the oscillator section generates the drive signal that is amplified and set up the transformer to produce 240 V supply at the secondary winding connected to the output socket of inverter. The feedback control circuit uses discrete components such as: full wave rectifier, pulse width modulator (IC, diodes and other components to sense the output voltage (or load current. When the feedback senses that the load on the inverter output has increased, the inverter control circuitry acts by increasing the width of the switching pulse in the oscillator section which turn on the MOSFETS. MOSFETS turns on for longer time each cycle, automatically correcting the R.M.S value of the output to compensate for any drop in peak-peak output voltage as well as continuous charging of battery, consequently, maintaining a steady output voltage level in inverter irrespective of the load characteristics. The outputs of the tests carried on the unit shows that that instrument performs satisfactory well.

  16. Coherent states on Hilbert modules

    International Nuclear Information System (INIS)

    Ali, S Twareque; Bhattacharyya, T; Roy, S S

    2011-01-01

    We generalize the concept of coherent states, traditionally defined as special families of vectors on Hilbert spaces, to Hilbert modules. We show that Hilbert modules over C*-algebras are the natural settings for a generalization of coherent states defined on Hilbert spaces. We consider those Hilbert C*-modules which have a natural left action from another C*-algebra, say A. The coherent states are well defined in this case and they behave well with respect to the left action by A. Certain classical objects like the Cuntz algebra are related to specific examples of coherent states. Finally we show that coherent states on modules give rise to a completely positive definite kernel between two C*-algebras, in complete analogy to the Hilbert space situation. Related to this, there is a dilation result for positive operator-valued measures, in the sense of Naimark. A number of examples are worked out to illustrate the theory. Some possible physical applications are also mentioned.

  17. Adolescence Education: Physical Aspect, Module One; Social Aspects, Module Two; Sex Roles, Module Three; Sexually Transmitted Diseases, Module Four.

    Science.gov (United States)

    United Nations Educational, Scientific and Cultural Organization, Bangkok (Thailand). Principal Regional Office for Asia and the Pacific.

    Adolescence Education is a family life education training program designed to assist young people in their physical, social, emotional, and moral development as they prepare for adulthood, marriage, parenthood, aging, and social relationships in the context of family and society. This package consists of four individually bound modules: (1)…

  18. WRAP module 1 treatment plan

    International Nuclear Information System (INIS)

    Mayancsik, B.A.

    1995-05-01

    This document provides the methodology to treat waste in the Waste Receiving and Processing Module 1 facility to meet the Resource Conservation and Recovery Act (RCRA) land disposal restrictions or the Waste Isolation and Pilot Plant waste acceptance criteria. This includes Low-Level Mixed Waste, Transuranic Waste, and Transuranic Mixed Waste

  19. The Knife Machine. Module 15.

    Science.gov (United States)

    South Carolina State Dept. of Education, Columbia. Office of Vocational Education.

    This module on the knife machine, one in a series dealing with industrial sewing machines, their attachments, and operation, covers one topic: performing special operations on the knife machine (a single needle or multi-needle machine which sews and cuts at the same time). These components are provided: an introduction, directions, an objective,…

  20. The Blindstitch Machine. Module 11.

    Science.gov (United States)

    South Carolina State Dept. of Education, Columbia. Office of Vocational Education.

    This module on the purpose and use of the blindstitch machine, one in a series on clothing construction for industrial sewing machine operators designed for student self-study, contains three sections. Each section includes the following parts: an introduction, directions, an objective, learning activities, student information, student self-check,…

  1. The Chainstitch Machine. Module 18.

    Science.gov (United States)

    South Carolina State Dept. of Education, Columbia. Office of Vocational Education.

    This module on the chainstitch machine, one in a series dealing with industrial sewing machines, their attachments, and operation, covers one topic: performing special operations on the chainstitch machine. These components are provided: an introduction, directions, an objective, learning activities, student information, a student self-check, and…

  2. Radio frequency modulation made easy

    CERN Document Server

    Faruque, Saleh

    2017-01-01

    This book introduces Radio Frequency Modulation to a broad audience. The author blends theory and practice to bring readers up-to-date in key concepts, underlying principles and practical applications of wireless communications. The presentation is designed to be easily accessible, minimizing mathematics and maximizing visuals.

  3. Bidirectional reachability-based modules

    CSIR Research Space (South Africa)

    Nortje, R

    2011-07-01

    Full Text Available The authors introduce an algorithm for MinA extraction in EL based on bidirectional reachability. They obtain a significant reduction in the size of modules extracted at almost no additional cost to that of extracting standard reachability...

  4. Rights & Responsibilities. Personnel Management Module.

    Science.gov (United States)

    Barker, Gale; And Others

    This module on rights and responsibilities is intended to introduce the hospitality manager or supervisor to sound personnel management practices that comply with the law. The material is presented in a self-instructional format in seven sections. At the beginning of each section is a statement of the objectives that will be achieved as a result…

  5. Market Segmentation: An Instructional Module.

    Science.gov (United States)

    Wright, Peter H.

    A concept-based introduction to market segmentation is provided in this instructional module for undergraduate and graduate transportation-related courses. The material can be used in many disciplines including engineering, business, marketing, and technology. The concept of market segmentation is primarily a transportation planning technique by…

  6. Can Arousal Modulate Response Inhibition?

    Science.gov (United States)

    Weinbach, Noam; Kalanthroff, Eyal; Avnit, Amir; Henik, Avishai

    2015-01-01

    The goal of the present study was to examine if and how arousal can modulate response inhibition. Two competing hypotheses can be drawn from previous literature. One holds that alerting cues that elevate arousal should result in an impulsive response and therefore impair response inhibition. The other suggests that alerting enhances processing of…

  7. Apollo 11 Command Service Module

    Science.gov (United States)

    1969-01-01

    A close-up view of the Apollo 11 command service module ready to be mated with the spacecraft LEM adapter of the third stage. The towering 363-foot Saturn V was a multi-stage, multi-engine launch vehicle standing taller than the Statue of Liberty. Altogether, the Saturn V engines produced as much power as 85 Hoover Dams.

  8. Exercises in modules and rings

    CERN Document Server

    Lam, TY

    2009-01-01

    This volume offers a compendium of exercises of varying degree of difficulty in the theory of modules and rings. All exercises are solved in full detail. Each section begins with an introduction giving the general background and the theoretical basis for the problems that follow.

  9. The Buttonhole Machine. Module 13.

    Science.gov (United States)

    South Carolina State Dept. of Education, Columbia. Office of Vocational Education.

    This module on the bottonhole machine, one in a series dealing with industrial sewing machines, their attachments, and operation, covers two topics: performing special operations on the buttonhole machine (parts and purpose) and performing special operations on the buttonhole machine (gauged buttonholes). For each topic these components are…

  10. Transportation Brokerage: An Instructional Module.

    Science.gov (United States)

    Hayden, Linda

    A concept-based introduction to transportation brokerage is provided in this instructional module for undergraduate and graduate transportation-related courses for disciplines such as engineering, business, marketing, and technology. The concept of transportation brokerage is defined as an assignment of the management of a specific element of a…

  11. Attention modulates visual size adaptation.

    Science.gov (United States)

    Kreutzer, Sylvia; Fink, Gereon R; Weidner, Ralph

    2015-01-01

    The current study determined in healthy subjects (n = 16) whether size adaptation occurs at early, i.e., preattentive, levels of processing or whether higher cognitive processes such as attention can modulate the illusion. To investigate this issue, bottom-up stimulation was kept constant across conditions by using a single adaptation display containing both small and large adapter stimuli. Subjects' attention was directed to either the large or small adapter stimulus by means of a luminance detection task. When attention was directed toward the small as compared to the large adapter, the perceived size of the subsequent target was significantly increased. Data suggest that different size adaptation effects can be induced by one and the same stimulus depending on the current allocation of attention. This indicates that size adaptation is subject to attentional modulation. These findings are in line with previous research showing that transient as well as sustained attention modulates visual features, such as contrast sensitivity and spatial frequency, and influences adaptation in other contexts, such as motion adaptation (Alais & Blake, 1999; Lankheet & Verstraten, 1995). Based on a recently suggested model (Pooresmaeili, Arrighi, Biagi, & Morrone, 2013), according to which perceptual adaptation is based on local excitation and inhibition in V1, we conclude that guiding attention can boost these local processes in one or the other direction by increasing the weight of the attended adapter. In sum, perceptual adaptation, although reflected in changes of neural activity at early levels (as shown in the aforementioned study), is nevertheless subject to higher-order modulation.

  12. Perl Modules for Constructing Iterators

    Science.gov (United States)

    Tilmes, Curt

    2009-01-01

    The Iterator Perl Module provides a general-purpose framework for constructing iterator objects within Perl, and a standard API for interacting with those objects. Iterators are an object-oriented design pattern where a description of a series of values is used in a constructor. Subsequent queries can request values in that series. These Perl modules build on the standard Iterator framework and provide iterators for some other types of values. Iterator::DateTime constructs iterators from DateTime objects or Date::Parse descriptions and ICal/RFC 2445 style re-currence descriptions. It supports a variety of input parameters, including a start to the sequence, an end to the sequence, an Ical/RFC 2445 recurrence describing the frequency of the values in the series, and a format description that can refine the presentation manner of the DateTime. Iterator::String constructs iterators from string representations. This module is useful in contexts where the API consists of supplying a string and getting back an iterator where the specific iteration desired is opaque to the caller. It is of particular value to the Iterator::Hash module which provides nested iterations. Iterator::Hash constructs iterators from Perl hashes that can include multiple iterators. The constructed iterators will return all the permutations of the iterations of the hash by nested iteration of embedded iterators. A hash simply includes a set of keys mapped to values. It is a very common data structure used throughout Perl programming. The Iterator:: Hash module allows a hash to include strings defining iterators (parsed and dispatched with Iterator::String) that are used to construct an overall series of hash values.

  13. Reliability and Energy Output of Bifacial Modules

    Energy Technology Data Exchange (ETDEWEB)

    Van Aken, B.B.; Jansen, M.J.; Dekker, N.J.J. [ECN Solar Energy, Petten (Netherlands)

    2013-06-15

    Although flash tests under standard test conditions yields lower power due to transmittance of the back sheet, bifacial modules are expected to outperform their monofacial equivalents in terms of yearly energy output in the field. We compare flash tests for bifacial modules with and without a light scattering panel directly behind the modules: 3% more power output is obtained. We also report on the damp-heat reliability of modules with transparent back sheet. Finally we will present the results of an outdoor study comparing modules with transparent back sheet and modules with state-of-the-art AR coating on the front glass.

  14. Spring-cleaning at the solar module; Fruehjahrsputz am Modul

    Energy Technology Data Exchange (ETDEWEB)

    Orben, Steffen [Orben Wasseraufbereitung, Wiesbaden (Germany)

    2013-04-15

    The solar power yield of a photovoltaic power plant can be reduced significantly by a natural pollution. The average loss in performance and yield at mild and moderate surface contaminations is between eight and sixteen percent. The self-cleaning effect due to wind, rain and snow is not sufficient in order to purify the solar panels. In contrast, the purification with desalinated water receives the performance of solar generators and ensures the yields. Desalinated water can be produced from tap water by reverse osmosis and ion exchange. The water consumption amounts ten liters for a performance of one kilowatt of the solar module. Other important factors are 0.23 Euro for a filter cartridge as well as 11.50 Euro for personnel costs for a performance of one kilowatt of the solar module.

  15. Structural modules in AP1000 plant design

    International Nuclear Information System (INIS)

    Prasad, N.; Tunon-Sanjur, L.

    2007-01-01

    Structural modules are extensively used in AP1000 plant design. The shop manufacturing of modules components improves the quality and reliability of plant structures. The application of modules has a positive impact on construction schedules, and results in substantial savings in the construction cost. This paper describes various types of structural modules used for AP1000 plant structures. CA structural wall modules are steel plate modules with concrete placed, on or within the module, after module installation. The layout and design of the largest CA wall modules, CA01 and CA20, is described in detail. General discussion of structural floor modules, such as the composite and finned floors, is also included. Steel form CB modules (liners) consist of plate reinforced with angle stiffeners and tee sections. The angles and the tee sections are on the concrete side of the plate. Design of CB20 has been included as an example of CB type modules. Design codes and structural concepts related to module designs are discussed. (authors)

  16. Earth System Science Education Modules

    Science.gov (United States)

    Hall, C.; Kaufman, C.; Humphreys, R. R.; Colgan, M. W.

    2009-12-01

    The College of Charleston is developing several new geoscience-based education modules for integration into the Earth System Science Education Alliance (ESSEA). These three new modules provide opportunities for science and pre-service education students to participate in inquiry-based, data-driven experiences. The three new modules will be discussed in this session. Coastal Crisis is a module that analyzes rapidly changing coastlines and uses technology - remotely sensed data and geographic information systems (GIS) to delineate, understand and monitor changes in coastal environments. The beaches near Charleston, SC are undergoing erosion and therefore are used as examples of rapidly changing coastlines. Students will use real data from NASA, NOAA and other federal agencies in the classroom to study coastal change. Through this case study, learners will acquire remotely sensed images and GIS data sets from online sources, utilize those data sets within Google Earth or other visualization programs, and understand what the data is telling them. Analyzing the data will allow learners to contemplate and make predictions on the impact associated with changing environmental conditions, within the context of a coastal setting. To Drill or Not To Drill is a multidisciplinary problem based module to increase students’ knowledge of problems associated with nonrenewable resource extraction. The controversial topic of drilling in the Arctic National Wildlife Refuge (ANWR) examines whether the economic benefit of the oil extracted from ANWR is worth the social cost of the environmental damage that such extraction may inflict. By attempting to answer this question, learners must balance the interests of preservation with the economic need for oil. The learners are exposed to the difficulties associated with a real world problem that requires trade-off between environmental trust and economic well-being. The Citizen Science module challenges students to translate scientific

  17. The C50T polymorphism of the cyclooxygenase-I gene and the risk of thrombotic events during low-dose therapy with acetyl salicylic acid

    NARCIS (Netherlands)

    Clappers, Nick; van Oijen, Martijn G. H.; Sundaresan, Santosh; Brouwer, Marc A.; te Morsche, Rene H. M.; Keuper, Wessel; Peters, Wilbert H. M.; Drenth, Joost P. H.; Verheugt, Freek W. A.

