Sample records for bradykinin b2 receptor

  1. Theoretical study of the human bradykinin-bradykinin B2 receptor complex. (United States)

    Gieldon, Artur; Lopez, Jakob J; Glaubitz, Clemens; Schwalbe, Harald


    The interaction of bradykinin (BK) with the bradykinin B2 receptor (B2R) was analyzed by using molecular modeling (MM) and molecular dynamics (MD) simulations. A homology model for B2R has been generated and the recently determined receptor-bound solid-state NMR spectroscopic structure of BK (Lopez et al., Angew. Chem. 2008, 120, 1692-1695; Angew. Chem. Int. Ed. 2008, 47, 1668-1671) has been modeled into the binding pocket of the receptor to probe the putative ligand-receptor interface. The experimental hormone structure fitted well into the binding pocket of the receptor model and remained stable during the MD simulation. We propose a parallel orientation of the side chains for Arg1 and Arg9 in BK that is bound to B2R. The MD simulation study also allows the conformational changes that lead to the activated form of B2R to be analyzed. The hydrogen bond between N140 (3.35) and W283 (6.48) is the key interaction that keeps the receptor in its inactive form. This hydrogen bond is broken during the MD simulation due to rotation of transmembrane helix 3 (TM3) and is replaced by a new hydrogen bond between W283 (6.48) and N324 (7.45). We propose that this interaction is specific for the activated form of the bradykinin B2 receptor. Additionally, we compared and discussed our putative model in the context of the structural model of the partially activated rhodopsin (Rh*) and with the known biochemical and structural data.

  2. The bradykinin B2 receptor in the early immune response against Listeria infection

    NARCIS (Netherlands)

    Kaman, W.E.; Wolterink, A.F.W.M.; Bader, M.; Boele, L.C.L.; Kleij, D. van der


    The endogenous danger signal bradykinin was recently found implicated in the development of immunity against parasites via dendritic cells. We here report an essential role of the B2 (B2R) bradykinin receptor in the early immune response against Listeria infection. Mice deficient in B2R (B2R-/- mice

  3. Effects of bradykinin B2 receptor stimulation at submucosal ganglia from rat distal colon. (United States)

    Avemary, Janine; Diener, Martin


    Bradykinin acts as an inflammatory mediator in the gut. In the present study we characterized bradykinin-induced changes in the intracellular calcium concentration ([Ca(2+)](i)) in whole-mount submucosal preparations from rat distal colon and examined the bradykinin receptors and subsequent signalling cascades involved. Bradykinin (2.10(-10)-2.10(-7)mol/l) evoked a concentration-dependent increase in [Ca(2+)](i) in about 90% of the investigated neurones. This Ca(2+) response was abolished by the bradykinin B(2) receptor antagonist HOE 140. The B(2) receptor agonist [Hyp(3)]-bradykinin mimicked the kinin response. In contrast, the B(1) receptor antagonist [des-Arg(10)]-HOE 140 and the B(1) receptor agonist bradykinin fragment 1-8 were ineffective. Immunohistochemical experiments confirmed the presence of bradykinin B(2) receptors in submucosal neurones. The effect of bradykinin on [Ca(2+)](i) was not mediated by a release of prostaglandins, as it was resistant against the cyclooxygenase inhibitor indomethacin. Blocking of G(q/11) proteins with YM-254890 suppressed the action of bradykinin, revealing that neuronal bradykinin B(2) receptors are coupled to this G protein. However, the subsequent signalling cascade differed from the classical phospholipase C signalling pathway, as the bradykinin response was resistant against the phospholipase C inhibitor U-73221, the ryanodine receptor antagonist dehydroryanodine, and only marginally sensitive against the blocker of IP(3)-receptors xestospongin C. Vice versa, the effect of bradykinin was nearly completely dependent on the presence of external Ca(2+) and could be reduced by lanthanum, a blocker of voltage-operated Ca(2+) channels, suggesting that the bradykinin-induced Ca(2+) response is achieved by an influx from the extracellular space via voltage-operated Ca(2+) channels.

  4. Advanced Modelling and Functional Characterization of B2 Bradykinin Receptor

    Directory of Open Access Journals (Sweden)

    Muhammad Saad Khan


    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.

  5. In Vivo Effects of Bradykinin B2 Receptor Agonists with Varying Susceptibility to Peptidases. (United States)

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


    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-[Hyp(3),Igl(5),Oic(7),Igl(8)]-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

  6. Effects of Bradykinin B2 Receptor Blockade on Infarct Size and Hemodynamics after Myocardial Infarction in Enalapril-treated Rats

    Institute of Scientific and Technical Information of China (English)

    Haizhu Zhang; Changcong Cui; Kexin Du; Jian Liu


    Objectives To study the effects of bradykinin (BK) B2 receptor blockade on infarct size and hemodynamics after myocardial infarction (MI) in rats with angiotensin-converting enzyme (ACE) inhibition therapy.Methods MI was produced by ligating the left coronary artery.The effects of enalapril(500μg/kg·day),enalapril(500μg/kg·day) with BK B2 receptor antagonist Hoe-140(500μg/kg·day),angiotensin Ⅱ(Ang Ⅱ) type 1(AT1) receptor antagonist losartan (3 mg/kg·day) on infarct size,left ventricular systolic pressure(LVSP),cardiac output index (CI) and stroke volume index (SVI) were observed in rats after MI.Treatments were started on the 2nd day after MI and continued for another 6 weeks.Results Enalapril reduced infarct size and improved CI and SVI compared with the untreated MI group (P<0.05 ),and these effects of enalapril were significantly blunted by concomitant treatment with Hoe-140 (P<0.05).Losartan was less effective than enalapril.LVSP were unchanged in the three treatment groups.Conclusions BK can reduce infract size and improve hemodynamics in rats following MI.The cardioprotective effects of ACEI partly result from the action of BK exerted through the B2 receptor.

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

    Directory of Open Access Journals (Sweden)

    Glen Daniel


    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

  8. 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;


    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...

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

    Directory of Open Access Journals (Sweden)

    Nur Bakir


    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.

  10. 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


    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

  11. Risk of bradykinin B2 receptor -58T/C gene polymorphism on hypertension: A meta-analysis. (United States)

    Luo, Kaiping; Yang, Pingping; Xu, Gaosi


    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.

  12. High-level expression and purification of the human bradykinin B(2) receptor in a tetracycline-inducible stable HEK293S cell line. (United States)

    Camponova, Paméla; Baud, Stéphanie; Mattras, Hélène; Duroux-Richard, Isabelle; Bonnafous, Jean-Claude; Marie, Jacky


    The B(2) bradykinin receptor belongs to the G-protein coupled receptor family. Development of new drugs for this important therapeutic target requires structural information on the receptor. The main goal of the present work was to overexpress the human B(2) receptor for future biophysical studies. Different tagged B(2) receptors were engineered and their properties were evaluated by transient expression in HEK293S cells. A B(2) receptor tagged with a hexahistidine at the N-terminus and a nonapeptide at the C-terminus was selected for high expression level and preserved ligand-binding characteristics. First, we generated a HEK293S stable cell line expressing the receptor constitutively at a level of 60pmol/mg of crude membrane protein. However, the decrease of expression level with cell passages led us to express the B(2) receptor in a HEK293S tetracycline-inducible stable cell line. Induction of expression of the B(2) receptor with tetracycline and sodium butyrate led to a level of 100pmol/mg of membrane protein, which is the highest level reported so far for this receptor. The expression level was stable with cell passages and the ligand-binding and signal transduction properties of the receptor were unaltered. The receptor was purified to near homogeneity by solubilization with n-dodecyl-beta-d-maltoside followed by a two-step purification procedure combining hydroxyapatite and immunoaffinity chromatography. Although the purified receptor is not functional, the purification of the B(2) receptor to near homogeneity from a stable cell line overexpressing this receptor pave the way for future structural studies of this receptor.

  13. Enhanced Ca(2+) response and stimulation of prostaglandin release by the bradykinin B2 receptor in human retinal pigment epithelial cells primed with proinflammatory cytokines. (United States)

    Catalioto, Rose-Marie; Valenti, Claudio; Maggi, Carlo Alberto; Giuliani, Sandro


    Kallikrein, kininogen and kinin receptors are present in human ocular tissues including the retinal pigment epithelium (RPE), suggesting a possible role of bradykinin (BK) in physiological and/or pathological conditions. To test this hypothesis, kinin receptors expression and function was investigated for the first time in human fetal RPE cells, a model close to native RPE, in both control conditions and after treatment with proinflammatory cytokines. Results showed that BK evoked intracellular Ca(2+) transients in human RPE cells by activating the kinin B2 receptor. Pretreatment of the cells with TNF-α and/or IL-1β enhanced Ca(2+) response in a time- and concentration-dependent additive manner, whereas the potency of BK and that of the selective B2 receptor antagonist, fasitibant chloride, both in the nanomolar range, remained unaffected. Cytokines have no significant effect on cell number and viability and on the activity of other GPCRs such as the kinin B1, acetylcholine, ATP and thrombin receptors. Immunoblot analysis and immunofluorescence studies revealed that cytokines treatment was associated with an increase in both kinin B2 receptor and COX-2 expression and with the secretion of prostaglandin E1 and E2 into the extracellular medium. BK, through activation of the kinin B2 receptor, potentiated the COX-2 mediated prostaglandin release in cytokines-primed RPE cells while new protein synthesis and prostaglandin production contribute to the potentiating effect of cytokines on BK-induced Ca(2+) response. In conclusion, overall data revealed a cross-talk between the kinin B2 receptor and cytokines in human RPE in promoting inflammation, a key feature in retinal pathologies including diabetic retinopathy and macular edema.

  14. Bradykinin B2 Receptors of dendritic cells, acting as sensors of kinins proteolytically released by Trypanosoma cruzi, are critical for the development of protective type-1 responses.

    Directory of Open Access Journals (Sweden)

    Ana Carolina Monteiro


    Full Text Available Although the concept that dendritic cells (DCs recognize pathogens through the engagement of Toll-like receptors is widely accepted, we recently suggested that immature DCs might sense kinin-releasing strains of Trypanosoma cruzi through the triggering of G-protein-coupled bradykinin B2 receptors (B2R. Here we report that C57BL/6.B2R-/- mice infected intraperitoneally with T. cruzi display higher parasitemia and mortality rates as compared to B2R+/+ mice. qRT-PCR revealed a 5-fold increase in T. cruzi DNA (14 d post-infection [p.i.] in B2R-/- heart, while spleen parasitism was negligible in both mice strains. Analysis of recall responses (14 d p.i. showed high and comparable frequencies of IFN-gamma-producing CD4+ and CD8+ T cells in the spleen of B2R-/- and wild-type mice. However, production of IFN-gamma by effector T cells isolated from B2R-/- heart was significantly reduced as compared with wild-type mice. As the infection continued, wild-type mice presented IFN-gamma-producing (CD4+CD44+ and CD8+CD44+ T cells both in the spleen and heart while B2R-/- mice showed negligible frequencies of such activated T cells. Furthermore, the collapse of type-1 immune responses in B2R-/- mice was linked to upregulated secretion of IL-17 and TNF-alpha by antigen-responsive CD4+ T cells. In vitro analysis of tissue culture trypomastigote interaction with splenic CD11c+ DCs indicated that DC maturation (IL-12, CD40, and CD86 is controlled by the kinin/B2R pathway. Further, systemic injection of trypomastigotes induced IL-12 production by CD11c+ DCs isolated from B2R+/+ spleen, but not by DCs from B2R-/- mice. Notably, adoptive transfer of B2R+/+ CD11c+ DCs (intravenously into B2R-/- mice rendered them resistant to acute challenge, rescued development of type-1 immunity, and repressed TH17 responses. Collectively, our results demonstrate that activation of B2R, a DC sensor of endogenous maturation signals, is critically required for development of acquired

  15. Site-directed mutagenesis at the human B2 receptor and molecular modelling to define the pharmacophore of non-peptide bradykinin receptor antagonists. (United States)

    Meini, Stefania; Cucchi, Paola; Bellucci, Francesca; Catalani, Claudio; Faiella, Angela; Rotondaro, Luigi; Quartara, Laura; Giolitti, Alessandro; Maggi, Carlo Alberto


    Combining site-directed mutagenesis with information obtained from molecular modelling of the bradykinin (BK) human B2 receptor (hB2R) as derived from the bovine rhodopsin crystal structure [Science 289 (2000) 739], we previously defined a putative binding mode for the non-peptide B2 receptor antagonists, FR173657 and LF16-0687 [Can J Physiol Pharmacol 80 (2002) 303]. The present work is aimed to define the specific role of the quinoline moiety in the pharmacophore of these non-peptide antagonists. The effect of the mutations I110A, L114A (TM, transmembrane 3), W256A (TM6), F292A, Y295A and Y295F (TM7) was evaluated. None of the mutations affected the binding interaction of peptide ligands: the agonist BK and the peptide antagonist MEN 11270. The affinities in competing for [3H]-BK binding and in blocking the BK-induced IP production by the non-peptide antagonists LF16-0687 and FR173657 at the wild type and mutant receptors were analysed. While the affinities of LF16-0687 and FR173657 were crucially decreased at the I110A, Y295A, and Y295F mutants, the W256A mutation affected the affinity of the LF16-0687 only. The important contribution of the quinoline moiety was shown by the inability of an analogue of LF16-0687, lacking this moiety, to affect BK binding at the wild type receptor. On the other hand, the benzamidine group did not interact with mutated residues, since LF16-0687 analogues without this group or with an oxidated benzamidine displayed pairwise loss of affinity on wild type and mutated receptors. Further differences between FR173657 and LF16-0687 were highlighted at the I110 and Y295 mutants when comparing binding (pK(i)) and functional antagonist (pKB) affinity. First, the I110A mutation similarly impaired their binding affinity (250-fold), but at a less extent the antagonist potency of FR173657 only. Second, both the hydroxyl and the phenyl moieties of the Y295 residue had a specific role in the LF16-0687 interaction with the receptor, as

  16. Activation of ERK, JNK, Akt, and G-protein coupled signaling by hybrid angiotensin II AT1/bradykinin B2 receptors expressed in HEK-293 cells

    DEFF Research Database (Denmark)

    Yu, Jun; Lubinsky, David; Tsomaia, Natia;


    Bradykinin (BK) and angiotensin II (AngII) often have opposite roles in cardiovascular diseases. Our aim here was to construct hybrid receptors which bind AngII but signal as BK. Various sequences of the intracellular face of the AngII type I receptor, AT1R, were replaced with corresponding...

  17. Regulation of bradykinin receptor gene expression in human lung fibroblasts. (United States)

    Phagoo, S B; Yaqoob, M; Herrera-Martinez, E; McIntyre, P; Jones, C; Burgess, G M


    In WI-38 human fibroblasts, interleukin-1 beta and tumour necrosis factor-alpha (TNF-alpha) increased bradykinin B(1) receptor mRNA, which peaked between 2 and 4 h, remaining elevated for 20 h. Binding of the bradykinin B(1) receptor selective ligand [3H]des-Arg(10)-kallidin, also increased, peaking at 4 h and remaining elevated for 20 h. The B(max) value for [3H]des-Arg(10)-kallidin rose from 280+/-102 fmol/mg (n=3) to 701+/-147 fmol/mg (n=3), but the K(D) value remained unaltered (control, 1.04+/-0.33 nM (n=3); interleukin-1 beta, 0.88+/-0.41 nM (n=3)). The interleukin-1 beta-induced [3H]des-Arg(10)-kallidin binding sites were functional receptors, as bradykinin B(1) receptor agonist-induced responses increased in treated cells. Bradykinin B(2) receptor mRNA and [3H]bradykinin binding were upregulated by interleukin-1 beta, but not TNF-alpha. The effect of interleukin-1 beta on bradykinin B(2) receptors was smaller than for bradykinin B(1) receptors. Cycloheximide prevented interleukin-1 beta-mediated increases in B(1) and B(2) binding, but not mRNA suggesting that de novo synthesis of a transcriptional activator was unnecessary.

  18. Antagonism of bradykinin B2 receptor prevents inflammatory responses in human endothelial cells by quenching the NF-kB pathway activation.

    Directory of Open Access Journals (Sweden)

    Erika Terzuoli

    Full Text Available 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.

  19. 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


    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

  20. 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


    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

  1. Renal and blood pressure phenotype in 18-mo-old bradykinin B2R(-/-)CRD mice. (United States)

    Harrison-Bernard, Lisa M; Dipp, Susana; El-Dahr, Samir S


    Aberrant gene-environment interactions are implicated in the pathogenesis of congenital renal dysgenesis (CRD), a leading cause of renal failure in infants and children. We have recently developed an animal model of CRD that is caused by gestational salt stress (5% NaCl diet; HS) of bradykinin B2R null mice [B2R(-/-)CRD; El-Dahr SS, Harrison-Bernard LM, Dipp S, Yosipiv IV, and Meleg-Smith S. Physiol Genomics 3: 121-131, 2000.]. Developing B2R(-/-)CRD mice exhibit tubular and glomerular cysts, stromal expansion, and loss of corticomedullary differentiation. In addition, B2R(-/-)CRD mice exhibit transient hypertension from 2 to 4 mo of age. The present study was designed to determine the long-term consequences of CRD on renal morphology and salt sensitivity of blood pressure in B2R(-/-)CRD mice. One-year- and 18-mo-old B2R(-/-)CRD mice exhibited stunted renal growth, glomerular cystic abnormalities, and collecting duct ectasia. Moreover, tumors of mesenchymal cell origin emerged in the dysplastic kidneys of 90% of 1-yr-old and 100% of 18-mo-old B2R(-/-)CRD mice but not in age-matched B2R(-/-) or wild-type mice. When challenged with an HS diet, 18-mo-old B2R(-/-)CRD exhibited a significant rise in systolic and diastolic blood pressures and more pronounced natriuresis and diuresis compared with salt-loaded 18-mo-old wild-type mice. Kidney aquaporin-2 expression was decreased by 50%, whereas renin, ANG type 1 receptor, and Na+-K+-ATPase levels were not different in B2R(-/-)CRD mice compared with controls. In conclusion, this study demonstrates that B2R(-/-)CRD mice exhibit permanent phenotypic and functional abnormalities in renal growth and differentiation. This novel model of human disease links gene-environment interactions with renal development and blood pressure homeostasis.

  2. Biotechnological Fluorescent Ligands of the Bradykinin B1 Receptor: Protein Ligands for a Peptide Receptor.

    Directory of Open Access Journals (Sweden)

    Xavier Charest-Morin

    Full Text Available The bradykinin (BK B1 receptor (B1R is a peculiar G protein coupled receptor that is strongly regulated to the point of being inducible in immunopathology. Limited clinical evidence suggests that its expression in peripheral blood mononuclear cells is a biomarker of active inflammatory states. In an effort to develop a novel imaging/diagnostic tool, we report the rational design and testing of a fusion protein that is a ligand of the human B1R but not likely to label peptidases. This ligand is composed of a fluorescent protein (FP (enhanced green FP [EGFP] or mCherry prolonged at its N-terminus by a spacer peptide and a classical peptide agonist or antagonist (des-Arg9-BK, [Leu8]des-Arg9-BK, respectively. The design of the spacer-ligand joint peptide was validated by a competition assay for [3H]Lys-des-Arg9-BK binding to the human B1R applied to 4 synthetic peptides of 18 or 19 residues. The labeling of B1R-expressing cells with EGFP or mCherry fused with 7 of such peptides was performed in parallel (microscopy. Both assays indicated that the best design was FP-(Asn-Glyn-Lys-des-Arg9-BK; n = 15 was superior to n = 5, suggesting benefits from minimizing steric hindrance between the FP and the receptor. Cell labeling concerned mostly plasma membranes and was inhibited by a B1R antagonist. EGFP-(Asn-Gly15-Lys-des-Arg9-BK competed for the binding of [3H]Lys-des-Arg9-BK to human recombinant B1R, being only 10-fold less potent than the unlabeled form of Lys-des-Arg9-BK to do so. The fusion protein did not label HEK 293a cells expressing recombinant human BK B2 receptors or angiotensin converting enzyme. This study identifies a modular C-terminal sequence that can be adapted to protein cargoes, conferring high affinity for the BK B1R, with possible applications in diagnostic cytofluorometry, histology and drug delivery (e.g., in oncology.

  3. Renal Histological Changes and Down-regulation of Bradykinin B2 Receptor mRNA in Rat Remnant Kidney Model%大鼠残肾模型肾脏组织学和缓激肽B2受体mRNA表达的变化

    Institute of Scientific and Technical Information of China (English)

    凃玲; 邓娟娟; 万槐斌; 汪道文


    目的 研究大鼠残肾模型肾脏组织学和缓激肽B2受体(BKB2R)mRNA表达水平的变化.方法 24只雄性Wistar大鼠随机分成模型组和假手术组,每组12只.5/6肾切除术构建大鼠残肾模型.于造模前和造模后15、30、60、120 d分别检测大鼠尾动脉血压和血清肌酐水平.造模后1月和4月分别处死模型组和假手术组大鼠各6只,肾组织石蜡切片、PAS染色观察肾脏组织学改变,RT-real time PCR法检测肾组织BKB2R mRNA的表达水平.结果 模型组大鼠造模后15 d血压和血清肌酐水平即较造模前明显升高(均P<0.01),以后逐渐上升至120 d达高峰;造模后1月残肾已出现肾小球代偿肥大,系膜中度增生,肾组织BKB2R mRNA的表达水平下调,4月时残肾出现明显的肾小球硬化、肾小管坏死和肾间质纤维化,肾组织BKB2R mRNA的表达水平进一步下调(P<0.01).结论 残肾模型大鼠在造模后15d即出现明显的肾功能不全,随后进行性加重,肾组织BKB2R mRNA的表达水平则逐渐下调.

  4. Pharmacologic Targets and Prototype Therapeutics in the Kallikrein-Kinin System: Bradykinin Receptor Agonists or Antagonists

    Directory of Open Access Journals (Sweden)

    J. N. Sharma


    Full Text Available The kallikrein-kinin system (KKS is a complex system produced in various organs. This system includes kininogen (precursor for kinin, kallikreins, and pharmacologically active bradykinin (BK, which is considered to be proinflammatory and/or cardioprotective. It is a proinflammatory polypeptide that is involved in many pathological conditions and can cause pain, inflammation, increased vascular permeability, vasodilation, contraction of various smooth muscles, as well as cell proliferation. On the other hand, it has been shown that BK has cardioprotective effects, as all components of KKS are located in the cardiac muscles. Numerous observations have indicated that decreased activity of this system may lead to cardiovascular diseases, such as hypertension, cardiac failure, and myocardial infarction. BK acts on two receptors, B1 and B2, which are linked physiologically through their natural stimuli and their common participation in a variety of inflammatory responses. Recently, numerous BK antagonists have been developed in order to treat several diseases that are due to excessive BK formation. Although BK has many beneficial effects, it has been recognized to have some undesirable effects that can be reversed with BK antagonists. In addition, products of this system have multiple interactions with other important metabolic pathways, such as the renin-angiotensin system.

  5. Global renal gene expression profiling analysis in B2-kinin receptor null mice: impact of diabetes.

    Directory of Open Access Journals (Sweden)

    Miran A Jaffa

    Full Text Available Diabetic nephropathy (DN, the leading cause of end-stage renal failure, is clinically manifested by albuminuria and a progressive decline in glomerular filtration rate. The risk factors and mechanisms that contribute to the development and progression of DN are still incompletely defined. To address the involvement of bradykinin B(2-receptors (B(2R in DN, we used a genome wide approach to study the effects of diabetes on differential renal gene expression profile in wild type and B(2R knockout (B(2R(-/- mice. Diabetes was induced with streptozotocin and plasma glucose levels and albumin excretion rate (AER were measured at predetermined times throughout the 23 week study period. Longitudinal analysis of AER indicated that diabetic B(2R(-/-D null mice had a significantly decreased AER levels compared to wild type B(2R(+/+D mice (P = 0.0005. Results from the global microarray study comparing gene expression profiles among four groups of mice respectively: (B(2R(+/+C, B(2R(+/+D, B(2R(-/-C and B(2R(-/-D highlighted the role of several altered pathological pathways in response to disruption of B(2R and to the diabetic state that included: endothelial injury, oxidative stress, insulin and lipid metabolism and inflammatory process with a marked alteration in the pro-apoptotic genes. The findings of the present study provide a global genomics view of biomarkers that highlight the mechanisms and putative pathways involved in DN.

  6. Role of kinin B2 receptors in opioid-induced hyperalgesia in inflammatory pain in mice. (United States)

    Grastilleur, Sébastien; Mouledous, Lionel; Bedel, Jerome; Etcheverry, Jonathan; Bader, Michael; Girolami, Jean-Pierre; Fourcade, Olivier; Frances, Bernard; Minville, Vincent


    Postoperative pain management is a clinical challenge that can be complicated by opioid-induced hyperalgesia (OIH). Kinin receptors could mediate both the acute and chronic phases of inflammation and pain. A few recent studies suggest that dynorphin A could maintain neuropathic pain by activating the bradykinin (BK) receptor. Thus, the effect of a single administration of sufentanil (a μ-opioid receptor agonist) was investigated in a model of carrageenan-induced inflammatory pain using three strains of mice, i.e., knockout mice for one kinin receptor, B1R or B2R (B1KO, B2KO), and wild-type C57/BL6J mice (WT) treated with either a B1R (R954) or a B2R antagonist (HOE140) or a KKS inhibitor (aprotinin). Pain was assessed and compared between the different groups using two behavioral tests exploring mechanical (von Frey filaments) and thermal (Hargreaves test) sensitivity. Pretreatment with sufentanil induced a sustained increase in pain sensitivity with a delayed return to baseline values characterizing an OIH in carrageenan-injected mice only. Sufentanil-induced OIH was not observed in B2KO but persisted in B1KO and was blunted by aprotinin and the B2R antagonist only. Collectively, our data indicate that the B2R receptor and BK synthesis or availability are essential peripheral steps in the mechanism leading to OIH in a pain context.

  7. Improvement of skin wound healing in diabetic mice by kinin B2 receptor blockade. (United States)

    Desposito, Dorinne; Chollet, Catherine; Taveau, Christopher; Descamps, Vincent; Alhenc-Gelas, François; Roussel, Ronan; Bouby, Nadine; Waeckel, Ludovic


    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 mice, we assessed the effect of kinin receptor activation or inhibition by subtype-selective pharmacological agonists (B1R and B2R) and antagonist (B2R) on healing of experimental skin wounds. We also studied effects of agonists and antagonist on keratinocytes and fibroblasts in vitro. Levels of Bdkrb1 (encoding B1R) and Bdkrb2 (encoding B2R) mRNAs increased 1-2-fold in healthy and wounded diabetic skin compared with in non-diabetic skin. Diabetes delayed wound healing. The B1R agonist had no effect on wound healing. In contrast, the B2R agonist impaired wound repair in both non-diabetic and diabetic mice, inducing skin disorganization and epidermis thickening. In vitro, B2R activation unbalanced fibroblast/keratinocyte proliferation and increased keratinocyte migration. These effects were abolished by co-administration of B2R antagonist. Interestingly, in the two mouse models of diabetes, the B2R antagonist administered alone normalized wound healing. This effect was associated with the induction of Ccl2 (encoding monocyte chemoattractant protein 1)/Tnf (encoding tumour necrosis factor α) mRNAs. Thus stimulation of kinin B2 receptor impairs skin wound healing in mice. B2R activation occurs in the diabetic skin and delays wound healing. B2R blockade improves skin wound healing in diabetic mice and is a potential therapeutic approach to diabetic ulcers.

  8. Compensatory function of bradykinin B1 receptor in the inhibitory effect of captopril on cardiomyocyte hypertrophy and cardiac fibroblast proliferation in neonatal rats

    Institute of Scientific and Technical Information of China (English)

    ZOU Jun; REN Jiang-hua; FENG Dan; WANG Hong; XU Jiang


    Background Bradykinin(BK)acts mainly on two receptor subtypes:B1 and B2,and activation of B2 receptor mediates the most well-known cardioprotective effects of angiotensin converting enzyme inhibitors(ACEi),however,the role that B1 receptor plays in ACEi has not been fully defined.We examined the role of B1 receptor in the inhibitory effect of ACE inhibitor captopril on rat cardiomyocyte hypertrophy and cardiac fibroblast proliferation induced by angiotensin Ⅱ(Ang Ⅱ) and explored its possible mechanism.Methods Neonatal cardiomyocytes and cardiac fibroblasts(CFs)were randomly treated with Ang Ⅱ,captopril,B2 receptor antagonist(HOE-140)and B1 receptor antagonist(des-Arg10,Leu9-kallidin)alone or in combination.Flow cytometry was used to evaluate cell cycle,size and protein content.Nitric oxide(NO)and intracellular cyclic guanosine monophosphate(cGMP)level were measured by colorimetry and radioimmunoassay.Results After the CFs and cardiomyocytes were incubated with 0.1 μmol/L Ang Ⅱ for 48 hours.the percentage of CFs in the S stage,cardiomyocytes size and protein content significantly increased(both P<0.01 vs control),and these increases were inhibited by 10 μmol/L captopril.However,NO and cGMP levels were significantly higher than that with Ang Ⅱ alone(both P<0.01).1 μmol/L HOE-140 or 0.1 μmol/L des-Arg10,Leu9-kallidin attenuated the effects of captopril,which was blunted further by blockade of both B1 and B2 receptors.Conclusions Acting via B2 receptor,BK contributes to the antihypertrophic and antiproliferative effects of captopril on cardiomyocytes and CFs.In the absence of B2 receptor,B1 receptor may act a compensatory mechanism for the B2 receptor and contribute to the inhibition of cardiomyocyte hypertrophy and CFs proliferation by captopril.NO and cGMP play an important role in the effect of B1 receptor.

  9. 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


    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

  10. 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


    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.

  11. Bradykinin and histamine-induced cytosolic calcium increase in capillary endothelial cells of bovine adrenal medulla. (United States)

    Vinet, Raúl; Cortés, Magdalena P; Alvarez, Rocío; Delpiano, Marco A


    We have assessed the effect of bradykinin and histamine on the cytosolic free calcium concentration ([Ca(2+)]i ) of bovine adrenal medulla capillary endothelial cells (BAMCECs). To measure [Ca(2+)]i changes in BAMCECs the intracellular fluorescent probe, fluo-3 AM, was used. Bradykinin (3 µM) produced a transient monophasic increase in [Ca(2+)]i , which was depressed by B1650 (0.1 µM), a B2-bradykinin receptor antagonist (D-Arg-[Hyp(3), Thi(5,8) , D-Phe(7)]-Bradykinin). Similarly, increase in [Ca(2+)]i induced by histamine was also depressed by tripolidine (0.1 µM), an H1-histamine receptor antagonist. [Ca(2+)]i increase induced by both agonists was unaffected in the absence of extracellular Ca(2+) or presence of antagonists of voltage operated Ca(2+) channels (VOCCs). Thapsigargin (1 µM) did not abolish the increase of [Ca(2+)]i produced by bradykinin, but abolished that of histamine. In contrast, caffeine (100 µM), abolished the [Ca(2+)]i response induced by bradykinin (3 µM), but did not affect the [Ca(2+)]i increase induced by histamine (100 µM). The results indicate the presence of B2 bradykinin- and H1 histamine-receptors in BAMCECs. Liberation of Ca(2+) induced by both agonists occurs through 2 different intracellular mechanisms. While bradykinin activates a sarco(endo) plasmic reticulum (SER) containing a SER Ca(2+) -ATPase (SERCA) thapsigargin-insensitive, histamine activates a SER containing a SERCA thapsigargin-sensitive. We suggest that the increase in [Ca(2+)]i induced by bradykinin and histamine could be of physiological relevance, modulating adrenal gland microcirculation.

  12. Bradykinin and its role in osteoarthritis

    Directory of Open Access Journals (Sweden)

    L. De Falco


    Full Text Available Osteoarthritis (OA, the most common joint disorder, is a disease involving all the articular structures. It presents both degenerative and inflammatory aspects. Recently, the important role of Bradykinin (BK, a phlogistic mediator, has been proposed in the pathophysiology of OA. In our review, we summarized the currently available information on the mechanisms of action of BK in OA by linking its B2 receptors. Then, we analyzed the data about the effects of BK in synoviocytes and chondrocytes cultures. Furthermore, we described the action of B2 receptor antagonists (Icatibant and Fasitibant, presenting them as new promising symptom-anddisease- modifying agents in the treatment of OA. However, more in vitro, animal model and clinical studies, are needed to better understand the mechanisms of action as well as the efficacy and tolerability of the B2 receptor antagonists in OA.

  13. Bradykinin promotes migration and invasion of human immortalized trophoblasts

    Directory of Open Access Journals (Sweden)

    Lisboa Francisco


    Full Text Available Abstract Having demonstrated that the bradykinin B2 receptor (B2R is expressed in cells that participate in trophoblast invasion in humans and guinea-pigs, we investigated the role of bradykinin (BK on cell migration and invasion in the HTR-8/SVneo trophoblast cell line using wound healing and invasion assays. First, we documented that HTR-8/SVneo cells expressed kallikrein, B2R, B1R, MMP-2 and MMP-9 using immunocytochemistry. Incubation with BK (10.0 microMol/L for 18 hours increased the migration index 3-fold in comparison to controls or to cells preincubated with the B2R antagonist HOE-140. BK (10.0 microMol/L incubation yielded a similar number of proliferating and viable cells as controls, therefore the enhanced closure of the wound cannot be attributed to proliferating cells. Incubation with BK (10.0 microMol/L for 18 hours increased the invasion index 2-fold in comparison to controls or to cells preincubated with the antagonist of the B2R. Neither the B1R ligand Lys-des-Arg9 BK, nor its antagonist Lys-(des-Arg9-Leu8, modified migration and invasion. Further support for the stimulatory effect of B2R activation on migration and invasion is provided by the 3-fold increase in the number of filopodia per cell versus controls or cells preincubated with the B2R antagonist. Bradykinin had no effect on the cellular protein content of the B2R, nor the MMP-9 and MMP-2 gelatinase activity in the culture media varied after incubation with BK. This study adds bradykinin-acting on the B2R-to the stimuli of trophoblast migration and invasion, an effect that should be integrated to other modifications of the kallikrein-kinin system in normal and pathological pregnancies.

  14. Bradykinin promotes neuron-generating division of neural progenitor cells through ERK activation. (United States)

    Pillat, Micheli M; Lameu, Claudiana; Trujillo, Cleber A; Glaser, Talita; Cappellari, Angélica R; Negraes, Priscilla D; Battastini, Ana M O; Schwindt, Telma T; Muotri, Alysson R; Ulrich, Henning


    During brain development, cells proliferate, migrate and differentiate in highly accurate patterns. In this context, published results indicate that bradykinin functions in neural fate determination, favoring neurogenesis and migration. However, mechanisms underlying bradykinin function are yet to be explored. Our findings indicate a previously unidentified role for bradykinin action in inducing neuron-generating division in vitro and in vivo, given that bradykinin lengthened the G1-phase of the neural progenitor cells (NPC) cycle and increased TIS21 (also known as PC3 and BTG2) expression in hippocampus from newborn mice. This role, triggered by activation of the kinin-B2 receptor, was conditioned by ERK1/2 activation. Moreover, immunohistochemistry analysis of hippocampal dentate gyrus showed that the percentage of Ki67(+) cells markedly increased in bradykinin-treated mice, and ERK1/2 inhibition affected this neurogenic response. The progress of neurogenesis depended on sustained ERK phosphorylation and resulted in ERK1/2 translocation to the nucleus in NPCs and PC12 cells, changing expression of genes such as Hes1 and Ngn2 (also known as Neurog2). In agreement with the function of ERK in integrating signaling pathways, effects of bradykinin in stimulating neurogenesis were reversed following removal of protein kinase C (PKC)-mediated sustained phosphorylation.

  15. Design, synthesis and evaluation of (18)F-labeled bradykinin B1 receptor-targeting small molecules for PET imaging. (United States)

    Zhang, Zhengxing; Kuo, Hsiou-Ting; Lau, Joseph; Jenni, Silvia; Zhang, Chengcheng; Zeisler, Jutta; Bénard, François; Lin, Kuo-Shyan


    Two fluorine-18 ((18)F) labeled bradykinin B1 receptor (B1R)-targeting small molecules, (18)F-Z02035 and (18)F-Z02165, were synthesized and evaluated for imaging with positron emission tomography (PET). Z02035 and Z02165 were derived from potent antagonists, and showed high binding affinity (0.93±0.44 and 2.80±0.50nM, respectively) to B1R. (18)F-Z02035 and (18)F-Z02165 were prepared by coupling 2-[(18)F]fluoroethyl tosylate with their respective precursors, and were obtained in 10±5 (n=4) and 22±14% (n=3), respectively, decay-corrected radiochemical yield with >99% radiochemical purity. (18)F-Z02035 and (18)F-Z02165 exhibited moderate lipophilicity (LogD7.4=1.10 and 0.59, respectively), and were stable in mouse plasma. PET imaging and biodistribution studies in mice showed that both tracers enabled visualization of the B1R-positive HEK293T::hB1R tumor xenografts with better contrast than control B1R-negative HEK293T tumors. Our data indicate that small molecule antagonists can be used as pharmacophores for the design of B1R-targeting PET tracers.

  16. Icatibant, an inhibitor of bradykinin receptor 2, for hereditary angioedema attacks: prospective experimental single-cohort study

    Directory of Open Access Journals (Sweden)

    Regis Albuquerque Campos

    Full Text Available CONTEXT AND OBJECTIVE: Hereditary angioedema (HAE with C1 inhibitor deficiency manifests as recurrent episodes of edema involving the skin, upper respiratory tract and gastrointestinal tract. It can be lethal due to asphyxia. The aim here was to evaluate the response to therapy for these attacks using icatibant, an inhibitor of the bradykinin receptor, which was recently introduced into Brazil.DESIGN AND SETTING: Prospective experimental single-cohort study on the efficacy and safety of icatibant for HAE patients.METHODS: Patients with a confirmed HAE diagnosis were enrolled according to symptoms and regardless of the time since onset of the attack. Icatibant was administered in accordance with the protocol that has been approved in Brazil. Symptom severity was assessed continuously and adverse events were monitored.RESULTS: 24 attacks in 20 HAE patients were treated (female/male 19:1; 19-55 years; median 29 years of age. The symptoms were: subcutaneous edema (22/24; abdominal pain (15/24 and upper airway obstruction (10/24. The time taken until onset of relief was: 5-10 minutes (5/24; 20.8%; 10-20 (5/24; 20.8%; 20-30 (8/24; 33.4%; 30-60 (5/24; 20.8%; and 2 hours (1/24; 4.3%. The time taken for complete resolution of symptoms ranged from 4.3 to 33.4 hours. Adverse effects were only reported at injection sites. Mild to moderate erythema and/or feelings of burning were reported by 15/24 patients, itching by 3 and no adverse effects in 6.CONCLUSION: HAE type I patients who received icatibant responded promptly; most achieved improved symptom severity within 30 minutes. Local adverse events occurred in 75% of the patients.

  17. ErbB2 resembles an autoinhibited invertebrate epidermal growth factor receptor

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

  18. erbB2 is required for G protein-coupled receptor signaling in the heart


    Negro, Alejandra; Brar, Bhawanjit K.; Gu, Yusu; Peterson, Kirk L.; Vale, Wylie; Lee, Kuo-Fen


    erbB2/Her2, a ligandless receptor kinase, has pleiotropic effects on mammalian development and human disease. The absence of erbB2 signaling in cardiac myocytes results in dilated cardiomyopathy in mice, resembling the cardiotoxic effects observed in a subset of breast cancer patients treated with the anti-Her2 antibody herceptin. Emerging evidence suggests that erbB2 is pivotal for integrating signaling networks involving multiple classes of extracellular signals. However, its role in G prot...

  19. Bradykinin inhibits oxidative stress-induced cardiomyocytes senescence via regulating redox state.

    Directory of Open Access Journals (Sweden)

    Ruolan Dong

    Full Text Available BACKGROUND: Cell senescence is central to a large body of age related pathology, and accordingly, cardiomyocytes senescence is involved in many age related cardiovascular diseases. In consideration of that, delaying cardiomyocytes senescence is of great importance to control clinical cardiovascular diseases. Previous study indicated that bradykinin (BK protected endothelial cells from senescence induced by oxidative stress. However, the effects of bradykinin on cardiomyocytes senescence remain to be elucidated. In this study, we investigated the effect of bradykinin on H2O2-induced H9C2 cells senescence. METHODS AND RESULTS: Bradykinin pretreatment decreased the senescence induced by H2O2 in cultured H9C2 cells in a dose dependent manner. Interestingly, 1 nmol/L of BK almost completely inhibited the increase in senescent cell number and p21 expression induced by H2O2. Since H2O2 induces senescence through superoxide-induced DNA damage, we also observed the DNA damage by comet assay, and BK markedly reduced DNA damage induced by H2O2, and moreover, BK treatment significantly prevented reactive oxygen species (ROS production in H9C2 cells treated with H2O2. Importantly, when co-incubated with bradykinin B2 receptor antagonist HOE-140 or eNOS inhibitor N-methyl-L-arginine acetate salt (L-NAME, the protective effects of bradykinin on H9C2 senescence were totally blocked. Furthermore, BK administration significantly prevented the increase in nicotinamide adenine dinucleotide phosphate (NADPH oxidase activity characterized by increased ROS generation and gp91 expression and increased translocation of p47 and p67 to the membrane and the decrease in superoxide dismutase (SOD activity and expression induced by H2O2 in H9C2 cells, which was dependent on BK B2 receptor mediated nitric oxide (NO release. CONCLUSIONS: Bradykinin, acting through BK B2 receptor induced NO release, upregulated antioxidant Cu/Zn-SOD and Mn-SOD activity and expression while

  20. The relationship of cerb B 2 expression with estrogen receptor and progesterone receptor and prognostic parameters in endometrial carcinomas

    Directory of Open Access Journals (Sweden)

    Kandemir Nilufer


    Full Text Available Abstract Background Endometrial carcinoma (EC is the most common malignancy of the female genital tract. Gene alterations and overexpression of various oncogenes are important in tumor development. The human HER 2 neu (c-erbB-2 gene product is a transmembrane receptor with an intracellular tyrosine kinase that plays an important role in coordinating the endometrial growth factor receptor signaling network. The aim of this study was to investigate the expression of c-erbB-2 in endometrial cancer, to study its correlation to established prognostic parameters and estrogen receptor (ER and progesterone receptor (PR status. Methods Immunohistochemical (IHC analyses of ER, PR and c-erbB-2 were performed in 72 EC cases. Results We detected a positive staining with c erbB 2 in 18.1% of the cases and determined a statistically significant relation between c-erbB-2 and PR. We could not find a statistically significant relation between c-erbB-2 staining and ER. There was not a statistically significant difference between c-erbB-2 and histological grade. The highest level of c-erbB-2 was found in grade 2 cases. There was not any statistically significant relation between c-erbB-2 and menstrual status, myometrial invasion, lymph node status, stage and survival. Conclusions Although our study provides additional evidence of the potential prognostic role of c-erbB-2, further prospective and controlled studies are required to validate their clinical usefulness.

  1. The rat ErbB2 tyrosine kinase receptor produced in plants is immunogenic in mice and confers protective immunity against ErbB2(+) mammary cancer. (United States)

    Matić, Slavica; Quaglino, Elena; Arata, Lucia; Riccardo, Federica; Pegoraro, Mattia; Vallino, Marta; Cavallo, Federica; Noris, Emanuela


    The rat ErbB2 (rErbB2) protein is a 185-kDa glycoprotein belonging to the epidermal growth factor-related proteins (ErbB) of receptor tyrosine kinases. Overexpression and mutations of ErbB proteins lead to several malignancies including breast, lung, pancreatic, bladder and ovary carcinomas. ErbB2 is immunogenic and is an ideal candidate for cancer immunotherapy. We investigated the possibility of expressing the extracellular (EC) domain of rErbB2 (653 amino acids, aa) in Nicotiana benthamiana plants, testing the influence of the 23 aa transmembrane (TM) sequence on protein accumulation. Synthetic variants of the rErbB2 gene portion encoding the EC domain, optimized with a human codon usage and either linked to the full TM domain (rErbB2_TM, 676 aa), to a portion of it (rErbB2-pTM, 662 aa), or deprived of it (rErbB2_noTM, 653 aa) were cloned in the pEAQ-HT expression vector as 6X His tag fusions. All rErbB2 variants (72-74.5 kDa) were transiently expressed, but the TM was detrimental for rErbB2 EC accumulation. rERbB2_noTM was the most expressed protein; it was solubilized and purified with Nickel affinity resin. When crude soluble extracts expressing rErbB2_noTM were administered to BALB/c mice, specific rErbB2 immune responses were triggered. A potent antitumour activity was induced when vaccinated mice were challenged with syngeneic transplantable ErbB2(+) mammary carcinoma cells. To our knowledge, this is the first report of expression of rErbB2 in plants and of its efficacy in inducing a protective antitumour immune response, opening interesting perspectives for further immunological testing.

  2. Ex Vivo Smooth Muscle Pharmacological Effects of a Novel Bradykinin-Related Peptide, and Its Analogue, from Chinese Large Odorous Frog, Odorrana livida Skin Secretions (United States)

    Xiang, Jie; Wang, Hui; Ma, Chengbang; Zhou, Mei; Wu, Yuxin; Wang, Lei; Guo, Shaodong; Chen, Tianbao; Shaw, Chris


    Bradykinin-related peptides (BRPs) are one of the most extensively studied frog secretions-derived peptide families identified from many amphibian species. The diverse primary structures of BRPs have been proven essential for providing valuable information in understanding basic mechanisms associated with drug modification. Here, we isolated, identified and characterized a dodeca-BRP (RAP-L1, T6-BK), with primary structure RAPLPPGFTPFR, from the skin secretions of Chinese large odorous frogs, Odorrana livida. This novel peptide exhibited a dose-dependent contractile property on rat bladder and rat ileum, and increased the contraction frequency on rat uterus ex vivo smooth muscle preparations; it also showed vasorelaxant activity on rat tail artery smooth muscle. In addition, the analogue RAP-L1, T6, L8-BK completely abolished these effects on selected rat smooth muscle tissues, whilst it showed inhibition effect on bradykinin-induced rat tail artery relaxation. By using canonical antagonist for bradykinin B1 or B2 type receptors, we found that RAP-L1, T6-BK -induced relaxation of the arterial smooth muscle was very likely to be modulated by B2 receptors. The analogue RAP-L1, T6, L8-BK further enhanced the bradykinin inhibitory activity only under the condition of co-administration with HOE140 on rat tail artery, suggesting a synergistic inhibition mechanism by which targeting B2 type receptors. PMID:27690099

  3. Mapping of the human bradikinin B2 receptor gene and GALC gene at 14q31-32.1, the region of the Machado Joseph disease locus

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, V.T.T.; Cox, D.W. [Hospital for Sick Children, Toronto (Canada)]|[Univ. of Toronto (Canada)


    Bradykinin is a nine amino acid peptide liberated from the {alpha}2 globulin, kininogen, during inflammatory responses. Substantial evidence shows that bradikinin is involved in human inflammatory disorders. There are two types of kinin receptors: B1 and B2. The human bradikinin B2 receptor (BKRB2) gene was previously localized to chromosome 14 by somatic cell hybrids. Krabbe disease is an autosomal recessive disorder caused by deficiency of galactocerebrosidase (GALC). GALC has been previously localized to chromosome 14 at q31 by in situ hybridization. We have further defined the localization of the BKRB2 and GALC genes by physical and genetic linkage mapping. Primers were designed from the 3{prime} untranslated region of each gene. PCR was performed on human/rodent somatic cell hybrid carrying portions of chromosome 14, and on flow sorted chromosome DNA of patients with a deletion or translocation on chromosome 14. Results place the two genes between D14S48 and Pl, the same region as the Machado Joseph disease (MJD) gene. The genomic chromosome 14-specific cosmid library (DOE, Los Alamos) was screened using PCR products obtained from both sets of primers as probes. Positive clones for each gene were screened for di, tri and tetranucleotide repeats. A polymorphic CA repeat marker was obtained from the BKRB2 clones. CEPH families which show recombinants between D14S48 and Pl were typed with this marker and other published markers, which we have mapped in the region: D14S140, D14S68, D14S73, D14S67, D14S256 and D14S81. This positions BDRB2 more precisely and also provides an important map for further localization of the MJD gene.

  4. MRP transporters as membrane machinery in the bradykinin-inducible export of ATP. (United States)

    Zhao, Yumei; Migita, Keisuke; Sun, Jing; Katsuragi, Takeshi


    Adenosine triphosphate (ATP) plays the role of an autocrine/paracrine signal molecule in a variety of cells. So far, however, the membrane machinery in the export of intracellular ATP remains poorly understood. Activation of B2-receptor with bradykinin-induced massive release of ATP from cultured taenia coli smooth muscle cells. The evoked release of ATP was unaffected by gap junction hemichannel blockers, such as 18alpha-glycyrrhetinic acid and Gap 26. Furthermore, the cystic fibrosis transmembrane regulator (CFTR) coupled Cl(-) channel blockers, CFTR(inh)172, 5-nitro-2-(3-phenylpropylamino)-benzoic acid, Gd3(+) and glibenclamide, failed to suppress the export of ATP by bradykinin. On the other, the evoked release of ATP was greatly reduced by multidrug resistance protein (MRP) transporter inhibitors, MK-571, indomethacin, and benzbromarone. From western blotting analysis, blots of MRP 1 protein only, but not MRP 2 and MRP 3 protein, appeared at 190 kD. However, the MRP 1 protein expression was not enhanced after loading with 1 muM bradykinin for 5 min. Likewise, niflumic acid and fulfenamic acid, Ca2(+)-activated Cl(-) channel blockers, largely abated the evoked release of ATP. The possibility that the MRP transporter system couples with Ca2(+)-activated Cl(-) channel activities is discussed here. These findings suggest that MRP transporters, probably MRP 1, unlike CFTR-Cl(-) channels and gap junction hemichannels, may contribute as membrane machinery to the export of ATP induced by G-protein-coupled receptor stimulation.

