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Sample records for triggers aryl hydrocarbon

  1. Antioxidant Functions of the Aryl Hydrocarbon Receptor

    Directory of Open Access Journals (Sweden)

    Cornelia Dietrich

    2016-01-01

    Full Text Available The aryl hydrocarbon receptor (AhR is a transcription factor belonging to the basic helix-loop-helix/PER-ARNT-SIM family. It is activated by a variety of ligands, such as environmental contaminants like polycyclic aromatic hydrocarbons or dioxins, but also by naturally occurring compounds and endogenous ligands. Binding of the ligand leads to dimerization of the AhR with aryl hydrocarbon receptor nuclear translocator (ARNT and transcriptional activation of several xenobiotic phase I and phase II metabolizing enzymes. It is generally accepted that the toxic responses of polycyclic aromatic hydrocarbons, dioxins, and structurally related compounds are mediated by activation of the AhR. A multitude of studies indicate that the AhR operates beyond xenobiotic metabolism and exerts pleiotropic functions. Increasing evidence points to a protective role of the AhR against carcinogenesis and oxidative stress. Herein, I will highlight data demonstrating a causal role of the AhR in the antioxidant response and present novel findings on potential AhR-mediated antioxidative mechanisms.

  2. Aryl-Hydrocarbon Receptor Based Antiestrogenicity of Diindolylmethane Analogs

    National Research Council Canada - National Science Library

    Lee, Jeong-Eun

    2001-01-01

    .... In this study, we have investigated the aryl hydrocarbon receptor (AhR) agonist activity and inhibitory AhR-estrogen receptor crosstalk induced by the following methyl-substituted DIMs: 1,11-dimethyl-; 2,2'- dimethyl-; 5,5' -dimethyl; 6,6' -dimethyl...

  3. Role of the Aryl Hydrocarbon Receptor in Colon Neoplasia

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Guofeng, E-mail: gxie@medicine.umaryland.edu; Raufman, Jean-Pierre [Division of Gastroenterology and Hepatology, Veterans Administration Maryland Health Care System, University of Maryland School of Medicine, Baltimore, MD 21201 (United States)

    2015-07-31

    For both men and women, colorectal cancer (CRC) is the second leading cause of cancer death in the United States, primarily as a consequence of limited therapies for metastatic disease. The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor with diverse functions in detoxification of xenobiotics, inflammatory responses, and tissue homeostasis. Emerging evidence indicates that AhR also plays an important role in regulating intestinal cell proliferation and tumorigenesis. Here, we review both the pro- and anti-carcinogenic properties of AhR signaling and its potential role as a therapeutic target in CRC.

  4. Aryl hydrocarbon mono-oxygenase activity in human lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Griffin, G.D.; Schuresko, D.D.

    1981-06-01

    Aryl hydrocarbon mono-oxygenase (AHM), an enzyme of key importance in metabolism of xenobiotic chemicals such as polynuclear aromatic hydrocarbons (PNA), is present in human lymphocytes. Studies investing the relation of activity of AHM in human lymphocytes to parameters such as disease state, PNA exposure, in vitro mitogen stimulation, etc. have been summarized in this report. Some studies have demonstrated increased AHM activity in lymphocytes from cigarette smokers (compared to nonsmokers), and in lung cancer patients when compared to appropriate control groups. These observations are confused by extreme variability in human lymphocyte AHM activities, such variability arising from factors such as genetic variation in AHM activity, variation in in vitro culture conditions which affect AHM activity, and the problematical relationship of common AHM assays to actual PNA metabolism taking place in lymphocytes. If some of the foregoing problems can be adequately addressed, lymphocyte AHM activity could hold the promise of being a useful biomarker system for human PNA exposure.

  5. Cyprodinil as an activator of aryl hydrocarbon receptor

    International Nuclear Information System (INIS)

    Fang, Chien-Chung; Chen, Fei-Yun; Chen, Chang-Rong; Liu, Chien-Chiang; Wong, Liang-Chi; Liu, Yi-Wen; Su, Jyan-Gwo Joseph

    2013-01-01

    Highlights: ► Cyprodinil activated the aryl hydrocarbon receptor (AHR). ► Cyprodinil induced nuclear translocation of the AHR, and the expression of CYP1A1. ► Cyprodinil enhanced dexamethasone-induced gene expression. ► Cyprodinil phosphorylated ERK, indicating its deregulation of ERK activity. -- Abstract: Cyprodinil is a pyrimidinamine fungicide, used worldwide by agriculture. It is used to protect fruit plants and vegetables from a wide range of pathogens. Benzo[a]pyrene (BaP) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are toxic environmental pollutants and are prototypes of aryl hydrocarbon receptor (AHR) ligands. Although the structure of cyprodinil distinctly differs from those of BaP and TCDD, our results show that cyprodinil induced nuclear translocation of the AHR, and induced the transcriptional activity of aryl hydrocarbon response element (AHRE). Cyprodinil induced the expression of cytochrome P450 (CYP) 1A1, a well-known AHR-targeted gene, in ovarian granulosa cells, HO23, and hepatoma cells, Hepa-1c1c7. Its induction did not appear in AHR signal-deficient cells, and was blocked by the AHR antagonist, CH-223191. Cyprodinil decreased AHR expression in HO23 cells, resulting in CYP1A1 expression decreasing after it peaked at 9 h of treatment in HO23 cells. Dexamethasone is a synthetic agonist of glucocorticoids. Cyprodinil enhanced dexamethasone-induced gene expression, and conversely, its induction of CYP1A1 expression was decreased by dexamethasone in HO23 cells, indicating its induction of crosstalk between the AHR and glucocorticoid receptor and its role as a potential endocrine disrupter. In addition to BaP, TCDD, and an AHR agonist, β-NF, cyprodinil also phosphorylated extracellular signal-regulated kinase (ERK) in HO23 and Hepa-1c1c7 cells, indicating its deregulation of ERK activity. In summary, our results demonstrate that cyprodinil, similar to BaP, acts as an AHR activator, a potential endocrine disrupter, and an ERK disrupter

  6. Cyprodinil as an activator of aryl hydrocarbon receptor.

    Science.gov (United States)

    Fang, Chien-Chung; Chen, Fei-Yun; Chen, Chang-Rong; Liu, Chien-Chiang; Wong, Liang-Chi; Liu, Yi-Wen; Su, Jyan-Gwo Joseph

    2013-02-08

    Cyprodinil is a pyrimidinamine fungicide, used worldwide by agriculture. It is used to protect fruit plants and vegetables from a wide range of pathogens. Benzo[a]pyrene (BaP) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are toxic environmental pollutants and are prototypes of aryl hydrocarbon receptor (AHR) ligands. Although the structure of cyprodinil distinctly differs from those of BaP and TCDD, our results show that cyprodinil induced nuclear translocation of the AHR, and induced the transcriptional activity of aryl hydrocarbon response element (AHRE). Cyprodinil induced the expression of cytochrome P450 (CYP) 1A1, a well-known AHR-targeted gene, in ovarian granulosa cells, HO23, and hepatoma cells, Hepa-1c1c7. Its induction did not appear in AHR signal-deficient cells, and was blocked by the AHR antagonist, CH-223191. Cyprodinil decreased AHR expression in HO23 cells, resulting in CYP1A1 expression decreasing after it peaked at 9h of treatment in HO23 cells. Dexamethasone is a synthetic agonist of glucocorticoids. Cyprodinil enhanced dexamethasone-induced gene expression, and conversely, its induction of CYP1A1 expression was decreased by dexamethasone in HO23 cells, indicating its induction of crosstalk between the AHR and glucocorticoid receptor and its role as a potential endocrine disrupter. In addition to BaP, TCDD, and an AHR agonist, β-NF, cyprodinil also phosphorylated extracellular signal-regulated kinase (ERK) in HO23 and Hepa-1c1c7 cells, indicating its deregulation of ERK activity. In summary, our results demonstrate that cyprodinil, similar to BaP, acts as an AHR activator, a potential endocrine disrupter, and an ERK disrupter. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  7. A Molecular Model for Repression of BRCA-1 Transcription by the Aryl Hydrocarbon Receptor

    National Research Council Canada - National Science Library

    Romagnolo, Donato

    2003-01-01

    ...) is mediated by the aryl hydrocarbon receptor (AhR). The scope of the project is to examine whether or not the activated AhR alters BRCA-1 transcription through binding to several xenobiotic responsive elements (XRE...

  8. Evodiamine as a novel antagonist of aryl hydrocarbon receptor

    International Nuclear Information System (INIS)

    Yu, Hui; Tu, Yongjiu; Zhang, Chun; Fan, Xia; Wang, Xi; Wang, Zhanli; Liang, Huaping

    2010-01-01

    Research highlights: → Evodiamine interacted with the AhR. → Evodiamine inhibited the specific binding of [ 3 H]-TCDD to the AhR. → Evodiamine acts as an antagonist of the AhR. -- Abstract: Evodiamine, the major bioactive alkaloid isolated from Wu-Chu-Yu, has been shown to interact with a wide variety of proteins and modify their expression and activities. In this study, we investigated the interaction between evodiamine and the aryl hydrocarbon receptor (AhR). Molecular modeling results revealed that evodiamine directly interacted with the AhR. Cytosolic receptor binding assay also provided the evidence that evodiamine could interact with the AhR with the K i value of 28.4 ± 4.9 nM. In addition, we observed that evodiamine suppressed the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced nuclear translocation of the AhR and the expression of CYP1A1 dose-dependently. These results suggested that evodiamine was able to bind to the AhR as ligand and exhibit antagonistic effects.

  9. Regulation of Innate Lymphoid Cells by Aryl Hydrocarbon Receptor

    Directory of Open Access Journals (Sweden)

    Shiyang Li

    2018-01-01

    Full Text Available With striking similarity to their adaptive T helper cell counterparts, innate lymphoid cells (ILCs represent an emerging family of cell types that express signature transcription factors, including T-bet+ Eomes+ natural killer cells, T-bet+ Eomes− group 1 ILCs, GATA3+ group 2 ILCs, RORγt+ group 3 ILCs, and newly identified Id3+ regulatory ILC. ILCs are abundantly present in barrier tissues of the host (e.g., the lung, gut, and skin at the interface of host–environment interactions. Active research has been conducted to elucidate molecular mechanisms underlying the development and function of ILCs. The aryl hydrocarbon receptor (Ahr is a ligand-dependent transcription factor, best known to mediate the effects of xenobiotic environmental toxins and endogenous microbial and dietary metabolites. Here, we review recent progresses regarding Ahr function in ILCs. We focus on the Ahr-mediated cross talk between ILCs and other immune/non-immune cells in host tissues especially in the gut. We discuss the molecular mechanisms of the action of Ahr expression and activity in regulation of ILCs in immunity and inflammation, and the interaction between Ahr and other pathways/transcription factors in ILC development and function with their implication in disease.

  10. Enantiospecific effects of ketoconazole on aryl hydrocarbon receptor.

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    Aneta Novotna

    Full Text Available Azole antifungal ketoconazole (KET was demonstrated to activate aryl hydrocarbon receptor (AhR. Since clinically used KET is a racemic mixture of two cis-enantiomers (2R,4S-(+-KET and (2S,4R-(--KET, we examined the effects of KET enantiomers on AhR signaling pathway. (+-KET dose-dependently activated AhR in human gene reporter cell line AZ-AHR, and displayed 5-20× higher agonist activity (efficacy, as compared to (--KET; both enantiomers were AhR antagonists with equal potency (IC50. Consistently, (+-KET strongly induced CYP1A1 mRNA and protein in human HepG2 cells, while (--KET exerted less than 10% of (+-KET activity. In primary human hepatocytes, both enantiomers preferentially induced CYP1A2 over CYP1A1 mRNA and protein, and the potency of (+-KET was slightly higher as compared to (--KET. Ligand binding assay with guinea pig liver cytosols revealed that both (+-KET and (--KET are weak ligands of AhR that displaced [3H]-TCDD with comparable potency. Similarly, both enantiomers weakly transformed AhR to DNA-binding form with similar potency, as showed by EMSA, in guinea pig liver cytosolic extracts and nuclear extracts from mouse Hepa-1 cells. We also examined effects of KET on glucocorticoid receptor (GR, a regulator of AhR activity. Both KET enantiomers antagonized GR with similar potency, as revealed by gene reporter assay in AZ-GR cell line and down-regulation of tyrosine aminotransferase mRNA in human hepatocytes. Finally, we demonstrate enantiospecific antifungal activities of KET enantiomers in six Candida spp. strains. In conclusion, the significance of current study is providing the first evidence of enatiospecific effects of cis-enantiomers of ketoconazole on AhR-CYP1A pathway.

  11. Oculomotor deficits in aryl hydrocarbon receptor null mouse.

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    Aline Chevallier

    Full Text Available The Aryl hydrocarbon Receptor or AhR, a ligand-activated transcription factor, is known to mediate the toxic and carcinogenic effects of various environmental pollutants such as 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD. Recent studies in Caenorhabditis elegans and Drosophila melanogaster show that the orthologs of the AhR are expressed exclusively in certain types of neurons and are implicated in the development and the homeostasis of the central nervous system. While physiological roles of the AhR were demonstrated in the mammalian heart, liver and gametogenesis, its ontogenic expression and putative neural functions remain elusive. Here, we report that the constitutive absence of the AhR in adult mice (AhR-/- leads to abnormal eye movements in the form of a spontaneous pendular horizontal nystagmus. To determine if the nystagmus is of vestibular, visual, or cerebellar origin, gaze stabilizing reflexes, namely vestibulo-ocular and optokinetic reflexes (VOR and OKR, were investigated. The OKR is less effective in the AhR-/- mice suggesting a deficit in the visuo-motor circuitry, while the VOR is mildly affected. Furthermore, the AhR is expressed in the retinal ganglion cells during the development, however electroretinograms revealed no impairment of retinal cell function. The structure of the cerebellum of the AhR-/- mice is normal which is compatible with the preserved VOR adaptation, a plastic process dependent on cerebellar integrity. Finally, intoxication with TCDD of control adults did not lead to any abnormality of the oculomotor control. These results demonstrate that the absence of the AhR leads to acquired central nervous system deficits in the adults. Given the many common features between both AhR mouse and human infantile nystagmus syndromes, the AhR-/- mice might give insights into the developmental mechanisms which lead to congenital eye disorders.

  12. Aryl hydrocarbon receptor-mediated activity of mutagenic polycyclic aromatic hydrocarbons determined using in vitro reporter gene assay

    Czech Academy of Sciences Publication Activity Database

    Machala, M.; Vondráček, Jan; Bláha, L.; Ciganek, M.; Neča, J.

    2001-01-01

    Roč. 497, 1-2 (2001), s. 49-62 ISSN 1383-5718 R&D Projects: GA MZe QC0194; GA ČR GA525/00/D101 Institutional research plan: CEZ:AV0Z5004920 Keywords : PAHs * aryl hydrocarbon receptor-mediated activity * mutagenicity Subject RIV: BO - Biophysics Impact factor: 1.624, year: 2001

  13. Smoke carcinogens cause bone loss through the aryl hydrocarbon receptor and induction of CYP1 enzymes

    Science.gov (United States)

    Smoking is a major risk factor for osteoporosis and fracture. Here, we show that smoke toxins and environmental chemicals such as benzo[a]pyrene (BaP), 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD), and 3-methyl cholanthrene, which are well known aryl hydrocarbon receptor (AHR) agonists, induce osteocla...

  14. Aryl hydrocarbon receptor expression by macrophages and lymphocytes within infiltrates in BK polyomavirus associated nephropathy

    NARCIS (Netherlands)

    Bouatou, Yassine; Stokman, Geurt; Claessen, Nike; Roelofs, Joris J. T. H.; Bemelman, Frédérike; Kers, Jesper; Florquin, Sandrine

    2018-01-01

    BK virus nephropathy (BKPyVN) is a major complication after renal transplantation. Little is known about the intra renal immune response during BKPyVN. The role of macrophages remains elusive. The activation of aryl hydrocarbon receptor (AHR) - a transcription factor involved in drug metabolism -

  15. 3-methylcholanthrene induces differential recruitment of aryl hydrocarbon receptor to human promoters

    DEFF Research Database (Denmark)

    Pansoy, Andrea; Ahmed, Shaimaa; Valen, Eivind

    2010-01-01

    The aryl hydrocarbon receptor (AHR) is a ligand-activated protein that mediates the toxic actions of polycyclic aromatic and halogenated compounds. Identifying genes directly regulated by AHR is important in understanding the pathways regulated by this receptor. Here we used chromatin immunopreci...

  16. Dioxin increases the interaction between aryl hydrocarbon receptor and estrogen receptor alpha at human promoters

    DEFF Research Database (Denmark)

    Ahmed, Shaaima; Valen, Eivind; Sandelin, Albin Gustav

    2009-01-01

    Recent studies have shown that activated aryl hydrocarbon receptor (AHR) induced the recruitment of estrogen receptor- (ER ) to AHR-regulated genes and that AHR is recruited to ER -regulated genes. However, these findings were limited to a small number of well-characterized AHR- or ER -responsive...

  17. Characterization of an Aryl Hydrocarbon Receptor from a Cetacean: An Approach for Assessing Contaminant Susceptibility in Protected Species

    National Research Council Canada - National Science Library

    Jensen, Brenda

    2000-01-01

    ...) and related HAH cause toxicity via activation of the aryl hydrocarbon receptor (AHR). Differences in AHR structure and function are known to contribute to species-specific differences in susceptibility to HAH toxicity...

  18. In vitro function of the aryl hydrocarbon receptor predicts in vivo sensitivity of oviparous vertebrates to dioxin-like compounds

    Science.gov (United States)

    Differences in sensitivity to dioxin-like compounds (DLCs) among species and taxa presents a major challenge to ecological risk assessments. Activation of the aryl hydrocarbon receptor (AHR) regulates adverse effects associated with exposure to DLCs in vertebrates. Prior investig...

  19. Expression of Aryl Hydrocarbon Receptor in Human Placentas and Fetal Tissues

    OpenAIRE

    Jiang, Yi-zhou; Wang, Kai; Fang, Roy; Zheng, Jing

    2010-01-01

    The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, mediates many biological processes, including fetal development. In this study, we examined AhR protein expression in human placentas from normal (N) and severe preeclamptic (sPE) pregnancies, as well as human fetal tissues from the second trimester of pregnancy, using immunohistochemistry and/or Western blot analysis. In the placentas, the AhR immunoreactivity was present primarily in syncytiotrophoblasts. The AhR ...

  20. Altered subcellular localization of heat shock protein 90 is associated with impaired expression of the aryl hydrocarbon receptor pathway in dogs.

    Directory of Open Access Journals (Sweden)

    Frank G van Steenbeek

    Full Text Available 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 protein (AIP and aryl hydrocarbon receptor nuclear translocator (ARNT. The resulting intrahepatic portosystemic shunts (IHPSS are frequently diagnosed in specific dog breeds, such as the Irish wolfhound. We compared the expression of components of the AHR pathway in healthy Irish wolfhounds and dogs with IHPSS. To this end, we analyzed the mRNA expression in the liver of AHR,AIP, ARNT, and other genes involved in this pathway, namely, those for aryl hydrocarbon receptor nuclear translocator 2 (ARNT2, hypoxia inducible factor 1alpha (HIF1A, heat shock protein 90AA1 (HSP90AA1, cytochromes P450 (CYP1A1, CYP1A2, and CYP1B1, vascular endothelial growth factor A (VEGFA, nitric oxide synthesase 3 (NOS3, and endothelin (EDN1. The observed low expression of AHR mRNA in the Irish wolfhounds is in associated with a LINE-1 insertion in intron 2, for which these dogs were homozygous. Down regulation in Irish wolfhounds was observed for AIP, ARNT2, CYP1A2, CYP1B1 and HSP90AA1 expression, whereas the expression of HIF1A was increased. Immunohistochemistry revealed lower levels of AHR, HIF1A, and VEGFA protein in the nucleus and lower levels of ARNT and HSP90AA1 protein in the cytoplasm of the liver cells of Irish wolfhounds. The impaired expression of HSP90AA1 could trigger the observed differences in mRNA and protein levels and therefore explain the link between two very different functions of AHR: regulation of the closure of the ductus venosus and the response to toxins.

  1. Altered subcellular localization of heat shock protein 90 is associated with impaired expression of the aryl hydrocarbon receptor pathway in dogs.

    Science.gov (United States)

    van Steenbeek, Frank G; Spee, Bart; Penning, Louis C; Kummeling, Anne; van Gils, Ingrid H M; Grinwis, Guy C M; Van Leenen, Dik; Holstege, Frank C P; Vos-Loohuis, Manon; Rothuizen, Jan; Leegwater, Peter A J

    2013-01-01

    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 protein (AIP) and aryl hydrocarbon receptor nuclear translocator (ARNT). The resulting intrahepatic portosystemic shunts (IHPSS) are frequently diagnosed in specific dog breeds, such as the Irish wolfhound. We compared the expression of components of the AHR pathway in healthy Irish wolfhounds and dogs with IHPSS. To this end, we analyzed the mRNA expression in the liver of AHR,AIP, ARNT, and other genes involved in this pathway, namely, those for aryl hydrocarbon receptor nuclear translocator 2 (ARNT2), hypoxia inducible factor 1alpha (HIF1A), heat shock protein 90AA1 (HSP90AA1), cytochromes P450 (CYP1A1, CYP1A2, and CYP1B1), vascular endothelial growth factor A (VEGFA), nitric oxide synthesase 3 (NOS3), and endothelin (EDN1). The observed low expression of AHR mRNA in the Irish wolfhounds is in associated with a LINE-1 insertion in intron 2, for which these dogs were homozygous. Down regulation in Irish wolfhounds was observed for AIP, ARNT2, CYP1A2, CYP1B1 and HSP90AA1 expression, whereas the expression of HIF1A was increased. Immunohistochemistry revealed lower levels of AHR, HIF1A, and VEGFA protein in the nucleus and lower levels of ARNT and HSP90AA1 protein in the cytoplasm of the liver cells of Irish wolfhounds. The impaired expression of HSP90AA1 could trigger the observed differences in mRNA and protein levels and therefore explain the link between two very different functions of AHR: regulation of the closure of the ductus venosus and the response to toxins.

  2. The aryl hydrocarbon receptor-dependent deregulation of cell cycle control induced by polycyclic aromatic hydrocarbons in rat liver epithelial cells

    Czech Academy of Sciences Publication Activity Database

    Andrysík, Zdeněk; Vondráček, Jan; Machala, M.; Krčmář, P.; Šindlerová, Lenka; Kranz, A.; Weiss, C.; Faust, D.; Kozubík, Alois; Dietrich, C.

    2007-01-01

    Roč. 615, č. 1-2 (2007), s. 87-97 ISSN 0027-5107 R&D Projects: GA AV ČR(CZ) KJB6004407 Institutional research plan: CEZ:AV0Z50040702 Keywords : aryl hydrocarbon receptor * contact inhibition * polycyclic aromatic hydrocarbons Subject RIV: BO - Biophysics Impact factor: 4.159, year: 2007

  3. The Aryl Hydrocarbon Receptor Nuclear Translocator (ARNT/HIF-1β is Influenced by Hypoxia and Hypoxia-Mimetics

    Directory of Open Access Journals (Sweden)

    Matthias Wolff

    2013-09-01

    Full Text Available Background: The Aryl Hydrocarbon Receptor Nuclear Translocator (ARNT, HIF-1β is a member of the basic-Helix-Loop-Helix PER/ARNT/SIM (bHLH/PAS protein family and a vital transcriptional regulator regarding development and physiological adaptation processes. ARNT is discussed to be linked with cancer, and other diseases. ARNT is known to be translocated into the cell nucleus, where accumulation of the protein takes place. ARNT is a heterodimerisation partner of the xenobiotic ligand activated Aryl Hydrocarbon Receptor (AhR, the Single Minded proteins (SIM, the cardiovascular helix-loop-helix factor 1 and the Hypoxia Inducible Factor proteins (HIF-α. ARNT is obligatory for HIF-1, HIF-2 and HIF-3 binding to DNA. Whereas degradation of the HIF-α subunits is suppressed by hypoxia, ARNT is generally regarded as constitutively expressed in excess within the cell, and stabilisation is commonly thought to be oxygen-independent. However, we provide evidence that the regulation of ARNT is far more complex. The aim of our study was to reevaluate the regulation of ARNT expression. Methods: We examined cell lines of different origin like MCF-7 and T47D (human breast cancer, HeLa (human cervix carcinoma, Hep3B and HepG2 (human hepatoma, Kelly (human neuroblastoma, REPC (human kidney and Cos7 (primary primate kidney cells. We used immunoblot analysis, densitometry, RT-PCR and transient transfection. Results and Conclusion: Our results show that ARNT protein levels are influenced by hypoxia and hypoxia mimetics such as cobalt(II-chloride (CoCl2 and dimethyloxalylglycine (DMOG in a cell line specific manner. We demonstrate that this effect might be triggered by HIF-1α which plays an important role in the process of stabilizing ARNT in hypoxia.

  4. Evidence of the aryl hydrocarbon receptor in chemosynthetic mussels from the Gulf of Mexico

    International Nuclear Information System (INIS)

    Willett, K.; Thomsen, J.; Wilson, C.; McDonald, S.; Safe, S.

    1995-01-01

    The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that controls expression of various genes including cytochrome P450. Polynuclear aromatic and halogenated aromatic hydrocarbons are agonists for the AhR in fish and mammalian species. Previously, a homologous AhR has not been identified in marine invertebrate species. Chemosynthetic mussels were collected from gas and petroleum seeps in the Gulf of Mexico to investigate the presence of the AhR and the induction of the cytochrome P450 system. Aryl hydrocarbon hydroxylase and glutathione S-transferase activities in the gill and hepatopancreas were elevated in the petroleum seep mussels relative to those from the gas seep. A nuclear AhR in the hepatopancreas was detected in both mussel populations after treatment with [ 3 H]-tetrachlorodibenzo-p-dioxin (tcdd) followed by sucrose density gradient analysis. Gel mobility shift assays using a labeled dioxin responsive element (DRE) oligonucleotide and tcdd-transformed mussel cytosol showed a retarded band which could be competed with excess unlabeled DRE. Results from gel shifts indicated specific binding of the tcdd-mussel AhR complex to its responsible element. Finally, PCR primers designed to amplify a 700 base pair region of the human AhR detected AhR mRNA in both mussel populations. The sequence of this PCR product is being determined. The presence of the AhR in marine invertebrates has important implications in the evolutionary age of the AhR

  5. The aryl hydrocarbon receptor and glucocorticoid receptor interact to activate human metallothionein 2A

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Shoko, E-mail: satosho@rs.tus.ac.jp [Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555 (Japan); Shirakawa, Hitoshi, E-mail: shirakah@m.tohoku.ac.jp [Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555 (Japan); Tomita, Shuhei, E-mail: tomita@med.tottori-u.ac.jp [Division of Molecular Pharmacology, Department of Pathophysiological and Therapeutic Science, Yonago 683-8503 (Japan); Tohkin, Masahiro, E-mail: tohkin@phar.nagoya-cu.ac.jp [Department of Medical Safety Science, Graduate School of Pharmaceutical Science, Nagoya City University, Nagoya 267-8603 (Japan); Gonzalez, Frank J., E-mail: gonzalef@mail.nih.gov [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Komai, Michio, E-mail: mkomai@m.tohoku.ac.jp [Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555 (Japan)

    2013-11-15

    Although the aryl hydrocarbon receptor (AHR) and glucocorticoid receptor (GR) play essential roles in mammalian development, stress responses, and other physiological events, crosstalk between these receptors has been the subject of much debate. Metallothioneins are classic glucocorticoid-inducible genes that were reported to increase upon treatment with AHR agonists in rodent tissues and cultured human cells. In this study, the mechanism of human metallothionein 2A (MT2A) gene transcription activation by AHR was investigated. Cotreatment with 3-methylcholanthrene and dexamethasone, agonists of AHR and GR respectively, synergistically increased MT2A mRNA levels in HepG2 cells. MT2A induction was suppressed by RNA interference against AHR or GR. Coimmunoprecipitation experiments revealed a physical interaction between AHR and GR proteins. Moreover, chromatin immunoprecipitation assays indicated that AHR was recruited to the glucocorticoid response element in the MT2A promoter. Thus, we provide a novel mechanism whereby AHR modulates expression of human MT2A via the glucocorticoid response element and protein–protein interactions with GR. - Highlights: • Aryl hydrocarbon receptor forms a complex with glucocorticoid receptor in cells. • Human metallothionein gene is regulated by the AHR and GR interaction. • AHR–GR complex binds to glucocorticoid response element in metallothionein gene. • We demonstrated a novel transcriptional mechanism via AHR and GR interaction.

  6. The aryl hydrocarbon receptor and glucocorticoid receptor interact to activate human metallothionein 2A

    International Nuclear Information System (INIS)

    Sato, Shoko; Shirakawa, Hitoshi; Tomita, Shuhei; Tohkin, Masahiro; Gonzalez, Frank J.; Komai, Michio

    2013-01-01

    Although the aryl hydrocarbon receptor (AHR) and glucocorticoid receptor (GR) play essential roles in mammalian development, stress responses, and other physiological events, crosstalk between these receptors has been the subject of much debate. Metallothioneins are classic glucocorticoid-inducible genes that were reported to increase upon treatment with AHR agonists in rodent tissues and cultured human cells. In this study, the mechanism of human metallothionein 2A (MT2A) gene transcription activation by AHR was investigated. Cotreatment with 3-methylcholanthrene and dexamethasone, agonists of AHR and GR respectively, synergistically increased MT2A mRNA levels in HepG2 cells. MT2A induction was suppressed by RNA interference against AHR or GR. Coimmunoprecipitation experiments revealed a physical interaction between AHR and GR proteins. Moreover, chromatin immunoprecipitation assays indicated that AHR was recruited to the glucocorticoid response element in the MT2A promoter. Thus, we provide a novel mechanism whereby AHR modulates expression of human MT2A via the glucocorticoid response element and protein–protein interactions with GR. - Highlights: • Aryl hydrocarbon receptor forms a complex with glucocorticoid receptor in cells. • Human metallothionein gene is regulated by the AHR and GR interaction. • AHR–GR complex binds to glucocorticoid response element in metallothionein gene. • We demonstrated a novel transcriptional mechanism via AHR and GR interaction

  7. Direct assessment of cumulative aryl hydrocarbon receptor agonist activity in sera from experimentally exposed mice and environmentally exposed humans

    DEFF Research Database (Denmark)

    Schlezinger, Jennifer J; Bernard, Pamela L; Haas, Amelia

    2010-01-01

    BACKGROUND: Aryl hydrocarbon receptor (AhR) ligands adversely affect many biological processes. However, assessment of the significance of human exposures is hampered by an incomplete understanding of how complex mixtures affect AhR activation/inactivation. OBJECTIVES: These studies used biologic...

  8. Induction of aryl hydrocarbon receptor-mediated and estrogen receptor-mediated activities, and modulation of cell proliferation by dinaphthofurans

    Czech Academy of Sciences Publication Activity Database

    Vondráček, Jan; Chramostová, Kateřina; Plíšková, M.; Bláha, L.; Brack, W.; Kozubík, Alois; Machala, M.

    2004-01-01

    Roč. 23, č. 9 (2004), s. 2214-2220 ISSN 0730-7268 R&D Projects: GA ČR GA525/03/1527 Institutional research plan: CEZ:AV0Z5004920 Keywords : aryl hydrocarbon receptor-mediated activity * estrogenicity * intercellular communication inhibition Subject RIV: BO - Biophysics Impact factor: 2.121, year: 2004

  9. Interactions between polymorphisms in the aryl hydrocarbon receptor signalling pathway and exposure to persistent organochlorine pollutants affect human semen quality

    DEFF Research Database (Denmark)

    Brokken, L J S; Lundberg, P J; Spanò, M

    2014-01-01

    Persistent organic pollutants (POPs) may affect male reproductive function. Many dioxin-like POPs exert their effects by activation of the aryl hydrocarbon receptor (AHR) signalling pathway. We analysed whether gene-environment interactions between polymorphisms in AHR (R554K) and AHR repressor (...

  10. Aryl hydrocarbon receptor-mediated and estrogenic activities of oxygenated polycyclic aromatic hydrocarbons and azaarenes originally identified in extracts of river sediments

    Czech Academy of Sciences Publication Activity Database

    Machala, M.; Ciganek, M.; Bláha, L.; Minksová, Kateřina; Vondráček, Jan

    2001-01-01

    Roč. 20, č. 12 (2001), s. 2736-2743 ISSN 0730-7268 R&D Projects: GA ČR GA525/98/1266 Institutional research plan: CEZ:AV0Z5004920 Keywords : aryl hydrocarbon-mediated activity * estrogenicity * reporter gene bioassays Subject RIV: BO - Biophysics Impact factor: 1.964, year: 2001

  11. The aryl hydrocarbon receptor meets immunology: friend or foe? A little of both

    Directory of Open Access Journals (Sweden)

    Walker eJulliard

    2014-10-01

    Full Text Available The aryl hydrocarbon receptor (AHR has long been studied by toxicologists as a ligand-activated transcription factor that is activated by dioxin and other environmental pollutants such as polycyclic aromatic hydrocarbons. The hallmark of AHR activation is the upregulation of the cytochrome P450 enzymes that metabolize many of these toxic compounds. However, recent findings demonstrate that both exogenous and endogenous AHR ligands can alter innate and adaptive immune responses including effects on T-cell differentiation. Kynurenine, a tryptophan breakdown product, is one such endogenous ligand of the AHR. Expression of indoleamine 2,3-dioxygenase by dendritic cells causes accumulation of kynurenine and results in subsequent tolerogenic effects including increased regulatory T cell activity. At the same time, polycyclic aromatic hydrocarbons found in pollution enhance Th17 differentiation in the lungs of exposed mice via the AHR. In this perspective, we will discuss the importance of the AHR in the immune system and the role this might play in normal physiology and response to disease.

  12. Activation of the Aryl Hydrocarbon Receptor Interferes with Early Embryonic Development

    Directory of Open Access Journals (Sweden)

    Manolis Gialitakis

    2017-11-01

    Full Text Available The transcriptional program of early embryonic development is tightly regulated by a set of well-defined transcription factors that suppress premature expression of differentiation genes and sustain the pluripotent identity. It is generally accepted that this program can be perturbed by environmental factors such as chemical pollutants; however, the precise molecular mechanisms remain unknown. The aryl hydrocarbon receptor (AHR is a widely expressed nuclear receptor that senses environmental stimuli and modulates target gene expression. Here, we have investigated the AHR interactome in embryonic stem cells by mass spectrometry and show that ectopic activation of AHR during early differentiation disrupts the differentiation program via the chromatin remodeling complex NuRD (nucleosome remodeling and deacetylation. The activated AHR/NuRD complex altered the expression of differentiation-specific genes that control the first two developmental decisions without affecting the pluripotency program. These findings identify a mechanism that allows environmental stimuli to disrupt embryonic development through AHR signaling.

  13. Potential protective mechanisms of aryl hydrocarbon receptor (AHR) signaling in benign prostatic hyperplasia

    Science.gov (United States)

    Mehta, Vatsal; Vezina, Chad M.

    2011-01-01

    The aryl hydrocarbon receptor (AHR) is an evolutionarily conserved ligand activated transcription factor best known for its role in mediating toxic responses to dioxin-like environmental contaminants. However, AHR signaling has also emerged as an active participant in processes of normal development and disease progression. Here, we review the role of AHR signaling in prostate development and disease processes, with a particular emphasis on benign prostatic hyperplasia (BPH). Inappropriate AHR activation has recently been associated with a decreased risk of symptomatic BPH in humans and has been shown to impair prostate development and disrupt endocrine signaling in rodents. We highlight known physiological responses to AHR activation in prostate and other tissues and discuss potential mechanisms by which it may act in adult human prostate to protect against symptomatic BPH. PMID:21684673

  14. Enzyme induction and histopathology elucidate aryl hydrocarbon receptor-mediated versus non-aryl hydrocarbon receptor-mediated effects of Aroclor 1268 in American mink (Neovison vison).

    Science.gov (United States)

    Folland, William R; Newsted, John L; Fitzgerald, Scott D; Fuchsman, Phyllis C; Bradley, Patrick W; Kern, John; Kannan, Kurunthachalam; Zwiernik, Matthew J

    2016-03-01

    Polychlorinated biphenyl (PCB) concentrations reported in preferred prey and blubber of bottlenose dolphins from the Turtle-Brunswick River estuary (Georgia, USA) suggest the potential for adverse effects. However, PCBs in Turtle-Brunswick River estuary dolphins are primarily derived from Aroclor 1268, and predicting toxic effects of Aroclor 1268 is uncertain because of the mixture's unique composition and associated physiochemical characteristics. These differences suggest that toxicity benchmarks for other PCB mixtures may not be relevant to dolphins exposed to Aroclor 1268. American mink (Neovison vison) were used as a surrogate model for cetaceans to characterize mechanisms of action associated with Aroclor 1268 exposure. Mink share similarities in phylogeny and life history with cetaceans and are characteristically sensitive to PCBs, making them an attractive surrogate species for marine mammals in ecotoxicity studies. Adult female mink and a subsequent F1 generation were exposed to Aroclor 1268 through diet, and effects on enzyme induction, histopathology, thyroid hormone regulation, hematology, organ weights, and body condition index were compared to a negative control and a 3,3',4,4',5-pentachlorobiphenyl (PCB 126)-positive control. Aroclor 1268 dietary exposure concentrations ranged from 1.8 µg/g wet weight to 29 µg/g wet weight. Anemia, hypothyroidism, and hepatomegaly were observed in mink exposed to Aroclor 1268 beyond various dietary thresholds. Cytochrome P450 induction and squamous epithelial proliferation jaw lesions were low in Aroclor 1268 treatments relative to the positive control. Differences in enzyme induction and the development of squamous epithelial proliferation jaw lesions between Aroclor 1268 treatments and the positive control, coupled with effects observed in Aroclor 1268 treatments not observed in the positive control, indicate that mechanisms additional to the aryl hydrocarbon receptor-mediated pathway are associated with

  15. Polymorphism of the aryl-hydrocarbon receptor gene in intron 10 of human cancers

    Directory of Open Access Journals (Sweden)

    M. Rocas

    2011-11-01

    Full Text Available Polychlorinated dibenzo-p-dioxins (PCDDs and related halogenated aromatic hydrocarbons (e.g., PCDFs, often called "dioxins", are ubiquitously present environmental contaminants. Some of them, notably 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, are among the most toxic synthetic compounds known. The biological effects of dioxins are mediated via the aryl hydrocarbon receptor (AhR. Mutations in the AhR transactivation domain are linked to sensitivity to the acute lethality of TCDD. We present here a study of AhR gene polymorphism in normal and cancer human tissues affecting pre-mRNA splicing in the AhR gene-coding transactivation domain region (exon 10, intron 10, exon 11 region, previously shown to be associated with AhR dysfunction. We tested 126 pairs of normal and cancer tissue samples from liver, lung, stomach, kidney, mucous, breast, and pancreas of 49 males and 77 females (45-70 years of age. We used in vitro splicing assay, RT-PCR and sequencing methods. Our results showed that in an in vitro system it is possible to reconstitute cellular pre-mRNA splicing events. Tested cancer tissues did not contain mutations in the AhR transactivation domain region when the DNA sequences were compared with those from normal tissues. There were also no differences in AhR mRNA splice variants between normal and malignant breast tissues and no polymorphisms in the studied regions or cDNA.

  16. Influence of some anti-inflammatory drugs on the activity of aryl hydrocarbon hydroxylase and the cytochrome P450 content

    Energy Technology Data Exchange (ETDEWEB)

    Mostafa, M.H.; Sheweita, S.A.; Abdel-Moneam, N.M. (Alexandria Univ. (Egypt))

    1990-06-01

    The metabolism of benzo({alpha})pyrene is mediated by the mixed function oxidase system including the cytochrome P450-dependent aryl hydrocarbon hydroxylase. The data of the present study revealed the ability of various commonly used anti-inflammatory drugs to alter the activity of this enzyme system, where all the tested drugs, namely phenyl butazone, ketoprofen, piroxicam, and acetaminophen, caused an increase in both the activity of aryl hydrocarbon hydroxylase and the cytochrome P450 content whether administered as a single dose or as a repeated dose for 6 consecutive days. The percentage of change for all drugs except phenyl butazone was proportional to the duration of drug administration. On the other hand, pyrazole which is chemically related to phenyl butazone, had no significant effect when administered as a single dose but caused a decrease in both studied parameters when administered as a repeated dose for 6 consecutive days. The mechanisms by which these commonly used drugs modify the aryl hydrocarbon hydroxylase activity and the cytochrome p450 content are discussed in the text.

  17. Exposure to atmospheric particulate matter enhances Th17 polarization through the aryl hydrocarbon receptor.

    Directory of Open Access Journals (Sweden)

    Michael van Voorhis

    Full Text Available Lung diseases, including asthma, COPD, and other autoimmune lung pathologies are aggravated by exposure to particulate matter (PM found in air pollution. IL-17 has been shown to exacerbate airway disease in animal models. As PM is known to contain aryl hydrocarbon receptor (AHR ligands and the AHR has recently been shown to play a role in differentiation of Th17 T cells, the aim of this study was to determine whether exposure to PM could impact Th17 polarization in an AHR-dependent manner. This study used both cell culture techniques and in vivo exposure in mice to examine the response of T cells to PM. Initially experiments were conducted with urban dust particles from a standard reference material, and ultimately repeated with freshly collected samples of diesel exhaust and cigarette smoke. The readout for the assays was increased T cell differentiation as indicated by increased generation of IL-17A in culture, and increased populations of IL-17 producing cells by intracellular flow cytometry. The data illustrate that Th17 polarization was significantly enhanced by addition of urban dust in a dose dependent fashion in cultures of wild-type but not AHR(-/- mice. The data further suggest that polycyclic aromatic hydrocarbons played a primary role in this enhancement. There was both an increase of Th17 cell differentiation, and also an increase in the amount of IL-17 secreted by the cells. In summary, this paper identifies a novel mechanism whereby PM can directly act on the AHR in T cells, leading to enhanced Th17 differentiation. Further understanding of the molecular mechanisms responsible for pathologic Th17 differentiation and autoimmunity seen after exposure to pollution will allow direct targeting of proteins involved in AHR activation and function for treatment of PM exposures.

  18. Detection of Aryl Hydrocarbon Receptor Activation by Some Chemicals in Food Using a Reporter Gene Assay.

    Science.gov (United States)

    Amakura, Yoshiaki; Tsutsumi, Tomoaki; Yoshimura, Morio; Nakamura, Masafumi; Handa, Hiroshi; Matsuda, Rieko; Teshima, Reiko; Watanabe, Takahiro

    2016-02-25

    The purpose of this study was to examine whether a simple bioassay used for the detection of dioxins (DXNs) could be applied to detect trace amounts of harmful DXN-like substances in food products. To identify substances with possible DXN-like activity, we assessed the ability of various compounds in the environment to bind the aryl hydrocarbon receptor (AhR) that binds specifically to DXNs. The compounds tested included 19 polycyclic aromatic hydrocarbons (PAHs), 20 PAH derivatives (nitrated, halogenated, and aminated derivatives), 23 pesticides, six amino acids, and eight amino acid metabolites. The AhR binding activities (AhR activity) of these compounds were measured using the chemical activated luciferase gene expression (CALUX) reporter gene assay system. The majority of the PAHs exhibited marked AhR activity that increased in a concentration-dependent manner. Furthermore, there was a positive link between AhR activity and the number of aromatic rings in the PAH derivatives. Conversely, there appeared to be a negative correlation between AhR activity and the number of chlorine residues present on halogenated PAH derivatives. However, there was no correlation between AhR activity and the number and position of substituents among nitrated and aminated derivatives. Among the pesticides tested, the indole-type compounds carbendazim and thiabendazole showed high levels of activity. Similarly, the indole compound tryptamine was the only amino acid metabolite to induce AhR activity. The results are useful in understanding the identification and characterization of AhR ligands in the CALUX assay.

  19. Association of Aryl Hydrocarbon Receptor-Related Gene Variants with the Severity of Autism Spectrum Disorders.

    Science.gov (United States)

    Fujisawa, Takashi X; Nishitani, Shota; Iwanaga, Ryoichiro; Matsuzaki, Junko; Kawasaki, Chisato; Tochigi, Mamoru; Sasaki, Tsukasa; Kato, Nobumasa; Shinohara, Kazuyuki

    2016-01-01

    Exposure to environmental chemicals, such as dioxin, is known to have adverse effects on the homeostasis of gonadal steroids, thereby potentially altering the sexual differentiation of the brain to express autistic traits. Dioxin-like chemicals act on the aryl hydrocarbon receptor (AhR), polymorphisms, and mutations of AhR -related gene may exert pathological influences on sexual differentiation of the brain, causing autistic traits. To ascertain the relationship between AhR -related gene polymorphisms and autism susceptibility, we identified genotypes of them in patients and controls and determined whether there are different gene and genotype distributions between both groups. In addition, to clarify the relationships between the polymorphisms and the severity of autism, we compared the two genotypes of AhR -related genes (rs2066853, rs2228099) with the severity of autistic symptoms. Although no statistically significant difference was found between autism spectrum disorder (ASD) patients and control individuals for the genotypic distribution of any of the polymorphisms studied herein, a significant difference in the total score of severity was observed in rs2228099 polymorphism, suggesting that the polymorphism modifies the severity of ASD symptoms but not ASD susceptibility. Moreover, we found that a significant difference in the social communication score of severity was observed. These results suggest that the rs2228099 polymorphism is possibly associated with the severity of social communication impairment among the diverse ASD symptoms.

  20. Pluripotency factors and Polycomb Group proteins repress aryl hydrocarbon receptor expression in murine embryonic stem cells

    Directory of Open Access Journals (Sweden)

    Chia-I Ko

    2014-01-01

    Full Text Available The aryl hydrocarbon receptor (AHR is a transcription factor and environmental sensor that regulates expression of genes involved in drug-metabolism and cell cycle regulation. Chromatin immunoprecipitation analyses, Ahr ablation in mice and studies with orthologous genes in invertebrates suggest that AHR may also play a significant role in embryonic development. To address this hypothesis, we studied the regulation of Ahr expression in mouse embryonic stem cells and their differentiated progeny. In ES cells, interactions between OCT3/4, NANOG, SOX2 and Polycomb Group proteins at the Ahr promoter repress AHR expression, which can also be repressed by ectopic expression of reprogramming factors in hepatoma cells. In ES cells, unproductive RNA polymerase II binds at the Ahr transcription start site and drives the synthesis of short abortive transcripts. Activation of Ahr expression during differentiation follows from reversal of repressive marks in Ahr promoter chromatin, release of pluripotency factors and PcG proteins, binding of Sp factors, establishment of histone marks of open chromatin, and engagement of active RNAPII to drive full-length RNA transcript elongation. Our results suggest that reversible Ahr repression in ES cells holds the gene poised for expression and allows for a quick switch to activation during embryonic development.

  1. Interaction of fish aryl hydrocarbon receptor paralogs (AHR1 and AHR2) with the retinoblastoma protein

    Energy Technology Data Exchange (ETDEWEB)

    Merson, Rebeka R., E-mail: rmerson@ric.edu [Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States); Biology Department, Rhode Island College, 500 Mt. Pleasant Ave., Providence, RI 02908 (United States); Karchner, Sibel I.; Hahn, Mark E. [Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States)

    2009-08-13

    The aryl hydrocarbon receptor (AHR) mediates the toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds. In some mammalian cell lines, TCDD induces G1 cell cycle arrest, which depends on an interaction between the AHR and the retinoblastoma tumor suppressor (RB). Mammals possess one AHR, whereas fishes possess two or more AHR paralogs that differ in the domains important for AHR-RB interactions in mammals. To test the hypothesis that fish AHR paralogs differ in their ability to interact with RB, we cloned RB cDNA from Atlantic killifish, Fundulus heteroclitus, and studied the interactions of killifish RB protein with killifish AHR1 and AHR2. In coimmunoprecipitation experiments, in vitro-expressed killifish RB coprecipitated with both AHR1 and AHR2. Consistent with these results, both killifish AHR1 and AHR2 interacted with RB in mammalian two-hybrid assays. These results suggest that both fish AHR1 and AHR2 paralogs may have the potential to influence cell proliferation through interactions with RB.

  2. Cell specific effects of PCB 126 on aryl hydrocarbone receptors in follicular cells of porcine ovaries

    Energy Technology Data Exchange (ETDEWEB)

    Wojtowicz, A.; Augustowska, K.; Gregoraszczuk, E. [Lab. of Physiology and Toxicology of Reproduction, Dept. of Animal Physiology, Inst. of Zoology, Jagiellonian Univ., Krakow (Poland)

    2004-09-15

    Polychlorinated biphenyles (PCBs) like other endocrine disrupters could interfere with natural hormones by binding to their receptors and thus mimicking the cellular response to them. They are known to possess either estrogenic or antiestrogenic properties. In our previous papers we demonstrated that PCBs are able to disrupt ovarian steroidogenesis. We found that the coplanar PCB 126 caused the decrease in estradiol secretion in whole cultured pig ovarian follicles. PCB 126 congener is structurally related to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Since TCDD effects are known to be mediated by aryl hydrocarbone receptors (AhRs), we decided to determine if PCB 126 affects signal transduction pathway activated by these receptors. It has been reported that the functional AhR is present in ovary including oocytes, granulosa and theca cells of rat, mouse, rhesus monkey and human ovary. Moreover, the expression of AhR in the rat ovary appeared to be estrous cycle-dependent, thus suggesting that AhR expression may be regulated by fluctuating hormone levels. This study was designed to investigate the effects of the non-ortho-substituted 3,3',4,4',5-pentachlorobiphenyl (PCB126) on the AhR activation, localization and protein level in pig ovarian follicle cells.

  3. Association of aryl hydrocarbon receptor-related gene variants with the severity of autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Takashi X. Fujisawa

    2016-11-01

    Full Text Available Exposure to environmental chemicals, such as dioxin, is known to have adverse effects on the homeostasis of gonadal steroids, thereby potentially altering the sexual differentiation of the brain to express autistic traits. Dioxin-like chemicals act on the aryl hydrocarbon receptor (AhR, polymorphisms and mutations of AhR-related gene may exert pathological influences on sexual differentiation of the brain, causing autistic traits. To ascertain the relationship between AhR-related gene polymorphisms and autism susceptibility, we identified genotypes of them in patients and controls and determined whether there are different gene and genotype distributions between both groups. In addition, to clarify the relationships between the polymorphisms and the severity of autism, we compared the two genotypes of AhR-related genes (rs2066853, rs2228099 with the severity of autistic symptoms. Although no statistically significant difference was found between autism spectrum disorder (ASD patients and control individuals for the genotypic distribution of any of the polymorphisms studied herein, a significant difference in the total score of severity was observed in rs2228099 polymorphism, suggesting that the polymorphism modifies the severity of ASD symptoms but not ASD susceptibility. Moreover, we found that a significant difference in the social communication score of severity was observed. These results suggest that the rs2228099 polymorphism is possibly associated with the severity of social communication impairment among the diverse ASD symptoms.

  4. Aryl hydrocarbon receptor regulates histone deacetylase 8 expression to repress tumor suppressive activity in hepatocellular carcinoma.

    Science.gov (United States)

    Wang, Li-Ting; Chiou, Shyh-Shin; Chai, Chee-Yin; Hsi, Edward; Wang, Shen-Nien; Huang, Shau-Ku; Hsu, Shih-Hsien

    2017-01-31

    Histone deacetylase 8 (HDAC8), a unique member of class I histone deacetylases, shows remarkable correlation with advanced disease stage and multiple malignant tumors However, little is known about the contribution of HDAC8 to the tumorigenesis of hepatocellular carcinoma (HCC). The present study investigated the expression of HDAC8 regulated by the aryl hydrocarbon receptor (AHR) in HCC cell lines and tissues, and the roles of HDAC8 overexpression in cell proliferation, including potentially underlying mechanisms. We assessed the correlation between the clinic-pathological parameters and the expression of AHR and HDAC8. Further, we analyzed the AHR siRNA transfection and HDAC8 inhibitors to explore the functions of HDAC8 in HCC progression in vitro and in vivo. In a panel of 289 HCC patients, HDAC8 was shown to be highly correlated with AHR expression at both mRNA and protein levels. HCC patients with high AHR expression showed a shorter survival time than that with low AHR expression. We then found that the expression of both AHR and HDAC8 was significantly upregulated in both HCC cell lines and tumor tissues compared to human normal hepatocytes and matched non-tumor tissues. Furthermore, HDAC8 inhibition remarkably inhibited hepatoma cell proliferation and transformation activity via upregulation of RB1 in vitro and in vivo. Our data revealed an important role of the AHR-HDAC8 axis in promoting HCC tumorigenesis, thus identifying HDAC8 as a potential therapeutic target for HCC treatment.

  5. Growth suppression of Leydig TM3 cells mediated by aryl hydrocarbon receptor

    International Nuclear Information System (INIS)

    Iseki, Minoru; Ikuta, Togo; Kobayashi, Tetsuya; Kawajiri, Kaname

    2005-01-01

    Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin induces developmental toxicity in reproductive organs. To elucidate the function of AhR, we generated stable transformants of TM3 cells overexpressing wild-type aryl hydrocarbon receptor (AhR) or its mutants which carried mutations in nuclear localization signal or nuclear export signal. In the presence of 3-methylcholanthrene (MC), proliferation of the cells transfected with wild-type AhR was completely suppressed, whereas cells expressing AhR mutants proliferated in a manner equivalent to control TM3 cells, suggesting AhR-dependent growth inhibition. The suppression was associated with up-regulation of cyclin-dependent kinase inhibitor p21 Cip1 , which was abolished by pretreatment with actinomycin D. A p38 MAPK specific inhibitor, SB203580, blocked the increase of p21 Cip1 mRNA in response to MC. Treatment with indigo, another AhR ligand, failed to increase of p21 Cip1 mRNA, although up-regulation of mRNA for CYP1A1 was observed. These data suggest AhR in Leydig cells mediates growth inhibition by inducing p21 Cip1

  6. Hepatic Aryl hydrocarbon Receptor Nuclear Translocator (ARNT regulates metabolism in mice.

    Directory of Open Access Journals (Sweden)

    Christopher H Scott

    Full Text Available Aryl hydrocarbon Receptor Nuclear Translocator (ARNT and its partners hypoxia-inducible factors (HIF-1α and HIF-2α are candidate factors for the well-known link between the liver, metabolic dysfunction and elevation in circulating lipids and glucose. Methods: Hepatocyte-specific ARNT-null (LARNT, HIF-1α-null (LHIF1α and HIF-2α-null (LHIF2α mice were created.LARNT mice had increased fasting glucose, impaired glucose tolerance, increased glucose production, raised post-prandial serum triglycerides (TG and markedly lower hepatic ATP versus littermate controls. There was increased expression of G6Pase, Chrebp, Fas and Scd-1 mRNAs in LARNT animals. Surprisingly, LHIF1α and LHIF2α mice exhibited no alterations in any metabolic parameter assessed.These results provide convincing evidence that reduced hepatic ARNT can contribute to inappropriate hepatic glucose production and post-prandial dyslipidaemia. Hepatic ARNT may be a novel therapeutic target for improving post-prandial hypertriglyceridemia and glucose homeostasis.

  7. Cobaltous chloride and hypoxia inhibit aryl hydrocarbon receptor-mediated responses in breast cancer cells

    International Nuclear Information System (INIS)

    Khan, Shaheen; Liu Shengxi; Stoner, Matthew; Safe, Stephen

    2007-01-01

    The aryl hydrocarbon receptor (AhR) is expressed in estrogen receptor (ER)-positive ZR-75 breast cancer cells. Treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces CYP1A1 protein and mRNA levels and also activates inhibitory AhR-ERα crosstalk associated with hormone-induced reporter gene expression. In ZR-75 cells grown under hypoxia, induction of these AhR-mediated responses by TCDD was significantly inhibited. This was not accompanied by decreased nuclear AhR levels or decreased interaction of the AhR complex with the CYP1A1 gene promoter as determined in a chromatin immunoprecipitation assay. Hypoxia-induced loss of Ah-responsiveness was not associated with induction of hypoxia-inducible factor-1α or other factors that sequester the AhR nuclear translocation (Arnt) protein, and overexpression of Arnt under hypoxia did not restore Ah-responsiveness. The p65 subunit of NFκB which inhibits AhR-mediated transactivation was not induced by hypoxia and was primarily cytosolic in ZR-75 cells grown under hypoxic and normoxic conditions. In ZR-75 cells maintained under hypoxic conditions for 24 h, BRCA1 (an enhancer of AhR-mediated transactivation in breast cancer cells) was significantly decreased and this contributed to loss of Ah-responsiveness. In cells grown under hypoxia for 6 h, BRCA1 was not decreased, but induction of CYP1A1 by TCDD was significantly decreased. Cotreatment of ZR-75 cells with TCDD plus the protein synthesis inhibitor cycloheximide for 6 h enhanced CYP1A1 expression in cells grown under hypoxia and normoxia. These results suggest that hypoxia rapidly induces protein(s) that inhibit Ah-responsiveness and these may be similar to constitutively expressed inhibitors of Ah-responsiveness (under normoxia) that are also inhibited by cycloheximide

  8. Serum aryl hydrocarbon receptor ligand activity is associated with insulin resistance and resulting type 2 diabetes.

    Science.gov (United States)

    Roh, Eun; Kwak, Soo Heon; Jung, Hye Seung; Cho, Young Min; Pak, Youngmi Kim; Park, Kyong Soo; Kim, Seong Yeon; Lee, Hong Kyu

    2015-06-01

    Dioxin or dioxin-like compounds are ligands of the aryl hydrocarbon receptor (AhR), which is a ligand-activated nuclear transcription factor. There are limited studies about the association of serum AhR ligand activities and T2DM. Our objective was to investigate the association of serum AhR ligand activities with T2DM and its related metabolic parameters. This case-control study involved 83 subjects with T2DM as well as age-, sex-, and body mass index (BMI)-matched subjects with impaired glucose tolerance (IGT, n = 130) and normal glucose tolerance (NGT, n = 83). Serum AhR ligand activities were measured using a cell-based AhR ligand assay and standardized as 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TCDDeq, pmol/l). The T2DM group had the highest AhR ligand activities compared to the IGT and NGT groups [median (interquartile range), 68.1 (53.1, 81.5), 60.2 (45.8, 75.1), and 53.3 (46.1, 63.7) pmol/l, respectively; P = 0.003]. In the multivariate analysis, the log2-transformed TCDDeq levels were significantly associated with the risk of T2DM after adjusting for age, sex, and BMI (odds ratio 2.26, 95 % confidence interval 1.34-3.82; P = 0.002). In nondiabetic subjects, serum AhR ligand activities showed a positive correlation with fasting glucose and insulin concentrations and the homeostasis model assessment of insulin resistance, but showed a negative correlation with adiponectin concentrations. Serum AhR ligand activities were higher in the T2DM group and were correlated with the parameters of insulin resistance. Further investigation is required to elucidate the causal relationship between AhR ligand activity and T2DM.

  9. Lactobacillus bulgaricus OLL1181 activates the aryl hydrocarbon receptor pathway and inhibits colitis

    Science.gov (United States)

    Takamura, Takeyuki; Harama, Daisuke; Fukumoto, Suguru; Nakamura, Yuki; Shimokawa, Naomi; Ishimaru, Kayoko; Ikegami, Shuji; Makino, Seiya; Kitamura, Masanori; Nakao, Atsuhito

    2011-01-01

    Increasing evidence suggests that the aryl hydrocarbon receptor (AhR) pathway has an important role in the regulation of inflammatory responses. Most recently, we have shown that the activation of the AhR pathway by a potent AhR agonist inhibits the development of dextran sodium sulfate (DSS)-induced colitis, a model of human ulcerative colitis, by the induction of prostaglandin E2 (PGE2) in the large intestine. Because several strains of probiotic lactic acid bacteria have been reported to inhibit DSS-induced colitis by unidentified mechanisms, we hypothesized that particular strains of lactic acid bacterium might have the potential to activate the AhR pathway, thereby inhibiting DSS-induced colitis. This study investigated whether there are specific lactic acid bacterial strains that can activate the AhR pathway, and if so, whether this AhR-activating potential is associated with suppression of DSS-induced colitis. By using AhR signaling reporter cells, we found that Lactobacillus bulgaricus OLL1181 had the potential to activate the AhR pathway. OLL1181 also induced the mRNA expression of cytochrome P450 family 1A1 (CYP1A1), a target gene of the AhR pathway, in human colon cells, which was inhibited by the addition of an AhR antagonist, α-naphthoflavon (αNF). In addition, mice treated orally with OLL1181 showed an increase in CYP1A1 mRNA expression in the large intestine and amelioration of DSS-induced colitis. Thus, OLL1181 can induce activation of the intestinal AhR pathway and inhibit DSS-induced colitis in mice. This strain of lactic acid bacterium has therefore the potential to activate the AhR pathway, which may be able to suppress colitis. PMID:21321579

  10. Tissue distribution of aryl hydrocarbon receptor in the intestine: Implication of putative roles in tumor suppression

    International Nuclear Information System (INIS)

    Ikuta, Togo; Kurosumi, Masafumi; Yatsuoka, Toshimasa; Nishimura, Yoji

    2016-01-01

    Intestinal homeostasis is maintained by complex interactions between intestinal microorganisms and the gut immune system. Dysregulation of gut immunity may lead to inflammatory disorders and tumorigenesis. We previously have shown the tumor suppressive effects of aryl hydrocarbon receptor (AhR) in intestinal carcinogenesis. In the present study, we investigated AhR distribution in the mouse and human intestine by histochemical analysis. In the normal intestine, AhR was mainly localized in the stroma containing immune cells in the lamina propria and lymphoid follicles. On the other hand, in the tumor tissue from human colon cancer and that developed in Apc Min/+ mice, AhR expression was elevated. AhR immunostaining was found in both stromal and tumor cells. Although AhR was localized in the cytoplasm of tumor cells in most cases, nuclear AhR was also observed in some. AhR knockdown using siRNA resulted in significant promotion of cell growth in colon cancer cell lines. Furthermore, AhR activation by AhR ligands supplemented in culture medium suppressed cell growth. Our study results suggest that tumor suppressive roles of AhR are estimated in two distinct ways: in normal tissue, AhR is associated with tumor prevention by regulating gut immunity, whereas in tumor cells, it is involved in growth suppression. - Highlights: • In the normal intestine, AhR was mainly localized in stroma containing immune cells. • In the tumor tissue, AhR expression was found in both stromal and tumor cells. • AhR knockdown promoted cell growth in colon cancer cell lines.

  11. Aryl Hydrocarbon Receptor Activation Suppresses EBF1 and PAX5 and Impairs Human B Lymphopoiesis.

    Science.gov (United States)

    Li, Jinpeng; Bhattacharya, Sudin; Zhou, Jiajun; Phadnis-Moghe, Ashwini S; Crawford, Robert B; Kaminski, Norbert E

    2017-11-15

    Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates biological responses to endogenous and environmental chemical cues. Increasing evidence shows that the AHR plays physiological roles in regulating development, homeostasis, and function of a variety of cell lineages in the immune system. However, the role of AHR in human B cell development has not been investigated. Toward this end, an in vitro feeder-free human B cell developmental model system was employed using human cord blood CD34 + hematopoietic stem/progenitor cells. Using this model, we found that AHR activation by the high-affinity ligand 2,3,7,8-tetrachlorodibenzo- p -dioxin significantly suppressed the generation of early B cells and pro-B cells from hematopoietic stem/progenitor cells, indicating the impairment of B cell lineage specification and commitment. Addition of an AHR antagonist reversed 2,3,7,8-tetrachlorodibenzo- p -dioxin-elicited suppression of early B and pro-B cells, suggesting a role of AHR in regulating B lymphopoiesis. Gene expression analysis revealed a significant decrease in the messenger RNA level of early B cell factor 1 (EBF1) and paired box 5, two critical transcription factors directing B cell lineage specification and commitment. Additionally, binding of the ligand-activated AHR to the putative dioxin response elements in the EBF1 promoter was demonstrated by EMSAs and chromatin immunoprecipitation analysis, suggesting transcriptional regulation of EBF1 by AHR. Taken together, this study demonstrates a role for the AHR in regulating human B cell development, and it suggests that transcriptional alterations of EBF1 by the AHR are involved in the underlying mechanism. Copyright © 2017 by The American Association of Immunologists, Inc.

  12. Prostate tumor progression in the TRAMP mouse. Protective effects of the aryl hydrocarbon receptor

    Energy Technology Data Exchange (ETDEWEB)

    Fritz, W.; Lin, T.M.; Peterson, R. [Wisconsin Univ., Madison, WI (United States)

    2004-09-15

    The developing male reproductive system is highly sensitive to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD binds to the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, to produce sustained alterations in gene expression. Mice lacking the AhR (AhRKO, Ahr{sup -/-}) have permitted further characterization of the role of the AhR in mediating TCDD effects and revealed a physiological role for the AhR in normal development. We previously demonstrated that in utero and lactational TCDD exposure significantly reduced ventral, dorsolateral and anterior prostate weights, and that these effects were dependent on the AhR5. However, reductions in prostate lobe weights in untreated, AhRKO mice compared to wild-type counterparts at various ages demonstrated that the AhR signaling pathway is involved in normal development of the dorsolateral and anterior prostates, but apparently not the ventral prostate. Unaltered serum testosterone concentrations and modest reduction in serum 5{alpha}-androstane-3{alpha},17{beta}a-diol concentrations could not account for reductions in prostate weights in mice lacking AhR (Ahr{sup -/-}). Normal histology and lack of alteration in androgen receptor mRNA levels further indicate that the reduction in prostate weights is not a result of reduced androgen action in AhRKO mice. The observation that regulation of early prostate growth in mice occurs following AhR activation by TCDD, as well as by loss of AhR, suggests that the AhR may also regulate aberrant prostate growth that results from ''reawakening'' of the prostate growth regulatory signals later in life. Our objective was to determine if the AhR signaling pathway has an effect on prostate cancer development.

  13. Tissue distribution of aryl hydrocarbon receptor in the intestine: Implication of putative roles in tumor suppression

    Energy Technology Data Exchange (ETDEWEB)

    Ikuta, Togo, E-mail: togo@cancer-c.pref.saitama.jp [Department of Cancer Prevention, Research Institute for Clinical Oncology, Saitama Cancer Center, 818 Komuro, Ina-machi, Kitaadachi-gun, Saitama 362-0806 (Japan); Kurosumi, Masafumi, E-mail: mkurosumi@cancer-c.pref.saitama.jp [Division of Pathology, Saitama Cancer Center, 780 Komuro, Ina-machi, Kitaadachi-gun, Saitama 362-0806 (Japan); Yatsuoka, Toshimasa, E-mail: yatsuoka-gi@umin.ac.jp [Division of Gastroenterological Surgery, Saitama Cancer Center, 780 Komuro, Ina-machi, Kitaadachi-gun, Saitama 362-0806 (Japan); Nishimura, Yoji, E-mail: yojinish@cancr-c.pref.saitama.jp [Division of Gastroenterological Surgery, Saitama Cancer Center, 780 Komuro, Ina-machi, Kitaadachi-gun, Saitama 362-0806 (Japan)

    2016-05-01

    Intestinal homeostasis is maintained by complex interactions between intestinal microorganisms and the gut immune system. Dysregulation of gut immunity may lead to inflammatory disorders and tumorigenesis. We previously have shown the tumor suppressive effects of aryl hydrocarbon receptor (AhR) in intestinal carcinogenesis. In the present study, we investigated AhR distribution in the mouse and human intestine by histochemical analysis. In the normal intestine, AhR was mainly localized in the stroma containing immune cells in the lamina propria and lymphoid follicles. On the other hand, in the tumor tissue from human colon cancer and that developed in Apc{sup Min/+}mice, AhR expression was elevated. AhR immunostaining was found in both stromal and tumor cells. Although AhR was localized in the cytoplasm of tumor cells in most cases, nuclear AhR was also observed in some. AhR knockdown using siRNA resulted in significant promotion of cell growth in colon cancer cell lines. Furthermore, AhR activation by AhR ligands supplemented in culture medium suppressed cell growth. Our study results suggest that tumor suppressive roles of AhR are estimated in two distinct ways: in normal tissue, AhR is associated with tumor prevention by regulating gut immunity, whereas in tumor cells, it is involved in growth suppression. - Highlights: • In the normal intestine, AhR was mainly localized in stroma containing immune cells. • In the tumor tissue, AhR expression was found in both stromal and tumor cells. • AhR knockdown promoted cell growth in colon cancer cell lines.

  14. Dietary tryptophan alleviates dextran sodium sulfate-induced colitis through aryl hydrocarbon receptor in mice.

    Science.gov (United States)

    Islam, Jahidul; Sato, Shoko; Watanabe, Kouichi; Watanabe, Takaya; Ardiansyah; Hirahara, Keisuke; Aoyama, Yukihide; Tomita, Shuhei; Aso, Hisashi; Komai, Michio; Shirakawa, Hitoshi

    2017-04-01

    Ulcerative colitis is the typical progression of chronic inflammatory bowel disease. Amino acids, particularly tryptophan, have been reported to exert a protective effect against colitis induced by dextran sodium sulfate (DSS), but the precise underlying mechanisms remain incompletely clarified. Tryptophan metabolites are recognized to function as endogenous ligands for aryl hydrocarbon receptor (Ahr), which is a critical regulator of inflammation and immunity. Thus, we conducted this study to investigate whether dietary tryptophan supplementation protects against DSS-induced colitis by acting through Ahr. Female wild-type (WT) and Ahr-deficient (knockout; KO) mice (10-12 weeks old) were divided into four groups and fed either a control or 0.5% tryptophan diet. The tryptophan diet ameliorated DSS-induced colitis symptoms and severity in WT mice but not in KO mice, and the diet reduced the mRNA expression of Il-6, Tnfα, Il-1β and the chemokines Ccl2, Cxcl1 and Cxcl2 in the WT groups. Furthermore, Il-22 and Stat3 mRNA expression in the colon was elevated in WT mice fed with the tryptophan diet, which mainly protected epithelial layer integrity, and Ahr also modulated immune homeostasis by regulating Foxp3 and Il-17 mRNA expression. These data suggest that tryptophan-containing diet might ameliorate DSS-induced acute colitis and regulate epithelial homeostasis through Ahr. Thus, tryptophan could serve as a promising preventive agent in the treatment of ulcerative colitis. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Aryl hydrocarbon receptor downregulates MYCN expression and promotes cell differentiation of neuroblastoma.

    Directory of Open Access Journals (Sweden)

    Pei-Yi Wu

    Full Text Available Neuroblastoma (NB is the most common malignant disease of infancy. MYCN amplification is a prognostic factor for NB and is a sign of highly malignant disease and poor patient prognosis. In this study, we aimed to investigate novel MYCN-related genes and assess how they affect NB cell behavior. The different gene expression found in 10 MYCN amplification NB tumors and 10 tumors with normal MYCN copy number were analyzed using tissue oligonucleotide microarrays. Ingenuity Pathway Analysis was subsequently performed to identify the potential genes involved in MYCN regulation pathways. Aryl hydrocarbon receptor (AHR, a receptor for dioxin-like compounds, was found to be inversely correlated with MYCN expression in NB tissues. This correlation was confirmed in a further 14 human NB samples. Moreover, AHR expression in NB tumors was found to correlate highly with histological grade of differentiation. In vitro studies revealed that AHR overexpression in NB cells induced spontaneous cell differentiation. In addition, it was found that ectopic expression of AHR suppressed MYCN promoter activity resulting in downregulation of MYCN expression. The suppression effect of AHR on the transcription of MYCN was compensated for by E2F1 overexpression, indicating that E2F1 is involved in the AHR-regulating MYCN pathway. Furthermore, AHR shRNA promotes the expression of E2F1 and MYCN in NB cells. These findings suggest that AHR is one of the upstream regulators of MYCN. Through the modulation of E2F1, AHR regulates MYCN gene expression, which may in turn affect NB differentiation.

  16. The aryl hydrocarbon receptor: differential contribution to T helper 17 and T cytotoxic 17 cell development.

    Directory of Open Access Journals (Sweden)

    Mark D Hayes

    Full Text Available The aryl hydrocarbon receptor (AhR has been shown to be required for optimal Thelper (Th 17 cell activation. Th17 cells provide immunity against extracellular pathogens and are implicated in autoimmune diseases. Herein, the role of the AhR in cytokine production by Th17, and by the analogous population of T cytotoxic (Tc17 cells, has been examined. Lymph node Tc (CD8(+ and Th (CD4(+ cells were isolated by negative selection from naive AhR(+/- and AhR(-/- mice and polarised to Tc1/Th1 or Tc17/Th17 phenotypes with appropriate cytokines. Cell differentiation was assessed as a function of mRNA and protein (ELISA and flow cytometry expression for interferon (IFN-γ and for key Th17 cytokines. In AhR(+/- mice, Th17 cells displayed an exclusive IL-17 profile, which was markedly inhibited by a selective AhR antagonist to levels observed in AhR knockout mice. Addition of the natural AhR agonist 6-formylindolo[3,2-b]carbazole (FICZ markedly enhanced Th17 cell activity in the heterozygotes. In contrast, Tc17 cells polarised into 3 distinct subsets: producing either IL-17 or IFN-γ alone, or both cytokines. Blocking AhR was also detrimental to Tc17 development, with reduced responses recorded in AhR(-/- mice and antagonist-mediated reduction of IL-17 expression in the heterozygotes. However, Tc17 cells were largely refractory to exogenous FICZ, presumably because Tc17 cells express baseline AhR mRNA, but unlike Th17 cells, there is no marked up-regulation during polarisation. Thus, Th17 cell development is more dependent upon AhR activation than is Tc17 cell development, suggesting that endogenous AhR ligands play a much greater role in driving Th17 cell responses.

  17. The aryl hydrocarbon receptor is required for normal gonadotropin responsiveness in the mouse ovary

    International Nuclear Information System (INIS)

    Barnett, Kimberly R.; Tomic, Dragana; Gupta, Rupesh K.; Babus, Janice K.; Roby, Katherine F.; Terranova, Paul F.; Flaws, Jodi A.

    2007-01-01

    The aryl hydrocarbon receptor (AHR) mediates the toxicity of a variety of environmental chemicals. Although little is known about the physiological role of the AHR, studies suggest that it plays an important role in regulating ovulation because Ahr deficient (AhRKO) mice have a reduced number of ovulations compared to wild-type (WT) mice. The reasons for the reduced ability of AhRKO mice to ovulate are unknown. Normal ovulation, however, requires estrous cyclicity, appropriate luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, and LH and FSH responsiveness. Thus, the purpose of this study was to test the hypothesis that Ahr deletion regulates ovulation by altering cyclicity, FSH and LH levels, follicle-stimulating hormone receptor (Fshr) and luteinizing hormone receptor (Lhcgr) levels and/or gonadotropin responsiveness. The data indicate that AhRKO and WT mice have similar levels of FSH and LH, but AhRKO mice have reduced Fshr and Lhcgr mRNA levels compared to WT mice. Furthermore, AhRKO ovaries contain fewer corpora lutea compared to WT ovaries after 5 IU equine chorionic gonadotropin (eCG) treatment. Lastly, both AhRKO and WT mice ovulate a similar number of eggs in response to 5 IU human chorionic gonadotropin (hCG), but AhRKO mice ovulate fewer eggs than WT mice in response to 2.5 IU and 1.25 IU hCG. Collectively, these data indicate that AhRKO follicles have a reduced capacity to ovulate compared to WT follicles and that this is due to reduced responsiveness to gonadotropins. Thus, in addition to mediating toxicity of environmental chemicals, the Ahr is required for normal ovulation

  18. γ-Tocotrienol upregulates aryl hydrocarbon receptor expression and enhances the anticancer effect of baicalein

    Energy Technology Data Exchange (ETDEWEB)

    Yamashita, Shuya; Baba, Kiwako; Makio, Akiko; Kumazoe, Motofumi; Huang, Yuhui; Lin, I-Chian; Bae, Jaehoon; Murata, Motoki; Yamada, Shuhei; Tachibana, Hirofumi, E-mail: tatibana@agr.kyushu-u.ac.jp

    2016-05-13

    Previous studies have identified biomolecules that mediate the physiological actions of food factors, such as amino acids, vitamins, fatty acids, minerals, plant polyphenols, and lactobacilli, suggesting that our bodies are equipped with an innate system that senses which food factors are required to maintain our health. However, the effects of environmental factors on food factor sensing (FFS) remains largely unknown. Tocotorienols (T3s), which belongs to the vitamin E family, possess several physiological functions, including cholesterol lowering and neuroprotective effects. Here, we investigated the effects of naturally abundant γ-T3 on FFS-related gene expressions in melanoma using a DNA chip. Our results showed that γ-T3 increased the expression level of aryl hydrocarbon receptor (AhR), a sensing molecule to plant polyphenol baicalein. The co-treatment with γ-T3 and baicalein enhanced the anti-proliferative activity of baicalein, accompanied by the downstream events of AhR-activation induced by baicalein. These data suggest that γ-T3 upregulates AhR expression and enhances its sensitivity to baicalein. - Highlights: • γ-T3 upregulated the expression of AhR in mouse melanoma. • Promotion of the binding activity of Sp1 is associated with the increasing effect of γ-T3 on AhR expression. • γ-T3 enhanced the anti-proliferative activity of baicalein that has an AhR ligand activity. • γ-T3 enhanced the inducing activity of baicalein on the expression of AhR target genes.

  19. Insulin like growth factor 2 regulation of aryl hydrocarbon receptor in MCF-7 breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Tomblin, Justin K.; Salisbury, Travis B., E-mail: salisburyt@marshall.edu

    2014-01-17

    Highlights: •IGF-2 stimulates concurrent increases in AHR and CCND1 expression. •IGF-2 promotes the binding of AHR to the endogenous cyclin D1 promoter. •AHR knockdown inhibits IGF-2 stimulated increases in CCND1 mRNA and protein. •AHR knockdown inhibits IGF-2 stimulated increases in MCF-7 proliferation. -- Abstract: Insulin like growth factor (IGF)-1 and IGF-2 stimulate normal growth, development and breast cancer cell proliferation. Cyclin D1 (CCND1) promotes cell cycle by inhibiting retinoblastoma protein (RB1). The aryl hydrocarbon receptor (AHR) is a major xenobiotic receptor that also regulates cell cycle. The purpose of this study was to investigate whether IGF-2 promotes MCF-7 breast cancer proliferation by inducing AHR. Western blot and quantitative real time PCR (Q-PCR) analysis revealed that IGF-2 induced an approximately 2-fold increase (P < .001) in the expression of AHR and CCND1. Chromatin immunoprecipitation (ChIP), followed by Q-PCR indicated that IGF-2 promoted (P < .001) a 7-fold increase in AHR binding on the CCND1 promoter. AHR knockdown significantly (P < .001) inhibited IGF-2 stimulated increases in CCND1 mRNA and protein. AHR knockdown cells were less (P < .001) responsive to the proliferative effects of IGF-2 than control cells. Collectively, our findings have revealed a new regulatory mechanism by which IGF-2 induction of AHR promotes the expression of CCND1 and the proliferation of MCF-7 cells. This previously uncharacterized pathway could be important for the proliferation of IGF responsive cancer cells that also express AHR.