    2008-01-01

    prevents thrombotic events by inhibiting platelet cyclooxygenase-I (COX-1), thus reducing thromboxane A2 formation and platelet aggregation.The C50T polymorphism of COX-1 is associated with an impaired inhibition of both thromboxane production and in-vitro platelet aggregation by aspirin.We studied

  18. A substrate specificity-determining unit of three Lin12-Notch repeat modules is formed in trans within the pappalysin-1 dimer and requires a sequence stretch C-terminal to the third module

    DEFF Research Database (Denmark)

    Weyer, Kathrin; Boldt, Henning B; Poulsen, Christine B

    2007-01-01

    -A cleaves IGFBP-4 and IGFBP-5, whereas PAPP-A2 cleaves only IGFBP-5. The pappalysins contain three Lin12-Notch repeat (LNR1-3) modules, previously considered unique to the Notch receptor family in which they function to regulate receptor cleavage. In contrast to the Notch receptor where three LNR modules...

  19. Module-Amenability on Module Extension Banach Algebras

    Directory of Open Access Journals (Sweden)

    Davood Ebrahimi Bagha

    2014-05-01

    Full Text Available Let $A$ be a Banach algebra and $E$ be a Banach‎ ‎$A$-bimodule then $S=A\\oplus E$‎, ‎the $l^1$-direct sum of $A$ and $E$‎ ‎becomes a module extension Banach algebra when equipped with the‎ ‎algebras product $ (a‎ , ‎x‎. ‎(a'‎, ‎x' = (aa'‎ , ‎a.x'‎ + ‎x.a'$‎. ‎In this‎ ‎paper‎, ‎we investigate $\\triangle$-amenability for these Banach‎ ‎algebras and we show that for discrete inverse semigroup $S$ with‎ ‎the set of idempotents $E_{S}$‎, ‎the module extension Banach algebra $S=l^{1} (E_{S} \\op l^{1} (S$ is $ \\tr$-amenable‎ ‎as a $l^{1}(E_{S} $-module if and only if $l^{1}(E_{S}$ is amenable as Banach algebra‎.

  20. Allosteric interactions between agonists and antagonists within the adenosine A2A receptor-dopamine D2 receptor heterotetramer.

    Science.gov (United States)

    Bonaventura, Jordi; Navarro, Gemma; Casadó-Anguera, Verònica; Azdad, Karima; Rea, William; Moreno, Estefanía; Brugarolas, Marc; Mallol, Josefa; Canela, Enric I; Lluís, Carme; Cortés, Antoni; Volkow, Nora D; Schiffmann, Serge N; Ferré, Sergi; Casadó, Vicent

    2015-07-07

    Adenosine A2A receptor (A2AR)-dopamine D2 receptor (D2R) heteromers are key modulators of striatal neuronal function. It has been suggested that the psychostimulant effects of caffeine depend on its ability to block an allosteric modulation within the A2AR-D2R heteromer, by which adenosine decreases the affinity and intrinsic efficacy of dopamine at the D2R. We describe novel unsuspected allosteric mechanisms within the heteromer by which not only A2AR agonists, but also A2AR antagonists, decrease the affinity and intrinsic efficacy of D2R agonists and the affinity of D2R antagonists. Strikingly, these allosteric modulations disappear on agonist and antagonist coadministration. This can be explained by a model that considers A2AR-D2R heteromers as heterotetramers, constituted by A2AR and D2R homodimers, as demonstrated by experiments with bioluminescence resonance energy transfer and bimolecular fluorescence and bioluminescence complementation. As predicted by the model, high concentrations of A2AR antagonists behaved as A2AR agonists and decreased D2R function in the brain.

  1. Index modulation for 5G wireless communications

    CERN Document Server

    Wen, Miaowen; Yang, Liuqing

    2017-01-01

    This book presents a thorough examination of index modulation, an emerging 5G modulation technique. It includes representative transmitter and receiver design, optimization, and performance analysis of index modulation in various domains. First, the basic spatial modulation system for the spatial domain is introduced. Then, the development of a generalized pre-coding aided quadrature spatial modulation system as well as a virtual spatial modulation system are presented. For the space-time domain, a range of differential spatial modulation systems are examined, along with the pre-coding design. Both basic and enhanced index modulated OFDM systems for the frequency domain are discussed, focusing on the verification of their strong capabilities in inter-carrier interference mitigation. Finally, key open problems are highlighted and future research directions are considered. Designed for researchers and professionals, this book is essential for anyone working in communications networking, 5G, and system design. A...

  2. Mounting support for a photovoltaic module

    Science.gov (United States)

    Brandt, Gregory Michael; Barsun, Stephan K.; Coleman, Nathaniel T.; Zhou, Yin

    2013-03-26

    A mounting support for a photovoltaic module is described. The mounting support includes a foundation having an integrated wire-way ledge portion. A photovoltaic module support mechanism is coupled with the foundation.

  3. PV module mounting method and mounting assembly

    Science.gov (United States)

    Lenox, Carl J.S.; Johnson, Kurt M.

    2013-04-23

    A method for mounting PV modules to a deck includes selecting PV module layout pattern so that adjacent PV module edges are spaced apart. PV mounting and support assemblies are secured to the deck according to the layout pattern using fasteners extending into the deck. The PV modules are placed on the PV mounting and support assemblies. Retaining elements are located over and secured against the upper peripheral edge surfaces of the PV modules so to secure them to the deck with the peripheral edges of the PV modules spaced apart from the deck. In some examples a PV module mounting assembly, for use on a shingled deck, comprises flashing, a base mountable on the flashing, a deck-penetrating fastener engageable with the base and securable to the deck so to secure the flashing and the base to the shingled deck, and PV module mounting hardware securable to the base.

  4. Liquid crystal television spatial light modulators

    Science.gov (United States)

    Liu, Hua-Kuang; Chao, Tien-Hsin

    1989-01-01

    The spatial light modulation characteristics and capabilities of the liquid crystal television (LCTV) spatial light modulators (SLMs) are discussed. A comparison of Radio Shack, Epson, and Citizen LCTV SLMs is made.

  5. Photoacoustic investigation of QCL modulation techniques

    International Nuclear Information System (INIS)

    Germer, M; Wolff, M

    2010-01-01

    High detection sensitivity and spectral selectivity is important for gas analysers to identify the measured compound and to detect low concentrations. We investigated three different modulation methods - pulse gate modulation, pulse frequency modulation and chopper modulation - for a new pulsed quantum cascade laser based photoacoustic sensor. The spectral selectivity and the detection limit for the three modulation methods are compared by measuring nitric oxide absorption lines and different concentrations. The highest detection sensitivity of 70 ppb was achieved with pulse gate modulation but at the lowest spectral resolution. The highest spectral resolution was achieved with chopper modulation but at the lowest detection sensitivity. It is demonstrated that for the three modulation methods a compromise has to be made between selectivity and sensitivity for each measuring task.

  6. Laser frequency modulation with electron plasma

    Science.gov (United States)

    Burgess, T. J.; Latorre, V. R.

    1972-01-01

    When laser beam passes through electron plasma its frequency shifts by amount proportional to plasma density. This density varies with modulating signal resulting in corresponding modulation of laser beam frequency. Necessary apparatus is relatively inexpensive since crystals are not required.

  7. Last LEP superconducting module travels to surface

    CERN Multimedia

    Patrice Loïez

    2001-01-01

    The last superconducting module is raised from the Large Electron-Positron (LEP) collider tunnel, through the main shaft, to the surface. Superconducting modules were only used in the LEP-2 phase of the accelerator, from 1996 to 2000.

  8. Pulse shaping using a spatial light modulator

    CSIR Research Space (South Africa)

    Botha, N

    2009-07-01

    Full Text Available Femtosecond pulse shaping can be done by different kinds of pulse shapers, such as liquid crystal spatial light modulators (LC SLM), acousto optic modulators (AOM) and deformable and movable mirrors. A few applications where pulse shaping...

  9. Preparing last LEP superconducting module for removal

    CERN Multimedia

    Patrice Loïez

    2000-01-01

    The last superconducting module travels along the LEP tunnel towards one of the shafts where it will be lifted to the surface. Superconducting modules were only used in the LEP-2 phase of the accelerator, from 1996 to 2000.

  10. Multichip module technology for automotive application

    Science.gov (United States)

    Johnson, R. Wayne; Evans, John L.; Bosley, Larry

    1995-01-01

    Advancements in multichip module technology are creating design freedoms previously unavailable to design engineers. These advancements are opening new markets for laminate based multichip module products. In particular, material improvements in laminate printed wiring boards are allowing multichip module technology to meet more stringent environmental conditions. In addition, improvements in encapsulants and adhesives are enhancing the capabilities of multichip module technology to meet harsh environment. Furthermore, improvements in manufacturing techniques are providing the reliability improvements necessary for use in high quality electronic systems. These advances are making multichip module technology viable for high volume, harsh environment applications like under-the-hood automotive electronics. This paper will provide a brief review of multichip module technology, a discussion of specific research activities with Chrysler for use of multichip modules in automotive engine controllers and finally a discussion of prototype multichip modules fabricated and tested.

  11. Perturbation theory for plasmonic modulation and sensing

    KAUST Repository

    Raman, Aaswath; Fan, Shanhui

    2011-01-01

    related to plasma frequency modulation in such systems. Our approach provides new physical insight for the design of plasmonic devices for biochemical sensing and optical modulation and future active metamaterial applications. © 2011 American Physical

  12. Modulation Algorithms for Manipulating Nuclear Spin States

    OpenAIRE

    Liu, Boyang; Zhang, Ming; Dai, Hong-Yi

    2013-01-01

    We exploit the impact of exact frequency modulation on transition time of steering nuclear spin states from theoretical point of view. 1-stage and 2-stage Frequency-Amplitude-Phase modulation (FAPM) algorithms are proposed in contrast with 1-stage and 3-stage Amplitude-Phase modulation (APM) algorithms. The sufficient conditions are further present for transiting nuclear spin states within the specified time by these four modulation algorithms. It is demonstrated that transition time performa...

  13. Automatic modulation classification principles, algorithms and applications

    CERN Document Server

    Zhu, Zhechen

    2014-01-01

    Automatic Modulation Classification (AMC) has been a key technology in many military, security, and civilian telecommunication applications for decades. In military and security applications, modulation often serves as another level of encryption; in modern civilian applications, multiple modulation types can be employed by a signal transmitter to control the data rate and link reliability. This book offers comprehensive documentation of AMC models, algorithms and implementations for successful modulation recognition. It provides an invaluable theoretical and numerical comparison of AMC algo

  14. Polybinary modulation for bandwidth limited optical links

    DEFF Research Database (Denmark)

    Vegas Olmos, Juan José; Jurado-Navas, Antonio

    2015-01-01

    form of partial response modulation, employs simple codification and filtering at the transmitter to drastically increase the spectral efficiency. At the receiver side, poly binary modulation requires low complexity direct detection and very little digital signal processing. This talk will review...... the recent results on poly binary modulation, comprising both binary and multilevel signals as seed signals. The results will show how poly binary modulation effectively reduces the bandwidth requirements on optical links while providing high spectral efficiency....

  15. CLIC Quadrupole Module final report

    CERN Document Server

    Artoos, K; Mainaud-Durand, H

    2013-01-01

    Future Linear colliders will need particle beam sizes in the nanometre range. The beam also needs to be stable all along the beam line. The CLIC Main Beam Quadrupole (MBQ) module has been defined and studied. It is meant as a test stand for stabilisation and pre-alignment with a MB Quadrupole. The main topic that has been tackled concerns the Quadrupole magnet stabilisation to 1nm at 1Hz. This is needed to obtain the desired CLIC luminosity of 2.1034 cm-2m-1. The deliverable was demonstrated by procuring a MBQ and by stabilising a powered and cooled CLIC MBQ quadrupole. In addition, the stabilisation system has to be compatible with the pre-alignment procedures. Pre-alignment movement resolution has been demonstrated to 1m. The last step is the combined test of stability with a quadrupole on a CLIC Module with the pre-alignment.

  16. Wavelength modulation spectroscopy of semiconductors

    Energy Technology Data Exchange (ETDEWEB)

    Kohn, S.E.

    1977-10-01

    The use of modulation spectroscopy to study the electronic properties of solids has been very productive. The construction of a wide range Wavelength Modulation Spectrometer to study the optical properties of solids is described in detail. Extensions of the working range of the spectrometer into the vacuum ultraviolet are discussed. Measurements of the reflectivity and derivative reflectivity spectra of the lead chalcogenides, the chalcopyrite ZnGeP/sub 2/, the layer compounds GaSe and GaS and their alloys, the ferroelectric SbSI, layer compounds SnS/sub 2/ and SnSe/sub 2/, and HfS/sub 2/ were made. The results of these measurements are presented along with their interpretation in terms of band structure calculations.