  5. Deletion of Kinin B2 Receptor Alters Muscle Metabolism and Exercise Performance.

    Directory of Open Access Journals (Sweden)

    Felipe C G Reis

    Full Text Available Metabolic syndrome is a cluster of metabolic risk factors such as obesity, diabetes and cardiovascular diseases. Mitochondria is the main site of ATP production and its dysfunction leads to decreased oxidative phosphorylation, resulting in lipid accumulation and insulin resistance. Our group has demonstrated that kinins can modulate glucose and lipid metabolism as well as skeletal muscle mass. By using B2 receptor knockout mice (B2R-/- we investigated whether kinin action affects weight gain and physical performance of the animals. Our results show that B2R-/- mice are resistant to high fat diet-induced obesity, have higher glucose tolerance as well as increased mitochondrial mass. These features are accompanied by higher energy expenditure and a lower feed efficiency associated with an increase in the proportion of type I fibers and intermediary fibers characterized by higher mitochondrial content and increased expression of genes related to oxidative metabolism. Additionally, the increased percentage of oxidative skeletal muscle fibers and mitochondrial apparatus in B2R-/- mice is coupled with a higher aerobic exercise performance. Taken together, our data give support to the involvement of kinins in skeletal muscle fiber type distribution and muscle metabolism, which ultimately protects against fat-induced obesity and improves aerobic exercise performance.

  6. Distinct ErbB2 receptor populations differentially interact with beta1 integrin in breast cancer cell models (United States)

    Toscani, Andrés Martín; Sampayo, Rocío G.; Barabas, Federico Martín; Fuentes, Federico; Simian, Marina


    ErbB2 is a member of the ErbB family of tyrosine kinase receptors that plays a major role in breast cancer progression. Located at the plasma membrane, ErbB2 forms large clusters in spite of the presence of growth factors. Beta1 integrin, membrane receptor of extracellular matrix proteins, regulates adhesion, migration and invasiveness of breast cancer cells. Physical interaction between beta1 integrin and ErbB2 has been suggested although published data are contradictory. The aim of the present work was to study the interaction between ErbB2 and beta1 integrin in different scenarios of expression and activation. We determined that beta1 integrin and ErbB2 colocalization is dependent on the expression level of both receptors exclusively in adherent cells. In suspension cells, lack of focal adhesions leave integrins free to diffuse on the plasma membrane and interact with ErbB2 even at low expression levels of both receptors. In adherent cells, high expression of beta1 integrin leaves unbound receptors outside focal complexes that diffuse within the plasma membrane and interact with ErbB2 membrane domains. Superresolution imaging showed the existence of two distinct populations of ErbB2: a major population located in large clusters and a minor population outside these structures. Upon ErbB2 overexpression, receptors outside large clusters can freely diffuse at the membrane and interact with integrins. These results reveal how expression levels of beta1 integrin and ErbB2 determine their frequency of colocalization and show that extracellular matrix proteins shape membrane clusters distribution, regulating ErbB2 and beta1 integrin activity in breast cancer cells. PMID:28306722

  7. GABA(B2) is essential for g-protein coupling of the GABA(B) receptor heterodimer. (United States)

    Robbins, M J; Calver, A R; Filippov, A K; Hirst, W D; Russell, R B; Wood, M D; Nasir, S; Couve, A; Brown, D A; Moss, S J; Pangalos, M N


    GABA(B) receptors are unique among G-protein-coupled receptors (GPCRs) in their requirement for heterodimerization between two homologous subunits, GABA(B1) and GABA(B2), for functional expression. Whereas GABA(B1) is capable of binding receptor agonists and antagonists, the role of each GABA(B) subunit in receptor signaling is unknown. Here we identified amino acid residues within the second intracellular domain of GABA(B2) that are critical for the coupling of GABA(B) receptor heterodimers to their downstream effector systems. Our results provide strong evidence for a functional role of the GABA(B2) subunit in G-protein coupling of the GABA(B) receptor heterodimer. In addition, they provide evidence for a novel "sequential" GPCR signaling mechanism in which ligand binding to one heterodimer subunit can induce signal transduction through the second partner of a heteromeric complex.

  8. Two new bradykinin-related peptides from the venom of the social wasp Protopolybia exigua (Saussure). (United States)

    Mendes, Maria Anita; Palma, Mario Sergio


    Two bradykinin-related peptides (Protopolybiakinin-I and Protopolybiakinin-II) were isolated from the venom of the social wasp Protopolybia exigua by RP-HPLC, and sequenced by Edman degradation method. Peptide sequences of Protopolybiakinin-I and Protopolybiakinin-II were DKNKKPIRVGGRRPPGFTR-OH and DKNKKPIWMAGFPGFTPIR-OH, respectively. Synthetic peptides with identical sequences to the bradykinin-related peptides and their biological functions were characterized. Protopolybiakinin-I caused less potent constriction of the isolated rat ileum muscles than bradykinin (BK). In addition, it caused degranulation of mast cells which was seven times more potent than BK. This peptide causes algesic effects due to the direct activation of B(2)-receptors. Protopolybiakinin-II is not an agonist of rat ileum muscle and had no algesic effects. However, Protopolybiakinin-II was found to be 10 times more potent as a mast cell degranulator than BK. The amino acid sequence of Protopolybiakinin-I is the longest among the known wasp kinins.

  9. Kinin B1 and B2 receptors are overexpressed in the hippocampus of humans with temporal lobe epilepsy. (United States)

    Perosa, Sandra Regina; Argañaraz, Gustavo Adolfo; Goto, Eduardo Massatoshi; Costa, Luciana Gilbert Pessoa; Konno, Ana Carla; Varella, Pedro Paulo Vasconcellos; Santiago, Joselita Ferreira Carvalho; Pesquero, João Bosco; Canzian, Mauro; Amado, Debora; Yacubian, Elza Marcia; Carrete, Henrique; Centeno, Ricardo Silva; Cavalheiro, Esper Abrão; Silva, Jose Antonio; Mazzacoratti, Maria da Graça Naffah


    Molecular biology tools have been employed to investigate the participation of peptides in human temporal lobe epilepsy (TLE). Active polypeptides and their receptors have been related to several brain processes, such as inflammation, apoptosis, brain development, K(+) and Ca(2+) channels' activation, cellular growth, and induction of neuronal differentiation. Previous works have shown a neuroprotector effect for kinin B2 receptor and a deleterious, pro-epileptogenic action for kinin B1 receptor in animal models of TLE. The present work was delineated to analyze the kinin B1 and B2 receptors expression in the hippocampus of patients presenting refractory mesial TLE. The hippocampi were removed during the patients surgery in a procedure used for seizure control and compared with tissues obtained after autopsy. Nissl staining was performed to study the tissue morphology and immunohistochemistry, and Western blot was used to compare the distribution and levels of both receptors in the hippocampus. In addition, real time PCR was employed to analyze the gene expression of these receptors. Nissl staining showed sclerotic hippocampi with hilar, granular, and pyramidal cell loss in TLE patients. Immunohistochemistry and Western blot analyses showed increased expression of kinin B1 and B2 receptors but the real-time PCR data demonstrated increased mRNA level only for kinin B2 receptors, when compared with controls. These data show for the first time a relationship between human TLE and the kallikrein-kinin system, confirming ours previous results, obtained from experimental models of epilepsy.

  10. The mechanism of action of two bradykinin-potentiating peptides on isolated smooth muscle. (United States)

    Ufkes, J G; Aarsen, P N; van der Meer, C


    Bradykinin-induced contractions in the guinea-pig ileum were potentiated by the peptides A-VI-5 (Val-Glu-Ser-Ser-Lys) and BPP5a (Pyr-Lys-Trp-Ala-Pro), while the contractions induced by other agonists were not affected. Neither peptide added alone caused any response. Previous addition of the peptides shortened the latent period following the addition of bradykinin to a value corresponding to the contraction height with an equivalent dose of bradykinin added alone. Bradykinin in contact with a piece of ileum was inactivated at a relatively slow rate. This inactivation was not inhibited by either A-VI-5 or BPP5a in doses causing potentiation. Suppression of the cholinergic activity by cooling, atropine, morphine or tetrodotoxin did not influence the potentiating activity. Addition of the peptides at the moment a submaximal contraction due to bradykinin had been fully established, increased the contraction height within seconds. The two peptides caused a parallel shift to the left of the dose-effect curve of bradykinin, whereas the maximum bradykinin effect remained unchanged. It is concluded that sensitization of bradykinin receptors due to an increased affinity of the receptor for bradykinin is the hypothesis which best fits the experimental findings.

  11. Modulation of bradykinin-induced gastric-cardiovascular reflexes by histamine. (United States)

    Stebbins, C L; Stahl, G L; Theodossy, S J; Longhurst, J C


    Both histamine and bradykinin induce gastric-cardiovascular reflexes and are released during several pathophysiological conditions. This study examined the possibility that histamine modulates the magnitude of the reflex response to stimulation by bradykinin. Thus in chloralose anesthetized cats, the cardiovascular response to stimulation of the gastric serosa with 1 microgram/ml bradykinin was monitored before and after topical application of 100 micrograms/ml histamine (n = 6) or 1 mg/ml diphenhydramine (H1-receptor antagonist) and histamine (n = 5). After application of histamine, bradykinin-induced increases in mean arterial pressure and left ventricular pressure were attenuated by 23 and 27%, respectively. Conversely, when the H1-receptors on the serosal surface of the stomach were blocked (n = 5) before application of histamine, the pressor response to bradykinin was augmented by 26%. To determine the afferents that might contribute to the attenuating effect of histamine, we recorded single unit activity in 14 A delta and 21 C visceral afferent fibers in response to bradykinin stimulation before and after histamine stimulation. We observed that the impulse activity of 10 of the A delta and 14 of the C fibers to bradykinin stimulation was reduced after treatment with histamine. These results suggest that histamine induces an inhibitory effect on the nerve endings of visceral A delta and C fibers to the action of bradykinin through an H1-receptor mechanism. This inhibitory effect attenuates the magnitude of the consequent cardiovascular reflex response.

  12. Role of non-nitric oxide non-prostaglandin endothelium-derived relaxing factor(s in bradykinin vasodilation

    Directory of Open Access Journals (Sweden)

    A.C. Resende


    Full Text Available The most conspicuous effect of bradykinin following its administration into the systemic circulation is a transient hypotension due to vasodilation. In the present study most of the available evidence regarding the mechanisms involved in bradykinin-induced arterial vasodilation is reviewed. It has become firmly established that in most species vasodilation in response to bradykinin is mediated by the release of endothelial relaxing factors following the activation of B2-receptors. Although in some cases the action of bradykinin is entirely mediated by the endothelial release of nitric oxide (NO and/or prostacyclin (PGI2, a large amount of evidence has been accumulated during the last 10 years indicating that a non-NO/PGI2 factor accounts for bradykinin-induced vasodilation in a wide variety of perfused vascular beds and isolated small arteries from several species including humans. Since the effect of the non-NO/PGI2 endothelium-derived relaxing factor is practically abolished by disrupting the K+ electrochemical gradient together with the fact that bradykinin causes endothelium-dependent hyperpolarization of vascular smooth muscle cells, the action of such factor has been attributed to the opening of K+ channels in these cells. The pharmacological characteristics of these channels are not uniform among the different blood vessels in which they have been examined. Although there is some evidence indicating a role for KCa or KV channels, our findings in the mesenteric bed together with other reports indicate that the K+ channels involved do not correspond exactly to any of those already described. In addition, the chemical identity of such hyperpolarizing factor is still a matter of controversy. The postulated main contenders are epoxyeicosatrienoic acids or endocannabinoid agonists for the CB1-receptors. Based on the available reports and on data from our laboratory in the rat mesenteric bed, we conclude that the NO/PGI2-independent endothelium

  13. Bradykinin may be involved in neuropeptide Y-induced diuresis, natriuresis, and calciuresis. (United States)

    Bischoff, A; Rascher, W; Michel, M C


    Neuropeptide Y (NPY) can cause diuresis, natriuresis, and calciuresis in rats independently of the pressure-natriuresis mechanism (A. Bischoff and M. C. Michel. Pflügers Arch. 435: 443-453, 1998). Because this is seen in systemic but not intrarenal NPY infusion, we have investigated the possible mediator of tubular NPY effects in anesthetized rats. In the present study, infusion of NPY (2 micrograms . kg-1 . min-1) enhanced renovascular resistance by approximately 8 mmHg . ml-1 . min and enhanced urine and sodium excretion by approximately 450 microliter/15 min and approximately 60-85 micromol/15 min, respectively. Acute renal denervation did not alter renovascular or tubular NPY effects, indicating that a neuronally released mediator is not involved. Treatment with the angiotensin II-receptor antagonist losartan prevented the decline of the renovascular response with time but did not modify tubular NPY effects. The bradykinin B2-receptor antagonist icatibant accelerated the decline of the renovascular NPY effects with time; concomitantly, it attenuated NPY-induced diuresis and natriuresis and abolished NPY-induced calciuresis. The converting-enzyme inhibitor ramiprilat prevented the decline of the renovascular response with time; concomitantly, it magnified the NPY-induced diuresis, natriuresis, and calciuresis. We conclude that bradykinin may be involved in NPY-induced diuresis, natriuresis, and, in particular, calciuresis.

  14. Involvement of 5-HT(2A/2B/2C) receptors on memory formation: simple agonism, antagonism, or inverse agonism? (United States)

    Meneses, Alfredo


    1. The 5-HT2 receptors subdivision into the 5-HT(2A/2B/2C) subtypes along with the advent of the selective antagonists has allowed a more detailed investigation on the role and therapeutic significance of these subtypes in cognitive functions. The present study further analyzed the 5-HT2 receptors role on memory consolidation. 2. The SB-200646 (a selective 5-HT(2B/2C) receptor antagonist) and LY215840 (a nonselective 5-HT(2/7) receptor antagonist) posttraining administration had no effect on an autoshaped memory consolidation. However, both drugs significantly and differentially antagonized the memory impairments induced by 1-(3-chlorophenyl)piperazine (mCPP), 1-naphtyl-piperazine (1-NP), mesulergine, or N-(3-trifluoromethylphenyl) piperazine (TFMPP). 3. In contrast, SB-200646 failed to modify the facilitatory procognitive effect produced by (+/-)-2.5-dimethoxy-4-iodoamphetamine (DOI) or ketanserin, which were sensitive to MDL100907 (a selective 5-HT2A receptor antagonist) and to a LY215840 high dose. 4. Finally, SB-200646 reversed the learning deficit induced by dizocilpine, but not that by scopolamine: while SB-200646 and MDL100907 coadministration reversed memory deficits induced by both drugs. 5. It is suggested that 5-HT(2B/2C) receptors might be involved on memory formation probably mediating a suppressive or constraining action. Whether the drug-induced memory impairments in this study are explained by simple agonism, antagonism, or inverse agonism at 5-HT2 receptors remains unclear at this time. 6. Notably, the 5-HT2 receptor subtypes blockade may provide some benefit to reverse poor memory consolidation conditions associated with decreasedcholinergic, glutamatergic, and/or serotonergic neurotransmission.

  15. HER2/ErbB2 receptor signaling in rat and human prolactinoma cells: strategy for targeted prolactinoma therapy. (United States)

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


    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 generated constitutively active HER2-stable GH3 cell transfectants (HER2CA). PRL mRNA levels were induced approximately 250-fold and PRL secretion was enhanced 100-fold in HER2CA cells, which also exhibited increased proliferation. Lapatinib, a dual tyrosine kinase inhibitor (TKI) of both epidermal growth factor receptor (EGFR)/ErbB1 and HER2, blocked receptor signaling, and suppressed PRL expression more than gefitinib, a TKI of EGFR/ErbB1. Lapatinib also suppressed colony formation in soft agar more than gefitinib. Oral lapatinib treatment caused tumor shrinkage and serum PRL suppression both in HER2CA transfectant-inoculated Wistar-Furth rats and in estrogen-induced Fischer344 rat prolactinomas. In cultured human cells derived from resected prolactinoma tissue, lapatinib suppressed both PRL mRNA expression and secretion. These results demonstrate that prolactinoma HER2 potently induces PRL and regulates experimental prolactinoma cell proliferation. Because pituitary HER2 signaling is abrogated by TKIs, this receptor could be an effective target for prolactinoma therapy.

  16. Interaction between V-ATPase B2 and (Pro) renin Receptors in Promoting the progression of Renal Tubulointerstitial Fibrosis. (United States)

    Liu, Yun; Zuo, Sujun; Li, Xiaoyan; Fan, Jinjin; Cao, Xueqin; Yu, Xueqing; Yang, Qiongqiong


    To investigate the levels of (Pro) renin receptor [(P) RR], α-smooth muscle actin (α-SMA), fibronectin (FN), and vacuolar H(+)-ATPase (V-ATPase) subunits (B2, E, and c) in rat unilateral ureteral obstruction (UUO) models and rat proximal tubular epithelial cells (NRK-52E) treated with prorenin to elucidate the role of V-ATPase in these processes by activating the (P) RR. UUO significantly upregulated (P) RR, V-ATPase subunits, α-SMA and FN expression in tubulointerstitium or tubular epithelial cells. A marked colocalization of (P) RR and the B2 subunit was also observed. Prorenin treatment upregulated α-SMA, FN, (P) RR, and V-ATPase subunits and activity in NRK52E cell in a dose- and time-dependent manner. The V-ATPase inhibitor bafilomycin A1 partially blocked prorenin-induced (P) RR, FN, and α-SMA expression. Co-immunoprecipitate and immunofluorescence results demonstrated that the V-ATPase B2 subunit bound to the (P) RR, which was upregulated after prorenin stimulation. Either siRNA-mediated (P) RR or B2 subunit knockdown partially reduced V-ATPase activity and attenuated prorenin-induced FN and α-SMA expression. From the data we can assume that activation of (P) RR and V-ATPase may play an important role in tubulointerstitial fibrosis with possible involvement of interaction of V-ATPase B2 subunit and (P)RR.

  17. Transactivation of EGF receptor and ErbB2 protects intestinal epithelial cells from TNF-induced apoptosis. (United States)

    Yamaoka, Toshimitsu; Yan, Fang; Cao, Hanwei; Hobbs, Stuart S; Dise, Rebecca S; Tong, Wei; Polk, D Brent


    TNF is a pleiotropic cytokine that activates both anti- and proapoptotic signaling pathways, with cell fate determined by the balance between these two pathways. Activation of ErbB family members, including EGF receptor (EGFR/ErbB1), promotes cell survival and regulates several signals that overlap with those stimulated by TNF. This study was undertaken to determine the effects of TNF on EGFR and ErbB2 activation and intestinal epithelial cell survival. Mice, young adult mouse colon epithelial cells, and EGFR knockout mouse colon epithelial cells were treated with TNF. Activation of EGFR, ErbB2, Akt, Src, and apoptosis were determined in vivo and in vitro. TNF stimulated EGFR phosphorylation in young adult mouse colon epithelial cells, and loss of EGFR expression or inhibition of kinase activity increased TNF-induced apoptosis, which was prevented in WT but not by kinase-inactive EGFR expression. Similarly, TNF injection stimulated apoptosis in EGFR-kinase-defective mice (EGFR(wa2)) compared with WT mice. TNF also activated ErbB2, and loss of ErbB2 expression increased TNF-induced apoptosis. Furthermore, Src-kinase activity and the expression of both EGFR and ErbB2 were required for TNF-induced cell survival. Akt was shown to be a downstream target of TNF-activated EGFR and ErbB2. These findings demonstrate that EGFR and ErbB2 are critical mediators of TNF-regulated antiapoptotic signals in intestinal epithelial cells. Given evidence for TNF signaling in the development of colitis-associated carcinoma, this observation has significant implications for understanding the role of EGFR in maintaining intestinal epithelial cell homeostasis during cytokine-mediated inflammatory responses.

  18. Tumor Suppressor Activity of the EphB2 Receptor in Prostate Cancer (United States)


    even cell death (1,57). Both EphB4 and ephrin-B2 are expressed in mouse undifferentiated embryonic stem cells and in early embryoid bodies derived by...towards endothelial and hematopoietic cell lineages (58,59). When embryoid bodies are used to generate hemangioblast cells in vitro, mimicking...developmental events occurring in the blood islands of the yolk sac, EphB4-deficient embryoid bodies display defects in hemangioblast development (58). EphB4

  19. 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

  20. 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


    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.

  1. Elucidating the Role of Truncated ErB2 Receptor (p95) in Breast Cancer (United States)


    to reduce the expression of cell membrane bound p95;5 (ii) a gamma secretase inhibitor that blocked ErbB4 truncation;6 (iii) a calpain I inhibitor...inhibitor of the 20S subunit of the proteasome blocked p95L induction in lapatinib-treated ErbB2+ breast cancer cells. Similarly, MG132 and the calpain ...No independent authentication of these cells was done by the authors. Anti-phosphotyrosine (p-tyr) antibody, GW2974, and calpain inhibitor 1 were

  2. A Functionally Significant Cross-talk between Androgen Receptor and ErbB2 Pathways in Estrogen Receptor Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Ali Naderi


    Full Text Available Recent studies have identified novel subgroups in ER-negative breast cancer based on the expression pattern of androgen receptor (AR. One subtype (molecular apocrine has an over-expression of steroid-response genes and ErbB2. Using breast cancer cell lines with molecular apocrine features, we demonstrate a functional cross-talk between AR and ErbB2 pathways. We show that stimulation of AR and ErbB2 pathways leads to the cross-regulation of gene expression for AR, ErbB2, FOXA1, XBP1, TFF3, and KLK3. As opposed to the physiologic transient phosphorylation of extracellular signal–regulated kinase (ERK1/2 observed with the testosterone treatment, we demonstrate that the addition of ErbB2 inhibition leads to a persistent phosphorylation of ERK1/2, which negatively regulates the downstream signaling and cell growth. This suggests a mechanism for the cross-talk involving the ERK pathway. Moreover, testosterone stimulates the proliferation of molecular apocrine breast cell lines, and this effect can be reversed using antiandrogen flutamide and anti-ErbB2 AG825. Conversely, the growth stimulatory effect of heregulin can also be inhibited with flutamide, suggesting a cross-talk between the AR and ErbB2 pathways affecting cell proliferation. Importantly, there is a synergy with the combined use of flutamide and AG825 on cell proliferation and apoptosis, which indicates a therapeutic advantage in the combined blockage of AR and ErbB2 pathways.

  3. A functionally significant cross-talk between androgen receptor and ErbB2 pathways in estrogen receptor negative breast cancer. (United States)

    Naderi, Ali; Hughes-Davies, Luke


    Recent studies have identified novel subgroups in ER-negative breast cancer based on the expression pattern of androgen receptor (AR). One subtype (molecular apocrine) has an over-expression of steroid-response genes and ErbB2. Using breast cancer cell lines with molecular apocrine features, we demonstrate a functional cross-talk between AR and ErbB2 pathways. We show that stimulation of AR and ErbB2 pathways leads to the cross-regulation of gene expression for AR, ErbB2, FOXA1, XBP1, TFF3, and KLK3. As opposed to the physiologic transient phosphorylation of extracellular signal-regulated kinase (ERK1/2) observed with the testosterone treatment, we demonstrate that the addition of ErbB2 inhibition leads to a persistent phosphorylation of ERK1/2, which negatively regulates the downstream signaling and cell growth. This suggests a mechanism for the cross-talk involving the ERK pathway. Moreover, testosterone stimulates the proliferation of molecular apocrine breast cell lines, and this effect can be reversed using antiandrogen flutamide and anti-ErbB2 AG825. Conversely, the growth stimulatory effect of heregulin can also be inhibited with flutamide, suggesting a cross-talk between the AR and ErbB2 pathways affecting cell proliferation. Importantly, there is a synergy with the combined use of flutamide and AG825 on cell proliferation and apoptosis, which indicates a therapeutic advantage in the combined blockage of AR and ErbB2 pathways.

  4. Aberrant activation of the androgen receptor by NF-kappaB2/p52 in prostate cancer cells. (United States)

    Nadiminty, Nagalakshmi; Lou, Wei; Sun, Meng; Chen, Jun; Yue, Jiao; Kung, Hsing-Jien; Evans, Christopher P; Zhou, Qinghua; Gao, Allen C


    Prostate cancer initiation and progression are uniquely dependent on the androgen receptor (AR). Even when the cancer progresses to a castration-resistant stage, AR signaling remains active via a variety of mechanisms. In the present study, we showed that NF-kappaB/p52 can activate the AR, resulting in increased transactivation of AR-responsive genes, such as PSA and NKX3.1, in a ligand-independent manner. NF-kappaB2/p52 enhances nuclear translocation and activation of AR by interacting with its NH(2)-terminal domain and enhances the recruitment of coactivators such as p300 to the promoters of AR-dependent genes. These results were confirmed in three different prostate cancer cell lines: LAPC-4 (wild-type AR), LNCaP (mutant AR), and C4-2 (castration resistant). Transfection of p52 into LAPC-4 and LNCaP cells (which express low levels of p52) showed increased activation of the endogenous AR. Downregulation of endogenous p52 in C4-2 cells resulted in abrogation of AR constitutive activation. Comparison of the relative effects of p52 and p65 (RelA) showed that p52, but not p65, could activate the AR. Collectively, these findings, together with previous reports that the levels of NF-kappaB2/p52 are elevated in prostate cancer cells and that active NF-kappaB2/p52 promotes prostate cancer cell growth in vitro and in vivo, suggest that NF-kappaB2/p52 may play a critical role in the progression of castration-resistant prostate cancer.

  5. Scavenger receptor b2 as a receptor for hand, foot, and mouth disease and severe neurological diseases. (United States)

    Yamayoshi, Seiya; Fujii, Ken; Koike, Satoshi


    Enterovirus 71 (EV71) is one of the major causative agents of hand, foot, and mouth disease (HFMD). Infection with EV71 is occasionally associated with severe neurological diseases such as acute encephalitis, acute flaccid paralysis, and cardiopulmonary failure. Because cellular receptors for viruses play an important role in cell, tissue, and species tropism, it is important to identify and characterize the receptor molecule. Recently, cellular receptors and host factors that stimulate EV71 infection have been identified. Several lines of evidence suggest that scavenger receptor class B, member 2 (SCARB2) plays critical roles in efficient EV71 infection and the development of disease in humans. In this review, we will summarize the findings of recent studies on EV71 infection and on the roles of SCARB2.

  6. Multiple bradykinin-related peptides from the capture web of the spider Nephila clavipes (Araneae, Tetragnatidae). (United States)

    Volsi, Evelyn C F R; Mendes, Maria Anita; Marques, Maurício Ribeiro; dos Santos, Lucilene Delazari; Santos, Keity Souza; de Souza, Bibiana Monson; Babieri, Eduardo Feltran; Palma, Mario Sergio


    Three bradykinin-related peptides (nephilakinins-I to -III) and bradykinin itself were isolated from the aqueous washing extract of the capture web of the spider Nephila clavipes by gel permeation chromatography on a Sephacryl S-100 column, followed by chromatography in a Hi-Trap Sephadex-G25 Superfine column. The novel peptides occurred in low concentrations and were sequenced through ESI-MS/MS analysis: nephilakinin-I (G-P-N-P-G-F-S-P-F-R-NH2), nephilakinin-II (E-A-P-P-G-F-S-P-F-R-NH2) and nephilakinin-III (P-S-P-P-G-F-S-P-F-R-NH2). Synthetic peptides replicated the novel bradykinin-related peptides, which were submitted to biological characterizations. Nephilakinins were shown to cause constriction on isolated rat ileum preparations and relaxation on rat duodenum muscle preparations at amounts higher than bradykinin; apparently these peptides constitute B2-type agonists of ileal and duodenal smooth muscles. All peptides including the bradykinin were moderately lethal to honeybees. These bradykinin peptides may be related to the predation of insects by the webs of N. clavipes.

  7. Egf binding to its receptor triggers a rapid tyrosine phosphorylation of the erbB-2 protein in the mammary tumor cell line SK-BR-3.


    King, C. R.; Borrello, I; Bellot, F; Comoglio, P; Schlessinger, J


    The epidermal growth factor receptor (EGF-R) and the erbB-2 proto-oncogene product protein are closely related by their structural homology and their shared enzymatic activity as autophosphorylating tyrosine kinases. We show that in mammary tumor cells (SK-BR-3) EGF causes a rapid increase in tyrosine phosphorylation of the erbB-2 protein. Phosphorylation of erbB-2 does not occur in cells lacking the EGF-R (MDA-MB-453). Phosphorylation of erbB-2 in SK-BR-3 cells is blocked if EGF is prevented...

  8. The expression of GABA(B1) and GABA(B2) receptor subunits in the cNS differs from that in peripheral tissues. (United States)

    Calver, A R; Medhurst, A D; Robbins, M J; Charles, K J; Evans, M L; Harrison, D C; Stammers, M; Hughes, S A; Hervieu, G; Couve, A; Moss, S J; Middlemiss, D N; Pangalos, M N


    GABA(B) receptors are G-protein-coupled receptors that mediate the slow and prolonged synaptic actions of GABA in the CNS via the modulation of ion channels. Unusually, GABA(B) receptors form functional heterodimers composed of GABA(B1) and GABA(B2) subunits. The GABA(B1) subunit is essential for ligand binding, whereas the GABA(B2) subunit is essential for functional expression of the receptor dimer at the cell surface. We have used real-time reverse transcriptase-polymerase chain reaction to analyse expression levels of these subunits, and their associated splice variants, in the CNS and peripheral tissues of human and rat. GABA(B1) subunit splice variants were expressed throughout the CNS and peripheral tissues, whereas surprisingly GABA(B2) subunit splice variants were neural specific. Using novel antisera specific to individual GABA(B) receptor subunits, we have confirmed these findings at the protein level. Analysis by immunoblotting demonstrated the presence of the GABA(B1) subunit, but not the GABA(B2) subunit, in uterus and spleen. Furthermore, we have shown the first immunocytochemical analysis of the GABA(B2) subunit in the brain and spinal cord using a GABA(B2)-specific antibody. We have, therefore, identified areas of non-overlap between GABA(B1) and GABA(B2) subunit expression in tissues known to contain functional GABA(B) receptors. Such areas are of interest as they may well contain novel GABA(B) receptor subunit isoforms, expression of which would enable the GABA(B1) subunit to reach the cell surface and form functional GABA(B) receptors.

  9. neu(c-erbB-2/HER2) and the epidermal growth factor receptor (EGFR) in breast cancer. (United States)

    Jardines, L; Weiss, M; Fowble, B; Greene, M


    One hundred and eighty thousand new cases of invasive breast cancer were diagnosed in 1992 within the United States. This disease affects approximately 1 out of 8 women in the US. Chemotherapy and/or hormonal therapy have shown some improved disease-free and/or overall survival rates. Unfortunately, this type of therapy is not directed specifically to the malignant cells, and systemic toxicities are observed. In order to develop site-specific treatment, the biology of the disease must be understood such that certain genes or their products which are involved in the pathogenesis of the disease can be targeted. Two structurally related tyrosine kinase growth factors, the epidermal growth factor receptor (EGFR) and c-erbB-2 (neu) have been identified in human breast cancer tissue and, in many instances, may function as oncogenes. The clinical data related to these two growth factor receptors as prognostic factors for the disease have been critically evaluated. Several problems with the critical studies were identified, and solutions were proposed to clarify the conflicting results reported in the studies which have attempted to examine whether c-erbB-2 (neu), in particular, is a prognostic indicator for breast cancer. In addition, data related to the structure of, ligands for and interaction between the proteins have been reviewed and presented with respect to their role in breast cancer development. A more thorough understanding of the genetic changes which contribute to the development of breast cancer will lead to more specific and less toxic treatment for this disease.

  10. Bradykinin : Inflammatory Product of the Coagulation System

    NARCIS (Netherlands)

    Hofman, Zonne; de Maat, Steven; Hack, C. Erik; Maas, Coen


    Episodic and recurrent local cutaneous or mucosal swelling are key features of angioedema. The vasoactive agents histamine and bradykinin are highly implicated as mediators of these swelling attacks. It is challenging to assess the contribution of bradykinin to the clinical expression of angioedema,

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

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


    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.

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


    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 (Pdifferential distribution of RXFP1 on endothelial and smooth muscle across the vasculature. In rats, mesenteric arteries exhibit the greatest functional response to chronic serelaxin treatment.

  13. Lys-[Leu8,des-Arg9]-bradykinin blocks lipopolysaccharide-induced SHR aorta hyperpolarization by inhibition of Ca(++)- and ATP-dependent K+ channels. (United States)

    Farias, Nelson C; Feres, Teresa; Paiva, Antonio C M; Paiva, Therezinha B


    The mediators involved in the hyperpolarizing effects of lipopolysaccharide and of the bradykinin B1 receptor agonist des-Arg9-bradykinin on the rat aorta were investigated by comparing the responses of aortic rings of spontaneously hypertensive and normotensive Wistar rats. Endothelized rings from hypertensive rats were hyperpolarized by des-Arg9-bradykinin and lipopolysaccharide, whereas de-endothelized rings responded to lipopolysaccharide but not to des-Arg9-bradykinin. In endothelized preparations, the responses to des-Arg9-bradykinin were inhibited by Nomega-nitro-L-arginine and iberiotoxin. De-endothelized ring responses to lipopolysaccharide were inhibited by iberiotoxin, glibenclamide and B1 antagonist Lys-[Leu8,des-Arg9]-bradykinin. This antagonist also inhibited hyperpolarization by des-Arg9-bradykinin and by the á2-adrenoceptor agonist, brimonidine. Our results indicate that Ca(2+)-sensitive K+ channels are the final mediators of the responses to des-Arg9-bradykinin, whereas both Ca(2+)- and ATP-sensitive K+ channels mediate the responses to lipopolysaccharide. The inhibitory effects of Lys-[Leu8,des-Arg9]-bradykinin is due to a direct action on Ca(2+)- and ATP-sensitive potassium channels.

  14. Cysteinyl leukotrienes mediate the response of submucosal ganglia from rat colon to bradykinin. (United States)

    Rehn, Matthias; Diener, Martin


    The aim of the present study was to find out the mechanism by which the inflammatory mediator, bradykinin, induces an increase of the cytosolic Ca(2+) concentration ([Ca(2+)](i)) in enteric neurons. For this purpose, ganglia in the isolated submucosa from rat colon were loaded with the Ca(2+)-sensitive dye, fura-2, and were exposed to bradykinin (2·10(-8)mol/l). Under control conditions, the kinin evoked a transient increase in [Ca(2+)](i). Preincubation with quinacrine or arachidonyltrifluoromethylketone (AACOCF(3)), i.e. blockers of cytosolic phospholipase A(2), prevented the raise of [Ca(2+)](i). This inhibition was mimicked by 5,8,11,14-eicosatetrayonic acid (ETYA), an inhibitor of cyclooxygenases as well as lipoxygenases, and by BWA4C, a selective inhibitor of lipoxygenases, whereas indomethacin was ineffective, suggesting the mediation of the kinin response by a lipoxygenase metabolite. Indeed, a leukotriene, leukotriene D(4) (LTD(4)), mimicked the effect of bradykinin. The LTD(4) receptor blocker, MK-571, inhibited the increase in [Ca(2+)](i) evoked by LTD(4) and by bradykinin. Consequently, bradykinin receptors in submucosal ganglia from rat colon are coupled to a stimulation of phospholipase A(2), the release of arachidonic acid and the production of LTD(4), which seems to be finally responsible for the change in the cytosolic Ca(2+) concentration.

  15. 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: [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)


    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

  16. Bradykinin Contributes to Sympathetic and Pressor Responses Evoked by Activation of Skeletal Muscle Afferents P2X in Heart Failure

    Directory of Open Access Journals (Sweden)

    Jihong Xing


    Full Text Available Background/Aims: Published data suggest that purinergic P2X receptors of muscle afferent nerves contribute to the enhanced sympathetic nervous activity (SNA and blood pressure (BP responses during static exercise in heart failure (HF. In this study, we examined engagement of bradykinin (BK in regulating responses of SNA and BP evoked by P2X stimulation in rats with HF. We further examined cellular mechanisms responsible for BK. We hypothesized that BK potentiates P2X currents of muscle dorsal root ganglion (DRG neurons, and this effect is greater in HF due to upregulation of BK kinin B2 and P2X3 receptor. As a result, BK amplifies muscle afferents P2X-mediated SNA and BP responses. Methods: Renal SNA and BP responses were recorded in control rats and rats with HF. Western Blot analysis and patch-clamp methods were employed to examine the receptor expression and function of DRG neurons involved in the effects of BK. Results: BK injected into the arterial blood supply of the hindlimb muscles heightened the reflex SNA and BP responses induced by P2X activation with α,β-methylene ATP to a greater degree in HF rats. In addition, HF upregulated the protein expression of kinin B2 and P2X3 in DRG and the prior application of BK increased the magnitude of α,β-methylene ATP-induced currents in muscle DRG neurons from HF rats. Conclusion: BK plays a facilitating role in modulating muscle afferent P2X-engaged reflex sympathetic and pressor responses. In HF, P2X responsivness is augmented due to increases in expression of kinin B2 and P2X3 receptors and P2X current activity.

  17. Molecular determinants of enterovirus 71 viral entry: cleft around GLN-172 on VP1 protein interacts with variable region on scavenge receptor B 2. (United States)

    Chen, Pan; Song, Zilin; Qi, Yonghe; Feng, Xiaofeng; Xu, Naiqing; Sun, Yinyan; Wu, Xing; Yao, Xin; Mao, Qunyin; Li, Xiuling; Dong, Wenjuan; Wan, Xiaobo; Huang, Niu; Shen, Xinliang; Liang, Zhenglun; Li, Wenhui


    Enterovirus 71 (EV71) is one of the major pathogens that cause hand, foot, and mouth disease outbreaks in young children in the Asia-Pacific region in recent years. Human scavenger receptor class B 2 (SCARB2) is the main cellular receptor for EV71 on target cells. The requirements of the EV71-SCARB2 interaction have not been fully characterized, and it has not been determined whether SCARB2 serves as an uncoating receptor for EV71. Here we compared the efficiency of the receptor from different species including human, horseshoe bat, mouse, and hamster and demonstrated that the residues between 144 and 151 are critical for SCARB2 binding to viral capsid protein VP1 of EV71 and seven residues from the human receptor could convert murine SCARB2, an otherwise inefficient receptor, to an efficient receptor for EV71 viral infection. We also identified that EV71 binds to SCARB2 via a canyon of VP1 around residue Gln-172. Soluble SCARB2 could convert the EV71 virions from 160 S to 135 S particles, indicating that SCARB2 is an uncoating receptor of the virus. The uncoating efficiency of SCARB2 significantly increased in an acidic environment (pH 5.6). These studies elucidated the viral capsid and receptor determinants of enterovirus 71 infection and revealed a possible target for antiviral interventions.

  18. 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.


    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

  19. 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


    , 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...... parameters of QT interval (corrected for heart rate), QRS interval, ST height, R amplitude, P amplitude, and PR interval. In addition, the left ventricular posterior wall thickness as determined by echocardiography correlated with ECG-determined ST height, R amplitude, QRS interval; echocardiographic left...... ventricular mass correlated with ECG-determined ST height and PR interval. In summary, we have determined phenotypic ECG criteria to differentiate ErbB2(tg) from WT genotypes in 98.8% of mice. This inexpensive and time-efficient ECG-based phenotypic method might be applied to differentiate between genotypes...

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

    Kusumawati, Widya; Keman, Kusnarman; Soeharto, Setyawati


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

  1. Bradykinin activates ADP-ribosyl cyclase in neuroblastoma cells: intracellular concentration decrease in NAD and increase in cyclic ADP-ribose. (United States)

    Higashida, Haruhiro; Salmina, Alla; Hashii, Minako; Yokoyama, Shigeru; Zhang, Jia-Sheng; Noda, Mami; Zhong, Zen-Guo; Jin, Duo


    ADP-ribosyl cyclase activity in the crude membrane fraction of neuroblastomaxglioma NGPM1-27 hybrid cells was measured by monitoring [(3)H] cyclic ADP-ribose (cADPR) formation from [(3)H] NAD(+). Bradykinin (BK) at 100nM increased ADP-ribosyl cyclase activity by about 2.5-fold. Application of 300nM BK to living NGPM1-27 cells decreased NAD(+) to 78% of the prestimulation level at 30s. In contrast, intracellular cADPR concentrations were increased by 2-3-fold during the period from 30 to 120s after the same treatment. Our results suggest that cADPR is one of the second messengers downstream of B(2) BK receptors.

  2. Expression of the Receptor Tyrosine Kinase EphB2 on Dendritic Cells Is Modulated by Toll-Like Receptor Ligation but Is Not Required for T Cell Activation.

    Directory of Open Access Journals (Sweden)

    Patrice N Mimche

    Full Text Available The Eph receptor tyrosine kinases interact with their ephrin ligands on adjacent cells to facilitate contact-dependent cell communication. Ephrin B ligands are expressed on T cells and have been suggested to act as co-stimulatory molecules during T cell activation. There are no detailed reports of the expression and modulation of EphB receptors on dendritic cells, the main antigen presenting cells that interact with T cells. Here we show that mouse splenic dendritic cells (DC and bone-marrow derived DCs (BMDC express EphB2, a member of the EphB family. EphB2 expression is modulated by ligation of TLR4 and TLR9 and also by interaction with ephrin B ligands. Co-localization of EphB2 with MHC-II is also consistent with a potential role in T cell activation. However, BMDCs derived from EphB2 deficient mice were able to present antigen in the context of MHC-II and produce T cell activating cytokines to the same extent as intact DCs. Collectively our data suggest that EphB2 may contribute to DC responses, but that EphB2 is not required for T cell activation. This result may have arisen because DCs express other members of the EphB receptor family, EphB3, EphB4 and EphB6, all of which can interact with ephrin B ligands, or because EphB2 may be playing a role in another aspect of DC biology such as migration.

  3. 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;


    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 homo...

  4. Co-expression of epidermal growth factor-receptor and c-erb B-2 proto-oncogene product in human salivary-gland adenocarcinoma cell line HSG and the implications for HSG cell autocrine growth. (United States)

    Kyakumoto, S; Kurokawa, R; Hoshino, M; Ota, M


    The autonomous proliferation of HSG cells is mediated by an autocrine growth factor, a 46K epidermal growth factor (EGF)-like molecule. The receptor for this molecule was investigated. Immunoprecipitation and immunoblotting revealed the expression of two possible receptor molecules, EGF-R and p185erbB-2, in HSG cells. Northern blotting also revealed the co-expression of 5.6-kb EGF-R mRNA and 4.6-kb c-erb B-2 mRNA. When the purified EGF-like molecule was added to the cultures, EGF-R but not p185erbB-2 was autophosphorylated. These results suggest that, although both EGF-R and p185erbB-2 are co-expressed in HSG cells, the EGF-R is the genuine receptor for the EGF-like molecule. However, there is a possibility that p185erB-2 is involved in the signal transduction system. This possibility was examined by using specific antibodies to human EGF-R (hEGF-R), p185erbB-2, and EGF to inhibit the functions of these molecules. Addition of these three antibodies to the cultures inhibited the growth of HSG cells. The antibodies to EGF-R and p185erbB-2 also caused morphological changes such as disturbances of the plasma membrane, and some cell death. Surprisingly, the effect of the anti-p185erbB-2 antibody on growth inhibition and morphology was stronger than that of the anti-hEGF-R antibody. Thus, p185erB-2 expressed in HSG cells has an important function in the signal transduction of HSG cell growth.

  5. Characterization of kinin receptors by bioassays. (United States)

    Gobeil, F; Regoli, D


    1. Using the classical pharmacological criteria recommended by Schild, namely the order of potency of selective agonists (e.g., bradykinin, desArg9-bradykinin, [Hyp3]BK and [Aib7]BK) and the apparent affinity of competitive antagonists (e.g., DArg[Hyp3,DPhe7,Leu8]BK and WIN 64338), we have attempted to characterize B2 receptor subtypes. It has been shown that vascular tissues (e.g., dog carotid and renal arteries, rabbit jugular vein and rabbit aorta) are very sensitive to kinin agonists and antagonists (pD2 and pA2 values for BK and HOE 140 on B2 receptors are 8.5-10.1 and 9.2-9.4, respectively, and for desArg9BK and desArg9[Leu8]BK on B1 receptors they are 7.3-8.6 and 7.3-7.8, respectively). Mechanisms of action of kinins differ between pharmacological preparations. Kinin may act directly on the smooth muscle (e.g., rabbit jugular vein and rabbit aorta) as well as indirectly through other endogenous mediators such as nitric oxide (EDRF) (e.g., dog carotid and renal arteries) and prostaglandins (e.g., dog renal artery). 2. Pharmacological analysis of rabbit jugular vein (RJV) and guinea pig ileum (GPI) has revealed different sensitivities to certain synthetic analogs of BK and to competitive B2 receptor antagonists between the two tissues. 3. Agonist order of potency ([Hyp3]BK > BK > [Aib7]BK) obtained for RJV differed from that obtained for GPI (BK > or = [Aib7]BK > [Hyp3]BK). Competitive antagonists such as DArg[Hyp3, DPhe7, Leu8]BK and WIN 64338 discriminate in favor of B2A (RJV) and B2B (GPI) receptor subtypes, respectively. These data demonstrate the existence of B2 receptor subtypes. Correlation between data obtained in the present study and those reported for binding to the human B2 receptor support the view that the human receptor is similar to that of the rabbit.

  6. Angiotensin II type 2 receptor expression after vascular injury: differing effects of angiotensin-converting enzyme inhibition and angiotensin receptor blockade. (United States)

    Barker, Thomas A; Massett, Michael P; Korshunov, Vyacheslav A; Mohan, Amy M; Kennedy, Amy J; Berk, Bradford C


    It has been suggested that the effects of angiotensin II type 1 receptor (AT1R) blockers are in part because of angiotensin II type 2 receptor (AT2R) signaling. Interactions between the AT2R and kinins modulate cardiovascular function. Because AT2R expression increases after vascular injury, we hypothesized that the effects on vascular remodeling of the AT1R blocker valsartan and the ACE inhibitor benazepril require AT2R signaling through the bradykinin 1 and 2 receptors (B1R and B2R). To test this hypothesis, Brown Norway rats were assigned to 8 treatments (n=16): valsartan, valsartan+PD123319 (AT2R inhibitor), valsartan+des-arg9-[Leu8]-bradykinin (B1R inhibitor), valsartan+HOE140 (B2R inhibitor), benazepril, benazepril+HOE140, amlodipine, and vehicle. After 1 week of treatment, carotid balloon injury was performed. Two weeks later, carotids were harvested for morphometry and analysis of receptor expression by immunohistochemistry and Western blotting. Valsartan and benazepril significantly reduced the intima:media ratio compared with vehicle. Blockade of AT2R, B1R, or B2R in the presence of valsartan prevented the reduction seen with valsartan alone. B2R blockade inhibited the effect of benazepril. Injury increased AT1R, AT2R, B1R, and B2R expression. Treatment with valsartan but not benazepril significantly increased intima AT2R expression 2-fold compared with vehicle, which was not reversed by inhibition of AT2R, B1R, and B2R. Functionally, valsartan increased intimal cGMP levels compared with vehicle, and this increase was inhibited by blocking the AT2R, B1R, and B2R. Results suggest that AT2R expression and increased cGMP represent a molecular mechanism that differentiates AT1R blockers, such as valsartan, from angiotensin-converting enzyme inhibitors like benazepril.

  7. 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


    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...... and depended on continuous expression of DeltaNErbB2 but not on the activation of the ERK1/2 pathway. Interestingly, the expression of DeltaNErbB2 resulted also in the increased expression and phosphorylation of ErbB1 as well as in the prolonged ligand-induced activation of the ErbB1 signaling pathway...

  8. 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


    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 the membrane by confocal micros-copy ,and protein band was 44 kd which was identical to target band through Western blot .Conclusion The plas-mid pB2R-Venus was successfully constructed and transfected into HEK 293T cells .The recombinant plasmid can be used to BRET and FRET experiments ,which contribute to investigate the signal transduction mechanism and ex-plore pharmacal targets .%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

  9. Endothelin receptor B2 (EDNRB2 is responsible for the tyrosinase-independent recessive white (mo(w and mottled (mo plumage phenotypes in the chicken.