  20. Aryl Hydrocarbon Receptor Activation Reduces Dendritic Cell Function during Influenza Virus Infection

    Science.gov (United States)

    Jin, Guang-Bi; Moore, Amanda J.; Head, Jennifer L.; Neumiller, Joshua J.; Lawrence, B. Paige

    2010-01-01

    It has long been known that activation of the aryl hydrocarbon receptor (AhR) by ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) suppresses T cell–dependent immune responses; however, the underlying cellular targets and mechanism remain unclear. We have previously shown that AhR activation by TCDD reduces the proliferation and differentiation of influenza virus–specific CD8+ T cells through an indirect mechanism; suggesting that accessory cells are critical AhR targets during infection. Respiratory dendritic cells (DCs) capture antigen, migrate to lymph nodes, and play a key role in activating naive CD8+ T cells during respiratory virus infection. Herein, we report an examination of how AhR activation alters DCs in the lung and affects their trafficking to and function in the mediastinal lymph nodes (MLN) during infection with influenza virus. We show that AhR activation impairs lung DC migration and reduces the ability of DCs isolated from the MLN to activate naive CD8+ T cells. Using novel AhR mutant mice, in which the AhR protein lacks its DNA-binding domain, we show that the suppressive effects of TCDD require that the activated AhR complex binds to DNA. These new findings suggest that AhR activation by chemicals from our environment impacts DC function to stimulate naive CD8+ T cells and that immunoregulatory genes within DCs are critical targets of AhR. Moreover, our results reinforce the idea that environmental signals and AhR ligands may contribute to differential susceptibilities and responses to respiratory infection. PMID:20498003

  1. 1,8-cineole prevents UVB-induced skin carcinogenesis by targeting the aryl hydrocarbon receptor

    Science.gov (United States)

    Park, Joon; Kim, Yong Ho; Lee, Nam Hyouck; Kim, Young Eon; Kim, Yoonsook; Song, Kyung-Mo; Jung, Sung Keun

    2017-01-01

    1,8-cineole is a natural monoterpene cyclic ether present in Eucalyptus, and has been reported to exhibit anti-inflammatory and antioxidant effects. However, the preventive effect of 1,8-cineole on skin carcinogenesis and the molecular mechanism of action responsible remains unknown. In the present study, we investigated the effect of 1,8-cineole on UVB-induced skin carcinogenesis. 1,8-cineole inhibited UVB-induced cyclooxygenase-2 (COX-2) protein and mRNA expression and prostaglandin E2 (PGE2) generation in HaCaT cells. 1,8-cineole also inhibited phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, and phosphorylation of its upstream kinases, c-Src and epidermal growth factor receptor (EGFR). Quantitative real-time RT-PCR (qRT-PCR) and drug affinity responsive target stability (DARTS) assay results showed that 1,8-cineole suppressed UVB-induced expression of a target gene of the aryl hydrocarbon receptor (AhR), cyp1a1, and directly binds to AhR. Knockdown of AhR suppressed COX-2 expression as well as phosphorylation of ERK1/2 in HaCaT cells. Furthermore, topical treatment of 1,8-cineole on mouse skin delayed tumor incidence and reduced tumor numbers, while inhibiting COX-2 expression in vivo. Taken together, these results suggest that 1,8-cineole is a potent chemopreventive agent that inhibits UVB-induced COX-2 expression by targeting AhR to suppress UVB-induced skin carcinogenesis. PMID:29285309

  2. Secondhand Tobacco Smoke Exposure Associations With DNA Methylation of the Aryl Hydrocarbon Receptor Repressor.

    Science.gov (United States)

    Reynolds, Lindsay M; Magid, Hoda S; Chi, Gloria C; Lohman, Kurt; Barr, R Graham; Kaufman, Joel D; Hoeschele, Ina; Blaha, Michael J; Navas-Acien, Ana; Liu, Yongmei

    2017-04-01

    Cigarette smoking is inversely associated with DNA methylation of the aryl hydrocarbon receptor repressor (AHRR; cg05575921). However, the association between secondhand tobacco smoke (SHS) exposure and AHRR methylation is unknown. DNA methylation of AHRR cg05575921 in CD14+ monocyte samples, from 495 never-smokers and 411 former smokers (having quit smoking ≥15 years) from the Multi-Ethnic Study of Atherosclerosis (MESA), was cross-sectionally compared with concomitantly ascertained self-reported SHS exposure, urine cotinine concentrations, and estimates of air pollutants at participants' homes. Linear regression was used to test for associations, and covariates included age, sex, race, education, study site, and previous smoking exposure (smoking status, time since quitting, and pack-years). Recent indoor SHS exposure (hours per week) was inversely associated with cg05575921 methylation (β ± SE = -0.009 ± 0.003, p = .007). The inverse effect direction was consistent (but did not reach significance) in the majority of stratified analyses (by smoking status, sex, and race). Categorical analysis revealed high levels of recent SHS exposure (≥10 hours per week) inversely associated with cg05575921 methylation (β ± SE = -0.28 ± 0.09, p = .003), which remained significant (p effect of SHS on human DNA methylation. In the present study, we evaluated the association between SHS exposure and DNA methylation in human monocytes, at a site (AHRR cg05575921) known to have methylation inversely associated with current and former cigarette smoking compared to never smoking. Results from this study suggest high levels of recent SHS exposure inversely associate with DNA methylation of AHRR cg05575921 in monocytes from nonsmokers, albeit with weaker effects than active cigarette smoking. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Cancer immunoediting and dioxin-activating aryl hydrocarbon receptor: a missing link in the shift toward tumor immunoescape?

    OpenAIRE

    Ruggero Ridolfi; Massimo Guidoboni; Laura Ridolfi

    2010-01-01

    The aryl hydrocarbon receptor (AhR), a member of the PAS protein family, is found in organisms as diverse as Drosophila melano­gaster, nematodes, and mammals. While several reviews have reported that AhR, once activated by agonist ligands, causes long-term effects such as modification of cell growth through cell cycle control, there is also recent evidence of its decisive role in immunosuppression. The most widely studied AhR agonist is 2,3,7,8-tetrachlorodibenzo-p-dioxin, which binds AhR wit...

  4. Activation of the aryl hydrocarbon receptor suppresses sensitization in a mouse peanut allergy model.

    Science.gov (United States)

    Schulz, V J; Smit, J J; Willemsen, K J; Fiechter, D; Hassing, I; Bleumink, R; Boon, L; van den Berg, M; van Duursen, M B M; Pieters, R H H

    2011-10-01

    Food allergy is an increasing health problem in Western countries. Previously, it has been shown that the intensity of food allergic reactions can be regulated by regulatory T (T(reg)) cells. In addition, it has been shown that activation of the aryl hydrocarbon receptor (AhR) regulates T-cell responses by induction of T(reg) cells. Therefore, we hypothesized that activation of the AhR pathway can suppress development of food allergic responses through the induction of T(reg) cells. This was investigated by using a mouse model for peanut allergy. C3H/HeOuJ mice (AhR(b)(-2)) were sensitized to peanut by administering peanut extract (PE) by gavage in the presence of cholera toxin and were treated with the prototypical AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (0.6, 1.7, 5, and 15 μg/kg body weight) on days 3 and 11 orally. The functional role of CD4(+)CD25(+)Foxp3(+) T(reg) cells was investigated by depleting these cells with anti-CD25 mAb during sensitization to PE. TCDD treatment dose dependently suppressed sensitization to peanut (PE-specific IgE, IgG1, and IgG2a and PE-induced IL-5, IL-10, and IL-13, respectively). The percentage, but not the number, of CD4(+)CD25(+)Foxp3(+) T(reg) cells dose dependently increased by AhR activation in both spleen and mesenteric lymph nodes. Depletion of CD4(+)CD25(+)Foxp3(+) T(reg) cells markedly reversed the suppressive effect of TCDD on PE-specific antibody levels and PE-induced IL-5, IL-10, and IL-13 cytokine production. Present data demonstrate for the first time that activation of the AhR by TCDD suppressed the development of Th2-mediated food allergic responses. A functional shift within the CD4(+) cell population toward CD4(+)CD25(+)Foxp3(+) T(reg) cells appeared to underlie this effect. This suggests that the AhR pathway might provide potential therapeutic targets to treat food allergic diseases.

  5. 6-Formylindolo[3,2-b]Carbazole Accelerates Skin Wound Healing via Activation of ERK, but Not Aryl Hydrocarbon Receptor.

    Science.gov (United States)

    Morino-Koga, Saori; Uchi, Hiroshi; Mitoma, Chikage; Wu, Zhouwei; Kiyomatsu, Mari; Fuyuno, Yoko; Nagae, Konosuke; Yasumatsu, Mao; Suico, Mary Ann; Kai, Hirofumi; Furue, Masutaka

    2017-10-01

    Wound healing is an elaborate process composed of overlapping phases, such as proliferation and remodeling, and is delayed in several circumstances, including diabetes. Although several treatment strategies for chronic wounds, such as growth factors, have been applied, further alternatives are required. The skin, especially keratinocytes, is continually exposed to UV rays, which impairs wound healing. 6-Formylindolo[3,2-b]carbazole (FICZ) is a tryptophan photoproduct formed by UV exposure, indicating that FICZ might be one of the effectors of UV radiation. In contrast, treatment with tryptophan, the precursor for FICZ, promoted wound closure in keratinocytes. Therefore, the aim of our study was to determine the role of FICZ in wound healing. Here we showed that FICZ enhanced keratinocyte migration through mitogen-activated protein kinase/extracellular signal-regulated kinase activation, and promoted wound healing in various mouse models, including db/db mice, which exhibit wound healing impairments because of type 2 diabetes. Moreover, FICZ, the endogenous ligand of an aryl hydrocarbon receptor, accelerated migration even in the aryl hydrocarbon receptor knockdown condition and also promoted wound healing in DBA/2 mice, bearing a low-affinity aryl hydrocarbon receptor, suggesting that FICZ enhanced keratinocyte migration in a mitogen-activated protein kinase/extracellular signal-regulated kinase-dependent, but aryl hydrocarbon receptor-independent, manner. The function of FICZ might indicate the possibility of its clinical use for intractable chronic wounds. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  6. An unusual case of an ACTH-secreting macroadenoma with a germline variant in the aryl hydrocarbon receptor-interacting protein (AIP) gene

    DEFF Research Database (Denmark)

    Dinesen, Pia T; Dal, Jakob; Gabrovska, Plamena

    2015-01-01

    UNLABELLED: A patient of Cushing's disease (CD) characterized by a large tumor and only subtle symptoms of hormonal hypersecretion was examined. The patient had a germline variant in the aryl hydrocarbon receptor-interacting protein (AIP) gene. A 50-year-old male presenting with headache...

  7. TGF-beta1 signaling plays a dominant role in the crosstalk between TGF-beta1 and the aryl hydrocarbon receptor ligand in prostate epithelial cells

    Czech Academy of Sciences Publication Activity Database

    Staršíchová, Andrea; Hrubá, E.; Slabáková, Eva; Pernicová, Zuzana; Procházková, Jiřina; Pěnčíková, K.; Šeda, Václav; Kabátková, Markéta; Vondráček, Jan; Kozubík, Alois; Machala, M.; Souček, Karel

    2012-01-01

    Roč. 24, č. 8 (2012), s. 1665-1676 ISSN 0898-6568 R&D Projects: GA ČR(CZ) GA310/07/0961 Institutional research plan: CEZ:AV0Z50040702 Keywords : transforming growth factor-beta * aryl hydrocarbon receptor ligand * prostate epithelial cells Subject RIV: BO - Biophysics Impact factor: 4.304, year: 2012

  8. Aryl hydrocarbon receptor (AhR) inducers and estrogen receptor (ER) activities in surface sediments of Three Gorges Reservoir, China evaluated with in vitro cell bioassays

    NARCIS (Netherlands)

    Wang, J.; Bovee, T.F.H.; Bi, Y.; Bernhöft, S.; Schramm, K.W.

    2014-01-01

    Two types of biological tests were employed for monitoring the toxicological profile of sediment cores in the Three Gorges Reservoir (TGR), China. In the present study, sediments collected in June 2010 from TGR were analyzed for estrogen receptor (ER)- and aryl hydrocarbon receptor (AhR)-mediated

  9. Malassezia-derived indoles activate the aryl hydrocarbon receptor and inhibit Toll-like receptor-induced maturation in monocyte-derived dendritic cells.

    NARCIS (Netherlands)

    Vlachos, C.; Schulte, B.M.; Magiatis, P.; Adema, G.J.; Gaitanis, G.

    2012-01-01

    Background The aryl hydrocarbon receptor (AhR) is a nuclear receptor and transcriptional regulator with pleiotropic effects. The production of potent AhR ligands by Malassezia yeasts, such as indirubin, indolo[3,2-b]carbazole (ICZ), tryptanthrin and malassezin, has been associated with the

  10. Differential effects of indirubin and 2,3,7,8-tetrachlorodibenzo-p-dioxin on the aryl hydrocarbon receptor (AhR) signalling in liver progenitor cells

    Czech Academy of Sciences Publication Activity Database

    Procházková, Jiřina; Kozubík, Alois; Machala, M.; Vondráček, Jan

    2011-01-01

    Roč. 279, 1-3 (2011), s. 146-154 ISSN 0300-483X R&D Projects: GA ČR(CZ) GA524/06/0517 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : indirubin * aryl hydrocarbon receptor * plakoglobin Subject RIV: BO - Biophysics Impact factor: 3.681, year: 2011

  11. Activation of the aryl hydrocarbon receptor reduces the number of precursor and effector T cells, but preserves thymic CD4(+)CD25(+)Foxp3(+) regulatory T cells

    NARCIS (Netherlands)

    Schulz, V.J.; Smit, J.J.; Bol-Schoenmakers, M.; van Duursen, M.B.M.; van den Berg, M.; Pieters, R.H.H.

    2012-01-01

    Aryl hydrocarbon receptor (AhR) activation suppresses immune responses, including allergic sensitization, by increasing the percentage of regulatory (Treg) cells. Furthermore, AhR activation is known to affect thymic precursor T cells. However, the effect of AhR activation on intrathymic

  12. The aryl hydrocarbon receptor AhR links atopic dermatitis and air pollution via induction of the neurotrophic factor artemin.

    Science.gov (United States)

    Hidaka, Takanori; Ogawa, Eisaku; Kobayashi, Eri H; Suzuki, Takafumi; Funayama, Ryo; Nagashima, Takeshi; Fujimura, Taku; Aiba, Setsuya; Nakayama, Keiko; Okuyama, Ryuhei; Yamamoto, Masayuki

    2017-01-01

    Atopic dermatitis is increasing worldwide in correlation with air pollution. Various organic components of pollutants activate the transcription factor AhR (aryl hydrocarbon receptor). Through the use of AhR-CA mice, whose keratinocytes express constitutively active AhR and that develop atopic-dermatitis-like phenotypes, we identified Artn as a keratinocyte-specific AhR target gene whose product (the neurotrophic factor artemin) was responsible for epidermal hyper-innervation that led to hypersensitivity to pruritus. The activation of AhR via air pollutants induced expression of artemin, alloknesis, epidermal hyper-innervation and inflammation. AhR activation and ARTN expression were positively correlated in the epidermis of patients with atopic dermatitis. Thus, AhR in keratinocytes senses environmental stimuli and elicits an atopic-dermatitis pathology. We propose a mechanism of air-pollution-induced atopic dermatitis via activation of AhR.

  13. Malassezin, a novel agonist of the aryl hydrocarbon receptor from the yeast Malassezia furfur, induces apoptosis in primary human melanocytes.

    Science.gov (United States)

    Krämer, Hans-Joachim; Podobinska, Monika; Bartsch, Andrea; Battmann, Achim; Thoma, Wiebke; Bernd, August; Kummer, Wolfgang; Irlinger, Bernhard; Steglich, Wolfgang; Mayser, Peter

    2005-05-01

    Pityriasis versicolor is the most common skin mycosis in humans worldwide. Yeasts of the genus Malassezia, particularly M. furfur, a saprophyte occurring widely on human skin, are generally regarded as the causative agents. Pityriasis versicolor is often accompanied by a long-lasting depigmentation that persists even after successful antimycotic therapy. M. furfur is able to convert tryptophan into a variety of indole alkaloids, some of them showing biological properties that correlate well with certain clinical features of pityriasis versicolor. This suggests a possible role for these compounds in the depigmentation process. We now report that human melanocytes undergo apoptosis when exposed to the crude mixture of tryptophan metabolites from M. furfur. The active compound was identified as malassezin, previously isolated by us from the same source and characterized as an agonist of the aryl hydrocarbon (Ah) receptor. The compound could, therefore, contribute to the marked depigmentation observed during the course of pityriasis versicolor.

  14. Dioxin Toxicity In Vivo Results from an Increase in the Dioxin-Independent Transcriptional Activity of the Aryl Hydrocarbon Receptor

    Science.gov (United States)

    Céspedes, Miguel Angel; Galindo, Maximo Ibo; Couso, Juan Pablo

    2010-01-01

    The Aryl hydrocarbon receptor (Ahr) is the nuclear receptor mediating the toxicity of dioxins -widespread and persistent pollutants whose toxic effects include tumor promotion, teratogenesis, wasting syndrome and chloracne. Elimination of Ahr in mice eliminates dioxin toxicity but also produces adverse effects, some seemingly unrelated to dioxin. Thus the relationship between the toxic and dioxin-independent functions of Ahr is not clear, which hampers understanding and treatment of dioxin toxicity. Here we develop a Drosophila model to show that dioxin actually increases the in vivo dioxin-independent activity of Ahr. This hyperactivation resembles the effects caused by an increase in the amount of its dimerisation partner Ahr nuclear translocator (Arnt) and entails an increased transcriptional potency of Ahr, in addition to the previously described effect on nuclear translocation. Thus the two apparently different functions of Ahr, dioxin-mediated and dioxin-independent, are in fact two different levels (hyperactivated and basal, respectively) of a single function. PMID:21079739

  15. Regulation of estrogen sulfotransferase expression by confluence of MCF10A breast epithelial cells: role of the aryl hydrocarbon receptor.

    Science.gov (United States)

    Fu, Jiaqi; Fang, Hailin; Paulsen, Michelle; Ljungman, Mats; Kocarek, Thomas A; Runge-Morris, Melissa

    2011-11-01

    Estrogen sulfotransferase (SULT1E1) catalyzes the sulfonation of estrogens, which limits estrogen mitogenicity. We recently reported that SULT1E1 expression is low in preconfluent MCF10A human breast epithelial cells but increases when the cells become confluent. Pulse-chase labeling experiments with 5-bromouridine demonstrated that the confluence-mediated increase in SULT1E1 expression was due to increased mRNA synthesis. Because aryl hydrocarbon receptor (AhR) activation has been shown to suppress SULT1E1 expression and loss of cell-cell contact has been shown to activate the AhR in other cell types, we tested whether the confluence-associated changes in SULT1E1 expression were mediated by the AhR. Relative to confluent MCF10A cells, preconfluent cells had higher levels of CYP1A1 mRNA and greater activation of an AhR-responsive luciferase reporter, demonstrating that the AhR was active in the preconfluent cells. AhR and aryl hydrocarbon receptor nuclear translocator mRNA and protein levels were also higher in preconfluent than in confluent cultures. Treatment of preconfluent cells with the AhR antagonist, 3'-methoxy-4'-nitroflavone (MNF), or AhR knockdown significantly increased SULT1E1 expression. MCF10A cells stably transfected with a luciferase reporter containing ∼7 kilobases of the SULT1E1 5'-flanking region showed both MNF- and confluence-inducible luciferase expression. Preconfluent cells transiently transfected with the reporter showed both MNF treatment- and AhR knockdown-mediated luciferase induction, but mutation of a computationally predicted dioxin response element (DRE) at nucleotide (nt) -3476 did not attenuate these effects. These results demonstrate that SULT1E1 expression in MCF10A cells is transcriptionally regulated by confluence through a suppressive action of the AhR, which is not mediated through a DRE at nt -3476.

  16. Identification of cinnabarinic acid as a novel endogenous aryl hydrocarbon receptor ligand that drives IL-22 production.

    Directory of Open Access Journals (Sweden)

    Margaret M Lowe

    Full Text Available The aryl hydrocarbon receptor (AHR binds to environmental toxicants including synthetic halogenated aromatic hydrocarbons and is involved in a diverse array of biological processes. Recently, the AHR was shown to control host immunity by affecting the balance between inflammatory T cells that produce IL-17 (Th17 and IL-22 versus regulatory T cells (Treg involved in tolerance. While environmental AHR ligands can mediate this effect, endogenous ligands are likely to be more relevant in host immune responses. We investigated downstream metabolites of tryptophan as potential AHR ligands because (1 tryptophan metabolites have been implicated in regulating the balance between Th17 and Treg cells and (2 many of the AHR ligands identified thus far are derivatives of tryptophan. We characterized the ability of tryptophan metabolites to bind and activate the AHR and to increase IL-22 production in human T cells. We report that the tryptophan metabolite, cinnabarinic acid (CA, is an AHR ligand that stimulates the differentiation of human and mouse T cells producing IL-22. We compare the IL-22-stimulating activity of CA to that of other tryptophan metabolites and define stimulation conditions that lead to CA production from immune cells. Our findings link tryptophan metabolism to AHR activation and define a novel endogenous AHR agonist with potentially broad biological functions.

  17. Identification of cinnabarinic acid as a novel endogenous aryl hydrocarbon receptor ligand that drives IL-22 production.

    Science.gov (United States)

    Lowe, Margaret M; Mold, Jeff E; Kanwar, Bittoo; Huang, Yong; Louie, Alexander; Pollastri, Michael P; Wang, Cuihua; Patel, Gautam; Franks, Diana G; Schlezinger, Jennifer; Sherr, David H; Silverstone, Allen E; Hahn, Mark E; McCune, Joseph M

    2014-01-01

    The aryl hydrocarbon receptor (AHR) binds to environmental toxicants including synthetic halogenated aromatic hydrocarbons and is involved in a diverse array of biological processes. Recently, the AHR was shown to control host immunity by affecting the balance between inflammatory T cells that produce IL-17 (Th17) and IL-22 versus regulatory T cells (Treg) involved in tolerance. While environmental AHR ligands can mediate this effect, endogenous ligands are likely to be more relevant in host immune responses. We investigated downstream metabolites of tryptophan as potential AHR ligands because (1) tryptophan metabolites have been implicated in regulating the balance between Th17 and Treg cells and (2) many of the AHR ligands identified thus far are derivatives of tryptophan. We characterized the ability of tryptophan metabolites to bind and activate the AHR and to increase IL-22 production in human T cells. We report that the tryptophan metabolite, cinnabarinic acid (CA), is an AHR ligand that stimulates the differentiation of human and mouse T cells producing IL-22. We compare the IL-22-stimulating activity of CA to that of other tryptophan metabolites and define stimulation conditions that lead to CA production from immune cells. Our findings link tryptophan metabolism to AHR activation and define a novel endogenous AHR agonist with potentially broad biological functions.

  18. Aryl Hydrocarbon Receptor Antagonists Mitigate the Effects of Dioxin on Critical Cellular Functions in Differentiating Human Osteoblast-Like Cells

    Directory of Open Access Journals (Sweden)

    Chawon Yun

    2018-01-01

    Full Text Available The inhibition of bone healing in humans is a well-established effect associated with cigarette smoking, but the underlying mechanisms are still unclear. Recent work using animal cell lines have implicated the aryl hydrocarbon receptor (AhR as a mediator of the anti-osteogenic effects of cigarette smoke, but the complexity of cigarette smoke mixtures makes understanding the mechanisms of action a major challenge. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD, dioxin is a high-affinity AhR ligand that is frequently used to investigate biological processes impacted by AhR activation. Since there are dozens of AhR ligands present in cigarette smoke, we utilized dioxin as a prototype ligand to activate the receptor and explore its effects on pro-osteogenic biomarkers and other factors critical to osteogenesis using a human osteoblast-like cell line. We also explored the capacity for AhR antagonists to protect against dioxin action in this context. We found dioxin to inhibit osteogenic differentiation, whereas co-treatment with various AhR antagonists protected against dioxin action. Dioxin also negatively impacted cell adhesion with a corresponding reduction in the expression of integrin and cadherin proteins, which are known to be involved in this process. Similarly, the dioxin-mediated inhibition of cell migration correlated with reduced expression of the chemokine receptor CXCR4 and its ligand, CXCL12, and co-treatment with antagonists restored migratory capacity. Our results suggest that AhR activation may play a role in the bone regenerative response in humans exposed to AhR activators, such as those present in cigarette smoke. Given the similarity of our results using a human cell line to previous work done in murine cells, animal models may yield data relevant to the human setting. In addition, the AhR may represent a potential therapeutic target for orthopedic patients who smoke cigarettes, or those who are exposed to secondhand smoke or other

  19. Effect of dioxins on regulation of tyrosine hydroxylase gene expression by aryl hydrocarbon receptor: a neurotoxicology study

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    Akahoshi Eiichi

    2009-06-01

    Full Text Available Abstract Background Dioxins and related compounds are suspected of causing neurological disruption. Epidemiological studies indicated that exposure to these compounds caused neurodevelopmental disturbances such as learning disability and attention deficit hyperactivity disorder, which are thought to be closely related to dopaminergic dysfunction. Although the molecular mechanism of their actions has not been fully investigated, a major participant in the process is aryl hydrocarbon receptor (AhR. This study focused on the effect of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD exposure on the regulation of TH, a rate-limiting enzyme of dopamine synthesis, gene expression by AhR. Methods N2a-Rβ cells were established by transfecting murine neuroblastoma Neuro2a with the rat AhR cDNA. TH expression induced by TCDD was assessed by RT-PCR and Western blotting. Participation of AhR in TCDD-induced TH gene expression was confirmed by suppressing AhR expression using the siRNA method. Catecholamines including dopamine were measured by high-performance liquid chromatography. A reporter gene assay was used to identify regulatory motifs in the promoter region of TH gene. Binding of AhR with the regulatory motif was confirmed by an electrophoretic mobility shift assay (EMSA. Results Induction of TH by TCDD through AhR activation was detected at mRNA and protein levels. Induced TH protein was functional and its expression increased dopamine synthesis. The reporter gene assay and EMSA indicated that AhR directly regulated TH gene expression. Regulatory sequence called aryl hydrocarbon receptor responsive element III (AHRE-III was identified upstream of the TH gene from -285 bp to -167 bp. Under TCDD exposure, an AhR complex was bound to AHRE-III as well as the xenobiotic response element (XRE, though AHRE-III was not identical to XRE, the conventional AhR-binding motif. Conclusion Our results suggest TCDD directly regulate the dopamine system by TH gene

  20. Tissue-specific expression of aryl hydrocarbon receptor and putative developmental regulatory modules in Baltic salmon yolk-sac fry

    International Nuclear Information System (INIS)

    Vuori, Kristiina A.; Nordlund, Eija; Kallio, Jenny; Salakoski, Tapio; Nikinmaa, Mikko

    2008-01-01

    The aryl hydrocarbon receptor (AhR) is an ancient protein that is conserved in vertebrates and invertebrates, indicating its important function throughout evolution. AhR has been studied largely because of its role in toxicology-gene expression via AhR is induced by many aromatic hydrocarbons in mammals. Recently, however, it has become clear that AhR is involved in various aspects of development such as cell proliferation and differentiation, and cell motility and migration. The mechanisms by which AhR regulates these various functions remain poorly understood. Across-species comparative studies of AhR in invertebrates, non-mammalian vertebrates and mammals may help to reveal the multiple functions of AhR. Here, we have studied AhR during larval development of Baltic salmon (Salmon salar). Our results indicate that AhR protein is expressed in nervous system, liver and muscle tissues. We also present putative regulatory modules and module-matching genes, produced by chromatin immunoprecipitation (ChIP) cloning and in silico analysis, which may be associated with evolutionarily conserved functions of AhR during development. For example, the module NFKB-AHRR-CREB found from salmon ChIP sequences is present in human ULK3 (regulating formation of granule cell axons in mouse and axon outgrowth in Caernohabditis elegans) and SRGAP1 (GTPase-activating protein involved in the Slit/Robo pathway) promoters. We suggest that AhR may have an evolutionarily conserved role in neuronal development and nerve cell targeting, and in Wnt signaling pathway

  1. Tissue-specific expression of aryl hydrocarbon receptor and putative developmental regulatory modules in Baltic salmon yolk-sac fry

    Energy Technology Data Exchange (ETDEWEB)

    Vuori, Kristiina A. [Centre of Excellence in Evolutionary Genetics and Physiology, Department of Biology, University of Turku, FI-20014 Turku (Finland)], E-mail: kristiina.vuori@utu.fi; Nordlund, Eija [Department of Information Technology, University of Turku, and Turku Centre for Computer Science (TUCS), FI-20014 Turku (Finland); Kallio, Jenny [Centre of Excellence in Evolutionary Genetics and Physiology, Department of Biology, University of Turku, FI-20014 Turku (Finland); Salakoski, Tapio [Department of Information Technology, University of Turku, and Turku Centre for Computer Science (TUCS), FI-20014 Turku (Finland); Nikinmaa, Mikko [Centre of Excellence in Evolutionary Genetics and Physiology, Department of Biology, University of Turku, FI-20014 Turku (Finland)

    2008-04-08

    The aryl hydrocarbon receptor (AhR) is an ancient protein that is conserved in vertebrates and invertebrates, indicating its important function throughout evolution. AhR has been studied largely because of its role in toxicology-gene expression via AhR is induced by many aromatic hydrocarbons in mammals. Recently, however, it has become clear that AhR is involved in various aspects of development such as cell proliferation and differentiation, and cell motility and migration. The mechanisms by which AhR regulates these various functions remain poorly understood. Across-species comparative studies of AhR in invertebrates, non-mammalian vertebrates and mammals may help to reveal the multiple functions of AhR. Here, we have studied AhR during larval development of Baltic salmon (Salmon salar). Our results indicate that AhR protein is expressed in nervous system, liver and muscle tissues. We also present putative regulatory modules and module-matching genes, produced by chromatin immunoprecipitation (ChIP) cloning and in silico analysis, which may be associated with evolutionarily conserved functions of AhR during development. For example, the module NFKB-AHRR-CREB found from salmon ChIP sequences is present in human ULK3 (regulating formation of granule cell axons in mouse and axon outgrowth in Caernohabditis elegans) and SRGAP1 (GTPase-activating protein involved in the Slit/Robo pathway) promoters. We suggest that AhR may have an evolutionarily conserved role in neuronal development and nerve cell targeting, and in Wnt signaling pathway.

  2. A role of aryl hydrocarbon receptor in the antiandrogenic effects of polycyclic aromatic hydrocarbons in LNCaP human prostate carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Kizu, Ryoichi; Okamura, Kazumasa; Toriba, Akira; Hayakawa, Kazuichi [Graduate School of Natural Science and Technology, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934 (Japan); Kakishima, Hiroshi [Research Planning Department, Eiken Chemical Co. Ltd., 5-26-20 Oji, Kita-ku, Tokyo 114-0002 (Japan); Mizokami, Atsushi [School of Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641 (Japan); Burnstein, Kerry L. [Department of Molecular and Cellular Pharmacology, University of Miami School of Medicine, FL 33101, Miami (United States)

    2003-06-01

    The role of aryl hydrocarbon receptor (AhR) on the antiandrogenic effects of polycyclic aromatic hydrocarbons (PAHs) was studied in LNCaP cells. The PAHs used in this study were chrysene (Chr), benzo[k]fluoranthene (BkF), benzo[a]pyrene (BaP), anthracene (Ant) and pyrene (Pyr). Chr, BkF and BaP acted as AhR agonists in LNCaP cells, while Ant and Pyr did not. The antiandrogenic effects of the PAHs were evaluated on the basis of regulation of prostate-specific antigen (PSA) mRNA and protein levels by 5{alpha}-dihydrotestosterone (DHT). Chr, BkF and BaP exhibited an antiandrogenic effect, but Ant and Pyr did not. {alpha}-Naphthoflavone ({alpha}-NF), an AhR antagonist, reversed the antiandrogen action of Chr, BkF and BaP, suggesting a requirement for activated AhR. The antiandrogenic PAHs did not significantly decrease androgen receptor (AR) levels or cellular DHT concentrations. Gel mobility shift assays revealed that Chr, BkF and BaP inhibited the binding of AR in nuclear extracts to oligonucleotide probes containing the AR-responsive element (ARE), whereas Ant and Pyr had no effect. The antiandrogenic PAHs elevated mRNA levels of c-fos and c-jun. Since activator protein-1 (AP-1), a heterodimer of c-jun and c-fos proteins, is known to inhibit binding of AR to ARE by protein-protein interaction with AR, the findings in the present study suggest a possible involvement of AP-1 in the antiandrogenic effects of PAHs acting as AhR agonists. These results suggest that AhR can stimulate AP-1 expression resulting in inhibition of the binding of AR to ARE in the transcription regulatory region of target genes such as PSA. (orig.)

  3. Essential oils of culinary herbs and spices display agonist and antagonist activities at human aryl hydrocarbon receptor AhR.

    Science.gov (United States)

    Bartoňková, Iveta; Dvořák, Zdeněk

    2018-01-01

    Essential oils (EOs) of culinary herbs and spices are used to flavor, color and preserve foods and drinks. Dietary intake of EOs is significant, deserving an attention of toxicologists. We examined the effects of 31 EOs of culinary herbs and spices on the transcriptional activity of human aryl hydrocarbon receptor (AhR), which is a pivotal xenobiotic sensor, having also multiple roles in human physiology. Tested EOs were sorted out into AhR-inactive ones (14 EOs) and AhR-active ones, including full agonists (cumin, jasmine, vanilla, bay leaf), partial agonists (cloves, dill, thyme, nutmeg, oregano) and antagonists (tarragon, caraway, turmeric, lovage, fennel, spearmint, star anise, anise). Major constituents (>10%) of AhR-active EOs were studied in more detail. We identified AhR partial agonists (carvacrol, ligustilide, eugenol, eugenyl acetate, thymol, ar-turmerone) and antagonists (trans-anethole, butylidine phtalide, R/S-carvones, p-cymene), which account for AhR-mediated activities of EOs of fennel, anise, star anise, caraway, spearmint, tarragon, cloves, dill, turmeric, lovage, thyme and oregano. We also show that AhR-mediated effects of some individual constituents of EOs differ from those manifested in mixtures. In conclusion, EOs of culinary herbs and spices are agonists and antagonists of human AhR, implying a potential for food-drug interactions and interference with endocrine pathways. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Gene-environment interactions in male reproductive health: special reference to the aryl hydrocarbon receptor signaling pathway

    Directory of Open Access Journals (Sweden)

    Leon J S Brokken

    2014-02-01

    Full Text Available Over the last few decades, there have been numerous reports of adverse effects on the reproductive health of wildlife and laboratory animals caused by exposure to endocrine disrupting chemicals (EDCs. The increasing trends in human male reproductive disorders and the mounting evidence for causative environmental factors have therefore sparked growing interest in the health threat posed to humans by EDCs, which are substances in our food, environment and consumer items that interfere with hormone action, biosynthesis or metabolism, resulting in disrupted tissue homeostasis or reproductive function. The mechanisms of EDCs involve a wide array of actions and pathways. Examples include the estrogenic, androgenic, thyroid and retinoid pathways, in which the EDCs may act directly as agonists or antagonists, or indirectly via other nuclear receptors. Dioxins and dioxin-like EDCs exert their biological and toxicological actions through activation of the aryl hydrocarbon-receptor, which besides inducing transcription of detoxifying enzymes also regulates transcriptional activity of other nuclear receptors. There is increasing evidence that genetic predispositions may modify the susceptibility to adverse effects of toxic chemicals. In this review, potential consequences of hereditary predisposition and EDCs are discussed, with a special focus on the currently available publications on interactions between dioxin and androgen signaling.

  5. Improvement of Chicken Primordial Germ Cell Maintenance In Vitro by Blockade of the Aryl Hydrocarbon Receptor Endogenous Activity.

    Science.gov (United States)

    Pérez Sáez, Juan M; Bussmann, Leonardo E; Barañao, J Lino; Bussmann, Ursula A

    2016-06-01

    Primordial germ cells (PGCs) are the undifferentiated progenitors of gametes. Germline competent PGCs can be developed as a cell-based system for genetic modification in chickens, which provides a valuable tool for transgenic technology with both research and industrial applications. This implies manipulation of PGCs, which, in recent years, encouraged a lot of research focused on the study of PGCs and the way of improving their culture. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that besides mediating toxic responses to environmental contaminants plays pivotal physiological roles in various biological processes. Since a novel compound that acts as an antagonist of this receptor has been reported to promote expansion of hematopoietic stem cells, we conducted the present study with the aim of determining whether addition of an established AHR antagonist to the standard culture medium used nowadays for in vitro chicken PGCs culture improves ex vivo expansion. We have found that addition of α-naphthoflavone in culture medium promotes the amplification of undifferentiated cells and that this effect is exerted by the blockade of AHR action. Our results constitute the first report of the successful use of a readily available AHR antagonist to improve avian PGCs expansion, and they further extend the knowledge of the effects of AHR modulation in undifferentiated cells.

  6. Estrogen receptor-α and aryl hydrocarbon receptor involvement in the actions of botanical estrogens in target cells

    Science.gov (United States)

    Gong, Ping; Madak-Erdogan, Zeynep; Flaws, Jodi A.; Shapiro, David J.; Katzenellenbogen, John A.; Katzenellenbogen, Benita S.

    2018-01-01

    Botanical estrogen (BE) dietary supplements are consumed by women as substitutes for loss of endogenous estrogens at menopause. To examine the roles of estrogen receptor α (ERα) and aryl hydrocarbon receptor (AhR) and their crosstalk in the actions of BEs, we studied gene regulation and proliferation responses to four widely used BEs, genistein, daidzein, and S-equol from soy, and liquiritigen from licorice root in breast cancer and liver cells. BEs and estradiol (E2), acting through ERα, stimulated proliferation, ERα chromatin binding and target-gene expression. BEs but not E2, acting through AhR, bound to xenobiotic response element-containing chromatin sites and enhanced AhR target-gene expression (CYP1A1, CYP1B1). While E2 and TCDD acted quite selectively through their respective receptors, BEs acted via both receptors, with their AhR activity moderated by negative crosstalk through ERα. Both ERα and AhR should be considered as mediators of the biology and pharmacology of BEs. PMID:27543265

  7. Activation of the Aryl Hydrocarbon Receptor during Different Critical Windows in Pregnancy Alters Mammary Epithelial Cell Proliferation and Differentiation

    Science.gov (United States)

    Lew, Betina J.; Collins, Loretta L.; O'Reilly, Michael A.; Lawrence, B. Paige

    2009-01-01

    Exposure to the aryl hydrocarbon receptor (AhR) agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during pregnancy causes severe defects in mammary gland development and function; however, the underlying mechanism remains unclear. Alterations in epithelial cell proliferation, differentiation, and apoptosis during pregnancy-related mammary development can lead to failed lactogenesis. To determine which of these processes are affected and at what time periods, we examined proliferation, differentiation and apoptosis in mammary glands following exposure to TCDD during early, mid or throughout pregnancy. Although AhR activation throughout pregnancy did not cause early involution, there was a 50% decrease in cell proliferation, which was observed as early as the sixth day of pregnancy (DP). TCDD treatment on the day of impregnation only reduced development and proliferation in early and mid-pregnancy, followed by partial recovery by DP17. However, when AhR activation was delayed to DP7, developmental impairment was not observed in mid-pregnancy, but became evident by DP17, whereas proliferation was reduced at all times. Thus, early exposure to TCDD was neither necessary nor sufficient to cause persistent defects in lactogenesis. These varying outcomes in mammary development due to exposure at different times in pregnancy suggest there are critical windows during which AhR activation impairs mammary epithelial cell proliferation and differentiation. PMID:19502548

  8. Expression of Aryl Hydrocarbon Hydroxylase Induction and Suppression of Tyrosine Aminotransferase Induction in Somatic-Cell Hybrids

    Science.gov (United States)

    Benedict, W. F.; Nebert, D. W.; Thompson, E. B.

    1972-01-01

    Aryl hydrocarbon hydroxylase activity is inducible in mouse 3T3 fibroblasts by benz[α]anthracene, whereas no detectable basal or inducible levels of this enzyme occur in rat-hepatoma tissue culture cells. Conversely, tyrosine aminotransferase activity is inducible in hepatoma cells by dexamethasone, whereas only low noninducible levels of this enzyme exist in 3T3 cells. In hybrids formed by fusion of these two parent lines, levels of inducible hydroxylase activity range from the same as, to more than 20-fold greater than, that in the 3T3 parent; aminotransferase levels remain very low and noninducible in all of these same hybrids. A majority of the 1S-chromosomal complement from each parent is retained in most of these hybrids. The kinetics of hydroxylase induction and degradation, responses of hydroxylase induction to actinomycin D and cycloheximide, and the relative thermolability of the control and induced activities are similar in the 3T3 parent and in the hybrids. Failure to inactivate any of the aminotransferase activity in the hybrids with antibody specific for the rat enzyme indicates that all of the basal noninducible aminotransferase activity is derived from the mouse 3T3 parent. Images PMID:4403306

  9. beta-TrCP inhibition reduces prostate cancer cell growth via upregulation of the aryl hydrocarbon receptor.

    Directory of Open Access Journals (Sweden)

    Udi Gluschnaider

    2010-02-01

    Full Text Available Prostate cancer is a common and heterogeneous disease, where androgen receptor (AR signaling plays a pivotal role in development and progression. The initial treatment for advanced prostate cancer is suppression of androgen signaling. Later on, essentially all patients develop an androgen independent stage which does not respond to anti hormonal treatment. Thus, alternative strategies targeting novel molecular mechanisms are required. beta-TrCP is an E3 ligase that targets various substrates essential for many aspects of tumorigenesis.Here we show that beta-TrCP depletion suppresses prostate cancer and identify a relevant growth control mechanism. shRNA targeted against beta-TrCP reduced prostate cancer cell growth and cooperated with androgen ablation in vitro and in vivo. We found that beta-TrCP inhibition leads to upregulation of the aryl hydrocarbon receptor (AhR mediating the therapeutic effect. This phenomenon could be ligand independent, as the AhR ligand 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD did not alter prostate cancer cell growth. We detected high AhR expression and activation in basal cells and atrophic epithelial cells of human cancer bearing prostates. AhR expression and activation is also significantly higher in tumor cells compared to benign glandular epithelium.Together these observations suggest that AhR activation may be a cancer counteracting mechanism in the prostate. We maintain that combining beta-TrCP inhibition with androgen ablation could benefit advanced prostate cancer patients.

  10. Toward Understanding the Role of Aryl Hydrocarbon Receptor in the Immune System: Current Progress and Future Trends

    Directory of Open Access Journals (Sweden)

    Hamza Hanieh

    2014-01-01

    Full Text Available The immune system is regulated by distinct signaling pathways that control the development and function of the immune cells. Accumulating evidence suggest that ligation of aryl hydrocarbon receptor (Ahr, an environmentally responsive transcription factor, results in multiple cross talks that are capable of modulating these pathways and their downstream responsive genes. Most of the immune cells respond to such modulation, and many inflammatory response-related genes contain multiple xenobiotic-responsive elements (XREs boxes upstream. Active research efforts have investigated the physiological role of Ahr in inflammation and autoimmunity using different animal models. Recently formed paradigm has shown that activation of Ahr by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or 3,3′-diindolylmethane (DIM prompts the differentiation of CD4+Foxp3+ regulatory T cells (Tregs and inhibits T helper (Th-17 suggesting that Ahr is an innovative therapeutic strategy for autoimmune inflammation. These promising findings generate a basis for future clinical practices in humans. This review addresses the current knowledge on the role of Ahr in different immune cell compartments, with a particular focus on inflammation and autoimmunity.

  11. Constitutive Expression of Aryl Hydrocarbon Receptor in Keratinocytes Causes Inflammatory Skin Lesions

    OpenAIRE

    Tauchi, Masafumi; Hida, Azumi; Negishi, Takaaki; Katsuoka, Fumiki; Noda, Shuhei; Mimura, Junsei; Hosoya, Tomonori; Yanaka, Akinori; Aburatani, Hiroyuki; Fujii-Kuriyama, Yoshiaki; Motohashi, Hozumi; Yamamoto, Masayuki

    2005-01-01

    Occupational and environmental exposure to polycyclic aromatic hydrocarbons (PAHs) has been suggested to provoke inflammatory and/or allergic disorders, including asthma, rhinitis, and dermatitis. The molecular mechanisms of this PAH-mediated inflammation remain to be clarified. Previous studies implied the involvement of PAHs as irritants and allergens, with the reactive oxygen species generated from the oxygenated PAHs believed to be an exacerbating factor. It is also possible that PAHs con...

  12. Water exposure assessment of aryl hydrocarbon receptor agonists in Three Gorges Reservoir, China using SPMD-based virtual organisms.

    Science.gov (United States)

    Wang, Jingxian; Bernhöft, Silke; Pfister, Gerd; Schramm, Karl-Werner

    2014-10-15

    SPMD-based virtual organisms (VOs) were deployed at five to eight sites in the Three Gorges Reservoir (TGR), China for five periods in 2008, 2009 and 2011. The water exposure of aryl hydrocarbon receptor (AhR) agonists was assessed by the VOs. The chosen bioassay response for the extracts of the VOs, the induction of 7-ethoxyresorufin-O-deethylase (EROD) was assayed using a rat hepatoma cell line (H4IIE). The results show that the extracts from the VOs could induce AhR activity significantly, whereas the chemically derived 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalent (TEQcal) accounted for effects in the mixture. The levels of AhR agonists in VOs from upstream TGR were in general higher than those from downstream reservoir, indicating urbanization effect on AhR agonist pollution. The temporal variation showed that levels of AhR agonists in 2009 and 2011 were higher than those in 2008, and the potential non-additive effects in the area close to the dam were also obviously higher in 2009 and 2011 than in 2008, indicating big changes in the composition of pollutants in the area after water level reached a maximum of 175 m. Although the aqueous concentration of AhR agonists of 0.8-4.8 pg TCDDL(-1) in TGR was not alarming, the tendency of accumulating high concentration of AhR agonists in VO lipid and existence of possible synergism or antagonism in the water may exhibit a potential hazard to local biota being exposed to AhR agonists. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Targeting the aryl hydrocarbon receptor nuclear translocator complex with DMOG and Stemregenin 1 improves primitive hematopoietic stem cell expansion.

    Science.gov (United States)

    Jackson, Carlo Stephan; Durandt, Chrisna; Janse van Rensburg, Ilse; Praloran, Vincent; Brunet de la Grange, Philippe; Pepper, Michael Sean

    2017-05-01

    Culture conditions used for the expansion of hematopoietic stem and progenitor cells (HSCs and HPCs, collectively HSPCs) should ideally favor the self renewal of long-term HSCs. At 20% O 2 , the synthesis of HIF-1α is balanced by its hydroxylation and proteasomal degradation. This favors HSPC differentiation, but can be prevented by culturing CD34+ cord blood cells in the presence of dimethyloxaloylglycine (DMOG). This differentiation may also be reduced by culturing the cells in the presence of Stemregenin 1, an antagonist of the aryl hydrocarbon receptor (AhR). The objective of this study was to investigate how hypoxia, DMOG and Stemregenin 1 might affect the expansion of HSPCs with the aim of identifying optimal conditions for expansion in culture. It was found that DMOG decreased proliferation but was effective in preserving the number of cells in the primitive hematopoietic sub-populations in vitro. The effect of DMOG was similar to hypoxia, although differences were observed with regard to the side population and CD34+ sub-populations. Stemregenin 1 on the other hand increased the size of the primitive as well as the other HSC sub-populations. The use of Stemregenin 1 with DMOG increased the proportion of primitive HSCs to 3.54% compared to 2.61% for Stemregenin 1 alone. In vivo engraftment studies confirmed these findings and showed that fewer cells (3710) are required for long-term engraftment when HSCs are grown in Stemregenin 1 together with hypoxia than in Stemregenin 1 under conditions of normoxia (13430). Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

  14. Omeprazole Attenuates Pulmonary Aryl Hydrocarbon Receptor Activation and Potentiates Hyperoxia-Induced Developmental Lung Injury in Newborn Mice.

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    Shivanna, Binoy; Zhang, Shaojie; Patel, Ananddeep; Jiang, Weiwu; Wang, Lihua; Welty, Stephen E; Moorthy, Bhagavatula

    2015-11-01

    Hyperoxia contributes to the development of bronchopulmonary dysplasia (BPD) in human preterm infants and a similar lung phenotype characterized by alveolar simplification in newborn mice. Omeprazole (OM) is a proton pump inhibitor that is used to treat humans with gastric acid related disorders. OM-mediated aryl hydrocarbon receptor (AhR) activation attenuates acute hyperoxic lung injury (HLI) in adult mice. Whether OM activates pulmonary AhR and protects C57BL/6J newborn mice against hyperoxia-induced developmental lung (alveolar and pulmonary vascular simplification, inflammation, and oxidative stress) injury (HDLI) is unknown. Therefore, we tested the hypothesis that OM will activate pulmonary AhR and mitigate HDLI in newborn mice. Newborn mice were treated daily with i.p. injections of OM at doses of 10 (OM10) or 25 (OM25) mg/kg while being exposed to air or hyperoxia (FiO2 of 85%) for 14 days, following which their lungs were harvested to determine alveolarization, pulmonary vascularization, inflammation, oxidative stress, vascular injury, and AhR activation. To our surprise, hyperoxia-induced alveolar and pulmonary vascular simplification, inflammation, oxidative stress, and vascular injury were augmented in OM25-treated animals. These findings were associated with attenuated pulmonary vascular endothelial growth factor receptor 2 expression and decreased pulmonary AhR activation in the OM25 group. We conclude that contrary to our hypothesis, OM decreases functional activation of pulmonary AhR and potentiates HDLI in newborn mice. These observations are consistent with our previous findings, which suggest that AhR activation plays a protective role in HDLI in newborn mice. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. Differential effects of omeprazole and lansoprazole enantiomers on aryl hydrocarbon receptor in human hepatocytes and cell lines.

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    Novotna, Aneta; Srovnalova, Alzbeta; Svecarova, Michaela; Korhonova, Martina; Bartonkova, Iveta; Dvorak, Zdenek

    2014-01-01

    Proton pump inhibitors omeprazole and lansoprazole contain chiral sulfur atom and they are administered as a racemate, i.e. equimolar mixture of S- and R-enantiomers. The enantiopure drugs esomeprazole and dexlansoprazole have been developed and introduced to clinical practice due to their improved clinical and therapeutic properties. Since omeprazole and lansoprazole are activators of aryl hydrocarbon receptor (AhR) and inducers of CYP1A genes, we examined their enantiospecific effects on AhR-CYP1A pathway in human cancer cells and primary human hepatocytes. We performed gene reporter assays for transcriptional activity of AhR, RT-PCR analyses for CYP1A1/2 mRNAs, western blots for CYP1A1/2 proteins and EROD assay for CYP1A1/2 catalytic activity. Lansoprazole and omeprazole enantiomers displayed differential effects on AhR-CYP1A1/2 pathway. In general, S-enantiomers were stronger activators of AhR and inducers of CYP1A genes as compared to R-enantiomers in lower concentrations, i.e. 1-10 µM for lansoprazole and 10-100 µM for omeprazole. In contrast, R-enantiomers were stronger AhR activators and CYP1A inducers than S-enantiomers in higher concentrations, i.e. 100 µM for lansoprazole and 250 µM for omeprazole. In conclusion, we provide the first evidence of enantiospecific effects of omeprazole and lansoprazole on AhR signaling pathway.

  16. Evaluation of sensitizers found in wastewater from paper recycling areas, and their activation of the aryl hydrocarbon receptor in vitro.

    Science.gov (United States)

    Terasaki, Masanori; Yasuda, Michiko; Shimoi, Kayoko; Jozuka, Kazuhiko; Makino, Masakazu; Shiraishi, Fujio; Nakajima, Daisuke

    2014-09-15

    The in vitro potential of sensitizers and related compounds (SRCs) originating from impurities in waste paper in activating the human aryl hydrocarbon receptor (AhR) α was assessed using yeast reporter gene as well as cytochrome P450 (CYP)1A1 and ethoxyresorufin O-deethylase (EROD) assays. In the yeast assay, eight compounds exhibited agonist activity, and their activity relative to β-naphthoflavone (BNF) ranged from 1.4 × 10(-4) to 8.3 × 10(-2), with the highest activity observed for benzyl 2-naphthyl ether (BNE). In the EROD assay, six compounds caused a more significant induction of CYP1A-dependent activity than did the vehicle control at 50 μM (ppaper recycling area was fractioned using solid-phase extraction (SPE) combined with a C18 disk and florisil cartridge. In gas chromatography-mass spectrometry (GC-MS) analysis, SRCs were detected in the first fraction, at a total concentration of 5.5 μg/L. This fraction also activated AhR, and its activity, expressed as a BNF equivalent value, was 0.42 nM in the yeast assay. The contribution ratio of active compounds accounted for up to 34% and 4.4% observed activity of the fraction and total samples, respectively. To our knowledge, this is the first study to show that paper industry-related compounds, namely aromatic sensitizers, activate AhR by using a yeast assay and HepG2 cells. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Fibroblast growth factor (Fgf) 21 is a novel target gene of the aryl hydrocarbon receptor (AhR)

    International Nuclear Information System (INIS)

    Cheng, Xingguo; Vispute, Saurabh G.; Liu, Jie; Cheng, Christine; Kharitonenkov, Alexei; Klaassen, Curtis D.

    2014-01-01

    The toxic effects of dioxins, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), mainly through activation of the aryl hydrocarbon receptor (AhR) are well documented. Fibroblast growth factor (Fgf) 21 plays critical roles in metabolic adaptation to fasting by increasing lipid oxidation and ketogenesis in the liver. The present study was performed to determine whether activation of the AhR induces Fgf21 expression. In mouse liver, TCDD increased Fgf21 mRNA in both dose- and time-dependent manners. In addition, TCDD markedly increased Fgf21 mRNA expression in cultured mouse and human hepatocytes. Moreover, TCDD increased mRNA (in liver) and protein levels (in both liver and serum) of Fgf21 in wild-type mice, but not in AhR-null mice. Chromatin immunoprecipitation assays showed that TCDD increased AhR protein binding to the Fgf21 promoter (− 105/+ 1 base pair). Fgf21-null mice administered 200 μg/kg of TCDD died within 20 days, whereas wild-type mice receiving the same treatment were still alive at one month after administration. This indicates that TCDD-induced Fgf21 expression protects against TCDD toxicity. Diethylhexylphthalate (DEHP) pretreatment attenuated TCDD-induced Fgf21 expression in mouse liver and white adipose tissue, which may explain a previous report that DEHP pretreatment decreases TCDD-induced wasting. In conclusion, Fgf21 appears to be a target gene of AhR-signaling pathway in mouse and human liver. - Highlights: • TCDD induced Fgf21 expression at both mRNA and protein levels. • Fgf21 induction by TCDD is AhR-dependent. • DEHP attenuated TCDD-induced Fgf21 expression

  18. Fibroblast growth factor (Fgf) 21 is a novel target gene of the aryl hydrocarbon receptor (AhR)

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Xingguo, E-mail: chengx@stjohns.edu [Department of Pharmaceutical Sciences, St. John' s University, 8000 Utopia Parkway, Queens, NY 11439 (United States); Vispute, Saurabh G. [Department of Pharmaceutical Sciences, St. John' s University, 8000 Utopia Parkway, Queens, NY 11439 (United States); Liu, Jie [Department of Internal Medicine, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160 (United States); Cheng, Christine; Kharitonenkov, Alexei [Lilly Research Laboratories, Division of Eli Lilly and Co., Indianapolis, IN 46285 (United States); Klaassen, Curtis D., E-mail: curtisklaassenphd@gmail.com [Department of Internal Medicine, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160 (United States)

    2014-07-01

    The toxic effects of dioxins, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), mainly through activation of the aryl hydrocarbon receptor (AhR) are well documented. Fibroblast growth factor (Fgf) 21 plays critical roles in metabolic adaptation to fasting by increasing lipid oxidation and ketogenesis in the liver. The present study was performed to determine whether activation of the AhR induces Fgf21 expression. In mouse liver, TCDD increased Fgf21 mRNA in both dose- and time-dependent manners. In addition, TCDD markedly increased Fgf21 mRNA expression in cultured mouse and human hepatocytes. Moreover, TCDD increased mRNA (in liver) and protein levels (in both liver and serum) of Fgf21 in wild-type mice, but not in AhR-null mice. Chromatin immunoprecipitation assays showed that TCDD increased AhR protein binding to the Fgf21 promoter (− 105/+ 1 base pair). Fgf21-null mice administered 200 μg/kg of TCDD died within 20 days, whereas wild-type mice receiving the same treatment were still alive at one month after administration. This indicates that TCDD-induced Fgf21 expression protects against TCDD toxicity. Diethylhexylphthalate (DEHP) pretreatment attenuated TCDD-induced Fgf21 expression in mouse liver and white adipose tissue, which may explain a previous report that DEHP pretreatment decreases TCDD-induced wasting. In conclusion, Fgf21 appears to be a target gene of AhR-signaling pathway in mouse and human liver. - Highlights: • TCDD induced Fgf21 expression at both mRNA and protein levels. • Fgf21 induction by TCDD is AhR-dependent. • DEHP attenuated TCDD-induced Fgf21 expression.

  19. PCB 126 and Other Dioxin-Like PCBs Specifically Suppress Hepatic PEPCK Expression via the Aryl Hydrocarbon Receptor

    Science.gov (United States)

    Zhang, Wenshuo; Sargis, Robert M.; Volden, Paul A.; Carmean, Christopher M.; Sun, Xiao J.; Brady, Matthew J.

    2012-01-01

    Dioxins and dioxin-like compounds encompass a group of structurally related heterocyclic compounds that bind to and activate the aryl hydrocarbon receptor (AhR). The prototypical dioxin is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a highly toxic industrial byproduct that incites numerous adverse physiological effects. Global commercial production of the structurally similar polychlorinated biphenyls (PCBs), however, commenced early in the 20th century and continued for decades; dioxin-like PCBs therefore contribute significantly to total dioxin-associated toxicity. In this study, PCB 126, the most potent dioxin-like PCB, was evaluated with respect to its direct effects on hepatic glucose metabolism using primary mouse hepatocytes. Overnight treatment with PCB 126 reduced hepatic glycogen stores in a dose-dependent manner. Additionally, PCB 126 suppressed forskolin-stimulated gluconeogenesis from lactate. These effects were independent of acute toxicity, as PCB 126 did not increase lactate dehydrogenase release nor affect lipid metabolism or total intracellular ATP. Interestingly, provision of cells with glycerol instead of lactate as the carbon source completely restored hepatic glucose production, indicating specific impairment in the distal arm of gluconeogenesis. In concordance with this finding, PCB 126 blunted the forskolin-stimulated increase in phosphoenolpyruvate carboxykinase (PEPCK) mRNA levels without affecting glucose-6-phosphatase expression. Myricetin, a putative competitive AhR antagonist, reversed the suppression of PEPCK induction by PCB 126. Furthermore, other dioxin-like PCBs demonstrated similar effects on PEPCK expression in parallel with their ability to activate AhR. It therefore appears that AhR activation mediates the suppression of PEPCK expression by dioxin-like PCBs, suggesting a role for these pollutants as disruptors of energy metabolism. PMID:22615911

  20. Aryl Hydrocarbon Receptor (AhR Modulates Cockroach Allergen-Induced Immune Responses through Active TGFβ1 Release

    Directory of Open Access Journals (Sweden)

    Yufeng Zhou

    2014-01-01

    Full Text Available Background. Aryl hydrocarbon receptor (AhR, a multifunctional regulator that senses and responds to environmental stimuli, plays a role in normal cell development and immune regulation. Recent evidence supports a significant link between environmental exposure and AhR in the development of allergic diseases. We sought to investigate whether AhR plays a role in mediating cockroach allergen-induced allergic immune responses. Methods. AhR expression in human lung fibroblasts from asthmatic and healthy individuals and in cockroach extract (CRE treated human lung fibroblasts (WI-38 was examined. The role of AhR in modulating CRE induced TGFβ1 production was investigated by using AhR agonist, TCDD, antagonist CH122319, and knockdown of AhR. The role of latent TGFβ1 binding protein-1 (LTBP1 in mediating TCDD induced active TGFβ1 release was also examined. Results. AhR expression was higher in airway fibroblasts from asthmatic subjects as compared to healthy controls. AhR in fibroblasts was activated by TCDD with an increased expression of cyp1a1 and cyp1b1. Increased AhR expression was observed in CRE-treated fibroblasts. Importantly, CRE induced TGFβ1 production in fibroblasts was significantly enhanced by TCDD but inhibited by CH122319. Reduced TGFβ1 production was further confirmed in fibroblasts with AhR knockdown. Moreover, AhR knockdown inhibited CRE induced fibroblast differentiation. Furthermore, TCDD induced active TGFβ1 release was significantly inhibited by LTBP1 knockdown. Conclusion. These results provide evidence for the role of AhR in modulating cockroach allergen-induced immune responses through controlling the active TGFβ1 release, suggesting a possible synergistic effect between exposure to allergens and environmental chemicals on the development of allergic diseases.

  1. PCB 126 and other dioxin-like PCBs specifically suppress hepatic PEPCK expression via the aryl hydrocarbon receptor.

    Directory of Open Access Journals (Sweden)

    Wenshuo Zhang

    Full Text Available Dioxins and dioxin-like compounds encompass a group of structurally related heterocyclic compounds that bind to and activate the aryl hydrocarbon receptor (AhR. The prototypical dioxin is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, a highly toxic industrial byproduct that incites numerous adverse physiological effects. Global commercial production of the structurally similar polychlorinated biphenyls (PCBs, however, commenced early in the 20(th century and continued for decades; dioxin-like PCBs therefore contribute significantly to total dioxin-associated toxicity. In this study, PCB 126, the most potent dioxin-like PCB, was evaluated with respect to its direct effects on hepatic glucose metabolism using primary mouse hepatocytes. Overnight treatment with PCB 126 reduced hepatic glycogen stores in a dose-dependent manner. Additionally, PCB 126 suppressed forskolin-stimulated gluconeogenesis from lactate. These effects were independent of acute toxicity, as PCB 126 did not increase lactate dehydrogenase release nor affect lipid metabolism or total intracellular ATP. Interestingly, provision of cells with glycerol instead of lactate as the carbon source completely restored hepatic glucose production, indicating specific impairment in the distal arm of gluconeogenesis. In concordance with this finding, PCB 126 blunted the forskolin-stimulated increase in phosphoenolpyruvate carboxykinase (PEPCK mRNA levels without affecting glucose-6-phosphatase expression. Myricetin, a putative competitive AhR antagonist, reversed the suppression of PEPCK induction by PCB 126. Furthermore, other dioxin-like PCBs demonstrated similar effects on PEPCK expression in parallel with their ability to activate AhR. It therefore appears that AhR activation mediates the suppression of PEPCK expression by dioxin-like PCBs, suggesting a role for these pollutants as disruptors of energy metabolism.

  2. Could Malassezia yeasts be implicated in skin carcinogenesis through the production of aryl-hydrocarbon receptor ligands?

    Science.gov (United States)

    Gaitanis, G; Velegraki, A; Magiatis, P; Pappas, P; Bassukas, I D

    2011-07-01

    Malassezia yeasts are found on the skin of all humans and many warm-blooded animals. In vitro they have the ability to synthesize potent ligands (indolo[3,2-b]carbazole, malassezin and indirubin) of the aryl-hydrocarbon receptor (AhR; synonym: dioxin receptor) when the sweat contained L-tryptophan is used as the single nitrogen source. The production of these AhR-ligands has been associated with pathogenic strains of a certain Malassezia species (Malassezia furfur) but recent evidence shows that this property is widely distributed in almost all currently known Malassezia species. AhR is associated with carcinogenesis and the potential connection of these ubiquitous skin symbionts, and putative pathogens, with skin neoplasia should be evaluated mainly focusing on mechanisms related to the distinctive ability of the yeast to produce potent AhR ligands. Synthesis of available pertinent data show a possible link between Malassezia produced AhR ligands and skin carcinogenesis, particularly of basal cell carcinoma (BCC). BCCs are almost exclusively observed in animal species colonized by Malassezia. In humans and animals there is overlapping in the skin regions colonized by this yeast and affected by BCC. The potent AhR ligands synthesized by pathogenic Malassezia strains could contribute to tumor promotion by: modification of the UV radiation carcinogenesis, alterations in the salvage/survival of initiated tumor cells, inhibition of cell senescence, interaction with vitamin D metabolism, promotion of immune tolerance and finally pro-carcinogenic modulation of cell cycle progression and apoptosis. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Aryl hydrocarbon receptor activation by 2,3,7,8-tetrachlorodibenzo-p-dioxin impairs human B lymphopoiesis

    International Nuclear Information System (INIS)

    Li, Jinpeng; Phadnis-Moghe, Ashwini S.; Crawford, Robert B.; Kaminski, Norbert E.

    2017-01-01

    The homeostasis of peripheral B cell compartment requires lifelong B lymphopoiesis from hematopoietic stem cells (HSC). As a result, the B cell repertoire is susceptible to disruptions of hematopoiesis. Increasing evidence, primarily from rodent models, shows that the aryl hydrocarbon receptor (AHR) regulates hematopoiesis. To study the effects of persistent AHR activation on human B cell development, a potent AHR agonist and known environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was utilized. An in vitro B cell development model system was established by co-culturing human cord blood-derived HSCs with irradiated human primary bone marrow stromal cells. Using this in vitro model, we found that TCDD significantly suppressed the total number of hematopoietic stem and progenitor cells (HSPC) in a concentration-dependent manner. Cell death analysis demonstrated that the decrease in cell number was not due to cytotoxicity by TCDD. In addition, TCDD markedly decreased CD34 expression on HSPCs. Structure-activity relationship studies using dioxin congeners demonstrated a correlation between the relative AHR binding affinity and the magnitude of decrease in the number of HSPCs and CD34 expression, suggesting that AHR mediates the observed TCDD-elicited changes in HSPCs. Moreover, a significant reduction in lineage committed B cell-derived from HSCs was observed in the presence of TCDD, indicating impairment of human B cell development. Similar effects of TCDD were observed regardless of the use of stromal cells in cultures indicating a direct effect of TCDD on HSCs. Collectively, we demonstrate that AHR activation by TCDD on human HSCs impairs early stages of human B lymphopoiesis.

  4. Impact of culture medium on maturation of bone marrow-derived murine dendritic cells via the aryl hydrocarbon receptor.

    Science.gov (United States)

    Ilchmann, Anne; Krause, Maren; Heilmann, Monika; Burgdorf, Sven; Vieths, Stefan; Toda, Masako

    2012-05-01

    The aryl hydrocarbon receptor (AhR) plays a role in modulating dendritic cell (DC) immunity. Iscove's modified Dulbecco's medium (IMDM) contains higher amounts of AhR ligands than RPMI1640 medium. Here, we examined the influence of AhR ligand-containing medium on the maturation and T-cell stimulatory capacity of bone marrow-derived murine dendritic cells (BMDCs). BMDCs generated in IMDM (BMDCs/IMDM) expressed higher levels of co-stimulatory and MHC class II molecules, and lower levels of pattern-recognition receptors, especially toll-like receptor (TLR) 2, TLR4, and scavenger receptor class A (SR-A), compared to BMDCs generated in RPMI1640 medium (BMDCs/RPMI). Cytokine responses against ligands of TLRs and antigen uptake mediated by SR-A were remarkably reduced in BMDCs/IMDM, whereas the T-cell stimulatory capacity of the cells was enhanced, compared to BMDCs/RPMI. The enhanced maturation of BMDCs/IMDM was attenuated in the presence of an AhR antagonist, indicating involvement of AhR in the maturation. Interestingly, BMDCs/IMDM induced Th2 and Th17 differentiation at low and high concentrations of antigen respectively, when co-cultured with CD4(+) T-cells from antigen-specific T-cell receptor transgenic mice. In contrast, BMDCs/RPMI induced Th1 differentiation predominantly in the co-culture. Taken together, optimal selection of medium seems necessary when studying BMDCs, depending on the target receptors on the cell surface of DCs and type of helper T-cells for the co-culture. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Breast cancer stem-like cells are inhibited by a non-toxic aryl hydrocarbon receptor agonist.

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    Gérald J Prud'homme

    2010-11-01

    Full Text Available Cancer stem cells (CSCs have increased resistance to cancer chemotherapy. They can be enriched as drug-surviving CSCs (D-CSCs by growth with chemotherapeutic drugs, and/or by sorting of cells expressing CSC markers such as aldehyde dehydrogenase-1 (ALDH. CSCs form colonies in agar, mammospheres in low-adherence cultures, and tumors following xenotransplantation in Scid mice. We hypothesized that tranilast, a non-toxic orally active drug with anti-cancer activities, would inhibit breast CSCs.We examined breast cancer cell lines or D-CSCs generated by growth of these cells with mitoxantrone. Tranilast inhibited colony formation, mammosphere formation and stem cell marker expression. Mitoxantrone-selected cells were enriched for CSCs expressing stem cell markers ALDH, c-kit, Oct-4, and ABCG2, and efficient at forming mammospheres. Tranilast markedly inhibited mammosphere formation by D-CSCs and dissociated formed mammospheres, at pharmacologically relevant concentrations. It was effective against D-CSCs of both HER-2+ and triple-negative cell lines. Tranilast was also effective in vivo, since it prevented lung metastasis in mice injected i.v. with triple-negative (MDA-MB-231 mitoxantrone-selected cells. The molecular targets of tranilast in cancer have been unknown, but here we demonstrate it is an aryl hydrocarbon receptor (AHR agonist and this plays a key role. AHR is a transcription factor activated by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, polycyclic aromatic hydrocarbons and other ligands. Tranilast induced translocation of the AHR to the nucleus and stimulated CYP1A1 expression (a marker of AHR activation. It inhibited binding of the AHR to CDK4, which has been linked to cell-cycle arrest. D-CSCs expressed higher levels of the AHR than other cells. Knockdown of the AHR with siRNA, or blockade with an AHR antagonist, entirely abrogated the anti-proliferative and anti-mammosphere activity of tranilast. Thus, the anti-cancer effects of

  6. Common commercial and consumer products contain activators of the aryl hydrocarbon (dioxin receptor.

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    Bin Zhao

    Full Text Available Activation of the Ah receptor (AhR by halogenated aromatic hydrocarbons (HAHs, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin, can produce a wide variety of toxic and biological effects. While recent studies have shown that the AhR can bind and be activated by structurally diverse chemicals, how widespread of these AhR agonists are in environmental, biological and synthetic materials remains to be determined. Using AhR-based assays, we demonstrate the presence of potent AhR agonists in a variety of common commercial and consumer items. Solvent extracts of paper, rubber and plastic products contain chemicals that can bind to and stimulate AhR DNA binding and/or AhR-dependent gene expression in hepatic cytosol, cultured cell lines, human epidermis and zebrafish embryos. In contrast to TCDD and other persistent dioxin-like HAHs, activation of AhR-dependent gene expression by these extracts was transient, suggesting that the agonists are metabolically labile. Solvent extracts of rubber products produce AhR-dependent developmental toxicity in zebrafish in vivo, and inhibition of expression of the metabolic enzyme CYP1A, significantly increased their toxic potency. Although the identity of the responsible AhR-active chemicals and their toxicological impact remain to be determined, our data demonstrate that AhR active chemicals are widely distributed in everyday products.

  7. Over-expression of AhR (aryl hydrocarbon receptor induces neural differentiation of Neuro2a cells: neurotoxicology study

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    Ishihara-Sugano Mitsuko

    2006-09-01

    Full Text Available Abstract Background Dioxins and related compounds are suspected of causing neurological disruption in human and experimental animal offspring following perinatal exposure during development and growth. The molecular mechanism(s of the actions in the brain, however, have not been fully investigated. A major participant in the process of the dioxin-toxicity is the dioxin receptor, namely the aryl hydrocarbon receptor (AhR. AhR regulates the transcription of diverse genes through binding to the xenobiotic-responsive element (XRE. Since the AhR has also been detected in various regions of the brain, the AhR may play a key role in the developmental neurotoxicity of dioxins. This study focused on the effect of AhR activation in the developing neuron. Methods The influence of the AhR on the developing neuron was assessed using the Neuro2a-AhR transfectant. The undifferentiated murine neuroblastoma Neuro2a cell line (ATCC was stably transfected with AhR cDNA and the established cell line was named N2a-Rα. The activation of exogenous AhR in N2a-Rα cells was confirmed using RNAi, with si-AhR suppressing the expression of exogenous AhR. The neurological properties of N2a-Rα based on AhR activation were evaluated by immunohistochemical analysis of cytoskeletal molecules and by RT-PCR analysis of mRNA expression of neurotransmitter-production related molecules, such as tyrosine hydroxylase (TH. Results N2a-Rα cells exhibited constant activation of the exogenous AhR. CYP1A1, a typical XRE-regulated gene, mRNA was induced without the application of ligand to the culture medium. N2a-Rα cells exhibited two significant functional features. Morphologically, N2a-Rα cells bore spontaneous neurites exhibiting axon-like properties with the localization of NF-H. In addition, cdc42 expression was increased in comparison to the control cell line. The other is the catecholaminergic neuron-like property. N2a-Rα cells expressed tyrosine hydroxylase (TH mRNA as a

  8. Differential cellular metabolite alterations in HaCaT cells caused by exposure to the aryl hydrocarbon receptor-binding polycyclic aromatic hydrocarbons chrysene, benzo[a]pyrene and dibenzo[a,l]pyrene

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    Sarah Potratz

    Full Text Available Polycyclic aromatic hydrocarbons (PAHs are ubiquitous in the human environment. Since they are present in crude oilfractions used for the production of rubber and plastics, consumers may come into direct dermal contacts with these compounds (e.g., via tool handles on a daily basis. Some individual PAHs are identified as genotoxic mutagens thereby prompting particular toxicological and environmental concern. Among this group, benzo[a]pyrene (BAP constitutes a model carcinogen which is also used as reference compound for risk assessment purposes. It acts as a strong agonist of the aryl hydrocarbon receptor (AHR and becomes metabolically activated toward mutagenic and carcinogenic intermediates by cytochrome P450-dependent monooxygenases (CYPs. While BAP has been exhaustively characterized with regard to its toxicological properties, there is much less information available for other PAHs. We treated an AHR-proficient immortal human keratinocyte cell line (i.e., HaCaT with three selected PAHs: BAP, chrysene (CRY and dibenzo[a,l]pyrene (DALP. Compound-mediated alterations of endogenous metabolites were investigated by an LC–MS/MS-based targeted approach. To examine AHR-dependent changes of the measured metabolites, AHR-deficient HaCaT knockdown cells (AHR-KD were used for comparison. Our results reveal that 24 metabolites are sufficient to separate the PAH-exposed cells from untreated controls by application of a multivariate model. Alterations in the metabolomics profiles caused by each PAH show influences on the energy and lipid metabolism of the cells indicating reduced tricarboxylic acid (TCA cycle activity and β-oxidation. Up-regulation of sphingomyelin levels after exposure to BAP and DALP point to pro-apoptotic processes caused by these two potent PAHs. Our results suggest that in vitro metabolomics can serve as tool to develop bioassays for application in hazard assessment. Keywords: Polycyclic aromatic hydrocarbons, Metabolomics, Aryl

  9. Are aryl hydrocarbon receptor and G-protein-coupled receptor 30 involved in the regulation of seasonal testis activity in photosensitive rodent-the bank vole (Myodes glareolus)?

