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Sample records for bradykinin b2 receptor

  1. Kallikrein activates bradykinin B2 receptors in absence of kininogen.

    Science.gov (United States)

    Biyashev, Dauren; Tan, Fulong; Chen, Zhenlong; Zhang, Kai; Deddish, Peter A; Erdös, Ervin G; Hecquet, Claudie

    2006-03-01

    Kallikreins cleave plasma kininogens to release the bioactive peptides bradykinin (BK) or kallidin (Lys-BK). These peptides then activate widely disseminated B2 receptors with consequences that may be either noxious or beneficial. We used cultured cells to show that kallikrein can bypass kinin release to activate BK B2 receptors directly. To exclude intermediate kinin release or kininogen uptake from the cultured medium, we cultured and maintained cells in medium entirely free of animal proteins. We compared the responses of stably transfected Chinese hamster ovary (CHO) cells that express human B2 receptors (CHO B2) and cells that coexpress angiotensin I-converting enzyme (ACE) as well (CHO AB). We found that BK (1 nM or more) and tissue kallikrein (1-10 nM) both significantly increased release of arachidonic acid beyond unstimulated baseline level. An enzyme-linked immunoassay for kinin established that kallikrein did not release a kinin from CHO cells. We confirmed the absence of kininogen mRNA with RT-PCR to rule out kininogen synthesis by CHO cells. We next tested an ACE inhibitor for enhanced BK receptor activation in the absence of kinin release and synthesized an ACE-resistant BK analog as a control for these experiments. Enalaprilat (1 microM) potentiated kallikrein (100 nM) in CHO AB cells but was ineffective in CHO B2 cells that do not bear ACE. We concluded that kallikrein activated B2 receptors without releasing a kinin. Furthermore, inhibition of ACE enhanced the receptor activation by kallikrein, an action that may contribute to the manifold therapeutic effects of ACE inhibitors. PMID:16272198

  2. Advanced Modelling and Functional Characterization of B2 Bradykinin Receptor

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    Muhammad Saad Khan

    2015-06-01

    Full Text Available Hereditary angioedema (giant hives is an autosomal dominant malady characterized by repetitive episodes of probably life-threatening angioedema due to a partial deficiency of C1 inhibitor. B2 Bradykinin Receptor's (BKRB2 amino acid sequence is deposited within UniProt under accession number P30411. The Physicochemical properties of BKRB2 sequence are determined by using ProtParam. BKRB2's secondary structure was predicted through PROTEUS. Pfam domain was used for functional characterization of BKRB2. PSI-BLAST was used to find homologs of known structure. Modelling by satisfaction of spatial restraints, either uses distance geometry or optimization techniques to satisfy spatial restraints performed by MODELLER. The quality of the generated model was evaluated with PROCHECK by Ramachandran plot analysis. Validation of the generated models was further performed by WHAT IF. ProSA was used for the analysis of Z-scores and energy plots. The 3D structures of the modeled proteins were analyzed using UCSF Chimera. Clustal Omega is used for multiple sequence alignment that uses seeded guide trees and HMM profile-profile techniques to generate alignments.

  3. The angiotensin II type 1 receptor antagonist Losartan binds and activates bradykinin B2 receptor signaling

    DEFF Research Database (Denmark)

    Bonde, Marie Mi; Olsen, Kristine Boisen; Erikstrup, Niels;

    2011-01-01

    The angiotensin II type 1 receptor (AT1R) blocker (ARB) Losartan has cardioprotective effects during ischemia-reperfusion injury and inhibits reperfusion arrhythmias -effects that go beyond the benefits of lowering blood pressure. The renin-angiotensin and kallikrein-kinin systems are intricately...... connected and some of the cardioprotective effects of Losartan are abolished by blocking the bradykinin B2 receptor (B2R) signaling. In this study, we investigated the ability of six clinically available ARBs to specifically bind and activate the B2R. First, we investigated their ability to activate...... phosphoinositide (PI) hydrolysis in COS-7 cells transiently expressing the B2R. We found that only Losartan activated the B2R, working as a partial agonist compared to the endogenous ligand bradykinin. This effect was blocked by the B2R antagonist HOE 140. A competitive binding analysis revealed that Losartan does...

  4. Kallikrein activates bradykinin B2 receptors in the absence of kininogen

    OpenAIRE

    Biyashev, Dauren; Tan, Fulong; Chen, Zhenlong; Zhang, Kai; Deddish, Peter A.; Erdös, Ervin G.; Hecquet, Claudie

    2005-01-01

    Kallikreins cleave plasma kininogens to release the bioactive peptides bradykinin (BK) or kallidin (Lys-BK). These peptides then activate widely disseminated B2 receptors with consequences that may be either noxious or beneficial. We used cultured cells to show that kallikrein can bypass kinin release to activate BK B2 receptors directly. To exclude intermediate kinin release or kininogen uptake from the culture medium, we cultured and maintained cells in medium entirely free of animal protei...

  5. Positive cooperativity between the thrombin and bradykinin B2 receptors enhances arachidonic acid release

    OpenAIRE

    Hecquet, Claudie; Biyashev, Dauren; Tan, Fulong; Erdös, Ervin G.

    2005-01-01

    Bradykinin (BK) or kallikreins activate B2 receptors (R) which couple Gαi and Gαq proteins to release arachidonic acid (AA) and elevate [Ca2+]i. Thrombin cleaves the protease-activated-receptor-1 (PAR1) that couples Gαi, Gαq and Gα12/13 proteins. In CHO cells stably transfected with human B2R, thrombin liberated little AA, but it significantly potentiated AA release by B2R agonists. We explored mechanisms of cooperativity between constitutively expressed PAR1 and B2R. We also examined human e...

  6. Close association of B2 bradykinin receptors with P2Y2 ATP receptors.

    Science.gov (United States)

    Yashima, Sayo; Shimazaki, Ayaka; Mitoma, Junya; Nakagawa, Tetsuto; Abe, Maya; Yamada, Hiroyuki; Higashi, Hideyoshi

    2015-08-01

    Two G-protein-coupled receptors (GPCRs) that couple with Gαq/11, B2 bradykinin (BK) receptor (B2R) and ATP/UTP receptor P2Y2 (P2Y2R), are ubiquitously expressed and responsible for vascular tone, inflammation, and pain. We analysed the cellular signalling of P2Y2Rs in cells that express B2Rs. B2R desensitization induced by BK or B2R internalization-inducing glycans cross-desensitized the P2Y2R response to ATP/UTP. Fluorescence resonance energy transfer from P2Y2R-AcGFP to B2R-DsRed was detected in the cells and on the cell surfaces, showing the close association of these GPCRs. BK- and ATP-induced cross-internalization of P2Y2R and B2R, respectively, was shown in a β-galactosidase complementation assay using P2Y2R or B2R fused to the H31R substituted α donor peptide of a β-galactosidase reporter enzyme (P2Y2R-α or B2R-α) with coexpression of the FYVE domain of endofin, an early endosome protein, fused to the M15 acceptor deletion mutant of β-galactosidase (the ω peptide, FYVE-ω). Arrestin recruitment to the GPCRs by cross-activation was also shown with the similar way. Coimmunoprecipitation showed that B2R and P2Y2R were closely associated in the cotransfected cells. These results indicate that B2R couples with P2Y2R and that these GPCRs act together to fine-tune cellular responsiveness. The collaboration between these receptors may permit rapid onset and turning off of biological events. PMID:25713410

  7. Human bradykinin B(2) receptor is activated by kallikrein and other serine proteases.

    Science.gov (United States)

    Hecquet, C; Tan, F; Marcic, B M; Erdös, E G

    2000-10-01

    Bradykinin (BK) and kallidin (Lys-BK), liberated from kininogens by kallikreins, are ligands of the BK B(2) receptor. We investigated whether kallikreins, besides releasing peptide agonist, could also activate the receptor directly. We studied the effect of porcine and human recombinant tissue kallikrein and plasma kallikrein on [Ca(2+)](i) mobilization and [(3)H]arachidonic acid release from cultured cells stably transfected to express human BK B(2) receptor (CHO/B(2), MDCK/B(2), HEK/B(2)), and endothelial cells were used as control cells. As with BK, the actions of kallikrein were blocked by the B(2) antagonist, HOE 140. Kallikrein was inactive on cells lacking B(2) receptor. Kallikrein and BK desensitized the receptor homologously but there was no cross-desensitization. Furthermore, 50 nM human cathepsin G and 50 nM trypsin also activated the receptor; this also was blocked by HOE 140. Experiments excluded a putative kinin release by proteases. [(3)H]AA release by BK was reduced by 40% by added kininase I (carboxypeptidase M); however, receptor activation by tissue kallikrein, trypsin, or cathepsin G was not affected. Prokallikrein and inhibited kallikrein were inactive, suggesting cleavage of a peptide bond in the receptor. Kallikreins were active on mutated B(2) receptor missing the 19 N-terminal amino acids, suggesting a type of activation different from that of thrombin receptor. Paradoxically, tissue kallikreins decreased the [(3)H]BK binding to the receptor with a low K(D) (3 nM) and inhibited it 78%. Thus, kallikreins and some other proteases activate human BK B(2) receptor directly, independent of BK release. The BK B(2) receptor may belong to a new group of serine protease-activated receptors. PMID:10999954

  8. Reduction of sodium deoxycholic acid-induced scratching behaviour by bradykinin B2 receptor antagonists

    OpenAIRE

    Hayashi, Izumi; Majima, Masataka

    1999-01-01

    Subcutaneous injection of sodium deoxycholic acid into the anterior of the back of male ddY mice elicited dose-dependent scratching of the injected site with the forepaws and hindpaws.Up to 100 μg of sodium deoxycholic acid induced no significant increase in vascular permeability at the injection site as assessed by a dye leakage method.Bradykinin (BK) B2 receptor antagonists, FR173657 and Hoe140, significantly decreased the frequency of scratching induced by sodium deoxycholic acid.Treatment...

  9. Kallikreins when activating bradykinin B2 receptor induce its redistribution on plasma membrane.

    Science.gov (United States)

    Hecquet, Claudie; Becker, Robert P; Tan, Fulong; Erdös, Ervin G

    2002-12-01

    The bradykinin (BK) B2 receptor (R) is directly activated by kallikreins and other serine proteases independent of BK release. Both the Galpha(i) and Galpha(q) proteins are involved, shown by the release of arachidonic acid and [Ca2+]i elevation. Site-directed mutagenesis of the receptor and the lack of heterogeneous desensitization of the human B2R by the BK and kallikrein emphasize among others the differences between activation by the proteases and the peptide. To characterize further the mechanism thereby kallikreins activate and desensitize the B2R we investigated the distribution of the human B2R tagged with the green fluorescent protein (B2-GFP(Ct)) on the plasma membrane of stably transfected Chinese hamster ovary (CHO) cells. We visualized the movement of B2-GFP(Ct) R with confocal fluorescence microscopy after activation by BK or a by serine protease. Continued exposure of the cells to BK led to B2R internalization within 15-20 min. Porcine pancreatic and human recombinant tissue kallikreins induced a rapid definite redistribution of receptors on the plasma membrane within 5 min, prior to internalization. These effects of kallikrein were blocked by the B2R antagonist HOE 140 and by the kallikrein inhibitor, aprotinin. The B2R was also activated by endoproteinases LysC and ArgC and trypsin, but these enzymes did not induce redistribution, only internalization. In control experiments, kallikrein had no effect on cells transfected to stably express the angiotensin-converting enzyme-green fluorescent protein (GFP). Thus, kallikreins when activating the BK B2R also trigger its redistribution on plasma membrane. PMID:12489794

  10. Kallikrein activates bradykinin B2 receptors in the absence of kininogen

    Science.gov (United States)

    Biyashev, Dauren; Tan, Fulong; Chen, Zhenlong; Zhang, Kai; Deddish, Peter A.; Erdös, Ervin G.; Hecquet, Claudie

    2006-01-01

    Kallikreins cleave plasma kininogens to release the bioactive peptides bradykinin (BK) or kallidin (Lys-BK). These peptides then activate widely disseminated B2 receptors with consequences that may be either noxious or beneficial. We used cultured cells to show that kallikrein can bypass kinin release to activate BK B2 receptors directly. To exclude intermediate kinin release or kininogen uptake from the culture medium, we cultured and maintained cells in medium entirely free of animal proteins. We compared the responses of stably transfected CHO cells that express human B2 receptors (CHO-B2) and cells that co-express angiotensin I-converting enzyme (ACE) as well (CHO AB). We found that BK (1 nM or more) and tissue kallikrein (1–10 nM) both significantly increased release of arachidonic acid beyond unstimulated or baseline levels. An enzyme-linked immunoassay for kinin established that kallikrein did not release a kinin from CHO cells. We confirmed the absence of kininogen mRNA with RT-PCR to rule out kininogen synthesis by CHO cells. Next, we tested an ACE inhibitor for enhanced BK receptor activation in the absence of kinin release and synthesized an ACE-resistant BK analogue as a control for these experiments. Enalaprilat (1μM) potentiated kallikrein (100 nM) in CHO AB cells but was ineffective in CHO B2 cells that do not bear ACE. We concluded that kallikrein activated B2 receptors without releasing a kinin. Furthermore, inhibition of ACE enhanced the receptor activation by kallikrein, an action that may contribute to the manifold therapeutic effects of ACE inhibitors. PMID:16272198

  11. Positive cooperativity between the thrombin and bradykinin B2 receptors enhances arachidonic acid release.

    Science.gov (United States)

    Hecquet, Claudie; Biyashev, Dauren; Tan, Fulong; Erdös, Ervin G

    2006-03-01

    Bradykinin (BK) or kallikreins activate B2 receptors (R) that couple Galpha(i) and Galpha(q) proteins to release arachidonic acid (AA) and elevate intracellular Ca2+ concentration ([Ca2+]i). Thrombin cleaves the protease-activated-receptor-1 (PAR1) that couples Galpha(i), Galpha(q), and Galpha(12/13) proteins. In Chinese hamster ovary cells stably transfected with human B2R, thrombin liberated little AA, but it significantly potentiated AA release by B2R agonists. We explored mechanisms of cooperativity between constitutively expressed PAR1 and B2R. We also examined human endothelial cells expressing both Rs constitutively. The PAR1 agonist hexapeptide (TRAP) was as effective as thrombin. Inhibitors of components of Galpha(i), Galpha(q), and Galpha(12/13) signaling pathways, and a protein kinase C (PKC)-alpha inhibitor, Gö-6976, blocked potentiation, while phorbol, an activator, enhanced it. Several inhibitors, including a RhoA kinase inhibitor, a [Ca2+]i antagonist, and an inositol-(1,3,4)-trisphosphate R antagonist, reduced mobilization of [Ca2+]i by thrombin and blocked potentiation of AA release by B2R agonists. Because either a nonselective inhibitor (isotetrandrine) of phospholipase A2 (PLA2) or a Ca2+-dependent PLA2 inhibitor abolished potentiation of AA release by thrombin, while a Ca2+-independent PLA2 inhibitor did not, we concluded that the mechanism involves Ca2+-dependent PLA2 activation. Both thrombin and TRAP modified activation and phosphorylation of the B2R induced by BK. In lower concentrations they enhanced it, while higher concentrations inhibited phosphorylation and diminished B2R activation. Protection of the NH2-terminal Ser1-Phe2 bond of TRAP by an aminopeptidase inhibitor made this peptide much more active than the unprotected agonist. Thus PAR1 activation enhances AA release by B2R agonists through signal transduction pathway. PMID:16183725

  12. Positive cooperativity between the thrombin and bradykinin B2 receptors enhances arachidonic acid release

    Science.gov (United States)

    Hecquet, Claudie; Biyashev, Dauren; Tan, Fulong; Erdös, Ervin G.

    2006-01-01

    Bradykinin (BK) or kallikreins activate B2 receptors (R) which couple Gαi and Gαq proteins to release arachidonic acid (AA) and elevate [Ca2+]i. Thrombin cleaves the protease-activated-receptor-1 (PAR1) that couples Gαi, Gαq and Gα12/13 proteins. In CHO cells stably transfected with human B2R, thrombin liberated little AA, but it significantly potentiated AA release by B2R agonists. We explored mechanisms of cooperativity between constitutively expressed PAR1 and B2R. We also examined human endothelial cells expressing both Rs constitutively. The PAR1 agonist hexapeptide (TRAP) was as effective as thrombin. Inhibitors of components of Gαi, Gαq and Gα12/13 signaling pathways, and a PKCα inhibitor, Gö6976 blocked potentiation while phorbol, an activator, enhanced it. Several inhibitors, including a RhoA kinase inhibitor, a [Ca2+]i antagonist, and an inositol-(1,3,4)-trisphosphate R antagonist, reduced mobilization of [Ca2+]i by thrombin and blocked potentiation of AA release by B2R agonists. Because either a non-selective inhibitor (isotetrandrine) of phospholipase A2 (PLA2) or a Ca2+-dependent PLA2 inhibitor abolished potentiation of AA release by thrombin, while a Ca2+-independent PLA2 inhibitor did not, we concluded that the mechanism involves Ca2+-dependent PLA2 activation. Both thrombin and TRAP modified activation and phosphorylation of the B2R induced by BK. In lower concentrations they enhanced it, while higher concentrations inhibited phosphorylation and diminished B2R activation. Protection of the N-terminal Ser1-Phe2 bond of TRAP by an aminopeptidase inhibitor made this peptide much more active than the unprotected agonist. Thus, PAR1 activation enhances AA release by B2R agonists through signal transduction pathway. PMID:16183725

  13. Noradrenaline release from rat sympathetic neurones triggered by activation of B2 bradykinin receptors

    OpenAIRE

    Boehm, Stefan; Huck, Sigismund

    1997-01-01

    The role of bradykinin receptors in the regulation of sympathetic transmitter release was investigated in primary cultures of neurones dissociated from superior cervical ganglia of neonatal rats. These cultures were loaded with [3H]-noradrenaline and the outflow of radioactivity was determined under continuous superfusion.Bradykinin (100 nmol l−1 applied for 10 min) caused a transient increase in tritium outflow that reached a peak within four minutes after the beginning of the application an...

  14. In Vivo Effects of Bradykinin B2 Receptor Agonists with Varying Susceptibility to Peptidases

    Science.gov (United States)

    Jean, Mélissa; Gera, Lajos; Charest-Morin, Xavier; Marceau, François; Bachelard, Hélène

    2016-01-01

    We reported evidence of bradykinin (BK) regeneration from C-terminal extended BK sequences that behave as peptidase-activated B2 receptor (B2R) agonists. Further to these in vitro studies, we carried out in vivo experiments to verify hemodynamic effects of BK analogs exhibiting variable susceptibility toward vascular and blood plasma peptidases. Rats were anesthetized and instrumented to record blood pressure and heart rate responses to bolus intravenous (i.v.) injection of increasing doses of BK, B-9972 (D-Arg-[Hyp3,Igl5,Oic7,Igl8]-BK), BK-Arg, BK-His-Leu or BK-Ala-Pro, in the absence or presence of specific inhibitors. In some experiments, pulsed Doppler flow probes measured hindquarter Doppler shift in response to i.v. injections of kinins. BK caused rapid, transient and dose-related hypotensive effects. These effects were potentiated ∼15-fold by the angiotensin converting enzyme (ACE) inhibitor, enalaprilat, but extensively inhibited by icatibant (a B2R antagonist) and not influenced by the Arg-carboxypeptidase (CP) inhibitor (Plummer’s inhibitor). The hypotensive responses elicited by the peptidase-resistant B2R agonist, B-9972, were not affected by enalaprilat, but were inhibited by icatibant. The hypotensive responses to BK-Arg were abolished by pre-treatment with either the Arg-CP inhibitor or icatibant, pharmacologically evidencing BK regeneration. The hypotensive effects of BK-His-Leu and BK-Ala-Pro, previously reported as ACE-activated substrates, were abolished by icatibant, but not by enalaprilat. In vivo regeneration of BK from these two C-terminally extended analogs with no affinity for the B2R must follow alternative cleavage rules involving unidentified carboxypeptidase(s) when ACE is blocked. The transient hypotensive responses to BK and three tested analogs coincided with concomitant vasodilation (increased Doppler shift signal). Together, these results provide in vivo evidence that interesting hypotensive and vasodilator effects can be

  15. The B2 receptor of bradykinin is not essential for the post-exercise increase in glucose uptake by insulin-stimulated mouse skeletal muscle

    OpenAIRE

    Schweitzer, George G.; Castorena, Carlos M.; Hamada, Taku; Funai, Katsuhiko; Arias, Edward B.; Cartee, Gregory D.

    2011-01-01

    Bradykinin can enhance skeletal muscle glucose uptake (GU), and exercise increases both bradykinin production and muscle insulin sensitivity, but bradykinin’s relationship with post-exercise insulin action is uncertain. Our primary aim was to determine if the B2 receptor of bradykinin (B2R) is essential for the post-exercise increase in GU by insulin-stimulated mouse soleus muscles. Wildtype (WT) and B2R knockout (B2RKO) mice were sedentary or performed 60 minutes of treadmill exercise. Isola...

  16. Blood pressure in patients with primary aldosteronism is influenced by bradykinin B(2) receptor and alpha-adducin gene polymorphisms.

    Science.gov (United States)

    Mulatero, Paolo; Williams, Tracy A; Milan, Alberto; Paglieri, Cristina; Rabbia, Franco; Fallo, Francesco; Veglio, Franco

    2002-07-01

    Primary aldosteronism (PA) is the most common cause of endocrine hypertension. PA is most frequently presented as moderate to severe hypertension, but the clinical and biochemical features vary widely. The aim of our study was to identify genetic variants that influence the phenotype of patients with PA. We hypothesized that genetic variants potentially affecting aldosterone production (aldosterone synthase, CYP11B2), renal proximal tubule reabsorption (alpha-adducin), or the mechanisms of counterbalance leading to vasodilatation and sodium excretion (bradykinin B(2)-receptor, B(2)R) could influence the clinical and biochemical characteristics of patients with PA. We studied three polymorphisms of these genes (C-344T of CYP11B2, G460W of alpha-adducin, and C-58T of B(2)R) in 167 primary aldosteronism patients (56 with aldosterone-producing adenoma and 111 with idiopathic hyperaldosteronism). B(2)R and alpha-adducin genotypes were strong independent predictors of both systolic and diastolic blood pressure levels; plasma renin activity and aldosterone also play a marginal role on BP levels. Body mass index, age, sex, and CYP11B2 genotype displayed no significant effect on the clinical parameters of our population. In particular, alpha-adducin and B(2)R polymorphisms accounted for 13.2% and 11.0% of the systolic and diastolic blood pressure variance, respectively. These data suggest that genetic variants of alpha-adducin and the bradykinin B(2)-R influence the blood pressure levels in patients with primary aldosteronism. PMID:12107246

  17. Metabolically stable bradykinin B2 receptor agonists enhance transvascular drug delivery into malignant brain tumors by increasing drug half-life

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    Glen Daniel

    2009-05-01

    Full Text Available Abstract Background The intravenous co-infusion of labradimil, a metabolically stable bradykinin B2 receptor agonist, has been shown to temporarily enhance the transvascular delivery of small chemotherapy drugs, such as carboplatin, across the blood-brain tumor barrier. It has been thought that the primary mechanism by which labradimil does so is by acting selectively on tumor microvasculature to increase the local transvascular flow rate across the blood-brain tumor barrier. This mechanism of action does not explain why, in the clinical setting, carboplatin dosing based on patient renal function over-estimates the carboplatin dose required for target carboplatin exposure. In this study we investigated the systemic actions of labradimil, as well as other bradykinin B2 receptor agonists with a range of metabolic stabilities, in context of the local actions of the respective B2 receptor agonists on the blood-brain tumor barrier of rodent malignant gliomas. Methods Using dynamic contrast-enhanced MRI, the pharmacokinetics of gadolinium-diethyltriaminepentaacetic acid (Gd-DTPA, a small MRI contrast agent, were imaged in rodents bearing orthotopic RG-2 malignant gliomas. Baseline blood and brain tumor tissue pharmacokinetics were imaged with the 1st bolus of Gd-DTPA over the first hour, and then re-imaged with a 2nd bolus of Gd-DTPA over the second hour, during which normal saline or a bradykinin B2 receptor agonist was infused intravenously for 15 minutes. Changes in mean arterial blood pressure were recorded. Imaging data was analyzed using both qualitative and quantitative methods. Results The decrease in systemic blood pressure correlated with the known metabolic stability of the bradykinin B2 receptor agonist infused. Metabolically stable bradykinin B2 agonists, methionine-lysine-bradykinin and labradimil, had differential effects on the transvascular flow rate of Gd-DTPA across the blood-brain tumor barrier. Both methionine-lysine-bradykinin

  18. The relationship of Bradykinin B2 receptor gene variation with obesity, hypertension and lipid variables in obese patients

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    Nur Bakir

    2014-11-01

    Full Text Available Objective. This study examined the association of C-58T genotypes with obesity/hypertension related parameters and serum lipids in obese (n=108 and non-obese (n=80 patients. Materials and methods. Bradykinin receptor (B2R C-58T genotypes were determined by PCR–RFLP. Results. B2R gene C-58T frequencies for T/T (homozygous wild type, T/C (heterozygous and C/C (homozygous polymorphic genotypes for obese and non-obese patients were respectively: 36.1%, 37.5%; 45.4%, 52.5% and 18.5%, 10%. Obese patients using diuretic medication had lower C/C genotype frequency compared to T/T and T/C genotypes. Total cholesterol (T-Chol (p=0.035 levels were found to be associated with B2R C-58T polymorphism, where the T/T genotype had higher total cholesterol levels compared to the T/C genotype in obese patients. Non-obese patients using oral antidiabetic medication had higher C/C genotype frequency than that of T/T and T/C genotypes. Waist circumference (p=0.016 and diastolic blood pressure (p=0.01 levels were elevated in the non-obese subjects with the C/C genotype compared to T/C and T/T. Conclusion. Although B2R C-58T gene polymorphism was not found to be effective on obesity with logistic regression analysis in the whole study population in obese subjects, the T-Chol decreasing effect of the B2R gene C allele and the higher waist circumference measurements in the non-obese subjects may indicate there may be a link between B2R gene C-58T polymorphism and obesity in study populations of higher numbers.

  19. The bradykinin B2 receptor induces multiple cellular responses leading to the proliferation of human renal carcinoma cell lines

    International Nuclear Information System (INIS)

    The vasoactive peptide bradykinin (BK) acts as a potent growth factor for normal kidney cells, but there have been few studies on the role of BK in renal cell carcinomas. In this study, we tested the hypothesis that BK also acts as a mitogen in kidney carcinomas, and explored the effects of BK in human renal carcinoma A498 cells. The presence of mRNAs for BK B1 and BK B2 receptors in A498 cells was demonstrated by reverse transcription–polymerase chain reaction. To study BK signaling pathways, we employed fluorescent measurements of intracellular Ca2+, measured changes in extracellular pH as a reflection of Na+/H+ exchange (NHE) with a Cytosensor microphysiometer, and assessed extracellular signal-regulated kinase (ERK) activation by Western blotting. Exposure to 100 nM of BK resulted in the rapid elevation of intracellular Ca2+, caused a ≥30% increase in NHE activity, and a ≥300% increase in ERK phosphorylation. All BK signals were blocked by HOE140, a BK B2 receptor antagonist, but not by a B1 receptor antagonist. Inhibitor studies suggest that BK-induced ERK activation requires phospholipase C and protein kinase C activities, and is Ca2+/calmodulin-dependent. The amiloride analog 5-(N-methyl-N-isobutyl)-amiloride (MIA) blocked short-term NHE activation and inhibited ERK phosphorylation, suggesting that NHE is critical for ERK activation by BK. BK induced an approximately 40% increase in the proliferation of A498 cells as assessed by bromodeoxyuridine uptake. This effect was blocked by the ERK inhibitor PD98059, and was dependent on NHE activity. We conclude that BK exerts mitogenic effects in A498 cells via the BK B2 receptor activation of growth-associated NHE and ERK

  20. The bradykinin B2 receptor induces multiple cellular responses leading to the proliferation of human renal carcinoma cell lines

    Directory of Open Access Journals (Sweden)

    Kramarenko II

    2012-07-01

    Full Text Available Inga I Kramarenko1, Thomas A Morinelli1,2, Marlene A Bunni1,2, John R Raymond Sr3, Maria N Garnovskaya11Department of Medicine (Nephrology Division, Medical University of South Carolina, Charleston, SC, USA; 2Medical and Research Services of the Ralph H Johnson Veterans Affairs Medical Center, Charleston, SC, USA; 3Medical College of Wisconsin, Milwaukee, WI, USABackground: The vasoactive peptide bradykinin (BK acts as a potent growth factor for normal kidney cells, but there have been few studies on the role of BK in renal cell carcinomas.Purpose: In this study, we tested the hypothesis that BK also acts as a mitogen in kidney carcinomas, and explored the effects of BK in human renal carcinoma A498 cells.Methods: The presence of mRNAs for BK B1 and BK B2 receptors in A498 cells was demonstrated by reverse transcription–polymerase chain reaction. To study BK signaling pathways, we employed fluorescent measurements of intracellular Ca2+, measured changes in extracellular pH as a reflection of Na+/H+ exchange (NHE with a Cytosensor microphysiometer, and assessed extracellular signal-regulated kinase (ERK activation by Western blotting.Results: Exposure to 100 nM of BK resulted in the rapid elevation of intracellular Ca2+, caused a ≥30% increase in NHE activity, and a ≥300% increase in ERK phosphorylation. All BK signals were blocked by HOE140, a BK B2 receptor antagonist, but not by a B1 receptor antagonist. Inhibitor studies suggest that BK-induced ERK activation requires phospholipase C and protein kinase C activities, and is Ca2+/calmodulin-dependent. The amiloride analog 5-(N-methyl-N-isobutyl-amiloride (MIA blocked short-term NHE activation and inhibited ERK phosphorylation, suggesting that NHE is critical for ERK activation by BK. BK induced an approximately 40% increase in the proliferation of A498 cells as assessed by bromodeoxyuridine uptake. This effect was blocked by the ERK inhibitor PD98059, and was dependent on NHE activity

  1. Risk of bradykinin B2 receptor -58T/C gene polymorphism on hypertension: A meta-analysis.

    Science.gov (United States)

    Luo, Kaiping; Yang, Pingping; Xu, Gaosi

    2016-08-01

    The risk of bradykinin B2 receptor (BDKRB2)-58T/C gene polymorphism on hypertension remains controversial. The Cochrane Library, Chinese Biomedical Database, EBSCO, Embase, ISI, MEDLINE, and PubMed were retrieved, and relevant articles were selected. The significant association between BDKRB2 -58T/C gene polymorphism and risk of hypertension were found under C-allele comparison (odds ratio (OR): 1.22, 95% confidential intervals (CI): 1.05-1.42), recessive model (OR: 1.32, 95% CI: 1.07-1.64), dominant model (OR: 0.74, 95% CI: 0.58-0.94), homozygote model (OR: 1.66, 95% CI: 1.11-2.47) and heterozygote model (OR: 1.23, 95% CI: 1.06-1.43). The magnitude of the association between the BDKRB2-58T/C gene polymorphism and risk of hypertension was substantiated in Asians under C-allele comparison (OR: 1.24, 95% CI: 1.04-1.49), recessive model (OR: 1.39, 95% CI: 1.04-1.86), dominant model (OR: 0.72, 95% CI: 0.56-0.93), homozygote model (OR: 1.78, 95% CI: 1.09-2.90) and heterozygote model (OR: 1.26, 95% CI: 1.07-1.49). No publication bias was found in the meta-analysis. The meta-analysis suggested -58C allele and -58CC genotype increase the risk of hypertension in Asians and African-Americans. Inversely, -58TT genotype decreases the risk of hypertension in Asians and African-Americans. PMID:27007662

  2. Bradykinin inhibits development of myocardial infarction through B2 receptor signalling by increment of regional blood flow around the ischaemic lesions in rats

    OpenAIRE

    Ito, Hiroshi; Hayashi, Izumi; Izumi, Tohru; Majima, Masataka

    2003-01-01

    To identify the roles of endogenous kinins in prevention of myocardial infarction (MI), we performed the permanent ligation of coronary artery in rats.The size of MI 12, 24, and 48 h after coronary ligation in kininogen-deficient Brown Norway Katholiek (BN-Ka) rats was significantly larger (49.7±0.2%, 49.6±2%, and 51.1±1%, respectively) than that of kinin-replete Brown Norway Kitasato (BN-Ki) rats (42±2%, 38.5±4%, and 41.5±1%).Hoe140, a bradykinin (BK) B2 receptor antagonist injected (1.0 mg ...

  3. A cleavable signal peptide enhances cell surface delivery and heterodimerization of Cerulean-tagged angiotensin II AT1 and bradykinin B2 receptor

    International Nuclear Information System (INIS)

    Highlights: → A new FRET-based method detects AT1/B2 receptor heterodimerization. → First time application of AT1-Cerulean as a FRET donor. → Method relies on signal peptide-enhanced cell surface delivery of AT1-Cerulean. → A high FRET efficiency revealed efficient heterodimerization of AT1/B2R proteins. → AT1/B2R heterodimers were functionally coupled to desensitization mechanisms. -- Abstract: Heterodimerization of the angiotensin II AT1 receptor with the receptor for the vasodepressor bradykinin, B2R, is known to sensitize the AT1-stimulated response of hypertensive individuals in vivo. To analyze features of that prototypic receptor heterodimer in vitro, we established a new method that uses fluorescence resonance energy transfer (FRET) and applies for the first time AT1-Cerulean as a FRET donor. The Cerulean variant of the green fluorescent protein as donor fluorophore was fused to the C-terminus of AT1, and the enhanced yellow fluorescent protein (EYFP) as acceptor fluorophore was fused to B2R. In contrast to AT1-EGFP, the AT1-Cerulean fusion protein was retained intracellularly. To facilitate cell surface delivery of AT1-Cerulean, a cleavable signal sequence was fused to the receptor's amino terminus. The plasma membrane-localized AT1-Cerulean resembled the native AT1 receptor regarding ligand binding and receptor activation. A high FRET efficiency of 24.7% between membrane-localized AT1-Cerulean and B2R-EYFP was observed with intact, non-stimulated cells. Confocal FRET microscopy further revealed that the AT1/B2 receptor heterodimer was functionally coupled to receptor desensitization mechanisms because activation of the AT1-Cerulean/B2R-EYFP heterodimer with a single agonist triggered the co-internalization of AT1/B2R. Receptor co-internalization was sensitive to inhibition of G protein-coupled receptor kinases, GRKs, as evidenced by a GRK-specific peptide inhibitor. In agreement with efficient AT1/B2R heterodimerization, confocal FRET imaging of

  4. A cleavable signal peptide enhances cell surface delivery and heterodimerization of Cerulean-tagged angiotensin II AT1 and bradykinin B2 receptor

    Energy Technology Data Exchange (ETDEWEB)

    Quitterer, Ursula, E-mail: ursula.quitterer@pharma.ethz.ch [Molecular Pharmacology Unit, Swiss Federal Institute of Technology and University of Zurich, Zurich (Switzerland); Pohl, Armin; Langer, Andreas; Koller, Samuel; AbdAlla, Said [Molecular Pharmacology Unit, Swiss Federal Institute of Technology and University of Zurich, Zurich (Switzerland)

    2011-06-10

    Highlights: {yields} A new FRET-based method detects AT1/B2 receptor heterodimerization. {yields} First time application of AT1-Cerulean as a FRET donor. {yields} Method relies on signal peptide-enhanced cell surface delivery of AT1-Cerulean. {yields} A high FRET efficiency revealed efficient heterodimerization of AT1/B2R proteins. {yields} AT1/B2R heterodimers were functionally coupled to desensitization mechanisms. -- Abstract: Heterodimerization of the angiotensin II AT1 receptor with the receptor for the vasodepressor bradykinin, B2R, is known to sensitize the AT1-stimulated response of hypertensive individuals in vivo. To analyze features of that prototypic receptor heterodimer in vitro, we established a new method that uses fluorescence resonance energy transfer (FRET) and applies for the first time AT1-Cerulean as a FRET donor. The Cerulean variant of the green fluorescent protein as donor fluorophore was fused to the C-terminus of AT1, and the enhanced yellow fluorescent protein (EYFP) as acceptor fluorophore was fused to B2R. In contrast to AT1-EGFP, the AT1-Cerulean fusion protein was retained intracellularly. To facilitate cell surface delivery of AT1-Cerulean, a cleavable signal sequence was fused to the receptor's amino terminus. The plasma membrane-localized AT1-Cerulean resembled the native AT1 receptor regarding ligand binding and receptor activation. A high FRET efficiency of 24.7% between membrane-localized AT1-Cerulean and B2R-EYFP was observed with intact, non-stimulated cells. Confocal FRET microscopy further revealed that the AT1/B2 receptor heterodimer was functionally coupled to receptor desensitization mechanisms because activation of the AT1-Cerulean/B2R-EYFP heterodimer with a single agonist triggered the co-internalization of AT1/B2R. Receptor co-internalization was sensitive to inhibition of G protein-coupled receptor kinases, GRKs, as evidenced by a GRK-specific peptide inhibitor. In agreement with efficient AT1/B2R

  5. Antioxidant/oxidant status and cardiac function in bradykinin B(1)- and B(2)-receptor null mice.

    Science.gov (United States)

    Delemasure, S; Blaes, N; Richard, C; Couture, R; Bader, M; Dutartre, P; Girolami, J-P; Connat, J-L; Rochette, L

    2013-01-01

    Kinin-vasoactive peptides activate two G-protein-coupled receptors (R), B(1)R (inducible) and B(2)R (constitutive). Their complex role in cardiovascular diseases could be related to differential actions on oxidative stress. This study investigated impacts of B(1)R or B(2)R gene deletion in mice on the cardiac function and plasma antioxidant and oxidant status. Echocardiography-Doppler was performed in B(1)R (B(1)R(-/-)) and B(2)R (B(2)R(-/-)) deficient and wild type (WT) adult male mice. No functional alteration was observed in B(2)R(-/-) hearts. B(1)R(-/-) mice had significantly lowered fractional shortening and increased isovolumetric contraction time. The diastolic E and A waves velocity ratio was similar in all mice groups. Thus B(1)R(-/-) mice provide a model of moderate systolic dysfunction, whereas B(2)R(-/-) mice displayed a normal cardiac phenotype. Plasma antioxidant capacity (ORAC) was significantly decreased in both B(1)R(-/-) and B(2)R(-/-) mice whereas the vitamin C levels were decreased in B(2)R(-/-) mice only. Plasma ascorbyl free radical was significantly higher in B(1)R(-/-) compared to WT and B(2)R(-/-) mice. Therefore, the oxidative stress index, ascorbyl free radical to vitamin C ratio, was increased in both B(1)R(-/-) and B(2)R(-/-) mice. Hence, B(1)R and B(2)R deficiency are associated with increased oxidative stress, but there is a differential imbalance between free radical production and antioxidant defense. The interrelationship between the differential B(1)R and B(2)R roles in oxidative stress and cardiovascular diseases remain to be investigated. PMID:24020815

  6. CA2+-DEPENDENT AND CA2+-INDEPENDENT MECHANISM OF CYCLIC-AMP REDUCTION - MEDIATION BY BRADYKININ B-2 RECEPTORS

    NARCIS (Netherlands)

    SIPMA, H; DENHERTOG, A; NELEMANS, A

    1995-01-01

    1 Bradykinin caused a transient reduction of about 25% in the cyclic AMP level in forskolin prestimulated DDT1 MF-2 smooth muscle cells (IC50: 36.4 +/- 4.9 nM) and a pronounced, sustained inhibition (40%) of the isoprenaline-stimulated cyclic AMP level (IC50: 37.5 +/- 1.1 nM). 2 The Ca2+ ionophore,

  7. Antagonism of Bradykinin B2 Receptor Prevents Inflammatory Responses in Human Endothelial Cells by Quenching the NF-kB Pathway Activation

    Science.gov (United States)

    Terzuoli, Erika; Meini, Stefania; Cucchi, Paola; Catalani, Claudio; Cialdai, Cecilia; Maggi, Carlo Alberto; Giachetti, Antonio; Ziche, Marina; Donnini, Sandra

    2014-01-01

    Background Bradykinin (BK) induces angiogenesis by promoting vessel permeability, growth and remodeling. This study aimed to demonstrate that the B2R antagonist, fasitibant, inhibits the BK pro-angiogenic effects. Methodology We assesed the ability of fasibitant to antagonize the BK stimulation of cultured human cells (HUVEC) and circulating pro-angiogenic cells (PACs), in producing cell permeability (paracellular flux), migration and pseocapillary formation. The latter parameter was studied in vitro (matrigel assay) and in vivo in mice (matrigel plug) and in rat model of experimental osteoarthritis (OA). We also evaluated NF-κB activation in cultured cells by measuring its nuclear translocation and its downstream effectors such as the proangiogenic ciclooxygenase-2 (COX-2), prostaglandin E-2 and vascular endothelial growth factor (VEGF). Principal findings HUVEC, exposed to BK (1–10 µM), showed increased permeability, disassembly of adherens and tight-junction, increased cell migration, and pseudocapillaries formation. We observed a significant increase of vessel density in the matrigel assay in mice and in rats OA model. Importantly, B2R stimulation elicited, both in HUVEC and PACs, NF-κB activation, leading to COX-2 overexpression, enhanced prostaglandin E-2 production. and VEGF output. The BK/NF-κB axis, and the ensuing amplification of inflammatory/angiogenic responses were fully prevented by fasitibant as well as by IKK VII, an NF-κB. Inhibitor. Conclusion This work illustrates the role of the endothelium in the inflammation provoked by the BK/NF-κB axis. It also demonstates that B2R blockade by the antaogonist fasibitant, abolishes both the initial stimulus and its amplification, strongly attenuating the propagation of inflammation. PMID:24392129

  8. Effects of trout bradykinin on the motility of the trout stomach and intestine: evidence for a receptor distinct from mammalian B1 and B2 subtypes

    OpenAIRE

    Jensen, Jorgen; J. Michael Conlon

    1997-01-01

    Trout bradykinin ([Arg0,Trp5,Leu8]-bradykinin; trout BK), recently isolated from kallikrein-treated trout plasma, produced sustained and concentration-dependent contractions of isolated longitudinal muscle from rainbow trout stomach (pD2=7.01±0.03) and proximal small intestine (pD2=7.37±0.07). The maximum responses were 85±2% (stomach) and 101±35% (intestine) of the corresponding responses to 10−5 M acetylcholine. Strips of circular smooth muscle from trout stomach and intestine did not contr...

  9. Bradykinin and adenosine receptors mediate desflurane induced postconditioning in human myocardium: role of reactive oxygen species

    Directory of Open Access Journals (Sweden)

    Gérard Jean-Louis

    2010-07-01

    Full Text Available Abstract Background Desflurane during early reperfusion has been shown to postcondition human myocardium, in vitro. We investigated the role of adenosine and bradykinin receptors, and generation of radical oxygen species in desflurane-induced postconditioning in human myocardium. Methods We recorded isometric contraction of human right atrial trabeculae hanged in an oxygenated Tyrode's solution (34 degrees Celsius, stimulation frequency 1 Hz. After a 30-min hypoxic period, desflurane 6% was administered during the first 5 min of reoxygenation. Desflurane was administered alone or with pretreatment of N-mercaptopropionylglycine, a reactive oxygen species scavenger, 8-(p-Sulfophenyltheophylline, an adenosine receptor antagonist, HOE140, a selective B2 bradykinin receptor antagonist. In separate groups, adenosine and bradykinin were administered during the first minutes of reoxygenation alone or in presence of N-mercaptopropionylglycine. The force of contraction of trabeculae was recorded continuously. Developed force at the end of a 60-min reoxygenation period was compared (mean ± standard deviation between the groups by a variance analysis and post hoc test. Results Desflurane 6% (84 ± 6% of baseline enhanced the recovery of force after 60-min of reoxygenation as compared to control group (51 ± 8% of baseline, P N-mercaptopropionylglycine (54 ± 3% of baseline, 8-(p-Sulfophenyltheophylline (62 ± 9% of baseline, HOE140 (58 ± 6% of baseline abolished desflurane-induced postconditioning. Adenosine (80 ± 9% of baseline and bradykinin (83 ± 4% of baseline induced postconditioning (P vs control, N-mercaptopropionylglycine abolished the beneficial effects of adenosine and bradykinin (54 ± 8 and 58 ± 5% of baseline, respectively. Conclusions In vitro, desflurane-induced postconditioning depends on reactive oxygen species production, activation of adenosine and bradykinin B2 receptors. And, the cardioprotective effect of adenosine and bradykinin

  10. Study on the expression of bradykinin and its receptors B1R and B2R in the kidney immune injury in trichloroethylene-sensitized mouse%三氯乙烯致敏小鼠肾脏免疫损伤中缓激肽及其受体B1R和B2R的表达水平

    Institute of Scientific and Technical Information of China (English)

    王慧; 张家祥; 李树龙; 查晚生; 王峰; 朱启星

    2015-01-01

    Objective To study the expression of bradykinin and its receptors B1R and B2R in the kidney immune injury in trichloroethylene-sensitized mouse and discuss the pathogenesis of Dermatitis Medicamentosa-like of TCE (ODMLT).Methods On the first days,intradermal injection by 50% TCE and the amount of FCA mixture 100μl for initial sensitization;on 4,7,10 days,painted abdominal skin by 100 μl 50% TCE for three sensitization,on 17,19 days,painted on the back skin by 100 μl 30% TCE for initial excitation and the last challenge;24 h before each challenge,PKSI-527+TCE group received intraperitoneal injection by inhibitor PKSI-527 (50 mg/kg);solvent control group treat without TCE and sensitization and excitation reagent the same proportion of olive oil and acetone mixture,blank control group without any treatment.Before killing the mouse,renal weight and body weight were recorded.The renals and plasma were separated at 24 h,48 h,72 h and 7 d after the last challenge and observed pathological of the renals.Expression of B1R and B2R in renal were examined by immunofluorescence technique.Plasma were examined by ELISA for BK.Results The renal pathological examination revealed the apparent damage of TCE sensitized mice which compared to solvent control group showed obvious cellular infiltration,vacuolar degeneration of renal tubular epithelial cells.The renal damage of PKSI-527+TCE-sensitized groups which compared to the corresponding point of TCE-sensitized groups showed significantly reduced.The expression of BK in 24 h,48 h and 72 h TCE-sensitized groups were significant higher than solvent control group and related TCE non-sensitized groups (P<0.05) and 72 h point compared to the corresponding point of PKSI-527+TCE group was also increased,,the difference was statistically significant (P<0.05).The expression levels of B1R and B2R in the kidney in 24 h,48 h,72 h and 7 d TCE-sensitized groups were obviously higher than solvent control group and related TCE non

  11. Bradykinin Type 2 Receptor BE1 Genotype Influences Bradykinin-Dependent Vasodilation During Angiotensin-Converting Enzyme Inhibition

    OpenAIRE

    Van Guilder, Gary P.; Pretorius, Mias; Luther, James M.; Byrd, J. Brian; Hill, Kevin; Gainer, James V.; Brown, Nancy J.

    2008-01-01

    To test the hypothesis that the bradykinin receptor 2 (BDKRB2) BE1 +9/−9 polymorphism affects vascular responses to bradykinin, we measured the effect of intra-arterial bradykinin on forearm blood flow and tissue-type plasminogen activator (t-PA) release in 89 normotensive, nonsmoking, white American subjects in whom degradation of bradykinin was blocked by enalaprilat. BE1 genotype frequencies were +9/+9:+9/−9:−9/−9=19:42:28. BE1 genotype was associated with systolic blood pressure (121.4±2....

  12. Bradykinin as a pain mediator: receptors are localized to sensory neurons, and antagonists have analgesic actions

    International Nuclear Information System (INIS)

    Autoradiographic studies localize [3H]bradykinin receptor binding sites to the substantia gelatinosa, dorsal root, and a subset of small cells in both the dorsal root and trigeminal ganglia of the guinea pig. [3H]Bradykinin labeling is also observed over myocardinal/coronary visceral afferent fibers. The localization of [3H]bradykinin receptors to nociceptive pathways supports a role for bradykinin in pain mediation. Several bradkykinin antagonists block bradykinin-induced acute vascular pain in the rat. The bradykinin antagonists also relieve bradykinin- and urate-induced hyperalgesia in the rat paw. These results indicate that bradykinin is a physiologic mediator of pain and that bradykinin antagonists have analgesic activity in both acute and chronic pain models

  13. Bradykinin potentiation by angiotensin-(1-7) and ACE inhibitors correlates with ACE C- and N-domain blockade

    NARCIS (Netherlands)

    B. Tom (Beril); R. de Vries (René); P.R. Saxena (Pramod Ranjan); A.H.J. Danser (Jan)

    2001-01-01

    textabstractACE inhibitors block B(2) receptor desensitization, thereby potentiating bradykinin beyond blocking its hydrolysis. Angiotensin (Ang)-(1-7) also acts as an ACE inhibitor and, in addition, may stimulate bradykinin release via angiotensin II type 2 receptors.

  14. Bradykinin-induced proinflammatory signaling mechanisms.

    Science.gov (United States)

    Shigematsu, Sakuji; Ishida, Shuji; Gute, Dean C; Korthuis, Ronald J

    2002-12-01

    Intravital microscopic techniques were used to examine the mechanisms underlying bradykinin-induced leukocyte/endothelial cell adhesive interactions (LECA) and venular protein leakage (VPL) in single postcapillary venules of the rat mesentery. The effects of bradykinin superfusion to increase LECA and VPL were prevented by coincident topical application of either a bradykinin-B(2) receptor antagonist, a cell-permeant superoxide dismutase (SOD) mimetic or antioxidant, or inhibitors of cytochrome P-450 epoxygenase (CYPE) or protein kinase C (PKC) but not by concomitant treatment with either SOD, a mast cell stabilizer, or inhibitors of nitric oxide synthase, cyclooxygenase, xanthine oxidase, NADPH oxidase, or platelet-activating factor. Immunoneutralizing P-selectin or intercellular adhesion molecule-1 (ICAM-1) completely prevented bradykinin-induced leukocyte adhesion and emigration but did not affect VPL. On the other hand, stabilization of F-actin with phalloidin prevented bradykinin-induced leukocyte emigration and VPL but did not alter leukocyte adhesion. These data indicate that bradykinin induces LECA in rat mesenteric venules via a B(2)-receptor-initiated, CYPE-, oxidant- and PKC-mediated, P-selectin- and ICAM-1-dependent mechanism. Bradykinin also produced VPL, an effect that was initiated by stimulation of B(2) receptors and involved CYPE and PKC activation, oxidant generation, and cytoskeletal reorganization but was independent of leukocyte adherence and emigration. PMID:12388246

  15. Bradykinin-mediated angioedema.

    Science.gov (United States)

    Obtułowicz, Krystyna

    2016-02-01

    Angioedema and urticaria often constitute a challenge in daily clinical practice. They may either co- -occur or present as independent conditions. They are characterized by a complex pathomechanism, and their symptoms may be triggered by diverse factors. These differences are crucial for developing a successful treatment regimen. Both conditions may have an allergic origin (immunoglobulin [Ig] E and non-IgE-related), usually induced by histamine, or a nonallergic one, such as bradykinin-mediated angioedema in patients with C1 inhibitor (C1-INH) deficiency or angioedema induced by certain drugs (eg, angiotensin-converting enzyme inhibitors). Currently, we distinguish 5 types of nonallergic angioedema: hereditary angioedema (HAE) due to C1-INH deficiency, acquired angioedema (AAE), and angioedema induced by the renin-angiotensin-aldosterone system, all of which are mediated by bradykinin, as well as pseudoallergic angioedema and idiopathic angioedema. Bradykinin-mediated angioedema (eg, laryngeal angioedema) may be life-threatening because of resistance to corticosteroids and antihistamine drugs. C1-INH concentrates are the drugs of choice in the treatment of HAE and AAE. In recent years, some new drugs have been introduced in the treatment of bradykinin-mediated angioedema, such as bradykinin B2-receptor antagonist, icatibant, and kallikrein inhibitor, ecallantide, which allow to improve treatment outcomes. PMID:26842379

  16. Improvement of skin wound healing in diabetic mice by kinin B2 receptor blockade

    OpenAIRE

    Desposito, D.; Chollet, C.; Taveau, C.; Descamps, V.; Alhenc-Gelas, F.; Roussel, R.; Bouby, Nadine; Waeckel, L.

    2015-01-01

    Impaired skin wound healing is a major medical problem in diabetic subjects. Kinins exert a number of vascular and other actions limiting organ damage in ischaemia or diabetes, but their role in skin injury is unknown. We investigated, through pharmacological manipulation of bradykinin B1 and B2 receptors (B1R and B2R respectively), the role of kinins in wound healing in non-diabetic and diabetic mice. Using two mouse models of diabetes (streptozotocin-induced and db/db mice) and non-diabetic...

  17. Human umbilical vein: involvement of cyclooxygenase-2 pathway in bradykinin B1 receptor-sensitized responses.

    Science.gov (United States)

    Errasti, A E; Rey-Ares, V; Daray, F M; Rogines-Velo, M P; Sardi, S P; Paz, C; Podestá, E J; Rothlin, R P

    2001-08-01

    In isolated human umbilical vein (HUV), the contractile response to des-Arg9-bradykinin (des-Arg9-BK), selective BK B1 receptor agonist, increases as a function of the incubation time. Here, we evaluated whether cyclooxygenase (COX) pathway is involved in BK B1-sensitized response obtained in 5-h incubated HUV rings. The effect of different concentrations of indomethacin, sodium salicylate, ibuprofen, meloxicam, lysine clonixinate or NS-398 administrated 30 min before concentration-response curves (CRC) was studied. All treatments produced a significant rightward shift of the CRC to des-Arg9-BK in a concentration-dependent manner, which provides pharmacological evidence that COX pathway is involved in the BK B1 responses. Moreover, in this tissue, the NS-398 pKb (5.2) observed suggests that COX-2 pathway is the most relevant. The strong correlation between published pIC50 for COX-2 and the NSAIDs' pKbs estimated further supports the hypothesis that COX-2 metabolites are involved in BK B1 receptor-mediated responses. In other rings, indomethacin (30, 100 micromol/l) or NS-398 (10, 30 micromol/l) produced a significant rightward shift of the CRC to BK, selective BK B2 agonist, and its pKbs were similar to the values to inhibit BK B1 receptor responses, suggesting that COX-2 pathway also is involved in BK B2 receptor responses. Western blot analysis shows that COX-1 and COX-2 isoenzymes are present before and after 5-h in vitro incubation and apparently COX-2 does not suffer additional induction. PMID:11534854

  18. Up-regulation of bradykinin receptors in rat bronchi via I kappa B kinase-mediated inflammatory signaling pathway

    DEFF Research Database (Denmark)

    Lei, Ying; Zhang, Yaping; Cao, Yongxiao; Edvinsson, Lars; Xu, Cang-Bao

    IkappaB kinase (IKK)-mediated intracellular signaling mechanisms may be involved in airway hyperresponsiveness through up-regulation of bradykinin receptors. This study was designed to examine if organ culture of rat bronchial segments induces airway hyperresponsiveness to bradykinin and if inhib...

  19. Pathophysiology of a severe case of Puumala hantavirus infection successfully treated with bradykinin receptor antagonist icatibant.

    Science.gov (United States)

    Vaheri, Antti; Strandin, Tomas; Jääskeläinen, Anne J; Vapalahti, Olli; Jarva, Hanna; Lokki, Marja-Liisa; Antonen, Jaakko; Leppänen, Ilona; Mäkelä, Satu; Meri, Seppo; Mustonen, Jukka

    2014-11-01

    We recently described a patient with very severe Puumala hantavirus infection manifested by capillary leakage syndrome and shock. He was successfully treated with the bradykinin receptor antagonist, icatibant (Antonen et al., 2013). Here we report analysis of the pathophysiology which indicated pronounced complement activation, prolonged leukocytosis, extensive fibrinolysis, circulating histones, and defects in liver function. The patient had an uncommon HLA-phenotype, which may have contributed to the severe course of the disease. PMID:25194993

  20. Bradykinin-mediated diseases.

    Science.gov (United States)

    Kaplan, Allen P

    2014-01-01

    Diseases which have been demonstrated to be caused by increased plasma levels of bradykinin all have angioedema as the common major clinical manifestation. Angioedema due to therapy with angiotensin-converting enzyme (ACE) inhibitors is caused by suppressed bradykinin degradation so that it accumulates. This occurs because ACE metabolizes bradykinin by removal of Phe-Arg from the C-terminus, which inactivates it. By contrast, angioedema due to C1 inhibitor deficiency (either hereditary types I and II, or acquired) is caused by bradykinin overproduction. C1 inhibitor inhibits factor XIIa, kallikrein and activity associated with the prekallikrein-HK (high-molecular-weight kininogen) complex. In its absence, uncontrolled activation of the plasma bradykinin cascade is seen once there has been an initiating stimulus. C4 levels are low in all types of C1 inhibitor deficiency due to the instability of C1 (C1r, in particular) such that some activated C1 always circulates and depletes C4. In the hereditary disorder, formation of factor XIIf (factor XII fragment) during attacks of swelling causes C4 levels to drop toward zero, and C2 levels decline. A kinin-like molecule, once thought to be a cleavage product derived from C2 that contributes to the increased vascular permeability seen in hereditary angioedema (HAE), is now thought to be an artifact, i.e. no such molecule is demonstrable. The acquired C1 inhibitor deficiency is associated with clonal disorders of B cell hyperreactivity, including lymphoma and monoclonal gammopathy. Most cases have an IgG autoantibody to C1 inhibitor which inactivates it so that the presentation is strikingly similar to type I HAE. New therapies for types I and II HAE include C1 inhibitor replacement therapy, ecallantide, a kallikrein antagonist, and icatibant, a B2 receptor antagonist. A newly described type III HAE has normal C1 inhibitor, although it is thought to be mediated by bradykinin, as is an antihistamine-resistant subpopulation of

  1. Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition.

    Science.gov (United States)

    Chuang, H H; Prescott, E D; Kong, H; Shields, S; Jordt, S E; Basbaum, A I; Chao, M V; Julius, D

    2001-06-21

    Tissue injury generates endogenous factors that heighten our sense of pain by increasing the response of sensory nerve endings to noxious stimuli. Bradykinin and nerve growth factor (NGF) are two such pro-algesic agents that activate G-protein-coupled (BK2) and tyrosine kinase (TrkA) receptors, respectively, to stimulate phospholipase C (PLC) signalling pathways in primary afferent neurons. How these actions produce sensitization to physical or chemical stimuli has not been elucidated at the molecular level. Here, we show that bradykinin- or NGF-mediated potentiation of thermal sensitivity in vivo requires expression of VR1, a heat-activated ion channel on sensory neurons. Diminution of plasma membrane phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) levels through antibody sequestration or PLC-mediated hydrolysis mimics the potentiating effects of bradykinin or NGF at the cellular level. Moreover, recruitment of PLC-gamma to TrkA is essential for NGF-mediated potentiation of channel activity, and biochemical studies suggest that VR1 associates with this complex. These studies delineate a biochemical mechanism through which bradykinin and NGF produce hypersensitivity and might explain how the activation of PLC signalling systems regulates other members of the TRP channel family. PMID:11418861

  2. New Aspects of Ace Inhibition: Importance of ACE co-localization with angiotensin and bradykinin receptors

    NARCIS (Netherlands)

    B. Tom (Beril)

    2003-01-01

    textabstractThe beneficial effect of angiotensin-converting enzyme (ACE) inhibitors in hypertension and heart failure may relate, at least in part, to their capacity to interfere with bradykinin metabolism. In addition, recent studies have provided evidence for bradykinin-potentiating effects of ACE

  3. Bradykinin type 2 receptor -9/-9 genotype is associated with triceps brachii muscle hypertrophy following strength training in young healthy men

    Directory of Open Access Journals (Sweden)

    Popadic Gacesa Jelena Z

    2012-11-01

    Full Text Available Abstract Background Bradykinin type 2 receptor (B2BRK genotype was reported to be associated with changes in the left-ventricular mass as a response to aerobic training, as well as in the regulation of the skeletal muscle performance in both athletes and non-athletes. However, there are no reports on the effect of B2BRK 9-bp polymorphism on the response of the skeletal muscle to strength training, and our aim was to determine the relationship between the B2BRK SNP and triceps brachii functional and morphological adaptation to programmed physical activity in young adults. Methods In this 6-week pretest-posttest exercise intervention study, twenty nine healthy young men (21.5 ± 2.7 y, BMI 24.2 ± 3.5 kg/m2 were put on a 6-week exercise protocol using an isoacceleration dynamometer (5 times a week, 5 daily sets with 10 maximal elbow extensions, 1 minute rest between sets. Triceps brachii muscle volumes were assessed by using magnetic resonance imaging before and after the strength training. Bradykinin type 2 receptor 9 base pair polymorphism was determined for all participants. Results Following the elbow extensors training, an average increase in the volume of both triceps brachii was 5.4 ± 3.4% (from 929.5 ± 146.8 cm3 pre-training to 977.6 ± 140.9 cm3 after training, p9 allele compared to individuals with one or two +9 alleles (−9/-9, 8.5 ± 3.8%; vs. -9/+9 and +9/+9 combined, 4.7 ± 4.5%, p B2BRK genotype (−9/-9, 50.2 ± 19.2%; vs. -9/+9 and +9/+9 combined, 46.8 ± 20.7%, p > 0.05. Conclusions We found that muscle morphological response to targeted training – hypertrophy – is related to polymorphisms of B2BRK. However, no significant influence of different B2BRK genotypes on functional muscle properties after strength training in young healthy non athletes was found. This finding could be relevant, not only in predicting individual muscle adaptation capacity to training or sarcopenia related to aging and inactivity, but also in

  4. The bradykinin BK2 receptor mediates angiotensin II receptor type 2 stimulated rat duodenal mucosal alkaline secretion

    Directory of Open Access Journals (Sweden)

    Helander Herbert F

    2003-02-01

    Full Text Available Abstract Background This study investigates bradykinin and nitric oxide as potential mediators of AT2-receptor-stimulated duodenal mucosal alkaline secretion. Duodenal mucosal alkaline secretion was measured in methohexital- and α-chloralose-anaesthetised rats by means of in situ pH-stat titration. Immunohistochemistry and Western blot were used to identify the BK2 receptors. Results The AT2 receptor agonist CGP42112A (0.1 μg kg-1 min-1 administered intravenously increased the duodenal mucosal alkaline secretion by ~50 %. This increase was sensitive to the selective BK2 receptor blocker HOE140 (100 ng/kg iv, but not to luminal administration of the NOS blocker L-NAME (0.3 mM. Mean arterial pressure did not differ between groups during the procedures. Immunohistochemistry showed a distinct staining of the crypt epithelium and a moderate staining of basal cytoplasm in villus enterocytes. Conclusion The results suggest that the AT2-receptor-stimulated alkaline secretion is mediated via BK2 receptors located in the duodenal cryptal mucosal epithelium.

  5. Bradykinin activation of extracellular signal-regulated kinases in human trabecular meshwork cells

    OpenAIRE

    Webb, Jerry G.; Yang, Xiaofeng; Crosson, Craig E.

    2011-01-01

    Bradykinin stimulation of B2 kinin receptors has been shown to promote matrix metalloproteinase (MMP) secretion from trabecular meshwork cells and to increase conventional outflow facility. Because acute secretion of MMPs can be dependent on the activity of extracellular signal-regulated MAP kinases (ERK1/2), experiments were performed to determine bradykinin effects on ERK1/2 in cultured human trabecular meshwork cells and the relationship of these effects to MMP-9 release. Treatment of cell...

  6. Expression of HER2 and bradykinin B1 receptors in precursor lesions of gallbladder carcinoma

    Institute of Scientific and Technical Information of China (English)

    Cesar Toledo; Carola E Matus; Ximena Barraza; Pamela Arroyo; Pamela Ehrenfeld; Carlos D Figueroa; Kanti D Bhoola; Maeva del Pozo; Maria T Poblete

    2012-01-01

    AIM:TO determine the expression of HER2 and bradykinin B1 receptors (B1R) in the two pathogenic models of gallbladder cancer:the metaplasia-dysplasia-carcinoma and the adenoma-carcinoma pathways.METHODS:Receptor proteins were visualized by immunohistochemistry on 5-μm sections of paraffin-embedded tissue.Expression of both receptors was studied in biopsy samples from 92 patients (6 males and 86 females; age ranging from 28 to 86 years,mean 56 years).High HER2 expression in specimens was additionally investigated by fluorescence in situ hybridization.Cell proliferation in each sample was assessed by using the Ki-67 proliferation marker.RESULTS:HER2 receptor protein was absent in adenomas and in normal gallbladder epithelium.On the contrary,there was intense staining for HER2 on the basolateral membrane of epithelial cells of intestinal metaplasia (22/24; 91.7%) and carcinoma in situ (9/10;90%),the lesions that displayed a significantly high proliferation index.Protein up-regulation of HER2 in the epithelium with metaplasia or carcinoma in situ was not accompanied by HER2 gene amplification.A similar result was observed in invasive carcinomas (0/12).The B1R distribution pattern mirrored that of HER2 except that B1R was additionally observed in the adenomas.The B1R appeared either as cytoplasmic dots or labelingon the apical cell membrane of the cells composing the epithelia with intestinal metaplasia (24/24; 100%) and carcinoma in situ (10/10; 100%) and in the epithelial cells of adenomas.In contrast,both HER2 (4/12; 33%)and B1R (1/12; 8.3%) showed a low expression in invasive gallbladder carcinomas.CONCLUSION:The up-regulation of HER2 and B1R in precursor lesions of gallbladder carcinoma suggests cross-talk between these two receptors that may be of importance in the modulation of cell proliferation in gallbladder carcinogenesis.

  7. The role of N-terminal and C-terminal Arg residues from BK on interaction with kinin B2 receptor.

    Science.gov (United States)

    Filippelli-Silva, Rafael; Martin, Renan P; Rodrigues, Eliete S; Nakaie, Clovis R; Oliveira, Laerte; Pesquero, João B; Shimuta, Suma I

    2016-04-01

    Bradykinin (BK) is a nonapeptide important for several physiological processes such as vasodilatation, increase in vascular permeability and release of inflammatory mediators. BK performs its actions by coupling to and activating the B2 receptor, a family A G-protein coupled receptor. Using a strategy which allows systematical monitoring of BK R1 and R9 residues and B2 receptor acidic residues Glu5.35(226) and Asp6.58(298), our study aims at clarifying the BK interaction profile with the B2 receptor [receptor residue numbers are normalized according to Ballesteros and Weinstein, Methods Neurosci. 25 (1995), pp. 366-428) followed by receptor sequence numbering in brackets]. N- and C-terminal analogs of BK (-A1, -G1, -K1, -E1 and BK-A9) were tested against wild type B2, Glu5.35(226)Ala and Asp6.58(298)Ala B2 mutant receptors for their affinity and capability to elicit responses by mechanical recordings of isolated mice stomach fundus, measuring intracellular calcium mobilization, and competitive fluorimetric binding assays. BK showed 2- and 15-fold decreased potency for Glu5.35(226) and Asp6.58(298) B2 mutant receptors, respectively. In B2-Glu5.35(226)Ala BK analogs showed milder reduction in evaluated parameters. On the other hand, in the B2-Asp6.58(298)Ala mutant, no N-terminal analog was able to elicit any response. However, the BK-A9 analog presented higher affinity parameters than BK in the latter mutant. These findings provide enough support for defining a novel interaction role of BK-R9 and Asp6.58(298) receptor residues. PMID:26584354

  8. [Bradykinin mediated angioedema].