    Directory of Open Access Journals (Sweden)

    Keiji Kinoshita

    Full Text Available A mutation that confers white plumage with black eyes was identified in the Minohiki breed of Japanese native chicken (Gallus gallus domesticus. The white plumage, with a few partially pigmented feathers, was not associated with the tyrosinase gene, and displayed an autosomal recessive mode of inheritance against the pigmented phenotype. All F1 offspring derived from crosses with mottled chickens (mo/mo, which show characteristic pigmented feathers with white tips, had plumage with a mottled-like pattern. This result indicates that the white plumage mutation is a novel allele at the mo locus; we propose the gene symbol mo(w for this mutant allele. Furthermore, the F1 hybrid between the mo(w /mo(w chicken and the panda (s/s mutant of Japanese quail (Coturnix japonica, whose causative gene is the endothelin receptor B2 (EDNRB2 gene, showed a mo(w/mo(w chicken-like plumage, suggesting the possibility that the mutations in parental species are alleles of the same gene, EDNRB2. Nucleotide sequencing of the entire coding region of EDNRB2 revealed a non-synonymous G1008T substitution, which causes Cys244Phe amino acid substitution in exon 5 (which is part of the extracellular loop between the putative fourth and fifth transmembrane domains of EDNRB2 in the mutant chicken. This Cys244Phe mutation was also present in individuals of four Japanese breeds with white plumage. We also identified a non-synonymous substitution leading to Arg332His substitution that was responsible for the mottled (mo/mo plumage phenotype. These results suggest that the EDN3 (endothelin 3-EDNRB2 signaling is essential for normal pigmentation in birds, and that the mutations of EDNRB2 may cause defective binding of the protein with endothelins, which interferes with melanocyte differentiation, proliferation, and migration.

  10. 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


    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

  11. Expression of the EGF receptor family members ErbB2, ErbB3, and ErbB4 in germinal zones of the developing brain and in neurosphere cultures containing CNS stem cells. (United States)

    Kornblum, H I; Yanni, D S; Easterday, M C; Seroogy, K B


    The epidermal growth factor receptor family consists of four related tyrosine kinases: the epidermal growth factor receptor (EGF-R or ErbB), ErbB2, ErbB3, and ErbB4. These receptors are capable of extensive cross-activation upon the binding of their ligands - the EGF family of peptides for EGF-R and the neuregulins for ErbB3 and ErbB4. Since EGF-R is expressed by proliferating cells in the central nervous system (CNS), including multipotent CNS stem cells, we examined the expression of ErbB2, ErbB3 and ErbB4 in the germinal epithelia of the developing rat brain using in situ hybridization. ErbB2 and ErbB4 mRNAs were widely distributed within the germinal zones as early as E12. However, as development proceeded, ErbB2 mRNA was mainly present within the layers of cells immediately adjacent to the ventricular surface - the ventricular zone, while ErbB4 mRNA was predominantly expressed by subventricular zone cells, in the regions where these specialized germinal epithelia were present. ErbB3 mRNA distribution within germinal epithelia was more restricted, primarily confined to the diencephalon and rostral midbrain. Cultured neurospheres, which contain CNS stem cells, expressed ErbB2, ErbB4 and, to a lesser extent, ErbB3 protein as demonstrated by Western blot analysis. This expression declined during following differentiation. Heregulin-beta1, a neuregulin, had no effect on the proliferative capacity of neurospheres. Overall, our results indicate that ErbB2, ErbB3 and ErbB4 may play important and distinct roles in the genesis of the CNS. However, our in vitro data do not support a role for neuregulins in proliferation, per se, of CNS stem cells.

  12. 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, (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 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 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.

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

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


    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, (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 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 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.

  14. Cardiac-specific over-expression of epidermal growth factor receptor 2 (ErbB2 induces pro-survival pathways and hypertrophic cardiomyopathy in mice.

    Directory of Open Access Journals (Sweden)

    Polina Sysa-Shah

    Full Text Available BACKGROUND: Emerging evidence shows that ErbB2 signaling has a critical role in cardiomyocyte physiology, based mainly on findings that blocking ErbB2 for cancer therapy is toxic to cardiac cells. However, consequences of high levels of ErbB2 activity in the heart have not been previously explored. METHODOLOGY/PRINCIPAL FINDINGS: We investigated consequences of cardiac-restricted over-expression of ErbB2 in two novel lines of transgenic mice. Both lines develop striking concentric cardiac hypertrophy, without heart failure or decreased life span. ErbB2 transgenic mice display electrocardiographic characteristics similar to those found in patients with Hypertrophic Cardiomyopathy, with susceptibility to adrenergic-induced arrhythmias. The hypertrophic hearts, which are 2-3 times larger than those of control littermates, express increased atrial natriuretic peptide and β-myosin heavy chain mRNA, consistent with a hypertrophic phenotype. Cardiomyocytes in these hearts are significantly larger than wild type cardiomyocytes, with enlarged nuclei and distinctive myocardial disarray. Interestingly, the over-expression of ErbB2 induces a concurrent up-regulation of multiple proteins associated with this signaling pathway, including EGFR, ErbB3, ErbB4, PI3K subunits p110 and p85, bcl-2 and multiple protective heat shock proteins. Additionally, ErbB2 up-regulation leads to an anti-apoptotic shift in the ratio of bcl-xS/xL in the heart. Finally, ErbB2 over-expression results in increased activation of the translation machinery involving S6, 4E-BP1 and eIF4E. The dependence of this hypertrophic phenotype on ErbB family signaling is confirmed by reduction in heart mass and cardiomyocyte size, and inactivation of pro-hypertrophic signaling in transgenic animals treated with the ErbB1/2 inhibitor, lapatinib. CONCLUSIONS/SIGNIFICANCE: These studies are the first to demonstrate that increased ErbB2 over-expression in the heart can activate protective signaling

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

    Directory of Open Access Journals (Sweden)

    A Noor


    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.

  16. Bradykinin-induced relaxation of coronary microarteries: S-nitrosothiols as EDHF?

    NARCIS (Netherlands)

    W.W. Batenburg (Wendy); R. Popp (Rudiger); I. Fleming (Ingrid); R. de Vries (René); I.M. Garrelds (Ingrid); P.R. Saxena (Pramod Ranjan); A.H.J. Danser (Jan)


    textabstract1. To investigate whether S-nitrosothiols, in addition to NO, mediate bradykinin-induced vasorelaxation, porcine coronary microarteries (PCMAs) were mounted in myographs. 2. Following preconstriction, concentration-response curves (CRCs) were constructed to bradykinin,

  17. B2B marketing


    Pospíšilová, Lucie


    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...

  18. Effects of chlorobutanol and bradykinin on myocardial excitation. (United States)

    Hermsmeyer, K; Aprigliano, O


    The negative inotropic effect of a commonly used formulation of bradykinin (Sandoz BRS-640) was found to be due to chlorobutanol, a constituent of the preparation. Solutions containing up to 100 mug of crystalline bradykinin/ml had no effect on tension or action-potential shape. Chlorobutanol (500 mug/ml) caused a 30% decrease in contraction amplitude and a 20% increase in action-potential duration. Chlorobutanol lowered conduction velocity and induced conduction failure and automaticity within isolated ventricular muscle strips. Chlorobutanol affected neither positive nor negative treppe. We conclude that bradykinin has no direct action on toad, frog, or rat myocardium. However, chlorobutanol does have direct effects on myocardial cells, acting on the cell membrane and decreasing isometric tension produced by the heart.

  19. Expression of biomarkers (p53, transforming growth factor alpha, epidermal growth factor receptor, c-erbB-2/neu and the proliferative cell nuclear antigen) in oropharyngeal squamous cell carcinomas



    Using immunohistochemistry, expression of p53, transforming growth factor-alpha (TGF-α), epidermal growth factor receptor (EGFR), c-erbB-2/neu and proliferating cell nuclear antigen (PCNA) was examined in 26 fresh frozen tissue specimens of oropharyngeal squamous cell carcinomas (SCCs). p53 gene mutations were examined by polymerase chain reaction (PCR)/DNA sequencing methods in 22 carcinomas. The findings were examined for correlations with patients’ clinicopathological parameters. Expressio...

  20. 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


    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.

  1. Anti-Ephrin Type-B Receptor 2 (EphB2) and Anti-Three Prime Histone mRNA EXonuclease 1 (THEX1) Autoantibodies in Scleroderma and Lupus (United States)

    Azzouz, Doua F.; Martin, Gabriel V.; Arnoux, Fanny; Balandraud, Nathalie; Martin, Thierry; Dubucquoi, Sylvain; Hachulla, Eric; Farge-Bancel, Dominique; Tiev, Kiet; Cabane, Jean; Bardin, Nathalie; Chiche, Laurent; Martin, Marielle; Caillet, Eléonore C.; Kanaan, Sami B.; Harlé, Jean Robert; Granel, Brigitte; Diot, Elisabeth; Roudier, Jean; Auger, Isabelle; Lambert, Nathalie C.


    In a pilot ProtoArray analysis, we identified 6 proteins out of 9483 recognized by autoantibodies (AAb) from patients with systemic sclerosis (SSc). We further investigated the 6 candidates by ELISA on hundreds of controls and patients, including patients with Systemic Lupus Erythematosus (SLE), known for high sera reactivity and overlapping AAb with SSc. Only 2 of the 6 candidates, Ephrin type-B receptor 2 (EphB2) and Three prime Histone mRNA EXonuclease 1 (THEX1), remained significantly recognized by sera samples from SSc compared to controls (healthy or with rheumatic diseases) with, respectively, 34% versus 14% (P = 2.10−4) and 60% versus 28% (P = 3.10−8). Above all, EphB2 and THEX1 revealed to be mainly recognized by SLE sera samples with respectively 56%, (P = 2.10−10) and 82% (P = 5.10−13). As anti-EphB2 and anti-THEX1 AAb were found in both diseases, an epitope mapping was realized on each protein to refine SSc and SLE diagnosis. A 15-mer peptide from EphB2 allowed to identify 35% of SLE sera samples (N = 48) versus only 5% of any other sera samples (N = 157), including SSc sera samples. AAb titers were significantly higher in SLE sera (P<0.0001) and correlated with disease activity (p<0.02). We could not find an epitope on EphB2 protein for SSc neither on THEX1 for SSc or SLE. We showed that patients with SSc or SLE have AAb against EphB2, a protein involved in angiogenesis, and THEX1, a 3’-5’ exoribonuclease involved in histone mRNA degradation. We have further identified a peptide from EphB2 as a specific and sensitive tool for SLE diagnosis. PMID:27617966

  2. Localisation Microscopy of Breast Epithelial ErbB-2 Receptors and Gap Junctions: Trafficking after γ-Irradiation, Neuregulin-1β, and Trastuzumab Application (United States)

    Pilarczyk, Götz; Nesnidal, Ines; Gunkel, Manuel; Bach, Margund; Bestvater, Felix; Hausmann, Michael


    In cancer, vulnerable breast epithelium malignance tendency correlates with number and activation of ErbB receptor tyrosine kinases. In the presented work, we observe ErbB receptors activated by irradiation-induced DNA injury or neuregulin-1β application, or alternatively, attenuated by a therapeutic antibody using high resolution fluorescence localization microscopy. The gap junction turnover coinciding with ErbB receptor activation and co-transport is simultaneously recorded. DNA injury caused by 4 Gray of 6 MeV photon γ-irradiation or alternatively neuregulin-1β application mobilized ErbB receptors in a nucleograde fashion—a process attenuated by trastuzumab antibody application. This was accompanied by increased receptor density, indicating packing into transport units. Factors mobilizing ErbB receptors also mobilized plasma membrane resident gap junction channels. The time course of ErbB receptor activation and gap junction mobilization recapitulates the time course of non-homologous end-joining DNA repair. We explain our findings under terms of DNA injury-induced membrane receptor tyrosine kinase activation and retrograde trafficking. In addition, we interpret the phenomenon of retrograde co-trafficking of gap junction connexons stimulated by ErbB receptor activation. PMID:28208769

  3. The differential expression of EphB2 and EphB4 receptor kinases in normal bladder and in transitional cell carcinoma of the bladder.

    Directory of Open Access Journals (Sweden)

    Xiuqing Li

    Full Text Available Effective treatment of transitional cell carcinoma (TCC of the bladder requires early diagnosis. Identifying novel molecular markers in TCC would guide the development of diagnostic and therapeutic targets. Ephrins mediate signals via tyrosine kinase activity that modulates diverse physiologic and developmental processes, and ephrins are increasingly implicated in carcinogenesis. The aim of our study was to examine the differential regulation of EphB4 and EphB2 in normal bladder and in TCC of the bladder in 40 patients undergoing radical cystectomy for curative intent. Immunostaining and Western blotting revealed that normal urothelium expresses EphB2 (20 of 24 cases, 83% of the time not EphB4 (0 of 24 cases, 0%. In sharp contrast, TCC specimens show loss of EphB2 expression (0 of 34 cases, 0% and gain of EphB4 expression (32 of 34, 94%. Furthermore, EphB4 signal strength statistically correlated with higher tumor stage, and trended toward the presence of carcinoma in situ (CIS. These results are confirmed by analysis of normal urothelial and tumor cell lines. EphB2 is not a survival factor in normal urothelium, while EphB4 is a survival factor in TCC. Treatment of bladder tumor xenograft with an EphB4 inhibitor sEphB4-HSA leads to 62% tumor regression and complete remission when combined with Bevacizumab. Furthermore, tissue analysis revealed that sEphB4-HSA led to increased apoptosis, decreased proliferation, and reduced vessel density, implicating direct tumor cell targeting as well as anti-angiogenesis effect. In summary loss of EphB2 and gain of EphB4 expression represents an inflection point in the development, growth and possibly progression of TCC. Therapeutic compounds targeting EphB4 have potential for diagnosing and treating TCC.

  4. Efecto de la dieta y de los genes PPARγ2 y b2-adrenérgico en el metabolismo energético y en la composición corporal de mujeres obesas Effect of diet and PPARγ2 and b2-adrenergic receptor genes on energy metabolism and body composition in obese women

    Directory of Open Access Journals (Sweden)

    E. L. Rosado


    Glu la ingesta de AGPI puede resultar en mayor pérdida de peso corporal.Objective: To evaluate the effect of diet and PPARγ2 and b2-adrenergic receptor genes on energy metabolism and body composition in obese women. Material and methods: 60 obese women, aged 34.59 ± 7.56 years were studied at the Department of Physiology and Nutrition at Navarra University. Anthropometric, biochemical,metabolic and molecular evaluations were carried out, and the women were submitted to short-term and longterm hypocaloric diets, varying the macronutrients. The groups were formed according to gene polymorphism, as follows: Pro12Pro(PPARγ2/Gln27Gln (ί2-adrenergic receptor genes - A, Pro12Pro (PPARγ2/Gln27Glu (b2- adrenergic receptor genes - B, Pro12Pro (PPARγ2/Glu27Glu (b2-adrenergic receptor genes-C and Pro1Ala (PPARγ2/Gln27Glu (b2-adrenergic receptor genes - D. Results: In group A, fat oxidation was correlated positively with body mass index (BMI, but an increase in fat and saturated fatty acids (SFA in the diet did not reflect in increased oxidation. In group B, total fat and SFA intake did not lead to fat oxidation increase. In group C, fat and complex carbohydrates (CHO resulted in lower fat oxidation, and long-term increase of monounsaturated fatty acid (MUFA intake resulted in increase of CHO oxidation and smaller weight loss. In group D, greater energy expenditure was obtained after diet high in SFA in a short-term, and fat basal and postprandial oxidation correlated positively with its intake. Hypocaloric diet high in polyunsaturated fatty acid (PUFA resulted inincrease of fat oxidation. Conclusions: Polymorphism in PPARγ2 gene resulted in increased fat oxidation, regardless of genotype of ί2- adrenergic receptor gene. It is recommended control of the total intake of fats and SFA in Pro12Pro/Gln27Gln and Pro12Pro/Gln27Glu, and complex CHO and MUFA in Pro12Pro/Glu27Glu. In Pro12Ala/Gln27Glu, AGPI intake can result in greater body weight loss.

  5. 雌激素受体、孕激素受体及原癌基因CerbB-2表达水平与乳腺浸润性导管癌超声乳腺影像报告和数据系统分级的关系%Relationship between the estrogen receptor, progesterone receptor and CerbB-2 expression levels and breast imaging re-porting and data system in invasive breast cancer patients

    Institute of Scientific and Technical Information of China (English)

    厉亚林; 李波


    目的:探讨雌激素受体(estrogen receptor, ER)、孕激素受体(progesterone receptor, PR)、原癌基因(CerbB-2)表达水平与乳腺浸润性导管癌( invasive breast cancers , IDC)超声乳腺影像报告和数据系统分级( breast imaging reporting and data system, BI-RADS)的关系。方法对2010年9月~2014年9月医院收治的120例IDC患者行超声检查并进行BI-RADS分级,采用免疫组化法检测患者ER、PR、CerbB-2阳性表达情况,分析BI-RADS分级与ER、PR、CerbB-2阳性表达的关系。结果肿块边缘有毛刺征者ER、PR表达阳性率显著高于边缘无毛刺征者( P <0.05);肿块内部钙化者CerbB-2表达阳性率显著高于无钙化者( P <0.05);肿块内血流0~Ⅰ级者ER、PR、CerbB-2表达阳性率显著高于Ⅱ~Ⅲ级者( P <0.05);肿块大小、后方回声有无衰减、UE评分与ER、PR、CerbB-2表达阳性率无明显相关性( P >0.05)。 ER、PR、CerbB-2表达阳性的IDC患者BI-RADS分级均显著高于表达阴性者( P <0.05)。结论 IDC患者超声征象能够在一定程度上预测ER、PR、CerbB-2表达的水平,从而为IDC的治疗、预后评估提供参考。%Objective To explore the relationship between the estrogen receptor , progesterone receptor and CerbB-2 expres-sion levels and breast imaging reporting and data system in invasive breast cancer patients .Methods 120 patients with invasive breast cancers selected from september 2014 to september 2010 underwent ultrasonic examination and BI-RADS classification. CerbB-2, PR and ER positive expression were detected by immunohistochemistry method .We analyzed relationship of BI-RADS grading and ER ,PR and CerbB-2 positive expression .Results Tumor margin spiculation in ER and PR positive expression rate was significantly higher than the edge without spiculation persons ( P 0.05).The positive expression of ER, PR, CerbB-2 in IDC patients with BI

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

    DEFF Research Database (Denmark)

    Jing, Fei; Mogi, Masaki; Sakata, Akiko


    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...... 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...... 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....

  7. The Differential Expression of EphB2 and EphB4 Receptor Kinases in Normal Bladder and in Transitional Cell Carcinoma of the Bladder


    Xiuqing Li; Choi, Wesley W.; Rui Yan; Haiyang Yu; Valery Krasnoperov; S Ram Kumar; Anne Schuckman; Klumpp, David J.; Chong-Xian Pan; David Quinn; Gill,Inderbir S.; Gill, Parkash S.; Ren Liu


    Effective treatment of transitional cell carcinoma (TCC) of the bladder requires early diagnosis. Identifying novel molecular markers in TCC would guide the development of diagnostic and therapeutic targets. Ephrins mediate signals via tyrosine kinase activity that modulates diverse physiologic and developmental processes, and ephrins are increasingly implicated in carcinogenesis. The aim of our study was to examine the differential regulation of EphB4 and EphB2 in normal bladder and in TCC o...

  8. Aberrant gonadotropin-releasing hormone receptor (GnRHR) expression and its regulation of CYP11B2 expression and aldosterone production in adrenal aldosterone-producing adenoma (APA). (United States)

    Nakamura, Yasuhiro; Hattangady, Namita G; Ye, Ping; Satoh, Fumitoshi; Morimoto, Ryo; Ito-Saito, Takako; Sugawara, Akira; Ohba, Koji; Takahashi, Kazuhiro; Rainey, William E; Sasano, Hironobu


    Aberrant expression of gonadotropin-releasing hormone receptor (GnRHR) has been reported in human adrenal tissues including aldosterone-producing adenoma (APA). However, the details of its expression and functional role in adrenals are still not clear. In this study, quantitative RT-PCR analysis revealed the mean level of GnRHR mRNA was significantly higher in APAs than in human normal adrenal (NA) (P=0.004). GnRHR protein expression was detected in human NA and neoplastic adrenal tissues. In H295R cells transfected with GnRHR, treatment with GnRH resulted in a concentration-dependent increase in CYP11B2 reporter activity. Chronic activation of GnRHR with GnRH (100nM), in a cell line with doxycycline-inducible GnRHR (H295R-TR/GnRHR), increased CYP11B2 expression and aldosterone production. These agonistic effects were inhibited by blockers for the calcium signaling pathway, KN93 and calmidazolium. These results suggest GnRH, through heterotopic expression of its receptor, may be a potential regulator of CYP11B2 expression levels in some cases of APA.

  9. Active G protein-coupled receptors (GPCR), matrix metalloproteinases 2/9 (MMP2/9), heparin-binding epidermal growth factor (hbEGF), epidermal growth factor receptor (EGFR), erbB2, and insulin-like growth factor 1 receptor (IGF-1R) are necessary for trenbolone acetate-induced alterations in protein turnover rate of fused bovine satellite cell cultures. (United States)

    Thornton, K J; Kamanga-Sollo, E; White, M E; Dayton, W R


    Trenbolone acetate (TBA), a testosterone analog, increases protein synthesis and decreases protein degradation in fused bovine satellite cell (BSC) cultures. However, the mechanism through which TBA alters these processes remains unknown. Recent studies indicate that androgens improve rate and extent of muscle growth through a nongenomic mechanism involving G protein-coupled receptors (GPCR), matrix metalloproteinases (MMP), heparin-binding epidermal growth factor (hbEGF), the epidermal growth factor receptor (EGFR), erbB2, and the insulin-like growth factor-1 receptor (IGF-1R). We hypothesized that TBA activates GPCR, resulting in activation of MMP2/9 that releases hbEGF, which activates the EGFR and/or erbB2. To determine whether the proposed nongenomic pathway is involved in TBA-mediated alterations in protein turnover, fused BSC cultures were treated with TBA in the presence or absence of inhibitors for GPCR, MMP2/9, hbEGF, EGFR, erbB2, or IGF-1R, and resultant protein synthesis and degradation rates were analyzed. Assays were replicated at least 9 times for each inhibitor experiment utilizing BSC cultures obtained from at least 3 different steers that had no previous exposure to steroid compounds. As expected, fused BSC cultures treated with 10 n TBA exhibited increased ( BSC cultures with 10 n TBA in the presence of inhibitors for GPCR, MMP2/9, hbEGF, EGFR, erbB2, or IGF-1R suppressed ( 0.05) effect on TBA-mediated decreases in protein degradation. However, inhibition of both EGFR and erbB2 in the presence of 10 n TBA resulted in decreased ( BSC cultures treated with 10 n TBA exhibit increased ( BSC cultures.

  10. Strain-dependent effects of diazepam and the 5-HT2B/2C receptor antagonist SB 206553 in spontaneously hypertensive and Lewis rats tested in the elevated plus-maze

    Directory of Open Access Journals (Sweden)

    Takahashi R.N.


    Full Text Available The 5-HT2B/2C receptor antagonist SB 206553 exerts anxiolytic effects in rat models of anxiety. However, these effects have been reported for standard rat strains, thus raising the issue of SB 206553 effects in rat strains displaying different levels of anxiety. Herein, the effects of SB 206553 in a 5-min elevated plus-maze test of anxiety were compared to those of the reference anxiolytic, diazepam, in two rat strains respectively displaying high (Lewis rats and low (spontaneously hypertensive rats, SHR anxiety. Diazepam (0.37, 0.75, or 1.5 mg/kg; 30 min before testing increased in a dose-dependent manner the behavioral measures in SHR, but not in Lewis rats. On the other hand, SB 206553 (1.25, 2.5, or 5 mg/kg; 30 min before testing failed to alter the anxiety parameters in both strains, whereas it increased closed arm entries in Lewis rats, suggesting that it elicited hyperactivity in the latter strain. Accordingly, the hypolocomotor effect of the nonselective 5-HT2B/2C receptor agonist m-chlorophenylpiperazine (1.5 mg/kg ip 20 min before a 15-min exposure to an activity cage was prevented by the 1.25 and 2.5 mg/kg doses of SB 206553 in Lewis rats and SHR, respectively. Compared with SHR, Lewis rats may display a lower response to benzodiazepine-mediated effects and a more efficient control of locomotor activity by 5-HT2B/2C receptors.

  11. Cooperación oncogénica entre la citoquina pro-inflamatoria SP y el receptor tirosina quinasa ErbB-2/HER2


    Garcia Recio, Susana


    INTRODUCCIÓN: La inflamación es un sello distintivo del cáncer. La inflamación crónica está fuertemente relacionada con el desarrollo y la progresión tumoral y suministra al tumor múltiples citoquinas proinflamatorias que pueden modular la señalización de la célula tumoral. Este es el caso de la Sustancia P (SP), una citoquina pro-inflamatoria/neuropéptido presente en el microambiente tumoral perteneciente a la familia de las taquiquininas y que señaliza principalmente a través de su receptor...

  12. Presenilin mediates neuroprotective functions of ephrinB and brain-derived neurotrophic factor and regulates ligand-induced internalization and metabolism of EphB2 and TrkB receptors. (United States)

    Barthet, Gael; Dunys, Julie; Shao, Zhiping; Xuan, Zhao; Ren, Yimin; Xu, Jindong; Arbez, Nicolas; Mauger, Gweltas; Bruban, Julien; Georgakopoulos, Anastasios; Shioi, Junichi; Robakis, Nikolaos K


    Activation of EphB receptors by ephrinB (efnB) ligands on neuronal cell surface regulates important functions, including neurite outgrowth, axonal guidance, and synaptic plasticity. Here, we show that efnB rescues primary cortical neuronal cultures from necrotic cell death induced by glutamate excitotoxicity and that this function depends on EphB receptors. Importantly, the neuroprotective function of the efnB/EphB system depends on presenilin 1 (PS1), a protein that plays crucial roles in Alzheimer's disease (AD) neurodegeneration. Furthermore, absence of one PS1 allele results in significantly decreased neuroprotection, indicating that both PS1 alleles are necessary for full expression of the neuroprotective activity of the efnB/EphB system. We also show that the ability of brain-derived neurotrophic factor (BDNF) to protect neuronal cultures from glutamate-induced cell death depends on PS1. Neuroprotective functions of both efnB and BDNF, however, were independent of γ-secretase activity. Absence of PS1 decreases cell surface expression of neuronal TrkB and EphB2 without affecting total cellular levels of the receptors. Furthermore, PS1-knockout neurons show defective ligand-dependent internalization and decreased ligand-induced degradation of TrkB and Eph receptors. Our data show that PS1 mediates the neuroprotective activities of efnB and BDNF against excitotoxicity and regulates surface expression and ligand-induced metabolism of their cognate receptors. Together, our observations indicate that PS1 promotes neuronal survival by regulating neuroprotective functions of ligand-receptor systems.

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

    Directory of Open Access Journals (Sweden)

    Paulo Roberto Wille


    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.

  14. An Unexpected Mode Of Binding Defines BMS948 as A Full Retinoic Acid Receptor β (RARβ, NR1B2 Selective Agonist.

    Directory of Open Access Journals (Sweden)

    Eswarkumar Nadendla

    Full Text Available Retinoic acid is an important regulator of cell differentiation which plays major roles in embryonic development and tissue remodeling. The biological action of retinoic acid is mediated by three nuclear receptors denoted RARα, β and γ. Multiple studies support that RARβ possesses functional characteristics of a tumor suppressor and indeed, its expression is frequently lost in neoplastic tissues. However, it has been recently reported that RARβ could also play a role in mammary gland tumorigenesis, thus demonstrating the important but yet incompletely understood function of this receptor in cancer development. As a consequence, there is a great need for RARβ-selective agonists and antagonists as tools to facilitate the pharmacological analysis of this protein in vitro and in vivo as well as for potential therapeutic interventions. Here we provide experimental evidences that the novel synthetic retinoid BMS948 is an RARβ-selective ligand exhibiting a full transcriptional agonistic activity and activating RARβ as efficiently as the reference agonist TTNPB. In addition, we solved the crystal structures of the RARβ ligand-binding domain in complex with BMS948 and two related compounds, BMS641 and BMS411. These structures provided a rationale to explain how a single retinoid can be at the same time an RARα antagonist and an RARβ full agonist, and revealed the structural basis of partial agonism. Finally, in addition to revealing that a flip by 180° of the amide linker, that usually confers RARα selectivity, accounts for the RARβ selectivity of BMS948, the structural analysis uncovers guidelines for the rational design of RARβ-selective antagonists.

  15. 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))


    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.

  16. Crystallization and preliminary X-ray analysis of the low-affinity complex between human leukocyte antigen-G (HLA-G) and leukocyte Ig-like receptor B2 (LILRB2). (United States)

    Shiroishi, Mitsunori; Maenaka, Katsumi


    Human leukocyte antigen-G (HLA-G) is a nonclassical MHC class I (MHCI) molecule that is expressed mainly on placenta trophoblast cells. Leukocyte Ig-like receptor B2 (LILRB2) is a human inhibitory immune receptor that recognizes HLA-G with a higher affinity than any other MHCI although this interaction is only in the microM range. The interaction between HLA-G and LILRB2 seems to play a dominant role in the escape of the fetus from the maternal immune response. Here we report the crystallization and x-ray analysis of the LILRB2/HLA-G complex. The extracellular domains of HLA-G and LILRB2 were expressed in Escherichia coli, refolded and purified. The initial crystallization trials using novel PEG-based screening sets provided crystals of the LILRB2/HLA-G complex with 40-50% PEG400 as the precipitant. These crystals belong to space group P3(1)21 (a=b=81.4 A, c=186.7 A, gamma=120 degrees ). Dehydration of the crystals by soaking them in a solution containing a higher concentration of PEG400 dramatically improved the resolution and also the mosaicity.

  17. 乳腺癌雌激素受体、孕激素受体和C-erbB-2在不同新辅助化疗前后的变化%Changes of estrogen receptor, progesterone receptor and C-erbB-2 expressions in different scheme pre-and post-neoadjuvant chemotherapies for breast cancer

    Institute of Scientific and Technical Information of China (English)

    史蓬亮; 张乃千; 张国强


    新辅助化疗在局部晚期乳腺癌的治疗中已被越来越广泛的应用.近年来研究表明,不同新辅助化疗前后肿瘤组织中雌激素受体(ER)、孕激素受体(PR)和人类表皮生长因子受体-2(C-erbB-2)的表达可能发生变化.在同时含有蒽环类及紫衫类化疗药物的新辅助化疗方案中改变较为明显,而在以蒽环类化疗药物为主的方案中无明显变化.%Neoadjuvant chemotherapy is widely used in the therapy of locally advanced breast cancer.In the recent studies,the expressions of ER,PR and C-erbB-2 in tumor may change in different scheme preand post-neoadjuvant chemotherapies for breast cancer.It is obviously changed in the neoadjuvant chemotherapy scheme of anthracyclines and paclitaxel/docetaxel,but hardly changed in anthracycline-based neoadjuvant chemotherapy scheme.

  18. 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


    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

  19. Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. (United States)

    Bandell, Michael; Story, Gina M; Hwang, Sun Wook; Viswanath, Veena; Eid, Samer R; Petrus, Matt J; Earley, Taryn J; Patapoutian, Ardem


    Six members of the mammalian transient receptor potential (TRP) ion channels respond to varied temperature thresholds. The natural compounds capsaicin and menthol activate noxious heat-sensitive TRPV1 and cold-sensitive TRPM8, respectively. The burning and cooling perception of capsaicin and menthol demonstrate that these ion channels mediate thermosensation. We show that, in addition to noxious cold, pungent natural compounds present in cinnamon oil, wintergreen oil, clove oil, mustard oil, and ginger all activate TRPA1 (ANKTM1). Bradykinin, an inflammatory peptide acting through its G protein-coupled receptor, also activates TRPA1. We further show that phospholipase C is an important signaling component for TRPA1 activation. Cinnamaldehyde, the most specific TRPA1 activator, excites a subset of sensory neurons highly enriched in cold-sensitive neurons and elicits nociceptive behavior in mice. Collectively, these data demonstrate that TRPA1 activation elicits a painful sensation and provide a potential molecular model for why noxious cold can paradoxically be perceived as burning pain.

  20. The structure, stability, and infrared spectrum of B 2N, B 2N +, B 2N -, BO, B 2O and B 2N 2. (United States)

    Martin, J. M. L.; François, J. P.; Gijbels, R.


    The structure, infrared spectrum, and heat of formation of B 2N, B 2N -, BO, and B 2O have been studied ab initio. B 2N is very stable; B 2O even more so. B 2N, B 2N -, B 2O, and probably B 2N + have symmetric linear ground-state structures; for B 2O, an asymmetric linear structure lies about 12 kcal/mol above the ground state. B 2N +, B 2N - and B 2O have intense asymmetric stretching frequencies, predicted near 870, 1590 and 1400 cm -1, respectively. Our predicted harmonic frequencies and isotopic shifts for B 2O confirm the recent experimental identification by Andrews and Burkholder. Absorptions at 1889.5 and 1998.5 cm -1 in noble-gas trapped boron nitride vapor belong the BNB and BNBN ( 3Π), respectively; a tentative assignment of 882.5 cm -1 to BNB + is proposed. Total atomization energies Σ De (Σ D0) are computed (accuracy ±2 kcal/mol) as: BO 193.1 (190.4), B 2O 292.5 (288.7), B 2N 225.0 (250.3) kcal/mol. The ionization potential and electron affinity of B 2N are predicted to be 8.62±0.1 and 3.34±0.1 eV. The MP4-level additivity approximations involved in G1 theory results in errors on the order of 1 kcal/mol in the Σ De values.

  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;


    -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....... In addition, PPTs were significantly decreased (Peffect of bradykinin in producing experimental muscle pain and muscle hyperalgesia to mechanical stimuli. The combination of serotonin and bradykinin can produce muscle...

  2. EGF受体介导c-erbB2癌基因反义寡核苷酸对p185蛋白表达的影响%The effect of c-erbB2 oncogene antisense oligodeoxynucleotide for p185 protein expression by EGF receptor

    Institute of Scientific and Technical Information of China (English)

    刘方欣; 谢娟; 李少林; 张玉诺



  3. 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


    increased both in muscle (from 0.48 +/- 0.07 micromol l(-1) to 1.59 +/- 0.35 micromol l(-1); P muscular activity increases the interstitial concentrations...... of bradykinin and adenosine in both skeletal muscle and the connective tissue around its adjacent tendon. These findings support a role for bradykinin and adenosine in exercise-induced hyperaemia in skeletal muscle and suggest that bradykinin and adenosine are potential regulators of blood flow in peritendinous...

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

    Directory of Open Access Journals (Sweden)

    Čokić Vladan P.


    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

  5. Ephrin B2受体对皮质脑梗死远隔部位血管发生和神经可塑性的影响%The Effects of Ephrin Receptor B2 on Angiogenesis and Neuroplasticity in Areas Remote From the Cortical Infarction

    Institute of Scientific and Technical Information of China (English)

    侯清华; 曾进胜


    脑梗死不仅是局部损伤,而且还会引起远隔缺血部位的继发性损伤,这种继发性损伤会阻碍神经功能的恢复.Ephrin B2受体(EphB2)在中枢神经系统发育和修复机制中起着重要作用.利用特异性抑制剂阻断脑内EphB2的作用,能促进实验性脑梗死后内源性神经干细胞增殖和迁移,改善神经功能,并可能影响远隔部位血管发生和神经可塑性,有望成为减轻脑梗死远隔部位损伤和促进神经功能恢复的新途径.

  6. Bradykinin-induced bronchoconstriction: inhibition by nedocromil sodium and sodium cromoglycate. (United States)

    Dixon, C M; Barnes, P J


    1. The effects of inhaled nedocromil sodium and sodium cromoglycate on bradykinin-induced bronchoconstriction have been studied in a double-blind, placebo controlled study, in eight mild asthmatic subjects. 2. The subjects attended on four occasions. Fifteen minutes after drug pre-treatment a bradykinin challenge was performed. Increasing concentrations were inhaled until a greater than 40% fall in expiratory flow at 30% of vital capacity from a partial flow volume manoeuvre (V p30) was demonstrated. 3. Inhaled bradykinin (0.06-8.0 mg ml-1) caused dose-related bronchoconstriction with the geometric mean cumulative dose causing a 40% fall in V p30 (PD40) of 0.035 (95% CI: 0.02-0.07) mumol, after placebo inhalation, which was similar to that measured before the trial (0.04: 0.02-0.09 mumol). 4. Both nedocromil sodium (4 mg) and sodium cromoglycate (10 mg) gave significant protection (P less than 0.05) against bradykinin-induced bronchoconstriction (PD40 0.37: 0.19-0.72 mumol after nedocromil sodium and 0.22: 0.11-0.49 after sodium cromoglycate). 5. Since bradykinin-induced bronchoconstriction is probably neurally mediated we conclude that both nedocromil sodium and sodium cromoglycate have an action on neural pathways which may be useful in the control of asthma symptoms. PMID:2547408

  7. Bradykinin augments EGF-induced airway smooth muscle proliferation by activation of conventional protein kinase C isoenzymes

    NARCIS (Netherlands)

    Gosens, R; Bromhaar, MMG; Maarsingh, H; ten Damme, A; Meurs, H; Zaagsma, J; Nelemans, SA


    This study aims to investigate the effects of bradykinin, alone and in combination with growth factors on proliferation of cultured bovine tracheal smooth muscle cells. Bradykinin did not induce mitogenic responses by itself, but concentration-dependently augmented growth factor-induced [H-3]thymidi

  8. Specific immunotherapy with mugwort pollen allergoid reduce bradykinin release into the nasal fluid (United States)

    Grzanka, Alicja; Jawor, Barbara; Czecior, Eugeniusz


    Introduction A pathomechanism of allergic rhinitis is complex. A neurogenic mechanism seems to play a significant role in this phenomenon. Aim The evaluation of influence of specific immunotherapy of mugwort pollen allergic patients on the bradykinin concentration in the nasal lavage fluid. Material and methods The study included 22 seasonal allergic rhinitis patients. Thirty persons with monovalent allergy to mugwort pollen, confirmed with skin prick tests and allergen-specific immunoglobulin E, underwent a 3-year-long allergen immunotherapy with the mugwort extract (Allergovit, Allergopharma, Germany). The control group was composed of 9 persons with polyvalent sensitivity to pollen, who were treated with pharmacotherapy. Before the allergen-specific immunotherapy (AIT) and in subsequent years before the pollen seasons, a provocation allergen test with the mugwort extract was performed, together with collection of nasal fluids, where bradykinin concentration was determined according to Proud method. Results There were similar levels of bradykinin in both groups at baseline prior to therapy (AIT group: 584.0 ±87.2 vs. controls 606.3 ±106.5 pg/ml) and changes after allergen challenge 1112.4 ±334.8 vs. 1013.3 ±305.9 pg/ml as well. The bradykinin concentration in nasal lavage fluid after mugwort challenge in 1 year was lower in the AIT group (824.1 ±184.2 pg/ml vs. 1000.4 ±411.5 pg/l; p < 005) with a further significant decrease after the 2nd and 3rd year of specific immunotherapy. Significant reduction of symptoms and medications use was observed in hyposensitized patients. Conclusions A decreased level of bradykinin as a result of AIT suggests that some of the symptomatic benefits of AIT may be related to the reduced release of bradykinin into nasal secretions. These values correlate with clinical improvement within the course of treatment. PMID:27605897

  9. [Treatment of drugs-associated non-hereditary angioedema mediated by bradykinin]. (United States)

    Muller, Yannick; Harr, Thomas


    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.

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

    Institute of Scientific and Technical Information of China (English)


    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.

  11. Enzymatic assays for the diagnosis of bradykinin-dependent angioedema.

    Directory of Open Access Journals (Sweden)

    Federica Defendi

    Full Text Available BACKGROUND: The kinins (primarily bradykinin, BK represent the mediators responsible for local increase of vascular permeability in hereditary angioedema (HAE, HAE I-II associated with alterations of the SERPING1 gene and HAE with normal C1-Inhibitor function (HAE-nC1INH. Besides C1-Inhibitor function and concentration, no biological assay of kinin metabolism is actually available to help physicians for the diagnosis of angioedema (AE. We describe enzymatic tests on the plasma for diagnosis of BK-dependent AE. METHODS: The plasma amidase assays are performed using the Pro-Phe-Arg-p-nitroanilide peptide substrate to evaluate the spontaneous amidase activity and the proenzyme activation. We analyzed data of 872 patients presenting with BK-dependent AE or BK-unrelated diseases, compared to 303 controls. Anti-high MW kininogen (HK immunoblot was achieved to confirm HK cleavage in exemplary samples. Reproducibility, repeatability, limit of blank, limit of detection, precision, linearity and receiver operating characteristics (ROC were used to calculate the diagnostic performance of the assays. RESULTS: Spontaneous amidase activity was significantly increased in all BK-dependent AE, associated with the acute phase of disease in HAE-nC1INH, but preserved in BK-unrelated disorders. The increase of the amidase activity was associated to HK proteolysis, indicating its relevance to identify kininogenase activity. The oestrogens, known for precipitating AE episodes, were found as triggers of enzymatic activity. Calculations from ROC curves gave the optimum diagnostic cut-off for women (9.3 nmol⋅min(-1⋅mL(-1, area under curve [AUC] 92.1%, sensitivity 80.0%, and specificity 90.1% and for men (6.6 nmol·min(-1⋅mL(-1, AUC 91.0%, sensitivity 87.0% and specificity 81.2%. CONCLUSION: The amidase assay represents a diagnostic tool to help physicians in the decision to distinguish between BK-related and -unrelated AE.

  12. TRPC3 is involved in flow- and bradykinin-induced vasodilation in rat small mesenteric arteries

    Institute of Scientific and Technical Information of China (English)

    Cui-ling LIU; Yu HUANG; Ching-yuen NGAI; Yuk-ki LEUNG; Xiao-qiang YAO


    Aim: To test the possible involvement of TRPC3 in agonist-induced relaxation and flow-induced vasodilation in rat small mesenteric arteries. Methods: Male Sprague-Dawley rats were used in the present study. After 72 h-treatment of antisense oligo via tail vein injection, isometric tension and isobaric diameter measurement were carried out with isolated mesenteric artery segments by using either a Pressure Myograph or a Multi Myograph system. Endothelial [Ca2+]i changes were measured with a MetaFluor imaging system in response to flow or to 30 nmol/L bradykinin. Results: Immunohistochemical study showed that the 72 h-treatment of antisense oligo via tail vein injection markedly decreased the TRPC3 expression in mesenteric arteries, indicating the effectiveness of the antisense oligo. Isometric tension and isobaric diameter measurement showed that, although the antisense oligo treatment did not affect histamine-, ATP-, and CPA-induced relaxation, it did reduce the magnitude of flow-induced vasodilation by approximately 13% and decreased bradykinin-induced vascular relaxation with its EC50 value raised by nearly 3-fold. Endothelial [Ca2+]i measurement revealed that treatment of the arteries with antisense oligos significantly attenuated the magnitude of endothelial [Ca2+]i rise in response to flow and to 30 nmol/L bradykinin. Conclusion: The results suggest that TRPC3 is involved in flow- and bradykinin-induced vasodilation in rat small mesenteric arteries probably by mediating the Ca2+ influx into endothelial cells.

  13. ACE mediates ventilator-induced lung injury in rats via angiotensin II but not bradykinin

    NARCIS (Netherlands)

    R.M. Wösten-van Asperen; R. Lutter (Rene); J.J. Haitsma; M.P. Merkus; J.B. van Woensel; C.M. van der Loos; S. Florquin (Sandrine); B.F. Lachmann (Burkhard); A.P. Bos (Albert)


    textabstractVentilator-induced lung injury is characterised by inflammation and apoptosis, but the underlying mechanisms are poorly understood. The present study proposed a role for angiotensin-converting enzyme (ACE) via angiotensin II (Ang II) and/or bradykinin in acute lung injury. The authors as

  14. A novel assay to diagnose hereditary angioedema utilizing inhibition of bradykinin-forming enzymes

    DEFF Research Database (Denmark)

    Joseph, Kusumam; Bains, Sonia; Tholanikunnel, Baby G


    BACKGROUND: Hereditary angioedema types I and II are caused by a functional deficiency of C1 inhibitor (C1-INH) leading to overproduction of bradykinin. The current functional diagnostic assays employ inhibition of activated C1s, however, an alternative, more physiologic method, is desirable...

  15. Bradykinin or acetylcholine as vasodilators to test endothelial venous function in healthy subjects

    Directory of Open Access Journals (Sweden)

    Eneida R. Rabelo


    Full Text Available INTRODUCTION: The evaluation of endothelial function has been performed in the arterial bed, but recently evaluation within the venous system has also been explored. Endothelial function studies employ different drugs that act as endothelium-dependent vasodilatory response inductors. OBJECTIVES: The aim of this study is to compare the endothelium-dependent venous vasodilator response mediated by either acetylcholine or bradykinin in healthy volunteers. METHODS AND RESULTS: Changes in vein diameter after phenylephrine-induced venoconstriction were measured to compare venodilation induced by acetylcholine or bradykinin (linear variable differential transformer dorsal hand vein technique. We studied 23 healthy volunteers; 31% were male, and the subject had a mean age of 33 ± 8 years and a mean body mass index of 23 ± 2 kg/m². The maximum endothelium-dependent venodilation was similar for both drugs (p = 0.13, as well as the mean responses for each dose of both drugs (r = 0.96. The maximum responses to acetylcholine and bradykinin also had good agreement. CONCLUSION: There were no differences between acetylcholine and bradykinin as venodilators in this endothelial venous function investigation.

  16. Marketing Optimization for B2B Market


    Kaynova Tatyana V.


    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.

  17. Ephrin-B2 and EphB2 regulation of astrocyte-meningeal fibroblast interactions in response to spinal cord lesions in adult rats. (United States)

    Bundesen, Liza Q; Scheel, Tracy Aber; Bregman, Barbara S; Kromer, Lawrence F


    The present study provides the first evidence that signaling occurs between B-ephrins and EphB receptors in the adult CNS in response to injury. Specifically, our combined histological and biochemical data indicate that two members of the B-class of ephrins and Eph receptors, ephrin-B2 and EphB2, are expressed by astrocytes and meningeal fibroblasts, respectively, in the adult spinal cord. In response to thoracic spinal cord transection lesions, ephrin-B2 and EphB2 protein levels exhibit an initial decrease (1 d after lesion), followed by a significant increase by day 14. Immunohistochemical data indicate that ephrin-B2 is expressed by reactive CNS astrocytes, and EphB2 is present on fibroblasts invading the lesion site from the adjacent meninges. During the first 3 d after injury, there is intermingling of ephrin-B2-expressing reactive astrocytes at the lesion surface with EphB2-containing fibroblasts that is concurrent with bidirectional activation (phosphorylation) of ephrin-B2 and EphB2. By 7 d, both cell types are establishing restricted cellular domains containing dense networks of cells and interweaving processes. This astroglial-meningeal fibroblast scar is fully developed by day 14 when there is strict segregation of ephrin-B2-expressing astrocytes from EphB2-positive meningeal fibroblasts. These morphological changes are concomitant with a simultaneous decrease in ephrin-B2 and EphB2 activation. These observations provide strong evidence that cell contact-mediated bidirectional signaling between ephrin-B2 on reactive astrocytes and EphB2 on meningeal fibroblasts is an early event in the cellular cascades that result in the development of the glial scar and the exclusion of meningeal fibroblasts from the injured spinal cord.

  18. 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 potentialanti-inflammatory effe... Epub 2007 Jun 27. (.png) (.svg) (.html) (.csml) Show Multifunctional effects of bradykinin on glial cells i...n relation to potentialanti-inflammatory effects. PubmedID 17669557 Title Multifunctional effects... of bradykinin on glial cells in relation to potentialanti-inflammatory effects. Authors Nod...cts. Noda M, Sasaki K, Ifuku M, Wada K. Neurochem Int. 2007 Jul-Sep;51(2-4):185-91.

  19. The Vaporization of B2O3(l) to B2O3(g) and B2O2(g) (United States)

    Jacobson, Nathan S.; Myers, Dwight L.


    The vaporization of B2O3 in a reducing environment leads to formation of both B2O3(g) and B2O2(g). While formation of B2O3(g) is well understood, many questions about the formation of B2O2(g) remain. Previous studies using B(s) + B2O3(l) have led to inconsistent thermodynamic data. In this study, it was found that after heating, B(s) and B2O3(l) appear to separate and variations in contact area likely led to the inconsistent vapor pressures of B2O2(g). To circumvent this problem, an activity of boron is fixed with a two-phase mixture of FeB and Fe2B. Both second and third law enthalpies of formation were measured for B2O2(g) and B2O3(g). From these the enthalpies of formation at 298.15 K are calculated to be -479.9 +/- 41.5 kJ/mol for B2O2(g) and -833.4 +/- 13.1 kJ/mol for B2O3(g). Ab initio calculations to determine the enthalpies of formation of B2O2(g) and B2O3(g) were conducted using the W1BD composite method and show good agreement with the experimental values.