    Science.gov (United States)

    Zarzycka, Marta; Gorowska-Wojtowicz, Ewelina; Tworzydlo, Waclaw; Klak, Aleksandra; Kozub, Klaudia; Hejmej, Anna; Bilinska, Barbara; Kotula-Balak, Malgorzata

    2016-08-01

    Within the reproductive system both aryl hydrocarbon receptor (AHR) and G-protein-coupled receptor 30 (GPR30) contribute to estrogen signaling and controlling of reproductive physiology. The specific question is whether and how AHR and GPR30 are involved in regulation of testis function in seasonally breeding rodents. Bank vole testes were obtained from animals reared under 18 hours light:6 hours dark (LD) and 6 hours light:18 hours dark (SD) conditions. Aryl hydrocarbon receptor and GPR30 expression were analyzed by quantitative reverse transcriptase-polymerase chain reaction, Western blot, and immunohistochemistry and/or immunofluorescent staining. In addition, the activity of enzymes involved in the intracellular signal transduction; extracellular signal-regulated kinase (ERK), protein kinase (PKA), matrix metalloproteinase 9 (MMP 9) and the concentrations of cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), and calcium (Ca(2+)) were examined by immunohistochemical, immunoenzymatic, and colorimetric assays, respectively. Aryl hydrocarbon receptor and GPR30 were expressed in testes of actively reproducing voles and regressed ones although their expression at the messenger RNA and AHR also at protein level appeared to be photoperiod-dependent. A specific cellular localization and expression of AHR and GPR30 correlated with the expression of ERK, PKA, and MMP 9. Moreover, we found robust differences in the levels of cAMP, cGMP, and Ca(2+) in testicular homogenates between LD and SD voles. In the testes of LD voles, the levels of second messengers were always higher compared to SD. In vole testis, AHR and GPR30 can induce signaling pathways that involve ERK, PKA, MMP 9 and cAMP, cGMP, Ca(2+). In addition, in AHR, signaling the engagement of both photoperiod and estrogens, whereas in GPR30, signaling only estrogens is reported. It is likely that in vole, because of a differential activity of signaling molecules, signal transduction via

  10. Aryl hydrocarbon receptor-dependent regulation of miR-196a expression controls lung fibroblast apoptosis but not proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Hecht, Emelia [Department of Medicine, McGill University, Montreal, Quebec (Canada); Zago, Michela [Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec (Canada); Sarill, Miles [Department of Medicine, McGill University, Montreal, Quebec (Canada); Rico de Souza, Angela [Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec (Canada); Gomez, Alvin; Matthews, Jason [Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON (Canada); Hamid, Qutayba; Eidelman, David H. [Department of Medicine, McGill University, Montreal, Quebec (Canada); Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec (Canada); Baglole, Carolyn J., E-mail: Carolyn.baglole@McGill.ca [Department of Medicine, McGill University, Montreal, Quebec (Canada); Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec (Canada)

    2014-11-01

    The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor implicated in the regulation of apoptosis and proliferation. Although activation of the AhR by xenobiotics such as dioxin inhibits the cell cycle and control apoptosis, paradoxically, AhR expression also promotes cell proliferation and survival independent of exogenous ligands. The microRNA (miRNA) miR-196a has also emerged as a regulator of proliferation and apoptosis but a relationship between the AhR and miR-196a is not known. Therefore, we hypothesized that AhR-dependent regulation of endogenous miR-196a expression would promote cell survival and proliferation. Utilizing lung fibroblasts from AhR deficient (AhR{sup −/−}) and wild-type (AhR{sup +/+}) mice, we show that there is ligand-independent regulation of miRNA, including low miR-196a in AhR{sup −/−} cells. Validation by qRT-PCR revealed a significant decrease in basal expression of miR-196a in AhR{sup −/−} compared to AhR{sup +/+} cells. Exposure to AhR agonists benzo[a]pyrene (B[a]P) and FICZ as well as AhR antagonist CH-223191 decreased miR-196a expression in AhR{sup +/+} fibroblasts concomitant with decreased AhR protein levels. There was increased proliferation only in AhR{sup +/+} lung fibroblasts in response to serum, corresponding to a decrease in p27{sup KIP1} protein, a cyclin-dependent kinase inhibitor. Increasing the cellular levels of miR-196a had no effect on proliferation or expression of p27{sup KIP1} in AhR{sup −/−} fibroblasts but attenuated cigarette smoke-induced apoptosis. This study provides the first evidence that AhR expression is essential for the physiological regulation of cellular miRNA levels- including miR-196a. Future experiments designed to elucidate the functional relationship between the AhR and miR-196a may delineate additional novel ligand-independent roles for the AhR. - Highlights: • The AhR controls proliferation and apoptosis in lung cells. • The AhR regulates the

  11. In Vitro Transformation of Chlorinated Parabens by the Liver S9 Fraction: Kinetics, Metabolite Identification, and Aryl Hydrocarbon Receptor Agonist Activity.

    Science.gov (United States)

    Terasaki, Masanori; Wada, Takeshi; Nagashima, Satoshi; Makino, Masakazu; Yasukawa, Hiro

    2016-01-01

    We investigated the kinetics of in vitro transformation of a dichlorinated propyl paraben (2-propyl 3,5-dichloro-4-hydroxybenzoate; Cl2PP) by the rat liver S9 fraction and assessed the aryl hydrocarbon receptor (AhR) agonist activity of the metabolite products identified in HPLC and GC/MS analysis and by metabolite syntheses. The results indicated that the chlorination of Cl2PP reduced its degradation rate by approximately 40-fold. Two hydroxylated metabolite products showed AhR agonist activity of up to 39% of that of the parent Cl2PP when assessed in a yeast (YCM3) reporter gene assay. The determination of the metabolic properties of paraben bioaccumulation presented here provides further information on the value of risk assessments of chlorinated parabens as a means to ensure human health and environmental safety.

  12. Stress triggering of earthquakes and subsidence in the Louisiana coastal zone due to hydrocarbon production

    Science.gov (United States)

    Mallman, Ellen P.

    This thesis presents contributions towards better understanding of the interaction between earthquakes through elastic stress triggering and the role of hydrocarbon production on subsidence and land loss in southern Louisiana. The first issue addressed in this thesis is that of the role of static stress changes on earthquake triggering. The first study investigated whether observed changes in seismicity rate following the 1992 Landers, California and 1995 Kobe, Japan earthquakes are accurately predicted by elastic Coulomb stress transfer models. The analyses found that for all the tested DeltaCFS models wherever seismicity rate changes could be resolved the rate increased regardless of whether the DeltaCFS theoretically promoted or inhibited failure. The second study the common definition of a stress shadow was extended to independently test the stress shadow hypothesis using a global catalog of seismicity. The analyses indicated that while stress shadows are subtle, they are present in the global catalog. It also explains why "classical" stress shadows, similar to what was observed following the 1906 San Francisco earthquake are rarely observed for individual main shocks. The second issue addressed in this thesis is the role of hydrocarbon production on subsidence and land loss in the Louisiana Coastal Zone. The two studies in this thesis extend previous work by modeling the effect of oil and gas production in the region in two ways. First, multiple producing oil and gas fields and multiple epochs of leveling data are considered to provide constraints on predicted subsidence. Second, the role of compaction of the reservoir bounding shales on the regional subsidence signal is included. The results of the two studies on the role of hydrocarbon production on subsidence in the Louisiana Coastal Zone indicate that regional models of subsidence must include the effects of production-induced subsidence due to both sands and shales, but that this can not account for the

  13. The aryl hydrocarbon receptor-mediated and genotoxic effects of fractionated extract of standard reference diesel exhaust particle material in pulmonary, liver and prostate cells.

    Science.gov (United States)

    Pálková, Lenka; Vondráček, Jan; Trilecová, Lenka; Ciganek, Miroslav; Pěnčíková, Kateřina; Neča, Jiří; Milcová, Alena; Topinka, Jan; Machala, Miroslav

    2015-04-01

    Diesel exhaust particles (DEP) and the associated complex mixtures of organic pollutants, such as polycyclic aromatic hydrocarbons (PAHs), or their derivatives, have been suggested to exert deleterious effects on human health. We used a set of defined cellular models representing liver, lung and prostate tissues, in order to compare non-genotoxic and genotoxic effects of crude and fractionated extract of a standard reference DEP material - SRM 1650b. We focused on the aryl hydrocarbon receptor (AhR)-mediated activity, modulation of cell proliferation, formation of DNA adducts, oxidative DNA damage, and induction of DNA damage responses, including evaluation of apoptosis, and phosphorylation of p53 tumor suppressor and checkpoint kinases (Chk). Both PAHs and the polar aromatic compounds contributed to the AhR-mediated activity of DEP-associated organic pollutants. The principal identified AhR agonists included benzo[k]fluoranthene, indeno[1,2,3-c,d]pyrene, chrysene and several non-priority PAHs, including benzochrysenes and methylated PAHs. In contrast to PAHs, polar compounds contributed more significantly to overall formation of DNA adducts associated with phosphorylation of p53, Chk1 or Chk2, and partly with apoptosis. Therefore, more attention should be paid to identification of DEP-associated polar organic compounds, contributing to the AhR activation and cytotoxic/genotoxic effects of complex airborne mixtures of organic contaminants produced by diesel engines. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Effects of currently used pesticides and their mixtures on the function of thyroid hormone and aryl hydrocarbon receptor in cell culture

    Energy Technology Data Exchange (ETDEWEB)

    Ghisari, Mandana; Long, Manhai; Tabbo, Agnese; Bonefeld-Jørgensen, Eva Cecilie, E-mail: ebj@mil.au.dk

    2015-05-01

    Evidence suggest that exposure to pesticides can interfere with the endocrine system by multiple mechanisms. The endocrine disrupting potential of currently used pesticides in Denmark was analyzed as single compounds and in an equimolar mixture of 5 selected pesticides. The pesticides were previously analyzed for effects on the function of estrogen and androgen receptors, the aromatase enzyme and steroidogenesis in vitro. In this study, the effect on thyroid hormone (TH) function and aryl hydrocarbon receptor (AhR) transactivity was assessed using GH3 cell proliferation assay (T-screen) and AhR responsive luciferase reporter gene bioassay, respectively. Thirteen pesticides were analyzed as follows: 2-methyl-4-chlorophenoxyacetic acid, terbuthylazine, iodosulfuron-methyl-sodium, mesosulfuron-methyl, metsulfuron-methyl, chlormequat chloride, bitertanol, propiconazole, prothioconazole, mancozeb and its metabolite ethylene thiourea, cypermethrin, tau-fluvalinate, and malathion (currently banned in DK). In the T-screen, prothioconazole, malathion, tau-fluvalinate, cypermethrin, terbuthylazine and mancozeb significantly stimulated and bitertanol and propiconazole slightly reduced the GH3 cell proliferation. In the presence of triiodothyronine (T3), prothioconazole, tau-fluvalinate, propiconazole, cypermethrin and bitertanol significantly antagonized the T3-induced GH3 cell proliferation. Eleven of the tested pesticides agonized the AhR function, and bitertanol and prothioconazole inhibited the basal AhR activity. Bitertanol, propiconazole, prothioconazole and cypermethrin antagonized the TCDD-induced AhR transactivation at the highest tested concentration. The 5-component mixture had inducing effect but the combined effect could not be predicted due to the presence of bitertanol eliciting inhibitory effect. Upon removal of bitertanol from the mixture, the remaining four pesticides acted additively. In conclusion, our data suggest that pesticides currently used in Denmark

  15. Effects of the aryl hydrocarbon receptor agonist 3-methylcholanthrene on the 17β-estradiol regulated mRNA transcriptome of the rat uterus.

    Science.gov (United States)

    Helle, Janina; Keiler, Annekathrin M; Zierau, Oliver; Dörfelt, Peggy; Vollmer, Günter; Lehmann, Leane; Chittur, Sridar V; Tenniswood, Martin; Welsh, JoEllen; Kretzschmar, Georg

    2017-07-01

    Polycyclic aromatic hydrocarbons (PAHs) are products of incomplete combustion of organic compounds, abundant in exhaust fumes and cigarette smoke. They act by binding to the aryl hydrocarbon receptor (AHR) which induces expression of phase 1 and phase 2 enzymes in the liver. PAH induced AHR activation may also lead to adverse effects by modulating other pathways, for example estrogen receptor (ER) signaling in the female reproductive tract. We have investigated the effects of the PAH 3-methylcholanthrene (3-MC) on 17β-estradiol (E2) dependent signaling in the uterus of ovariectomized rats to characterize the cross talk between AHR and ER on an mRNA transcriptome wide scale. A standard three day uterotrophic assay was performed in young adult Lewis rats. Treatment induced effects were analyzed using histology, immunohistochemistry and gene expression analysis by microarray and qPCR. 3-MC shows broad E2 antagonistic effects on uterine mRNA transcription of the vast majority of E2 regulated genes, significantly altering prostaglandin biosynthesis, complement activation, coagulation pathways and other inflammatory response pathways. The regulation of ER expression in the uterus, but not the regulation of E2 metabolism in the liver, was identified as a potentially important factor in mediating this general antiestrogenic effect. The regulation of prostaglandin biosynthesis by E2 is important for inflammation-like events during pregnancy including the initiation of birth. Our results suggest that adverse effects of PAHs on prostaglandin related pathways are likely caused by the interference with E2 signaling, specifically by inhibiting the E2 mediated downregulation of PGF2α. Characterization of the generalized antagonistic effect of 3-MC on E2 dependent signaling in the rat uterus thus contributes to a better understanding of molecular mechanisms of the toxicity of PAHs in female reproductive organs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. TCF21 and the environmental sensor aryl-hydrocarbon receptor cooperate to activate a pro-inflammatory gene expression program in coronary artery smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Juyong Brian Kim

    2017-05-01

    Full Text Available Both environmental factors and genetic loci have been associated with coronary artery disease (CAD, however gene-gene and gene-environment interactions that might identify molecular mechanisms of risk are not easily studied by human genetic approaches. We have previously identified the transcription factor TCF21 as the causal CAD gene at 6q23.2 and characterized its downstream transcriptional network that is enriched for CAD GWAS genes. Here we investigate the hypothesis that TCF21 interacts with a downstream target gene, the aryl hydrocarbon receptor (AHR, a ligand-activated transcription factor that mediates the cellular response to environmental contaminants, including dioxin and polycyclic aromatic hydrocarbons (e.g., tobacco smoke. Perturbation of TCF21 expression in human coronary artery smooth muscle cells (HCASMC revealed that TCF21 promotes expression of AHR, its heterodimerization partner ARNT, and cooperates with these factors to upregulate a number of inflammatory downstream disease related genes including IL1A, MMP1, and CYP1A1. TCF21 was shown to bind in AHR, ARNT and downstream target gene loci, and co-localization was noted for AHR-ARNT and TCF21 binding sites genome-wide in regions of HCASMC open chromatin. These regions of co-localization were found to be enriched for GWAS signals associated with cardio-metabolic as well as chronic inflammatory disease phenotypes. Finally, we show that similar to TCF21, AHR gene expression is increased in atherosclerotic lesions in mice in vivo using laser capture microdissection, and AHR protein is localized in human carotid atherosclerotic lesions where it is associated with protein kinases with a critical role in innate immune response. These data suggest that TCF21 can cooperate with AHR to activate an inflammatory gene expression program that is exacerbated by environmental stimuli, and may contribute to the overall risk for CAD.

  17. The Role of Aryl Hydrocarbon Receptor and Crosstalk with Estrogen Receptor in Response of Breast Cancer Cells to the Novel Antitumor Agents Benzothiazoles and Aminoflavone

    Directory of Open Access Journals (Sweden)

    Mariana A. Callero

    2011-01-01

    Full Text Available Many estrogen-receptor- (ER- expressing breast cancers become refractory to ER-based therapies. New antitumor drugs like aminoflavone (AF and benzothiazoles (Bzs have been developed and have exquisite antitumor activity in ER+MCF-7 and T47D cells and in a MCF-7 nude mouse model. ER(− breast cancer cells like MDA-MB-231 are less susceptible. We previously found in MCF-7 cells that these drugs activate the aryl hydrocarbon receptor (AhR via translocation to the nucleus, induction of AhR-specific DNA binding activity, and expression of CYP1A1, whose transcription is controlled by the AhR-ARNT transcription factor. CYP1A1 metabolizes AF and Bz to a species which directly or after further metabolism damages DNA. In contrast an AhR-deficient variant of MCF-7 or cells with predominantly nuclear AhR expression, such as MDA-MB 231, are resistant. Thus, these drugs, unlike other neoplastic agents, require AhR-mediated signaling to cause DNA damage. This is a new treatment strategy for breast cancers with intact AhR signaling.

  18. Xenoestrogens down-regulate aryl-hydrocarbon receptor nuclear translocator 2 mRNA expression in human breast cancer cells via an estrogen receptor alpha-dependent mechanism.

    Science.gov (United States)

    Qin, Xian-Yang; Zaha, Hiroko; Nagano, Reiko; Yoshinaga, Jun; Yonemoto, Junzo; Sone, Hideko

    2011-10-10

    Environmental chemicals with estrogenic activity, known as xenoestrogens, may cause impaired reproductive development and endocrine-related cancers in humans by disrupting endocrine functions. Aryl-hydrocarbon receptor nuclear translocator 2 (ARNT2) is believed to play important roles in a variety of physiological processes, including estrogen signaling pathways, that may be involved in the pathogenesis and therapeutic responses of endocrine-related cancers. However, much of the underlying mechanism remains unknown. In this study, we investigated whether ARNT2 expression is regulated by a range of representative xenoestrogens in human cancer cell lines. Bisphenol A (BPA), benzyl butyl phthalate (BBP), and 1,1,1-trichloro-2,2-bis(2-chlorophenyl-4-chlorophenyl)ethane (o,p'-DDT) were found to be estrogenic toward BG1Luc4E2 cells by an E-CALUX bioassay. ARNT2 expression was downregulated by BPA, BBP, and o,p'-DDT in a dose-dependent manner in estrogen receptor 1 (ESR1)-positive MCF-7 and BG1Luc4E2 cells, but not in estrogen receptor-negative LNCaP cells. The reduction in ARNT2 expression in cells treated with the xenoestrogens was fully recovered by the addition of a specific ESR1 antagonist, MPP. In conclusion, we have shown for the first time that ARNT2 expression is modulated by xenoestrogens by an ESR1-dependent mechanism in MCF-7 breast cancer cells. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  19. Inhibition of aryl hydrocarbon receptor-dependent transcription by resveratrol or kaempferol is independent of estrogen receptor α expression in human breast cancer cells

    Science.gov (United States)

    MacPherson, Laura; Matthews, Jason

    2016-01-01

    Resveratrol and kaempferol are natural chemopreventative agents that are also aryl hydrocarbon receptor (AHR) antagonists and estrogen receptor (ER) agonists. In this study we evaluated the role of ERα in resveratrol- and kaempferol-mediated inhibition of AHR-dependent transcription. Kaempferol or resveratrol inhibited dioxin-induced cytochrome P450 1A1 (CYP1A1) and CYP1B1 expression levels and recruitment of AHR, ERα and co-activators to CYP1A1 and CYP1B1. Both phytochemicals induced the expression and recruitment of ERα to gene amplified in breast cancer 1 (GREB1). RNAi-mediated knockdown of ERα in T-47D cells did not affect the inhibitory action of either phytochemical on AHR activity. Both compounds also inhibited AHR-dependent transcription in ERα-negative MDA-MB-231 and BT-549 breast cancer cells. These data show that ERα does not contribute to the AHR-inhibitory activities of resveratrol and kaempferol. PMID:20846786

  20. Characterisation of chlorinated, brominated and mixed halogenated dioxins, furans and biphenyls as potent and as partial agonists of the Aryl hydrocarbon receptor.

    Science.gov (United States)

    Wall, Richard J; Fernandes, Alwyn; Rose, Martin; Bell, David R; Mellor, Ian R

    2015-03-01

    The Aryl hydrocarbon receptor (AhR) binds a variety of chlorinated and brominated dioxins, furans and biphenyls. Mixed halogenated variants have been recently identified in food at significant levels but full characterisation requires potency data in order to gauge their impact on risk assessment. Rat H4IIE and human MCF-7 cells were treated with various mixed halogenated ligands. Antagonist properties were measured by treating cells with various concentrations of TCDD in the presence of EC25 of the putative antagonist. Measurement of CYP1A1 RNA was used to quantify the potency of agonism and antagonism. The PXDDs were found to be slightly less potent than the corresponding fully chlorinated congeners with the exception of 2-B,3,7,8-TriCDD which was 2-fold more potent than TCDD. PXDFs and non-ortho-PXBs were found to be more potent than their chlorinated congeners whilst several mono-ortho-substituted PXBs were shown to have partial agonistic properties. REPs were produced for a range of mixed halogenated AhR-activating ligands providing a more accurate estimation of potency for risk assessment. Several environmentally abundant biphenyls were shown to be antagonists and reduce the ability of TCDD to induce CYP1A1. The demonstration of antagonism for AhR ligands represents a challenge for existing REP risk assessment schemes for AhR ligands. Copyright © 2014. Published by Elsevier Ltd.

  1. Berberine Activates Aryl Hydrocarbon Receptor but Suppresses CYP1A1 Induction through miR-21-3p Stimulation in MCF-7 Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Sheng-Nan Lo

    2017-10-01

    Full Text Available Berberine and the methylenedioxy ring-opening derivatives palmatine and jatrorrhizine are active ingredients in immunomodulatory plants, such as goldenseal. This study aimed to illustrate the effects of protoberberines on aryl hydrocarbon receptor (AhR activation and cytochrome P450 (CYP 1 in the estrogen receptor (ERα(+ MCF-7 breast cancer cells. Among protoberberines at non-cytotoxic concentrations (≤10 μM, berberine had the most potent and statistically significant effects on AhR activation and CYP1A1/1A2/1B1 mRNA induction. The 24-h exposure to 10 μM berberine did not change CYP1A1 mRNA stability, protein level and function. Berberine significantly increased micro RNA (miR-21-3p by 36% and the transfection of an inhibitor of miR-21-3p restored the induction of CYP1A1 protein with a 50% increase. These findings demonstrate that the ring opening of the methylenedioxyl moiety in berberine decreased AhR activation in MCF-7 cells. While CYP1A1 mRNA was elevated, berberine-induced miR-21-3p suppressed the increase of functional CYP1A1 protein expression.

  2. Hippocampal expression of aryl hydrocarbon receptor nuclear translocator 2 and neuronal PAS domain protein 4 in a rat model of depression.

    Science.gov (United States)

    Zhang, Zhaohui; Fei, Pengge; Mu, Junlin; Li, Wenqiang; Song, Jinggui

    2014-02-01

    The transcription factors aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) and neuronal PAS domain protein 4 (NPAS4) may influence emotion and cognitive function by regulating brain-derived neurotrophic factor expression in the hippocampus. We estimated hippocampal ARNT2 and NPAS4 expression in chronic unexpected mild stress (CUMS) rat model. The possible association was investigated between expression of these transcription factors and depressive behaviors. Behavioral tests were conducted before, during, and after 28 days of group housing or isolation plus CUMS. The sucrose solution consumption test was used to assess changes in interest and pleasure-seeking, and the open field test (OFT) was conducted to measure spontaneous activity and exploratory behavior. Expression levels of ARNT2 and NPAS4 were estimated by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Compared to controls, rats subjected to isolation plus CUMS exhibited significantly reduced weight gain (t = 9.317, P = 0.000), sucrose consumption (t = 3.756, P = 0.003), horizontal ambulation (t = 2.362, P = 0.041), and number of rearings (vertical motion) (t = 2.268, P = 0.040). Relative hippocampal NPAS4 expression was significantly lower in depression model rats compared to controls (t = 2.995, P = 0.010) but there was no significant difference in hippocampal ARNT2 expression between groups (t = 0.091, P = 0.929). The relationship between the CUMS model of depression and NPAS4 expression requires further exploration.

  3. Phytomonitoring and phytoremediation of agrochemicals and related compounds based on recombinant cytochrome P450s and aryl hydrocarbon receptors (AhRs).

    Science.gov (United States)

    Shimazu, Sayuri; Inui, Hideyuki; Ohkawa, Hideo

    2011-04-13

    Molecular mechanisms of metabolism and modes of actions of agrochemicals and related compounds are important for understanding selective toxicity, biodegradability, and monitoring of biological effects on nontarget organisms. It is well-known that in mammals, cytochrome P450 (P450 or CYP) monooxygenases metabolize lipophilic foreign compounds. These P450 species are inducible, and both CYP1A1 and CYP1A2 are induced by aryl hydrocarbon receptor (AhR) combined with a ligand. Gene engineering of P450 and NADPH cytochrome P450 oxidoreductase (P450 reductase) was established for bioconversion. Also, gene modification of AhRs was developed for recombinant AhR-mediated β-glucronidase (GUS) reporter assay of AhR ligands. Recombinant P450 genes were transformed into plants for phytoremediation, and recombinant AhR-mediated GUS reporter gene expression systems were each transformed into plants for phytomonitoring. Transgenic rice plants carrying CYP2B6 metabolized the herbicide metolachlor and remarkably reduced the residues in the plants and soils under paddy field conditions. Transgenic Arabidopsis plants carrying recombinant guinea pig (g) AhR-mediated GUS reporter genes detected PCB126 at the level of 10 ng/g soils in the presence of biosurfactants MEL-B. Both phytomonitoring and phytoremediation plants were each evaluated from the standpoint of practical uses.

  4. Genetic variability of aryl hydrocarbon receptor (AhR)-mediated regulation of the human UDP glucuronosyltransferase (UGT) 1A4 gene

    International Nuclear Information System (INIS)

    Erichsen, Thomas J.; Ehmer, Ursula; Kalthoff, Sandra; Lankisch, Tim O.; Mueller, Tordis M.; Munzel, Peter A.; Manns, Michael P.; Strassburg, Christian P.

    2008-01-01

    UDP glucuronosyltransferases (UGTs) play an important role for drug detoxification and toxicity. UGT function is genetically modulated by single nucleotide polymorphisms (SNPs) which lead to the expression of functionally altered protein, or altered expression levels. UGT1A4 activity includes anticonvulsants, antidepressants and environmental mutagens. In this study the induction of the human UGT1A4 gene and a potential influence of genetic variation in its promoter region were analyzed. SNPs at bp - 219 and - 163 occurred in 9% among 109 blood donors reducing UGT1A4 transcription by 40%. UGT1A4 transcription was dioxin inducible. Reporter gene experiments identified 2 xenobiotic response elements (XRE), which were functionally confirmed by mutagenesis analyses, and binding was demonstrated by electromobility shift assays. Constitutive human UGT1A4 gene expression and induction was aryl hydrocarbon receptor (AhR)-dependent, and reduced in the presence of SNPs at bp - 219 and - 163. AhR-mediated regulation of the human UGT1A4 gene by two XRE and a modulation by naturally occurring genetic variability by SNPs is demonstrated, which indicates gene-environment interaction with potential relevance for drug metabolism

  5. Docking-based three-dimensional quantitative structure-activity relationship (3D-QSAR) predicts binding affinities to aryl hydrocarbon receptor for polychlorinated dibenzodioxins, dibenzofurans, and biphenyls.

    Science.gov (United States)

    Yuan, Jintao; Pu, Yuepu; Yin, Lihong

    2013-07-01

    Polychlorinated dibenzodioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) cause toxic effects after binding to an intracellular cytosolic receptor called the aryl hydrocarbon receptor (AhR). Thymic atrophy, weight loss, immunotoxicity, acute lethality, and induction of cytochrome P4501A1 have all been correlated with the binding affinity to AhR. To study the key molecular features for determining binding affinity to AhR, a homology model of AhR ligand-binding domains was developed, a molecular docking approach was employed to obtain docking-based conformations of all molecules in the whole set, and 3-dimensional quantitative structure-activity relationship (3D-QSAR) methodology, namely, comparative molecular field analysis (CoMFA), was applied. A partial least square analysis was performed, and QSAR models were generated for a training set of 59 compounds. The generated QSAR model showed good internal and external statistical reliability, and in a comparison with other reported CoMFA models using different alignment methods, the docking-based CoMFA model showed some advantages. Copyright © 2013 SETAC.

  6. A Structural Switch between Agonist and Antagonist Bound Conformations for a Ligand-Optimized Model of the Human Aryl Hydrocarbon Receptor Ligand Binding Domain

    Directory of Open Access Journals (Sweden)

    Arden Perkins

    2014-10-01

    Full Text Available The aryl hydrocarbon receptor (AHR is a ligand-activated transcription factor that regulates the expression of a diverse group of genes. Exogenous AHR ligands include the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, which is a potent agonist, and the synthetic AHR antagonist N-2-(1H-indol-3ylethyl-9-isopropyl-2- (5-methylpyridin-3-yl-9H-purin-6-amine (GNF351. As no experimentally determined structure of the ligand binding domain exists, homology models have been utilized for virtual ligand screening (VLS to search for novel ligands. Here, we have developed an “agonist-optimized” homology model of the human AHR ligand binding domain, and this model aided in the discovery of two human AHR agonists by VLS. In addition, we performed molecular dynamics simulations of an agonist TCDD-bound and antagonist GNF351-bound version of this model in order to gain insights into the mechanics of the AHR ligand-binding pocket. These simulations identified residues 307–329 as a flexible segment of the AHR ligand pocket that adopts discrete conformations upon agonist or antagonist binding. This flexible segment of the AHR may act as a structural switch that determines the agonist or antagonist activity of a given AHR ligand.

  7. Insulin/insulin like growth factors in cancer: new roles for the aryl hydrocarbon receptor, tumor resistance mechanisms and new blocking strategies

    Directory of Open Access Journals (Sweden)

    Travis B Salisbury

    2015-02-01

    Full Text Available The insulin-like growth factor 1 receptor (IGF1R and the insulin receptor (IR are receptor tyrosine kinases (RTKs that are expressed in cancer cells. The results of different studies indicate that tumor proliferation and survival is dependent on the IGF1R and IR, and that their inhibition leads to reductions in proliferation and increases in cell death. Molecular targeting therapies that have been used in solid tumors include: anti-IGF1R antibodies, anti-IGF1/IGF2 antibodies and small molecule inhibitors that suppress IGF1R and IR kinase activity. New advances in the molecular basis of anti-IGF1R blocking antibodies reveal they are biased agonists and promote the binding of IGF1 to integrin β3 receptors in some cancer cells. Our recent reports indicate that pharmacological aryl hydrocarbon receptor (AHR ligands inhibit breast cancer cell responses to IGFs, suggesting that targeting AHR may have benefit in cancers whose proliferation and survival are dependent on insulin/IGF signaling. Novel aspects of IGF1R/IR in cancer, such as biased agonism, integrin β3 signaling, AHR and new therapeutic targeting strategies will be discussed.

  8. TRIGGER

    CERN Multimedia

    Wesley Smith

    Level-1 Trigger Hardware and Software The hardware of the trigger components has been mostly finished. The ECAL Endcap Trigger Concentrator Cards (TCC) are in production while Barrel TCC firmware has been upgraded, and the Trigger Primitives can now be stored by the Data Concentrator Card for readout by the DAQ. The Regional Calorimeter Trigger (RCT) system is complete, and the timing is being finalized. All 502 HCAL trigger links to RCT run without error. The HCAL muon trigger timing has been equalized with DT, RPC, CSC and ECAL. The hardware and firmware for the Global Calorimeter Trigger (GCT) jet triggers are being commissioned and data from these triggers is available for readout. The GCT energy sums from rings of trigger towers around the beam pipe beam have been changed to include two rings from both sides. The firmware for Drift Tube Track Finder, Barrel Sorter and Wedge Sorter has been upgraded, and the synchronization of the DT trigger is satisfactory. The CSC local trigger has operated flawlessly u...

  9. TRIGGER

    CERN Multimedia

    Roberta Arcidiacono

    2013-01-01

    Trigger Studies Group (TSG) The Trigger Studies Group has just concluded its third 2013 workshop, where all POGs presented the improvements to the physics object reconstruction, and all PAGs have shown their plans for Trigger development aimed at the 2015 High Level Trigger (HLT) menu. The Strategy for Trigger Evolution And Monitoring (STEAM) group is responsible for Trigger menu development, path timing, Trigger performance studies coordination, HLT offline DQM as well as HLT release, menu and conditions validation – this last task in collaboration with PdmV (Physics Data and Monte Carlo Validation group). In the last months the group has delivered several HLT rate estimates and comparisons, using the available data and Monte Carlo samples. The studies were presented at the Trigger workshops in September and December, and STEAM has contacted POGs and PAGs to understand the origin of the discrepancies observed between 8 TeV data and Monte Carlo simulations. The most recent results show what the...

  10. 2,3,7,8-Tetrachlorodibenzo-p-dioxin treatment alters eicosanoid levels in several organs of the mouse in an aryl hydrocarbon receptor-dependent fashion.

    Science.gov (United States)

    Bui, Peter; Solaimani, Parrisa; Wu, Xiaomeng; Hankinson, Oliver

    2012-03-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) adversely affects many mammalian organs and tissues. These effects are mediated by the aryl hydrocarbon receptor (AHR). CYP1A1, CYP1A2 and CYP1B1 are upregulated by the liganded AHR. These (and other) cytochromes P450 can metabolize arachidonic acid into a variety of bioactive eicosanoids. Towards investigating a potential role of eicosanoids in TCDD toxicity, arachidonic acid, two other unsaturated long-chain fatty acids, and up to twenty-five eicosanoids were measured in five organs/tissues of male and female wild-type and Ahr null mice treated or untreated with TCDD. TCDD generally increased the levels of the four dihydroxyeicosatrienoic acids (DHETs) and (where measured) 5,6-epoxyeicosatrienoic acid and 18-, 19- and 20-hydroxyeicosatrienoic acids (HETEs) in the serum, liver, spleen and lungs, but not the heart, of both sexes, and increased the levels in the serum, liver and spleen of several metabolites that are usually considered products of lipoxygenase activity, but which may also be generated by cytochromes P450. TCDD also increased the levels of the esterified forms of these eicosanoids in the liver in parallel with the corresponding free forms. The levels of prostanoids were generally not affected by TCDD. The above changes did not occur in Ahr null mice, and are therefore mediated by the AHR. TCDD increased the mRNA levels of Cyp1a1, Cyp1a2, Cyp1b1 and the Pla2g12a form of phospholipase A(2) to varying degrees in the different organs, and these increases correlated with some but not all the changes in eicosanoids levels in the organs, suggesting that other enzymes may also be involved. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Aryl hydrocarbon receptor suppresses the osteogenesis of mesenchymal stem cells in collagen-induced arthritic mice through the inhibition of β-catenin

    Energy Technology Data Exchange (ETDEWEB)

    Tong, Yulong [Department of Immunology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men, Beijing 100069 (China); Niu, Menglin [Department of Immunology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men, Beijing 100069 (China); Department of Blood Transfusion, Peking University Cancer Hospital & Institute, No. 52 Fucheng Rd., Beijing 100142 (China); Du, Yuxuan; Mei, Wentong; Cao, Wei; Dou, Yunpeng [Department of Immunology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men, Beijing 100069 (China); Yu, Haitao [Department of Clinical Laboratory, The First Hospital of Lanzhou University, Lanzhou, Gansu Province 730000 (China); Du, Xiaonan [Department of Immunology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men, Beijing 100069 (China); Yuan, Huihui, E-mail: huihui_yuan@163.com [Department of Immunology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men, Beijing 100069 (China); Zhao, Wenming, E-mail: zhao-wenming@163.com [Department of Immunology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men, Beijing 100069 (China)

    2017-01-15

    The contributions of aryl hydrocarbon receptor (Ahr) to the pathogenesis of rheumatoid arthritis (RA), particularly bone loss, have not been clearly explored. The imbalance between osteoblasts and osteoclasts is a major reason for bone loss. The dysfunction of osteoblasts, which are derived from mesenchymal stem cells (MSCs), induced bone erosion occurs earlier and is characterized as more insidious. Here, we showed that the nuclear expression and translocation of Ahr were both significantly increased in MSCs from collagen-induced arthritis (CIA) mice. The enhanced Ahr suppressed the mRNA levels of osteoblastic markers including Alkaline phosphatase (Alp) and Runt-related transcription factor 2 (Runx2) in the differentiation of MSCs to osteoblasts in CIA. The 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated activation of Ahr dose-dependently suppressed the expression of osteoblastic markers. In addition, the expression of β-catenin was reduced in CIA MSCs compared with control, and the TCDD-mediated activation of the Ahr significantly inhibited β-catenin expression. The Wnt3a-induced the activation of Wnt/β-catenin pathway partly rescued the osteogenesis decline induced by TCDD. Taken together, these results indicate that activated Ahr plays a negative role in CIA MSCs osteogenesis, possibly by suppressing the expression of β-catenin. - Highlights: • The Ahr pathway displays an activated profile in CIA MSCs. • The activation of Ahr suppresses osteogenesis in CIA MSCs. • TCDD suppresses osteogenesis in a dose-dependent manner. • The activation of Ahr inhibits β-catenin expression to exacerbate bone erosion.

  12. Aryl hydrocarbon receptor regulates cell cycle progression in human breast cancer cells via a functional interaction with cyclin-dependent kinase 4.

    Science.gov (United States)

    Barhoover, Melissa A; Hall, Julie M; Greenlee, William F; Thomas, Russell S

    2010-02-01

    The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor with constitutive activities and those induced by xenobiotic ligands, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). One unexplained cellular role for the AHR is its ability to promote cell cycle progression in the absence of exogenous ligands, whereas treatment with exogenous ligands induces cell cycle arrest. Within the cell cycle, progression from G(1) to S phase is controlled by sequential phosphorylation of the retinoblastoma protein (RB1) by cyclin D-cyclin-dependent kinase (CDK) 4/6 complexes. In this study, the functional interactions between the AHR, CDK4, and cyclin D1 (CCND1) were investigated as a potential mechanism for the cell cycle regulation by the AHR. Time course cell cycle and molecular experiments were performed in human breast cancer cells. The results demonstrated that the AHR and CDK4 interact within the cell cycle, and the interaction was disrupted upon TCDD treatment. The disruption was temporally correlated with G(1) cell cycle arrest and decreased phosphorylation of RB1. Biochemical reconstitution assays using in vitro-translated protein recapitulated the AHR and CDK4 interaction and showed that CCND1 was also part of the complex. In vitro assays for CDK4 kinase activity demonstrated that RB1 phosphorylation by the AHR/CDK4/CCND1 complex was reduced in the presence of TCDD. The results suggest that the AHR interacts in a complex with CDK4 and CCND1 in the absence of exogenous ligands to facilitate cell cycle progression. This interaction is disrupted by exogenous ligands, such as TCDD, to induce G(1) cell cycle arrest.

  13. Aminoflavone, a ligand of the Aryl Hydrocarbon Receptor (AhR), inhibits HIF-1α expression in an AhR-independent fashion

    Science.gov (United States)

    Terzuoli, Erika; Puppo, Maura; Rapisarda, Annamaria; Uranchimeg, Badarch; Cao, Liang; Burger, Angelika M.; Ziche, Marina; Melillo, Giovanni

    2010-01-01

    Aminoflavone (AF), the active component of a novel anticancer agent (AFP464) in phase I clinical trials, is a ligand of the aryl hydrocarbon receptor (AhR). AhR dimerizes with HIF-1β/ARNT, which is shared with HIF-1α, a transcription factor critical for the response of cells to oxygen deprivation. To address whether pharmacological activation of the AhR pathway might be a potential mechanism for inhibition of HIF-1, we tested the effects of AF on HIF-1 expression. AF inhibited HIF-1α transcriptional activity and protein accumulation in MCF-7 cells. However, inhibition of HIF-1α by AF was independent from a functional AhR pathway. Indeed, AF inhibited HIF-1α expression in AhR100 cells, in which the AhR pathway is functionally impaired, yet did not induce cytotoxicity, providing evidence that these effects are mediated by distinct signaling pathways. Moreover, AF was inactive in MDA-MB-231 cells, yet inhibited HIF-1α in MDA-MB-231 cells transfected with the SULT1A1 gene. AF inhibited HIF-1α mRNA expression by approximately 50%. Notably, actinomycin-D completely abrogated the ability of AF to down-regulate HIF-1α mRNA, indicating that active transcription was required for the inhibition of HIF-1α expression. Finally, AF inhibited HIF-1α protein accumulation and the expression of HIF-1-target genes in MCF-7 xenografts. These results demonstrate that AF inhibits HIF-1α in an AhR-independent fashion and they unveil additional activities of AF that may be relevant for its further clinical development. PMID:20736373

  14. The Mitochondria-Targeted Antioxidant SkQ1 Downregulates Aryl Hydrocarbon Receptor-Dependent Genes in the Retina of OXYS Rats with AMD-Like Retinopathy

    Directory of Open Access Journals (Sweden)

    M. L. Perepechaeva

    2014-01-01

    Full Text Available The mitochondria-targeted antioxidant SkQ1 is a novel drug thought to retard development of age-related diseases. It has been shown that SkQ1 reduces clinical signs of retinopathy in senescence-accelerated OXYS rats, which are a known animal model of human age-related macular degeneration (AMD. The aim of this work was to test whether SkQ1 affects transcriptional activity of AhR (aryl hydrocarbon receptor and Nrf2 (nuclear factor erythroid 2-related factor 2, which are considered as AMD-associated genes in the retina of OXYS and Wistar rats. Our results showed that only AhR and AhR-dependent genes were sensitive to SkQ1. Dietary supplementation with SkQ1 decreased the AhR mRNA level in both OXYS and Wistar rats. At baseline, the retinal Cyp1a1 mRNA level was lower in OXYS rats. SkQ1 supplementation decreased the Cyp1a1 mRNA level in Wistar rats, but this level remained unchanged in OXYS rats. Baseline Cyp1a2 and Cyp1b1 mRNA expression was stronger in OXYS than in Wistar rats. In the OXYS strain, Cyp1a2 and Cyp1b1 mRNA levels decreased as a result of SkQ1 supplementation. These data suggest that the Cyp1a2 and Cyp1b1 enzymes are involved in the pathogenesis of AMD-like retinopathy of OXYS rats and are possible therapeutic targets of SkQ1.

  15. Epigenetic Determinants of CYP1A1 Induction by the Aryl Hydrocarbon Receptor Agonist 3,3',4,4',5-Pentachlorobiphenyl (PCB 126

    Directory of Open Access Journals (Sweden)

    Sabine U. Vorrink

    2014-08-01

    Full Text Available Many enzymes involved in xenobiotic metabolism, including cytochrome P450 (CYP 1A1, are regulated by the aryl hydrocarbon receptor (AhR. 3,3',4,4',5-Penta chlorobiphenyl (PCB 126 is a potent ligand for AhR and can thus induce the expression of CYP1A1. Interestingly, we observed that human carcinoma cell lines derived from different types of epithelial cells displayed divergent degrees of CYP1A1 induction after exposure to PCB 126. Since epigenetic mechanisms are known to be involved in cell type-specific gene expression, we sought to assess the epigenetic determinants of CYP1A1 induction in these carcinoma cell lines. In contrast to HepG2 hepatocarcinoma cells, HeLa cervical carcinoma cells showed significantly lower levels of CYP1A1 mRNA expression following PCB 126 exposure. Our results show that the two cell lines maintained differences in the chromatin architecture along the CYP1A1 promoter region. Furthermore, treatment with the epigenetic modifiers, trichostatin A (TSA and 5-aza-2'-deoxycytidine (5-Aza-dC, significantly increased the expression of CYP1A1 after PCB 126 treatment in HeLa cells. However, we did not observe apparent differences in methylation levels or specific location of CpG DNA methylation between the two cell lines in the analyzed CYP1A1 promoter region. Taken together, our findings suggest that the differences in CYP1A1 expression between HepG2 and HeLa cells are due to differences in the chromatin architecture of the CYP1A1 promoter and thus establish a role of epigenetic regulation in cell-specific CYP1A1 expression.

  16. Modulation of aryl hydrocarbon receptor target genes in circulating lymphocytes from dairy cows bred in a dioxin-like PCB contaminated area

    Energy Technology Data Exchange (ETDEWEB)

    Girolami, Flavia, E-mail: flavia.girolami@unito.it [Department of Animal Pathology, University of Turin, Via Leonardo da Vinci 44, 10095 Grugliasco (Italy); Spalenza, Veronica, E-mail: veronica.spalenza@unito.it [Department of Animal Production, Epidemiology and Ecology, University of Turin, Via Leonardo da Vinci 44, 10095 Grugliasco (Italy); Carletti, Monica, E-mail: monica.carletti@unito.it [Department of Animal Pathology, University of Turin, Via Leonardo da Vinci 44, 10095 Grugliasco (Italy); Sacchi, Paola, E-mail: paola.sacchi@unito.it [Department of Animal Production, Epidemiology and Ecology, University of Turin, Via Leonardo da Vinci 44, 10095 Grugliasco (Italy); Rasero, Roberto, E-mail: roberto.rasero@unito.it [Department of Animal Production, Epidemiology and Ecology, University of Turin, Via Leonardo da Vinci 44, 10095 Grugliasco (Italy); Nebbia, Carlo, E-mail: carlo.nebbia@unito.it [Department of Animal Pathology, University of Turin, Via Leonardo da Vinci 44, 10095 Grugliasco (Italy)

    2013-04-15

    Animal productions (i.e. fish, eggs, milk and dairy products) represent the major source of exposure to dioxins, furans, and dioxin-like (DL) polychlorobiphenyls for humans. The negative effects of these highly toxic and persistent pollutants are mediated by the activation of the aryl hydrocarbon receptor (AHR) that elicits the transcriptional induction of several genes, including those involved in xenobiotic metabolism. Previously we demonstrated the presence and functioning of the AHR signaling pathway in primary cultures of bovine blood lymphocytes. The aim of the present study was to investigate by real time PCR the expression and the inducibility of selected target genes (i.e. AHR, AHR nuclear translocator (ARNT), AHR repressor, CYP1A1 and CYP1B1) in uncultured cells from dairy cows naturally exposed to DL-compounds. The study was carried out on two groups of animals bred in a highly polluted area and characterized by a different degree of contamination, as assessed by bulk milk TEQ values, and a control group reared in an industry free area. Bovine lymphocytes expressed only AHR, ARNT and CYP1B1 genes to a detectable level; moreover, only CYP1B1 expression appeared to be correlated to TEQ values, being higher in the most contaminated group, and decreasing along with animal decontamination. Finally, lymphocytes from exposed cows displayed a lower inducibility of both CYP1A1 and CYP1B1 after the in vitro treatment with a specific AHR ligand. In conclusion, our results indicate that DL-compound contaminated cows may display significant changes in AHR-target gene expression of circulating lymphocytes. - Highlights: ► The expression of AHR-target genes in blood bovine lymphocytes was evaluated. ► The lymphocyte CYP1B1 expression appears to be related to bulk milk TEQ values. ► Blood lymphocytes from dairy cows might represent a matrix for dioxin biomonitoring.

  17. Modulation of aryl hydrocarbon receptor target genes in circulating lymphocytes from dairy cows bred in a dioxin-like PCB contaminated area

    International Nuclear Information System (INIS)

    Girolami, Flavia; Spalenza, Veronica; Carletti, Monica; Sacchi, Paola; Rasero, Roberto; Nebbia, Carlo

    2013-01-01

    Animal productions (i.e. fish, eggs, milk and dairy products) represent the major source of exposure to dioxins, furans, and dioxin-like (DL) polychlorobiphenyls for humans. The negative effects of these highly toxic and persistent pollutants are mediated by the activation of the aryl hydrocarbon receptor (AHR) that elicits the transcriptional induction of several genes, including those involved in xenobiotic metabolism. Previously we demonstrated the presence and functioning of the AHR signaling pathway in primary cultures of bovine blood lymphocytes. The aim of the present study was to investigate by real time PCR the expression and the inducibility of selected target genes (i.e. AHR, AHR nuclear translocator (ARNT), AHR repressor, CYP1A1 and CYP1B1) in uncultured cells from dairy cows naturally exposed to DL-compounds. The study was carried out on two groups of animals bred in a highly polluted area and characterized by a different degree of contamination, as assessed by bulk milk TEQ values, and a control group reared in an industry free area. Bovine lymphocytes expressed only AHR, ARNT and CYP1B1 genes to a detectable level; moreover, only CYP1B1 expression appeared to be correlated to TEQ values, being higher in the most contaminated group, and decreasing along with animal decontamination. Finally, lymphocytes from exposed cows displayed a lower inducibility of both CYP1A1 and CYP1B1 after the in vitro treatment with a specific AHR ligand. In conclusion, our results indicate that DL-compound contaminated cows may display significant changes in AHR-target gene expression of circulating lymphocytes. - Highlights: ► The expression of AHR-target genes in blood bovine lymphocytes was evaluated. ► The lymphocyte CYP1B1 expression appears to be related to bulk milk TEQ values. ► Blood lymphocytes from dairy cows might represent a matrix for dioxin biomonitoring

  18. Liver Tumor Promotion by 2,3,7,8-Tetrachlorodibenzo-p-dioxin Is Dependent on the Aryl Hydrocarbon Receptor and TNF/IL-1 Receptors

    Science.gov (United States)

    Kennedy, Gregory D.; Nukaya, Manabu; Moran, Susan M.; Glover, Edward; Weinberg, Samuel; Balbo, Silvia; Hecht, Stephen S.; Pitot, Henry C.; Drinkwater, Norman R.; Bradfield, Christopher A.

    2014-01-01

    We set out to better understand the signal transduction pathways that mediate liver tumor promotion by 2,3,7,8-tetrachlorodibenzo-p-dioxn (“dioxin”). To this end, we first employed congenic mice homozygous for either the Ahrb1 or Ahrd alleles (encoding an aryl hydrocarbon receptor (AHR) with high or low binding affinity for dioxin, respectively) and demonstrated that hepatocellular tumor promotion in response to dioxin segregated with the Ahr locus. Once we had genetic evidence for the importance of AHR signaling, we then asked if tumor promotion by dioxin was influenced by “interleukin-1 (IL-1)-like” inflammatory cytokines. The importance of this question arose from our earlier observation that aspects of the acute hepatocellular toxicity of dioxin are dependent upon IL1-like cytokine signaling. To address this issue, we employed a triple knock-out (TKO) mouse model with null alleles at the loci encoding the three relevant receptors for tumor necrosis factors α and β and IL-1α and IL-1β (i.e., null alleles at the Tnfrsf1a, Tnfrsf1b, and Il-1r1 loci). The observation that TKO mice were resistant to the tumor promoting effects of dioxin in liver suggests that inflammatory cytokines play an important step in dioxin mediated liver tumor promotion in the mouse. Collectively, these data support the idea that the mechanism of dioxin acute hepatotoxicity and its activity as a promoter in a mouse two stage liver cancer model may be similar, i.e., tumor promotion by dioxin, like acute hepatotoxicity, are mediated by the linked action of two receptor systems, the AHR and the receptors for the “IL-1-like” cytokines. PMID:24718703

  19. Perturbation effect of reduced graphene oxide quantum dots (rGOQDs) on aryl hydrocarbon receptor (AhR) pathway in zebrafish.

    Science.gov (United States)

    Zhang, Jing-Hui; Sun, Tai; Niu, Aping; Tang, Yu-Mei; Deng, Shun; Luo, Wei; Xu, Qun; Wei, Dapeng; Pei, De-Sheng

    2017-07-01

    Graphene quantum dots (GQDs) has been widely used in enormous fields, however, the inherent molecular mechanism of GQDs for potential risks in biological system is still elusive to date. In this study, the outstanding reduced graphene quantum dots (rGOQDs) with the QY as high as 24.62% were successfully synthesized by the improved Hummers method and DMF hydrothermal treatment approach. The rGOQDs were N-doped photoluminescent nanomaterials with functional groups on the surface. The fluorescent bio-imaging was performed by exposing zebrafish in different concentrations of the as-prepared rGOQDs, and the distribution of rGOQDs was successfully observed. Moreover, the developmental toxicity and genotoxicity were evaluated to further investigate the potential hazard of rGOQDs. The result indicated that rGOQDs were responsible for the dose-dependent abnormalities on the development of zebrafish. Since the real-time polymerase chain reaction (RT-PCR) results showed that the expression of cyp1a was the highest expression in the selected genes and significantly up-regulated 8.49 fold in zebrafish, the perturbation of rGOQDs on aryl hydrocarbon receptor (AhR) pathway was investigated by using the Tg(cyp1a:gfp) zebrafish for the first time. The results demonstrated that rGOQDs significantly increased the green fluorescent protein (GFP) expression promoted by cyp1a in a dose-dependent manner, which was also further confirmed by the western blotting. This study offered an opportunity to reveal the potential hazards of in vivo bio-probes, which provided a valuable reference for investigating the graphene-based materials on the disturbance of AhR pathway in biological organisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Immunological characterization of the aryl hydrocarbon receptor (AHR) knockout rat in the presence and absence of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

    International Nuclear Information System (INIS)

    Phadnis-Moghe, Ashwini S.; Chen, Weimin; Li, Jinpeng; Crawford, Robert B.; Bach, Anthony; D’Ingillo, Shawna; Kovalova, Natalia; Suarez-Martinez, Jose E.; Kaplan, Barbara L.F.; Harrill, Joshua A.; Budinsky, Robert; Rowlands, J. Craig; Thomas, Russell S.

    2016-01-01

    The aryl hydrocarbon receptor (AHR) has been extensively characterized for the essential role it plays in mediating the toxic responses elicited by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Despite similarities across animal species, species-specific differences exist in the profile of toxicity and sensitivity to TCDD owing, in part, to differences in the AHR. Newer reports have implicated the importance of AHR in the development and regulation of the immune system. Our present studies seek to further explore the essential role of AHR in lymphoid tissue composition, B cell function and the immunological responses after TCDD administration using the recently established AHR KO rats. Comprehensive immune cell phenotyping showed a decrease in the CD8 + T cell, CD11c + populations and an increase in NKT cells in 3-week-old AHR KO rats compared to the WT controls. The lipopolysaccharide-induced IgM response and proliferation was markedly suppressed in the WT but not in the AHR KO B cells in the presence of TCDD. However, the percentage of LPS-activated IgM + B cells was significantly higher in the AHR KO B cells as compared to that of WT suggesting the role of AHR in regulating the IgM response. The use of an AHR antagonist further alluded to the endogenous role of AHR in regulating B cell responses in the rat. Overall, the studies report for the first time, comprehensive immune cell phenotyping of the AHR KO rat and the endogenous role of AHR in the regulation of B cell function in the rat.

  1. Reactivation of estrogen receptor α by vorinostat sensitizes mesenchymal-like triple-negative breast cancer to aminoflavone, a ligand of the aryl hydrocarbon receptor.

    Science.gov (United States)

    Stark, Karri; Burger, Angelika; Wu, Jianmei; Shelton, Phillip; Polin, Lisa; Li, Jing

    2013-01-01

    Aminoflavone (AF) acts as a ligand of the aryl hydrocarbon receptor (AhR). Expression of estrogen receptor α (ERα) and AhR-mediated transcriptional induction of CYP1A1 can sensitize breast cancer cells to AF. The objective of this study was to investigate the combined antitumor effect of AF and the histone deacetylase inhibitor vorinostat for treating mesenchymal-like triple-negative breast cancer (TNBC) as well as the underlying mechanisms of such treatment. In vitro antiproliferative activity of AFP464 (AF prodrug) in breast cancer cell lines was evaluated by MTS assay. In vitro, the combined effect of AFP464 and vorinostat on cell proliferation was assessed by the Chou-Talalay method. In vivo, antitumor activity of AFP464, given alone and in combination with vorinostat, was studied using TNBC xenograft models. Knockdown of ERα was performed using specific, small-interfering RNA. Western blot, quantitative RT-PCR, immunofluorescence, and immunohistochemical staining were performed to study the mechanisms underlying the combined antitumor effect. Luminal and basal A subtype breast cancer cell lines were sensitive to AFP464, whereas basal B subtype or mesenchymal-like TNBC cells were resistant. Vorinostat sensitized mesenchymal-like TNBC MDA-MB-231 and Hs578T cells to AFP464. It also potentiated the antitumor activity of AFP464 in a xenograft model using MDA-MB-231 cells. In vitro and in vivo mechanistic studies suggested that vorinostat reactivated ERα expression and restored AhR-mediated transcriptional induction of CYP1A1. The response of breast cancer cells to AF or AFP464 was associated with their gene expression profile. Vorinostat sensitized mesenchymal-like TNBC to AF, at least in part, by reactivating ERα expression and restoring the responsiveness of AhR to AF.

  2. Diphenylarsinic acid, a chemical warfare-related neurotoxicant, promotes liver carcinogenesis via activation of aryl hydrocarbon receptor signaling and consequent induction of oxidative DAN damage in rats

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Min; Yamada, Takanori; Yamano, Shotaro; Kato, Minoru; Kakehashi, Anna; Fujioka, Masaki; Tago, Yoshiyuki; Kitano, Mistuaki; Wanibuchi, Hideki, E-mail: wani@med.osaka-cu.ac.jp

    2013-11-15

    Diphenylarsinic acid (DPAA), a chemical warfare-related neurotoxic organic arsenical, is present in the groundwater and soil in some regions of Japan due to illegal dumping after World War II. Inorganic arsenic is carcinogenic in humans and its organic arsenic metabolites are carcinogenic in animal studies, raising serious concerns about the carcinogenicity of DPAA. However, the carcinogenic potential of DPAA has not yet been evaluated. In the present study we found that DPAA significantly enhanced the development of diethylnitrosamine-induced preneoplastic lesions in the liver in a medium-term rat liver carcinogenesis assay. Evaluation of the expression of cytochrome P450 (CYP) enzymes in the liver revealed that DPAA induced the expression of CYP1B1, but not any other CYP1, CYP2, or CYP3 enzymes, suggesting that CYP1B1 might be the enzyme responsible for the metabolic activation of DPAA. We also found increased oxidative DNA damage, possibly due to elevated CYP1B1 expression. Induction of CYP1B1 has generally been linked with the activation of AhR, and we found that DPAA activates the aryl hydrocarbon receptor (AhR). Importantly, the promotion effect of DPAA was observed only at a dose that activated the AhR, suggesting that activation of AhR and consequent induction of AhR target genes and oxidative DNA damage plays a vital role in the promotion effects of DPAA. The present study provides, for the first time, evidence regarding the carcinogenicity of DPAA and indicates the necessity of comprehensive evaluation of its carcinogenic potential using long-term carcinogenicity studies. - Highlights: • DPAA, an environmental neurotoxicant, promotes liver carcinogenesis in rats. • DPAA is an activator of AhR signaling pathway. • DPAA promoted oxidative DNA damage in rat livers. • AhR target gene CYP 1B1 might be involved in the metabolism of DPAA.

  3. Loss of aryl hydrocarbon receptor promotes gene changes associated with premature hematopoietic stem cell exhaustion and development of a myeloproliferative disorder in aging mice.

    Science.gov (United States)

    Singh, Kameshwar P; Bennett, John A; Casado, Fanny L; Walrath, Jason L; Welle, Stephen L; Gasiewicz, Thomas A

    2014-01-15

    Loss of immune function and increased hematopoietic disease are among the most clinically significant consequences of aging. Hematopoietic stem cells (HSCs) from mice lacking aryl hydrocarbon receptor (AhR) have high rates of cell division. Studies were designed to test the hypothesis that aging AhR-null allele (AhR-KO) mice develop premature HSC exhaustion, and changes leading to hematological disease. Compared to wild-type, aging AhR-KO mice showed a decreased survival rate, splenomegaly, increased circulating white blood cells, hematopoietic cell accumulation in tissues, and anemia. Analysis of bone marrow indicated increased numbers of stem/progenitor and lineage-committed cells, but decreased erythroid progenitors. There was also decreased self-renewal capacity of HSCs determined by competitive repopulation and serial transplantation. HSCs also showed increased levels of reactive oxygen species (ROS), Ki-67, and γ-H2A.X, but decreased p16(Ink4a). Splenic cells from aging KO mice had abnormal expression of genes, including Gata-1, Sh2d3c, Gfi-1, p21, and c-myc, involved in trafficking and associated with leukemia. HSCs from AhR-KO mice had gene changes related to HSC maintenance and consistent with phenotype observed. The most prominent gene changes (overexpression of Srpk2, Creb1, Hes1, mtor, pdp1) have been associated with HSC hyperproliferation, leukemia, and accelerated aging. Pathway analyses also indicated an enrichment of genes associated with oxidative stress, acute myelogenous leukemia, aging, and heat shock response, and the β-catenin/Wnt pathways. These data indicate that loss of AhR and associated changes in multiple signaling pathways promote premature HSC exhaustion and development of a myeloproliferative disorder. They also implicate a critical role of the AhR in the regulation of HSCs.

  4. TRIGGER

    CERN Multimedia

    Wesley Smith

    Level-1 Trigger Hardware and Software The trigger synchronization procedures for running with cosmic muons and operating with the LHC were reviewed during the May electronics week. Firmware maintenance issues were also reviewed. Link tests between the new ECAL endcap trigger concentrator cards (TCC48) and the Regional Calorimeter Trigger have been performed. Firmware for the energy sum triggers and an upgraded tau trigger of the Global Calorimeter Triggers has been developed and is under test. The optical fiber receiver boards for the Track-Finder trigger theta links of the DT chambers are now all installed. The RPC trigger is being made more robust by additional chamber and cable shielding and also by firmware upgrades. For the CSC’s the front-end and trigger motherboard firmware have been updated. New RPC patterns and DT/CSC lookup tables taking into account phi asymmetries in the magnetic field configuration are under study. The motherboard for the new pipeline synchronizer of the Global Trigg...

  5. TRIGGER

    CERN Multimedia

    W. Smith

    2012-01-01

      Level-1 Trigger The Level-1 Trigger group is ready to deploy improvements to the L1 Trigger algorithms for 2012. These include new high-PT patterns for the RPC endcap, an improved CSC PT assignment, a new PT-matching algorithm for the Global Muon Trigger, and new calibrations for ECAL, HCAL, and the Regional Calorimeter Trigger. These should improve the efficiency, rate, and stability of the L1 Trigger. The L1 Trigger group also is migrating the online systems to SLC5. To make the data transfer from the Global Calorimeter Trigger to the Global Trigger more reliable and also to allow checking the data integrity online, a new optical link system has been developed by the GCT and GT groups and successfully tested at the CMS electronics integration facility in building 904. This new system is now undergoing further tests at Point 5 before being deployed for data-taking this year. New L1 trigger menus have recently been studied and proposed by Emmanuelle Perez and the L1 Detector Performance Group...

  6. TRIGGER

    CERN Multimedia

    W. Smith

    At the March meeting, the CMS trigger group reported on progress in production, tests in the Electronics Integration Center (EIC) in Prevessin 904, progress on trigger installation in the underground counting room at point 5, USC55, the program of trigger pattern tests and vertical slice tests and planning for the Global Runs starting this summer. The trigger group is engaged in the final stages of production testing, systems integration, and software and firmware development. Most systems are delivering final tested electronics to CERN. The installation in USC55 is underway and integration testing is in full swing. A program of orderly connection and checkout with subsystems and central systems has been developed. This program includes a series of vertical subsystem slice tests providing validation of a portion of each subsystem from front-end electronics through the trigger and DAQ to data captured and stored. After full checkout, trigger subsystems will be then operated in the CMS Global Runs. Continuous...

  7. Activation of the aryl hydrocarbon receptor is the major toxic mode of action of an organic extract of a reference urban dust particulate matter mixture: The role of polycyclic aromatic hydrocarbons

    International Nuclear Information System (INIS)

    Andrysik, Zdenek; Vondracek, Jan; Marvanova, Sona; Ciganek, Miroslav; Neca, Jiri; Pencikova, Katerina; Mahadevan, Brinda; Topinka, Jan; Baird, William M.; Kozubik, Alois; Machala, Miroslav

    2011-01-01

    Highlights: → SRM1649a extract and its fractions are potent activators of AhR in a model of epithelial cells. → AhR-dependent effects include both induction of CYP1 enzymes and disruption of cell proliferation control. → Polycyclic aromatic hydrocarbons present in the neutral SRM1649a fraction are major contributors to the AhR-mediated toxic effects. → Activation of AhR and related nongenotoxic effects occur at significantly lower doses than the formation of DNA adducts and activation of DNA damage response. → More attention should be paid to the AhR-dependent nongenotoxic events elicited by urban particulate matter constituents. - Abstract: Many of the toxic and carcinogenic effects of urban air pollution have been linked to polycyclic aromatic hydrocarbons (PAHs) adsorbed to airborne particulate matter (PM). The carcinogenic properties of PAHs in complex organic mixtures derived from PM have been chiefly attributed to their mutagenicity. Nevertheless, PAHs are also potent activators of the aryl hydrocarbon receptor (AhR), which may contribute to their nongenotoxic effects, including tumor promotion. As the genotoxicity of carcinogenic PAHs in complex mixtures derived from urban PM is often inhibited by other mixture constituents, the AhR-mediated activity of urban PM extracts might significantly contribute to the carcinogenic activity of such mixtures. In the present study, we used an organic extract of the urban dust standard reference material, SRM1649a, as a model mixture to study a range of toxic effects related to DNA damage and AhR activation. Both the organic extract and its neutral aromatic fraction formed a low number of DNA adducts per nucleotide in the liver epithelial WB-F344 cells model, without inducing DNA damage response, such as tumor suppressor p53 activation and apoptosis. In contrast, we found that this extract, as well as its neutral and polar fractions, were potent inducers of a range of AhR-mediated responses, including induction

  8. TRIGGER

    CERN Multimedia

    by Wesley Smith

    2010-01-01

    Level-1 Trigger Hardware and Software The overall status of the L1 trigger has been excellent and the running efficiency has been high during physics fills. The timing is good to about 1%. The fine-tuning of the time synchronization of muon triggers is ongoing and will be completed after more than 10 nb-1 of data have been recorded. The CSC trigger primitive and RPC trigger timing have been refined. A new configuration for the CSC Track Finder featured modified beam halo cuts and improved ghost cancellation logic. More direct control was provided for the DT opto-receivers. New RPC Cosmic Trigger (RBC/TTU) trigger algorithms were enabled for collision runs. There is further work planned during the next technical stop to investigate a few of the links from the ECAL to the Regional Calorimeter Trigger (RCT). New firmware and a new configuration to handle trigger rate spikes in the ECAL barrel are also being tested. A board newly developed by the tracker group (ReTRI) has been installed and activated to block re...

  9. TRIGGER

    CERN Multimedia

    Wesley Smith

    Level-1 Trigger Hardware and Software The production of the trigger hardware is now basically finished, and in time for the turn-on of the LHC. The last boards produced are the Trigger Concentrator Cards for the ECAL Endcaps (TCC-EE). After the recent installation of the four EE Dees, the TCC-EE prototypes were used for their commissioning. Production boards are arriving and are being tested continuously, with the last ones expected in November. The Regional Calorimeter Trigger hardware is fully integrated after installation of the last EE cables. Pattern tests from the HCAL up to the GCT have been performed successfully. The HCAL triggers are fully operational, including the connection of the HCAL-outer and forward-HCAL (HO/HF) technical triggers to the Global Trigger. The HCAL Trigger and Readout (HTR) board firmware has been updated to permit recording of the tower “feature bit” in the data. The Global Calorimeter Trigger hardware is installed, but some firmware developments are still n...

  10. TRIGGER

    CERN Multimedia

    W. Smith

    2010-01-01

    Level-1 Trigger Hardware and Software The Level-1 Trigger hardware has performed well during both the recent proton-proton and heavy ion running. Efforts were made to improve the visibility and handling of alarms and warnings. The tracker ReTRI boards that prevent fixed frequencies of Level-1 Triggers are now configured through the Trigger Supervisor. The Global Calorimeter Trigger (GCT) team has introduced a buffer cleanup procedure at stops and a reset of the QPLL during configuring to ensure recalibration in case of a switch from the LHC clock to the local clock. A device to test the cables between the Regional Calorimeter Trigger and the GCT has been manufactured. A wrong charge bit was fixed in the CSC Trigger. The ECAL group is improving crystal masking and spike suppression in the trigger primitives. New firmware for the Drift Tube Track Finder (DTTF) sorters was developed to improve fake track tagging and sorting. Zero suppression was implemented in the DT Sector Collector readout. The track finder b...

  11. TRIGGER

    CERN Multimedia

    Wesley Smith

    Trigger Hardware The status of the trigger components was presented during the September CMS Week and Annual Review and at the monthly trigger meetings in October and November. Procedures for cold and warm starts (e.g. refreshing of trigger parameters stored in registers) of the trigger subsystems have been studied. Reviews of parts of the Global Calorimeter Trigger (GCT) and the Global Trigger (GT) have taken place in October and November. The CERN group summarized the status of the Trigger Timing and Control (TTC) system. All TTC crates and boards are installed in the underground counting room, USC55. The central clock system will be upgraded in December (after the Global Run at the end of November GREN) to the new RF2TTC LHC machine interface timing module. Migration of subsystem's TTC PCs to SLC4/ XDAQ 3.12 is being prepared. Work is on going to unify the access to Local Timing Control (LTC) and TTC CMS interface module (TTCci) via SOAP (Simple Object Access Protocol, a lightweight XML-based messaging ...

  12. Aryl hydrocarbon receptor (AhR agonists suppress interleukin-6 expression by bone marrow stromal cells: an immunotoxicology study

    Directory of Open Access Journals (Sweden)

    Schlezinger Jennifer J

    2003-12-01

    Full Text Available Abstract Background Bone marrow stromal cells produce cytokines required for the normal growth and development of all eight hematopoietic cell lineages. Aberrant cytokine production by stromal cells contributes to blood cell dyscrasias. Consequently, factors that alter stromal cell cytokine production may significantly compromise the development of normal blood cells. We have shown that environmental chemicals, such as aromatic hydrocarbon receptor (AhR agonists, suppress B lymphopoiesis by modulating bone marrow stromal cell function. Here, we extend these studies to evaluate the potential for two prototypic AhR agonists, 7,12-dimethylbenz [a]anthracene (DMBA and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, to alter stromal cell cytokine responses. Methods Bone marrow stromal cells were treated with AhR agonists and bacterial lipopolysaccharide (LPS to mimic innate inflammatory cytokine responses and to study the effects of AhR ligands on those responses. Steady state cytokine RNA levels were screened by RNAse protection assays (RPA and quantified by real-time PCR. Cytokine (IL-6 protein production was measured by ELISA. NF-κB EMSAs were used to study IL-6 transcriptional regulation. Results RPAs indicated that AhR+ bone marrow stromal cells consistently up-regulated genes encoding IL-6 and LIF in response to LPS, presumably through activation of Toll-like receptor 4. Pre-treatment with low doses of DMBA or TCDD selectively abrogated IL-6 gene induction but had no effect on LIF mRNA. Real-time-PCR indicated a significant inhibition of IL-6 mRNA by AhR ligands within 1 hour of LPS challenge which was reflected in a profound down-regulation of IL-6 protein induction, with DMBA and TCDD suppressing IL-6 levels as much as 65% and 88%, respectively. This potent inhibitory effect persisted for at least 72 hours. EMSAs measuring NF-κB binding to IL-6 promoter sequences, an event known to induce IL-6 transcription, indicated a significant decrease in

  13. TRIGGER

    CERN Multimedia

    W. Smith from contributions of C. Leonidopoulos

    2010-01-01

    Level-1 Trigger Hardware and Software Since nearly all of the Level-1 (L1) Trigger hardware at Point 5 has been commissioned, activities during the past months focused on the fine-tuning of synchronization, particularly for the ECAL and the CSC systems, on firmware upgrades and on improving trigger operation and monitoring. Periodic resynchronizations or hard resets and a shortened luminosity section interval of 23 seconds were implemented. For the DT sector collectors, an automatic power-off was installed in case of high temperatures, and the monitoring capabilities of the opto-receivers and the mini-crates were enhanced. The DTTF and the CSCTF now have improved memory lookup tables. The HCAL trigger primitive logic implemented a new algorithm providing better stability of the energy measurement in the presence of any phase misalignment. For the Global Calorimeter Trigger, additional Source Cards have been manufactured and tested. Testing of the new tau, missing ET and missing HT algorithms is underw...

  14. Persistent Organic Pollutants Modify Gut Microbiota-Host Metabolic Homeostasis in Mice Through Aryl Hydrocarbon Receptor Activation.

    Science.gov (United States)

    Zhang, Limin; Nichols, Robert G; Correll, Jared; Murray, Iain A; Tanaka, Naoki; Smith, Philip B; Hubbard, Troy D; Sebastian, Aswathy; Albert, Istvan; Hatzakis, Emmanuel; Gonzalez, Frank J; Perdew, Gary H; Patterson, Andrew D

    2015-07-01

    Alteration of the gut microbiota through diet and environmental contaminants may disturb physiological homeostasis, leading to various diseases including obesity and type 2 diabetes. Because most exposure to environmentally persistent organic pollutants (POPs) occurs through the diet, the host gastrointestinal tract and commensal gut microbiota are likely to be exposed to POPs. We examined the effect of 2,3,7,8-tetrachlorodibenzofuran (TCDF), a persistent environmental contaminant, on gut microbiota and host metabolism, and we examined correlations between gut microbiota composition and signaling pathways. Six-week-old male wild-type and Ahr-/- mice on the C57BL/6J background were treated with 24 μg/kg TCDF in the diet for 5 days. We used 16S rRNA gene sequencing, 1H nuclear magnetic resonance (NMR) metabolomics, targeted ultra-performance liquid chromatography coupled with triplequadrupole mass spectrometry, and biochemical assays to determine the microbiota compositions and the physiological and metabolic effects of TCDF. Dietary TCDF altered the gut microbiota by shifting the ratio of Firmicutes to Bacteroidetes. TCDF-treated mouse cecal contents were enriched with Butyrivibrio spp. but depleted in Oscillobacter spp. compared with vehicle-treated mice. These changes in the gut microbiota were associated with altered bile acid metabolism. Further, dietary TCDF inhibited the farnesoid X receptor (FXR) signaling pathway, triggered significant inflammation and host metabolic disorders as a result of activation of bacterial fermentation, and altered hepatic lipogenesis, gluconeogenesis, and glycogenolysis in an AHR-dependent manner. These findings provide new insights into the biochemical consequences of TCDF exposure involving the alteration of the gut microbiota, modulation of nuclear receptor signaling, and disruption of host metabolism.

  15. TRIGGER

    CERN Multimedia

    W. Smith

    Level-1 Trigger Hardware and Software The trigger system has been constantly in use in cosmic and commissioning data taking periods. During CRAFT running it delivered 300 million muon and calorimeter triggers to CMS. It has performed stably and reliably. During the abort gaps it has also provided laser and other calibration triggers. Timing issues, namely synchronization and latency issues, have been solved. About half of the Trigger Concentrator Cards for the ECAL Endcap (TCC-EE) are installed, and the firmware is being worked on. The production of the other half has started. The HCAL Trigger and Readout (HTR) card firmware has been updated, and new features such as fast parallel zero-suppression have been included. Repairs of drift tube (DT) trigger mini-crates, optical links and receivers of sector collectors are under way and have been completed on YB0. New firmware for the optical receivers of the theta links to the drift tube track finder is being installed. In parallel, tests with new eta track finde...

  16. TRIGGER

    CERN Multimedia

    R. Carlin with contributions from D. Acosta

    2012-01-01

    Level-1 Trigger Data-taking continues at cruising speed, with high availability of all components of the Level-1 trigger. We have operated the trigger up to a luminosity of 7.6E33, where we approached 100 kHz using the 7E33 prescale column.  Recently, the pause without triggers in case of an automatic "RESYNC" signal (the "settle" and "recover" time) was reduced in order to minimise the overall dead-time. This may become very important when the LHC comes back with higher energy and luminosity after LS1. We are also preparing for data-taking in the proton-lead run in early 2013. The CASTOR detector will make its comeback into CMS and triggering capabilities are being prepared for this. Steps to be taken include improved cooperation with the TOTEM trigger system and using the LHC clock during the injection and ramp phases of LHC. Studies are being finalised that will have a bearing on the Trigger Technical Design Report (TDR), which is to be rea...

  17. TRIGGER

    CERN Multimedia

    Wesley Smith

    Level-1 Trigger Hardware and Software The final parts of the Level-1 trigger hardware are now being put in place. For the ECAL endcaps, more than half of the Trigger Concentrator Cards for the ECAL Endcap (TCC-EE) are now available at CERN, such that one complete endcap can be covered. The Global Trigger now correctly handles ECAL calibration sequences, without being influenced by backpressure. The Regional Calorimeter Trigger (RCT) hardware is complete and working in USC55. Intra-crate tests of all 18 RCT crates and the Global Calorimeter Trigger (GCT) are regularly taking place. Pattern tests have successfully captured data from HCAL through RCT to the GCT Source Cards. HB/HE trigger data are being compared with emulator results to track down the very few remaining hardware problems. The treatment of hot and dead cells, including their recording in the database, has been defined. For the GCT, excellent agreement between the emulator and data has been achieved for jets and HF ET sums. There is still som...

  18. TRIGGER

    CERN Multimedia

    W. Smith

    At the December meeting, the CMS trigger group reported on progress in production, tests in the Electronics Integration Center (EIC) in Prevessin 904, progress on trigger installation in the underground counting room at point 5, USC55, and results from the Magnet Test and Cosmic Challenge (MTCC) phase II. The trigger group is engaged in the final stages of production testing, systems integration, and software and firmware development. Most systems are delivering final tested electronics to CERN. The installation in USC55 is underway and moving towards integration testing. A program of orderly connection and checkout with subsystems and central systems has been developed. This program includes a series of vertical subsystem slice tests providing validation of a portion of each subsystem from front-end electronics through the trigger and DAQ to data captured and stored. This is combined with operations and testing without beam that will continue until startup. The plans for start-up, pilot and early running tri...

  19. TRIGGER

    CERN Multimedia

    W. Smith, from contributions of D. Acosta

    2012-01-01

      The L1 Trigger group deployed several major improvements this year. Compared to 2011, the single-muon trigger rate has been reduced by a factor of 2 and the η coverage has been restored to 2.4, with high efficiency. During the current technical stop, a higher jet seed threshold will be applied in the Global Calorimeter Trigger in order to significantly reduce the strong pile-up dependence of the HT and multi-jet triggers. The currently deployed L1 menu, with the “6E33” prescales, has a total rate of less than 100 kHz and operates with detector readout dead time of less than 3% for luminosities up to 6.5 × 1033 cm–2s–1. Further prescale sets have been created for 7 and 8 × 1033 cm–2s–1 luminosities. The L1 DPG is evaluating the performance of the Trigger for upcoming conferences and publication. Progress on the Trigger upgrade was reviewed during the May Upgrade Week. We are investigating scenarios for stagin...

  20. TRIGGER

    CERN Multimedia

    Wesley Smith

    2011-01-01

    Level-1 Trigger Hardware and Software New Forward Scintillating Counters (FSC) for rapidity gap measurements have been installed and integrated into the Trigger recently. For the Global Muon Trigger, tuning of quality criteria has led to improvements in muon trigger efficiencies. Several subsystems have started campaigns to increase spares by recovering boards or producing new ones. The barrel muon sector collector test system has been reactivated, new η track finder boards are in production, and φ track finder boards are under revision. In the CSC track finder, an η asymmetry problem has been corrected. New pT look-up tables have also improved efficiency. RPC patterns were changed from four out of six coincident layers to three out of six in the barrel, which led to a significant increase in efficiency. A new PAC firmware to trigger on heavy stable charged particles allows looking for chamber hit coincidences in two consecutive bunch-crossings. The redesign of the L1 Trigger Emulator...

  1. TRIGGER

    CERN Multimedia

    R. Arcidiacono

    2013-01-01

      In 2013 the Trigger Studies Group (TSG) has been restructured in three sub-groups: STEAM, for the development of new HLT menus and monitoring their performance; STORM, for the development of HLT tools, code and actual configurations; and FOG, responsible for the online operations of the High Level Trigger. The Strategy for Trigger Evolution And Monitoring (STEAM) group is responsible for Trigger Menu development, path timing, trigger performance studies coordination, HLT offline DQM as well as HLT release, menu and conditions validation – in collaboration and with the technical support of the PdmV group. Since the end of proton-proton data taking, the group has started preparing for 2015 data taking, with collisions at 13 TeV and 25 ns bunch spacing. The reliability of the extrapolation to higher energy is being evaluated comparing the trigger rates on 7 and 8 TeV Monte Carlo samples with the data taken in the past two years. The effect of 25 ns bunch spacing is being studied on the d...