    Science.gov (United States)

    Bouillet, L; Boccon-Gibod, I; Massot, C

    2011-04-01

    Bradykinin angioedema (AE) are characterized by acute recurrent episodes of localized swelling. They are not associated with pruritus or erythema, and are short-lived (24 to 72 hours), disappearing without any sequelae. Corticosteroids are useless. Skin or mucous membranes (upper respiratory and intestinal) could be affected. Bradykinin AE can be secondary to: (1) AE associated with C1 inhibitor deficiency (hereditary or acquired); (2) drug-induced AE (converting enzyme inhibitors…); (3) type III AE type (oestrogen dependant) without C1 inhibitor deficiency. These type III AE can be associated with a gain of function mutation that markedly increases factor XII activity. Prognosis depends on the laryngeal attacks (resulting in 25 % of death in the absence of specific treatment). In case of severe attacks, icatibant (bradykinin receptor antagonist) or C1 inhibitor concentrate can be used. In case of frequent attacks, long-term therapy with danazol or tranexamic acid is effective. PMID:20538389

  9. NMR and computational evidence that high-affinity bradykinin receptor antagonists adopt C-terminal beta-turns.

    Science.gov (United States)

    Kyle, D J; Blake, P R; Smithwick, D; Green, L M; Martin, J A; Sinsko, J A; Summers, M F

    1993-05-14

    Three tetrapeptides were prepared, each corresponding to the four C-terminal amino acid residues of highly potent, second-generation bradykinin receptor antagonists. The tetrapeptides are (IA) Ser-D-Phe-Oic-Arg, (IIA) Ser-D-Tic-Oic-Arg, and (IIIA) Ser-D-Hype(trans-propyl)-Oic-Arg. Solution conformations for each were determined by incorporating interproton distance restraints, determined by 2D NMR experiments performed in water at neutral pH, into a series of distance geometry/simulated annealing model building calculations. Similarly, systematic conformational analyses were performed for each using molecular mechanics calculations. Both the NMR-derived structures, as well as the calculated structures, are shown to adopt a beta-turn as the primary conformation. Excellent agreement between the predicted structures and the NMR-derived structures is demonstrated. Aside from being the first examples of linear tetrapeptides reported to be ordered in aqueous solvent, the results presented support the hypothesis that high-affinity bradykinin receptor antagonists must adopt C-terminal beta-turn conformations. PMID:8388469

  10. Expression of the ephrin receptor B2 in the embryonic chicken bursa of Fabricius

    Science.gov (United States)

    Chicken B-cells develop in a specific organ, the bursa of Fabricius. To understand the bursal microenvironment guiding B-cell development, previous studies identified ephrin (Eph) receptor B2 (EphB2) gene transcripts in the embryonic bursa. We hypothesize that the EphB2 receptors and their ligands r...

  11. Regulation of cyclic AMP response-element binding-protein (CREB) by Gq/11-protein-coupled receptors in human SH-SY5Y neuroblastoma cells

    OpenAIRE

    Rosethorne, Elizabeth M; Nahorski, Stefan R; Challiss, R.A. John

    2008-01-01

    Human SH-SY5Y neuroblastoma cells have been used to investigate mechanisms involved in CREB phosphorylation after activation of two endogenously expressed Gq/11-protein-coupled receptors, the M3 muscarinic acetylcholine (mACh) and B2 bradykinin receptors. Stimulation with either methacholine or bradykinin resulted in maximal increases in CREB phosphorylation within 1 min, with either a rapid subsequent decrease (bradykinin) to basal levels, or a sustained response (methacholine). Inhibitor st...

  12. Bradykinin, ch. 26

    International Nuclear Information System (INIS)

    A radioimmunoassay for bradykinin is described. Methods of obtaining and processing blood and synovial fluid and subsequent isolation of bradykinin are given. To prepare the bradykinin immunogen, bradykinin is coupled to ovalbumin, using toluene diisocyanate. In order to determine the extent of coupling , ) 714C{-2,3 pro-bradykinin is used. Tyr8-bradykinin is iodinated with 125I by a modification of the Hunter-greenwood method. The iodination mixture is purified by an anion exchanger. Bound and free hormones are separated by dextran-coated charcoal. The sensitivity of the method is about 0.1 ng/ml. )

  13. ErbB2 resembles an autoinhibited invertebrate epidermal growth factor receptor

    Energy Technology Data Exchange (ETDEWEB)

    Alvarado, Diego; Klein, Daryl E.; Lemmon, Mark A.; (UPENN-MED)

    2009-09-25

    The orphan receptor tyrosine kinase ErbB2 (also known as HER2 or Neu) transforms cells when overexpressed, and it is an important therapeutic target in human cancer. Structural studies have suggested that the oncogenic (and ligand-independent) signalling properties of ErbB2 result from the absence of a key intramolecular 'tether' in the extracellular region that autoinhibits other human ErbB receptors, including the epidermal growth factor (EGF) receptor. Although ErbB2 is unique among the four human ErbB receptors, here we show that it is the closest structural relative of the single EGF receptor family member in Drosophila melanogaster (dEGFR). Genetic and biochemical data show that dEGFR is tightly regulated by growth factor ligands, yet a crystal structure shows that it, too, lacks the intramolecular tether seen in human EGFR, ErbB3 and ErbB4. Instead, a distinct set of autoinhibitory interdomain interactions hold unliganded dEGFR in an inactive state. All of these interactions are maintained (and even extended) in ErbB2, arguing against the suggestion that ErbB2 lacks autoinhibition. We therefore suggest that normal and pathogenic ErbB2 signalling may be regulated by ligands in the same way as dEGFR. Our findings have important implications for ErbB2 regulation in human cancer, and for developing therapeutic approaches that target novel aspects of this orphan receptor.

  14. In vitro and in vivo activity of analogues of the kinin B2 receptor antagonist MEN1 1270.

    Science.gov (United States)

    Meini, S; Lecci, A; Carini, F; Tramontana, M; Giuliani, S; Maggi, C A; Ricci, R; Fabbri, G; Anichini, B; Harmat, N; Rizzi, A; Camarda, V; Regoli, D; Quartara, L

    2002-04-01

    In this study, we describe the in vitro and in vivo activities of a series of cyclic peptide analogues of the selective kinin B2 receptor antagonist MEN11270 on Chinese hamster ovary cells expressing the human B2 receptor (hB2R), the human isolated umbilical vein (hUV), the isolated guinea pig ileum (gpI), and bradykinin (BK) induced bronchoconstriction (BC) and hypotension in anaesthetized guinea pigs. Substitutions in the backbone of MEN1 1270 (H-DArg-Arg-Pro-Hyp-Gly-Thi-c(Dab-DTic-Oic-Arg)c(7gamma-10alpha)) aimed to increase the potency in inhibiting bronchospasm versus hypotension following the topical (intratracheal (i.t.)) or systemic (intravenous (i.v.)) application of these antagonists. A series of analogues were left unprotected from N-terminal cleavage by aminopeptidases (MEN12739, MEN13052, MEN13346, and MEN13371): these compounds maintained sizeable affinities for the hB2R (pKi = 9.4, 9.6, 9.7, and 8.6, respectively) and antagonist activities toward BK in the hUV (pA2 = 7.9, 8.3, 8.2, and 7.5) and gpI assays (pK(B) = 7.4, 7.8, 7.9, and 7.9), but the inhibition of BK-induced BC and hypotension in vivo was negligible following either i.v. or i.t. administration. Two analogues (MEN12388 and MEN13405) could be potential substrates of angiotensin-converting enzyme: these have good activity in the hB2R (pKi = 9.5 and 8.9, respectively), hUV (pA2 = 8.2 for MEN12388), and gpI assays (pK(B) = 8.4 and 8.0) but an in vivo activity 10- to 30-fold lower than the parent compound MEN1 1270 (pKi = 9.4, pA2 = 8.1, pKB = 8.3) when given by either the i.v. or the i.t. route. Other analogues were functionalized with a quaternary ammonium Lys derivative (MEN13031, MEN12374, and the previously mentioned MEN13052) or with an ethyl group on Arg (MEN13655 and the previously mentioned MEN13346 and MEN13405) in order to hinder or facilitate local absorption. MEN13346 and MEN13031 (pKi = 9.7and 9.5, pA2 = 8.2 and 7.9, pKB = 7.9 and 8.5, respectively) were 10- to 30-fold less

  15. Activation of the human keratinocyte B1 bradykinin receptor induces expression and secretion of metalloproteases 2 and 9 by transactivation of epidermal growth factor receptor.

    Science.gov (United States)

    Matus, Carola E; Ehrenfeld, Pamela; Pavicic, Francisca; González, Carlos B; Concha, Miguel; Bhoola, Kanti D; Burgos, Rafael A; Figueroa, Carlos D

    2016-09-01

    The B1 bradykinin receptor (BDKRB1) is a component of the kinin cascade localized in the human skin. Some of the effects produced by stimulation of BDKRB1 depend on transactivation of epidermal growth factor receptor (EGFR), but the mechanisms involved in this process have not been clarified yet. The primary purpose of this study was to determine the effect of a BDKRB1 agonist on wound healing in a mouse model and the migration and secretion of metalloproteases 2 and 9 from human HaCaT keratinocytes and delineate the signalling pathways that triggered their secretion. Although stimulation of BDKRB1 induces weak chemotactic migration of keratinocytes and wound closure in an in vitro scratch-wound assay, the BDKRB1 agonist improved wound closure in a mouse model. BDKRB1 stimulation triggers synthesis and secretion of both metalloproteases, effects that depend on the activity of EGFR and subsequent phosphorylation of ERK1/2 and p38 mitogen-activated protein kinases and PI3K/Akt. In the mouse model, immunoreactivity for both gelatinases was concentrated around wound borders. EGFR transactivation by BDKRB1 agonist involves Src kinases family and ADAM17. In addition to extracellular matrix degradation, metalloproteases 2 and 9 regulate cell migration and differentiation, cell functions that are associated with the role of BDKRB1 in keratinocyte differentiation. Considering that BDKRB1 is up-regulated by inflammation and/or by cytokines that are abundant in the inflammatory milieu, more stable BDKRB1 agonists may be of therapeutic value to modulate wound healing. PMID:27093919

  16. HER2/ErbB2 Receptor Signaling in Rat and Human Prolactinoma Cells: Strategy for Targeted Prolactinoma Therapy

    OpenAIRE

    Fukuoka, Hidenori; Cooper, Odelia; MIZUTANI, JUN; Tong, Yunguang; Ren, Song-Guang; Bannykh, Serguei; Melmed, Shlomo

    2010-01-01

    Dopamine agonist resistance or intolerance is encountered in approximately 20% of prolactinoma patients. Because human epidermal growth factor receptor 2 (HER2)/ErbB2 is overexpressed in prolactinomas and ErbB receptor ligands regulate prolactin (PRL) gene expression, we tested the role of HER2/ErbB2 in prolactinoma hormone regulation and adenoma cell proliferation to assess the rationale for targeting this receptor for prolactinoma therapy. As we showed prolactinoma HER2 overexpression, we g...

  17. CPG2 Recruits Endophilin B2 to the Cytoskeleton for Activity-Dependent Endocytosis of Synaptic Glutamate Receptors.

    Science.gov (United States)

    Loebrich, Sven; Benoit, Marc Robert; Konopka, Jaclyn Aleksandra; Cottrell, Jeffrey Richard; Gibson, Joanne; Nedivi, Elly

    2016-02-01

    Internalization of glutamate receptors at the postsynaptic membrane via clathrin-mediated endocytosis (CME) is a key mechanism for regulating synaptic strength. A role for the F-actin cytoskeleton in CME is well established, and recently, PKA-dependent association of candidate plasticity gene 2 (CPG2) with the spine-cytoskeleton has been shown to mediate synaptic glutamate receptor internalization. Yet, how the endocytic machinery is physically coupled to the actin cytoskeleton to facilitate glutamate receptor internalization has not been demonstrated. Moreover, there has been no distinction of endocytic-machinery components that are specific to activity-dependent versus constitutive glutamate receptor internalization. Here, we show that CPG2, through a direct physical interaction, recruits endophilin B2 (EndoB2) to F-actin, thus anchoring the endocytic machinery to the spine cytoskeleton and facilitating glutamate receptor internalization. Regulation of CPG2 binding to the actin cytoskeleton by protein kinase A directly impacts recruitment of EndoB2 and clathrin. Specific disruption of EndoB2 or the CPG2-EndoB2 interaction impairs activity-dependent, but not constitutive, internalization of both NMDA- and AMPA-type glutamate receptors. These results demonstrate that, through direct interactions with F-actin and EndoB2, CPG2 physically bridges the spine cytoskeleton and the endocytic machinery, and this tripartite association is critical specifically for activity-dependent CME of synaptic glutamate receptors. PMID:26776730

  18. Structure of the ligand-binding domain of the EphB2 receptor at 2 Å resolution

    International Nuclear Information System (INIS)

    The crystal structure of the ligand-binding domain of a receptor tyrosine kinase EphB2, an important mediator of cell-cell communication, has been determined at a resolution of 2 Å. The structure confirms the induced-fit mechanism for the binding of ligands to EphB receptors. Eph tyrosine kinase receptors, the largest group of receptor tyrosine kinases, and their ephrin ligands are important mediators of cell–cell communication regulating cell attachment, shape and mobility. Recently, several Eph receptors and ephrins have also been found to play important roles in the progression of cancer. Structural and biophysical studies have established detailed information on the binding and recognition of Eph receptors and ephrins. The initial high-affinity binding of Eph receptors to ephrin occurs through the penetration of an extended G–H loop of the ligand into a hydrophobic channel on the surface of the receptor. Consequently, the G–H loop-binding channel of Eph receptors is the main target in the search for Eph antagonists that could be used in the development of anticancer drugs and several peptides have been shown to specifically bind Eph receptors and compete with the cognate ephrin ligands. However, the molecular details of the conformational changes upon Eph/ephrin binding have remained speculative, since two of the loops were unstructured in the original model of the free EphB2 structure and their conformational changes upon ligand binding could consequently not be analyzed in detail. In this study, the X-ray structure of unbound EphB2 is reported at a considerably higher 2 Å resolution, the conformational changes that the important receptor loops undergo upon ligand binding are described and the consequences that these findings have for the development of Eph antagonists are discussed

  19. Pharmacological characterisation of arthritis induced by Bothrops jararaca venom in rabbits: a positive cross talk between bradykinin, nitric oxide and prostaglandin E2.

    OpenAIRE

    Suzana B. V. Mello; Maria Luiza Guzzo; Luiz Filipe Santiago Lisboa; Farsky, Sandra H P

    2002-01-01

    BACKGROUND: Our previous results showed that nitric oxide (NO) and bradykinin (BK) mediate the arthritis induced by Bothrops jararaca venom (BjV) in rabbits. In this study, we investigated the contribution of each receptor of BK as well as the inter-relationship between NO and eicosanoids in BjV-induced arthritis. METHODS: The arthritis was induced in rabbits with 16 microg of BjV injected intra-articularly. Prostaglandin E2 (PGE2), thromboxane B2 (TxB2), leukotriene B4 (LTB4) (radioimmunoass...

  20. Synthetic phosphopeptide immunogens yield activation-specific antibodies to the c-erbB-2 receptor.

    OpenAIRE

    Epstein, R. J.; Druker, B J; T. M. Roberts; Stiles, C D

    1992-01-01

    We inoculated rabbits with synthetic phosphopeptides, duplicating a major autophosphorylation site of the c-erbB-2 protooncogene product. The rabbits produced antisera that, after reverse immunoaffinity purification, selectively recognize the erbB-2 protein in its enzymatically active configuration. These anti-phosphopeptide antisera identify a subset of erbB-2-positive human cell lines wherein the protein is constitutively active as a tyrosine kinase. Synthetic phosphopeptides incorporating ...

  1. Identification and functional analysis of a novel bradykinin inhibitory peptide in the venoms of New World Crotalinae pit vipers

    International Nuclear Information System (INIS)

    A novel undecapeptide has been isolated and structurally characterized from the venoms of three species of New World pit vipers from the subfamily, Crotalinae. These include the Mexican moccasin (Agkistrodon bilineatus), the prairie rattlesnake (Crotalus viridis viridis), and the South American bushmaster (Lachesis muta). The peptide was purified from all three venoms using a combination of gel permeation chromatography and reverse-phase HPLC. Automated Edman degradation sequencing and MALDI-TOF mass spectrometry established its peptide primary structure as: Thr-Pro-Pro-Ala-Gly-Pro-Asp-Val-Gly-Pro-Arg-OH, with a non-protonated molecular mass of 1063.18 Da. A synthetic replicate of the peptide was found to be an antagonist of bradykinin action at the rat vascular B2 receptor. This is the first bradykinin inhibitory peptide isolated from snake venom. Database searching revealed the peptide to be highly structurally related (10/11 residues) with a domain residing between the bradykinin-potentiating peptide and C-type natriuretic peptide domains of a recently cloned precursor from tropical rattlesnake (Crotalus durissus terrificus) venom gland. BIP thus represents a novel biological entity from snake venom

  2. Identification and functional analysis of a novel bradykinin inhibitory peptide in the venoms of New World Crotalinae pit vipers.

    Science.gov (United States)

    Graham, Robert Leslie James; Graham, Ciaren; McClean, Stephen; Chen, Tianbao; O'Rourke, Martin; Hirst, David; Theakston, David; Shaw, Chris

    2005-12-23

    A novel undecapeptide has been isolated and structurally characterized from the venoms of three species of New World pit vipers from the subfamily, Crotalinae. These include the Mexican moccasin (Agkistrodon bilineatus), the prairie rattlesnake (Crotalus viridis viridis), and the South American bushmaster (Lachesis muta). The peptide was purified from all three venoms using a combination of gel permeation chromatography and reverse-phase HPLC. Automated Edman degradation sequencing and MALDI-TOF mass spectrometry established its peptide primary structure as: Thr-Pro-Pro-Ala-Gly-Pro-Asp-Val-Gly-Pro-Arg-OH, with a non-protonated molecular mass of 1063.18 Da. A synthetic replicate of the peptide was found to be an antagonist of bradykinin action at the rat vascular B2 receptor. This is the first bradykinin inhibitory peptide isolated from snake venom. Database searching revealed the peptide to be highly structurally related (10/11 residues) with a domain residing between the bradykinin-potentiating peptide and C-type natriuretic peptide domains of a recently cloned precursor from tropical rattlesnake (Crotalus durissus terrificus) venom gland. BIP thus represents a novel biological entity from snake venom. PMID:16277978

  3. Truncated ErbB2 receptor enhances ErbB1 signaling and induces reversible, ERK-independent loss of epithelial morphology

    DEFF Research Database (Denmark)

    Egeblad, M; Mortensen, Ole Hartvig; Jäättelä, M

    2001-01-01

    Shedding of the extracellular domain of the ErbB2 tyrosine kinase receptor and expression of the remaining NH(2)-terminally truncated ErbB2 correlates with lymph node metastases and adverse outcome in human breast cancer. To study the possible signaling from such a truncated receptor, MCF-7 human...... breast cancer cells expressing NH(2)-terminally truncated ErbB2 (DeltaNErbB2) were compared with cells overexpressing wild-type ErbB2. Expression of DeltaNErbB2 in MCF-7 cells resulted in sustained activation of extracellular signal-regulated kinases (ERK) 1/2, extensive loss of the epithelial morphology....... In conclusion, constitutive signaling upon expression of the truncated ErbB2 receptor in human breast cancer cells promotes morphological changes indicative of a more motile and aggressive phenotype....

  4. Pharmacological characterization of homobaclofen on wild type and mutant GABA(B)1b receptors coexpressed with the GABA(B)2 receptor

    DEFF Research Database (Denmark)

    Jensen, Anders A.; Madsen, Bo E.; Krogsgaard-Larsen, P;

    2001-01-01

    Homobaclofen (5-amino-3-(4-chlorophenyl) pentanoic acid) is a homologue of the classical GABA(B) receptor agonist baclofen. In a recent study, the two enantiomers of this compound were tested in a GABA(B) receptor selective [3H]gamma-aminobutyric acid ([3H]GABA) binding assay using rat brain...... rat GABA(B)1b receptors coexpressed with rat GABA(B)2 receptors. The results from this study correlate nicely with the binding data from rat brain. (R)-Homobaclofen was shown to act like (R)-baclofen albeit with 20-fold less potency, and (S)-homobaclofen was inactive on the receptor. The discrepancies...... between the data obtained in this study and those from the guinea pig ileum model could be ascribed to differences in amino acid sequence or receptor splicing of GABA(B) receptors between the two species. Another explanation for the observation is the possible existence of a novel yet uncloned GABA...

  5. [Bradykinin-induced angioedema: Definition, pathogenesis, clinical presentation, diagnosis and therapy].

    Science.gov (United States)

    Hahn, J; Bas, M; Hoffmann, T K; Greve, J

    2015-12-01

    The incidence of bradykinin-induced angioedema is considerably lower than that of histamine-induced forms; however, the same is true for the clinician's knowledge of this condition. Bradykinin-induced angioedemas include hereditary angioedema (HAE), as well as acquired forms induced by drugs or antibody formation, e.g., during the course of oncologic disease. Drug-induced forms affect almost exclusively the head and neck region, and are thus important for the otorhinolaryngologist. Clear differentiation between histamine-induced angioedema (e. g., connected to allergy/urticaria) and bradykinin-induced angioedema is essential for selection of the specific treatment and may be lifesaving. Antihistamines and cortisone derivatives have no relevant effect in bradykinin induced-angioedema, whereas blood-derived C1 esterase inhibitor and bradykinin receptor 2 antagonists represent effective therapeutic options--both for acute and prophylactic treatment. PMID:26597136

  6. Development of the correlation study between mammographic appearances and expression of estrogen receptor, progesterone receptor and C-erbB-2 in patients with breast cancer

    International Nuclear Information System (INIS)

    Breast cancer is one of the most common female malignant tumors. The occurrence and development of breast cancer are often accompanied by abnormal gene expression. It has been well accepted that estrogen receptor (ER), progesterone receptor (PR) and C-erbB-2 (epidermal growth factor receptor-2) are the main reference indexes for clinical endocrine therapy and prognosis prediction. Oncogene expression reflects the malignant biological behavior of breast cancer from different perspectives. Those aggressive behaviors cause a variety of changes in histopathology and thus in imaging. Therefore, the imaging features of breast cancer may indirectly demonstrate the status of ER, PR and C-erbB-2 to a certain extent. Until now, because of its simple operation,low cost and high accuracy, mammography is still the preferred method in breast cancer screening and diagnosis, and has been proposed as a noninvasive technique for prediction of the expression of ER, PR and C-erbB-2. It has potential clinical value in preoperative assessment and non-surgical treatment for those who are not able to perform immunohistochemistry. This review summarized previous related studies and explored mammography as a noninvasive predictor for ER, PR and C-erbB-2. (authors)

  7. Cross-talk between Bradykinin and Epidermal Growth Factor in Regulating IL-6 Production in Human Airway Smooth Muscle Cells

    Directory of Open Access Journals (Sweden)

    Po-Hao Feng

    2010-02-01

    Full Text Available Background: Bradykinin (BK, a G-protein-coupled-receptor (GPCR agonist via the B2receptor induces interleukin (IL-6 expression in airway smooth muscle(ASM cells by involving the extracellular signal-regulated kinase 1/2(ERK1/2 signaling pathway. In some cell species, GPCR agonists have beenshown to activate the ERK 1/2 pathway via transactivation of epidermalgrowth factor (EGF receptor (EGFR. In this study, we tested whether thereis cross-talk between BK and EGF in the regulation of IL-6 gene expressionin ASM cells.Methods: ASM cells were treated with BK, EGF, AG-1478 and genistein. IL-6 productionwas analyzed by enzyme-linked immunosorbent assay (ELISA.Immunoblot study was used for detection of ERK1/2 activation.Transactivation of EGFR phosphorylation was detected by immunoprecipitation.Results: ELISA showed that EGF (10 ng/ml, 18 hr increased IL-6 secretion (from234

  8. Bradykinin antagonists modified with dipeptide mimetic beta-turn inducers.

    Science.gov (United States)

    Alcaro, Maria C; Vinci, Valerio; D'Ursi, Anna M; Scrima, Mario; Chelli, Mario; Giuliani, Sandro; Meini, Stefania; Di Giacomo, Marcello; Colombo, Lino; Papini, Anna Maria

    2006-05-01

    Bradykinin (BK) is involved in a wide variety of pathophysiological processes. Potent BK peptide antagonists can be developed introducing constrained unnatural amino acids, necessary to force the secondary structure of the molecule. In this paper, we report a structure-activity relationship study of two peptide analogues of the potent B2 antagonist HOE 140 by replacing the D-Tic-Oic dipeptide with conformationally constrained dipeptide mimetic beta-turn inducers. PMID:16504505

  9. Kinin B2 receptor regulates chemokines CCL2 and CCL5 expression and modulates leukocyte recruitment and pathology in experimental autoimmune encephalomyelitis (EAE in mice

    Directory of Open Access Journals (Sweden)

    Bader Michael

    2008-11-01

    Full Text Available Abstract Background Kinins are important mediators of inflammation and act through stimulation of two receptor subtypes, B1 and B2. Leukocyte infiltration contributes to the pathogenesis of autoimmune inflammation in the central nervous system (CNS, occurring not only in multiple sclerosis (MS but also in experimental autoimmune encephalomyelitis (EAE. We have previously shown that the chemokines CCL2 and CCL5 play an important role in the adhesion of leukocytes to the brain microcirculation in EAE. The aim of the present study was to evaluate the relevance of B2 receptors to leukocyte-endothelium interactions in the cerebral microcirculation, and its participation in CNS inflammation in the experimental model of myelin-oligodendrocyte-glycoprotein (MOG35–55-induced EAE in mice. Methods In order to evaluate the role of B2 receptor in the cerebral microvasculature we used wild-type (WT and kinin B2 receptor knockout (B2-/- mice subjected to MOG35–55-induced EAE. Intravital microscopy was used to investigate leukocyte recruitment on pial matter vessels in B2-/- and WT EAE mice. Histological documentation of inflammatory infiltrates in brain and spinal cords was correlated with intravital findings. The expression of CCL5 and CCL2 in cerebral tissue was assessed by ELISA. Results Clinical parameters of disease were reduced in B2-/- mice in comparison to wild type EAE mice. At day 14 after EAE induction, there was a significant decrease in the number of adherent leukocytes, a reduction of cerebral CCL5 and CCL2 expressions, and smaller inflammatory and degenerative changes in B2-/- mice when compared to WT. Conclusion Our results suggest that B2 receptors have two major effects in the control of EAE severity: (i B2 regulates the expression of chemokines, including CCL2 and CCL5, and (ii B2 modulates leukocyte recruitment and inflammatory lesions in the CNS.

  10. Cellular localization of kinin B1 receptor in the spinal cord of streptozotocin-diabetic rats with a fluorescent [Nα-Bodipy]-des-Arg9-bradykinin

    Directory of Open Access Journals (Sweden)

    Gaudreau Pierrette

    2009-03-01

    Full Text Available Abstract Background The kinin B1 receptor (B1R is upregulated by pro-inflammatory cytokines, bacterial endotoxins and hyperglycaemia-induced oxidative stress. In animal models of diabetes, it contributes to pain polyneuropathy. This study aims at defining the cellular localization of B1R in thoracic spinal cord of type 1 diabetic rats by confocal microscopy with the use of a fluorescent agonist, [Nα-Bodipy]-des-Arg9-BK (BdABK and selective antibodies. Methods Diabetes was induced by streptozotocin (STZ; 65 mg/kg, i.p.. Four days post-STZ treatment, B1R expression was confirmed by quantitative real-time PCR and autoradiography. The B1R selectivity of BdABK was determined by assessing its ability to displace B1R [125I]-HPP-desArg10-Hoe140 and B2R [125I]-HPP-Hoe 140 radioligands. The in vivo activity of BdABK was also evaluated on thermal hyperalgesia. Results B1R was increased by 18-fold (mRNA and 2.7-fold (binding sites in the thoracic spinal cord of STZ-treated rats when compared to control. BdABK failed to displace the B2R radioligand but displaced the B1R radioligand (IC50 = 5.3 nM. In comparison, IC50 values of B1R selective antagonist R-715 and B1R agonist des-Arg9-BK were 4.3 nM and 19 nM, respectively. Intraperitoneal BdABK and des-Arg9-BK elicited dose-dependent thermal hyperalgesia in STZ-treated rats but not in control rats. The B1R fluorescent agonist was co-localized with immunomarkers of microglia, astrocytes and sensory C fibers in the spinal cord of STZ-treated rats. Conclusion The induction and up-regulation of B1R in glial and sensory cells of the spinal cord in STZ-diabetic rats reinforce the idea that kinin B1R is an important target for drug development in pain processes.

  11. Bradykinin release avoids high molecular weight kininogen endocytosis.

    Directory of Open Access Journals (Sweden)

    Igor Z Damasceno

    Full Text Available Human H-kininogen (120 kDa plays a role in many pathophysiological processes and interacts with the cell surface through protein receptors and proteoglycans, which mediate H-kininogen endocytosis. In the present work we demonstrate that H-kininogen containing bradykinin domain is internalized and different endogenous kininogenases are present in CHO-K1 cells. We used CHO-K1 (wild type and CHO-745 (mutant deficient in proteoglycans biosynthesis cell lines. H-kininogen endocytosis was studied using confocal microscopy, and its hydrolysis by cell lysate fraction was determined by immunoblotting. Bradykinin release was also measured by radioimmunoassay. H-kininogen interaction with the cell surface of CHO-745 cells resulted in bradykinin release by serine proteases. In CHO-K1 cells, which produce heparan and chondroitin sulfate proteoglycans, internalization of H-kininogen through its bradykinin domain can occur on lipid raft domains/caveolae. Nevertheless bradykinin-free H-kininogen was not internalized by CHO-K1 cells. The H-kininogen present in acidic endosomal vesicles in CHO-K1 was approximately 10-fold higher than the levels in CHO-745. CHO-K1 lysate fractions were assayed at pH 5.5 and intact H-kininogen was totally hydrolyzed into a 62 kDa fragment. By contrast, at an assay pH 7.4, the remained fragments were 115 kDa, 83 kDa, 62 kDa and 48 kDa in size. The antipain-Sepharose chromatography separated endogenous kininogenases from CHO-K1 lysate fraction. No difference was detected in the assays at pH 5.5 or 7.4, but the proteins in the fraction bound to the resin released bradykinin from H-kininogen. However, the proteins in the unbound fraction cleaved intact H-kininogen at other sites but did not release bradykinin. H-kininogen can interact with extravascular cells, and is internalized dependent on its bradykinin domain and cell surface proteoglycans. After internalization, H-kininogen is proteolytically processed by intracellular

  12. Involvement of Intercellular Adhesion Molecule-1 Up-Regulation in Bradykinin Promotes Cell Motility in Human Prostate Cancers

    Directory of Open Access Journals (Sweden)

    Chih-Hsin Tang

    2013-06-01

    Full Text Available Prostate cancer is the most commonly diagnosed malignancy in men and shows a predilection for metastasis to distant organs. Bradykinin (BK is an inflammatory mediator and has recently been shown to mediate tumor growth and metastasis. The adhesion molecule intercellular adhesion molecule-1 (ICAM-1 plays a critical role during tumor metastasis. The aim of this study was to examine whether BK promotes prostate cancer cell migration via ICAM-1 expression. The motility of cancer cells was increased following BK treatment. Stimulation of prostate cancer cells with BK induced mRNA and protein expression of ICAM-1. Transfection of cells with ICAM-1 small interfering RNA reduced BK-increased cell migration. Pretreatment of prostate cancer cells with B2 receptor, phosphatidylinositol 3-kinase (PI3K, Akt, and activator protein 1 (AP-1 inhibitors or mutants abolished BK-promoted migration and ICAM-1 expression. In addition, treatment with a B2 receptor, PI3K, or Akt inhibitor also reduced BK-mediated AP-1 activation. Our results indicate that BK enhances the migration of prostate cancer cells by increasing ICAM-1 expression through a signal transduction pathway that involves the B2 receptor, PI3K, Akt, and AP-1. Thus, BK represents a promising new target for treating prostate cancer metastasis.

  13. Modulation of expression of the nuclear receptor NR0B2 (small heterodimer partner 1) and its impact on proliferation of renal carcinoma cells

    Science.gov (United States)

    Prestin, Katharina; Olbert, Maria; Hussner, Janine; Isenegger, Tamara L; Gliesche, Daniel G; Böttcher, Kerstin; Zimmermann, Uwe; Meyer zu Schwabedissen, Henriette E

    2016-01-01

    Mammalian nuclear receptors (NRs) are transcription factors regulating the expression of target genes that play an important role in drug metabolism, transport, and cellular signaling pathways. The orphan and structurally unique receptor small heterodimer partner 1 (syn NR0B2) is not only known for its modulation of drug response, but has also been reported to be involved in hepatocellular carcinogenesis. Indeed, previous studies show that NR0B2 is downregulated in human hepatocellular carcinoma, suggesting that NR0B2 acts as a tumor suppressor via inhibition of cellular growth and activation of apoptosis in this tumor entity. The aim of our study was to elucidate whether NR0B2 may also play a role in other tumor entities. Comparing NR0B2 expression in renal cell carcinoma and adjacent nonmalignant transformed tissue revealed significant downregulation in vivo. Additionally, the impact of heterologous expression of NR0B2 on cell cycle progression and proliferation in cells of renal origin was characterized. Monitoring fluorescence intensity of resazurin turnover in RCC-EW cells revealed no significant differences in metabolic activity in the presence of NR0B2. However, there was a significant decrease of cellular proliferation in cells overexpressing this NR, and NR0B2 was more efficient than currently used antiproliferative agents. Furthermore, flow cytometry analysis showed that heterologous overexpression of NR0B2 significantly reduced the amount of cells passing the G1 phase, while on the other hand, more cells in S/G2 phase were detected. Taken together, our data suggest that downregulation of NR0B2 may also play a role in renal cell carcinoma development and progression. PMID:27540300

  14. Tissue Kallikrein Alleviates Cerebral Ischemia-Reperfusion Injury by Activating the B2R-ERK1/2-CREB-Bcl-2 Signaling Pathway in Diabetic Rats

    Science.gov (United States)

    Yuan, Kunxiong; Hu, Bin; Sang, Hongfei; Xie, Yi; Xu, Lili; Cao, Qinqin; Chen, Xin; Zhao, Lingling; Liu, Xinfeng; Liu, Ling; Zhang, Renliang

    2016-01-01

    Diabetes mellitus (DM) substantially increases the risk of ischemic stroke and reduces the tolerance to ischemic insults. Tissue kallikrein (TK) has been demonstrated to protect neurons from ischemia/reperfusion (I/R) injury in orthoglycemic model by activating the bradykinin B2 receptor (B2R). Considering the differential effects of B2R or bradykinin B1 receptor (B1R) on cardioprotection and neuroprotection in I/R with or without diabetes, this study was designed to investigate the role of TK during cerebral I/R injury in streptozotocin-induced diabetic rats. Intravenous injection of TK inhibited apoptosis in neurons, alleviated edema and inflammatory reactions after focal cerebral I/R, significantly reduced the infarct volume, and improved functional recovery. These beneficial effects were accompanied by activation of the extracellular signal-regulated kinase 1/2 (ERK1/2), cAMP response element-binding (CREB), and Bcl-2 signal proteins. Inhibition of the B2R or ERK1/2 pathway abated the effects of TK, whereas an antagonist of B1R enhanced the effects. These findings reveal that the neuroprotective effect of TK against cerebral I/R injury in streptozotocin-induced diabetic rats mainly involves the enhancement of B2R and ERK1/2-CREB-Bcl-2 signaling pathway activity.

  15. Localization of relaxin receptors in arteries and veins, and region-specific increases in compliance and bradykinin-mediated relaxation after in vivo serelaxin treatment

    OpenAIRE

    Jelinic, Maria; Leo, Chen-Huei; Uiterweer, Emiel D. Post; Sandow, Shaun L.; Gooi, Jonathan H.; Wlodek, Mary E.; Conrad, Kirk P.; Parkington, Helena; Tare, Marianne; Parry, Laura J.

    2014-01-01

    Relaxin is a potent vasodilator of small resistance arteries and modifies arterial compliance in some systemic vascular beds, yet receptors for relaxin, such as RXFP1, have only been localized to vascular smooth muscle. This study first aimed to localize RXFP1 in rat arteries and veins from different organ beds and determine whether receptors are present in endothelial cells. We then tested the hypothesis that region-specific vascular effects of relaxin may be influenced by the cellular local...

  16. Intermittent hypoxia induces the proliferation of rat vascular smooth muscle cell with the increases in epidermal growth factor family and erbB2 receptor

    Energy Technology Data Exchange (ETDEWEB)

    Kyotani, Yoji, E-mail: cd147@naramed-u.ac.jp [Department of Pharmacology, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Department of Pharmacy, Nara Medical University Hospital, Kashihara 634-8522 (Japan); Ota, Hiroyo [Second Department of Internal Medicine, Nara Medical University School of Medicine, Kashihara 634-8522 (Japan); Department of Biochemistry, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Itaya-Hironaka, Asako; Yamauchi, Akiyo; Sakuramoto-Tsuchida, Sumiyo [Department of Biochemistry, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Zhao, Jing; Ozawa, Kentaro; Nagayama, Kosuke; Ito, Satoyasu [Department of Pharmacology, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Takasawa, Shin [Department of Biochemistry, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Kimura, Hiroshi [Second Department of Internal Medicine, Nara Medical University School of Medicine, Kashihara 634-8522 (Japan); Uno, Masayuki [Department of Pharmacy, Nara Medical University Hospital, Kashihara 634-8522 (Japan); Yoshizumi, Masanori [Department of Pharmacology, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan)

    2013-11-15

    Obstructive sleep apnea is characterized by intermittent hypoxia (IH), and associated with cardiovascular diseases, such as stroke and heart failure. These cardiovascular diseases have a relation to atherosclerosis marked by the proliferation of vascular smooth muscle cells (VSMCs). In this study, we investigated the influence of IH on cultured rat aortic smooth muscle cell (RASMC). The proliferation of RASMC was significantly increased by IH without changing the level of apoptosis. In order to see what induces RASMC proliferation, we investigated the influence of normoxia (N)-, IH- and sustained hypoxia (SH)-treated cell conditioned media on RASMC proliferation. IH-treated cell conditioned medium significantly increased RASMC proliferation compared with N-treated cell conditioned medium, but SH-treated cell conditioned medium did not. We next investigated the epidermal growth factor (EGF) family as autocrine growth factors. Among the EGF family, we found significant increases in mRNAs for epiregulin (ER), amphiregulin (AR) and neuregulin-1 (NRG1) in IH-treated cells and mature ER in IH-treated cell conditioned medium. We next investigated the changes in erbB family receptors that are receptors for ER, AR and NRG1, and found that erbB2 receptor mRNA and protein expressions were increased by IH, but not by SH. Phosphorylation of erbB2 receptor at Tyr-1248 that mediates intracellular signaling for several physiological effects including cell proliferation was increased by IH, but not by SH. In addition, inhibitor for erbB2 receptor suppressed IH-induced cell proliferation. These results provide the first demonstration that IH induces VSMC proliferation, and suggest that EGF family, such as ER, AR and NRG1, and erbB2 receptor could be involved in the IH-induced VSMC proliferation. - Highlights: ●In vitro system for intermittent hypoxia (IH) and sustained hypoxia (SH). ●IH, but not SH, induces the proliferation of rat vascular smooth muscle cell. ●Epiregulin m

  17. Expression of glutathione S-transferase B1, B2, Mu and Pi in breast cancers and their relationship to oestrogen receptor status.

    OpenAIRE

    Howie, A F; Miller, W. R.; Hawkins, R. A.; Hutchinson, A. R.; Beckett, G J

    1989-01-01

    The concentrations of glutathione S-transferase (GST) B1 and B2 (Alpha), Pi and Mu have been measured by radioimmunoassay in cytosols from 28 oestrogen receptor (ER) rich an 30 ER-poor breast tumours. GST B1, B2 and Pi was detected in all 58 breast tumour cytosols whilst GST Mu was found in only 28. Of the GSTs, Pi was expressed most strongly in all cytosols and the concentration was significantly higher in ER-poor tumour cytosols than in ER-rich tumours (P less than 0.01). As with GST Pi, th...

  18. Localization of relaxin receptors in arteries and veins, and region-specific increases in compliance and bradykinin-mediated relaxation after in vivo serelaxin treatment.

    Science.gov (United States)

    Jelinic, Maria; Leo, Chen-Huei; Post Uiterweer, Emiel D; Sandow, Shaun L; Gooi, Jonathan H; Wlodek, Mary E; Conrad, Kirk P; Parkington, Helena; Tare, Marianne; Parry, Laura J

    2014-01-01

    Relaxin is a potent vasodilator of small resistance arteries and modifies arterial compliance in some systemic vascular beds, yet receptors for relaxin, such as RXFP1, have only been localized to vascular smooth muscle. This study first aimed to localize RXFP1 in rat arteries and veins from different organ beds and determine whether receptors are present in endothelial cells. We then tested the hypothesis that region-specific vascular effects of relaxin may be influenced by the cellular localization of RXFP1 within different blood vessels. The aorta, vena cava, mesenteric artery, and vein had significantly higher (PRXFP1 immunostaining in endothelial cells compared with vascular smooth muscle, whereas the femoral artery and vein and small pulmonary arteries had higher (PRXFP1 immunostaining in the vascular smooth muscle. Male rats were treated subcutaneously with recombinant human relaxin-2 (serelaxin; 4 μg/h) for 5 d; vasodilation and compliance in mesenteric and femoral arteries and veins were compared with placebo controls. Serelaxin significantly (P=0.04) reduced wall stiffness and increased volume compliance in mesenteric arteries but not in the other vessels examined. This was associated with changes in geometrical properties, and not compositional changes in the extracellular matrix. Serelaxin treatment had no effect on acetylcholine-mediated relaxation but significantly (PRXFP1 on endothelial and smooth muscle across the vasculature. In rats, mesenteric arteries exhibit the greatest functional response to chronic serelaxin treatment. PMID:24036884

  19. Simultaneous suppression of epidermal growth factor receptor and c-erbB-2 reverses aneuploidy and malignant phenotype of a human ovarian carcinoma cell line.

    Science.gov (United States)

    Pack, Svetlana D; Alper, Ozgül M; Stromberg, Kurt; Augustus, Meena; Ozdemirli, Metin; Miermont, Anne M; Klus, Greg; Rusin, Marek; Slack, Rebecca; Hacker, Neville F; Ried, Thomas; Szallasi, Zoltan; Alper, Ozge

    2004-02-01

    Coexpression of epidermal growth factor receptor (EGFR) and c-erbB-2 in 47-68% of ovarian cancer cells indicate their strong association with tumor formation. We examined the effects of simultaneous antisense- or immunosuppression of EGFR and c-erbB-2 expression on the invasive phenotype, aneuploidy, and genotype of cultured human ovarian carcinoma cells (NIH:OVCAR-8). We report here that suppression of both EGFR and c-erbB-2 results in regression of aneuploidy and genomic imbalances in NIH:OVCAR-8 cells, restores a more normal phenotype, and results in a more normal gene expression profile. Combined with cytogenetic analysis, our data demonstrate that the regression of aneuploidy is due to the selective apoptosis of double antisense transfected cells with highly abnormal karyotype. PMID:14871800

  20. Antiserum raised against a synthetic phosphotyrosine-containing peptide selectively recognizes p185neu/erbB-2 and the epidermal growth factor receptor.

    OpenAIRE

    Bangalore, L; Tanner, A J; Laudano, A P; Stern, D F

    1992-01-01

    Rabbits were immunized with a synthetic phosphopeptide corresponding to a major autophosphorylation site of p185neu/erbB2 to determine the feasibility of producing tyrosine-phosphopeptide-specific antibodies. A series of adsorption and affinity chromatography steps were used to select antibodies with the desired reactivity. Immunoblot experiments showed that the resulting serum is highly specific for tyrosine-phosphorylated forms of p185 and the related epidermal growth factor receptor. The s...

  1. 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

    OpenAIRE

    Widya Kusumawati; Kusnarman Keman; Setyawati Soeharto

    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 preeclampti...

  2. Assessment of staging, prognosis and mortality of colorectal cancer by tumor markers: receptor erbB-2 and cadherins

    Directory of Open Access Journals (Sweden)

    Jesus Eliane C.

    2005-01-01

    Full Text Available PURPOSE: To evaluate the prognostic significance and correlation with staging and degree of cell differentiation of the tumoral expression of the proteins c-erbB-2 and E-cadherin, in patients with colorectal adenocarcinoma. METHODS: The study included 117 patients with an average age of 63.1 years and an average follow-up duration of 28.1 months. The disease-free interval, survival, incidence of recurrence and specific mortality were evaluated. c-erbB-2 anti-oncoprotein antibodies (Dako were utilized via the streptavidin-biotin technique. Samples were considered to be positive for c-erbB-2 if 10% or more of the tumor cell membranes were stained.The anti-E-cadherin antibodies (Dako, evaluated this protein and is considered positive, if 50% or more of the cell membranes were stained. Statistical analysis was performed using Pearson's chi-squared test, Fisher's exact test, Kaplan-Meier's estimator, the log-rank test and Wilcoxon's test (Breslow version, setting the level of statistical significance at 5% (p<0.05. RESULTS: 52 of 108 patients studied for c-erbB-2 were positive (48,1%, 47 of 93 patients studied for E-cadherin were negative (50,5%. These data do not express any correlation with TNM (tumor, node and metastasis staging and the degree of cell differentiation or with the tumor recurrence rate. The disease-free interval among patients who were positive for c-erbB-2 and negative for E-cadherin was 68.0 months and did not differ from those with c-erbB-2 negative and E-cadherin positive ( 55.0 months - p = 0.5510. The average survival among patients positive for c-erbB-2 and negative for E-cadherin was 75 months without statistical significance difference with the other group ( 61 months - p = 0.5256. Specific mortality occurred in 20.0% of the cases and did not correlate with the expression of c-erbB-2 (p=0,446, E-cadherin (p=0,883. CONCLUSION: The tumoral expression of c-erbB-2 and E-cadherin did not demonstrate a correlation with the

  3. 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). PMID:26989513

  4. Electrocardiographic Characterization of Cardiac Hypertrophy in Mice that Overexpress the ErbB2 Receptor Tyrosine Kinase

    DEFF Research Database (Denmark)

    Sysa-Shah, Polina; Sørensen, Lars L; Abraham, M Roselle;

    2015-01-01

    Electrocardiography is an important method for evaluation and risk stratification of patients with cardiac hypertrophy. We hypothesized that the recently developed transgenic mouse model of cardiac hypertrophy (ErbB2(tg)) will display distinct ECG features, enabling WT (wild type) mice to be......, the ECG recordings of ErbB2(tg) mice were characterized by higher P- and R-wave amplitudes, broader QRS complexes, inverted T waves, and ST interval depression. Pearson's correlation matrix analysis of combined WT and ErbB2(tg) data revealed significant correlation between heart weight and the ECG...... distinguished from transgenic mice without using conventional PCR genotyping. We evaluated more than 2000 mice and developed specific criteria for genotype determination by using cageside ECG, during which unanesthetized mice were manually restrained for less than 1 min. Compared with those from WT counterparts...

  5. Bradykinin preconditioning improves therapeutic potential of human endothelial progenitor cells in infarcted myocardium.

    Directory of Open Access Journals (Sweden)

    Zulong Sheng

    Full Text Available OBJECTIVES: Stem cell preconditioning (PC is a powerful approach in reducing cell death after transplantation. We hypothesized that PC human endothelial progenitor cells (hEPCs with bradykinin (BK enhance cell survival, inhibit apoptosis and repair the infarcted myocardium. METHODS: The hEPCs were preconditioned with or without BK. The hEPCs apoptosis induced by hypoxia along with serum deprivation was determined by annexin V-fluorescein isothiocyanate/ propidium iodide staining. Cleaved caspase-3, Akt and eNOS expressions were determined by Western blots. Caspase-3 activity and vascular endothelial growth factor (VEGF levels were assessed in hEPCs. For in vivo studies, the survival and cardiomyocytes apoptosis of transplanted hEPCs were assessed using 1,1'-dioctadecyl-3,3,3',3'-tetramethylindodi- carbocyanine,4-chlorobenzenesul-fonate salt labeled hEPCs and TUNEL staining. Infarct size and cardiac function were measured at 10 days after transplantation, and the survival of transplanted hEPCs were visualized using near-infrared optical imaging. RESULTS: In vitro data showed a marked suppression in cell apoptosis following BK PC. The PC reduced caspase-3 activation, increased the Akt, eNOS phosphorylation and VEGF levels. In vivo data in preconditioned group showed a robust cell anti-apoptosis, reduction in infarct size, and significant improvement in cardiac function. The effects of BK PC were abrogated by the B2 receptor antagonist HOE140, the Akt and eNOS antagonists LY294002 and L-NAME, respectively. CONCLUSIONS: The activation of B2 receptor-dependent PI3K/Akt/eNOS pathway by BK PC promotes VEGF secretion, hEPC survival and inhibits apoptosis, thereby improving cardiac function in vivo. The BK PC hEPC transplantation for stem cell-based therapies is a novel approach that has potential for clinical used.

  6. Differential release of eicosanoids by bradykinin, arachidonic acid and calcium ionophore A23187 in guinea-pig isolated perfused lung.

    OpenAIRE

    Bakhle, Y. S.; Moncada, S.; de Nucci, G.; Salmon, J A

    1985-01-01

    The effects of infusions of bradykinin (0.2 microM), calcium ionophore A23187 (0.5 microM) and arachidonic acid (13 microM) on the release of eicosanoids from the guinea-pig isolated perfused lung were investigated using radioimmunoassay for thromboxane B2 (TXB2), 6-oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha), PGE2, leukotriene B4 (LTB4) and LTC4 and bioassay using the superfusion cascade. Bradykinin released more 6-oxo-PGF1 alpha than TXB2, whereas arachidonic acid and ionophore released m...

  7. NBCn1 and NHE1 expression and activity in DeltaNErbB2 receptor-expressing MCF-7 breast cancer cells: contributions to pHi regulation and chemotherapy resistance

    DEFF Research Database (Denmark)

    Lauritzen, G; Jensen, M B F; Bødtkjer, Ebbe;

    2010-01-01

    Altered pH-regulatory ion transport is characteristic of many cancers; however, the mechanisms and consequences are poorly understood. Here, we investigate how a truncated, constitutively active ErbB2 receptor (DeltaNErbB2) common in breast cancer impacts on the Na(+)/H(+)-exchanger NHE1 and the ...

  8. TRPA1 in bradykinin-induced mechanical hypersensitivity of vagal C fibers in guinea pig esophagus.

    Science.gov (United States)

    Yu, Shaoyong; Ouyang, Ann

    2009-02-01

    Bradykinin (BK) activates sensory nerves and causes hyperalgesia. Transient receptor potential A1 (TRPA1) is expressed in sensory nerves and mediates cold, mechanical, and chemical nociception. TRPA1 can be activated by BK. TRPA1 knockout mice show impaired responses to BK and mechanical nociception. However, direct evidence from sensory nerve terminals is lacking. This study aims to determine the role of TRPA1 in BK-induced visceral mechanical hypersensitivity. Extracellular recordings of action potentials from vagal nodose and jugular neurons are performed in an ex vivo guinea pig esophageal-vagal preparation. Peak frequencies of action potentials of afferent nerves evoked by esophageal distension and chemical perfusion are recorded and compared. BK activates most nodose and all jugular C fibers. This activation is repeatable and associated with a significant increase in response to esophageal distension, which can be prevented by the B2 receptor antagonist WIN64338. TRPA1 agonist allyl isothiocyanate (AITC) activates most BK-positive nodose and jugular C fibers. This is associated with a transient loss of response to mechanical distensions and desensitization to a second AITC perfusion. Desensitization with AITC and pretreatment with TRPA1 inhibitor HC-030031 both inhibit BK-induced mechanical hypersensitivity but do not affect BK-evoked activation in nodose and jugular C fibers. In contrast, esophageal vagal afferent Adelta fibers do not respond to BK or AITC and fail to show mechanical hypersensitivity after BK perfusion. This provides the first evidence directly from visceral sensory afferent nerve terminals that TRPA1 mediates BK-induced mechanical hypersensitivity. This reveals a novel mechanism of visceral peripheral sensitization. PMID:19033534

  9. Role of Bradykinin on Left Ventricular Remodeling and Cardiac Function after Myocardial Infarction in Rats

    Institute of Scientific and Technical Information of China (English)

    Hai-zhu ZHANG; Li-quan LEI; Chang-cong CUI; Jian LIU

    2009-01-01

    Objectives To investigate the influences of bradykinin (BK) on hemodynamics, left ventricular hypertrophy and interstitial collagen metabolism after myocardial infarction (MI) in rats and the contribution of BK in angiotensin-con-verting enzyme (ACE) inhibition therapy. Methods By means of hemodynamic measurements, morphometric study of myocyte hypertrophy and SDS-PAGE technique ,the effects of enalapril pressure (500μg·kg-1·day-1) ,enalapril(500μg·kg-1·day-1) with BK B2 receptor antagonist Hoe-140 (500μg·kg-1·day-1),angiotensin Ⅱ (AgII) type 1 (AT1) receptor antagonist losartan(3mg·kg-1·day-1)on mean arterial pressure (MAP) ,left ventricular end-dias-tolic pressure (LVEDP), as well as maximum positive left ventricular pressure change (+ dp/dtmax), Ⅴ(m) n, col-lagen content and the ratio of type Ⅰ to type Ⅲ collagen (Ⅰ / Ⅲ) of noninfarcted area were observed in rats after MI. Treatments were started on the 3rd day after MI and continued for another 28 days. Results Enalapril reduced LV-EDP, Ⅴ(m) n and collagen content as well as collagen Ⅰ/Ⅲ compared with the untreated MI group (P < 0. 05), and all of these effects of enalapril were partly blunted by concomitant treatment with hoe-140 (P < 0. 05). Losartan was less effective than enalapril (P < 0. 05). However, three treatment groups had no significant differences in + dp/dtmax and had similar reductions in MAP compared with untreated MI group. Conclusions BK can improve cardiac function and prevent left ventricular hypertrophy with myocardial fibrosis independent of blood pressure. The mechanisms of ACEI are both blockade of Ang Ⅱ formation and inhibition of BK degradation.

  10. Inflammatory mediator bradykinin increases population of sensory neurons expressing functional T-type Ca2+ channels

    Science.gov (United States)

    Huang, Dongyang; Liang, Ce; Zhang, Fan; Men, Hongchao; Du, Xiaona; Gamper, Nikita; Zhang, Hailin

    2016-01-01

    T-type Ca2+ channels are important regulators of peripheral sensory neuron excitability. Accordingly, T-type Ca2+ currents are often increased in various pathological pain conditions, such as inflammation or nerve injury. Here we investigated effects of inflammation on functional expression of T-type Ca2+ channels in small-diameter cultured dorsal root ganglion (DRG) neurons. We found that overnight treatment of DRG cultures with a cocktail of inflammatory mediators bradykinin (BK), adenosine triphosphate (ATP), norepinephrine (NE) and prostaglandin E2 (PGE2) strongly increased the population size of the small-diameter neurons displaying low-voltage activated (LVA, T-type) Ca2+ currents while having no effect on the peak LVA current amplitude. When applied individually, BK and ATP also increased the population size of LVA-positive neurons while NE and PGE2 had no effect. The PLC inhibitor U-73122 and B2 receptor antagonist, Hoe-140, both abolished the increase of the population of LVA-positive DRG neurons. Inflammatory treatment did not affect CaV3.2 mRNA or protein levels in DRG cultures. Furthermore, an ubiquitination inhibitor, MG132, did not increase the population of LVA-positive neurons. Our data suggest that inflammatory mediators BK and ATP increase the abundance of LVA-positive DRG neurons in total neuronal population by stimulating the recruitment of a ‘reserve pool’ of CaV3.2 channels, particularly in neurons that do not display measurable LVA currents under control conditions. PMID:26944020

  11. Inflammatory mediator bradykinin increases population of sensory neurons expressing functional T-type Ca(2+) channels.

    Science.gov (United States)

    Huang, Dongyang; Liang, Ce; Zhang, Fan; Men, Hongchao; Du, Xiaona; Gamper, Nikita; Zhang, Hailin

    2016-04-29

    T-type Ca(2+) channels are important regulators of peripheral sensory neuron excitability. Accordingly, T-type Ca(2+) currents are often increased in various pathological pain conditions, such as inflammation or nerve injury. Here we investigated effects of inflammation on functional expression of T-type Ca(2+) channels in small-diameter cultured dorsal root ganglion (DRG) neurons. We found that overnight treatment of DRG cultures with a cocktail of inflammatory mediators bradykinin (BK), adenosine triphosphate (ATP), norepinephrine (NE) and prostaglandin E2 (PGE2) strongly increased the population size of the small-diameter neurons displaying low-voltage activated (LVA, T-type) Ca(2+) currents while having no effect on the peak LVA current amplitude. When applied individually, BK and ATP also increased the population size of LVA-positive neurons while NE and PGE2 had no effect. The PLC inhibitor U-73122 and B2 receptor antagonist, Hoe-140, both abolished the increase of the population of LVA-positive DRG neurons. Inflammatory treatment did not affect CaV3.2 mRNA or protein levels in DRG cultures. Furthermore, an ubiquitination inhibitor, MG132, did not increase the population of LVA-positive neurons. Our data suggest that inflammatory mediators BK and ATP increase the abundance of LVA-positive DRG neurons in total neuronal population by stimulating the recruitment of a 'reserve pool' of CaV3.2 channels, particularly in neurons that do not display measurable LVA currents under control conditions. PMID:26944020

  12. Unraveling the Pivotal Role of Bradykinin in ACE Inhibitor Activity.

    Science.gov (United States)

    Taddei, Stefano; Bortolotto, L

    2016-10-01

    Historically, the first described effect of an angiotensin converting enzyme (ACE) inhibitor was an increased activity of bradykinin, one of the substrates of ACE. However, in the subsequent years, molecular models describing the mechanism of action of ACE inhibitors in decreasing blood pressure and cardiovascular risk have focused mostly on the renin-angiotensin system. Nonetheless, over the last 20 years, the importance of bradykinin in regulating vasodilation, natriuresis, oxidative stress, fibrinolysis, inflammation, and apoptosis has become clearer. The affinity of ACE appears to be higher for bradykinin than for angiotensin I, thereby suggesting that ACE inhibitors may be more effective inhibitors of bradykinin degradation than of angiotensin II production. Data describing the effect of ACE inhibition on bradykinin signaling support the hypothesis that the most cardioprotective benefits attributed to ACE inhibition may be due to increased bradykinin signaling rather than to decreased angiotensin II signaling, especially when high dosages of ACE inhibitors are considered. In particular, modulation of bradykinin in the endothelium appears to be a major target of ACE inhibition. These new mechanistic concepts may lead to further development of strategies enhancing the bradykinin signaling. PMID:27260014

  13. Non-histaminergic angioedema: focus on bradykinin-mediated angioedema.

    Science.gov (United States)

    Busse, P J; Buckland, M S

    2013-04-01

    Angioedema is a result of increased vascular permeability, with subsequent extravasation of intravascular fluid into the surrounding tissues. Angioedema may be mediated by histamine, bradykinin or other mediators. Histaminergic angioedema generally presents with urticaria and/or pruritus and will respond to conventional treatment with antihistamines, corticosteroids or epinephrine. Bradykinin-mediated angioedema, which includes hereditary angioedema (HAE types I, II and III), acquired C1-INH deficiency, and angiotensin-converting enzyme inhibitor-induced angioedema does not typically present with urticaria/weals and does not respond to conventional agents such as antihistamines or corticosteroids. In recent years, several agents that prevent the generation or activity of bradykinin have been developed for the treatment of HAE types I and II and are also being evaluated in other types of bradykinin-mediated angioedema. These agents have the potential to improve outcomes for patients with different forms of bradykinin-mediated angioedema. PMID:23517034

  14. Bradykinin induced wheal and flare is not mediated by histamine release or cyclooxygenase products.

    OpenAIRE

    Crossman, D C; Fuller, R W

    1988-01-01

    The wheal and flare response to intradermal bradykinin was studied in man. The possibility that histamine and cyclooxygenase products are involved in the response to bradykinin was examined. Terfenadine given by mouth significantly inhibited the cutaneous response to histamine but the effect of bradykinin was unaltered. Similarly the cutaneous response to bradykinin was unchanged by aspirin.

  15. Construction of pB2R-Venus eukaryotic expression vectors and its expression in HEK293T cells%pB2 R-Venus 重组真核载体的构建及在 HEK293T细胞中的表达

    Institute of Scientific and Technical Information of China (English)

    季丙元; 程葆华; 王春梅; 陈京; 白波

    2014-01-01

    目的:构建带有黄色荧光蛋白突变体 Venus标签的人缓激肽2型受体(bradykinin receptor 2, B2R)真核表达载体,用于B2R与相关受体及蛋白的相互作用、B2R受体介导的信号转导机制的研究等。方法根据人B2R基因序列设计引物,以质粒pcDNA3.1-B2R为模板,PCR扩增目的基因人B2R。EcoRⅠ和BamHⅠ双酶切扩增产物及质粒pVenus-N1,经回收、连接、转化,获取重组质粒。对重组质粒进行酶切、测序鉴定。转染重组质粒至 HEK293T细胞,荧光显微镜观察受体B2R的细胞定位,蛋白印迹法检测目的蛋白人B2R蛋白的表达。结果 PCR扩增出了1条长度为1176 bp的基因片段,测序结果与GenBank (AY275465)相同。荧光显示B2R表达于质膜。Western blot结果显示,实验组蛋白印迹条带与目的蛋白大小相同,为44kDa。结论成功构建了pB2R-Venus重组真核表达载体,瞬时转染成功,获得了转染有重组质粒的HEK293T细胞。成功构建的重组质粒pB2R-Venus可用于后续BRET、FRET等实验研究,有助于B2R介导的信号转导机制的探讨和药物靶点的寻找。%Objective To investigate the interaction between B2R and other receptors ,and signal transduction mechanism ,human eukaryotic expression vector that bradykinin receptor 2 fused with Venus was constructed . Methods The primer was designed based on human B2R gene sequence ,and B2R gene was then amplified by PCR using plasmid pcDNA3 .1-B2R as template .The PCR product was digested by enzyme EcoRⅠand BamH ,and cloned into plasmid pV enus-N1 .The construct was identified by DNA sequencing .The recombinant plasmid was transiently transfected into HEK293T cells .Cell location and protein expression was detected by confocal microscopy and Western blot ,respectively .Results The fragment of 1176bp was amplified by PCR ,and its sequence was identical with the gene in Genebank (AY275465) .It is shown that the B2R expressed on

  16. Nicotine impairs cyclooxygenase-2-dependent kinin-receptor-mediated murine airway relaxations

    International Nuclear Information System (INIS)

    Introduction: Cigarette smoke induces local inflammation and airway hyperreactivity. In asthmatics, it worsens the symptoms and increases the risk for exacerbation. The present study investigates the effects of nicotine on airway relaxations in isolated murine tracheal segments. Methods: Segments were cultured for 24 h in the presence of vehicle, nicotine (10 μM) and/or dexamethasone (1 μM). Airway relaxations were assessed in myographs after pre-contraction with carbachol (1 μM). Kinin receptors, cyclooxygenase (COX) and inflammatory mediator expressions were assessed by real-time PCR and confocal-microscopy-based immunohistochemistry. Results: The organ culture procedure markedly increased bradykinin- (selective B2 receptor agonist) and des-Arg9-bradykinin- (selective B1 receptor agonist) induced relaxations, and slightly increased relaxation induced by isoprenaline, but not that induced by PGE2. The kinin receptor mediated relaxations were epithelium-, COX-2- and EP2-receptor-dependent and accompanied by drastically enhanced mRNA levels of kinin receptors, as well as inflammatory mediators MCP-1 and iNOS. Increase in COX-2 and mPGES-1 was verified both at mRNA and protein levels. Nicotine selectively suppressed the organ-culture-enhanced relaxations induced by des-Arg9-bradykinin and bradykinin, at the same time reducing mPGES-1 mRNA and protein expressions. α7-nicotinic acetylcholine receptor inhibitors α-bungarotoxin and MG624 both blocked the nicotine effects on kinin B2 receptors, but not those on B1. Dexamethasone completely abolished kinin-induced relaxations. Conclusion: It is tempting to conclude that a local inflammatory process per se could have a bronchoprotective component by increasing COX-2 mediated airway relaxations and that nicotine could impede this safety mechanism. Dexamethasone further reduced airway inflammation together with relaxations. This might contribute to the steroid resistance seen in some patients with asthma. - Highlights:

  17. Indicadores de Prognóstico em Câncer de Mama com Axila Negativa: Receptor de Estrógeno e Expressão de P53 e de c-erbB-2 Prognostic Indicators In Lymph Node-Negative Breast Cancer: Estrogen Receptor and P53 and c-erbB-2 Protein Expression

    Directory of Open Access Journals (Sweden)

    Adriana Harter Teixeira Bolaséll

    2000-08-01

    Full Text Available Objetivo: avaliar o valor prognóstico do receptor de estrógeno e da expressão das proteínas p53 e c-erbB-2 no câncer de mama com axila negativa. Métodos: foi realizado estudo imuno-histoquímico em material incluido em parafina, do arquivo do Instituto de Pesquisas Cito-Oncológicas (IPCO da Fundação Faculdade Federal de Ciências Médicas de Porto Alegre (FFFCMPA, de 50 casos de câncer de mama sem comprometimento dos linfonodos axilares, em mulheres menopausadas, tratadas na Irmandade da Santa Casa de Porto Alegre (ISCMPA e no Hospital Santa Rita de Porto Alegre (HSR de janeiro 1990 a dezembro de 1994. Para análise estatística foram utilizados os testes de c² com correção de Yates, teste exato de Fisher e curvas de sobrevida pelo método de Kaplan-Meier comparados pelo teste log rank. O seguimento médio das pacientes foi de 3,6 anos (3,1-4,5. Dos 50 casos, 14 apresentaram recidiva no período observado. Resultados: a média de idade foi 61 anos (variação de 46 a 78 anos. A mastectomia radical modificada (MRM foi realizada em 35 pacientes (70% e 15 (30% foram submetidas a setorectomia com esvaziamento axilar e posterior radioterapia. Metade das pacientes que apresentaram recidiva apresentaram-na nos três primeiros anos após o diagnóstico. O tamanho médio do tumor foi 2,8 cm (1,98-3,13 e o tipo histológico mais freqüente foi o carcinoma ductal infiltrante de tipo histológico não-especial (92%, conforme a graduação histológica de Bloom e Richardson, sendo 3 grau I (6,6%, 35 grau II (76% e 8 grau III (17,4%; nos tumores que recidivaram não houve nenhum grau I, 9 (25,7% eram grau II e 3 (37,5% eram grau III. Em relação ao prognóstico, a taxa de intervalo livre de doença foi menor quando da associação de tumor pouco diferenciado (grau III com receptor de estrógeno negativo (p = 0,006, p53 positivo (p = 0,006 e c-erbB-2 positivo (p = 0,001. Conclusão: mulheres menopausadas com câncer de mama sem comprometimento

  18. Kinins and peptide receptors.

    Science.gov (United States)

    Regoli, Domenico; Gobeil, Fernand

    2016-04-01

    This paper is divided into two sections: the first contains the essential elements of the opening lecture presented by Pr. Regoli to the 2015 International Kinin Symposium in S. Paulo, Brazil on June 28th and the second is the celebration of Dr. Regoli's 60 years of research on vasoactive peptides. The cardiovascular homeostasis derives from a balance of two systems, the renin-angiotensin system (RAS) and the kallikrein-kinin system (KKS). The biologically active effector entity of RAS is angiotensin receptor-1 (AT-1R), and that of KKS is bradykinin B2 receptor (B2R). The first mediates vasoconstriction, the second is the most potent and efficient vasodilator. Thanks to its complex and multi-functional mechanism of action, involving nitric oxide (NO), prostacyclin and endothelial hyperpolarizing factor (EDHF). B2R is instrumental for the supply of blood, oxygen and nutrition to tissues. KKS is present on the vascular endothelium and functions as an autacoid playing major roles in cardiovascular diseases (CVDs) and diabetes. KKS exerts a paramount role in the prevention of thrombosis and atherosclerosis. Such knowledge emphasizes the already prominent value of the ACE-inhibitors (ACEIs) for the treatment of CVDs and diabetes. Indeed, the ACEIs, thanks to their double action (block of the RAS and potentiation of the KKS) are the ideal agents for a rational treatment of these diseases. PMID:26408609

  19. Combined inhibition of ErbB1/2 and Notch receptors effectively targets breast ductal carcinoma in situ (DCIS stem/progenitor cell activity regardless of ErbB2 status.