  20. Local radiotherapy increases the level of autoantibodies to ribosomal P0 protein but not to heat shock proteins, extracellular matrix molecules and EGFR/ErbB2 receptors in prostate cancer patients. (United States)

    Ingrosso, Gianluca; Fantini, Massimo; Nardi, Alessandra; Benvenuto, Monica; Sacchetti, Pamela; Masuelli, Laura; Ponti, Elisabetta; Frajese, Giovanni Vanni; Lista, Florigio; Schillaci, Orazio; Santoni, Riccardo; Modesti, Andrea; Bei, Roberto


    Prostate cancer is a common cancer among men in developed countries. Although hormonotherapy and radiotherapy (RT) represent valid therapies for prostate cancer treatment, novel immunological approaches have been explored. The development of clinical trials employing cancer vaccines has indicated that immune response to tumor antigens can be boosted and that vaccine administration can improve patient survival. Immune response to tumor antigens could also be enhanced after standard therapies. In the present study, we determined the occurrence of antibodies to extracellular matrix (ECM) molecules, heat shock protein (HSP), ribosomal P0 protein, EGFR, ErbB2 and prostate-specific antigen (PSA) in 35 prostate cancer patients prior to and following local RT and hormonotherapy. We demonstrated that immunity to P0, ECM molecules [collagens (C) CI, CIII, CV, fibronectin (FN) and laminin (LM)] and to HSP90 was associated with malignancy in untreated patients. None of the patient sera showed antibodies to EGFR, while 2 and 1 patients showed reactivity to ErbB2 and PSA, respectively. We also demonstrated that 8 months after therapy the IgG serum levels to CI, CIII, FN and HSP90 significantly decreased. Conversely, the level of P0 autoantibodies increased after therapy in 10 patients. Five of the 10 patients with increased levels of P0 autoantibodies were treated with RT plus hormonotherapy. Treatment of patients did not change the levels of antibodies against EGFR, ErbB2 and PSA. Our results indicated that the modification of antibody level to self molecules after standard treatment of prostate cancer patients is influenced by the type of antigen. Ribosomal P0 protein appears to be a high immunogenic antigen and its immunogenicity increases following RT. In addition, 10 patients with increased levels of autoantibodies to P0 showed PSA mean levels lower than the remaining 25 patients at 18 months. This study may contribute to a better understanding of the

  1. 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


    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.

  2. 32 CFR 806b.2 - Basic guidelines. (United States)


    ... 32 National Defense 6 2010-07-01 2010-07-01 false Basic guidelines. 806b.2 Section 806b.2 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE ADMINISTRATION PRIVACY ACT PROGRAM Overview of the Privacy Act Program § 806b.2 Basic guidelines. This part implements the Privacy Act of...

  3. 18 CFR 1b.2 - Scope. (United States)


    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Scope. 1b.2 Section 1b.2 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.2 Scope. This part applies to...

  4. Effect of Jingqianping Granules and Jingqianshu Granules on Expression of Hypothalamic γ-Aminobutyric Acid B2 Receptor in Emotional Rats Models of Anger-out and Anger-in%经前平和经前舒颗粒对愤怒郁怒情绪模型大鼠下丘脑γ氨基丁酸B2受体表达的影响

    Institute of Scientific and Technical Information of China (English)

    姜英凤; 薛玲


    Objective To investigate the expression of "γ-aminobutyric acid B2 receptor (GABABR2)in rats models of anger-out and anger-in, and to explore the intervention mechanism of liver-regulating compound Formulas of Jingqianping Granule and Jingqianshu Granules. Methods The emotional models of anger-out and anger-in were induced in rats by social isolation plus resident-intruder. We analyzed the expression of hypothalamic GABAbR2 by Western blot and RT-PCR methods. Results The mRNA and protein expression levels of hypothalamic GABAbR2 in model rats were decreased when compared with that in the normal control group (P < 0.05-0.01), and the decrease of GABABR2 expression in anger-out model group was more significant than that in anger-in model group. Compared with the model groups, mRNA and protein expression levels of hypothalamic GABArR2 were increased in the medication groups to various degrees. Conclusion The decrease of hypothalamic GABAbR2 expression is one of common e- motional mechanisms in rats with with anger-out and anger-in emotion, and Jingqianping Granules and Jingqianshu Granules can up-regulate the GABAbR2 expression level.%目的 探索愤怒、郁怒情绪与γ氨基丁酸B2受体(GABABR2)的关系,以及调肝方药经前平颗粒和经前舒颗粒的中枢干预机制.方法采用居住入侵和社会隔离的方法复制愤怒、郁怒情绪大鼠模型,用RT-PCR和Western Blot的方法检测GABARR2 mRNA和蛋白的表达差异.结果与正常对照组相比,愤怒、郁怒情绪模型大鼠下丘脑GABABR2 mRNA水平和蛋白水平均明显下降(P<0.01~0.05),而且愤怒模型组的降低程度明显大于郁怒模型组.与各模型组相比,各给药组GABABR2 mRNA水平和蛋白水平均有不同程度的升高.结论大鼠下丘脑GABABR2表达降低可能是影响大鼠愤怒和郁怒情绪的重要共性机制之一;中药经前平和经前舒颗粒对GABABR2表达异常变化具有调节作用.

  5. Efficient generation of B2m-null pigs via injection of zygote with TALENs (United States)

    Wang, Yong; Du, Yinan; Zhou, Xiaoyang; Wang, Lulu; Li, Jian; Wang, Fengchao; Huang, Zhengen; Huang, Xingxu; Wei, Hong


    Donor major histocompatibility complex class I (MHC I) molecules are the main targets of the host immune response after organ allotransplantation. Whether and how MHC I-deficiency of pig donor tissues affects rejection after xenotransplantation has not been assessed. Beta2-microglobulin (B2M) is indispensable for the assembly of MHC I receptors and therefore provides an effective target to disrupt cell surface MHC I expression. Here, we report the one-step generation of mutant pigs with targeted disruptions in B2m by injection of porcine zygotes with B2m exon 2-specific TALENs. After germline transmission of mutant B2m alleles, we obtained F1 pigs with biallelic B2m frameshift mutations. F1 pigs lacked detectable B2M expression in tissues derived from the three germ layers, and their lymphocytes were devoid of MHC I surface receptors. Skin grafts from B2M deficient pigs exhibited remarkably prolonged survival on xenogeneic wounds compared to tissues of non-mutant littermates. Mutant founder pigs with bi-allelic disruption in B2m and B2M deficient F1 offspring did not display visible abnormalities, suggesting that pigs are tolerant to B2M deficiency. In summary, we show the efficient generation of pigs with germline mutations in B2m, and demonstrate a beneficial effect of donor MHC I-deficiency on xenotransplantation. PMID:27982048

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

    Directory of Open Access Journals (Sweden)

    Schillaci Roxana


    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusions 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.

  7. Lattice dynamical and thermodynamical properties of ReB2, RuB2, and OsB2 compounds in the ReB2 structure

    Institute of Scientific and Technical Information of China (English)

    E. Deligoz; K. Colakoglu; Y. O. Ciftci


    Structural and lattice dynamical properties of ReB2,RuB2,and OsB2 in the ReB2 structure are studied in the framework of density functional theory within the generalized gradient approximation.The present results show that these compounds are dynamically stable for the considered structure.The temperature-dependent behaviors of thermodynamical properties such as internal energy,free energy,entropy,and heat capacity are also preented. The obtained results are in good agreement with the available experimental and theoretical data.

  8. Vasopeptidase-activated latent ligands of the histamine receptor-1. (United States)

    Gera, Lajos; Roy, Caroline; Charest-Morin, Xavier; Marceau, François


    Whether peptidases present in vascular cells can activate prodrugs active on vascular cells has been tested with 2 potential latent ligands of the histamine H1 receptor (H1R). First, a peptide consisting of the antihistamine cetirizine (CTZ) condensed at the N-terminus of ε-aminocaproyl-bradykinin (εACA-BK) was evaluated for an antihistamine activity that could be revealed by degradation of the peptide part of the molecule. CTZ-εACA-BK had a submicromolar affinity for the BK B2 receptor (B2R; IC50 of 590 nM, [(3)H]BK binding competition), but a non-negligible affinity for the human H1 receptor (H1R; IC50 of 11 μM for [(3)H]pyrilamine binding). In the human isolated umbilical vein, a system where both endogenous B2R and H1R mediate strong contractions, CTZ-εACA-BK exerted mild antagonist effects on histamine-induced contraction that were not modified by omapatrilat or by a B2R antagonist that prevents endocytosis of the BK conjugate. Cells expressing recombinant ACE or B2R incubated with CTZ-εACA-BK did not release a competitor of [(3)H]pyrilamine binding to H1Rs. Thus, there is no evidence that CTZ-εACA-BK can release free cetirizine in biological environments. The second prodrug was a blocked agonist, L-alanyl-histamine, potentially activated by aminopeptidase N (APN). This compound did not compete for [(3)H]pyrilamine binding to H1Rs. The human umbilical vein contractility assay responded to L-alanyl-histamine (EC50 54.7 μM), but the APN inhibitor amastatin massively (17-fold) reduced its apparent potency. Amastatin did not influence the potency of histamine as a contractile agent. One of the 2 tested latent H1R ligands, L-alanyl-histamine, supported the feasibility of pro-drug activation by vascular ectopeptidases.

  9. Role of Erbin in ErbB2-dependent breast tumor growth. (United States)

    Tao, Yanmei; Shen, Chengyong; Luo, Shiwen; Traoré, Wilfried; Marchetto, Sylvie; Santoni, Marie-Josée; Xu, Linlin; Wu, Biao; Shi, Chao; Mei, Jinghong; Bates, Ryan; Liu, Xihui; Zhao, Kai; Xiong, Wen-Cheng; Borg, Jean-Paul; Mei, Lin


    ErbB2 (v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2), a receptor tyrosine kinase of the ErbB family, is overexpressed in around 25% of breast cancers. In addition to forming a heterodimer with other ErbB receptors in response to ligand stimulation, ErbB2 can be activated in a ligand-independent manner. We report here that Erbin, an ErbB2-interacting protein that was thought to act as an antitumor factor, is specifically expressed in mammary luminal epithelial cells and facilitates ErbB2-dependent proliferation of breast cancer cells and tumorigenesis in MMTV-neu transgenic mice. Disruption of their interaction decreases ErbB2-dependent proliferation, and deletion of the PDZ domain in Erbin hinders ErbB2-dependent tumor development in MMTV-neu mice. Mechanistically, Erbin forms a complex with ErbB2, promotes its interaction with the chaperon protein HSP90, and thus prevents its degradation. Finally, ErbB2 and Erbin expression correlates in human breast tumor tissues. Together, these observations establish Erbin as an ErbB2 regulator for breast tumor formation and progression.

  10. 12 CFR 264b.2 - Definitions. (United States)


    ... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Definitions. 264b.2 Section 264b.2 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM RULES... such. (c) Gift means a tangible or intangible present (other than a decoration) tendered by,...

  11. 18 CFR 3b.2 - Definitions. (United States)


    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Definitions. 3b.2 Section 3b.2 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF IDENTIFIABLE...

  12. Inhibition of ErbB-2 Mitogenic and Transforming Activity by RALT, a Mitogen-Induced Signal Transducer Which Binds to the ErbB-2 Kinase Domain† (United States)

    Fiorentino, Loredana; Pertica, Chiara; Fiorini, Monia; Talora, Claudio; Crescenzi, Marco; Castellani, Loriana; Alemà, Stefano; Benedetti, Piero; Segatto, Oreste


    The product of rat gene 33 was identified as an ErbB-2-interacting protein in a two-hybrid screen employing the ErbB-2 juxtamembrane and kinase domains as bait. This interaction was reproduced in vitro with a glutathione S-transferase fusion protein spanning positions 282 to 395 of the 459-residue gene 33 protein. Activation of ErbB-2 catalytic function was required for ErbB-2–gene 33 physical interaction in living cells, whereas ErbB-2 autophosphorylation was dispensable. Expression of gene 33 protein was absent in growth-arrested NIH 3T3 fibroblasts but was induced within 60 to 90 min of serum stimulation or activation of the ErbB-2 kinase and decreased sharply upon entry into S phase. New differentiation factor stimulation of mitogen-deprived mammary epithelial cells also caused accumulation of gene 33 protein, which could be found in a complex with ErbB-2. Overexpression of gene 33 protein in mouse fibroblasts inhibited (i) cell proliferation driven by ErbB-2 but not by serum, (ii) cell transformation induced by ErbB-2 but not by Ras or Src, and (iii) sustained activation of ERK 1 and 2 by ErbB-2 but not by serum. The gene 33 protein may convey inhibitory signals downstream to ErbB-2 by virtue of its association with SH3-containing proteins, including GRB-2, which was found to associate with gene 33 protein in living cells. These data indicate that the gene 33 protein is a feedback inhibitor of ErbB-2 mitogenic function and a suppressor of ErbB-2 oncogenic activity. We propose that the gene 33 protein be renamed with the acronym RALT (receptor-associated late transducer). PMID:11003669

  13. Inhibition of ErbB-2 mitogenic and transforming activity by RALT, a mitogen-induced signal transducer which binds to the ErbB-2 kinase domain. (United States)

    Fiorentino, L; Pertica, C; Fiorini, M; Talora, C; Crescenzi, M; Castellani, L; Alemà, S; Benedetti, P; Segatto, O


    The product of rat gene 33 was identified as an ErbB-2-interacting protein in a two-hybrid screen employing the ErbB-2 juxtamembrane and kinase domains as bait. This interaction was reproduced in vitro with a glutathione S-transferase fusion protein spanning positions 282 to 395 of the 459-residue gene 33 protein. Activation of ErbB-2 catalytic function was required for ErbB-2-gene 33 physical interaction in living cells, whereas ErbB-2 autophosphorylation was dispensable. Expression of gene 33 protein was absent in growth-arrested NIH 3T3 fibroblasts but was induced within 60 to 90 min of serum stimulation or activation of the ErbB-2 kinase and decreased sharply upon entry into S phase. New differentiation factor stimulation of mitogen-deprived mammary epithelial cells also caused accumulation of gene 33 protein, which could be found in a complex with ErbB-2. Overexpression of gene 33 protein in mouse fibroblasts inhibited (i) cell proliferation driven by ErbB-2 but not by serum, (ii) cell transformation induced by ErbB-2 but not by Ras or Src, and (iii) sustained activation of ERK 1 and 2 by ErbB-2 but not by serum. The gene 33 protein may convey inhibitory signals downstream to ErbB-2 by virtue of its association with SH3-containing proteins, including GRB-2, which was found to associate with gene 33 protein in living cells. These data indicate that the gene 33 protein is a feedback inhibitor of ErbB-2 mitogenic function and a suppressor of ErbB-2 oncogenic activity. We propose that the gene 33 protein be renamed with the acronym RALT (receptor-associated late transducer).

  14. Photo-activated psoralen binds the ErbB2 catalytic kinase domain, blocking ErbB2 signaling and triggering tumor cell apoptosis.

    Directory of Open Access Journals (Sweden)

    Wenle Xia

    Full Text Available Photo-activation of psoralen with UVA irradiation, referred to as PUVA, is used in the treatment of proliferative skin disorders. The anti-proliferative effects of PUVA have been largely attributed to psoralen intercalation of DNA, which upon UV treatment, triggers the formation of interstrand DNA crosslinks (ICL that inhibit transcription and DNA replication. Here, we show that PUVA exerts antitumor effects in models of human breast cancer that overexpress the ErbB2 receptor tyrosine kinase oncogene, through a new mechanism. Independent of ICL formation, the antitumor effects of PUVA in ErbB2+ breast cancer models can instead be mediated through inhibition of ErbB2 activation and signaling. Using a mass spectroscopy-based approach, we show for the first time that photo-activated 8MOP (8-methoxypsoralen interacts with the ErbB2 catalytic autokinase domain. Furthermore, PUVA can reverse therapeutic resistance to lapatinib and other ErbB2 targeted therapies, including resistance mediated via expression of a phosphorylated, truncated form of ErbB2 (p85(ErbB2 that is preferentially expressed in tumor cell nuclei. Current ErbB2 targeted therapies, small molecule kinase inhibitors or antibodies, do not block the phosphorylated, activated state of p85(ErbB2. Here we show that PUVA reduced p85(ErbB2 phosphorylation leading to tumor cell apoptosis. Thus, in addition to its effects on DNA and the formation of ICL, PUVA represents a novel ErbB2 targeted therapy for the treatment of ErbB2+ breast cancers, including those that have developed resistance to other ErbB2 targeted therapies.

  15. 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


    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

  16. Effects of the intra-arterial injection of bradykinin into the limbs, upon the activity of mesencephalic reticular units. (United States)

    Lombard, M C; Guilbaud, G; Besson, J M


    The changes in firing rate of mesencephalic reticular units after intra-arterial injection into the limbs of a potent nociceptive agent, bradykinin, were studied in cats (unanesthetized, immobilized with flaxedil and hyperventilated). 30 per cent of the d35 studied cells were affected, 56 per cent were excited, 23 per cent inhibited and 5 per cent had mixed effects. Among the 75 excited cells, the activation of 16 of them seemed to related to the arousa- processes (group A); for 56 cells the increase seemed dire-tly dependent on the nociceptive stimulation itself (group B). The changes of firing rate were repruducible; their latencies and durations were of the same order as the latencies and duration of the nociceptive reactions and painful sensation s, which have been obtained in animals and men after bradykinin injections. The modifications induced by bradykinin administration were suppressed by Ketamin and Thiopental.

  17. Exogenous Bradykinin Inhibits Tissue Factor Induction and Deep Vein Thrombosis via Activating the eNOS/Phosphoinositide 3-Kinase/Akt Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Ruolan Dong


    Full Text Available Background/Aims: Bradykinin has been shown to exert a variety of protective effects against vascular injury, and to reduce the levels of several factors involved in the coagulation cascade. A key determinant of thrombin generation is tissue factor (TF. However, whether bradykinin can regulate TF expression remains to be investigated. Methods: To study the effect of bradykinin on TF expression, we used Lipopolysaccharides (LPS to induce TF expression in human umbilical vein endothelial cells and monocytes. Transcript levels were determined by RT-PCR, protein abundance by Western blotting. In the in vivo study, bradykinin and equal saline were intraperitoneally injected into mice for three days ahead of inferior cava vein ligation that we took to induce thrombus formation, after which bradykinin and saline were injected for another two days. Eventually, the mice were sacrificed and tissues were harvested for tests. Results: Exogenous bradykinin markedly inhibited TF expression in mRNA and protein level induced by LPS in a dose-dependent manner. Moreover, the NO synthase antagonist L-NAME and PI3K inhibitor LY294002 dramatically abolished the inhibitory effects of bradykinin on tissue factor expression. PI3K/Akt signaling pathway activation induced by bradykinin administration reduced the activity of GSK-3ß and MAPK, and reduced NF-κB level in the nucleus, thereby inhibiting TF expression. Consistent with this, intraperitoneal injection of C57/BL6 mice with bradykinin also inhibited the thrombus formation induced by ligation of inferior vena cava. Conclusion: Bradykinin suppressed TF protein expression in human umbilical vein endothelial cells and monocytes in vitro; in line with this, it inhibits thrombus formation induced by ligation of inferior vena cava in vivo.

  18. Nociceptor-expressed ephrin-B2 regulates inflammatory and neuropathic pain

    Directory of Open Access Journals (Sweden)

    Kullander Klas


    Full Text Available Abstract Background EphB receptors and their ephrin-B ligands play an important role in nervous system development, as well as synapse formation and plasticity in the adult brain. Recent studies show that intrathecal treatment with EphB-receptor activator ephrinB2-Fc induced thermal hyperalgesia and mechanical allodynia in rat, indicating that ephrin-B2 in small dorsal root ganglia (DRG neurons and EphB receptors in the spinal cord modulate pain processing. To examine the role of ephrin-B2 in peripheral pain pathways, we deleted ephrin-B2 in Nav1.8+ nociceptive sensory neurons with the Cre-loxP system. Sensory neuron numbers and terminals were examined using neuronal makers. Pain behavior in acute, inflammatory and neuropathic pain models was assessed in the ephrin-B2 conditional knockout (CKO mice. We also investigated the c-Fos expression and NMDA receptor NR2B phosphorylation in ephrin-B2 CKO mice and littermate controls. Results The ephrin-B2 CKO mice were healthy with no sensory neuron loss. However, pain-related behavior was substantially altered. Although acute pain behavior and motor co-ordination were normal, inflammatory pain was attenuated in ephrin-B2 mutant mice. Complete Freund's adjuvant (CFA-induced mechanical hyperalgesia was halved. Formalin-induced pain behavior was attenuated in the second phase, and this correlated with diminished tyrosine phosphorylation of N-methyl-D-aspartic acid (NMDA receptor subunit NR2B in the dorsal horn. Thermal hyperalgesia and mechanical allodynia were significantly reduced in the Seltzer model of neuropathic pain. Conclusions Presynaptic ephrin-B2 expression thus plays an important role in regulating inflammatory pain through the regulation of synaptic plasticity in the dorsal horn and is also involved in the pathogenesis of some types of neuropathic pain.

  19. LINGO-1 regulates oligodendrocyte differentiation by inhibiting ErbB2 translocation and activation in lipid rafts. (United States)

    Lee, Xinhua; Shao, Zhaohui; Sheng, Guoqing; Pepinsky, Blake; Mi, Sha


    Oligodendrocyte differentiation is negatively regulated by LINGO-1 and positively regulated by the ErbB2 receptor tyrosine kinase. In wild-type oligodendrocytes, inhibition of ErbB2 blocks differentiation, whereas activation of ErbB2 promotes differentiation. In LINGO-1(-/-) oligodendrocytes, inhibition of ErbB2 blocks oligodendrocyte differentiation; whereas activation of ErbB2 does not enhance differentiation. Biological and biochemical evidence showing that LINGO-1 can directly bind to ErbB2, block ErbB2 translocation into lipid rafts, and inhibit its phosphorylation for activation. The study demonstrates a novel regulatory mechanism of ErbB2 function whereby LINGO-1 suppresses oligodendrocyte differentiation by inhibiting ErbB2 translocation and activation in lipid rafts.

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

    Directory of Open Access Journals (Sweden)

    Carvalho K.M.


    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 and angiotensin-converting enzyme (EC, 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.

  1. 蛇毒舒缓激肽增强肽%Snake venom bradykinin potentiating peptide

    Institute of Scientific and Technical Information of China (English)

    李旭慧; 权燕敏; 吴晓莎; 杨章民


    舒缓激肽增强肽(bradykinin potentiating peptide,BPP)是广泛分布于蝰科(主要是蝮亚科)蛇毒中的一类小分子生物活性肽.BPP具有增强舒缓激肽以及抑制血管紧张素Ⅰ转化酶(angiotensin-Ⅰ converting enzyme,ACE)活性的双重毒理学作用,是造成被毒蛇咬伤时血压骤降的主要组分,也是降压药开博通(Captopril)的天然模式分子.本文简要综述了蛇毒BPP分布与种类、结构和生物学功能等方面的研究进展.%Bradykinin potentiating peptides (BPPs) represent a class of short chain peptides with multiple biological activities,which are distributed widely in the snake venoms of Viperidae (mainly Crotalinae).BPPs can potentiate the actions of bradykinin,and can inhibit the activity of angiotensin-Ⅰ converting enzyme (peptidyl-dipeptidase A) 1 (ACE).The cooperative effects lead to lower the blood pressure in snakebite envenomation,and make it possible to be a natural lead for the anti-hypertension drug (Captopril) design.Here,we briefly review the recent advances in snake venom BPPs,including their distribution,variety,structure and biological functions.

  2. Main: B2GMAUX28 [PLACE

    Lifescience Database Archive (English)

    Full Text Available B2GMAUX28 S000325 7-Sep-2000 (last modified) seki B2; DNase I protected sequence fo...und in the soybean (G.m.) auxin responsive gene, Aux28, promoter; Located between -310 and -301; Contains a ...TGACGACA sequence which is similar to TGACGT/C sequence found in Ocs, CaMV35S and histone H3 promoter; Contains as-1 motif; auxin; Aux28; as-1; soybean (Glycine max) CTTGTCGTCA ...

  3. Doping-induced superconductivity of ZrB2 and HfB2 (United States)

    Barbero, N.; Shiroka, T.; Delley, B.; Grant, T.; Machado, A. Â. J. Â. S.; Fisk, Z.; Ott, H.-R.; Mesot, J.


    Unlike the widely studied s -type two-gap superconductor MgB2, the chemically similar compounds ZrB2 and HfB2 do not superconduct above 1 K. Yet it has been shown that small amounts of self or extrinsic doping (in particular with vanadium), can induce superconductivity in these materials. Based on results of different macroscopic and microscopic measurements, including magnetometry, nuclear magnetic resonance (NMR), resistivity, and muon-spin rotation (μ+SR ), we present a comparative study of Zr0.96V0.04B2 and Hf0.97V0.03B2 . Their key magnetic and superconducting features are determined and the results are considered within the theoretical framework of multiband superconductivity proposed for MgB2. Detailed Fermi surface (FS) and electronic structure calculations reveal the difference between MgB2 and transition-metal diborides.

  4. Effect of forskolin on alterations of vascular permeability induced with bradykinin, prostaglandin E1, adenosine, histamine and carrageenin in rats. (United States)

    Sugio, K; Daly, J W


    The effect of the diterpene forskolin on vascular permeability alone and in combination with bradykinin, prostaglandin E1, adenosine or histamine has been investigated in rats. Vascular permeability in rat skin was measured using [125I]-labelled bovine serum albumin ([125I]BSA) as a tracer. In addition, the effect of forskolin on footpad edema induced by the injection of a mixture of 2% carrageenin was determined. Forskolin caused a marked potentiation of the increase in vascular permeability in rat skin elicited by the intradermal injection of histamine or bradykinin. However, forskolin caused a significant suppression of the prostaglandin E1-induced vascular permeability response and at a low concentration suppressed the response to adenosine. Forskolin greatly potentiated the footpad edema induced with carrageenin in rats. Intravenous administration of the enzyme bromelain, which reduces plasma kininogen levels, inhibited the footpad edema induced with carrageenin or with a mixture of carrageenin and forskolin. Parenteral administration of a prostaglandin synthetase inhibitor, indomethacin, suppressed the footpad edema induced with carrageenin, but did not inhibit the footpad edema induced with a mixture of carrageenin and forskolin. An antihistamine, cyproheptadine, had no effect on carrageenin-induced footpad edema either in the presence or absence of forskolin. These results suggest that both bradykinin and prostaglandins are essential for the development of carrageenin-induced footpad edema and that bradykinin plays an important role in the potentiative effect of forskolin on footpad edema induced with carrageenin in rats.

  5. Plasmin is a natural trigger for bradykinin production in patients with hereditary angioedema with factor XII mutations

    NARCIS (Netherlands)

    de Maat, Steven; Björkqvist, Jenny; Suffritti, Chiara; Wiesenekker, Chantal P.; Nagtegaal, Willem; Koekman, Arnold; van Dooremalen, Sanne; Pasterkamp, Gerard; de Groot, Philip G.; Cicardi, Marco; Renné, Thomas; Maas, Coen


    BACKGROUND: Patients with angioedema experience unpredictable attacks of tissue swelling in which bradykinin is implicated. Several distinct mutations in Factor XII (FXII) are associated with hereditary angioedema (HAE) in the presence of normal C1 esterase inhibitor activity (FXII-HAE). The underly


    NARCIS (Netherlands)



    In this study, the effect of bradykinin or saline infusion during ischemia and reperfusion on electrical stability, 2 weeks after myocardial infarction, was assessed. Acute myocardial infarction was induced in 21 pigs by a transluminal occlusion of the left coronary artery with a catheter balloon, i

  7. Regulation of ErbB2 localization and function in breast cancer cells by ERM proteins (United States)

    Asp, Nagham; Kvalvaag, Audun; Sandvig, Kirsten; Pust, Sascha


    The ERM protein family is implicated in processes such as signal transduction, protein trafficking, cell proliferation and migration. Consequently, dysregulation of ERM proteins has been described to correlate with carcinogenesis of different cancer types. However, the underlying mechanisms are poorly understood. Here, we demonstrate a novel functional interaction between ERM proteins and the ErbB2 receptor tyrosine kinase in breast cancer cells. We show that the ERM proteins ezrin and radixin are associated with ErbB2 receptors at the plasma membrane, and depletion or functional inhibition of ERM proteins destabilizes the interaction of ErbB2 with ErbB3, Hsp90 and Ebp50. Accompanied by the dissociation of this protein complex, binding of ErbB2 to the ubiquitin-ligase c-Cbl is increased, and ErbB2 becomes dephosphorylated, ubiquitinated and internalized. Furthermore, signaling via Akt- and Erk-mediated pathways is impaired upon ERM inhibition. Finally, interference with ERM functionality leads to receptor degradation and reduced cellular levels of ErbB2 and ErbB3 receptors in breast cancer cells. PMID:27029001

  8. Bradykinin and its gly sup 6 analogue are substrates of cyclophilin: A fluorine-19 magnetization transfer study

    Energy Technology Data Exchange (ETDEWEB)

    London, R.E.; Davis, D.G. (NIEHS, NC (USA)); Vavrek, R.J.; Stewart, J.M. (Univ. of Colorado Health Sciences Center, Denver, CO (USA)); Handschumacher, R.E. (Yale Univ., New Haven, CT (USA))


    Fluorine-19 magnetization transfer experiments have been used to determine the rates of cis/trans isomerization about the X-Pro{sup 7} peptide bond in (p-fluoro-Phe{sup 8})bradykinin and its Gly{sup 6} analogue. The measurements were carried out both prior to and after the addition of cyclophilin, which has recently been shown to have peptidyl-proline cis/trans isomerase activity and is the apparent target enzyme of the immunosuppressive agent cyclosporin A. Magnetization transfer measurements over the temperature range 40-75 {degree}C in the absence of enzyme give activation energies of 22.8 and 23.0 kcal/mol for (p-fluoro-Phe{sup 8})bradykinin and its Gly{sup 6} analogue, respectively. The values for the uncatalyzed cis {r arrow} trans rate constant, k{sub c}, are determined by extrapolation to be 4.8 {times} 10{sup {minus}2} and 2.1 {times} 10{sup {minus}2} s{sup {minus}1} for the two peptides at 25 {degree}C. The enzyme-catalyzed enhancement of the cis/trans interconversion rate was proportional to added cyclophilin concentration and was strongly sequence specific, with bradykinin a much better substrate than (Gly{sup 6})bradykinin. At a peptide concentration of 2.2 mM, the catalytic activity expressed as k{sub c} per micromolar cyclophilin was determined to be 1.2 s{sup {minus}1}/{mu}M for (p-fluoro-Phe{sup 8})bradykinin and 0.13 s{sup {minus}1}/{mu}M for the Gly{sup 6}analogue. The increased cis {r arrow} trans interconversion rates were strongly inhibited by cyclosporin A and the 6-(methylalanine) derivative, which bind to cyclophilin, but not by the 1-(tetrahydrofurfuryl) derivative of cyclosporin that binds weakly.

  9. Superconductivity in MgB2

    Institute of Scientific and Technical Information of China (English)


    In January of 2001 the superconductivity of the compound MgB2 with a critical temperature Tc of up to 39 K was discovered. This Tc is the highest in all intermetallic compound and alloy superconductors. MgB2 has a simple structure and its manufacturing capital cost is lower, therefore it could become a practical superconductor in the future. The recent progress is reviewed here which covers the progress in electronic structure, high Tc mechanism, superconducting parameters (Debye temperature, specific heat coefficient of electron, critical fields, coherent length, penetration depth, energy gap, critical current and relaxation rate of flux). Moreover the issue on power transmission is discussed.

  10. Differential regulation of collagen secretion by kinin receptors in cardiac fibroblast and myofibroblast

    Energy Technology Data Exchange (ETDEWEB)

    Catalán, Mabel; Smolic, Christian [Centro de estudios moleculares de la célula, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile (Chile); Contreras, Ariel [Instituto Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile (Chile); Ayala, Pedro; Olmedo, Ivonne; Copaja, Miguel; Boza, Pía; Vivar, Raúl; Avalos, Yennifer [Centro de estudios moleculares de la célula, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile (Chile); Lavandero, Sergio [Centro de estudios moleculares de la célula, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile (Chile); Instituto Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile (Chile); Department of Internal Medicine (Cardiology Division), University of Texas Southwestern Medical Center, Dallas, TX (United States); Velarde, Victoria [Departamento de Ciencias Fisiológicas, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago (Chile); Díaz-Araya, Guillermo, E-mail: [Centro de estudios moleculares de la célula, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile (Chile)


    Kinins mediate their cellular effects through B1 (B1R) and B2 (B2R) receptors, and the activation of B2R reduces collagen synthesis in cardiac fibroblasts (CF). However, the question of whether B1R and/or B2R have a role in cardiac myofibroblasts remains unanswered. Methods: CF were isolated from neonate rats and myofibroblasts were generated by an 84 h treatment with TGF-β1 (CMF). B1R was evaluated by western blot, immunocytochemistry and radioligand assay; B2R, inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), and cyclooxygenases 1and 2 (COX-1, and COX-2) were evaluated by western blot; intracellular Ca{sup +2} levels were evaluated with Fluo-4AM; collagen secretion was measured in the culture media using the picrosirius red assay kit. Results: B2R, iNOS, COX-1 and low levels of B1R but not eNOS, were detected by western blot in CF. Also, B1R, B2R, and COX-2 but not iNOS, eNOS or COX-1, were detected by western blot in CMF. By immunocytochemistry, our results showed lower intracellular B1R levels in CF and higher B1R levels in CMF, mainly localized on the cell membrane. Additionally, we found B1R only in CMF cellular membrane through radioligand displacement assay. Bradykinin (BK) B2R agonist increased intracellular Ca{sup 2+} levels and reduced collagen secretion both in CF and CMF. These effects were blocked by HOE-140, and inhibited by L-NAME, 1400W and indomethacin. Des-Arg-kallidin (DAKD) B1R agonist did not increase intracellular Ca{sup 2+} levels in CF; however, after preincubation for 1 h with DAKD and re-stimulation with the same agonist, we found a low increase in intracellular Ca{sup 2+} levels. Finally, DAKD increased intracellular Ca{sup 2+} levels and decreased collagen secretion in CMF, being this effect blocked by the B1R antagonist des-Arg9-Leu8-kallidin and indomethacin, but not by L-NAME or 1400 W. Conclusion: B1R, B2R, iNOS and COX-1 were expressed differently between CF and CMF, and collagen secretion was

  11. Salmeterol and cytokines modulate inositol-phosphate signalling in Human airway smooth muscle cells via regulation at the receptor locus

    Directory of Open Access Journals (Sweden)

    Swan Caroline


    Full Text Available Abstract Background Airway hyper-responsiveness (AHR is a key feature of asthma and a causal relationship between airway inflammation and AHR has been identified. The aim of the current study was to clarify the effect of proinflammatory cytokines and asthma medication on primary human airway smooth muscle (ASM inositol phosphate (IPx signalling and define the regulatory loci involved. Methods Primary Human ASM cells were isolated from explants of trachealis muscle from individuals with no history of respiratory disease. The effect of cytokine or asthma medication on histamine or bradykinin induced IPx signalling was assessed by [3H] inositol incorporation. Quantitative Real Time PCR was used to measure mRNA levels of receptors and downstream signalling components. Transcriptional mechanisms were explored using a combination of 5'Rapid Amplification of cDNA Ends (5'RACE and promoter-reporter techniques. Results Treatment of Human ASM cells with IL-13, IFNγ or salmeterol for 24 hours lead to a modest augmentation of histamine induced IPx responses (144.3 +/- 9.3, 126.4 +/- 7.5 and 117.7 +/- 5.2%, p i.e. H1 Histamine Receptor (HRH1, B2 Bradykinin Receptor (BDKRB2, Gαq/11 and PLC-β1 identified that a significant induction of receptor mRNA (>2 fold was a feature of these responses explaining the cytokine and spasmogen specificity. The HRH1 and BDKRB2 promoter regions were mapped in ASM and promoter-reporter analyses identified that salmeterol can induce HRH1 (>2 fold and BDKRB2 (2–5 fold transcription. The effect of cytokines on HRH1 and BDKRB2 promoter-reporter expression suggested a more complex regulation of mRNA expression involving additional loci to the core promoter. Conclusion Our results indicate that the spasmogen specific receptor locus may be a key site of regulation determining the magnitude of spasmogen mediated ASM IPx responses during airway inflammation or following asthma medication. These data provide further insight into the

  12. B2B Pioneer A Millionaire Maker

    Institute of Scientific and Technical Information of China (English)


    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

  13. 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: [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)


    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.

  14. Diacylglycerol kinase counteracts protein kinase C-mediated inactivation of the EGF receptor

    NARCIS (Netherlands)

    Baal, van J.; Widt, de J.; Divecha, N.; Blitterswijk, van W.J.


    Epidermal growth factor receptor (EGFR) activation is negatively regulated by protein kinase C (PKC)signaling. Stimulation of A431 cells with EGF, bradykinin or UTP increased EGFR phosphorylation at Thr654 in a PKC-dependent manner. Inhibition of PKC signaling enhanced EGFR activation, as assessed b

  15. Electronic structure of MgB2

    Indian Academy of Sciences (India)

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


    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.

  16. 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


    (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......(Ca) channels contribute to NO-mediated relaxation induced by bradykinin and NS309 and, hence, may play an important role in retinal arterial endothelial function....

  17. B-2 Extremely High Frequency SATCOM and Computer Increment 1 (B-2 EHF Inc 1) (United States)


    Selected Acquisition Report (SAR) RCS: DD-A&T(Q&A)823-224 B-2 Extremely High Frequency SATCOM and Computer Increment 1 (B-2 EHF Inc 1) As of FY...10 Track to Budget 11 Cost and Funding 13 Low Rate Initial Production 19 Foreign Military Sales 20 Nuclear Costs 20 Unit Cost...Document CLIN - Contract Line Item Number CPD - Capability Production Document CY - Calendar Year DAB - Defense Acquisition Board DAE - Defense

  18. Lattice Thermal Conductivity from Atomistic Simulations: ZrB2 and HfB2 (United States)

    Lawson, John W.; Daw, Murray S.; Bauschlicher, Charles W.


    Ultra high temperature ceramics (UHTC) including ZrB2 and HfB2 have a number of properties that make them attractive for applications in extreme environments. One such property is their high thermal conductivity. Computational modeling of these materials will facilitate understanding of fundamental mechanisms, elucidate structure-property relationships, and ultimately accelerate the materials design cycle. Progress in computational modeling of UHTCs however has been limited in part due to the absence of suitable interatomic potentials. Recently, we developed Tersoff style parameterizations of such potentials for both ZrB2 and HfB2 appropriate for atomistic simulations. As an application, Green-Kubo molecular dynamics simulations were performed to evaluate the lattice thermal conductivity for single crystals of ZrB2 and HfB2. The atomic mass difference in these binary compounds leads to oscillations in the time correlation function of the heat current, in contrast to the more typical monotonic decay seen in monoatomic materials such as Silicon, for example. Results at room temperature and at elevated temperatures will be reported.

  19. Flotillins as regulators of ErbB2 levels in breast cancer

    DEFF Research Database (Denmark)

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


    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...... from 194 patients diagnosed with carcinomas of the breast showed that flotillin-2 emerged as a potential predictor of prognosis in breast cancer. Depletion of flotillin-1 and flotillin-2 leads to internalization and degradation of ErbB2. Furthermore, flotillin-1 and -2 were found to be in a molecular......-induced mechanisms. Here we show that flotillins are involved in the stabilization of ErbB2 at the plasma membrane. In SKBR3 breast cancer cells and breast cancer tissue, a positive correlation between flotillin and ErbB2 expression levels could be demonstrated. Moreover, the tissue microarray analyses of biopsies...

  20. To be or not B2B?

    CERN Document Server

    Symons, L J


    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...

  1. Transmembrane Domain Targeting Peptide Antagonizing ErbB2/Neu Inhibits Breast Tumor Growth and Metastasis

    Directory of Open Access Journals (Sweden)

    Alexia Arpel


    Full Text Available Breast cancer is still a deadly disease despite major achievements in targeted therapies designed to block ligands or ligand-binding subunits of major tyrosine kinase receptors. Relapse is significant and metastases deleterious, which demands novel strategies for fighting this disease. Here, we report a proof-of-concept experiment demonstrating that small peptides interfering with the transmembrane domain of the tyrosine kinase epidermal growth factor receptor ErbB2 exhibit anticancer properties when used at micromolar dosages in a genetically engineered mouse model of breast cancer. Different assays demonstrate the specificity of the ErbB2-targeting peptide, which induces long-term reduction of ErbB2 phosphorylation and Akt signaling consistent with reduced tumor cell proliferation and increased survival. Microcomputed tomography analysis established the antimetastatic activity of the peptide and its impact on primary tumor growth. This reveals the interior of the cell membrane as an unexplored dimension for drug design.

  2. Lotus corniculatus regulates the inflammation induced by bradykinin in a murine model of pleurisy. (United States)

    Pereira, Diana Ana; Dalmarco, Juliana Bastos; Wisniewski, Alberto; Simionatto, Edésio Luiz; Pizzolatti, Moacir Geraldo; Fröde, Tânia Silvia


    This study evaluated the anti-inflammatory efficacy of the crude extract (CE), the fractions derived from hexane (HEX), ethyl acetate (AcOEt), n-butanol (BuOH), and aqueous (Aq) and isolated compounds (oleanolic acid or kaempferitrin) obtained from the aerial parts of Lotus corniculatus var. São Gabriel in mice with bradykinin-induced pleurisy. Swiss mice were used for the In Vivo experiments. Inflammatory parameters [leukocytes; exudate concentrations; myeloperoxidase and adenosine-deaminase activities, and nitric oxide and interleukin-17 levels] were evaluated 4 h after pleurisy induction. The crude extract of Lotus corniculatus, its derived fractions, and isolated compounds inhibited leukocytes and the exudate. This inhibitory effect was associated with decreased of myeloperoxidase and adenosine-deaminase activities, nitric oxide products, and IL-17A levels. Lotus corniculatus presented important anti-inflammatory action by inhibiting leukocyte influx and exudate concentrations. This effect was directly related to the inhibition of nitric oxide and interleukinin17 levels. Oleanolic acid and kaempferitrin can account for these anti-inflammatory effects.

  3. 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


    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.

  4. 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: [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Byun, Eui-Hong, E-mail: [Department of Food Science and Technology, Kongju National University, Yesan 340-800 (Korea, Republic of)


    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

  5. The ErbB2 inhibitor Herceptin (Trastuzumab) promotes axonal outgrowth four weeks after acute nerve transection and repair. (United States)

    Placheta, Eva; Hendry, J Michael; Wood, Matthew D; Lafontaine, Christine W; Liu, Edward H; Cecilia Alvarez Veronesi, M; Frey, Manfred; Gordon, Tessa; Borschel, Gregory H


    Accumulating evidence suggests that neuregulin, a potent Schwann cell mitogen, and its receptor, ErbB2, have an important role in regulating peripheral nerve regeneration. We hypothesized that Herceptin (Trastuzumab), a monoclonal antibody that binds ErbB2, would disrupt ErbB2 signaling, allowing us to evaluate ErbB2's importance in peripheral nerve regeneration. In this study, the extent of peripheral motor and sensory nerve regeneration and distal axonal outgrowth was analyzed two and four weeks after common peroneal (CP) nerve injury in rats. Outcomes analyzed included neuron counts after retrograde labeling, histomorphometry, and protein analysis. The data analysis revealed that there was no impact of Herceptin administration on either the numbers of motor or sensory neurons that regenerated their axons but histomorphometry revealed that Herceptin significantly increased the number of regenerated axons in the distal repaired nerve after 4 weeks. Protein analysis with Western blotting revealed no difference in either expression levels of ErbB2 or the amount of activated, phosphorylated ErbB2 in injured nerves. In conclusion, administration of the ErbB2 receptor inhibitor after nerve transection and surgical repair did not alter the number of regenerating neurons but markedly increased the number of regenerated axons per neuron in the distal nerve stump. Enhanced axon outgrowth in the presence of this ErbB2 inhibitor indicates that ErbB2 signaling may limit the numbers of axons that are emitted from each regenerating neuron.


    Directory of Open Access Journals (Sweden)

    Constantin SASU


    Full Text Available Within the present paper, we propose to review some of the main aspects documented by the academic research so far with regard to the online purchasing behaviour in the B2B online environment (more specifically, in the case of the small and medium-sized companies. Preliminary conclusions reveal that, at least in the case studies, the dominant feature is that the geographic delimitation creates a potential obstacle when it comes to applying a general principle governing the small and medium-sized enterprises. Despite this, we consider that some theoretical elements can be acknowledged, elements from which future research can start to develop theories and hypothesis aimed at better explaining the phenomenon. Furthermore, the fact that the studies are rarely involving the same sector, makes it impossible to generalise the process.

  7. Producing composite materials based on ZrB2, ZrB2-SiC (United States)

    Mirovoi, Yu A.; Burlachenko, A. G.; Buyakova, S. P.; Sevostiyanova, I. N.; Kulkov, S. N.


    The effect of mechanical treatment by planetary ball milling on the properties of hot pressed ZrB2 - SiC ceramics was studied. It has been shown that material densification after mechanical treatment is finished at initial stages of sintering process. Addition of SiC causes a substantial increase in density of the sample to 99% of the theoretical powder containing 20% of silicon carbide, in comparison with samples ZrB2 density not exceeding 76%. It has been shown that all defects which were accumulated during mechanical treatment anneal in hot pressure process and there are no any changes of CDD values in sintered ceramics.

  8. Bradykinin-potentiating peptides and C-type natriuretic peptides from snake venom. (United States)

    Higuchi, S; Murayama, N; Saguchi, K; Ohi, H; Fujita, Y; Camargo, A C; Ogawa, T; Deshimaru, M; Ohno, M


    Cloning of cDNAs encoding bradykinin-potentiating peptides (BPPs)-C-type natriuretic peptide (CNP) precursor or its homologue was performed for cDNA libraries of Bothrops jararaca (South American snake), Trimeresurus flavoviridis, Trimeresurus gramineus and Agkistrodon halys blomhoffi (Asian snakes), all belonging to Crotalinae subfamily. Each cDNA library was constructed from the venom glands of a single snake to preclude ambiguity by intraspecies variation in venom components. Thirteen positive clones derived from B. jararaca were divided into two types depending on restriction sites. Differences in the nucleotide sequence arise at three locations and two of them accompanied amino acid conversions. Despite the differences, both types of cDNA clones encode the BPP-CNP precursor of 256 amino acid residues. Sequence analysis demonstrated that cDNA clones from three Asian snakes encode homologues of the BPP-CNP precursor from B. jararaca. In a precursor polypeptide, a signal sequence (approximately 25 aa) at the N-terminus is followed by sequences of BPP or the analogue (5-13 aa) with flanking spacer sequences (indefinite number of aa), an intervening linker sequence (approximately 144 aa) with unidentified function, and a CNP sequence (22 aa) with a preceding processing signal sequence (10 aa). cDNA clones from A. halys blomhoffi encode two distinct peptides in place of BPP, and T. flavoviridis and T. gramineus were shown to have considerably different sequences in the BPP domain from those known as BPP sequences. The present results provide evidence for a wide distribution of the orthologous gene expressing a series of bioactive peptides among Crotalinae subfamily.

  9. Bradykinin is degraded in hypoxic lungs and does not affect epithelial permeability

    Energy Technology Data Exchange (ETDEWEB)

    O' Brodovich, H.; Kay, J.; Coates, G.


    To investigate the effect of intravenous infusions of bradykinin (BK) on the permeability of the hypoxic pulmonary epithelium to small solutes, experiments (n = 7) were performed in yearling sheep with chronic vascular catheters. Sheep were anesthetized, intubated, paralyzed, and ventilated. After establishing stable and normal base-line pulmonary hemodynamics and blood gas tensions, the lungs were insufflated with a submicronic aerosol of technetium-/sup 99m/-labeled diethylenetriaminepentaacetate (/sup 99m/Tc-DTPA, mol wt = 492). Radioactivity arising from the right hemithorax was measured by an NaI probe with a parallel-holed collimator. The base-line pulmonary clearance rate (k) for /sup 99m/Tc-DTPA was 0.51 +/- 0.09% (SE)/min, while the sheep were ventilated with a fractional concentration of inspired O2 (FIO2) of 0.5 (arterial partial pressure of O2 (PaO2) = 196 +/- 11.4 (SE) Torr). Clearance of 99mTc-DTPA was unaffected by hypoxia alone or BK infusions in nonhypoxic lungs. The combination of an intravenous infusion of BK at either 1.2 (n = 3) or 2.4 micrograms . kg-1 . min-1 (n = 4) and alveolar hypoxia (FIO2 = 0.11, PaO2 = 28 +/- 1.6 (SE) Torr) did not affect pulmonary clearance of 99mTc-DTPA (k = 0.43 +/- 0.08% (SE)/min). In contrast, a 0.05-ml/kg intravenous infusion of oleic acid increased clearance 10-fold in one sheep. During combined hypoxia and BK infusion the pulmonary arterial BK concentration (radioimmunoassay) increased from 0.82 +/- 0.16 (SE) to 7.05 +/- 1.86 ng/ml (P less than 0.001), but the systemic arterial concentrations were unchanged (0.67 +/- 0.19 (SE) to 0.66 +/- 0.09 ng/ml).