  17. Cavity Voltage Phase Modulation MD

    CERN Document Server

    Mastoridis, Themistoklis; Molendijk, John; Timko, Helga; CERN. Geneva. ATS Department

    2016-01-01

    The LHC RF/LLRF system is currently configured for extremely stable RF voltage to minimize transient beam loading effects. The present scheme cannot be extended beyond nominal beam current since the demanded power would exceed the peak klystron power and lead to saturation. A new scheme has therefore been proposed: for beam currents above nominal (and possibly earlier), the cavity phase modulation by the beam will not be corrected (transient beam loading), but the strong RF feedback and One-Turn Delay feedback will still be active for loop and beam stability in physics. To achieve this, the voltage set point will be adapted for each bunch. The goal of this MD was to test a new algorithm that would adjust the voltage set point to achieve the cavity phase modulation that would minimize klystron forward power.

  18. Gas separation membrane module assembly

    Science.gov (United States)

    Wynn, Nicholas P [Palo Alto, CA; Fulton, Donald A [Fairfield, CA

    2009-03-31

    A gas-separation membrane module assembly and a gas-separation process using the assembly. The assembly includes a set of tubes, each containing gas-separation membranes, arranged within a housing. The housing contains a tube sheet that divides the space within the housing into two gas-tight spaces. A permeate collection system within the housing gathers permeate gas from the tubes for discharge from the housing.

  19. Pulse amplitude modulated chlorophyll fluorometer

    Science.gov (United States)

    Greenbaum, Elias; Wu, Jie

    2015-12-29

    Chlorophyll fluorometry may be used for detecting toxins in a sample because of changes in micro algae. A portable lab on a chip ("LOAC") based chlorophyll fluorometer may be used for toxin detection and environmental monitoring. In particular, the system may include a microfluidic pulse amplitude modulated ("PAM") chlorophyll fluorometer. The LOAC PAM chlorophyll fluorometer may analyze microalgae and cyanobacteria that grow naturally in source drinking water.

  20. The Decision Module Working Paper

    Science.gov (United States)

    1973-12-01

    and goal change has received very little attention In the litera- ture on the analysis of choice situations. It has generally been the case that the...Decision Making: Approach and Prototype" (197:0, done In context of the Mesarovlc - Pestel World Model Projet’ The Issues dealing with «-he cho ce...Nelson, Winder, and Schuette (1973) on evolutionary economic growth models. The discussion of the two components of the decision module that follows

  1. Intensity-modulated radiation therapy.

    Science.gov (United States)

    Goffman, Thomas E; Glatstein, Eli

    2002-07-01

    Intensity-modulated radiation therapy (IMRT) is an increasingly popular technical means of tightly focusing the radiation dose around a cancer. As with stereotactic radiotherapy, IMRT uses multiple fields and angles to converge on the target. The potential for total dose escalation and for escalation of daily fraction size to the gross cancer is exciting. The excitement, however, has greatly overshadowed a range of radiobiological and clinical concerns.

  2. Development of GREET Catalyst Module

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Zhichao [Argonne National Lab. (ANL), Argonne, IL (United States); Benavides, Pahola T. [Argonne National Lab. (ANL), Argonne, IL (United States); Dunn, Jennifer B. [Argonne National Lab. (ANL), Argonne, IL (United States); Cronauer, Donald C. [Argonne National Lab. (ANL), Argonne, IL (United States)

    2015-09-01

    In this report, we develop energy and material flows for the production of five different catalysts (tar reforming, alcohol synthesis, Zeolite Socony Mobil-5 [ZSM-5], Mo/Co/ γ-Al2O3, and Pt/ γ-Al2O3) and two chemicals (olivine, dimethyl ether of polyethylene glycol [DEPG]). These compounds and catalysts are now included in the Greenhouse Gases, Regulated Emissions and Energy Use in Transportation (GREET™) catalyst module.

  3. Applying Economics Using Interactive Learning Modules

    Science.gov (United States)

    Goma, Ophelia D.

    2010-01-01

    This article describes the use of web-based, interactive learning modules in the principles of economics course. The learning modules introduce students to important, historical economic events while providing real-world application of the economic theory presented in class. Each module is designed to supplement and complement the economic theory…

  4. Relative injectivity and CS-modules

    Directory of Open Access Journals (Sweden)

    Mahmoud Ahmed Kamal

    1994-01-01

    Full Text Available In this paper we show that a direct decomposition of modules M⊕N, with N homologically independent to the injective hull of M, is a CS-module if and only if N is injective relative to M and both of M and N are CS-modules. As an application, we prove that a direct sum of a non-singular semisimple module and a quasi-continuous module with zero socle is quasi-continuous. This result is known for quasi-injective modules. But when we confine ourselves to CS-modules we need no conditions on their socles. Then we investigate direct sums of CS-modules which are pairwise relatively inective. We show that every finite direct sum of such modules is a CS-module. This result is known for quasi-continuous modules. For the case of infinite direct sums, one has to add an extra condition. Finally, we briefly discuss modules in which every two direct summands are relatively inective.

  5. New Technologies for Managing Cotton Modules

    Science.gov (United States)

    The use of RFID transponders in the module tags on round modules formed by John Deere harvesters has opened up new possibilities for managing modules and harvest data. Tools are needed to help integrate this new technology and provide additional value to growers and ginners. A mobile application w...

  6. Charging a Capacitor with a Photovoltaic Module

    Science.gov (United States)

    Aguilar, Horacio Munguía; Maldonado, Rigoberto Franco; Navarro, Luis Barba

    2017-01-01

    Charging a capacitor with a photovoltaic module is an experiment which reveals a lot about the modules characteristics. It is customary to represent these characteristics with an equivalent circuit whose elements represent its physical parameters. The behavior of a photovoltaic module is very similar to that of a single cell but the electric…

  7. 47 CFR 101.141 - Microwave modulation.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Microwave modulation. 101.141 Section 101.141... SERVICES Technical Standards § 101.141 Microwave modulation. (a) Microwave transmitters employing digital modulation techniques and operating below 25.25 GHz (except for MVDDS stations in the 12,200-12,700 MHz band...

  8. Antimicrobial and modulation effects of selected Ghanaian ...

    African Journals Online (AJOL)

    The ethanol extracts of the three plants studied here are good modulators as they reduced the MIC of ciprofloxacin and ketoconazole by factors that are comparable to that of reserpine. However the exact compounds and their exact mechanism of modulation require further investigation. Keywords: Anti-infective, modulation, ...

  9. Medical Terminology: Prefixes. Health Occupations Education Module.

    Science.gov (United States)

    Temple Univ., Philadelphia, PA. Div. of Vocational Education.

    This module on medical terminology (prefixes) is one of 17 modules designed for individualized instruction in health occupations education programs at both the secondary and postsecondary levels. This module consists of an introduction to prefixes, a list of resources needed, and three learning experiences. Each learning experience contains an…

  10. Specification of the GummyModule Language

    NARCIS (Netherlands)

    Malakuti Khah Olun Abadi, Somayeh

    2012-01-01

    The GummyModule language is an extension to the Java language and is the successor of the EventReactor language The GummyModule language adopts the linguistic constructs of offered by EventReactor to define event types, events and to publish events. As for EventReactor, GummyModule facilitates

  11. Unified Technical Concepts. Module 8: Force Transformers.

    Science.gov (United States)

    Technical Education Research Center, Waco, TX.

    This concept module on force transformers is one of thirteen modules that provide a flexible, laboratory-based physics instructional package designed to meet the specialized needs of students in two-year, postsecondary technical schools. Each of the thirteen concept modules discusses a single physics concept and how it is applied to each energy…

  12. Strain absorbent modules for cavity filling

    Energy Technology Data Exchange (ETDEWEB)

    1981-04-01

    Strain absorbent modules made from weldmesh panels and helical steel binders can be used, together with timber packing, to support the roof and sides of cavities instead of softwood and hardwood nogs. A description of these modules and a series of load tests and underground trials carried out on the modules is given.

  13. Building CMS Pixel Barrel Detectur Modules

    CERN Document Server

    König, S; Horisberger, R.; Meier, B.; Rohe, T.; Streuli, S.; Weber, R.; Kastli, H.Chr.; Erdmann, W.

    2007-01-01

    For the barrel part of the CMS pixel tracker about 800 silicon pixel detector modules are required. The modules are bump bonded, assembled and tested at the Paul Scherrer Institute. This article describes the experience acquired during the assembly of the first ~200 modules.

  14. Armstrong practices in Lunar Module simulator

    Science.gov (United States)

    1969-01-01

    Neil A. Armstrong, Commander for the Apollo 11 Moon-landing mission, practices for the historic event in a Lunar Module simulator in the Flight Crew Training building at KSC. Accompanying Armstrong on the Moon flight will be Command Module Pilot Michael Collins and Lunar Module Pilot Edwin E. Aldrin Jr.

  15. Postdictive modulation of visual orientation.

    Directory of Open Access Journals (Sweden)

    Takahiro Kawabe

    Full Text Available The present study investigated how visual orientation is modulated by subsequent orientation inputs. Observers were presented a near-vertical Gabor patch as a target, followed by a left- or right-tilted second Gabor patch as a distracter in the spatial vicinity of the target. The task of the observers was to judge whether the target was right- or left-tilted (Experiment 1 or whether the target was vertical or not (Supplementary experiment. The judgment was biased toward the orientation of the distracter (the postdictive modulation of visual orientation. The judgment bias peaked when the target and distracter were temporally separated by 100 ms, indicating a specific temporal mechanism for this phenomenon. However, when the visibility of the distracter was reduced via backward masking, the judgment bias disappeared. On the other hand, the low-visibility distracter could still cause a simultaneous orientation contrast, indicating that the distracter orientation is still processed in the visual system (Experiment 2. Our results suggest that the postdictive modulation of visual orientation stems from spatiotemporal integration of visual orientation on the basis of a slow feature matching process.

  16. Postdictive modulation of visual orientation.

    Science.gov (United States)

    Kawabe, Takahiro

    2012-01-01

    The present study investigated how visual orientation is modulated by subsequent orientation inputs. Observers were presented a near-vertical Gabor patch as a target, followed by a left- or right-tilted second Gabor patch as a distracter in the spatial vicinity of the target. The task of the observers was to judge whether the target was right- or left-tilted (Experiment 1) or whether the target was vertical or not (Supplementary experiment). The judgment was biased toward the orientation of the distracter (the postdictive modulation of visual orientation). The judgment bias peaked when the target and distracter were temporally separated by 100 ms, indicating a specific temporal mechanism for this phenomenon. However, when the visibility of the distracter was reduced via backward masking, the judgment bias disappeared. On the other hand, the low-visibility distracter could still cause a simultaneous orientation contrast, indicating that the distracter orientation is still processed in the visual system (Experiment 2). Our results suggest that the postdictive modulation of visual orientation stems from spatiotemporal integration of visual orientation on the basis of a slow feature matching process.

  17. Cerebral cortex modulation of pain

    Institute of Scientific and Technical Information of China (English)

    Yu-feng XIE; Fu-quan HUO; Jing-shi TANG

    2009-01-01

    Pain is a complex experience encompassing sensory-discriminative, affective-motivational and cognitiv e-emotional com-ponents mediated by different mechanisms. Contrary to the traditional view that the cerebral cortex is not involved in pain perception, an extensive cortical network associated with pain processing has been revealed using multiple methods over the past decades. This network consistently includes, at least, the anterior cingulate cortex, the agranular insular cortex, the primary (SⅠ) and secondary somatosensory (SⅡ) cortices, the ventrolateral orbital cortex and the motor cortex. These corti-cal structures constitute the medial and lateral pain systems, the nucleus submedius-ventrolateral orbital cortex-periaque-ductal gray system and motor cortex system, respectively. Multiple neurotransmitters, including opioid, glutamate, GABA and dopamine, are involved in the modulation of pain by these cortical structures. In addition, glial cells may also be in-volved in cortical modulation of pain and serve as one target for pain management research. This review discusses recent studies of pain modulation by these cerebral cortical structures in animals and human.

  18. Sexual Orientation Modulates Endocrine Stress Reactivity

    Science.gov (United States)

    Juster, Robert-Paul; Hatzenbuehler, Mark L.; Mendrek, Adrianna; Pfaus, James G.; Smith, Nathan Grant; Johnson, Philip Jai; Lefebvre-Louis, Jean-Philippe; Raymond, Catherine; Marin, Marie-France; Sindi, Shireen; Lupien, Sonia J.; Pruessner, Jens C.

