Sample records for b2 receptor ablation

  1. Regulation of bradykinin B2-receptor expression by oestrogen (United States)

    Madeddu, Paolo; Emanueli, Costanza; Varoni, Maria Vittoria; Demontis, Maria Piera; Anania, Vittorio; Gorioso, Nicola; Chao, Julie


    Tissue kallikrein is overexpressed in the kidney of female rats, this sexual dimorphism being associated with a greater effect of early blockade of bradykinin B2-receptors on female blood pressure phenotype. We evaluated the effect of ovariectomy and oestradiol benzoate (50 μg kg−1 every two days for two weeks) on the vasodepressor response to intra-arterial injection of bradykinin (150–900 ng kg−1) and on the expression of bradykinin B2-receptors.Ovariectomy reduced the magnitude of the vasodepressor response to bradykinin and unmasked a secondary vasopressor effect. Oestrogen replacement restored the vasodepressor response to bradykinin in ovariectomized rats.The vasodepressor responses to sodium nitroprusside (3–18 μg kg−1), acetylcholine (30–600 ng kg−1), desArg9-bradykinin (150–900 ng kg−1) or prostaglandin E2 (30–600 ng kg−1) were significantly reduced by ovariectomy. Oestrogen restored to normal the responses to desArg9-bradykinin, acetylcholine and prostaglandin E2, but not that to sodium nitroprusside.B2-receptor mRNA levels were decreased by ovariectomy in the aorta and kidney and they were restored to normal levels by oestrogen. Neither ovariectomy nor oestradiol affected receptor expression in the heart and uterus.These results indicate that oestrogen regulates B2-receptor gene expression and function. Since kinins exert a cardiovascular protective action, reduction in their vasodilator activity after menopause might contribute to the increased risk of pathological cardiovascular events. Conversely, the cardioprotective effects of oestrogen replacement might be, at least in part, mediated by activation of the kallikrein-kinin system. PMID:9283715

  2. Advanced Modelling and Functional Characterization of B2 Bradykinin Receptor

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    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.

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

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    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

  4. ErbB2 resembles an autoinhibited invertebrate epidermal growth factor receptor

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    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.

  5. 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...

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

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    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.

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

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    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.

  8. 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.

  9. Research resource: Comparative nuclear receptor atlas: basal and activated peritoneal B-1 and B-2 cells. (United States)

    Diehl, Cody J; Barish, Grant D; Downes, Michael; Chou, Meng-Yun; Heinz, Sven; Glass, Christopher K; Evans, Ronald M; Witztum, Joseph L


    Naïve murine B cells are typically divided into three subsets based on functional and phenotypic characteristics: innate-like B-1 and marginal zone B cells vs. adaptive B-2 cells, also known as follicular or conventional B cells. B-1 cells, the innate-immune-like component of the B cell lineage are the primary source of natural antibodies and have been shown to modulate autoimmune diseases, human B-cell leukemias, and inflammatory disorders such as atherosclerosis. On the other hand, B-2 cells are the principal mediators of the adaptive humoral immune response and represent an important pharmacological target for various conditions including rheumatoid arthritis, lupus erythematosus, and lymphomas. Using the resources of the Nuclear Receptor Signaling Atlas program, we used quantitative real-time PCR to assess the complement of the 49 murine nuclear receptor superfamily expressed in quiescent and toll-like receptor (TLR)-stimulated peritoneal B-1 and B-2 cells. We report the expression of 24 nuclear receptors in basal B-1 cells and 25 nuclear receptors in basal B-2 cells, with, in some cases, dramatic changes in response to TLR 4 or TLR 2/1 stimulation. Comparative nuclear receptor profiling between B-1 and peritoneal B-2 cells reveals a highly concordant expression pattern, albeit at quantitatively dissimilar levels. We also found that splenic B cells express 23 nuclear receptors. This catalog of nuclear receptor expression in B-1 and B-2 cells provides data to be used to better understand the specific roles of nuclear receptors in B cell function, chronic inflammation, and autoimmune disease.

  10. 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.

  11. 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.

  12. 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.

  13. 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. © 2016 Authors; published by Portland Press Limited.

  14. New insights into the stereochemical requirements of the bradykinin B2 receptor antagonists binding (United States)

    Lupala, Cecylia S.; Gomez-Gutierrez, Patricia; Perez, Juan J.


    Bradykinin (BK) is a member of the kinin family, released in response to inflammation, trauma, burns, shock, allergy and some cardiovascular diseases, provoking vasodilatation and increased vascular permeability among other effects. Their actions are mediated through at least two G-protein coupled receptors, B1 a receptor up-regulated during inflammation episodes or tissue trauma and B2 that is constitutively expressed in a variety of cell types. The goal of the present work is to carry out a structure-activity study of BK B2 antagonism, taking into account the stereochemical features of diverse non-peptide antagonists and the way these features translate into ligand anchoring points to complementary regions of the receptor, through the analysis of the respective ligand-receptor complex. For this purpose an atomistic model of the BK B2 receptor was built by homology modeling and subsequently refined embedded in a lipid bilayer by means of a 600 ns molecular dynamics trajectory. The average structure from the last hundred nanoseconds of the molecular dynamics trajectory was energy minimized and used as model of the receptor for docking studies. For this purpose, a set of compounds with antagonistic profile, covering maximal diversity were selected from the literature. Specifically, the set of compounds include Fasitibant, FR173657, Anatibant, WIN64338, Bradyzide, CHEMBL442294, and JSM10292. Molecules were docked into the BK B2 receptor model and the corresponding complexes analyzed to understand ligand-receptor interactions. The outcome of this study is summarized in a 3D pharmacophore that explains the observed structure-activity results and provides insight into the design of novel molecules with antagonistic profile. To prove the validity of the pharmacophore hypothesized a virtual screening process was also carried out. The pharmacophore was used as query to identify new hits using diverse databases of molecules. The results of this study revealed a set of new

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

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    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.

  16. 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

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

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    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...

  18. 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

  19. 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.

  20. 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.

  1. Pulmonary oedema producing toxin from Mesobuthus tamulus venom augments cardio-respiratory reflexes through B2 kinin receptors. (United States)

    Alex, Anitha B; Akella, Aparna; Tiwari, Anil K; Deshpande, Shripad B


    The current study was undertaken to compare the effects of pulmonary oedema producing toxin (PO-Tx) isolated from Mesobuthus tamulus venom on cardio-respiratory reflexes with exogenously administered bradykinin (BK) and to delineate the type of BK receptors mediating these responses. Jugular venous injection of phenyldiguanide (PDG) in anaesthetized rats produced reflex bradycardia, hypotension and apnoea. The PDG-induced reflex was augmented (two folds) by PO-Tx. The pulmonary water content in PO-Tx treated group was also increased. The PO-Tx-induced reflex changes as well as pulmonary oedema were blocked by-Hoe-140 implicating the involvement of B2 kinin receptors. Exogenous BK also produced augmentation (two folds) of the PDG-induced reflexes and increased the pulmonary water content. The BK-induced augmentation was blocked by pre-treatment with des-Arg10 Hoe 140 (a B1 receptor antagonist) and Hoe 140 (B2 receptor antagonist). However, these antagonists did not prevent the development of BK-induced pulmonary oedema. Present results indicate that PO-Tx augmented the PDG-induced reflex responses similar to BK and the PO-Tx induced augmentation of reflexes is mediated through B2 receptors.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. A single amino acid substitution is sufficient to modify the mitogenic properties of the epidermal growth factor receptor to resemble that of gp185erbB-2

    DEFF Research Database (Denmark)

    Di Fiore, P P; Helin, K; Kraus, M H


    The epidermal growth factor (EGF) receptor (EGFR) and the erbB-2 gene product, gp185erbB-2, exhibit distinct abilities to stimulate mitogenesis in different target cells. By using chimeric molecules between these two receptors, we have previously shown that their intracellular juxtamembrane regio...

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. B2-kinin receptors in the dorsal periaqueductal gray are implicated in the panicolytic-like effect of opiorphin. (United States)

    Sestile, Caio César; Maraschin, Jhonatan Christian; Rangel, Marcel Pereira; Santana, Rosangela Getirana; Zangrossi, Hélio; Graeff, Frederico Guilherme; Audi, Elisabeth Aparecida


    Reported results have shown that the pentapeptide opiorphin inhibits oligopeptidases that degrade brain neuropeptides, and has analgesic and antidepressant effects in experimental animals, without either tolerance or dependency after chronic administration. In a previous study we showed that opiorphin has a panicolytic-like effect in the dorsal periaqueductal gray (dPAG) electrical stimulation test (EST), mediated by the μ-opioid receptor (MOR). This study further analyzes the mechanism of opiorphin panicolytic action, using the EST and drug injection inside the dPAG. The obtained results showed that blockade of the 5-HT1A receptors with WAY-100635 did not change the escape-impairing effect of opiorphin, and combined injection of sub-effective doses of opiorphin and the 5-HT1A-agonist 8-OH-DPAT did not have a significant anti-escape effect. In contrast, the anti-escape effect of opiorphin was antagonized by pretreatment with the kinin B2 receptor blocker HOE-140, and association of sub-effective doses of opiorphin and bradykinin caused a significant anti-escape effect. The anti-escape effect of bradykinin was not affected by previous administration of WAY-100635. Therefore, the anti-escape effect of opiorphin in the dPAG seems to be mediated by endogenous bradykinin, acting on kinin B2 receptors, which previous results have shown to interact synergistically with MOR in the dPAG to restrain escape in two animal models of panic. Chemical compounds: Opiorphin (PubChem CID: 25195667); WAY100635 maleate salt (PubChem CID: 11957721); 8-OH-DPAT hydrobromide (PubChem CID: 6917794); Bradykinin (PubChem CID: 439201); HOE-140 (Icatibant) (PubChem CID: 6918173). Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Panicolytic-like action of bradykinin in the dorsal periaqueductal gray through μ-opioid and B2-kinin receptors. (United States)

    Sestile, Caio César; Maraschin, Jhonatan Christian; Gama, Vanessa Scalco; Zangrossi, Hélio; Graeff, Frederico Guilherme; Audi, Elisabeth Aparecida


    A wealth of evidence has shown that opioid and kinin systems may control proximal defense in the dorsal periaqueductal gray matter (dPAG), a critical panic-associated area. Studies with drugs that interfere with serotonin-mediated neurotransmission suggest that the μ-opioid receptor (MOR) synergistically interacts with the 5-HT1A receptor in the dPAG to inhibit escape, a panic-related behavior. A similar inhibitory effect has also been reported after local administration of bradykinin (BK), which is blocked by the non-selective opioid receptor antagonist naloxone. The latter evidence, points to an interaction between BK and opioids in the dPAG. We further explored the existence of this interaction through the dPAG electrical stimulation model of panic. We also investigated whether intra-dPAG injection of captopril, an inhibitor of the angiotensin-converting enzyme (ACE) that also degrades BK, causes a panicolytic-like effect. Our results showed that intra-dPAG injection of BK inhibited escape performance in a dose-dependent way, and this panicolytic-like effect was blocked by the BK type 2 receptor (B2R) antagonist HOE-140, and by the selective MOR antagonist CTOP. Conversely, the panicolytic-like effect caused by local administration of the selective MOR agonist DAMGO was antagonized by pre-treatment with either CTOP or HOE-140, indicating cross-antagonism between MOR and B2R. Finally, intra-dPAG injection of captopril also impaired escape in a dose-dependent way, and this panicolytic-like effect was blocked by pretreatment with HOE-140, suggesting mediation by endogenous BK. The panicolytic-like effect of captopril indicates that the use of ACE inhibitors in the clinical management of panic disorder may be worth exploring. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. High-temperature ablation behavior of TiB2-Cu matrix cermets%TiB2-Cu基金属陶瓷高温烧蚀行为研究

    Institute of Scientific and Technical Information of China (English)

    徐丽; 韩杰才; 张幸红; 徐强


    为研究TiB2-Cu基金属陶瓷材料的高温烧蚀行为,采用燃烧合成与同时致密化技术(SHS/PHIP)制备了TiB2-40Cu及TiB2-40Cu-8Ni金属陶瓷复合材料,利用电弧风洞试验考察了材料的抗热震和抗烧蚀性能,利用扫描电镜、电子探针及X射线衍射等方法对材料烧蚀前后的微观组织形貌及成分进行了检测.结果表明,试验模型表面均有烧蚀冲刷痕迹,TiB2-40Cu模型由于抗热震性较差,其表面有裂纹出现,TiB2-40Cu-8Ni的质量烧蚀率较TiB2-40Cu的质量烧蚀率低,微观组织分析表明,TiB2-40Cu模型烧蚀面中心区域剖面附近存在沿厚度方向100 μm左右的烧蚀区.TiB2-40Cu复合材料的烧蚀机理为金属相的熔化、化学烧蚀和机械剥蚀.

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    Bader Michael


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

  20. 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.

  1. 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...

  2. GRIP1 Binds to ApoER2 and EphrinB2 to Induce Activity-Dependent AMPA Receptor Insertion at the Synapse

    Directory of Open Access Journals (Sweden)

    Sylvia Pfennig


    Full Text Available Regulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA receptor trafficking in response to neuronal activity is critical for synaptic function and plasticity. Here, we show that neuronal activity induces the binding of ephrinB2 and ApoER2 receptors at the postsynapse to regulate de novo insertion of AMPA receptors. Mechanistically, the multi-PDZ adaptor glutamate-receptor-interacting protein 1 (GRIP1 binds ApoER2 and bridges a complex including ApoER2, ephrinB2, and AMPA receptors. Phosphorylation of ephrinB2 in a serine residue (Ser-9 is essential for the stability of such a complex. In vivo, a mutation on ephrinB2 Ser-9 in mice results in a complete disruption of the complex, absence of ApoER2 downstream signaling, and impaired activity-induced and ApoER2-mediated AMPA receptor insertion. Using compound genetics, we show the requirement of this complex for long-term potentiation (LTP. Together, our findings uncover a cooperative ephrinB2 and ApoER2 signaling at the synapse, which serves to modulate activity-dependent AMPA receptor dynamic changes during synaptic plasticity.

  3. 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.

  4. 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.

  5. 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.

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    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

  6. Androgen Receptor-Mediated Escape Mechanisms from Androgen Ablation Therapy (United States)


    of CAG repeats in the Machado-Joseph disease , spinocerebellar ataxia type 1 and androgen receptor genes. Hum. Mol. Genet. 4, 1585-1590. Rundlett, S . E... diseases such as Huntington disease and spinal and bulbar muscular atro- phy, which is commonly called Kennedy’s disease . This finding has been attributed...STATEMENT: Approved for Public Release; Distribution Unlimited The views, opinions and/or findings contained in this report are those of the author( s ) and

  7. 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.

  8. 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.

  9. 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

  10. 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.

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

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    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

  12. Ablation of NMDA receptors enhances the excitability of hippocampal CA3 neurons.

    Directory of Open Access Journals (Sweden)

    Fumiaki Fukushima

    Full Text Available Synchronized discharges in the hippocampal CA3 recurrent network are supposed to underlie network oscillations, memory formation and seizure generation. In the hippocampal CA3 network, NMDA receptors are abundant at the recurrent synapses but scarce at the mossy fiber synapses. We generated mutant mice in which NMDA receptors were abolished in hippocampal CA3 pyramidal neurons by postnatal day 14. The histological and cytological organizations of the hippocampal CA3 region were indistinguishable between control and mutant mice. We found that mutant mice lacking NMDA receptors selectively in CA3 pyramidal neurons became more susceptible to kainate-induced seizures. Consistently, mutant mice showed characteristic large EEG spikes associated with multiple unit activities (MUA, suggesting enhanced synchronous firing of CA3 neurons. The electrophysiological balance between fast excitatory and inhibitory synaptic transmission was comparable between control and mutant pyramidal neurons in the hippocampal CA3 region, while the NMDA receptor-slow AHP coupling was diminished in the mutant neurons. In the adult brain, inducible ablation of NMDA receptors in the hippocampal CA3 region by the viral expression vector for Cre recombinase also induced similar large EEG spikes. Furthermore, pharmacological blockade of CA3 NMDA receptors enhanced the susceptibility to kainate-induced seizures. These results raise an intriguing possibility that hippocampal CA3 NMDA receptors may suppress the excitability of the recurrent network as a whole in vivo by restricting synchronous firing of CA3 neurons.

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

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    Glen Daniel


    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

  14. Ablation of toll-like receptor 4 mitigates cardiac mitochondrial dysfunction in hyperhomocysteinemia. (United States)

    Jeremic, Nevena; Weber, Gregory J; Tyagi, Suresh C


    Hyperhomocysteinemia (HHcy) is a risk factor for adverse cardiovascular events; however, the mechanism for development of this disease is still unknown. Toll-like receptor 4 (TRL4) is a molecule involved in the immune response pathway and is quickly becoming a receptor of interest in the field of hypertension. In this study, we hypothesized that ablation of TLR4 mitigates cardiac mitochondrial dysfunction in a model of HHcy. Five strains of mice (C57BL/6J, CBS(+/-), C3H, CBS(+/-)/C3H, and C3H/HeOuJ) 10-12 weeks old were utilized. We found that HHcy causes heart hypertrophy and promotes oxidative stress while mice with HHcy and inactivated TLR4 showed significant improvement in examined parameters. A dominance of endothelial cell mitochondrial fission over mitochondrial fusion in HHcy and oxidative stress was observed, which may explain the endothelial cell loss and dysfunction that contributes to inward cardiac remodeling.

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

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    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

  16. 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...

  17. 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).

  18. The Effectiveness of Multiple Electrode Radiofrequency Ablation in Patients with Hepatocellular Carcinoma with Lesions More than 3 cm in Size and Barcelona Clinic Liver Cancer Stage A to B2 (United States)

    Lin, Chen-Chun; Cheng, Ya-Ting; Chen M, Wei-Ting; Lin, Shi-Ming


    Outcomes of hepatocellular carcinoma (HCC) lesions >3.0 cm in size including Barcelona Clinic Liver Cancer (BCLC) stage B after radiofrequency ablation (RFA) with a single electrode remain unsatisfactory. This study aimed to investigate the outcomes of RFA with multiple electrodes (ME-RFA) for HCC tumors 3.1-7.0 cm in size and BCLC stage B. This retrospective study included 70 consecutive patients with 58 medium- (3.1-5.0 cm) and 17 large- (5.1-7.0 cm) sized HCCs after ME-RFA using a controller. Outcomes in terms of complete response, primary technique effectiveness, local tumor progression, and overall survival were investigated. After 1-4 applications of ME-RFA, the rates of complete response and PTE in medium-sized tumors were 79.3% and 91.4%, respectively, and in large tumors were 76.5% and 94.1%, respectively. Overall, the major complication rate was 5.7%. After a median 21-month follow-up period, both two- and three-year estimated overall survival rates were above 80%. There were no significant differences in overall survival and local tumor progression rates between medium- and large-size tumors and among BCLC stages A, B1 and B2. A complete response to ME-RFA was the only significant factor associated with improved survival (p=0.008). In conclusion, ME-RFA can effectively treat 3.1-7.0-cm sized HCCs with a comparable outcome between medium- and large-size tumors and among BCLA stages A to B2. PMID:26989656

  19. 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.

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    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.

  20. β2-Adrenergic receptor ablation modulates hepatic lipid accumulation and glucose tolerance in aging mice. (United States)

    Shi, Yun; Shu, Zhen-Ju; Xue, Xiaoling; Yeh, Chih-Ko; Katz, Michael S; Kamat, Amrita


    Catecholamines acting through β-adrenergic receptors (β(1)-, β(2)-, β(3)-AR subtypes) modulate important biological responses in various tissues. Our previous studies suggest a role for increased hepatic β-AR-mediated signaling during aging as a mediator of hepatic steatosis, liver glucose output, and insulin resistance in rodents. In the current study, we have utilized β(2)-AR knockout (KO) and wildtype (WT) control mice to define further the role of β(2)-AR signaling during aging on lipid and glucose metabolism. Our results demonstrate for the first time that age-related increases in hepatic triglyceride accumulation and body weight are attenuated upon β(2)-AR ablation. Although no differences in plasma triglyceride, non-esterified fatty acids or insulin levels were detected between old WT and KO animals, an age-associated increase in hepatic expression of lipid homeostasis regulator Cidea was significantly reduced in old KO mice. Interestingly, we also observed a shift from reduced glucose tolerance in young adult KO animals to significantly improved glucose tolerance in old KO when compared to age-matched WT mice. These results provide evidence for an important role played by β(2)-ARs in the regulation of lipid and glucose metabolism during aging. The effect of β(2)-AR ablation on caloric intake during aging is currently not known and requires investigation. Future studies are also warranted to delineate the β(2)-AR-mediated mechanisms involved in the control of lipid and glucose homeostasis, especially in the context of a growing aging population. Published by Elsevier Inc.

  1. Excess of Aminopeptidase A in the Brain Elevates Blood Pressure via the Angiotensin II Type 1 and Bradykinin B2 Receptors without Dipsogenic Effect

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    Takuto Nakamura


    Full Text Available Aminopeptidase A (APA cleaves angiotensin (Ang II, kallidin, and other related peptides. In the brain, it activates the renin angiotensin system and causes hypertension. Limited data are available on the dipsogenic effect of APA and pressor effect of degraded peptides of APA such as bradykinin. Wistar-Kyoto rats received intracerebroventricular (icv APA in a conscious, unrestrained state after pretreatment with (i vehicle, (ii 80 μg of telmisartan, an Ang II type-1 (AT1 receptor blocker, (iii 800 nmol of amastatin, an aminopeptidase inhibitor, and (iv 1 nmol of HOE-140, a bradykinin B2 receptor blocker. Icv administration of 400 and 800 ng of APA increased blood pressure by 12.6 ± 3.0 and 19.0 ± 3.1 mmHg, respectively. APA did not evoke drinking behavior. Pressor response to APA was attenuated on pretreatment with telmisartan (vehicle: 22.1 ± 2.2 mmHg versus telmisartan: 10.4 ± 3.2 mmHg. Pressor response to APA was also attenuated with amastatin and HOE-140 (vehicle: 26.5 ± 1.1 mmHg, amastatin: 14.4 ± 4.2 mmHg, HOE-140: 16.4 ± 2.2 mmHg. In conclusion, APA increase in the brain evokes a pressor response via enzymatic activity without dipsogenic effect. AT1 receptors and B2 receptors in the brain may contribute to the APA-induced pressor response.

  2. Excess of Aminopeptidase A in the Brain Elevates Blood Pressure via the Angiotensin II Type 1 and Bradykinin B2 Receptors without Dipsogenic Effect (United States)

    Ishida, Akio; Ohya, Yusuke


    Aminopeptidase A (APA) cleaves angiotensin (Ang) II, kallidin, and other related peptides. In the brain, it activates the renin angiotensin system and causes hypertension. Limited data are available on the dipsogenic effect of APA and pressor effect of degraded peptides of APA such as bradykinin. Wistar-Kyoto rats received intracerebroventricular (icv) APA in a conscious, unrestrained state after pretreatment with (i) vehicle, (ii) 80 μg of telmisartan, an Ang II type-1 (AT1) receptor blocker, (iii) 800 nmol of amastatin, an aminopeptidase inhibitor, and (iv) 1 nmol of HOE-140, a bradykinin B2 receptor blocker. Icv administration of 400 and 800 ng of APA increased blood pressure by 12.6 ± 3.0 and 19.0 ± 3.1 mmHg, respectively. APA did not evoke drinking behavior. Pressor response to APA was attenuated on pretreatment with telmisartan (vehicle: 22.1 ± 2.2 mmHg versus telmisartan: 10.4 ± 3.2 mmHg). Pressor response to APA was also attenuated with amastatin and HOE-140 (vehicle: 26.5 ± 1.1 mmHg, amastatin: 14.4 ± 4.2 mmHg, HOE-140: 16.4 ± 2.2 mmHg). In conclusion, APA increase in the brain evokes a pressor response via enzymatic activity without dipsogenic effect. AT1 receptors and B2 receptors in the brain may contribute to the APA-induced pressor response. PMID:28421141

  3. Cloning and Expression of Ecdysone Receptor and Retinoid X Receptor from Procambarus clarkii: Induction by Eyestalk Ablation

    Directory of Open Access Journals (Sweden)

    Tian-Hao Dai


    Full Text Available Ecdysone receptor and retinoid X receptor are key regulators in molting. Here, full length ecdysone receptor (PcEcR and retinoid X receptor (PcRXR cDNAs from Procambarus clarkii were cloned. Full length cDNA of PcEcR has 2500 bp, encoding 576 amino acid proteins, and full length cDNA of PcRXR has 2593 bp, in which a 15 bp and a 204 bp insert/deletion splice variant regions in DNA binding domain and hinge domain were identified. The two splice variant regions in PcRXR result four isoforms: PcRXR1-4, encoding 525, 520, 457 and 452 amino acids respectively. PcEcR was highly expressed in the hepatopancreas and eyestalk and PcRXR was highly expressed in the eyestalk among eight examined tissues. Both PcEcR and PcRXR had induced expression after eyestalk ablation (ESA in the three examined tissues. In muscle, PcEcR and PcRXR were upregulated after ESA, PcEcR reached the highest level on day 3 after ESA and increased 33.5-fold relative to day 0, and PcRXR reached highest the level on day 1 after ESA and increased 2.7-fold relative to day 0. In the hepatopancreas, PcEcR and PcRXR dEcReased continuously after ESA, and the expression levels of PcEcR and PcRXR were only 0.7% and 1.7% on day 7 after ESA relative to day 0, respectively. In the ovaries, PcEcR was upregulated after ESA, reached the highest level on day 3 after ESA, increased 3.0-fold relative to day 0, and the expression level of PcRXR changed insignificantly after ESA (p > 0.05. The different responses of PcEcR and PcRXR after ESA indicates that different tissues play different roles (and coordinates their functions in molting.

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

    DEFF Research Database (Denmark)

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


    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...

  5. Lipodystrophy and severe metabolic dysfunction in mice with adipose tissue-specific insulin receptor ablation. (United States)

    Qiang, Guifen; Whang Kong, Hyerim; Xu, Shanshan; Pham, Hoai An; Parlee, Sebastian D; Burr, Aaron A; Gil, Victoria; Pang, Jingbo; Hughes, Amy; Gu, Xuejiang; Fantuzzi, Giamila; MacDougald, Ormond A; Liew, Chong Wee


    Insulin signaling plays pivotal roles in the development and metabolism of many tissues and cell types. A previous study demonstrated that ablation of insulin receptor (IR) with aP2-Cre markedly reduced adipose tissues mass and protected mice from obesity. However, multiple studies have demonstrated widespread non-adipocyte recombination of floxed alleles in aP2-Cre mice. These findings underscore the need to re-evaluate the role of IR in adipocyte and systemic metabolism with a more adipose tissue-specific Cre mouse line. We generated and phenotyped a new adipose tissue-specific IR mouse model using the adipose tissue-specific Adipoq-Cre line. Here we show that the Adipoq-Cre-mediated IR KO in mice leads to lipodystrophy and metabolic dysfunction, which is in stark contrast to the previous study. In contrast to white adipocytes, absence of insulin signaling does not affect development of marrow and brown adipocytes, but instead is required for lipid accumulation particularly for the marrow adipocytes. Lipodystrophic IR KO mice have profound insulin resistance, hyperglycemia, organomegaly, and impaired adipokine secretion. Our results demonstrate differential roles for insulin signaling for white, brown, and marrow adipocyte development and metabolic regulation.