  10. Two novel human anti-ErbB2 immunoagents are active on trastuzumab-resistant tumours (United States)

    Gelardi, T; Damiano, V; Rosa, R; Bianco, R; Cozzolino, R; Tortora, G; Laccetti, P; D'Alessio, G; De Lorenzo, C


    Background: Overexpression of ErbB2 receptor in breast cancer is associated with disease progression and poor prognosis. Trastuzumab, the only humanised anti-ErbB2 antibody currently used in breast cancer, has proven to be effective; however, a relevant problem for clinical practice is that a high fraction of breast cancer patients shows primary or acquired resistance to trastuzumab treatment. Methods: We tested on trastuzumab-resistant cells two novel human anti-tumour immunoconjugates engineered in our laboratory by fusion of a human anti-ErbB2 scFv, termed Erbicin, with either a human RNase or the Fc region of a human IgG1. Both Erbicin-derived immunoagents (EDIAs) are selectively cytotoxic for ErbB2-positive cancer cells in vitro and vivo, target an ErbB2 epitope different from that recognised by trastuzumab and do not show cardiotoxic effects. Results: We report that EDIAs are active also on trastuzumab-resistant tumour cells both in vitro and in vivo, most likely because of the different epitope recognised, as EDIAs, unlike trastuzumab, were found to be able to inhibit the signalling pathway downstream of ErbB2. Conclusion: These results suggest that EDIAs are immunoagents that could not only fulfil the therapeutic need of patients ineligible to trastuzumab treatment due to cardiac dysfunction but also prove to be useful for breast cancer patients unresponsive to trastuzumab treatment. PMID:20051960

  11. 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: [2 Department of Molecular Cellular and Animal Biology, University of Camerino, 62032 Camerino (Italy)


    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.

  12. Congenital hyperreninemic hypoaldosteronism unlinked to the aldosterone synthase (CYP11B2) gene. (United States)

    Kayes-Wandover, K M; Tannin, G M; Shulman, D; Peled, D; Jones, K L; Karaviti, L; White, P C


    Isolated hyperreninemic hypoaldosteronism presenting in infancy is usually caused by mutations in the CYP11B2 gene encoding aldosterone synthase. We studied five patients in four unrelated kindreds with hyperreninemic hypoaldosteronism, in whom we were unable to find such mutations. All presented in infancy with failure to thrive, hyponatremia, hyperkalemia, markedly elevated plasma renin activity, and low or inappropriately normal aldosterone levels. All had normal cortisol levels and no signs or symptoms of congenital adrenal hyperplasia. All responded to fludrocortisone treatment. There were no mutations detected in exons or splice junctions of CYP11B2. Linkage of the disorder to CYP11B2 was studied in two unrelated consanguineous patients and in an affected sib pair. The consanguineous patients were each heterozygous for at least one of three polymorphic microsatellite markers near CYP11B2, excluding linkage to CYP11B2. However, linkage of the disease to CYP11B2 could not be excluded in the affected sib pair. Genes involved in the regulation of aldosterone biosynthesis, including those encoding angiotensinogen, angiotensin-converting enzyme, and the AT1 angiotensin II receptor were similarly excluded from linkage. These results demonstrate the existence of an inherited form of hyperreninemic hypoaldosteronism distinct from aldosterone synthase deficiency. The affected gene(s) remain to be determined.

  13. Preferential control of basal dendritic protrusions by EphB2.

    Directory of Open Access Journals (Sweden)

    Matthew S Kayser

    Full Text Available The flow of information between neurons in many neural circuits is controlled by a highly specialized site of cell-cell contact known as a synapse. A number of molecules have been identified that are involved in central nervous system synapse development, but knowledge is limited regarding whether these cues direct organization of specific synapse types or on particular regions of individual neurons. Glutamate is the primary excitatory neurotransmitter in the brain, and the majority of glutamatergic synapses occur on mushroom-shaped protrusions called dendritic spines. Changes in the morphology of these structures are associated with long-lasting modulation of synaptic strength thought to underlie learning and memory, and can be abnormal in neuropsychiatric disease. Here, we use rat cortical slice cultures to examine how a previously-described synaptogenic molecule, the EphB2 receptor tyrosine kinase, regulates dendritic protrusion morphology in specific regions of the dendritic arbor in cortical pyramidal neurons. We find that alterations in EphB2 signaling can bidirectionally control protrusion length, and knockdown of EphB2 expression levels reduces the number of dendritic spines and filopodia. Expression of wild-type or dominant negative EphB2 reveals that EphB2 preferentially regulates dendritic protrusion structure in basal dendrites. Our findings suggest that EphB2 may act to specify synapse formation in a particular subcellular region of cortical pyramidal neurons.

  14. receptores

    Directory of Open Access Journals (Sweden)

    Salete Regina Daronco Benetti


    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”.

  15. Electronic Commerce in Tourism in China: B2B or B2C? (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.

  16. MgB2 tunnel junctions and SQUIDs

    NARCIS (Netherlands)

    Brinkman, A.; Rowell, J.M.


    Recent advances in the realization and understanding of MgB2 tunnel junctions and SQUIDs are surveyed. High quality MgB2 junctions with suitable tunnel barriers have been realized based on both oriented and epitaxial thin MgB2 films. Multiband transport properties, such as the existence of two energ

  17. 32 CFR 242b.2 - Meetings of the Board. (United States)


    ... 32 National Defense 2 2010-07-01 2010-07-01 false Meetings of the Board. 242b.2 Section 242b.2... THE HEALTH SCIENCES § 242b.2 Meetings of the Board. (a) Regular meetings. (1) The Board shall hold at... determined by the Board, meetings shall be held at the offices of the University, 4301 Jones Bridge...


    Directory of Open Access Journals (Sweden)



    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.

  19. Commensal Microbe-specific Activation of B2 Cell Subsets Contributes to Atherosclerosis Development Independently of Lipid Metabolism

    Directory of Open Access Journals (Sweden)

    Lin Chen


    Full Text Available The relation between B2 cells and commensal microbes during atherosclerosis remains largely unexplored. Here we show that under hyperlipidemic conditions intestinal microbiota resulted in recruitment and ectopic activation of B2 cells in perivascular adipose tissue, followed by an increase in circulating IgG, promoting disease development. In contrast, disruption of the intestinal microbiota by a broad-spectrum antibiotic cocktail (AVNM led to the attenuation of atherosclerosis by suppressing B2 cells, despite the persistence of serum lipid abnormalities. Furthermore, pharmacological depletion of B2 cells with an anti-B2-cell surface CD23 antibody also attenuated commensal microbe-induced atherosclerosis. Moreover, expression analysis of TLR-signaling-related genes in the activated B2 cell subsets, assessed using the Toll-Like Receptor Signaling Pathway RT2 Profiler PCR Array, confirmed activation of the B2-cell autoantibody-production axis, which was associated with an increased capacity of B2 cells to bind to intestinal microbiota. Together, our findings reveal the critical role of commensal microbe-specific activation of B2 cells in the development of atherogenesis through lipid metabolism-independent mechanisms.

  20. Galactomannan Downregulates the Inflammation Responses in Human Macrophages via NFκB2/p100

    Directory of Open Access Journals (Sweden)

    Víctor Toledano


    Full Text Available We show that galactomannan, a polysaccharide consisting of a mannose backbone with galactose side groups present on the cell wall of several fungi, induces a reprogramming of the inflammatory response in human macrophages through dectin-1 receptor. The nuclear factor kappa-light-chain-enhancer of activated B cells 2 (NFκB2/p100 was overexpressed after galactomannan challenge. Knocking down NFκB2/p100 using small interfering RNA (siRNA indicated that NFκB2/p100 expression is a crucial factor in the progression of the galactomannan-induced refractoriness. The data presented in this study could be used as a modulator of inflammatory response in clinical situations where refractory state is required.

  1. EphB–ephrin-B2 interactions are required for thymus migration during organogenesis (United States)

    Foster, Katie E.; Gordon, Julie; Cardenas, Kim; Veiga-Fernandes, Henrique; Makinen, Taija; Grigorieva, Elena; Wilkinson, David G.; Blackburn, C. Clare; Richie, Ellen; Manley, Nancy R.; Adams, Ralf H.; Kioussis, Dimitris; Coles, Mark C.


    Thymus organogenesis requires coordinated interactions of multiple cell types, including neural crest (NC) cells, to orchestrate the formation, separation, and subsequent migration of the developing thymus from the third pharyngeal pouch to the thoracic cavity. The molecular mechanisms driving these processes are unclear; however, NC-derived mesenchyme has been shown to play an important role. Here, we show that, in the absence of ephrin-B2 expression on thymic NC-derived mesenchyme, the thymus remains in the cervical area instead of migrating into the thoracic cavity. Analysis of individual NC-derived thymic mesenchymal cells shows that, in the absence of ephrin-B2, their motility is impaired as a result of defective EphB receptor signaling. This implies a NC-derived cell-specific role of EphB–ephrin-B2 interactions in the collective migration of the thymic rudiment during organogenesis. PMID:20616004

  2. Mechanical properties and microstructure of TiB2 ceramic influenced by ZrB2 additive

    Institute of Scientific and Technical Information of China (English)

    王皓; 傅正义; 辜萍; 王为民; 袁润章


    Since some transition metal diborides have the same crystal structure with TiB2, which can react with TiB2 to form solid solution by adequate technique. With ZrB2 used as additive, the TiB2-ZrB2 solid solution was prepared by hot pressing. The effects of additive content on mechanical properties of composite were investigated. The microstructure analyzing were employed by EPMA, SEM and TEM. It is shown that TiB2 can partly form solid solution with ZrB2 and redound to gain uniform grains, which h results in the increase of mechanical properties.

  3. Enhanced internalization of ErbB2 in SK-BR-3 cells with multivalent forms of an artificial ligand. (United States)

    Vaidyanath, Arun; Hashizume, Toshihiro; Nagaoka, Tadahiro; Takeyasu, Nao; Satoh, Hitomi; Chen, Ling; Wang, Jiyou; Kasai, Tomonari; Kudoh, Takayuki; Satoh, Ayano; Fu, Li; Seno, Masaharu


    Targeting and down-regulation of ErbB2, a member of EGF receptor family, is regarded as one of the key aspect for cancer treatment because it is often overexpressed in breast and ovarian cancer cells. Although natural ligands for ErbB2 have not been found, unlike other ErbB receptors, EC-1, a 20-amino acid circular peptide, has been shown to bind to ErbB2 as an artificial ligand. Previously we showed EC-1 peptide did not induce the internalization of ErbB2 in SK-BR-3 cells. In this report, we designed divalent and multivalent forms of EC-1 peptide with the Fc portion of the human IgG and bionanocapsule modified with ZZ-tag on its surface to improve the interaction with ErbB2. These forms showed higher affinity to ErbB2 than that of EC-1 monomer. Furthermore, prominent endosomal accumulation of ErbB2 occurred in SK-BR-3 cells when stimulated with EC-Fc ligand multivalently displayed on the surface of the bionanocapsule, whereas SK-BR-3 cells as themselves displayed stringent mechanism against ErbB2 internalization without stimulation. The multivalent form of EC-1 peptide appeared to internalize ErbB2 more efficiently than divalent form did. This internalization was unaffected by the inhibition of clathrin association, but inhibited when the cholesterol was depleted which explained either caveolar or GPI-AP-early endocytic compartment (GEEC) pathway. Because of the lack of caveolin-1 expression, caveolar machinery may be lost in SK-BR-3 cell line. Therefore, it is suggested that the multivalent form of EC-1 induces the internalization of ErbB2 through the GEEC pathway.

  4. Transgenic expression of an altered angiotensin type I AT1 receptor resulting in marked modulation of vascular type I collagen. (United States)

    Yu, Jun; Taylor, Linda; Rich, Celeste; Toselli, Paul; Stone, Philip; Green, Daniel; Warburton, Rod; Hill, Nicholas; Goldstein, Ronald; Polgar, Peter


    The angiotensin II (AngII) type I receptor (AT1) was modified by replacing its third intracellular loop and C-terminal tail with the corresponding regions from the bradykinin B2 receptor. Transgenic mice were produced that overexpress this mutated receptor (AB3T). Considerably less collagen content in the intact aorta and in primary aortic smooth muscle cells (aSMCs) cultures was observed in the transgenic mice. On the other hand, elastin content remained unchanged as measured by Western blot, and insoluble amino acid quantitation. The contraction of isolated aortas also remained unaltered. The aSMCs derived from the transgenic mice showed a reduction in AngII responsive type I collagen production. In aSMCs from transgenic mice, the cascade of Akt to the mammalian target rapamycin (mTOR) to p70 S6 kinase (p70S6K) was not AngII activated, while in the aSMCs from wild-type (WT) mice the cascade was AngII activated. Angiotensin activation of Smad2 and Stat3 was also reduced in the AB3T aSMCs. However, no change in the effect of transforming growth factor β (TGFβ) on type I collagen production was observed. Also, the activation of ERK and JNK and G-protein linked signaling remained unaltered in response to AngII. Akt and PI3K activation inhibitors blocked AngII-stimulated type I collagen expression in WT aSMCs, whereas ERK inhibitor had no such effect. Our results point to an Akt/mTOR/p70S6K regulation of collagen production by AngII with participation of Smad2 and Stat3 cascades in this process.

  5. Electrophysiological responses to bradykinin and microinjected inositol polyphosphates in neuroblastoma cells : Possible role of inositol 1,3,4-trisphosphate in altering membrane potential

    NARCIS (Netherlands)

    Tertoolen, L.G.J.; Tilly, B.C.; Irvine, R.F.; Molenaar, W.H.


    Addition of bradykinin to mouse N1E-115 neuroblastoma cells evokes a rapid but transient rise in cytoplasmic free Ca2+ concentration ([Ca2+]i). The [Ca2+]i rise is accompanied by a transient membrane hyperpolarization, due to a several-fold increase in K+ conductance, followed by a prolonged depolar

  6. ErbB2-dependent chemotaxis requires microtubule capture and stabilization coordinated by distinct signaling pathways.

    Directory of Open Access Journals (Sweden)

    Khedidja Benseddik

    Full Text Available Activation of the ErbB2 receptor tyrosine kinase stimulates breast cancer cell migration. Cell migration is a complex process that requires the synchronized reorganization of numerous subcellular structures including cell-to-matrix adhesions, the actin cytoskeleton and microtubules. How the multiple signaling pathways triggered by ErbB2 coordinate, in time and space, the various processes involved in cell motility, is poorly defined. We investigated the mechanism whereby ErbB2 controls microtubules and chemotaxis. We report that activation of ErbB2 increased both cell velocity and directed migration. Impairment of the Cdc42 and RhoA GTPases, but not of Rac1, prevented the chemotactic response. RhoA is a key component of the Memo/ACF7 pathway whereby ErbB2 controls microtubule capture at the leading edge. Upon Memo or ACF7 depletion, microtubules failed to reach the leading edge and cells lost their ability to follow the chemotactic gradient. Constitutive ACF7 targeting to the membrane in Memo-depleted cells reestablished directed migration. ErbB2-mediated activation of phospholipase C gamma (PLCγ also contributed to cell guidance. We further showed that PLCγ signaling, via classical protein kinases C, and Memo signaling converged towards a single pathway controlling the microtubule capture complex. Finally, inhibiting the PI3K/Akt pathway did not affect microtubule capture, but disturbed microtubule stability, which also resulted in defective chemotaxis. PI3K/Akt-dependent stabilization of microtubules involved repression of GSK3 activity on the one hand and inhibition of the microtubule destabilizing protein, Stathmin, on the other hand. Thus, ErbB2 triggers distinct and complementary pathways that tightly coordinate microtubule capture and microtubule stability to control chemotaxis.

  7. Substitution of Mn for Mg in MgB_2* (United States)

    Fitzpatrick, Michael D.; Johnston, David C.; Miller, Lance L.; Hill, Julienne M.


    The study of solid solutions in which the Mg in MgB2 is partially replaced by magnetic 3d or 4f atoms can potentially reveal important information on the superconducting state of MgB_2. As an end-member of the hypothetical Mg_1-xMn_xB2 system, MnB2 is isostructural with MgB2 and is an antiferromagnet below TN = 760 K which becomes canted at 157 K. A previous study by Moritomo et al.[1] examined the structure and properties of multi-phase samples with 0.01J. Phys. Soc. Japan b70, 1889 (2001).; “Effects of transition metal doping in MgB2 superconductor", Y. Moritomo at al. arXiv:cond-mat/0104568.

  8. 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


    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.

  9. Harnessing marketing automation for B2B content marketing


    Järvinen, Joel; Taiminen, Heini


    The growing importance of the Internet to B2B customer purchasing decisions has motivated B2B sellers to create digital content that leads potential buyers to interact with their company. This trend has engendered a new paradigm referred to as ‘content marketing.’ This study investigates the organizational processes for developing valuable and timely content to meet customer needs and for integrating content marketing with B2B selling processes. The results of this single case study demonstra...

  10. Boron isotope effect in superconducting MgB2. (United States)

    Bud'ko, S L; Lapertot, G; Petrovic, C; Cunningham, C E; Anderson, N; Canfield, P C


    We report the preparation method of and boron isotope effect for MgB2, a new binary intermetallic superconductor with a remarkably high superconducting transition temperature T(c)(10B) = 40.2 K. Measurements of both temperature dependent magnetization and specific heat reveal a 1.0 K shift in T(c) between Mg11B2 and Mg10B2. Whereas such a high transition temperature might imply exotic coupling mechanisms, the boron isotope effect in MgB2 is consistent with the material being a phonon-mediated BCS superconductor.



    Slanič, Matej


    V diplomski nalogi opredelimo vlogo B2B portalov in pomen elektronskega poslovanja. B2B portale smo razvrstili glede na različne kriterije in predstavili različne modele trgovanja na njih. Velik del pozornosti smo posvetili tudi strateškemu načrtovanju B2B poslovanja in vključevanju podjetij na B2B portale, dotaknili pa smo se tudi vizije elektronskega poslovanja. Osrednji del naloge obsega predstavitev gradnje specifičnega portala ter z njo povezane oblikovne in tehnološke rešitv...

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


    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.

  13. Multiband model for tunneling in MgB2 junctions

    NARCIS (Netherlands)

    Brinkman, A.; Golubov, A.A.; Rogalla, H.; Dolgov, O.V.; Kortus, J.; Kong, Y.; Jepsen, O.; Andersen, O.K.


    A theoretical model for quasiparticle and Josephson tunneling in multiband superconductors is developed and applied to MgB2-based junctions. The gap functions in different bands in MgB2 are obtained from an extended Eliashberg formalism, using the results of band structure calculations. The temperat

  14. Plexin-B2 negatively regulates macrophage motility, Rac, and Cdc42 activation.

    Directory of Open Access Journals (Sweden)

    Kelly E Roney

    Full Text Available Plexins are cell surface receptors widely studied in the nervous system, where they mediate migration and morphogenesis though the Rho family of small GTPases. More recently, plexins have been implicated in immune processes including cell-cell interaction, immune activation, migration, and cytokine production. Plexin-B2 facilitates ligand induced cell guidance and migration in the nervous system, and induces cytoskeletal changes in overexpression assays through RhoGTPase. The function of Plexin-B2 in the immune system is unknown. This report shows that Plexin-B2 is highly expressed on cells of the innate immune system in the mouse, including macrophages, conventional dendritic cells, and plasmacytoid dendritic cells. However, Plexin-B2 does not appear to regulate the production of proinflammatory cytokines, phagocytosis of a variety of targets, or directional migration towards chemoattractants or extracellular matrix in mouse macrophages. Instead, Plxnb2(-/- macrophages have greater cellular motility than wild type in the unstimulated state that is accompanied by more active, GTP-bound Rac and Cdc42. Additionally, Plxnb2(-/- macrophages demonstrate faster in vitro wound closure activity. Studies have shown that a closely related family member, Plexin-B1, binds to active Rac and sequesters it from downstream signaling. The interaction of Plexin-B2 with Rac has only been previously confirmed in yeast and bacterial overexpression assays. The data presented here show that Plexin-B2 functions in mouse macrophages as a negative regulator of the GTPases Rac and Cdc42 and as a negative regulator of basal cell motility and wound healing.

  15. B2B myynnin johtaminen ravintola-alalla


    Pajari, Katja


    Tämän opinnäytetyön tavoitteena oli selvittää, miten ravintola-alan yrityksissä johdetaan B2B myyntiä. Tarkoituksena oli kartoittaa, miten yrityksissä panostetaan B2B myyntiin ja sen johtamiseen sekä millä tavoin yritysmyyntiä johdetaan. Tutkimus pohjautuu opinnäytetyön tietoperustaan, jossa käsitellään B2B myyntiprosessia ja myynnin johtamista. Työssä käsitellään B2B myyntiä ja selvitetään myyntiprosessin eri vaiheita. Aihe on rajattu koskemaan nimenomaan johtamisen näkökulmaa B2B myynni...

  16. Pulse Plating of Copper-ZrB2 Composite Coatings

    Institute of Scientific and Technical Information of China (English)

    Dongming GUO; Min ZHANG; Zhuji JIN; Renke KANG


    Copper-zirconium diboride (ZrB2) composite coatings were fabricated using pulse plating technique to acquire a new type of EDM (electro-discharge machining) electrode material. The effects of pulse parameters, i.e., the average current density, the frequency and the duty cycle, on the incorporation of ZrB2 particles in the copper matrix were investigated. The amountof codeposited ZrB2 particles had a maximum at average current density of 3 A/dm2 and increased with decreasing duty cycle as well as current frequency of the pulse current used for deposition. The hardness of the coatings increased with increasing ZrB2 percentage, whereas the incorporation of ZrB2 particles had little effect on the resistivity of the composites.

  17. 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


    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...

  18. Novel Roles for Kv7 Channels in Shaping Histamine-Induced Contractions and Bradykinin-Dependent Relaxations in Pig Coronary Arteries. (United States)

    Chen, Xingjuan; Li, Wennan; Hiett, S Christopher; Obukhov, Alexander G


    Voltage-gated Kv7 channels are inhibited by agonists of Gq-protein-coupled receptors, such as histamine. Recent works have provided evidence that inhibition of vascular Kv7 channels may trigger vessel contractions. In this study, we investigated how Kv7 activity modulates the histamine-induced contractions in "healthy" and metabolic syndrome (MetS) pig right coronary arteries (CAs). We performed isometric tension and immunohistochemical studies with domestic, lean Ossabaw, and MetS Ossabaw pig CAs. We found that neither the Kv7.2/Kv7.4/Kv7.5 activator ML213 nor the general Kv7 inhibitor XE991 altered the tension of CA rings under preload, indicating that vascular Kv7 channels are likely inactive in the preloaded rings. Conversely, ML213 potently dilated histamine-pre-contracted CAs, suggesting that Kv7 channels are activated during histamine applications and yet partially inhibited by histamine. Immunohistochemistry analysis revealed strong Kv7.4 immunostaining in the medial and intimal layers of the CA wall, whereas Kv7.5 immunostaining intensity was strong in the intimal but weak in the medial layers. The medial Kv7 immunostaining was significantly weaker in MetS Ossabaw CAs as compared to lean Ossabaw or domestic CAs. Consistently, histamine-pre-contracted MetS Ossabaw CAs exhibited attenuated ML213-dependent dilations. In domestic pig CAs, where medial Kv7 immunostaining intensity was stronger, histamine-induced contractions spontaneously decayed to ~31% of the peak amplitude within 4 minutes. Oppositely, in Ossabaw CAs, where Kv7 immunostaining intensity was weaker, the histamine-induced contractions were more sustained. XE991 pretreatment significantly slowed the decay rate of histamine-induced contractions in domestic CAs, supporting the hypothesis that increased Kv7 activity correlates with a faster rate of histamine-induced contraction decay. Alternatively, XE991 significantly decreased the amplitude of bradykinin-dependent dilations in pre-contracted CAs

  19. Preparation of MgB2 Superconducting Materials%MgB2超导材料的制备

    Institute of Scientific and Technical Information of China (English)




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

    DEFF Research Database (Denmark)

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


    High-pressure X-ray diffraction in ScB2, TiB2, YB4 and HoB4 powders and single crystals has been studied using synchrotron radiation as well as conventional X-rays. The experimental results are supported by calculations using density functional theory. ScB2, YB4 and HoB4 are hard materials (bulk...... 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...

  1. Fine-Filament MgB2 Superconductor Wire (United States)

    Cantu, Sherrie


    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 (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.

  2. 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


    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.

  3. B2B virksomheders brug af sociale medier


    Persdatter Gotfredsen, Karoline


    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...

  4. B2B营销的权威

    Institute of Scientific and Technical Information of China (English)



    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。

  5. A systematic expression analysis implicates Plexin-B2 and its ligand Sema4C in the regulation of the vascular and endocrine system. (United States)

    Zielonka, Matthias; Xia, Jingjing; Friedel, Roland H; Offermanns, Stefan; Worzfeld, Thomas


    Plexins serve as receptors for semaphorins and play important roles in the developing nervous system. Plexin-B2 controls decisive developmental programs in the neural tube and cerebellum. However, whether Plexin-B2 also regulates biological functions in adult nonneuronal tissues is unknown. Here we show by two methodologically independent approaches that Plexin-B2 is expressed in discrete cell types of several nonneuronal tissues in the adult mouse. In the vasculature, Plexin-B2 is selectively expressed in functionally specialized endothelial cells. In endocrine organs, Plexin-B2 localizes to the pancreatic islets of Langerhans and to both cortex and medulla of the adrenal gland. Plexin-B2 expression is also detected in certain types of immune and epithelial cells. In addition, we report on a systematic comparison of the expression patterns of Plexin-B2 and its ligand Sema4C, which show complementarity or overlap in some but not all tissues. Furthermore, we demonstrate that Plexin-B2 and its family member Plexin-B1 display largely nonredundant expression patterns. This work establishes Plexin-B2 and Sema4C as potential regulators of the vascular and endocrine system and provides an anatomical basis to understand the biological functions of this ligand-receptor pair.

  6. Bending strain tolerance of MgB2 superconducting wires (United States)

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


    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.

  7. 26 CFR 301.7701(b)-2 - Closer connection exception. (United States)


    ...) PROCEDURE AND ADMINISTRATION PROCEDURE AND ADMINISTRATION Definitions § 301.7701(b)-2 Closer connection...) Tax home—(1) Definition. For purposes of section 7701 (b) and the regulations under that section,...

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

    Directory of Open Access Journals (Sweden)

    Wai Wai Lin


    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.

  9. 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


    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.

  10. Attempts at doping indium in MgB2

    DEFF Research Database (Denmark)

    Grivel, Jean-Claude


    Indium (In) doped MgB2 polycrystalline samples were prepared by solid-liquid phase reaction in Ar. After reaction at 800 °C, less than 1 at.% Mg was replaced by In in the MgB2 phase, without significant influence on its lattice parameters and only a slight decrease of its superconducting transition...... in both the doped and undoped samples....

  11. Branding of electricity in B2B markets


    Rolanda Simenaite 1986


    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 ...

  12. CIAE Signs Contract on B1/B2 Project

    Institute of Scientific and Technical Information of China (English)


    CIAE signed Contract on Design,Commissioning and Technology Service for B1/B2 Project of Birine Reactor with CZEC in December,2015.The B1/B2 project which was won over by CZEC is PhaseⅠand PhaseⅡof an Algeria project which aimed to upgrade and rebuild Algeria Birine Nuclear Research Center.According to the contract with total fund amounting to 110million Yuan,CIAE will provide

  13. Phonon dispersion and electron-phonon coupling in MgB2 and AlB2. (United States)

    Bohnen, K P; Heid, R; Renker, B


    We present a first principles investigation of the lattice dynamics and electron-phonon coupling of the superconductor MgB2 and the isostructural AlB2 within the framework of density functional perturbation theory using a mixed-basis pseudopotential method. Complete phonon dispersion curves and Eliashberg functions alpha2F are calculated for both systems. The main differences are related to high frequency in-plane boron vibrations, which are strongly softened in MgB2 and exhibit an exceptionally strong electron-phonon coupling. We also report on Raman measurements, which support the theoretical findings. Implications for the superconducting transition temperature are briefly discussed.

  14. Superconductivity in dense MgB2 wires. (United States)

    Canfield, P C; Finnemore, D K; Bud'ko, S L; Ostenson, J E; Lapertot, G; Cunningham, C E; Petrovic, C


    MgB2 becomes superconducting just below 40 K. 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 microm, are better than 80% dense, and manifest the full chi = -1/4pi shielding in the superconducting state. Temperature-dependent resistivity measurements indicate that MgB2 is a highly conducting metal in the normal state with rho(40 K) = 0.38 microOmega cm. By using this value, an electronic mean-free path, l approximately 600 A 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.

  15. Mechanical and thermal properties of bulk ZrB2 (United States)

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


    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.

  16. c-erbB-2 expression and nuclear pleomorphism in canine mammary tumors

    Directory of Open Access Journals (Sweden)

    Dutra A.P.


    Full Text Available The objective of the present investigation was to study the expression of c-erbB-2 and MIB-1 and try to associate them with morphological features of the cell such as nuclear pleomorphism, mitotic count and histological grade in a series of 70 canine mammary gland tumors, 22 of them benign and 48 malignant. Tumors were collected at the Veterinary Hospital of UFMG (Brazil and the Veterinary Faculty of Porto University (Portugal. c-erbB-2 expression was determined according to the guidelines provided by the manufacturer of the HercepTest system and nuclear pleomorphism, mitotic count and histological grade according the Elston and Ellis grading system. The HercepTest is the FDA-approved in vitro diagnostic test marketed by Dako. It is a semi-quantitative immunohistochemical assay used to determine overexpression of HER2 protein (human epidermal growth factor receptor in breast cancer tissue. MIB-1 expression was also evaluated in 28 malignant tumors. Seventeen (35.4% of the malignant tumors were positive for c-erbB-2 expression, which was positively associated with nuclear pleomorphism (P < 0.0001, histological grade (P = 0.0017 and mitotic count (P < 0.05. Nuclear pleomorphism also showed a positive association with MIB-1 index (P < 0.0001. These results suggest that some of the biological and morphological characteristics of the tumor are associated in canine mammary gland tumors, as also reported for human breast cancer. It was also possible to show that the immunoexpression of c-erbB-2 can be a factor in mammary carcinogenesis. This fact opens the possibility of using anti-c-erbB-2 antibodies in the treatment of canine mammary tumors.

  17. Correlation of expression of ER,PR and c-erbB-2 with ultrasonographic features in invasive ductal cancer of breast

    Institute of Scientific and Technical Information of China (English)


    Objective To analyze the relationship of the expression level of estrogen receptor(ER),progesterone receptor(PR)and human epidermal growth factor receptor-2(HER-2,c-erbB-2)of breast invasive ductal carcinoma(IDC)with ultrasonographic characteristics.Methods Totally 104 patients with IDCs confirmed pathologically were involved in this study.ER,PR and c-erbB-2 expression in the IDC specimens was determined by immunohistochemical staining technique.The correlation between the ultrasonographic features and the ...

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

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Yuan, E-mail:; Cardell, Lars-Olaf


    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

  19. B-B bond activation and NHC ring-expansion reactions of diboron(4) compounds, and accurate molecular structures of B2(NMe2)4, B2eg2, B2neop2 and B2pin2. (United States)

    Eck, Martin; Würtemberger-Pietsch, Sabrina; Eichhorn, Antonius; Berthel, Johannes H J; Bertermann, Rüdiger; Paul, Ursula S D; Schneider, Heidi; Friedrich, Alexandra; Kleeberg, Christian; Radius, Udo; Marder, Todd B


    In this detailed study we report on the structures of the widely employed diboron(4) compounds bis(pinacolato)diboron (B2pin2) and bis(neopentyl glycolato)diboron (B2neop2), as well as bis(ethylene glycolato)diboron (B2eg2) and tetrakis(dimethylamino)diboron (B2(NMe2)4), and their reactivity, along with that of bis(catecholato)diboron (B2cat2) with backbone saturated and backbone unsaturared N-heterocyclic carbenes (NHCs) of different steric demand. Depending on the nature of the diboron(4) compound and the NHC used, Lewis-acid/Lewis-base adducts or NHC ring-expansion products stemming from B-B and C-N bond activation have been observed. The corresponding NHC adducts and NHC ring-expanded products were isolated and characterised via solid-state and solution NMR spectroscopy and X-ray diffraction. In general, we observed B-B bond and C-N bond activation at low temperature for B2eg2, at room temperature for B2neop2 and at higher temperature for B2cat2. The reactivity strongly depends on steric effects of the NHCs and the diboron(4) compounds, as well as on the corresponding Lewis-basicity and Lewis-acidity. Our results provide profound insight into the chemistry of these diboron(4) reagents with the nowadays ubiquitous NHCs, the stability of the corresponding NHC adducts and on B-B bond activation using Lewis-bases in general. We demonstrate that B-B bond activation may be triggered even at temperatures as low as -40 °C to -30 °C without any metal species involved. For example, the reactions of B2eg2 with sterically less demanding NHCs such as Me2Im(Me) and iPr2Im in solution led to the corresponding ring-expanded products at low temperatures. Furthermore, boronium [L2B(OR)2](+) and borenium [LB(OR)2](+) cations have been observed from the reaction of the bis-borate B2eg3 with the NHCs iPr2Im and Me2Im(Me), which led to the conclusion that the activation of bis-borates with NHCs (or Lewis-bases in general) might be a facile and simple route to access such species.

  20. Mechanisms of Trastuzumab resistance in ErbB2-driven breast cancer and newer opportunities to overcome therapy resistance

    Directory of Open Access Journals (Sweden)

    Tameka A Bailey


    Full Text Available The Human Epidermal Growth Factor Receptor 2 (Her2, ErbB2 or Neu is overexpressed in about 20 - 25% of breast cancers and is causally linked to oncogenesis, providing opportunities for targeted therapy. Trastuzumab (Herceptin™, Genentech Inc, San Francisco, CA, a humanized monoclonal antibody against ErbB2, is a successful example of this concept and has vastly improved the response to treatment and overall survival in a majority of ErbB2+ breast cancer patients. However, lack of response in some patients as well as relapse during the course of therapy in others, continue to challenge researchers and clinicians alike towards a better understanding of the fundamental mechanisms of Trastuzumab action and resistance to treatment. The exact in vivo mechanism of action of Trastuzumab remains enigmatic, given its direct effects on the ErbB2 signaling pathway as well as indirect contributions from the immune system, by virtue of the ability of Trastuzumab to elicit Antibody-Dependent Cellular Cytotoxicity. Consequently, multiple mechanisms of resistance have been proposed. We present here a comprehensive review of our current understanding of the mechanisms, both of Trastuzumab action and clinical resistance to Trastuzumab-based therapies. We also review newer strategies (based on ErbB2 receptor biology that are being explored to overcome resistance to Trastuzumab therapy.

  1. The deaf and the dumb: the biology of ErbB-2 and ErbB-3. (United States)

    Citri, Ami; Skaria, Kochupurakkal Bose; Yarden, Yosef


    ErbB-2 (also called HER2/neu) and ErbB-3 are closely related to the epidermal growth factor receptor (EGFR/ErbB-1), but unlike EGFR, ErbB-2 is a ligandless receptor, whereas ErbB-3 lacks tyrosine kinase activity. Hence, both ErbB-2 and ErbB-3 are active only in the context of ErbB heterodimers, and ErbB-2. ErbB-3 heterodimers, which are driven by neuregulin ligands, are the most prevalent and potent complexes. These stringently controlled heterodimers are repeatedly employed throughout embryonic development and dictate the establishment of several cell lineages through mesenchyme-epithelial inductive processes and the interactions of neurons with muscle, glia, and Schwann cells. Likewise, the potent combination of signaling pathways engaged by the heterodimers drives an aggressive phenotype of tumors of secretory epithelia, including breast and lung cancers. This review highlights recent structural insights into the mechanism of ligand-induced heterodimer formation, and concentrates on signaling pathways employed by ErbB-2 and ErbB-3 in normal and in malignant cells.

  2. Mechanical Spectroscopy of MgB2 Containing Sic / Spektroskopia Mechaniczna MgB2 Zawierającego Sic

    Directory of Open Access Journals (Sweden)

    Silva M.R.


    Full Text Available The compound magnesium diboride (MgB2 has been well-known since the 1950s; however, its superconducting properties were unknown. Intrinsic characteristics of MgB2 make this material a promising candidate for technological applications, although the low value of the irreversibility field and the decrease in critical current density with the increase in the magnetic field considerably reduce its utility. The present work aimed to study the effect of carbon-based doping on anelastic properties of MgB2 as measured by mechanical spectroscopy. The samples were prepared by using the powder-intube method. The samples were made with 5, 7.5, and 10 wt.% of silicon carbide (SiC. The results reveal complex mechanical loss spectra caused by the interaction between point defects and surface defects in the crystalline lattice of MgB2.

  3. Possible antiferromagnetic interactions in NdRh 3B 2 and CeRh 3B 2 (United States)

    Takeda, K.; Kohara, T.; Kitaoka, Y.; Asayama, K.


    The magnetic phase transition and spin arrangement in the ordered phase of NdRh3B2 and CeRh3B2 have been studied by measurements of magnetic susceptibility and heat capacity of the isostructural compounds RRh3B2 ( R: La, Ce, Nd, Gd). The existence of small antiferromagnetic interactions between R ions ( R = Nd, Ce) on the neighbouring ferromagnetic chains along the c-axis has been suggested. This model gives another aspect to explain the origin of the anomalous magnetism of CeRh3B2 such as the small value of magnetic moment in the ordered state and the curious behaviour of susceptibility. The magnitude of the effective moment of Ce has been estimated for the consumption of magnetic entropy of the Ce compound.

  4. Lattice Thermal Conductivity of Ultra High Temperature Ceramics ZrB2 and HfB2 from Atomistic Simulations (United States)

    Lawson, John W.; Murray, Daw S.; Bauschlicher, Charles W., Jr.


    Atomistic Green-Kubo simulations are performed to evaluate the lattice thermal conductivity for single crystals of the ultra high temperature ceramics ZrB2 and HfB2 for a range of temperatures. Recently developed interatomic potentials are used for these simulations. Heat current correlation functions show rapid oscillations which can be identified with mixed metal-Boron optical phonon modes. Agreement with available experimental data is good.

  5. 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


    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.

  6. Deregulated ephrin-B2 expression in the mammary gland interferes with the development of both the glandular epithelium and vasculature and promotes metastasis formation. (United States)

    Haldimann, Mirjam; Custer, Domenica; Munarini, Nadia; Stirnimann, Christoph; Zürcher, Gisela; Rohrbach, Valeria; Djonov, Valentin; Ziemiecki, Andrew; Andres, Anne-Catherine


    Eph receptor tyrosine kinases and their membrane-bound ephrin ligands play key roles during morphogenesis and adult tissue homeostasis. Receptor-ligand interactions result in forward and reverse signalling from the receptor and ligand respectively. To delineate the role(s) of forward and reverse signalling in mammary gland biology we have established transgenic mice exhibiting mammary epithelial-specific overexpression of either the native ephrin-B2 or a dominant negative ephrin-B2 mutant incapable of reverse signalling. During pregnancy and lactation overexpression of the native ephrin-B2 resulted in precocious differentiation, whereas overexpression of mutated ephrin-B2 caused delayed epithelial differentiation and in disturbed tissue architecture. Both transgenes affected also mammary vascularisation. Whereas ephrin-B2 induced superfluous but organised capillaries, mutant ephrin-B2 overexpression resulted in an irregular vasculature with blind-ending capillaries. Mammary tumours were not observed in either transgenic line, however, the crossing with NeuT transgenic animals revealed that mutated ephrin-B2 expression significantly accelerated tumour growth and imposed a metastatic phenotype.

  7. 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


    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.

  8. Bradykinin modulates potassium and calcium currents in neuroblastoma hybrid cells via different pertussis toxin-insensitive pathways. (United States)

    Wilk-Blaszczak, M A; Gutowski, S; Sternweis, P C; Belardetti, F


    In NG108-15 cells, bradykinin (BK) activates a potassium current (IK,BK) and inhibits the voltage-dependent calcium current (ICa,V). BK also stimulates a phosphatidylinositol-specific phospholipase C (PI-PLC). The subsequent release of inositol 1,4,5-trisphosphate and increase in intracellular calcium contribute to IK,BK, through activation of a calcium-dependent potassium current. In membranes from these cells, stimulation of PI-PLC by BK is mediated by Gq and/or G11, two homologous, pertussis toxin-insensitive G proteins. Here, we have investigated the role of Gq/11 in the electrical responses to BK. GTP gamma S mimicked and occluded both actions of BK, and both effects were insensitive to pertussis toxin. Perfusion of an anti-Gq/11 alpha antibody into the pipette suppressed IK,BK, but not the inhibition of ICa,V by BK. Thus, BK couples to IK,BK via Gq/11, but coupling to ICa,V is most likely via a different, pertussis toxin-insensitive G protein.

  9. Altered cardiac bradykinin metabolism in experimental diabetes caused by the variations of angiotensin-converting enzyme and other peptidases. (United States)

    Adam, Albert; Leclair, Patrick; Montpas, Nicolas; Koumbadinga, Gérémy Abdull; Bachelard, Hélène; Marceau, François


    The peptidases angiotensin-converting enzyme (ACE) and neutral endopeptidase 24.11 (NEP) mediate most of the kinin catabolism in normal cardiac tissue and are the molecular targets of inhibitory drugs that favorably influence diabetic complications. We studied the variations of those kininases in the myocardium of rats in experimental diabetes. ACE and NEP activities were significantly decreased in heart membranes 4-8weeks post-streptozotocin (STZ) injection. However, insulin-dependent diabetes did not modify significantly bradykinin (BK) half-life (t(1/2)) while the effect of both ACE (enalaprilat) and ACE and NEP (omapatrilat) inhibitors on BK degradation progressively decreased, which may be explained by the upregulation of other unidentified metallopeptidase(s). In vivo insulin treatment restored the activities of both ACE and NEP. ACE and NEP activities were significantly higher in hearts of young Zucker rats than in those of Sprague-Dawley rats. BK t(1/2) and the effects of peptidase inhibitors on t(1/2) varied accordingly. It is concluded that kininase activities are subjected to large and opposite variations in rat cardiac tissue in type I and II diabetes models. A number of tissue or molecular factors may determine these variations, such as remodeling of cardiac tissue, ectoenzyme shedding to the extracellular fluid and the pathologic regulation of peptidase gene expression.

  10. EBSD analysis of MgB2 bulk superconductors (United States)

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


    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.

  11. MgB2 superconducting wires basics and applications

    CERN Document Server


    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.

  12. 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......, service, configuration and customisation of the products in their company as well as to develop an apposite understanding of the key values and characteristics of the client organisation. Based on a design-ethnographical study of real sales practice in lift truck business the paper draws parallels between...

  13. Superconducting properties of MgB2 from first principles. (United States)

    Floris, A; Profeta, G; Lathiotakis, N N; Lüders, M; Marques, M A L; Franchini, C; Gross, E K U; Continenza, A; Massidda, S


    Solid MgB(2) has rather interesting and technologically important properties, such as a very high superconducting transition temperature. Focusing on this compound, we report the first nontrivial application of a novel density-functional-type theory for superconductors, recently proposed by the authors. Without invoking any adjustable parameters, we obtain the transition temperature, the gaps, and the specific heat of MgB(2) in very good agreement with experiment. Moreover, our calculations show how the Coulomb interaction acts differently on sigma and pi states, thereby stabilizing the observed superconducting phase.

  14. Superconductivity of metallic boron in MgB2. (United States)

    Kortus, J; Mazin, I I; Belashchenko, K D; Antropov, V P; Boyer, L L


    Boron in MgB2 forms stacks of honeycomb layers with magnesium as a space filler. Band structure calculations indicate that Mg is substantially ionized, and the bands at the Fermi level derive mainly from B orbitals. Strong bonding with an ionic component and considerable metallic density of states yield a sizable electron-phonon coupling. Together with high phonon frequencies, which we estimate via zone-center frozen phonon calculations to be between 300 and 700 cm(-1), this produces a high critical temperature, consistent with recent experiments. Thus MgB2 can be viewed as an analog of the long sought, but still hypothetical, superconducting metallic hydrogen.

  15. Is Lithium Sulfide a MgB2-like Superconductor?


    Isikaku-Ironkwe, O. P.


    Lithium Sulfide, Li2S, is an anti-fluorite semiconductor with a band-gap of 3.865 eV. It also has exactly the same valence electron count, Ne, and atomic number, Z, as magnesium diboride, MgB2. Both have almost the same formula weight. This qualifies Li2S as a magnesium-diboride like material. Li2S passes the same computational material specific test for superconductivity as MgB2. Using our recently developed symmetry rules for searching for superconductors, we predict that Li2S, with electro...

  16. 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


    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.

  17. Isostructural Transition of MgB2 Under High Pressure

    Institute of Scientific and Technical Information of China (English)

    SUN Li-Ling; WU Qi; ZHAN Zai-Ji; WANG Wen-Kui; WANG Wen-Kui; T.Kikegawa


    The high-pressure behaviour of the superconductor MgB2 with a hexagonal structure has been investigated by the in situ synchrotron radiation x-ray diffraction method under pressures up to 42.2 GPa in a diamond anvil cell. An abrupt decrease of about 7% in the unit cell volume of this material occurs in the pressure range of 26.3-30.2 GPa. A split of the Raman spectrum was also observed. The jump of the compression curve and Raman spectrum are ascribed to an isostructural transition in MgB2 at a pressure of 30.2 GPa.

  18. Customized E-Learning for B2B Companies

    Directory of Open Access Journals (Sweden)

    Tim Thomasma


    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.

  19. 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"


    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 ...

  20. Multiband model for penetration depth in MgB2

    NARCIS (Netherlands)

    Golubov, A.A.; Brinkman, A.; Dolgov, O.V.; Kortus, J.; Jepsen, O.


    The results of first-principles calculations of the electronic structure and the electron-phonon interaction in MgB2 are used to study theoretically the temperature dependence and anisotropy of the magnetic-field penetration depth. The effects of impurity scattering are essential for a proper descri

  1. Itinerant magnetism in CeRh3B2

    DEFF Research Database (Denmark)

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


    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...

  2. Investigation of TaC–TaB2 ceramic composites

    Indian Academy of Sciences (India)

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


    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.

  3. 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


    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.

  4. Supporting B2B Business Documents in XML Web Services

    Institute of Scientific and Technical Information of China (English)

    KIM Hyoungdo


    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.

  5. Marketing-sales interface configurations in B2B firms

    NARCIS (Netherlands)

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


    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

  6. Superconductivity in MgB2: Clean or Dirty?

    NARCIS (Netherlands)

    Mazin, I.I.; Andersen, O.K.; Jepsen, O.; Dolgov, O.V.; Kortus, J.; Golubov, A.A.; Kuz'menko, A.B.; Marel, van der D.


    A large number of experimental facts and theoretical arguments favor a two-gap model for superconductivity in MgB2. However, this model predicts strong suppression of the critical temperature by interband impurity scattering and, presumably, a strong correlation between the critical temperature and

  7. Oxidation of ZrB2 and ZrB2-SiC Ceramics With Tungsten Additions (Preprint) (United States)


    Electrochemical Society . PAO Case Number: 88 ABW-2008-1143; Clearance Date: 26 Nov 2008. Paper contains color. 14. ABSTRACT The effect of tungsten...18 For submission to proceedings of the 214th meeting of the Electrochemical Society Oxidation of ZrB2 and ZrB2-SiC Ceramics with Tungsten...TaSi2 that form a protective SiO2-rich oxide scale at temperatures 1 For submission to proceedings of the 214th meeting of the Electrochemical Society above

  8. CD36/SR-B2-TLR2 Dependent Pathways Enhance Porphyromonas gingivalis Mediated Atherosclerosis in the Ldlr KO Mouse Model.

    Directory of Open Access Journals (Sweden)

    Paul M Brown

    Full Text Available There is strong epidemiological association between periodontal disease and cardiovascular disease but underlying mechanisms remain ill-defined. Because the human periodontal disease pathogen, Porphyromonas gingivalis (Pg, interacts with innate immune receptors Toll-like Receptor (TLR 2 and CD36/scavenger receptor-B2 (SR-B2, we studied how CD36/SR-B2 and TLR pathways promote Pg-mediated atherosclerosis. Western diet fed low density lipoprotein receptor knockout (Ldlr° mice infected orally with Pg had a significant increase in lesion burden compared with uninfected controls.This increase was entirely CD36/SR-B2-dependent, as there was no significant change in lesion burden between infected and uninfected Cd36o/Ldlro mice [corrected]. Western diet feeding promoted enhanced CD36/SR-B2-dependent IL1β generation and foam cell formation as a result of Pg lipopolysaccharide (PgLPS exposure. CD36/SR-B2 and TLR2 were necessary for inflammasome activation and optimal IL1ß generation, but also resulted in LPS induced lethality (pyroptosis. Modified forms of LDL inhibited Pg-mediated IL1ß generation in a CD36/SR-B2-dependent manner and prevented pyroptosis, but promoted foam cell formation. Our data show that Pg infection in the oral cavity can lead to significant TLR2-CD36/SR-B2 dependent IL1ß release. In the vessel wall, macrophages encountering systemic release of IL1ß, PgLPS and modified LDL have increased lipid uptake, foam cell formation, and release of IL1ß, but because pyroptosis is inhibited, this enables macrophage survival and promotes increased plaque development. These studies may explain increased lesion burden as a result of periodontal disease, and suggest strategies for development of therapeutics.

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

    NARCIS (Netherlands)

    Konijnendijk, W.L.; Blasse, G.


    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 cluster

  10. 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


    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.

  11. The role of Ephs, Ephrins, and growth factors in Kaposi sarcoma and implications of EphrinB2 blockade


    Scehnet, Jeffrey S.; Ley, Eric J.; Krasnoperov, Valery; Liu, Ren; Manchanda, Parmeet K.; Sjoberg, Eric; Kostecke, Anna P.; Gupta, Sachin; Kumar, S. Ram; Gill, Parkash S.