  2. TRIGGER

    CERN Multimedia

    W. Smith from contributions of C. Leonidopoulos, I. Mikulec, J. Varela and C. Wulz.

    Level-1 Trigger Hardware and Software Over the past few months, the Level-1 trigger has successfully recorded data with cosmic rays over long continuous stretches as well as LHC splash events, beam halo, and collision events. The L1 trigger hardware, firmware, synchronization, performance and readiness for beam operation were reviewed in October. All L1 trigger hardware is now installed at Point 5, and most of it is completely commissioned. While the barrel ECAL Trigger Concentrator Cards are fully operational, the recently delivered endcap ECAL TCC system is still being commissioned. For most systems there is a sufficient number of spares available, but for a few systems additional reserve modules are needed. It was decided to increase the overall L1 latency by three bunch crossings to increase the safety margin for trigger timing adjustments. In order for CMS to continue data taking during LHC frequency ramps, the clock distribution tree needs to be reset. The procedures for this have been tested. A repl...

  3. TRIGGER

    CERN Multimedia

    W. Smith

    Level-1 Trigger Hardware and Software The road map for the final commissioning of the level-1 trigger system has been set. The software for the trigger subsystems is being upgraded to run under CERN Scientific Linux 4 (SLC4). There is also a new release for the Trigger Supervisor (TS 1.4), which implies upgrade work by the subsystems. As reported by the CERN group, a campaign to tidy the Trigger Timing and Control (TTC) racks has begun. The machine interface was upgraded by installing the new RF2TTC module, which receives RF signals from LHC Point 4. Two Beam Synchronous Timing (BST) signals, one for each beam, can now be received in CMS. The machine group will define the exact format of the information content shortly. The margin on the locking range of the CMS QPLL is planned for study for different subsystems in the next Global Runs, using a function generator. The TTC software has been successfully tested on SLC4. Some TTC subsystems have already been upgraded to SLC4. The TTCci Trigger Supervisor ...

  4. Metformin suppresses CYP1A1 and CYP1B1 expression in breast cancer cells by down-regulating aryl hydrocarbon receptor expression

    Energy Technology Data Exchange (ETDEWEB)

    Do, Minh Truong; Kim, Hyung Gyun; Tran, Thi Thu Phuong; Khanal, Tilak; Choi, Jae Ho [Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon (Korea, Republic of); Chung, Young Chul [Department of Food Science and Culinary, International University of Korea, Jinju (Korea, Republic of); Jeong, Tae Cheon, E-mail: taecheon@ynu.ac.kr [College of Pharmacy, Yeungnam University, Gyeongsan (Korea, Republic of); Jeong, Hye Gwang, E-mail: hgjeong@cnu.ac.kr [Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon (Korea, Republic of)

    2014-10-01

    Induction of cytochrome P450 (CYP) 1A1 and CYP1B1 by environmental xenobiotic chemicals or endogenous ligands through the activation of the aryl hydrocarbon receptor (AhR) has been implicated in a variety of cellular processes related to cancer, such as transformation and tumorigenesis. Here, we investigated the effects of the anti-diabetes drug metformin on expression of CYP1A1 and CYP1B1 in breast cancer cells under constitutive and inducible conditions. Our results indicated that metformin down-regulated the expression of CYP1A1 and CYP1B1 in breast cancer cells under constitutive and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced conditions. Down-regulation of AhR expression was required for metformin-mediated decreases in CYP1A1 and CYP1B1 expression, and the metformin-mediated CYP1A1 and CYP1B1 reduction is irrelevant to estrogen receptor α (ERα) signaling. Furthermore, we found that metformin markedly down-regulated Sp1 protein levels in breast cancer cells. The use of genetic and pharmacological tools revealed that metformin-mediated down-regulation of AhR expression was mediated through the reduction of Sp1 protein. Metformin inhibited endogenous AhR ligand-induced CYP1A1 and CYP1B1 expression by suppressing tryptophan-2,3-dioxygenase (TDO) expression in MCF-7 cells. Finally, metformin inhibits TDO expression through a down-regulation of Sp1 and glucocorticoid receptor (GR) protein levels. Our findings demonstrate that metformin reduces CYP1A1 and CYP1B1 expression in breast cancer cells by down-regulating AhR signaling. Metformin would be able to act as a potential chemopreventive agent against CYP1A1 and CYP1B1-mediated carcinogenesis and development of cancer. - Graphical abstract: Schematic of the CYP1A1 and CYP1B1 gene regulation by metformin. - Highlights: • Metformin inhibits CYP1A1 and CYP1B1 expression. • Metformin down-regulates the AhR signaling. • Metformin reduces Sp1 protein expression. • Metformin suppresses TDO expression.

  5. Aryl hydrocarbon receptor is necessary to protect fetal human pulmonary microvascular endothelial cells against hyperoxic injury: Mechanistic roles of antioxidant enzymes and RelB

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Shaojie; Patel, Ananddeep; Chu, Chun; Jiang, Weiwu; Wang, Lihua; Welty, Stephen E.; Moorthy, Bhagavatula; Shivanna, Binoy, E-mail: shivanna@bcm.edu

    2015-07-15

    Hyperoxia contributes to the development of bronchopulmonary dysplasia (BPD) in premature infants. Activation of the aryl hydrocarbon receptor (AhR) protects adult and newborn mice against hyperoxic lung injury by mediating increases in the expression of phase I (cytochrome P450 (CYP) 1A) and phase II (NADP(H) quinone oxidoreductase (NQO1)) antioxidant enzymes (AOE). AhR positively regulates the expression of RelB, a component of the nuclear factor-kappaB (NF-κB) protein that contributes to anti-inflammatory processes in adult animals. Whether AhR regulates the expression of AOE and RelB, and protects fetal primary human lung cells against hyperoxic injury is unknown. Therefore, we tested the hypothesis that AhR-deficient fetal human pulmonary microvascular endothelial cells (HPMEC) will have decreased RelB activation and AOE, which will in turn predispose them to increased oxidative stress, inflammation, and cell death compared to AhR-sufficient HPMEC upon exposure to hyperoxia. AhR-deficient HPMEC showed increased hyperoxia-induced reactive oxygen species (ROS) generation, cleavage of poly(ADP-ribose) polymerase (PARP), and cell death compared to AhR-sufficient HPMEC. Additionally, AhR-deficient cell culture supernatants displayed increased macrophage inflammatory protein 1α and 1β, indicating a heightened inflammatory state. Interestingly, loss of AhR was associated with a significantly attenuated CYP1A1, NQO1, superoxide dismutase 1(SOD1), and nuclear RelB protein expression. These findings support the hypothesis that decreased RelB activation and AOE in AhR-deficient cells is associated with increased hyperoxic injury compared to AhR-sufficient cells. - Highlights: • AhR deficiency potentiates oxygen toxicity in human fetal lung cells. • Deficient AhR signaling increases hyperoxia-induced cell death. • AhR deficiency increases hyperoxia-induced ROS generation and inflammation. • Anti-oxidant enzyme levels are attenuated in AhR-deficient lung cells

  6. Up-regulation of osteopontin expression by aryl hydrocarbon receptor via both ligand-dependent and ligand-independent pathways in lung cancer.

    Science.gov (United States)

    Chuang, Cheng-Yen; Chang, Han; Lin, Pinpin; Sun, Shih-Jung; Chen, Po-Hung; Lin, Yu-Ying; Sheu, Gwo-Tarng; Ko, Jiunn-Liang; Hsu, Shih-Lan; Chang, Jinghua Tsai

    2012-01-15

    The secreted glycol-phosphoprotein OPN not only plays important roles in immune responses and tissue remodeling but is also intimately involved in tumorigenesis. It is up-regulated in various cancers and correlated with poor prognosis. It is evident by enhancing growth and migration of cancer cells. However, the mechanisms that participate in up-regulation of OPN in lung cancer are largely unknown. Up-regulation of aryl hydrocarbon receptor (AhR), a transcription factor activated by xenobiotics, has been observed in lung cancer as well as premalignant lesions. In this study we demonstrated that AhR positively regulates OPN expression in lung cancer. We observed positive correlation of OPN and AhR expression in lung cancer specimen. Knockdown or overexpression of AhR exhibited down- or up-regulation of OPN expression in lung cancer cells. We identified an OPN promoter region between positions -268 and +435 that was activated by both ligand-independent and ligand-activated AhR. However, this region does not contain AhR response element/dioxin response element (DRE/XRE). Further truncations and internal deletions of the promoter revealed that the ligand-independent and ligand-activated AhR function through different regions of OPN promoter. The region between -268 and -100 was required for ligand-independent AhR activity. This region contains several cis-elements including AP2, C/EBP, SP1 and AP1 sites. On the other hand, the ligand-activated AhR up-regulates OPN activity through two regions of OPN promoter; one contains NFκB site at +137 and the other is between positions -100 and +126. This study suggested that both overexpression of un-induced AhR (in cases of non-smokers with high level of AhR) and ligand-activated AhR (such as smokers) contribute to up-regulation of OPN that in turn leads to lung tumorigenesis. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. The aryl hydrocarbon receptor and estrogen receptor alpha differentially modulate nuclear factor erythroid-2-related factor 2 transactivation in MCF-7 breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Lo, Raymond; Matthews, Jason, E-mail: jason.matthews@utoronto.ca

    2013-07-15

    Nuclear factor erythroid-2-related factor 2 (NRF2; NFE2L2) plays an important role in mediating cellular protection against reactive oxygen species. NRF2 signaling is positively modulated by the aryl hydrocarbon receptor (AHR) but inhibited by estrogen receptor alpha (ERα). In this study we investigated the crosstalk among NRF2, AHR and ERα in MCF-7 breast cancer cells treated with the NRF2 activator sulforaphane (SFN), a dual AHR and ERα activator, 3,3′-diindolylmethane (DIM), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 17β-estradiol (E2). SFN-dependent increases in NADPH-dependent oxidoreductase 1 (NQO1) and heme oxygenase I (HMOX1) mRNA levels were significantly reduced after co-treatment with E2. E2-dependent repression of NQO1 and HMOX1 was associated with increased ERα but reduced p300 recruitment and reduced histone H3 acetylation at both genes. In contrast, DIM + SFN or TCDD + SFN induced NQO1 and HMOX1 mRNA expression to levels higher than SFN alone, which was prevented by RNAi-mediated knockdown of AHR. DIM + SFN but not TCDD + SFN also induced recruitment of ERα to NQO1 and HMOX1. However, the presence of AHR at NQO1 and HMOX1 restored p300 recruitment and histone H3 acetylation, thereby reversing the ERα-dependent repression of NRF2. Taken together, our study provides further evidence of functional interplay among NRF2, AHR and ERα signaling pathways through altered p300 recruitment to NRF2-regulated target genes. - Highlights: • We examined crosstalk among ERα, AHR, and NRF2 in MCF-7 breast cancer cells. • AHR enhanced the mRNA expression levels of two NRF2 target genes – HMOX1 and NQO1. • ERα repressed HMOX1 and NQO1 expression via decreased histone acetylation. • AHR prevented ERα-dependent repression of HMOX1 and NQO1.

  8. Aryl hydrocarbon receptors in urogenital sinus mesenchyme mediate the inhibition of prostatic epithelial bud formation by 2,3,7,8-tetrachlorodibenzo-p-dioxin

    International Nuclear Information System (INIS)

    Ko, Kinarm; Moore, Robert W.; Peterson, Richard E.

    2004-01-01

    In utero exposure of male C57BL/6 mice to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) prevents prostatic epithelial buds from forming in the ventral region of the urogenital sinus (UGS) and reduces the number of buds that form in the dorsolateral region. This inhibition of budding is aryl hydrocarbon receptor (AHR) dependent and appears to be the primary cause of lobe-specific prostate abnormalities in TCDD-exposed mice. TCDD can inhibit prostatic epithelial bud formation by acting directly on the UGS in vitro, but whether it does so via AHR in UGS mesenchyme, epithelium, or both was unknown. To address this issue, UGS mesenchyme and epithelium from gestation day (GD) 15 wild-type C57BL/6J male mice were isolated, recombined, and cultured in vitro for 5 days with 10 -8 M 5α-dihydrotestosterone (DHT) and either 10 -9 M TCDD or vehicle. Prostatic epithelial buds were viewed by light microscopy after removal of mesenchyme. Effects depended greatly on which portions of the mesenchyme were used: TCDD had little if any effect when whole UGS epithelium (UGE) was recombined with ventral plus dorsolateral mesenchyme, tended to reduce bud numbers in recombinants made with UGE and dorsolateral mesenchyme, and severely reduced bud numbers in recombinants made with UGE and ventral mesenchyme (VM). [VM + UGE] recombinants prepared from wild-type and AHR knockout (Ahr -/- ) mice were then cultured with DHT to determine the site of action of TCDD. AHR null mutation alone had no effect on budding. TCDD severely inhibited prostatic epithelial bud formation in recombinants that contained mesenchymal AHR, whereas bud formation was not inhibited by TCDD in recombinants lacking mesenchymal AHR, regardless of epithelial AHR status. These results demonstrate that UGS mesenchyme and not UGS epithelium is the site of action of TCDD. Therefore, the initial events responsible for abnormal UGS (and ultimately prostate) development occur within the UGS mesenchyme, and changes in gene expression

  9. Aryl hydrocarbon receptor (AhR-mediated perturbations in gene expression during early stages of CD4+ T-cell differentiation

    Directory of Open Access Journals (Sweden)

    Diana eRohlman

    2012-08-01

    Full Text Available Activation of the aryl hydrocarbon receptor (AhR by its prototypic ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, mediates potent suppression of T-cell dependent immune responses. The suppressive effects of TCDD occur early during CD4+ T-cell differentiation in the absence of effects on proliferation and have recently been associated with the induction of AhR-dependent regulatory T-cells (Treg. Since AhR functions as a ligand-activated transcription factor, changes in gene expression induced by TCDD during the early stages of CD4+ T-cell differentiation are likely to reflect fundamental mechanisms of AhR action. A custom panel of genes associated with T-cell differentiation was used to query changes in gene expression induced by exposure to 1 nM TCDD. CD4+ T-cells from AhR+/+ and AhR-/- mice were cultured with cytokines known to polarize the differentiation of T-cells to various effector lineages. Treatment with TCDD induced expression of Cyp1a1, Cyp1b1 and Ahrr in CD4+ T-cells from AhR+/+ mice under all culture conditions, validating the presence and activation of AhR in these cells. The highest levels of AhR activation occurred under Th17 conditions at 24 hours and Tr1 conditions at 48 hours. Unexpectedly, expression levels of most genes associated with early T-cell differentiation were unaltered by AhR activation, including lineage-specific genes that drive CD4+ T-cell polarization. The major exception was AhR-dependent up-regulation of Il22 that was seen under all culture conditions. Independent of TCDD, AhR down-regulated the expression of Il17a and Rorc based on increased expression of these genes in AhR-deficient cells across culture conditions. These findings are consistent with a role for AhR in down-regulation of inflammatory immune responses and implicate IL-22 as a potential contributor to the immunosuppressive effects of TCDD.

  10. Aryl hydrocarbon receptor pathway activation enhances gastric cancer cell invasiveness likely through a c-Jun-dependent induction of matrix metalloproteinase-9

    Directory of Open Access Journals (Sweden)

    Song Xin

    2009-04-01

    Full Text Available Abstract Background Abberant aryl hydrocarbon receptor (AhR expression and AhR pathway activation are involved in gastric carcinogenesis. However, the relationship between AhR pathway activation and gastric cancer progression is still unclear. In present study, we used 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD, a classic and most potent ligand of AhR, to activate AhR pathway and investigated the effect of AhR pathway activation on human gastric cancer AGS cell invasion and explored the corresponding mechanism. Results To determine whether AhR pathway can be activated in AGS cells, we examined the expression of CYP1A1, a classic target gene of AhR pathway, following TCDD exposure. RT-PCR and western blot analysis showed that both CYP1A1 mRNA and protein expression were increased in a dose-dependent manner following TCDD treatment and AhR antagonist resveratrol (RSV could reverse this TCDD-induced CYP1A1 expression. To determine whether TCDD treatment of AGS cells results in an induction of MMP-9 expression, we detected MMP-9 mRNA using RT-PCR and detected MMP-9 enzymatic activity using gelatin zymography. The results showed that both MMP-9 mRNA expression and enzymatic activity were gradually increased with the concentration increase of TCDD in media and these changes could be reversed by RSV treatment in a dose-dependent manner. To examine whether AhR activation-induced MMP-9 expression and activity in AGS cells results in increased migration and invasion, we performed wound healing migration assay and transwell migration and invasion assay. After TCDD treatment, the migration distance and the migration and invasion abilities of AGS cells were increased with a dose-dependent manner. To demonstrate AhR activation-induced MMP-9 expression is mediated by c-Jun, siRNA transfection was performed to silence c-Jun mRNA in AGS cells. The results showed that MMP-9 mRNA expression and activity in untreated control AGS cells were very weak; After TCDD

  11. Unbalanced expression of aryl hydrocarbon receptor in peripheral blood CCR6+CD4+ and CD4+CD25+T cells of rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Lin Cheng

    Full Text Available ABSTRACT Objective: The goal of this study was to analyze the role of aryl hydrocarbon receptor in peripheral blood CCR6+CD4+ and CD4+CD25+T cells of patients with rheumatoid arthritis. Methods: Flow cytometry was applied to determine the proportion of AhR positive cells in CCR6+CD4+T, CD4+CD25+T and peripheral blood peripheral mononuclear cells from each subject. AhR mRNA and CYP1A1 mRNA relative expression levels were tested by real-time PCR. Results: The percentage of AhR positive cells in peripheral blood mononuclear cells was higher in RA group than that in healthy cases [(35.23 ± 10.71% vs. (18.83 ± 7.32%, p < 0.01]. The expression levels of AhR and CYP1A1 were both increased in patients with RA while compared to controls [(3.71 ± 1.63 vs. (2.00 ± 1.27, p = 0.002; (2.62 ± 2.08 vs. (0.62 ± 0.29, p < 0.01, respectively]. In RA patients, the percentage of AhR positive cells in CD4+CD25+T cells was significantly lower than that from controls [17.90 (6.10 ± 80.10% vs. (52.49 ± 19.18%, p < 0.01]; In healthy controls, the percentage of AhR positive cells in CD4+CD25+T cells was significantly higher than that in CCR6+CD4+T cells, and was also significantly higher than that in PBMCs [(52.49 ± 19.18% vs. (23.18 ± 5.62% vs. (18.06 ± 7.80%, X 2 = 24.03, p < 0.01]; in RA patients, the percentage of AhR positive cells in CCR6+CD4+T cells was significantly increased than that in CD4+CD25+T cells and PBMCs [(46.02 ± 14.68% vs. 17.90 (6.10 ± 80.10% vs. (34.22 ± 10.33%, X 2 = 38.29, p < 0.01]; Nevertheless, no statistically significant relationship was found between clinical data and AhR positive cells in CCR6+CD4+T and CD4+CD25+T cells. Conclusion: AhR may participate in the pathological progress of RA by controlling the differentiation of Th17 and Treg cells in peripheral blood.

  12. Unbalanced expression of aryl hydrocarbon receptor in peripheral blood CCR6+CD4+and CD4+CD25+T cells of rheumatoid arthritis.

    Science.gov (United States)

    Cheng, Lin; Qian, Long; Tan, Yue; Wang, Guo-Sheng; Li, Xiao-Mei; Li, Xiang-Pei; Luo, Chao-Yin

    The goal of this study was to analyze the role of aryl hydrocarbon receptor in peripheral blood CCR6 + CD4 + and CD4 + CD25 + T cells of patients with rheumatoid arthritis. Flow cytometry was applied to determine the proportion of AhR positive cells in CCR6 + CD4 + T, CD4 + CD25 + T and peripheral blood peripheral mononuclear cells from each subject. AhR mRNA and CYP1A1 mRNA relative expression levels were tested by real-time PCR. The percentage of AhR positive cells in peripheral blood mononuclear cells was higher in RA group than that in healthy cases [(35.23±10.71)% vs. (18.83±7.32)%, p<0.01]. The expression levels of AhR and CYP1A1 were both increased in patients with RA while compared to controls [(3.71±1.63) vs. (2.00±1.27), p=0.002; (2.62±2.08) vs. (0.62±0.29), p<0.01, respectively]. In RA patients, the percentage of AhR positive cells in CD4 + CD25 + T cells was significantly lower than that from controls [17.90 (6.10±80.10)% vs. (52.49±19.18)%, p<0.01]; In healthy controls, the percentage of AhR positive cells in CD4 + CD25 + T cells was significantly higher than that in CCR6 + CD4 + T cells, and was also significantly higher than that in PBMCs [(52.49±19.18)% vs. (23.18±5.62)% vs. (18.06±7.80)%, X 2 =24.03, p<0.01]; in RA patients, the percentage of AhR positive cells in CCR6 + CD4 + T cells was significantly increased than that in CD4 + CD25 + T cells and PBMCs [(46.02±14.68)% vs. 17.90 (6.10±80.10)% vs. (34.22±10.33)%, X 2 =38.29, p<0.01]; Nevertheless, no statistically significant relationship was found between clinical data and AhR positive cells in CCR6 + CD4 + T and CD4 + CD25 + T cells. AhR may participate in the pathological progress of RA by controlling the differentiation of Th17 and Treg cells in peripheral blood. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

  13. TRIGGER

    CERN Multimedia

    W. Smith

    2011-01-01

    Level-1 Trigger Hardware and Software Overall the L1 trigger hardware has been running very smoothly during the last months of proton running. Modifications for the heavy-ion run have been made where necessary. The maximal design rate of 100 kHz can be sustained without problems. All L1 latencies have been rechecked. The recently installed Forward Scintillating Counters (FSC) are being used in the heavy ion run. The ZDC scintillators have been dismantled, but the calorimeter itself remains. We now send the L1 accept signal and other control signals to TOTEM. Trigger cables from TOTEM to CMS will be installed during the Christmas shutdown, so that the TOTEM data can be fully integrated within the CMS readout. New beam gas triggers have been developed, since the BSC-based trigger is no longer usable at high luminosities. In particular, a special BPTX signal is used after a quiet period with no collisions. There is an ongoing campaign to provide enough spare modules for the different subsystems. For example...

  14. TRIGGER

    CERN Multimedia

    J. Alimena

    2013-01-01

    Trigger Strategy Group The Strategy for Trigger Evolution And Monitoring (STEAM) group is responsible for the development of future High-Level Trigger menus, as well as of its DQM and validation, in collaboration and with the technical support of the PdmV group. Taking into account the beam energy and luminosity expected in 2015, a rough estimate of the trigger rates indicates a factor four increase with respect to 2012 conditions. Assuming that a factor two can be tolerated thanks to the increase in offline storage and processing capabilities, a toy menu has been developed using the new OpenHLT workflow to estimate the transverse energy/momentum thresholds that would halve the current trigger rates. The CPU time needed to run the HLT has been compared between data taken with 25 ns and 50 ns bunch spacing, for equivalent pile-up: no significant difference was observed on the global time per event distribution at the only available data point, corresponding to a pile-up of about 10 interactions. Using th...

  15. TRIGGER

    CERN Multimedia

    by Wesley Smith

    2011-01-01

    Level-1 Trigger Hardware and Software After the winter shutdown minor hardware problems in several subsystems appeared and were corrected. A reassessment of the overall latency has been made. In the TTC system shorter cables between TTCci and TTCex have been installed, which saved one bunch crossing, but which may have required an adjustment of the RPC timing. In order to tackle Pixel out-of-syncs without influencing other subsystems, a special hardware/firmware re-sync protocol has been introduced in the Global Trigger. The link between the Global Calorimeter Trigger and the Global Trigger with the new optical Global Trigger Interface and optical receiver daughterboards has been successfully tested in the Electronics Integration Centre in building 904. New firmware in the GCT now allows a setting to remove the HF towers from energy sums. The HF sleeves have been replaced, which should lead to reduced rates of anomalous signals, which may allow their inclusion after this is validated. For ECAL, improvements i...

  16. TRIGGER

    CERN Multimedia

    W. Smith

    Level-1 Trigger Hardware The CERN group is working on the TTC system. Seven out of nine sub-detector TTC VME crates with all fibers cabled are installed in USC55. 17 Local Trigger Controller (LTC) boards have been received from production and are in the process of being tested. The RF2TTC module replacing the TTCmi machine interface has been delivered and will replace the TTCci module used to mimic the LHC clock. 11 out of 12 crates housing the barrel ECAL off-detector electronics have been installed in USC55 after commissioning at the Electronics Integration Centre in building 904. The cabling to the Regional Calorimeter Trigger (RCT) is terminated. The Lisbon group has completed the Synchronization and Link mezzanine board (SLB) production. The Palaiseau group has fully tested and installed 33 out of 40 Trigger Concentrator Cards (TCC). The seven remaining boards are being remade. The barrel TCC boards have been tested at the H4 test beam, and good agreement with emulator predictions were found. The cons...

  17. 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

  18. Hexachlorobenzene modulates the crosstalk between the aryl hydrocarbon receptor and transforming growth factor-β1 signaling, enhancing human breast cancer cell migration and invasion

    International Nuclear Information System (INIS)

    Miret, Noelia; Pontillo, Carolina; Ventura, Clara; Carozzo, Alejandro; Chiappini, Florencia

    2016-01-01

    Highlights: • HCB enhances TGF-β1 expression and activation levels in breast cancer cells. • HCB activates TGF-β1 pathways: Smad3, JNK and p38. • The HCB- induced migration and invasion involves TGF-β1 signaling pathways. • HCB modulates AhR levels and activation. • HCB enhances TGF-β1 mRNA expression in an AhR-dependent manner. - Abstract: Given the number of women affected by breast cancer, considerable interest has been raised in understanding the relationships between environmental chemicals and disease onset. Hexachlorobenzene (HCB) is a dioxin-like compound that is widely distributed in the environment and is a weak ligand of the aryl hydrocarbon receptor (AhR). We previously demonstrated that HCB acts as an endocrine disruptor capable of stimulating cell proliferation, migration, invasion, and metastasis in different breast cancer models. In addition, increasing evidence indicates that transforming growth factor-β1 (TGF-β1) can contribute to tumor maintenance and progression. In this context, this work investigated the effect of HCB (0.005, 0.05, 0.5, and 5 μM) on TGF-β1 signaling and AhR/TGF-β1 crosstalk in the human breast cancer cell line MDA-MB-231 and analyzed whether TGF-β1 pathways are involved in HCB-induced cell migration and invasion. RT-qPCR results indicated that HCB reduces AhR mRNA expression through TGF-β1 signaling but enhances TGF-β1 mRNA levels involving AhR signaling. Western blot analysis demonstrated that HCB could increase TGF-β1 protein levels and activation, as well as Smad3, JNK, and p38 phosphorylation. In addition, low and high doses of HCB were determined to exert differential effects on AhR protein levels, localization, and activation, with a high dose (5 μM) inducing AhR nuclear translocation and AhR-dependent CYP1A1 expression. These findings also revealed that c-Src and AhR are involved in HCB-mediated activation of Smad3. HCB enhances cell migration (scratch motility assay) and invasion (Transwell

  19. Role of the aryl hydrocarbon receptor and Cyp1b1 in the antiestrogenic activity of 2,3,7,8-tetrachlorodibenzo-p-dioxin

    Energy Technology Data Exchange (ETDEWEB)

    Takemoto, Kei; Nakajima, Miki; Fujiki, Yuto; Katoh, Miki; Yokoi, Tsuyoshi [Division of Drug Metabolism, Faculty of Pharmaceutical Sciences, Kanazawa University, Takara-machi 13-1, 920-0934, Kanazawa (Japan); Gonzalez, Frank J. [National Cancer Institute, MD 20892, Bethesda (United States)

    2004-06-01

    The role of aryl hydrocarbon receptor (AhR) and cytochrome P450 (Cyp) 1 family in the antiestrogenic activity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was investigated in vivo. Immature (21 days old) AhR, Cyp1a2, or Cyp1b1 knockout (-/-) mice were treated intraperitoneally with estradiol (E2, 20 ng/mouse per day, for 14 consecutive days) and/or TCDD (200 ng/mouse per day, on days 7, 9, 11, and 13). Uterine wet weight and uterine peroxidase activity (UPA) were measured as markers of estrogen responsiveness. UPA was a better marker of estrogen responsiveness than the uterine wet weight. In AhR wild-type (+/+) mice, UPA (208.1{+-}81.6 units/g tissue) was increased by the administration of E2 (to 297.2{+-}178.7 units/g). The administration of TCDD significantly (p<0.01) decreased the UPA (10.5{+-}3.4 units/g) compared with that in the control mice. Co-administration of TCDD with E2 also significantly (p<0.05) decreased the UPA (18.8{+-}19.9 units/g) compared with that in E2-treated mice. In AhR(-/-) mice, UPA (162.9{+-}146.7 units/g) was significantly (p<0.01) increased by the administration of E2 (486.8{+-}108.2 units/g). In contrast to the results in AhR(+/+) mice, UPA was not affected by the administration of TCDD (51.8{+-}70.6 units/g) compared with control, and co-administration of TCDD with E2 (545.8{+-}189.4 units/g) compared with that in E2-treated mice. In Cyp1a2/1b1(+/+) mice, UPA was significantly (p<0.05) increased by the administration of E2 (70.0{+-}36.4 units/g). Co-administration of TCDD with E2 significantly (p<0.05) decreased the UPA (29.6{+-}22.2 units/g) compared with that in E2-treated mice. In Cyp1a2(-/-) mice, co-administration of TCDD with E2 significantly (p<0.01) decreased the UPA (6.8{+-}5.1 units/g) compared with that in E2-treated mice. In Cyp1b1(-/-) mice, UPA (5.5{+-}8.1 units/g) was significantly (p<0.05) increased by the administration of E2 (56.6{+-}34.1 units/g). In contrast to the results in Cyp1a2/1b1(+/+) mice or Cyp1a2

  20. Aryl hydrocarbon receptor/cytochrome P450 1A1 pathway mediates breast cancer stem cells expansion through PTEN inhibition and β-Catenin and Akt activation.

    Science.gov (United States)

    Al-Dhfyan, Abdullah; Alhoshani, Ali; Korashy, Hesham M

    2017-01-19

    Breast cancer stem cells (CSCs) are small sub-type of the whole cancer cells that drive tumor initiation, progression and metastasis. Recent studies have demonstrated a role for the aryl hydrocarbon receptor (AhR)/cytochrome P4501A1 pathway in CSCs expansion. However, the exact molecular mechanisms remain unclear. The current study was designed to a) determine the effect of AhR activation and inhibition on breast CSCs development, maintenance, self-renewal, and chemoresistance at the in vitro and in vivo levels and b) explore the role of β-Catenin, PI3K/Akt, and PTEN signaling pathways. To test this hypothesis, CSC characteristics of five human breast cancer cells; SKBR-3, MCF-7, and MDA-MB231, HS587T, and T47D treated with AhR activators or inhibitor were determined using Aldefluor assay, side population, and mammosphere formation. The mRNA, protein expression, cellular content and localization of the target genes were determined by RT-PCR, Western blot analysis, and Immunofluorescence, respectively. At the in vivo level, female Balb/c mice were treated with AhR/CYP1A1 inducer and histopathology changes and Immunohistochemistry examination for target proteins were determined. The constitutive mRNA expression and cellular content of CYP1A1 and CYP1B1, AhR-regulated genes, were markedly higher in CSCs more than differentiating non-CSCs of five different human breast cancer cells. Activation of AhR/CYP1A1 in MCF-7 cells by TCDD and DMBA, strong AhR activators, significantly increased CSC-specific markers, mammosphere formation, aldehyde dehydrogenase (ALDH) activity, and percentage of side population (SP) cells, whereas inactivation of AhR/CYP1A1 using chemical inhibitor, α-naphthoflavone (α-NF), or by genetic shRNA knockdown, significantly inhibited the upregulation of ALDH activity and SP cells. Importantly, inactivation of the AhR/CYP1A1 significantly increased sensitization of CSCs to the chemotherapeutic agent doxorubicin. Mechanistically, Induction of Ah

  1. 2,3,7,8-Tetrachlorodibenzo-p-dioxin poly(ADP-ribose) polymerase (TiPARP, ARTD14) is a mono-ADP-ribosyltransferase and repressor of aryl hydrocarbon receptor transactivation.

    Science.gov (United States)

    MacPherson, Laura; Tamblyn, Laura; Rajendra, Sharanya; Bralha, Fernando; McPherson, J Peter; Matthews, Jason

    2013-02-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-inducible poly(ADP-ribose) polymerase (TiPARP/ARTD14) is a member of the PARP family and is regulated by the aryl hydrocarbon receptor (AHR); however, little is known about TiPARP function. In this study, we examined the catalytic function of TiPARP and determined its role in AHR transactivation. We observed that TiPARP exhibited auto-mono-ADP-ribosyltransferase activity and ribosylated core histones. RNAi-mediated knockdown of TiPARP in T-47D breast cancer and HuH-7 hepatoma cells increased TCDD-dependent cytochrome P450 1A1 (CYP1A1) and CYP1B1 messenger RNA (mRNA) expression levels and recruitment of AHR to both genes. Overexpression of TiPARP reduced AHR-dependent increases in CYP1A1-reporter gene activity, which was restored by overexpression of AHR, but not aryl hydrocarbon receptor nuclear translocator. Deletion and mutagenesis studies showed that TiPARP-mediated inhibition of AHR required the zinc-finger and catalytic domains. TiPARP and AHR co-localized in the nucleus, directly interacted and both were recruited to CYP1A1 in response to TCDD. Overexpression of Tiparp enhanced, whereas RNAi-mediated knockdown of TiPARP reduced TCDD-dependent AHR proteolytic degradation. TCDD-dependent induction of AHR target genes was enhanced in Tiparp(-/-) mouse embryonic fibroblasts compared with wildtype controls. Our findings show that TiPARP is a mono-ADP-ribosyltransferase and a transcriptional repressor of AHR, revealing a novel negative feedback loop in AHR signalling.

  2. Induction of hepatic carbonyl reductase/20{beta}-hydroxysteroid dehydrogenase mRNA in rainbow trout downstream from sewage treatment works-Possible roles of aryl hydrocarbon receptor agonists and oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Albertsson, E., E-mail: eva.albertsson@zool.gu.se [Department of Zoology, University of Gothenburg, Box 463, SE-405 30 Goeteborg (Sweden); Larsson, D.G.J. [Department of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Box 434, SE-405 30 Goeteborg (Sweden); Foerlin, L. [Department of Zoology, University of Gothenburg, Box 463, SE-405 30 Goeteborg (Sweden)

    2010-05-05

    Carbonyl reductase/20{beta}-hydroxysteroid dehydrogenase (CR/20{beta}-HSD) serves both as a key enzyme in the gonadal synthesis of maturing-inducing hormone in salmonids, and as an enzyme protecting against certain reactive oxygen species. We have previously shown that mRNA of the hepatic CR/20{beta}-HSD B isoform is increased in rainbow trout caged downstream from a Swedish sewage treatment plant. Here, we report an increase of both the A as well as B form in fish kept downstream from a second sewage treatment plant. The two mRNAs were also induced in fish hepatoma cells in vitro after exposure to effluent extract. This indicates that the effects observed in vivo could be a direct effect on the liver, i.e. the mRNA induction does not require a signal from any other organ. When fish were exposed in vivo to several effluents treated with more advanced methods (ozone, moving bed biofilm reactor or membrane bioreactor) the expression of hepatic mRNA CR/20{beta}-HSD A and B was significantly reduced. Their abundance did not parallel the reduction of estrogen-responsive transcripts, in agreement with our previous observations that ethinylestradiol is not a potent inducer. Treatment with norethisterone, methyltestosterone or hydrocortisone in vivo did not induce the hepatic CR/20{beta}-HSD A and B mRNA expression. In contrast, both isoforms were markedly induced by the aryl hydrocarbon receptor agonist {beta}-naphthoflavone as well as by the pro-oxidant herbicide paraquat. We hypothesize that the induction of CR/20{beta}-HSD A and B by sewage effluents could be due to anthropogenic contaminants stimulating the aryl hydrocarbon receptor and/or causing oxidative stress.

  3. Induction of hepatic carbonyl reductase/20β-hydroxysteroid dehydrogenase mRNA in rainbow trout downstream from sewage treatment works-Possible roles of aryl hydrocarbon receptor agonists and oxidative stress

    International Nuclear Information System (INIS)

    Albertsson, E.; Larsson, D.G.J.; Foerlin, L.

    2010-01-01

    Carbonyl reductase/20β-hydroxysteroid dehydrogenase (CR/20β-HSD) serves both as a key enzyme in the gonadal synthesis of maturing-inducing hormone in salmonids, and as an enzyme protecting against certain reactive oxygen species. We have previously shown that mRNA of the hepatic CR/20β-HSD B isoform is increased in rainbow trout caged downstream from a Swedish sewage treatment plant. Here, we report an increase of both the A as well as B form in fish kept downstream from a second sewage treatment plant. The two mRNAs were also induced in fish hepatoma cells in vitro after exposure to effluent extract. This indicates that the effects observed in vivo could be a direct effect on the liver, i.e. the mRNA induction does not require a signal from any other organ. When fish were exposed in vivo to several effluents treated with more advanced methods (ozone, moving bed biofilm reactor or membrane bioreactor) the expression of hepatic mRNA CR/20β-HSD A and B was significantly reduced. Their abundance did not parallel the reduction of estrogen-responsive transcripts, in agreement with our previous observations that ethinylestradiol is not a potent inducer. Treatment with norethisterone, methyltestosterone or hydrocortisone in vivo did not induce the hepatic CR/20β-HSD A and B mRNA expression. In contrast, both isoforms were markedly induced by the aryl hydrocarbon receptor agonist β-naphthoflavone as well as by the pro-oxidant herbicide paraquat. We hypothesize that the induction of CR/20β-HSD A and B by sewage effluents could be due to anthropogenic contaminants stimulating the aryl hydrocarbon receptor and/or causing oxidative stress.

  4. Effects of Developmental Activation of the Aryl Hydrocarbon Receptor by 2,3,7,8-Tetrachlorodibenzo-p-dioxin on Long-term Self-renewal of Murine Hematopoietic Stem Cells.

    Science.gov (United States)

    Laiosa, Michael D; Tate, Everett R; Ahrenhoerster, Lori S; Chen, Yuhong; Wang, Demin

    2016-07-01

    Human epidemiological and animal studies suggest that developmental exposure to contaminants that activate the aryl hydrocarbon receptor (AHR) lead to suppression of immune system function throughout life. The persistence of immune deficiency throughout life suggests that the cellular target of AHR activation is a fetal hematopoietic progenitor or stem cell. The aim of this study was to identify the effects of transplacental exposure to an AHR agonist on long-term self-renewal of fetal hematopoietic stem cells. Pregnant C57BL/6 or AHR+/- mice were exposed to the AHR agonist, 2,3,7,8-tetra-​chlorodibenzo-p-dioxin (TCDD). On day 14 of gestation, hematopoietic progenitors from wild-type or AHR-deficient fetuses were placed into in vitro T-lymphocyte differentiation cultures to identify the effects of transplacental TCDD on AHR activation in the fetus. We next analyzed the fetal hematopoietic progenitor cells for changes in reactive oxygen species (ROS). Finally, hematopoietic progenitors from fetuses exposed transplacentally to TCDD were mixed 1:1 with cells from congenic controls and used to reconstitute lethally irradiated recipients for analysis of long-term self-renewal potential. Our findings suggested that the effects of TCDD on the developing hematopoietic system were mediated by direct AHR activation in the fetus. Furthermore, developmental AHR activation by TCDD increased ROS in the fetal hematopoietic stem cells, and the elevated ROS was associated with a reduced capacity of the TCDD-exposed fetal cells to compete with control cells in a mixed competitive irradiation/reconstitution assay. Our findings indicate that AHR activation by TCDD in the fetus during pregnancy leads to impairment of long-term self-renewal of hematopoietic stem cells. Laiosa MD, Tate ER, Ahrenhoerster LS, Chen Y, Wang D. 2016. Effects of developmental activation of the aryl hydrocarbon receptor by 2,3,7,8-tetrachlorodibenzo-p-dioxin on long-term self-renewal of murine hematopoietic

  5. Dioxin-induced retardation of development through a reduction in the expression of pituitary hormones and possible involvement of an aryl hydrocarbon receptor in this defect: A comparative study using two strains of mice with different sensitivities to dioxin

    Energy Technology Data Exchange (ETDEWEB)

    Takeda, Tomoki; Taura, Junki; Hattori, Yukiko; Ishii, Yuji; Yamada, Hideyuki, E-mail: hyamada@phar.kyushu-u.ac.jp

    2014-08-01

    We have previously revealed that treating pregnant rats with 2,3,7,8-tetracholorodibenzo-p-dioxin (TCDD) reduces the expression of gonadotropins and growth hormone (GH) in the fetal and neonatal pituitary. A change in gonadotropin expression impairs the testicular expression of steroidogenic proteins in perinatal pups, and imprint defects in sexual behavior after reaching maturity. In this study, we examined whether TCDD also affects the expression of gonadotropin and GH in mice using C57BL/6J and DBA/2J strains which express the aryl hydrocarbon receptor (Ahr) exhibiting a different affinity for TCDD. When pregnant C57BL/6J mice at gestational day (GD) 12 were given oral TCDD (0.2–20 μg/kg), all doses significantly attenuated the pituitary expression of gonadotropin mRNAs in fetuses at GD18. On the other hand, in DBA/2J mice, a much higher dose of TCDD (20 μg/kg) was needed to produce a significant attenuation. Such reduction in the C57BL/6J strain continued until at least postnatal day (PND) 4. In agreement with this, TCDD reduced the testicular expression of steroidogenic proteins in C57BL/6J neonates at PND2 and 4, although the same did not occur in the fetal testis and ovary. Furthermore, TCDD reduced the perinatal expression of GH, litter size and the body weight of newborn pups only in the C57BL/6J strain. These results suggest that 1) also in mice, maternal exposure to TCDD attenuates gonadotropin-regulated steroidogenesis and GH expression leading to the impairment of pup development and sexual immaturity; and 2) Ahr activation during the late fetal and early postnatal stages is required for these defects. - Highlights: • The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on mouse growth was studied. • TCDD reduced the levels of luteinizing hormone and growth hormone in perinatal pups. • Maternal exposure to TCDD also attenuated testicular steroidogenesis in pups. • The above effects of TCDD were more pronounced in C57BL/6J than in DBA/2J

  6. Dioxin-induced retardation of development through a reduction in the expression of pituitary hormones and possible involvement of an aryl hydrocarbon receptor in this defect: A comparative study using two strains of mice with different sensitivities to dioxin

    International Nuclear Information System (INIS)

    Takeda, Tomoki; Taura, Junki; Hattori, Yukiko; Ishii, Yuji; Yamada, Hideyuki

    2014-01-01

    We have previously revealed that treating pregnant rats with 2,3,7,8-tetracholorodibenzo-p-dioxin (TCDD) reduces the expression of gonadotropins and growth hormone (GH) in the fetal and neonatal pituitary. A change in gonadotropin expression impairs the testicular expression of steroidogenic proteins in perinatal pups, and imprint defects in sexual behavior after reaching maturity. In this study, we examined whether TCDD also affects the expression of gonadotropin and GH in mice using C57BL/6J and DBA/2J strains which express the aryl hydrocarbon receptor (Ahr) exhibiting a different affinity for TCDD. When pregnant C57BL/6J mice at gestational day (GD) 12 were given oral TCDD (0.2–20 μg/kg), all doses significantly attenuated the pituitary expression of gonadotropin mRNAs in fetuses at GD18. On the other hand, in DBA/2J mice, a much higher dose of TCDD (20 μg/kg) was needed to produce a significant attenuation. Such reduction in the C57BL/6J strain continued until at least postnatal day (PND) 4. In agreement with this, TCDD reduced the testicular expression of steroidogenic proteins in C57BL/6J neonates at PND2 and 4, although the same did not occur in the fetal testis and ovary. Furthermore, TCDD reduced the perinatal expression of GH, litter size and the body weight of newborn pups only in the C57BL/6J strain. These results suggest that 1) also in mice, maternal exposure to TCDD attenuates gonadotropin-regulated steroidogenesis and GH expression leading to the impairment of pup development and sexual immaturity; and 2) Ahr activation during the late fetal and early postnatal stages is required for these defects. - Highlights: • The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on mouse growth was studied. • TCDD reduced the levels of luteinizing hormone and growth hormone in perinatal pups. • Maternal exposure to TCDD also attenuated testicular steroidogenesis in pups. • The above effects of TCDD were more pronounced in C57BL/6J than in DBA/2J

  7. Assays of dioxins and dioxin-like compounds in actually contaminated soils using transgenic tobacco plants carrying a recombinant mouse aryl hydrocarbon receptor-mediated β-glucuronidase reporter gene expression system

    Science.gov (United States)

    Inui, Hideyuki; Gion, Keiko; Utani, Yasushi; Wakai, Taketo; Kodama, Susumu; Eun, Heesoo; Kim, Yun-Seok; Ohkawa, Hideo

    2012-01-01

    The transgenic tobacco plant XD4V-26 carrying the recombinant mouse aryl hydrocarbon receptor XD4V-mediated β-glucuronidase (GUS) reporter gene expression system was used for assay of dioxins and dioxin-like compounds consisting of polychlorodibenzo-p-dioxins, polychlorinated dibenzofurans, and coplanar polychlorinated biphenyls (Co-PCBs) in actually contaminated soils. The transgenic tobacco plant XD4V-26 showed a significant dose-dependent induced GUS activity when cultured on MS medium containing PCB126 [toxic equivalency factor (TEF) = 0.1]. In contrast, PCB169 and PCB180, which have 0.03 of TEF and unassigned TEF values, respectively, did not significantly induce GUS activity under the same conditions as with PCB126. When the tobacco plants were cultivated for up to 5 weeks on actually contaminated soils with dioxins and dioxin-like compounds collected from the periphery of an incinerator used for disposal of life and industrial wastes, GUS activity in the leaves was dose-dependently increased. The plants clearly detected 360 pg-TEQ g−1 of dioxins and dioxin-like compounds in this assay. There was a positive correlation between GUS activity and TEQ value of dioxins and dioxin-like compounds in the plants. This assay does not require any extraction and purification processes for the actually contaminated soil samples. PMID:22428884

  8. Two likely targets for the anti-cancer effect of indole derivatives from cruciferous vegetables: PI3K/Akt/mTOR signalling pathway and the aryl hydrocarbon receptor.

    Science.gov (United States)

    Popolo, Ada; Pinto, Aldo; Daglia, Maria; Nabavi, Seyed Fazel; Farooqi, Ammad Ahmad; Rastrelli, Luca

    2017-10-01

    Diets containing high quantities of plant foods are linked with a decreased likelihood of incidence of cancer. Several common plant-based dietary components exert effects on DNA methylation levels, and can positively influence genome stability and the transcription of tumor suppressors and oncogenes. Indole-3-carbinol (I3C) is a substance present in vegetables of the Brassicaeae family, especially broccoli, white cabbage, Brussels sprouts and cauliflower. The in vivo biological effects of I3C are ascribed to a series of oligomeric products (including 3,3'-diindolylmethane), developed under acidic conditions. I3C is one of the many natural products and bioactive compounds found in foods which have recently received much attention for its potential effects in cancer prevention and treatment. In vitro studies report that I3C suppresses the proliferation of different tumor cells, including those isolated from breast, prostate, endometrium, and colon cancers. I3C resulted to be a potent in vivo chemopreventive agent for certain hormone-dependent cancers, including breast and cervical cancer. However, the mechanisms underlying these effects are not well defined. In this review, we have analysed recent literature on the use of indole derivatives against various forms of cancer, and have identified the main signalling pathways involved in their anti-cancer effect as PI3K/Akt/mTOR and the aryl hydrocarbon receptor. Copyright © 2017. Published by Elsevier Ltd.

  9. Assays of dioxins and dioxin-like compounds in actually contaminated soils using transgenic tobacco plants carrying a recombinant mouse aryl hydrocarbon receptor-mediated β-glucuronidase reporter gene expression system.

    Science.gov (United States)

    Inui, Hideyuki; Gion, Keiko; Utani, Yasushi; Wakai, Taketo; Kodama, Susumu; Eun, Heesoo; Kim, Yun-Seok; Ohkawa, Hideo

    2012-01-01

    The transgenic tobacco plant XD4V-26 carrying the recombinant mouse aryl hydrocarbon receptor XD4V-mediated β-glucuronidase (GUS) reporter gene expression system was used for assay of dioxins and dioxin-like compounds consisting of polychlorinated dibenzeno-p-dioxins, polychlorinated dibenzofurans, and coplanar polychlorinated biphenyls (Co-PCBs) in actually contaminated soils. The transgenic tobacco plant XD4V-26 showed a significant dose-dependent induced GUS activity when cultured on MS medium containing PCB126 [toxic equivalency factor (TEF) = 0.1]. In contrast, PCB169 and PCB180, which have 0.03 of TEF and unassigned TEF values, respectively, did not significantly induce GUS activity under the same conditions as with PCB126. When the tobacco plants were cultivated for up to 5 weeks on actually contaminated soils with dioxins and dioxin-like compounds collected from the periphery of an incinerator used for disposal of residential and industrial wastes, GUS activity in the leaves was dose-dependently increased. The plants clearly detected 360 pg-TEQ g(-1) of dioxins and dioxin-like compounds in this assay. There was a positive correlation between GUS activity and TEQ value of dioxins and dioxin-like compounds in the plants. This assay does not require any extraction and purification processes for the actually contaminated soil samples.

  10. Aryl hydrocarbon receptor-mediated disruption of contact inhibition is associated with connexin43 downregulation and inhibition of gap junctional intercellular communication

    Czech Academy of Sciences Publication Activity Database

    Andrysík, Zdeněk (ed.); Procházková, Jiřina; Kabátková, Markéta; Umannová, Lenka; Šimečková, P.; Kohoutek, J.; Machala, M.; Vondráček, Jan

    2013-01-01

    Roč. 87, č. 3 (2013), s. 491-503 ISSN 0340-5761 R&D Projects: GA ČR(CZ) GA524/09/1337 Institutional research plan: CEZ:AV0Z50040702 Institutional support: RVO:68081707 Keywords : POLYCYCLIC AROMATIC-HYDROCARBONS * LIVER EPITHELIAL-CELLS * RAT-LIVER * GENE-EXPRESSION Subject RIV: BO - Biophysics Impact factor: 5.078, year: 2013

  11. The inhibition effect of 2,3,7,8-tetrachlorinated dibenzo-p-dioxin-induced aryl hydrocarbon receptor activation in human hepatoma cells with the treatment of cadmium chloride

    Energy Technology Data Exchange (ETDEWEB)

    Chao, How-Ran [Department of Environmental Science and Engineering, National Pingtung University of Science and Technology, Neipu, Pingtung 912, Taiwan (China); Emerging Compounds Research Center, National Pingtung University of Science and Technology, Neipu, Pingtung 912, Taiwan (China); Tsou, Tsui-Chun [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Miaoli 350, Taiwan (China); Chen, Hung-Ta [Sustainable Environment Research Center, National Cheng Kung University, Tainan 701, Taiwan (China); Chang, Eddy Essen; Tsai, Feng-Yuan [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Miaoli 350, Taiwan (China); Lin, Ding-Yan [Department of Environmental Science and Engineering, National Pingtung University of Science and Technology, Neipu, Pingtung 912, Taiwan (China); Chen, Fu-An [Graduate Institute of Pharmaceutical Science, Department of Pharmacy, Tajen University, Yan-Pu, Pingtung 907, Taiwan (China); Wang, Ya-Fen, E-mail: yfwang@cycu.edu.tw [Department of Bioenvironmental Engineering, Chung Yuan Christian University, Chungli, Taoyuan 320, Taiwan (China); R and D Center of Membrane Technology, Chung Yuan Christian University, Chungli 320, Taiwan (China)

    2009-10-15

    Polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), considered as endocrine disruptors, tend to accumulate in fatty tissues. Dioxin-responsive element chemical activated luciferase gene expression assay (DRE-luciferase assay) has been recognized as a semi-quantitative method for screening dioxins for its fast and low-cost as compared with HRGC/HRMS. However, some problems with the bioassay, including specificity, detection variation resulted from different cleanup strategies, and uncertainty of false-negative or false-positive results, remain to be overcome. Cadmium is a prevalent environmental contaminant around the world. This study was aimed to examine the effects of cadmium on the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced activation of aryl hydrocarbon receptor (AhR)-mediated gene expression in human hepatoma cells (Huh7-DRE-Luc cells and Huh7 cells). Ethoxyresorufin-O-deethylase (EROD) and DRE-luciferase assay were employed to determine the enzyme activity of cytochrome P450 1A1 (CYP1A1) and activation of AhR, respectively. The results showed that Cd{sup 2+} levels significantly inhibited the induction of TCDD-induced CYP1A1 and DRE luciferase activation in hepatoma cells. The 50% inhibited concentrations (IC{sub 50}) of CdCl{sub 2} were 0.414 {mu}M (95% confidence interval (C.I.): 0.230-0.602 {mu}M) in Huh7-DRE-Luc cells and 23.2 {mu}M (95% C.I.: 21.7-25.4 {mu}M) in Huh7 cells. Accordingly, prevention of interference with non-dioxin-like compounds in a DRE-luciferase assay is of great importance in an extensive cleanup procedure.

  12. Effect of PCB 126 on aryl hydrocarbon receptor 1 (AHR1) and AHR1 nuclear translocator 1 (ARNT1) mRNA expression and CYP1 monooxygenase activity in chicken (Gallus domesticus) ovarian follicles.

    Science.gov (United States)

    Wójcik, Dagmara; Antos, Piotr A; Katarzyńska, Dorota; Hrabia, Anna; Sechman, Andrzej

    2015-12-03

    The aim of the experiment was to study the in vitro effect of 3,3',4,4',5-pentachlorobiphenyl (PCB 126; a coplanar PCB congener) on aryl hydrocarbon receptor (AHR1) and AHR1 nuclear translocator (ARNT1) mRNA expression and the activity of CYP1 family monooxygenases in chicken ovarian follicles. White (1-4 mm) and yellowish (4-8 mm) prehierarchical follicles as well as fragments of the theca and granulosa layers of the 3 largest preovulatory follicles (F3-F1) were incubated in a medium supplemented with 0 (control group), 1, 10 or 100 nM PCB 126. The incubation was carried out for 6 h or 24 h for determination of mRNA expression of AHR1 and ARNT1 genes (real-time qPCR) and CYP1 monooxygenase activity (EROD and MROD fluorometric assays), respectively. It was found that chicken ovarian follicles express mRNA of AHR1 and ARNT1 genes. A modulatory effect of PCB 126 on AHR1 and ARNT1 expression depended not only on the biphenyl concentration but also on the follicular layer and the maturational state of the follicle. EROD and MROD activities appeared predominantly in the granulosa layer of the yellow preovulatory follicles. PCB 126 induced these activities in a dose-dependent manner in all ovarian follicles. The obtained results suggest that ovarian follicles, especially the granulosa layer, are involved in the detoxification process of PCBs in the laying hen. Taking this finding into consideration it can be suggested that the granulosa layer of the yellow hierarchical follicles plays a key role in the protective mechanism which reduces the amount of transferred dioxin-like compounds into the yolk of the oocyte. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. Estrogen receptor α and aryl hydrocarbon receptor cross-talk in a transfected hepatoma cell line (HepG2 exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin

    Directory of Open Access Journals (Sweden)

    Manuela Göttel

    2014-01-01

    Full Text Available The prototype dioxin congener 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD is known to exert anti-estrogenic effects via activation of the aryl hydrocarbon receptor (AhR by interfering with the regulation of oestrogen homeostasis and the estrogen receptor α (ERα signalling pathway. The AhR/ER cross-talk is considered to play a crucial role in TCDD- and E2-dependent mechanisms of carcinogenesis, though the concerted mechanism of action in the liver is not yet elucidated. The present study investigated TCDD's impact on the transcriptional cross-talk between AhR and ERα and its modulation by 17β-estradiol (E2 in the human hepatoma cell line HepG2, which is AhR-responsive but ERα-negative. Transient transfection assays with co-transfection of hERα and supplementation of receptor antagonists showed anti-estrogenic action of TCDD via down-regulation of E2-induced ERα signaling. In contrast, enhancement of AhR signaling dependent on ERα was observed providing evidence for increased cytochrome P450 (CYP induction to promote E2 metabolism. However, relative mRNA levels of major E2-metabolizing CYP1A1 and 1B1 and the main E2-detoxifying catechol-O-methyltransferase were not affected by the co-treatments. This study provides new evidence of a TCDD-activated AhR-mediated molecular AhR/ERα cross-talk mechanism at transcriptional level via indirect inhibition of ERα and enhanced transcriptional activity of AhR in HepG2 cells.

  14. 2,3,7,8-Tetrachlorodibenzo-p-dioxin activates the aryl hydrocarbon receptor and alters sex steroid hormone secretion without affecting growth of mouse antral follicles in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Karman, Bethany N., E-mail: bklement@illinois.edu; Basavarajappa, Mallikarjuna S., E-mail: mbshivapur@gmail.com; Craig, Zelieann R., E-mail: zelieann@illinois.edu; Flaws, Jodi A., E-mail: jflaws@illinois.edu

    2012-05-15

    The persistent environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an ovarian toxicant. These studies were designed to characterize the actions of TCDD on steroidogenesis and growth of intact mouse antral follicles in vitro. Specifically, these studies tested the hypothesis that TCDD exposure leads to decreased sex hormone production/secretion by antral follicles as well as decreased growth of antral follicles in vitro. Since TCDD acts through binding to the aryl hydrocarbon receptor (AHR), and the AHR has been identified as an important factor in ovarian function, we also conducted experiments to confirm the presence and activation of the AHR in our tissue culture system. To do so, we exposed mouse antral follicles for 96 h to a series of TCDD doses previously shown to have effects on ovarian tissues and cells in culture, which also encompass environmentally relevant and pharmacological exposures (0.1–100 nM), to determine a dose response for TCDD in our culture system for growth, hormone production, and expression of the Ahr and Cyp1b1. The results indicate that TCDD decreases progesterone, androstenedione, testosterone, and estradiol levels in a non-monotonic dose response manner without altering growth of antral follicles. The addition of pregnenolone substrate (10 μM) restores hormone levels to control levels. Additionally, Cyp1b1 levels were increased by 3–4 fold regardless of the dose of TCDD exposure, evidence of AHR activation. Overall, these data indicate that TCDD may act prior to pregnenolone formation and through AHR transcriptional control of Cyp1b1, leading to decreased hormone levels without affecting growth of antral follicles. -- Highlights: ►TCDD disrupts sex steroid hormone levels, but not growth of antral follicles. ►Pregnenolone co-treatment by-passes TCDD-induced steroid hormone disruption. ►TCDD affects steroid hormone levels through an AHR pathway in antral follicles.

  15. Identification of amino acid residues in the ligand-binding domain of the aryl hydrocarbon receptor causing the species-specific response to omeprazole: possible determinants for binding putative endogenous ligands.

    Science.gov (United States)

    Shiizaki, Kazuhiro; Ohsako, Seiichiroh; Kawanishi, Masanobu; Yagi, Takashi

    2014-02-01

    Omeprazole (OME) induces the expression of genes encoding drug-metabolizing enzymes, such as CYP1A1, via activation of the aryl hydrocarbon receptor (AhR) both in vivo and in vitro. However, the precise mechanism of OME-mediated AhR activation is still under investigation. While elucidating species-specific susceptibility to dioxin, we found that OME-mediated AhR activation was mammalian species specific. Moreover, we previously reported that OME has inhibitory activity toward CYP1A1 enzymes. From these observations, we speculated that OME-mediated AhR target gene transcription is due to AhR activation by increasing amounts of putative AhR ligands in serum by inhibition of CYP1A1 activity. We compared the amino acid sequences of OME-sensitive rabbit AhR and nonsensitive mouse AhR to identify the residues responsible for the species-specific response. Chimeric AhRs were constructed by exchanging domains between mouse and rabbit AhRs to define the region required for the response to OME. OME-mediated transactivation was observed only with the chimeric AhR that included the ligand-binding domain (LBD) of the rabbit AhR. Site-directed mutagenesis revealed three amino acids (M328, T353, and F367) in the rabbit AhR that were responsible for OME-mediated transactivation. Replacing these residues with those of the mouse AhR abolished the response of the rabbit AhR. In contrast, substitutions of these amino acids with those of the rabbit AhR altered nonsensitive mouse AhR to become sensitive to OME. These results suggest that OME-mediated AhR activation requires a specific structure within LBD that is probably essential for binding with enigmatic endogenous ligands.

  16. 2,3,7,8-Tetrachlorodibenzo-p-dioxin activates the aryl hydrocarbon receptor and alters sex steroid hormone secretion without affecting growth of mouse antral follicles in vitro

    International Nuclear Information System (INIS)

    Karman, Bethany N.; Basavarajappa, Mallikarjuna S.; Craig, Zelieann R.; Flaws, Jodi A.

    2012-01-01

    The persistent environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an ovarian toxicant. These studies were designed to characterize the actions of TCDD on steroidogenesis and growth of intact mouse antral follicles in vitro. Specifically, these studies tested the hypothesis that TCDD exposure leads to decreased sex hormone production/secretion by antral follicles as well as decreased growth of antral follicles in vitro. Since TCDD acts through binding to the aryl hydrocarbon receptor (AHR), and the AHR has been identified as an important factor in ovarian function, we also conducted experiments to confirm the presence and activation of the AHR in our tissue culture system. To do so, we exposed mouse antral follicles for 96 h to a series of TCDD doses previously shown to have effects on ovarian tissues and cells in culture, which also encompass environmentally relevant and pharmacological exposures (0.1–100 nM), to determine a dose response for TCDD in our culture system for growth, hormone production, and expression of the Ahr and Cyp1b1. The results indicate that TCDD decreases progesterone, androstenedione, testosterone, and estradiol levels in a non-monotonic dose response manner without altering growth of antral follicles. The addition of pregnenolone substrate (10 μM) restores hormone levels to control levels. Additionally, Cyp1b1 levels were increased by 3–4 fold regardless of the dose of TCDD exposure, evidence of AHR activation. Overall, these data indicate that TCDD may act prior to pregnenolone formation and through AHR transcriptional control of Cyp1b1, leading to decreased hormone levels without affecting growth of antral follicles. -- Highlights: ►TCDD disrupts sex steroid hormone levels, but not growth of antral follicles. ►Pregnenolone co-treatment by-passes TCDD-induced steroid hormone disruption. ►TCDD affects steroid hormone levels through an AHR pathway in antral follicles.

  17. Aryl hydrocarbon receptor-dependent upregulation of Cyp1b1 by TCDD and diesel exhaust particles in rat brain microvessels

    Directory of Open Access Journals (Sweden)

    Jacob Aude

    2011-08-01

    Full Text Available Abstract Background AhR activates the transcription of several target genes including CYP1B1. Recently, we showed CYP1B1 as the major cytochrome P450 (CYP enzyme expressed in human brain microvessels. Here, we studied the effect of AhR activation by environmental pollutants on the expression of Cyp1b1 in rat brain microvessels. Methods Expression of AhR and Cyp1b1 was detected in isolated rat brain microvessels. AhR was immunovisualised in brain microvessel endothelial cells. The effect of AhR ligands on Cyp1b1 expression was studied using isolated brain microvessels after ex vivo and/or in vivo exposure to TCDD, heavy hydrocarbons containing diesel exhaust particles (DEP or Δ9-tetrahydrocannabinol (Δ9-THC. Results After ex vivo exposure to TCDD (a highly potent AhR ligand for 3 h, Cyp1b1 expression was significantly increased by 2.3-fold in brain microvessels. A single i.p. dose of TCDD also increased Cyp1b1 transcripts (22-fold and Cyp1b1 protein (2-fold in rat brain microvessels at 72 h after TCDD. Likewise, DEP treatment (in vivo and ex vivo strongly induced Cyp1b1 protein in brain microvessels. DEP-mediated Cyp1b1 induction was inhibited by actinomycin D, cycloheximide, or by an AhR antagonist. In contrast, a sub-chronic in vivo treatment with Δ9-THC once daily for 7 seven days had no effect on Cyp1b1 expression Conclusions Our results show that TCDD and DEP strongly induced Cyp1b1 in rat brain microvessels, likely through AhR activation.

  18. Superinduction of CYP1A1 in MCF10A cultures by cycloheximide, anisomycin, and puromycin: a process independent of effects on protein translation and unrelated to suppression of aryl hydrocarbon receptor proteolysis by the proteasome.

    Science.gov (United States)

    Joiakim, Aby; Mathieu, Patricia A; Elliott, Althea A; Reiners, John J

    2004-10-01

    Exposure of the human breast epithelial cell line MCF10A to > or = 1 microg/ml cycloheximide (CHX)-induced accumulations of CYP1A1 mRNA 6-fold greater than that achieved with only 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Cotreatment with CHX and TCDD caused superinduction of CYP1A1 with accumulations of CYP1A1 mRNA 30-fold greater than that achieved with only TCDD. Similar results were obtained with the protein translation inhibitors anisomycin (ANS) and puromycin (PUR). Intra- and interinhibitor comparisons of dose/concentration response curves demonstrated the absence of a quantitative relationship between [3H]leucine incorporation and CYP1A1 induction/superinduction. The inducing/superinducing activities of CHX were suppressed by coincubation with the aryl hydrocarbon receptor (AhR) antagonists alpha-naphthoflavone and 3'-methoxy-4'-nitroflavone (PD168641). Electrophoretic mobility shift assays demonstrated that nuclear extracts from CHX-treated and CHX + TCDD cotreated cultures formed approximately 58 and approximately 340% of the AhR/DNA complexes obtained with TCDD-treated cultures, respectively. In contrast, rat liver extracts did not form AhR/DNA complexes after in vitro transformation with CHX. AhR turnover in TCDD-treated hepatoma 1c1c7 cultures was suppressed by cotreatment with CHX. In contrast, CHX or ANS treatment of MCF10A cultures induced AhR loss and enhanced AhR loss in cultures cotreated with TCDD. Cotreatment with N-benzoyloxycarbonyl-(Z)-Leu-Leu-leucinal (MG132) but not leptomycin B suppressed AhR loss. Hence, in MCF10A cells, CHX is not an AhR agonist but can superinduce CYP1A1 via an AhR-dependent mechanism; CYP1A1 superinduction by translation inhibitors is neither quantitatively related to effects on protein synthesis nor due to a generalized prevention of AhR proteolysis, and proteasome-mediated degradation of the activated AhR can occur in the nucleus.

  19. Metformin inhibits 7,12-dimethylbenz[a]anthracene-induced breast carcinogenesis and adduct formation in human breast cells by inhibiting the cytochrome P4501A1/aryl hydrocarbon receptor signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Maayah, Zaid H. [Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451 (Saudi Arabia); Ghebeh, Hazem [Stem Cell & Tissue Re-Engineering, King Faisal Specialist Hospital and Research Center, Riyadh 11211 (Saudi Arabia); Alhaider, Abdulqader A. [Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451 (Saudi Arabia); Camel Biomedical Research Unit, College of Pharmacy and Medicine, King Saud University, Riyadh 11451 (Saudi Arabia); El-Kadi, Ayman O.S. [Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, Edmonton (Canada); Soshilov, Anatoly A.; Denison, Michael S. [Department of Environmental Toxicology, University of California at Davis, Davis, CA 95616 (United States); Ansari, Mushtaq Ahmad [Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451 (Saudi Arabia); Korashy, Hesham M., E-mail: hkorashy@ksu.edu.sa [Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451 (Saudi Arabia)

    2015-04-15

    Recent studies have established that metformin (MET), an oral anti-diabetic drug, possesses antioxidant activity and is effective against different types of cancer in several carcinogen-induced animal models and cell lines. However, whether MET can protect against breast cancer has not been reported before. Therefore, the overall objectives of the present study are to elucidate the potential chemopreventive effect of MET in non-cancerous human breast MCF10A cells and explore the underlying mechanism involved, specifically the role of cytochrome P4501A1 (CYP1A1)/aryl hydrocarbon receptor (AhR) pathway. Transformation of the MCF10A cells into initiated breast cancer cells with DNA adduct formation was conducted using 7,12-dimethylbenz[a]anthracene (DMBA), an AhR ligand. The chemopreventive effect of MET against DMBA-induced breast carcinogenesis was evidenced by the capability of MET to restore the induction of the mRNA levels of basic excision repair genes, 8-oxoguanine DNA glycosylase (OGG1) and apurinic/apyrimidinic endonuclease1 (APE1), and the level of 8-hydroxy-2-deoxyguanosine (8-OHdG). Interestingly, the inhibition of DMBA-induced DNA adduct formation was associated with proportional decrease in CYP1A1 and in NAD(P)H:quinone oxidoreductase 1 (NQO1) gene expression. Mechanistically, the involvements of AhR and nuclear factor erythroid 2-related factor-2 (Nrf2) in the MET-mediated inhibition of DMBA-induced CYP1A1 and NQO1 gene expression were evidenced by the ability of MET to inhibit DMBA-induced xenobiotic responsive element and antioxidant responsive element luciferase reporter gene expression which suggests an AhR- and Nrf2-dependent transcriptional control. However, the inability of MET to bind to AhR suggests that MET is not an AhR ligand. In conclusion, the present work shows a strong evidence that MET inhibits the DMBA-mediated carcinogenicity and adduct formation by inhibiting the expression of CYP1A1 through an AhR ligand-independent mechanism

  20. Craniofacial form is altered by chronic adult exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD in Han/Wistar and Long–Evans rats with different aryl hydrocarbon receptor (AhR structures

    Directory of Open Access Journals (Sweden)

    Sabrina B. Sholts

    2015-01-01

    Full Text Available Mammalian bone has shown a variety of responses to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD exposure in experimental and wildlife studies. Although many responses have been well characterized in the postcranial skeleton, dioxin-induced effects on the cranium are largely unknown. In this study, we investigated the effects of chronic adult exposure to TCDD on cranial size and shape in dioxin-resistant Han/Wistar (H/W and dioxin-sensitive Long–Evans (L–E rat strains. Three-dimensional landmark configurations for the face, vault, and base of the cranium were recorded and analyzed using geometric morphometrics (GM and dose–response modeling. The strongest effects were shown by L–E and H/W rats with daily exposures of 100 and 1000 ng TCDD/kg bw/day, respectively, resulting in significant reductions in centroid size (CS in all three cranial modules for both strains except for the vault in H/W rats. Consistent with previous evidence of intraspecific variation in TCDD resistance, the benchmark doses (CEDs for cranial size reduction in L–E rats were roughly 10-fold lower than those for H/W rats. For both strains, the face showed the greatest size reduction from the highest doses of TCDD (i.e., 3.6 and 6.3% decreases in H/W and L–E rats, respectively, most likely related to dose-dependent reductions in limb bone size and body weight gain. However, intrinsic morphological differences between strains were also observed: although the control groups of H/W and L–E rats had vaults and bases of comparable size, the face was 6.4% larger in L–E rats. Thus, although H/W rats possess an altered aryl hydrocarbon receptor (AhR that appears to mediate and provides some resistance to TCDD exposure, their smaller reductions in facial size may also relate to strain-specific patterns of cranial development and growth. Future research will be aimed at understanding how ontogenetic factors may modulate toxic effects of prenatal and lactational exposure on

  1. Omeprazole induces NAD(P)H quinone oxidoreductase 1 via aryl hydrocarbon receptor-independent mechanisms: Role of the transcription factor nuclear factor erythroid 2–related factor 2

    International Nuclear Information System (INIS)

    Zhang, Shaojie; Patel, Ananddeep; Moorthy, Bhagavatula; Shivanna, Binoy

    2015-01-01

    Activation of the aryl hydrocarbon receptor (AhR) transcriptionally induces phase I (cytochrome P450 (CYP) 1A1) and phase II (NAD(P)H quinone oxidoreductase 1 (NQO1) detoxifying enzymes. The effects of the classical and nonclassical AhR ligands on phase I and II enzymes are well studied in human hepatocytes. Additionally, we observed that the proton pump inhibitor, omeprazole (OM), transcriptionally induces CYP1A1 in the human adenocarcinoma cell line, H441 cells via AhR. Whether OM activates AhR and induces the phase II enzyme, NAD(P)H quinone oxidoreductase 1 (NQO1), in fetal primary human pulmonary microvascular endothelial cells (HPMEC) is unknown. Therefore, we tested the hypothesis that OM will induce NQO1 in HPMEC via the AhR. The concentrations of OM used in our experiments did not result in cytotoxicity. OM activated AhR as evident by increased CYP1A1 mRNA expression. However, contrary to our hypothesis, OM increased NQO1 mRNA and protein via an AhR-independent mechanism as AhR knockdown failed to abrogate OM-mediated increase in NQO1 expression. Interestingly, OM activated Nrf2 as evident by increased phosphoNrf2 (S40) expression in OM-treated compared to vehicle-treated cells. Furthermore, Nrf2 knockdown abrogated OM-mediated increase in NQO1 expression. In conclusion, we provide evidence that OM induces NQO1 via AhR-independent, but Nrf2-dependent mechanisms. - Highlights: • We investigated whether omeprazole induces NQO1 in human fetal lung cells. • Omeprazole induces the phase II enzyme, NQO1, in human fetal lung cells. • AhR deficiency fails to abrogate omeprazole-mediated induction of NQO1. • Omeprazole increases phosphoNrf2 (S40) protein expression in human fetal lung cells. • Nrf2 knockdown abrogates the induction of NQO1 by omeprazole in human lung cells.

  2. Omeprazole induces NAD(P)H quinone oxidoreductase 1 via aryl hydrocarbon receptor-independent mechanisms: Role of the transcription factor nuclear factor erythroid 2–related factor 2

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Shaojie; Patel, Ananddeep; Moorthy, Bhagavatula; Shivanna, Binoy, E-mail: shivanna@bcm.edu

    2015-11-13

    Activation of the aryl hydrocarbon receptor (AhR) transcriptionally induces phase I (cytochrome P450 (CYP) 1A1) and phase II (NAD(P)H quinone oxidoreductase 1 (NQO1) detoxifying enzymes. The effects of the classical and nonclassical AhR ligands on phase I and II enzymes are well studied in human hepatocytes. Additionally, we observed that the proton pump inhibitor, omeprazole (OM), transcriptionally induces CYP1A1 in the human adenocarcinoma cell line, H441 cells via AhR. Whether OM activates AhR and induces the phase II enzyme, NAD(P)H quinone oxidoreductase 1 (NQO1), in fetal primary human pulmonary microvascular endothelial cells (HPMEC) is unknown. Therefore, we tested the hypothesis that OM will induce NQO1 in HPMEC via the AhR. The concentrations of OM used in our experiments did not result in cytotoxicity. OM activated AhR as evident by increased CYP1A1 mRNA expression. However, contrary to our hypothesis, OM increased NQO1 mRNA and protein via an AhR-independent mechanism as AhR knockdown failed to abrogate OM-mediated increase in NQO1 expression. Interestingly, OM activated Nrf2 as evident by increased phosphoNrf2 (S40) expression in OM-treated compared to vehicle-treated cells. Furthermore, Nrf2 knockdown abrogated OM-mediated increase in NQO1 expression. In conclusion, we provide evidence that OM induces NQO1 via AhR-independent, but Nrf2-dependent mechanisms. - Highlights: • We investigated whether omeprazole induces NQO1 in human fetal lung cells. • Omeprazole induces the phase II enzyme, NQO1, in human fetal lung cells. • AhR deficiency fails to abrogate omeprazole-mediated induction of NQO1. • Omeprazole increases phosphoNrf2 (S40) protein expression in human fetal lung cells. • Nrf2 knockdown abrogates the induction of NQO1 by omeprazole in human lung cells.

  3. Inhibition of the aryl hydrocarbon receptor prevents Western diet-induced obesity. Model for AHR activation by kynurenine via oxidized-LDL, TLR2/4, TGFβ, and IDO1.

    Science.gov (United States)

    Moyer, Benjamin J; Rojas, Itzel Y; Kerley-Hamilton, Joanna S; Hazlett, Haley F; Nemani, Krishnamurthy V; Trask, Heidi W; West, Rachel J; Lupien, Leslie E; Collins, Alan J; Ringelberg, Carol S; Gimi, Barjor; Kinlaw, William B; Tomlinson, Craig R

    2016-06-01

    Obesity is an increasingly urgent global problem, yet, little is known about its causes and less is known how obesity can be effectively treated. We showed previously that the aryl hydrocarbon receptor (AHR) plays a role in the regulation of body mass in mice fed Western diet. The AHR is a ligand-activated nuclear receptor that regulates genes involved in a number of biological pathways, including xenobiotic metabolism and T cell polarization. This study was an investigation into whether inhibition of the AHR prevents Western diet-based obesity. Male C57Bl/6J mice were fed control and Western diets with and without the AHR antagonist α-naphthoflavone or CH-223191, and a mouse hepatocyte cell line was used to delineate relevant cellular pathways. Studies are presented showing that the AHR antagonists α-naphthoflavone and CH-223191 significantly reduce obesity and adiposity and ameliorates liver steatosis in male C57Bl/6J mice fed a Western diet. Mice deficient in the tryptophan metabolizing enzyme indoleamine 2,3-dioxygenase 1 (IDO1) were also resistant to obesity. Using an AHR-directed, luciferase-expressing mouse hepatocyte cell line, we show that the transforming growth factor β1 (TGFβ1) signaling pathway via PI3K and NF-κB and the toll-like receptor 2/4 (TLR2/4) signaling pathway stimulated by oxidized low-density lipoproteins via NF-κB, each induce luciferase expression; however, TLR2/4 signaling was significantly reduced by inhibition of IDO1. At physiological levels, kynurenine but not kynurenic acid (both tryptophan metabolites and known AHR agonists) activated AHR-directed luciferase expression. We propose a hepatocyte-based model, in which kynurenine production is increased by enhanced IDO1 activity stimulated by TGFβ1 and TLR2/4 signaling, via PI3K and NF-κB, to perpetuate a cycle of AHR activation to cause obesity; and inhibition of the AHR, in turn, blocks the cycle's output to prevent obesity. The AHR with its broad ligand binding specificity

  4. The Aryl Hydrocarbon Receptor and Food Allergy

    NARCIS (Netherlands)

    Schulz, V.J.

    2013-01-01

    Currently, food allergy is a major health problem with an estimated prevalence of about 5% in young children and 3-4% in adults and the prevalence is increasing. However, no cure or approved treatment is available, despite the increased knowledge of mechanisms playing a role in food allergy. The

  5. Enantioselective Copper-Catalyzed Arylation-Driven Semipinacol Rearrangement of Tertiary Allylic Alcohols with Diaryliodonium Salts.