    Directory of Open Access Journals (Sweden)

    Gillian Farnie

    Full Text Available Pathways involved in DCIS stem and progenitor signalling are poorly understood yet are critical to understand DCIS biology and to develop new therapies. Notch and ErbB1/2 receptor signalling cross talk has been demonstrated in invasive breast cancer, but their role in DCIS stem and progenitor cells has not been investigated. We have utilised 2 DCIS cell lines, MCF10DCIS.com (ErbB2-normal and SUM225 (ErbB2-overexpressing and 7 human primary DCIS samples were cultured in 3D matrigel and as mammospheres in the presence, absence or combination of the Notch inhibitor, DAPT, and ErbB1/2 inhibitors, lapatinib or gefitinib. Western blotting was applied to assess downstream signalling. In this study we demonstrate that DAPT reduced acini size and mammosphere formation in MCF10DCIS.com whereas there was no effect in SUM225. Lapatinb reduced acini size and mammosphere formation in SUM225, whereas mammosphere formation and Notch1 activity were increased in MCF10DCIS.com. Combined DAPT/lapatinib treatment was more effective at reducing acini size in both DCIS cell lines. Mammosphere formation in cell lines and human primary DCIS was reduced further by DAPT/lapatinib or DAPT/gefitinib regardless of ErbB2 receptor status. Our pre-clinical human models of DCIS demonstrate that Notch and ErbB1/2 both play a role in DCIS acini growth and stem cell activity. We report for the first time that cross talk between the two pathways in DCIS occurs regardless of ErbB2 receptor status and inhibition of Notch and ErbB1/2 was more efficacious than either alone. These data provide further understanding of DCIS biology and suggest treatment strategies combining Notch and ErbB1/2 inhibitors should be investigated regardless of ErbB2 receptor status.

  20. Chemoprevention of 7, 12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamster cheek pouch by topical application of a dual inhibitor of epidermal growth factor receptor (EGFR) and ErbB2 tyrosine kinases

    OpenAIRE

    Sun, Zheng; Sood, Sandeep; Li, Ning; Yang, Peiying; Newman, Robert A.; Yang, Chung S.; Chen, Xiaoxin

    2007-01-01

    Oral cancer is a common neoplasm worldwide with tobacco and alcohol being the major etiological factors contributing to its pathogenesis. Epidermal growth factor receptor (EGFR) and ErbB2 are known to be involved in the development of oral cancer with the former up-regulated in up to 90% human cases. The goal of this study was to evaluate the chemopreventive effects of a dual inhibitor of EGFR and ErbB2 tyrosine kinases, GW2974, in the 7, 12-dimethylbenz[a]anthracene (DMBA)-induced hamster ch...

  1. Combined Inhibition of ErbB1/2 and Notch Receptors Effectively Targets Breast Ductal Carcinoma In Situ (DCIS) Stem/Progenitor Cell Activity Regardless of ErbB2 Status

    OpenAIRE

    Farnie, Gillian; Willan, Pamela M; Clarke, Robert B; Bundred, Nigel J

    2013-01-01

    Pathways involved in DCIS stem and progenitor signalling are poorly understood yet are critical to understand DCIS biology and to develop new therapies. Notch and ErbB1/2 receptor signalling cross talk has been demonstrated in invasive breast cancer, but their role in DCIS stem and progenitor cells has not been investigated. We have utilised 2 DCIS cell lines, MCF10DCIS.com (ErbB2-normal) and SUM225 (ErbB2-overexpressing) and 7 human primary DCIS samples were cultured in 3D matrigel and as ma...

  2. Label-Free Quantitation and Mapping of the ErbB2 Tumor Receptor by Multiple Protease Digestion with Data-Dependent (MS1 and Data-Independent (MS2 Acquisitions

    Directory of Open Access Journals (Sweden)

    Jason M. Held

    2013-01-01

    Full Text Available The receptor tyrosine kinase ErbB2 is a breast cancer biomarker whose posttranslational modifications (PTMs are a key indicator of its activation. Quantifying the expression and PTMs of biomarkers such as ErbB2 by selected reaction monitoring (SRM mass spectrometry has several limitations, including minimal coverage and extensive assay development time. Therefore, we assessed the utility of two high resolution, full scan mass spectrometry approaches, MS1 Filtering and SWATH MS2, for targeted ErbB2 proteomics. Endogenous ErbB2 immunoprecipitated from SK-BR-3 cells was in-gel digested with trypsin, chymotrypsin, Asp-N, or trypsin plus Asp-N in triplicate. Data-dependent acquisition with an AB SCIEX TripleTOF 5600 and MS1 Filtering data processing was used to assess peptide and PTM coverage as well as the reproducibility of enzyme digestion. Data-independent acquisition (SWATH was also performed for MS2 quantitation. MS1 Filtering and SWATH MS2 allow quantitation of all detected analytes after acquisition, enabling the use of multiple proteases for quantitative assessment of target proteins. Combining high resolution proteomics with multiprotease digestion enabled quantitative mapping of ErbB2 with excellent reproducibility, improved amino acid sequence and PTM coverage, and decreased assay development time compared to typical SRM assays. These results demonstrate that high resolution quantitative proteomic approaches are an effective tool for targeted biomarker quantitation.

  3. B2B marketing

    OpenAIRE

    Pospíšilová, Lucie

    2010-01-01

    The main goal of this bachelor thesis is to apply theoretical knowledge in B2B marketing to the example of marketing processes in a particular company, to evaluate the current situation of its activities with regard to B2B principles and to suggest relevant recommendations. The theoretical part focuses on specific characteristics of B2B marketing, describes its differences from marketing on consumer markets, deals with buying behaviour of organizations and specifies particular features of mar...

  4. Direct stimulation of angiotensin II type 2 receptor enhances spatial memory

    DEFF Research Database (Denmark)

    Jing, Fei; Mogi, Masaki; Sakata, Akiko;

    2012-01-01

    evaluated by the Morris water maze test in C57BL6 mice, but this effect was not observed in AT(2) receptor-deficient mice. However, C21-induced cognitive enhancement in C57BL6 mice was attenuated by coadministration of icatibant, a bradykinin B(2) receptor antagonist. Administration of C21 dose dependently......We examined the possibility that direct stimulation of the angiotensin II type 2 (AT(2)) receptor by a newly generated direct AT(2) receptor agonist, Compound 21 (C21), enhances cognitive function. Treatment with C21 intraperitoneal injection for 2 weeks significantly enhanced cognitive function...... cognitive decline in this model. These results suggest that a direct AT(2) receptor agonist, C21, enhances cognitive function at least owing to an increase in CBF, enhancement of f-EPSP, and neurite outgrowth in hippocampal neurons....

  5. Gene : CBRC-HSAP-14-0064 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available iens] emb|CAA60109.1| B2-bradykinin receptor gene [Homo sapiens] gb|AAP...CBRC-HSAP-14-0064 14 A Bradykinin receptors NONE BKRB2_HUMAN 0.0 100% ref|NP_000614....1| bradykinin receptor B2 [Homo sapiens] sp|P30411|BKRB2_HUMAN B2 bradykinin receptor (BK-2 receptor) (B2R)... gb|AAK56376.1|AF378542_1 bradykinin receptor B2 [Homo sapiens] emb|CAA60108.1| B-2 bradykinin receptor gene [Homo sap...32297.1| bradykinin receptor B2 [Homo sapiens] gb|AAH74895.1| Bradykinin receptor B2 [Homo sapiens] gb|AAH74

  6. Effect of Montelukast on bradykinin-induced contraction of isolated tracheal smooth muscle of guinea pig

    Directory of Open Access Journals (Sweden)

    A Noor

    2011-01-01

    Conclusion: It is concluded that montelukast significantly inhibits, in a dose-dependent manner, the bradykinin-induced contraction of the guinea pig tracheal smooth muscle, and alludes to an interaction between the bradykinin and leukotriene mediators.

  7. Comparative nasal effects of bradykinin and histamine: influence on nasal airways resistance and plasma protein exudation.

    OpenAIRE

    Rajakulasingam, K.; Polosa, R; Lau, L.C.; Church, M. K.; Holgate, S T; Howarth, P. H.

    1993-01-01

    BACKGROUND--Bradykinin may contribute to the pathogenesis of allergic rhinitis. Like histamine, nasal challenge with bradykinin induces rhinorrhoea, nasal blockage, and plasma protein leakage. Their comparative nasal potencies have not, however, been fully elucidated. METHODS--Three double blind, randomised, placebo controlled and cross-over studies were undertaken to compare objectively the nasal effects of bradykinin, histamine, and vehicle. RESULTS--Both bradykinin and histamine produced d...

  8. Bradykinin-stimulated prostaglandin synthesis in conscious rabbits.

    OpenAIRE

    Warren, J. B.; Ritter, J M; Hickling, N. E.; Barrow, S E

    1987-01-01

    1 Bradykinin was infused intravenously into conscious rabbits to determine its effect on the concentration of prostaglandins in plasma. 6-Oxo-prostaglandin (PG) F1 alpha, the stable hydrolysis product of prostacyclin, and 13,14-dihydro-15-oxo-PGF2 alpha, a metabolite derived from PGE2 and PGF2 alpha, were measured by gas chromatography-electron capture mass spectrometry. 2 Incremental infusions of bradykinin (0.4-3.2 micrograms kg-1 min-1) increased plasma concentrations of both 6-oxo-PGF1 al...

  9. Bradykinin-activated transmembrane signals are coupled via N/sub o/ or N/sub i/ to production of inositol 1,4,5-trisphosphate, a second messenger in NG108-15 neuroblastoma-glioma hybrid cells

    International Nuclear Information System (INIS)

    The addition of bradykinin to NG108-15 cells results in a transient hyperpolarization followed by prolonged cell depolarization. Injection of inositol 1,4,5-trisphosphate or Ca2+ into the cytoplasm of NG108-15 cells also elicits cell hyperpolarization followed by depolarization. Tetraethylammonium ions inhibit the hyperpolarizing response of cells to bradykinin or inositol 1,4,5-trisphosphate. Thus, the hyperpolarizing phase of the cell response may be due to inositol 1,4,5-trisphosphate-dependent release of stored 45Ca-labelled Ca2+ into the cytoplasm, which activates Ca2+-dependent K+ channels. The depolarizing phase of the cell response to bradykinin is due largely to inhibition of M channels, thereby decreasing the rate of K+ efflux from cells and, to a lesser extent, to activation of Ca2+-dependent ion channels and Ca2+ channels. In contrast, injection of inositol 1,4,5-trisphosphate or Ca2+ into the cytosol did not alter M channel activity. Incubation of NG108-15 cells with pertussis toxin inhibits bradykinin-dependent cell hyperpolarization and depolarization. Bradykinin stimulates low K/sub m/ GTPase activity and inhibits adenylate cyclase in NG108-15 membrane preparations but not in membranes prepared from cells treated with pertussis toxin. These results show that [bradykinin-receptor] complexes interact with N/sub o/ or N/sub i/ and suggest that N/sub o/ and/or N/sub i/ mediate the transduction of signals from bradykinin receptors to phospholipase C and adenylate cyclase

  10. Loss of receptor-mediated 86Rb efflux from pig aortic endothelial cells in culture.

    OpenAIRE

    Ager, A.; Martin, W

    1983-01-01

    The responsiveness of freshly-isolated and subcultured pig aortic endothelial cells to adenosine triphosphate (ATP), bradykinin and ionophore A23187 was compared by monitoring agonist-induced 86Rb efflux. ATP, bradykinin and ionophore A23187 stimulated 86Rb efflux from freshly-isolated cells. ATP and bradykinin, which act via specific receptors, were less effective at inducing 86Rb efflux from subcultured cells but ionophore A23187 was as effective on subcultured as on freshly-isolated cells....

  11. Plasma extravasation mediated by lipopolysaccharide-induction of kinin B1 receptors in rat tissues

    Directory of Open Access Journals (Sweden)

    Paulo Roberto Wille

    2001-01-01

    Full Text Available The present study was performed to: (a evaluate the effects of kinin B1 (Sar{D-Phe8}-des-Arg9-BK; 10 nmol/kg and B2 (bradykinin (BK; 10 nmol/kg receptor agonists on plasma extravasation in selected rat tissues; (b determine the contribution of a lipopolysaccharide (LPS (100 μ g/kg to the effects triggered by B1 and B2 agonists; and (c characterize the selectivity of B1 ({Leu8}desArg9-BK; 10 nmol/kg and B2 (HOE 140; 10 nmol/kg antagonists as inhibitors of this kinin-induced phenomenon. B1 and B2 agonists were shown to increase plasma extravasation in the duodenum, ileum and also in the urinary bladder of the rat. LPS pretreatment enhanced the plasma extravasation mediated only by the B1 agonist in the duodenum, ileum, trachea, main and segmentar bronchi. These effects were prevented by the B1. but not the B2 antagonist. In normal rats, the B2 antagonist inhibited the effect of B2 agonist in all the tissues analyzed. However, in LPS-treated rats, the B2 antagonist was ineffective in the urinary bladder.

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

    International Nuclear Information System (INIS)

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

  13. Carcinoma ductal in situ associado a carcinoma invasivo na mesma mama: análise do grau nuclear e da expressão das proteínas p53 e C-erbB-2 e dos receptores de estrógeno Ductal carcinoma in situ and invasive carcinoma in the same breast: evaluation of the nuclear grade and the expressions of proteins p53 and C-erbB-2 and estrogen receptors

    Directory of Open Access Journals (Sweden)

    Orlando José de Almeida

    2004-07-01

    Full Text Available OBJETIVOS: avaliar a variação do grau nuclear e da expressão das proteínas p53 e c-erbB-2 e dos receptores de estrógeno (RE no carcinoma ductal in situ (CDIS e no carcinoma invasivo, presentes na mesma mama. MÉTODOS: estudo descritivo retrospectivo com 38 mulheres com CDIS associado a carcinoma invasivo da mama. Foi avaliado o grau nuclear e o realizado estudo imunohistoquímico para expressão das proteínas p53 e c-erbB-2 e para os RE. Os casos considerados positivos para a expressão das proteínas e dos RE foram aqueles com contagem de células positivas igual ou superior a 10%. A concordância entre estas variáveis no componente in situ e invasivo foi avaliada pelo coeficiente kappa (k, interpretado de acordo com os critérios de Landis e Koch. O teste de MacNemar foi usado para testar diferenças entre os dois grupos. RESULTADOS: a concordância entre o grau nuclear e a expressão dos RE nos componentes in situ e invasivo foi de 0,89 para ambos, quase perfeita. A concordância para a expressão da proteína c-erbB-2 também foi considerada quase perfeita, com coeficiente de 0,84. Já a concordância entre a expressão da proteína p53 no componente in situ e no invasivo foi de 1,0, considerada perfeita. Não houve diferenças significativas entre o grau nuclear e as expressões das proteínas e dos RE nos componentes in situ e invasivo na mesma mama. CONCLUSÕES: existe concordância alta do grau nuclear e da expressão das proteínas p53 e c-erbB-2 no CDIS e no carcinoma invasivo presentes na mesma mama.OBJECTIVES: The aim of the present study was to evaluate the nuclear grade, the expressions of p53 and c-erbB-2 proteins, and the estrogen receptors (ER of 38 women with ductal carcinoma in situ (DCIS and invasive carcinoma of the same breast. METHODS: the protein profile of 38 women was investigated in a descriptive and retrospective study, through the immune-histochemical technique. The cut-off limit for positive staining was

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1990-02-26

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

  15. Bradykinin is a mediator of anaphylactoid reactions during hemodialysis with AN69 membranes

    OpenAIRE

    Verresen, Luc; Fink, Edwin; Lemke, Horst-Dieter; Vanrenterghem, Yves

    1994-01-01

    Bradykinin is a mediator of anaphylactoid reactions during hemodialysis with AN69 membranes. Anaphylactoid reactions (AR) are the most feared complications of hemodialysis. Recently, a high incidence of AR has been reported during dialysis with AN69 membranes in patients treated with ACE inhibitors. Plasma levels of C3a, histamine and bradykinin were measured in 12 patients at the onset of AR during dialysis with AN69. We also investigated bradykinin generation in 10 symptom-free patients dia...

  16. Anti-ErbB-2 monoclonal antibodies and ErbB-2-directed vaccines.

    Science.gov (United States)

    Yip, Yum L; Ward, Robyn L

    2002-01-01

    The tumour antigen ErbB-2 belongs to the epidermal growth factor receptor family. Numerous studies have shown that ErbB-2 is overexpressed in many cancers and it is prognostically important in a subset of malignancies. It is well recognised that this receptor has many characteristics that make it an excellent target for tumour-specific immunotherapy. One anti-ErbB-2 monoclonal antibody, Herceptin or TrastuzuMab, has already shown clinical efficacy for the treatment of metastatic breast cancer. However, despite this success, it is still currently unclear how monoclonal antibodies inhibit tumour growth in vivo. This review will summarise the biological activities of a range of anti-ErbB-2 Mabs, as well as their possible mechanisms of action. In addition, as an active mode of immunotherapy, the current vaccine strategies for inducing or enhancing ErbB-2-specific immunity will also be discussed. It is anticipated that a better understanding of the activities of anti-ErbB-2 Mabs will aid in the development of both passive and active immunotherapies against this important receptor. PMID:11807621

  17. Acute electrophysiological responses of bradykinin-stimulated human fibroblasts.

    Science.gov (United States)

    Estacion, M

    1991-05-01

    1. Acute responses to bradykinin in human dermal fibroblasts were studied at 20-24 degrees C using both the patch-clamp technique to monitor ion currents and Fura-2 fluorescence to monitor [Ca2+]i. 2. During subconfluent culture, human dermal fibroblasts can express a diversity of ion channels as described in the preceding paper. 3. When GTP (1 mM) was included in the pipette solution, two additional ion channel populations were transiently augmented in response to bradykinin stimulation. 4. The first is a component of outwardly rectifying current which reached maximal induction within 10-15 s after bradykinin addition (1 microM) and then decayed back to near baseline over 60 s. 5. Ion substitution experiments combined with tail current analysis indicate that the outward current is carried predominantly by K+. 6. Video imaging of single-cell Fura-2 fluorescence from both intact cells and patch-clamped cells showed temporal correlation of the K+ current modulation and the Ca2+ transients in response to bradykinin stimulation. 7. The calcium ionophore, ionomycin, caused both an increase in intracellular calcium and the augmentation of the outward K+ current. The amount of additional K+ current was correlated with [Ca2+]i levels and could be elicited even without the presence of GTP in the pipette. 8. Apamin, a blocker of Ca(2+)-activated K+ channels, inhibited (at 1 microM) the ionomycin-induced modulation of K+ current. 9. In addition, an inward current was transiently induced in response to bradykinin. This current was strictly dependent on the presence of GTP in the pipette solution. This current showed little voltage dependence, as evidenced by a linear current vs. voltage relation, and a reversal potential near but measurably more positive than 0 mV. 10. This current could be decoupled from the Ca2+ transient and be irreversibly induced by including GTP gamma S (100 microM) in the pipette solution. 11. Ion substitution experiments show that this is a non

  18. Radioimmunoassay of blood bradykinin: purification of blood extracts of prevent cross-reaction with endogenous kininogen

    International Nuclear Information System (INIS)

    Alcoholic extracts of blood collected for measurement of circulating bradykinin were analysed for co-extracted kininogen which would artificially elevate measured bradykinin levels. The blood extract contained a glycoprotein with identical chromatographic properties to kininogen. Bradykinin immmunoreactivity in the extract eluted as a single peak from an immunoaffinity column of anti-bradykinin IgG bound to Sepharose identically to both bradykinin and kininogen showing immunoidentity of these substances. Affinity chromatography on Concanavalin A-Sepharose or ion-exchange chromatography on CM-Sephadex C25 separated bradykinin and the glycoprotein which again eluted identically to kininogen. The decrease in measured values of blood bradykinin after purification of the extract on CM-Sephadex C25 was a similar amount to that calculated as cross-reactivity with the amount of co-extracted kininogen. Hence radioimmunoassay of bradykinin in ethanolic extracts of blood is inaccurate owing to the presence of co-extracted kininogen, and additional purification steps such as chromatography on CM-Sephadex C25 are mandatory for accurate assay by ligand binding techniques. (Auth.)

  19. DMPD: Multifunctional effects of bradykinin on glial cells in relation to potentialanti-inflammatory effects. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17669557 Multifunctional effects of bradykinin on glial cells in relation to potent... Epub 2007 Jun 27. (.png) (.svg) (.html) (.csml) Show Multifunctional effects of bradykinin on glial cells in relation to poten...nctional effects of bradykinin on glial cells in relation to potentialanti-inflammatory effects. Authors Nod

  20. Effect of Shuyu Capsule Contained Serum on the Expression of γ-aminobutyric Acid B2 Receptor in Primary Cultured Rat Hippocampus Neurons%舒郁胶囊含药血清对大鼠海马神经元γ氨基丁酸B2受体蛋白表达的影响

    Institute of Scientific and Technical Information of China (English)

    姜英凤; 高杰; 魏盛; 薛玲; 葛庆芳

    2012-01-01

    Objective: Our aim was to investigate the protein changes of the expression of γ-aminobutyric acid B2 (GABABR2) receptor in primary cultured rat hippocampus neurons, to explore the intervention mechanism of Shuyu capsule for treating depression emotion preliminarily. Method; We used the chronic mild stress (CMS) to establish the depression emotion ( DE) model in rats, and then the rats were evaluated by sucrose intake, the body weight and open-field from beginning to the end for the model. Serum of rats in each group was collected and then added into the medium of vitro cultured hippocampus primary neurons. At last the expression of "y-aminobutyric acid B2 receptor was detected with Western blot respectively. Result: Compared with the normal group, the weight, the total score of open field test and the sucrose intake of preference test of rats in depression emotion model group lessened significantly (P <0. 01 ) . On the other hand, compared with the depression emotion model group, the weight, the total score of open field test and the sucrose intake of preference test of rats in Shuyu capsule , bupleurum and fluoxetine treatment groups increased significantly ( P < 0. 05 or P < 0. 01 ). Western blot demonstrated that the serum of model group rats obviously increased the protein levels of GABABR2 (P <0. 01 ) , compared with the normal control group. While serum of the Shuyu capsule and fluoxetine treatment groups markedly decreased the protein levels of GABABR2 (P <0. 05) , the bupleurum group had no difference with the model group, but the trendhad improved. Conclusion; The serum of rats with depression emotion could induce the high expression of GABABR2, the Shuyu capsule may play antidepressants by reducing the expression of GABABR2 in primary cultured rat hippocampus neurons. The bupleurum also has a good antidepressant effect, but the effect is less than Shuyu capsule.%目的:观察抑郁情绪大鼠模型给药血清对离体海马神经元γ氨基丁酸B2

  1. PKA and Epac cooperate to augment bradykinin-induced interleukin-8 release from human airway smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Halayko Andrew J

    2009-09-01

    Full Text Available Abstract Background Airway smooth muscle contributes to the pathogenesis of pulmonary diseases by secreting inflammatory mediators such as interleukin-8 (IL-8. IL-8 production is in part regulated via activation of Gq-and Gs-coupled receptors. Here we study the role of the cyclic AMP (cAMP effectors protein kinase A (PKA and exchange proteins directly activated by cAMP (Epac1 and Epac2 in the bradykinin-induced IL-8 release from a human airway smooth muscle cell line and the underlying molecular mechanisms of this response. Methods IL-8 release was assessed via ELISA under basal condition and after stimulation with bradykinin alone or in combination with fenoterol, the Epac activators 8-pCPT-2'-O-Me-cAMP and Sp-8-pCPT-2'-O-Me-cAMPS, the PKA activator 6-Bnz-cAMP and the cGMP analog 8-pCPT-2'-O-Me-cGMP. Where indicated, cells were pre-incubated with the pharmacological inhibitors Clostridium difficile toxin B-1470 (GTPases, U0126 (extracellular signal-regulated kinases ERK1/2 and Rp-8-CPT-cAMPS (PKA. The specificity of the cyclic nucleotide analogs was confirmed by measuring phosphorylation of the PKA substrate vasodilator-stimulated phosphoprotein. GTP-loading of Rap1 and Rap2 was evaluated via pull-down technique. Expression of Rap1, Rap2, Epac1 and Epac2 was assessed via western blot. Downregulation of Epac protein expression was achieved by siRNA. Unpaired or paired two-tailed Student's t test was used. Results The β2-agonist fenoterol augmented release of IL-8 by bradykinin. The PKA activator 6-Bnz-cAMP and the Epac activator 8-pCPT-2'-O-Me-cAMP significantly increased bradykinin-induced IL-8 release. The hydrolysis-resistant Epac activator Sp-8-pCPT-2'-O-Me-cAMPS mimicked the effects of 8-pCPT-2'-O-Me-cAMP, whereas the negative control 8-pCPT-2'-O-Me-cGMP did not. Fenoterol, forskolin and 6-Bnz-cAMP induced VASP phosphorylation, which was diminished by the PKA inhibitor Rp-8-CPT-cAMPS. 6-Bnz-cAMP and 8-pCPT-2'-O-Me-cAMP induced GTP

  2. Comparative effects of immediate-release and extended-release aspirin on basal and bradykinin-stimulated excretion of thromboxane and prostacyclin metabolites.

    Science.gov (United States)

    Gamboa, Jorge L; Devin, Jessica K; Ramirez, Claudia E; Yu, Chang; Nian, Hui; Lee, Rhonda H; Brown, Nancy J

    2016-04-01

    A goal of aspirin therapy is to inhibit thromboxane production and platelet aggregation without inhibiting endothelial production of the vasodilator and anti-thrombotic prostacyclin. This study tested the hypothesis that extended-release aspirin (NHP-554C) would have increased selectivity for inhibition of basal and simulated thromboxane formation compared to immediate-release aspirin (ASA). Thirty-six healthy subjects were randomized to NHP-554C or ASA groups. Within each group, subjects were randomized to 5-day treatment with 81 mg/d, 162.5 mg/d and placebo in a crossover design in which treatment periods were separated by 2-week washout. On the fifth day of treatment, 81 mg/d and 162.5 mg/d ASA reduced basal urinary excretion of the stable thromboxane metabolite 11-dehydro-thromboxane B2 62.3% and 66.2% and basal excretion of the stable prostacyclin metabolite 2,3-dinor-6-keto-PGF1α 22.8% and 26.5%, respectively, compared to placebo. NHP-554C 81 mg/d and 162.5 mg/d reduced 11-dehydro-thromboxane B2 53% (P = 0.03 vs. ASA 81 mg/d) and 67.9% and 2,3-dinor-6-keto-PGF1α 13.4% and 18.5%, respectively. NHP-554C 81 mg/d did not significantly reduce basal excretion of the prostacyclin metabolite. Both doses of ASA and NHP significantly reduced excretion of both thromboxane and prostacyclin metabolites following intravenous bradykinin. During NHP-554C 162.5 mg/d, but not during ASA, bradykinin significantly increased urinary 2,3-dinor-6-keto-PGF1α. Nevertheless, 11-dehydro-thromboxane B2 and 2,3-dinor-6-keto-PGF1α responses to bradykinin were statistically similar during ASA and NHP-554C. In conclusion, at doses of 81 and 162.5 mg/d immediate- and extended-release aspirin selectively decrease basal thromboxane production. Both forms of aspirin decrease bradykinin-stimulated thromboxane and prostacyclin production, but some stimulated prostacyclin production remains during treatment with NHP-554C. PMID:27069632

  3. Outcome of Venom Bradykinin Potentiating Factor on Renin Angiotensin System in Irradiated Rats

    International Nuclear Information System (INIS)

    Scorpion Venom contains a strong bradykinin potentiating factor (BPF) exhibiting angiotensin converting enzyme inhibition (ACEI). Irradiation and stimulation of renin-angiotensin system (RAS) induce oxidative stress. Interruption of the RAS by an ACEI or angiotensin II receptor blocker (ARB) losartan (LOS) and/or gamma-rays (4 Gy) were evaluated. Rats received 6 doses of BPF (1μg/g body wt) or of LOS (5 μg/g body wt). Treatment with BPF induced significant elevation in the level of potassium (K) and significant drop in the level of sodium (Na) and uric acid. Treatment with LOS significantly depressed the level of Na and uric acid compared to control. Irradiation discerned a significant elevation in malondialdehyde (MDA), advanced oxidative protein product (AOPP), aldosterone, Na, urea and creatinine, and a significant drop in the haematological values, glutathione (GSH), calcium (Ca) and uric acid. A significant decrease in MDA, aldosterone, urea, creatinine and uric acid compared to irradiated group was observed in irradiated treated groups. Irradiated animals treated with LOS showed a significant decrease in Na and chloride (Cl) compared to the irradiated group. Considerable amelioration of radiation-induced depression in haematopoiesis, improvement of oxidative stress and kidney function by BPF as ACEI or LOS as ARB are detected. Results add further identification to the properties of BPF

  4. Flotillins as regulators of ErbB2 levels in breast cancer

    DEFF Research Database (Denmark)

    Pust, S; Klokk, T I; Musa, N;

    2013-01-01

    Amplification and overexpression of the receptor tyrosine kinase ErbB2 occur in up to 30% of human breast cancers, and high ErbB2 levels are correlated with poor prognosis for breast cancer patients. In contrast to the epithelial growth factor receptor (ErbB1), ErbB2 is not downregulated by ligand...... complex with ErbB2 and Hsp90. The depletion of one of these proteins results in disruption of this complex, followed by destabilization of ErbB2 at the membrane, and its internalization and degradation. As a consequence, ErbB2-triggered downstream signalling is inhibited. Our data demonstrate a novel...

  5. Effect of Montelukast on bradykinin-induced contraction of isolated tracheal smooth muscle of guinea pig

    OpenAIRE

    Noor, A.; Najmi, M.H.; Bukhtiar, S.

    2011-01-01

    Aim: To explore the effect of montelukast on bradykinin-induced tracheal smooth muscle contraction of isolated guinea pig trachea. Study Design: To study the effect of bradykinin in the absence and in the presence of montelukast on the isolated tracheal smooth muscle of a guinea pig pretreated with indomethacin (10 -6 M), phentolamine (10 -5 M), and propranalol (10 -6 M), to eliminate the effect of endogenous prostaglandins and catecholamines. The trachealis smooth muscle activity was re...

  6. Formoterol and salbutamol inhibit bradykinin- and histamine-induced airway microvascular leakage in guinea-pig.

    OpenAIRE

    Advenier, C; Qian, Y.; Koune, J. D.; Molimard, M; Candenas, M. L.; Naline, E.

    1992-01-01

    1. The effects of the beta 2-adrenoceptor agonists, salbutamol and formoterol, on the increase of microvascular permeability induced by histamine or bradykinin in guinea-pig airways have been studied in vivo. Extravasation of intravenously injected Evans blue dye was used as an index of permeability. The effects of salbutamol and formoterol on the increase in pulmonary airway resistance induced by histamine or bradykinin have also been studied. 2. The increase in pulmonary airway resistance i...

  7. Effects of angiotensin-converting enzyme inhibition and bradykinin peptides in rats with myocardial infarction

    OpenAIRE

    Qu, Zhe; Xu, Hongxin; Tian, Yihao

    2015-01-01

    Background and objective: Angiotensin-converting enzyme (ACE) inhibitors have been reported to decrease myocardial remodeling and faciliate cardiac function improvement in the setting myocardial infarction by affecting bradykinin. The purpose of this study was to evaluate the combination effects of perindopril and bradykinin (BK) in rats with myocardial infarction. Methods: Wistar Rats underwent to left anterior descending (LAD) coronary artery ligation were allocated into MI group (n = 6); P...

  8. Bradykinin stimulation of nitric oxide production is not sufficient for gamma-globin induction

    Directory of Open Access Journals (Sweden)

    Čokić Vladan P.

    2014-01-01

    Full Text Available Introduction. Hydroxycarbamide, used in therapy of hemoglobinopathies, enhances nitric oxide (NO production both in primary human umbilical vein endothelial cells (HUVECs and human bone marrow endothelial cell line (TrHBMEC. Moreover, NO increases γ-globin and fetal hemoglobin levels in human erythroid progenitors. Objective. In order to find out whether simple physiologic stimulation of NO production by components of hematopoietic microenvironment can increase γ-globin gene expression, the effects of NO-inducer bradykinin were examined in endothelial cells. Methods. The study was performed in co-cultures of human erythroid progenitors, TrHBMEC and HUVECs by ozone-based chemiluminescent determination of NO and real-time quantitative RT-PCR. Results. In accordance with previous reports, the endogenous factor bradykinin increased endothelial cell production of NO in a dose- and time-dependent manner (0.1-0.6 μM up to 30 minutes. This induction of NO in HUVECs and TrHBMEC by bradykinin was blocked by competitive inhibitors of NO synthase (NOS, demonstrating NOS-dependence. It has been shown that bradykinin significantly reduced endothelial NOS (eNOS mRNA level and eNOS/Я-actin ratio in HUVEC (by twofold. In addition, bradykinin failed to increase γ-globin mRNA expression in erythroid progenitors only, as well as in co-culture studies of erythroid progenitors with TrHBMEC and HUVEC after 24 hours of treatment. Furthermore, bradykinin did not induce γ/β globin ratio in erythroid progenitors in co-cultures with HUVEC. Conclusion. Bradykinin mediated eNOS activation leads to short time and low NO production in endothelial cells, insufficient to induce γ-globin gene expression. These results emphasized the significance of elevated and extended NO production in augmentation of γ-globin gene expression. [Projekat Ministarstva nauke Republike Srbije, br. 175053

  9. Developmental acceleration of bradykinin-dependent relaxation by prenatal chronic hypoxia impedes normal development after birth.

    Science.gov (United States)

    Blum-Johnston, Carla; Thorpe, Richard B; Wee, Chelsea; Romero, Monica; Brunelle, Alexander; Blood, Quintin; Wilson, Rachael; Blood, Arlin B; Francis, Michael; Taylor, Mark S; Longo, Lawrence D; Pearce, William J; Wilson, Sean M

    2016-02-01

    Bradykinin-induced activation of the pulmonary endothelium triggers nitric oxide production and other signals that cause vasorelaxation, including stimulation of large-conductance Ca(2+)-activated K(+) (BKCa) channels in myocytes that hyperpolarize the plasma membrane and decrease intracellular Ca(2+). Intrauterine chronic hypoxia (CH) may reduce vasorelaxation in the fetal-to-newborn transition and contribute to pulmonary hypertension of the newborn. Thus we examined the effects of maturation and CH on the role of BKCa channels during bradykinin-induced vasorelaxation by examining endothelial Ca(2+) signals, wire myography, and Western immunoblots on pulmonary arteries isolated from near-term fetal (∼ 140 days gestation) and newborn, 10- to 20-day-old, sheep that lived in normoxia at 700 m or in CH at high altitude (3,801 m) for >100 days. CH enhanced bradykinin-induced relaxation of fetal vessels but decreased relaxation in newborns. Endothelial Ca(2+) responses decreased with maturation but increased with CH. Bradykinin-dependent relaxation was sensitive to 100 μM nitro-L-arginine methyl ester or 10 μM 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, supporting roles for endothelial nitric oxide synthase and soluble guanylate cyclase activation. Indomethacin blocked relaxation in CH vessels, suggesting upregulation of PLA2 pathways. BKCa channel inhibition with 1 mM tetraethylammonium reduced bradykinin-induced vasorelaxation in the normoxic newborn and fetal CH vessels. Maturation reduced whole cell BKCa channel α1-subunit expression but increased β1-subunit expression. These results suggest that CH amplifies the contribution of BKCa channels to bradykinin-induced vasorelaxation in fetal sheep but stunts further development of this vasodilatory pathway in newborns. This involves complex changes in multiple components of the bradykinin-signaling axes. PMID:26637638

  10. Further Identification of the Effect of Bradykinin Potentiating Factor Isolated From Scorpion Venom on Irradiated White Rat

    International Nuclear Information System (INIS)

    Scorpion venom of Androctonus amoreuxi contains a strong bradykinin potentiating factor (BPF) that augments bradykinin effect through enhancing its release and acts as an angiotensin converting enzyme inhibitor (ACEI). Both irradiation and stimulation of renin-angiotensin system (RAS) induce oxidative stress. Possible interruption of the RAS with an ACEI induced by BPF isolated from the scorpion, Androctonus amoreuxi venom or the presence of angiotensin II receptor blocker (ARB) losartan and/or γ- radiation were evaluated. The examined parameters included blood erythrocytes count (RBC), total leucocytic count (WBC), haemoglobin content (Hb) and hematocrit value (Hct) as well as, glutathione content (GSH), malondialdehyde (MDA) and advanced oxidative protein product (AOPP) of kidney homogenate besides aldosterone, sodium, potassium, chloride, calcium, urea, creatinine and uric acid levels of serum. A group of rats (70 - 80 gm each) were received i.p. injection of BPIF (1μg / g body wt) twice per week for three weeks, while the other group received i.p. injection of losartan (5μg / g body wt) twice per week for three weeks. γ-Irradiation was performed at a dose level of 4Gy. All animals were examined after an investigation period of 21 days from γ- irradiation. Either BPF or losartan was performed together with irradiation. The results pointed out that irradiation discerned a significant elevation in the level of MDA, AOPP, aldosterone, sodium, urea and creatinine, and a significant drop in the haematological values (RBCs, WBCs, Hb and Hct), GSH, calcium and uric acid. Repeated injections of BPF or losartan had a beneficial result against the deleterious effect of γ- irradiation. The present investigation clarifies comparable effects for treatment of radiation damage to the kidney through RAS by BPF as (ACEI) and losartan as (ARB). The present work adds further identification to the properties of BPF in controlling of radiation damage. Therapeutic agents from

  11. B2-B2.5 code benchmarking

    Energy Technology Data Exchange (ETDEWEB)

    Dekeyser, W.; Baelmans, M; Voskoboynikov, S.; Rozhansky, V.; Reiter, D.; Wiesen, S.; Kotov, V.; Boerner, P.

    2011-01-15

    ITER-IO currently (and since about 15 years) employs the SOLPS4.xxx code for its divertor design, currently version SOLPS4.3. SOLPS.xxx is a special variant of the B2-EIRENE code, which was originally developed by an European consortium (FZ Juelich, AEA Culham, ERM Belgium/KU Leuven) in the late eighties and early nineties of the last century under NET contracts. Until today even the very similar edge plasma codes within the SOLPS family, if run on a seemingly identical choice of physical parameters, still sometimes disagree significantly with each other. It is obvious that in computational engineering applications, as they are carried out for the various ITER divertor aspects with SOLPS4.3 for more than a decade now, any transition from one to another code must be fully backward compatible, or, at least, the origin of differences in the results must be identified and fully understood quantitatively. In this report we document efforts undertaken in 2010 to ultimately eliminate the third issue. For the kinetic EIRENE part within SOLPS this backward compatibility (back until 1996) was basically achieved (V. Kotov, 2004-2006) and SOLPS4.3 is now essentially up to date with the current EIRENE master maintained at FZ Juelich. In order to achieve a similar level of reproducibility for the plasma fluid (B2, B2.5) part, we follow a similar strategy, which is quite distinct from the previous SOLPS benchmark attempts: the codes are ''disintegrated'' and pieces of it are run on smallest (i.e. simplest) problems. Only after full quantitative understanding is achieved, the code model is enlarged, integrated, piece by piece again, until, hopefully, a fully backward compatible B2 / B2.5 ITER edge plasma simulation will be achieved. The status of this code dis-integration effort and its findings until now (Nov. 2010) are documented in the present technical note. This work was initiated in a small workshop by the three partner teams of KU Leuven, St. Petersburg

  12. 汉族人群中血管紧张素转换酶抑制剂所致咳嗽与血管紧张素转换酶基因及缓激肽β2受体基因多态性的关系%The Association between ACE Inhibitor (ACEI)-Induced Cough and the Polymorphism of Angiotensin Converting Enzyme (ACE) Gene and Bradykinin β2 Receptor(BDKRB2) Gene in Han Nationality

    Institute of Scientific and Technical Information of China (English)

    王刚; 杨军; 唐振旺; 宁国庆; 曹燕; 万娟

    2012-01-01

    Objective: To investigate the association between angiotensin converting enzyme inhibitor (ACEI)-induced cough and the polymorphism of angiotensin converting enzyme (ACE) gene and bradykinin ($2 receptor (BDKRB2) gene in Han nationality. Methods: Polymerase chain reaction (PCR) was used to examine ACE I/D and BDKRB2 CT polymorphism in 151 ACEI-induced cough subjects and 151 no cough subjects in Han population. And UV-method was used to detect the ACE activity. Results:ACE gene distribution in the cough group: type II was 47.0%, ID genotype was 42.4%, DD genotype was 10.6%; Non-cough group were 39.7%, 47.0%, 13.3% respectively, and there was statistically significant difference between the two groups(P 0.05); The level of ACE activity in the Cough group [(28.3 ± 10.1) U / L,] was significantly lower than non-cough group [(40.2 ± 9.4) U / L,(P <0.01).]. Conclusions: For han population, ACEI-induced cough related to ACE gene polymorphism and serum ACE activity, and there was no statistically significant association between BDKRB2 C / T and cough.%目的:探讨汉族人群中血管紧张素转换酶抑制剂(ACEI)所致咳嗽与血管紧张素转换酶(ACE)基因及缓激肽β2受体(BDKRB2)基因多态性的关系.方法:应用聚合酶链反应(PCR)方法,检测汉族人群中151例由于服用ACEI引起的咳嗽患者及151例未发生咳嗽的患者的ACEI/D及BDKRB2C/T的多态性,并采用紫外法检测ACE活性.结果:发现ACE基因分布在咳嗽组中Ⅱ型为47.0%,ID型为42.4%,DD型为10.6%;无咳嗽组分别为39.7%、47.0%、13.3%,两组相比其差异具有统计学意义(P<0.01);BDKRB2基因分布在咳嗽组中CC型为21.3%,CT型为50.0%,TT型为28.7%,无咳嗽组分别为22.5%、47.7%、29.8%,两组相比其差异无统计学意义(P>0.05);咳嗽组ACE活性水平为[(28.3±10.1)U/L]明显低于无咳嗽组[(40.2± 9.4)U/L],两组相比其差异具有统计学意义(P<0.01).结论:汉族人群中ACEI所致咳嗽

  13. The effect of an angiotensin converting enzyme inhibitor, ramipril, on bronchial responses to inhaled histamine and bradykinin in asthmatic subjects.

    OpenAIRE

    Dixon, C M; Fuller, R W; Barnes, P J

    1987-01-01

    The effect of a potent inhibitor of angiotensin-converting enzyme, ramipril, was studied on both inhaled histamine and bradykinin-induced bronchoconstriction in six male, normotensive, mild asthmatic subjects. Oral administration of 10 mg ramipril caused no change in lung function or airway reactivity to inhaled histamine or bradykinin despite achieving adequate reduction in angiotensin-converting enzyme activity.

  14. Neurophysiological mechanisms of bradykinin-evokedmucosal chloride secretion in guinea pig small intestine

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    AIM To investigate the mechanism for bradykinin(BK) to stimulate intestinal secretomotor neurons andintestinal chloride secretion.METHODS: Muscle-stripped guinea pig ileal preparationswere mounted in Ussing flux chambers for therecording of short-circuit current (Isc ). Basal Isc andIsc stimulated by BK when preincubated with the BKreceptors antagonist and other chemicals were recordedusing the Ussing chamber system. Prostaglandin E2(PGE2) production in the intestine was determined byenzyme immunologic assay (EIA).RESULTS: Application of BK or B2 receptorB2R) agonistsignificantly increased the baseline Isc compared to thecontrol. B2R antagonist, tetrodotoxin and scopolamine(blockade of muscarinic receptors) significantly suppressedthe increase in Isc evoked by BK. The BK-evokedIsc was suppressed by cyclooxygenase (COX)-1 or COX-2specific inhibitor as well as nonselective COX inhibitors.Preincubation of submucosa/mucosa preparations withBK for 10 min significantly increased PGE2 production andthis was abolished by the COX-1 and COX-2 inhibitors.The BK-evoked Isc was suppressed by nonselective EPreceptors and EP4 receptor antagonists, but selective EP1receptor antagonist did not have a significant effect onthe BK-evoked Isc . Inhibitors of PLC, PKC, calmodulin orCaMKⅡ failed to suppress BK-induced PGE2 production.CONCLUSION: The results suggest that BK stimulatesneurogenic chloride secretion in the guinea pig ileumby activating B2R, through COX increasing PGE2 production.The post-receptor transduction cascade includesactivation of PLC, PKC, CaMK, IP3 and MAPK.

  15. Potentiation of bradykinin action on smooth muscle by a scorpion venom extract.

    Science.gov (United States)

    Araujo, R L; Gomez, M V

    1976-08-01

    Gel filtration of the water extract of the venom of the scorpion T. serrulatus showed four peaks; the first peak (P1) is devoid of toxic activity but increases the bradykinin-induced contraction of isolated rat uterus and guinea-pig ileum. The stepwise fractionation of the pooled P1 peak was performed in a DEAE-cellulose column and the bradykinin potentiating activity was found in the second protein peak. Finger-printing of this material showed that the bradykinin potentiating material migrates to the anode, giving two spots when submitted to chromatography, the activity being found in the spot that presents the greatest Rf. The potentiator is destroyed by heating at 97 degrees C, is not dialysable and is destroyed by incubation with pronase. Some of these properties differentiate it from the BPF's from snake venoms. PMID:976731

  16. The Mysterious Ways of ErbB2/HER2 Trafficking

    OpenAIRE

    Vibeke Bertelsen; Espen Stang

    2014-01-01

    The EGFR- or ErbB-family of receptor tyrosine kinases consists of EGFR/ErbB1, ErbB2/HER2, ErbB3/HER3 and ErbB4/HER4. Receptor activation and downstream signaling are generally initiated upon ligand-induced receptor homo- or heterodimerization at the plasma membrane, and endocytosis and intracellular membrane transport are crucial for regulation of the signaling outcome. Among the receptors, ErbB2 is special in several ways. Unlike the others, ErbB2 has no known ligand, but is still the favore...

  17. [Treatment of drugs-associated non-hereditary angioedema mediated by bradykinin].

    Science.gov (United States)

    Muller, Yannick; Harr, Thomas

    2016-01-13

    Angioedema is a deep intradermal or sub-cutaneous edema, which can be mediated by histamine, bradykinin or mixture of both components. The aims of this review are to describe the clinical approach and diagnosis of non-hereditary bradykinin-mediated angioedema induced by drugs such as: angiotensin-converting inhibitor, sartan, gliptins, rapamycin or some thrombolytic reagents and renin inhibitors. Furthermore, we will discuss the drug management of these angioedema, which is mainly based on C1 inhibitor concentrate or icatibant administration. PMID:26946694

  18. Marketing Optimization for B2B Market

    OpenAIRE

    Kaynova Tatyana V.

    2012-01-01

    The article presents market definition B2B, the necessity to optimize marketing B2B market, provides a system for B2B-marketing and developed stages of its formation. On this basis it was identified key factors of customer loyalty and are the stages of development of loyalty programs for customers market B2B.

  19. A new therapeutic antibody masks ErbB2 to its partners.

    Science.gov (United States)

    Badache, Ali; Hynes, Nancy E

    2004-04-01

    In cancer cells, the ErbB2 receptor tyrosine kinase can be activated in two ways: by overexpression or by ligand-mediated stimulation of another ErbB receptor. The ErbB2-targeting antibody trastuzumab (Herceptin) is used for treatment of metastatic breast cancer patients whose tumors overexpress ErbB2. A new structural study in this issue of Cancer Cell reveals how targeting ErbB2 with another antibody, pertuzumab (Omnitarg), prevents ligand-induced dimerization of ErbB2 with the other ErbB receptors. Pertuzumab's novel mode of action might offer additional therapeutic opportunities for treatment of tumors expressing ligand-activated ErbB2. PMID:15093533

  20. Genetic Polymorphisms in the EGFR (R521K and Estrogen Receptor (T594T Genes, EGFR and ErbB-2 Protein Expression, and Breast Cancer Risk in Tunisia

    Directory of Open Access Journals (Sweden)

    Imen Kallel

    2009-01-01

    Full Text Available We evaluated the association of epidermal growth factor receptor (EGFR 142285G>A (R521K and estrogen receptor alpha (ESR1 2014G>A (T594T single nucleotide polymorphisms with breast cancer risk and prognosis in Tunisian patients. EGFR 142285G>A and ESR1 2014G>A were genotyped in a sample of 148 Tunisian breast cancer patients and 303 controls using PCR-RFLP method. Immunohistochemitsry was used to evaluate the expression levels of EGFR, HER2, ESR1, progesterone receptor and BCL2 in tumors. We found no evidence for an association between EGFR R521K polymorphism and breast cancer risk. However, we found that the homozygous GG (Arg genotype was more prevalent in patients with lymph node metastasis (=.03 and high grade tumors (=.011. The ESR1 2014G allele showed significant association with breast cancer risk (=.025. The GG genotype was associated with HER2 overexpression and this association withstood univariate and multivariate analyses (=.009; =.021, resp.. These data suggest that the R521K might be a prognostic factor, because it correlates with both tumor grade and nodule status. The higher expression of HER2 in ESR1 T594T GG patients suggests the possibility that ESR1 gene polymorphisms accompanied by HER2 expression might influence the pathogenesis of breast cancers.

  1. Effects of the bradykinin antagonist B4310 on smooth muscles and blood pressure in the rat, and its enzymatic degradation.

    OpenAIRE

    Griesbacher, T; Lembeck, F.; Saria, A.

    1989-01-01

    1. Six competitive bradykinin (Bk) antagonists were tested for their agonistic properties on the rat uterus. Five of these peptides showed agonistic effects only at concentrations at least two orders of magnitude higher than those of bradykinin. 2. The antagonistic potency of Lys-Lys-3-Hyp-5,8-Thi-7-DPhe-Bk (B4310) in the rat uterus (pA2 = 7.24) and in the rat duodenum (pA2 = 7.31) was very similar to that determined in an earlier study for the antagonism of the bradykinin-induced stimulation...

  2. EphB2 in the Medial Prefrontal Cortex Regulates Vulnerability to Stress.

    Science.gov (United States)

    Zhang, Ruo-Xi; Han, Ying; Chen, Chen; Xu, Ling-Zhi; Li, Jia-Li; Chen, Na; Sun, Cheng-Yu; Chen, Wen-Hao; Zhu, Wei-Li; Shi, Jie; Lu, Lin

    2016-09-01

    The ephrin B2 (EphB2) receptor is a tyrosine kinase receptor that is associated with synaptic development and maturation. It has recently been implicated in cognitive deficits and anxiety. However, still unknown is the involvement of EphB2 in the vulnerability to stress. In the present study, we observed decreases in EphB2 levels and their downstream molecules in the medial prefrontal cortex (mPFC) but not in the orbitofrontal cortex (OFC) in mice that were susceptible to chronic social defeat stress. The activation of EphB2 receptors with EphrinB1-Fc in the mPFC produced stress-resistant and antidepressant-like behavioral effects in susceptible mice that lasted for at least 10 days. EphB2 receptor knockdown by short-hairpin RNA in the mPFC increased the susceptibility to stress and induced depressive-like behaviors in a subthreshold chronic social defeat stress paradigm. These behavioral effects were associated with changes in the phosphorylation of cofilin and membrane α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) trafficking and the expression of some synaptic proteins in the mPFC. We also found that EphB2 regulated stress-induced spine remodeling in the mPFC. Altogether, these results indicate that EphB2 is a critical regulator of stress vulnerability and might be a potential target for the treatment of depression. PMID:27103064

  3. 38 CFR 18b.2 - Reviewing authority.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Reviewing authority. 18b.2 Section 18b.2 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS (CONTINUED... Rules § 18b.2 Reviewing authority. The term reviewing authority means the Secretary of Veterans...

  4. Epidermal growth factor, bradykinin, and histamine stimulate inositol phosphate formation in A431 human epidermoid carcinoma cells

    International Nuclear Information System (INIS)

    Incubation of A431 cells with epidermal growth factor (EGF), bradykinin (BK), or histamine (HA) resulted in a 3-, 6-, or 3-fold increase, respectively, in the formation of the inositol phosphates (InsP), InsP1, and InsP2, and InsP3. The K/sub 0.5/ values for stimulation were 3 nM, 3 nM, and 10 μM for EGF, BK, and HA, respectively. Total InsP formation was essentially linear for each hormone for at least 10 min; the accumulation of InsP3 was maximal within 15 sec. The efflux of 45Ca++ from 45Ca-preincubated cells was increased by all three hormones, suggesting that EGF-, BK-, and HA-stimulated breakdown of phosphoinositides results in Ca++ mobilization in these cells. A431 cells should prove a useful model system for comparison of the mechanism(s) whereby EGF and other hormone receptors regulate phosphoinositide metabolism

  5. Clinical relevance of ErbB-2/HER2 nuclear expression in breast cancer

    International Nuclear Information System (INIS)

    The biological relevance of nuclear ErbB-2/HER2 (NuclErbB-2) presence in breast tumors remains unexplored. In this study we assessed the clinical significance of ErbB-2 nuclear localization in primary invasive breast cancer. The reporting recommendations for tumor marker prognostic studies (REMARK) guidelines were used as reference. Tissue microarrays from a cohort of 273 primary invasive breast carcinomas from women living in Chile, a Latin American country, were examined for membrane (MembErbB-2) and NuclErbB-2 expression by an immunofluorescence (IF) protocol we developed. ErbB-2 expression was also evaluated by immunohistochemistry (IHC) with a series of antibodies. Correlation between NuclErbB-2 and MembErbB-2, and between NuclErbB-2 and clinicopathological characteristics of tumors was studied. The prognostic value of NuclErbB-2 in overall survival (OS) was evaluated using Kaplan-Meier method, and Cox model was used to explore NuclErbB-2 as independent prognostic factor for OS. The IF protocol we developed showed significantly higher sensitivity for detection of NuclErbB-2 than IHC procedures, while its specificity and sensitivity to detect MembErbB-2 were comparable to those of IHC procedures. We found 33.6% NuclErbB-2 positivity, 14.2% MembErbB-2 overexpression by IF, and 13.0% MembErbB-2 prevalence by IHC in our cohort. We identified NuclErbB-2 positivity as a significant independent predictor of worse OS in patients with MembErbB-2 overexpression. NuclErbB-2 was also a biomarker of lower OS in tumors that overexpress MembErbB-2 and lack steroid hormone receptors. We revealed a novel role for NuclErbB-2 as an independent prognostic factor of poor clinical outcome in MembErbB-2-positive breast tumors. Our work indicates that patients presenting NuclErbB-2 may need new therapeutic strategies involving specific blockage of ErbB-2 nuclear migration

  6. Isolation and characterization of Bradykinin potentiating peptides from Agkistrodon bilineatus venom

    OpenAIRE

    Munawar, Aisha; Zahid, Anum; Negm, Amr; Akrem, Ahmed; Spencer, Patrick; Betzel, Christian

    2016-01-01

    Background Snake venom is a source of many pharmacologically important molecules. Agkistrodon bilineatus commonly known as Cantil, is spread over Central America particularly in Mexico and Costa Rica. From the venom of Agkistrodon bilineatus we have isolated and characterised six hypotensive peptides, and two bradykinin inhibitor peptides. The IC-50 value of four synthesized peptides was studied, towards angiotensin converting enzyme, in order to study the structure-function relationship of t...

  7. NCBI nr-aa BLAST: CBRC-PHAM-01-1757 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-PHAM-01-1757 ref|NP_001003095.1| bradykinin receptor B2 [Canis lupus familiari...s] gb|AAK21217.1|AF334948_1 B2 bradykinin receptor [Canis lupus familiaris] NP_001003095.1 0.0 80% ...

  8. Sintering of TiB2 ceramics

    Directory of Open Access Journals (Sweden)

    M. Swiatek

    2007-11-01

    Full Text Available Purpose: Titanium diborides (TiB2 ceramic is particularly interesting because it exhibits high elastic modulus and hardness as well as high thermal conductivity. The interest in TiB2 ceramic increased enormously due to these properties but applications seem to be limited due to difficulties during densification process. In the experiment the TiB2 compacts was obtained using HP-HT method. The aim of this study is to work out and optimize the sintering densification process of TiB2 ceramics.Design/methodology/approach: The high temperature-high pressure (HT-HP Bridgman type apparatus was used for densification method of TiB2 powder. Ceramics were sintered at pressure of 7.2 ± 0.2 GPa and temperature at 1500-2300ºC ± 50ºC. The duration of sintering was 60 seconds. In order to investigate the structure changes, the optical and scanning electron microscope was used. Mechanical properties were determined by Vickers hardness. Young modulus measurements were carried out using ultrasonic method.Findings: The TiB2 ceramics was obtained without using sintering agents. The properties and structure of TiB2 ceramics strongly depend on conditions of sintering process. The application of the temperature of 1500ºC±50ºC and pressure of 7.2 ± 0.2 GPa and time of 60 seconds permits to obtain the TiB2 ceramics without cracks.Practical implications: The TiB2 ceramic might be used for production of composites. From a practical position it is important to optimize the sintering densification of TiB2 ceramic.Originality/value: The TiB2 ceramics were formed using HP-HT technique without the use of additives. This method of sintering for TiB2 ceramics is original one.T7

  9. THE REINFORCING MECHANISM OF TiB2 IN TiB2/A357 COMPOSITE

    Institute of Scientific and Technical Information of China (English)

    B. Yu; Y.J. Zhang; Z.X. Zhao; F.X. Zhao; Q.K. Cai; C.S. Liu

    2003-01-01

    Mechanical properties were tested for in situ TiB2/A357 composite fabricated by LSM (mixed salts reaction) method. Microstructures of as cast and plastic deformed TiB2/A357 were investigated. The results show that there is a low misfit between (200)A1 and (101)TiB2 with [011]Al // [101]TiB2. There is a change from fully dendritic structure of the α-Al of A357 to a rosette-type structure of TiB2/A357. Significant increases in proof stress and Young's modulus can be obtained at low TiB2 additions. There exist dislocation loops around neighboring TiB2 particles with about 0. 1ηm in diameter and dislocation multiplication near TiB2 particles.

  10. The inhibition of kallikrein-bradykinin pathway may be useful in the reduction of allergic reactions during honeybee venom immunotherapy

    Directory of Open Access Journals (Sweden)

    Ervin Ç. Mingomataj

    2009-05-01

    Full Text Available "nVenom immunotherapy (VIT protects patients with hymenoptera venom anaphylaxis from subsequent potentially life-threatening reactions. The most important side effects during VIT are systemic anaphylactic reactions (SAR, which are more prevalent during honeybee VIT. Despite the demonstrated diversity with regard to venom compounds, previous publications did not mention the plausible reason that can justify the difference of SAR frequency between honeybee and wasps. On the other hand, pre-treatment with H1-blocking antihistamines reduces the frequency and intensity of local and mild systemic anaphylactic reactions during VIT, but not appropriately moderate adverse reactions such as abdominal pain or angioedematous reactions, which can occur more prevalently also during honeybee VIT. In contrast to hymenoptera venom (HV anaphylaxis, these symptoms are very common during hereditary angioedema (HAE. In addition, in some patients who repeatedly experienced anaphylactic reactions during hyposensitization with HV are reported significantly lower renin, angiotensinogen I, and angiotensinogen II plasma levels. These facts may indicate that during honeybee VIT could be occurred a defective implication of renin-angiotensin system. This may be possible, because among hymenoptera, only the HV contains the antigen melittin, a potent kallikrein activator. These effects during honeybee VIT are similar to the HAE, because melittin-induced kallikrein activation on the first hand, as well as the implication of complement classical pathway during HAE on the second one, can lead both to increased bradykinin (BK secretion, plasma extravasation, and therefore to the occurrence of angioedema and abdominal symptoms. Consequently, the clinical effectiveness of BK receptor and generator blockers such as icatibant, ecallantide or NPC 18884, shown recently during the treatment of HAE attacks and acetic acid-induced abdominal constrictions in mice, may lead to the hypothesis

  11. Role of calcium-activated potassium channels with small conductance in bradykinin-induced vasodilation of porcine retinal arterioles

    DEFF Research Database (Denmark)

    Dalsgaard, Thomas; Kroigaard, Christel; Bek, Toke;

    2009-01-01

    PURPOSE: Endothelial dysfunction and impaired vasodilation may be involved in the pathogenesis of retinal vascular diseases. In the present study, the mechanisms underlying bradykinin vasodilation were examined and whether calcium-activated potassium channels of small (SK(Ca)) and intermediate (IK......(Ca)) conductance are involved in regulation of endothelium-dependent vasodilation in retinal arterioles was investigated. METHODS: Porcine retinal arterioles (diameter approximately 112 microm, N = 119) were mounted in microvascular myographs for isometric tension recordings. The arterioles were contracted with...... the thromboxane analogue, U46619, and concentration-response curves were constructed for bradykinin and a novel opener of SK(Ca) and IK(Ca) channels, NS309. RESULTS: In U46619-contracted arterioles, bradykinin and NS309 induced concentration-dependent relaxations. In vessels without endothelium...

  12. Hotelzon's B2B content marketing plan

    OpenAIRE

    Nguyen, Trang

    2015-01-01

    This thesis follows a research-based structure. The objective of this research was to help the case company Hotelzon develop a practical business-to-business (B2B) content marketing plan to engage new customers. The research topic came up when the case company named Hotelzon started expanding its business to many other countries. Therefore, attracting new prospects has become a critical issue to B2B corporates in this online world and constantly changing business environment. The first pa...

  13. A liver metalloendopeptidase which degrades the circulating hypotensive peptide hormones bradykinin and atrial natriuretic peptide

    Directory of Open Access Journals (Sweden)

    Carvalho K.M.

    1999-01-01

    Full Text Available A new metalloendopeptidase was purified to apparent homogeneity from a homogenate of normal human liver using successive steps of chromatography on DEAE-cellulose, hydroxyapatite and Sephacryl S-200. The purified enzyme hydrolyzed the Pro7-Phe8 bond of bradykinin and the Ser25-Tyr26 bond of atrial natriuretic peptide. No cleavage was produced in other peptide hormones such as vasopressin, oxytocin or Met- and Leu-enkephalin. This enzyme activity was inhibited by 1 mM divalent cation chelators such as EDTA, EGTA and o-phenanthroline and was insensitive to 1 µM phosphoramidon and captopril, specific inhibitors of neutral endopeptidase (EC 3.4.24.11 and angiotensin-converting enzyme (EC 3.4.15.1, respectively. With Mr 85 kDa, the enzyme exhibits optimal activity at pH 7.5. The high affinity of this endopeptidase for bradykinin (Km = 10 µM and for atrial natriuretic peptide (Km = 5 µM suggests that it may play a physiological role in the inactivation of these circulating hypotensive peptide hormones.

  14. Preubiquitinated chimeric ErbB2 is constitutively endocytosed and subsequently degraded in lysosomes

    Energy Technology Data Exchange (ETDEWEB)

    Vuong, Tram Thu [Institute of Clinical Medicine, University of Oslo, Rikshospitalet, 0027 Oslo (Norway); Berger, Christian [Department of Pathology, Oslo University Hospital, Rikshospitalet, P.O. Box 4950 Nydalen, 0424 Oslo (Norway); Bertelsen, Vibeke; Rødland, Marianne Skeie [Institute of Clinical Medicine, University of Oslo, Rikshospitalet, 0027 Oslo (Norway); Stang, Espen [Department of Pathology, Oslo University Hospital, Rikshospitalet, P.O. Box 4950 Nydalen, 0424 Oslo (Norway); Madshus, Inger Helene, E-mail: i.h.madshus@medisin.uio.no [Institute of Clinical Medicine, University of Oslo, Rikshospitalet, 0027 Oslo (Norway); Department of Pathology, Oslo University Hospital, Rikshospitalet, P.O. Box 4950 Nydalen, 0424 Oslo (Norway)

    2013-02-01

    The oncoprotein ErbB2 is endocytosis-deficient, probably due to its interaction with Heat shock protein 90. We previously demonstrated that clathrin-dependent endocytosis of ErbB2 is induced upon incubation of cells with Ansamycin derivatives, such as geldanamycin and its derivative 17-AAG. Furthermore, we have previously demonstrated that a preubiquitinated chimeric EGFR (EGFR-Ub{sub 4}) is constitutively endocytosed in a clathrin-dependent manner. We now demonstrate that also an ErbB2-Ub{sub 4} chimera is endocytosed constitutively and clathrin-dependently. Upon expression, the ErbB2-Ub{sub 4} was further ubiquitinated, and by Western blotting, we demonstrated the formation of both Lys48-linked and Lys63-linked polyubiquitin chains. ErbB2-Ub{sub 4} was constitutively internalized and eventually sorted to late endosomes and lysosomes where the fusion protein was degraded. ErbB2-Ub{sub 4} was not cleaved prior to internalization. Interestingly, over-expression of Ubiquitin Interaction Motif-containing dominant negative fragments of the clathrin adaptor proteins epsin1 and Eps15 negatively affected endocytosis of ErbB2. Altogether, this argues that ubiquitination is sufficient to induce clathrin-mediated endocytosis and lysosomal degradation of the otherwise plasma membrane localized ErbB2. Also, it appears that C-terminal cleavage is not required for endocytosis. -- Highlights: ► A chimera containing ErbB2 and a tetra-Ubiquitin chain internalizes constitutively. ► Receptor fragmentation is not required for endocytosis of ErbB2. ► Ubiquitination is sufficient to induce endocytosis and degradation of ErbB2. ► ErbB2-Ub4 is internalized clathrin-dependently.

  15. B2B Pioneer A Millionaire Maker

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    China should soon see its largest group of instant millionaires after Jack Ma,Chief Executive Officer and Chairman of Alibaba Group,announced on July 27 that the China’s preeminent e-commerce company has initiated the listing of its B2B unit alibaba.com

  16. B2-Eirene modelling of ASDEX Upgrade

    Science.gov (United States)

    Coster, D. P.; Schneider, R.; Neuhauser, J.; Bosch, H.-S.; Wunderlich, R.; Fuchs, C.; Mast, F.; Kallenbach, A.; Dux, R.; Becker, G.; Braams, B. J.; Reiter, D.; ASDEX Upgrade Team

    1997-02-01

    The extension of the computational region of the coupled fluid plasma, Monte-Carlo neutrals code, B2-Eirene, to the plasma center is discussed. The simulation of completely detached H-mode plasma is presented, as is the modelling of He and Ne compression.