    2015-01-01

    BACKGROUND Biological sex differences and sociocultural gender diversity influence endocrine stress reactivity. Although numerous studies have shown that men typically activate stronger stress responses than women when exposed to laboratory-based psychosocial stressors, it is unclear whether sexual orientation further modulates stress reactivity. Given that lesbian, gay, and bisexual (LGB) individuals frequently report heightened distress secondary to stigma-related stressors, we investigated whether cortisol stress reactivity differs between LGB individuals and heterosexual individuals in response to a well-validated psychosocial stressor. METHODS The study population comprised 87 healthy adults (mean age, 25 years) who were grouped according to their biological sex and their gendered sexual orientation: lesbian/bisexual women (n = 20), heterosexual women (n = 21), gay/bisexual men (n = 26), and heterosexual men (n = 20). Investigators collected 10 salivary cortisol samples throughout a 2-hour afternoon visit involving exposure to the Trier Social Stress Test modified to maximize between-sex differences. RESULTS Relative to heterosexual women, lesbian/bisexual women showed higher cortisol stress reactivity 40 min after exposure to the stressor. In contrast, gay/bisexual men displayed lower overall cortisol concentrations throughout testing compared with heterosexual men. Main findings were significant while adjusting for sex hormones (estradiol-to-progesterone ratio in women and testosterone in men), age, self-esteem, and disclosure status (whether LGB participants had completed their “coming out”). CONCLUSIONS Our results provide novel evidence for gender-based modulation of cortisol stress reactivity based on sexual orientation that goes beyond well-established between-sex differences. This study raises several important avenues for future research related to the physiologic functioning of LGB populations and gender diversity more broadly. PMID:25444167

  19. Sexual orientation modulates endocrine stress reactivity.

    Science.gov (United States)

    Juster, Robert-Paul; Hatzenbuehler, Mark L; Mendrek, Adrianna; Pfaus, James G; Smith, Nathan Grant; Johnson, Philip Jai; Lefebvre-Louis, Jean-Philippe; Raymond, Catherine; Marin, Marie-France; Sindi, Shireen; Lupien, Sonia J; Pruessner, Jens C

    2015-04-01

    Biological sex differences and sociocultural gender diversity influence endocrine stress reactivity. Although numerous studies have shown that men typically activate stronger stress responses than women when exposed to laboratory-based psychosocial stressors, it is unclear whether sexual orientation further modulates stress reactivity. Given that lesbian, gay, and bisexual (LGB) individuals frequently report heightened distress secondary to stigma-related stressors, we investigated whether cortisol stress reactivity differs between LGB individuals and heterosexual individuals in response to a well-validated psychosocial stressor. The study population comprised 87 healthy adults (mean age, 25 years) who were grouped according to their biological sex and their gendered sexual orientation: lesbian/bisexual women (n = 20), heterosexual women (n = 21), gay/bisexual men (n = 26), and heterosexual men (n = 20). Investigators collected 10 salivary cortisol samples throughout a 2-hour afternoon visit involving exposure to the Trier Social Stress Test modified to maximize between-sex differences. Relative to heterosexual women, lesbian/bisexual women showed higher cortisol stress reactivity 40 min after exposure to the stressor. In contrast, gay/bisexual men displayed lower overall cortisol concentrations throughout testing compared with heterosexual men. Main findings were significant while adjusting for sex hormones (estradiol-to-progesterone ratio in women and testosterone in men), age, self-esteem, and disclosure status (whether LGB participants had completed their "coming out"). Our results provide novel evidence for gender-based modulation of cortisol stress reactivity based on sexual orientation that goes beyond well-established between-sex differences. This study raises several important avenues for future research related to the physiologic functioning of LGB populations and gender diversity more broadly. Copyright © 2015 Society of Biological Psychiatry. Published

  20. Auditory sensitivity to spectral modulation phase reversal as a function of modulation depth.

    Science.gov (United States)

    Buss, Emily; Grose, John

    2018-01-01

    The present study evaluated auditory sensitivity to spectral modulation by determining the modulation depth required to detect modulation phase reversal. This approach may be preferable to spectral modulation detection with a spectrally flat standard, since listeners appear unable to perform the task based on the detection of temporal modulation. While phase reversal thresholds are often evaluated by holding modulation depth constant and adjusting modulation rate, holding rate constant and adjusting modulation depth supports rate-specific assessment of modulation processing. Stimuli were pink noise samples, filtered into seven octave-wide bands (0.125-8 kHz) and spectrally modulated in dB. Experiment 1 measured performance as a function of modulation depth to determine appropriate units for adaptive threshold estimation. Experiment 2 compared thresholds in dB for modulation detection with a flat standard and modulation phase reversal; results supported the idea that temporal cues were available at high rates for the former but not the latter. Experiment 3 evaluated spectral modulation phase reversal thresholds for modulation that was restricted to either one or two neighboring bands. Flanking bands of unmodulated noise had a larger detrimental effect on one-band than two-band targets. Thresholds for high-rate modulation improved with increasing carrier frequency up to 2 kHz, whereas low-rate modulation appeared more consistent across frequency, particularly in the two-band condition. Experiment 4 measured spectral weights for spectral modulation phase reversal detection and found higher weights for bands in the spectral center of the stimulus than for the lowest (0.125 kHz) or highest (8 kHz) band. Experiment 5 compared performance for highly practiced and relatively naïve listeners, and found weak evidence of a larger practice effect at high than low spectral modulation rates. These results provide preliminary data for a task that may provide a better estimate of

  1. Cross-Modulation Interference with Lateralization of Mixed-Modulated Waveforms

    Science.gov (United States)

    Hsieh, I-Hui; Petrosyan, Agavni; Goncalves, Oscar F.; Hickok, Gregory; Saberi, Kourosh

    2010-01-01

    Purpose: This study investigated the ability to use spatial information in mixed-modulated (MM) sounds containing concurrent frequency-modulated (FM) and amplitude-modulated (AM) sounds by exploring patterns of interference when different modulation types originated from different loci as may occur in a multisource acoustic field. Method:…

  2. Nuclear Instrumentation Module (NIM) standard logic processor as a portal signal analyzer

    International Nuclear Information System (INIS)

    Minges, G.P.

    1978-01-01

    A general purpose electronic logic processor has been designed into a 2 wide NIM (Nuclear Instrumentation Module) bin module. The unit utilizes a microprocessor to achieve necessary versatility. The processor's first use is as a new generation signal analyzer for use in radiometric personnel and vehicle portal monitors. Significant improvements have been obtained in sensitivity and stability over existing analog discriminators. The new analyzer is presently being used to update personnel and vehicle portal monitoring systems

  3. "Chess-board pattern" spatial modulation of magnetization. Assessment of myocardial function

    DEFF Research Database (Denmark)

    Thomsen, C

    1992-01-01

    . Through spatial modulation of the magnetization the entire image can be labeled in different patterns. Two new pulse sequences are presented, giving a chess-board like spatial modulation. These pulse sequences have several advantages compared with the previously published methods, as the modulation time...... is half that required to obtain a 2-dimensional grid, the area in the image with high signal intensity was significantly larger, and the radiofrequency power deposition was substantially decreased. By labeling the heart at diastole the chess-board pattern tagging of the heart wall could be followed...

  4. Development of the module inspection system for new standardized radiation monitoring modules

    International Nuclear Information System (INIS)

    Furukawa, Masami; Shimizu, Kazuaki; Hiruta, Toshihito; Mizugaki, Toshio; Ohi, Yoshihiro; Chida, Tooru.

    1994-10-01

    This report mentions about the module inspection system which does the maintenance check of the monitoring modules adapted the new monitoring standard, as well as the result of the verification of the modules. The module inspection system is the automatic measurement system with the computer. The system can perform the functional and the characteristic examination of the monitoring modules, the calibration with radiation source and inspection report. In the verification of the monitoring module, three major items were tested, the adaptability for the new monitoring standard, the module functions and each characteristics. All items met the new monitoring standard. (author)

  5. Model Development of Degradation of PV Modules Backsheet with Locating Place of Module

    Energy Technology Data Exchange (ETDEWEB)

    Kempe, Michael D [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Wang, Yu [Case Western Reserve University; Fairbrother, Andrew [National Institute of Standards and Technology (NIST); Merzlic, Sebastien [Arkema; Julien, Scott [Northeastern University; Fridman, Lucas S. [Case Western Reserve University; Loyer, Camille [Arkema; Lefebvre, Amy L. [Arkema; O' Brien, Gregory [Arkema; Gu, Xiaohong [National Institute of Standards and Technology (NIST); Ji, Liang [Underwriters Laboratories; Boyce, Kenneth P. [Underwriters Laboratories; Wan, Kai-tak [Northeastern University; French, Roger H. [Case Western Reserve University; Bruckman, Laura S. [Case Western Reserve University

    2017-08-23

    Performance of a photovoltaic (PV) module is related to the micro-environment around the module. The position of photovoltaic modules in an array row have a large effect on the yellowing and gloss of PV module backsheet exposed in Dfa climatic zone (Gaithersburg, MD) with a polyethylene naphthalate (PEN) outer layer. Stress/Response models of yellowing and gloss-losing as function of location parameters of module, including the shed, row, measurement position in a same module and the distance of module location to the row center, are under development. The module installation height had the greatest influence on degradation of PEN PV backsheet in the Dfa climatic zone. The module backsheets at the end of an array have higher degradation rate (edge effect). The edge effect decreases with increasing of module installation heights.

  6. Annexin A2 in Proliferative Vitreoretinopathy

    Science.gov (United States)

    2017-10-01

    that breaches the blood-retinal barrier, leakage of plasma proteins and circulating blood cells, possibly together with local hypoxia, conspire to...immunofluorescence staining to document the migration of A2-positive cells from the RPE to the surface of the retina in PVR (Fig. 3). We have also detected a few...readily detected (Fig. 9B, 9C). Cells in both groups were also positive for A2. These data indicate that expression of A2 in both RPE cells and

  7. Can we trust module-respect heuristics?

    International Nuclear Information System (INIS)

    Mo, Yuchang

    2013-01-01

    BDD (Binary Decision Diagrams) have proven to be a very efficient tool to assess Fault Trees. However, the size of BDD, and therefore the efficiency of the whole methodology, depends dramatically on the choice of variable ordering. The determination of the best variable ordering is intractable. Therefore, heuristics have been designed to select reasonably good variable orderings. One very important common feature for good static heuristics is to respect modules. In this paper, the notion of module-respect is studied in a systematic way. It is proved that under certain condition there always exists an optimal ordering that respects modules. This condition is that for each module there is always a smallest module BDD and each included module variable appears only once. On the other hand, it is shown that for the trees not satisfying the above sufficient condition the optimal orderings may not be able to be directly generated using module-respect heuristics, even when the shuffling strategy is used.

  8. APOLLO 10 ASTRONAUT ENTERS LUNAR MODULE SIMULATOR

    Science.gov (United States)

    1969-01-01

    Apollo 10 lunar module pilot Eugene A. Cernan prepares to enter the lunar module simulator at the Flight Crew Training Building at the NASA Spaceport. Cernan, Apollo 10 commander Thomas P. Stafford and John W. Young, command module pilot, are to be launched May 18 on the Apollo 10 mission, a dress rehearsal for a lunar landing later this summer. Cernan and Stafford are to detach the lunar module and drop to within 10 miles of the moon's surface before rejoining Young in the command/service module. Looking on as Cernan puts on his soft helmet is Snoopy, the lovable cartoon mutt whose name will be the lunar module code name during the Apollo 10 flight. The command/service module is to bear the code name Charlie Brown.

  9. Automatic modulation recognition of communication signals

    CERN Document Server

    Azzouz, Elsayed Elsayed

    1996-01-01

    Automatic modulation recognition is a rapidly evolving area of signal analysis. In recent years, interest from the academic and military research institutes has focused around the research and development of modulation recognition algorithms. Any communication intelligence (COMINT) system comprises three main blocks: receiver front-end, modulation recogniser and output stage. Considerable work has been done in the area of receiver front-ends. The work at the output stage is concerned with information extraction, recording and exploitation and begins with signal demodulation, that requires accurate knowledge about the signal modulation type. There are, however, two main reasons for knowing the current modulation type of a signal; to preserve the signal information content and to decide upon the suitable counter action, such as jamming. Automatic Modulation Recognition of Communications Signals describes in depth this modulation recognition process. Drawing on several years of research, the authors provide a cr...

  10. Flexible packaging for PV modules

    Science.gov (United States)

    Dhere, Neelkanth G.

    2008-08-01

    Economic, flexible packages that provide needed level of protection to organic and some other PV cells over >25-years have not yet been developed. However, flexible packaging is essential in niche large-scale applications. Typical configuration used in flexible photovoltaic (PV) module packaging is transparent frontsheet/encapsulant/PV cells/flexible substrate. Besides flexibility of various components, the solder bonds should also be flexible and resistant to fatigue due to cyclic loading. Flexible front sheets should provide optical transparency, mechanical protection, scratch resistance, dielectric isolation, water resistance, UV stability and adhesion to encapsulant. Examples are Tefzel, Tedlar and Silicone. Dirt can get embedded in soft layers such as silicone and obscure light. Water vapor transmittance rate (WVTR) of polymer films used in the food packaging industry as moisture barriers are ~0.05 g/(m2.day) under ambient conditions. In comparison, light emitting diodes employ packaging components that have WVTR of ~10-6 g/(m2.day). WVTR of polymer sheets can be improved by coating them with dense inorganic/organic multilayers. Ethylene vinyl acetate, an amorphous copolymer used predominantly by the PV industry has very high O2 and H2O diffusivity. Quaternary carbon chains (such as acetate) in a polymer lead to cleavage and loss of adhesional strength at relatively low exposures. Reactivity of PV module components increases in presence of O2 and H2O. Adhesional strength degrades due to the breakdown of structure of polymer by reactive, free radicals formed by high-energy radiation. Free radical formation in polymers is reduced when the aromatic rings are attached at regular intervals. This paper will review flexible packaging for PV modules.