    Science.gov (United States)

    Lukamto, Daniel H; Gaunt, Matthew J

    2017-07-12

    A copper-catalyzed enantioselective arylative semipinacol rearrangement of allylic alcohols using diaryliodonium salts is reported. Chiral Cu(II)-bisoxazoline catalysts initiate an electrophilic alkene arylation, triggering a 1,2-alkyl migration to afford a range of nonracemic spirocyclic ketones with high yields, diastereo- and enantioselectivities.

  6. Inhibition of the aryl hydrocarbon receptor prevents Western diet-induced obesity. Model for AHR activation by kynurenine via oxidized-LDL, TLR2/4, TGFβ, and IDO1

    International Nuclear Information System (INIS)

    Moyer, Benjamin J.; Rojas, Itzel Y.; Kerley-Hamilton, Joanna S.; Hazlett, Haley F.; Nemani, Krishnamurthy V.; Trask, Heidi W.; West, Rachel J.; Lupien, Leslie E.; Collins, Alan J.

    2016-01-01

    Obesity is an increasingly urgent global problem, yet, little is known about its causes and less is known how obesity can be effectively treated. We showed previously that the aryl hydrocarbon receptor (AHR) plays a role in the regulation of body mass in mice fed Western diet. The AHR is a ligand-activated nuclear receptor that regulates genes involved in a number of biological pathways, including xenobiotic metabolism and T cell polarization. This study was an investigation into whether inhibition of the AHR prevents Western diet-based obesity. Male C57Bl/6J mice were fed control and Western diets with and without the AHR antagonist α-naphthoflavone or CH-223191, and a mouse hepatocyte cell line was used to delineate relevant cellular pathways. Studies are presented showing that the AHR antagonists α-naphthoflavone and CH-223191 significantly reduce obesity and adiposity and ameliorates liver steatosis in male C57Bl/6J mice fed a Western diet. Mice deficient in the tryptophan metabolizing enzyme indoleamine 2,3-dioxygenase 1 (IDO1) were also resistant to obesity. Using an AHR-directed, luciferase-expressing mouse hepatocyte cell line, we show that the transforming growth factor β1 (TGFβ1) signaling pathway via PI3K and NF-κB and the toll-like receptor 2/4 (TLR2/4) signaling pathway stimulated by oxidized low-density lipoproteins via NF-κB, each induce luciferase expression; however, TLR2/4 signaling was significantly reduced by inhibition of IDO1. At physiological levels, kynurenine but not kynurenic acid (both tryptophan metabolites and known AHR agonists) activated AHR-directed luciferase expression. We propose a hepatocyte-based model, in which kynurenine production is increased by enhanced IDO1 activity stimulated by TGFβ1 and TLR2/4 signaling, via PI3K and NF-κB, to perpetuate a cycle of AHR activation to cause obesity; and inhibition of the AHR, in turn, blocks the cycle's output to prevent obesity. The AHR with its broad ligand binding

  7. [Fe(III)(F(20)-tpp)Cl] is an effective catalyst for nitrene transfer reactions and amination of saturated hydrocarbons with sulfonyl and aryl azides as nitrogen source under thermal and microwave-assisted conditions.

    Science.gov (United States)

    Liu, Yungen; Che, Chi-Ming

    2010-09-10

    [Fe(III)(F(20)-tpp)Cl] (F(20)-tpp=meso-tetrakis(pentafluorophenyl)porphyrinato dianion) is an effective catalyst for imido/nitrene insertion reactions using sulfonyl and aryl azides as nitrogen source. Under thermal conditions, aziridination of aryl and alkyl alkenes (16 examples, 60-95 % yields), sulfimidation of sulfides (11 examples, 76-96 % yields), allylic amidation/amination of α-methylstyrenes (15 examples, 68-83 % yields), and amination of saturated C--H bonds including that of cycloalkanes and adamantane (eight examples, 64-80 % yields) can be accomplished by using 2 mol % [Fe(III)(F(20)-tpp)Cl] as catalyst. Under microwave irradiation conditions, the reaction time of aziridination (four examples), allylic amination (five examples), sulfimidation (two examples), and amination of saturated C--H bonds (three examples) can be reduced by up to 16-fold (24-48 versus 1.5-6 h) without significantly affecting the product yield and substrate conversion.

  8. Direct N9-arylation of purines with aryl halides

    DEFF Research Database (Denmark)

    Larsen, Anders Foller; Ulven, Trond

    2014-01-01

    An efficient method for N-arylation of purines is reported. The N-arylation is catalysed by Cu(i) and 4,7-bis(2-hydroxyethylamino)-1,10-phenanthroline (BHPhen) in aqueous DMF or ethanol. The reaction generally proceeds with high selectivity for the N(9)-position.......An efficient method for N-arylation of purines is reported. The N-arylation is catalysed by Cu(i) and 4,7-bis(2-hydroxyethylamino)-1,10-phenanthroline (BHPhen) in aqueous DMF or ethanol. The reaction generally proceeds with high selectivity for the N(9)-position....

  9. Biogeochemistry of Halogenated Hydrocarbons

    Science.gov (United States)

    Adriaens, P.; Gruden, C.; McCormick, M. L.

    2003-12-01

    Halogenated hydrocarbons originate from both natural and industrial sources. Whereas direct anthropogenic emissions to the atmosphere and biosphere are often easy to assess, particularly when they are tied to major industrial activities, the attribution of emissions to other human activities (e.g., biomass burning), diffuse sources (e.g., atmospheric discharge, run off), and natural production (e.g., soils, fungi, algae, microorganisms) are difficult to quantify. The widespread occurrence of both alkyl and aryl halides in groundwater, surface water, soils, and various trophic food chains, even those not affected by known point sources, suggests a substantial biogeochemical cycling of these compounds (Wania and Mackay, 1996; Adriaens et al., 1999; Gruden et al., 2003). The transport and reactive fate mechanisms controlling their reactivity are compounded by the differences in sources of alkyl-, aryl-, and complex organic halides, and the largely unknown impact of biogenic processes, such as enzymatically mediated halogenation of organic matter, fungal production of halogenated hydrocarbons, and microbial or abiotic transformation reactions (e.g., Asplund and Grimvall, 1991; Gribble, 1996; Watling and Harper, 1998; Oberg, 2002). The largest source may be the natural halogenation processes in the terrestrial environment, as the quantities detected often exceed the amount that can be explained by human activities in the surrounding areas ( Oberg, 1998). Since biogeochemical processes result in the distribution of a wide range of halogenated hydrocarbon profiles, altered chemical structures, and isomer distributions in natural systems, source apportionment (or environmental forensics) can often only be resolved using multivariate statistical methods (e.g., Goovaerts, 1998; Barabas et al., 2003; Murphy and Morrison, 2002).This chapter will describe the widespread occurrence of halogenated hydrocarbons, interpret their distribution and biogeochemical cycling in light of

  10. In vitro screening for aryl hydrocarbon receptor agonistic activity in 200 pesticides using a highly sensitive reporter cell line, DR-EcoScreen cells, and in vivo mouse liver cytochrome P450-1A induction by propanil, diuron and linuron.

    Science.gov (United States)

    Takeuchi, Shinji; Iida, Mitsuru; Yabushita, Hisatoshi; Matsuda, Tadashi; Kojima, Hiroyuki

    2008-12-01

    The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that regulates genes involved in xenobiotic metabolism, cellular proliferation and differentiation. In this study, we have developed a highly sensitive AhR-mediated reporter cell line, DR-EcoScreen cells, which are mouse hepatoma Hepa1c1c7 cells stably transfected with a reporter plasmid containing seven copies of dioxin-responsive element. Using these DR-EcoScreen cells, we performed the reporter gene assay and characterized the AhR agonistic activities of 200 pesticides (29 organochlorines, 11 diphenyl ethers, 56 organophosphorus pesticides, 12 pyrethroids, 22 carbamates, 12 acid amides, 7 triazines, 6 ureas, and 45 others). Eleven of the 200 pesticides (acifluorfen-methyl, bifenox, chlorpyrifos, isoxathion, quinalphos, chlorpropham, diethofencarb, propanil, diuron, linuron, and prochloraz) showed AhR-mediated transcriptional activity. In particular, three herbicides (propanil, diuron, and linuron) have a common chemical structure and showed more potent agonistic activity than other pesticides. To investigate the in vivo effects, we examined the gene expression of AhR-inducible cytochrome P450 1As (CYP1As) in the liver of female C57BL/6 mice intraperitoneally injected with these three herbicides (300 mg kg(-1)) by quantitative RT-PCR, resulting in induction of significant high levels of CYP1A1 and CYP1A2 mRNAs. This indicates that propanil, diuron and linuron possess AhR-mediated transactivation effect in vivo as well as in vitro. Through the present study, we demonstrated that DR-EcoScreen cells are useful for sensitive, rapid and simple identification of AhR agonists among a large number of environmental chemicals.

  11. Pot-Economy Autooxidative Condensation of 2-Aryl-2-lithio-1,3-dithianes.

    Science.gov (United States)

    Vale, João R; Rimpiläinen, Tatu; Sievänen, Elina; Rissanen, Kari; Afonso, Carlos A M; Candeias, Nuno R

    2018-02-16

    The autoxidative condensation of 2-aryl-2-lithio-1,3-dithianes is here reported. Treatment of 2-aryl-1,3-dithianes with n-BuLi in the absence of any electrophile leads to condensation of three molecules of 1,3-dithianes and formation of highly functionalized α-thioether ketones orthothioesters in 51-89% yields upon air exposure. The method was further expanded to benzaldehyde dithioacetals, affording corresponding orthothioesters and α-thioether ketones in 48-97% yields. The experimental results combined with density functional theory studies support a mechanism triggered by the autoxidation of 2-aryl-2-lithio-1,3-dithianes to yield a highly reactive thioester that undergoes condensation with two other molecules of 2-aryl-2-lithio-1,3-dithiane.

  12. Hexachlorobenzene induces cell proliferation, and aryl hydrocarbon receptor expression (AhR) in rat liver preneoplastic foci, and in the human hepatoma cell line HepG2. AhR is a mediator of ERK1/2 signaling, and cell cycle regulation in HCB-treated HepG2 cells.

    Science.gov (United States)

    de Tomaso Portaz, Ana Clara; Caimi, Giselle Romero; Sánchez, Marcela; Chiappini, Florencia; Randi, Andrea S; Kleiman de Pisarev, Diana L; Alvarez, Laura

    2015-10-02

    Hexachlorobenzene (HCB) is a widespread environmental pollutant, and a liver tumor promoter in rodents. Depending on the particular cell lines studied, exposure to these compounds may lead to cell proliferation, terminal differentiation, or apoptosis. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is involved in drug and xenobiotic metabolism. AhR can also modulate a variety of cellular and physiological processes that can affect cell proliferation and cell fate determination. The mechanisms by which AhR ligands, both exogenous and endogenous, affect these processes involve multiple interactions between AhR and other signaling pathways. In the present study, we examined the effect of HCB on cell proliferation and AhR expression, using an initiation-promotion hepatocarcinogenesis protocol in rat liver and in the human-derived hepatoma cell line, HepG2. Female Wistar rats were initiated with a single dose of 100 mg/kg of diethylnitrosamine (DEN) at the start of the experiment. Two weeks later, daily dosing of 100 mg/kg HCB was maintained for 10 weeks. Partial hepatectomy was performed 3 weeks after initiation. The number and area of glutathione S-transferase-P (GST-P)-positive foci, in the rat liver were used as biomarkers of liver precancerous lesions. Immunohistochemical staining showed an increase in proliferating cell nuclear antigen (PCNA)-positive cells, along with enhanced AhR protein expression in hepatocytes within GST-P-positive foci of (DEN HCB) group, when compared to DEN. In a similar manner, Western blot analysis demonstrated that HCB induced PCNA and AhR protein expression in HepG2 cells. Flow cytometry assay indicated that the cells were accumulated at S and G2/M phases of the cell cycle. HCB increased cyclin D1 protein levels and ERK1/2 phosphorylation in a dose-dependent manner. Treatment of cells with a selective MEK1 inhibitor, prevented HCB-stimulatory effect on PCNA and cyclinD1, indicating that these effects

  13. Synthesis of quaternary aryl phosphonium salts: photoredox-mediated phosphine arylation.

    Science.gov (United States)

    Fearnley, A F; An, J; Jackson, M; Lindovska, P; Denton, R M

    2016-04-11

    We report a synthesis method for the construction of quaternary aryl phoshonium salts at ambient temperature. The regiospecific reaction involves the coupling of phosphines with aryl radicals derived from diaryliodonium salts under photoredox conditions.

  14. Synthesis of Aryl-(E)-2-(azidomethyl)alkenoate and Aryl-(Z)-2-(azidomethyl)acrylonitrile from Aryl Aldehydes and Activated Alkenes via One-Pot Way

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sang-Jin; Yang, Hae-Won; Han, Tae-Hwi; Yoon, Cheol Min [Korea University, Sejong (Korea, Republic of)

    2016-05-15

    Aryl-(E)-2-(azidomethyl)alkenoate and aryl-(Z)-2-(azidomethyl)acrylonitrile from aryl aldehydes and activated alkenes (acrylate and acrylonitrile) were synthesized in one-pot consecutive way with excellent stereoselectivity in good to high yield. The method include a three-step one-pot processes: Baylis-Hillman reaction of aryl aldehydes and activated alkenes using DABCO followed by acetylation using acetic anhydride and a catalytic amount of DMAP and nucleophilic substitution using sodium azide in DMF at room temperature. Our one-pot synthetic protocol is efficient and simple. Organoazides are one of the most important synthetic intermediates for the preparation of nitrogen-containing organic compounds, for example, amines via reduction, imines via rearrangement, and other nitrogen-containing heterocycles via cycloaddition reactions. Because allyl azides among them are versatile building skeletons for the synthesis of biologically active nitrogen-containing heterocycles, the synthesis of allyl azides have become an attractive research area.

  15. Trigger finger

    Science.gov (United States)

    ... digit; Trigger finger release; Locked finger; Digital flexor tenosynovitis ... cut or hand Yellow or green drainage from the cut Hand pain or discomfort Fever If your trigger finger returns, call your surgeon. You may need another surgery.

  16. In silico prediction of harmful effects triggered by drugs and chemicals

    International Nuclear Information System (INIS)

    Vedani, Angelo; Dobler, Max; Lill, Markus A.

    2005-01-01

    While the computer-assisted discovery and optimization of drug candidates based on the known three-dimensional structure of the macromolecular target (structure-based design) or a binding-site surrogate (receptor modeling) is doubtless one of the more potent approaches in rational drug design, the simulation and quantification of side effects triggered by drugs and chemicals are still in their infancy. Major obstacles include the often not available 3D structure of the molecular target, the low specificity of the involved bioregulators and the identification of the controlling metabolic pathways. In the recent past, our laboratory has explored concepts allowing to simulate receptor-mediated toxic phenomena by developing algorithms, allowing to construct realistic 3D binding-site surrogates of receptors known or assumed triggering adverse effects and validating them against large batches of molecular data. The underlying technology (software Quasar and Raptor, respectively) specifically allows for induced fit, solvation phenomena and entropic effects. It has been applied to various systems both of pharmacological and toxicological interest including the neurokinin-1, chemokine-3, bradykinin B 2 , steroid, 5 HT 2A , aryl hydrocarbon, estrogen and androgen receptor, respectively. In this account, we describe the design of a virtual laboratory allowing for a reliable estimation of harmful effects triggered by drugs, chemicals and their metabolites in silico. In the recent past, the Biographics Laboratory 3R has compiled a 3D database including the surrogates of three major receptor systems known to mediate adverse effects (the aryl hydrocarbon, the estrogen and the androgen receptor, respectively) and validated them against a total of 345 compounds (drugs, chemicals, toxins) using multidimensional QSAR technologies. Within this pilot project, we could demonstrate that our virtual laboratory is able to both recognize toxic compounds substantially different from those

  17. Synthesis of Dimethyl Aryl Acylsulfonium Bromides from Aryl Methyl Ketones in a DMSO-HBr System

    Directory of Open Access Journals (Sweden)

    Zhiling Cao

    2013-12-01

    Full Text Available A new, simplified method for the synthesis of dimethyl aryl acylsulfonium salts has been developed. A series of dimethyl aryl acylsulfonium bromides were prepared by the reaction of aryl methyl ketones with hydrobromic acid and dimethylsulfoxide (DMSO. This sulfonium salt confirms that bromine production and the bromination reaction take place in the DMSO-HBr oxidation system. What’s more, it is also a key intermediate for the synthesis of arylglyoxals.

  18. Synthesis of dimethyl aryl acylsulfonium bromides from aryl methyl ketones in a DMSO-HBr system.

    Science.gov (United States)

    Cao, Zhiling; Shi, Dahua; Qu, Yingying; Tao, Chuanzhou; Liu, Weiwei; Yao, Guowei

    2013-12-16

    A new, simplified method for the synthesis of dimethyl aryl acylsulfonium salts has been developed. A series of dimethyl aryl acylsulfonium bromides were prepared by the reaction of aryl methyl ketones with hydrobromic acid and dimethylsulfoxide (DMSO). This sulfonium salt confirms that bromine production and the bromination reaction take place in the DMSO-HBr oxidation system. What's more, it is also a key intermediate for the synthesis of arylglyoxals.

  19. Mild copper-catalyzed N-arylation of azaheterocycles with aryl halides

    NARCIS (Netherlands)

    Kuil, M.; Bekedam, E.K.; Visser, G.M.; Hoogenband, van den A.; Terpstra, J.W.; Kamer, P.C.J.; Leeuwen, P.W.N.M.; Strijdonck, G.P.F.

    2005-01-01

    A highly efficient copper(I)-catalyzed N-arylation of azaheterocycles with various aryl halides is reported. The N-arylation reaction can be carried out using as low as 0.5 mol % of (Cu(I)OTf)2¿PhH and 1.0 mol % of 4,7-dichloro-1,10-phenanthroline as the ligand. Furthermore, cheap and stable copper

  20. Petroleum hydrocarbons

    International Nuclear Information System (INIS)

    Farrington, J.W.; Teal, J.M.; Parker, P.L.

    1976-01-01

    Methods for analysis of petroleum hydrocarbons in marine samples are presented. Types of hydrocarbons present and their origins are discussed. Principles and methods of analysis are outlined. Infrared spectrometry, uv spectrometry, gas chromatography, mass spectroscopy, and carbon 14 measurements are described

  1. Palladium-catalysed ortho arylation of acetanilides

    Indian Academy of Sciences (India)

    Full Papers Volume 122 Issue 2 March 2010 pp 149-155 ... Abstract. The palladium-catalysed direct arylation of acetanilides by using C-H activation methodology has been demonstrated. Several acetanilides were coupled with aryl iodides in the presence of 10 mol% of Pd(OAc)2, 1.0 equiv of Cu(OTf)2, and 0.6 equiv of ...

  2. Copper-catalysed N-arylation of arylsulfonamides with aryl bromides ...

    Indian Academy of Sciences (India)

    An efficient synthesis of -arylsulfonamides with a variety of aryl bromides, aryl iodides and heteroaryl bromides using KF/Al2O3 as a suitable base, CuI as an inexpensive catalyst and ,'-dimethylethylenediamine (,'-DMEDA) as an effective ligand is described.

  3. Biological processes for the production of aryl sulfates

    DEFF Research Database (Denmark)

    2016-01-01

    The present invention generally relates to the field of biotechnology as it applies to the production of aryl sulfates using polypeptides or recombinant cells comprising said polypeptides. More particularly, the present invention pertains to polypeptides having aryl sulfotransferase activity......, recombinant host cells expressing same and processes for the production of aryl sulfates employing these polypeptides or recombinant host cells....

  4. Oral Methylated N-Aryl Chitosan Derivatives for Inducing Immune ...

    African Journals Online (AJOL)

    aryl chitosan derivatives. The N-aryl chitosan derivatives were carried out in accordance with the previous reported procedure [9] whereas the methylation of chitosan and N-aryl chitosan derivatives have been carried out by a single treatment ...

  5. Electronic structure and tautomerism of aryl ketones

    Energy Technology Data Exchange (ETDEWEB)

    Novak, Igor, E-mail: inovak@csu.edu.au [Charles Sturt University, POB 883, Orange, NSW 2800 (Australia); Klasinc, Leo, E-mail: klasinc@irb.hr [Physical Chemistry Department, Ruđer Bošković Institute, HR-10002 Zagreb (Croatia); Šket, Boris, E-mail: Boris.Sket@fkkt.uni-lj.si [Faculty of Chemistry and Chemical Technology, University of Ljubljana, SI-1000 (Slovenia); McGlynn, S.P., E-mail: sean.mcglynn@chemgate.chem.lsu.edu [Louisiana State University, Baton Rouge, LA 70803 (United States)

    2015-07-15

    Graphical abstract: Photoelectron spectroscopy, tautomerism. - Highlights: • UV photoelectron spectroscopy of aryl ketones. • The relative stability of tautomers and their electronic structures. • The factors influencing tautomerism. - Abstract: The electronic structures of several aryl ketones (AK) and their α-halo derivatives have been studied by UV photoelectron spectroscopy (UPS). The relative stabilities of keto–enol tautomers have been determined using high-level ab initio calculations and the results were used in the analysis of UPS spectra. The main features of electronic structure and tautomerism of the AK derivatives are discussed.

  6. Catalytic Asymmetric Alkylation of Aryl Heteroaryl Ketones

    NARCIS (Netherlands)

    Ortiz, Pablo; Harutyunyan, Syuzanna; del Hoyo, Ana

    Tertiary diarylmethanols are highly bioactive structural motifs. A new strategy to access chiral tertiary diarylmethanols through copper-catalyzed direct alkylation of (di)(hetero)aryl ketones by using Grignard reagents was developed. The low reactivity and the similarity of the enantiotopic faces

  7. Palladium-catalysed ortho arylation of acetanilides

    Indian Academy of Sciences (India)

    Administrator

    State Key Laboratory of Applied Organic Chemistry, Lanzhou 73000, P.R. China e-mail: hgs2368@163.com. MS received 12 January 2009; revised 20 July 2009; accepted 14 September 2009. Abstract. The palladium-catalysed direct arylation of acetanilides by using C–H activation methodo- logy has been demonstrated.

  8. Organic Transformations on σ-Aryl Organometallic

    NARCIS (Netherlands)

    Gagliardo, M.; Snelders, D.J.M.|info:eu-repo/dai/nl/304836257; Chase, P.A.; Klein Gebbink, R.J.M.|info:eu-repo/dai/nl/166032646; van Klink, G.P.M.|info:eu-repo/dai/nl/170637964; van Koten, G.|info:eu-repo/dai/nl/073839191

    2007-01-01

    This work reviews recent developments in the field of organic transformations on σ-aryl organometallic complexes. The general notion that M-C bonds are kinetically labile, highly reactive, and incompatible with typical reaction conditions met in organic synthesis has limited the use of these

  9. Pd-catalyzed regioselective arylation on the C-5 position of N-aryl 1,2,3-triazoles.

    Science.gov (United States)

    Yamajala, K Durga Bhaskar; Patil, Mahendra; Banerjee, Shaibal

    2015-03-20

    We herein report a highly efficient method for the arylation at the C-5 position of N-aryl 1,2,3-triazoles via a direct palladium catalyzed arylation reaction. The optimal reaction conditions required a combination of Pd(OAc)2 and tris(o-tolyl)phosphine as catalyst, and Cs2CO3 as the base under inert atmosphere. A variety of C-5 substituted N-aryl 1,2,3-triazoles were prepared using these conditions with yields in the 70-88% range. Regioselective C-5 arylations were also performed on 1,4-disubstituted 1,2,3-triazoles. The regioselectivity in triazole substitution at the C-5 position was confirmed by single crystal XRD. In addition, computational investigations of key steps of the catalytic cycle using the density functional theory have provided a rationalization to the selective C-5 arylation of N-aryl 1,2,3-triazoles.

  10. Multimetallic catalysed cross-coupling of aryl bromides with aryl triflates

    Science.gov (United States)

    Ackerman, Laura K. G.; Lovell, Matthew M.; Weix, Daniel J.

    2015-08-01

    The advent of transition-metal catalysed strategies for forming new carbon-carbon bonds has revolutionized the field of organic chemistry, enabling the efficient synthesis of ligands, materials, and biologically active molecules. In cases where a single metal fails to promote a selective or efficient transformation, the synergistic cooperation of two distinct catalysts--multimetallic catalysis--can be used instead. Many important reactions rely on multimetallic catalysis, such as the Wacker oxidation of olefins and the Sonogashira coupling of alkynes with aryl halides, but this approach has largely been limited to the use of metals with distinct reactivities, with only one metal catalyst undergoing oxidative addition. Here, we demonstrate that cooperativity between two group 10 metal catalysts--(bipyridine)nickel and (1,3-bis(diphenylphosphino)propane)palladium--enables a general cross-Ullmann reaction (the cross-coupling of two different aryl electrophiles). Our method couples aryl bromides with aryl triflates directly, eliminating the use of arylmetal reagents and avoiding the challenge of differentiating between multiple carbon-hydrogen bonds that is required for direct arylation methods. Selectivity can be achieved without an excess of either substrate and originates from the orthogonal reactivity of the two catalysts and the relative stability of the two arylmetal intermediates. While (1,3-bis(diphenylphosphino)propane)palladium reacts preferentially with aryl triflates to afford a persistent intermediate, (bipyridine)nickel reacts preferentially with aryl bromides to form a transient, reactive intermediate. Although each catalyst forms less than 5 per cent cross-coupled product in isolation, together they are able to achieve a yield of up to 94 per cent. Our results reveal a new method for the synthesis of biaryls, heteroaryls, and dienes, as well as a general mechanism for the selective transfer of ligands between two metal catalysts. We anticipate that this

  11. Triggering Artefacts

    DEFF Research Database (Denmark)

    Mogensen, Preben Holst; Robinson, Mike

    1995-01-01

    The paper presents a general critique of the use of conceptual frameworks in design, illustrated by the well known synchronous/asynchronous, co-located/non-co-located framework. It argues that while frameworks are a necessary and inevitable starting point for design, the business of tailoring...... and adapting them to specific situations need not be ad hoc.Triggering artefacts are a way of systematically challenging both designers' preunderstandings and the conservatism of work practice. Experiences from the Great Belt tunnel and bridge project are used to illustrate howtriggering artefacts change...

  12. Organocatalytic asymmetric arylation of indoles enabled by azo groups

    Science.gov (United States)

    Qi, Liang-Wen; Mao, Jian-Hui; Zhang, Jian; Tan, Bin

    2018-01-01

    Arylation is a fundamental reaction that can be mostly fulfilled by electrophilic aromatic substitution and transition-metal-catalysed aryl functionalization. Although the azo group has been used as a directing group for many transformations via transition-metal-catalysed aryl carbon-hydrogen (C-H) bond activation, there remain significant unmet challenges in organocatalytic arylation. Here, we show that the azo group can effectively act as both a directing and activating group for organocatalytic asymmetric arylation of indoles via formal nucleophilic aromatic substitution of azobenzene derivatives. Thus, a wide range of axially chiral arylindoles have been achieved in good yields with excellent enantioselectivities by utilizing chiral phosphoric acid as catalyst. Furthermore, highly enantioenriched pyrroloindoles bearing two contiguous quaternary chiral centres have also been obtained via a cascade enantioselective formal nucleophilic aromatic substitution-cyclization process. This strategy should be useful in other related research fields and will open new avenues for organocatalytic asymmetric aryl functionalization.

  13. Palladium-Catalyzed Synthesis of N-Aryl Carbamates

    Science.gov (United States)

    Vinogradova, Ekaterina V.; Park, Nathaniel H.; Fors, Brett P.; Buchwald, Stephen L.

    2013-01-01

    An efficient synthesis of aryl carbamates was achieved by introducing alcohols into the reaction of palladium-catalyzed cross-coupling of ArX (X = Cl, OTf) with sodium cyanate. The use of aryl triflates as electrophilic components in this transformation allowed for an expanded substrate scope for direct synthesis of aryl isocyanates. This methodology provides direct access to major carbamate protecting groups, S-thiocarbamates, and diisocyanate precursors to polyurethane materials. PMID:23441814

  14. Palladium-Catalyzed Arylation of Fluoroalkylamines

    Science.gov (United States)

    Brusoe, Andrew T.; Hartwig, John F.

    2015-01-01

    We report the synthesis of fluorinated anilines by palladium-catalyzed coupling of fluoroalkylamines with aryl bromides and aryl chlorides. The products of these reactions are valuable because anilines typically require the presence of an electron-withdrawing substituent on nitrogen to suppress aerobic or metabolic oxidation, and the fluoroalkyl groups have steric properties and polarity distinct from those of more common electron-withdrawing amide and sulfonamide units. The fluoroalkylaniline products are unstable under typical conditions for C–N coupling reactions (heat and strong base). However, the reactions conducted with the weaker base KOPh, which has rarely been used in cross-coupling to form C–N bonds, occurred in high yield in the presence of a catalyst derived from commercially available AdBippyPhos and [Pd(allyl)Cl]2. Under these conditions, the reactions occur with low catalyst loadings (<0.50 mol % for most substrates) and tolerate the presence of various functional groups that react with the strong bases that are typically used in Pd-catalyzed C–N cross-coupling reactions of aryl halides. The resting state of the catalyst is the phenoxide complex, (BippyPhosPd(Ar)OPh); due to the electron-withdrawing property of the fluoroalkyl substituent, the turnover-limiting step of the reaction is reductive elimination to form the C–N bond. PMID:26065341

  15. Palladium-Catalyzed alpha-Arylation of Tetramic Acids

    DEFF Research Database (Denmark)

    Storgaard, Morten; Dorwald, F. Z.; Peschke, B.

    2009-01-01

    A mild, racemization-free, palladium-Catalyzed alpha-arylation of tetramic acids (2,4-pyrrolidinediones) has been developed. Various amino acid-derived tetramic acids were cleanly arylated by treatment with 2 mol % of Pd(OAc)(2), 4 mol % of a sterically demanding biaryl phosphine, 2.3 equiv of K2CO...... no effect on their reactivity: both electron-rich and electron-poor aryl chlorides and bromides or triflates led to good yields. Ortho-substituted aryl halides and heteroaryl halides, however, did not undergo the title reaction....

  16. Palladium-Catalyzed Zinc-Amide-Mediated C-H Arylation of Fluoroarenes and Heteroarenes with Aryl Sulfides.

    Science.gov (United States)

    Otsuka, Shinya; Yorimitsu, Hideki; Osuka, Atsuhiro

    2015-10-12

    C-H arylation of polyfluoroarenes and heteroarenes with aryl sulfides proceeds smoothly with the aid of a palladium-N-heterocyclic carbene catalyst. A bulky zinc amide, TMPZnCl⋅LiCl, plays a key role as an effective base to generate the corresponding arylzinc species in situ. This arylation protocol is practically much easier to perform than our previous method, which necessitates preparation of the arylzinc reagents in advance from the corresponding aryl halides. Aryl sulfides that are prepared through sulfur-specific reactions, such as SN Ar sulfanylation and extended Pummerer reactions, undergo this direct arylation, offering interesting transformations that are otherwise difficult to achieve with conventional halogen-based organic synthesis. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Palladium-catalyzed cross-coupling reactions of aryl boronic acids with aryl halides in water.

    Science.gov (United States)

    Wang, Shaoyan; Zhang, Zhiqiang; Hu, Zhizhi; Wang, Yue; Lei, Peng; Chi, Haijun

    2009-01-01

    An efficient Suzuki cross-coupling reaction using a variety of aryl halides in neat water was developed. The Pd-catalyzed reaction between aryl bromides or chlorides and phenyl boronic acids was compatible with various functional groups and affords biphenyls in good to excellent yields without requirement of organic cosolvents. The air stability and solubility in water of the palladium-phosphinous acid complexes were considered to facilitate operation of the coupling reaction and product isolation. The reaction conditions including Pd catalyst selection, temperature, base and catalyst recoverability were also investigated.

  18. Hydrocarbon exploration

    Energy Technology Data Exchange (ETDEWEB)

    Lerche, I. (South Carolina Univ., Columbia, SC (United States). Dept. of Geological Sciences)

    1993-01-01

    This special issue of the journal examines various aspects of the on-going search for hydrocarbons, ranging from frontier basins where little data are available, to more mature areas where considerable data are available. The incentives underlying the search for oil are roughly: the social, economic and industrial needs of a nation; the incentive of a corporation to be profitable; and the personal incentives of individuals in the oil industry and governments, which range from financial wealth to power and which are as diverse as the individuals who are involved. From a geopolitical perspective, the needs, requirements, goals, strategies, and philosophies of nations, and groups of nations, also impact on the oil exploration game. Strategies that have been employed have ranged from boycott to austerity and rationing, to physical intervention, to global ''flooding'' with oil by over-production. (author)

  19. Copper-catalysed N-arylation of arylsulfonamides with aryl bromides ...

    Indian Academy of Sciences (India)

    Administrator

    fonamides with aryl halides. 8–10. However, many of reported procedures have drawbacks such as long reaction time, harsh reaction conditions, use of hygroscopic Cs2CO3 as base and carrying out reac- tion in a sealed tube. The application of KF/Al2O3 to organic synthesis has provided new methods for a wide array of ...

  20. Mechanism-based inactivation of benzo[a]pyrene hydroxylase by aryl acetylenes and aryl olefins

    International Nuclear Information System (INIS)

    Gan, L.S.; Lu, J.Y.L.; Alworth, W.L.

    1986-01-01

    A series of aryl acetylenes and aryl olefins have been examined as substrates and inhibitors of cytochrome P-450 dependent monooxgenases in liver microsomes from 5,6-benzoflavone or phenobarbital pretreated rats. 1-Ethynylpyrene, 3-ethynylperylene, 2-ethynylfluorene, methyl 1-pyrenyl acetylene, cis- and trans-1-(2-bromovinyl)pyrene, and 1-allylpyrene serve as mechanism-based irreversible inactivators (suicide inhibitors) of benzo[a]pyrene hydroxylase, while 1-vinylpyrene and phenyl 1-pyrenyl acetylene do not cause a detectable suicide inhibition of benzo[a]pyrene hydroxylase. The mechanism-based loss of benzo[a]pyrene hydroxylase caused by the aryl acetylenes is not accompanied by a corresponding loss of the P-450 content of the microsomes (suicide destruction). The suicide inhibition by these aryl acetylenes therefore does not involve covalent binding to the heme moiety of the monooxygenase. Nevertheless, in the presence of NADPH, 3 H-labeled 1-ethynylpyrene becomes covalently attached to the cytochrome P-450 protein; the measured stoichiometry of binding is one 1-ethynylpyrene per P-450 heme unit. The authors conclude that the inhibition of benzo[a]pyrene hydroxylase produced by 1-ethynylpyrene may be related to the mechanism of suicide inhibition of P-450 activity by chloramphenicol rather than the mechanism of suicide destruction of P-450 previously described for acetylene and propyne

  1. Two expedient 'one-pot'methods for synthesis of -aryl- ...

    Indian Academy of Sciences (India)

    Keywords. -aryl--mercaptoketones; anhydrous potassium carbonate; amberlyst-15; chalcones; thia-Michael addition. Abstract. Two expedient one-pot methods have been developed for synthesis of -aryl--mercaptoketones using acetophenones, benzaldehydes and thiols as starting materials. The methods involve ...

  2. Rhodium(iii)-catalyzed ortho-olefination of aryl phosphonates.

    Science.gov (United States)

    Chary, Bathoju Chandra; Kim, Sunggak

    2013-09-25

    Rhodium(iii)-catalyzed C-H olefination of aryl phosphonic esters is reported for the first time. In this mild and efficient process, the phosphonic ester group is utilized successfully as a new directing group. In addition, mono-olefination for aryl phosphonates is observed using a phosphonic diamide directing group.

  3. Selective copper catalysed aromatic N-arylation in water

    DEFF Research Database (Denmark)

    Engel-Andreasen, Jens; Shimpukade, Bharat; Ulven, Trond.

    2013-01-01

    4,7-Dipyrrolidinyl-1,10-phenanthroline (DPPhen) was identified as an efficient ligand for copper catalyzed selective arom. N-arylation in water. N-Arylation of indoles, imidazoles and purines proceeds with moderate to excellent yields and complete selectivity over aliph. amines. Aq. medium...

  4. Alkyl and aryl phosphorodiiodidites. Pt. 2

    International Nuclear Information System (INIS)

    Feshchenko, N.G.; Kostina, V.G.

    1976-01-01

    Alkyl phosphorodiiodidites are formed in the reactions of alkyl phosphorodichloridites with lithium iodide. They are stable at -60 to -50 0 . When warmed to 20 0 , they disproportionate with conversion into trialkyl phosphites and phosphorus triiodide. The latter also react together and give alkyl iodides, diphosphorus tetraiodide, and a polymer of unestablished structure. Diaryl and dialkyl phosphoriodidites are stable only in solution at low temperatures. They disproportionate in a similar way to aryl and alkyl phosphorodiiodidites. Alkyl phosphorodiiodidites react with iodine with the formation of alkyl iodides and phosphoryl iodide

  5. The Barbier-Grignard-type arylation of aldehydes using unactivated aryl iodides in water.

    Science.gov (United States)

    Zhou, Feng; Li, Chao-Jun

    2014-06-26

    Carbon-carbon bond formation is the essence of organic synthesis. One of the most important methods for forming carbon-carbon bonds is the Barbier-Grignard-type reaction, which was discovered over a century ago. However, it is still highly desirable to further improve this process. In this article, we describe a Barbier-Grignard-type direct arylation of aldehydes by using unactivated iodides mediated by zinc and catalysed by rhodium in water. This method bypasses a number of challenges encountered by the conventional Barbier-Grignard reaction, such as strict exclusion of moisture and air, protection-deprotection of various acidic hydrogens in the substrates, and so forth. It thereby creates a safer, more convenient and more environmentally benign strategy to access the diarylmethanols and aryl alkyl alcohols, ubiquitous skeletons found in fine chemicals, biologically active molecules and pharmaceuticals. Importantly, the same reaction performed in an organic solvent proceeded sluggishly to give much inferior yields.

  6. Improved biological processes for the production of aryl sulfates

    DEFF Research Database (Denmark)

    2017-01-01

    The present invention generally relates to the field of biotechnology as it applies to the production of aryl sulfates using recombinant host cells. More particularly, the present invention pertains to recombinant host cells comprising (e.g., expressing) a polypeptide having aryl sulfotransferase...... activity, wherein said recombinant host cells have been modified to have an increased uptake of sulfate compared to identical host cells that does not carry said modification. Further provided are processes for the production of aryl sulfates, such as zosteric acid, employing such recombinant host cells....

  7. Synthesis of 3-fluoro-3-aryl oxindoles: Direct enantioselective α arylation of amides

    KAUST Repository

    Wu, Linglin

    2012-02-06

    Modus operandi: Catalytic access to the title compounds through a new asymmetric α-arylation protocol is reported (see scheme). These products are formed in good yields and excellent enantioselectivities by using a new and easily synthesized chiral N-heterocyclic carbene (NHC) ligand. Advanced DFT calculations reveal the properties of the NHC ligand and the mode of operation of the catalyst. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. The unexpected influence of aryl substituents in N-aryl-3-oxobutanamides on the behavior of their multicomponent reactions with 5-amino-3-methylisoxazole and salicylaldehyde

    Directory of Open Access Journals (Sweden)

    Volodymyr V. Tkachenko

    2014-12-01

    Full Text Available The switchable three-component reactions of 5-amino-3-methylisoxazole, salicylaldehyde and N-aryl-3-oxobutanamides under different conditions were studied and discussed. The unexpected influence of the aryl substituent in N-aryl-3-oxobutanamides on the behavior of the reaction was discovered. The key influence of ultrasonication and Lewis acid catalysts led to an established protocol to selectively obtain two or three types of heterocyclic scaffolds depending on the substituent in the N-aryl moiety.

  9. Metal free synthesis of functionalized 1-aryl isoquinolines via iodine ...

    Indian Academy of Sciences (India)

    KAMSALI MURALI MOHAN ACHARI

    Metal free synthesis of functionalized 1-aryl isoquinolines via iodine mediated oxidative dehydrogenation and ring opening of lactam in isoindoloisoquinolinones. KAMSALI MURALI MOHAN ACHARI, MUTHUPANDI KARTHICK and CHINNASAMY RAMARAJ RAMANATHAN. ∗. Department of Chemistry, Pondicherry ...

  10. Metal free synthesis of functionalized 1-aryl isoquinolines via iodine ...

    Indian Academy of Sciences (India)

    Metal free synthesis of functionalized 1-aryl isoquinolines via iodine mediated oxidative dehydrogenation and ring opening of lactam in isoindoloisoquinolinones. KAMSALI MURALI MOHAN ACHARI MUTHUPANDI KARTHICK CHINNASAMY RAMARAJ RAMANATHAN. Regular Aricle Volume 129 Issue 6 June 2017 pp ...

  11. The LHCb trigger

    International Nuclear Information System (INIS)

    Korolko, I.

    1998-01-01

    This paper describes progress in the development of the LHCb trigger system since the letter of intent. The trigger philosophy has significantly changed, resulting in an increase of trigger efficiency for signal B events. It is proposed to implement a level-1 vertex topology trigger in specialised hardware. (orig.)

  12. A room temperature copper catalyzed N-selective arylation of β-amino alcohols with iodoanilines and aryl iodides

    OpenAIRE

    Das, Priyabrata; De Brabander, Jef K.

    2013-01-01

    An efficient method is described for the synthesis of N-(2-aminophenyl)-2-hydroxyethylamines via a copper catalyzed N-selective arylation of β-amino alcohols with iodoanilines. The corresponding coupling products are useful intermediates for the synthesis of a variety of N-2-hydroxyethyl-substituted benzimidazoles, benzimidazolones, and iminobenzimidazoles. We found that 2-iodoaniline only arylates certain amino alcohols but not amines lacking a hydroxyl group. We also demonstrate the arylati...

  13. Myofascial trigger point pain.

    Science.gov (United States)

    Jaeger, Bernadette

    2013-01-01

    Myofascial trigger point pain is an extremely prevalent cause of persistent pain disorders in all parts of the body, not just the head, neck, and face. Features include deep aching pain in any structure, referred from focally tender points in taut bands of skeletal muscle (the trigger points). Diagnosis depends on accurate palpation with 2-4 kg/cm2 of pressure for 10 to 20 seconds over the suspected trigger point to allow the referred pain pattern to develop. In the head and neck region, cervical muscle trigger points (key trigger points) often incite and perpetuate trigger points (satellite trigger points) and referred pain from masticatory muscles. Management requires identification and control of as many perpetuating factors as possible (posture, body mechanics, psychological stress or depression, poor sleep or nutrition). Trigger point therapies such as spray and stretch or trigger point injections are best used as adjunctive therapy.

  14. The Central Trigger Processor (CTP)

    CERN Multimedia

    Franchini, Matteo

    2016-01-01

    The Central Trigger Processor (CTP) receives trigger information from the calorimeter and muon trigger processors, as well as from other sources of trigger. It makes the Level-1 decision (L1A) based on a trigger menu.

  15. Palladium-Catalyzed C-H Arylation of 1,2,3-Triazoles.

    Science.gov (United States)

    Zhang, Chengwei; You, Lin; Chen, Chuo

    2016-09-22

    Palladium(II) acetate, in combination with triphenylphosphine, catalyzes direct arylation of 1,4-disubstituted 1,2,3-triazoles effectively. This C-H arylation reaction provides facile access to fully substituted triazoles with well-defined regiochemistry.

  16. Common Asthma Triggers

    Science.gov (United States)

    ... Grass Other Triggers If you have asthma, an asthma attack can happen when you are exposed to “asthma ... a second person. Secondhand smoke can trigger an asthma attack. If you have asthma, people should never smoke ...

  17. The KLOE trigger system

    International Nuclear Information System (INIS)

    Adinolfi, M.; Aloisio, A.; Ambrosino, F.; Andryakov, A.; Antonelli, A.; Antonelli, M.; Anulli, F.; Bacci, C.; Bankamp, A.; Barbiellini, G.; Bellini, F.; Bencivenni, G.; Bertolucci, S.; Bini, C.; Bloise, C.; Bocci, V.; Bossi, F.; Branchini, P.; Bulychjov, S.A.; Cabibbo, G.; Calcaterra, A.; Caloi, R.; Campana, P.; Capon, G.; Carboni, G.; Cardini, A.; Casarsa, M.; Cataldi, G.; Ceradini, F.; Cervelli, F.; Cevenini, F.; Chiefari, G.; Ciambrone, P.; Conetti, S.; Conticelli, S.; De Lucia, E.; De Robertis, G.; De Sangro, R.; De Simone, P.; De Zorzi, G.; Dell'Agnello, S.; Denig, E.; Di Domenico, A.; Di Donato, C.; Di Falco, S.; Doria, A.; Drago, E.; Elia, V.; Erriquez, O.; Farilla, A.; Felici, G.; Ferrari, A.; Ferrer, M.L.; Finocchiaro, G.; Forti, C.; Franceschi, A.; Franzini, P.; Gao, M.L.; Gatti, C.; Gauzzi, P.; Giovannella, S.; Golovatyuk, V.; Gorini, E.; Grancagnolo, F.; Grandegger, W.; Graziani, E.; Guarnaccia, P.; Hagel, U. von; Han, H.G.; Han, S.W.; Huang, X.; Incagli, M.; Ingrosso, L.; Jang, Y.Y.; Kim, W.; Kluge, W.; Kulikov, V.; Lacava, F.; Lanfranchi, G.; Lee-Franzini, J.; Lomtadze, F.; Luisi, C.; Mao, C.S.; Martemianov, M.; Matsyuk, M.; Mei, W.; Merola, L.; Messi, R.; Miscetti, S.; Moalem, A.; Moccia, S.; Moulson, M.; Mueller, S.; Murtas, F.; Napolitano, M.; Nedosekin, A.; Panareo, M.; Pacciani, L.; Pages, P.; Palutan, M.; Paoluzi, L.; Pasqualucci, E.; Passalacqua, L.; Passaseo, M.; Passeri, A.; Patera, V.; Petrolo, E.; Petrucci, G.; Picca, D.; Pirozzi, G.; Pistillo, C.; Pollack, M.; Pontecorvo, L.; Primavera, M.; Ruggieri, F.; Santangelo, P.; Santovetti, E.; Saracino, G.; Schamberger, R.D.; Schwick, C.; Sciascia, B.; Sciubba, A.; Scuri, F.; Sfiligoi, I.; Shan, J.; Silano, P.; Spadaro, T.; Spagnolo, S.; Spiriti, E.; Stanescu, C.; Tong, G.L.; Tortora, L.; Valente, E.; Valente, P.; Valeriani, B.; Venanzoni, G.; Veneziano, S.; Wu, Y.; Xie, Y.G.; Zhao, P.P.; Zhou, Y.

    2001-01-01

    A double-level trigger system has been developed for the KLOE experiment. Custom electronics asserts a trigger in a 2 μs decision time. The decision is based on the combined information of the electromagnetic calorimeter and the drift chamber. The entire trigger system is continuously monitored, and data flowing from the trigger system have allowed both an efficient online monitoring of the detector and an online luminosity measurement

  18. Highly N2-Selective Palladium-Catalyzed Arylation of 1,2,3-Triazoles

    Science.gov (United States)

    Ueda, Satoshi; Su, Mingjuan; Buchwald, Stephen L.

    2012-01-01

    Highly N2-selective arylation of 4,5-unsubstituted and 4-substituted 1,2,3-triazoles was achieved for the first time by Pd/L1 catalyst system. A wide range of N2-aryl-1,2,3-triazoles were prepared from aryl bromides, chlorides and triflates with excellent (95–99%) N2-selectivity. DFT calculations suggest that formation of N2-arylated 1,2,3-triazoles is favored kinetically. PMID:21853510

  19. Synthesis of Dibenzo[h,rst]pentaphenes and Dibenzo[fg,qr]pentacenes by the Chemoselective C-O Arylation of Dimethoxyanthraquinones.

    Science.gov (United States)

    Suzuki, Yusuke; Yamada, Kohei; Watanabe, Kentaro; Kochi, Takuya; Ie, Yutaka; Aso, Yoshio; Kakiuchi, Fumitoshi

    2017-07-21

    A convenient method for the syntheses of dibenzo[h,rst]pentaphenes and dibenzo[fg,qr]pentacenes via the ruthenium-catalyzed chemoselective C-O arylation of 1,4- and 1,5-dimethoxyanthraquinones is described. Dimethoxyanthraquinones reacted selectively with arylboronates at the ortho C-O bonds to give diarylation products. An efficient two-step procedure consisting of a Corey-Chaykofsky reaction and subsequent dehydrative aromatization afforded derivatives of dibenzo[h,rst]pentaphenes and dibenzo[fg,qr]pentacenes. Hole-transporting characteristics were observed for a device with a bottom-contact configuration that was fabricated from one of these polycyclic aromatic hydrocarbons.

  20. 2/DPPF-catalysed microwave-assisted cyanide-free synthesis of aryl ...

    Indian Academy of Sciences (India)

    This study reports microwave-assisted cyanide-free synthesis of aryl nitriles from aryl halides using palladium ... protocol for cyanation of aryl halides using potas- .... eReaction by conventional heating. Figure 2. Structure of ligands from L1–L5. Table 2. Influence of Lewis acids.a. No. Lewis acids (mmol). Yield 3a (%)b. 1.

  1. Decarboxylative Aminomethylation of Aryl- and Vinylsulfonates through Combined Nickel- and Photoredox-Catalyzed Cross-Coupling

    KAUST Repository

    Fan, Lulu

    2016-09-23

    A mild approach for the decarboxylative aminomethylation of aryl sulfonates by the combination of photoredox and nickel catalysis through C−O bond cleavage is described for the first time. A wide range of aryl triflates as well as aryl mesylates, tosylates and alkenyl triflates afford the corresponding products in good to excellent yields.

  2. Hydrocarbons as food contaminants:

    OpenAIRE

    Lommatzsch, Martin

    2018-01-01

    The contamination of foods with hydrocarbon mixtures migrating from food contact materials (FCM) was first observed for jute and sisal bags treated with batching oil in the 1990s. Since the millennium, the focus has shifted to printing inks and recycled cardboard packaging as most recognized sources for hydrocarbon contamination from FCM. Mineral oil containing printing inks can either release hydrocarbons directly from the printing of folding boxes into food or indirectly entering the recycl...

  3. Hydrocarbons and air pollution

    International Nuclear Information System (INIS)

    Herz, O.

    1992-01-01

    This paper shows the influence of hydrocarbons vapors, emitted by transports or by volatile solvents using, on air pollution. Hydrocarbons are the principal precursors of photochemical pollution. After a brief introduction on atmospheric chemistry and photochemical reactions, the author describes the french prevention program against hydrocarbons emissions. In the last chapter, informations on international or european community programs for photochemical pollution study are given. 5 figs., 10 tabs

  4. Palladium-catalysed arylation of sulfonamide stabilised enolates

    CSIR Research Space (South Africa)

    Zeevaart, JG

    2005-03-07

    Full Text Available of an arylation reaction is found where the nucleophile is a sulfonamide.8 However, the success of this procedure required an enhancement of the acidity of the subject sulfonamide through the gener- ation of a b-cyanosulfonamide. The relatively acidic 2-[N... liquid ammonia chemistry.9 The preparation of compounds such as 1, containing both a sulfonamide and a cyano substituent to enhance the acidity of the protons between both functional groups, is relatively cumbersome. In cases where the a- aryl...

  5. Aryl Hydrocarbon Receptor Negatively Regulates Expression of the Plakoglobin Gene (Jup)

    Czech Academy of Sciences Publication Activity Database

    Procházková, Jiřina; Kabátková, Markéta; Šmerdová, Lenka; Pachernik, J.; Sýkorová, D.; Kohoutek, J.; Šimečková, P.; Hrubá, E.; Kozubík, Alois; Machala, M.; Vondráček, Jan

    2013-01-01

    Roč. 134, č. 2 (2013), s. 258-270 ISSN 1096-6080 R&D Projects: GA ČR(CZ) GA524/09/1337; GA ČR(CZ) GD204/09/H058; GA MŠk(CZ) EE2.3.30.0030 Grant - others:GA ČR(CZ) GA301/09/1832 Institutional research plan: CEZ:AV0Z50040702 Institutional support: RVO:68081707 Keywords : EMBRYONIC STEM-CELLS * LIVER EPITHELIAL-CELLS * AH RECEPTOR Subject RIV: BO - Biophysics Impact factor: 4.478, year: 2013

  6. Aryl hydrocarbon receptor ligand effects in RBL2H3 cells

    DEFF Research Database (Denmark)

    Maaetoft-Udsen, Kristina; Shimoda, Lori M. N.; Frøkiær, Hanne

    2012-01-01

    responses and release a spectrum of pro-inflammatory mediators including histamine, mast cell proteases, and pro-inflammatory cytokines such as IL-6 upon stimulation. The aim was to investigate the AHR in model mast cells and examine how both putative and known AHR ligands, e.g., kynurenine, kynurenic acid...... (KA), Resveratrol, indolmycin, and violacein, affect mast cell activation and signaling. These ligands were tested on calcium signaling, degranulation, and gene expression. The data show that AHR is present in three model mast cell lines, and that various known and putative AHR ligands regulate gene...

  7. Effect of silymarin flavonolignans and synthetic silybin derivatives on estrogen and aryl hydrocarbon receptor activation

    Czech Academy of Sciences Publication Activity Database

    Plíšková, M.; Vondráček, Jan; Křen, Vladimír; Gažák, Radek; Sedmera, Petr; Walterová, D.; Psotová, J.; Šimánek, V.; Machala, M.

    2005-01-01

    Roč. 215, 1-2 (2005), s. 80-89 ISSN 0300-483X R&D Projects: GA ČR(CZ) GA303/02/1097 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50200510 Keywords : estrogenicity * dioxin-like activity * silybin derivatives Subject RIV: BO - Biophysics Impact factor: 2.584, year: 2005

  8. No evidence of somatic aryl hydrocarbon receptor interacting protein mutations in sporadic endocrine neoplasia

    DEFF Research Database (Denmark)

    Raitila, A; Georgitsi, M; Karhu, A

    2007-01-01

    . Here, we have analyzed 32 pituitary adenomas and 79 other tumors of the endocrine system for somatic AIP mutations by direct sequencing. No somatic mutations were identified. However, two out of nine patients with prolactin-producing adenoma were shown to harbor a Finnish founder mutation (Q14X...... as non-secreting pituitary adenomas have been reported, most mutation-positive patients have had growth hormone-producing adenomas diagnosed at relatively young age. Pituitary adenomas are also component tumors of some familial endocrine neoplasia syndromes such as multiple endocrine neoplasia type 1...... (MEN1) and Carney complex (CNC). Genes underlying MEN1 and CNC are rarely mutated in sporadic pituitary adenomas, but more often in other lesions contributing to these two syndromes. Thus far, the occurrence of somatic AIP mutations has not been studied in endocrine tumors other than pituitary adenomas...

  9. Aryl hydrocarbon receptor 2 mediates the toxicity of Paclobutrazol on the digestive system of zebrafish embryos.

    Science.gov (United States)

    Wang, Wen-Der; Chen, Guan-Ting; Hsu, Hwei-Jan; Wu, Chang-Yi

    2015-02-01

    Paclobutrazol (PBZ), a trazole-containing fungicide and plant growth retardant, has been widely used for over 30 years to regulate plant growth and promote early fruit setting. Long-term usage of PBZ in agriculture and natural environments has resulted in residual PBZ in the soil and water. Chronic exposure to waterborne PBZ can cause various physiological effects in fish, including hepatic steatosis, antioxidant activity, and disruption of spermatogenesis. We have previously shown that PBZ also affects the rates of zebrafish embryonic survival and hatching, and causes developmental failure of the head skeleton and eyes; here, we further show that PBZ has embryonic toxic effects on digestive organs of zebrafish, and describe the underlying mechanisms. PBZ treatment of embryos resulted in dose-dependent morphological and functional abnormalities of the digestive organs. Real-time RT-PCR and in situ hybridization were used to show that PBZ strongly induces cyp1a1 expression in the digestive system, and slightly induces ahr2 expression in zebrafish embryos. Knockdown of ahr2 with morpholino oligonucleotides prevents PBZ toxicity. Thus, the toxic effect of PBZ on digestive organs is mediated by AhR2, as was previously reported for retene and TCDD. These findings have implications for understanding the potential toxicity of PBZ during embryogenesis, and thus the potential impact of fungicides on public health and the environment. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Interactions of the aryl hydrocarbon receptor with inflammatory mediators: Beyond CYP1A regulation

    Czech Academy of Sciences Publication Activity Database

    Vondráček, Jan; Umannová, Lenka; Machala, M.

    2011-01-01

    Roč. 12, č. 2 (2011), s. 89-103 ISSN 1389-2002 R&D Projects: GA ČR(CZ) GAP503/11/1227 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : AhR * proinflammatory cytokines * antiinflammatory drugs Subject RIV: BO - Biophysics Impact factor: 5.113, year: 2011

  11. The aryl hydrocarbon receptor is a modulator of anti-viral immunity

    Science.gov (United States)

    Head, Jennifer L.; Lawrence, B. Paige

    2009-01-01

    Although immune modulation by AhR ligands has been studied for many years, the impact of AhR activation on host defenses against viral infection has not, until recently, garnered much attention. The development of novel reagents and model systems, new information regarding antiviral immunity, and a growing appreciation for the global health threat posed by viruses have invigorated interest in understanding how environmental signals affect susceptibility to and pathological consequences of viral infection. Using influenza A virus as a model of respiratory viral infection, recent studies show that AhR activation cues signaling events in both leukocytes and non-immune cells. Functional alterations include suppressed lymphocyte responses and increased inflammation in the infected lung. AhR-mediated events within and extrinsic to hematopoietic cells has been investigated using bone marrow chimeras, which show that AhR alters different elements of the immune response by affecting different tissue targets. In particular, suppressed CD8+ T cell responses are due to deregulated events within leukocytes themselves, whereas increased neutrophil recruitment to and IFN-γ levels in the lung result from AhR-regulated events extrinsic to bone marrow-derived cells. This latter discovery suggests that epithelial and endothelial cells are overlooked targets of AhR-mediated changes in immune function. Further support that AhR influences host cell responses to viral infection are provided by several studies demonstrating that AhR interacts directly with viral proteins and affects viral latency. While AhR clearly modulates host responses to viral infection, we still have much to understand about the complex interactions between immune cells, viruses, and the host environment. PMID:19027719

  12. Comparative Analyses of Aryl Hydrocarbon Receptor Structure, Function, and Evolution in Marine Mammals

    Science.gov (United States)

    2007-02-01

    to assess biological parameters in large whales. Sloughed skin and fecal samples have been used with success; however, the utility of such samples is...applying our approach to fecal or sloughed skin samples . The minimally invasive nature of remote live biopsy is justified for gaining access to the...stable- isotope analyses of biopsy samples . Canadian Journal of Zoology 79:1442-1454. Hunt, K.E., R.M. Rolland, S.D. Kraus and S.K. Wasser. 2006. Analysis

  13. Efficient synthesis of 3H-indoles enabled by the lead-mediated α-arylation of β-ketoesters or γ-lactams using aryl azides.

    Science.gov (United States)

    Zhou, Fei; Driver, Tom G

    2014-06-06

    The development of a lead-mediated α-arylation reaction between aryl azides and β-ketoesters or γ-lactams that facilitates the formation of 3H-indoles is disclosed. Twenty-five examples are included which demonstrate the generality of this reaction to access aryl azides bearing tetrasubstituted o-alkyl substituents. When paired with a Staudinger reduction, this reaction streamlines the synthesis of functionalized 3H-indoles.

  14. Plant hydrocarbon recovery process

    Energy Technology Data Exchange (ETDEWEB)

    Dzadzic, P.M.; Price, M.C.; Shih, C.J.; Weil, T.A.

    1982-01-26

    A process for production and recovery of hydrocarbons from hydrocarbon-containing whole plants in a form suitable for use as chemical feedstocks or as hydrocarbon energy sources which process comprises: (A) pulverizing by grinding or chopping hydrocarbon-containing whole plants selected from the group consisting of euphorbiaceae, apocynaceae, asclepiadaceae, compositae, cactaceae and pinaceae families to a suitable particle size, (B) drying and preheating said particles in a reducing atmosphere under positive pressure (C) passing said particles through a thermal conversion zone containing a reducing atmosphere and with a residence time of 1 second to about 30 minutes at a temperature within the range of from about 200* C. To about 1000* C., (D) separately recovering the condensable vapors as liquids and the noncondensable gases in a condition suitable for use as chemical feedstocks or as hydrocarbon fuels.

  15. Synthesis of 4-Aryl Isoquinolinedione Derivatives by a Palladium-Catalyzed Coupling Reaction of Aryl Halides with Isoquinoline-1,3(2H,4H)-diones.

    Science.gov (United States)

    Yang, Yuanyong; Li, Yingxian; Cheng, Cheng; Yang, Guo; Zhang, Jiquan; Zhang, Yi; Zhao, Yonglong; Zhang, Lin; Li, Chun; Tang, Lei

    2018-02-23

    The palladium-catalyzed cross-coupling reaction of aryl halides with isoquinoline-1,3(2H,4H)-diones for the synthesis of 4-aryl isoquinoline-1,3(2H,4H)-diones was developed. The reaction conditions exhibit remarkable compatibility with various aryl halides and isoquinoline-1,3(2H,4H)-diones, and the product could be conveniently transformed to 4-aryl tetrahydroisoquinolines. (±) Dichlorofensine was synthesized using this protocol in two steps with an overall yield of 71%.

  16. C–H Bonds as Ubiquitous Functionality: Preparation of Multiple Regioisomers of Arylated 1,2,4-Triazoles via C–H Arylation

    Science.gov (United States)

    Joo, Jung Min; Guo, Pengfei

    2013-01-01

    We describe a general approach for the synthesis of complex aryl 1,2,4-triazoles. The electronic character of the C–H bonds and the triazole ring allows for the regioselective C–H arylation of 1-alkyl and 4-alkyl triazoles under catalytic conditions. We have also developed the SEM- and THP-switch as well as trans-N-alkylation, which enable sequential arylation of the triazole ring to prepare 3,5-diaryltriazoles. This straightforward strategy provides rapid access to a variety of arylated 1,2,4-triazoles and well complements existing cyclization methods. PMID:23276283

  17. Plasma devices for hydrocarbon reformation

    KAUST Repository

    Cha, Min Suk

    2017-02-16

    Plasma devices for hydrocarbon reformation are provided. Methods of using the devices for hydrocarbon reformation are also provided. The devices can include a liquid container to receive a hydrocarbon source, and a plasma torch configured to be submerged in the liquid. The plasma plume from the plasma torch can cause reformation of the hydrocarbon. The device can use a variety of plasma torches that can be arranged in a variety of positions in the liquid container. The devices can be used for the reformation of gaseous hydrocarbons and/or liquid hydrocarbons. The reformation can produce methane, lower hydrocarbons, higher hydrocarbons, hydrogen gas, water, carbon dioxide, carbon monoxide, or a combination thereof.

  18. Cyclohexenones Through Addition of Ethyl Acetoacetate to 3-Aryl-1 ...

    African Journals Online (AJOL)

    Chalcone derivatives 3a–i containing a thiophene ring were prepared by the condensation of 1-(thiophen-3-yl)ethanone with aromatic aldehydes in excellent yields. The Michael addition of ethyl acetoacetate 4 to chalcone derivatives 3a–i resulted in the formation of nine novel ethyl 6-aryl ...

  19. Regio- and Stereoselective a-Halogenation of 2-Aryl-1 ...

    African Journals Online (AJOL)

    ... 2-aryl-3-bromo-1-methylsulfonyl-2,3-dihydroquinolin-4(1H)-ones using iodine in methanol and pyridinium perbromide in acetic acid, respectively. The reactions were found to be regioselective and stereoselective by 1H NMR spectroscopy, affording in all cases the 2,3-trans isomers. X-ray crystallography was also used to ...

  20. Dithiocarbamate promoted practical synthesis of N-Aryl-2 ...

    Indian Academy of Sciences (India)

    a wide variety of disorders such as HIV,1 neuro degeneration2 and inflammatory diseases.3 Moreover,. 2-aminobenzoxazoles have also been reported as ..... and o-aminophenol/o-aminothiophenol and the results are listed in table 1. Several dithiocarbamates under- went the above conversion to form a series of N-aryl-.

  1. Molecular modelling studies on 2-amino 6-aryl ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Chemical Sciences; Volume 119; Issue 6. Molecular modelling studies on 2-amino 6-aryl-sulphonylbenzonitriles as non-nucleoside reverse transcriptase inhibitors of HIV-1: A QSPR approach. Nitin S Sapre Nilanjana Pancholi Swagata Gupta Arun Sikrwar Neelima Sapre. Volume 119 Issue 6 ...

  2. Characterization of hydrocarbon utilizing fungi from hydrocarbon ...

    African Journals Online (AJOL)

    Sediments from four different hydrocarbon polluted sites in Ogala-Bonny, Rivers State Nigeria and water samples from effluent discharge points of four different flow stations in Delta State were sampled. They were analyzed for presence of indigenous fungi. This was to establish possible fungal involvement in ...

  3. Continuous flow enantioselective arylation of aldehydes with ArZnEt using triarylboroxins as the ultimate source of aryl groups

    Directory of Open Access Journals (Sweden)

    Julien Rolland

    2009-10-01

    Full Text Available A continuous flow system for the synthesis of enantioenriched diarylmethanols from aldehydes is described. The system uses an amino alcohol-functionalized polystyrene resin as the catalyst, and the arylating agent is conveniently prepared by transmetallation of triarylboroxins with diethylzinc.

  4. Hydrocarbon toxicity: A review.

    Science.gov (United States)

    Tormoehlen, L M; Tekulve, K J; Nañagas, K A

    2014-06-01

    Clinical effects of hydrocarbon exposure have been reported since 1897. These substances are ubiquitous, and their exposures are common. The specific hydrocarbon and route of exposure will determine the clinical effect, and an understanding of this is helpful in the care of the hydrocarbon-exposed patient. To complete a comprehensive review of the literature on hydrocarbon toxicity and summarize the findings. Relevant literature was identified through searches of Medline (PubMed/OVID) and Cochrane Library databases (inclusive of years 1975-2013), as well as from multiple toxicology textbooks. Bibliographies of the identified articles were also reviewed. Search terms included combinations of the following: hydrocarbons, inhalants, encephalopathy, coma, cognitive deficits, inhalant abuse, huffing, sudden sniffing death, toluene, renal tubular acidosis, metabolic acidosis, arrhythmia, dermatitis, and aspiration pneumonitis. All pertinent clinical trials, observational studies, and case reports relevant to hydrocarbon exposure and published in English were reviewed. Chronic, occupational hydrocarbon toxicity was not included. Exposure to hydrocarbons occurs through one of the following routes: inhalation, ingestion with or without aspiration, or dermal exposure. Inhalational abuse is associated with central nervous system depression, metabolic acidosis, and arrhythmia. The exact mechanism of the CNS depression is unknown, but experimental evidence suggests effects on NMDA, dopamine, and GABA receptors. Chronic toluene inhalation causes a non-anion gap metabolic acidosis associated with hypokalemia. Halogenated hydrocarbon abuse can cause a fatal malignant arrhythmia, termed "sudden sniffing death". Individuals who regularly abuse hydrocarbons are more likely to be polysubstance users, exhibit criminal or violent behavior, and develop memory and other cognitive deficits. Heavy, long-term use results in cerebellar dysfunction, encephalopathy, weakness, and dementia

  5. Trigger Finger (Stenosing Tenosynovitis)

    Science.gov (United States)

    ... a friend * required fields From * To * DESCRIPTION Stenosing tenosynovitis is a condition commonly known as “trigger finger.” It is sometimes also called “trigger thumb.” The tendons that bend the fingers glide easily with ...

  6. Causality and headache triggers

    Science.gov (United States)

    Turner, Dana P.; Smitherman, Todd A.; Martin, Vincent T.; Penzien, Donald B.; Houle, Timothy T.

    2013-01-01

    Objective The objective of this study was to explore the conditions necessary to assign causal status to headache triggers. Background The term “headache trigger” is commonly used to label any stimulus that is assumed to cause headaches. However, the assumptions required for determining if a given stimulus in fact has a causal-type relationship in eliciting headaches have not been explicated. Methods A synthesis and application of Rubin’s Causal Model is applied to the context of headache causes. From this application the conditions necessary to infer that one event (trigger) causes another (headache) are outlined using basic assumptions and examples from relevant literature. Results Although many conditions must be satisfied for a causal attribution, three basic assumptions are identified for determining causality in headache triggers: 1) constancy of the sufferer; 2) constancy of the trigger effect; and 3) constancy of the trigger presentation. A valid evaluation of a potential trigger’s effect can only be undertaken once these three basic assumptions are satisfied during formal or informal studies of headache triggers. Conclusions Evaluating these assumptions is extremely difficult or infeasible in clinical practice, and satisfying them during natural experimentation is unlikely. Researchers, practitioners, and headache sufferers are encouraged to avoid natural experimentation to determine the causal effects of headache triggers. Instead, formal experimental designs or retrospective diary studies using advanced statistical modeling techniques provide the best approaches to satisfy the required assumptions and inform causal statements about headache triggers. PMID:23534872

  7. Triggering the GRANDE array

    International Nuclear Information System (INIS)

    Wilson, C.L.; Bratton, C.B.; Gurr, J.; Kropp, W.; Nelson, M.; Sobel, H.; Svoboda, R.; Yodh, G.; Burnett, T.; Chaloupka, V.; Wilkes, R.J.; Cherry, M.; Ellison, S.B.; Guzik, T.G.; Wefel, J.; Gaidos, J.; Loeffler, F.; Sembroski, G.; Goodman, J.; Haines, T.J.; Kielczewska, D.; Lane, C.; Steinberg, R.; Lieber, M.; Nagle, D.; Potter, M.; Tripp, R.

    1990-01-01

    A brief description of the Gamma Ray And Neutrino Detector Experiment (GRANDE) is presented. The detector elements and electronics are described. The trigger logic for the array is then examined. The triggers for the Gamma Ray and the Neutrino portions of the array are treated separately. (orig.)

  8. Triggering trigeminal neuralgia

    DEFF Research Database (Denmark)

    Di Stefano, Giulia; Maarbjerg, Stine; Nurmikko, Turo

    2018-01-01

    Introduction Although it is widely accepted that facial pain paroxysms triggered by innocuous stimuli constitute a hallmark sign of trigeminal neuralgia, very few studies to date have systematically investigated the role of the triggers involved. In the recently published diagnostic classification...

  9. Reactivity of N-(omega-haloalkyl)-beta-lactams with regard to lithium aluminium hydride: novel synthesis of 1-(1-aryl-3-hydroxypropyl)aziridines and 3-aryl-3-(N-propylamino)propan-1-ols.

    Science.gov (United States)

    D'hooghe, Matthias; Dekeukeleire, Stijn; De Kimpe, Norbert

    2008-04-07

    The reactivity of 4-aryl-1-(2-chloroethyl)azetidin-2-ones and 4-aryl-1-(3-bromopropyl)azetidin-2-ones with regard to lithium aluminium hydride has been evaluated for the first time. 4-Aryl-1-(2-chloroethyl)azetidin-2-ones were transformed into novel 1-(1-aryl-3-hydroxypropyl)aziridines through an unprecedented conversion of beta-lactams into 2,3-unsubstituted aziridine derivatives. Unexpectedly, 4-aryl-1-(3-bromopropyl)azetidin-2-ones underwent dehalogenation towards 3-aryl-3-(N-propylamino)propan-1-ols upon treatment with LiAlH(4). 1-(1-Aryl-3-hydroxypropyl)aziridines were further elaborated by means of ring opening reactions using benzyl bromide in acetonitrile towards 3-aryl-3-[N-benzyl-N-(2-bromoethyl)amino]propan-1-ols and using aluminium(iii) chloride in diethyl ether, affording 3-aryl-3-[N-(2-chloroethyl)amino]propan-1-ols.

  10. Thraustochytrid protists degrade hydrocarbons

    Digital Repository Service at National Institute of Oceanography (India)

    Raikar, M.T.; Raghukumar, S.; Vani, V.; David, J.J.; Chandramohan, D.

    Although thraustochytrid protists are known to be of widespread occurrence in the sea, their hydrocarbon-degrading abilities have never been investigated. We isolated thraustochytrids from coastal waters and sediments of Goa coast by enriching MPN...

  11. Palladium-catalyzed microwave-assisted direct arylation of imidazo[2,1-b]thiazoles with aryl bromides: synthesis and mechanistic study.

    Science.gov (United States)

    Zhu, Yi-Shuo; Shi, Benyi; Fang, Ran; Wang, Xiaoxuan; Jing, Huanwang

    2014-08-14

    A palladium-catalyzed direct C-H arylation of various imidazo[2,1-b]thiazoles with a range of aryl bromides under microwave irradiation is described. 6-Phenyl substituted imidazo[2,1-b]thiazoles could be regioselectively C-5 arylated using the developed protocol. The utility of this method enables the representative coupling product to be achieved by a sequential one-pot reaction. Density functional theory (DFT) calculations show that this arylation proceeds via a concerted metalation-deprotonation (CMD) pathway, which is in agreement with our experimental results. This work provides a convenient access to a variety of biologically active imidazo[2,1-b]thiazole derivatives. Also, it enriches the mechanism study of site-selective C-H arylation in fused heterocycles, and offers a valuable guide to design highly efficient catalytic systems for the preparation of similar compounds.

  12. The ATLAS Trigger System

    CERN Document Server

    Hauser, R

    2004-01-01

    ATLAS is one of two general-purpose detectors at the next generation proton-proton collider, the LHC. The high rate of interactions and the large number of read-out channels make the trigger system for ATLAS a challenging task. The initial bunch crossing rate of 40~MHz has to be reduced to about 200 Hz while preserving the physics signals against a large background. ATLAS uses a three-level trigger system, with the first level implemented in custom hardware, while the high level trigger systems are implemented in software on commodity hardware. This note describes the physics motivation, the various selection strategies for different channels as well as the physical implementation of the trigger system.

  13. Calo trigger acquisition system

    CERN Multimedia

    Franchini, Matteo

    2016-01-01

    Calo trigger acquisition system - Evolution of the acquisition system from a multiple boards system (upper, orange cables) to a single board one (below, light blue cables) where all the channels are collected in a single board.

  14. Asthma Triggers: Gain Control

    Science.gov (United States)

    ... in your house and may trigger asthma. Your asthma or your child's asthma may be worse around products such as ... You Can Take If you find that your asthma or your child's asthma gets worse when you use a certain ...

  15. Calorimetry triggering in ATLAS

    CERN Document Server

    Igonkina, O; Adragna, P; Aharrouche, M; Alexandre, G; Andrei, V; Anduaga, X; Aracena, I; Backlund, S; Baines, J; Barnett, B M; Bauss, B; Bee, C; Behera, P; Bell, P; Bendel, M; Benslama, K; Berry, T; Bogaerts, A; Bohm, C; Bold, T; Booth, J R A; Bosman, M; Boyd, J; Bracinik, J; Brawn, I, P; Brelier, B; Brooks, W; Brunet, S; Bucci, F; Casadei, D; Casado, P; Cerri, A; Charlton, D G; Childers, J T; Collins, N J; Conde Muino, P; Coura Torres, R; Cranmer, K; Curtis, C J; Czyczula, Z; Dam, M; Damazio, D; Davis, A O; De Santo, A; Degenhardt, J; Delsart, P A; Demers, S; Demirkoz, B; Di Mattia, A; Diaz, M; Djilkibaev, R; Dobson, E; Dova, M, T; Dufour, M A; Eckweiler, S; Ehrenfeld, W; Eifert, T; Eisenhandler, E; Ellis, N; Emeliyanov, D; Enoque Ferreira de Lima, D; Faulkner, P J W; Ferland, J; Flacher, H; Fleckner, J E; Flowerdew, M; Fonseca-Martin, T; Fratina, S; Fhlisch, F; Gadomski, S; Gallacher, M P; Garitaonandia Elejabarrieta, H; Gee, C N P; George, S; Gillman, A R; Goncalo, R; Grabowska-Bold, I; Groll, M; Gringer, C; Hadley, D R; Haller, J; Hamilton, A; Hanke, P; Hauser, R; Hellman, S; Hidvgi, A; Hillier, S J; Hryn'ova, T; Idarraga, J; Johansen, M; Johns, K; Kalinowski, A; Khoriauli, G; Kirk, J; Klous, S; Kluge, E-E; Koeneke, K; Konoplich, R; Konstantinidis, N; Kwee, R; Landon, M; LeCompte, T; Ledroit, F; Lei, X; Lendermann, V; Lilley, J N; Losada, M; Maettig, S; Mahboubi, K; Mahout, G; Maltrana, D; Marino, C; Masik, J; Meier, K; Middleton, R P; Mincer, A; Moa, T; Monticelli, F; Moreno, D; Morris, J D; Mller, F; Navarro, G A; Negri, A; Nemethy, P; Neusiedl, A; Oltmann, B; Olvito, D; Osuna, C; Padilla, C; Panes, B; Parodi, F; Perera, V J O; Perez, E; Perez Reale, V; Petersen, B; Pinzon, G; Potter, C; Prieur, D P F; Prokishin, F; Qian, W; Quinonez, F; Rajagopalan, S; Reinsch, A; Rieke, S; Riu, I; Robertson, S; Rodriguez, D; Rogriquez, Y; Rhr, F; Saavedra, A; Sankey, D P C; Santamarina, C; Santamarina Rios, C; Scannicchio, D; Schiavi, C; Schmitt, K; Schultz-Coulon, H C; Schfer, U; Segura, E; Silverstein, D; Silverstein, S; Sivoklokov, S; Sjlin, J; Staley, R J; Stamen, R; Stelzer, J; Stockton, M C; Straessner, A; Strom, D; Sushkov, S; Sutton, M; Tamsett, M; Tan, C L A; Tapprogge, S; Thomas, J P; Thompson, P D; Torrence, E; Tripiana, M; Urquijo, P; Urrejola, P; Vachon, B; Vercesi, V; Vorwerk, V; Wang, M; Watkins, P M; Watson, A; Weber, P; Weidberg, T; Werner, P; Wessels, M; Wheeler-Ellis, S; Whiteson, D; Wiedenmann, W; Wielers, M; Wildt, M; Winklmeier, F; Wu, X; Xella, S; Zhao, L; Zobernig, H; de Seixas, J M; dos Anjos, A; Asman, B; Özcan, E

    2009-01-01

    The ATLAS experiment is preparing for data taking at 14 TeV collision energy. A rich discovery physics program is being prepared in addition to the detailed study of Standard Model processes which will be produced in abundance. The ATLAS multi-level trigger system is designed to accept one event in 2 105 to enable the selection of rare and unusual physics events. The ATLAS calorimeter system is a precise instrument, which includes liquid Argon electro-magnetic and hadronic components as well as a scintillator-tile hadronic calorimeter. All these components are used in the various levels of the trigger system. A wide physics coverage is ensured by inclusively selecting events with candidate electrons, photons, taus, jets or those with large missing transverse energy. The commissioning of the trigger system is being performed with cosmic ray events and by replaying simulated Monte Carlo events through the trigger and data acquisition system.

