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Sample records for b4 receptor blt1

  1. The leukotriene B4 receptors BLT1 and BLT2 form an antagonistic sensitizing system in peripheral sensory neurons.

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    Zinn, Sebastian; Sisignano, Marco; Kern, Katharina; Pierre, Sandra; Tunaru, Sorin; Jordan, Holger; Suo, Jing; Treutlein, Elsa-Marie; Angioni, Carlo; Ferreiros, Nerea; Leffler, Andreas; DeBruin, Natasja; Offermanns, Stefan; Geisslinger, Gerd; Scholich, Klaus

    2017-04-14

    Sensitization of the heat-activated ion channel transient receptor potential vanilloid 1 (TRPV1) through lipids is a fundamental mechanism during inflammation-induced peripheral sensitization. Leukotriene B4 is a proinflammatory lipid mediator whose role in peripheral nociceptive sensitization is not well understood to date. Two major G-protein-coupled receptors for leukotriene B4 have been identified: the high-affinity receptor BLT1 and the low-affinity receptor BLT2. Transcriptional screening for the expression G-protein-coupled receptors in murine dorsal root ganglia showed that both receptors were among the highest expressed in dorsal root ganglia. Calcium imaging revealed a sensitization of TRPV1-mediated calcium increases in a relative narrow concentration range for leukotriene B4 (100-200 nm). Selective antagonists and neurons from knock-out mice demonstrated a BLT1-dependent sensitization of TRPV1-mediated calcium increases. Accordingly, leukotriene B4-induced thermal hyperalgesia was mediated through BLT1 and TRPV1 as shown using the respective knock-out mice. Importantly, higher leukotriene B4 concentrations (>0.5 μm) and BLT2 agonists abolished sensitization of the TRPV1-mediated calcium increases. Also, BLT2 activation inhibited protein kinase C- and protein kinase A-mediated sensitization processes through the phosphatase calcineurin. Consequently, a selective BLT2-receptor agonist increased thermal and mechanical withdrawal thresholds during zymosan-induced inflammation. In accordance with these data, immunohistochemical analysis showed that both leukotriene B4 receptors were expressed in peripheral sensory neurons. Thus, the data show that the two leukotriene B4 receptors have opposing roles in the sensitization of peripheral sensory neurons forming a self-restricting system. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

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

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

    2010-04-09

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

  3. Biochemical and immunological characterization of a novel monoclonal antibody against mouse leukotriene B4 receptor 1

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    Sasaki, Fumiyuki; Koga, Tomoaki; Saeki, Kazuko; Okuno, Toshiaki; Kazuno, Saiko; Fujimura, Tsutomu; Ohkawa, Yasuyuki

    2017-01-01

    Leukotriene B4 (LTB4) receptor 1 (BLT1) is a G protein-coupled receptor expressed in various leukocyte subsets; however, the precise expression of mouse BLT1 (mBLT1) has not been reported because a mBLT1 monoclonal antibody (mAb) has not been available. In this study, we present the successful establishment of a hybridoma cell line (clone 7A8) that produces a high-affinity mAb for mBLT1 by direct immunization of BLT1-deficient mice with mBLT1-overexpressing cells. The specificity of clone 7A8 was confirmed using mBLT1-overexpressing cells and mouse peripheral blood leukocytes that endogenously express BLT1. Clone 7A8 did not cross-react with human BLT1 or other G protein-coupled receptors, including human chemokine (C-X-C motif) receptor 4. The 7A8 mAb binds to the second extracellular loop of mBLT1 and did not affect LTB4 binding or intracellular calcium mobilization by LTB4. The 7A8 mAb positively stained Gr-1-positive granulocytes, CD11b-positive granulocytes/monocytes, F4/80-positive monocytes, CCR2-high and CCR2-low monocyte subsets in the peripheral blood and a CD4-positive T cell subset, Th1 cells differentiated in vitro from naïve CD4-positive T cells. This mAb was able to detect Gr-1-positive granulocytes and monocytes in the spleens of naïve mice by immunohistochemistry. Finally, intraperitoneal administration of 7A8 mAb depleted granulocytes and monocytes in the peripheral blood. We have therefore succeeded in generating a high-affinity anti-mBLT1 mAb that is useful for analyzing mBLT1 expression in vitro and in vivo. PMID:28922396

  4. Biochemical and immunological characterization of a novel monoclonal antibody against mouse leukotriene B4 receptor 1.

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    Fumiyuki Sasaki

    Full Text Available Leukotriene B4 (LTB4 receptor 1 (BLT1 is a G protein-coupled receptor expressed in various leukocyte subsets; however, the precise expression of mouse BLT1 (mBLT1 has not been reported because a mBLT1 monoclonal antibody (mAb has not been available. In this study, we present the successful establishment of a hybridoma cell line (clone 7A8 that produces a high-affinity mAb for mBLT1 by direct immunization of BLT1-deficient mice with mBLT1-overexpressing cells. The specificity of clone 7A8 was confirmed using mBLT1-overexpressing cells and mouse peripheral blood leukocytes that endogenously express BLT1. Clone 7A8 did not cross-react with human BLT1 or other G protein-coupled receptors, including human chemokine (C-X-C motif receptor 4. The 7A8 mAb binds to the second extracellular loop of mBLT1 and did not affect LTB4 binding or intracellular calcium mobilization by LTB4. The 7A8 mAb positively stained Gr-1-positive granulocytes, CD11b-positive granulocytes/monocytes, F4/80-positive monocytes, CCR2-high and CCR2-low monocyte subsets in the peripheral blood and a CD4-positive T cell subset, Th1 cells differentiated in vitro from naïve CD4-positive T cells. This mAb was able to detect Gr-1-positive granulocytes and monocytes in the spleens of naïve mice by immunohistochemistry. Finally, intraperitoneal administration of 7A8 mAb depleted granulocytes and monocytes in the peripheral blood. We have therefore succeeded in generating a high-affinity anti-mBLT1 mAb that is useful for analyzing mBLT1 expression in vitro and in vivo.

  5. Inhibited aortic aneurysm formation in BLT1-deficient mice.

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    Ahluwalia, Neil; Lin, Alexander Y; Tager, Andrew M; Pruitt, Ivy E; Anderson, Thomas J T; Kristo, Fjoralba; Shen, Dongxiao; Cruz, Anna R; Aikawa, Masanori; Luster, Andrew D; Gerszten, Robert E

    2007-07-01

    Leukotriene B(4) is a proinflammatory lipid mediator generated by the enzymes 5-lipoxygenase and leukotriene A(4) hydrolase. Leukotriene B(4) signals primarily through its high-affinity G protein-coupled receptor, BLT1, which is highly expressed on specific leukocyte subsets. Recent genetic studies in humans as well as knockout studies in mice have implicated the leukotriene synthesis pathway in several vascular pathologies. In this study, we tested the hypothesis that BLT1 is necessary for abdominal aortic aneurysm (AAA) formation, a major complication of atherosclerotic vascular disease. Chow-fed Apoe(-/-) and Apoe(-/-)/Blt1(-/-) mice were treated with a 4-wk infusion of angiotensin II (1000 ng/min/kg) beginning at 20 wk of age, in a well-established murine AAA model. We found a reduced incidence of AAA formation as well as concordant reductions in the maximum suprarenal/infrarenal diameter and total suprarenal/infrarenal area in the angiotensin II-treated Apoe(-/-)/Blt1(-/-) mice as compared with the Apoe(-/-) controls. Diminished AAA formation in BLT1-deficient mice was associated with significant reductions in mononuclear cell chemoattractants and leukocyte accumulation in the vessel wall, as well as striking reductions in the production of matrix metalloproteinases-2 and -9. Thus, we have shown that BLT1 contributes to the frequency and size of abdominal aortic aneurysms in mice and that BLT1 deletion in turn inhibits proinflammatory circuits and enzymes that modulate vessel wall integrity. These findings extend the role of BLT1 to a critical complication of vascular disease and underscore its potential as a target for intervention in modulating multiple pathologies related to atherosclerosis.

  6. The leukotriene B4-leukotriene B4 receptor axis promotes cisplatin-induced acute kidney injury by modulating neutrophil recruitment.

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    Deng, Bo; Lin, Yuli; Ma, Shuai; Zheng, Yin; Yang, Xuguang; Li, Bingji; Yu, Wenyan; Xu, Qingqing; Liu, Tingyan; Hao, Chuanming; He, Rui; Ding, Feng

    2017-07-01

    Cisplatin is an effective chemotherapeutic agent and widely used in treatment of various solid organ malignancies, including head and neck, ovarian, and testicular cancers. However, the induction of acute kidney injury (AKI) is one of its main side effects. Leukotriene B 4 receptor 1 (BLT1) mediates the majority of physiological effects of leukotriene B 4 (LTB 4 ), a potent lipid chemoattractant generated at inflammation sites, but the role of the LTB 4 -BLT1 axis in cisplatin-induced AKI remains unknown. Here we found upregulated LTB 4 synthesis and BLT1 expression in the kidney after cisplatin administration. Cisplatin was found to directly upregulate gene expression of leukotriene A 4 hydrolase and stimulate LTB 4 production in renal tubular epithelial cells. Reduced kidney structural/functional damage, inflammation, and apoptosis were observed in BLT1 -/- mice, as well as in wild-type mice treated with the LTA4H inhibitor SC-57461A and the BLT1 antagonist U-75302. Neutrophils were likely the target of this pathway, as BLT1 absence induced a significant decrease in infiltrating neutrophils in the kidney. Adoptive transfer of neutrophils from wild-type mice restored kidney injury in BLT1 -/- mice following cisplatin challenge. Thus, the LTB 4 -BLT1 axis contributes to cisplatin-induced AKI by mediating kidney recruitment of neutrophils, which induce inflammation and apoptosis in the kidney. Hence, the LTB 4 -BLT1 axis could be a potential therapeutic target in cisplatin-induced AKI. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  7. The Role of Leukotriene B4 in Allergic Diseases

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    Hiroshi Ohnishi

    2008-01-01

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

  8. Cigarette smoke-induced lung inflammation in COPD mediated via LTB4/BLT1/SOCS1 pathway

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    Dong R

    2015-12-01

    Full Text Available Ran Dong,1,* Liang Xie,1,* Kaishun Zhao,2,* Qiurui Zhang,1 Min Zhou,1 Ping He3 1Department of Respiratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 2Department of Respiratory Medicine, Jiading Central Hospital, 3Department of Microbiology and Parasitology, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: Evidence suggests that suppressor of cytokine signaling 1 (SOCS1 is crucial for the negative regulation of inflammation. We investigated the relationship between smoking, SOCS1, and leukotriene B4 (LTB4 in vitro and in clinical samples of COPD; besides which we detected the impact of LTB4 receptor 1 (BLT1 antagonist on inflammation.Methods: SOCS1 expression in bronchial mucosa was determined by immunohistochemistry and real-time polymerase chain reaction. We also detect SOCS1 and BLT1 expression in alveolar macrophages from bronchoalveolar lavage fluid (BALF by real time-PCR, in addition to measuring the level of cytokines in BALF using enzyme-linked immunosorbent assay. In vitro, we investigated the expression of SOCS1 in cigarette smoke extract-induced mouse macrophage cell line RAW264.7 by real-time polymerase chain reaction and Western blot, and detected the level of cytokines in the supernatant by enzyme-linked immunosorbent assay. Then, we investigated the effects of BLT1 antagonist U-75302 on SOCS1 expression in these cells.Results: We obtained endobronchial biopsies (15 COPD patients and 12 non-COPD control subjects and BALF (20 COPD patients and 20 non-COPD control subjects, and our results showed that SOCS1 expression significantly decreased in lung tissues from COPD patients. Inflammatory cytokines in BALF were higher in COPD and these inflammatory cytokines negatively correlate with SOCS1 levels. Further, the BLT1 antagonist restored SOCS1 expression and in turn

  9. Novel computational methodologies for structural modeling of spacious ligand binding sites of G-protein-coupled receptors: development and application to human leukotriene B4 receptor.

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    Ishino, Yoko; Harada, Takanori

    2012-01-01

    This paper describes a novel method to predict the activated structures of G-protein-coupled receptors (GPCRs) with high accuracy, while aiming for the use of the predicted 3D structures in in silico virtual screening in the future. We propose a new method for modeling GPCR thermal fluctuations, where conformation changes of the proteins are modeled by combining fluctuations on multiple time scales. The core idea of the method is that a molecular dynamics simulation is used to calculate average 3D coordinates of all atoms of a GPCR protein against heat fluctuation on the picosecond or nanosecond time scale, and then evolutionary computation including receptor-ligand docking simulations functions to determine the rotation angle of each helix of a GPCR protein as a movement on a longer time scale. The method was validated using human leukotriene B4 receptor BLT1 as a sample GPCR. Our study demonstrated that the proposed method was able to derive the appropriate 3D structure of the active-state GPCR which docks with its agonists.

  10. Novel Computational Methodologies for Structural Modeling of Spacious Ligand Binding Sites of G-Protein-Coupled Receptors: Development and Application to Human Leukotriene B4 Receptor

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    Yoko Ishino

    2012-01-01

    Full Text Available This paper describes a novel method to predict the activated structures of G-protein-coupled receptors (GPCRs with high accuracy, while aiming for the use of the predicted 3D structures in in silico virtual screening in the future. We propose a new method for modeling GPCR thermal fluctuations, where conformation changes of the proteins are modeled by combining fluctuations on multiple time scales. The core idea of the method is that a molecular dynamics simulation is used to calculate average 3D coordinates of all atoms of a GPCR protein against heat fluctuation on the picosecond or nanosecond time scale, and then evolutionary computation including receptor-ligand docking simulations functions to determine the rotation angle of each helix of a GPCR protein as a movement on a longer time scale. The method was validated using human leukotriene B4 receptor BLT1 as a sample GPCR. Our study demonstrated that the proposed method was able to derive the appropriate 3D structure of the active-state GPCR which docks with its agonists.

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

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    Thomas E. Adrian

    2008-01-01

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

  12. Leukotriene B4 receptor 2 regulates the proliferation, migration, and barrier integrity of bronchial epithelial cells.

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    Liu, Min; Shen, Juan; Yuan, Huimin; Chen, Fengling; Song, Huaidong; Qin, Hui; Li, Yanqin; Xu, Jiabo; Ye, Qing; Li, Shenxian; Saeki, Kazuko; Yokomizo, Takehiko

    2018-01-11

    The airway epithelium plays a crucial role in the pathogenesis of asthma. The functions of leukotriene B4 receptor 2 (BLT2) on the airway epithelial cells remains unknown. In our study, BLT2 expression in 16HBE bronchial epithelial cells were manipulated by transfection with BLT2 overexpression plasmid or BLT2 small interference RNA. 16HBE cells were then exposed to BLT2 antagonist (LY255283) or BLT2 agonist (12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid [12-HHT] or CAY10583). The results showed that BLT2 overexpression, 12-HHT stimulation, or CAY10583 treatment resulted in the enhanced proliferation and migration of 16HBE cells. In addition, BLT2 showed an inhibitory effect on epithelial permeability as illustrated by the measurement of transepithelial electrical resistance (TER) and epithelial permeability, and a promoting effect on the levels of tight junction proteins (occludin and claudin-4) and phosphorylated p38 as demonstrated by real-time PCR and Western blotting analyses. These results suggest BLT2 as a key determinant of airway epithelial barrier integrity. On the contrary, RNAi-mediated knockdown or LY255283 treatment had reversed effects on the proliferation, migration, and epithelial barrier integrity. Together, our findings suggest the critical roles of BLT2 on the functions of bronchial epithelial cells and that BLT2 agonists are potential therapeutic agents for asthma treatment. © 2018 Wiley Periodicals, Inc.

  13. PEGylation potentiates the effectiveness of an antagonistic peptide that targets the EphB4 receptor with nanomolar affinity.

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    Roberta Noberini

    Full Text Available The EphB4 receptor tyrosine kinase together with its preferred ligand, ephrin-B2, regulates a variety of physiological and pathological processes, including tumor progression, pathological forms of angiogenesis, cardiomyocyte differentiation and bone remodeling. We previously reported the identification of TNYL-RAW, a 15 amino acid-long peptide that binds to the ephrin-binding pocked of EphB4 with low nanomolar affinity and inhibits ephrin-B2 binding. Although ephrin-B2 interacts promiscuously with all the EphB receptors, the TNYL-RAW peptide is remarkably selective and only binds to EphB4. Therefore, this peptide is a useful tool for studying the biological functions of EphB4 and for imaging EphB4-expressing tumors. Furthermore, TNYL-RAW could be useful for treating pathologies involving EphB4-ephrin-B2 interaction. However, the peptide has a very short half-life in cell culture and in the mouse blood circulation due to proteolytic degradation and clearance by the kidneys and reticuloendothelial system. To overcome these limitations, we have modified TNYL-RAW by fusion with the Fc portion of human IgG1, complexation with streptavidin or covalent coupling to a 40 KDa branched polyethylene glycol (PEG polymer. These modified forms of TNYL-RAW all have greatly increased stability in cell culture, while retaining high binding affinity for EphB4. Furthermore, PEGylation most effectively increases peptide half-life in vivo. Consistent with increased stability, submicromolar concentrations of PEGylated TNYL-RAW effectively impair EphB4 activation by ephrin-B2 in cultured B16 melanoma cells as well as capillary-like tube formation and capillary sprouting in co-cultures of endothelial and epicardial mesothelial cells. Therefore, PEGylated TNYL-RAW may be useful for inhibiting pathological forms of angiogenesis through a novel mechanism involving disruption of EphB4-ephrin-B2 interactions between endothelial cells and supporting perivascular mesenchymal

  14. Expression of the neuregulin receptor ErbB4 in the brain of the rhesus monkey (Macaca mulatta.

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    Jörg Neddens

    Full Text Available We demonstrated recently that frontal cortical expression of the Neuregulin (NRG receptor ErbB4 is restricted to interneurons in rodents, macaques, and humans. However, little is known about protein expression patterns in other areas of the brain. In situ hybridization studies have shown high ErbB4 mRNA levels in various subcortical areas, suggesting that ErbB4 is also expressed in cell types other than cortical interneurons. Here, using highly-specific monoclonal antibodies, we provide the first extensive report of ErbB4 protein expression throughout the cerebrum of primates. We show that ErbB4 immunoreactivity is high in association cortices, intermediate in sensory cortices, and relatively low in motor cortices. The overall immunoreactivity in the hippocampal formation is intermediate, but is high in a subset of interneurons. We detected the highest overall immunoreactivity in distinct locations of the ventral hypothalamus, medial habenula, intercalated nuclei of the amygdala and structures of the ventral forebrain, such as the islands of Calleja, olfactory tubercle and ventral pallidum, and medium expression in the reticular thalamic nucleus. While this pattern is generally consistent with ErbB4 mRNA expression data, further investigations are needed to identify the exact cellular and subcellular sources of mRNA and protein expression in these areas. In contrast to in situ hybridization in rodents, we detected only low levels of ErbB4-immunoreactivity in mesencephalic dopaminergic nuclei but a diffuse pattern of immunofluorescence that was medium in the dorsal striatum and high in the ventral forebrain, suggesting that most ErbB4 protein in dopaminergic neurons could be transported to axons. We conclude that the NRG-ErbB4 signaling pathway can potentially influence many functional systems throughout the brain of primates, and suggest that major sites of action are areas of the "corticolimbic" network. This interpretation is functionally

  15. Analysis of copy number loss of the ErbB4 receptor tyrosine kinase in glioblastoma.

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    Jones, DeAnalisa C; Scanteianu, Adriana; DiStefano, Matthew; Bouhaddou, Mehdi; Birtwistle, Marc R

    2018-01-01

    Current treatments for glioblastoma multiforme (GBM)-an aggressive form of brain cancer-are minimally effective and yield a median survival of 14.6 months and a two-year survival rate of 30%. Given the severity of GBM and the limitations of its treatment, there is a need for the discovery of novel drug targets for GBM and more personalized treatment approaches based on the characteristics of an individual's tumor. Most receptor tyrosine kinases-such as EGFR-act as oncogenes, but publicly available data from the Cancer Cell Line Encyclopedia (CCLE) indicates copy number loss in the ERBB4 RTK gene across dozens of GBM cell lines, suggesting a potential tumor suppressor role. This loss is mutually exclusive with loss of its cognate ligand NRG1 in CCLE as well, more strongly suggesting a functional role. The availability of higher resolution copy number data from clinical GBM patients in The Cancer Genome Atlas (TCGA) revealed that a region in Intron 1 of the ERBB4 gene was deleted in 69.1% of tumor samples harboring ERBB4 copy number loss; however, it was also found to be deleted in the matched normal tissue samples from these GBM patients (n = 81). Using the DECIPHER Genome Browser, we also discovered that this mutation occurs at approximately the same frequency in the general population as it does in the disease population. We conclude from these results that this loss in Intron 1 of the ERBB4 gene is neither a de novo driver mutation nor a predisposing factor to GBM, despite the indications from CCLE. A biological role of this significantly occurring genetic alteration is still unknown. While this is a negative result, the broader conclusion is that while copy number data from large cell line-based data repositories may yield compelling hypotheses, careful follow up with higher resolution copy number assays, patient data, and general population analyses are essential to codify initial hypotheses prior to investing experimental resources.

  16. Analysis of copy number loss of the ErbB4 receptor tyrosine kinase in glioblastoma.

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    DeAnalisa C Jones

    Full Text Available Current treatments for glioblastoma multiforme (GBM-an aggressive form of brain cancer-are minimally effective and yield a median survival of 14.6 months and a two-year survival rate of 30%. Given the severity of GBM and the limitations of its treatment, there is a need for the discovery of novel drug targets for GBM and more personalized treatment approaches based on the characteristics of an individual's tumor. Most receptor tyrosine kinases-such as EGFR-act as oncogenes, but publicly available data from the Cancer Cell Line Encyclopedia (CCLE indicates copy number loss in the ERBB4 RTK gene across dozens of GBM cell lines, suggesting a potential tumor suppressor role. This loss is mutually exclusive with loss of its cognate ligand NRG1 in CCLE as well, more strongly suggesting a functional role. The availability of higher resolution copy number data from clinical GBM patients in The Cancer Genome Atlas (TCGA revealed that a region in Intron 1 of the ERBB4 gene was deleted in 69.1% of tumor samples harboring ERBB4 copy number loss; however, it was also found to be deleted in the matched normal tissue samples from these GBM patients (n = 81. Using the DECIPHER Genome Browser, we also discovered that this mutation occurs at approximately the same frequency in the general population as it does in the disease population. We conclude from these results that this loss in Intron 1 of the ERBB4 gene is neither a de novo driver mutation nor a predisposing factor to GBM, despite the indications from CCLE. A biological role of this significantly occurring genetic alteration is still unknown. While this is a negative result, the broader conclusion is that while copy number data from large cell line-based data repositories may yield compelling hypotheses, careful follow up with higher resolution copy number assays, patient data, and general population analyses are essential to codify initial hypotheses prior to investing experimental resources.

  17. NK cell cytotoxicity mediated by 2B4 and NTB-A is dependent on SAP acting downstream of receptor phosphorylation

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    Stephan eMeinke

    2013-01-01

    Full Text Available 2B4 (CD244 and NK-T-B-antigen (NTB-A, CD352 are activating receptors on human NK cells and belong to the family of SLAM-related receptors. Engagement of these receptors leads to phosphorylation of their cytoplasmic tails and recruitment of the adapter proteins SAP and EAT-2. X-linked lymphoproliferative syndrome (XLP is a severe immunodeficiency that results from mutations in the SAP gene. 2B4 and NTB-A-mediated cytotoxicity are abrogated in XLP NK cells. To elucidate the molecular basis for this defect we analyzed early signaling events in SAP knockdown cells. Similar to XLP NK cells, knockdown of SAP in primary human NK cells leads to a reduction of 2B4 and NTB-A-mediated cytotoxicity. We found that early signaling events such as raft recruitment and receptor phosphorylation are not affected by the absence of SAP, indicating the defect in the absence of SAP is downstream of these events. In addition, knockdown of EAT-2 does not impair 2B4 or NTB-A-mediated cytotoxicity. Surprisingly, EAT-2 recruitment to both receptors is abrogated in the absence of SAP, revealing a novel cooperativity between these adapters.

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

    International Nuclear Information System (INIS)

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

    2003-01-01

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

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

    International Nuclear Information System (INIS)

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

    1986-01-01

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

  20. Toll-like receptor 3 is critical for coxsackievirus B4-induced type 1 diabetes in female NOD mice.

    Science.gov (United States)

    McCall, Kelly D; Thuma, Jean R; Courreges, Maria C; Benencia, Fabian; James, Calvin B L; Malgor, Ramiro; Kantake, Noriko; Mudd, William; Denlinger, Nathan; Nolan, Bret; Wen, Li; Schwartz, Frank L

    2015-02-01

    Group B coxsackieviruses (CVBs) are involved in triggering some cases of type 1 diabetes mellitus (T1DM). However, the molecular mechanism(s) responsible for this remain elusive. Toll-like receptor 3 (TLR3), a receptor that recognizes viral double-stranded RNA, is hypothesized to play a role in virus-induced T1DM, although this hypothesis is yet to be substantiated. The objective of this study was to directly investigate the role of TLR3 in CVB-triggered T1DM in nonobese diabetic (NOD) mice, a mouse model of human T1DM that is widely used to study both spontaneous autoimmune and viral-induced T1DM. As such, we infected female wild-type (TLR3(+/+)) and TLR3 knockout (TLR3(-/-)) NOD mice with CVB4 and compared the incidence of diabetes in CVB4-infected mice with that of uninfected counterparts. We also evaluated the islets of uninfected and CVB4-infected wild-type and TLR3 knockout NOD mice by immunohistochemistry and insulitis scoring. TLR3 knockout mice were markedly protected from CVB4-induced diabetes compared with CVB4-infected wild-type mice. CVB4-induced T-lymphocyte-mediated insulitis was also significantly less severe in TLR3 knockout mice compared with wild-type mice. No differences in insulitis were observed between uninfected animals, either wild-type or TLR3 knockout mice. These data demonstrate for the first time that TLR3 is 1) critical for CVB4-induced T1DM, and 2) modulates CVB4-induced insulitis in genetically prone NOD mice.

  1. Novel Computational Methodologies for Structural Modeling of Spacious Ligand Binding Sites of G-Protein-Coupled Receptors: Development and Application to Human Leukotriene B4 Receptor

    OpenAIRE

    Ishino, Yoko; Harada, Takanori

    2012-01-01

    This paper describes a novel method to predict the activated structures of G-protein-coupled receptors (GPCRs) with high accuracy, while aiming for the use of the predicted 3D structures in in silico virtual screening in the future. We propose a new method for modeling GPCR thermal fluctuations, where conformation changes of the proteins are modeled by combining fluctuations on multiple time scales. The core idea of the method is that a molecular dynamics simulation is used to calculate avera...

  2. N-(2,4)-dinitrophenyl-L-arginine Interacts with EphB4 and Functions as an EphB4 Kinase Modulator.

    Science.gov (United States)

    Kamstra, Rhiannon L; Freywald, Andrew; Floriano, Wely B

    2015-10-01

    The erythropoietin-producing hepatocellular carcinoma receptor B4 is a receptor tyrosine kinase whose expression is preserved in various malignancies, including colon, gastric, and breast carcinoma. Hepatocellular carcinoma receptor B4 presence in tumor cells and involvement in cancer suppression makes it a potential therapeutic target for activating compounds. Moreover, modulators of its activity also have a strong potential to be used in diagnosis and therapy monitoring. We used virtual ligand screening to identify novel hepatocellular carcinoma receptor B4 kinase modulators for experimental testing. Three independent assay platforms confirmed that dinitrophenyl-L-arginine is likely to affect the kinase activity of hepatocellular carcinoma receptor B4. An enzyme-coupled spectrophotometric assay has been used to examine this possibility and may prove to be useful for assessing other novel kinase modulator candidates. Overall, our observations suggest that dinitrophenyl-L-arginine has an activating effect on hepatocellular carcinoma receptor B4 and, therefore, more efficient derivatives may have therapeutic effects in tumors where hepatocellular carcinoma receptor B4 exhibits antimalignant properties. The hepatocellular carcinoma receptor B4-activating effect is discussed with respect to previously described mechanisms, using predicted and experimental structures for docked ligands. As a novel kinase activity modulator, dinitrophenyl-L-arginine may provide new insights into molecular mechanisms by which kinases are activated or regulated, and may serve as a lead compound for the generation of novel hepatocellular carcinoma receptor B4-activating therapeutic compounds. © 2014 John Wiley & Sons A/S.

  3. 7 CFR 15b.4 - Discrimination prohibited.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Discrimination prohibited. 15b.4 Section 15b.4... ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE General Provisions § 15b.4 Discrimination prohibited. (a... in, be denied the benefits of, or otherwise be subjected to discrimination under any program or...

  4. 15 CFR 8b.4 - Discrimination prohibited.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Discrimination prohibited. 8b.4 Section 8b.4 Commerce and Foreign Trade Office of the Secretary of Commerce PROHIBITION OF DISCRIMINATION... Provisions § 8b.4 Discrimination prohibited. (a) General. No qualified handicapped individual shall, on the...

  5. 18 CFR 3b.4 - Government contractors.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Government contractors. 3b.4 Section 3b.4 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION... PERSONAL INFORMATION General § 3b.4 Government contractors. Systems of records operated by a contractor...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-01-29

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

  7. EphB4 localises to the nucleus of prostate cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Mertens-Walker, Inga, E-mail: inga.mertenswalker@qut.edu.au [Institute of Health and Biomedical Innovation, Queensland University of Technology, Woolloongabba, QLD (Australia); Australian Prostate Cancer Research Centre—Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba 4102, QLD (Australia); Lisle, Jessica E. [Institute of Health and Biomedical Innovation, Queensland University of Technology, Woolloongabba, QLD (Australia); Australian Prostate Cancer Research Centre—Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba 4102, QLD (Australia); Nyberg, William A. [Institute of Health and Biomedical Innovation, Queensland University of Technology, Woolloongabba, QLD (Australia); Stephens, Carson R. [Institute of Health and Biomedical Innovation, Queensland University of Technology, Woolloongabba, QLD (Australia); Australian Prostate Cancer Research Centre—Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba 4102, QLD (Australia); Burke, Leslie [Institute of Health and Biomedical Innovation, Queensland University of Technology, Woolloongabba, QLD (Australia); Rutkowski, Raphael; Herington, Adrian C.; Stephenson, Sally-Anne [Institute of Health and Biomedical Innovation, Queensland University of Technology, Woolloongabba, QLD (Australia); Australian Prostate Cancer Research Centre—Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba 4102, QLD (Australia)

    2015-04-10

    The EphB4 receptor tyrosine kinase is over-expressed in a variety of different epithelial cancers including prostate where it has been shown to be involved in survival, migration and angiogenesis. We report here that EphB4 also resides in the nucleus of prostate cancer cell lines. We used in silico methods to identify a bipartite nuclear localisation signal (NLS) in the extracellular domain and a monopartite NLS sequence in the intracellular kinase domain of EphB4. To determine whether both putative NLS sequences were functional, fragments of the EphB4 sequence containing each NLS were cloned to create EphB4NLS-GFP fusion proteins. Localisation of both NLS-GFP proteins to the nuclei of transfected cells was observed, demonstrating that EphB4 contains two functional NLS sequences. Mutation of the key amino residues in both NLS sequences resulted in diminished nuclear accumulation. As nuclear translocation is often dependent on importins we confirmed that EphB4 and importin-α can interact. To assess if nuclear EphB4 could be implicated in gene regulatory functions potential EphB4-binding genomic loci were identified using chromatin immunoprecipitation and Lef1 was confirmed as a potential target of EphB4-mediated gene regulation. These novel findings add further complexity to the biology of this important cancer-associated receptor. - Highlights: • The EphB4 protein can be found in the nucleus of prostate cancer cell lines. • EphB4 contains two functional nuclear localisation signals. • Chromatin immunoprecipitation has identified potential genome sequences to which EphB4 binds. • Lef1 is a confirmed target for EphB4-mediated gene regulation.

  8. EphB4 localises to the nucleus of prostate cancer cells

    International Nuclear Information System (INIS)

    Mertens-Walker, Inga; Lisle, Jessica E.; Nyberg, William A.; Stephens, Carson R.; Burke, Leslie; Rutkowski, Raphael; Herington, Adrian C.; Stephenson, Sally-Anne

    2015-01-01

    The EphB4 receptor tyrosine kinase is over-expressed in a variety of different epithelial cancers including prostate where it has been shown to be involved in survival, migration and angiogenesis. We report here that EphB4 also resides in the nucleus of prostate cancer cell lines. We used in silico methods to identify a bipartite nuclear localisation signal (NLS) in the extracellular domain and a monopartite NLS sequence in the intracellular kinase domain of EphB4. To determine whether both putative NLS sequences were functional, fragments of the EphB4 sequence containing each NLS were cloned to create EphB4NLS-GFP fusion proteins. Localisation of both NLS-GFP proteins to the nuclei of transfected cells was observed, demonstrating that EphB4 contains two functional NLS sequences. Mutation of the key amino residues in both NLS sequences resulted in diminished nuclear accumulation. As nuclear translocation is often dependent on importins we confirmed that EphB4 and importin-α can interact. To assess if nuclear EphB4 could be implicated in gene regulatory functions potential EphB4-binding genomic loci were identified using chromatin immunoprecipitation and Lef1 was confirmed as a potential target of EphB4-mediated gene regulation. These novel findings add further complexity to the biology of this important cancer-associated receptor. - Highlights: • The EphB4 protein can be found in the nucleus of prostate cancer cell lines. • EphB4 contains two functional nuclear localisation signals. • Chromatin immunoprecipitation has identified potential genome sequences to which EphB4 binds. • Lef1 is a confirmed target for EphB4-mediated gene regulation

  9. Synthetic and structure/activity studies on acid-substituted 2-arylphenols: discovery of 2-[2-propyl-3-[3-[2-ethyl-4-(4-fluorophenyl)-5- hydroxyphenoxy]-propoxy]phenoxy]benzoic acid, a high-affinity leukotriene B4 receptor antagonist.

    Science.gov (United States)

    Sawyer, J S; Bach, N J; Baker, S R; Baldwin, R F; Borromeo, P S; Cockerham, S L; Fleisch, J H; Floreancig, P; Froelich, L L; Jackson, W T

    1995-10-27

    Structural derivatives of LY255283 have been studied as receptor antagonists of leukotriene B4. Substitution of the 2-hydroxyacetophenone subunit of 1 (LY255283) with a 2-arylphenol group provided entry into several new series that feature various mono- and diacidic core functionality. These new analogues, the subject of a broad structure-activity investigation, displayed significantly increased in vitro and in vivo activity as receptor antagonists of LTB4. A series of diaryl ether carboxylic acids demonstrated especially interesting activity and led to the discovery of compound 43b, 2-[2-propyl-3-[3-[2-ethyl-4-(4- fluorophenyl)-5-hydroxyphenoxy]-propoxy]phenoxy]benzoic acid (LY293111), a 2-arylphenol-substituted diaryl ether carboxylic acid which displayed potent binding to human neutrophils (IC50 = 17 +/- 4.6 nM) and guinea pig lung membranes (IC50 = 6.6 +/- 0.71 nM), inhibition of LTB4-induced expression of the CD11b/CD18 receptor on human neutrophils (IC50 = 3.3 +/- 0.81 nM), and inhibition of LTB4-induced contraction of guinea pig lung parenchyma (pKB = 8.7 +/- 0.16). In vivo, 43b demonstrated potent activity in inhibiting LTB4-induced airway obstruction in the guinea pig when dosed by the oral (ED50 = 0.40 mg/kg) or intravenous (ED50 = 0.014 mg/kg) routes. A specific LTB4 receptor antagonist, 43b had little effect on inhibiting contractions of guinea pig lung parenchyma induced by leukotriene D4 (LTD4), histamine, carbachol, or U46619. Compound 43b has been chosen as a clinical candidate and is currently in phase I studies for a variety of inflammatory diseases.

  10. EphB4 Receptor Tyrosine Kinase in Prostate Cancer

    Science.gov (United States)

    2011-09-01

    Y. Hwang, J. Chen, J. Biol. Chem. 282 (2007) 2683. [51] L.S. Spofford, E.V. Abel , K. Boisvert-Adamo, A.E. Aplin, J. Biol. Chem. 281 (2006) 25644. [52...Biol. 23 (2003) 9389. [77] S.D. Narasimhan, A. Mukhopadhyay, H.A. Tissenbaum, Cell Cycle 8 (2009) 3878. [78] M.M. Santoro, G. Gaudino, E. Villa -Moruzzi

  11. Effect of increased HoxB4 on human megakaryocytic development

    Energy Technology Data Exchange (ETDEWEB)

    Zhong, Yiming [Department of Pathology, The Ohio State University, Columbus, OH (United States); Program in Molecular, Cellular, and Developmental Biology, The Ohio State University, Columbus, OH (United States); Sullenbarger, Brent [Department of Pathology, The Ohio State University, Columbus, OH (United States); Lasky, Larry C., E-mail: Lasky.4@osu.edu [Department of Pathology, The Ohio State University, Columbus, OH (United States); Program in Molecular, Cellular, and Developmental Biology, The Ohio State University, Columbus, OH (United States)

    2010-07-30

    Research highlights: {yields} HoxB4 overexpression in human TF1 cells increased the expression of CD61 and CD41a. {yields} HoxB4 fusion protein enhanced megakaryocytic development of CD34{sup +} cord blood cells. {yields} Ectopic HoxB4 increased Tpo receptor expression and decreased c-Myb expression. {yields} HoxB4 RNA silencing increased c-Myb expression and decreased Fli-1 expression. -- Abstract: In order to produce clinically useful quantities of platelets ex vivo we may need to firstly enhance early self-renewal of hematopoietic stem cells (HSCs) and/or megakaryocyte (Mk) progenitors. The homeodomain transcription factor HoxB4 has been shown to be an important regulator of stem cell renewal and hematopoiesis; however, its effect on megakaryopoiesis is unclear. In this study, we investigated the effect of HoxB4 overexpression or RNA silencing on megakaryocytic development in the human TF1 progenitor cell line; we then used recombinant tPTD-HoxB4 fusion protein to study the effect of exogenous HoxB4 on megakaryocytic development of human CD34 positively-selected cord blood cells. We found that ectopic HoxB4 in TF1 cells increased the antigen expression of CD61and CD41a, increased the gene expression of thrombopoietin receptor (TpoR), Scl-1, Cyclin D1, Fog-1 and Fli-1 while it decreased c-Myb expression. HoxB4 RNA silencing in TF1 cells decreased the expression of CD61 and CD41a and decreased Fli-1 expression while it increased the expression of c-Myb. Recombinant tPTD-HoxB4 fusion protein increased the percentages and absolute numbers of CD41a and CD61 positive cells during megakaryocytic differentiation of CD34 positively-selected cord blood cells and increased the numbers of colony-forming unit-megakaryocyte (CFU-Mk). Adding tPTD-HoxB4 fusion protein increased the gene expression of TpoR, Cyclin D1, Fog-1 and Fli-1 while it inhibited c-Myb expression. Our data suggest that increased HoxB4 enhanced early megakaryocytic development in human TF1 cells and CD34

  12. Effect of increased HoxB4 on human megakaryocytic development

    International Nuclear Information System (INIS)

    Zhong, Yiming; Sullenbarger, Brent; Lasky, Larry C.

    2010-01-01

    Research highlights: → HoxB4 overexpression in human TF1 cells increased the expression of CD61 and CD41a. → HoxB4 fusion protein enhanced megakaryocytic development of CD34 + cord blood cells. → Ectopic HoxB4 increased Tpo receptor expression and decreased c-Myb expression. → HoxB4 RNA silencing increased c-Myb expression and decreased Fli-1 expression. -- Abstract: In order to produce clinically useful quantities of platelets ex vivo we may need to firstly enhance early self-renewal of hematopoietic stem cells (HSCs) and/or megakaryocyte (Mk) progenitors. The homeodomain transcription factor HoxB4 has been shown to be an important regulator of stem cell renewal and hematopoiesis; however, its effect on megakaryopoiesis is unclear. In this study, we investigated the effect of HoxB4 overexpression or RNA silencing on megakaryocytic development in the human TF1 progenitor cell line; we then used recombinant tPTD-HoxB4 fusion protein to study the effect of exogenous HoxB4 on megakaryocytic development of human CD34 positively-selected cord blood cells. We found that ectopic HoxB4 in TF1 cells increased the antigen expression of CD61and CD41a, increased the gene expression of thrombopoietin receptor (TpoR), Scl-1, Cyclin D1, Fog-1 and Fli-1 while it decreased c-Myb expression. HoxB4 RNA silencing in TF1 cells decreased the expression of CD61 and CD41a and decreased Fli-1 expression while it increased the expression of c-Myb. Recombinant tPTD-HoxB4 fusion protein increased the percentages and absolute numbers of CD41a and CD61 positive cells during megakaryocytic differentiation of CD34 positively-selected cord blood cells and increased the numbers of colony-forming unit-megakaryocyte (CFU-Mk). Adding tPTD-HoxB4 fusion protein increased the gene expression of TpoR, Cyclin D1, Fog-1 and Fli-1 while it inhibited c-Myb expression. Our data suggest that increased HoxB4 enhanced early megakaryocytic development in human TF1 cells and CD34 positively-selected cord

  13. Involvement of the BLT2 receptor in the itch-associated scratching induced by 12-(S)-lipoxygenase products in ICR mice.

    Science.gov (United States)

    Kim, H J; Kim, D K; Kim, H; Koh, J Y; Kim, K M; Noh, M S; Lee, S; Kim, S; Park, S H; Kim, J J; Kim, S Y; Lee, C H

    2008-07-01

    Recently, we reported that 12(S)-HPETE (12(S)-hydroperoxyeicosa-5Z,8Z,10E,14Z-tetraenoic acid) induces scratching in ICR mice. We hypothesized that 12(S)-HPETE might act as an agonist of the low-affinity leukotriene B4 receptor BLT2. To confirm the involvement of the BLT2 receptor in 12(S)-HPETE-induced scratching, we studied the scratch response using the BLT2 receptor agonists compound A (4'-[[pentanoyl (phenyl) amino]methyl]-1,1'-biphenyl-2-carboxylic acid) and 12(S)-HETE (12(S)-hydroxyeicosa-5Z,8Z,10E,14Z-tetraenoic acid). A video recording was used to determine whether the BLT2 receptor agonists caused itch-associated scratching in ICR mice. Selective antagonists and several chemicals were used. Both 12(S)-HETE and compound A dose dependently induced scratching in the ICR mice. The dose-response curve for compound A showed peaks at around 0.005-0.015 nmol per site. Compound A- and 12(S)-HETE-induced scratching was suppressed by capsaicin and naltrexon. We examined the suppressive effects of U75302 (6-[6-(3-hydroxy-1E,5Z-undecadienyl)-2-pyridinyl]-1,5-hexanediol, the BLT1 receptor antagonist) and LY255283 (1-[5-ethyl-2-hydroxy-4-[[6-methyl-6-(1H-tetrazol-5-yl)heptyl]oxy]phenyl]-ethanone, the BLT2 receptor antagonist) on the BLT2 agonist-induced scratching. LY255283 suppressed compound A- and 12(S)-HETE-induced scratching, but U75302 did not. LY255283 required a higher dose to suppress the compound A-induced scratching than it did to suppress the 12(S)-HETE-induced scratching. One of the BLT(2) receptor agonists, 12(R)-HETE (12(R)-hydroxyeicosa-5Z,8Z,10E,14Z-tetraenoic acid), also induced scratching in the ICR mice. Our present results corroborate the hypothesis that the BLT2 receptor is involved in 12(S)-lipoxygenase-product-induced scratching in ICR mice. We also confirmed that this animal model could be a valuable means of evaluating the effects of BLT2 receptor antagonists.

  14. EphB4/EphrinB2 therapeutics in Rhabdomyosarcoma.

    Directory of Open Access Journals (Sweden)

    Matthew E Randolph

    Full Text Available Rhabdomyosarcoma (RMS is the most common soft tissue sarcoma affecting children and is often diagnosed with concurrent metastases. Unfortunately, few effective therapies have been discovered that improve the long-term survival rate for children with metastatic disease. Here we determined effectiveness of targeting the receptor tyrosine kinase, EphB4, in both alveolar and embryonal RMS either directly through the inhibitory antibody, VasG3, or indirectly by blocking both forward and reverse signaling of EphB4 binding to EphrinB2, cognate ligand of EphB4. Clinically, EphB4 expression in eRMS was correlated with longer survival. Experimentally, inhibition of EphB4 with VasG3 in both aRMS and eRMS orthotopic xenograft and allograft models failed to alter tumor progression. Inhibition of EphB4 forward signaling using soluble EphB4 protein fused with murine serum albumin failed to affect eRMS model tumor progression, but did moderately slow progression in murine aRMS. We conclude that inhibition of EphB4 signaling with these agents is not a viable monotherapy for rhabdomyosarcoma.

  15. Inhibition of Tumor Growth and Angiogenesis by Soluble EphB4

    Directory of Open Access Journals (Sweden)

    Georg Martiny-Baron

    2004-05-01

    Full Text Available EphB receptors and their ephrinB ligands play a key role in the formation of a regular vascular system. Recent studies have also shown the involvement of Eph/ephrin interactions in malignant tumor progression and angiogenesis. We have generated soluble monomeric EphB4 (sEphB4-expressing A375 melanoma cells to study the effect of dominant negatively acting sEphB4 on tumor growth and angiogenesis. Soluble EphB4-expressing A375 tumors grown subcutaneously in nude mice show dramatically reduced tumor growth compared to control tumors. The proliferative capacity of sEphB4-expressing cells in monolayer culture is not altered. Yet, sEphB4-expressing A375 cells cannot establish proper cell-cell contacts in three-dimensional spheroids. However, sEphB4 transfectants have reduced proliferation and apoptosis rates when grown in three-dimensional culture in vitro or in subcutaneous tumors in vivo. Analysis of the vascular phenotype of the tumors revealed a reduction of intratumoral microvessel density in sEphB4-expressing tumors. Corresponding to these mouse experiments, a matched pair analysis of EphB4 and ephrinB2 expression in human colon carcinomas revealed significantly upregulated levels of EphB4 expression compared to adjacent normal tissue. Taken together, the data identify dual effects of sEphB4 on the tumor and the vascular compartment that collectively inhibit tumor growth.

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

    International Nuclear Information System (INIS)

    Jiang Guojian; Xu Jiayue; Zhuang Hanrui; Li Wenlan

    2009-01-01

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

  17. Upregulation of Leukotriene Receptors in Gastric Cancer

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-08-08

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

  18. FXR induces the UGT2B4 enzyme in hepatocytes: a potential mechanism of negative feedback control of FXR activity.

    Science.gov (United States)

    Barbier, Olivier; Torra, Ines Pineda; Sirvent, Audrey; Claudel, Thierry; Blanquart, Christophe; Duran-Sandoval, Daniel; Kuipers, Folkert; Kosykh, Vladimir; Fruchart, Jean-Charles; Staels, Bart

    2003-06-01

    Bile acids are essential for bile formation and intestinal absorption of lipids and fat-soluble vitamins. However, the intrinsic toxicity of hydrophobic bile acids demands a tight control of their intracellular concentrations. Bile acids are ligands for the farnesoid X receptor (FXR) that regulates the expression of genes controlling bile acid synthesis and transport. The human uridine 5'-diphosphate-glucuronosyltransferase 2B4 (UGT2B4) converts hydrophobic bile acids into more hydrophilic glucuronide derivatives. In this study, we identify UGT2B4 as an FXR target gene. Human hepatocytes or hepatoblastoma HepG2 cells were treated with chenodeoxycholic acid or the synthetic FXR agonist GW4064, and the levels of UGT2B4 messenger RNA, protein, and activity were determined by using real-time polymerase chain reaction, Western blot, and glucuronidation assays. Treatment of hepatocytes and HepG2 cells with FXR agonists resulted in an increase of UGT2B4 messenger RNA, protein, and activity. A bile acid response element in the UGT2B4 promoter (B4-BARE) to which FXR, but not retinoid X receptor, binds, was identified by site-directed mutagenesis, electromobility shift, and chromatin immunoprecipitation assays. Retinoid X receptor activation abolished the induction of UGT2B4 expression and inhibited binding of FXR to the B4-BARE, suggesting that retinoid X receptor modulates FXR target gene activation. Overexpression of UGT2B4 in HepG2 cells resulted in the attenuation of bile acid induction of the FXR target gene small heterodimeric partner. These data suggest that UGT2B4 gene induction by bile acids contributes to a feed-forward reduction of bile acid toxicity and a decrease of the activity of these biological FXR activators.

  19. Evolving role of 2B4/CD244 in T and NK cell responses during virus infection

    Directory of Open Access Journals (Sweden)

    Stephen Noel Waggoner

    2012-12-01

    Full Text Available The signaling lymphocyte activation molecule (SLAM family receptor, 2B4/CD244, was first implicated in anti-viral immunity by the discovery that mutations of the SLAM-associated protein, SAP/SH2D1A, impaired 2B4-dependent stimulation of T and natural killer (NK cell anti-viral functions in X-linked lymphoproliferative (XLP syndrome patients with uncontrolled Epstein-Barr virus (EBV infections. Engagement of 2B4 has been variably shown to either activate or inhibit lymphocytes which express this receptor. While SAP expression is required for stimulatory functions of 2B4 on lymphocytes, it remains unclear whether inhibitory signals derived from 2B4 can predominate even in the presence of SAP. Regardless, mounting evidence suggests that 2B4 expression by NK and CD8 T cells is altered by virus infection in mice as well as in humans, and 2B4-mediated signaling may be an important determinant of effective immune control of chronic virus infections. In this review, recent findings regarding the expression and function of 2B4 as well as SAP on T and NK cells during virus infection is discussed, with a focus on the role of 2B4-CD48 interactions in crosstalk between innate and adaptive immunity.

  20. 26 CFR 1.50B-4 - Partnerships.

    Science.gov (United States)

    2010-04-01

    ... § 1.50A-3, or if the partnership fails to pay comparable wages and such failure is subject to the... 26 Internal Revenue 1 2010-04-01 2010-04-01 true Partnerships. 1.50B-4 Section 1.50B-4 Internal... Credit for Expenses of Work Incentive Programs § 1.50B-4 Partnerships. (a) General rule—(1) In general...

  1. EphB4 as a therapeutic target in mesothelioma

    International Nuclear Information System (INIS)

    Liu, Ren; Ferguson, Benjamin D; Zhou, Yue; Naga, Kranthi; Salgia, Ravi; Gill, Parkash S; Krasnoperov, Valery

    2013-01-01

    Malignant pleural mesothelioma (MPM) often develops decades following exposure to asbestos. Current best therapy produces a response in only half of patients, and the median survival with this therapy remains under a year. A search for novel targets and therapeutics is underway, and recently identified targets include VEGF, Notch, and EphB4-Ephrin-B2. Each of these targets has dual activity, promoting tumor cell growth as well as tumor angiogenesis. We investigated EphB4 expression in 39 human mesothelioma tissues by immunohistochemistry. Xenograft tumors established with human mesothelioma cells were treated with an EphB4 inhibitor (monomeric soluble EphB4 fused to human serum albumin, or sEphB4-HSA). The combinatorial effect of sEphB4-HSA and biologic agent was also studied. EphB4 was overexpressed in 72% of mesothelioma tissues evaluated, with 85% of epithelioid and 38% of sarcomatoid subtypes demonstrating overexpression. The EphB4 inhibitor sEphB4-HSA was highly active as a single agent to inhibit tumor growth, accompanied by tumor cell apoptosis and inhibition of PI3K and Src signaling. Combination of sEphB4-HSA and the anti-VEGF antibody (Bevacizumab) was superior to each agent alone and led to complete tumor regression. EphB4 is a potential therapeutic target in mesothelioma. Clinical investigation of sEphB4-HSA as a single agent and in combination with VEGF inhibitors is warranted

  2. ErbB4 localization to cardiac myocyte nuclei, and its role in myocyte DNA damage response

    Energy Technology Data Exchange (ETDEWEB)

    Icli, Basak [Department of Medicine, Cardiovascular Division, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA 02115 (United States); Bharti, Ajit [Center of Molecular Stress Response Whitaker Cardiovascular Institute, Department of Medicine, Boston University Medical Center, Boston, MA 02118 (United States); Pentassuglia, Laura; Peng, Xuyang [Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (United States); Sawyer, Douglas B., E-mail: douglas.b.sawyer@vanderbilt.edu [Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (United States)

    2012-02-03

    Highlights: Black-Right-Pointing-Pointer ErbB4 localizes to cardiac myocyte nuclei as a full-length receptor. Black-Right-Pointing-Pointer Cardiac myocytes express predominantly JM-a/CYT-1 ErbB4. Black-Right-Pointing-Pointer Myocyte p53 activation in response to doxorubicin requires ErbB4 activity. -- Abstract: The intracellular domain of ErbB4 receptor tyrosine kinase is known to translocate to the nucleus of cells where it can regulate p53 transcriptional activity. The purpose of this study was to examine whether ErbB4 can localize to the nucleus of adult rat ventricular myocytes (ARVM), and regulate p53 in these cells. We demonstrate that ErbB4 does locate to the nucleus of cardiac myocytes as a full-length protein, although nuclear location occurs as a full-length protein that does not require Protein Kinase C or {gamma}-secretase activity. Consistent with this we found that only the non-cleavable JM-b isoform of ErbB4 is expressed in ARVM. Doxorubicin was used to examine ErbB4 role in regulation of a DNA damage response in ARVM. Doxorubicin induced p53 and p21 was suppressed by treatment with AG1478, an EGFR and ErbB4 kinase inhibitor, or suppression of ErbB4 expression with small interfering RNA. Thus ErbB4 localizes to the nucleus as a full-length protein, and plays a role in the DNA damage response induced by doxorubicin in cardiac myocytes.

  3. 26 CFR 54.4980B-4 - Qualifying events.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 17 2010-04-01 2010-04-01 false Qualifying events. 54.4980B-4 Section 54.4980B... EXCISE TAXES (CONTINUED) PENSION EXCISE TAXES § 54.4980B-4 Qualifying events. The determination of what constitutes a qualifying event is addressed in the following questions and answers: Q-1: What is a qualifying...

  4. Boron carbide (B4C) coating. Deposition and testing

    Science.gov (United States)

    Azizov, E.; Barsuk, V.; Begrambekov, L.; Buzhinsky, O.; Evsin, A.; Gordeev, A.; Grunin, A.; Klimov, N.; Kurnaev, V.; Mazul, I.; Otroshchenko, V.; Putric, A.; Sadovskiy, Ya.; Shigin, P.; Vergazov, S.; Zakharov, A.

    2015-08-01

    Boron carbide was proposed as a material of in-situ protecting coating for tungsten tiles of ITER divertor. To prove this concept the project including investigation of regimes of plasma deposition of B4C coating on tungsten and tests of boron carbide layer in ITER-like is started recently. The paper contends the first results of the project. The results of B4C coating irradiation by the plasma pulses of QSPU-T plasma accelerator are presented. The new device capable of B4C film deposition on tungsten and testing of the films and materials with ITER-like heat loads and ion- and electron irradiation is described. The results of B4C coating deposition and testing of both tungsten substrate and coating are shown and discussed.

  5. Characterization of LysB4, an endolysin from the Bacillus cereus-infecting bacteriophage B4.

    Science.gov (United States)

    Son, Bokyung; Yun, Jiae; Lim, Jeong-A; Shin, Hakdong; Heu, Sunggi; Ryu, Sangryeol

    2012-03-15

    Bacillus cereus is a foodborne pathogen that causes emetic or diarrheal types of food poisoning. The incidence of B. cereus food poisoning has been gradually increasing over the past few years, therefore, biocontrol agents effective against B. cereus need to be developed. Endolysins are phage-encoded bacterial peptidoglycan hydrolases and have received considerable attention as promising antibacterial agents. The endolysin from B. cereus phage B4, designated LysB4, was identified and characterized. In silico analysis revealed that this endolysin had the VanY domain at the N terminus as the catalytic domain, and the SH3_5 domain at the C terminus that appears to be the cell wall binding domain. Biochemical characterization of LysB4 enzymatic activity showed that it had optimal peptidoglycan hydrolase activity at pH 8.0-10.0 and 50°C. The lytic activity was dependent on divalent metal ions, especially Zn2+. The antimicrobial spectrum was relatively broad because LysB4 lysed Gram-positive bacteria such as B. cereus, Bacillus subtilis and Listeria monocytogenes and some Gram-negative bacteria when treated with EDTA. LC-MS analysis of the cell wall cleavage products showed that LysB4 was an L-alanoyl-D-glutamate endopeptidase, making LysB4 the first characterized endopeptidase of this type to target B. cereus. LysB4 is believed to be the first reported L-alanoyl-D-glutamate endopeptidase from B. cereus-infecting bacteriophages. The properties of LysB4 showed that this endolysin has strong lytic activity against a broad range of pathogenic bacteria, which makes LysB4 a good candidate as a biocontrol agent against B. cereus and other pathogenic bacteria.

  6. Characterization of LysB4, an endolysin from the Bacillus cereus-infecting bacteriophage B4

    Directory of Open Access Journals (Sweden)

    Son Bokyung

    2012-03-01

    Full Text Available Abstract Background Bacillus cereus is a foodborne pathogen that causes emetic or diarrheal types of food poisoning. The incidence of B. cereus food poisoning has been gradually increasing over the past few years, therefore, biocontrol agents effective against B. cereus need to be developed. Endolysins are phage-encoded bacterial peptidoglycan hydrolases and have received considerable attention as promising antibacterial agents. Results The endolysin from B. cereus phage B4, designated LysB4, was identified and characterized. In silico analysis revealed that this endolysin had the VanY domain at the N terminus as the catalytic domain, and the SH3_5 domain at the C terminus that appears to be the cell wall binding domain. Biochemical characterization of LysB4 enzymatic activity showed that it had optimal peptidoglycan hydrolase activity at pH 8.0-10.0 and 50°C. The lytic activity was dependent on divalent metal ions, especially Zn2+. The antimicrobial spectrum was relatively broad because LysB4 lysed Gram-positive bacteria such as B. cereus, Bacillus subtilis and Listeria monocytogenes and some Gram-negative bacteria when treated with EDTA. LC-MS analysis of the cell wall cleavage products showed that LysB4 was an L-alanoyl-D-glutamate endopeptidase, making LysB4 the first characterized endopeptidase of this type to target B. cereus. Conclusions LysB4 is believed to be the first reported L-alanoyl-D-glutamate endopeptidase from B. cereus-infecting bacteriophages. The properties of LysB4 showed that this endolysin has strong lytic activity against a broad range of pathogenic bacteria, which makes LysB4 a good candidate as a biocontrol agent against B. cereus and other pathogenic bacteria.

  7. Hardness of FeB4: Density functional theory investigation

    Science.gov (United States)

    Zhang, Miao; Lu, Mingchun; Du, Yonghui; Gao, Lili; Lu, Cheng; Liu, Hanyu

    2014-05-01

    A recent experimental study reported the successful synthesis of an orthorhombic FeB4 with a high hardness of 62(5) GPa [H. Gou et al., Phys. Rev. Lett. 111, 157002 (2013)], which has reignited extensive interests on whether transition-metal borides compounds will become superhard materials. However, it is contradicted with some theoretical studies suggesting transition-metal boron compounds are unlikely to become superhard materials. Here, we examined structural and electronic properties of FeB4 using density functional theory. The electronic calculations show the good metallicity and covalent Fe-B bonding. Meanwhile, we extensively investigated stress-strain relations of FeB4 under various tensile and shear loading directions. The calculated weakest tensile and shear stresses are 40 GPa and 25 GPa, respectively. Further simulations (e.g., electron localization function and bond length along the weakest loading direction) on FeB4 show the weak Fe-B bonding is responsible for this low hardness. Moreover, these results are consistent with the value of Vickers hardness (11.7-32.3 GPa) by employing different empirical hardness models and below the superhardness threshold of 40 GPa. Our current results suggest FeB4 is a hard material and unlikely to become superhard (>40 GPa).

  8. EphB4 Regulates Self-Renewal, Proliferation and Neuronal Differentiation of Human Embryonic Neural Stem Cells in Vitro

    Directory of Open Access Journals (Sweden)

    Tingting Liu

    2017-02-01

    Full Text Available Background/Aims: EphB4 belongs to the largest family of Eph receptor tyrosine kinases. It contributes to a variety of pathological progresses of cancer malignancy. However, little is known about its role in neural stem cells (NSCs. This study examined whether EphB4 is required for proliferation and differentiation of human embryonic neural stem cells (hNSCs in vitro. Methods: We up- and down-regulated EphB4 expression in hNSCs using lentiviral over-expression and shRNA knockdown constructs and then investigated the influence of EphB4 on the properties of hNSCs. Results: Our results show that shRNA-mediated EphB4 reduction profoundly impaired hNSCs self-renewal and proliferation. Furthermore, detection of differentiation revealed that knockdown of EphB4 inhibited hNSCs differentiation towards a neuronal lineage and promoted hNSCs differentiation to glial cells. In contrast, EphB4 overexpression promoted hNSCs self-renewal and proliferation, further induced hNSCs differentiation towards a neuronal lineage and inhibited hNSCs differentiation to glial cells. Moreover, we found that EphB4 regulates cell proliferation mediated by the Abl-CyclinD1 pathway. Conclusion: These studies provide strong evidence that fine tuning of EphB4 expression is crucial for the proliferation and neuronal differentiation of hNSCs, suggesting that EphB4 might be an interesting target for overcoming some of the therapeutic limitations of neuronal loss in brain diseases.

  9. Down-Regulation of Neuregulin1/ErbB4 Signaling in the Hippocampus Is Critical for Learning and Memory.

    Science.gov (United States)

    Tian, Jia; Geng, Fei; Gao, Feng; Chen, Yi-Hua; Liu, Ji-Hong; Wu, Jian-Lin; Lan, Yu-Jie; Zeng, Yuan-Ning; Li, Xiao-Wen; Yang, Jian-Ming; Gao, Tian-Ming

    2017-08-01

    Hippocampal function is important for learning and memory, and dysfunction of the hippocampus has been linked to the pathophysiology of neuropsychiatric diseases such as schizophrenia. Neuregulin1 (NRG1) and ErbB4, two susceptibility genes for schizophrenia, reportedly modulate long-term potentiation (LTP) at hippocampal Schaffer collateral (SC)-CA1 synapses. However, little is known regarding the contribution of hippocampal NRG1/ErbB4 signaling to learning and memory function. Here, quantitative real-time PCR and Western blotting were used to assess the mRNA and protein levels of NRG1 and ErbB4. Pharmacological and genetic approaches were used to manipulate NRG1/ErbB4 signaling, following which learning and memory behaviors were evaluated using the Morris water maze, Y-maze test, and the novel object recognition test. Spatial learning was found to reduce hippocampal NRG1 and ErbB4 expression. The blockade of NRG1/ErbB4 signaling in hippocampal CA1, either by neutralizing endogenous NRG1 or inhibiting/ablating ErbB4 receptor activity, enhanced hippocampus-dependent spatial learning, spatial working memory, and novel object recognition memory. Accordingly, administration of exogenous NRG1 impaired those functions. More importantly, the specific ablation of ErbB4 in parvalbumin interneurons also improved learning and memory performance. The manipulation of NRG1/ErbB4 signaling in the present study revealed that NRG1/ErbB4 activity in the hippocampus is critical for learning and memory. These findings might provide novel insights on the pathophysiological mechanisms of schizophrenia and a new target for the treatment of Alzheimer's disease, which is characterized by a progressive decline in cognitive function.

  10. Evaluation of EphA2 and EphB4 as Targets for Image-Guided Colorectal Cancer Surgery.

    Science.gov (United States)

    Stammes, Marieke A; Prevoo, Hendrica A J M; Ter Horst, Meyke C; Groot, Stéphanie A; Van de Velde, Cornelis J H; Chan, Alan B; de Geus-Oei, Lioe-Fee; Kuppen, Peter J K; Vahrmeijer, Alexander L; Pasquale, Elena B; Sier, Cornelis F M

    2017-02-03

    Targeted image-guided oncologic surgery (IGOS) relies on the recognition of cell surface-associated proteins, which should be abundantly present on tumor cells but preferably absent on cells in surrounding healthy tissue. The transmembrane receptor tyrosine kinase EphA2, a member of the A class of the Eph receptor family, has been reported to be highly overexpressed in several tumor types including breast, lung, brain, prostate, and colon cancer and is considered amongst the most promising cell membrane-associated tumor antigens by the NIH. Another member of the Eph receptor family belonging to the B class, EphB4, has also been found to be upregulated in multiple cancer types. In this study, EphA2 and EphB4 are evaluated as targets for IGOS of colorectal cancer by immunohistochemistry (IHC) using a tissue microarray (TMA) consisting of 168 pairs of tumor and normal tissue. The IHC sections were scored for staining intensity and percentage of cells stained. The results show a significantly enhanced staining intensity and more widespread distribution in tumor tissue compared with adjacent normal tissue for EphA2 as well as EphB4. Based on its more consistently higher score in colorectal tumor tissue compared to normal tissue, EphB4 appears to be a promising candidate for IGOS of colorectal cancer. In vitro experiments using antibodies on human colon cancer cells confirmed the possibility of EphB4 as target for imaging.

  11. Neuregulin 1-ErbB4 signaling in the bed nucleus of the stria terminalis regulates anxiety-like behavior.

    Science.gov (United States)

    Geng, Fei; Zhang, Jie; Wu, Jian-Lin; Zou, Wen-Jun; Liang, Zhi-Ping; Bi, Lin-Lin; Liu, Ji-Hong; Kong, Ying; Huang, Chu-Qiang; Li, Xiao-Wen; Yang, Jian-Ming; Gao, Tian-Ming

    2016-08-04

    The bed nucleus of the stria terminalis (BNST), a nucleus defined as part of the extended amygdala, is involved in the expression of anxiety disorders. However, the regulatory mechanisms of BNST inhibitory activity that is involved in anxiety are unknown. Here, we showed that blocking neuregulin 1 (NRG1)-ErbB4 signaling in the BNST of mice, by either neutralizing endogenous NRG1 with ecto-Erbb4 or antagonizing the ErbB4 receptor with its specific inhibitor, produced anxiogenic responses. Interestingly, application of exogenous NRG1 into the BNST induced no anxiolytic effects, suggesting saturating activity of endogenous NRG1. While infusion of the GABAA receptor antagonist bicuculline into the BNST also led to anxiety-related behaviors, it did not worsen the anxiogenic effects produced by blocking NRG1-ErbB4 signaling, suggesting possible involvement of GABAergic neurotransmission. Further, in vitro electrophysiological recordings showed that BNST NRG1-ErbB4 signaling regulated the presynaptic GABA release. Together, these results suggest that NRG1-ErbB4 signaling in the BNST may play an important role in regulating anxiety-like behaviors. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  12. Sintering of B4C by pressureless liquid phase sintering

    International Nuclear Information System (INIS)

    Rocha, Rosa Maria da; Melo, Francisco Cristovao Lourenco de

    2009-01-01

    The effect of three different sintering additive systems on densification of boron carbide powder was investigated. The sintering additives were Al 2 O 3 :Y 2 O 3 , AlN:Y 2 O 3 and BN:Y 2 O 3 compositions. Powder mixtures were prepared with 10 vol% of sintering aids following conventional powder technology processes. Samples were sintered by pressureless sintering at 2050 deg C/30min in argon atmosphere. Sintered samples were compared to a sintered B 4 C without sintering additive. Samples were characterized by XRD to analyze the crystalline phases after sintering and SEM to observe the microstructure and the second phase distribution. YB 4 and YB 2 C 2 were identified in all samples, indicating a reaction between Y 2 O 3 , B 4 C and B 2 O 3 present at the B 4 C particle surface. The best densification result was achieved with Al 2 O 3 :Y 2 O 3 additive system, showing 92.0 % of theoretical density, low porosity and 15.2 % of linear shrinkage. But this sample showed the highest weight loss. (author)

  13. Magnetic anomaly in superconducting TmRh4B4

    International Nuclear Information System (INIS)

    Smith, J.L.; Huang, C.Y.; Tsou, J.J.; Ho, J.C.

    1978-01-01

    The magnetic and superconducting properties of TmRh 4 B 4 (which becomes superconducting at 9.6 K) by means of ac and dc magnetic susceptibility and specific heat measurements are investigated. At 10.7 K, an ac susceptibility peak similar to those found in spin glasses has been observed. In addition, a pronounced specific heat peak has been observed at 11.4 K. The susceptibility peak is essentially unaffected by substitution of 1% Lu or Er for the Tm, but it diminishes when much larger amounts of Er are substituted. The physical origin of this anomalous peak will be discussed

  14. Integral core degradation test with B4C control rod

    International Nuclear Information System (INIS)

    Windberg, P.; Nagy, I.; Matus, L.; Balasko, M.; Hozer, Z.; Czitrovszky, A.; Nagy, A.

    2001-01-01

    The CODEX-B4C VVER bundle test has been successfully performed on 25 th May 2001 in the framework of the COLOSS project of the EU 5 th FWP. The experiment was carried out according to a scenario selected in favour of methane formation. Degradation of control rod and fuel bundle took place at temperatures approx. 2000 oC, cooling down of the bundle was performed in steam atmosphere. The gas composition measurement indicated no methane production during the experiment. The on-line measured data are collected into a database and are available for code validation and development.(author)

  15. HTLV-1 specific CD8+ T cell function augmented by blockade of 2B4/CD48 interaction in HTLV-1 infection.

    Directory of Open Access Journals (Sweden)

    Chibueze Chioma Ezinne

    Full Text Available CD8+ T cell response is important in the response to viral infections; this response though is regulated by inhibitory receptors. Expression of inhibitory receptors has been positively correlated with CD8+ T cell exhaustion; the consequent effect of simultaneous blockade of these inhibitory receptors on CD8+ T cell response in viral infections have been studied, however, the role of individual blockade of receptor-ligand pair is unclear. 2B4/CD48 interaction is involved in CD8+T cell regulation, its signal transducer SAP (signaling lymphocyte activation molecule (SLAM-associated protein is required for stimulatory function of 2B4/CD244 on lymphocytes hence, we analyzed 2B4/CD244 (natural killer cell receptor and SAP (signaling lymphocyte activation molecule(SLAM-associated protein on total CD8+ and HTLV-1 specific CD8+T cells in HTLV-1 infection and the effect of blockade of interaction with ligand CD48 on HTLV-1 specific CD8+ T cell function. We observed a high expression of 2B4/CD244 on CD8+ T cells relative to uninfected and further upregulation on HTLV-1 specific CD8+ T cells. 2B4+ CD8+ T cells exhibited more of an effector and terminally differentiated memory phenotype. Blockade of 2B4/CD48 interaction resulted in improvement in function via perforin expression and degranulation as measured by CD107a surface mobilization on HTLV-1 specific CD8+ T cells. In the light of these findings, we thus propose an inhibitory role for 2B4/CD48 interaction on CD8+T cell function.