  6. Ablations of ghrelin and ghrelin receptor exhibit differential metabolic phenotypes and thermogenic capacity during aging.

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    Xiaojun Ma

    Full Text Available BACKGROUND: Obesity is a hallmark of aging in many Western societies, and is a precursor to numerous serious age-related diseases. Ghrelin (Ghrl, via its receptor (growth hormone secretagogue receptor, GHS-R, is shown to stimulate GH secretion and appetite. Surprisingly, our previous studies showed that Ghrl(-/- mice have impaired thermoregulatory responses to cold and fasting stresses, while Ghsr(-/- mice are adaptive. METHODOLOGY/PRINCIPAL FINDINGS: To elucidate the mechanism, we analyzed the complete metabolic profiles of younger (3-4 months and older (10-12 months Ghrl(-/- and Ghsr(-/- mice. Food intake and locomotor activity were comparable for both null mice and their wild-type (WT counterparts, regardless of age. There was also no difference in body composition between younger null mice and their WT counterparts. As the WT mice aged, as expected, the fat/lean ratio increased and energy expenditure (EE decreased. Remarkably, however, older Ghsr(-/- mice exhibited reduced fat/lean ratio and increased EE when compared to older WT mice, thus retaining a youthful lean and high EE phenotype; in comparison, there was no significant difference with EE in Ghrl(-/- mice. In line with the EE data, the thermogenic regulator, uncoupling protein 1 (UCP1, was significantly up-regulated in brown adipose tissue (BAT of Ghsr(-/- mice, but not in Ghrl(-/- mice. CONCLUSIONS: Our data therefore suggest that GHS-R ablation activates adaptive thermogenic function(s in BAT and increases EE, thereby enabling the retention of a lean phenotype. This is the first direct evidence that the ghrelin signaling pathway regulates fat-burning BAT to affect energy balance during aging. This regulation is likely mediated through an as-yet-unidentified new ligand of GHS-R.

  7. Phenotype of mice with inducible ablation of GluA1 AMPA receptors during late adolescence: relevance for mental disorders. (United States)

    Inta, Dragos; Vogt, Miriam A; Elkin, Hasan; Weber, Tillmann; Lima-Ojeda, Juan M; Schneider, Miriam; Luoni, Alessia; Riva, Marco A; Gertz, Karen; Hellmann-Regen, Julian; Kronenberg, Golo; Meyer-Lindenberg, Andreas; Sprengel, Rolf; Gass, Peter


    Adolescence is characterized by important molecular and anatomical changes with relevance for the maturation of brain circuitry and cognitive function. This time period is of critical importance in the emergence of several neuropsychiatric disorders accompanied by cognitive impairment, such as affective disorders and schizophrenia. The molecular mechanisms underlying these changes at neuronal level during this specific developmental stage remains however poorly understood. GluA1-containing AMPA receptors, which are located predominantly on hippocampal neurons, are the primary molecular determinants of synaptic plasticity. We investigated here the consequences of the inducible deletion of GluA1 AMPA receptors in glutamatergic neurons during late adolescence. We generated mutant mice with a tamoxifen-inducible deletion of GluA1 under the control of the CamKII promoter for temporally and spatially restricted gene manipulation. GluA1 ablation during late adolescence induced cognitive impairments, but also marked hyperlocomotion and sensorimotor gating deficits. Unlike the global genetic deletion of GluA1, inducible GluA1 ablation during late adolescence resulted in normal sociability. Deletion of GluA1 induced redistribution of GluA2 subunits, suggesting AMPA receptor trafficking deficits. Mutant animals showed increased hippocampal NMDA receptor expression and no change in striatal dopamine concentration. Our data provide new insight into the role of deficient AMPA receptors specifically during late adolescence in inducing several cognitive and behavioral alterations with possible relevance for neuropsychiatric disorders.

  8. 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.

  9. Ablation of ghrelin receptor in leptin-deficient ob/ob mice has paradoxical effects on glucose homeostasis when compared with ablation of ghrelin in ob/ob mice (United States)

    The orexigenic hormone ghrelin is important in diabetes because it has an inhibitory effect on insulin secretion. Ghrelin ablation in leptin-deficient ob/ob (Ghrelin(-/-):ob/ob) mice increases insulin secretion and improves hyperglycemia. The physiologically relevant ghrelin receptor is the growth ...

  10. 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.

  11. Local delivery of a selective androgen receptor modulator failed as an anabolic agent in a rat bone marrow ablation model. (United States)

    Aro, Hannu T; Kulkova, Julia; Moritz, Niko; Kähkönen, Esa; Mattila, Riina H


    Selective androgen receptor modulators (SARMs) have been developed to have systemic anabolic effects on bones and muscles without the adverse effects of steroidal androgens. One unexplored therapeutic option is the targeted application of SARMs for the enhancement of local new bone formation. We evaluated the osteogenic efficacy of a locally released SARM (ORM-11984). ORM-11984 was mixed with a copolymer of L-lactide and ɛ-caprolactone (PLCL). An in vitro dissolution test confirmed the sustainable release of ORM-11984 from the matrix. A bone marrow ablation model was used in female Sprague-Dawley rats. Implants containing 10%, 30%, or 50% ORM-11984 by weight or pure PLCL were inserted into the medullary canal of the ablated tibia. At 6 and 12 weeks, the volume of intramedullary new bone and the perimeter of bone-implant contact were measured by micro-computed tomography and histomorphometry. Contrary to our hypothesis, there was a negative correlation between the amount of new bone around the implant and the dose of ORM-11984. There was only a mild (and not statistically significant) enhancement of bone formation in ablated bones subjected to the lowest dose of the SARM (10%). This study suggests that intramedullary/endosteal osteogenesis had a negative, dose-dependent response to locally released SARM. This result highlights the complexity of androgenic effects on bones and also suggests that there are biological limits to the targeted local application of SARMs.

  12. Toll-like receptor 4 ablation rescues against paraquat-triggered myocardial dysfunction: Role of ER stress and apoptosis. (United States)

    Lei, Yonghong; Li, Xue; Yuan, Fang; Liu, Lu; Zhang, Juan; Yang, Yanping; Zhao, Jieqiong; Han, Yan; Ren, Jun; Fu, Xiaobing


    Paraquat is a nitrogen herbicide imposing severe organ toxicity in human leading to acute lung injury and heart failure. The present study was designed to examine the impact of ablation of the innate proinflammatory mediator toll-like receptor 4 (TLR4) in paraquat-induced cardiac contractile dysfunction and the underlying mechanisms involved with a focus on endoplasmic reticulum (ER) stress and apoptosis. Adult male wild-type (WT) and TLR4 knockout (TLR4(-/-) ) mice were challenged with paraquat (45 mg/kg, i.p.) for 48 h prior to the assessment of myocardial and cardiomyocyte sarcomere function, ER stress, apoptosis and inflammation. Acute paraquat challenge exerted myocardial functional and geometric alterations including enlarged left ventricular end systolic diameter (LVESD), reduced fractional shortening, decreased sarcomere shortening, maximal velocities of sarcomere shortening and relengthening associated with unchanged LV posterior wall thickness, septal thickness, LV end diastolic diameter (LVEDD), heart rate, sarcomere length, time-to-peak shortening and time-to-90% relengthening. Although TLR4 ablation did not affect mechanical properties in the heart, it significantly attenuated or ablated paraquat-induced cardiac contractile anomalies. Moreover, paraquat imposed overt ER stress, apoptosis and inflammation as evidenced by upregulation of Bip, CHOP, Caspase-3, -9, Bax, Bad, and IL-1β, phosphorylation of PERK, eIF2α and IΚB, as well as activation of the stress molecules ERK and p38, with unchanged Caspase-8, Bcl2, TNF-α, p53, HMGB1, MyD88 and phosphorylation of Akt, GSK3β and JNK, the effects of which were attenuated or negated by TLR4 knockout. Taken together, our results suggested that TLR4 ablation alleviated paraquat-induced myocardial contractile dysfunction possibly through attenuation of ER stress, apoptosis and inflammation. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 656-668, 2017.

  13. 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...

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

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    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.

  15. Endothelin Receptor B2 (EDNRB2) Is Responsible for the Tyrosinase-Independent Recessive White (mow) and Mottled (mo) Plumage Phenotypes in the Chicken (United States)

    Kinoshita, Keiji; Akiyama, Toyoko; Mizutani, Makoto; Shinomiya, Ai; Ishikawa, Akira; Younis, Hassan Hassan; Tsudzuki, Masaoki; Namikawa, Takao; Matsuda, Yoichi


    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 mow for this mutant allele. Furthermore, the F1 hybrid between the mow/mow chicken and the panda (s/s) mutant of Japanese quail (Coturnix japonica), whose causative gene is the endothelin receptor B2 (EDNRB2) gene, showed a mow/mow 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. PMID:24466053

  16. 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

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    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

  17. 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.

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

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    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.

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

  20. Protective role of tumor necrosis factor (TNF) receptors in chronic intestinal inflammation: TNFR1 ablation boosts systemic inflammatory response. (United States)

    Wang, Yi; Han, Gencheng; Chen, Yu; Wang, Ke; Liu, Guijun; Wang, Renxi; Xiao, He; Li, Xinying; Hou, Chunmei; Shen, Beifen; Guo, Renfeng; Li, Yan; Chen, Guojiang


    Tumor necrosis factor-α (TNF-α) acts as a key factor for the development of inflammatory bowel diseases (IBDs), whose function is known to be mediated by TNF receptor 1 (TNFR1) or TNFR2. However, the precise role of the two receptors in IBD remains poorly understood. Herein, chronic colitis was established by oral administration of dextran sulfate sodium (DSS) in TNFR1 or TNFR2-/- mice. Unexpectedly, TNFR1 or TNFR2 deficiency led to exacerbation of signs of colitis compared with wild-type (WT) counterparts. Of note, TNFR1 ablation rendered significantly increased mortality compared with TNFR2 and WT mice after DSS. Aggravated pathology of colitis in TNFR1-/- or TNFR2-/- mice correlated with elevated colonic expression of proinflammatory cytokines and chemokines. Importantly, ablation of TNFR1 or TNFR2 increased apoptosis of colonic epithelial cells, which might be due to the heightened ratio of Bax/Bcl-2 and increased expression of caspase-8. Intriguingly, despite comparable intensity of intestinal inflammation in TNFR-deficient mice after DSS, systemic inflammatory response (including splenomegaly and myeloid expansion) was augmented dramatically in TNFR1-/- mice, instead of TNFR2-/- mice. Granulocyte-macrophage colony-stimulating factor (GMCSF) was identified as a key mediator in this process, as neutralization of GMCSF dampened peripheral inflammatory reaction and reduced mortality in TNFR1-/- mice. These data suggest that signaling via TNFR1 or TNFR2 has a protective role in chronic intestinal inflammation, and that lacking TNFR1 augments systemic inflammatory response in GMCSF-dependent manner.

  1. 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...

  2. 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

  3. 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...

  4. Mecanismos envolvidos no efeito modulatório de citocinas pró-inflamatórias sobre as respostas mediadas pelos receptores B1 e B2 para as cininas na pata de rato.


    Campos, Maria Martha


    Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências Biológicas. Programa de Pós-Graduação em Farmacologia. Estudo do efeito do tratamento local com [citocinas pró-inflamatórias] sobre as respostas mediadas pelos [receptores B1 e B2] para as [cininas] na [pata de rato]. O tratamento com as citocinas [IL-1b] ou [TNFa] foi capaz de induzir um aumento dose-dependente e marcante da [resposta edematogênica] mediada pelos receptores B1, acompanhado de um aumento na [expr...

  5. 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.

  6. 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

  7. Ablation of NK1 Receptors in Rat Nucleus Tractus Solitarii Blocks Baroreflexes

    National Research Council Canada - National Science Library

    Riley, Jeffrey; Lin, Li-Hsien; Chianca, Jr, Deoclecio A; Talman, William T


    .... The neurokinin-1 receptors at which SP may act have been identified in the nucleus tractus solitarii, but there remains uncertainty if the neurons at which SP acts are critical to baroreflex transmission...

  8. 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

  9. 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.

  10. 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...

  11. 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.

  12. TiC-TiB2/Cu复合材料的抗热震及抗烧蚀行为研究%Study on the behavior in thermal shock and ablation resistance of TiC-TiB2/Cu ceramic-matrix composite

    Institute of Scientific and Technical Information of China (English)

    朱春城; 李垚; 赫晓东; 张幸红; 韩杰才



  13. 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...

  14. 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

  15. 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. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Predictive value of pre-procedural autoantibodies against M2-muscarinic acetylcholine receptor for recurrence of atrial fibrillation one year after radiofrequency catheter ablation

    Directory of Open Access Journals (Sweden)

    Zou Changhong


    Full Text Available Abstract Background Increasing evidences have suggested that autoantibodies against muscarinic-2 acetylcholine receptor (anti-M2-R may play an important role in the development of atrial fibrillation (AF. Predictive value of pre-procedural anti-M2-R for the recurrence of AF after radiofrequency catheter ablation is still unclear. Methods Totally 76 AF patients with preserved left ventricular systolic function were prospectively enrolled and subjected to ablation after the detection of serum anti-M2-R by enzyme linked immunosorbent assay. These patients were given follow-up examination for one year after ablation. Risk estimation for the recurrence of AF was performed using the univariate and multivariate logistic regression. Results In AF group, serum anti-M2-R was significantly higher than that in the control group in terms of frequency (40.8% versus 11.7%; p p p = 0.009 and titer (1:132 versus 1:94; p = 0.012 for autoantibodies. During one-year follow-up examination after ablation, the recurrence of AF was observed in 25 (32.9% patients. Multivariate analysis showed that pre-procedural serum anti-M2-R was an independent predictor for the recurrence of AF at the time point of 12 months after ablation (odds ratio: 4.701; 95% confidence interval: 1.590-13.894; p = 0.005. Conclusions In AF patients, the frequency and titer of serum anti-M2-R were significantly higher than those in the control group with sinus rhythm. Pre-procedural serum anti-M2-R was an independent predictor for the recurrence of AF one year after radiofrequency catheter ablation.

  17. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers have no beneficial effect on ablation outcome in chronic persistent atrial fibrillation. (United States)

    Zheng, Bin; Kang, Junping; Tian, Ying; Tang, Ribo; Long, Deyong; Yu, Ronghui; He, Hua; Zhang, Ming; Shi, Lisheng; Tao, Hailong; Liu, Xingpeng; Dong, Jianzeng; Ma, Changsheng


    Previous studies have shown that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) could reverse structural and electrical atria remodelling and decrease atrial fibrillation (AF) onset or recurrence. The aim of this retrospective study was to investigate whether ACEIs/ARBs had beneficial effects on ablation outcome of chronic persistent AF. This study included 139 patients with chronic persistent AF who underwent radiofrequency ablation in our centre. Patients were divided into an ACEIs/ARBs group or a non-ACEIs/ARBs group. During follow-up (14.6 +/- 8.9 months) after AF ablation, AF-free survival in the ACEIs/ARBs group was not significantly different from the non-ACEIs/ARBs group (P = 0.339). Univariate analysis showed that predictors for AF-free survival were AF history (HR, 1.064; 95% CI, 1.021-1.108; P = 0.003) and duration of chronic persistent AF (HR, 1.012; 95% CI, 1.005-1.019; P = 0.001). Multivariate analysis showed that predictors for AF-free survival were AF history (HR, 1.051; 95% CI, 1.004-1.101; P = 0.035) and duration of chronic persistent AF (HR, 1.012; 95% CI, 1.004-1.020; P = 0.004). ACEIs/ARBs therapy was not a predictor for AF-free survival neither in univariate nor multivariate analysis. In this observational study, no effect of ACEIs or ARBs was seen on the AF recurrence after ablation of chronic persistent AF.ACEIs/ARBs did not help to predict a better ablation outcome. Predictors for ablation outcome are AF history and duration of chronic persistent AF.

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

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    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. 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.

  20. Ablation of ghrelin receptor reduces adiposity and improves insulin sensitivity during aging by regulating fat metabolism in white and brown adipose tissues. (United States)

    Lin, Ligen; Saha, Pradip K; Ma, Xiaojun; Henshaw, Iyabo O; Shao, Longjiang; Chang, Benny H J; Buras, Eric D; Tong, Qiang; Chan, Lawrence; McGuinness, Owen P; Sun, Yuxiang


    Aging is associated with increased adiposity in white adipose tissues and impaired thermogenesis in brown adipose tissues; both contribute to increased incidences of obesity and type 2 diabetes. Ghrelin is the only known circulating orexigenic hormone that promotes adiposity. In this study, we show that ablation of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R) improves insulin sensitivity during aging. Compared to wild-type (WT) mice, old Ghsr(-/-) mice have reduced fat and preserve a healthier lipid profile. Old Ghsr(-/-) mice also exhibit elevated energy expenditure and resting metabolic rate, yet have similar food intake and locomotor activity. While GHS-R expression in white and brown adipose tissues was below the detectable level in the young mice, GHS-R expression was readily detectable in visceral white fat and interscapular brown fat of the old mice. Gene expression profiles reveal that Ghsr ablation reduced glucose/lipid uptake and lipogenesis in white adipose tissues but increased thermogenic capacity in brown adipose tissues. Ghsr ablation prevents age-associated decline in thermogenic gene expression of uncoupling protein 1 (UCP1). Cell culture studies in brown adipocytes further demonstrate that ghrelin suppresses the expression of adipogenic and thermogenic genes, while GHS-R antagonist abolishes ghrelin's effects and increases UCP1 expression. Hence, GHS-R plays an important role in thermogenic impairment during aging. Ghsr ablation improves aging-associated obesity and insulin resistance by reducing adiposity and increasing thermogenesis. Growth hormone secretagogue receptor antagonists may be a new means of combating obesity by shifting the energy balance from obesogenesis to thermogenesis. © 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.

  1. 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.

  2. Genetic ablation of NMDA receptor subunit NR3B in mouse reveals motoneuronal and nonmotoneuronal phenotypes. (United States)

    Niemann, Stephan; Kanki, Hiroaki; Fukui, Yasuyuki; Takao, Keizo; Fukaya, Masahiro; Hynynen, Meri N; Churchill, Michael J; Shefner, Jeremy M; Bronson, Roderick T; Brown, Robert H; Watanabe, Masahiko; Miyakawa, Tsuyoshi; Itohara, Shigeyoshi; Hayashi, Yasunori


    NR3B is a modulatory subunit of the NMDA receptor, abundantly expressed in both cranial and spinal somatic motoneurons and at lower levels in other regions of the brain as well. Recently, we found the human NR3B gene (GRIN3B) to be highly genetically heterogeneous, and that approximately 10% of the normal European-American population lacks NR3B due to homozygous occurrence of a null allele in the gene. Therefore, it is especially important to understand the phenotypic consequences of the genetic loss of NR3B in both humans and animal models. We here provide results of behavioral analysis of mice genetically lacking NR3B, which is an ideal animal model due to homogeneity in genetic and environmental background. The NR3B(-/-) mice are viable and fertile. Consistent with the expression of NR3B in somatic motoneurons, the NR3B(-/-) mice showed a moderate but significant impairment in motor learning or coordination, and decreased activity in their home cages. Remarkably, the NR3B(-/-) mice showed a highly increased social interaction with their familiar cage mates in their home cage but moderately increased anxiety-like behaviour and decreased social interaction in a novel environment, consistent with the inhibitory role of NR3B on the functions of NMDA receptors. This work is the first reporting of the functional significance of NR3B in vivo and may give insight into the contribution of genetic variability of NR3B in the phenotypic heterogeneity among human population.

  3. 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

  4. Defining BMP functions in the hair follicle by conditional ablation of BMP receptor IA. (United States)

    Kobielak, Krzysztof; Pasolli, H Amalia; Alonso, Laura; Polak, Lisa; Fuchs, Elaine


    Using conditional gene targeting in mice, we show that BMP receptor IA is essential for the differentiation of progenitor cells of the inner root sheath and hair shaft. Without BMPRIA activation, GATA-3 is down-regulated and its regulated control of IRS differentiation is compromised. In contrast, Lef1 is up-regulated, but its regulated control of hair differentiation is still blocked, and BMPRIA-null follicles fail to activate Lef1/beta-catenin-regulated genes, including keratin genes. Wnt-mediated transcriptional activation can be restored by transfecting BMPRIA-null keratinocytes with a constitutively activated beta-catenin. This places the block downstream from Lef1 expression but upstream from beta-catenin stabilization. Because mice lacking the BMP inhibitor Noggin fail to express Lef1, our findings support a model, whereby a sequential inhibition and then activation of BMPRIA is necessary to define a band of hair progenitor cells, which possess enough Lef1 and stabilized beta-catenin to activate the hair specific keratin genes and generate the hair shaft.

  5. Physiopathology of dental rickets in vitamin D receptor-ablated mice. (United States)

    Descroix, V; Kato, S; Lézot, F; Berdal, A


    1α25(OH)(2)vitaminD(3) and its nuclear receptor, VDR, are essential for normal tooth development. However, the relative contributions of the direct vs. indirect effects of vitamin D action on odontogenesis are unclear. The aim of this study was to discriminate among the specific roles of 1α25(OH)(2) vitaminD(3), calcemia/phosphatemia, and the maternal environment in mouse VDR null mutants. Microradiographic, histological, and molecular analyses were conducted on adult mice under hypocalcemic/hypophosphatemic vs. normocalcemic/normophosphatemic conditions, and pups of first- (VDR-/- born to VDR+/- dams) vs. second-generation (VDR-/- born to VDR-/- dams) mice. In VDR-/- mice, crown morphogenesis was affected exclusively in second-generation pups. In first-generation adult VDR-/- mice, both enamel and dentin were affected, and pathologic features of root resorption in both apical and cervical regions were observed. Nutritional calcium and phosphate normalization completely rescued the root resorption and partially rescued the dentin and enamel phenotypes (altered cell differentiation and matrix protein expression). Analysis of these data illustrates the co-existence of different pathways of vitamin D action in tooth differentiation and biomineralization. These targeted and cumulative effects would generate the diverse and wide spectrum of dental rickets phenotypes.

  6. Targeted ablation of the PTH/PTHrP receptor in osteocytes impairs bone structure and homeostatic calcemic responses. (United States)

    Powell, William F; Barry, Kevin J; Tulum, Irena; Kobayashi, Tatsuya; Harris, Stephen E; Bringhurst, F Richard; Pajevic, Paola Divieti


    Parathyroid hormone (PTH) is a major physiologic regulator of calcium, phosphorous, and skeletal homeostasis. Cells of the osteoblastic lineage are key targets of PTH action in bone, and recent evidence suggests that osteocytes might be important in the anabolic effects of PTH. To understand the role of PTH signaling through the PTH/PTHrP receptors (PPR) in osteocytes and to determine the role(s) of these cells in mediating the effects of the hormone, we have generated mice in which PPR expression is specifically ablated in osteocytes. Transgenic mice in which the 10 kb-Dmp1 promoter drives a tamoxifen-inducible Cre-recombinase were mated with animals in which exon 1 of PPR is flanked by lox-P sites. In these animals, osteocyte-selective PPR knockout (Ocy-PPR(cKO) mice) could be induced by administration of tamoxifen. Histological analysis revealed a reduction in trabecular bone and mild osteopenia in Ocy-PPR(cKO) mice. Reduction of trabeculae number and thickness was also detected by micro-computed tomography analysis whereas bone volume fraction (BV/TV%) was unchanged. These findings were associated with an increase in Sost and sclerostin expression. When Ocy-PPR(cKO) mice were subjected to a low-calcium diet to induce secondary hyperparathyroidism, their blood calcium levels were significantly lower than littermate controls. Moreover, PTH was unable to suppress Sost and sclerostin expression in the Ocy-PPR(cKO) animals, suggesting an important role of PTH signaling in osteocytes for proper bone remodeling and calcium homeostasis.

  7. Selective ablation of the androgen receptor in mouse sertoli cells affects sertoli cell maturation, barrier formation and cytoskeletal development.

    Directory of Open Access Journals (Sweden)

    Ariane Willems

    Full Text Available The observation that mice with a selective ablation of the androgen receptor (AR in Sertoli cells (SC (SCARKO mice display a complete block in meiosis supports the contention that SC play a pivotal role in the control of germ cell development by androgens. To delineate the physiological and molecular mechanism responsible for this control, we compared tubular development in pubertal SCARKO mice and littermate controls. Particular attention was paid to differences in SC maturation, SC barrier formation and cytoskeletal organization and to the molecular mediators potentially involved. Functional analysis of SC barrier development by hypertonic perfusion and lanthanum permeation techniques and immunohistochemical analysis of junction formation showed that SCARKO mice still attempt to produce a barrier separating basal and adluminal compartment but that barrier formation is delayed and defective. Defective barrier formation was accompanied by disturbances in SC nuclear maturation (immature shape, absence of prominent, tripartite nucleoli and SC polarization (aberrant positioning of SC nuclei and cytoskeletal elements such as vimentin. Quantitative RT-PCR was used to study the transcript levels of genes potentially related to the described phenomena between day 8 and 35. Differences in the expression of SC genes known to play a role in junction formation could be shown from day 8 for Cldn11, from day 15 for Cldn3 and Espn, from day 20 for Cdh2 and Jam3 and from day 35 for ZO-1. Marked differences were also noted in the transcript levels of several genes that are also related to cell adhesion and cytoskeletal dynamics but that have not yet been studied in SC (Actn3, Ank3, Anxa9, Scin, Emb, Mpzl2. It is concluded that absence of a functional AR in SC impedes the remodeling of testicular tubules expected at the onset of spermatogenesis and interferes with the creation of the specific environment needed for germ cell development.

  8. 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...

  9. 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.

  10. 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.

  11. 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.