  16. The ATLAS Trigger System

    CERN Document Server

    Owen, Rhys Edward; The ATLAS collaboration

    2018-01-01

    The ATLAS experiment employs a complex trigger system to enable the collaborations physics program. The LHC is now well in to its second running period delivering proton proton collisions at $\\sqrt{s}=13$ TeV with high instantaneous luminosity. This talk will describe the two level hardware and software trigger used to select events in this environment including recent improvements and the latest performance results.

  17. 2017 Tau Trigger Efficiencies

    CERN Document Server

    CMS Collaboration

    2018-01-01

    Triggers selecting events with hadronically decaying $\\tau$ leptons ($\\tau_h$) are used in a wide variety of CMS analyses, in particular those targeting processes with a $H \\rightarrow \\tau\\tau$ decay. The performance of the $\\tau_h$ triggers is presented for data collected in 2017, corresponding to an integrated luminosity of 41.5\\,fb$^{-1}$ at 13 TeV, and compared with simulation.

  18. Room-temperature Cu-catalyzed N-arylation of aliphatic amines in neat water.

    Science.gov (United States)

    Wang, Deping; Zheng, Yanwen; Yang, Min; Zhang, Fuxing; Mao, Fangfang; Yu, Jiangxi; Xia, Xiaohong

    2017-10-04

    A room-temperature and PTC-free copper-catalyzed N-arylation of aliphatic amines in neat water has been developed. Using a combination of CuI and 6,7-dihydroquinolin-8(5H)-one oxime as the catalyst and KOH as the base, a wide range of aliphatic amines are arylated with various aryl and heteroaryl halides to give the corresponding products in up to 95% yield.

  19. Diversification of indoles via microwave-assisted ligand-free copper-catalyzed N-arylation

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Jae Kwan; Lee, Jin Hee; Kim, Tae Sung; Yum, Eul Kgun [Dept. of Chemistry, Chu ngnam National University, Daejon (Korea, Republic of); Park, Jee Jung [Western Seoul Center Korea Basic Science Institute, Seoul (Korea, Republic of)

    2016-12-15

    A simple, efficient Cu{sub 2}O catalyst system under microwave irradiation was developed for N-arylation of various indoles without ligands and additives. Diverse N-heteroarylated indoles were prepared by coupling indoles with various heteroaryl halides within 1 h. The selective reactivity of bromoindole with aryl iodide provided N-aryl bromoindoles, which could be useful intermediates for palladium-catalyzed Heck and Suzuki coupling reactions.

  20. Design and synthesis of aryl ether and sulfone hydroxamic acids as potent histone deacetylase (HDAC) inhibitors.

    Science.gov (United States)

    Pabba, Chittari; Gregg, Brian T; Kitchen, Douglas B; Chen, Zhen Jia; Judkins, Angela

    2011-01-01

    A series of novel hydroxamic acid based histone deacetylases (HDAC) inhibitors with aryl ether and aryl sulfone residues at the terminus of a substituted, unsaturated 5-carbon spacer moiety have been synthesized for the first time and evaluated. Compounds with meta- and para-substitution on the aryl ring of ether hydroxamic acids 19c, 20c, 19e, 19f and 19g are potent HDAC inhibitors with activities at low nanomolar levels. Copyright © 2010 Elsevier Ltd. All rights reserved.

  1. LHCb Topological Trigger Reoptimization

    CERN Document Server

    INSPIRE-00400931; Ilten, Philip; Khairullin, Egor; Rogozhnikov, Alex; Ustyuzhanin, Andrey; Williams, Michael

    2015-12-23

    The main b-physics trigger algorithm used by the LHCb experiment is the so-called topological trigger. The topological trigger selects vertices which are a) detached from the primary proton-proton collision and b) compatible with coming from the decay of a b-hadron. In the LHC Run 1, this trigger, which utilized a custom boosted decision tree algorithm, selected a nearly 100% pure sample of b-hadrons with a typical efficiency of 60-70%; its output was used in about 60% of LHCb papers. This talk presents studies carried out to optimize the topological trigger for LHC Run 2. In particular, we have carried out a detailed comparison of various machine learning classifier algorithms, e.g., AdaBoost, MatrixNet and neural networks. The topological trigger algorithm is designed to select all "interesting" decays of b-hadrons, but cannot be trained on every such decay. Studies have therefore been performed to determine how to optimize the performance of the classification algorithm on decays not used in the training. ...

  2. Topological Trigger Developments

    CERN Multimedia

    Likhomanenko, Tatiana

    2015-01-01

    The main b-physics trigger algorithm used by the LHCb experiment is the so-called topological trigger. The topological trigger selects vertices which are a) detached from the primary proton-proton collision and b) compatible with coming from the decay of a b-hadron. In the LHC Run 1, this trigger utilized a custom boosted decision tree algorithm, selected an almost 100% pure sample of b-hadrons with a typical efficiency of 60-70%, and its output was used in about 60% of LHCb papers. This talk presents studies carried out to optimize the topological trigger for LHC Run 2. In particular, we have carried out a detailed comparison of various machine learning classifier algorithms, e.g., AdaBoost, MatrixNet and uBoost. The topological trigger algorithm is designed to select all "interesting" decays of b-hadrons, but cannot be trained on every such decay. Studies have therefore been performed to determine how to optimize the performance of the classification algorithm on decays not used in the training. These inclu...

  3. Iron-Catalyzed Alkylations of Aryl Sulfamates and Carbamates

    Science.gov (United States)

    Silberstein, Amanda L.; Ramgren, Stephen D.; Garg, Neil K.

    2012-01-01

    The alkylation of aryl sulfamates and carbamates using iron catalysis is reported. The method constructs sp2–sp3 carbon–carbon bonds and provides synthetically useful yields across a range of substrates (>35 examples). The directing group ability of sulfamates and carbamates, accompanied by their low reactivity toward conventional cross-couplings, render these substrates useful for the synthesis of polyfunctionalized arenes. PMID:22758657

  4. Investigation into ramie whisker reinforced arylated soy protein composites

    CSIR Research Space (South Africa)

    Kumar, R

    2010-03-01

    Full Text Available Reinforced Arylated Soy Protein Composites Rakesh Kumar1,2*, Lina Zhang2 1CSIR MSM, Port Elizabeth 6000, South Africa 2Department of Chemistry, Wuhan University, Wuhan 430072, China Abstract Whiskers were prepared from ramie fibers and were... of synthetic fibers and matrices the reuse of classical fibers reinforced composites are not possible. To get rid from these types of composites we use landfill disposable systems. Due to increasing population, lots of nonbiodegradable wastes are generated...

  5. Arylation of Rhodium(II) Azavinyl Carbenes with Boronic Acids

    Science.gov (United States)

    Selander, Nicklas; Worrell, Brady T.; Chuprakov, Stepan; Velaparthi, Subash; Fokin, Valery V.

    2013-01-01

    A highly efficient and stereoselective arylation of in situ generated azavinyl carbenes affording 2,2-diaryl enamines at ambient temperatures has been developed. These transition metal carbenes are directly produced from readily available and stable 1-sulfonyl-1,2,3-triazoles in the presence of a rhodium carboxylate catalyst. In several cases, the enamines generated in this reaction can be cyclized into substituted indoles employing copper catalysts. PMID:22913576

  6. Palladium-Catalyzed α-Arylation of Benzylic Phosphine Oxides

    Science.gov (United States)

    Montel, Sonia; Jia, Tiezheng

    2014-01-01

    A novel approach to prepare diarylmethyl phosphine oxides from benzyl phosphine oxides via deprotonative cross-coupling processes (DCCP) is reported. The optimization of the reaction was guided by High-Throughput Experimentation (HTE) techniques. The Pd(OAc)2/Xantphos-based catalyst enabled the reaction between benzyl diphenyl or dicyclohexyl phosphine oxide derivatives and aryl bromides in good to excellent yields (51–91%). PMID:24295336

  7. Aryl-aldehyde formation in fungal polyketides: discovery and characterization of a distinct biosynthetic mechanism.

    Science.gov (United States)

    Wang, Meng; Beissner, Mirko; Zhao, Huimin

    2014-02-20

    Aryl-aldehydes are a common feature in fungal polyketides, which are considered to be exclusively generated by the R domain of nonreducing polyketide synthases (NR-PKSs). However, by cloning and heterologous expression of both cryptic NR-PKS and nonribosomal peptide synthase (NRPS)-like genes from Aspergillus terreus in Saccharomyces cerevisiae, we identified a distinct mechanism for aryl-aldehyde formation in which a NRPS-like protein activates and reduces an aryl-acid produced by the accompanying NR-PKS to an aryl-aldehyde. Bioinformatics study indicates that such a mechanism may be widely used throughout the fungi kingdom. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Dimerization of tri(4-bromophenyl)benzene by aryl-aryl coupling from solution on a gold surface.

    Science.gov (United States)

    Russell, James C; Blunt, Matthew O; Garfitt, Jason M; Scurr, David J; Alexander, Morgan; Champness, Neil R; Beton, Peter H

    2011-03-30

    Monolayers of monomer 1,3,5-tri(4-bromophenyl)benzene (TBPB) and the dimerized product 3,3''',5,5'''-tetra(4-bromophenyl)quaterphenyl (TBPQ) on a gold surface have been studied using ambient scanning tunneling microscopy and time-of-flight secondary ion mass spectrometry (ToF-SIMS). Molecular layers are prepared by allowing sessile drops of solution to dry on a gold substrate. For room-temperature deposition we observe ordered arrays of TBPB in three distinct packing arrangements. Deposition on a heated substrate leads to the formation of the dimerized product, TBPQ, through a surface-induced aryl-aryl coupling. Regions of TBPQ coexist with regions of disordered multiply linked molecules. The conversion of monomer TPBP to dimers is confirmed using ToF-SIMS. Our results demonstrate an alternative, solution-phase approach to the formation of large molecules and nanostructures by coupling reactions.

  9. CMS Trigger Performance

    CERN Document Server

    Donato, Silvio

    2017-01-01

    During its second run of operation (Run 2) which started in 2015, the LHC will deliver a peak instantaneous luminosity that may reach $2 \\cdot 10^{34}$ cm$^{-2}$s$^{-1}$ with an average pile-up of about 55, far larger than the design value. Under these conditions, the online event selection is a very challenging task. In CMS, it is realized by a two-level trigger system the Level-1 (L1) Trigger, implemented in custom-designed electronics, and the High Level Trigger (HLT), a streamlined version of the offline reconstruction software running on a computer farm. In order to face this challenge, the L1 trigger has been through a major upgrade compared to Run 1, whereby all electronic boards of the system have been replaced, allowing more sophisticated algorithms to be run online. Its last stage, the global trigger, is now able to perform complex selections and to compute high-level quantities, like invariant masses. Likewise, the algorithms that run in the HLT go through big improvements; in particular, new appr...

  10. The CMS trigger system

    CERN Document Server

    Khachatryan, Vardan; Tumasyan, Armen; Adam, Wolfgang; Aşılar, Ece; Bergauer, Thomas; Brandstetter, Johannes; Brondolin, Erica; Dragicevic, Marko; Erö, Janos; Flechl, Martin; Friedl, Markus; Fruehwirth, Rudolf; Ghete, Vasile Mihai; Hartl, Christian; Hörmann, Natascha; Hrubec, Josef; Jeitler, Manfred; Knünz, Valentin; König, Axel; Krammer, Manfred; Krätschmer, Ilse; Liko, Dietrich; Matsushita, Takashi; Mikulec, Ivan; Rabady, Dinyar; Rahbaran, Babak; Rohringer, Herbert; Schieck, Jochen; Schöfbeck, Robert; Strauss, Josef; Treberer-Treberspurg, Wolfgang; Waltenberger, Wolfgang; Wulz, Claudia-Elisabeth; Mossolov, Vladimir; Shumeiko, Nikolai; Suarez Gonzalez, Juan; Alderweireldt, Sara; Cornelis, Tom; De Wolf, Eddi A; Janssen, Xavier; Knutsson, Albert; Lauwers, Jasper; Luyckx, Sten; Van De Klundert, Merijn; Van Haevermaet, Hans; Van Mechelen, Pierre; Van Remortel, Nick; Van Spilbeeck, Alex; Abu Zeid, Shimaa; Blekman, Freya; D'Hondt, Jorgen; Daci, Nadir; De Bruyn, Isabelle; Deroover, Kevin; Heracleous, Natalie; Keaveney, James; Lowette, Steven; Moreels, Lieselotte; Olbrechts, Annik; Python, Quentin; Strom, Derek; Tavernier, Stefaan; Van Doninck, Walter; Van Mulders, Petra; Van Onsem, Gerrit Patrick; Van Parijs, Isis; Barria, Patrizia; Brun, Hugues; Caillol, Cécile; Clerbaux, Barbara; De Lentdecker, Gilles; Fasanella, Giuseppe; Favart, Laurent; Grebenyuk, Anastasia; Karapostoli, Georgia; Lenzi, Thomas; Léonard, Alexandre; Maerschalk, Thierry; Marinov, Andrey; Perniè, Luca; Randle-conde, Aidan; Reis, Thomas; Seva, Tomislav; Vander Velde, Catherine; Vanlaer, Pascal; Yonamine, Ryo; Zenoni, Florian; Zhang, Fengwangdong; Beernaert, Kelly; Benucci, Leonardo; Cimmino, Anna; Crucy, Shannon; Dobur, Didar; Fagot, Alexis; Garcia, Guillaume; Gul, Muhammad; Mccartin, Joseph; Ocampo Rios, Alberto Andres; Poyraz, Deniz; Ryckbosch, Dirk; Salva Diblen, Sinem; Sigamani, Michael; Strobbe, Nadja; Tytgat, Michael; Van Driessche, Ward; Yazgan, Efe; Zaganidis, Nicolas; Basegmez, Suzan; Beluffi, Camille; Bondu, Olivier; Brochet, Sébastien; Bruno, Giacomo; Caudron, Adrien; Ceard, Ludivine; Da Silveira, Gustavo Gil; Delaere, Christophe; Favart, Denis; Forthomme, Laurent; Giammanco, Andrea; Hollar, Jonathan; Jafari, Abideh; Jez, Pavel; Komm, Matthias; Lemaitre, Vincent; Mertens, Alexandre; Musich, Marco; Nuttens, Claude; Perrini, Lucia; Pin, Arnaud; Piotrzkowski, Krzysztof; Popov, Andrey; Quertenmont, Loic; Selvaggi, Michele; Vidal Marono, Miguel; Beliy, Nikita; Hammad, Gregory Habib; Aldá Júnior, Walter Luiz; Alves, Fábio Lúcio; Alves, Gilvan; Brito, Lucas; Correa Martins Junior, Marcos; Hamer, Matthias; Hensel, Carsten; Mora Herrera, Clemencia; Moraes, Arthur; Pol, Maria Elena; Rebello Teles, Patricia; Belchior Batista Das Chagas, Ewerton; Carvalho, Wagner; Chinellato, Jose; Custódio, Analu; Melo Da Costa, Eliza; De Jesus Damiao, Dilson; De Oliveira Martins, Carley; Fonseca De Souza, Sandro; Huertas Guativa, Lina Milena; Malbouisson, Helena; Matos Figueiredo, Diego; Mundim, Luiz; Nogima, Helio; Prado Da Silva, Wanda Lucia; Santoro, Alberto; Sznajder, Andre; Tonelli Manganote, Edmilson José; Vilela Pereira, Antonio; Ahuja, Sudha; Bernardes, Cesar Augusto; De Souza Santos, Angelo; Dogra, Sunil; Tomei, Thiago; De Moraes Gregores, Eduardo; Mercadante, Pedro G; Moon, Chang-Seong; Novaes, Sergio F; Padula, Sandra; Romero Abad, David; Ruiz Vargas, José Cupertino; Aleksandrov, Aleksandar; Hadjiiska, Roumyana; Iaydjiev, Plamen; Rodozov, Mircho; Stoykova, Stefka; Sultanov, Georgi; Vutova, Mariana; Dimitrov, Anton; Glushkov, Ivan; Litov, Leander; Pavlov, Borislav; Petkov, Peicho; Ahmad, Muhammad; Bian, Jian-Guo; Chen, Guo-Ming; Chen, He-Sheng; Chen, Mingshui; Cheng, Tongguang; Du, Ran; Jiang, Chun-Hua; Plestina, Roko; Romeo, Francesco; Shaheen, Sarmad Masood; Spiezia, Aniello; Tao, Junquan; Wang, Chunjie; Wang, Zheng; Zhang, Huaqiao; Asawatangtrakuldee, Chayanit; Ban, Yong; Li, Qiang; Liu, Shuai; Mao, Yajun; Qian, Si-Jin; Wang, Dayong; Xu, Zijun; Avila, Carlos; Cabrera, Andrés; Chaparro Sierra, Luisa Fernanda; Florez, Carlos; Gomez, Juan Pablo; Gomez Moreno, Bernardo; Sanabria, Juan Carlos; Godinovic, Nikola; Lelas, Damir; Puljak, Ivica; Ribeiro Cipriano, Pedro M; Antunovic, Zeljko; Kovac, Marko; Brigljevic, Vuko; Kadija, Kreso; Luetic, Jelena; Micanovic, Sasa; Sudic, Lucija; Attikis, Alexandros; Mavromanolakis, Georgios; Mousa, Jehad; Nicolaou, Charalambos; Ptochos, Fotios; Razis, Panos A; Rykaczewski, Hans; Bodlak, Martin; Finger, Miroslav; Finger Jr, Michael; Assran, Yasser; El Sawy, Mai; Elgammal, Sherif; Ellithi Kamel, Ali; Mahmoud, Mohammed; Calpas, Betty; Kadastik, Mario; Murumaa, Marion; Raidal, Martti; Tiko, Andres; Veelken, Christian; Eerola, Paula; Pekkanen, Juska; Voutilainen, Mikko; Härkönen, Jaakko; Karimäki, Veikko; Kinnunen, Ritva; Lampén, Tapio; Lassila-Perini, Kati; Lehti, Sami; Lindén, Tomas; Luukka, Panja-Riina; Mäenpää, Teppo; Peltola, Timo; Tuominen, Eija; Tuominiemi, Jorma; Tuovinen, Esa; Wendland, Lauri; Talvitie, Joonas; Tuuva, Tuure; Besancon, Marc; Couderc, Fabrice; Dejardin, Marc; Denegri, Daniel; Fabbro, Bernard; Faure, Jean-Louis; Favaro, Carlotta; Ferri, Federico; Ganjour, Serguei; Givernaud, Alain; Gras, Philippe; Hamel de Monchenault, Gautier; Jarry, Patrick; Locci, Elizabeth; Machet, Martina; Malcles, Julie; Rander, John; Rosowsky, André; Titov, Maksym; Zghiche, Amina; Antropov, Iurii; Baffioni, Stephanie; Beaudette, Florian; Busson, Philippe; Cadamuro, Luca; Chapon, Emilien; Charlot, Claude; Dahms, Torsten; Davignon, Olivier; Filipovic, Nicolas; Florent, Alice; Granier de Cassagnac, Raphael; Lisniak, Stanislav; Mastrolorenzo, Luca; Miné, Philippe; Naranjo, Ivo Nicolas; Nguyen, Matthew; Ochando, Christophe; Ortona, Giacomo; Paganini, Pascal; Pigard, Philipp; Regnard, Simon; Salerno, Roberto; Sauvan, Jean-Baptiste; Sirois, Yves; Strebler, Thomas; Yilmaz, Yetkin; Zabi, Alexandre; Agram, Jean-Laurent; Andrea, Jeremy; Aubin, Alexandre; Bloch, Daniel; Brom, Jean-Marie; Buttignol, Michael; Chabert, Eric Christian; Chanon, Nicolas; Collard, Caroline; Conte, Eric; Coubez, Xavier; Fontaine, Jean-Charles; Gelé, Denis; Goerlach, Ulrich; Goetzmann, Christophe; Le Bihan, Anne-Catherine; Merlin, Jeremie Alexandre; Skovpen, Kirill; Van Hove, Pierre; Gadrat, Sébastien; Beauceron, Stephanie; Bernet, Colin; Boudoul, Gaelle; Bouvier, Elvire; Carrillo Montoya, Camilo Andres; Chierici, Roberto; Contardo, Didier; Courbon, Benoit; Depasse, Pierre; El Mamouni, Houmani; Fan, Jiawei; Fay, Jean; Gascon, Susan; Gouzevitch, Maxime; Ille, Bernard; Lagarde, Francois; Laktineh, Imad Baptiste; Lethuillier, Morgan; Mirabito, Laurent; Pequegnot, Anne-Laure; Perries, Stephane; Ruiz Alvarez, José David; Sabes, David; Sgandurra, Louis; Sordini, Viola; Vander Donckt, Muriel; Verdier, Patrice; Viret, Sébastien; Toriashvili, Tengizi; Tsamalaidze, Zviad; Autermann, Christian; Beranek, Sarah; Edelhoff, Matthias; Feld, Lutz; Heister, Arno; Kiesel, Maximilian Knut; Klein, Katja; Lipinski, Martin; Ostapchuk, Andrey; Preuten, Marius; Raupach, Frank; Schael, Stefan; Schulte, Jan-Frederik; Verlage, Tobias; Weber, Hendrik; Wittmer, Bruno; Zhukov, Valery; Ata, Metin; Brodski, Michael; Dietz-Laursonn, Erik; Duchardt, Deborah; Endres, Matthias; Erdmann, Martin; Erdweg, Sören; Esch, Thomas; Fischer, Robert; Güth, Andreas; Hebbeker, Thomas; Heidemann, Carsten; Hoepfner, Kerstin; Klingebiel, Dennis; Knutzen, Simon; Kreuzer, Peter; Merschmeyer, Markus; Meyer, Arnd; Millet, Philipp; Olschewski, Mark; Padeken, Klaas; Papacz, Paul; Pook, Tobias; Radziej, Markus; Reithler, Hans; Rieger, Marcel; Scheuch, Florian; Sonnenschein, Lars; Teyssier, Daniel; Thüer, Sebastian; Cherepanov, Vladimir; Erdogan, Yusuf; Flügge, Günter; Geenen, Heiko; Geisler, Matthias; Hoehle, Felix; Kargoll, Bastian; Kress, Thomas; Kuessel, Yvonne; Künsken, Andreas; Lingemann, Joschka; Nehrkorn, Alexander; Nowack, Andreas; Nugent, Ian Michael; Pistone, Claudia; Pooth, Oliver; Stahl, Achim; Aldaya Martin, Maria; Asin, Ivan; Bartosik, Nazar; Behnke, Olaf; Behrens, Ulf; Bell, Alan James; Borras, Kerstin; Burgmeier, Armin; Campbell, Alan; Choudhury, Somnath; Costanza, Francesco; Diez Pardos, Carmen; Dolinska, Ganna; Dooling, Samantha; Dorland, Tyler; Eckerlin, Guenter; Eckstein, Doris; Eichhorn, Thomas; Flucke, Gero; Gallo, Elisabetta; Garay Garcia, Jasone; Geiser, Achim; Gizhko, Andrii; Gunnellini, Paolo; Hauk, Johannes; Hempel, Maria; Jung, Hannes; Kalogeropoulos, Alexis; Karacheban, Olena; Kasemann, Matthias; Katsas, Panagiotis; Kieseler, Jan; Kleinwort, Claus; Korol, Ievgen; Lange, Wolfgang; Leonard, Jessica; Lipka, Katerina; Lobanov, Artur; Lohmann, Wolfgang; Mankel, Rainer; Marfin, Ihar; Melzer-Pellmann, Isabell-Alissandra; Meyer, Andreas Bernhard; Mittag, Gregor; Mnich, Joachim; Mussgiller, Andreas; Naumann-Emme, Sebastian; Nayak, Aruna; Ntomari, Eleni; Perrey, Hanno; Pitzl, Daniel; Placakyte, Ringaile; Raspereza, Alexei; Roland, Benoit; Sahin, Mehmet Özgür; Saxena, Pooja; Schoerner-Sadenius, Thomas; Schröder, Matthias; Seitz, Claudia; Spannagel, Simon; Trippkewitz, Karim Damun; Walsh, Roberval; Wissing, Christoph; Blobel, Volker; Centis Vignali, Matteo; Draeger, Arne-Rasmus; Erfle, Joachim; Garutti, Erika; Goebel, Kristin; Gonzalez, Daniel; Görner, Martin; Haller, Johannes; Hoffmann, Malte; Höing, Rebekka Sophie; Junkes, Alexandra; Klanner, Robert; Kogler, Roman; Kovalchuk, Nataliia; Lapsien, Tobias; Lenz, Teresa; Marchesini, Ivan; Marconi, Daniele; Meyer, Mareike; Nowatschin, Dominik; Ott, Jochen; Pantaleo, Felice; Peiffer, Thomas; Perieanu, Adrian; Pietsch, Niklas; Poehlsen, Jennifer; Rathjens, Denis; Sander, Christian; Scharf, Christian; Schettler, Hannes; Schleper, Peter; Schlieckau, Eike; Schmidt, Alexander; Schwandt, Joern; Sola, Valentina; Stadie, Hartmut; Steinbrück, Georg; Tholen, Heiner; Troendle, Daniel; Usai, Emanuele; Vanelderen, Lukas; Vanhoefer, Annika; Vormwald, Benedikt; Akbiyik, Melike; Barth, Christian; Baus, Colin; Berger, Joram; Böser, Christian; Butz, Erik; Chwalek, Thorsten; Colombo, Fabio; De Boer, Wim; Descroix, Alexis; Dierlamm, Alexander; Fink, Simon; Frensch, Felix; Friese, Raphael; Giffels, Manuel; Gilbert, Andrew; Haitz, Dominik; Hartmann, Frank; Heindl, Stefan Michael; Husemann, Ulrich; Katkov, Igor; Kornmayer, Andreas; Lobelle Pardo, Patricia; Maier, Benedikt; Mildner, Hannes; Mozer, Matthias Ulrich; Müller, Thomas; Müller, Thomas; Plagge, Michael; Quast, Gunter; Rabbertz, Klaus; Röcker, Steffen; Roscher, Frank; Sieber, Georg; Simonis, Hans-Jürgen; Stober, Fred-Markus Helmut; Ulrich, Ralf; Wagner-Kuhr, Jeannine; Wayand, Stefan; Weber, Marc; Weiler, Thomas; Wöhrmann, Clemens; Wolf, Roger; Anagnostou, Georgios; Daskalakis, Georgios; Geralis, Theodoros; Giakoumopoulou, Viktoria Athina; Kyriakis, Aristotelis; Loukas, Demetrios; Psallidas, Andreas; Topsis-Giotis, Iasonas; Agapitos, Antonis; Kesisoglou, Stilianos; Panagiotou, Apostolos; Saoulidou, Niki; Tziaferi, Eirini; Evangelou, Ioannis; Flouris, Giannis; Foudas, Costas; Kokkas, Panagiotis; Loukas, Nikitas; Manthos, Nikolaos; Papadopoulos, Ioannis; Paradas, Evangelos; Strologas, John; Bencze, Gyorgy; Hajdu, Csaba; Hazi, Andras; Hidas, Pàl; Horvath, Dezso; Sikler, Ferenc; Veszpremi, Viktor; Vesztergombi, Gyorgy; Zsigmond, Anna Julia; Beni, Noemi; Czellar, Sandor; Karancsi, János; Molnar, Jozsef; Szillasi, Zoltan; Bartók, Márton; Makovec, Alajos; Raics, Peter; Trocsanyi, Zoltan Laszlo; Ujvari, Balazs; Mal, Prolay; Mandal, Koushik; Sahoo, Deepak Kumar; Sahoo, Niladribihari; Swain, Sanjay Kumar; Bansal, Sunil; Beri, Suman Bala; Bhatnagar, Vipin; Chawla, Ridhi; Gupta, Ruchi; Bhawandeep, Bhawandeep; Kalsi, Amandeep Kaur; Kaur, Anterpreet; Kaur, Manjit; Kumar, Ramandeep; Mehta, Ankita; Mittal, Monika; Singh, Jasbir; Walia, Genius; Kumar, Ashok; Bhardwaj, Ashutosh; Choudhary, Brajesh C; Garg, Rocky Bala; Kumar, Ajay; Malhotra, Shivali; Naimuddin, Md; Nishu, Nishu; Ranjan, Kirti; Sharma, Ramkrishna; Sharma, Varun; Bhattacharya, Satyaki; Chatterjee, Kalyanmoy; Dey, Sourav; Dutta, Suchandra; Jain, Sandhya; Majumdar, Nayana; Modak, Atanu; Mondal, Kuntal; Mukherjee, Swagata; Mukhopadhyay, Supratik; Roy, Ashim; Roy, Debarati; Roy Chowdhury, Suvankar; Sarkar, Subir; Sharan, Manoj; Abdulsalam, Abdulla; Chudasama, Ruchi; Dutta, Dipanwita; Jha, Vishwajeet; Kumar, Vineet; Mohanty, Ajit Kumar; Pant, Lalit Mohan; Shukla, Prashant; Topkar, Anita; Aziz, Tariq; Banerjee, Sudeshna; Bhowmik, Sandeep; Chatterjee, Rajdeep Mohan; Dewanjee, Ram Krishna; Dugad, Shashikant; Ganguly, Sanmay; Ghosh, Saranya; Guchait, Monoranjan; Gurtu, Atul; Kole, Gouranga; Kumar, Sanjeev; Mahakud, Bibhuprasad; Maity, Manas; Majumder, Gobinda; Mazumdar, Kajari; Mitra, Soureek; Mohanty, Gagan Bihari; Parida, Bibhuti; Sarkar, Tanmay; Sur, Nairit; Sutar, Bajrang; Wickramage, Nadeesha; Chauhan, Shubhanshu; Dube, Sourabh; Kothekar, Kunal; Sharma, Seema; Bakhshiansohi, Hamed; Behnamian, Hadi; Etesami, Seyed Mohsen; Fahim, Ali; Goldouzian, Reza; Khakzad, Mohsen; Mohammadi Najafabadi, Mojtaba; Naseri, Mohsen; Paktinat Mehdiabadi, Saeid; Rezaei Hosseinabadi, Ferdos; Safarzadeh, Batool; Zeinali, Maryam; Felcini, Marta; Grunewald, Martin; Abbrescia, Marcello; Calabria, Cesare; Caputo, Claudio; Colaleo, Anna; Creanza, Donato; Cristella, Leonardo; De Filippis, Nicola; De Palma, Mauro; Fiore, Luigi; Iaselli, Giuseppe; Maggi, Giorgio; Maggi, Marcello; Miniello, Giorgia; My, Salvatore; Nuzzo, Salvatore; Pompili, Alexis; Pugliese, Gabriella; Radogna, Raffaella; Ranieri, Antonio; Selvaggi, Giovanna; Silvestris, Lucia; Venditti, Rosamaria; Verwilligen, Piet; Abbiendi, Giovanni; Battilana, Carlo; Benvenuti, Alberto; Bonacorsi, Daniele; Braibant-Giacomelli, Sylvie; Brigliadori, Luca; Campanini, Renato; Capiluppi, Paolo; Castro, Andrea; Cavallo, Francesca Romana; Chhibra, Simranjit Singh; Codispoti, Giuseppe; Cuffiani, Marco; Dallavalle, Gaetano-Marco; Fabbri, Fabrizio; Fanfani, Alessandra; Fasanella, Daniele; Giacomelli, Paolo; Grandi, Claudio; Guiducci, Luigi; Marcellini, Stefano; Masetti, Gianni; Montanari, Alessandro; Navarria, Francesco; Perrotta, Andrea; Rossi, Antonio; Rovelli, Tiziano; Siroli, Gian Piero; Tosi, Nicolò; Travaglini, Riccardo; Cappello, Gigi; Chiorboli, Massimiliano; Costa, Salvatore; Di Mattia, Alessandro; Giordano, Ferdinando; Potenza, Renato; Tricomi, Alessia; Tuve, Cristina; Barbagli, Giuseppe; Ciulli, Vitaliano; Civinini, Carlo; D'Alessandro, Raffaello; Focardi, Ettore; Gonzi, Sandro; Gori, Valentina; Lenzi, Piergiulio; Meschini, Marco; Paoletti, Simone; Sguazzoni, Giacomo; Tropiano, Antonio; Viliani, Lorenzo; Benussi, Luigi; Bianco, Stefano; Fabbri, Franco; Piccolo, Davide; Primavera, Federica; Calvelli, Valerio; Ferro, Fabrizio; Lo Vetere, Maurizio; Monge, Maria Roberta; Robutti, Enrico; Tosi, Silvano; Brianza, Luca; Dinardo, Mauro Emanuele; Fiorendi, Sara; Gennai, Simone; Gerosa, Raffaele; Ghezzi, Alessio; Govoni, Pietro; Malvezzi, Sandra; Manzoni, Riccardo Andrea; Marzocchi, Badder; Menasce, Dario; Moroni, Luigi; Paganoni, Marco; Pedrini, Daniele; Ragazzi, Stefano; Redaelli, Nicola; Tabarelli de Fatis, Tommaso; Buontempo, Salvatore; Cavallo, Nicola; Di Guida, Salvatore; Esposito, Marco; Fabozzi, Francesco; Iorio, Alberto Orso Maria; Lanza, Giuseppe; Lista, Luca; Meola, Sabino; Merola, Mario; Paolucci, Pierluigi; Sciacca, Crisostomo; Thyssen, Filip; Bacchetta, Nicola; Bellato, Marco; Benato, Lisa; Bisello, Dario; Boletti, Alessio; Carlin, Roberto; Checchia, Paolo; Dall'Osso, Martino; Dosselli, Umberto; Gasparini, Fabrizio; Gasparini, Ugo; Gozzelino, Andrea; Lacaprara, Stefano; Margoni, Martino; Meneguzzo, Anna Teresa; Montecassiano, Fabio; Passaseo, Marina; Pazzini, Jacopo; Pegoraro, Matteo; Pozzobon, Nicola; Simonetto, Franco; Torassa, Ezio; Tosi, Mia; Vanini, Sara; Ventura, Sandro; Zanetti, Marco; Zotto, Pierluigi; Zucchetta, Alberto; Zumerle, Gianni; Braghieri, Alessandro; Magnani, Alice; Montagna, Paolo; Ratti, Sergio P; Re, Valerio; Riccardi, Cristina; Salvini, Paola; Vai, Ilaria; Vitulo, Paolo; Alunni Solestizi, Luisa; Biasini, Maurizio; Bilei, Gian Mario; Ciangottini, Diego; Fanò, Livio; Lariccia, Paolo; Mantovani, Giancarlo; Menichelli, Mauro; Saha, Anirban; Santocchia, Attilio; Androsov, Konstantin; Azzurri, Paolo; Bagliesi, Giuseppe; Bernardini, Jacopo; Boccali, Tommaso; Castaldi, Rino; Ciocci, Maria Agnese; Dell'Orso, Roberto; Donato, Silvio; Fedi, Giacomo; Foà, Lorenzo; Giassi, Alessandro; Grippo, Maria Teresa; Ligabue, Franco; Lomtadze, Teimuraz; Martini, Luca; Messineo, Alberto; Palla, Fabrizio; Rizzi, Andrea; Savoy-Navarro, Aurore; Serban, Alin Titus; Spagnolo, Paolo; Tenchini, Roberto; Tonelli, Guido; Venturi, Andrea; Verdini, Piero Giorgio; Barone, Luciano; Cavallari, Francesca; D'imperio, Giulia; Del Re, Daniele; Diemoz, Marcella; Gelli, Simone; Jorda, Clara; Longo, Egidio; Margaroli, Fabrizio; Meridiani, Paolo; Organtini, Giovanni; Paramatti, Riccardo; Preiato, Federico; Rahatlou, Shahram; Rovelli, Chiara; Santanastasio, Francesco; Traczyk, Piotr; Amapane, Nicola; Arcidiacono, Roberta; Argiro, Stefano; Arneodo, Michele; Bellan, Riccardo; Biino, Cristina; Cartiglia, Nicolo; Costa, Marco; Covarelli, Roberto; Degano, Alessandro; Demaria, Natale; Finco, Linda; Kiani, Bilal; Mariotti, Chiara; Maselli, Silvia; Migliore, Ernesto; Monaco, Vincenzo; Monteil, Ennio; Obertino, Maria Margherita; Pacher, Luca; Pastrone, Nadia; Pelliccioni, Mario; Pinna Angioni, Gian Luca; Ravera, Fabio; Romero, Alessandra; Ruspa, Marta; Sacchi, Roberto; Solano, Ada; Staiano, Amedeo; Tamponi, Umberto; Belforte, Stefano; Candelise, Vieri; Casarsa, Massimo; Cossutti, Fabio; Della Ricca, Giuseppe; Gobbo, Benigno; La Licata, Chiara; Marone, Matteo; Schizzi, Andrea; Zanetti, Anna; Kropivnitskaya, Anna; Nam, Soon-Kwon; Kim, Dong Hee; Kim, Gui Nyun; Kim, Min Suk; Kong, Dae Jung; Lee, Sangeun; Oh, Young Do; Sakharov, Alexandre; Son, Dong-Chul; Brochero Cifuentes, Javier Andres; Kim, Hyunsoo; Kim, Tae Jeong; Song, Sanghyeon; Choi, Suyong; Go, Yeonju; Gyun, Dooyeon; Hong, Byung-Sik; Jo, Mihee; Kim, Hyunchul; Kim, Yongsun; Lee, Byounghoon; Lee, Kisoo; Lee, Kyong Sei; Lee, Songkyo; Park, Sung Keun; Roh, Youn; Yoo, Hwi Dong; Choi, Minkyoo; Kim, Hyunyong; Kim, Ji Hyun; Lee, Jason Sang Hun; Park, Inkyu; Ryu, Geonmo; Ryu, Min Sang; Choi, Young-Il; Goh, Junghwan; Kim, Donghyun; Kwon, Eunhyang; Lee, Jongseok; Yu, Intae; Dudenas, Vytautas; Juodagalvis, Andrius; Vaitkus, Juozas; Ahmed, Ijaz; Ibrahim, Zainol Abidin; Komaragiri, Jyothsna Rani; Md Ali, Mohd Adli Bin; Mohamad Idris, Faridah; Wan Abdullah, Wan Ahmad Tajuddin; Yusli, Mohd Nizam; Casimiro Linares, Edgar; Castilla-Valdez, Heriberto; De La Cruz-Burelo, Eduard; Heredia-De La Cruz, Ivan; Hernandez-Almada, Alberto; Lopez-Fernandez, Ricardo; Sánchez Hernández, Alberto; Carrillo Moreno, Salvador; Vazquez Valencia, Fabiola; Pedraza, Isabel; Salazar Ibarguen, Humberto Antonio; Morelos Pineda, Antonio; Krofcheck, David; Butler, Philip H; Ahmad, Ashfaq; Ahmad, Muhammad; Hassan, Qamar; Hoorani, Hafeez R; Khan, Wajid Ali; Khurshid, Taimoor; Shoaib, Muhammad; Bialkowska, Helena; Bluj, Michal; Boimska, Bożena; Frueboes, Tomasz; Górski, Maciej; Kazana, Malgorzata; Nawrocki, Krzysztof; Romanowska-Rybinska, Katarzyna; Szleper, Michal; Zalewski, Piotr; Brona, Grzegorz; Bunkowski, Karol; Byszuk, Adrian; Doroba, Krzysztof; Kalinowski, Artur; Konecki, Marcin; Krolikowski, Jan; Misiura, Maciej; Olszewski, Michal; Pozniak, Krzysztof; Walczak, Marek; Bargassa, Pedrame; Beirão Da Cruz E Silva, Cristóvão; Di Francesco, Agostino; Faccioli, Pietro; Ferreira Parracho, Pedro Guilherme; Gallinaro, Michele; Leonardo, Nuno; Lloret Iglesias, Lara; Nguyen, Federico; Rodrigues Antunes, Joao; Seixas, Joao; Toldaiev, Oleksii; Vadruccio, Daniele; Varela, Joao; Vischia, Pietro; Afanasiev, Serguei; Bunin, Pavel; Gavrilenko, Mikhail; Golutvin, Igor; Gorbunov, Ilya; Kamenev, Alexey; Karjavin, Vladimir; Konoplyanikov, Viktor; Lanev, Alexander; Malakhov, Alexander; Matveev, Viktor; Moisenz, Petr; Palichik, Vladimir; Perelygin, Victor; Shmatov, Sergey; Shulha, Siarhei; Skatchkov, Nikolai; Smirnov, Vitaly; Zarubin, Anatoli; Golovtsov, Victor; Ivanov, Yury; Kim, Victor; Kuznetsova, Ekaterina; Levchenko, Petr; Murzin, Victor; Oreshkin, Vadim; Smirnov, Igor; Sulimov, Valentin; Uvarov, Lev; Vavilov, Sergey; Vorobyev, Alexey; Andreev, Yuri; Dermenev, Alexander; Gninenko, Sergei; Golubev, Nikolai; Karneyeu, Anton; Kirsanov, Mikhail; Krasnikov, Nikolai; Pashenkov, Anatoli; Tlisov, Danila; Toropin, Alexander; Epshteyn, Vladimir; Gavrilov, Vladimir; Lychkovskaya, Natalia; Popov, Vladimir; Pozdnyakov, Ivan; Safronov, Grigory; Spiridonov, Alexander; Vlasov, Evgueni; Zhokin, Alexander; Bylinkin, Alexander; Andreev, Vladimir; Azarkin, Maksim; Dremin, Igor; Kirakosyan, Martin; Leonidov, Andrey; Mesyats, Gennady; Rusakov, Sergey V; Baskakov, Alexey; Belyaev, Andrey; Boos, Edouard; Dubinin, Mikhail; Dudko, Lev; Ershov, Alexander; Gribushin, Andrey; Kaminskiy, Alexandre; Klyukhin, Vyacheslav; Kodolova, Olga; Lokhtin, Igor; Miagkov, Igor; Obraztsov, Stepan; Petrushanko, Sergey; Savrin, Viktor; Azhgirey, Igor; Bayshev, Igor; Bitioukov, Sergei; Kachanov, Vassili; Kalinin, Alexey; Konstantinov, Dmitri; Krychkine, Victor; Petrov, Vladimir; Ryutin, Roman; Sobol, Andrei; Tourtchanovitch, Leonid; Troshin, Sergey; Tyurin, Nikolay; Uzunian, Andrey; Volkov, Alexey; Adzic, Petar; Milosevic, Jovan; Rekovic, Vladimir; Alcaraz Maestre, Juan; Calvo, Enrique; Cerrada, Marcos; Chamizo Llatas, Maria; Colino, Nicanor; De La Cruz, Begona; Delgado Peris, Antonio; Domínguez Vázquez, Daniel; Escalante Del Valle, Alberto; Fernandez Bedoya, Cristina; Fernández Ramos, Juan Pablo; Flix, Jose; Fouz, Maria Cruz; Garcia-Abia, Pablo; Gonzalez Lopez, Oscar; Goy Lopez, Silvia; Hernandez, Jose M; Josa, Maria Isabel; Navarro De Martino, Eduardo; Pérez-Calero Yzquierdo, Antonio María; Puerta Pelayo, Jesus; Quintario Olmeda, Adrián; Redondo, Ignacio; Romero, Luciano; Santaolalla, Javier; Senghi Soares, Mara; Albajar, Carmen; de Trocóniz, Jorge F; Missiroli, Marino; Moran, Dermot; Cuevas, Javier; Fernandez Menendez, Javier; Folgueras, Santiago; Gonzalez Caballero, Isidro; Palencia Cortezon, Enrique; Vizan Garcia, Jesus Manuel; Cabrillo, Iban Jose; Calderon, Alicia; Castiñeiras De Saa, Juan Ramon; De Castro Manzano, Pablo; Duarte Campderros, Jordi; Fernandez, Marcos; Garcia-Ferrero, Juan; Gomez, Gervasio; Lopez Virto, Amparo; Marco, Jesus; Marco, Rafael; Martinez Rivero, Celso; Matorras, Francisco; Munoz Sanchez, Francisca Javiela; Piedra Gomez, Jonatan; Rodrigo, Teresa; Rodríguez-Marrero, Ana Yaiza; Ruiz-Jimeno, Alberto; Scodellaro, Luca; Trevisani, Nicolò; Vila, Ivan; Vilar Cortabitarte, Rocio; Abbaneo, Duccio; Auffray, Etiennette; Auzinger, Georg; Bachtis, Michail; Baillon, Paul; Ball, Austin; Barney, David; Benaglia, Andrea; Bendavid, Joshua; Benhabib, Lamia; Benitez, Jose F; Berruti, Gaia Maria; Bloch, Philippe; Bocci, Andrea; Bonato, Alessio; Botta, Cristina; Breuker, Horst; Camporesi, Tiziano; Castello, Roberto; Cerminara, Gianluca; D'Alfonso, Mariarosaria; D'Enterria, David; Dabrowski, Anne; Daponte, Vincenzo; David Tinoco Mendes, Andre; De Gruttola, Michele; De Guio, Federico; De Roeck, Albert; De Visscher, Simon; Di Marco, Emanuele; Dobson, Marc; Dordevic, Milos; Dorney, Brian; Du Pree, Tristan; Dünser, Marc; Dupont, Niels; Elliott-Peisert, Anna; Franzoni, Giovanni; Funk, Wolfgang; Gigi, Dominique; Gill, Karl; Giordano, Domenico; Girone, Maria; Glege, Frank; Guida, Roberto; Gundacker, Stefan; Guthoff, Moritz; Hammer, Josef; Harris, Philip; Hegeman, Jeroen; Innocente, Vincenzo; Janot, Patrick; Kirschenmann, Henning; Kortelainen, Matti J; Kousouris, Konstantinos; Krajczar, Krisztian; Lecoq, Paul; Lourenco, Carlos; Lucchini, Marco Toliman; Magini, Nicolo; Malgeri, Luca; Mannelli, Marcello; Martelli, Arabella; Masetti, Lorenzo; Meijers, Frans; Mersi, Stefano; Meschi, Emilio; Moortgat, Filip; Morovic, Srecko; Mulders, Martijn; Nemallapudi, Mythra Varun; Neugebauer, Hannes; Orfanelli, Styliani; Orsini, Luciano; Pape, Luc; Perez, Emmanuelle; Peruzzi, Marco; Petrilli, Achille; Petrucciani, Giovanni; Pfeiffer, Andreas; Piparo, Danilo; Racz, Attila; Rolandi, Gigi; Rovere, Marco; Ruan, Manqi; Sakulin, Hannes; Schäfer, Christoph; Schwick, Christoph; Seidel, Markus; Sharma, Archana; Silva, Pedro; Simon, Michal; Sphicas, Paraskevas; Steggemann, Jan; Stieger, Benjamin; Stoye, Markus; Takahashi, Yuta; Treille, Daniel; Triossi, Andrea; Tsirou, Andromachi; Veres, Gabor Istvan; Wardle, Nicholas; Wöhri, Hermine Katharina; Zagoździńska, Agnieszka; Zeuner, Wolfram Dietrich; Bertl, Willi; Deiters, Konrad; Erdmann, Wolfram; Horisberger, Roland; Ingram, Quentin; Kaestli, Hans-Christian; Kotlinski, Danek; Langenegger, Urs; Renker, Dieter; Rohe, Tilman; Bachmair, Felix; Bäni, Lukas; Bianchini, Lorenzo; Casal, Bruno; Dissertori, Günther; Dittmar, Michael; Donegà, Mauro; Eller, Philipp; Grab, Christoph; Heidegger, Constantin; Hits, Dmitry; Hoss, Jan; Kasieczka, Gregor; Lustermann, Werner; Mangano, Boris; Marionneau, Matthieu; Martinez Ruiz del Arbol, Pablo; Masciovecchio, Mario; Meister, Daniel; Micheli, Francesco; Musella, Pasquale; Nessi-Tedaldi, Francesca; Pandolfi, Francesco; Pata, Joosep; Pauss, Felicitas; Perrozzi, Luca; Quittnat, Milena; Rossini, Marco; Starodumov, Andrei; Takahashi, Maiko; Tavolaro, Vittorio Raoul; Theofilatos, Konstantinos; Wallny, Rainer; Aarrestad, Thea Klaeboe; Amsler, Claude; Caminada, Lea; Canelli, Maria Florencia; Chiochia, Vincenzo; De Cosa, Annapaola; Galloni, Camilla; Hinzmann, Andreas; Hreus, Tomas; Kilminster, Benjamin; Lange, Clemens; Ngadiuba, Jennifer; Pinna, Deborah; Robmann, Peter; Ronga, Frederic Jean; Salerno, Daniel; Yang, Yong; Cardaci, Marco; Chen, Kuan-Hsin; Doan, Thi Hien; Jain, Shilpi; Khurana, Raman; Konyushikhin, Maxim; Kuo, Chia-Ming; Lin, Willis; Lu, Yun-Ju; Yu, Shin-Shan; Kumar, Arun; Bartek, Rachel; Chang, Paoti; Chang, You-Hao; Chang, Yu-Wei; Chao, Yuan; Chen, Kai-Feng; Chen, Po-Hsun; Dietz, Charles; Fiori, Francesco; Grundler, Ulysses; Hou, George Wei-Shu; Hsiung, Yee; Liu, Yueh-Feng; Lu, Rong-Shyang; Miñano Moya, Mercedes; Petrakou, Eleni; Tsai, Jui-fa; Tzeng, Yeng-Ming; Asavapibhop, Burin; Kovitanggoon, Kittikul; Singh, Gurpreet; Srimanobhas, Norraphat; Suwonjandee, Narumon; Adiguzel, Aytul; Bakirci, Mustafa Numan; Demiroglu, Zuhal Seyma; Dozen, Candan; Eskut, Eda; Girgis, Semiray; Gokbulut, Gul; Guler, Yalcin; Gurpinar, Emine; Hos, Ilknur; Kangal, Evrim Ersin; Onengut, Gulsen; Ozdemir, Kadri; Polatoz, Ayse; Sunar Cerci, Deniz; Tali, Bayram; Topakli, Huseyin; Vergili, Mehmet; Zorbilmez, Caglar; Akin, Ilina Vasileva; Bilin, Bugra; Bilmis, Selcuk; Isildak, Bora; Karapinar, Guler; Yalvac, Metin; Zeyrek, Mehmet; Gülmez, Erhan; Kaya, Mithat; Kaya, Ozlem; Yetkin, Elif Asli; Yetkin, Taylan; Cakir, Altan; Cankocak, Kerem; Sen, Sercan; Vardarlı, Fuat Ilkehan; Grynyov, Boris; Levchuk, Leonid; Sorokin, Pavel; Aggleton, Robin; Ball, Fionn; Beck, Lana; Brooke, James John; Clement, Emyr; Cussans, David; Flacher, Henning; Goldstein, Joel; Grimes, Mark; Heath, Greg P; Heath, Helen F; Jacob, Jeson; Kreczko, Lukasz; Lucas, Chris; Meng, Zhaoxia; Newbold, Dave M; Paramesvaran, Sudarshan; Poll, Anthony; Sakuma, Tai; Seif El Nasr-storey, Sarah; Senkin, Sergey; Smith, Dominic; Smith, Vincent J; Bell, Ken W; Belyaev, Alexander; Brew, Christopher; Brown, Robert M; Calligaris, Luigi; Cieri, Davide; Cockerill, David JA; Coughlan, John A; Harder, Kristian; Harper, Sam; Olaiya, Emmanuel; Petyt, David; Shepherd-Themistocleous, Claire; Thea, Alessandro; Tomalin, Ian R; Williams, Thomas; Womersley, William John; Worm, Steven; Baber, Mark; Bainbridge, Robert; Buchmuller, Oliver; Bundock, Aaron; Burton, Darren; Casasso, Stefano; Citron, Matthew; Colling, David; Corpe, Louie; Cripps, Nicholas; Dauncey, Paul; Davies, Gavin; De Wit, Adinda; Della Negra, Michel; Dunne, Patrick; Elwood, Adam; Ferguson, William; Fulcher, Jonathan; Futyan, David; Hall, Geoffrey; Iles, Gregory; Kenzie, Matthew; Lane, Rebecca; Lucas, Robyn; Lyons, Louis; Magnan, Anne-Marie; Malik, Sarah; Nash, Jordan; Nikitenko, Alexander; Pela, Joao; Pesaresi, Mark; Petridis, Konstantinos; Raymond, David Mark; Richards, Alexander; Rose, Andrew; Seez, Christopher; Tapper, Alexander; Uchida, Kirika; Vazquez Acosta, Monica; Virdee, Tejinder; Zenz, Seth Conrad; Cole, Joanne; Hobson, Peter R; Khan, Akram; Kyberd, Paul; Leggat, Duncan; Leslie, Dawn; Reid, Ivan; Symonds, Philip; Teodorescu, Liliana; Turner, Mark; Borzou, Ahmad; Call, Kenneth; Dittmann, Jay; Hatakeyama, Kenichi; Liu, Hongxuan; Pastika, Nathaniel; Charaf, Otman; Cooper, Seth; Henderson, Conor; Rumerio, Paolo; Arcaro, Daniel; Avetisyan, Aram; Bose, Tulika; Fantasia, Cory; Gastler, Daniel; Lawson, Philip; Rankin, Dylan; Richardson, Clint; Rohlf, James; St John, Jason; Sulak, Lawrence; Zou, David; Alimena, Juliette; Berry, Edmund; Bhattacharya, Saptaparna; Cutts, David; Dhingra, Nitish; Ferapontov, Alexey; Garabedian, Alex; Hakala, John; Heintz, Ulrich; Laird, Edward; Landsberg, Greg; Mao, Zaixing; Narain, Meenakshi; Piperov, Stefan; Sagir, Sinan; Syarif, Rizki; Breedon, Richard; Breto, Guillermo; Calderon De La Barca Sanchez, Manuel; Chauhan, Sushil; Chertok, Maxwell; Conway, John; Conway, Rylan; Cox, Peter Timothy; Erbacher, Robin; Gardner, Michael; Ko, Winston; Lander, Richard; Mulhearn, Michael; Pellett, Dave; Pilot, Justin; Ricci-Tam, Francesca; Shalhout, Shalhout; Smith, John; Squires, Michael; Stolp, Dustin; Tripathi, Mani; Wilbur, Scott; Yohay, Rachel; Cousins, Robert; Everaerts, Pieter; Farrell, Chris; Hauser, Jay; Ignatenko, Mikhail; Saltzberg, David; Takasugi, Eric; Valuev, Vyacheslav; Weber, Matthias; Burt, Kira; Clare, Robert; Ellison, John Anthony; Gary, J William; Hanson, Gail; Heilman, Jesse; Paneva, Mirena Ivova; Jandir, Pawandeep; Kennedy, Elizabeth; Lacroix, Florent; Long, Owen Rosser; Luthra, Arun; Malberti, Martina; Olmedo Negrete, Manuel; Shrinivas, Amithabh; Wei, Hua; Wimpenny, Stephen; Yates, Brent; Branson, James G; Cerati, Giuseppe Benedetto; Cittolin, Sergio; D'Agnolo, Raffaele Tito; Derdzinski, Mark; Holzner, André; Kelley, Ryan; Klein, Daniel; Letts, James; Macneill, Ian; Olivito, Dominick; Padhi, Sanjay; Pieri, Marco; Sani, Matteo; Sharma, Vivek; Simon, Sean; Tadel, Matevz; Vartak, Adish; Wasserbaech, Steven; Welke, Charles; Würthwein, Frank; Yagil, Avraham; Zevi Della Porta, Giovanni; Bradmiller-Feld, John; Campagnari, Claudio; Dishaw, Adam; Dutta, Valentina; Flowers, Kristen; Franco Sevilla, Manuel; Geffert, Paul; George, Christopher; Golf, Frank; Gouskos, Loukas; Gran, Jason; Incandela, Joe; Mccoll, Nickolas; Mullin, Sam Daniel; Richman, Jeffrey; Stuart, David; Suarez, Indara; West, Christopher; Yoo, Jaehyeok; Anderson, Dustin; Apresyan, Artur; Bornheim, Adolf; Bunn, Julian; Chen, Yi; Duarte, Javier; Mott, Alexander; Newman, Harvey B; Pena, Cristian; Pierini, Maurizio; Spiropulu, Maria; Vlimant, Jean-Roch; Xie, Si; Zhu, Ren-Yuan; Andrews, Michael Benjamin; Azzolini, Virginia; Calamba, Aristotle; Carlson, Benjamin; Ferguson, Thomas; Paulini, Manfred; Russ, James; Sun, Menglei; Vogel, Helmut; Vorobiev, Igor; Cumalat, John Perry; Ford, William T; Gaz, Alessandro; Jensen, Frank; Johnson, Andrew; Krohn, Michael; Mulholland, Troy; Nauenberg, Uriel; Stenson, Kevin; Wagner, Stephen Robert; Alexander, James; Chatterjee, Avishek; Chaves, Jorge; Chu, Jennifer; Dittmer, Susan; Eggert, Nicholas; Mirman, Nathan; Nicolas Kaufman, Gala; Patterson, Juliet Ritchie; Rinkevicius, Aurelijus; Ryd, Anders; Skinnari, Louise; Soffi, Livia; Sun, Werner; Tan, Shao Min; Teo, Wee Don; Thom, Julia; Thompson, Joshua; Tucker, Jordan; Weng, Yao; Wittich, Peter; Abdullin, Salavat; Albrow, Michael; Anderson, Jacob; Apollinari, Giorgio; Banerjee, Sunanda; Bauerdick, Lothar AT; Beretvas, Andrew; Berryhill, Jeffrey; Bhat, Pushpalatha C; Bolla, Gino; Burkett, Kevin; Butler, Joel Nathan; Cheung, Harry; Chlebana, Frank; Cihangir, Selcuk; Elvira, Victor Daniel; Fisk, Ian; Freeman, Jim; Gottschalk, Erik; Gray, Lindsey; Green, Dan; Grünendahl, Stefan; Gutsche, Oliver; Hanlon, Jim; Hare, Daryl; Harris, Robert M; Hasegawa, Satoshi; Hirschauer, James; Hu, Zhen; Jayatilaka, Bodhitha; Jindariani, Sergo; Johnson, Marvin; Joshi, Umesh; Jung, Andreas Werner; Klima, Boaz; Kreis, Benjamin; Kwan, Simon; Lammel, Stephan; Linacre, Jacob; Lincoln, Don; Lipton, Ron; Liu, Tiehui; Lopes De Sá, Rafael; Lykken, Joseph; Maeshima, Kaori; Marraffino, John Michael; Martinez Outschoorn, Verena Ingrid; Maruyama, Sho; Mason, David; McBride, Patricia; Merkel, Petra; Mishra, Kalanand; Mrenna, Stephen; Nahn, Steve; Newman-Holmes, Catherine; O'Dell, Vivian; Pedro, Kevin; Prokofyev, Oleg; Rakness, Gregory; Sexton-Kennedy, Elizabeth; Soha, Aron; Spalding, William J; Spiegel, Leonard; Taylor, Lucas; Tkaczyk, Slawek; Tran, Nhan Viet; Uplegger, Lorenzo; Vaandering, Eric Wayne; Vernieri, Caterina; Verzocchi, Marco; Vidal, Richard; Weber, Hannsjoerg Artur; Whitbeck, Andrew; Yang, Fan; Acosta, Darin; Avery, Paul; Bortignon, Pierluigi; Bourilkov, Dimitri; Carnes, Andrew; Carver, Matthew; Curry, David; Das, Souvik; Di Giovanni, Gian Piero; Field, Richard D; Furic, Ivan-Kresimir; Gleyzer, Sergei V; Hugon, Justin; Konigsberg, Jacobo; Korytov, Andrey; Low, Jia Fu; Ma, Peisen; Matchev, Konstantin; Mei, Hualin; Milenovic, Predrag; Mitselmakher, Guenakh; Rank, Douglas; Rossin, Roberto; Shchutska, Lesya; Snowball, Matthew; Sperka, David; Terentyev, Nikolay; Thomas, Laurent; Wang, Jian; Wang, Sean-Jiun; Yelton, John; Hewamanage, Samantha; Linn, Stephan; Markowitz, Pete; Martinez, German; Rodriguez, Jorge Luis; Ackert, Andrew; Adams, Jordon Rowe; Adams, Todd; Askew, Andrew; Bochenek, Joseph; Diamond, Brendan; Haas, Jeff; Hagopian, Sharon; Hagopian, Vasken; Johnson, Kurtis F; Khatiwada, Ajeeta; Prosper, Harrison; Weinberg, Marc; Baarmand, Marc M; Bhopatkar, Vallary; Colafranceschi, Stefano; Hohlmann, Marcus; Kalakhety, Himali; Noonan, Daniel; Roy, Titas; Yumiceva, Francisco; Adams, Mark Raymond; Apanasevich, Leonard; Berry, Douglas; Betts, Russell Richard; Bucinskaite, Inga; Cavanaugh, Richard; Evdokimov, Olga; Gauthier, Lucie; Gerber, Cecilia Elena; Hofman, David Jonathan; Kurt, Pelin; O'Brien, Christine; Sandoval Gonzalez, Irving Daniel; Silkworth, Christopher; Turner, Paul; Varelas, Nikos; Wu, Zhenbin; Zakaria, Mohammed; Bilki, Burak; Clarida, Warren; Dilsiz, Kamuran; Durgut, Süleyman; Gandrajula, Reddy Pratap; Haytmyradov, Maksat; Khristenko, Viktor; Merlo, Jean-Pierre; Mermerkaya, Hamit; Mestvirishvili, Alexi; Moeller, Anthony; Nachtman, Jane; Ogul, Hasan; Onel, Yasar; Ozok, Ferhat; Penzo, Aldo; Snyder, Christina; Tiras, Emrah; Wetzel, James; Yi, Kai; Anderson, Ian; Barnett, Bruce Arnold; Blumenfeld, Barry; Eminizer, Nicholas; Fehling, David; Feng, Lei; Gritsan, Andrei; Maksimovic, Petar; Martin, Christopher; Osherson, Marc; Roskes, Jeffrey; Cocoros, Alice; Sarica, Ulascan; Swartz, Morris; Xiao, Meng; Xin, Yongjie; You, Can; Baringer, Philip; Bean, Alice; Benelli, Gabriele; Bruner, Christopher; Kenny III, Raymond Patrick; Majumder, Devdatta; Malek, Magdalena; Murray, Michael; Sanders, Stephen; Stringer, Robert; Wang, Quan; Ivanov, Andrew; Kaadze, Ketino; Khalil, Sadia; Makouski, Mikhail; Maravin, Yurii; Mohammadi, Abdollah; Saini, Lovedeep Kaur; Skhirtladze, Nikoloz; Toda, Sachiko; Lange, David; Rebassoo, Finn; Wright, Douglas; Anelli, Christopher; Baden, Drew; Baron, Owen; Belloni, Alberto; Calvert, Brian; Eno, Sarah Catherine; Ferraioli, Charles; Gomez, Jaime; Hadley, Nicholas John; Jabeen, Shabnam; Kellogg, Richard G; Kolberg, Ted; Kunkle, Joshua; Lu, Ying; Mignerey, Alice; Shin, Young Ho; Skuja, Andris; Tonjes, Marguerite; Tonwar, Suresh C; Apyan, Aram; Barbieri, Richard; Baty, Austin; Bierwagen, Katharina; Brandt, Stephanie; Busza, Wit; Cali, Ivan Amos; Demiragli, Zeynep; Di Matteo, Leonardo; Gomez Ceballos, Guillelmo; Goncharov, Maxim; Gulhan, Doga; Iiyama, Yutaro; Innocenti, Gian Michele; Klute, Markus; Kovalskyi, Dmytro; Lai, Yue Shi; Lee, Yen-Jie; Levin, Andrew; Luckey, Paul David; Marini, Andrea Carlo; Mcginn, Christopher; Mironov, Camelia; Narayanan, Siddharth; Niu, Xinmei; Paus, Christoph; Ralph, Duncan; Roland, Christof; Roland, Gunther; Salfeld-Nebgen, Jakob; Stephans, George; Sumorok, Konstanty; Varma, Mukund; Velicanu, Dragos; Veverka, Jan; Wang, Jing; Wang, Ta-Wei; Wyslouch, Bolek; Yang, Mingming; Zhukova, Victoria; Dahmes, Bryan; Evans, Andrew; Finkel, Alexey; Gude, Alexander; Hansen, Peter; Kalafut, Sean; Kao, Shih-Chuan; Klapoetke, Kevin; Kubota, Yuichi; Lesko, Zachary; Mans, Jeremy; Nourbakhsh, Shervin; Ruckstuhl, Nicole; Rusack, Roger; Tambe, Norbert; Turkewitz, Jared; Acosta, John Gabriel; Oliveros, Sandra; Avdeeva, Ekaterina; Bloom, Kenneth; Bose, Suvadeep; Claes, Daniel R; Dominguez, Aaron; Fangmeier, Caleb; Gonzalez Suarez, Rebeca; Kamalieddin, Rami; Keller, Jason; Knowlton, Dan; Kravchenko, Ilya; Meier, Frank; Monroy, Jose; Ratnikov, Fedor; Siado, Joaquin Emilo; Snow, Gregory R; Alyari, Maral; Dolen, James; George, Jimin; Godshalk, Andrew; Harrington, Charles; Iashvili, Ia; Kaisen, Josh; Kharchilava, Avto; Kumar, Ashish; Rappoccio, Salvatore; Roozbahani, Bahareh; Alverson, George; Barberis, Emanuela; Baumgartel, Darin; Chasco, Matthew; Hortiangtham, Apichart; Massironi, Andrea; Morse, David Michael; Nash, David; Orimoto, Toyoko; Teixeira De Lima, Rafael; Trocino, Daniele; Wang, Ren-Jie; Wood, Darien; Zhang, Jinzhong; Hahn, Kristan Allan; Kubik, Andrew; Mucia, Nicholas; Odell, Nathaniel; Pollack, Brian; Pozdnyakov, Andrey; Schmitt, Michael Henry; Stoynev, Stoyan; Sung, Kevin; Trovato, Marco; Velasco, Mayda; Brinkerhoff, Andrew; Dev, Nabarun; Hildreth, Michael; Jessop, Colin; Karmgard, Daniel John; Kellams, Nathan; Lannon, Kevin; Lynch, Sean; Marinelli, Nancy; Meng, Fanbo; Mueller, Charles; Musienko, Yuri; Pearson, Tessa; Planer, Michael; Reinsvold, Allison; Ruchti, Randy; Smith, Geoffrey; Taroni, Silvia; Valls, Nil; Wayne, Mitchell; Wolf, Matthias; Woodard, Anna; Antonelli, Louis; Brinson, Jessica; Bylsma, Ben; Durkin, Lloyd Stanley; Flowers, Sean; Hart, Andrew; Hill, Christopher; Hughes, Richard; Ji, Weifeng; Kotov, Khristian; Ling, Ta-Yung; Liu, Bingxuan; Luo, Wuming; Puigh, Darren; Rodenburg, Marissa; Winer, Brian L; Wulsin, Howard Wells; Driga, Olga; Elmer, Peter; Hardenbrook, Joshua; Hebda, Philip; Koay, Sue Ann; Lujan, Paul; Marlow, Daniel; Medvedeva, Tatiana; Mooney, Michael; Olsen, James; Palmer, Christopher; Piroué, Pierre; Saka, Halil; Stickland, David; Tully, Christopher; Zuranski, Andrzej; Malik, Sudhir; Barnes, Virgil E; Benedetti, Daniele; Bortoletto, Daniela; Gutay, Laszlo; Jha, Manoj; Jones, Matthew; Jung, Kurt; Miller, David Harry; Neumeister, Norbert; Radburn-Smith, Benjamin Charles; Shi, Xin; Shipsey, Ian; Silvers, David; Sun, Jian; Svyatkovskiy, Alexey; Wang, Fuqiang; Xie, Wei; Xu, Lingshan; Parashar, Neeti; Stupak, John; Adair, Antony; Akgun, Bora; Chen, Zhenyu; Ecklund, Karl Matthew; Geurts, Frank JM; Guilbaud, Maxime; Li, Wei; Michlin, Benjamin; Northup, Michael; Padley, Brian Paul; Redjimi, Radia; Roberts, Jay; Rorie, Jamal; Tu, Zhoudunming; Zabel, James; Betchart, Burton; Bodek, Arie; de Barbaro, Pawel; Demina, Regina; Eshaq, Yossof; Ferbel, Thomas; Galanti, Mario; Garcia-Bellido, Aran; Han, Jiyeon; Harel, Amnon; Hindrichs, Otto; Khukhunaishvili, Aleko; Petrillo, Gianluca; Tan, Ping; Verzetti, Mauro; Arora, Sanjay; Barker, Anthony; Chou, John Paul; Contreras-Campana, Christian; Contreras-Campana, Emmanuel; Duggan, Daniel; Ferencek, Dinko; Gershtein, Yuri; Gray, Richard; Halkiadakis, Eva; Hidas, Dean; Hughes, Elliot; Kaplan, Steven; Kunnawalkam Elayavalli, Raghav; Lath, Amitabh; Nash, Kevin; Panwalkar, Shruti; Park, Michael; Salur, Sevil; Schnetzer, Steve; Sheffield, David; Somalwar, Sunil; Stone, Robert; Thomas, Scott; Thomassen, Peter; Walker, Matthew; Foerster, Mark; Riley, Grant; Rose, Keith; Spanier, Stefan; York, Andrew; Bouhali, Othmane; Castaneda Hernandez, Alfredo; Dalchenko, Mykhailo; De Mattia, Marco; Delgado, Andrea; Dildick, Sven; Eusebi, Ricardo; Gilmore, Jason; Kamon, Teruki; Krutelyov, Vyacheslav; Mueller, Ryan; Osipenkov, Ilya; Pakhotin, Yuriy; Patel, Rishi; Perloff, Alexx; Rose, Anthony; Safonov, Alexei; Tatarinov, Aysen; Ulmer, Keith; Akchurin, Nural; Cowden, Christopher; Damgov, Jordan; Dragoiu, Cosmin; Dudero, Phillip Russell; Faulkner, James; Kunori, Shuichi; Lamichhane, Kamal; Lee, Sung Won; Libeiro, Terence; Undleeb, Sonaina; Volobouev, Igor; Appelt, Eric; Delannoy, Andrés G; Greene, Senta; Gurrola, Alfredo; Janjam, Ravi; Johns, Willard; Maguire, Charles; Mao, Yaxian; Melo, Andrew; Ni, Hong; Sheldon, Paul; Snook, Benjamin; Tuo, Shengquan; Velkovska, Julia; Xu, Qiao; Arenton, Michael Wayne; Cox, Bradley; Francis, Brian; Goodell, Joseph; Hirosky, Robert; Ledovskoy, Alexander; Li, Hengne; Lin, Chuanzhe; Neu, Christopher; Sinthuprasith, Tutanon; Sun, Xin; Wang, Yanchu; Wolfe, Evan; Wood, John; Xia, Fan; Clarke, Christopher; Harr, Robert; Karchin, Paul Edmund; Kottachchi Kankanamge Don, Chamath; Lamichhane, Pramod; Sturdy, Jared; Belknap, Donald; Carlsmith, Duncan; Cepeda, Maria; Dasu, Sridhara; Dodd, Laura; Duric, Senka; Gomber, Bhawna; Grothe, Monika; Hall-Wilton, Richard; Herndon, Matthew; Hervé, Alain; Klabbers, Pamela; Lanaro, Armando; Levine, Aaron; Long, Kenneth; Loveless, Richard; Mohapatra, Ajit; Ojalvo, Isabel; Perry, Thomas; Pierro, Giuseppe Antonio; Polese, Giovanni; Ruggles, Tyler; Sarangi, Tapas; Savin, Alexander; Sharma, Archana; Smith, Nicholas; Smith, Wesley H; Taylor, Devin; Woods, Nathaniel

    2017-01-24

    This paper describes the CMS trigger system and its performance during Run 1 of the LHC. The trigger system consists of two levels designed to select events of potential physics interest from a GHz (MHz) interaction rate of proton-proton (heavy ion) collisions. The first level of the trigger is implemented in hardware, and selects events containing detector signals consistent with an electron, photon, muon, $\\tau$ lepton, jet, or missing transverse energy. A programmable menu of up to 128 object-based algorithms is used to select events for subsequent processing. The trigger thresholds are adjusted to the LHC instantaneous luminosity during data taking in order to restrict the output rate to 100 kHz, the upper limit imposed by the CMS readout electronics. The second level, implemented in software, further refines the purity of the output stream, selecting an average rate of 400 Hz for offline event storage. The objectives, strategy and performance of the trigger system during the LHC Run 1 are described.

  11. Quantitative Hydrocarbon Surface Analysis

    Science.gov (United States)

    Douglas, Vonnie M.

    2000-01-01

    The elimination of ozone depleting substances, such as carbon tetrachloride, has resulted in the use of new analytical techniques for cleanliness verification and contamination sampling. The last remaining application at Rocketdyne which required a replacement technique was the quantitative analysis of hydrocarbons by infrared spectrometry. This application, which previously utilized carbon tetrachloride, was successfully modified using the SOC-400, a compact portable FTIR manufactured by Surface Optics Corporation. This instrument can quantitatively measure and identify hydrocarbons from solvent flush of hardware as well as directly analyze the surface of metallic components without the use of ozone depleting chemicals. Several sampling accessories are utilized to perform analysis for various applications.

  12. Synthesis of nanodispersible 6-aryl-2,4-diamino-1,3,5-triazine and its derivatives

    International Nuclear Information System (INIS)

    Padalkar, Vikas S.; Patil, Vikas S.; Phatangare, Kiran R.; Gupta, Vinod D.; Umape, Prashant G.; Sekar, N.

    2010-01-01

    A series of novel branched derivatives of 6-aryl-2,4-diamino-1,3,5-triazine from corresponding aryl nitriles and dicyanodiamide was synthesized. These compounds show a nanodispersibility and good thermal stability.

  13. The ATLAS Tau Trigger

    CERN Document Server

    Rados, PK; The ATLAS collaboration

    2014-01-01

    Physics processes involving tau leptons play a crucial role in understanding particle physics at the high energy frontier. The ability to efficiently trigger on events containing hadronic tau decays is therefore of particular importance to the ATLAS experiment. During the 2012 run, the Large Hadronic Collder (LHC) reached instantaneous luminosities of nearly $10^{34} cm^{-2}s^{-1}$ with bunch crossings occurring every $50 ns$. This resulted in a huge event rate and a high probability of overlapping interactions per bunch crossing (pile-up). With this in mind it was necessary to design an ATLAS tau trigger system that could reduce the event rate to a manageable level, while efficiently extracting the most interesting physics events in a pile-up robust manner. In this poster the ATLAS tau trigger is described, its performance during 2012 is presented, and the outlook for the LHC Run II is briefly summarized.

  14. Microfabricated triggered vacuum switch

    Science.gov (United States)

    Roesler, Alexander W [Tijeras, NM; Schare, Joshua M [Albuquerque, NM; Bunch, Kyle [Albuquerque, NM

    2010-05-11

    A microfabricated vacuum switch is disclosed which includes a substrate upon which an anode, cathode and trigger electrode are located. A cover is sealed over the substrate under vacuum to complete the vacuum switch. In some embodiments of the present invention, a metal cover can be used in place of the trigger electrode on the substrate. Materials used for the vacuum switch are compatible with high vacuum, relatively high temperature processing. These materials include molybdenum, niobium, copper, tungsten, aluminum and alloys thereof for the anode and cathode. Carbon in the form of graphitic carbon, a diamond-like material, or carbon nanotubes can be used in the trigger electrode. Channels can be optionally formed in the substrate to mitigate against surface breakdown.

  15. Trigger and decision processors

    International Nuclear Information System (INIS)

    Franke, G.

    1980-11-01

    In recent years there have been many attempts in high energy physics to make trigger and decision processes faster and more sophisticated. This became necessary due to a permanent increase of the number of sensitive detector elements in wire chambers and calorimeters, and in fact it was possible because of the fast developments in integrated circuits technique. In this paper the present situation will be reviewed. The discussion will be mainly focussed upon event filtering by pure software methods and - rather hardware related - microprogrammable processors as well as random access memory triggers. (orig.)

  16. ALICE High Level Trigger

    CERN Multimedia

    Alt, T

    2013-01-01

    The ALICE High Level Trigger (HLT) is a computing farm designed and build for the real-time, online processing of the raw data produced by the ALICE detectors. Events are fully reconstructed from the raw data, analyzed and compressed. The analysis summary together with the compressed data and a trigger decision is sent to the DAQ. In addition the reconstruction of the events allows for on-line monitoring of physical observables and this information is provided to the Data Quality Monitor (DQM). The HLT can process event rates of up to 2 kHz for proton-proton and 200 Hz for Pb-Pb central collisions.

  17. Catalyst for hydrocarbon conversion

    International Nuclear Information System (INIS)

    Duhaut, P.; Miquel, J.

    1975-01-01

    A description is given for a catalyst and process for hydrocarbon conversions, e.g., reforming. The catalyst contains an alumina carrier, platinum, iridium, at least one metal selected from uranium, vanadium, and gallium, and optionally halogen in the form of metal halide of one of the aforesaid components. (U.S.)

  18. Palladium-catalysed arylation of acetoacetate esters to yield 2-arylacetic acid esters

    CSIR Research Space (South Africa)

    Zeevaart, JG

    2004-05-24

    Full Text Available The coupling reaction between ethyl acetoacetate and a number of aryl halides in the presence of palladium acetate, a bulky and electron rich phosphine and K3PO4 is described. The arylated acetoacetate ester is de-acylated under the reaction...

  19. Unprecedentedly mild direct Pd-catalyzed arylation of oxazolo[4,5-b]pyridine

    DEFF Research Database (Denmark)

    Zhuravlev, Fedor

    2006-01-01

    Pd-catalyzed C-2 arylation of oxazolo[4,5-b]pyridine proceeds efficiently at 30 degrees C and tolerates a variety of aryl halides, including derivatized amino acids for which no racemization was observed during the reaction. Experimental evidence for facile deprotonation of oxazolo[4,5-b...