  17. ER阳性乳腺癌PR亚型与C-erbB-2表达关系的研究%Association between progesterone receptor isoforms A and B and HER-2/neu expression in estrogen receptor-positive breast cancers

    Institute of Scientific and Technical Information of China (English)

    申郑堂; 郭旭辉; 黄俊辉; 刘少华; 罗沙阳; 陈飞宇

    2009-01-01

    目的 研究雌激素受体(ER)和孕激素受体(PR)阳性乳腺癌孕激素受体亚型(PR-A、PR-B)的表达,探讨PR-A、PR-B及其比值(PR-A/PR-B,A/B)与表皮生长因子受体-2(C-erbB-2,Her-2/neu)表达的关系及对无病生存期的影响.方法 选取该科2001年3月-2003年10月手术治疗ER、PR阳性乳腺癌65例,癌组织标本采用免疫组织化学SP法检测PR-A、PR-B表达状态,半定量法判定结果 .运用SPSS13.0统计软件包及X2检验进行结果 处理,Kaplan-Meier法描述生存曲线.结果 PR-A、PR-B阳性表达物住于细胞核中,细胞质及细胞膜无表达;乳腺癌孕激素受体亚型PR-A阳性表达占90.77%(59/65)、PR-B占58.46%(38/65)(P1的患者中,C-erbB-2阳性33例(84.62%),阴性6例(15.38%)(P1的患者无病生存期明显低于A/B值≤1的患者(P0.05).结论 在雌、孕激素受体阳性乳腺癌中,孕激素受体亚型PR-A表达高于PR-B表达,且A/B值增高(>1).在C-berB-2阳性表达的乳腺癌中,A/B值>1时临床预后差,预示对三苯氧胺治疗不敏感.

  18. Thermodynamic properties of vitamin B2

    International Nuclear Information System (INIS)

    Graphical abstract: - Highlights: • Temperature dependence of heat capacity of vitamin B2 has been measured by precision adiabatic vacuum calorimetry. • The thermodynamic functions of the vitamin B2 have been determined for the range from T → 0 to 322 K. • The energy of combustion of the riboflavin has been measured at 298.15 K. • The enthalpy of combustion ΔcH° and the thermodynamic parameters ΔfH°, ΔfS°, ΔfG° have been calculated. - Abstract: In the present work temperature dependence of heat capacity of vitamin B2 (riboflavin) has been measured for the first time in the range from 6 to 322 K by precision adiabatic vacuum calorimetry. Based on the experimental data, the thermodynamic functions of the vitamin B2, namely, the heat capacity, enthalpy H°(T) − H°(0), entropy S°(T) − S°(0) and Gibbs function G°(T) − H°(0) have been determined for the range from T → 0 to 322 K. The value of the fractal dimension D in the function of multifractal generalization of Debye's theory of the heat capacity of solids was estimated and the character of heterodynamics of structure was detected. In a calorimeter with a static bomb and an isothermal shield, the energy of combustion of the riboflavin has been measured at 298.15 K. The enthalpy of combustion ΔcH° and the thermodynamic parameters ΔfH°, ΔfS°, ΔfG° and of reaction of formation of the riboflavin from simple substances at T = 298.15 K and p = 0.1 MPa have been calculated

  19. Electronic structure of MgB2

    Indian Academy of Sciences (India)

    P Modak; R S Rao; B K Godwal; S K Sikka

    2002-05-01

    Results of ab initio electronic structure calculations on the compound MgB2 using the FPLAPW method employing GGA for the exchange-correlation energy are presented. Total energy minimization enables us to estimate the equilibrium volume, / ratio and the bulk modulus, all of which are in excellent agreement with experiment. We obtain the mass enhancement parameter by using our calculated (F) and the experimental specific heat data. The c is found to be 24.7 K.

  20. Tritium-bradykinin binding site localization in guinea pig urinary system

    International Nuclear Information System (INIS)

    Bradykinin (BK) causes vasodilation and increases free water and sodium excretion in the kidney and stimulates smooth muscle contraction in the ureter and bladder. Several proposed sites of action for BK include the renal medullary collecting duct, renal blood vessels and the ureter and bladder smooth muscle. This study employs 3H-BK autoradiography to localize the sites of BK action. 3H-BK binding sites in the kidney are localized in the medullary interstitium where BK may produce prostaglandins which mediate its blood flow, natriuretic and diuretic effects. 3H-BK binding sites in the ureter and bladder are localized in the lamina propria below the basal epithelial layer and absent over the muscle layers suggesting an indirect action on urinary tract smooth muscle

  1. Effect of TiB2 Pretreatment on Pt/TiB2 Catalyst Performance

    International Nuclear Information System (INIS)

    Highlights: • We pretreated Titanium diboride by different acids and alkali. • We synthesis the Pt/as-pretreated TiB2 catalysts by a colloid route. • We investigated the effects of TiB2 Pretreatment on Pt/TiB2 Catalyst Performance. • The BET surface area and defects on the surface have a close relationship with the deposition of Pt nanoparticles. - Abstract: Carbon support corrosion of traditional Pt/C catalyst is one of the major contributors causing poor durability of proton exchange membrane fuel cells (PEMFC). Titanium diboride (TiB2) has high electrical conductivity and considerable chemical stability, which making it as a good candidate for catalyst support in PEMFC. In this work, TiB2 was pretreated by different acid and alkali. The as-obtained samples were characterized by Ex-situ microscopy (ESM) and X-ray diffraction (XRD). The pore size distribution (PSD) was analyzed by using DFT method. The PSD shows distinct volume in mesopore regions (less than 50 nm). The TiB2 pretreated by H2O2 shows the biggest BET surface area of 57 m2 g−1 and its PSD focus on mesoporous (1.5-8 nm) region, which resulted to high dispersion and better loading of Pt particles. The Hydrogen oxidization reaction (HOR) and oxygen reduction reaction (ORR) activity was characterized by Rotating Disk Electrode (RDE). The Pt/TiB2 prepared by H2O2-pretreated TiB2 using the colloidal method showed better half-cell electrochemical performance. Facile synthetic for the development of Pt/TiB2 catalysts was developed

  2. MgB2 superconductors with addition of ZrB2 and different carbon sources

    International Nuclear Information System (INIS)

    MgB2 has been catching the attention due to the possibility to apply the material in magnets and electronic devices, operating with cryocoolers. In this work, MgB2 bulks were developed and analyzed with addition of ZrB2, another diboride with the same C32 hexagonal structure as MgB2, and simultaneous addition of different carbon sources (SiC, graphite, and carbon nanotubes). The objective of these additions is to modify the Mg planes with the diborides and to dope the material with carbon, improving the upper critical fields. Besides the doping of the material, this method creates crystalline defects in the superconducting matrix, which can act as pinning centers. As a result we could improve the critical current density of the material and estimate the behavior of dopants on the superconducting properties.

  3. Vascular endothelial dysfunction in Duchenne muscular dystrophy is restored by bradykinin through upregulation of eNOS and nNOS.

    OpenAIRE

    Dabiré, Hubert; Barthélémy, Inès; Blanchard-Gutton, Nicolas; Sambin, Lucien; Sampedrano, Carolina Carlos; Gouni, Vassiliki; Unterfinger, Yves; Aguilar, Pablo; Thibaud, Jean-Laurent; Ghaleh, Bijan; Bizé, Alain; Pouchelon, Jean-Louis; Blot, Stéphane; Berdeaux, Alain; Hittinger, Luc

    2012-01-01

    Little is known about the vascular function and expression of endothelial and neuronal nitric oxide synthases (eNOS and nNOS) in Duchenne muscular dystrophy (DMD). Bradykinin is involved in the regulation of eNOS expression induced by angiotensin-converting enzyme inhibitors. We characterized the vascular function and eNOS and nNOS expression in a canine model of DMD and evaluated the effects of chronic bradykinin treatment. Vascular function was examined in conscious golden retriever muscula...

  4. A Dual Role of erbB2 in Myelination and in Expansion of the Schwann Cell Precursor Pool

    OpenAIRE

    Garratt, A.N.; Voiculescu, O.; Topilko, P.; Charnay, P; Birchmeier, C.

    2000-01-01

    Neuregulin-1 provides an important axonally derived signal for the survival and growth of developing Schwann cells, which is transmitted by the ErbB2/ErbB3 receptor tyrosine kinases. Null mutations of the neuregulin-1, erbB2, or erbB3 mouse genes cause severe deficits in early Schwann cell development. Here, we employ Cre-loxP technology to introduce erbB2 mutations late in Schwann cell development, using a Krox20-cre allele. Cre-mediated erbB2 ablation occurs perinatally in peripheral nerves...

  5. EphB2 guides axons at the midline and is necessary for normal vestibular function

    Science.gov (United States)

    Cowan, C. A.; Yokoyama, N.; Bianchi, L. M.; Henkemeyer, M.; Fritzsch, B.

    2000-01-01

    Mice lacking the EphB2 receptor tyrosine kinase display a cell-autonomous, strain-specific circling behavior that is associated with vestibular phenotypes. In mutant embryos, the contralateral inner ear efferent growth cones exhibit inappropriate pathway selection at the midline, while in mutant adults, the endolymph-filled lumen of the semicircular canals is severely reduced. EphB2 is expressed in the endolymph-producing dark cells in the inner ear epithelium, and these cells show ultrastructural defects in the mutants. A molecular link to fluid regulation is provided by demonstrating that PDZ domain-containing proteins that bind the C termini of EphB2 and B-ephrins can also recognize the cytoplasmic tails of anion exchangers and aquaporins. This suggests EphB2 may regulate ionic homeostasis and endolymph fluid production through macromolecular associations with membrane channels that transport chloride, bicarbonate, and water.

  6. receptores

    Directory of Open Access Journals (Sweden)

    Salete Regina Daronco Benetti

    2006-01-01

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

  7. 维生素B2

    Institute of Scientific and Technical Information of China (English)

    郭红卫

    2007-01-01

    维生素B2又称核黄素(riboflavin)。最初人们于19世纪后期认识到,在天然乳清中存在着一种可溶于水的能产生黄色荧光的物质,可预防皮肤炎症。1933年由几个科研小组将其分离出来,并命名为核黄素,意指其来源于卵黄素、肝黄素和尿黄素。

  8. Identification of novel nuclear localization signal within the ErbB-2 protein

    Institute of Scientific and Technical Information of China (English)

    Qiao Qiao CHEN; Xiao Ying CHEN; Yun Yun JIANG; Jing LIU

    2005-01-01

    ErbB2,a member of the receptor tyrosine kinase family,is frequently over-expressed in breast cancer.Proteolysis of the extracellular domain of ErbB2 results in constitutive activation of ErbB2 kinase.Recent study reported that ErbB2 is found in the nucleus.Here,we showed that ErbB2 is imported into the nucleus through a nuclear localization signal (NLS)-mediated mechanism.The NLS sequence KRRQQKIRKYTMRR (aa655-668) contains three clusters of basic amino acids and it is sufficient to target GFP into the nucleus.However,mutation in any basic amino acid cluster of this NLS sequence significantly affects its nuclear localization.Furthermore,it was found that this NLS is essential for the nuclear localization of ErbB2 since the intracellular domain of Erb2 lacking NLS completely abrogates its nuclear translocation.Taken together,our study identified a novel nuclear localization signal and reveals a novel mechanism underlying ErbB2 nuclear trafficking and localization.

  9. Electronic states of BP, BP +, BP -, B 2P 2, B2P2- and B2P2+

    Science.gov (United States)

    Linguerri, Roberto; Komiha, Najia; Oswald, Rainer; Mitrushchenkov, Alexander; Rosmus, Pavel

    2008-05-01

    Using augmented sextuple zeta basis sets and internally contracted multireference configuration interaction (MRCI) wavefunctions, potential energy, electric dipole and transition moments have been computed for the X 3Π, a 1Σ +, b 1Π and A 3Σ - states of BP, X 2Σ + and A 2Π states of BP - and X 4Σ - and A 4Π states of BP +. From these data spectroscopic constants, radiative transition probabilities and photoelectron spectra of BP - and BP have been evaluated. The non-vanishing spin-orbit coupling elements between the four low lying triplet and singlet states of the neutral BP have also been calculated from MRCI wavefunctions. The treatment of the corresponding perturbations in the manifold of dense rovibrational states in the three lowest states would require a precise knowledge of the electronic excitation energies. Our best singlet-triplet separations (X-a) are calculated to be 2412 cm -1 (MRCI) and 2482 cm -1 (restricted coupled cluster with perturbative triples (RCCSD(T))) with an estimated error bound of about ±200 cm -1. All three states have long radiative lifetimes with cascading among the rovibrational levels of different states. The ionization energy IE e of BP is calculated to be 9.22 eV (MRCI) and 9.48 eV (RCCSD(T)), the electron affinity EA e 2.51 eV (MRCI) and 2.74 eV (RCCSD(T)). The photoelectron spectra of BP and BP - have been obtained from the Franck-Condon factors of the MRCI potentials. For the UV spectroscopy the dipole allowed radiative transition probabilities are given for A 3Σ - ↔ X 3Π, b 1Π ↔ a 1Σ + of BP, A 2Π ↔ X 2Σ + of BP - and A 4Π ↔ X 4Σ - of BP +. The ionization energy IE e of B 2P 2 of 8.71 eV and the electron affinity EA e of 2.34 eV have been calculated by the RCCSD(T)/aVQZ approach. Also the harmonic vibrational wavenumbers for the electronic ground states of the ions B2P2+ and B2P2- are given.

  10. Procyanidin dimer B2-mediated IRAK-M induction negatively regulates TLR4 signaling in macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Sung, Nak-Yun [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Yang, Mi-So [Department of Microbiology, Infection Signaling Network Research Center, College of Medicine, Chungnam National University, Daejeon (Korea, Republic of); Song, Du-Sub [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); School of life sciences and Biotechnology, Korea University 5-ka, Anam-Dong, Sungbuk-ku, Seoul 136-701 (Korea, Republic of); Kim, Jae-Kyung; Park, Jong-Heum; Song, Beom-Seok; Park, Sang-Hyun; Lee, Ju-Woon [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Park, Hyun-Jin [School of life sciences and Biotechnology, Korea University 5-ka, Anam-Dong, Sungbuk-ku, Seoul 136-701 (Korea, Republic of); Kim, Jae-Hun [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Byun, Eui-Baek, E-mail: ebbyun80@kaeri.re.kr [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Byun, Eui-Hong, E-mail: ehbyun80@kongju.ac.k [Department of Food Science and Technology, Kongju National University, Yesan 340-800 (Korea, Republic of)

    2013-08-16

    Highlights: •Pro B2 elevated the expression of IRAK-M, a negative regulator of TLR signaling. •LPS-induced expression of cell surface molecules was inhibited by Pro B2. •LPS-induced production of pro-inflammatory cytokines was inhibited by Pro B2. •Pro B2 inhibited LPS-induced activation of MAPKs and NF-κB through IRAK-M. •Pro B2 inactivated naïve T cells by inhibiting LPS-induced cytokines via IRAK-M. -- Abstract: Polyphenolic compounds have been found to possess a wide range of physiological activities that may contribute to their beneficial effects against inflammation-related diseases; however, the molecular mechanisms underlying this anti-inflammatory activity are not completely characterized, and many features remain to be elucidated. In this study, we investigated the molecular basis for the down-regulation of toll-like receptor 4 (TLR4) signal transduction by procyanidin dimer B2 (Pro B2) in macrophages. Pro B2 markedly elevated the expression of the interleukin (IL)-1 receptor-associated kinase (IRAK)-M protein, a negative regulator of TLR signaling. Lipopolysaccharide (LPS)-induced expression of cell surface molecules (CD80, CD86, and MHC class I/II) and production of pro-inflammatory cytokines (tumor necrosis factor-α, IL-1β, IL-6, and IL-12p70) were inhibited by Pro B2, and this action was prevented by IRAK-M silencing. In addition, Pro B2-treated macrophages inhibited LPS-induced activation of mitogen-activated protein kinases such as extracellular signal-regulated kinase 1/2, p38, and c-Jun N-terminal kinase and the translocation of nuclear factor κB and p65 through IRAK-M. We also found that Pro B2-treated macrophages inactivated naïve T cells by inhibiting LPS-induced interferon-γ and IL-2 secretion through IRAK-M. These novel findings provide new insights into the understanding of negative regulatory mechanisms of the TLR4 signaling pathway and the immune-pharmacological role of Pro B2 in the immune response against the development

  11. Role of C-erbB2 expression in gallbladder cancer

    Directory of Open Access Journals (Sweden)

    Niraj Kumari

    2012-01-01

    Full Text Available Background: Gallbladder cancer (GBC is a lethal malignancy presenting at an advanced stage. The pathogenesis is not well categorized, and surgery is the only treatment available at the early stage of the disease. There have been few reports on role of growth factor receptors in GBC. C-erbB2 is one such receptor whose over-expression is being explored in GBC as one of the factors involved in carcinogenesis and possible target for therapy. Materials and Methods: One hundred and four consecutive cases of GBC were retrospectively studied with regard to clinical features, histological type, grade and stage of tumor. Immunohistochemistry for C-erbB2 was done and expression was correlated with different clinic-pathological parameters and survival. Results: C-erbB2 overexpression was seen in 9.4% cases with complete staining and both complete and incomplete staining (2+ and 3+ was seen in 13.4% cases. Eighty percent of the C-erbB2 over-expressed cases were well differentiated and in stage II to stage IV disease. Dysplasia adjacent to carcinoma did not show any expression. No correlation was found with tumor grade, stage, gall stones, and patient survival. Xanthogranulomatous inflammation was inversely correlated with C-erbB2 over-expression. Median survival was 30 months in C-erbB2 over-expressed cases, and 12 months in C-erbB2 negative cases. Conclusion: We found complete membranous staining of C-erbB2 in 9.4% of GBC which was frequent in well differentiated and stage II to stage IV tumors. C-erbB2 tumors had longer median survival than C-erbB2 negative tumors. C-erbB2 is not involved early in the carcinogenetic process as none of the dysplasia showed expression. C-erbB2 over-expression may be considered as target for therapy in advanced stage of GBC.

  12. To be or not B2B?

    CERN Document Server

    Symons, L J

    2001-01-01

    La question du commerce électronique interentreprises par le web (Business to Business, B2B) est posée actuellement par les grands groupes industriels impliqués dans le commerce mondial. Les prévisions sont imposantes, le B2B atteindra le C.A. de 3000 milliards de dollars en 2003. Les conditions d'accès, la façon de procéder des deux organisateurs (ARIBA et COMMERCE ONE) des plus grandes places de marchés actuelles, sont décrites. La base de l'énorme pyramide est le catalogue électronique multilingue UNSPSC (United Nations Standard Products and Services Classification) et l'organisation ECCMA (Electronic Commerce Code Management Association) qui gère le développement des UNSPSC codes en 8 langues. Dans ce contexte, l'auteur (re)-déclare qu'un des efforts principaux à fournir par le CERN est la création de son propre catalogue électronique. Dans la Division ST, une aide partielle à ce vaste programme pourrait être apportée par la normalisation des codes et désignations des pièces de maint...

  13. Exercise-induced increase in interstitial bradykinin and adenosine concentrations in skeletal muscle and peritendinous tissue in humans

    DEFF Research Database (Denmark)

    Langberg, H; Bjørn, C; Boushel, Robert Christopher;

    2002-01-01

    been established. Microdialysis (molecular mass cut-off 5 kDa) was performed simultaneously in calf muscle and peritendinous Achilles tissue at rest and during 10 min periods of incremental (0.75 W, 2 W, 3.5 W and 4.75 W) dynamic plantar flexion exercise in 10 healthy individuals (mean age 27 years......Bradykinin is known to cause vasodilatation in resistance vessels and may, together with adenosine, be an important regulator of tissue blood flow during exercise. Whether tissue concentrations of bradykinin change with exercise in skeletal muscle and tendon-related connective tissue has not yet...... interstitial concentration of bradykinin rose in response to exercise both in skeletal muscle (from 23.1 +/- 4.9 nmol l(-1) to 110.5 +/- 37.9 nmol l(-1); P <0.05) and in the peritendinous tissue (from 27.7 +/- 7.8 nmol l(-1) to 105.0 +/- 37.9 nmol l(-1); P <0.05). In parallel, the adenosine concentration...

  14. Relaxation to bradykinin in bovine pulmonary supernumerary arteries can be mediated by both a nitric oxide-dependent and -independent mechanism

    Science.gov (United States)

    Tracey, A; Bunton, D; Irvine, J; MacDonald, A; Shaw, A M

    2002-01-01

    The aim of the present study was to determine the relative contribution of prostanoids, nitric oxide and K+ channels in the bradykinin-induced relaxation of bovine pulmonary supernumerary arteries. In endothelium-intact, but not denuded rings, bradykinin produced a concentration-dependent relaxation (pEC50, 9.6±0.1), which was unaffected by the cyclo-oxygenase inhibitor indomethacin. The nitric oxide scavenger hydroxocobalamin (200 μM, pEC50, 8.5±0.2) and the nitric oxide synthase inhibitor L-NAME (100 μM, pEC50, 8.9±0.1) and the combination of L-NAME and hydroxocobalamin (pEC50, 8.1±0.2) produced rightward shifts in the bradykinin concentration response curve. The guanylyl cyclase inhibitor ODQ (10 μM, pEC50, 9.6±0.4) did not affect the response to bradykinin. Elevating the extracellular [K+] to 30 mM did not affect the response to bradykinin but abolished the response when ODQ or L-NAME was present. The K+ channel blocker apamin (100 nM), combined with charybdotoxin (100 nM), produced a small reduction in the maximum response to bradykinin but they abolished the response to bradykinin when ODQ, L-NAME or hydroxocobalamin were present. Apamin (100 nM) combined with iberiotoxin (100 nM) also reduced the response to bradykinin in the presence of hydroxocobalamin or L-NAME. The concentration response curve for sodium nitroprusside-induced relaxation was abolished by ODQ (10 μM) and shifted to the right by apamin and charybdotoxin. These studies suggest that in bovine pulmonary supernumerary arteries bradykinin can stimulate the formation of nitric oxide and activate an EDHF-like mechanism and that either of these pathways alone can mediate the bradykinin-induced relaxation. In addition nitric oxide, acting through guanylyl cyclase, can activate an apamin/charbydotoxin-sensitive K+ channel in this tissue. PMID:12359636

  15. CD13/APN regulates endothelial invasion and filopodia formation

    OpenAIRE

    Petrovic, Nenad; Schacke, Wolfgang; Gahagan, J. Reed; O'Conor, Catherine A.; Winnicka, Beata; Conway, Rebecca E.; Mina-Osorio, Paola; Shapiro, Linda H.

    2007-01-01

    CD13/aminopeptidase N is a transmembrane peptidase that is induced in the vasculature of solid tumors and is a potent angiogenic regulator. Here, we demonstrate that CD13 controls endothelial cell invasion in response to the serum peptide bradykinin by facilitating signal transduction at the level of the plasma membrane. Inhibition of CD13 abrogates bradykinin B2 receptor internalization, leading to the attenuation of downstream events such as bradykinin-induced activation of Cdc42 and filopo...

  16. Taking the sting out of pain

    OpenAIRE

    Nagy, I.; Paule, C; White, J.; Urban, L.

    2007-01-01

    While the role of the brain kallikrein-kinin system in the development of various pathological processes, such as oedema formation following brain injury or induction of central hypertonia has generated major interest, the possible role of this system in nociceptive processing has received little attention. In their present paper, Mortari et al. (2007) show that bradykinin B2 receptor activation in the brain by the bradykinin analogue, Thr6-bradykinin, isolated from the venom of the social wa...

  17. Chimeric DNA Vaccines against ErbB2+ Carcinomas: From Mice to Humans

    International Nuclear Information System (INIS)

    DNA vaccination exploits a relatively simple and flexible technique to generate an immune response against microbial and tumor-associated antigens (TAAs). Its effectiveness is enhanced by the application of an electrical shock in the area of plasmid injection (electroporation). In our studies we exploited a sophisticated electroporation device approved for clinical use (Cliniporator, IGEA, Carpi, Italy). As the target antigen is an additional factor that dramatically modulates the efficacy of a vaccine, we selected ErbB2 receptor as a target since it is an ideal oncoantigen. It is overexpressed on the cell membrane by several carcinomas for which it plays an essential role in driving their progression. Most oncoantigens are self-tolerated molecules. To circumvent immune tolerance we generated two plasmids (RHuT and HuRT) coding for chimeric rat/human ErbB2 proteins. Their immunogenicity was compared in wild type mice naturally tolerant for mouse ErbB2, and in transgenic mice that are also tolerant for rat or human ErbB2. In several of these mice, RHuT and HuRT elicited a stronger anti-tumor response than plasmids coding for fully human or fully rat ErbB2. The ability of heterologous moiety to blunt immune tolerance could be exploited to elicit a significant immune response in patients. A clinical trial to delay the recurrence of ErbB2+ carcinomas of the oral cavity, oropharynx and hypopharynx is awaiting the approval of the Italian authorities

  18. Chimeric DNA Vaccines against ErbB2{sup +} Carcinomas: From Mice to Humans

    Energy Technology Data Exchange (ETDEWEB)

    Quaglino, Elena; Riccardo, Federica; Macagno, Marco; Bandini, Silvio; Cojoca, Rodica; Ercole, Elisabetta [Molecular Biotechnology Center, Department of Clinical and Biological Sciences, University of Turin, 10126 Turin (Italy); Amici, Augusto [Department of Molecular Cellular and Animal Biology, University of Camerino, 62032 Camerino (Italy); Cavallo, Federica, E-mail: federica.cavallo@unito.it [2 Department of Molecular Cellular and Animal Biology, University of Camerino, 62032 Camerino (Italy)

    2011-08-10

    DNA vaccination exploits a relatively simple and flexible technique to generate an immune response against microbial and tumor-associated antigens (TAAs). Its effectiveness is enhanced by the application of an electrical shock in the area of plasmid injection (electroporation). In our studies we exploited a sophisticated electroporation device approved for clinical use (Cliniporator, IGEA, Carpi, Italy). As the target antigen is an additional factor that dramatically modulates the efficacy of a vaccine, we selected ErbB2 receptor as a target since it is an ideal oncoantigen. It is overexpressed on the cell membrane by several carcinomas for which it plays an essential role in driving their progression. Most oncoantigens are self-tolerated molecules. To circumvent immune tolerance we generated two plasmids (RHuT and HuRT) coding for chimeric rat/human ErbB2 proteins. Their immunogenicity was compared in wild type mice naturally tolerant for mouse ErbB2, and in transgenic mice that are also tolerant for rat or human ErbB2. In several of these mice, RHuT and HuRT elicited a stronger anti-tumor response than plasmids coding for fully human or fully rat ErbB2. The ability of heterologous moiety to blunt immune tolerance could be exploited to elicit a significant immune response in patients. A clinical trial to delay the recurrence of ErbB2{sup +} carcinomas of the oral cavity, oropharynx and hypopharynx is awaiting the approval of the Italian authorities.

  19. Impaired cortical neurogenesis in plexin-B1 and -B2 double deletion mutant.

    Science.gov (United States)

    Daviaud, Nicolas; Chen, Karen; Huang, Yong; Friedel, Roland H; Zou, Hongyan

    2016-08-01

    Mammalian cortical expansion is tightly controlled by fine-tuning of proliferation and differentiation of neural progenitors in a region-specific manner. How extrinsic cues interface with cell-intrinsic programs to balance proliferative versus neurogenic decisions remains an unsolved question. We examined the function of Semaphorin receptors Plexin-B1 and -B2 in corticogenesis by generating double mutants, whereby Plexin-B2 was conditionally ablated in the developing brain in a Plexin-B1 null mutant background. Absence of both Plexin-Bs resulted in cortical thinning, particularly in the caudomedial cortex. Plexin-B1/B2 double, but not single, mutants exhibited a reduced neural progenitor pool, attributable to decreased proliferation and an altered division mode favoring cell cycle exit. This resulted in deficient production of neurons throughout the neurogenic period, proportionally affecting all cortical laminae. Consistent with the in vivo data, cultured neural progenitors lacking both Plexin-B1 and -B2 displayed decreased proliferative capacity and increased spontaneous differentiation. Our study therefore defines a novel function of Plexin-B1 and -B2 in transmitting extrinsic signals to maintain proliferative and undifferentiated states of neural progenitors. As single mutants displayed no apparent cortical defects, we conclude that Plexin-B1 and -B2 play redundant or compensatory roles during forebrain development to ensure proper neuronal production and neocortical expansion. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 882-899, 2016. PMID:26579598

  20. Bradykinin enhances membrane electrical activity of pancreatic beta cells in the presence of low glucose concentrations

    Directory of Open Access Journals (Sweden)

    A.S. Moura

    2000-09-01

    Full Text Available In most of cells bradykinin (BK induces intracellular calcium mobilization. In pancreatic beta cells intracellular calcium is a major signal for insulin secretion. In these cells, glucose metabolism yields intracellular ATP which blocks membrane potassium channels. The membrane depolarizes, voltage-dependent Ca2+ channels are activated and the intracellular calcium load allows insulin secretion. Repolarization occurs due to activation of the Ca2+-dependent K+ channel. The insulin secretion depends on the integrity of this oscillatory process (bursts. Therefore, we decided to determine whether BK (100 nM induces bursts in the presence of a non-stimulatory glucose concentration (5.6 mM. During continuous membrane voltage recording, our results showed that bursts were obtained with 11 mM glucose, blocked with 5.6 mM glucose and recovered with 5.6 mM glucose plus 100 nM BK. Thus, the stimulatory process obtained in the presence of BK and of a non-stimulatory concentration of glucose in the present study suggests that BK may facilitate the action of glucose on beta cell secretion.

  1. Duration and distribution of experimental muscular hyperalgesia in humans following combined infusions of serotonin and bradykinin

    DEFF Research Database (Denmark)

    Babenko, Victor; Svensson, Peter; Graven-Nielsen, Thomas;

    2000-01-01

    The present study examined distribution and duration of muscle hyperalgesia to pressure stimuli after intramuscular bolus-infusions of serotonin (5-HT, 20 nmol) and bradykinin (BKN, 10 nmol) in 10 volunteers. Infusions were given into the tibialis anterior (TA) muscle over 20 s with an inter-infusions...... interval of 3 min. Infusions of isotonic saline (NaCl, 0.9%) were given as control. Pain intensity was continuously scored on a visual analogue scale (VAS), and subjects drew the distribution of the pain areas on an anatomical map. Pressure pain thresholds (PPTs) were assessed with an electronic algometer......, 40, and 60 min after infusions. The VAS-peak after BKN was significantly higher (P<0.05) compared with 5-HT and the second infusion of NaCl. The duration of the increase in VAS after 5-HT+BKN was significantly longer (P<0.05) compared with the infusions of NaCl. The local pain area after infusion of...

  2. Some Considerations on B2B in China%对我国B2B的一些思考

    Institute of Scientific and Technical Information of China (English)

    王进; 和金生

    2001-01-01

    B2B的现状入手,指出中国非常需要B2B;从B2B企业的内部环境对B2B出现的问题加以分析,并提出了相关对策,最后对B2B给予了展望。%Based on the analysis of the present situation of B2B,it indicates the requirement of B2B in China. Then,it analyses the questions in the implementation of B2B in enterprises and puts forward some countermeasures. Finally,the prospect of B2B development is given.

  3. Selective inhibition by antiflamrnin-2 of thromboxane B2 release from isolated and perfused guinea-pig lung

    Directory of Open Access Journals (Sweden)

    Lidia Sautebin

    1992-01-01

    Full Text Available Antiflammin-2 (AF2 is a nonapeptide corresponding to the amino acid residues 246–254 of lipocortin-1 showing anti-inflammatory activity both in vitro and in vivo. The effect of AF2 on the thromboxane B2 (TXB2 and histamine release from isolated and perfused guinea-pig lungs has been studied. AF-2 (10–100 nM inhibited leukotriene C4- (LTC4 (3 ng and antigen-induced (ovalbumin, 1 mg TXB2 release in normal and sensitized lungs, respectively. In contrast AF-2 (100 nM did not modify TXB2 release induced by histamine (5 μg or bradykinin (5 μg in normal lungs. Antigen-induced histamine release was not affected by 100 nM AF-2 infusion. When tested in chopped lung fragments AF-2 (0.1–25 μM did not modify the release of histamine and TXB2 induced by antigen (ovalbumin, 10 μg ml−1 or calcium ionophore A 23187 (1 μM. Our results show that the inhibitory effect of AF-2 on TXB2 release is selective and depends on the stimulus applied. In this respect AF-2 mimics, at least in part, the actions of both glucocorticoids and lipocortin-1.

  4. TRUST IN B2B E-MARKETPLACES

    Directory of Open Access Journals (Sweden)

    SEBASTIAN KOT

    2011-01-01

    Full Text Available The paper presents background of B2B exchanges and review of their forms and functionalities. The benefits and fails reasons are noticed. European enterprises interest in B2B trade is next aspect of consideration. Finally, the trust barriers of B2B exchanges are presented.

  5. Component Based System Framework for Dynamic B2B Interaction

    NARCIS (Netherlands)

    Hu jinmin, H.J.; Grefen, P.W.P.J.

    2002-01-01

    Business-to-business (B2B) collaboration is becoming a pivotal way to bring today's enterprises to success in the dynamically changing, e-business environment. Though many business-to-business protocols are developed to support B2B interaction, none are generally accepted. A B2B system should suppor

  6. 26 CFR 1.663(b)-2 - Election.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Election. 1.663(b)-2 Section 1.663(b)-2 Internal... TAXES Estates and Trusts Which May Accumulate Income Or Which Distribute Corpus § 1.663(b)-2 Election. (a) Manner and time of election; irrevocability—(1) When return is required to be filed. If a...

  7. Functional expression of a single-chain antibody to ErbB-2 in plants and cell-free systems

    OpenAIRE

    Benevolo Maria; Natali Pier; Martayan Aline; Fraioli Rocco; Tornambé Andrea; Sperandei Maria; Di Donato Monica; Novelli Flavia; Pietraforte Immacolata; Lombardi Alessio; Galeffi Patrizia; Mottolese Marcella; Ylera Francisco; Cantale Cristina; Giacomini Patrizio

    2006-01-01

    Abstract Background Aberrant signaling by ErbB-2 (HER 2, Neu), a member of the human Epidermal Growth Factor (EGF) receptor family, is associated with an aggressive clinical behaviour of carcinomas, particularly breast tumors. Antibodies targeting the ErbB-2 pathway are a preferred therapeutic option for patients with advanced breast cancer, but a worldwide deficit in the manufacturing capacities of mammalian cell bioreactors is foreseen. Methods Herein, we describe a multi-platform approach ...

  8. Electronic Commerce in Tourism in China: B2B or B2C?

    Science.gov (United States)

    Li, Hongxiu; Suomi, Reima

    E-commerce has significantly changed the distribution channels of travel products in the world including China. Online channels are growing important in travel service distribution. In China tourism industry has been developed rapidly with the economic development, more and more international travel service providers are trying to expand their Chinese market through the Internet. This paper sheds lights on the e-commerce development models in China for international travel service providers. It explores the current e-tourism in China from the three different participants in the value chain in tourism industry - consumer, travel agent and travel service provider. The paper also identifies the barriers in B2C arena in international outbound travel market, and discusses the possible approaches for international travel service providers to develop their e-commerce in the huge Chinese market. The results in this study reveal that international travel service providers should focus on B2B model to expand their electronic market in China. B2C development in tourism largely depends on the change of Chinese customers' behavior and the change of international tourism regulations. The findings of the study are expected to assist international travel service providers to understand current e-tourism in China and to support their planning for future e-commerce development in China.

  9. Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition

    Directory of Open Access Journals (Sweden)

    Flores Juana M

    2010-07-01

    Full Text Available Abstract Background ErbB2-positive breast cancer is characterized by highly aggressive phenotypes and reduced responsiveness to standard therapies. Although specific ErbB2-targeted therapies have been designed, only a small percentage of patients respond to these treatments and most of them eventually relapse. The existence of this population of particularly aggressive and non-responding or relapsing patients urges the search for novel therapies. The purpose of this study was to determine whether cannabinoids might constitute a new therapeutic tool for the treatment of ErbB2-positive breast tumors. We analyzed their antitumor potential in a well established and clinically relevant model of ErbB2-driven metastatic breast cancer: the MMTV-neu mouse. We also analyzed the expression of cannabinoid targets in a series of 87 human breast tumors. Results Our results show that both Δ9-tetrahydrocannabinol, the most abundant and potent cannabinoid in marijuana, and JWH-133, a non-psychotropic CB2 receptor-selective agonist, reduce tumor growth, tumor number, and the amount/severity of lung metastases in MMTV-neu mice. Histological analyses of the tumors revealed that cannabinoids inhibit cancer cell proliferation, induce cancer cell apoptosis, and impair tumor angiogenesis. Cannabinoid antitumoral action relies, at least partially, on the inhibition of the pro-tumorigenic Akt pathway. We also found that 91% of ErbB2-positive tumors express the non-psychotropic cannabinoid receptor CB2. Conclusions Taken together, these results provide a strong preclinical evidence for the use of cannabinoid-based therapies for the management of ErbB2-positive breast cancer.

  10. B2(BO)6 0/- and B 2(BS) 6 0/- doubly bridged structures containing BO or BS as ligands.

    Science.gov (United States)

    Li, Da-Zhi; Li, Si-Dian

    2014-09-01

    The investigation on the geometrical and electronic properties of B(2)(BO)(6) (0/-) and B(2)(BS)(6) (0/-) has been performed by density functional theory (DFT) using the B3LYP and BP86 methods. The chemical bonding in B(2)A(6) (A = H, BO, and BS) series is elucidated through the recently developed adaptive natural density partitioning (AdNDP). D(2h) B(2)(BO)(6) and B(2)(BS)(6) were found to possess two bridging η (2)-BO or η (2)-BS groups, as well as four terminal BO or BS groups that are analogs of diborane B(2)H(6). D(2)h B(2)(BO)(6) (-) and B(2)(BS)(6) (-) with two bridging η (2)-BO or η (2)-BS groups which are more stable than their corresponding D(3d) structures. The binding energy of B(2)(BO)(6) and B(2)(BS)(6) with respect to B(2)(BO)(6) (D2h) → 2B(BO)(3) (D(3h)) and B(2)(BS)(6)(D(2h)) → 2B(BS)(3) (D(3h)) are estimated to be (△)E = 19.8 and 40.6 kcal mol(-1) at CCSD(T)//B3LYP level, respectively. This finding advances the boronyl chemistry and helps establish the isolobal analogy between boron-rich oxide clusters and boranes. PMID:25159274

  11. Excitation of afferent fibres in the cardiac sympathetic nerves induced by coronary occlusion and injection of bradykinin. The influence of acetylsalicylic acid and dipyron.

    Science.gov (United States)

    Vogt, A; Vetterlein, F; dal Ri, H; Schmidt, G

    1979-05-01

    Afferent impulse activity was recorded in single fibres of the inferior cardiac sympathetic nerve of the cat. When the descending branch of the left coronary artery was ligated for 60 sec an enhancement of afferent impulses was recorded. Elevations in discharge frequency were also induced by injecting bradykinin, epinephrine, and isoprenaline or by general hypoxia due to interruption of the artificial ventilation. When these procedures were after pretreatment with the analgesic agents, acetylsalicylic acid or dipyron a reduction in spike discharge was observed only with bradykinin after application of acetylsalicylic acid. No influence of these pretreatments on the effects of coronary occlusion, general hypoxia and injection of epinephrine and isoprenaline could be observed. These results suggest that bradykinin does not predominate as mediator substance in eliciting ischemic heart pain. PMID:485722

  12. Positron lifetime spectroscopy of vitreous B2O3

    International Nuclear Information System (INIS)

    A comparison is made of the structural data obtained by positron lifetime spectroscopy (PLS) for vitreous B2O3 (v-B2O3) and crystalline B2O3 (c-B2O3). Samples of v-B2O3 were dried by holding the melt at 1350K to reduce residual OH groups. Fast quenching and slow cooling were used to obtain glasses having different fictive structures. According to the literature, B3O6 rings are thought to be formed during slow cooling of v-B2O3. PLS measurements show that both the intensity value and the long lifetime component (t3) associated with positron decay in cavities and lifetime component (t1) associated with the positron annihilation in the bulk are different for v-B2O3 and c-B2O3. The low intensity of t3 for c-B2O3 and its high value for v-B2O3 is argued to be due to the presence of different structural units in the two states of B2O3

  13. A comparison of the effects of captopril and enalapril on skin responses to intradermal bradykinin and skin blood flow in the human forearm.

    OpenAIRE

    LI KAM WA, T. C.; Cooke, E D; Turner, P

    1993-01-01

    1. The effects of captopril and enalapril on skin responses to intradermal injections of bradykinin and skin blood flow in the forearm were investigated in this randomised, double-blind, placebo-controlled, cross-over study. 2. Intradermal injections of 0, 1, 2.5 and 5 micrograms of bradykinin in 0.9% sodium chloride were made into the forearm of twelve healthy volunteers before and at 2, 6 and 24 h after single oral doses of 25 mg captopril, 10 mg enalapril or placebo. Forearm skin blood flo...

  14. Bradykinin-induced release of PGI2 from aortic endothelial cell lines: responses mediated selectively by Ca2+ ions or a staurosporine-sensitive kinase.

    OpenAIRE

    Parsaee, H.; McEwan, J R; MacDermot, J

    1993-01-01

    1. Bradykinin (100 nM) triggers release of nitric oxide and prostacyclin from both AG07680A and AG04762 bovine cultured aortic endothelial cells. The exposure of these cells to bradykinin is in each case associated with a striking rise in intracellular calcium ion concentration. 2. Exposure of AG07680A cells to 250 nM ionomycin was followed also by a significant release of prostacyclin, whereas 250 nM ionomycin had no capacity to stimulate release of prostacyclin from AG04762 cells. 3. There ...

  15. The effects of formoterol on plasma exudation produced by a localized acute inflammatory response to bradykinin in the tracheal mucosa of rats in vivo.

    OpenAIRE

    O'Donnell, S. R.; Anderson, G. P.

    1995-01-01

    1. The effects of formoterol, a beta 2-adrenoceptor agonist, on plasma protein exudation and microvascular permeability induced by topical, i.e. applied onto the tracheal mucosal surface, bradykinin (10 nmol; 20 microM, 5 min, 0.1 ml min-1) were studied in a perfused segment of trachea prepared in situ in anaesthetized rats. 2. Bradykinin increased the amount of plasma (fluorimetric assay for protein) in the perfusate (response; 10.98 +/- 0.357 microliters, n = 69; total increase in plasma ov...

  16. A research on B2B modes%B2B电子商务模式研究

    Institute of Scientific and Technical Information of China (English)

    黎梅

    2001-01-01

    21世纪是电子商务时代,在对最具潜力的B2B电子商务模式的网站调查基础上,对B2B电子商务的模式进行了详细分类和分析,为我国的B2B电子商务经营者制订切实可行的发展策略和营销策略提供了参考和借鉴.从目前情况和长远趋势来看,在B2B电子商务的4种模式中,其中企业B2B网站、B2B交易场、垂直型的B2B网站在中国将有很好的发展趋势.

  17. Importance of the terminal α-amino group of bradykinin and some kynins on capillary permeability increase

    International Nuclear Information System (INIS)

    A simple and reliable method is described for the quantitative evaluation of vascular permeability increase induced by vasoactive drugs with Evans blue labelled with iodine-125 or 131. By using this method the importance of α-amino group of bradykinin (Bk), kallidin (Kd) and methionyl-kallidin (Met-Kd) on the biological activity were studied after reacting the kinins with pyridoxal 5'-phosphate followed by reduction with sodium borohydride. Phosphopyridoxyl-kinins were formed leaving free the guanidino groups. Aminoacid analysis of phosphopyridoxyl-kinin showed that the efficiency of the reaction was extremely good in the blockage of α-amino groups [phosphopyridoxyl-bradikinin (PP-Bk) = 98,8%, phosphopyridoxyl-kallidin (PP-Kd) = 95,2%, phosphopyridoxyl-methionyl-kallidin (PP-Met-Kd) = 98,0%. Log dose-response curves were obtained for Bk, Kd, Met-Kd, acetyl-bradykinin (Ac-Bk), PP-Bk, PP-Kd and PP-Met-Kd and the relative potencies calculated through the Lineweaver-Burk plots. The relative potencies were: PP-Bk about 16% the activity of Bk, Ac-Bk about 31% the activity of Bk, PP-Kd about 17% the activity of Kd, PP-Met-Kd about 12% the activity of Met-Kd. The results show that the terminal α-amino group of kinins is important in the mechanisms of biological activity. (Author)

  18. Enhancement of arachidonic acid signaling pathway by nicotinic acid receptor HM74A

    International Nuclear Information System (INIS)

    HM74A is a G protein-coupled receptor for nicotinic acid (niacin), which has been used clinically to treat dyslipidemia for decades. The molecular mechanisms whereby niacin exerts its pleiotropic effects on lipid metabolism remain largely unknown. In addition, the most common side effect in niacin therapy is skin flushing that is caused by prostaglandin release, suggesting that the phospholipase A2 (PLA2)/arachidonic acid (AA) pathway is involved. Various eicosanoids have been shown to activate peroxisome-proliferator activated receptors (PPAR) that play a diverse array of roles in lipid metabolism. To further elucidate the potential roles of HM74A in mediating the therapeutic effects and/or side effects of niacin, we sought to explore the signaling events upon HM74A activation. Here we demonstrated that HM74A synergistically enhanced UTP- and bradykinin-mediated AA release in a pertussis toxin-sensitive manner in A431 cells. Activation of HM74A also led to Ca2+-mobilization and enhanced bradykinin-promoted Ca2+-mobilization through Gi protein. While HM74A increased ERK1/2 activation by the bradykinin receptor, it had no effects on UTP-promoted ERK1/2 activation.Furthermore, UTP- and bradykinin-mediated AA release was significantly decreased in the presence of both MAPK kinase inhibitor PD 098059 and PKC inhibitor GF 109203X. However, the synergistic effects of HM74A were not dramatically affected by co-treatment with both inhibitors, indicating the cross-talk occurred at the receptor level. Finally, stimulation of A431 cells transiently transfected with PPRE-luciferase with AA significantly induced luciferase activity, mimicking the effects of PPARγ agonist rosiglitazone, suggesting that alteration of AA signaling pathway can regulate gene expression via endogenous PPARs

  19. Endothelial 5-HT receptors mediate relaxation of porcine pulmonary arteries in response to ergotamine and dihydroergotamine.

    OpenAIRE

    Glusa, E; Roos, A. (Anna)

    1996-01-01

    1. The aim of the present study was to investigate whether antimigraine ergot compounds may act at endothelial 5-hydroxytryptamine (5-HT) receptors which trigger the release of endothelium-derived relaxing factor (EDRF). Changes in tone of porcine isolated pulmonary arteries were measured isometrically. The integrity of the endothelium was assessed by the bradykinin-induced relaxation of prostaglandin F2 alpha (PGF2 alpha, 3 microM)-precontracted vessels. 2. The ergot derivatives ergotamine, ...

  20. Organizational patterns for knowledge capture in B2B engagements

    OpenAIRE

    Niwe, Moses

    2010-01-01

    The purpose of this research is to present a means of knowledge capture in form of patterns that are solutions to reoccurring problems for business-to-business (B2B) organizations. Using empirical data, we examine the processes involved in the B2B engagement and capture valuable solutions as best practices. The collection of patterns forms a pattern language for B2B engagements that addresses operational, communication and collaboration areas of the B2B environment. The thesis is organized in...

  1. Compton profile study of ZrB2

    Science.gov (United States)

    Vyas, V.; Kumar, R.; Sharma, G.; Sharma, B. K.

    2013-06-01

    In this paper, we investigate the Compton profile of ZrB2. The theoretical Compton profile of ZrB2 is computed within the framework of density functional theory (DFT) based on linear combination of atomic orbitals (LCAO). To compare the spherically averaged theoretical values, the measurement on polycrystalline ZrB2 is performed using 59.54 keV gamma-rays emanating from an 241Am radioisotope. To estimate the charge transfer in ZrB2, ionic model based calculations have also been performed which suggest transfer of electron from Zr to B atoms.

  2. Lack of evidence for AT1R/B2R heterodimerization in COS-7, HEK293, and NIH3T3 cells: how common is the AT1R/B2R heterodimer?

    DEFF Research Database (Denmark)

    Hansen, Jakob L; Hansen, Jonas T; Speerschneider, Tobias;

    2008-01-01

    dimerization using bioluminescence resonance energy transfer and regulated secretion/aggregation technology. However, although both the AT1Rs and B2Rs were functional in our systems and the systems were fine tuned to detect small changes in receptor function, we failed to detect any functional modulation...

  3. NMR relaxation rates and Knight shifts in MgB2 and AlB2: theory versus experiments

    International Nuclear Information System (INIS)

    We have performed 11B NMR measurements in 11B enriched MgB2 powder sample in the normal phase. The Knight shift was accurately determined by using the magic angle spinning technique. Results for 11B and 27Al Knight shifts (K) and relaxation rates (1/T1) are also reported for AlB2. The data show a dramatic decrease of both K and 1/T1 for 11B in AlB2 with respect to MgB2. We compare experimental results with ab initio calculated NMR relaxation rates and Knight shifts. The experimental values for 1/T1 and K are in most cases in good agreement with the theoretical results. We show that the decrease of K and 1/T1 for 11B is consistent with a drastic drop of the density of states at the boron site in AlB2 with respect to MgB2

  4. Correlation of c-erbB-2, EGF and EGFR expression with postoperative survival of patients with advanced carcinoma of the stomach.

    OpenAIRE

    Katarzyna Guzinska-Ustymowicz; Jolanta Czyzewska; Andrzej Kemona

    2010-01-01

    The c-erbB-2 (HER-2/neu), EGF and EGFR (erbB-1) proteins, members of the epidermal growth factor receptor family, play a role in cell growth by binding to cell membrane receptors. The aim of the current study was to evaluate the expression of c-erbB-2, EGF and EGFR in advanced gastric carcinoma and to analyze its relationship with chosen anatomo-clinical parameters and prognosis. Standard avidin-biotin-peroxidase was used for c-erbB-2, EGF and EGFR immuno-histochemical staining (Novostain Sup...

  5. Removal of oxide contamination from TiB2 powders

    International Nuclear Information System (INIS)

    Commerical TiB2 powders from the carbothermic process are invariably contaminated with oxygen. Contamination is usually caused by surface oxidation during grinding or comminution. Surface oxide contamination, which commonly occurs in fine TiB2 powders and affects their properties, can be removed by treatment with BCl3(g) at 6500C

  6. Hexagonal OsB2: Sintering, microstructure and mechanical properties

    International Nuclear Information System (INIS)

    Highlights: • ReB2-type hexagonal OsB2 powder has been densified by spark plasma sintering. • The sintered OsB2 contains ∼80 wt.% hexagonal and ∼20 wt.% orthorhombic phases. • The average grain size of the sintered OsB2 sample was 0.56 ± 0.26 μm. • H = 31 ± 9 GPa and E = 574 ± 112 GPa measured by nanoindentation. - Abstract: The metastable high pressure ReB2-type hexagonal OsB2 bulk ceramics was produced by spark plasma sintering. The phase composition, microstructure, and mechanical behavior of the sintered OsB2 were studied by X-ray diffraction, optical microscopy, TEM, SEM, EDS, and nanoindentation. The produced ceramics was rather porous and contained a mixture of hexagonal (∼80 wt.%) and orthorhombic (∼20 wt.%) phases as identified by X-ray diffraction and EBSD analysis. Two boron-rich phases, which do not contain Os, were also identified by TEM and SEM/EDS analysis. Nanoindentation measurements yielded a hardness of 31 ± 9 GPa and Young’s modulus of 574 ± 112 GPa, indicating that the material is rather hard and very stiff; however, it is very prone to crack formation and propagation, which is indicative of a very brittle nature of this material. Improvements in the sintering regime are required in order to produce dense, homogeneous and single phase hexagonal OsB2 bulk ceramics

  7. ORM-based semantics of B2B transactions.

    NARCIS (Netherlands)

    Balsters, H.; van Blommestein, F.; Meersman, R; Herrero, P; Dillon, T

    2009-01-01

    After widespread implementation of Enterprise Resource Planning and Personal Information Management, the next wave in the application of ICT is headed towards business to business (B2B) communication. B2B has a number of specific aspects, one of them being negotiation. This aspect has been largely n

  8. EXTREMAL VECTORS FOR VERMA TYPE REPRESENTATION OF B2

    Directory of Open Access Journals (Sweden)

    Čestmír Burdík

    2013-10-01

    Full Text Available Starting from the Verma modules of the algebra B2 we explicitly construct factor representations of the algebra B2 which are connected with the unitary representation of the group SO(3, 2. We find a full set of extremal vectors for representations of this kind. So we can explicitly resolve the problem of the irreducibility of these representations.

  9. Chemical synthesis of superconducting MgB2 nanopowder

    International Nuclear Information System (INIS)

    Highlights: • MgB2 nanopowder has been synthesized by chemical method. • Powder characterized by XRD and SEM. • Superconducting behavior confirmed by susceptibility and magnetization measurements. • Nanopowder will facilitate the fabrication of small diameter MgB2 filaments. - Abstract: Superconducting MgB2 nanopowder has been synthesized through chemical reaction between lithium borohydride and magnesium hydride at relatively low temperatures. From quantitative Rietveld analysis, the average crystallite size of MgB2 powder was evaluated to be 33 nm. The superconducting transition temperature of the MgB2 nanopowder was found to be 38.8-38.9 K from magnetization and DC susceptibility measurements. Powder morphology has been evaluated by scanning electron microscopy

  10. Peptide IC-20, encoded by skin kininogen-1 of the European yellow-bellied toad, Bombina variegata, antagonizes bradykinin-induced arterial smooth muscle relaxation

    Directory of Open Access Journals (Sweden)

    Mu Yang

    2011-01-01

    Full Text Available Objectives: The objectives were to determine if the skin secretion of the European yellow-bellied toad (Bombina variegata, in common with other related species, contains a bradykinin inhibitor peptide and to isolate and structurally characterize this peptide. Materials and Methods: Lyophilized skin secretion obtained from this toad was subjected to reverse phase HPLC fractionation with subsequent bioassay of fractions for antagonism of the bradykinin activity using an isolated rat tail artery smooth muscle preparation. Subsequently, the primary structure of the peptide was established by a combination of microsequencing, mass spectroscopy, and molecular cloning, following which a synthetic replicate was chemically synthesised for bioassay. Results: A single peptide of molecular mass 2300.92 Da was resolved in HPLC fractions of skin secretion and its primary structure determined as IYNAIWP-KH-NK-KPGLL-. Database interrogation with this sequence indicated that this peptide was encoded by skin kininogen-1 previously cloned from B. variegata. The blank cycles were occupied by cysteinyl (C residues and the peptide was located toward the C-terminus of the skin kininogen, and flanked N-terminally by a classical -KR- propeptide convertase processing site. The peptide was named IC-20 in accordance (I = N-terminal isoleucine, C = C-terminal cysteine, 20 = number of residues. Like the natural peptide, its synthetic replicate displayed an antagonism of bradykinin-induced arterial smooth muscle relaxation. Conclusion: IC-20 represents a novel bradykinin antagonizing peptide from amphibian skin secretions and is the third such peptide found to be co-encoded with bradykinins within skin kininogens.

  11. Structural investigation of the ternary RM3B2 compounds

    International Nuclear Information System (INIS)

    The crystal structure of the ternary borides CeRh3B2, CeCo3B2 structure type, P6/mmm space group, a=5.470(2) A, c=3.080(2) A, Z=1, V=79.81(2) A3, ρ=9.789 g cm-3, μ=28.92 mm-1 and YIr3B2, ErIr3B2 structure type, C2/m space group, a=5.432(2) A, b=9.398(4) A, c=3.099(1) A, β=90.38(1) deg., Z=2, V=158.2(1) A3, ρ=14.425 g cm-3, μ=143.632 mm-1 were refined to R=0.0224, wR2=0.0573 and R=0.0467, wR2=0.1138, respectively, from single crystal X-ray diffraction data of the 'as cast' samples. The CeCo3B2 structure type was confirmed for the CeRh3B2 compound, a=5.47509(16) A, c=3.08143(9) A from Rietveld refinement of X-ray powder diffraction data of the sample annealed at 1070 K (RP=2.76%, RWP=4.32%, RB=4.91%, RF=4.94%). The crystal structures of the annealed at 1070 K RIr3B2 (R=Ce, Nd and Y) and YRh3B2 compounds are more complicated. Different splittings of the reflexions in the X-ray powder patterns of these compounds can be an indication of different structure models related with the CeCo3B2 and ErIr3B2 structure types

  12. Nicotine impairs cyclooxygenase-2-dependent kinin-receptor-mediated murine airway relaxations

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Yuan, E-mail: yuan.xu@ki.se; Cardell, Lars-Olaf

    2014-02-15

    Introduction: Cigarette smoke induces local inflammation and airway hyperreactivity. In asthmatics, it worsens the symptoms and increases the risk for exacerbation. The present study investigates the effects of nicotine on airway relaxations in isolated murine tracheal segments. Methods: Segments were cultured for 24 h in the presence of vehicle, nicotine (10 μM) and/or dexamethasone (1 μM). Airway relaxations were assessed in myographs after pre-contraction with carbachol (1 μM). Kinin receptors, cyclooxygenase (COX) and inflammatory mediator expressions were assessed by real-time PCR and confocal-microscopy-based immunohistochemistry. Results: The organ culture procedure markedly increased bradykinin- (selective B{sub 2} receptor agonist) and des-Arg{sup 9}-bradykinin- (selective B{sub 1} receptor agonist) induced relaxations, and slightly increased relaxation induced by isoprenaline, but not that induced by PGE{sub 2}. The kinin receptor mediated relaxations were epithelium-, COX-2- and EP2-receptor-dependent and accompanied by drastically enhanced mRNA levels of kinin receptors, as well as inflammatory mediators MCP-1 and iNOS. Increase in COX-2 and mPGES-1 was verified both at mRNA and protein levels. Nicotine selectively suppressed the organ-culture-enhanced relaxations induced by des-Arg{sup 9}-bradykinin and bradykinin, at the same time reducing mPGES-1 mRNA and protein expressions. α7-nicotinic acetylcholine receptor inhibitors α-bungarotoxin and MG624 both blocked the nicotine effects on kinin B{sub 2} receptors, but not those on B{sub 1}. Dexamethasone completely abolished kinin-induced relaxations. Conclusion: It is tempting to conclude that a local inflammatory process per se could have a bronchoprotective component by increasing COX-2 mediated airway relaxations and that nicotine could impede this safety mechanism. Dexamethasone further reduced airway inflammation together with relaxations. This might contribute to the steroid resistance seen in

  13. Synthesis and bioactivity of MSH4 oligomers prepared by an A2 + B2 strategy

    Science.gov (United States)

    Dehigaspitiya, Dilani Chathurika; Navath, Suryakiran; Weber, Craig S.; Lynch, Ronald M.; Mash, Eugene A.

    2014-01-01

    Oligomers incorporating the tetrapeptide MSH4, the minimum active sequence of melanocyte stimulating hormone, were synthesized by an A2 + B2 strategy involving microwave-assisted copper-catalyzed azide-alkyne cycloaddition. A2 contained an MSH4 core while B2 contained a (Pro-Gly)3 spacer. Soluble mixtures containing compounds with up to eight MSH4 units were obtained from oligomerizations at high monomer concentrations. The avidities of several oligomeric mixtures were evaluated by means of a competitive binding assay using HEK293 cells engineered to overexpress the melanocortin 4 receptor. When based on total MSH4 concentrations, avidities were only minimally enhanced compared with a monovalent control. The lack of variation in the effect of ligands on probe binding is consistent with high off rates for MSH4 in both monovalent and oligomeric constructs relative to that of the competing probe. PMID:26120211

  14. A complex relationship between TRAF3 and non-canonical NF-κB2 activation in B lymphocytes

    Directory of Open Access Journals (Sweden)

    Wai Wai Lin

    2013-12-01

    Full Text Available The adaptor protein TRAF3 restrains BAFF receptor (BAFFR and CD40-mediated activation of the NF-κB2 pathway in B cells. Mice lacking TRAF3 specifically in B cells revealed the critical role of TRAF3 in restraining homeostatic B cell survival. Furthermore, loss- of-function mutations of the traf3 gene have been associated with human B cell malignancies, especially multiple myeloma (MM. It has been proposed that receptor-induced TRAF3 degradation leads to stabilization of the NF-B inducing kinase NIK, and subsequent NF-κB2 activation. However, it is unclear how receptor-mediated TRAF3 degradation or loss of function contributes to B cell-specific NF-κB2 activation. In the current study, we employed two complementary models to address this question. One utilized a mutant traf3 gene found in a human MM-derived cell line called LP1. The LP1 mutant TRAF3 protein lacks the TRAF-N and TRAF-C domains. Consistent with the paradigm described, expression of LP1 TRAF3 in B cells promoted higher basal levels of NF-κB2 activation compared to Wt TRAF3. However, LP1 did not associate with TRAF2, CD40, or BAFFR, and no LP1 degradation was observed following receptor engagement. Interestingly, LP1 showed enhanced NIK association. Thus, TRAF3 degradation becomes dispensable to activate NF-κB2 when it is unable to associate with TRAF2. In a second model, we examined several mutant forms of BAFFR that are unable to induce NF-κB2 activation in B cells. Signaling to B cells by each of these BAFFR mutants, however, induced levels of TRAF3 degradation similar to those induced by Wt BAFFR. Thus, in B cells, receptor-mediated TRAF3 degradation is not sufficient to promote NF-B2 activation. We thus conclude that there is not a simple linear relationship in B lymphocytes between relative levels of cellular TRAF3, induced TRAF3 degradation, NIK activation and NF-B2 activation.

  15. Genetische Analyse des Tyrosinkinase-Rezeptors ErbB2

    OpenAIRE

    Woldeyesus, Masresha Tsegaye

    2001-01-01

    ErbB2 gehört zu den Klasse I Rezeptor-Tyrosinkinasen und funktioniert als Ko-rezeptor bei der Vermittlung des Neuregulin-Signals. Während der Embryonal-entwicklung wird ErbB2 im Herzen, in den Neuralleistenzellen, im Muskel und in den Epithelien exprimiert (Kokai et al. 1987). Embryonen mit einer Null-Mutation im ErbB2 Gen sterben am Tag 10,5 der Embryonalentwicklung. Die Mutation bewirkt eine morphogenetische Fehlbildung des Herzens, die durch das Fehlen von ventrikulären Trabekeln gekennzei...

  16. B2B营销的权威

    Institute of Scientific and Technical Information of China (English)

    陈荣

    2006-01-01

    现在很流行的一个词就是B2B营销,那么到底什么叫B2B营销呢?雷·赖特所著的《组织间营销》(英文全名Business—to—Business Marketing:AStep-by-Step Guide)可以回答你的问题,它可谓是全面了解B2B营销所涉及的各个层面的权威书籍。

  17. Sosiaalisen median strategia B2B-yritykselle

    OpenAIRE

    Johansson, Mia

    2013-01-01

    Opinnäytetyössä perehdyttiin sosiaaliseen mediaan ja sen hyödyntämiseen B2B-näkökulmasta. Opinnäytetyön tarkoitus oli selvittää, miten B2B-yritys voi hyödyntää sosiaalista mediaa osana liiketoimintaansa ja miten sosiaalisen median strategia käytännössä toteutetaan. Työn aikana opinnäytetyön tekijä oli osana sosiaalisen median strategian suunnittelua ja valmistumista case-yrityksessä. Case-yritys on oululainen informaatioteknologian alalla toimiva B2B-yritys. Sosiaalisen median avulla...

  18. B2B virksomheders brug af sociale medier

    OpenAIRE

    Persdatter Gotfredsen, Karoline

    2016-01-01

    Purpose: The aim of this master thesis is to explore how B2B firms perceive their own usage of social media to establish and strengthen successful relational exchanges. Approach: In-depth interviews were carried out with three key informants responsible for social media marketing at large B2B firms. The findings from the three interviews were then analysed case-by-case and finally a cross case analysis was conducted. Findings: In relation to the market B2B firms mainly see social media...

  19. Digitaalisen markkinoinnin suunnitelma b2b-yritykselle

    OpenAIRE

    Harhakoski, Oskari

    2011-01-01

    Työ käsittelee digitaalisen markkinoinnin suunnitelman tekemistä b2b-yritykselle. Tavoitteena oli kilpailuedun hankkiminen sosiaalisen median tehokkaalla hyödyntämisellä mark-kinoinnissa. Konkreettisemmin yritys halusi lisää näkyvyyttä ja myyntiä. Suunnitelman laatimisessa hyödynnettiin POST-menetelmää. Erityistä huomiota kiinnitettiin b2b-markkinoinnin eroihin b2c-markkinointiin verrattuna. Myös yrityksen toimiminen Suomen markkinoilla huomioitiin. Lisäksi analysoitiin kilpailijoita asia...

  20. Pulse laser irradiation into superconducting MgB2 detector

    International Nuclear Information System (INIS)

    We performed 20-ps pulse laser irradiation experiments on a MgB2 neutron detector to know a thermal-relaxation process for designing a MgB2 neutron detector. The membrane-type structured MgB2 device was fabricated to minimize the heat capacity of sensing part of a detector as well as to enhance its sensitivity. We successfully observed a thermal-relaxation signal resulting from pulse laser irradiation by developing a detection circuit. The response time was faster than 1 μs, meaning that the detector would be capable of counting neutrons at a rate of more than 106 events per second

  1. Ultrasonic Properties of the MgB2 Superconductor

    Institute of Scientific and Technical Information of China (English)

    YU Ri-Cheng; JIN Chang-Qing; LI Shao-Chun; WANG Ru-Ju; LI Feng-Ying; LIU Zhen-Xing; ZHU Jia-Lin

    2001-01-01

    The sound velocities of longitudinal and shear waves are measured on a polycrystalline MgB2 superconductor with Tc of 39 K. The specimen used in the experiments is pressed and heated using the MgB2 powder. The elastic moduli, Debye temperature and specific heat at room temperature are obtained based on sound velocity data. The results indicate that the velocities are much higher than those in the usual materials, while elastic constants remain reasonably soft, which may be due to the high transition temperature of the MgB2 superconductor.

  2. Bowman-Birk Protease Inhibitor from Vigna unguiculata Seeds Enhances the Action of Bradykinin-Related Peptides

    Directory of Open Access Journals (Sweden)

    Alice da Cunha M. Álvares

    2014-10-01

    Full Text Available The hydrolysis of bradykinin (Bk by different classes of proteases in plasma and tissues leads to a decrease in its half-life. Here, Bk actions on smooth muscle and in vivo cardiovascular assays in association with a protease inhibitor, Black eyed-pea trypsin and chymotrypsin inhibitor (BTCI and also under the effect of trypsin and chymotrypsin were evaluated. Two synthetic Bk-related peptides, Bk1 and Bk2, were used to investigate the importance of additional C-terminal amino acid residues on serine protease activity. BTCI forms complexes with Bk and analogues at pH 5.0, 7.4 and 9.0, presenting binding constants ranging from 103 to 104 M−1. Formation of BTCI-Bk complexes is probably driven by hydrophobic forces, coupled with slight conformational changes in BTCI. In vitro assays using guinea pig (Cavia porcellus ileum showed that Bk retains the ability to induce smooth muscle contraction in the presence of BTCI. Moreover, no alteration in the inhibitory activity of BTCI in complex with Bk and analogous was observed. When the BTCI and BTCI-Bk complexes were tested in vivo, a decrease of vascular resistance and consequent hypotension and potentiating renal and aortic vasodilatation induced by Bk and Bk2 infusions was observed. These results indicate that BTCI-Bk complexes may be a reliable strategy to act as a carrier and protective approach for Bk-related peptides against plasma serine proteases cleavage, leading to an increase in their half-life. These findings also indicate that BTCI could remain stable in some tissues to inhibit chymotrypsin or trypsin-like enzymes that cleave and inactivate bradykinin in situ.