  16. Arterial shear stress reduces eph-b4 expression in adult human veins.

    Science.gov (United States)

    Model, Lynn S; Hall, Michael R; Wong, Daniel J; Muto, Akihito; Kondo, Yuka; Ziegler, Kenneth R; Feigel, Amanda; Quint, Clay; Niklason, Laura; Dardik, Alan

    2014-09-01

    Vein graft adaptation to the arterial environment is characterized by loss of venous identity, with reduced Ephrin type-B receptor 4 (Eph-B4) expression but without increased Ephrin-B2 expression. We examined changes of vessel identity of human saphenous veins in a flow circuit in which shear stress could be precisely controlled. Medium circulated at arterial or venous magnitudes of laminar shear stress for 24 hours; histologic, protein, and RNA analyses of vein segments were performed. Vein endothelium remained viable and functional, with platelet endothelial cell adhesion molecule (PECAM)-expressing cells on the luminal surface. Venous Eph-B4 expression diminished (p = .002), Ephrin-B2 expression was not induced (p = .268), and expression of osteopontin (p = .002) was increased with exposure to arterial magnitudes of shear stress. Similar changes were not found in veins placed under venous flow or static conditions. These data show that human saphenous veins remain viable during ex vivo application of shear stress in a bioreactor, without loss of the venous endothelium. Arterial magnitudes of shear stress cause loss of venous identity without gain of arterial identity in human veins perfused ex vivo. Shear stress alone, without immunologic or hormonal influence, is capable of inducing changes in vessel identity and, specifically, loss of venous identity.

  17. Neuregulin repellent signaling via ErbB4 restricts GABAergic interneurons to migratory paths from ganglionic eminence to cortical destinations

    Directory of Open Access Journals (Sweden)

    Li Hao

    2012-02-01

    Full Text Available Abstract Background Cortical GABAergic interneurons (INs are generated in the medial ganglionic eminence (MGE and migrate tangentially into cortex. Because most, if not all, migrating MGE-derived INs express the neuregulin (NRG receptor, ErbB4, we investigated influences of Nrg1 isoforms and Nrg3 on IN migration through ventral telencephalon (vTel and within cortex. Results During IN migration, NRG expression domains and distributions of ErbB4-expressing, MGE-derived INs are complementary with minimal overlap, both in vTel and cortex. In wild-type mice, within fields of NRG expression, these INs are focused at positions of low or absent NRG expression. However, in ErbB4-/- HER4heart mutant mice in which INs lack ErbB4, these complementary patterns are degraded with considerable overlap evident between IN distribution and NRG expression domains. These findings suggest that NRGs are repellents for migrating ErbB4-expressing INs, a function supported by in vitro and in vivo experiments. First, in collagen co-cultures, MGE-derived cells preferentially migrate away from a source of secreted NRGs. Second, cells migrating from wild-type MGE explants on living forebrain slices from wild-type embryonic mice tend to avoid endogenous NRG expression domains, whereas this avoidance behavior is not exhibited by ErbB4-deficient cells migrating from MGE explants and instead they have a radial pattern with a more uniform distribution. Third, ectopic NRG expression in the IN migration pathway produced by in utero electroporation blocks IN migration and results in cortex distal to the blockade being largely devoid of INs. Finally, fewer INs reach cortex in ErbB4 mutants, indicating that NRG-ErbB4 signaling is required for directing IN migration from the MGE to cortex. Conclusions Our results show that NRGs act as repellents for migrating ErbB4-expressing, MGE-derived GABAergic INs and that the patterned expression of NRGs funnels INs as they migrate from the MGE

  18. Clinical Significance of EphB4 and EphB6 Expression in Human Malignant and Benign Thyroid Lesions.

    Science.gov (United States)

    Giaginis, Constantinos; Alexandrou, Paraskevi; Poulaki, Elpida; Delladetsima, Ioanna; Troungos, Constantinos; Patsouris, Efstratios; Theocharis, Stamatios

    2016-04-01

    Ephrin receptors (Ephs) are frequently overexpressed in a wide variety of human malignant tumors, being associated with tumor growth, invasion, angiogenesis and metastasis. The present study aimed to evaluate the clinical significance of EphB4 and EphB6 protein expression in human malignant and benign thyroid lesions. EphB4 and EphB6 protein expression was assessed immunohistochemically on paraffin-embedded thyroid tissues obtained from 127 patients with benign (n = 71) and malignant (n = 56) thyroid lesions. Enhanced EphB4 and EphB6 expression was more frequently observed in malignant compared to benign thyroid lesions (p = 0.0508 and p = 0.0006, respectively). EphB4 and EphB6 expression also provided a distinct discrimination between papillary carcinoma and hyperplastic nodules (p = 0.0302 and p = 0.0013, respectively). In malignant thyroid lesions, enhanced EphB4 expression was significantly associated with larger tumor size (p = 0.0366). Enhanced EphB6 expression was significantly associated with larger tumor size (p = 0.0366), the presence of lymph node metastases (p = 0.0023), the presence of capsular (p = 0.0038), lymphatic (p = 0.0053) and vascular invasion (p = 0.0018) and increased risk of recurrence rate (p = 0.0038). The present study supported evidence that EphB4 and mainly EphB6 may participate in the malignant thyroid transformation, reinforcing their utility as useful biomarkers and possible therapeutic targets in this type of neoplasia.

  19. The glucuronyltransferase B4GAT1 is required for initiation of LARGE-mediated α-dystroglycan functional glycosylation.

    Science.gov (United States)

    Willer, Tobias; Inamori, Kei-Ichiro; Venzke, David; Harvey, Corinne; Morgensen, Greg; Hara, Yuji; Beltrán Valero de Bernabé, Daniel; Yu, Liping; Wright, Kevin M; Campbell, Kevin P

    2014-10-03

    Dystroglycan is a cell membrane receptor that organizes the basement membrane by binding ligands in the extracellular matrix. Proper glycosylation of the α-dystroglycan (α-DG) subunit is essential for these activities, and lack thereof results in neuromuscular disease. Currently, neither the glycan synthesis pathway nor the roles of many known or putative glycosyltransferases that are essential for this process are well understood. Here we show that FKRP, FKTN, TMEM5 and B4GAT1 (formerly known as B3GNT1) localize to the Golgi and contribute to the O-mannosyl post-phosphorylation modification of α-DG. Moreover, we assigned B4GAT1 a function as a xylose β1,4-glucuronyltransferase. Nuclear magnetic resonance studies confirmed that a glucuronic acid β1,4-xylose disaccharide synthesized by B4GAT1 acts as an acceptor primer that can be elongated by LARGE with the ligand-binding heteropolysaccharide. Our findings greatly broaden the understanding of α-DG glycosylation and provide mechanistic insight into why mutations in B4GAT1 disrupt dystroglycan function and cause disease.

  20. receptores

    Directory of Open Access Journals (Sweden)

    Salete Regina Daronco Benetti

    2006-01-01

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

  1. EphB4 Tyrosine Kinase Stimulation Inhibits Growth of MDA-MB-231 Breast Cancer Cells in a Dose and Time Dependent Manner

    Directory of Open Access Journals (Sweden)

    Farnaz Barneh

    2013-01-01

    Full Text Available Background. EphB4 receptor tyrosine kinase is of diagnostic and therapeutic value due to its overexpression in breast tumors. Dual functions of tumor promotion and suppression have been reported for this receptor based on presence or absence of its ligand. To elucidate such discrepancy, we aimed to determine the effect of time- and dose-dependent stimulation of EphB4 on viability and invasion of breast cancer cells via recombinant ephrinB2-Fc. Methods. Cells were seeded into multiwell plates and were stimulated by various concentrations of preclustered ephrinB2-Fc. Cell viability was measured on days 3 and 6 following treatment using alamar-blue when cells were in different states of confluence. Results. Stimulation of cells with ephrinB2 did not pose any significant effect on cell viability before reaching confluence, while inhibition of cell growth was detected after 6 days when cells were in postconfluent state following a dose-dependent manner. EphrinB2 treatment did not affect tubular formation and invasion on matrigel. Conclusion. This study showed that EphB4 can differentially inhibit cells at post confluent state and that presence of ligand manifests growth-inhibitory properties of EphB4 receptor. It is concluded that growth inhibition has occurred possibly due to long treatment with ligand, a process which leads to receptor downregulation.

  2. 26 CFR 1.475(b)-4 - Exemptions-transitional issues.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 6 2010-04-01 2010-04-01 false Exemptions-transitional issues. 1.475(b)-4 Section 1.475(b)-4 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Inventories § 1.475(b)-4 Exemptions—transitional issues. (a...

  3. 26 CFR 1.1092(b)-4T - Mixed straddles; mixed straddle account (temporary).

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 11 2010-04-01 2010-04-01 true Mixed straddles; mixed straddle account (temporary). 1.1092(b)-4T Section 1.1092(b)-4T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Wash Sales of Stock Or Securities § 1.1092(b)-4T...

  4. The effect of hydrogen on B4C coatings fabrication in inductively coupled plasma torch

    Directory of Open Access Journals (Sweden)

    Q. J. Guo

    2018-02-01

    Full Text Available Boron carbide (B4C coatings are prepared by an RF inductively coupled plasma (ICP torch with different amounts of hydrogen introduced into the sheath gas. The effects of the added hydrogen on the characteristics of the plasma are diagnosed by optical emission spectroscopy and high speed photography. The effects on the melting of B4C particles in the plasma are studied by scanning electron microscopy (SEM. The microstructure of the B4C coatings was determined with SEM imaging and x-ray diffraction analysis. The results show that adding hydrogen to the sheath gas leads to plasma contraction, which results in higher gas temperature of plasma. It also enhances B4C particles spheroidizing and improves the compactness of B4C coatings. Plasma processing does not change the main phase of boron carbide. The obtained results on B4C coatings on Cu substrates allows for improving the B4C coatings fabrication process.

  5. Microstructure Analysis of Neutron Absorber Al/B4C Metal Matrix Composites

    Directory of Open Access Journals (Sweden)

    Jianxin Lin

    2017-12-01

    Full Text Available The microstructure of Al/B4C metal matrix composites (MMCs used as neutron absorbers in both dry storage casks and wet storage pools of spent nuclear fuel was analyzed by SEM and TEM. A polishing method of a focused Ga+ ion beam was used to obtain an ideal sample surface with very low roughness, which was used to statistically analyze the distribution characteristics and size factor of B4C particles in the aluminum matrix. The area of B4C particles mainly ranged from 0 to 0.5 μm2, which was the proportion of 64.29%, 86.99% and 76.86% of total statistical results for the Al-15%B4C, Al-25%B4C and Al-30%B4C MMCs, respectively. The average area of B4C particles in the Al-15%B4C, Al-25%B4C and Al-30%B4C MMCs were about 1.396, 0.528 and 1.183 μm2, respectively. The nanoscale precipitates were analyzed by the element mappings in scanning transmission electron microscopy (STEM mode and electron energy loss spectroscopy (EELS mode, which included elliptic alloy precipitates with elemental Cu, Cr, Fe and Si, except for Al, and B4C nanoparticles with polygonal shape. The interface characteristics showed that the (021 crystal plane of B4C particle and (111 crystal plane of aluminum matrix grew together. The lattice misfit was about 1.68% for (111Al//(021B4C. The corrosion properties and corresponding mechanism of Al/B4C MMCs were investigated in an aqueous solution with 5000 ppm boric acid at 100 °C and atmospheric pressure, which showed that the mass increment rate was first decreased with increasing corrosion time and then increased.

  6. Nuclear ErbB4 signaling through H3K9me3 is antagonized by EGFR-activated c-Src.

    Science.gov (United States)

    Ishibashi, Kenichi; Fukumoto, Yasunori; Hasegawa, Hitomi; Abe, Kohei; Kubota, Shoichi; Aoyama, Kazumasa; Kubota, Sho; Nakayama, Yuji; Yamaguchi, Naoto

    2013-01-15

    The ErbB family of receptor tyrosine kinases comprises four members: epidermal growth factor receptor (EGFR)/ErbB1, HER2/ErbB2, ErbB3 and ErbB4, and plays roles in signal transduction at the plasma membrane upon ligand stimulation. Stimulation with neuregulin-1 (NRG-1) cleaves ErbB4 and releases the ErbB4 intracellular domain (4ICD) that translocates into the nucleus to control gene expression. However, little is known about the regulation of 4ICD nuclear signaling through tyrosine phosphorylation. We show here that 4ICD nuclear signaling is antagonized by EGF-induced c-Src activation through EGFR. Generation of 4ICD by NRG-1 leads to increased levels of trimethylated histone H3 on lysine 9 (H3K9me3) in a manner dependent on the nuclear accumulation of 4ICD and its tyrosine kinase activity. Once EGF activates c-Src downstream of EGFR concomitantly with NRG-1-induced ErbB4 activation, c-Src associates with phospho-Tyr950 and phospho-Tyr1056 on 4ICD, thereby decreasing nuclear accumulation of 4ICD and inhibiting an increase of H3K9me3 levels. Moreover, 4ICD-induced transcriptional repression of the human telomerase reverse transcriptase (hTERT) is inhibited by EGF-EGFR-Src signaling. Thus, our findings reveal c-Src-mediated inhibitory regulation of ErbB4 nuclear signaling upon EGFR activation.

  7. B4G local area: high level requirements and system design

    DEFF Research Database (Denmark)

    Mogensen, Preben; Pajukoski, Kari; Raaf, Bernhard

    2012-01-01

    A next generation Beyond 4G (B4G) radio access technology is expected to become available around 2020 in order to cope with the exponential increase of mobile data traffic. In this paper, research motivations and high level requirements for a B4G local area concept are discussed. Our suggestions...... on the design of the B4G system as well as on the choice of its key technology components are also presented....

  8. First-principles calculation of the indentation strength of FeB4

    Science.gov (United States)

    Li, Bing; Sun, Hong; Chen, Changfeng

    2014-07-01

    A recent experiment [H. Y. Gou et al., Phys. Rev. Lett. 111, 157002 (2013), 10.1103/PhysRevLett.111.157002] reported a measured Vickers hardness of over 60 GPa for FeB4, placing it as a superhard material far above all other similar ultrahard transition-metal borides, such as ReB2,WB4, and especially CrB4, which has the same crystalline structure as that of FeB4 but a much lower measured Vickers hardness of around 23 GPa. This result, however, is contradicted by theoretical calculations that predict a smaller shear modulus for FeB4 than that of CrB4, indicating that FeB4 is softer than CrB4. Here we report first-principles calculations that aim to understand the stress response of FeB4 under indentation loadings and examine whether there exists a strain-stiffening effect that might enhance the indentation strength. Our results show that there is no strain stiffening in FeB4; instead, the normal pressure beneath the indenter drives a lateral structural expansion which further stretches and weakens the boron-boron and boron-iron bonds in addition to that caused by the shear deformation in Vickers indentation tests. This effect leads to a considerably reduced strength of FeB4, producing an ideal (i.e., an upper bound) indentation strength of 17 GPa that is lower than that (27 GPa) predicted for CrB4. The present results suggest that FeB4 is unlikely to be superhard and further experimental investigation is needed to clarify this issue.

  9. 29 CFR 2530.200b-4 - One-year break in service.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false One-year break in service. 2530.200b-4 Section 2530.200b-4... General Provisions § 2530.200b-4 One-year break in service. (a) Computation period. (1) Under sections 202... that an employee incurs a one-year break in service for a computation period or periods if the employee...

  10. PARTICLE SIZE-DEPENDENT PULVERIZATION OF B4C AND GENERATION OF B4C/STS NANOPARTICLES USED FOR NEUTRON ABSORBING COMPOSITES

    Directory of Open Access Journals (Sweden)

    JAEWOO KIM

    2014-10-01

    Full Text Available Pulverization of two different sized micro-B4C particles (∼10 μm and ∼150 μm was investigated using a STS based high energy ball milling system. Shapes, generation of the impurities, and reduction of the particle size dependent on milling time and initial particle size were investigated using various analytic tools including SEM-EDX, XRD, and ICP-MS. Most of impurity was produced during the early stage of milling, and impurity content became independent on the milling time after the saturation. The degree of particle size reduction was also dependent on the initial B4C size. It was found that the STS nanoparticles produced from milling is strongly bounded with the B4C particles forming the B4C/STS composite particles that can be used as a neutron absorbing nanocomposite. Based on the morphological evolution of the milled particles, a schematic pulverization model for the B4C particles was constructed.

  11. Heat release from B4C oxidation in steam and air

    International Nuclear Information System (INIS)

    Belovsky, L.

    1996-01-01

    BWR and some PWR cores contain boron carbide (B 4 C) as neutron absorber. During a severe accident, the B 4 C can potentially react with steam under release of heat and hydrogen. Although models for B 4 C oxidation already exist in MELCOR and SCDAP/RELAP5, a development of a new model for another computer code seems to be difficult due to a missing comprehensive description of the current modelling methodology and scarce experimental data. The aim of this paper is to highlight the key points of the B 4 C oxidation using the existing available experimental data and to perform a simple heat balance analysis of the B 4 C/steam and B 4 C/air chemical reactions. The analysis of literature data shows that the B 4 C oxidation phenomenon is qualitatively well described below 1000 deg. C. However, no reliable data exist for the reaction kinetics especially above this temperature. It was found that the experimental results strongly depend on the experimental arrangement. The reaction heats, calculated in this study, indicate that the B 4 C oxidation is an exothermic reaction, releasing more heat in air than in steam. The formation of boric acids from the boron oxide increases the heat release from B 4 C by ∼ 10%, in the worst case. Although the total heat, released in a PWR core from the B 4 C oxidation, is probably much smaller than the heat released from the Zr/steam reaction, it is not excluded that the B 4 C oxidation can locally contribute to the damage of the control elements due to local overheating. Modelling of these phenomena is, however, very difficult due to the complex geometry of the liquefied control elements and due to absence of suitable data on the reaction kinetics. (author). 25 refs, 2 figs, 3 tabs

  12. NLRP3 Inflammasome Deficiency Protects against Microbial Sepsis via Increased Lipoxin B4 Synthesis.

    Science.gov (United States)

    Lee, Seonmin; Nakahira, Kiichi; Dalli, Jesmond; Siempos, Ilias I; Norris, Paul C; Colas, Romain A; Moon, Jong-Seok; Shinohara, Masakazu; Hisata, Shu; Howrylak, Judie Ann; Suh, Gee-Young; Ryter, Stefan W; Serhan, Charles N; Choi, Augustine M K

    2017-09-15

    Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection, is a major public health concern with high mortality and morbidity. Although inflammatory responses triggered by infection are crucial for host defense against invading microbes, the excessive inflammation often causes tissue damage leading to organ dysfunction. Resolution of inflammation, an active immune process mediated by endogenous lipid mediators (LMs), is important to maintain host homeostasis. We sought to determine the role of the nucleotide-binding domain, leucine-rich repeat-containing receptor, pyrin domain-containing-3 (NLRP3) inflammasome in polymicrobial sepsis and regulation of LM biosynthesis. We performed cecal ligation and puncture (CLP) using mice lacking NLRP3 inflammasome-associated molecules to assess mortality. Inflammation was evaluated by using biologic fluids including plasma, bronchoalveolar, and peritoneal lavage fluid. Local acting LMs in peritoneal lavage fluid from polymicrobacterial septic mice were assessed by mass spectrometry-based metabololipidomics. Genetic deficiency of NLRP3 inhibited inflammatory responses and enhanced survival of CLP-induced septic mice. NLRP3 deficiency reduced proinflammatory LMs and increased proresolving LM, lipoxin B 4 (LXB 4 ) in septic mice, and in macrophages stimulated with LPS and ATP. Activation of the NLRP3 inflammasome induced caspase-7 cleavage and pyroptosis. Caspase-7 deficiency similarly reduced inflammation and mortality in CLP-induced sepsis, and increased LXB 4 production in vivo and in vitro. Exogenous application of LXB 4 reduced inflammation, pyroptosis, and mortality of mice after CLP. Genetic deficiency of NLRP3 promoted resolution of inflammation in polymicrobial sepsis by relieving caspase-7-dependent repression of LXB 4 biosynthesis, and increased survival potentially via LXB 4 production and inhibition of proinflammatory cytokines.

  13. Leukotriene B4 Enhances NOD2-Dependent Innate Response against Influenza Virus Infection.

    Directory of Open Access Journals (Sweden)

    Manon Le Bel

    Full Text Available Leukotriene B4 (LTB4, a central mediator of inflammation, is well known for its chemoattractant properties on effectors cells of the immune system. LTB4 also has the ability to control microbial infection by improving host innate defenses through the release of antimicrobial peptides and modulation of intracellular Toll-like receptors (TLRs expression in response to agonist challenge. In this report, we provide evidences that LTB4 acts on nucleotide-binging oligomerization domain 2 (NOD2 pathway to enhance immune response against influenza A infection. Infected mice receiving LTB4 show improved survival, lung architecture and reduced lung viral loads as compared to placebo-treated animals. NOD2 and its downstream adaptor protein IPS-1 have been found to be essential for LTB4-mediated effects against IAV infection, as absence of NOD2 or IPS-1 diminished its capacity to control viral infection. Treatment of IAV-infected mice with LTB4 induces an increased activation of IPS-1-IRF3 axis leading to an enhanced production of IFNβ in lungs of infected mice. LTB4 also has the ability to act on the RICK-NF-κB axis since administration of LTB4 to mice challenged with MDP markedly increases the secretion of IL-6 and TNFα in lungs of mice. TAK1 appears to be essential to the action of LTB4 on NOD2 pathway since pretreatment of MEFs with TAK1 inhibitor prior stimulation with IAV or MDP strongly abrogated the potentiating effects of LTB4 on both IFNβ and cytokine secretion. Together, our results demonstrate that LTB4, through its ability to activate TAK1, potentiates both IPS-1 and RICK axis of the NOD2 pathway to improve host innate responses.

  14. 2B4 expression on natural killer cells increases in HIV-1 infected patients followed prospectively during highly active antiretroviral therapy

    DEFF Research Database (Denmark)

    Ostrowski, S R; Ullum, H; Pedersen, Bente Klarlund

    2005-01-01

    by highly active antiretroviral therapy (HAART), low-level viraemia, proviral-DNA or immune activation in HIV-1 infected patients. A total of 101 HAART-treated HIV-1 infected patients with HIV-RNA copies/ml were followed prospectively for 24 months. HIV-RNA was investigated 3-monthly and 2B4...... expression on CD3- CD16+ NK cells and CD3+ CD8+ cells, proviral-DNA and plasma soluble tumour necrosis factor receptor (sTNFr)-II were investigated 6-monthly. For comparison, 2B4 expression was investigated in 20 healthy individuals. The concentration of 2B4+ NK cells was initially reduced in HIV-1 infected...... follow-up (both P DNA carrying cells and plasma sTNFrII were associated with reductions in the concentration of 2B4+ NK cells (all P HIV-RNA had no effect on 2B4 expression on NK cells or CD3+ CD8+ cells. These findings demonstrate that the concentration of 2B...

  15. TGF-β1 down-regulation of NKG2D/DAP10 and 2B4/SAP expression on human NK cells contributes to HBV persistence.

    Directory of Open Access Journals (Sweden)

    Cheng Sun

    Full Text Available The mechanism underlying persistent hepatitis B virus (HBV infection remains unclear. We investigated the role of innate immune responses to persistent HBV infection in 154 HBV-infected patients and 95 healthy controls. The expression of NKG2D- and 2B4-activating receptors on NK cells was significantly decreased, and moreover, the expression of DAP10 and SAP, the intracellular adaptor proteins of NKG2D and 2B4 (respectively, were lower, which then impaired NK cell-mediated cytotoxic capacity and interferon-γ production. Higher concentrations of transforming growth factor-beta 1 (TGF-β1 were found in sera from persistently infected HBV patients. TGF-β1 down-regulated the expression of NKG2D and 2B4 on NK cells in our in vitro study, leading to an impairment of their effector functions. Anti-TGF-β1 antibodies could restore the expression of NKG2D and 2B4 on NK cells in vitro. Furthermore, TGF-β1 induced cell-cycle arrest in NK cells by up-regulating the expression of p15 and p21 in NK cells from immunotolerant (IT patients. We conclude that TGF-β1 may reduce the expression of NKG2D/DAP10 and 2B4/SAP, and those IT patients who are deficient in these double-activating signals have impaired NK cell function, which is correlated with persistent HBV infection.

  16. Exoelectron emission from surface layer of Li2B4O7 glass ceramics

    International Nuclear Information System (INIS)

    Kawamoto, Takamichi; Katsube, Shizuko; Yanagisawa, Hideo; Kikuchi, Riichi; Kawanishi, Masaharu.

    1984-01-01

    The thermally stimulated exoelectron emission (TESS) of Li 2 B 4 O 7 glass ceramics was investigated for its application to the dosimetric use. It has been found the TSEE glow patterns of Li 2 B 4 O 7 glass ceramics and of the thin layer of LiF evaporated on Li 2 B 4 O 7 glass ceramics depend on the kind of radiations irradiated. The TSEE glow pattern of the duplicated structure sample indicated a possibility of determining the dose of each kind of radiation separately in the mixed radiation field. (author)

  17. Release of adenosine from human neutrophils stimulated by platelet activating factor, leukotriene B4 and opsonized zymosan

    Directory of Open Access Journals (Sweden)

    S. Sipka

    1992-01-01

    Full Text Available Isolated human polymorphonuclear leukocytes (PMNL stimulated by platelet activating factor (PAF, leukotriene B4 (LTB4 or opsonized zymosan (OZ released adenosine measured by thermospray high performance liquid chromatography mass spectrometry in the cell-free supernatants. Stimulation by PAF or LTB4 resulted in a bellshaped concentration-effect curve; 5 × 10−7 M PAF, 10−8 M LTB4 and 500 μg ml−1 OZ induced peak adenosine release, thus cytotoxic concentrations did not elevate adenosine level in the supernatants. Therefore adenosine release was characteristic of viable cells. As calculated from concentration-effect curves, the rank order of potency for adenosine release was PAF > LTB > OZ. These resuits suggest that adenosine, when bound specifically to membrane receptor sites, may initiate signal transduction, and, in co-operation with other inflammatory mediators, may modulate phagocyte function, e.g. production of chemoluminescence (CL.

  18. Origin of modulated phases and magnetic hysteresis in TmB4

    Science.gov (United States)

    Wierschem, Keola; Sunku, Sai Swaroop; Kong, Tai; Ito, Toshimitsu; Canfield, Paul C.; Panagopoulos, Christos; Sengupta, Pinaki

    2015-12-01

    We investigate the low-temperature magnetic phases in TmB4 , a metallic quantum magnet on the geometrically frustrated Shastry-Sutherland lattice, using coordinated experimental and theoretical studies. Our results provide an explanation for the appearance of the intriguing fractional plateau in TmB4 and accompanying magnetic hysteresis. Together with observation of the bump in the half plateau, our results support the picture that the magnetization plateau structure in TmB4 is strongly influenced by the zero-field modulated phases. We present a phenomenological model to explain the appearance of the modulated phases and a microscopic Hamiltonian that captures the complete magnetic behavior of TmB4 .

  19. Study of influence content of TiB2 by reaction in situ B4C and TiC in mechanical properties on B4C ceramics

    International Nuclear Information System (INIS)

    Coelho, M.L. Ramos; Bressiani, J.C.; Gomide, R.G.; Andrade, F.A. de

    2012-01-01

    The low density of ceramic materials promoted a change in research lines in the defense field. Research efforts and development directed to obtaining products of high density sintered of Al2O3, SiC and B4C, using different routes, both traditional as innovative, led to promising initial results, which justify the convergence of skills for the consolidation of research lines and the nationalization that sintered components of B4C with characteristics and properties compatible with the technical requirements established for the ballistic application. The low density of boron carbide (2.52 g/cm 3 ) gives in the final product a weight approximately 30% lower than armor made of alumina (3.96 g/cm 3 ). (author)

  20. The mean grain size determination of boron carbide (B4C)-aluminium (Al) and boron carbide (B4C)-nickel (Ni) composites by ultrasonic velocity technique

    International Nuclear Information System (INIS)

    Unal, Ridvan; Sarpuen, Ismail H.; Yalim, H. Ali; Erol, Ayhan; Ozdemir, Tuba; Tuncel, Sabri

    2006-01-01

    In this study, the mean grain size of ceramic-metal composites, made from boron carbide (B 4 C)-aluminium (Al)-nickel (Ni) powders, has been determined with ultrasonic velocity technique by using a 2 MHz transducer. An ultrasonic velocity-grain size master graph was plotted using a 4 MHz ultrasonic transducer. The results were compared to the mean grain size obtained from SEM (Scanning Electron Microscopy) images

  1. Kondo hybridization and quantum criticality in β -YbAlB4 by laser ARPES

    Science.gov (United States)

    Bareille, Cédric; Suzuki, Shintaro; Nakayama, Mitsuhiro; Kuroda, Kenta; Nevidomskyy, Andriy H.; Matsumoto, Yosuke; Nakatsuji, Satoru; Kondo, Takeshi; Shin, Shik

    2018-01-01

    We report an angle-resolved photoemission (ARPES) study of β -YbAlB4 , which is known to harbor unconventional quantum criticality (QC) without any tuning. We directly observe a quasiparticle peak (QP) emerging from hybridization, characterized by a binding energy and an onset of coherence both at about 4 meV. This value conforms with a previously observed reduced Kondo scale at about 40 K. Consistency with an earlier study of carriers in β -YbAlB4 via the Hall effect strongly suggests that this QP is responsible for the QC in β -YbAlB4 . A comparison with the sister polymorph α -YbAlB4 , which is not quantum critical at ambient pressure, further supports this result. Indeed, within the limitation of our instrumental resolution, our ARPES measurements do not show tangible sign of hybridization in this locally isomorphic system, while the conduction band we observe is essentially the same as in β -YbAlB4 . We therefore claim that we identified by ARPES the carriers responsible for the QC in β -YbAlB4 . The observed dispersion and the underlying hybridization of this QP are discussed in the context of existing theoretical models.

  2. Enhanced tensile strength and thermal conductivity in copper diamond composites with B4C coating.

    Science.gov (United States)

    Sun, Youhong; He, Linkai; Zhang, Chi; Meng, Qingnan; Liu, Baochang; Gao, Ke; Wen, Mao; Zheng, Weitao

    2017-09-06

    Boron carbide (B 4 C) coating on diamond particle is synthesized by heating diamond particles in a powder mix of H 3 BO 3 and B in Ar atmosphere. The composition, bond state and coverage fraction of boron carbide coating on diamond particles are investigated. The boron carbide coating favors to grow on diamond (100) surface rather than on diamond (111) surface. Cu matrix composites reinforced with B 4 C-coated diamond particles were made by powder metallurgy. The addition of B 4 C coating gave rise to a dense composite. The influence of B 4 C coating on both tensile strength and thermal conductivity of the composite were investigated. When the B 4 C fully covered on diamond particles, the composite exhibited a greatly increase in tensile strength (115 MPa) which was much higher than that for uncoated-diamond/Cu (60 MPa) composites. Meanwhile, a high thermal conductivity of 687 W/mK was achieved in the B 4 C-coated-diamond/Cu composites.

  3. Investigation of addition of B 4C particles coated by nano-TiB II on microstructure and mechanical behavior of Al-B 4C composites

    Science.gov (United States)

    Abdizadeh, H.; Baharvandi, H. R.; Jebelli, F. B.; Ehsani, N.

    2007-07-01

    In this research, a casting system was designed for manufacturing Al-B 4C composites in 5, 10 and 15 vol.%B 4C, while two types of particles (non coated and coated with nano-TiB II by sol-gel method) were added at 800 and 1000°C. The resulting composites were tested for their mechanical properties and microstructure to study the effect of coating and temperature parameters. Mechanical properties such as tensile strength and hardness were higher in the case of coated particles in 1000°C, compared to the similar samples in 800°C and also the composites with non coated particles. It is also observed that these properties improve with increasing the fraction of particles (up to 10 vol.%). X-ray diffraction studies also confirmed the effective role of coating in appearing of boron carbide peak in diffraction patterns. Additionally, the distribution of B 4C particles in the matrix is found to be more uniform in samples with coated particles. The wetability of particles with molten alloy was also improved. In general, the results show that manufacturing these composites by vortex method in case of using non coated boron carbide powders is not successful, while coating with nano-TiB II and increasing casting temperature can improve the wetability and consequently the incorporation of particles.

  4. Interface characterization of B4C-based multilayers by X-ray grazing-incidence reflectivity and diffuse scattering.

    Science.gov (United States)

    Jiang, Hui; Wang, Zhanshan; Zhu, Jingtao

    2013-05-01

    B4C-based multilayers have important applications for soft to hard X-rays. In this paper, X-ray grazing-incidence reflectivity and diffuse scattering, combining various analysis methods, were used to characterize the structure of B4C-based multilayers including layer thickness, density, interfacial roughness, interdiffusion, correlation length, etc. Quantitative results for W/B4C, Mo/B4C and La/B4C multilayers were compared. W/B4C multilayers show the sharpest interfaces and most stable structures. The roughness replications of La/B4C and Mo/B4C multilayers are not strong, and oxidations and structure expansions are found in the aging process. This work provides guidance for future fabrication and characterization of B4C-based multilayers.

  5. Wetting of B4C, TiC and graphite substrates by molten Mg

    International Nuclear Information System (INIS)

    Zhang Dan; Shen Ping; Shi Laixin; Jiang Qichuan

    2011-01-01

    Highlights: → The wettability of TiC, B4C and C by molten Mg was determined using an improved sessile drop method. → A new method to evaluate the wetting behavior coupled with evaporation and reaction was proposed. → The bonding characteristics in the Mg/B4C, Mg/TiC and Mg/graphite systems were evaluated. - Abstract: The isotherm wetting of B 4 C, TiC and graphite substrates by molten Mg was studied in a flowing Ar atmosphere at 973-1173 K using an improved sessile drop method. The initial contact angles are in the ranges of 95-87 deg., 74-60 deg. and 142-124 deg., respectively, moderately depending on the temperature. All the systems are non-reactive in nature; however, the presence of impurity of free boron at the B 4 C surface gave rise to the chemical reaction with molten Mg and thus promoted the wettability to a certain degree. A new method was proposed to evaluate the wetting behavior coupled with evaporation and chemical reaction. Furthermore, based on the comparison of the work of adhesion and cohesion, the bonding in the Mg/B 4 C and Mg/TiC systems is presumably mainly chemical while that in the Mg/graphite system is physical.

  6. B4C-MODIFIED SiO2-PHENOLIC Composites for Enhanced Ablation Resistance

    Science.gov (United States)

    Li, Maoyuan; Lu, Lin; Dai, Zhen; Hong, Yiqiang; Chen, Weiwei; Zhang, Yuping; Qiao, Yingjie

    In the present paper, the silica-phenolic composite (S-Ph) composites with different amount of B4C were prepared, and the ablation tests of these composites were carried out using oxygen-acetylene jet. The ablation process was systematically investigated. The addition of B4C with appropriate amount can efficiently improve the ablation resistance of S-Ph. The results showed that S-Ph containing B4C powder of 2wt.% exhibited the lowest linear and mass ablation rate. The influence mechanism for the results was analyzed deeply. The surface morphologies, phase composition, density and thermal conductivity of composites were characterized using a scanning electron microscope (SEM), X-Ray Diffraction (XRD), Archimedes method, and thermal conductivity meter, respectively. The present investigation will provide a theoretical basis for the preparation of the ablation resistant material.

  7. Radiation defects in SrB4O7:Eu2+ crystals

    International Nuclear Information System (INIS)

    Yavetskiy, R.P.; Dolzhenkova, E.F.; Tolmachev, A.V.; Parkhomenko, S.V.; Baumer, V.N.; Prosvirnin, A.L.

    2007-01-01

    Radiation-induced defects in SrB 4 O 7 :Eu 2+ (0.033 at.%) single crystal irradiated with γ and X-ray quanta has been studied. The induced optical absorption in the 400-700 nm region has been ascribed to F + centers. The Eu 2+ ions have been shown to act simultaneously as traps and as radiative recombination centers of charge carriers. Basing on the thermally stimulated luminescence (TSL), optical absorption and photoluminescence studies of SrB 4 O 7 :Eu 2+ crystals, a TSL mechanism has been proposed associated with the decay of F + centers being in non-equivalent crystallographic positions followed by radiative recombination of charge carriers on europium ions. Various positions of localization of the radiation-induced defects in the SrB 4 O 7 crystal structure have been discussed

  8. ErbB4 in laminated brain structures: a neurodevelopmental approach to schizophrenia

    Directory of Open Access Journals (Sweden)

    Carlos Gustavo Perez-Garcia

    2015-12-01

    Full Text Available The susceptibility genes for schizophrenia Neuregulin-1 (NRG1 and ErbB4 have critical functions during brain development and in the adult. Alterations in the ErbB4 signaling pathway cause a variety of neurodevelopmental defects including deficiencies in neuronal migration, synaptic plasticity and myelination. I have used the ErbB4-/- HER4heart KO mice to study the neurodevelopmental insults associated to deficiencies in the NRG1-ErbB4 signaling pathway and their potential implication with brain disorders such as schizophrenia, a chronic psychiatric disease affecting 1% of the population worldwide. ErbB4 deletion results in an array of neurodevelopmental deficits that are consistent with a schizophrenic model. First, similar defects appear in multiple brain structures, from the cortex to the cerebellum. Second, these defects affect multiple aspects of brain development, from deficits in neuronal migration to impairments in excitatory/inhibitory systems, including reductions in brain volume, cortical and cerebellar heteropias, alterations in number and distribution of specific subpopulations of interneurons, deficiencies in the astrocytic and oligodendrocytic lineages, and additional insults in major brain structures. This suggests that alterations in specific neurodevelopmental genes that play similar functions in multiple neuroanatomical structures might account for some of the symptomatology observed in schizophrenic patients, such as defects in cognition. ErbB4 mutation uncovers flaws in brain development that are compatible with a neurodevelopmental model of schizophrenia, and it establishes a comprehensive model to study the basis of the disorder before symptoms are detected in the adult.

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

    DEFF Research Database (Denmark)

    Skaanderup, Philip Robert; Madsen, Robert

    2001-01-01

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

  10. Application of full factorial design to study the tribological properties of AA6061-B4C and AA6061-B4C-MoS2 composites

    Directory of Open Access Journals (Sweden)

    Monikandan V. V.

    2018-03-01

    Full Text Available This study statistically analyzes the tribological properties of AA6061-10 wt. % B4C mono composite and AA6061-10 wt.% B4C-7.5 wt. % MoS2 hybrid composite. The tribological behavior of the composites was studied at atmospheric conditions using a pin-on-disk tribo-tester. The tribological experiments were conducted as per the full factorial design (FFD experimental scheme. The ANOVA analysis of the wear rate revealed that the three factors, A (MoS2 particles addition, B (applied load, and D (sliding distance presented the physical and statistical significance on the wear rate. The ANOVA analysis of the friction coefficient revealed that the factors B (applied load and C (sliding speed and interaction AB (interaction of MoS2 particles addition and applied load presented the physical and statistical significance on the friction coefficient. It is observed from the main effects plots of the wear rate and friction coefficient that the increase in the levels of factors B (applied load and D (sliding distance increased the wear rate and friction coefficient. However, the wear rate and friction coefficient decreased with the increase in the level of factor A (MoS2 particles addition.

  11. Tricritical behavior in the ferromagnetic superconductor ErRh4B4

    International Nuclear Information System (INIS)

    Crabtree, G.W.; Kalia, R.K.; Hinks, D.G.; Behroozi, F.; Tachiki, M.

    1985-08-01

    A new tricritical point on the phase boundary between the superconducting vortex phase and the normal paramagnetic phase of ErRh 4 B 4 is presented. The microscopic origin of the tricritical point and the expected tricritical behavior are briefly discussed

  12. Coxeter groups A4, B4 and D4 for two-qubit systems

    Indian Academy of Sciences (India)

    physics pp. 247–260. Coxeter groups A4, B4 and D4 for two-qubit systems. RAMAZAN KOÇ1,∗. , M YAKUP HACIIBRAHIMO ˇGLU1 and MEHMET KOCA2 ... reflection matrices. The von Neumann entropy of each reduced density matrix is calculated. It is shown that these unitary matrix representations are naturally related to ...

  13. Effect of secondary phases on the properties of B4C-Al composites

    International Nuclear Information System (INIS)

    Sarikaya, M.; Pysik, A.J.; Ilsay, I.A.; Snowden, W.E.

    1985-01-01

    Various secondary phases form during the processing of B 4 C-Al composites depending on the processing variables. The type and distribution of these phases are indicated by the reactions which take place during the densification process. Microstructures of the samples prepared under different processing conditions are investigated and correlated with the mechanical properties

  14. TEM characterization of La/B4C multilayer systems by the geometric phase method

    NARCIS (Netherlands)

    Häussler, D.; Spiecker, E.; Yang, S.; Jäger, W.; Störmer, M.; Bormann, R.; Zwicker, G.

    2005-01-01

    New La/B4C multilayer systems with layer thicknesses in the nanometer range have been deposited onto structured silicon (001) surfaces by magnetron sputtering and have been characterized by transmission electron microscopy (TEM). By applying a geometric phase method which has been originally

  15. On the Potential of Interference Rejection Combining in B4G Networks

    DEFF Research Database (Denmark)

    Tavares, Fernando Menezes Leitão; Berardinelli, Gilberto; Mahmood, Nurul Huda

    2013-01-01

    Beyond 4th Generation (B4G) local area networks will be characterized by the dense uncoordinated deployment of small cells. This paper shows that inter-cell interference, which is a main limiting factor in such networks, can be effectively contained using Interference Rejection Combining (IRC) re...

  16. HoB4 at high pressure and low temperature: an experimental and theoretical study

    DEFF Research Database (Denmark)

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

    2011-01-01

    Single crystals of HoB4 have been grown and used for synchrotron X-ray diffraction studies at pressures up to 23GPa and temperatures down to 100K. The experimental bulk modulus 195 ± 6GPa is in good agreement with 188.4 and 198.2GPa values calculated in the LSDA and LSDA+U approximations...

  17. 26 CFR 1.851-3 - Rules applicable to section 851(b)(4).

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 9 2010-04-01 2010-04-01 false Rules applicable to section 851(b)(4). 1.851-3 Section 1.851-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Regulated Investment Companies and Real Estate Investment Trusts § 1.851...

  18. Coxeter groups A4, B4 and D4 for two-qubit systems

    Indian Academy of Sciences (India)

    Abstract. The Coxeter–Weyl groups W(A4), W(B4) and W(D4) have proven very useful for two-qubit systems in quantum information theory. A simple technique is employed to construct the unitary matrix representations of the groups, based on quaternionic transformation of the usual reflection matrices. The von Neumann ...

  19. Gaseous swelling of B4C and UO2 fuel: similarities and differences

    International Nuclear Information System (INIS)

    Evdokimov, I.; Khoruzhii, O.; Kourtchatov, S.; Likhanskii, V.; Matweev, L.

    2001-01-01

    A major factor limiting the resource of control rods (CRs) for WWER-1000 reactors is their radiation damage. Radiation induced embrittlement of the CRs cladding, core swelling and gaseous internal pressure in CRs result in mechanical core-cladding interaction. This work is devoted to the physical analysis of processes that control the structural changes in neutron absorber elements with B 4 C under irradiation in water reactors. Particularly, the analysis of mechanisms of the helium porosity formation in B 4 C is undertaken. In view of the deficiency of experimental data on the subject, a fruitful approach to the problem is a comparative analysis of the swelling mechanisms in B 4 C absorber and UO 2 fuel. Using this similarity a phenomenological model of fission gas behavior in boron carbide is proposed. The model predictions for radial profile of 10 B burnup under influence of thermal and epithermal neutrons are compared with experimental results. The main results show that despite the external similarity of the process of fission gas accumulation in UO 2 and in B 4 C, phenomenology of gaseous swelling is much different for the fuel and the CR core. The reason for that difference is the distinction of physical conditions in irradiated fuel and CR core

  20. Fabrication and Tribological Behavior of Stir Cast Mg/B4C Metal Matrix Composites

    Science.gov (United States)

    Singh, Amandeep; Bala, Niraj

    2017-10-01

    Magnesium-based metal matrix composites (MMMCs) have emerged as good alternative material to conventional materials due to their promising advanced properties. In the present work, magnesium-based metal matrix composites (MMMCs) reinforced with B4C particles were successfully fabricated by cost-effective conventional stir casting technique. MMMCs with an average particle size of 63 µm and different weight percent (wt pct) of B4C between 3 and 12 were fabricated. Wear tests were carried out using a pin-on-disk against a steel disk under dry sliding condition at loads that varied between 1 and 5 kg at fixed sliding velocity of 1 m/s. The wear data clearly showed that wear resistance of cast composites is better than that of unreinforced magnesium, which is attributed to dispersion hardening caused by carbide particles. An increase in wt pct of B4C showed the wear resistance and hardness to increase significantly. The wear rate and coefficient of friction increased with an increase in applied load. The SEM and EDS analysis of the worn surfaces delineated the dominant wear mechanisms to be abrasion, adhesion, and oxidation under the different sliding conditions. At lower loads, the wear mechanism transformed from severe abrasive wear in pure magnesium (Mg) to mild abrasion, slight delamination, and oxidation in the Mg/12 wt pct B4C fabricated composite. At higher loads, severe abrasion, adhesion, delamination, and oxidation were found to be the major wear mechanisms in pure Mg, whereas in the Mg/12 wt pct B4C fabricated composites the corresponding mechanisms were mild abrasion, mild adhesion, slight delamination, and oxidation.

  1. Hot Workability and Flow Characteristics of Aluminum-5 wt.% B4C Composite

    Science.gov (United States)

    Gangolu, S.; Rao, A. G.; Prabhu, N.; Deshmukh, V. P.; Kashyap, B. P.

    2014-04-01

    Flow behavior of aluminum-5 wt.% boron carbide (Al-B4C) composite was investigated by carrying out compression tests over a range of strain rates (10-4-100 s-1) and temperatures (200-500 °C). The flow stress data obtained from these tests at true strain 0.5 were used to develop processing map. The stable and instable flow regimes in the map were characterized by the microstructural examination using Scanning Electron Microscopy and Electron Backscattered Diffraction. The optimum condition for processing of Al-5%B4C composite was found to lie between 425 and 475 °C at the strain rate of around 10-4 s-1. A strain-compensated Sellars-McG Tegart constitutive equation was established to model high-temperature deformation behavior of the material.

  2. B4C protective coating under irradiation by QSPA-T intensive plasma fluxes

    Science.gov (United States)

    Buzhinskij, O. I.; Barsuk, V. A.; Begrambekov, L. B.; Klimov, N. S.; Otroshchenko, V. G.; Putric, A. B.

    2016-12-01

    The effect of the QSPA-T pulsed plasma irradiation on the crystalline boron carbide B4C coating was examined. The duration of the rectangular plasma pulses was 0.5 ms with an interval of 5-10 min between pulses. The maximum power density in the central part of plasma stream was 1 GW/m2. The coating thickness varied from 20 to 40 μm on different surface areas. Modification of the surface layers and transformation of the coating at elevated temperature under plasma pulse irradiation during four successive series of impulses are described. It is shown that the boron carbide coating withstood the full cycle of tests under irradiation with 100 plasma pulses with peak power density of 1GW/m2. Constitutive surface deterioration was not detected and the boron carbide coating kept crystal structure B4C throughout the irradiation zone at the surface depth no less 2 μm.

  3. Modeling of wear behavior of Al/B4C composites produced by powder metallurgy

    International Nuclear Information System (INIS)

    Sahin, Ismail; Bektas, Asli; Guel, Ferhat; Cinci, Hanifi

    2017-01-01

    Wear characteristics of composites, Al matrix reinforced with B 4 C particles percentages of 5, 10,15 and 20 produced by the powder metallurgy method were studied in this study. For this purpose, a mixture of Al and B 4 C powders were pressed under 650 MPa pressure and then sintered at 635 C. The analysis of hardness, density and microstructure was performed. The produced samples were worn using a pin-on-disk abrasion device under 10, 20 and 30 N load through 500, 800 and 1200 mesh SiC abrasive papers. The obtained wear values were implemented in an artificial neural network (ANN) model having three inputs and one output using feed forward backpropagation Levenberg-Marquardt algorithm. Thus, the optimum wear conditions and hardness values were determined.

  4. Effects of phthalates on the human corneal endothelial cell line B4G12

    DEFF Research Database (Denmark)

    Krüger, Tanja; Cao, Yi; Kjærgaard, Søren K.

    2012-01-01

    Phthalates are industrial chemicals used in many cosmetics. We evaluated an in vitro model for eye irritancy testing using the human corneal endothelial cell line B4G12. Cell proliferation and toxicity were assessed after exposing to di-n-butyl phthalate (DBP), benzyl butyl phthalate (BBP), di-2......-ethylhexyl phthalate (DEHP), diisodecyl phthalate (DIDP), di-n-octyl phthalate (DnOP), and di-isononyl phthalate (DINP). Gene expression and secretion of inflammatory cytokines were evaluated after exposure to DBP. Decreased cell proliferation was observed for the phthalates DBP, BBP, and DEHP, and cell...... line B4G12 may be a potential model for inflammatory eye irritancy testing of phthalates....

  5. Cr/B4C multilayer mirrors: Study of interfaces and X-ray reflectance

    Science.gov (United States)

    Burcklen, C.; Soufli, R.; Dennetiere, D.; Polack, F.; Capitanio, B.; Gullikson, E.; Meltchakov, E.; Thomasset, M.; Jérome, A.; de Rossi, S.; Delmotte, F.

    2016-03-01

    We present an experimental study of the effect of layer interfaces on the x-ray reflectance in Cr/B4C multilayer interference coatings with layer thicknesses ranging from 0.7 nm to 5.4 nm. The multilayers were deposited by magnetron sputtering and by ion beam sputtering. Grazing incidence x-ray reflectometry, soft x-ray reflectometry, and transmission electron microscopy reveal asymmetric multilayer structures with a larger B4C-on-Cr interface, which we modeled with a 1-1.5 nm thick interfacial layer. Reflectance measurements in the vicinity of the Cr L2,3 absorption edge demonstrate fine structure that is not predicted by simulations using the currently tabulated refractive index (optical constants) values for Cr.

  6. On the phototransferred thermoluminescence in MgB4O7:Dy

    International Nuclear Information System (INIS)

    Richmond, R.G.

    1987-01-01

    On exposure to ionizing radiations, the normal traps in MgB 4 0 7 :Dy can be emptied by the readout process only or by annealing at suitable temperatures, leaving the deep traps still intact. Subsequently, it is possible to repopulate the dosimetric peak by illuminating with u.v. light. Charge carriers released from the traps during the second readout give rise to a thermoluminescent output proportional to the ionizing radiation exposure and the u.v. radiant energy. This is called phototransferred thermoluminescence (PTTL). The PTTL method can be utilized for the reassessment of the initial γ-ray exposure. This paper presents the measurements of the intrinsic response of the commercially available MgB 4 0 7 :Dy to u.v. radiation, with a demonstration of its use for γ-ray dose re-estimation using the PTTL technique. (author)

  7. Antenatal and postnatal diagnosis of coxsackie b4 infection: case series.

    Science.gov (United States)

    Hunt, Jennifer C; Schneider, Carol; Menticoglou, Savas; Herath, Jayantha; Del Bigio, Marc R

    2012-11-01

    Enteroviruses are a common cause of neonatal infection. In particular, Coxsackie B viruses are often associated with severe, fatal disease. The antenatal diagnosis of Coxsackie B viral infections is uncommon. We present a unique case of Coxsackie B4 virus ventriculitis and myocarditis causing fetal hydrops at 22 weeks gestation. Transmission was inferred by viral isolation from the amniotic fluid and by placental pathology. We also describe two additional cases of fatal neonatal Coxsackie B4 infection complicated by myocarditis and encephalitis with cerebral necrosis in a 4-day-old female and by myocarditis, spinal leptomeningitis, and hepatitis in a 4-day-old male. Transplacental acquisition of infection carries a poor prognosis. We propose that Coxsackie B virus should be considered in the investigation of nonimmune hydrops, particularly in the presence of cardiac dysfunction.

  8. Antenatal and Postnatal Diagnosis of Coxsackie B4 Infection: Case Series

    Directory of Open Access Journals (Sweden)

    Jennifer C. Hunt

    2012-11-01

    Full Text Available Enteroviruses are a common cause of neonatal infection. In particular, Coxsackie B viruses are often associated with severe, fatal disease. The antenatal diagnosis of Coxsackie B viral infections is uncommon. We present a unique case of Coxsackie B4 virus ventriculitis and myocarditis causing fetal hydrops at 22 weeks gestation. Transmission was inferred by viral isolation from the amniotic fluid and by placental pathology. We also describe two additional cases of fatal neonatal Coxsackie B4 infection complicated by myocarditis and encephalitis with cerebral necrosis in a 4-day-old female and by myocarditis, spinal leptomeningitis, and hepatitis in a 4-day-old male. Transplacental acquisition of infection carries a poor prognosis. We propose that Coxsackie B virus should be considered in the investigation of nonimmune hydrops, particularly in the presence of cardiac dysfunction.

  9. Effect of the leukotriene B4 receptor antagonist, SC-41930, on experimental allergic encephalomyelitis (EAE) in the guinea pig.

    Science.gov (United States)

    Fretland, D J; Widomski, D L; Shone, R L; Levin, S; Gaginella, T S

    1991-09-01

    The accepted model for the human demyelinating disease, multiple sclerosis (MS), is experimental allergic encephalomyelitis (EAE). We assessed the ability of SC-41930(7-[3(4-acetyl-3-methoxy-2-propyl-phenoxy)-propoxy]- 3,4-dihydro-8-propyl-2H-1-benzopyran-2-carboxyl acid), to modulate the symptoms of acute EAE generated in guinea pigs. Animals were pretreated with SC-41930 (20 mg/kg, i.p.) for two days followed by thrice-weekly maintenance. At day 52, a significant number of the SC-41930-treated animals were alive as compared to EAE alone. Control animals had an increase in body weight while EAE animals lost over 20% (p less than 0.5) of their body weight by day 18. SC-41930-treatment significantly reduced, but did not completely inhibit the cachectic response. The results indirectly implicate LTB4 in the pathogenesis of EAE. Agents that modify this model be useful in the treatment of human MS.

  10. Atomic structure and vibrational properties of icosahedral B$_4$C boron carbide

    OpenAIRE

    Lazzari, R.; Vast, N.; Besson, J. M.; Baroni, S.; Corso, A. Dal

    1999-01-01

    The atomic structure of icosahedral B$_4$C boron carbide is determined by comparing existing infra-red absorption and Raman diffusion measurements with the predictions of accurate {\\it ab initio} lattice-dynamical calculations performed for different structural models. This allows us to unambiguously determine the location of the carbon atom within the boron icosahedron, a task presently beyond X-ray and neutron diffraction ability. By examining the inter- and intra-icosahedral contributions ...

  11. ∆DNMT3B4-del Contributes to Aberrant DNA Methylation Patterns in Lung Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Mark Z. Ma

    2015-10-01

    Full Text Available Aberrant DNA methylation is a hallmark of cancer but mechanisms contributing to the abnormality remain elusive. We have previously shown that ∆DNMT3B is the predominantly expressed form of DNMT3B. In this study, we found that most of the lung cancer cell lines tested predominantly expressed DNMT3B isoforms without exons 21, 22 or both 21 and 22 (a region corresponding to the enzymatic domain of DNMT3B termed DNMT3B/∆DNMT3B-del. In normal bronchial epithelial cells, DNMT3B/ΔDNMT3B and DNMT3B/∆DNMT3B-del displayed equal levels of expression. In contrast, in patients with non-small cell lung cancer NSCLC, 111 (93% of the 119 tumors predominantly expressed DNMT3B/ΔDNMT3B-del, including 47 (39% tumors with no detectable DNMT3B/∆DNMT3B. Using a transgenic mouse model, we further demonstrated the biological impact of ∆DNMT3B4-del, the ∆DNMT3B-del isoform most abundantly expressed in NSCLC, in global DNA methylation patterns and lung tumorigenesis. Expression of ∆DNMT3B4-del in the mouse lungs resulted in an increased global DNA hypomethylation, focal DNA hypermethylation, epithelial hyperplastia and tumor formation when challenged with a tobacco carcinogen. Our results demonstrate ∆DNMT3B4-del as a critical factor in developing aberrant DNA methylation patterns during lung tumorigenesis and suggest that ∆DNMT3B4-del may be a target for lung cancer prevention.

  12. PDGFRA, HSD17B4 and HMGB2 are potential therapeutic targets in polycystic ovarian syndrome and breast cancer

    Science.gov (United States)

    Xu, Huiyu; Han, Yong; Lou, Jiaying; Zhang, Hongxian; Zhao, Yue; Győrffy, Balázs; Li, Rong

    2017-01-01

    To explore the key genes associated with both PCOS and breast cancer, we overlapped the synchronously differently expressed genes in two obese insulin-resistant GEO datasets in muscle tissue and genes exert essential roles in breast cancer prognosis together base on the following reasons: (1) Androgens excess is believed to contribute to the onset of both PCOS and breast cancer. (2) PCOS is usually complicated with metabolic symptoms, such as obesity and insulin-resistance. (3) Muscle is the main place where energy metabolism and material metabolism take place. Consequently, 53 genes were found, functionally enriched in pathways such as pyruvate metabolism, muscle system process and development of primary male sexual characteristics etc. We further lay our eyes on genes correlated with male sexual characteristics, which may be involved in the onset of both PCOS and breast cancer. Three genes were indicated to be associated with this process, including hydroxysteroid (17-beta) dehydrogenase 4/HSD17B4, platelet-derived growth factor receptor, alpha polypeptide/PDGFRA and high-mobility group box 2/HMGB2. Gene-drug interaction network about the three genes were then constructed. Drugs or chemicals that contribute to correcting the disorder of lipid metabolism were detected to restore the abnormal expression of the three genes in PCOS, such as simvastatin, bezafibrate, fenofibrate et al, which provide further choices for managing patients with PCOS. PMID:29050221

  13. Production of Fumonisin B-2 and B-4 by Aspergillus niger on Grapes and Raisins

    DEFF Research Database (Denmark)

    Mogensen, Jesper Mølgaard; Frisvad, Jens Christian; Thrane, Ulf

    2010-01-01

    The recent discovery of fumonisin production in Aspergillus niger, raises concerns about the presence of these mycotoxins in grapes and raisins as well as other commodities where A. niger is a frequent contaminant. Here we investigate the potential production of fumonisins in A. niger cultured...... on grapes and raisins. Sixty-six A. niger, 4 A. tubingensis, and 16 A. acidus strains isolated from raisins were tested for fumonisin production on laboratory media. Neither A. tubingensis nor A. acidus strains produced fumonisins, but 77% of A. niger strains did. None of the strains produced ochratoxin A....... Ten selected fumonisin producing A. niger strains were further able to produce fumonisin B2 and fumonisin B4 on grapes in the range 171−7841 μg fumonisin B2/kg and 14−1157 μg fumonisin B4/kg. Four selected strains were able to produce fumonisin B2 (5−6476 μg/kg) and fumonisin B4 (12−672 μg...

  14. Microstructure and mechanical properties of pressureless sintered B4C- C composite using phenolic resin

    Science.gov (United States)

    Nikravan, A.; Baharvandi, H. R.; Jebelli, F. B.; Abdizadeh, H.; Ehsani, N.

    2007-10-01

    Boron carbide is an extremely promising material for a variety of applications that require high hardness and good wear resistance. However, due to the very high sintering temperatures which are required for B4C densification, wide spread use of that is limited. Various solutions have been studied to modifying densification behavior of B4C. Pressureless sintering in the presence of different additives has been tried by researchers. The effect of additives such as TiB2, SiC, Al, B, ZrO2, talc and Si have been evaluated. It was shown that the densification and mechanical properties may be improved with sintering aids. The Effects of phenolic resin additive on the microstructure and mechanical properties of B4C were explained in this study. Experimental composition was batched corresponding from 0 to 10 wt% of the additive. All samples were sintered for 60 minutes at 2150°C. The heating and cooling rates were 10°C/min for all samples. It was found that below 7.5 wt% of phenolic resin additive, the density increased with additive increasing and above that, decreased by phenolic resin addition. Mechanical properties such as fracture toughness, strength and hardness increased as a result of densification enhancement.

  15. Evaluation of drilling Al/B4C composites with carbide drills

    Directory of Open Access Journals (Sweden)

    Ali Rıza Motorcu

    2016-08-01

    Full Text Available In this study, cutting forces and torque was evaluated through Taguchi Method (TM in the drilling of the high density B4C particle reinforced composites, which were produced through powder metallurgy-hot pressing method, with coated and uncoated carbide drills. Cutting speed (18, 25 and 35 m/min, feed rate (0.08, 0.112 and 0.16 mm/rev, coating properties (coated and uncoated and the amounts of particle reinforcement (5%, 10% and 15% B4C were used as the control factors. It was observed that the increased feed rate and particle reinforcement increased the axial force and torque, and decreased the cutting speed. The uncoated drills had a better performance than the coated drills. The amount of B4C reinforcement was observed to be the most effective parameter on the axial force and torque with the contribution ratios of 96.6% and 49.1%, respectively. Moreover, the correlation coefficients (R2 of the first order predictive equations developed for the axial force and torque were calculated as 0.895 and 0.854, respectively.

  16. Effects of Micro- and Nano-B4C Fillers on Mechanical Properties of Epoxy Composites

    International Nuclear Information System (INIS)

    Jun, Ji Heon; Kim, Jae Woo; Uhm, Young Rang; Rhee, Chang Kyu

    2010-01-01

    Use of nuclear energy always requires safe and efficient transportation and storage of the radioactive wastes. In this regard, development of light and durable materials to shield various radiations is very important. In order to shield neutrons emitted from the spent nuclear fuel, a composite system of epoxy resin and B 4 C filler has been introduced. In this system, high concentration of hydrogen and boron in epoxy matrix can effectively attenuate high-energy neutrons and absorb thermal neutrons, respectively. However, adding fillers into the epoxy matrix has been known to deteriorate the mechanical properties of the epoxy composite because the volume occupied by fillers is equal to the loss volume of matrix resin and adhesion between the particles and the epoxy resin is in general poor. The deterioration of mechanical properties of the boron-epoxy composite makes its application as a neutron shielding material difficult. It should provide a mechanical reliability to endure exterior stresses including sudden deformation, friction and thermal shock, etc. Thus, it is a key issue in producing an epoxy-filler composite to suppress mechanical deterioration while maintaining the shielding capability simultaneously. In this study, micro- and nano-B 4 C particles were dispersed in the three-different epoxy matrix systems. The mechanical properties of the composites were compared with the pure epoxy resin to assess the change of mechanical deterioration. The effect of B 4 C particle size on the mechanical properties of the epoxy composites was also investigated

  17. Expression of the Blood-Group-Related Gene B4galnt2 Alters Susceptibility to Salmonella Infection.

    Directory of Open Access Journals (Sweden)

    Philipp Rausch

    2015-07-01

    Full Text Available Glycans play important roles in host-microbe interactions. Tissue-specific expression patterns of the blood group glycosyltransferase β-1,4-N-acetylgalactosaminyltransferase 2 (B4galnt2 are variable in wild mouse populations, and loss of B4galnt2 expression is associated with altered intestinal microbiota. We hypothesized that variation in B4galnt2 expression alters susceptibility to intestinal pathogens. To test this, we challenged mice genetically engineered to express different B4galnt2 tissue-specific patterns with a Salmonella Typhimurium infection model. We found B4galnt2 intestinal expression was strongly associated with bacterial community composition and increased Salmonella susceptibility as evidenced by increased intestinal inflammatory cytokines and infiltrating immune cells. Fecal transfer experiments demonstrated a crucial role of the B4galnt2-dependent microbiota in conferring susceptibility to intestinal inflammation, while epithelial B4galnt2 expression facilitated epithelial invasion of S. Typhimurium. These data support a critical role for B4galnt2 in gastrointestinal infections. We speculate that B4galnt2-specific differences in host susceptibility to intestinal pathogens underlie the strong signatures of balancing selection observed at the B4galnt2 locus in wild mouse populations.

  18. Preparation and characterization of B4C coatings for advanced research light sources.

    Science.gov (United States)

    Störmer, Michael; Siewert, Frank; Sinn, Harald

    2016-01-01

    X-ray optical elements are required for beam transport at the current and upcoming free-electron lasers and synchrotron sources. An X-ray mirror is a combination of a substrate and a coating. The demand for large mirrors with single layers consisting of light or heavy elements has increased during the last few decades; surface finishing technology is currently able to process mirror lengths up to 1 m with microroughness at the sub-nanometre level. Additionally, thin-film fabrication is able to deposit a suitable single-layer material, such as boron carbide (B4C), some tens of nanometres thick. After deposition, the mirror should provide excellent X-ray optical properties with respect to coating thickness errors, microroughness values and slope errors; thereby enabling the mirror to transport the X-ray beam with high reflectivity, high beam flux and an undistorted wavefront to an experimental station. At the European XFEL, the technical specifications of the future mirrors are extraordinarily challenging. The acceptable shape error of the mirrors is below 2 nm along the whole length of 1 m. At the Helmholtz-Zentrum Geesthacht (HZG), amorphous layers of boron carbide with thicknesses in the range 30-60 nm were fabricated using the HZG sputtering facility, which is able to cover areas up to 1500 mm long by 120 mm wide in one step using rectangular B4C sputtering targets. The available deposition area is suitable for the specified X-ray mirror dimensions of upcoming advanced research light sources such as the European XFEL. The coatings produced were investigated by means of X-ray reflectometry and interference microscopy. The experimental results for the B4C layers are discussed according to thickness uniformity, density, microroughness and thermal stability. The variation of layer thickness in the tangential and sagittal directions was investigated in order to estimate the achieved level of uniformity over the whole deposition area, which is considerably

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

    Directory of Open Access Journals (Sweden)

    Dmytro Demirskyi

    2015-12-01

    Full Text Available The in situ synthesis/consolidation of B4C-TaB2 eutectic composites by spark plasma sintering (SPS is reported. The microstructure–property relations were determined for composites with the B4C-TaB2 eutectic composition as functions of TaB2 content, and TaB2-TaB2 interlamellar spacing. A clear maximum in fracture toughness was identified (∼4.5 MPa m1/2 for eutectic composites with interlamellar spacing between 0.9 and 1.1 μm. The composites with the hypereutectic composition of 40 mol.% TaB2 obtained by SPS exhibited lower Vickers hardness (25–26 GPa but higher indentation fracture toughness (up to 4.9 MPa m1/2 than eutectic composites with 30–35 mol.% of TaB2.

  20. La/B(4)C multilayer mirrors with an additional wavelength suppression.

    Science.gov (United States)

    Naujok, Philipp; Yulin, Sergiy; Bianco, Anna; Mahne, Nicola; Kaiser, Norbert; Tünnermann, Andreas

    2015-02-23

    In this paper, the authors report on La/B(4)C multilayer mirrors designed for an incidence angle of 45° with both maximum reflectivity at a wavelength of 6.7 nm and reflectivity suppression at a wavelength of 20.1 nm. These mirrors were deposited for the EIS-TIMER at the FERMI@Elettra Free Electron Laser. The multilayer structure and optical properties were characterized using grazing incidence X-ray reflectometry with Cu-K(α) radiation and EUV reflectometry in the spectral region of 6.5 - 21.0 nm. An anti-reflective coating designed at the wavelength of 20.1 nm had to be deposited on top of the high reflective La/B(4)C multilayer mirror optimized at a wavelength of 6.7 nm. Measured reflectivities of 53.4% at the wavelength of 6.72 nm and 0.15% at the wavelength of 20.1 nm were simultaneously achieved. It is shown that the reflectivity loss at the wavelength of 6.7 nm due to the utilization of antireflective coating designed at the wavelength of 20.1 nm can be minimized up to 1.0%.