  11. Head position modulates optokinetic nystagmus.

    Science.gov (United States)

    Pettorossi, V E; Ferraresi, A; Botti, F M; Panichi, R; Barmack, N H

    2011-08-01

    Orientation and movement relies on both visual and vestibular information mapped in separate coordinate systems. Here, we examine how coordinate systems interact to guide eye movements of rabbits. We exposed rabbits to continuous horizontal optokinetic stimulation (HOKS) at 5°/s to evoke horizontal eye movements, while they were statically or dynamically roll-tilted about the longitudinal axis. During monocular or binocular HOKS, when the rabbit was roll-tilted 30° onto the side of the eye stimulated in the posterior → anterior (P → A) direction, slow phase eye velocity (SPEV) increased by 3.5-5°/s. When the rabbit was roll-tilted 30° onto the side of the eye stimulated in the A → P direction, SPEV decreased to ~2.5°/s. We also tested the effect of roll-tilt after prolonged optokinetic stimulation had induced a negative optokinetic afternystagmus (OKAN II). In this condition, the SPEV occurred in the dark, "open loop." Modulation of SPEV of OKAN II depended on the direction of the nystagmus and was consistent with that observed during "closed loop" HOKS. Dynamic roll-tilt influenced SPEV evoked by HOKS in a similar way. The amplitude and the phase of SPEV depended on the frequency of vestibular oscillation and on HOKS velocity. We conclude that the change in the linear acceleration of the gravity vector with respect to the head during roll-tilt modulates the gain of SPEV depending on its direction. This modulation improves gaze stability at different image retinal slip velocities caused by head roll-tilt during centric or eccentric head movement.

  12. Amplitude modulation reflectometer for FTU

    International Nuclear Information System (INIS)

    Zerbini, M.; Buratti, P.; Centioli, C.; Amadeo, P.

    1995-06-01

    Amplitude modulation (AM) reflectometry is a modification of the classical frequency sweep technique which allows to perform unambiguous phase delay measurements. An eight-channel AM reflectometer has been realized for the measurement of density profiles on the FTU tokamak in the range. The characteristics of the instrument have been determined in extensive laboratory tests; particular attention has been devoted to the effect of interference with parasitic reflections. The reflectometer is now operating on FTU. Some examples of the first experimental data are discussed

  13. Klystrons and modulators for SBLC

    Energy Technology Data Exchange (ETDEWEB)

    Bieler, M.; Choroba, S.; Hameister, J.; Lewin, H.-Ch. [Deutsches Elektronen-Synchrotron DESY, Hamburg (Germany)

    1997-04-01

    For SBLC, the DESY/THD S-band linear collider study, klystrons with 150 MW rf-pulse power at 50 Hz repetition rate and 3 {mu}s pulse duration are required [1]. This paper will give a short overview of the SBLC parameters and the S-band test linac at DESY. Two different modulator schemes, the conventional line type pulser and the hard tube pulser, will be discussed. After a brief description of the 150 MW S-band klystron the first operating experience with the klystron and a line type pulser at DESY will be presented. (author)

  14. Projective modules and complete intersections

    CERN Document Server

    Mandal, Satya

    1997-01-01

    In these notes on "Projective Modules and Complete Intersections" an account on the recent developments in research on this subject is presented. The author's preference for the technique of Patching isotopic isomorphisms due to Quillen, formalized by Plumsted, over the techniques of elementary matrices is evident here. The treatment of Basic Element theory here incorporates Plumstead's idea of the "generalized dimension functions". These notes are highly selfcontained and should be accessible to any graduate student in commutative algebra or algebraic geometry. They include fully self-contained presentations of the theorems of Ferrand-Szpiro, Cowsik-Nori and the techniques of Lindel.

  15. WEBSITE EXECUTION OF CAD MODULES

    Directory of Open Access Journals (Sweden)

    A. A. Lyalinsky

    2013-01-01

    Full Text Available Web-based interface of modules that are part of the computer-aided design system in microelectronics is considered. The influence of several factors (available computer  memory, maximum allowed run time, degree of homogeneity of the software on the structure of the created system is investigated. Synchronous and asynchronous variants of interaction between control and executive parts are described. References on the systems that allow an access to applications in CAD microelectronics and are based on the principles discussed in this article are given.

  16. Temperature Modulated Nanomechanical Thermal Analysis

    DEFF Research Database (Denmark)

    Alves, Gustavo Marcati A.; Bose-Goswami, Sanjukta; Mansano, Ronaldo D.

    2018-01-01

    The response of microcantilever deflection to complex heating profiles was used to study thermal events like glass transition and enthalpy relaxation on nanograms of the biopolymer Poly(lactic-co-glycolic acid) (PLGA). The use of two heating rates enables the separation of effects on the deflection...... response that depends on previous thermal history (non-reversing signal) and effects that depends only on the heating rate variation (reversing signal). As these effects may appear superposed in the total response, temperature modulation can increase the measurement sensitivity to some thermal events when...

  17. Modulation of Current Source Inverter

    Directory of Open Access Journals (Sweden)

    Golam Reza Arab Markadeh

    2011-04-01

    Full Text Available Direct torque control with Current Source Inverter (CSI instead of voltage source inverter is so appropriate because of determining the torque of induction motor with machine current and air gap flux. In addition, Space-Vector Modulation (SVM is a more proper method for CSI because of low order harmonics reduction, lower switching frequency and easier implementation. This paper introduces the SVM method for CSI and uses the proposed inverter for vector control of an induction motor. The simulation results illustrate fast dynamic response and desirable torque and speed output. Fast and accurate response to changes of speed and load torque reference completely proves the prominence of this method.

  18. Epigenetic modulators of thyroid cancer.

    Science.gov (United States)

    Rodríguez-Rodero, Sandra; Delgado-Álvarez, Elías; Díaz-Naya, Lucía; Martín Nieto, Alicia; Menéndez Torre, Edelmiro

    2017-01-01

    There are some well known factors involved in the etiology of thyroid cancer, including iodine deficiency, radiation exposure at early ages, or some genetic changes. However, epigenetic modulators that may contribute to development of these tumors and be helpful to for both their diagnosis and treatment have recently been discovered. The currently known changes in DNA methylation, histone modifications, and non-coding RNAs in each type of thyroid carcinoma are reviewed here. Copyright © 2016 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. High-order modulation on a single discrete eigenvalue for optical communications based on nonlinear Fourier transform.

    Science.gov (United States)

    Gui, Tao; Lu, Chao; Lau, Alan Pak Tao; Wai, P K A

    2017-08-21

    In this paper, we experimentally investigate high-order modulation over a single discrete eigenvalue under the nonlinear Fourier transform (NFT) framework and exploit all degrees of freedom for encoding information. For a fixed eigenvalue, we compare different 4 bit/symbol modulation formats on the spectral amplitude and show that a 2-ring 16-APSK constellation achieves optimal performance. We then study joint spectral phase, spectral magnitude and eigenvalue modulation and found that while modulation on the real part of the eigenvalue induces pulse timing drift and leads to neighboring pulse interactions and nonlinear inter-symbol interference (ISI), it is more bandwidth efficient than modulation on the imaginary part of the eigenvalue in practical settings. We propose a spectral amplitude scaling method to mitigate such nonlinear ISI and demonstrate a record 4 GBaud 16-APSK on the spectral amplitude plus 2-bit eigenvalue modulation (total 6 bit/symbol at 24 Gb/s) transmission over 1000 km.

  20. Preliminary modulation transfer function study on amorphous silicon

    International Nuclear Information System (INIS)

    Khairul Anuar Mohd Salleh; Ab Razak Hamzah; Mohd Ashhar Khalid

    2006-01-01

    Modulation Transfer Function, (MTF) is the scientific means of evaluating the fundamental spatial resolution performance of an imaging system. In the study, the modulation transfer function of an amorphous silicon (aSi) sensor array is measured by using Edge Spread Function (ESF) Technique which is extracting a profile from the linearised image of the sharp edge. The Platinum foil is used to determine the ESF. The detector under study was a 2,304 (h) x 3,200 (v) total pixel matrix, 127 μm2 pixel pitch, 57% fill factor and using Gd2O2S:Tb Kodak Lanex Regular as the conversion screen. The ESF measurement is done by using 75 - 100 kV range of x-ray with constant mA. (Author)

  1. Bag-like contaminant control work module

    International Nuclear Information System (INIS)

    Buchanan, H.; Jacobson, E.B.

    1982-01-01

    A bag-like contaminant control work module is formed from a flexible impervious membrane which is inflated inside of an enclosed workspace to protect workers in the module from contaminants. The workspace, such as in a nuclear power steam generator, has a portal or manway opening into the workspace into which the module is secured by a module passageway. The module includes one or more glove boxes, in which the workers perform their assigned tasks after passing through the passageway and portal. The module includes one or more absolute filters allowing passage of air flow through the module passageway and into the workspace only through the filters. The module may include an auxiliary passageway secured to the outside of the module passageway and also secured in the portal opening and through which items can be passed back and forth to the worker in the glove box from outside the portal. The module is invertible so that it can be pulled out of the workspace trapping all the contaminants therein and disposed of without handling the contaminants

  2. Nutritional Modulation of Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Martin O. Weickert

    2012-01-01

    Full Text Available Insulin resistance has been proposed as the strongest single predictor for the development of Type 2 Diabetes (T2DM. Chronic oversupply of energy from food, together with inadequate physical activity, have been recognized as the most relevant factors leading to overweight, abdominal adiposity, insulin resistance, and finally T2DM. Conversely, energy reduced diets almost invariably to facilitate weight loss and reduce abdominal fat mass and insulin resistance. However, sustained weight loss is generally difficult to achieve, and distinct metabolic characteristics in patients with T2DM further compromise success. Therefore, investigating the effects of modulating the macronutrient composition of isoenergetic diets is an interesting concept that may lead to additional important insights. Metabolic effects of various different dietary concepts and strategies have been claimed, but results from randomized controlled studies and particularly from longer-term-controlled interventions in humans are often lacking. However, some of these concepts are supported by recent research, at least in animal models and short-term studies in humans. This paper provides an update of the current literature regarding the role of nutrition in the modulation of insulin resistance, which includes the discussion of weight-loss-independent metabolic effects of commonly used dietary concepts.

  3. Serial powering of pixel modules

    International Nuclear Information System (INIS)

    Stockmanns, Tobias; Fischer, Peter; Huegging, Fabian; Peric, Ivan; Runolfsson, O.; Wermes, Norbert

    2003-01-01

    Modern pixel detectors for the next generation of high-energy collider experiments like LHC use readout electronics in deep sub-micron technology. Chips in this technology need a low supply voltage of 2-2.5 V alongside high current consumption to achieve the desired performance. The high supply current leads to significant voltage drops in the long and low mass supply cables so that voltage fluctuations at the chips are induced, when the supply current changes. This problem scales with the number of modules when connected in parallel to the power supplies. An alternative powering scheme connects several modules in series resulting in a higher supply voltage but a lower current consumption of the chain and therefore a much lower voltage drop in the cables. In addition the amount of cables needed to supply the detector is vastly reduced. The concept and features of serial powering are presented and studies of the implementation of this technology as an alternative for the ATLAS pixel detector are shown. In particular, it is shown that the potential risk of powering in series can be addressed and eliminated

  4. Bioelectric modulation of macrophage polarization

    Science.gov (United States)

    Li, Chunmei; Levin, Michael; Kaplan, David L.

    2016-02-01

    Macrophages play a critical role in regulating wound healing and tissue regeneration by changing their polarization state in response to local microenvironmental stimuli. The native roles of polarized macrophages encompass biomaterials and tissue remodeling needs, yet harnessing or directing the polarization response has been largely absent as a potential strategy to exploit in regenerative medicine to date. Recent data have revealed that specific alteration of cells’ resting potential (Vmem) is a powerful tool to direct proliferation and differentiation in a number of complex tissues, such as limb regeneration, craniofacial patterning and tumorigenesis. In this study, we explored the bioelectric modulation of macrophage polarization by targeting ATP sensitive potassium channels (KATP). Glibenclamide (KATP blocker) and pinacidil (KATP opener) treatment not only affect macrophage polarization, but also influence the phenotype of prepolarized macrophages. Furthermore, modulation of cell membrane electrical properties can fine-tune macrophage plasticity. Glibenclamide decreased the secretion and gene expression of selected M1 markers, while pinacidil augmented M1 markers. More interestingly, glibencalmide promoted macrophage alternative activation by enhancing certain M2 markers during M2 polarization. These findings suggest that control of bioelectric properties of macrophages could offer a promising approach to regulate macrophage phenotype as a useful tool in regenerative medicine.

  5. Attentional modulation of reflex cough.

    Science.gov (United States)

    Janssens, Thomas; Silva, Mitchell; Davenport, Paul W; Van Diest, Ilse; Dupont, Lieven J; Van den Bergh, Omer

    2014-07-01

    Reflex cough is a defensive response generated in the brainstem in response to chemical and mechanical stimulation of the airways. However, converging evidence shows that reflex cough is also influenced by central neural control processes. In this study, we investigate whether reflex cough can be modulated by attentional focus on either external stimuli or internal cough-related stimuli. Healthy volunteers (N = 24; seven men; age range, 18-25 years) completed four blocks of citric acid-induced cough challenges while, simultaneously, auditory stimuli were presented. Within each block, four concentrations were administered (30, 100, 300 and 1,000 mM, randomized). During two subsequent blocks, participants focused their attention externally (counting tones). During the other two blocks, participants focused their attention internally (counting coughs). The order of attentional focus was counterbalanced across participants. Ratings of the urge to cough were collected after each challenge. Cough frequency was determined by audio recording. Cough frequency was higher when participants focused their attention internally vs externally (P Reflex cough can be modulated by attentional focus. Internally focused attention may be a mechanism involved in excessive (idiopathic) cough, while an external focus may be introduced as part of treatments targeting excessive cough.