  3. Bowman-Birk protease inhibitor from Vigna unguiculata seeds enhances the action of bradykinin-related peptides.

    Science.gov (United States)

    da Cunha Morales Álvares, Alice; Schwartz, Elisabeth Ferroni; Amaral, Nathalia Oda; Trindade, Neidiane Rosa; Pedrino, Gustavo Rodrigues; Silva, Luciano Paulino; de Freitas, Sonia Maria

    2014-01-01

    The hydrolysis of bradykinin (Bk) by different classes of proteases in plasma and tissues leads to a decrease in its half-life. Here, Bk actions on smooth muscle and in vivo cardiovascular assays in association with a protease inhibitor, Black eyed-pea trypsin and chymotrypsin inhibitor (BTCI) and also under the effect of trypsin and chymotrypsin were evaluated. Two synthetic Bk-related peptides, Bk1 and Bk2, were used to investigate the importance of additional C-terminal amino acid residues on serine protease activity. BTCI forms complexes with Bk and analogues at pH 5.0, 7.4 and 9.0, presenting binding constants ranging from 103 to 104 M-1. Formation of BTCI-Bk complexes is probably driven by hydrophobic forces, coupled with slight conformational changes in BTCI. In vitro assays using guinea pig (Cavia porcellus) ileum showed that Bk retains the ability to induce smooth muscle contraction in the presence of BTCI. Moreover, no alteration in the inhibitory activity of BTCI in complex with Bk and analogous was observed. When the BTCI and BTCI-Bk complexes were tested in vivo, a decrease of vascular resistance and consequent hypotension and potentiating renal and aortic vasodilatation induced by Bk and Bk2 infusions was observed. These results indicate that BTCI-Bk complexes may be a reliable strategy to act as a carrier and protective approach for Bk-related peptides against plasma serine proteases cleavage, leading to an increase in their half-life. These findings also indicate that BTCI could remain stable in some tissues to inhibit chymotrypsin or trypsin-like enzymes that cleave and inactivate bradykinin in situ. PMID:25361421

  4. Thermal shock resistance of ZrB2 and ZrB2-30% SiC

    International Nuclear Information System (INIS)

    Thermal shock of high density (>99% relative density) zirconium diboride (ZrB2) and zirconium diboride containing 30 vol.% silicon carbide (SiC) was studied. Calculations based on thermal shock theory indicated that ZrB2-30 vol.% SiC should have greater thermal shock resistance than ZrB2 due to its higher fracture strength. Water quench tests revealed essentially the same critical thermal shock values for both materials (ΔTcrit = ∼400 deg. C). A finite element model was used to estimate the temperatures and stresses in both ceramics during quench testing. The model predicted that maximum thermal stresses during the experimental quench test exceeded the strength of ZrB2 (568 MPa) but not ZrB2-30 vol.% SiC (863 MPa). The lower than predicted thermal shock resistance of ZrB2-SiC was attributed to the non-uniform cooling between the ZrB2 matrix grains and the SiC particulate phase

  5. Structural stability and electrical properties of AlB2-type MnB2 under high pressure

    International Nuclear Information System (INIS)

    The structural stability and electrical properties of AlB2-type MnB2 were studied based on high pressure angle-dispersive x-ray diffraction, in situ electrical resistivity measured in a diamond anvil cell (DAC) and first-principles calculations under high pressure. The x-ray diffraction results show that the structure of AlB2-type MnB2 remains stable up to 42.6 GPa. From the equation of state of MnB2, we obtained a bulk modulus value of 169.9±3.7 GPa with a fixed pressure derivative of 4, which indicates that AlB2-type MnB2 is a hard and incompressible material. The electrical resistance undergoes a transition at about 19.3 GPa, which can be explained by a transition of manganese 3d electrons from localization to delocalization under high pressure. (condensed matter: structural, mechanical, and thermal properties)

  6. miR-204 downregulates EphB2 in aging mouse hippocampal neurons.

    Science.gov (United States)

    Danka Mohammed, Chand Parvez; Rhee, Hwanseok; Phee, Bong-Kwan; Kim, Kunhyung; Kim, Hee-Jin; Lee, Hyehyeon; Park, Jung Hoon; Jung, Jung Hee; Kim, Jeong Yeon; Kim, Hyoung-Chin; Park, Sang Ki; Nam, Hong Gil; Kim, Keetae

    2016-04-01

    Hippocampal synaptic function and plasticity deteriorate with age, often resulting in learning and memory deficits. As MicroRNAs (miRNAs) are important regulators of neuronal protein expression, we examined whether miRNAs may contribute to this age-associated decline in hippocampal function. We first compared the small RNA transcriptome of hippocampal tissues from young and old mice. Among 269 hippocampal miRNAs, 80 were differentially expressed (≥ twofold) among the age groups. We focused on 36 miRNAs upregulated in the old mice compared with those in the young mice. The potential targets of these 36 miRNAs included 11 critical Eph/Ephrin synaptic signaling components. The expression levels of several genes in the Eph/Ephrin pathway, including EphB2, were significantly downregulated in the aged hippocampus. EphB2 is a known regulator of synaptic plasticity in hippocampal neurons, in part by regulating the surface expression of the NMDA receptor NR1 subunit. We found that EphB2 is a direct target of miR-204 among miRNAs that were upregulated with age. The transfection of primary hippocampal neurons with a miR-204 mimic suppressed both EphB2 mRNA and protein expression and reduced the surface expression of NR1. Transfection of miR-204 also decreased the total expression of NR1. miR-204 induces senescence-like phenotype in fully matured neurons as evidenced by an increase in p16-positive cells. We suggest that aging is accompanied by the upregulation of miR-204 in the hippocampus, which downregulates EphB2 and results in reduced surface and total NR1 expression. This mechanism may contribute to age-associated decline in hippocampal synaptic plasticity and the related cognitive functions. PMID:26799631

  7. Bending strain tolerance of MgB2 superconducting wires

    Science.gov (United States)

    Kováč, P.; Hušek, I.; Melišek, T.; Kulich, M.; Kopera, L.

    2016-04-01

    This work describes the strain tolerance of MgB2 superconductors subjected to variable bending stresses. Bending of MgB2 wire was done at room temperature in different modes: (i) direct bending of straight annealed samples to variable diameters and by (ii) indirect bending by straightening of bent and annealed samples. I c-bending strain characteristics of samples made by in situ PIT and by the internal magnesium diffusion (IMD) process were measured at 4.2 K. The results show a good agreement between the direct and indirect bending mode, which allows easier estimation of limits important for the winding process of MgB2 superconductors with brittle filaments. A comparison of MgB2 wires made by in situ PIT and IMD processes showed improved strain tolerance for IMD due to better grain connectivity the low annealing temperature, which does not appear to reduce the mechanical strength of sheath material.

  8. Thromboxane B2 formation in patients with acute myocardial infarction

    International Nuclear Information System (INIS)

    Thromboxane A2 is a stable metabolite of thromboxane B2 which production and release were reported with many of the risk factors related to coronary-artery disease. In 18 patients with acute transmural myocardial infarction serial determinations of thromboxane B2 were performed in the blood having clotted at 370C for 30 min. Significantly less (p < 0.05) of thromboxane B2 was formed in the first week after infarction compared to the control group. Thromboxane B 2 formed in the blood of these patients increased slightly in the recovery period but was still lower than in healthy population. Since thromboxane A2 exerts deleterious effects upon myocardial performance an adaptive protective effect of the decreased thromboxane synthesis in patients with myocardial infarction was suggested. (orig.)

  9. Applying conceptual design to B2B sales negotiations

    DEFF Research Database (Denmark)

    Illi, Mikko; Ylirisku, Salu

    This paper addresses the challenge of perceiving B2B sales negotiation in a manner that would open up new possibilities for the improvement of the practice. B2B sales agents work under high pressure in developing relevant and appealing proposals when negotiating for a deal with a customer. The key...... problem that will be addressed is the building of understanding of a customer’s current needs and requirements, and then trying to devise an appropriate proposal to match these. The work of the sales agents in B2B sales negotiations is highly complex, as they need to understand both the modular machinery...... the ways in which design sense making artefacts may drive also B2B sales agents’ work....

  10. B2B“风口”渐近

    Institute of Scientific and Technical Information of China (English)

    杨宁

    2014-01-01

    经过十多年的发展,B2B业务在2014年有一种“风口”的感觉。经过十多年的发展,B2B在2014年有一种“风口”的感觉。2009-2013年,B2B交易额和市场收入差异非常大:包括阿里巴巴、慧聪网等总收入不到200亿元,而中国B2B市场的交易规模在7万~8万亿之间。

  11. Preparation of MgB2 superconducting tapes using electrophoresis

    Science.gov (United States)

    Xu, J. D.; Wang, S. F.; Zhou, Y. B.; Zhou, Y. L.; Chen, Z. H.; Cui, D. F.; Lu, H. B.; He, M.; Dai, S. Y.; Yang, G. Z.

    2002-08-01

    Superconducting MgB2/Ta tapes with a critical temperature of 34 K have been prepared successfully by ex situ annealing of electrophoresis-grown boron in the presence of Mg vapour at 920 °C. Scanning electron microscopy was used to examine the surface morphology of the MgB2/Ta tapes, and well-formed MgB2 crystals with sizes up to 2 μm were observed. The x-ray diffraction patterns showed randomly orientated growth of MgB2 phase in the tapes. Estimates using hysteresis loops and the Bean model give a value of 6.8 × 105 A cm-2 for the critical current density.

  12. Fabrication of sandwich-type MgB2/Boron/MgB2 Josephson junctions with rapid annealing method

    International Nuclear Information System (INIS)

    Sandwich-type MgB2/Boron/MgB2 Josephson junctions were fabricated using magnetron sputtering system. The rapid-anneal process was adopted to replace traditional way of annealing, trying to solve the problem of interdiffusion and oxidation with multilayer films. The boron film was used as barrier layer to avoid the introduction of impurities and improve reproducibility of the junctions. The bottom MgB2 thin films deposited on c-plane sapphire substrate exhibits a critical temperature TC of 37.5 K and critical current density JC at 5 K of 8.7 × 106 A cm−2. From the XRD pattern, the bottom MgB2 thin film shows c-axis orientation, whereas the top MgB2 became polycrystalline as Boron barrier layer grown thicker. Therefore, all junction samples show lower TC than single MgB2 thin film. The junctions exhibit excellent quasiparticle characteristics with ideal dependence on temperature and Boron barrier thickness. Subharmonic gap structure was appeared in conductance characteristics, which was attributed to the multiple Andreev reflections (MAR). The result demonstrates great promise of this new fabrication technology for MgB2 Josephson junction fabrication. - Highlights: • Sandwich-type MgB2/Boron/MgB2 Josephson junctions were fabricated. • The junctions were annealed after deposition with the rapid-anneal process. • The highest critical current is 25.3 mA at 5 K and remains non-zero near 25 K. • Subharmonic gap features can be observed in the dI/dV – V curves

  13. Scope of Internal Marketing in B2B Companies

    OpenAIRE

    Nigam, Niharika

    2007-01-01

    Abstract Previous studies have focused on "internal marketing" from services marketing perspective. There is, therefore, a great dearth of in-depth research on its application to other business types. This research attempts to find the scope of internal marketing in B2B companies. The purpose of this research is to closely examine the elements, their linkage, tools and applications of Internal marketing when applied to B2B settings. Internal marketing, the application of marketing managem...

  14. Preparation and characterization of MgB2 superconductor

    Indian Academy of Sciences (India)

    Shashwati Sen; D K Aswal; Ajay Singh; T V Chandrasekhar Rao; K P Muthe; J C Vyas; L C Gupta; S K Gupta; V C Sahni

    2002-05-01

    The MgB2 superconductor, synthesized using solid-state and liquid-phase sintering methods, have been characterized for various properties. The upper critical field, irreversibility line and critical current density have been determined using magnetization data. The current–voltage characteristics recorded under an applied magnetic field revealed the existence of vortex glass transition. The surface analysis using X-ray photoelectron spectroscopy shows that MgB2 is sensitive to atmospheric degradation.

  15. TiB2 ceramic and DLC Multilayered PVD coatings

    OpenAIRE

    Santos da Silva Cruz, Ricardo Manuel

    2007-01-01

    Titanium diboride (TiB2) has been investigated as a potential candidate for several industrial applications, such as: cutting tools, electric devices, wear parts and many more fields of application. The main drawback of TiB2 is its brittle nature, which has limited its range of applications. Diamond-like Carbon (DLC) has been used in industrial applications, mainly for wear resistant parts. However, the application of DLC films has been limited by the level of internal stres...

  16. Branding of electricity in B2B markets

    OpenAIRE

    Rolanda Simenaite 1986

    2013-01-01

    Branding has gained an important role in the B2B (business-to-business) market. Liberation of the energy markets in recent years has increased competition and branding could create a competitive advantage. This thesis analyzes the branding of electricity in a business-to-business context. In depth, this thesis explores the supplier of electricity brand importance for business customers in both Icelandic and Lithuanian B2B markets. The focus of the thesis is to research how much brands matter ...

  17. POLICY CONCERNS FOR ONLINE B2B EXCHANGES

    OpenAIRE

    Hooker, Neal H.; Rha, Jong-Youn; Ernst, Stanley C.; Widdows, Richard

    2002-01-01

    Policy concerns arise as e-business activities become increasingly common. This paper discusses important elements of such concerns, particularly the pro- and anti-competitive assessment of online business-to-business (B2B) exchanges. The definition of markets, the role of quality management and communication, and join purchasing implications within such environments are related to food distribution systems. Other online business-to-consumer (B2C) and consumer-to-business (C2B) policy concern...

  18. B2B品牌的隐形价值

    Institute of Scientific and Technical Information of China (English)

    詹姆斯·格雷戈里; 唐纳德·塞克斯顿

    2007-01-01

    @@ 消费品营销人员满脑子想着品牌资产(brand equity),他们也理应如 此.B2B公司如能效法,将是明智之举.我们对450多家公司进行了16年的量化研究,结果表明B2B品牌蕴藏着数十亿美元的价值.

  19. B2B emarketplace announcements and shareholder wealth

    OpenAIRE

    Andrew H. Chen; Siems, Thomas F.

    2001-01-01

    In the business-to-business (B2B) sector, new supply-chain models within electronic marketplaces (eMarketplaces) offer firms significantly lower procurement costs, increased operating efficiencies, and expanded market opportunities. Using event-study methodology to look at the period July 1999-March 2000, Andrew Chen and Thomas Siems find that investors reacted favorably to B2B eMarketplace announcements, with slightly higher abnormal returns associated with vertical than with horizontal eMar...

  20. ZrB2 and HfB2 toughened with Hi Nicalon SiC chopped fibers

    OpenAIRE

    Silvestroni, Laura; Sciti, Diletta

    2012-01-01

    ZrB2 and HfB2 are candidate materials for use in aggressive environment, owing a unique combination of favourable properties of high temperature stability and excellent engineeristic properties. This class of materials is raising always more interest for future generation space vehicles, as wing leading edges and nose tips, as well as propulsion system elements. The most investigated system is based on ZrB2-SiC, owing to a high strength, up to 1 GPa, high hardness, around 20 GPa and oxidation...

  1. Il B2B e il paradigma dei costi di transazione (B2B and the Transaction Costs Paradigm

    Directory of Open Access Journals (Sweden)

    Pierluigi Sabbatini

    2001-06-01

    Full Text Available Business to Business (B2B Internet commerce causes a significant contraction of transaction costs. According to the Coase paradigm, we would thus expect a deverticalization of the industry and broader scope for anonymous market mechanisms. In reality, such expectations are not fully borne out by the facts. When the industrial structure is concentrated the B2Bgenerally loses its independence, and is owned by the firms which most contribute to its development, e.g. the ones able to bring the liquidity to it. The B2B governance mechanism established by these firms gives hierarchical mechanisms a role which they do not usually play in extensive, anonymous markets.

  2. Mechanical and thermal properties of bulk ZrB2

    Science.gov (United States)

    Nakamori, Fumihiro; Ohishi, Yuji; Muta, Hiroaki; Kurosaki, Ken; Fukumoto, Ken-ichi; Yamanaka, Shinsuke

    2015-12-01

    ZrB2 appears to have formed in the fuel debris at the Fukushima Daiichi nuclear disaster site, through the reaction between Zircaloy cladding materials and the control rod material B4C. Since ZrB2 has a high melting point of 3518 K, the ceramic has been widely studied as a heat-resistant material. Although various studies on the thermochemical and thermophysical properties have been performed for ZrB2, significant differences exist in the data, possibly due to impurities or the porosity within the studied samples. In the present study, we have prepared a ZrB2 bulk sample with 93.1% theoretical density by sintering ZrB2 powder. On this sample, we have comprehensively examined the thermal and mechanical properties of ZrB2 by the measurement of specific heat, ultrasonic sound velocities, thermal diffusivity, and thermal expansion. Vickers hardness and fracture toughness were also measured and found to be 13-23 GPa and 1.8-2.8 MPa m0.5, respectively. The relationships between these properties were carefully examined in the present study.

  3. Superconductivity in Dense MgB2 Wires

    International Nuclear Information System (INIS)

    MgB2 becomes superconducting just below 40K. Whereas porous polycrystalline samples of MgB2 can be synthesized from boron powders, in this Letter we demonstrate that dense wires of MgB2 can be prepared by exposing boron filaments to Mg vapor. The resulting wires have a diameter of 160 μm , are better than 80% dense, and manifest the full χ=-1/4π shielding in the superconducting state. Temperature-dependent resistivity measurements indicate that MgB2 is a highly conducting metal in the normal state with ρ(40 K)=0.38 μΩcm . By using this value, an electronic mean-free path, l∼600 angstrom can be estimated, indicating that MgB2 wires are well within the clean limit. Tc , Hc2(T) , and Jc data indicate that MgB2 manifests comparable or better superconducting properties in dense wire form than it manifests as a sintered pellet

  4. Thermal stability of hexagonal OsB2

    International Nuclear Information System (INIS)

    The synthesis of novel hexagonal ReB2-type OsB2 ceramic powder was performed by high energy ball milling of elemental Os and B powders. Two different sources of B powder have been used for this mechanochemical synthesis. One B powder consisted of a mixture of amorphous and crystalline phases and a mixture of 10B and 11B isotopes with a fine particle size, while another B powder was a purely crystalline (rhombohedral) material consisting of enriched 11B isotope with coarse particle size. The same Os powder was used for the synthesis in both cases. It was established that, in the first case, the hexagonal OsB2 phase was the main product of synthesis with a small quantity of Os2B3 phase present after synthesis as an intermediate product. In the second case, where coarse crystalline 11B powder was used as a raw material, only Os2B3 boride was synthesized mechanochemically. The thermal stability of hexagonal OsB2 powder was studied by heating under argon up to 876 °C and cooling in vacuo down to −225 °C. During the heating, the sacrificial reaction 2OsB2+3O2→2Os+2B2O3 took place due to presence of O2/water vapor molecules in the heating chamber, resulting in the oxidation of B atoms and formation of B2O3 and precipitation of Os metal out of the OsB2 lattice. As a result of such phase changes during heating, the lattice parameters of hexagonal OsB2 changed significantly. The shrinkage of the a lattice parameter was recorded in 276–426 °C temperature range upon heating, which was attributed to the removal of B atoms from the OsB2 lattice due to oxidation followed by the precipitation of Os atoms and formation of Os metal. While significant structural changes occurred upon heating due to presence of O2, the hexagonal OsB2 ceramic demonstrated good phase stability upon cooling in vacuo with linear shrinkage of the lattice parameters and no phase changes detected during cooling. - Graphical abstract: The in situ high temperature XRD contour plot (A) and XRD patterns

  5. 111In-labeled KCCYSL peptide as an imaging probe for ErbB-2-expressing ovarian carcinomas

    OpenAIRE

    Deutscher, Susan L.; Figueroa, Said D.; Kumar, Senthil R.

    2009-01-01

    Aberrant expression of ErbB-2, a member of the epidermal growth factor family of receptors, has been implicated in the formation of various malignancies including ovarian cancer. The objective of this study was to determine if the bacteriophage (phage) display-selected ErbB-2 targeting peptide, KCCYSL, once radiolabeled with 111In would serve as a tumor targeting and Single Photon Emission Computed Tomography (SPECT/CT) imaging agent in a mouse model of human ovarian carcinoma expressing ErbB...

  6. Vascular endothelium receptors and transduction mechanisms

    CERN Document Server

    Gillis, C; Ryan, Una; Proceedings of the Advanced Studies Institute on "Vascular Endothelium: Receptors and Transduction Mechanisms"

    1989-01-01

    Beyond their obvious role of a barrier between blood and tissue, vascular endothelial cells are now firmly established as active and essential participants in a host of crucial physiological and pathophysiological functions. Probably the two most important factors responsible for promoting the current knowledge of endothelial functions are 1) observations in the late sixties-early seventies that many non-ventilatory properties of the lung could be attributed to the pulmonary endothelium and 2) the establishment, in the early and mid-seventies of procedures for routine culture of vascular endothelial cells. Many of these endothelial functions require the presence of receptors on the surface of the plasma membrane. There is now evidence for the existence among others of muscarinic, a-and /3-adrenergic, purine, insulin, histamine, bradykinin, lipoprotein, thrombin, paf, fibronectin, vitronectin, interleukin and albumin receptors. For some of these ligands, there is evidence only for the existence of endothelial ...

  7. Ethanol Enhances the Interaction of Breast Cancer Cells Over-Expressing ErbB2 With Fibronectin

    Science.gov (United States)

    Xu, Mei; Bower, Kimberly A.; Chen, Gang; Shi, Xianglin; Dong, Zheng; Ke, Zunji; Luo, Jia

    2016-01-01

    Background Ethanol is a tumor promoter and may enhance the metastasis of breast cancer. However, the underlying cellular / molecular mechanisms remain unknown. Amplification of ErbB2 or HER2, a receptor tyrosine kinase of the ErbB family, is found in 20 to 30% of patients with breast cancer. We have previously demonstrated that the effect of ethanol on the migration / invasion of breast cancer cells positively correlated with the expression levels of ErbB2. Adhesion to the extracellular matrix (ECM) is an important initial step for cancer cell invasion and metastasis. In this study, we investigated the effects of ethanol on the adhesion of MCF7 breast cancer cells over-expressing ErbB2 (MCF7ErbB2) to human plasma fibronectin. Methods To test the hypothesis that ethanol may enhance the attachment of human breast cancer cells to fibronectin, an important component of the ECM, we evaluated the effect of ethanol on the expression of focal adhesions, cell attachment, and ErbB2 signaling in cultured MCF7ErbB2 cells. Results Exposure to ethanol drastically enhanced the adhesion of MCFErbB2 cells to fibronectin and increased the expression of focal adhesions. Ethanol induced phosphorylation of ErbB2 at Tyr1248, FAK at Tyr861, and cSrc at Try216. Ethanol promoted the interaction among ErbB2, FAK, and cSrc, and the formation of a focal complex. AG825, a selective ErbB2 inhibitor, attenuated the ethanol-induced phosphorylation of ErbB2 and its association with FAK. Furthermore, AG825 blocked ethanol-promoted cell / fibronectin adhesion as well as the expression of focal adhesions. Conclusions Our results suggest that ethanol enhances the adhesion of breast cancer cells to fibronectin in an ErbB2-dependent manner, and the FAK pathway plays an important role in ethanol-induced formation of a focal complex. PMID:20201928

  8. Mechanical-thermal synthesis of NbB2 powder from Mg/B2O3/Nb powder mixture

    International Nuclear Information System (INIS)

    Three different approaches were used for the synthesis of niobium boride using a stoichiometric ratio of Mg-B2O3-Nb powder mixture: (i) thermal ignition, (ii) mechanochemical and (iii) a combined mechanical and thermal activation process. Phase transformation analysis and structural evaluation were carried out by means of differential thermal analysis techniques, X-ray diffractometry, scanning electron microscopy and transmission electron microscopy. During the thermal synthesis, the reaction between Mg and B2O3 partially occurred (liquid state reaction). The desired final phase (NbB2) was poorly obtained. Phase analysis revealed that the NbB2 phase was synthesized after 10 h of high energy ball milling. A pre-milling treatment of the powder mixture up to 2 h significantly reduced the reactions temperature (580 C). Consequently, NbB2 was prepared simultaneously involving magnesiothermic reduction of B2O3 and reaction between elemental of Nb and boron. Mg3(BO3)2, as major by-product, was formed in noticeable amounts during the thermal process, while its quantity significantly decreased during mechanochemical synthesis and completely eliminated by using the combined mechanical and thermal synthesis.

  9. Non-resonant microwave absorption studies of superconducting MgB2 and MgB2 + MgO

    Indian Academy of Sciences (India)

    Janhavi P Joshi; Subhasis Sarangi; A K Sood; Dilip Pal; S V Bhat

    2002-02-01

    Non-resonant microwave absorption (NRMA) studies of superconducting MgB2 and a sample containing ∼ 10% by weight of MgO in MgB2 are reported. The NRMA results indicate near absence of intergranular weak links in the pure MgB2 sample. A linear temperature dependence of the lower critical field c1 is observed indicating a non- wave superconductivity. However, the phase reversal of the NRMA signal which could suggest wave symmetry is also not observed. In the MgB2 + MgO sample, much larger low field dependent absorption is observed indicating the presence of intergranular weak links. The hysteretic behavior of NRMA is compared and contrasted in the two samples. In the pure MgB2 sample, a large hysteresis is observed between the forward and the reverse scans of the magnetic field indicating strong pinning of flux lines. This hysteresis saturates a few degrees below c while in the MgB2 + MgO sample, a much slower increase of hysteresis with decreasing temperature is observed, a signature of weaker pinning.

  10. The compressibility of high purity YbB2.

    Science.gov (United States)

    Kalkan, B; Suzer, S; Ozdas, E

    2012-08-29

    The compressibility and phase stability of Y bB(2) are investigated under high pressure using high-resolution synchrotron x-ray diffraction in a diamond anvil cell. The bulk modules of high purity Y bB(2) is obtained as ∼182 GPa using the Birch-Murnaghan equation of state. The patterns measured up to 20 GPa and the pressure dependence of normalized lattice parameters, a/a(0) and c/c(0), reveal that the compressibility of Y bB(2) is low and fairly isotropic, and this material can be classified as a hard material. X-ray photoemission studies demonstrate that Yb in Y bB(2) has a mostly trivalent valence state at room temperature. Moreover, sample preparation details provide a new insight into the high purity synthesis of Y bB(2) at ambient pressure and moderate temperatures. The presented structural and compressibility results are in agreement with the available theoretical and experimental data on binary rare-earth borides and can serve as a reliable reference for future studies. PMID:22850355

  11. Islet-activating protein inhibits leukotriene D4- and leukotriene C4- but not bradykinin- or calcium ionophore-induced prostacyclin synthesis in bovine endothelial cells.

    OpenAIRE

    Clark, M. A.; Conway, T.M.; Bennett, C F; Crooke, S T; Stadel, J M

    1986-01-01

    Incubation of the bovine endothelial cell line, CPAE, with leukotriene D4, leukotriene C4, bradykinin, or the calcium ionophore A23187 results in the release of arachidonic acid metabolites including 6-keto-prostaglandin F1 alpha, the stable metabolite of prostacyclin. Pretreatment of these cells with the pertussis toxin islet-activating protein (IAP) results in a dose-dependent inhibition of the release of arachidonic acid metabolites and prostacyclin in response to leukotriene D4 and leukot...

  12. Identification of bradykinin: related peptides from Phyllomedusa nordestina skin secretion using electrospray ionization tandem mass spectrometry after a single-step liquid chromatography

    OpenAIRE

    K Conceição; FM Bruni; JM Sciani; Konno, K; RL Melo; MM Antoniazzi; C Jared; M Lopes-Ferreira; DC Pimenta

    2009-01-01

    Amphibian skin secretions are a source of potential new drugs with medical and biotechnological applications. Rich in peptides produced by holocrine-type serous glands in the integument, these secretions play different roles, either in the regulation of physiological skin functions or in the defense against predators or microorganisms. The aim of the present work was to identify novel peptides with bradykinin-like structure and/or activity present in the skin of Phyllomedusa nordestina. In or...

  13. Myocilin mediates myelination in the peripheral nervous system through ErbB2/3 signaling.

    Science.gov (United States)

    Kwon, Heung Sun; Johnson, Thomas V; Joe, Myung Kuk; Abu-Asab, Mones; Zhang, Jun; Chan, Chi Chao; Tomarev, Stanislav I

    2013-09-13

    The glaucoma-associated gene, myocilin, is expressed in ocular and non-ocular tissues including the peripheral nervous system, but its functions in these tissues remain poorly understood. We demonstrate that in sciatic nerve, myocilin is expressed in Schwann cells with high concentrations at the nodes of Ranvier. There, myocilin interacts with gliomedin, neurofascin, and NrCAM, which are essential for node formation and function. Treatment of isolated dorsal root ganglion cultures with myocilin stimulates clustering of the nodal proteins neurofascin and sodium channel Nav1.2. Sciatic nerves of myocilin null mice express reduced levels of several myelin-associated and basal membrane proteins compared with those of wild-type littermates. They also demonstrate reduced myelin sheath thickness and partial disorganization of the nodes. Myocilin signaling through ErbB2/3 receptors may contribute to these observed effects. Myocilin binds to ErbB2/ErbB3, activates these receptors, and affects the downstream PI3K-AKT signaling pathway. These data implicate a role for myocilin in the development and/or maintenance of myelination and nodes of Ranvier in sciatic nerve. PMID:23897819

  14. EBSD analysis of MgB2 bulk superconductors

    Science.gov (United States)

    Koblischka-Veneva, A.; Koblischka, M. R.; Schmauch, J.; Inoue, K.; Muralidhar, M.; Berger, K.; Noudem, J.

    2016-04-01

    The grain orientation, the texture and the grain boundary misorientations are important parameters for the understanding of the magnetic properties of the bulk MgB2 samples intended for super-magnet applications. Such data can be provided by electron backscatter diffraction (EBSD) analysis. However, as the grain size (GS) of the MgB2 bulks is preferably in the 100-200 nm range, the common EBSD technique working in reflection operates properly only on highly dense samples. In order to achieve a reasonably good Kikuchi pattern quality on all samples, we apply here the newly developed transmission EBSD (t-EBSD) technique to several bulk MgB2 samples. This method requires the preparation of TEM slices by means of focused ion-beam milling, which are then analyzed within the SEM, operating with a specific sample holder. We present several EBSD mappings of samples prepared with different techniques and at various reaction temperatures.

  15. Percolative superconductivity in Mg1-xB2

    International Nuclear Information System (INIS)

    Our results from various transport experiments on Mg1-xB2 indicate a surprising effect associated with the presence of a Mg deficiency in MgB2: the phase separation between Mg-vacancy rich and Mg-vacancy poor phases. The Mg-vacancy poor phase is superconducting, but the insulating nature of the Mg-vacancy rich phase probably originates from the Anderson (disorder-induced) localization of itinerant carriers. Furthermore, electron diffraction measurements indicate that within vacancy-rich regions these defects tend to order with intriguing patterns. This electronic phase separation in Mg1-xB2 shows similar, but also distinct characteristics compared with that observed in La2CuO4+δ

  16. MgB2 superconducting wires basics and applications

    CERN Document Server

    2016-01-01

    The compendium gives a complete overview of the properties of MgB2 (Magnesium Diboride), a superconducting compound with a transition temperature of Tc = 39K, from the fundamental properties to the fabrication of multifilamentary wires and to the presentation of various applications. Written by eminent researchers in the field, this indispensable volume not only discusses superconducting properties of MgB2 compounds, but also describes known preparation methods of thin films and of bulk samples obtained under high pressure methods. A unique selling point of the book is the detailed coverage of various applications based on MgB2, starting with MRI magnets and high current cables, cooled by Helium (He) vapor. High current cables cooled by liquid hydrogen are also highlighted as an interesting alternative due to the shrinking He reserves on earth. Other pertinent subjects comprise permanent magnets, ultrafine wires for space applications and wind generator projects.

  17. Expanding Interprofessional EHR Data in i2b2.

    Science.gov (United States)

    Westra, Bonnie L; Christie, Beverly; Johnson, Steven G; Pruinelli, Lisiane; LaFlamme, Anne; Park, Jung In; Sherman, Suzan G; Byrne, Matthew D; Ranallo, Piper; Speedie, Stuart

    2016-01-01

    Emerging issues of team-based care, precision medicine, and big data science underscore the need for health information technology (HIT) tools for integrating complex data in consistent ways to achieve the triple aims of improving patient outcomes, patient experience, and cost reductions. The purpose of this study was to demonstrate the feasibility of creating a hierarchical flowsheet ontology in i2b2 using data-derived information models and determine the underlying informatics and technical issues. This study is the first of its kind to use information models that aggregate team-based care across time, disciplines, and settings into 14 information models that were integrated into i2b2 in a hierarchical model. In the process of successfully creating a hierarchical ontology for flowsheet data in i2b2, we uncovered a variety of informatics and technical issues described in this paper. PMID:27570680

  18. B2B-verkkokaupan internetmarkkinointi : Case: More On Oy

    OpenAIRE

    Toivonen, Niina; Jesar, Rama

    2012-01-01

    Opinnäytetyön tavoitteena on selvittää, millaiseksi More On Oy B2B-liikelahjayrityksen verkko¬-kaupan internetmarkkinointi pitää suunnitella, jotta uusi verkkokauppa antaa hyvän kuvan yrityksestä. Opinnäytetyö on tehty laadullisin tutkimusmenetelmin ja se on rajattu käsittelemään B2B-verkkokaupan internetmarkkinointia erityisesti toimeksiantajayrityksen näkökulmasta. Opinnäytetyön teoriaosuudessa on kerrottu verkkokaupasta yleisesti sekä verkkokaupan inter-netmarkkinoinnin keinoista. More...

  19. Risk Analysis and Consumer Protection in B2C Transactions

    Institute of Scientific and Technical Information of China (English)

    YANG Jian-zheng; SHI Qi-liang; Gary Millar; Ruhul A. Sarker

    2005-01-01

    Recent studies have shown that the perceived lack of security is a major obstacle to the wider acceptance of e-commerce. To overcome this barrier, businesses need to implement comprehensive consumer protection systems that protect consumers during every stage of the purchasing process. This paper used the consumer behaviour model as the basis for analysing risks in Bussiness-to-Consumer (B2C) transactions. Four categories of risks were identified: information, agreement, payment and delivery risk. By combining these risk categories with the three dimensions of management, technology and legislation, a comprehensive B2C consumer protection framework is developed.

  20. Customized E-Learning for B2B Companies

    Directory of Open Access Journals (Sweden)

    Tim Thomasma

    2014-06-01

    Full Text Available Business-to-Business (B2B companies have customers that are primarily other corporations. These companies have unique problems in workplace training. They must train their customers and their customers’ employees. A B2B company may operate with only a few dozen employees, but they may need to help thousands of customers learn how to make best use of their product or service. Discussions with industry executives suggest an ideal training solution might include a number of features that are reviewed in this paper.

  1. B2B-asiantuntijayritys ja sosiaalinen media

    OpenAIRE

    Sahlman, Katriina

    2012-01-01

    Tämän tutkimuksen tarkoituksena on selvittää, miten B2B-asiantuntijayritykset toimivat sosiaalisessa mediassa, miten ne hyödyntävät sitä palvelujensa ja brändinsä markkinointiin sekä lopulta liiketoimintansa edistämiseen. Tutkimus suoritettiin haastattelumuotoisena, laadullisena tutkimuksena. Tutkimukseen haastateltiin yhdeksää B2B-asiantuntijayrityksissä toimivaa, sosiaalista mediaa työkseen tai sen parissa työskentelevää henkilöä, jotka myös vapaa-ajallaan aktiivisesti käyttävät sosiaal...

  2. Creeping of ZrC-ZrB2 and TiC-TiB2 system alloys at compression

    International Nuclear Information System (INIS)

    The paper is concerned with regularities of high-temperature (1700-2420 deg C) creeping in high-dense fine-grained sintered compositions of the ZrC-ZrB2 and TiC-TiB2 systems. Extremum creeping rate epsilon is determined for alloys with the most developed grain interface (V1:V2=1:1) which for the mentioned system coincides with eutectic compositions. It is shown that nonadditive changes in the creeping rate and a considerable increase in the absolute value of deformation (not less than 30%) in compositions with extremum epsilon as compared with that in individual alloys (5-6%) testify to superplasticity effects in alloys of the mentioned systems. An effect of stress (5-30 MPa) on the epsilon=f(σsup(n)) dependence is studied. It is determined that in alloys of the ZrC-ZrB2 system n>=1 in the TiC-TiB2 system - n>=1.5. It is shown that participation of threshold mechanisms in the mainly intergranular deformation in the TiC-TiB2 system may be related to a possibility for coherent grain boundaries to arise during sintering of disperse powders (d<<0.5 μm)

  3. Quantification of differential ErbB1 and ErbB2 cell surface expression and spatial nanoclustering through plasmon coupling.

    Science.gov (United States)

    Wang, Jing; Yu, Xinwei; Boriskina, Svetlana V; Reinhard, Björn M

    2012-06-13

    Cell surface receptors play ubiquitous roles in cell signaling and communication and their expression levels are important biomarkers for many diseases. Expression levels are, however, only one factor that determines the physiological activity of a receptor. For some surface receptors, their distribution on the cell surface, especially their clustering, provides additional mechanisms for regulation. To access this spatial information robust assays are required that provide detailed insight into the organization of cell surface receptors on nanometer length scales. In this manuscript, we demonstrate through combination of scattering spectroscopy, electron microscopy, and generalized multiple particle Mie theory (GMT) simulations that the density- and morphology-dependent spectral response of Au nanoparticle (NP) immunolabels bound to the epidermal growth factor receptors ErbB1 and ErbB2 encodes quantitative information of both the cell surface expression and spatial clustering of the two receptors in different unliganded in vitro cancer cell lines (SKBR3, MCF7, A431). A systematic characterization of the collective spectral responses of NPs targeted at ErbB1 and ErbB2 at various NP concentrations indicates differences in the large-scale organization of ErbB1 and ErbB2 in cell lines that overexpress these receptors. Validation experiments in the scanning electron microscope (SEM) confirm that NPs targeted at ErbB1 on A431 are more strongly clustered than NPs bound to ErbB2 on SKBR3 or MCF7 at overall comparable NP surface densities. This finding is consistent with the existence of larger receptor clusters for ErbB1 than for ErbB2 in the plasma membranes of the respective cells. PMID:22587495

  4. Bradykinin and vasopressin stimulate Na/sup +/-K/sup +/-Cl/sup -/ cotransport in cultured endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Brock, T.A.; Brugnara, C.; Canessa, M.; Gimbrone, M.A. Jr.

    1986-06-01

    The authors have characterized a Na/sup +/-K/sup +/-Cl/sup -/ cotransporter in vascular endothelial cells (EC) cultured from different blood vessels and species that is inhibited by the diuretics furosemide and bumentanide. Inward /sup 86/Rb influx transported by the Na/sup +/-K/sup +/ pump in cultured EC from bovine and pig aorta, bovine vena cava, and baboon cephalic vein but not in human umbilical or saphenous vein EC. External Na/sup +/ or Cl/sup -/-stimulated, ouabain-insensitive /sup 86/Rb influx is equal to furosemide or bumetanide-sensitive /sup 86/Rb influx. Ouabain-insensitive /sup 22/Na influx is also partially inhibited by these drugs and stimulated by increasing external K/sup +/ or Cl/sup -/. Net Na/sup +/ extrusion occurs via the Na/sup +/-K/sup +/-Cl/sup -/ cotransporter in the absence of external K/sup +/, whereas net Na/sup +/ influx occurs at higher external K/sup +/. Maximal concentrations (100 nM) of bradykinin and vasopressin increase the initial rate of bumetanide-sensitive /sup 86/Rb influx by approx.60 and 70%. Addition of either ethyleneglycol-bis(..beta..-aminotethylether)-N,N'-tetraacetic acid or LaCl/sub 3/ (to block calcium influx) prevents bradykinin-stimulated /sup 86/Rb influx. When intracellular calcium is elevated using ionomycin (100 nM), a Ca/sup 2 +/ionophore, bumetanide-sensitive /sup 86/Rb influx increases approx.twofold. In contrast, isoproterenol (100 ..mu..M) and forskolin (50 /sup +/M), adenylate cyclase stimulators, decrease furosemide-sensitive /sup 86/Rb influx. Thus in certain types of cultured EC, a Na/sup +/-K/sup +/-Cl/sup -/ cotransporter mediates a fraction of K/sup +/ influx quantitatively as important as the Na/sup +/-K/sup +/ pump (ouabain-sensitive /sup 86/Rb influx) and appears to be modulated by Ca/sup 2 +/ and cyclic nucleotides.

  5. Neuregulin-1-mediated ErbB2-ErbB3 signalling protects human trophoblasts against apoptosis to preserve differentiation.

    Science.gov (United States)

    Fock, Valerie; Plessl, Kerstin; Draxler, Peter; Otti, Gerlinde Regina; Fiala, Christian; Knöfler, Martin; Pollheimer, Jürgen

    2015-12-01

    During placentation, foetal trophoblasts invade deeply into maternal tissue to establish a foeto-maternal circulation. We have previously shown that extravillous trophoblast (EVT) lineage cells express ErbB2 and ErbB3, of which the potential as an oncogenic unit is well established. However, a physiological function of this receptor combination in humans remains a puzzling question. Here, we demonstrate neuregulin 1 (NRG1) expression and secretion by human decidual stromal cells. Stimulation of human primary trophoblasts with exogenous NRG1 induced phosphorylation of ErbB2, ErbB3 and related downstream effectors. Co-immunoprecipitation experiments confirmed the formation of ErbB2-ErbB3 dimers upon ligand engagement. Along this line, receptor knockdown and ErbB3 neutralization strongly diminished NRG1-dependent activation of the signalling complex. Functional studies revealed that NRG1 promotes EVT formation in placental explant cultures. Although, in the presence of NRG1, basal and camptothecin-induced trophoblast apoptosis was significantly repressed, this effect was abolished upon ErbB3 inhibition. Notably, camptothecin provoked a strong reduction of trophoblast cell column size, whereas NRG1-treated explants were refractory to the compound. Taken together, our findings newly identify a physiological function of the NRG1-ErbB2-ErbB3 axis in trophoblast survival during human placental development. PMID:26490994

  6. ErbB2, but not ErbB1, reinitiates proliferation and induces luminal repopulation in epithelial acini

    Energy Technology Data Exchange (ETDEWEB)

    Muthuswamy, Senthil K; Li, Dongmei; Lelievre, Sophie; Bissell, Mina J; Brugge, Joan S

    2001-08-08

    Both ErbB1 and ErbB2 are overexpressed or amplified in breast tumors. To examine the effects of activating ErbB receptors in a context that mimics polarized epithelial cells in vivo, we activated ErbB1 and ErbB2 homodimers in preformed, growth-arrested mammary acini cultured in three-dimensional basement membrane gels. Activation of ErbB2, but not that of ErbB1, led to a reinitiation of cell proliferation and altered the properties of mammary acinar structures. These altered structures share several properties with early-stage tumors, including a loss of proliferative suppression, an absence of lumen, retention of the basement membrane and a lack of invasive properties. ErbB2 activation also disrupted tight junctions and the cell polarity of polarized epithelia, whereas ErbB1 activation did not have any effect. Our results indicate that ErbB receptors differ in their ability to induce early stages of mammary carcinogenesis in vitro and this three-dimensional model system can reveal biological activities of oncogenes that cannot be examined in vitro in standard transformation assays.

  7. Il B2B e il paradigma dei costi di transazione (B2B and the Transaction Costs Paradigm

    Directory of Open Access Journals (Sweden)

    Pierluigi Sabbatini

    2012-04-01

    Full Text Available Business to Business (B2B Internet commerce causes a significant contraction of transaction costs. According to the Coase paradigm, we would thus expect a deverticalization of the industry and broader scope for anonymous market mechanisms. In reality, such expectations are not fully borne out by the facts. When the industrial structure is concentrated the B2Bgenerally loses its independence, and is owned by the firms which most contribute to its development, e.g. the ones able to bring the liquidity to it. The B2B governance mechanism established by these firms gives hierarchical mechanisms a role which they do not usually play in extensive, anonymous markets.         JEL Codes: D23, L86Keywords: Cost, Transaction Costs, Transactions

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    modulus 180-200GPa), while TiB2 may be classified as superhard (bulk modulus about 260GPa). We report here first experimental and theoretical determinations of the bulk modulus for HoB4 (195(5) and 198.2GPa, respectively), and first experimental values of the bulk modulus for ScB2 (196(2)GPa) and YB4 (185......(4)GPa). No pressure-induced phase transformations are observed in any of the above borides up to about 20GPa. A continuous temperature-driven orthorhombic distortion is observed for HoB4 below 285K. Values of the thermal expansion coefficient are reported for ScB2 and HoB4 at 293, 200 and 100K...

  9. Preparation and characterisation of Os doped MgB2

    International Nuclear Information System (INIS)

    Highlights: • Polycrystalline osmium doped MgB2 samples were prepared by solid state route. • Up to 1 at.% Mg can be replaced by Os in the MgB2 lattice. • Tc decreases at a rate of 2.1 K/at.% Os upon doping. - Abstract: Polycrystalline samples with Mg1−xOsxB2.04 nominal stoichiometry were made by reacting elemental powders at 800 °C under argon atmosphere. Based on XRD diffraction patterns, EDS analysis and magnetisation measurements, it is found that Os can replace up to about 1 at.% Mg in the MgB2 lattice. Beyond this doping level, unreacted Os and Mg-rich Mg–Os impurity phases are formed. The a-axis parameter contracts upon doping while the superconducting transition temperature decreases at a rate of 2.1 K/at.% Os substitution. At 10 K, Os doping induces an improvement of the normalised critical current density under applied magnetic fields in excess of 0.5 T, indicating a modest enhancement of flux pinning in this range

  10. Structural, electronic and magnetic properties of MnB2

    Indian Academy of Sciences (India)

    R Masrour; E K Hlil; M Hamedoun; A Benyoussef; O Mounkachi; H El Moussaoui

    2015-08-01

    The self-consistent ab-initio calculations, based on density functional theory approach and using the full potential linear augmented plane wave method, are performed to investigate both electronic and magnetic properties of the MnB2 compounds. Polarized spin and spin–orbit coupling are included in calculations within the framework of the ferromagnetic state between two adjacent Mn atoms. Magnetic moment considered to lie along the (001) axes are computed. The antiferromagnetic and ferromagnetic energies of MnB2 systems are obtained. Obtained data from ab-initio calculations are used as input for the high-temperature series expansions (HTSEs) calculations to compute other magnetic parameters. The exchange interactions between the magnetic atoms Mn–Mn in MnB2 are established by using the mean field theory. The HTSEs of the magnetic susceptibility with the magnetic moments in MnB2 (Mn) through Ising model is given. The critical temperature C (K) is obtained by HTSEs applied to the magnetic susceptibility series combined with the Padé approximant method. The critical exponent associated with the magnetic susceptibility is deduced as well.

  11. Electronic and bonding properties of TiB2

    International Nuclear Information System (INIS)

    The structural and electronic properties of TiB2 have been calculated using the first-principles total-energy pseudopotential method based on density functional theory. It is shown that the calculated lattice constants and heat of formation of TiB2 are in good agreement with the experimental results. By analyzing the band structure, density of states and Mulliken population, it is found that the bonding nature in TiB2 is a combination of ionic, covalent and metallic. The 2s-2p interaction exists in the close-packed layer of boron atoms. The hybridization of Ti-3d and B-2p from different layers is the main reason for the creation of pseudogap and results in the strong interlayer covalent bonding. In the same time, the charge transfer from titanium to boron is as significant as 1.16 electrons in the present case. The d-d resonance and free-electron 3d states of titanium atoms contribute to the covalent and metallic bonding in the layer of titanium atoms

  12. Investigation of TaC–TaB2 ceramic composites

    Indian Academy of Sciences (India)

    Behzad Mehdikhani; Gholam Hossein Borhani; Saeed Reza Bakhshi; Hamid Reza Baharvandi

    2016-02-01

    The TaC–TaB2 composition was sintered by spark plasma (SPS) at 1900–2100°C and applied pressure of 30 MPa. TaC and 2–3 wt% B4C were used as starting powders. Densification process, phase evolution, microstructure and the mechanical properties of the composites were investigated. The results indicated that the TaC–TaB2 composition could be SPS to 97% of theoretical density in 10 min at 2100°C. Addition of B4C leads to an increase in the density sample from 76 to 97%. B4C nano-powder resists grain growth even at high temperature 2100°C. The formation of TaB2/carbon at TaC grain boundaries helps in pinning the grain boundary and inhibiting grain growth. The phase formation was associated with carbon and boron diffusion from the starting particles B4C to form TaB2 phases. TaC grain sizes decreased with increase in B4C concentration. Samples with 2.0 wt% B4C composition had highest flexure strength up to 520 MPa. The effect of B4C addition on hardness measured by microhardness has been studied. Hardness of samples containing 3.0 wt% B4C was 16.99 GPa.

  13. Marketing-sales interface configurations in B2B firms

    NARCIS (Netherlands)

    Biemans, Wim G.; Brencic, Maja Makovec; Malshe, Avinash; Makovec Brenciv, M.

    2010-01-01

    As the body of knowledge on marketing-sales interface expands, there is a greater need to investigate the specific aspects of marketing-sales configurations in B2B firms. Using a qualitative methodology and interview data collected from over 100 sales and marketing professionals from the US, The Net

  14. 26 CFR 48.4161(b)-2 - Meaning of terms.

    Science.gov (United States)

    2010-04-01

    ...)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS EXCISE TAXES MANUFACTURERS AND RETAILERS EXCISE TAXES Sporting Goods § 48.4161(b)-2 Meaning of terms. (a) For purposes of the tax imposed by section 4161(b), and unless otherwise expressly indicated: (1)...

  15. Supporting B2B Business Documents in XML Web Services

    Institute of Scientific and Technical Information of China (English)

    KIM Hyoungdo

    2004-01-01

    While XML web services become recognized as a solution to business-to-business transactions, there are many problems that should be solved. For example, it is not easy to manipulate business documents of existing standards such as RosettaNet and UN/EDIFACT EDI, traditionally regarded as an important resource for managing B2B relationships. As a starting point for the complete implementation of B2B web services, this paper deals with how to support B2B business documents in XML web services. In the first phase, basic requirements for driving XML web services by business documents are introduced. As a solution, this paper presents how to express B2B business documents in WSDL, a core standard for XML web services. This kind of approach facilitates the reuse of existing business documents and enhances interoperability between implemented web services. Furthermore, it suggests how to link with other conceptual modeling frameworks such as ebXML/UMM, built on a rich heritage of electronic business experience.

  16. In silico structure-function analysis of pathological variation in the HSD11B2 gene sequence

    OpenAIRE

    Manning, Jonathan R.; Bailey, Matthew A; Soares, Dinesh C.; Dunbar, Donald R.; Mullins, John J.

    2010-01-01

    11β-Hydroxysteroid dehydrogenase type 2 (11βHSD2) is a short-chain dehydrogenase/reductase (SDR) responsible for inactivating cortisol and preventing its binding to the mineralocorticoid receptor (MR). Nonfunctional mutations in HSD11B2, the gene encoding 11βHSD2, cause the hypertensive syndrome of apparent mineralocorticoid excess (AME). Like other such Mendelian disorders, AME is rare but has nevertheless helped to illuminate principles fundamental to the regulation of blood pressure. Furth...

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

    International Nuclear Information System (INIS)

    We studied the directional crystallization of different compositions in B4C-NbB2 and B4C-MoB2 systems. The eutectic compositions for both systems are evaluated. It is shown that in the first system the rod-like eutectic structure is formed, in second, the 'Chinese hieroglyphics'. In both cases high hardness and high microplasticity are observed, which are much more than for individual component phases. These compositions may be considered as a new kind of self-strengthening composite materials

  18. Interaction between bradykinin potentiating nonapeptide (BPP9a) and β-cyclodextrin: A structural and thermodynamic study

    International Nuclear Information System (INIS)

    Herein, we demonstrate the physical and chemical characterizations of the supramolecular complex formed between β-cyclodextrin (βCD) and bradykinin potentiating nonapeptide (BPP9a), an endogenous toxin found in Bothrops jararaca. Circular dichroism results indicate a conformational change in the BPP9a secondary structure upon its complexation with βCD. Nuclear magnetic resonance results, mainly from NOESY experiments, and theoretical calculations showed a favorable interaction between the tryptophan residue of BPP9a and the βCD cavity. Thermodynamic inclusion parameters were investigated by isothermal titration calorimetry, demonstrating that βCD/BPP9a complex formation is an exothermic process that results in a reduction in entropy. Additionally, in vitro degradation study of BPP9a against trypsin (37 °C, pH 7.2) showed higher stability of peptide in presence of βCD. This βCD/BPP9a complex, which presents new chemical properties arising from the peptide inclusion process, may be useful as an antihypertensive drug in oral pharmaceutical formulations. Highlights: ► Cd and NMR showed evidences for the existence of more than one structure in solution. ► Complexation with βCD reduces the conformational rigidity of the peptide. ► βCD cavity recognize Trp and/or Pro segments of BPP9a. ► Interactions involving disaggregation of BPP9a assemblies and binding with βCD.

  19. Interaction between bradykinin potentiating nonapeptide (BPP9a) and {beta}-cyclodextrin: A structural and thermodynamic study

    Energy Technology Data Exchange (ETDEWEB)

    Lula, Ivana; De Sousa, Frederico B. [Departamento de Quimica, Instituto de Ciencias Exatas, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, 31270-901, Belo Horizonte, MG (Brazil); Denadai, Angelo M.L. [Centro Federal de Educacao Tecnologica de Minas Gerais, CEFET-MG, Campus VII, 35.183-006, Timoteo, MG (Brazil); Ferreira de Lima, Guilherme; Duarte, Helio Anderson [Departamento de Quimica, Instituto de Ciencias Exatas, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, 31270-901, Belo Horizonte, MG (Brazil); Mares Guia, Thiago R. dos [Departamento de Bioquimica e Imunologia, ICB, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG (Brazil); Faljoni-Alario, Adelaide [Departamento de Bioquimica, Instituto de Quimica, Universidade de Sao Paulo, 05508-900, Sao Paulo, SP (Brazil); Santoro, Marcelo M. [Departamento de Bioquimica e Imunologia, ICB, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG (Brazil); Camargo, Antonio C.M. de [Center for Applied Toxinology CAT-CEPID, Laboratorio Especial de Toxicologia Aplicada, Instituto Butantan, 05503-900, Sao Paulo, SP (Brazil); Santos, Robson A.S. dos [Departamento de Fisiologia e Biofisica, ICB, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG (Brazil); and others

    2012-02-01

    Herein, we demonstrate the physical and chemical characterizations of the supramolecular complex formed between {beta}-cyclodextrin ({beta}CD) and bradykinin potentiating nonapeptide (BPP9a), an endogenous toxin found in Bothrops jararaca. Circular dichroism results indicate a conformational change in the BPP9a secondary structure upon its complexation with {beta}CD. Nuclear magnetic resonance results, mainly from NOESY experiments, and theoretical calculations showed a favorable interaction between the tryptophan residue of BPP9a and the {beta}CD cavity. Thermodynamic inclusion parameters were investigated by isothermal titration calorimetry, demonstrating that {beta}CD/BPP9a complex formation is an exothermic process that results in a reduction in entropy. Additionally, in vitro degradation study of BPP9a against trypsin (37 Degree-Sign C, pH 7.2) showed higher stability of peptide in presence of {beta}CD. This {beta}CD/BPP9a complex, which presents new chemical properties arising from the peptide inclusion process, may be useful as an antihypertensive drug in oral pharmaceutical formulations. Highlights: Black-Right-Pointing-Pointer Cd and NMR showed evidences for the existence of more than one structure in solution. Black-Right-Pointing-Pointer Complexation with {beta}CD reduces the conformational rigidity of the peptide. Black-Right-Pointing-Pointer {beta}CD cavity recognize Trp and/or Pro segments of BPP9a. Black-Right-Pointing-Pointer Interactions involving disaggregation of BPP9a assemblies and binding with {beta}CD.

  20. Conformations of Prolyl-Peptide Bonds in the Bradykinin 1-5 Fragment in Solution and in the Gas Phase.

    Science.gov (United States)

    Voronina, Liudmila; Masson, Antoine; Kamrath, Michael; Schubert, Franziska; Clemmer, David; Baldauf, Carsten; Rizzo, Thomas

    2016-07-27

    The dynamic nature of intrinsically disordered peptides makes them a challenge to characterize by solution-phase techniques. In order to gain insight into the relation between the disordered state and the environment, we explore the conformational space of the N-terminal 1-5 fragment of bradykinin (BK[1-5](2+)) in the gas phase by combining drift tube ion mobility, cold-ion spectroscopy, and first-principles simulations. The ion-mobility distribution of BK[1-5](2+) consists of two well-separated peaks. We demonstrate that the conformations within the peak with larger cross-section are kinetically trapped, while the more compact peak contains low-energy structures. This is a result of cis-trans isomerization of the two prolyl-peptide bonds in BK[1-5](2+). Density-functional theory calculations reveal that the compact structures have two very different geometries with cis-trans and trans-cis backbone conformations. Using the experimental CCSs to guide the conformational search, we find that the kinetically trapped species have a trans-trans configuration. This is consistent with NMR measurements performed in a solution, which show that 82% of the molecules adopt a trans-trans configuration and behave as a random coil. PMID:27366919

  1. Microstructural and electrical characterization of MgB2 produced from boron oxide (B2O3)

    International Nuclear Information System (INIS)

    The discovery of superconducting MgBz (39 K) draws attention as a new material for appIications based on superconductivity. Many researchers successfulIy synthesized MgB2 using commercial Boron (B) and Magnesium (Mg). Due to the fact that Turkey is rich in amount of B203, in this studyelemental boron is synthesized from B203. Boron is obtained by acid leaching process af ter sintering B203 and Mg in Argon atmosphere at 800 degrees for Ih. EDX (Electron Dispersive X-ray Spectroscopy) results revealed that the obtained powder was Boron in 92% purity with Mg as a major impuriy. Superconducting MgB2 is produced from acquired Boron and Magnesium in Argon atmosphere at 9000C by a conventional solid state reaction. Phase identification and microstructural properties of MgB2 is determined by using XRD (X-ray Diffraction Spectroscopy), EDX and SEM (Scanning Electron Microscopy) techniques. Electrical properties of fabricated MgB2 is analyzed by resistivity measurements with closed-cycle. He cooled system between 20 and 300 K

  2. Structure and magnetism of MnMgB2O5 and Mn2B2O5

    International Nuclear Information System (INIS)

    We present an investigation of the magnetic properties of the pyroborates Mn2B2O5 and MnMgB2O5 using magnetization and electron-paramagnetic-resonance measurements. The pyroborates have in common with another well studied family of borates, the warwickites, substructures in the form of ribbons where the metals are located. The homometallic Mn2B2O5 system is shown to be a conventional three-dimensional antiferromagnet with Neel temperature TN≅24 K. Its magnetization isotherms present steps indicating spin-flop-like transitions involving distinct pairs of metal sites. The heterometallic compound MnMgB2O5 shows a susceptibility with a power-law temperature dependence χ(T)∝T-α, down to T=1.8 K and a magnetization with a power-law field dependence M(H)∝H(1-α) at low temperatures. This behavior is characteristic of a random singlet phase, in this case, in a system with spin S=5/2. We discuss our magnetic results on the pyroborates in connection with their structure and compare them with those obtained in the warwickites

  3. An ab initio molecular dynamics study on the structural and electronic properties of AlB2, TiB2 and (Alx,Ti(1−x))B2 in Al–Ti–B master alloys

    International Nuclear Information System (INIS)

    Highlights: • The dominant bonding of AlB2 and TiB2 are ionic and covalent, respectively. • The covalent bonding nature of AlB2 and TiB2 are strengthened with increasing temperature. • The different bonding natures between Al–B and Ti–B weaken the cohesion of (Alx Ti(1−x))B2. • The higher formation energy of (Alx Ti(1−x))B2 is a barrier for the transformation from AlB2 to TiB2. -- Abstract: The structural and electronic properties of AlB2, TiB2 and (Alx,Ti(1−x))B2 diborides in Al–Ti–B master alloys are investigated by ab initio molecular dynamics calculations at high temperature. It is found that the dominant bonding states of AlB2 and TiB2 at 1073 K are ionic and covalent, respectively. The larger linear thermal expansion coefficient of AlB2 than that of TiB2 results from their different bonding nature. The original ionic or covalent bonding states of Al or Ti with B atoms is reversed to be covalent or ionic to suit the whole bonding environment of the diborides when Al or Ti atoms acts as the solute atoms replacing Ti or Al atoms to form (Alx,Ti(1−x))B2 duplex diborides. The inter-layer cohesion in (Alx,Ti(1−x))B2 diborides is weakened owing to the weakened bonding and enhanced anti-bonding of Al–B and Ti–B bonds. The thermal stability of (Alx,Ti(1−x))B2 duplex diborides compared with AlB2 and TiB2 are elucidated from thermodynamic considerations. The higher formation energy of (Alx,Ti(1−x))B2 duplex diborides is a barrier for restricting the transformation from AlB2 to TiB2

  4. Strongly bound metastable states of B2 + 2

    Science.gov (United States)

    Bruna, Pablo J.; Wright, James S.

    1990-08-01

    The stabilities of about 25 electronic states of B2+2 have been investigated using a multireference CI (MRD-CI) method and an AO basis set composed of 6s4p2d contracted Gaussian species per atom, including semidiffuse functions relevant for an adequate description of charge transfer interactions. The ground state X1∑+g (σ2gσ2u) is repulsive, as expected by its electronic configuration with a zero bond order. In spite of this and the doubly-positive charge, many excited states are found to be metastable, four of them (11∏g, 11∏u, 13∑-g, and 11Δg ) having potential wells from 1.52 eV (11∏u) to 2.83 eV (13∑-g). Relative to the ground state configuration, the metastable states arise from the excitations σu→σg(3∑+u), σu→πu(3,1∏g), σ2u→σgπu(3,1∏u), and σ2u→π2u(3∑-g, 1Δg, 1∑+g); they are analogous to those states showing deep local minima in B2 and B+2. Differences in stabilities among quasibound states can be explained on the basis of the asymptotic ΔE's between repulsive channels B++B+ and appropriate higher-lying limits (states) B+B2+ of bonding character; another important factor governing stability is the actual bonding character of the electronic configurations assigned to each state. The vertical double-ionization potential B2B2+2(π2u→∞) between both ground states is 27.97 eV, the repulsive X1∑+g dication state being created with 8.37 eV excess energy relative to B++B+. Doubly-ionized states with a chance of being detected because of their long lifetimes against predissociation are those showing a strongly quasibound character, such as (with the vertical double ionization potential in eV given in parentheses): 11∏g(σuπu→∞; 30.29); 11∏u(σ2uπu→σg∞; 31.30); 13∑-g(σ2u→∞; 31.33), and 11Δg(σ2u→∞; 31.95).

  5. Investigation of pinning in MgB2 superconductors

    International Nuclear Information System (INIS)

    Full text: The pinning behaviour of bulk MgB2 superconductors is peculiar in many respects. Pinning seems to be stronger than in classical high TC materials and there seems to be no weak link problem in these compounds, giving hope to produce bulk samples and wires with current densities appropriate for technical applications. But, although many studies concerning the pinning behaviour in this compound appeared in recent years, the results are still contradictory. In the present work we present results of an investigation of the pinning behaviour by magnetic relaxation measurements of three MgB2 samples: a pure one, a sample with 8 at% Al substitution and a sample with 10 wt% of SiC admixture. A comparison of different analyses methods is given. (author)

  6. Compressibility of AlB2-type transition metal diborides

    International Nuclear Information System (INIS)

    The pressure behaviour of a series of transition metal borides has been studied both experimentally and by means of ab initio calculations. X-ray diffraction patterns measured up to ∼50 GPa for VB2 and ZrB2 show no obvious phase transition. Bulk moduli of 322 and 317 GPa, respectively, were obtained using a Murnaghan equation of state. Hartree-Fock LCCO (linear combination of crystal orbitals) calculations performed for TiB2 have allowed its compression behaviour to be studied. The bulk modulus obtained (292 GPa) and the proposed important contribution of the interlayer interaction to the elastic behaviour under high pressure are consistent with the experimental results for the other borides

  7. X-ray photoemission study of MgB2

    International Nuclear Information System (INIS)

    A c-axis oriented thin film and a high-density sintered pellet of MgB2 have been studied by x-ray photoemission spectroscopy, and compared to measurements from MgO and MgF2 single crystals. The as-grown surface has a layer which is Mg-rich and oxidized, which is effectively removed by a nonaqueous etchant. The subsurface region of the pellet is Mg deficient. This nonideal near-surface region may explain varied scanning tunneling spectroscopy results. The MgB2 core level and Auger signals are similar to measurements from metallic Mg and transition-metal diborides, and the measured valence band is consistent with the calculated density of states

  8. Compton profiles and electronic properties of TiB2

    International Nuclear Information System (INIS)

    In this paper, we report the experimental Compton profile (CP) of TiB2 using high energy 137Cs γ-rays Compton spectrometer. To interpret the experimental momentum density, we have calculated the CPs using Hartree-Fock (HF), density functional theory (DFT) and hybridization of DFT and HF within linear combination of atomic orbitals. The theoretical profile with generalized gradient approximation is found to be relatively in better agreement with the experimental profile. A sharp valley in density of states and hence the pseudogap near the Fermi energy is attributed to hybridization of Ti-3d and B-2p states and almost reverse trend of energy bands below and above the Fermi energy

  9. The presence of c-erbB-2 gene product-related protein in culture medium conditioned by breast cancer cell line SK-BR-3

    International Nuclear Information System (INIS)

    The Mr 185,000 glycoprotein encoded by human c-erbB-2/neu/HER2 gene, termed c-erbB-2 gene product, shows a close structural similarity with epidermal growth factor receptor and is now regarded to be a growth factor receptor for an as yet unidentified ligand. Abundant c-erbB-2 mRNA was demonstrated by Northern blot studies in the human breast cancer cell line SK-BR-3. Cellular radiolabeling experiments followed by immunoprecipitation with three different anti-c-erbB-2 gene product antibodies, recognizing extracellular domain, kinase domain, and carboxyl-terminal portion, respectively, demonstrated the production of a large amount of c-erbB-2 gene product which had the capacity to be phosphorylated. Immunization of mice with concentrated culture medium conditioned by SK-BR-3 cells always generated antibodies against c-erbB-2 gene product, demonstrating that this culture medium contained substance(s) immunologically indistinguishable from c-erbB-2 gene product. This observation was supported by the successful development of a monoclonal antibody against c-erbB-2 gene product, GFD-OA-p185-1, by immunizing mice with this culture medium. The biochemical nature of the substance(s) present in the culture medium was further characterized. When the culture medium conditioned by [35S]cysteine-labeled SK-BR-3 cells was immunoprecipitated by three different anti-c-erbB-2 gene product antibodies, only the antibody recognizing extracellular domain precipitated the [35S]-labeled protein with a molecular weight of 110,000, namely p110. The newly developed monoclonal antibody also immunoprecipitated this protein

  10. Performance and Applications of L1B2 Ultrasonic Motors

    OpenAIRE

    Gal Peled; Roman Yasinov; Nir Karasikov

    2016-01-01

    Piezoelectric ultrasonic motors offer important advantages for motion applications where high speed is coupled with high precision. The advances made in the recent decades in the field of ultrasonic motor based motion solutions allow the construction of complete motion platforms in the fields of semiconductors, aerospace and electro-optics. Among the various motor designs, the L1B2 motor type has been successful in industrial applications, offering high precision, effective control and operat...