  12. Catheter Ablation (United States)

    ... ablation. Visit Cardiac ablation procedures and Cardiac conduction system for more information about this topic. Related ... National Institutes of Health Department of Health and Human Services

  13. ErbB-2 blockade and prenyltransferase inhibition alter epidermal growth factor and epidermal growth factor receptor trafficking and enhance (111)In-DTPA-hEGF Auger electron radiation therapy. (United States)

    Cornelissen, Bart; Darbar, Sonali; Hernandez, Rebecca; Kersemans, Veerle; Tullis, Iain; Barber, Paul R; Smart, Sean; Vojnovic, Borivoj; Reilly, Raymond; Vallis, Katherine A


    The intracellular distribution of Auger electron-emitting radiopharmaceuticals is a determinant of cytotoxicity. However, the mechanisms by which these agents are routed through the cell are ill understood. The aim of this study was to investigate how trafficking of (111)In-labeled human epidermal growth factor ((111)In-DTPA-hEGF) relates to that of the EGF receptor (EGFR) and whether coadministration of agents that modulate EGFR signaling alters the efficacy of (111)In-DTPA-hEGF. The spatiotemporal interaction between AlexaFluor488-EGF (AF488-EGF) and Cy3-conjugated anti-EGFR antibody (Cy3-anti-EGFR) was studied in the breast cancer cell line MDA-MB-468 using fluorescence resonance energy transfer and 2-photon fluorescence lifetime imaging. (111)In internalization and nuclear fractionation assays were performed to investigate the effect of the ErbB-2-blocking antibody trastuzumab and a prenyltransferase inhibitor, L-778,123, on the subcellular localization of (111)In-DTPA-hEGF in MDA-MB-468 (1.3 × 10(6) EGFR per cell; ErbB-2 negative) and 231-H2N (0.2 × 10(6) EGFR per cell; 0.4 × 10(5) ErbB-2 per cell) cell lines. The cytotoxicity of (111)In-DTPA-hEGF (0-64 nM) plus trastuzumab (0-50 μg/mL) or L-778,123 (0-22.5 μM) was measured using clonogenic assays in a panel of breast cancer cell lines that express different levels of EGFR and ErB-2. Clonogenic survival data were used to calculate combination indices. Tumor growth inhibition was measured in vivo in 231-H2N xenograft-bearing mice treated with (111)In-DTPA-hEGF plus trastuzumab or L-788,123. Using fluorescence resonance energy transfer, we showed that EGF interacts with EGFR in the cytoplasm and nucleus after internalization of the ligand-receptor complex in MDA-MB-468 cells. Nuclear localization of (111)In-DTPA-hEGF is enhanced by trastuzumab and L-788,123. Trastuzumab and L-788,123 sensitized 231-H2N cells to (111)In-DTPA-hEGF. Nuclear localization and cytotoxicity of (111)In-DTPA-hEGF were significantly

  14. Influence of specific and non-specific endothelin receptor antagonists on renal morphology in rats with surgical renal ablation. (United States)

    Nabokov, A; Amann, K; Wagner, J; Gehlen, F; Münter, K; Ritz, E


    Studies in experimental models of chronic renal failure suggest an important role for the endothelin system in the development of renal scarring. Endothelin receptor (ETR) anatagonists interfere with progression, but it has not been resolved (i) whether this is true for all models of renal damage, (ii) to what extent the effect is modulated by systemic blood pressure and (iii) whether the effect is similar for ETAR and ETA/ETBR antagonists. 5/6 subtotal nephrectomy (SNX) by surgical ablation in male Sprague-Dawley rats. Comparison of ACE inhibitor Trandolapril (0.1 mg/kg/day), ETAR antagonist BMS 182874 (30 mg/kg/day) and ETAR/ETBR antagonist Ro 46-2005 (30 mg/kg/day) by gavage. Duration of the experiment eight weeks. Systolic blood pressure by tail plethysmography. Perfusion fixation of kidneys and morphometric analysis ET-1 and ETA/ETBR by quantitative PCR. SNX caused a significant (P < 0.01) increase of systolic blood pressure (170 +/- 8.6 mmHg) compared to sham operated controls (131 +/- 5.3 mmHg). Blood pressure was significantly (P < 0.001) lower with Trandolapril (128 +/- 5.3 mmHg), but not with BMS 182874 (153 +/- 5.9 mmHg) or Ro 46-2005 (167 +/- 7.6 mmHg). Compared to sham operated rats (0.03 +/- 0.01) glomerulosclerosis index (GSI) was significantly (P < 0.01) higher in the untreated SNX group (0.9 +/- 0.15). Significantly lower GSI was found in Trandolapril treated (0.29 +/- 0.04), BMS 182874 treated (0.36 +/- 0.05), and Ro 46-2005 treated animals (0.45 +/- 0.11). The effect of BMS 182874 was accompanied by lower tubulointerstitial damage index. Mean glomerular volume was dramatically increased (P < 0.001) in SNX rats as compared to sham operated animals. This glomerular enlargement was partially prevented by Trandolapril (P < 0.05), but not by either ETR antagonist. ET-1 mRNA tended to be higher in SNX irrespective of treatment, while ETAR and ETBR mRNA were significantly lower. Both specific (ETAR) and non-specific (ETA/ETBR) endothelin antagonists

  15. Involvement of bradykinin B2 and muscarinic receptors in the prolonged diuretic and antihypertensive properties of Echinodorus grandiflorus (Cham. & Schltdl.) Micheli. (United States)

    Prando, Thiago Buno Lima; Barboza, Lorena Neris; Araújo, Valdinei de Oliveira; Gasparotto, Francielly Mourão; de Souza, Lauro Mera; Lourenço, Emerson Luiz Botelho; Gasparotto Junior, Arquimedes


    -EG. The 7-day treatment with ES-EG resulted in increased plasma nitrite levels. All other parameters were not affected by treatment with ES-EG. Our results suggest that the mechanisms through which Echinodorus grandiflorus extracts induce prolonged diuresis and reduce blood pressure in normotensive and 2K1C rats are mainly related to activation of muscarinic and bradykinin receptors with direct effects on prostaglandins and nitric oxide pathways. Copyright © 2015. Published by Elsevier GmbH.

  16. 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.

  17. 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.

  18. Amygdala EphB2 Signaling Regulates Glutamatergic Neuron Maturation and Innate Fear. (United States)

    Zhu, Xiao-Na; Liu, Xian-Dong; Zhuang, Hanyi; Henkemeyer, Mark; Yang, Jing-Yu; Xu, Nan-Jie


    The amygdala serves as emotional center to mediate innate fear behaviors that are reflected through neuronal responses to environmental aversive cues. However, the molecular mechanism underlying the initial neuron responses is poorly understood. In this study, we monitored the innate defensive responses to aversive stimuli of either elevated plus maze or predator odor in juvenile mice and found that glutamatergic neurons were activated in amygdala. Loss of EphB2, a receptor tyrosine kinase expressed in amygdala neurons, suppressed the reactions and led to defects in spine morphogenesis and fear behaviors. We further found a coupling of spinogenesis with these threat cues induced neuron activation in developing amygdala that was controlled by EphB2. A constitutively active form of EphB2 was sufficient to rescue the behavioral and morphological defects caused by ablation of ephrin-B3, a brain-enriched ligand to EphB2. These data suggest that kinase-dependent EphB2 intracellular signaling plays a major role for innate fear responses during the critical developing period, in which spinogenesis in amygdala glutamatergic neurons was involved. Generation of innate fear responses to threat as an evolutionally conserved brain feature relies on development of functional neural circuit in amygdala, but the molecular mechanism remains largely unknown. We here identify that EphB2 receptor tyrosine kinase, which is specifically expressed in glutamatergic neurons, is required for the innate fear responses in the neonatal brain. We further reveal that EphB2 mediates coordination of spinogenesis and neuron activation in amygdala during the critical period for the innate fear. EphB2 catalytic activity plays a major role for the behavior upon EphB-ephrin-B3 binding and transnucleus neuronal connections. Our work thus indicates an essential synaptic molecular signaling within amygdala that controls synapse development and helps bring about innate fear emotions in the postnatal

  19. Ablation of kappa-opioid receptors from brain dopamine neurons has anxiolytic-like effects and enhances cocaine-induced plasticity. (United States)

    Van't Veer, Ashlee; Bechtholt, Anita J; Onvani, Sara; Potter, David; Wang, Yujun; Liu-Chen, Lee-Yuan; Schütz, Günther; Chartoff, Elena H; Rudolph, Uwe; Cohen, Bruce M; Carlezon, William A


    Brain kappa-opioid receptors (KORs) are implicated in states of motivation and emotion. Activation of KORs negatively regulates mesolimbic dopamine (DA) neurons, and KOR agonists produce depressive-like behavioral effects. To further evaluate how KOR function affects behavior, we developed mutant mice in which exon 3 of the KOR gene (Oprk1) was flanked with Cre-lox recombination (loxP) sites. By breeding these mice with lines that express Cre-recombinase (Cre) in early embryogenesis (EIIa-Cre) or only in DA neurons (dopamine transporter (DAT)-Cre), we developed constitutive KOR knockouts (KOR(-/-)) and conditional knockouts that lack KORs in DA-containing neurons (DAT-KOR(lox/lox)). Autoradiography demonstrated complete ablation of KOR binding in the KOR(-/-) mutants, and reduced binding in the DAT-KOR(lox/lox) mutants. Quantitative reverse transcription PCR (qPCR) studies confirmed that KOR mRNA is undetectable in the constitutive mutants and reduced in the midbrain DA systems of the conditional mutants. Behavioral characterization demonstrated that these mutant lines do not differ from controls in metrics, including hearing, vision, weight, and locomotor activity. Whereas KOR(-/-) mice appeared normal in the open field and light/dark box tests, DAT-KOR(lox/lox) mice showed reduced anxiety-like behavior, an effect that is broadly consistent with previously reported effects of KOR antagonists. Sensitization to the locomotor-stimulating effects of cocaine appeared normal in KOR(-/-) mutants, but was exaggerated in DAT-KOR(lox/lox) mutants. Increased sensitivity to cocaine in the DAT-KOR(lox/lox) mutants is consistent with a role for KORs in negative regulation of DA function, whereas the lack of differences in the KOR(-/-) mutants suggests compensatory adaptations after constitutive receptor ablation. These mouse lines may be useful in future studies of KOR function.

  20. A novel antihypertension agent, sargachromenol D from marine brown algae, Sargassum siliquastrum, exerts dual action as an L-type Ca(2+) channel blocker and endothelin A/B2 receptor antagonist. (United States)

    Park, Byong-Gon; Shin, Woon-Seob; Oh, Sangtae; Park, Gab-Man; Kim, Nam Ik; Lee, Seokjoon


    We isolated the novel vasoactive marine natural products, (5E,10E)-14-hydroxy-2,6,10-trimethylpentadeca-5,10-dien-4-one (4) and sargachromenol D (5), from Sargassum siliquastrum collected from the coast of the East Sea in South Korea by using activity-guided HPLC purification. The compounds effectively dilated depolarization (50mMK(+))-induced basilar artery contraction with EC50 values of 3.52±0.42 and 1.62±0.63μM, respectively, but only sargachromenol D (5) showed a vasodilatory effect on endothelin-1 (ET-1)-induced basilar artery contraction (EC50=9.8±0.6μM). These results indicated that sargachromenol D (5) could act as a dual antagonist of l-type Ca(2+) channel and endothelin A/B2 receptors. Moreover, sargachromenol D (5) lowered blood pressure in spontaneous hypertensive rats (SHRs) 2h after oral treatment at a dose of 80mg/kg dose and the effect was maintained for 24h. Based on our ex vivo and in vivo experiments, we propose that sargachromenol D (5) is a strong candidate for the treatment of hypertension that is not controlled by conventional drugs, in particular, severe-, type II diabetes-, salt-sensitive, and metabolic disease-induced hypertension. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. 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.

  2. Skeletal Muscle-specific G Protein-coupled Receptor Kinase 2 Ablation Alters Isolated Skeletal Muscle Mechanics and Enhances Clenbuterol-stimulated Hypertrophy. (United States)

    Woodall, Benjamin P; Woodall, Meryl C; Luongo, Timothy S; Grisanti, Laurel A; Tilley, Douglas G; Elrod, John W; Koch, Walter J


    GRK2, a G protein-coupled receptor kinase, plays a critical role in cardiac physiology. Adrenergic receptors are the primary target for GRK2 activity in the heart; phosphorylation by GRK2 leads to desensitization of these receptors. As such, levels of GRK2 activity in the heart directly correlate with cardiac contractile function. Furthermore, increased expression of GRK2 after cardiac insult exacerbates injury and speeds progression to heart failure. Despite the importance of this kinase in both the physiology and pathophysiology of the heart, relatively little is known about the role of GRK2 in skeletal muscle function and disease. In this study we generated a novel skeletal muscle-specific GRK2 knock-out (KO) mouse (MLC-Cre:GRK2(fl/fl)) to gain a better understanding of the role of GRK2 in skeletal muscle physiology. In isolated muscle mechanics testing, GRK2 ablation caused a significant decrease in the specific force of contraction of the fast-twitch extensor digitorum longus muscle yet had no effect on the slow-twitch soleus muscle. Despite these effects in isolated muscle, exercise capacity was not altered in MLC-Cre:GRK2(fl/fl) mice compared with wild-type controls. Skeletal muscle hypertrophy stimulated by clenbuterol, a β2-adrenergic receptor (β2AR) agonist, was significantly enhanced in MLC-Cre:GRK2(fl/fl) mice; mechanistically, this seems to be due to increased clenbuterol-stimulated pro-hypertrophic Akt signaling in the GRK2 KO skeletal muscle. In summary, our study provides the first insights into the role of GRK2 in skeletal muscle physiology and points to a role for GRK2 as a modulator of contractile properties in skeletal muscle as well as β2AR-induced hypertrophy. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. 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



  4. Resolving pathobiological mechanisms relating to Huntington disease: gait, balance, and involuntary movements in mice with targeted ablation of striatal D1 dopamine receptor cells. (United States)

    Kim, Hyun Ah; Jiang, Luning; Madsen, Heather; Parish, Clare L; Massalas, Jim; Smardencas, Arthur; O'Leary, Claire; Gantois, Ilse; O'Tuathaigh, Colm; Waddington, John L; Ehrlich, Michelle E; Lawrence, Andrew J; Drago, John


    Progressive cell loss is observed in the striatum, cerebral cortex, thalamus, hypothalamus, subthalamic nucleus and hippocampus in Huntington disease. In the striatum, dopamine-responsive medium spiny neurons are preferentially lost. Clinical features include involuntary movements, gait and orofacial impairments in addition to cognitive deficits and psychosis, anxiety and mood disorders. We utilized the Cre-LoxP system to generate mutant mice with selective postnatal ablation of D1 dopamine receptor-expressing striatal neurons to determine which elements of the complex Huntington disease phenotype relate to loss of this neuronal subpopulation. Mutant mice had reduced body weight, locomotor slowing, reduced rearing, ataxia, a short stride length wide-based erratic gait, impairment in orofacial movements and displayed haloperidol-suppressible tic-like movements. The mutation was associated with an anxiolytic profile. Mutant mice had significant striatal-specific atrophy and astrogliosis. D1-expressing cell number was reduced throughout the rostrocaudal extent of the dorsal striatum consistent with partial destruction of the striatonigral pathway. Additional striatal changes included up-regulated D2 and enkephalin mRNA, and an increased density of D2 and preproenkephalin-expressing projection neurons, and striatal neuropeptide Y and cholinergic interneurons. These data suggest that striatal D1-cell-ablation alone may account for the involuntary movements and locomotor, balance and orofacial deficits seen not only in HD but also in HD phenocopy syndromes with striatal atrophy. Therapeutic strategies would therefore need to target striatal D1 cells to ameliorate deficits especially when the clinical presentation is dominated by a bradykinetic/ataxic phenotype with involuntary movements. © 2013 Elsevier Inc. All rights reserved.

  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. Conditional ablation of neuroligin-1 in CA1 pyramidal neurons blocks LTP by a cell-autonomous NMDA receptor-independent mechanism (United States)

    Jiang, Man; Polepalli, Jai; Chen, Lulu Y.; Zhang, Bo; Südhof, Thomas C.; Malenka, Robert C.


    Neuroligins are postsynaptic cell-adhesion molecules implicated in autism and other neuropsychiatric disorders. Despite extensive work, the role of neuroligins in synapse function and plasticity, especially NMDA receptor (NMDAR)-dependent LTP, remains unclear. To establish which synaptic functions unequivocally require neuroligins, we analyzed single and triple conditional knockout (cKO) mice for all three major neuroligin isoforms (NL1-NL3). We inactivated neuroligins by stereotactic viral expression of Cre-recombinase in hippocampal CA1 region pyramidal neurons at postnatal day 0 (P0) or day 21 (P21), and measured synaptic function, synaptic plasticity, and spine numbers in acute hippocampal slices 2–3 weeks later. Surprisingly, we find that ablation of neuroligins in newborn or juvenile mice only modestly impaired basal synaptic function in hippocampus, and caused no alteration in postsynaptic spine numbers. However, triple cKO of NL1-NL3 or single cKO of NL1 impaired NMDAR-mediated excitatory postsynaptic currents (NMDAR EPSCs), and abolished NMDAR-dependent LTP. Strikingly, the NL1 cKO also abolished LTP elicited by activation of L-type Ca2+-channels during blockade of NMDARs. These findings demonstrate that neuroligins are generally not essential for synapse formation in CA1 pyramidal neurons but shape synaptic properties and that NL1 specifically is required for LTP induced by postsynaptic Ca2+-elevations, a function which may contribute to the pathophysiological role of neuroligins in brain disorders. PMID:27217145

  7. Colitogenic role of tumour necrosis factor (TNF) receptors in trinitrobenzene sulphonic acid colitis: TNF-R1 ablation does not affect systemic inflammatory response. (United States)

    Yang, Y; Wang, H; Dou, Y; Wang, Y; Han, G; Wang, Renxi; Wang, L; Guo, R; Xiao, H; Li, X; Shen, B; Shi, Y; Chen, G; Li, Y


    Tumour necrosis factor (TNF)-α plays a critical role in the pathogenesis of T helper type 1-mediated colitis such as Crohn's disease. However, the roles of its two receptors in mediating pathology remain largely unknown. In this study, trinitrobenzene sulphonic acid (TNBS) was used to induce colitis in TNF-receptor single or double knock-out (DKO) BALB/c mice and in wild-type counterparts. TNF-R1(-/-) mice had significantly less weight loss, reduced mortality, colon shortening and oedema, colon histological damage and lower levels of colon myeloperoxidase compared with wild-type (WT) BALB/c mice. A similar manifestation was also observed in TNF-R2(-/-) and TNF-R1(-/-) TNF-R2(-/-) (TNF-R DKO) mice. Strikingly, systemic inflammatory response (including splenomegaly and monocyte expansion) was found in WT and TNF-R1(-/-) mice after TNBS, instead of TNF-R2(-/-) and TNF-R DKO mice. Attenuated pathology of colitis in TNF-R1(-/-) or TNF-R2(-/-) mice correlated with lower amounts of interleukin (IL)-6, IL-1β, monocyte chemotactic protein (MCP)-1, IL-12p70 and interferon (IFN)-γ production in the colons. Importantly, ablation of TNF-R1 or TNF-R2 reduced the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelling (TUNEL)-positive apoptotic epithelial cells in the affected colons compared with WT TNBS-instilled controls, which might be due to the heightened ratio of Bcl-2/Bax and reduced activity of nuclear factor (NF)-κB. These findings suggest that either TNF-R1 or TNF-R2 plays a pathogenic role in the pathology of colitis and TNF signalling via TNF-R1 or TNF-R2 alone is not sufficient for inducing mucosal damage.

  8. Genetic ablation of androgen receptor signaling in fetal Leydig cell lineage affects Leydig cell functions in adult testis. (United States)

    Kaftanovskaya, Elena M; Lopez, Carolina; Ferguson, Lydia; Myhr, Courtney; Agoulnik, Alexander I


    It is commonly accepted that androgen-producing fetal Leydig cells (FLC) are substituted by adult Leydig cells (ALC) during perinatal testis development. The mechanisms influencing this process are unclear. We used mice with a retinoid acid receptor 2 promoter-Cre recombinase transgene (Rarb-cre) expressed in embryonic FLC precursors, but not in postnatal testis, and a dual fluorescent Cre recombinase reporter to label FLC and ALC in vivo. All FLC in newborn testis had the recombinant, whereas the majority of LC in adult testis had the nonrecombinant reporter. Primary LC cultures from adult testis had either recombinant (20%) or nonrecombinant (80%) cells, demonstrating that the FLC survive in adult testis and their ontogeny is distinct from ALC. Conditional inactivation of androgen receptor (AR) allele using the Rarb-cre transgene resulted in a 50% increase of AR-negative LC in adult testis. The mutant males became infertile with age, with all LC in older testis showing signs of incomplete differentiation, such as a large number of big lipid droplets, an increase of finger-like protrusions, and a misexpression of steroidogenic or FLC- and ALC-specific genes. We propose that the antiandrogenic exposure during early development may similarly result in an increase of FLC in adult testis, leading to abnormal LC differentiation.

  9. Ablation of sphingosine 1-phosphate receptor subtype 3 impairs hippocampal neuron excitability in vitro and spatial working memory in vivo

    Directory of Open Access Journals (Sweden)

    Daniela Weth-Malsch


    Full Text Available Understanding the role of the bioactive lipid mediator sphingosine 1-phosphate (S1P within the central nervous system has recently gained more and more attention, as it has been connected to major diseases such as multiple sclerosis and Alzheimer's disease. Even though much data about the functions of the five S1P receptors has been collected for other organ systems, we still lack a complete understanding for their specific roles, in particular within the brain. Therefore, it was the aim of this study to further elucidate the role of S1P receptor subtype 3 (S1P3 in vivo and in vitro with a special focus on the hippocampus. Using an S1P3 knock-out mouse model we applied a range of behavioral tests, performed expression studies and whole cell patch clamp recordings in acute hippocampal slices. We were able to show that S1P3 deficient mice display a significant spatial working memory deficit within the T-maze test, but not in anxiety related tests. Furthermore, S1p3 mRNA was expressed throughout the hippocampal formation. Principal neurons in area CA3 lacking S1P3 showed significantly increased interspike intervals and a significantly decreased input resistance. Upon stimulation with S1P CA3 principal neurons from both wildtype and S1P3-/- mice displayed significantly increased evoked EPSC amplitudes and decay times, whereas rise times remained unchanged. These results suggest a specific involvement of S1P3 for the establishment of spatial working memory and neuronal excitability within the hippocampus.

  10. Chicken Ig-like receptor B2, a member of a multigene family, is mainly expressed on B lymphocytes, recruits both Src homology 2 domain containing protein tyrosine phosphatase (SHP)-1 and SHP-2, and inhibits proliferation

    NARCIS (Netherlands)

    Viertlboeck, B.C.; Crooijmans, R.P.M.A.; Groenen, M.A.M.; Gobel, T.W.


    Ig-like inhibitory receptors have been the focus of intensive research particularly in mouse and human. We report the cloning and characterization of three novel inhibitory chicken Ig-like receptors (CHIR) that display a two Ig-domain extracellular structure, a transmembrane region lacking charged

  11. In vitro gamma oscillations following partial and complete ablation of δ subunit-containing GABAA receptors from parvalbumin interneurons. (United States)

    Ferando, Isabella; Mody, Istvan


    Perisynaptic and extrasynaptic δ subunit-containing GABAA receptors (δ-GABAARs) mediate tonic conductances in many neurons. On principal cells of the neocortex and hippocampus they comprise α4 subunits, whereas they usually contain α1 on various interneurons. Specific characteristics of δ-GABAARs are their pharmacology and high plasticity. In particular δ-GABAARs are sensitive to low concentrations of neurosteroids (NS) and during times of altered NS production (stress, puberty, ovarian cycle and pregnancy) δ-GABAARs expression varies in many neurons regardless of the α subunits they contain, with direct consequences for neuronal excitability and network synchrony. For example δ-GABAARs plasticity on INs underlies modifications in hippocampal γ oscillations during pregnancy or over the ovarian cycle. Most δ-GABAAR-expressing INs in CA3 stratum pyramidale (SP) are parvalbumin (PV) + INs, whose fundamental role in γ oscillations generation and control has been extensively investigated. In this study we reduced or deleted δ-subunits in PV + INs, with the use of a PV/Cre-Gabrd/floxed genetic system. We find that in vitro CA3 γ oscillations of both PV-Gabrd(+/-)and PV-Gabrd(-/-) mice are characterized by higher frequencies than WT controls. The increased frequencies could be lowered to control levels in PV-Gabrd(+/-) by the NS allopregnanolone (3α,5α-tetrahydroprogesterone, 100 nM) but not the synthetic δ-GABAAR positive allosteric modulator 4-Chloro-N-[2-(2-thienyl)imidazo[1,2-a]pyridin-3-yl] benzamide (DS-2, 10 μM). This is consistent with the idea that DS-2, in contrast to ALLO, selectively targets α4/δ-GABAARs but not the α1/δ-GABAARs found on INs. Therefore, development of drugs selective for IN-specific α1/δ-GABAARs may be useful in neurological and psychiatric conditions correlated with altered PV + IN function and aberrant γ oscillations.

  12. Diagnostics of laser ablated plasma plumes

    DEFF Research Database (Denmark)

    Amoruso, S.; Toftmann, B.; Schou, Jørgen;


    The effect of an ambient gas on the expansion dynamics of laser ablated plasmas has been studied for two systems by exploiting different diagnostic techniques. First, the dynamics of a MgB2 laser produced plasma plume in an Ar atmosphere has been investigated by space-and time-resolved optical...

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. Myocardial Ablation of G Protein-Coupled Receptor Kinase 2 (GRK2 Decreases Ischemia/Reperfusion Injury through an Anti-Intrinsic Apoptotic Pathway.

    Directory of Open Access Journals (Sweden)

    Qian Fan

    Full Text Available Studies from our lab have shown that decreasing myocardial G protein-coupled receptor kinase 2 (GRK2 activity and expression can prevent heart failure progression after myocardial infarction. Since GRK2 appears to also act as a pro-death kinase in myocytes, we investigated the effect of cardiomyocyte-specific GRK2 ablation on the acute response to cardiac ischemia/reperfusion (I/R injury. To do this we utilized two independent lines of GRK2 knockout (KO mice where the GRK2 gene was deleted in only cardiomyocytes either constitutively at birth or in an inducible manner that occurred in adult mice prior to I/R. These GRK2 KO mice and appropriate control mice were subjected to a sham procedure or 30 min of myocardial ischemia via coronary artery ligation followed by 24 hrs reperfusion. Echocardiography and hemodynamic measurements showed significantly improved post-I/R cardiac function in both GRK2 KO lines, which correlated with smaller infarct sizes in GRK2 KO mice compared to controls. Moreover, there was significantly less TUNEL positive myocytes, less caspase-3, and -9 but not caspase-8 activities in GRK2 KO mice compared to control mice after I/R injury. Of note, we found that lowering cardiac GRK2 expression was associated with significantly lower cytosolic cytochrome C levels in both lines of GRK2 KO mice after I/R compared to corresponding control animals. Mechanistically, the anti-apoptotic effects of lowering GRK2 expression were accompanied by increased levels of Bcl-2, Bcl-xl, and increased activation of Akt after I/R injury. These findings were reproduced in vitro in cultured cardiomyocytes and GRK2 mRNA silencing. Therefore, lowering GRK2 expression in cardiomyocytes limits I/R-induced injury and improves post-ischemia recovery by decreasing myocyte apoptosis at least partially via Akt/Bcl-2 mediated mitochondrial protection and implicates mitochondrial-dependent actions, solidifying GRK2 as a pro-death kinase in the heart.

  18. 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

  19. 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.

  20. 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...

  1. 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...