  1. Battery for ECT Related Cognitive Deficits (B4ECT-ReCoDe): development and validation.

    Science.gov (United States)

    Viswanath, Biju; Harihara, Shashidhara N; Nahar, Abhinav; Phutane, Vivek Haridas; Taksal, Aarati; Thirthalli, Jagadisha; Gangadhar, Bangalore N

    2013-06-01

    The use of electroconvulsive therapy (ECT) in treatment of psychiatric disorders is associated with adverse cognitive effects. There is a need to develop a short assessment tool of cognitive functions during the course of ECT. This study aimed at developing and validating a short, sensitive battery to assess cognitive deficits associated with ECT in India. Battery for ECT Related Cognitive Deficits (B4ECT-ReCoDe), a brief cognitive battery (20-30 min) to assess verbal, visual, working and autobiographic memory, sustained attention, psychomotor speed and subjective memory impairment, was administered to 30 in-patients receiving bilateral ECT, one day after the 1st, 3rd and 6th ECT. Data was analysed using repeated measures analysis of variance and Pearson's correlation. Significant deficits were found in verbal, visual and autobiographic memory, psychomotor speed. Subjective experience of memory loss correlated positively with verbal memory impairment. B4ECT-ReCoDe, a brief, sensitive measure of cognitive impairments associated with ECT can be used in routine clinical practice. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Production and characterization of compounds based on MgB4O7 for application in dosimetry

    International Nuclear Information System (INIS)

    Souza, Luiza Freire de

    2016-01-01

    Many materials with luminescent properties are used for ionizing radiation dosimetry through the thermoluminescence (TL) and optically stimulated luminescence (OSL) techniques. Detectors based on lithium fluoride (LiF), calcium sulphate (CaSO 4 ) and aluminum oxide (Al 2 O 3 ), doped or codoped with various elements, are the TL or OSL commercial dosimeters most widely used currently. However, several researches are focused to the development of new TL /OSL materials in intention to enhance the dosimetric properties, in view that no TL/OSL dosimeter has all the ideal characteristics for monitoring the radiation. In this context, magnesium tetraborate (MgB 4 O 7 ), which has been presented in the literature as a material for dosimetry TL, was investigated in this work. As there are no reports on the structural characterization of this material or regarding to its applicability on OSL dosimetry, the proposal of the present work was to develop compounds based on MgB 4 O 7 , with different doping, by solid state synthesis. It was made the structural, optical, TL and OSL characterization of the compound to verify it feasibility for application on radiation dosimetry. Initially, it was determined the calcination temperature and time for MgB 4 O 7 formation, with the use of thermal analyses and x ray diffraction. The ideal calcination was found at 900 °C for 7 hours. It were produced , in powder form, the compounds: MgB 4 O 7 , MgB 4 O 7 :Dy, MgB 4 O 7 :Dy,Li, MgB 4 O 7 :Ce, MgB 4 O 7 :Ce,Li, MgB 4 O 7 :Nd and MgB 4 O 7 :Nd,Li. For TL and OSL analyses it were produced pellets sintering at 950 °C for 2 hours. The radioluminescence (RL) analyses of MgB 4 O 7 :Dy and MgB 4 O 7 :Dy,Li shows wavelength emissions at 490, 590, 670 and 760 nm. For MgB 4 O 7 :Ce and MgB 4 O 7 :Ce,Li RL was observed wide emission band in the ultraviolet region. For the MgB 4 O 7 :Nd and MgB 4 O 7 :Nd,Li RL were not observed emission from the ultraviolet to infrared. With the results obtained from

  3. Leukotriene enhances NMDA-induced inward currents in dorsal horn neurons of the rat spinal cord after peripheral nerve injury.

    Science.gov (United States)

    Kiyoyuki, Yasukuni; Taniguchi, Wataru; Okubo, Masamichi; Yamanaka, Hiroki; Kobayashi, Kimiko; Nishio, Naoko; Nakatsuka, Terumasa; Noguchi, Koichi

    2015-09-09

    LTB4 is classified as a leukotriene (LT), a group of lipid mediators that are derived from arachidonic acid. It is recognized that leukotrienes are involved in the pathogenesis of many diseases, including peripheral inflammatory pain. However, little is known about the effects of leukotrienes on the spinal dorsal horn during neuropathic pain. Previously, we reported that there was increased expression of 5-lipoxygenase (5-LO) at spinal microglia, and the leukotriene B4 receptor 1 (BLT1), a high affinity receptor of LTB4, in spinal neurons in spared nerve injury (SNI) model rats. In the present study, we examined the effects of LTB4 on spinal dorsal horn neurons in both naïve and SNI model rats using patch-clamp methods. Bath application of LTB4 did not change AMPA receptor-mediated spontaneous excitatory postsynaptic currents (sEPSCs) or membrane potentials. However, we found that LTB4 enhanced the amplitude of NMDA receptor-mediated sEPSCs and significantly increased exogenous NMDA-induced inward currents in SNI model rats. This increase of inward currents could be inhibited by a selective LTB4 antagonist, U75302, as well as a GDP-β-S, a G-protein inhibitor. These results indicate that both increased LTB4 from spinal microglia or increased BLT1 in spinal neurons after peripheral nerve injury can enhance the activity of NMDA receptors through intracellular G-proteins in spinal dorsal horn neurons. Our findings showed that LTB4, which may originate from microglia, can activate BLT1 receptors which are expressed on the membrane of spinal dorsal horn neurons during neuropathic pain. This glia-neuron interaction induces the enhancement of NMDA currents through intracellular G-proteins. The enhancement of NMDA receptor sensitivity of dorsal horn neurons may lead to central sensitization, leading to mechanical pain hypersensitivity.

  4. Expression of eicosanoid receptors subtypes and eosinophilic inflammation: implication on chronic rhinosinusitis

    Directory of Open Access Journals (Sweden)

    Van Cauwenberge Paul

    2006-05-01

    Full Text Available Abstract Background Eicosanoid receptors are G-protein-coupled receptors playing an important immunomodulatory role in airway diseases. However, there is little information on the expression of these receptors and their link with eosinophilic inflammation in paranasal sinus diseases. We aimed with this study to investigate the tissue expression of leukotrienes and prostaglandin E2 receptors in chronic rhinosinusitis patients and the link of this regulation with eosinophilic inflammation. Methods Samples were prepared from nasal tissue of patients with chronic rhinosinusitis without nasal polyps (CRS, n = 11, with nasal polyps (CRS-NP, n = 13 and healthy subjects (Controls, n = 6. mRNA expression of CysLT1, CysLT2, BLT1, BLT2, E-prostanoid receptors (EP1, EP2, EP3, EP4 and sol-IL-5Rα was determined by real-time PCR. Concentrations of PGE2, LTC4/D4/E4, LTB4 and sol-IL-5Rα were determined by ELISA and of ECP by ImmunoCap. Protein expression and tissue localization of eicosanoid receptors and activated eosinophils were evaluated by immunohistochemistry. Results CysLT1 mRNA expression was significantly increased in CRS-NP compared to CRS and controls, and CRS compared to controls, whereas CysLT2 mRNA was enhanced in both CRS groups without differences between them. Levels of both receptors correlated to the number of activated eosinophils, sol-IL-5Rα, ECP and LTC4/D4/E4 concentrations in the disease groups. PGE2 protein concentrations and prostanoid receptors EP1 and EP3 were down-regulated in the CRS-NP tissue vs. CRS and controls, whereas EP2 and EP4 expression was enhanced in CRS and CRS-NP patients vs. controls. No differences in BLT receptors were observed between patients and controls. Conclusion CyLTs receptors are up-regulated in nasal polyp tissue and their expression correlate with eosinophilic inflammation supporting previous results. Eicosanoid receptors mRNA pattern observed suggests that down-regulation of EP1 and EP3 in CRS-NP and

  5. 29 CFR 2520.104b-4 - Alternative methods of compliance for furnishing the summary plan description and summaries of...

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Alternative methods of compliance for furnishing the summary plan description and summaries of material modifications of a pension plan to a retired participant, a separated participant with vested benefits, and a beneficiary receiving benefits. 2520.104b-4 Section 2520.104b-4 Labor Regulations Relating to...

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  7. Enhancement of dispersion and adhesion of B4C particles in epoxy resin using direct ultrasonic excitation

    International Nuclear Information System (INIS)

    Jun, Jiheon; Kim, Jaewoo; Bae, Yeonjoo; Seo, Young Soo

    2011-01-01

    Highlights: → Enhanced adhesion and dispersion of B 4 C particles in epoxy resin was achieved. → FTIR spectrum was used for examination of B 4 C adhesion with epoxy resin. → Direct ultrasonic excitation causes enhanced surface treatment of B 4 C. → We developed an epoxy based neutron shield with higher mechanical properties. - Abstract: Enhancement of the mechanical properties of the B 4 C/epoxy composites, which is used as a neutron shield for spent nuclear fuel cask, was achieved by direct ultrasonic dispersion of the B 4 C particles in the hardener using an immersed horn, while those prepared without direct ultrasonic dispersion showed insufficient adhesion as well as some agglomerates in the epoxy resin. Degrees of agglomeration and adhesion were analyzed by means of the SEM images and the FTIR peaks belong to C-C stretching mode of the hardener ring, which was lowered and flattened by van der Waals interaction between the B 4 C particles and the hardener ring substituent. The tensile strength of the B 4 C/epoxy composites prepared by direct ultrasonic dispersion was maintained (or increased) compared to that for the neat epoxy matrix, while those prepared without ultrasonic dispersion were degraded significantly. Consequently, direct ultrasonic dispersion process developed in this investigation could achieve uniform dispersion as well as strong adhesion of the B 4 C particles in/with the epoxy matrix enhancing the material properties without any chemical treatment resulting unwanted impurities.

  8. [Association of cytochrome P450 2B4 with molecular chaperones in heterological expression in E coli].

    Science.gov (United States)

    Prozorovskiĭ, T V; Schunck, W H; Archakov, A I

    2001-01-01

    To produce a water-soluble form of microsomal P450 2B4, fusion proteins with glutathione-S-transpherase were genetically engineered. Specific proteolitic sites recognized by Factor Xa and Thrombin have been introduced into N-terminus of P450 2B4 (46-49), lacking signal anchor sequence (2-27). It was supposed that proteolysis at this site could give the possibility to produce protein lacking hydrophobic N-terminus sequence (1-49). However, it was shown that given region in P450 2B4 his resistant against specific proteinase action. Positive result has been obtained at specific proteolysis with IgA endoproteinase, recognizing the native sequence PPGP (31-34) in P450 2B4. Thus, at first time truncated form of cytochrome 2B4, lacking its 33 N-terminal amino acid residues has been created. It was found that the expression of genetically engineered variants of GST-2B4 in Escherichia coli is accompanied by tight complex formation with molecular chaperones GroEL and DnaK. Dissociation of the complex occurred after proteolysis in: linker sequence (position 6-7) between C-terminal part of GST domain and N-terminal part of 2B4, and also before N-terminal methionine 2B4 and at position 33-34 (2B4). These results suggest the possibility that interaction with a GroEL/DnaK molecular chaperones may be requirement for correct folding of eukaryotic cytochrome 2B4 during its biosynthesis in E. coli.

  9. TRAIL/DR5 signaling promotes macrophage foam cell formation by modulating scavenger receptor expression.

    Directory of Open Access Journals (Sweden)

    Fang Fang Liu

    Full Text Available Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L has been shown to have protective effects against atherosclerosis. However, whether TRAIL has any effects on expression of macrophage scavenger receptors and lipid uptake has not yet been studied. Macrophage lines RAW264.7 and THP-1, and mouse primary peritoneal macrophages, were cultured in vitro and treated with recombinant human TRAIL. Real-time PCR and western blot were performed to measure mRNA and protein expressions. Foam cell formation was assessed by internalization of acetylated and oxidized low-density lipoproteins (LDL. Apoptosis was measured by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. We found that TRAIL treatment increased expression of scavenger receptor (SR-AI and SR-BI in a time- and dose-dependent manner, and this effect was accompanied by increased foam cell formation. These effects of TRAIL were abolished by a TRAIL neutralizing antibody or in DR5 receptor-deficient macrophages. The increased LDL uptake by TRAIL was blocked by SR-AI gene silencing or the SR-AI inhibitor poly(I:C, while SR-BI blockade with BLT-1 had no effect. TRAIL-induced SR-AI expression was blocked by the inhibitor of p38 mitogen-activated protein kinase, but not by inhibitors of ERK1/2 or JNK. TRAIL also induced apoptosis in macrophages. In contrast to macrophages, TRAIL showed little effects on SR expression or apoptosis in vascular smooth muscle cells. In conclusion, our results demonstrate that TRAIL promotes macrophage lipid uptake via SR-AI upregulation through activation of the p38 pathway.

  10. Ceramic composite resistors of B4C modified by TIO2 and glass phase

    International Nuclear Information System (INIS)

    Klimiec, E.; Zaraska, W.; Stobiecki, T.

    1998-01-01

    Technical progress in the manufacturing technology of composite materials resulted in arising of new generation of bulk resistors, resistant to high levels of overloads and high temperature. These resistors can be applied in extremely heavy working conditions, for instance in cooperation with ignition circuits. The resistors investigated in our research were performed on the basis of ceramic composite consisted of semiconductor boron carbide B 4 C as conductive phase, aluminium oxide Al 2 O 3 and non-alkali glass as insulators and titanium dioxide TiO 2 . The technological procedure of the fabrication of resistors and the results of the tests, such as temperature dependence of the electrical resistance exploitation trials, are presented. (author)

  11. A polyethylene-B4C based concrete for enhanced neutron shielding at neutron research facilities

    Science.gov (United States)

    DiJulio, D. D.; Cooper-Jensen, C. P.; Perrey, H.; Fissum, K.; Rofors, E.; Scherzinger, J.; Bentley, P. M.

    2017-07-01

    We present the development of a specialized concrete for neutron shielding at neutron research facilities, based on the addition of hydrogen atoms in the form of polyethylene and also B4C for enhancing the neutron capture properties of the concrete. We show information on the mechanical properties of the concrete and the neutronics, in particular its relevance to modern spallation neutron sources, such as the European Spallation Source (ESS), currently under construction in Lund, Sweden. The new concrete exhibits a 15% lower mass density, a compressible strength of 50% relative to a standard concrete and a significant increase in performance of shielding against MeV neutrons and lower energies. The concrete could find application at the ESS in for example common shielding components, individual beamline shielding and instrument caves. Initial neutronic tests of the concrete, carried out at Lund University, have also verified the performance in the MeV neutron energy range and the results are presented.

  12. Electrochemistry in molten borates (Na2B4O7). Electroanalytical study of oxidoreducing systems

    International Nuclear Information System (INIS)

    Gregori de Pinochet, Ida de

    1978-01-01

    The results of a study developing suitable electroanalytical means of investigation such as linear sweep voltametry and chronopotentiometry in molten borates are described. It has been shown that the reduction of U (VI) to U (V) proceeds reversibly at a platinum electrode. The diffusion coefficient for the U (VI) species at 800 0 C and the activation energy of diffusion are respectively 4 10 -7 cm 2 s -1 and (34,8+-0,8) k cal mol -1 . UO 2 is an insoluble oxide in this fused salt. Electrochemical studies of As (V) and Cu (II) show a two step reduction process at a platinum electrode. According to the solvent system definitions, the 'acid-base' equilibrium B 4 O 7 2- reversible 2 BO 2 - + B 2 O 3 is characterised at 820 0 C by the constant Ksub(D)=10sup(0,4)molsup(3)kgsup(-3) estimated by potentiometric study at a boron electrode [fr

  13. Optimization of laser cladding of cold spray coatings with B4C and Ni powders

    Science.gov (United States)

    Fomin, V. M.; Golyshev, A. A.; Malikov, A. G.; Orishich, A. M.; Filippov, A. A.; Ryashin, N. S.

    2017-12-01

    In the present work, a combined method is considered for the production of a metal-matrix composite coating based on Ni and B4C. The coating is created by consistently applied methods: cold spray and laser cladding. The conditions of obtaining cermet layers are investigated depending on the parameters of laser cladding and cold spray. It is shown that the laser track structure significantly changes in accordance to the size of ceramic particles ranging 3-75 µm and its concentration. It is shown that the most perspective layers for additive manufacturing could be obtain from cold spray coatings with ceramic concentrations more than 50% by weight treated in the heat-conductivity laser mode.

  14. Moessbauer spectroscopy in nanocrystalline Fe88Zr7B4Cu1

    International Nuclear Information System (INIS)

    Navarro, I.

    1995-01-01

    Local structural changes during the crystallization process of initially amorphous Fe 88 Zr 7 B 4 Cu 1 (at %) have been investigated by means of Moessbauer spectroscopy at room temperature. In the as-cast state, no ferromagnetic phase has been detected. The crystallization process has been found to consist of two steps. In the first step (after annealing up to 500-650 C), precipitation of α-Fe (47-59%) takes place. The remaining amorphous matrix evolves to a ferromagnetic phase, although a small fraction of non-ferromagnetic phase (5-8%) is also detected during the crystallization process. Annealing at more elevated temperatures completely crystallizes the amorphous phase and three new crystalline subspectra are found. Correlations between the soft magnetic properties and these local structural changes are also discussed. ((orig.))

  15. Production of fumonisins B2 and B4 in Tolypocladium species.

    Science.gov (United States)

    Mogensen, Jesper Mølgaard; Møller, Kirsten Amalie; von Freiesleben, Pernille; Labuda, Roman; Varga, Elisabeth; Sulyok, Michael; Kubátová, Alena; Thrane, Ulf; Andersen, Birgitte; Nielsen, Kristian Fog

    2011-09-01

    Tolypocladium inflatum is known primarily for its production of the cyclosporines that are used as an immunosuppressive drug. However, we report here the production of the carcinogenic fumonisins B(2) and B(4) by this biotechnologically relevant fungal genus. These mycotoxins were detected in 11 strains tested from three species: Tolypocladium inflatum, T. cylindrosporum, and T. geodes. Production of fumonisins by Fusarium spp. and Aspergillus niger is highly medium- and temperature-dependent, so the effect of these parameters on fumonisin production by three T. inflatum strains was studied. Maximum production was achieved on media with high sugar content incubated at 25-30°C. Since these results demonstrate that fumonisin production could be widespread within the genus Tolypocladium, the potential contamination of commercial cyclosporine preparations with fumonisins needs to be investigated.

  16. Structural and electronic properties of Li(2)b(4)O(7).

    Science.gov (United States)

    Islam, Mazharul M; Maslyuk, Volodymyr V; Bredow, Thomas; Minot, Christian

    2005-07-21

    The reliability of various quantum-chemical approaches for the calculation of bulk properties of lithium tetraborate Li(2)B(4)O(7) was examined. Lattice parameters and the electronic structure obtained with density-functional theory (DFT), with DFT-Hartree-Fock (HF) hybrid methods, and with the semiempirical method MSINDO were compared to available experimental data. We also compared the results at DFT level using different wave functions, either based on linear combinations of atom-centered orbitals (LCAO), or on plane waves, as implemented in the crystalline orbital programs CRYSTAL and VASP. The basis set dependence of calculated properties was investigated for the LCAO method. In the plane wave approach ultrasoft pseudopotentials (US PP), and projector-augmented wave (PAW) potentials were used to represent the core electrons. For all methods under consideration, the calculated Li(2)B(4)O(7) structure parameters are close to each other and agree within a few percent with measured values. A more pronounced method dependence was found for the band structure, the band gap and the cohesive energy. Closest agreement between theoretical and experimental results for the band gap was obtained with the DFT-HF hybrid methods while pure DFT methods underestimate and HF based methods overestimate the measured value. It was found that the calculated band gap strongly depends on the atomic basis set in the LCAO approach. The description of the core electrons considerably affects the cohesive energy obtained with the plane wave approach. Atomic charges based on a Mulliken analysis were compared to effective charges obtained from Raman spectroscopy. Electron density maps are used to analyze the character of B-O and Li-O interactions.

  17. SLAMF6 and 2B4: Roles and modes of action in normal immunity ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    A functioning immune system is critical for successful treatment of cancer. Recent studies have shown an improvement of the immune response against cancer triggered by new drugs that block the function of certain types of receptors at the surface of immune cells. This project seeks to understand the role of two new ...

  18. Thermoluminescence and radioluminescence properties of tissue equivalent Cu-doped Li2B4O7 for radiation dosimetry

    International Nuclear Information System (INIS)

    Cruz Z, E.; Furetta, C.; Marcazzo, J.; Santiago, M.; Guarneros, C.; Pacio, M.; Palomino, R.

    2015-10-01

    Thermoluminescence (Tl) and radioluminescence (Rl) properties of lithium tetraborate (Li 2 B 4 O 7 ) doped with different concentration of copper (0.25, 0.5, 1 wt %) under gamma and beta irradiation has been investigated. The feasibility of using this borate in radiation dosimetry at low doses has been evaluated. Tissue equivalent Li 2 B 4 O 7 was prepared by solid state reaction using mixing stoichiometric compositions of lithium carbonate (Li 2 CO 3 ) and boric acid (H 3 BO 3 ) and a solution of CuCl 2 as dopant. The glow curve, of the most efficient copper doped borate (Li 2 B 4 O 7 :Cu 0.5 wt %), shows a main stable peak centered at 225 degrees C and a second low temperature peak centered at 80 degrees C. The low temperature peak disappears completely after 24 hours of storage in darkness and at room temperature or after an annealing at 120 degrees C for 10 seconds. The main peak of the Li 2 B 4 O 7 :Cu remains constant. The Tl response of Li 2 B 4 O 7 :Cu shows good linearity in the analyzed dose range. The stability and repeatability of Rl signals of the borate have been studied and the Li 2 B 4 O 7 :Cu (0.5 wt %) shown the higher Rl emission and a stable and repetitive response. Results show that Li 2 B 4 O 7 :Cu has prospects to be used in gamma and beta radiation dosimetry. (Author)

  19. High-temperature characteristics of 20MnB4 and 30MnB4 micro-addition cold upsetting steels and C45 and C70 high-carbon-steels

    Directory of Open Access Journals (Sweden)

    S. Sawicki

    2016-10-01

    Full Text Available The paper analyzes the high-temperature plasticity characteristics of 20MnB4 and 30MnB4 with micro-additives, intended for cold upsetting and high-carbon steels C45 and C70 in the “solid phase-liquid” during heating and cooling. The investigation was conducted to determine the plastic formability of the examined alloy under hot plastic working conditions. Experiments were carried out on the simulator Gleeble 3800 with the aim of determining the susceptibility of 20MnB4, 30MnB4, C45 and C70 steels to cracking at high temperature. The nil strength (NST, nil ductility (NDT and ductility recovery temperatures (DRT, and the fracture toughness factor and the BRT (brittleness temperature range have been determined.

  20. Thermoluminescence Material Li2B4O7:Cu,Ag,P For Dosimeter In The Radiotherapy

    International Nuclear Information System (INIS)

    Bui The Huy; Vo Thu Ha; Bui Minh Ly; Vu Xuan Quang

    2008-01-01

    The material Li 2 B 4 O 7 :Cu has effective atomic number 7.3. This value is equal to one of soft tissue, which is an important factor for radiotherapy dosimetry. However, there is a difficult technological problem and so it is used under the powder form in bags. In order to increase sensitivity and capability reuse, we have prepared Li 2 B 4 O 7 :Cu,Ag,P. Primarily we have successfully prepared this material in pellet form with 2 times more sensitive than Li 2 B 4 O 7 :Cu. (author)

  1. Comparison of microstructural and mechanical properties of Al–TiC, Al–B4C and Al–TiC–B4C composites prepared by casting techniques

    International Nuclear Information System (INIS)

    Mazaheri, Y.; Meratian, M.; Emadi, R.; Najarian, A.R.

    2013-01-01

    In the present work, production of Al–10%TiC, Al–10% B 4 C, Al–5%TiC–5%B 4 C (volume fraction) composites by casting techniques were studied. However, casting techniques suffers from poor incorporation and distribution of the reinforcement particles in the matrix. These problems become especially significant as the reinforcement size decreases due to greater agglomeration tendency and reduced wettability of the particles with the melt. Microstructure characterization of the composite samples was investigated by using scanning electron microscopy (SEM) equipped with energy dispersive spectroscopy (EDS) and X-ray diffractometer (XRD).The results showed heat treatment of B 4 C particles and addition of TiC particles with the flux improved the wettability and incorporation of reinforcement particles into melt. Mechanical characterization of samples showed that maximum hardness had belonged to Al–5%TiC–5%B 4 C composite, maximum yield and tensile strength had belonged to Al–10%B 4 C composite and maximum elongation had belonged to Al–10%TiC composite. Furthermore, wear properties of composites revealed the better behavior for Al–B 4 C composite.

  2. Enterococcus faecalis PrgJ, a VirB4-like ATPase, mediates pCF10 conjugative transfer through substrate binding.

    Science.gov (United States)

    Li, Feng; Alvarez-Martinez, Cristina; Chen, Yuqing; Choi, Kyoung-Jae; Yeo, Hye-Jeong; Christie, Peter J

    2012-08-01

    The Enterococcus faecalis prg and pcf genes of plasmid pCF10 encode a type IV secretion system (T4SS) required for conjugative transfer. PrgJ is a member of the VirB4 family of ATPases that are universally associated with T4SSs. Here, we report that purified PrgJ dimers displayed ATP binding and hydrolysis activities. A PrgJ nucleoside triphosphate (NTP) binding site mutation (K471E) slightly diminished ATP binding but abolished ATP hydrolysis in vitro and blocked pCF10 transfer in vivo. As shown with affinity pulldown assays, PrgJ and the K471E mutant protein interacted with the substrate receptor PcfC and with relaxase PcfG and accessory factor PcfF, which together form the relaxosome at the oriT sequence to initiate plasmid processing. The purified PrgJ and K471E proteins also bound single- and double-stranded DNA substrates without sequence specificity in vitro, and both PrgJ derivatives bound pCF10 in vivo by a mechanism dependent on an intact oriT sequence and cosynthesis of PcfC, PcfF, and PcfG, as shown by a formaldehyde-cross-linking assay. Our findings support a model in which the PcfC receptor coordinates with the PrgJ ATPase to drive early steps of pCF10 processing/transfer: (i) PcfC first binds the pCF10 relaxosome through contacts with PcfF, PcfG, and DNA; (ii) PcfC delivers the plasmid substrate to PrgJ; and (iii) PrgJ catalyzes substrate transfer to the membrane translocase. Substrate engagement with a VirB4-like subunit has not been previously described; consequently, our studies point to a novel function for these signature T4SS ATPases in mediating early steps of type IV secretion.

  3. Investigation on microstructural and mechanical properties of B4C–aluminum matrix composites prepared by microwave sintering

    Directory of Open Access Journals (Sweden)

    Ehsan Ghasali

    2015-10-01

    Full Text Available B4C reinforced aluminum composites were fabricated by microwave heating of the mixture of B4C (10, 15 and 20 wt% and aluminum powders at 650, 750, 850 and 950 °C. The effect of different amounts of B4C on the microstructure and mechanical properties of aluminum matrix was examined. The maximum bending (238 ± 10 MPa and compressive strength (330 ± 10 MPa values were measured for composites sintered at 950 and 750 °C, respectively. The maximum hardness (112 Vickers was measured for Al–20 wt% B4C composite sintered at 850 °C. XRD investigations showed the decomposition of boron carbide and also the formation of Al3BC by heating the composites at 850 °C. SEM micrographs showed uniform distribution of reinforcement particles in Al matrix.

  4. Spectral characterisation of aperiodic normal-incidence Sb/B4C multilayer mirrors for the λ < 124 Å range

    Science.gov (United States)

    Vishnyakov, E. A.; Kopylets, I. A.; Kondratenko, V. V.; Kolesnikov, A. O.; Pirozhkov, A. S.; Ragozin, E. N.; Shatokhin, A. N.

    2018-03-01

    Three broadband aperiodic Sb/B4C multilayer mirrors were synthesised for the purposes of soft X-ray optics and spectroscopy in the wavelength range beyond the L-edge of Si (λ matrix with 13 × 13 μm sized pixels). The experimental spectra are compared with theoretical calculations. The effect of lower antimony and B4C layer densities on the reflection spectra is discussed.

  5. PMCA4 (ATP2B4 mutation in familial spastic paraplegia.

    Directory of Open Access Journals (Sweden)

    Miaoxin Li

    Full Text Available Familial spastic paraplegia (FSP is a heterogeneous group of disorders characterized primarily by progressive lower limb spasticity and weakness. More than 50 disease loci have been described with different modes of inheritance. In this study, we identified a novel missense mutation (c.803G>A, p.R268Q in the plasma membrane calcium ATPase (PMCA4, or ATP2B4 gene in a Chinese family with autosomal dominant FSP using whole-exome sequencing and confirmed with Sanger sequencing. This mutation co-segregated with the phenotype in the six family members studied and is predicted to be pathogenic when multiple deleteriousness predictions were combined. This novel R268Q mutation was not present in over 7,000 subjects in public databases, and over 1,000 Han Chinese in our database. Prediction of potential functional consequence of R268Q mutation on PMCA4 by computational modeling revealed that this mutation is located in protein aggregation-prone segment susceptible to protein misfolding. Analysis for thermodynamic protein stability indicated that this mutation destabilizes the PMCA4 protein structure with higher folding free energy. As PMCA4 functions to maintain neuronal calcium homeostasis, our result showed that calcium dysregulation may be associated with the pathogenesis of FSP.

  6. Machinability Studies on Turning Al 6061alloy with 10% Reinforcement of B4C on MMC

    Directory of Open Access Journals (Sweden)

    Srivathsan A.

    2016-01-01

    Full Text Available Aluminum Boron Carbide Metal Matrix Composites (Al-MMC have revolutionized aeronautical and automobile industries, in the recent times due to their exceptional mechanical and physical properties. However it is seen that the machinability of these composites is greatly reduced by the hardness of constituent reinforcement particles. Moreover these constituent reinforcement particles serve as disadvantage by increasing tool wear accompanying undesirable depression in life of tool. This paper presents the experimental investigations on turning of Al6061 matrix metal reinforced with 10 % by weight of boron carbide (B4Cp particles - which was fabricated using Stir casting method. Fabricated samples are turned on medium duty lathe of 2kW spindle power with Polycrystalline Diamond (PCD inserts of 1500 grade at various cutting conditions by varying parameters. Hence, parameters such as power consumed by main spindle, machined surface roughness and tool wear are studied and recorded. Furthermore, study results are supported using concurring images obtained from Scanning Electron Microscopy (SEM. It is observed that surface finish and power consumed for 1500 grade insert are comparatively better at higher cutting speeds. Additionally it is observed that tool wear is strongly dependent on abrasive hard reinforcement particles.

  7. Degradation and oxidation of B 4C control rod segments at high temperatures

    Science.gov (United States)

    Steinbrück, M.

    2010-05-01

    Extensive series of test were performed of the degradation of boron carbide absorber rods and the oxidation of the resultant absorber melts. Various types of control rod segments made of commercial materials used in French 1300 MW PWRs were investigated in the temperature range between 800 °C and 1700 °C in a steam atmosphere. The gaseous reaction products were analyzed quantitatively by mass spectroscopy for evaluation of the oxidation rates. Extensive post-test examinations were performed by light microscopy, scanning electron microscopy as well as EDX and Auger spectroscopy. Rapid melt formation due to eutectic interactions of stainless steel (cladding tube) and B 4C, on the one hand, and steel and Zircaloy-4 (guide tube), on the other hand, was observed at temperatures above 1250 °C. Complex multi-component, multi-phase melts were produced. ZrO 2 oxide scale on the outside kept the melt within the guide tube, thus preventing its early relocation and oxidation. Rapid oxidation of the absorber melts and remaining boron carbide pellets took place after failure of the protective oxide shell above 1450 °C. Only very little methane was produced in these tests which is of interest in fission product gas chemistry because of the production of organic iodine.

  8. Electrochemical Polishing Applications and EIS of a Vitamin B4-Based Ionic Liquid

    International Nuclear Information System (INIS)

    Wixtrom, Alex I.; Buhler, Jessica E.; Reece, Charles E.; Abdel-Fattah, Tarek M.

    2013-01-01

    Modern particle accelerators require minimal interior surface roughness for Niobium superconducting radio frequency (SRF) cavities. Polishing of the Nb is currently achieved via electrochemical polishing with concentrated mixtures of sulfuric and hydrofluoric acids. This acid-based approach is effective at reducing the surface roughness to acceptable levels for SRF use, but due to acid-related hazards and extra costs (including safe disposal of used polishing solutions), an acid-free method would be preferable. This study focuses on an alternative electrochemical polishing method for Nb, using a novel ionic liquid solution containing choline chloride, also known as Vitamin B 4 (VB 4 ). Potentiostatic electrochemical impedance spectroscopy (EIS) was also performed on the VB4-based system. Nb polished using the VB4-based method was found to have a final surface roughness comparable to that achieved via the acid-based method, as assessed by atomic force microscopy (AFM). These findings indicate that acid-free VB 4 -based electrochemical polishing of Nb represents a promising replacement for acid-based methods of SRF cavity preparation

  9. Fine Structure Study of the Plasma Coatings B4C-Ni-P

    Science.gov (United States)

    Kornienko, E. E.; Bezrukova, V. A.; Kuz'min, V. I.; Lozhkin, V. S.; Tutunkova, M. K.

    2017-12-01

    The article considers structure of coatings formed of the B4C-Ni-P powder. The coatings were deposited using air-plasma spraying with the unit for annular injection of powder. The pipes from steel 20 (0.2 % C) were used as a substrate. The structure and phase composition of the coatings were studied by optical microscopy, scanning electron microscopy, transmission electron microscopy and X-ray diffractometry. It is shown that high-density composite coatings consisting of boron carbide particles distributed in the nickel boride metal matrix are formed using air-plasma spraying. The areas with round inclusions characterized by the increased amount of nickel, phosphorus and boron are located around the boron carbide particles. Boron oxides and nickel oxides are also present in the coatings. Thin interlayers with amorphous-crystalline structure are formed around the boron carbide particles. The thickness of these interlayers does not exceed 1 μm. The metal matrix material represents areas with nanocrystalline structure and columnar crystals.

  10. Grazing incidence Fe-line telescopes using W/B4C multilayers

    DEFF Research Database (Denmark)

    Joensen, K. D.; Gorenstein, P.; Christensen, Finn Erland

    1995-01-01

    The loss of throughput observed at higher energies for traditional grazing-incidence X-ray telescopes coated with high-Z elements can be partly countered by employing multilayers on the outermost reflectors. Using 8-keV reflectivity data from a periodic W/B4C multilayer, the expected performance...... of intermediate-sized telescopes of (1) the nested Kirkpatrick-Baez geometry and (2) the conical approximation to a nested Wolter-I geometry is computed. Depending on the multilayer design, the throughput was increased by a factor of 3 to 5 in a 1.5-keV wide band, or by 30% to 100% in a 3-keV-wide band. This gain...... is obtained at the expense of a 20% to 30% loss of throughput over the 2-to 4-keV band. These designs lend themselves well to astrophysics missions, such as spectroscopy of the H- and He-like iron emission lines (6.4 to 7.1 keV). The technology for multilayer coating, mounting, and configuring of the flat...

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

    Science.gov (United States)

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

    2014-12-20

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

  12. Analytical support for the B4C control rod test QUENCH-07

    International Nuclear Information System (INIS)

    Homann, C.; Hering, W.; Fernandez Benitez, J.A.; Ortega Bernardo, M.

    2003-04-01

    Degradation of B 4 C absorber rods during a beyond design accident in a nuclear power reactor may be a safety concern. Among others, the integral test QUENCH-07 is performed in the FZK QUENCH facility and supported by analytical work within the Euratom Fifth Framework Programme on Nuclear Fission Safety to get a more profound database. Since the test differed substantially from previous QUENCH tests, much more work had to be done for pretest calculations than usual to guarantee the safety of the facility and to derive the test protocol. Several institutions shared in this work with different computer code systems, as used for nuclear reactor safety analyses. Due to this effort, problems could be identified and solved, leading to several modifications of the originally planned test conduct, until a feasible test protocol could be derived and recommended. All calculations showed the same trends. Especially the high temperatures and hence the small safety margin for the facility were a concern. In this report, contributions of various authors, engaged in this work, are presented. The test QUENCH-07 and the related computational support by the engaged institutions were co-financed by the European Community under the Euratom Fifth Framework Programme on Nuclear Fission Safety 1998 - 2002 (COLOSS Project, contract No. FIKS-CT-1999-00002). (orig.)

  13. Umifenovir effectively inhibits IL-10 dependent persistent Coxsackie B4 virus infection.

    Science.gov (United States)

    Zhang, Shilin; Zhi, Chenyang; Li, Hongrui; Huang, Dianshuai; Fan, Qingjie; Cui, Jiuwei; Liang, Chongyang

    2017-05-01

    Coxsackie virus cannot be completely eliminated due to restrictive replication and impaired immune response, thus causing persistent infection. IL-10 plays a decisive role in the course of persistent viral infection. Umifenovir is a broad-spectrum antiviral drug, with certain treatment effects on Coxsackie virus infection. Previously, we showed that in addition to inhibiting Coxsackie B4 (CVB4) infection, Umifenovir also down-regulates IL-10 induced by persistent CVB4 virus infection in vitro and in vivo. Here, BALB/c mouse spleen cells infected with CVB4 were used as a model to explore the mechanism by which Umifenovir affects IL-10 expression. We found that subcellular localization of p38 and MAPK-activated protein kinase 2 (MK2) played a very important role in IL-10 secretion, and Umifenovir significantly prevented p38-MK2 complex from exiting the cell nucleus. This in turn blocked the biological functions of the latter pathway, and inhibited the high expression of IL-10 induced by CVB4. These findings suggest that Umifenovir is a potential anti-CVB4 drug; most importantly, Umifenovir could be used to treat IL-10 induced persistent viral infection. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Cutting Edge: 2B4-Mediated Coinhibition of CD4+ T Cells Underlies Mortality in Experimental Sepsis.

    Science.gov (United States)

    Chen, Ching-Wen; Mittal, Rohit; Klingensmith, Nathan J; Burd, Eileen M; Terhorst, Cox; Martin, Greg S; Coopersmith, Craig M; Ford, Mandy L

    2017-09-15

    Sepsis is a leading cause of death in the United States, but the mechanisms underlying sepsis-induced immune dysregulation remain poorly understood. 2B4 (CD244, SLAM4) is a cosignaling molecule expressed predominantly on NK cells and memory CD8 + T cells that has been shown to regulate T cell function in models of viral infection and autoimmunity. In this article, we show that 2B4 signaling mediates sepsis lymphocyte dysfunction and mortality. 2B4 expression is increased on CD4 + T cells in septic animals and human patients at early time points. Importantly, genetic loss or pharmacologic inhibition of 2B4 significantly increased survival in a murine cecal ligation and puncture model. Further, CD4-specific conditional knockouts showed that 2B4 functions on CD4 + T cell populations in a cell-intrinsic manner and modulates adaptive and innate immune responses during sepsis. Our results illuminate a novel role for 2B4 coinhibitory signaling on CD4 + T cells in mediating immune dysregulation. Copyright © 2017 by The American Association of Immunologists, Inc.

  15. Progress on B4C control rod modeling in RELAP/SCDAPSIM with application to quench and Phebus

    International Nuclear Information System (INIS)

    Kawahara, Keisuke; Hohorst, Judith K.; Allison, Chris M.

    2014-01-01

    The RELAP/SCDAPSIM code is designed to predict the behavior of reactor systems during normal and accident conditions. RELAP/SCDAPSIM/MOD3.5 is an experimental version of the code with the most advanced fuel and severe accident behavior models and correlations. It includes modeling improvements that were specifically added to support (a) the ongoing experimental severe accident programs in Europe and Japan and (b) the analysis and assessment activities related to the accident at the Fukushima Daiichi NPS. One of the improved models describes the behavior of cylindrical B 4 C control rods used in selected PWR designs and in integral experiments used to assess the heating and melting of PWR, BWR, and VVER assemblies. It replaces an older model that was originally developed by the US Nuclear Regulatory Commission in the mid- 1980's. It includes a combination of new and improved models and correlations to more accurately describe (a) eutectic reactions between Zircaloy, B 4 C, and stainless steel, (b) oxidation for B 4 C, Zircaloy, and stainless steel, and (c) the effects of the gap between the Zircaloy guide tube and the stainless steel sheath surrounding B 4 C pellets used in many control rod designs. This paper will discuss the development of the new model and validation of the model using the PHEBUS B 4 C test, FPT-3, and the KIT quench experiments with a central B 4 C control rod. (authors)

  16. Characterization of a chitinase with antifungal activity from a native Serratia marcescens B4A

    Directory of Open Access Journals (Sweden)

    Mandana Zarei

    2011-09-01

    Full Text Available Chitinases have the ability of chitin digestion that constitutes a main compound of the cell wall in many of the phytopathogens such as fungi. In the following investigation, a novel chitinase with antifungal activity was characterized from a native Serratia marcescens B4A. Partially purified enzyme had an apparent molecular mass of 54 kDa. It indicated an optimum activity in pH 5 at 45ºC. Enzyme was stable in 55ºC for 20 min and at a pH range of 3-9 for 90 min at 25ºC. When the temperature was raised to 60ºC, it might affect the structure of enzymes lead to reduction of chitinase activity. Moreover, the Km and Vmax values for chitin were 8.3 mg/ml and 2.4 mmol/min, respectively. Additionally, the effect of some cations and chemical compounds were found to stimulate the chitinase activity. In addition, Iodoacetamide and Idoacetic acid did not inhibit enzyme activity, indicating that cysteine residues are not part of the catalytic site of chitinase. Finally, chitinase activity was further monitored by scanning electronic microscopy data in which progressive changes in chitin porosity appeared upon treatment with chitinase. This enzyme exhibited antifungal activity against Rhizoctonia solani, Bipolaris sp, Alternaria raphani, Alternaria brassicicola, revealing a potential application for the industry with potentially exploitable significance. Fungal chitin shows some special features, in particular with respect to chemical structure. Difference in chitinolytic ability must result from the subsite structure in the enzyme binding cleft. This implies that why the enzyme didn't have significant antifungal activity against other Fungi.

  17. Studies on shallow traps in Li2B4O7:Eu,Mn

    International Nuclear Information System (INIS)

    Drozdowski, Winicjusz; Brylew, Kamil; Kaczmarek, Sławomir M.; Piwowarska, Danuta; Nakai, Yosuke; Tsuboi, Taiju; Huang, Wei

    2014-01-01

    Li 2 B 4 O 7 (LTB) single crystals doped with 0.5 mol% Mn and 0.005 mol% Eu have been grown by the Czochralski method. The presence of Eu 3+ has been confirmed by photoluminescence spectra of non-irradiated crystals, whereas the presence of Mn 2+ by absorption spectra of gamma-irradiated ones, as well as by EPR measurements. Unlike in most thermoluminescence studies on pure and doped LTB, performed usually above 300 K, glow curves have been recorded between 10 and 300 K in order to focus the attention on shallow traps. A broad, intense glow peak is observed around 80 K, with three weaker peaks at 205, 255, and 280 K. Based on supplementary T max  − T stop experiments, the trap parameters have been derived assuming that the glow curve is in fact formed by a superposition of a double Gaussian band related to a quasi-continuous distribution of trapping levels, and several glow peaks produced by discrete traps. The nature of the traps is also discussed. - Highlights: • Radioluminescence spectra of LTB:Eu,Mn have been measured at various temperatures. • Glow curves of LTB:Eu,Mn have been recorded between 10 and 300 K. • Thermoluminescence studies have been extended with the T max  − T stop method. • Trap parameters related to particular glow peaks have been derived. • Besides discrete traps a quasi-continuous distribution has been found

  18. New coxsackievirus B4 genotype circulating in Inner Mongolia Autonomous Region, China.

    Directory of Open Access Journals (Sweden)

    Xiaoling Tian

    Full Text Available Hand, foot, and mouth disease (HFMD surveillance was initiated in the Inner Mongolia Autonomous Region of China in 2007, a crucial scrutiny for monitoring the prevalence of enterovirus serotypes associated with HFMD patients. However, this surveillance mostly focused on enterovirus 71 (EV-A71 and coxsackievirus A16; therefore, information on other enterovirus serotypes is limited. To identify the other circulating enterovirus serotypes in the HFMD outbreaks in Inner Mongolia in 2010, clinical samples from HFMD patients were investigated. Six coxsackievirus B4 (CVB4 strains were isolated and phylogenetic analyses of VP1 sequences were performed. Full-length genome sequences of two representative CVB4 isolates were acquired and similarity plot and bootscanning analyses were performed. The phylogenetic dendrogram indicated that all CVB4 strains could be divided into 5 genotypes (Genotypes I-V with high bootstrap support (90-100%. The CVB4 prototype strain (JVB was the sole member of genotype I. CVB4 strains belonging to genotype II, which were once common in Europe and the Americas, seemingly disappeared and gave way to genotype III and IV strains, which appear to be the dominant circulating strains in the world. All Chinese CVB4 strains belonged to Genotype V, a newly identified genotype supported by a high bootstrap value (100%, and are circulating only in mainland of China. Intertypic recombination occurred in the Chinese CVB4 strains with novel unknown serotype EV-B donor sequences. Two Chinese CVB4 strains had a virulent residue at position 129 of VP1, and one strain also had a virulent residue at position 16 of VP4. Increased surveillance is needed to monitor the emergence of new genetic lineages of enteroviruses in areas that are often associated with large-scale outbreaks. In addition, continued monitoring of enteroviruses by clinical surveillance and genetic characterization should be enhanced.

  19. Low-pressure RF remote plasma cleaning of carbon-contaminated B4C-coated optics

    Science.gov (United States)

    Moreno Fernández, H.; Thomasset, M.; Sauthier, G.; Rogler, D.; Dietsch, R.; Barrett, R.; Carlino, V.; Pellegrin, E.

    2017-05-01

    Boron carbide (B4C) - due to its exceptional mechanical properties - is one of the few existing materials that can withstand the extremely high brilliance of the photon beam from free electron lasers (FELs) and is thus of considerable interest for optical applications in this field. However, as in the case of many other optics operated at modern accelerator-, plasma-, or laser-based light source facilities, B4C-coated optics are subject to ubiquitous carbon contaminations. These contaminations - that are presumably produced via cracking of CHx and CO2 molecules by photoelectrons emitted from the optical components - represent a serious issue for the operation of the pertinent high performance beamlines due to a severe reduction of photon flux and beam coherence, not necessarily restricted to the photon energy range of the carbon K-edge. Thus, a variety of B4C cleaning technologies have been developed at different laboratories with varying success [1]. Here, we present a study regarding the low-pressure RF plasma cleaning of a series of carbon-contaminated B4C test samples via an inductively coupled O2/Ar and Ar/H2 remote RF plasma produced using the IBSS GV10x plasma source following previous studies using the same RF plasma source [2, 3]. Results regarding the chemistry, morphology as well as other aspects of the B4C optical coatings and surfaces before and after the plasma cleaning process are reported.

  20. Resonant soft x-ray reflectivity of Me/B(4)C multilayers near the boron K edge.

    Science.gov (United States)

    Ksenzov, Dmitriy; Schlemper, Christoph; Pietsch, Ullrich

    2010-09-01

    Energy dependence of the optical constants of boron carbide in the short period Ru/B(4)C and Mo/B(4)C multilayers (MLs) are evaluated from complete reflectivity scans across the boron K edge using the energy-resolved photon-in-photon-out method. Differences between the refractive indices of the B(4)Cmaterial inside and close to the surface are obtained from the peak profile of the first order ML Bragg peak and the reflection profile near the critical angle of total external reflection close to the surface. Where a Mo/B(4)C ML with narrow barrier layers appears as a homogeneous ML at all energies, a Ru/B(4)C ML exhibits another chemical nature of boron at the surface compared to the bulk. From evaluation of the critical angle of total external reflection in the energy range between 184 and 186eV, we found an enriched concentration of metallic boron inside the Ru-rich layer at the surface, which is not visible in other energy ranges.

  1. The CHRNA5-A3-B4 Gene Cluster and Smoking: From Discovery to Therapeutics.

    Science.gov (United States)

    Lassi, Glenda; Taylor, Amy E; Timpson, Nicholas J; Kenny, Paul J; Mather, Robert J; Eisen, Tim; Munafò, Marcus R

    2016-12-01

    Genome-wide association studies (GWASs) have identified associations between the CHRNA5-CHRNA3-CHRNB4 gene cluster and smoking heaviness and nicotine dependence. Studies in rodents have described the anatomical localisation and function of the nicotinic acetylcholine receptors (nAChRs) formed by the subunits encoded by this gene cluster. Further investigations that complemented these studies highlighted the variability of individuals' smoking behaviours and their ability to adjust nicotine intake. GWASs of smoking-related health outcomes have also identified this signal in the CHRNA5-CHRNA3-CHRNB4 gene cluster. This insight underpins approaches to strengthen causal inference in observational data. Combining genetic and mechanistic studies of nicotine dependence and smoking heaviness may reveal novel targets for medication development. Validated targets can inform genetic therapeutic interventions for smoking cessation and tobacco-related diseases. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Recruitment of activation receptors at inhibitory NK cell immune synapses.

    Directory of Open Access Journals (Sweden)

    Nicolas Schleinitz

    2008-09-01

    Full Text Available Natural killer (NK cell activation receptors accumulate by an actin-dependent process at cytotoxic immune synapses where they provide synergistic signals that trigger NK cell effector functions. In contrast, NK cell inhibitory receptors, including members of the MHC class I-specific killer cell Ig-like receptor (KIR family, accumulate at inhibitory immune synapses, block actin dynamics, and prevent actin-dependent phosphorylation of activation receptors. Therefore, one would predict inhibition of actin-dependent accumulation of activation receptors when inhibitory receptors are engaged. By confocal imaging of primary human NK cells in contact with target cells expressing physiological ligands of NK cell receptors, we show here that this prediction is incorrect. Target cells included a human cell line and transfected Drosophila insect cells that expressed ligands of NK cell activation receptors in combination with an MHC class I ligand of inhibitory KIR. The two NK cell activation receptors CD2 and 2B4 accumulated and co-localized with KIR at inhibitory immune synapses. In fact, KIR promoted CD2 and 2B4 clustering, as CD2 and 2B4 accumulated more efficiently at inhibitory synapses. In contrast, accumulation of KIR and of activation receptors at inhibitory synapses correlated with reduced density of the integrin LFA-1. These results imply that inhibitory KIR does not prevent CD2 and 2B4 signaling by blocking their accumulation at NK cell immune synapses, but by blocking their ability to signal within inhibitory synapses.

  3. Coatings for FEL optics: preparation and characterization of B4C and Pt.

    Science.gov (United States)

    Störmer, Michael; Siewert, Frank; Horstmann, Christian; Buchheim, Jana; Gwalt, Grzegorz

    2018-01-01

    Large X-ray mirrors are required for beam transport at both present-day and future free-electron lasers (FELs) and synchrotron sources worldwide. The demand for large mirrors with lengths up to 1 m single layers consisting of light or heavy elements has increased during the last few decades. Accordingly, surface finishing technology is now able to produce large substrate lengths with micro-roughness on the sub-nanometer scale. At the Helmholtz-Zentrum Geesthacht (HZG), a 4.5 m-long sputtering facility enables us to deposit a desired single-layer material some tens of nanometers thick. For the European XFEL project, the shape error should be less than 2 nm over the whole 1 m X-ray mirror length to ensure the safe and efficient delivery of X-ray beams to the scientific instruments. The challenge is to achieve thin-film deposition on silicon substrates, benders and gratings without any change in mirror shape. Thin films of boron carbide and platinum with a thickness in the range 30-100 nm were manufactured using the HZG sputtering facility. This setup is able to cover areas of up to 1500 mm × 120 mm in one step using rectangular sputtering sources. The coatings produced were characterized using various thin-film methods. It was possible to improve the coating process to achieve a very high uniformity of the layer thickness. The movement of the substrate in front of the sputtering source has been optimized. A variation in B 4 C layer thickness below 1 nm (peak-to-valley) was achieved at a mean thickness of 51.8 nm over a deposition length of 1.5 m. In the case of Pt, reflectometry and micro-roughness measurements were performed. The uniformity in layer thickness was about 1 nm (peak-to-valley). The micro-roughness of the Pt layers showed no significant change in the coated state for layer thicknesses of 32 nm and 102 nm compared with the uncoated substrate state. The experimental results achieved will be discussed with regard to current

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

    Directory of Open Access Journals (Sweden)

    Przemysław Rzodkiewicz

    2016-10-01

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

  5. Mechanical and Micro structural Characterization of Al-Al/B4C Laminated Composites Depending on Manufacturing Parameters

    Science.gov (United States)

    Göçer, A.; Nair, F.; Karamış, M. B.

    2018-01-01

    In this study, it is aimed to produce a layered composite structure with Al sheath and Al / B4C cored by extrusion technique and to characterize the mechanical and micro structure of the products. In the production of composite billets, powder in tube (PIT) method was used. In this method, Al7075 (ø 30 mm) tube is filled with Al2124 / B4C powder mixtures. The semi-finished composite billets were sintered at 500 ° C for 1 hour and extruded at the extrusion ratios of R = 14 R = 9 and R = 6.25 at the same temperature to obtain circular cross-section rods. The density changes, hardness distributions and sheath-core section ratios of these bars were determined. The changes of these values depending on the extrusion rate and B4C ratio were investigated. It is also revealed in the micro structure changes depending on these ratios.

  6. Optimization of Squeeze Casting Process Parameters Using Taguchi in LM13 Matrix B4C Reinforced Composites

    Science.gov (United States)

    Akhil, K. T.; Arul, Sanjivi

    2018-02-01

    Aluminium metal matrix composite has widely used in aerospace and automobile industry due to its high strength to weight ratio. Aluminium LM13 matrix B4C reinforced composites are mainly manufactured by Squeeze casting process. The present work optimizes squeeze casting process parameters using Taguchi method. The control factors used for the experiments were Squeeze Pressure, Die Preheat Temperature and weight percentage of Boron Carbide (B4C) along with multiple performance characteristic of Hardness, Ultimate Tensile Strength (UTS) and Yield Strength (YS). The L27 orthogonal array was used for experimental design. Analysis of variance (ANOVA) is used to determine the significant factor and found out that Squeeze pressure is the most significant factor followed by percentage of B4C.

  7. Development of Mg B4 O7:Dy thermoluminescent solid dosemeter for using on the thermal neutron dosimetry

    International Nuclear Information System (INIS)

    Potiens Junior, A.J.; Campos, L.L.; Todo, A.S.

    1992-01-01

    The magnesium tetraborate doped with dysprosium (Mg B 4 O 7 :O y ) thermoluminescent phosphor is developed, containing boron, which boron 10 isotope has high cross section for thermal neutrons by 10 B (n,α) 7 Li reaction. The nitric acid concentration, the number of washing for removing the excess of boric acid, the powder granulation of Mg B 4 O 7 :O y , the percentage of teflon used as binder and the reproducibility of thermoluminescent answer are also presented. (C.G.C.)

  8. Thermal transformation of synthetic borax, Na2[B4O5(OH)4]x8H2O

    International Nuclear Information System (INIS)

    Abdullaev, G.K.

    1981-01-01

    Using the methods of high temperature roentgenography and derivatography thermal transformation of synthetic borax is studied. It is established that borax dehydration proceeds in four stages (50-80, 80-100, 100-150 and 150-500 deg C) with the formation of three intermediate crystalline hydrate forms (one stable and two unstable) and one final stable crystalline phase. The stable crystalline phases correspond to synthetic tincalconite Na 2 [B 4 O 5 (OH) 4 ]x3H 2 O and sodium tetraborate Na 2 B 4 O 7 . Thermal transformation of borax into tincalconite and sodium tetraborate is explained on the basis of their crystal structures [ru

  9. 2B4-SAP signaling is required for the priming of naive CD8+T cells by antigen-expressing B cells and B lymphoma cells.

    Science.gov (United States)

    Huang, Yu-Hsuan; Tsai, Kevin; Tan, Sara Y; Kang, Sohyeong; Ford, Mandy L; Harder, Kenneth W; Priatel, John J

    2017-01-01

    Mutations in SH2D1A gene that encodes SAP (SLAM-associated protein) result in X-linked lymphoproliferative disease (XLP), a rare primary immunodeficiency disease defined by exquisite sensitivity to the B-lymphotropic Epstein-Barr virus (EBV) and B cell lymphomas. However, the precise mechanism of how the loss of SAP function contributes to extreme vulnerability to EBV and the development of B cell lymphomas remains unclear. Here, we investigate the hypothesis that SAP is critical for CD8 + T cell immune surveillance of antigen (Ag)-expressing B cells or B lymphoma cells under conditions of defined T cell receptor (TCR) signaling. Sh2d1a - / - CD8 + T cells exhibited greatly diminished proliferation relative to wild type when Ag-presenting-B cells or -B lymphoma cells served as the primary Ag-presenting cell (APC). By contrast, Sh2d1a - / - CD8 + T cells responded equivalently to wild-type CD8 + T cells when B cell-depleted splenocytes, melanoma cells or breast carcinoma cells performed Ag presentation. Through application of signaling lymphocyte activation molecule (SLAM) family receptor blocking antibodies or SLAM family receptor-deficient CD8 + T cells and APCs, we found that CD48 engagement on the B cell surface by 2B4 is crucial for initiating SAP-dependent signaling required for the Ag-driven CD8 + T cell proliferation and differentiation. Altogether, a pivotal role for SAP in promoting the expansion and differentiation of B cell-primed viral-specific naive CD8 + T cells may explain the selective immune deficiency of XLP patients to EBV and B cell lymphomas.

  10. Resolvin D1 limits 5-lipoxygenase nuclear localization and leukotriene B4 synthesis by inhibiting a calcium-activated kinase pathway.

    Science.gov (United States)

    Fredman, Gabrielle; Ozcan, Lale; Spolitu, Stefano; Hellmann, Jason; Spite, Matthew; Backs, Johannes; Tabas, Ira

    2014-10-07

    Imbalances between proinflammatory and proresolving mediators can lead to chronic inflammatory diseases. The balance of arachidonic acid-derived mediators in leukocytes is thought to be achieved through intracellular localization of 5-lipoxygenase (5-LOX): nuclear 5-LOX favors the biosynthesis of proinflammatory leukotriene B4 (LTB4), whereas, in theory, cytoplasmic 5-LOX could favor the biosynthesis of proresolving lipoxin A4 (LXA4). This balance is shifted in favor of LXA4 by resolvin D1 (RvD1), a specialized proresolving mediator derived from docosahexaenoic acid, but the mechanism is not known. Here we report a new pathway through which RvD1 promotes nuclear exclusion of 5-LOX and thereby suppresses LTB4 and enhances LXA4 in macrophages. RvD1, by activating its receptor formyl peptide receptor2/lipoxin A4 receptor, suppresses cytosolic calcium and decreases activation of the calcium-sensitive kinase calcium-calmodulin-dependent protein kinase II (CaMKII). CaMKII inhibition suppresses activation P38 and mitogen-activated protein kinase-activated protein kinase 2 kinases, which reduces Ser271 phosphorylation of 5-LOX and shifts 5-LOX from the nucleus to the cytoplasm. As such, RvD1's ability to decrease nuclear 5-LOX and the LTB4:LXA4 ratio in vitro and in vivo was mimicked by macrophages lacking CaMKII or expressing S271A-5-LOX. These findings provide mechanistic insight into how a specialized proresolving mediator from the docosahexaenoic acid pathway shifts the balance toward resolution in the arachidonic acid pathway. Knowledge of this mechanism may provide new strategies for promoting inflammation resolution in chronic inflammatory diseases.

  11. Peculiar features of metallurgical processes at plasma-arc spraying of coatings, made of steel wire with powder fillers B4C and B4C+ZrO2

    Directory of Open Access Journals (Sweden)

    Георгій Михайлович Григоренко

    2016-11-01

    Full Text Available The interaction of metallurgical processes occurring in plasma-arc spraying between the steel shell and the carbide fillers of B4C and B4C cored wires with the addition of nanocrystalline ZrO2 powder has been analyzed. Iron-boron compounds alloyed with carbon are formed in ingots as a result of ferritiс coating of wire interacrion with fillers while the ferritic matrix contains boride and carboboride eutectics. Average microhardness of the carboboride compounds and the matrix is high – 17,78; 16,40 and 8,69; 9,95 GPa for the ingots with с B4C and B4C+ZrO2 respectively. The best quality coatings with low porosity (~1%, lamellar structure consisting of ferrite matrix reinforced with dispersed Fe borides, were obtained at a higher heat input (plasmatron current 240-250 A. The average amount of oxides in the coatings makes 15%. 0,5% addition of nanopowder ZrO2 accelerates dispersed iron-boron compounds forming, promotes their uniform distribution in the structure and improves coating microhardness up to 7,0 GPa. Application of the differential thermal analysis method to simulate the interaction processes between the steel shell and the filler during the heating of wire in the shielding gas makes it possible to promote formation of new phases (borides and carboborides of iron and to predict the phase composition of the coatings

  12. Nido-Carborane building-block reagents. 2. Bulky-substituent (alkyl)2C2B4H6 derivatives and (C6H5)2C2B4H6: synthesis and properties

    International Nuclear Information System (INIS)

    Boyter, H.A. Jr.; Grimes, R.N.

    1988-01-01

    The preparation and chemistry of nido-2,3-R 2 C 2 C 2 B 4 H 6 carboranes in which R is n-butyl, isopentyl, n-hexyl, and phenyl was investigated in order to further assess the steric and electronic influence of the R groups on the properties of the nido-C 2 B 4 cage, especially with respect to metal complexation at the C 2 B 3 face and metal-promoted oxidative fusion. The three dialkyl derivatives were prepared from the corresponding dialkylacetylenes via reaction with B 5 H 9 and triethylamine, but the diphenyl compound could not be prepared in this manner and was obtained instead in a thermal reaction of B 5 H 9 with diphenylacetylene in the absence of amine. All four carboranes are readily bridge-deprotonated by NaH in THF, and the anions of the dialkyl species, on treatment with FeCl 2 and air oxidation, generate the respective R 4 C 4 B 8 H 8 carborane fusion products were R = n-C 4 H 9 , i-C 5 H 11 or n-C 6 H 13 . The diphenylcarborane anion Ph 2 C 2 B 4 H 5 - did not form detectable metal complexes with Fe 2+ , Co 2+ , or Ni 2+ , and no evidence of a Ph 4 C 4 B 8 H 8 fusion product has been found. Treatment of Ph 2 C 2 B 4 H 6 with Cr(CO) 6 did not lead to metal coordination of the phenyl rings, unlike (PhCH 2 ) 2 C 2 B 4 H 6 , which had previously been shown to form mono- and bis(tricarbonylchromium) complexes. However, the reaction of Ph 2 C 2 B 4 H 5 - , CoCl 2 , and (PhPCH 2 ) 2 did give 1,1-(Ph 2 PCH 2 ) 2 -1-Cl-1,2,3-Co(Ph 2 C 2 B 4 H 4 ), the only case in which metal complexation of the diphenylcarborane was observed. 14 references, 3 figures, 3 tables

  13. 7 CFR Exhibit B-4 to Subpart B of... - Letter for Notifying Applicants, Lenders and Holders and Borrowers of Unfavorable Decision...

    Science.gov (United States)

    2010-01-01

    ... Used in Cases Involving Farmer Program Primary Loan Servicing Actions) B Exhibit B-4 to Subpart B of... AGRICULTURE PROGRAM REGULATIONS GENERAL Adverse Decisions and Administrative Appeals Pt. 1900, Subpt. B, Exh. B-4 Exhibit B-4 to Subpart B of Part 1900—Letter for Notifying Applicants, Lenders and Holders and...

  14. 76 FR 20506 - Technical Amendment to Rule 19b-4: Filings With Respect to Proposed Rule Changes by Self...

    Science.gov (United States)

    2011-04-13

    ... anticipate that any competitive advantages or disadvantages would be created. List of Subjects in 17 CFR Part... that references to ``business day'' in Section 19(b) of the Exchange Act and Rule 19b-4 thereunder... business. DATES: Effective Date: April 13, 2011. FOR FURTHER INFORMATION CONTACT: Richard Holley III...

  15. 26 CFR 1.367(b)-4 - Acquisition of foreign corporate stock or assets by a foreign corporation in certain...

    Science.gov (United States)

    2010-04-01

    ...) and any regulations thereunder. If any of the assets transferred are intangible assets, see section... 26 Internal Revenue 4 2010-04-01 2010-04-01 false Acquisition of foreign corporate stock or assets...) INCOME TAXES Effects on Corporation § 1.367(b)-4 Acquisition of foreign corporate stock or assets by a...

  16. 29 CFR 2550.408b-4 - Statutory exemption for investments in deposits of banks or similar financial institutions.

    Science.gov (United States)

    2010-07-01

    ....408b-4 Statutory exemption for investments in deposits of banks or similar financial institutions. (a... financial institution may make investments in deposits which bear a reasonable rate of interest in itself... 29 Labor 9 2010-07-01 2010-07-01 false Statutory exemption for investments in deposits of banks or...

  17. Insulin receptors

    International Nuclear Information System (INIS)

    Kahn, C.R.; Harrison, L.C.

    1988-01-01

    This book contains the proceedings on insulin receptors. Part A: Methods for the study of structure and function. Topics covered include: Method for purification and labeling of insulin receptors, the insulin receptor kinase, and insulin receptors on special tissues

  18. Electron energy-loss and soft X-ray emission spectroscopy of electronic structure of MgB4

    Science.gov (United States)

    Sato, Yohei; Saito, Taiki; Tsuchiya, Kohei; Terauchi, Masami; Saito, Hiroki; Takeda, Masatoshi

    2017-09-01

    The electronic structure of MgB4, with the characteristic crystal structure comprising one-dimensional pentagonal B6 cluster chain, was investigated using electron energy-loss spectroscopy and soft X-ray emission spectroscopy based on transmission electron microscopy. The dielectric function and density of state of unoccupied and occupied states were clarified experimentally for the first time. Although theoretical calculations has predicted MgB4 to be a semiconductor, the electron energy-loss spectrum in this study show a plasmon peak at 0.4 eV, which might be due to carrier electrons. Theoretical calculations suggested that the electronic states near the Fermi energy are localized along the one dimensional B6 cluster chain. Therefore, one-dimensional electric conductivity is expected.

  19. Transmission electron microscope studies of the chromium cast iron modified at use of B4C addition

    Directory of Open Access Journals (Sweden)

    K. Labisz

    2010-10-01

    Full Text Available Results of studies of the high alloy chromium cast iron with boron addition in form of the B4C phase powder are presented in this paper.The main field of interest is the identification of phases based on the transmission electron microscope study, occurred in this alloy aftersolidification process. The structure mainly consists of the austenite matrix and M7C3 carbide identified as the Cr7C3 phase.

  20. Epizootic of vesicular disease in pigs caused by coxsackievirus B4 in the Soviet Union in 1975.

    Science.gov (United States)

    Lomakina, Natalia F; Shustova, Elena; Strizhakova, Olga M; Drexler, Felix; Lukashev, Alexander N

    2016-01-01

    Swine vesicular disease virus (SVDV) emerged around 1960 from a human enterovirus ancestor, coxsackievirus B5 (CVB5), and caused a series of epizootics in Europe and Asia. We characterized a coxsackievirus B4 strain that caused an epizootic involving 24 488 pigs in the Soviet Union in 1975. Phylogenetic evidence suggested that the swine virus emerged from a human ancestor between 1945 and 1975, almost simultaneously with the transfer of CVB5.

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

    Science.gov (United States)

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

    2015-02-01

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

  2. Enhancement of thermal neutron attenuation of nano-B4C, -BN dispersed neutron shielding polymer nanocomposites

    International Nuclear Information System (INIS)

    Kim, Jaewoo; Lee, Byung-Chul; Uhm, Young Rang; Miller, William H.

    2014-01-01

    Highlights: • Preparation of B 4 C and BN nanopowders using a simple ball milling process. • Homogeneous dispersion and strong adhesion of nano-B 4 C and -BN with polymer matrix. • Enhancement of mechanical properties of the nanocomposites compared to their micro counterparts. • Enhancement of thermal neutron attenuation of the nanocomposites. - Abstract: Nano-sized boron carbide (B 4 C) and boron nitride (BN) powder were prepared using ball milling. Micro- and milled nano-powders were melt blended with high density polyethylene (HDPE) using a polymer mixer followed by hot pressing to fabricate sheet composites. The tensile and flexural strengths of HDPE nanocomposites were ∼20% higher than their micro counterparts, while those for latter decreased compared to neat HDPE. Thermal neutrons attenuation of the prepared HDPE nanocomposites was evaluated using a monochromatic ∼0.025 eV neutron beam. Thermal neutron attenuation of the HDPE nanocomposites was greatly enhanced compared to their micro counterparts at the same B-10 areal densities. Monte Carlo n-Particles (MCNP) simulations based on the lattice structure modeling also shows the similar filler size dependent thermal neutron absorption

  3. SERPINB3/B4 contributes to early inflammation and barrier dysfunction in an experimental murine model of atopic dermatitis.

    Science.gov (United States)

    Sivaprasad, Umasundari; Kinker, Kayla G; Ericksen, Mark B; Lindsey, Mark; Gibson, Aaron M; Bass, Stacey A; Hershey, Nicolas S; Deng, Jingyuan; Medvedovic, Mario; Khurana Hershey, Gurjit K

    2015-01-01

    Serine proteases are critical for epidermal barrier homeostasis, and their aberrant expression and/or activity is associated with chronic skin diseases. Elevated levels of the serine protease inhibitors SERPINB3 and SERPINB4 are seen in patients with atopic dermatitis and psoriasis. However, their mechanistic role in the skin is unknown. To evaluate the contribution of Serpinb3a (mouse homolog of SERPINB3 and SERPINB4) in atopic dermatitis, we examined the effect of topical Aspergillus fumigatus extract exposure in wild-type and Serpinb3a-null mice on transepidermal water loss (TEWL), sensitization, and inflammation. Allergen exposure induced Serpinb3a expression in the skin, along with increased TEWL, epidermal thickness, and skin inflammation, all of which were attenuated in the absence of Serpinb3a. Attenuated TEWL correlated with decreased expression of the pro-inflammatory marker S100A8. Silencing of SERPINB3/B4 in human keratinocytes decreased S100A8 expression, supporting a role for SERPINB3/B4 in the initiation of the acute inflammatory response. RNA-seq analysis following allergen exposure identified a network of pro-inflammatory genes induced in wild-type mice that was absent in Serpinb3a-null mice. In conclusion, Serpinb3a deficiency attenuates barrier dysfunction and the early inflammatory response following cutaneous allergen exposure, supporting a role for Serpinb3a (mice) and SERPINB3/B4 (humans) early in atopic dermatitis.

  4. PRESSURELESS SINTERING OF B4C-NANOTiB2 NANOCOMPOSITE BY ADDITION OF Fe AND Ni AS SINTERING AIDS

    Directory of Open Access Journals (Sweden)

    M. M. Mohammadi Samani

    2014-12-01

    Full Text Available B4C and its composites with TiB2 as second phase continues to be extensively used as the preferred ceramic material in military applications as armor systems for absorbing and dissipating kinetic energy from high velocity projectiles. It also exhibits a high melting point (2427 °C, and high neutron absorption cross section. Pressureless sintering of the B 4C-nanoTiB2 nanocomposite using small amount of Fe and Ni (≤3 Wt% as sintering aids was investigated in order to clarify the role of Fe and Ni additions on the mechanical and microstructural properties of B4C-nanoTiB2 nanocomposites. Different amount of Fe and Ni, mainly 1 to 3 Wt% were added to the base material. Pressureless sintering was conducted at 2175, 2225 and 2300 °C. It was found that Addition of 3 Wt% Fe and 3 wt% Ni and sintering at 2300 °C resulted in improving the density of the samples to about 99% of theoretical density. The nanocomposite samples exhibited high density, hardness, and microstructural uniformity.