  20. Catalytic membrane-installed microchannel reactors for one-second allylic arylation.

    Science.gov (United States)

    Yamada, Yoichi M A; Watanabe, Toshihiro; Torii, Kaoru; Uozumi, Yasuhiro

    2009-10-07

    A variety of catalytic membranes of palladium-complexes with linear polymer ligands were prepared inside a microchannel reactor via coordinative and ionic molecular convolution to provide catalytic membrane-installed microdevices, which were applied to the instantaneous allylic arylation reaction of allylic esters and aryl boron reagents under microflow conditions to afford the corresponding coupling products within 1 second of residence time.

  1. Copper-catalyzed one-pot synthesis of N-aryl oxazolidinones from amino alcohol carbamates.

    Science.gov (United States)

    Mahy, William; Plucinski, Pawel K; Frost, Christopher G

    2014-10-03

    An efficient sequential intramolecular cyclization of amino alcohol carbamates followed by Cu-catalyzed cross-coupling with aryl iodides under mild conditions has been developed. The reaction occurred in good yields and tolerated aryl iodides containing functionalities such as nitriles, ketones, ethers, and halogens. Heteroaryl iodides and substituted amino alcohol carbamates were also well tolerated.

  2. Copper-(s)-N-methylpyrrolidine-2-carboxylate catalyzed N-Arylation ...

    African Journals Online (AJOL)

    copper-catalyzed N-arylation of N5H-1,2,5-thiadiazolidine 1,1-dioxides derivatives (cyclic sulfamides) is described. Reactions were carried out using Ullmann–Goldberg-type condensation with (S)-N-methyl- 2-carboxylate as the ligand, and N-arylated products were obtained with moderate to good yields. The structures of ...

  3. Catalyst free, base free microwave irradiated synthesis of aryl nitrites from potassium aryltrifluoroborates and bismuth nitrate

    Science.gov (United States)

    Al-Masum, Mohammad; Welch, Rebecca L.

    2014-01-01

    A mixture of bismuth nitrate pentahydrate and potassium aryltrifluoroborate in toluene under microwave heating at 120 °C for 20 min provides an interesting and mild reaction protocol for the synthesis of aryl nitrite. The conversion to aryl nitrites from aryltrifluoroborates without transition metal catalyst and base in high yields is remarkable. PMID:25242828

  4. Practical catalytic arylation of C–H bonds by iron/phenanthroline systems

    NARCIS (Netherlands)

    Huang, Y.

    2015-01-01

    In Chapter 1, an overview is given of the current status of the field of non-precious metal catalyzed/mediated direct arylation reactions. Reports on direct arylations catalyzed by Fe, Co, Ni and Cu are mainly demonstrated and discussed. Chapter 2 described a pre-made iron-based catalytic system

  5. Palladium-Catalyzed C–H Arylation of 1,2,3-Triazoles

    Science.gov (United States)

    Zhang, Chengwei; You, Lin; Chen, Chuo

    2016-01-01

    Palladium(II) acetate, in combination with triphenylphosphine, catalyzes direct arylation of 1,4-disubstituted 1,2,3-triazoles effectively. This C–H arylation reaction provides facile access to fully substituted triazoles with well-defined regiochemistry. PMID:27669198

  6. Regioselective iodination of aryl amines using 1,4-dibenzyl-1,4 ...

    African Journals Online (AJOL)

    1,4-Dibenzyl-1,4-diazoniabicyclo[2.2.2]octane dichloroiodate is an efficient and regioselective reagent for iodination of aryl amines. A wide variety of aryl amines in reaction with this reagent afforded regioselectively iodinated products. The iodination reaction can be carried out in solution or under solvent-free condition at ...

  7. Oxidative addition of aryl chlorides to monoligated palladium(0): A DFT-SCRF study

    DEFF Research Database (Denmark)

    Ahlquist, Mårten Sten Gösta; Norrby, Per-Ola

    2007-01-01

    Oxidative addition of aryl chlorides to palladium has been investigated by hybrid density functional theory methods (B3LYP), including a continuum model describing the solvent implicitly. A series of para-substituted aryl chlorides were studied to see the influence of electronic effects on the re...

  8. Triggering in Thermoacoustics

    Directory of Open Access Journals (Sweden)

    Matthew P. Juniper

    2012-09-01

    Full Text Available Under certain conditions, the flow in a combustion chamber can sustain large amplitude oscillations even when its steady state is linearly stable. Experimental studies show that these large oscillations can sometimes be triggered by very low levels of background noise. This theoretical paper sets out the conditions that are necessary for triggering to occur. It uses a weakly nonlinear analysis to show when these conditions will be satisfied for cases where the heat release rate is a function of the acoustic velocity. The role played by non-normality is investigated. It is shown that, when a state triggers to sustained oscillations from the lowest possible energy, it exploits transient energy growth around an unstable limit cycle. The positions of these limit cycles in state space is determined by nonlinearity, but the tangled-ness of trajectories in state space is determined by non-normality. When viewed in this dynamical systems framework, triggering in thermoacoustics is seen to be directly analogous to bypass transition to turbulence in pipe flow.

  9. Solated Muon Trigger

    CERN Document Server

    Albajar, Carmen

    2000-01-01

    An Isolated Muon L1 Trigger is proposed to reject muons from decays of b and c-quarks preserving high efficiency for muons from heavier objects. It is shown that the proposed algorithm is feasible and significant rejection factor ( 3-10) can be achieved. Similar algorithm can be applied at L2.

  10. Dealing with Asthma Triggers

    Science.gov (United States)

    ... one trigger that you shouldn't avoid because exercise is important for your health. Your doctor will want you to be active, so talk with him or her about what to do before playing ... or 15 minutes before you exercise or play sports. And, of course, you'll ...

  11. A New Method for Production of Chiral 2-Aryl-2-fluoropropanoic Acids Using an Effective Kinetic Resolution of Racemic 2-Aryl-2-fluoropropanoic Acids

    Directory of Open Access Journals (Sweden)

    Atsushi Tengeiji

    2012-06-01

    Full Text Available We report a new method for the preparation of chiral 2-aryl-2-fluoropropanoic acids, including 2-fluoroibuprofen, a fluorinated analogue of non-steroidal anti-inflammatory drugs (NSAIDs, by the kinetic resolution of racemic 2-aryl-2-fluoropropanoic acids using enantioselective esterification. By applying pivalic anhydride (Piv2O as a coupling agent, bis(α-naphthylmethanol [(α-Np2CHOH] as an achiral alcohol, and (+-benzotetramisole (BTM as a chiral acyl-transfer catalyst, a series of racemic 2-aryl-2-fluoropropanoic acids were kinetically separated to afford the optically active carboxylic acids and the corresponding esters with good to high enantiomeric excesses. This technology can provide a convenient approach to furnish the chiral α-fluorinated drugs containing quaternary carbons at the α-positions in the 2-aryl-2-fluoropropanoic acid structure.

  12. The Enantioselective α-Arylation of Aldehydes via Organo-SOMO Catalysis. An Ortho-Selective Arylation Reaction Based on an Open-Shell Pathway

    Science.gov (United States)

    Conrad, Jay C.; Kong, Jongrock; Laforteza, Brian N.

    2009-01-01

    The intramolecular α-arylation of aldehydes has been accomplished using singly occupied molecular orbital (SOMO) catalysis. Selective oxidation of chiral enamines (formed by the condensation of an aldehyde and a secondary amine catalyst) leads to the formation of a 3π-electron radical species. These chiral SOMO-activated radical cations undergo enantioselective reaction with an array of pendent electron-rich aromatics and heterocycles thus efficiently providing cyclic α-aryl aldehyde products (10 examples: ≥70% yield and ≥90% ee). In accordance with our radical mechanism, when there is a choice between arylation at the ortho or para position of anisole substrates, we find that arylation proceeds selectively at the ortho position. PMID:19639997

  13. Influence of Functionality on Direct Arylation of Model Systems as a Route Toward Fluorinated Copolymers via Direct Arylation Polymerization (DArP)

    DEFF Research Database (Denmark)

    Livi, Francesco; Gobalasingham, Nemal S.; Bundgaard, Eva

    2015-01-01

    . Themodel system features a coupling between a 2-substituted thiopheneand a pentafluorobenzene, where one of the partnerswas brominated. A substantial difference in reactivity isobserved, demonstrating that the optimal functionalization fordirect arylation between a thiophene-based donor...

  14. Manganese-Catalyzed Cross-Coupling of Aryl Halides and Grignard Reagents by a Radical Mechanism

    DEFF Research Database (Denmark)

    Antonacci, Giuseppe; Ahlburg, Andreas; Fristrup, Peter

    2017-01-01

    The substrate scope and the mechanism have been investigated for the MnCl2-catalyzed cross-coupling reaction between aryl halides and Grignard reagents. The transformation proceeds rapidly and in good yield when the aryl halide component is an aryl chloride containing a cyano or an ester group...... in the para position or a cyano group in the ortho position. A range of other substituents gave no conversion of the aryl halide or led to the formation of side products. A broader scope was observed for the Grignard reagents, where a variety of alkyl- and arylmagnesium chlorides participated in the coupling....... Two radical-clock experiments were carried out, and in both cases an intermediate aryl radical was successfully trapped. The cross-coupling reaction is therefore believed to proceed by an SRN1 mechanism, with a triorganomanganate complex serving as the most likely nucleophile and single-electron donor...

  15. Organocatalysis in cross-coupling: DMEDA-catalyzed direct C-H arylation of unactivated benzene.

    Science.gov (United States)

    Liu, Wei; Cao, Hao; Zhang, Hua; Zhang, Heng; Chung, Kin Ho; He, Chuan; Wang, Haibo; Kwong, Fuk Yee; Lei, Aiwen

    2010-12-01

    A striking breakthrough to the frame of traditional cross-couplings/C-H functionalizations using an organocatalyst remains unprecedented. We uncovered a conceptually different approach toward the biaryl syntheses by using DMEDA as the catalyst to promote the direct C-H arylation of unactivated benzene in the presence of potassium tert-butoxide. The arylation of unactivated benzene with aryl iodides, or aryl bromides and even chlorides under the assistance of an iodo-group, could simply take place at 80 °C. The new methodology presumably involves an aryl radical anion as an intermediate. This finding offers an option toward establishing a new horizon for direct C-H/cross-coupling reactions.

  16. Systematic investigations on the reduction of 4-aryl-4-oxoesters to 1-aryl-1,4-butanediols with methanolic sodium borohydride

    Directory of Open Access Journals (Sweden)

    Subrata Kumar Chaudhuri

    2010-09-01

    Full Text Available 4-Aryl-4-oxoesters undergo facile reduction of both the keto and the ester groups with methanolic NaBH4 at room temperature to yield the corresponding 1-aryl-1,4-butanediols whereas 4-alkyl-4-oxoesters furnish the corresponding 1,4-butanolides via selective reduction of the keto moiety. Results of a detailed and systematic investigation of the reaction are described.

  17. Reactivity of bromoselenophenes in palladium-catalyzed direct arylations

    Directory of Open Access Journals (Sweden)

    Aymen Skhiri

    2017-12-01

    Full Text Available The reactivity of 2-bromo- and 2,5-dibromoselenophenes in Pd-catalyzed direct heteroarylation was investigated. From 2-bromoselenophene, only the most reactive heteroarenes could be employed to prepare 2-heteroarylated selenophenes; whereas, 2,5-dibromoselenophene generally gave 2,5-di(heteroarylated selenophenes in high yields using both thiazole and thiophene derivatives. Moreover, sequential catalytic C2 heteroarylation, bromination, catalytic C5 arylation reactions allowed the synthesis of unsymmetrical 2,5-di(heteroarylated selenophene derivatives in three steps from selenophene.

  18. A well-defined (POCOP)Rh catalyst for the coupling of aryl halides with thiols.

    Science.gov (United States)

    Timpa, Samuel D; Pell, Christopher J; Ozerov, Oleg V

    2014-10-22

    This article describes a well-defined pincer-Rh catalyst for C-S cross-coupling reactions. (POCOP)Rh(H)(Cl) serves as an active precatalyst for the coupling of aryl chlorides and bromides with aryl and alkyl thiols under reasonable conditions (3% mol cat., 110 °C, 2-24 h, >90% yield). For select substrates, >90% yields were obtained with catalyst loading as low as 0.1%. Key mechanistic intermediates have been isolated and fully characterized, including (POCOP)Rh(Ph)(SPh) (6a) and (POCOP)Rh(SPh2) (6b). The aryl/bis(phosphinite) (POCOP)Rh system has been shown to favor aryl thiolate reductive elimination at elevated temperatures and in some cases at room temperature, compared with the analogous diarylamido/bis(phosphine) (PNP)Rh pincer system. Concerted reductive elimination has been studied with 6a directly and in the presence of aryl bromide and aryl chloride traps. This investigation demonstrates a clear rate dependence on aryl chloride concentration during catalysis, a dependence that is absent when using aryl bromides. The rate of catalysis is dramatically reduced or brought to zero for ortho-tolyl halides, which can be traced to slower C-S coupling and slower carbon-halogen oxidative addition for ortho-substituted aryls. The influence of the sterics in the thiol component is less straightforward. The S-H oxidative addition product (POCOP)Rh(H)(SPh) (16) has been fully characterized and its reactivity has been examined, resulting in the isolation of the sodium-thiolate adduct (POCOP)Rh(NaSPh) (19). The solid-state structure of 19 shows Na interactions not only with sulfur, but also with a neighboring Rh and the chelating aryl carbon of the pincer framework. The reactivity of 16 and 19 indicates that these potential side products should not hinder catalysis.

  19. Superconductivity in aromatic hydrocarbons

    Energy Technology Data Exchange (ETDEWEB)

    Kubozono, Yoshihiro, E-mail: kubozono@cc.okayama-u.ac.jp [Research Laboratory for Surface Science, Okayama University, Okayama 700-8530 (Japan); Research Center of New Functional Materials for Energy Production, Storage and Transport, Okayama University, Okayama 700-8530 (Japan); Japan Science and Technology Agency, ACT-C, Kawaguchi 332-0012 (Japan); Goto, Hidenori; Jabuchi, Taihei [Research Laboratory for Surface Science, Okayama University, Okayama 700-8530 (Japan); Yokoya, Takayoshi [Research Laboratory for Surface Science, Okayama University, Okayama 700-8530 (Japan); Research Center of New Functional Materials for Energy Production, Storage and Transport, Okayama University, Okayama 700-8530 (Japan); Kambe, Takashi [Department of Physics, Okayama University, Okayama 700-8530 (Japan); Sakai, Yusuke; Izumi, Masanari; Zheng, Lu; Hamao, Shino; Nguyen, Huyen L.T. [Research Laboratory for Surface Science, Okayama University, Okayama 700-8530 (Japan); Sakata, Masafumi; Kagayama, Tomoko; Shimizu, Katsuya [Center of Science and Technology under Extreme Conditions, Osaka University, Osaka 560-8531 (Japan)

    2015-07-15

    Highlights: • Aromatic superconductor is one of core research subjects in superconductivity. Superconductivity is observed in certain metal-doped aromatic hydrocarbons. Some serious problems to be solved exist for future advancement of the research. This article shows the present status of aromatic superconductors. - Abstract: ‘Aromatic hydrocarbon’ implies an organic molecule that satisfies the (4n + 2) π-electron rule and consists of benzene rings. Doping solid aromatic hydrocarbons with metals provides the superconductivity. The first discovery of such superconductivity was made for K-doped picene (K{sub x}picene, five benzene rings). Its superconducting transition temperatures (T{sub c}’s) were 7 and 18 K. Recently, we found a new superconducting K{sub x}picene phase with a T{sub c} as high as 14 K, so we now know that K{sub x}picene possesses multiple superconducting phases. Besides K{sub x}picene, we discovered new superconductors such as Rb{sub x}picene and Ca{sub x}picene. A most serious problem is that the shielding fraction is ⩽15% for K{sub x}picene and Rb{sub x}picene, and it is often ∼1% for other superconductors. Such low shielding fractions have made it difficult to determine the crystal structures of superconducting phases. Nevertheless, many research groups have expended a great deal of effort to make high quality hydrocarbon superconductors in the five years since the discovery of hydrocarbon superconductivity. At the present stage, superconductivity is observed in certain metal-doped aromatic hydrocarbons (picene, phenanthrene and dibenzopentacene), but the shielding fraction remains stubbornly low. The highest priority research area is to prepare aromatic superconductors with a high superconducting volume-fraction. Despite these difficulties, aromatic superconductivity is still a core research target and presents interesting and potentially breakthrough challenges, such as the positive pressure dependence of T{sub c} that is clearly

  20. The ATLAS Tau Trigger

    International Nuclear Information System (INIS)

    Rados, Petar Kevin

    2013-06-01

    The tau lepton plays a crucial role in understanding particle physics at the Tera scale. One of the most promising probes of the Higgs boson coupling to fermions is with detector signatures involving taus. In addition, many theories beyond the Standard Model, such as supersymmetry and exotic particles (W' and Z'), predict new physics with large couplings to taus. The ability to trigger on hadronic tau decays is therefore critical to achieving the physics goals of the ATLAS experiment. The higher instantaneous luminosities of proton-proton collisions achieved by the Large Hadron Collider (LHC) in 2012 resulted in a larger probability of overlap (pile-up) between bunch crossings, and so it was critical for ATLAS to have an effective tau trigger strategy. The details of this strategy are summarized in this paper, and the results of the latest performance measurements are presented. (authors)

  1. Minimum risk trigger indices

    International Nuclear Information System (INIS)

    Tingey, F.H.

    1979-01-01

    A viable safeguards system includes among other things the development and use of indices which trigger various courses of action. The usual limit of error calculation provides such an index. The classical approach is one of constructing tests which, under certain assumptions, make the likelihood of a false alarm small. Of concern also is the test's failure to indicate a loss (diversion) when in fact one has occurred. Since false alarms are usually costly and losses both costly and of extreme strategic sinificance, there remains the task of balancing the probability of false alarm and its consequences against the probability of undetected loss and its consequences. The application of other than classical hypothesis testing procedures are considered in this paper. Using various consequence models, trigger indices are derived which have certain optimum properties. Application of the techniques would enhance the material control function

  2. The LPS trigger system

    International Nuclear Information System (INIS)

    Benotto, F.; Costa, M.; Staiano, A.; Zampieri, A.; Bollito, M.; Isoardi, P.; Pernigotti, E.; Sacchi, R.; Trapani, P.P.; Larsen, H.; Massam, T.; Nemoz, C.

    1996-03-01

    The Leading Proton Spectrometer (LPS) has been equipped with microstrip silicon detectors specially designed to trigger events with high values of x L vertical stroke anti p' p vertical stroke / vertical stroke anti p p vertical stroke ≥0.95 where vertical stroke anti p' p vertical stroke and vertical stroke anti p p vertical stroke are respectively the momenta of outgoing and incoming protons. The LPS First Level Trigger can provide a clear tag for very high momentum protons in a kinematical region never explored before. In the following we discuss the physics motivation in tagging very forward protons and present a detailed description of the detector design, the front end electronics, the readout electronics, the Monte Carlo simulation and some preliminary results from 1995 data taking. (orig.)

  3. Direct hydrocarbon fuel cells

    Science.gov (United States)

    Barnett, Scott A.; Lai, Tammy; Liu, Jiang

    2010-05-04

    The direct electrochemical oxidation of hydrocarbons in solid oxide fuel cells, to generate greater power densities at lower temperatures without carbon deposition. The performance obtained is comparable to that of fuel cells used for hydrogen, and is achieved by using novel anode composites at low operating temperatures. Such solid oxide fuel cells, regardless of fuel source or operation, can be configured advantageously using the structural geometries of this invention.

  4. GLAST's GBM Burst Trigger

    Science.gov (United States)

    Band, D.; Briggs, M.; Connaughton, V.; Kippen, M.; Preece, R.

    2003-01-01

    The GLAST Burst Monitor (GBM) will detect and localize bursts for the GLAST mission, and provide the spectral and temporal context in the traditional 10 keV to 25 MeV band for the high energy observations by the Large Area Telescope (LAT). The GBM will use traditional rate triggers in up to three energy bands, and on a variety of timescales between 16 ms and 16 s.

  5. The ARGUS vertex trigger

    International Nuclear Information System (INIS)

    Koch, N.; Kolander, M.; Kolanoski, H.; Siegmund, T.; Bergter, J.; Eckstein, P.; Schubert, K.R.; Waldi, R.; Imhof, M.; Ressing, D.; Weiss, U.; Weseler, S.

    1995-09-01

    A fast second level trigger has been developed for the ARGUS experiment which recognizes tracks originating from the interaction region. The processor compares the hits in the ARGUS Micro Vertex Drift Chamber to 245760 masks stored in random access memories. The masks which are fully defined in three dimensions are able to reject tracks originating in the wall of the narrow beampipe of 10.5 mm radius. (orig.)

  6. Neural networks for triggering

    International Nuclear Information System (INIS)

    Denby, B.; Campbell, M.; Bedeschi, F.; Chriss, N.; Bowers, C.; Nesti, F.

    1990-01-01

    Two types of neural network beauty trigger architectures, based on identification of electrons in jets and recognition of secondary vertices, have been simulated in the environment of the Fermilab CDF experiment. The efficiencies for B's and rejection of background obtained are encouraging. If hardware tests are successful, the electron identification architecture will be tested in the 1991 run of CDF. 10 refs., 5 figs., 1 tab

  7. Physics issues on triggering

    Indian Academy of Sciences (India)

    The detector at the international linear collider (ILC) should be able to run 'trig- gerless' which means that all events can be read out and then be analysed with the offline reconstruction program in a trigger farm. The event rates for 'high Q2' events like W-pairs or q¯q are low, about 0.1/train. However, there is a significant.

  8. Aryl Diazonium Chemistry for the Surface Functionalization of Glassy Biosensors

    Directory of Open Access Journals (Sweden)

    Wei Zheng

    2016-03-01

    Full Text Available Nanostring resonator and fiber-optics-based biosensors are of interest as they offer high sensitivity, real-time measurements and the ability to integrate with electronics. However, these devices are somewhat impaired by issues related to surface modification. Both nanostring resonators and photonic sensors employ glassy materials, which are incompatible with electrochemistry. A surface chemistry approach providing strong and stable adhesion to glassy surfaces is thus required. In this work, a diazonium salt induced aryl film grafting process is employed to modify a novel SiCN glassy material. Sandwich rabbit IgG binding assays are performed on the diazonium treated SiCN surfaces. Fluorescently labelled anti-rabbit IgG and anti-rabbit IgG conjugated gold nanoparticles were used as markers to demonstrate the absorption of anti-rabbit IgG and therefore verify the successful grafting of the aryl film. The results of the experiments support the effectiveness of diazonium chemistry for the surface functionalization of SiCN surfaces. This method is applicable to other types of glassy materials and potentially can be expanded to various nanomechanical and optical biosensors.

  9. Aryl Diazonium Chemistry for the Surface Functionalization of Glassy Biosensors

    Science.gov (United States)

    Zheng, Wei; van den Hurk, Remko; Cao, Yong; Du, Rongbing; Sun, Xuejun; Wang, Yiyu; McDermott, Mark T.; Evoy, Stephane

    2016-01-01

    Nanostring resonator and fiber-optics-based biosensors are of interest as they offer high sensitivity, real-time measurements and the ability to integrate with electronics. However, these devices are somewhat impaired by issues related to surface modification. Both nanostring resonators and photonic sensors employ glassy materials, which are incompatible with electrochemistry. A surface chemistry approach providing strong and stable adhesion to glassy surfaces is thus required. In this work, a diazonium salt induced aryl film grafting process is employed to modify a novel SiCN glassy material. Sandwich rabbit IgG binding assays are performed on the diazonium treated SiCN surfaces. Fluorescently labelled anti-rabbit IgG and anti-rabbit IgG conjugated gold nanoparticles were used as markers to demonstrate the absorption of anti-rabbit IgG and therefore verify the successful grafting of the aryl film. The results of the experiments support the effectiveness of diazonium chemistry for the surface functionalization of SiCN surfaces. This method is applicable to other types of glassy materials and potentially can be expanded to various nanomechanical and optical biosensors. PMID:26985910

  10. Direct arylation and heterogeneous catalysis; ever the twain shall meet

    Science.gov (United States)

    Cano, Rafael

    2015-01-01

    The formation of aryl–aryl bonds and heteroaryl analogues is one of the most important C–C bond forming processes in organic chemistry. Recently, a methodology termed Direct Arylation (DA) has emerged as an attractive alternative to traditional cross-coupling reactions (Suzuki–Miyaura, Stille, Negishi, etc.). A parallel focus of the pharmaceutical and other chemical industries has been on the use heterogeneous catalysis as a favourable substitute for its homogeneous counterpart in cross-coupling reactions. Only very recently has heterogeneous catalysis been proposed and applied, to DA reactions. In this perspective, we consider the terms ‘heterogeneous’ and ‘homogeneous’ and the problems associated with their delineation in transition-metal catalysed reactions. We highlight the reports at the interface of DA and heterogeneous catalysis and we comment briefly on the methods used which attempt to classify reaction types as homo- or heterogeneous. In future work we recommend an emphasis be placed on kinetic methods which provide an excellent platform for analysis. In addition two analytical techniques are described which if developed to run in situ with DA reactions would illuminate our understanding of the catalysis. Overall, we provide an entry point, and bring together the mature, yet poorly-understood, subject of heterogeneous catalysis with the rapidly expanding area of DA, with a view towards the acceleration of catalyst design and the understanding of catalyst behaviour. PMID:28717441

  11. Steric Effects in the Reaction of Aryl Radicals on Surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Combellas, Catherine [CNRS-ESPCI; Jiang, Deen [ORNL; Kanoufi, Frederic [CNRS-ESPCI; Pinson, Jean [Alchimer; Podvorica, Fetah [University of Prishtina, Kosovo

    2009-01-01

    Steric effects are investigated in the reaction of aryl radicals with surfaces. The electrochemical reduction of 2-, 3-, 4-methyl, 2-methoxy, 2-ethyl, 2,6-, 2,4-, and 3,5-dimethyl, 4-tert-butyl, 3,5-bis-tert-butyl benzenediazonium, 3,5-bis(trifluoromethyl), and pentafluoro benzenediazonium tetrafluoroborates is examined in acetonitrile solutions. It leads to the formation of grafted layers only if the steric hindrance at the 2- or 2,6-position(s) is small. When the 3,5-positions are crowded with tert-butyl groups, the growth of the organic layer is limited by steric effects and a monolayer is formed. The efficiency of the grafting process is assessed by cyclic voltammetry, X-ray photoelectron spectroscopy, infrared, and ellipsometry. These experiments, together with density functional computations of bonding energies of substituted phenyl groups on a copper surface, are discussed in terms of the reactivity of aryl radicals in the electrografting reaction and in the growth of the polyaryl layer.

  12. Aryl Diazonium Chemistry for the Surface Functionalization of Glassy Biosensors.

    Science.gov (United States)

    Zheng, Wei; van den Hurk, Remko; Cao, Yong; Du, Rongbing; Sun, Xuejun; Wang, Yiyu; McDermott, Mark T; Evoy, Stephane

    2016-03-14

    Nanostring resonator and fiber-optics-based biosensors are of interest as they offer high sensitivity, real-time measurements and the ability to integrate with electronics. However, these devices are somewhat impaired by issues related to surface modification. Both nanostring resonators and photonic sensors employ glassy materials, which are incompatible with electrochemistry. A surface chemistry approach providing strong and stable adhesion to glassy surfaces is thus required. In this work, a diazonium salt induced aryl film grafting process is employed to modify a novel SiCN glassy material. Sandwich rabbit IgG binding assays are performed on the diazonium treated SiCN surfaces. Fluorescently labelled anti-rabbit IgG and anti-rabbit IgG conjugated gold nanoparticles were used as markers to demonstrate the absorption of anti-rabbit IgG and therefore verify the successful grafting of the aryl film. The results of the experiments support the effectiveness of diazonium chemistry for the surface functionalization of SiCN surfaces. This method is applicable to other types of glassy materials and potentially can be expanded to various nanomechanical and optical biosensors.

  13. Catalytic arylation methods from the academic lab to industrial processes

    CERN Document Server

    Burke, Anthony J

    2014-01-01

    This "hands-on" approach to the topic of arylation consolidates the body of key research over the last ten years (and up to around 2014) on various catalytic methods which involve an arylation process. Clearly structured, the chapters in this one-stop resource are arranged according to the reaction type, and focus on novel, efficient and sustainable processes, rather than the well-known and established cross-coupling methods. The entire contents are written by two authors with academic and industrial expertise to ensure consistent coverage of the latest developments in the field, as well as industrial applications, such as C-H activation, iron and gold-catalyzed coupling reactions, cycloadditions or novel methodologies using arylboron reagents. A cross-section of relevant tried-and-tested experimental protocols is included at the end of each chapter for putting into immediate practice, along with patent literature. Due to its emphasis on efficient, "green" methods and industrial applications of the products c...

  14. Well-Defined Copper(I) Fluoroalkoxide Complexes for Trifluoroethoxylation of Aryl and Heteroaryl Bromides

    KAUST Repository

    Huang, Ronglu

    2015-03-17

    © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Copper(I) fluoroalkoxide complexes bearing dinitrogen ligands were synthesized and the structure and reactivity of the complexes toward trifluoroethoxylation, pentafluoropropoxylation, and tetrafluoropropoxylation of aryl and heteroaryl bromides were investigated. Efficiency drive: A series of copper(I) fluoroalkoxide complexes bearing N,N ligands have been prepared and structurally characterized. These well-defined complexes serve as efficient reagents for the fluoroalkoxylation of aryl and heteroaryl bromides to produce a wide range of trifluoroethyl, pentafluoropropyl, and tetrafluoropropyl (hetero)aryl ethers in good to excellent yields.

  15. Reactivity of Aryl Halides for Reductive Dehalogenation in (Seawater Using Polymer-Supported Terpyridine Palladium Catalyst

    Directory of Open Access Journals (Sweden)

    Toshimasa Suzuka

    2015-05-01

    Full Text Available A polymer-supported terpyridine palladium complex was prepared. The complex was found to promote hydrodechlorination of aryl chlorides with potassium formate in seawater. Generally, reductive cleavage of aryl chlorides using transition metal catalysts is more difficult than that of aryl bromides and iodides (reactivity: I > Br > Cl; however, the results obtained did not follow the general trend. Therefore, we investigated the reaction inhibition agents and found a method to remove these inhibitors. The polymeric catalysts showed high catalytic activity and high reusability for transfer reduction in seawater.

  16. Microwave-assisted synthesis of α-aryl malonates: Key intermediates for the

    Directory of Open Access Journals (Sweden)

    Mohamed A. Ibrahim

    2016-11-01

    Full Text Available We disclose a new microwave-assisted protocol for the effective α-arylation of diethyl malonate. The coupling of aryl halides with diethyl malonate proceeds smoothly in short reaction time in the presence of a catalytic amount of Cu(OTf2, 2-picolinic acid and Cs2CO3 in toluene using microwave irradiation. The resulting α-aryl malonates are then used as key intermediates for synthesis of variety of heterocyclic compounds, including benzodiazepines, isoquinolines and pyrrolopyridine scaffolds.

  17. Unusual selectivity-determining factors in the phosphine-free Heck arylation of allyl ethers

    DEFF Research Database (Denmark)

    Ambrogio, I.; Fabrizi, G.; Cacchi, S.

    2008-01-01

    The Heck reaction of aryl iodides and bromides with allyl ethers has been investigated. Using phosphinefree Pd(OAc)(2) in DNIF at 90 degrees C in the presence of Bu4NOAc, the reaction gave cinnamyl derivatives, usually in good to high yields, with a wide range of aryl halides. The reaction...... tolerates a variety of functional groups, including ether, amide, alcohol, aldehyde, ketone, ester, cyano, carboxylic acid, and nitro groups. Ortho-substituted arylating agents afforded moderate yields in some cases, though good to high yields were obtained with o-iodotoluene, iodovanillin, and 1...

  18. Synthesis, Antibacterial and Antifungal Activity of 4-Substituted-5-Aryl-1,2,4-Triazoles

    Directory of Open Access Journals (Sweden)

    Aleksandra Buzarovska

    2001-09-01

    Full Text Available A few 4-allyl/amino-5-aryl-1,2,4-triazoles were synthesized and tested for antibacterial and antifungal effects against Escherichia coli, Bacillus subtilis, Salmonella enteritidis, Staphylococcus aureus, Aspergillus niger and Candida albicans. 4-Allyl-5-aryl-1,2,4-triazoles were obtained by the oxidative cyclization of the appropriate 1-substituted-4-allylthiosemicarbazides and 4-amino-5-aryl-1,2,4-triazoles were obtained by cyclization of the potassium salts of appropriately substituted dithiocarbazinic acids with hydrazine hydrate. The new synthesized compounds were characterized using IR, 1H- NMR, 13C-NMR and UV spectral data together with elemental analysis.

  19. One-pot synthesis of aryl sulfones from organometallic reagents and iodonium salts.

    Science.gov (United States)

    Margraf, Natalie; Manolikakes, Georg

    2015-03-06

    A transition-metal-free arylation of lithium, magnesium, and zinc sulfinates with diaryliodonium salts is described. The sulfinic acid salts were prepared from the reaction of the corresponding organometallic reagents and sulfur dioxide. Combination of the three single steps (preparation of the organometallic compound, sulfinate formation, and arylation) leads to a one-pot sequence for the synthesis of aryl sulfones from simple starting materials. The chemoselectivity of unsymmetrical diaryliodonium salts has been investigated. Potential and limitations of this method will be discussed.

  20. ATLAS Tau Trigger

    CERN Document Server

    Belanger-Champagne, C; Bosman, M; Brenner, R; Casado, MP; Czyczula, Z; Dam, M; Demers, S; Farrington, S; Igonkina, O; Kalinowski, A; Kanaya, N; Osuna, C; Pérez, E; Ptacek, E; Reinsch, A; Saavedra, A; Sopczak, A; Strom, D; Torrence, E; Tsuno, S; Vorwerk, V; Watson, A; Xella, S

    2008-01-01

    Moving to the high energy scale of the LHC, the identification of tau leptons will become a necessary and very powerful tool, allowing a discovery of physics beyond Standard Model. Many models, among them light SM Higgs and various SUSY models, predict an abundant production of taus with respect to other leptons. The reconstruction of hadronic tau decays, although a very challenging task in hadronic enviroments, allows to increase a signal efficiency by at least of factor 2, and provides an independent control sample to disantangle lepton tau decays from prompt electrons and muons. Thanks to the advanced calorimetry and tracking, the ATLAS experiment has developed tools to efficiently identify hadronic taus at the trigger level. In this presentation we will review the characteristics of taus and the methods to suppress low-multiplicity, low-energy jets contributions as well as we will address the tau trigger chain which provide a rejection rate of 10^5. We will further present plans for commissioning the ATLA...

  1. The nuclear aryl hydocarbon receptor is involved in regulation of DNA repair and cell survival following treatment with ionizing radiation.

    Science.gov (United States)

    Dittmann, K H; Rothmund, M C; Paasch, A; Mayer, C; Fehrenbacher, B; Schaller, M; Frauenstein, K; Fritsche, E; Haarmann-Stemmann, T; Braeuning, A; Rodemann, H P

    2016-01-05

    In the present study, we explored the role of the aryl hydrocarbon receptor (AhR) for γ-H2AX associated DNA repair in response to treatment with ionizing radiation. Ionizing radiation was able to stabilize AhR protein and to induce a nuclear translocation in a similar way as described for exposure to aromatic hydrocarbons. A comparable AhR protein stabilization was obtained by treatment with hydroxyl-nonenal-generated by radiation-induced lipid peroxidation. AhR knockdown resulted in significant radio-sensitization of both A549- and HaCaT cells. Under these conditions an increased amount of residual γ-H2AX foci and a delayed decline of γ-H2AX foci was observed. Knockdown of the co-activator ARNT, which is essential for transcriptional activation of AhR target genes, reduced AhR-dependent CYP1A expression in response to irradiation, but was without effect on the amount of residual γ-H2AX foci. Nuclear AhR was found in complex with γ-H2AX, DNA-PK, ATM and Lamin A. AhR and γ-H2AX form together nuclear foci, which disappear during DNA repair. Presence of nuclear AhR protein is associated with ATM activation and chromatin relaxation indicated by acetylation of histone H3. Taken together, we could show, that beyond the function as a transcription factor the nuclear AhR is involved in the regulation of DNA repair. Reduction of nuclear AhR inhibits DNA-double stand repair and radiosensitizes cells. First hints for its molecular mechanism suggest a role during ATM activation and chromatin relaxation, both essential for DNA repair. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. The D0 calorimeter trigger

    International Nuclear Information System (INIS)

    Guida, J.

    1992-12-01

    The D0 calorimeter trigger system consists of many levels to make physics motivated trigger decisions. The Level-1 trigger uses hardware techniques to reduce the trigger rate from ∼ 100kHz to 200Hz. It forms sums of electromagnetic and hadronic energy, globally and in towers, along with finding the missing transverse energy. A minimum energy is set on these energy sums to pass the event. The Level-2 trigger is a set of software filters, operating in a parallel-processing microvax farm which further reduces the trigger rate to a few Hertz. These filters will reject events which lack electron candidates, jet candidates, or missing transverse energy in the event. The performance of these triggers during the early running of the D0 detector will also be discussed

  3. Minimum Bias Trigger in ATLAS

    CERN Document Server

    Kwee, R E; The ATLAS collaboration

    2010-01-01

    Since the restart of the LHC in November 2009, ATLAS has collected inelastic pp-collisions to perform first measurements on charged particle densities. These measurements will help to constrain various models describing phenomenologically soft parton interactions. Understanding the trigger efficiencies for different event types are therefore crucial to minimize any possible bias in the event selection. ATLAS uses two main minimum bias triggers, featuring complementary detector components and trigger levels. While a hardware based first trigger level situated in the forward regions with 2.09 < |eta| < 3.8 has been proven to select pp-collisions very efficiently, the Inner Detector based minimum bias trigger uses a random seed on filled bunches and central tracking detectors for the event selection. Both triggers were essential for the analysis of kinematic spectra of charged particles. Their performance and trigger efficiency measurements as well as studies on possible bias sources will be presen...

  4. Discovery of novel N-aryl piperazine CXCR4 antagonists.

    Science.gov (United States)

    Zhao, Huanyu; Prosser, Anthony R; Liotta, Dennis C; Wilson, Lawrence J

    2015-11-01

    A novel series of CXCR4 antagonists with substituted piperazines as benzimidazole replacements is described. These compounds showed micromolar to nanomolar potency in CXCR4-mediated functional and HIV assays, namely inhibition of X4 HIV-1(IIIB) virus in MAGI-CCR5/CXCR4 cells and inhibition of SDF-1 induced calcium release in Chem-1 cells. Preliminary SAR investigations led to the identification of a series of N-aryl piperazines as the most potent compounds. Results show SAR that indicates type and position of the aromatic ring, as well as type of linker and stereochemistry are significant for activity. Profiling of several lead compounds showed that one (49b) reduced susceptibility towards CYP450 and hERG, and the best overall profile when considering both SDF-1 and HIV potencies (6-20 nM). Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Aryl Polyphosphonates: Useful Halogen-Free Flame Retardants for Polymers

    Directory of Open Access Journals (Sweden)

    Li Chen

    2010-10-01

    Full Text Available Aryl polyphosphonates (ArPPN have been demonstrated to function in wide applications as flame retardants for different polymer materials, including thermosets, polycarbonate, polyesters and polyamides, particularly due to their satisfactory thermal stability compared to aliphatic flame retardants, and to their desirable flow behavior observed during the processing of polymeric materials. This paper provides a brief overview of the main developments in ArPPN and their derivatives for flame-retarding polymeric materials, primarily based on the authors’ research work and the literature published over the last two decades. The synthetic chemistry of these compounds is discussed along with their thermal stabilities and flame-retardant properties. The possible mechanisms of ArPPN and their derivatives containing hetero elements, which exhibit a synergistic effect with phosphorus, are also discussed.

  6. Hydrocarbons: source of energy

    International Nuclear Information System (INIS)

    Imarisio, G.; Frias, M.; Bemtgen, J.M.

    1989-01-01

    Hydrocarbons are at present the single most important source of energy, since they are the most versatile and widely used. It is expected that their importance will extend well into the next century and therefore it is essential to provide for all those improvements which will extend their availability and usefulness. The sub-programme ''Optimization of the production and utilization of hydrocarbons'' (within the Non-Nuclear Energy R and D Programme of the European Communities) is pursuing a number of R and D topics aimed at the above-mentioned results. It is implemented by means of shared-cost R and D contracts. At this first Seminar held in Lyon (France) from 21-23 September, 1988, all contractors of the sub-programme presented the state of progress of their R and D projects. These proceedings comprise all the papers presented at the Seminar. The section on oilfield exploration includes a report of work on the interpretation of nuclear logs by means of mathematical models. (author)

  7. Bedford-type palladacycle catalyzed Miyaura-borylation of aryl halides with tetrahydroxydiboron in water

    KAUST Repository

    Zernickel, Anna

    2018-01-09

    A mild aqueous protocol for palladium catalyzed Miyaura borylation of aryl iodides, aryl bromides and aryl chlorides with tetrahydroxydiboron (BBA) as a borylating agent is developed. The developed methodology requires low catalyst loading of Bedford-type palladacycle catalyst (0.05 mol %) and works best under mild reaction conditions at 40 °C in short time of 6 hours in water. In addition, our studies show that for Miyaura borylation using BBA in aqueous condition, maintaining a neutral reaction pH is very important for reproducibility and higher yields of corresponding borylated products. Moreover, our protocol is applicable for a broad range of aryl halides, corresponding borylated products are obtained in excellent yields up to 93% with 29 examples demonstrating its broad utility and functional group tolerance.

  8. Induction of the p75NTR by Aryl Propionic Acids in Prostate Cancer Cells

    National Research Council Canada - National Science Library

    Quann, Emily

    2007-01-01

    .... I have found that treatment of prostate cancer cells with the aryl propionic acids R-flurbiprofen and ibuprofen induces reexpression of p75NTR, decreases cell survival, and increases apoptosis...

  9. Thermophysical Properties of Hydrocarbon Mixtures

    Science.gov (United States)

    SRD 4 NIST Thermophysical Properties of Hydrocarbon Mixtures (PC database for purchase)   Interactive computer program for predicting thermodynamic and transport properties of pure fluids and fluid mixtures containing up to 20 components. The components are selected from a database of 196 components, mostly hydrocarbons.

  10. Triggering at high luminosity: fake triggers from pile-up

    International Nuclear Information System (INIS)

    Johnson, R.

    1983-01-01

    Triggers based on a cut in transverse momentum (p/sub t/) have proved to be useful in high energy physics both because they indicte that a hard constituent scattering has occurred and because they can be made quickly enough to gate electronics. These triggers will continue to be useful at high luminosities if overlapping events do not cause an excessive number of fake triggers. In this paper, I determine if this is indeed a problem at high luminosity machines

  11. Nostalgia: content, triggers, functions.

    Science.gov (United States)

    Wildschut, Tim; Sedikides, Constantine; Arndt, Jamie; Routledge, Clay

    2006-11-01

    Seven methodologically diverse studies addressed 3 fundamental questions about nostalgia. Studies 1 and 2 examined the content of nostalgic experiences. Descriptions of nostalgic experiences typically featured the self as a protagonist in interactions with close others (e.g., friends) or in momentous events (e.g., weddings). Also, the descriptions contained more expressions of positive than negative affect and often depicted the redemption of negative life scenes by subsequent triumphs. Studies 3 and 4 examined triggers of nostalgia and revealed that nostalgia occurs in response to negative mood and the discrete affective state of loneliness. Studies 5, 6, and 7 investigated the functional utility of nostalgia and established that nostalgia bolsters social bonds, increases positive self-regard, and generates positive affect. These findings demarcate key landmarks in the hitherto uncharted research domain of nostalgia.

  12. Latent myofascial trigger points.

    Science.gov (United States)

    Ge, Hong-You; Arendt-Nielsen, Lars

    2011-10-01

    A latent myofascial trigger point (MTP) is defined as a focus of hyperirritability in a muscle taut band that is clinically associated with local twitch response and tenderness and/or referred pain upon manual examination. Current evidence suggests that the temporal profile of the spontaneous electrical activity at an MTP is similar to focal muscle fiber contraction and/or muscle cramp potentials, which contribute significantly to the induction of local tenderness and pain and motor dysfunctions. This review highlights the potential mechanisms underlying the sensory-motor dysfunctions associated with latent MTPs and discusses the contribution of central sensitization associated with latent MTPs and the MTP network to the spatial propagation of pain and motor dysfunctions. Treating latent MTPs in patients with musculoskeletal pain may not only decrease pain sensitivity and improve motor functions, but also prevent latent MTPs from transforming into active MTPs, and hence, prevent the development of myofascial pain syndrome.

  13. Synthesis and antibacterial studies of 2-aryl-3-alkanamido-4H-thiazolidin-4-one derivatives

    OpenAIRE

    Sandeep Jain; Ashwani Kumar; Mahesh Kumar; Neelam Jain

    2016-01-01

    A series of 2-aryl-3-alkanamido-4H-thiazolidin-4-ones were synthesized from long chain fatty acid hydrazides and studied for their in vitro antibacterial activity. Long chain fatty acid hydrazides 1 on reaction with different aromatic aldehydes in the presence of catalytic amount of glacial acetic acid yielded the corresponding aryl hydrazones 2 which on further reaction with thioglycolic acid in the presence of anhydrous zinc chloride furnished the title compounds 3. These compounds were cha...

  14. An air-stable copper reagent for nucleophilic trifluoromethylthiolation of aryl halides

    KAUST Repository

    Weng, Zhiqiang

    2012-12-12

    A series of copper(I) trifluoromethyl thiolate complexes have been synthesized from the reaction of CuF2 with Me3SiCF 3 and S8 (see scheme; Cu red, F green, N blue, S yellow). These air-stable complexes serve as reagents for the efficient conversion of a wide range of aryl halides into the corresponding aryl trifluoromethyl thioethers in excellent yields. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Photoinduced C-C Cross-Coupling of Aryl Chlorides and Inert Arenes

    Directory of Open Access Journals (Sweden)

    Lele Wang

    2016-01-01

    Full Text Available Here we report a facile, efficient, and catalyst-free method to realize C-C cross-coupling of aryl chlorides and inert arenes under UV light irradiation. The aryl radical upon homolytic cleavage of C-Cl bond initiated the nucleophilic substitution reaction with inert arenes to give biaryl products. This mild reaction mode can also be applied to other synthetic reactions, such as the construction of C-N bonds and trifluoromethylated compounds.

  16. Copper-Promoted Desulfitative N-Arylation of Sulfonamides and Sulfoximines with Sodium Arylsulfinates.

    Science.gov (United States)

    Jiang, Yangji; You, Yaping; Dong, Wanrong; Peng, Zhihong; Zhang, Yingjun; An, Delie

    2017-06-02

    A general and direct N-arylation of sulfonamides and NH-sulfoximines by sodium arylsulfinates through a desulfitative pathway was herein demonstrated. The reaction proceeded with catalytic loadings of Cu(II)-catalysts without any external ligands. And the novel arylation protocol featured for high efficiency (up to 93% yields) and good substituent tolerance (up to 53 examples). Moreover, a plausible reaction mechanism was also discussed.

  17. A mild procedure for α,α-dichlorination of cyclic aryl ketones using commercial bleach

    International Nuclear Information System (INIS)

    Quintiliano, Samir A.P.; Silva Junior, Luiz F.

    2007-01-01

    α,α-Dichloro-cyclic aryl ketones were obtained treating a methanolic solution of the corresponding ketone with commercial bleach at ambient conditions in yields varying from 61 to 92%. Electron-donating and -withdrawing groups in the starting ketone are tolerated but the reaction appears to be sensitive to steric effects. Moreover, five-, six-, and seven-membered aryl-cycloalkanones can be used as substrate. (author)

  18. Syntheses of 1-Aryl-5-nitro-1H-indazoles and a General One-Pot Route to 1-Aryl-1H-indazoles

    Directory of Open Access Journals (Sweden)

    Joel K. Annor-Gyamfi

    2018-03-01

    Full Text Available An efficient route to substituted 1-aryl-1H-indazoles has been developed and optimized. The method involved the preparation of arylhydrazones from acetophenone or benzaldehyde substituted by fluorine at C2 and nitro at C5, followed by deprotonation and nucleophilic aromatic substitution (SNAr ring closure in 45–90%. Modification of this procedure to a one-pot domino process was successful in the acetophenone series (73–96%, while the benzaldehyde series (63–73% required a step-wise addition of reagents. A general one-pot protocol for 1-aryl-1H-indazole formation without the limiting substitution patterns required for the SNAr cyclization has also been achieved in 62–78% yields. A selection of 1-aryl-1H-indazoles was prepared in high yield by a procedure that requires only a single laboratory operation.

  19. ATLAS trigger: Design and commissioning

    Science.gov (United States)

    Pastore, F.; Atlas Collaboration

    2012-12-01

    The ATLAS detector at CERN's Large Hadron Collider (LHC) will be exposed to proton-proton collisions from beams crossing at 40 MHz. A three-level trigger system was designed to select potentially interesting events and reduce the incoming rate to 100-200 Hz. The first trigger level (LVL1) is implemented in custom-built electronics, the second and third trigger levels are realised in software. The trigger system and its design parameters will be described with focus on computing and data aquision challenges. The results from both commissioning cosmic runs and first experiences from the LHC beam in 2008 will be overviewed. These running periods allowed us to exercise the trigger system online, including its configuration and monitoring infrastructure, as well as reconstruction and selection algorithms. The details on the plans for commissioning the ATLAS trigger when the LHC starts operations will be presented.

  20. The synthesis of α-aryl-α-aminophosphonates and α-aryl-α-aminophosphine oxides by the microwave-assisted Pudovik reaction

    Directory of Open Access Journals (Sweden)

    Erika Bálint

    2017-01-01

    Full Text Available A family of α-aryl-α-aminophosphonates and α-aryl-α-aminophosphine oxides was synthesized by the microwave-assisted solvent-free addition of dialkyl phosphites and diphenylphosphine oxide, respectively, to imines formed from benzaldehyde derivatives and primary amines. After optimization, the reactivity was mapped, and the fine mechanism was evaluated by DFT calculations. Two α-aminophosphonates were subjected to an X-ray study revealing a racemic dimer formation made through a N–H···O=P intermolecular hydrogen bridges pair.

  1. Aryl nucleoside H-phosphonates. Part 15: Synthesis, properties and, anti-HIV activity of aryl nucleoside 5'-alpha-hydroxyphosphonates.

    Science.gov (United States)

    Szymańska, Agnieszka; Szymczak, Marzena; Boryski, Jerzy; Stawiński, Jacek; Kraszewski, Adam; Collu, Gabriella; Sanna, Giseppina; Giliberti, Gabriele; Loddo, Roberta; La Colla, Paolo

    2006-03-15

    Aryl nucleoside 5'-H-phosphonates 4 bearing AZT or 2',3'-dideoxyuridine moieties were subjected to reaction with various aromatic aldehydes to produce nucleoside 5'-alpha-hydroxyphosphonate derivatives 2 as potential anti-HIV agents. Stability of the title compounds in cell culture media was investigated and three distinct decomposition pathways were identified. The anti-HIV activity of hydroxyphosphonates 2 correlates well with the type and extent of their chemical or enzymatic degradation in culture medium (RPMI 1640 containing 10% FBS), suggesting that aryl nucleoside 5'-hydroxyphosphonates 2 act as depot forms of the parent antiviral nucleosides.

  2. Rhodium-catalyzed asymmetric arylation of cyclic N-sulfonyl aryl alkyl ketimines: efficient access to highly enantioenriched α-tertiary amines.

    Science.gov (United States)

    Jiang, Tao; Wang, Zheng; Xu, Ming-Hua

    2015-02-06

    A simple catalyst system of Rh(I)/sulfur-olefin with exceptional catalytic performance has been developed for the highly enantioselective arylation of cyclic N-sulfonyl aryl alkyl ketimines with arylboroxines/arylboronic acids. Optically active α-arylalkyl-substituted benzosultams and benzosulfamidates which are generally difficult to obtain were easily prepared with excellent stereocontrol (up to 99.9% ee). The synthetic utility of the approach was demonstrated by the facile construction of NMDA antagonist FR115427 and benzoxazinone derivatives. This protocol offers new opportunities for the efficient synthesis of diverse chiral α-tertiary amines.

  3. Treating hydrocarbon oils

    Energy Technology Data Exchange (ETDEWEB)

    Scott, R.; MacIvor, W.

    1869-09-01

    The treatment of hydrocarbon oils, such as coal or shale oils, paraffin oils, and petroleum, either in the crude or more or less refined state has the object of reducing the specific gravity and otherwise improving the qualities of such oils. The oil to be treated is put into any ordinary still and distilled. The vapor escaping during the distillation is passed through one or more heating vessels or chambers and exposed to the heat necessary to produce the change. The heating vessels or chambers may be made of metal, clay, or any other material adapted to endure heat, and they may be made of any desired form, or they may be constituted of a coil of metal pipes or a series of tubes such as are used for heating air for blast furnaces.

  4. Flexible trigger menu implementation on the Global Trigger for the CMS Level-1 trigger upgrade

    Science.gov (United States)

    MATSUSHITA, Takashi; CMS Collaboration

    2017-10-01

    The CMS experiment at the Large Hadron Collider (LHC) has continued to explore physics at the high-energy frontier in 2016. The integrated luminosity delivered by the LHC in 2016 was 41 fb‑1 with a peak luminosity of 1.5 × 1034 cm‑2s‑1 and peak mean pile-up of about 50, all exceeding the initial estimations for 2016. The CMS experiment has upgraded its hardware-based Level-1 trigger system to maintain its performance for new physics searches and precision measurements at high luminosities. The Global Trigger is the final step of the CMS Level-1 trigger and implements a trigger menu, a set of selection requirements applied to the final list of objects from calorimeter and muon triggers, for reducing the 40 MHz collision rate to 100 kHz. The Global Trigger has been upgraded with state-of-the-art FPGA processors on Advanced Mezzanine Cards with optical links running at 10 GHz in a MicroTCA crate. The powerful processing resources of the upgraded system enable implementation of more algorithms at a time than previously possible, allowing CMS to be more flexible in how it handles the available trigger bandwidth. Algorithms for a trigger menu, including topological requirements on multi-objects, can be realised in the Global Trigger using the newly developed trigger menu specification grammar. Analysis-like trigger algorithms can be represented in an intuitive manner and the algorithms are translated to corresponding VHDL code blocks to build a firmware. The grammar can be extended in future as the needs arise. The experience of implementing trigger menus on the upgraded Global Trigger system will be presented.

  5. Myofascial Trigger Point Pain Syndromes.

    Science.gov (United States)

    Gerwin, Robert D

    2016-10-01

    Myofascial pain syndromes caused by trigger points (TrPs) in muscle are a common cause of local and generalized pain. Trigger points are hyperirritable zones in contracted bands of muscle, thought to be caused by muscle overload or stress. Stress TrPs have characteristic electromyographic features, and can be visualized with ultrasound and magnetic resonance elastography. Trigger point needling or injection can be effective in inactivating TrP, but correcting triggers is also critical. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  6. Cross-Coupling of Sodium Sulfinates with Aryl, Heteroaryl and Vinyl Halides by Nickel/photoredox dual catalysis

    KAUST Repository

    Yue, Huifeng

    2017-12-06

    An efficient photoredox/nickel dual catalyzed sulfonylation reaction of aryl, heteroaryl, and vinyl halides has been achieved for the first time. This newly developed sulfonylation protocol provides a versatile method for the synthesis of diverse aromatic sulfones at room temperature and shows excellent functional group tolerance. The electrophilic coupling partners are not limited to aryl, heteroaryl and vinyl bromides but also less reactive aryl chlorides are suitable substrates for this transformation.

  7. Microwave-assisted cyclizations promoted by polyphosphoric acid esters: a general method for 1-aryl-2-iminoazacycloalkanes

    Directory of Open Access Journals (Sweden)

    Jimena E. Díaz

    2016-09-01

    Full Text Available The first general procedure for the synthesis of 5 to 7-membered 1-aryl-2-iminoazacycloalkanes is presented, by microwave-assisted ring closure of ω-arylaminonitriles promoted by polyphosphoric acid (PPA esters. 1-Aryl-2-iminopyrrolidines were easily prepared from the acyclic precursors employing a chloroformic solution of ethyl polyphosphate (PPE. The use of trimethylsilyl polyphosphate (PPSE in solvent-free conditions allowed for the synthesis of 1-aryl-2-iminopiperidines and hitherto unreported 1-aryl-2-iminoazepanes. The cyclization reaction involves good to high yields and short reaction times, and represents a novel application of PPA esters in heterocyclic synthesis.

  8. New air-stable planar chiral ferrocenyl monophosphine ligands: Suzuki cross-coupling of aryl chlorides and bromides

    DEFF Research Database (Denmark)

    Jensen, Jakob Feldthusen; Johannsen, Mogens

    2003-01-01

    GraphicA novel class of planar chiral electron-rich monophosphine ligands has been developed. The modular design allows a short and efficient synthesis of an array of aryl-ferrocenyl derivatives carrying the donating bis(dicyclohexyl)phosphino moiety. These new ligands have successfully been appl...... applied in the palladium-catalyzed Suzuki cross-coupling of activated as well as nonactivated aryl chlorides at room temperature. The asymmetric coupling of an aryl bromide and an aryl boronic acid was also tested, giving ees up to 54%....

  9. Palladium-catalyzed aryl amination-heck cyclization cascade: A one-flask approach to 3-substituted Indoles

    DEFF Research Database (Denmark)

    Jensen, Thomas; Pedersen, Henrik; Bang-Andersen, B.

    2008-01-01

    Two for the price of one: A Pd/dppf-based catalyst provides access to the title compounds from 1,2-dihalogenated aromatic compounds and allylic amines in a single reaction flask. The initial aryl amination step occurs with excellent selectivity for the aryl iodide to ensure the formation of a sin......Two for the price of one: A Pd/dppf-based catalyst provides access to the title compounds from 1,2-dihalogenated aromatic compounds and allylic amines in a single reaction flask. The initial aryl amination step occurs with excellent selectivity for the aryl iodide to ensure the formation...

  10. Thermally activated trigger device

    International Nuclear Information System (INIS)

    Harty, R.B.; Camaret, T.L.

    1988-01-01

    This patent describes a nuclear space reactor, a thermally activated trigger device for rendering the reactor subcritical upon reentry to the earth's atmosphere, the device comprising: a closed vessel, a piston slideably mounted in the vessel to divide it into first and second compartments, an inert gas contained within each of the compartments at substantially the same pressure, a connecting rod operatively connected to the piston and to actuator means, the actuator means providing for moving means for rendering the reactor subcritical upon movement of the connecting rod; a bellows having opposite ends, one of the ends being affixed to and in sealing engagement with the connecting rod and the other of the ends being affixed to and in sealing engagement with the vessel for permitting linear movement of the connecting rod and preventing any escape of the inert gas from the closed vessel; and normally closed pipes communicating with one of the compartments for venting the inert gas therefrom when any of the pipes is open, the pipes being located at different parts of the nuclear space reactor so that the closed ends thereof are exposed to the atmosphere upon reentry of the reactor to the atmosphere. The pipes are designed to open at a selected temperature resulting from the reentry so that the gas leaves the communicating compartment via an open pipe to cause a difference in pressure between the compartments sufficient for the higher pressure in the other compartment to move the piston and thereby activate the actuator means

  11. Trigger and data acquisition

    CERN Multimedia

    CERN. Geneva; Gaspar, C

    2001-01-01

    Past LEP experiments generate data at 0.5 MByte/s from particle detectors with over a quarter of a million readout channels. The process of reading out the electronic channels, treating them, and storing the date produced by each collision for further analysis by the physicists is called "Data Acquisition". Not all beam crossings produce interesting physics "events", picking the interesting ones is the task of the "Trigger" system. In order to make sure that the data is collected in good conditions the experiment's operation has to be constantly verified. In all, at LEP experiments over 100 000 parameters were monitored, controlled, and synchronized by the "Monotoring and control" system. In the future, LHC experiments will produce as much data in a single day as a LEP detector did in a full year's running with a raw data rate of 10 - 100 MBytes/s and will have to cope with some 800 million proton-proton collisions a second of these collisions only one in 100 million million is interesting for new particle se...

  12. Oxidative stress in entomopathogenic fungi grown on insect-like hydrocarbons.

    Science.gov (United States)

    Huarte-Bonnet, Carla; Juárez, M Patricia; Pedrini, Nicolás

    2015-08-01

    Entomopathogenic fungi mostly attack their insect hosts by penetration through the cuticle. The outermost insect surface is covered by a lipid-rich layer, usually composed of very long chain hydrocarbons. These fungi are apt to grow on straight chain hydrocarbons (alkanes) as the sole carbon source. Insect-like hydrocarbons are first hydroxylated by a microsomal P450 monooxygenase system, and then fully catabolized by peroxisomal β-oxidation reactions in Beauveria bassiana. In this review, we will discuss lipid metabolism adaptations in alkane-grown fungi, and how an oxidative stress scenario is established under these conditions. Fungi have to pay a high cost for hydrocarbon utilization; high levels of reactive oxygen species are produced and a concomitant antioxidant response is triggered in fungal cells to cope with this drawback.

  13. Environmental Ligands of the Aryl Hydrocarbon Receptor and Their Effects in Models of Adult Liver Progenitor Cells

    Czech Academy of Sciences Publication Activity Database

    Vondráček, Jan; Machala, M.

    2016-01-01

    Roč. 2016, Č.2016 (2016), č. článku 4326194. E-ISSN 1687-9678 R&D Projects: GA ČR GA13-07711S Institutional support: RVO:68081707 Keywords : growth-factor-alpha * stem-like cells * junctional intercellular communication Subject RIV: BO - Biophysics

  14. Estrogen-, androgen- and aryl hydrocarbon receptor mediated activities in passive and composite samples from municipal waste and surface waters.

    Science.gov (United States)

    Jálová, V; Jarošová, B; Bláha, L; Giesy, J P; Ocelka, T; Grabic, R; Jurčíková, J; Vrana, B; Hilscherová, K

    2013-09-01

    Passive and composite sampling in combination with in vitro bioassays and identification and quantification of individual chemicals were applied to characterize pollution by compounds with several specific modes of action in urban area in the basin of two rivers, with 400,000 inhabitants and a variety of industrial activities. Two types of passive samplers, semipermeable membrane devices (SPMD) for hydrophobic contaminants and polar organic chemical integrative samplers (POCIS) for polar compounds such as pesticides and pharmaceuticals, were used to sample wastewater treatment plant (WWTP) influent and effluent as well as rivers upstream and downstream of the urban complex and the WWTP. Compounds with endocrine disruptive potency were detected in river water and WWTP influent and effluent. Year-round, monthly assessment of waste waters by bioassays documented estrogenic, androgenic and dioxin-like potency as well as cytotoxicity in influent waters of the WWTP and allowed characterization of seasonal variability of these biological potentials in waste waters. The WWTP effectively removed cytotoxic compounds, xenoestrogens and xenoandrogens. There was significant variability in treatment efficiency of dioxin-like potency. The study indicates that the WWTP, despite its up-to-date technology, can contribute endocrine disrupting compounds to the river. Riverine samples exhibited dioxin-like, antiestrogenic and antiandrogenic potencies. The study design enabled characterization of effects of the urban complex and the WWTP on the river. Concentrations of PAHs and contaminants and specific biological potencies sampled by POCIS decreased as a function of distance from the city. © 2013.

  15. Role of aryl hydrocarbon receptor in modulation of the expression of the hypoxia marker carbonic anhydrase IX

    Czech Academy of Sciences Publication Activity Database

    Takáčová, M.; Holotňáková, T.; Vondráček, Jan; Machala, M.; Pěnčíková, K.; Gradin, K.; Poellinger, L.; Pastorek, J.; Pastoreková, S.; Kopáček, J.

    2009-01-01

    Roč. 419, - (2009), s. 419-425 ISSN 0264-6021 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : AhR * carbonic anhydrase IX * dioxin Subject RIV: BO - Biophysics Impact factor: 5.155, year: 2009

  16. Gene expression changes in human prostate carcinoma cells exposed to genotoxic and nongenotoxic aryl hydrocarbon receptor ligands

    Czech Academy of Sciences Publication Activity Database

    Hrubá, E.; Vondráček, Jan; Líbalová, Helena; Topinka, Jan; Bryja, Vítězslav; Souček, Karel; Machala, M.

    2011-01-01

    Roč. 206, č. 2 (2011), s. 178-188 ISSN 0378-4274 R&D Projects: GA ČR(CZ) GA310/07/0961; GA ČR(CZ) GA524/09/1337 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702; CEZ:AV0Z50390512; CEZ:AV0Z50390703 Keywords : LNCaP cell s * AhR ligands * WNT5A Subject RIV: BO - Biophysics Impact factor: 3.230, year: 2011

  17. The aryl hydrocarbon receptor suppresses osteoblast proliferation and differentiation through the activation of the ERK signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Haitao; Du, Yuxuan; Zhang, Xulong; Sun, Ying; Li, Shentao; Dou, Yunpeng [Department of Immunology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men, Beijing 100069 (China); Li, Zhanguo [Department of Rheumatology and Immunology, Clinical Immunology Center, Peking University People' s Hospital, No. 11 Xizhimen South Street, Beijing 100044 (China); Yuan, Huihui, E-mail: huihui_yuan@163.com [Department of Immunology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men, Beijing 100069 (China); Zhao, Wenming, E-mail: zhao-wenming@163.com [Department of Immunology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men, Beijing 100069 (China)

    2014-11-01

    Ahr activation is known to be associated with synovitis and exacerbated rheumatoid arthritis (RA), but its contributions to bone loss have not been completely elucidated. Osteoblast proliferation and differentiation are abnormal at the erosion site in RA. Here, we reported that the expression of Ahr was increased in the hind paws' bone upon collagen-induced arthritis (CIA) in mice, and the levels of Ahr were negatively correlated with bone mineral density (BMD). In addition, immunofluorescent staining showed that the high expression of Ahr was mainly localized in osteoblasts from the CIA mice compared to normal controls. Moreover, the luciferase intensity of Ahr in the nucleus increased by 12.5% in CIA osteoblasts compared to that in normal controls. In addition, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) activation of the Ahr inhibited pre-osteoblast MC3T3-E1 cellular proliferation and differentiation in a dose-dependent manner. Interestingly, the levels of alkaline phosphatase (ALP) mRNA expression in the osteoblasts of CIA mice were reduced compared to normal controls. In contrast, decreased ALP expression by activated Ahr was completely reversed after pretreatment with an Ahr inhibitor (CH-223191) in MC3T3-E1 cell lines and primary osteoblasts on day 5. Our data further showed that activation of Ahr promoted the phosphorylation of ERK after 5 days. Moreover, Ahr-dependent activation of the ERK signaling pathway decreased the levels of proliferation cells and inhibited ALP activity in MC3T3-E1 cells. These results demonstrated that the high expression of Ahr may suppress osteoblast proliferation and differentiation through activation of the ERK signaling pathway, further enabling bone erosion in CIA mice. - Highlights: • The upregulation of Ahr was localized in osteoblasts of CIA mice. • The overexpression of Ahr suppressed osteoblast development. • The Ahr activated ERK signaling pathway to exacerbate bone erosion.

  18. Genetic basis for evolved tolerance to dioxin-like pollutants in wild Atlantic killifish: more than the aryl hydrocarbon receptor

    Science.gov (United States)

    Atlantic killifish (Fundulus heteroclitus) resident to some US urban and industrialized estuaries demonstrate recently evolved and extreme tolerance to toxic dioxin-like compounds (DLCs). Here we provide an unusually comprehensive accounting (69%) through Quantitative Trait Locu...

  19. Tin-oxo clusters based on aryl arsonate anions.

    Science.gov (United States)

    Xie, Yun-Peng; Yang, Jin; Ma, Jian-Fang; Zhang, Lai-Ping; Song, Shu-Yan; Su, Zhong-Min

    2008-01-01

    Reactions of Ph(3)SnOH or Ph3SnCl with aryl arsonic acids RAsO3H2, where R=C6H5 (1), 2-NH2C6H4 (2), 4-NH2C6H4 (3), 2-NO2C6H4 (4), 3-NO2C6H4 (5), 4-NO2C6H4 (6), 3-NO2-4-OHC6H3 (7), 2-ClC6H4 (8) and 2,4-Cl2C6H3 (9), gave 18 Sn-O cluster compounds. These compounds can be classified into four types: type A: [{(PhSn)3(RAsO3)3(mu3-O)(OH)(R'O)2}2Sn] (R=C6H5, 2-NH2C6H4, 4-NH2C6H4, 2-NO2C6H4, 3-NO2C6H4, 2-ClC6H4, 2,4-Cl2C6H3, and 3-NO2-4-OHC6H3; R'=Me or Et); type B: [{(PhSn)3(RAsO3)(2)(RAsO3H)(mu3-O)(R'O)2}2] (R=4-NO2C6H4, R'=Me); type C: [{(PhSn)3(RAsO3)3(mu3-O)(R'O)3}2Sn] (R=2,4-Cl2C6H3, R'=Me); type D: [{Sn3Cl3(mu3-O)(R'O)3}(2)(RAsO3)4] (R=2-NO2C6H4 and 4-NO2-C6H4; R'=Me or Et). Structures of types A and B contain [Sn3(mu3-O)(mu2-OR')2] building blocks, while in types C and D the stannoxane cores are built from two [Sn3(mu3-O)(mu2-OR')3] building blocks. The reactions proceeded with partial or complete dearylation of the triphenyltin precursor. These various structural forms are realized by subtle changes in the nature of the organotin precursors and aryl arsonic acids. The syntheses, structures, and structural interrelationship of these organostannoxanes are discussed.

  20. The role of aryl hydrocarbon receptor in regulation of enzymes involved in metabolic activation of polycyclic aromatic hydrocarbons in a model of rat liver progenitor cells

    Czech Academy of Sciences Publication Activity Database

    Vondráček, Jan; Krčmář, P.; Procházková, Jiřina; Trilecová, L.; Gavelová, M.; Skálová, L.; Szotáková, B.; Bunček, M.; Radilová, H.; Kozubík, Alois; Machala, M.

    2009-01-01

    Roč. 180, č. 2 (2009), s. 226-237 ISSN 0009-2797 R&D Projects: GA ČR(CZ) GA524/06/0517 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : cytochromes P450 * PAHs * aldo-keto reductases Subject RIV: BO - Biophysics Impact factor: 2.457, year: 2009

  1. Assessment of the aryl hydrocarbon receptor-mediated activities of polycyclic aromatic hydrocarbons in a human cell-based reporter gene assay

    Czech Academy of Sciences Publication Activity Database

    Vondráček, Jan; Pěnčíková, K.; Neca, J.; Ciganek, M.; Grycová, A.; Dvořák, Z.; Machala, M.

    2017-01-01

    Roč. 220, JAN2017 (2017), s. 307-316 ISSN 0269-7491 R&D Projects: GA ČR GA13-07711S Institutional support: RVO:68081707 Keywords : rat primary hepatocytes * liver epithelial-cells * cancer-risk assessment Subject RIV: BO - Biophysics Impact factor: 5.099, year: 2016

  2. The TOTEM modular trigger system

    Energy Technology Data Exchange (ETDEWEB)

    Bagliesi, M.G., E-mail: mg.bagliesi@pi.infn.i [University of Siena and INFN Pisa (Italy); Berretti, M.; Cecchi, R.; Greco, V.; Lami, S.; Latino, G.; Oliveri, E.; Pedreschi, E.; Scribano, A.; Spinella, F.; Turini, N. [University of Siena and INFN Pisa (Italy)

    2010-05-21

    The TOTEM experiment will measure the total cross-section with the luminosity independent method and study elastic and diffractive scattering at the LHC. We are developing a modular trigger system, based on programmable logic, that will select meaningful events within 2.5{mu}s. The trigger algorithm is based on a tree structure in order to obtain information compression. The trigger primitive is generated directly on the readout chip, VFAT, that has a specific fast output that gives low resolution hits information. In two of the TOTEM detectors, Roman Pots and T2, a coincidence chip will perform track recognition directly on the detector readout boards, while for T1 the hits are transferred from the VFATs to the trigger hardware. Starting from more than 2000 bits delivered by the detector electronics, we extract, in a first step, six trigger patterns of 32 LVDS signals each; we build, then, on a dedicated board, a 1-bit (L1) trigger signal for the TOTEM experiment and 16 trigger bits to the CMS experiment global trigger system for future common data taking.

  3. The TOTEM modular trigger system

    International Nuclear Information System (INIS)

    Bagliesi, M.G.; Berretti, M.; Cecchi, R.; Greco, V.; Lami, S.; Latino, G.; Oliveri, E.; Pedreschi, E.; Scribano, A.; Spinella, F.; Turini, N.

    2010-01-01

    The TOTEM experiment will measure the total cross-section with the luminosity independent method and study elastic and diffractive scattering at the LHC. We are developing a modular trigger system, based on programmable logic, that will select meaningful events within 2.5μs. The trigger algorithm is based on a tree structure in order to obtain information compression. The trigger primitive is generated directly on the readout chip, VFAT, that has a specific fast output that gives low resolution hits information. In two of the TOTEM detectors, Roman Pots and T2, a coincidence chip will perform track recognition directly on the detector readout boards, while for T1 the hits are transferred from the VFATs to the trigger hardware. Starting from more than 2000 bits delivered by the detector electronics, we extract, in a first step, six trigger patterns of 32 LVDS signals each; we build, then, on a dedicated board, a 1-bit (L1) trigger signal for the TOTEM experiment and 16 trigger bits to the CMS experiment global trigger system for future common data taking.

  4. Upgrade trigger: Biannual performance update

    CERN Document Server

    Aaij, Roel; Couturier, Ben; Esen, Sevda; De Cian, Michel; De Vries, Jacco Andreas; Dziurda, Agnieszka; Fitzpatrick, Conor; Fontana, Marianna; Grillo, Lucia; Hasse, Christoph; Jones, Christopher Rob; Le Gac, Renaud; Matev, Rosen; Neufeld, Niko; Nikodem, Thomas; Polci, Francesco; Del Buono, Luigi; Quagliani, Renato; Schwemmer, Rainer; Seyfert, Paul; Stahl, Sascha; Szumlak, Tomasz; Vesterinen, Mika Anton; Wanczyk, Joanna; Williams, Mark Richard James; Yin, Hang; Zacharjasz, Emilia Anna

    2017-01-01

    This document presents the performance of the LHCb Upgrade trigger reconstruction sequence, incorporating changes to the underlying reconstruction algorithms and detector description since the Trigger and Online Upgrade TDR. An updated extrapolation is presented using the most recent example of an Event Filter Farm node.

  5. Growth of hydrocarbon utilizing microorganisms

    Digital Repository Service at National Institute of Oceanography (India)

    Bhosle, N.B.; Mavinkurve, S.

    Two isolates from marine mud having broad spectrum hydrocarbon utilizing profile were identified as Arthrobacter simplex and Candida tropicalis.Both the organisms grew exponentially on crude oil. The cell yield of the organisms was influenced...

  6. Predicting hydrocarbon release from soil

    International Nuclear Information System (INIS)

    Poppendieck, D.; Loehr, R.C.

    2002-01-01

    'Full text:' The remediation of hazardous chemicals from soils can be a lengthy and costly process. As a result, recent regulatory initiatives have focused on risk-based corrective action (RBCA) approaches. Such approaches attempt to identify the amount of chemical that can be left at a site with contaminated soil and still be protective of human health and the environment. For hydrocarbons in soils to pose risk to human heath and the environment, the hydrocarbons must be released from the soil and accessible to microorganisms, earthworms, or other higher level organisms. The sorption of hydrocarbons to soil can reduce the availability of the hydrocarbon to receptors. Typically in soils and sediments, there is an initial fast release of a hydrocarbon from the soil to the aqueous phase followed by a slower release of the remaining hydrocarbon to the aqueous phase. The rate and extent of slow release can influence aqueous hydrocarbon concentrations and the fate and transport of hydrocarbons in the subsurface. Once the fast fraction of the chemical has been removed from the soil, the remaining fraction of a chemical may desorb at a rate that natural mechanisms can attenuate the released hydrocarbon. Hence, active remediation may be needed only until the fast fraction has been removed. However, the fast fraction is a soil and chemical specific parameter. This presentation will present a tier I type protocol that has been developed to quickly estimate the fraction of hydrocarbons that are readily released from the soil matrix to the aqueous phase. Previous research in our laboratory and elsewhere has used long-term desorption (four months) studies to determine the readily released fraction. This research shows that a single short-term (less than two weeks) batch extraction procedure provides a good estimate of the fast released fraction derived from long-term experiments. This procedure can be used as a tool to rapidly evaluate the release and bioavailability of

  7. LIQUID HYDROCARBON FUEL CELL DEVELOPMENT.

    Science.gov (United States)

    A compound anode consists of a reforming catalyst bed in direct contact with a palladium-silver fuel cell anode. The objective of this study was to...prove the feasibility of operating a compound anode fuel cell on a liquid hydrocarbon and to define the important parameters that influence cell...performance. Both reformer and fuel cell tests were conducted with various liquid hydrocarbon fuels. Included in this report is a description of the

  8. Hydrocarbon removal with constructed wetlands

    OpenAIRE

    Eke, Paul Emeka

    2008-01-01

    Wetlands have long played a significant role as natural purification systems, and have been effectively used to treat domestic, agricultural and industrial wastewater. However, very little is known about the biochemical processes involved, and the use of constructed treatment wetlands in the removal of petroleum aromatic hydrocarbons from produced and/or processed water. Wastewaters from the oil industry contain aromatic hydrocarbons such as benzene, toluene, ethylbenzene and x...

  9. Bioassay of polycyclic aromatic hydrocarbons

    Energy Technology Data Exchange (ETDEWEB)

    Van Kirk, E.A.

    1980-08-01

    A positive relationship was found between the photodynamic activity of 24 polycyclic aromatic hydrocarbons versus published results on the mutagenicity, carcinogenicity, and initiation of unscheduled DNA synthesis. Metabolic activation of benzo(a)pyrene resulted in detection of increased mutagenesis in Paramecium tetraurelia as found also in the Ames Salmonella assay. The utility of P. tetraurelia as a biological detector of hazardous polycyclic aromatic hydrocarbons is discussed.

  10. HYDROCARBONS RESERVES IN VENEZUELA

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez Cruz, D.J.