  2. The Mysterious Ways of ErbB2/HER2 Trafficking

    Directory of Open Access Journals (Sweden)

    Vibeke Bertelsen


    Full Text Available The EGFR- or ErbB-family of receptor tyrosine kinases consists of EGFR/ErbB1, ErbB2/HER2, ErbB3/HER3 and ErbB4/HER4. Receptor activation and downstream signaling are generally initiated upon ligand-induced receptor homo- or heterodimerization at the plasma membrane, and endocytosis and intracellular membrane transport are crucial for regulation of the signaling outcome. Among the receptors, ErbB2 is special in several ways. Unlike the others, ErbB2 has no known ligand, but is still the favored dimerization partner. Furthermore, while the other receptors are down-regulated either constitutively or upon ligand-binding, ErbB2 is resistant to down-regulation, and also inhibits down-regulation of its partner upon heterodimerization. The reason(s why ErbB2 is resistant to down-regulation are the subject of debate. Contrary to other ErbB-proteins, mature ErbB2 needs Hsp90 as chaperone. Several data suggest that Hsp90 is an important regulator of factors like ErbB2 stability, dimerization and/or signaling. Hsp90 inhibitors induce degradation of ErbB2, but whether Hsp90 directly makes ErbB2 endocytosis resistant is unclear. Exposure to anti-ErbB2 antibodies can also induce down-regulation of ErbB2. Down-regulation induced by Hsp90 inhibitors or antibodies does at least partly involve internalization and endosomal sorting to lysosomes for degradation, but also retrograde trafficking to the nucleus has been reported. In this review, we will discuss different molecular mechanisms suggested to be important for making ErbB2 resistant to down-regulation, and review how membrane trafficking is involved when down-regulation and/or relocalization of ErbB2 is induced.

  3. 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.

  4. 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

  5. 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.

  6. A Phase I-II Study of Combined Blockade of the ErbB Receptor Network with Trastuzumab and Gefitinib in Patients with HER2 (ErbB2)-Overexpressing Metastatic Breast Cancer (United States)

    Arteaga, Carlos L.; O’Neill, Anne; Moulder, Stacy L.; Pins, Michael; Sparano, Joseph A.; Sledge, George W.; Davidson, Nancy E.


    Purpose To determine the safety, and efficacy of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib in combination with trastuzumab in patients with metastatic HER2-positive metastatic breast cancer. Experimental Design Patients with HER2-overexpressing breast cancer were treated with trastuzumab 2 mg/kg/week and gefitinib 250 to 500 mg/day. The primary end point of the study was to increase the proportion progression-free from 50% to 65% at 6 months in chemotherapy-naive patients and from 50% to 70% at 3 months in patients previously treated with chemotherapy in the metastatic setting. Results In the phase I study, all patients treated with gefitinib 500 mg/day developed grade 3 diarrhea. The phase II study was conducted using trastuzumab and gefitinib 250 mg/day. One patient achieved a complete response, 2 had a partial response, and 6 had stable disease for an overall response rate of 9% and a clinical benefit rate of 28% (9 of 32). Median time to progression (TTP) was 3 months (95% confidence interval, 2.3-4.1) in patients with no prior systemic therapy in the metastatic setting (n = 23). In patients treated with prior systemic therapy (n = 9), the median TTP of 5.3 months (95% confidence interval, 2.8-8.1). Overall median survival was 27 months. TTP was similar in EGFR-positive compared with EGFR-negative patients. Conclusions Gefitinib 250 mg/day was the maximal dose that can be safely administered with weekly trastuzumab. Interim analysis of the efficacy suggested that the combination was unlikely to result in clinical benefit compared with trastuzumab alone. These results do not support the use of this combination in patients with HER2-positive breast cancer. PMID:18829509

  7. 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.

  8. 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...

  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. 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

  11. 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).

  12. 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.

  13. 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 ...

  14. Ablation of the PTHrP gene or the PTH/PTHrP receptor gene leads to distinct abnormalities in bone development


    Lanske, Beate; Amling, Michael; Neff, Lynn; Guiducci, Jennifer; Baron, Roland; Kronenberg, Henry M.


    Parathyroid hormone (PTH) and parathyroid hormone–related peptide (PTHrP) bind to and activate the same PTH/PTHrP receptor. Deletion of either the PTHrP gene or the PTH/PTHrP receptor gene leads to acceleration of differentiation of growth plate chondrocytes. To explore further the functional relationships of PTHrP and the PTH/PTHrP receptor, bones of knockout mice were analyzed early in development, and the phenotypes of double-knockout mice were characterized.

  15. 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.

  16. Anticonvulsant activity of B2, an adenosine analog, on chemical convulsant-induced seizures.

    Directory of Open Access Journals (Sweden)

    Min Li

    Full Text Available Epilepsy is a chronic neurological disorder characterized by recurrent seizures. However, approximately one-third of epilepsy patients still suffer from uncontrolled seizures. Effective treatments for epilepsy are yet to be developed. N (6-(3-methoxyl-4-hydroxybenzyl adenine riboside (B2 is a N(6-substitued adenosine analog. Here we describe an investigation of the effects and mechanisms of B2 on chemical convulsant-induced seizures. Seizures were induced in mice by administration of 4-aminopyridine (4-AP, pentylenetetrazol (PTZ, picrotoxin, kainite acid (KA, or strychnine. B2 has a dose-related anticonvulsant effect in these chemical-induced seizure models. The protective effects of B2 include increased latency of seizure onset, decreased seizure occurrence, shorter seizure duration and reduced mortality rate. Radioligand binding and cAMP accumulation assays indicated that B2 might be a functional ligand for both adenosine A1 and A2A receptors. Furthermore, DPCPX, a selective A1 receptor antagonist, but not SCH58261, a selective A2A receptor antagonist, blocked the anticonvulsant effect of B2 on PTZ-induced seizure. c-Fos is a cellular marker for neuronal activity. Immunohistochemical and western blot analyses indicated that B2 significantly reversed PTZ-induced c-Fos expression in the hippocampus. Together, these results indicate that B2 has significant anticonvulsant effects. The anticonvulsant effects of B2 may be attributed to adenosine A1 receptor activation and reduced neuronal excitability in the hippocampus. These observations also support that the use of adenosine receptor agonist may be a promising approach for the treatment of epilepsy.

  17. 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.

  18. 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.

  19. The correlation between power Doppler imaging and the expressions of estrogen receptor, progesteron receptor and CerbB-2 in primary breast cancer%乳腺癌能量多普勒超声与乳腺癌雌激素受体、孕激素受体及人类癌基因的相关性研究

    Institute of Scientific and Technical Information of China (English)

    刘洋; 林奇; 张天艳


    目的 探讨乳腺癌能量多普勒超声(PDI)与乳腺癌雌激素受体(ER)、孕激素受体(PR)以及人类癌基因(CerbB-2)表达的相关性.方法 选择30例乳腺癌患者术前用PDI检查,术后用免疫组化法检测肿瘤组织ER、PR及CerbB-2蛋白的表达.结果 乳腺癌PDI显示分级为Ⅱ~Ⅲ级,其ER 、PR 阳性率明显低于分级为0~Ⅰ级的病例(P<0.01);而CerbB-2阳性率则高于对应病例(P<0.05).结论乳腺癌PDI与CerbB-2、ER、PR 的表达具有相关性,可以通过PDI和免疫组化的结合去判断乳腺癌的恶性程度和预后.

  20. Laser ablation principles and applications

    CERN Document Server


    Laser Ablation provides a broad picture of the current understanding of laser ablation and its many applications, from the views of key contributors to the field. Discussed are in detail the electronic processes in laser ablation of semiconductors and insulators, the post-ionization of laser-desorbed biomolecules, Fourier-transform mass spectroscopy, the interaction of laser radiation with organic polymers, laser ablation and optical surface damage, laser desorption/ablation with laser detection, and laser ablation of superconducting thin films.

  1. Pharmacological therapy following catheter ablation of atrial fibrillation. (United States)

    Rordorf, Roberto; Savastano, Simone; Gandolfi, Edoardo; Vicentini, Alessandro; Petracci, Barbara; Landolina, Maurizio


    Catheter ablation has been proven to be an effective treatment for patients with drug-resistant atrial fibrillation. Nevertheless its efficacy is limited to 60-80% of patients in different studies. Whether the use of pharmacological therapy after catheter ablation of atrial fibrillation might increase the procedural success rate is still a matter of debate. There is general agreement that antiarrhythmic drugs (AADs) are useful in the management of arrhythmias occurring in the very early period after catheter ablation (blanking period). On the contrary, limited data are available on the efficacy of AADs over a longer period. Some patients remain free of arrhythmia recurrences by the use of AADs that were ineffective before catheter ablation: whether this latter situation is to be considered a partial success of catheter ablation or a treatment failure, thus demanding a redo procedure, is still an open question. Some studies have also investigated the role of non-AADs [angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, statins and corticosteroids] in preventing atrial fibrillation recurrences after catheter ablation, reporting conflicting results. Whereas there is a general consensus on the use of anticoagulation therapy in the first phase after catheter ablation, no definite data are available on the proper long-term management of anticoagulation therapy after catheter ablation. This review focuses on the still open issue of what is the optimal pharmacological treatment of patients after catheter ablation of atrial fibrillation.

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

    DEFF Research Database (Denmark)

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


    It has been suggested previously ( AbdAlla, S., Lother, H., and Quitterer, U. (2000) Nature 407, 94-98 ) that the angiotensin II type 1 receptor (AT1R) and the bradykinin B2 receptor (B2R) form constitutive heterodimers. Furthermore they demonstrate that AT1R signaling significantly increases...... in the presence of the B2R. These findings suggest that heterodimerization and potentiation of AT1R signaling is a universal phenomenon that occurs as a natural consequence of simultaneous expression of the two receptors. Hence this potential interaction is of great pharmacological and biological interest...... by or physical interaction between the two receptor proteins. In contrast to the previous observations, our data collectively suggest that AT1R/B2R heterodimerization does not occur as a natural consequence of their simultaneous expression in the same cell nor does the B2R influence the AT1R signaling....

  3. 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.

  4. Interstellar hydroxyl near Sagittarius B2

    Energy Technology Data Exchange (ETDEWEB)

    Venger, A.; Gosachinskii, I.; Grachev, V.; Egorova, T.; Prozorov, V.; Ryzhkov, N.; Khersonskii, V.; Yudaeva, N.


    The 1665-, 1667-MHz OH absorption lines near the radio source Sgr B2 have been observed with the RATAN-600 radio telescope at 2'.2 x 47' x 5.4 km/sec resolution. Physical parameters are determined for the five OH clouds observed in this direction at positive radial velocities. Evidently only one of these clouds can have any connection with the Sgr B2 source; it is located at the edge of the gas envelope surrounding that source.

  5. 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

  6. 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

  7. Antenatal management of recurrent fetal goitrous hyperthyroidism associated with fetal cardiac failure in a pregnant woman with persistent high levels of thyroid-stimulating hormone receptor antibody after ablative therapy. (United States)

    Matsumoto, Tadashi; Miyakoshi, Kei; Saisho, Yoshifumi; Ishii, Tomohiro; Ikenoue, Satoru; Kasuga, Yoshifumi; Kadohira, Ikuko; Sato, Seiji; Momotani, Naoko; Minegishi, Kazuhiro; Yoshimura, Yasunori


    High titer of maternal thyroid-stimulating hormone receptor antibody (TRAb) in patients with Graves' disease could cause fetal hyperthyroidism during pregnancy. Clinical features of fetal hyperthyroidism include tachycardia, goiter, growth restriction, advanced bone maturation, cardiomegaly, and fetal death. The recognition and treatment of fetal hyperthyroidism are believed to be important to optimize growth and intellectual development in affected fetuses. We herein report a case of fetal treatment in two successive siblings showing in utero hyperthyroid status in a woman with a history of ablative treatment for Graves' disease. The fetuses were considered in hyperthyroid status based on high levels of maternal TRAb, a goiter, and persistent tachycardia. In particular, cardiac failure was observed in the second fetus. With intrauterine treatment using potassium iodine and propylthiouracil, fetal cardiac function improved. A high level of TRAb was detected in the both neonates. To the best of our knowledge, this is the first report on the changes of fetal cardiac function in response to fetal treatment in two siblings showing in utero hyperthyroid status. This case report illustrates the impact of prenatal medication via the maternal circulation for fetal hyperthyroidism and cardiac failure.

  8. Mammary-Specific Ablation of the Calcium-Sensing Receptor During Lactation Alters Maternal Calcium Metabolism, Milk Calcium Transport, and Neonatal Calcium Accrual


    Mamillapalli, Ramanaiah; VanHouten, Joshua; Dann, Pamela; Bikle, Daniel; Chang, Wenhan; Brown, Edward; Wysolmerski, John


    To meet the demands for milk calcium, the lactating mother adjusts systemic calcium and bone metabolism by increasing dietary calcium intake, increasing bone resorption, and reducing renal calcium excretion. As part of this adaptation, the lactating mammary gland secretes PTHrP into the maternal circulation to increase bone turnover and mobilize skeletal calcium stores. Previous data have suggested that, during lactation, the breast relies on the calcium-sensing receptor (CaSR) to coordinate ...

  9. Radiofrequency ablation in dermatology

    Directory of Open Access Journals (Sweden)

    Sachdeva Silonie


    Full Text Available Radiofreqeuency ablation is a versatile dermatosurgical procedure used for surgical management of skin lesions by using various forms of alternating current at an ultra high frequency. The major modalities in radiofrequency are electrosection, electrocoagulation, electrodessication and fulguration. The use of radiofrequency ablation in dermatosurgical practice has gained importance in recent years as it can be used to treat most of the skin lesions with ease in less time with clean surgical field due to adequate hemostasis and with minimal side effects and complications. This article focuses on the major tissue effects and factors influencing radiofrequency ablation and its application for various dermatological conditions.

  10. HCl absorption toward Sagittarius B2 (United States)

    Zmuidzinas, J.; Blake, G. A.; Carlstrom, J.; Keene, J.; Miller, D.


    We have detected the 626 GHz J = 1 approaches 0 transition of hydrogen chloride (H(sup 35)Cl) in absorption against the blending of the three hyperfine components of this transition by the velocity profile of Sgr B2 observed in other species. The apparent optical depth of the line is tau approximately equal to 1, and the minimum HCl column density is 1.6 x 10(exp 14)/sq cm. A detailed radiative transfer model was constructed which includes collisional and radiative excitation, absorption and emission by dust, and the radial variation of temperature and density. Good agreement between the model and the data is obtained for HCl/H2 approximately 1.1 x 10(exp -9). Comparison of this result to chemical models indicates that the depletion factor of gas-phase chlorine is between 50-180 in the molecular envelope surrounding the SgrB2(N) and (M) dust cores.

  11. 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.

  12. 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.

  13. Moldable cork ablation material (United States)


    A successful thermal ablative material was manufactured. Moldable cork sheets were tested for density, tensile strength, tensile elongation, thermal conductivity, compression set, and specific heat. A moldable cork sheet, therefore, was established as a realistic product.

  14. femtosecond laser ablation


    Margetic, Vanja


    Femtosecond laser ablation was investigated as a solid sampling method for elemental chemical analysis. In comparison to the sampling with longer laser pulses, two aspects could be improved by using ultrashort pulses: elimination of the elemental fractionation from the ablation crater, which is necessary for an accurate quantitative analysis, and better control of the material removal (especially for metals), which increases the spatial resolution of microanalysis. Basic aspects of ultrashort...

  15. 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

  16. 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.

  17. Interstellar formaldehyde in Sagittarius B2

    Energy Technology Data Exchange (ETDEWEB)

    Gosachinskii, I.V.; Grachev, V.G.; Egorova, T.M.; Zhelenkov, S.R.; Il' in, G.N.; Komar, N.P.; Kurochkina, E.N.; Prozorov, V.A.; Ryzhkov, N.F.


    The 6.2-cm absorption line of the H/sub 2/CO molecule has been observed with the RATAN-600 radio telescope at 0'.8 x 12' resolution. The distribution of H/sub 2/CO optical depth over the radio source Sgr B2 indicates that a gas envelope 11 pc in diameter may be present with a mean radial velocity nearly the same as the recombination-line velocities. The envelope is contracting, at a rate of 20--25 km/sec; it is also rotating at a peripheral velocity of roughly-equal15 km/sec.

  18. UV-laser ablation of sensory cells in living insects (United States)

    Fuhr, G.; Ronacher, B.; Krahe, R.; Fest, S.; Shirley, S. G.; Rogaschewski, S.

    An experimental set-up for applying pulsed UV-laser ablation to the integument of insects and the high precision of ablation is demonstrated. In order to test for possible detrimental effects on physiological responses, this technique was applied to the ears of migratory locust (Locusta migratoria L.). The handling of living insects, the survival, and physiological response after treatment are described. We selectively interrupted the d-receptor of the tympanal organ, which is the receptor system responsible for the locust's sensitivity in the high-frequency range (>10 kHz). The effects of the laser treatment were tested by determining hearing thresholds in electrophysiological recordings from the tympanal nerves. In agreement with the literature, the interruption of the d-receptors led to a significant shift towards higher values of the thresholds in the high-frequency range. Future perspectives and biological applications of UV-laser ablation are discussed.

  19. 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...

  20. Proto-oncogene c-erbB2 initiates rat primordial follicle growth via PKC and MAPK pathways (United States)


    Background c-erbB2, a proto-oncogene coding epidermal growth factor receptor-like receptor, also as a chemosensitivity/prognosis marker for gynecologic cancer, may be involved in initiation of growth of rat primordial follicles. The aim of the present study is to investigate the role and signal pathway of c-erbB2 in onset of rat primordial follicle development. Methods The expression of c-erbB2 mRNA and protein in neonatal ovaries cultured 4 and 8 days with/without epidermal growth factor (EGF) were examined by in situ hybridization, RT-PCR and western blot. The function of c-erbB2 in the primordial folliculogenesis was abolished by small interfering RNA transfection. Furthermore, MAPK inhibitor PD98059 and PKC inhibitor calphostin were used to explore the possible signaling pathway of c-erbB2 in primordial folliculogenesis. Results The results showed that c-erbB2 mRNA was expressed in ooplasm and the expression of c-erbB2 decreased after transfection with c-erbB2 siRNA. Treatment with EGF at 50 ng/ml significantly increased c-erbB2 expression and primary and secondary follicle formation in ovaries. However, this augmenting effect was remarkably inhibited by c-erbB2 siRNA transfection. Furthermore, folliculogenesis offset was blocked by calphostin (5 × 10(-4) mmol/L) and PD98059 (5 × 10(-2) mmol/L), but both did not down-regulate c-erbB2 expression. In contrast, the expressions of p-ERK and p-PKC were decreased obviously by c-erbB2 siRNA transfection. Conclusions c-erbB2 initiates rat primordial follicle growth via PKC and MAPK pathways, suggesting an important role of c-erbB2 in rat primordial follicle initiation and development. PMID:20565902

  1. 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...

  2. Vitamin D Receptor Ablation and Vitamin D Deficiency Result in Reduced Grip Strength, Altered Muscle Fibers, and Increased Myostatin in Mice. (United States)

    Girgis, Christian M; Cha, Kuan Minn; Houweling, Peter J; Rao, Renuka; Mokbel, Nancy; Lin, Mike; Clifton-Bligh, Roderick J; Gunton, Jenny E


    Vitamin D deficiency is associated with muscle weakness, pain, and atrophy. Serum vitamin D predicts muscle strength and age-related muscle changes. However, precise mechanisms by which vitamin D affects skeletal muscle are unclear. To address this question, this study characterizes the muscle phenotype and gene expression of mice with deletion of vitamin D receptor (VDRKO) or diet-induced vitamin D deficiency. VDRKO and vitamin D-deficient mice had significantly weaker grip strength than their controls. Weakness progressed with age and duration of vitamin D deficiency, respectively. Histological assessment showed that VDRKO mice had muscle fibers that were significantly smaller in size and displayed hyper-nuclearity. Real-time PCR also indicated muscle developmental changes in VDRKO mice with dysregulation of myogenic regulatory factors (MRFs) and increased myostatin in quadriceps muscle (>2-fold). Vitamin D-deficient mice also showed increases in myostatin and the atrophy marker E3-ubiqutin ligase MuRF1. As a potential explanation for grip strength weakness, both groups of mice had down-regulation of genes encoding calcium-handling and sarco-endoplasmic reticulum calcium transport ATPase (Serca) channels. This is the first report of reduced strength, morphological, and gene expression changes in VDRKO and vitamin D-deficient mice where confounding by calcium, magnesium, and phosphate have been excluded by direct testing. Although suggested in earlier in vitro work, this study is the first to report an in vivo association between vitamin D, myostatin, and the regulation of muscle mass. These findings support a direct role for vitamin D in muscle function and corroborate earlier work on the presence of VDR in this tissue.


    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.

  4. Transient Ablation of Teflon Hemispheres (United States)

    Arai, Norio; Karashima, Kei-ichi; Sato, Kiyoshi


    For high-speed entry of space vehicles into atmospheric environments, ablation is a practical method for alleviating severe aerodynamic heating. Several studies have been undertaken on steady or quasi-steady ablation. However, ablation is a very complicated phenomenon in which a nonequilibrium chemical process is associated with an aerodynamic process that involves changes in body shape with time. Therefore, it seems realistic to consider that ablation is an unsteady phenomenon. In the design of an ablative heat-shield system, since the ultimate purpose of the heat shield is to keep the internal temperature of the space vehicle at a safe level during entry, the transient heat conduction characteristics of the ablator may be critical in the selection of the material and its thickness. This note presents an experimental study of transient ablation of Teflon, with particular emphasis on the change in body shape, the instantaneous internal temperature distribution, and the effect of thermal expansion on ablation rate.

  5. Power Laser Ablation Symposia

    CERN Document Server

    Phipps, Claude


    Laser ablation describes the interaction of intense optical fields with matter, in which atoms are selectively driven off by thermal or nonthermal mechanisms. The field of laser ablation physics is advancing so rapidly that its principal results are seen only in specialized journals and conferences. This is the first book that combines the most recent results in this rapidly advancing field with authoritative treatment of laser ablation and its applications, including the physics of high-power laser-matter interaction. Many practical applications exist, ranging from inertial confinement fusion to propulsion of aerostats for pollution monitoring to laser ignition of hypersonic engines to laser cleaning nanoscale contaminants in high-volume computer hard drive manufacture to direct observation of the electronic or dissociative states in atoms and molecules, to studying the properties of materials during 200kbar shocks developed in 200fs. Selecting topics which are representative of such a broad field is difficu...

  6. 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.

  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. Sema4C-Plexin B2 signalling modulates ureteric branching in developing kidney. (United States)

    Perälä, Nina; Jakobson, Madis; Ola, Roxana; Fazzari, Pietro; Penachioni, Junia Y; Nymark, Mariann; Tanninen, Tiina; Immonen, Tiina; Tamagnone, Luca; Sariola, Hannu


    Semaphorins, originally identified as axon guidance molecules, have also been implicated in angiogenesis, function of the immune system and cancerous growth. Here we show that deletion of Plexin B2 (Plxnb2), a semaphorin receptor that is expressed both in the pretubular aggregates and the ureteric epithelium in the developing kidney, results in renal hypoplasia and occasional double ureters. The rate of cell proliferation in the ureteric epithelium and consequently the number of ureteric tips are reduced in the kidneys lacking Plexin B2 (Plxnb2-/-). Semaphorin 4C, a ligand for Plexin B2, stimulates branching of the ureteric epithelium in wild type and Plxnb2+/- kidney explants, but not in Plxnb2-/- explants. As shown by co-immunoprecipitation Plexin B2 interacts with the Ret receptor tyrosine kinase, the receptor of Glial-cell-line-derived neurotrophic factor (Gdnf), in embryonic kidneys. Isolated Plxnb2-/- ureteric buds fail to respond to Gdnf by branching, but this response is rescued by Fibroblast growth factor 7 and Follistatin as well as by the metanephric mesenchyme. The differentiation of the nephrogenic mesenchyme, its morphology and the rate of apoptosis in the Plxnb2-/- kidneys are normal. Plexin B2 is co-expressed with Plexin B1 (Plxnb1) in the kidney. The double homozygous Plxnb1-Plxnb2-deficient mice show high embryonic lethality prior to onset of nephrogenesis. The only double homozygous embryo surviving to E12 showed hypoplastic kidneys with ureteric branches and differentiating mesenchyme. Taken together, our results show that Sema4C-Plexin B2 signalling regulates ureteric branching, possibly through modulation of Gdnf signalling by interaction with Ret, and suggest non-redundant roles for Plexin B1 and Plexin B2 in kidney development. Copyright © 2010 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

  9. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

  11. 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.

  12. Tumor ablations in IMRI

    Institute of Scientific and Technical Information of China (English)

    Roberto Blanco Sequeiros


    @@ IntroductionMagnetic resonance imaging based guidance control and monitoring of minimally invasive intervention has developed from a hypothetical concept to a practical possibility. Magnetic-resonance-guided interstitial therapy in principle is defined as a treatment technique for ablating deepseated tumors in the human body.

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 49 CFR 178.33b-2 - Type and size. (United States)


    ... 49 Transportation 2 2010-10-01 2010-10-01 false Type and size. 178.33b-2 Section 178.33b-2 Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS MATERIALS SAFETY... Specifications for Inside Containers, and Linings § 178.33b-2 Type and size. (a) Single-trip inside containers...


    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.

  1. 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...

  2. Role of the monocyte chemoattractant protein-1/C-C chemokine receptor 2 signaling pathway in transient receptor potential vanilloid type 1 ablation-induced renal injury in salt-sensitive hypertension. (United States)

    Wang, Youping; Zhu, Mingjun; Xu, Hui; Cui, Lin; Liu, Weihong; Wang, Xiaoxiao; Shen, Si; Wang, Donna H


    Our recent studies indicate that the transient receptor potential vanilloid type 1 (TRPV1) channel may act as a potential regulator of monocyte/macrophage recruitment to reduce renal injury in salt-sensitive hypertension. This study tests the hypothesis that deletion of TRPV1 exaggerates salt-sensitive hypertension-induced renal injury due to enhanced inflammatory responses via monocyte chemoattractant protein-1 (MCP-1)/C-C chemokine receptor 2 (CCR2)-dependent pathways. Wild type (WT) and TRPV1-null mutant (TRPV1(-/-)) mice were subjected to uninephrectomy and deoxycorticosterone acetate (DOCA)-salt treatment for four weeks with or without the selective CCR2 antagonist, RS504393. DOCA-salt treatment increased systolic blood pressure (SBP) to the same degree in both strains, but increased urinary excretion of albumin and 8-isoprostane and decreased creatinine clearance with greater magnitude in TRPV1(-/-) mice compared to WT mice. DOCA-salt treatment also caused renal glomerulosclerosis, tubulointerstitial injury, collagen deposition, monocyte/macrophage infiltration, proinflammatory cytokine and chemokine production, and NF-κB activation in greater degree in TRPV1(-/-) mice compared to WT mice. Blockade of the CCR2 with RS504393 (4 mg/kg/day) had no effect on SBP in DOCA-salt-treated WT or TRPV1(-/-) mice compared to their respective controls. However, treatment with RS504393 ameliorated renal dysfunction and morphological damage, and prevented the increase in monocyte/macrophage infiltration, cytokine/chemokine production, and NF-κB activity in both DOCA-salt hypertensive strains with a greater effect in DOCA-salt-treated TRPV1(-/-) mice compared to DOCA-salt-treated WT mice. No differences in CCR2 protein expression in kidney were found between DOCA-salt-treated WT and TRPV1(-/-) mice with or without RS504393 treatment. Our studies for the first time indicate that deletion of TRPV1 aggravated renal injury in salt-sensitive hypertension via enhancing MCP-1

  3. Lesion size in relation to ablation site during radiofrequency ablation

    DEFF Research Database (Denmark)

    Petersen, H H; Chen, X; Pietersen, A;


    convective cooling by induction of a flow around the electrode tip increases lesion dimensions and power consumptions. Furthermore we conclude that for the given target temperature the power consumption is positively correlated with lesion volume (p ...This study was designed to investigate the effect of the convective cooling of the tip of the ablation electrode during temperature controlled radiofrequency ablation. In vivo two different application sites in the left ventricle of anaesthetised pigs were ablated and in vitro ablation...... larger for septal applications than apical applications (p convective cooling by induction of flow yielded larger lesion volume, depth and width (p

  4. 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.