  5. In Situ Preparation and Thermoelectric Properties of B4C1- x -TiB2 Composites

    Science.gov (United States)

    Feng, Bing; Martin, Hans-Peter; Michaelis, Alexander

    2013-07-01

    B4C1- x -TiB2 composites were prepared by in situ reactive spark plasma sintering of B4C with addition of nano-TiO2 powder. The effect of TiO2 addition on the sinterability of boron carbide was studied. The composition and the microstructure of the dense composites are characterized by means of x-ray diffraction (XRD), scanning electron microscopy (SEM), and energy-dispersive x-ray spectroscopy (EDX). The studies show that the composites contain boron carbide and TiB2 phases with a homogeneous structure. In addition, the correlation between the composition and the thermoelectric properties was investigated. The electrical conductivity of the composite increased with increasing addition of TiO2, and the Seebeck coefficient decreased with TiO2 addition. The percolation threshold ø c for TiB2 in the B4C1- x -TiB2 system was found to be in the range of 0.139 to 0.189. The thermal conductivity was reduced in the whole measuring temperature range from 50°C to 800°C below ø c. Accordingly, a significant enhancement in the dimensionless figure of merit ZT of the composites was achieved compared with that of boron carbide without TiO2 addition, with ZT achieving its maximum value at 10 wt.% TiO2.

  6. Lipoxin A4 and lipoxin B4 stimulate the release but not the oxygenation of arachidonic acid in human neutrophils: Dissociation between lipid remodeling and adhesion

    Energy Technology Data Exchange (ETDEWEB)

    Nigam, S.; Fiore, S.; Luscinskas, F.W.; Serhan, C.N. (Brigham and Women' s Hospital, Boston, MA (USA))

    1990-06-01

    The profiles of actions of lipoxin A4 (LXA4) and lipoxin B4 (LXB4), two lipoxygenase-derived eicosanoids, were examined with human neutrophils. At nanomolar concentrations, LXA4 and LXB4 each stimulated the release of (1-14C)arachidonic acid from esterified sources in neutrophils. Lipoxin-induced release of (1-14C)arachidonic acid was both dose- and time-dependent and was comparable to that induced by the chemotactic peptide f-met-leu-phe. Time-course studies revealed that lipoxin A4 and lipoxin B4 each induced a biphasic release of (1-14C)arachidonic acid, which was evident within seconds (5-15 sec) in its initial phase and minutes (greater than 30 sec) in the second phase. In contrast, the all-trans isomers of LXA4 and LXB4 did not provoke (1-14C)AA release. Lipoxin-induced release of arachidonic acid was inhibited by prior treatment of the cells with pertussis toxin but not by its beta-oligomers, suggesting the involvement of guaninine nucleotide-binding regulatory proteins in this event. Dual radiolabeling of neutrophil phospholipid classes with (1-14C)arachidonic acid and (3H)palmitic acid showed that phosphatidylcholine was a major source of lipoxin-induced release of (1-14C)arachidonic acid. They also demonstrated that lipoxins rapidly stimulate both formation of phosphatidic acid as well as phospholipid remodeling. Although both LXA4 and LXB4 (10(-8)-10(-6) M) stimulated the release of (1-14C)arachidonic acid, neither compound evoked its oxygenation by either the 5- or 15-lipoxygenase pathways (including the formation of LTB4, 20-COOH-LTB4, 5-HETE, or 15-HETE). LXA4 and LXB4 (10(-7) M) each stimulated the elevation of cytosolic Ca2+ as monitored with Fura 2-loaded cells, albeit to a lesser extent than equimolar concentrations of FMLP. Neither lipoxin altered the binding of (3H)LTB4 to its receptor on neutrophils.

  7. Formation of silver nanoparticles in Li2B4O7-Ag2O and Li2B4O7-Gd2O3-Ag2O borate glasses.

    Science.gov (United States)

    Adamiv, Volodymyr; Gamernyk, Roman; Teslyuk, Ihor

    2017-06-10

    Results of investigations of 98.0Li 2 B 4 O 7 -2.0Ag 2 O and 97.0Li 2 B 4 O 7 -2.0Ag 2 O-1.0Gd 2 O 3 glasses with Ag nanoparticles (Ag NPs), formed by thermal treatment in vacuum and in air, are presented. Intensive plasmon absorption bands, connected with Ag NPs, were observed in their optical transmission spectra. It is ascertained that in volumes of both glasses there is formed a small number of Ag NPs, whereas their main mass is concentrated near the surface of samples. The mechanism of Ag NPs formation is proposed. A conclusion is drawn that annealing in vacuum does not necessarily require the presence of reducing ions, whereas formation of nanoparticles at annealing in air is impossible without reducing agents. Structural defects play a decisive role in the Ag NPs nucleation process. Radii of formed Ag NPs are estimated by the half-width of plasmon bands, and by means of small-angle x-ray scattering.

  8. Radioimmunological detection of type-specific antibodies against polioviruses 1, 2 and 3 as well as the B4 Coxsackie virus. Radioimmunologischer Nachweis typenspezifischer Antikoerper gegen Poliovirus 1, 2 und 3 und gegen Coxsackievirus B4

    Energy Technology Data Exchange (ETDEWEB)

    Hartung Goetze, C.F.

    1985-06-27

    A simple radioimmunological procedure is described in which the qualitative and quantitative determination of serum antibodies against polioviruses 1, 2 and 3 and against the B4 Coxsackie virus is based on adsorption chromatography. It is comparable to the neutralisation test as regards sensitivity and specifity and has the additional advantage of being the faster, simplier and cheaper of those two methods. The radioactive labelling of the virsuses was achieved with types of 32 P or 3 H that had favourable half-lives and would thus permit the labelled compounds to be stored for prolonged periods of time. The immunological statuses and antibody titres of sera obtained from 45 female volunteers, where the vaccinations against polymyelitis had mostly been carried out by the oral route, showed remarkably little changes, which was evident from the fact that the proportion of study participants found to have antibodies against all three serological types was 91% in 1970 and still as large at 89% in 1983. When a total of 1016 sera were screened for Coxsackie virus B4, no age dependency could be determined for the age range between 5 and 35 years, nor were there any differences seen between the individual residential areas. (TRV).

  9. Deposition and characterization of B4C/CeO2 multilayers at 6.x nm extreme ultraviolet wavelengths

    Science.gov (United States)

    Sertsu, M. G.; Giglia, A.; Brose, S.; Park, D.; Wang, Z. S.; Mayer, J.; Juschkin, L.; Nicolosi, P.

    2016-03-01

    New multilayers of boron carbide/cerium dioxide (B4C/CeO2) combination on silicon (Si) substrate are manufactured to represent reflective-optics candidates for future lithography at 6.x nm wavelength. This is one of only a few attempts to make multilayers of this kind. Combination of several innovative experiments enables detailed study of optical properties, structural properties, and interface profiles of the multilayers in order to open up a room for further optimization of the manufacturing process. The interface profile is visualized by high-angle annular dark-field imaging which provides highly sensitive contrast to atomic number. Synchrotron based at-wavelength extreme ultraviolet (EUV) reflectance measurements near the boron (B) absorption edge allow derivation of optical parameters with high sensitivity to local atom interactions. X-ray reflectivity measurements at Cu-Kalpha (8 keV ) determine the period of multilayers with high in-depth resolution. By combining these measurements and choosing robust nonlinear curve fitting algorithms, accuracy of the results has been significantly improved. It also enables a comprehensive characterization of multilayers. Interface diffusion is determined to be a major cause for the low reflectivity performance. Optical constants of B4C and CeO2 layers are derived in EUV wavelengths. Besides, optical properties and asymmetric thicknesses of inter-diffusion layers (interlayers) in EUV wavelengths near the boron edge are determined. Finally, ideal reflectivity of the B4C/CeO2 combination is calculated by using optical constants derived from the proposed measurements in order to evaluate the potentiality of the design.

  10. Atomic structure of icosahedral B4C boron carbide from a first principles analysis of NMR spectra.

    Science.gov (United States)

    Mauri, F; Vast, N; Pickard, C J

    2001-08-20

    Density functional theory is demonstrated to reproduce the 13C and 11B NMR chemical shifts of icosahedral boron carbides with sufficient accuracy to extract previously unresolved structural information from experimental NMR spectra. B4C can be viewed as an arrangement of 3-atom linear chains and 12-atom icosahedra. According to our results, all the chains have a CBC structure. Most of the icosahedra have a B11C structure with the C atom placed in a polar site, and a few percent have a B (12) structure or a B10C2 structure with the two C atoms placed in two antipodal polar sites.

  11. Dwarfism with joint laxity in Friesian horses is associated with a splice site mutation in B4GALT7.

    Science.gov (United States)

    Leegwater, Peter A; Vos-Loohuis, Manon; Ducro, Bart J; Boegheim, Iris J; van Steenbeek, Frank G; Nijman, Isaac J; Monroe, Glen R; Bastiaansen, John W M; Dibbits, Bert W; van de Goor, Leanne H; Hellinga, Ids; Back, Willem; Schurink, Anouk

    2016-10-28

    Inbreeding and population bottlenecks in the ancestry of Friesian horses has led to health issues such as dwarfism. The limbs of dwarfs are short and the ribs are protruding inwards at the costochondral junction, while the head and back appear normal. A striking feature of the condition is the flexor tendon laxity that leads to hyperextension of the fetlock joints. The growth plates of dwarfs display disorganized and thickened chondrocyte columns. The aim of this study was to identify the gene defect that causes the recessively inherited trait in Friesian horses to understand the disease process at the molecular level. We have localized the genetic cause of the dwarfism phenotype by a genome wide approach to a 3 Mb region on the p-arm of equine chromosome 14. The DNA of two dwarfs and one control Friesian horse was sequenced completely and we identified the missense mutation ECA14:g.4535550C > T that cosegregated with the phenotype in all Friesians analyzed. The mutation leads to the amino acid substitution p.(Arg17Lys) of xylosylprotein beta 1,4-galactosyltransferase 7 encoded by B4GALT7. The protein is one of the enzymes that synthesize the tetrasaccharide linker between protein and glycosaminoglycan moieties of proteoglycans of the extracellular matrix. The mutation not only affects a conserved arginine codon but also the last nucleotide of the first exon of the gene and we show that it impedes splicing of the primary transcript in cultured fibroblasts from a heterozygous horse. As a result, the level of B4GALT7 mRNA in fibroblasts from a dwarf is only 2 % compared to normal levels. Mutations in B4GALT7 in humans are associated with Ehlers-Danlos syndrome progeroid type 1 and Larsen of Reunion Island syndrome. Growth retardation and ligamentous laxity are common manifestations of these syndromes. We suggest that the identified mutation of equine B4GALT7 leads to the typical dwarfism phenotype in Friesian horses due to deficient splicing of transcripts of

  12. Operation of the CESR-TA vertical beam size monitor at $E_{\\rm b}$=4 GeV

    OpenAIRE

    Alexander, J. P.; Conolly, C.; Edwards, E.; Flanagan, J. W.; Fontes, E.; Heltsley, B. K.; Lyndaker, A.; Peterson, D. P.; Rider, N. T.; Rubin, D. L.; Seeley, R.; Shanks, J.

    2015-01-01

    We describe operation of the CESR-TA vertical beam size monitor (xBSM) with $e^\\pm$ beams with $E_{\\rm b}$=4 GeV. The xBSM measures vertical beam size by imaging synchrotron radiation x-rays through an optical element onto a detector array of 32 InGaAs photodiodes with 50 $\\mu$m pitch. The device has previously been successfully used to measure vertical beam sizes of 10-100 $\\mu$m on a bunch-by-bunch, turn-by-turn basis at $e^\\pm$ beam energies of $\\sim$2 GeV and source magnetic fields below ...

  13. Fabrication of Al5083/B4C surface composite by friction stir processing and its tribological characterization

    Directory of Open Access Journals (Sweden)

    Narayana Yuvaraj

    2015-10-01

    Full Text Available Improved surface properties with the retainment of bulk properties are necessary for a component for enhanced wear characteristics. Friction stir processing (FSP is used to produce such surface composites. Fabrication of 5083 aluminum alloy with reinforced layers of boron carbide (B4C through FSP was carried out. Micro and nano sized B4C particles were used as reinforcements. The friction processed surface composite layer was analyzed through optical and scanning electron microscopical studies. The number of passes and the size of reinforcement play a vital role in the development of surface composites by FSP. Mechanical properties of the friction stir processed surface composites were evaluated through micro hardness and universal tensile tests. The results were compared with the properties of the base metal. The role of reinforcement and number of passes on properties were also evaluated. Tribological performance of the surface composites is tested through pin on disk test. The surface composite layer resulted in three passes with nano particle reinforcement exhibited better properties in hardness, tensile behavior and wear resistance compared to the behavior of the base metal.

  14. High-pressure phase transition makes B4.3C boron carbide a wide-gap semiconductor.

    Science.gov (United States)

    Hushur, Anwar; Manghnani, Murli H; Werheit, Helmut; Dera, Przemyslaw; Williams, Quentin

    2016-02-03

    Single-crystal B4.3C boron carbide is investigated through the pressure-dependence and inter-relation of atomic distances, optical properties and Raman-active phonons up to ~70 GPa. The anomalous pressure evolution of the gap width to higher energies is striking. This is obtained from observations of transparency, which most rapidly increases around 55 GPa. Full visible optical transparency is approached at pressures of  >60 GPa indicating that the band gap reaches ~3.5 eV; at high pressure, boron carbide is a wide-gap semiconductor. The reason is that the high concentration of structural defects controlling the electronic properties of boron carbide at ambient conditions initially decreases and finally vanishes at high pressures. The structural parameters and Raman-active phonons indicate a pressure-dependent phase transition in single-crystal (nat)B4.3C boron carbide near 40 GPa, likely related to structural changes in the C-B-C chains, while the basic icosahedral structure appears to be less affected.

  15. Influence of growth medium on cometabolic degradation of polycyclic aromatic hydrocarbons by Sphingomonas sp. strain PheB4

    Energy Technology Data Exchange (ETDEWEB)

    Zhong Yin; Wang Xiaowei [Sun Yat-Sen Univ., Guangzhou (China). State Key Lab. of Biocontrol; Futian-CityU Mangrove Research and Development Centre, Shenzhen (China). Futian National Nature Reserve; Luan Tiangang; Lan Chongyu [Sun Yat-Sen Univ., Guangzhou (China). State Key Lab. of Biocontrol; Tam, N.F.Y. [Futian-CityU Mangrove Research and Development Centre, Shenzhen (China). Futian National Nature Reserve; City Univ. of Hong Kong, Kowloon (China). Dept. of Biology and Chemistry

    2007-05-15

    The influence of growth medium on cometabolic degradation of polycyclic aromatic hydrocarbons (PAHs) was investigated when Sphingomonas sp. strain PheB4 isolated from surface mangrove sediments was grown in either phenanthrene-containing mineral salts medium (PMSM) or nutrient broth (NB). The NB-grown culture exhibited a more rapid cometabolic degradation of single and mixed non-growth substrate PAHs compared to the PMSM-grown culture. The concentrations of PAH metabolites were also lower in NB-grown culture than in PMSM-grown culture, suggesting that NB-grown culture removed metabolites at a faster rate, particularly, for metabolites produced from cometabolic degradation of a binary mixture of PAHs. Cometabolic pathways of single PAH (anthracene, fluorene, or fluoranthene) in NB-grown culture showed similarity to that in PMSM-grown culture. However, cometabolic pathways of mixed PAHs were more diverse in NB-grown culture than that in PMSM-grown culture. These results indicated that nutrient rich medium was effective in enhancing cometabolic degradation of mixed PAHs concomitant with a rapid removal of metabolites, which could be useful for the bioremediation of mixed PAHs contaminated sites using Sphingomonas sp. strain PheB4. (orig.)

  16. Stability and normal incidence reflectivity of W/B4C multilayer mirror near the boron K absorption edge.

    Science.gov (United States)

    Rao, P N; Rai, S K; Nayak, M; Lodha, G S

    2013-09-01

    A multilayer structure consisting of alternate layers of W and B4C has been deposited using a magnetron sputtering system. The structure of the as-deposited and vacuum-annealed W/B4C multilayer sample has been characterized using grazing incidence x-ray reflectivity, grazing incidence diffraction, and the normal incidence reflectivity has been measured using synchrotron radiation. A two-layer model consisting of tungsten and boron carbide is presented. The multilayer structure was found to be stable after 800°C annealing. Grazing incidence x-ray diffraction measurements suggested that W is polycrystalline with small grain size. No signature of tungsten carbide or tungsten boride formation could be observed during the annealing treatments. A near normal incidence soft x-ray reflectivity (SXRR) of ~8.3% was obtained at 6.8 nm wavelength. A little drop (~1%) in SXRR after 800°C annealing suggested that there were no compositional changes within the layers during the annealing treatments.

  17. Cloning, Sequencing, and Expression in Escherichia coli of lcnB, a Third Bacteriocin Determinant from the Lactococcal Bacteriocin Plasmid p9B4-6

    NARCIS (Netherlands)

    Belkum, Marco J. van; Kok, Jan; Venema, Gerhardus

    On the bacteriocin plasmid p9B4-6 of Lactococcus lactis subsp. cremoris 9B4, a third bacteriocin determinant was identified. The genes encoding bacteriocin production and immunity resided on a 1.2-kb CelII-ScaI fragment and were located adjacent to one of two previously identified bacteriocin

  18. Small tyrosine kinase inhibitors interrupt EGFR signaling by interacting with erbB3 and erbB4 in glioblastoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Carrasco-Garcia, Estefania; Saceda, Miguel [Instituto de Biologia Molecular y Celular, Universidad Miguel Hernandez, 03202 Elche (Alicante) (Spain); Unidad de Investigacion, Hospital General Universitario de Elche, 03203 Elche (Alicante) (Spain); Grasso, Silvina; Rocamora-Reverte, Lourdes; Conde, Mariano; Gomez-Martinez, Angeles [Instituto de Biologia Molecular y Celular, Universidad Miguel Hernandez, 03202 Elche (Alicante) (Spain); Garcia-Morales, Pilar [Instituto de Biologia Molecular y Celular, Universidad Miguel Hernandez, 03202 Elche (Alicante) (Spain); Unidad de Investigacion, Hospital General Universitario de Elche, 03203 Elche (Alicante) (Spain); Ferragut, Jose A. [Instituto de Biologia Molecular y Celular, Universidad Miguel Hernandez, 03202 Elche (Alicante) (Spain); Martinez-Lacaci, Isabel, E-mail: imlacaci@umh.es [Instituto de Biologia Molecular y Celular, Universidad Miguel Hernandez, 03202 Elche (Alicante) (Spain); Unidad AECC de Investigacion Traslacional en Cancer, Hospital Universitario Virgen de la Arrixaca, 30120 Murcia (Spain)

    2011-06-10

    Signaling through the epidermal growth factor receptor (EGFR) is relevant in glioblastoma. We have determined the effects of the EGFR inhibitor AG1478 in glioblastoma cell lines and found that U87 and LN-229 cells were very sensitive to this drug, since their proliferation diminished and underwent a marked G{sub 1} arrest. T98 cells were a little more refractory to growth inhibition and A172 cells did not undergo a G{sub 1} arrest. This G{sub 1} arrest was associated with up-regulation of p27{sup kip1}, whose protein turnover was stabilized. EGFR autophosphorylation was blocked with AG1478 to the same extent in all the cell lines. Other small-molecule EGFR tyrosine kinase inhibitors employed in the clinic, such as gefitinib, erlotinib and lapatinib, were able to abrogate proliferation of glioblastoma cell lines, which underwent a G{sub 1} arrest. However, the EGFR monoclonal antibody, cetuximab had no effect on cell proliferation and consistently, had no effect on cell cycle either. Similarly, cetuximab did not inhibit proliferation of U87 {Delta}EGFR cells or primary glioblastoma cell cultures, whereas small-molecule EGFR inhibitors did. Activity of downstream signaling molecules of EGFR such as Akt and especially ERK1/2 was interrupted with EGFR tyrosine kinase inhibitors, whereas cetuximab treatment could not sustain this blockade over time. Small-molecule EGFR inhibitors were able to prevent phosphorylation of erbB3 and erbB4, whereas cetuximab only hindered EGFR phosphorylation, suggesting that EGFR tyrosine kinase inhibitors may mediate their anti-proliferative effects through other erbB family members. We can conclude that small-molecule EGFR inhibitors may be a therapeutic approach for the treatment of glioblastoma patients.

  19. A comparison study on the densification behavior and mechanical properties of gelcast vs conventionally formed B4C sintered conventionally and by microwaves

    International Nuclear Information System (INIS)

    Menchhofer, P.A.; Kiggans, J.O.; Morrow, M.S.; Schechter, D.E.

    1996-01-01

    The utilization of microwave energy for reaching high temperatures necessary to densify B 4 C powder is compared with conventional means of sintering by evaluating the mechanical properties after densification. Microwave energy has been shown to be an effective means for achieving high sintered densities, even though temperatures of ∼ 2,250 C are required. In this study, green preforms of B 4 C specimens were sintered by both conventional and microwave heating. This study also utilized an advanced forming method called ''Gelcasting'' developed at ORNL. Gelcasting is a fluid forming process whereby high solids suspensions of powders containing dissolved monomers are cast into a mold, then polymerized or ''gelled'' in situ. This investigation compares microstructures and mechanical properties of both Gelcast B 4 C and ''conventionally'' die-pressed B 4 C. The microstructures and final mechanical properties of B 4 C specimens are discussed

  20. Human UDP-Glucuronosyltransferase 2B4 and 2B7 Are Responsible for Naftopidil Glucuronidation in Vitro

    Directory of Open Access Journals (Sweden)

    Xia-Wen Liu

    2018-01-01

    Full Text Available Naftopidil (NAF is widely used for the treatment of benign prostatic hyperplasia and prevention of prostate cancer in elderly men. These patients receive a combination of drugs, which involves high risk for drug–drug interaction. NAF exhibits superior efficacy but must be administered at a much higher dosage than other therapeutic drugs. We previously showed that extensive glucuronidation of NAF enantiomers caused poor bioavailability. However, the metabolic pathway and mechanism of action of NAF enantiomer remain to be elucidated. The present study was performed to identify the human UDP-glucuronosyltransferases (UGTs responsible for the glucuronidation of NAF enantiomers and to investigate the potential inhibition of UGT activity by NAF. The major metabolic sites examined were liver and kidney, which were compared with intestine. Screening of 12 recombinant UGTs showed that UGT2B7 primarily contributed to the metabolism of both enantiomers. Moreover, enzyme kinetics for R(+-NAF, UGT2B7 (mean Km, 21 μM; mean Vmax, 1043 pmol/min/mg showed significantly higher activity than observed for UGT2B4 and UGT1A9. UGT2B4 (mean Km, 55 μM; mean Vmax, 1976 pmol/min/mg and UGT2B7 (mean Km, 38 μM; mean Vmax, 1331 pmol/min/mg showed significantly higher catalysis of glucuronidation of S(--NAF than UGT1A9. In human liver microsomes, R(+-NAF and S(--NAF also inhibited UGT1A9: mean Ki values for R(+-NAF and S(--NAF were 10.0 μM and 11.5 μM, respectively. These data indicate that UGT2B7 was the principal enzyme mediating glucuronidation of R(+-NAF and S(--NAF. UGT2B4 plays the key role in the stereoselective metabolism of NAF enantiomers. R(+-NAF and S(--NAF may inhibit UGT1A9. Understanding the metabolism of NAF enantiomers, especially their interactions with metabolic enzymes, will help to elucidate potential drug–drug interactions and to optimize the administration of this medicine.

  1. TL response of MgB4O7: Dy, Na in function of the gamma radiation dose

    International Nuclear Information System (INIS)

    Cano, A.; Gonzalez, P.R.; Furetta, C.

    2007-01-01

    Full text: In this work the obtained results of the irradiation of thermoluminescent dosemeters of MgB 4 O 7 ;Dy,Na, with gamma radiation of 137 Cs and 60 Co, in a dose interval between 0.2 mGy and 1000 Gy are presented. The regions of linearity, supralineality and of saturation of their TL response are shown. Its also show the results of the tests of sensitivity of these new dosemeters, its detection threshold, the reproducibility in its TL response to the radiation, as well as the stability of the information. It also determines their effective atomic number (Z eff ). The results show that these dosemeters are promissory to use them in the different medical applications of the radiation. (Author)

  2. Study of coexistence of ferromagnetism and superconductivity in single-crystal ErRh4B4

    International Nuclear Information System (INIS)

    Sinha, S.K.; Crabtree, G.W.; Hinks, D.G.; Mook, H.

    1981-01-01

    Neutron diffraction and resistivity measurements on single crystals of ErRh 4 B 4 have revealed that both superconductivity and ferromagnetic order coexist in this material between 0.71 and 1.2 0 K. In this intermediate phase, a linear polarized modulated structure with a wavelength of approximately 100 A is observed. The modulated moment increases faster than the ferromagnetic moment down to 0.71 K and then disappears suddenly, with loss of superconductivity and a transition to a normal ferromagnetic state. This transition is accompanied by temperature hysteresis of about 60 mK. The same hysteresis, in the inverse sense, is exhibited by the ferromagnetic component. We interpret the intermediate phase as being one of coexisting normal ferromagnetic domains and superconducting sinusoidally ordered domains. Evidence of a small percentage of small ferromagnetic regions of size approx. 100 A is also seen in both the intermediate and ferromagnetic phases. 3 figures

  3. Reactivity and neutron flux measurements in IPEN/MB-01 reactor with B4C burnable poison

    International Nuclear Information System (INIS)

    Fer, Nelson Custodio; Moreira, Joao Manoel Losada

    2000-01-01

    Burnable poison rods, made of B 4 C- Al 2 O 3 pellets with 5.01 mg/cm 3 10 B concentration, have been manufactured for a set of experiments in the IPEN/MB-01 zero-power reactor. Several core parameters which are affected by the burnable poisons rods have been measured. The principal results, for the situation in which the burnable poison rods are located near the absorber rods of a control rod, are they cause a 29% rod worth shadowing, a reduction of 39% in the local void coefficient of reactivity, a reduction of 4.8% in the isothermal temperature coefficient of reactivity, and a reduction of 9% in the thermal neutron flux in the region where the burnable poison rods are located. These experimental results will be used for the validation of burnable poison calculation methods in the CTMSP. (author)

  4. Interleukin-8 and leukotriene B4 in bronchoalveolar lavage fluid from HIV-infected patients with bacterial pneumonia

    DEFF Research Database (Denmark)

    Krarup, E; Vestbo, Jørgen; Benfield, T L

    1997-01-01

    Human immunodeficiency virus (HIV)-infected patients are at increased risk of contracting bacterial infections, mainly pneumonia. Despite this, little is known about immunopathogenic mechanisms in HIV-related bacterial pneumonia. This paper investigates the presence of the neutrophil chemotactic...... mediators, interleukin-8 (IL_8) and leukotriene B4 (LTB4), in bronchoalveolar lavage (BAL) fluid from 27 HIV-infected patients with bacterial pneumonia. Significantly elevated levels of IL-8 were found in BAL fluid of patients with bacterial pneumonia [529 pg ml-1 (296-1161 pg ml-1)] compared to matched...... patients with Pneumocystis carinii pneumonia (PCP) [59 pg ml-1 (42-254 pg ml-1)] and healthy controls [58 pg ml-1 (37-82 pg ml-1)]. Levels of LTB4 were not elevated during bacterial pneumonia when compared to PCP patients and healthy controls. Furthermore, a positive correlation was found between IL-8...

  5. Non-contact XUV metrology of Ru/B4C multilayer optics by means of Hartmann wavefront analysis.

    Science.gov (United States)

    Ruiz-Lopez, Mabel; Dacasa, Hugo; Mahieu, Benoit; Lozano, Magali; Li, Lu; Zeitoun, Philippe; Bleiner, Davide

    2018-02-20

    Short-wavelength imaging, spectroscopy, and lithography scale down the characteristic length-scale to nanometers. This poses tight constraints on the optics finishing tolerances, which is often difficult to characterize. Indeed, even a tiny surface defect degrades the reflectivity and spatial projection of such optics. In this study, we demonstrate experimentally that a Hartmann wavefront sensor for extreme ultraviolet (XUV) wavelengths is an effective non-contact analytical method for inspecting the surface of multilayer optics. The experiment was carried out in a tabletop laboratory using a high-order harmonic generation as an XUV source. The wavefront sensor was used to measure the wavefront errors after the reflection of the XUV beam on a spherical Ru/B 4 C multilayer mirror, scanning a large surface of approximately 40 mm in diameter. The results showed that the technique detects the aberrations in the nanometer range.

  6. Effect of sintering temperature on microstructure and compressive strength of B4C-AlSi eutectic alloy

    International Nuclear Information System (INIS)

    Liu Jinyun; Zha Wusheng; Liu Gaihua; Lan Jun; Feng Quanhe; Zou Congpei

    2008-01-01

    The block neutron absorber of B 4 C based on Al-Si eutectic alloy has been prepared by powder-metallurgy method. The effects of sinter temperature on microstructure, compressive strength, and ductility of sintered billets have been investigated. It has been shown that the sintering temperature decides sensitively the compressive strength and ductility of sintered billets. Sintered under 550, 555, 560, and 565 degree C, the billet shows different states, such as sub-sintered, best-sintered, over-sintered, and molten. Sintered under 550 degree C, the powder have not been metallurgically combined with each other. Beyond 560 degree C, the billets are molten. The 555 degree C is the best sintering temperature, under which the powder have been partly melted and the metallurgical combination has been occurred, then the billets have a better ductility. (authors)

  7. Specially designed B4C/SnO2 nanocomposite for photocatalysis: traditional ceramic with unique properties

    Science.gov (United States)

    Singh, Paviter; Kaur, Gurpreet; Singh, Kulwinder; Singh, Bikramjeet; Kaur, Manpreet; Kaur, Manjot; Krishnan, Unni; Kumar, Manjeet; Bala, Rajni; Kumar, Akshay

    2018-02-01

    Boron carbide: A traditional ceramic material shows unique properties when explored in nano-range. Specially designed boron-based nanocomposite has been synthesized by reflux method. The addition of SnO2 in base matrix increases the defect states in boron carbide and shows unique catalytic properties. The calculated texture coefficient and Nelson-Riley factor show that the synthesized nanocomposite has large number of defect states. Also this composite is explored for the first time for catalysis degradation of industrial used dyes. The degradation analysis of industrial pollutants such as Novacron red Huntsman (NRH) and methylene blue (MB) dye reveals that the composite is an efficient catalyst. Degradation study shows that 1 g/L catalyst concentration of B4C/SnO2 degrades NRH and MB dye up to approximately 97.38 and 79.41%, respectively, in 20 min under sunlight irradiation. This water-insoluble catalyst can be recovered and reused.

  8. Biochemical Analysis of CagE: A VirB4 Homologue of Helicobacter pylori Cag-T4SS.

    Directory of Open Access Journals (Sweden)

    Mohd Shariq

    Full Text Available Helicobacter pylori are among the most successful human pathogens that harbour a distinct genomic segment called cag Pathogenicity Island (cag-PAI. This genomic segment codes for a type IV secretion system (Cag-T4SS related to the prototypical VirB/D4 system of Agrobacterium tumefaciens (Ag, a plant pathogen. Some of the components of Cag-T4SS share homology to that of VirB proteins including putative energy providing CagE (HP0544, the largest VirB4 homologue. In Ag, VirB4 is required for the assembly of the system, substrate translocation and pilus formation, however, very little is known about CagE. Here we have characterised the protein biochemically, genetically, and microscopically and report that CagE is an inner membrane associated active NTPase and has multiple interacting partners including the inner membrane proteins CagV and Cagβ. Through CagV it is connected to the outer membrane sub-complex proteins. Stability of CagE is not dependent on several of the cag-PAI proteins tested. However, localisation and stability of the pilus associated CagI, CagL and surface associated CagH are affected in its absence. Stability of the inner membrane associated energetic component Cagβ, a VirD4 homologue seems to be partially affected in its absence. Additionally, CagA failed to cross the membrane barriers in its absence and no IL-8 induction is observed under infection condition. These results thus suggest the importance of CagE in Cag-T4SS functions. In future it may help in deciphering the mechanism of substrate translocation by the system.

  9. Pso p27, a SERPINB3/B4-derived protein, is most likely a common autoantigen in chronic inflammatory diseases.

    Science.gov (United States)

    Iversen, Ole-Jan; Lysvand, Hilde; Slupphaug, Geir

    2017-01-01

    Autoimmune diseases are characterized by chronic inflammatory reactions localized to an organ or organ-system. They are caused by loss of immunologic tolerance toward self-antigens, causing formation of autoantibodies that mistakenly attack their own body. Psoriasis is a chronic inflammatory autoimmune skin disease in which the underlying molecular mechanisms remain elusive. In this review, we present evidence accumulated through more than three decades that the serpin-derived protein Pso p27 is an autoantigen in psoriasis and probably also in other chronic inflammatory diseases. Pso p27 is derived from the serpin molecules SERPINB3 and SERPINB4 through non-canonical cleavage by mast cell chymase. In psoriasis, it is exclusively found in skin lesions and not in uninvolved skin. The serpins are cleaved into three fragments that remain associated as a Pso p27 complex with novel immunogenic properties and increased tendency to form large aggregates compared to native SERPINB3/B4. The amount of Pso p27 is directly correlated to disease activity, and through formation of complement activating immune-complexes, Pso p27 contribute to the inflammation in the skin lesions. SERPINB3/B4 are expressed in skin fibroblasts and keratinocytes, but normally absent in mast cells. Overexpression of the serpins may be induced by inflammation and hypoxia, resulting in mast cell uptake via yet unknown mechanisms. Here the generation and subsequent release of Pso p27 aggregates may promote an inflammatory loop that contributes to the chronicity of psoriasis and other autoimmune diseases. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Optical performance of W/B4C multilayer mirror in the soft x-ray region

    Science.gov (United States)

    Pradhan, P. C.; Majhi, A.; Nayak, M.

    2018-03-01

    W/B4C x-ray multilayers (MLs) with 300 layer pairs and a period in the range of d = 2-1.6 nm are fabricated and investigated for the x-ray optical element in the soft x-ray regime. The structural analyses of the MLs are carried out by using hard x-ray reflectivity (HXR) measurements at 8.047 keV. Well-defined successive higher order Bragg peaks (up to 3rd order) in HXR data collected up to glancing incidence angles of ˜9° reveal a good quality of the periodic structure. The ML mirrors have an average interface width of ˜0.35 nm and have a compressive residual stress of ˜0.183 GPa and 0. 827 GPa for d = 1.62 nm and d = 1.98 nm, respectively. MLs maintain structural stability over a long time, with a slight increase in interface widths of the W layers by 0.1 nm due to self-diffusion. Soft x-ray reflectivity (SXR) performances are evaluated in the energy range of 650 to 1500 eV. At energy ˜ 1489 eV, measured reflectivities (energy resolution, ΔE) are ˜ 10% (19 eV) and 4.5% (13 eV) at glancing incident angles of 12.07° and 15° for MLs having periods of 1.98 nm and 1.62 nm, respectively. The optical performance from 1600 eV to 4500 eV is theoretically analysed by considering the measured structural parameters. The structure-stress-optical performance is correlated on the basis of the mechanism of film growth. The implications of W/B4C MLs are discussed, particularly with respect to the development of ML optics with high spectral selectivity and reflectance for soft x-ray instruments.

  11. Ballistic Impact Behavior of Nacre-Like Laminated Composites Consisting of B4C Tablets and Polyurea Matrix

    Science.gov (United States)

    Grujicic, M.; Snipes, J. S.; Ramaswami, S.

    2016-03-01

    A nacre-like composite armor consisting of B4C tablets and polyurea matrix is modeled, and its ballistic impact behavior and penetration resistance (under a normal and a 15°-oblique impact by a solid right circular cylindrical projectile) were analyzed using a series of transient, nonlinear dynamic, finite-element analyses. Nacre is a biological material constituting the innermost layer of the shells of gastropods and bivalves. It consists of polygonal tablets of aragonite, tessellated to form individual layers and having the adjacent layers as well as the tablets within a layer bonded by a biopolymer. Due to its highly complex hierarchical microstructure, nacre possesses an outstanding combination of mechanical properties, the properties which are far superior to the ones that are predicted using the homogenization techniques such as the rule of mixtures. The results of the transient nonlinear dynamic analysis pertaining to the ballistic impact response and the penetration resistance of the modeled nacre-like armor are compared with their counterparts for the B4C single-block armor having an identical areal density. Furthermore, the effect of various nacre microstructural features (e.g., surface profiling, micron-scale asperities, mineral bridges between the overlapping tablets lying in adjacent layers) on the ballistic penetration resistance of the nacre-like composite armor is investigated in order to identify an optimal nacre-like composite-armor architecture having the largest penetration resistance. The results obtained clearly show that a nacre-like armor possesses a superior penetration resistance relative to its monolithic counterpart, and that the nacre microstructural features considered play a critical role in the armor penetration resistance.

  12. FXR induces the UGT2B4 enzyme in hepatocytes : A potential mechanism of negative feedback control of FXR activity

    NARCIS (Netherlands)

    Barbier, O; Pineda Torra, I.; Sirvent, A; Claudel, T; Blanquart, C; Duran-Sandoval, D; Kuipers, F; Kosykh, V.; Fruchart, JC; Staels, B

    Background & Aims: Bile acids are essential for bile formation and Intestinal absorption of lipids and fat-soluble vitamins. However, the intrinsic toxicity of hydrophobic bile acids demands a tight control of their intracellular concentrations. Bile acids are ligands for the farnesoid X receptor

  13. Somatostatin receptors

    DEFF Research Database (Denmark)

    Møller, Lars Neisig; Stidsen, Carsten Enggaard; Hartmann, Bolette

    2003-01-01

    therefore been acknowledged to be a third endogenous ligand at SRIF receptors. This review goes through mechanisms of signal transduction, pharmacology, and anatomical distribution of SRIF receptors. Structurally, SRIF receptors belong to the superfamily of G protein-coupled (GPC) receptors, sharing....... The generation of knock-out (KO) mice, intended as a means to define the contributions made by individual receptor subtypes, necessarily marks but an approximation. Furthermore, we must now take into account the stunning complexity of receptor co-operation indicated by the observation of receptor homo......-peptides, receptor agonists and antagonists. Relatively long half lives, as compared to those of the endogenous ligands, have been paramount from the outset. Motivated by theoretical puzzles or the shortcomings of present-day diagnostics and therapy, investigators have also aimed to produce subtype...

  14. Rapid Biosynthesis of Silver Nanoparticles Based on Flocculation and Reduction of an Exopolysaccharide from Arthrobacter sp. B4: Its Antimicrobial Activity and Phytotoxicity

    Directory of Open Access Journals (Sweden)

    Li Yumei

    2017-01-01

    Full Text Available Silver nanoparticles (AgNPs were rapidly synthesized using an exopolysaccharide from Arthrobacter sp. B4 (B4-EPS. The optimum condition for AgNPs synthesis was under the concentration of 5 g/L B4-EPS and 1 mM AgNO3 at 80°C between pH 7.0 and 8.0. The resulting AgNPs displayed a face-centred-cubic structure with the size range from 9 nm to 72 nm. Further analysis showed that flocculation and reduction of B4-EPS played a pivotal role in the formation of AgNPs. Furthermore, these nanoparticles exhibited great stability, excellent antimicrobial activity, and low phytotoxicity. The aforementioned data provide a feasible and efficient approach for green synthesis of AgNPs using microbial polysaccharides with flocculation and reduction activity, which will be promising in medical filed.

  15. 17 CFR 240.3b-4 - Definition of “foreign government,” “foreign issuer” and “foreign private issuer”.

    Science.gov (United States)

    2010-04-01

    ... government,â âforeign issuerâ and âforeign private issuerâ. 240.3b-4 Section 240.3b-4 Commodity and... Definition of “foreign government,” “foreign issuer” and “foreign private issuer”. (a) The term foreign... country. (c) The term foreign private issuer means any foreign issuer other than a foreign government...

  16. Protection against type 1 diabetes upon Coxsackievirus B4 infection and iNKT-cell stimulation: role of suppressive macrophages.

    Science.gov (United States)

    Ghazarian, Liana; Diana, Julien; Beaudoin, Lucie; Larsson, Pär G; Puri, Raj K; van Rooijen, Nico; Flodström-Tullberg, Malin; Lehuen, Agnès

    2013-11-01

    Invariant natural killer T (iNKT) cells belong to the innate immune system and exercise a dual role as potent regulators of autoimmunity and participate in responses against different pathogens. They have been shown to prevent type 1 diabetes development and to promote antiviral responses. Many studies in the implication of environmental factors on the etiology of type 1 diabetes have suggested a link between enteroviral infections and the development of this disease. This study of the pancreatropic enterovirus Coxsackievirus B4 (CVB4) shows that although infection accelerated type 1 diabetes development in a subset of proinsulin 2-deficient NOD mice, the activation of iNKT cells by a specific agonist, α-galactosylceramide, at the time of infection inhibited the disease. Diabetes development was associated with the infiltration of pancreatic islets by inflammatory macrophages, producing high levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α and activation of anti-islet T cells. On the contrary, macrophages infiltrating the islets after CVB4 infection and iNKT-cell stimulation expressed a number of suppressive enzymes, among which indoleamine 2,3-dioxygenase was sufficient to inhibit anti-islet T-cell response and to prevent diabetes. This study highlights the critical interaction between virus and the immune system in the acceleration or prevention of type 1 diabetes.

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

    Directory of Open Access Journals (Sweden)

    Xiao-Feng Lai

    2014-11-01

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

  18. Laser induced fluorescence of TiD: analysis of the B4Γ-X4Φ transition

    International Nuclear Information System (INIS)

    Danielsson, M

    2007-01-01

    A titanium hollow cathode lamp in combination with a dye laser and a monochromator has been used to resolve the laser-induced fluorescence of the TiD molecule. This has enabled the extension of the earlier rotational analysis of the (0,0) band of the B 4 Γ-X 4 Φ transition. In addition, the (1,1) band and part of the (2,2) band have been observed and analyzed. All earlier works on the TiD and TiH molecules concern the (0,0) band. The present work is the first to report experimentally determined equilibrium constants for TiD. For the ground state X 4 Φ the principal parameters are (in cm -1 ) A e =33.075, B e =2.7804, D e =6.819x10 -5 and α e =0.0466. By using the isotope relationships the corresponding equilibrium parameters for the TiH molecule are given

  19. Effects of academic exam stress on nasal leukotriene B4 and vascular endothelial growth factor in asthma and health.

    Science.gov (United States)

    Trueba, Ana; Ryan, Matthew W; Vogel, Pia D; Ritz, Thomas

    2016-07-01

    To examine the effect of final exam stress on the concentrations of leukotriene B4 (LTB4) and vascular endothelial growth factor (VEGF) in the upper airways among healthy and asthmatic individuals. Nasal samples were collected from 12 individuals with asthma and 23 healthy controls early and late in a final exam period, and during a low-stress period in the semester. We determined LTB4 and VEGF concentrations using Enzyme-Linked Immunoassays. Mixed effects analysis of variance models showed that asthmatic participants with allergies in contrast to healthy individuals experienced a decrease in nasal LTB4 during the final exam period as compared to mid-semester (low stress period). There were no significant changes in nasal VEGF across the observation period. Changes in nasal LTB4 and VEGF were not associated with salivary cortisol, exhaled nitric oxide, or spirometric lung function. Our results suggest that nasal LTB4 concentrations change in periods of psychological stress for asthmatic individuals with allergies. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    D. Carlos

    2011-04-01

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

  1. Properties of B4C in the shocked state for pressures up to 1.5 TPa

    Science.gov (United States)

    Shamp, Andrew; Zurek, Eva; Ogitsu, Tadashi; Fratanduono, Dayne E.; Hamel, Sebastien

    2017-05-01

    Density functional theory calculations using the quasiharmonic approximation have been used to calculate the solid Hugoniot of two polytypes of boron carbide up to 100 GPa. Under the assumption that segregation into the elemental phases occurs around the pressure that the B11Cp (CBC) polytype becomes thermodynamically unstable with respect to boron and carbon, two discontinuities in the Hugoniot, one at 50 GPa and one at 90-100 GPa, are predicted. The former is a result of phase segregation, and the latter a phase transition within boron. First-principles molecular dynamics (FPMD) simulations were employed to calculate the liquid Hugoniot of B4C up to 1.5 TPa, and the results are compared to recent experiments carried out at the Omega Laser Facility up to 700 GPa [D. E. Fratanduono, Phys. Rev. B 94, 184107 (2016), 10.1103/PhysRevB.94.184107]. A generally good agreement between theory and experiment was observed. Analysis of the FPMD simulations provides evidence for an amorphous, but covalently bound, fluid below 438 GPa, and an atomistic fluid at higher pressures and temperatures.

  2. Characterization of Carbon-Contaminated B4C-Coated Optics after Chemically Selective Cleaning with Low-Pressure RF Plasma.

    Science.gov (United States)

    Moreno Fernández, H; Rogler, D; Sauthier, G; Thomasset, M; Dietsch, R; Carlino, V; Pellegrin, E

    2018-01-22

    Boron carbide (B 4 C) is one of the few materials that is expected to be most resilient with respect to the extremely high brilliance of the photon beam generated by free electron lasers (FELs) and is thus of considerable interest for optical applications in this field. However, as in the case of many other optics operated at light source facilities, B 4 C-coated optics are subject to ubiquitous carbon contaminations. Carbon contaminations represent a serious issue for the operation of FEL beamlines due to severe reduction of photon flux, beam coherence, creation of destructive interference, and scattering losses. A variety of B 4 C cleaning technologies were developed at different laboratories with varying success. We present a study regarding the low-pressure RF plasma cleaning of carbon contaminated B 4 C test samples via inductively coupled O 2 /Ar, H 2 /Ar, and pure O 2 RF plasma produced following previous studies using the same ibss GV10x downstream plasma source. Results regarding the chemistry, morphology as well as other aspects of the B 4 C optical coating before and after the plasma cleaning are reported. We conclude that among the above plasma processes only plasma based on pure O 2 feedstock gas exhibits the required chemical selectivity for maintaining the integrity of the B 4 C optical coatings.

  3. First-principles investigation of neutron-irradiation-induced point defects in B4C, a neutron absorber for sodium-cooled fast nuclear reactors

    Science.gov (United States)

    You, Yan; Yoshida, Katsumi; Yano, Toyohiko

    2018-05-01

    Boron carbide (B4C) is a leading candidate neutron absorber material for sodium-cooled fast nuclear reactors owing to its excellent neutron-capture capability. The formation and migration energies of the neutron-irradiation-induced defects, including vacancies, neutron-capture reaction products, and knocked-out atoms were studied by density functional theory calculations. The vacancy-type defects tend to migrate to the C–B–C chains of B4C, which indicates that the icosahedral cage structures of B4C have strong resistance to neutron irradiation. We found that lithium and helium atoms had significantly lower migration barriers along the rhombohedral (111) plane of B4C than perpendicular to this plane. This implies that the helium and lithium interstitials tended to follow a two-dimensional diffusion regime in B4C at low temperatures which explains the formation of flat disk like helium bubbles experimentally observed in B4C pellets after neutron irradiation. The knocked-out atoms are considered to be annihilated by the recombination of the close pairs of self-interstitials and vacancies.

  4. Photocatalytic CO2 reduction over B4C/C3N4 with internal electric field under visible light irradiation.

    Science.gov (United States)

    Zhang, Xiaojie; Wang, Lei; Du, Quanchao; Wang, Zhiyong; Ma, Shuguo; Yu, Miao

    2016-02-15

    Boron carbide/graphitic carbon nitride (B4C/g-C3N4) p-n hetero-junction photocatalyst with an internal electric field was synthesized by a facile solvent evaporation method and characterized by field emission scanning electron microscope (FESEM), UV-Vis diffuse reflectance spectra (UV-Vis DRS), photoluminescence spectra (PL), etc. Photocatalytic activity of the composite B4C/g-C3N4 loaded with Pt co-catalyst was evaluated using CO2 conversion to CH4 with H2 as the hydrogen source and reductant under visible light irradiation. The coupling of p-type B4C with n-type g-C3N4 significantly improved the performance of photocatalytic CO2 reduction; with the optimum B4C mass fraction of 1/6, the composite photocatalyst showed approximately 6 and 8 times higher CH4 generation rate than g-C3N4 and B4C, respectively. The enhancement was attributed to efficient photo-excited electron/hole separation due to the formation of internal electric field at the p-B4C/n-C3N4 interface. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Somatostatin receptors

    DEFF Research Database (Denmark)

    Møller, Lars Neisig; Stidsen, Carsten Enggaard; Hartmann, Bolette

    2003-01-01

    therefore been acknowledged to be a third endogenous ligand at SRIF receptors. This review goes through mechanisms of signal transduction, pharmacology, and anatomical distribution of SRIF receptors. Structurally, SRIF receptors belong to the superfamily of G protein-coupled (GPC) receptors, sharing......- and heterodimerisation, let alone oligomerisation. Theoretically, this phenomenon adds a novel series of functional megareceptors/super-receptors, with varied pharmacological profiles, to the catalogue of monomeric receptor subtypes isolated and cloned in the past. SRIF analogues include both peptides and non......-peptides, receptor agonists and antagonists. Relatively long half lives, as compared to those of the endogenous ligands, have been paramount from the outset. Motivated by theoretical puzzles or the shortcomings of present-day diagnostics and therapy, investigators have also aimed to produce subtype...

  6. Distinct EphB4-mediated mechanisms of apoptotic and resistance to dasatinib in human chronic myeloid leukemia and K562 cell lines.

    Science.gov (United States)

    Zhao, Wei-Hong; Huang, Bin-Tao; Zhang, Jian-Yu; Zeng, Qing-Chun

    2017-12-01

    To determine the role and mechanism of EphB4 in dasatinib (DAS) resistance in advanced chronic myeloid leukemia (CML), we explored the EphB4-mediated apoptotic and matrix microenvironment pathway in human CML and K562 cell lines. Heparinized bone marrow samples were obtained from enrolled five patients (identified as A to E and visits identified by number) at initial diagnosis (A1-E1) and in the DAS-resistance advanced phase (A2-E2). Meanwhile, highly DAS-resistant cells, named K562-R cells, were obtained from K562-W cells with increasing concentrations of DAS. Stable under-expressing EphB4 cells (K562-R-EphB4-sh) were obtained from K562-R cells by RNA interference. K562-W, K562-R and K562-R-EphB4-sh cells (10 8 ) were respectively injected subcutaneously on the dorsal surface of BALB/C female nude mice to establish the xenografts models. The mRNA/protein of EphB4 was overexpressed in the DAS-resistant A2-E2 in comparison with the A1-E1 human cell lines. Further, compared with K562-R cells, the expressions of EphB4 and p-Rac1/Cdc42 protein/mRNA were significantly downregulated in K562-R-EphB4-sh cells (P<0.01). K562-R cells showed the highest DAS resistance (IC50 10.54±0.67μg/ml), but K562-R-EphB4-sh cells became sensitive to DAS (IC50 1.02±0.1μg/ml, P<0.01). The expression of EphB4/p-RhoA/MCL-1 protein was gradually increased in the stimulating of EphrinB2-Fc, which partly made K562-R-EphB4-sh cells restore sensitivity to DAS (4.18±0.30μg/ml). Meanwhile, the K562-R-EphB4-sh xenografts group had relatively good efficacy compared to K562-R xenografts nude mice receiving the same dose of DAS. The analysis of xenografts tissue also suggested parallel results with the overexpression of EphB4/RhoA/ROCK1/PTEN/MCL-1 in K562-R xenografts, which decreased in the A2-R-EphB4-sh xenografts (P<0.01). The present study found that a new DAS resistance pathway of EphB4 overexpression was triggered by EphrinB2-Fc, which induced the resistance to DAS by activating RhoA/ROCK1

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

    International Nuclear Information System (INIS)

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

    1986-01-01

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

  8. Hybridizing micro-Ti with nano-B4C particulates to improve the microstructural and mechanical characteristics of Mg–Ti composite

    Directory of Open Access Journals (Sweden)

    S. Sankaranarayanan

    2014-03-01

    Full Text Available In this study, the effects of hybridizing micron-sized titanium particles with nano-sized boron carbide particles on the microstructural and mechanical properties of Mg–Ti composite were investigated. Microstructural characterization revealed grain refinement attributed to the presence of uniformly distributed micro-Ti particles embedded with nano-B4C particulates. Electron back scattered diffraction (EBSD analyses of the Mg–(Ti + B4CBM hybrid composite showed relatively more localized recrystallized grains and lesser tensile twin fraction, when compared to Mg–Ti. The evaluation of mechanical properties indicated that the best combination of strength and ductility was observed in the Mg–(Ti + B4CBM hybrid composite. The superior properties of the Mg–(Ti + B4CBM hybrid composite when compared to Mg–Ti can be attributed to the presence of nano-reinforcement, the uniform distribution of the hybridized particles and the better interfacial bonding between the matrix and the reinforcement particles achieved by nano-B4C addition.

  9. A phase III study of anti-B4-blocked ricin as adjuvant therapy post-autologous bone marrow transplant: CALGB 9254

    Science.gov (United States)

    Furman, Richard R.; Grossbard, Michael L.; Johnson, Jeffrey L.; Pecora, Andrew L.; Cassileth, Peter A.; Jung, Sin-Ho; Peterson, Bruce A.; Nadler, Lee M.; Freedman, Arnold; Bayer, Ruthee-Lu; Bartlett, Nancy L.; Hurd, David D.; Cheson, Bruce D.

    2013-01-01

    Anti-B4-blocked ricin (anti-B4-bR) is a potent immunotoxin directed against the CD 19 antigen. Previous phase I and II studies suggested a possible role for anti-B4-bR as consolidation after high-dose chemotherapy and autologous stem cell transplant. Cancer and Leukemia Group B (CALGB) 9254 is a phase III study which randomized 157 patients with B-cell lymphoma in complete remission following autologous transplant to treatment with anti-B4-bR or observation. With a median follow-up time for patients of 5.8 years, the median event-free survival for protocol treatment and observation are 2.1 and 2.9 years, respectively (p = 0.275). The median overall survival for treatment and observation are 6.1 years and not reached, respectively (p = 0.063). Therefore, no differences were found in event-free survival and overall survival between protocol treatment and observation, although there was a trend toward improved survival with observation. These data fail to support a role for anti-B4-bR as consolidative therapy after bone marrow transplant in patients with B-cell lymphoma. PMID:21275630

  10. Table-like magnetocaloric effect of Fe88−xNdxCr8B4 composite materials

    International Nuclear Information System (INIS)

    Lai, J.W.; Zheng, Z.G.; Zhong, X.C.; Franco, V.; Montemayor, R.; Liu, Z.W.; Zeng, D.C.

    2015-01-01

    The narrow working temperature range due to the sharp magnetic entropy change |ΔS M | peak and large thermal or magnetic hysteresis restricts the practical application of magnetocaloric materials. In this work, the table-like magnetocaloric effect (MCE) was obtained in the multilayer composite of Fe 88−x Nd x Cr 8 B 4 alloys with various Nd substitutions for Fe (x=5, 8, 10, 12, and 15), which were prepared by arc-melting followed by melt-spinning. The substation of Nd was found to enhance the glass-forming ability. For the alloys with Nd substitution from 5 at% to 15 at%, the Curie temperature (T C ) ranged from 322 K to 350 K and the peak value of |ΔS M | remained almost constant, 3.4–3.5 J/(kg K) under an applied field of 0–5 T. The composite with various Nd contents was prepared by stocking the ribbons layer by layer. The |ΔS M | of the composite approached a nearly constant value of ∼3.2 J/(kg K) in a field change of 0–5 T in a wide temperature span over 40 K, resulting in large refrigerant capacity value of >408 J/kg. This |ΔS M | value was much larger than the previous reported Fe-based amorphous composite Fe 78−x Ce x Si 4 Nb 5 B 12 Cu 1 . This composite can be used as the working material in the Ericsson-cycle magnetic regenerative refrigerator around room temperature. - Highlights: • The T C ranges from 322 K to 350 K when increasing Nd substitution from 5 to 15 at%. • |ΔS M | remains relatively constant, about 3.4–3.5 J/(kg K) under H=0–5 T. • RC decreases from 93 to 78 J/kg in a field change of 1.5 T when Nd increasing. • Table-like MCE ,|ΔS M | ~3.2J/kg K under 0–5 T, appeared in the composite. • A wide working temperature range (40 K) and enhanced RC (>408J/kg) were obtained in the composite

  11. Friction Stir Welding of Al-B4C Composite Fabricated by Accumulative Roll Bonding: Evaluation of Microstructure and Mechanical Behavior

    Science.gov (United States)

    Moradi Faradonbeh, Alireza; Shamanian, Morteza; Edris, Hossein; Paidar, Moslem; Bozkurt, Yahya

    2018-02-01

    In this investigation, friction stir welding (FSW) of Al-B4C composite fabricated by 10 cycles accumulative roll bonding was conducted. In order to investigate the influences of pin geometry on microstructure and mechanical properties, four different pin geometries (cylindrical, square, triangular and hexagonal) were selected. It was found that FSW parameters had a major effect on the fragmentation and distribution of reinforcement particles in stir zone. When the tool travel speed was increased, the distribution of B4C particles was become gradually uniform in the aluminum matrix. The effect of tool rotational speed on the peak temperature was determined to be greater than the tool travel speed. The attained data of tensile properties and microhardness tests showed that the tool travel speed had bilateral effect on the tensile strength. The maximum tensile joint efficiency was obtained as 238% for FSWed of Al-2%B4C composite to annealed base Al sheet.

  12. Influence of B4C-doping and high-energy ball milling on phase formation and critical current density of (Bi,Pb)-2223 HTS

    Science.gov (United States)

    Margiani, N. G.; Mumladze, G. A.; Adamia, Z. A.; Kuzanyan, A. S.; Zhghamadze, V. V.

    2018-05-01

    In this paper, the combined effects of B4C-doping and planetary ball milling on the phase evolution, microstructure and transport properties of Bi1.7Pb0.3Sr2Ca2Cu3Oy(B4C)x HTS with x = 0 ÷ 0.125 were studied through X-ray diffraction (XRD), scanning electron microscopy (SEM), resistivity and critical current density measurements. Obtained results have shown that B4C additive leads to the strong acceleration of high-Tc phase formation and substantial enhancement in Jc. High-energy ball milling seems to produce a more homogeneous distribution of refined doped particles in the (Bi,Pb)-2223 HTS which results in an improved intergranular flux pinning and better self-field Jc performance.

  13. Preparation and characteristics of epoxy/clay/B4C nanocomposite at high concentration of boron carbide for neutron shielding application

    Science.gov (United States)

    Kiani, Mohammad Amin; Ahmadi, Seyed Javad; Outokesh, Mohammad; Adeli, Ruhollah; Mohammadi, Aghil

    2017-12-01

    In this research, the characteristics of the prepared samples in epoxy matrix by means of X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDS), as well as scanning electron microscope (SEM) are evaluated. Meanwhile, the obtained mechanical properties of the specimen are investigated. Thermogravimetric analysis (TGA) is also employed to evaluate the thermal degradation of manufactured nanocomposites. The thermal neutron absorption properties of nanocomposites containing 3 wt% of montmorillonite nanoclay (closite30B) have been studied experimentally, using an Am-Be point source. Mechanical tests reveal that the higher B4C concentrations, the more tensile strengths, but lower Young's modulus in all samples under consideration. TGA analysis also shows that thermal stability of the nanocomposite, increases in presence of B4C. Finally, neutron absorption analysis shows that increasing the B4C concentration leads to a nonlinearly build-up of neutron absorption cross section.

  14. Friction Stir Welding of Al-B4C Composite Fabricated by Accumulative Roll Bonding: Evaluation of Microstructure and Mechanical Behavior

    Science.gov (United States)

    Moradi Faradonbeh, Alireza; Shamanian, Morteza; Edris, Hossein; Paidar, Moslem; Bozkurt, Yahya

    2018-01-01

    In this investigation, friction stir welding (FSW) of Al-B4C composite fabricated by 10 cycles accumulative roll bonding was conducted. In order to investigate the influences of pin geometry on microstructure and mechanical properties, four different pin geometries (cylindrical, square, triangular and hexagonal) were selected. It was found that FSW parameters had a major effect on the fragmentation and distribution of reinforcement particles in stir zone. When the tool travel speed was increased, the distribution of B4C particles was become gradually uniform in the aluminum matrix. The effect of tool rotational speed on the peak temperature was determined to be greater than the tool travel speed. The attained data of tensile properties and microhardness tests showed that the tool travel speed had bilateral effect on the tensile strength. The maximum tensile joint efficiency was obtained as 238% for FSWed of Al-2%B4C composite to annealed base Al sheet.

  15. Evolution of Diterpene Metabolism: Sitka Spruce CYP720B4 Catalyzes Multiple Oxidations in Resin Acid Biosynthesis of Conifer Defense against Insects1[C][W][OA

    Science.gov (United States)

    Hamberger, Björn; Ohnishi, Toshiyuki; Hamberger, Britta; Séguin, Armand; Bohlmann, Jörg

    2011-01-01

    Diterpene resin acids (DRAs) are specialized (secondary) metabolites of the oleoresin defense of conifers produced by diterpene synthases and cytochrome P450s of the CYP720B family. The evolution of DRA metabolism shares common origins with the biosynthesis of ent-kaurenoic acid, which is highly conserved in general (primary) metabolism of gibberellin biosynthesis. Transcriptome mining in species of spruce (Picea) and pine (Pinus) revealed CYP720Bs of four distinct clades. We cloned a comprehensive set of 12 different Sitka spruce (Picea sitchensis) CYP720Bs as full-length cDNAs. Spatial expression profiles, methyl jasmonate induction, and transcript enrichment in terpenoid-producing resin ducts suggested a role of CYP720B4 in DRA biosynthesis. CYP720B4 was characterized as a multisubstrate, multifunctional enzyme by the formation of oxygenated diterpenoids in metabolically engineered yeast, yeast in vivo transformation of diterpene substrates, in vitro assays with CYP720B4 protein produced in Escherichia coli, and alteration of DRA profiles in RNA interference-suppressed spruce seedlings. CYP720B4 was active with 24 different diterpenoid substrates, catalyzing consecutive C-18 oxidations in the biosynthesis of an array of diterpene alcohols, aldehydes, and acids. CYP720B4 was most active in the formation of dehydroabietic acid, a compound associated with insect resistance of Sitka spruce. We identified patterns of convergent evolution of CYP720B4 in DRA metabolism and ent-kaurene oxidase CYP701 in gibberellin metabolism and revealed differences in the evolution of specialized and general diterpene metabolism in a gymnosperm. The genomic and functional characterization of the gymnosperm CYP720B family highlights that the evolution of specialized metabolism involves substantial diversification relative to conserved, general metabolism. PMID:21994349

  16. Evolution of diterpene metabolism: Sitka spruce CYP720B4 catalyzes multiple oxidations in resin acid biosynthesis of conifer defense against insects.

    Science.gov (United States)

    Hamberger, Björn; Ohnishi, Toshiyuki; Hamberger, Britta; Séguin, Armand; Bohlmann, Jörg

    2011-12-01

    Diterpene resin acids (DRAs) are specialized (secondary) metabolites of the oleoresin defense of conifers produced by diterpene synthases and cytochrome P450s of the CYP720B family. The evolution of DRA metabolism shares common origins with the biosynthesis of ent-kaurenoic acid, which is highly conserved in general (primary) metabolism of gibberellin biosynthesis. Transcriptome mining in species of spruce (Picea) and pine (Pinus) revealed CYP720Bs of four distinct clades. We cloned a comprehensive set of 12 different Sitka spruce (Picea sitchensis) CYP720Bs as full-length cDNAs. Spatial expression profiles, methyl jasmonate induction, and transcript enrichment in terpenoid-producing resin ducts suggested a role of CYP720B4 in DRA biosynthesis. CYP720B4 was characterized as a multisubstrate, multifunctional enzyme by the formation of oxygenated diterpenoids in metabolically engineered yeast, yeast in vivo transformation of diterpene substrates, in vitro assays with CYP720B4 protein produced in Escherichia coli, and alteration of DRA profiles in RNA interference-suppressed spruce seedlings. CYP720B4 was active with 24 different diterpenoid substrates, catalyzing consecutive C-18 oxidations in the biosynthesis of an array of diterpene alcohols, aldehydes, and acids. CYP720B4 was most active in the formation of dehydroabietic acid, a compound associated with insect resistance of Sitka spruce. We identified patterns of convergent evolution of CYP720B4 in DRA metabolism and ent-kaurene oxidase CYP701 in gibberellin metabolism and revealed differences in the evolution of specialized and general diterpene metabolism in a gymnosperm. The genomic and functional characterization of the gymnosperm CYP720B family highlights that the evolution of specialized metabolism involves substantial diversification relative to conserved, general metabolism.

  17. Microstructure and electrical properties of slug-type resistors based on B4C and TiC - ESCA - XPS and impedance spectroscopy investigations

    International Nuclear Information System (INIS)

    Klimiec, E.; Zaraska, W.; Stobiecki, T.; Bak, W.; Starzyk, F.

    2000-01-01

    The microstructure and electrical properties of slug-type resistors based on B 4 C and TiC were investigated. From XPS measurements was deducted that Ti in TiO 2 is in intermediate oxidation number between Ti +4 and Ti +3 . The impedance of both type of resistors is independent on frequency in the range from 10 3 to 10 4 Hz, only very subtle differences above 10 4 Hz are observed. The metallic type conductivity in TiC and semiconducting in B 4 C was established. (author)

  18. Study on the influence of the B4C layer thickness on the neutron flux and energy distribution shape in multi-electrode ionisation chamber.

    Science.gov (United States)

    Tymińska, K; Maciak, M; Ośko, J; Tulik, P; Zielczyński, M; Gryziński, M A

    2014-10-01

    A model of a multi-electrode ionisation chamber, with polypropylene electrodes coated with a thin layer of B4C was created within Monte Carlo N-Particle Transport Code (MCNPX) and Fluktuierende Kaskade (FLUKA) codes. The influence of the layer thickness on neutron absorption in B4C and on the neutron spectra in the consecutive intra-electrode gas volumes has been studied using the MCNPX and FLUKA codes. The results will be used for designing the new type of the ionisation chamber. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. Mean-field theory for the Tsub(c2)-minimum in the phase diagram of Ersub(1-x)Hosub(x)Rh4B4

    International Nuclear Information System (INIS)

    Schuh, B.; Grewe, N.

    1981-01-01

    The experimentally observed shape of the phase boundary between the superconducting and the ferromagnetically ordered state in the reentrant ferromagnetic superconductor compound Ersub(1-x)Hosub(x)Rh 4 B 4 is explained within a simple Ginsburg-Landau mean field theory as resulting from a competition of two order parameters corresponding to the magnetic Ho- and Er-moments respectively. (author)

  20. Delineation of polar localization domains of Agrobacterium tumefaciens type IV secretion apparatus proteins VirB4 and VirB11.

    Science.gov (United States)

    Das, Aditi; Das, Anath

    2014-10-01

    Agrobacterium tumefaciens transfers DNA and proteins to a plant cell through a type IV secretion apparatus assembled by the VirB proteins. All VirB proteins localized to a cell pole, although these conclusions are in dispute. To study subcellular location of the VirB proteins and to identify determinants of their subcellular location, we tagged two proteins, VirB4 and VirB11, with the visual marker green fluorescent protein (GFP) and studied localization of the fusion proteins by epifluorescence microscopy. Both GFP-VirB4 and GFP-VirB11 fusions localized to a single cell pole. GFP-VirB11 was also functional in DNA transfer. To identify the polar localization domains (PLDs) of VirB4 and VirB11, we analyzed fusions of GFP with smaller segments of the two proteins. Two noncontiguous regions in VirB4, residues 236-470 and 592-789, contain PLDs. The VirB11 PLD mapped to a 69 amino acid segment, residues 149-217, in the central region of the protein. These domains are probably involved in interactions that target the two proteins to a cell pole. © 2014 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  1. 26 CFR 1.367(b)-4T - Acquisition of foreign corporate stock or assets by a foreign corporation in certain...

    Science.gov (United States)

    2010-04-01

    ... (CONTINUED) INCOME TAXES Effects on Corporation § 1.367(b)-4T Acquisition of foreign corporate stock or... treated, under section 318, as indirectly owning 100% of the CFC2 stock after the transaction, under... section 318, as indirectly owning 100% of CFC2 after the transaction, section 302(a) does not apply to the...

  2. Oxazolone Versus Macrocycle Structures for Leu-Enkephalin b(2)-b(4): Insights from Infrared Multiple-Photon Dissociation Spectroscopy and Gas-Phase Hydrogen/Deuterium Exchange

    NARCIS (Netherlands)

    Chen, X. A.; Steill, J. D.; Oomens, J.; Pollfer, N. C.

    2010-01-01

    The collision-induced dissociation (CID) products b(2)-b(4) from Leu-enkephalin are examined with infrared multiple-photon dissociation (IR-MPD) spectroscopy and gas-phase hydrogen/deuterium exchange (HDX). Infrared spectroscopy reveals that b(2) exclusively adopts oxazolone structures, protonated

  3. Impact of B4C capping layer for extreme ultraviolet mask on the sensitivity of patterned mask inspection using a projection electron microscope

    Science.gov (United States)

    Iida, Susumu; Hirano, Ryoichi; Amano, Tsuyoshi; Watanabe, Hidehiro

    2014-10-01

    The inspection sensitivity of a patterned extreme ultraviolet mask with B4C-capped multilayer (ML) was investigated using a simulated projection electron microscope (PEM) image. Extrusion and intrusion defects with 16-nm size were detected with their intensity of >10 times the standard deviation of the background level on a half-pitch 64-nm line-and-space pattern. The defect detection sensitivity in this case was higher than that of a Ru-capped ML sample and has a potential to meet the requirement for beyond 16-nm node generation from the standpoint of patterned mask inspection using the PEM technique. These results indicate that the B4C capping layer, besides its good durability, has an advantage for high sensitivity of patterned mask inspection. The optimal condition of the incident beam energy was found to be 500 and 1,000 eV for the samples of B4C-capped ML and B4C-buffered Ru-capped ML, respectively. The sensitivity of defect detection was strongly affected by the difference of secondary electron emission coefficients (SEECs) between the absorber layer and capping layer. However, the small incident beam energy was found to be preferable when the SEEC difference was relatively high.