  11. Social media usage: an investigation of B2B salespeople

    OpenAIRE

    Roberta J. Schultz; Charles H. Schwepker, Jr; David J. Good

    2012-01-01

    A great deal has been written recently in the practitioner press about the strategic importance and usage of social media. However, as practitioners only release limited information about the internal advantages such a tool provides, research in this emerging field remains extremely limited about its usage in the sales area. In this context, the purpose of this paper is to propose and empirically assess a model of social media usage among business-to-business (B2B) salespeople. A survey of 27...

  12. STRUCTURE ANALYSIS OF NEW SUPERCONDUCTOR MgB2

    Institute of Scientific and Technical Information of China (English)

    HE LUN-HUA; YAN QI-WEI; ZHANG PAN-LIN; HU GUI-QING

    2001-01-01

    The superconductivity of a sintered pellet of the newly discovered MgB2 superconductor has been studied with magnetic measurements and its crystal structure was analysed using the Rietveld method of powder X-ray patterns. It has hexagonal symmetry (S.G. P6/mmm) with unit cell lattice parameters a=0.308136(14)nm and c=0.351782(17)nm.

  13. EFFECTIVENESS OF BUSINESS PROCESS MANAGEMENT IN B2B MODEL

    OpenAIRE

    Monika £obaziewicz

    2013-01-01

    A dynamic progress in development of ICT technologies based on B2B, as well as their application in order to improve business processes carried out between enterprises and their business partners, have gained much importance during recent years. It was influenced by such factors as developing and tightening national and international cooperation, high competitiveness, time pressure and striving for improvement of customer and business partners service quality. While the reference books provid...

  14. Itinerant magnetism in CeRh3B2

    DEFF Research Database (Denmark)

    Eriksson, Olle; Johansson, Börje; Brooks, M. S. S.;

    1989-01-01

    Spin-polarized energy-band calculations, including spin-orbit coupling in the band Hamiltonian, have been performed on CeRh3B2. Good agreement is obtained between theory and experiment concerning the magnetic moment. It is also found that the magnetic moment varies strongly with volume and from t...... this a qualitative explanation for the anomalously high Curie temperature of the compound is proposed. Furthermore, the spin density is found to be highly nonspherical....

  15. Content Marketing vs. Traditional Advertising for B2B Companies

    OpenAIRE

    Anthony, Lorena

    2015-01-01

    This thesis follows a traditional research-based structure. The thesis focuses around content marketing and traditional advertising for B2B companies. The thesis was pro-duced for a company called INS and aims at showing that, in present times, content marketing is more valuable than traditional advertising. The first part of the thesis covers different views and theories on both content market-ing and traditional advertising, from definitions, types, roles and stages to planning and mea...

  16. CO and its Isotopomers Observation towards Sgr B2

    Indian Academy of Sciences (India)

    L. L. Sun; J. S. Zhang; D. R. Lu; J. J. Qiu

    2014-09-01

    We present our observations toward Sgr B2 region in = 1−0 lines of 12CO, 13CO, C18O and C17O using 13.7-m Delingha millimeter telescope with newly installed 9-beam SIS superconducting receiver. From the integrated line intensity, we derive the abundance ratio of C18O/C17O with a mean value of 3.11 ± 0.10, which is consistent with the previous results.

  17. Pressure dependent thermoelectric power of MgB$_2$ superconductor

    OpenAIRE

    Choi, E S; W. Kang; Kim, J.Y.; Park, Min-Seok; Jung, C. U.; Kim, Heon-Jung; Lee, Sung-Ik

    2001-01-01

    We have measured temperature dependence of thermoelectric power (TEP) on MgB$_2$ superconductor under hydrostatic pressure. The sign and temperature dependence of TEP shows metallic hole carriers are dominant with activation type contribution at higher temperature. TEP increases with pressure while $T_c$ decrease with ratio -0.136 K/kbar. The data are discussed in consideration of carriers from different bands and anisotropy of compressibility.

  18. Modernization of B-2 Data, Video, and Control Systems Infrastructure

    Science.gov (United States)

    Cmar, Mark D.; Maloney, Christian T.; Butala, Vishal D.

    2012-01-01

    The National Aeronautics and Space Administration (NASA) Glenn Research Center (GRC) Plum Brook Station (PBS) Spacecraft Propulsion Research Facility, commonly referred to as B-2, is NASA s third largest thermal-vacuum facility with propellant systems capability. B-2 has completed a modernization effort of its facility legacy data, video and control systems infrastructure to accommodate modern integrated testing and Information Technology (IT) Security requirements. Integrated systems tests have been conducted to demonstrate the new data, video and control systems functionality and capability. Discrete analog signal conditioners have been replaced by new programmable, signal processing hardware that is integrated with the data system. This integration supports automated calibration and verification of the analog subsystem. Modern measurement systems analysis (MSA) tools are being developed to help verify system health and measurement integrity. Legacy hard wired digital data systems have been replaced by distributed Fibre Channel (FC) network connected digitizers where high speed sampling rates have increased to 256,000 samples per second. Several analog video cameras have been replaced by digital image and storage systems. Hard-wired analog control systems have been replaced by Programmable Logic Controllers (PLC), fiber optic networks (FON) infrastructure and human machine interface (HMI) operator screens. New modern IT Security procedures and schemes have been employed to control data access and process control flows. Due to the nature of testing possible at B-2, flexibility and configurability of systems has been central to the architecture during modernization.

  19. ESR study on high Tc superconductor MgB2

    International Nuclear Information System (INIS)

    MgB2, a high-Tc superconductor, has been studied by Electron Spin Resonance (ESR) techniques at the temperature range of 6-300 K. Polycrystalline powders consisting of MgB2 and MgB4 phases were diluted and oriented in paraffin by applying an external magnetic field of 15 kG. A very narrow (2.5 G), strong, and isotropic signal that corresponded to almost free electron g-values was observed at all temperatures. Both the signal intensity and line width were observed to exhibit strong temperature dependence. The intensity of the ESR spectra, which corresponds to dc susceptibility, generally obeys the Curie law in this temperature range. However, some critical temperatures (approximately 215, 190, 150, and 39 K) were evident from both intensity and line width curves. While the ESR line is broadened, the signal intensity is drastically decreased just below T=39 K, corresponding to a transition temperature to a superconducting state. The origins of the minor changes both in the intensity and line width curves at other (higher) critical temperatures are not clear yet. In fact, the change at 215 K was observed to be meta-stable. These minor changes might be taken as signs for changes of local crystalline field symmetry around weakly localized conduction electrons or holes, which are the sources of the ESR signal in the MgB2 compound

  20. Fine-Filament MgB2 Superconductor Wire

    Science.gov (United States)

    Cantu, Sherrie

    2015-01-01

    Hyper Tech Research, Inc., has developed fine-filament magnesium diboride (MgB2) superconductor wire for motors and generators used in turboelectric aircraft propulsion systems. In Phase I of the project, Hyper Tech demonstrated that MgB2 multifilament wires (<10 micrometers) could reduce alternating current (AC) losses that occur due to hysteresis, eddy currents, and coupling losses. The company refined a manufacturing method that incorporates a magnesium-infiltration process and provides a tenfold enhancement in critical current density over wire made by a conventional method involving magnesium-boron powder mixtures. Hyper Tech also improved its wire-drawing capability to fabricate fine multifilament strands. In Phase II, the company developed, manufactured, and tested the wire for superconductor and engineering current density and AC losses. Hyper Tech also fabricated MgB2 rotor coil packs for a superconducting generator. The ultimate goal is to enable low-cost, round, lightweight, low-AC-loss superconductors for motor and generator stator coils operating at 25 K in next-generation turboelectric aircraft propulsion systems.

  1. Agent-based services for B2B electronic commerce

    Science.gov (United States)

    Fong, Elizabeth; Ivezic, Nenad; Rhodes, Tom; Peng, Yun

    2000-12-01

    The potential of agent-based systems has not been realized yet, in part, because of the lack of understanding of how the agent technology supports industrial needs and emerging standards. The area of business-to-business electronic commerce (b2b e-commerce) is one of the most rapidly developing sectors of industry with huge impact on manufacturing practices. In this paper, we investigate the current state of agent technology and the feasibility of applying agent-based computing to b2b e-commerce in the circuit board manufacturing sector. We identify critical tasks and opportunities in the b2b e-commerce area where agent-based services can best be deployed. We describe an implemented agent-based prototype system to facilitate the bidding process for printed circuit board manufacturing and assembly. These activities are taking place within the Internet Commerce for Manufacturing (ICM) project, the NIST- sponsored project working with industry to create an environment where small manufacturers of mechanical and electronic components may participate competitively in virtual enterprises that manufacture printed circuit assemblies.

  2. Fabrication and characterization of an MgB2 bolometer

    International Nuclear Information System (INIS)

    In this work, we present the experimental results obtained in the fabrication and characterization of a superconducting MgB2 bolometer. The device was made from an MgB2 meander-like structure suspended on a 500 nm thick SiN membrane. The MgB2 meander line was 50 μm wide and 7.6 mm long and it was defined by optical lithography and dry etching. The SiN membrane had an area of 1.3 mm x 1.3 mm and it was obtained by a silicon micromachining technique. The electrical and thermal properties of the device were measured at low temperature in a closed-cycle cryocooler. The resulting Tc of the meander was unchanged with respect to the unprocessed film and the transport properties, measured in voltage-biased mode, indicated a value for Jc of the order of 105 A cm-2 at 27 K. The logarithmic sensitivity of the bolometer turned out to be higher than 150. The study of the thermal properties of the bolometer on the membrane showed a thermal conductance of the order 10-5 W K-1 at a working temperature of 32 K. The bolometer, irradiated by a chopped laser beam, showed a cut-off frequency of 94 Hz. The maximum experimental responsivity was estimated to be 2.3 x 103 V W-1

  3. Kallikrein Promotes Inflammation in Human Dental Pulp Cells Via Protease-Activated Receptor-1.

    Science.gov (United States)

    Hayama, Tomomi; Kamio, Naoto; Okabe, Tatsu; Muromachi, Koichiro; Matsushima, Kiyoshi

    2016-07-01

    Plasma kallikrein (KLKB1), a serine protease, cleaves high-molecular weight kininogen to produce bradykinin, a potent vasodilator and pro-inflammatory peptide. In addition, KLKB1 activates plasminogen and other leukocyte and blood coagulation factors and processes pro-enkephalin, prorenin, and C3. KLKB1 has also been shown to cleave protease-activated receptors in vascular smooth muscle cells to regulate the expression of epidermal growth factor receptor. In this study, we investigated KLKB1-dependent inflammation and activation of protease-activated receptor-1 in human dental pulp cells. These cells responded to KLKB1 stimulation by increasing intracellular Ca(2+) , upregulating cyclooxygenase-2, and secreting prostaglandin E2 . Remarkably, SCH79797, an antagonist of protease-activated receptor-1, blocked these effects. Thus, these data indicate that KLKB1 induces inflammatory reactions in human dental tissues via protease-activated receptor 1. J. Cell. Biochem. 117: 1522-1528, 2016. © 2015 Wiley Periodicals, Inc. PMID:26566265

  4. On the luminescence of Ti4+ In Mg5SnB2O10 and Mg3ZrB2O8

    OpenAIRE

    Konijnendijk, W.L.; Blasse, G.

    1985-01-01

    The following new compounds are reported: Mg5TiB2O10 (ludwigite structure), Mg5SnB2O10 (orthopinakiolite structure) and Mg3ZrB2O8 (warwickite structure). The luminescences of the systems Mg5(Sn,Tl)B2O10 and Mg3(Zr,Ti)B2O8 were measured. The results are discussed in terms of delocalization in clusters of titanate octahedra. A general scheme for the luminescence of Ti4+-activated compositions is given. The composition Mg5SnB2O10: Ti is a very efficient luminescent material for titanium concentr...

  5. ErbB2 enhances mammary tumorigenesis, oncogene-independent recurrence and metastasis in a model of IGF-IR-mediated mammary tumorigenesis

    Directory of Open Access Journals (Sweden)

    Campbell Craig I

    2010-09-01

    Full Text Available Abstract Background The type I insulin-like growth factor receptor (IGF-IR and ErbB2 (Her-2 are receptor tyrosine kinases implicated in human breast cancer. Both proteins are currently the subject of targeted therapeutics that are used in the treatment of breast cancer or which are in clinical trials. The focus of this study was to utilize our inducible model of IGF-IR overexpression to explore the interaction of these two potent oncogenes. Results ErbB2 was overexpressed in our RM11A cell line, a murine tumor cell line that overexpresses human IGF-IR in an inducible manner. ErbB2 conferred an accelerated tumor onset and increased tumor incidence after injection of RM11A cells into the mammary glands of syngeneic wild type mice. This was associated with increased proliferation immediately after tumor cell colonization of the mammary gland; however, this effect was lost after tumor establishment. ErbB2 overexpression also impaired the regression of established RM11A tumors following IGF-IR downregulation and enhanced their metastatic potential. Conclusion This study has revealed that even in the presence of vast IGF-IR overexpression, a modest increase in ErbB2 can augment tumor establishment in vivo, mediate resistance to IGF-IR downregulation and facilitate metastasis. This supports the growing evidence suggesting a possible advantage of using IGF-IR and ErbB2-directed therapies concurrently in the treatment of breast cancer.

  6. Electric-quadrupole interaction at 181Hf/181Ta in Hf doped MgB2 and HfB2: a perturbed angular correlation study

    International Nuclear Information System (INIS)

    Hyperfine interaction of the 181Hf/181Ta is studied in HfB2 and Hf doped MgB2 by perturbed angular correlation spectroscopy. Nuclear quadrupole constants and attenuation factors were extracted from the data. Quadrupole coupling constant shows that Hf goes to three inequivalent sites in MgB2. There is sign of HfB2 formation at high temperature. (author)

  7. Effect of treatment with vitamin D3 on the responses of the duodenum of spontaneously hypertensive rats to bradykinin and to potassium.

    OpenAIRE

    Feres, T.; Vianna, L. M.; Paiva, A. C.; Paiva, T B

    1992-01-01

    1. The diet of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) and Wistar (NWR) rats was supplemented with either 2% calcium lactate in the drinking water or 12.5 micrograms vitamin D3 100 g-1 body weight daily by gavage, for 14 days. 2. The blood pressure of the SHR treated with either calcium or vitamin D decreased to the same levels as that of WKY and NWR. 3. The response to bradykinin of the SHR isolated duodenum, which is predominantly contractile, upon treatmen...

  8. Icatibant er en ny behandlingsmulighed ved livstruende angiotensinkonverterende enzym-inhibitor-udløst angioødem

    DEFF Research Database (Denmark)

    Fast, Søren; Henningsen, Emil; Bygum, Anette

    2011-01-01

    A 78 year-old woman with life-threatening angiotensin-converting enzyme inhibitor (ACE-i) induced angioedema was unresponsive to conventional treatment with corticosteroids, antihistamines and epinephrine. She was successfully treated with icatibant licensed for treatment of hereditary angioedema...... knowing that both conditions involve bradykinin induced activation of bradykinin B2 receptors. Randomised, controlled trials are warranted to document the efficacy of icatibant in ACE-i angioedema....

  9. B2B Integration in Global Supply Chains

    DEFF Research Database (Denmark)

    Schubert, Petra; Legner, Christine

    2011-01-01

    we identify five integration scenarios. In the subsequent confirmatory phase of the research we analyse 112 real-world company cases to validate these five integration scenarios. Our research advances and deepens existing studies by developing a B2B reference model, which reflects the current state...... of practice and is independent of specific implementation technologies. In the next stage of the research the emerging reference model will be extended to create an assessment model for analysing the maturity level of a given company in a specific supply chain....

  10. Microwave absorption studies of MgB2 superconductor

    Indian Academy of Sciences (India)

    M K Bhide; R M Kadam; M D Sastry; Ajay Singh; Shashwati Sen; Manmeet Kaur; D K Aswal; S K Gupta; V C Sahni

    2002-05-01

    Microwave absorption studies have been carried out on MgB2 superconductor using a standard X-band EPR spectrometer. The modulated low-field microwave absorption signals recorded for polycrystalline (grain size ∼ 10m) samples suggested the absence of weak-link character. The field dependent direct microwave absorption has been found to obey a $\\sqrt{H}$ dependence with two different slopes, which indicated a transition from strongly pinned lattice to flux flow regime.

  11. Permanent magnet with MgB2 bulk superconductor

    Science.gov (United States)

    Yamamoto, Akiyasu; Ishihara, Atsushi; Tomita, Masaru; Kishio, Kohji

    2014-07-01

    Superconductors with persistent zero-resistance currents serve as permanent magnets for high-field applications requiring a strong and stable magnetic field, such as magnetic resonance imaging. The recent global helium shortage has quickened research into high-temperature superconductors (HTSs)—materials that can be used without conventional liquid-helium cooling to 4.2 K. Herein, we demonstrate that 40-K-class metallic HTS magnesium diboride (MgB2) makes an excellent permanent bulk magnet, maintaining 3 T at 20 K for 1 week with an extremely high stability (Tesla-class permanent-magnet applications.

  12. Current noise in MgB2 superconducting thin films

    International Nuclear Information System (INIS)

    In this paper we present some experimental results concerning the current noise produced during the resistive transition in MgB2 thin films. Preliminary investigations evidenced the presence of electrical noise whose power spectrum has a region of the 1/fn type with n ∼ 3. We suggest that the noise may originate from abrupt rearrangement of the current distribution inside the specimen during the percolative process of a diphasic system. Experimental measurements of the spectral components of the current noise taken during the resistive transition will be given and discussed

  13. On Heavy Carbon Doping of MgB$_2$

    OpenAIRE

    Kasinathan, Deepa; Lee, K. -W.; PICKETT, W.E.

    2004-01-01

    Heavy carbon doping of MgB$_2$ is studied by first principles electronic structure studies of two types, an ordered supercell (Mg(B$_{1-x}$C$_{x}$)$_{2}$,x=0.0833) and also the coherent potential approximation method that incorporates effects of B-C disorder. For the ordered model, the twofold degenerate $\\sigma$-bands that are the basis of the high temperature superconductivity are split by 60 meV (i.e.7 meV/%C) and the $\\sigma$ Fermi cylinders contain 0.070 holes/cell, compared to 0.11 for ...

  14. INTERNET-MARKKINOINTI B2B-LIIKETOIMINNASSA

    OpenAIRE

    Iiskola, Jani

    2010-01-01

    Opinnäyteyö toimeksiantajana toimi Artepro Oy. Työn tarkoituksena oli tutkita Internet-markkinoinnin osa-alueita erityisesti business-to-business liiketoimintaa ajatellen. Työn tavoittee-na oli laatia toimeksiantajayritykselle markkinointiohjeistus ja esittää hyviä käytänteitä verkossa markkinoimiseen. Työssä tutkittiin myös miten markkinointi B2B-liiketoiminnassa eroaa perinteisestä kuluttajamark-kinoinnista, sekä miten Internetin yhteisöllisyyden lisääntyminen on vaikuttanut perinteisii...

  15. B2B-verkkokaupan suunnittelu : Case Laihian Levypala Oy

    OpenAIRE

    Kotilainen, Sanna-Mari

    2014-01-01

    Tämän opinnäytetyön tarkoituksena oli toteuttaa B2B-verkkokaupan suunnitelma metallialan perheyritys Laihian Levypala Oy:lle. Idea verkkokaupasta lähti Nettikone.com-ilmoituspalvelun kautta saadusta myynnistä ja totesimme yrittäjän kanssa, että verkkokaupan perustaminen voisi olla sopiva opinnäyteprojekti. Projektin alkuvaiheessa toteutettiin kysely lähialueiden maanrakennus-, maatalous- ja metallialan pk-yrityksille. Kyselyn aiheita olivat halukkuus perustaa oma verkkokauppa, yleinen verk...

  16. B2B-verkkokaupan markkinointiviestintäsuunnitelma

    OpenAIRE

    Luoma, Hanna

    2015-01-01

    Opinnäytetyön aiheena oli luoda markkinointiviestintäsuunnitelma Yritys Oy:n kehitteillä olevalle verkkokaupalle. Työn tavoitteena oli markkinointiviestintäsuunnitelman avulla selvittää miten Yritys Oy:n B2B-verkkokauppa saadaan osaksi myyntitoimia ja miten se mahdollisimman tehokkaasti tuodaan asiakkaiden tietoisuuteen. Yritys Oy on vuonna 2003 perustettu perheyritys, jonka toiminta on kiinnitystekniikan tukkumyynti alan ammattilaisille. Yritys Oy:llä on useampi toimipiste ympäri Suomea...

  17. Neon ion Irradiation studies on MgB2 Superconductor

    OpenAIRE

    Talapatra, A.; Bandyopadhyay, S K; Sen, Pintu; P. Barat

    2004-01-01

    160 MeV Neon ion irradiation has been carried out on MgB2 polycrystalline pellets at various doses. There has not been any significant change in Tc except at the highest dose of 1x10^15 ions/cm^2. Increase in resistivity has been noticed. Resistivity data has been fitted with Bloch-Gruneisen function and the values of Debye temperature, residual resistivity and temperature coefficient of resistivity have been extracted for irradiated as well as unirradiated samples. The increase in the resist...

  18. Strategic Insights from Mystery Shopping in B2B Relationships

    DEFF Research Database (Denmark)

    Mattsson, Jan

    2012-01-01

    This paper describes how mystery shopping can be used to gain valuable strategic input in B2B service relationships. We account for a longitudinal case study framed as a natural experiment (duration 18 months) in a Swedish group of consultancy companies offering a wide selection of industrial...... services to large Scandinavian corporations. We account for and analyse the process of building a mystery shopping procedure to get strategic insights from engineers delivering temporary consultancy services to these clients. After a successful trial period with three mystery shoppers the experiment (a...

  19. MgB2 superconducting joints for persistent current operation

    Science.gov (United States)

    Patel, Dipak; Hossain, Md Shahriar Al; See, Khay Wai; Xu, Xun; Barua, Shaon; Ma, Zongqing; Choi, Seyong; Tomsic, Mike; Kim, Jung Ho

    2015-06-01

    High-performance superconducting joints are essential for realizing persistent-mode magnets. Herein, we propose a concept and fabrication of such superconducting joints, which yielded reliable performance in the operating temperature range of 4.2-25 K. MgB2-MgB2 joints in magnets are known to result in deterioration of localized electrical, thermal, and mechanical properties. To overcome these problems, the ends of the two wires are inserted into a pellet press, which is then filled with a mixture of unreacted magnesium and boron powders, followed by heat treatment. The critical current capacity and joint resistance were precisely evaluated by the standard four-probe method in open-circuit and by field-decay measurements in a closed-loop, respectively. These joints demonstrated up to 66% of the current-carrying capacity of unjoined wire at 20 K, 2 T and joint resistance of 1.4 × 10-12 Ω at 4.2 K in self-field.

  20. Preparation of highly preferred orientation TiB2 coatings

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    This paper focuses on the preparation of titanium diboride (TiB2) coatings on the graphite substrate by continuous current plating (CCP) and pulse current plating (PIC) electrochemical techniques in fluoride electrolytes (LiF-NaF-KF)containing K2TiF6 and KBF4 as the electrochemically-active components at 700℃. Thick leveled and uniform coatings were obtained and were composed of relatively pure TiB2. The effect of the experimental parameters on the microstructure of the coatings was studied. The results showed the electrodeposition with PIC produced coatings with better quality, when compared with those obtained by CCP, under the conditions of the current density i = 0.6 A/cm2, frequency = 100 Hz, and ton/toff = 4/1. XRD analysis indicated that the preferred orientation of coatings is (110) plane, which is in accordance with the prediction of the two-dimensional crystal nuclei theory. The effect of a ratio of ton/toff and frequency on the crystal size, texture coefficient and microstress was also investigated.

  1. Carbon Doped MgB2 Thin Films using TMB

    Science.gov (United States)

    Wilke, R. H. T.; Li, Qi; Xi, X. X.; Lamborn, D. R.; Redwing, J.

    2007-03-01

    The most effective method to enhance the upper critical field in MgB2 is through carbon doping. In the case of thin films, ``alloying'' with carbon has resulted in enhanced Hc2 values estimated to be as high as 70 T for H parallel to ab and 40 T for H perpendicular ab [1]. ``Alloying'' refers to the in-situ Hybrid Physical-Chemical Vapor Deposition (HPCVD) of carbon containing MgB2 films using (C5H5)2Mg as the carbon source. While these films exhibit enhanced Hc2 values, there are amorphous boron- carbon phases in the grain boundaries that reduce the cross section area for superconducting current. We present here the results of our attempts to make more homogeneously carbon doped thin films using gaseuous trimethyl-boron (TMB) as the carbon source. Initial results indicate different behavior upon carbon doping using TMB from carbon-alloying. The microstructures and upper critical fields of the carbon doped films using TMB and carbon alloyed films will be compared. [1] V. Braccini et al., Phys. Rev. B 71 (2005) 012504. [2] A.V. Pogrebnyakov et al., Appl. Phys. Lett 85 (2004) 2017.

  2. USING UML SCENARIOS IN B2B SYSTEMS

    Directory of Open Access Journals (Sweden)

    A. Jakimi

    2010-05-01

    Full Text Available Scenarios has become a popular technique for requirements elicitation and specification building. Since scenarios capture only partial descriptions of the system behavior, an approach for scenario composition and/or integration is needed to produce more complete specifications. The Unified Modeling Language (UML, which has become a standard notation for object-oriented modeling, provides a suitable framework for scenario acquisition using Use Case diagrams and Sequence or Collaboration diagrams. In this paper, we suggest an algorithmic and tool support for composing and integrating scenarios that are represented in form of sequence diagrams. We suggest four operators (;: sequential operator, ||: concurrent operator, ?: conditional operator and  * :iteration operator to compose a set of scenarios that describe a use case of a given system. In this paper, we suggest also to apply the scenario approach to B2B systems (Business to Business. We propose to develop B2B systems as a three activities process deriving formal specifications and code skeletons from UML scenarios. Activities of this proposed process are generally automatic and are supported by a set of developed algorithms and tools.

  3. Characterization of MgB2 Superconducting Hot Electron Bolometers

    Science.gov (United States)

    Cunnane, D.; Kawamura, J. H.; Wolak, M. A.; Acharya, N.; Tan, T.; Xi, X. X.; Karasik, B. S.

    2014-01-01

    Hot-Electron Bolometer (HEB) mixers have proven to be the best tool for high-resolution spectroscopy at the Terahertz frequencies. However, the current state of the art NbN mixers suffer from a small intermediate frequency (IF) bandwidth as well as a low operating temperature. MgB2 is a promising material for HEB mixer technology in view of its high critical temperature and fast thermal relaxation allowing for a large IF bandwidth. In this work, we have fabricated and characterized thin-film (approximately 15 nanometers) MgB2-based spiral antenna-coupled HEB mixers on SiC substrate. We achieved the IF bandwidth greater than 8 gigahertz at 25 degrees Kelvin and the device noise temperature less than 4000 degrees Kelvin at 9 degrees Kelvin using a 600 gigahertz source. Using temperature dependencies of the radiation power dissipated in the device we have identified the optical loss in the integrated microantenna responsible as a cause of the limited sensitivity of the current mixer devices. From the analysis of the current-voltage (IV) characteristics, we have derived the effective thermal conductance of the mixer device and estimated the required local oscillator power in an optimized device to be approximately 1 microwatts.

  4. The Microwave Sintering Technology and Its Application in the Synthesis of ZrB2

    Institute of Scientific and Technical Information of China (English)

    HE Zhiyong; LI Lin; PENG Xiaoyan

    2005-01-01

    The principles and features of microwave sintering, the application in refractories and synthesis methods of ZrB2 are reviewed. The synthesis results of ZrB2 by thermit deoxidate method show that production price of ZrB2 can be effectively lowered through microwave synthesis. It will expand the application of ZrB2 in refractories.

  5. Getting started with Oracle SOA B2B Integration a hands-on tutorial

    CERN Document Server

    Bhatia, Krishnaprem; Perlovsky, Alan

    2013-01-01

    This hands on tutorial gives you the best possible start you could hope for with Oracle B2B. Learn using real life scenarios and examples to give you a solid footing of B2B.This book is for B2B architects, consultants and developers who would like to design and develop B2B integrations using Oracle B2B. This book assumes no prior knowledge of Oracle B2B and explains all concepts from scratch using illustrations, real world examples and step-by-step instructions. The book covers enough depth and details to be useful for both beginner and advanced B2B users.

  6. Study of TaB2 and SiC additions on the properties of MgB2 superconducting bulks

    International Nuclear Information System (INIS)

    This paper describes the synthesis and modification of MgB2 bulk samples to produce better transport superconducting materials. The methodology uses a mixture of MgB2 with another diboride, TaB2, which has the same C32 hexagonal structure as MgB2. The simultaneous addition of TaB2 and SiC, which contributes carbon doping, is also investigated. As an important result, the critical current densities (Jc) were enhanced at low magnetic fields (0–2 T) when TaB2 alone was added. In addition, Jc was enhanced in the entire range of the measured applied magnetic fields when TaB2 was simultaneously added with SiC. Some explanations for this Jc enhancement are presented. (paper)

  7. Conservation of fiber structure and CD46 usage by subgroup B2 adenoviruses

    Energy Technology Data Exchange (ETDEWEB)

    Pache, Lars; Venkataraman, Sangita; Nemerow, Glen R.; Reddy, Vijay S. (Scripps)

    2009-08-28

    Most subgroup B2 adenoviruses use CD46 as their primary receptor. Recent structural and mutagenesis studies suggested that Ad11 and Ad35 likely engage this receptor in a very similar fashion. However, no comparative studies assessing the cell-associated CD46 binding efficiencies of different Ad fibers have been performed. We solved the crystal structure of Ad35 fiber knob and constructed a model of the fiber knob complexed with CD46. Comparison of our model with that of Ad11-CD46 showed that despite a larger CD46-interacting region in the IJ loop of Ad11, the buried surface area was very similar, suggesting that both fiber knobs might exhibit similar binding. In support of this, cell based competition studies demonstrated almost identical binding efficiencies of Ad11 and Ad35 fibers to cell surface CD46. These findings shed further light on CD46 association by Ad and could impact the selection of novel Ad types for gene transfer.

  8. Identification of bradykinin: related peptides from Phyllomedusa nordestina skin secretion using electrospray ionization tandem mass spectrometry after a single-step liquid chromatography

    Directory of Open Access Journals (Sweden)

    K Conceição

    2009-01-01

    Full Text Available Amphibian skin secretions are a source of potential new drugs with medical and biotechnological applications. Rich in peptides produced by holocrine-type serous glands in the integument, these secretions play different roles, either in the regulation of physiological skin functions or in the defense against predators or microorganisms. The aim of the present work was to identify novel peptides with bradykinin-like structure and/or activity present in the skin of Phyllomedusa nordestina. In order to achieve this goal, the crude skin secretion of this frog was pre-fractionated by solid phase extraction and separated by reversed-phase chromatography. The fractions were screened for low-molecular-mass peptides and sequenced by mass spectrometry. It was possible to identify three novel bradykinin-related peptides, namely: KPLWRL-NH2 (Pnor 3, RPLSWLPK (Pnor 5 and VPPKGVSM (Pnor 7 presenting vascular activities as assessed by intravital microscopy. Pnor 3 and Pnor 7 were able to induce vasodilation. On the other hand, Pnor 5 was a potent vasoconstrictor. These effects were reproduced by their synthetic analogues.

  9. 75 FR 23572 - Airworthiness Directives; Airbus Model A300 B2-1C, B2-203, B2K-3C, B4-103, B4-203, B4-2C...

    Science.gov (United States)

    2010-05-04

    ... CONTACT: Dan Rodina, Aerospace Engineer, International Branch, ANM-116, Transport Airplane Directorate... (75 FR 11428, March 11, 2010), for certain Airbus Model A300 B2-1C, B2-203, B2K-3C, B4-103, B4-203, B4... total flight \\1\\ '' has been corrected to read ''>17,500 total flight cycles \\1\\.'' (The word...

  10. Identification of New Methanol Lines toward Sagittarius B2

    Science.gov (United States)

    Pei, C. C.; Liu, Sheng-Yuan; Snyder, Lewis E.

    2000-02-01

    The first astronomical measurements of the Jk=182-181, 192-191, and 202-201 E transitions of methanol (CH3OH) are presented. A rotational temperature Trot=170(13) K was determined for the Sgr B2N-LMH core by combining the data from the Jk=132-131 and 172-171 E transitions. The total column density of CH3OH is NT(CH3OH)=4.2(6)x1017 cm-2, and the fractional abundance of CH3OH is X(CH3OH)~4x10-8. The H59α recombination line and a new unidentified line were detected.

  11. Vortex lattice transitions in YNi2B2C

    Indian Academy of Sciences (India)

    S J Levett; C D Dewhurst; D McK Paul

    2002-05-01

    We have performed extensive small-angle neutron scattering (SANS) diffraction studies of the vortex lattice in single crystal YNi2B2C for $B||c$. High-resolution SANS, combined with a field-oscillation vortex lattice preparation technique, allows us to separate Bragg scattered intensities from two orthogonal domains and accurately determine the unit cell angle, . The data suggest that upon increasing field there is a finite transition width where both low- and high-field distorted hexagonal vortex lattice phases, mutually rotated by 45°, coexist. The smooth variation of diffracted intensity from each phase through the transition corresponds to a redistribution of populations between the two types of domains.

  12. Specific heat of MgB2 after irradiation

    International Nuclear Information System (INIS)

    We studied the effect of disorder on the superconducting properties of polycrystalline MgB2 by specific-heat measurements. In the pristine state, these measurements give a bulk confirmation of the presence of two superconducting gaps with 2Δ0/kBTc=1.3 and 3.9 with nearly equal weights. The scattering introduced by irradiation suppresses Tc and tends to average the two gaps although less than predicted by theory. We also found that by a suitable irradiation process by fast neutrons, a substantial bulk increase of dHc2/dT at Tc can be obtained without sacrificing more than a few degrees in Tc. The upper critical field of the sample after irradiation exceeds 28 T at T→0

  13. Relationship Quality as Predictor of B2B Customer Loyalty

    Directory of Open Access Journals (Sweden)

    Shaimaa S. B. Ahmed Doma

    2013-02-01

    Full Text Available Relationship marketing has become extremely important recently due to the fierce competition in today's marketplace. Companies are required to build long-term profitable relationship with customers and to achieve customer loyalty. Also, switching behaviors frequently occur among most of targeted customers. Fewer studies, however, discuss the effects of relationship quality efforts on customer loyalty. Therefore, this study is aimed to investigate the impact of relationship quality on customer loyalty in B2B context in the Egyptian shipping services sector. Building on prior research, we propose relationship quality as a higher construct comprising trust, commitment and satisfaction. An analytical model is developed as a guideline to test the relationships between relationship quality dimensions and customer loyalty.

  14. Matchmaking Framework for B2B E-Marketplaces

    Directory of Open Access Journals (Sweden)

    Fekete ZOLTAN ALPAR

    2010-01-01

    Full Text Available In the recent years trading on the Internet become more popular. Online businesses gradually replace more and more from the conventional business. Much commercial information is exchanged on the internet, especially using the e-marketplaces. The demand and supply matching process becomes complex and difficult on last twenty years since the e-marketplaces play an important role in business management. Companies can achieve significant cost reduction by using e-marketplaces in their trade activities and by using matchmaking systems on finding the corresponding supply for their demand and vice versa. In the literature were proposed many approaches for matchmaking. In this paper we present a conceptual framework of matchmaking in B2B e-marketplaces environment.

  15. Widespread Occurrence of the Mycotoxin Fumonisin B-2 in Wine

    DEFF Research Database (Denmark)

    Mogensen, Jesper Mølgaard; Larsen, Thomas Ostenfeld; Nielsen, Kristian Fog

    2010-01-01

    Fumonisins are important mycotoxins because they are suspected to cause human and animal toxicoses by the consumption of contaminated corn-based food and feeds. However, with the discovery of fumonisin production in grapes by Aspergillus niger, wine may also be a fumonisin-containing commodity....... In the present study, we have developed a simple and quantitative cation-exchange-based purification method for the subsequent isotope dilution liquid chromatography tandem mass spectrometry (LC-MS/MS) determination of fumonisins in wine. A comparative study of seven different solid-phase extraction (SPE......) columns showed that polymeric mixed-mode reversed-phase (RP) cation-exchange columns were superior to classic silica-based cation and mixed-mode cation-exchange columns. A total of 77 wine samples from 13 countries were subsequently tested, and surprisingly, 18 (23%) were found to contain fumonisin B-2...

  16. Enhanced MgB2 Superconductivity Under High Pressure

    Institute of Scientific and Technical Information of China (English)

    刘振兴; 靳常青; 游江洋; 李绍春; 朱嘉林; 禹日成; 李风英; 苏少奎

    2002-01-01

    We report on in situ high-pressure studies up to 1.0 GPa on the MgB2 superconductor which was high-pressure synthesized. The as-prepared sample is of high quality in terms of sharp superconducting transition (Tc) at 39K from the magnetic measurements. The in situ high-pressure measurements were carried out using a Be-Cu piston-cylinder-type instrument with mixed oil as the pressure transmitting medium which warrants a quasihydrostatic pressure environment at low temperature. The superconducting transitions were measured using the electrical conductance method. It is found that Tc increases by more than 1 K with pressure in the low-pressure range, before the Tc value decreases with the further increase of the pressure.

  17. Sosiaalisen median strategia pienelle b2b-yritykselle

    OpenAIRE

    Surkko, Antti

    2012-01-01

    Sosiaalinen media on tänä päivänä tärkeä osa ihmisten elämää ja yritysten kannattaa siksi käyttää sitä hyödykseen markkinointitoimissaan. Aihe opinnäytetyöhön tuli toimeksiantajalta, joka on jo mukana sosiaalisen median palveluissa. Toimeksiantajayritys ei kuitenkaan tiedä, miten hyödyntää sosiaalisen median palveluiden täysi potentiaali markkinointikanavana. Opinnäytetyön tarkoituksena oli selvittää, mitä pienen b2b-yrityksen pitäisi ottaa huomioon sosiaalisen median markkinointitoimia aloi...

  18. Semantic ETL into i2b2 with Eureka!

    Science.gov (United States)

    Post, Andrew R; Krc, Tahsin; Rathod, Himanshu; Agravat, Sanjay; Mansour, Michel; Torian, William; Saltz, Joel H

    2013-01-01

    Clinical phenotyping is an emerging research information systems capability. Research uses of electronic health record (EHR) data may require the ability to identify clinical co-morbidities and complications. Such phenotypes may not be represented directly as discrete data elements, but rather as frequency, sequential and temporal patterns in billing and clinical data. These patterns' complexity suggests the need for a robust yet flexible extract, transform and load (ETL) process that can compute them. This capability should be accessible to investigators with limited ability to engage an IT department in data management. We have developed such a system, Eureka! Clinical Analytics. It extracts data from an Excel spreadsheet, computes a broad set of phenotypes of common interest, and loads both raw and computed data into an i2b2 project. A web-based user interface allows executing and monitoring ETL processes. Eureka! is deployed at our institution and is available for deployment in the cloud. PMID:24303265

  19. Structured Crowdsourcing: A B2B Innovation Roadmap

    DEFF Research Database (Denmark)

    Edgeman, Rick; Engell, Toke; Jensen, Nik Grewy;

    Crowdsourcing is an increasingly popular source of both ideas and funding. Crowdsourcing in a B2B context is less well understood and, as such, much of our discussion will highlight business-to-business crowdsourcing. More generally discussion will address crowdsourcing relative to innovation and...... technology development and customer relationship management. Examples will be used to derive a general roadmap, and to identify specific areas worthy of increased attention. The roadmap is developed as a six-stage approach that begins with task specification and concludes with management of inputs generated...... from crowd-sourcing efforts. The roadmap emphasizes on early stages in the overall innovation management activity that is related to development and specification of the task to be crowdsourced, the identification of the crowd, the creation of the environment to connect the crowdsourcer, the task and...

  20. Performance and Applications of L1B2 Ultrasonic Motors

    Directory of Open Access Journals (Sweden)

    Gal Peled

    2016-06-01

    Full Text Available Piezoelectric ultrasonic motors offer important advantages for motion applications where high speed is coupled with high precision. The advances made in the recent decades in the field of ultrasonic motor based motion solutions allow the construction of complete motion platforms in the fields of semiconductors, aerospace and electro-optics. Among the various motor designs, the L1B2 motor type has been successful in industrial applications, offering high precision, effective control and operational robustness. This paper reviews the design of high precision motion solutions based on L1B2 ultrasonic motors—from the basic motor structure to the complete motion solution architecture, including motor drive and control, material considerations and performance envelope. The performance is demonstrated, via constructed motion stages, to exhibit fast move and settle, a repeatability window of tens of nanometers, lifetime into the tens of millions of operational cycles, and compatibility with clean room and aerospace environments. Example stages and modules for semiconductor, aerospace, electro-optical and biomedical applications are presented. The described semiconductor and aerospace solutions are powered by Nanomotion HR type motors, driven by a sine wave up to 80 V/mm rms, having a driving frequency of 39.6 kHz, providing a maximum force up to 4 N per driving element (at 5 W power consumption per element and a maximum linear velocity above 300 mm/s. The described electro-optical modules are powered by small Nanomotion Edge motors driven by voltages up to 11 V AC, providing stall forces up to 0.35 N (power consumption up to 0.75 W and maximum linear velocity above 200 mm/s.

  1. Correlation of c-erbB-2, EGF and EGFR expression with postoperative survival of patients with advanced carcinoma of the stomach.

    Directory of Open Access Journals (Sweden)

    Katarzyna Guzinska-Ustymowicz

    2010-05-01

    Full Text Available The c-erbB-2 (HER-2/neu, EGF and EGFR (erbB-1 proteins, members of the epidermal growth factor receptor family, play a role in cell growth by binding to cell membrane receptors. The aim of the current study was to evaluate the expression of c-erbB-2, EGF and EGFR in advanced gastric carcinoma and to analyze its relationship with chosen anatomo-clinical parameters and prognosis. Standard avidin-biotin-peroxidase was used for c-erbB-2, EGF and EGFR immuno-histochemical staining (Novostain Super ABC Kit Universal; anti-human c-erbB-2 protein monoclonal antibody NCL-cerbB-2-316, anti-Epidermal Growth Factor monoclonal antibody (clone EGF-10 and EGFR goat polyclonal IgG (p-EGFR. A statistically significant correlation was found between c-erbB-2, EGF, EGRF expressions in the main mass of tumor and lymph node metastasis (p=0.000; p=0.000; p=0.00001, respectively. Also an association was observed between c-erbB-2 expression and Bormann's and Lauren's classifications (p=0.05; p=0.006, respectively. Similarly, the expression of EGFR in main mass of tumor was correlated with the depth of invasion (p=0.007 and histological differentiation (p=0.04. Moreover, the expression of c-erbB-2 in the main mass of tumor and lymph node metastasis was associated with the age of the patients (p=0.03; p=0.0002 respectively. Strong association was found between the expression of EGRF in lymph node metastasis and histological differentiation (p=0.04. Positive expression of c-erbB-2 in lymph node metastasis was correlated with lymph node involvement (p=0.04. Positive expression of c-erbB-2 in the main mass of tumor and in lymph node metastasis was strongly correlated with postoperative survival (p=0.00001; p=0.003 respectively. We also found a relationship between EGF expression in gastric tumor and survival time (p=0.003. No association was noted between the expression of EGFR in the main mass of tumor and in lymph node metastasis and between the expression of EGF in lymph

  2. The conserved nhaAR operon is drastically divergent between B2 and non-B2 Escherichia coli and is involved in extra-intestinal virulence.

    Directory of Open Access Journals (Sweden)

    Mathilde Lescat

    Full Text Available The Escherichia coli species is divided in phylogenetic groups that differ in their virulence and commensal distribution. Strains belonging to the B2 group are involved in extra-intestinal pathologies but also appear to be more prevalent as commensals among human occidental populations. To investigate the genetic specificities of B2 sub-group, we used 128 sequenced genomes and identified genes of the core genome that showed marked difference between B2 and non-B2 genomes. We focused on the gene and its surrounding region with the strongest divergence between B2 and non-B2, the antiporter gene nhaA. This gene is part of the nhaAR operon, which is in the core genome but flanked by mobile regions, and is involved in growth at high pH and high sodium concentrations. Consistently, we found that a panel of non-B2 strains grew faster than B2 at high pH and high sodium concentrations. However, we could not identify differences in expression of the nhaAR operon using fluorescence reporter plasmids. Furthermore, the operon deletion had no differential impact between B2 and non-B2 strains, and did not result in a fitness modification in a murine model of gut colonization. Nevertheless, sequence analysis and experiments in a murine model of septicemia revealed that recombination in nhaA among B2 strains was observed in strains with low virulence. Finally, nhaA and nhaAR operon deletions drastically decreased virulence in one B2 strain. This effect of nhaAR deletion appeared to be stronger than deletion of all pathogenicity islands. Thus, a population genetic approach allowed us to identify an operon in the core genome without strong effect in commensalism but with an important role in extra-intestinal virulence, a landmark of the B2 strains.

  3. ERBB2 in Cat Mammary Neoplasias Disclosed a Positive Correlation between RNA and Protein Low Expression Levels: A Model for erbB-2 Negative Human Breast Cancer

    OpenAIRE

    Santos, Sara; Batista, Claudia; Abreu, Rui M. V.; Bastos, Estela; Amorim, Irina; Gut, Ivo G.; Gartner, Fátima; Chaves, Raquel

    2013-01-01

    Human ERBB2 is a proto-oncogene that codes for the erbB-2 epithelial growth factor receptor. In human breast cancer (HBC), erbB-2 protein overexpression has been repeatedly correlated with poor prognosis. In more recent works, underexpression of this gene has been described in HBC. Moreover, it is also recognised that oncogenes that are commonly amplified or deleted encompass point mutations, and some of these are associated with HBC. In cat mammary lesions (CMLs), the overexpression of ERBB2...

  4. B2B E- Commercial Exchange Platform Based on RosettaNet%基于RosettaNet的B2B电子商务交换平台

    Institute of Scientific and Technical Information of China (English)

    钟山; 许炜

    2005-01-01

    B2B hub是简化Busines-to-Business(B2B)交换的一个中介体.通过B2B网关,管理不同贸易伙伴间消息交换的通信及安全问题,通过管理系统和数据转换引擎实现购买流程中,买卖双方的匹配.HUB架构中的核心部分是B2B集成服务器,它实现了RosettaNet以及其他B2B协议.因此,hub是一个在B2B集成服务器上的特殊应用.

  5. Experiences and Future Expectations towards Online Courses--An Empirical Study of the B2C-and B2B-Segments

    Science.gov (United States)

    Krämer, Andreas; Böhrs, Sandra

    2016-01-01

    This article explores the future potential for the development of online courses. The findings are based on an empirical study with 3 sample groups: (1) B2C segment in Germany, (2) B2C segment in the United States, and (3) B2B segment (international). In the first step the status quo of the use of e-learning in general and online courses in…

  6. Study on electronic commerce pattern of B2B in China%中国B2B电子商务模式研究

    Institute of Scientific and Technical Information of China (English)

    罗新方

    2008-01-01

    介绍了中国B2B的现状及五大发展趋势,指出了阻碍B2B企业发展的症结所在--模式选择不当,战略分析不清,盲目追从,缺乏创新.提出了几条适合中国B2B企业发展的创新途径.

  7. Study on Logistics Distribution Centers for B2C Online Shopping%B2C网购物流配送中心研究

    Institute of Scientific and Technical Information of China (English)

    侯凌燕; 尹军琪

    2011-01-01

    分析了我国B2C网购物流配送的现状,对其特点和难点作了分析,并提出了相应的B2C网购物流配送中心设计解决方案.%The paper analyzes the current status of the logistics and distribution operations for B2C online shopping in China, analyzes its characteristics and existing issues, and puts forth solutions for the design of logistics and distribution centers for B2C online shopping.

  8. Customer Behavior Analysis under B2C Environment%B2C环境下的客户行为分析

    Institute of Scientific and Technical Information of China (English)

    牛文博

    2012-01-01

    Taking the background of B2C e-commerce transactions, this paper starts from the objective of customer behavior analysis, proposes the process of customer behavior analysis based on B2C e-commerce environment, analyzes the customer's consumer psychology and behavior under B2C environment, and points out the customer retention strategy. This paper has a reference to B2C website.%本文以B2C电子商务交易过程为背景,从客户行为分析的目标出发,提出了基于B2C电子商务环境下的客户行为分析过程,并对B2C环境下的客户消费心理和行为进行了分析,提出了B2C环境下的客户保留策略,这对B2C网站具有借鉴意义.

  9. Discussion on B2B electronic commerce pattern%B2B电子商务模式的探讨

    Institute of Scientific and Technical Information of China (English)

    陈昌

    2007-01-01

    针对B2B模式将成为未来电子商务发展的主流,文章先从价值链角度分析了B2B电子商务模式对价值链上游的冲击,然后概括性地总结了目前主要的3种B2B电子商务模式,最后用"SWOT"战略评估方法分析了基于供应链管理的区域型B2B电子商务新模式.

  10. Activation of kinin B1 receptor evokes hyperthermia through a vagal sensory mechanism in the rat

    Directory of Open Access Journals (Sweden)

    Talbot Sébastien

    2012-09-01

    Full Text Available Abstract Background Kinins are mediators of pain and inflammation. Their role in thermoregulation is, however, unknown despite the fact the B1 receptor (B1R was found implicated in lipopolysaccharide (LPS-induced fever. The aim of this study was to investigate the mechanism by which peripheral B1R affects body core temperature in a rat model known to show up-regulated levels of B1R. Methods Male Sprague–Dawley rats received streptozotocin (STZ, 65 mg/kg; i.p. to enhance B1R expression. Control rats received the vehicle only. One week later, rectal temperature was measured in awake rats after i.p. injection of increasing doses (0.01 to 5 mg/kg of des-Arg9-Bradykinin (BK and Sar-[D-Phe8]des-Arg9-BK (B1R agonists or BK (B2R agonist. The mechanism of B1R-induced hyperthermia was addressed using specific inhibitors and in rats subjected to subdiaphragmatic vagal nerve ligation. B1R mRNA level was measured by quantitative Real Time-polymerase chain reaction (qRT-PCR and B1R was localized by confocal microscopy. Results B1R agonists (0.1 to 5 mg/kg showed transient (5- to 30-minute and dose-dependent increases of rectal temperature (+1.5°C in STZ-treated rats, but not in control rats. BK caused no effect in STZ and control rats. In STZ-treated rats, B1R agonist-induced hyperthermia was blocked by antagonists/inhibitors of B1R (SSR240612, cyclooxygenase-2 (COX-2 (niflumic acid and nitric oxide synthase (NOS (L-NAME, and after vagal nerve ligation. In contrast, COX-1 inhibition (indomethacin had no effect on B1R agonist-induced hyperthermia. In STZ-treated rats, B1R mRNA was significantly increased in the hypothalamus and the vagus nerve where it was co-localized with calcitonin-gene-related peptide in sensory C-fibers. Conclusion B1R, which is induced in inflammatory diseases, could contribute to hyperthermia through a vagal sensory mechanism involving prostaglandins (via COX-2 and nitric oxide.

  11. Phonon linewidths in YNi2B2C

    Indian Academy of Sciences (India)

    L Pintschovius; F Weber; W Reichardt; A Kreyssig; R Heid; D Reznik; O Stockert; K Hradil

    2008-10-01

    Phonons in a metal interact with conduction electrons which give rise to a finite linewidth. In the normal state, this leads to a Lorentzian shape of the phonon line. Density functional theory is able to predict the phonon linewidths as a function of wave vector for each branch of the phonon dispersion. An experimental verification of such predictions is feasible only for compounds with very strong electron–phonon coupling. YN2B2C was chosen as a test example because it is a conventional superconductor with a fairly high c (15.2 K). Inelastic neutron scattering experiments did largely confirm the theoretical predictions. Moreover, they revealed a strong temperature dependence of the linewidths of some phonons with particularly strong electron–phonon coupling which can as yet only qualitatively be accounted for by theory. For such phonons, marked changes of the phonon frequencies and linewidths were observed from room temperature down to 15 K. Further changes were observed on entering into the superconducting state. These changes can, however, not be described simply by a change of the phonon linewidth.

  12. Electronic structure and superconductivity of MgB2

    Indian Academy of Sciences (India)

    D M Gaitonde; P Modak; R S Rao; B K Godwal

    2003-01-01

    Results of ab initio electronic structure calculations on the compound, MgB2, using the FPLAPW method employing GGA for the exchange–correlation energy are presented. Total energy minimization enables us to estimate the equilibrium volume, / ratio and the bulk modulus, all of which are in excellent agreement with experiment. We obtain the mass enhancement parameter by using our calculated, $D(E_F)$ and the experimental specific heat data. The $T_c$ is found to be 37 K. We use a parametrized description of the calculated band structure to obtain the = 0 K values of the London penetration depth and the superconducting coherence length. The penetration depth calculated by us is too small and the coherence length too large as compared to the experimentally determined values of these quantities. This indicates the limitations of a theory that relies only on electronic structure calculations in describing the superconducting state in this material and implies that impurity effects as well as mass renormalization effects need to be included.

  13. The Methane Abundance in Comet Hyakutake (C/1996 B2)

    Science.gov (United States)

    Weaver, H. A.; Brooke, T. Y.; Disanti, M. A.; Mumma, M. J.; Tokunaga, A.; Chin, G.; A'Hearn, M. F.; Owen, T. C.; Lisse, C. M.

    1997-07-01

    We report on infrared observations of methane in comet Hyakutake (C/1996 B2) that were obtained during April 1996 using CSHELL at the NASA IRTF. The effective aperture size was 1'' x 2'' and the spectral resolving power was ~ 20,000. On 8-9 April we observed at r=0.73-0.71 AU and Delta =0.47-0.50 AU, while on 16 April r=0.54 AU and Delta =0.73 AU. Seven different lines in the nu_ {3} band near 3.3 mu m were clearly detected, and we have used their relative intensities to conduct the first detailed examination of the rotational excitation in cometary methane. We derive a rotational temperature (Trot) of ~ 110 K on 8-9 April and ~ 150 K on 16 April, which indicates that Trot varied approximately inversely with the heliocentric distance. We also find that the population distribution among the different spin species is consistent with the value expected in the high temperature limit (Tspin>=50 K). We estimate that the methane abundance relative to water was ~ 1% during the period of our observations, although this value is uncertain by at least a factor of two due to uncertainties in the water production rate. Methane is apparently an important trace constituent of both cometary nuclei and grain mantles in star-forming regions, which provides further evidence that comets retain a signature of their interstellar heritage.

  14. Effects of neutron irradiation on polycrystalline Mg11B2

    International Nuclear Information System (INIS)

    We studied the influence of the disorder introduced in polycrystalline MgB2 samples by neutron irradiation. To circumvent self-shielding effects due to the strong interaction between thermal neutrons and 10B we employed isotopically enriched 11B which contains 40 times less 10B than natural B. The comparison of electrical and structural properties of different series of samples irradiated in different neutron sources, also using Cd shields, allowed us to conclude that, despite the low 10B content, the main damage mechanisms are caused by thermal neutrons, whereas fast neutrons play a minor role. Irradiation leads to an improvement in both upper critical field and critical current density for an exposure level in the range 1-2x1018 cm-2. With increasing fluence the superconducting properties are depressed. An in-depth analysis of the critical field and current density behavior has been carried out to identify what scattering and pinning mechanisms come into play. Finally, the correlation between some characteristic lengths and the transition widths is analyzed

  15. Microwave surface impedance of MgB2 thin film

    International Nuclear Information System (INIS)

    The microwave surface impedance Zs = Rs + jωμ0λ was measured with dielectric resonator techniques for two c-axis-oriented MgB2 thin films. The temperature dependence of the penetration depth λ measured with a sapphire resonator at 17.93 GHz can be well fitted from 5 K close to Tc by the standard BCS integral expression assuming the reduced energy gap Δ(0)/kTc to be as low as 1.13 and 1.03 for the two samples. From these fits the penetration depth at zero temperatures was determined to be 102 nm and 107 nm, respectively. The results clearly indicate the s-wave nature of the order parameter. The temperature dependence of surface resistance Rs, measured with a rutile dielectric resonator, shows an exponential behaviour below about Tc/2 with a reduced energy gap being consistent with the one determined from the λ data. The Rs value at 4.2 K was found to be as low as 19 μΩ at 7.2 GHz, which is comparable with that of a high-quality high-temperature thin film of YBa2Cu3O7. A higher-order mode at 17.9 GHz was employed to determine the frequency f dependence of Rs ∝ fn(T). Our results revealed a decrease of n with increasing temperature ranging from n = 2 below 8 K to n 1 from 13 to 34 K

  16. Lightweight MgB2 superconducting 10 MW wind generator

    Science.gov (United States)

    Marino, I.; Pujana, A.; Sarmiento, G.; Sanz, S.; Merino, J. M.; Tropeano, M.; Sun, J.; Canosa, T.

    2016-02-01

    The offshore wind market demands a higher power rate and more reliable turbines in order to optimize capital and operational costs. The state-of-the-art shows that both geared and direct-drive conventional generators are difficult to scale up to 10 MW and beyond due to their huge size and weight. Superconducting direct-drive wind generators are considered a promising solution to achieve lighter weight machines. This work presents an innovative 10 MW 8.1 rpm direct-drive partial superconducting generator using MgB2 wire for the field coils. It has a warm iron rotor configuration with the superconducting coils working at 20 K while the rotor core and the armature are at ambient temperature. A cooling system based on cryocoolers installed in the rotor extracts the heat from the superconducting coils by conduction. The generator's main parameters are compared against a permanent magnet reference machine, showing a significant weight and size reduction. The 10 MW superconducting generator concept will be experimentally validated with a small-scale magnetic machine, which has innovative components such as superconducting coils, modular cryostats and cooling systems, and will have similar size and characteristics as the 10 MW generator.

  17. Herschel observations of deuterated water towards Sgr B2(M)

    CERN Document Server

    Comito, Claudia; Rolffs, Rainer; Lis, D C; Belloche, A; Bergin, E A; Phillips, T G; Bell, T A; Crockett, N R; Wang, S; Blake, G A; Caux, E; Ceccarelli, C; Cernicharo, J; Daniel, F; Dubernet, M -L; Emprechtinger, M; Encrenaz, P; Gerin, M; Giesen, T F; Goicoechea, J R; Goldsmith, P F; Gupta, H; Herbst, E; Joblin, C; Johnstone, D; Langer, W D; Latter, W D; Lord, S D; Maret, S; Martin, P G; Melnick, G J; Menten, K M; Morris, P; Mueller, H S P; Murphy, J A; Neufeld, D A; Ossenkopf, V; Pearson, J C; Perault, M; Plume, R; Qin, S -L; Schlemmer, S; Stutzki, J; Trappe, N; van der Tak, F F S; Vastel, C; Yorke, H W; Yu, S; Olberg, M; Szczerba, R; Larsson, B; Liseau, R; Lin, R H; Samoska, L A; Schlecht, E

    2010-01-01

    Observations of HDO are an important complement for studies of water, because they give strong constraints on the formation processes -- grain surfaces versus energetic process in the gas phase, e.g. in shocks. The HIFI observations of multiple transitions of HDO in Sgr~B2(M) presented here allow the determination of the HDO abundance throughout the envelope, which has not been possible before with ground-based observations only. The abundance structure has been modeled with the spherical Monte Carlo radiative transfer code RATRAN, which also takes radiative pumping by continuum emission from dust into account. The modeling reveals that the abundance of HDO rises steeply with temperature from a low abundance ($2.5\\times 10^{-11}$) in the outer envelope at temperatures below 100~K through a medium abundance ($1.5\\times 10^{-9}$) in the inner envelope/outer core, at temperatures between 100 and 200~K, and finally a high abundance ($3.5\\times 10^{-9}$) at temperatures above 200~K in the hot core.

  18. Convergent Evolution of Head Crests in Two Domesticated Columbids Is Associated with Different Missense Mutations in EphB2.

    Science.gov (United States)

    Vickrey, Anna I; Domyan, Eric T; Horvath, Martin P; Shapiro, Michael D

    2015-10-01

    Head crests are important display structures in wild bird species and are also common in domesticated lineages. Many breeds of domestic rock pigeon (Columba livia) have crests of reversed occipital feathers, and this recessive trait is associated with a nonsynonymous coding mutation in the intracellular kinase domain of EphB2 (Ephrin receptor B2). The domestic ringneck dove (Streptopelia risoria) also has a recessive crested morph with reversed occipital feathers, and interspecific crosses between crested doves and pigeons produce crested offspring, suggesting a similar genetic basis for this trait in both species. We therefore investigated EphB2 as a candidate for the head crest phenotype of ringneck doves and identified a nonsynonymous coding mutation in the intracellular kinase domain that is significantly associated with the crested morph. This mutation is over 100 amino acid positions away from the crest mutation found in rock pigeons, yet both mutations are predicted to negatively affect the function of ATP-binding pocket. Furthermore, bacterial toxicity assays suggest that "crest" mutations in both species severely impact kinase activity. We conclude that head crests are associated with different mutations in the same functional domain of the same gene in two different columbid species, thereby representing striking evolutionary convergence in morphology and molecules. PMID:26104009

  19. TiB2 nanostructured coating for GFRP injection moulds.

    Science.gov (United States)

    Martinho, R P; Silva, F J G; Alexandre, R J D; Baptista, A P M

    2011-06-01

    In the injection moulding of polypropylene reinforced with hard glass fibres, die materials are commonly subjected to severe abrasive wear. In order to improve its wear resistance, an unbalanced magnetron sputtering PVD compositional monolayered coating has been produced. The film was composed by a nanostructured TiB2 monolayer. Microstructure characterization and thickness evaluation were conducted by scanning electron microscopy (SEM). Film topography and roughness were accessed by SEM and Atomic Force Microscopy (AFM). The phase analyse was investigated by X-ray diffraction (XRD), using Cu Kalpha radiation. Scratch tests were conducted in order to study the film adhesion to the substrate. Load-Displacement curves (nanoindentation analysis) allowed measuring the film hardness and Young's modulus. A ball-cratering tribometer was used to determine the micro-abrasion laboratorial wear resistance, under different tests conditions, using SiC particles in distilled water slurry. At the end of these tests, the worn surfaces were analyzed by SEM and Energy Dispersive X-ray Spectroscopy (EDS) in order to compare these results with some other coatings already tested in the same conditions. To test the practical wear resistance, 135000 injection cycles were done in a plastic injection industrial mould. Coated samples were put on the plastic feed canal, after a turbulent zone. In these tests, a 30% (wt) glass fibres reinforced polypropylene was used. Worn sample surfaces were analyzed by SEM after 45.000 and 90.000 cycles. Image analyses were made in order to evaluate the damage increases and to observe the wear mechanisms involved. PMID:21770191

  20. Hot corrosion of the B2 nickel aluminides

    Science.gov (United States)

    Ellis, David L.

    1993-01-01

    The hot corrosion behavior of the B2 nickel aluminides was studied to determine the inherent hot corrosion resistance of the beta nickel aluminides and to develop a mechanism for the hot corrosion of the beta nickel aluminides. The effects of the prior processing of the material, small additions of zirconium, stoichiometry of the materials, and preoxidation of the samples were also examined. Additions of 2, 5, and 15 w/o chromium were used to determine the effect of chromium on the hot corrosion of the beta nickel aluminides and the minimum amount of chromium necessary for good hot corrosion resistance. The results indicate that the beta nickel aluminides have inferior inherent hot corrosion resistance despite their excellent oxidation resistance. Prior processing and zirconium additions had no discernible effect on the hot corrosion resistance of the alloys. Preoxidation extended the incubation period of the alloys only a few hours and was not considered to be an effective means of stopping hot corrosion. Stoichiometry was a major factor in determining the hot corrosion resistance of the alloys with the higher aluminum alloys having a definitely superior hot corrosion resistance. The addition of chromium to the alloys stopped the hot corrosion attack in the alloys tested. From a variety of experimental results, a complex hot corrosion mechanism was proposed. During the early stages of the hot corrosion of these alloys the corrosion is dominated by a local sulphidation/oxidation form of attack. During the intermediate stages of the hot corrosion, the aluminum depletion at the surface leads to a change in the oxidation mechanism from a protective external alumina layer to a mixed nickel-aluminum spinel and nickel oxide that can occur both externally and internally. The material undergoes extensive cracking during the later portions of the hot corrosion.

  1. 17 CFR 240.13b2-1 - Falsification of accounting records.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Falsification of accounting records. 240.13b2-1 Section 240.13b2-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE... Required Reports § 240.13b2-1 Falsification of accounting records. No person shall directly or...

  2. 26 CFR 20.2056(b)-2 - Marital deduction; interest in unidentified assets.

    Science.gov (United States)

    2010-04-01

    ... assets. 20.2056(b)-2 Section 20.2056(b)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... Taxable Estate § 20.2056(b)-2 Marital deduction; interest in unidentified assets. (a) In general. Section... of assets (or their proceeds) which include a particular asset that would be a nondeductible...

  3. Lapatinib in combination with capecitabine in the management of ErbB2-positive (HER2-positive advanced breast cancer

    Directory of Open Access Journals (Sweden)

    Bella Kaufman

    2008-03-01

    Full Text Available Bella Kaufman1, Steven Stein2, Michelle A Casey2, Beth O Newstat21Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; 2GlaxoSmithKline, Collegeville, PA, USAAbstract: Lapatinib is an oral, reversible, dual inhibitor of epidermal growth factor receptor ErbB1 (EGFR and human epidermal growth factor receptor type 2 ErbB2 (HER2. Results of a phase III study comparing lapatinib plus capecitabine with capecitabine alone in women with ErbB2-overexpressing advanced breast cancer previously treated with an anthracycline, a taxane, and trastuzumab were reported early based on superiority of the combination in prolonging time to tumor progression (TTP. An updated analysis in 399 women supports the earlier findings. In this updated analysis, TTP (hazard ratio [HR] 0.57 favored lapatinib plus capecitabine. Survival trended in favor of the combination. The incidence of cardiac events was numerically higher in the combination arm (5 cases in the combination arm, 2 cases in the monotherapy arm.Keywords: lapatinib, capecitabine, breast cancer, HER2

  4. CCD SURFACE PHOTOMETRY OF THE LOW-LUMINOSITY RADIO GALAXIES CONTAINING RADIO JETS B-2-0034+25 AND B-2-0206+35

    NARCIS (Netherlands)

    GONZALEZSERRANO, JI; PEREZFOURNON, [No Value

    1991-01-01

    We present broad-band CCD imaging of the radio galaxies B2 0034+25 and B2 0206+36. Both galaxies are of low radio power and contain radio jets at the arcsec scale. The galaxies have close companions and the optical morphology suggests that they are interacting. The surface photometry method and its

  5. Novel pharmaceutical composition of bradykinin potentiating penta peptide with beta-cyclodextrin: physical-chemical characterization and anti-hypertensive evaluation.