  6. Serial powering of pixel modules

    CERN Document Server

    Stockmanns, Tobias; Hügging, Fabian Georg; Peric, I; Runólfsson, O; Wermes, Norbert

    2003-01-01

    Modern pixel detectors for the next generation of high-energy collider experiments like LHC use readout electronics in deep sub- micron technology. Chips in this technology need a low supply voltage of 2-2.5 V alongside high current consumption to achieve the desired performance. The high supply current leads to significant voltage drops in the long and low mass supply cables so that voltage fluctuations at the chips are induced, when the supply current changes. This problem scales with the number of modules when connected in parallel to the power supplies. An alternative powering scheme connects several modules in series resulting in a higher supply voltage but a lower current consumption of the chain and therefore a much lower voltage drop in the cables. In addition the amount of cables needed to supply the detector is vastly reduced. The concept and features of serial powering are presented and studies of the implementation of this technology as an alternative for the ATLAS pixel detector are shown. In par...

  7. KNN BASED CLASSIFICATION OF DIGITAL MODULATED SIGNALS

    Directory of Open Access Journals (Sweden)

    Sajjad Ahmed Ghauri

    2016-11-01

    Full Text Available Demodulation process without the knowledge of modulation scheme requires Automatic Modulation Classification (AMC. When receiver has limited information about received signal then AMC become essential process. AMC finds important place in the field many civil and military fields such as modern electronic warfare, interfering source recognition, frequency management, link adaptation etc. In this paper we explore the use of K-nearest neighbor (KNN for modulation classification with different distance measurement methods. Five modulation schemes are used for classification purpose which is Binary Phase Shift Keying (BPSK, Quadrature Phase Shift Keying (QPSK, Quadrature Amplitude Modulation (QAM, 16-QAM and 64-QAM. Higher order cummulants (HOC are used as an input feature set to the classifier. Simulation results shows that proposed classification method provides better results for the considered modulation formats.

  8. Self oscillating PWM modulators, a topological comparison

    DEFF Research Database (Denmark)

    Poulsen, Søren; Andersen, Michael Andreas E.

    2004-01-01

    or fs/ð range respectively, where fs is the switching frequency of the converter. For some applications this will require unacceptable high switching frequency to achieve enough control loop bandwidth for the desired dynamic performance. With self oscillating modulators, the open loop bandwidth is equal...... to fs which makes this type of modulators an excellent choice for a wide range of applications. Self oscillating PWM modulators can be made in a number of ways, either as voltage or current mode modulators, and the self oscillating behavior can be achieved either by using hysteresis control...... or by shaping the open loop function of the modulator so its gain and phase response causes a closed loop natural oscillation. The two main types of self oscillating modulators have many similarities, but differences in dynamic performance and linearity are present. The work presented is related to the author...

  9. Power module assemblies with staggered coolant channels

    Science.gov (United States)

    Herron, Nicholas Hayden; Mann, Brooks S; Korich, Mark D

    2013-07-16

    A manifold is provided for supporting a power module assembly with a plurality of power modules. The manifold includes a first manifold section. The first face of the first manifold section is configured to receive the first power module, and the second face of the first manifold section defines a first cavity with a first baseplate thermally coupled to the first power module. The first face of the second manifold section is configured to receive the second power module, and the second face of the second manifold section defines a second cavity with a second baseplate thermally coupled to the second power module. The second face of the first manifold section and the second face of the second manifold section are coupled together such that the first cavity and the second cavity form a coolant channel. The first cavity is at least partially staggered with respect to second cavity.

  10. SUPPORT CARD FOR THE FORWARD SCT MODULE

    CERN Document Server

    Greenall, A

    2002-01-01

    Previously in the development and testing stage of ATLAS SCT Forward modules support cards have been used which interface the module to the DAQ by using only the Redundant inputs for the module configuration and the 'spying' of the ABCD Master chip(s) data. As module development has matured there is now a necessity to be able to test modules in the laboratory using also their Primary input/output data routes i.e. using the optical chips DORIC [1] and VDC [2] but without the need of optical fibres. A Forward Kapton Support Card, FKSC, has been developed so that both Primary and Redundant data routes can be used for module testing.

  11. Induction accelerator test module for HIF

    International Nuclear Information System (INIS)

    Faltens, A.

    1991-04-01

    An induction linac test module suitable for investigating the drive requirements and the longitudinal coupling impedance of a high-power ion induction linac has been constructed by the Heavy Ion Fusion (HIF) group at LBL. The induction linac heavy ion driver for inertial confinement fusion (ICF) as presently envisioned uses multiple parallel beams which are transported in separate focusing channels but accelerated together in the induction modules. The resulting induction modules consequently have large beam apertures-1--2 meters in diameter- and correspondingly large outside diameters. The module geometry is related to a low-frequency ''gap capacity'' and high-frequency structural resonances, which are affected by the magnetic core loading and the module pulser impedance. A description of the test module and preliminary results are presented. 3 figs

  12. Bactericidal effectiveness of modulated UV light

    International Nuclear Information System (INIS)

    Bank, H.L.; John, J.; Schmehl, M.K.; Dratch, R.J.

    1990-01-01

    Studies were designed to evaluate the effectiveness of pulsed modulated UV light waveforms for killing bacteria. Exposure of five strains of bacteria to the modulated information encoded in the light decreased the colony population from a confluent lawn to less than 20 colonies. However, approximately 2,000 colonies survived treatment with the same intensity and time of exposure to UV light lacking the modulated information

  13. Fast heat flux modulation at the nanoscale

    OpenAIRE

    van Zwol, P. J.; Joulain, K.; Abdallah, P. Ben; Greffet, J. J.; Chevrier, J.

    2011-01-01

    We introduce a new concept for electrically controlled heat flux modulation. A flux contrast larger than 10 dB is expected with switching time on the order of tens of nanoseconds. Heat flux modulation is based on the interplay between radiative heat transfer at the nanoscale and phase change materials. Such large contrasts are not obtainable in solids, or in far field. As such this opens up new horizons for temperature modulation and actuation at the nanoscale.

  14. String Stretching, Frequency Modulation, and Banjo Clang

    OpenAIRE

    Politzer, David

    2014-01-01

    The banjo’s floating bridge, string break angle, and flexible drumhead all contribute to substantial audio range frequency modulation. From the world of electronic music synthesis, it is known that modulating higher frequency sounds with lower acoustic frequencies leads to metallic and bell-like tone. The mechanics of the banjo does just that quite naturally, modulating fundamentals and harmonics with the motion of the bridge. In technical terms, with a floating bridge, string stretching is f...

  15. Computing optimal interfacial structure of modulated phases

    OpenAIRE

    Xu, Jie; Wang, Chu; Shi, An-Chang; Zhang, Pingwen

    2016-01-01

    We propose a general framework of computing interfacial structures between two modulated phases. Specifically we propose to use a computational box consisting of two half spaces, each occupied by a modulated phase with given position and orientation. The boundary conditions and basis functions are chosen to be commensurate with the bulk structures. It is observed that the ordered nature of modulated structures stabilizes the interface, which enables us to obtain optimal interfacial structures...

  16. Generalized module extension Banach algebras: Derivations and ...

    African Journals Online (AJOL)

    Let A and X be Banach algebras and let X be an algebraic Banach A-module. Then the ℓ-1direct sum A x X equipped with the multiplication (a; x)(b; y) = (ab; ay + xb + xy) (a; b ∈ A; x; y ∈ X) is a Banach algebra, denoted by A ⋈ X, which will be called "a generalized module extension Banach algebra". Module extension ...

  17. Production chain of CMS pixel modules

    CERN Multimedia

    2006-01-01

    The pictures show the production chain of pixel modules for the CMS detector. Fig.1: overview of the assembly procedure. Fig.2: bump bonding with ReadOut Chip (ROC) connected to the sensor. Fig.3: glueing a raw module onto the baseplate strips. Fig.4: glueing of the High Density Interconnect (HDI) onto a raw module. Fig.5: pull test after heat reflow. Fig.6: wafer sensor processing, Indium evaporation.

  18. 7 CFR 15a.2 - Definitions.

    Science.gov (United States)

    2010-01-01

    ... FINANCIAL ASSISTANCE Introduction § 15a.2 Definitions. As used in this part, the term: (a) Title IX means... political subdivision thereof, of any instrumentality of a State or political subdivision thereof, any...) Offers academic study beyond the bachelor of arts or bachelor of science degree, whether or not leading...

  19. 42 CFR 51a.2 - Definitions.

    Science.gov (United States)

    2010-10-01

    ... CHILD HEALTH § 51a.2 Definitions. Act means the Social Security Act, as amended. Genetic diseases means... accredited school of medicine and a full-time academic medical staff holding faculty status in such school of medicine. Secretary means the Secretary of Health and Human Services or his or her designee. ...

  20. Zingiber officinale Roscoe aqueous extract modulates ...

    African Journals Online (AJOL)

    Zingiber officinale Roscoe aqueous extract modulates Matrixmetalloproteinases and tissue inhibitors of Metalloproteinases expressions in Dengue virus-infected cells: implications for prevention of vascular permeability.

  1. ATLAS SCT - Progress on the Silicon Modules

    CERN Multimedia

    Tyndel, M.

    The ATLAS SCT consists of 4088 silicon modules. Each module is made up of 4 silicon sensors with 1536 readout strips. Individual strips are connected to FE amplifiers, discriminators and pipelines on the module, i.e. there are 12 radiation hard ASICs, each containing 128 channels on the module. The sensors and the ASICs were developed for the ATLAS experiment and production is proceeding smoothly with over half the components delivered. The components of a module - 4 silicon sensors, a Cu/polyimide hybrid and pitch adaptor, and 12 ASICs - need to be carefully and precisely assembled onto a carbon and ceramic framework, which supports the module and removes the heat. Eleven production clusters are preparing to carry this out over the next two years. An important milestone for the barrel modules has been passed with the first cluster (KEK) now in production (~40 modules produced). A second cluster UK-B has qualified by producing five modules within specification (see below) and is about to start production. T...

  2. Frequency-Diversity Reception for Phase Modulation

    Science.gov (United States)

    Brockman, M. H.

    1984-01-01

    Signal-to-noise ratio improved. System receives phase modulation transmitted simultaneously on different carrier frequencies. Used for carriers received through different antennas or through same antenna.

  3. PLC control of 50 MW klystron modulators

    International Nuclear Information System (INIS)

    Shang Lei; Liu Gongfa; Chen Liping; Lu Yeming; Hong Jun; Zhang Yi; Zhao Feng

    2004-01-01

    Upgrade project of the 50 MW klystron modulators of Hefei Light Source (HLS) was firstly introduced. PLC control system of modulators was employed to replace the old control and monitor system, which was based on relay logic circuit and manual operation method. the PLC system becomes a sub system of the new EPICS control system of HLS. Constant-current, switch-mode and high voltage power supplies were adopted to replace the old 50 Hz power supplies. The technology of modulators was improved and operation was more reliable. The design method, hardware and software of PLC control of modulators were described and the performance was presented. (authors)

  4. NLC Hybrid Solid State Induction Modulator

    CERN Document Server

    Cassel, R L; Pappas, G C; Delamare, J E

    2004-01-01

    The Next Linear Collider accelerator proposal at SLAC requires a high efficiency, highly reliable, and low cost pulsed power modulator to drive the X-band klystrons. The original NLC envisions a solid state induction modulator design to drive up to 8 klystrons to 500 kV for 3 μs at 120 PPS with one modulator delivering greater than 1,000 MW pulse, at 500 kW average. A change in RF compression techniques resulted in only two klystrons needed pulsing per modulator at a reduced pulse width of 1.6 μsec or approximately 250 MW of the pulsed power and 80 kW of average powers. A prototype Design for Manufacturability (DFM) 8-pack modulator was under construction at the time of the change, so a redirection of modulator design was in order. To utilities the equipment which had already be fabricated, a hybrid modulator was designed and constructed using the DFM induction modulator parts and a conventional pulse transformer. The construction and performance of this hybrid two klystron Induction modul...

  5. Modulation of gene expression made easy

    DEFF Research Database (Denmark)

    Solem, Christian; Jensen, Peter Ruhdal

    2002-01-01

    A new approach for modulating gene expression, based on randomization of promoter (spacer) sequences, was developed. The method was applied to chromosomal genes in Lactococcus lactis and shown to generate libraries of clones with broad ranges of expression levels of target genes. In one example...... that the method can be applied to modulating the expression of native genes on the chromosome. We constructed a series of strains in which the expression of the las operon, containing the genes pfk, pyk, and ldh, was modulated by integrating a truncated copy of the pfk gene. Importantly, the modulation affected...

  6. Millimeter Wave Modulators Using Quantum Dots

    National Research Council Canada - National Science Library

    Prather, Dennis W

    2008-01-01

    In this effort electro-optic modulators for millimeter wave sensing and imaging were developed and demonstrated via design, fabrication, and experimental characterization of multi layer quantum dot...

  7. SLAC modulator system improvements and reliability results

    International Nuclear Information System (INIS)

    Donaldson, A.R.

    1998-06-01

    In 1995, an improvement project was completed on the 244 klystron modulators in the linear accelerator. The modulator system has been previously described. This article offers project details and their resulting effect on modulator and component reliability. Prior to the project, the authors had collected four operating cycles (1991 through 1995) of MTTF data. In this discussion, the '91 data will be excluded since the modulators operated at 60 Hz. The five periods following the '91 run were reviewed due to the common repetition rate at 120 Hz

  8. Global model structures for ∗-modules

    DEFF Research Database (Denmark)

    Böhme, Benjamin

    2018-01-01

    We extend Schwede's work on the unstable global homotopy theory of orthogonal spaces and L-spaces to the category of ∗-modules (i.e., unstable S-modules). We prove a theorem which transports model structures and their properties from L-spaces to ∗-modules and show that the resulting global model...... structure for ∗-modules is monoidally Quillen equivalent to that of orthogonal spaces. As a consequence, there are induced Quillen equivalences between the associated model categories of monoids, which identify equivalent models for the global homotopy theory of A∞-spaces....