  5. 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

  6. Radiofrequency ablation of pulmonary tumors

    Energy Technology Data Exchange (ETDEWEB)

    Crocetti, Laura, E-mail: l.crocetti@med.unipi.i [Division of Diagnostic Imaging and Intervention, Department of Liver Transplants, Hepatology and Infectious Diseases, Pisa University School of Medicine (Italy); Lencioni, Riccardo [Division of Diagnostic Imaging and Intervention, Department of Liver Transplants, Hepatology and Infectious Diseases, Pisa University School of Medicine (Italy)


    The development of image-guided percutaneous techniques for local tumor ablation has been one of the major advances in the treatment of solid tumors. Among these methods, radiofrequency (RF) ablation is currently established as the primary ablative modality at most institutions. RF ablation is accepted as the best therapeutic choice for patients with early-stage hepatocellular carcinoma when liver transplantation or surgical resection are not suitable options and is considered as a viable alternate to surgery for inoperable patients with limited hepatic metastatic disease, especially from colorectal cancer. Recently, RF ablation has been demonstrated to be a safe and valuable treatment option for patients with unresectable or medically inoperable lung malignancies. Resection should remain the standard therapy for non-small cell lung cancer (NSCLC) but RF ablation may be better than conventional external-beam radiation for the treatment of the high-risk individual with NSCLC. Initial favourable outcomes encourage combining radiotherapy and RF ablation, especially for treating larger tumors. In the setting of colorectal cancer lung metastases, survival rates provided by RF ablation in selected patients, are substantially higher than those obtained with any chemotherapy regimens and provide indirect evidence that RF ablation therapy improves survival in patients with limited lung metastatic disease.

  7. 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.

  8. 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”.

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    Flores Juana M


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

  11. Ablation of solids by femtosecond lasers ablation mechanism and ablation thresholds for metals and dielectrics

    CERN Document Server

    Gamaly, E G; Tikhonchuk, V T; Luther-Davies, B


    The mechanism of ablation of solids by intense femtosecond laser pulses is described in an explicit analytical form. It is shown that at high intensities when the ionization of the target material is complete before the end of the pulse, the ablation mechanism is the same for both metals and dielectrics. The physics of this new ablation regime involves ion acceleration in the electrostatic field caused by charge separation created by energetic electrons escaping from the target. The formulae for ablation thresholds and ablation rates for metals and dielectrics, combining the laser and target parameters, are derived and compared to experimental data. The calculated dependence of the ablation thresholds on the pulse duration is in agreement with the experimental data in a femtosecond range, and it is linked to the dependence for nanosecond pulses.

  12. Ablation of solids by femtosecond lasers: ablation mechanism and ablation thresholds for metals and dielectrics


    Gamaly, E. G.; Rode, A. V.; Tikhonchuk, V. T.; Luther-Davies, B.


    The mechanism of ablation of solids by intense femtosecond laser pulses is described in an explicit analytical form. It is shown that at high intensities when the ionization of the target material is complete before the end of the pulse, the ablation mechanism is the same for both metals and dielectrics. The physics of this new ablation regime involves ion acceleration in the electrostatic field caused by charge separation created by energetic electrons escaping from the target. The formulae ...

  13. 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.

  14. 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.

  15. 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.

  16. 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...

  17. Radiofrequency ablation of atrial fibrillation

    NARCIS (Netherlands)

    Wiesfeld, ACP; Tan, ES; Van Veldhuisen, DJ; Crijns, HJGM; Van Gelder, IC


    Twenty-five patients (16 males, mean age 46 years.) underwent radiofrequency ablation because of either paroxysmal (13 patients) or persistent atrial fibrillation (12 patients). Ablation aimed at earliest activation of spontaneous and catheter-induced repetitive ectopy in left and right atria and ap

  18. Laser ablation in analytical chemistry. (United States)

    Russo, Richard E; Mao, Xianglei; Gonzalez, Jhanis J; Zorba, Vassilia; Yoo, Jong


    In 2002, we wrote an Analytical Chemistry feature article describing the Physics of Laser Ablation in Microchemical Analysis. In line with the theme of the 2002 article, this manuscript discusses current issues in fundamental research, applications based on detecting photons at the ablation site (LIBS and LAMIS) and by collecting particles for excitation in a secondary source (ICP), and directions for the technology.

  19. Radiofrequency ablation of osteoid osteoma

    NARCIS (Netherlands)

    Vanderschueren, Geert Maria Joris Michael


    The main purpose of this thesis was to evaluate the effectiveness and safety of CT-guided radiofrequency ablation for the treatment of spinal and non-spinal osteoid osteomas. Furthermore, the technical requirements needed for safe radiofrequency ablation and the clinical outcome after radiofrequency

  20. 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...

  2. The physical and chemical structure of Sagittarius B2. II. Continuum millimeter emission of Sgr B2(M) and Sgr B2(N) with ALMA (United States)

    Sánchez-Monge, Á.; Schilke, P.; Schmiedeke, A.; Ginsburg, A.; Cesaroni, R.; Lis, D. C.; Qin, S.-L.; Müller, H. S. P.; Bergin, E.; Comito, C.; Möller, Th.


    Context. The two hot molecular cores Sgr B2(M) and Sgr B2(N), which are located at the center of the giant molecular cloud complex Sagittarius B2, have been the targets of numerous spectral line surveys, revealing a rich and complex chemistry. Aims: We seek to characterize the physical and chemical structure of the two high-mass star-forming sites Sgr B2(M) and Sgr B2(N) using high-angular resolution observations at millimeter wavelengths, reaching spatial scales of about 4000 au. Methods: We used the Atacama Large Millimeter/submillimeter Array (ALMA) to perform an unbiased spectral line survey of both regions in the ALMA band 6 with a frequency coverage from 211 GHz to 275 GHz. The achieved angular resolution is 0.̋4, which probes spatial scales of about 4000 au, i.e., able to resolve different cores and fragments. In order to determine the continuum emission in these line-rich sources, we used a new statistical method, STATCONT, which has been applied successfully to this and other ALMA datasets and to synthetic observations. Results: We detect 27 continuum sources in Sgr B2(M) and 20 sources in Sgr B2(N). We study the continuum emission variation across the ALMA band 6 (i.e., spectral index) and compare the ALMA 1.3 mm continuum emission with previous SMA 345 GHz and VLA 40 GHz observations to study the nature of the sources detected. The brightest sources are dominated by (partially optically thick) dust emission, while there is an important degree of contamination from ionized gas free-free emission in weaker sources. While the total mass in Sgr B2(M) is distributed in many fragments, most of the mass in Sgr B2(N) arises from a single object, with filamentary-like structures converging toward the center. There seems to be a lack of low-mass dense cores in both regions. We determine H2 volume densities for the cores of about 107-109 cm-3 (or 105-107 M⊙ pc-3), i.e., one to two orders of magnitude higher than the stellar densities of super star clusters. We

  3. Simulation of Pellet Ablation (United States)

    Parks, P. B.; Ishizaki, Ryuichi


    In order to clarify the structure of the ablation flow, 2D simulation is carried out with a fluid code solving temporal evolution of MHD equations. The code includes electrostatic sheath effect at the cloud interface.(P.B. Parks et al.), Plasma Phys. Contr. Fusion 38, 571 (1996). An Eulerian cylindrical coordinate system (r,z) is used with z in a spherical pellet. The code uses the Cubic-Interpolated Psudoparticle (CIP) method(H. Takewaki and T. Yabe, J. Comput. Phys. 70), 355 (1987). that divides the fluid equations into non-advection and advection phases. The most essential element of the CIP method is in calculation of the advection phase. In this phase, a cubic interpolated spatial profile is shifted in space according to the total derivative equations, similarly to a particle scheme. Since the profile is interpolated by using the value and the spatial derivative value at each grid point, there is no numerical oscillation in space, that often appears in conventional spline interpolation. A free boundary condition is used in the code. The possibility of a stationary shock will also be shown in the presentation because the supersonic ablation flow across the magnetic field is impeded.

  4. Bispecific antibody to ErbB2 overcomes trastuzumab resistance through comprehensive blockade of ErbB2 heterodimerization. (United States)

    Li, Bohua; Meng, Yanchun; Zheng, Lei; Zhang, Xunmin; Tong, Qing; Tan, Wenlong; Hu, Shi; Li, Hui; Chen, Yang; Song, Jinjing; Zhang, Ge; Zhao, Lei; Zhang, Dapeng; Hou, Sheng; Qian, Weizhu; Guo, Yajun


    The anti-ErbB2 antibody trastuzumab has shown significant clinical benefits in metastatic breast cancer. However, resistance to trastuzumab is common. Heterodimerization between ErbB2 and other ErbBs may redundantly trigger cell proliferation signals and confer trastuzumab resistance. Here, we developed a bispecific anti-ErbB2 antibody using trastuzumab and pertuzumab, another ErbB2-specific humanized antibody that binds to a distinct epitope from trastuzumab. This bispecific antibody, denoted as TPL, retained the full binding activities of both parental antibodies and exhibited pharmacokinetic properties similar to those of a conventional immunoglobulin G molecule. Unexpectedly, TPL showed superior ErbB2 heterodimerization-blocking activity over the combination of both parental monoclonal antibodies, possibly through steric hindrance and/or inducing ErbB2 conformational change. Further data indicated that TPL potently abrogated ErbB2 signaling in trastuzumab-resistant breast cancer cell lines. In addition, we showed that TPL was far more effective than trastuzumab plus pertuzumab in inhibiting the growth of trastuzumab-resistant breast cancer cell lines, both in vitro and in vivo. Importantly, TPL treatment eradicated established trastuzumab-resistant tumors in tumor-bearing nude mice. Our results suggest that trastuzumab-resistant breast tumors remain dependent on ErbB2 signaling and that comprehensive blockade of ErbB2 heterodimerization may be an effective therapeutic avenue. The unique potential of TPL to overcome trastuzumab resistance warrants its consideration as a promising treatment in the clinic.

  5. 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

  6. VEGFR1-mediated pericyte ablation links VEGF and PlGF to cancer-associated retinopathy

    DEFF Research Database (Denmark)

    Cao, Renhai; Xue, Yuan; Hedlund, Eva-Maria


    , and adenoviral vectors ablates pericytes from the mature retinal vasculature through the VEGF receptor 1 (VEGFR1)-mediated signaling pathway, leading to increased vascular leakage. In contrast, we demonstrate VEGF receptor 2 (VEGFR2) is primarily expressed in nonvascular photoreceptors and ganglion cells...

  7. 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...

  8. Dust emission in the Sagittarius B2 molecular cloud core (United States)

    Lis, Dariusz C.; Goldsmith, Paul F.


    A model is presented for the dust emission from the Sagittarius B2 molecular cloud core which reproduces the observed spectrum between 30 and 1300 micron, as well as the distribution of the emission at 1300 micron. The model is based on the assumption that Sgr B2(N) continuum source is located behind the dust cloud associated with Sgr B2(M) continuum source. The fact that Sgr B2(N) is stronger at 1300 micron can be attributed to a local column density maximum at the position of this source. Absence of a 53 micron emission peak at the position of Sgr B2(N) suggests that the luminosity of the north source is lower than that of the middle source.

  9. 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.

  10. 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.

  11. Magnetic and robotic navigation for catheter ablation: "joystick ablation". (United States)

    Ernst, Sabine


    Catheter ablation has become the treatment of choice to cure various arrhythmias in the last decades. The newest advancement of this general concept is made on the navigation ability using remote-controlled ablation catheters. This review summarizes the concept of the two currently available systems, followed by a critical review of the published clinical reports for each system, respectively. Despite the limited amount of data, an attempt to compare the two systems is made.

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

    Institute of Scientific and Technical Information of China (English)




  13. The physical and chemical structure of Sagittarius B2. II. Continuum millimeter emission of SgrB2(M) and SgrB2(N) with ALMA


    Sanchez-Monge, A.; Schilke, P.; Schmiedeke, A.; Ginsburg, A.; Cesaroni, R.; Lis, D. C.; Qin, S. -L.; Mueller, H. S. P.; Bergin, E.; Comito, C.; Moeller, Th.


    The high-mass star forming sites SgrB2(M) and SgrB2(N) have been the target of numerous studies, revealing e.g. a rich chemistry. We want to characterize their physical and chemical structure using ALMA high-angular resolution observations at mm wavelengths, reaching spatial scales of about 4000 au, and covering the whole band 6 (from 211 to 275 GHz). In order to determine the continuum emission in line-rich sources, we use a new statistical method: STATCONT. We detect 27 continuum sources in...

  14. 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.

  15. 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...

  16. 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.

  17. Continuum radiative transfer Modeling of Sagittarius B2


    Schmiedeke, A.; Schilke, P.; Möller, Th.; Sánchez-Monge, Á.; Bergin, E.; Comito, C.; Csengeri, T.; Lis, D. C.; Molinari, S.; Qin, S.L.; Rolffs, R.


    We present results from radiative transfer modeling of the continuum emission towards Sagittarius B2 (hereafter Sgr B2). We have developed a radiative transfer framework – Pandora – that employs RADMC-3D (Dullemond 2012) for a self-consistent determination of the dust temperature. With this pipeline, we have set-up a single model that consistently reproduces the thermal dust and free-free continuum emission of Sgr B2 spanning four orders of magnitude in spatial scales (0.02–45 pc) and two ord...

  18. 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。

  19. ErbB3 ablation impairs phosphatidylinositol 3-kinase (PI3K)/AKT-dependent mammary tumorigenesis (United States)

    Cook, Rebecca S.; Garrett, Joan T.; Sánchez, Violeta; Stanford, Jamie C.; Young, Christian; Chakravarty, Anindita; Rinehart, Cammie; Zhang, Yixian; Wu, Yaming; Greenberger, Lee; Horak, Ivan D.; Arteaga, Carlos L.


    Summary The ErbB receptor family member ErbB3 has been implicated in breast cancer growth but it has yet to be determined whether its disruption is therapeutically valuable. In a mouse model of mammary carcinoma driven by the polyomavirus middle T (PyVmT) oncogene, the ErbB2 tyrosine kinase inhibitor lapatinib reduced the activation of ErbB3 and Akt along with tumor cell growth. In this phosphatidylinositol-3 kinase (PI3K)-dependent tumor model, ErbB2 is part of a complex containing PyVmT, p85 (PI3K), ErbB3, and Src, that is disrupted by treatment with lapatinib. Thus, full engagement of PI3K/Akt by ErbB2 in this oncogene-induced mouse tumor model may involve its ability to dimerize with and phosphorylate ErbB3, which itself directly binds PI3K. Here we report that ErbB3 is critical for PI3K/AKT-driven tumor formation triggered by the PyVmT oncogene. Tissue-specific, Cre-mediated deletion of ErbB3 reduced Akt phosphorylation, primary tumor growth and pulmonary metastasis. Further EZN-3920, a chemically stabilized antisense oligonucleotide that targets the ErbB3 mRNA in vivo, produced similar effects while causing no mouse toxicity. Our findings offer further preclinical evidence that ErbB3 ablation may be therapeutically effective in tumors where ErbB3 engages PI3K/Akt signaling. PMID:21482676

  20. Field enhancement induced laser ablation

    DEFF Research Database (Denmark)

    Fiutowski, Jacek; Maibohm, Christian; Kjelstrup-Hansen, Jakob

    Sub-diffraction spatially resolved, quantitative mapping of strongly localized field intensity enhancement on gold nanostructures via laser ablation of polymer thin films is reported. Illumination using a femtosecond laser scanning microscope excites surface plasmons in the nanostructures...

  1. Ablative Approaches for Pulmonary Metastases. (United States)

    Boyer, Matthew J; Ricardi, Umberto; Ball, David; Salama, Joseph K


    Pulmonary metastases are common in patients with cancer for which surgery is considered a standard approach in appropriately selected patients. A number of patients are not candidates for surgery due to a medical comorbidities or the extent of surgery required. For these patients, noninvasive or minimally invasive approaches to ablate pulmonary metastases are potential treatment strategies. This article summarizes the rationale and outcomes for non-surgical treatment approaches, including radiotherapy, radiofrequency and microwave ablation, for pulmonary metastases.

  2. Radiofrequency Ablation in Barrett's Esophagus

    Directory of Open Access Journals (Sweden)

    Vani J.A. Konda


    Full Text Available Radiofrequency ablation (RFA is an endoscopic modality used in the treatment of Barrett's esophagus. RFA may be performed using a balloon-based catheter or using one of the probe catheters that attaches to the distal end of the endoscope. Here we demonstrate step-by-step instruction in using radiofrequency ablation in the treatment of Barrett's esophagus and highlight key concepts in the technique.

  3. 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.

  4. 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,...

  5. 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

  6. 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.

  7. 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 ...

  8. 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....

  9. 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.

  10. Atrial fibrillation ablation using a closed irrigation radiofrequency ablation catheter. (United States)

    Golden, Keith; Mounsey, John Paul; Chung, Eugene; Roomiani, Pahresah; Morse, Michael Andew; Patel, Ankit; Gehi, Anil


    Catheter ablation is an effective therapy for symptomatic, medically refractory atrial fibrillation (AF). Open-irrigated radiofrequency (RF) ablation catheters produce transmural lesions at the cost of increased fluid delivery. In vivo models suggest closed-irrigated RF catheters create equivalent lesions, but clinical outcomes are limited. A cohort of 195 sequential patients with symptomatic AF underwent stepwise AF ablation (AFA) using a closed-irrigation ablation catheter. Recurrence of AF was monitored and outcomes were evaluated using Kaplan-Meier survival analysis and Cox proportional hazards models. Mean age was 59.0 years, 74.9% were male, 56.4% of patients were paroxysmal and mean duration of AF was 5.4 years. Patients had multiple comorbidities including hypertension (76.4%), tobacco abuse (42.1%), diabetes (17.4%), and obesity (mean body mass index 30.8). The median follow-up was 55.8 weeks. Overall event-free survival was 73.6% with one ablation and 77.4% after reablation (reablation rate was 8.7%). Median time to recurrence was 26.9 weeks. AF was more likely to recur in patients being treated with antiarrhythmic therapy at the time of last follow-up (recurrence rate 30.3% with antiarrhythmic drugs, 13.2% without antiarrhythmic drugs; hazard ratio [HR] 2.2, 95% confidence interval [CI] 1.1-4.4, P = 0.024) and in those with a history of AF greater than 2 years duration (HR 2.7, 95% CI 1.1-6.9, P = 0.038). Our study represents the largest cohort of patients receiving AFA with closed-irrigation ablation catheters. We demonstrate comparable outcomes to those previously reported in studies of open-irrigation ablation catheters. Given the theoretical benefits of a closed-irrigation system, a large head-to-head comparison using this catheter is warranted. ©2012, The Authors. Journal compilation ©2012 Wiley Periodicals, Inc.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. Esophageal papilloma: Flexible endoscopic ablation byradiofrequency

    Institute of Scientific and Technical Information of China (English)

    Gianmattia del Genio; Federica del Genio; Pietro Schettino; Paolo Limongelli; Salvatore Tolone; Luigi Brusciano; Manuela Avellino; Chiara Vitiello; Giovanni Docimo; Angelo Pezzullo; Ludovico Docimo


    Squamous papilloma of the esophagus is a rare benignlesion of the esophagus. Radiofrequency ablation is anestablished endoscopic technique for the eradication ofBarrett esophagus. No cases of endoscopic ablation ofesophageal papilloma by radiofrequency ablation (RFA)have been reported. We report a case of esophagealpapilloma successfully treated with a single sessionof radiofrequency ablation. Endoscopic ablation ofthe lesion was achieved by radiofrequency using anew catheter inserted through the working channelof endoscope. The esophageal ablated tissue wasremoved by a specifically designed cup. Completeablation was confirmed at 3 mo by endoscopy withbiopsies. This case supports feasibility and safety of asa new potential indication for BarrxTM RFA in patientswith esophageal papilloma.

  2. 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.

  3. 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.

  4. High angular resolution submillimeter observations of Sagittarius B2

    Energy Technology Data Exchange (ETDEWEB)

    Goldsmith, P.F.; Lis, D.C.; Hills, R.; Lasenby, J. (Five College Radio Astronomy Observatory, Amherst, MA (USA) Mullard Radio Astronomy Observatory, Cambridge (England))


    Continuum observations of the Sgr B2 molecular cloud have been carried out. The data offer the first detailed description of the submillimeter radiation from this complex source. The emission is dominated by the middle and northern compact sources, but the far-infrared radiation associated with the Northeast H II region L and from the southern H II region/molecular maser source H have been detected for the first time. The data, together with existing infrared measurements, indicate that the optical depth within Sgr B2(N) is significantly greater than that of Sgr B2(M) and that it has a noticeable effect for lambda = 800 microns or less. The envelope of Sgr B2(M) becomes optically thick for the radiation from Sgr B2(N), located within it, for wavelengths 100 microns or less. From radiative transfer modeling, a luminosity of 10 million solar is obtained for the middle source and 2 million solar for the northern source. 30 refs.

  5. 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 ...

  6. Femtosecond laser ablation of enamel (United States)

    Le, Quang-Tri; Bertrand, Caroline; Vilar, Rui


    The surface topographical, compositional, and structural modifications induced in human enamel by femtosecond laser ablation is studied. The laser treatments were performed using a Yb:KYW chirped-pulse-regenerative amplification laser system (560 fs and 1030 nm) and fluences up to 14 J/cm2. The ablation surfaces were studied by scanning electron microscopy, grazing incidence x-ray diffraction, and micro-Raman spectroscopy. Regardless of the fluence, the ablation surfaces were covered by a layer of resolidified material, indicating that ablation is accompanied by melting of hydroxyapatite. This layer presented pores and exploded gas bubbles, created by the release of gaseous decomposition products of hydroxyapatite (CO2 and H2O) within the liquid phase. In the specimen treated with 1-kHz repetition frequency and 14 J/cm2, thickness of the resolidified material is in the range of 300 to 900 nm. The micro-Raman analysis revealed that the resolidified material contains amorphous calcium phosphate, while grazing incidence x-ray diffraction analysis allowed detecting traces of a calcium phosphate other than hydroxyapatite, probably β-tricalcium phosphate Ca3), at the surface of this specimen. The present results show that the ablation of enamel involves melting of enamel's hydroxyapatite, but the thickness of the altered layer is very small and thermal damage of the remaining material is negligible.

  7. 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.

  8. 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...

  9. 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.

  10. Applying conceptual design to B2B sales negotiations

    DEFF Research Database (Denmark)

    Illi, Mikko; Ylirisku, Salu

    sales agent’s work practice and collaborative conceptual design work, i.e. innovation design work. This perception provides a means to understand the value that the use of conceptual design tools could possibly provide for sales negotiation work. We also use the notion of boundary object to elaborate......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...

  11. Excitation, abundance, and distribution of HNCO in Sagittarius B2

    Energy Technology Data Exchange (ETDEWEB)

    Churchwell, E.; Wood, D.; Myers, P.C.; Myers, R.V.


    Snyder and Buhl (1972) have discovered isocyanic acid (HNCO) in Sgr B2. It is pointed out that HNCO is a particularly interesting interstellar molecule because under certain conditions it can be employed in a study of the far-infrared radiation field of the cloud in which it resides. The present study was mainly conducted with the aim to establish empirically the extent to which HNCO is populated by radiative processes in a source with a measured far-infrared radiation field. It is attempted to deduce the radiation field from the HNCO excitation conditions. Attention is given to an energy-level diagram of HNCO in the ground electronic and vibrational states, the antenna and receiver properties, a table with the observed parameters toward Sagittarius B2, the velocity structure, the HNCO intensity distribution, a summary of the Sgr B2 properties, the population distribution and column density, and the excitation of HNCO. 27 references.

  12. Neutron scattering studies of superconducting MgB2 tapes (United States)

    Bellingeri, E.; Malagoli, A.; Modica, M.; Braccini, V.; Siri, A. S.; Grasso, G.


    The capability of manufacturing long superconducting MgB2 wires with already remarkable critical currents makes this material a very promising candidate for future applications. Tapes are prepared by the powder-in-tube technique. After the cold working procedure typically carried out by wire drawing and cold rolling, it has been found that a final sintering step carried out in argon atmosphere is a key process for further improving the superconducting properties of the conductors. To study the effect of the deformation and heat treatment processes, we performed neutron scattering experiment. Due to the high penetration depth of neutron inside matter, it was possible to analyse the MgB2 phase still wrapped in the Ni sheath. Our studies were carried out by a full spectra refinement by the Rietveld method. In the starting superconducting powder a large Mg deficiency was observed. In the tapes we found that the large forces applied during the cold working induced a large MgB2 lattice deformation, and that it is partly relaxed during the final sintering process. An important correlation of the residual stress with the critical temperature and the pinning properties was pointed out. We also observed the appearance of detrimental secondary phases during the sintering process. In particular, the MgB2 phase reacted with the nickel sheath and MgB2Ni2.5 was formed at temperatures higher than 850 °C. These results are of basic importance for a further optimization of the transport properties at moderate fields where applications of MgB2 tapes are already envisageable.

  13. 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.

  14. 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.

  15. 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.

  16. Development of New B2B Venture Corporate Brand Identity

    DEFF Research Database (Denmark)

    Törmälä, Minna; Gyrd-Jones, Richard I.


    The development and role of brand identity in new B2B ventures is not well explored despite the challenge for such organisations in establishing reputational legitimacy. Previous research defines corporate brand identity as stable and endogenous to the organisation based either on the reputational...... of interviews and archival data generated during a three-year period to examine the development of corporate brand over time. This study shows that the development of corporate brand identity and the context of the development of new B2B venture are closely intertwined processes and provides a framework...

  17. 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.

  18. 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.

  19. 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...

  20. Water Masers in W49 North and Sagittarius B2


    McGrath, E. J.; Goss, W. M.; De Pree, C. G.