  4. Impact of B4C capping layer for EUV mask on the sensitivity of patterned mask inspection using projection electron microscope

    Science.gov (United States)

    Iida, Susumu; Hirano, Ryoichi; Amano, Tsuyoshi; Watanabe, Hidehiro

    2014-10-01

    The inspection sensitivity of a patterned extreme ultraviolet (EUV) mask with B4C capped multilayer (ML) was investigated using a simulated projection electron microscope (PEM) image. Extrusion and intrusion defects with 16 nm in size were detected with their intensity of > 10 times the standard deviation of the background level on a half-pitch (hp) 64 nm line and space pattern. The defect detection sensitivity in this case was higher than that of Ru capped ML sample, and has a potential to meet the requirement for beyond 16 nm node generation from the standpoint of patterned mask inspection using the PEM technique. These results indicate that B4C capping layer besides its good durability has an advantage for high sensitivity of patterned mask inspection. The optimal condition of the incident beam energy was found to be 500 and 1000 eV for the samples of B4C capped ML and B4C buffered Ru capped ML, respectively. The sensitivity of defect detection was strongly affected by the difference of secondary electron emission coefficients (SEECs) between the absorber layer and capping layer. However, severely scattered electrons near the pattern edge become a source of noise and then they block the effect of large SEEC difference. Thus, the small incident beam energy was found to be preferable when the SEEC difference was relatively high.

  5. Stratification by Smoking Status Reveals an Association of CHRNA5-A3-B4 Genotype with Body Mass Index in Never Smokers

    NARCIS (Netherlands)

    Taylor, A.E.; Morris, R.W.; Fluharty, M.E.; Bjorngaard, J.H.; Asvold, B.O.; Gabrielsen, M.E.; Campbell, A.; Marioni, R.; Kumari, M.; Hällfors, J.; Männistö, S.; Marques-Vidal, P.; Kaakinen, M.; Cavadino, A.; Postmus, I.; Husemoen, L.L.N.; Skaaby, T.; Ahluwalia, T.S.; Treur, J.L.; Willemsen, G.; Dale, C.; Wannamethee, S.G.; Lahti, J.; Palotie, A.; Räikkönen, K.; Kisialiou, A.; McConnachie, A.; Padmanabhan, S.; Wong, A.; Dalgard, C.; Paternoster, L.; Ben-Shlomo, Y.; Tyrrell, J.; Horwood, L.J.; Fergusson, D.; Kennedy, M.A.; Frayling, T.M.; Nohr, E.A.; Christiansen, L.; Ohm Kyvik, K.; Kuh, D; Watt, G.; Eriksson, J.; Whincup, P.H.; Vink, J.M.; Boomsma, D.I.; Davey Smith, G.; Lawlor, D.; Linneberg, A.; Ford, I.; Jukema, J.W.; Power, C.; Hyppönen, E.; Järvelin, M.R.; Preisig, M.; Borodulin, K.; Kaprio, J.; Kivimaki, M.; Smith, B.H.; Hayward, C.; Romundstad, P.R.; Sørensen, T.I.A.; Munafo, M.R.; Sattar, N.

    2014-01-01

    We previously used a single nucleotide polymorphism (SNP) in the CHRNA5-A3-B4 gene cluster associated with heaviness of smoking within smokers to confirm the causal effect of smoking in reducing body mass index (BMI) in a Mendelian randomisation analysis. While seeking to extend these findings in a

  6. Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers

    NARCIS (Netherlands)

    Taylor, A.E.; Morris, R.W.; Fluharty, M.E.; Björngaard, J.H.; Asvold, B.A.; Gabrielsen, M.E.; Campbell, A.; Marioni, R.E.; Kumari, M.; Hallfors, J.; Mannisto, S.; Marques-Vidal, P.; Kaakinen, M.; Cavadino, A.; Postmus, I.; Husemoen, L.L.N.; Skaaby, T.; Ahluwalia, T.V.S.; Treur, J.L.; Willemsen, G.; Dale, C.E.; Wannamethee, S.G.; Lahti, J.; Palotie, A.; Raikkonen, K.; Kisialiou, A.; McConnachie, A.; Padmanabhan, S.; Wong, A.; Dalgard, C.; Paternoster, L.; Ben-Shlomo, Y.; Tyrrell, J.; Horwood, J.; Fergusson, D.M.; Kennedy, M.A.; Frayling, T.; Nohr, E.A.; Christiansen, L.; Kyvik, K.O.; Kuh, D.; Watt, G.; Eriksson, J.; Whincup, P.H.; Vink, J.M.; Boomsma, D.I.; Smith, G.D.; Lawlor, D.A.; Linneberg, A.; Ford, I.; Jukema, J.W.; Power, C.; Hypponen, E.; Jarvelin, M.R.; Preisig, M.; Borodulin, K.; Kaprio, J.; Kivimaki, M.; Smith, B.H.; Hayward, C.; Romundstad, P.R.; Sorensen, T.I.A.; Munafò, M.R.; Sattar, N.

    2014-01-01

    We previously used a single nucleotide polymorphism (SNP) in the CHRNA5-A3-B4 gene cluster associated with heaviness of smoking within smokers to confirm the causal effect of smoking in reducing body mass index (BMI) in a Mendelian randomisation analysis. While seeking to extend these findings in a

  7. Mapping of interaction between cytochrome P450 2B4 and cytochrome b5: the first evidence of two mutual orientations

    Czech Academy of Sciences Publication Activity Database

    Šulc, Miroslav; Ječmen, Tomáš; Šnajdrová, Renata; Novák, Petr; Martínek, V.; Hodek, P.; Stiborová, M.; Hudeček, J.

    2012-01-01

    Roč. 33, č. 3 (2012), s. 101-107 ISSN 0172-780X R&D Projects: GA ČR(CZ) GAP207/12/0627 Institutional support: RVO:61388971 Keywords : cytochrome P450 2B4 * protein-protein interaction * mass spectrometry Subject RIV: CE - Biochemistry Impact factor: 0.932, year: 2012

  8. Heat treatment effect on the microstructure, tensile properties and dry sliding wear behavior of A356-10%B4C cast composites

    International Nuclear Information System (INIS)

    Lashgari, H.R.; Zangeneh, Sh.; Shahmir, H.; Saghafi, M.; Emamy, M.

    2010-01-01

    In present paper, an attempt was made to examine the influence of T6 heat treatment (solution treatment at 540 o C for 5 h, quenching in hot water and artificial aging at 170 o C for 8 h) on the microstructure, tensile properties and dry sliding wear behavior of A356-10%B 4 C cast composites. The composite ingots were made by stir casting process. In this work, the matrix alloy and composite were characterized by optical microscope, scanning electron microscope equipped with energy dispersive X-ray spectroscopy, tensile tests and conventional pin-on-disk experiment. The obtained results showed that in Al-B 4 C composite, T6 treatment was a dominant factor on the hardness improvement in comparison with hardness increasing due to the addition of B 4 C hard particles. In addition, T6 treatment can contribute to the strong bonding between B 4 C and matrix alloy and also it can change eutectic silicon morphology from acicular to near spherical. This case can lead to higher strength and wear properties of heat treated metal matrix composites in comparison with unheat treated state. Observation of worn surfaces indicated detachment of mechanically mixed layer which can primarily due to the delamination wear mechanism under higher applied load.

  9. Induction of the PDH bypass and upregulation of the ALDH7B4 in plants treated with herbicides inhibiting amino acid biosynthesis.

    Science.gov (United States)

    Gil-Monreal, Miriam; Zabalza, Ana; Missihoun, Tagnon D; Dörmann, Peter; Bartels, Dorothea; Royuela, Mercedes

    2017-11-01

    Imazamox and glyphosate represent two classes of herbicides that inhibit the activity of acetohydroxyacid synthase in the branched-chain amino acid biosynthesis pathway and the activity of 5-enolpyruvylshikimate-3-phosphate synthase in the aromatic amino acid biosynthesis pathway, respectively. However, it is still unclear how imazamox and glyphosate lead to plant death. Both herbicides inhibit amino-acid biosynthesis and were found to induce ethanol fermentation in plants, but an Arabidopsis mutant deficient in alcohol dehydrogenase 1 was neither more susceptible nor more resistant than the wild-type to the herbicides. In this study, we investigated the effects of the amino acid biosynthesis inhibitors, imazamox and glyphosate, on the pyruvate dehydrogenase bypass reaction and fatty acid metabolism in A. thaliana. We found that the pyruvate dehydrogenase bypass was upregulated following the treatment by the two herbicides. Our results suggest that the Arabidopsis aldehyde dehydrogenase 7B4 gene might be participating in the pyruvate dehydrogenase bypass reaction. We evaluated the potential role of the aldehyde dehydrogenase 7B4 upon herbicide treatment in the plant defence mechanism. Plants that overexpressed the ALDH7B4 gene accumulated less soluble sugars, starch, and fatty acids and grew better than the wild-type after herbicide treatment. We discuss how the upregulation of the ALDH7B4 alleviates the effects of the herbicides, potentially through the detoxification of the metabolites produced in the pyruvate dehydrogenase bypass. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers

    DEFF Research Database (Denmark)

    Taylor, Amy E; Morris, Richard W; Fluharty, Meg E

    2014-01-01

    We previously used a single nucleotide polymorphism (SNP) in the CHRNA5-A3-B4 gene cluster associated with heaviness of smoking within smokers to confirm the causal effect of smoking in reducing body mass index (BMI) in a Mendelian randomisation analysis. While seeking to extend these findings in...

  11. Lack of Associations of CHRNA5-A3-B4 Genetic Variants with Smoking Cessation Treatment Outcomes in Caucasian Smokers despite Associations with Baseline Smoking.

    Directory of Open Access Journals (Sweden)

    Rachel F Tyndale

    Full Text Available CHRNA5-A3-B4 variants, rs16969968, rs588765 and rs578776, are consistently associated with tobacco consumption among smokers, but the association with smoking cessation is less consistent. Among the studies that reported significant associations with cessation, the effects were observed in smokers treated with placebo treatment in some studies and conversely in those receiving active pharmacological therapy (bupropion and nicotine replacement therapies in others. Thus, it remains unclear whether CHRNA5-A3-B4 is a useful marker for optimizing smoking cessation. Using data from 654 Caucasian smokers treated with placebo, nicotine patch or varenicline, we investigated whether CHRNA5-A3-B4 variants were associated with smoking cessation outcomes, and whether there were significant genotype-by-treatment or haplotype-by-treatment interactions. We observed no significant associations between CHRNA5-A3-B4 variants and smoking cessation, despite replicating previous associations with baseline tobacco consumption. At end of treatment the effect size on smoking cessation in the placebo, patch and varenicline groups for rs16969968 [GG vs. GA+AA] was OR = 0.66 (P = 0.23, OR = 1.01 (P = 0.99, and OR = 1.30 (P = 0.36 respectively, of rs588765 [CC vs. CT+TT] was OR = 0.96 (P = 0.90, OR = 0.84 (P = 0.58, and OR = 0.74 (P = 0.29 respectively, and for rs578776 [GG vs. GA+AA] on smoking cessation was OR = 1.02 (P = 0.95, OR = 0.75 (P = 0.35, and OR = 1.20 (P = 0.51 respectively. Furthermore, we observed no associations with cessation using the CHRNA5-A3-B4 haplotype (constructed using rs16969968 and rs588765, nor did we observe any significant genotype-by-treatment interactions, with or without adjusting for the rate of nicotine metabolism (all P>0.05. We also observed no significant genetic associations with 6 month or 12 month smoking abstinence. In conclusion, we found no association between CHRNA5-A3-B4 variants and smoking cessation rates in this clinical

  12. Dry sliding tribological behavior and mechanical properties of Al2024–5 wt.%B4C nanocomposite produced by mechanical milling and hot extrusion

    International Nuclear Information System (INIS)

    Abdollahi, Alireza; Alizadeh, Ali; Baharvandi, Hamid Reza

    2014-01-01

    Highlights: • Nanostructured Al2024 and Al2024–B 4 C nanocomposite prepared via mechanical milling. • The milled powders formed by hot pressing and then exposed to hot extrusion. • Tribological behavior and mechanical properties of samples were investigated. • Al2024–B 4 C nanocomposite showed a better wear resistance and mechanical properties. - Abstract: In this paper, tribological behavior and mechanical properties of nanostructured Al2024 alloy produced by mechanical milling and hot extrusion were investigated before and after adding B 4 C particles. Mechanical milling was used to synthesize the nanostructured Al2024 in attrition mill under argon atmosphere up to 50 h. A similar process was used to produce Al2024–5 wt.%B 4 C composite powder. The milled powders were formed by hot pressing and then were exposed to hot extrusion in 750 °C with extrusion ratio of 10:1. To study the microstructure of milled powders and hot extruded samples, optical microscopy, transmission electron microscopy and scanning electron microscopy (SEM) equipped with an energy dispersive X-ray spectrometer (EDS) were used. The mechanical properties of samples were also compared together using tension, compression and hardness tests. The wear properties of samples were studied using pin-on-disk apparatus under a 20 N load. The results show that mechanical milling decreases the size of aluminum matrix grains to less than 100 nm. The results of mechanical and wear tests also indicate that mechanical milling and adding B 4 C particles increase strength, hardness and wear resistance of Al2024 and decrease its ductility remarkably

  13. Upregulation of epidermal growth factor receptor 4 in oral leukoplakia

    Science.gov (United States)

    Kobayashi, Hiroshi; Kumagai, Kenichi; Gotoh, Akito; Eguchi, Takanori; Yamada, Hiroyuki; Hamada, Yoshiki; Suzuki, Satsuki; Suzuki, Ryuji

    2013-01-01

    In the present study, we investigate the expression profile of the epidermal growth factor receptor family, which comprises EGFR/ErbB1, HER2/ErbB2, HER3/ErbB3 and HER4/ErbB4 in oral leukoplakia (LP). The expression of four epidermal growth factor receptor (EGFR) family genes and their ligands were measured in LP tissues from 14 patients and compared with levels in 10 patients with oral lichen planus (OLP) and normal oral mucosa (NOM) from 14 healthy donors by real-time polymerase chain reaction (PCR) and immunohistochemistry. Synchronous mRNA coexpression of ErbB1, ErbB2, ErbB3 and ErbB4 was detected in LP lesions. Out of the receptors, only ErbB4 mRNA and protein was more highly expressed in LP compared with NOM tissues. These were strongly expressed by epithelial keratinocytes in LP lesions, as shown by immunohistochemistry. Regarding the ligands, the mRNA of Neuregulin2 and 4 were more highly expressed in OLP compared with NOM tissues. Therefore, enhanced ErbB4 on the keratinocytes and synchronous modulation of EGFR family genes may contribute to the pathogenesis and carcinogenesis of LP. PMID:23492901

  14. Near-net shape manufacture of B4C–Co and ZrC–Co composites by slip casting and pressureless sintering

    DEFF Research Database (Denmark)

    Ortiz, Angel L.; Leal, Victor Manuel Candelario; Moreno, Rodrigo

    2017-01-01

    Fabrication of near-net shaped B4C–Co and ZrC–Co composites by slip casting and pressureless sintering is described. It is shown how B4C–Co and ZrC–Co concentrated suspensions can be prepared by aqueous colloidal processing, and optimized (in terms of pH, deflocculant contents, and sonication time......) to have a shear-thinning rheological behaviour suitable for the near-net shaping of the corresponding cermet compacts by slip casting. It is also demonstrated that the robust, highly-dense compacts so obtained have a uniform green microstructure without macro-defects or gradient density, and which can...... is given for these observations, and general implications are discussed for the near-net shape manufacture of these and similar carbide-metal composites for use in engineering applications....

  15. Investigation of the microstructure of Ni and B4C ceramic-metal mixtures obtained by cold spray coating and followed by laser cladding

    Science.gov (United States)

    Filippov, A. A.; Fomin, V. M.; Orishich, A. M.; Malikov, A. G.; Ryashin, N. S.; Golyshev, A. A.

    2017-10-01

    In the present work, a combined method is considered for the production of a metal-matrix composite coating based on Ni and B4C. The coating is created by consistently applied methods: cold spray and laser cladding. Main focus of this work aimed to microstructure of coatings, element content and morphology of laser tracks. At this stage, the authors focused on the interaction of the laser unit with the substance without affecting the layer-growing technology products. It is shown that coating has deformed particles of nickel and the significantly decreased content of ceramic particles B4C after cold spray. After laser cladding there are no boundaries between nickel and dramatically changes in ceramic particles.

  16. Optical properties of boron carbide near the boron K edge evaluated by soft-x-ray reflectometry from a Ru/B(4)C multilayer.

    Science.gov (United States)

    Ksenzov, Dmitriy; Panzner, Tobias; Schlemper, Christoph; Morawe, Christian; Pietsch, Ullrich

    2009-12-10

    Soft-x-ray Bragg reflection from two Ru/B(4)C multilayers with 10 and 63 periods was used for independent determination of both real and imaginary parts of the refractive index n = 1 - delta + ibeta close to the boron K edge (approximately 188 eV). Prior to soft x-ray measurements, the structural parameters of the multilayers were determined by x-ray reflectometry using hard x rays. For the 63-period sample, the optical properties based on the predictions made for elemental boron major deviations were found close to the K edge of boron for the 10-period sample explained by chemical bonding of boron to B(4)C and various boron oxides.

  17. Exome sequencing identified rare variants in genes HSPG2 and ATP2B4 in a family segregating developmental dysplasia of the hip.

    Science.gov (United States)

    Basit, Sulman; Albalawi, Alia M; Alharby, Essa; Khoshhal, Khalid I

    2017-03-21

    Developmental dysplasia of the hip (DDH) is a common pathological condition of the musculoskeletal system in infants which results in a congenital and developmental malformation of the hip joint. DDH is a spectrum of pathologies affecting the infant hip ranging from asymptomatic subtle radiographic signs through mild instability to frank dislocations with acetabular dysplasia. A Saudi family with three affected individuals with DDH was identified and genetic analysis was performed to detect the possible genetic defect(s) underlying DDH in the affected members of the family. We performed whole genome genotyping using Illumina HumanOmni 2.5 M array and whole exome sequencing (WES) using Nextera Rapid capture kit and Illumina NextSeq500 instrument in four individuals of a family with DDH. SNP data analysis did not identify any runs of homozygosity and copy number variations. Identity-by-descent (IBD) analysis on whole genome genotyping data identified a shared haplotypes on chromosome 1 in affected individuals. An analysis of the WES data identified rare heterozygous variants in HSPG2 and ATP2B4 genes in the affected individuals. Multiple prediction software predicted that the variants identified are damaging. Moreover, in silico analysis showed that HSPG2 regulates ATP2B4 expression using a variety of transcription factors. Our results indicate that there might be a functional epistatic interaction between HSPG2 and ATP2B4, and DDH in the family studied is due to a combined effect of both variants. These variants are also present in the asymptomatic mother suggesting that the variants in HSPG2 and ATP2B4 are incompletely penetrant. This study provides the first evidence of digenic inheritance of DDH in a family and extends the spectrum of genetic heterogeneity in this human disorder.

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

    Directory of Open Access Journals (Sweden)

    José Wander BREGANÓ

    2014-09-01

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

  19. The role of anti-NHba antibody in bactericidal activity elicited by the meningococcal serogroup B vaccine, MenB-4C.

    Science.gov (United States)

    Partridge, Elizabeth; Lujan, Eduardo; Giuntini, Serena; Vu, David M; Granoff, Dan M

    2017-07-24

    MenB-4C (Bexsero®) is a multicomponent serogroup B meningococcal vaccine. For vaccine licensure, efficacy was inferred from serum bactericidal antibody (SBA) against three antigen-specific indicator strains. The bactericidal role of antibody to the fourth vaccine antigen, Neisserial Heparin binding antigen (NHba), is incompletely understood. We identified nine adults immunized with two or three doses of MenB-4C who had sufficient volumes of sera and >3-fold increases in SBA titer against a strain with high NHba expression, which was mismatched with the other three MenB-4C antigens that elicit SBA. Using 1month-post-immunization sera we measured the effect of depletion of anti-NHba and/or anti-Factor H binding protein (FHbp) antibodies on SBA. Against three strains matched with the vaccine only for NHba, depletion of anti-NHba decreased SBA titers by an average of 43-79% compared to mock-adsorbed sera (Pvaccine antigen), depletion of anti-FHbp antibodies also decreased SBA by 45-64% (Pvaccine antigen, depletion of anti-NHba decreased SBA by an average of 26%, compared to mock-adsorbed sera (Panti-FHbp antibody decreased SBA by 92% (PAnti-NHba antibody can contribute to SBA elicited by MenB-4C, particularly in concert with anti-FHbp antibody. However, some high NHba-expressing strains are resistant, even with an exact match between the amino acid sequence of the vaccine and strain antigens. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Redefining the progeroid form of Ehlers-Danlos syndrome: report of the fourth patient with B4GALT7 deficiency and review of the literature.

    Science.gov (United States)

    Guo, Michael H; Stoler, Joan; Lui, Julian; Nilsson, Ola; Bianchi, Diana W; Hirschhorn, Joel N; Dauber, Andrew

    2013-10-01

    Proteoglycans are a component of the extracellular matrix and are critical for cellular and tissue function. Mutations in proteoglycan components and enzymes involved in proteoglycan synthesis have been implicated in several growth disorders, with common features including short stature and skeletal dysplasia. For example, mutations in B4GALT7, a gene whose protein product catalyzes proteoglycan synthesis, have been associated with the rare progeroid variant of Ehlers-Danlos syndrome. Here, we conducted exome sequencing in a patient with a previously undiagnosed growth disorder and identified compound heterozygous mutations in B4GALT7. This patient is just the fourth individual with genetically confirmed progeroid variant of Ehlers-Danlos syndrome. The mutations include a previously characterized c.808C>T p.Arg270Cys substitution, and a novel c.122T>C p.Leu41Pro substitution. We demonstrate that the novel mutation caused decreased levels of the enzyme, supporting the pathogenicity of the mutation. Our report identifies a novel mutation in B4GALT7 causing the progeroid variant of Ehlers-Danlos syndrome and contributes an extensive phenotypic characterization of a patient with the syndrome. We also reviewed the previous literature in addition to the present patient, and conclude that the key features associated with B4GALT7 deficiency are short stature, developmental anomalies of the forearm bones and elbow, and bowing of the extremities, in addition to the classic features of Ehlers-Danlos syndrome. This report helps define the phenotype of the progeroid variant of Ehlers-Danlos syndrome and furthers our understanding of the effect of proteoglycan defects in growth disorders. Copyright © 2013 Wiley Periodicals, Inc.

  1. Isolation and characterization of CYP6B4, a furanocoumarin-inducible cytochrome P450 from a polyphagous caterpillar (Lepidoptera:papilionidae).

    Science.gov (United States)

    Hung, C F; Berenbaum, M R; Schuler, M A

    1997-05-01

    Papilio glaucus (tiger swallowtail) is a generalist that rarely encounters plants containing furanocoumarins yet is constitutively capable of metabolizing low levels of these highly toxic allelochemicals. In larvae of this species, metabolism of linear (xanthotoxin, bergapten), and angular (angelicin, sphondin), furanocoumarins can be induced up to 30-fold by the presence of xanthotoxin in their diet. Degenerate primers corresponding to conserved amino acid sequences in three insect P450s, Musca domestica (CYP6A1), Drosophila melanogaster (CYP6A2) and Papilio polyxenes (CYP6B1), were used to clone xanthotoxin-induced P450 transcripts from P. glaucus larvae by a reverse transcription-polymerase chain reaction (RT-PCR) strategy. Positive clones encoding the highly conserved F--G-R-C-G P450 signature motif were used to isolate a full-length CYP6B4v1 cDNA from a P. glaucus xanthotoxin-induced cDNA library. Sequence comparisons indicate the P. glaucus CYP6B4v1 protein sequence is 63% and 61% identical, respectively, to the P. polyxenes furanocoumarin-inducible CYP6B1v1 and CYP6B3v1 proteins. Northern analysis indicates that CYP6B4 and related transcripts are highly induced in response to xanthotoxin. Baculovirus-mediated expression of the CYP6B4v1 protein in lepidopteran cell lines demonstrates that this P450 isozyme metabolizes isopimpinellin, imperatorin, and bergapten at high rates, xanthotoxin and psoralen at intermediate rates and angelicin, sphondin, and trioxsalen only at very low rates.

  2. Mixing thermodynamic properties of 1-butyl-4-methylpyridinium tetrafluoroborate [b4mpy][BF{sub 4}] with water and with an alkan-1ol (methanol to pentanol)

    Energy Technology Data Exchange (ETDEWEB)

    Ortega, J. [Laboratorio de Termodinamica y Fisicoquimica de Fluidos, Parque Cientifico-Tecnologico, Campus Universitario de Tafira, Universidad de Las Palmas de Gran Canaria, 35071-Las Palmas de Gran Canaria, Canary Islands (Spain)], E-mail: jortega@dip.ulpgc.es; Vreekamp, R.; Penco, E.; Marrero, E. [Laboratorio de Termodinamica y Fisicoquimica de Fluidos, Parque Cientifico-Tecnologico, Campus Universitario de Tafira, Universidad de Las Palmas de Gran Canaria, 35071-Las Palmas de Gran Canaria, Canary Islands (Spain)

    2008-07-15

    This article presents a study of the behaviour in solution of 1-butyl-4-methylpyridinium tetrafluoroborate [b4mpy][BF{sub 4}] in water and in the first five alkanols of the series methanol to pentan-1-ol. The excess enthalpies, H{sub m}{sup E} and volumes, V{sub m}{sup E} were determined at the temperatures (298.15 and 318.15) K. At these temperatures, the [b4mpy][BF{sub 4}] was completely miscible in water, methanol, and ethanol, but only partially miscible in the other alkanols. A solubility study was carried out and the (liquid + liquid) equilibria of the ([b4mpy][BF{sub 4}] + alkanol) systems were experimentally determined, evaluating zones of complete miscibility and determining the UCST in each case. The mixtures with water gave positive values of H{sub m}{sup E} and V{sub m}{sup E}, being also positive the changes of these quantities with temperature. The mixtures with alkanols gave values of H{sub m}{sup E}>0 and V{sub m}{sup E}<0, and for these binary mixtures (dH{sub m}{sup E}/dT){sub p}>0 and (dV{sub m}{sup E}/dT){sub p}<0. For all cases, results were interpreted and compared with data obtained in mixtures with another isomer [b3mpy][BF{sub 4}]. Excess properties were correlated with a suitable equation and the area and volume parameters were calculated for [b4mpy][BF{sub 4}].

  3. A Comparative Study on SiC-B4C-Si Cermet Prepared by Pressureless Sintering and Spark Plasma Sintering Methods

    Science.gov (United States)

    Sahani, P.; Karak, S. K.; Mishra, B.; Chakravarty, D.; Chaira, D.

    2016-06-01

    Silicon carbide (SiC)-boron carbide (B4C) based cermets were doped with 5, 10, and 20 wt pct Silicon (Si) and their sinterability and properties were investigated for conventional sintering at 2223 K (1950 °C) and spark plasma sintering (SPS) at 1623 K (1350 °C). An average particle size of ~3 µm was obtained after 10 hours of milling. There is an enhancement of Vickers microhardness in the 10 wt pct Si sample from 18.10 in conventional sintering to 27.80 GPa for SPS. The relative density, microhardness, and indentation fracture toughness of the composition SiC60(B4C)30Si10 fabricated by SPS are 98 pct, 27.80 GPa, and 3.8 MPa m1/2, respectively. The novelty of the present study is to tailor the wettability and ductility of the cermet by addition of Si into the SiC-B4C matrix. Better densification with improved properties is achieved for cermets consolidated by SPS at lower temperatures than conventional sintering.

  4. Energy transfer in Pr3+ and Mn2+ co-doped SrB6O10 and SrB4O7

    International Nuclear Information System (INIS)

    Chen Yonghu; Yan Wuzhao; Shi Chaoshu

    2007-01-01

    The luminescent properties of Pr 3+ and Mn 2+ -doped SrB 6 O 10 and SrB 4 O 7 powder samples were investigated from the point of view of energy transfer between Pr 3+ and Mn 2+ . The emission from the 1 S 0 level of Pr 3+ was found in the SrB 6 O 10 :Pr 3+ sample as well as in the SrB 4 O 7 :Pr 3+ sample, indicating the 1 S 0 level is below the lowest 4f5d energy level in these hosts. The spectral overlaps between the emission spectra of Pr 3+ -doped samples and the excitation spectra of Mn 2+ -doped sample were found in both kinds of strontium borates. These spectral overlaps are in favor of the energy transfer from Pr 3+ to Mn 2+ . However, in the emission spectra of the SrB 6 O 10 :Pr 3+ , Mn 2+ , no indication of energy transfer was observed, though the emission spectra of SrB 4 O 7 :Pr 3+ , Mn 2+ did show evidence of energy transfer from Pr 3+ to Mn 2+ . The possible reasons were discussed

  5. A Tri-modal 2024 Al -B4C composites with super-high strength and ductility: Effect of coarse-grained aluminum fraction on mechanical behavior

    Directory of Open Access Journals (Sweden)

    Alireza Abdollahi

    2014-12-01

    Full Text Available In this study, ultrafine grained 2024 Al alloy based B4C particles reinforced composite was produced by mechanical milling and hot extrusion. Mechanical milling was used to synthesize the nanostructured Al2024 in attrition mill under argon atmosphere up to 50h. A similar process was used to produce Al2024-5%wt. B4C composite powder. To produce trimodal composites, milled powders were combined with coarse grained aluminum in 30 and 50 wt% and then were exposed to hot extrusion at 570°C. The microstructure of hot extruded samples were studied by optical microscope, Transmission electron microscope (TEM and scanning electron microscope (SEM equipped with EDS spectroscopy. The mechanical properties of samples were compared by using tensile, compression and hardness tests. The results showed that the strength, after 50 h milling and addition of 5wt% B4C, increased from 340 to 582 MPa and the hardness increased from 87 HBN to 173 HBN, but the elongation decreased from 14 to 0.5%. By adding the coarse-grained aluminum powder, the strength and hardness decreased slightly, but the increases in return. Ductility increase is the result of increase in dislocation movements and strength increase is the result of restriction in plastic deformation by nanostructured regions. Furthermore, the strength and hardness of trimodal composites were higher, but their ductility was lower.

  6. Effect of detergent binding on cytochrome P450 2B4 structure as analyzed by X-ray crystallography and deuterium-exchange mass spectrometry.

    Science.gov (United States)

    Shah, Manish B; Jang, Hyun-Hee; Wilderman, P Ross; Lee, David; Li, Sheng; Zhang, Qinghai; Stout, C David; Halpert, James R

    2016-09-01

    Multiple crystal structures of CYP2B4 have demonstrated the binding of the detergent 5-cyclohexyl-1-pentyl-β-D-maltoside (CYMAL-5) in a peripheral pocket located adjacent to the active site. To explore the consequences of detergent binding, X-ray crystal structures of the peripheral pocket mutant CYP2B4 F202W were solved in the presence of hexaethylene glycol monooctyl ether (C8E6) and CYMAL-5. The structure in the presence of CYMAL-5 illustrated a closed conformation indistinguishable from the previously solved wild-type. In contrast, the F202W structure in the presence of C8E6 revealed a detergent molecule that coordinated the heme-iron and extended to the protein surface through the substrate access channel 2f. Despite the overall structural similarity of these detergent complexes, remarkable differences were observed in the A, A', and H helices, the F-G cassette, the C-D and β4 loop region. Hydrogen-deuterium exchange mass spectrometry (DXMS) was employed to probe these differences and to test the effect of detergents in solution. The presence of either detergent increased the H/D exchange rate across the plastic regions, and the results obtained by DXMS in solution were consistent in general with the relevant structural snapshots. The study provides insight into effect of detergent binding and the interpretation of associated conformational dynamics of CYP2B4. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Production of Al-Ti-B grain refining master alloys from Na2B4O7 and K2TiF6

    International Nuclear Information System (INIS)

    Birol, Yuecel

    2008-01-01

    It is very desirable to replace the KBF 4 salt in the popular 'halide salt' process to reduce the volume of fluoride salts to be added to molten aluminium in the production of Al-Ti-B grain refiners. Being over 2 times richer in B, Na 2 B 4 O 7 is a promising replacement for KBF 4 , and is used in the present work to produce Al-Ti-B grain refiner master alloys. A fraction of the aluminide particles were entrapped in the spent salt giving a relatively lower Ti recovery when KBF 4 was replaced by Na 2 B 4 O 7 . The grain refining performance of the Al-Ti-B grain refiner alloy thus produced was nevertheless acceptable. The spent salt became too viscous with the oxides, aluminides and borides to be removed by decanting when Na 2 B 4 O 7 .5H 2 O was used to supply boron. The viscous spent salt, entrained in the grain refiner alloy, did not only impair its performance, but also hurt the fluidity of the molten alloy and made pouring difficult

  8. Validation of the FACT-B+4-UL questionnaire and exploration of its predictive value in women submitted to surgery for breast cancer.

    Science.gov (United States)

    Andrade Ortega, Juan Alfonso; Millán Gómez, Ana Pilar; Ribeiro González, Marisa; Martínez Piró, Pilar; Jiménez Anula, Juan; Sánchez Andújar, María Belén

    2017-06-21

    The early detection of upper limb complications is important in women operated on for breast cancer. The "FACT-B+4-UL" questionnaire, a specific variant of the Functional Assessment of Cancer Therapy-Breast (FACT-B) is available among others to measure the upper limb function. The Spanish version of the upper limb subscale of the FACT-B+4 was validated in a prospective cohort of 201 women operated on for breast cancer (factor analysis, internal consistency, test-retest reliability, construct validity and sensitivity to change were determined). Its predictive capacity of subsequent lymphoedema and other complications in the upper limb was explored using logistic regression. This subscale is unifactorial and has a great internal consistency (Cronbach's alpha: 0.87), its test-retest reliability and construct validity are strong (intraclass correlation coefficient: 0.986; Pearson's R with "Quick DASH": 0.81) as is its sensitivity to change. It didn't predict the onset of lymphedema. Its predictive capacity for other upper limb complications is low. FACT-B+4-UL is useful in measuring upper limb disability in women surgically treated for breast cancer; but it does not predict the onset of lymphoedema and its predictive capacity for others complications in the upper limb is low. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  9. Resolving the titer of murine cytomegalovirus by plaque assay using the M2-10B4 cell line and a low viscosity overlay

    Science.gov (United States)

    2014-01-01

    Background Murine cytomegalovirus (MCMV) is increasingly used as an infectious model to investigate host-pathogen interactions in mice. Detailed methods have been published for using primary murine embryonic fibroblasts (MEFs) for preparing stocks and determining viral titers of MCMV. For determining the titer of MCMV by plaque assay, these methods rely on a high viscosity media that restricts viral spreading through the supernatant of the culture, but is also usually too viscous to pipet. Moreover, MEFs must be repeatedly generated and can vary widely from batch-to-batch in purity, proliferation rates, and the development of senescence. In contrast, the M2-10B4 bone marrow stromal cell line (ATCC # CRL-1972), which is also permissive for MCMV, has been reported to produce high-titer stocks of MCMV and has the considerable advantages of growing rapidly and consistently. However, detailed methods using these cells have not been published. Methods We modified existing protocols to use M2-10B4 cells for measuring MCMV titers by plaque assay. Results We found that MCMV plaques could be easily resolved on monolayers of M2-10B4 cells. Moreover, plaques formed normally even when cultures of M2-10B4 cells were less than 50% confluent on the day of infection, as long as we also used a reduced viscosity overlay. Conclusions Overall, our protocol enabled us to use a consistent cell line to assess viral titers, rather than repeatedly producing primary MEFs. It also allowed us to start the assay with 4-fold fewer cells than would be required to generate a confluent monolayer, reducing the lead-time prior to the start of the assay. Finally, the reduced viscosity CMC could be handled by pipet and did not need to be pre-mixed with media, thus increasing its shelf-life and ease-of-use. We describe our results here, along with detailed protocols for the use of the M2-10B4 cell lines to determine the titer and grow stocks of MCMV. PMID:24742045

  10. Glutamate receptors

    DEFF Research Database (Denmark)

    Kristensen, Anders S; Geballe, Matthew T; Snyder, James P

    2006-01-01

    Fast excitatory synaptic transmission in the CNS relies almost entirely on the neurotransmitter glutamate and its family of ion channel receptors. An appreciation of the coupling between agonist binding and channel opening has advanced rapidly during the past five years, largely as a result of ne...

  11. Monitoring tissue inflammation and responses to drug treatments in early stages of mice bone fracture using 50 MHz ultrasound.

    Science.gov (United States)

    Chen, Yen-Chu; Lin, Yi-Hsun; Wang, Shyh-Hau; Lin, Shih-Ping; Shung, K Kirk; Wu, Chia-Ching

    2014-01-01

    Bone fracture induces moderate inflammatory responses that are regulated by cyclooxygenase-2 (COX-2) or 5-lipoxygenase (5-LO) for initiating tissue repair and bone formation. Only a handful of non-invasive techniques focus on monitoring acute inflammation of injured bone currently exists. In the current study, we monitored in vivo inflammation levels during the initial 2 weeks of the inflammatory stage after mouse bone fracture utilizing 50 MHz ultrasound. The acquired ultrasonic images were correlated well with histological examinations. After the bone fracture in the tibia, dynamic changes in the soft tissue at the medial-posterior compartment near the fracture site were monitored by ultrasound on the days of 0, 2, 4, 7, and 14. The corresponding echogenicity increased on the 2nd, 4th, and 7th day, and subsequently declined to basal levels after the 14th day. An increase of cell death was identified by the positive staining of deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) assay and was consistent with ultrasound measurements. The increases of both COX-2 and Leukotriene B4 receptor 1 (BLT1, 5-LO-relative receptor), which are regulators for tissue inflammation, in the immunohistochemistry staining revealed their involvement in bone fracture injury. Monitoring the inflammatory response to various non-steroidal anti-inflammatory drugs (NSAIDs) treatments was investigated by treating injured mice with a daily oral intake of aspirin (Asp), indomethacin (IND), and a selective COX-2 inhibitor (SC-236). The Asp treatment significantly reduced fracture-increased echogenicity (hyperechogenicity, pultrasound images as well as inhibited cell death, and expression of COX-2 and BLT1. In contrast, treatment with IND or SC-236 did not reduce the hyperechogenicity, as confirmed by cell death (TUNEL) and expression levels of COX-2 or BLT1. Taken together, the current study reports the feasibility of a non-invasive ultrasound method capable of monitoring post

  12. MiR-193b, downregulated in Ewing Sarcoma, targets the ErbB4 oncogene to inhibit anchorage-independent growth.

    Directory of Open Access Journals (Sweden)

    Colin Moore

    Full Text Available Ewing Sarcoma is an aggressive, oncofusion-driven, malignant neoplasm of bone and soft tissue affecting predominantly children and young adults. Seeking to identify potential novel therapeutic targets/agents for this disease, our previous studies uncovered microRNAs regulated by EWS/Fli1, the most common oncofusion, with growth modulatory properties. In the present study, we sought to identify EWS/Fli1-repressed, growth suppressive, microRNAs potentially amenable to replacement in Ewing Sarcoma cells. Eight microRNAs (143, 153, 184, 193b, 195, 203, 206 and 223 were selected for evaluation as EWS/Fli1-repressed and underexpressed in Ewing Sarcoma cells, and reported to be growth suppressive in other pediatric or/and adult cancers. The selected miRs, and appropriate non-targeting controls, were introduced into two different Ewing Sarcoma cell lines (A673 and SK-ES-1, and effects on growth were examined using a high and low-density growth assay. MiR-193b was growth inhibitory in both assays and cell lines. In subsequent analyses, we found that stable overexpression of miR-193b also inhibits anchorage-independent growth in both A673 and SK-ES-1 cells. We further show that miR-193b negatively regulates expression of the ErbB4 oncogene in A673 and SK-ES-1 cells, and that depletion of ErbB4 is itself inhibitory to anchorage-independent growth in the same cell lines. Together, our studies show that the EWS/Fli1-repressed miR-193b is growth suppressive in Ewing Sarcoma, and identify ErbB4 as a target gene and candidate mediator of this growth suppression.

  13. Attenuated bioluminescent Brucella melitensis mutants GR019 (virB4), GR024 (galE), and GR026 (BMEI1090-BMEI1091) confer protection in mice.

    Science.gov (United States)

    Rajashekara, Gireesh; Glover, David A; Banai, Menachem; O'Callaghan, David; Splitter, Gary A

    2006-05-01

    In vivo bioluminescence imaging is a persuasive approach to investigate a number of issues in microbial pathogenesis. Previously, we have applied bioluminescence imaging to gain greater insight into Brucella melitensis pathogenesis. Endowing Brucella with bioluminescence allowed direct visualization of bacterial dissemination, pattern of tissue localization, and the contribution of Brucella genes to virulence. In this report, we describe the pathogenicity of three attenuated bioluminescent B. melitensis mutants, GR019 (virB4), GR024 (galE), and GR026 (BMEI1090-BMEI1091), and the dynamics of bioluminescent virulent bacterial infection following vaccination with these mutants. The virB4, galE, and BMEI1090-BMEI1091 mutants were attenuated in interferon regulatory factor 1-deficient (IRF-1(-/-)) mice; however, only the GR019 (virB4) mutant was attenuated in cultured macrophages. Therefore, in vivo imaging provides a comprehensive approach to identify virulence genes that are relevant to in vivo pathogenesis. Our results provide greater insights into the role of galE in virulence and also suggest that BMEI1090 and downstream genes constitute a novel set of genes involved in Brucella virulence. Survival of the vaccine strain in the host for a critical period is important for effective Brucella vaccines. The galE mutant induced no changes in liver and spleen but localized chronically in the tail and protected IRF-1(-/-) and wild-type mice from virulent challenge, implying that this mutant may serve as a potential vaccine candidate in future studies and that the direct visualization of Brucella may provide insight into selection of improved vaccine candidates.

  14. MICROWAVE SYNTHESIS OF B4C–Al2O3 COMPOSITE IN A MECHANICALLY ACTIVATED Al/B2O3/C POWDER MIXTURE

    Directory of Open Access Journals (Sweden)

    Elyar Shaker

    2015-12-01

    Full Text Available B4C–Al2O3 composite powder was produced by aluminothermic reduction in Al/B2O3/C system. In this research, microwave heating technique was used to synthesize desired composite. The ball milling of powder mixtures was performed in order to study the effect of mechanical activation on the synthesis process. The synthesis mechanism in this system was investigated by examining the corresponding binary sub-reactions. The self-sustaining reduction of boron oxide by Al was recognized to be the triggering step in overall reaction.

  15. Immobilization of Rhodococcus erythropolis B4 on radiation crosslinked poly(vinylpyrrolidone) hydrogel: Application to the degradation of polycyclic aromatic hydrocarbons

    Energy Technology Data Exchange (ETDEWEB)

    Djefal-Kerrar, A. [Division of Nuclear Applications, Nuclear Research Centre of Algiers, 2 Bd Frantz Fanon BP-399 Alger-gare, Algiers (Algeria)], E-mail: kerasdjef@yahoo.fr; Gais, S.; Ouallouche, K.; Nacer Khodja, A.; Mahlous, M. [Division of Nuclear Applications, Nuclear Research Centre of Algiers, 2 Bd Frantz Fanon BP-399 Alger-gare, Algiers (Algeria); Hacene, H. [Biological Sciences Institute, Science and Technology University Houari Boumediene, Algiers (Algeria)

    2007-12-15

    A poly(vinylpyrrolidone) (PVP) hydrogel crosslinked by gamma radiation was used to immobilize, by adsorption, Rhodococcus erythropolis B4 strain. Immobilized cells were tested for their capacity to degrade naphthalene and anthracene, under aerobic conditions. The results showed that, the strain fixed is capable of growing in the presence of naphthalene or anthracene as a unique source of carbon. It was also shown that, the fixed strain can be preserved by freeze-drying for further use. The biodegradation capacity was improved during the second use.

  16. Stratification by Smoking Status Reveals an Association of CHRNA5-A3-B4 Genotype with Body Mass Index in Never Smokers

    OpenAIRE

    Taylor, Amy E.; Morris, Richard W.; Fluharty, Meg E.; Bjorngaard, Johan H.; Åsvold, Bjørn Olav; Gabrielsen, Maiken E.; Campbell, Archie; Marioni, Riccardo; Kumari, Meena; Hällfors, Jenni; Männistö, Satu; Marques-Vidal, Pedro; Kaakinen, Marika; Cavadino, Alana; Postmus, Iris

    2014-01-01

    We previously used a single nucleotide polymorphism (SNP) in the CHRNA5-A3-B4 gene cluster associated with heaviness of smoking within smokers to confirm the causal effect of smoking in reducing body mass index (BMI) in a Mendelian randomisation analysis. While seeking to extend these findings in a larger sample we found that this SNP is associated with 0.74% lower body mass index (BMI) per minor allele in current smokers (95% CI -0.97 to -0.51, P = 2.00 × 10(-10)), but also unexpectedly foun...

  17. Enterococcus faecalis PrgJ, a VirB4-Like ATPase, Mediates pCF10 Conjugative Transfer through Substrate Binding

    OpenAIRE

    Li, Feng; Alvarez-Martinez, Cristina; Chen, Yuqing; Choi, Kyoung-Jae; Yeo, Hye-Jeong; Christie, Peter J.

    2012-01-01

    The Enterococcus faecalis prg and pcf genes of plasmid pCF10 encode a type IV secretion system (T4SS) required for conjugative transfer. PrgJ is a member of the VirB4 family of ATPases that are universally associated with T4SSs. Here, we report that purified PrgJ dimers displayed ATP binding and hydrolysis activities. A PrgJ nucleoside triphosphate (NTP) binding site mutation (K471E) slightly diminished ATP binding but abolished ATP hydrolysis in vitro and blocked pCF10 transfer in vivo. As s...

  18. Immobilization of Rhodococcus erythropolis B4 on radiation crosslinked poly(vinylpyrrolidone) hydrogel: Application to the degradation of polycyclic aromatic hydrocarbons

    Science.gov (United States)

    Djefal-Kerrar, A.; Gais, S.; Ouallouche, K.; Nacer Khodja, A.; Mahlous, M.; Hacène, H.

    2007-12-01

    A poly(vinylpyrrolidone) (PVP) hydrogel crosslinked by gamma radiation was used to immobilize, by adsorption, Rhodococcus erythropolis B4 strain. Immobilized cells were tested for their capacity to degrade naphthalene and anthracene, under aerobic conditions. The results showed that, the strain fixed is capable of growing in the presence of naphthalene or anthracene as a unique source of carbon. It was also shown that, the fixed strain can be preserved by freeze-drying for further use. The biodegradation capacity was improved during the second use.

  19. Immobilization of Rhodococcus erythropolis B4 on radiation crosslinked poly(vinylpyrrolidone) hydrogel: Application to the degradation of polycyclic aromatic hydrocarbons

    International Nuclear Information System (INIS)

    Djefal-Kerrar, A.; Gais, S.; Ouallouche, K.; Nacer Khodja, A.; Mahlous, M.; Hacene, H.

    2007-01-01

    A poly(vinylpyrrolidone) (PVP) hydrogel crosslinked by gamma radiation was used to immobilize, by adsorption, Rhodococcus erythropolis B4 strain. Immobilized cells were tested for their capacity to degrade naphthalene and anthracene, under aerobic conditions. The results showed that, the strain fixed is capable of growing in the presence of naphthalene or anthracene as a unique source of carbon. It was also shown that, the fixed strain can be preserved by freeze-drying for further use. The biodegradation capacity was improved during the second use

  20. Effect of Cutting Parameters on Thrust Force and Surface Roughness in Drilling of Al-2219/B4C/Gr Metal Matrix Composites

    Science.gov (United States)

    Ravindranath, V. M.; Basavarajappa, G. S. Shiva Shankar S.; Suresh, R.

    2016-09-01

    In aluminium matrix composites, reinforcement of hard ceramic particle present inside the matrix which causes tool wear, high cutting forces and poor surface finish during machining. This paper focuses on effect of cutting parameters on thrust force, surface roughness and burr height during drilling of MMCs. In the present work, discuss the influence of spindle speed and feed rate on drilling the pure base alloy (Al-2219), mono composite (Al- 2219+8% B4C) and hybrid composite (Al-2219+8%B4C+3%Gr). The composites were fabricated using liquid metallurgy route. The drilling experiments were conducted by CNC machine with TiN coated HSS tool, M42 (Cobalt grade) and carbide tools at various spindle speeds and feed rates. The thrust force, surface roughness and burr height of the drilled hole were investigated in mono composite and hybrid composite containing graphite particles, the experimental results show that the feed rate has more influence on thrust force and surface roughness. Lesser thrust force and discontinuous chips were produced during machining of hybrid composites when compared with mono and base alloy during drilling process. It is due to solid lubricant property of graphite which reduces the lesser thrust force, burr height and lower surface roughness. When machining with Carbide tool at low feed and high speeds good surface finish was obtained compared to other two types of cutting tool materials.

  1. Advanced first-principles theory of superconductivity including both lattice vibrations and spin fluctuations: The case of FeB4

    Science.gov (United States)

    Bekaert, J.; Aperis, A.; Partoens, B.; Oppeneer, P. M.; Milošević, M. V.

    2018-01-01

    We present an advanced method to study spin fluctuations in superconductors quantitatively and entirely from first principles. This method can be generally applied to materials where electron-phonon coupling and spin fluctuations coexist. We employ it here to examine the recently synthesized superconductor iron tetraboride (FeB4) with experimental Tc˜2.4 K [H. Gou et al., Phys. Rev. Lett. 111, 157002 (2013), 10.1103/PhysRevLett.111.157002]. We prove that FeB4 is particularly prone to ferromagnetic spin fluctuations due to the presence of iron, resulting in a large Stoner interaction strength, I =1.5 eV, as calculated from first principles. The other important factor is its Fermi surface that consists of three separate sheets, among which two are nested ellipsoids. The resulting susceptibility has a ferromagnetic peak around q =0 , from which we calculated the repulsive interaction between Cooper pair electrons using the random phase approximation. Subsequently, we combined the electron-phonon interaction calculated from first principles with the spin fluctuation interaction in fully anisotropic Eliashberg theory calculations. We show that the resulting superconducting gap spectrum is conventional, yet very strongly depleted due to coupling to the spin fluctuations. The critical temperature decreases from Tc=41 K, if they are not taken into account, to Tc=1.7 K, in good agreement with the experimental value.

  2. Sliding-wear resistance of pure near fully-dense B4C under lubrication with water, diesel fuel, and paraffin oil

    DEFF Research Database (Denmark)

    Ortiz, Angel L.; Leal, Victor Manuel Candelario; Borrero-López, Oscar

    2017-01-01

    The sliding-wear resistance of pure near fully-dense B4C is investigated, and the wear mode/mechanisms identified, under lubrication with water, diesel fuel, and paraffin oil. It is found that the wear is mild in the three cases, with specific wear rates (SWRs) of 10−16–10−17 m3/N m. Nonetheless......, the wear resistance of the B4C ceramic is one order of magnitude greater under oil lubrication (1016 N m/m3) than under water lubrication (1015 N m/m3), and twice as great for the specific case of paraffin oil than diesel fuel, attributable to the lubricant’s viscosity. It is also found that the wear mode...... is always abrasion, and that the wear mechanisms are plastic deformation and localized fracture with grain pullout. However, in agreement with the macro-wear data, the severity of the wear damage is lower under lubrication with paraffin oil, followed by diesel fuel, and lastly water. Finally...

  3. Narrow groove and restricted anchors of MHC class I molecule BF2*0401 plus peptide transporter restriction can explain disease susceptibility of B4 chickens.

    Science.gov (United States)

    Zhang, Jianhua; Chen, Yong; Qi, Jianxun; Gao, Feng; Liu, Yanjie; Liu, Jun; Zhou, Xuyu; Kaufman, Jim; Xia, Chun; Gao, George F

    2012-11-01

    The MHC has genetic associations with many diseases, often due to differences in presentation of antigenic peptides by polymorphic MHC molecules to T lymphocytes of the immune system. In chickens, only a single classical class I molecule in each MHC haplotype is expressed well due to coevolution with the polymorphic TAPs which means that resistance and susceptibility to infectious pathogens are particularly easy to observe. Previously, structures of chicken MHC class I molecule BF2*2101 from B21 haplotype showed an unusually large peptide-binding groove that accommodates a broad spectrum of peptides to present as epitopes to CTLs, explaining the MHC-determined resistance of B21 chickens to Marek's disease. In this study, we report the crystal structure of BF2*0401 from the B4 (also known as B13) haplotype, showing a highly positively charged surface hitherto unobserved in other MHC molecules, as well as a remarkably narrow groove due to the allele-specific residues with bulky side chains. Together, these properties limit the number of epitope peptides that can bind this class I molecule. However, peptide-binding assays show that in vitro, BF2*0401 can bind a wider variety of peptides than are found on the surface of B4 cells. Thus, a combination of the specificities of the polymorphic TAP and the MHC results in a very limited set of BF2*0401 peptides with negatively charged anchors to be presented to T lymphocytes.

  4. Coxsackievirus B4 as a Causative Agent of Diabetes Mellitus Type 1: Is There a Role of Inefficiently Treated Drinking Water and Sewage in Virus Spreading?

    Science.gov (United States)

    El-Senousy, Waled M; Abdel-Moneim, Adel; Abdel-Latif, Mahmoud; El-Hefnawy, Mohamed H; Khalil, Rehab G

    2018-03-01

    for isolation of separate EV isolates from treated and untreated water and sewage samples. Characterization of the EV amplicons by RT-PCR followed by sequencing of these isolates revealed high homology (97%) with human coxsackievirus B4 (CV B4) in 60% of the isolates, while the rest of the isolates belonged to poliovirus type 1 and type 2 vaccine strains. On the other hand, characterization of the EV amplicons by RT-PCR followed by sequencing for T1D-EV + children specimens indicated that all samples contained CV B4 with the same sequence characterized in the environmental samples. CV B4-contaminated drinking water or treated sewage may play a role as a causative agent of T1D in children.

  5. Electrical Discharge Machining of Al (6351-5% SiC-10% B4C Hybrid Composite: A Grey Relational Approach

    Directory of Open Access Journals (Sweden)

    S. Suresh Kumar

    2014-01-01

    Full Text Available The goal of the present experimental work is to optimize the electrical discharge machining (EDM parameters of aluminum alloy (Al 6351 matrix reinforced with 5 wt.% silicon carbide (SiC and 10 wt.% boron carbide (B4C particles fabricated through the stir casting route. Multiresponse optimization was carried out through grey relational analysis (GRA with an objective to minimize the machining characteristics, namely electrode wear ratio (EWR, surface roughness (SR and power consumption (PC. The optimal combination of input parameters is identified, which shows the significant enhancement in process characteristics. Contributions of each machining parameter to the responses are calculated using analysis of variance (ANOVA. The result shows that the pulse current contributes more (83.94% to affecting the combined output responses.

  6. Utilizing alkoxyphenyl substituents for side-chain engineering of efficient benzo[1,2-b:4,5-b ']dithiophene-based small molecule organic solar cells

    DEFF Research Database (Denmark)

    Du, Zhengkun; Chen, Weichao; Qiu, Meng

    2015-01-01

    A new two-dimensional (2D) conjugated small molecule, namely DCA3TBDTP, with an alkoxyphenyl substituted benzo[1,2-b: 4,5-b']dithiophene (BDT) unit as the central core, octyl cyanoacetate as the end-capped groups and terthiophene as the pi-linked bridge, was designed and synthesized for solution-processed......-gap (1.82 eV) and a high decomposition temperature (362 degrees C). By applying the simple solution spin-coating fabrication process, the bulk heterojunction (BHJ) OSCs based on DCA3TBDTP and [6,6]-phenyl-C-61-butyric acid methyl ester (PC61BM) exhibited a good power conversion efficiency (PCE) of 4...

  7. Using remote-sensing and the Simple Biosphere model (SiB4) to analyze the seasonality and productivity of the terrestrial biosphere.

    Science.gov (United States)

    Cheeseman, M.; Denning, S.; Baker, I. T.

    2017-12-01

    Understanding the variability and seasonality of carbon fluxes from the terrestrial biosphere is integral to understanding the mechanisms and drivers of the global carbon cycle. However, there are many regions across the globe where in situ observations are sparse, such as the Amazon rainforest and the African Sahel. The latest version of the Simple-Biosphere model (SiB4) predicts a suite of biophysical variables such as terrestrial carbon flux (GPP), solar induced fluorescence (SIF), fraction of photosynthetically active radiation (FPAR), and leaf area index (LAI). By comparing modeled values to a suite of satellite and in situ observations we produce a robust analysis of the seasonality and productivity of the terrestrial biosphere in a variety of biome types across the globe.

  8. Discovery of novel anti-angiogenesis agents. Part 7: Multitarget inhibitors of VEGFR-2, TIE-2 and EphB4.

    Science.gov (United States)

    Li, Chuansheng; Shan, Yuanyuan; Sun, Ying; Si, Ru; Liang, Liyuan; Pan, Xiaoyan; Wang, Binghe; Zhang, Jie

    2017-12-01

    Herein, we embarked on a structural optimization campaign aiming at the discovery of second generation anti-angiogenesis agents with our previously reported BPS-7 as lead compound. A library of 27 compounds has been afforded based on the highly conserved ATP-binding pocket of VEGFR-2, Tie-2, and EphB4. Several title compounds exhibited simultaneous inhibitory effects against three angiogenic RTKs. These compounds with a 'triplet' inhibition profile have been identified as novel anti-angiogenic and anticancer agents. The representative VDAU11 displayed prominent anti-angiogenic and anticancer potency and could be considered as a candidate for further optimization. These results indicate that N-(pyridin-2-yl)acrylamide could serve as a novel hinge-binding group of triple inhibitors. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  9. Thermoluminescence studies of manganese doped calcium tetraborate (CaB4O7:Mn) nanocrystal synthesized by co-precipitation method

    Science.gov (United States)

    Erfani Haghiri, Maryam; Saion, Elias; wan Abdullah, Wan Saffiey; Soltani, Nayereh; Hashim, Mansor; Navasery, Manizheh; Shafaei, Mohammad Ali

    2013-09-01

    Manganese (Mn) doped bone-equivalent calcium tetraborate (CaB4O7) nanocrystals were synthesized using co-precipitation and thermal treatment techniques. The synthesized nanophosphors are found to possess the monoclinic structure and have the particle size about 9 nm. They showed good luminescence quantum efficiency and enough potential for radiation dose measurement in medical and industrial purposes. The variation of dopant concentrations was investigated from 0.1 to 2 mol% and it was found that the optimal concentration of 1.4 mol% Mn has the highest sensitivity among other concentrations. The results revealed that Mn enhance the thermoluminescence (TL) sensitivity about 80 times higher than the un-doped samples at 1 kGy and the TL response over a wide range of doses from 0.05 Gy to 2.0 kGy increased linearly with increasing the absorbed dose.

  10. Localization of MOs and electronic populations in closo-carboranes 1, 5-C2B3H5 and 1,6-C2B4H6

    International Nuclear Information System (INIS)

    Semenov, S.G.

    1988-01-01

    We have analyzed the electronic populations of chemical bonds and atoms in the highly symmetric closo-carboranes 1,5-C 2 B 3 H 5 (I) and 1,6-C 2 B 4 H 6 (II). The overlap populations σ/sub XY/ are compared with the corresponding Mulliken indices. We note substantial nonadditivity of the populations σ/sub XY/ for closed three-center bonds BCB' and the closeness of the total overlap populations σ/sub t/ to its maximum value. We have established the localization of the natural MOs on the bonds CH, BH, and BCB', and for molecule I also on the CBC' bonds. The effects of conjugation of bonds in the closo-carborane polyhedron are apparent in the linear dependence of these MOs. The corresponding nonorthogonal hybrid AOs of carbon and boron are also linearly dependent. We have formulated the concept of unshared population of an atom

  11. Serum Bactericidal Antibody Responses of Adults Immunized with the MenB-4C Vaccine against Genetically Diverse Serogroup B Meningococci

    Science.gov (United States)

    Giuntini, Serena; Lujan, Eduardo; Gibani, Malick M.; Dold, Christina; Rollier, Christine S.; Pollard, Andrew J.

    2016-01-01

    ABSTRACT MenB-4C is a meningococcal vaccine for the prevention of serogroup B disease. The vaccine contains factor H binding protein (FHbp) and three other antigens that can elicit serum bactericidal antibodies (SBA). For vaccine licensure, efficacy was inferred from the SBA responses against three antigen-specific indicator strains. The relation between those results and broad protection against circulating genetically diverse strains is not known. Twenty adults were immunized with two doses of MenB-4C given 1 to 2 months apart. SBA activity against 3 reference strains and 15 serogroup B test strains (6 from college outbreaks) was measured. Compared to the preimmunization titers, 70%, 95%, and 95% of subjects had ≥4-fold increases in the titers of anti-PorA P1.4, anti-NadA, and anti-FHbp antibodies against the reference strains, respectively. In contrast, only 25 to 45% of the subjects had ≥4-fold increases in responses to 10 of the 15 test strains, including 8 that expressed one to three of the antigens in the vaccine. At 1 month, the majority of subjects with <4-fold titer increases had serum titers of ≥1:4, which are considered sufficient for protection. However, the titers against four strains declined to <1:4 by 4 to 6 months in one-third to greater than 50% of the subjects tested. Clinically relevant isolates are often more resistant to SBA than the indicator strains used to measure antigen-specific SBA. A working model is that the percentage of subjects with titers of ≥1:4 at 1 month postimmunization correlates with short-term protection against that strain, whereas the percentage of subjects with ≥4-fold titer increases represents a more robust response. (The protocol used at the Oxford Vaccine Group has been registered at ClinicalTrials.gov under registration no. NCT02398396.) PMID:27847367

  12. Formalin-inactivated EV71 vaccine candidate induced cross-neutralizing antibody against subgenotypes B1, B4, B5 and C4A in adult volunteers.

    Directory of Open Access Journals (Sweden)

    Ai-Hsiang Chou

    Full Text Available Enterovirus 71 (EV71 has caused several epidemics of hand, foot and mouth diseases (HFMD in Asia. No effective EV71 vaccine is available. A randomized and open-label phase I clinical study registered with ClinicalTrials.gov #NCT01268787, aims to evaluate the safety, reactogenicity and immunogenicity of a formalin-inactivated EV71 vaccine candidate (EV71vac at 5- and 10-µg doses. In this study we report the cross-neutralizing antibody responses from each volunteer against different subgenotypes of EV71 and CVA16.Sixty eligible healthy adults were recruited and vaccinated. Blood samples were obtained on day 0, 21 and 42 and tested against B1, B4, B5, C2, C4A, C4B and CVA16 for cross-neutralizing antibody responses.The immunogenicity of both 5- and 10- µg doses were found to be very similar. Approximately 45% of the participants had 4-fold increase in Nt, but there was no further increase in Nt after the second dose. EV71vac induced very strong cross-neutralizing antibody responses in >85% of volunteers without pre-existing Nt against subgenotype B1, B5 and C4A. EV71vac elicited weak cross-neutralizing antibody responses (∼20% of participants against a C4B and Coxsackie virus A16. Over 90% of vaccinated volunteers did not develop cross-neutralizing antibody responses (Nt<8 against a C2 strain. EV71vac can boost and significantly enhance the neutralizing antibody responses in volunteers who already had pre-vaccination antibodies against EV71 and/or CVA16.EV71vac is efficient in eliciting cross-neutralizing antibody responses against EV71 subgenotypes B1, B4, B5, and C4A, and provides the rationale for its evaluation in phase II clinical trials.ClinicalTrials.gov NCT01268787.

  13. A vacuolar sorting receptor-independent sorting mechanism for storage vacuoles in soybean seeds.

    Science.gov (United States)

    Maruyama, Nobuyuki; Matsuoka, Yuki; Yokoyama, Kazunori; Takagi, Kyoko; Yamada, Tetsuya; Hasegawa, Hisakazu; Terakawa, Teruhiko; Ishimoto, Masao

    2018-01-18

    The seed storage proteins of soybean (Glycine max) are composed mainly of glycinin (11S globulin) and β-conglycinin (7S globulin). The subunits of glycinin (A1aB1b, A1bB2, A2B1a, A3B4, and A5A4B3) are synthesized as a single polypeptide precursor. These precursors are assembled into trimers with a random combination of subunits in the endoplasmic reticulum, and are sorted to the protein storage vacuoles. Proteins destined for transport to protein storage vacuoles possess a vacuolar sorting determinant, and in this regard, the A1aB1b subunit contains a C-terminal peptide that is sufficient for its sorting to protein storage vacuoles. The A3B4 subunit, however, lacks a corresponding C-terminal sorting determinant. In this study, we found that, unlike the A1aB1b subunit, the A3B4 subunit does not bind to previously reported vacuolar sorting receptors. Despite this difference, we observed that the A3B4 subunit is sorted to protein storage vacuoles in a transgenic soybean line expressing the A3B4 subunit of glycinin. These results indicate that a protein storage vacuolar sorting mechanism that functions independently of the known vacuolar sorting receptors in seeds might be present in soybean seeds.

  14. The Murine CAR Homolog Is a Receptor for Coxsackie B Viruses and Adenoviruses

    Science.gov (United States)

    Bergelson, Jeffrey M.; Krithivas, Anita; Celi, Leo; Droguett, Gustavo; Horwitz, Marshall S.; Wickham, Thomas; Crowell, Richard L.; Finberg, Robert W.

    1998-01-01

    Complementary DNA clones encoding the murine homolog (mCAR) of the human coxsackievirus and adenovirus receptor (CAR) were isolated. Nonpermissive CHO cells transfected with mCAR cDNA became susceptible to infection by coxsackieviruses B3 and B4 and showed increased susceptibility to adenovirus-mediated gene transfer. These results indicate that the same receptor is responsible for virus interactions with both murine and human cells. Analysis of receptor expression in human and murine tissues should be useful in defining factors governing virus tropism in vivo. PMID:9420240

  15. Detección del antígeno Tn en tumores epiteliales con la lectina de Vicia villosa isolectina B4.

    Directory of Open Access Journals (Sweden)

    Catalina Limpias

    2010-10-01

    Full Text Available Antecedentes. Los epítopes T, Tn y sTn, se expresan en un alto porcentaje de tumores epiteliales y pueden detectarse con anticuerpos monoclonales y lectinas. Objetivo. Evaluar diferencias de expresión del antígeno Tn en cortes histológicos de epitelios no neoplásicos y tumores epiteliales mediante isolectina B4 de Vicia villosa. Material y métodos. Se evaluaron semicuantitativamente localización, intensidad y porcentaje de expresión del antígeno en carcinomas in-situ e infiltrantes y epitelios no neoplásicos de cérvix, seno y urotelio, mediante isolectina B4. Resultados La expresión de Tn en cérvix predominó en membrana de células no neoplásicas y citoplasma de células tumorales; su intensidad fue mayor en carcinomas in-situ e infiltrantes comparado con epitelio no neoplásico aunque en este el porcentaje de expresión fue mayor. En seno, la expresión de Tn fue predominantemente citoplasmática con intensidad similar, el porcentaje de expresión fué mayor en carcinomas ductales in-situ e infiltrantes. En urotelio no neoplásico y tumoral la expresión de Tn predominó en citoplasma; la intensidad y el porcentaje de expresión fueron mayores en neoplasias no invasivas de bajo y alto grado, mientras que en urotelio no neoplásico fue baja y no hubo tendencia definida en tumores infiltrantes. Conclusiones. La detección del antígeno Tn mediante la lectina VVB4 mostró una mayor extensión de marcación en carcinomas ductales de seno en relación con el epitelio no neoplásico, pero no mostró una tendencia definida entre el tejido normal, ni diferentes etapas del desarrollo de los tumores de cérvix y urotelio. Estos hallazgos pueden atribuirse a la heterogeneidad de los procesos carcinogénicos o a que la especificidad de la lectina VVB4 no está restringida a este antígeno.

  16. The mechanism of thermal explosion (TE) synthesis of TiC–TiB2 particulate locally reinforced steel matrix composites from an Al–Ti–B4C system via a TE-casting route

    International Nuclear Information System (INIS)

    Zou Binglin; Shen Ping; Cao Xueqiang; Jiang Qichuan

    2012-01-01

    Highlights: ► We successfully fabricated TiC–TiB 2 locally reinforced steel matrix composites. ► We investigated the product microstructure and formation mechanism of TiC and TiB 2 . ► The formation mechanism during casting is dependent on B 4 C particle size. ► Fe melt promotes the full dissociation of remnant B 4 C particles during casting. ► The relationship between the mechanisms in the ERF and during casting was proposed. - Abstract: TiC–TiB 2 particulate locally reinforced steel matrix composites were fabricated by a novel TE-casting route from an Al–Ti–B 4 C system with various B 4 C particle sizes. The formation mechanism of TiC and TiB 2 in the locally reinforced regions was investigated. The results showed that TiC and TiB 2 are formed and precipitated from Al–Ti–B–C melt resulting from the dissociation of B 4 C into Al–Ti melt when the concentrations of B and C atoms in the Al–Ti–B–C melt become saturated. However, in the case of coarse B 4 C powders (≥40 μm) used, the primary reaction in the Al–Ti–B–C melt is quite limited due to the poor dissociation of B 4 C. The poured steel melt infiltrates into the primary reaction product and thus leads to the formation of Al–Fe–Ti–B–C melt, thanks to the favorable reaction of molten Fe with remnant B 4 C, and then TiC and TiB 2 are further formed and precipitated from the saturated Al–Fe–Ti–B–C melt. The relationship between the mechanisms of thermal explosion (TE) synthesis of TiC and TiB 2 in the electric resistance furnace and during casting was proposed.

  17. Identification of endogenous opioid receptor components in rat brain using a monoclonal antibody

    Energy Technology Data Exchange (ETDEWEB)

    Bero, L.A.; Roy, S.; Lee, N.M.