    Science.gov (United States)

    Denadai, Angelo M L; Ianzer, Danielle; Alcântara, Antônio Flávio de C; Santoro, Marcelo M; Santos, Cynthia F F; Lula, Ivana Silva; de Camargo, Antônio C M; Faljoni-Alario, Adelaide; dos Santos, Robson A S; Sinisterra, Rubén D

    2007-05-01

    This work describes chemical properties and anti-hypertensive activity of an oral pharmaceutical formulation obtained from the complexation of beta-cyclodextrin (beta-CD) with bradykinin potentiating penta peptide (BPP-5a) founded in the Bothrops jararaca poison. Physical chemistry characterizations were recorded in order to investigate the intermolecular interactions between species in complex. Circular dichroism data indicated conformational changes of BPP-5a upon complexation with beta-CD. ROESY and theoretical calculations showed a selective approximation of triptophan moiety into cavity of beta-CD. Isothermal titration calorimetry data indicated an exothermic formation of the complex, which is accomplished by reduction of entropy. The anti-hypertensive activity of the BPP-5a/beta-CD complex has been evaluated in spontaneous hypertensive rats, showing better results than pure BPP-5a. PMID:17196774

  6. Vortex phase diagram studies in the weakly pinned single crystals of YNi2B2C and LuNi2B2C

    Indian Academy of Sciences (India)

    D Jaiswal-Nagar; D Pal; M R Eskildsen; P C Canfield; H Takeya; S Ramakrishnan; A K Grover

    2006-01-01

    We present a study of magnetization measurements performed on the single crystals of YNi2B2C and LuNi2B2C. For both the compounds, we find flux jumps in magnetisation values in the respective field regions, where the structural transitions in the flux line lattice symmetry have been reported in these systems via the small angle neutron scattering experiments. The magnetisation hysteresis loops and the AC susceptibility measurements show pronounced peak effect as well as second magnetisation peak anomaly for both YNi2B2C and LuNi2B2C. Based on these results, a vortex phase diagram has been constructed for YNi2B2C for $H \\Arrowvert c$ depicting different glassy phases of the vortex matter.

  7. Doping effects of ZrC and ZrB2 in the powder-in-tube processed MgB2 tapes

    Institute of Scientific and Technical Information of China (English)

    MA Yanwei

    2006-01-01

    We have investigated the effects of ZrC and ZrB2 doping on the superconducting properties of the powder-in-tube processed MgB2/Fe tapes. Samples were characterized by X-ray diffraction (XRD),scanning electron microscopy (SEM/EDX), transport and magnetic measurements. We confirmed the following quite different roles of ZrC and ZrB2 in MgB2.ZrC doping was found to decrease the transport critical current density (Jc) at 4.2 K, while the critical temperature (Tc) kept constant. In contrast, the Jc values in magnetic fields were enhanced greatly by the ZrB2 addition, which resulted in a decrease in Tc by only 0.5 K. The reason for different effects of two dopants is also discussed.

  8. Synergistic Effect of Bone Marrow Transplantation and Bradykinin Potential Factor Isolated from Venom on Thymus and Spleen of Sublethally Irradiated Guinea Pigs

    International Nuclear Information System (INIS)

    The buthus occitanus, scorpion venom contains a strong bradykinin potentiating factor (BPF) that augments bradykinin effects through enhancing its release. Based on the cytoprotective ability of BPF, the present work investigates it as a radioprotectant. Sublethal whole-body y-irradiation at 1.5 Gy was used. Bone marrow cells suspension (BM cells) alone or in combination with BPF was utilized. Three to four weeks-aged male Guinea pigs were grouped into two major groups. The first was non-irradiated control that was divided into subgroups treated i.p. with BM cells (2.5xl06 cells), one dose of BPF (lug/g b wt), BM cells+ BPF, one week spaced two doses of BPF, BM cells+ 2 doses of BPF, one week spaced three doses of BPF or BM cells+ 3 doses of BPF. Second major group (irradiated group) at 1.5 Gy that, subdivided and treated similarly. 5 animals from each group were killed at 7, 14 and 21 days from the initiation of treatment (3 h after irradiation). The subgroups of non-irradiated animals showed an increase in spleen wt and colony formation, thymus population, and globulins content particularly in those subgroups that stayed for the later time periods (14 and 21 days) and that treated with combined BM cells+ BPF or that groups that were treated with two or three BPF doses. Irradiation caused dramatic destruction in thymus and the spleen reflected on reduction of the lower globulins content. Treatment with BM cells, BM cells+ double doses of BPF or triple doses of BPF caused complete recovery in all measured indices, the best result was observed in those of subgroups treated with BM cells+ double doses of BPF or treated with triple doses of BPF. They completely normalized the investigated parameters after 14 and 21 days respectively

  9. In silico structure-function analysis of pathological variation in the HSD11B2 gene sequence.

    Science.gov (United States)

    Manning, Jonathan R; Bailey, Matthew A; Soares, Dinesh C; Dunbar, Donald R; Mullins, John J

    2010-08-01

    11beta-Hydroxysteroid dehydrogenase type 2 (11betaHSD2) is a short-chain dehydrogenase/reductase (SDR) responsible for inactivating cortisol and preventing its binding to the mineralocorticoid receptor (MR). Nonfunctional mutations in HSD11B2, the gene encoding 11betaHSD2, cause the hypertensive syndrome of apparent mineralocorticoid excess (AME). Like other such Mendelian disorders, AME is rare but has nevertheless helped to illuminate principles fundamental to the regulation of blood pressure. Furthermore, polymorphisms in HSD11B2 have been associated with salt sensitivity, a major risk factor for cardiovascular mortality. It is therefore highly likely that sequence variation in HSD11B2, having subtle functional ramifications, will affect blood pressure in the wider population. In this study, a three-dimensional homology model of 11betaHSD2 was created and used to hypothesize the functional consequences in terms of protein structure of published mutations in HSD11B2. This approach underscored the strong genotype-phenotype correlation of AME: severe forms of the disease, associated with little in vivo enzyme activity, arise from mutations occurring in invariant alignment positions. These were predicted to exert gross structural changes in the protein. In contrast, those mutations causing a mild clinical phenotype were in less conserved regions of the protein that were predicted to be relatively more tolerant to substitution. Finally, a number of pathogenic mutations are shown to be associated with regions predicted to participate in dimer formation, and in protein stabilization, which may therefore suggest molecular mechanisms of disease. PMID:20571110

  10. Effect of Nano Scale Fe Doping on Superconducting Properties of MgB2

    OpenAIRE

    S. X. Dou; Soltanian, S.; Zhao, Y.; Getin, E.; Chen, Z.; Horvat, J.

    2004-01-01

    Iron is an important sheath material for fabrication of MgB2 wires. However, the effect of Fe doping on the superconducting properties of MgB2 remains controversial. In this work, we present results of nano-scale Fe particle doping in to MgB2. The Fe doping experiments were performed using both bulk and thin film form. It was found that Fe doping did not affect the lattice parameters of MgB2, as evidenced by the lack of change in the XRD peak positions for MgB2. Because of the high reactivity...

  11. B2B电子商务网站分类新探索

    Institute of Scientific and Technical Information of China (English)

    谢启燕

    2010-01-01

    B2B电子商务是电子商务的主流,发展前景可观.B2B电子商务网站每年呈快速增长趋势,要研究B2B电子商务网的发展规律和发展方向,我们应将从更深的维度和不同的角度来分类和分析B2B电子商务网站.由此文章分析了三种B2B电子商务网站新分类.

  12. Analysis of the Role of Social Media in B2B Marketing for Startups

    OpenAIRE

    Fomicheva, Yekaterina

    2015-01-01

    Social media is a new, yet very prominent concept in present marketing communication. It has been growing steadily and became popular among marketers both in business-to-customer (B2C) and business-to-business (B2B). However, there has been more research done on how to apply and utilize social media in the B2C scenario and there are fewer explanations about B2B cases. Therefore, it was interesting to do research and analysis on how B2B companies operate, what are the factors influencing socia...

  13. Neuregulin-1-mediated ErbB2–ErbB3 signalling protects human trophoblasts against apoptosis to preserve differentiation

    Science.gov (United States)

    Fock, Valerie; Plessl, Kerstin; Draxler, Peter; Otti, Gerlinde Regina; Fiala, Christian; Knöfler, Martin; Pollheimer, Jürgen

    2015-01-01

    ABSTRACT During placentation, foetal trophoblasts invade deeply into maternal tissue to establish a foeto–maternal circulation. We have previously shown that extravillous trophoblast (EVT) lineage cells express ErbB2 and ErbB3, of which the potential as an oncogenic unit is well established. However, a physiological function of this receptor combination in humans remains a puzzling question. Here, we demonstrate neuregulin 1 (NRG1) expression and secretion by human decidual stromal cells. Stimulation of human primary trophoblasts with exogenous NRG1 induced phosphorylation of ErbB2, ErbB3 and related downstream effectors. Co-immunoprecipitation experiments confirmed the formation of ErbB2–ErbB3 dimers upon ligand engagement. Along this line, receptor knockdown and ErbB3 neutralization strongly diminished NRG1-dependent activation of the signalling complex. Functional studies revealed that NRG1 promotes EVT formation in placental explant cultures. Although, in the presence of NRG1, basal and camptothecin-induced trophoblast apoptosis was significantly repressed, this effect was abolished upon ErbB3 inhibition. Notably, camptothecin provoked a strong reduction of trophoblast cell column size, whereas NRG1-treated explants were refractory to the compound. Taken together, our findings newly identify a physiological function of the NRG1–ErbB2–ErbB3 axis in trophoblast survival during human placental development. PMID:26490994

  14. Naked Polyamidoamine Polymers Intrinsically Inhibit Angiotensin II-Mediated EGFR and ErbB2 Transactivation in a Dendrimer Generation- and Surface Chemistry-Dependent Manner.

    Science.gov (United States)

    Akhtar, Saghir; El-Hashim, Ahmed Z; Chandrasekhar, Bindu; Attur, Sreeja; Benter, Ibrahim F

    2016-05-01

    The effects of naked polyamidoamine (PAMAM) dendrimers on renin-angiotensin system (RAS) signaling via Angiotensin (Ang) II-mediated transactivation of the epidermal growth factor receptor (EGFR) and the closely related family member ErbB2 (HER2) were investigated. In primary aortic vascular smooth muscle cells, a cationic fifth-generation (G5) PAMAM dendrimer dose- and time-dependently inhibited Ang II/AT1 receptor-mediated transactivation of EGFR and ErbB2 as well as their downstream signaling via extracellular-regulated kinase 1/2 (ERK1/2). Inhibition even occurred at noncytotoxic concentrations at short (1 h) exposure times and was dependent on dendrimer generation (G7 > G6 > G5 > G4) and surface group chemistry (amino > carboxyl > hydroxyl). Mechanistically, the cationic G5 PAMAM dendrimer inhibited Ang II-mediated transactivation of EGFR and ErbB2 via inhibition of the nonreceptor tyrosine kinase Src. This novel, early onset, intrinsic biological action of PAMAM dendrimers as inhibitors of the Ang II/AT1/Src/EGFR-ErbB2/ERK1/2 signaling pathway could have important toxicological and pharmacological implications. PMID:26985693

  15. Structure and microtribological characteristics of laser-arc deposited TiB2 thin film

    Institute of Scientific and Technical Information of China (English)

    CAO Xiankun; SHAO Tianmin; WEN Shizhu; QING Tao; QI Feng

    2004-01-01

    TiB2 thin film was deposited by laser-arc deposition method on the surface of single crystalline silicon. The morphology, composition, structure and microtribological properties of the film were studied by using XPS, XRD and atomic force/friction force microscope (AFM/FFM). The results show that TiB2 (100) preferred growth on the Si(100)substrate, TiB2(001) preferred growth on the Si(111) substrate. The TiB2 thin film was composed of TiB2 and a small amount of TiO2. The friction coefficient of TiB2 film on substrates Si (100) and Si(111) in microtribological process were 0.087 and 0.073,respectively. TiB2 thin film displayed distinct ability of anti-scratch and wear-resistance.

  16. Microstructure and mechanical properties investigation of in situ TiB2 and ZrB2 reinforced Al-4Cu composites

    Science.gov (United States)

    Lutfi Anis, Ahmad; Ramli, Rosmamuhammadani; Darham, Widyani; Zakaria, Azlan; Talari, Mahesh Kumar

    2016-02-01

    Conventional Al-Cu alloys exhibit coarse grain structure leading to inferior mechanical properties in as-cast condition. Expensive thermo-mechanical treatments are needed to improve microstructure and corresponding mechanical properties. In situ Al-based composites were developed to improve mechanical properties by dispersion strengthening and grain refinement obtained by the presence of particulates in the melt during solidification. In this work Al-4Cu - 3TiB2 and Al-4Cu-3ZrB2 in situ composites were prepared by liquid casting method. XRD, electron microscopy and mechanical tests were performed on suitably sectioned and metallographically prepared surfaces to investigate the phase distribution, hardness and tensile properties. It was found that the reinforcement particles were segregated along the grain boundaries of Al dendrites. Tensile fracture morphology for both Al-4Cu - 3TiB2 and Al-4Cu-3ZrB2 were analyzed and compared to determine the fracture propagation mechanism in the composites. Al-4Cu-3ZrB2 in situ composites displayed higher strength and hardness compared to Al-4Cu-3TiB2 which could be ascribed to the stronger interfacial bonding between the Al dendrites and ZrB2 particulates as evidenced from fractographs.

  17. BPO4@B2O3 and (BPO4@B2O3):Eu3+: The novel single-emitting-component phosphors for near UV-white LEDs

    Science.gov (United States)

    Cao, Xiyu; Liu, Wei; Jiang, Yu; Cao, Lixin; Su, Ge; Gao, Rongjie

    2016-08-01

    Nowadays much effort has been devoted to exploring novel luminescent materials with low-cost, high stability and excellent luminescent properties. In this paper, a new kind of luminescent material BPO4@B2O3 was prepared by using a facile method. The as-obtained samples contain numerous BPO4 nanoparticles enclosed by amorphous and crystalline B2O3 homogeneously, which exhibits a broad emission band ranging from 380 to 700 nm under near-UV irradiation. More importantly, it is worth noting that the BPO4@B2O3 phosphor exhibits the excellent thermal quenching property, which endows it with a promising prospect as phosphors for high power white LEDs. To further promote its application as white light phosphors, Eu3+ ions were doped into the BPO4@B2O3 samples and prepared the (BPO4@B2O3):Eu3+ phosphors with chromaticity coordinates (0.3022, 0.3122). The corresponding packaging of LEDs indicates that both BPO4@B2O3 and (BPO4@B2O3):Eu3+ can be considered as the promising phosphors for WLEDs.

  18. Secretion of SerpinB2 from endothelial cells activated with inflammatory stimuli

    Energy Technology Data Exchange (ETDEWEB)

    Boncela, Joanna; Przygodzka, Patrycja [Institute of Medical Biology, Polish Academy of Sciences, Lodz (Poland); Wyroba, Elzbieta [Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw (Poland); Papiewska-Pajak, Izabela [Department of Molecular and Medical Biophysics, Medical University of Lodz (Poland); Cierniewski, Czeslaw S., E-mail: czeslaw.cierniewski@umed.lodz.pl [Institute of Medical Biology, Polish Academy of Sciences, Lodz (Poland); Department of Molecular and Medical Biophysics, Medical University of Lodz (Poland)

    2013-05-01

    Due to the lack of an N-terminal signal peptide, SerpinB2 (plasminogen activator inhibitor type 2) accumulates in cells and only a small percentage of it is secreted. The extracellular concentration of SerpinB2 significantly increases during inflammation. In the present study we investigated the mechanism with which SerpinB2 can be secreted from endothelial cells activated with LPS. We evaluated the intracellular distribution of SerpinB2 by double immunogold labeling followed by a high resolution electron microscopy analysis. We found that SerpinB2 gathers in the vesicular structures and in the endothelial cell periphery. These vesicles stained positive for the trans-Golgi network marker TGN46, which is consistent with their formation by the endoplasmatic reticulum (ER) and Golgi-dependent pathways. SerpinB2 was delivered to the plasma membrane, apparently together with TGN46 in the same vesicles, which after fusion with the membranes released cargo. Secretion of SerpinB2 was partially inhibited by brefeldin A. The secreted SerpinB2 was predominantly in its nonglycosylated 43 kDa form as evaluated by Western immunoblotting. Our data suggest that increased expression of SerpinB2 by an inflammatory stimulus is sufficient to generate structures that resemble secretory vesicles. These vesicles may represent the mechanism by which high local concentrations of SerpinB2 are released at inflammation sites from endothelial cells. - Highlights: ► LPS stimulates generation of secretory vesicles containing SerpinB2. ► SerpinB2 concentrates in TGN46 positive vesicles close to the plasma membrane. ► Brefeldin A inhibits secretion of SerpinB2. ► The secreted SerpinB2 was predominantly in its nonglycosylated 43 kDa.

  19. Secretion of SerpinB2 from endothelial cells activated with inflammatory stimuli

    International Nuclear Information System (INIS)

    Due to the lack of an N-terminal signal peptide, SerpinB2 (plasminogen activator inhibitor type 2) accumulates in cells and only a small percentage of it is secreted. The extracellular concentration of SerpinB2 significantly increases during inflammation. In the present study we investigated the mechanism with which SerpinB2 can be secreted from endothelial cells activated with LPS. We evaluated the intracellular distribution of SerpinB2 by double immunogold labeling followed by a high resolution electron microscopy analysis. We found that SerpinB2 gathers in the vesicular structures and in the endothelial cell periphery. These vesicles stained positive for the trans-Golgi network marker TGN46, which is consistent with their formation by the endoplasmatic reticulum (ER) and Golgi-dependent pathways. SerpinB2 was delivered to the plasma membrane, apparently together with TGN46 in the same vesicles, which after fusion with the membranes released cargo. Secretion of SerpinB2 was partially inhibited by brefeldin A. The secreted SerpinB2 was predominantly in its nonglycosylated 43 kDa form as evaluated by Western immunoblotting. Our data suggest that increased expression of SerpinB2 by an inflammatory stimulus is sufficient to generate structures that resemble secretory vesicles. These vesicles may represent the mechanism by which high local concentrations of SerpinB2 are released at inflammation sites from endothelial cells. - Highlights: ► LPS stimulates generation of secretory vesicles containing SerpinB2. ► SerpinB2 concentrates in TGN46 positive vesicles close to the plasma membrane. ► Brefeldin A inhibits secretion of SerpinB2. ► The secreted SerpinB2 was predominantly in its nonglycosylated 43 kDa

  20. Tumor promoter and epidermal growth factor stimulate phosphorylation of the c-erbB-2 gene product in MKN-7 human adenocarcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Akiyama, T.; Saito, T.; Ogawara, H.; Toyoshima, K.; Yamamoto, T.

    1988-03-01

    Treatment of human adenocarcinoma MKN-7 cells with epidermal growth factor (EGF) or phorbol tetradecanoate acetate (TPA) stimulated phosphorylation of the c-erbB-2 gene product. EGF induced a rapid increase in phosphotyrosine followed by relatively gradual increases in phosphoserine and phosphothreonine. On the other hand, the TPA-induced increase in phosphorylations occurred exclusively on serine and threonine residues. Tryptic phosphopeptide mapping analysis suggested that treatments with EGF and TPA induced phosphorylation of many common sites in the c-erbB-2 gene product. However, in contrast to TPA, EGF increased the phosphorylation of the c-erbB-2 protein in cells whose protein kinase C had been down-regulated by long-term pretreatment with TPA, suggesting that EGF and TPA induce phosphorylation by different mechanisms. Since the c-erbB-2 gene product did not show detectable EGF-binding activity, phosphorylation of tyrosine of the c-erbB-2 gene product might be catalyzed directly by the EGF receptor kinase that was activated by EGF.

  1. Accumulation of neoplastic traits prior to spontaneous in vitro transformation of rat cholangiocytes determines susceptibility to activated ErbB-2/Neu.

    Science.gov (United States)

    Rozich, Rebecca A; Mills, David R; Brilliant, Kate E; Callanan, Helen M; Yang, DongQin; Tantravahi, Umadevi; Hixson, Douglas C

    2010-12-01

    Cholangiocarcinoma, a severe form of biliary cancer, has a high mortality rate resulting partially from the advanced stage of disease at earliest diagnosis. A better understanding of the progressive molecular and cellular changes occurring during spontaneous cholangiocarcinogenesis is needed to identify potential biomarkers for diagnosis/prognosis or targets for novel therapeutics. Here, we show that with continued passage (p) in vitro, rat bile duct epithelial cells (BDEC) accumulated neoplastic characteristics that by mid-passage (p31-85) included alterations in morphology, increased growth rate, growth factor independence, decreased cell adhesion, loss of cholangiocyte markers expressed at low passage (p85), BDEC cultures showed increasing numbers of cells expressing activated, tyrosine phosphorylated ErbB-2/Neu, a receptor tyrosine kinase previously reported to be at elevated levels in cholangiocarcinomas. Enrichment for high passage ErbB-2/Neu-positive cells yielded several anchorage-independent sub-lines with elevated levels of activated ErbB-2/Neu and increased expression of cyclooxygenase-2 (COX-2). When injected into immunodeficient beige/nude/xid mice, these sub-lines formed poorly differentiated cystic tumors strongly positive for rat cholangiocyte markers, a finding consistent with a previous report showing the susceptibility of high passage, non-tumorigenic BDEC to transformation by activated ErbB-2/Neu. Mid passage BDEC, in contrast, were resistant to the transforming activity of activated ErbB-2/Neu and remained anchorage dependent in vitro and non-tumorigenic in vivo following stable transfection. Based on these findings, we concluded that during progression to high passage, cultured BDEC undergo preneoplastic changes that enhance their susceptibility to transformation by ErbB-2/Neu. The ability to generate cells at different points in the process of spontaneous neoplastic transformation offers a valuable model system for identifying molecular

  2. A report on how foreign trade enterprises use B2B platform%外贸B2B平台使用调查

    Institute of Scientific and Technical Information of China (English)

    李冠艺

    2010-01-01

    @@ 为帮助外贸企业更好地选择外贸B2B平台所提供的服务,用好外贸B2B平台,提高使用效果,2010年5月,我们针对全国的外贸企业进行了网络抽样调查,根据调查结果形成此外贸B2B平台使用调查报告.

  3. Thermoluminescence kinetic parameters of different amount La-doped ZnB2O4

    International Nuclear Information System (INIS)

    The kinetic parameters of 1%, 2%, 3% and 4% La-doped ZnB2O4 phosphors (i.e. ZnB2O4:0.01La, ZnB2O4:0.02La, ZnB2O4:0.03La and ZnB2O4:0.04La) synthesized by nitric acid method have been calculated. Thermoluminescence (TL) glow curves of ZnB2O4:La phosphors after beta-irradiation showed a very well defined main peak having the maximum temperature at around 200 °C and a shoulder peak at around 315 °C with a constant heating rate of 5 °C/s. The kinetic parameters of ZnB2O4:La phosphors TL glow peaks (i.e. order of kinetics (b), activation energies (Ea) and frequency factors (s)) have been determined and evaluated by Computerized Glow Curve Deconvolution (CGCD), and Peak Shape (PS) methods using the glow curve data. From the results, it can conclude that the values of Ea obtained with these methods for ZnB2O4:La phosphors are consistent with each other, but the s values differ considerably. - Highlights: • Calculation of TL kinetic parameters for La-doped ZnB2O4. • La-doped ZnB2O4 was synthesized by nitric acid method. • Well defined main peak at about 200 °C

  4. Preparation and Microstructure of Porous ZrB2 Ceramics Using Reactive Spark Plasma Sintering Method

    Institute of Scientific and Technical Information of China (English)

    YUAN Huiping; LI Junguo; SHEN Qiang; ZHANG Lianmeng

    2015-01-01

    Zirconium oxide (ZrO2) and boron carbide (B4C) were added to ZrB2 raw powders to prepare ZrB2 porous ceramics by reactive spark plasma sintering (RSPS). The reactions between ZrO2 and B4C which produce ZrB2 and gas (such as CO and B2O3) result in pore formation. X-Ray Diffraction results indicated that the products phase was ZrB2 and the reaction was completed after the RSPS process. The porosity could be controlled by changing the ratio of synthesized ZrB2 to raw ZrB2 powders. The porosity of porous ceramics with 20 wt% and 40 wt% synthsized ZrB2 are 0.185 and 0.222, respectivly. And dense ZrB2-SiC ceramic with a porosity of 0.057 was prepared under the same conditions for comparison. The pores were homogeneously distributed within the microstructure of the porous ceramics. The results indicate a promising method for preparing porous ZrB2-based ceramics.

  5. Genetic variation and gender determine bradykinin type 1 receptor responses in human tissue: Implications for the ACE-inhibitor-induced effects in patients with coronary artery disease

    NARCIS (Netherlands)

    H. Wu (Haiyan); A.J.M. Roks (Anton); F.P.J. Leijten (Frank); I.M. Garrelds (Ingrid); U. Musterd-Bhaggoe (Usha); A. van den Bogaerdt (Antoon); M.P.M. de Maat (Moniek); M.L. Simoons (Maarten); A.H.J. Danser (Jan); H. Oeseburg (Hisko)

    2014-01-01

    textabstractThe efficacy of the ACE (angiotensin-converting enzyme) inhibitor perindopril in coronary artery disease [EUROPA (European trial on reduction of cardiac events with perindopril in stable coronary artery disease) study] is associated with the rs12050217 A/G single nucleotide polymorphism

  6. First-principles studies for the stability of a graphene-like boron layer on CrB2(0001) and MoB2(0001)

    International Nuclear Information System (INIS)

    With extensive first-principles density-functional-theory calculations, we investigate the stability and the atomic and electronic structures of the CrB2(0001) and MoB2(0001) surfaces, each with two different terminations. It is found that the boron-terminated surface is energetically more favorable over the wide range of thermodynamically allowed chemical potentials than the metal-terminated surface for both CrB2(0001) and MoB2(0001), suggesting a stable layer of graphene-like boron on the surfaces. Our results also show the similarities and the differences in relaxation and in bonding characteristics between the boron-terminated and metal-terminated surfaces.

  7. 关于B2B服务品牌忠诚度的研究%A research on brand loyalty of B2B service

    Institute of Scientific and Technical Information of China (English)

    孔令明; 耿禧则

    2012-01-01

    The research on brand loyalty has been confined to the product brand in the past. This paper applied brand loyalty theory to B2B service brand. Through empirical research, this paper reflected the effect of the brand recognition and brand image to action loyalty and attitude loyalty, and put forward some suggestions for the B2B service brand management%对于品牌忠诚度的研究,过去一直局限于产品品牌上。本文将品牌忠诚度理论运用于B2B服务品牌,通过实证调查,研究品牌认知度与品牌形象对态度忠诚度和行动忠诚度的影响作用,并据此为B2B服务品牌的成功管理提出建议。

  8. Observation of b2 symmetry vibrational levels of the SO2 C ˜ 1B2 state: Vibrational level staggering, Coriolis interactions, and rotation-vibration constants

    Science.gov (United States)

    Park, G. Barratt; Jiang, Jun; Saladrigas, Catherine A.; Field, Robert W.

    2016-04-01

    The C ˜ 1B2 state of SO2 has a double-minimum potential in the antisymmetric stretch coordinate, such that the minimum energy geometry has nonequivalent SO bond lengths. However, low-lying levels with odd quanta of antisymmetric stretch (b2 vibrational symmetry) have not previously been observed because transitions into these levels from the zero-point level of the X ˜ state are vibronically forbidden. We use IR-UV double resonance to observe the b2 vibrational levels of the C ˜ state below 1600 cm-1 of vibrational excitation. This enables a direct characterization of the vibrational level staggering that results from the double-minimum potential. In addition, it allows us to deperturb the strong c-axis Coriolis interactions between levels of a1 and b2 vibrational symmetry and to determine accurately the vibrational dependence of the rotational constants in the distorted C ˜ electronic state.

  9. Observation of b2 symmetry vibrational levels of the SO2 C̃ (1)B2 state: Vibrational level staggering, Coriolis interactions, and rotation-vibration constants.

    Science.gov (United States)

    Park, G Barratt; Jiang, Jun; Saladrigas, Catherine A; Field, Robert W

    2016-04-14

    The C̃ (1)B2 state of SO2 has a double-minimum potential in the antisymmetric stretch coordinate, such that the minimum energy geometry has nonequivalent SO bond lengths. However, low-lying levels with odd quanta of antisymmetric stretch (b2 vibrational symmetry) have not previously been observed because transitions into these levels from the zero-point level of the X̃ state are vibronically forbidden. We use IR-UV double resonance to observe the b2 vibrational levels of the C̃ state below 1600 cm(-1) of vibrational excitation. This enables a direct characterization of the vibrational level staggering that results from the double-minimum potential. In addition, it allows us to deperturb the strong c-axis Coriolis interactions between levels of a1 and b2 vibrational symmetry and to determine accurately the vibrational dependence of the rotational constants in the distorted C̃ electronic state. PMID:27083725

  10. Growth of MgB2 Thin Films by Chemical Vapour Deposition Using B2H6 as a boron Source

    Institute of Scientific and Technical Information of China (English)

    王淑芳; 朱亚彬; 刘震; 周岳亮; 张芹; 陈正豪; 吕惠宾; 杨国桢

    2003-01-01

    Superconducting MgB2 thin films were grown on single crystal Al2O3 (0001) by chemical vapour deposition using B2H6 as a boron source. MgB2 film was then accomplished by annealing the boron precursor films in the presence of high-purity magnesium bulk at 890℃ in vacuum. The as-grown MgB2 films are smooth and c-axis-oriented.The films exhibit a zero-resistance transition of about 38K with a narrow transition width of 0.2 K. Magnetic hysteresis measurements yield the critical current density of 1.9 × 107 A/cm2 at 10 K in zero field.

  11. Synthesis and crystal structure of Cu2NiO(B2O5) and Cu2MgO(B2O5)

    International Nuclear Information System (INIS)

    A transport reaction synthesis technique has been used to prepare single crystals of two pyroborate compounds having the formulas Cu2NiO(B2O5) and Cu2MgO(B2O5). The two compounds are isostructural and crystallize in the monoclinic space group P21/c. Cu2NiO(B2O5): a=3.2003(10), b=14.775(3), c=9.097(3), β=93.28(4), V=429.4(2) A3, Z=4; and Cu2MgO(B2O5): a=3.2401(6), b=14.790(2), c=9.147(2), β=94.88(2), V=436.7(2) A3, Z=4. The structures of Cu2NiO(B2O5) and Cu2MgO(B2O5) were, respectively, refined from 804 and 1000 independent reflections to the final residuals R1=0.0366, wR2=0.0911 and R1=0.0231, wR2=0.0644. Both compounds exhibit a chevron-like structure built up of ribbons, made of edge-connected copper and nickel-oxygen polyhedra, running along the (1 0 0) direction. These ribbons are connected from one another via oxygen atoms and the cohesion of the three-dimensional network is ensured by [B2O5] entities. Cu in part occupies the position for Ni or Mg, so that the compounds actually are solid solution compounds. Ni or Mg atoms are octahedrally coordinated by oxygen, while the two pure Cu sites show [4] and [4+1] coordination, for Cu(1) and Cu(2), respectively. The ELNES B-K edge spectra for the two compounds support that the borate group present is [B2O5

  12. B2B电子商务协作模型研究%Research on B2B Electronic Business Collaboration Model

    Institute of Scientific and Technical Information of China (English)

    李双庆; 程代杰; 何玲

    2003-01-01

    B2B is an important application form in electronic business, it provides the methods to do business activities through Internet among companies. But the heterogeneous of the information systems between companies makes it difficult in interoperating between them. In this paper, a B2B electronic business collaboration model is proposed, solving the collaboration between heterogeneous business systems by defining the business irformation ontology and describing the hierarchy in business collaboration process.

  13. Analysis of practical use of modern internet technology as a mean of marketing communications in the field of B2B and B2C

    OpenAIRE

    Yu.M. Melnyk; D.V. Korinсhenko

    2015-01-01

    The aim of the article. The aim of this study is to analyze the use of modern Internet technologies as the tool of marketing communication on the example of B2B and B2C areas of companies. The main objectives are: to explore modern tools and technology of Internet communications; to identify their kinds; to analyze the main features of the Internet communications complex (tools and technologies), using selected companies; to conduct a performance evaluation of the use of Internet communica...

  14. Overlapping B2B and Family Business Marketing : A Study about Family and B2B Firms Exhibiting at Bilsport Performance and Custom Motor Show

    OpenAIRE

    Kervaire Orellana, Brian André; DeLeon, Eber Andres

    2009-01-01

    Background: Family Businesses’ way of doing marketing has similarities with B2B marketing. Usuallyfamily firms focus on what they have traditionally done well and diversify in related areas using their knowledge of how to perform in certain markets with certain customers and by offering certain productsand services. In order to do this, it is important for family firms, as for firms operating in B2Bmarkets, to create and keep good relationships with their stakeholders, so that at the end thei...

  15. Microhardness and microstructure evolution of TiB2 reinforced Inconel 625/TiB2 composite produced by selective laser melting

    Science.gov (United States)

    Zhang, Baicheng; Bi, Guijun; Nai, Sharon; Sun, Chen-nan; Wei, Jun

    2016-06-01

    In this study, micron-size TiB2 particles were utilized to reinforce Inconel 625 produced by selective laser melting. Exceptional microhardness 600-700 HV0.3 of the composite was obtained. In further investigation, the microstructure and mechanical properties of Inconel 625/TiB2 composite can be significantly influenced by addition of TiB2 particles during SLM. It was found that the long directional columnar grains observed from SLM-processed Inconel 625 were totally changed to fine dendritic matrix due to the addition of TiB2 particles. Moreover, with laser energy density (LED) of 1200 J/m, a Ti, Mo rich interface around TiB2 particles with fine thickness can be observed by FESEM and EDS. The microstructure evolution can be determined by different laser energy density (LED): under 1200 J/m, γ phase in dendrite grains; under 600 J/m, γ phase in combination of dendritic and acicular grains; under 400 J/m, γ phase acicular grains. Under optimized LED 1200 J/m, the dynamic nanohardness (8.62 GPa) and elastic modulus (167 GPa) of SLM-processed Inconel 625/TiB2 composite are higher compared with those of SLM-processed Inconel 625 (3.97 GPa and 135 GPa, respectively).

  16. MgB 2 thin films by hybrid physical-chemical vapor deposition

    Science.gov (United States)

    Xi, X. X.; Pogrebnyakov, A. V.; Xu, S. Y.; Chen, K.; Cui, Y.; Maertz, E. C.; Zhuang, C. G.; Li, Qi; Lamborn, D. R.; Redwing, J. M.; Liu, Z. K.; Soukiassian, A.; Schlom, D. G.; Weng, X. J.; Dickey, E. C.; Chen, Y. B.; Tian, W.; Pan, X. Q.; Cybart, S. A.; Dynes, R. C.

    2007-06-01

    Hybrid physical-chemical vapor deposition (HPCVD) has been the most effective technique for depositing MgB 2 thin films. It generates high magnesium vapor pressures and provides a clean environment for the growth of high purity MgB 2 films. The epitaxial pure MgB 2 films grown by HPCVD show higher-than-bulk Tc due to tensile strain in the films. The HPCVD films are the cleanest MgB 2 materials reported, allowing basic research, such as on magnetoresistance, that reveals the two-band nature of MgB 2. The carbon-alloyed HPCVD films demonstrate record-high Hc2 values promising for high magnetic field applications. The HPCVD films and multilayers have enabled the fabrication of high quality MgB 2 Josephson junctions.

  17. MgB2 thin films by hybrid physical-chemical vapor deposition

    International Nuclear Information System (INIS)

    Hybrid physical-chemical vapor deposition (HPCVD) has been the most effective technique for depositing MgB2 thin films. It generates high magnesium vapor pressures and provides a clean environment for the growth of high purity MgB2 films. The epitaxial pure MgB2 films grown by HPCVD show higher-than-bulk T c due to tensile strain in the films. The HPCVD films are the cleanest MgB2 materials reported, allowing basic research, such as on magnetoresistance, that reveals the two-band nature of MgB2. The carbon-alloyed HPCVD films demonstrate record-high H c2 values promising for high magnetic field applications. The HPCVD films and multilayers have enabled the fabrication of high quality MgB2 Josephson junctions

  18. B2B电子商务使用的研究综述

    Institute of Scientific and Technical Information of China (English)

    庞远超

    2011-01-01

    B2B电子商务是一种伴随着互联网技术发展起来的新型商务模式.本文从B2B电子商务的概念、B2B电子商务模式、企业对B2B电子商务的使用三个方面对以往研究B2B电子商务的文献进行整理和回顾。并在简要评价的基础上,并对下一步B2B电子商务的研究趋势进行了展望.

  19. erbB-2 autophosphorylation is required for mitogenic action and high-affinity substrate coupling

    DEFF Research Database (Denmark)

    Segatto, O; Lonardo, F; Helin, K;

    1992-01-01

    this EGFR/erbB-2 chimera, erbB-2 kinase activity is regulated by EGF binding. An EGFR/erbB-2 mutant bearing multiple Tyr----Phe substitutions at erbB-2 autophosphorylation sites (EGFR/erbB-2 5P) displayed markedly reduced phosphotyrosine content following EGF stimulation in comparison with the non......-mutated chimera. When expressed in NR6 cells, the EGFR/erbB-2 5P mutant was unable to deliver a sizeable mitogenic signal when activated by EGF at physiological levels. In intact cells, the 5P mutant was still able to stimulate phosphorylation of the gamma isozyme of phospholipase C (PLC-gamma), a prototype erb...

  20. Tsh receptor

    OpenAIRE

    Frauman, Albert

    2013-01-01

    The TSH receptor is a member of the G protein-coupled receptor(GPCR)family. It is one of the glycoprotein hormone receptors, which also includes the FSH and LH/CG receptors. The TSH receptor mediates the action of the pituitary-derived glycoprotein, TSH (thyroid stimulating hormone, thyrotropin or thyrotrophin). TSH binds to the TSH receptor which is located on thyroid follicular cells (but is also expressed in extrathyroidal sites). Glycosylation of the TSH receptor occurs, as does cleavage ...

  1. 聪慧地拓展B2B的空间

    Institute of Scientific and Technical Information of China (English)

    郭凡生

    2007-01-01

    信息阻滞造成的浪费,是B2B(企业间商业机会)的浪费,但也正意味着B2B商务的机会。我相信,哪儿浪费最大,哪儿就能挣到钱,所以慧聪一直在千方百计地拓展B2B。

  2. 建立真正的B2B市场

    Institute of Scientific and Technical Information of China (English)

    GlennRamsdell

    2001-01-01

    两年前,B2B市场几乎还没有出现,人们连这方面的想法也没有。如今,成千上万的人要在网上建立B2B业务,而且几乎每天都有新的B2B交易问世,其中牵涉的不乏全球性大企业。

  3. 关于电子商务B2B分析研究

    Institute of Scientific and Technical Information of China (English)

    陈昊祺

    2012-01-01

      本文结合笔者多年实践工作经验,针对电子商务B2B模式进行详细阐述,首先从B2B模式的含义以及发展现状入手,探讨了B2B各项分类以及功能体现,与大家共同探讨。

  4. Single Peak Solitons for the Boussinesq-Like B(2,2 Equation

    Directory of Open Access Journals (Sweden)

    Lina Zhang

    2013-01-01

    Full Text Available The nonlinear dispersive Boussinesq-like B(2,2 equation utt+(u2xx−(u2xxxx=0, which exhibits single peak solitons, is investigated. Peakons, cuspons and smooth soliton solutions are obtained by setting the B(2,2 equation under inhomogeneous boundary condition. Asymptotic behavior and numerical simulations are provided for these three types of single peak soliton solutions of the B(2,2 equation.

  5. Single Peak Solitons for the Boussinesq-Like B(2,2) Equation

    OpenAIRE

    Lina Zhang; Shumin Li; Aiyong Chen

    2013-01-01

    The nonlinear dispersive Boussinesq-like B(2,2) equation utt+(u2)xx−(u2)xxxx=0, which exhibits single peak solitons, is investigated. Peakons, cuspons and smooth soliton solutions are obtained by setting the B(2,2) equation under inhomogeneous boundary condition. Asymptotic behavior and numerical simulations are provided for these three types of single peak soliton solutions of the B(2,2) equation.

  6. Assay of charge of Mg in MgB2 superconductor

    International Nuclear Information System (INIS)

    XPS studies of polycrystalline MgB2 sample have shown that the charge state of Mg is less than 2(+). We have performed TB-LMTO calculation for average charge of Mg 3s orbital in MgB2 and MgF2. We found that average charge of Mg3s orbital is 0.8 in MgB2 in conformity with XPS result. (author)

  7. Trpc2-expressing sensory neurons in the mouse main olfactory epithelium of type B express the soluble guanylate cyclase Gucy1b2.

    Science.gov (United States)

    Omura, Masayo; Mombaerts, Peter

    2015-03-01

    Chemoreception in the mouse olfactory system occurs primarily at two chemosensory epithelia in the nasal cavity: the main olfactory epithelium (MOE) and the vomeronasal epithelium. The canonical chemosensory neurons in the MOE, the olfactory sensory neurons (OSNs), express the odorant receptor (OR) gene repertoire, and depend on Adcy3 and Cnga2 for chemosensory signal transduction. The canonical chemosensory neurons in the vomeronasal epithelium, the vomeronasal sensory neurons (VSNs), express two unrelated vomeronasal receptor (VR) gene repertoires, and involve Trpc2 for chemosensory signal transduction. Recently we reported the discovery of two types of neurons in the mouse MOE that express Trcp2 in addition to Cnga2. These cell types can be distinguished at the single-cell level by expression of Adcy3: positive, type A and negative, type B. Some type A cells express OR genes. Thus far there is no specific gene or marker for type B cells, hampering further analyses such as physiological recordings. Here, we show that among MOE cells, type B cells are unique in their expression of the soluble guanylate cyclase Gucy1b2. We came across Gucy1b2 in an explorative approach based on Long Serial Analysis of Gene Expression (LongSAGE) that we applied to single red-fluorescent cells isolated from whole olfactory mucosa and vomeronasal organ of mice of a novel Trcp2-IRES-taumCherry gene-targeted strain. The generation of a novel Gucy1b2-IRES-tauGFP gene-targeted strain enabled us to visualize coalescence of axons of type B cells into glomeruli in the main olfactory bulb. Our molecular and anatomical analyses define Gucy1b2 as a marker for type B cells within the MOE. The Gucy1b2-IRES-tauGFP strain will be useful for physiological, molecular, cellular, and anatomical studies of this newly described chemosensory subsystem. PMID:25701815

  8. Retargeting of natural killer-cell cytolytic activity to ErbB2-expressing cancer cells results in efficient and selective tumor cell destruction.

    Science.gov (United States)

    Uherek, Christoph; Tonn, Torsten; Uherek, Barbara; Becker, Sven; Schnierle, Barbara; Klingemann, Hans-Georg; Wels, Winfried

    2002-08-15

    The continuously growing natural killer (NK) cell line NK-92 is highly cytotoxic against malignant cells of various origins without affecting normal human cells. Based on this selectivity, the potential of NK-92 cells for adoptive therapy is currently being investigated in phase I clinical studies. To further enhance the antitumoral activity of NK-92 cells and expand the range of tumor entities suitable for NK-92-based therapies, here by transduction with a retroviral vector we have generated genetically modified NK-92 cells expressing a chimeric antigen receptor specific for the tumor-associated ErbB2 (HER2/neu) antigen, which is overexpressed by many tumors of epithelial origin. The chimeric antigen receptor consists of the ErbB2-specific scFv(FRP5) antibody fragment, a flexible hinge region derived from CD8, and transmembrane and intracellular regions of the CD3 zeta chain. Transduced NK-92-scFv(FRP5)-zeta cells express high levels of the fusion protein on the cell surface as determined by fluorescence-activated cell-scanning (FACS) analysis. In europium release assays, no difference in cytotoxic activity of NK-92 and NK-92-scFv(FRP5)-zeta cells toward ErbB2-negative targets was found. However, even at low effector-to-target ratios, NK-92-scFv(FRP5)-zeta cells specifically and efficiently lysed established and primary ErbB2-expressing tumor cells that were completely resistant to cytolytic activity of parental NK-92 cells. These results demonstrate that efficient retargeting of NK-92 cytotoxicity can be achieved and might allow the generation of potent cell-based therapeutics for the treatment of ErbB2-expressing malignancies. PMID:12149207

  9. B2C电子商务服务质量评价研究%Research on Evaluation of Service Quality for B2C E-commerce

    Institute of Scientific and Technical Information of China (English)

    施国洪; 施钟贤

    2013-01-01

    After more than ten years of development, China's network shopping has begun to enter the relative mature stage. Because the current B2C mode of the electronic commerce development is particularly rapid and its market share increase year by year, e-commerce will become the core of the future development and the focus of theoretical research. Related research shows that traditional service quality evaluation models represented by SERVQUAL model for e-commerce service quality evaluation are lack of adequate reliability, so the evaluation research for B2C e-commerce service quality has to be further deepened. This article focuses on the current research on B2C e-commerce service quality. The characteristics and existing problems in these studies are summarized and the future development direction of the B2C e-commerce service quality research is pointed out , in order to improve the service quality and provide reference and help for B2C e-commerce enterprises.%经过十余年的发展,中国的网络购物已经开始步入相对成熟的阶段,当前以B2C模式的电子商务发展尤为迅速,市场份额逐年提高,必将成为未来电子商务发展的核心及理论研究的重点。相关研究表明,以SERVQUAL模型为代表的传统服务质量评价模型对于电子商务服务质量的评价缺乏足够的信度,因此对于B2C电子商务服务质量的评价研究也就有待进一步深化。本文对当前涉及B2C电子商务服务质量的相关研究进行了重点介绍,总结了这些研究的特点以及存在的问题,指出了今后B2C电子商务服务质量的研究需要发展的方向,以期为B2C电子商务企业提高服务质量提供借鉴和帮助。

  10. Acid Leaching of SHS Produced MgO/TiB2

    OpenAIRE

    Lok, Jonathan Y.

    2006-01-01

    The stoichiometric Self-propagating High-temperature Synthesis (SHS) thermite reaction involving magnesium oxide (MgO), titanium dioxide (TiO2), and boron oxide (B2O3) forms titanium diboride (TiB2) and MgO as final products. Selective acid leaching is used to remove the MgO leaving high purity TiB2 powder. The SHS method to produce TiB2 is attractive because of the relatively low temperature required to initiate the reaction, fast reaction time, and product purity. This study investigates th...

  11. Antiaging Gene Klotho Regulates Adrenal CYP11B2 Expression and Aldosterone Synthesis.

    Science.gov (United States)

    Zhou, Xiaoli; Chen, Kai; Wang, Yongjun; Schuman, Mariano; Lei, Han; Sun, Zhongjie

    2016-06-01

    Deficiency of the antiaging gene Klotho (KL) induces renal damage and hypertension through unknown mechanisms. In this study, we assessed whether KL regulates expression of CYP11B2, a key rate-limiting enzyme in aldosterone synthesis, in adrenal glands. We found that haplodeficiency of KL(+/-) in mice increased the plasma level of aldosterone by 16 weeks of age, which coincided with spontaneous and persistent elevation of BP. Blockade of aldosterone actions by eplerenone reversed KL deficiency-induced hypertension and attenuated the kidney damage. Protein expression of CYP11B2 was upregulated in adrenal cortex of KL(+/-) mice. KL and CYP11B2 proteins colocalized in adrenal zona glomerulosa cells. Silencing of KL upregulated and overexpression of KL downregulated CYP11B2 expression in human adrenocortical cells. Notably, silencing of KL decreased expression of SF-1, a negative transcription factor of CYP11B2, but increased phosphorylation of ATF2, a positive transcription factor of CYP11B2, which may contribute to upregulation of CYP11B2 expression. Therefore, these results show that KL regulates adrenal CYP11B2 expression. KL deficiency-induced spontaneous hypertension and kidney damage may be partially attributed to the upregulation of CYP11B2 expression and aldosterone synthesis. PMID:26471128

  12. Study of preparation of TiB2 by TiC in Al melts

    International Nuclear Information System (INIS)

    TiB2 particles are prepared by TiC in Al melts and the characteristics of them are studied. It is found that TiC particles are unstable when boron exists in Al melts with high temperature and will transform to TiB2 and Al4C3. Most of the synthesized TiB2 particles are regular hexagonal prisms with submicron size. The diameter of the undersurfaces of these prisms is ranging from 200 nm to 1 μm and the height is ranging from 100 nm to 300 nm. It is considered that controlling the transformation from TiC to TiB2 is an effective method to prepare small and uniform TiB2 particles. - Highlights: ► TiC can easily transform into TiB2 in Al melts. ► TiB2 formed by TiC will grow into regular hexagonal prisms with submicron size. ► Controlling the transformation from TiC to TiB2 is an effective method to prepare small and uniform TiB2 particles.

  13. Properties of MgB2 films deposited on single crystal Ag layers

    International Nuclear Information System (INIS)

    Highlights: • MgB2 thin film can be fabricated on single crystal Ag(1 1 1) face. • As the thickness of Ag layer increases, the Tc and Jc of MgB2 decreases. When the Ag layer is 20 nm thick, the reduction of Tc is about 2 K. • Single crystal Ag layer is better than polycrystalline Ag layer in MgB2 deposition. • May enable development of MgB2 SNS junctions with single crystal Ag in the future. - Abstract: We have recently developed a method to deposit MgB2 thin films on single crystal Ag layers, and found that thin Ag layers reduced the the superconductivity of MgB2 not much, which may be a possible material to fabricate MgB2 SNS Josephson junctions. The single crystal Ag layers were deposited on (0 0 0 1) SiC substrates, and then the MgB2 thin films were deposited on the Ag layers. All the measurements included the XRD, M–T and M–H curves. The transition temperature of MgB2 films decreases from 39 K to 37 K, while the thickness of Ag layers grows from 0 to 20 nm, and the critical current density at 4.2 K decreases from 1.76 MA/cm2 to 1.24 MA/cm2, too

  14. CHARACTERIZATION OF TiB2 COATING ADHERENCE BY A MULTI-PASS SCRATCH TESTING

    OpenAIRE

    YASAR TOTIK; ERSIN ARSLAN; IHSAN EFEOGLU; IRFAN KAYMAZ

    2009-01-01

    TiB2 films deposited using various deposition techniques are used to increase the wear lifetime of industrial components. The performance of TiB2 films is dependent on the coating–substrate adhesion. In this study, the fatigue behavior of TiB2 films was investigated using the multi-mode scratch method. Films of TiB2 were deposited on silicon wafers and AISI M2 steel substrates at different frequencies by pulsed-dc closed field unbalanced magnetron sputtering (CFUBMS). The microstructures of t...

  15. Chemically vapor-deposited ZrB2 as a selective solar absorber

    International Nuclear Information System (INIS)

    Coatings of ZrB2 and TiB2 for photothermal solar absorber applications were prepared using chemical vapor deposition (CVD) techniques. Oxidation tests suggest a maximum temperature limit for air exposure of 600 K for TiB2 and 800 K for ZrB2. Both materials exhibit innate spectral selectivity with an emittance at 375 K ranging from 0.06 to 0.09, a solar absorptance for ZrB2 ranging from 0.67 to 0.77 and a solar absorptance for TiB2 ranging from 0.46 to 0.59. ZrB2 has better solar selectivity and more desirable oxidation behavior than TiB2. A 0.071 μm antireflection coating of Si3N4 deposited onto the ZrB2 coating leads to an increase in absorptance from 0.77 to 0.93, while the emittance remains unchanged. (Auth.)

  16. 关注B2B服务的发展

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

    12月7日,飞马旅参与主办的首届中国B2B服务峰会存上海举行。说起来B2B业务大家并不陌生。基本上属于公司间业务基本上都属于这个范畴。B2B服务与B2B一般业务最大的区别在哪儿呢?

  17. B2B企业市场调研的意义

    Institute of Scientific and Technical Information of China (English)

    蔺华

    2013-01-01

    什么是B2B企业?简单来讲,B2B就是企业与企业之间的各类商务活动,不与消费者直接进行的商务活动都可以归为B2B,向企业而非消费者出售产品或服务的企业称为B2B企业,

  18. B2B:登峰造极VS暮气沉沉

    Institute of Scientific and Technical Information of China (English)

    张洁; 顾卓

    2007-01-01

    @@ 说到中国的制造业就不得不说到中国的B2B,说到B2B就不得不说阿里巴巴.这个在马云带领下的B2B网站现在已成为公认的B2B老大,"打着灯笼也找不到竞争对手"的话也并非一时脑热的脱口而出.

  19. 从“雅蜂模式”谈B2B网站联盟

    Institute of Scientific and Technical Information of China (English)

    刘红梅

    2007-01-01

    在今年刚结束的首届“中国B2B联盟大会暨高峰论坛”上,中国首家全英文的国际贸易B2B垂直搜索引擎Yaphon雅蜂网正式宣告“雅蜂B2B网站联盟”成立,本文基于“雅蜂模式”探讨了B2B网站的联盟策略。

  20. Superconducting MgB2 flowers: growth mechanism and their superconducting properties

    Science.gov (United States)

    Seong, Won Kyung; Ranot, Mahipal; Lee, Ji Yeong; Yang, Cheol-Woong; Lee, Jae Hak; Oh, Young Hoon; Ahn, Jae-Pyoung; Kang, Won Nam

    2016-04-01

    We report for the first time the growth and the systematic study of the growth mechanism for flower-like MgB2 structures fabricated on the substrates for solid-state electronics by the hybrid physical-chemical vapor deposition (HPCVD) technique. The MgB2 flower has a width of 30 μm and a height of 10 μm. The superconductivity of MgB2 flowers was confirmed by a magnetization measurement, and the transition temperature is 39 K, which is comparable with high-quality bulk samples. The excellent current-carrying capability was demonstrated by MgB2 flowers. To understand the nucleation and growth mechanism of MgB2 flowers a very systematic study was performed by a high-resolution transmission electron microscope (HRTEM) and atom probe (AP) microscopy. The HRTEM revealed that the seed grain of a MgB2 flower has a [101¯0] direction, and the flower is composed of micro-columnar MgB2 grains having pyramidal tips and which are grown along the (0001) plane. A clear understanding of the growth mechanism for MgB2 flowers could lead to the growth of other low-dimensional MgB2 structures for superconducting electronic devices.

  1. Social Media Challenges for B2B Organizations : A case study of a large manufacturer

    OpenAIRE

    Berglund, Greger; Nilsson, Markus

    2011-01-01

    When looking at the engagement of social media in general we see that business-to-business (B2B) companies have a significantly lower day-to-day usage compared to business-to-consumer (B2C) companies even though there are more B2B companies present in the social media space. By studying a B2B company in the midst of implementing social media in their efforts to enhance their marketing capabilities we want to know if there are any specific reasons for these facts. When studying the company we ...

  2. XPS studies of MgB2 superconductor for charge state of Mg

    International Nuclear Information System (INIS)

    X-ray photoelectron spectroscopic (XPS) studies have been carried out on polycrystalline MgB2 pellets. Characteristic Mg-2p and B-Is spectra have been analysed for extracting binding energies. There are evidences of MgB2 and formation of traces of metallic Mg, MgO and B2O3. Binding energy of Mg in MgB2 reveals its charge state to be less than 2(+) indicative of partial and not full charge transfer from Mg to B. (author)

  3. 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.

  4. Review of magnetic features observed in (A,A')Ni2B2C solid solutions

    International Nuclear Information System (INIS)

    The nickel-borocarbides ANi2B2C [A=Y, Ln (lanthanide), An(actinide)], crystallizing in the body-centred tetragonal LuNi2B2C-type structure, are classified according to the existence or coexistence of superconducting and antiferromagnetic states (AF). The magnetic features observed in polycrystalline (A,A')Ni2B2C solid solutions, adopting the same crystal structure, are reviewed and discussed. Published data on the magnetism in (A,Ln)Ni2B2C systems (ANi2B2C nonmagnetic, A=Y,La,Lu) indicate a gradual rise in the threshold content, x(m), in (Y1-xLnx)Ni2B2C (Ln=Gd,Tb,Dy,Ho,Er) for the establishment of AF states. (A,A')Ni2B2C systems with magnetic end compounds show gradual variation in magnetic features when A and A' are both heavy Ln. The behaviour of (A,A')Ni2B2C systems of light A (Pr or U) and heavy A' (Dy or Tm) depends on the magnetic structures of the end compounds. In intermediate compositions, incomplete moment compensation in (Pr,Dy)Ni2B2C decreases TN, while different moment directions in the end compounds in (U,Dy)Ni2B2C lead to a directional frustration of ordered moments. Such a frustration in (U,Tm)Ni2B2C is related to different magnetic structures of the end compounds

  5. X-ray photoemission study of MgB2 films synthesized from in-situ annealed MgB2/Mg multilayers

    International Nuclear Information System (INIS)

    Superconducting MgB2 films were obtained by in-situ annealing of precursor multilayers deposited at low substrate temperature by sputtering from a MgB2 stoichiometric target and by thermal evaporation of pure Mg. After an in-situ annealing at 500-600 C, the films showed a zero resistance critical temperature up to 31 K. The as-obtained MgB2 films were investigated by X-ray photoelectron spectroscopy (XPS) and X-ray Auger electron spectroscopy (XAES). The electronic structure was studied by monitoring the B 1s, Mg 2p, O 1s core-levels and the Mg KL2L3 Auger line. For comparison, the electronic structure of an MgB2 commercial superconducting sputtering target, of a not-annealed precursor film and of a sample obtained by direct sputtering from the MgB2 target have also been investigated. Electron spectroscopy showed that in the superconducting systems the Mg KL2L3 Auger line kinetic energy position is always higher by about 0.9 eV with respect to the energy position of the same Auger line measured in the non-superconducting samples. (orig.)

  6. Cyclin B2 and p53 control proper timing of centrosome separation

    NARCIS (Netherlands)

    Nam, H.J.; Deursen, J.M.A. van

    2014-01-01

    Cyclins B1 and B2 are frequently elevated in human cancers and are associated with tumour aggressiveness and poor clinical outcome; however, whether and how B-type cyclins drive tumorigenesis is unknown. Here we show that cyclin B1 and B2 transgenic mice are highly prone to tumours, including tumour

  7. Occurrence of Furnonisins B2 and B4 in Retail Raisins

    DEFF Research Database (Denmark)

    Knudsen, Peter Boldsen; Mogensen, Jesper Mølgaard; Larsen, Thomas Ostenfeld;

    2011-01-01

    -MS/MS survey of fumonisins in retail raisins. In 10 of 21 brands collected in Denmark, Germany, and The Netherlands, fumonisins B-2 and B-4 were detected at levels up to 13 and 1.3 mu g/kg, respectively. Only fumonisin B-2 has been detected in wine, so the presence of fumonisin B-4 in raisins suggests that the...

  8. Ambient temperature cured TiB2 cathode coating for aluminum electrolysis

    Institute of Scientific and Technical Information of China (English)

    赖延清; 李庆余; 杨建红; 李劼

    2003-01-01

    The concept of ambient temperature curable TiB2 cathode coating was put forward, and the ambient temperature curable TiB2 cathode coating was prepared successfully. Differing from the previous TiB2 cathode coating solidified approximately at 200 ℃,the ambient temperature curable TiB2 cathode coating can be solidified at room temperature, so the heating equipment is not necessary, which simplifies the preparation process and facilitates the industrial application of TiB2 cathode coating. Many kinds of resin and curing agent were investigated. On the above-mentioned basis, the ambient temperature curable TiB2 cathode coating was prepared with furan resin 5 500 mixed with complex resins B as carbon binder and DXG1 as curing agent in 24 h. The results show that the properties of prepared coating are excellent, the electrical resistivity is 29.8 μΩ*m, the compressive strength is 33.6 MPa, which are all better than the relevant properties of partially graphitized cathode carbon block for aluminum electrolysis prescribed by the GB 8744-88. SEM morphologies show that the section morphology of the TiB2 coating is unaltered during the electrolysis test, the TiB2 coating can be used in aluminum electrolysis industry to save energy and prolong the life of aluminum electrolysis cell.

  9. Antibacterial Peptide CecropinB2 Production via Various Host and Construct Systems

    Directory of Open Access Journals (Sweden)

    Wei-Shiang Lai

    2016-01-01

    Full Text Available Cecropin is a cationic antibacterial peptide composed of 35–39 residues. This peptide has been identified as possessing strong antibacterial activity and low toxicity against eukaryotic cells, and it has been claimed that some types of the cecropin family of peptides are capable of killing cancer cells. In this study, the host effect of cloning antibacterial peptide cecropinB2 was investigated. Three different host expression systems were chosen, i.e., Escherichia coli, Bacillus subtilis and Pichia pastoris. Two gene constructs, cecropinB2 (cecB2 and intein-cecropinB2 (INT-cecB2, were applied. Signal peptide and propeptide from Armigeres subalbatus were also attached to the gene construct. The results showed that the best host for cloning cecropinB2 was P. pastoris SMD1168 harboring the gene of pGAPzαC-prepro-cecB2 via Western blot confirmation. The cecropinB2 that was purified using immobilized-metal affinity chromatography resin showed strong antibacterial activity against the Gram-negative strains, including the multi-drug-resistant bacteria Acinetobacter baumannii.

  10. Pair-Breaking Critical Current Density of Two-Band Superconductor MgB2

    Institute of Scientific and Technical Information of China (English)

    I.N. Askerzade

    2005-01-01

    Temperature dependence of the pair-breaking critical current density of MgB2, jd(T), is studied using a two-band Ginzburg-Landau theory. The results are shown to be in good agreement with experimental data for the superconducting magnesium diboride MgB2.

  11. Conceptualizing B2C Businesses as a New Category of Services

    OpenAIRE

    Anil Pandya; Nikhilesh Dholakia

    2005-01-01

    Conceptualizing B2C businesses as an innovative class of technology-infused services yields insights into the factors that may lead to success or failure of such businesses. Drawing from services’ marketing literature and recent thinking on Internet service metrics, this paper presents a framework for analyzing B2C businesses.

  12. Effects of Hf doping on magnetic properties of MgB2 superconductor

    International Nuclear Information System (INIS)

    Magnetisation and upper critical field measurements of hafnium doped MgB2 are presented. There is an increase in upper critical field and enhancement of critical current density in hafnium doped MgB2. The irreversibility line extracted from Jc shows an upward shift. The enhancement has been more than that by neon ion irradiation. (author)

  13. Formation of MgB2 at ambient temperature with an electrochemical process: a plausible mechanism

    International Nuclear Information System (INIS)

    The binary intermetallic MgB2 superconductor has been synthesized by many research groups. However, the mechanism of its formation is not clearly understood. In this communication, a comprehensive mechanism of the formation of MgB2 from Le Chatelier's principle of equilibrium reaction has been explained both for solid-state reaction and electrodeposition methods. (rapid communication)

  14. 17 CFR 270.24b-2 - Filing copies of sales literature.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Filing copies of sales literature. 270.24b-2 Section 270.24b-2 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION... literature. Copies of material filed with the Commission for the sole purpose of complying with section...

  15. 26 CFR 31.3406(b)(2)-3 - Window transactions.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Window transactions. 31.3406(b)(2)-3 Section 31... SOURCE Collection of Income Tax at Source § 31.3406(b)(2)-3 Window transactions. (a) Requirement to backup withhold. Withholding under section 3406 applies to a window transaction (as defined in...

  16. Role of ErbB family receptor tyrosine kinases in intrahepatic cholangiocarcinoma

    OpenAIRE

    Sirica, Alphonse E.

    2008-01-01

    Aberrant expression and signaling of epidermal growth factor receptor (ErbB) family receptor tyrosine kinases, most notably that of ErbB2 and ErbB1, have been implicated in the molecular pathogenesis of intrahepatic cholangiocarcinoma. Constitutive overexpression of ErbB2 and/or ErbB1 in malignant cholangiocytes has raised interest in the possibility that agents which selectively target these receptors could potentially be effective in cholangiocarcinoma therapy. However, current experience w...

  17. MgB2 multifilamentary tapes: microstructure, chemical composition and superconducting properties

    Science.gov (United States)

    Birajdar, B.; Braccini, V.; Tumino, A.; Wenzel, T.; Eibl, O.; Grasso, G.

    2006-09-01

    Multifilamentary Ni-sheathed Cu-stabilized MgB2 tapes with a critical current density of 2.0 × 105 A cm-2 (at 20 K and 1 T) were prepared by a powder in tube technique, using pre-reacted MgB2 powders. The microstructure and chemical composition of the superconducting core and the MgB2-Ni interface were studied using SEM, EPMA and TEM. A quick, reliable and standard-less method of B quantification using SEM-EDX is established for the analysis of MgB2 wires and tapes. Carbon-contamination-free sample preparation was crucial for the analysis of boron. The typical size of MgB2 colonies, i.e. the arrangement of several well connected grains, in the MgB2 filaments was between 1 and 6 µm. The colonies are structurally well connected to each other, although sub-micrometre-sized voids are present. The B to Mg mole fraction ratio in the MgB2 colonies was found to be close to two and the O mole fraction is less than 1 at.%. The typical size of the MgB2 grains in the colonies is about 0.5-1 µm however, numerous grains of size 30-200 nm are also present. MgO precipitates of the size of 15-70 nm were found in the MgB2 grains. Long straight dislocations with a density of 1 × 1010 cm-2 are observed. Non-superconducting layers which appear as oxide layers in SEM and TEM samples were found on the surface of the MgB2 colonies and yield poor connectivity between the colonies. It is expected that these layers yield a significant reduction of the critical current density Jc. A 10 µm wide intermetallic reaction layer of B, Mg and Ni is formed at the MgB2-Ni interface. Reduction of the MgB2 grain size by milling of starting MgB2 powder and elimination of non-superconducting layers around MgB2 colonies could further enhance the critical current density because of improved pinning and connectivity between colonies.

  18. Analysis of characteristics associated with reinjection of icatibant

    DEFF Research Database (Denmark)

    Longhurst, Hilary J; Aberer, Werner; Bouillet, Laurence; Caballero, Teresa; Fabien, Vincent; Zanichelli, Andrea; Maurer, Marcus; Bygum, Anette

    2015-01-01

    PURPOSE: Phase 3 icatibant trials showed that most hereditary angioedema (HAE) (C1 inhibitor deficiency) acute attacks were treated successfully with one injection of icatibant, a selective bradykinin B2 receptor antagonist. We conducted a post hoc analysis of icatibant reinjection for HAE type I...

  19. Mechanical Properties and Microstructure of In Situ TiB2-7055 Composites

    Institute of Scientific and Technical Information of China (English)

    CHEN dong; LE Yong-kang; BAI Liang; MA Nai-heng; LI Xian-feng; WANG Hao-wei

    2006-01-01

    In order to fabricate a kind of high strength particulate reinforced aluminum-matrix composites, the high strength aluminum alloy 7055 was selected as a matrix. Composites reinforced with varying amounts of TiB2 particles were synthesized using the in situ method, and their mechanical properties and microstructure were analyzed. It is found that the in situ TiB2 particles sized from 50 to 400 nm uniformly disperse in the matrix. With the weight fraction of TiB2 particles increasing, the elastic modulus as well as the yield strength and the ultimate tensile strength increase, while the ductility decrease. The improvement of strength could be attributed to good bonding between TiB2 and the matrix, and also the TiB2 particles act as a barrier to dislocation.