    Using the Very Large Array (VLA) of the National Radio Astronomy Observatory in the A and B configurations, we have obtained simultaneous high resolution observations of both the 22 GHz water maser lines as well as the 22 GHz continuum for the H II regions W49N and Sagittarius B2. The angular resolution of both observations is ~0.1", which at the distance of W49N (11.4 kpc; Gwinn, Moran, & Reid 1992) and Sgr B2 (8.5 kpc) corresponds to a physical size of

  1. 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.

  2. Laser ablation studies of nanocomposites

    Directory of Open Access Journals (Sweden)

    Oleg V. Mkrtychev


    Full Text Available The first experimental measurements of the threshold energy density values for the laser ablation of glass nanocomposites with nanodimensional coatings have been carried out under the action of the YAG–Nd laser power pulse radiation. The coatings in question were of different compositions and had been created by the sol–gel technology. The procedure for determining the laser ablation threshold energy density values was worked out on the base of the breakdown probability level of 0.5. The statistical processing of the measurement data over all the samples allowed obtaining the dependence of the ablation destruction threshold energy parameters on the coating physical and chemical properties such as the sample transmission in the visible region of the spectrum, coating thickness, the chemical composition of the film-forming solution, and on the pulse duration of laser radiation.

  3. Microwave ablation of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)


    Although surgical resection is still the optimal treatmentoption for early-stage hepatocellular carcinoma(HCC) in patients with well compensated cirrhosis,thermal ablation techniques provide a valid nonsurgicaltreatment alternative, thanks to their minimalinvasiveness, excellent tolerability and safety profile,proven efficacy in local disease control, virtuallyunlimited repeatability and cost-effectiveness. Differentenergy sources are currently employed in clinics asphysical agents for percutaneous or intra-surgicalthermal ablation of HCC nodules. Among them, radiofrequency(RF) currents are the most used, whilemicrowave ablations (MWA) are becoming increasinglypopular. Starting from the 90s', RF ablation (RFA) rapidlybecame the standard of care in ablation, especially inthe treatment of small HCC nodules; however, RFAexhibits substantial performance limitations in thetreatment of large lesions and/or tumors located nearmajor heat sinks. MWA, first introduced in the FarEastern clinical practice in the 80s', showing promisingresults but also severe limitations in the controllabilityof the emitted field and in the high amount of poweremployed for the ablation of large tumors, resultingin a poor coagulative performance and a relativelyhigh complication rate, nowadays shows better resultsboth in terms of treatment controllability and of overallcoagulative performance, thanks to the improvementof technology. In this review we provide an extensiveand detailed overview of the key physical and technicalaspects of MWA and of the currently available systems,and we want to discuss the most relevant published dataon MWA treatments of HCC nodules in regard to clinicalresults and to the type and rate of complications, both inabsolute terms and in comparison with RFA.

  4. Transhemangioma Ablation of Hepatocellular Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Pua, Uei, E-mail: [Tan Tock Seng Hospital, Department of Diagnostic Radiology (Singapore)


    Radiofrequency ablation (RFA) is a well-established treatment modality in the treatment of early hepatocellular carcinoma (HCC) [1]. Safe trajectory of the RFA probe is crucial in decreasing collateral tissue damage and unwarranted probe transgression. As a percutaneous technique, however, the trajectory of the needle is sometimes constrained by the available imaging plane. The presence of a hemangioma beside an HCC is uncommon but poses the question of safety related to probe transgression. We hereby describe a case of transhemangioma ablation of a dome HCC.

  5. Trigeminal nerve injury ErbB3/ErbB2 promotes mechanical hypersensitivity. (United States)

    Ma, Fei; Zhang, Liping; Westlund, Karin N


    Chronic constriction injury of the trigeminal infraorbital nerve results in transient analgesia followed by whisker pad mechanical allodynia in rats. Neuregulin 1 expressed on axonal membranes binds receptor tyrosine kinase ErbB, promoting Schwann cell development and remyelination. This study investigated whether orofacial mechanical allodynia is signaled by ErbB3-ErbB2 heterodimers in injured nerves. Whisker pad mechanical allodynia (von Frey stimuli) was quantified in wild type rats and in transgenic rats with Sleeping Beauty transposon mutation for neuregulin 1 transgene. Pain-related behavior was retested after intraperitoneal injection of the ErbB2 inhibitor Lapatinib, an agent shown by others to reduce breast cancer pain. Infraorbital nerve injury was evaluated histologically with myelin and neuronal biomarkers. ErbB3 changes over time were measured with western blots. Whisker pad mechanical hypersensitivity began in week 2 in wild type rats (3.11 ± 5.93 g vs. 18.72 ± 0.00 g after sham surgery, n = 9, P wild type rats was alleviated by Lapatinib (15 ± 3.89 g vs. 2.45 ± 1.13 g, n = 6, P wild type and transgenic rats (week 10) coincided with time points when mechanical hypersensitivity was present. The Neuregulin 1-ErbB3-ErbB2 complex is a causal mechanism in nerve injury-induced trigeminal neuropathic pain. Understanding peripheral glial mechanisms after nerve injury will improve neuropathic pain treatment.

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

    DEFF Research Database (Denmark)

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


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

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

    Directory of Open Access Journals (Sweden)

    Pierluigi Sabbatini


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

  8. Molecular line survey of Sagittarius B2(M) from 330 to 355 GHz and comparison with Sagittarius B2(N) (United States)

    Sutton, E. C.; Jaminet, P. A.; Danchi, W. C.; Blake, Geoffrey A.


    A submillimeter survey of Sgr B2 is described in which sufficient spatial resolution permitted the observation of some of the source structure. The position Sgr B2(M) is examined in relation to the submillimeter emission of Sgr B2(N) and previous millimeter observational data of source (M) at a lower spatial resolution. Because the submillimeter observations are more sensitive to core emission, the molecules SO2 and CH3OH tend to dominate the spectrum. The core emission is found to be similar to that of the Orion molecular cloud, and the submillimeter and millimeter lines have high optical depths. The (N) source has a much higher column density than that of (M) except for SO and SO2, and (N) also appears to have a higher excitation which can indicate a core with a higher density.

  9. Ablation of Solid Hydrogen in a Plasma

    DEFF Research Database (Denmark)

    Jørgensen, L. W.; Sillesen, Alfred Hegaard


    Several hydrogen pellet ablation models based on the formation of a shielding neutral cloud have been reported by different authors. The predicted ablation rates are shown to follow almost the same scaling law and this is used to explain the authors' ablation experiment....

  10. Soft thrombus formation in radiofrequency catheter ablation

    NARCIS (Netherlands)

    Demolin, JM; Eick, OJ; Munch, K; Koullick, E; Nakagawa, H; Wittkampf, FHM


    During RF catheter ablation, local temperature elevation can result in coagulum formation on the ablation electrode, resulting in impedance rise. A recent study has also demonstrated the formation of a so-called soft thrombus during experimental ablations. This deposit poorly adhered to the catheter

  11. Catheter ablation of parahisian premature ventricular complex. (United States)

    Kim, Jun; Kim, Jeong Su; Park, Yong Hyun; Kim, June Hong; Chun, Kook Jin


    Catheter ablation is performed in selected patients with a symptomatic premature ventricular complex (PVC) or PVC-induced cardiomyopathy. Ablation of PVC from the His region has a high risk of inducing a complete atrioventricular block. Here we report successful catheter ablation of a parahisian PVC in a 63-year-old man.

  12. Laser ablation at the hydrodynamic regime

    Directory of Open Access Journals (Sweden)

    Gojani Ardian B.


    Full Text Available Laser ablation of several metals and PVC polymer by high energy nanosecond laser pulses is investigated experimentaly. Visualization by shadowgraphy revealed the dynamics of the discontinuities in ambient air and ablation plume above the target surface, while surface profiling allowed for determination of the ablated mass.

  13. Laser ablation at the hydrodynamic regime


    Gojani Ardian B.


    Laser ablation of several metals and PVC polymer by high energy nanosecond laser pulses is investigated experimentaly. Visualization by shadowgraphy revealed the dynamics of the discontinuities in ambient air and ablation plume above the target surface, while surface profiling allowed for determination of the ablated mass.

  14. Laser ablation and optical surface damage (United States)

    Chase, L. L.; Hamza, A. V.; Lee, H. W. H.

    Laser ablation usually accompanies optical surface damage to bare surfaces and coatings. Investigations of optical damage mechanisms by observation of ablation processes at laser fluences very close to the optical damage threshold are described. Several promising surface characterization methods for investigating damage mechanisms are also described. The possible role of laser ablation in initiating or promoting optical surface damage is discussed.

  15. Laser ablation mechanisms and optical surface damage (United States)

    Chase, L. L.; Hamza, A. V.; Lee, H. W. H.


    Laser ablation usually accompanies optical surface damage to bare surfaces and coatings. Investigations of optical damage mechanisms by observation of ablation processes at laser fluences very close to the optical damage threshold are described. Several promising surface characterization methods for investigating damage mechanisms are also described. The possible role of laser ablation in initiating or promoting optical surface damage is discussed.

  16. 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...

  17. 26 CFR 53.4942(b)-2 - Alternative tests. (United States)


    ... facilities), and intangible assets (such as patents, copyrights, and trademarks) will be considered... disbursements method of accounting. For 1971, the fair market value of X's assets not described in paragraph (c....4942(b)-2 Alternative tests. (a) Assets test—(1) In general. A private foundation will satisfy the...

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. 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

  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. 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

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

    NARCIS (Netherlands)

    Comito, C.; Schilke, P.; Rolffs, R.; 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.; Müller, H. S. P.; Murphy, J. A.; Neufeld, D. A.; Ossenkopf, V.; Pearson, J. C.; Pérault, 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

  6. Laser cladding of aluminium using TiB2

    CSIR Research Space (South Africa)

    Kumar, S


    Full Text Available - erties of the boride layers laser fabricated on Ti-6Al-4V al- loy. Journal of Materials Pro- cessing Technology, 209, 2887- 2891. [7] Abboud, J. H. and West, D. R. F. (1994) Microstructure of Ti-TiB2 surface layers pro- duced by laser particle...

  7. Cyanodiacetylene (HC/sub 5/N) in Sagittarius B2

    Energy Technology Data Exchange (ETDEWEB)

    Avery, L.W.; Oka, T.; Broten, N.W.; MacLeod, J.M.


    The J=2..-->..1 and 3..-->..2 rotational transitions of cyanodiacetylene have been observed in Sgr B2. Statistical equilibrium calculations have been carried out to construct a three-component model of the HC/sub 5/N cloud in Sgr B2 which is consistent with these observations, with our earlier observations of the J=1..-->..0.4..-->..3, and 8..-->..7 lines and with the data obtained by Guelin and Thaddeus for the J=31..-->..30 to J=37..-->..36 millimeter-wave transitions. The relative strength of the J=1..-->..0 line requires the presence of an extensive, low-density envelope around the Sgr B2 molecular cloud which serves as a weak 1..-->..0 line maser. This envelope is characterized by an H/sub 2/ density of 100 cm/sup -3/ and a kinetic temperature of about 20 K. The maximum column density of HC/sub 5/N in Sgr B2 is found to be 1.6 x 10/sup 14/ cm/sup -3/, equal to that of HC/sub 3/N.

  8. 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

  9. Nanosecond laser ablation of bulk Al, Bronze, and Cu: ablation rate saturation and laserinduced oxidation


    R. Maisterrena-Epstein; S. Camacho-López; L. Escobar-Alarcón; M. A. Camacho-López


    In this work we report about the characteristics of nanosecond laser ablation, in atmospheric air, of bulk Al, Bronze, and Cu. Average per pulse laser ablation rate and its dependence on ablation depth is presented for these three metals. We will demonstrate and discuss some distinctive features of the ablation saturation effect of the above metals. We will also present results on laser-induced oxidation of the metals which results off the ablation event. We studied the laser-induced oxidatio...

  10. 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

  11. Photochemical Ablation of Organic Solids (United States)

    Garrison, Barbara


    As discovered by Srinivasan in 1982, irradiation of materials by far UV laser light can lead to photochemical ablation, a process distinct from normal thermal ablation in which the laser primarily heats the material. A versatile mesoscopic model for molecular dynamics simulations of the laser ablation phenomena is presented. The model incorporates both the thermal and photochemical events, that is, both heating of the system and UV induced bond-cleavage followed by abstraction and radical-radical recombination reactions. The results from the simulations are compared to experimental data and the basic physics and chemistry for each irradiation regime are discussed. Initial results from polymer ablation simulations will be presented. L. V. Zhigilei, P. B. S. Kodali and B. J. Garrison, J. Phys. Chem. B, 102, 2845-2853 (1998); L. V. Zhigilei and B. J. Garrison, Journal of Applied Physics, 88, 1281-1298 (2000). Y. G. Yingling, L. V. Zhigilei and B. J. Garrison, J. Photochemistry and Photobiology A: Chemistry, 145, 173-181 (2001); Y. G. Yingling and B. J. Garrison, Chem. Phys. Lett., 364, 237-243 (2002).

  12. Catheter ablation - new developments in robotics. (United States)

    Chun, K R Julian; Schmidt, Boris; Köktürk, Bülent; Tilz, Roland; Fürnkranz, Alexander; Konstantinidou, Melanie; Wissner, Erik; Metzner, Andreas; Ouyang, Feifan; Kuck, Karl-Heinz


    Catheter ablation has become the curative treatment modality for various arrhythmias. Extending the indications for catheter ablation from simple supraventricular tachycardias to complex arrhythmias such as ventricular tachycardia or atrial fibrillation, the investigator faces prolonged procedure times, fluoroscopy exposure and the need for stable and reproducible catheter movement. Recently, remote-controlled robotic catheter ablation has emerged as a novel ablation concept to meet these requirements. This review describes the two available robotic ablation systems and summarizes their clinical applications and current human experience.

  13. Hydrodynamic instabilities in an ablation front

    Energy Technology Data Exchange (ETDEWEB)

    Piriz, A R; Portugues, R F [E.T.S.I. Industriales, Universidad de Castilla-La Mancha, 13071 Ciudad Real (Spain)


    The hydrodynamic stability of an ablation front is studied for situations in which the wavelength of the perturbations is larger than the distance to the critical surface where the driving radiation is absorbed. An analytical model is presented, and it shows that under conditions in which the thermal flux is limited within the supercritical region of the ablative corona, the front may behave like a flame or like an ablation front, depending on the perturbation wavelength. For relatively long wavelengths the critical and ablation surfaces practically lump together into a unique surface and the front behaves like a flame, whereas for the shortest wavelengths the ablation front substructure is resolved.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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...

  1. 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.

  2. 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.

  3. 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.

  4. 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....

  5. 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.

  6. 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...

  7. 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...

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. Strength anomaly in B2 FeAl single crystals

    Energy Technology Data Exchange (ETDEWEB)

    Yoshimi, K.; Hanada, S.; Yoo, M.H. [Oak Ridge National Lab., TN (United States); Matsumoto, N. [Tohoku Univ. (Japan). Graduate School


    Strength and deformation microstructure of B2 Fe-39 and 48%Al single crystals (composition given in atomic percent), which were fully annealed to remove frozen-in vacancies, have been investigated at temperatures between room temperature and 1073K. The hardness of as-homogenized Fe-48Al is higher than that of as-homogenized Fe-39Al while after additional annealing at 698K the hardness of Fe-48Al becomes lower than that of Fe-39Al. Fe-39Al single crystals slowly cooled after homogenizing at a high temperature were deformed in compression as a function of temperature and crystal orientation. A peak of yield strength appears around 0.5T{sub m} (T{sub m} = melting temperature). The orientation dependence of the critical resolved shear stress does not obey Schmid`s law even at room temperature and is quite different from that of b.c.c. metals and B2 intermetallics at low temperatures. At the peak temperature slip transition from <111>-type to <001>-type is found to occur macroscopically and microscopically, while it is observed in TEM that some of the [111] dislocations decompose into [101] and [010] on the (1096I) plane below the peak temperature. The physical sources for the positive temperature dependence of yield stress of B2 FeAl are discussed based on the obtained results.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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...

  18. Glue septal ablation: A promising alternative to alcohol septal ablation

    Directory of Open Access Journals (Sweden)

    Sercan Okutucu


    Full Text Available Hypertrophic cardiomyopathy (HCM is defined as myocardial hypertrophy in the absence of another cardiac or systemic disease capable of producing the magnitude of present hypertrophy. In about 70% of patients with HCM, there is left ventricular outflow tract (LVOT obstruction (LVOTO and this is known as obstructive type of hypertrophic cardiomyopathy (HOCM. Cases refractory to medical treatment have had two options either surgical septal myectomy or alcohol septal ablation (ASA to alleviate LVOT gradient. ASA may cause some life-threatening complications including conduction disturbances and complete heart block, hemodynamic compromise, ventricular arrhythmias, distant and massive myocardial necrosis. Glue septal ablation (GSA is a promising technique for the treatment of HOCM. Glue seems to be superior to alcohol due to some intrinsic advantageous properties of glue such as immediate polymerization which prevents the leak into the left anterior descending coronary artery and it is particularly useful in patients with collaterals to the right coronary artery in whom alcohol ablation is contraindicated. In our experience, GSA is effective and also a safe technique without significant complications. GSA decreases LVOT gradient immediately after the procedure and this reduction persists during 12 months of follow-up. It improves New York Heart Association functional capacity and decrease interventricular septal wall thickness. Further studies are needed in order to assess the long-term efficacy and safety of this technique.

  19. 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).

  20. Laser Ablation Propulsion A Study (United States)

    Irfan, Sayed A.; Ugalatad, Akshata C.

    Laser Ablation Propulsion (LAP) will serve as an alternative propulsion system for development of microthrusters. The principle of LAP is that when a laser (pulsed or continuous wave) with sufficient energy (more than the vaporization threshold energy of material) is incident on material, ablation or vaporization takes place which leads to the generation of plasma. The generated plasma has the property to move away from the material hence pressure is generated which leads to the generation of thrust. Nowadays nano satellites are very common in different space and defence applications. It is important to build micro thruster which are useful for orienting and re-positioning small aircraft (like nano satellites) above the atmosphere. modelling of LAP using MATLAB and Mathematica. Schematic is made for the suitable optical configuration of LAP. Practical experiments with shadowgraphy and self emission techniques and the results obtained are analysed taking poly (vinyl-chloride) (PVC) as propellant to study the

  1. 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.

  2. 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.

  3. 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)

  4. Shock wave consolidated MgB 2 bulk samples (United States)

    Matsuzawa, Hidenori; Tamaki, Hideyuki; Ohashi, Wataru; Kakimoto, Etsuji; Dohke, Kiyotaka; Atou, Toshiyuki; Fukuoka, Kiyoto; Kikuchi, Masae; Kawasaki, Masashi; Takano, Yoshihiko


    Commercially available MgB 2 powders were consolidated into bulk samples by two different shock wave consolidation methods: underwater shock consolidation method and gun method. Resistance vs. temperature of the samples was measured by the four-terminal method for pulsed currents of up to 3 A in self-field, as well as Vickers hardness, SEM micrographs of fraction surfaces, packing densities, and X-ray diffraction patterns. These results, in comparison with cold isostatic pressed samples, indicated that the underwater shock consolidated sample was superior in grain connectivity to the others. This is probably because the underwater shock consolidation generated most anisotropic and hence high frictional, compressive, intergrain forces.

  5. 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.

  6. Model for the radio source Sagittarius B2

    Energy Technology Data Exchange (ETDEWEB)

    Gosachinskii, I.; Khersonskii, V.


    A dynamical model is proposed for the gas cloud surrounding the radio source Sgr B2. The kinematic behavior of the gas in the source is interpreted in terms of a contracting core and a rotating outer envelope. The cloud initially would have been kept stable by turbulent motion, whose energy would be dissipated into heat by magnetic viscosity. This process should operate more rapidly in the dense core, which would begin to collapse while the envelope remains stable. The initial cloud parameters and various circumstances of the collapse are calculated, and estimates are obtained for the conditions in the core at the time of its fragmentation into clumps of stellar mass.

  7. Far-IR spectroscopy towards Sagittarius B2


    Goicoechea, Javier R.; Cernicharo, José


    The far-IR is a unique wavelength range for Astrophysical studies, however, it can only be fully sampled from space platforms. The fundamental rotational transitions of light molecules, the high-J transitions of polyatomic species, the bending modes of non-polar molecules, several atomic fine structure lines and many frequencies blocked by the earth atmosphere can only be observed between 50 and 200 um (6.0 and 1.5 THz). In this contribution we present the far-IR spectrum of Sgr B2 at a resol...

  8. Transient Ablation Regime in Circuit Breakers

    Institute of Scientific and Technical Information of China (English)

    Alexandre MARTIN; Jean-Yves TREPANIER; Marcelo REGGIO; GUO Xue-yan


    Nozzle wall ablation caused by high temperature electric arcs is studied in the context of high voltage SF6 circuit breakers.The simplified ablation model used in litterature has been updated to take into account the unsteady state of ablation.Ablation rate and velocity are now calculated by a kinetic model using two layers of transition,between the bulk plasma and the ablating wall.The first layer (Knudsen layer),right by the wall,is a kinetic layer of a few mean-free path of thickness.The second layer is collision dominated and makes the transition between the kinetic layer and the plasma bulk.With this new coupled algorithm,it is now possible to calculate the temperature distribution inside the wall,as well as more accurate ablation rates.

  9. c-erbB-2 protein overexpression and p53 immunoreaction in primary and recurrent breast cancer tissues. (United States)

    Shimizu, C; Fukutomi, T; Tsuda, H; Akashi-Tanaka, S; Watanabe, T; Nanasawa, T; Sugihara, K


    We investigated whether expression levels of c-erbB-2 and p53 proteins in breast cancer tissues differ in primary and metastatic lesions. Immunohistochemical staining or sandwich enzyme immunoassay was used to determine expression levels of c-erbB-2 and p53 proteins in 42 breast cancer samples from 21 patients. Estrogen (ER) and progesterone receptors (PgR) were also measured by enzyme immunoassay in each case. All patients had undergone radical surgery for primary tumors and surgical resection of asynchronous metastatic lesions. Thirteen patients (62%) were premenopausal and 14 (67%) received postoperative adjuvant therapies. Median disease-free survival time was 26 months (range, 5-104). The resected metastatic lesions included 1 in the liver, 3 in the lung, and 3 in the supraclavicular lymph nodes. The remaining 14 were local skin lesions. There was no difference in the positivity rate of c-erbB-2 (38%: 8/21) and p53 (39%: 7/18) expression between the primary tumors and the recurrent lesions. In addition, no discordant c-erbB-2 or p53 expression was observed between the primary tumors and their respective metastatic lesions. Positivity rates for ER and PgR were 50% (10/20) and 60% (12/20) for the primary tumors, but only 25% (5/20) and 30% (6/20) for the recurrent lesions, respectively (P = 0. 19 for ER and P = 0.11 for PgR). c-erbB-2 and p53 expression levels in breast cancer cells were almost unchanged as the disease progressed and/or in response to adjuvant therapies, regardless of the hormone receptor status. Copyright 2000 Wiley-Liss, Inc.

  10. Computer-aided hepatic tumour ablation

    CERN Document Server

    Voirin, D; Amavizca, M; Leroy, A; Letoublon, C; Troccaz, J; Voirin, David; Payan, Yohan; Amavizca, Miriam; Leroy, Antoine; Letoublon, Christian; Troccaz, Jocelyne


    Surgical resection of hepatic tumours is not always possible. Alternative techniques consist in locally using chemical or physical agents to destroy the tumour and this may be performed percutaneously. It requires a precise localisation of the tumour placement during ablation. Computer-assisted surgery tools may be used in conjunction to these new ablation techniques to improve the therapeutic efficiency whilst benefiting from minimal invasiveness. This communication introduces the principles of a system for computer-assisted hepatic tumour ablation.

  11. Neocuproine Ablates Melanocytes in Adult Zebrafish


    O'Reilly-Pol, Thomas; Johnson, Stephen L.


    The simplest regeneration experiments involve the ablation of a single cell type. While methods exist to ablate the melanocytes of the larval zebrafish,1,2 no convenient method exists to ablate melanocytes in adult zebrafish. Here, we show that the copper chelator neocuproine (NCP) causes fragmentation and disappearance of melanin in adult zebrafish melanocytes. Adult melanocytes expressing eGFP under the control of a melanocyte-specific promoter also lose eGFP fluorescence in the presence of...

  12. 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

  13. 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.


    Directory of Open Access Journals (Sweden)

    A. Jakimi


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

  15. 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.

  16. 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.

  17. 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.

  18. Low energy proton irradiation on MgB 2 bulk (United States)

    Mezzetti, E.; Botta, D.; Cherubini, R.; Chiodoni, A.; Gerbaldo, R.; Ghigo, G.; Giunchi, G.; Gozzelino, L.; Minetti, B.


    This paper studies the effects of defects induced by 6 MeV protons on high-density pellets of MgB 2. This methodology is useful to test the possibility to hinder the in-field decay of critical current density through extrinsic pinning centers as well as to check the radiation hardness of this material. Magnetic properties of two twin samples, the first one as-grown, the second one irradiated at a fluence of 0.8×10 16 p/cm 2 were measured and compared. The main outcome of the study is that this high-density material is quite hard with respect to irradiation with medium-energy proton beams. This makes MgB 2 a good candidate for out-space applications. However some little modulation, either damage or enhancement, of the magnetic properties is observed. The impact of the effect is not sufficient to prevent the in-field decay of the magnetization, although it presents some interesting characteristics worth to be discussed in a framework of comparison with analogous results on HTSC. In particular, the results suggest some correlation between defects along the beam path. The main open issue concerns the existence of “hidden weak links”, hinted by the field dependence of the high-temperature persisting damage.

  19. 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...

  20. 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.

  1. 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.

  2. Cryoballoon Catheter Ablation in Atrial Fibrillation

    Directory of Open Access Journals (Sweden)

    Cevher Ozcan


    Full Text Available Pulmonary vein isolation with catheter ablation is an effective treatment in patients with symptomatic atrial fibrillation refractory or intolerant to antiarrhythmic medications. The cryoballoon catheter was recently approved for this procedure. In this paper, the basics of cryothermal energy ablation are reviewed including its ability of creating homogenous lesion formation, minimal destruction to surrounding vasculature, preserved tissue integrity, and lower risk of thrombus formation. Also summarized here are the publications describing the clinical experience with the cryoballoon catheter ablation in both paroxysmal and persistent atrial fibrillation, its safety and efficacy, and discussions on the technical aspect of the cryoballoon ablation procedure.

  3. Aromatic Thermosetting Copolyesters for Ablative TPS Project (United States)

    National Aeronautics and Space Administration — Better performing ablative thermal protection systems than currently available are needed to satisfy requirements of the most severe crew exploration vehicles, such...

  4. The atrial fibrillation ablation pilot study

    DEFF Research Database (Denmark)

    Arbelo, Elena; Brugada, Josep; Hindricks, Gerhard


    AIMS: The Atrial Fibrillation Ablation Pilot Study is a prospective registry designed to describe the clinical epidemiology of patients undergoing an atrial fibrillation (AFib) ablation, and the diagnostic/therapeutic processes applied across Europe. The aims of the 1-year follow-up were to analyse...... tachycardia, and 4 patients died (1 haemorrhagic stroke, 1 ventricular fibrillation in a patient with ischaemic heart disease, 1 cancer, and 1 of unknown cause). CONCLUSION: The AFib Ablation Pilot Study provided crucial information on the epidemiology, management, and outcomes of catheter ablation of AFib...