    Kaposi sarcoma (KS) is associated with human herpesvirus (HHV)-8 and is dependent on the induction of vascular endothelial growth factors (VEGFs). VEGF regulates genes that provide arterial or venous identity to endothelial cells, such as the induction of EphrinB2, which phenotypically defines arterial endothelial cells and pericytes, and represses EphB4, which defines venous endothelial cells. We conducted a comprehensive analysis of the Eph receptor tyrosine kinases to determine which membe...

  12. Cleavage of kininogen and subsequent bradykinin release by the complement component: mannose-binding lectin-associated serine protease (MASP-1.

    Directory of Open Access Journals (Sweden)

    József Dobó

    Full Text Available Bradykinin (BK, generated from high-molecular-weight kininogen (HK is the major mediator of swelling attacks in hereditary angioedema (HAE, a disease associated with C1-inhibitor deficiency. Plasma kallikrein, activated by factor XIIa, is responsible for most of HK cleavage. However other proteases, which activate during episodes of angioedema, might also contribute to BK production. The lectin pathway of the complement system activates after infection and oxidative stress on endothelial cells generating active serine proteases: MASP-1 and MASP-2. Our aim was to study whether activated MASPs are able to digest HK to release BK. Initially we were trying to find potential new substrates of MASP-1 in human plasma by differential gel electrophoresis, and we identified kininogen cleavage products by this proteomic approach. As a control, MASP-2 was included in the study in addition to MASP-1 and kallikrein. The proteolytic cleavage of HK by MASPs was followed by SDS-PAGE, and BK release was detected by HPLC. We showed that MASP-1 was able to cleave HK resulting in BK production. MASP-2 could also cleave HK but could not release BK. The cleavage pattern of MASPs is similar but not strictly identical to that of kallikrein. The catalytic efficiency of HK cleavage by a recombinant version of MASP-1 and MASP-2 was about 4.0×10(2 and 2.7×10(2 M(-1 s(-1, respectively. C1-inhibitor, the major inhibitor of factor XIIa and kallikrein, also prevented the cleavage of HK by MASPs. In all, a new factor XII- and kallikrein-independent mechanism of bradykinin production by MASP-1 was demonstrated, which may contribute to the pro-inflammatory effect of the lectin pathway of complement and to the elevated bradykinin levels in HAE patients.

  13. High-resolution photoemission study of MgB2. (United States)

    Takahashi, T; Sato, T; Souma, S; Muranaka, T; Akimitsu, J


    We have performed high-resolution photoemission spectroscopy on MgB2 and observed opening of a superconducting gap with a narrow coherent peak. We found that the superconducting gap is s like with the gap value ( Delta) of 4.5+/-0.3 meV at 15 K. The temperature dependence (15-40 K) of the gap value follows well the BCS form, suggesting that 2Delta/k(B)T(c) at T = 0 is about 3. No pseudogap behavior is observed in the normal state. The present results strongly suggest that MgB2 is categorized into a phonon-mediated BCS superconductor in the weak-coupling regime.

  14. Evidence for two superconducting gaps in MgB2. (United States)

    Chen, X K; Konstantinovic, M J; Irwin, J C; Lawrie, D D; Franck, J P


    We have measured the Raman spectra of polycrystalline MgB2 from 25 to 1200 cm(-1). A superconductivity-induced redistribution in the electronic Raman continuum was observed. Two pair-breaking peaks appear in the spectra, suggesting the presence of two superconducting gaps. The measured spectra were analyzed using a quasi-two-dimensional model in which two s-wave superconducting gaps open on two sheets of Fermi surface. For the gap values we have obtained Delta(1) = 22 cm(-1) ( 2.7 meV) and Delta(2) = 50 cm(-1) ( 6.2 meV). Our results suggest that a conventional phonon-mediated pairing mechanism occurs in the planar boron sigma bands and is responsible for the superconductivity of MgB2.

  15. Attempts at doping indium in MgB2 (United States)

    Grivel, J.-C.


    Indium (In) doped MgB2 polycrystalline samples were prepared by solid-liquid phase reaction in Ar. After reaction at 800 °C, less than 1 at.% Mg was replaced by In in the MgB2 phase, without significant influence on its lattice parameters and only a slight decrease of its superconducting transition temperature. For all studied In concentrations in the nominal composition, the formation of InMg was evidenced by X-ray diffraction. The critical current density and accommodation field of the wires are decreased in the samples containing In. The flux pinning mechanism can be described by surface pinning in both the doped and undoped samples.

  16. Permanent magnet with MgB2 bulk superconductor (United States)

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


    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 (cryocoolers, making MgB2 bulks promising for the next generation of Tesla-class permanent-magnet applications.

  17. B2B Integration in Global Supply Chains

    DEFF Research Database (Denmark)

    Schubert, Petra; Legner, Christine


    The competitiveness of businesses is increasingly dependent on their electronic networks with customers, suppliers, and partners. While the strategic and operational impact of external integration and IOS adoption has been extensively studied, much less attention has been paid to the organizational...... and technical design of electronic relationships. The objective of our longitudinal research project is the development of a framework for understanding and explaining B2B integration. Drawing on existing literature and empirical cases we present a reference model (a classification scheme for B2B Integration...... 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....

  18. 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...... 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 the crowd, motivation of the crowd, and actual activities in reaching the crowd. Managing the input from the crowd is regarded as a later stage in the overall innovation management but also as a focal point in the arguments for improving B2B crowdsourcing. In crowd selection processes this paper aims...

  19. Heterostructures of Bi-4334 and MgB2 superconductors (United States)

    Padmavathi, M.; Singh, R.


    We report the studies on hetero structures of Bi-4334 and MgB2 superconductors. The two superconductors were arranged in the form of bulk multilayers using hydraulic pressure system. X-ray diffraction pattern and dc magnetization studies confirm the presence of both superconducting phases in this try-layer hetero structured sample. The d.c magnetization shows the superconducting onset at 77K and 39K for Bi-4334 and MgB2 phases respectively. Critical current density (Jc) is calculated from hysteresis loop of the sample in both in-plane field and out of plane field configurations. Inverted anisotropy in Jc is observed due to enhancement of ab-plane properties because of multilayer growth process. Morphology of the samples at surface and interface of two superconducting layers is discussed in view of Field emission scanning electron microscopy.

  20. Superconductivity in MgB2 irradiated with energetic protons (United States)

    Sandu, Viorel; Craciun, Liviu; Ionescu, Alina Marinela; Aldica, Gheorghe; Miu, Lucica; Kuncser, Andrei


    A series of MgB2 samples were irradiated with protons of 11.3 and 13.2 MeV. Magnetization data shows an insignificant reduction of the critical temperatures but a continuous decrease of the Meissner fraction with increasing fluence or energy. All samples show a consistent improvement of the critical current density compared to the virgin sample and an increase of the pinning energy at high fields as resulted from relaxation data.

  1. B2B Models for DoD Acquisition (United States)


    business (B2B) e- commerce refers to transactions between businesses conducted electronically over the Internet, intranets, extranets, or private...types of electronic marketplace participation: 1) Sell-side, 2) Buy- side, 3) Exchanges, and 4) Collaborative commerce . In sell-side commerce , there...types are collectively referred to as company-centric electronic commerce , because they address a single company buying or selling needs. Exchanges

  2. Inbound-markkinoinnin opas pienille B2B-asiantuntijayrityksille


    Halonen, Tuija


    Digitalisaatio on muuttanut asiakkaiden ostokäyttäytymistä, minkä vuoksi myös markkinoinnin on muututtava. Asiakaslähtöinen inbound-markkinointi on vetovoimainen vaihtoehto perinteiselle yksisuuntaiselle markkinoinnille, jonka teho on laskussa. Tämän toiminnallisen opinnäytetyön tarkoituksena oli rakentaa opas, joka auttaa pieniä suomalaisia B2B-asiantuntijayrityksiä suunnittelemaan ja toteuttamaan toimivaa ja kustannustehokasta inbound-markkinointia. Teoreettisen viitekehyksen pohjal...

  3. Performance and Applications of L1B2 Ultrasonic Motors


    Gal Peled; Roman Yasinov; Nir Karasikov


    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...

  4. Itinerant magnetism in CeRh3B2



    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 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.

  5. Itinerant magnetism in CeRh3B2 (United States)

    Eriksson, Olle; Johansson, Börje; Brooks, M. S. S.; Skriver, H. L.; Sjöström, Jörgen


    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 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.

  6. 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


    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.

  7. Biotechnological production of vitamin B2-enriched bread and pasta. (United States)

    Capozzi, Vittorio; Menga, Valeria; Digesu, Anna Maria; De Vita, Pasquale; van Sinderen, Douwe; Cattivelli, Luigi; Fares, Clara; Spano, Giuseppe


    Lactic acid bacteria (LAB) were obtained from durum wheat flour samples and screened for roseoflavin-resistant variants to isolate natural riboflavin-overproducing strains. Two riboflavin-overproducing strains of Lactobacillus plantarum isolated as described above were used for the preparation of bread (by means of sourdough fermentation) and pasta (using a prefermentation step) to enhance their vitamin B2 content. Pasta was produced from a monovarietal semolina obtained from the durum wheat cultivar PR22D89 and, for experimental purposes, from a commercial remilled semolina. Several samples were collected during the pasta-making process (dough, extruded, dried, and cooked pasta) and tested for their riboflavin content by a high-performance liquid chromatography method. The applied approaches resulted in a considerable increase of vitamin B2 content (about 2- and 3-fold increases in pasta and bread, respectively), thus representing a convenient and efficient food-grade biotechnological application for the production of vitamin B2-enriched bread and pasta. This methodology may be extended to a wide range of cereal-based foods, feed, and beverages. Additionally, this work exemplifies the production of a functional food by a novel biotechnological exploitation of LAB in pasta-making.

  8. Modernization of B-2 Data, Video, and Control Systems Infrastructure (United States)

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


    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.

  9. Agent-based services for B2B electronic commerce (United States)

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


    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.

  10. Clinical endocrinology and metabolism. Receptors for gut peptides. (United States)

    Harmar, Anthony J


    Most gut peptides exert their effects through G protein-coupled receptors, a family of about 700 membrane proteins, 87 of which are presently known to have peptide ligands. Three additional gut peptide receptors are not G protein-coupled receptors but regulate intracellular cyclic GMP accumulation. The aim of this review is to illustrate how the sequencing of the human genome and other recent advances in genomics has contributed to our understanding of the role of peptides and their receptors in gastrointestinal function. Recent discoveries include the identification of receptors for the peptides motilin and neuromedin U, and new physiological ligands for the PTH2 receptor, the CRF(2) receptor and the growth hormone secretagogue receptor. Knockout mice lacking specific peptide receptors or their ligands provide informative animal models in which to determine the functions of the numerous peptide-receptor systems in the gut and to predict which of them may be the most fruitful for drug development. Some peptide-receptor signalling systems may be more important in disease states than they are in normal physiology. For example, substance P, galanin, bradykinin and opioids play important roles in visceral pain and inflammation. Other peptides may have developmental roles: for example, disruption of endothelin-3 signalling prevents the normal development of the enteric nervous system and contributes to the pathogenesis of Hirschsprung disease.

  11. B2幅面的数码印刷机市场%The B2 Digital Press Market

    Institute of Scientific and Technical Information of China (English)

    Andrew Tribute


    @@ B2幅面单张纸数码印刷机看起来可能是印刷机制造商的圣杯.在20世纪90年代,Indigo定期在各个印刷展览会上推出未来B2幅面印刷机的样机.问题是,Indigo(未并入惠普以前)始终没能为印刷机开发出一个成像引擎.这样的话,展出的只是问题而不是解决方案.大多数单张纸数码印刷机的最大成像宽度可以达到14英寸(约35cm).

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

    Energy Technology Data Exchange (ETDEWEB)

    Alper, O.; Yamaguchi, K.; Hitomi, J.; Honda, S.; Matsushima, T.; Abe, K. (National Cancer Center Research Institute, Tokyo (Japan))


    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.

  13. C-erbB-2 onco-protein expression in breast cancer: relationship to tumour characteristics and short-term survival in Universiti Kebansaan Malaysia Medical Centre. (United States)

    Sharifah, N A; Lee, B R; Clarence-Ko, C H; Tan, G C; Shiran, M S; Naqiyah, I; Rohaizak, M; Fuad, I; Tamil, A M


    Breast cancer is the commonest cancer affecting females in Malaysia, contributing 31% of all newly diagnosed cases amongst Malaysian women. The present retrospective cohort study evaluated the relationship between cerbB- 2 onco-protein overexpression with various tumour characteristics and survival rate of breast cancer patients treated at the Universiti Kebangsaan Malaysia Medical Centre (UKMMC) between 1996-2000. CerbB- 2 oncoprotein overexpression was determined by immunohistochemistry (IHC) and tumors showing 2+ positivity were verified by Fluorescence In Situ Hybridization (FISH). One hundred and seventy two patients were eligible for the study with a short-term follow-up (median) of 5.1 years. C-erbB-2 oncoprotein overexpression correlated with lymph node positivity, oestrogen receptor (ER) and progesterone receptor (PR) negativity. Univariate analyses showed shorter disease free survival (DFS) and overall survival (OS) in patients with cerbB- 2 oncoprotein overexpression, Malay ethnicity, higher tumour grade, lymph node positivity, ER and PR negativity. In a subgroup of patients with c-erbB-2 oncoprotein overexpression, a shorter OS was observed in those with lymph node positivity, ER and PR negativity. In multivariate prognostic analysis, lymph node status, ER status and tumour grading were the strongest independent prognostic factors for both OS and DFS. However, c-erbB-2 status was not a significantly independent prognostic factor, even in subsets with lymph node positive or negative group. C-erbB-2 oncoprotein overexpression correlated well with lymph node status, ER and PR. Shorter OS and DFS were significantly observed in patients with c-erbB-2 oncoprotein overexpression. Lymph node status, ER status and tumour grading were the only three independent prognostic factors for OS and DFS in this study. Although c-erbB-2 expression is obviously important from a biological standpoint, multivariate analysis showed that it is not an independent prognostic

  14. Receptors for enterovirus 71


    Yamayoshi, Seiya; Fujii, Ken; Koike, Satoshi


    Enterovirus 71 (EV71) is one of the major causative agents of hand, foot and mouth disease (HFMD). Occasionally, EV71 infection is associated with severe neurological diseases, such as acute encephalitis, acute flaccid paralysis and cardiopulmonary failure. Several molecules act as cell surface receptors that stimulate EV71 infection, including scavenger receptor B2 (SCARB2), P-selectin glycoprotein ligand-1 (PSGL-1), sialylated glycan, heparan sulfate and annexin II (Anx2). SCARB2 plays crit...

  15. 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


    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.

  16. Superconductivity in MgB2: clean or dirty? (United States)

    Mazin, I I; Andersen, O K; Jepsen, O; Dolgov, O V; Kortus, J; Golubov, A A; Kuz'menko, A B; Van Der Marel, D


    A large number of experimental facts and theoretical arguments favor a two-gap model for superconductivity in MgB2. However, this model predicts strong suppression of the critical temperature by interband impurity scattering and, presumably, a strong correlation between the critical temperature and the residual resistivity. No such correlation has been observed. We argue that this fact can be understood if the band disparity of the electronic structure is taken into account, not only in the superconducting state, but also in normal transport.

  17. Phonon dispersion and lifetimes in MgB2. (United States)

    Shukla, Abhay; Calandra, Matteo; D'Astuto, Matteo; Lazzeri, Michele; Mauri, Francesco; Bellin, Christophe; Krisch, Michael; Karpinski, J; Kazakov, S M; Jun, J; Daghero, D; Parlinski, K


    We measure phonon dispersion and linewidth in a single crystal of MgB2 along the Gamma-A, Gamma-M, and A-L directions using inelastic x-ray scattering. We use density functional theory to compute the effect of both electron-phonon coupling and anharmonicity on the linewidth, obtaining excellent agreement with experiment. Anomalous broadening of the E(2g) phonon mode is found all along Gamma-A. The dominant contribution to the linewidth is always the electron-phonon coupling.

  18. Two-band superconductivity in MgB2. (United States)

    Iavarone, M; Karapetrov, G; Koshelev, A E; Kwok, W K; Crabtree, G W; Hinks, D G; Kang, W N; Choi, Eun-Mi; Kim, Hyun Jung; Kim, Hyeong-Jin; Lee, S I


    The study of the anisotropic superconductor MgB2 using a combination of scanning tunneling microscopy and spectroscopy reveals two distinct energy gaps at Delta(1)=2.3 meV and Delta(2)=7.1 meV at 4.2 K. Different spectral weights of the partial superconducting density of states are a reflection of different tunneling directions in this multiband system. Temperature evolution of the tunneling spectra follows the BCS scenario [Phys. Rev. Lett. 3, 552 (1959)

  19. Strategic Insights from Mystery Shopping in B2B Relationships

    DEFF Research Database (Denmark)

    Mattsson, Jan


    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...... guideline covering the themes of map, smoke and mirror as metaphors) has been extended to comprise a larger group of engineers and may be taken up in a company-wide way. The experiment was deemed effective in developing both a procedure for mystery shopping and a new way to train the consultants....

  20. 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


    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.

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

    DEFF Research Database (Denmark)

    Fast, Søren; Henningsen, Emil; Bygum, Anette


    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....

  2. Characterization of MgB2 Superconducting Hot Electron Bolometers (United States)

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


    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.

  3. Multilayer MgB2 superconducting quantum interference filter magnetometers (United States)

    Galan, Elias; Melbourne, Thomas; Davidson, Bruce A.; Xi, X. X.; Chen, Ke


    We report two types of all-MgB2 superconductive quantum interference filter (SQIF) magnetometers that can measure absolute magnetic fields with high sensitivity. In one configuration, the SQIFs were made of 20 multilayer nonplanar all-MgB2 superconducting quantum interference devices (SQUIDs) connected in parallel with loop areas ranging in size from 0.4 to 3.6 μm2. These devices are sensitive to magnetic fields parallel to the substrate and show a single antipeak from 3 to 16 K with a maximum transfer function of ˜16 V/T at 3 K and a field noise of ˜110 pT/Hz1/2 above 100 Hz at 10 K. In a second configuration, the SQIFs were made with 16 planar SQUIDs connected in parallel with loop areas ranging in size from 4 μm2 to 25 μm2 and are sensitive to the magnetic fields perpendicular to the substrate. The planar SQIF shows a single antipeak from 10 to 22 K with a maximum transfer function of 7800 V/T at 10 K and a field noise of ˜70 pT/Hz1/2 above 100 Hz at 20 K.

  4. Low-noise THz MgB2 Josephson mixer (United States)

    Cunnane, Daniel; Kawamura, Jonathan H.; Acharya, Narendra; Wolak, Matthäus A.; Xi, X. X.; Karasik, Boris S.


    The potential applications for high frequency operation of the Josephson effect in MgB2 include THz mixers, direct detectors, and digital circuits. Here we report on MgB2 weak links which exhibit the Josephson behavior up to almost 2 THz and using them for low-noise heterodyne detection of THz radiation. The devices are made from epitaxial film grown in the c-axis direction by the hybrid physical-chemical vapor deposition method. The current in the junctions travels parallel to the surface of the film, thus making possible a large contribution of the quasi-two-dimensional σ-gap in transport across the weak link. These devices are connected to a planar spiral antenna with a dielectric substrate lens to facilitate coupling to free-space radiation for use as a detector. The IcRn product of the junction is 5.25 mV, giving confirmation of a large gap parameter. The sensitivity of the mixer was measured from 0.6 THz to 1.9 THz. At a bath temperature of over 20 K, a mixer noise temperature less than 2000 K (DSB) was measured near 0.6 THz.

  5. Detection of amino acetonitrile in Sgr B2(N)

    CERN Document Server

    Belloche, A; Comito, C; Müller, H S P; Schilke, P; Ott, J; Thorwirth, S; Hieret, C


    Amino acids are building blocks of proteins and therefore key ingredients for the origin of life. The simplest amino acid, glycine, has long been searched for in the interstellar medium but has not been unambiguously detected so far. Since the search for glycine has turned out to be extremely difficult, we aimed at detecting a chemically related species (possibly a direct precursor), amino acetonitrile. With the IRAM 30m telescope we carried out a complete line survey of the hot core regions Sgr B2(N) and (M) in the 3 mm range, plus partial surveys at 2 and 1.3 mm. We analyzed our 30m line survey in the LTE approximation and modeled the emission of all known molecules simultaneously. We identified spectral features at the frequencies predicted for amino acetonitrile lines having intensities compatible with a unique rotation temperature. We also used the VLA to look for cold, extended emission from amino acetonitrile. We detected amino acetonitrile in Sgr B2(N) in our 30m telescope line survey and conducted co...

  6. Preparation of highly preferred orientation TiB2 coatings

    Institute of Scientific and Technical Information of China (English)


    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.

  7. Vortex Lattice Transition Dynamics in MgB2 (United States)

    Rastovski, C.; Das, P.; Schlesinger, K.; Eskildsen, M. R.; Gannon, W. J.; Dewhurst, C. D.; Zhigadlo, N. D.; Karpinski, J.


    We present small-angle neutron scattering (SANS) studies of the vortex lattice (VL) in MgB2 with H c. This material has three different VL phases, all with triangular symmetry but oriented differently with respect to the crystalline axes. Furthermore, a high degree of metastability between the VL phases of MgB2 has been observed as the sample is cooled or heated across the equilibrium phase transitions. Here we present detailed studies of how the metastable (MS) VL phases transition to the ground state (GS), either driven by small changes of the DC magnetic field or by a transverse AC field. Our results show that the MS VL is not due to vortex pinning, and results are inconsistent with predictions based on the Bean model. Instead, we speculate that a ``jamming'' of counter rotated VL domains is responsible for the VL metastability. This is further supported by a power law dependence of the GS VL domain population upon the number of applied AC cycles. This work was supported by the Department of Energy, Basic Energy Sciences under Award No. DE-FG02-10ER46783.

  8. Interação entre Hb B2 e Hb S Interaction between Hb B2 and Hb S

    Directory of Open Access Journals (Sweden)

    Natália Ferreira


    Full Text Available As hemoglobinopatias e talassemias constituem as afecções genéticas mais comuns, apresentando-se, na maioria dos casos, em heterozigose. Diante da diversidade de hemoglobinas variantes encontrada na população brasileira, metodologias específicas e complementares para um diagnóstico laboratorial preciso, capaz de elucidar possíveis interações entre estas variantes genéticas, são necessárias. Este relato de caso descreve a interação entre hemoglobina B2 e a hemoglobina S em um indivíduo do sexo feminino, caucasoide, proveniente da região Sudeste do Brasil, identificada por meio de técnicas eletroforéticas em diferentes pH, cromatografia líquida de alta performance e PCR- RFLP. Visto que a hemoglobina B2 coelui com a hemoglobina S na análise cromatográfica e dificilmente é visualizada em eletroforese pH alcalino, devido à sua baixa concentração, justifica-se a necessidade da associação de testes laboratoriais, inclusive moleculares, na rotina do diagnóstico de hemoglobinas para a correta identificação do perfil de hemoglobinas do indivíduo e real frequência na população brasileira. Rev. Bras. Hematol. Hemoter.Hemoglobinopathies and thalassemias are the most common genetic diseases, and in most cases, present as heterozygous. Due to the diversity of hemoglobin variants, specific and complementary methodologies are necessary for a precise laboratorial diagnosis, able to elucidate possible interactions between genetic polymorphisms. This case report describes an interaction between hemoglobin B2 and hemoglobin S in a Caucasian woman from the southeastern region of Brazil. This interaction was identified by electrophoresis in different pHs, high performance liquid chromatography and PCR-RFLP. As hemoglobin B2 is eluted in the same window as hemoglobin S in automatic HPLC systems and is hardly seen in alkaline electrophoresis due to its low concentration, the association must be confirmed using additional laboratorial

  9. Novel Functions of NF-kappaB2/p52 in Androgen Receptor Signaling in CRPC (United States)


    mM Hepes (pH 7.9), 0.25 M NaCl, 1% Nonidet P - 40 , and 1 mM EDTA with protease inhibitors, and total protein in the lysates was determined with the...Cells were lysed in a high-salt buffer containing 10 mM Hepes (pH 7.9), 0.25 M NaCl, 1% Nonidet P - 40 , and 1 mM EDTA with protease inhibitors, and...with PSA-E/ P -Luc reporter, empty vector or p52 together with siRNAs against FL AR or AR-V7. Cells were treated with 0 or 40 µM Enzalutamide and

  10. 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


    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.

  11. Effects of Porphyromonas gingivalis lipopolysaccharide on osteoblast-osteoclast bidirectional EphB4-EphrinB2 signaling. (United States)

    Zhang, Yi; Wang, Xi-Chao; Bao, Xing-Fu; Hu, Min; Yu, Wei-Xian


    In bone remodeling, the Eph family is involved in regulating the process of osteoclast and osteoblast coordination in order to maintain bone homeostasis. In this study, the effects of Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) on the osteoblast-osteoclast bidirectional EphB4-EphrinB2 signaling were investigated. An osteoblast-osteoclast co-culture system was achieved successfully. Hence, direct contact and communication between osteoblasts and osteoclasts was permitted. Regarding the protein expression and gene expression of EphB4 and EphrinB2, it was shown that Pg-LPS increased the expression of EphB4 while inhibiting the expression of EphrinB2. Therefore, the results indicate that, when treated with Pg-LPS, the EphB4 receptor on osteoblasts and the EphrinB2 ligand on osteoclasts may generate bidirectional anti-osteoclastogenic and pro-osteoblastogenic signaling into respective cells and potentially facilitate the transition from bone resorption to bone formation. This study may contribute to the control of osteoblast differentiation and bone formation at remodeling, and possibly also modeling, sites.

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

    CERN Document Server

    Bhatia, Krishnaprem; Perlovsky, Alan


    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.

  13. Combustion Synthesis of TiB2 Ceramics Powder from B2O3-TiO2-Mg System in Air Atmosphere

    Institute of Scientific and Technical Information of China (English)

    HE Jinyun; WANG Weimin; FU Zhengyi; SUN Hui


    TiB2 ceramics powder was synthesized from B2O3-TiO2-Mg system. The effects of TiB2 addition as diluent on the combustion synthesis process were investigated. The results of thermodynamic calculation and experiments show that the increase of TiB2 content ranging from 0 to 20wt% can reduce the adiabatic temperature Tad from 3100 K to 2896 K and combustion temperature Tc from 2139 K to 1621 K respectively. The particle size and half width of the particle distribution are also increased with the addition of TiB2 increasing from 0 to 20wt%. The combustion product is a mixture of TiB2, MgO, and other intermediate phases. The leached product contains mainly TiB2, TiO2 and TiN, and its oxygen content is 7.77wt%.

  14. Sulla razionalità delle 3-varietà di Fano con B_2 almeno 2

    Directory of Open Access Journals (Sweden)

    Alberto Alzati


    Full Text Available Complex, smooth, projective Fano varieties were classified by Iskovskih when B2 =1 (B2 is the second Betti number and by Mori and Mukai when B2  is at least 2. When B2 =1 it is known if such varieties are rational (unirational or not; in this paper we solve this problem when B2  greater or equal 2.

  15. Structural and thermodynamic properties of AlB2 compound

    Institute of Scientific and Technical Information of China (English)

    Zhou Xiao-Lin; Liu Ke; Chen Xiang-Rong; Zhu Jun


    We employ a first-principles plane wave method with the relativistic analytic pseudopotential of Hartwigsen,Goedecker and Hutter (HGH) scheme in the frame of DFT to calculate the equilibrium lattice parameters and the thermodynamic properties of AlB2 compound with hcp structure. The obtained lattice parameters are in good agreement with the available experimental data and those calculated by others. Through the quasi-harmonic Dcbye model, obtained successfully are the dependences of the normalized lattice parameters a/a0 and c/c0 on pressure P, the normalized primitive cell volume V/Vo on pressure P, the variation of the thermal expansion α with pressure P and temperature T, as well as the Debye temperature θD and the heat capacity CV on pressure P and temperature T.

  16. Scanning tunneling spectroscopy in MgB2. (United States)

    Karapetrov, G; Iavarone, M; Kwok, W K; Crabtree, G W; Hinks, D G


    We present scanning tunneling microscopy measurements of the surface of superconducting MgB2 with a critical temperature of 39 K. In zero magnetic field the conductance spectra can be analyzed in terms of the standard BCS theory with a smearing parameter gamma. The value of the superconducting gap is 5 meV at 4.2 K, with no experimentally significant variation across the surface of the sample. The temperature dependence of the gap follows the BCS form, fully consistent with phonon-mediated superconductivity in this novel superconductor. The application of a magnetic field induces strong pair breaking as seen in the conductance spectra in fields up to 6 T.

  17. Relationship Quality as Predictor of B2B Customer Loyalty

    Directory of Open Access Journals (Sweden)

    Shaimaa S. B. Ahmed Doma


    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.

  18. 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


    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.

  19. Vortex lattice transitions in YNi2B2C

    Indian Academy of Sciences (India)

    S J Levett; C D Dewhurst; D McK Paul


    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.

  20. Semantic ETL into i2b2 with Eureka! (United States)

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


    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.

  1. Performance and Applications of L1B2 Ultrasonic Motors

    Directory of Open Access Journals (Sweden)

    Gal Peled


    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.

  2. Effects of Neuregulins on Invasion and Metastasis of Non-overexpression ErbB2 Breast Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    Ya-mei Zhang; Ting-ting Zhao; Hua-yu Deng


    Objective: To explore the effects of neuregulins on ErbB2 receptor signal transduction pathway activation, and invasion and metastasis of non-overexpression ErbB2 breast cancer cell MDA-MB-231. Methods: The expressions of neuregulin were detected by immunocytochemistry and Western blot. MDA-MB-231 cells were treated with ErbB2 kinase inhibitor AG825. Proliferations were measured with MTT assay. Invasion and metastasis of MDA-ME-231 cells were evaluated with transwell chamber. The enzyme activities of MMP-2 and MMP-9 were detected by gelatin zymography. The expressions of MMP-2 and HIF-1α were detected by Western blot.Results: MDA-MB-231 cells expressed a relatively higher level of neuregulin. In Western blot, the positive reaction band was found at 44KD which coincides with the molecular weight of NRG. When MDA-MB-231 cells were treated with AG825, the proliferation was inhibited in a time-dose-dependent manner (P<0.01), invasion and metastasis were also depressed (P<0.05). The enzyme activities of MMP-2 and MMP-9 were lower (P<0.05). The expression levels of MMP-2 and HIF-1α were decreased (P<0.05).Conclusion: Our study indicates that neuregulins are synthesized in MDA-MB-231 cells as transmembrane proteins, neuregulins could activate ErbB2 receptor signal transduction pathway by autocrine or paracrine secretion, and induce invasion and metastasis of MDA-MB-231 cells.

  3. Effect of TiB2 content on resistance to sodium penetration of TiB2/C cathode composites for aluminium electrolysis

    Institute of Scientific and Technical Information of China (English)

    李劼; 方静; 李庆余; 赖延清


    TiB2/C cathode composites with various contents of TiB2 were prepared and their characterizations were observed and compared. The expansion of samples due to sodium and bath penetration was tested with a modified laboratory Rapoport apparatus and the appearances of the cut sections of specimens after electrolysis were studied.The results show that the mass of TiB2/C cathode composites with mass fraction of TiB2 less than 70 % appreciably increases, but that of the composites with mass fraction of TiB2 more than 70% decreases slightly after being baked.The resistance to sodium and bath penetration of TiB2/C cathode composites increases with the increase of TiB2 content, especially in the composites with high TiB2 content. TiB2/C cathode composites have high resistance to the penetration of sodium and bath as well as good wettability by molten aluminum, and keep integrality and have little change of appearance after electrolysis, which indicates that TiB2/C cathode composites can be used as inert wettable cathode for aluminum electrolysis.

  4. Bond deformation paths and electronic instabilities of ultraincompressible transition metal diborides: Case study of OsB2 and IrB2 (United States)

    Zhang, R. F.; Legut, D.; Wen, X. D.; Veprek, S.; Rajan, K.; Lookman, T.; Mao, H. K.; Zhao, Y. S.


    The energetically most stable orthorhombic structure of OsB2 and IrB2 is dynamically stable for OsB2 but unstable for IrB2. Both diborides have substantially lower shear strength in their easy slip systems than their metal counterparts. This is attributed to an easy sliding facilitated by out-of-plane weakening of metallic Os-Os bonds in OsB2 and by an in-plane bond splitting instability in IrB2. A much higher shear resistance of Os-B and B-B bonds than Os-Os ones is found, suggesting that the strengthened Os-B and B-B bonds are responsible for hardness enhancement in OsB2. In contrast, an in-plane electronic instability in IrB2 limits its strength. The electronic structure of deformed diborides suggests that the electronic instabilities of 5d orbitals are their origin of different bond deformation paths. Neither IrB2 nor OsB2 can be intrinsically superhard.

  5. Differential modulation of bradykinin-induced relaxation of endothelin-1 and phenylephrine contractions of rat aorta by antioxidants

    Institute of Scientific and Technical Information of China (English)

    Ogechukwu ANOZIE; Richonda ROSS; Adebayo O OYEKAN; Momoh A YAKUBU


    Aim: We tested the hypothesis that bradykinin (BK)-induced relaxation of phenylephrine (PE) and endothelin-1 (ET-1) contractions can be differentially modulated by reactive oxygen species (ROS). Methods: Aortic rings isolated from Sprague-Dawley rats were used for the study. The contribution of ROS to PE(1×10-9-1×10-5 mol/L)- and ET-1 (1×10-10-1×10-8 mol/L)-induced contractions and the influence of ROS in B K (1×10-9-1×10mol/L) relaxation of PE (1×10-7 mol/L) or ET-1 (1×10-9 mol/L)-induced tension was evaluated in the aorta in the presence or absence of the following antioxidants: catalase (CAT, 300 U/mL), superoxide dismutase (SOD, 300 U/mL), and vitamin C (1×10-4 mol/L). Results: Tension generated by ET-1 (1 × 10-9 mol/L) or PE (1 × 10-7 mol/L) was differentially relaxed by BK(1 × 10-5 mol/L), producing a maximal relaxation of 75 %±5 % and 35±4%, respectively.The BK (1×10-5 mol/L)-induced relaxation of PE (1×10-7 mol/L) tension was signifi-cantly enhanced from 35%±4% (control) to 56%±9%, 60%±5%, and 49%±6% by SOD, CAT, and vitamin C, respectively (P<0.05, n=8). However, the relaxation of ET-1 (1×10-9 mol/L) tension was significantly attenuated from 75%±5% (control)to 37%±9%, 63%±4%, and 39%±7% by SOD, CAT, and vitamin C, respectively(P<0.05, n=8). On the other hand, CAT had no effect on PE-induced tension, while SOD enhanced PE-induced tension (36%,P<0.05, n=10) and vitamin C attenuated(66%, P<0.05, n=8) the tension induced by PE. By contrast, SOD or vitamin C had no effect, but CAT attenuated (44%, P<0.05, n=9) the tension induced by ET-1.Conclusion: We have demonstrated that O2- and H2O2 differentially modulate BK relaxation in an agonist-specific manner. O2- attenuates BK-induced relaxation of PE contraction, but contributes to the relaxation of ET-1 contraction. O2- seems to inhibit PE contraction, while H2O2 contributes to ET-1-induced contraction. Thus,ROS differentially modulate vascular tone depending on the vasoactive agent that

  6. The conserved nhaAR operon is drastically divergent between B2 and non-B2 Escherichia coli and is involved in extra-intestinal virulence. (United States)

    Lescat, Mathilde; Reibel, Florence; Pintard, Coralie; Dion, Sara; Glodt, Jérémy; Gateau, Cecile; Launay, Adrien; Ledda, Alice; Cruveiller, Stephane; Cruvellier, Stephane; Tourret, Jérôme; Tenaillon, Olivier


    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.

  7. High-temperature vaporization of B2O3(l) under reducing conditions. (United States)

    Jacobson, Nathan S; Myers, Dwight L


    The vaporization of B(2)O(3) in a reducing environment leads to the formation of both B(2)O(3)(g) and B(2)O(2)(g). Whereas the formation of B(2)O(3)(g) is well understood, many questions about the formation of B(2)O(2)(g) remain. Previous studies using B(s) + B(2)O(3)(l) have led to inconsistent thermodynamic data. In this study, it was found that, after heating, B(s) and B(2)O(3)(l) appeared to separate and variations in contact area likely led to the inconsistent vapor pressures of B(2)O(2)(g). To circumvent this problem, the activity of boron was fixed with a two-phase mixture of FeB and Fe(2)B. Both second- and third-law enthalpies of formation were measured for B(2)O(2)(g) and B(2)O(3)(g). From these values, the enthalpies of formation at 298.15 K were calculated to be -479.9 ± 25.7 kJ/mol for B(2)O(2)(g) and -833.4 ± 13.1 kJ/mol for B(2)O(3)(g). Ab initio calculations to determine the enthalpies of formation of B(2)O(2)(g) and B(2)O(3)(g) were conducted using the W1BD composite method and showed good agreement with the experimental values.

  8. Lattice Thermal Conductivity of Ultra High Temperature Ceramics (UHTC) ZrB2 and HfB2 from Atomistic Simulations (United States)

    Lawson, JOhn W.; Daw, Murray S.; Bauschlicher, Charles W.


    Ultra high temperature ceramics (UHTC) including ZrB2 and HfB2 are candidate materials for applications in extreme environments because of their high melting point, good mechanical properties and reasonable oxidation resistance. Unlike many ceramics, these materials have high thermal conductivity which can be advantageous, for example, to reduce thermal shock. Recently, we developed Tersoff style interatomic potentials for both ZrB2 and HfB2 appropriate for atomistic simulations. As an application, Green-Kubo molecular dynamics simulations were performed to evaluate the lattice thermal conductivity for single crystals of ZrB2 and HfB2. The atomic mass difference in these binary compounds leads to oscillations in the time correlation function of the heat current. Results at room temperature and at elevated temperatures will be reported.

  9. Experiences and Future Expectations towards Online Courses--An Empirical Study of the B2C-and B2B-Segments (United States)

    Krämer, Andreas; Böhrs, Sandra


    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…

  10. Lightweight MgB2 superconducting 10 MW wind generator (United States)

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


    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.

  11. 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


    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.

  12. 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


    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.

  13. Electronic structure and superconductivity of MgB2

    Indian Academy of Sciences (India)

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


    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.

  14. Thermodynamic and transport properties of superconducting Mg10B2. (United States)

    Finnemore, D K; Ostenson, J E; Bud'ko, S L; Lapertot, G; Canfield, P C


    Transport and thermodynamic properties of a sintered pellet of the newly discovered MgB2 superconductor have been measured to determine the characteristic critical magnetic fields and critical current densities. Both resistive transition and magnetization data give similar values of the upper critical field, Hc2, with magnetization data giving dHc2/dT = 0.44 T/K at the transition temperature of Tc = 40.2 K. Close to the transition temperature, magnetization curves are thermodynamically reversible, but at low temperatures the trapped flux can be on the order of 1 T. The value of dHc/dT at Tc is estimated to be about 12 mT/K, a value similar to classical superconductors like Sn. Hence, the Ginzburg-Landau parameter kappa approximately 26. Estimates of the critical supercurrent density, Jc, using hysteresis loops and the Bean model, give critical current densities on the order of 10(5) A/cm2. Hence the supercurrent coupling through the grain boundaries is comparable to intermetallics like Nb3Sn.

  15. Scheme to prepare the MgB2 superconducting multilayer films%MgB2超导多层膜的制备方案

    Institute of Scientific and Technical Information of China (English)

    罗子江; 杨健; 王继红



  16. 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


    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.

  17. 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)



    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.

  18. Thermal Vacuum Integrated System Test at B-2 (United States)

    Kudlac, Maureen T.; Weaver, Harold F.; Cmar, Mark D.


    The National Aeronautics and Space Administration (NASA) Glenn Research Center (GRC) Plum Brook Station (PBS) Space Propulsion Research Facility, commonly referred to as B-2, is NASA s third largest thermal vacuum facility. It is the largest designed to store and transfer large quantities of liquid hydrogen and liquid oxygen, and is perfectly suited to support developmental testing of chemical propulsion systems as well as fully integrated stages. The facility is also capable of providing thermal-vacuum simulation services to support testing of large lightweight structures, Cryogenic Fluid Management (CFM) systems, electric propulsion test programs, and other In-Space propulsion programs. A recently completed integrated system test demonstrated the refurbished thermal vacuum capabilities of the facility. The test used the modernized data acquisition and control system to monitor the facility during pump down of the vacuum chamber, operation of the liquid nitrogen heat sink (or cold wall) and the infrared lamp array. A vacuum level of 1.3x10(exp -4)Pa (1x10(exp -6)torr) was achieved. The heat sink provided a uniform temperature environment of approximately 77 K (140deg R) along the entire inner surface of the vacuum chamber. The recently rebuilt and modernized infrared lamp array produced a nominal heat flux of 1.4 kW/sq m at a chamber diameter of 6.7 m (22 ft) and along 11 m (36 ft) of the chamber s cylindrical vertical interior. With the lamp array and heat sink operating simultaneously, the thermal systems produced a heat flux pattern simulating radiation to space on one surface and solar exposure on the other surface. The data acquired matched pretest predictions and demonstrated system functionality.

  19. Thermal vacuum integrated system test at B-2 (United States)

    Kudlac, M. T.; Weaver, H. F.; Cmar, M. D.


    The National Aeronautics and Space Administration (NASA) Glenn Research Center (GRC) Plum Brook Station (PBS) Space Propulsion Research Facility, commonly referred to as B-2, is NASA's third largest thermal vacuum facility. It is the largest designed to store and transfer large quantities of liquid hydrogen and liquid oxygen, and is perfectly suited to support developmental testing of chemical propulsion systems as well as fully integrated stages. The facility is also capable of providing thermal-vacuum simulation services to support testing of large lightweight structures, Cryogenic Fluid Management (CFM) systems, electric propulsion test programs, and other In-Space propulsion programs. A recently completed integrated system test demonstrated the refurbished thermal vacuum capabilities of the facility. The test used the modernized data acquisition and control system to monitor the facility during pump down of the vacuum chamber, operation of the liquid nitrogen heat sink (or cold wall) and the infrared lamp array. A vacuum level of 1.3 × 10-4 Pa (1 × 10-6 torr) was achieved. The heat sink provided a uniform temperature environment of approximately 77 K (139°R) along the entire inner surface of the vacuum chamber. The recently rebuilt and modernized infrared lamp array produced a nominal heat flux of 1.4 kW/m2 at a chamber diameter of 6.7 m (22 ft) and along 11 m (36 ft) of the chamber's cylindrical vertical interior. With the lamp array and heat sink operating simultaneously, the thermal systems produced a heat flux pattern simulating radiation to space on one surface and solar exposure on the other surface. The data acquired matched pretest predictions and demonstrated system functionality.

  20. Beyond the exchange--the future of B2B. (United States)

    Wise, R; Morrison, D


    Using the Internet to facilitate business-to-business commerce promises many benefits, such as dramatic cost reductions and greater access to buyers and sellers. Yet little is known about how B2B e-commerce will evolve. The authors argue that changes in the financial services industry over the past two decades provide important clues. Exchanges, they say, are not the primary source of value in information-intensive markets; value tends to accumulate among a diverse group of specialists that focus on such tasks as packaging, standard setting, arbitrage, and information management. Because scale and liquidity are vitally important to efficient trading, today's exchanges will consolidate into a relatively small set of mega-exchanges. Originators will handle the origination and aggregation of complex transactions before sending them on to mega-exchanges for execution. E-speculators, seeking to capitalize on an abundance of market information, will tend to concentrate where relatively standardized products can be transferred easily among a large group of buyers. In many markets, a handful of independent solution providers with well-known brand names and solid reputations will thrive alongside mega-exchanges. Sell-side asset exchanges will create the networks and provide the tools to allow suppliers to trade orders among themselves, sometimes after initial transactions with customers are made on the mega-exchanges. For many companies, traditional skills in such areas as product development, manufacturing, and marketing may become relatively less important, while the ability to understand and capitalize on market dynamics may become considerably more important.

  1. Comparative immunohistochemical localisation of GABA(B1a), GABA(B1b) and GABA(B2) subunits in rat brain, spinal cord and dorsal root ganglion. (United States)

    Charles, K J; Evans, M L; Robbins, M J; Calver, A R; Leslie, R A; Pangalos, M N


    GABA(B) receptors are G-protein-coupled receptors mediating the slow onset and prolonged synaptic actions of GABA in the CNS. The recent cloning of two genes, GABA(B1) and GABA(B2), has revealed a novel requirement for GABA(B) receptor signalling. Studies have demonstrated that the two receptor subunits associate as a GABA(B1)/GABA(B2) heterodimer to form a functional GABA(B) receptor. In this study we have developed polyclonal antisera specific to two splice variants of the GABA(B1) subunit, GABA(B1a) and GABA(B1b), as well as an antiserum to the GABA(B2) subunit. Using affinity-purified antibodies derived from these antisera we have mapped out the distribution profile of each subunit in rat brain, spinal cord and dorsal root ganglion. In brain the highest areas of GABA(B1a), GABA(B1b) and GABA(B2) subunit expression were found in neocortex, hippocampus, thalamus, cerebellum and habenula. In spinal cord, GABA(B1) and GABA(B2) subunits were expressed in the superficial layers of the dorsal horn, as well as in motor neurones in the deeper layers of the ventral horn. GABA(B) receptor subunit immunoreactivity in dorsal root ganglion suggested that expression of GABA(B1b) was restricted to the large diameter neurones, in contrast to GABA(B1a) and GABA(B2) subunits which were expressed in both large and small diameter neurones. Although expression levels of GABA(B1) and GABA(B2) subunits varied we found no areas in which GABA(B1) was expressed in the absence of GABA(B2). This suggests that most, if not all, GABA(B1) immunoreactivity may represent functional GABA(B) receptors. Although our data are in general agreement with functional studies, some discrepancies in GABA(B1) subunit expression occurred with respect to other immunohistochemical studies. Overall our data suggest that GABA(B) receptors are widely expressed throughout the brain and spinal cord, and that GABA(B1a) and GABA(B1b) subunits can associate with GABA(B2) to form both pre- and post-synaptic receptors.

  2. Data of evolutionary structure change: 1VL8B-2UVDB [Confc[Archive

    Lifescience Database Archive (English)


  3. 17 CFR 240.13b2-1 - Falsification of accounting records. (United States)


    ... 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...

  4. 26 CFR 1.668(b)-2 - Illustration of the provisions of subpart D. (United States)


    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Illustration of the provisions of subpart D. 1.668(b)-2 Section 1.668(b)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... Taxable Years Beginning Before January 1, 1969 § 1.668(b)-2 Illustration of the provisions of subpart...

  5. Immunohistochemical study in dural arteriovenous fistula and possible role of ephrin-B2 for development of dural arteriovenous fistula

    Institute of Scientific and Technical Information of China (English)

    Wuttipong Tirakotai 王宝隆; BIAN Liu-guan 卞留贯; Helmut Bertalanffy; Siegfried Bien; Ulrich Sure


    Background Although there were several clinical and experimental studies discussing the pathogenesis of dural arteriovenous fistula (DAVF), the pathological process leading to intracranial DAVF so far remains unknown. In this study, we investigated the expression of vascular growth factors in order to elucidate the possible role of these factors for the development of DAVF and to study the biological activity of this uncommon lesion.Methods We examined the histological features, proliferative and angiogenic capacities of the tissue specimens obtained from 6 patients who underwent surgery at our institution. Immunohistochemical staining for vascular endothelial growth factor (VEGF), its receptors Flk-1 and Flt-1, ephrin-B2, MIB-1 and proliferating cell nuclear antigen (PCNA) was performed using standard immunohistochemical techniques. Results A positive immunostaining was found for all antibodies studied except MIB-1, whereas nuclear endothelial expression of PCNA was observed in only 3/6 cases. VEGF stained positive in all of the available specimens (6/6). Flk-1 showed a positive immunoreaction in only 2/6 cases and Flt-1 in 4/6 cases. Ephrin-B2 was expressed in the majority (5/6) of the cases.Conclusions These results support the hypothesis that DAVFs might be acquired dynamic vascular malformations with low biological activity. Vascular growth factors like VEGF and ephrin-B2 might play a pivotal role in the formation of DAVF.

  6. Thermoelastic properties of ScB2, TiB2, YB4 and HoB4: Experimental and theoretical studies

    DEFF Research Database (Denmark)

    Waśkowska, A.; Gerward, Leif; Staun Olsen, J.


    High-pressure X-ray diffraction in ScB2, TiB2, YB4 and HoB4 powders and single crystals has been studied using synchrotron radiation as well as conventional X-rays. The experimental results are supported by calculations using density functional theory. ScB2, YB4 and HoB4 are hard materials (bulk...... modulus 180–200 GPa), while TiB2 may be classified as superhard (bulk modulus about 260 GPa). We report here first experimental and theoretical determinations of the bulk modulus for HoB4 (195(5) and 198.2 GPa, respectively), and first experimental values of the bulk modulus for ScB2 (196(2) GPa) and YB4...