    1988-11-01

    A monoclonal antibody generated against the tertiary structure of a partially purified opioid binding protein was used to probe the structure of the dynorphin and beta-endorphin receptors. The Fab fragment 3B4F11 inhibited completely the binding of 125I-beta-endorphin and (3H)dynorphin to rat brain P2 membranes with IC50 values of 26 ng/ml and 40 ng/ml, respectively. To explore further the interaction of 3B4F11 with the beta-endorphin receptor, the effect of the Fab fragment on 125I-beta-endorphin cross-linking to rat brain membranes was examined. 125I-beta-endorphin was covalently bound to three major species of approximate molecular weights 108,000, 73,000, and 49,000. The delta-selective ligand D-Pen2, D-pen5enkephalin was least effective at inhibiting the cross-linking of beta-endorphin, whereas the micro-selective ligand Tyr-D-Ala-Gly-NMe-Phe-Gly-ol and kappa-selective ligand U50488 inhibited beta-endorphin cross-linking to the 108,000 and 73,000 Da species. Both 3B4F11 and beta-endorphin prevented the covalent binding of 125I-beta-endorphin to all three labeled species. These findings suggest that micro and kappa receptor types might have some structural similarities, whereas the delta receptor type might differ in molecular size. In addition, the micro, kappa, and delta ligands might have different primary sequences, whereas their tertiary structures might share regions of molecular homology with all three receptor constituents labeled by 125I-beta-endorphin. 3B4F11 will be a valuable tool for the purification and isolation of the several components of the beta-endorphin receptor complex.

  18. Benzo[1,2-b:4,5-b′]Dithiophene-6,7-Difluoroquinoxaline Small Molecule Donors with >8% BHJ Solar Cell Efficiency

    KAUST Repository

    Liang, Ru-Ze

    2017-07-14

    Solution-processable small molecule (SM) donors are promising alternatives to their polymer counterparts in bulk-heterojunction (BHJ) solar cells. While SM donors with favorable spectral absorption, self-assembly patterns, optimum thin-film morphologies, and high carrier mobilities in optimized donor–acceptor blends are required to further BHJ device efficiencies, material structure governs each one of those attributes. As a result, the rational design of SM donors with gradually improved BHJ solar cell efficiencies must concurrently address: (i) bandgap tuning and optimization of spectral absorption (inherent to the SM main chain) and (ii) pendant-group substitution promoting structural order and mediating morphological effects. In this paper, the rational pendant-group substitution in benzo[1,2-b:4,5-b′]dithiophene–6,7-difluoroquinoxaline SMs is shown to be an effective approach to narrowing the optical gap (Eopt) of the SM donors (SM1 and SM2), without altering their propensity to order and form favorable thin-film BHJ morphologies with PC71BM. Systematic device examinations show that power conversion efficiencies >8% and open-circuit voltages (VOC) nearing 1 V can be achieved with the narrow-gap SM donor analog (SM2, Eopt = 1.6 eV) and that charge transport in optimized BHJ solar cells proceeds with minimal, nearly trap-free recombination. Detailed device simulations, light intensity dependence, and transient photocurrent analyses emphasize how carrier recombination impacts BHJ device performance upon optimization of active layer thickness and morphology.

  19. Coxsackie B4 virus infection of β cells and natural killer cell insulitis in recent-onset type 1 diabetic patients

    Science.gov (United States)

    Dotta, Francesco; Censini, Stefano; van Halteren, Astrid G. S.; Marselli, Lorella; Masini, Matilde; Dionisi, Sabrina; Mosca, Franco; Boggi, Ugo; Muda, Andrea Onetti; Prato, Stefano Del; Elliott, John F.; Covacci, Antonello; Rappuoli, Rino; Roep, Bart O.; Marchetti, Piero

    2007-01-01

    Type 1 diabetes is characterized by T cell-mediated autoimmune destruction of pancreatic β cells. Several studies have suggested an association between Coxsackie enterovirus seroconversion and onset of disease. However, a direct link between β cell viral infection and islet inflammation has not been established. We analyzed pancreatic tissue from six type 1 diabetic and 26 control organ donors. Immunohistochemical, electron microscopy, whole-genome ex vivo nucleotide sequencing, cell culture, and immunological studies demonstrated Coxsackie B4 enterovirus in specimens from three of the six diabetic patients. Infection was specific of β cells, which showed nondestructive islet inflammation mediated mainly by natural killer cells. Islets from enterovirus-positive samples displayed reduced insulin secretion in response to glucose and other secretagogues. In addition, virus extracted from positive islets was able to infect β cells from human islets of nondiabetic donors, causing viral inclusions and signs of pyknosis. None of the control organ donors showed signs of viral infection. These studies provide direct evidence that enterovirus can infect β cells in patients with type 1 diabetes and that infection is associated with inflammation and functional impairment. PMID:17360338

  20. Coxsackie B4 virus infection of beta cells and natural killer cell insulitis in recent-onset type 1 diabetic patients.

    Science.gov (United States)

    Dotta, Francesco; Censini, Stefano; van Halteren, Astrid G S; Marselli, Lorella; Masini, Matilde; Dionisi, Sabrina; Mosca, Franco; Boggi, Ugo; Muda, Andrea Onetti; Del Prato, Stefano; Elliott, John F; Covacci, Antonello; Rappuoli, Rino; Roep, Bart O; Marchetti, Piero

    2007-03-20

    Type 1 diabetes is characterized by T cell-mediated autoimmune destruction of pancreatic beta cells. Several studies have suggested an association between Coxsackie enterovirus seroconversion and onset of disease. However, a direct link between beta cell viral infection and islet inflammation has not been established. We analyzed pancreatic tissue from six type 1 diabetic and 26 control organ donors. Immunohistochemical, electron microscopy, whole-genome ex vivo nucleotide sequencing, cell culture, and immunological studies demonstrated Coxsackie B4 enterovirus in specimens from three of the six diabetic patients. Infection was specific of beta cells, which showed nondestructive islet inflammation mediated mainly by natural killer cells. Islets from enterovirus-positive samples displayed reduced insulin secretion in response to glucose and other secretagogues. In addition, virus extracted from positive islets was able to infect beta cells from human islets of nondiabetic donors, causing viral inclusions and signs of pyknosis. None of the control organ donors showed signs of viral infection. These studies provide direct evidence that enterovirus can infect beta cells in patients with type 1 diabetes and that infection is associated with inflammation and functional impairment.

  1. Reactivity determination of the Al2O3-B4C burnable poison as a function of its concentration in the IPEN/MB-01 reactor

    International Nuclear Information System (INIS)

    Giada, Marino Reis

    2005-01-01

    Burnable poison rods made of Al 2 O 3 -B 4 C pellets with different concentrations of 10 B have been manufactured for a set of experiments in the IPEN/MB-01 zero-power reactor. The experiments evaluated the reactivity of the burnable poison rods as a function of the 10 B concentration, and the shadowing effect on the control rod reactivity worth as a function of the distance between the burnable position rods and the control rod. The results showed that the burnable poison rods have a non-linear behavior as function of the 10 B concentration, starting to reach an asymptotic value for concentrations higher than 7 g/cm 3 of 10 B. The shadowing effect on the control rods was substantial. When the burnable poison rods were beside the control rod, its reactivity worth decreased as much as 30 %, and when they were 10,5 cm distant, the control rod worth decreased by 7 %. The MCNP results for the burnable poison reactivity effects agreed within experimental errors with the measured values. (author)

  2. Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers.

    Science.gov (United States)

    Taylor, Amy E; Morris, Richard W; Fluharty, Meg E; Bjorngaard, Johan H; Åsvold, Bjørn Olav; Gabrielsen, Maiken E; Campbell, Archie; Marioni, Riccardo; Kumari, Meena; Hällfors, Jenni; Männistö, Satu; Marques-Vidal, Pedro; Kaakinen, Marika; Cavadino, Alana; Postmus, Iris; Husemoen, Lise Lotte N; Skaaby, Tea; Ahluwalia, Tarunveer S; Treur, Jorien L; Willemsen, Gonneke; Dale, Caroline; Wannamethee, S Goya; Lahti, Jari; Palotie, Aarno; Räikkönen, Katri; Kisialiou, Aliaksei; McConnachie, Alex; Padmanabhan, Sandosh; Wong, Andrew; Dalgård, Christine; Paternoster, Lavinia; Ben-Shlomo, Yoav; Tyrrell, Jessica; Horwood, John; Fergusson, David M; Kennedy, Martin A; Frayling, Tim; Nohr, Ellen A; Christiansen, Lene; Ohm Kyvik, Kirsten; Kuh, Diana; Watt, Graham; Eriksson, Johan; Whincup, Peter H; Vink, Jacqueline M; Boomsma, Dorret I; Davey Smith, George; Lawlor, Debbie; Linneberg, Allan; Ford, Ian; Jukema, J Wouter; Power, Christine; Hyppönen, Elina; Jarvelin, Marjo-Riitta; Preisig, Martin; Borodulin, Katja; Kaprio, Jaakko; Kivimaki, Mika; Smith, Blair H; Hayward, Caroline; Romundstad, Pål R; Sørensen, Thorkild I A; Munafò, Marcus R; Sattar, Naveed

    2014-12-01

    We previously used a single nucleotide polymorphism (SNP) in the CHRNA5-A3-B4 gene cluster associated with heaviness of smoking within smokers to confirm the causal effect of smoking in reducing body mass index (BMI) in a Mendelian randomisation analysis. While seeking to extend these findings in a larger sample we found that this SNP is associated with 0.74% lower body mass index (BMI) per minor allele in current smokers (95% CI -0.97 to -0.51, P = 2.00 × 10(-10)), but also unexpectedly found that it was associated with 0.35% higher BMI in never smokers (95% CI +0.18 to +0.52, P = 6.38 × 10(-5)). An interaction test confirmed that these estimates differed from each other (P = 4.95 × 10(-13)). This difference in effects suggests the variant influences BMI both via pathways unrelated to smoking, and via the weight-reducing effects of smoking. It would therefore be essentially undetectable in an unstratified genome-wide association study of BMI, given the opposite association with BMI in never and current smokers. This demonstrates that novel associations may be obscured by hidden population sub-structure. Stratification on well-characterized environmental factors known to impact on health outcomes may therefore reveal novel genetic associations.

  3. The PerR-Regulated P1B-4-Type ATPase (PmtA) Acts as a Ferrous Iron Efflux Pump in Streptococcus pyogenes.

    Science.gov (United States)

    Turner, Andrew G; Ong, Cheryl-Lynn Y; Djoko, Karrera Y; West, Nicholas P; Davies, Mark R; McEwan, Alastair G; Walker, Mark J

    2017-06-01

    Streptococcus pyogenes (group A Streptococcus [GAS]) is an obligate human pathogen responsible for a broad spectrum of human disease. GAS has a requirement for metal homeostasis within the human host and, as such, tightly modulates metal uptake and efflux during infection. Metal acquisition systems are required to combat metal sequestration by the host, while metal efflux systems are essential to protect against metal overload poisoning. Here, we investigated the function of PmtA ( P erR-regulated m etal t ransporter A ), a P 1B-4 -type ATPase efflux pump, in invasive GAS M1T1 strain 5448. We reveal that PmtA functions as a ferrous iron [Fe(II)] efflux system. In the presence of high Fe(II) concentrations, the 5448Δ pmtA deletion mutant exhibited diminished growth and accumulated 5-fold-higher levels of intracellular Fe(II) than did the wild type and the complemented mutant. The 5448Δ pmtA deletion mutant also showed enhanced susceptibility to killing by the Fe-dependent antibiotic streptonigrin as well as increased sensitivity to hydrogen peroxide and superoxide. We suggest that the PerR-mediated control of Fe(II) efflux by PmtA is important for bacterial defense against oxidative stress. PmtA represents an exemplar for an Fe(II) efflux system in a host-adapted Gram-positive bacterial pathogen. Copyright © 2017 American Society for Microbiology.

  4. Benzo[1,2-b:4,5-b’]dithiophene-Pyrido[3,4-b]pyrazine Small-Molecule Donors for Bulk Heterojunction Solar Cells

    KAUST Repository

    Wolf, Jannic Sebastian

    2016-01-22

    We report on the synthesis, material properties and BHJ solar cell characteristics of a set of π-conjugated small-molecule (SM) donors composed of benzo[1,2-b:4,5-b′]dithiophene (BDT) and pyrido[3,4-b]pyrazine (PP) units – examining the perspectives of alkyl-substituted PP acceptor motifs in SM designs. In these systems (SM1-4), both the type of side chains derived from the PP motifs and the presence of ring-substituents on BDT critically impact (i) molecular packing, and (ii) thin-film morphologies and charge transport in BHJ solar cells. With the appropriate side-chain pattern, the ring-substituted analogue SM4 stands out: achieving efficiencies of ca. 6.5% with PC71BM, and fine-scale morphologies comparable to those obtained with some of the best-performing polymer donors in BHJ solar cells. 1H-1H DQ-SQ NMR analyses are used to examine the distinct self-assembly pattern of SM4, expected to factor into the development of the BHJ morphology.

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

    Science.gov (United States)

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

    2002-01-01

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

  6. Origin of (0 0 1) orientation and superlattice structure identification in L10-FePt/B4C multilayer thin films

    Science.gov (United States)

    Zhang, Jun; Xie, Jian; Wang, Yi; Wang, Hanbin; Liu, Xiang; Ye, Cong; Wang, Hao

    2015-12-01

    (0 0 1) textured L10 FePt/B4C multilayer thin films have been prepared on amorphous substrates by magnetron sputtering. High resolution transmission electron microscopy investigation indicates that the Fe and Pt atoms stacked alternately along the c-axis of L10 FePt, confirming the formation of the superlattice structure of L10-ordered FePt. The internal stress calculation and geometrical phase analysis confirm the existence of the in-plane tensile strain in the L10 FePt thin films. The diffusion of the B and C atoms into the FePt layers results in expansion of the FePt unit cells in the interfaces, which induces an in-plane tensile strain in the adjacent deep parts of FePt layer. Such an in-plane tensile strain creates a favorable condition for the FePt films to stabilize the (0 0 1) texture because it relaxes the ordering strain energy of FePt during phase transformation.

  7. Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers.

    Directory of Open Access Journals (Sweden)

    Amy E Taylor

    2014-12-01

    Full Text Available We previously used a single nucleotide polymorphism (SNP in the CHRNA5-A3-B4 gene cluster associated with heaviness of smoking within smokers to confirm the causal effect of smoking in reducing body mass index (BMI in a Mendelian randomisation analysis. While seeking to extend these findings in a larger sample we found that this SNP is associated with 0.74% lower body mass index (BMI per minor allele in current smokers (95% CI -0.97 to -0.51, P = 2.00 × 10(-10, but also unexpectedly found that it was associated with 0.35% higher BMI in never smokers (95% CI +0.18 to +0.52, P = 6.38 × 10(-5. An interaction test confirmed that these estimates differed from each other (P = 4.95 × 10(-13. This difference in effects suggests the variant influences BMI both via pathways unrelated to smoking, and via the weight-reducing effects of smoking. It would therefore be essentially undetectable in an unstratified genome-wide association study of BMI, given the opposite association with BMI in never and current smokers. This demonstrates that novel associations may be obscured by hidden population sub-structure. Stratification on well-characterized environmental factors known to impact on health outcomes may therefore reveal novel genetic associations.

  8. B4GALNT2 (GALGT2) Gene Therapy Reduces Skeletal Muscle Pathology in the FKRP P448L Mouse Model of Limb Girdle Muscular Dystrophy 2I.

    Science.gov (United States)

    Thomas, Paul J; Xu, Rui; Martin, Paul T

    2016-09-01

    Overexpression of B4GALNT2 (previously GALGT2) inhibits the development of muscle pathology in mouse models of Duchenne muscular dystrophy, congenital muscular dystrophy 1A, and limb girdle muscular dystrophy 2D. In these models, muscle GALGT2 overexpression induces the glycosylation of α dystroglycan with the cytotoxic T cell glycan and increases the overexpression of dystrophin and laminin α2 surrogates known to inhibit disease. Here, we show that GALGT2 gene therapy significantly reduces muscle pathology in FKRP P448Lneo(-) mice, a model for limb girdle muscular dystrophy 2I. rAAVrh74.MCK.GALGT2-treated FKRP P448Lneo(-) muscles showed reduced levels of centrally nucleated myofibers, reduced variance, increased size of myofiber diameters, reduced myofiber immunoglobulin G uptake, and reduced muscle wasting at 3 and 6 months after treatment. GALGT2 overexpression in FKRP P448Lneo(-) muscles did not cause substantial glycosylation of α dystroglycan with the cytotoxic T cell glycan or increased expression of dystrophin and laminin α2 surrogates in mature skeletal myofibers, but it increased the number of embryonic myosin-positive regenerating myofibers. These data demonstrate that GALGT2 overexpression can reduce the extent of muscle pathology in FKRP mutant muscles, but that it may do so via a mechanism that differs from its ability to induce surrogate gene expression. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  9. Design and performance of combined infrared canopy and belowground warming in the B4WarmED (Boreal Forest Warming at an Ecotone in Danger) experiment.

    Science.gov (United States)

    Rich, Roy L; Stefanski, Artur; Montgomery, Rebecca A; Hobbie, Sarah E; Kimball, Bruce A; Reich, Peter B

    2015-06-01

    Conducting manipulative climate change experiments in complex vegetation is challenging, given considerable temporal and spatial heterogeneity. One specific challenge involves warming of both plants and soils to depth. We describe the design and performance of an open-air warming experiment called Boreal Forest Warming at an Ecotone in Danger (B4WarmED) that addresses the potential for projected climate warming to alter tree function, species composition, and ecosystem processes at the boreal-temperate ecotone. The experiment includes two forested sites in northern Minnesota, USA, with plots in both open (recently clear-cut) and closed canopy habitats, where seedlings of 11 tree species were planted into native ground vegetation. Treatments include three target levels of plant canopy and soil warming (ambient, +1.7°C, +3.4°C). Warming was achieved by independent feedback control of voltage input to aboveground infrared heaters and belowground buried resistance heating cables in each of 72-7.0 m(2) plots. The treatments emulated patterns of observed diurnal, seasonal, and annual temperatures but with superimposed warming. For the 2009 to 2011 field seasons, we achieved temperature elevations near our targets with growing season overall mean differences (∆Tbelow ) of +1.84°C and +3.66°C at 10 cm soil depth and (∆T(above) ) of +1.82°C and +3.45°C for the plant canopies. We also achieved measured soil warming to at least 1 m depth. Aboveground treatment stability and control were better during nighttime than daytime and in closed vs. open canopy sites in part due to calmer conditions. Heating efficacy in open canopy areas was reduced with increasing canopy complexity and size. Results of this study suggest the warming approach is scalable: it should work well in small-statured vegetation such as grasslands, desert, agricultural crops, and tree saplings (<5 m tall). © 2015 John Wiley & Sons Ltd.

  10. Effect of an antibacterial dental varnish on the levels of prostanoids, leukotriene B4, and interleukin-1 beta in gingival crevicular fluid.

    Science.gov (United States)

    Yucel-Lindberg, T; Twetman, S; Sköld-Larsson, K; Modéer, T

    1999-02-01

    The aim of this study was to investigate the effects of a chlorhexidine/thymol-containing dental varnish on the levels of prostaglandin E2 (PGE2), prostaglandin I2 (PGI2), leukotriene B4 (LTB4), and interleukin-1 beta (IL-1 beta) in gingival crevicular fluid (GCF). The material consisted of 15 adolescents undergoing treatment with fixed orthodontic appliances. Four buccal sites adjacent to bands or brackets and exhibiting a mild chronic gingival inflammation were selected in the upper quadrants of each patient. According to a split-mouth technique, the first and second quadrants were randomly treated with either a varnish (Cervitec) containing 1% chlorhexidine diacetate and thymol (CHX/thymol) or a placebo varnish without active ingredients. The varnishes were applied immediately after the baseline registration, and follow-up examinations were carried out after 3, 8, and 30 days. GCF was sampled with the aid of a paper strip and the volume was determined using a Periotron 8000. The concentrations of PGE2, PGI2, LTB4, and IL-1 beta in GCF were assessed using radioimmunoassay and ELISA techniques. The results unveiled statistically significant reductions of PGE2, PGI2, and LTB4 levels in GCF following the active varnish treatment when compared to baseline values. A slight drop in IL-1 beta levels was registered after both active and placebo varnish applications, but the differences were not significant. The results suggest that treatment with an antibacterial varnish decreases the levels of inflammatory mediators PGE2, PGI2, and LTB4 in gingival crevicular fluid and further support the concept that topical application of a CHX/thymol-containing varnish is beneficial in patients with chronic gingival inflammation.

  11. Production of enniatins A, A1, B, B1, B4, J1 by Fusarium tricinctum in solid corn culture: structural analysis and effects on mitochondrial respiration.

    Science.gov (United States)

    Cuomo, Valentina; Randazzo, Antonio; Meca, Giuseppe; Moretti, Antonio; Cascone, Annunziata; Eriksson, Ove; Novellino, Ettore; Ritieni, Alberto

    2013-10-15

    Enniatins (ENs) are secondary fungal metabolites with hexadepsipeptidic chemical structure and they possess a number of potent biological activities that can contaminate several kind of food and foodstuffs increasing the exposure risk for consumers. ENs are produced by several Fusariun strains including Fusarium subglutinans, Fusarium proliferatum and Fusarium tricinctum. Production of a mixture of ENs was performed by culturing F. tricinctum ITEM 9496 on white corn as substrate. The solid culture components were dried and subsequently extracted with water/methanol (50/50 v/v, 0.5% NaCl), homogenised, filtered, extracted by ethyl acetate and analysed by liquid chromatography with diode array detection (LC-DAD). The crude extract was first separated by low pressure liquid chromatography (LPLC) and then further purified by liquid chromatography (LC), resulting in six compounds with a purity higher than 95% as calculated by (1)H NMR, and with a yield of 30-300mg per compound. The chemical structures of the ENs were determined by liquid chromatography coupled to mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR). The biological activity of the resulting ENs was determined using a mitochondrial respiration test. We discovered that all the ENs studied induced an increase in the mitochondrial respiration resulting in uncoupling of the oxidative phosphorylation. This effect was most likely due to flux of K(+) ions into the mitochondrial matrix. The order of potency of the ENs derivatives was: A1>B1>B>A>B4>J1. These results suggest a correlation between the chemical structures and bioactivity and confirm the severe risks for human associated with consumption of enniatins. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Deletion of Galgt2 (B4Galnt2) reduces muscle growth in response to acute injury and increases muscle inflammation and pathology in dystrophin-deficient mice.

    Science.gov (United States)

    Xu, Rui; Singhal, Neha; Serinagaoglu, Yelda; Chandrasekharan, Kumaran; Joshi, Mandar; Bauer, John A; Janssen, Paulus M L; Martin, Paul T

    2015-10-01

    Transgenic overexpression of Galgt2 (official name B4Galnt2) in skeletal muscle stimulates the glycosylation of α dystroglycan (αDG) and the up-regulation of laminin α2 and dystrophin surrogates known to inhibit muscle pathology in mouse models of congenital muscular dystrophy 1A and Duchenne muscular dystrophy. Skeletal muscle Galgt2 gene expression is also normally increased in the mdx mouse model of Duchenne muscular dystrophy compared with the wild-type mice. To assess whether this increased endogenous Galgt2 expression could affect disease, we quantified muscular dystrophy measures in mdx mice deleted for Galgt2 (Galgt2(-/-)mdx). Galgt2(-/-) mdx mice had increased heart and skeletal muscle pathology and inflammation, and also worsened cardiac function, relative to age-matched mdx mice. Deletion of Galgt2 in wild-type mice also slowed skeletal muscle growth in response to acute muscle injury. In each instance where Galgt2 expression was elevated (developing muscle, regenerating muscle, and dystrophic muscle), Galgt2-dependent glycosylation of αDG was also increased. Overexpression of Galgt2 failed to inhibit skeletal muscle pathology in dystroglycan-deficient muscles, in contrast to previous studies in dystrophin-deficient mdx muscles. This study demonstrates that Galgt2 gene expression and glycosylation of αDG are dynamically regulated in muscle and that endogenous Galgt2 gene expression can ameliorate the extent of muscle pathology, inflammation, and dysfunction in mdx mice. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  13. Kinome analysis of receptor-induced phosphorylation in human natural killer cells.

    Directory of Open Access Journals (Sweden)

    Sebastian König

    Full Text Available BACKGROUND: Natural killer (NK cells contribute to the defense against infected and transformed cells through the engagement of multiple germline-encoded activation receptors. Stimulation of the Fc receptor CD16 alone is sufficient for NK cell activation, whereas other receptors, such as 2B4 (CD244 and DNAM-1 (CD226, act synergistically. After receptor engagement, protein kinases play a major role in signaling networks controlling NK cell effector functions. However, it has not been characterized systematically which of all kinases encoded by the human genome (kinome are involved in NK cell activation. RESULTS: A kinase-selective phosphoproteome approach enabled the determination of 188 kinases expressed in human NK cells. Crosslinking of CD16 as well as 2B4 and DNAM-1 revealed a total of 313 distinct kinase phosphorylation sites on 109 different kinases. Phosphorylation sites on 21 kinases were similarly regulated after engagement of either CD16 or co-engagement of 2B4 and DNAM-1. Among those, increased phosphorylation of FYN, KCC2G (CAMK2, FES, and AAK1, as well as the reduced phosphorylation of MARK2, were reproducibly observed both after engagement of CD16 and co-engagement of 2B4 and DNAM-1. Notably, only one phosphorylation on PAK4 was differentally regulated. CONCLUSIONS: The present study has identified a significant portion of the NK cell kinome and defined novel phosphorylation sites in primary lymphocytes. Regulated phosphorylations observed in the early phase of NK cell activation imply these kinases are involved in NK cell signaling. Taken together, this study suggests a largely shared signaling pathway downstream of distinct activation receptors and constitutes a valuable resource for further elucidating the regulation of NK cell effector responses.

  14. Activation of odorant receptor in colorectal cancer cells leads to inhibition of cell proliferation and apoptosis.

    Directory of Open Access Journals (Sweden)

    Lea Weber

    Full Text Available The analysis and functional characterization of ectopically expressed human olfactory receptors (ORs is becoming increasingly important, as many ORs have been identified in several healthy and cancerous tissues. OR activation has been demonstrated to have influence on cancer cell growth and progression. Here, ORs were identified using RNA-Seq analyses and RT-PCR. We demonstrated the OR protein localization in HCT116 cells using immunocytochemistry (IHC. In order to analyze the physiological role of OR51B4, we deorphanized the receptor by the use of CRE-Luciferase assays, conducted calcium imaging experiments as well as scratch- and proliferation assays. Furthermore, western blot analyses revealed the involvement of different protein kinases in the ligand-dependent signaling pathway. Receptor knockdown via shRNA was used to analyze the involvement of OR51B4. We identified OR51B4, which is highly expressed in the colon cancer cell line HCT116 and in native human colon cancer tissues. We deorphanized the receptor and identified Troenan as an effective ligand. Troenan stimulation of HCT116 cells has anti-proliferative, anti-migratory and pro-apoptotic effects, mediated by changes in the intracellular calcium level upon PLC activation. These effects cause changes in the phosphorylation levels of p38, mTor and Akt kinases. Knockdown of the receptor via shRNA confirmed the involvement of OR51B4. This study emphasizes the importance of ectopically expressed ORs in the therapy for several diseases. The findings provide the basis for alternative treatments of colorectal cancer.

  15. Lipophorin Receptor: The Insect Lipoprotein Receptor

    Indian Academy of Sciences (India)

    IAS Admin

    physiology and develop- mental biology of silkworms, and use of silk in industrial applications. The low-density lipoprotein receptor (LDLR), one of the best characterized cell-surface receptors, mediates cholesterol ho- meostasis and other functions in mammals. The members of the LDLR superfamily are structurally related ...

  16. Lipophorin Receptor: The Insect Lipoprotein Receptor

    Indian Academy of Sciences (India)

    Permanent link: http://www.ias.ac.in/article/fulltext/reso/018/08/0748-0755. Keywords. Low-density lipoprotein receptor; lipophorin; lipophorin receptor; insects. Author Affiliations. G Ravikumar1 N B Vijayaprakash1. Seri-biotech Research Laboratory Central Silk Board Kodathi, Carmelaram Post Bangalore 560 035, India.

  17. Specific combination of compound heterozygous mutations in 17β-hydroxysteroid dehydrogenase type 4 (HSD17B4 defines a new subtype of D-bifunctional protein deficiency

    Directory of Open Access Journals (Sweden)

    McMillan Hugh J

    2012-11-01

    Full Text Available Abstract Background D-bifunctional protein (DBP deficiency is typically apparent within the first month of life with most infants demonstrating hypotonia, psychomotor delay and seizures. Few children survive beyond two years of age. Among patients with prolonged survival all demonstrate severe gross motor delay, absent language development, and severe hearing and visual impairment. DBP contains three catalytically active domains; an N-terminal dehydrogenase, a central hydratase and a C-terminal sterol carrier protein-2-like domain. Three subtypes of the disease are identified based upon the domain affected; DBP type I results from a combined deficiency of dehydrogenase and hydratase activity; DBP type II from isolated hydratase deficiency and DBP type III from isolated dehydrogenase deficiency. Here we report two brothers (16½ and 14 years old with DBP deficiency characterized by normal early childhood followed by sensorineural hearing loss, progressive cerebellar and sensory ataxia and subclinical retinitis pigmentosa. Methods and results Biochemical analysis revealed normal levels of plasma VLCFA, phytanic acid and pristanic acid, and normal bile acids in urine; based on these results no diagnosis was made. Exome analysis was performed using the Agilent SureSelect 50Mb All Exon Kit and the Illumina HiSeq 2000 next-generation-sequencing (NGS platform. Compound heterozygous mutations were identified by exome sequencing and confirmed by Sanger sequencing within the dehydrogenase domain (c.101C>T; p.Ala34Val and hydratase domain (c.1547T>C; p.Ile516Thr of the 17β-hydroxysteroid dehydrogenase type 4 gene (HSD17B4. These mutations have been previously reported in patients with severe-forms of DBP deficiency, however each mutation was reported in combination with another mutation affecting the same domain. Subsequent studies in fibroblasts revealed normal VLCFA levels, normal C26:0 but reduced pristanic acid beta-oxidation activity. Both DBP

  18. Isolation and characterization of BetaM protein encoded by ATP1B4 - a unique member of the Na,K-ATPase {beta}-subunit gene family

    Energy Technology Data Exchange (ETDEWEB)

    Pestov, Nikolay B. [Department of Physiology and Pharmacology, University of Toledo College of Medicine, 3000 Arlington Ave., Toledo, OH 43614 (United States); Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow 117997 (Russian Federation); Zhao, Hao [Department of Physiology and Pharmacology, University of Toledo College of Medicine, 3000 Arlington Ave., Toledo, OH 43614 (United States); Basrur, Venkatesha [Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109 (United States); Modyanov, Nikolai N., E-mail: nikolai.modyanov@utoledo.edu [Department of Physiology and Pharmacology, University of Toledo College of Medicine, 3000 Arlington Ave., Toledo, OH 43614 (United States)

    2011-09-09

    Highlights: {yields} Structural properties of BetaM and Na,K-ATPase {beta}-subunits are sharply different. {yields} BetaM protein is concentrated in nuclear membrane of skeletal myocytes. {yields} BetaM does not associate with a Na,K-ATPase {alpha}-subunit in skeletal muscle. {yields} Polypeptide chain of the native BetaM is highly sensitive to endogenous proteases. {yields} BetaM in neonatal muscle is a product of alternative splice mRNA variant B. -- Abstract: ATP1B4 genes represent a rare instance of the orthologous gene co-option that radically changed functions of encoded BetaM proteins during vertebrate evolution. In lower vertebrates, this protein is a {beta}-subunit of Na,K-ATPase located in the cell membrane. In placental mammals, BetaM completely lost its ancestral role and through acquisition of two extended Glu-rich clusters into the N-terminal domain gained entirely new properties as a muscle-specific protein of the inner nuclear membrane possessing the ability to regulate gene expression. Strict temporal regulation of BetaM expression, which is the highest in late fetal and early postnatal myocytes, indicates that it plays an essential role in perinatal development. Here we report the first structural characterization of the native eutherian BetaM protein. It should be noted that, in contrast to structurally related Na,K-ATPase {beta}-subunits, the polypeptide chain of BetaM is highly sensitive to endogenous proteases that greatly complicated its isolation. Nevertheless, using a complex of protease inhibitors, a sample of authentic BetaM was isolated from pig neonatal skeletal muscle by a combination of ion-exchange and lectin-affinity chromatography followed by SDS-PAGE. Results of the analysis of the BetaM tryptic digest using MALDI-TOF and ESI-MS/MS mass spectrometry have demonstrated that native BetaM in neonatal skeletal muscle is a product of alternative splice mRNA variant B and comprised of 351 amino acid residues. Isolated BetaM protein was

  19. Isolation and characterization of BetaM protein encoded by ATP1B4 - a unique member of the Na,K-ATPase β-subunit gene family

    International Nuclear Information System (INIS)

    Pestov, Nikolay B.; Zhao, Hao; Basrur, Venkatesha; Modyanov, Nikolai N.

    2011-01-01

    Highlights: → Structural properties of BetaM and Na,K-ATPase β-subunits are sharply different. → BetaM protein is concentrated in nuclear membrane of skeletal myocytes. → BetaM does not associate with a Na,K-ATPase α-subunit in skeletal muscle. → Polypeptide chain of the native BetaM is highly sensitive to endogenous proteases. → BetaM in neonatal muscle is a product of alternative splice mRNA variant B. -- Abstract: ATP1B4 genes represent a rare instance of the orthologous gene co-option that radically changed functions of encoded BetaM proteins during vertebrate evolution. In lower vertebrates, this protein is a β-subunit of Na,K-ATPase located in the cell membrane. In placental mammals, BetaM completely lost its ancestral role and through acquisition of two extended Glu-rich clusters into the N-terminal domain gained entirely new properties as a muscle-specific protein of the inner nuclear membrane possessing the ability to regulate gene expression. Strict temporal regulation of BetaM expression, which is the highest in late fetal and early postnatal myocytes, indicates that it plays an essential role in perinatal development. Here we report the first structural characterization of the native eutherian BetaM protein. It should be noted that, in contrast to structurally related Na,K-ATPase β-subunits, the polypeptide chain of BetaM is highly sensitive to endogenous proteases that greatly complicated its isolation. Nevertheless, using a complex of protease inhibitors, a sample of authentic BetaM was isolated from pig neonatal skeletal muscle by a combination of ion-exchange and lectin-affinity chromatography followed by SDS-PAGE. Results of the analysis of the BetaM tryptic digest using MALDI-TOF and ESI-MS/MS mass spectrometry have demonstrated that native BetaM in neonatal skeletal muscle is a product of alternative splice mRNA variant B and comprised of 351 amino acid residues. Isolated BetaM protein was also characterized by SELDI-TOF mass

  20. Acetylcholine receptor antibody

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003576.htm Acetylcholine receptor antibody To use the sharing features on this page, please enable JavaScript. Acetylcholine receptor antibody is a protein found in the blood ...

  1. Ternary rare earth metal boride carbides containing two-dimensional boron carbon network: The crystal and electronic structure of R2B4C (R=Tb, Dy, Ho, Er)

    Science.gov (United States)

    Babizhetskyy, Volodymyr; Zheng, Chong; Mattausch, Hansjürgen; Simon, Arndt

    2007-12-01

    The ternary rare earth boride carbides R2B4C (R=Tb, Dy, Ho, Er) have been synthesized by reacting the elements at temperatures between 1800 and 2000K. The crystal structure of Dy2B4C has been determined from single-crystal X-ray diffraction data. It crystallizes in a new structure type in the orthorhombic space group Immm (a=3.2772(6) Å, b=6.567(2) Å, c=7.542(1) Å, Z=2, R1=0.035 (wR2=0.10) for 224 reflections with Io>2σ(Io)). Boron atoms form infinite chains of fused B6 rings in [100] joined with carbon atoms into planar, two-dimensional networks which alternate with planar sheets of rare earth metal atoms. The electronic structure of Dy2B4C was also analyzed using the tight-binding extended Hückel method.

  2. Androgen receptor abnormalities

    NARCIS (Netherlands)

    A.O. Brinkmann (Albert); G.G.J.M. Kuiper (George); C. Ris-Stalpers (Carolyn); H.C.J. van Rooij (Henri); G. Romalo (G.); G. Trifiro (Gianluca); E. Mulder (Eppo); L. Pinsky (L.); H.U. Schweikert (H.); J. Trapman (Jan)

    1991-01-01

    markdownabstract__Abstract__ The human androgen receptor is a member of the superfamily of steroid hormone receptors. Proper functioning of this protein is a prerequisite for normal male sexual differentiation and development. The cloning of the human androgen receptor cDNA and the elucidation of

  3. Androgen receptor abnormalities

    NARCIS (Netherlands)

    Brinkmann, A. O.; Kuiper, G. G.; Ris-Stalpers, C.; van Rooij, H. C.; Romalo, G.; Trifiro, M.; Mulder, E.; Pinsky, L.; Schweikert, H. U.; Trapman, J.

    1991-01-01

    The human androgen receptor is a member of the superfamily of steroid hormone receptors. Proper functioning of this protein is a prerequisite for normal male sexual differentiation and development. The cloning of the human androgen receptor cDNA and the elucidation of the genomic organization of the

  4. Chloroform-Methanol Residue of Coxiella burnetii Markedly Potentiated the Specific Immunoprotection Elicited by a Recombinant Protein Fragment rOmpB-4 Derived from Outer Membrane Protein B of Rickettsia rickettsii in C3H/HeN Mice.

    Directory of Open Access Journals (Sweden)

    Wenping Gong

    Full Text Available The obligate intracellular bacteria, Rickettsia rickettsii and Coxiella burnetii, are the potential agents of bio-warfare/bio-terrorism. Here C3H/HeN mice were immunized with a recombinant protein fragment rOmp-4 derived from outer membrane protein B, a major protective antigen of R. rickettsii, combined with chloroform-methanol residue (CMR extracted from phase I C. burnetii organisms, a safer Q fever vaccine. These immunized mice had significantly higher levels of IgG1 and IgG2a to rOmpB-4 and interferon-γ (IFN-γ and tumor necrosis factor-α (TNF-α, two crucial cytokines in resisting intracellular bacterial infection, as well as significantly lower rickettsial loads and slighter pathological lesions in organs after challenge with R. rickettsii, compared with mice immunized with rOmpB-4 or CMR alone. Additionally, after challenge with C. burnetii, the coxiella loads in the organs of these mice were significantly lower than those of mice immunized with rOmpB-4 alone. Our results prove that CMR could markedly potentiate enhance the rOmpB-4-specific immunoprotection by promoting specific and non-specific immunoresponses and the immunization with the protective antigen of R. rickettsii combined with CMR of C. burnetii could confer effective protection against infection of R. rickettsii or C. burnetii.

  5. GABA receptor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jong Doo [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2007-04-15

    GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, GABA{sub A}-receptor that allows chloride to pass through a ligand gated ion channel and GABA{sub B}-receptor that uses G-proteins for signaling. The GABA{sub A}-receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate GABA{sub A}-receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with {sup 11}C-FMZ, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, {sup 18}F-fluoroflumazenil (FFMZ) has been developed to overcome {sup 11}C's short half-life. {sup 18}F-FFMZ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using '1{sup 1}C-FMZ PET instead of {sup 18}F-FDG, PET, restrict the foci better and may also help find lesions better than high resolution MR. GABA{sub A} receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, GABA imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas.

  6. GABA receptor imaging

    International Nuclear Information System (INIS)

    Lee, Jong Doo

    2007-01-01

    GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, GABA A -receptor that allows chloride to pass through a ligand gated ion channel and GABA B -receptor that uses G-proteins for signaling. The GABA A -receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate GABA A -receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with 11 C-FMZ, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, 18 F-fluoroflumazenil (FFMZ) has been developed to overcome 11 C's short half-life. 18 F-FFMZ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using '1 1 C-FMZ PET instead of 18 F-FDG, PET, restrict the foci better and may also help find lesions better than high resolution MR. GABA A receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, GABA imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas

  7. Dengue virus receptor

    OpenAIRE

    Hidari, Kazuya I.P.J.; Suzuki, Takashi

    2011-01-01

    Dengue virus is an arthropod-borne virus transmitted by Aedes mosquitoes. Dengue virus causes fever and hemorrhagic disorders in humans and non-human primates. Direct interaction of the virus introduced by a mosquito bite with host receptor molecule(s) is crucial for virus propagation and the pathological progression of dengue diseases. Therefore, elucidation of the molecular mechanisms underlying the interaction between dengue virus and its receptor(s) in both humans and mosquitoes is essent...

  8. Therapeutic androgen receptor ligands

    Science.gov (United States)

    Allan, George F.; Sui, Zhihua

    2003-01-01

    In the past several years, the concept of tissue-selective nuclear receptor ligands has emerged. This concept has come to fruition with estrogens, with the successful marketing of drugs such as raloxifene. The discovery of raloxifene and other selective estrogen receptor modulators (SERMs) has raised the possibility of generating selective compounds for other pathways, including androgens (that is, selective androgen receptor modulators, or SARMs). PMID:16604181

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  10. AMPA receptor ligands

    DEFF Research Database (Denmark)

    Strømgaard, Kristian; Mellor, Ian

    2004-01-01

    Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player...

  11. Angiotensin type 2 receptors

    DEFF Research Database (Denmark)

    Sumners, Colin; de Kloet, Annette D; Krause, Eric G

    2015-01-01

    In most situations, the angiotensin AT2-receptor (AT2R) mediates physiological actions opposing those mediated by the AT1-receptor (AT1R), including a vasorelaxant effect. Nevertheless, experimental evidence vastly supports that systemic application of AT2R-agonists is blood pressure neutral...

  12. Susceptibility of Meningococcal Strains Responsible for Two Serogroup B Outbreaks on U.S. University Campuses to Serum Bactericidal Activity Elicited by the MenB-4C Vaccine.

    Science.gov (United States)

    Rossi, Raffaella; Beernink, Peter T; Giuntini, Serena; Granoff, Dan M

    2015-12-01

    In 2013 and 2014, two U.S. universities had meningococcal serogroup B outbreaks (a total of 14 cases) caused by strains from two different clonal complexes. To control the outbreaks, students were immunized with a serogroup B meningococcal vaccine (Novartis) that was not yet licensed in the United States. The vaccine (referred to as MenB-4C) contains four components capable of eliciting bactericidal activity. Both outbreak strains had high expression levels of two of the vaccine antigens (subfamily B factor H binding protein [FHbp] and neisserial heparin binding antigen [NHba]); the university B outbreak strain also had moderate expression of a third antigen, NadA. We investigated the bactericidal activity of sera from mice immunized with FHbp, NHba, or NadA and sera from MenB-4C-immunized infant macaques and an adult human. The postimmunization bactericidal activity of the macaque or human serum against isolates from university B with FHbp identification (ID) 1 that exactly matched the vaccine FHbp sequence variant was 8- to 21-fold higher than that against isolates from university A with FHbp ID 276 (96% identity to the vaccine antigen). Based on the bactericidal activity of mouse antisera to FHbp, NadA, or NHba and macaque or human postimmunization serum that had been depleted of anti-FHbp antibody, the bactericidal activity against both outbreak strains largely or entirely resulted from antibodies to FHbp. Thus, despite the high level of strain expression of FHbp from a subfamily that matched the vaccine antigen, there can be large differences in anti-FHbp bactericidal activity induced by MenB-4C vaccination. Further, strains with moderate to high NadA and/or NHba expression can be resistant to anti-NadA or anti-NHba bactericidal activity elicited by MenB-4C vaccination. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  13. Report of laboratory and in-situ validation of micro-sensor for monitoring ambient air - Ozone micro-sensors, αSense, model B4 O3 sensors

    OpenAIRE

    SPINELLE LAURENT; GERBOLES Michel; ALEIXANDRE Manuel

    2014-01-01

    The aim of this report was to evaluate and validate O3-B4 sensors of αSense within laboratory and field tests under ambient/indoor air conditions corresponding to a specific micro-environment: traffic station, urban/suburban areas. This report presents the evaluation of the performances and determination of the laboratory and field measurement uncertainty of the sensor values, compared to uncertainties fixed by the Data Quality Objective (DQO) of the European Air Quality Directive for indicat...

  14. Glutamate receptor agonists

    DEFF Research Database (Denmark)

    Vogensen, Stine Byskov; Greenwood, Jeremy R; Bunch, Lennart

    2011-01-01

    The neurotransmitter (S)-glutamate [(S)-Glu] is responsible for most of the excitatory neurotransmission in the central nervous system. The effect of (S)-Glu is mediated by both ionotropic and metabotropic receptors. Glutamate receptor agonists are generally a-amino acids with one or more...... stereogenic centers due to strict requirements in the agonist binding pocket of the activated state of the receptor. By contrast, there are many examples of achiral competitive antagonists. The present review addresses how stereochemistry affects the activity of glutamate receptor ligands. The review focuses...... mainly on agonists and discusses stereochemical and conformational considerations as well as biostructural knowledge of the agonist binding pockets, which is useful in the design of glutamate receptor agonists. Examples are chosen to demonstrate how stereochemistry not only determines how the agonist...

  15. Preparação da Liga Amorfa Co72Nb24B4 como Catalisador na Reação de Oxidação do Metanol

    Directory of Open Access Journals (Sweden)

    Luciano Nascimento

    2015-12-01

    Full Text Available This study aims to investigate and characterize the amorphous alloy Co72Nb24B4 the catalytic oxidation of methanol in products that serve as primary reagents for organic synthesis, such as formaldehyde and other intermediate products. The technique for obtaining the amorphous alloy was electric arc smelting furnace. The amorphous alloy catalyst Co72Nb24B4 was characterized by XRD, SEM / EDS, BET and thermal analysis TGA and DTA. The objective of this work is to develop and study the application of amorphous alloy as catalysts and catalyst supports, due to its thick this oxide layer on its surface capable of oxidizing methanol and intermediates of methanol oxidation reaction. The amorphous alloy structure Co72Nb24B4 is still stable after the catalytic test, since the formation of intermetallic and amorphous phases are rich in active sites that are important for the catalytic processes at the surface of these amorphous materials. DOI: http://dx.doi.org/10.17807/orbital.v7i4.768

  16. Thermal conductivity of layered borides: The effect of building defects on the thermal conductivity of TmAlB4 and the anisotropic thermal conductivity of AlB2

    Directory of Open Access Journals (Sweden)

    X. J. Wang

    2014-04-01

    Full Text Available Rare earth metal borides have attracted great interest due to their unusual properties, such as superconductivity and f-electron magnetism. A recent discovery attributes the tunability of magnetism in rare earth aluminoborides to the effect of so-called “building defects.” In this paper, we report data for the effect of building defects on the thermal conductivities of α-TmAlB4 single crystals. Building defects reduce the thermal conductivity of α-TmAlB4 by ≈30%. At room temperature, the thermal conductivity of AlB2 is nearly a factor of 5 higher than that of α-TmAlB4. AlB2 single crystals are thermally anisotropic with the c-axis thermal conductivity nearly twice the thermal conductivity of the a-b plane. Temperature dependence of the thermal conductivity near and above room temperature reveals that both electrons and phonons contribute substantially to thermal transport in AlB2 with electrons being the dominant heat carriers.

  17. Eu2+-doped Ba2GaB4O9Cl blue-emitting phosphor with high color purity for near-UV-pumped white light-emitting diodes

    Science.gov (United States)

    Gao, Zhiwen; Deng, Huajuan; Xue, Na; Jeong, Jung Hyun; Yu, Ruijin

    2018-01-01

    Eu2+-doped borate fluoride Ba2GaB4O9Cl was synthesized by the conventional high-temperature solid-state reaction. The crystal structure and luminescence properties of the phosphors, as well as their thermal luminescence quenching capabilities and CIE chromaticity coordinates were systematically investigated. Under the excitation at 340 nm, the phosphor exhibited an asymmetric broad-band blue emission with a peak at 445 nm, which is ascribed to the 4f-5d transition of Eu2+. It was further proved that energy transfer among the nearest neighbor ions is the major mechanism for concentration quenching of Eu2+ in Ba2-xGaB4O9Cl:xEu2+ phosphors. The luminescence quenching temperature is 432 K. The CIE color coordinates are very close to those of BaMgAl10O17:Eu2+ (BAM). All the properties indicated that the blue-emitting Ba2GaB4O9Cl:Eu2+ phosphor has potential application in white LEDs.

  18. P2X receptors.

    Science.gov (United States)

    North, R Alan

    2016-08-05

    Extracellular adenosine 5'-triphosphate (ATP) activates cell surface P2X and P2Y receptors. P2X receptors are membrane ion channels preferably permeable to sodium, potassium and calcium that open within milliseconds of the binding of ATP. In molecular architecture, they form a unique structural family. The receptor is a trimer, the binding of ATP between subunits causes them to flex together within the ectodomain and separate in the membrane-spanning region so as to open a central channel. P2X receptors have a widespread tissue distribution. On some smooth muscle cells, P2X receptors mediate the fast excitatory junction potential that leads to depolarization and contraction. In the central nervous system, activation of P2X receptors allows calcium to enter neurons and this can evoke slower neuromodulatory responses such as the trafficking of receptors for the neurotransmitter glutamate. In primary afferent nerves, P2X receptors are critical for the initiation of action potentials when they respond to ATP released from sensory cells such as taste buds, chemoreceptors or urothelium. In immune cells, activation of P2X receptors triggers the release of pro-inflammatory cytokines such as interleukin 1β. The development of selective blockers of different P2X receptors has led to clinical trials of their effectiveness in the management of cough, pain, inflammation and certain neurodegenerative diseases.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. © 2016 The Author(s).

  19. Search for Active-State Conformation of Drug Target GPCR Using Real-Coded Genetic Algorithm

    Science.gov (United States)

    Ishino, Yoko; Harada, Takanori; Aida, Misako

    G-Protein coupled receptors (GPCRs) comprise a large superfamily of proteins and are a target for nearly 50% of drugs in clinical use today. GPCRs have a unique structural motif, seven transmembrane helices, and it is known that agonists and antagonists dock with a GPCR in its ``active'' and ``inactive'' condition, respectively. Knowing conformations of both states is eagerly anticipated for elucidation of drug action mechanism. Since GPCRs are difficult to crystallize, the 3D structures of these receptors have not yet been determined by X-ray crystallography, except the inactive-state conformation of two proteins. The conformation of them enabled the inactive form of other GPCRs to be modeled by computer-aided homology modeling. However, to date, the active form of GPCRs has not been solved. This paper describes a novel method to predict the 3D structure of an active-state GPCR aiming at molecular docking-based virtual screening using real-coded genetic algorithm (real-coded GA), receptor-ligand docking simulations, and molecular dynamics (MD) simulations. The basic idea of the method is that the MD is first used to calculate an average 3D coordinates of all atoms of a GPCR protein against heat fluctuation on the pico- or nano- second time scale, and then real-coded GA involving receptor-ligand docking simulations functions to determine the rotation angle of each helix as a movement on wider time scale. The method was validated using human leukotriene B4 receptor BLT1 as a sample GPCR. Our study demonstrated that the established evolutionary search for the active state of the leukotriene receptor provided the appropriate 3D structure of the receptor to dock with its agonists.

  20. Tomato SlERF.A1, SlERF.B4, SlERF.C3 and SlERF.A3, Members of B3 Group of ERF Family, Are Required for Resistance to Botrytis cinerea.

    Science.gov (United States)

    Ouyang, Zhigang; Liu, Shixia; Huang, Lihong; Hong, Yongbo; Li, Xiaohui; Huang, Lei; Zhang, Yafen; Zhang, Huijuan; Li, Dayong; Song, Fengming

    2016-01-01

    The Ethylene-Responsive Factors (ERFs) comprise a large family of transcriptional factors that play critical roles in plant immunity. Gray mold disease caused by Botrytis cinerea , a typical necrotrophic fungal pathogen, is the serious disease that threatens tomato production worldwide. However, littler is known about the molecular mechanism regulating the immunity to B. cinerea in tomato. In the present study, virus-induced gene silencing (VIGS)-based functional analyses of 18 members of B3 group (also called Group IX) in tomato ERF family were performed to identify putative ERFs that are involved in disease resistance against B. cinerea . VIGS-based silencing of either SlERF.B1 or SlERF.C2 had lethal effect while silencing of SlERF.A3 ( Pit4 ) significantly suppressed vegetative growth of tomato plants. Importantly, silencing of SlERF.A1, SlERF.A3, SlERF.B4 , or SlERF.C3 resulted in increased susceptibility to B. cinerea , attenuated the B. cinerea -induced expression of jasmonic acid/ethylene-mediated signaling responsive defense genes and promoted the B. cinerea -induced H 2 O 2 accumulation. However, silencing of SlERF.A3 also decreased the resistance against Pseudomonas syringae pv. tomato ( Pst ) DC3000 but silencing of SlERF.A1, SlERF.B4 or SlERF.C3 did not affect the resistance to this bacterial pathogen. Expression of SlERF.A1, SlERF.A3, SlERF.B4 , or SlERF.C3 was induced by B. cinerea and by defense signaling hormones such as salicylic acid, methyl jasmonate, and 1-aminocyclopropane-1-carboxylic acid (an ethylene precursor). SlERF.A1, SlERF.B4, SlERF.C3, and SlERF.A3 proteins were found to localize in nucleus of cells and possess transactivation activity in yeasts. These data suggest that SlERF.A1, SlERF.B4, and SlERF.C3, three previously uncharacterized ERFs in B3 group, and SlERF.A3, a previously identified ERF with function in immunity to Pst DC3000, play important roles in resistance against B. cinerea in tomato.

  1. Tomato SlERF.A1, SlERF.B4, SlERF.C3 and SlERF.A3, Members of B3 Group of ERF Family, Are Required for Resistance to Botrytis cinerea

    Science.gov (United States)

    Ouyang, Zhigang; Liu, Shixia; Huang, Lihong; Hong, Yongbo; Li, Xiaohui; Huang, Lei; Zhang, Yafen; Zhang, Huijuan; Li, Dayong; Song, Fengming

    2016-01-01

    The Ethylene-Responsive Factors (ERFs) comprise a large family of transcriptional factors that play critical roles in plant immunity. Gray mold disease caused by Botrytis cinerea, a typical necrotrophic fungal pathogen, is the serious disease that threatens tomato production worldwide. However, littler is known about the molecular mechanism regulating the immunity to B. cinerea in tomato. In the present study, virus-induced gene silencing (VIGS)-based functional analyses of 18 members of B3 group (also called Group IX) in tomato ERF family were performed to identify putative ERFs that are involved in disease resistance against B. cinerea. VIGS-based silencing of either SlERF.B1 or SlERF.C2 had lethal effect while silencing of SlERF.A3 (Pit4) significantly suppressed vegetative growth of tomato plants. Importantly, silencing of SlERF.A1, SlERF.A3, SlERF.B4, or SlERF.C3 resulted in increased susceptibility to B. cinerea, attenuated the B. cinerea-induced expression of jasmonic acid/ethylene-mediated signaling responsive defense genes and promoted the B. cinerea-induced H2O2 accumulation. However, silencing of SlERF.A3 also decreased the resistance against Pseudomonas syringae pv. tomato (Pst) DC3000 but silencing of SlERF.A1, SlERF.B4 or SlERF.C3 did not affect the resistance to this bacterial pathogen. Expression of SlERF.A1, SlERF.A3, SlERF.B4, or SlERF.C3 was induced by B. cinerea and by defense signaling hormones such as salicylic acid, methyl jasmonate, and 1-aminocyclopropane-1-carboxylic acid (an ethylene precursor). SlERF.A1, SlERF.B4, SlERF.C3, and SlERF.A3 proteins were found to localize in nucleus of cells and possess transactivation activity in yeasts. These data suggest that SlERF.A1, SlERF.B4, and SlERF.C3, three previously uncharacterized ERFs in B3 group, and SlERF.A3, a previously identified ERF with function in immunity to Pst DC3000, play important roles in resistance against B. cinerea in tomato. PMID:28083004

  2. OP9 Feeder Cells Are Superior to M2-10B4 Cells for the Generation of Mature and Functional Natural Killer Cells from Umbilical Cord Hematopoietic Progenitors

    Directory of Open Access Journals (Sweden)

    Lara Herrera

    2017-06-01

    Full Text Available Adoptive natural killer (NK cell therapy relies on the acquisition of large numbers of mature and functional NK cells. An option for future immunotherapy treatments is to use large amounts of NK cells derived and differentiated from umbilical cord blood (UCB CD34+ hematopoietic stem cells (HSCs, mainly because UCB is one of the most accessible HSC sources. In our study, we compared the potential of two stromal cell lines, OP9 and M2-10B4, for in vitro generation of mature and functional CD56+ NK cells from UCB CD34+ HSC. We generated higher number of CD56+ NK cells in the presence of the OP9 cell line than when they were generated in the presence of M2-10B4 cells. Furthermore, higher frequency of CD56+ NK cells was achieved earlier when cultures were performed with the OP9 cells than with the M2-10B4 cells. Additionally, we studied in detail the maturation stages of CD56+ NK cells during the in vitro differentiation process. Our data show that by using both stromal cell lines, CD34+ HSC in vitro differentiated into the terminal stages 4–5 of maturation resembled the in vivo differentiation pattern of human NK cells. Higher frequencies of more mature NK cells were reached earlier by using OP9 cell line than M2-10B4 cells. Alternatively, we observed that our in vitro NK cells expressed similar levels of granzyme B and perforin, and there were no significant differences between cultures performed in the presence of OP9 cell line or M2-10B4 cell line. Likewise, degranulation and cytotoxic activity against K562 target cells were very similar in both culture conditions. The results presented here provide an optimal strategy to generate high numbers of mature and functional NK cells in vitro, and point toward the use of the OP9 stromal cell line to accelerate the culture procedure to obtain them. Furthermore, this method could establish the basis for the generation of mature NK cells ready for cancer immunotherapy.

  3. Muscarinic receptor oligomerization.

    Science.gov (United States)

    Marsango, Sara; Ward, Richard J; Alvarez-Curto, Elisa; Milligan, Graeme

    2017-11-14

    G protein-coupled receptors (GPCRs) have been classically described as monomeric entities that function by binding in a 1:1 stoichiometric ratio to both ligand and downstream signalling proteins. However, in recent years, a growing number of studies has supported the hypothesis that these receptors can interact to form dimers and higher order oligomers although the molecular basis for these interactions, the overall quaternary arrangements and the functional importance of GPCR oligomerization remain topics of intense speculation. Muscarinic acetylcholine receptors belong to class A of the GPCR family. Each muscarinic receptor subtype has its own particular distribution throughout the central and peripheral nervous systems. In the central nervous system, muscarinic receptors regulate several sensory, cognitive, and motor functions while, in the peripheral nervous system, they are involved in the regulation of heart rate, stimulation of glandular secretion and smooth muscle contraction. Muscarinic acetylcholine receptors have long been used as a model for the study of GPCR structure and function and to address aspects of GPCR dimerization using a broad range of approaches. In this review, the prevailing knowledge regarding the quaternary arrangement for the various muscarinic acetylcholine receptors has been summarized by discussing work ranging from initial results obtained using more traditional biochemical approaches to those generated with more modern biophysical techniques. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Glutamate receptor agonists

    DEFF Research Database (Denmark)

    Vogensen, Stine Byskov; Greenwood, Jeremy R; Bunch, Lennart

    2011-01-01

    stereogenic centers due to strict requirements in the agonist binding pocket of the activated state of the receptor. By contrast, there are many examples of achiral competitive antagonists. The present review addresses how stereochemistry affects the activity of glutamate receptor ligands. The review focuses...... mainly on agonists and discusses stereochemical and conformational considerations as well as biostructural knowledge of the agonist binding pockets, which is useful in the design of glutamate receptor agonists. Examples are chosen to demonstrate how stereochemistry not only determines how the agonist...

  5. P2X receptors

    OpenAIRE

    North, R. Alan

    2016-01-01

    Extracellular adenosine 5′-triphosphate (ATP) activates cell surface P2X and P2Y receptors. P2X receptors are membrane ion channels preferably permeable to sodium, potassium and calcium that open within milliseconds of the binding of ATP. In molecular architecture, they form a unique structural family. The receptor is a trimer, the binding of ATP between subunits causes them to flex together within the ectodomain and separate in the membrane-spanning region so as to open a central channel. P2...

  6. Serotonin Receptors in Hippocampus

    Science.gov (United States)

    Berumen, Laura Cristina; Rodríguez, Angelina; Miledi, Ricardo; García-Alcocer, Guadalupe

    2012-01-01

    Serotonin is an ancient molecular signal and a recognized neurotransmitter brainwide distributed with particular presence in hippocampus. Almost all serotonin receptor subtypes are expressed in hippocampus, which implicates an intricate modulating system, considering that they can be localized as autosynaptic, presynaptic, and postsynaptic receptors, even colocalized within the same cell and being target of homo- and heterodimerization. Neurons and glia, including immune cells, integrate a functional network that uses several serotonin receptors to regulate their roles in this particular part of the limbic system. PMID:22629209

  7. Somatostatin receptor skintigrafi

    DEFF Research Database (Denmark)

    Rasmussen, Karin; Nielsen, Jørn Theil; Rehling, Michael

    2005-01-01

    Somatostatin receptor scintigraphy (SRS) is a very valuable imaging technique for visualisation of a diversity of neuroendocrine tumours. The sensitivity for localisation of carcinoid tumours is high, but somewhat lower for other neuroendocrine tumours. The methodology, multiple clinical aspects ...

  8. Muscarinic receptor oligomerization

    OpenAIRE

    Marsango, Sara; Ward, Richard J.; Alvarez-Curto, Elisa; Milligan, Graeme

    2017-01-01

    G protein-coupled receptors (GPCRs) have been classically described as monomeric entities that function by binding in a 1:1 stoichiometric ratio to both ligand and downstream signalling proteins. However, in recent years, a growing number of studies has supported the hypothesis that these receptors can interact to form dimers and higher order oligomers although the molecular basis for these interactions, the overall quaternary arrangements and the functional importance of GPCR oligomerization...

  9. Adenosine receptor neurobiology: overview.

    Science.gov (United States)

    Chen, Jiang-Fan; Lee, Chien-fei; Chern, Yijuang

    2014-01-01

    Adenosine is a naturally occurring nucleoside that is distributed ubiquitously throughout the body as a metabolic intermediary. In the brain, adenosine functions as an important upstream neuromodulator of a broad spectrum of neurotransmitters, receptors, and signaling pathways. By acting through four G-protein-coupled receptors, adenosine contributes critically to homeostasis and neuromodulatory control of a variety of normal and abnormal brain functions, ranging from synaptic plasticity, to cognition, to sleep, to motor activity to neuroinflammation, and cell death. This review begun with an overview of the gene and genome structure and the expression pattern of adenosine receptors (ARs). We feature several new developments over the past decade in our understanding of AR functions in the brain, with special focus on the identification and characterization of canonical and noncanonical signaling pathways of ARs. We provide an update on functional insights from complementary genetic-knockout and pharmacological studies on the AR control of various brain functions. We also highlight several novel and recent developments of AR neurobiology, including (i) recent breakthrough in high resolution of three-dimension structure of adenosine A2A receptors (A2ARs) in several functional status, (ii) receptor-receptor heterodimerization, (iii) AR function in glial cells, and (iv) the druggability of AR. We concluded the review with the contention that these new developments extend and strengthen the support for A1 and A2ARs in brain as therapeutic targets for neurologic and psychiatric diseases. © 2014 Elsevier Inc. All rights reserved.

  10. Genetics of taste receptors.

    Science.gov (United States)

    Bachmanov, Alexander A; Bosak, Natalia P; Lin, Cailu; Matsumoto, Ichiro; Ohmoto, Makoto; Reed, Danielle R; Nelson, Theodore M

    2014-01-01

    Taste receptors function as one of the interfaces between internal and external milieus. Taste receptors for sweet and umami (T1R [taste receptor, type 1]), bitter (T2R [taste receptor, type 2]), and salty (ENaC [epithelial sodium channel]) have been discovered in the recent years, but transduction mechanisms of sour taste and ENaC-independent salt taste are still poorly understood. In addition to these five main taste qualities, the taste system detects such noncanonical "tastes" as water, fat, and complex carbohydrates, but their reception mechanisms require further research. Variations in taste receptor genes between and within vertebrate species contribute to individual and species differences in taste-related behaviors. These variations are shaped by evolutionary forces and reflect species adaptations to their chemical environments and feeding ecology. Principles of drug discovery can be applied to taste receptors as targets in order to develop novel taste compounds to satisfy demand in better artificial sweeteners, enhancers of sugar and sodium taste, and blockers of bitterness of food ingredients and oral medications.

  11. Ordering effects in benzo[1,2-b:4,5-b']difuran-thieno[3,4-c]pyrrole-4,6- dione polymers with >7% solar cell efficiency

    KAUST Repository

    Warnan, Julien

    2014-05-15

    Benzo[1,2-b:4,5-b\\']difuran-thieno[3,4-c]pyrrole-4,6-dione (PBDFTPD) polymers prepared by microwave-assisted synthesis can achieve power conversion efficiencies (PCEs) >7% in bulk-heterojunction solar cells with phenyl-C61/71-butyric acid methyl ester (PCBM). In "as-cast" PBDFTPD-based devices solution-processed without a small-molecule additive, high PCEs can be obtained in spite of the weak propensity of the polymers to self-assemble and form π-aggregates in thin films. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Unifying Dynamic Prognostic Phenology, Heterogeneous Soil and Vegetation Fluxes, and Ecosystem Biomass and Carbon Stocks To Predict the Terrestrial Carbon Cycle and Land-Atmosphere Exchanges in the Simple Biosphere Model (SiB4)

    Science.gov (United States)

    Haynes, K. D.; Baker, I. T.; Denning, S.

    2016-12-01

    Future climate projections require process-based models that incorporate the mechanisms and feedbacks controlling the carbon cycle. Over the past three decades, land surface models have been key contributors to Earth system models, evolving from predicting latent (LE) and sensible (SH) heat fluxes to energy and water budgets, momentum transfer, and terrestrial carbon exchange and storage. This study presents the latest version of the Simple Biosphere Model (SiB4), which builds on a compilation of previous versions and adds a new mechanistic-based scheme that fully predicts the terrestrial carbon cycle. The main SiB4 updates can be summarized as follows: (i) Incorporation of carbon pools that use new respiration and transfer methods, (ii) Creation of a new dynamic phenology scheme that uses mechanistic-based seasonal stages, and (iii) Unification of carbon pools, phenology and disturbance to close the carbon cycle. SiB4 removes the dependence on satellite-based vegetation indices, and instead uses a single mathematical framework to prognose self-consistent land-atmosphere exchanges of carbon, water, energy, radiation, and momentum, as well as carbon storage. Since grasslands cover 30% of land and are highly seasonal, we investigated forty grass sites. Diurnal cycles of gross primary productivity (GPP), ecosystem respiration (RE), net ecosystem exchange (NEE), LE and SH have third-quartile root mean squared (RMS) errors less than 2.0 µmol m-2 s-1, 1.9 µmol m-2 s-1, 2.0 µmol m-2 s-1, 42 W m-2, and 78 W m-2, respectively. On the synoptic timeframe, all sites have significant LE correlation coefficients of non-seasonal daily data; and all but one have significant SH correlations. Mean seasonal cycles for leaf area index (LAI), GPP, RE, LE, and SH have third-quartile normalized RMS errors less than 32%, 25%, 28%, 16%, and 48%, respectively. On multi-year timescales, daily correlations of LAI, GPP, RE, and LE are all statistically significant, with third-quartile RMS

  13. Predicting prostate cancer-specific outcome after radical prostatectomy among men with very high-risk cT3b/4 PCa: a multi-institutional outcome study of 266 patients.

    Science.gov (United States)

    Moltzahn, F; Karnes, J; Gontero, P; Kneitz, B; Tombal, B; Bader, P; Briganti, A; Montorsi, F; Van Poppel, H; Joniau, S; Spahn, M

    2015-03-01

    The value of radical prostatectomy (RP) as an approach for very high-risk prostate cancer (PCa) patients is controversial. To examine the risk of 10-year cancer-specific mortality (CSM) and other-cause mortality (OCM) according to clinical and pathological characteristics of very high-risk cT3b/4 PCa patients treated with RP as the primary treatment option. In a multi-institutional cohort, 266 patients with very high-risk cT3b/4 PCa treated with RP were identified. All patients underwent RP and pelvic lymph-node dissection. Competing-risk analyses assessed 10-year CSM and OCM before and after stratification for age and Charlson comorbidity index (CCI). Overall, 34 (13%) patients died from PCa and 73 (28%) from OCM. Ten-year CSM and OCM rates ranged from 5.6% to 12.9% and from 10% to 38%, respectively. OCM was the leading cause of death in all subgroups. Age and comorbidities were the main determinants of OCM. In healthy men, CSM rate did not differ among age groups (10-year CSM rate for ⩽64, 65-69 and ⩾70 years: 16.2%, 11.5% and 17.1%, respectively). Men with a CCI ⩾1 showed a very low risk of CSM irrespective of age (10-year CSM: 5.6-6.1%), whereas the 10-year OCM rates increased with age up to 38% in men ⩾70 years. Very high-risk cT3b/4 PCa represents a heterogeneous group. We revealed overall low CSM rates despite the highly unfavorable clinical disease. For healthy men, CSM was independent of age, supporting RP even for older men. Conversely, less healthy patients had the highest risk of dying from OCM while sharing very low risk of CSM, indicating that this group might not benefit from an aggressive surgical treatment. Outcome after RP as the primary treatment option in cT3b/4 PCa patients is related to age and comorbidity status.