  9. METHOD AND MODULE FOR OPTICAL SUBCARRIER LABELLING

    DEFF Research Database (Denmark)

    2004-01-01

    The present invention relates to optical labelling in WDM networks, in that it provides a method and a module to be used in subcarrier label generation and switching in network edge nodes and core switch nodes. The methods and modules are typically employed in Optical Subcarrier Multiplexing (OSCM......) transmitters. The payload and the label are encoded independently on optical carrier and subcarrier signals respectively, using electro-optical modulators. The invention applies single or double sideband carrier-suppressed modulation to generate subcarrier signals for encoding of the label. Thereby the payload...... encoded carrier signal and the label encoded subcarrier signal can be coupled directly without prior filtering....

  10. Photovoltaic module energy rating methodology development

    Energy Technology Data Exchange (ETDEWEB)

    Kroposki, B.; Myers, D.; Emery, K.; Mrig, L. [National Renewable Energy Lab., Golden, CO (United States); Whitaker, C.; Newmiller, J. [Endecon Engineering, San Ramon, CA (United States)

    1996-05-01

    A consensus-based methodology to calculate the energy output of a PV module will be described in this paper. The methodology develops a simple measure of PV module performance that provides for a realistic estimate of how a module will perform in specific applications. The approach makes use of the weather data profiles that describe conditions throughout the United States and emphasizes performance differences between various module types. An industry-representative Technical Review Committee has been assembled to provide feedback and guidance on the strawman and final approach used in developing the methodology.

  11. Integrated Performance Testing Workshop, Modules 6 - 11

    Energy Technology Data Exchange (ETDEWEB)

    Leach, Janice; Torres, Teresa M.

    2012-10-01

    These modules cover performance testing of: Interior Detection Systems; Access Controls; Exterior Detection Systems; Video Assessment Systems; SNM / Contraband Detection Systems; Access Delay Elements

  12. Dense module enumeration in biological networks

    Science.gov (United States)

    Tsuda, Koji; Georgii, Elisabeth

    2009-12-01

    Analysis of large networks is a central topic in various research fields including biology, sociology, and web mining. Detection of dense modules (a.k.a. clusters) is an important step to analyze the networks. Though numerous methods have been proposed to this aim, they often lack mathematical rigorousness. Namely, there is no guarantee that all dense modules are detected. Here, we present a novel reverse-search-based method for enumerating all dense modules. Furthermore, constraints from additional data sources such as gene expression profiles or customer profiles can be integrated, so that we can systematically detect dense modules with interesting profiles. We report successful applications in human protein interaction network analyses.

  13. Dense module enumeration in biological networks

    International Nuclear Information System (INIS)

    Tsuda, Koji; Georgii, Elisabeth

    2009-01-01

    Analysis of large networks is a central topic in various research fields including biology, sociology, and web mining. Detection of dense modules (a.k.a. clusters) is an important step to analyze the networks. Though numerous methods have been proposed to this aim, they often lack mathematical rigorousness. Namely, there is no guarantee that all dense modules are detected. Here, we present a novel reverse-search-based method for enumerating all dense modules. Furthermore, constraints from additional data sources such as gene expression profiles or customer profiles can be integrated, so that we can systematically detect dense modules with interesting profiles. We report successful applications in human protein interaction network analyses.

  14. Cascaded Amplitude Modulations in Sound Texture Perception

    Directory of Open Access Journals (Sweden)

    Richard McWalter

    2017-09-01

    Full Text Available Sound textures, such as crackling fire or chirping crickets, represent a broad class of sounds defined by their homogeneous temporal structure. It has been suggested that the perception of texture is mediated by time-averaged summary statistics measured from early auditory representations. In this study, we investigated the perception of sound textures that contain rhythmic structure, specifically second-order amplitude modulations that arise from the interaction of different modulation rates, previously described as “beating” in the envelope-frequency domain. We developed an auditory texture model that utilizes a cascade of modulation filterbanks that capture the structure of simple rhythmic patterns. The model was examined in a series of psychophysical listening experiments using synthetic sound textures—stimuli generated using time-averaged statistics measured from real-world textures. In a texture identification task, our results indicated that second-order amplitude modulation sensitivity enhanced recognition. Next, we examined the contribution of the second-order modulation analysis in a preference task, where the proposed auditory texture model was preferred over a range of model deviants that lacked second-order modulation rate sensitivity. Lastly, the discriminability of textures that included second-order amplitude modulations appeared to be perceived using a time-averaging process. Overall, our results demonstrate that the inclusion of second-order modulation analysis generates improvements in the perceived quality of synthetic textures compared to the first-order modulation analysis considered in previous approaches.

  15. Parametric Amplification, Wavelength Conversion, and Phase Conjugation of a 2.048-Tbit/s WDM PDM 16-QAM Signal

    DEFF Research Database (Denmark)

    Hu, Hao; Jopson, R. M.; Gnauck, A. H.

    2015-01-01

    We demonstrate polarization-independent parametric amplification of a 2.048-Tbit/s 8-WDM PDM 16-QAM signal and simultaneous wavelength conversion and phase conjugation in a highly nonlinear fiber. Two high-power continuous-wave pumps with orthogonal polarizations and counter-phase modulation are ...

  16. Magnetic gating of a 2D topological insulator

    Science.gov (United States)

    Dang, Xiaoqian; Burton, J. D.; Tsymbal, Evgeny Y.

    2016-09-01

    Deterministic control of transport properties through manipulation of spin states is one of the paradigms of spintronics. Topological insulators offer a new playground for exploring interesting spin-dependent phenomena. Here, we consider a ferromagnetic ‘gate’ representing a magnetic adatom coupled to the topologically protected edge state of a two-dimensional (2D) topological insulator to modulate the electron transmission of the edge state. Due to the locked spin and wave vector of the transport electrons the transmission across the magnetic gate depends on the mutual orientation of the adatom magnetic moment and the current. If the Fermi energy matches an exchange-split bound state of the adatom, the electron transmission can be blocked due to the full back scattering of the incident wave. This antiresonance behavior is controlled by the adatom magnetic moment orientation so that the transmission of the edge state can be changed from 1 to 0. Expanding this consideration to a ferromagnetic gate representing a 1D chain of atoms shows a possibility to control the spin-dependent current of a strip of a 2D topological insulator by magnetization orientation of the ferromagnetic gate.

  17. Tic Modulation Using Sensory Tricks

    Directory of Open Access Journals (Sweden)

    Rebecca W. Gilbert

    2013-04-01

    Full Text Available Background: A sensory trick, or geste antagoniste, is defined as a physical gesture (such as a touch on a particular body part that mitigates the production of an involuntary movement. This phenomenon is most commonly described as a feature of dystonia. Here we present a case of successful modulation of tics using sensory tricks.Case Report:: A case report and video are presented. The case and video demonstrate a 19-year-old male who successfully controlled his tics with various sensory tricks.Discussion: It is underappreciated by movement disorder physicians that sensory tricks can play a role in tics. Introducing this concept to patients could potentially help in tic control. In addition, understanding the pathophysiological underpinnings of sensory tricks could help in the understanding of the pathophysiology of tics.

  18. Comparaison of Atlas Tilecal module

    CERN Document Server

    Batusov1, V; Gayde, J C; Khubua, J I; Lasseur, C; Lyablin, M V; Miralles-Verge, L; Nessi, Marzio; Rusakovitch, N A; Sissakian, A N; Topilin, N D

    2002-01-01

    The high precision assembly of a large experimental set-ups is of a principal necessity for the successful execution of the forthcoming LHC research program in the TeV-beams. The creation of an adequate Survey&Control METROLOGY METHODs are an essential part of the detector construction scenario. This work contains the dimension measurement data for ATLAS hadron calorimeter MODULE#8 (6m long, 22tons) which were obtained by LASER and by PHOTOGRAMMETRY methods. The comparative data analysis demonstrates the measurements agreement within ±70mm. It means these two clearly independent methods can be combined and lead to the rise of a new generation engineering culture: high precision metrology when precision assembly of large scale massive objects.

  19. SSD with generalized phase modulation

    International Nuclear Information System (INIS)

    Rothenberg, J.

    1996-01-01

    Smoothing by spectral dispersion (SSD) with standard frequency modulation (FM), although simple to implement, has the disadvantage that low spatial frequencies present in the spectrum of the target illumination are not smoothed as effectively as with a more general smoothing method (eg, induced spatial incoherence method). The reduced smoothing performance of standard FM-SSD can result in spectral power of the speckle noise at these low spatial frequencies as much as one order of magnitude larger than that achieved with a more general method. In fact, at small integration times FM-SSD has no smoothing effect at all for a broad band of low spatial frequencies. This effect may have important implications for both direct and indirect drive ICF

  20. Solar dynamic power module design

    Science.gov (United States)

    Secunde, Richard R.; Labus, Thomas L.; Lovely, Ronald G.

    1989-01-01

    Studies have shown that the use of solar dynamic (SD) power for the growth areas of the Space Station Freedom program will result in life cycle cost savings when compared to power supplied by photovoltaic sources. In the SD power module, a concentrator collects and focuses solar energy into a heat receiver which has integral thermal energy storage. A Power Conversion Unit (PCU) based on the closed Brayton cycle removes thermal energy from the receiver and converts that energy to electrical energy. Since the closed Brayton cycle is a single phase gas cycle, the conversion hardware (heat exchangers, turbine, compressor, etc.) can be designed for operation in low earth orbit, and tested with confidence in test facilities on earth before launch into space. The concentrator subassemblies will be aligned and the receiver/PCU/radiator combination completely assembled and charged with gas and cooling liquid on earth before launch to, and assembly on, orbit.

  1. Pharmacological modulation of arterial stiffness.

    LENUS (Irish Health Repository)

    Boutouyrie, Pierre

    2011-09-10

    Arterial stiffness has emerged as an important marker of cardiovascular risk in various populations and reflects the cumulative effect of cardiovascular risk factors on large arteries, which in turn is modulated by genetic background. Arterial stiffness is determined by the composition of the arterial wall and the arrangement of these components, and can be studied in humans non-invasively. Age and distending pressure are two major factors influencing large artery stiffness. Change in arterial stiffness with drugs is an important endpoint in clinical trials, although evidence for arterial stiffness as a therapeutic target still needs to be confirmed. Drugs that independently affect arterial stiffness include antihypertensive drugs, mostly blockers of the renin-angiotensin-aldosterone system, hormone replacement therapy and some antidiabetic drugs such as glitazones. While the quest continues for \\'de-stiffening drugs\\

  2. Interfacial modulation of urban affect

    DEFF Research Database (Denmark)

    Samson, Kristine

    Urban culture can increasingly be understood as interface culture (Munster) in which urban design, cultural institutions and architecture increasingly operate as affective interfaces distributing and mediating human perception, consumption and social encounters. As noted by Amin and Thrift (2002......, Massey 2006), they also exclude in depth social and human interaction. Through analysis of three examples of urban affective interfaces (The High Line in New York, Superkilen in Copenhagen and Stålsat By, Frederiksværk, the paper examines how affective urban interfaces modulate and mediate urban...... environments as bodily and sensorial experiences. It asks what is mediated through the interface – whether the. It also asks, what is excluded when urban environments become affective interfaces in the global networked city. Whereas urban interface collect and distribute the bodily and sensible in relational...

  3. ALICE Time of Flight Module

    CERN Multimedia

    The Time-Of-Flight system of ALICE consists of 90 such modules, each containing 15 or 19 Multigap Resistive Plate Chamber (MRPC) strips. This detector is used for identification of charged particles. It measures with high precision (50 ps) the time of flight of charged particles and therefore their velocity. The curvature of the particle trajectory inside the magnetic field gives the momentum, thus the particle mass is calculated and the particle is identified The MRPC is a stack of resistive glass plates, separated from each other by nylon fishing line. The mass production of the chambers (~1600, covering a surface of 150 m2) was done at INFN Bologna, while the first prototypes were bult at CERN.

  4. Development of GREET Catalyst Module

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Zhichao [Argonne National Lab. (ANL), Argonne, IL (United States). Energy Systems Division; Dunn, Jennifer B. [Argonne National Lab. (ANL), Argonne, IL (United States). Energy Systems Division; Cronauer, Donald C. [Argonne National Lab. (ANL), Argonne, IL (United States). Energy Systems Division

    2014-09-01

    Catalysts are critical inputs for many pathways that convert biomass into biofuels. Energy consumption and greenhouse gas (GHG) emissions during the production of catalysts and chemical inputs influence the life-cycle energy consumption, and GHG emissions of biofuels and need to be considered in biofuel life-cycle analysis (LCA). In this report, we develop energy and material flows for the production of three different catalysts (tar reforming, alcohol synthesis, Zeolite Socony Mobil-5 [ZSM-5]) and two chemicals (olivine, dimethyl ether of polyethylene glycol [DEPG]). These compounds and catalysts are now included in the Greenhouse Gases, Regulated Emissions and Energy Use in Transportation (GREET™) catalyst module. They were selected because they are consumed in existing U.S. Department of Energy (DOE) analyses of biofuel processes. For example, a thermochemical ethanol production pathway (indirect gasification and mixed alcohol synthesis) developed by the National Renewable Energy Laboratory (NREL) uses olivine, DEPG, and tar reforming and alcohol synthesis catalysts (Dutta et al., 2011). ZSM-5 can be used in biofuel production pathways such as catalytic upgrading of sugars into hydrocarbons (Biddy and Jones, 2013). Other uses for these compounds and catalysts are certainly possible. In this report, we document the data sources and methodology we used to develop material and energy flows for the catalysts and compounds in the GREET catalyst module. In Section 2 we focus on compounds used in the model Dutta et al. (2011) developed. In Section 3, we report material and energy flows associated with ZSM-5 production. Finally, in Section 4, we report results.