  5. Femtosecond ultraviolet laser ablation of silver and comparison with nanosecond ablation

    DEFF Research Database (Denmark)

    Christensen, Bo Toftmann; Doggett, B.; Budtz-Jørgensen, C.


    The ablation plume dynamics arising from ablation of silver with a 500 fs, 248 nm laser at ~2 J cm-2 has been studied using angle-resolved Langmuir ion probe and thin film deposition techniques. For the same laser fluence, the time-of-flight ion signals from femtosecond and nanosecond laser ablat...

  6. Phase and Microstructural Correlation of Spark Plasma Sintered HfB2-ZrB2 Based Ultra-High Temperature Ceramic Composites

    Directory of Open Access Journals (Sweden)

    Ambreen Nisar


    Full Text Available The refractory diborides (HfB2 and ZrB2 are considered as promising ultra-high temperature ceramic (UHTCs where low damage tolerance limits their application for the thermal protection system in re-entry vehicles. In this regard, SiC and CNT have been synergistically added as the sintering aids and toughening agents in the spark plasma sintered (SPS HfB2-ZrB2 system. Herein, a novel equimolar composition of HfB2 and ZrB2 has shown to form a solid-solution which then allows compositional tailoring of mechanical properties (such as hardness, elastic modulus, and fracture toughness. The hardness of the processed composite is higher than the individual phase hardness up to 1.5 times, insinuating the synergy of SiC and CNT reinforcement in HfB2-ZrB2 composites. The enhanced fracture toughness of CNT reinforced composite (up to a 196% increment surpassing that of the parent materials (ZrB2/HfB2-SiC is attributed to the synergy of solid solution formation and enhanced densification (~99.5%. In addition, the reduction in the analytically quantified interfacial residual tensile stress with SiC and CNT reinforcements contribute to the enhancement in the fracture toughness of HfB2-ZrB2-SiC-CNT composites, mandatory for aerospace applications.

  7. 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

  8. Analysis of iodinated contrast delivered during thermal ablation: is material trapped in the ablation zone? (United States)

    Wu, Po-hung; Brace, Chris L.


    Intra-procedural contrast-enhanced CT (CECT) has been proposed to evaluate treatment efficacy of thermal ablation. We hypothesized that contrast material delivered concurrently with thermal ablation may become trapped in the ablation zone, and set out to determine whether such an effect would impact ablation visualization. CECT images were acquired during microwave ablation in normal porcine liver with: (A) normal blood perfusion and no iodinated contrast, (B) normal perfusion and iodinated contrast infusion or (C) no blood perfusion and residual iodinated contrast. Changes in CT attenuation were analyzed from before, during and after ablation to evaluate whether contrast was trapped inside of the ablation zone. Visualization was compared between groups using post-ablation contrast-to-noise ratio (CNR). Attenuation gradients were calculated at the ablation boundary and background to quantitate ablation conspicuity. In Group A, attenuation decreased during ablation due to thermal expansion of tissue water and water vaporization. The ablation zone was difficult to visualize (CNR  =  1.57  ±  0.73, boundary gradient  =  0.7  ±  0.4 HU mm-1), leading to ablation diameter underestimation compared to gross pathology. Group B ablations saw attenuation increase, suggesting that iodine was trapped inside the ablation zone. However, because the normally perfused liver increased even more, Group B ablations were more visible than Group A (CNR  =  2.04  ±  0.84, boundary gradient  =  6.3  ±  1.1 HU mm-1) and allowed accurate estimation of the ablation zone dimensions compared to gross pathology. Substantial water vaporization led to substantial attenuation changes in Group C, though the ablation zone boundary was not highly visible (boundary gradient  =  3.9  ±  1.1 HU mm-1). Our results demonstrate that despite iodinated contrast being trapped in the ablation zone, ablation visibility was

  9. Lectin receptor kinase LecRK-b2 localizes to plasma membrane and ...

    African Journals Online (AJOL)



    Jul 20, 2009 ... medium (0.5× MS salt and 0.8% Agar at pH 5.8) in a petri dish. ... resuspended in sterile water and dropped onto SD medium- ... freezing and thawing between liquid nitrogen and room tempera- ... One millimolar luciferin was added to ... Each data point ... resulted in a significant increase in LUC activity.

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


    levels as well as 5α-Dihydrotestosterone ( DHT ) levels were diminished in xenografts from C4- 2B-shp52 cells compared to C4-2B-shEGFP cells. These...processed using MassLynx 4.1 software. Results showed that intracellular levels of both testosterone as well as DHT were greatly reduced in LN-p52 cells...the more active androgens, testosterone, and DHT , respectively. To further confirm that intracellular androgen syn thesis was acquired by C4 2B MDVR

  11. 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.

  12. Catheter ablation for atrial fibrillation after an unsuccessful surgical ablation and biological prosthetic mitral valve replacement: A pilot study

    Directory of Open Access Journals (Sweden)

    Sergey E. Mamchur


    Conclusion: Catheter ablation is an effective method for AF treatment following an ineffective surgical RF ablation procedure and biological prosthetic MV replacement. The use of bioprosthetic MVs allows for performing safe catheter ablation without subsequent prosthetic dysfunction.

  13. 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.

  14. 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.

  15. 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.

  16. Enhanced MgB2 Superconductivity Under High Pressure

    Institute of Scientific and Technical Information of China (English)

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


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

  17. 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. 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...... services to large Scandinavian corporations. We account for and analyse the process of building a mystery shopping procedure to get strategic insights from engineers delivering temporary consultancy services to these clients. After a successful trial period with three mystery shoppers the experiment (a...... 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....

  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. Model of the Sgr B2 radio source

    Energy Technology Data Exchange (ETDEWEB)

    Gosachinskii, I.V.; Khersonskii, V.K. (AN SSSR, Spetsial' naya Astrofizicheskaya Observatoriya)

    The dynamical model of the gas cloud around the radio source Sagittarius B2 is suggested. This model describes the kinematic features of the gas in this source: contraction of the core and rotation of the envelope. The stability of the cloud at the initial stage is supported by the turbulent motion of the gas, turbulence energy dissipates due to magnetic viscosity. This process is occurring more rapidly in the dense core and the core begins to collapse but the envelope remains stable. The parameters of the primary cloud and some parameters (mass, density and size) of the collapse are calculated. The conditions in the core at the moment of its fragmentation into masses of stellar order are established.

  1. Limits on refractive interstellar scattering toward Sagittarius B2

    Energy Technology Data Exchange (ETDEWEB)

    Gwinn, C.R.; Moran, J.M.; Reid, M.J.; Schneps, M.H.


    In this paper, an upper limit is placed on the spectral index of density fluctuations in the interstellar plasma by comparing apparent maser sizes, due to small-scale fluctuations, with wander in position of masers about constant-velocity paths, due to refraction by large-scale fluctuations. The scattered images of H/sub 2/O maser spots in Sgr B2(N) are about 300 microarcseconds in diameter (FWHM), while their deviation from constant-velocity motion is less than 18 microarcseconds. These two measurements constrain possible power-law spectra of the density fluctuations to indices less than or about the Kolmogorov value of 3.67; alternatively, the spectrum may have a long-wavelength cutoff at about 10 to the 13th cm. 27 references.

  2. 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%.

  3. 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.

  4. 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.

  5. 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...

  6. 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.

  7. Effects of HfB2 and HfN Additions on the Microstructures and Mechanical Properties of TiB2-Based Ceramic Tool Materials

    Directory of Open Access Journals (Sweden)

    Jing An


    Full Text Available The effects of HfB2 and HfN additions on the microstructures and mechanical properties of TiB2-based ceramic tool materials were investigated. The results showed that the HfB2 additive not only can inhibit the TiB2 grain growth but can also change the morphology of some TiB2 grains from bigger polygons to smaller polygons or longer ovals that are advantageous for forming a relatively fine microstructure, and that the HfN additive had a tendency toward agglomeration. The improvement of flexural strength and Vickers hardness of the TiB2-HfB2 ceramics was due to the relatively fine microstructure; the decrease of fracture toughness was ascribed to the formation of a weaker grain boundary strength due to the brittle rim phase and the poor wettability between HfB2 and Ni. The decrease of the flexural strength and Vickers hardness of the TiB2-HfN ceramics was due to the increase of defects such as TiB2 coarse grains and HfN agglomeration; the enhancement of fracture toughness was mainly attributed to the decrease of the pore number and the increase of the rim phase and TiB2 coarse grains. The toughening mechanisms of TiB2-HfB2 ceramics mainly included crack bridging and transgranular fracture, while the toughening mechanisms of TiB2-HfN ceramics mainly included crack deflection, crack bridging, transgranular fracture, and the core-rim structure.

  8. Possible role for cryoballoon ablation of right atrial appendage tachycardia when conventional ablation fails. (United States)

    Amasyali, Basri; Kilic, Ayhan


    Focal atrial tachycardia arising from the right atrial appendage usually responds well to radiofrequency ablation; however, successful ablation in this anatomic region can be challenging. Surgical excision of the right atrial appendage has sometimes been necessary to eliminate the tachycardia and prevent or reverse the resultant cardiomyopathy. We report the case of a 48-year-old man who had right atrial appendage tachycardia resistant to multiple attempts at ablation with use of conventional radiofrequency energy guided by means of a 3-dimensional mapping system. The condition led to cardiomyopathy in 3 months. The arrhythmia was successfully ablated with use of a 28-mm cryoballoon catheter that had originally been developed for catheter ablation of paroxysmal atrial fibrillation. To our knowledge, this is the first report of cryoballoon ablation without isolation of the right atrial appendage. It might also be an alternative to epicardial ablation or surgery when refractory atrial tachycardia originates from the right atrial appendage.

  9. 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.

  10. Attitudes Towards Catheter Ablation for Atrial Fibrillation

    DEFF Research Database (Denmark)

    Vadmann, Henrik; Pedersen, Susanne S; Nielsen, Jens Cosedis;


    BACKGROUND: Catheter ablation for atrial fibrillation (AF) is an important but expensive procedure that is the subject of some debate. Physicians´ attitudes towards catheter ablation may influence promotion and patient acceptance. This is the first study to examine the attitudes of Danish...

  11. Laser systems for ablative fractional resurfacing

    DEFF Research Database (Denmark)

    Paasch, Uwe; Haedersdal, Merete


    Ablative fractional resurfacing (AFR) creates microscopic vertical ablated channels that are surrounded by a thin layer of coagulated tissue, constituting the microscopic treatment zones (MTZs). AFR induces epidermal and dermal remodeling, which raises new possibilities for the treatment of a var...

  12. Therapy of HCC-radiofrequency ablation. (United States)

    Buscarini, L; Buscarini, E


    Radiofrequency interstitial hyperthermia has been used for percutaneous ablation of hepatocellular carcinoma, under ultrasound guidance in local anesthesia. Conventional needle electrodes require a mean number of 3 sessions to treat tumors of diameter hemotorax in one case; a fluid collection in the site of ablated tumor in one patient treated by combination of transcatheter arterial embolization and radiofrequency application.

  13. Effective temperatures of polymer laser ablation (United States)

    Furzikov, Nickolay P.


    Effective temperatures of laser ablation of certain polymers are extracted from experimental dependences of ablation depths on laser fluences. Dependence of these temperatures on laser pulse durations is established. Comparison with the known thermodestruction data shows that the effective temperature corresponds to transient thermodestruction proceeding by the statistically most probable way.

  14. VUV laser ablation of polymers. Photochemical aspect (United States)

    Castex, M. C.; Bityurin, N.; Olivero, C.; Muraviov, S.; Bronnikova, N.; Riedel, D.


    A photochemical theory of laser ablation owing to the direct chain scission process is considered in quite general form taking into account the modification of material. The formulas obtained can be used for estimating mechanisms of VUV laser ablation of polymers.

  15. High Heat Flux Block Ablator-in-Honeycomb Heat Shield Using Ablator/Aerogel-Filled Foam Project (United States)

    National Aeronautics and Space Administration — Ultramet and ARA Ablatives Laboratory previously developed and demonstrated advanced foam-reinforced carbon/phenolic ablators that offer substantially increased high...

  16. Tumor ablation with irreversible electroporation.

    Directory of Open Access Journals (Sweden)

    Bassim Al-Sakere

    Full Text Available We report the first successful use of irreversible electroporation for the minimally invasive treatment of aggressive cutaneous tumors implanted in mice. Irreversible electroporation is a newly developed non-thermal tissue ablation technique in which certain short duration electrical fields are used to permanently permeabilize the cell membrane, presumably through the formation of nanoscale defects in the cell membrane. Mathematical models of the electrical and thermal fields that develop during the application of the pulses were used to design an efficient treatment protocol with minimal heating of the tissue. Tumor regression was confirmed by histological studies which also revealed that it occurred as a direct result of irreversible cell membrane permeabilization. Parametric studies show that the successful outcome of the procedure is related to the applied electric field strength, the total pulse duration as well as the temporal mode of delivery of the pulses. Our best results were obtained using plate electrodes to deliver across the tumor 80 pulses of 100 micros at 0.3 Hz with an electrical field magnitude of 2500 V/cm. These conditions induced complete regression in 12 out of 13 treated tumors, (92%, in the absence of tissue heating. Irreversible electroporation is thus a new effective modality for non-thermal tumor ablation.

  17. Femtosecond ablation of ultrahard materials (United States)

    Dumitru, G.; Romano, V.; Weber, H. P.; Sentis, M.; Marine, W.

    Several ultrahard materials and coatings of definite interest for tribological applications were tested with respect to their response when irradiated with fs laser pulses. Results on cemented tungsten carbide and on titanium carbonitride are reported for the first time and compared with outcomes of investigations on diamond and titanium nitride. The experiments were carried out in air, in a regime of 5-8 J/cm2 fluences, using the beam of a commercial Ti:sapphire laser. The changes induced in the surface morphology were analysed with a Nomarski optical microscope, and with SEM and AFM techniques. From the experimental data and from the calculated incident energy density distributions, the damage and ablation threshold values were determined. As expected, the diamond showed the highest threshold, while the cemented tungsten carbide exhibited typical values for metallic surfaces. The ablation rates determined (under the above-mentioned experimental conditions) were in the range 0.1-0.2 μm per pulse for all the materials investigated.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  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. 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



  11. 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.

  12. 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.

  13. Analysis of infrared laser tissue ablation (United States)

    McKenzie, Gordon P.; Timmerman, Brenda H.; Bryanston-Cross, Peter J.


    The mechanisms involved in infrared laser tissue ablation are studied using a free electron laser (FELIX) in order to clarify whether the increased ablation efficiency reported in literature for certain infrared wavelengths is due to a wavelength effect or to the specific pulse structure of the lasers that are generally used in these studies. Investigations are presented of ablation of vitreous from pigs" eyes using several techniques including protein gel electrophoresis and ablation plume visualization. The ablation effects of three different infrared wavelengths are compared: 3 mm, which is currently in clinical surgical use, and the wavelengths associated with the amide I and amide II bands, i.e. 6.2 mm and 6.45mm, respectively. The results suggest a different ablation mechanism to be in operation for each studied wavelength, thus indicating that the generally reported increased ablation efficiency in the 6-6.5 micron range is due to the wavelength rather than the typical free electron laser pulse structure.

  14. 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.

  15. 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.

  16. 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.

  17. UV Laser Ablation of Electronically Conductive Polymers (United States)


    deionized water. The polymerization solution for polyaniline was prepared by mixing equal volumes of a solution that was 0.25 M in ammonium persulfate with a...rum2,0 vvcsL) TbeUV.layer ablation of thin polypyrrole and polyaniline films coated on an insulating substrate is described. UV laser ablation is used to...11liiii929. 6 1 2:- A ABSTRACT The UV laser ablation of thin polypyrrole and polyaniline films coated on an insulating substrate is described. UV laser

  18. Hydrodynamic modeling of ns-laser ablation

    Directory of Open Access Journals (Sweden)

    David Autrique


    Full Text Available Laser ablation is a versatile and widespread technique, applied in an increasing number of medical, industrial and analytical applications. A hydrodynamic multiphase model describing nanosecond-laser ablation (ns-LA is outlined. The model accounts for target heating and mass removal mechanisms as well as plume expansion and plasma formation. A copper target is placed in an ambient environment consisting of helium and irradiated by a nanosecond-laser pulse. The effect of variable laser settings on the ablation process is explored in 1-D numerical simulations.

  19. Diamond Ablators for Inertial Confinement Fusion

    Energy Technology Data Exchange (ETDEWEB)

    Biener, J; Mirkarimi, P B; Tringe, J W; Baker, S L; Wang, Y M; Kucheyev, S O; Teslich, N E; Wu, K J; Hamza, A V; Wild, C; Woerner, E; Koidl, P; Bruehne, K; Fecht, H


    Diamond has a unique combination of physical properties for the inertial confinement fusion ablator application, such as appropriate optical properties, high atomic density, high yield strength, and high thermal conductivity. Here, we present a feasible concept to fabricate diamond ablator shells. The fabrication of diamond capsules is a multi-step process, which involves diamond chemical vapor deposition on silicon mandrels followed by polishing, microfabrication of holes, and removing of the silicon mandrel by an etch process. We also discuss the pros and cons of coarse-grained optical quality and nanocrystalline chemical vapor deposition diamond films for the ablator application.

  20. Ablation response testing of aerospace power supplies (United States)

    Lutz, S. A.; Chan, C. C.


    An experimental program was performed to assess the aerothermal ablation response of aerospace power supplies. Full-scale General Purpose Heat Source (GPHS) test articles, Graphite Impact Shell (GIS) test articles, and Lightweight Radioisotope Heater Unit (LWRHU) test articles were all tested without nuclear fuel in simulated reentry environments at the NASA Ames Research Center. Stagnation heating, stagnation pressure, stagnation surface temperature, stagnation surface recession profile, and weight loss measurements were obtained for diffusion-limited and sublimation ablation conditions. The recession profile and weight loss measurements showed an effect of surface features on the stagnation face. The surface features altered the local heating which in turn affected the local ablation.

  1. Use of a circular mapping and ablation catheter for ablation of atypical right ventricular outflow tract arrhythmia. (United States)

    Katritsis, Demosthenes G; Giazitzoglou, Eleftherios; Paxinos, George


    A new technique for ablation of persistent ectopic activity with atypical electrocardiographic characteristics at the vicinity of the right ventricular outflow tract is described. A new circular mapping and ablation catheter initially designed for pulmonary vein ablation was used. Abolition of ectopic activity was achieved with minimal fluoroscopy and ablation times.

  2. 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

  3. Cryoballoon or Radiofrequency Ablation for Paroxysmal Atrial Fibrillation.


    Chun, KR; Bestehorn, K; Pocock, SJ; FIRE AND ICE Investigators; , COLLABORATORS; Kuck, KH; Metzner, A; Ouyang, F; Chun, J; Fürnkranz, A; Elvan, A.; Arentz, T.; Kühne, M.; Sticherling, C; Gellér, L


    BACKGROUND: Current guidelines recommend pulmonary-vein isolation by means of catheter ablation as treatment for drug-refractory paroxysmal atrial fibrillation. Radiofrequency ablation is the most common method, and cryoballoon ablation is the second most frequently used technology. METHODS: We conducted a multicenter, randomized trial to determine whether cryoballoon ablation was noninferior to radiofrequency ablation in symptomatic patients with drug-refractory paroxysmal atrial fibrillatio...

  4. Towards a sharp distinction between b2b and b2c? On consumer, commercial and general contract law after the consumer rights directive

    NARCIS (Netherlands)

    Hesselink, M.


    The proposed directive fits very well with a sharp distinction between b2c and b2b contracts and comprises several features that - especially as a combination - provide an optimal basis for a future European consumer (contract) code. Still, nothing in the directive renders further distinction

  5. 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...

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

    Lifescience Database Archive (English)


  7. 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...

  8. Nanosecond laser ablation of silver nanoparticle film (United States)

    Chung, Jaewon; Han, Sewoon; Lee, Daeho; Ahn, Sanghoon; Grigoropoulos, Costas P.; Moon, Jooho; Ko, Seung H.


    Nanosecond laser ablation of polyvinylpyrrolidone (PVP) protected silver nanoparticle (20 nm diameter) film is studied using a frequency doubled Nd:YAG nanosecond laser (532 nm wavelength, 6 ns full width half maximum pulse width). In the sintered silver nanoparticle film, absorbed light energy conducts well through the sintered porous structure, resulting in ablation craters of a porous dome shape or crown shape depending on the irradiation fluence due to the sudden vaporization of the PVP. In the unsintered silver nanoparticle film, the ablation crater with a clean edge profile is formed and many coalesced nanoparticles of 50 to 100 nm in size are observed inside the ablation crater. These results and an order of magnitude analysis indicate that the absorbed thermal energy is confined within the nanoparticles, causing melting of nanoparticles and their coalescence to larger agglomerates, which are removed following melting and subsequent partial vaporization.

  9. Laser ablation in analytical chemistry - A review

    Energy Technology Data Exchange (ETDEWEB)

    Russo, Richard E.; Mao, Xianglei; Liu, Haichen; Gonzalez, Jhanis; Mao, Samuel S.


    Laser ablation is becoming a dominant technology for direct solid sampling in analytical chemistry. Laser ablation refers to the process in which an intense burst of energy delivered by a short laser pulse is used to sample (remove a portion of) a material. The advantages of laser ablation chemical analysis include direct characterization of solids, no chemical procedures for dissolution, reduced risk of contamination or sample loss, analysis of very small samples not separable for solution analysis, and determination of spatial distributions of elemental composition. This review describes recent research to understand and utilize laser ablation for direct solid sampling, with emphasis on sample introduction to an inductively coupled plasma (ICP). Current research related to contemporary experimental systems, calibration and optimization, and fractionation is discussed, with a summary of applications in several areas.

  10. Nanoscale ablation through optically trapped microspheres (United States)

    Fardel, Romain; McLeod, Euan; Tsai, Yu-Cheng; Arnold, Craig B.


    The ability to directly create patterns with size scales below 100 nm is important for many applications where the production or repair of high resolution and density features is needed. Laser-based direct-write methods have the benefit of being able to quickly and easily modify and create structures on existing devices, but ablation can negatively impact the overall technique. In this paper we show that self-positioning of near-field objectives through the optical trap assisted nanopatterning (OTAN) method allows for ablation without harming the objective elements. Small microbeads are positioned in close proximity to a substrate where ablation is initiated. Upon ablation, these beads are temporarily displaced from the trap but rapidly return to the initial position. We analyze the range of fluence values for which this process occurs and find that there exists a critical threshold beyond which the beads are permanently ejected.

  11. Physical processes of laser tissue ablation (United States)

    Furzikov, Nickolay P.


    The revised ablation model applicable to homogeneous tissues is presented. It is based on the thermal mechanism and involves the instability of the laserinduced evaporation (thermodestruction) front the growth of the surface ripple structure the interference of the laser wave and of the surface wave arising by diffraction on the ripples Beer''s law violation the pulsed thermodestruction of the organic structural component the tissue water boiling and gas dynamic expansion of the resulting products into the surrounding medium which is followed by the shock wave formation. The UV and IR ablation schemes were implemented and compared to the corneal ablation experiments. The initial ablation pressure and temperature are given restored from the timeofflight measurements of the supersonic expansion of the product. 1.

  12. Laser ablation of a polysilane material (United States)

    Hansen, S. G.; Robitaille, T. E.


    The laser ablation properties of a (50%)-isopropyl methyl-(50%)-n-propyl methyl silane copolymer are examined. Both 193- and 248-nm-pulsed excimer laser radiation cleanly and completely remove this material in vacuum above certain energy thresholds (30 and 50 mJ/cm2, respectively). Under these conditions the ablation properties are quite similar to those reported for typical organic polymers. Below threshold, ablation is less efficient and becomes increasingly inefficient as irradiation continues due to spectral bleaching. In the presence of air, material removal is incomplete even for high-energy densities and long exposures. The ablation rate is shown to be independent of substrate material both above and below threshold.

  13. Ablative Ceramic Foam Based TPS Project (United States)

    National Aeronautics and Space Administration — A novel composite material ablative TPS for planetary vehicles that can survive a dual heating exposure is proposed. NextGen's TPS concept is a bi-layer functional...

  14. 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.

  15. 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.

  16. 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.

  17. 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...

  18. Principles of the radiative ablation modeling (United States)

    Saillard, Yves; Arnault, Philippe; Silvert, Virginie


    Indirectly driven inertial confinement fusion (ICF) rests on the setting up of a radiation temperature within a laser cavity and on the optimization of the capsule implosion ablated by this radiation. In both circumstances, the ablation of an optically thick medium is at work. The nonlinear radiation conduction equations that describe this phenomenon admit different kinds of solutions called generically Marshak waves. In this paper, a completely analytic model is proposed to describe the ablation in the subsonic regime relevant to ICF experiments. This model approximates the flow by a deflagrationlike structure where Hugoniot relations are used in the stationary part from the ablation front up to the isothermal sonic Chapman-Jouguet point and where the unstationary expansion from the sonic point up to the external boundary is assumed quasi-isothermal. It uses power law matter properties. It can also accommodate arbitrary boundary conditions provided the ablation wave stays very subsonic and the surface temperature does not vary too quickly. These requirements are often met in realistic situations. Interestingly, the ablated mass rate, the ablation pressure, and the absorbed radiative energy depend on the time history of the surface temperature, not only on the instantaneous temperature values. The results compare very well with self-similar solutions and with numerical simulations obtained by hydrodynamic code. This analytic model gives insight into the physical processes involved in the ablation and is helpful for optimization and sensitivity studies in many situations of interest: radiation temperature within a laser cavity, acceleration of finite size medium, and ICF capsule implosion, for instance.


    Directory of Open Access Journals (Sweden)

    Ch. Madh


    Full Text Available Adenoma sebaceum, pathognomonic of tuberous sclerosis, are tiny angiofibromas which commonly occur over central part of face. Recurrence after treatment is common and hence a need for inexpensive, safe and efficient treatment is required. Radiofrequency ablation is a safe and an economical procedure and has been known to cause less scarring with good aesthetic results compared to other ablative methods such as electrocautery.

  20. 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.