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

    Science.gov (United States)

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

    2016-01-01

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

  15. Ir-LBP, an ixodes ricinus tick salivary LTB4-binding lipocalin, interferes with host neutrophil function.

    Directory of Open Access Journals (Sweden)

    Jérôme Beaufays

    Full Text Available BACKGROUND: During their blood meal, ticks secrete a wide variety of proteins that can interfere with their host's defense mechanisms. Among these proteins, lipocalins play a major role in the modulation of the inflammatory response. METHODOLOGY/PRINCIPAL FINDINGS: We previously identified 14 new lipocalin genes in the tick Ixodes ricinus. One of them codes for a protein that specifically binds leukotriene B4 with a very high affinity (Kd: +/-1 nM, similar to that of the neutrophil transmembrane receptor BLT1. By in silico approaches, we modeled the 3D structure of the protein and the binding of LTB4 into the ligand pocket. This protein, called Ir-LBP, inhibits neutrophil chemotaxis in vitro and delays LTB4-induced apoptosis. Ir-LBP also inhibits the host inflammatory response in vivo by decreasing the number and activation of neutrophils located at the tick bite site. Thus, Ir-LBP participates in the tick's ability to interfere with proper neutrophil function in inflammation. CONCLUSIONS/SIGNIFICANCE: These elements suggest that Ir-LBP is a "scavenger" of LTB4, which, in combination with other factors, such as histamine-binding proteins or proteins inhibiting the classical or alternative complement pathways, permits the tick to properly manage its blood meal. Moreover, with regard to its properties, Ir-LBP could possibly be used as a therapeutic tool for illnesses associated with an increased LTB4 production.

  16. TSCA Section 5(b)(4) Concern List

    Science.gov (United States)

    EPA's existing chemicals programs address pollution prevention, risk assessment, hazard and exposure assessment and/or characterization, and risk management for chemicals substances in commercial use.

  17. 45 CFR 73b.4 - Proceedings.

    Science.gov (United States)

    2010-10-01

    ... a former departmental employee fails to appeal from an adverse initial decision within the... issue an order: (i) Prohibiting the former departmental employee from making, on behalf of any other... DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION DEBARMENT OR SUSPENSION OF FORMER EMPLOYEES...

  18. Lifetime-broadening-suppressed X-ray absorption spectrum of β-YbAlB4 deduced from Yb 3d → 2p resonant X-ray emission spectroscopy

    International Nuclear Information System (INIS)

    Kawamura, Naomi; Mizumaki, Masaichiro; Kanai, Noriko; Hayashi, Hisashi; Matsuda, Yasuhiro H.; Kuga, Kentaro; Nakatsuji, Satoru; Watanabe, Shinji

    2017-01-01

    In this work, the Yb 3d → 2p (Yb Lα 1,2 ) resonant X-ray emission spectrum of β-YbAlB 4 was acquired using excitation energies around the Yb L 3 -edge, at 2 K. Subsequently, the lifetime-broadening-suppressed (LBS) X-ray absorption structure (XAS) spectrum was obtained using the SIM-RIXS program. This spectrum was found to exhibit clearly resolved pre-edge and shoulder structures. Resonant Lα 1 emission spectra were well reproduced from LBS-XAS profiles over wide ranges of excitation and emission energies. In contrast, noticeable discrepancies appeared between the experimental and simulated Lα 2 emission spectra, suggesting an effect resulting from M 4 M 5 O 1 Coster-Kronig transitions. LBS-XAS, in conjunction with partial fluorescence yield (PFY) XAS and transmission XAS, determined a value for the Yb valence (v) in β-YbAlB 4 of 2.76 ± 0.08 at 2 K. Despite this relatively large uncertainty in v, each method provided a consistent variation in valence (δv) as the temperature was raised from 2 to 280 K: 0.060 ± 0.004 (LBS-XAS), 0.061 ± 0.005 (PFY-XAS) and 0.058 ± 0.007 (transmission XAS). The smaller δv associated with LBS-XAS demonstrates the greater precision of this method. (author)

  19. A case report of fulminant type 1 diabetes mellitus associated with drug-induced hypersensitivity syndrome in an elderly patient with coxsackie B4 virus infection and human leukocyte antigen-A24 haplotype.

    Science.gov (United States)

    Takeno, Ayumu; Kanazawa, Ippei; Morita, Miwa; Takedani, Kai; Miyake, Hitomi; Yamamoto, Masahiro; Nogami, Kyoko; Kaneko, Sakae; Sugimoto, Toshitsugu

    2018-01-30

    Drug-induced hypersensitivity syndrome (DIHS) is a severe systemic adverse drug reaction. Previous studies showed that DIHS is associated with the onset of fulminant type 1 diabetes mellitus (FT1D). Although genetic background and abnormalities in immune response or viral infection are considered to be associated with pathogenesis of FT1D, it remains unclear whether virus infection and specific human leukocyte antigen (HLA) typing are involved in DIHS-associated FT1D. Here, we report a case of a 78-year-old female patient with FT1D after DIHS treatment. She was diagnosed as DIHS caused by carbamazepine, and treatment with predonisolone was initiated. After 46 days from the occurrence of DIHS, she was admitted to our hospital because of type 1 diabetes mellitus and diabetic ketoacidosis. Although her Hemoglobin A1c (HbA1c) was elevated by predonisolone treatment (HbA1c: 9.2%), we diagnosed her as fulminant type 1 diabetes mellitus considering the abrupt onset of the ketoacidosis. Her general condition was improved by treatment with fluid infusion and insulin administration. During her clinical course, the infection of coxsackie B4 virus was observed. In addition, the examination of HLA typing showed HLA-A24 haplotype. These findings suggest that the coxsackie B4 virus infection may be involved in the pathogenesis of DIHS-induced FT1D, and that HLA-A24 haplotype might relate to DIHS-associated FT1D.

  20. Ionotropic crustacean olfactory receptors.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Corey

    Full Text Available The nature of the olfactory receptor in crustaceans, a major group of arthropods, has remained elusive. We report that spiny lobsters, Panulirus argus, express ionotropic receptors (IRs, the insect chemosensory variants of ionotropic glutamate receptors. Unlike insects IRs, which are expressed in a specific subset of olfactory cells, two lobster IR subunits are expressed in most, if not all, lobster olfactory receptor neurons (ORNs, as confirmed by antibody labeling and in situ hybridization. Ligand-specific ORN responses visualized by calcium imaging are consistent with a restricted expression pattern found for other potential subunits, suggesting that cell-specific expression of uncommon IR subunits determines the ligand sensitivity of individual cells. IRs are the only type of olfactory receptor that we have detected in spiny lobster olfactory tissue, suggesting that they likely mediate olfactory signaling. Given long-standing evidence for G protein-mediated signaling in activation of lobster ORNs, this finding raises the interesting specter that IRs act in concert with second messenger-mediated signaling.

  1. ErbB2 resembles an autoinhibited invertebrate epidermal growth factor receptor

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-09-25

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

  2. Role of ErbB receptors in cancer cell migration and invasion

    Directory of Open Access Journals (Sweden)

    Aline eAppert-Collin

    2015-11-01

    Full Text Available Growth factors mediate their diverse biologic responses (regulation of cellular proliferation, differentiation, migration and survival by binding to and activating cell-surface receptors with intrinsic protein kinase activity named Receptor Tyrosine Kinases (RTKs. About 60 RTKs have been identified and can be classified into more than 16 different receptor families. Their activity is normally tightly controlled and regulated. Overexpression of RTK proteins or functional alterations caused by mutations in the corresponding genes or abnormal stimulation by autocrine growth factor loops contribute to constitutive RTK signaling, resulting in alterations in the physiological activities of cells. The ErbB receptor family of RTKs comprises four distinct receptors: the EGFR (also known as ErbB1/HER1, ErbB2 (neu, HER2, ErbB3 (HER3 and ErbB4 (HER4. ErbB family members are often overexpressed, amplified, or mutated in many forms of cancer, making them important therapeutic targets. EGFR has been found to be amplified in gliomas and non-small-cell lung carcinoma while ErbB2 amplifications are seen in breast, ovarian, bladder, non-small-cell lung carcinoma, as well as several other tumor types. Several data have shown that ErbB receptor family and its downstream pathway regulate epithelial-mesenchymal transition, migration, and tumor invasion by modulating extracellular matrix components. Recent findings indicate that extracellular matrix components such as matrikines bind specifically to EGF receptor and promote cell invasion. In this review, we will present an in-depth overview of the structure, mechanisms, cell signaling, and functions of ErbB family receptors in cell adhesion and migration. Furthermore, we will describe in a last part the new strategies developed in anti-cancer therapy to inhibit ErbB family receptor activation.

  3. adrenergic receptor with preeclampsia

    African Journals Online (AJOL)

    User

    2011-05-09

    May 9, 2011 ... expenditure and lipolysis. The mechanisms underlying lipolytic resistance to catecholamines in obesity are not clear and may include desensitization of ADRB2 function. (Yamada et al., 1999). Many studies have reported on the relationship between obesity and genetic variants in β-2 adrenergic receptors ...

  4. Ginkgolides and glycine receptors

    DEFF Research Database (Denmark)

    Jaracz, Stanislav; Nakanishi, Koji; Jensen, Anders A.

    2004-01-01

    Ginkgolides from the Ginkgo biloba tree are diterpenes with a cage structure consisting of six five-membered rings and a unique tBu group. They exert a variety of biological properties. In addition to being antagonists of the platelet activating factor receptor (PAFR), it has recently been shown ...

  5. Meeting report: nuclear receptors

    DEFF Research Database (Denmark)

    Tuckermann, Jan; Bourguet, William; Mandrup, Susanne

    2010-01-01

    The biannual European Molecular Biology Organization (EMBO) conference on nuclear receptors was organized by Beatrice Desvergne and Laszlo Nagy and took place in Cavtat near Dubrovnik on the Adriatic coast of Croatia September 25-29, 2009. The meeting brought together researchers from all over...

  6. Metformin and insulin receptors

    International Nuclear Information System (INIS)

    Vigneri, R.; Gullo, D.; Pezzino, V.

    1984-01-01

    The authors evaluated the effect of metformin (N,N-dimethylbiguanide), a biguanide known to be less toxic than phenformin, on insulin binding to its receptors, both in vitro and in vivo. Specific 125 I-insulin binding to cultured IM-9 human lymphocytes and MCF-7 human breast cancer cells was determined after preincubation with metformin. Specific 125 I-insulin binding to circulating monocytes was also evaluated in six controls, eight obese subjects, and six obese type II diabetic patients before and after a short-term treatment with metformin. Plasma insulin levels and blood glucose were also measured on both occasions. Metformin significantly increased insulin binding in vitro to both IM-9 lymphocytes and MCF-7 cells; the maximum increment was 47.1% and 38.0%, respectively. Metformin treatment significantly increased insulin binding in vivo to monocytes of obese subjects and diabetic patients. Scatchard analysis indicated that the increased binding was mainly due to an increase in receptor capacity. Insulin binding to monocytes of normal controls was unchanged after metformin as were insulin levels in all groups; blood glucose was significantly reduced after metformin only in diabetic patients. These data indicate that metformin increases insulin binding to its receptors in vitro and in vivo. The effect in vivo is observed in obese subjects and in obese type II diabetic patients, paralleling the clinical effectiveness of this antidiabetic agent, and is not due to receptor regulation by circulating insulin, since no variation in insulin levels was recorded

  7. Donor and Acceptor Unit Sequences Influence Material Performance in Benzo[1,2-b:4,5-b′]dithiophene-6,7-Difluoroquinoxaline Small Molecule Donors for BHJ Solar Cells

    KAUST Repository

    Wang, Kai

    2016-08-22

    Well-defined small molecule (SM) donors can be used as alternatives to π-conjugated polymers in bulk-heterojunction (BHJ) solar cells with fullerene acceptors (e.g., PC61/71BM). Taking advantage of their synthetic tunability, combinations of various donor and acceptor motifs can lead to a wide range of optical, electronic, and self-assembling properties that, in turn, may impact material performance in BHJ solar cells. In this report, it is shown that changing the sequence of donor and acceptor units along the π-extended backbone of benzo[1,2-b:4,5-b\\']dithiophene-6,7-difluoroquinoxaline SM donors critically impacts (i) molecular packing, (ii) propensity to order and preferential aggregate orientations in thin-films, and (iii) charge transport in BHJ solar cells. In these systems (SM1-3), it is found that 6,7-difluoroquinoxaline ([2F]Q) motifs directly appended to the central benzo[1,2-b:4,5-b\\']dithiophene (BDT) unit yield a lower-bandgap analogue (SM1) with favorable molecular packing and aggregation patterns in thin films, and optimized BHJ solar cell efficiencies of ≈6.6%. 1H-1H DQ-SQ NMR analyses indicate that SM1 and its counterpart with [2F]Q motifs substituted as end-group SM3 possess distinct self-assembly patterns, correlating with the significant charge transport and BHJ device efficiency differences observed for the two analogous SM donors (avg. 6.3% vs 2.0%, respectively). © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. [Impact of anemia correction on the production of the circulating morphogenetic protein α-Klotho in patients with Stages 3B-4 chronic kidney disease: A new direction of cardionephroprotection].

    Science.gov (United States)

    Milovanov, Yu S; Mukhin, N A; Kozlovskaya, L V; Milovanova, S Yu; Markina, M M

    2016-01-01

    To investigate the impact of anemia correction with erythropoiesis stimulants on the serum level of the circulating morphogenetic protein α-Klotho in patients with Stages 3B--4 chronic kidney disease (CKD). 64 patients aged 42±8 years with Stages 3B--4 nondiabetic CKD were examined and divided into 2 groups: 1) 32 patients with anemia (the target hemoglobin levels could be achieved and kept with erythropoietin and iron saccharate in 20 patients (Group A) and those could not be done in 12 patients (Group 1B). A control group (Group 2) consisted of 32 non-anemic patients matched for gender, age, and degree of a glomerular filtration rate (GFR) reduction. Along with iron exchange indicators, the time course of changes in serum Klotho levels were examined in all the 64 patients during screening and one year after the end of the study. For correction of anemia, 32 patients with this condition (Groups 1A and 1B) took short-acting epoetin (hypodermic recormon 2,000 IU thrice per week + iron (intravenous venofer 5 ml of 100 mg once per week)) under control of hemoglobin levels and serum transferrin iron and ferritin saturation. After achieving the target hemoglobin level of 110-120 g/l, for its keeping, all the patients received, instead of short-acting epoetin, long-acting hypodermic darbepoetin-α 1.5 µg once every 2 months and intravenous iron saccharate 100 mg once every 2 weeks. Among the 32 anemic patients in Group 1, 20 (63%) (Group 1 A) could achieve the target hemoglobin level (110--120 g/l) and maintain it within this range, by performing therapy with epoitin-β + iron saccharate; anemia (the hemoglobin level of anemia, left ventricular hypertrophy, and heart failure), but also a pathogenetic factor of CKD progression. Anemia correction with erythropoiesis stimulants has been shown to enhance the renal and extrarenal production of α-Klotho.

  9. Angiotensin type 2 receptor (AT2R) and receptor Mas

    DEFF Research Database (Denmark)

    Villela, Daniel; Leonhardt, Julia; Patel, Neal

    2015-01-01

    The angiotensin type 2 receptor (AT2R) and the receptor Mas are components of the protective arms of the renin-angiotensin system (RAS), i.e. they both mediate tissue protective and regenerative actions. The spectrum of actions of these two receptors and their signalling mechanisms display striking...... the phenomenon of blockade of angiotensin-(1-7) [Ang-(1-7)] actions by AT2R antagonists and vice versa. Such mechanisms may comprise dimerization of the receptors or dimerization-independent mechanisms such as lack of specificity of the receptor ligands used in the experiments or involvement of the Ang-(1...

  10. Novel Strategies for the Treatment of Estrogen Receptor-Negative Breast Cancer

    Science.gov (United States)

    2009-04-01

    specific protein tyrosine kinase chemokine (C-C motif) ligand 4 pyridoxal (pyridoxine, vitamin B6 ) kinase v-yes-1 NM_003263 NM_006785 NM_004226...pyridoxine, vitamin B6 ) kinas EPH receptor B4 phosphatidylinositol 4-kinase, catalytic v-raf-1 murine leukemia viral oncogene phosphoribosyl pyrophosphate...specific proteins  in complex samples.   Recent advances  in  163 robotics and  antibody   production  have allowed for proteomic arrays to subgroup

  11. Prostaglandin Receptor Signaling in Disease

    Directory of Open Access Journals (Sweden)

    Toshiyuki Matsuoka

    2007-01-01

    Full Text Available Prostanoids, consisting of the prostaglandins (PGs and the thromboxanes (TXs, are a group of lipid mediators formed in response to various stimuli. They include PGD2, PGE2, PGF2α, PGI2, and TXA2. They are released outside of the cells immediately after synthesis, and exert their actions by binding to a G-protein coupled rhodopsin-type receptor on the surface of target cells. There are eight types of the prostanoid receptors conserved in mammals from mouse to human. They are the PGD receptor (DP, four subtypes of the PGE receptor (EP1, EP2, EP3, and EP4, the PGF receptor (FP, PGI receptor (IP, and TXA receptor (TP. Recently, mice deficient in each of these prostanoid receptors were generated and subjected to various experimental models of disease. These studies have revealed the roles of PG receptor signaling in various pathological conditions, and suggest that selective manipulation of the prostanoid receptors may be beneficial in treatment of the pathological conditions. Here we review these recent findings of roles of prostanoid receptor signaling and their therapeutic implications.

  12. Receptors for enterovirus 71.

    Science.gov (United States)

    Yamayoshi, Seiya; Fujii, Ken; Koike, Satoshi

    2014-07-01

    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 critical roles in attachment, viral entry and uncoating, and it can facilitate efficient EV71 infection. The three-dimensional structures of the mature EV71 virion, procapsid and empty capsid, as well as the exofacial domain of SCARB2, have been elucidated. This structural information has greatly increased our understanding of the early steps of EV71 infection. Furthermore, SCARB2 plays essential roles in the development of EV71 neurological disease in vivo. Adult mice are not susceptible to infection by EV71, but transgenic mice that express human SCARB2 become susceptible to EV71 infection and develop similar neurological diseases to those found in humans. This mouse model facilitates the in vivo investigation of many issues related to EV71. PSGL-1, sialylated glycan, heparan sulfate and Anx2 are attachment receptors, which enhance viral infection by retaining the virus on the cell surface. These molecules also contribute to viral infection in vitro either by interacting with SCARB2 or independently of SCARB2. However, the cooperative effects of these receptors, and their contribution to EV71 pathogenicity in vivo, remain to be elucidated.

  13. The interleukin-4 receptor: signal transduction by a hematopoietin receptor.

    Science.gov (United States)

    Keegan, A D; Pierce, J H

    1994-02-01

    Over the last several years, the receptors for numerous cytokines have been molecularly characterized. Analysis of their amino acid sequences shows that some of these receptors bear certain motifs in their extracellular domains that define a family of receptors called the Hematopoietin receptor superfamily. Significant advances in characterizing the structure, function, and mechanisms of signal transduction have been made for several members of this family. The purpose of this review is to discuss the recent advances made for one of the family members, the interleukin (IL) 4 receptor. Other receptor systems have recently been reviewed elsewhere. The IL-4 receptor consists of, at the minimum, the cloned 140 kDa IL-4-binding chain with the potential for associating with other chains. The IL-4 receptor transduces its signal by activating a tyrosine kinase that phosphorylates cellular substrates, including the receptor itself, and the 170 kDa substrate called 4PS. Phosphorylated 4PS interacts with the SH2 domain of the enzyme PI-3'-kinase and increases its enzymatic activity. These early events in the IL-4 receptor initiated signaling pathway may trigger a series of signals that will ultimately lead to an IL-4 specific biologic outcome.

  14. Evolutionary analysis of functional divergence among chemokine receptors, decoy receptors and viral receptors

    Directory of Open Access Journals (Sweden)

    Hiromi eDaiyasu

    2012-07-01

    Full Text Available Chemokine receptors (CKRs function in the inflammatory response and in vertebrate homeostasis. Decoy and viral receptors are two types of CKR homologues with modified functions from those of the typical CKRs. The decoy receptors are able to bind ligands without signaling. On the other hand, the viral receptors show constitutive signaling without ligands. We examined the sites related to the functional difference. At first, the decoy and viral receptors were each classified into five groups, based on the molecular phylogenetic analysis. A multiple amino acid sequence alignment between each group and the CKRs was then constructed. The difference in the amino acid composition between the group and the CKRs was evaluated as the Kullback-Leibler (KL information value at each alignment site. The KL information value is considered to reflect the difference in the functional constraints at the site. The sites with the top 5% of KL information values were selected and mapped on the structure of a CKR. The comparisons with decoy receptor groups revealed that the detected sites were biased on the intracellular side. In contrast, the sites detected from the comparisons with viral receptor groups were found on both the extracellular and intracellular sides. More sites were found in the ligand-binding pocket in the analyses of the viral receptor groups, as compared to the decoy receptor groups. Some of the detected sites were located in the GPCR motifs. For example, the DRY motif of the decoy receptors was often degraded, although the motif of the viral receptors was basically conserved. The observations for the viral receptor groups suggested that the constraints in the pocket region are loose and that the sites on the intracellular side are different from those for the decoy receptors, which may be related to the constitutive signaling activity of the viral receptors.

  15. Melatonin Receptor Genes in Vertebrates

    Directory of Open Access Journals (Sweden)

    Hua Dong Yin

    2013-05-01

    Full Text Available Melatonin receptors are members of the G protein-coupled receptor (GPCR family. Three genes for melatonin receptors have been cloned. The MT1 (or Mel1a or MTNR1A and MT2 (or Mel1b or MTNR1B receptor subtypes are present in humans and other mammals, while an additional melatonin receptor subtype, Mel1c (or MTNR1C, has been identified in fish, amphibians and birds. Another melatonin related orphan receptor, GPR50, which does not bind melatonin, is found exclusively in mammals. The hormone melatonin is secreted primarily by the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone acts systemically in numerous organs. In the brain, it is involved in the regulation of various neural and endocrine processes, and it readjusts the circadian pacemaker, the suprachiasmatic nucleus. This article reviews recent studies of gene organization, expression, evolution and mutations of melatonin receptor genes of vertebrates. Gene polymorphisms reveal that numerous mutations are associated with diseases and disorders. The phylogenetic analysis of receptor genes indicates that GPR50 is an outgroup to all other melatonin receptor sequences. GPR50 may have separated from a melatonin receptor ancestor before the split between MTNR1C and the MTNR1A/B ancestor.

  16. Effects of Perioperative Supplementation with Omega-3 Fatty Acids on Leukotriene B4 and Leukotriene B5 Production by Stimulated Neutrophils in Patients with Colorectal Cancer: A Randomized, Placebo-Controlled Intervention Trial

    Directory of Open Access Journals (Sweden)

    Lone S. Sorensen

    2014-09-01

    Full Text Available Omega-3 fatty acids (n-3 FA may have beneficial clinical and immune-modulating effects in surgical patients. In a randomized, double-blind, prospective, placebo-controlled trial, 148 patients referred for elective colorectal cancer surgery received an n-3 FA-enriched oral nutritional supplement (ONS providing 2.0 g of eicosapentaenoic acid (EPA and 1.0 g of docosahexaenoic acid (DHA per day or a standard ONS for seven days before surgery. On the day of operation, there was a significant increase in the production of leukotriene B5 (LTB5 (p < 0.01 and 5-hydroxyeicosapentaenoic acid (5-HEPE (p < 0.01, a significant decrease in the production of leukotriene B4 (LTB4 (p < 0.01 and a trend for a decrease in the production of 5-hydroxyeicosatetraenoic acid (5-HETE (p < 0.1 from stimulated neutrophils in the active group compared with controls. There was no association between LTB4 values and postoperative complications. In conclusion, oral n-3 FA exerts anti-inflammatory effects in surgical patients, without reducing the risk of postoperative complications.

  17. Linear side chains in benzo[1,2-b:4,5-b′]dithiophene-thieno[3,4-c] pyrrole-4,6-dione polymers direct self-assembly and solar cell performance

    KAUST Repository

    Cabanetos, Clement

    2013-03-27

    While varying the size and branching of solubilizing side chains in π-conjugated polymers impacts their self-assembling properties in thin-film devices, these structural changes remain difficult to anticipate. This report emphasizes the determining role that linear side-chain substituents play in poly(benzo[1,2-b:4,5-b′]dithiophene-thieno[3,4-c]pyrrole-4,6-dione) (PBDTTPD) polymers for bulk heterojunction (BHJ) solar cell applications. We show that replacing branched side chains by linear ones in the BDT motifs induces a critical change in polymer self-assembly and backbone orientation in thin films that correlates with a dramatic drop in solar cell efficiency. In contrast, we show that for polymers with branched alkyl-substituted BDT motifs, controlling the number of aliphatic carbons in the linear N-alkyl-substituted TPD motifs is a major contributor to improved material performance. With this approach, PBDTTPD polymers were found to reach power conversion efficiencies of 8.5% and open-circuit voltages of 0.97 V in BHJ devices with PC71BM, making PBDTTPD one of the best polymer donors for use in the high-band-gap cell of tandem solar cells. © 2013 American Chemical Society.

  18. Flavivirus Entry Receptors: An Update

    Directory of Open Access Journals (Sweden)

    Manuel Perera-Lecoin

    2013-12-01

    Full Text Available Flaviviruses enter host cells by endocytosis initiated when the virus particles interact with cell surface receptors. The current model suggests that flaviviruses use at least two different sets of molecules for infectious entry: attachment factors that concentrate and/or recruit viruses on the cell surface and primary receptor(s that bind to virions and direct them to the endocytic pathway. Here, we present the currently available knowledge regarding the flavivirus receptors described so far with specific attention to C-type lectin receptors and the phosphatidylserine receptors, T-cell immunoglobulin and mucin domain (TIM and TYRO3, AXL and MER (TAM. Their role in flavivirus attachment and entry as well as their implication in the virus biology will be discussed in depth.

  19. Dimerization of nuclear receptors.

    Science.gov (United States)

    Germain, Pierre; Bourguet, William

    2013-01-01

    Multicellular organisms require specific intercellular communication to properly organize the complex body plan during embryogenesis and maintain its properties and functions during the entire life. While growth factors, neurotransmitters, and peptide hormones bind to membrane receptors, thereby inducing the activity of intracellular kinase cascades or the JAK-STAT signaling pathways, other small signaling compounds such as steroid hormones, certain vitamins, and metabolic intermediates enter, or are generated, within the target cells and bind to members of a large family of nuclear receptors (NRs). NRs are ligand-inducible transcription factors that control a plethora of biological phenomena, thus orchestrating complex events like development, organ homeostasis, immune function, and reproduction. NR-NR interactions are of major importance in these regulatory processes, as NRs regulate their target genes by binding to cognate DNA response elements essentially as homo- or heterodimers. A number of structural and functional studies have provided significant insights as to how combinatorial NRs rely on protein-protein contacts that discriminate geometric features of their DNA response elements, thereby allowing both binding site diversity and physiological specificity. Here, we will review our current understanding of NR-NR interactions and provide protocols for a number of experimental approaches that are useful for their study. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Receptor studies in biological psychiatry

    International Nuclear Information System (INIS)

    Fujiwara, Yutaka

    1992-01-01

    Recent advances in the pharmacological treatment of endogenous psychosis have led to the development of biological studies in psychiatry. Studies on neurotransmitter receptors were reviewed in order to apply positron-emission tomograph (PET) for biological psychiatry. The dopamine (DA) hypothesis for schizophrenia was advanced on the basis of the observed effects of neuroleptics and methamphetamine, and DA(D 2 ) receptor supersensitivity measured by PET and receptor binding in the schizophrenic brain. The clinical potencies of neuroleptics for schizophrenia were correlated with their abilities to inhibit the D 2 receptor, and not other receptors. The σ receptor was expected to be a site of antipsychotic action. However, the potency of drugs action on it was not correlated with clinical efficacy. Haloperidol binds with high affinity to the σ receptor, which may mediate acute dystonia, an extrapyramidal side effect of neuroleptics. Behavioral and neurochemical changes induced by methamphetamine treatment were studied as an animal model of schizophrenia, and both a decrease of D 2 receptor density and an increase of DA release were detected. The monoamine hypothesis for manic-depressive psychosis was advanced on the basis of the effect of reserpine, monoamine oxidase inhibitor and antidepressants. 3 H-clonidine binding sites were increased in platelet membranes of depressive patients, 3 H-imipramine binding sites were decreased. The GABA A receptor is the target site for the action of anxiolytics and antiepileptics such as benzodiazepines and barbiturates. Recent developments in molecular biology techniques have revealed the structure of receptor proteins, which are classified into two receptor families, the G-protein coupled type (D 2 ) and the ion-channel type (GABA A ). (J.P.N.)

  1. Possible Relevance of Receptor-Receptor Interactions between Viral- and Host-Coded Receptors for Viral-Induced Disease

    Directory of Open Access Journals (Sweden)

    Luigi F. Agnati

    2007-01-01

    Full Text Available It has been demonstrated that some viruses, such as the cytomegalovirus, code for G-protein coupled receptors not only to elude the immune system, but also to redirect cellular signaling in the receptor networks of the host cells. In view of the existence of receptor-receptor interactions, the hypothesis is introduced that these viral-coded receptors not only operate as constitutively active monomers, but also can affect other receptor function by interacting with receptors of the host cell. Furthermore, it is suggested that viruses could also insert not single receptors (monomers, but clusters of receptors (receptor mosaics, altering the cell metabolism in a profound way. The prevention of viral receptor-induced changes in host receptor networks may give rise to novel antiviral drugs that counteract viral-induced disease.

  2. Overweight and obesity in 4-5-year-old children in New Zealand: results from the first 4 years (2009-2012) of the B4School Check programme.

    Science.gov (United States)

    Rajput, Nitin; Tuohy, Pat; Mishra, Suryaprakash; Smith, Ash; Taylor, Barry

    2015-03-01

    We describe the prevalence of overweight and obesity in four-year-old children in New Zealand, variations with ethnicity and socio-economic status, and changes over the study duration using body mass index (BMI) measurements collected as part of the B4School Check programme. Demographic and BMI data were extracted for all children measured between 2009 and 2012. Overweight and obesity rates were estimated using International Obesity Task Force (IOTF) 2012 standards and the 85th (overweight) and 95th (obese) percentiles for BMI-for-age of the World Health Organization (WHO) 2006, Centers for Disease Control and Prevention 2000 and UK 1990 reference standards. A total of 168,744 BMI measurements were included in the analysis with a coverage rate of 66.5%. Mean BMI was 16.30 kg/m(2) in girls and 16.44 kg/m(2) in boys. Mean BMI z-score (WHO 2006 standards) was 0.601 in girls and 0.785 in boys. Using WHO 2006 standards, 16.9% of girls and 19.6% of boys were overweight and 13.8% of girls and 18.7% of boys were obese. Using IOTF standards, 18.3% of girls and 16.2% of boys were overweight and 5.7% of girls and 4.7% of boys were found obese. Prevalence of overweight and obesity was higher in Pacific and Maori children and those living in more socio-economically deprived areas than other children. No definite time-trends were observed over the study duration. The study reaffirms the high prevalence of overweight and obesity in pre-school children in New Zealand, and demonstrates the variations in prevalence when using different reference standards. © 2014 The Authors. Journal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

  3. Variation of the Side Chain Branch Position Leads to Vastly Improved Molecular Weight and OPV Performance in 4,8-dialkoxybenzo[1,2-b:4,5-b′]dithiophene/2,1,3-benzothiadiazole Copolymers

    Directory of Open Access Journals (Sweden)

    Robert C. Coffin

    2011-01-01

    Full Text Available Through manipulation of the solubilizing side chains, we were able to dramatically improve the molecular weight (Mw of 4,8-dialkoxybenzo[1,2-b:4,5-b′]dithiophene (BDT/2,1,3-benzothiadiazole (BT copolymers. When dodecyl side chains (P1 are employed at the 4- and 8-positions of the BDT unit, we obtain a chloroform-soluble copolymer fraction with Mw of 6.3 kg/mol. Surprisingly, by moving to the commonly employed 2-ethylhexyl branch (P2, Mw decreases to 3.4 kg/mol. This is despite numerous reports that this side chain increases solubility and Mw. By moving the ethyl branch in one position relative to the polymer backbone (1-ethylhexyl, P3, Mw is dramatically increased to 68.8 kg/mol. As a result of this Mw increase, the shape of the absorption profile is dramatically altered, with λmax = 637 nm compared with 598 nm for P1 and 579 nm for P2. The hole mobility as determined by thin film transistor (TFT measurements is improved from ~1×10−6 cm2/Vs for P1 and P2 to 7×10−4 cm2/Vs for P3, while solar cell power conversion efficiency in increased to 2.91% for P3 relative to 0.31% and 0.19% for P1 and P2, respectively.

  4. Peptide Receptor Radionuclide Therapy & Oncology

    NARCIS (Netherlands)

    H. Bergsma (Hendrik)

    2017-01-01

    markdownabstractNeuroendocrine tumors (NETs) are rare neoplasms with differences in clinical presentation, course and prognosis. Most of the NETs express the somatostatine receptor, which can be utilized for imaging and therapy. Radiolabeled somatostatin analogs can be used for peptide receptor

  5. Hydrocarbon Receptor Pathway in Dogs

    NARCIS (Netherlands)

    Steenbeek, F.G. van; Spee, B.; Penning, L.C.; Kummeling, A.; Gils, I.H.M.; Grinwis, G.C.M.; Leenen, D. van; Holstege, F.C.P.; Vos-Loohuis, M.; Rothuizen, J.; Leegwater, P.A.J.

    The aryl hydrocarbon receptor (AHR) mediates biological responses to toxic chemicals. An unexpected role for AHR in vascularization was suggested when mice lacking AHR displayed impaired closure of the ductus venosus after birth, as did knockout mice for aryl hydrocarbon receptor interacting

  6. Coronavirus spike-receptor interactions

    NARCIS (Netherlands)

    Mou, H.

    2015-01-01

    Coronaviruses cause important diseases in humans and animals. Coronavirus infection starts with the virus binding with its spike proteins to molecules present on the surface of host cells that act as receptors. This spike-receptor interaction is highly specific and determines the virus’ cell, tissue

  7. Neurobeachin regulates neurotransmitter receptor trafficking to synapses

    NARCIS (Netherlands)

    Nair, R.; Lauks, J.; Jung, S; Cooke, N.E.; de Wit, H.; Brose, N.; Kilimann, M.W.; Verhage, M.; Rhee, J.

    2013-01-01

    The surface density of neurotransmitter receptors at synapses is a key determinant of synaptic efficacy. Synaptic receptor accumulation is regulated by the transport, postsynaptic anchoring, and turnover of receptors, involving multiple trafficking, sorting, motor, and scaffold proteins. We found

  8. Probing Biased Signaling in Chemokine Receptors

    DEFF Research Database (Denmark)

    Amarandi, Roxana Maria; Hjortø, Gertrud Malene; Rosenkilde, Mette Marie

    2016-01-01

    The chemokine system mediates leukocyte migration during homeostatic and inflammatory processes. Traditionally, it is described as redundant and promiscuous, with a single chemokine ligand binding to different receptors and a single receptor having several ligands. Signaling of chemokine receptor...

  9. Dopamine Receptors and Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Shin Hisahara

    2011-01-01

    Full Text Available Parkinson's disease (PD is a progressive extrapyramidal motor disorder. Pathologically, this disease is characterized by the selective dopaminergic (DAergic neuronal degeneration in the substantia nigra. Correcting the DA deficiency in PD with levodopa (L-dopa significantly attenuates the motor symptoms; however, its effectiveness often declines, and L-dopa-related adverse effects emerge after long-term treatment. Nowadays, DA receptor agonists are useful medication even regarded as first choice to delay the starting of L-dopa therapy. In advanced stage of PD, they are also used as adjunct therapy together with L-dopa. DA receptor agonists act by stimulation of presynaptic and postsynaptic DA receptors. Despite the usefulness, they could be causative drugs for valvulopathy and nonmotor complication such as DA dysregulation syndrome (DDS. In this paper, physiological characteristics of DA receptor familyare discussed. We also discuss the validity, benefits, and specific adverse effects of pharmaceutical DA receptor agonist.

  10. Ryanodine receptor channelopathies

    Science.gov (United States)

    Betzenhauser, Matthew J.

    2010-01-01

    Ryanodine receptors (RyR) are intracellular Ca2+-permeable channels that provide the sarcoplasmic reticulum Ca2+ release required for skeletal and cardiac muscle contractions. RyR1 underlies skeletal muscle contraction, and RyR2 fulfills this role in cardiac muscle. Over the past 20 years, numerous mutations in both RyR isoforms have been identified and linked to skeletal and cardiac diseases. Malignant hyperthermia, central core disease, and catecholaminergic polymorphic ventricular tachycardia have been genetically linked to mutations in either RyR1 or RyR2. Thus, RyR channelopathies are both of interest because they cause significant human diseases and provide model systems that can be studied to elucidate important structure–function relationships of these ion channels. PMID:20179962

  11. Molecular characterization of opioid receptors

    Energy Technology Data Exchange (ETDEWEB)

    Howard, A.D.

    1986-01-01

    The aim of this research was to purify and characterize active opioid receptors and elucidate molecular aspects of opioid receptor heterogeneity. Purification to apparent homogeneity of an opioid binding protein from bovine caudate was achieved by solubilization in the non-ionic detergent, digitonin, followed by sequential chromatography on the opiate affinity matrix, ..beta..-naltrexylethylenediamine-CH-Sepharose 4B, and on the lectine affinity matrix, wheat germ agglutinin-agarose. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS-PAGE) followed by autoradiography revealed that radioiodinated purified receptor gave a single band. Purified receptor preparations showed a specific activity of 12,000-15,000 fmol of opiate bound per mg of protein. Radioiodinated human beta-endorphin (/sup 125/I-beta-end/sub H/) was used as a probe to investigate the ligand binding subunits of mu and delta opioid receptors. /sup 125/I-beta-end/sub H/ was shown to bind to a variety of opioid receptor-containing tissues with high affinity and specificity with preference for mu and delta sites, and with little, if any, binding to kappa sites. Affinity crosslinking techniques were employed to covalently link /sup 125/I-beta-end/sub H/ to opioid receptors, utilizing derivatives of bis-succinimidyl esters that are bifunctional crosslinkers with specificities for amino and sulfhydryl groups. This, and competition experiments with high type-selective ligands, permitted the assignment of two labeled peptides to their receptor types, namely a peptide of M/sub r/ = 65,000 for mu receptors and one of M/sub r/ = 53,000 for delta receptors.

  12. Estrogen-related receptor β (ERRβ) - renaissance receptor or receptor renaissance?

    Science.gov (United States)

    Divekar, Shailaja D; Tiek, Deanna M; Fernandez, Aileen; Riggins, Rebecca B

    2016-01-01

    Estrogen-related receptors (ERRs) are founding members of the orphan nuclear receptor (ONR) subgroup of the nuclear receptor superfamily. Twenty-seven years of study have yet to identify cognate ligands for the ERRs, though they have firmly placed ERRα and ERRγ at the intersection of cellular metabolism and oncogenesis. The pace of discovery for novel functions of ERRβ, however, has until recently been somewhat slower than that of its family members. ERRβ has also been largely ignored in summaries and perspectives of the ONR literature. Here, we provide an overview of established and emerging knowledge of ERRβ in mouse, man, and other species, highlighting unique aspects of ERRβ biology that set it apart from the other two estrogen-related receptors, with a focus on the impact of alternative splicing on the structure and function of this receptor.

  13. Corticosteroids decrease glomerular angiotensin receptors

    Energy Technology Data Exchange (ETDEWEB)

    Douglas, J.G.

    1987-03-01

    Angiotensin II (ANG II) receptors of glomerular mesangial cells are regulated in vivo by changes in Na balance, effects that are presumed to be secondary to changes in circulating ANG II. However, since changes in ANG II were accompanied by parallel changes in plasma aldosterone in all models tested, it is possible that aldosterone may have also participated in the modulation of glomerular ANG II receptors. To test this hypothesis, short-term aldosterone infusions within the physiological range were employed to favor actions that would be mediated through a high-affinity mineralocorticoid receptor. The glucocorticoid, dexamethasone, was also tested to determine the mineralocorticoid specificity of the response. Two infusion rates were associated with a decrease in glomerular /sup 125/I ANG II receptor density of 33 and 45%, respectively. Serum potassium and urinary Na/K ratio were lower in the aldosterone group. Spironolactone abolished the effect of aldosterone consistent with an action mediated through a specific mineralocorticoid receptor. These studies support the hypothesis that corticosteroids modulate glomerular ANG II receptors and validate the complexity of glomerular receptor modulation. The downregulation observed would be expected to diminish the ability of ANG II to influence glomerular hemodynamics in models such as mineralocorticoid and glucocorticoid-induced hypertension.

  14. Radioiodinated ligands for dopamine receptors

    International Nuclear Information System (INIS)

    Kung, H.F.

    1994-01-01

    The dopamine receptor system is important for normal brain function; it is also the apparent action site for various neuroleptic drugs for the treatment of schizophrenia and other metal disorders. In the past few years radioiodinated ligands for single photon emission tomography (SPECT) have been successfully developed and tested in humans: [ 123 I]TISCH for D1 dopamine receptors; [ 123 I]IBZM, epidepride, IBF and FIDA2, four iodobenzamide derivatives, for D2/D3 dopamine receptors. In addition, [ 123 I]β-CIT (RTI-55) and IPT, cocaine derivatives, for the dopamine reuptake site are potentially useful for diagnosis of loss of dopamine neurons. The first iodinated ligand, (R)trans-7-OH-PIPAT, for D3 dopamine receptors, was synthesized and characterized with cloned cell lines (Spodoptera frugiperda, Sf9) expressing the D2 and D3 dopamine receptors and with rat basal forebrain membrane preparations. Most of the known iodobenzamides displayed similar potency in binding to both D2 and D3 dopamine receptors expressed in the cell lines. Initial studies appear to suggest that by fine tuning the structures it may be possible to develop agents specific for D2 and D3 dopamine receptors. It is important to investigate D2/D3 selectivity for this series of potent ligands

  15. Lysophospholipid receptors in drug discovery.

    Science.gov (United States)

    Kihara, Yasuyuki; Mizuno, Hirotaka; Chun, Jerold

    2015-05-01

    Lysophospholipids (LPs), including lysophosphatidic acid (LPA), sphingosine 1-phospate (S1P), lysophosphatidylinositol (LPI), and lysophosphatidylserine (LysoPS), are bioactive lipids that transduce signals through their specific cell-surface G protein-coupled receptors, LPA1-6, S1P1-5, LPI1, and LysoPS1-3, respectively. These LPs and their receptors have been implicated in both physiological and pathophysiological processes such as autoimmune diseases, neurodegenerative diseases, fibrosis, pain, cancer, inflammation, metabolic syndrome, bone formation, fertility, organismal development, and other effects on most organ systems. Advances in the LP receptor field have enabled the development of novel small molecules targeting LP receptors for several diseases. Most notably, fingolimod (FTY720, Gilenya, Novartis), an S1P receptor modulator, became the first FDA-approved medicine as an orally bioavailable drug for treating relapsing forms of multiple sclerosis. This success is currently being followed by multiple, mechanistically related compounds targeting S1P receptor subtypes, which are in various stages of clinical development. In addition, an LPA1 antagonist, BMS-986020 (Bristol-Myers Squibb), is in Phase 2 clinical development for treating idiopathic pulmonary fibrosis, as a distinct compound, SAR100842 (Sanofi) for the treatment of systemic sclerosis and related fibrotic diseases. This review summarizes the current state of drug discovery in the LP receptor field. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. A transient receptor potential channel expressed in taste receptor cells.

    Science.gov (United States)

    Pérez, Cristian A; Huang, Liquan; Rong, Minqing; Kozak, J Ashot; Preuss, Axel K; Zhang, Hailin; Max, Marianna; Margolskee, Robert F

    2002-11-01

    We used differential screening of cDNAs from individual taste receptor cells to identify candidate taste transduction elements in mice. Among the differentially expressed clones, one encoded Trpm5, a member of the mammalian family of transient receptor potential (TRP) channels. We found Trpm5 to be expressed in a restricted manner, with particularly high levels in taste tissue. In taste cells, Trpm5 was coexpressed with taste-signaling molecules such as alpha-gustducin, Ggamma13, phospholipase C-beta2 (PLC-beta2) and inositol 1,4,5-trisphosphate receptor type III (IP3R3). Our heterologous expression studies of Trpm5 indicate that it functions as a cationic channel that is gated when internal calcium stores are depleted. Trpm5 may be responsible for capacitative calcium entry in taste receptor cells that respond to bitter and/or sweet compounds.

  17. Quantitative receptor radioautography in the study of receptor-receptor interactions in the nucleus tractus solitarii

    Directory of Open Access Journals (Sweden)

    Fior-Chadi D.R.

    1998-01-01

    Full Text Available The nucleus tractus solitarii (NTS in the dorsomedial medulla comprises a wide range of neuropeptides and biogenic amines. Several of them are related to mechanisms of central blood pressure control. Angiotensin II (Ang II, neuropeptide Y (NPY and noradrenaline (NA are found in the NTS cells, as well as their receptors. Based on this observation we have evaluated the modulatory effect of these peptide receptors on a2-adrenoceptors in the NTS. Using quantitative receptor radioautography, we observed that NPY and Ang II receptors decreased the affinity of a2-adrenoceptors for their agonists in the NTS of the rat. Cardiovascular experiments agreed with the in vitro data. Coinjection of a threshold dose of Ang II or of the NPY agonists together with an ED50 dose of adrenergic agonists such as NA, adrenaline and clonidine counteracted the depressor effect produced by the a2-agonist in the NTS. The results provide evidence for the existence of an antagonistic interaction between Ang II at1 receptors and NPY receptor subtypes with the a2-adrenoceptors in the NTS. This receptor interaction may reduce the transduction over the a2-adrenoceptors which can be important in central cardiovascular regulation and in the development of hypertension

  18. Glutamate receptor ligands

    DEFF Research Database (Denmark)

    Guldbrandt, Mette; Johansen, Tommy N; Frydenvang, Karla Andrea

    2002-01-01

    Homologation and substitution on the carbon backbone of (S)-glutamic acid [(S)-Glu, 1], as well as absolute stereochemistry, are structural parameters of key importance for the pharmacological profile of (S)-Glu receptor ligands. We describe a series of methyl-substituted 2-aminoadipic acid (AA...... or slightly lower potencies than (S)-AA [e.g., EC(50) = 76 microM for (2S,4S)-4-methyl-AA (5a) as compared to EC(50) = 35 microM for (S)-AA]. The position of the methyl substituent had a profound effect on the observed pharmacology, whereas the absolute stereochemistry at the methylated carbon atom had a very......) analogs, and the synthesis, stereochemistry, and enantiopharmacology of 3-methyl-AA (4a-d), 4-methyl-AA (5a-d), 5-methyl-AA (6a-d), and (E)-Delta(4)-5-methyl-AA (7a and 7b) are reported. The compounds were resolved using chiral HPLC and the configurational assignments of the enantiomers were based on X...

  19. Nuclear Receptor Signaling Atlas (NURSA)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Nuclear Receptor Signaling Atlas (NURSA) is designed to foster the development of a comprehensive understanding of the structure, function, and role in disease...

  20. L-glutamate Receptor In Paramecium

    Science.gov (United States)

    Bernal-Martínez, Juan; Ortega-Soto, Arturo

    2004-09-01

    Behavioral, electrophysiological and biochemical experiments were performed in order to establish the presence of a glutamate receptor in the ciliate Paramecium. It was found that an AMPA/KA receptor is functionally expressed in Paramecium and that this receptor is immunologically and fillogenetically related to the AMPA/KA receptor present in vertebrates.

  1. Receptor-targeted metalloradiopharmaceuticals. Final technical report

    International Nuclear Information System (INIS)

    Green, Mark A.

    2000-01-01

    Copper (II) and platinum (II) coordination complexes were prepared and characterized. These complexes were designed to afford structural homology with steroidal and non-steroidal estrogens for possible use as receptor-targeted radiopharmaceuticals. While weak affinity for the estrogen receptor was detectable, none would appear to have sufficient receptor-affinity for estrogen-receptor-targeted imaging or therapy

  2. [The receptor theory of atherosclerosis].

    Science.gov (United States)

    Likhoded, V G; Bondarenko, V M; Gintsburg, A L

    2010-01-01

    Lipopolysaccharides of Gram-negative bacteria can interact with Toll-like receptor 4 (TLR4) and induce atheroma formation. The risk of atherosclerosis is decreased in case of TLR4 mutation. Other bacterial ligands and endogenous ligands of TLRs can also be involved in induction of atherogenesis. The general concept of atherosclerosis pathogentsis is presented. According to this concept atherogenesis can be initiated by some reactions resulting from interaction of exogenous and endogenous microbial ligands with Toll-like receptors.

  3. Natural product HTP screening for antibacterial (E.coli 0157:H7) and anti-inflammatory agents in (LPS from E. coli O111:B4) activated macrophages and microglial cells; focus on sepsis.

    Science.gov (United States)

    Mazzio, Elizabeth A; Li, Nan; Bauer, David; Mendonca, Patricia; Taka, Equar; Darb, Mohammed; Thomas, Leeshawn; Williams, Henry; Soliman, Karam F A

    2016-11-15

    Acute systemic inflammatory response syndrome arising from infection can lead to multiple organ failure and death, with greater susceptibility occurring in immunocompromised individuals. Moreover, sub-acute chronic inflammation is a contributor to the pathology of diverse degenerative diseases (Parkinson's disease, Alzheimer's disease and arthritis). Given the known limitations in Western medicine to treat a broad range of inflammatory related illness as well as the emergence of antibiotic resistance, there is a renewed interest in complementary and alternative medicines (CAMs) to achieve these means. A high throughput (HTP) screening of >1400 commonly sold natural products (bulk herbs, cooking spices, teas, leaves, supplement components, nutraceutical food components, fruit and vegetables, rinds, seeds, polyphenolics etc.) was conducted to elucidate anti-inflammatory substances in lipopolysaccharide (LPS) (E. coli serotype O111:B4) monocytes: RAW 264.7 macrophages [peripheral], BV-2 microglia [brain]) relative to hydrocortisone, dexamethasone and L-N6-(1Iminoethyl)lysine (L-NIL). HTP evaluation was also carried out for lethal kill curves against E.coli 0157:H7 1x10 6 CFU/mL relative to penicillin. Validation studies were performed to assess cytokine profiling using antibody arrays. Findings were corroborated by independent ELISAs and NO2-/iNOS expression quantified using the Griess Reagent and immunocytochemistry, respectively. For robust screening, we developed an in-vitro efficacy paradigm to ensure anti-inflammatory parameters were observed independent of cytotoxicity. This caution was taken given that many plants exert tumoricidal and anti-inflammatory effects at close range through similar signaling pathways, which could lead to false positives. The data show that activated BV-2 microglia cells (+ LPS 1μg/ml) release >10-fold greater IL-6, MIP1/2, RANTES and nitric oxide (NO2-), where RAW 264.7 macrophages (+ LPS 1μg/ml) produced > 10-fold rise in sTNFR2

  4. Odorant Receptor Desensitization in Insects

    Directory of Open Access Journals (Sweden)

    Hao Guo

    2017-12-01

    Full Text Available Insects and other arthropods transmit devastating human diseases, and these vectors use chemical senses to target humans. Understanding how these animals detect, respond, and adapt to volatile odorants may lead to novel ways to disrupt host localization or mate recognition in these pests. The past decade has led to remarkable progress in understanding odorant detection in arthropods. Insects use odorant-gated ion channels, first discovered in Drosophila melanogaster , to detect volatile chemicals. In flies, 60 “tuning” receptor subunits combine with a common subunit, Orco ( o dorant r eceptor co receptor to form ligand-gated ion channels. The mechanisms underlying odorant receptor desensitization in insects are largely unknown. Recent work reveals that dephosphorylation of serine 289 on the shared Orco subunit is responsible for slow, odor-induced receptor desensitization. Dephosphorylation has no effect on the localization of the receptor protein, and activation of the olfactory neurons in the absence of odor is sufficient to induce dephosphorylation and desensitization. These findings reveal a major component of receptor modulation in this important group of disease vectors, and implicate a second messenger feedback mechanism in this process.

  5. Nuclear Receptors, RXR, and the Big Bang.

    Science.gov (United States)

    Evans, Ronald M; Mangelsdorf, David J

    2014-03-27

    Isolation of genes encoding the receptors for steroids, retinoids, vitamin D, and thyroid hormone and their structural and functional analysis revealed an evolutionarily conserved template for nuclear hormone receptors. This discovery sparked identification of numerous genes encoding related proteins, termed orphan receptors. Characterization of these orphan receptors and, in particular, of the retinoid X receptor (RXR) positioned nuclear receptors at the epicenter of the "Big Bang" of molecular endocrinology. This Review provides a personal perspective on nuclear receptors and explores their integrated and coordinated signaling networks that are essential for multicellular life, highlighting the RXR heterodimer and its associated ligands and transcriptional mechanism. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Expression of GABAergic receptors in mouse taste receptor cells.

    Directory of Open Access Journals (Sweden)

    Margaret R Starostik

    Full Text Available BACKGROUND: Multiple excitatory neurotransmitters have been identified in the mammalian taste transduction, with few studies focused on inhibitory neurotransmitters. Since the synthetic enzyme glutamate decarboxylase (GAD for gamma-aminobutyric acid (GABA is expressed in a subset of mouse taste cells, we hypothesized that other components of the GABA signaling pathway are likely expressed in this system. GABA signaling is initiated by the activation of either ionotropic receptors (GABA(A and GABA(C or metabotropic receptors (GABA(B while it is terminated by the re-uptake of GABA through transporters (GATs. METHODOLOGY/PRINCIPAL FINDINGS: Using reverse transcriptase-PCR (RT-PCR analysis, we investigated the expression of different GABA signaling molecules in the mouse taste system. Taste receptor cells (TRCs in the circumvallate papillae express multiple subunits of the GABA(A and GABA(B receptors as well as multiple GATs. Immunocytochemical analyses examined the distribution of the GABA machinery in the circumvallate papillae. Both GABA(A-and GABA(B- immunoreactivity were detected in the peripheral taste receptor cells. We also used transgenic mice that express green fluorescent protein (GFP in either the Type II taste cells, which can respond to bitter, sweet or umami taste stimuli, or in the Type III GAD67 expressing taste cells. Thus, we were able to identify that GABAergic receptors are expressed in some Type II and Type III taste cells. Mouse GAT4 labeling was concentrated in the cells surrounding the taste buds with a few positively labeled TRCs at the margins of the taste buds. CONCLUSIONS/SIGNIFICANCE: The presence of GABAergic receptors localized on Type II and Type III taste cells suggests that GABA is likely modulating evoked taste responses in the mouse taste bud.

  7. Toll-like receptors in neonatal sepsis.

    LENUS (Irish Health Repository)

    O'Hare, Fiona M

    2013-06-01

    Toll-like receptors are vital transmembrane receptors that initiate the innate immune response to many micro-organisms. The discovery of these receptors has improved our understanding of host-pathogen interactions, and these receptors play an important role in the pathogenesis of multiple neonatal conditions such as sepsis and brain injury. Toll-like receptors, especially TLRs 2 and 4, are associated with necrotizing enterocolitis, periventricular leukomalacia and sepsis.

  8. NMDA receptor signaling: death or survival?

    OpenAIRE

    LUO, Tong; WU, Wei-Hua; CHEN, Bo-Shiun

    2011-01-01

    Glutamate-induced neuronal damage is mainly caused by overactivation of N-methyl-D-aspartate (NMDA) receptors. Conversely, normal physiological brain function and neuronal survival require adequate activation of NMDA receptors. Studies have revealed that NMDA receptor-induced neuronal death or survival is mediated through distinct subset of NMDA receptors triggering different intracellular signaling pathways. Here we discuss recent advances in the characterization of NMDA receptors in neurona...

  9. Regulation of NMDA Receptors by Phosphorylation

    OpenAIRE

    Chen, Bo-Shiun; Roche, Katherine W.

    2007-01-01

    N-methyl-D-aspartate (NMDA) receptors are critical for neuronal development and synaptic plasticity. The molecular mechanisms underlying the synaptic localization and functional regulation of NMDA receptors have been the subject of extensive studies. In particular, phosphorylation has emerged as a fundamental mechanism that regulates NMDA receptor trafficking and can alter the channel properties of NMDA receptors. Here we summarize recent advances in the characterization of NMDA receptor phos...

  10. Studies on insulin receptor, 2

    International Nuclear Information System (INIS)

    Sakai, Yukio

    1979-01-01

    The present study is to investigate an influence of starvation and high fat diet on insulin receptor of the plasma membrane by means of radioreceptor assay using 125 I-labelled insulin. Male guinea pigs of Hartley strain were employed for the starvation study, and 125 I-insulin binding capacity on the plasma membrane of the liver and kidney was determined at 24, 48 and 72 hours of the fast after the last meal. Male rats of Wistar strain were employed for the high fat study where the diet containing 35% of butter was fed ad libitum for 38 or 68 days. The animals were killed at the fast of 12 hours, and 125 I-insulin binding capacity on the plasma membrane of the liver was determined. The results obtained are summarized as follows: 1) An increase in 125 I-insulin binding capacity on the plasma membrane of the liver and kidney was observed by the starvation for 24 to 72 hours. 2) The mechanism of the increase by starvation was considered to be different by the organs; it was due to an increase in number of insulin receptor in the liver, and due to an increase in affinity of insulin receptor in the kidney. 3) In non-obese rats fed with high fat diet, the number of insulin receptor on the liver plasma membrane showed a decrease, and this observation clearly indicated that the decrease in number of the receptor did not depend on the obesity. 4) Obese rats also fed with high fat diet presented a decrease in number of insulin receptor without an elevation of insulin levels in the circulating blood. This indicated that at least in the obese rats fed with high fat diet, the decrease in number of the receptor was not due to hyperinsulinemia. (author)

  11. Pyronaridine-artesunate or dihydroartemisinin-piperaquine versus current first-line therapies for repeated treatment of uncomplicated malaria: a randomised, multicentre, open-label, longitudinal, controlled, phase 3b/4 trial.

    Science.gov (United States)

    2018-04-07

    Artemether-lumefantrine and artesunate-amodiaquine are used as first-line artemisinin-based combination therapies (ACTs) in west Africa. Pyronaridine-artesunate and dihydroartemisinin-piperaquine are potentially useful for diversification of ACTs in this region, but further safety and efficacy data are required on malaria retreatment. We did a randomised, multicentre, open-label, longitudinal, controlled phase 3b/4 clinical trial at seven tertiary centres in Burkina Faso, Guinea, and Mali. Eligible participants for first malaria episode and all retreatment episodes were adults and children aged 6 months and older with microscopically confirmed Plasmodium spp malaria (>0 to PCR-adjusted for Plasmodium falciparum and unadjusted for other Plasmodium spp) in the per-protocol population on days 28 and 42 (non-inferiority margin 5%). Safety was assessed in all participants who received one dose of study drug. This study is registered at the Pan African Clinical Trials Registry (PACTR201105000286876). Between Oct 24, 2011, and Feb 1, 2016, we assigned 4710 eligible participants to the different treatment strategies: 1342 to pyronaridine-artesunate, 967 to artemether-lumefantrine, 1061 to artesunate-amodiaquine, and 1340 to dihydroartemisinin-piperaquine. The 2-year malaria incidence rate in the ITT population was non-inferior for pyronaridine-artesunate versus artemether-lumefantrine (1·77, 95% CI 1·63-1·93 vs 1·87, 1·72-2·03; rate ratio [RR] 1·05, 95% CI 0·94-1·17); and versus artesunate-amodiaquine (1·39, 95% CI 1·22-1·59 vs 1·35, 1·18-1·54; RR 0·97, 0·87-1·07). Similarly, this endpoint was non-inferior for dihydroartemisinin-piperaquine versus artemether-lumefantrine (1·16, 95% CI 1·01-1·34 vs 1·42 1·25-1·62; RR 1·22, 95% CI 1·06-1·41) and versus artesunate-amodiaquine (1·35, 1·21-1·51 vs 1·68, 1·51-1·88; RR 1·25, 1·02-1·50). For uncomplicated P falciparum malaria, PCR-adjusted ACPR was greater than 99·5% at day 28 and greater than

  12. Effects of nuclear receptor transactivation on steroid hormone synthesis and gene expression in porcine Leydig cells.

    Science.gov (United States)

    Gray, Matthew A; Squires, E James

    2013-01-01

    Male pigs are routinely castrated at a young age to prevent the formation of androstenone, a 16-androstene testicular steroid that is a major component of boar taint. The practice of castration has been increasingly viewed as unfavorable, due to both economic considerations and animal welfare concerns. Other means of controlling boar taint, including reducing the synthesis of androstenone in the testes, would eliminate the need for castration. In this study, we determined the effects of transactivation of three nuclear receptors, the constitutive androstane receptor (CAR), pregnane X receptor (PXR), and farnesoid X receptor (FXR), on gene expression and steroid hormone metabolism in primary porcine Leydig cells. Primary cells were isolated from mature boars, and transcript expression levels were assayed using real-time PCR. The transcripts of interest included porcine orthologs of common phase I and phase II metabolic enzymes, enzymes involved in steroidogenesis, and transcripts previously shown to be differentially expressed in boars with high androstenone and boar taint levels. Transactivation of CAR, PXR, or FXR increased the expression of several genes involved in steroidogenesis, including cytochrome B5A (CYB5A) and cytochrome B5 reductase 1 (CYB5R1), as well as hydroxysteroid (17-beta) dehydrogenase 4 (HSD17B4) and retinol dehydrogenase 12 (RDH12). Treatment with (6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde-O-(3,4-dichlorobenzyl)oxime (CITCO), a CAR agonist, or rifampicin (RIF), a PXR agonist, resulted in significantly (pnuclear receptors may lead to increased levels of 16-androstene steroids, likely by altering the activity of CYP17A1 through CYB5A and CYB5R1 to the andien-β synthase reaction and away from the 17α-hydroxylase and C17, 20 lyase reactions. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Purinergic Receptors in Ocular Inflammation

    Directory of Open Access Journals (Sweden)

    Ana Guzman-Aranguez

    2014-01-01

    Full Text Available Inflammation is a complex process that implies the interaction between cells and molecular mediators, which, when not properly “tuned,” can lead to disease. When inflammation affects the eye, it can produce severe disorders affecting the superficial and internal parts of the visual organ. The nucleoside adenosine and nucleotides including adenine mononucleotides like ADP and ATP and dinucleotides such as P1,P4-diadenosine tetraphosphate (Ap4A, and P1,P5-diadenosine pentaphosphate (Ap5A are present in different ocular locations and therefore they may contribute/modulate inflammatory processes. Adenosine receptors, in particular A2A adenosine receptors, present anti-inflammatory action in acute and chronic retinal inflammation. Regarding the A3 receptor, selective agonists like N6-(3-iodobenzyl-5′-N-methylcarboxamidoadenosine (CF101 have been used for the treatment of inflammatory ophthalmic diseases such as dry eye and uveoretinitis. Sideways, diverse stimuli (sensory stimulation, large intraocular pressure increases can produce a release of ATP from ocular sensory innervation or after injury to ocular tissues. Then, ATP will activate purinergic P2 receptors present in sensory nerve endings, the iris, the ciliary body, or other tissues surrounding the anterior chamber of the eye to produce uveitis/endophthalmitis. In summary, adenosine and nucleotides can activate receptors in ocular structures susceptible to suffer from inflammatory processes. This involvement suggests the possible use of purinergic agonists and antagonists as therapeutic targets for ocular inflammation.

  14. Photo-antagonism of the GABAA receptor.

    Science.gov (United States)

    Mortensen, Martin; Iqbal, Favaad; Pandurangan, Arun P; Hannan, Saad; Huckvale, Rosemary; Topf, Maya; Baker, James R; Smart, Trevor G

    2014-07-29

    Neurotransmitter receptor trafficking is fundamentally important for synaptic transmission and neural network activity. GABAA receptors and inhibitory synapses are vital components of brain function, yet much of our knowledge regarding receptor mobility and function at inhibitory synapses is derived indirectly from using recombinant receptors, antibody-tagged native receptors and pharmacological treatments. Here we describe the use of a set of research tools that can irreversibly bind to and affect the function of recombinant and neuronal GABAA receptors following ultraviolet photoactivation. These compounds are based on the competitive antagonist gabazine and incorporate a variety of photoactive groups. By using site-directed mutagenesis and ligand-docking studies, they reveal new areas of the GABA binding site at the interface between receptor β and α subunits. These compounds enable the selected inactivation of native GABAA receptor populations providing new insight into the function of inhibitory synapses and extrasynaptic receptors in controlling neuronal excitation.

  15. Scavenger receptors in homeostasis and immunity.

    Science.gov (United States)

    Canton, Johnathan; Neculai, Dante; Grinstein, Sergio

    2013-09-01

    Scavenger receptors were originally identified by their ability to recognize and to remove modified lipoproteins; however, it is now appreciated that they carry out a striking range of functions, including pathogen clearance, lipid transport, the transport of cargo within the cell and even functioning as taste receptors. The large repertoire of ligands recognized by scavenger receptors and their broad range of functions are not only due to the wide range of receptors that constitute this family but also to their ability to partner with various co-receptors. The ability of individual scavenger receptors to associate with different co-receptors makes their responsiveness extremely versatile. This Review highlights recent insights into the structural features that determine the function of scavenger receptors and the emerging role that these receptors have in immune responses, notably in macrophage polarization and in the pathogenesis of diseases such as atherosclerosis and Alzheimer's disease.

  16. Identification and mechanism of ABA receptor antagonism

    Energy Technology Data Exchange (ETDEWEB)

    Melcher, Karsten; Xu, Yong; Ng, Ley-Moy; Zhou, X. Edward; Soon, Fen-Fen; Chinnusamy, Viswanathan; Suino-Powell, Kelly M; Kovach, Amanda; Tham, Fook S.; Cutler, Sean R.; Li, Jun; Yong, Eu-Leong; Zhu, Jian-Kang; Xu, H. Eric (NU Sinapore); (Van Andel); (UCR)

    2010-11-11

    The phytohormone abscisic acid (ABA) functions through a family of fourteen PYR/PYL receptors, which were identified by resistance to pyrabactin, a synthetic inhibitor of seed germination. ABA activates these receptors to inhibit type 2C protein phosphatases, such as ABI1, yet it remains unclear whether these receptors can be antagonized. Here we demonstrate that pyrabactin is an agonist of PYR1 and PYL1 but is unexpectedly an antagonist of PYL2. Crystal structures of the PYL2-pyrabactin and PYL1-pyrabactin-ABI1 complexes reveal the mechanism responsible for receptor-selective activation and inhibition, which enables us to design mutations that convert PYL1 to a pyrabactin-inhibited receptor and PYL2 to a pyrabactin-activated receptor and to identify new pyrabactin-based ABA receptor agonists. Together, our results establish a new concept of ABA receptor antagonism, illustrate its underlying mechanisms and provide a rational framework for discovering novel ABA receptor ligands.

  17. Modulation of Xenobiotic Receptors by Steroids

    Directory of Open Access Journals (Sweden)

    Delira Robbins

    2013-06-01

    Full Text Available Nuclear receptors (NRs are ligand-activated transcription factors that regulate the expression of their target genes. NRs play important roles in many human diseases, including metabolic diseases and cancer, and are therefore a key class of therapeutic targets. Steroids play important roles in regulating nuclear receptors; in addition to being ligands of steroid receptors, steroids (and their metabolites also regulate other NRs, such as the pregnane X receptor and constitutive androstane receptor (termed xenobiotic receptors, which participate in steroid metabolism. Xenobiotic receptors have promiscuous ligand-binding properties, and their structurally diverse ligands include steroids and their metabolites. Therefore, steroids, their metabolism and metabolites, xenobiotic receptors, steroid receptors, and the respective signaling pathways they regulate have functional interactions. This review discusses these functional interactions and their implications for activities mediated by steroid receptors and xenobiotic receptors, focusing on steroids that modulate pathways involving the pregnane X receptor and constitutive androstane receptor. The emphasis of the review is on structure-function studies of xenobiotic receptors bound to steroid ligands.

  18. 5-Hydroxytryptamine type 7 receptor neuroprotection against NMDA-induced excitotoxicity is PDGFβ receptor dependent.

    Science.gov (United States)

    Vasefi, Maryam S; Kruk, Jeff S; Heikkila, John J; Beazely, Michael A

    2013-04-01

    The serotonin (5-HT) type 7 receptor is expressed throughout the CNS including the hippocampus. Long-term (2-24 h) activation of 5-HT7 receptors regulates growth factor receptor expression, including the expression of platelet-derived growth factor (PDGF) β receptors. Direct activation of PDGFβ receptors in primary hippocampal and cortical neurons inhibits NMDA receptor activity and attenuates NMDA receptor-induced neurotoxicity. Our objective was to investigate whether the 5-HT7 receptor-induced increase in PDGFβ receptor expression would be similarly neuroprotective. We demonstrate that 5-HT7 receptor agonist treatment in primary hippocampal neurons also increases the expression of phospholipase C (PLC) γ, a downstream effector of PDGFβ receptors associated with the inhibition of NMDA receptor activity. To determine if the up-regulation of PDGFβ receptors is neuroprotective, primary hippocampal neurons were incubated with the 5-HT7 receptor agonist, LP 12, for 24 h. Indeed, LP 12 treatment prevented NMDA-induced neurotoxicity and this effect was dependent on PDGFβ receptor kinase activity. Treatment of primary neurons with LP 12 also differentially altered NMDA receptor subunit expression, reducing the expression of NR1 and NR2B, but not NR2A. These findings demonstrate the potential for providing growth factor receptor-dependent neuroprotective effects using small-molecule ligands of G protein-coupled receptors. © 2013 International Society for Neurochemistry.

  19. Prolactin receptors in uterine leiomyomas

    International Nuclear Information System (INIS)

    Baban, Rayah S.; Farid, Yahya Y.; Al-Zuheiri, Shatha T.