  7. LETTER TO THE EDITOR: Unique Fermi surfaces with quasi-one-dimensional character in CeRh3B2 and LaRh3B2 (United States)

    Okubo, T.; Yamada, M.; Thamizhavel, A.; Kirita, S.; Inada, Y.; Settai, R.; Harima, H.; Takegahara, K.; Galatanu, A.; Yamamoto, E.; Onuki, Y.


    We have carried out de Haas-van Alphen (dHvA) experiments on a ferromagnet CeRh3B2 with an extremely high Curie temperature T_{\\mathrm {C}} \\simeq 120 K and a non-4f reference compound LaRh3B2. The dHvA data of LaRh3B2 are well explained by the results of energy band calculations. The topology of the Fermi surfaces in CeRh3B2 is found to be very similar to that of LaRh3B2, possessing wavy but flat Fermi surfaces in the basal plane. Observation of a quasi-one-dimensional electronic state is the first such case in a rare earth compound.

  8. 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


    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.

  9. 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


    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.

  10. Characterization and Evaluation of TiB2-AlN Composites for Armor Applications (United States)


    titanium diboride (TiB2) and aluminum nitride (AlN) of varying compositions were consolidated by hot pressing. The compositions examined were 30-vol% TiB2...ceramic composite of titanium diboride (TiB2) and aluminum nitride (AlN) was chosen to be evaluated. TiB2 has been reported (3) to have high...showed some oxygen, which could be surface contamination , and sulfur impurities. 5 Figure 1. XRD spectrum of TiB2 powder. Figure 2

  11. ErbB2 signaling at the crossing between heart failure and cancer


    Vermeulen, Zarha; Segers, Vincent F.M.; De Keulenaer, Gilles W.


    The dual role of ErbB2 (or HER-2) in tumor growth and in physiological adaptive reactions of the heart positions ErbB2 at the intersection between cancer and chronic heart failure. Accordingly, ErbB2-targeted inhibitory therapy of cancer may lead to ventricular dysfunction, and activation of ErbB2 for heart failure therapy may induce malignancy. The molecular processes leading to the activation of ErbB2 in tumors and cardiac cells are, however, fundamentally different from each other. Thus, i...

  12. Generation of Pediatric Leukemia Xenograft Models in NSG-B2m Mice: Comparison with NOD/SCID Mice. (United States)

    Gopalakrishnapillai, Anilkumar; Kolb, E Anders; Dhanan, Priyanka; Bojja, Aruna Sri; Mason, Robert W; Corao, Diana; Barwe, Sonali P


    Generation of orthotopic xenograft mouse models of leukemia is important to understand the mechanisms of leukemogenesis, cancer progression, its cross talk with the bone marrow microenvironment, and for preclinical evaluation of drugs. In these models, following intravenous injection, leukemic cells home to the bone marrow and proliferate there before infiltrating other organs, such as spleen, liver, and the central nervous system. Moreover, such models have been shown to accurately recapitulate the human disease and correlate with patient response to therapy and prognosis. Thus, various immune-deficient mice strains have been used with or without recipient preconditioning to increase engraftment efficiency. Mice homozygous for the severe combined immune deficiency (SCID) mutation and with non-obese diabetic background (NOD/SCID) have been used in the majority of leukemia xenograft studies. Later, NOD/SCID mice deficient for interleukin 2 receptor gamma chain (IL2Rγ) gene called NSG mice became the model of choice for leukemia xenografts. However, engraftment of leukemia cells without irradiation preconditioning still remained a challenge. In this study, we used NSG mice with null alleles for major histocompatibility complex class I beta2-microglobulin (β2m) called NSG-B2m. This is a first report describing the 100% engraftment efficiency of pediatric leukemia cell lines and primary samples in NSG-B2m mice in the absence of host preconditioning by sublethal irradiation. We also show direct comparison of the engraftment efficiency and growth rate of pediatric acute leukemia cells in NSG-B2m and NOD/SCID mice, which showed 80-90% engraftment efficiency. Secondary and tertiary xenografts in NSG-B2m mice generated by injection of cells isolated from the spleens of leukemia-bearing mice also behaved similar to the primary patient sample. We have successfully engrafted 25 acute lymphoblastic leukemia (ALL) and 5 acute myeloid leukemia (AML) patient samples with

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

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


    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.

  14. Magnetic and Transport Studies in LaxGd1-xRh3B2 and CexGd1-xRh3B2 (United States)

    Vaidya, Ulhas; Dhar, S. K.; Thamizhavel, A.; Ramakrishnan, S.; Grover, A. K.


    The nonmagnetic rare earth ternary boride LaRh3B2, a hexagonal system of space group P6/mmm with CeCo3B2 type structure, is known to superconduct below Tc(0)˜ 2.7 K. When doped with Gd the Tc(0) reduces and no superconductivity is observed above 1.2 K with more than 15% (atomic) doping. The alloys, La0.8Gd0.2Rh3B2 and La0.6Gd0.4Rh3B2 show a jump at ˜ 70 K and rapid rise in magnetization below 10 K. However, no peaks are observed in at these temperatures in AC susceptibility which would have indicated magnetic ordering of the system. It is worth noting that GdRh3B2 orders ferromagnetically at ˜ 93 K. We shall present results of our investigations, above 2 K, in magnetic and transport properties of polycrystalline specimens LaxGd1-xRh3B2 (0 CeRh3B2 is a ferromagnet with Tc ˜ 115 K. The results of Gd doping in this reveal the survival of antiferromagnetic coupling between Ce and Gd spins.

  15. Microstructure and mechanical properties investigation of in situ TiB2 and ZrB2 reinforced Al-4Cu composites (United States)

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


    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.

  16. 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: [Institute of Medical Biology, Polish Academy of Sciences, Lodz (Poland); Department of Molecular and Medical Biophysics, Medical University of Lodz (Poland)


    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.

  17. EphB2 tyrosine kinase-dependent forward signaling in migration of neuronal progenitors that populate and form a distinct region of the dentate niche. (United States)

    Catchpole, Timothy; Henkemeyer, Mark


    The dentate gyrus (DG) is one of two areas in the mature brain where stem cells reside to continuously produce new neurons throughout adulthood. While much research has focused on the DG for its roles in adult neurogenesis, little is known regarding how this key region of the brain initially develops to form its distinct architecture. We show here that the murine EphB2 receptor tyrosine kinase is critical for embryonic/postnatal development of a specific region of the DG known as the lateral suprapyramidal blade (LSB). Intracellular truncation and point mutants demonstrate that EphB2 catalytic activity is essential for LSB formation. This is consistent with expression of EphB2 in nestin-positive neural progenitor cells that migrate medially from the lateral ventricle dentate notch neuroepithelium to populate the tertiary matrix and form the DG near the midline of the brain. Animals lacking ephrin-B1 recapitulate loss of the receptor and show that this molecule acts as the ligand to stimulate EphB2 forward signaling and direct migration of the neural progenitors into the dorsal compartment of the tertiary matrix and form the LSB. Immunoreactivity against the extracellular matrix protein Reelin in a region directly above the developing LSB is dramatically reduced when EphB2 forward signaling is disrupted. Together, these results indicate ephrin-B1 interacting with EphB2 controls the migration of dentate progenitor cells into the dorsal half of the developing DG, perhaps in part by affecting Reelin expression in a key compartment directly above the LSB.

  18. B2C电子商务市场的逆向物流分析%Analysis on Reverse Logistic in B2C Electronic Commerce Market

    Institute of Scientific and Technical Information of China (English)

    刘田; 牟援朝



  19. 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)



    @@ 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.

  20. Naked Polyamidoamine Polymers Intrinsically Inhibit Angiotensin II-Mediated EGFR and ErbB2 Transactivation in a Dendrimer Generation- and Surface Chemistry-Dependent Manner. (United States)

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


    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.

  1. The soluble extracellular domain of EphB4 (sEphB4) antagonizes EphB4-EphrinB2 interaction, modulates angiogenesis, and inhibits tumor growth


    Kertesz, Nathalie; Krasnoperov, Valery; Reddy, Ramachandra; Leshanski, Lucy; Kumar, S. Ram; Zozulya, Sergey; Gill, Parkash S.


    The receptor tyrosine kinase EphB4 and its ligand EphrinB2 play a crucial role in vascular development during embryogenesis. The soluble monomeric derivative of the extracellular domain of EphB4 (sEphB4) was designed as an antagonist of EphB4/EphrinB2 signaling. sEphB4 blocks activation of EphB4 and EphrinB2; suppresses endothelial cell migration, adhesion, and tube formation in vitro; and inhibits the angiogenic effects of various growth factors (VEGF and bFGF) in vivo. sEphB4 also inhibits ...

  2. Ephrin B2 is involved in Porphyromonas gingivalis infection-enhanced adhesion of THP-1 to human umbilical vein endothelial cells%肝配蛋白B2在牙龈卟啉单胞菌诱导单核细胞黏附人脐静脉内皮细胞中的作用

    Institute of Scientific and Technical Information of China (English)

    张彩霞; 宋洁; 徐杨; 吴娟; 孙卫斌; 李宽钰


    Objective To investigate the mechanisms of Porphyromonas gingivalis(Pg) infection-mediated enhancement of adhesion between monocytes THP-1 and human umbilical vein endothelial cells(HUVEC) by detecting the effect of erythropoietin producing hepatomocellular receptor interacting protein B2(Ephrin B2) and its receptors on the adhesion.Methods PgATCC33277 was cultured in an anaerobic jar,and THP-1 cells were infected with various concentrations of Pg at multiplicity of infection(MOI) of 1:100 for 8 and 24 h,respectively.The expression of Ephrin B2 receptor of THP-1 cells was detected.After removal of the free Pg,THP-1 cells were cocultured with HUVEC(overexpress of EphrinB2 or not) for 24 h to detect the expression of Ephrin B2 of HUVEC cells after additional cultivation for 23 h.Results The adhesion of THP-1 cells post infection by Pg to HUVEC was enhanced.The mRNA levels of Ephrin B2 receptors,including EphB3(5.169±0.152,P=0.005),EphB4(11.040± 1.195,P=0.001),and EphA4(4.976± 0.122,P=0.001) expressed by THP-1,and Ephrin B2(8.938±0.962,P=0.008) expressed by HUVEC were significantly elevated 24 h post infection of Pg.Over expression of Ephrin B2 in HUVEC promoted the adhesion of THP-1 to HUVEC.Conclusions Ephrin B2 and its receptors are involved in Pg infection mediated enhancement of the adhesion of THP-1 to HUVEC cells,suggesting that Ephrin B2 participates in the development of atherosclerosis.%目的 检测肝配蛋白B2 (erythropoietin producing hepatomocellular receptor interacting protein B2,Ephrin B2)及其受体在单核细胞THP-1黏附人脐静脉内皮细胞(human umbilical vein endothelial cell,HUVEC)中的作用,揭示牙龈卟啉单胞菌(Porphyromonas gingivalis,Pg)感染增强THP-1黏附HUVEC的分子机制.方法 应用厌氧罐培养Pg,以感染复数1∶100感染人单核细胞株THP-1,感染8和24 h后,收集部分样品分别用于检测THP-1细胞Ephrin B2及其受体表达水平的变化;其余样品与转染空载体或过表达Ephrin B2

  3. Secretion of SerpinB2 from endothelial cells activated with inflammatory stimuli. (United States)

    Boncela, Joanna; Przygodzka, Patrycja; Wyroba, Elzbieta; Papiewska-Pajak, Izabela; Cierniewski, Czeslaw S


    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 43kDa 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.

  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


    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. EphB1 and EphB2 intracellular domains regulate the formation of the corpus callosum and anterior commissure. (United States)

    Robichaux, Michael A; Chenaux, George; Ho, Hsin-Yi Henry; Soskis, Michael J; Greenberg, Michael E; Henkemeyer, Mark; Cowan, Christopher W


    The two cortical hemispheres of the mammalian forebrain are interconnected by major white matter tracts, including the corpus callosum (CC) and the posterior branch of the anterior commissure (ACp), that bridge the telencephalic midline. We show here that the intracellular signaling domains of the EphB1 and EphB2 receptors are critical for formation of both the ACp and CC. We observe partial and complete agenesis of the corpus callosum, as well as highly penetrant ACp misprojection phenotypes in truncated EphB1/2 mice that lack intracellular signaling domains. Consistent with the roles for these receptors in formation of the CC and ACp, we detect expression of these receptors in multiple brain regions associated with the formation of these forebrain structures. Taken together, our findings suggest that a combination of forward and reverse EphB1/2 receptor-mediated signaling contribute to ACp and CC axon guidance.

  6. Reserch and Progress in MgB2 Matrix Superconductive Material%MgB2基超导材料研究进展

    Institute of Scientific and Technical Information of China (English)

    黄勇; 刘心宇; 曾中明



  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


    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 (United States)

    Park, G. Barratt; Jiang, Jun; Saladrigas, Catherine A.; Field, Robert W.


    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. Development and Application of Interatomic Potentials for Ultra High Temperature Ceramics (UHTC): ZrB2 and HfB2 (United States)

    Lawson, John W.; Daw, Murray; Bauschlicher


    Ultra high temperature ceramics (UHTC) including ZrB2 and HfB2 are characterized by high melting point, good strength, and reasonable oxidation resistance. These materials are of interest for use as sharp leading edges for hypersonic vehicles among other applications. Progress in computational modeling of UHTCs has been limited in part due to the absence of suitable interatomic potentials. We present a Tersoff style parameterization of such potentials for ZrB2 and HfB2 appropriate for atomistic simulations. Parameters are fit to data generated from ab initio calculations. The accuracy of the potentials is assessed against further ab initio data. As a first non ]trivial application, molecular dynamics simulations are performed to evaluate the thermal conductivity of single crystals and the thermal resistance of high symmetry grain boundaries.

  10. Observation of b2 symmetry vibrational levels of the SO2 C̃ (1)B2 state: Vibrational level staggering, Coriolis interactions, and rotation-vibration constants. (United States)

    Park, G Barratt; Jiang, Jun; Saladrigas, Catherine A; Field, Robert W


    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.

  11. 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


    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.

  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


    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. Oxidation Resistance of ZrB2-SiC Multilayer Ceramics%ZrB2–SiC多层陶瓷的抗氧化性

    Institute of Scientific and Technical Information of China (English)

    左凤娟; 成来飞; 张立同


    ZrB2-SiC multilayer ceramic was prepared by a coneventional ceramic tape casting technology. The density was measured using the Archimede method. The microstructure of samples was observed by scanning electron microscopy. The oxidation resistance ofZrB2-SiC multilayer ceramics was also determined. The results indicate that for the product sintered at 1 950 ℃, the relative density is 99.7%. During the oxidation process of this material, the low melting phase is firstly volatilized, and then the oxidation layer is formed, which can diminish the further oxidation. The oxidation resistance of ZrB2-SiC multilayer ceramic was better than that of ZrB2-SiC monolithic ceramics.%用传统陶瓷的流延工艺制备ZrB2–SiC多层陶瓷。用Archimedes法测定ZrB2–SiC多层陶瓷的相对密度。用扫描电子显微镜观察其显微结构,并进行循环抗氧化性能评价。结果表明:ZrB2–SiC多层陶瓷在1 950℃烧结的致密度达到99.7%,材料的抗氧化过程主要可分为两个阶段:第一阶段低熔点相的挥发,出现质量损失;第二阶段氧化层的形成,降低进一步氧化速率。抗氧化性能较ZrB2–SiC复相陶瓷有很大提高。

  14. Advance in Research of TiB2 Materials%TiB2材料的研究现状

    Institute of Scientific and Technical Information of China (English)

    李苏; 李俊寿; 赵芳; 张颖


    TiB2材料作为一种新型先进材料,由于具有强度高、硬度高、耐磨损、耐腐蚀、熔点高、蒸气压低、导电性良好等优点而被广泛研究.介绍了TiB2材料的晶体结构与性质及其制备方法,包括直接合成法、碳热法、镁热法、溶胶-凝胶法、化学气相沉积法等,并分析总结了TiB2材料的致密化、涂层、复相陶瓷、微纳米结构等应用研究热点.其中,将两种或多种方法结合起来制备TiB2,已成为降低成本、减少污染、优化性能的重要途径.%As advanced materials, TiB2 materials have been widely studied because of their good properties,such as high strength,high hardness, wear resistance,corrosion resistance,high melting point,low vapor pressure,good electrical conductivity and so on. The crystal structural properties and preparation methods of TiB2 materials are introduced, such as direct synthesis, carbon thermal method, magnesium thermal method, sol-gel method, chemical vapor deposition method and so oa The reviews on densification, coating,multiphase ceramics and micro-nano structure of TiB2 materials are given as the research hotspots. Combining with two or more methods to synthesize TiB2 has been an important way of cost down, pollution reduction and performance optimization

  15. Research Progress of Doping in MgB2 Superconducting Material%MgB2超导材料掺杂研究进展

    Institute of Scientific and Technical Information of China (English)

    付尧; 张松; 吴燕平; 邓朝勇



  16. Research on B2C Buying Online Mode%基于B2C的网络团购模式研究

    Institute of Scientific and Technical Information of China (English)



    Purchasing online trade is seen more and more frequently in our country since the beginning of 21st century, and a large quantity of B2C websites for purchasing online have appeared. The factors influencing purchasing online are bargaining space, buyer expectation, competitive situation and so on. All of these factors play a decisive role for B2C purchasing online mode. Summing up the development of various purchasing online modes, eight B2C purchasing online modes can be divided from the three latitudes of sponsors, diversity of products and the number of buyers.%我国从21世纪以来网络团购交易越来越频繁,出现了大批的B2C网络团购网站。影响网络团购的因素有议价空间、买方预期、竞争状况等,这些因素对于B2C网络团购模式都有决定性的作用,总结多种团购模式发现,较为稳定的八种B2C网络团购模式都可从发起者、产品的多样性及卖家数量三个维度来进行划分。

  17. Study of TiB2 Ceramics via SHS/PHIP%SHS/PHIP法合成TiB2陶瓷的研究

    Institute of Scientific and Technical Information of China (English)

    徐强; 张幸红; 曲伟; 韩杰才



  18. Microhardness and microstructure evolution of TiB2 reinforced Inconel 625/TiB2 composite produced by selective laser melting (United States)

    Zhang, Baicheng; Bi, Guijun; Nai, Sharon; Sun, Chen-nan; Wei, Jun


    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).

  19. Lattice Thermal Conductivity of Ultra High Temperature Ceramics (UHTC) ZrB2 and HfB2 from Atomistic Simulations (United States)

    Lawson, John W.; Daw, Murray S.; Bauschlicher, Charles W.


    Ultra high temperature ceramics (UHTC) including ZrB2 and HfB2 have a number of properties that make them attractive for applications in extreme environments. One such property is their high thermal conductivity. Computational modeling of these materials will facilitate understanding of fundamental mechanisms, elucidate structure-property relationships, and ultimately accelerate the materials design cycle. Progress in computational modeling of UHTCs however has been limited in part due to the absence of suitable interatomic potentials. Recently, we developed Tersoff style parameterizations of such potentials for both ZrB2 and HfB2 appropriate for atomistic simulations. As an application, Green-Kubo molecular dynamics simulations were performed to evaluate the lattice thermal conductivity for single crystals of ZrB2 and HfB2. The atomic mass difference in these binary compounds leads to oscillations in the time correlation function of the heat current, in contrast to the more typical monotonic decay seen in monoatomic materials such as Silicon, for example. Results at room temperature and at elevated temperatures will be reported.

  20. Critical current density and flux pinning in Zr0.96V0.04B2 superconductor with AlB2 structure (United States)

    Jung, Soon-Gil; Vanacken, J.; Moshchalkov, V. V.; Renosto, S. T.; dos Santos, C. A. M.; Machado, A. J. S.; Fisk, Z.; Albino Aguiar, J.


    We have investigated the critical current density (Jc) and the flux pinning behavior in Zr0.96V0.04B2 superconductor with an AlB2 structure. V substitutions in Zr sites of non-superconducting ZrB2 system lead to superconductivity, and the 4% V-substituted Zr0.96V0.04B2 compounds show the highest superconducting transition temperature (Tc) of ˜8.7 K. The magnetic hysteresis (M-H) loops for the Zr0.96V0.04B2 demonstrate type-II superconducting behavior in a broad temperature range, and the Jc is estimated from the M-H loops using the Bean model. The analysis of the double-logarithmic Jc(H) plots indicates the dominance of collective pinning in Zr0.96V0.04B2, and that Jc(H) and magnetic field dependences of the flux pinning force density (Fp) are well fitted by the double exponential model which takes into account the existence of two superconducting gaps.

  1. Fast creation of dense MgB2 phase in wires made by IMD process (United States)

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


    Single-core MgB2 wires have been made by internal magnesium diffusion (IMD) into boron process. Heat treatments were performed at variable periods (4-90 min) for two adjusted temperatures 635 °C and 650 °C, with an overshoot of ≈20 °C after 5 min. Critical currents of differently treated MgB2/Ti/GlidCop wires have been measured and related with the MgB2 layers. The fast creation MgB2 compound has been observed after 8 min annealing at both temperatures and showing the critical current maxima. The less uniform MgB2 containing cracks was created for longer annealing periods (≥10 min), which resulted in lowered critical currents and worsened thermal stability. The fast creation of dense MgB2 allows it to utilize a continual and short heat treatment process for high current density wires made by IMD.

  2. Do self-service technologies affect interfirm relationships? A B2B perspective


    Raechel Johns


    While considerable literature examines business-to business (B2B) relationships, the impact of technology on these relationships has lacked attention. IT has impacted the way businesses operate in a B2B context as well as influencing services by altering the way services are delivered. To understand the way in which Internet technology has impacted these B2B services, it is essential to examine its impact not only on business processes but on business relationships too. One technology, enable...

  3. ZrB2-TiB2 composite coating on surface of copper electrode by electrospark deposition%铜电极表面电火花沉积ZrB2-TiB2复相涂层

    Institute of Scientific and Technical Information of China (English)

    杨李安卓; 董仕节; 罗平; 孙世烜; 杨巍; 刘琪


    采用粉末冶金法制备ZrB2-TiB2复相材料熔敷棒,并通过电火花沉积工艺在铜电极表面制备ZrB2-TiB2复相涂层.通过扫描电镜结合能谱分析研究了涂层的显微结构和元素分布,利用X射线衍射和显微硬度测试对涂层的物相组成与显微硬度进行检测.结果表明:直接熔敷ZrB2-TiB2复相涂层致密性较差,且存在较多裂纹,与基体有明显分层,涂层物相为Cu、ZrB2和TiB2;在预沉积Ni层(Ni层)上后沉积ZrB2-TiB2,所得的多层涂层具有较好的致密性,且涂层与基体间无分层;中间层有Ti、Zr、Cu元素的扩散,说明涂层与基体为冶金结合;ZrB2-TiB2复相涂层硬度为900 HV0.05稍高于多层涂层硬度(800 HV0.05).

  4. A role of nesfatin-1/NucB2 in dehydration-induced anorexia. (United States)

    Yoshimura, Mitsuhiro; Matsuura, Takanori; Ohkubo, Junichi; Maruyama, Takashi; Ishikura, Toru; Hashimoto, Hirofumi; Kakuma, Tetsuya; Mori, Masatomo; Ueta, Yoichi


    Nesfatin-1/NucB2, an anorexigenic molecule, is expressed mainly in the hypothalamus, particularly in the supraoptic nucleus (SON) and the paraventricular nucleus (PVN). Nesfatin-1/NucB2 is also expressed in the subfornical organ (SFO). Because the SON and PVN are involved in body fluid regulation, nesfatin-1/NucB2 may be involved in dehydration-induced anorexia. To clarify the effects of endogenous nesfatin-1/NucB2, we studied changes in nesfatin-1/NucB2 mRNA levels in the SFO, SON, and PVN in adult male Wistar rats after exposure to osmotic stimuli by using in situ hybridization histochemistry. Significant increases in nesfatin-1/NucB2 mRNA levels, ∼2- to 3-fold compared with control, were observed in the SFO, SON, and PVN following water deprivation for 48 h, consumption of 2% NaCl hypertonic saline in drinking water for 5 days, and polyethylene glycol-induced hypovolemia. In addition, nesfatin-1/NucB2 expression was increased in response to water deprivation in a time-dependent manner. These changes in nesfatin-1/NucB2 mRNA expression were positively correlated with plasma sodium concentration, plasma osmolality, and total protein levels in all of the examined nuclei. Immunohistochemistry for nesfatin-1/NucB2 revealed that nesfatin-1/NucB2 protein levels were also increased after 48 h of dehydration and attenuated by 24 h of rehydration. Moreover, intracerebroventricular administration of nesfatin-1/NucB2-neutralizing antibody after 48 h of water deprivation resulted in a significant increase in food intake compared with administration of vehicle alone. These results suggested that nesfatin-1/NucB2 is a crucial peptide in dehydration-induced anorexia.

  5. Anomalous magnetism of CeRh3B2 under pressure (United States)

    Shaheen, S. A.; Schilling, J. S.; Klavins, P.; Vining, C. B.; Shelton, R. N.

    Whereas CeRh3B2 possesses the highest magnetic ordering temperature (T sub c approx. = 115K) of any Ce-compound with nonmagnetic constituents, LaRh3B2 becomes superconducting below 2.5K. Recent magnetization measurements under pressure as well as lattice parameter and specific heat studies shed light on the nature of the anomalous magnetic state in CeRh3B2.

  6. B2B marketingová komunikace společnosti John Deere



    The aim of this master's thesis is to evaluate the implementation of the B2B marketing strategy of John Deere on a specific example. The theoretical part of the thesis focuses on defining the basics of modern marketing communications. Next it deals with defining the concept of B2B marketing and related strategies. The practical part focuses on the characterisation of the agricultural machinery industry and the slovak agricultural sector. Further it includes the introduction of other B2B marke...

  7. Delivery of platinum(IV) drug to subcutaneous tumor and lung metastasis using bradykinin-potentiating peptide-decorated chitosan nanoparticles. (United States)

    Wang, Xin; Yang, Chenchen; Zhang, Yajun; Zhen, Xu; Wu, Wei; Jiang, Xiqun


    Selectively activating tumor vessels to increase drug delivery and reduce interstitial fluid pressure of tumors is actively pursued. Here we developed a vasoactive peptide-decorated chitosan nanoparticles for enhancing drug accumulation and penetration in subcutaneous tumor and lung metastasis. The vasoactive peptide used here is bradykinin-potentiating peptide (BPP) containing 9 amino acid residues and the drug is bioreductively sensitive platinum(IV) compound which becomes cisplatin in intracellular reductive environments. Both peptide and drug are covalently linked with chitosan nanoparticles with a diameter of 120 nm. We demonstrate that BPP-decorated chitosan nanoparticles increase the tumorous vascular permeability and reduce the interstitial fluid pressure of tumor simultaneously, both of which improve the penetration of nanoparticles in tumor tissues. The in vivo biodistribution and tumor inhibition examinations demonstrate that the BPP-decorated nanoparticle formulation has more superior efficacy in enhancing drug accumulation in tumor, restraining tumor growth and prolonging the lifetime of tumor-bearing mice than free drug and non-decorated nanoparticle formulation. Meanwhile, the drug accumulation in the lung with metastasis reaches 17% and 20% injected dose per gram of lung for the chitosan nanoparticles without and with BPP decoration, respectively, which is 10-fold larger than that of free cisplatin. The examination of lung metastasis inhibition further indicates that BPP-decorated chitosan nanoparticle formulations can more effectively inhibit lung metastasis.

  8. L-type calcium channel gating is modulated by bradykinin with a PKC-dependent mechanism in NG108-15 cells. (United States)

    Toselli, Mauro; Taglietti, Vanni


    Bradykinin (BK) excites dorsal root ganglion cells, leading to the sensation of pain. The actions of BK are thought to be mediated by heterotrimeric G protein-regulated pathways. Indeed there is strong evidence that in different cell types BK is involved in phosphoinositide breakdown following activation of G(q/11). In the present study we show that the Ca(2+) current flowing through L-type voltage-gated Ca(2+) channels in NG108-15 cells (differentiated in vitro to acquire a neuronal phenotype), measured using the whole-cell patch clamp configuration, is reversibly inhibited by BK in a voltage-independent fashion, suggesting a cascade process where a second messenger system is involved. This inhibitory action of BK is mimicked by the application of 1,2-oleoyl-acetyl glycerol (OAG), an analog of diacylglycerol that activates PKC. Interestingly, OAG occluded the effects of BK and both effects were blocked by selective PKC inhibitors. The down modulation of single L-type Ca(2+) channels by BK and OAG was also investigated in cell-attached patches. Our results indicate that the inhibitory action of BK involves activation of PKC and mainly shows up in a significant reduction of the probability of channel opening, caused by an increase and clustering of null sweeps in response to BK.

  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


    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. MgB2材料在超导科学中的研究

    Institute of Scientific and Technical Information of China (English)




  11. Isotope Effect on Electron-Phonon Coupling in Multiband Superconductor MgB2 (United States)

    Mou, Daixiang; Taufour, Valentin; Wu, Yun; Huang, Lunan; Bud'Ko, Serguei; Canfield, Paul; Kaminski, Adam

    We systematically investigate the isotope effect of electron-phonon coupling in multi-band superconductor MgB2 by laser based Angle Resolved Photoemission Spectroscopy. The kink structure around 70 meV on two σ bands, which is caused by electron coupling to E2 g phonon mode, is shifted to higher binding energy in Mg10B2 than that in Mg11B2. The measured shifting energy of 3.5 meV is consistent with theoretical calculation based on harmonic phonon in MgB2. Our temperature dependent measurement also indicates the isotope effect of kink structure is not dependent on superconducting transition.

  12. Al-doped MgB2 materials studied using electron paramagnetic resonance and Raman spectroscopy (United States)

    Bateni, Ali; Erdem, Emre; Repp, Sergej; Weber, Stefan; Somer, Mehmet


    Undoped and aluminum (Al) doped magnesium diboride (MgB2) samples were synthesized using a high-temperature solid-state synthesis method. The microscopic defect structures of Al-doped MgB2 samples were systematically investigated using X-ray powder diffraction, Raman spectroscopy, and electron paramagnetic resonance. It was found that Mg-vacancies are responsible for defect-induced peculiarities in MgB2. Above a certain level of Al doping, enhanced conductive properties of MgB2 disappear due to filling of vacancies or trapping of Al in Mg-related vacancy sites.

  13. Supercondcuting properties in MgB2/Fe wires prepared by PIT method

    Institute of Scientific and Technical Information of China (English)

    YAN Guo; FENG Yong; FU Baoquan; LIU Chunfang; JI Ping; ZHANG Pingxiang; ZHOU Lian


    The MgB2 formation was analyzed physically and chemically and the MgB2/Fe wires were fabricated by powder in tube (PIT) technology. The microstructureof MgB2 in wires was studied by the scanning electrical microscope (SEM), whichshows a good connection of grains and the size of MgB2 grain is 1-3μm. The results of Jc measured by the standard four probes method show that Jc value reaches 6.1×104 A/cm2 at 20 K in self field.

  14. MgB2 superconducting whiskers synthesized by using the hybrid physical-chemical vapor deposition. (United States)

    Wang, Yazhou; Zhuang, Chenggang; Gao, Jingyun; Shan, Xudong; Zhang, Jingmin; Liao, Zhimin; Xu, Hongjun; Yu, Dapeng; Feng, Qingrong


    In this work, MgB(2) whiskers were fabricated on a copper substrate by using the hybrid physical-chemical vapor deposition, which was one of the most effective ways to make high quality pure MgB(2) films, with the possible growth mechanism discussed. The whiskers are hexagonal and conelike and grow along the [0001] direction with a single-crystal structure. The onset transition temperature is approximately 39 K, which is among the best in the published nanostructure MgB(2) papers. Fabrication of nanoscale MgB(2) whiskers provides the fundamental understanding of the effect of dimensionality and size on superconductivity.

  15. Superconducting MgB2 flowers: growth mechanism and their superconducting properties (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


    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.

  16. Electrochemical Oxidation of Paracetamol Mediated by MgB2 Microparticles Modified Glassy Carbon Electrode


    Mohammed Zidan; Tan Wee Tee; A. Halim Abdullah; Zulkarnain Zainal; Goh Joo Kheng


    A MgB2 microparticles modified glassy carbon electrode (MgB2/GCE) was fabricated by adhering microparticles of MgB2 onto the electrode surface of GCE. It was used as a working electrode for the detection of paracetamol in 0.1 M KH2PO4 aqueous solution during cyclic voltammetry. Use of the MgB2/GCE the oxidation process of paracetamol with a current enhancement significantly by about 2.1 times. The detection limit of this modified electrode was found to be 30 μM. The sensitivity under conditio...

  17. Inhibition of ErbB-2 induces TFF3 downregulation in breast cancer cell lines. (United States)

    Yue, Lu; Xiang, Jinyu; Shen, Zan; Wang, Zhihao; Yao, Yasai; Zhou, Quan; Ding, Aiping; Qiu, Wensheng


    ErbB-2 gene plays an important role in carcinoma formation whose overexpression was observed in many types of tumors, including breast cancer. Dysregulation of Trefoil factor 3 (TFF3), which is thought to function in the development and progression of breast cancer, was found to be upregulated in ErbB2-overexpressing breast cancers and cells. However, a putative interaction between ErbB-2 and TFF3 in breast cancer remains unknown. To determine whether TFF3 has an important role in breast tumor, its levels were measured by immunohistochemistry in 130 cases of breast infiltrating duct carcinoma and 30 cases of normal breast tissue with a specific monoclonal antibody raised against human TFF3. Patients who were positive for ErbB-2 also had high expression levels of TFF3 (p TFF3 by real-time polymerase chain reaction and Western blotting, respectively. Compared with the control groups, ErbB-2 mRNA expression was decreased in the Lenti-ShERBB2 infection group, and Western blotting indicated a concordant ErbB-2 protein reduction. On the other hand, TFF3 expression at both mRNA and protein levels was significantly downregulated by ErbB-2 silencing in SK-BR-3. These findings are a proof of the foundation for a certain relationships of ErbB-2 and TFF3, which may serve as novel therapeutic markers of ErbB2-overexpressing breast cancers in the future.

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

    Directory of Open Access Journals (Sweden)

    Ivan Ćavar


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

  19. Effects of ZrB2 on substructure and wear properties of laser melted in situ ZrB2p/6061Al composites (United States)

    Zeng, Yida; Chao, Yuhjin; Luo, Zhen; Cai, Yangchuan; Huang, Yongxian


    Aluminum matrix composites reinforced by in situ ZrB2 particles were successfully fabricated from an Al-KBF4-K2ZrF6 system via a direct melt reaction. A laser surface melting strategy is used to improve the surface strength of the in situ ZrB2p/6061Al composite, which includes a series of laser-melted composites with different laser power processed by a 2 kW YAG laser generator. XRD and EDS results demonstrated the existence of ZrB2 nanoparticles in the composite. After laser melting, the penetration depth of the molten pool increases with increasing power density. OM and SEM analysis indicate that the laser melting process yields narrower cellular spacing of the matrix and partly disperses the ZrB2 particle clusters. Compared with laser-melted matrix alloys, the crystal orientations near the melted layers edge of the composite are almost random due to heterogeneous nucleation in the melt and the pinning effect of laser-dispersed ZrB2 nanoparticles at the solidification front. Wear test results show that the laser melted layer performs better at wear resistance than both the substrate and the matrix AA6061 by measuring wear mass loss. Compared with composite samples prepared without laser melting, the wear mass loss of the laser melted composites decreased from 61 to 56 mg under a load of 98 N for 60 min.

  20. In situ epitaxial MgB2 thin films for superconducting electronics. (United States)

    Zeng, Xianghui; Pogrebnyakov, Alexej V; Kotcharov, Armen; Jones, James E; Xi, X X; Lysczek, Eric M; Redwing, Joan M; Xu, Shengyong; Li, Qi; Lettieri, James; Schlom, Darrell G; Tian, Wei; Pan, Xiaoqing; Liu, Zi-Kui


    The newly discovered 39-K superconductor MgB2 holds great promise for superconducting electronics. Like the conventional superconductor Nb, MgB2 is a phonon-mediated superconductor, with a relatively long coherence length. These properties make the prospect of fabricating reproducible uniform Josephson junctions, the fundamental element of superconducting circuits, much more favourable for MgB2 than for high-temperature superconductors. The higher transition temperature and larger energy gap of MgB2 promise higher operating temperatures and potentially higher speeds than Nb-based integrated circuits. However, success in MgB2 Josephson junctions has been limited because of the lack of an adequate thin-film technology. Because a superconducting integrated circuit uses a multilayer of superconducting, insulating and resistive films, an in situ process in which MgB2 is formed directly on the substrate is desirable. Here we show that this can be achieved by hybrid physical-chemical vapour deposition. The epitaxially grown MgB2 films show a high transition temperature and low resistivity, comparable to the best bulk samples, and their surfaces are smooth. This advance removes a major barrier for superconducting electronics using MgB2.

  1. Combustion Synthesis and Densification of NiAl/TiB2 Composites

    Institute of Scientific and Technical Information of China (English)


    A suitable combustion synthesis and densification process was designed to fabricate dense NiAl/TiB2 composites from Ni-Al-Ti-B system. Combustion synthesis processing and microstructure characteristics of products were studied in detail.The results show that the amount of TiB2 ceramics has a great influence on the combustion synthesis processing and microstructure; with the increase of the amount of TiB2 ceramics, the combustion temperature and combustion velocity increase rapidly.The volume of synthesized products and the grain size of ceramics particle size are also affected by the amount of TiB2 ceramics.TiB2 ceramics fiber can be produced in this synthesis system.The dense NiAl/TiB2 composites with residual porosity of no more than 1% are fabricated by the combustion synthesis and hot pressing,the mechanical properties of the dense NiAl/TiB2 composites increase with increase of the amount of TiB2 ceramics.

  2. 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


    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.

  3. 26 CFR 1.6031(b)-2T - REMIC reporting requirements (temporary). [Reserved (United States)


    ... 26 Internal Revenue 13 2010-04-01 2010-04-01 false REMIC reporting requirements (temporary). 1.6031(b)-2T Section 1.6031(b)-2T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... requirements (temporary)....

  4. Magnetism in the system Ce1-xLaxRh3B2 (abstract) (United States)

    Malik, S. K.; Umarji, A. M.; Shenoy, G. K.; Aldred, T. A.; Niarchos, D. G.


    The RRh3B2 (R=La to Gd) compounds form in the hexagonal CeCo3B2-type structure. The La containing compound in this series has been reported to be a superconductor while CeRh3B2 orders magnetically with Ce being in a nearly 3+ state. The magnetic ordering in CeRh3B2 is presumed to arise from the hybridization of nearly localized 4f electrons of Ce with sp conduction electrons or the 4d band of Rh or from the hybridization of the two. We have examined the magnetic behavior of the system Ce1-xLaxRh3B2 (x=0.0, 0.2, 0.4, 0.6, and 0.8). All these compounds (except LaRh3B2) also order magnetically. The Curie temperature decreases from about 115 K for pure Ce compound to 2.3 K for Ce0.2La0.8Rh3B2. The magnetic moments per formula unit remains nearly constant for 0B2 for x ranging from 0.0 to 0.8. The La-rich side is being investigated for the occurrence of superconductivity. Details will be published elsewhere.

  5. 26 CFR 1.415(b)-2 - Multiple annuity starting dates. [Reserved (United States)


    ... 26 Internal Revenue 5 2010-04-01 2010-04-01 false Multiple annuity starting dates. 1.415(b)-2...) INCOME TAX (CONTINUED) INCOME TAXES Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.415(b)-2 Multiple annuity starting dates....

  6. Preparation and characterization of Sc doped MgB2 wires

    DEFF Research Database (Denmark)

    Grivel, Jean-Claude; Burdusel, M.


    The in-situ technique was used to manufacture scandium (Sc) doped MgB2 wires in a composite Cu–Nb sheath. After reaction at 700 °C, at most 1 at.% Mg was replaced by Sc in the MgB2 phase, without significant influence on its superconducting transition temperature. For higher Sc concentrations...

  7. A Decompositional Approach to Executing Quality Data Model Algorithms on the i2b2 Platform (United States)

    Mo, Huan; Jiang, Guoqian; Pacheco, Jennifer A.; Kiefer, Richard; Rasmussen, Luke V.; Pathak, Jyotishman; Denny, Joshua C.; Thompson, William K.


    The Quality Data Model (QDM) is an established standard for representing electronic clinical quality measures on electronic health record (EHR) repositories. The Informatics for Integrated Biology and the Bedside (i2b2) is a widely used platform for implementing clinical data repositories. However, translation from QDM to i2b2 is challenging, since QDM allows for complex queries beyond the capability of single i2b2 messages. We have developed an approach to decompose complex QDM algorithms into workflows of single i2b2 messages, and execute them on the KNIME data analytics platform. Each workflow operation module is composed of parameter lists, a template for the i2b2 message, an mechanism to create parameter updates, and a web service call to i2b2. The communication between workflow modules relies on passing keys ofi2b2 result sets. As a demonstration of validity, we describe the implementation and execution of a type 2 diabetes mellitus phenotype algorithm against an i2b2 data repository. PMID:27570665

  8. 17 CFR 270.24b-2 - Filing copies of sales literature. (United States)


    ... 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...

  9. Occurrence of Furnonisins B2 and B4 in Retail Raisins

    DEFF Research Database (Denmark)

    Knudsen, Peter Boldsen; Mogensen, Jesper Mølgaard; Larsen, Thomas Ostenfeld;


    -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...

  10. Antibacterial Peptide CecropinB2 Production via Various Host and Construct Systems

    Directory of Open Access Journals (Sweden)

    Wei-Shiang Lai


    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.

  11. 新型金属间化合物MgB2超导材料%Novel Intermetallic Compound MgB2 Superconductor

    Institute of Scientific and Technical Information of China (English)




  12. B2B电子集市重构中国流通经济%Reconstruction of China's Retail Industry through B2B Marketplace

    Institute of Scientific and Technical Information of China (English)



    @@ 自2000年4月美国NASDAQ股市狂跌以来,网络股票一直阴雨绵绵.很多DOTCOM公司 将会长期处于高危险的ILMI运行模式中(投资、烧钱、再投资,Invest,Lose Mo ney,Invest).曾几何时,网络股被炒得发烫.今天,从Boo.com公司的破产,I CP、B2C、B2B公司们的纷纷陨落,到B2C的业界翘楚Amazon.com遭到资本市场的棒 喝,曾经牛气冲天的Tom.com网站不得不裁掉近1/4的员工.真是此一时,彼一时 也.

  13. The dual targeting of EGFR and ErbB2 with the inhibitor Lapatinib corrects high glucose-induced apoptosis and vascular dysfunction by opposing multiple diabetes-induced signaling changes. (United States)

    Benter, Ibrahim F; Sarkhou, Fatima; Al-Khaldi, Abeer T; Chandrasekhar, Bindu; Attur, Sreeja; Dhaunsi, Gursev S; Yousif, Mariam H M; Akhtar, Saghir


    The epidermal growth factor receptors, EGFR and EGFR2 (ErbB2), appear important mediators of diabetes-induced vascular dysfunction. We investigated whether targeted dual inhibition of EGFR and ErbB2 with Lapatinib would be effective in treating diabetes-induced vascular dysfunction in a rat model of type 1 diabetes. In streptozotocin-induced diabetes, chronic 4-week oral or acute, ex vivo, administration of Lapatinib prevented the development of vascular dysfunction as indicated by the attenuation of the hyper-reactivity of the diabetic mesenteric vascular bed (MVB) to norephinephrine without correcting hyperglycemia. Chronic in vivo or acute ex vivo Lapatinib treatment also significantly attenuated diabetes-induced increases in phosphorylation of EGFR, ErbB2, ERK1/2, AKT, ROCK2 and IkB-alpha as well as normalized the reduced levels of phosphorylated FOXO3A, and eNOS (Ser1177) in the diabetic MVB. Similar results were observed in vascular smooth muscle cells (VSMCs) cultured in high glucose (25 mM) treated with Lapatinib or small interfering RNA (siRNA) targeting the ErbB2 receptor. Lapatinib also prevented high glucose-induced apoptosis in VSMC. Thus, Lapatinib corrects hyperglycemia-induced apoptosis and vascular dysfunction with concomitant reversal of diabetes or high glucose-induced signaling changes in EGFR/ErbB2 and downstream signaling pathways implying that targeted dual inhibition of EGFR/ErbB2 might be an effective vasculoprotective treatment strategy in diabetic patients.

  14. A New Method for Preparing Superconducting MgB2 Films from Diborane

    Institute of Scientific and Technical Information of China (English)

    王殿生; 傅兴华; 张正平; 杨健


    We report on a new preparation method for magnesium diboride (MgB2) films by chemical vapour deposition(CVD) from diborane (B2H6). It is a two-step ex situ approach, with the precursor boron films grown by CVD from B2H6 at 460°C, followed by a post-annealing process in magnesium (Mg) vapour at 830°C. The prepared MgB2 thin films on Al2O3 polycrystalline substrates have an onset transition temperature of 35K and a zeroresistance temperature of about 24K. Well-crystallized MgB2 grains have clearly been observed in the SEM images and confirmed by x-ray diffraction analysis. The advantages of the proposed method are the feasibility to prepare large-area superconducting films and the compatibility with semiconductor technology.

  15. Reactivity of carbides in synthesis of MgB 2 bulks (United States)

    Yamamoto, Akiyasu; Shimoyama, Jun-ichi; Ueda, Shinya; Horii, Shigeru; Kishio, Kohji


    The reactivity of various carbides (B4C, Al4C3, SiC, TiC, ZrC, NbC, Mo2C, HfC and WC) with magnesium and boron in synthesis of MgB2 was systematically studied. Decreases in the a-axis length and transition temperature were observed in all the carbide doped MgB2 bulks, reflecting a certain amount of carbon substituted for boron site in MgB2. The reactivity of each carbide estimated by the carbon content in MgB2 was found to be different depending on the chemical stability. Our results suggest that carbon content in MgB2 lattice can be controlled to its optimal doping level by adjusting synthesis conditions and selection of doping reagents.

  16. 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


    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.

  17. 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


    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.

  18. Study on the Transport Properties of Superconductor MgB2%MgB2超导体输运特性的研究

    Institute of Scientific and Technical Information of China (English)

    王洪涛; 郑素燕



  19. 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)




  20. Treatment of HAE Attacks in the Icatibant Outcome Survey

    DEFF Research Database (Denmark)

    Hernández Fernandez de Rojas, Dolores; Ibañez, Ethel; Longhurst, Hilary;


    BACKGROUND: Icatibant, a selective bradykinin B2 receptor antagonist for the treatment of acute hereditary angio-oedema (HAE) attacks in adults, can be administered by health care professionals (HCPs) or self-administered. This analysis compared characteristics and outcomes of acute HAE attacks t...

  1. Analysis of characteristics associated with reinjection of icatibant

    DEFF Research Database (Denmark)

    Longhurst, Hilary J; Aberer, Werner; Bouillet, Laurence


    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...

  2. Acetylcholine and bradykinin enhance hypotension and affect the function of remodeled conduit arteries in SHR and SHR treated with nitric oxide donors

    Directory of Open Access Journals (Sweden)

    Gerová M.


    Full Text Available Discrepancy was found between enhanced hypotension and attenuated relaxation of conduit arteries in response to acetylcholine (ACh and bradykinin (BK in nitric oxide (NO-deficient hypertension. The question is whether a similar phenomenon occurs in spontaneously hypertensive rats (SHR with a different pathogenesis. Wistar rats, SHR, and SHR treated with NO donors [molsidomine (50 mg/kg or pentaerythritol tetranitrate (100 mg/kg, twice a day, by gavage] were studied. After 6 weeks of treatment systolic blood pressure (BP was increased significantly in experimental groups. Under anesthesia, the carotid artery was cannulated for BP recording and the jugular vein for drug administration. The iliac artery was used for in vitro studies and determination of geometry. Compared to control, SHR showed a significantly enhanced (P < 0.01 hypotensive response to ACh (1 and 10 µg, 87.9 ± 6.9 and 108.1 ± 5.1 vs 35.9 ± 4.7 and 64.0 ± 3.3 mmHg, and BK (100 µg, 106.7 ± 8.3 vs 53.3 ± 5.2 mmHg. SHR receiving NO donors yielded similar results. In contrast, maximum relaxation of the iliac artery in response to ACh was attenuated in SHR (12.1 ± 3.6 vs 74.2 ± 8.6% in controls, P < 0.01. Iliac artery inner diameter also increased (680 ± 46 vs 828 ± 28 µm in controls, P < 0.01. Wall thickness, wall cross-section area, wall thickness/inner diameter ratio increased significantly (P < 0.01. No differences were found in this respect among SHR and SHR treated with NO donors. These findings demonstrated enhanced hypotension and attenuated relaxation of the conduit artery in response to NO activators in SHR and in SHR treated with NO donors, a response similar to that found in NO-deficient hypertension.