  20. Possible coexistence of superconductivity and magnetic order in NdPt2B2C

    Indian Academy of Sciences (India)

    S K Dhar; A D Chinchure; E Alleno; C Godart; L C Gupta; R Nagarajan

    2002-05-01

    Coexistence of superconductivity and magnetic order has been one of the exciting aspects of the quaternary borocarbide superconductors. So far, RNi2B2C (R=Tm, Er, Ho and Dy) are the only known magnetic superconductors in this family. Here, we present our resistivity, magnetization and heat capacity studies on NdPt2B2C (nominal composition, NdPt1.5Au0.6B2C and NdPt2.1B2.4C1.2). We find superconductivity in both samples with c,onset∼ 3 K. Bulk magnetic order is found to occur below 1.7 K. We suggest that NdPt2B2C is a possible magnetic superconductor.

  1. C-erbB-2 expression and benefit from adjuvant chemotherapy and radiotherapy of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Staal, O.; Sullivan, S.; Wingren, S.; Skoog, L.; Rutqvist, L.E.; Nordenskjoeld, B. [Karolinska Sjukhuset, Stockholm (Sweden); Carstensen, J.M. [Linkoeping Univ. (Sweden)

    1995-12-31

    Frozen tissue from primary tumours of 152 premenopausal breast cancer patients, who participated in a trial comparing radiotherapy with adjuvant chemotherapy (cyclophosphamide, methotrexate, 5-fluorouracil, CMF), was analysed for c-erbB-2 protein expression, measured by flow cytometry. The relative risk of distant recurrence or death in the chemotherapy group as compared with the radiotherapy group was 3.0 (95% confidence interval (CI) 1.1-7.8) for patients whose tumours showed high c-erbB-2 levels and 0.87 (95% CI 0.43-1.7) for those with tumours with low levels of c-erbB-2 protein. Patients with highly proliferative tumours that did not overexpress c-erbB-2 benefited most, in terms of survival, from CMF. In addition, we found an increased risk of locoregional recurrence for tumours overexpressing c-erbB-2 when radiotherapy was replaced by chemotherapy. (author).

  2. Phase formation in the BaB2O4-BaF2 system

    Science.gov (United States)

    Bekker, T. B.; Fedorov, P. P.; Kokh, A. E.

    2012-07-01

    It is shown that the BaB2O4-BaF2 system is quasi-binary with the following eutectics coordinates: 760°C, 59 mol % BaF2, 41 mol % BaB2O4. Due to the intense pyrohydrolysis during the growth of β-BaB2O4 crystals from the 55.6 mol % BaB2O4-44.4 mol % BaF2 composition, the Ba5B4O11 compound is formed in the system. This process leads to the cocrystallization of the β-BaB2O4 and Ba5B4O11 phases and impedes the formation of high-quality crystals.

  3. Electroless deposition of superconducting MgB2 films on various substrates

    International Nuclear Information System (INIS)

    The superconducting properties of magnesium diboride (MgB2) films prepared by electroless deposition on various substrates including silver, gold and silicon are reported. In this study, MgB2 films were fabricated on silver, gold, and silicon using an electroless plating technique, while controlling the redox potential to improve the deposition quality. The structure, morphology, and superconducting properties of the samples were investigated using X-ray diffraction, magnetometry, scanning electron microscopy, and Raman spectroscopy. X-ray diffraction and Raman spectroscopy confirmed that the films are polycrystalline MgB2 but also contain some impurity phases. All the MgB2 films show superconducting transitions near 39 K, the value for bulk MgB2, with the superconducting volume fraction ranging from approximately 1 to 2%. We find a strong dependence of film quality with the oxidation potential of the bath.

  4. Consolidation of B4C-TaB2 eutectic composites by spark plasma sintering

    OpenAIRE

    Dmytro Demirskyi

    2015-01-01

    The in situ synthesis/consolidation of B4C-TaB2 eutectic composites by spark plasma sintering (SPS) is reported. The microstructure–property relations were determined for composites with the B4C-TaB2 eutectic composition as functions of TaB2 content, and TaB2-TaB2 interlamellar spacing. A clear maximum in fracture toughness was identified (∼4.5 MPa m1/2) for eutectic composites with interlamellar spacing between 0.9 and 1.1 μm. The composites with the hypereutectic composition of 40 mol.% TaB...

  5. Composite Cu/Fe/MgB2 superconducting wires and MgB2/YSZ/Hastelloy coated conductors for ac and dc applications

    International Nuclear Information System (INIS)

    We discuss the results of a study of MgB2 multifilamentary conductors and coated conductors from the point of view of their future dc and ac applications. The correlation between the slope of the irreversibility line induced by neutron irradiation defects and in situ structural imperfections and the critical temperature and critical current density is discussed with respect to the conductor performance and applicability. We debate the possible origin of the observed anomalous decrease of ac susceptibility at 50 K in copper clad in situ powder-in-tube MgB2 wires. Different conductor preparation methods and conductor architectures, and attainable critical current densities are presented. Some numerical results on critical currents, thermal stability and ac losses of future MgB2 multifilamentary and coated conductors with magnetic cladding of their filaments are also discussed

  6. Hall effect in LuNi2B2C and YNi2B2C borocarbides in normal and superconducting mixed states

    International Nuclear Information System (INIS)

    It was shown that the Hall resistivity ρxy for LuNi2B2C and YNi2B2C is negative in the normal and mixed states and has no sign reversal below Tc. In the mixed state the scaling relation ρxy approximately ρxxβ (ρxx is the longitudinal resistivity) was found for both compounds with β ∼ 2.0. In the normal state a distinct nonlinearity in the ρxy(H) dependence, accompanied by a large magnetoresistance, was found below 40 K only for LuNi2B2C. The difference in the behavior of Lu- and Y-based borocarbides seems to be connected with the difference in the Fermi surfaces of these compounds

  7. The NbB2-phase revisited: Homogeneity range, defect structure, superconductivity

    International Nuclear Information System (INIS)

    The discovery of superconductivity below 40 K in MgB2 has motivated new investigations on similar compounds, especially on binary diborides. The great majority of these compounds represent the AlB2-type structure (P6/mmm space group, number 191) and comprise line compounds. However, among those, NbB2 and TaB2 are reported to present a significant homogeneity region, a value of 12 at.% being reported for the case of NbB2. In this work we have evaluated the homogeneity range of the NbB2-phase through detailed microstructural characterization of as-cast, as-cast + heat-treated and solid state sintered Nb-B alloys. Neutron diffraction experiments were performed to assess the defect mechanism responsible for accommodating the non-ideal NbB2 stoichiometries (ideal = 66.7 at.% B). The results clearly showed that the width of the homogeneity range of this phase is nearly 5 at.%, extending from 65 at.% B (NbB1.86) up to 70 at.% B (NbB2.34). Rietveld refinement of the neutron intensity diffraction data indicated a random distribution of vacancies in the Nb-subnet for hyperstoichiometric NbB2. The occurrence of a possible Nb-vacancy ordered supercell was evaluated; however, a simple AlB2-type is observed throughout the entire homogeneity range. The superconducting properties of selected alloys were checked via magnetic measurements. The Nb-deficient samples were found to contain traces of a superconducting phase with T c ∼ 3.5 K

  8. Scorpion (Buthus tamulus venom toxicity on cardiopulmonary reflexes involves kinins via 5-HT3 receptor subtypes

    Directory of Open Access Journals (Sweden)

    S. BAGCHI

    2001-01-01

    Full Text Available The mechanisms underlying the action of Indian red scorpion Buthus tamulus (BT venom-induced augmentation of cardiopulmonary reflexes elicited by intravenous injection of 5-HT were examined in urethane anaesthetized rats. The 5-HT produced a concentration-dependent increase in time-response area of bradycardiac response, with the responses at submaximal concentrations shifted to the left after exposure to BT venom (20 µg/kg, IV. Aprotinin (6000 kallikrein inactivating unit, IV as such had no effect on 5-HT reflex responses (bradycardia, hypotension, and apnea, but blocked the venom-induced reflex augmentation. While ondansetron (10 µg/kg, IV completely blocked the 5-HT reflex responses, these reappeared partially after venom exposure (20 µg/kg. Exposure to bradykinin (50 µg/kg, IV for 30 min also augmented the 5-HT-induced reflex responses similar to venom. The bradykinin-induced augmentation was also blocked by ondansetron. Results indicate that the venom-induced augmentation of cardiopulmonary reflexes is mediated through kinins sensitizing 5-HT3 receptor subtypes.

  9. Modulación en la expresión de biomarcadores (RE, RP y C-erbB2 en cáncer de mama tras tratamiento neoadyuvante Modulation of biomarkers expression (OR, PR and C-erbB2 in breast cancer following neoadjuvant treatment

    Directory of Open Access Journals (Sweden)

    A. Córdoba

    2006-12-01

    Full Text Available Introducción: El tratamiento oncológico pre y postoperatorio en pacientes con carcinoma de mama está condicionado entre otros factores, por el resultado del estudio inmunohistoquímico de los receptores hormonales y por la expresión de c-erbB2. El objetivo del estudio es determinar la influencia del tratamiento neoadyuvante en la expresión de receptores de estrógeno (RE, progesterona (PR y c-erbB2. Material y métodos. Estudiamos 53 pacientes con cáncer de mama diagnosticadas mediante biopsia "trucut". Las pacientes con carcinoma localmente avanzado (20 se someten a quimioterapia preoperatoria. Se realiza extirpación quirúrgica en todos los casos. Comparamos la expresión de receptores de estrógeno (RE, receptores de progesterona (PR y c-erbB2, en la biopsia"trucut" y en la pieza quirúrgica. Resultados. Encontramos diferencias significativas en la expresión de RE, RP entre biopsia/pieza quirúrgica, comparando el grupo de pacientes sometidas a tratamiento neoadyuvante frente al grupo de pacientes sin tratamiento oncológico prequirúrgico. Encontramos diferencias de signo (positivización y negativización entre un 10 y un 40% de casos en la expresión inmunohistoquímica para RE, RP y c-erbB2 entre la biopsia"trucut" y la resección quirúrgica en las pacientes tratadas con neoadyuvancia. Estas diferencias de signo no tienen significación estadística.Introducción: Pre and post-operative oncological therapy in patients with breast cancer is determined, amongst other factors, by hormone receptor status and by c-erbB2 expression. The aim of this study is to determine the influence of neoadjuvant therapy on the expression of oestrogen receptor (OR, progesterone receptor (PR and c-erbB2. Methods. Fifty-three patients with breast cancer diagnosed by tru-cut biopsy were studied. Patients with locally advanced carcinoma (20 had preoperative treatment. All patients underwent surgical resection. Expression of OR, PR and c-erbB2 in both the

  10. Ab-initio investigation of the covalent bond energies in the metallic covalent superconductor MgB2 and in AlB2

    OpenAIRE

    Bester, Gabriel; Fahnle, Manfred

    2001-01-01

    The contributions of the covalent bond energies of various atom pairs to the cohesive energy of MgB2 and AlB2 are analysed with a variant of our recently developed energy-partitioning scheme for the density-functional total energy. The covalent bond energies are strongest for the intralayer B-B pairs. In contrast to the general belief, there is also a considerable covalent bonding between the layers, mediated by the metal atom. The bond energies between the various atom pairs are analysed in ...

  11. Social Media within a B2B context : A qualitative study about how industrial corporations can use social media to maintain B2B relationships

    OpenAIRE

    Andersén, Sophia; Bengtsson, Annie; Gilén, Sandra

    2014-01-01

    The last thirty years there has been a dramatic change in relationship marketing. The use of computers connected to the Internet at work places has increased over time and social media is widely used in marketing strategies. Social media is a new phenomenon to communicate with each other, it enables market information based on individual consumer’s experiences. Therefore managers are seeking a way to incorporate social media into their strategies, but this is more common within B2C than B2B. ...

  12. Some SEO Skills for Foreign Trade Enterprise' s B2C Website%实用外贸B2C网站SEO优化技巧

    Institute of Scientific and Technical Information of China (English)

    刘庆华

    2012-01-01

    B2C网站是未来外贸企业开展业务的一个方向,而SEO优化是企业B2C网站能否运营成功的基础.列举了一些SEO优化的实用技巧,主要包括:如何选择域名、如何设计网站框架、网站内容如何设计、网站搜索功能如何优化以及如何添加网站的外部链接等.

  13. A B2 SINE insertion in the Comt1 gene (Comt1 B2i ) results in an overexpressing, behavior modifying allele present in classical inbred mouse strains

    OpenAIRE

    Kember, R L; Fernandes, C.; Tunbridge, E.M.; Liu, L; Payá-Cano, J L; M. J. Parsons; Schalkwyk, L.C.

    2010-01-01

    Catechol-O-methyltransferase (COMT) is a key enzyme for dopamine catabolism and COMT is a candidate gene for human psychiatric disorders. In mouse it is located on chromosome 16 in a large genomic region of extremely low variation among the classical inbred strains, with no confirmed single nucleotide polymorphisms (SNPs) between strains C57BL/6J and DBA/2J within a 600-kB window. We found a B2 SINE in the 3′ untranslated region (UTR) of Comt1 which is present in C57BL/6J (Comt1 B2i ) and oth...

  14. Functional expression of a single-chain antibody to ErbB-2 in plants and cell-free systems

    Directory of Open Access Journals (Sweden)

    Benevolo Maria

    2006-09-01

    Full Text Available Abstract Background Aberrant signaling by ErbB-2 (HER 2, Neu, a member of the human Epidermal Growth Factor (EGF receptor family, is associated with an aggressive clinical behaviour of carcinomas, particularly breast tumors. Antibodies targeting the ErbB-2 pathway are a preferred therapeutic option for patients with advanced breast cancer, but a worldwide deficit in the manufacturing capacities of mammalian cell bioreactors is foreseen. Methods Herein, we describe a multi-platform approach for the production of recombinant Single chain Fragments of antibody variable regions (ScFvs to ErbB-2 that involves their functional expression in (a bacteria, (b transient as well as stable transgenic tobacco plants, and (c a newly developed cell-free transcription-translation system. Results An ScFv (ScFv800E6 was selected by cloning immunoglobulin sequences from murine hybridomas, and was expressed and fully functional in all the expression platforms, thereby representing the first ScFv to ErbB-2 produced in hosts other than bacteria and yeast. ScFv800E6 was optimized with respect to redox synthesis conditions. Different tags were introduced flanking the ScFv800E6 backbone, with and without spacer arms, including a novel Strep II tag that outperforms conventional streptavidin-based detection systems. ScFv800E6 was resistant to standard chemical radiolabeling procedures (i.e. Chloramine T, displayed a binding ability extremely similar to that of the parental monovalent Fab' fragment, as well as a flow cytometry performance and an equilibrium binding affinity (Ka approximately 2 × 108 M-1 only slightly lower than those of the parental bivalent antibody, suggesting that its binding site is conserved as compared to that of the parental antibody molecule. ScFv800E6 was found to be compatible with routine reagents for immunohistochemical staining. Conclusion ScFv800E6 is a useful reagent for in vitro biochemical and immunodiagnostic applications in oncology

  15. Adoption of the B2SAFE EUDAT replication service by the EPOS community

    Science.gov (United States)

    Cacciari, Claudio; Fares, Massimo; Fiameni, Giuseppe; Michelini, Alberto; Danecek, Peter; Wittenburg, Peter

    2014-05-01

    B2SAFE is the EUDAT service for moving and replicating data between sites and storage systems for different purposes. The goal of B2SAFE is to keep the data from a repository safe by replicating it across different geographical and administrative zones according to a set of well-defined policies. It is also a way to store large volumes of data permanently at those sites which are providing powerful on-demand data analysis facilities. In particular, B2SAFE operates on the domain of registered data where data objects are referable via persistent identifiers (PIDs). B2SAFE is more than just copying data because the PIDs must be carefully managed when data objects are moved or replicated. The EUDAT B2SAFE Service offers functionality to replicate datasets across different data centres in a safe and efficient way while maintaining all information required to easily find and query information about the replica locations. The information about the replica locations and other important information is stored in PID records, each managed in separate administrative domains. The B2SAFE Service is implemented as an iRODS module providing a set of iRODS rules or policies to interface with the EPIC handle API and uses the iRODS middleware to replicate datasets from a source data (or community) centre to a destination data centre. The definition of the dataset(s) to replicate is flexible and up to the communities using the B2SAFE service. While the B2SAFE is internally using the EPIC handle API, communities have the choice to use any PID system they prefer to assign PIDs to their digital objects. A reference to one or more EUDAT B2SAFE PIDs is returned by the B2SAFE service when a dataset is replicated. The presentation will introduce the problem space of B2SAFE, presents the achievements that have been made during the last year for enabling communities to make use of the B2SAFE service, demonstrates a EPOS use cases, outlines the commonalities and differences between the policies

  16. Endocytic down-regulation of ErbB2 is stimulated by cleavage of its C-terminus

    DEFF Research Database (Denmark)

    Lerdrup, Mads; Bruun, Silas; Grandal, Michael Vibo;

    2007-01-01

    protein (CFP) to the N- and C-terminus of ErbB2, respectively (YFP-ErbB2-CFP). After geldanamycin stimulation YFP-ErbB2-CFP became cleaved in nonapoptotic cells in a proteasome-dependent manner, and a markedly larger relative amount of cleaved YFP-ErbB2-CFP was observed in early endosomes than in the...

  17. Signatures of spin-glass behaviour in PrIr2B2 and heavy fermion behaviour in PrIr2B2C.

    Science.gov (United States)

    Anupam; Anand, V K; Hossain, Z; Adroja, D T; Geibel, C

    2011-09-21

    The magnetic and transport properties of PrIr(2)B(2) and PrIr(2)B(2)C have been investigated by dc and ac magnetic susceptibility, specific heat, electrical resistivity and magnetoresistance measurements. PrIr(2)B(2) forms in CaRh(2)B(2)-type orthorhombic crystal structure (space group Fddd). At low fields the dc magnetic susceptibility of PrIr(2)B(2) exhibits a sharp anomaly near 46 K which is followed by an abrupt increase below 10 K with a peak at 6 K, and split-up in ZFC and FC data below 46 K. In contrast, the specific heat exhibits only a broad Schottky type hump near 9 K which indicates that there is no long range magnetic order in this compound. The thermo-remanent magnetization is found to decay very slowly with a mean relaxation time τ = 3917 s. An ac magnetic susceptibility measurement also observes two sharp anomalies; the peak positions strongly depend on the frequency and shift towards high temperature with an increase in frequency, obeying the Vogel-Fulcher law as expected for a canonical spin-glass system. The two spin-glass transitions occur at freezing temperatures T(f1) = 36 K and T(f2) = 3.5 K with shifts in the freezing temperatures per decade of frequency δT(f1) = 0.044 and δT(f2) = 0.09. An analysis of the frequency dependence of the transition temperature with critical slowing down, τ(max)/τ(0) = [(T(f)-T(SG))/T(SG)](-zν), gives τ(0) = 10(-7) s and exponent zν = 8, and the Vogel-Fulcher law gives an activation energy of 84 K for T(f1) and 27.5 K for T(f2). While zν = 8 is typical for spin-glass system, the characteristic relaxation time τ(0) = 10(-7) s is very large and comparable to that of superspin-glass systems. An addition of C in PrIr(2)B(2) leads to PrIr(2)B(2)C which forms in LuNi(2)B(2)C-type tetragonal structure (space group I4/mmm) and remains paramagnetic down to 2 K. The specific heat data show a broad Schottky type anomaly, which could be fairly reproduced with CEF analysis which suggests that the ground state is a

  18. Expression of p53, Ki-67 and c-erb B2 in growth hormone-and/or prolactin-secreting pituitary adenomas Expressão de p53, Ki-67 e c-erb B2 em adenomas hipofisários secretores de prolactina e/ou hormônio de crescimento

    Directory of Open Access Journals (Sweden)

    Carlos Henrique A. Botelho

    2006-03-01

    Full Text Available The subcellular events implicated on the formation and behavior of pituitary adenomas are not fully understood. In this study we investigated the presence of p53, Ki-67 and c-erb B2 in 38 pituitary adenomas with immunohistochemical positivity for GH and prolactin (n=26; 68.4%, for prolactin (n=9; 23.7% and for GH (n=3. 7.8%. The analyses revealed the following results: 24 (63.2% tumors expressed variable positivity for c-erb B2, 11 (28.9% expressed p53 positivity and 11 (28.9% tumors were variably positive for Ki-67. Our results demonstrated a high percentage of GH/prolactin-, prolactin- and GH-secreting tumors with immunohistochemical positivity for c-erb B2. Once this membrane receptor is related to growth factors EGF and TGFalpha and both have a definite effect on tumor growth, our data suggest a possible role for c-erb B2 on the evolution of these tumors.Os eventos subcelulares implicados na formação e comportamento dos adenomas hipofisários não são completamente compreendidos. Neste estudo nós investigamos a presença de p53, Ki-67 e c-erb B2 em 38 adenomas hipofisários com positividade imuno-histoquímica para GH e prolactina (n=26, 68,4%, para prolactina (n=9, 23,7% e para GH (n=3, 7,8%. A análise revelou os seguintes resultados: 24 tumores (63,2% expressaram positividade variável para c-erb B2, 11 (28,9% expressaram positividade para p53 e 11 tumores (28,9% foram variavelmente positivos para Ki-67. Nossos resultados demonstraram elevada percentagem de tumores secretores de GH/prolactina, prolactina e GH com positividade imuno-histoquímica para c-erb B2. Desde que este receptor de membrana está relacionado aos fatores de crescimento EGF e TGFalfa e ambos têm efeito definido no crescimento tumoral, nossos dados sugerem possível função para o c-erb B2 na evolução destes tumores.

  19. EXPRESSION AND SIGNIFICANCE OF C-erbB-2 IN THE TISSUES OF LUNG CANCER

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To elucidate the expression and clinical significance of C-erbB-2 in the tissue of lung cancer. Methods Immunohistochemistry method was used to detect the protein expression of C-erbB-2 in lung cancer tissue. Results The positive expression rate of C-erbB-2 protein in 38 cases of lung cancer was 53.3% (21/38),which was higher than those in lung benign control group (P<0. 001). The significant correlation were found between the protein level and tumor stage(r= +0. 64,P<0.02). The order was stage Ⅳ>stage Ⅲ >stage Ⅱ >stage Ⅰ . There was no correlation among protein expression of C-erbB-2 in various histological types of lung cancer (P>0.05 for all). Conclusion The positive expression rates of C-erbB-2 were significantly higher in lung cancer group than those in benign control group. There is significant correlation between C-erbB-2 expression and lung cancer stage. There is no correlation among protein expression of C-erbB-2 and histological types of lung cancer.

  20. Seizure suppression by shakB2, a gap junction mutation in Drosophila.

    Science.gov (United States)

    Song, Juan; Tanouye, Mark A

    2006-02-01

    Gap junction proteins mediate electrical synaptic transmission. In Drosophila, flies carrying null mutations in the shakB locus, such as shakB2, have behavioral and electrophysiological defects in the giant fiber (GF) system neurocircuit consistent with a loss of transmission at electrical synapses. The shakB2 mutation also affects seizure susceptibility. Mutant flies are especially seizure-resistant and have a high threshold to evoked seizures. In addition, in some double mutant combinations with "epilepsy" mutations, shakB2 appears to act as a seizure-suppressor mutation: shakB2 restores seizure susceptibility to the wild-type range in the double mutant. In double mutant combinations, shakB2 completely suppresses seizures caused by slamdance (sda), knockdown (kdn), and jitterbug (jbug) mutations. Seizures caused by easily shocked (eas) and technical knockout (tko) mutations are partially suppressed by shakB2. Seizures caused by bang-sensitive (bas2) and bang-senseless (bss1, bss2 alleles) mutations are not suppressed by shakB2. These results show the use of Drosophila as a model system for studying the kinds of genetic interactions responsible for seizure susceptibility, bringing us closer to unraveling the complexity of seizure disorders in humans. PMID:16192342

  1. Microstructure and mechanical properties of novel ZrB2-reinforced zirconium alloys

    International Nuclear Information System (INIS)

    Novel ZrB2-reinforced zirconium (Zr) alloys with different boron (B) and aluminum (Al) contents were produced by arc-melting technique. Microstructural observation indicated that both the α-lath and the prior-β grain size were significantly refined with increased B content. The thickness of α lath gradually increased with increased solute atom Al content. Compressive test results showed that the modulus and strengths of the alloys improved with increased ZrB2 and Al contents. The presence of abundant ZrB2 whiskers and solid solution atom Al were responsible for the increased Young's modulus. The strengthening mechanisms can be attributed to strengthening through load transfer between the ZrB2 whiskers and Zr matrix, morphological changes in alloys resulting from the formation of ZrB2 whiskers, and solid-solution strengthening caused by Al addition. Fractography confirmed that ZrB2 whiskers undertook the load transferred from Zr matrix and that crack sources were primarily generated at ZrB2 whiskers

  2. 中国B2B电子商务模式体验

    Institute of Scientific and Technical Information of China (English)

    胡伟

    2012-01-01

    B2B(Business-to-Business)电子商务是指企业与企业之间通过互联网进行产品、服务及信息交换的电子商务活动,它是当前电子商务模式中历史最长、发展最完善、份额最大、最具操作性、最易成功的模式,目前主要包括垂直B2B、水平B2B、自建B2B、关联行业B2B四种模式.笔者以中国供求网(www.gongqiu.com.cn)为引,从B2B电子商务网站建设、业务模式、增值服务(主要是搜索引擎优化)、人才建设等方面分享了对国内B2B电子商务的体会和见解.

  3. Corrosion behavior of pristine and added MgB2 in Phosphate Buffered Saline Solution

    International Nuclear Information System (INIS)

    We have obtained by Spark Plasma Sintering (SPS), dense samples of MgB2 added with Ho2O3. Starting composition was (MgB2)0.975(HoO1.5)0.025 and we used addition powders with an average particle size below and above 100 nm. For Mg, pristine and added MgB2 samples we measured potentiodynamic polarization curves in Phosphate Buffered Saline (PBS) solution media at room temperature. MgB2 based composites show corrosion/ degradation effects. This behavior is in principle similar to Mg based alloys in the same media. Our work suggests that the different morphologies and phase compositions of the SPS-ed samples influence the interaction with corrosion medium; hence additions can play an important role in controlling the corrosion rate. Pristine MgB2 show a significant improvement of the corrosion resistance, if compared with Mg. The best corrosion resistance is obtained for pristine MgB2, followed by MgB2 with nano-Ho2O3 and μ-Ho2O3 additions.

  4. Consolidation of B4C-TaB2 eutectic composites by spark plasma sintering

    Directory of Open Access Journals (Sweden)

    Dmytro Demirskyi

    2015-12-01

    Full Text Available The in situ synthesis/consolidation of B4C-TaB2 eutectic composites by spark plasma sintering (SPS is reported. The microstructure–property relations were determined for composites with the B4C-TaB2 eutectic composition as functions of TaB2 content, and TaB2-TaB2 interlamellar spacing. A clear maximum in fracture toughness was identified (∼4.5 MPa m1/2 for eutectic composites with interlamellar spacing between 0.9 and 1.1 μm. The composites with the hypereutectic composition of 40 mol.% TaB2 obtained by SPS exhibited lower Vickers hardness (25–26 GPa but higher indentation fracture toughness (up to 4.9 MPa m1/2 than eutectic composites with 30–35 mol.% of TaB2.

  5. Atomic layer deposition of boron-containing films using B2F4

    International Nuclear Information System (INIS)

    Ultrathin and conformal boron-containing atomic layer deposition (ALD) films could be used as a shallow dopant source for advanced transistor structures in microelectronics manufacturing. With this application in mind, diboron tetrafluoride (B2F4) was explored as an ALD precursor for the deposition of boron containing films. Density functional theory simulations for nucleation on silicon (100) surfaces indicated better reactivity of B2F4 in comparison to BF3. Quartz crystal microbalance experiments exhibited growth using either B2F4-H2O for B2O3 ALD, or B2F4-disilane (Si2H6) for B ALD, but in both cases, the initial growth per cycle was quite low (≤0.2 Å/cycle) and decreased to near zero growth after 8–30 ALD cycles. However, alternating between B2F4-H2O and trimethyl aluminum (TMA)-H2O ALD cycles resulted in sustained growth at ∼0.65 Å/cycle, suggesting that the dense –OH surface termination produced by the TMA-H2O combination enhances the uptake of B2F4 precursor. The resultant boron containing films were analyzed for composition by x-ray photoelectron spectroscopy, and capacitance measurements indicated an insulating characteristic. Finally, diffused boron profiles less than 100 Å were obtained after rapid thermal anneal of the boron containing ALD film

  6. 关于B2B服务品牌忠诚度的研究%Research On The B2B Service Brand Loyalty

    Institute of Scientific and Technical Information of China (English)

    孔令明; 耿禧则

    2012-01-01

    对于品牌忠诚度的研究,过去一直局限于产品品牌上。将品牌忠诚度理论运用于B2B服务品牌,通过实证调查,研究品牌认知度与品牌形象对态度忠诚度和行动忠诚度的影响作用,并据此为B2B服务品牌的成功管理提出若干可行性方案。%For brand loyalty of research, the past has been confined to the product brand. This paper brand loyalty theory is applied to B2B service brand. Through the empirical research, the effect of the brand recognition and brand image to action loyalty and attitude loyalty, And put forward some feasible solutions of the B2B service brand management .

  7. Depletion of the xynB2 gene upregulates β-xylosidase expression in C. crescentus.

    Science.gov (United States)

    Corrêa, Juliana Moço; Mingori, Moara Rodrigues; Gandra, Rinaldo Ferreira; Loth, Eduardo Alexandre; Seixas, Flávio Augusto Vicente; Simão, Rita de Cássia Garcia

    2014-01-01

    Caulobacter crescentus is able to express several enzymes involved in the utilization of lignocellulosic biomasses. Five genes, xynB1-5, that encode β-xylosidases are present in the genome of this bacterium. In this study, the xynB2 gene, which encodes β-xylosidase II (CCNA_02442), was cloned under the control of the PxylX promoter to generate the O-xynB2 strain, which overexpresses the enzyme in the presence of xylose. In addition, a null mutant strain, Δ-xynB2, was created by two homologous recombination events where the chromosomal xynB2 gene was replaced by a copy that was disrupted by the spectinomycin-resistant cassette. We demonstrated that C. crescentus cells lacking β-xylosidase II upregulates the xynB genes inducing β-xylosidase activity. Transcriptional analysis revealed that xynB1 (RT-PCR analysis) and xynB2 (lacZ transcription fusion) gene expression was induced in the Δ-xynB2 cells, and high β-xylosidase activity was observed in the presence of different agro-industrial residues in the null mutant strain, a characteristic that can be explored and applied in biotechnological processes. In contrast, overexpression of the xynB2 gene caused downregulation of the expression and activity of the β-xylosidase. For example, the β-xylosidase activity that was obtained in the presence of sugarcane bagasse was 7-fold and 16-fold higher than the activity measured in the C. crescentus parental and O-xynB2 cells, respectively. Our results suggest that β-xylosidase II may have a role in controlling the expression of the xynB1 and xynB2 genes in C. crescentus. PMID:24142353

  8. Molecular cloning and characterization of SoxB2 gene from Zhikong scallop Chlamys farreri

    Science.gov (United States)

    He, Yan; Bao, Zhenmin; Guo, Huihui; Zhang, Yueyue; Zhang, Lingling; Wang, Shi; Hu, Jingjie; Hu, Xiaoli

    2013-11-01

    The Sox proteins play critical roles during the development of animals, including sex determination and central nervous system development. In this study, the SoxB2 gene was cloned from a mollusk, the Zhikong scallop ( Chlamys farreri), and characterized with respect to phylogeny and tissue distribution. The full-length cDNA and genomic DNA sequences of C. farreri SoxB2 ( Cf SoxB2) were obtained by rapid amplification of cDNA ends and genome walking, respectively, using a partial cDNA fragment from the highly conserved DNA-binding domain, i.e., the High Mobility Group (HMG) box. The full-length cDNA sequence of Cf SoxB2 was 2 048 bp and encoded 268 amino acids protein. The genomic sequence was 5 551 bp in length with only one exon. Several conserved elements, such as the TATA-box, GC-box, CAAT-box, GATA-box, and Sox/sry-sex/testis-determining and related HMG box factors, were found in the promoter region. Furthermore, real-time quantitative reverse transcription PCR assays were carried out to assess the mRNA expression of Cf SoxB 2 in different tissues. SoxB2 was highly expressed in the mantle, moderately in the digestive gland and gill, and weakly expressed in the gonad, kidney and adductor muscle. In male and female gonads at different developmental stages of reproduction, the expression levels of Cf SoxB2 were similar. Considering the specific expression and roles of SoxB 2 in other animals, in particular vertebrates, and the fact that there are many pallial nerves in the mantle, cerebral ganglia in the digestive gland and gill nerves in gill, we propose a possible essential role in nervous tissue function for Sox B 2 in C. farreri.

  9. Endogenous ephrinB2 mediates colon-urethra cross-organ sensitization via Src kinase-dependent tyrosine phosphorylation of NR2B.

    Science.gov (United States)

    Peng, Hsien-Yu; Chen, Gin-Den; Lai, Cheng-Hung; Tung, Kwong-Chung; Chang, Junn-Liang; Lin, Tzer-Bin

    2010-01-01

    Recently, the role of EphB receptor (EphBR) tyrosine kinase and their ephrinB ligands in spinal pain-related neural plasticity has been identified. To test whether Src-family non-receptor tyrosine kinase-dependent glutamatergic N-methyl-d-aspartate receptor (NMDAR) NR2B subunit phosphorylation underlies lumbosacral spinal EphBR activation to mediate cross-organ sensitization between the colon and the urethra, external urethra sphincter electromyogram activity evoked by pelvic nerve stimulation and protein expression in the lumbosacral (L6-S2) dorsal horn were studied before and after intracolonic mustard oil (MO) instillation. We found MO instillation produced colon-urethra reflex sensitization along with an upregulation of endogenous ephrinB2 expression as well as phosphorylation of EphB 1/2, Src-family kinase, and NR2B tyrosine residues. Intrathecal immunoglobulin fusion protein of EphB1 and EphB2 as well as PP2 reversed the reflex sensitization and NR2B phosphorylation caused by MO. All these results suggest that EphBR-ephrinB interactions, which provoke Src-family kinase-dependent NMDAR NR2B phosphorylation at the lumbosacral spinal cord level, are involved in cross-organ sensitization, contributing to the development of viscero-visceral referred pain between the bowel and the urethra. PMID:19864302

  10. Structural, Elastic, and Electronic Properties of ReB2: A First-Principles Calculation

    Directory of Open Access Journals (Sweden)

    Run Long

    2008-02-01

    Full Text Available The structural, elastic, and electronic properties of the hard material ReB2 have been investigated by means of density functional theory. The calculated equilibrium structural parameters of ReB2 are in agreement with the experimental results. Our result of bulk modulus shows that it is a low compressible material. Furthermore, the elastic anisotropy is discussed by investigating the elastic stiffness constants. The charge density and the electronic properties indicate that the covalent bonding of Re-B and B-B plays an important role in formation of a hard material. The good metallicity and hardness of ReB2 might serve as hard conductors.

  11. EphB2 SNPs and Sporadic Prostate Cancer Risk in African American Men

    OpenAIRE

    Christiane M Robbins; Stanley Hooker; Kittles, Rick A.; John D. Carpten

    2011-01-01

    The EphB2 gene has been implicated as a tumor suppressor gene somatically altered in both prostate cancer (PC) and colorectal cancer. We have previously shown an association between an EphB2 germline nonsense variant and risk of familial prostate cancer among African American Men (AAM). Here we set out to test the hypothesis that common variation within the EphB2 locus is associated with increased risk of sporadic PC in AAM. We genotyped a set of 341 single nucleotide polymorphisms (SNPs) enc...

  12. Investigating affordances of virtual worlds for real world B2C e-commerce

    OpenAIRE

    Tran, Minh; Minocha, Shailey; Roberts, Dave; Laing, Angus; Langdridge, Darren

    2011-01-01

    Virtual worlds are three-dimensional (3D) online persistent multi-user environments where users interact through avatars. The literature suggests that virtual worlds can facilitate real world business-to-consumer (B2C) e-commerce. However, few real world businesses have adopted virtual worlds for B2C e-commerce. In this paper, we present results from interviews with consumers in a virtual world to investigate how virtual worlds can support B2C e-commerce. A thematic analysis of the data was c...

  13. Competition in B2C eCommerce: Analytical Issues and Empirical Evidence

    OpenAIRE

    Schmitz, Stefan W.; Michael Latzer

    2002-01-01

    This paper questions the widely held view that B2C eCommerce markets are characterised by a high intensity of competition, using a mixture of theoretical arguments and empirical evidence. We discuss two hypothesis and survey empirical studies which test them. We argue that the goods sold in B2C eCommerce have to be interpreted as heterogeneous “composite goods”, that market transparency in B2C eCommerce is lower than widely assumed, and that high endogenous sunk costs limit the intensity of c...

  14. B2C eCommerce Strategy and Market Structure: The Survey Based Approach

    OpenAIRE

    Sint, Peter Paul; Schmitz, Stefan W.

    2003-01-01

    This paper follows two objectives: (i) It demonstrates the merits of the survey based approach to B2C eCommerce characteristics and company strategy, and (ii) it presents empirical evidence of the crucial importance of size and marketing investment in B2C eCommerce markets. It presents econometric estimates of the effects of company characteristics and company strategies on the performance of Viennese B2C eCommerce companies in 2001. We provide econometric analysis of three dependent variable...

  15. Improving magnetic properties of MgB2 bulk superconductors by synthetic engine oil treatment

    Science.gov (United States)

    Taylan Koparan, E.; Savaskan, B.; Yanmaz, E.

    2016-08-01

    The present study focuses on the effects of standby time of the MgB2 samples immersed in synthetic engine oil on the critical current density (Jc(H)), magnetic field dependence of the pinning force density fp(b) and Tc performances of MgB2 bulk superconductors. Synthetic engine oil was used as a product which is cheap and a rich carbon source. Manufactured MgB2 pellet samples were immersed at different standby time of 30 min, 120 min, 300 min and 1440 min in synthetic engine oil after the first heating process. Finally, MgB2 samples immersed in synthetic engine oil were sintered at 1000 °C and kept for 15 min in Ar atmosphere. The critical current density of all of MgB2 samples immersed at different standby time in engine oil in whole field range was better than that of the pure MgB2 sample because of the number of the pinning centers. The MgB2 sample immersed at 300 min standby time in synthetic engine oil has the best performance compared to other samples. The Jc value for the pure sample is 2.0 × 103 A/cm2, whereas for the MgB2 sample immersed at 300 min standby time in engine oil the Jc is enhanced to 4.8 × 103A/cm2 at 5 K and 3 T. The superconducting transition temperature (Tc) did not change with the increasing standby time of the samples in synthetic engine oil at all. The best diamagnetic property was obtained from the sample which kept in synthetic engine oil for 300 min. Synthetic engine oil treatment results in remarkable improvement of the critical current density and pinning force performances of MgB2 superconductors. It was found that all MgB2 samples have a different pinning property at different measuring temperatures. Using synthetic engine oil as a product which is cheap and a rich carbon source in MgB2 bulk superconductors makes MgB2 samples immersed in synthetic engine oil a good candidate for industrial applications.

  16. The b2c e-commerce landscape of the Dutch retail sector

    OpenAIRE

    Weltevreden, Jesse; De Kruijf, Karlijn; Atzema, Oedzge; Frenken, Koen; van Oort, Frank

    2005-01-01

    Business-to-consumer (b2c) e-commerce can be regarded as a disruptive process innovation that can make existing business models obsolete. B2c e-commerce provides retailers the possibility of a new service concept, new client interface and even delivery system. The history of retailing is replete of such innovations, like the introduction of department stores, mail order etcetera. It is only recently that researchers from various disciplines are examining the way retailers respond to b2c e-com...

  17. The Importance of Brand on B2B Markets: Case Study of Hilti

    OpenAIRE

    Konečný, Martin

    2012-01-01

    The brand is mostly associated with business-to-customer markets and environment. People would first think of such a brand, because we see marketing and advertising of those brands every day. But business-to-business brands are for companies also very important. The overall goal of my thesis would be to find out how the managers of a pure B2B company perceive the importance of brand in the B2B environment where the company operates. Theoretical part will, in the first chapter, characterize B2...

  18. B2B-yrityksen markkinointi, viestintä ja asiakaspalvelu sosiaalisessa mediassa

    OpenAIRE

    Liespuu, Mikael

    2014-01-01

    Tämän opinnäytetyön tarkoituksena oli tehdä tutkimus sosiaalisen median hyödyntämisestä B2B-yrityksessä. Tarkemmin lähestytään yrityksen markkinointia, viestintää sekä asiakaspalvelua sosiaalisessa mediassa. Sosiaalinen media mielletään usein kuluttajasuuntautuneeksi ja sitä se on aiemmin pääosin ollutkin. Tarkoituksena oli selvittää miten B2B-markkinoilla toimiva yritys saa enemmän irti sosiaalisesta mediasta. Ongelmana B2B-yritykselle sosiaalisen median osalta on se, että sosiaalisest...

  19. A B2B Digital Marketing Plan for a Micro Design Company

    OpenAIRE

    Yin, Zi

    2015-01-01

    This product-based thesis was made for a Finnish micro design company – 2.Elämä Design. The objective of the thesis is to create a strategic B2B digital marketing plan for 2.Elämä Design in order to help its business expansion in Finland and globally. The final product of the thesis is a handbook of B2B digital marketing 2.Elämä Design could put into use in 2015. The author set up five project tasks in order to accomplish the thesis project. Firstly a thorough literature review on B2B di...

  20. Varainhankintatuotteiden B2B-markkinointi sosiaalisessa mediassa Case: MKV Oy

    OpenAIRE

    Varvi, Tony

    2014-01-01

    Opinnäytetyössä käsitellään B2B- eli business-to-business-markkinointia sosiaalisessa mediassa. Toimeksiantajana opinnäytetyössä toimii MKV Oy, joka valmistaa, tuottaa ja myy yksilöityjä varainhankitatuotteita erilaisille organisaatioille. Yrityksen kohdeasiakkaita ovat erilaiset urheiluseurat, minkä takia yrityksen toiminta on B2B-toimintaa. Sosiaalista mediaa tarkastellaan eri näkökulmista sekä yleisesti että B2B-markkinointikeinona ja –kanavana. Työssä on käytetty lähteinä sekä kirjallisia...

  1. X-ray Photoelectron Spectroscopy Studies of MgB2 for Valence State of Mg

    OpenAIRE

    Talapatra, A.; Bandyopadhyay, S K; Sen, Pintu; P. Barat; S. Mukherjee; Mukherjee, M.(Variable Energy Cyclotron Centre, Kolkata, India)

    2004-01-01

    Core level X-ray Photoelectron Spectroscopy (XPS) studies have been carried out on polycrystalline MgB_2 pellets over the whole binding energy range with a view to having an idea of the charge state of Magnesium (Mg). We observe 3 distinct peaks in Mg 2p spectra at 49.3 eV (trace), 51.3 eV (major) and 54.0 eV (trace), corresponding to metallic Mg, MgB_2 and MgCO_3 or, divalent Mg species respectively. Similar trend has been noticed in Mg 2s spectra. The binding energy of Mg in MgB_2 is lower ...

  2. Hg Substitution Effect on Superconductivity and Crystal Structure of MgB2

    Institute of Scientific and Technical Information of China (English)

    Ya-Jing Cui; Yong-Liang Chen; Ye Yang; Yong Zhang; Cui-Hua Cheng; Yong Zhao

    2008-01-01

    Polycrystalline Mg1-xHgxB2 samples with x=0, 1%, 2.5%, 5%, 7.5%, and 10% have been synthe- sized by solid-state reaction. Different from the substitu- tion effect of Al, C, Li, etc. on crystal structure of MgB2, Hg substitution for Mg results in an increase of the lattice constant in both a and c directions. The super- conductivity of MgB2 is also suppressed by Hg substi- tution. The observed suppression of super- conductivity by Hg substitution is discussed in terms of the interband impurity scattering effect in two-band superconductors.

  3. Anomalous magnetic susceptibility of antiferromagnetic TbB2C2

    International Nuclear Information System (INIS)

    We measured the magnetic susceptibilities of TbB2C2 under fields along the , and directions. The susceptibilities below TN exhibit clear twofold symmetry in the (0 0 1) plane. No spontaneous magnetization in TbB2C2 indicates that this anisotropy in the tetragonal basal plane reflects parallel and perpendicular susceptibilities of an antiferromagnet. The susceptibilities of the and [1 1 0] directions show no cusp-like anomaly but anomalous upturns below TN with decreasing temperature, though TbB2C2 is confirmed to be an antiferromagnet. (author)

  4. Interaction in the ternary system Bi2O3-B2O3-Zno

    International Nuclear Information System (INIS)

    The authors have investigated the Bi2O3-B2O3-ZnO system along section between the starting components which were bismuth borate and zinc borate, including additionally the compound 3ZnO.B2O3. The presence of polymorphic transformation was noted in the phase at 9640C and x-ray diffraction data were provided for both modifications. The investigations performed here on both the binary phase 3Zn0.B2O3 and on the ternary system confirm the presence of the polymorphic transformation in them at 9400C and the x-ray diffraction data

  5. Tyrosine kinase signalling in breast cancer: ErbB family receptor tyrosine kinases

    International Nuclear Information System (INIS)

    ERBB family receptor tyrosine kinases are overexpressed in a significant subset of breast cancers. One of these receptors, HER2/neu, or ErbB-2, is the target for a new rational therapeutic antibody, Herceptin. Other inhibitors that target this receptor, and another family member, the epidermal growth factor (EGF) receptor, are moving into clinical trials. Both of these receptors are sometimes overexpressed in breast cancer, and still subject to regulation by hormones and other physiological regulators. Optimal use of therapeutics targeting these receptors will require consideration of the several modes of regulation of these receptors and their interactions with steroid receptors

  6. Safety Analysis Report: X17B2 beamline Synchrotron Medical Research Facility

    International Nuclear Information System (INIS)

    This report contains a safety analysis for the X17B2 beamline synchrotron medical research facility. Health hazards, risk assessment and building systems are discussed. Reference is made to transvenous coronary angiography

  7. A novel B-2 suppressor cell regulating susceptibility/resistance of mice to toxoplasma gondii infection

    International Nuclear Information System (INIS)

    Irradiation treatment enhanced resistance of C57BL/6, but not BALB/c against Toxoplasma gondii infection. Six Gy-irradiated (IR) C57BL/6 recipients of B-2 cells from T. gondii-infected C57BL/6 died after infection. B-2 suppressor cells from infected C57BL/6 enhanced production of IL-4 and IL-10 in peritoneal exudate cells (PECs), and down-regulated NO release in peritoneal macrophages after infection. On the other hand, B-2 suppressor cells were not detected in a strain, BALB/c, resistant against infection. These data indicated that irradiation-sensitive B-2 cells regulated susceptibility/resistance in mice against T. gondii infection. (author)

  8. Molecular-Beam Epitaxially Grown MgB2 Thin Films and Superconducting Tunnel Junctions

    International Nuclear Information System (INIS)

    Since the discovery of its superconducting properties in 2001, magnesium diboride has generated terrific scientific and engineering research interest around the world. With a TC of 39K and two superconducting gaps, MgB2 has great promise from the fundamental point of view, as well as immediate applications. Several techniques for thin film deposition and heterojunction formation have been established, each with its own advantages and drawbacks. Here, we will present a brief overview of research based on MgB2 thin films grown by molecular beam epitaxy coevaporation of Mg and B. The films are smooth and highly crystalline, and the technique allows for virtually any heterostructure to be formed, including all-MgB2 tunnel junctions. Such devices have been characterized, with both quasiparticle and Josephson tunneling reported. MgB2 remains a material of great potential for a multitude of further characterization and exploration research projects and applications.

  9. Intestinal colonization with phylogenetic group B2 Escherichia coli related to inflammatory bowel disease

    DEFF Research Database (Denmark)

    Petersen, Andreas Munk; Halkjær, Sofie Ingdam; Gluud, Lise Lotte

    2015-01-01

    on 163 patients with IBD and 89 controls. Among IBD patients, 57 patients had ulcerative colitis (UC) and 95 Crohn's disease (CD). Random-effects meta-analysis showed that IBD patients were more likely to have B2 E. coli intestinal colonization compared with controls (odds ratio [OR]: 2.28; 95......BACKGROUND AND OBJECTIVES: Increased numbers of Escherichia coli and, furthermore, specific subtypes of E. coli, such as E. coli of the phylogenetic groups B2 and D have been found in the intestine of patients with inflammatory bowel disease (IBD). In this review, we wanted to evaluate the...... relationship between B2 and D E. coli intestinal colonization and IBD. METHODS: A systematic review with meta-analyses. We included studies comparing colonization with B2 and D E. coli in IBD patients and in controls. Random-effects and fixed-effect meta-analyses were performed. RESULTS: We included 7 studies...

  10. Observation and Properties of L=1 B_1 and B_2* Mesons

    CERN Document Server

    Abazov, V M; Abolins, M; Acharya, B S; Adams, M; Adams, T; Aguiló, E; Ahn, S H; Ahsan, M; Alexeev, G D; Alkhazov, G; Alton, A; Alverson, G; Alves, G A; Anastasoaie, M; Ancu, L S; Andeen, T; Anderson, S; Andrieu, B; Anzelc, M S; Arnoud, Y; Arov, M; Arthaud, M; Askew, A; Åsman, B; Assis-Jesus, A C S; Atramentov, O; Autermann, C; Avila, C; Ay, C; Badaud, F; Baden, A; Bagby, L; Baldin, B; Bandurin, D V; Banerjee, S; Banerjee, P; Barberis, E; Barfuss, A F; Bargassa, P; Baringer, P; Barreto, J; Bartlett, J F; Bassler, U; Bauer, D; Beale, S; Bean, A; Begalli, M; Begel, M; Belanger-Champagne, C; Bellantoni, L; Bellavance, A; Benítez, J A; Beri, S B; Bernardi, G; Bernhard, R; Berntzon, L; Bertram, I; Besançon, M; Beuselinck, R; Bezzubov, V A; Bhat, P C; Bhatnagar, V; Biscarat, C; Blazey, G; Blekman, F; Blessing, S; Bloch, D; Bloom, K; Böhnlein, A; Boline, D; Bolton, T A; Borissov, G; Bos, K; Bose, T; Brandt, A; Brock, R; Brooijmans, G; Bross, A; Brown, D; Buchanan, N J; Buchholz, D; Bühler, M; Büscher, V; Burdin, S; Burke, S; Burnett, T H; Buszello, C P; Butler, J M; Calfayan, P; Calvet, S; Cammin, J; Caron, S; Carvalho, W; Casey, B C K; Cason, N M; Castilla-Valdez, H; Chakrabarti, S; Chakraborty, D; Chan, K M; Chan, K; Chandra, A; Charles, F; Cheu, E; Chevallier, F; Cho, D K; Choi, S; Choudhary, B; Christofek, L; Christoudias, T; Cihangir, S; Claes, D; Clément, C; Clement, B; Coadou, Y; Cooke, M; Cooper, W E; Corcoran, M; Couderc, F; Cousinou, M C; Crepe-Renaudin, S; Cutts, D; Cwiok, M; Da Motta, H; Das, A; Davies, G; De, K; De Jong, S J; de Jong, P; De La Cruz-Burelo, E; De Oliveira Martins, C; Degenhardt, J D; Déliot, F; Demarteau, M; Demina, R; Denisov, D; Denisov, S P; Desai, S; Diehl, H T; Diesburg, M; Dominguez, A; Dong, H; Dudko, L V; Duflot, L; Dugad, S R; Duggan, D; Duperrin, A; Dyer, J; Dyshkant, A; Eads, M; Edmunds, D; Ellison, J; Elvira, V D; Enari, Y; Eno, S; Ermolov, P; Evans, H; Evdokimov, A; Evdokimov, V N; Ferapontov, A V; Ferbel, T; Fiedler, F; Filthaut, F; Fisher, W; Fisk, H E; Ford, M; Fortner, M; Fox, H; Fu, S; Fuess, S; Gadfort, T; Galea, C F; Gallas, E; Galyaev, E; García, C; García-Bellido, A; Gavrilov, V; Gay, P; Geist, W; Gelé, D; Gerber, C E; Gershtein, Yu; Gillberg, D; Ginther, G; Gollub, N; Gómez, B; Goussiou, A; Grannis, P D; Greenlee, H; Greenwood, Z D; Gregores, E M; Grenier, G; Gris, P; Grivaz, J F; Grohsjean, A; Grünendahl, S; Grünewald, M W; Guo, J; Guo, F; Gutíerrez, P; Gutíerrez, G; Haas, A; Hadley, N J; Haefner, P; Hagopian, S; Haley, J; Hall, I; Hall, R E; Han, L; Hanagaki, K; Hansson, P; Harder, K; Harel, A; Harrington, R; Hauptman, J M; Hauser, R; Hays, J; Hebbeker, T; Hedin, D; Hegeman, J G; Heinmiller, J M; Heinson, A P; Heintz, U; Hensel, C; Herner, K; Hesketh, G; Hildreth, M D; Hirosky, R; Hobbs, J D; Hoeneisen, B; Hoeth, H; Hohlfeld, M; Hong, S J; Hooper, R; Hossain, S; Houben, P; Hu, Y; Hubacek, Z; Hynek, V; Iashvili, I; Illingworth, R; Ito, A S; Jabeen, S; Jaffré, M; Jain, S; Jakobs, K; Jarvis, C; Jesik, R; Johns, K; Johnson, C; Johnson, M; Jonckheere, A; Jonsson, P; Juste, A; Käfer, D; Kahn, S; Kajfasz, E; Kalinin, A M; Kalk, J R; Kalk, J M; Kappler, S; Karmanov, D; Kasper, J; Kasper, P; Katsanos, I; Kau, D; Kaur, R; Kaushik, V; Kehoe, R; Kermiche, S; Khalatyan, N; Khanov, A; Kharchilava, A I; Kharzheev, Yu M; Khatidze, D; Kim, H; Kim, T J; Kirby, M H; Kirsch, M; Klima, B; Kohli, J M; Konrath, J P; Kopal, M; Korablev, V M; Kothari, B; Kozelov, A V; Krop, D; Kryemadhi, A; Kühl, T; Kumar, A; Kunori, S; Kupco, A; Kurca, T; Kvita, J; Lacroix, F; Lam, D; Lammers, S; Landsberg, G L; Lazoflores, J; Lebrun, P; Lee, W M; Leflat, A; Lehner, F; Lellouch, J; Lesne, V; Lévêque, J; Lewis, P; Li, J; Li, Q Z; Li, L; Lietti, S M; Lima, J G R; Lincoln, D; Linnemann, J; Lipaev, V V; Lipton, R; Liu, Y; Liu, Z; Lobo, L; Lobodenko, A; Lokajícek, M; Lounis, A; Love, P; Lubatti, H J; Lyon, A L; Maciel, A K A; Mackin, D; Madaras, R J; Mättig, P; Magass, C; Magerkurth, A; Makovec, N; Mal, P K; Malbouisson, H B; Malik, S; Malyshev, V L; Mao, H S; Maravin, Y; Martin, B; McCarthy, R; Melnitchouk, A; Mendes, A; Mendoza, L; Mercadante, P G; Merkin, M; Merritt, K W; Meyer, J; Meyer, A; Michaut, M; Millet, T; Mitrevski, J; Molina, J; Mommsen, R K; Mondal, N K; Moore, R W; Moulik, T; Muanza, G S; Mulders, M; Mulhearn, M; Mundal, O; Mundim, L; Nagy, E; Naimuddin, M; Narain, M; Naumann, N A; Neal, H A; Negret, J P; Neustroev, P; Nilsen, H; Nomerotski, A; Novaes, S F; Nunnemann, T; O'Dell, V; O'Neil, D C; Obrant, G; Ochando, C; Onoprienko, D; Oshima, N; Osta, J; Otec, R; Oteroy-Garzon, G J; Owen, M; Padley, P; Pangilinan, M; Parashar, N; Park, S J; Park, S K; Parsons, J; Partridge, R; Parua, N; Patwa, A; Pawloski, G; Penning, B; Perea, P M; Peters, K; Peters, Y; Petroff, P; Petteni, M; Piegaia, R; Piper, J; Pleier, M A; Podesta-Lerma, P L M; Podstavkov, V M; Pogorelov, Y; Pol, M E; Polozov, P; Pompo, A; Pope, B G; Popov, A V; Potter, C; Prado da Silva, W L; Prosper, H B; Protopopescu, S D; Qian, J; Quadt, A; Quinn, B; Rakitine, A; Rangel, M S; Rani, K J; Ranjan, K; Ratoff, P N; Renkel, P; Reucroft, S; Rich, P; Rijssenbeek, M; Ripp-Baudot, I; Rizatdinova, F K; Robinson, S; Rodrigues, R F; Royon, C; Rubinov, P; Ruchti, R; Safronov, G; Sajot, G; Sánchez-Hernández, A; Sanders, M P; Santoro, A F S; Savage, G; Sawyer, L; Scanlon, T; Schaile, A D; Schamberger, R D; Scheglov, Y; Schellman, H; Schieferdecker, P; Schliephake, T; Schmitt, C; Schwanenberger, C; Schwartzman, A; Schwienhorst, R; Sekaric, J; Sen-Gupta, S; Severini, H; Shabalina, E; Shamim, M; Shary, V; Shchukin, A A; Shivpuri, R K; Shpakov, D; Siccardi, V; Simák, V; Sirotenko, V I; Skubic, P L; Slattery, P F; Smirnov, D; Smith, R P; Snow, J; Snow, G R; Snyder, S; Söldner-Rembold, S; Sonnenschein, L; Sopczak, A; Sosebee, M; Soustruznik, K; Souza, M; Spurlock, B; Stark, J; Steele, J; Stolin, V; Stone, A; Stoyanova, D A; Strandberg, J; Strandberg, S; Strang, M A; Strauss, M; Strauss, E; Ströhmer, R; Strom, D; Strovink, M; Stutte, L; Sumowidagdo, S; Svoisky, P; Sznajder, A; Talby, M; Tamburello, P; Tanasijczuk, A; Taylor, W; Telford, P; Temple, J; Tiller, B; Tissandier, F; Titov, M; Tokmenin, V V; Tomoto, M; Toole, T; Torchiani, I; Trefzger, T; Tsybychev, D; Tuchming, B; Tully, C; Tuts, P M; Unalan, R; Uvarov, S; Uvarov, L; Uzunyan, S; Vachon, B; Van den Berg, P J; van Eijk, B; Van Kooten, R; Van Leeuwen, W M; Varelas, N; Varnes, E W; Vartapetian, A H; Vasilyev, I A; Vaupel, M; Verdier, P; Vertogradov, L S; Verzocchi, M; Villeneuve-Séguier, F; Vint, P; Vokac, P; Von Törne, E; Voutilainen, M; Vreeswijk, M; Wagner, R; Wahl, H D; Wang, L; Wang, M H L; Warchol, J; Watts, G; Wayne, M; Weber, M; Weber, G; Weerts, H; Wenger, A; Wermes, N; Wetstein, M; White, A; Wicke, D; Wilson, G W; Williams, M R J; Wimpenny, S J; Wobisch, M; Wood, D R; Wyatt, T R; Xie, Y; Yacoob, S; Yamada, R; Yan, M; Yasuda, T; Yatsunenko, Y A; Yip, K; Yoo, H D; Youn, S W; Yu, J; Yu, C; Yurkewicz, A; Zatserklyaniy, A; Zeitnitz, C; Zhang, D; Zhao, T; Zhou, B; Zhu, J; Zielinski, M; Zieminska, D; Zieminski, A; Zivkovic, L; Zutshi, V; Zverev, E G

    2007-01-01

    Excited B mesons B_1 and B_2* are observed directly for the first time as two separate states in fully reconstructed decays to B+(*) pi-. The mass of B_1 is measured to be (5720.6 +- 2.4 +- 1.4) MeV/c^2 and the mass difference DeltaM between B_2* and B_1 is (26.2 +- 3.1 +- 0.9) MeV/c^2, giving the mass of the B_2* as (5746.8 +- 2.4 +- 1.7) MeV/c^2. The production rate for B_1 and B_2* mesons is determined to be a fraction (13.9 +- 1.9 +- 3.2)% of the production rate of the B+ meson.

  11. Properties of MgB2 wires made by internal magnesium diffusion into different boron powders

    Science.gov (United States)

    Kováč, P.; Hušek, I.; Rosova, A.; Kulich, M.; Melišek, T.; Kopera, L.; Brunner, B.

    2015-09-01

    Different boron powders were used for MgB2 wires manufactured by internal magnesium diffusion. The structure of the MgB2 core, critical temperature and critical currents of Cu/Ti sheathed wires differing only in boron powder were analyzed and compared. It was found that the particle size and purity of boron powders influence the creation of the MgB2 phase and, consequently, also considerably influence its superconducting properties. The highest critical current density in the low external field was measured for wire with a boron purity of 98.5% produced by Pavezyum. It was used also for stabilized multi-core MgB2 wire with high engineering current densities in low magnetic fields at 20 K, which may be attractive for some low field applications, e.g. high-power wind generators.

  12. Managing Innovation Through Social Media in B2B SME-Context

    DEFF Research Database (Denmark)

    Lutz, Salla; Madsen, Svend Ole; Brink, Tove

    2015-01-01

    This paper shed light on how social media application can enhance innovation management in SME B2B context. Our study employs a qualitative case study approach with four B2B SMEs for in-depth research in the period from October 2013 to October 2014. The B2B SME managers aim for open business model...... innovation. However, social media application is hindered due to lack of specific local knowledge, lack of knowledge on social media technicalities and bewilderedness on leadership approaches within the social media application. A contribution is hereby made to the B2B SME field, to the academic...... understanding an insight on social media application and open business model innovation....

  13. Proton Mobility in b2 Ion Formation and Fragmentation Reactions of Histidine-Containing Peptides

    Science.gov (United States)

    Nelson, Carissa R.; Abutokaikah, Maha T.; Harrison, Alex G.; Bythell, Benjamin J.

    2016-03-01

    A detailed energy-resolved study of the fragmentation reactions of protonated histidine-containing peptides and their b2 ions has been undertaken. Density functional theory calculations were utilized to predict how the fragmentation reactions occur so that we might discern why the mass spectra demonstrated particular energy dependencies. We compare our results to the current literature and to synthetic b2 ion standards. We show that the position of the His residue does affect the identity of the subsequent b2 ion (diketopiperazine versus oxazolone versus lactam) and that energy-resolved CID can distinguish these isomeric products based on their fragmentation energetics. The histidine side chain facilitates every major transformation except trans-cis isomerization of the first amide bond, a necessary prerequisite to diketopiperazine b2 ion formation. Despite this lack of catalyzation, trans-cis isomerization is predicted to be facile. Concomitantly, the subsequent amide bond cleavage reaction is rate-limiting.

  14. 实体市场支撑的B2B网站运营

    Institute of Scientific and Technical Information of China (English)

    李宋伟

    2008-01-01

    由于2007年至今一直在接触多个以实体市场为依托的大型B2B电子商务项目,也深入实体市场了解了市场环境和商户群体的网络营销实际需求,对实体市场开展电子商务项目有深刻的感触,现对以实体市场支撑的B2B网站运营与一般意义B2B网站(如阿里巴巴的综合B2B网站)运营做如下思考:

  15. Safety Analysis Report: X17B2 beamline Synchrotron Medical Research Facility

    Energy Technology Data Exchange (ETDEWEB)

    Gmuer, N.F.; Thomlinson, W.

    1990-02-01

    This report contains a safety analysis for the X17B2 beamline synchrotron medical research facility. Health hazards, risk assessment and building systems are discussed. Reference is made to transvenous coronary angiography. (LSP)

  16. Magnetic structures in RNi2B2C (R = Ho, Er) superconductors

    International Nuclear Information System (INIS)

    Single crystal neutron diffraction techniques have been employed to study the evolution of magnetic structures in RNi2B2C compounds in an attempt to understand the relationship between magnetic ordering and superconductivity in several members of this series. For HoNi2B2C, below the superconducting transition (Tc = 8 K), an incommensurate magnetic structure characterized by two wave vectors (0.585 a* and 0.915 c*) is found in a narrow temperature range between 4.7 K and 6 K. This is the same temperature range where bulk measurements find a deep minimum in the upper critical field, Hc2. Below 4.7 K, HoNi2B2C is a simple collinear antiferromagnet. ErNi2B2C (Tc = 11 K) orders in an incommensurate modulated antiferromagnetic state characterized by an ordering wave vector 0.553 a* below 7 K, which coexists with superconductivity

  17. Development of MgB2 superconductor wire with high critical current

    International Nuclear Information System (INIS)

    The MgB2 superconductor with smaller grain size could improve its critical properties by providing flux pinning centers with high grain boundary density. The effects of C doping such as charcoal, paper ash and glycerin on the superconducting properties was investigated for in situ processed MgB2 samples using low purity semi-crystalline B powder. The results show a decrease in Tc and an enhancement of Jc at high fields for the C-doped samples as compared to the un-doped samples. A combined process of a mechanical ball milling and liquid glycerin (C3H8O3) treatment of B powder has been conducted to enhance the superconducting properties of MgB2. The mechanical ball milling was effective for grain refinement, and a lattice disorder was easily achieved by glycerin addition. With the combined process, the critical properties was further increased due to a higher grain boundary density and a greater C substitution. To get fine grain structure of MgB2 with high critical current properties, mechanical milling for as-received B powder and low temperature solid-state reaction of 550 or 600 .deg. C were attempted to in situ powder-in-tube processed MgB2/Fe wires. The critical current properties of the MgB2 wires using the milled B powder were enhanced due to a smaller grain size and an increased volume of the superconducting phase. The solid-state reaction of a low temperature process for the samples using the milled B powder resulted in a poorer crystallinity with a smaller grain size, which improved superconducting properties. We established the system to measure the transport current properties of the MgB2 wires. The field dependence of the transport Jc was evaluated for the MgB2 wires heat-treated at different heat treatment conditions using ball-milled and glycerin-treated B powder. The MgB2 magnet was developed and the AC loss of MgB2 wire was also investigated. A conduction cooling device to cool the MgB2 coil down to 4 K has been fabricated and the coil was tested up

  18. Managers' perceptions of using of e-marketing in B2B relationships

    OpenAIRE

    Σαμαντά, Ειρήνη; Κυριαζόπουλος, Π.

    2008-01-01

    Researchers agree that the use of the Internet is increasingly expanding in business-tobusiness (B2B) relationships in order to improve effective communication, distribution, and streamline processes with customers and stakeholders. This study examines a sample of 30 firms operating in Greece and discusses the benefits from B2B collaboration by using e-marketing. The method used for the quantitative analysis is the factor analysis and ordinal symmetric measures; Kendall’s tau-b...

  19. Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition

    OpenAIRE

    Flores Juana M; Moreno-Bueno Gema; Cerutti Camilla; Pérez-Gómez Eduardo; Mira Emilia; Andradas Clara; Caffarel María M; García-Real Isabel; Palacios José; Mañes Santos; Guzmán Manuel; Sánchez Cristina

    2010-01-01

    Abstract Background ErbB2-positive breast cancer is characterized by highly aggressive phenotypes and reduced responsiveness to standard therapies. Although specific ErbB2-targeted therapies have been designed, only a small percentage of patients respond to these treatments and most of them eventually relapse. The existence of this population of particularly aggressive and non-responding or relapsing patients urges the search for novel therapies. The purpose of this study was to determine whe...

  20. An ANFIS-based on B2C electronic commerce transaction

    International Nuclear Information System (INIS)

    The purpose of this study is to use an adaptive-network-based fuzzy inference system to model a fuzzy logic-based system (FIS) for supporting decision-making process in B2C electronic commerce transaction. Firstly we introduce FIS in B2C electronic commerce transaction and ANFIS. Then we use ANFIS to model FIS with different membership functions(MF). Lastly we give a conclusion