    2008-01-01

    Objective was to identify the location of prolactin receptors in patientswith uterine leiomyomas and their host myometrium as well as normalmyometrium. A case control study was conducted at the College of MedicineAl-Nahrain University, Baghdad, Iraq during the period from 2004-2006. Thesamples were collected at Obstetrics and Gynecological Departments of 4hospitals in Baghdad City (Al-Khadimiya Teaching Hospital, Al-Noor,Al-Kharch, and Al-Sadoon Hospital). Sections from large and small tumors(n=53) with their host myometriums and from normal myometriums (n=40) werestained immunohistochemically for prolactin receptors. Prolactin receptorswere positively seen in all cases examined including patient and comparisontissues, in the form of dark brown staining. Staining was heterogeneous andvaried in intensity from one case to another and sometimes from one are toanother in the same section. The increase in prolactin receptors in leiomyomais expected given that the underlying host myometrium abnormal. (author)

  20. The 79,370-bp conjugative plasmid pB4 consists of an IncP-1beta backbone loaded with a chromate resistance transposon, the strA-strB streptomycin resistance gene pair, the oxacillinase gene bla(NPS-1), and a tripartite antibiotic efflux system of the resistance-nodulation-division family.

    Science.gov (United States)

    Tauch, A; Schlüter, A; Bischoff, N; Goesmann, A; Meyer, F; Pühler, A

    2003-02-01

    Plasmid pB4 is a conjugative antibiotic resistance plasmid, originally isolated from a microbial community growing in activated sludge, by means of an exogenous isolation method with Pseudomonas sp. B13 as recipient. We have determined the complete nucleotide sequence of pB4. The plasmid is 79,370 bp long and contains at least 81 complete coding regions. A suite of coding regions predicted to be involved in plasmid replication, plasmid maintenance, and conjugative transfer revealed significant similarity to the IncP-1beta backbone of R751. Four resistance gene regions comprising mobile genetic elements are inserted in the IncP-1beta backbone of pB4. The modular 'gene load' of pB4 includes (1) the novel transposon Tn 5719 containing genes characteristic of chromate resistance determinants, (2) the transposon Tn 5393c carrying the widespread streptomycin resistance gene pair strA-strB, (3) the beta-lactam antibiotic resistance gene bla(NPS-1) flanked by highly conserved sequences characteristic of integrons, and (4) a tripartite antibiotic resistance determinant comprising an efflux protein of the resistance-nodulation-division (RND) family, a periplasmic membrane fusion protein (MFP), and an outer membrane factor (OMF). The components of the RND-MFP-OMF efflux system showed the highest similarity to the products of the mexCD-oprJ determinant from the Pseudomonas aeruginosa chromosome. Functional analysis of the cloned resistance region from pB4 in Pseudomonas sp. B13 indicated that the RND-MFP-OMF efflux system conferred high-level resistance to erythromycin and roxithromycin resistance on the host strain. This is the first example of an RND-MFP-OMF-type antibiotic resistance determinant to be found in a plasmid genome. The global genetic organization of pB4 implies that its gene load might be disseminated between bacteria in different habitats by the combined action of the conjugation apparatus and the mobility of its component elements.

  1. Mechanism for the activation of glutamate receptors

    Science.gov (United States)

    Scientists at the NIH have used a technique called cryo-electron microscopy to determine a molecular mechanism for the activation and desensitization of ionotropic glutamate receptors, a prominent class of neurotransmitter receptors in the brain and spina

  2. Genetics Home Reference: leptin receptor deficiency

    Science.gov (United States)

    ... People with leptin receptor deficiency also have hypogonadotropic hypogonadism, which is a condition caused by reduced production ... weight gain associated with this disorder. Because hypogonadotropic hypogonadism occurs in leptin receptor deficiency , researchers suggest that ...

  3. Excitatory amino acid receptor antagonists

    DEFF Research Database (Denmark)

    Johansen, T N; Frydenvang, Karla Andrea; Ebert, B

    1997-01-01

    We have previously shown that (RS)-2-amino-2-(5-tert-butyl-3-hydroxyisoxazol-4-yl)acetic acid (ATAA) is an antagonist at N-methyl-D-aspartic acid (NMDA) and (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) receptors. We have now resolved ATAA via diastereomeric salt formation...

  4. Pharmacological approach of the receptors

    International Nuclear Information System (INIS)

    Puech, A.J.

    1989-01-01

    This paper explains the three main goals for clinical positron emission tomography (PET) studies: detection of receptor abnormalities in groups of patients to propose therapeutic indication of new ligands; validation of current hypothesis of drug effect; rational clinical drug development specially for dose-finding studies. (H.W.)

  5. Are olfactory receptors really olfactive?

    DEFF Research Database (Denmark)

    Giorgi, Franco; Maggio, Roberto; Bruni, Luis Emilio

    2011-01-01

    Any living organism interacts with and responds specifically to environmental molecules by expressing specific olfactory receptors. This specificity will be first examined in causal terms with particular emphasis on the mechanisms controlling olfactory gene expression, cell-to-cell interactions a...

  6. Cannabinoid receptor localization in brain

    Energy Technology Data Exchange (ETDEWEB)

    Herkenham, M.; Lynn, A.B.; Little, M.D.; Johnson, M.R.; Melvin, L.S.; de Costa, B.R.; Rice, K.C. (National Institute of Mental Health, Bethesda, MD (USA))

    1990-03-01

    (3H)CP 55,940, a radiolabeled synthetic cannabinoid, which is 10-100 times more potent in vivo than delta 9-tetrahydrocannabinol, was used to characterize and localize a specific cannabinoid receptor in brain sections. The potencies of a series of natural and synthetic cannabinoids as competitors of (3H)CP 55,940 binding correlated closely with their relative potencies in several biological assays, suggesting that the receptor characterized in our in vitro assay is the same receptor that mediates behavioral and pharmacological effects of cannabinoids, including human subjective experience. Autoradiography of cannabinoid receptors in brain sections from several mammalian species, including human, reveals a unique and conserved distribution; binding is most dense in outflow nuclei of the basal ganglia--the substantia nigra pars reticulata and globus pallidus--and in the hippocampus and cerebellum. Generally high densities in forebrain and cerebellum implicate roles for cannabinoids in cognition and movement. Sparse densities in lower brainstem areas controlling cardiovascular and respiratory functions may explain why high doses of delta 9-tetrahydrocannabinol are not lethal.

  7. Ligand-guided receptor optimization.

    Science.gov (United States)

    Katritch, Vsevolod; Rueda, Manuel; Abagyan, Ruben

    2012-01-01

    Receptor models generated by homology or even obtained by crystallography often have their binding pockets suboptimal for ligand docking and virtual screening applications due to insufficient accuracy or induced fit bias. Knowledge of previously discovered receptor ligands provides key information that can be used for improving docking and screening performance of the receptor. Here, we present a comprehensive ligand-guided receptor optimization (LiBERO) algorithm that exploits ligand information for selecting the best performing protein models from an ensemble. The energetically feasible protein conformers are generated through normal mode analysis and Monte Carlo conformational sampling. The algorithm allows iteration of the conformer generation and selection steps until convergence of a specially developed fitness function which quantifies the conformer's ability to select known ligands from decoys in a small-scale virtual screening test. Because of the requirement for a large number of computationally intensive docking calculations, the automated algorithm has been implemented to use Linux clusters allowing easy parallel scaling. Here, we will discuss the setup of LiBERO calculations, selection of parameters, and a range of possible uses of the algorithm which has already proven itself in several practical applications to binding pocket optimization and prospective virtual ligand screening.

  8. Molecular imaging of estrogen receptors

    NARCIS (Netherlands)

    van Kruchten, Michel

    2015-01-01

    For patients with estrogen receptor (ER) positive breast cancer, endocrine therapy plays a major role in both the adjuvant and palliative setting. For adequate treatment decision-making it is crucial to obtain up-to-date information on the ER-status of the tumor(s), since ER-expression is the sole

  9. Stability of solubilized benzodiazepine receptors

    NARCIS (Netherlands)

    Janssen, M.J; Ensing, K; de Zeeuw, R.A

    1997-01-01

    According to the observations of other researchers, benzodiazepine receptors solubilized with sodium deoxycholate are unstable, but stability can be improved by exchanging deoxycholate for Triton X-100. In our experiments we conclude that the choice of detergent is not the restrictive factor for the

  10. Uncompetitive antagonism of AMPA receptors

    DEFF Research Database (Denmark)

    Andersen, Trine F; Tikhonov, Denis B; Bølcho, Ulrik

    2006-01-01

    Philanthotoxins are uncompetitive antagonists of Ca2+-permeable AMPA receptors presumed to bind to the pore-forming region, but a detailed molecular mechanism for this interaction is missing. Here a small library of novel philanthotoxins was designed and synthesized using a solid-phase strategy. ...

  11. New horizons for lipoprotein receptors

    DEFF Research Database (Denmark)

    Andersen, Olav M.; Dagil, Robert; Kragelund, Birthe Brandt

    2013-01-01

    , this dogma has transformed with the observation that β-propellers of some LRs actively engage in complex formation too. Based on an in-depth decomposition of current structures and sequences, we suggest that exploitation of the β-propellers as binding targets depends on receptor subgroups. In particular, we...

  12. Virally encoded 7TM receptors

    DEFF Research Database (Denmark)

    Rosenkilde, M M; Waldhoer, M; Lüttichau, H R

    2001-01-01

    expression of this single gene in certain lymphocyte cell lineages leads to the development of lesions which are remarkably similar to Kaposi's sarcoma, a human herpesvirus 8 associated disease. Thus, this and other virally encoded 7TM receptors appear to be attractive future drug targets....

  13. Repeated blockade of mineralocorticoid receptors, but not of glucocorticoid receptors impairs food rewarded spatial learning

    NARCIS (Netherlands)

    Douma, BRK; Korte, SM; Buwalda, B; la Fleur, SE; Bohus, B; Luiten, PGM

    Corticosteroids from the adrenal cortex influence a variety of behaviours including cognition, learning and memory. These hormones act via two intracellular receptors, the mineralo-corticoid receptor (MR) and the glucocorticoid receptor (GR). These two receptor types display a high concentration and

  14. Repeated blockade of mineralocorticoid receptors, but not of glucocorticoid receptors impairs food rewarded spatial learning

    NARCIS (Netherlands)

    Douma, B. R.; Korte, S. M.; Buwalda, B.; La Fleur, S. E.; Bohus, B.; Luiten, P. G.

    1998-01-01

    Corticosteroids from the adrenal cortex influence a variety of behaviours including cognition, learning and memory. These hormones act via two intracellular receptors, the mineralo-corticoid receptor (MR) and the glucocorticoid receptor (GR). These two receptor types display a high concentration and

  15. The substance P/NK-1 receptor system: NK-1 receptor antagonists ...

    Indian Academy of Sciences (India)

    The substance P (SP)/neurokinin (NK)-1 receptor system plays an important role in cancer. SP promotes the proliferation of tumour cells, angiogenesis and the migration of tumour cells. We review the involvement of SP, the NK-1 receptor and NK-1 receptor antagonists in cancer. Tumour cells overexpress NK-1 receptors, ...

  16. Muscarinic receptors and drugs in cardiovascular medicine

    NARCIS (Netherlands)

    van Zwieten, P. A.; Doods, H. N.

    1995-01-01

    The parasympathetic system and its associated muscarinic receptors have been the subject of a renaissance of interest for the following two main reasons: (1) the association of endothelial muscarinic receptors and the nitric oxide (NO) pathway; (2) the discovery of several muscarinic receptor

  17. A new family of insect tyramine receptors

    DEFF Research Database (Denmark)

    Cazzamali, Giuseppe; Klærke, Dan Arne; Grimmelikhuijzen, Cornelis J P

    2005-01-01

    in the genomic databases from the malaria mosquito Anopheles gambiae and the honeybee Apis mellifera. These four tyramine or tyramine-like receptors constitute a new receptor family that is phylogenetically distinct from the previously identified insect octopamine/tyramine receptors. The Drosophila tyramine...

  18. Metabotropic glutamate receptors in glial cells

    NARCIS (Netherlands)

    D'Antoni, Simona; Berretta, Antonio; Bonaccorso, Carmela Maria; Bruno, Valeria; Aronica, Eleonora; Nicoletti, Ferdinando; Catania, Maria Vincenza

    2008-01-01

    Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system (CNS) and exerts its actions via a number of ionotropic glutamate receptors/channels and metabotropic glutamate (mGlu) receptors. In addition to being expressed in neurons, glutamate receptors are expressed in

  19. Neurotransmitter Receptor Binding in Bovine Cerebral Microvessels

    Science.gov (United States)

    Peroutka, Stephen J.; Moskowitz, Michael A.; Reinhard, John F.; Synder, Solomon H.

    1980-05-01

    Purified preparations of microvessels from bovine cerebral cortex contain substantial levels of alpha-adrenergic, beta-adrenergic, and histamine 1 receptor binding sites but only negligible serotonin, muscarinic cholinergic, opiate, and benzodiazepine receptor binding. Norepinephrine and histamine may be endogenous regulators of the cerebral microcirculation at the observed receptors.

  20. Imaging of receptors in clinical neurosciences

    NARCIS (Netherlands)

    Korf, J

    This article deals with the question why should one determine receptors in the brain with positron and single photon emission tomography (PET and SPECT, respectively). Radiopharmaceuticals for a wide variety of receptors are available now. Receptors studies with PET and SPECT have thus far focused

  1. TiB2 Katkılı B4C-SiC Kompozit Malzemelerin Co-60 Gama Radyoizotop Kaynağı Karşısındaki Davranışlarının İncelenmesi

    Directory of Open Access Journals (Sweden)

    Bülent Büyük

    2015-02-01

    Full Text Available Bu çalışmada titanyum diborür (TiB2 katkılı bor karbür (B4C-silisyum karbür (SiC kompozit malzemelerin Co-60 gama radyoizotop kaynağı karşısındaki radyasyon zayıflatma davranışları incelenmiştir. Deneylerde TiB2 katkısı olmayan B4C-SiC kompozit malzeme ile hacimce %2 ve %4 TiB2 katkılı B4C-SiC kompozit malzemeler kullanılmıştır. Bütün malzemelerde hacimce B4C/SiC oranı 6/4’tür. İki farklı enerji pikine sahip olan (1.17 ve 1.33 MeV Co-60 gama radyoizotop kaynağına ilişkin malzemelerin zayıflatma eğrileri çizilmiş ve lineer zayıflatma katsayıları hesaplanmıştır. Buradan hareketle malzemelerin kütle zayıflatma katsayıları ve yarı-değer kalınlıkları (YDK elde edilmiştir. Deneylerden elde edilen kütle zayıflatma katsayıları, XCOM bilgisayar programı kullanılarak hesaplanan teorik kütle zayıflatma katsayıları ile karşılaştırılmıştır. Ayrıca elde edilen yarı-değer kalınlıkları birbirleri ile mukayeseli olarak değerlendirilmiştir. Bu bağlamda deneysel kütle zayıflatma katsayılarının, teorik olarak (XCOM hesaplanan değerler ile uyumlu olduğu ve farkın %10’un altında kaldığı görülmüştür. Ayrıca TiB2 katkılı B4C-SiC kompozit malzemelerin katkısız olanlara göre daha düşük YDK değerlerine sahip olduğu ortaya çıkarılmıştır. Ek olarak %4 TiB2 katkılı B4C-SiC kompozit malzemelerin %2 TiB2 katkılı B4C-SiC kompozit malzemelere göre daha düşük YDK değerlerine sahip olduğu gözlenmiştir. TiB2 katkısının yapılmasının ve TiB2 oranının artırılmasının B4C-SiC kompozit malzemelerin Co-60 gama kaynağı karşısındaki radyasyon zırhlama kabiliyetini artırdığı ortaya çıkarılmıştır.

  2. Modified Receptor Internalization upon Coexpression of 5-HT1B Receptor and 5-HT2B Receptors

    OpenAIRE

    Janoshazi , Agnes; Deraet , Maud; Callebert , Jacques; Setola , Vincent; Guenther , Silke; Saubamea , Bruno; Manivet , Philippe; Launay , Jean-Marie; Maroteaux , Luc

    2007-01-01

    International audience; Serotonin 5-HT(2B) receptors are often coexpressed with 5-HT(1B) receptors, and cross-talk between the two receptors has been reported in various cell types. However, many mechanistic details underlying 5-HT(1B) and 5-HT(2B) receptor cross-talk have not been elucidated. We hypothesized that 5-HT(2B) and 5-HT(1B) receptors each affect the others' signaling by modulating the others' trafficking. We thus examined the agonist stimulated internalization kinetics of fluoresc...

  3. Different NK cell-activating receptors preferentially recruit Rab27a or Munc13-4 to perforin-containing granules for cytotoxicity

    DEFF Research Database (Denmark)

    Wood, Stephanie M; Meeths, Marie; Chiang, Samuel C C

    2009-01-01

    of perforin-containing lytic granules induced by signals for natural and antibody-dependent cellular cytotoxicity. We demonstrate here that these signals fail to induce degranulation in resting NK cells from Rab27a-deficient patients. In resting NK cells from healthy subjects, endogenous Rab27a and Munc13...... functional antigen-1, NKG2D, or 2B4 induced colocalization of Rab27a, but not Munc13-4, with perforin. Conversely, engagement of antibody-dependent cellular cytotoxicity receptor CD16 induced colocalization of Munc13-4, but not Rab27a, with perforin. Furthermore, colocalization of Munc13-4 with perforin...

  4. Triheteromeric NMDA Receptors at Hippocampal Synapses

    Science.gov (United States)

    Tovar, Kenneth R.; McGinley, Matthew J.; Westbrook, Gary L.

    2013-01-01

    NMDA receptors are composed of two GluN1 (N1) and two GluN2 (N2) subunits. Constituent N2 subunits control the pharmacological and kinetic characteristics of the receptor. NMDA receptors in hippocampal or cortical neurons are often thought of as diheteromeric, i.e., containing only one type of N2 subunit. However, triheteromeric receptors with more than one type of N2 subunit also have been reported and the relative contribution of di- and triheteromeric NMDA receptors at synapses has been difficult to assess. Because wild-type hippocampal principal neurons express N1, N2A and N2B, we used cultured hippocampal principal neurons from N2A and N2B-knockout mice as templates for diheteromeric synaptic receptors. Summation of N1/N2B and N1/N2A excitatory postsynaptic currents could not account for the deactivation kinetics of wild-type excitatory postsynaptic currents (EPSCs) however. To make a quantitative estimate of NMDA receptor subtypes at wild-type synapses, we used the deactivation kinetics, as well as the effects of the competitive antagonist NVP-AAM077. Our results indicate that three types of NMDA receptors contribute to the wild-type EPSC, with at least two-thirds being triheteromeric receptors. Functional isolation of synaptic triheteromeric receptors revealed deactivation kinetics and pharmacology distinct from either diheteromeric receptor subtype. Because of differences in open probability, synaptic triheteromeric receptors outnumbered N1/N2A receptors by 5.8 to 1 and N1/N2B receptors by 3.2 to 1. Our results suggest that triheteromeric NMDA receptors must be either preferentially assembled or preferentially localized at synapses. PMID:23699525

  5. Some theoretical aspects of hormone receptor determination

    International Nuclear Information System (INIS)

    Sluiter, W.J.

    1981-01-01

    Suitable antisera for determination of hormone receptors are not available for the majority of hormone receptors. Therefore, the determination of hormone receptors is mostly performed in terms of binding capacity for the appropriate hormone, using radioactive hormone labels. Some theoretical aspects of such a receptor determination are discussed including the length of incubation (total or unoccupied receptor concentration), single point or multiple point (Scatchard) analysis (regarding the influence of other specific binders), the correction procedure for non-specific binding and the influence of the circulating hormone level. (Auth.)

  6. Chapter 8. Activation mechanisms of chemokine receptors

    DEFF Research Database (Denmark)

    Jensen, Pia C; Rosenkilde, Mette M

    2009-01-01

    Chemokine receptors belong to the large family of 7-transmembrane (7TM) G-protein-coupled receptors. These receptors are targeted and activated by a variety of different ligands, indicating that activation is a result of similar molecular mechanisms but not necessarily similar modes of ligand...... binding. Attempts to unravel the activation mechanism of 7TM receptors have led to the conclusion that activation involves movements of the transmembrane segments VI and VII in particular, as recently gathered in the Global Toggle Switch Model. However, to understand the activation mechanism completely......, more research has to be done in this field. Chemokine receptors are interesting tools in this matter. First, the chemokine system has a high degree of promiscuity that allows several chemokines to target one receptor in different ways, as well as a single chemokine ligand to target several receptors...

  7. DMPD: Signal transduction by the lipopolysaccharide receptor, Toll-like receptor-4. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15379975 Signal transduction by the lipopolysaccharide receptor, Toll-like receptor... Signal transduction by the lipopolysaccharide receptor, Toll-like receptor-4. PubmedID 15379975 Title Signa...l transduction by the lipopolysaccharide receptor, Toll-like receptor-4. Authors

  8. Further characterization of tuftsin receptors

    Energy Technology Data Exchange (ETDEWEB)

    Bump, N.J.; Lee, J.; Najjar, V.A.

    1986-03-05

    Tuftsin receptor was purified from rabbit peritoneal granulocytes by affinity chromatography. The pentapeptide analog, Thr-Lys-Pro-Pro-Arg was covalently linked to a solid support column. Rabbit granulocyte membrane was prepared, dissolved in 8 mM CHAPS and run through the column, eluted with 20 eta M free pentapeptide and subjected to dialysis concentration. When this was run on SDS-PAGE, two bands were obtained at a migration equivalent to Mr 60 and 62 K. These were electroblotted on nitrocellulose paper which showed two corresponding (/sup 3/H)-tuftsin binding bands. After reduction, and boiling, SDS-PAGE runs showed two bands Mr 85 and 70 K. When the purified receptor was reduced, alkylated and treated with endo-..beta..-N-acetylglucosaminidase H, only one band was obtained at Mr of about 90 K.

  9. Ketamine: NMDA Receptors and Beyond

    OpenAIRE

    Zorumski, Charles F.; Izumi, Yukitoshi; Mennerick, Steven

    2016-01-01

    Human studies examining the effects of the dissociative anesthetic ketamine as a model for psychosis and as a rapidly acting antidepressant have spurred great interest in understanding ketamine's actions at molecular, cellular, and network levels. Although ketamine has unequivocal uncompetitive inhibitory effects on N-methyl-d-aspartate receptors (NMDARs) and may preferentially alter the function of NMDARs on interneurons, recent work has questioned whether block of NMDARs is critical for its...

  10. Assay for the glucagon receptor

    International Nuclear Information System (INIS)

    Rojas, F.J.; Birnbaumer, L.

    1985-01-01

    A new iodination procedure for glucagon using 1,3,4,6-tetracholoro-3α,6α-diphenylglycouril (Iodogen) as the oxidizing agent, and the subsequent separation in pure form of [ 125 I-Tyr 10 ]mono-iodoglucagon by reverse-phase high-pressure liquid chromatography (HPLC) over C 18 -μ Bondapak columns is described. The newly synthesized [ 125 I]mono-iodoglucagon is shown to be a suitable probe for studying structural and functional properties of glucagon receptors

  11. Keratinocyte cytokine and chemokine receptors.

    Science.gov (United States)

    Tüzün, Yalçin; Antonov, Meltem; Dolar, Neslihan; Wolf, Ronni

    2007-10-01

    Chemokines are a superfamily of small, secreted proteins that regulate cell traffic in homeostatic and inflammatory conditions. Keratinocytes synthesize many chemokines, including members of the CC and CXC subfamilies, such as regulated on activation of normal T-cell expressed and secreted, gamma-interferon inducible protein-10, monokine induced by gamma-interferon, and thymus- and activation-regulated chemokine. They also express some chemokine receptors that mediate the inflammatory or immune response by attracting various kinds of leukocytes.

  12. Insulin receptor in Drosophila melanogaster

    International Nuclear Information System (INIS)

    Petruzzelli, L.; Herrera, R.; Rosen, O.

    1986-01-01

    A specific, high affinity insulin receptor is present in both adult Drosophila and in Drosophila embryos. Wheat germ lectin-enriched extracts of detergent-solubilized membranes from embryos and adults bind insulin with a K/sub d/ of 15 nM. Binding is specific for insulin; micromolar concentrations of proinsulin, IGFI, and IGFII are required to displace bound 125 I-insulin. Insulin-dependent protein tyrosine kinase activity appears during embryogenesis. It is evident between 6 and 12 hours of development, peaks between 12 and 18 hours and falls in the adult. During 0-6 hours of embryogenesis, and in the adult, a specific protein band (Mr = 135,000) is crosslinked to 125 I-insulin. During 6-12 and 12-18 hours of embryogenesis stages in which insulin-dependent protein tyrosine kinase is high, an additional band (Mr = 100,000) becomes crosslinked to 125 I-insulin. Isolation and DNA sequence analysis of genomic clones encoding the Drosophila insulin receptor will be presented as will the characterization of insulin receptor mRNA's during development

  13. PAF receptor structure: a hypothesis.

    Science.gov (United States)

    Godfroid, J J; Dive, G; Lamotte-Brasseur, J; Batt, J P; Heymans, F

    1991-12-01

    Different hypotheses of the structure of platelet-activating factor (PAF) receptor based on structure-activity relationships of agonists and antagonists are reviewed. For an agonistic effect, strong hydrophobic interactions and an ether function are required in position-1 of the glycerol backbone; chain length limitations and steric hindrance demand a small group in position-2. The unusual structural properties of non-PAF-like antagonists required 3-D electrostatic potential calculations. This method applied to seven potent antagonists suggests a strong "Cache-orielles" (ear-muff) effect, i.e., two strong electronegative wells (isocontour at -10 Kcal/mole) are located at 180 degrees to each other and at a relatively constant distance. Initial consideration of the "Cache-oreilles" effect implied the structure of a bipolarized cylinder of 10-12 A diameter for the receptor. However, very recent results on studies with agonists and antagonists structurally similar to PAF suggest that the receptor may in fact be a multi-polarized cylinder.

  14. NGA/Insulin receptor scanning

    International Nuclear Information System (INIS)

    Kurtaran, A.; Virgolini, I.

    1994-01-01

    Tc-99m-galactosyl-neoglycoalbumin (NGA) is one of the first receptor-based radiopharmaceuticals which specifically recognizes the hepatic binding protein (HBP) located on the surface of the hepatocytes. The exclusive interactin of NGA with HBP provided the basis for a kinetic model for the evaluation hepatocellular function. During the last years we have used NGA in more than 300 patients with various liver diseases including liver cirrhosis (Stages Child A to Child C), viral hepatitis, and carcinomas. In these studies, the calculated HBP densities, after i.v.-injection of Tc-99m-NGA, significantly correlated with the clinical course of the diseases. Furthermore, similar to conventional Tc-colloid, NGA provided excellent demonstration of 'cold spots' for hepatic masses. In a further approach we used another hepatocyte receptor-seeking radioligand, I-123-Tyr-A14- insulin, and found, that its in vitro-binding to hepatocellular carcinomas is greatly enhanced over normal hepatic tissue. On this basis, we developed a double-tracer method using NGA and insulin in a single study. Thus, areas of 'cold spots' identifying hepatic masses on NGA scans, take up I-123-Tyr-A14-insulin immediately after i.v.-injection. This was true for hepatocellular hepatomas, but not for adenocarcinomas. In conclusion, NGA/insulin receptor scanning could be a novel and save method for the demonstration of hepatocellular hepatomas. (author)

  15. Lymphocyte receptors for pertussis toxin

    Energy Technology Data Exchange (ETDEWEB)

    Clark, C.G.; Armstrong, G.D. (Univ. of Alberta, Edmonton (Canada))

    1990-12-01

    We have investigated human T-lymphocyte receptors for pertussis toxin by affinity isolation and photoaffinity labeling procedures. T lymphocytes were obtained from peripheral human blood, surface iodinated, and solubilized in Triton X-100. The iodinated mixture was then passed through pertussis toxin-agarose, and the fractions were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Autoradiography of the fixed, dried gels revealed several bands in the pertussis toxin-bound fraction that were not observed in fractions obtained from histone or fetuin-agarose. Further investigations employed a photoaffinity labeling reagent, sulfosuccinimidyl 2-(p-azido-salicylamido)-1,3'-dithiopropionate, to identify pertussis toxin receptors in freshly isolated peripheral blood monocytic cells, T lymphocytes, and Jurkat cells. In all three cell systems, the pertussis toxin affinity probe specifically labeled a single protein species with an apparent molecular weight of 70,000 that was not observed when the procedure was performed in the presence of excess unmodified pertussis toxin. A protein comparable in molecular weight to the one detected by the photoaffinity labeling technique was also observed among the species that bound to pertussis toxin-agarose. The results suggest that pertussis toxin may bind to a 70,000-Da receptor in human T lymphocytes.

  16. Nuclear receptors for thyroid hormones

    International Nuclear Information System (INIS)

    Ricketts, M.H.; Groenewald, J. de W.; Wilson, B.D.

    1980-01-01

    The thyroid hormones, T 3 and T 4 , modulate a vast number of metabolic processes in mammalian tissues. High affinity, low capacity binding sites for T 3 and T 4 have been demonstrated in cell nuclei of target organs using both in vivo and in vitro labelling techniques. The displacement of [ 125 I]T 3 from nuclear binding sites by thyroid hormone analogues correlates well with the thyromimetic activities of the analogues tested. Dose-response relationships between T 3 occupancy and growth hormone secretion as a function of free T 3 concentration have been established with the GH 1 cell line. The equilibrium dissociation constant of the equation which describes how T 3 binds to the nuclei of intact cells is essentially the same as the free T 3 concentration that elicits the half-maximal biological response of the hormone. It is becoming apparent that these nuclear binding sites represent specific thyroid hormone receptors, whose function may be to regulate gene activity in target tissues. This report concerns the binding of the rat liver nuclear receptor to duplex and random coil DNA as well as to non-mammalian and synthetic DNAs. We postulate that the receptor binds in vivo to native DNA in the minor groove of the DNA helix

  17. Complex GABAB receptor complexes: how to generate multiple functionally distinct units from a single receptor

    Directory of Open Access Journals (Sweden)

    Chanjuan eXU

    2014-02-01

    Full Text Available The main inhibitory neurotransmitter, GABA, acts on both ligand-gated and G protein-coupled receptors, the GABAA/C and GABAB receptors, respectively. The later play important roles in modulating many synapses, both at the pre- and post-synaptic levels, and are then still considered as interesting targets to treat a number of brain diseases, including addiction. For many years, several subtypes of GABAB receptors were expected, but cloning revealed only two genes that work in concert to generate a single type of GABAB receptor composed of two subunits. Here we will show that the signaling complexity of this unit receptor type can be largely increased through various ways, including receptor stoichiometry, subunit isoforms, membrane expression and localization, crosstalk with other receptors or interacting proteins. These recent data revealed how complexity of a receptor unit can be increased, observation that certainly are not unique to the GABAB receptor.

  18. The two-state dimer receptor model: a general model for receptor dimers.

    Science.gov (United States)

    Franco, Rafael; Casadó, Vicent; Mallol, Josefa; Ferrada, Carla; Ferré, Sergi; Fuxe, Kjell; Cortés, Antoni; Ciruela, Francisco; Lluis, Carmen; Canela, Enric I

    2006-06-01

    Nonlinear Scatchard plots are often found for agonist binding to G-protein-coupled receptors. Because there is clear evidence of receptor dimerization, these nonlinear Scatchard plots can reflect cooperativity on agonist binding to the two binding sites in the dimer. According to this, the "two-state dimer receptor model" has been recently derived. In this article, the performance of the model has been analyzed in fitting data of agonist binding to A(1) adenosine receptors, which are an example of receptor displaying concave downward Scatchard plots. Analysis of agonist/antagonist competition data for dopamine D(1) receptors using the two-state dimer receptor model has also been performed. Although fitting to the two-state dimer receptor model was similar to the fitting to the "two-independent-site receptor model", the former is simpler, and a discrimination test selects the two-state dimer receptor model as the best. This model was also very robust in fitting data of estrogen binding to the estrogen receptor, for which Scatchard plots are concave upward. On the one hand, the model would predict the already demonstrated existence of estrogen receptor dimers. On the other hand, the model would predict that concave upward Scatchard plots reflect positive cooperativity, which can be neither predicted nor explained by assuming the existence of two different affinity states. In summary, the two-state dimer receptor model is good for fitting data of binding to dimeric receptors displaying either linear, concave upward, or concave downward Scatchard plots.

  19. Characterization of astrocytic and neuronal benzodiazepine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Bender, A.S.

    1988-01-01

    Primary cultures of astrocytes and neurons express benzodiazepine receptors. Neuronal benzodiazepine receptors were of high-affinity, K{sub D} values were 7.5-43 nM and the densities of receptors (B{sub max}) were 924-4131 fmol/mg protein. Astrocytes posses a high-affinity benzodiazepine receptor, K{sub D} values were 6.6-13 nM. The B{sub max} values were 6,033-12,000 fmol/mg protein. The pharmacological profile of the neuronal benzodiazepine receptor was that of the central-type benzodiazepine receptor, where clonazepam has a high-affinity and Ro 5-4864 (4{prime}-chlorodiazepam) has a low-affinity. Whereas astrocytic benzoidazepine receptor was characteristic of the so called peripheral-type benzodiazepine receptors, which shows a high-affinity towards Ro 5-4863, and a low-affinity towards clonazepam. The astrocytic benzodiazepine receptors was functionally correlated with voltage dependent calcium channels, since dihydropyridines and benzodiazepines interacted with ({sup 3}H) diazepam and ({sup 3}H) nitrendipine receptors with the same rank order of potency, showing a statistically significant correlation. No such correlation was observed in neurons.

  20. Localization of mineralocorticoid receptors at mammalian synapses.

    Directory of Open Access Journals (Sweden)

    Eric M Prager

    Full Text Available In the brain, membrane associated nongenomic steroid receptors can induce fast-acting responses to ion conductance and second messenger systems of neurons. Emerging data suggest that membrane associated glucocorticoid and mineralocorticoid receptors may directly regulate synaptic excitability during times of stress when adrenal hormones are elevated. As the key neuron signaling interface, the synapse is involved in learning and memory, including traumatic memories during times of stress. The lateral amygdala is a key site for synaptic plasticity underlying conditioned fear, which can both trigger and be coincident with the stress response. A large body of electrophysiological data shows rapid regulation of neuronal excitability by steroid hormone receptors. Despite the importance of these receptors, to date, only the glucocorticoid receptor has been anatomically localized to the membrane. We investigated the subcellular sites of mineralocorticoid receptors in the lateral amygdala of the Sprague-Dawley rat. Immunoblot analysis revealed the presence of mineralocorticoid receptors in the amygdala. Using electron microscopy, we found mineralocorticoid receptors expressed at both nuclear including: glutamatergic and GABAergic neurons and extra nuclear sites including: presynaptic terminals, neuronal dendrites, and dendritic spines. Importantly we also observed mineralocorticoid receptors at postsynaptic membrane densities of excitatory synapses. These data provide direct anatomical evidence supporting the concept that, at some synapses, synaptic transmission is regulated by mineralocorticoid receptors. Thus part of the stress signaling response in the brain is a direct modulation of the synapse itself by adrenal steroids.

  1. Protein Connectivity in Chemotaxis Receptor Complexes.

    Directory of Open Access Journals (Sweden)

    Stephan Eismann

    2015-12-01

    Full Text Available The chemotaxis sensory system allows bacteria such as Escherichia coli to swim towards nutrients and away from repellents. The underlying pathway is remarkably sensitive in detecting chemical gradients over a wide range of ambient concentrations. Interactions among receptors, which are predominantly clustered at the cell poles, are crucial to this sensitivity. Although it has been suggested that the kinase CheA and the adapter protein CheW are integral for receptor connectivity, the exact coupling mechanism remains unclear. Here, we present a statistical-mechanics approach to model the receptor linkage mechanism itself, building on nanodisc and electron cryotomography experiments. Specifically, we investigate how the sensing behavior of mixed receptor clusters is affected by variations in the expression levels of CheA and CheW at a constant receptor density in the membrane. Our model compares favorably with dose-response curves from in vivo Förster resonance energy transfer (FRET measurements, demonstrating that the receptor-methylation level has only minor effects on receptor cooperativity. Importantly, our model provides an explanation for the non-intuitive conclusion that the receptor cooperativity decreases with increasing levels of CheA, a core signaling protein associated with the receptors, whereas the receptor cooperativity increases with increasing levels of CheW, a key adapter protein. Finally, we propose an evolutionary advantage as explanation for the recently suggested CheW-only linker structures.

  2. Amphipathic benzenes are designed inhibitors of the estrogen receptor alpha/steroid receptor coactivator interaction.

    Science.gov (United States)

    Gunther, Jillian R; Moore, Terry W; Collins, Margaret L; Katzenellenbogen, John A

    2008-05-16

    We report here on the design, synthesis, and evaluation of small molecule inhibitors of the interaction between a steroid receptor coactivator and estrogen receptor alpha. These inhibitors are based upon an amphipathic benzene scaffold whose hydrophobic face mimics the leucine-rich alpha-helical consensus sequence on the steroid receptor coactivators that interacts with a shallow groove on estrogen receptor alpha. Several of these molecules are among the most potent inhibitors of this interaction described to date and are active at low micromolar concentrations in both in vitro models of estrogen receptor action and in cell-based assays of estrogen receptor-mediated coactivator interaction and transcription.

  3. Activation of glucocorticoid receptors increases 5-HT2A receptor levels

    DEFF Research Database (Denmark)

    Trajkovska, Viktorija; Kirkegaard, Lisbeth; Krey, Gesa

    2009-01-01

    of depression is unknown. In mice with altered glucocorticoid receptor (GR) expression we investigated 5-HT2A receptor levels by Western blot and 3H-MDL100907 receptor binding. Serotonin fibre density was analyzed by stereological quantification of serotonin transporter immunopositive fibers. To establish...... an effect of GR activation on 5-HT2A levels, mature organotypic hippocampal cultures were exposed to corticosterone with or without GR antagonist mifepristone and mineralocorticoid receptor (MR) antagonist spironolactone. In GR under-expressing mice, hippocampal 5-HT2A receptor protein levels were decreased...... in dorsal hippocampus (77 +/- 35%, p effect of GR activation on 5-HT2A receptor...

  4. Role of nicotine dependence on the relationship between variants in the nicotinic receptor genes and risk of lung adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Tung-Sung Tseng

    Full Text Available Several variations in the nicotinic receptor genes have been identified to be associated with both lung cancer risk and smoking in the genome-wide association (GWA studies. However, the relationships among these three factors (genetic variants, nicotine dependence, and lung cancer remain unclear. In an attempt to elucidate these relationships, we applied mediation analysis to quantify the impact of nicotine dependence on the association between the nicotinic receptor genetic variants and lung adenocarcinoma risk. We evaluated 23 single nucleotide polymorphisms (SNPs in the five nicotinic receptor related genes (CHRNB3, CHRNA6, and CHRNA5/A3/B4 previously reported to be associated with lung cancer risk and smoking behavior and 14 SNPs in the four 'control' genes (TERT, CLPTM1L, CYP1A1, and TP53, which were not reported in the smoking GWA studies. A total of 661 lung adenocarcinoma cases and 1,347 controls with a smoking history, obtained from the Environment and Genetics in Lung Cancer Etiology case-control study, were included in the study. Results show that nicotine dependence is a mediator of the association between lung adenocarcinoma and gene variations in the regions of CHRNA5/A3/B4 and accounts for approximately 15% of this relationship. The top two CHRNA3 SNPs associated with the risk for lung adenocarcinoma were rs1051730 and rs12914385 (p-value = 1.9×10(-10 and 1.1×10(-10, respectively. Also, these two SNPs had significant indirect effects on lung adenocarcinoma risk through nicotine dependence (p = 0.003 and 0.007. Gene variations rs2736100 and rs2853676 in TERT and rs401681 and rs31489 in CLPTM1L had significant direct associations on lung adenocarcinoma without indirect effects through nicotine dependence. Our findings suggest that nicotine dependence plays an important role between genetic variants in the CHRNA5/A3/B4 region, especially CHRNA3, and lung adenocarcinoma. This may provide valuable information for

  5. Receptor Tyrosine Kinases in Drosophila Development

    Science.gov (United States)

    Sopko, Richelle; Perrimon, Norbert

    2013-01-01

    Tyrosine phosphorylation plays a significant role in a wide range of cellular processes. The Drosophila genome encodes more than 20 receptor tyrosine kinases and extensive studies in the past 20 years have illustrated their diverse roles and complex signaling mechanisms. Although some receptor tyrosine kinases have highly specific functions, others strikingly are used in rather ubiquitous manners. Receptor tyrosine kinases regulate a broad expanse of processes, ranging from cell survival and proliferation to differentiation and patterning. Remarkably, different receptor tyrosine kinases share many of the same effectors and their hierarchical organization is retained in disparate biological contexts. In this comprehensive review, we summarize what is known regarding each receptor tyrosine kinase during Drosophila development. Astonishingly, very little is known for approximately half of all Drosophila receptor tyrosine kinases. PMID:23732470

  6. Acetylcholine receptors in the human retina

    International Nuclear Information System (INIS)

    Hutchins, J.B.; Hollyfield, J.G.

    1985-01-01

    Evidence for a population of acetylcholine (ACh) receptors in the human retina is presented. The authors have used the irreversible ligand 3 H-propylbenzilylcholine mustard ( 3 H-PrBCM) to label muscarinic receptors. 3 H- or 125 I-alpha-bungarotoxin (alpha-BTx) was used to label putative nicotinic receptors. Muscarinic receptors are apparently present in the inner plexiform layer of the retina. Autoradiographic grain densities are reduced in the presence of saturating concentrations of atropine, quinuclidinyl benzilate or scopolamine; this indicates that 3 H-PrBCM binding is specific for a population of muscarinic receptors in the human retina. Binding sites for radiolabeled alpha-BTx are found predominantly in the inner plexiform layer of the retina. Grain densities are reduced in the presence of d-tubocurarine, indicating that alpha-BTx may bind to a pharmacologically relevant nicotinic ACh receptor. This study provides evidence for cholinergic neurotransmission in the human retina

  7. Characteristic molecular vibrations of adenosine receptor ligands.

    Science.gov (United States)

    Chee, Hyun Keun; Yang, Jin-San; Joung, Je-Gun; Zhang, Byoung-Tak; Oh, S June

    2015-02-13

    Although the regulation of membrane receptor activation is known to be crucial for molecular signal transduction, the molecular mechanism underlying receptor activation is not fully elucidated. Here we study the physicochemical nature of membrane receptor behavior by investigating the characteristic molecular vibrations of receptor ligands using computational chemistry and informatics methods. By using information gain, t-tests, and support vector machines, we have identified highly informative features of adenosine receptor (AdoR) ligand and corresponding functional amino acid residues such as Asn (6.55) of AdoR that has informative significance and is indispensable for ligand recognition of AdoRs. These findings may provide new perspectives and insights into the fundamental mechanism of class A G protein-coupled receptor activation. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  8. Subtype selective kainic acid receptor agonists

    DEFF Research Database (Denmark)

    Bunch, Lennart; Krogsgaard-Larsen, Povl

    2009-01-01

    (S)-Glutamic acid (Glu) is the major excitatory neurotransmitter in the mammalian central nervous system, activating the plethora of glutamate receptors (GluRs). In broad lines, the GluRs are divided into two major classes: the ionotropic Glu receptors (iGluRs) and the metabotropic Glu receptors (m......GluRs). Within the iGluRs, five subtypes (KA1, KA2, iGluR5-7) show high affinity and express full agonist activity upon binding of the naturally occurring amino acid kainic acid (KA). Thus these receptors have been named the KA receptors. This review describes all-to our knowledge-published KA receptor agonists...

  9. Androgen receptor in estrogen receptor positive breast cancer: Beyond expression.

    Science.gov (United States)

    Basile, Debora; Cinausero, Marika; Iacono, Donatella; Pelizzari, Giacomo; Bonotto, Marta; Vitale, Maria Grazia; Gerratana, Lorenzo; Puglisi, Fabio

    2017-12-01

    In recent years, new therapeutic approaches have reshaped the overall strategy of breast cancer (BC) treatment and have markedly improved patient survival. This is, in part, due to novel therapies for estrogen receptor (ER)-positive BC. Unfortunately, many patients present de novo resistance to these therapies or develop an acquired resistance over time. Therefore, research is now focused on discovering new molecular targets to overcome these resistances. Interestingly, preclinical and clinical studies have shown a critical role for the cross-talk between androgen receptor (AR) and ER in luminal-like BC. AR is expressed in >60% of BC and in up to 90% of ERα-positive tumors. Multiple studies suggest that AR is associated with a favorable prognosis. However, AR overexpression and, in particular, the high AR:ER ratio, seem to be involved in resistance to hormonal treatment. In this setting, a group of BCs could benefit from AR-inhibitors; nevertheless, some ER-positive BC patients do not seem to benefit from this strategy. Therefore, it is crucial to identify biomarkers that would enable the selection of patients who might benefit from combination treatment with ER and AR inhibitors. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Xenobiotics and the Glucocorticoid Receptor.

    Science.gov (United States)

    Gulliver, Linda S M

    2017-03-15

    Glucocorticoid Receptor (GR) is present in virtually every human cell type. Representing a nuclear receptor superfamily, GR has several different isoforms essentially acting as ligand-dependent transcription factors, regulating glucocorticoid-responsive gene expression in both a positive and a negative manner. Although the natural ligand of the Glucocorticoid Receptor, glucocorticoids (GC) represent only some of the multiple ligands for GR. Xenobiotics, ubiquitous in the environment, bind to GR and are also capable of activating or repressing GR gene expression, thereby modulating GR cell and tissue-specific downstream effects in a multitude of ways that include responses to inflammatory, allergic, metabolic, neoplastic and autoimmune processes. Many xenobiotics, if inadequately metabolized by xenobiotic metabolizing enzymes and not wholly eliminated, could have deleterious toxic effects with potentially lethal consequences. This review examines GR, the genomic and non-genomic actions of natural and synthetic GC and the body's handling of xenobiotic compounds, before reviewing what is presently known about GR's interactions with many of the more commonly encountered and some of the less well known GR-associated xenobiotics. GR promiscuity and crosstalk with other signaling pathways is discussed, alongside novel roles for GR that include mood disorder and addiction. A knowledge of GR interactions with xenobiotics is increasingly relevant when considering aging populations and the related prevalence of neoplastic disease, together with growing concerns around human exposure to mixtures of chemicals in the environment. Furthermore, escalating rates of obesity, Type 2 diabetes; autoimmune, allergy, addiction and mood disorder-related pathologies, require novel targeted interventions and GR appears a promising pharmacological candidate. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. NUREBASE: database of nuclear hormone receptors

    OpenAIRE

    Duarte, Jorge; Perrière, Guy; Laudet, Vincent; Robinson-Rechavi, Marc

    2002-01-01

    Nuclear hormone receptors are an abundant class of ligand activated transcriptional regulators, found in varying numbers in all animals. Based on our experience of managing the official nomenclature of nuclear receptors, we have developed NUREBASE, a database containing protein and DNA sequences, reviewed protein alignments and phylogenies, taxonomy and annotations for all nuclear receptors. The reviewed NUREBASE is completed by NUREBASE_DAILY, automatically updated every 24 h. Both databases...

  12. Progesterone receptor modulators in breast cancer

    OpenAIRE

    WIEHLE, Ronald D.

    2015-01-01

    Breast cancer has been treated successfully with selective estrogen receptor antagonists (SERMs) such as tamoxifen, receptor-depleting agents such as fulvestrant, and aromatase inhibitors such as anastrozole. Selective progesterone receptor modulators (SPRMs or PRMs) have not been studied as much and are currently under investigation for inhibition of mammary carcinogenesis in animal models and breast cancer prevention trials in women. They might follow tamoxifen and aromatase inhibitors in t...

  13. Hemoglobin and heme scavenger receptors

    DEFF Research Database (Denmark)

    Nielsen, Marianne Jensby; Møller, Holger Jon; Moestrup, Søren Kragh

    2010-01-01

    Heme, the functional group of hemoglobin, myoglobin, and other hemoproteins, is a highly toxic substance when it appears in the extracellular milieu. To circumvent potential harmful effects of heme from hemoproteins released during physiological or pathological cell damage (such as hemolysis...... and rhabdomyolysis), specific high capacity scavenging systems have evolved in the mammalian organism. Two major systems, which essentially function in a similar way by means of a circulating latent plasma carrier protein that upon ligand binding is recognized by a receptor, are represented by a) the hemoglobin...

  14. CERAPP: Collaborative Estrogen Receptor Activity Prediction Project

    Data.gov (United States)

    U.S. Environmental Protection Agency — Data from a large-scale modeling project called CERAPP (Collaborative Estrogen Receptor Activity Prediction Project) demonstrating using predictive computational...

  15. Human dopamine receptor and its uses

    Energy Technology Data Exchange (ETDEWEB)

    Civelli, Olivier (Portland, OR); Van Tol, Hubert Henri-Marie (Toronto, CA)

    1999-01-01

    The present invention is directed toward the isolation, characterization and pharmacological use of the human D4 dopamine receptor. The nucleotide sequence of the gene corresponding to this receptor and alleleic variant thereof are provided by the invention. The invention also includes recombinant eukaryotic expression constructs capable of expressing the human D4 dopamine receptor in cultures of transformed eukaryotic cells. The invention provides cultures of transformed eukaryotic cells which synthesize the human D4 dopamine receptor, and methods for characterizing novel psychotropic compounds using such cultures.

  16. Characterization of the chicken muscle insulin receptor

    International Nuclear Information System (INIS)

    Adamo, M.; Simon, J.; Rosebrough, R.W.; McMurtry, J.P.; Steele, N.C.; LeRoith, D.

    1987-01-01

    Insulin receptors are present in chicken skeletal muscle. Crude membrane preparations demonstrated specific 125 I-insulin binding. The nonspecific binding was high (36-55% of total binding) and slightly lower affinity receptors were found than are typically observed for crude membrane insulin binding in other chicken tissues. Affinity crosslinking of 125 I-insulin to crude membranes revealed insulin receptor alpha-subunits of Mr 128K, intermediate between those of liver (134K) and brain (124K). When solubilized and partially purified on wheat germ agglutinin (WGA) affinity columns, chicken muscle insulin receptors exhibited typical high affinity binding, with approximately 10(-10) M unlabeled insulin producing 50% inhibition of the specific 125 I-insulin binding. WGA purified chicken muscle insulin receptors also exhibited insulin-stimulated autophosphorylation of the beta-subunit, which appeared as phosphorylated bands of 92- and 81K. Both bands were immunoprecipitated by anti-receptor antiserum (B10). WGA purified membranes also demonstrated dose-dependent insulin-stimulated phosphorylation of the exogenous substrate poly(Glu,Tyr)4:1. However, unlike chicken liver, chicken muscle insulin receptor number and tyrosine kinase activity were unaltered by 48 hr of fasting or 48 hr of fasting and 24 hr of refeeding. Thus, despite the presence of insulin receptors in chicken muscle showing normal coupling to receptor tyrosine kinase activity, nutritional alterations modulate these parameters in a tissue-specific manner in chickens

  17. Evolution of Class I cytokine receptors

    Science.gov (United States)

    Liongue, Clifford; Ward, Alister C

    2007-01-01

    Background The Class I cytokine receptors have a wide range of actions, including a major role in the development and function of immune and blood cells. However, the evolution of the genes encoding them remains poorly understood. To address this we have used bioinformatics to analyze the Class I receptor repertoire in sea squirt (Ciona intestinalis) and zebrafish (Danio rerio). Results Only two Class I receptors were identified in sea squirt, one with homology to the archetypal GP130 receptor, and the other with high conservation with the divergent orphan receptor CLF-3. In contrast, 36 Class I cytokine receptors were present in zebrafish, including representative members for each of the five structural groups found in mammals. This allowed the identification of 27 core receptors belonging to the last common ancestor of teleosts and mammals. Conclusion This study suggests that the majority of diversification of this receptor family occurred after the divergence of urochordates and vertebrates approximately 794 million years ago (MYA), but before the divergence of ray-finned from lobe-finned fishes around 476 MYA. Since then, only relatively limited lineage-specific diversification within the different Class I receptor structural groups has occurred. PMID:17640376

  18. Identification and mechanism of ABA receptor antagonism

    KAUST Repository

    Melcher, Karsten

    2010-08-22

    The phytohormone abscisic acid (ABA) functions through a family of fourteen PYR/PYL receptors, which were identified by resistance to pyrabactin, a synthetic inhibitor of seed germination. ABA activates these receptors to inhibit type 2C protein phosphatases, such as ABI1, yet it remains unclear whether these receptors can be antagonized. Here we demonstrate that pyrabactin is an agonist of PYR1 and PYL1 but is unexpectedly an antagonist of PYL2. Crystal structures of the PYL2-pyrabactin and PYL1-pyrabactin-ABI1 complexes reveal the mechanism responsible for receptor-selective activation and inhibition, which enables us to design mutations that convert PYL1 to a pyrabactin-inhibited receptor and PYL2 to a pyrabactin-activated receptor and to identify new pyrabactin-based ABA receptor agonists. Together, our results establish a new concept of ABA receptor antagonism, illustrate its underlying mechanisms and provide a rational framework for discovering novel ABA receptor ligands. © 2010 Nature America, Inc. All rights reserved.

  19. ABA Receptors: Past, Present and Future

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Jianjun [Harvard University; Yang, Xiaohan [ORNL; Weston, David [ORNL; Chen, Jay [ORNL

    2011-01-01

    Abscisic acid (ABA) is the key plant stress hormone. Consistent with the earlier studies in support of the presence of both membrane- and cytoplasm-localized ABA receptors, recent studies have identified multiple ABA receptors located in various subcellular locations. These include a chloroplast envelope-localized receptor (the H subunit of Chloroplast Mg2+-chelatase/ABA Receptor), two plasma membrane-localized receptors (G-protein Coupled Receptor 2 and GPCR-type G proteins), and one cytosol/nucleus-localized Pyrabactin Resistant (PYR)/PYR-Like (PYL)/Regulatory Component of ABA Receptor 1 (RCAR). Although the downstream molecular events for most of the identified ABA receptors are currently unknown, one of them, PYR/PYL/RACR was found to directly bind and regulate the activity of a long-known central regulator of ABA signaling, the A-group protein phosphatase 2C (PP2C). Together with the Sucrose Non-fermentation Kinase Subfamily 2 (SnRK2s) protein kinases, a central signaling complex (ABA-PYR-PP2Cs-SnRK2s) that is responsible for ABA signal perception and transduction is supported by abundant genetic, physiological, biochemical and structural evidence. The identification of multiple ABA receptors has advanced our understanding of ABA signal perception and transduction while adding an extra layer of complexity.

  20. Amphipathic Benzenes Are Designed Inhibitors of the Estrogen Receptor α/Steroid Receptor Coactivator Interaction

    OpenAIRE

    Gunther, Jillian R.; Moore, Terry W.; Collins, Margaret L.; Katzenellenbogen, John A.

    2008-01-01

    We report here on the design, synthesis and evaluation of small molecule inhibitors of the interaction between a steroid receptor coactivator and estrogen receptor α. These inhibitors are based upon an amphipathic benzene scaffold whose hydrophobic face mimics the leucine-rich α-helical consensus sequence on the steroid receptor coactivators that interacts with a shallow groove on estrogen receptor α. Several of these molecules are among the most potent inhibitors of this interaction describe...

  1. Hypothyroidism Affects D2 Receptor-mediated Breathing without altering D2 Receptor Expression

    OpenAIRE

    Schlenker, Evelyn H.; Rio, Rodrigo Del; Schultz, Harold D.

    2014-01-01

    Bromocriptine depressed ventilation in air and D2 receptor expression in the nucleus tractus solitaries (NTS) in male hypothyroid hamsters. Here we postulated that in age- matched hypothyroid female hamsters, the pattern of D2 receptor modulation of breathing and D2 receptor expression would differ from those reported in hypothyroid males. In females hypothyroidism did not affect D2 receptor protein levels in the NTS, carotid bodies or striatum. Bromocriptine, but not carmoxirole (a periphera...

  2. Hierarchical Phosphorylation of δ-Opioid Receptor Regulates Agonist-induced Receptor Desensitization and Internalization*

    OpenAIRE

    Maestri-El Kouhen, Odile; Wang, Guilin; Solberg, Jonathan; Erickson, Laurie J.; Law, Ping-Yee; Loh, Horace H.

    2000-01-01

    Treatment of HEK293 cells expressing the δ-opioid receptor with agonist [d-Pen2,5]enkephalin (DPDPE) resulted in the rapid phosphorylation of the receptor. We constructed several mutants of the potential phosphorylation sites (Ser/Thr) at the carboxyl tail of the receptor in order to delineate the receptor phosphorylation sites and the agonist-induced desensitization and internalization. The Ser and Thr were substituted to alanine, and the corresponding mutants were transiently and stably exp...

  3. Cigarette smoke increases BLT2 receptor functions in bronchial epithelial cells: in vitro and ex vivo evidence

    Science.gov (United States)

    Pace, Elisabetta; Ferraro, Maria; Vincenzo, Serena Di; Bruno, Andreina; Giarratano, Antonino; Scafidi, Valeria; Lipari, Luana; Benedetto, Denise Valentina Di; Sciarrino, Serafina; Gjomarkaj, Mark

    2013-01-01

    Leukotriene B4 (LTB4) is a neutrophil chemotactic molecule with important involvement in the inflammatory responses of chronic obstructive pulmonary disease (COPD). Airway epithelium is emerging as a regulator of innate immune responses to a variety of insults including cigarette smoke, the major risk factor for COPD. In this study we have explored whether cigarette smoke extracts (CSE) or soluble mediators present in distal lung fluid samples (mini-bronchoalveolar lavages) from smokers alter the expression of the LTB4 receptor 2 (BLT2) and peroxisome proliferator-activated receptor-α (PPAR-α) in bronchial epithelial cells. We also evaluated the effects of CSE on the expression of intercellular adhesion molecule 1 (ICAM-1) and on the binding of signal transducer and activator of transcription 1 (STAT-1) to ICAM-1 promoter as well as the adhesiveness of neutrophils to bronchial epithelial cells. CSE and mini-bronchoalveolar lavages from smokers increased BLT2 and ICAM-1 expression as well as the adhesiveness of neutrophils to bronchial epithelial cells and decreased PPAR-α expression. CSE induced the activation of STAT-1 and its binding to ICAM-1 promoter. These findings suggest that, in bronchial epithelial cells, CSE promote a prevalent induction of pro-inflammatory BLT2 receptors and activate mechanisms leading to increased neutrophil adhesion, a mechanism that contributes to airway neutrophilia and to tissue damage. PMID:23347335

  4. The repertoire of trace amine G-protein-coupled receptors

    DEFF Research Database (Denmark)

    Gloriam, David E.; Bjarnadóttir, Thóra K; Yan, Yi-Lin

    2005-01-01

    eukaryotic species for receptors similar to the mammalian trace amine (TA) receptor subfamily. We identified 18 new receptors in rodents that are orthologous to the previously known TA-receptors. Remarkably, we found 57 receptors (and 40 pseudogenes) of this type in the zebrafish (Danio rerio), while fugu...

  5. One for all: the receptor-associated kinase BAK1.

    NARCIS (Netherlands)

    Chinchilla, D.; Shan, L.; He, P.; Vries, de S.C.; Kemmerling, B.

    2009-01-01

    The plant receptor kinase BAK1/SERK3 has been identified as a partner of ligand-binding leucine-rich repeat receptor kinases, in particular the brassinosteroid receptor BRI1 and the immune receptor FLS2. BAK1 positively regulates BRI1 receptor function via physical interaction and

  6. Atomization of JP-10/B4C gelled slurry fuel

    OpenAIRE

    Guglielmi, John David

    1992-01-01

    The atomization of a gelled boron slurry fuel using two commercially available airblast atomizers was studied at atmospheric pressure in non-reacting flow. The atomization of water was also characterized for comparison. Each atomizer was operated at two different liquid mass flow rates and several air/ fuel ratios. Drop size distribution was measured using a Malvern 2600 HSD Laser Diffraction Particle Sizer, Drop sizes acceptable for use in ramjet combustors could be obtained f...

  7. Session B4 Management for sustainable use — Global climate ...

    African Journals Online (AJOL)

    The IPCC Third Assessment Report confirms that the evidence for global climate change is now stronger than ever. While efforts to minimise climate change are vital, some degree of change is already inevitable. The key questions for rangelands are no longer whether climate change will occur, but how to adapt to it, and if ...

  8. 26 CFR 1.403(b)-4 - Contribution limitations.

    Science.gov (United States)

    2010-04-01

    ... hospice); (2) A section 501(c)(3) organization whose primary activity is the prevention of cruelty to individuals or animals; (3) An adoption agency; or (4) An agency that provides substantial personal services...

  9. The G protein-coupled receptor, class C, group 6, subtype A (GPRC6A) receptor

    DEFF Research Database (Denmark)

    Clemmensen, C; Smajilovic, S; Wellendorph, P

    2014-01-01

    GPRC6A (G protein-coupled receptor, class C, group 6, subtype A) is a class C G protein-coupled receptor, that has been cloned from human, mouse and rat. Several groups have shown that the receptor is activated by a range of basic and small aliphatic L-α-amino acids of which L-arginine, L-lysine...

  10. The substance P/NK-1 receptor system: NK-1 receptor antagonists ...

    Indian Academy of Sciences (India)

    2015-04-27

    Apr 27, 2015 ... The substance P (SP)/neurokinin (NK)-1 receptor system plays an important role in cancer. SP promotes the ... NK-1 receptor may be a promising target in the treatment of cancer; NK-1 receptor antagonists could act as specific ...... mycin, ifosfamide, cisplatin) in MG-63 human osteosarcoma cells, but not in ...

  11. Interaction of epidermal growth factor receptors with the cytoskeleton is related to receptor clustering

    NARCIS (Netherlands)

    van Belzen, N.; Spaargaren, M.; Verkleij, A. J.; Boonstra, J.

    1990-01-01

    Recently it has been established that cytoskeleton-associated epidermal growth factor (EGF) receptors are predominantly of the high-affinity class and that EGF induces a recruitment of low-affinity receptors to the cytoskeleton. The nature of this EGF-induced receptor-cytoskeleton interaction,

  12. Posttransplant chimeric antigen receptor therapy.

    Science.gov (United States)

    Smith, Melody; Zakrzewski, Johannes; James, Scott; Sadelain, Michel

    2018-03-08

    Therapeutic T-cell engineering is emerging as a powerful approach to treat refractory hematological malignancies. Its most successful embodiment to date is based on the use of second-generation chimeric antigen receptors (CARs) targeting CD19, a cell surface molecule found in most B-cell leukemias and lymphomas. Remarkable complete remissions have been obtained with autologous T cells expressing CD19 CARs in patients with relapsed, chemo-refractory B-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma. Allogeneic CAR T cells may also be harnessed to treat relapse after allogeneic hematopoietic stem cell transplantation. However, the use of donor T cells poses unique challenges owing to potential alloreactivity. We review different approaches to mitigate the risk of causing or aggravating graft-versus-host disease (GVHD), including CAR therapies based on donor leukocyte infusion, virus-specific T cells, T-cell receptor-deficient T cells, lymphoid progenitor cells, and regulatory T cells. Advances in CAR design, T-cell selection and gene editing are poised to enable the safe use of allogeneic CAR T cells without incurring GVHD. © 2018 by The American Society of Hematology.

  13. Microarray-Based Determination of Estrogen Receptor, Progesterone Receptor, and HER2 Receptor Status in Breast Cancer

    NARCIS (Netherlands)

    Roepman, Paul; Horlings, Hugo M.; Krijgsman, Oscar; Kok, Marleen; Bueno-de-Mesquita, Jolien M.; Bender, Richard; Linn, Sabine C.; Glas, Annuska M.; van de Vijver, Marc J.

    2009-01-01

    Purpose: The level of estrogen receptor (ER), progesterone receptor (PR), and HER2 aids in the determination of prognosis and treatment of breast cancer. Immunohistochemistry is currently the predominant method for assessment, but differences in methods and interpretation can substantially affect

  14. The lactate receptor, G-protein-coupled receptor 81/hydroxycarboxylic acid receptor 1

    DEFF Research Database (Denmark)

    Morland, Cecilie; Lauritzen, Knut Huso; Puchades, Maja

    2015-01-01

    , and schizophrenia and in the deposition of phosphorylated tau protein in Alzheimer's disease. HCAR1 could serve to ameliorate these conditions and might also act through downstream mechanisms other than cAMP. Lactate exits cells through monocarboxylate transporters in an equilibrating manner and through astrocyte...... anion channels activated by depolarization. In addition to locally produced lactate, lactate produced by exercising muscle as well as exogenous HCAR1 agonists, e.g., from fruits and berries, might activate the receptor on cerebral blood vessels and brain cells....

  15. Effects of Co, Ni, and Cr addition on microstructure and magnetic properties of amorphous and nanocrystalline Fe86−xMxZr7Nb2Cu1B4 (M = Co, Ni, CoCr, and Cr, x = 0 or 6 alloys

    Directory of Open Access Journals (Sweden)

    Łukiewska Agnieszka

    2015-03-01

    Full Text Available Mössbauer spectra and thermomagnetic curves for the Fe86−xMxZr7Nb2Cu1B4 (M = Co, Ni, CoCr, and Cr, x = 0 or 6 alloys in the as-quenched state and after the accumulative annealing in the temperature range 600–800 K for 10 min are investigated. The parent Fe86Zr7Nb2Cu1B4 amorphous alloy is paramagnetic at room temperature, and substitution of 6 at.% of Fe by Co, Ni, and CoCr changes the magnetic structure – the alloys become ferromagnetic, whereas replacing 6 at.% of Fe with Cr preserves the paramagnetic state. After the heat treatment at 600 K, the decrease of the average hyperfine field induction, as compared to the as-quenched state, is observed due to the invar effect. After this annealing, the Curie temperature for all investigated alloys decreases. The accumulative annealing up to 800 K leads to the partial crystallization; α-Fe or α-FeCo grains with diameters in the range of 12–30 nm in the residual amorphous matrix appear.

  16. A bioluminescence resonance energy transfer 2 (BRET2) assay for monitoring seven transmembrane receptor and insulin receptor crosstalk

    DEFF Research Database (Denmark)

    Sanni, Samra Joke; Kulahin, Nikolaj; Jorgensen, Rasmus

    2017-01-01

    The angiotensin AT1 receptor is a seven transmembrane (7TM) receptor, which mediates the regulation of blood pressure. Activation of angiotensin AT1 receptor may lead to impaired insulin signaling indicating crosstalk between angiotensin AT1 receptor and insulin receptor signaling pathways. To el...

  17. Cannabinoid 2 Receptor- and Beta Arrestin 2-Dependent Upregulation of Serotonin 2A Receptors

    OpenAIRE

    Franklin, J.M.; Vasiljevik, T.; Prisinzano, T.E.; Carrasco, G.A.

    2012-01-01

    Recent evidence suggests that cannabinoid receptor agonists may regulate serotonin 2A (5-HT2A) receptor neurotransmission in the brain, although no molecular mechanism has been identified. Here, we present experimental evidence that sustained treatment with a non-selective cannabinoid agonist (CP 55,940) or selective CB2 receptor agonists (JWH 133 or GP 1a) upregulate 5-HT2A receptors in a neuronal cell line. Furthermore, this cannabinoid receptor agonist-induced upregulation of 5-HT2A recept...

  18. Identifying the receptor subtype selectivity of retinoid X and retinoic acid receptors via quantum mechanics.

    Science.gov (United States)

    Tsuji, Motonori; Shudo, Koichi; Kagechika, Hiroyuki

    2017-03-01

    Understanding and identifying the receptor subtype selectivity of a ligand is an important issue in the field of drug discovery. Using a combination of classical molecular mechanics and quantum mechanical calculations, this report assesses the receptor subtype selectivity for the human retinoid X receptor (hRXR) and retinoic acid receptor (hRAR) ligand-binding domains (LBDs) complexed with retinoid ligands. The calculated energies show good correlation with the experimentally reported binding affinities. The technique proposed here is a promising method as it reveals the origin of the receptor subtype selectivity of selective ligands.

  19. In vivo studies of opiate receptors

    International Nuclear Information System (INIS)

    Frost, J.J.; Dannals, R.F.; Duelfer, T.; Burns, H.D.; Ravert, H.T.; Langstroem, B.; Balasubramanian, V.; Wagner, H.N. Jr.

    1984-01-01

    To study opiate receptors noninvasively in vivo using positron emission tomography, techniques for preferentially labeling opiate receptors in vivo can be used. The rate at which receptor-bound ligand clears from the brain in vivo can be predicted by measuring the equilibrium dissociation constant (KD) at 37 degrees C in the presence of 100 mM sodium chloride and 100 microM guanyl-5'-imidodiphosphate, the drug distribution coefficient, and the molecular weight. A suitable ligand for labeling opiate receptors in vivo is diprenorphine, which binds to mu, delta, and kappa receptors with approximately equal affinity in vitro. However, in vivo diprenorphine may bind predominantly to one opiate receptor subtype, possibly the mu receptor. To predict the affinity for binding to the opiate receptor, a Hansch correlation was determined between the 50% inhibitory concentration for a series of halogen-substituted fentanyl analogs and electronic, lipophilic, and steric parameters. Radiochemical methods for the synthesis of carbon-11-labeled diprenorphine and lofentanil are presented

  20. In vivo studies of opiate receptors

    Energy Technology Data Exchange (ETDEWEB)

    Frost, J.J.; Dannals, R.F.; Duelfer, T.; Burns, H.D.; Ravert, H.T.; Langstroem, B.; Balasubramanian, V.; Wagner, H.N. Jr.

    1984-01-01

    To study opiate receptors noninvasively in vivo using positron emission tomography, techniques for preferentially labeling opiate receptors in vivo can be used. The rate at which receptor-bound ligand clears from the brain in vivo can be predicted by measuring the equilibrium dissociation constant (KD) at 37 degrees C in the presence of 100 mM sodium chloride and 100 microM guanyl-5'-imidodiphosphate, the drug distribution coefficient, and the molecular weight. A suitable ligand for labeling opiate receptors in vivo is diprenorphine, which binds to mu, delta, and kappa receptors with approximately equal affinity in vitro. However, in vivo diprenorphine may bind predominantly to one opiate receptor subtype, possibly the mu receptor. To predict the affinity for binding to the opiate receptor, a Hansch correlation was determined between the 50% inhibitory concentration for a series of halogen-substituted fentanyl analogs and electronic, lipophilic, and steric parameters. Radiochemical methods for the synthesis of carbon-11-labeled diprenorphine and lofentanil are presented.