    2007-07-01

    Venezuela is an important player in the energy world, because of its hydrocarbons reserves. The process for calculating oil and associated gas reserves is described bearing in mind that 90% of the gas reserves of Venezuela are associated to oil. Likewise, an analysis is made of the oil reserves figures from 1975 to 2003. Reference is also made to inconsistencies found by international experts and the explanations offered in this respect by the Ministry of Energy and Petroleum (MENPET) and Petroleos de Venezuela (PDVSA) regarding the changes that took place in the 1980s. In turn, Hubbert's Law is explained to determine peak production of conventional oil that a reservoir or field will reach, as well as its relationship with remaining reserves. Emphasis is placed on the interest of the United Nations on this topic. The reserves of associated gas are presented along with their relationship with the different crude oils that are produced and with injected gas, as well as with respect to the possible changes that would take place in the latter if oil reserves are revised. Some recommendations are submitted so that the MENPET starts preparing the pertinent policies ruling reserves. (auth)

  11. Decorating poly(alkyl aryl-ether) dendrimers with metallacarboranes.

    Science.gov (United States)

    Núñez, Rosario; Juárez-Pérez, Emilio José; Teixidor, Francesc; Santillan, Rosa; Farfán, Norberto; Abreu, Arturo; Yépez, Rebeca; Viñas, Clara

    2010-11-01

    A new family of polyanionic poly(alkyl aryl-ether) metallodendrimers decorated with four and eight cobaltabisdicarbollide units have been obtained in high yield by the ring-opening reaction of cyclic oxonium [3,3'-Co(8-(C(2)H(4)O)(2)-1,2-C(2)B(9)H(10))(1',2'-C(2)B(9)H(11))] with alkoxides formed by deprotonation of terminal alcohols in the α,α'-bis[3,5-bis(hydroxymehyl)phenoxy]-p-xylene, α,α'-bis[3,5-bis(hydroxymehyl)phenoxy]-m-xylene, α,α'-bis[3,5-bis-[3,5-bis(hydroxymethyl)phenoxy]methylen]phenoxy]-p-xylene, and α,α,'-bis[3,5-bis-[3,5-bis(hydroxymethyl)phenoxy]methylen]phenoxy]-m-xylene dendrimers. The crystal structure of the precursor α,α'-bis[3,5-bis(chloromethyl)phenoxy]-p-xylene is also described. Final products are fully characterized by FTIR, NMR, UV-vis spectroscopies and elemental analysis. For metallodendrimers, the UV-vis absorptions have been a good tool for estimating the experimental number of cobaltabisdicarbollide units peripherally attached to the dendrimeric structure and consequently to corroborate the complete functionalization of the dendrimers.

  12. DUMAND data acquisition with triggering

    International Nuclear Information System (INIS)

    Brenner, A.E.; Theriot, D.; March, R.H.

    1980-01-01

    A data acquisition scheme for the standard DUMAND array that includes a simple triggering scheme as a fundamental part of the system is presented. Although there are a number of not yet fully understood parameters, it is assumed that thresholds can be set in such a manner as to give rise to a triggered signal that is not so dominated by randoms that it gives a substantial decrease in the data acquisition rate over that which would be required by a nontriggered system. It is also assumed that the triggering logic is relatively simple and does not need major computational capabilities for a trigger logic decision. With these assumptions, it is possible to generate the trigger at the array and restrict the data transfer to shore. However, with a not unreasonable delay of 200 microseconds, it is even possible to transmit the information for the trigger to shore and perform all that logic on the shore. The critical point is to send the minimum amount of information necessary to construct the trigger such that one need not send all the possible information in all detectors of the array continuously to shore. 1 figure

  13. ATLAS Trigger: design and commissioning

    CERN Document Server

    Pastore, F; The ATLAS collaboration

    2009-01-01

    The ATLAS detector at CERN's Large Hadron Collider (LHC) will be exposed to proton-proton collisions from beams crossing at 40 MHz. A three-level trigger system was designed to select potentially interesting events and reduce the incoming rate to 100-200 Hz. The first trigger level (LVL1) is implemented in custom-built electronics, the second and third trigger levels are realised in software. Based on calorimeter information and hits in dedicated muon-trigger detectors, the LVL1 decision is made by the central-trigger processor yielding an output rate of less than 100 kHz. The allowed latency for the trigger decision at this stage is less than 2.5 micro seconds. The two subsequent levels, called, High-Level Trigger (HLT) further reduce the rate to the offline storage rate while retaining the most interesting physics. The HLT is implemented in software running in commercially available computer farms and consists of Level 2 and Event Filter. To reduce the network data traffic and the processing time to managea...

  14. The ATLAS Missing ET trigger

    CERN Document Server

    Beauchemin, P; The ATLAS collaboration

    2010-01-01

    Over the last few months, the ATLAS detector collected 900 GeV LHC collision events which allowed for the study the performance of the ATLAS Trigger and Data Acquisition system (TDAQ). With the 7 TeV collision data collected recently, the performance studies of the trigger system are critical for a successful physics program. In particular a large spectrum of physics results will rely on the capacity of the ATLAS TDAQ system to collect events based on the estimate of the missing transverse energy (MET) contained in each event. The MET trigger would be, for example, the primary trigger to be used in new physics searches for processes involving new weakly interacting particles, which could account for the astronomically observed dark matter. In addition to discovery perspectives, the MET trigger can also be used in combination with other triggers to control the rate of signatures involving low energy objects. For example, the MET trigger is necessary in order to measure non-boosted W in the tau channel. Finally...

  15. Enhanced interfacial properties of carbon fiber composites via aryl diazonium reaction “on water”

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yuwei [School of Chemical Engineering and Technology, Harbin Institute of Technology, Harbin 150001 (China); College of Materials Science and Engineering, Qiqihar University, Qiqihar 161006 (China); Meng, Linghui [School of Chemical Engineering and Technology, Harbin Institute of Technology, Harbin 150001 (China); Fan, Liquan [School of Chemical Engineering and Technology, Harbin Institute of Technology, Harbin 150001 (China); College of Materials Science and Engineering, Qiqihar University, Qiqihar 161006 (China); Ma, Lichun; Qi, Meiwei; Yu, Jiali [School of Chemical Engineering and Technology, Harbin Institute of Technology, Harbin 150001 (China); Huang, Yudong, E-mail: ydhuang.hit1@yahoo.com.cn [School of Chemical Engineering and Technology, Harbin Institute of Technology, Harbin 150001 (China)

    2014-10-15

    Highlights: • Carbon fibers are grafted with phenyl amine group via aryl diazonium reaction. • Interfacial shear strength of the carbon fibers increases by 73%. • Tensile strength of the carbon fibers does not decrease distinctly. • Using water as the reaction medium can avoid pollution from organic solvents. • Grafting via aryl diazonium reaction in one step can improve modification efficiency. - Abstract: Polyacrylonitrile-based carbon fibers were functionalized with phenyl amine group via aryl diazonium reaction “on water” to improve their interfacial bonding with resin matrix. Raman spectroscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and scanning electron microscopy were employed to characterize ordered degree, functional groups, chemical states and morphology of carbon fiber surface, respectively. The results showed that phenyl amine groups were grafted on the fiber surface successfully. Mechanical property test results indicated that the aryl diazonium reaction in this paper could improve the interfacial shear strength by 73%, while the tensile strength was down very slightly. Hence aryl diazonium reaction “on water” could be a facile green platform to functionalize carbon fibers for many interesting applications.

  16. Mechanistic Aspects of Aryl-Halide Oxidative Addition, Coordination Chemistry, and Ring-Walking by Palladium.

    Science.gov (United States)

    Zenkina, Olena V; Gidron, Ori; Shimon, Linda J W; Iron, Mark A; van der Boom, Milko E

    2015-11-02

    This contribution describes the reactivity of a zero-valent palladium phosphine complex with substrates that contain both an aryl halide moiety and an unsaturated carbon-carbon bond. Although η(2) -coordination of the metal center to a C=C or C≡C unit is kinetically favored, aryl halide bond activation is favored thermodynamically. These quantitative transformations proceed under mild reaction conditions in solution or in the solid state. Kinetic measurements indicate that formation of η(2) -coordination complexes are not nonproductive side-equilibria, but observable (and in several cases even isolated) intermediates en route to aryl halide bond cleavage. At the same time, DFT calculations show that the reaction with palladium may proceed through a dissociation-oxidative addition mechanism rather than through a haptotropic intramolecular process (i.e., ring walking). Furthermore, the transition state involves coordination of a third phosphine to the palladium center, which is lost during the oxidative addition as the C-halide bond is being broken. Interestingly, selective activation of aryl halides has been demonstrated by adding reactive aryl halides to the η(2) -coordination complexes. The product distribution can be controlled by the concentration of the reactants and/or the presence of excess phosphine. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Expedient synthesis of C-aryl carbohydrates by consecutive biocatalytic benzoin and aldol reactions.

    Science.gov (United States)

    Hernández, Karel; Parella, Teodor; Joglar, Jesús; Bujons, Jordi; Pohl, Martina; Clapés, Pere

    2015-02-16

    The introduction of aromatic residues connected by a C-C bond into the non-reducing end of carbohydrates is highly significant for the development of innovative structures with improved binding affinity and selectivity (e.g., C-aril-sLex). In this work, an expedient asymmetric "de novo" synthetic route to new aryl carbohydrate derivatives based on two sequential stereoselectively biocatalytic carboligation reactions is presented. First, the benzoin reaction of aromatic aldehydes to dimethoxyacetaldehyde is conducted, catalyzed by benzaldehyde lyase from Pseudomonas fluorescens biovar I. Then, the α-hydroxyketones formed are reduced by using NaBH4 yielding the anti diol. After acetal hydrolysis, the aldol addition of dihydroxyacetone, hydroxyacetone, or glycolaldehyde catalyzed by the stereocomplementary D-fructose-6-phosphate aldolase and L-rhamnulose-1-phosphate aldolase is performed. Both aldolases accept unphosphorylated donor substrates, avoiding the need of handling the phosphate group that the dihydroxyacetone phosphate-dependent aldolases require. In this way, 6-C-aryl-L-sorbose, 6-C-aryl-L-fructose, 6-C-aryl-L-tagatose, and 5-C-aryl-L-xylose derivatives are prepared by using this methodology. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Enhanced interfacial properties of carbon fiber composites via aryl diazonium reaction “on water”

    International Nuclear Information System (INIS)

    Wang, Yuwei; Meng, Linghui; Fan, Liquan; Ma, Lichun; Qi, Meiwei; Yu, Jiali; Huang, Yudong

    2014-01-01

    Highlights: • Carbon fibers are grafted with phenyl amine group via aryl diazonium reaction. • Interfacial shear strength of the carbon fibers increases by 73%. • Tensile strength of the carbon fibers does not decrease distinctly. • Using water as the reaction medium can avoid pollution from organic solvents. • Grafting via aryl diazonium reaction in one step can improve modification efficiency. - Abstract: Polyacrylonitrile-based carbon fibers were functionalized with phenyl amine group via aryl diazonium reaction “on water” to improve their interfacial bonding with resin matrix. Raman spectroscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and scanning electron microscopy were employed to characterize ordered degree, functional groups, chemical states and morphology of carbon fiber surface, respectively. The results showed that phenyl amine groups were grafted on the fiber surface successfully. Mechanical property test results indicated that the aryl diazonium reaction in this paper could improve the interfacial shear strength by 73%, while the tensile strength was down very slightly. Hence aryl diazonium reaction “on water” could be a facile green platform to functionalize carbon fibers for many interesting applications

  19. Triggered Release from Polymer Capsules

    Energy Technology Data Exchange (ETDEWEB)

    Esser-Kahn, Aaron P. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Chemistry; Odom, Susan A. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Chemistry; Sottos, Nancy R. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Materials Science and Engineering; White, Scott R. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Aerospace Engineering; Moore, Jeffrey S. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Chemistry

    2011-07-06

    Stimuli-responsive capsules are of interest in drug delivery, fragrance release, food preservation, and self-healing materials. Many methods are used to trigger the release of encapsulated contents. Here we highlight mechanisms for the controlled release of encapsulated cargo that utilize chemical reactions occurring in solid polymeric shell walls. Triggering mechanisms responsible for covalent bond cleavage that result in the release of capsule contents include chemical, biological, light, thermal, magnetic, and electrical stimuli. We present methods for encapsulation and release, triggering methods, and mechanisms and conclude with our opinions on interesting obstacles for chemically induced activation with relevance for controlled release.

  20. Seismology: dynamic triggering of earthquakes.

    Science.gov (United States)

    Gomberg, Joan; Johnson, Paul

    2005-10-06

    After an earthquake, numerous smaller shocks are triggered over distances comparable to the dimensions of the mainshock fault rupture, although they are rare at larger distances. Here we analyse the scaling of dynamic deformations (the stresses and strains associated with seismic waves) with distance from, and magnitude of, their triggering earthquake, and show that they can cause further earthquakes at any distance if their amplitude exceeds several microstrain, regardless of their frequency content. These triggering requirements are remarkably similar to those measured in the laboratory for inducing dynamic elastic nonlinear behaviour, which suggests that the underlying physics is similar.

  1. ATLAS FTK: Fast Track Trigger

    CERN Document Server

    Amerio, S; The ATLAS collaboration; Andreazza, A; Annovi, A; Beretta, M; Bevacqua, V; Bogdan, M; Bossini, E; Boveia, A; Cavaliere, V; Canelli, F; Blazey, G; Cervigni, F; Cheng, Y; Citterio, M; Crescioli, F; Dell’Orso, M; Drake, G; Dunford, M; Giannetti, P; Giorgi, F; Hoff, J; Kapliy, A; Kasten, M; Kim, Y K; Kimura, N; Lanza, A; Liberali, V; Liu, T; Magalotti, D; McCarn, A; Melachrinos, C; Meroni, C; Negri, A; Neubauer, M; Penning, B; Piendibene, M; Proudfoot, J; Riva, M; Roda, C; Sabatini, F; Sacco, I; Shochet, M; Stabile, A; Tang, F; Tang, J; Tripiccione, R; Tuggle, J; Vercesi, V; Verzocchi, M; Villa, M; Vitillo, R A; Volpi, G; Webster, J; Wu, J; Yorita, K; Zhang, J

    2011-01-01

    A track reconstruction system for the trigger of the ATLAS detector at the Large Hadron Collider is described. The Fast Tracker is a highly parallel hardware system designed to operate at the Level-1 trigger output rate. It will provide high-quality tracks reconstructed over the entire inner detector by the start of processing in the Level-2 trigger. The system is based on associative memories for pattern recognition and fast FPGA’s for track reconstruction. Its design and expected performance under instantaneous luminosities up to 3 × 10^34/cm^2/s are discussed.

  2. Synthesis of radiolabelled aryl azides from diazonium salts: experimental and computational results permit the identification of the preferred mechanism.

    Science.gov (United States)

    Joshi, Sameer M; de Cózar, Abel; Gómez-Vallejo, Vanessa; Koziorowski, Jacek; Llop, Jordi; Cossío, Fernando P

    2015-05-28

    Experimental and computational studies on the formation of aryl azides from the corresponding diazonium salts support a stepwise mechanism via acyclic zwitterionic intermediates. The low energy barriers associated with both transition structures are compatible with very fast and efficient processes, thus making this method suitable for the chemical synthesis of radiolabelled aryl azides.

  3. Homocoupling of aryl halides in flow: Space integration of lithiation and FeCl3 promoted homocoupling

    Directory of Open Access Journals (Sweden)

    Aiichiro Nagaki

    2011-08-01

    Full Text Available The use of FeCl3 resulted in a fast homocoupling of aryllithiums, and this enabled its integration with the halogen–lithium exchange reaction of aryl halides in a flow microreactor. This system allows the homocoupling of two aryl halides bearing electrophilic functional groups, such as CN and NO2, in under a minute.

  4. Copper-Catalyzed N-Arylation of Amides Using (S-N-Methylpyrrolidine-2-carboxylate as the Ligand

    Directory of Open Access Journals (Sweden)

    Dong-Sheng Ma

    2010-03-01

    Full Text Available (S-N-methylpyrrolidine-2-carboxylate, a derivative of natural L-proline, was found to be an efficient ligand for the copper-catalyzed Goldberg-type N-arylation of amides with aryl halides under mild conditions. A variety of N-arylamides were synthesized in good to high yields.

  5. The HLT inclusive B triggers

    CERN Document Server

    Gligorov, Vladimir V; Williams, Michael

    2011-01-01

    The inclusive HLT strategy relies on triggering any B decay based on two signatures: a single significantly displaced, high transverse momentum track, and a significantly displaced vertex containing this track and 1-3 other tracks, with high total transverse momentum. In order to provide optimal signal efficiency and background rejection the displaced vertex selection is implemented in a novel boosted decision tree algorithm incorporating information about the experimental resolution in the boosting procedure to protect against overtraining. The performance of these triggers has been commissioned using data taken during 2011 LHCb running and is evaluated here in a data-driven manner. The HLT inclusive triggers are found to have a rejection factor of around 1000 with respect to events selected by the L0 hardware trigger and a bbar purity close to 100%.

  6. GnRH agonist triggering

    DEFF Research Database (Denmark)

    Kol, Shahar; Humaidan, Peter; Al Humaidan, Peter Samir Heskjær

    2013-01-01

    The concept that a bolus of gonadotrophin-releasing hormone agonist (GnRHa) can replace human chorionic gonadotrophin (HCG) as a trigger of final oocyte maturation was introduced several years ago. Recent developments in the area strengthen this premise. GnRHa trigger offers important advantages......, including virtually complete prevention of ovarian hyperstimulation syndrome (OHSS), the introduction of a surge of FSH in addition to the LH surge and finally the possibility to individualize luteal-phase supplementation based on ovarian response to stimulation. We maintain that the automatic HCG...... triggering concept should be challenged and that the GnRHa trigger is the way to move forward with thoughtful consideration of the needs, safety and comfort of our patients. Routinely, human chorionic gonadotrophin (HCG) is used to induce ovulation in fertility treatments. This approach deviates...

  7. FERMIGTRIG - Fermi GBM Trigger Catalog

    Data.gov (United States)

    National Aeronautics and Space Administration — This table lists all of the triggers observed by one or more of the 14 GBM detectors (12 NaI and 2 BGO). Note that there are two Browse catalogs resulting from GBM...

  8. The CDF level-3 trigger

    International Nuclear Information System (INIS)

    Devlin, T.

    1993-01-01

    The Collider Detector at Fermilab (CDF) has been operating at the Tevatron and collecting data on proton-antiproton interactions with collision rates above 250,000 Hz. Three levels of filtering select events for data logging at a rate of about 4 Hz. The Level 3 trigger provides most of the capabilities of the offline production programs for event reconstruction and physics analysis. The type of physics triggers, application of cuts, and combinations of logical requirements for event selection are controlled at run time by a trigger table using a syntax fully integrated with the Level 1 and Level 2 hardware triggers. The level 3 software operates in 48 RISC/UNIX processors (over 1000 mips) served by four 20-MByte/sec data buses for input, output and control. The system architecture, debugging, code validation, error reporting, analysis capabilities and performance will be described

  9. Enhanced interfacial properties of carbon fiber composites via aryl diazonium reaction “on water”

    Science.gov (United States)

    Wang, Yuwei; Meng, Linghui; Fan, Liquan; Ma, Lichun; Qi, Meiwei; Yu, Jiali; Huang, Yudong

    2014-10-01

    Polyacrylonitrile-based carbon fibers were functionalized with phenyl amine group via aryl diazonium reaction "on water" to improve their interfacial bonding with resin matrix. Raman spectroscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and scanning electron microscopy were employed to characterize ordered degree, functional groups, chemical states and morphology of carbon fiber surface, respectively. The results showed that phenyl amine groups were grafted on the fiber surface successfully. Mechanical property test results indicated that the aryl diazonium reaction in this paper could improve the interfacial shear strength by 73%, while the tensile strength was down very slightly. Hence aryl diazonium reaction "on water" could be a facile green platform to functionalize carbon fibers for many interesting applications.

  10. N-aryl pyrrolo-tetrathiafulvalene based ligands: synthesis and metal coordination.

    Science.gov (United States)

    Balandier, Jean-Yves; Chas, Marcos; Dron, Paul I; Goeb, Sébastien; Canevet, David; Belyasmine, Ahmed; Allain, Magali; Sallé, Marc

    2010-03-05

    A straightforward general synthetic access to N-aryl-1,3-dithiolo[4,5-c]pyrrole-2-thione derivatives 6 from acetylenedicarbaldehyde monoacetal is depicted. In addition to their potentiality as precursors to dithioalkyl-pyrrole derivatives, thiones 6 are key building blocks to N-aryl monopyrrolo-tetrathiafulvalene (MPTTF) derivatives 10. X-ray structures of four of these thiones intermediates, reminiscent of the corresponding MPTTF derivatives, are provided. When the aryl group is a binding pyridyl unit, the MPTTF derivative 10a can coordinate M(II) salts (M = Pt, Pd). The first examples of metal-directed orthogonal MPTTF-based dimers 11-14, obtained through coordination of 10a to cis-blocked square planar Pt or Pd complexes are described. Studies on the parameters influencing the dimer construction are presented, as well as first recognition properties of the resulting electron-rich clip for C(60).

  11. Palladium-catalyzed aryl C-H olefination with unactivated, aliphatic alkenes.

    Science.gov (United States)

    Deb, Arghya; Bag, Sukdev; Kancherla, Rajesh; Maiti, Debabrata

    2014-10-01

    Palladium-catalyzed coupling between aryl halides and alkenes (Mizoroki-Heck reaction) is one of the most popular reactions for synthesizing complex organic molecules. The limited availability, problematic synthesis, and higher cost of aryl halide precursors (or their equivalents) have encouraged exploration of direct olefination of aryl carbon-hydrogen (C-H) bonds (Fujiwara-Moritani reaction). Despite significant progress, the restricted substrate scope, in particular noncompliance of unactivated aliphatic olefins, has discouraged the use of this greener alternative. Overcoming this serious limitation, we report here a palladium-catalyzed chelation-assisted ortho C-H bond olefination of phenylacetic acid derivatives with unactivated, aliphatic alkenes in good to excellent yields with high regio- and stereoselectivities. The versatility of this operationally simple method has been demonstrated through drug diversification and sequential C-H olefination for synthesizing divinylbenzene derivatives.

  12. Aryl Polyenes, a Highly Abundant Class of Bacterial Natural Products, Are Functionally Related to Antioxidative Carotenoids.

    Science.gov (United States)

    Schöner, Tim A; Gassel, Sören; Osawa, Ayako; Tobias, Nicholas J; Okuno, Yukari; Sakakibara, Yui; Shindo, Kazutoshi; Sandmann, Gerhard; Bode, Helge B

    2016-02-02

    Bacterial pigments of the aryl polyene type are structurally similar to the well-known carotenoids with respect to their polyene systems. Their biosynthetic gene cluster is widespread in taxonomically distant bacteria, and four classes of such pigments have been found. Here we report the structure elucidation of the aryl polyene/dialkylresorcinol hybrid pigments of Variovorax paradoxus B4 by HPLC-UV-MS, MALDI-MS and NMR. Furthermore, we show for the first time that this pigment class protects the bacterium from reactive oxygen species, similarly to what is known for carotenoids. An analysis of the distribution of biosynthetic genes for aryl polyenes and carotenoids in bacterial genomes is presented; it shows a complementary distribution of these protective pigments in bacteria. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Organometallic myoglobins: Formation of Fe-carbon bonds and distal pocket effects on aryl ligand conformations.

    Science.gov (United States)

    Wang, Bing; Thomas, Leonard M; Richter-Addo, George B

    2016-11-01

    Bioorganometallic Fe-C bonds are biologically relevant species that may result from the metabolism of natural or synthetic hydrazines. The molecular structures of four new sperm whale mutant myoglobin derivatives with Fe-aryl moieties, namely H64A-tolyl-m, H64A-chlorophenyl-p, H64Q-tolyl-m, and H64Q-chlorophenyl-p, have been determined at 1.7-1.9Å resolution. The structures reveal conformational preferences for the substituted aryls resulting from attachment of the aryl ligands to Fe at the site of net -NHNH 2 release from the precursor hydrazines, and show distal pocket changes that readily accommodate these bulky ligands. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. B physics triggers at CMS

    CERN Document Server

    Starodumov, Andrei

    2003-01-01

    The CMS detector is mainly designed to investigate hard events. Only few Level-1 Trigger conditions are suitable to select soft B-meson decays. The B-physics potential of CMS depends strongly on a selection strategy at High-Level Trigger. The selection algorithms for some benchmark B-decay channels that allow CMS to perform competitive B-physics program are presented.

  15. Hydrocarbons at the toe of the Nankai Accretionary Prism- Evidence from 3d Seismic Reflection

    Science.gov (United States)

    Heffernan, A. S.

    2002-12-01

    The toe of the Nankai accretionary prism is a dynamic hydrogeologic environment that has been intensively studied in recent years. Fluid flow plays a critical role in the prism's structural development, and strongly influences fault behavior in an example of the tectonic setting that is responsible for generating the world's largest earthquakes. Thermogenic and biogenic hydrocarbon generation and migration are part of this larger fluid flow system, and are of particular interest because hydrocarbons are the components of flow that are mostly likely to be imaged with existing geophysical tools. 3d seismic reflection data collected in 1999 contain indicators of this active hydrocarbon system, including evidence for a structurally trapped hydrocarbon accumulation, as well as possible sea-floor hydrocarbon seepage. A high amplitude, positive polarity, horizontal reflector can be observed cross-cutting folded reflectors within the hangingwall anticline above the frontal thrust. This flat spot occurs in an area with 4-way structural closure, and is interpreted as representing a gas-water contact and as a direct geophysical indicator of a shallow hydrocarbon accumulation. It is approximately 3 km southwest of ODP site 808, where log and core data confirm the presence of both thermogenic and biogenic hydrocarbons. A prominent headscarp exists on the seafloor directly above this flat spot, indicating that slope failure has occurred. As seafloor seepage is known to affect slope stability, it is possible that seepage from the shallow hydrocarbon reservoir plays a role in triggering slope failure in overlying sediments. This gas accumulation represents the first known structurally trapped hydrocarbon reservoir at the frontal fold of an accretionary prism. It indicates high fluid pressure that apparently affects surficial processes. Finally it indicates that 3D seismic data is needed to properly locate interesting geologic/hydrologic drilling targets and study them in a

  16. Syntrophic biodegradation of hydrocarbon contaminants.

    Science.gov (United States)

    Gieg, Lisa M; Fowler, S Jane; Berdugo-Clavijo, Carolina

    2014-06-01

    Anaerobic environments are crucial to global carbon cycling wherein the microbial metabolism of organic matter occurs under a variety of redox conditions. In many anaerobic ecosystems, syntrophy plays a key role wherein microbial species must cooperate, essentially as a single catalytic unit, to metabolize substrates in a mutually beneficial manner. Hydrocarbon-contaminated environments such as groundwater aquifers are typically anaerobic, and often methanogenic. Syntrophic processes are needed to biodegrade hydrocarbons to methane, and recent studies suggest that syntrophic hydrocarbon metabolism can also occur in the presence of electron acceptors. The elucidation of key features of syntrophic processes in defined co-cultures has benefited greatly from advances in 'omics' based tools. Such tools, along with approaches like stable isotope probing, are now being used to monitor carbon flow within an increasing number of hydrocarbon-degrading consortia to pinpoint the key microbial players involved in the degradative pathways. The metagenomic sequencing of hydrocarbon-utilizing consortia should help to further identify key syntrophic features and define microbial interactions in these complex communities. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. N,N-Diethylurea-Catalyzed Amidation between Electron-Defficient Aryl Azides and Phenylacetaldehydes

    Science.gov (United States)

    Xie, Sheng; Ramström, Olof; Yan, Mingdi

    2015-01-01

    Urea structures, of which N,N-diethylurea (DEU) proved to be the most efficient, were discovered to catalyze amidation reactions between electron-defficient aryl azides and phenylacetaldehydes. Experimental data support 1,3-dipolar cycloaddition between DEU-activated enols and electrophilic phenyl azides, especially perfluoroaryl azides, followed by rearrangement of the triazoline intermediate. The activation of the aldehyde under near-neutral conditions was of special importance in inhibiting dehydration/aromatization of the triazoline intermediate, thus promoting the rearrangement to form aryl amides. PMID:25616121

  18. N,N-diethylurea-catalyzed amidation between electron-deficient aryl azides and phenylacetaldehydes.

    Science.gov (United States)

    Xie, Sheng; Ramström, Olof; Yan, Mingdi

    2015-02-06

    Urea structures, of which N,N-diethylurea (DEU) proved to be the most efficient, were discovered to catalyze amidation reactions between electron-deficient aryl azides and phenylacetaldehydes. Experimental data support 1,3-dipolar cycloaddition between DEU-activated enols and electrophilic phenyl azides, especially perfluoroaryl azides, followed by rearrangement of the triazoline intermediate. The activation of the aldehyde under near-neutral conditions was of special importance in inhibiting dehydration/aromatization of the triazoline intermediate, thus promoting the rearrangement to form aryl amides.

  19. Asymmetric synthesis of quaternary aryl amino acid derivatives via a three-component aryne coupling reaction

    Directory of Open Access Journals (Sweden)

    Elizabeth P. Jones

    2011-11-01

    Full Text Available A method was developed for the synthesis of α-alkyl, α-aryl-bislactim ethers in good to excellent yields and high diastereoselectivities, consisting of a facile one-pot procedure in which the aryl group is introduced by means of a nucleophilic addition to benzyne and the alkyl group by alkylation of a resultant benzylic anion. Hydrolysis of the sterically less hindered adducts gave the corresponding quaternary amino acids with no racemization, whereas hydrolytic ring opening gave the corresponding valine dipeptides from bulkier bislactims.

  20. Podophyllum hexandrum Offers Radioprotection by Modulating Free Radical Flux: Role of Aryl-Tetralin Lignans

    OpenAIRE

    Chawla, Raman; Arora, Rajesh; Singh, Shikha; Sagar, R. K.; Sharma, Rakesh Kumar; Kumar, R.; Sharma, A.; Tripathi, R. P.; Puri, C.; Khan, H. A.; Shawl, A. S.; Sultan, P.; Krishan, Tej; Qazi, G. N.

    2006-01-01

    We have evaluated the effect of variation in aryl-tetralin lignans on the radioprotective properties of Podophyllum hexandrum. Two fractionated fractions of P. hexandrum [methanolic (S1) and chloroform fractions (S2)], with varying aryl-tetralin lignan content were utilized for the present study. The peroxyl ion scavenging potentials of S1 and S2 were found to be comparable [i.e. 45.88% (S1) and 41% (S2)] after a 48 h interval in a time-dependent study, whereas in a 2 h study, S2 exhibite...

  1. Catalytic Asymmetric Ring-Opening Reactions of Aziridines with 3-Aryl-Oxindoles.

    Science.gov (United States)

    Wang, Linqing; Li, Dan; Yang, Dongxu; Wang, Kezhou; Wang, Jie; Wang, Pengxin; Su, Wu; Wang, Rui

    2016-03-04

    A highly enantioselective ring-opening alkylation reaction between 3-aryl-oxindole and N-(2-picolinoyl) aziridine has been realized for the first time. The reaction is efficiently mediated by a simple in-situ-generated magnesium catalyst and 3,3'-fluorinated-BINOL (BINOL=1,1'-binaphthalene-2,2'-diol) has been identified as a powerful chiral ligand. Notably, the fluorine atom on the chiral ligand plays a key role in providing the desired chiral 3-alkyl-3-aryl oxindoles with excellent enantioselectivities. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Modular approach to novel chiral aryl-ferrocenyl phosphines by Suzuki cross-coupling

    DEFF Research Database (Denmark)

    Jensen, Jakob Feldthusen; Søtofte, Inger; Sorensen, H.O.

    2002-01-01

    Two novel planar chiral and atropisomeric P,N and P,O aryl-ferrocenyl ligand systems have been developed. The strategy is short and involves a new synthetic approach to aryl-ferrocenyl compounds via a Suzuki cross-coupling procedure. The modular design can easily give access to variety of chiral ...... mono- and bidentate ligands. Two simple derivatives of a novel chiral bidenate P,N ligand belonging to the MOPF family have been synthesized and tested in the enantioselective copper-catalyzed addition of diethyl zinc to an enone and a "difficult" diester. Moderate to excellent yields...

  3. Flexible trigger menu implementation on the Global Trigger for the CMS Level-1 trigger upgrade

    CERN Document Server

    Matsushita, Takashi

    2017-01-01

    The CMS experiment at the Large Hadron Collider (LHC) has continued to explore physics at the high-energy frontier in 2016. The integrated luminosity delivered by the LHC in 2016 was 41~fb$^{-1}$ with a peak luminosity of 1.5 $\\times$ 10$^{34}$ cm$^{-2}$s$^{-1}$ and peak mean pile-up of about 50, all exceeding the initial estimations for 2016. The CMS experiment has upgraded its hardware-based Level-1 trigger system to maintain its performance for new physics searches and precision measurements at high luminosities. The Global Trigger is the final step of the CMS \\mbox{Level-1} trigger and implements a trigger menu, a set of selection requirements applied to the final list of objects from calorimeter and muon triggers, for reducing the 40 MHz collision rate to 100 kHz. The Global Trigger has been upgraded with state-of-the-art FPGA processors on Advanced Mezzanine Cards with optical links running at 10 GHz in a MicroTCA crate. The powerful processing resources of the upgraded system enable implemen...

  4. A new face of phenalenyl-based radicals in the transition metal-free C-H arylation of heteroarenes at room temperature: trapping the radical initiatorviaC-C σ-bond formation.

    Science.gov (United States)

    Ahmed, Jasimuddin; P, Sreejyothi; Vijaykumar, Gonela; Jose, Anex; Raj, Manthan; Mandal, Swadhin K

    2017-11-01

    The radical-mediated transition metal-free approach for the direct C-H bond functionalization of arenes is considered as a cost effective alternative to transition metal-based catalysis. An organic ligand-based radical plays a key role by generating an aryl radical which undergoes a subsequent functionalization process. The design principle of the present study takes advantage of a relatively stable odd alternant hydrocarbon-based phenalenyl (PLY) radical. In this study, the first transition metal-free catalyzed direct C-H arylation of a variety of heteroarenes such as azoles, furan, thiophene and pyridine at room temperature has been reported using a phenalenyl-based radical without employing any photoactivation step. This protocol has been successfully applied to the gram scale synthesis of core moieties of bioactive molecules. The phenalenyl-based radical initiator has been characterized crystallographically by trapping it via the formation of a C-C σ-bond between the phenalenyl radical and solvent-based radical species.

  5. Synthesis of 3-(3-aryl-pyrrolidin-1-yl)-5-aryl-1,2,4-triazines that have antibacterial activity and also inhibit inorganic pyrophosphatase.

    Science.gov (United States)

    Lv, Wei; Banerjee, Biplab; Molland, Katrina L; Seleem, Mohamed N; Ghafoor, Adil; Hamed, Maha I; Wan, Baojie; Franzblau, Scott G; Mesecar, Andrew D; Cushman, Mark

    2014-01-01

    Inorganic pyrophosphatases are potential targets for the development of novel antibacterial agents. A pyrophosphatase-coupled high-throughput screening assay intended to detect o-succinyl benzoic acid coenzyme A (OSB CoA) synthetase inhibitors led to the unexpected discovery of a new series of novel inorganic pyrophosphatase inhibitors. Lead optimization studies resulted in a series of 3-(3-aryl-pyrrolidin-1-yl)-5-aryl-1,2,4-triazine derivatives that were prepared by an efficient synthetic pathway. One of the tetracyclic triazine analogues 22h displayed promising antibiotic activity against a wide variety of drug-resistant Staphylococcus aureus strains, as well as activity versus Mycobacterium tuberculosis and Bacillus anthracis, at a concentration that was not cytotoxic to mammalian cells. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. External triggering and triggered targeting strategies for drug delivery

    Science.gov (United States)

    Wang, Yanfei; Kohane, Daniel S.

    2017-06-01

    Drug delivery systems that are externally triggered to release drugs and/or target tissues hold considerable promise for improving the treatment of many diseases by minimizing nonspecific toxicity and enhancing the efficacy of therapy. These drug delivery systems are constructed from materials that are sensitive to a wide range of external stimuli, including light, ultrasound, electrical and magnetic fields, and specific molecules. The responsiveness conferred by these materials allows the release of therapeutics to be triggered on demand and remotely by a physician or patient. In this Review, we describe the rationales for such systems and the types of stimuli that can be deployed, and provide an outlook for the field.

  7. Trigger processing using reconfigurable logic in the CMS calorimeter trigger

    CERN Document Server

    Brooke, J J; Heath, G P; Maddox, A J; Newbold, D; Rabbetts, P D

    2001-01-01

    We present the design of the Global Calorimeter Trigger processor for the CMS detector at LHC. This is a fully pipelined processor system which collects data from all the CMS calorimeters and produces summary information used in forming the Level-1 trigger decision for each event. The design in based on the use of state-of-the-art reconfigurable logic devices (FPGAs) and fast data links. We present the results of device testing using a low-latency pipelined sort algorithm, which demonstrate that an FPGA can be used to perform processing previously foreseen to require custom ASICs. Our design approach results in a powerful, flexible and compact processor system. (0 refs).

  8. Review Document: Full Software Trigger

    CERN Document Server

    Albrecht, J; Raven, G

    2014-01-01

    This document presents a trigger system for the upgraded LHCb detector, scheduled to begin operation in 2020. This document serves as input for the internal review towards the "DAQ, online and trigger TDR". The proposed trigger system is implemented entirely in software. In this document we show that track reconstruction of a similar quality to that available in the offline algorithms can be performed on the full inelastic $pp$-collision rate, without prior event selections implemented in custom hardware and without relying upon a partial event reconstruction. A track nding eciency of 98.8 % relative to oine can be achieved for tracks with $p_T >$ 500 MeV/$c$. The CPU time required for this reconstruction is about 40 % of the available budget. Proof-of-principle selections are presented which demonstrate that excellent performance is achievable using an inclusive beauty trigger, in addition to exclusive beauty and charm triggers. Finally, it is shown that exclusive beauty and charm selections that do not intr...

  9. Palladium- and copper-mediated N-aryl bond formation reactions for the synthesis of biological active compounds

    Directory of Open Access Journals (Sweden)

    Burkhard Koenig

    2011-01-01

    Full Text Available N-Arylated aliphatic and aromatic amines are important substituents in many biologically active compounds. In the last few years, transition-metal-mediated N-aryl bond formation has become a standard procedure for the introduction of amines into aromatic systems. While N-arylation of simple aromatic halides by simple amines works with many of the described methods in high yield, the reactions may require detailed optimization if applied to the synthesis of complex molecules with additional functional groups, such as natural products or drugs. We discuss and compare in this review the three main N-arylation methods in their application to the synthesis of biologically active compounds: Palladium-catalysed Buchwald–Hartwig-type reactions, copper-mediated Ullmann-type and Chan–Lam-type N-arylation reactions. The discussed examples show that palladium-catalysed reactions are favoured for large-scale applications and tolerate sterically demanding substituents on the coupling partners better than Chan–Lam reactions. Chan–Lam N-arylations are particularly mild and do not require additional ligands, which facilitates the work-up. However, reaction times can be very long. Ullmann- and Buchwald–Hartwig-type methods have been used in intramolecular reactions, giving access to complex ring structures. All three N-arylation methods have specific advantages and disadvantages that should be considered when selecting the reaction conditions for a desired C–N bond formation in the course of a total synthesis or drug synthesis.

  10. Effective viscosity of confined hydrocarbons

    DEFF Research Database (Denmark)

    Sivebæk, Ion Marius; Samoilov, V.N.; Persson, B.N.J.

    2012-01-01

    We present molecular dynamics friction calculations for confined hydrocarbon films with molecular lengths from 20 to 1400 carbon atoms. We find that the logarithm of the effective viscosity ηeff for nanometer-thin films depends linearly on the logarithm of the shear rate: log ηeff=C-nlog γ̇, where...

  11. Fast processor for dilepton triggers

    International Nuclear Information System (INIS)

    Katsanevas, S.; Kostarakis, P.; Baltrusaitis, R.

    1983-01-01

    We describe a fast trigger processor, developed for and used in Fermilab experiment E-537, for selecting high-mass dimuon events produced by negative pions and anti-protons. The processor finds candidate tracks by matching hit information received from drift chambers and scintillation counters, and determines their momenta. Invariant masses are calculated for all possible pairs of tracks and an event is accepted if any invariant mass is greater than some preselectable minimum mass. The whole process, accomplished within 5 to 10 microseconds, achieves up to a ten-fold reduction in trigger rate

  12. Upgrade trigger: Bandwidth strategy proposal

    CERN Document Server

    Fitzpatrick, Conor; Meloni, Simone; Boettcher, Thomas Julian; Whitehead, Mark Peter; Dziurda, Agnieszka; Vesterinen, Mika Anton

    2017-01-01

    This document describes a selection strategy for the upgrade trigger using charm signals as a benchmark. The Upgrade trigger uses a 'Run 2-like' sequence consisting of a first and second stage, in between which the calibration and alignment is performed. The first stage, HLT1, uses an inclusive strategy to select beauty and charm decays, while the second stage uses offline-quality exclusive selections. A novel genetic algorithm-based bandwidth division is performed at the second stage to distribute the output bandwidth among different physics channels, maximising the efficiency for useful physics events. The performance is then studied as a function of the available output bandwidth.

  13. Rosacea Triggers: Alcohol and Smoking.

    Science.gov (United States)

    Alinia, Hossein; Tuchayi, Sara Moradi; Patel, Nupur U; Patel, Nishit; Awosika, Olabola; Bahrami, Naeim; Cardwell, Leah A; Richardson, Irma; Huang, Karen E; Feldman, Steven R

    2018-04-01

    A variety of triggers are thought to exacerbate rosacea. A validated self-assessment tool and survey was used to study the relationship between rosacea severity and triggers. Subjects were adult patients with a clinical diagnosis of rosacea. Increased severity of disease was significantly associated with consumption of many alcoholic beverages in 1 day and employment at a job requiring extensive sun exposure. The authors' findings may inform physician counseling practices; patients may be provided with practical measures for managing their rosacea, such as limiting alcohol consumption over short periods of time and increasing sun protection, especially in the summer. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Ruthenium-Catalyzed γ-Carbolinium Ion Formation from Aryl Azides. Synthesis of Dimebolin

    Science.gov (United States)

    Dong, Huijun; Latka, Regina T.; Driver, Tom G.

    2011-01-01

    A range of γ-carbolines were produced stereoselectively from ruthenium(III)-catalyzed reactions of 3-pyridyl substituted aryl azides. Other catalysts and conditions were neither as selective nor as high yielding. This method was used to synthesize Dimebolin in a concise and efficient manner. PMID:21517088

  15. Ruthenium porphyrin catalyzed diimination of indoles with aryl azides as the nitrene source.

    Science.gov (United States)

    Wei, Jinhu; Xiao, Wenbo; Zhou, Cong-Ying; Che, Chi-Ming

    2014-03-28

    By using [Ru(TTP)CO] [H2TTP = meso-tetrakis(4-tolyl)porphyrin] as catalyst and aryl azides as the nitrene source, the sp(2)(C-H) bonds of a series of indoles undergo oxidative C-N bond formation to give unique 2,3-diimination products in good to high yields.

  16. Continuous flow photolysis of aryl azides: Preparation of 3H-azepinones

    Directory of Open Access Journals (Sweden)

    Farhan R. Bou-Hamdan

    2011-08-01

    Full Text Available Photolysis of aryl azides to give nitrenes, and their subsequent rearrangement in the presence of water to give 3H-azepinones, is performed in continuous flow in a photoreactor constructed of fluorinated ethylene polymer (FEP tubing. Fine tuning of the reaction conditions using the flow reactor allowed minimization of secondary photochemical reactions.

  17. Efficient and Simple Synthesis of 6-Aryl-1,4-dimethyl-9H-carbazoles

    Directory of Open Access Journals (Sweden)

    Sylvain Rault

    2008-06-01

    Full Text Available A synthetic method for the preparation of 6-aryl-1,4-dimethyl-9H-carbazoles involving a palladium catalyzed coupling reaction of 1,4-dimethyl-9H-carbazole-6-boronic acids and (heteroaryl halides is described.

  18. Amination of Aryl Halides and Esters Using Intensified Continuous Flow Processing.

    Science.gov (United States)

    Kohl, Thomas M; Hornung, Christian H; Tsanaktsidis, John

    2015-09-25

    Significant process intensification of the amination reactions of aryl halides and esters has been demonstrated using continuous flow processing. Using this technology traditionally difficult amination reactions have been performed safely at elevated temperatures. These reactions were successfully conducted on laboratory scale coil reactor modules with 1 mm internal diameter (ID) and on a preparatory scale tubular reactor with 6 mm ID containing static mixers.

  19. Enantioselective Decarboxylative Arylation of α-Amino Acids via the Merger of Photoredox and Nickel Catalysis

    Science.gov (United States)

    Zuo, Zhiwei; Cong, Huan; Li, Wei; Choi, Junwon; Fu, Gregory C.; MacMillan, David W. C.

    2016-01-01

    An asymmetric decarboxylative Csp3–Csp2 cross-coupling has been achieved via the synergistic merger of photoredox and nickel catalysis. This mild, operationally simple protocol transforms a wide variety of naturally abundant α-amino acids and readily available aryl halides into valuable chiral benzylic amines in high enantiomeric excess, thereby producing motifs found in pharmacologically active agents. PMID:26849354

  20. Enantioselective α-Arylation of Carbonyls via Cu(I)-Bisoxazoline Catalysis

    Science.gov (United States)

    Harvey, James S.; Simonovich, Scott P.; Jamison, Christopher R.; MacMillan, David W. C.

    2011-01-01

    The enantioselective α-arylation of both lactones and acyl oxazolidones has been accomplished using a combination of diaryliodonium salts and copper catalysis. These mild catalytic conditions provide a new strategy for the enantioselective construction and retention of enolizable α-carbonyl benzylic stereocenters, a valuable synthon for the production of medicinal agents. PMID:21848265

  1. Pd-catalysed ligand-enabled carboxylate-directed highly regioselective arylation of aliphatic acids

    Science.gov (United States)

    Zhu, Yan; Chen, Xiaolan; Yuan, Chunchen; Li, Guobao; Zhang, Jingyu; Zhao, Yingsheng

    2017-04-01

    α-amino acids bearing aromatic side chains are important synthetic units in the synthesis of peptides and natural products. Although various β-C-H arylation methodologies for amino acid derivatives involving the assistance of directing groups have been extensively developed, syntheses that directly employ N-protected amino acids as starting materials remain rare. Herein, we report an N-acetylglycine-enabled Pd-catalysed carboxylate-directed β-C(sp3)-H arylation of aliphatic acids. In this way, various non-natural amino acids can be directly prepared from phthaloylalanine in one step in good to excellent yields. Furthermore, a series of aliphatic acids have been shown to be amenable to this transformation, affording β-arylated propionic acid derivatives in moderate to good yields. More importantly, this ligand-enabled direct β-C(sp3)-H arylation could be easily scaled-up to 10 g under reflux conditions, highlighting the potential utility of this synthetic method.

  2. Three New Sesquiterpene Aryl Esters from the Mycelium of Armillaria mellea.

    Science.gov (United States)

    Chen, Chien-Chih; Kuo, Yueh-Hsiung; Cheng, Jing-Jy; Sung, Ping-Jyun; Ni, Ching-Li; Chen, Chin-Chu; Shen, Chien-Chang

    2015-05-29

    Three new sesquiterpene aryl esters and eight known compounds were isolated from the EtOH extract of the mycelium of Armillaria mellea. The structures of new compounds were established by analysis of their spectroscopic data. Some of the isolates showed cytotoxicity to a variety of cancer cell lines, including MCF-7, H460, HT-29, and CEM.

  3. Three New Sesquiterpene Aryl Esters from the Mycelium of Armillaria mellea

    Directory of Open Access Journals (Sweden)

    Chien-Chih Chen

    2015-05-01

    Full Text Available Three new sesquiterpene aryl esters and eight known compounds were isolated from the EtOH extract of the mycelium of Armillaria mellea. The structures of new compounds were established by analysis of their spectroscopic data. Some of the isolates showed cytotoxicity to a variety of cancer cell lines, including MCF-7, H460, HT-29, and CEM.

  4. Nickel-Catalyzed Synthesis of Primary Aryl and Heteroaryl Amines via C–O Bond Cleavage

    KAUST Repository

    Yue, Huifeng

    2017-03-13

    A nickel-catalyzed protocol for the conversion of aryl and heteroaryl alcohol derivatives to primary and secondary aromatic amines via C(sp2)-O bond cleavage is described. The new amination protocol can be applied to a range of substrates bearing diverse functional groups and uses readily available benzophenone imines as an effective nitrogen source.

  5. Synthesis of 4-aryl-4, 5-dihydro-1-indeno [1, 2-] pyrimidines by ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Chemical Sciences; Volume 123; Issue 4. Synthesis of 4-aryl-4,5-dihydro-1-indeno[1,2-]pyrimidines by Biginelli condensation and their antibacterial activities. Ramandeep Kaur Monika Bansal Balbir Kaur Tulika Mishra Aruna Bhatia. Volume 123 Issue 4 July 2011 pp 443-451 ...

  6. Investigation of Keto-enol Tautomers during the Synthesis of Aryl-bis ...

    Indian Academy of Sciences (India)

    This study investigated the existence of keto-enol tautomers for the first time during the synthesis of aryl-bis(2-hydroxy-1-naphthyl)methane from 2-naphthol and -tolualdehyde or 4-chlorobenzaldehyde in methanol using CuSO4.5H2O as catalyst under reflux condition. The exclusive formation of ...

  7. A novel and facile approach for synthesis of 5-amino-7-aryl-6-cyano ...

    Indian Academy of Sciences (India)

    Vol. 124, No. 4, July 2012, pp. 893–899. c Indian Academy of Sciences. A novel and facile approach for synthesis of 5-amino-7-aryl-6-cyano-4H-pyrano[3,2-b] ... roles in biochemical process.9 Therefore, preparation of this heterocyclic nucleus has gained more importance in organic synthesis. The 4H-pyran derivatives are ...

  8. Structures and conformations of 1-aryl-1,4-dihydro-3(2 H)-isoquinolinones

    Science.gov (United States)

    Karolak-Wojciechowska, J.; Czylkowski, R.; Karczmarzyk, Z.; Paluchowska, M. H.; Rys, B.; Szneler, E.; Mokrosz, M. J.

    2002-06-01

    The X-ray crystal structures of series of 1-aryl-1,4-dihydro-3(2H)-isoquinolinones (1-7) have been determined. Lactame heterocyclic ring possesses more or less deformed boat conformation in all examined structures. The aryl substituent adopts the equatorial position in the structures 1-3 and the axial one in 5-7. In the structure of 4, due to extremely flattened heterocyclic ring, aryl substituent location can be named as bisectional. In all solved structures the molecules are joined into the dimers via two N-H⋯O hydrogen bonds. At the same time, 1H NMR studies in DMSO-d6 solutions were accomplished and profound analysis of 2J, 3J, and 5J coupling constants have shown that in isoquinolinone system the heterocyclic ring adopts the boat conformation in all investigated compounds. The stereochemical orientations of the phenyl ring at C1 do not depend on the nature of the substituent but, exclusively, on the mode of substitution. However, three forms of undulated laktam heterocyclic ring conformation in respect of 1-aryl substituent positions were confirmed by calculation (conformational analysis).

  9. Synthesis of benzannelated sultams by intramolecular Pd-catalyzed arylation of tertiary sulfonamides

    Directory of Open Access Journals (Sweden)

    Valentin A. Rassadin

    2017-09-01

    Full Text Available A new and efficient approach to five- and six-membered benzannelated sultams by intramolecular C-arylation of tertiary 1-(methoxycarbonylmethanesulfonamides under palladium catalysis is described. In case of the α-toluenesulfonamide derivative, an unexpected formation of a 2,3-diarylindole was observed under the same conditions.

  10. Synthesis of benzannelated sultams by intramolecular Pd-catalyzed arylation of tertiary sulfonamides.

    Science.gov (United States)

    Rassadin, Valentin A; Scholz, Mirko; Klochkova, Anastasiia A; de Meijere, Armin; Sokolov, Victor V

    2017-01-01

    A new and efficient approach to five- and six-membered benzannelated sultams by intramolecular C -arylation of tertiary 1-(methoxycarbonyl)methanesulfonamides under palladium catalysis is described. In case of the α-toluenesulfonamide derivative, an unexpected formation of a 2,3-diarylindole was observed under the same conditions.

  11. 2-ARYL-6,8-DIBROMO-2,3-DIHYDROQUINAZOLIN-4(1H)

    African Journals Online (AJOL)

    Preferred Customer

    in synthesis because of their rich biological activities and excellent pharmacological properties [1-. 5]. These compounds are ... We herein describe the synthesis of the 2-aryl-6,8-dibromo-2,3-dihydroquinazolin-. 4(1H)-ones and sequential ... 3(4H)-ones with aqueous ammonia under reflux [22]. (i). NH2. O. NH2. NH2. O.

  12. Brønsted acid-surfactant (BAS catalysed cyclotrimerization of aryl methyl ketone

    Directory of Open Access Journals (Sweden)

    Kiran Phatangare

    2012-07-01

    Full Text Available A brønsted acid-surfactant catalysed and simple, mild, metal catalyst free and chemo-selective method has been developed for synthesis of 1, 3, 5-triaryl benzenes from aryl methyl ketones. The advantages of this protocol subsume green and sustainable reaction medium, mild reaction conditions, easy product recovery and its good yields.

  13. SAR studies of 6-aryl-1,3-dihydrobenzimidazol-2-ones as progesterone receptor antagonists.

    Science.gov (United States)

    Terefenko, Eugene A; Kern, Jeffrey; Fensome, Andrew; Wrobel, Jay; Zhu, Yuan; Cohen, Jeffrey; Winneker, Richard; Zhang, Zhiming; Zhang, Puwen

    2005-08-01

    We have previously reported that the aryl substituted benzimidazolones, benzoxazinones, and oxindoles (e.g., 1-3) are progesterone receptor (PR) antagonists and have recently disclosed that the nature of 5- and 6-aryl moieties played a critical role in PR functional activity in the oxindole and benzoxazinone templates. For example, replacing the phenyl group of PR antagonists 2 and 3 with a 5'-cyanopyrrol-2'-yl moiety switched their functional activity to PR agonist activity (2a and 3a). These findings prompted us to examine if there is a similar effect of the 6-aryl moieties on the PR functional activity for the benzimidazolone template. Numerous analogs, such as 5, showed potent PR antagonist activity with about a 10-fold increase in potency as compared to those reported earlier in the same series. More interestingly, pyrrole-containing benzimidazolones 24-27 remained as PR antagonists in contrast to the PR agonist activity switch for oxindole and benzoxazinone scaffolds when a 5'-cyanopyrrol-2'-yl group was installed as a pendant aryl group.

  14. Flax fabric reinforced arylated soy protein composites: A brittle-matrix behaviour

    CSIR Research Space (South Africa)

    Kumar, R

    2012-05-01

    Full Text Available Biocomposites were successfully prepared by the reinforcement of soy protein isolate (SPI) with different weight fractions of woven flax fabric. The flax-fabric-reinforced SPI-based composites were then arylated with 2,2-diphenyl-2-hydroxyethanoic...

  15. Synthesis of acyl carbamates via four component Pd-catalyzed carbonylative coupling of aryl halides, potassium cyanate, and alcohols.

    Science.gov (United States)

    Yin, Hongfei; de Almeida, Angelina M; de Almeida, Mauro V; Lindhardt, Anders T; Skrydstrup, Troels

    2015-03-06

    A simple and mild method is demonstrated for assembling acyl carbamates through a base-free four-component Pd-catalyzed carbonylation of aryl halides in the presence of potassium cyanate and alcohols in a two-chamber system. This approach produces a wide range of aryl acyl carbamates in good to excellent yields from the corresponding aryl bromides or iodides with near-stoichiometric carbon monoxide. In addition, the method can be extended to the synthesis of primary amides thereby expanding the usefulness of cyanate as an ammonia equivalent.

  16. Iridium(iii)-catalyzed regioselective direct arylation of sp(2) C-H bonds with diaryliodonium salts.

    Science.gov (United States)

    Gao, Pan; Liu, Li; Shi, Zhuangzhi; Yuan, Yu

    2016-08-07

    A regioselective direct arylation of arenes and olefins at the ortho position is reported. The key to the high selectivity is the appropriate choice of diaryliodonium salts as the arylating reagent in the presence of a cationic iridium(iii) catalyst. The coordination of the metal with an oxygen atom or a nitrogen atom and subsequent C-H activation allows for direct arylation with coupling partners. This reaction proceeds under mild reaction conditions and with a high tolerance of various functional groups including many halide functional groups.

  17. Merging Photoredox and Nickel Catalysis: The Direct Synthesis of Ketones by the Decarboxylative Arylation of α-Oxo Acids.

    Science.gov (United States)

    Chu, Lingling; Lipshultz, Jeffrey M; MacMillan, David W C

    2015-06-26

    The direct decarboxylative arylation of α-oxo acids has been achieved by synergistic visible-light-mediated photoredox and nickel catalysis. This method offers rapid entry to aryl and alkyl ketone architectures from simple α-oxo acid precursors via an acyl radical intermediate. Significant substrate scope is observed with respect to both the oxo acid and arene coupling partners. This mild decarboxylative arylation can also be utilized to efficiently access medicinal agents, as demonstrated by the rapid synthesis of fenofibrate. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Structure, cytotoxic activity and mechanism of protoilludane sesquiterpene aryl esters from the mycelium of Armillaria mellea.

    Science.gov (United States)

    Li, Zhijin; Wang, Yunchao; Jiang, Bin; Li, Wenliang; Zheng, Lihua; Yang, Xiaoguang; Bao, Yongli; Sun, Luguo; Huang, Yanxin; Li, Yuxin

    2016-05-26

    Armillaria mellea (Vahl. ex. Fr.) Karst is an important traditional Chinese medicine used in dispelling wind and removing obstruction in the meridians, and strengthening tendons and bones. Armillaria mellea has been recorded in the book Caobenshiyi which was written by ancestor for the function of suppressing hyderactive liver for calming endogenous wind medicine. The aim of this study is to investigate the cytotoxic activity for liver cell lines (normal and cancerous) of protoilludane sesquiterpene aryl esters from the mycelium of A. mellea. A systemic fractionation of the mycelium extracts of A. mellea and relative activity mechanisms were studied. Two new protoilludane sesquiterpene aryl esters named 5'-methoxy-armillasin (1) and 5-hydroxyl-armillarivin (2) were isolated. In addition, eight known protoilludane sesquiterpene aryl esters armillaridin (3), armillartin (4), armillarin (5), melleolide B (6), armillarilin (7), armillasin (8), armillarigin (9) and melleolide (10) were also isolated from the mycelium of A. mellea. The relative configurations of the two new compounds were confirmed by NOESY spectra. Among ten protoilludane sesquiterpene aryl esters, compounds 2, 3, 4, 7, 8, 9 and 10 were active constituents with highly cytotoxic activity against HepG2 cells (4.95-37.65μg/mL). We reported here for the time, that compound 10 (melleolide) showed anti-tumor ability on hepatoma cell. The relative mechanism was assessed on HepG2 cells. Among all the ten protoilludane sesquiterpene aryl esters, melleolide (10) showed the best cytotoxic activity for HepG2 cells (4.95μg/mL) and lower activity for L02 cells (16.05μg/mL). Mechanism study showed that melleolide decreased the viability of the cancer cells with varying levels of cleaved-caspase 3, caspase 8, caspase 9, Bax and Ki67 expression. On the other hand, melleolide induced HepG2 cell cycle arrest at the G2/M phase. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. A New Look at Trigger Point Injections

    OpenAIRE

    Wong, Clara S. M.; Wong, Steven H. S.

    2012-01-01

    Trigger point injections are commonly practised pain interventional techniques. However, there is still lack of objective diagnostic criteria for trigger points. The mechanisms of action of trigger point injection remain obscure and its efficacy remains heterogeneous. The advent of ultrasound technology in the noninvasive real-time imaging of soft tissues sheds new light on visualization of trigger points, explaining the effect of trigger point injection by blockade of peripheral nerves, and ...

  20. A new look at trigger point injections.

    Science.gov (United States)

    Wong, Clara S M; Wong, Steven H S

    2012-01-01

    Trigger point injections are commonly practised pain interventional techniques. However, there is still lack of objective diagnostic criteria for trigger points. The mechanisms of action of trigger point injection remain obscure and its efficacy remains heterogeneous. The advent of ultrasound technology in the noninvasive real-time imaging of soft tissues sheds new light on visualization of trigger points, explaining the effect of trigger point injection by blockade of peripheral nerves, and minimizing the complications of blind injection.

  1. Etiology of myofascial trigger points

    NARCIS (Netherlands)

    Bron, C.; Dommerholt, J.D.

    2012-01-01

    Myofascial pain syndrome (MPS) is described as the sensory, motor, and autonomic symptoms caused by myofascial trigger points (TrPs). Knowing the potential causes of TrPs is important to prevent their development and recurrence, but also to inactivate and eliminate existing TrPs. There is general

  2. Syngas Upgrading to Hydrocarbon Fuels Technology Pathway

    Energy Technology Data Exchange (ETDEWEB)

    Talmadge, M.; Biddy, M.; Dutta, A.; Jones, S.; Meyer, A.

    2013-03-01

    This technology pathway case investigates the upgrading of woody biomass derived synthesis gas (syngas) to hydrocarbon biofuels. While this specific discussion focuses on the conversion of syngas via a methanol intermediate to hydrocarbon blendstocks, there are a number of alternative conversion routes for production of hydrocarbons through a wide array of intermediates from syngas. Future work will also consider the variations to this pathway to determine the most economically viable and lowest risk conversion route. Technical barriers and key research needs have been identified that should be pursued for the syngas-to-hydrocarbon pathway to be competitive with petroleum-derived gasoline-, diesel- and jet-range hydrocarbon blendstocks.

  3. Methods for deactivating copper in hydrocarbon fluids

    Energy Technology Data Exchange (ETDEWEB)

    Roling, P.V.; Niu, J.H.Y.; Reid, D.K.

    1988-06-07

    This patent describes a method of inhibiting the formation of free radicals in a hydrocarbon medium by deactivating a metallic species selected from the group consisting of Cu, Fe, CO, Ni, V, Cr, and Mn contained in the hydrocarbon medium, wherein in the absence of the deactivating the metallic species would initiate formation of free radicals in the hydrocarbon medium in turn leading to decomposition of the hydrocarbon medium. The method comprises inhibiting the formation of free radicals by adding to the hydrocarbon medium, which already contains the metal species, an effective amount to deactivate the metallic species of an effective Mannich product formed by reaction of reactants (A), (B), and (C).

  4. Limitations of the toxic equivalency factor (TEF) approach for risk assessment of halogenated aromatic hydrocarbons

    Energy Technology Data Exchange (ETDEWEB)

    Safe, S. [Texas A and M Univ., College Station, TX (United States). Dept. of Veterinary Physiology and Pharmacology

    1995-12-31

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related halogenated aromatic hydrocarbons (HAHs) are present as complex mixtures of polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and biphenyls (PCBs) in most environmental matrices. Risk management of these mixtures utilize the toxic equivalency factor (TEF) approach in which the TCDD (dioxin) or toxic equivalents of a mixture is a summation of the congener concentration (Ci) times TEF{sub i} (potency relative to TCDD) where. TEQ{sub mixture} = {Sigma}[Cil] {times} TEF{sub i}. TEQs are determined only for those HAHs which are aryl hydrocarbon (Ah) receptor agonists and this approach assumes that the toxic or biochemical effects of individual compounds in a mixture are additive. Several in vivo and in vitro laboratory and field studies with different HAH mixtures have been utilized to validate the TEF approach. For some responses, the calculated toxicities of PCDD/PCDF and PCB mixtures predict the observed toxic potencies. However, for fetal cleft palate and immunotoxicity in mice, nonadditive (antagonistic) responses are observed using complex PCB mixtures or binary mixtures containing an Ah receptor agonist with 2,2{prime},4,4{prime},5,5{prime}-hexachlorobiphenyl (PCB153). The potential interactive effects of PCBs and other dietary Ah receptor antagonist suggest that the TEF approach for risk management of HAHs requires further refinement and should be used selectively.

  5. Trigger electronics for the ALICE PHOS detector

    CERN Document Server

    Müller, H; Musa, L; Yin, Z; Röhrich, D; Skaali, B; Sibiryak, Yu; Budnikov, D L

    2004-01-01

    The Photon Spectrometer of ALICE consists of 5 identical modules of 56 multiplied by 64 PWO crystals with a total of 100 degree azimuthal coverage of the barrel. The electronics required for implementing both the L0 trigger for high luminosity p-p physics and the L1 trigger for high p//T Pb+Pb physics has been studied. A full integration of the trigger logic into the detector's enclosure is based on analog transmission of fast trigger sums between stacks of front-end boards and trigger-router units. The latter contain 112 digitizer channels of 10bit, which are mapped into a single FPGA per trigger unit, covering areas of 24 multiplied by 16 crystals. The running modes allow for Level-0 trigger at 800ns and Level-1 at 6200ns trigger latencies. The design and status of the PHOS trigger electronics are outlined.

  6. Hydrocarbon Rocket Technology Impact Forecasting

    Science.gov (United States)

    Stuber, Eric; Prasadh, Nishant; Edwards, Stephen; Mavris, Dimitri N.

    2012-01-01

    Ever since the Apollo program ended, the development of launch propulsion systems in the US has fallen drastically, with only two new booster engine developments, the SSME and the RS-68, occurring in the past few decades.1 In recent years, however, there has been an increased interest in pursuing more effective launch propulsion technologies in the U.S., exemplified by the NASA Office of the Chief Technologist s inclusion of Launch Propulsion Systems as the first technological area in the Space Technology Roadmaps2. One area of particular interest to both government agencies and commercial entities has been the development of hydrocarbon engines; NASA and the Air Force Research Lab3 have expressed interest in the use of hydrocarbon fuels for their respective SLS Booster and Reusable Booster System concepts, and two major commercially-developed launch vehicles SpaceX s Falcon 9 and Orbital Sciences Antares feature engines that use RP-1 kerosene fuel. Compared to engines powered by liquid hydrogen, hydrocarbon-fueled engines have a greater propellant density (usually resulting in a lighter overall engine), produce greater propulsive force, possess easier fuel handling and loading, and for reusable vehicle concepts can provide a shorter turnaround time between launches. These benefits suggest that a hydrocarbon-fueled launch vehicle would allow for a cheap and frequent means of access to space.1 However, the time and money required for the development of a new engine still presents a major challenge. Long and costly design, development, testing and evaluation (DDT&E) programs underscore the importance of identifying critical technologies and prioritizing investment efforts. Trade studies must be performed on engine concepts examining the affordability, operability, and reliability of each concept, and quantifying the impacts of proposed technologies. These studies can be performed through use of the Technology Impact Forecasting (TIF) method. The Technology Impact

  7. Cooperative effect of silver in copper-catalyzed trifluoromethylation of aryl iodides using Me3SiCF3

    KAUST Repository

    Weng, Zhiqiang

    2011-06-13

    An effective model of cooperative effect of silver for the coppercatalyzed trifluoromethylation of activated and unactivated aryl iodides to trifluoromethylated arenes using Me3SiCF3 was achieved with a broad substrate scope. © 2011 American Chemical Society.

  8. Arynes, diaryliodonium salts and azine N-oxides in transition metal-free electrophilic N-arylation

    Science.gov (United States)

    Bugaenko, D. I.; Karchava, A. V.; Yurovskaya, M. A.

    2018-03-01

    The main approach to the synthesis of aromatic and heteroaromatic amines is based on palladium- and copper-catalyzed N-arylation reactions. Although these methods are highly efficient and provide extensive opportunities for the synthesis of (het)arylamines with various structures and properties, they have some limitations related to the catalysts used and reaction conditions. This review addresses alternative approaches to N-(het)arylation that have been extensively developed in the past decade and are based on the use of arynes, diaryliodonium salts and azine N-oxides as electrophilic (het)arylating agents. Because of mild reaction conditions and no need for catalysts and strong bases, these N-(het)arylation methods are attractive for various synthetic applications and open up new possibilities for the preparation of valuable organic compounds inaccessible via traditional catalytic methods. The attention is focussed on publications of the last decade. The bibliography includes 112 references.

  9. Silylformylation - Fluoride-assisted aryl migration of acetylenic derivatives in a versatile approach to the synthesis of polyfunctionalised compounds

    NARCIS (Netherlands)

    Aronica, LA; Raffa, P; Valentini, G; Caporusso, AM; Salvadori, P

    2006-01-01

    Polyfunctionalised aldehydes and dihydropyrans are prepared from easily available functionalised 1-alkynes through a two-step silylformylation/aryl migration sequence. The silylformylation process is performed under mild experimental conditions and affords the corresponding beta-silylalkenals in

  10. Catalytic method for synthesizing hydrocarbons

    Science.gov (United States)

    Sapienza, R.S.; Sansone, M.J.; Slegeir, W.A.R.

    A method for synthesizing hydrocarbons from carbon monoxide and hydrogen by contacting said gases with a slurry of a catalyst composed of palladium or platinum and cobalt supported on a solid phase is disclosed. The catalyst is prepared by heating a heterogeneous component of the palladium or platinum deposited on the solid support in a solution of cobalt carbonyl or precursors thereof. The catalyst exhibits excellent activity, stability in air, and produces highly desirable product fractions even with dilute gaseous reactants.

  11. Deep desulfurization of hydrocarbon fuels

    Science.gov (United States)

    Song, Chunshan [State College, PA; Ma, Xiaoliang [State College, PA; Sprague, Michael J [Calgary, CA; Subramani, Velu [State College, PA

    2012-04-17

    The invention relates to processes for reducing the sulfur content in hydrocarbon fuels such as gasoline, diesel fuel and jet fuel. The invention provides a method and materials for producing ultra low sulfur content transportation fuels for motor vehicles as well as for applications such as fuel cells. The materials and method of the invention may be used at ambient or elevated temperatures and at ambient or elevated pressures without the need for hydrogen.

  12. Abnormal pressure in hydrocarbon environments

    Science.gov (United States)

    Law, B.E.; Spencer, C.W.

    1998-01-01

    Abnormal pressures, pressures above or below hydrostatic pressures, occur on all continents in a wide range of geological conditions. According to a survey of published literature on abnormal pressures, compaction disequilibrium and hydrocarbon generation are the two most commonly cited causes of abnormally high pressure in petroleum provinces. In young (Tertiary) deltaic sequences, compaction disequilibrium is the dominant cause of abnormal pressure. In older (pre-Tertiary) lithified rocks, hydrocarbon generation, aquathermal expansion, and tectonics are most often cited as the causes of abnormal pressure. The association of abnormal pressures with hydrocarbon accumulations is statistically significant. Within abnormally pressured reservoirs, empirical evidence indicates that the bulk of economically recoverable oil and gas occurs in reservoirs with pressure gradients less than 0.75 psi/ft (17.4 kPa/m) and there is very little production potential from reservoirs that exceed 0.85 psi/ft (19.6 kPa/m). Abnormally pressured rocks are also commonly associated with unconventional gas accumulations where the pressuring phase is gas of either a thermal or microbial origin. In underpressured, thermally mature rocks, the affected reservoirs have most often experienced a significant cooling history and probably evolved from an originally overpressured system.

  13. Source rock hydrocarbons. Present status

    International Nuclear Information System (INIS)

    Vially, R.; Maisonnier, G.; Rouaud, T.

    2013-01-01

    This report first presents the characteristics of conventional oil and gas system, and the classification of liquid and gaseous non conventional hydrocarbons, with the peculiar case of coal-bed methane. The authors then describe how source rock hydrocarbons are produced: production of shale oils and gases (horizontal drilling, hydraulic fracturing, exploitation) and of coal-bed methane and coal mine methane. In the next part, they address and discuss the environmental impact of source rock hydrocarbon production: installation footprint, water resource management, drilling fluids, fracturing fluids composition, toxicity and recycling, air pollution, induced seismicity, pollutions from other exploitation and production activities. They propose an overview of the exploitation and production of source rock gas, coal-bed gas and other non conventional gases in the world. They describe the current development and discuss their economic impacts: world oil context and trends in the USA, in Canada and other countries, impacts on the North American market, on the world oil industry, on refining industries, on the world oil balance. They analyse the economic impacts of non conventional gases: development potential, stakes for the world gas trade, consequence for gas prices, development opportunities for oil companies and for the transport sector, impact on CO 2 emissions, macro-economic impact in the case of the USA

  14. Triggers and Their Influence on Health Behaviors.

    Science.gov (United States)

    Gipson, Christine S

    2017-05-01

    This article provides a conceptual definition of the concept trigger within the context of health behaviors and applies it to the highly significant health issue of obesity. Healthy behaviors are essential to life and happiness, but they do not just happen. They are triggered, and an inner drive keeps them alive. To help patients gain and retain optimal health, nurses must understand the triggers of healthy behaviors. Walker and Avant's (2011) method of concept analysis is used as the basis for defining the concept of trigger. The antecedents, defining attributes, and consequences of trigger are identified. Findings suggest that nurses can play a role in triggering health behavior change through simple motivational efforts.

  15. A unified approach for the synthesis of symmetrical and unsymmetrical dibenzyl ethers from aryl aldehydes through reductive etherification

    Directory of Open Access Journals (Sweden)

    J. Sembian Ruso

    2016-05-01

    Full Text Available In this paper, we describe a simple and convenient conversion of aryl aldehydes to symmetrical dibenzyl ethers through reductive etherification. Similarly, unsymmetrical dibenzyl ether was obtained from aryl aldehyde and TES-protected benzyl alcohol. Triethyl silane with catalytic amount of InCl3 was found to be an efficient condition for the reductive etherification. Moreover, it exhibits remarkable functional group compatibility with yield ranging from good to excellent.

  16. Design and stereoselective synthesis of a C-aryl furanoside as a conformationally constrained CHIR-090 analogue

    DEFF Research Database (Denmark)

    Oddo, Alberto; Holl, Ralph

    2012-01-01

    The UDP-3-O-[(R)-3-hydroxymyristoyl]-N-acetylglucosamine deacetylase (LpxC) is a promising target for the development of novel antibiotic substances against multidrug-resistant Gram-negative bacteria. The C-aryl glycoside 3 was designed as conformationally constrained analogue of the potent LpxC-......, and esterification. A Sonogashira reaction of the aryl iodide 11 led to the alkyne 17 which was transformed with H(2)NOH into the hydroxamic acid 3....

  17. Muon Trigger for Mobile Phones

    Science.gov (United States)

    Borisyak, M.; Usvyatsov, M.; Mulhearn, M.; Shimmin, C.; Ustyuzhanin, A.

    2017-10-01

    The CRAYFIS experiment proposes to use privately owned mobile phones as a ground detector array for Ultra High Energy Cosmic Rays. Upon interacting with Earth’s atmosphere, these events produce extensive particle showers which can be detected by cameras on mobile phones. A typical shower contains minimally-ionizing particles such as muons. As these particles interact with CMOS image sensors, they may leave tracks of faintly-activated pixels that are sometimes hard to distinguish from random detector noise. Triggers that rely on the presence of very bright pixels within an image frame are not efficient in this case. We present a trigger algorithm based on Convolutional Neural Networks which selects images containing such tracks and are evaluated in a lazy manner: the response of each successive layer is computed only if activation of the current layer satisfies a continuation criterion. Usage of neural networks increases the sensitivity considerably comparable with image thresholding, while the lazy evaluation allows for execution of the trigger under the limited computational power of mobile phones.

  18. ATLAS Level-1 Topological Trigger

    CERN Document Server

    Zheng, Daniel; The ATLAS collaboration

    2018-01-01

    The ATLAS experiment has introduced and recently commissioned a completely new hardware sub-system of its first-level trigger: the topological processor (L1Topo). L1Topo consist of two AdvancedTCA blades mounting state-of-the-art FPGA processors, providing high input bandwidth (up to 4 Gb/s) and low latency data processing (200 ns). L1Topo is able to select collision events by applying kinematic and topological requirements on candidate objects (energy clusters, jets, and muons) measured by calorimeters and muon sub-detectors. Results from data recorded using the L1Topo trigger will be presented. These results demonstrate a significantly improved background event rejection, thus allowing for a rate reduction without efficiency loss. This improvement has been shown for several physics processes leading to low-pT leptons, including H->tau tau and J/Psi->mu mu. In addition to describing the L1Topo trigger system, we will discuss the use of an accurate L1Topo simulation as a powerful tool to validate and optimize...

  19. Industrial accidents triggered by lightning.

    Science.gov (United States)

    Renni, Elisabetta; Krausmann, Elisabeth; Cozzani, Valerio

    2010-12-15

    Natural disasters can cause major accidents in chemical facilities where they can lead to the release of hazardous materials which in turn can result in fires, explosions or toxic dispersion. Lightning strikes are the most frequent cause of major accidents triggered by natural events. In order to contribute towards the development of a quantitative approach for assessing lightning risk at industrial facilities, lightning-triggered accident case histories were retrieved from the major industrial accident databases and analysed to extract information on types of vulnerable equipment, failure dynamics and damage states, as well as on the final consequences of the event. The most vulnerable category of equipment is storage tanks. Lightning damage is incurred by immediate ignition, electrical and electronic systems failure or structural damage with subsequent release. Toxic releases and tank fires tend to be the most common scenarios associated with lightning strikes. Oil, diesel and gasoline are the substances most frequently released during lightning-triggered Natech accidents. Copyright © 2010 Elsevier B.V. All rights reserved.

  20. Stimulus conflict triggers behavioral avoidance.

    Science.gov (United States)

    Dignath, David; Eder, Andreas B

    2015-12-01

    According to a recent extension of the conflict-monitoring theory, conflict between two competing response tendencies is registered as an aversive event and triggers a motivation to avoid the source of conflict. In the present study, we tested this assumption. Over five experiments, we examined whether conflict is associated with an avoidance motivation and whether stimulus conflict or response conflict triggers an avoidance tendency. Participants first performed a color Stroop task. In a subsequent motivation test, participants responded to Stroop stimuli with approach- and avoidance-related lever movements. These results showed that Stroop-conflict stimuli increased the frequency of avoidance responses in a free-choice motivation test, and also increased the speed of avoidance relative to approach responses in a forced-choice test. High and low proportions of response conflict in the Stroop task had no effect on avoidance in the motivation test. Avoidance of conflict was, however, obtained even with new conflict stimuli that had not been presented before in a Stroop task, and when the Stroop task was replaced with an unrelated filler task. Taken together, these results suggest that stimulus conflict is sufficient to trigger avoidance.