  5. Modulating wind power plant output using different frequency modulation components for damping grid oscillations

    DEFF Research Database (Denmark)

    2017-01-01

    A method, controller, wind power plant, and computer program product are disclosed for operating a wind power plant comprising a plurality of wind turbines, the wind power plant producing a plant power output. The method comprises receiving a modulation request signal indicating a requested...... modulation of the plant power output, the requested modulation specifying a modulation frequency. The method further comprises generating a respective power reference signal for each of at least two wind turbines of the plurality of wind turbines selected to fulfill the requested modulation, Each generated...... power reference signal includes a respective modulation component corresponding to a portion of the requested modulation and having a frequency different than the modulation frequency....

  6. Significantly High Modulation Efficiency of Compact Graphene Modulator Based on Silicon Waveguide.

    Science.gov (United States)

    Shu, Haowen; Su, Zhaotang; Huang, Le; Wu, Zhennan; Wang, Xingjun; Zhang, Zhiyong; Zhou, Zhiping

    2018-01-17

    We theoretically and experimentally demonstrate a significantly large modulation efficiency of a compact graphene modulator based on a silicon waveguide using the electro refractive effect of graphene. The modulation modes of electro-absorption and electro-refractive can be switched with different applied voltages. A high extinction ratio of 25 dB is achieved in the electro-absorption modulation mode with a driving voltage range of 0 V to 1 V. For electro-refractive modulation, the driving voltage ranges from 1 V to 3 V with a 185-pm spectrum shift. The modulation efficiency of 1.29 V · mm with a 40-μm interaction length is two orders of magnitude higher than that of the first reported graphene phase modulator. The realisation of phase and intensity modulation with graphene based on a silicon waveguide heralds its potential application in optical communication and optical interconnection systems.

  7. Control module and module for priority set-up for the CAMAC universal branch driver

    International Nuclear Information System (INIS)

    Nguen Fuk; Smirnov, V.A.

    1976-01-01

    Control module of BKD-871 universal branch driver operates as a controller in the control crate. This module performs synchronous data transmission to (from) the computer and shapes time signals for A-type controllers. The following regimes of data block transmission may be organized with the help of the control module: address scanning regime; repeated reference regime; stop regime. A priority driving module is required for organization of simultaneous operation from several control sources

  8. XPM-induced degradation of multilevel phase modulated channel caused by neighboring NRZ modulated channels

    DEFF Research Database (Denmark)

    Jensen, Jesper Bevensee; Schiellerup, G.; Peucheret, Christophe

    2008-01-01

    The impact of XPM from NRZ modulated channels on an 8-level phase modulated channel in a WDM system was investigated. Requirements on launch power are found. 400 km transmission was achieved with negligible penalty.......The impact of XPM from NRZ modulated channels on an 8-level phase modulated channel in a WDM system was investigated. Requirements on launch power are found. 400 km transmission was achieved with negligible penalty....

  9. VOA: a 2-d plasma physics code

    International Nuclear Information System (INIS)

    Eltgroth, P.G.

    1975-12-01

    A 2-dimensional relativistic plasma physics code was written and tested. The non-thermal components of the particle distribution functions are represented by expansion into moments in momentum space. These moments are computed directly from numerical equations. Currently three species are included - electrons, ions and ''beam electrons''. The computer code runs on either the 7600 or STAR machines at LLL. Both the physics and the operation of the code are discussed

  10. Genetic polymorphisms of cytochrome P450-1A2 (CYP1A2 among Emiratis.

    Directory of Open Access Journals (Sweden)

    Mohammad M Al-Ahmad

    Full Text Available Cytochrome P450 1A2 (CYP1A2 is one of the CYP450 mixed-function oxidase system that is of clinical importance due to the large number of drug interactions associated with its induction and inhibition. In addition, significant inter-individual differences in the elimination of drugs metabolized by CYP1A2 enzyme have been observed which are largely due to the highly polymorphic nature of CYP1A2 gene. However, there are limited studies on CYP1A2 phenotypes and CYP1A2 genotypes among Emiratis and thus this study was carried out to fill this gap. Five hundred and seventy six non-smoker Emirati subjects were asked to consume a soft drink containing caffeine (a non-toxic and reliable probe for predicting CYP1A2 phenotype and then provide a buccal swab along with a spot urine sample. Taq-Man Real Time PCR was used to determine the CYP1A2 genotype of each individual. Phenotyping was carried out by analyzing the caffeine metabolites using High Performance Liquid Chromatography (HPLC analysis. We found that 1.4%, 16.3% and 82.3% of the Emirati subjects were slow, intermediate and rapid CYP1A2 metabolizers, respectively. In addition, we found that 1.4% of the subjects were homozygote for derived alleles while 16.1% were heterozygote and 82.5% were homozygote for the ancestral allele. The genotype frequency of the ancestral allele, CYP1A2*1A/*1A, is the highest in this population, followed by CYP1A2 *1A/*1C and CYP1A2 *1A/*1K genotypes, with frequencies of 0.825, 0.102 and 0.058, respectively. The degree of phenotype/genotype concordance was equal to 81.6%. The CYP1A2*1C/*1C and CYP1A2*3/*3 genotypes showed significantly the lowest enzyme phenotypic activity. The frequency of slow activity CYP1A2 enzyme alleles is very low among Emiratis which correlates with the presence of low frequencies of derived alleles in CYP1A2 gene.

  11. Spectro-temporal modulation masking patterns reveal frequency selectivity.

    Science.gov (United States)

    Oetjen, Arne; Verhey, Jesko L

    2015-02-01

    The present study investigated the possibility that the human auditory system demonstrates frequency selectivity to spectro-temporal amplitude modulations. Threshold modulation depth for detecting sinusoidal spectro-temporal modulations was measured using a generalized masked threshold pattern paradigm with narrowband masker modulations. Four target spectro-temporal modulations were examined, differing in their temporal and spectral modulation frequencies: a temporal modulation of -8, 8, or 16 Hz combined with a spectral modulation of 1 cycle/octave and a temporal modulation of 4 Hz combined with a spectral modulation of 0.5 cycles/octave. The temporal center frequencies of the masker modulation ranged from 0.25 to 4 times the target temporal modulation. The spectral masker-modulation center-frequencies were 0, 0.5, 1, 1.5, and 2 times the target spectral modulation. For all target modulations, the pattern of average thresholds for the eight normal-hearing listeners was consistent with the hypothesis of a spectro-temporal modulation filter. Such a pattern of modulation-frequency sensitivity was predicted on the basis of psychoacoustical data for purely temporal amplitude modulations and purely spectral amplitude modulations. An analysis of separability indicates that, for the present data set, selectivity in the spectro-temporal modulation domain can be described by a combination of a purely spectral and a purely temporal modulation filter function.

  12. Preliminary results of cold fusion studies using a five module high current electrolytic cell (Paper No. A2)

    International Nuclear Information System (INIS)

    Nayar, M.G.; Mitra, S.K.; Raghunathan, P.; Krishnan, M.S.; Malhotra, S.K.; Gaonkar, D.G.; Sikka, S.K.; Shyam, A.; Chitra, V.

    1989-01-01

    A high current modular palladium-nickel electrolytic cell was designed and operated to observe cold fusion reactions. The cathode was made up of palladium (25 per cent)-silver and the anode was made up of porous nickel. Using NaOD in D 2 O (20 per cent) as an electrolyte, the electrolyser was operated continuously at a current of 60 to 65 amps and applied voltage of ∼ 12.5V. The deuterium and oxygen gases produced were carried out of the cell to a recombination unit consisting of burner and condenser. The resultant heavy water was recycled back to the electrolyser. Measurement of the neutron output and tritium content of the electrolyte during and after electrolysis conclusively showed occurrence of cold fusion reactions. Gross neutron to tritium yield ratio was observed to be ∼ 10 -9 which should be taken as a lower limit, because a considerable quantity of tritium carried away by the gas stream could not recovered and taken into account. (M.G.B.). 2 tabs., 2 figs

  13. A 2D Finite Element Modelling of Tritium Permeation Through Cooling Plates for The HCLL DEMO Blanket Module

    International Nuclear Information System (INIS)

    Gabriel, F.; Escuriol, Y.; Dabbene, F.; Salavy, J.F.; Giancarli, L.; Gastaldi, O.

    2006-01-01

    As the Tritium self sufficiency is one of the major challenges for fusion reactor, breeding blankets represent one of the major technological breakthroughs required from passing from ITER to the next step reactor, usually called DEMO. One of the two blanket concepts developed in the EU is the Helium Cooled Lithium Lead (HCLL) blanket which uses the eutectic Pb-15.7Li metal liquid as both breeder and neutron multiplier. The structures, made of EUROFER, a low activation ferritic martensitic steel, are cooled by pressurized helium at 8 MPa and inlet/outlet temperature 300/500 o C. In this concept, the LiPb is fed from the top of the blanket and distributed in parallel vertical channels among pairs of cells (one cell for the radial movement towards the plasma, the other for the return). The liquid metal fills the in-box volume and is slowly re-circulated (few mm per seconds) to remove the produced tritium. In this paper, a local finite element modelling of the tritium permeation rate through the HCLL breeder unit cooling plates is presented. The tritium concentration in the helium circuit and remaining in the lithium lead circuit are evaluated by solving partial differential equations governing the tritium concentration balance, the thermal field and the lithium lead velocity field for a simplified 2D geometrical representation of the breeder unit. This allows estimating the sensitivity effect of coupling these different equations in order to deduce a relevant but simplified modelling for tritium permeation. This is to compare with tritium inventories studies, were the tritium permeation rate is estimated using simplified analytical modelling which generally leads to over estimate the tritium permeation rate to the coolant and so has strong influence on the coolant purification plant design. The finite element modelling performed shows that the Tritium permeation is considerable lower than the one obtained in previous estimations where nominal values of the governing parameters were used. Using, as boundary conditions, efficiency of the external purification system, this analysis can be related and integrated in the global inventory analysis. One of the main consequences for the HCLL blanket design is that the requirements of T-permeation barrier performances can be significantly relaxed to a level already demonstrated by current barriers. (author)

  14. Modulating the level of components within plants

    Science.gov (United States)

    Bobzin, Steven Craig; Apuya, Nestor; Chiang, Karen; Doukhanina, Elena; Feldmann, Kenneth; Jankowski, Boris; Margolles-Clark, Emilio; Mumenthaler, Daniel; Okamuro, Jack; Park, Joon-Hyun; Van Fleet, Jennifer E.; Zhang, Ke

    2017-09-12

    Materials and Methods for identifying lignin regulatory region-regulatory protein associations are disclosed. Materials and methods for modulating lignin accumulation are also disclosed. In addition, methods and materials for modulating (e.g., increasing or decreasing) the level of a component (e.g., protein, oil, lignin, carbon, a carotenoid, or a triterpenoid) in plants are disclosed.

  15. An abstract machine for module replacement

    OpenAIRE

    Walton, Chris; Krl, Dilsun; Gilmore, Stephen

    1998-01-01

    In this paper we define an abstract machine model for the mλ typed intermediate language. This abstract machine is used to give a formal description of the operation of run-time module replacement from the programming language Dynamic ML. The essential technical device which we employ for module replacement is a modification of two-space copying garbage collection.

  16. Quantification of Shading Tolerability for Photovoltaic Modules

    NARCIS (Netherlands)

    Ziar, H.; Asaei, Behzad; Farhangi, Shahrokh; Isabella, O.; Korevaar, M.A.N.; Zeman, M.

    2017-01-01

    Despite several decades of research in the field of photovoltaic (PV) systems, shading tolerance has still not been properly addressed. PV modules are influenced by shading concerning many factors, such as number and configuration of cells in the module, electrical and thermal characteristics of

  17. Multicarrier Modulation Techniques for 5G Communications

    OpenAIRE

    QIANYU JIN

    2018-01-01

    This thesis focuses on multicarrier modulation techniques for 5G wireless communications. We study different properties of current multicarrier modulation techniques and propose methodologies to improve them in order to meet the demands of 5G wireless, e.g., low out-of-band radiation, low latency, relaxed synchronization, and stable performance against phase noise with low complexity over a wireless channel.

  18. Some Model Theoretic Remarks on Bass Modules

    Directory of Open Access Journals (Sweden)

    E. Momtahan

    2011-09-01

    Full Text Available We study Bass modules, Bass rings, and related concepts from a model theoretic point of view. We observe that the class of Bass modules (over a fixed ring is not stable under elementary equivalence. We observe that under which conditions the class of Bass rings are stable under elementary equivalence.

  19. Research: Designing interprofessional modules for undergraduate ...

    African Journals Online (AJOL)

    ... financial constraints, administrative support, logistical issues and resistance to change. The designing and implementing of new modules were intense and time consuming, and required commitment. The development of the modules was an excellent example of interprofessional teamwork that needs to be transferred to ...

  20. 2015 NREL Photovoltaic Module Reliability Workshops

    Energy Technology Data Exchange (ETDEWEB)

    Kurtz, Sarah [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2017-09-14

    NREL's Photovoltaic (PV) Module Reliability Workshop (PVMRW) brings together PV reliability experts to share information, leading to the improvement of PV module reliability. Such improvement reduces the cost of solar electricity and promotes investor confidence in the technology--both critical goals for moving PV technologies deeper into the electricity marketplace.