  3. Injection of bradykinin or/and cyclosporine A to hippocampus induces Alzheimer-like phosphorylation of tau and abnormal behavior in rats

    Institute of Scientific and Technical Information of China (English)


    Bradykinin (BK) is a calcium/calmodulin dependent protein kinase Ⅱ (CaMKⅡ) specific activator, and Cyclosporin A (CSA) is reported to suppress protein phosphotase (PP)-2B activity. In vitro studies have shown that CaMKⅡ and PP-2B play an important role in Alzheimer-like phosphorylation of microtube-associated protein tau. To reconstitute an animal model based on the imbalance of protein kinase (s) and protein phosphatase (s) seen in Alzheimer brain, we injected BK and/or CSA into rat hippocampus. The results from behavioral study showed that an obvious disturbance in learning and memory was seen with BK or BK plus CSA injected rats. Moreover, the behavior abnormality appeared earlier in aged rats than young adults of the same kind after the injection. On the other hand, no obvious dysfunction in living and behavior was observed with CSA alone injected rats. The results obtained by immunohistochemical assay indicated that the staining for M4\\, 12E8\\, PHF-1 and CaMKⅡ was stronger, and for Tau-1 was weaker in BK injected rats compared with Control group. It was also found that the binding of M4 and PHF-1 but not 12E8 to tau was significantly increased in CSA injected rats. As the same as BK injection, binding of Tau-1 to tau was decreased after CSA injection. The immunostaining for 12E8\\,PHF-1 and CaMKⅡ was increased, whereas for Tau-1\\, M4\\, and GSK-3 was decreased after combination injection of BK and CSA. In addition, the staining of PP-2B decreased in all the three models. To our knowledge, this is the first data shown in vivo that the activation of CaMKⅡ induces both Alzheimer-like tau phosphorylation and behavioral disturbance.

  4. Coexpression of p53 and Ki 67 and lack of c-erbB2 expression in oral leukoplakias in India. (United States)

    Kumar, Priya; Kane, Shubhada; Rathod, Govind Pomaji


    Oral cancer is commonly preceded by premalignant lesions and conditions. The clinician's ability to identify lesions at an increased risk of cancer development is critical for its control. The purpose of this study was to compare the expression of tumor suppressor gene p53, proliferation marker Ki-67, and oncogene c-erbB2 and to evaluate the relevance of their co-expression in the diagnosis of, and prognosis for, oral leukoplakia. In the present study, the expression of biomarkers was studied immunohistochemically in 55 cases of leukoplakia (26 without dysplasia, 29 with dysplasia) and 10 cases of normal epithelia. The Labeling Indices (LI) of p53 and Ki-67 were found to increase significantly with an increase in the grade of dysplasia. A significant correlation was also found between the LI of p53 and that of Ki-67. It was also observed that c-erbB2 expression was only cytoplasmic, indicating incomplete receptor degradation. Hence, it can be concluded from the present study that the increased expression of p53 and Ki-67 with an increase in the grade of dysplasia suggests that their co-expression may be used for the identification of high-risk lesions. Also, c-erbB2 has no pathogenetic role in early carcinogenesis in the studied population, although incomplete receptor degradation, as evidenced by cytoplasmic staining, may indicate an early change.

  5. Coexpression of p53 and Ki 67 and lack of c-erbB2 expression in oral leukoplakias in India

    Directory of Open Access Journals (Sweden)

    Priya Kumar


    Full Text Available Oral cancer is commonly preceded by premalignant lesions and conditions. The clinician's ability to identify lesions at an increased risk of cancer development is critical for its control. The purpose of this study was to compare the expression of tumor suppressor gene p53, proliferation marker Ki-67, and oncogene c-erbB2 and to evaluate the relevance of their co-expression in the diagnosis of, and prognosis for, oral leukoplakia. In the present study, the expression of biomarkers was studied immunohistochemically in 55 cases of leukoplakia (26 without dysplasia, 29 with dysplasia and 10 cases of normal epithelia. The Labeling Indices (LI of p53 and Ki-67 were found to increase significantly with an increase in the grade of dysplasia. A significant correlation was also found between the LI of p53 and that of Ki-67. It was also observed that c-erbB2 expression was only cytoplasmic, indicating incomplete receptor degradation. Hence, it can be concluded from the present study that the increased expression of p53 and Ki-67 with an increase in the grade of dysplasia suggests that their co-expression may be used for the identification of high-risk lesions. Also, c-erbB2 has no pathogenetic role in early carcinogenesis in the studied population, although incomplete receptor degradation, as evidenced by cytoplasmic staining, may indicate an early change.

  6. EphA4 and EfnB2a maintain rhombomere coherence by independently regulating intercalation of progenitor cells in the zebrafish neural keel. (United States)

    Kemp, Hilary A; Cooke, Julie E; Moens, Cecilia B


    During vertebrate development, the hindbrain is transiently segmented into 7 distinct rhombomeres (r). Hindbrain segmentation takes place within the context of the complex morphogenesis required for neurulation, which in zebrafish involves a characteristic cross-midline division that distributes progenitor cells bilaterally in the forming neural tube. The Eph receptor tyrosine kinase EphA4 and the membrane-bound Ephrin (Efn) ligand EfnB2a, which are expressed in complementary segments in the early hindbrain, are required for rhombomere boundary formation. We showed previously that EphA4 promotes cell-cell affinity within r3 and r5, and proposed that preferential adhesion within rhombomeres contributes to boundary formation. Here we show that EfnB2a is similarly required in r4 for normal cell affinity and that EphA4 and EfnB2a regulate cell affinity independently within their respective rhombomeres. Live imaging of cell sorting in mosaic embryos shows that both proteins function during cross-midline cell divisions in the hindbrain neural keel. Consistent with this, mosaic EfnB2a over-expression causes widespread cell sorting and disrupts hindbrain organization, but only if induced at or before neural keel stage. We propose a model in which Eph and Efn-dependent cell affinity within rhombomeres serve to maintain rhombomere organization during the potentially disruptive process of teleost neurulation.

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

    Directory of Open Access Journals (Sweden)

    Benevolo Maria


    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

  8. Corrosion behavior of pristine and added MgB2 in Phosphate Buffered Saline Solution (United States)

    Batalu, D.; Bojin, D.; Ghiban, B.; Aldica, G.; Badica, P.


    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.

  9. Low-temperature synthesis of MgB2 via powder metallurgy processing (United States)

    Birol, Yucel


    Ball-milled Mg/B2O3 powder blends reveal interpenetrating layers of deformed magnesium and boron oxide grains that are increasingly refined with increasing milling time. Boron oxide is reduced by Mg and MgO thus formed reacts with the remaining B2O3 to produce Mg3(BO3)2 during ball milling for 30 min. Both B2O3 and Mg3(BO3)2 react with Mg to produce MgB2 upon further ball milling. An annealing treatment can be employed when ball milling is performed for less than 1 h as thermal exposure of the ball-milled Mg/B2O3 powder blends also leads to the formation of MgB2. The above reactions take place between 500 and 700 °C when the Mg/B2O3 powder blend is ball milled for 30 min, and between 450 and 550 °C, after ball milling for 1 h. This is a very attractive route owing to processing temperatures where the volatility of Mg is no longer a problem.

  10. Consolidation of B4C-TaB2 eutectic composites by spark plasma sintering

    Directory of Open Access Journals (Sweden)

    Dmytro Demirskyi


    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.

  11. Herschel observations of the Sgr B2 cores: Hydrides, warm CO, and cold dust

    CERN Document Server

    Etxaluze, M; Cernicharo, J; Polehampton, E T; Noriega-Crespo, A; Molinari, S; Swinyard, B M; Wu, R; Bally, J


    Sagittarius B2 (Sgr B2) is one of the most massive and luminous star-forming regions in the Galaxy and shows chemical and physical conditions similar to those in distant extragalactic starbursts. We present large-scale far-IR/submm photometric images and spectroscopic maps taken with the PACS and SPIRE instruments onboard Herschel. The spectra towards the Sgr B2 star-forming cores, B2(M) and B2(N), are characterized by strong CO line emission, emission lines from high-density tracers (HCN, HCO+, and H2S), [N II] 205 um emission from ionized gas, and absorption lines from hydride molecules (OH+, H2O+, H2O, CH+, CH, SH+, HF, NH, NH2, and NH3). The rotational population diagrams of CO suggest the presence of two gas temperature components: an extended warm component, which is associated with the extended envelope, and a hotter component, which is seen towards the B2(M) and B2(N) cores. As observed in other Galactic Center clouds, the gas temperatures are significantly higher than the dust temperatures inferred f...


    Institute of Scientific and Technical Information of China (English)


    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.

  13. 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


    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 .

  14. Neutron diffraction studies of magnetic ordering in superconducting ErNi2B2C and TmNi2B2C in an applied magnetic field

    DEFF Research Database (Denmark)

    Toft, Katrine Nørgaard

    along [110], the magnetic structure rotates a small angle of 0.5 degrees away from the symmetrydirection. TmNi2B2C: A magnetic field applied in the [100] direction suppresses the zero field magnetic structure QF = (0.094,0.094,0) (TN = 1.6 K), in favor of the Fermi surface nesting structure QN = (0......The field-induced magnetic structures of ErNi2B2C and TmNi2B2C in are especially interesting because the field suppresses the superconducting order parameter and therefore the magnetic properties can be studied while varying the strength ofsuperconductivity. ErNi2B2C: For magnetic fields along all...... three symmetry directions, the observed magnetic structures have a period corresponding to the Fermi surface nesting structure. The phase diagrams present all the observed magnetic structures.Two results remain unresolved: 1. When applying the magnetic field along [010], the minority domain (QNB = (0,Q...

  15. Superconducting Properties and Microstructure in MgB2 Bulks, Wires and Tapes

    Institute of Scientific and Technical Information of China (English)

    冯勇; 阎果; 赵勇; 吴晓京; 周廉; 张平祥


    We prepared a series of MgB2 bulk samples under different temperatures, holding time and increasing rates in temperature by the solid state reaction. The thermodynamic behavior and phase formation in the Mg-B system were studied by using DTA,XRD and SEM. The results indicate that the formation of the MgB2 phase is very fast and the high increasing rate in temperature is necessary to obtain high quality MgB2. In addition, the effects of the Zr-doping in Mg1-xZrxB2 bulk samples fabricated by the solid state reaction at ambient pressure on phase compositions, microstructure and flux pinning behavior were investigated by using XRD, SQUID magnetometer, SEM and TEM. Critical current density Jc can be significantly enhanced by the Zr-doping and the best data are achieved in Mg0.9Zr0.1B2. For this sample, Jc values are remarkably improved to 1.83×106 A/cm2 in self-field and 5.51×105 A/cm2 in 1 T at 20 K. Also, high quality MgB2/Ta/Cu wires and tapes with and without Ti-doping, MgB2/Fe wires and 18 filament MgB2/NbZr/Cu tapes were fabricated by the powder-in-tube (PIT) method at ambient pressure. The phase compositions, microstructure features and flux pinning properties were studied. The results suggest that Fe is thebest metal for these sheaths. MgB2/Fe wires exhibit very high Jc at high temperatures and high fields. Jc values reach as high as 1.43×105 A/cm2 (4.2 K, 4 T) and 3.72×104 A/cm2 (15 K, 4 T).

  16. Molecular cloning and characterization of SoxB2 gene from Zhikong scallop Chlamys farreri (United States)

    He, Yan; Bao, Zhenmin; Guo, Huihui; Zhang, Yueyue; Zhang, Lingling; Wang, Shi; Hu, Jingjie; Hu, Xiaoli


    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.

  17. Depletion of the xynB2 gene upregulates β-xylosidase expression in C. crescentus. (United States)

    Corrêa, Juliana Moço; Mingori, Moara Rodrigues; Gandra, Rinaldo Ferreira; Loth, Eduardo Alexandre; Seixas, Flávio Augusto Vicente; Simão, Rita de Cássia Garcia


    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.

  18. 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


    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

  19. Dendrite crystal morphology evolution mechanism of β-BaB2O4 crystal

    Institute of Scientific and Technical Information of China (English)

    HE ChongJun; ZHONG WeiZhuo; LIU YouWen


    Existence of [B3-O6]3- hexagonal ring growth unit in melt solution of β-BaB2O4 crystal was proved by the results of high temperature Raman measurements. A morphology evolution process of β-BaB2O4 crys-tal was observed by a high temperature in-situ observation device. The crystal morphology varied with the supersaturation of growth melt solution. The mechanism of β-BaB2O4 crystal morphology evolution was analyzed through the growth unit model.

  20. Dendrite crystal morphology evolution mechanism of β-BaB2O4 crystal

    Institute of Scientific and Technical Information of China (English)


    Existence of [B3-O6]3- hexagonal ring growth unit in melt solution of β-BaB2O4 crystal was proved by the results of high temperature Raman measurements.A morphology evolution process of β-BaB2O4 crys-tal was observed by a high temperature in-situ observation device.The crystal morphology varied with the supersaturation of growth melt solution.The mechanism of β-BaB2O4 crystal morphology evolution was analyzed through the growth unit model.

  1. Improving magnetic properties of MgB2 bulk superconductors by synthetic engine oil treatment (United States)

    Taylan Koparan, E.; Savaskan, B.; Yanmaz, E.


    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.

  2. Improved critical current density of MgB2--carbon nanotubes composite. (United States)

    Shekhar, Chandra; Giri, Rajiv; Malik, S K; Srivastav, O N


    In the present study, we report a systematic study of doping/admixing of carbon nanotubes (CNTs) in different concentrations in MgB2. The composite material corresponding to MgB2-x at.% CNTs (35 at.% > or = x > or = 0 at.%) have been prepared by solid-state reaction at ambient pressure. All the samples in the present investigation have been subjected to structural/microstructural characterization employing XRD, Scanning electron microscopic (SEM), and Transmission electron microscopic (TEM) techniques. The magnetization measurements were performed by Physical property measurement system (PPMS) and electrical transport measurements have been done by the four-probe technique. The microstructural investigations reveal the formation of MgB2-carbon nanotube composites. A CNT connecting the MgB2 grains may enhance critical current density due to its size (approximately 5-20 nm diameter) compatible with coherence length of MgB2 (approximately 5-6 nm) and ballistic transport current carrying capability along the tube axis. The transport critical current density (Jct) of MgB2 samples with varying CNTs concentration have been found to vary significantly e.g., Jct of the MgB2 sample with 10 at.% CNT addition is approximately 2.3 x 10(3) A/cm2 and its value for MgB2 sample without CNT addition is approximately 7.2 x 102 A/cm2 at 20 K. In order to study the flux pinning effect of CNTs doping/ admixing in MgB2, the evaluation of intragrain critical current density (JJ) has been carried out through magnetic measurements on the fine powdered version of the as synthesized samples. The optimum result on Jc is obtained for 10 at.% CNTs admixed MgB2 sample at 5 K, the Jc reaches approximately 5.2 x 10(6) A/cm2 in self field, -1.6 x 10(6) A/cm2 at 1 T, approximately 2.9 x 10(5) A/cm2 at 2.6 T, and approximately 3.9 x 10(4) A/cm2 at 4 T. The high value of intragrain Jc in 10 at.% CNTs admixed MgB2 superconductor has been attributed to the incorporation of CNTs into the crystal matrix of

  3. FASN, ErbB2-mediated glycolysis is required for breast cancer cell migration. (United States)

    Zhou, Lan; Jiang, Sufang; Fu, Qiang; Smith, Kelly; Tu, Kailing; Li, Hua; Zhao, Yuhua


    Both fatty acid synthase (FASN) and ErbB2 have been shown to promote breast cancer cell migration. However, the underlying molecular mechanism remains poorly understood and there is no reported evidence that directly links glycolysis to breast cancer cell migration. In this study, we investigated the role of FASN, ErbB2-mediated glycolysis in breast cancer cell migration. First, we compared lactate dehydrogenase A (LDHA) protein levels, glycolysis and cell migration between FASN, ErbB2-overexpressing SK-BR-3 cells and FASN, ErbB2-low-expressing MCF7 cells. Then, SK-BR-3 cells were treated with cerulenin (Cer), an inhibitor of FASN, and ErbB2, LDHA protein levels, glycolysis, and cell migration were detected. Next, we transiently transfected ErbB2 plasmid into MCF7 cells and detected FASN, LDHA protein levels, glycolysis and cell migration. Heregulin-β1 (HRG-β1) is an activator of ErbB2 and 2-deoxyglucose (2-DG) and oxamate (OX) are inhibitors of glycolysis. MCF7 cells were treated with HRG-β1 alone, HRG-β1 plus 2-DG, OX or cerulenin and glycolysis, and cell migration were measured. We found that FASN, ErbB2-high-expressing SK-BR-3 cells displayed higher levels of glycolysis and migration than FASN, ErbB2-low-expressing MCF7 cells. Inhibition of FASN by cerulenin impaired glycolysis and migration in SK-BR-3 cells. Transient overexpression of ErbB2 in MCF7 cells promotes glycolysis and migration. Moreover, 2-deoxyglucose (2-DG), oxamate (OX), or cerulenin partially reverses heregulin-β1 (HRG-β1)-induced glycolysis and migration in MCF7 cells. In conclusion, this study demonstrates that FASN, ErbB2-mediated glycolysis is required for breast cancer cell migration. These novel findings indicate that targeting FASN, ErbB2-mediated glycolysis may be a new approach to reverse breast cancer cell migration.

  4. 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


    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.

  5. Glass formation and crystallization of high lead content PbO-B2O3 compositions (United States)

    Weinberg, Michael C.; Smith, Gary L.; Neilson, George F.


    The glass-forming and undercooling ability of PbO-B2O3 melts in the 2PbO.B2O3 to 4PbO.B2O3 composition range were studied. The glass formation propensities were investigated as a function of cooling rate and sample mass. A qualitative investigation of the crystallization process(es) preventing glass formation was made, and it was concluded that under normal circumstances heterogeneous nucleation was the common occurrence. Hence, it was concluded that such compositions are prime candidates for containerless experiments aboard the Space Shuttle.

  6. erbB-2 autophosphorylation is required for mitogenic action and high-affinity substrate coupling

    DEFF Research Database (Denmark)

    Segatto, O; Lonardo, F; Helin, K;


    -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......B-2 substrate, although with a delayed time course, indicating that the 5P mutation decreased the affinity of the erbB-2 kinase for this substrate. This conclusion was further supported by the inability of the 5P mutant to associate with PLC-gamma in co-immunoprecipitation experiments. We infer...

  7. Using service design methods for B2b service brand concept development: Case company


    Molina Escalante, Hugo


    A short time before this study was initiated, a small B2b service company had just began op-erating its business without a brand of it’s own. The company owners were looking to design an innovative brand for their business. The purpose of this thesis was to develop the brand for this service Company in the B2b context, using practical service design and Strategic design research methods. This thesis report represents a framework for developing a B2b service brand using research methods c...

  8. A New Method for the Preparation of MgB2 Superconducting Tapes

    Institute of Scientific and Technical Information of China (English)

    许加迪; 王淑芳; 周岳亮; 戴守愚; 陈正豪; 崔大复; 吕惠宾; 朱亚斌; 何萌; 杨国桢


    Superconducting MgB2/Ta tapes with a critical temperature of 38 K have been prepared successfully by a two-step method. Boron/Ta tapes were fabricated by electrophoresis followed by a post-annealing process in magnesium vapour. The critical current density is 1.7 × 104 A/cm2 in zero field at 5K. Scanning electron microscopy and x-ray diffraction analysis reveal a dense flat surface with (101) orientated growth of the MgB2 phase in our MgB2/Ta tapes.

  9. An Empirical Examination of Reverse Auction Appropriateness in B2B Source Selection (United States)


    Measures of Marketing Constructs," Journal of Marketing Research, Vol. 16, No.2, pp. 64 - 73. Cohn, L. (2000), " B2B : The Hottest Net Bet Yet...AND SUBTITLE 5. FUNDING NUMBERS AN EMPIRICAL EXAMINATION OF REVERSE AUCTION APPROPRIATENESS IN B2B SOURCE SELECTION. 6. AUTHOR(S) MAJ HAWKINS TIMOTHY...Examination of Reverse Auction Appropriateness in B2B Source Selection D :7;TZU IUT•ITM STATER,;77TIT A Approved for Puhtic P-•-!,ase Distribution

  10. The Importance of Brand on B2B Markets: Case Study of Hilti


    Konečný, Martin


    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...

  11. The protective activity of noscapine on renal ischemia–reperfusion injury in male Wistar rat


    Mehrangiz Khanmoradi; Seyyed Ali Mard; Nahid Aboutaleb; Malihe Nobakht; Masoud Mahmoudian


    Objective(s): Bradykinin is a part of the kinin-kallikrein system which is involved in ischemia-reperfusion injury via B1 and B2 receptors. Noscapine is a non-competitive antagonist of bradykinin receptors. Noscapine has been reported to to be able to protect some organs against ischemia-reperfusion injury but its effect on renal ischemia-reperfusion injury (RIR) in rats is unknown. Therefore, the present study was designed to evaluate the effect of noscapine on renal ischemia-reperfusion inj...

  12. 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


    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.

  13. Antihyperalgesic effect of CB1 receptor activation involves the modulation of P2X3 receptor in the primary afferent neuron. (United States)

    Oliveira-Fusaro, Maria Cláudia Gonçalves; Zanoni, Cristiane Isabel Silva; Dos Santos, Gilson Gonçalves; Manzo, Luis Paulo; Araldi, Dionéia; Bonet, Ivan José Magayewski; Tambeli, Cláudia Herrera; Dias, Elayne Vieira; Parada, Carlos Amilcar


    Cannabinoid system is a potential target for pain control. Cannabinoid receptor 1 (CB1) activation play a role in the analgesic effect of cannabinoids once it is expressed in primary afferent neurons. This study investigates whether the anti-hyperalgesic effect of CB1 receptor activation involves P2X3 receptor in primary afferent neurons. Mechanical hyperalgesia was evaluated by electronic von Frey test. Cannabinoid effect was evaluated using anandamide or ACEA, a non-selective or a selective CB1 receptor agonists, respectively; AM251, a CB1 receptor antagonist, and antisense ODN for CB1 receptor. Calcium imaging assay was performed to evaluated α,β-meATP-responsive cultured DRG neurons pretreated with ACEA. Anandamide or ACEA administered in peripheral tissue reduced the carrageenan-induced mechanical hyperalgesia. The reduction in the carrageenan-induced hyperalgesia induced by ACEA was completely reversed by administration of AM251 as well as by the intrathecal treatment with antisense ODN for CB1 receptor. Also, ACEA reduced the mechanical hyperalgesia induced by bradykinin and by α,β-meATP, a P2X3 receptor non-selective agonist, but not by tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β) and chemokine-induced chemoattractant-1 (CINC-1). Finally, CB1 receptors are co-localized with P2X3 receptors in DRG small-diameter neurons and the treatment with ACEA reduced the number of α,β-meATP-responsive cultured DRG neurons. Our data suggest that the analgesic effect of CB1 receptor activation is mediated by a negative modulation of the P2X3 receptor in the primary afferent neurons.

  14. Electronic structure of MgB2 from angle-resolved photoemission spectroscopy. (United States)

    Uchiyama, H; Shen, K M; Lee, S; Damascelli, A; Lu, D H; Feng, D L; Shen, Z-X; Tajima, S


    The first angle-resolved photoemission spectroscopy results from MgB2 single crystals are reported. Along the GammaK and GammaM directions, we observed three distinct dispersive features approaching the Fermi energy. These can be assigned to the theoretically predicted sigma (B 2p(x,y)) and pi (B 2p(z)) bands. In addition, a small parabolic-like band is detected around the Gamma point, which can be attributed to a surface-derived state. The overall agreement between our results and the band calculations suggests that the electronic structure of MgB2 is of a conventional nature, thus implying that electron correlations are weak and may be of little importance to superconductivity in this system.

  15. Coherent phonon decay and the boron isotope effect for MgB2. (United States)

    Alarco, Jose A; Talbot, Peter C; Mackinnon, Ian D R


    Ab initio DFT calculations for the phonon dispersion (PD) and the phonon density of states (PDOS) of the two isotopic forms ((10)B and (11)B) of MgB2 demonstrate that use of a reduced symmetry super-lattice provides an improved approximation to the dynamical, phonon-distorted P6/mmm crystal structure. Construction of phonon frequency plots using calculated values for these isotopic forms gives linear trends with integer multiples of a base frequency that change in slope in a manner consistent with the isotope effect (IE). Spectral parameters inferred from this method are similar to that determined experimentally for the pure isotopic forms of MgB2. Comparison with AlB2 demonstrates that a coherent phonon decay down to acoustic modes is not possible for this metal. Coherent acoustic phonon decay may be an important contributor to superconductivity for MgB2.

  16. Epitaxial growth of MgB2 films at ambient temperature (United States)

    Shishido, Hiroaki; Yoshida, Takuya; Nakagami, Takatoshi; Ishida, Takekazu

    We grew crystalline MgB2 thin films using molecular beam epitaxy at a low substrate temperature of 110 °C under an ultrahigh vacuum of about 10-6 Pa. MgB2 thin films were deposited on the (001) surface of a 4H-SiC substrate with an epitaxial Mg buffer layer. The epitaxial growth was confirmed by X-ray diffraction measurements. MgB2 thin films show a sharp superconducting transition at 27.2 K, with a relatively narrow superconducting transition width ΔTc = 0.9 K. The growth temperature was lower than any in prior reports on superconducting MgB2 thin films. The presence of the epitaxial Mg buffer layer is crucial for reducing the epitaxial temperature.

  17. 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


    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.

  18. Rapid determination of vitamin B2 and B12 in human urine by isocratic liquid chromatography. (United States)

    Mandal, Santi M; Mandal, Mahitosh; Ghosh, Ananta K; Dey, Satyahari


    A simple and rapid method for the identification and quantification of vitamin B(2) and B(12) in human urine has been developed using reverse phase high performance liquid chromatography (HPLC) and the peaks identity were confirmed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). HPLC separation was performed in single wavelength detector (lambda(365)) mode and separated isocratically using mobile phase methanol: 1mM aqueous TFA (1:4) in C18 column. The calibration graphs plotted with different concentrations of vitamin B(2) and B(12) was linear with a correlation coefficients (r(2))=0.9975 and 0.9985, respectively. The recoveries of vitamin B(2) and B(12) were above 87% and 90%, respectively. The results of this present study suggest that the proposed method may be simple and convenient way of identifying and quantifying vitamin B(2) and B(12) from human urine.

  19. Data of evolutionary structure change: 1AW2B-2VENA [Confc[Archive

    Lifescience Database Archive (English)


  20. Superior homogeneity of trapped magnetic field in superconducting MgB2 bulk magnets (United States)

    Ishihara, A.; Akasaka, T.; Tomita, M.; Kishio, K.


    Homogeneity of trapped magnetic field in radial and circumferential directions of high temperature superconducting bulk magnets, MgB2 (T c ˜38.3 K) and YBa2Cu3O y (T c ˜91.5 K), have been measured. In polycrystalline MgB2 bulks, the circularity of trapped magnetic field in a cylindrical disk is over 97% at 20-32.5 K, while that of YBa2Cu3O y was ˜87% at 77 K. Magnetic field distribution of MgB2 bulk was satisfactorily homogeneous and these measurements suggest MgB2 bulks with highly efficient cryocoolers should be very useful for novel high field permanent magnet applications.

  1. Molecular-Beam Epitaxially Grown MgB2 Thin Films and Superconducting Tunnel Junctions

    Directory of Open Access Journals (Sweden)

    Jean-Baptiste Laloë


    Full Text Available Since the discovery of its superconducting properties in 2001, magnesium diboride has generated terrific scientific and engineering research interest around the world. With a of 39 K 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.

  2. Anisotropy oxidation of textured ZrB2–MoSi2 ceramics

    DEFF Research Database (Denmark)

    Liu, Hai-Tao; Zou, Ji; Ni, De Wei


    Oxidation behavior of hot forged textured ZrB2–20vol% MoSi2 ceramics with platelet ZrB2 grains was investigated at 1500°C for exposure time from 0.5 to 12h. Compared to untextured ceramics, the textured ceramics showed obvious anisotropic oxidation behavior and the surface normal to the hot forging...... pressure demonstrated better oxidation resistance. Such improvement in the oxidation resistance is primarily considered as a higher intrinsic ZrB2 atomic density on the orientated {00l} planes in the textured ceramics. It is expectable that the anisotropic textured ZrB2–MoSi2 ceramics can offer better...

  3. 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


    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...... 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...... to be related to IBD, UC or CD. CONCLUSIONS: Our study reveals that intestinal colonization with phylogenetic group B2 E. coli is associated with UC. Due to the design, we are unable to determine if the colonization with B2 E. coli leads to the development of the disease or the disease increases the risk...

  4. Ferromagnetic enhancement in the hexagonal Ce(Rh1-xIrx)3B2 system (United States)

    Hsu, S. W.; Ku, H. C.


    Electrical resistivity, magnetization, and crystallographic measurements have been carried out for the pseudoternary system Ce(Rh1-xIrx)3B2. A single-phase hexagonal CeCo3B2-type structure persists from x=0.0 up to x0.95. The ferromagnetic Curie temperature Tc is enhanced from 115 K for CeRh3B2 to 125 K for Ce(Rh0.8Ir0.2)32, then decreases slowly to 118 K at x=0.5 before decreasing sharply to 69 K at x=0.67, even though the magnetic moment per Ce ion decreases monotonically with increasing Ir substitution. The Tc of 125 K in Ce(Rh0.8Ir0.2)3B2 is the highest magnetic-ordering temperature observed so far for all Ce-based systems with nonmagnetic constituents.

  5. Managing Innovation Through Social Media in B2B SME-Context

    DEFF Research Database (Denmark)

    Lutz, Salla; Madsen, Svend Ole; Brink, Tove


    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....

  6. Safety Analysis Report: X17B2 beamline Synchrotron Medical Research Facility

    Energy Technology Data Exchange (ETDEWEB)

    Gmuer, N.F.; Thomlinson, W.


    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)

  7. Proton Mobility in b2 Ion Formation and Fragmentation Reactions of Histidine-Containing Peptides (United States)

    Nelson, Carissa R.; Abutokaikah, Maha T.; Harrison, Alex G.; Bythell, Benjamin J.


    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.

  8. The Importance of Brand on B2B Markets: Expert Interviews with Hilti AG Managers

    Directory of Open Access Journals (Sweden)

    Martin Konečný


    Full Text Available This paper investigates the importance of brand building in the business-to-business world. Not only B2C companies must take branding into account and put it among their top priorities in order to survive and succeed on the market. The first part of the article deals with the theoretical background of brand importance and market specifics of B2B markets and results in the setting of two hypotheses. The following research has to find out how the managers of a pure business-to-business company perceive the importance of a brand; moreover, it has to evaluate the importance of eight specific brand building factors. Fourteen expert interviews document the growing of brands in the B2B market and their main aspects. At the end of the article, we will focus on future implications for B2B management.

  9. Dehybridization of the 4f shell in Si-substituted CeRh3B2 (United States)

    Malik, S. K.; Shenoy, G. K.; Dhar, S. K.; Paulose, P. L.; Vijayaraghavan, R.


    The compound CeRh3B2 is known to order magnetically with an unusually high Curie temperature (TC) of 115 K and a low saturation moment of about 0.4μB. We have studied the magnetic behavior of the system CeRh3(B1-xSix)2 (0CeRh3B2 arises because of the Ce 4f hybridization with the neighboring ligands.

  10. Study of magnetic behaviour of CeRh3B2 using111Cd probe (United States)

    Nyayate, M. N.; Devare, S. H.; Devare, H. G.


    Using111Cd probe nuclei, the transferred H hf( T) is measured down to 35 K in CeRh3B2 using TDPAC technique. The angle β between the EFG and the direction of magnetization is obtained to be 90°. The observed small H hf( T) may be a consequence of the reduced moment on Ce in CeRh3B2.

  11. High Upper Critical Field and Irreversibility Field in MgB2 Coated-Conductor Fibers (United States)


    conductor fibers deposited by hybrid physical- chemical vapor deposition on SiC fibers. The coating is polycrystalline and composed of elongated...High upper critical field and irreversibility field in MgB2 coated -conductor fibers V. Ferrando,a P. Orgiani,b A. V. Pogrebnyakov, J. Chen, Qi Li...2005; accepted 14 November 2005; published online 14 December 2005 We report on structural and superconducting properties of round MgB2 coated

  12. Drivers of relationships affecting B2B firms in an e-commerce environment

    Directory of Open Access Journals (Sweden)

    Irene Samanta


    Full Text Available The advent of the internet has created numerous opportunities for B2B marketing professionals to enhance current marketing practices, including electronic relationships. However, the investigation of e-relationships and the factors that influence e-relationships in an internet environment is scant. Further, there appears to be no investigation of this phenomenon within the context of Greek B2B Medium-sized firms (MSF. Τhe research problem investigated in this research is: “Which drivers in B2B e-commerce use affect inter-firm relationships in medium-sized B2B firms?”. A framework for B2B e-commerce relationships in a changing and globalized environment was synthesised and integrated with the literature about relationship marketing to arrive at the following research issues: “How do relationship marketing drivers affect the management of B2B e-relationships?”. An explanatory quantitative research approach was used and quantitative data was collected from B2B firms in Greece, which represents a case of e-commerce progress during the last six years. Regarding social exchange, some important differences emerge where cooperation between B2B e-commerce firms is concerned. Suppliers engaged in electronic commerce are more committed and oriented to a long-term relationship than buyers, based on both previous and current experience with them. Confidence in the relationships, consistency and honesty with their obligations and the exchange of reliable, trustworthy information and advisory services between firms are important factors in the development and establishment of their e-relationships. The main contribution of this research is the development of a theoretical framework for e-relationships in medium-sized Β2Β firms. That framework is the first rigorously researched step towards understanding the importance of these powerful streams of relationship drivers in total, and the business activity of e-marketing and electronic relationships.

  13. Framing agenda for business model innovation research from the B2B context


    Neupane, Ganesh Prasad; Haugland, Sven A.


    This paper reviews the literature on business models in the business-to-business (B2B) context and proposes a research agenda that can be explored by future studies using various management and organizational theories. We outline four research themes and seven research topics for research on business model innovations in the B2B context. Further studies on these topics can make significant contributions to the business model literature.

  14. An ANFIS-based on B2C electronic commerce transaction

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Juan, E-mail: [Department of Mathematics and Computer Science, Fuqing Branch of Fujian Normal University, Fuqing 350300 (China); Liu, Chenlian, E-mail: [School of Mathematics and Computer Science, Long Yan University, Longyan 364012 (China); Guo, Yongning, E-mail: [Fuqing Branch of Fujian Normal University, Fuqing 350300 (China)


    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.

  15. An ANFIS-based on B2C electronic commerce transaction (United States)

    Lin, Juan; Liu, Chenlian; Guo, Yongning


    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.

  16. High critical currents in iron-clad superconducting MgB2 wires. (United States)

    Jin, S; Mavoori, H; Bower, C; van Dover, R B


    Technically useful bulk superconductors must have high transport critical current densities, Jc, at operating temperatures. They also require a normal metal cladding to provide parallel electrical conduction, thermal stabilization, and mechanical protection of the generally brittle superconductor cores. The recent discovery of superconductivity at 39 K in magnesium diboride (MgB2) presents a new possibility for significant bulk applications, but many critical issues relevant for practical wires remain unresolved. In particular, MgB2 is mechanically hard and brittle and therefore not amenable to drawing into the desired fine-wire geometry. Even the synthesis of moderately dense, bulk MgB2 attaining 39 K superconductivity is a challenge because of the volatility and reactivity of magnesium. Here we report the successful fabrication of dense, metal-clad superconducting MgB2 wires, and demonstrate a transport Jc in excess of 85,000 A cm-2 at 4.2 K. Our iron-clad fabrication technique takes place at ambient pressure, yet produces dense MgB2 with little loss of stoichiometry. While searching for a suitable cladding material, we found that other materials dramatically reduced the critical current, showing that although MgB2 itself does not show the 'weak-link' effect characteristic of the high-Tc superconductors, contamination does result in weak-link-like behaviour.

  17. Quantum confinement induced band gaps in MgB2 nanosheets (United States)

    Xu, Bo Z.; Beckman, Scott P.


    The discovery of two-dimensional semiconducting materials, a decade ago, spawned an entire sub-field within solid-state physics that is focused on the development of nanoelectronics. Here we present a new class of semiconducting two-dimensional material based on hexagonal MgB2. Although MgB2 is a semimetal, similar to the other well-studied transition metal diborides, we demonstrate that, unlike the transition metal diborides, thinning MgB2, to create nanosheets, opens a band gap in the density of states. We predict that a 7 Å thick MgB2 nanosheet will have a band gap of 0.51 eV. MgB2 nanosheets differ from other two-dimensional semiconductors in that the band gap is introduced by (001) surfaces and is opened by the quantum confinement effect. The implications of these findings are that nanostructured MgB2 is not merely a new composition, but also has intrinsic mechanisms for tuning its electronic properties, which may facilitate the development of nanoelectronics.

  18. Crystal Structures, Stabilities, Electronic Properties, and Hardness of MoB2: First-Principles Calculations. (United States)

    Ding, Li-Ping; Shao, Peng; Zhang, Fang-Hui; Lu, Cheng; Ding, Lei; Ning, Shu Ya; Huang, Xiao Fen


    On the basis of the first-principles techniques, we perform the structure prediction for MoB2. Accordingly, a new ground-state crystal structure WB2 (P63/mmc, 2 fu/cell) is uncovered. The experimental synthesized rhombohedral R3̅m and hexagonal AlB2, as well as theoretical predicted RuB2 structures, are no longer the most favorite structures. By analyzing the elastic constants, formation enthalpies, and phonon dispersion, we find that the WB2 phase is thermodynamically and mechanically stable. The high bulk modulus B, shear modulus G, low Poisson's ratio ν, and small B/G ratio are benefit to its low compressibility. When the pressure is 10 GPa, a phase transition is observed between the WB2-MoB2 and the rhombohedral R3̅m MoB2 phases. By analyzing the density of states and electron density, we find that the strong covalent is formed in MoB2 compounds, which contributes a great deal to its low compressibility. Furthermore, the low compressibility is also correlated with the local buckled structure.

  19. Erythropoietin promotes bone formation through EphrinB2/EphB4 signaling. (United States)

    Li, C; Shi, C; Kim, J; Chen, Y; Ni, S; Jiang, L; Zheng, C; Li, D; Hou, J; Taichman, R S; Sun, H


    Recent studies have demonstrated that erythropoietin (EPO) has extensive nonhematopoietic biological functions. However, little is known about how EPO regulates bone formation, although several studies suggested that EPO can affect bone homeostasis. In this study, we investigated the effects of EPO on the communication between osteoclasts and osteoblasts through the ephrinB2/EphB4 signaling pathway. We found that EPO slightly promotes osteoblastic differentiation with the increased expression of EphB4 in ST2 cells. However, EPO increased the expression of Nfatc1 and ephrinB2 but decreased the expression of Mmp9 in RAW264.7 cells, resulting in an increase of ephrinB2-expressing osteoclasts and a decrease in resorption activity. The stimulation of ephrinB2/EphB4 signaling via ephrinB2-Fc significantly promoted EPO-mediated osteoblastic differentiation in ST2 cells. EphB4 knockdown through EphB4 shRNA inhibited EPO-mediated osteoblastic phenotypes. Furthermore, in vivo assays clearly demonstrated that EPO efficiently induces new bone formation in the alveolar bone regeneration model. Taken together, these results suggest that ephrinB2/EphB4 signaling may play an important role in EPO-mediated bone formation.

  20. Degradation of aromatic compounds and degradative pathway of 4-nitrocatechol by Ochrobactrum sp. B2. (United States)

    Zhong, Qiuzan; Zhang, Haiyan; Bai, Wenqin; Li, Mei; Li, Baotong; Qiu, Xinghui


    The potential capacity of a soil methyl parathion-degrading bacterium strain, Ochrobactrum sp. B2, for degrading various aromatic compounds were investigated. The results showed B2 was capable of degrading diverse aromatic compounds, but amino-substituted benzene compounds, at a concentration up to 100 mg L(-1) in 4 days. B2 could use 4-nitrocatechol (4-NC) as a sole carbon and energy source with release of nitrite ion. The pathway for 4-NC degradation via 1,2,4-benzenetriol (BT) and hydroquinone (HQ) formation in B2 was proposed based on the identification and quantification of intermediates by gas chromatography-mass spectrometry (GC-MS), and high performance liquid chromatography (HPLC). Degradation studies carried out on a plasmid-cured derivative showed that the genes for 4-NC degradative pathway was plasmid-borne in B2, suggesting that B2 degrades both p-nitrophenol and 4-NC by enzymes encoded by genes on the same plasmid.

  1. Investigation of lauric acid dopant as a novel carbon source in MgB 2 wire (United States)

    Lee, C. M.; Lee, S. M.; Park, G. C.; Joo, J.; Lim, J. H.; Kang, W. N.; Yi, J. H.; Jun, B.-H.; Kim, C.-J.


    We fabricated lauric acid (LA) doped MgB2 wires and investigated the effects of the LA doping. For the fabrication of the LA-doped MgB2 wires, B powder was mixed with LA at 0-5 wt.% of the total amount of MgB2 using an organic solvent, dried, and then the LA-treated B and Mg powders were mixed stoichiometrically. The powder mixture was loaded into an Fe tube and the assemblage was drawn and sintered at 900 °C for 3 h under an argon atmosphere. We observed that the LA doping induced the substitution of C for the B sites in MgB2 and that the actual content of C increased monotonically with increasing LA doping level. The LA-doped MgB2 wires exhibited a lower critical temperature (Tc), but better critical current density (Jc) behavior in a high magnetic field: the 5 wt.% LA-doped sample had a Jc value of 5.32 × 103 A/cm2, which was 2.17 times higher than that of the pristine sample (2.45 × 103 A/cm2) at 5 K and 6 T, suggesting that LA is an effective C dopant in MgB2 for enhancing the high-field Jc performance.

  2. Alginate/chitosan nanoparticles for encapsulation and controlled release of vitamin B2. (United States)

    Azevedo, Maria A; Bourbon, Ana I; Vicente, António A; Cerqueira, Miguel A


    This work aims at evaluating encapsulation and controlled release of vitamin B2 from alginate/chitosan nanoparticles. Ionotropic polyelectrolyte pre-gelation was used as production method being chitosan and alginate used as main materials. Nanoparticles were characterized in terms of average size, polydispersity index (PDI), zeta potential and vitamin entrapment efficiency. The average size for alginate/chitosan nanoparticles was 119.5±49.9nm for samples without vitamin B2 and 104.0±67.2nm with the encapsulation of vitamin B2, presenting a PDI of 0.454±0.066 and 0.319±0.068, respectively. The nanoparticles showed encapsulation efficiency and loading capacity values of 55.9±5.6% and 2.2±0.6%, respectively. Release profiles were evaluated at different conditions showing that the polymeric relaxation was the most influent phenomenon in vitamin B2 release. In order to study their stability nanoparticles were stored at 4°C being particles sizes and PDI evaluated during 5 months showing the results that vitamin B2-loaded nanoparticles are more stable (in terms of size and PDI) than nanoparticles without vitamin B2.

  3. Magnetic and NMR investigation of RRh3B2 (R=La to Gd) compounds (United States)

    Malik, S. K.; Dhar, S. K.; Vijayaraghavan, R.; Wallace, W. E.


    Magnetization (4.2 to 300 K) and 11B paramagnetic NMR (77 to 300 K) studies have been carried out on ternary borides RRh3B2 (R=La to Gd). These compounds crystallize in the CeCo3B2-type structure. From cell volume considerations Ce is in a mixed valent/quadrivalent state while the rest of the rare earth ions are in a trivalent state. With the exception of La and Pr compounds, all other compounds are found to order magnetically. From the high values of the ratio of paramagnetic moment to ordered state moment, the magnetic ordering is inferred to be the itinerant type in CeRh3B2 and EuRh3B2. In Nd and Gd compounds, magnetization data reveal that magnetic ordering is associated with the rare earth sublattice. A complex behavior of magnetization is observed in SmRh3B2. A first order quadrupole split 11B NMR spectrum is observed in Ce, Pr, Nd, and Sm compounds. The boron Knight shift in all these compounds is small and, within the limits of experimental error, scales linearly with susceptibility in Pr and Nd compounds. A temperature independent Knight shift is observed in SmRh3B2, indicating the influence of strong crystal fields.

  4. Wettability and Reactivity of ZrB2 Substrates with Liquid Al (United States)

    Nowak, R.; Sobczak, N.; Bruzda, G.; Wojewoda-Budka, J.; Litynska-Dobrzynska, L.; Homa, M.; Kaban, I.; Xi, L.; Jaworska, L.


    Wetting characteristics of the Al/ZrB2 system were experimentally determined by the sessile drop method with application of separate heating of the ZrB2 and Al samples and combined with in situ cleaning of Al drop from native oxide film directly in vacuum chamber. The tests were performed in ultrahigh vacuum of 10-6 mbar at temperatures 710, 800, and 900 °C as well as in flowing inert gas (Ar) atmosphere at 1400 °C. The results evidenced that liquid Al does not wet ZrB2 substrate at 710 and 800 °C, forming high contact angles ( θ) of 128° and 120°, respectively. At 900 °C, wetting phenomenon ( θ contact angle decreases monotonically to the final value of 80°. At 1400 °C, wetting takes place immediately after drop deposition with a fast decrease in the contact angle to 76°. The solidified Al/ZrB2 couples were studied by scanning and transmission electron microscopy coupled with x-ray energy diffraction spectroscopy. Structural characterization revealed that only in the Al/ZrB2 couple produced at the highest temperature of 1400 °C new phases (Al3Zr, AlB2 and α-Al2O3) were formed.

  5. The Process of TiB2-Cu Composite Phase and Structure Formation during Combustion Synthesis

    Institute of Scientific and Technical Information of China (English)

    XU Qiang; ZHANG Xinghong; HAN Jiecai; PAN Wei


    The reaction process of combustion synthesis for TiB2- Cu was investigated in detail using combustion-wave arresting experiment, X-ray diffraction (XRD) analysis, SEM analysis and differential thermal analysis ( DTA ). The XRD analysis results for the different parts of the quenched specimen shaw that TiCux intermetallic phase firstly forms with the propagation of combustion wave, and then Ti1.87 B50 and Ti3 B4 metastable phases come forth due to the diffusion of B atoms and finally the stable TiB2 phase forms because of the continuous diffusion of B atoms. The formation of TiB2 phase is not completed by one step, but undergoes several transient processes. The process of reaction synthesis for Ti-B-Cu ternary system can be divided into three main stages: melting of Cu and Ti, and the formation of Cu- Ti melt and few TiCux , TiBx intermetallic phases; large numbers of TiCux intermetallic phases formation and some fine TiB2 particles precipitation; and the TiB2 particles coarsening and the stable TiB2 and Cu two phases formation in the final product.

  6. Mechanical and tribological characterization of TiB2 thin films. (United States)

    Silva, F J G; Casais, R C B; Martinho, R P; Baptista, A P M


    Titanium Diboride (TiB2) presents high mechanical and physical properties. Some wear studies were also carried out in order to evaluate its tribological properties. One of the most popular wear tests for thin films is the ball-cratering configuration. This work was focused on the study of the tribological properties of TiB2 thin films using micro-abrasion tests and following the BS EN 1071-6: 2007 standard. Due to high hardness usually patented by these films, diamond was selected as abrasive on micro-abrasion tests. Micro-abrasion wear tests were performed under five different durations, using the same normal load, speed rotation and ball. Films were deposited by unbalanced magnetron sputtering Physical Vapour Deposition (PVD) technique using TiB2 targets. TiB2 films were characterized using different methods as Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDS), Atomic Force Microscopy (AFM), X-ray Diffraction (XRD), Electron Probe Micro-Analyser (EPMA), Ultra Micro Hardness and Scratch-test Analysis, allowing to confirm that TiB2 presents adequate mechanical and physical properties. Ratio between hardness (coating and abrasive particles), wear resistance and wear coefficient were studied, showing that TiB2 films shows excellent properties for tribological applications.

  7. Fabrication and superconducting properties of nano-SiC doped MgB2 tapes

    Institute of Scientific and Technical Information of China (English)

    ZHANG XianPing; MA YanWei; GAO ZhaoShun; YU ZhengGuang; WANG DongLiang; WATANABE K; GUO JianDong


    Nano-SiC doped MgB2 tapes were prepared by the in situ powder-in-tube method. Heat treatment was performed at 650℃ for 1 h. XRD data indicate that SiC particles had reacted with the MgB2 during sintering process. MgB2 core seemed to be denser after SiC doping, and the critical temperature was slightly depressed. The critical current density Jc of the SiC doped tapes was significantly enhanced in magnetic fields up to 14 T compared to the undoped ones. For the 5% SiC doped samples, Jc was increased by a factor of 32 at 4.2 K, 10 T. The enhancement of Jc-B properties in SiC doped MgB2 tapes is considered to be due to the enhancement of grain linkages and the introduction of effective flux pining centers. The substitution of B by C in MgB2 grains is thought to be the main reason for the improvement of the flux pinning ability in SiC doped MgB2 tapes.

  8. Development of CYP11B1 and CYP11B2 assays utilizing homogenates of adrenal glands: Utility of monkey as a surrogate for human. (United States)

    Cerny, Matthew A; Csengery, Alexander; Schmenk, Jennifer; Frederick, Kosea


    Elevated levels of aldosterone are associated with arterial hypertension, congestive heart failure, chronic kidney disease, and obesity. Aldosterone is produced predominantly in the zona glomerulosa of the cortex of the adrenal gland by the enzyme aldosterone synthase (CYP11B2). Treatment of the above indications by decreasing production of aldosterone is thought to be of therapeutic benefit by lessening the deleterious effects of aldosterone mediated through both the mineralocorticoid receptor and also through so called non-