  1. Convergent Evolution of Head Crests in Two Domesticated Columbids Is Associated with Different Missense Mutations in EphB2. (United States)

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


    Head crests are important display structures in wild bird species and are also common in domesticated lineages. Many breeds of domestic rock pigeon (Columba livia) have crests of reversed occipital feathers, and this recessive trait is associated with a nonsynonymous coding mutation in the intracellular kinase domain of EphB2 (Ephrin receptor B2). The domestic ringneck dove (Streptopelia risoria) also has a recessive crested morph with reversed occipital feathers, and interspecific crosses between crested doves and pigeons produce crested offspring, suggesting a similar genetic basis for this trait in both species. We therefore investigated EphB2 as a candidate for the head crest phenotype of ringneck doves and identified a nonsynonymous coding mutation in the intracellular kinase domain that is significantly associated with the crested morph. This mutation is over 100 amino acid positions away from the crest mutation found in rock pigeons, yet both mutations are predicted to negatively affect the function of ATP-binding pocket. Furthermore, bacterial toxicity assays suggest that "crest" mutations in both species severely impact kinase activity. We conclude that head crests are associated with different mutations in the same functional domain of the same gene in two different columbid species, thereby representing striking evolutionary convergence in morphology and molecules. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail:

  2. Pressure-induced phase transition and electronic properties of MgB2C2 (United States)

    Zheng, Baobing


    Two thermodynamically stable new high-pressure phases of MgB2C2 with P-3m1 and I4 cm structure were uncovered through first principles crystal structure search based on unbiased evolutionary simulations. Compared with oC80-MgB2C2 and oP10-MgB2C2 phases, the theoretically predicted hP5-MgB2C2 and tI20-MgB2C2 phases show an intriguing three-dimensional (3D) sp3 B-C bonded network, instead of original 2D sp2 B-C layers, which has been confirmed with the analysis of their structures and partial densities of states. The phase transitions of oC80-MgB2C2 → oP10-MgB2C2, oP10-MgB2C2 → hP5-MgB2C2, and hP5-MgB2C2 → tI20-MgB2C2 occur at 4.6 GPa, 18.9 GPa, and 247.5 GPa, respectively, which have been determined according to the examination of enthalpy differences curves. Electronic band structure calculations suggest that the oC80-MgB2C2, oP10-MgB2C2 and hP5-MgB2C2 phases are indirect band gap semiconductor, while the tI20-MgB2C2 phase changes to direct band gap semiconductor.

  3. 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.

  4. 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

  5. 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...

  6. Submillimeter continuum observations of Sagittarius B2 at subarcsecond spatial resolution


    Qin, S. -L.; Schilke, P.; Rolffs, R.; Comito, C.; Lis, D. C.; Zhang, Q


    We report the first high spatial resolution submillimeter continuum observations of the Sagittarius B2 cloud complex using the Submillimeter Array (SMA). With the subarcsecond resolution provided by the SMA, the two massive star-forming clumps Sgr B2(N) and Sgr B2(M) are resolved into multiple compact sources. In total, twelve submillimeter cores are identified in the Sgr B2(M) region, while only two components are observed in the Sgr B2(N) clump. The gas mass and column density are estimated...

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. Percutaneous Microwave Ablation of Renal Angiomyolipomas

    Energy Technology Data Exchange (ETDEWEB)

    Cristescu, Mircea, E-mail: [University of Wisconsin, Department of Radiology (United States); Abel, E. Jason, E-mail: [University of Wisconsin, Department of Urology (United States); Wells, Shane, E-mail:; Ziemlewicz, Timothy J., E-mail: [University of Wisconsin, Department of Radiology (United States); Hedican, Sean P., E-mail: [University of Wisconsin, Department of Urology (United States); Lubner, Megan G., E-mail:; Hinshaw, J. Louis, E-mail:; Brace, Christopher L., E-mail:; Lee, Fred T., E-mail: [University of Wisconsin, Department of Radiology (United States)


    PurposeTo evaluate the safety and efficacy of US-guided percutaneous microwave (MW) ablation in the treatment of renal angiomyolipoma (AML).Materials and MethodsFrom January 2011 to April 2014, seven patients (5 females and 2 males; mean age 51.4) with 11 renal AMLs (9 sporadic type and 2 tuberous sclerosis associated) with a mean size of 3.4 ± 0.7 cm (range 2.4–4.9 cm) were treated with high-powered, gas-cooled percutaneous MW ablation under US guidance. Tumoral diameter, volume, and CT/MR enhancement were measured on pre-treatment, immediate post-ablation, and delayed post-ablation imaging. Clinical symptoms and creatinine were assessed on follow-up visits.ResultsAll ablations were technically successful and no major complications were encountered. Mean ablation parameters were ablation power of 65 W (range 60–70 W), using 456 mL of hydrodissection fluid per patient, over 4.7 min (range 3–8 min). Immediate post-ablation imaging demonstrated mean tumor diameter and volume decreases of 1.8 % (3.4–3.3 cm) and 1.7 % (27.5–26.3 cm{sup 3}), respectively. Delayed imaging follow-up obtained at a mean interval of 23.1 months (median 17.6; range 9–47) demonstrated mean tumor diameter and volume decreases of 29 % (3.4–2.4 cm) and 47 % (27.5–12.1 cm{sup 3}), respectively. Tumoral enhancement decreased on immediate post-procedure and delayed imaging by CT/MR parameters, indicating decreased tumor vascularity. No patients required additional intervention and no patients experienced spontaneous bleeding post-ablation.ConclusionOur early experience with high-powered, gas-cooled percutaneous MW ablation demonstrates it to be a safe and effective modality to devascularize and decrease the size of renal AMLs.

  12. Dust ablation in Pluto's atmosphere (United States)

    Horanyi, Mihaly; Poppe, Andrew; Sternovsky, Zoltan


    Based on measurements by dust detectors onboard the Pioneer 10/11 and New Horizons spacecraft the total production rate of dust particles born in the Edgeworth Kuiper Belt (EKB) has been be estimated to be on the order of 5 ṡ 103 kg/s in the approximate size range of 1 - 10 μm. Dust particles are produced by collisions between EKB objects and their bombardment by both interplanetary and interstellar dust particles. Dust particles of EKB origin, in general, migrate towards the Sun due to Poynting-Robertson drag but their distributions are further sculpted by mean-motion resonances as they first approach the orbit of Neptune and later the other planets, as well as mutual collisions. Subsequently, Jupiter will eject the vast majority of them before they reach the inner solar system. The expected mass influx into Pluto atmosphere is on the order of 200 kg/day, and the arrival speed of the incoming particles is on the order of 3 - 4 km/s. We have followed the ablation history as function of speed and size of dust particles in Pluto's atmosphere, and found that volatile rich particles can fully sublimate due to drag heating and deposit their mass in narrow layers. This deposition might promote the formation of the haze layers observed by the New Horizons spacecraft. This talk will explore the constraints on the composition of the dust particles by comparing the altitude of the deposition layers to the observed haze layers.

  13. Fractional ablative erbium YAG laser

    DEFF Research Database (Denmark)

    Taudorf, Elisabeth H; Haak, Christina S; Erlendsson, Andrés M


    BACKGROUND AND OBJECTIVES: Treatment of a variety of skin disorders with ablative fractional lasers (AFXL) is driving the development of portable AFXLs. This study measures micropore dimensions produced by a small 2,940 nm AFXL using a variety of stacked pulses, and determines a model correlating...... laser parameters with tissue effects. MATERIALS AND METHODS: Ex vivo pig skin was exposed to a miniaturized 2,940 nm AFXL, spot size 225 µm, density 5%, power levels 1.15-2.22 W, pulse durations 50-225 microseconds, pulse repetition rates 100-500 Hz, and 2, 20, or 50 stacked pulses, resulting in pulse...... 190 to 347 µm. CONCLUSIONS: Pulse stacking with a small, low power 2,940 nm AFXL created reproducible shallow to deep micropores, and influenced micropore configuration. Mathematical modeling established relations between laser settings and micropore dimensions, which assists in choosing laser...

  14. The Confluence of Stereotactic Ablative Radiotherapy and Tumor Immunology

    Directory of Open Access Journals (Sweden)

    Steven Eric Finkelstein


    Full Text Available Stereotactic radiation approaches are gaining more popularity for the treatment of intracranial as well as extracranial tumors in organs such as the liver and lung. Technology, rather than biology, is driving the rapid adoption of stereotactic body radiation therapy (SBRT, also known as stereotactic ablative radiotherapy (SABR, in the clinic due to advances in precise positioning and targeting. Dramatic improvements in tumor control have been demonstrated; however, our knowledge of normal tissue biology response mechanisms to large fraction sizes is lacking. Herein, we will discuss how SABR can induce cellular expression of MHC I, adhesion molecules, costimulatory molecules, heat shock proteins, inflammatory mediators, immunomodulatory cytokines, and death receptors to enhance antitumor immune responses.

  15. 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.

  16. 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



  17. 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.

  18. Femtosecond laser ablation of silicon in air and vacuum

    Institute of Scientific and Technical Information of China (English)

    Zehua Wu; Nan Zhang; Mingwei Wang; Xiaonong Zhu


    Femtosecond (fs) pulse laser ablation of silicon targets in air and in vacuum is investigated using a time-resolved shadowgraphic method. The observed dynamic process of the fs laser ablation of silicon in air is significantly different from that in vacuum. Similar to the ablation of metallic targets, while the shock wave front and a series of nearly concentric and semicircular stripes, as well as the contact front, are clearly identifiable in the process of ablation under 1 x 105 Pa, these phenomena are no longer observed when the ablation takes place in vacuum. Although the ambient air around the target strongly affects the evolution of the ablation plume, the three rounds of material ejection clearly observed in the shadowgraphs of fs laser ablation in standard air can also be distinguished in the process of ablation in vacuum. It is proven that the three rounds of material ejection are caused by different ablation mechanisms.%@@ Femtosecond(fs)pulse laser ablation of silicon targets in air and in vacuum is investigated using a timeresolved shadowgraphic method.The observed dynamic process of the fs laser ablation of silicon in air is significantly different from that in vacuum.Similar to the ablation of metallic targets,while the shock wave front and a series of nearly concentric and semicircular stripes,as well as the contact front,are clearly identifiable in the process of ablation under 1 x 105 Pa,these phenomena are no longer observed when the ablation takes place in vacuum.Although the ambient air around the target strongly affects the evolution of the ablation plume,the three rounds of material ejection clearly observed in the shadowgraphs of fs laser ablation in standard air can also be distinguished in the process of ablation in vacuum.It is proven that the three rounds of material ejection are caused by different ablation mechanisms.

  19. Laser Spectroscopic Study of CaH in the B^2σ^+ and D^2σ^+ States (United States)

    Watanabe, Kyohei; Uchida, Kanako; Kobayashi, Kaori; Matsushima, Fusakazu; Moriwaki, Yoshiki


    Calcium hydride is one of the abundant molecules in the stellar environment, and is considered as a probe of stellar analysis. Ab initio calculations have shown that the electronic excited states of CaH have complex potential curves. It is suggested that the B^2σ^+ state has an interesting double minimum potential due to the avoided crossing. Such a potential leads to drastic change of the rotational constants when the vibrational energy level goes across the potential barrier. Spectroscopic studies on CaH began in the 1920's, and many studies have been carried out since then. Bell et al. extensively assigned the D^2σ^+-X^2σ^+ bands in the UV region. Bernath's group has observed transitions in the IR and visible regions and identified their upper states as the A^2σ^+, B^2σ^+ and E^2σ^+ states. We have carried out a laser induced fluorescence (LIF) study in the UV region between 360 and 430 nm. We have produced CaH by using laser ablation of a calcium target in a hydrogen gas environment, then molecules have been excited by a second harmonic pulse of dye laser and the fluorescence from molecules have been detected through a monochromator. Detection of the D^2σ^+-X^2σ^+ bands already identified by Bell et al. indicates the production of CaH. In addition, many other bands have been also found and a few bands have been assigned by using the combination differences, the lower state of these bands have been confirmed to the vibrational ground state of X^2σ^+ state. We have tentatively assigned these bands as the B^2σ^+ -X^2σ^+ transition. We will discuss the assignment of these bands, together with the rotational constants comparing with those calculated from the ab initio potential. B. Barbuy, R. P. Schiavon, J. Gregorio-Hetem, P. D. Singh C. Batalha , Astron. Astrophys. Sippl. Ser. 101, 409 (1993). P. F. Weck and P. C .Stabcil, J. Chem. Phys. {118}, 9997 (2003). R. S. Mulliken, Phys. Rev. {25}, 509 (1925). G. D. Bell, M, Herman, J. W. C. Johns, and E. R

  20. Ablation enhancement of silicon by ultrashort double-pulse laser ablation

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Xin; Shin, Yung C. [Center for Laser-Based Manufacturing, School of Mechanical Engineering, Purdue University, West Lafayette, Indiana 47907 (United States)


    In this study, the ultrashort double-pulse ablation of silicon is investigated. An atomistic simulation model is developed to analyze the underlying physics. It is revealed that the double-pulse ablation could significantly increase the ablation rate of silicon, compared with the single pulse ablation with the same total pulse energy, which is totally different from the case of metals. In the long pulse delay range (over 1 ps), the enhancement is caused by the metallic transition of melted silicon with the corresponding absorption efficiency. At ultrashort pulse delay (below 1 ps), the enhancement is due to the electron excitation by the first pulse. The enhancement only occurs at low and moderate laser fluence. The ablation is suppressed at high fluence due to the strong plasma shielding effect.

  1. Photoacoustic characterization of radiofrequency ablation lesions (United States)

    Bouchard, Richard; Dana, Nicholas; Di Biase, Luigi; Natale, Andrea; Emelianov, Stanislav


    Radiofrequency ablation (RFA) procedures are used to destroy abnormal electrical pathways in the heart that can cause cardiac arrhythmias. Current methods relying on fluoroscopy, echocardiography and electrical conduction mapping are unable to accurately assess ablation lesion size. In an effort to better visualize RFA lesions, photoacoustic (PA) and ultrasonic (US) imaging were utilized to obtain co-registered images of ablated porcine cardiac tissue. The left ventricular free wall of fresh (i.e., never frozen) porcine hearts was harvested within 24 hours of the animals' sacrifice. A THERMOCOOLR Ablation System (Biosense Webster, Inc.) operating at 40 W for 30-60 s was used to induce lesions through the endocardial and epicardial walls of the cardiac samples. Following lesion creation, the ablated tissue samples were placed in 25 °C saline to allow for multi-wavelength PA imaging. Samples were imaged with a VevoR 2100 ultrasound system (VisualSonics, Inc.) using a modified 20-MHz array that could provide laser irradiation to the sample from a pulsed tunable laser (Newport Corp.) to allow for co-registered photoacoustic-ultrasound (PAUS) imaging. PA imaging was conducted from 750-1064 nm, with a surface fluence of approximately 15 mJ/cm2 maintained during imaging. In this preliminary study with PA imaging, the ablated region could be well visualized on the surface of the sample, with contrasts of 6-10 dB achieved at 750 nm. Although imaging penetration depth is a concern, PA imaging shows promise in being able to reliably visualize RF ablation lesions.

  2. Left Atrial Ablation for Atrial Fibrillation (United States)

    Sternik, Leonid; Schaff, Hartzel V.; Luria, David; Glikson, Michael; Kogan, Alexander; Malachy, Ateret; First, Maya; Raanani, Ehud


    The maze procedure is the gold standard for the ablation of atrial fibrillation, and the “box lesion” around the pulmonary veins is the most important part of this procedure. We have created this lesion with a bipolar radiofrequency ablator, abandoning the usual use of this device (to achieve bilateral epicardial isolation of the pulmonary veins). From March 2004 through the end of May 2010, we performed surgical ablation of atrial fibrillation in 240 patients. Of this number, 205 underwent operation by a hybrid maze technique and the remaining 35 (our study cohort) underwent the creation of a box lesion around the pulmonary veins by means of a bipolar radiofrequency device. Ablation lines were created by connecting the left atriotomy to the amputated left atrial appendage, with 2 ablation lines made with a bipolar radiofrequency device above and below the pulmonary veins. Lesions were made along the transverse and oblique sinuses by epicardial and endocardial application of a bipolar device. The left atrial isthmus was ablated by bipolar radiofrequency and cryoprobe. No complications were associated with the box lesion: 90% and 89% of patients were in sinus rhythm at 3 and 6 months of follow-up, respectively. By creating a box lesion around the pulmonary veins, we expect to improve transmurality by means of epicardial and endocardial ablation of 1 rather than 2 layers of atrial wall, as in epicardial pulmonary vein isolation. Isolation of the entire posterior wall of the left atrium is better electrophysiologically and renders dissection around the pulmonary veins unnecessary. PMID:21494518

  3. Mechanism of Spatiotemporal Distribution of Laser Ablated Materials

    Institute of Scientific and Technical Information of China (English)

    XU Rong-Qing; CUI Yi-Ping; LU Jian; NI Xiao-Wu


    Interaction between subsequent laser and ablated materials in laser processing changes the laser spatiotemporal distribution and has influences on the efficiency and quality of laser processing. The theoretical and experimental researches on transportation behayiour of ablated materials are provided. It is shown that the velocity distribution of ablated materials is determined by ablation mechanism. The transportation behaviour of ablated materials is controlled by diffusion mechanism and light field force during laser pulse duration while it is only determined by diffusion mechanism when the laser pulse terminates. In addition, the spatiotemporal distribution of ablated materials is presented.

  4. Laser ablation of hepatocellular carcinoma-A review

    Institute of Scientific and Technical Information of China (English)


    A wide range of local thermal ablative therapies have been developed in the treatment of non resectable hepatocellular carcinoma (HCC) in the last decade. Laser ablation (LA) and radiofrequency ablation (RFA) are the two most widely used of these. This article provides an up to date overview of the role of laser ablation in the local treatment of HCC. General principles, technique, image guidance and patient selection are discussed. A review of published data on treatment efficacy, long term outcome and complication rates of laser ablation is included and comparison with RFA made. The role of laser ablation in combination with transcatheter arterial chemoembolisation is also discussed.

  5. 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.

  6. 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.

  7. Properties of ZrB2 Thin Films Grown by E-Beam Evaporation (United States)

    Lad, Robert; Stewart, David; Sell, Julia; Bernhardt, George; Frankel, David; University of Maine Team


    Zirconium diboride (ZrB2) is a candidate material for many high temperature applications because it has a high melting point, high hardness, thermal shock resistance, and metallic conductivity. However, very little work has been reported concerning growth of ZrB2 thin films and high temperature oxidation behavior. In this study, ZrB2 films with nominal thickness of 200 nm have been deposited using electron-beam evaporation of either ZrB2 pellets or elemental B and Zr sources. The ZrB2 source yields a film that has a 1:1 Zr:B average composition as measured by X-ray photoelectron spectroscopy, consisting of ZrB2 precipitates within an amorphous Zr matrix as determined by X-ray diffraction. Use of elemental B and Zr sources allows precise control of film growth over a range of stoichiometries and yields ZrB2 films with much lower oxygen contamination. After annealing ZrB2 films to 1200°C in air, oxidation leads to a loss of B and formation of a textured monoclinic ZrO2 phase. Several strategies, including deposition of a thin Al2O3 capping layer over the ZrB2 film are being pursued in an attempt to stabilize the electrically conductive ZrB2 phase at high temperature, where it can be used for high temperature electronic devices in harsh environments. Supported by NSF grant # 1309983.

  8. 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



  9. 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。

  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. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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。

  17. Influence of TiB2 Addition on the Precipitation Kinetics in Al-7Si-0.3Mg In Situ TiB2 Composites (United States)

    Nandam, S. H.; Murty, B. S.; Sankaran, S.


    Precipitation behavior of the Al-7Si-0.3Mg/TiB2 in situ composites was investigated using differential scanning calorimetry and transmission electron microscopy, and it was found that Si precipitation is accelerated with increase in TiB2 content. Non-isothermal kinetic analysis clearly showed a decrease in the precipitation kinetics of the overaged metastable precipitates in the Mg2Si precipitation sequence.

  18. 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.

  19. Anorexia and Impaired Glucose Metabolism in Mice With Hypothalamic Ablation of Glut4 Neurons (United States)

    Ren, Hongxia; Lu, Taylor Y.; McGraw, Timothy E.


    The central nervous system (CNS) uses glucose independent of insulin. Nonetheless, insulin receptors and insulin-responsive glucose transporters (Glut4) often colocalize in neurons (Glut4 neurons) in anatomically and functionally distinct areas of the CNS. The apparent heterogeneity of Glut4 neurons has thus far thwarted attempts to understand their function. To answer this question, we used Cre-dependent, diphtheria toxin–mediated cell ablation to selectively remove basal hypothalamic Glut4 neurons and investigate the resulting phenotypes. After Glut4 neuron ablation, mice demonstrate altered hormone and nutrient signaling in the CNS. Accordingly, they exhibit negative energy balance phenotype characterized by reduced food intake and increased energy expenditure, without locomotor deficits or gross neuronal abnormalities. Glut4 neuron ablation affects orexigenic melanin-concentrating hormone neurons but has limited effect on neuropeptide Y/agouti-related protein and proopiomelanocortin neurons. The food intake phenotype can be partially normalized by GABA administration, suggesting that it arises from defective GABAergic transmission. Glut4 neuron–ablated mice show peripheral metabolic defects, including fasting hyperglycemia and glucose intolerance, decreased insulin levels, and elevated hepatic gluconeogenic genes. We conclude that Glut4 neurons integrate hormonal and nutritional cues and mediate CNS actions of insulin on energy balance and peripheral metabolism. PMID:25187366

  20. Anorexia and impaired glucose metabolism in mice with hypothalamic ablation of Glut4 neurons. (United States)

    Ren, Hongxia; Lu, Taylor Y; McGraw, Timothy E; Accili, Domenico


    The central nervous system (CNS) uses glucose independent of insulin. Nonetheless, insulin receptors and insulin-responsive glucose transporters (Glut4) often colocalize in neurons (Glut4 neurons) in anatomically and functionally distinct areas of the CNS. The apparent heterogeneity of Glut4 neurons has thus far thwarted attempts to understand their function. To answer this question, we used Cre-dependent, diphtheria toxin-mediated cell ablation to selectively remove basal hypothalamic Glut4 neurons and investigate the resulting phenotypes. After Glut4 neuron ablation, mice demonstrate altered hormone and nutrient signaling in the CNS. Accordingly, they exhibit negative energy balance phenotype characterized by reduced food intake and increased energy expenditure, without locomotor deficits or gross neuronal abnormalities. Glut4 neuron ablation affects orexigenic melanin-concentrating hormone neurons but has limited effect on neuropeptide Y/agouti-related protein and proopiomelanocortin neurons. The food intake phenotype can be partially normalized by GABA administration, suggesting that it arises from defective GABAergic transmission. Glut4 neuron-ablated mice show peripheral metabolic defects, including fasting hyperglycemia and glucose intolerance, decreased insulin levels, and elevated hepatic gluconeogenic genes. We conclude that Glut4 neurons integrate hormonal and nutritional cues and mediate CNS actions of insulin on energy balance and peripheral metabolism.

  1. 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

  2. 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



  3. 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.

  4. 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).

  5. 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。

  6. 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



  7. 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.

  8. Imaging in percutaneous ablation for atrial fibrillation

    Energy Technology Data Exchange (ETDEWEB)

    Maksimovic, Ruzica [Erasmus Medical Center, Department of Radiology, GD Rotterdam (Netherlands); Institute for Cardiovascular Diseases of the University Medical Center, Belgrade (Czechoslovakia); Dill, Thorsten [Kerckhoff-Heart Center, Department of Cardiology, Bad Nauheim (Germany); Ristic, Arsen D.; Seferovic, Petar M. [Institute for Cardiovascular Diseases of the University Medical Center, Belgrade (Czechoslovakia)


    Percutaneous ablation for electrical disconnection of the arrhythmogenic foci using various forms of energy has become a well-established technique for treating atrial fibrillation (AF). Success rate in preventing recurrence of AF episodes is high although associated with a significant incidence of pulmonary vein (PV) stenosis and other rare complications. Clinical workup of AF patients includes imaging before and after ablative treatment using different noninvasive and invasive techniques such as conventional angiography, transoesophageal and intracardiac echocardiography, computed tomography (CT) and magnetic resonance imaging (MRI), which offer different information with variable diagnostic accuracy. Evaluation before percutaneous ablation involves assessment of PVs (PV pattern, branching pattern, orientation and ostial size) to facilitate position and size of catheters and reduce procedure time as well as examining the left atrium (presence of thrombi, dimensions and volumes). Imaging after the percutaneous ablation is important for assessment of overall success of the procedure and revealing potential complications. Therefore, imaging methods enable depiction of PVs and the anatomy of surrounding structures essential for preprocedural management and early detection of PV stenosis and other ablation-related procedures, as well as long-term follow-up of these patients. (orig.)

  9. Percutaneous tumor ablation in medical radiology

    Energy Technology Data Exchange (ETDEWEB)

    Vogl, T.J.; Mack, M.G. [University Hospital Frankfurt Univ. (Germany). Inst. for Diagnostic and Interventional Radiology; Helmberger, T.K. [Klinikum Bogenhausen, Academic Teaching Hospital of the Technical Univ. Munich (Germany). Dept. for Diagnostic and Interventional Radiology and Nuclear Medicine; Reiser, M.F. (eds.) [University Hospitals - Grosshadern and Innenstadt Munich Univ. (Germany). Dept. of Clinical Radiology


    Thermal ablation has become an integral part of oncology, especially in the field of interventional oncology. This very comprehensive book encompasses the different technologies employed in thermal ablation, its indications and the results achieved in various clinical conditions. The first part of the book clearly explains the basics of thermal ablative techniques such as laser-induced thermotherapy, radiofrequency ablation, microwave ablation, cryotherapy, and localized tumor therapy. The latest developments in the application of minimally invasive therapies in localized neoplastic disease are demonstrated. In the main part of the book, techniques of guiding the applicators to the target structures by use of different imaging tools such as ultrasound, computed tomography and magnetic resonance imaging are discussed. The results are presented for a variety of clinical indications, including liver and lung tumors and metastases and some rather rare conditions involving the kidney, the head and neck, the prostate, and soft tissue structures. A large number of acknowledged experts have contributed to the book, which benefits from a lucid structure and excellent images. (orig.)

  10. Fundamental studies of pulsed laser ablation

    CERN Document Server

    Claeyssens, F


    dopant) have resulted in a coherent view of the resulting plume, which exhibits a multi-component structure correlated with different regimes of ablation, which are attributed to ejection from ZnO and ablation from a Zn melt. OES measurements show that the emitting Zn component within the plume accelerates during expansion in vacuum - an observation attributable to the presence of hot, fast electrons in the plume. The same acceleration behaviour is observed in the case of Al atomic emissions resulting from ablation of an Al target in vacuum. Deposition conditions, substrate temperature and background gas pressure were all varied in a quest for optimally aligned, high quality ZnO thin films. Initial ab initio calculations were performed also, to aid in understanding the stability of these c-axis aligned films. The pulsed ultraviolet (lambda = 193, 248 nm) laser ablation of graphite, polycrystalline diamond and ZnO targets has been investigated. Characteristics of the resulting plumes of ablated material have b...

  11. 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 ...

  12. 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.

  13. 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.

  14. 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。

  15. 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.

  16. 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.

  17. 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...

  18. 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).

  19. 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...

  20. Alcohol septal ablation in patients with hypertrophic obstructive cardiomyopathy

    DEFF Research Database (Denmark)

    Jensen, Morten K; Prinz, Christian; Horstkotte, Dieter;


    The infarction induced by alcohol septal ablation (ASA) may predispose to arrhythmia and sudden cardiac death (SCD).......The infarction induced by alcohol septal ablation (ASA) may predispose to arrhythmia and sudden cardiac death (SCD)....